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df84bb9806bf12946adb5ac5f2f094f885615155 | wikidoc | Glucose | Glucose
# Overview
Glucose (Glc), a monosaccharide (or simple sugar), is an important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate. Glucose is one of the main products of photosynthesis and starts cellular respiration in both prokaryotes and eukaryotes. The name comes from the Greek word glykys (γλυκύς), which means "sweet", plus the suffix "-ose" which denotes a sugar.
Two stereoisomers of the aldohexose sugars are known as glucose, only one of which (D-glucose) is biologically active. This form (D-glucose) is often referred to as dextrose monohydrate, or, especially in the food industry, simply dextrose (from dextrorotatory glucose). This article deals with the D-form of glucose. The mirror-image of the molecule, L-glucose, cannot be metabolized by cells in the biochemical process known as glycolysis.
Glucose is commonly available in the form of a white substance or as a solid crystal. It can also be commonly found as an aqueous solution.
# Structure
Glucose (C6H12O6) contains six carbon atoms one of which is part of an aldehyde group and is therefore referred to as an aldohexose. In solution, the glucose molecule can exist in an open-chain (acyclic) and ring (cyclic) form (in equilibrium), the latter being the result of a covalent bond between the aldehyde C atom and the C-5 hydroxyl group to form a six-membered cyclic hemiacetal. At pH 7 the cyclic form is predominant. In the solid phase, glucose assumes the cyclic form. As the ring contains five carbon atoms and one oxygen atom, which resembles the structure of pyran, the cyclic form of glucose is also referred to as glucopyranose. In this ring, each carbon is linked to a hydroxyl side group with the exception of the fifth atom, which links to a sixth carbon atom outside the ring, forming a CH2OH group.
## Isomers
Aldohexose sugars have 4 chiral centers giving 24 = 16 stereoisomers. These are split into two groups, L and D, with 8 sugars in each. Glucose is one of these sugars, and L and D-glucose are two of the stereoisomers. Only 7 of these are found in living organisms, of which D-glucose (Glu), D-galactose (Gal) and D-mannose (Man) are the most important. These eight isomers (including glucose itself) are all diastereoisomers in relation to each other and all belong to the D-series.
An additional asymmetric center at C-1 (called the anomeric carbon atom) is created when glucose cyclizes and two ring structures, called anomers are formed — α-glucose and β-glucose. These anomers differ structurally with respect to the relative positioning of their hydroxyl group linked to C-1 and the group at C-6, which is termed the reference carbon. When D-glucose is drawn as a Haworth projection or in the standard chair conformation, the designation α means that the hydroxyl group attached to C-1 is positioned trans to the -CH2OH group at C-5, while β means it is cis. Another popular method of distinguishing α from β is by observing whether the C-1 hydroxyl is below or above the plane of the ring, respectively, but this method is an inaccurate definition and may fail if the glucose ring is drawn upside down or in an alternative chair conformation. The α and β forms interconvert over a timescale of hours in aqueous solution, to a final stable ratio of α:β 36:64, in a process called mutarotation.
- The Fischer projection of the chain form of D-glucose
- The chain form of D-glucose
- α-D-glucopyranose
- β-D-glucopyranose
- Chain form: ball-and-stick model
- Chain form: space-filling model
- α-D-glucopyranose
- β-D-glucopyranose
## Rotamers
Within the cyclic form of glucose, rotation may occur around the O6-C6-C5-O5 torsion angle, termed the ω-angle, to form three rotamer conformations as shown in the diagram below. Referring to the orientations of the ω-angle and the O6-C6-C5-C4 angle the three stable staggered rotamer conformations are termed gauche-gauche (gg), gauche-trans (gt) and trans-gauche (tg). For methyl α-D-glucopyranose at equilibrium the ratio of molecules in each rotamer conformation is reported as 57:38:5 gg:gt:tg.
This tendency for the ω-angle to prefer to adopt a gauche conformation is attributed to the gauche effect.
# Production
## Natural
- Glucose is one of the products of photosynthesis in plants and some prokaryotes.
- In animals and fungi, glucose is the result of the breakdown of glycogen, a process known as glycogenolysis. In plants the breakdown substrate is starch.
- In animals, glucose is synthesized in the liver and kidneys from non-carbohydrate intermediates, such as pyruvate and glycerol, by a process known as gluconeogenesis.
## Commercial
Glucose is produced commercially via the enzymatic hydrolysis of starch. Many crops can be used as the source of starch. Maize, rice, wheat, potato, cassava, arrowroot, and sago are all used in various parts of the world. In the United States, cornstarch (from maize) is used almost exclusively.
This enzymatic process has two stages. Over the course of 1-2 hours near 100 °C, enzymes hydrolyze starch into smaller carbohydrates containing on average 5-10 glucose units each. Some variations on this process briefly heat the starch mixture to 130 °C or hotter one or more times. This heat treatment improves the solubility of starch in water, but deactivates the enzyme, and fresh enzyme must be added to the mixture after each heating.
In the second step, known as "saccharification", the partially hydrolyzed starch is completely hydrolyzed to glucose using the glucoamylase enzyme from the fungus Aspergillus niger. Typical reaction conditions are pH 4.0–4.5, 60 °C, and a carbohydrate concentration of 30–35% by weight. Under these conditions, starch can be converted to glucose at 96% yield after 1–4 days. Still higher yields can be obtained using more dilute solutions, but this approach requires larger reactors and processing a greater volume of water, and is not generally economical. The resulting glucose solution is then purified by filtration and concentrated in a multiple-effect evaporator. Solid D-glucose is then produced by repeated crystallizations.
- Glucose
- Glucose tablets
Glucose tablets
# Function
We can speculate on the reasons why glucose, and not another monosaccharide such as fructose (Fru), is so widely used in evolution, the ecosystem, and metabolism. Glucose can form from formaldehyde under abiotic conditions, so it may well have been available to primitive biochemical systems. Probably more important to advanced life is the low tendency of glucose, by comparison to other hexose sugars, to non-specifically react with the amino groups of proteins. This reaction (glycation) reduces or destroys the function of many enzymes. The low rate of glycation is due to glucose's preference for the less reactive cyclic isomer. Nevertheless, many of the long-term complications of diabetes (e.g., blindness, kidney failure, and peripheral neuropathy) are probably due to the glycation of proteins or lipids. In contrast, enzyme-regulated addition of glucose to proteins by glycosylation is often essential to their function.
## As an energy source
Glucose is a ubiquitous fuel in biology. It is used as an energy source in most organisms, from bacteria to humans. Use of glucose may be by either aerobic or anaerobic respiration (fermentation). Carbohydrates are the human body's key source of energy, through aerobic respiration, providing approximately 3.75 kilocalories (16 kilojoules) of food energy per gram. Breakdown of carbohydrates (e.g. starch) yields mono- and disaccharides, most of which is glucose. Through glycolysis and later in the reactions of the Citric acid cycle (TCAC), glucose is oxidized to eventually form CO2 and water, yielding energy, mostly in the form of ATP. The insulin reaction, and other mechanisms, regulate the concentration of glucose in the blood. A high fasting blood sugar level is an indication of prediabetic and diabetic conditions.
Glucose is a primary source of energy for the brain, and hence its availability influences psychological processes. When glucose is low, psychological processes requiring mental effort (e.g., self-control) are impaired.
## Glucose in glycolysis
Use of glucose as an energy source in cells is via aerobic or anaerobic respiration. Both of these start with the early steps of the glycolysis metabolic pathway. The first step of this is the phosphorylation of glucose by hexokinase to prepare it for later breakdown to provide energy.
The major reason for the immediate phosphorylation of glucose by a hexokinase is to prevent diffusion out of the cell. The phosphorylation adds a charged phosphate group so the glucose 6-phosphate cannot easily cross the cell membrane. Irreversible first steps of a metabolic pathway are common for regulatory purposes.
## As a precursor
Glucose is critical in the production of proteins and in lipid metabolism. Also, in plants and most animals, it is a precursor for vitamin C (ascorbic acid) production. It is modified for use in these processes by the glycolysis pathway.
Glucose is used as a precursor for the synthesis of several important substances. starch solution Starch, cellulose, and glycogen ("animal starch") are common glucose polymers (polysaccharides). Lactose, the predominant sugar in milk, is a glucose-galactose disaccharide. In sucrose, another important disaccharide, glucose is joined to fructose. These synthesis processes also rely on the phosphorylation of glucose through the first step of glycolysis.
# Sources and absorption
All major dietary carbohydrates contain glucose, either as their only building block, as in starch and glycogen, or together with another monosaccharide, as in sucrose and lactose. In the lumen of the duodenum and small intestine, the oligo- and polysaccharides are broken down to monosaccharides by the pancreatic and intestinal glycosidases. Glucose is then transported across the apical membrane of the enterocytes by SLC5A1, and later across their basal membrane by SLC2A2. Some of the glucose goes directly toward fueling brain cells and erythrocytes, while the rest makes its way to the liver and muscles, where it is stored as glycogen, and to fat cells, where it can be used to power reactions which synthesize some fats. Glycogen is the body's auxiliary energy source, tapped and converted back into glucose when there is need for energy. | Glucose
Template:Chembox new
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Glucose (Glc), a monosaccharide (or simple sugar), is an important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate. Glucose is one of the main products of photosynthesis and starts cellular respiration in both prokaryotes and eukaryotes. The name comes from the Greek word glykys (γλυκύς), which means "sweet", plus the suffix "-ose" which denotes a sugar.
Two stereoisomers of the aldohexose sugars are known as glucose, only one of which (D-glucose) is biologically active. This form (D-glucose) is often referred to as dextrose monohydrate, or, especially in the food industry, simply dextrose (from dextrorotatory glucose[1]). This article deals with the D-form of glucose. The mirror-image of the molecule, L-glucose, cannot be metabolized by cells in the biochemical process known as glycolysis.
Glucose is commonly available in the form of a white substance or as a solid crystal. It can also be commonly found as an aqueous solution.
# Structure
Glucose (C6H12O6) contains six carbon atoms one of which is part of an aldehyde group and is therefore referred to as an aldohexose. In solution, the glucose molecule can exist in an open-chain (acyclic) and ring (cyclic) form (in equilibrium), the latter being the result of a covalent bond between the aldehyde C atom and the C-5 hydroxyl group to form a six-membered cyclic hemiacetal. At pH 7 the cyclic form is predominant. In the solid phase, glucose assumes the cyclic form. As the ring contains five carbon atoms and one oxygen atom, which resembles the structure of pyran, the cyclic form of glucose is also referred to as glucopyranose. In this ring, each carbon is linked to a hydroxyl side group with the exception of the fifth atom, which links to a sixth carbon atom outside the ring, forming a CH2OH group.
## Isomers
Aldohexose sugars have 4 chiral centers giving 24 = 16 stereoisomers. These are split into two groups, L and D, with 8 sugars in each. Glucose is one of these sugars, and L and D-glucose are two of the stereoisomers. Only 7 of these are found in living organisms, of which D-glucose (Glu), D-galactose (Gal) and D-mannose (Man) are the most important. These eight isomers (including glucose itself) are all diastereoisomers in relation to each other and all belong to the D-series.
An additional asymmetric center at C-1 (called the anomeric carbon atom) is created when glucose cyclizes and two ring structures, called anomers are formed — α-glucose and β-glucose. These anomers differ structurally with respect to the relative positioning of their hydroxyl group linked to C-1 and the group at C-6, which is termed the reference carbon. When D-glucose is drawn as a Haworth projection or in the standard chair conformation, the designation α means that the hydroxyl group attached to C-1 is positioned trans to the -CH2OH group at C-5, while β means it is cis. Another popular method of distinguishing α from β is by observing whether the C-1 hydroxyl is below or above the plane of the ring, respectively, but this method is an inaccurate definition and may fail if the glucose ring is drawn upside down or in an alternative chair conformation. The α and β forms interconvert over a timescale of hours in aqueous solution, to a final stable ratio of α:β 36:64, in a process called mutarotation.[2]
- The Fischer projection of the chain form of D-glucose
- The chain form of D-glucose
- α-D-glucopyranose
- β-D-glucopyranose
- Chain form: ball-and-stick model
- Chain form: space-filling model
- α-D-glucopyranose
- β-D-glucopyranose
## Rotamers
Within the cyclic form of glucose, rotation may occur around the O6-C6-C5-O5 torsion angle, termed the ω-angle, to form three rotamer conformations as shown in the diagram below. Referring to the orientations of the ω-angle and the O6-C6-C5-C4 angle the three stable staggered rotamer conformations are termed gauche-gauche (gg), gauche-trans (gt) and trans-gauche (tg). For methyl α-D-glucopyranose at equilibrium the ratio of molecules in each rotamer conformation is reported as 57:38:5 gg:gt:tg.[3]
This tendency for the ω-angle to prefer to adopt a gauche conformation is attributed to the gauche effect.
# Production
## Natural
- Glucose is one of the products of photosynthesis in plants and some prokaryotes.
- In animals and fungi, glucose is the result of the breakdown of glycogen, a process known as glycogenolysis. In plants the breakdown substrate is starch.
- In animals, glucose is synthesized in the liver and kidneys from non-carbohydrate intermediates, such as pyruvate and glycerol, by a process known as gluconeogenesis.
## Commercial
Glucose is produced commercially via the enzymatic hydrolysis of starch. Many crops can be used as the source of starch. Maize, rice, wheat, potato, cassava, arrowroot, and sago are all used in various parts of the world. In the United States, cornstarch (from maize) is used almost exclusively.
This enzymatic process has two stages. Over the course of 1-2 hours near 100 °C, enzymes hydrolyze starch into smaller carbohydrates containing on average 5-10 glucose units each. Some variations on this process briefly heat the starch mixture to 130 °C or hotter one or more times. This heat treatment improves the solubility of starch in water, but deactivates the enzyme, and fresh enzyme must be added to the mixture after each heating.
In the second step, known as "saccharification", the partially hydrolyzed starch is completely hydrolyzed to glucose using the glucoamylase enzyme from the fungus Aspergillus niger. Typical reaction conditions are pH 4.0–4.5, 60 °C, and a carbohydrate concentration of 30–35% by weight. Under these conditions, starch can be converted to glucose at 96% yield after 1–4 days. Still higher yields can be obtained using more dilute solutions, but this approach requires larger reactors and processing a greater volume of water, and is not generally economical. The resulting glucose solution is then purified by filtration and concentrated in a multiple-effect evaporator. Solid D-glucose is then produced by repeated crystallizations.
- Glucose
- Glucose tablets
Glucose tablets
# Function
We can speculate on the reasons why glucose, and not another monosaccharide such as fructose (Fru), is so widely used in evolution, the ecosystem, and metabolism. Glucose can form from formaldehyde under abiotic conditions, so it may well have been available to primitive biochemical systems. Probably more important to advanced life is the low tendency of glucose, by comparison to other hexose sugars, to non-specifically react with the amino groups of proteins. This reaction (glycation) reduces or destroys the function of many enzymes. The low rate of glycation is due to glucose's preference for the less reactive cyclic isomer. Nevertheless, many of the long-term complications of diabetes (e.g., blindness, kidney failure, and peripheral neuropathy) are probably due to the glycation of proteins or lipids. In contrast, enzyme-regulated addition of glucose to proteins by glycosylation is often essential to their function.
## As an energy source
Glucose is a ubiquitous fuel in biology. It is used as an energy source in most organisms, from bacteria to humans. Use of glucose may be by either aerobic or anaerobic respiration (fermentation). Carbohydrates are the human body's key source of energy, through aerobic respiration, providing approximately 3.75 kilocalories (16 kilojoules) of food energy per gram.[4] Breakdown of carbohydrates (e.g. starch) yields mono- and disaccharides, most of which is glucose. Through glycolysis and later in the reactions of the Citric acid cycle (TCAC), glucose is oxidized to eventually form CO2 and water, yielding energy, mostly in the form of ATP. The insulin reaction, and other mechanisms, regulate the concentration of glucose in the blood. A high fasting blood sugar level is an indication of prediabetic and diabetic conditions.
Glucose is a primary source of energy for the brain, and hence its availability influences psychological processes. When glucose is low, psychological processes requiring mental effort (e.g., self-control) are impaired.[5][6][7]
## Glucose in glycolysis
Use of glucose as an energy source in cells is via aerobic or anaerobic respiration. Both of these start with the early steps of the glycolysis metabolic pathway. The first step of this is the phosphorylation of glucose by hexokinase to prepare it for later breakdown to provide energy.
The major reason for the immediate phosphorylation of glucose by a hexokinase is to prevent diffusion out of the cell. The phosphorylation adds a charged phosphate group so the glucose 6-phosphate cannot easily cross the cell membrane. Irreversible first steps of a metabolic pathway are common for regulatory purposes.
## As a precursor
Glucose is critical in the production of proteins and in lipid metabolism. Also, in plants and most animals, it is a precursor for vitamin C (ascorbic acid) production. It is modified for use in these processes by the glycolysis pathway.
Glucose is used as a precursor for the synthesis of several important substances. starch solution Starch, cellulose, and glycogen ("animal starch") are common glucose polymers (polysaccharides). Lactose, the predominant sugar in milk, is a glucose-galactose disaccharide. In sucrose, another important disaccharide, glucose is joined to fructose. These synthesis processes also rely on the phosphorylation of glucose through the first step of glycolysis.
# Sources and absorption
All major dietary carbohydrates contain glucose, either as their only building block, as in starch and glycogen, or together with another monosaccharide, as in sucrose and lactose. In the lumen of the duodenum and small intestine, the oligo- and polysaccharides are broken down to monosaccharides by the pancreatic and intestinal glycosidases. Glucose is then transported across the apical membrane of the enterocytes by SLC5A1, and later across their basal membrane by SLC2A2.[8] Some of the glucose goes directly toward fueling brain cells and erythrocytes, while the rest makes its way to the liver and muscles, where it is stored as glycogen, and to fat cells, where it can be used to power reactions which synthesize some fats. Glycogen is the body's auxiliary energy source, tapped and converted back into glucose when there is need for energy. | https://www.wikidoc.org/index.php/D-glucose | |
044c29d16d0d8b2b59e7e8243ad73775f357093f | wikidoc | DC-SIGN | DC-SIGN
DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) also known as CD209 (Cluster of Differentiation 209) is a protein which in humans is encoded by the CD209 gene.
DC-SIGN is a C-type lectin receptor present on the surface of both macrophages and dendritic cells. DC-SIGN on macrophages recognises and binds to mannose type carbohydrates, a class of pathogen associated molecular patterns PAMPs commonly found on viruses, bacteria and fungi. This binding interaction activates phagocytosis. On myeloid and pre-plasmacytoid dendritic cells DC-SIGN mediates dendritic cell rolling interactions with blood endothelium and activation of CD4+ T cells, as well as recognition of pathogen haptens.
# Function
DC-SIGN is a C-type lectin and has a high affinity for the ICAM3 molecule. It binds various microorganisms by recognizing high-mannose-containing glycoproteins on their envelopes and especially functions as receptor for several viruses such as HIV and Hepatitis C. Binding to DC-SIGN can promote HIV and Hepatitis C virus to infect T-cell from dendritic cells. Thus binding to DC-SIGN is an essential process for HIV infection.
Besides functioning as an adhesion molecule, recent study has also shown that DC-SIGN can initiate innate immunity by modulating toll-like receptors, though the detailed mechanism is not yet known. DC-SIGN together with other C-type lectins is involved in recognition of tumors by dendritic cells. DC-SIGN is also a potential engineering target for dendritic cell based cancer vaccine.
# Role in HIV infection
This molecule is involved in the initial stages of the human immunodeficiency virus infection, as the HIV gp120 molecule causes co-internalization of the DC-SIGN molecule and HIV virus particle (virion). The dendritic cell then migrates to the cognate lymphoid organ, whereupon recycling of the DC-SIGN/HIV virion complex to the cell periphery facilitates HIV infection of CD4+ T cells by interaction between DC-SIGN and ICAM-3.
# Gene family
DC-SIGN/CD209 is an animal "C-lectin", a large and diverse family of proteins found in both prokaryotes and eukaryotes most of which are functional lectins, meaning they bind carbohydrate ligands, and whose ligand-binding affinity requires calcium (hence "C-lectin"). Among the animal C-lectins, a subfamily known as the ASGR (asialoglycoprotein receptors) group contains several sub-sub-families, many of which are important to innate immunity.
A cluster of genes in both humans and mice contains three related members of the "DC Receptor" class, so named because of their homology to DC-SIGN. Of these, CD23 is, however, not expressed on dendritic cells but is a characteristic surface molecule of B lymphocytes, and LSectin (CLEC4G) is expressed on the sinusoidal endothelium of the liver. The third gene group consists of multiple paralogues of CD209. Thus, both primates and mice have multiple paralogues of CD209 more closely related to each other within the species than to their orthologous counterparts in the other species. Higher primates have at least three DC-SIGN genes, DC-SIGN, DC-SIGNL1 and DC-SIGNL2, although not all three are present in every species; DC-SIGNL2 has not been detected in humans. Eight paralogous of DC-SIGN have been reported in the laboratory mouse strain C57BL/6; these go by the names DC-SIGN, DC-SIGNR2...DC-SIGNR8. DC-SIGNR6 is a pseudogene. The genes labeled "DC-SIGN" in the human and mouse are thus not unique orthologues, although they resemble each other functionally and by being expressed on dendritic cells. Other members of the mouse CD209 gene group are differentially expressed on different cell types. For example, DC-SIGNR1 is expressed largely on macrophages in the marginal zones of the spleen and in the medulla of lymph nodes. | DC-SIGN
DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) also known as CD209 (Cluster of Differentiation 209) is a protein which in humans is encoded by the CD209 gene.[1]
DC-SIGN is a C-type lectin receptor present on the surface of both macrophages and dendritic cells. DC-SIGN on macrophages recognises and binds to mannose type carbohydrates, a class of pathogen associated molecular patterns PAMPs commonly found on viruses, bacteria and fungi. This binding interaction activates phagocytosis.[2] On myeloid and pre-plasmacytoid dendritic cells DC-SIGN mediates dendritic cell rolling interactions with blood endothelium and activation of CD4+ T cells, as well as recognition of pathogen haptens.
# Function
DC-SIGN is a C-type lectin and has a high affinity for the ICAM3 molecule.[3] It binds various microorganisms by recognizing high-mannose-containing glycoproteins on their envelopes and especially functions as receptor for several viruses such as HIV and Hepatitis C.[4][5][6] Binding to DC-SIGN can promote HIV and Hepatitis C virus to infect T-cell from dendritic cells.[5][6] Thus binding to DC-SIGN is an essential process for HIV infection.[7]
Besides functioning as an adhesion molecule, recent study has also shown that DC-SIGN can initiate innate immunity by modulating toll-like receptors,[8] though the detailed mechanism is not yet known. DC-SIGN together with other C-type lectins is involved in recognition of tumors by dendritic cells. DC-SIGN is also a potential engineering target for dendritic cell based cancer vaccine.[9]
# Role in HIV infection
This molecule is involved in the initial stages of the human immunodeficiency virus infection, as the HIV gp120 molecule causes co-internalization of the DC-SIGN molecule and HIV virus particle (virion). The dendritic cell then migrates to the cognate lymphoid organ, whereupon recycling of the DC-SIGN/HIV virion complex to the cell periphery facilitates HIV infection of CD4+ T cells by interaction between DC-SIGN and ICAM-3.[10]
# Gene family
DC-SIGN/CD209 is an animal "C-lectin", a large and diverse family of proteins found in both prokaryotes and eukaryotes most of which are functional lectins, meaning they bind carbohydrate ligands, and whose ligand-binding affinity requires calcium (hence "C-lectin"). Among the animal C-lectins, a subfamily known as the ASGR (asialoglycoprotein receptors) group contains several sub-sub-families, many of which are important to innate immunity.
A cluster of genes in both humans and mice contains three related members of the "DC Receptor" class, so named because of their homology to DC-SIGN. Of these, CD23 is, however, not expressed on dendritic cells but is a characteristic surface molecule of B lymphocytes, and LSectin (CLEC4G) is expressed on the sinusoidal endothelium of the liver. The third gene group consists of multiple paralogues of CD209. Thus, both primates and mice have multiple paralogues of CD209 more closely related to each other within the species than to their orthologous counterparts in the other species. Higher primates have at least three DC-SIGN genes, DC-SIGN, DC-SIGNL1 and DC-SIGNL2, although not all three are present in every species; DC-SIGNL2 has not been detected in humans. Eight paralogous of DC-SIGN have been reported in the laboratory mouse strain C57BL/6; these go by the names DC-SIGN, DC-SIGNR2...DC-SIGNR8. DC-SIGNR6 is a pseudogene. The genes labeled "DC-SIGN" in the human and mouse are thus not unique orthologues, although they resemble each other functionally and by being expressed on dendritic cells. Other members of the mouse CD209 gene group are differentially expressed on different cell types. For example, DC-SIGNR1 is expressed largely on macrophages in the marginal zones of the spleen and in the medulla of lymph nodes.[11] | https://www.wikidoc.org/index.php/DC-SIGN | |
14e16dbe6241b049ce5b8e3b54aa1bfbc275fa51 | wikidoc | DCLRE1A | DCLRE1A
DNA cross-link repair 1A protein is a protein that in humans is encoded by the DCLRE1A gene.
DNA interstrand cross-links prevent strand separation, thereby physically blocking transcription, replication, and segregation of DNA. DCLRE1A is one of several evolutionarily conserved genes involved in repair of interstrand cross-links (Dronkert et al., 2000).
# Function
The protein DCLRE1A (DNA cross-link repair 1A) is also referred to as SNM1A (sensitive to nitrogen mustard 1A). DCLRE1A is a 5’ to 3’ exonuclease that forms a complex with the Cockayne syndrome B (CSB) protein. In this complex, CSB modulates the exonuclease activity of DCLRE1A and coordinates the efficient assembly of DCLRE1A to sites of DNA damage. In human cells, this complex is recruited to DNA inter-strand cross-links, a form of DNA damage. The complex then participates in the repair of the cross-linked DNA. DCLRE1A protein is thought to be recruited by CSB to facilitate cross-link unhooking following incision 5’ to the cross-link by another complex, the ERCC1/XPF nuclease complex. Failure of the DCLRE1A/CSB complex to carry out its repair function may contribute to the degenerative pathologies and premature aging features of Cockayne syndrome. | DCLRE1A
DNA cross-link repair 1A protein is a protein that in humans is encoded by the DCLRE1A gene.[1][2][3]
DNA interstrand cross-links prevent strand separation, thereby physically blocking transcription, replication, and segregation of DNA. DCLRE1A is one of several evolutionarily conserved genes involved in repair of interstrand cross-links (Dronkert et al., 2000).[supplied by OMIM][3]
# Function
The protein DCLRE1A (DNA cross-link repair 1A) is also referred to as SNM1A (sensitive to nitrogen mustard 1A). DCLRE1A is a 5’ to 3’ exonuclease that forms a complex with the Cockayne syndrome B (CSB) protein. In this complex, CSB modulates the exonuclease activity of DCLRE1A and coordinates the efficient assembly of DCLRE1A to sites of DNA damage.[4] In human cells, this complex is recruited to DNA inter-strand cross-links, a form of DNA damage. The complex then participates in the repair of the cross-linked DNA. DCLRE1A protein is thought to be recruited by CSB to facilitate cross-link unhooking following incision 5’ to the cross-link by another complex, the ERCC1/XPF nuclease complex.[4] Failure of the DCLRE1A/CSB complex to carry out its repair function may contribute to the degenerative pathologies and premature aging features of Cockayne syndrome. | https://www.wikidoc.org/index.php/DCLRE1A | |
deed508b41a637eb8f0a182bd14b44ad639c83f9 | wikidoc | DCLRE1B | DCLRE1B
DNA cross-link repair 1B protein is a protein that in humans is encoded by the DCLRE1B gene.
DNA interstrand cross-links prevent strand separation, thereby physically blocking transcription, replication, and segregation of DNA. DCLRE1B is one of several evolutionarily conserved genes involved in repair of interstrand cross-links (Dronkert et al., 2000).
# Function
The DCLRE1B/SNM1B/Apollo protein is a repair exonuclease that digests double-stranded and single-stranded DNA with a 5’ to 3’ directionality.
Using an SNM1B/Apollo knockout mouse model, evidence was obtained that SNM1B/Apollo protein is required to protect telomeres against illegitimate non-homologous end joining that can result in genomic instabilityy and consequently in multi-organ developmental failure.
In a human patient with Hoyeraal-Hreidarsson syndrome, a dominant negative mutation in the SNM1B/Apollo gene was discovered. This mutation hampered the proper replication of telomeres, leading to major telomeric dysfunction and cellular senescence. SNM1B/Apollo protein appears to be a crucial factor in telomere maintenance, independent of its function in repairing DNA inter-strand crosslinks. | DCLRE1B
DNA cross-link repair 1B protein is a protein that in humans is encoded by the DCLRE1B gene.[1]
DNA interstrand cross-links prevent strand separation, thereby physically blocking transcription, replication, and segregation of DNA. DCLRE1B is one of several evolutionarily conserved genes involved in repair of interstrand cross-links (Dronkert et al., 2000).[supplied by OMIM][1]
# Function
The DCLRE1B/SNM1B/Apollo protein is a repair exonuclease that digests double-stranded and single-stranded DNA with a 5’ to 3’ directionality.[2]
Using an SNM1B/Apollo knockout mouse model, evidence was obtained that SNM1B/Apollo protein is required to protect telomeres against illegitimate non-homologous end joining that can result in genomic instabilityy and consequently in multi-organ developmental failure.[3]
In a human patient with Hoyeraal-Hreidarsson syndrome, a dominant negative mutation in the SNM1B/Apollo gene was discovered.[4] This mutation hampered the proper replication of telomeres, leading to major telomeric dysfunction and cellular senescence. SNM1B/Apollo protein appears to be a crucial factor in telomere maintenance, independent of its function in repairing DNA inter-strand crosslinks.[4] | https://www.wikidoc.org/index.php/DCLRE1B | |
1674ac3f57dcc94b5ebb8331966521e8086792d4 | wikidoc | DEFB126 | DEFB126
Beta-defensin 126 is a protein that in humans is encoded by the DEFB126 gene.
# Function
Defensins are cysteine-rich cationic polypeptides that are important in the immunologic response to invading microorganisms. The protein encoded by this gene is secreted and is a member of the beta defensin protein family. Beta defensin genes are found in several clusters throughout the genome, with this gene mapping to a cluster at 20p13. The encoded protein is highly similar to an epididymal-specific secretory protein (ESP13.2) from cynomolgus monkey.
It has been suggested that a common variation in the DEFB126 gene generates abnormal mRNA and can somewhat impair fertility. | DEFB126
Beta-defensin 126 is a protein that in humans is encoded by the DEFB126 gene.[1][2]
# Function
Defensins are cysteine-rich cationic polypeptides that are important in the immunologic response to invading microorganisms. The protein encoded by this gene is secreted and is a member of the beta defensin protein family. Beta defensin genes are found in several clusters throughout the genome, with this gene mapping to a cluster at 20p13. The encoded protein is highly similar to an epididymal-specific secretory protein (ESP13.2) from cynomolgus monkey.[2]
It has been suggested that a common variation in the DEFB126 gene generates abnormal mRNA and can somewhat impair fertility.[3] | https://www.wikidoc.org/index.php/DEFB126 | |
722d105bb79d394fd313c3ee4dccf216f6c13a0f | wikidoc | DEPDC1B | DEPDC1B
DEP Domain Containing Protein 1B also known as XTP1, XTP8,HBV XAg-Transactivated Protein 8, is a human protein encoded by a gene of similar name located on chromosome 5.
The precise function of DEPDC1B is currently unknown. Expression profiles indicate that DEPDC1B is highly expressed ubiquitously throughout human tissue.
# Gene structure
## Gene neighborhood
DEPDC1B is found on the long arm of chromosome 5 (5q12.1), spanning 103kb on the minus strand. The gene neighborhood of DEPDC1B includes 5 other genes. Downstream are two genes SEPT21 and PDE4D. Upstream are another two genes ELOV7 and KRT8P31. On the complement strand is another gene in the same region PART1.
## Promoter
DEPDC1B promoter region contains several transcription factors associated with proteins of ubiquitous expression. These transcription factors possess a central theme of cellular proliferation, cell cycle regulation, apoptosis, and differentiation. Few promoters unique to tumor suppression or tumorgenesis exist within the region as well.
The following includes the top twenty Predicted Transcription Factors:
# mRNA structure
## Splice variants
DEPDC1B possesses 13 mRNA splice variants that form two isoforms. Isoform 1 is the longest and is the most commonly used version of the gene. It is composed of 11 exons and is 103254bp in length. Isoform 2 is the second confirmed transcript variant. It is composed of 10 exons, missing the tenth exon of the first variant. The missing exon is 186bp in length. See Protein Structure section for more detail...
## Secondary structure
DEPDC1B is predicted to be predominantly alpha-helical. No significant beta-strands or beta structures exist with the protein.
## Stem loops and binding miRNA
DEPDC1B is predicted to possess multiple stem loops in its 5' and 3' untranslated regions (UTR)
. In the 3' UTR, miRNA has-miR-499-5p binds to a nucleotide region predicted as a stem loop.
# Protein structure
## Sequence
The DEPDC1B gene possesses two novel proteoforms. The longest variation, coded by mRNA isoform 1, is the most commonly used. The protein is 529 amino acids in length. The second novel proteoform, DEPDC1B.2 is coded by 10 exons, missing the 10th exon from the longest variation. The protein is 467 amino acids in length. The missing 62 amino acids follow the RhoGAP domain, in a region predicted to be highly phosphorylated
## Domains
DEPDC1B contains two structural domains: a DEP domain and a RhoGAP domain.
The DEP domain is primarily found in proteins involved in G-protein signalling pathways and regulation of GTPase. As well, experimental evidence suggests that the DEP domain determines the subcellular target of some GTPase Activating proteins. In the DEPDC1B protein electronic inference has verified the GTPase activator activity function. The solution structure of human containing DEP domain containing proteins verifies the secondary structure of the domain: containing three alpha-helices and two beta-strands within the approximate 80 amino acid region of the domain.
The RhoGAP domain is another structural domain known to interact with GTPase and small GTPase. Research concerning the domain in other proteins indicates an approximately similar function among the domain in various proteins. The domain has been verified to interact with other proteins to form complexes or interact with other strcuutres of the cell such as the cytoskeleton or plasma membrane.
## Post-translational modification
DEPDC1B protein product is predicted to be highly phosphorylated after translation. A single sumolaytion site, found within the RhoGAP domain, indicates the possible interaction of the protein with a SUMO protein, enabling or inhibiting interaction with other proteins. A single palmitoylation site, found within the RhoGAP domain, indicates the possible interaction of the DEPDC1B protein product with a membrane via lipid anchor.
No conserved glycolation sites are predicted within the mature DEPDC1B protein product. No signal peptide or transmembrane domains are predicted within human or any ortholog protein. No prenylation sites are predicted in any DEPDC1B orthologs.
## Expression
Expression of DEPDC1B is reported to be largely ubiquitous throughout mouse tissue. High level of gene expression is observed in all periods of life, except early zygote stages. Experimental evidence suggests that DEPDC1B presents similar ubiquitous expression in all tissues.
Differential expression profiles suggest that DEPDC1B is higher expressed in many cancerous disease states, including: papillary thyroid cancer, breast cancer, synovial sarcoma, and prostatic cancer progression. Also, DEPDC1B expression decreases in environments of beta-catenin depletion in multiple myeloma cell lines
## Interactions
No interactions of DEPDC1B within any other protein product characterized by experimentation have been verified.
Medium coexpression of DEPDC1B with ECT2 in cell cycle regulation and DNA synthesis was verified by similarity of expression in various tissues. The remaining predicted interaction were determined via datamining.
# Homology
## Orthologs
DEPDC1B is unique to Chordates in Kingdom Animalia
Multiple sequence alignments verify that DEPDC1B is highly conserved among orthologs.
The two structural domains (DEP and RhoGAP) are the two most conserved elements of the proteins. Various motifs are also conserved throughout the protein. No data suggesting motif function could be determined. All predicted post-translational modification were confirmed to be conserved in the orthologous proteins.
DEPDC1B evolution is predicted to follow the general species evolution.
## Paralogs
DEPDC1B possesses two significant paralogs - DEPDC1A and DEPDC7
Multiple sequence alignment and phylogenetic analysis indicates DEPDC1A as the most recent paralog, diverging approximately 600 million years ago. DEPDC1A has been researched in several disease states. High expression of the protein in Multiple Myeloma (MM) malignant plasma cells is associated with patient fatality. The high expression has been confirmed using conditional lentiviral vector delivery “to inhibit growth of human melanoma cell lines (HMCLs), with a block in G2 phase of the cell cycle, p53 phosphorylation and stabilization, and p21Cip1 accumulation”9. In the same study it was concluded that DEPDC1A may contribute to the plasmablast features of MM cells, blocking differentiation. Study of DEPDC1A in bladder carcinogenesis revealed the gene as a possible antigen for the formation of bladder cancer cells. Using microarray and northern blotting confirmed the presence of unsubstantial amounts of the protein within the normal tissues, excluding the testis. Currently the gene is a potential target molecule for therapeutic treatment of bladder carcinogenesis.
No data detailing signigicant function in DEPD7 has been published or recorded. | DEPDC1B
DEP Domain Containing Protein 1B also known as XTP1, XTP8,HBV XAg-Transactivated Protein 8, [formerly referred to as BRCC3] is a human protein encoded by a gene of similar name located on chromosome 5.[1][2][3]
The precise function of DEPDC1B is currently unknown. Expression profiles indicate that DEPDC1B is highly expressed ubiquitously throughout human tissue.[4]
# Gene structure
## Gene neighborhood
DEPDC1B is found on the long arm of chromosome 5 (5q12.1), spanning 103kb on the minus strand. The gene neighborhood of DEPDC1B includes 5 other genes. Downstream are two genes SEPT21 and PDE4D. Upstream are another two genes ELOV7 and KRT8P31. On the complement strand is another gene in the same region PART1.[2]
## Promoter
DEPDC1B promoter region contains several transcription factors associated with proteins of ubiquitous expression. These transcription factors possess a central theme of cellular proliferation, cell cycle regulation, apoptosis, and differentiation. Few promoters unique to tumor suppression or tumorgenesis exist within the region as well.[5]
The following includes the top twenty Predicted Transcription Factors:
# mRNA structure
## Splice variants
DEPDC1B possesses 13 mRNA splice variants that form two isoforms. Isoform 1 is the longest and is the most commonly used version of the gene. It is composed of 11 exons and is 103254bp in length. Isoform 2 is the second confirmed transcript variant. It is composed of 10 exons, missing the tenth exon of the first variant. The missing exon is 186bp in length.[6] See Protein Structure section for more detail...
## Secondary structure
DEPDC1B is predicted to be predominantly alpha-helical. No significant beta-strands or beta structures exist with the protein.
.[7]
## Stem loops and binding miRNA
DEPDC1B is predicted to possess multiple stem loops in its 5' and 3' untranslated regions (UTR)[8][9]
. In the 3' UTR, miRNA has-miR-499-5p binds to a nucleotide region predicted as a stem loop.[10]
# Protein structure
## Sequence
The DEPDC1B gene possesses two novel proteoforms. The longest variation, coded by mRNA isoform 1, is the most commonly used. The protein is 529 amino acids in length. The second novel proteoform, DEPDC1B.2 is coded by 10 exons, missing the 10th exon from the longest variation. The protein is 467 amino acids in length. The missing 62 amino acids follow the RhoGAP domain, in a region predicted to be highly phosphorylated[11]
## Domains
DEPDC1B contains two structural domains: a DEP domain and a RhoGAP domain.
The DEP domain is primarily found in proteins involved in G-protein signalling pathways and regulation of GTPase.[12][13] As well, experimental evidence suggests that the DEP domain determines the subcellular target of some GTPase Activating proteins.[14] In the DEPDC1B protein electronic inference has verified the GTPase activator activity function.[11] The solution structure of human containing DEP domain containing proteins verifies the secondary structure of the domain: containing three alpha-helices and two beta-strands within the approximate 80 amino acid region of the domain.[15][16]
The RhoGAP domain is another structural domain known to interact with GTPase and small GTPase. Research concerning the domain in other proteins indicates an approximately similar function among the domain in various proteins. The domain has been verified to interact with other proteins to form complexes or interact with other strcuutres of the cell such as the cytoskeleton or plasma membrane.[17]
## Post-translational modification
DEPDC1B protein product is predicted to be highly phosphorylated after translation.[18] A single sumolaytion site, found within the RhoGAP domain, indicates the possible interaction of the protein with a SUMO protein, enabling or inhibiting interaction with other proteins.[19] A single palmitoylation site, found within the RhoGAP domain, indicates the possible interaction of the DEPDC1B protein product with a membrane via lipid anchor.[20]
No conserved glycolation sites are predicted within the mature DEPDC1B protein product.[21] No signal peptide or transmembrane domains are predicted within human or any ortholog protein.[22][23] No prenylation sites are predicted in any DEPDC1B orthologs.[24]
## Expression
Expression of DEPDC1B is reported to be largely ubiquitous throughout mouse tissue. High level of gene expression is observed in all periods of life, except early zygote stages.[4] Experimental evidence suggests that DEPDC1B presents similar ubiquitous expression in all tissues.[25]
Differential expression profiles suggest that DEPDC1B is higher expressed in many cancerous disease states, including: papillary thyroid cancer,[26] breast cancer,[27] synovial sarcoma,[28] and prostatic cancer progression.[29] Also, DEPDC1B expression decreases in environments of beta-catenin depletion in multiple myeloma cell lines[30]
## Interactions
No interactions of DEPDC1B within any other protein product characterized by experimentation have been verified.[31]
Medium coexpression of DEPDC1B with ECT2 in cell cycle regulation and DNA synthesis was verified by similarity of expression in various tissues.[31] The remaining predicted interaction were determined via datamining.
# Homology
## Orthologs
DEPDC1B is unique to Chordates in Kingdom Animalia[32]
Multiple sequence alignments verify that DEPDC1B is highly conserved among orthologs.[33][34][35][36]
The two structural domains (DEP and RhoGAP) are the two most conserved elements of the proteins. Various motifs are also conserved throughout the protein. No data suggesting motif function could be determined. All predicted post-translational modification were confirmed to be conserved in the orthologous proteins.
DEPDC1B evolution is predicted to follow the general species evolution.
## Paralogs
DEPDC1B possesses two significant paralogs - DEPDC1A and DEPDC7
Multiple sequence alignment and phylogenetic analysis indicates DEPDC1A as the most recent paralog, diverging approximately 600 million years ago. DEPDC1A has been researched in several disease states. High expression of the protein in Multiple Myeloma (MM) malignant plasma cells is associated with patient fatality. The high expression has been confirmed using conditional lentiviral vector delivery “to inhibit growth of human melanoma cell lines (HMCLs), with a block in G2 phase of the cell cycle, p53 phosphorylation and stabilization, and p21Cip1 accumulation”9.[38] In the same study it was concluded that DEPDC1A may contribute to the plasmablast features of MM cells, blocking differentiation. Study of DEPDC1A in bladder carcinogenesis revealed the gene as a possible antigen for the formation of bladder cancer cells. Using microarray and northern blotting confirmed the presence of unsubstantial amounts of the protein within the normal tissues, excluding the testis. Currently the gene is a potential target molecule for therapeutic treatment of bladder carcinogenesis.[39]
No data detailing signigicant function in DEPD7 has been published or recorded. | https://www.wikidoc.org/index.php/DEPDC1B | |
bddb55e82e7cc3f39c2bc09038ac64705d797100 | wikidoc | DNAJC19 | DNAJC19
Mitochondrial import inner membrane translocase subunit TIM14 is an enzyme that in humans is encoded by the DNAJC19 gene on chromosome 3. TIM14 belongs to the DnaJ family, which has been involved in Hsp40/Hsp70 chaperone systems. As a mitochondrial chaperone, TIM14 functions as part of the TIM23 complex import motor to facilitate the import of nuclear-encoded proteins into the mitochondria. TIM14 also complexes with prohibitin complexes to regulate mitochondrial morphogenesis, and has been implicated in dilated cardiomyopathy with ataxia.
# Structure
The DNAJC19 gene is located on the q arm of chromosome 3 at position 26.33 and it spans 6,065 base pairs. The DNAJC19 gene produces a 6.29 kDa protein composed of 59 amino acids. The protein encoded by the DNAJC19 gene possesses an unusual structure compared to the rest of the DNAJ protein family. Notably, the DNAJ domain of TIM14 is located at the C-terminal rather than the N-terminal, and the transmembrane domain confers membrane-bound localization for TIM14 while other DNAJ proteins are cytosolic. TIM14 orthologs in other species, such as the yeast Tim14 and Mdj2p proteins, confirm localization to the mitochondrial inner membrane.
# Function
TIM14 is required for the ATP-dependent import of mitochondrial pre-proteins into the mitochondrial matrix.The J-domain of TIM14 stimulates mtHsp70 ATPase activity to power this transport.
Additionally, TIM14 helps regulate mitochondrial morphology by complexing with prohibitins to perform disphosphoglycerolipid cardiolipin (CL) remodeling. CL is a key phospholipid in mitochondrial membranes that modulates the fusion and fission of mitochondrial membranes, as well as mitophagy and apoptosis.
# Clinical significance
Defects in DNAJC19 have been observed primarily in cases of dilated cardiomyopathy with ataxia (DCMA), though it has also been associated with growth failure, microcytic anemia, and male genital anomalies. DNAJC19 was first implicated in DCMA in a study on the consanguineous Hutterite population, which has since been confirmed in other European populations. In the clinic, DNAJC19 mutations can be detected by screening for elevated levels of 3-methylglutaconic acid, mitochondrial distress, dilated cardiomyopathy, prolongation of the QT interval in the electrocardiogram, and cerebellar ataxia.
# Interactions
TIM14 interacts with:
- TIMM44,
- mtHsp70,
- TIMM16/PAM16, and
- PHB2. | DNAJC19
Mitochondrial import inner membrane translocase subunit TIM14 is an enzyme that in humans is encoded by the DNAJC19 gene on chromosome 3.[1][2] TIM14 belongs to the DnaJ family, which has been involved in Hsp40/Hsp70 chaperone systems.[3][4] As a mitochondrial chaperone, TIM14 functions as part of the TIM23 complex import motor to facilitate the import of nuclear-encoded proteins into the mitochondria.[3] TIM14 also complexes with prohibitin complexes to regulate mitochondrial morphogenesis, and has been implicated in dilated cardiomyopathy with ataxia.[5]
# Structure
The DNAJC19 gene is located on the q arm of chromosome 3 at position 26.33 and it spans 6,065 base pairs.[2] The DNAJC19 gene produces a 6.29 kDa protein composed of 59 amino acids.[6][7] The protein encoded by the DNAJC19 gene possesses an unusual structure compared to the rest of the DNAJ protein family. Notably, the DNAJ domain of TIM14 is located at the C-terminal rather than the N-terminal, and the transmembrane domain confers membrane-bound localization for TIM14 while other DNAJ proteins are cytosolic. TIM14 orthologs in other species, such as the yeast Tim14 and Mdj2p proteins, confirm localization to the mitochondrial inner membrane.[8]
# Function
TIM14 is required for the ATP-dependent import of mitochondrial pre-proteins into the mitochondrial matrix.The J-domain of TIM14 stimulates mtHsp70 ATPase activity to power this transport.[3]
Additionally, TIM14 helps regulate mitochondrial morphology by complexing with prohibitins to perform disphosphoglycerolipid cardiolipin (CL) remodeling. CL is a key phospholipid in mitochondrial membranes that modulates the fusion and fission of mitochondrial membranes, as well as mitophagy and apoptosis.[5]
# Clinical significance
Defects in DNAJC19 have been observed primarily in cases of dilated cardiomyopathy with ataxia (DCMA), though it has also been associated with growth failure, microcytic anemia, and male genital anomalies. DNAJC19 was first implicated in DCMA in a study on the consanguineous Hutterite population, which has since been confirmed in other European populations.[4][9] In the clinic, DNAJC19 mutations can be detected by screening for elevated levels of 3-methylglutaconic acid, mitochondrial distress, dilated cardiomyopathy, prolongation of the QT interval in the electrocardiogram, and cerebellar ataxia.[9][10]
# Interactions
TIM14 interacts with:
- TIMM44,[3]
- mtHsp70,[3]
- TIMM16/PAM16,[11] and
- PHB2.[5] | https://www.wikidoc.org/index.php/DNAJC19 | |
c61654d8b97bf6451a51d6c93a34db72319ca0d2 | wikidoc | DNAJC30 | DNAJC30
DnaJ homolog subfamily C member 30 (DNAJC30), also known as Williams Beuren syndrome chromosome region 18 protein (WBSCR18), is a protein that in humans is encoded by the DNAJC30 gene. This intronless gene encodes a member of the DNAJ molecular chaperone homology domain-containing protein family. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23.
# Structure
The DNAJC30 gene is an intronless gene composed of only one exon, with the chromosome location 7q11.23 in humans. Its open reading frame (ORF) consists of 681 bp in the human cDNA and 660 bp in the mouse cDNA, which encode proteins of 226 and 219 residues, respectively. They are members of the DNAJ molecular chaperone homology domain-containing protein family.
# Function
DNAJC30 is expressed in many tissues, including the brain, heart, kidney, liver, lung, spleen, stomach, and testis, though no transcripts were found in colon, small intestine, and muscle. This protein has been found to localize to the cytosol and mitochondria of cells. Though its exact biological function has yet to be elucidated, the centromeric location of DNAJC30 on the chromosome has led Merla et al. to postulate that it may contribute to functions such as subtle defects in cognition, transient hypercalcemia, and gastrointestinal problems experienced by Williams Beuren syndrome patients.
# Clinical Significance
This gene is one of several contiguous genes located at 7q11.23 deleted in Williams Beuren syndrome, the others including: elastin, FKBP6, FZD9 (FZD3), BAZ1B (WSTF, WBSCR9), BCL7B, TBL2 (WS-βTRP), WBSCR14 (WS-bHLH), STX1A, CLDN3 (CPETR2, RVP1), CLDN4 (CPETR1), LIMK1, EIF4H (WBSCR1), WBSCR15 (WBSCR5), RFC2, CYLN2 (CLIP-115, WBSCR4, WBSCR3), GTF2IRD1 (WBSCR11, GTF3), and GTF2I (BAP135, SPIN). Williams Beuren syndrome is a neurodevelopmental disorder characterized by congenital heart and vascular disease, hypertension, infantile hypercalcemia, dental abnormalities, dysmorphic facial features, mental retardation, premature aging of the skin, and unique cognitive and personality profiles. While haploinsufficiency of elastin is known to cause the cardiovascular deficiencies, the roles of the other 16 genes in the deleted region, including DNAJC30, have yet to be confirmed. | DNAJC30
DnaJ homolog subfamily C member 30 (DNAJC30), also known as Williams Beuren syndrome chromosome region 18 protein (WBSCR18), is a protein that in humans is encoded by the DNAJC30 gene. This intronless gene encodes a member of the DNAJ molecular chaperone homology domain-containing protein family. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23.[1]
# Structure
The DNAJC30 gene is an intronless gene composed of only one exon, with the chromosome location 7q11.23 in humans.[1] Its open reading frame (ORF) consists of 681 bp in the human cDNA and 660 bp in the mouse cDNA, which encode proteins of 226 and 219 residues, respectively. They are members of the DNAJ molecular chaperone homology domain-containing protein family.[2]
# Function
DNAJC30 is expressed in many tissues, including the brain, heart, kidney, liver, lung, spleen, stomach, and testis, though no transcripts were found in colon, small intestine, and muscle.[2] This protein has been found to localize to the cytosol and mitochondria of cells. [3] Though its exact biological function has yet to be elucidated, the centromeric location of DNAJC30 on the chromosome has led Merla et al. to postulate that it may contribute to functions such as subtle defects in cognition, transient hypercalcemia, and gastrointestinal problems experienced by Williams Beuren syndrome patients. [2]
# Clinical Significance
This gene is one of several contiguous genes located at 7q11.23 deleted in Williams Beuren syndrome, the others including: elastin, FKBP6, FZD9 (FZD3), BAZ1B (WSTF, WBSCR9), BCL7B, TBL2 (WS-βTRP), WBSCR14 (WS-bHLH), STX1A, CLDN3 (CPETR2, RVP1), CLDN4 (CPETR1), LIMK1, EIF4H (WBSCR1), WBSCR15 (WBSCR5), RFC2, CYLN2 (CLIP-115, WBSCR4, WBSCR3), GTF2IRD1 (WBSCR11, GTF3), and GTF2I (BAP135, SPIN). Williams Beuren syndrome is a neurodevelopmental disorder characterized by congenital heart and vascular disease, hypertension, infantile hypercalcemia, dental abnormalities, dysmorphic facial features, mental retardation, premature aging of the skin, and unique cognitive and personality profiles. While haploinsufficiency of elastin is known to cause the cardiovascular deficiencies, the roles of the other 16 genes in the deleted region, including DNAJC30, have yet to be confirmed.[2] | https://www.wikidoc.org/index.php/DNAJC30 | |
b96b455b3f2a8ca5ec15b10860c8f33eb0a1b772 | wikidoc | Damiana | Damiana
Damiana (Turnera diffusa, syn. Turnera aphrodisiaca) is a shrub native to Central and South America. It belongs to the family Turneraceae.
Blooming with small yellow flowers, the shrub has an odor somewhat like chamomile or cannabis sativa, which is due to an oil present in the plant. The leaves have traditionally been made into a tea which was used by native people of Central and South America for its reputed aphrodisiac effects.
Damiana is also a European name. In the country of Bulgaria it is simply a female version of Damian. In Greece the name Damiana refers to a person who is tame and subdued. Additionally, the name Damiana is somewhat common in Latino/Spanish locations.
# Uses
## Herbal Medicine
In herbal medicine, damiana is used to treat conditions ranging from coughs, to constipation, to depression. The herbal supplement is reputed to help with Energy, Emphysema, low Estrogen, Frigidity, Hot Flashes, Impotency, Infertility, Menopause, Parkinson's Disease, PMS, Inflammation of Prostate, Lou Gehrig's disease, and more dealing with reproductive organs in both males and females
## Recreational
Also, a traditional Mexican liqueur, sometimes used in margaritas is made from this herb. Its makers claim that Damiana liqueur was used in the first margarita. | Damiana
Template:Cleanup
Damiana (Turnera diffusa, syn. Turnera aphrodisiaca) is a shrub native to Central and South America. It belongs to the family Turneraceae.
Blooming with small yellow flowers, the shrub has an odor somewhat like chamomile or cannabis sativa, which is due to an oil present in the plant. The leaves have traditionally been made into a tea which was used by native people of Central and South America for its reputed aphrodisiac effects.
Damiana is also a European name. In the country of Bulgaria it is simply a female version of Damian. In Greece the name Damiana refers to a person who is tame and subdued. Additionally, the name Damiana is somewhat common in Latino/Spanish locations.
# Uses
## Herbal Medicine
In herbal medicine, damiana is used to treat conditions ranging from coughs, to constipation, to depression. The herbal supplement is reputed to help with Energy, Emphysema, low Estrogen, Frigidity, Hot Flashes, Impotency, Infertility, Menopause, Parkinson's Disease, PMS, Inflammation of Prostate, Lou Gehrig's disease, and more dealing with reproductive organs in both males and females[1]
## Recreational
Also, a traditional Mexican liqueur, sometimes used in margaritas is made from this herb. Its makers claim that Damiana liqueur was used in the first margarita.[2] | https://www.wikidoc.org/index.php/Damiana | |
03cdd1f36b68d9942041abc6d45303874e26ba08 | wikidoc | Danazol | Danazol
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Black Box Warning
# Overview
Danazol is a estrogen antagonist, endocrine metabolic agent that is FDA approved for the treatment of endometriosis, fibrocystic breast disease, hereditary angioedema. There is a Black Box Warning for this drug as shown here. Common adverse reactions include acne, weight gain.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Danazol capsules are indicated for the treatment of endometriosis amenable to hormonal management.
- Dosing Information
- In moderate to severe disease, or in patients infertile due to endometriosis, a starting dose of 800 mg given in two divided doses is recommended. Amenorrhea and rapid response to painful symptoms is best achieved at this dosage level. Gradual downward titration to a dose sufficient to maintain amenorrhea may be considered depending upon patient response. For mild cases, an initial daily dose of 200 mg to 400 mg given in two divided doses is recommended and may be adjusted depending on patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with danazol. It is essential that therapy continue uninterrupted for 3 to 6 months but may be extended to 9 months if necessary. After termination of therapy, if symptoms recur, treatment can be reinstituted.
- Most cases of symptomatic fibrocystic breast disease may be treated by simple measures (e.g., padded brassieres and analgesics).
- In infrequent patients, symptoms of pain and tenderness may be severe enough to warrant treatment by suppression of ovarian function. Danazol capsules are usually effective in decreasing nodularity, pain, and tenderness. It should be stressed to the patient that this treatment is not innocuous in that it involves considerable alterations of hormone levels and that recurrence of symptoms is very common after cessation of therapy.
- Dosing Information
- The total daily dosage of danazol for fibrocystic breast disease ranges from 100 mg to 400 mg given in two divided doses depending upon patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with danazol. A nonhormonal method of contraception is recommended when danazol is administered at this dose, since ovulation may not be suppressed.
- In most instances, breast pain and tenderness are significantly relieved by the first month and eliminated in 2 to 3 months. Usually elimination of nodularity requires 4 to 6 months of uninterrupted therapy. Regular menstrual patterns, irregular menstrual patterns, and amenorrhea each occur in approximately one-third of patients treated with 100 mg of danazol. Irregular menstrual patterns and amenorrhea are observed more frequently with higher doses. Clinical studies have demonstrated that 50% of patients may show evidence of recurrence of symptoms within one year. In this event, treatment may be reinstated.
- Danazol capsules are indicated for the prevention of attacks of angioedema of all types (cutaneous, abdominal, laryngeal) in males and females.
- Dosing Information
- The dosage requirements for continuous treatment of hereditary angioedema with danazol should be individualized on the basis of the clinical response of the patient. It is recommended that the patient be started on 200 mg, two or three times a day. After a favorable initial response is obtained in terms of prevention of episodes of edematous attacks, the proper continuing dosage should be determined by decreasing the dosage by 50% or less at intervals of one to three months or longer if frequency of attacks prior to treatment dictates. If an attack occurs, the daily dosage may be increased by up to 200 mg. During the dose adjusting phase, close monitoring of the patient's response is indicated, particularly if the patient has a history of airway involvement.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
- There is limited information regarding Off-Label Guideline-Supported Use of Danazol in adult patients.
### Non–Guideline-Supported Use
- There is limited information regarding Off-Label Non–Guideline-Supported Use of Danazol in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- There is limited information regarding FDA-Labeled Use of Danazol in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
- There is limited information regarding Off-Label Guideline-Supported Use of Danazol in pediatric patients.
### Non–Guideline-Supported Use
- There is limited information regarding Off-Label Non–Guideline-Supported Use of Danazol in pediatric patients.
# Contraindications
Danazol capsules should not be administered to patients with:
- Undiagnosed abnormal genital bleeding.
- Markedly impaired hepatic, renal, or cardiac function.
- Pregnancy (see WARNINGS).
- Breast feeding.
- Porphyria - danazol can induce ALA synthetase activity and hence porphyrin metabolism.
- Androgen-dependent tumor.
- Active thrombosis or thromboembolic disease and history of such events.
- Hypersensitivity to danazol.
# Warnings
- A temporary alteration of lipoproteins in the form of decreased high density lipoproteins and possibly increased low density lipoproteins has been reported during danazol therapy. These alterations may be marked, and prescribers should consider the potential impact on the risk of atherosclerosis and coronary artery disease in accordance with the potential benefit of the therapy to the patient.
- Before initiating therapy of fibrocystic breast disease with danazol, carcinoma of the breast should be excluded. However, nodularity, pain, tenderness due to fibrocystic breast disease may prevent recognition of underlying carcinoma before treatment is begun. Therefore, if any nodule persists or enlarges during treatment, carcinoma should be considered and ruled out.
- Patients should be watched closely for signs of androgenic effects some of which may not be reversible even when drug administration is stopped.
### Precautions
- Because danazol may cause some degree of fluid retention, conditions that might be influenced by this factor, such as epilepsy, migraine, or cardiac or renal dysfunction, require careful observation.
- Since hepatic dysfunction manifested by modest increases in serum transaminase levels has been reported in patients treated with danazol, periodic liver function tests should be performed.
- Administration of danazol has been reported to cause exacerbation of the manifestations of acute intermittent porphyria.
Laboratory Tests
- Danazol treatment may interfere with laboratory determinations of testosterone, androstenedione and dehydroepiandrosterone. Other metabolic events include a reduction in thyroid binding globulin and T4 with increased uptake of T3, but without disturbance of thyroid stimulating hormone or of free thyroxin index.
# Adverse Reactions
## Clinical Trials Experience
- The following events have been reported in association with the use of danazol:
- Androgen like effects include weight gain, acne and seborrhea. Mild hirsutism, edema, hair loss, voice change, which may take the form of hoarseness, sore throat or of instability or deepening of pitch, may occur and may persist after cessation of therapy. Hypertrophy of the clitoris is rare.
- Other possible endocrine effects include menstrual disturbances in the form of spotting, alteration of the timing of the cycle and amenorrhea. Although cyclical bleeding and ovulation usually return within 60-90 days after discontinuation of therapy with danazol, persistent amenorrhea has occasionally been reported.
- Flushing, sweating, vaginal dryness and irritation and reduction in breast size, may reflect lowering of estrogen. Nervousness and emotional lability have been reported. In the male a modest reduction in spermatogenesis may be evident during treatment. Abnormalities in semen volume, viscosity, sperm count, and motility may occur in patients receiving long-term therapy.
- Hepatic dysfunction, as evidenced by reversible elevated serum enzymes and/or jaundice, has been reported in patients receiving a daily dosage of danazol of 400 mg or more. It is recommended that patients receiving danazol be monitored for hepatic dysfunction by laboratory tests and clinical observation. Serious hepatic toxicity including cholestatic jaundice, peliosis hepatis, and hepatic adenoma have been reported.
- Abnormalities in laboratory tests may occur during therapy with danazol including CPK, glucose tolerance, glucagon, thyroid binding globulin, sex hormone binding globulin, other plasma proteins, lipids and lipoproteins.
- The following reactions have been reported, a causal relationship to the administration of danazol has neither been confirmed nor refuted: allergic: urticaria, pruritus and rarely, nasal congestion; CNS effects: headache, nervousness and emotional lability, dizziness and fainting, depression, fatigue, sleep disorders, tremor, paresthesias, weakness, visual disturbances, and rarely, benign intracranial hypertension, anxiety, changes in appetite, chills, and rarely convulsions, Guillain-Barre syndrome; gastrointestinal: gastroenteritis, nausea, vomiting, constipation, and rarely, pancreatitis; musculoskeletal: muscle cramps or spasms, or pains, joint pain, joint lockup, joint swelling, pain in back, neck, or extremities, and rarely, carpal tunnel syndrome which may be secondary to fluid retention; genitourinary: hematuria, prolonged posttherapy amenorrhea; hematologic: an increase in red cell and platelet count. Reversible erythrocytosis, leukocytosis or polycythemia may be provoked. Eosinophilia, leukopenia and thrombocytopenia have also been noted. Skin: rashes (maculopapular, vesicular, papular, purpuric, petechial), and rarely, sun sensitivity, Stevens-Johnson syndrome; other: increased insulin requirements in diabetic patients, change in libido, elevation in blood pressure, and rarely, cataracts, bleeding gums, fever, pelvic pain, nipple discharge. Malignant liver tumors have been reported in rare instances, after long-term use.
## Postmarketing Experience
- There is limited information regarding Postmarketing Experience of Danazol in the drug label.
# Drug Interactions
Carcinogenesis, Mutagenesis, Impairment of Fertility
- Current data are insufficient to assess the carcinogenicity of danazol.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): X
Teratogenic Effects
- (see CONTRAINDICATIONS.)
Pregnancy Category X
- Danazol administered orally to pregnant rats from the 6th through the 15th day of gestation at doses up to 250 mg/kg/day (7-15 times the human dose) did not result in drug-induced embryotoxicity or teratogenicity, nor difference in litter size, viability or weight of offspring compared to controls. In rabbits, the administration of danazol on days 6-18 of gestation at doses of 60 mg/kg/day and above (2-4 times the human dose) resulted in inhibition of fetal development.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Danazol in women who are pregnant.
### Labor and Delivery
- There is no FDA guidance on use of Danazol during labor and delivery.
### Nursing Mothers
- (see CONTRAINDICATIONS).
### Pediatric Use
- Safety and effectiveness in pediatric patients have not been established.
### Geriatic Use
- There is no FDA guidance on the use of Danazol with respect to geriatric patients.
### Gender
- There is no FDA guidance on the use of Danazol with respect to specific gender populations.
### Race
- There is no FDA guidance on the use of Danazol with respect to specific racial populations.
### Renal Impairment
- There is no FDA guidance on the use of Danazol in patients with renal impairment.
### Hepatic Impairment
- There is no FDA guidance on the use of Danazol in patients with hepatic impairment.
### Females of Reproductive Potential and Males
- There is no FDA guidance on the use of Danazol in women of reproductive potentials and males.
### Immunocompromised Patients
- There is no FDA guidance one the use of Danazol in patients who are immunocompromised.
# Administration and Monitoring
### Administration
Endometriosis
- In moderate to severe disease, or in patients infertile due to endometriosis, a starting dose of 800 mg given in two divided doses is recommended. Amenorrhea and rapid response to painful symptoms is best achieved at this dosage level. Gradual downward titration to a dose sufficient to maintain amenorrhea may be considered depending upon patient response. For mild cases, an initial daily dose of 200 mg to 400 mg given in two divided doses is recommended and may be adjusted depending on patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with danazol. It is essential that therapy continue uninterrupted for 3 to 6 months but may be extended to 9 months if necessary. After termination of therapy, if symptoms recur, treatment can be reinstituted.
Fibrocystic Breast Disease
- The total daily dosage of danazol for fibrocystic breast disease ranges from 100 mg to 400 mg given in two divided doses depending upon patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with danazol. A nonhormonal method of contraception is recommended when danazol is administered at this dose, since ovulation may not be suppressed.
- In most instances, breast pain and tenderness are significantly relieved by the first month and eliminated in 2 to 3 months. Usually elimination of nodularity requires 4 to 6 months of uninterrupted therapy. Regular menstrual patterns, irregular menstrual patterns, and amenorrhea each occur in approximately one-third of patients treated with 100 mg of danazol. Irregular menstrual patterns and amenorrhea are observed more frequently with higher doses. Clinical studies have demonstrated that 50% of patients may show evidence of recurrence of symptoms within one year. In this event, treatment may be reinstated.
Hereditary Angioedema
- The dosage requirements for continuous treatment of hereditary angioedema with danazol should be individualized on the basis of the clinical response of the patient. It is recommended that the patient be started on 200 mg, two or three times a day. After a favorable initial response is obtained in terms of prevention of episodes of edematous attacks, the proper continuing dosage should be determined by decreasing the dosage by 50% or less at intervals of one to three months or longer if frequency of attacks prior to treatment dictates. If an attack occurs, the daily dosage may be increased by up to 200 mg. During the dose adjusting phase, close monitoring of the patient's response is indicated, particularly if the patient has a history of airway involvement.
### Monitoring
- Danazol may raise the plasma levels of cyclosporin and tacrolimus, leading to an increase of the renal toxicity of these drugs. Monitoring of systemic concentrations of these drugs and appropriate dose adjustments may be needed when used concomitantly with danazol.
- Hepatic dysfunction, as evidenced by reversible elevated serum enzymes and/or jaundice, has been reported in patients receiving a daily dosage of danazol of 400 mg or more. It is recommended that patients receiving danazol be monitored for hepatic dysfunction by laboratory tests and clinical observation. Serious hepatic toxicity including cholestatic jaundice, peliosis hepatis, and hepatic adenoma have been reported.
- The dosage requirements for continuous treatment of hereditary angioedema with danazol should be individualized on the basis of the clinical response of the patient. It is recommended that the patient be started on 200 mg, two or three times a day. During the dose adjusting phase, close monitoring of the patient's response is indicated, particularly if the patient has a history of airway involvement.
# IV Compatibility
- There is limited information regarding IV Compatibility of Danazol in the drug label.
# Overdosage
- There is limited information regarding Chronic Overdose of Danazol in the drug label.
# Pharmacology
## Mechanism of Action
- Danazol suppresses the pituitary-ovarian axis. This suppression is probably a combination of depressed hypothalamic-pituitary response to lowered estrogen production, the alteration of sex steroid metabolism, and interaction of danazol with sex hormone receptors. The only other demonstrable hormonal effect is weak androgenic activity. Danazol depresses the output of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
- Recent evidence suggests a direct inhibitory effect at gonadal sites and a binding of danazol to receptors of gonadal steroids at target organs. In addition, danazol has been shown to significantly decrease IgG, IgM and IgA levels, as well as phospholipid and IgG isotope autoantibodies in patients with endometriosis and associated elevations of autoantibodies, suggesting this could be another mechanism by which it facilitates regression of the disease.
- In the treatment of endometriosis, danazol alters the normal and ectopic endometrial tissue so that it becomes inactive and atrophic. Complete resolution of endometrial lesions occurs in the majority of cases.
- Changes in vaginal cytology and cervical mucus reflect the suppressive effect of danazol on the pituitary-ovarian axis.
- In the treatment of fibrocystic breast disease, danazol usually produces partial to complete disappearance of nodularity and complete relief of pain and tenderness. Changes in the menstrual pattern may occur.
- Generally, the pituitary-suppressive action of danazol is reversible. Ovulation and cyclic bleeding usually return within 60 to 90 days when therapy with danazol is discontinued.
- In the treatment of hereditary angioedema, danazol at effective doses prevents attacks of the disease characterized by episodic edema of the abdominal viscera, extremities, face, and airway which may be disabling and, if the airway is involved, fatal. In addition, danazol corrects partially or completely the primary biochemical abnormality of hereditary angioedema by increasing the levels of the deficient C1 esterase inhibitor (C1El). As a result of this action the serum levels of the C4 component of the complement system are also increased.
## Structure
- Danazol is a synthetic steroid derived from ethisterone. It is a white to pale yellow crystalline powder, practically insoluble or insoluble in water, and sparingly soluble in alcohol. Chemically, danazol is 17α-Pregna-2, 4-dien-20-yno -isoxazol-17-ol. It has the following structural formula:
- Danazol capsules for oral administration contain 50 mg, 100 mg, or 200 mg danazol.
- Inactive Ingredients: anhydrous lactose, lactose monohydrate, magnesium stearate, pregelatinized starch, sodium lauryl sulfate, talc. Capsule shells for 200 mg danazol contain D&C Yellow #10, FD&C Red #40, D&C Red #28, gelatin, and titanium dioxide. Capsule shells for 50 mg and 100 mg danazol contain D&C Yellow # 10, FD&C Red # 40, gelatin, and titanium dioxide. The capsule imprinting ink contains: shellac glaze in ethanol, iron oxide black, n-butyl alcohol, propylene glycol, ethanol, methanol, FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, and D&C Yellow No. 10 Aluminum Lake.
## Pharmacodynamics
- There is limited information regarding Pharmacodynamics of Danazol in the drug label.
## Pharmacokinetics
- Absorption: After oral administration of a 400 mg dose to healthy male volunteers, peak plasma concentrations of danazol are reached between 2 and 8 hours, with a median Tmax value of 4 hours. Steady state conditions are observed following 6 days of twice daily dosing of danazol.
- The pharmacokinetic parameters for danazol after administering a 400 mg oral dose to healthy males are summarized in the following table:
- The pharmacokinetic parameters for danazol after oral administration of 100, 200 and 400 mg single doses to healthy female volunteers are summarized in the following table:
- Dose proportionality: Bioavailability studies indicate that blood levels do not increase proportionally with increases in the administered dose.
- Single dose administration of danazol in healthy female volunteers found that a 4-fold increase in dose produced only a 1.6 and 2.5-fold increase in AUC and a 1.3 and 2.2-fold increase in Cmax in the fasted and fed state, respectively. A similar degree of non-dose proportionality was observed at steady state.
- Food Effect: Single dose administration of 100 mg and 200 mg capsules of danazol to female volunteers showed that both the extent of availability and the maximum plasma concentration increased by 3 to 4 fold, respectively, following a meal (> 30 grams of fat), when compared to the fasted state. Further, food also delayed mean time to peak concentration of danazol by about 30 minutes. Even after multiple dosing under less extreme food/fasting conditions, there remained approximately a 2 to 2.5 fold difference in bioavailability between the fed and fasted states.
- Distribution: Danazol is lipophilic and can partition into cell membranes, indicating the likelihood of distribution into deep tissue compartments.
- Metabolism and Excretion: Danazol appears to be metabolized and the metabolites are eliminated by renal and fecal pathways. The two primary metabolites excreted in the urine are 2-hydroxymethyl danazol and ethisterone. At least ten different products were identified in feces.
- The reported elimination half-life of danazol is variable across studies. The mean half-life of danazol in healthy males is 9.7 h. After 6 months of 200 mg three times a day dosing in endometriosis patients, the half-life of danazol was reported as 23.7 hours.
## Nonclinical Toxicology
- There is limited information regarding Nonclinical Toxicology of Danazol in the drug label.
# Clinical Studies
- There is limited information regarding Clinical Studies of Danazol in the drug label.
# How Supplied
- Danazol Capsules USP, 200 mg are available as orange opaque/orange opaque capsules imprinted with logo "LANNETT" on the cap and "1369" on the body and are supplied in:
- Unit dose packages of 30 (3x10) NDC 68084-074-21.
## Storage
- Store at 20° to 25°C (68° to 77°F).
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
- There is limited information regarding Patient Counseling Information of Danazol in the drug label.
# Precautions with Alcohol
- Alcohol-Danazol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Danocrine
# Look-Alike Drug Names
- A® — B®
# Drug Shortage Status
# Price | Danazol
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Deepika Beereddy, MBBS [2]
# Disclaimer
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# Black Box Warning
# Overview
Danazol is a estrogen antagonist, endocrine metabolic agent that is FDA approved for the treatment of endometriosis, fibrocystic breast disease, hereditary angioedema. There is a Black Box Warning for this drug as shown here. Common adverse reactions include acne, weight gain.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Danazol capsules are indicated for the treatment of endometriosis amenable to hormonal management.
- Dosing Information
- In moderate to severe disease, or in patients infertile due to endometriosis, a starting dose of 800 mg given in two divided doses is recommended. Amenorrhea and rapid response to painful symptoms is best achieved at this dosage level. Gradual downward titration to a dose sufficient to maintain amenorrhea may be considered depending upon patient response. For mild cases, an initial daily dose of 200 mg to 400 mg given in two divided doses is recommended and may be adjusted depending on patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with danazol. It is essential that therapy continue uninterrupted for 3 to 6 months but may be extended to 9 months if necessary. After termination of therapy, if symptoms recur, treatment can be reinstituted.
- Most cases of symptomatic fibrocystic breast disease may be treated by simple measures (e.g., padded brassieres and analgesics).
- In infrequent patients, symptoms of pain and tenderness may be severe enough to warrant treatment by suppression of ovarian function. Danazol capsules are usually effective in decreasing nodularity, pain, and tenderness. It should be stressed to the patient that this treatment is not innocuous in that it involves considerable alterations of hormone levels and that recurrence of symptoms is very common after cessation of therapy.
- Dosing Information
- The total daily dosage of danazol for fibrocystic breast disease ranges from 100 mg to 400 mg given in two divided doses depending upon patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with danazol. A nonhormonal method of contraception is recommended when danazol is administered at this dose, since ovulation may not be suppressed.
- In most instances, breast pain and tenderness are significantly relieved by the first month and eliminated in 2 to 3 months. Usually elimination of nodularity requires 4 to 6 months of uninterrupted therapy. Regular menstrual patterns, irregular menstrual patterns, and amenorrhea each occur in approximately one-third of patients treated with 100 mg of danazol. Irregular menstrual patterns and amenorrhea are observed more frequently with higher doses. Clinical studies have demonstrated that 50% of patients may show evidence of recurrence of symptoms within one year. In this event, treatment may be reinstated.
- Danazol capsules are indicated for the prevention of attacks of angioedema of all types (cutaneous, abdominal, laryngeal) in males and females.
- Dosing Information
- The dosage requirements for continuous treatment of hereditary angioedema with danazol should be individualized on the basis of the clinical response of the patient. It is recommended that the patient be started on 200 mg, two or three times a day. After a favorable initial response is obtained in terms of prevention of episodes of edematous attacks, the proper continuing dosage should be determined by decreasing the dosage by 50% or less at intervals of one to three months or longer if frequency of attacks prior to treatment dictates. If an attack occurs, the daily dosage may be increased by up to 200 mg. During the dose adjusting phase, close monitoring of the patient's response is indicated, particularly if the patient has a history of airway involvement.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
- There is limited information regarding Off-Label Guideline-Supported Use of Danazol in adult patients.
### Non–Guideline-Supported Use
- There is limited information regarding Off-Label Non–Guideline-Supported Use of Danazol in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- There is limited information regarding FDA-Labeled Use of Danazol in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
- There is limited information regarding Off-Label Guideline-Supported Use of Danazol in pediatric patients.
### Non–Guideline-Supported Use
- There is limited information regarding Off-Label Non–Guideline-Supported Use of Danazol in pediatric patients.
# Contraindications
Danazol capsules should not be administered to patients with:
- Undiagnosed abnormal genital bleeding.
- Markedly impaired hepatic, renal, or cardiac function.
- Pregnancy (see WARNINGS).
- Breast feeding.
- Porphyria - danazol can induce ALA synthetase activity and hence porphyrin metabolism.
- Androgen-dependent tumor.
- Active thrombosis or thromboembolic disease and history of such events.
- Hypersensitivity to danazol.
# Warnings
- A temporary alteration of lipoproteins in the form of decreased high density lipoproteins and possibly increased low density lipoproteins has been reported during danazol therapy. These alterations may be marked, and prescribers should consider the potential impact on the risk of atherosclerosis and coronary artery disease in accordance with the potential benefit of the therapy to the patient.
- Before initiating therapy of fibrocystic breast disease with danazol, carcinoma of the breast should be excluded. However, nodularity, pain, tenderness due to fibrocystic breast disease may prevent recognition of underlying carcinoma before treatment is begun. Therefore, if any nodule persists or enlarges during treatment, carcinoma should be considered and ruled out.
- Patients should be watched closely for signs of androgenic effects some of which may not be reversible even when drug administration is stopped.
### Precautions
- Because danazol may cause some degree of fluid retention, conditions that might be influenced by this factor, such as epilepsy, migraine, or cardiac or renal dysfunction, require careful observation.
- Since hepatic dysfunction manifested by modest increases in serum transaminase levels has been reported in patients treated with danazol, periodic liver function tests should be performed.
- Administration of danazol has been reported to cause exacerbation of the manifestations of acute intermittent porphyria.
Laboratory Tests
- Danazol treatment may interfere with laboratory determinations of testosterone, androstenedione and dehydroepiandrosterone. Other metabolic events include a reduction in thyroid binding globulin and T4 with increased uptake of T3, but without disturbance of thyroid stimulating hormone or of free thyroxin index.
# Adverse Reactions
## Clinical Trials Experience
- The following events have been reported in association with the use of danazol:
- Androgen like effects include weight gain, acne and seborrhea. Mild hirsutism, edema, hair loss, voice change, which may take the form of hoarseness, sore throat or of instability or deepening of pitch, may occur and may persist after cessation of therapy. Hypertrophy of the clitoris is rare.
- Other possible endocrine effects include menstrual disturbances in the form of spotting, alteration of the timing of the cycle and amenorrhea. Although cyclical bleeding and ovulation usually return within 60-90 days after discontinuation of therapy with danazol, persistent amenorrhea has occasionally been reported.
- Flushing, sweating, vaginal dryness and irritation and reduction in breast size, may reflect lowering of estrogen. Nervousness and emotional lability have been reported. In the male a modest reduction in spermatogenesis may be evident during treatment. Abnormalities in semen volume, viscosity, sperm count, and motility may occur in patients receiving long-term therapy.
- Hepatic dysfunction, as evidenced by reversible elevated serum enzymes and/or jaundice, has been reported in patients receiving a daily dosage of danazol of 400 mg or more. It is recommended that patients receiving danazol be monitored for hepatic dysfunction by laboratory tests and clinical observation. Serious hepatic toxicity including cholestatic jaundice, peliosis hepatis, and hepatic adenoma have been reported.
- Abnormalities in laboratory tests may occur during therapy with danazol including CPK, glucose tolerance, glucagon, thyroid binding globulin, sex hormone binding globulin, other plasma proteins, lipids and lipoproteins.
- The following reactions have been reported, a causal relationship to the administration of danazol has neither been confirmed nor refuted: allergic: urticaria, pruritus and rarely, nasal congestion; CNS effects: headache, nervousness and emotional lability, dizziness and fainting, depression, fatigue, sleep disorders, tremor, paresthesias, weakness, visual disturbances, and rarely, benign intracranial hypertension, anxiety, changes in appetite, chills, and rarely convulsions, Guillain-Barre syndrome; gastrointestinal: gastroenteritis, nausea, vomiting, constipation, and rarely, pancreatitis; musculoskeletal: muscle cramps or spasms, or pains, joint pain, joint lockup, joint swelling, pain in back, neck, or extremities, and rarely, carpal tunnel syndrome which may be secondary to fluid retention; genitourinary: hematuria, prolonged posttherapy amenorrhea; hematologic: an increase in red cell and platelet count. Reversible erythrocytosis, leukocytosis or polycythemia may be provoked. Eosinophilia, leukopenia and thrombocytopenia have also been noted. Skin: rashes (maculopapular, vesicular, papular, purpuric, petechial), and rarely, sun sensitivity, Stevens-Johnson syndrome; other: increased insulin requirements in diabetic patients, change in libido, elevation in blood pressure, and rarely, cataracts, bleeding gums, fever, pelvic pain, nipple discharge. Malignant liver tumors have been reported in rare instances, after long-term use.
## Postmarketing Experience
- There is limited information regarding Postmarketing Experience of Danazol in the drug label.
# Drug Interactions
Carcinogenesis, Mutagenesis, Impairment of Fertility
- Current data are insufficient to assess the carcinogenicity of danazol.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): X
Teratogenic Effects
- (see CONTRAINDICATIONS.)
Pregnancy Category X
- Danazol administered orally to pregnant rats from the 6th through the 15th day of gestation at doses up to 250 mg/kg/day (7-15 times the human dose) did not result in drug-induced embryotoxicity or teratogenicity, nor difference in litter size, viability or weight of offspring compared to controls. In rabbits, the administration of danazol on days 6-18 of gestation at doses of 60 mg/kg/day and above (2-4 times the human dose) resulted in inhibition of fetal development.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Danazol in women who are pregnant.
### Labor and Delivery
- There is no FDA guidance on use of Danazol during labor and delivery.
### Nursing Mothers
- (see CONTRAINDICATIONS).
### Pediatric Use
- Safety and effectiveness in pediatric patients have not been established.
### Geriatic Use
- There is no FDA guidance on the use of Danazol with respect to geriatric patients.
### Gender
- There is no FDA guidance on the use of Danazol with respect to specific gender populations.
### Race
- There is no FDA guidance on the use of Danazol with respect to specific racial populations.
### Renal Impairment
- There is no FDA guidance on the use of Danazol in patients with renal impairment.
### Hepatic Impairment
- There is no FDA guidance on the use of Danazol in patients with hepatic impairment.
### Females of Reproductive Potential and Males
- There is no FDA guidance on the use of Danazol in women of reproductive potentials and males.
### Immunocompromised Patients
- There is no FDA guidance one the use of Danazol in patients who are immunocompromised.
# Administration and Monitoring
### Administration
Endometriosis
- In moderate to severe disease, or in patients infertile due to endometriosis, a starting dose of 800 mg given in two divided doses is recommended. Amenorrhea and rapid response to painful symptoms is best achieved at this dosage level. Gradual downward titration to a dose sufficient to maintain amenorrhea may be considered depending upon patient response. For mild cases, an initial daily dose of 200 mg to 400 mg given in two divided doses is recommended and may be adjusted depending on patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with danazol. It is essential that therapy continue uninterrupted for 3 to 6 months but may be extended to 9 months if necessary. After termination of therapy, if symptoms recur, treatment can be reinstituted.
Fibrocystic Breast Disease
- The total daily dosage of danazol for fibrocystic breast disease ranges from 100 mg to 400 mg given in two divided doses depending upon patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with danazol. A nonhormonal method of contraception is recommended when danazol is administered at this dose, since ovulation may not be suppressed.
- In most instances, breast pain and tenderness are significantly relieved by the first month and eliminated in 2 to 3 months. Usually elimination of nodularity requires 4 to 6 months of uninterrupted therapy. Regular menstrual patterns, irregular menstrual patterns, and amenorrhea each occur in approximately one-third of patients treated with 100 mg of danazol. Irregular menstrual patterns and amenorrhea are observed more frequently with higher doses. Clinical studies have demonstrated that 50% of patients may show evidence of recurrence of symptoms within one year. In this event, treatment may be reinstated.
Hereditary Angioedema
- The dosage requirements for continuous treatment of hereditary angioedema with danazol should be individualized on the basis of the clinical response of the patient. It is recommended that the patient be started on 200 mg, two or three times a day. After a favorable initial response is obtained in terms of prevention of episodes of edematous attacks, the proper continuing dosage should be determined by decreasing the dosage by 50% or less at intervals of one to three months or longer if frequency of attacks prior to treatment dictates. If an attack occurs, the daily dosage may be increased by up to 200 mg. During the dose adjusting phase, close monitoring of the patient's response is indicated, particularly if the patient has a history of airway involvement.
### Monitoring
- Danazol may raise the plasma levels of cyclosporin and tacrolimus, leading to an increase of the renal toxicity of these drugs. Monitoring of systemic concentrations of these drugs and appropriate dose adjustments may be needed when used concomitantly with danazol.
- Hepatic dysfunction, as evidenced by reversible elevated serum enzymes and/or jaundice, has been reported in patients receiving a daily dosage of danazol of 400 mg or more. It is recommended that patients receiving danazol be monitored for hepatic dysfunction by laboratory tests and clinical observation. Serious hepatic toxicity including cholestatic jaundice, peliosis hepatis, and hepatic adenoma have been reported.
- The dosage requirements for continuous treatment of hereditary angioedema with danazol should be individualized on the basis of the clinical response of the patient. It is recommended that the patient be started on 200 mg, two or three times a day. During the dose adjusting phase, close monitoring of the patient's response is indicated, particularly if the patient has a history of airway involvement.
# IV Compatibility
- There is limited information regarding IV Compatibility of Danazol in the drug label.
# Overdosage
- There is limited information regarding Chronic Overdose of Danazol in the drug label.
# Pharmacology
## Mechanism of Action
- Danazol suppresses the pituitary-ovarian axis. This suppression is probably a combination of depressed hypothalamic-pituitary response to lowered estrogen production, the alteration of sex steroid metabolism, and interaction of danazol with sex hormone receptors. The only other demonstrable hormonal effect is weak androgenic activity. Danazol depresses the output of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
- Recent evidence suggests a direct inhibitory effect at gonadal sites and a binding of danazol to receptors of gonadal steroids at target organs. In addition, danazol has been shown to significantly decrease IgG, IgM and IgA levels, as well as phospholipid and IgG isotope autoantibodies in patients with endometriosis and associated elevations of autoantibodies, suggesting this could be another mechanism by which it facilitates regression of the disease.
- In the treatment of endometriosis, danazol alters the normal and ectopic endometrial tissue so that it becomes inactive and atrophic. Complete resolution of endometrial lesions occurs in the majority of cases.
- Changes in vaginal cytology and cervical mucus reflect the suppressive effect of danazol on the pituitary-ovarian axis.
- In the treatment of fibrocystic breast disease, danazol usually produces partial to complete disappearance of nodularity and complete relief of pain and tenderness. Changes in the menstrual pattern may occur.
- Generally, the pituitary-suppressive action of danazol is reversible. Ovulation and cyclic bleeding usually return within 60 to 90 days when therapy with danazol is discontinued.
- In the treatment of hereditary angioedema, danazol at effective doses prevents attacks of the disease characterized by episodic edema of the abdominal viscera, extremities, face, and airway which may be disabling and, if the airway is involved, fatal. In addition, danazol corrects partially or completely the primary biochemical abnormality of hereditary angioedema by increasing the levels of the deficient C1 esterase inhibitor (C1El). As a result of this action the serum levels of the C4 component of the complement system are also increased.
## Structure
- Danazol is a synthetic steroid derived from ethisterone. It is a white to pale yellow crystalline powder, practically insoluble or insoluble in water, and sparingly soluble in alcohol. Chemically, danazol is 17α-Pregna-2, 4-dien-20-yno [2, 3-d]-isoxazol-17-ol. It has the following structural formula:
- Danazol capsules for oral administration contain 50 mg, 100 mg, or 200 mg danazol.
- Inactive Ingredients: anhydrous lactose, lactose monohydrate, magnesium stearate, pregelatinized starch, sodium lauryl sulfate, talc. Capsule shells for 200 mg danazol contain D&C Yellow #10, FD&C Red #40, D&C Red #28, gelatin, and titanium dioxide. Capsule shells for 50 mg and 100 mg danazol contain D&C Yellow # 10, FD&C Red # 40, gelatin, and titanium dioxide. The capsule imprinting ink contains: shellac glaze in ethanol, iron oxide black, n-butyl alcohol, propylene glycol, ethanol, methanol, FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, and D&C Yellow No. 10 Aluminum Lake.
## Pharmacodynamics
- There is limited information regarding Pharmacodynamics of Danazol in the drug label.
## Pharmacokinetics
- Absorption: After oral administration of a 400 mg dose to healthy male volunteers, peak plasma concentrations of danazol are reached between 2 and 8 hours, with a median Tmax value of 4 hours. Steady state conditions are observed following 6 days of twice daily dosing of danazol.
- The pharmacokinetic parameters for danazol after administering a 400 mg oral dose to healthy males are summarized in the following table:
- The pharmacokinetic parameters for danazol after oral administration of 100, 200 and 400 mg single doses to healthy female volunteers are summarized in the following table:
- Dose proportionality: Bioavailability studies indicate that blood levels do not increase proportionally with increases in the administered dose.
- Single dose administration of danazol in healthy female volunteers found that a 4-fold increase in dose produced only a 1.6 and 2.5-fold increase in AUC and a 1.3 and 2.2-fold increase in Cmax in the fasted and fed state, respectively. A similar degree of non-dose proportionality was observed at steady state.
- Food Effect: Single dose administration of 100 mg and 200 mg capsules of danazol to female volunteers showed that both the extent of availability and the maximum plasma concentration increased by 3 to 4 fold, respectively, following a meal (> 30 grams of fat), when compared to the fasted state. Further, food also delayed mean time to peak concentration of danazol by about 30 minutes. Even after multiple dosing under less extreme food/fasting conditions, there remained approximately a 2 to 2.5 fold difference in bioavailability between the fed and fasted states.
- Distribution: Danazol is lipophilic and can partition into cell membranes, indicating the likelihood of distribution into deep tissue compartments.
- Metabolism and Excretion: Danazol appears to be metabolized and the metabolites are eliminated by renal and fecal pathways. The two primary metabolites excreted in the urine are 2-hydroxymethyl danazol and ethisterone. At least ten different products were identified in feces.
- The reported elimination half-life of danazol is variable across studies. The mean half-life of danazol in healthy males is 9.7 h. After 6 months of 200 mg three times a day dosing in endometriosis patients, the half-life of danazol was reported as 23.7 hours.
## Nonclinical Toxicology
- There is limited information regarding Nonclinical Toxicology of Danazol in the drug label.
# Clinical Studies
- There is limited information regarding Clinical Studies of Danazol in the drug label.
# How Supplied
- Danazol Capsules USP, 200 mg are available as orange opaque/orange opaque capsules imprinted with logo "LANNETT" on the cap and "1369" on the body and are supplied in:
- Unit dose packages of 30 (3x10) NDC 68084-074-21.
## Storage
- Store at 20° to 25°C (68° to 77°F)[see USP Controlled Room Temperature].
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
- There is limited information regarding Patient Counseling Information of Danazol in the drug label.
# Precautions with Alcohol
- Alcohol-Danazol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Danocrine
# Look-Alike Drug Names
- A® — B®[1]
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Danazol | |
2c2ed9f4531788e0c4e6c4365c53e085128a4f9d | wikidoc | Dantron | Dantron
# Overview
Dantron (INN), also known as chrysazin or 1,8-dihydroxyanthraquinone, is an organic substance, formally derived from anthraquinone by the replacement of two hydrogen atoms by hydroxyl groups (–OH). It is used in some countries as a stimulant laxative.
It should not be confused with ondansetron, an unrelated drug that was marketed in South Africa under the trade name "Dantron".
# Medical uses
In the USA, dantron is not used because it is considered to be a carcinogen.
In the UK it is considered a possible carcinogen and so its licence is restricted to patients who already have a diagnosis of terminal cancer. It is mainly used in palliative care to counteract the constipating effects of opioids. Its British Approved Name was danthron, but it has now been changed to "dantron", the recommended International Nonproprietary Name.
Dantron has the notable side-effect of causing red-colored urine. | Dantron
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Dantron (INN), also known as chrysazin or 1,8-dihydroxyanthraquinone, is an organic substance, formally derived from anthraquinone by the replacement of two hydrogen atoms by hydroxyl groups (–OH). It is used in some countries as a stimulant laxative.
It should not be confused with ondansetron, an unrelated drug that was marketed in South Africa under the trade name "Dantron".
# Medical uses
In the USA, dantron is not used because it is considered to be a carcinogen.[1]
In the UK it is considered a possible carcinogen and so its licence is restricted to patients who already have a diagnosis of terminal cancer. It is mainly used in palliative care to counteract the constipating effects of opioids. Its British Approved Name was danthron, but it has now been changed to "dantron", the recommended International Nonproprietary Name.[2]
Dantron has the notable side-effect of causing red-colored urine. | https://www.wikidoc.org/index.php/Dantron | |
668c3330677cd0ae7c72738c6380d56c9a13b61f | wikidoc | Estriol | Estriol
# Overview
Estriol (also oestriol) is one of the three main estrogens produced by the human body. It is only produced in significant amounts during pregnancy as it is made by the placenta. In pregnant women with multiple sclerosis (MS), estriol reduces the disease's symptoms noticeably, according to researchers at UCLA's Geffen Medical School.
Levels of estriol in non-pregnant women do not change much after menopause, and levels are not significantly different from levels in men.
# Use in screening
Estriol levels can be measured to give an indication of the general health of the fetus. DHEA-S is produced by the adrenal cortex of the fetus. This is converted to estriol by the placenta.
If levels of "unconjugated estriol" are abnormally low in a pregnant woman, this may indicate a problem with the development of the child. It is included as part of the triple test. | Estriol
Template:Chembox new
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Estriol (also oestriol) is one of the three main estrogens produced by the human body. It is only produced in significant amounts during pregnancy as it is made by the placenta. In pregnant women with multiple sclerosis (MS), estriol reduces the disease's symptoms noticeably, according to researchers at UCLA's Geffen Medical School.
Levels of estriol in non-pregnant women do not change much after menopause, and levels are not significantly different from levels in men.
# Use in screening
Estriol levels can be measured to give an indication of the general health of the fetus. DHEA-S is produced by the adrenal cortex of the fetus. This is converted to estriol by the placenta.
If levels of "unconjugated estriol" are abnormally low in a pregnant woman, this may indicate a problem with the development of the child.[1] It is included as part of the triple test. | https://www.wikidoc.org/index.php/Ddx:Estriol | |
2382bbde61fffb60f1716eb7638fd0c16f635ebf | wikidoc | Gastrin | Gastrin
Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas.
Gastrin binds to cholecystokinin B receptors to stimulate the release of histamines in enterochromaffin-like cells, and it induces the insertion of K+/H+ ATPase pumps into the apical membrane of parietal cells (which in turn increases H+ release into the stomach cavity). Its release is stimulated by peptides in the lumen of the stomach.
# Physiology
## Genetics
In humans, the GAS gene is located on the long arm of the seventeenth chromosome (17q21).
## Synthesis
Gastrin is a linear peptide hormone produced by G cells of the duodenum and in the pyloric antrum of the stomach. It is secreted into the bloodstream. The encoded polypeptide is preprogastrin, which is cleaved by enzymes in posttranslational modification to produce progastrin (an intermediate, inactive precursor) and then gastrin in various forms, primarily the following three:
- gastrin-34 ("big gastrin")
- gastrin-17 ("little gastrin")
- gastrin-14 ("minigastrin")
Also, pentagastrin is an artificially synthesized, five amino acid sequence identical to the last five amino acid sequence at the C-terminus end of gastrin.
The numbers refer to the amino acid count.
## Release
Gastrin is released in response to certain stimuli. These include:
- stomach antrum distension
- vagal stimulation (mediated by the neurocrine bombesin, or GRP in humans)
- the presence of partially digested proteins, especially amino acids, in the stomach. Aromatic amino acids are particularly powerful stimuli for gastrin release.
- hypercalcemia (via calcium-sensing receptors)
Gastrin release is inhibited by:
- the presence of acid (primarily the secreted HCl) in the stomach (a case of negative feedback)
- somatostatin also inhibits the release of gastrin, along with secretin, GIP (gastroinhibitory peptide), VIP (vasoactive intestinal peptide), glucagon and calcitonin.
## Function
The presence of gastrin stimulates parietal cells of the stomach to secrete hydrochloric acid (HCl)/gastric acid. This is done both directly on the parietal cell and indirectly via binding onto CCK2/gastrin receptors on ECL cells in the stomach, which then responds by releasing histamine, which in turn acts in a paracrine manner on parietal cells stimulating them to secrete H+ ions. This is the major stimulus for acid secretion by parietal cells.
Along with the above-mentioned function, gastrin has been shown to have additional functions as well:
- Stimulates parietal cell maturation and fundal growth.
- Causes chief cells to secrete pepsinogen, the zymogen (inactive) form of the digestive enzyme pepsin.
- Increases antral muscle mobility and promotes stomach contractions.
- Strengthens antral contractions against the pylorus, and relaxes the pyloric sphincter, which increases the rate of gastric emptying.
- Plays a role in the relaxation of the ileocecal valve.
- Induces pancreatic secretions and gallbladder emptying.
- May impact lower esophageal sphincter (LES) tone, causing it to contract, - although pentagastrin, rather than endogenous gastrin, may be the cause.
- Gastrin contributes to the gastrocolic reflex.
## Factors influencing secretion
### Physiologic
- Stimulatory factors: dietary protein and amino acids (meat), hypercalcemia. (i.e. during the gastric phase)
- Inhibitory factor: acidity (pH below 3) - a negative feedback mechanism, exerted via the release of somatostatin from δ cells in the stomach, which inhibits gastrin and histamine release.
- Stimulatory factor: bombesin or gastrin-releasing peptide (GRP)
- Inhibitory factor: somatostatin - acts on somatostatin-2 receptors on G cells. in a paracrine manner via local diffusion in the intercellular spaces, but also systemically through its release into the local mucosal blood circulation; it inhibits acid secretion by acting on parietal cells.
- Stimulatory factors: Beta-adrenergic agents, cholinergic agents, gastrin-releasing peptide (GRP)
- Inhibitory factor: Enterogastric reflex
- Stimulatory factor: epinephrine
- Inhibitory factors:gastric inhibitory peptide (GIP), secretin, somatostatin, glucagon, calcitonin
### Pathophysiologic
- Gastrinoma paraneoplastic oversecretion (see Role in disease)
# Role in disease
In the Zollinger–Ellison syndrome, gastrin is produced at excessive levels, often by a gastrinoma (gastrin-producing tumor, mostly benign) of the duodenum or the pancreas. To investigate for hypergastrinemia (high blood levels of gastrin), a "pentagastrin test" can be performed.
In autoimmune gastritis, the immune system attacks the parietal cells leading to hypochlorhydria (low stomach acid secretion). This results in an elevated gastrin level in an attempt to compensate for increased pH in the stomach. Eventually, all the parietal cells are lost and achlorhydria results leading to a loss of negative feedback on gastrin secretion. Plasma gastrin concentration is elevated in virtually all individuals with mucolipidosis type IV (mean 1507 pg/mL; range 400-4100 pg/mL) (normal 0-200 pg/mL) secondary to a constitutive achlorhydria. This finding facilitates the diagnosis of patients with this neurogenetic disorder. Additionally, elevated gastrin levels may be present in chronic gastritis resulting from H pylori infection.
# History
Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins, and gastrins were isolated in 1964 by Hilda J. Tracy and Roderic Alfred Gregory at the University of Liverpool. In 1964 the structure of gastrin was determined. | Gastrin
Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas.
Gastrin binds to cholecystokinin B receptors to stimulate the release of histamines in enterochromaffin-like cells, and it induces the insertion of K+/H+ ATPase pumps into the apical membrane of parietal cells (which in turn increases H+ release into the stomach cavity). Its release is stimulated by peptides in the lumen of the stomach.
# Physiology
## Genetics
In humans, the GAS gene is located on the long arm of the seventeenth chromosome (17q21).[1]
## Synthesis
Gastrin is a linear peptide hormone produced by G cells of the duodenum and in the pyloric antrum of the stomach. It is secreted into the bloodstream. The encoded polypeptide is preprogastrin, which is cleaved by enzymes in posttranslational modification to produce progastrin (an intermediate, inactive precursor) and then gastrin in various forms, primarily the following three:
- gastrin-34 ("big gastrin")
- gastrin-17 ("little gastrin")
- gastrin-14 ("minigastrin")
Also, pentagastrin is an artificially synthesized, five amino acid sequence identical to the last five amino acid sequence at the C-terminus end of gastrin.
The numbers refer to the amino acid count.
## Release
Gastrin is released in response to certain stimuli. These include:[citation needed]
- stomach antrum distension
- vagal stimulation (mediated by the neurocrine bombesin, or GRP in humans)
- the presence of partially digested proteins, especially amino acids, in the stomach. Aromatic amino acids are particularly powerful stimuli for gastrin release.[2]
- hypercalcemia (via calcium-sensing receptors[3])
Gastrin release is inhibited by:[4][5]
- the presence of acid (primarily the secreted HCl) in the stomach (a case of negative feedback)
- somatostatin also inhibits the release of gastrin, along with secretin, GIP (gastroinhibitory peptide), VIP (vasoactive intestinal peptide), glucagon and calcitonin.
## Function
The presence of gastrin stimulates parietal cells of the stomach to secrete hydrochloric acid (HCl)/gastric acid. This is done both directly on the parietal cell and indirectly via binding onto CCK2/gastrin receptors on ECL cells in the stomach, which then responds by releasing histamine, which in turn acts in a paracrine manner on parietal cells stimulating them to secrete H+ ions. This is the major stimulus for acid secretion by parietal cells.[citation needed]
Along with the above-mentioned function, gastrin has been shown to have additional functions as well:
- Stimulates parietal cell maturation and fundal growth.
- Causes chief cells to secrete pepsinogen, the zymogen (inactive) form of the digestive enzyme pepsin.
- Increases antral muscle mobility and promotes stomach contractions.
- Strengthens antral contractions against the pylorus, and relaxes the pyloric sphincter, which increases the rate of gastric emptying.[6]
- Plays a role in the relaxation of the ileocecal valve.[7]
- Induces pancreatic secretions and gallbladder emptying.[8]
- May impact lower esophageal sphincter (LES) tone, causing it to contract,[9] - although pentagastrin, rather than endogenous gastrin, may be the cause.[10]
- Gastrin contributes to the gastrocolic reflex.
## Factors influencing secretion
### Physiologic
- Stimulatory factors: dietary protein and amino acids (meat), hypercalcemia. (i.e. during the gastric phase)
- Inhibitory factor: acidity (pH below 3) - a negative feedback mechanism, exerted via the release of somatostatin from δ cells in the stomach, which inhibits gastrin and histamine release.
- Stimulatory factor: bombesin or gastrin-releasing peptide (GRP)
- Inhibitory factor: somatostatin - acts on somatostatin-2 receptors on G cells. in a paracrine manner via local diffusion in the intercellular spaces, but also systemically through its release into the local mucosal blood circulation; it inhibits acid secretion by acting on parietal cells.
- Stimulatory factors: Beta-adrenergic agents, cholinergic agents, gastrin-releasing peptide (GRP)
- Inhibitory factor: Enterogastric reflex
- Stimulatory factor: epinephrine
- Inhibitory factors:gastric inhibitory peptide (GIP), secretin, somatostatin, glucagon, calcitonin
### Pathophysiologic
- Gastrinoma paraneoplastic oversecretion (see Role in disease)
# Role in disease
In the Zollinger–Ellison syndrome, gastrin is produced at excessive levels, often by a gastrinoma (gastrin-producing tumor, mostly benign) of the duodenum or the pancreas. To investigate for hypergastrinemia (high blood levels of gastrin), a "pentagastrin test" can be performed.[citation needed]
In autoimmune gastritis, the immune system attacks the parietal cells leading to hypochlorhydria (low stomach acid secretion). This results in an elevated gastrin level in an attempt to compensate for increased pH in the stomach. Eventually, all the parietal cells are lost and achlorhydria results leading to a loss of negative feedback on gastrin secretion. Plasma gastrin concentration is elevated in virtually all individuals with mucolipidosis type IV (mean 1507 pg/mL; range 400-4100 pg/mL) (normal 0-200 pg/mL) secondary to a constitutive achlorhydria. This finding facilitates the diagnosis of patients with this neurogenetic disorder.[11] Additionally, elevated gastrin levels may be present in chronic gastritis resulting from H pylori infection.[12]
# History
Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins,[13][14] and gastrins were isolated in 1964 by Hilda J. Tracy and Roderic Alfred Gregory at the University of Liverpool.[15] In 1964 the structure of gastrin was determined.[16] | https://www.wikidoc.org/index.php/Ddx:Gastrin | |
4dfd2cbe3b3226a8f6fced4878533596a4c4112c | wikidoc | HLA-B27 | HLA-B27
Human Leukocyte Antigen B*27 (subtypes B*2701-2724) is a class I surface antigen encoded by the B locus in the major histocompatibility complex (MHC) on chromosome 6 and presents microbial antigens to T-cells. HLA-B27 strongly associated with a certain set of autoimmune diseases referred to as the "seronegative spondyloarthropathies". In the general population, about 8% Caucasian, 4% African, 2-9% Chinese, and 0.1-0.5% Japanese have the HLA-B27 antigen. In Northern Scandinavia (Lapland), 24% of people are HLA-B27 positive while 1.8% have ankylosing spondylitis (AS).
# Mystery
The relationship between HLA-B27 and many diseases has not yet been fully elucidated. Though it is associated with a wide range of pathology, it does not appear to be the sole mediator in development of disease. For example, while nearly all people with ankylosing spondylitis (AS) are HLA-B27 positive, only a fraction of people with HLA-B27 ever develop AS. This raises two important questions: why don't all HLA-B27 positive people develop AS, and why do some (although rarely) people who are HLA-B27 negative develop it? The literature is inconclusive, though several theories have been suggested and research continues.
# Associated pathology
In addition to its connection with AS, HLA-B27 is implicated in Reiter's syndrome, certain eye disorders such as acute anterior uveitis and iritis, psoriatic arthritis and Crohn's disease. Reiter's syndrome then again, is statistically associated with AS. | HLA-B27
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Human Leukocyte Antigen B*27 (subtypes B*2701-2724) is a class I surface antigen encoded by the B locus in the major histocompatibility complex (MHC) on chromosome 6 and presents microbial antigens to T-cells. HLA-B27 strongly associated with a certain set of autoimmune diseases referred to as the "seronegative spondyloarthropathies". In the general population, about 8% Caucasian, 4% African, 2-9% Chinese, and 0.1-0.5% Japanese have the HLA-B27 antigen. In Northern Scandinavia (Lapland), 24% of people are HLA-B27 positive while 1.8% have ankylosing spondylitis (AS).
# Mystery
The relationship between HLA-B27 and many diseases has not yet been fully elucidated. Though it is associated with a wide range of pathology, it does not appear to be the sole mediator in development of disease. For example, while nearly all people with ankylosing spondylitis (AS) are HLA-B27 positive, only a fraction of people with HLA-B27 ever develop AS. This raises two important questions: why don't all HLA-B27 positive people develop AS, and why do some (although rarely) people who are HLA-B27 negative develop it? The literature is inconclusive, though several theories have been suggested and research continues.
# Associated pathology
In addition to its connection with AS, HLA-B27 is implicated in Reiter's syndrome, certain eye disorders such as acute anterior uveitis and iritis, psoriatic arthritis and Crohn's disease. Reiter's syndrome then again, is statistically associated with AS. | https://www.wikidoc.org/index.php/Ddx:HLA-B27 | |
3d9886e0b7b80e46c2616c433111aa7ae5c6f548 | wikidoc | Retinol | Retinol
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Retinol is a vitamin analog that is FDA approved for the treatment of acne vulgaris. Common adverse reactions include hypopigmentation, hyperpigmentation, skin erythema.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- RETIN-A is indicated for topical application in the treatment of acne vulgaris. The safety and efficacy of the long-term use of this product in the treatment of other disorders have not been established.
- RETIN-A Gel, Cream or Liquid should be applied once a day, before retiring, to the skin where acne lesions appear, using enough to cover the entire affected area lightly. Liquid: The liquid may be applied using a fingertip, gauze pad, or cotton swab. If gauze or cotton is employed, care should be taken not to oversaturate it to the extent that the liquid would run into areas where treatment is not intended. Gel: Excessive application results in “pilling” of the gel, which minimizes the likelihood of over application by the patient.
- Application may cause a transitory feeling of warmth or slight stinging. In cases where it has been necessary to temporarily discontinue therapy or to reduce the frequency of application, therapy may be resumed or frequency of application increased when the patients become able to tolerate the treatment.
- Alterations of vehicle, drug concentration, or dose frequency should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance.
- During the early weeks of therapy, an apparent exacerbation of inflammatory lesions may occur. This is due to the action of the medication on deep, previously unseen lesions and should not be considered a reason to discontinue therapy.
- Therapeutic results should be noticed after two to three weeks but more than six weeks of therapy may be required before definite beneficial effects are seen.
- Once the acne lesions have responded satisfactorily, it may be possible to maintain the improvement with less frequent applications, or other dosage forms.
- Patients treated with RETIN-A (tretinoin) acne treatment may use cosmetics, but the area to be treated should be cleansed thoroughly before the medication is applied.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Retinol in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Retinol in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Retinol in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Retinol in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Retinol in pediatric patients.
# Contraindications
- Use of the product should be discontinued if hypersensitivity to any of the ingredients is noted.
# Warnings
There is limited information regarding Retinol Warnings' in the drug label.
# Adverse Reactions
## Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Retinol in the drug label.
## Postmarketing Experience
- The skin of certain sensitive individuals may become excessively red, edematous, blistered, or crusted. If these effects occur, the medication should either be discontinued until the integrity of the skin is restored, or the medication should be adjusted to a level the patient can tolerate. True contact allergy to topical tretinoin is rarely encountered.
- Temporary hyper or hypopigmentation has been reported with repeated application of RETIN-A. Some individuals have been reported to have heightened susceptibility to sunlight while under treatment with RETIN-A. To date, all adverse effects of RETIN-A have been reversible upon discontinuance of therapy
# Drug Interactions
There is limited information regarding Retinol Drug Interactions in the drug label.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): C
- Oral tretinoin has been shown to be teratogenic in rats when given in doses 1000 times the topical human dose. Oral tretinoin has been shown to be fetotoxic in rats when given in doses 500 times the topical human dose.
- Topical tretinoin has not been shown to be teratogenic in rats and rabbits when given in doses of 100 and 320 times the topical human dose, respectively (assuming a 50 kg adult applies 250 mg of 0.1% cream topically). However, at these topical doses, delayed ossification of a number of bones occurred in both species. These changes may be considered variants of normal development and are usually corrected after weaning. There are no adequate and well-controlled studies in pregnant women. Tretinoin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Retinol in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Retinol during labor and delivery.
### Nursing Mothers
- It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when RETIN-A is administered to a nursing woman.
### Pediatric Use
There is no FDA guidance on the use of Retinol with respect to pediatric patients.
### Geriatic Use
There is no FDA guidance on the use of Retinol with respect to geriatric patients.
### Gender
There is no FDA guidance on the use of Retinol with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Retinol with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Retinol in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Retinol in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Retinol in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Retinol in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral
- Topical
### Monitoring
- Alterations of vehicle, drug concentration, or dose frequency should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance.
# IV Compatibility
There is limited information regarding IV Compatibility of Retinol in the drug label.
# Overdosage
- If medication is applied excessively, no more rapid or better results will be obtained and marked redness, peeling, or discomfort may occur. Oral ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of Vitamin A
# Pharmacology
## Mechanism of Action
- Although the exact mode of action of tretinoin is unknown, current evidence suggests that topical tretinoin decreases cohesiveness of follicular epithelial cells with decreased microcomedo formation. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells causing extrusion of the comedone.
## Structure
- RETIN-A Gel, Cream and Liquid, containing tretinoin are used for the topical treatment of acne vulgaris. RETIN-A Gel contains tretinoin (retinoic acid, vitamin A acid) in either of two strengths, 0.025% or 0.01% by weight, in a gel vehicle of butylated hydroxytoluene, hydroxypropyl cellulose and alcohol (denatured with tert-butyl alcohol and brucine sulfate) 90% w/w. RETIN-A (tretinoin) Cream contains tretinoin in either of three strengths, 0.1%, 0.05%, or 0.025% by weight, in a hydrophilic cream vehicle of stearic acid, isopropyl myristate, polyoxyl 40 stearate, stearyl alcohol, xanthan gum, sorbic acid, butylated hydroxytoluene, and purified water. RETIN-A Liquid contains tretinoin 0.05% by weight, polyethylene glycol 400, butylated hydroxytoluene and alcohol (denatured with tert-butyl alcohol and brucine sulfate) 55%. Chemically, tretinoin is all-trans-retinoic acid and has the following structure:
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Retinol in the drug label.
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Retinol in the drug label.
## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Retinol in the drug label.
# Clinical Studies
There is limited information regarding Clinical Studies of Retinol in the drug label.
# How Supplied
## Storage
- RETIN-A Liquid, 0.05%, and RETIN-A Gel, 0.025% and 0.01%: store below 86°F. RETIN-A Cream, 0.1%, 0.05%, and 0.025%: store below 80°F.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Retinol in the drug label.
# Precautions with Alcohol
- Alcohol-Retinol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
There is limited information regarding Retinol Brand Names in the drug label.
# Look-Alike Drug Names
There is limited information regarding Retinol Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Retinol
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Retinol is a vitamin analog that is FDA approved for the treatment of acne vulgaris. Common adverse reactions include hypopigmentation, hyperpigmentation, skin erythema.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- RETIN-A is indicated for topical application in the treatment of acne vulgaris. The safety and efficacy of the long-term use of this product in the treatment of other disorders have not been established.
- RETIN-A Gel, Cream or Liquid should be applied once a day, before retiring, to the skin where acne lesions appear, using enough to cover the entire affected area lightly. Liquid: The liquid may be applied using a fingertip, gauze pad, or cotton swab. If gauze or cotton is employed, care should be taken not to oversaturate it to the extent that the liquid would run into areas where treatment is not intended. Gel: Excessive application results in “pilling” of the gel, which minimizes the likelihood of over application by the patient.
- Application may cause a transitory feeling of warmth or slight stinging. In cases where it has been necessary to temporarily discontinue therapy or to reduce the frequency of application, therapy may be resumed or frequency of application increased when the patients become able to tolerate the treatment.
- Alterations of vehicle, drug concentration, or dose frequency should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance.
- During the early weeks of therapy, an apparent exacerbation of inflammatory lesions may occur. This is due to the action of the medication on deep, previously unseen lesions and should not be considered a reason to discontinue therapy.
- Therapeutic results should be noticed after two to three weeks but more than six weeks of therapy may be required before definite beneficial effects are seen.
- Once the acne lesions have responded satisfactorily, it may be possible to maintain the improvement with less frequent applications, or other dosage forms.
- Patients treated with RETIN-A (tretinoin) acne treatment may use cosmetics, but the area to be treated should be cleansed thoroughly before the medication is applied.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Retinol in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Retinol in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Retinol in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Retinol in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Retinol in pediatric patients.
# Contraindications
- Use of the product should be discontinued if hypersensitivity to any of the ingredients is noted.
# Warnings
There is limited information regarding Retinol Warnings' in the drug label.
# Adverse Reactions
## Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Retinol in the drug label.
## Postmarketing Experience
- The skin of certain sensitive individuals may become excessively red, edematous, blistered, or crusted. If these effects occur, the medication should either be discontinued until the integrity of the skin is restored, or the medication should be adjusted to a level the patient can tolerate. True contact allergy to topical tretinoin is rarely encountered.
- Temporary hyper or hypopigmentation has been reported with repeated application of RETIN-A. Some individuals have been reported to have heightened susceptibility to sunlight while under treatment with RETIN-A. To date, all adverse effects of RETIN-A have been reversible upon discontinuance of therapy
# Drug Interactions
There is limited information regarding Retinol Drug Interactions in the drug label.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): C
- Oral tretinoin has been shown to be teratogenic in rats when given in doses 1000 times the topical human dose. Oral tretinoin has been shown to be fetotoxic in rats when given in doses 500 times the topical human dose.
- Topical tretinoin has not been shown to be teratogenic in rats and rabbits when given in doses of 100 and 320 times the topical human dose, respectively (assuming a 50 kg adult applies 250 mg of 0.1% cream topically). However, at these topical doses, delayed ossification of a number of bones occurred in both species. These changes may be considered variants of normal development and are usually corrected after weaning. There are no adequate and well-controlled studies in pregnant women. Tretinoin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Retinol in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Retinol during labor and delivery.
### Nursing Mothers
- It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when RETIN-A is administered to a nursing woman.
### Pediatric Use
There is no FDA guidance on the use of Retinol with respect to pediatric patients.
### Geriatic Use
There is no FDA guidance on the use of Retinol with respect to geriatric patients.
### Gender
There is no FDA guidance on the use of Retinol with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Retinol with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Retinol in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Retinol in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Retinol in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Retinol in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral
- Topical
### Monitoring
- Alterations of vehicle, drug concentration, or dose frequency should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance.
# IV Compatibility
There is limited information regarding IV Compatibility of Retinol in the drug label.
# Overdosage
- If medication is applied excessively, no more rapid or better results will be obtained and marked redness, peeling, or discomfort may occur. Oral ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of Vitamin A
# Pharmacology
## Mechanism of Action
- Although the exact mode of action of tretinoin is unknown, current evidence suggests that topical tretinoin decreases cohesiveness of follicular epithelial cells with decreased microcomedo formation. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells causing extrusion of the comedone.
## Structure
- RETIN-A Gel, Cream and Liquid, containing tretinoin are used for the topical treatment of acne vulgaris. RETIN-A Gel contains tretinoin (retinoic acid, vitamin A acid) in either of two strengths, 0.025% or 0.01% by weight, in a gel vehicle of butylated hydroxytoluene, hydroxypropyl cellulose and alcohol (denatured with tert-butyl alcohol and brucine sulfate) 90% w/w. RETIN-A (tretinoin) Cream contains tretinoin in either of three strengths, 0.1%, 0.05%, or 0.025% by weight, in a hydrophilic cream vehicle of stearic acid, isopropyl myristate, polyoxyl 40 stearate, stearyl alcohol, xanthan gum, sorbic acid, butylated hydroxytoluene, and purified water. RETIN-A Liquid contains tretinoin 0.05% by weight, polyethylene glycol 400, butylated hydroxytoluene and alcohol (denatured with tert-butyl alcohol and brucine sulfate) 55%. Chemically, tretinoin is all-trans-retinoic acid and has the following structure:
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Retinol in the drug label.
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Retinol in the drug label.
## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Retinol in the drug label.
# Clinical Studies
There is limited information regarding Clinical Studies of Retinol in the drug label.
# How Supplied
## Storage
- RETIN-A Liquid, 0.05%, and RETIN-A Gel, 0.025% and 0.01%: store below 86°F. RETIN-A Cream, 0.1%, 0.05%, and 0.025%: store below 80°F.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Retinol in the drug label.
# Precautions with Alcohol
- Alcohol-Retinol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
There is limited information regarding Retinol Brand Names in the drug label.
# Look-Alike Drug Names
There is limited information regarding Retinol Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Ddx:Retinol | |
d2edbef5f5de2b2af5058e4e5ea19e8012ad27a4 | wikidoc | Stridor | Stridor
# Overview
Stridor is a high pitched sound resulting from turbulent gas flow in the upper airway. It may be inspiratory, expiratory or present on both inspiration and expiration. It can be indicative of serious airway obstruction from severe conditions such as epiglottitis, a foreign body lodged in the airway, or a laryngeal tumor. Stridor is indicative of a potential medical emergency and should always command attention. Wherever possible, attempts should be made to immediately establish the cause of the stridor (e.g., foreign body, vocal cord edema, tracheal compression by tumor, functional laryngeal dyskinesia, etc.) That examination requires visualization of the airway by a team of medical experts equipped to control the airway.
# Causes
## Common Causes
### Inspiratory stridor
- Allergy
- Anaphylaxis
- Angioneurotic edema
- Aortic aneurysm
- Aspiration
- Bacterial tracheitis
- Choanal atresia
- Diptheria
- Enlarged tonsils/adnoids
- Epiglottitis
- Facial fracture
- Foreign body aspiration
- Goiter
- Hemangioma
- Inhalation injury
- Laryngeal or tracheal abnormalities
- Laryngomalacia
- Larynx Carcinoma
- Laryngo-tracheal bronchitis
- Laryngeal fracture
- Maxillo-facial dysplasis
- Mandibular fracture
- Medastinal tumor
- Nasal polyp
- Nasal septum deviation
- Neck or facial swelling
- Nerve paresis
- Neck surgery
- Prolonged intubation
- Post-radiation
- Psychogenic
- Retropharyngeal abscess
- Scar stenosis
- Secretions
- Spasmodic croup
- Subglottic stenosis
- Tonsillitis
- Trauma
- Vocal cord cancer
- Vocal cord paralysis
### Expiratory stridor
- Bronchitis
- Bronchial asthma
- Cardiac Failure
- Compression of the bronchii due to lymph node enlargement
- COPD
- Foreign body aspiration
- Pleura process
- Pneumonia
- Pneumothorax
- Trachiobronchitis
- Tumor infiltration
## Causes by Organ System
## Causes in Alphabetical Order
- Aberrant subclavian artery abnormality
- Acenaphthene
- Acetic acid
- Acrylic acid
- Acute diphtheria
- Acute epiglottitis
- Acute laryngitis
- Acute laryngotracheobronchitis
- Acute lymphoblastic leukemia
- Acute pseudo-membranous croup
- Adenoid cystic carcinoma
- Adenovirus
- Airway edema
- Airway obstruction
- Airway trauma
- Alanycarb
- Aldicarb
- Aldoxycarb
- Allergic reaction
- Allyxycarb
- Amidithion
- Aminocarb
- Amiton
- Ammonia
- Anaphylaxis
- Angioedema
- Angioneurotic edema
- Ankylosis of crico-arytenoid joint in rheumatoid arthritis
- Aortic aneurysm
- Arizona bark scorpion poisoning
- Arnold-chiari malformation type 2
- Aromatic amino acid decarboxylase deficiency
- Aspiration
- Asthma-like conditions
- Athyl-gusathion
- Azinfosethyl
- Azinphos
- Azinphosmetile
- Azothoate
- Bacterial tracheitis
- Barium
- Bendiocarb
- Benfuracarb
- Benign tumor of larynx
- Benign tumor of trachea
- Benoxafos
- Bromophos
- Bronchial carcinoma
- Bronchial asthma
- Bronchiolitis obliterans
- Bronchitis
- Bronchogenic carcinoma
- Bronchogenic cyst
- Bronchomalacia
- Bronchopathia osteoplastica
- Bronchopulmonary dysplasia
- Bronchoscopy
- Browntail moth caterpillar poisoning
- Bufencarb
- Bulbar palsy
- Burn injuries
- Butacarb
- Butocarboxim
- Byssinosis
- C1 esterase inhibitor (c1-inh) deficiency
- Cadusafos
- Calcium hypochlorite
- Captafol
- Carbanolate
- Carbaryl
- Carbofuran
- Carbophenothion
- Carbosulfan
- Carcinoid
- Carcinoma of larynx
- Carcinoma of the esophagus
- Carcinoma of the thryoid
- Carcinoma of trachea
- Cardiac failure
- Caustic ingestion
- Cellulitis of neck
- Chlorfenvinphos
- Chlorine dioxide
- Chlorine
- Chloropyrifos
- Choanal atresia
- Chronic lower respiratory diseases
- Chronic obstructive pulmonary disease
- Chronic tuberculous laryngitis
- Classical hodgkin disease
- Cloethocarb
- Common cold
- Compression of bronchii
- Congenital bronchial anomalies
- Congenital laryngeal anomalies
- Congenital laryngeal paralysis in newborns
- Congenital laryngeal stridor
- Congenital subglottic narrowing
- Congenital tracheal anomalies
- Craniofacial anomaly
- Cricoarytenoid ankylosis
- Croup
- Cyanthoate
- Decarbofuran
- Demeton
- Deviated septum
- Dialifos
- Diazinon
- Dichlorvos
- Dicresyl
- Dicrotophos
- Diffuse leiomyomatosis with alport syndrome
- Dimetan
- Dimethoate
- Dimetilan
- Dioxacarb
- Dioxathion
- Diptheria
- Dislocated cricothyroid or cricoarytenoid articulation
- Disulfoton
- Double aortic arch
- Down's syndrome
- Drug allergies
- Edema of the glottis
- Empc
- Endothion
- Enlarged adenoids
- Enlarged tonsils
- Epidermoid carcinoma
- Epiglottitis
- Estrogen dependent hereditary angioedema
- Ethiofencarb
- Ethion
- Ethoate-methyl
- Ethoprophos
- Ethylenediamine
- Ethyl-guthion
- Etrimfos
- Facial fracture
- Fenchlorphos
- Fenethacarb
- Fenitrothion
- Fenobucarb
- Fensulfothion
- Fenthion
- Fonophos
- Food additive allergy
- Food allergies
- Food allergy related asthma
- Foreign body aspiration
- Formaldehyde
- Formothion
- Fresh mangrove caterpillar poisoning
- Furathiocarb
- Gastroesophageal reflux disease
- Gay-feinmesser-cohen syndrome
- Gerhardt syndrome
- Glutaraldehyde
- Goiter
- Granulomatosis with polyangiitis
- Grapeleaf skeletonizer caterpillar poisoning
- Guthion (ethyl)
- Hashimoto's disease
- Hemangioma
- Heptenophos
- Hexamethylene diisocyanate
- Hodgkin's disease
- Hodgkin's lymphoma
- Hydrocephalus
- Hyquincarb
- Idiopathic subglottic tracheal stenosis
- Infectious conditions
- Infectious mononucleosis
- Inhalant abuse
- Inhalation injury
- Inhaled foreign body
- Injury to larynx
- Injury to trachea
- Insect allergy
- Internal laryngeal trauma
- Intrathoracic goitre
- Iodofenphos
- Isoprocarb
- Laryngeal carcinoma
- Laryngeal cleft
- Laryngeal cyst
- Laryngeal fracture
- Laryngeal inflammation
- Laryngeal nerve palsy
- Laryngeal or tracheal abnormalities
- Laryngeal papilloma
- Laryngeal papillomatosis
- Laryngeal stenosis
- Laryngeal web
- Laryngitis
- Laryngocele
- Laryngomalacia
- Laryngoscopy
- Laryngospasm
- Laryngotracheitis
- Laryngotracheobronchitis
- Larynx atresia
- Larynx carcinoma
- Larynx condition
- Latex catheters induced allergies
- Lepidopterism
- Lingual cyst
- Linguinal angioedema
- Local anaesthetic allergy
- Ludwig's angina
- Lung cancer
- Lymphocyte depletion hodgkin's disease
- Macroglossia
- Malathion
- Malignant disease of lower cervical lymph nodes
- Malignant germ cell tumor
- Mandibular fracture
- Mastocytosis
- Maxillo-facial dysplasis
- Mecarbam
- Mediastinal hodgkin's disease
- Mediastinal tumors
- Mesothelioma
- Metabolic disorders
- Metapneumovirus
- Methacrifos
- Methamidophos
- Methidathion
- Methiocarb
- Methomyl
- Metiltriazotion
- Metolcarb
- Mevinphos
- Mexacarbate
- Mixed cellularity hodgkin's disease
- Mixed type non small cell carcinoma
- Monocrotophos
- Morphine allergy
- Nasal polyp
- Nasal septum deviation
- Nasopharyngeal mass
- Neck or facial swelling
- Nerve paresis
- Neural tube defect
- Nickel
- Nitrilacarb
- Nodular goiter
- Nodular sclerosing hodgkin's lymphoma
- Non-small cell lung cancer
- Novacaine drug allergy
- Occupational asthma
- Omethoate
- Osmium
- Oxamyl
- Oxydeprofos
- Oxydisulfoton
- Palladium
- Paragonimiases
- Parathion methyl
- Partial atrioventricular canal
- Peanut allergy
- Penicillin allergy
- Pepper spray
- Peritonsillar abscess
- Phenkapton
- Phorate
- Phosalone
- Phosdrin
- Phosgene oxime
- Phosmet
- Phosphamidon
- Phoxim
- Piriform aperture stenosis
- Pirimicarb
- Pirimiphos-methyl
- Platinum
- Pleura process
- Pneumonia
- Pneumothorax
- Polychondritis
- Post-radiation
- Post-traumatic stenosis of larynx
- Post-traumatic stenosis of the trachea
- Potassium permanganate
- Primary ciliary dyskinesia
- Primiphos methyl
- Profenofos
- Prolonged intubation
- Promacyl
- Promecarb
- Propoxur
- Prothidathion
- Prothoate
- Pseudobulbar palsy
- Psychogenic
- Pulmonary cystic lymphangiectasis
- Pulmonary lymphangiectasia
- Pulmonary pseudolymphoma
- Pyrimitate
- Quinalphos
- Quintiofos
- Recurrent respiratory papillomatosis
- Respiratory tract cancer
- Retropharyngeal abscess
- Retrosternal thyroid
- Rheumatoid disease
- Rhinosinusitis
- Riedel's thyroiditis
- Sarcoidosis
- Satin moth caterpillar poisoning
- Scar stenosis
- Seafood allergy
- Secretions
- Shy-drager syndrome
- Silver
- Small cell lung cancer
- Small jaw
- Smokers throat
- Smoking cessation
- Sophamide
- Spasmodic croup
- Spice allergy
- Sputum
- Squamous cell carcinoma
- Stinging bark caterpillar poisoning
- Stinging nettle caterpillar poisoning
- Stinging rose caterpillar poisoning
- Strictures of main bronchi in sarcoidosis
- Subglottic hemangioma
- Subglottic stenosis
- Sulfa antibiotics allergy
- Sulfotep
- Sulfur trioxide
- Supraglottic webs
- Syphilis
- Syphilitic laryngitis with stenosis
- Tacrine toxicity
- Tazimcarb
- Terbufos
- Tetraethyl pyrophosphate
- Thiocarboxime
- Thiodicarb
- Thiofanox
- Thiometon
- Thoracic aortic aneurysm
- Thymic epithelial tumor
- Thyroglossic cyst
- Thyroidectomy
- Tolclofos methyl
- Tonsillitis
- Tracheal cancer
- Tracheal intubation
- Tracheal stenosis
- Tracheobronchomalacia
- Tracheobronchopathia osteoplastica
- Tracheolaryngobronchitis
- Tracheomalacia
- Tracheopathia osteoplastica
- Tracheostomy
- Trachiobronchitis
- Transfusion reaction
- Trauma
- Triazophos
- Triazotion
- Trifenfos
- Trimellitic anhydride
- Trimethacarb
- Tuberculin
- Tuberculosis
- Tuberculous nodes in mediastinum
- Tuberculous strictures of main bronchi
- Tumor infiltration
- Upper airway burns
- Uranium
- Vamidothion
- Vanadium toxicity
- Vanadium
- Vascular rings
- Vasculitis
- Vocal cord cancer
- Vocal cord paralysis
- Weeping fig poisoning
- Wegener's granulomatosis
- Xmc
- Xylylcarb
# Treatments
The first issue of clinical concern in the setting of stridor is whether or not tracheal intubation or tracheostomy is immediately necessary. Some patients will need immediate tracheal intubation. If intubation can be delayed for a period a number of other potential options can be considered, depending on the severity of the situation and other clinical details. These include:
- Expectant management with full monitoring, oxygen by face mask, and positioning the head of the bed for optimum conditions (e.g., 45 - 90 degrees)
- Use of nebulized racemic epinephrine (0.5 to 0.75 ml of 2.25% racemic epinephrine added to 2.5 to 3 ml of normal saline) in cases where airway edema may be the cause of the stridor. ( Nebulized Cocaine in a dose not exceeding 3 mg/kg may also be used, but not together with racemic epinephrine .)
- Use of dexamethasone (Decadron) 4-8 mg IV q 8 - 12 h in cases where airway edema may be the cause of the stridor; note that some time (in the range of hours) may be need for dexamethasone to work fully.
- Use of inhaled Heliox (70% helium, 30% oxygen); the effect is almost instantaneous
# Diagnosis
Stridor is usually diagnosed the basis of history and physical examination, with a view to revealing the underlying problem or condition.
Chest and neck x-rays, CT-scans, and / or MRIs may reveal structural pathology.
Flexible fiberoptic bronchoscopy can also be very helpful, especially in assessing vocal cord function of in looking for signs of compression or infection. | Stridor
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Luke Rusowicz-Orazem, B.S.
# Overview
Stridor is a high pitched sound resulting from turbulent gas flow in the upper airway. It may be inspiratory, expiratory or present on both inspiration and expiration. It can be indicative of serious airway obstruction from severe conditions such as epiglottitis, a foreign body lodged in the airway, or a laryngeal tumor. Stridor is indicative of a potential medical emergency and should always command attention. Wherever possible, attempts should be made to immediately establish the cause of the stridor (e.g., foreign body, vocal cord edema, tracheal compression by tumor, functional laryngeal dyskinesia, etc.) That examination requires visualization of the airway by a team of medical experts equipped to control the airway.
# Causes
## Common Causes
### Inspiratory stridor
- Allergy
- Anaphylaxis
- Angioneurotic edema
- Aortic aneurysm
- Aspiration
- Bacterial tracheitis
- Choanal atresia
- Diptheria
- Enlarged tonsils/adnoids
- Epiglottitis
- Facial fracture
- Foreign body aspiration
- Goiter
- Hemangioma
- Inhalation injury
- Laryngeal or tracheal abnormalities
- Laryngomalacia
- Larynx Carcinoma
- Laryngo-tracheal bronchitis
- Laryngeal fracture
- Maxillo-facial dysplasis
- Mandibular fracture
- Medastinal tumor
- Nasal polyp
- Nasal septum deviation
- Neck or facial swelling
- Nerve paresis
- Neck surgery
- Prolonged intubation
- Post-radiation
- Psychogenic
- Retropharyngeal abscess
- Scar stenosis
- Secretions
- Spasmodic croup
- Subglottic stenosis
- Tonsillitis
- Trauma
- Vocal cord cancer
- Vocal cord paralysis
### Expiratory stridor
- Bronchitis
- Bronchial asthma
- Cardiac Failure
- Compression of the bronchii due to lymph node enlargement
- COPD
- Foreign body aspiration
- Pleura process
- Pneumonia
- Pneumothorax
- Trachiobronchitis
- Tumor infiltration
## Causes by Organ System
## Causes in Alphabetical Order
- Aberrant subclavian artery abnormality
- Acenaphthene
- Acetic acid
- Acrylic acid
- Acute diphtheria
- Acute epiglottitis
- Acute laryngitis
- Acute laryngotracheobronchitis
- Acute lymphoblastic leukemia
- Acute pseudo-membranous croup
- Adenoid cystic carcinoma
- Adenovirus
- Airway edema
- Airway obstruction
- Airway trauma
- Alanycarb
- Aldicarb
- Aldoxycarb
- Allergic reaction
- Allyxycarb
- Amidithion
- Aminocarb
- Amiton
- Ammonia
- Anaphylaxis
- Angioedema
- Angioneurotic edema
- Ankylosis of crico-arytenoid joint in rheumatoid arthritis
- Aortic aneurysm
- Arizona bark scorpion poisoning
- Arnold-chiari malformation type 2
- Aromatic amino acid decarboxylase deficiency
- Aspiration
- Asthma-like conditions
- Athyl-gusathion
- Azinfosethyl
- Azinphos
- Azinphosmetile
- Azothoate
- Bacterial tracheitis
- Barium
- Bendiocarb
- Benfuracarb
- Benign tumor of larynx
- Benign tumor of trachea
- Benoxafos
- Bromophos
- Bronchial carcinoma
- Bronchial asthma
- Bronchiolitis obliterans
- Bronchitis
- Bronchogenic carcinoma
- Bronchogenic cyst
- Bronchomalacia
- Bronchopathia osteoplastica
- Bronchopulmonary dysplasia
- Bronchoscopy
- Browntail moth caterpillar poisoning
- Bufencarb
- Bulbar palsy
- Burn injuries
- Butacarb
- Butocarboxim
- Byssinosis
- C1 esterase inhibitor (c1-inh) deficiency
- Cadusafos
- Calcium hypochlorite
- Captafol
- Carbanolate
- Carbaryl
- Carbofuran
- Carbophenothion
- Carbosulfan
- Carcinoid
- Carcinoma of larynx
- Carcinoma of the esophagus
- Carcinoma of the thryoid
- Carcinoma of trachea
- Cardiac failure
- Caustic ingestion
- Cellulitis of neck
- Chlorfenvinphos
- Chlorine dioxide
- Chlorine
- Chloropyrifos
- Choanal atresia
- Chronic lower respiratory diseases
- Chronic obstructive pulmonary disease
- Chronic tuberculous laryngitis
- Classical hodgkin disease
- Cloethocarb
- Common cold
- Compression of bronchii
- Congenital bronchial anomalies
- Congenital laryngeal anomalies
- Congenital laryngeal paralysis in newborns
- Congenital laryngeal stridor
- Congenital subglottic narrowing
- Congenital tracheal anomalies
- Craniofacial anomaly
- Cricoarytenoid ankylosis
- Croup
- Cyanthoate
- Decarbofuran
- Demeton
- Deviated septum
- Dialifos
- Diazinon
- Dichlorvos
- Dicresyl
- Dicrotophos
- Diffuse leiomyomatosis with alport syndrome
- Dimetan
- Dimethoate
- Dimetilan
- Dioxacarb
- Dioxathion
- Diptheria
- Dislocated cricothyroid or cricoarytenoid articulation
- Disulfoton
- Double aortic arch
- Down's syndrome
- Drug allergies
- Edema of the glottis
- Empc
- Endothion
- Enlarged adenoids
- Enlarged tonsils
- Epidermoid carcinoma
- Epiglottitis
- Estrogen dependent hereditary angioedema
- Ethiofencarb
- Ethion
- Ethoate-methyl
- Ethoprophos
- Ethylenediamine
- Ethyl-guthion
- Etrimfos
- Facial fracture
- Fenchlorphos
- Fenethacarb
- Fenitrothion
- Fenobucarb
- Fensulfothion
- Fenthion
- Fonophos
- Food additive allergy
- Food allergies
- Food allergy related asthma
- Foreign body aspiration
- Formaldehyde
- Formothion
- Fresh mangrove caterpillar poisoning
- Furathiocarb
- Gastroesophageal reflux disease
- Gay-feinmesser-cohen syndrome
- Gerhardt syndrome
- Glutaraldehyde
- Goiter
- Granulomatosis with polyangiitis
- Grapeleaf skeletonizer caterpillar poisoning
- Guthion (ethyl)
- Hashimoto's disease
- Hemangioma
- Heptenophos
- Hexamethylene diisocyanate
- Hodgkin's disease
- Hodgkin's lymphoma
- Hydrocephalus
- Hyquincarb
- Idiopathic subglottic tracheal stenosis
- Infectious conditions
- Infectious mononucleosis
- Inhalant abuse
- Inhalation injury
- Inhaled foreign body
- Injury to larynx
- Injury to trachea
- Insect allergy
- Internal laryngeal trauma
- Intrathoracic goitre
- Iodofenphos
- Isoprocarb
- Laryngeal carcinoma
- Laryngeal cleft
- Laryngeal cyst
- Laryngeal fracture
- Laryngeal inflammation
- Laryngeal nerve palsy
- Laryngeal or tracheal abnormalities
- Laryngeal papilloma
- Laryngeal papillomatosis
- Laryngeal stenosis
- Laryngeal web
- Laryngitis
- Laryngocele
- Laryngomalacia
- Laryngoscopy
- Laryngospasm
- Laryngotracheitis
- Laryngotracheobronchitis
- Larynx atresia
- Larynx carcinoma
- Larynx condition
- Latex catheters induced allergies
- Lepidopterism
- Lingual cyst
- Linguinal angioedema
- Local anaesthetic allergy
- Ludwig's angina
- Lung cancer
- Lymphocyte depletion hodgkin's disease
- Macroglossia
- Malathion
- Malignant disease of lower cervical lymph nodes
- Malignant germ cell tumor
- Mandibular fracture
- Mastocytosis
- Maxillo-facial dysplasis
- Mecarbam
- Mediastinal hodgkin's disease
- Mediastinal tumors
- Mesothelioma
- Metabolic disorders
- Metapneumovirus
- Methacrifos
- Methamidophos
- Methidathion
- Methiocarb
- Methomyl
- Metiltriazotion
- Metolcarb
- Mevinphos
- Mexacarbate
- Mixed cellularity hodgkin's disease
- Mixed type non small cell carcinoma
- Monocrotophos
- Morphine allergy
- Nasal polyp
- Nasal septum deviation
- Nasopharyngeal mass
- Neck or facial swelling
- Nerve paresis
- Neural tube defect
- Nickel
- Nitrilacarb
- Nodular goiter
- Nodular sclerosing hodgkin's lymphoma
- Non-small cell lung cancer
- Novacaine drug allergy
- Occupational asthma
- Omethoate
- Osmium
- Oxamyl
- Oxydeprofos
- Oxydisulfoton
- Palladium
- Paragonimiases
- Parathion methyl
- Partial atrioventricular canal
- Peanut allergy
- Penicillin allergy
- Pepper spray
- Peritonsillar abscess
- Phenkapton
- Phorate
- Phosalone
- Phosdrin
- Phosgene oxime
- Phosmet
- Phosphamidon
- Phoxim
- Piriform aperture stenosis
- Pirimicarb
- Pirimiphos-methyl
- Platinum
- Pleura process
- Pneumonia
- Pneumothorax
- Polychondritis
- Post-radiation
- Post-traumatic stenosis of larynx
- Post-traumatic stenosis of the trachea
- Potassium permanganate
- Primary ciliary dyskinesia
- Primiphos methyl
- Profenofos
- Prolonged intubation
- Promacyl
- Promecarb
- Propoxur
- Prothidathion
- Prothoate
- Pseudobulbar palsy
- Psychogenic
- Pulmonary cystic lymphangiectasis
- Pulmonary lymphangiectasia
- Pulmonary pseudolymphoma
- Pyrimitate
- Quinalphos
- Quintiofos
- Recurrent respiratory papillomatosis
- Respiratory tract cancer
- Retropharyngeal abscess
- Retrosternal thyroid
- Rheumatoid disease
- Rhinosinusitis
- Riedel's thyroiditis
- Sarcoidosis
- Satin moth caterpillar poisoning
- Scar stenosis
- Seafood allergy
- Secretions
- Shy-drager syndrome
- Silver
- Small cell lung cancer
- Small jaw
- Smokers throat
- Smoking cessation
- Sophamide
- Spasmodic croup
- Spice allergy
- Sputum
- Squamous cell carcinoma
- Stinging bark caterpillar poisoning
- Stinging nettle caterpillar poisoning
- Stinging rose caterpillar poisoning
- Strictures of main bronchi in sarcoidosis
- Subglottic hemangioma
- Subglottic stenosis
- Sulfa antibiotics allergy
- Sulfotep
- Sulfur trioxide
- Supraglottic webs
- Syphilis
- Syphilitic laryngitis with stenosis
- Tacrine toxicity
- Tazimcarb
- Terbufos
- Tetraethyl pyrophosphate
- Thiocarboxime
- Thiodicarb
- Thiofanox
- Thiometon
- Thoracic aortic aneurysm
- Thymic epithelial tumor
- Thyroglossic cyst
- Thyroidectomy
- Tolclofos methyl
- Tonsillitis
- Tracheal cancer
- Tracheal intubation
- Tracheal stenosis
- Tracheobronchomalacia
- Tracheobronchopathia osteoplastica
- Tracheolaryngobronchitis
- Tracheomalacia
- Tracheopathia osteoplastica
- Tracheostomy
- Trachiobronchitis
- Transfusion reaction
- Trauma
- Triazophos
- Triazotion
- Trifenfos
- Trimellitic anhydride
- Trimethacarb
- Tuberculin
- Tuberculosis
- Tuberculous nodes in mediastinum
- Tuberculous strictures of main bronchi
- Tumor infiltration
- Upper airway burns
- Uranium
- Vamidothion
- Vanadium toxicity
- Vanadium
- Vascular rings
- Vasculitis
- Vocal cord cancer
- Vocal cord paralysis
- Weeping fig poisoning
- Wegener's granulomatosis
- Xmc
- Xylylcarb
# Treatments
The first issue of clinical concern in the setting of stridor is whether or not tracheal intubation or tracheostomy is immediately necessary. Some patients will need immediate tracheal intubation. If intubation can be delayed for a period a number of other potential options can be considered, depending on the severity of the situation and other clinical details. These include:
- Expectant management with full monitoring, oxygen by face mask, and positioning the head of the bed for optimum conditions (e.g., 45 - 90 degrees)
- Use of nebulized racemic epinephrine (0.5 to 0.75 ml of 2.25% racemic epinephrine added to 2.5 to 3 ml of normal saline) in cases where airway edema may be the cause of the stridor. ( Nebulized Cocaine in a dose not exceeding 3 mg/kg may also be used, but not together with racemic epinephrine [because of the risk of ventricular arrhythmias].)
- Use of dexamethasone (Decadron) 4-8 mg IV q 8 - 12 h in cases where airway edema may be the cause of the stridor; note that some time (in the range of hours) may be need for dexamethasone to work fully.
- Use of inhaled Heliox (70% helium, 30% oxygen); the effect is almost instantaneous
# Diagnosis
Stridor is usually diagnosed the basis of history and physical examination, with a view to revealing the underlying problem or condition.
Chest and neck x-rays, CT-scans, and / or MRIs may reveal structural pathology.
Flexible fiberoptic bronchoscopy can also be very helpful, especially in assessing vocal cord function of in looking for signs of compression or infection. | https://www.wikidoc.org/index.php/Ddx:Stridor | |
08a9a7235e54d73102184e4375367fbeffe8b92d | wikidoc | Thiamin | Thiamin
# Overview
Thiamin or thiamine, also known as vitamin B1 and aneurine hydrochloride, is one of the B vitamins. It is colorless chemical compound with a chemical formula C12H17N4OS. It is soluble in water, methanol, and glycerol and practically insoluble in acetone, ether, chloroform, and benzene. Thiamin decomposes if heated. Its chemical structure contains a pyrimidine ring and a thiazole ring.
Thiamin is essential for neural function and carbohydrate metabolism. A severe thiamin deficiency results in Beriberi which is a nerve and heart disease. In less severe deficiency, nonspecific signs include malaise, weight loss, irritability and confusion.
# History
Thiamin was first discovered in 1910 by Umetaro Suzuki in Japan when researching how rice bran cured patients of beriberi. He named it aberic acid (later oryzanin). He did not determine its chemical composition, nor that it was an amine. It was first crystallized by Jansen and Donath in 1926 (they named it aneurin, for antineuritic vitamin). Its chemical composition and synthesis was finally reported by Robert R. Williams in 1935. He also coined the current name for it, thiamine.
# Sources
Thiamin is found in a wide variety of many foods at low concentrations. While yeast and liver are the most highly concentrated sources of thiamin, these foods are not commonly consumed in the American diet. Cereal grains, however, are the most important dietary sources of thiamin in the diet as these foods are consumed readily in most diets. Of the cereal grains, whole grains contain more thiamin than refined grains. Thiamin is found in the outer layers of the grain as well as the germ. During the refining process these segments of the grain are removed therefore decreasing the thiamin content in products such as white rice and white bread. For example, 100 g of whole wheat flour contains 0.55 mg of thiamin while 100 g of white flour only contains 0.06 mg of thiamin. In addition to cereal grains some vegetables and meats are also good sources of thiamin. Listed below are foods rich in thiamin.
- Yeast
- Oatmeal
- Brown rice
- Whole grain flour (rye or wheat)
- Peas
- Asparagus
- Kale
- Cauliflower
- Potatoes
- Oranges
- Pork
- Cured ham
- Liver (beef or pork)
- Eggs
# Antagonists
Thiamin in foods can be degraded in a variety of ways. Sulfites, which are added to foods usually as a preservative, will attack thiamin at the methylene bridge in the structure, cleaving the pyrimidine ring from the thiazole ring. The rate of this reaction is increased under acidic conditions. Thiamin can also be degraded by thiaminases. Some thiaminases are produced by bacteria. Bacterial thiaminases are cell surface enzymes that must dissociate from the membrane before being activated. The dissociation can occur in ruminants under acidotic conditions. Rumen bacteria also reduce sulfate to sulfite, therefore high dietary intakes of sulfate can have thiamin-antagonistic activities.
Plant thiamin antagonists are heat stable and occur as both the ortho and para hydroxyphenols. Some examples of these antagonists are caffeic acid, chlorogenic acid and tannic acid. These compounds interact with the thiamin to oxidize the thiazole ring, thus rendering it unable to be absorbed. Two flavonoids, quercetin and rutin, have also been implicated as thiamin antagonists.
# Absorption
Thiamin is released by the action of phosphatase and pyrophosphatase in the upper small intestine. At low concentrations the process is carrier mediated and at higher concentrations, absorption occurs via passive diffusion. Active transport is greatest in the jejunum and ileum. The cells of the intestinal mucosa have thiamin pyrophosphokinase activity, but it is unclear whether the enzyme is linked to active absorption. The majority of thiamin present in the intestine is in the phosphorylated form, but when thiamine arrives on the serosal side of the intestine it is often in the free form. The uptake of thiamine by the mucosal cell is likely coupled in some way to its phosphorylation/dephosphorylation. On the serosal side of the intestine, evidence has shown that discharge of the vitamin by those cells is dependent on Na+-dependent ATPase.
# Transport
### Bound to serum proteins
The majority of thiamin in serum is bound to proteins, mainly albumin. Approximately 90% of total thiamin in blood is in erythrocytes. A specific binding protein called thiamin-binding protein (TBP) has been identified in rat serum and is believed to be a hormonally regulated carrier protein that is important for tissue distribution of thiamin.
### Cellular uptake
Uptake of thiamin by cells of the blood and other tissues occurs via active transport. About 80% of intracellular thiamin is phosphorylated and most is bound to proteins. In some tissues, thiamin uptake and secretion appears to be mediated by a soluble thiamin transporter that is dependent on Na+ and a transcellular proton gradient. The highest concentration of the transporter have been found in skeletal muscle, heart, and placenta.
## Tissue Distribution
Human storage of thiamin is about 25 to 30 mg with the greatest concentrations in skeletal muscle, heart, brain, liver, and kidneys. Thiamin monophosphate(TMP) and free thiamin is present in plasma, milk, cerebrospinal fluid, and likely all extracellular fluids. Unlike the highly phosphorylated forms of thiamin, TMP and free thiamin are capable of crossing cell membranes. Thiamin contents in human tissues are less than those of other species.
# Deficiency
Systemic thiamin deficiency can lead to myriad problems including neurodegeneration, wasting and death. A lack of thiamin can be caused by malnutrition, alcoholism, a diet high in thiaminase-rich foods (raw freshwater fish, raw shellfish, ferns) and/or foods high in anti-thiamine factors (tea, coffee, betel nuts).
Well-known syndromes caused by thiamin deficiency include Wernicke-Korsakoff syndrome and beriberi, diseases also common with chronic alcoholism.
Polioencephalomalacia (PEM), is the most common thiamin deficiency disorder in young ruminant and nonruminant animals. Symptoms of PEM include a profuse, but transient diarrhea, listlessness, circling movements, star gazing or opisthotonus (head drawn back over neck), and muscle tremors.
It is thought that many people with diabetes have a deficiency of thiamin and that this may be linked to some of the complications that can occur.
### Alcoholic Brain Disease
Thiamin and thiamin-using enzymes are present in all cells of the body, thus, a thiamin deficiency would seem to adversely affect all of the organ systems. However, the nervous system (and heart) shows particular sensitivity to the effects of a thiamin deficiency at the cellular level.
Nerve cells and other supporting cells (such as glial cells) of the nervous system require thiamin. Examples of neurologic disorders that are linked to alcohol abuse include Wernicke’s Encephalopathy (Wernicke-Korsakoff’s syndrome) and Korsakoff’s psychosis (alcohol amnestic disorder) as well as varying degrees of cognitive impairment.
How does alcoholism induce thiamin deficiency? The enzymes transketolase, pyruvate dehydrogenase (PDH) and alpha-ketoglutarate dehydrogenase (α-KGDH) all require thiamin as a cofactor in order to function in carbohydrate metabolism. Therefore, a thiamin deficiency would be detrimental to the functionality of these enzymes. Transketolase is important in the pentose phosphate pathway. PDH and α-KGDH function in biochemical pathways that result in the generation of adenosine triphosphate (ATP), which is a major form of energy for the cell. PDH is also needed for the production of acetylcholine, a neurotransmitter, and for myelin synthesis. During metabolism, PDH determines whether the process is aerobic or anaerobic, and α-KGDH is responsible for determining the rate of the citric acid cycle.
What are the mechanisms of alcohol-induced thiamin deficiency?
1) Inadequate nutritional intake: Alcoholics tend to intake less than the recommended amount of thiamin, however it is also seen that others have an extremely high level of free thiamin, suggesting an inability of these individuals to convert thiamin to the biologically active, phosphorylated form.
2) Decreased uptake of thiamin from the GI tract: Active transport of thiamin into the enterocyte occurs mostly in conditions of low thiamin concentration. The absorption is disturbed during acute alcohol exposure as illustrated by less thiamin being converted into the phosphate-containing form, suggesting a dysfunction of the enzyme responsible for this transformation: thiamin diphosphokinase.
3) Impaired thiamin utilization: Magnesium, which is required for the binding of thiamin to thiamin-using enzymes within the cell, is also deficient due to chronic alcohol consumption. The inefficient utilization of any thiamin that does reach the cells will further exacerbate the thiamin deficiency.
Following improved nutrition and the removal of alcohol consumption, some impairments linked with thiamin deficiency are reversed; particularly poor brain functionality.
# Diagnostic testing
A positive diagnosis test for thiamine deficiency can be ascertained by measuring the activity of the enzyme transketolase in erythrocytes. Thiamine can also be seen directly in whole blood following the conversion of thiamine to a fluorescent thiochrome derivative. However, this test may not reveal the deficiency in diabetic patients.
# Thiamine phosphate derivatives
There are four known natural thiamine phosphate derivatives: thiamine monophosphate (ThMP), thiamine diphosphate (ThDP) or thiamine pyrophosphate (TPP), thiamine triphosphate (ThTP), and the recently discovered adenosine thiamine triphosphate (AThTP).
### Thiamine pyrophosphate
Thiamine pyrophosphate (TPP), also known as thiamin diphosphate (ThDP), and cocarboxylase is a coenzyme for several enzymes that catalyze the dehydrogenation (decarboxylation and subsequent conjugation to Coenzyme A) of alpha-keto acids. Examples include:
- In mammals:
pyruvate dehydrogenase and α-ketoglutarate dehydrogenase (metabolism of carbohydrates)
branched-chain alpha-keto acid dehydrogenase
2-hydroxyphytanoyl-CoA lyase
transketolase (functions in the pentose phosphate pathway to synthesize NADPH and the pentose sugars deoxyribose and ribose )
- pyruvate dehydrogenase and α-ketoglutarate dehydrogenase (metabolism of carbohydrates)
- branched-chain alpha-keto acid dehydrogenase
- 2-hydroxyphytanoyl-CoA lyase
- transketolase (functions in the pentose phosphate pathway to synthesize NADPH and the pentose sugars deoxyribose and ribose )
- In other species:
pyruvate decarboxylase (in yeast)
several additional bacterial enzymes
- pyruvate decarboxylase (in yeast)
- several additional bacterial enzymes
TPP is synthesized by the enzyme thiamin pyrophosphokinase, which requires free thiamin, magnesium, and adenosine triphosphate.
### Thiamine triphosphate
Thiamine triphosphate (ThTP) was long considered a specific neuroactive form of thiamin. However, recently it was shown that ThTP exists in bacteria, fungi, plants and animals suggesting a much more general cellular role. In particular in E. coli it seems to play a role in response to amino acid starvation.
### Adenosine thiamine triphosphate
Adenosine thiamine triphosphate (AThTP) or thiaminylated adenosine triphosphate has recently been discovered in Escherichia coli where it accumulates as a result of carbon starvation. In E. coli, AThTP may account for up to 20 % of total thiamin. It also exists in lesser amounts in yeast, roots of higher plants and animal tissues.
# Genetic diseases
Genetic diseases of thiamin transport are rare but serious. Thiamin Responsive Megaloblastic Anemia with diabetes mellitus and sensorineural deafness (TRMA) is an autosomal recessive disorder caused by mutations in the gene SLC19A2, a high affinity thiamine transporter. TRMA patients do not show signs of systemic thiamin deficiency, suggesting redundancy in the thiamin transport system. This has led to the discovery of a second high affinity thiamin transporter, SLC19A3.
# Research
### High doses
The RDA in most countries is set at about 1.4 mg. However, tests on volunteers at daily doses of about 50 mg have claimed an increase in mental acuity.
### Thiamin as an insect repellent
Some studies suggest that taking thiamin 25 to 50 mg three times per day is effective in reducing mosquito bites. A large intake of thiamin produces a skin odor that is not detectable by humans, but is disagreeable to female mosquitoes. Thiamin takes more than 2 weeks before the odor fully saturates the skin. With the advances in topical preparations there is an increasing number of thiamin based repellent products. There is anecdotal evidence of thiamin products being effective in the field (Australia, US and Canada), but one study found thiamin had no effect.
### Autism
A 2002 pilot study administered thiamin tetrahydrofurfuryl disulfide (TTFD) rectally to ten autism spectrum children, and found beneficial clinical effect in eight. This study has not been replicated and a 2006 review of thiamin by the same author did not mention thiamin's possible effect on autism.
# Differential Diagnosis
- Dialysis
- Diuresis
- Hodgkin's Lymphoma
- Insufficient supply
- Increased demand
- Leukemia
- Malabsorbtion
- Maldigestion
- Polycythemia | Thiamin
Template:Chembox new
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Thiamin or thiamine, also known as vitamin B1 and aneurine hydrochloride, is one of the B vitamins. It is colorless chemical compound with a chemical formula C12H17N4OS. It is soluble in water, methanol, and glycerol and practically insoluble in acetone, ether, chloroform, and benzene. Thiamin decomposes if heated. Its chemical structure contains a pyrimidine ring and a thiazole ring.
Thiamin is essential for neural function and carbohydrate metabolism. A severe thiamin deficiency results in Beriberi which is a nerve and heart disease. In less severe deficiency, nonspecific signs include malaise, weight loss, irritability and confusion.[1]
# History
Thiamin was first discovered in 1910 by Umetaro Suzuki in Japan when researching how rice bran cured patients of beriberi. He named it aberic acid (later oryzanin). He did not determine its chemical composition, nor that it was an amine. It was first crystallized by Jansen and Donath in 1926 (they named it aneurin, for antineuritic vitamin). Its chemical composition and synthesis was finally reported by Robert R. Williams in 1935. He also coined the current name for it, thiamine.
# Sources
Thiamin is found in a wide variety of many foods at low concentrations. While yeast and liver are the most highly concentrated sources of thiamin, these foods are not commonly consumed in the American diet. Cereal grains, however, are the most important dietary sources of thiamin in the diet as these foods are consumed readily in most diets. Of the cereal grains, whole grains contain more thiamin than refined grains. Thiamin is found in the outer layers of the grain as well as the germ. During the refining process these segments of the grain are removed therefore decreasing the thiamin content in products such as white rice and white bread. For example, 100 g of whole wheat flour contains 0.55 mg of thiamin while 100 g of white flour only contains 0.06 mg of thiamin. In addition to cereal grains some vegetables and meats are also good sources of thiamin. Listed below are foods rich in thiamin.[2]
- Yeast
- Oatmeal
- Brown rice
- Whole grain flour (rye or wheat)
- Peas
- Asparagus
- Kale
- Cauliflower
- Potatoes
- Oranges
- Pork
- Cured ham
- Liver (beef or pork)
- Eggs
# Antagonists
Thiamin in foods can be degraded in a variety of ways. Sulfites, which are added to foods usually as a preservative,[3] will attack thiamin at the methylene bridge in the structure, cleaving the pyrimidine ring from the thiazole ring.[4] The rate of this reaction is increased under acidic conditions. Thiamin can also be degraded by thiaminases. Some thiaminases are produced by bacteria. Bacterial thiaminases are cell surface enzymes that must dissociate from the membrane before being activated. The dissociation can occur in ruminants under acidotic conditions. Rumen bacteria also reduce sulfate to sulfite, therefore high dietary intakes of sulfate can have thiamin-antagonistic activities.
Plant thiamin antagonists are heat stable and occur as both the ortho and para hydroxyphenols. Some examples of these antagonists are caffeic acid, chlorogenic acid and tannic acid. These compounds interact with the thiamin to oxidize the thiazole ring, thus rendering it unable to be absorbed. Two flavonoids, quercetin and rutin, have also been implicated as thiamin antagonists.[5]
# Absorption
Thiamin is released by the action of phosphatase and pyrophosphatase in the upper small intestine. At low concentrations the process is carrier mediated and at higher concentrations, absorption occurs via passive diffusion. Active transport is greatest in the jejunum and ileum. The cells of the intestinal mucosa have thiamin pyrophosphokinase activity, but it is unclear whether the enzyme is linked to active absorption. The majority of thiamin present in the intestine is in the phosphorylated form, but when thiamine arrives on the serosal side of the intestine it is often in the free form. The uptake of thiamine by the mucosal cell is likely coupled in some way to its phosphorylation/dephosphorylation. On the serosal side of the intestine, evidence has shown that discharge of the vitamin by those cells is dependent on Na+-dependent ATPase.[6]
# Transport
### Bound to serum proteins
The majority of thiamin in serum is bound to proteins, mainly albumin. Approximately 90% of total thiamin in blood is in erythrocytes. A specific binding protein called thiamin-binding protein (TBP) has been identified in rat serum and is believed to be a hormonally regulated carrier protein that is important for tissue distribution of thiamin.[7]
### Cellular uptake
Uptake of thiamin by cells of the blood and other tissues occurs via active transport. About 80% of intracellular thiamin is phosphorylated and most is bound to proteins. In some tissues, thiamin uptake and secretion appears to be mediated by a soluble thiamin transporter that is dependent on Na+ and a transcellular proton gradient. The highest concentration of the transporter have been found in skeletal muscle, heart, and placenta.[8]
## Tissue Distribution
Human storage of thiamin is about 25 to 30 mg with the greatest concentrations in skeletal muscle, heart, brain, liver, and kidneys. Thiamin monophosphate(TMP) and free thiamin is present in plasma, milk, cerebrospinal fluid, and likely all extracellular fluids. Unlike the highly phosphorylated forms of thiamin, TMP and free thiamin are capable of crossing cell membranes. Thiamin contents in human tissues are less than those of other species.[9]
# Deficiency
Systemic thiamin deficiency can lead to myriad problems including neurodegeneration, wasting and death. A lack of thiamin can be caused by malnutrition, alcoholism, a diet high in thiaminase-rich foods (raw freshwater fish, raw shellfish, ferns) and/or foods high in anti-thiamine factors (tea, coffee, betel nuts).[10]
Well-known syndromes caused by thiamin deficiency include Wernicke-Korsakoff syndrome and beriberi, diseases also common with chronic alcoholism.
Polioencephalomalacia (PEM), is the most common thiamin deficiency disorder in young ruminant and nonruminant animals. Symptoms of PEM include a profuse, but transient diarrhea, listlessness, circling movements, star gazing or opisthotonus (head drawn back over neck), and muscle tremors.[11]
It is thought that many people with diabetes have a deficiency of thiamin and that this may be linked to some of the complications that can occur.[12][13]
### Alcoholic Brain Disease[14]
Thiamin and thiamin-using enzymes are present in all cells of the body, thus, a thiamin deficiency would seem to adversely affect all of the organ systems. However, the nervous system (and heart) shows particular sensitivity to the effects of a thiamin deficiency at the cellular level.
Nerve cells and other supporting cells (such as glial cells) of the nervous system require thiamin. Examples of neurologic disorders that are linked to alcohol abuse include Wernicke’s Encephalopathy (Wernicke-Korsakoff’s syndrome) and Korsakoff’s psychosis (alcohol amnestic disorder) as well as varying degrees of cognitive impairment.
How does alcoholism induce thiamin deficiency? The enzymes transketolase, pyruvate dehydrogenase (PDH) and alpha-ketoglutarate dehydrogenase (α-KGDH) all require thiamin as a cofactor in order to function in carbohydrate metabolism. Therefore, a thiamin deficiency would be detrimental to the functionality of these enzymes. Transketolase is important in the pentose phosphate pathway. PDH and α-KGDH function in biochemical pathways that result in the generation of adenosine triphosphate (ATP), which is a major form of energy for the cell. PDH is also needed for the production of acetylcholine, a neurotransmitter, and for myelin synthesis. During metabolism, PDH determines whether the process is aerobic or anaerobic, and α-KGDH is responsible for determining the rate of the citric acid cycle.
What are the mechanisms of alcohol-induced thiamin deficiency?
1) Inadequate nutritional intake: Alcoholics tend to intake less than the recommended amount of thiamin, however it is also seen that others have an extremely high level of free thiamin, suggesting an inability of these individuals to convert thiamin to the biologically active, phosphorylated form.
2) Decreased uptake of thiamin from the GI tract: Active transport of thiamin into the enterocyte occurs mostly in conditions of low thiamin concentration. The absorption is disturbed during acute alcohol exposure as illustrated by less thiamin being converted into the phosphate-containing form, suggesting a dysfunction of the enzyme responsible for this transformation: thiamin diphosphokinase.
3) Impaired thiamin utilization: Magnesium, which is required for the binding of thiamin to thiamin-using enzymes within the cell, is also deficient due to chronic alcohol consumption. The inefficient utilization of any thiamin that does reach the cells will further exacerbate the thiamin deficiency.
Following improved nutrition and the removal of alcohol consumption, some impairments linked with thiamin deficiency are reversed; particularly poor brain functionality.
# Diagnostic testing
A positive diagnosis test for thiamine deficiency can be ascertained by measuring the activity of the enzyme transketolase in erythrocytes. Thiamine can also be seen directly in whole blood following the conversion of thiamine to a fluorescent thiochrome derivative. However, this test may not reveal the deficiency in diabetic patients.[12][15]
# Thiamine phosphate derivatives
There are four known natural thiamine phosphate derivatives: thiamine monophosphate (ThMP), thiamine diphosphate (ThDP) or thiamine pyrophosphate (TPP), thiamine triphosphate (ThTP), and the recently discovered adenosine thiamine triphosphate (AThTP).
### Thiamine pyrophosphate
Thiamine pyrophosphate (TPP), also known as thiamin diphosphate (ThDP), and cocarboxylase is a coenzyme for several enzymes that catalyze the dehydrogenation (decarboxylation and subsequent conjugation to Coenzyme A) of alpha-keto acids. Examples include:
- In mammals:
pyruvate dehydrogenase and α-ketoglutarate dehydrogenase (metabolism of carbohydrates)
branched-chain alpha-keto acid dehydrogenase
2-hydroxyphytanoyl-CoA lyase
transketolase (functions in the pentose phosphate pathway to synthesize NADPH and the pentose sugars deoxyribose and ribose )
- pyruvate dehydrogenase and α-ketoglutarate dehydrogenase (metabolism of carbohydrates)
- branched-chain alpha-keto acid dehydrogenase
- 2-hydroxyphytanoyl-CoA lyase
- transketolase (functions in the pentose phosphate pathway to synthesize NADPH and the pentose sugars deoxyribose and ribose )
- In other species:
pyruvate decarboxylase (in yeast)
several additional bacterial enzymes
- pyruvate decarboxylase (in yeast)
- several additional bacterial enzymes
TPP is synthesized by the enzyme thiamin pyrophosphokinase, which requires free thiamin, magnesium, and adenosine triphosphate.
### Thiamine triphosphate
Thiamine triphosphate (ThTP) was long considered a specific neuroactive form of thiamin. However, recently it was shown that ThTP exists in bacteria, fungi, plants and animals suggesting a much more general cellular role. In particular in E. coli it seems to play a role in response to amino acid starvation.
### Adenosine thiamine triphosphate
Adenosine thiamine triphosphate (AThTP) or thiaminylated adenosine triphosphate has recently been discovered in Escherichia coli where it accumulates as a result of carbon starvation. In E. coli, AThTP may account for up to 20 % of total thiamin. It also exists in lesser amounts in yeast, roots of higher plants and animal tissues.
# Genetic diseases
Genetic diseases of thiamin transport are rare but serious. Thiamin Responsive Megaloblastic Anemia with diabetes mellitus and sensorineural deafness (TRMA)[16] is an autosomal recessive disorder caused by mutations in the gene SLC19A2,[17] a high affinity thiamine transporter. TRMA patients do not show signs of systemic thiamin deficiency, suggesting redundancy in the thiamin transport system. This has led to the discovery of a second high affinity thiamin transporter, SLC19A3.[18][19]
# Research
### High doses
The RDA in most countries is set at about 1.4 mg. However, tests on volunteers at daily doses of about 50 mg have claimed an increase in mental acuity.[20]
### Thiamin as an insect repellent
Some studies suggest that taking thiamin 25 to 50 mg three times per day is effective in reducing mosquito bites. A large intake of thiamin produces a skin odor that is not detectable by humans, but is disagreeable to female mosquitoes.[21] Thiamin takes more than 2 weeks before the odor fully saturates the skin. With the advances in topical preparations there is an increasing number of thiamin based repellent products. There is anecdotal evidence of thiamin products being effective in the field (Australia, US and Canada), but one study found thiamin had no effect.[22]
### Autism
A 2002 pilot study administered thiamin tetrahydrofurfuryl disulfide (TTFD) rectally to ten autism spectrum children, and found beneficial clinical effect in eight.[23] This study has not been replicated and a 2006 review of thiamin by the same author did not mention thiamin's possible effect on autism.[24]
# Differential Diagnosis
- Dialysis
- Diuresis
- Hodgkin's Lymphoma
- Insufficient supply
- Increased demand
- Leukemia
- Malabsorbtion
- Maldigestion
- Polycythemia | https://www.wikidoc.org/index.php/Ddx:Vitamin_B1 | |
37f8afe39083948181c3e16c5908f18f95c86288 | wikidoc | Decibel | Decibel
The decibel (dB) is a logarithmic unit of measurement that expresses the magnitude of a physical quantity (usually power or intensity) relative to a specified or implied reference level. Since it expresses a ratio of two (same unit) quantities, it is a dimensionless unit. A decibel is one tenth of a bel (B).
The decibel is useful for a wide variety of measurements in science and engineering (e.g., acoustics and electronics) and other disciplines. It confers a number of advantages, such as the ability to conveniently represent very large or small numbers, a logarithmic scaling that roughly corresponds to the human perception of, for example, sound and light, and the ability to carry out multiplication of ratios by simple addition and subtraction.
The decibel is not an SI unit. However, following the SI convention, the d is lowercase, as it represents the SI prefix deci-, and the B is capitalized, as it is an abbreviation of a name-derived unit (the bel). The full name decibel follows the usual English capitalization rules for a common noun.
The decibel symbol is often qualified with a suffix, which indicates which reference quantity or frequency weighting function has been used. For example, "dBm" indicates that the reference quantity is one milliwatt, while "dBu" is referenced to 0.775 volts. The practice of attaching a suffix in this way, though not permitted by SI, is widely followed.
The definitions of the decibel and bel use base-10 logarithms. For a similar unit using natural logarithms to base e, see neper.
# History
The bel was originally devised by engineers of the Bell Telephone Laboratories to quantify the reduction in audio level over a 1 mile (approximately 1.6 km) length of standard telephone cable. It was originally called the transmission unit or TU, but was renamed in 1923 or 1924 in honor of the Bell System's founder and telecommunications pioneer Alexander Graham Bell. In many situations, however, the bel proved inconveniently large, so the decibel has become more common.
In April 2003, the International Committee for Weights and Measures (CIPM) considered a recommendation for the decibel's inclusion in the SI system, but decided not to adopt the decibel as an SI unit.
# Definitions
## Power
When referring to measurements of power or intensity, a ratio can be expressed in decibels by evaluating ten times the base-10 logarithm of the ratio of the measured quantity to the reference level. Thus, if L represents the ratio of a power value P1 to another power value P0, then LdB represents that ratio expressed in decibels and is calculated using the formula:
L_\mathrm{dB} = 10 \log_{10} \bigg(\frac{P_1}{P_0}\bigg) \,
Naturally, P1 and P0 must have the same dimension (that is, must measure the same type of quantity), and must as necessary be converted to the same units before calculating the ratio of their numerical values. Note that if P1 = P0 in the above equation, then LdB = 0. If P1 is greater than P0 then LdB is positive; if P1 is less than P0 then LdB is negative.
Rearranging the above equation gives the following formula for P1 in terms of P0 and LdB:
P_1 = 10^\frac{L_\mathrm{dB}}{10} P_0 \,
Since a bel is equal to ten decibels, the corresponding formulae for measurement in bels (LB) are
L_\mathrm{B} = \log_{10} \bigg(\frac{P_1}{P_0}\bigg) \,
P_1 = 10^{L_\mathrm{B}} P_0 \,
## Amplitude, voltage and current
When referring to measurements of amplitude it is usual to consider the ratio of the squares of A1 (measured amplitude) and A0 (reference amplitude). This is because in most applications power is proportional to the square of amplitude. Thus the following definition is used:
L_\mathrm{dB} = 10 \log_{10} \bigg(\frac{A_1^2}{A_0^2}\bigg) = 20 \log_{10} \bigg(\frac{A_1}{A_0}\bigg) \,
The formula may be rearranged to give
A_1 = 10^\frac{L_\mathrm{dB}}{20} A_0 \,
Similarly, in electrical circuits, dissipated power is typically proportional to the square of voltage or current when the impedance is held constant. Taking voltage as an example, this leads to the equation:
G_\mathrm{dB} =20 \log_{10} \left (\frac{V_1}{V_0} \right ) \quad \mathrm \quad
where V1 is the voltage being measured, V0 is a specified reference voltage, and GdB is the power gain expressed in decibels. A similar formula holds for current.
## Examples
Note that all of these examples yield dimensionless answers in dB because they are relative ratios expressed in decibels.
- To calculate the ratio of 1 kW (one kilowatt, or 1000 watts) to 1 W in decibels, use the formula
G_\mathrm{dB} = 10 \log_{10} \bigg(\frac{1000 \mathrm{W}}{1 \mathrm{W}}\bigg) = 30 \mathrm{dB} \,
- To calculate the ratio of 1 mW (one milliwatt) to 10 W in decibels, use the formula
G_\mathrm{dB} = 10 \log_{10} \bigg(\frac{.001 \mathrm{W}}{10 \mathrm{W}}\bigg) = -40 \mathrm{dB} \,
- To find the power ratio corresponding to a 3 dB change in level, use the formula
G = 10^\frac{3}{10} \times 1\ = 1.99526... \approx 2 \,
It is seen that there is a 10 dB increase (decrease) for each factor 10 increase (decrease) in the ratio of the two power levels, and approximately a 3 dB increase (decrease) for every factor 2 increase (decrease). In exact terms, the factor is 103/10, or 1.9953, about 0.24% different from exactly 2. Similarly, an increase of 3 dB implies an increase in voltage by a factor of approximately √2, or about 1.41, an increase of 6 dB corresponds to approximately four times the power and twice the voltage, and so on. (In exact terms the power factor is 106/10, or about 3.9811, a relative error of about 0.5%.)
# Merits
The use of the decibel has a number of merits:
- The decibel's logarithmic nature means that a very large range of ratios can be represented by a convenient number, in a similar manner to scientific notation. This allows one to clearly visualize huge changes of some quantity. (See Bode Plot and half logarithm graph.)
- The mathematical properties of logarithms mean that the overall decibel gain of a multi-component system (such as consecutive amplifiers) can be calculated simply by summing the decibel gains of the individual components, rather than needing to multiply amplification factors. Essentially this is because log(A × B × C × ...) = log(A) + log(B) + log(C) + ...
- The human perception of, for example, sound or light, is, roughly speaking, such that a doubling of actual intensity causes perceived intensity to always increase by the same amount, irrespective of the original level. The decibel's logarithmic scale, in which a doubling of power or intensity always causes an increase of approximately 3 dB, corresponds to this perception.
# Uses
## Acoustics
The decibel is commonly used in acoustics to quantify sound levels relative to some 0 dB reference. The reference level is typically set at the threshold of perception of an average human and there are common comparisons used to illustrate different levels of sound pressure.
A reason for using the decibel is that the ear is capable of detecting a very large range of sound pressures. The ratio of the sound pressure that causes permanent damage from short exposure to the limit that (undamaged) ears can hear is above a million. Because the power in a sound wave is proportional to the square of the pressure, the ratio of the maximum power to the minimum power is above one (short scale) trillion. To deal with such a range, logarithmic units are useful: the log of a trillion is 12, so this ratio represents a difference of 120 dB. Since the human ear is not equally sensitive to all the frequencies of sound within the entire spectrum, noise levels at maximum human sensitivity — for example, the higher harmonics of middle A (between 2 and 4 kHz) — are factored more heavily into sound descriptions using a process called frequency weighting.
## Electronics
In electronics, the decibel is often used to express power or amplitude ratios (gains), in preference to arithmetic ratios or percentages. One advantage is that the total decibel gain of a series of components (such as amplifiers and attenuators) can be calculated simply by summing the decibel gains of the individual components. Similarly, in telecommunications, decibels are used to account for the gains and losses of a signal from a transmitter to a receiver through some medium (free space, wave guides, coax, fiber optics, etc.) using a link budget.
The decibel unit can also be combined with a suffix to create an absolute unit of electric power. For example, it can be combined with "m" for "milliwatt" to produce the "dBm". Zero dBm is the power level corresponding to a power of one milliwatt, and 1 dBm is one decibel greater (about 1.259 mW).
In professional audio, a popular unit is the dBu (see below for all the units). The "u" stands for "unloaded", and was probably chosen to be similar to lowercase "v", as dBv was the older name for the same thing. It was changed to avoid confusion with dBV. This unit (dBu) is an RMS measurement of voltage which uses as its reference 0.775 VRMS. Chosen for historical reasons, it is the voltage level which delivers 1 mW of power in a 600 ohm resistor, which used to be the standard reference impedance in almost all professional low-impedance audio circuits.
The bel is used to represent noise power levels in hard drive specifications. It shares the same symbol (B) as the byte.
## Optics
In an optical link, if a known amount of optical power, in dBm (referenced to 1 mW), is launched into a fiber, and the losses, in dB (decibels), of each electronic component (e.g., connectors, splices, and lengths of fiber) are known, the overall link loss may be quickly calculated by addition and subtraction of decibel quantities.
In spectrometry and optics, the blocking unit used to measure optical density is equivalent to −1 B. In astronomy, the apparent magnitude measures the brightness of a star logarithmically, since, just as the ear responds logarithmically to acoustic power, the eye responds logarithmically to brightness; however astronomical magnitudes reverse the sign with respect to the bel, so that the brightest stars have the lowest magnitudes, and the magnitude increases for fainter stars.
# Common reference levels and corresponding units
## "Absolute" and "relative" decibel measurements
Although decibel measurements are always relative to a reference level, if the numerical value of that reference is explicitly and exactly stated, then the decibel measurement is called an "absolute" measurement, in the sense that the exact value of the measured quantity can be recovered using the formula given earlier. For example, since dBm indicates power measurement relative to 1 milliwatt,
- 0 dBm means no change from 1 mW. Thus, 0 dBm is the power level corresponding to a power of exactly 1 mW.
- 3 dBm means 3 dB greater than 0 dBm. Thus, 3 dBm is the power level corresponding to 103/10 × 1 mW, or approximately 2 mW.
- −6 dBm means 6 dB less than 0 dBm. Thus, −6 dBm is the power level corresponding to 10−6/10 × 1 mW, or approximately 250 μW (0.25 mW).
If the numerical value of the reference is not explicitly stated, as in the dB gain of an amplifier, then the decibel measurement is purely relative. The practice of attaching a suffix to the basic dB unit, forming compound units such as dBm, dBu, dBA, etc, is not permitted by SI. However, outside of documents adhering to SI units, the practice is very common as illustrated by the following examples.
## Absolute measurements
### Electric power
dBm or dBmW
dBW
### Voltage
Note that the decibel has a different definition when applied to voltage (as contrasted with power). See the "Definitions" section above.
dBV
dBu or dBv
dBmV
dBμV or dBuV
### Acoustics
dB(SPL)
dB SIL
dB SWL
dB(A), dB(B), and dB(C)
dB HL or dB hearing level is used in Audiograms as a measure of hearing loss. The reference level varies with frequency according to a Minimum audibility curve as defined in ANSI and other standards, such that the resulting audiogram shows deviation from what is regarded as 'normal' hearing.
dB Q is sometimes used to denote weighted noise level, commonly using the ITU-R 468 noise weighting
### Radar
dBZ
### Radio power, energy, and field strength
dBc
dBJ
dBm
dBμ or dBu
dBf
dBW
dBk
## Relative measurements
dBd
dBFS or dBfs
dB-Hz
dBi
dBiC
dBov or dBO
dBr
dBrn
dBc | Decibel
The decibel (dB) is a logarithmic unit of measurement that expresses the magnitude of a physical quantity (usually power or intensity) relative to a specified or implied reference level. Since it expresses a ratio of two (same unit) quantities, it is a dimensionless unit. A decibel is one tenth of a bel (B).
The decibel is useful for a wide variety of measurements in science and engineering (e.g., acoustics and electronics) and other disciplines. It confers a number of advantages, such as the ability to conveniently represent very large or small numbers, a logarithmic scaling that roughly corresponds to the human perception of, for example, sound and light, and the ability to carry out multiplication of ratios by simple addition and subtraction.
The decibel is not an SI unit. However, following the SI convention, the d is lowercase, as it represents the SI prefix deci-, and the B is capitalized, as it is an abbreviation of a name-derived unit (the bel). The full name decibel follows the usual English capitalization rules for a common noun.
The decibel symbol is often qualified with a suffix, which indicates which reference quantity or frequency weighting function has been used. For example, "dBm" indicates that the reference quantity is one milliwatt, while "dBu" is referenced to 0.775 volts. The practice of attaching a suffix in this way, though not permitted by SI,[1] is widely followed.
The definitions of the decibel and bel use base-10 logarithms. For a similar unit using natural logarithms to base e, see neper.
# History
The bel was originally devised by engineers of the Bell Telephone Laboratories to quantify the reduction in audio level over a 1 mile (approximately 1.6 km) length of standard telephone cable. It was originally called the transmission unit or TU, but was renamed in 1923 or 1924 in honor of the Bell System's founder and telecommunications pioneer Alexander Graham Bell. In many situations, however, the bel proved inconveniently large, so the decibel has become more common.
In April 2003, the International Committee for Weights and Measures (CIPM) considered a recommendation for the decibel's inclusion in the SI system, but decided not to adopt the decibel as an SI unit.[2]
# Definitions
## Power
When referring to measurements of power or intensity, a ratio can be expressed in decibels by evaluating ten times the base-10 logarithm of the ratio of the measured quantity to the reference level. Thus, if L represents the ratio of a power value P1 to another power value P0, then LdB represents that ratio expressed in decibels and is calculated using the formula:
L_\mathrm{dB} = 10 \log_{10} \bigg(\frac{P_1}{P_0}\bigg) \,
</math>
Naturally, P1 and P0 must have the same dimension (that is, must measure the same type of quantity), and must as necessary be converted to the same units before calculating the ratio of their numerical values. Note that if P1 = P0 in the above equation, then LdB = 0. If P1 is greater than P0 then LdB is positive; if P1 is less than P0 then LdB is negative.
Rearranging the above equation gives the following formula for P1 in terms of P0 and LdB:
P_1 = 10^\frac{L_\mathrm{dB}}{10} P_0 \,
</math>.
Since a bel is equal to ten decibels, the corresponding formulae for measurement in bels (LB) are
L_\mathrm{B} = \log_{10} \bigg(\frac{P_1}{P_0}\bigg) \,
</math>
P_1 = 10^{L_\mathrm{B}} P_0 \,
</math>.
## Amplitude, voltage and current
When referring to measurements of amplitude it is usual to consider the ratio of the squares of A1 (measured amplitude) and A0 (reference amplitude). This is because in most applications power is proportional to the square of amplitude. Thus the following definition is used:
L_\mathrm{dB} = 10 \log_{10} \bigg(\frac{A_1^2}{A_0^2}\bigg) = 20 \log_{10} \bigg(\frac{A_1}{A_0}\bigg) \,
</math>
The formula may be rearranged to give
A_1 = 10^\frac{L_\mathrm{dB}}{20} A_0 \,
</math>
Similarly, in electrical circuits, dissipated power is typically proportional to the square of voltage or current when the impedance is held constant. Taking voltage as an example, this leads to the equation:
G_\mathrm{dB} =20 \log_{10} \left (\frac{V_1}{V_0} \right ) \quad \mathrm \quad
</math>
where V1 is the voltage being measured, V0 is a specified reference voltage, and GdB is the power gain expressed in decibels. A similar formula holds for current.
## Examples
Note that all of these examples yield dimensionless answers in dB because they are relative ratios expressed in decibels.
- To calculate the ratio of 1 kW (one kilowatt, or 1000 watts) to 1 W in decibels, use the formula
G_\mathrm{dB} = 10 \log_{10} \bigg(\frac{1000 \mathrm{W}}{1 \mathrm{W}}\bigg) = 30 \mathrm{dB} \,
</math>
- To calculate the ratio of 1 mW (one milliwatt) to 10 W in decibels, use the formula
G_\mathrm{dB} = 10 \log_{10} \bigg(\frac{.001 \mathrm{W}}{10 \mathrm{W}}\bigg) = -40 \mathrm{dB} \,
</math>
- To find the power ratio corresponding to a 3 dB change in level, use the formula
G = 10^\frac{3}{10} \times 1\ = 1.99526... \approx 2 \,
</math>
It is seen that there is a 10 dB increase (decrease) for each factor 10 increase (decrease) in the ratio of the two power levels, and approximately a 3 dB increase (decrease) for every factor 2 increase (decrease). In exact terms, the factor is 103/10, or 1.9953, about 0.24% different from exactly 2. Similarly, an increase of 3 dB implies an increase in voltage by a factor of approximately √2, or about 1.41, an increase of 6 dB corresponds to approximately four times the power and twice the voltage, and so on. (In exact terms the power factor is 106/10, or about 3.9811, a relative error of about 0.5%.)
# Merits
The use of the decibel has a number of merits:
- The decibel's logarithmic nature means that a very large range of ratios can be represented by a convenient number, in a similar manner to scientific notation. This allows one to clearly visualize huge changes of some quantity. (See Bode Plot and half logarithm graph.)
- The mathematical properties of logarithms mean that the overall decibel gain of a multi-component system (such as consecutive amplifiers) can be calculated simply by summing the decibel gains of the individual components, rather than needing to multiply amplification factors. Essentially this is because log(A × B × C × ...) = log(A) + log(B) + log(C) + ...
- The human perception of, for example, sound or light, is, roughly speaking, such that a doubling of actual intensity causes perceived intensity to always increase by the same amount, irrespective of the original level. The decibel's logarithmic scale, in which a doubling of power or intensity always causes an increase of approximately 3 dB, corresponds to this perception.
# Uses
## Acoustics
The decibel is commonly used in acoustics to quantify sound levels relative to some 0 dB reference. The reference level is typically set at the threshold of perception of an average human and there are common comparisons used to illustrate different levels of sound pressure.
A reason for using the decibel is that the ear is capable of detecting a very large range of sound pressures. The ratio of the sound pressure that causes permanent damage from short exposure to the limit that (undamaged) ears can hear is above a million. Because the power in a sound wave is proportional to the square of the pressure, the ratio of the maximum power to the minimum power is above one (short scale) trillion. To deal with such a range, logarithmic units are useful: the log of a trillion is 12, so this ratio represents a difference of 120 dB. Since the human ear is not equally sensitive to all the frequencies of sound within the entire spectrum, noise levels at maximum human sensitivity — for example, the higher harmonics of middle A (between 2 and 4 kHz) — are factored more heavily into sound descriptions using a process called frequency weighting.
## Electronics
In electronics, the decibel is often used to express power or amplitude ratios (gains), in preference to arithmetic ratios or percentages. One advantage is that the total decibel gain of a series of components (such as amplifiers and attenuators) can be calculated simply by summing the decibel gains of the individual components. Similarly, in telecommunications, decibels are used to account for the gains and losses of a signal from a transmitter to a receiver through some medium (free space, wave guides, coax, fiber optics, etc.) using a link budget.
The decibel unit can also be combined with a suffix to create an absolute unit of electric power. For example, it can be combined with "m" for "milliwatt" to produce the "dBm". Zero dBm is the power level corresponding to a power of one milliwatt, and 1 dBm is one decibel greater (about 1.259 mW).
In professional audio, a popular unit is the dBu (see below for all the units). The "u" stands for "unloaded", and was probably chosen to be similar to lowercase "v", as dBv was the older name for the same thing. It was changed to avoid confusion with dBV. This unit (dBu) is an RMS measurement of voltage which uses as its reference 0.775 VRMS. Chosen for historical reasons, it is the voltage level which delivers 1 mW of power in a 600 ohm resistor, which used to be the standard reference impedance in almost all professional low-impedance audio circuits.[citation needed]
The bel is used to represent noise power levels in hard drive specifications. It shares the same symbol (B) as the byte.
## Optics
In an optical link, if a known amount of optical power, in dBm (referenced to 1 mW), is launched into a fiber, and the losses, in dB (decibels), of each electronic component (e.g., connectors, splices, and lengths of fiber) are known, the overall link loss may be quickly calculated by addition and subtraction of decibel quantities.
In spectrometry and optics, the blocking unit used to measure optical density is equivalent to −1 B. In astronomy, the apparent magnitude measures the brightness of a star logarithmically, since, just as the ear responds logarithmically to acoustic power, the eye responds logarithmically to brightness; however astronomical magnitudes reverse the sign with respect to the bel, so that the brightest stars have the lowest magnitudes, and the magnitude increases for fainter stars.
# Common reference levels and corresponding units
## "Absolute" and "relative" decibel measurements
Although decibel measurements are always relative to a reference level, if the numerical value of that reference is explicitly and exactly stated, then the decibel measurement is called an "absolute" measurement, in the sense that the exact value of the measured quantity can be recovered using the formula given earlier. For example, since dBm indicates power measurement relative to 1 milliwatt,
- 0 dBm means no change from 1 mW. Thus, 0 dBm is the power level corresponding to a power of exactly 1 mW.
- 3 dBm means 3 dB greater than 0 dBm. Thus, 3 dBm is the power level corresponding to 103/10 × 1 mW, or approximately 2 mW.
- −6 dBm means 6 dB less than 0 dBm. Thus, −6 dBm is the power level corresponding to 10−6/10 × 1 mW, or approximately 250 μW (0.25 mW).
If the numerical value of the reference is not explicitly stated, as in the dB gain of an amplifier, then the decibel measurement is purely relative. The practice of attaching a suffix to the basic dB unit, forming compound units such as dBm, dBu, dBA, etc, is not permitted by SI.[3] However, outside of documents adhering to SI units, the practice is very common as illustrated by the following examples.
## Absolute measurements
### Electric power
dBm or dBmW
dBW
### Voltage
Note that the decibel has a different definition when applied to voltage (as contrasted with power). See the "Definitions" section above.
dBV
dBu or dBv
dBmV
dBμV or dBuV
### Acoustics
dB(SPL)
dB SIL
dB SWL
dB(A), dB(B), and dB(C)
dB HL or dB hearing level is used in Audiograms as a measure of hearing loss. The reference level varies with frequency according to a Minimum audibility curve as defined in ANSI and other standards, such that the resulting audiogram shows deviation from what is regarded as 'normal' hearing.[citation needed]
dB Q is sometimes used to denote weighted noise level, commonly using the ITU-R 468 noise weighting[citation needed]
### Radar
dBZ
### Radio power, energy, and field strength
dBc
dBJ
dBm
dBμ or dBu
dBf
dBW
dBk
## Relative measurements
dBd
dBFS or dBfs
dB-Hz
dBi
dBiC
dBov or dBO
dBr
dBrn
dBc | https://www.wikidoc.org/index.php/Decibel | |
52a1464365b0ccb27a4c94f4fdd0f27f4a1bec5f | wikidoc | Decidua | Decidua
# Overview
Decidua is the term for the uterine lining (endometrium) during a pregnancy, which forms the maternal part of the placenta. It is formed under the influence of progesterone and forms highly-characteristic cells.
# Etymology
The word comes from the Latin deciduus, meaning falling off or shedding.
# Background
After ovulation, in mammals, the endometrial lining becomes transformed into a secretory lining in preparation of accepting the embryo. Without implantation, the secretory lining will be absorbed (estrous cycle) or shed (menstrual cycle).
With implantation the lining now termed decidua evolves further during the pregnancy.
The decidua is shed during the parturition process.
# Structure
Different layers of the deciduas have been described:
- a compact outer layer (stratum compactum)
- an intermediate layer (stratum spongiosum)
- a boundary layer adjacent to the myometrium.
That part of the decidua that interacts with the trophoblast is the decidua vera (“true decidua”). The remainder of the decidua is termed the decidua parietalis.
The decidua has a histologically-distinct appearance, displaying large polygonal decidual cells in the stroma. These are enlarged endometrial stromal cells, which resemble epithelium (and are referred to as "epithelioid").
Formation of a specialized decidua is called decidualization, which is a special property of endometrium seen only in hemochorial placentation.
Decidualization includes the process of differentiation of the spindle-shape stromal fibroblasts into the plump secretory decidual cells, which create a pericellular extracellular matrix rich in fibronectin and laminin (similar to epithelial cells).
Vascularity, as well as vascular permeability, is enhanced in the decidualizing endometrium.
Its leukocyte population is distinct, with the presence of large endometrial granular leukocytes being predominant, while polynuclear leukocytes and B-cells are scant.
The large granular lymphocytes (CD56 bright) are called "uterine NK cells" or "uNK cells" in mice, and "decidual NK cells" or "dNK cells" in humans.
The border to the trophoblast is called Nitabuch’s layer.
# Role
As the maternal interface to the embryo the decidua participates in the exchanges of nutrition, gas, and waste with the gestation. It also protects the pregnancy from the maternal immune system. Further, the decidua has to allow a very controlled invasion of the trophoblast.
In invasive placental disorders like placenta accreta decidualization have been consistently found to be deficient.
# Hormone production
The decidua secretes hormones, growth factors, and cytokines. It has receptors for estrogen, progesterone, growth hormone, and others.
Among its products are hormones commonly associated with other organs such as cortisol, CRF, GnRH, prolactin, and relaxin. Decidual prolactin is not under dopaminergic control.
Pregnancy protein 14 (PP-14), also called placental protein 12, and Insulin-like growth factor-binding protein 1(IGFBP1) appear to be specific products of the secretory and decidual lining.
Other factors released include interleukin-15 and vascular endothelial growth factor (VEGF). A reasonable understanding of the role and interplay of these hormones and factors has not been evolved.
# Other
- In case of an extrauterine pregnancy, the endometrium nevertheless becomes decidualized. A woman may shed the lining in the form of a decidual cast, which may be mistaken as a miscarriage, when, in fact, the ectopic still persists.
- A decidual reaction can be observed in tissue of the peritoneum and ovary during a pregnancy, and represents a response of stromal tissue to progesterone.
# Additional images
- Scheme of placental circulation. | Decidua
Template:Infobox Anatomy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Decidua is the term for the uterine lining (endometrium) during a pregnancy, which forms the maternal part of the placenta. It is formed under the influence of progesterone and forms highly-characteristic cells.
# Etymology
The word comes from the Latin deciduus, meaning falling off or shedding.
# Background
After ovulation, in mammals, the endometrial lining becomes transformed into a secretory lining in preparation of accepting the embryo. Without implantation, the secretory lining will be absorbed (estrous cycle) or shed (menstrual cycle).
With implantation the lining now termed decidua evolves further during the pregnancy.
The decidua is shed during the parturition process.
# Structure
Different layers of the deciduas have been described:
- a compact outer layer (stratum compactum)
- an intermediate layer (stratum spongiosum)
- a boundary layer adjacent to the myometrium.
That part of the decidua that interacts with the trophoblast is the decidua vera (“true decidua”). The remainder of the decidua is termed the decidua parietalis.
The decidua has a histologically-distinct appearance, displaying large polygonal decidual cells in the stroma. These are enlarged endometrial stromal cells, which resemble epithelium (and are referred to as "epithelioid").
Formation of a specialized decidua is called decidualization, which is a special property of endometrium seen only in hemochorial placentation.
Decidualization includes the process of differentiation of the spindle-shape stromal fibroblasts into the plump secretory decidual cells, which create a pericellular extracellular matrix rich in fibronectin and laminin (similar to epithelial cells).
Vascularity, as well as vascular permeability, is enhanced in the decidualizing endometrium.
Its leukocyte population is distinct, with the presence of large endometrial granular leukocytes being predominant, while polynuclear leukocytes and B-cells are scant.
The large granular lymphocytes (CD56 bright) are called "uterine NK cells" or "uNK cells" in mice, and "decidual NK cells" or "dNK cells" in humans.
The border to the trophoblast is called Nitabuch’s layer.
# Role
As the maternal interface to the embryo the decidua participates in the exchanges of nutrition, gas, and waste with the gestation. It also protects the pregnancy from the maternal immune system. Further, the decidua has to allow a very controlled invasion of the trophoblast.
In invasive placental disorders like placenta accreta decidualization have been consistently found to be deficient.
# Hormone production
The decidua secretes hormones, growth factors, and cytokines. It has receptors for estrogen, progesterone, growth hormone, and others.
Among its products are hormones commonly associated with other organs such as cortisol, CRF, GnRH, prolactin, and relaxin. Decidual prolactin is not under dopaminergic control.
Pregnancy protein 14 (PP-14), also called placental protein 12, and Insulin-like growth factor-binding protein 1(IGFBP1) appear to be specific products of the secretory and decidual lining.
Other factors released include interleukin-15 and vascular endothelial growth factor (VEGF). A reasonable understanding of the role and interplay of these hormones and factors has not been evolved.
# Other
- In case of an extrauterine pregnancy, the endometrium nevertheless becomes decidualized. A woman may shed the lining in the form of a decidual cast, which may be mistaken as a miscarriage, when, in fact, the ectopic still persists.
- A decidual reaction can be observed in tissue of the peritoneum and ovary during a pregnancy, and represents a response of stromal tissue to progesterone.
# Additional images
- Scheme of placental circulation. | https://www.wikidoc.org/index.php/Decidua | |
c0d387f1c59048d508870f28df2145251394391c | wikidoc | Decorin | Decorin
Decorin is a protein that in humans is encoded by the DCN gene.
Decorin is a proteoglycan that is on average 90 - 140 kilodaltons (kDa) in molecular weight. It belongs to the small leucine-rich proteoglycan (SLRP) family and consists of a protein core containing leucine repeats with a glycosaminoglycan (GAG) chain consisting of either chondroitin sulfate (CS) or dermatan sulfate (DS).
Decorin is a small cellular or pericellular matrix proteoglycan and is closely related in structure to biglycan protein. Decorin and biglycan are thought to be the result of a gene duplication. This protein is a component of connective tissue, binds to type I collagen fibrils, and plays a role in matrix assembly.
# Naming
Decorin's name is a derivative of both the fact that it "decorates" collagen type I, and that it interacts with the "d" and "e" bands of fibrils of this collagen.
# Function
Decorin appears to influence fibrillogenesis, and also interacts with fibronectin, thrombospondin, the complement component C1q, epidermal growth factor receptor (EGFR) and transforming growth factor-beta (TGF-beta).
Decorin has been shown to either enhance or inhibit the activity of TGF-beta 1. The primary function of decorin involves regulation during the cell cycle.
It has been involved in the regulation of autophagy, of endothelial cell and inhibits angiogenesis. This process is mediated by a high-affinity interaction with VEGFR2 ( vascular endothelial growth factor receptor) which leads to increased levels of tumor suppressor gene called PEG3. Other angiogenic growth factors that decorin inhibits are angiopoietin, hepatocyte growth factor (HGF) and platelet-derived growth factor (PDGF).
Decorin has recently been established as a myokine. In this role, it promotes muscle hypertrophy by binding with myostatin.
# Clinical signifiance
Keloid scars have decreased decorin expression compared to healthy skin.
# Animal studies
Infusion of decorin into experimental rodent spinal cord injuries has been shown to suppress scar formation and promote axon growth.
Decorin has been shown to have anti-tumorigenic properties in an experimental murine tumor model and is capable of suppressing the growth of various tumor cell lines. There are multiple alternatively spliced transcript variants known for the decorin gene. Mutations in the decorin gene are associated with congenital stromal corneal dystrophy.
# Interactions
Decorin has been shown to interact with:
- Collagen type I
- Epidermal growth factor receptor and
- TGF beta 1,
- TLR2, and
- TLR4. | Decorin
Decorin is a protein that in humans is encoded by the DCN gene.
Decorin is a proteoglycan that is on average 90 - 140 kilodaltons (kDa) in molecular weight. It belongs to the small leucine-rich proteoglycan (SLRP) family and consists of a protein core containing leucine repeats with a glycosaminoglycan (GAG) chain consisting of either chondroitin sulfate (CS) or dermatan sulfate (DS).
Decorin is a small cellular or pericellular matrix proteoglycan and is closely related in structure to biglycan protein. Decorin and biglycan are thought to be the result of a gene duplication. This protein is a component of connective tissue, binds to type I collagen fibrils, and plays a role in matrix assembly.[1]
# Naming
Decorin's name is a derivative of both the fact that it "decorates" collagen type I, and that it interacts with the "d" and "e" bands of fibrils of this collagen.
# Function
Decorin appears to influence fibrillogenesis, and also interacts with fibronectin, thrombospondin, the complement component C1q, epidermal growth factor receptor (EGFR) and transforming growth factor-beta (TGF-beta).
Decorin has been shown to either enhance or inhibit the activity of TGF-beta 1. The primary function of decorin involves regulation during the cell cycle.
It has been involved in the regulation of autophagy, of endothelial cell and inhibits angiogenesis. This process is mediated by a high-affinity interaction with VEGFR2 ( vascular endothelial growth factor receptor) which leads to increased levels of tumor suppressor gene called PEG3.[2] Other angiogenic growth factors that decorin inhibits are angiopoietin, hepatocyte growth factor (HGF) and platelet-derived growth factor (PDGF).[3]
Decorin has recently been established as a myokine. In this role, it promotes muscle hypertrophy by binding with myostatin.[4]
# Clinical signifiance
Keloid scars have decreased decorin expression compared to healthy skin.[5]
# Animal studies
Infusion of decorin into experimental rodent spinal cord injuries has been shown to suppress scar formation and promote axon growth.
Decorin has been shown to have anti-tumorigenic properties in an experimental murine tumor model and is capable of suppressing the growth of various tumor cell lines. There are multiple alternatively spliced transcript variants known for the decorin gene. Mutations in the decorin gene are associated with congenital stromal corneal dystrophy.[1]
# Interactions
Decorin has been shown to interact with:
- Collagen type I[6]
- Epidermal growth factor receptor[7][8] and
- TGF beta 1,[6][9][10]
- TLR2,[11] and
- TLR4.[11] | https://www.wikidoc.org/index.php/Decorin | |
866eaaad25cc74585095f4f262fcd6a6ccf49f5b | wikidoc | Massage | Massage
Massage is the treatment and practice of manipulation of the soft body tissues with physical, functional, i.e. mechanical, medical/therapeutic, and in some cases psychological purposes and goals. The word comes from the French massage "friction of kneading," possibly from Arabic massa "to touch, feel, handle" or from Latin massa "mass, dough". (In distinction the ancient Greek word for massage itself was anatripsis , and the Latin was frictio.)
Massage involves acting and manipulating the patient's body with pressure (structured, unstructured, stationary, and/or moving), tension, motion, or vibration done manually or with mechanical aids. Target tissues may include muscles, tendons, ligaments, skin, joints, or other connective tissue, as well as lymphatic vessels, and/or organs of the gastrointestinal system. Massage can be applied with the hands, fingers, elbows, forearm, and feet. There are over eighty different massage modalities. The most cited reasons for introducing massage was patient demand and perceived clinical effectiveness.
In professional settings, massage involves the client being treated while lying on a massage table, sitting upright in a massage chair, or lying on a pad on the floor. Except for modalities such as Acupressure, Shiatsu, Tui Na, Thai Massage, or Barefoot Deep Tissue, the massage subject is generally unclothed or partially unclothed, also referred to as disrobed, and their body would be "draped" with towels or sheets.
# History
## Ancient and medieval times
Writings on massage have been found in many ancient civilizations such as Rome, Greece, Japan, China, Egypt, and India. Hippocrates wrote in 460 BC that "The physician must be experienced in many things, but assuredly in rubbing."
The ancient Chinese book called Huangdi Neijing by the Yellow Emperor recommended "massage of skin and flesh."
The technique of massage abortion, involving the application of pressure to the pregnant abdomen, has been practiced in Southeast Asia for centuries. One of the bas reliefs decorating the temple of Angkor Wat in Cambodia, dated circa 1150, depicts a demon performing such an abortion upon a woman who has been sent to the underworld. This is believed to be the oldest known visual representation of abortion.
In Romania some illnesses were treated by a massage in which the patient was treaded on by a tame bear..
## Modern times
United States:
Massage started to become popular in the United States in the middle part of the 1800s and was introduced by two New York physicians based on Per Henrik Ling's techniques developed in Sweden.
During the 1930s and 1940s massage's influence decreased because of recent medical advancement, while in the 1970s massage's influence grew once again with a notable rise among athletes. Massage was used up until the 1960s and 1970s by nurses to help ease patients’ pain and help them sleep.
Because it is illegal to advertise or offer sexual services in most of the United States, such services are sometimes advertised as "massage".
United Kingdom:
Massage is popular in the United Kingdom today and gaining. There are many private practitioners working from there own premises as well as those who operate from commercial venues.
Massage in sports, business and organizations:
The 1996 Summer Olympics in Atlanta was the first time that massage was offered as a core medical service. Massage has been employed by businesses and organizations such as the U.S. Department of Justice, Boeing and Reebok.
# Equipment
### Massage Table
A typical commercial massage table has an easily cleaned, heavily padded surface, and a horseshoe-shaped head support that allows the client to breathe easily while lying face down and can be stationary or portable. An orthopedic pillow or bolster can be used to correct body positioning.
### Massage Chair
Ergonomically designed massage chairs for positioning a person who will be receiving a massage, similar in function to a massage table. Chairs may be either stationary or portable models.
Massage chairs are easier for the practitioner to maneuver than massage tables, and clients do not need to disrobe to receive a chair massage. Due to these two factors, chair massage is often performed in settings such as corporate offices, outdoor festivals, shopping malls, and other public locations.
### Oil
Many different types of oils can be used including fractionated coconut oil, grape seed oil, macadamia oil, sesame oil, pecan oil, and mustard oil. Arnica, from the flowers or leaves of the Arnica montana. Often uses olive oil as a base when used medicinally, or almond oil when used as a massage oil.
Aromatherapy oils such as neroli oil and pine oil can also be mixed with carrier oils.
### Mechanical aids
Electronic massage chairs are commercially available, which operate without any manual help. Lexus cars of the fourth generation LS include shiatsu and shoulder massage systems.
# Massage methods
Massage can be performed by a professional Massage Practitioner, or by other health care professionals, such as chiropractors, osteopath, Athletic trainers, and/or physical therapists. Massage therapists work in hospitals as allied health professioners, in nursing homes, sports and fitness facilities, spas, beauty salons, cruise ships, private offices, and travel to private residences or businesses. Contraindications to massage include, deep vein thrombosis, bleeding disorders or taking blood thinners such as Warfarin, damaged blood vessels, weakened bones from cancer, osteoporosis, or fractures, and fever.
## Acupressure
## Ayurvedic Abhyanga massage
Ayurveda is a natural health care system originating in India over 5,000 years ago. It incorporates massage, yoga, meditation and herbal remedies. Ayurvedic Massage, also known as Abhyanga part of Panchakarma is usually performed by one or two therapists using a heated blend of herbal oils that are believed to be based on the body's dosha.The aim is to loosen the excess doshas through techniques such as kneading, rubbing, and squeezing. The feet are used in chavutti thirummal, a specialized technique where the therapist suspends himself by a rope from the ceiling to apply extra pressure with his feet.
## Barefoot deep tissue
Barefoot deep tissue is a blend of Eastern barefoot techniques with Western manual therapy. Clients typically wear loose clothes while lying on a mat on the floor in supine, prone and side-lying positions with pillows or bolsters with no oil used. Because the therapist can apply a broad range of pressure with ease and does not have to strain, more effort and concentration can be used to sense and manipulate tissue, release fascia, as well as search for and attack trigger points, regardless of client's size or build.
John Harris, who worked in the 1984 Olympics developed this modality.
## Bowen therapy
Bowen technique involves a rolling type movement over fascia, muscles, ligaments, tendons and joints. It is said not to involve deep or prolonged contact with muscle tissues as in most kinds of massage, but claims to relieve muscle tensions and strains and to restore normal lymphatic flow. It is based on practices developed by Australian Tom Bowen.
## Breema
Breema bodywork is performed on the floor with the recipient fully clothed. It consists of rhythmical and gentle leans and stretches. Fifty minute sessions are common. There are also self-Breema exercises. The essence of Breema is expressed in the Nine Principles of Harmony.
## Chair massage
"Seated massage" (also refereed to as chair-massage), is done in a variety of diverse settings, e.g., business,corporate and clinical settings, and in public areas such as airports, shopping centers, sport clubs, and salons. A seated-massage typically lasts 10-30 minutes, and is performed while fully clothed. Seated massage is an excellent technique to use for working on the neck, shoulders and upper back areas of the body. Due to the way the individual is positioned, seated massage allows the therapist to work with the force of gravity while doing a treatment.
## Champissage
Champissage or (Indian head massage) has been used in India for centuries. It combines massage with the more subtle form of chakra balancing. It is normally done by applying oil over the body. Also called 'champi' or Maalis. The word shampoo in English usage dates back to 1762, with the meaning "to massage". The word was a loan from Anglo-Indian shampoo, in turn from Hindi chāmpo (चाँपो Template:IPA), imperative of chāmpnā (चाँपना Template:IPA), "to smear, knead the muscles, massage". It itself comes from Sanskrit/Hindi word "champā" (चम्पा Template:IPA), the flowers of the plant Michelia champaca which have traditionally been used to make fragrant hair-oil. It is often performed by the barber after a haircut on the head, shoulders, arms, and neck.
The term and service was introduced by a Bengali entrepreneur Sake Dean Mahomed, who opened a shampooing bath known as 'Mahomed's Indian Vapour Baths' in Brighton, England in 1759.
## Craniosacral therapy
Craniosacral therapy is a gentle, hands-on method of evaluating the functioning of the craniosacral system, and is often mistakenly referred to as a type of massage. It works through using the body's own self-correcting mechanisms rather than the application of physical force from the practitioner. When used by a massage practitioner, craniosacral therapy can usefully complement the massage treatment,
## Deep tissue massage
Deep tissue techniques are generally designed for more focused massage work. Working a specific joint, muscle or muscle group, the practitioner can access deeper layers of the soft tissue. Starting superficially and easing into the depth of the muscle slowly often allows more movement. If the pressure is applied too deeply or too quickly, the muscle may tighten to protect that area, and unnecessary damage or inflammation can be induced. Very little lubricant is used as the pressure doesn't travel much over the skin.
The most commonly used 'tools' during deep tissue massage may include, 3 and 6 fingers, reinforced fingers, knuckles, a flat elbow, opposing thumbs, the heel of the hand or foot, and the forearm. Deep tissue is similar to Myofascial Release.
Deep muscle therapy was created by Therese Pfrimmer of Canada.
## Horstmann technique
Practical technique that works by initially balancing the "energy field" and then holding on special energy points while mobilising limbs.
## Esalen Massage
Esalen Massage was developed by Charlotte Selver and works with gentle rocking of the body, passive joint exercises and deep structural work on the muscles and joints, together with an energetic balancing of the body.
## Infant massage
Shantala massage is an ancient Indian massage technique with a rhythmic character, given to massage babies and children. It was introduced into Western society by Dr. Frederique Leboyer, a French obstetrician.
## Lomilomi
Lomilomi is the traditional massage of Hawaii. As an indigenous practice, it varies by island and by family. The styles most known today are those of Auntie Margaret Machado of the island of Hawaii, Uncle Kalua Kaiahua of Maui and Oahu, and Kahu Abraham Kawaii of Kaua'i, who called his style Kahuna Bodywork. Other names given to massage performed in Hawaii are temple style, lomi lomi, lomi lomi nui, romi kapa rere, romi romi and ma-uri. Some of these styles may be traditional, and others may have been influenced by or created in modern times. The purported Lomilomi massage given by Barbra Streisand to Robert De Niro in "Meet the Fockers" was not an accurate representation of the style.
## Medical massage
Massage used in the medical field includes Manual lymphatic drainage used for lymphedema which can be used in conjunction with the treatment of breast cancer. Carotid sinus massage is used to diagnose carotid sinus syncope and is sometimes useful for differentiating supraventricular tachycardia (SVT) from ventricular tachycardia. It, like the valsalva maneuver, is a therapy for SVT. However, it is less effective than pharmaceutical management of SVT with verapamil or adenosine.
## Myofascial release
Myofascial release refers to the manual massage technique for stretching the fascia and releasing bonds between fascia, integument, and muscles with the goal of eliminating pain, increasing range of motion and equilibrioception. Injuries, stress, trauma, overuse and poor posture can cause restriction to fascia. This is usually done by applying shear compression or tension in various directions, or by skin rolling. Myofascial release originators come from Physical Therapy and from Structural Integration (Rolfing); its current developers include John Barnes, Art Riggs, Michael Stanborough, Tom Myers, Til Luchau and Michael Leahy, the originator of a complete regime called Active Release Technique or ART.
Proprioceptive Neuromuscular Facilitation (PNF) and myofacial techniques are believed to lengthen tight/facilitated muscles while fiber activation techniques are believed tone weak/inhibited muscles.
## Neuromuscular therapy
Neuromuscular Therapy (NMT) is used for pain relief. Perceived imbalances in Human position are assessed initially through a postural assessment. These are then addressed through systematic and site specific massage. NMT was developed in the 1930s by Dr. Stanley Leif, current practitioners include Paul St. John.
## Nihon Kaifuku Anma - Traditional Japanese massage
Introduced to Japan about 1300 years ago. Anma is deep tissue work using no oils and is based on kneading movements. Shiatsu massage grew out of this rich tradition.
## Pregnancy massage
Doulas will often use massage in an attempt to smooth the labor process.
## Reflexology massage
Reflexology, also called Foot zone therapy, is traditionally practiced without lotion, as the pressure points on the feet are stimulated by thumb and finger walking, as well as static pressure. Foot massage practitioners believe that the ailment of an internal organ will be associated with the nerve ending on the sole of the foot. As pressure is applied to the sole, theory holds that a healthy patient should not feel any strong pain. This theory is based on a perceived energetic flow of "meridians" in the body, also known as Chi.
Before the massage, the patient's feet are soaked for about ten minutes in a foot bath, typically a solution of hot water and Chinese herbs. The practitioner rubs and massages the painful spots to break down rough spots and accumulated crystals which have not been scientifically researched. Based on this idea, some shoe liners are made with pressure points to stimulate the soles of the feet.
## Shiatsu
Shiatsu (指圧) is a form of Japanese massage that uses thumb pressure and works along the same energy meridians as acupressure and incorporates stretching. While receiving Shiatsu, you are fully clothed while laying on a mat on the floor.
## Soft tissue therapy
Treatment techniques include trigger point therapy, myofascial Release, friction for adhesions between fascial layers and muscles. Sustained finger pressure to alleviate hypertonic, or tight, areas within muscle and fascia, active Release therapies, and deep tissue massage are all derivatives of soft tissue therapy. Different types of stretching such as static stretching, dynamic stretching, and/or PNF stretching (proprioceptive neuromuscular facilitation).
Another form of Soft tissue therapy is Muscle energy technique (MET) which uses reciprocal inhibition (RI) which is when the therapist uses a client’s muscle to stretch the opposing muscle. The therapist takes the muscle that they are wishing to stretch to its full range of motion. The therapist then gets the client to use the opposing muscle by moving away from the therapist. When the client relaxes the therapist then moves the muscle in an attempt to realign the muscle fibers.
## Sports massage
A Sports Massage can be described as massage that has derived from the Swedish style massage specifically to treat sporting injuries and sports persons, pre and post-event. The same techniques of effleurage, petrissage, friction, tapotement, compression, and vibration are employed; however, the movements are often reinforced, which makes the effect much deeper, and are usually targeted towards specific muscles and tissues to treat them in isolation, as well as holistically.
A Sports Massage may involve treating the entire body, as part of a training routine, or more usually a specific area is treated due to a particular muscle strain or injury.
Due to the nature of various sports and athletic pursuits, clients may attend for treatment with recent injuries. Direct pressure over the injury site is specifically contra-indicated for 48-72 hours after the occurrence; this over and above the standard massage contra-indications.
Neuro Muscular Technique (NMT) and Muscle Energy Technique (MET) are often used by the Sports Massage Therapist to treat high degrees of tension or 'knotting' of specific muscles. These techniques are extremely useful in relaxing the muscles sufficiently to allow the therapist perform a more standard massage routine.
## Stone massage
Heated stones were used by Egyptians, Native Americans and in Lomilomi massage. Smooth hot or cold stones, usually basalt or marble, are used to massage the body. When heated stones are used, muscles relax, allowing the massage therapist to work deeper into the muscle. Energy medicine is sometimes incorporated into stone massage. Stones are heated in hot water and are placed under the back, along both sides of the spine, and on top of the torso and are believed to heat the chakra or meridians centers. Heated stones coated in oil are then used directly in the hands of the therapist delivering various massaging strokes.
## Structural Integration
Rolfing, a method of Structural Integration, works with realigning the body structurally and human gait.
## Swedish massage
This style utilizes long, flowing strokes, often but not necessarily in the direction of the heart. There are six basic strokes: effleurage from the French effleurer, 'to skim over', petrissage from the French pétrir, 'to knead', friction, tapotement, compression, and vibration. Petrissage is a kneading movement with the whole palm or finger tips, using wringing, skin rolling, compression, and/or lifting. Petrissage is usually applied vertically to the muscle tissue. Oil, cream, or lotion is applied on the skin to reduce friction and allow smooth strokes. Effleurage consists of long, flowing or gliding strokes, performed with open hands. In many massage sessions, effleurage is used as the initial type of stroking, as it has a calming effect when performed slowly. Swedish massage has shown to be helpful in reducing pain, joint stiffness, and improving function in patients with osteoarthritis of the knee over a period of eight weeks.
### History
This style of massage is generally attributed to the Swedish fencing master and gymnastics teacher Per Henrik Ling (1776-1839). However, it was in fact the Dutch practitioner Johan Georg Mezger (1838-1909) who adopted the French names to denote the basic strokes. The term Swedish Movement System was transposed to Swedish Massage System sometime during the second half of the 19th century. Ling’s system was the Swedish Movement System or Swedish Gymnastic Movement System. This may be how he has become incorrectly associated for so long with Swedish massage.
## Tai Ji/Tai Chi massage
This massage uses the natural principles of Yin and Yang to achieve balance in the energies of the body. Practitioners of Tai Ji believe that it uses Tao and deals with Qi blockages.
## Thai massage
Known in Thailand as นวดแผนโบราณ (Nuat phaen boran, IPA Template:IPA), meaning "ancient/traditional massage", Thai massage is also known as Thai ancient massage, traditional Thai massage, Thai yoga massage, yoga massage, Thai classical massage, Thai bodywork, passive yoga or assisted yoga. Thai massage originated in India based and is based on Ayurveda and yoga, thereafter becoming popular in ancient Siam, now known as Thailand. It was believed that the massage art was brought over to Thailand by Shivago Komarpaj (Jivaka Kumarabhacca), a contemporary of Gautama Buddha over 2500 years ago.
The receiver is put into many yoga like positions during the course of the massage. In the northern style based out of Chiang Mai, Thailand there is a lot of stretching movements, unlike the southern style where acupressure is emphasized.
The massage recipient changes into loose, comfortable clothes and lies on a mat or firm mattress on the floor. (It can be done solo or in a group of a dozen or so patients in the same large room.) The massage practitioner leans on the recipient's body using hands and usually straight forearms locked at the elbow to apply firm rhythmic pressure. The massage generally follows the Sen lines on the body — somewhat analogous to meridians or Channel (Chinese medicine) and Indian nadis. Legs and feet of the giver can be used to fixate the body or limbs of the recipient. In other styles, hands fixate the body, while the feet do the massaging action. Oil is not used in traditional Thai Massage. A full Thai massage session typically lasts two hours or more, and includes rhythmic pressing and stretching of the entire body; this may include pulling fingers, toes, ears, cracking the knuckles, walking on the recipient's back, and arching the recipient's into bhujangasana or (cobra position). There is a standard procedure and rhythm to this massage. In Thailand a two hour massage might cost around 300 Thai baht (US $8 in 2005) depending on location (it may cost ten times more inside a five star hotel).
Note: The traditional therapeutic practice of Thai massage should not be confused with the sexual service of the same name that is available in some hotels and brothels. Sometimes the traditional therapeutic Thai Massage, or ancient massage, is referred to as "old lady massage", while the sexual practice, which has nothing to do with therapeutic traditional massage is called "young lady massage".
## Traditional Chinese massage
Tui Na (推拿) focusing on pushing, stretching and kneading the muscle. Zhi Ya (指壓) is similar to Tui Na massage except it focuses more on pinching and pressing at acupressure points. They are both based on principles from Traditional Chinese Medicine.
## Trager Approach
The Trager Approach combines movement, massage and education.
## Trigger point therapy
This can also be called pressure point massage. A trigger point is an area of a muscle (about 50 cells) that may refer pain sensations to other parts of the body. Manual pressure is applied to these points. This work was founded by Dr. Janet G. Travell, U.S. President John F. Kennedy's physician and David Simons. This work can be incorporated into other styles of massage therapy such as neuromuscular therapy (NMT) or Swedish.
## Visceral manipulation
One form is Mayan abdominal massage which is practiced in many countries in Latin America. This type of massage was developed by Don Elijio Panti and Dr. Rosita Arvigo of Peru.
Mantak Chia introduced a form of abdomen massage called Chi Nei Tsang, which he teaches, helps to "clears negative emotions" (in the form of "bad winds" or "sick winds") which gather near the navel.
## Watsu
Watsu is the combination of hydrotherapy and Shiatsu developed by Harold Dull in his time spent at Harbin Hot Springs near Middletown, California, USA. The work is done in skin temperature water with both the therapist and practitioner in the water, usually a pool which is between 3.5 ft to 4 ft. (100–120 cm) deep. The work entails much movement in the water and practitioners believe that it incorporates the activation of the energy lines derived from Shiatsu.
# Associated methods
Many types of practices are associated with massage and include Bodywork (alternative medicine), manual therapy, energy medicine, and breathwork. Other names for massage and related practices include hands-on work, body/somatic therapy, and somatic movement education. Body-mind integration techniques stress self-awareness and movement over physical manipulations by a practitioner. Therapies related to movement awareness/education are closer to Dance and movement therapies. Massage can also have connections with the New Age movement and alternative medicine as well as being used by mainstream medical practitioners.
# Beneficial effects
Peer-reviewed medical research has shown that the benefits of massage include pain relief, reduced trait anxiety and depression, and temporarily reduced blood pressure, heart rate, and state anxiety. Theories behind what massage might do include blocking nociception (gate control theory), activating the parasympathetic nervous system which may stimulate the release of endorphins and serotonin, preventing fibrosis or scar tissue, increasing the flow of lymph, and improving sleep but such effects are yet to be supported by well designed clinical studies.
Massage is hindered from reaching the gold standard of scientific research which includes placebo-controlled and double blind clinical trials. Developing a "sham" manual therapy for massage would be difficult since even light touch massage could not be assumed to be completely devoid of effects on the subject. It would also be difficult to find a subject that would not notice that they were getting less of a massage and it would be impossible to blind the therapist. Massage can employ randomized controlled trials which are published in peer reviewed medical journals. This type of study could increase the credibility of the profession because it displays that purported therapeutic effects are reproducible.
## Single dose effects
Pain relief:
Relief from pain due to musculoskeletal injuries and other causes is cited as a major benefit of massage. In one study, cancer patients self-reported symptomatic relief of pain. This study, however, did not include a no treatment or placebo control group so these effect may be due to the placebo effect or regression towards the mean. Massage can also relieve tension headaches. Acupressure or pressure point massage may be more beneficial than classic Swedish massage in relieving back pain. However, a meta-study conducted by scientists at the University of Illinois at Urbana-Champaign failed to find a statistically significant reduction in pain immediately following treatment.
State anxiety:
Massage has been shown to reduce state anxiety, a transient measure of anxiety in a given situation.
Blood pressure and heart rate:
Massage has been shown to reduce blood pressure and heart rate as temporary effects.
Attention:
After massage, EEG patterns indicate enhanced performance and alertness on mathematical computations, with the effects perhaps being mediated by decreased stress hormones.
Other:
Massage also stimulates the immune system by increasing peripheral blood lymphocytes (PBLs). However, this immune system effect is only observed in aromatherapy massage, which includes sweet almond oil, lavender oil, cypress oil, and sweet marjoram oil. It is unclear whether this effect persists over the long term.
## Multiple dose effects
Pain relief:
When combined with education and exercises, massage might help sub-acute, chronic, non-specific low back pain. Furthermore, massage has been shown to reduce pain experienced in the days or weeks after treatment.
Trait anxiety:
Massage has been shown to reduce trait anxiety; a person's general susceptibility to anxiety.
Depression:
Massage has been shown to reduce subclinical depression.
Diseases:
Massage, involving stretching, has been shown to help with spastic diplegia resulting from Cerebral palsy in a small pilot study. The researchers warn that these results should "be viewed with caution until a double-blind controlled trial can be conducted".
Massage has been used in an effort to improve symptoms, disease progression, and quality of life in HIV patients, however, this treatment is not scientifically supported.
# Regulation
In the USA there are about 90,000 massage therapists. Training programs in the US are typically 500–1000 hours in length, and can award a certificate, diploma, or degree depending on the particular school. There are around 1,300 programs training massage therapists in the country and study will often include anatomy and physiology, kinesiology, massage techniques, first aid and CPR, business, ethical and legal issues, and hands on practice along with continuing education requirements if regulated. The Commission on Massage Therapy Accreditation (COMTA) is one of the organizations that works with massage schools in the U.S..
38 states and the District of Columbia require some type of licencing for massage therapists.
In the US, 32 states use the National Certification Board for Therapeutic Massage and Bodywork's certification program as a basis for granting licenses either by rule or statute. The National Board grants the designation Nationally Certified in Therapeutic Massage and Bodywork (NCTMB). There are two tests available and you can become certified through a porfolio process if you have equivalent training and experience. Between 10-20% of towns or counties regulate the profession. These local regulations can range from prohibition on opposite sex massage, fingerprinting and venereal checks from a doctor, to prohibition on house calls because of concern reguarding sale of sexual services.
In the USA licensure is the highest level of regulation and this restricts anyone without a license from practicing massage therapy or by calling themselves that protected title. Certification allows only those who meet certain educational criteria to use the protected title and registration only requires a listing of therapists who apply and meet an educational requirement.
In Canada only three provinces regulate massage therapy they are British Columbia, Ontario, and Newfoundland and Labrador. The Canadian Massage Therapists Alliance (CMTA) has set a level of 2200 practice hours in Ontario, and Newfoundland and Labrador and 3000 hours in British Columbia.
In India, massage therapy is licenced by The Department of Ayurveda, Yoga & Naturopathy, Unani, Siddha and Homoeopathy (AYUSH) under the Ministry of Health and Family Welfare (India) in March of 1995.
Because the art and science of massage is a globally diverse phenomenon, different legal jurisdictions sometimes recognize and license individuals with titles. Examples are:
- Registered Massage Therapist (RMT) Canada
- Certified Massage Therapist (CMT)
- Licensed Massage Practitioner (LMP)
- Licensed Massage Therapist (LMT)
- Licensed Massage and Bodywork Therapist (LMBT) North Carolina
# Prevalence in the United States
In 1997 there was an estimated 114 million visits to massage therapists in the US. Massage therapy is the most used type of Complementary and alternative medicine in hospitals in the United States.
People state that they use massage because they believe that it relieves pain from musculoskeletal injuries and other causes of pain, reduces stress and enhances relaxation, rehabilitates sports injuries, decreases feelings of anxiety and depression, and increases general well being.
In a poll of 25-35 year olds 79% said they would like their health insurance plan to cover massage. Some of the companies that offer massage to their employees include Allstate, Best Buy, Cisco Systems, FedEx, Gannett (which runs USA Today), General Electric, Hewlett-Packard, Home Depot, JC Penney, Kimberly-Clark, Texas Instruments and Yahoo. In 2006 Duke University Health System opened up a center to integrate medical disciplines with CAM disciplines such as massage therapy and acupuncture, this trend was started by Andrew Weil. There were 15,500 spas in the United States in 2007 with about a third of the visitors being men.
The number of visits rose from 91 million in 1999 to 136 million in 2003, generating a revenue that equals $11 billion.
# Prevalence in Asia
In Asia, bathroom attendants may provide a hot face towel and a massage.
# Notable practitioners
Heinrich Himmler, commander of the Schutzstaffel (SS) and one of the most powerful men in Nazi Germany might have lost faith in German victory due to his discussions with his masseurs Felix Kersten and Walter Schellenberg.
Albert Bedane (1893–1980) who provided shelter to a Jewish woman and others during World War II was a massage/physiotherapist. | Massage
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Massage is the treatment and practice of manipulation of the soft body tissues with physical, functional, i.e. mechanical, medical/therapeutic, and in some cases psychological purposes and goals.[1] The word comes from the French massage "friction of kneading," possibly from Arabic massa "to touch, feel, handle" or from Latin massa "mass, dough". [2][3] (In distinction the ancient Greek word for massage itself was anatripsis [4], and the Latin was frictio.)
Massage involves acting and manipulating the patient's body with pressure (structured, unstructured, stationary, and/or moving), tension, motion, or vibration done manually or with mechanical aids. Target tissues may include muscles, tendons, ligaments, skin, joints, or other connective tissue, as well as lymphatic vessels, and/or organs of the gastrointestinal system. Massage can be applied with the hands, fingers, elbows, forearm, and feet. There are over eighty different massage modalities. [5] The most cited reasons for introducing massage was patient demand and perceived clinical effectiveness.[6]
In professional settings, massage involves the client being treated while lying on a massage table, sitting upright in a massage chair, or lying on a pad on the floor. Except for modalities such as Acupressure, Shiatsu, Tui Na, Thai Massage, or Barefoot Deep Tissue, the massage subject is generally unclothed or partially unclothed, also referred to as disrobed, and their body would be "draped" with towels or sheets.
Template:TOClimit
# History
## Ancient and medieval times
Writings on massage have been found in many ancient civilizations such as Rome, Greece, Japan, China, Egypt, and India. [5]Hippocrates wrote in 460 BC that "The physician must be experienced in many things, but assuredly in rubbing." [7]
The ancient Chinese book called Huangdi Neijing by the Yellow Emperor recommended "massage of skin and flesh."[8]
The technique of massage abortion, involving the application of pressure to the pregnant abdomen, has been practiced in Southeast Asia for centuries. One of the bas reliefs decorating the temple of Angkor Wat in Cambodia, dated circa 1150, depicts a demon performing such an abortion upon a woman who has been sent to the underworld. This is believed to be the oldest known visual representation of abortion.[9]
In Romania some illnesses were treated by a massage in which the patient was treaded on by a tame bear.[10].
## Modern times
United States:
Massage started to become popular in the United States in the middle part of the 1800s [5] and was introduced by two New York physicians based on Per Henrik Ling's techniques developed in Sweden. [7]
During the 1930s and 1940s massage's influence decreased because of recent medical advancement, while in the 1970s massage's influence grew once again with a notable rise among athletes. [5] Massage was used up until the 1960s and 1970s by nurses to help ease patients’ pain and help them sleep.[11]
Because it is illegal to advertise or offer sexual services in most of the United States, such services are sometimes advertised as "massage".
United Kingdom:
Massage is popular in the United Kingdom today and gaining. There are many private practitioners working from there own premises as well as those who operate from commercial venues.
Massage in sports, business and organizations:
The 1996 Summer Olympics in Atlanta was the first time that massage was offered as a core medical service. [8] Massage has been employed by businesses and organizations such as the U.S. Department of Justice, Boeing and Reebok.[12]
# Equipment
### Massage Table
A typical commercial massage table has an easily cleaned, heavily padded surface, and a horseshoe-shaped head support that allows the client to breathe easily while lying face down and can be stationary or portable. An orthopedic pillow or bolster can be used to correct body positioning.
### Massage Chair
Ergonomically designed massage chairs for positioning a person who will be receiving a massage, similar in function to a massage table. Chairs may be either stationary or portable models.
Massage chairs are easier for the practitioner to maneuver than massage tables, and clients do not need to disrobe to receive a chair massage. Due to these two factors, chair massage is often performed in settings such as corporate offices, outdoor festivals, shopping malls, and other public locations.
### Oil
Many different types of oils can be used including fractionated coconut oil, grape seed oil, macadamia oil, sesame oil, pecan oil, and mustard oil. Arnica, from the flowers or leaves of the Arnica montana. Often uses olive oil as a base when used medicinally, or almond oil when used as a massage oil.[13]
Aromatherapy oils such as neroli oil and pine oil can also be mixed with carrier oils.
### Mechanical aids
Electronic massage chairs are commercially available, which operate without any manual help. Lexus cars of the fourth generation LS include shiatsu and shoulder massage systems. [14]
# Massage methods
Massage can be performed by a professional Massage Practitioner, or by other health care professionals, such as chiropractors, osteopath, Athletic trainers, and/or physical therapists. Massage therapists work in hospitals as allied health professioners, in nursing homes, sports and fitness facilities, spas, beauty salons, cruise ships, private offices, and travel to private residences or businesses. [5] Contraindications to massage include, deep vein thrombosis, bleeding disorders or taking blood thinners such as Warfarin, damaged blood vessels, weakened bones from cancer, osteoporosis, or fractures, and fever. [5]
## Acupressure
## Ayurvedic Abhyanga massage
Ayurveda is a natural health care system originating in India over 5,000 years ago. It incorporates massage, yoga, meditation and herbal remedies. Ayurvedic Massage, also known as Abhyanga part of Panchakarma is usually performed by one or two therapists using a heated blend of herbal oils that are believed to be based on the body's dosha.The aim is to loosen the excess doshas through techniques such as kneading, rubbing, and squeezing. The feet are used in chavutti thirummal, a specialized technique where the therapist suspends himself by a rope from the ceiling to apply extra pressure with his feet.
## Barefoot deep tissue
Barefoot deep tissue is a blend of Eastern barefoot techniques with Western manual therapy. Clients typically wear loose clothes while lying on a mat on the floor in supine, prone and side-lying positions with pillows or bolsters with no oil used. Because the therapist can apply a broad range of pressure with ease and does not have to strain, more effort and concentration can be used to sense and manipulate tissue, release fascia, as well as search for and attack trigger points, regardless of client's size or build.
John Harris, who worked in the 1984 Olympics developed this modality.
## Bowen therapy
Bowen technique involves a rolling type movement over fascia, muscles, ligaments, tendons and joints. It is said not to involve deep or prolonged contact with muscle tissues as in most kinds of massage, but claims to relieve muscle tensions and strains and to restore normal lymphatic flow. It is based on practices developed by Australian Tom Bowen.[15]
## Breema
Breema bodywork is performed on the floor with the recipient fully clothed. It consists of rhythmical and gentle leans and stretches. Fifty minute sessions are common. There are also self-Breema exercises. The essence of Breema is expressed in the Nine Principles of Harmony.
## Chair massage
"Seated massage" (also refereed to as chair-massage), is done in a variety of diverse settings, e.g., business,corporate and clinical settings, and in public areas such as airports, shopping centers, sport clubs, and salons. A seated-massage typically lasts 10-30 minutes, and is performed while fully clothed. Seated massage is an excellent technique to use for working on the neck, shoulders and upper back areas of the body. Due to the way the individual is positioned, seated massage allows the therapist to work with the force of gravity while doing a treatment.
## Champissage
Champissage or (Indian head massage) has been used in India for centuries. It combines massage with the more subtle form of chakra balancing. It is normally done by applying oil over the body. Also called 'champi' or Maalis. The word shampoo in English usage dates back to 1762, with the meaning "to massage". The word was a loan from Anglo-Indian shampoo, in turn from Hindi chāmpo (चाँपो Template:IPA), imperative of chāmpnā (चाँपना Template:IPA), "to smear, knead the muscles, massage". It itself comes from Sanskrit/Hindi word "champā" (चम्पा Template:IPA), the flowers of the plant Michelia champaca which have traditionally been used to make fragrant hair-oil. It is often performed by the barber after a haircut on the head, shoulders, arms, and neck.
The term and service was introduced by a Bengali entrepreneur Sake Dean Mahomed, who opened a shampooing bath known as 'Mahomed's Indian Vapour Baths' in Brighton, England in 1759.
## Craniosacral therapy
Craniosacral therapy is a gentle, hands-on method of evaluating the functioning of the craniosacral system, and is often mistakenly referred to as a type of massage. It works through using the body's own self-correcting mechanisms rather than the application of physical force from the practitioner. When used by a massage practitioner, craniosacral therapy can usefully complement the massage treatment,
## Deep tissue massage
Deep tissue techniques are generally designed for more focused massage work. Working a specific joint, muscle or muscle group, the practitioner can access deeper layers of the soft tissue. Starting superficially and easing into the depth of the muscle slowly often allows more movement. If the pressure is applied too deeply or too quickly, the muscle may tighten to protect that area, and unnecessary damage or inflammation can be induced. Very little lubricant is used as the pressure doesn't travel much over the skin.
The most commonly used 'tools' during deep tissue massage may include, 3 and 6 fingers, reinforced fingers, knuckles, a flat elbow, opposing thumbs, the heel of the hand or foot, and the forearm. Deep tissue is similar to Myofascial Release.
Deep muscle therapy was created by Therese Pfrimmer of Canada.
## Horstmann technique
Practical technique that works by initially balancing the "energy field" and then holding on special energy points while mobilising limbs.
## Esalen Massage
Esalen Massage was developed by Charlotte Selver and works with gentle rocking of the body, passive joint exercises and deep structural work on the muscles and joints, together with an energetic balancing of the body.
## Infant massage
Shantala massage is an ancient Indian massage technique with a rhythmic character, given to massage babies and children. It was introduced into Western society by Dr. Frederique Leboyer, a French obstetrician.
## Lomilomi
Lomilomi is the traditional massage of Hawaii. As an indigenous practice, it varies by island and by family. The styles most known today are those of Auntie Margaret Machado of the island of Hawaii, Uncle Kalua Kaiahua of Maui and Oahu, and Kahu Abraham Kawaii of Kaua'i, who called his style Kahuna Bodywork. Other names given to massage performed in Hawaii are temple style, lomi lomi, lomi lomi nui, romi kapa rere, romi romi and ma-uri. Some of these styles may be traditional, and others may have been influenced by or created in modern times. The purported Lomilomi massage given by Barbra Streisand to Robert De Niro in "Meet the Fockers" was not an accurate representation of the style.
## Medical massage
Massage used in the medical field includes Manual lymphatic drainage used for lymphedema [5] which can be used in conjunction with the treatment of breast cancer. Carotid sinus massage is used to diagnose carotid sinus syncope and is sometimes useful for differentiating supraventricular tachycardia (SVT) from ventricular tachycardia. It, like the valsalva maneuver, is a therapy for SVT.[16] However, it is less effective than pharmaceutical management of SVT with verapamil or adenosine.[17]
## Myofascial release
Myofascial release refers to the manual massage technique for stretching the fascia and releasing bonds between fascia, integument, and muscles with the goal of eliminating pain, increasing range of motion and equilibrioception. Injuries, stress, trauma, overuse and poor posture can cause restriction to fascia. This is usually done by applying shear compression or tension in various directions, or by skin rolling. Myofascial release originators come from Physical Therapy and from Structural Integration (Rolfing); its current developers include John Barnes, Art Riggs, Michael Stanborough, Tom Myers, Til Luchau and Michael Leahy, the originator of a complete regime called Active Release Technique or ART.
Proprioceptive Neuromuscular Facilitation (PNF) and myofacial techniques are believed to lengthen tight/facilitated muscles while fiber activation techniques are believed tone weak/inhibited muscles.
## Neuromuscular therapy
Neuromuscular Therapy (NMT) is used for pain relief. Perceived imbalances in Human position are assessed initially through a postural assessment. These are then addressed through systematic and site specific massage. NMT was developed in the 1930s by Dr. Stanley Leif, current practitioners include Paul St. John.
## Nihon Kaifuku Anma - Traditional Japanese massage
Introduced to Japan about 1300 years ago. Anma is deep tissue work using no oils and is based on kneading movements. Shiatsu massage grew out of this rich tradition.
## Pregnancy massage
Doulas will often use massage in an attempt to smooth the labor process.
## Reflexology massage
Reflexology, also called Foot zone therapy, is traditionally practiced without lotion, as the pressure points on the feet are stimulated by thumb and finger walking, as well as static pressure. Foot massage practitioners believe that the ailment of an internal organ will be associated with the nerve ending on the sole of the foot. As pressure is applied to the sole, theory holds that a healthy patient should not feel any strong pain. This theory is based on a perceived energetic flow of "meridians" in the body, also known as Chi.
Before the massage, the patient's feet are soaked for about ten minutes in a foot bath, typically a solution of hot water and Chinese herbs. The practitioner rubs and massages the painful spots to break down rough spots and accumulated crystals which have not been scientifically researched. Based on this idea, some shoe liners are made with pressure points to stimulate the soles of the feet.
## Shiatsu
Shiatsu (指圧) is a form of Japanese massage that uses thumb pressure and works along the same energy meridians as acupressure and incorporates stretching. While receiving Shiatsu, you are fully clothed while laying on a mat on the floor.
## Soft tissue therapy
Treatment techniques include trigger point therapy, myofascial Release, friction for adhesions between fascial layers and muscles. Sustained finger pressure to alleviate hypertonic, or tight, areas within muscle and fascia, active Release therapies, and deep tissue massage are all derivatives of soft tissue therapy. Different types of stretching such as static stretching, dynamic stretching, and/or PNF stretching (proprioceptive neuromuscular facilitation).
Another form of Soft tissue therapy is Muscle energy technique (MET) which uses reciprocal inhibition (RI) which is when the therapist uses a client’s muscle to stretch the opposing muscle. The therapist takes the muscle that they are wishing to stretch to its full range of motion. The therapist then gets the client to use the opposing muscle by moving away from the therapist. When the client relaxes the therapist then moves the muscle in an attempt to realign the muscle fibers.
## Sports massage
A Sports Massage can be described as massage that has derived from the Swedish style massage specifically to treat sporting injuries and sports persons, pre and post-event. The same techniques of effleurage, petrissage, friction, tapotement, compression, and vibration are employed; however, the movements are often reinforced, which makes the effect much deeper, and are usually targeted towards specific muscles and tissues to treat them in isolation, as well as holistically.
A Sports Massage may involve treating the entire body, as part of a training routine, or more usually a specific area is treated due to a particular muscle strain or injury.
Due to the nature of various sports and athletic pursuits, clients may attend for treatment with recent injuries. Direct pressure over the injury site is specifically contra-indicated for 48-72 hours after the occurrence; this over and above the standard massage contra-indications.
Neuro Muscular Technique (NMT) and Muscle Energy Technique (MET) are often used by the Sports Massage Therapist to treat high degrees of tension or 'knotting' of specific muscles. These techniques are extremely useful in relaxing the muscles sufficiently to allow the therapist perform a more standard massage routine.
## Stone massage
Heated stones were used by Egyptians, Native Americans and in Lomilomi massage. Smooth hot or cold stones, usually basalt or marble, are used to massage the body. When heated stones are used, muscles relax, allowing the massage therapist to work deeper into the muscle. Energy medicine is sometimes incorporated into stone massage. Stones are heated in hot water and are placed under the back, along both sides of the spine, and on top of the torso and are believed to heat the chakra or meridians centers. Heated stones coated in oil are then used directly in the hands of the therapist delivering various massaging strokes.
## Structural Integration
Rolfing, a method of Structural Integration, works with realigning the body structurally and human gait.
## Swedish massage
This style utilizes long, flowing strokes, often but not necessarily in the direction of the heart. There are six basic strokes: effleurage from the French effleurer, 'to skim over', petrissage from the French pétrir, 'to knead', friction, tapotement, compression, and vibration. Petrissage is a kneading movement with the whole palm or finger tips, using wringing, skin rolling, compression, and/or lifting. Petrissage is usually applied vertically to the muscle tissue. Oil, cream, or lotion is applied on the skin to reduce friction and allow smooth strokes. Effleurage consists of long, flowing or gliding strokes, performed with open hands. In many massage sessions, effleurage is used as the initial type of stroking, as it has a calming effect when performed slowly. Swedish massage has shown to be helpful in reducing pain, joint stiffness, and improving function in patients with osteoarthritis of the knee over a period of eight weeks. [18]
### History
This style of massage is generally attributed to the Swedish fencing master and gymnastics teacher Per Henrik Ling (1776-1839). However, it was in fact the Dutch practitioner Johan Georg Mezger (1838-1909) who adopted the French names to denote the basic strokes. The term Swedish Movement System was transposed to Swedish Massage System sometime during the second half of the 19th century. Ling’s system was the Swedish Movement System or Swedish Gymnastic Movement System. This may be how he has become incorrectly associated for so long with Swedish massage.
[19]
## Tai Ji/Tai Chi massage
This massage uses the natural principles of Yin and Yang to achieve balance in the energies of the body. Practitioners of Tai Ji believe that it uses Tao and deals with Qi blockages.
## Thai massage
Known in Thailand as นวดแผนโบราณ (Nuat phaen boran, IPA Template:IPA), meaning "ancient/traditional massage", Thai massage is also known as Thai ancient massage, traditional Thai massage, Thai yoga massage, yoga massage, Thai classical massage, Thai bodywork, passive yoga or assisted yoga. Thai massage originated in India based and is based on Ayurveda and yoga, thereafter becoming popular in ancient Siam, now known as Thailand. It was believed that the massage art was brought over to Thailand by Shivago Komarpaj (Jivaka Kumarabhacca), a contemporary of Gautama Buddha over 2500 years ago.
The receiver is put into many yoga like positions during the course of the massage. In the northern style based out of Chiang Mai, Thailand there is a lot of stretching movements, unlike the southern style where acupressure is emphasized.
The massage recipient changes into loose, comfortable clothes and lies on a mat or firm mattress on the floor. (It can be done solo or in a group of a dozen or so patients in the same large room.) The massage practitioner leans on the recipient's body using hands and usually straight forearms locked at the elbow to apply firm rhythmic pressure. The massage generally follows the Sen lines on the body — somewhat analogous to meridians or Channel (Chinese medicine) and Indian nadis. Legs and feet of the giver can be used to fixate the body or limbs of the recipient. In other styles, hands fixate the body, while the feet do the massaging action. Oil is not used in traditional Thai Massage. A full Thai massage session typically lasts two hours or more, and includes rhythmic pressing and stretching of the entire body; this may include pulling fingers, toes, ears, cracking the knuckles, walking on the recipient's back, and arching the recipient's into bhujangasana or (cobra position). There is a standard procedure and rhythm to this massage. In Thailand a two hour massage might cost around 300 Thai baht (US $8 in 2005) depending on location (it may cost ten times more inside a five star hotel).
Note: The traditional therapeutic practice of Thai massage should not be confused with the sexual service of the same name that is available in some hotels and brothels. Sometimes the traditional therapeutic Thai Massage, or ancient massage, is referred to as "old lady massage", while the sexual practice, which has nothing to do with therapeutic traditional massage is called "young lady massage".
## Traditional Chinese massage
Tui Na (推拿) focusing on pushing, stretching and kneading the muscle. Zhi Ya (指壓) is similar to Tui Na massage except it focuses more on pinching and pressing at acupressure points. They are both based on principles from Traditional Chinese Medicine.
## Trager Approach
The Trager Approach combines movement, massage and education.
## Trigger point therapy
This can also be called pressure point massage. [5] A trigger point is an area of a muscle (about 50 cells) that may refer pain sensations to other parts of the body. Manual pressure is applied to these points. This work was founded by Dr. Janet G. Travell, U.S. President John F. Kennedy's physician and David Simons. This work can be incorporated into other styles of massage therapy such as neuromuscular therapy (NMT) or Swedish.
## Visceral manipulation
One form is Mayan abdominal massage which is practiced in many countries in Latin America. This type of massage was developed by Don Elijio Panti and Dr. Rosita Arvigo of Peru.
Mantak Chia introduced a form of abdomen massage called Chi Nei Tsang, which he teaches, helps to "clears negative emotions" (in the form of "bad winds" or "sick winds") which gather near the navel.[20]
## Watsu
Watsu is the combination of hydrotherapy and Shiatsu developed by Harold Dull in his time spent at Harbin Hot Springs near Middletown, California, USA. The work is done in skin temperature water with both the therapist and practitioner in the water, usually a pool which is between 3.5 ft to 4 ft. (100–120 cm) deep. The work entails much movement in the water and practitioners believe that it incorporates the activation of the energy lines derived from Shiatsu.
# Associated methods
Many types of practices are associated with massage and include Bodywork (alternative medicine), manual therapy, energy medicine, and breathwork. Other names for massage and related practices include hands-on work, body/somatic therapy, and somatic movement education. Body-mind integration techniques stress self-awareness and movement over physical manipulations by a practitioner. Therapies related to movement awareness/education are closer to Dance and movement therapies. Massage can also have connections with the New Age movement and alternative medicine as well as being used by mainstream medical practitioners.
# Beneficial effects
Peer-reviewed medical research has shown that the benefits of massage include pain relief, reduced trait anxiety and depression, and temporarily reduced blood pressure, heart rate, and state anxiety.[21] Theories behind what massage might do include blocking nociception (gate control theory), activating the parasympathetic nervous system which may stimulate the release of endorphins and serotonin, preventing fibrosis or scar tissue, increasing the flow of lymph, and improving sleep[5] but such effects are yet to be supported by well designed clinical studies.
Massage is hindered from reaching the gold standard of scientific research which includes placebo-controlled and double blind clinical trials.[22] [23] Developing a "sham" manual therapy for massage would be difficult since even light touch massage could not be assumed to be completely devoid of effects on the subject.[22] It would also be difficult to find a subject that would not notice that they were getting less of a massage and it would be impossible to blind the therapist.[22] Massage can employ randomized controlled trials which are published in peer reviewed medical journals.[22] This type of study could increase the credibility of the profession because it displays that purported therapeutic effects are reproducible.[23]
## Single dose effects
Pain relief:
Relief from pain due to musculoskeletal injuries and other causes is cited as a major benefit of massage.[5] In one study, cancer patients self-reported symptomatic relief of pain.[24] [25] This study, however, did not include a no treatment or placebo control group so these effect may be due to the placebo effect or regression towards the mean. Massage can also relieve tension headaches. Acupressure or pressure point massage may be more beneficial than classic Swedish massage in relieving back pain.[26] However, a meta-study conducted by scientists at the University of Illinois at Urbana-Champaign failed to find a statistically significant reduction in pain immediately following treatment. [21]
State anxiety:
Massage has been shown to reduce state anxiety, a transient measure of anxiety in a given situation. [21]
Blood pressure and heart rate:
Massage has been shown to reduce blood pressure and heart rate as temporary effects. [21]
Attention:
After massage, EEG patterns indicate enhanced performance and alertness on mathematical computations, with the effects perhaps being mediated by decreased stress hormones.
Other:
Massage also stimulates the immune system[27] by increasing peripheral blood lymphocytes (PBLs). However, this immune system effect is only observed in aromatherapy massage, which includes sweet almond oil, lavender oil, cypress oil, and sweet marjoram oil. It is unclear whether this effect persists over the long term.
## Multiple dose effects
Pain relief:
When combined with education and exercises, massage might help sub-acute, chronic, non-specific low back pain. [28] Furthermore, massage has been shown to reduce pain experienced in the days or weeks after treatment. [21]
Trait anxiety:
Massage has been shown to reduce trait anxiety; a person's general susceptibility to anxiety. [21]
Depression:
Massage has been shown to reduce subclinical depression. [21]
Diseases:
Massage, involving stretching, has been shown to help with spastic diplegia resulting from Cerebral palsy in a small pilot study.[29] The researchers warn that these results should "be viewed with caution until a double-blind controlled trial can be conducted".
Massage has been used in an effort to improve symptoms, disease progression, and quality of life in HIV patients, however, this treatment is not scientifically supported.[30]
# Regulation
In the USA there are about 90,000 massage therapists. [7] Training programs in the US are typically 500–1000 hours in length, and can award a certificate, diploma, or degree depending on the particular school. [31] There are around 1,300 programs training massage therapists in the country and study will often include anatomy and physiology, kinesiology, massage techniques, first aid and CPR, business, ethical and legal issues, and hands on practice along with continuing education requirements if regulated. [5] The Commission on Massage Therapy Accreditation (COMTA) is one of the organizations that works with massage schools in the U.S.. [6]
38 states and the District of Columbia require some type of licencing for massage therapists. [32]
In the US, 32 states use the National Certification Board for Therapeutic Massage and Bodywork's certification program as a basis for granting licenses either by rule or statute. [33] The National Board grants the designation Nationally Certified in Therapeutic Massage and Bodywork (NCTMB). There are two tests available and you can become certified through a porfolio process if you have equivalent training and experience. [34] Between 10-20% of towns or counties regulate the profession. [35] These local regulations can range from prohibition on opposite sex massage, fingerprinting and venereal checks from a doctor, to prohibition on house calls because of concern reguarding sale of sexual services.[35] [36]
In the USA licensure is the highest level of regulation and this restricts anyone without a license from practicing massage therapy or by calling themselves that protected title. Certification allows only those who meet certain educational criteria to use the protected title and registration only requires a listing of therapists who apply and meet an educational requirement. [36]
In Canada only three provinces regulate massage therapy [37] they are British Columbia, Ontario, and Newfoundland and Labrador. [35] The Canadian Massage Therapists Alliance (CMTA) has set a level of 2200 practice hours in Ontario, and Newfoundland and Labrador and 3000 hours in British Columbia. [37]
In India, massage therapy is licenced by The Department of Ayurveda, Yoga & Naturopathy, Unani, Siddha and Homoeopathy (AYUSH) under the Ministry of Health and Family Welfare (India) in March of 1995.
Because the art and science of massage is a globally diverse phenomenon, different legal jurisdictions sometimes recognize and license individuals with titles. Examples are:
- Registered Massage Therapist (RMT) Canada
- Certified Massage Therapist (CMT)
- Licensed Massage Practitioner (LMP)
- Licensed Massage Therapist (LMT)
- Licensed Massage and Bodywork Therapist (LMBT) North Carolina
# Prevalence in the United States
In 1997 there was an estimated 114 million visits to massage therapists in the US.[31] Massage therapy is the most used type of Complementary and alternative medicine in hospitals in the United States.[6]
People state that they use massage because they believe that it relieves pain from musculoskeletal injuries and other causes of pain, reduces stress and enhances relaxation, rehabilitates sports injuries, decreases feelings of anxiety and depression, and increases general well being.[5]
In a poll of 25-35 year olds 79% said they would like their health insurance plan to cover massage.[8] Some of the companies that offer massage to their employees include Allstate, Best Buy, Cisco Systems, FedEx, Gannett (which runs USA Today), General Electric, Hewlett-Packard, Home Depot, JC Penney, Kimberly-Clark, Texas Instruments and Yahoo. In 2006 Duke University Health System opened up a center to integrate medical disciplines with CAM disciplines such as massage therapy and acupuncture[38], this trend was started by Andrew Weil. There were 15,500 spas in the United States in 2007 with about a third of the visitors being men.[32]
The number of visits rose from 91 million in 1999 to 136 million in 2003, generating a revenue that equals $11 billion.[39]
# Prevalence in Asia
In Asia, bathroom attendants may provide a hot face towel and a massage.
# Notable practitioners
Heinrich Himmler, commander of the Schutzstaffel (SS) and one of the most powerful men in Nazi Germany might have lost faith in German victory due to his discussions with his masseurs Felix Kersten and Walter Schellenberg.[40]
Albert Bedane (1893–1980) who provided shelter to a Jewish woman and others during World War II was a massage/physiotherapist. | https://www.wikidoc.org/index.php/Deep_tissue_massage | |
e4196ad079d747fb076203c52866ba0d28370338 | wikidoc | Déjà vu | Déjà vu
Déjà vu (pronounced Template:Audio-IPA; French Template:Audio-IPA "already seen"; also called paramnesia, from Greek παρα para, "near" + μνήμη mnēmē, "memory") is the experience of feeling sure that one has witnessed or experienced a new situation previously (an individual feels as though an event has already happened or has repeated itself). The term was coined by a France|French psychic researcher, Émile Boirac (1851–1917) in his book L'Avenir des sciences psychiques (The Future of Psychic Sciences), which expanded upon an essay he wrote while an undergraduate. The experience of déjà vu is usually accompanied by a compelling sense of familiarity, and also a sense of "eeriness", "strangeness", or "weirdness". The "previous" experience is most frequently attributed to a dream, although in some cases there is a firm sense that the experience "genuinely happened" in the past.
The experience of déjà vu seems to be quite common among adults and children alike; in formal studies 70% of people report having experienced it at least once. References to the experience of déjà vu are also found in literature of the past, indicating it is not a new phenomenon. It has been extremely difficult to evoke the déjà vu experience in Experiment|laboratory settings, therefore making it a subject of few empirical studies. Recently, researchers have found ways to recreate this sensation using hypnosis.
# Types of déjà vu
According to Arthur Funkhouser there are three major types of déjà vu.
## Déjà vécu
Déjà vécu refers to an experience involving more than just sight, which is why labeling such "déjà vu" is usually inaccurate. The sense involves a great amount of detail, sensing that everything is just as it was before and a weird knowledge of what is going to be said or happen next.
Translated literally as 'already lived,' déjà vécu is described in a quotation from Charles Dickens:
When most people speak of déjà vu, they are actually experiencing déjà vécu. Surveys have revealed that as much as 70% of the population have had these experiences, usually between ages 15 to 25, when the mind is still subject to noticing the change in environment. The experience is usually related to a very ordinary event, but it is so striking that it is remembered for several years afterwards.
More recently, the term déjà vécu has been used to describe very intense and persistent feelings of a déjà vu type, which occur as part of a memory disorder.
## Déjà senti
This phenomenon specifies something 'already felt.' Unlike the implied precognition of déjà vécu, déjà senti is primarily or even exclusively a mental happening, has no precognitive aspects, and rarely if ever remains in the afflicted person's memory afterwards.
Dr. John Hughlings Jackson recorded the words of one of his patients who suffered from temporal lobe or psychomotor epilepsy in an 1888 paper:
As with Dr. Jackson's patient, some temporal-lobe epileptics may experience this phenomenon.
## Déjà visité
This experience is less common and involves an uncanny knowledge of a new place. The translation is "already visited." Here one may know his or her way around in a new town or landscape while at the same time knowing that this should not be possible.
Theories involving dreams, reincarnation and also Out-of-body experience|out-of-body travel have been used to explain this phenomenon. Additionally, some suggest that reading a detailed account of a place can result in this feeling when the locale is later visited. Two famous examples of such a situation were described by Nathaniel Hawthorne in his book Our Old Home and Sir Walter Scott in Guy Mannering. Hawthorne recognized the ruins of a castle in England and later was able to trace the sensation to a piece written about the castle by Alexander Pope nearly a century earlier.
C. G. Jung published an account of déjà visité in his 1952 paper On synchronicity.
In order to distinguish déjà visité from déjà vécu, it is important to identify the source of the feeling. Déjà vécu is in reference to the temporal occurrences and processes, while déjà visité has more to do with geography and spatial relations.
# Scientific research
In recent years, déjà vu has been subjected to serious psychological and neurophysiological research. Scientifically speaking, the most likely explanation of déjà vu is not that it is an act of "precognition" or "prophecy", but rather that it is an anomaly of memory; it is the impression that an experience is "being recalled". This explanation is substantiated by the fact that the sense of "recollection" at the time is strong in most cases, but that the circumstances of the "previous" experience (when, where and how the earlier experience occurred) are quite uncertain. Likewise, as time passes, subjects can exhibit a strong recollection of having the "unsettling" experience of déjà vu itself, but little to no recollection of the specifics of the event(s) or circumstance(s) they were "remembering" when they had the déjà vu experience. In particular, this may result from an overlap between the neurological systems responsible for short-term memory (events which are perceived as being in the present) and those responsible for long-term memory (events which are perceived as being in the past). In other words, the events would be stored into memory before the conscious part of the brain even receives the information and processes it. This would explain why one is, if it ever comes to mind, powerless trying to twist the outcome of the event in order to create a paradox. The delay is only of a few milliseconds, and besides, already happened at the time the consciousness of the individual is experiencing it.
Another theory being explored is that of vision. As the theory suggests, one eye may record what is seen fractionally faster than the other, creating that "strong recollection" sensation upon the "same" scene being viewed milliseconds later by the opposite eye. However, this one fails to explain the phenomenon when other sensory inputs are involved, such as the auditive part, and especially the digital part. If one, for instance, experiences déjà vu of someone slapping the fingers on his/her left hand, then the déjà vu feeling is certainly not due to his/her right hand to be late on the left one. Also, persons with only one eye still report experiencing déjà vu or déjà vecu. The global phenomenon must therefore be narrowed down to the brain itself (say, one hemisphere would be late compared to the other one).
## Links with disorders
Early researchers tried to establish a link between déjà vu and serious psychopathology such as schizophrenia, anxiety, and dissociative identity disorder, with hopes of finding the experience of some diagnostic value. However, there does not seem to be any special association between déjà vu and schizophrenia or other neurotic conditions. The strongest pathological association of déjà vu is with temporal lobe epilepsy. This correlation has led some researchers to speculate that the experience of déjà vu is possibly a neurological anomaly related to improper electrical discharge in the brain. As most people suffer a mild (i.e. non-pathological) epileptic episode regularly (e.g. the sudden "jolt", a hypnagogic jerk, that frequently occurs just prior to falling asleep), it is conjectured that a similar (mild) neurological aberration occurs in the experience of déjà vu, resulting in an erroneous sensation of memory.
## Pharmacology
It has been reported that certain drugs increase the chances of déjà vu occurring in the user. Some pharmaceutical drugs, when taken together, have also been implicated in the cause of déjà vu. Taiminen and Jääskeläinen (2001) reported the case of an otherwise healthy male who started experiencing intense and recurrent sensations of déjà vu on taking the drugs amantadine and phenylpropanolamine together to relieve flu symptoms. He found the experience so interesting that he completed the full course of his treatment and reported it to the psychologists to write-up as a case study. Due to the dopaminergic action of the drugs and previous findings from electrode stimulation of the brain (e.g. Bancaud, Brunet-Bourgin, Chauvel, & Halgren, 1994), Taiminen and Jääskeläinen speculate that déjà vu occurs as a result of hyperdopaminergic action in the mesial temporal areas of the brain.
## Memory-based explanations
The similarity between a déjà vu-eliciting stimulus and an existing, but different, memory trace may lead to the sensation. Thus, encountering something which evokes the implicit associations of an experience or sensation that cannot be remembered may lead to déjà vu. In an effort to experimentally reproduce the sensation, Banister and Zangwill (1941) used hypnosis to give participants posthypnotic amnesia for material they had already seen. When this was later re-encountered, the restricted activation caused by the posthypnotic amnesia resulted in three of the 10 participants reporting what the authors termed paramnesias. Memory-based explanations may lead to the development of a number of non-invasive experimental methods by which a long sought-after analogue of déjà vu can be reliably produced that would allow it to be tested under well-controlled experimental conditions.
Another possible explanation for the phenomenon of déjà vu is the occurrence of "cryptamnesia", which is where information learned is forgotten but nevertheless stored in the brain, and occurrence of similarities invokes the contained knowledge, leading to a feeling of familiarity because of the situation, event or emotional/vocal content, known as "déjà vu".
## Neural theories
In the late 20th and early 21st Centuries, it was widely believed that déjà vu could be caused by the mis-timing of neuronal firing. This timing error was thought to lead the brain to believe that it was encountering a stimulus for the second time, when in fact, it was simply re-experiencing the same event from a slightly delayed source. A number of variations of these theories exist, with miscommunication of the two cerebral hemispheres and abnormally fast neuronal firing also given as explanations for the sensation.
## Parapsychology
Déjà vu is associated with precognition, clairvoyance or extra-sensory perceptions, and it is frequently cited as evidence for "psychic" abilities in the general population. Non-scientific explanations attribute the experience to prophecy, visions (such as received in dreams) or past-life memories.
## Dreams
Some believe déjà vu is the memory of dreams. Though the majority of dreams are never remembered, a dreaming person can display activity in the areas of the brain that process long-term memory. It has been speculated that dreams read directly into long-term memory, bypassing short-term memory entirely. In this case, déjà vu might be a memory of a forgotten dream with elements in common with the current waking experience. This may be similar to another phenomenon known as déjà rêvé, or "already dreamed." However, later studies on mice indicate that long-term memories must be first established as short-term memories.
Not only is the link to dreams as they pertain to déjà vu the subject of scientific and psychological studies, it is also a subject of spiritual texts, as is found, for example, in the writings of the Bahá'í Faith with quotes like "... perchance when ten years are gone, thou wilt witness in the outer world the very things thou hast dreamed tonight." and "Behold how the thing which thou hast seen in thy dream is, after a considerable lapse of time, fully realized."
Daniel Heady suggested that a feeling of remembering occurs in a sense that a he might realize that what he had dreamt is now a relevant present action that is taking place right here right now.
"I was once sitting down in the kitchen noticing that my plate seemed well too familiar, it seemed as if my head motions were foreseen, and that every move would trigger a continuation to happen or so, I had many déjà vu's as a child but this was extraordinary, I knew from the bottom of my heart that I had dreamed this situation years ago, as a little boy, that amazingly an entire piece of memory was regained and I finally understood when and where I was dreaming and how long this dream was, and most importantly how many years ago did I dream."Template:Who
## Reincarnation
Those believing in reincarnation theorize that déjà vu is caused by fragments of past-life memories being jarred to the surface of the mind by familiar surroundings or people. Others theorize that the phenomenon is caused by astral projection, or out-of-body experiences (OBEs), where it is possible that individuals have visited places while in their astral bodies during sleep. The sensation may also be interpreted as connected to the fulfillment of a condition as seen or felt in a premonition. For further cases of remembering information from past lives, see Ian Stevenson.
# Related phenomena
## Jamais vu
Jamais vu is a term in psychology (from the French, meaning "never seen") which is used to describe any familiar situation which is not recognized by the observer.
Often described as the opposite of déjà vu, jamais vu involves a sense of eeriness and the observer's impression of seeing the situation for the first time, despite rationally knowing that he or she has been in the situation before.
Jamais vu is more commonly explained as when a person momentarily does not recognize a word, person, or place that they already know.
Jamais vu is sometimes associated with certain types of amnesia and epilepsy.
Theoretically, as seen below, a jamais vu feeling in a sufferer of a delirious disorder or intoxication could result in a delirious explanation of it, such as in the Capgras delusion, in which the patient takes a person known by him/her for a false double or impostor. If the impostor is himself, the clinical setting would be the same as the one described as depersonalisation, hence jamais vus of oneself or of the very "reality of reality", are termed depersonalisation (or irreality) feelings.
Times Online reports:
## Tip of Tongue (Presque vu)
Déjà vu is similar to, but distinct from, the phenomenon called tip of the tongue which is when one cannot recall a familiar word or name or situation, but with effort one eventually recall the elusive memory. In contrast, déjà vu is a feeling that the present situation has occurred before, but the details are elusive because the situation never happened before.
Presque vu (from French, meaning "almost seen") is the sensation of being on the brink of an epiphany (feeling)|epiphany. Often very disorienting and distracting, presque vu rarely leads to an actual breakthrough. Frequently, one experiencing presque vu will say that they have something "on the tip of their tongue."
Presque vu is often cited by people who suffer from epilepsy or other seizure-related brain conditions, such as temporal lobe lability.
## L'esprit de l'escalier
L'esprit de l'escalier (from French, "staircase wit") is remembering something when it is too late. For example, a clever come-back to a remark, thought of after the conversation has ended.
An example of L'esprit de l'escalier in popular culture can be seen in the TV sitcom Seinfeld. In one episode, the character George Costanza thinks of a perfect comeback-line to an insult he received from a co-worker, but too late to deliver it. While George is rapidly consuming a bowl of shrimp during an office meeting, a co-worker teases him, saying "Hey George, the ocean called. It's running out of shrimp". Only later in the day does George conceive of the perfect comeback: "Well, the jerk store called. They're running out of you." | Déjà vu
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Déjà vu (pronounced Template:Audio-IPA; French Template:Audio-IPA "already seen"; also called paramnesia, from Greek παρα para, "near" + μνήμη mnēmē, "memory") is the experience of feeling sure that one has witnessed or experienced a new situation previously (an individual feels as though an event has already happened or has repeated itself). The term was coined by a France|French psychic researcher, Émile Boirac (1851–1917) in his book L'Avenir des sciences psychiques (The Future of Psychic Sciences), which expanded upon an essay he wrote while an undergraduate. The experience of déjà vu is usually accompanied by a compelling sense of familiarity, and also a sense of "eeriness", "strangeness", or "weirdness". The "previous" experience is most frequently attributed to a dream, although in some cases there is a firm sense that the experience "genuinely happened" in the past.
The experience of déjà vu seems to be quite common among adults and children alike; in formal studies 70% of people report having experienced it at least once. References to the experience of déjà vu are also found in literature of the past, indicating it is not a new phenomenon. It has been extremely difficult to evoke the déjà vu experience in Experiment|laboratory settings, therefore making it a subject of few empirical studies. Recently, researchers have found ways to recreate this sensation using hypnosis.[1]
# Types of déjà vu
According to Arthur Funkhouser there are three major types of déjà vu.[2]
## Déjà vécu
Déjà vécu refers to an experience involving more than just sight, which is why labeling such "déjà vu" is usually inaccurate. The sense involves a great amount of detail, sensing that everything is just as it was before and a weird knowledge of what is going to be said or happen next.
Translated literally as 'already lived,' déjà vécu is described in a quotation from Charles Dickens:
When most people speak of déjà vu, they are actually experiencing déjà vécu. Surveys have revealed that as much as 70% of the population have had these experiences, usually between ages 15 to 25[4], when the mind is still subject to noticing the change in environment. The experience is usually related to a very ordinary event, but it is so striking that it is remembered for several years afterwards.
More recently, the term déjà vécu has been used to describe very intense and persistent feelings of a déjà vu type, which occur as part of a memory disorder.[5]
## Déjà senti
This phenomenon specifies something 'already felt.' Unlike the implied precognition of déjà vécu, déjà senti is primarily or even exclusively a mental happening, has no precognitive aspects, and rarely if ever remains in the afflicted person's memory afterwards.
Dr. John Hughlings Jackson recorded the words of one of his patients who suffered from temporal lobe or psychomotor epilepsy in an 1888 paper:
As with Dr. Jackson's patient, some temporal-lobe epileptics may experience this phenomenon.
## Déjà visité
This experience is less common and involves an uncanny knowledge of a new place. The translation is "already visited." Here one may know his or her way around in a new town or landscape while at the same time knowing that this should not be possible.
Theories involving dreams, reincarnation and also Out-of-body experience|out-of-body travel have been used to explain this phenomenon. Additionally, some suggest that reading a detailed account of a place can result in this feeling when the locale is later visited. Two famous examples of such a situation were described by Nathaniel Hawthorne in his book Our Old Home[7] and Sir Walter Scott in Guy Mannering.[8] Hawthorne recognized the ruins of a castle in England and later was able to trace the sensation to a piece written about the castle by Alexander Pope nearly a century earlier.
C. G. Jung published an account of déjà visité in his 1952 paper On synchronicity.[9]
In order to distinguish déjà visité from déjà vécu, it is important to identify the source of the feeling. Déjà vécu is in reference to the temporal occurrences and processes, while déjà visité has more to do with geography and spatial relations.
# Scientific research
In recent[when?] years, déjà vu has been subjected to serious psychological and neurophysiological research. Scientifically speaking, the most likely explanation of déjà vu is not that it is an act of "precognition" or "prophecy", but rather that it is an anomaly of memory; it is the impression that an experience is "being recalled".[citation needed] This explanation is substantiated by the fact that the sense of "recollection" at the time is strong in most cases, but that the circumstances of the "previous" experience (when, where and how the earlier experience occurred) are quite uncertain. Likewise, as time passes, subjects can exhibit a strong recollection of having the "unsettling" experience of déjà vu itself, but little to no recollection of the specifics of the event(s) or circumstance(s) they were "remembering" when they had the déjà vu experience. In particular, this may result from an overlap between the neurological systems responsible for short-term memory (events which are perceived as being in the present) and those responsible for long-term memory (events which are perceived as being in the past). In other words, the events would be stored into memory before the conscious part of the brain even receives the information and processes it. This would explain why one is, if it ever comes to mind, powerless trying to twist the outcome of the event in order to create a paradox. The delay is only of a few milliseconds, and besides, already happened at the time the consciousness of the individual is experiencing it.
Another theory being explored is that of vision. As the theory suggests, one eye may record what is seen fractionally faster than the other, creating that "strong recollection" sensation upon the "same" scene being viewed milliseconds later by the opposite eye. However, this one fails to explain the phenomenon when other sensory inputs are involved, such as the auditive part, and especially the digital part. If one, for instance, experiences déjà vu of someone slapping the fingers on his/her left hand, then the déjà vu feeling is certainly not due to his/her right hand to be late on the left one. Also, persons with only one eye still report experiencing déjà vu or déjà vecu. The global phenomenon must therefore be narrowed down to the brain itself (say, one hemisphere would be late compared to the other one).
## Links with disorders
Early researchers tried to establish a link between déjà vu and serious psychopathology such as schizophrenia, anxiety, and dissociative identity disorder, with hopes of finding the experience of some diagnostic value. However, there does not seem to be any special association between déjà vu and schizophrenia or other neurotic conditions.[10] The strongest pathological association of déjà vu is with temporal lobe epilepsy.[11][4] This correlation has led some researchers to speculate that the experience of déjà vu is possibly a neurological anomaly related to improper electrical discharge in the brain. As most people suffer a mild (i.e. non-pathological) epileptic episode regularly (e.g. the sudden "jolt", a hypnagogic jerk, that frequently occurs just prior to falling asleep), it is conjectured that a similar (mild) neurological aberration occurs in the experience of déjà vu, resulting in an erroneous sensation of memory.
## Pharmacology
It has been reported that certain drugs increase the chances of déjà vu occurring in the user. Some pharmaceutical drugs, when taken together, have also been implicated in the cause of déjà vu. Taiminen and Jääskeläinen (2001) reported the case of an otherwise healthy male who started experiencing intense and recurrent sensations of déjà vu on taking the drugs amantadine and phenylpropanolamine together to relieve flu symptoms. He found the experience so interesting that he completed the full course of his treatment and reported it to the psychologists to write-up as a case study. Due to the dopaminergic action of the drugs and previous findings from electrode stimulation of the brain (e.g. Bancaud, Brunet-Bourgin, Chauvel, & Halgren, 1994), Taiminen and Jääskeläinen speculate that déjà vu occurs as a result of hyperdopaminergic action in the mesial temporal areas of the brain.
## Memory-based explanations
The similarity between a déjà vu-eliciting stimulus and an existing, but different, memory trace may lead to the sensation. Thus, encountering something which evokes the implicit associations of an experience or sensation that cannot be remembered may lead to déjà vu. In an effort to experimentally reproduce the sensation, Banister and Zangwill (1941) used hypnosis to give participants posthypnotic amnesia for material they had already seen. When this was later re-encountered, the restricted activation caused by the posthypnotic amnesia resulted in three of the 10 participants reporting what the authors termed paramnesias. Memory-based explanations may lead to the development of a number of non-invasive experimental methods by which a long sought-after analogue of déjà vu can be reliably produced that would allow it to be tested under well-controlled experimental conditions.
Another possible explanation for the phenomenon of déjà vu is the occurrence of "cryptamnesia", which is where information learned is forgotten but nevertheless stored in the brain, and occurrence of similarities invokes the contained knowledge, leading to a feeling of familiarity because of the situation, event or emotional/vocal content, known as "déjà vu".
## Neural theories
In the late 20th and early 21st Centuries, it was widely believed that déjà vu could be caused by the mis-timing of neuronal firing. This timing error was thought to lead the brain to believe that it was encountering a stimulus for the second time, when in fact, it was simply re-experiencing the same event from a slightly delayed source. A number of variations of these theories exist, with miscommunication of the two cerebral hemispheres and abnormally fast neuronal firing also given as explanations for the sensation.
## Parapsychology
Déjà vu is associated with precognition, clairvoyance or extra-sensory perceptions, and it is frequently cited as evidence for "psychic" abilities in the general population. Non-scientific explanations attribute the experience to prophecy, visions (such as received in dreams) or past-life memories.
## Dreams
Some believe déjà vu is the memory of dreams. Though the majority of dreams are never remembered, a dreaming person can display activity in the areas of the brain that process long-term memory. It has been speculated that dreams read directly into long-term memory, bypassing short-term memory entirely. In this case, déjà vu might be a memory of a forgotten dream with elements in common with the current waking experience. This may be similar to another phenomenon known as déjà rêvé, or "already dreamed." However, later studies on mice indicate that long-term memories must be first established as short-term memories.
Not only is the link to dreams as they pertain to déjà vu the subject of scientific and psychological studies, it is also a subject of spiritual texts, as is found, for example, in the writings of the Bahá'í Faith with quotes like "... perchance when ten years are gone, thou wilt witness in the outer world the very things thou hast dreamed tonight."[12] and "Behold how the thing which thou hast seen in thy dream is, after a considerable lapse of time, fully realized."[13]
Daniel Heady suggested that a feeling of remembering occurs in a sense that a he might realize that what he had dreamt is now a relevant present action that is taking place right here right now.
"I was once sitting down in the kitchen noticing that my plate seemed well too familiar, it seemed as if my head motions were foreseen, and that every move would trigger a continuation to happen or so, I had many déjà vu's as a child but this was extraordinary, I knew from the bottom of my heart that I had dreamed this situation years ago, as a little boy, that amazingly an entire piece of memory was regained and I finally understood when and where I was dreaming and how long this dream was, and most importantly how many years ago did I dream."Template:Who
## Reincarnation
Those believing in reincarnation theorize that déjà vu is caused by fragments of past-life memories being jarred to the surface of the mind by familiar surroundings or people. Others theorize that the phenomenon is caused by astral projection, or out-of-body experiences (OBEs), where it is possible that individuals have visited places while in their astral bodies during sleep. The sensation may also be interpreted as connected to the fulfillment of a condition as seen or felt in a premonition. For further cases of remembering information from past lives, see Ian Stevenson.
# Related phenomena
## Jamais vu
Jamais vu is a term in psychology (from the French, meaning "never seen") which is used to describe any familiar situation which is not recognized by the observer.
Often described as the opposite of déjà vu, jamais vu involves a sense of eeriness and the observer's impression of seeing the situation for the first time, despite rationally knowing that he or she has been in the situation before.
Jamais vu is more commonly explained as when a person momentarily does not recognize a word, person, or place that they already know.
Jamais vu is sometimes associated with certain types of amnesia and epilepsy.
Theoretically, as seen below, a jamais vu feeling in a sufferer of a delirious disorder or intoxication could result in a delirious explanation of it, such as in the Capgras delusion, in which the patient takes a person known by him/her for a false double or impostor. If the impostor is himself, the clinical setting would be the same as the one described as depersonalisation, hence jamais vus of oneself or of the very "reality of reality", are termed depersonalisation (or irreality) feelings.
Times Online reports:
## Tip of Tongue (Presque vu)
Déjà vu is similar to, but distinct from, the phenomenon called tip of the tongue which is when one cannot recall a familiar word or name or situation, but with effort one eventually recall the elusive memory. In contrast, déjà vu is a feeling that the present situation has occurred before, but the details are elusive because the situation never happened before.
Presque vu (from French, meaning "almost seen") is the sensation of being on the brink of an epiphany (feeling)|epiphany. Often very disorienting and distracting, presque vu rarely leads to an actual breakthrough. Frequently, one experiencing presque vu will say that they have something "on the tip of their tongue."
Presque vu is often cited by people who suffer from epilepsy or other seizure-related brain conditions, such as temporal lobe lability.
## L'esprit de l'escalier
L'esprit de l'escalier (from French, "staircase wit") is remembering something when it is too late. For example, a clever come-back to a remark, thought of after the conversation has ended.
An example of L'esprit de l'escalier in popular culture can be seen in the TV sitcom Seinfeld. In one episode, the character George Costanza thinks of a perfect comeback-line to an insult he received from a co-worker, but too late to deliver it. While George is rapidly consuming a bowl of shrimp during an office meeting, a co-worker teases him, saying "Hey George, the ocean called. It's running out of shrimp". Only later in the day does George conceive of the perfect comeback: "Well, the jerk store called. They're running out of you." | https://www.wikidoc.org/index.php/Deja_vu | |
3301c9fff29111eff4ce2a3b8e8ca2c8997bb109 | wikidoc | Demodex | Demodex
Demodex is a genus of tiny parasitic mites that live in or near hair follicles of mammals. About 65 species of Demodex mites are known; they are among the smallest of arthropods. Two species living on humans have been identified: Demodex folliculorum and Demodex brevis, both frequently referred to as eyelash mites. Demodex canis lives on the domestic dog. Infestation with Demodex mites is common and usually does not cause any symptoms; occasionally some skin diseases can be caused by the mites.
# Demodex folliculorum and Demodex brevis
Demodex folliculorum and Demodex brevis are the only Demodex mites that have been found on humans. D. folliculorum was first described in 1842 by Simon; D. brevis was identified as separate in 1963 by Akbulatova. D. folliculorum is found in hair follicles, while D. brevis lives in sebaceous glands connected to hair follicles. Both species are primarily found in the face, near the nose, the eyelashes and eyebrows, but also occur elsewhere on the body.
The adult mites are only between 0.3 mm and 0.4 mm long, with D. brevis slighly shorter than D. folliculorum. They have a semi-transparent elongated body that consists of two fused segments. Eight short segmented legs are attached to the first body segment. The body is covered with scales for anchoring itself in the hair follicle, and the mite has pin-like mouth-parts for eating skin-cells, hormones and oils (sebum) which accumulate in the hair follicles. The mite's digestive system is so efficient and results in so little waste that there is no excretory orifice. The mites can leave the hair follicles and slowly walk around on the skin, at a speed of about 8–16 cm/hour, especially at night; they try to avoid light.
Female Demodex folliculorum are somewhat shorter and rounder than males. The total lifespan of a Demodex mite is several weeks. Both male and female Demodex mites have a genital opening, and fertilization is internal.
Mating takes place in the follicle opening, and eggs are laid inside the hair follicles or sebaceous glands. The six-legged larvae hatch after 3-4 days, and it takes about seven days for the larvae to develop into adults. The dead mites decompose inside the hair follicles or sebaceous glands.
Older people are much more likely to carry the mites; estimates range as high as an 96-98% infestation rate in aged people. The lower rate of children may be due to the fact that children produce much less sebum. It is quite easy to look for one's own demodex mites, by carefully removing an eyelash or eyebrow hair and placing it under a microscope.
The mites are transferred between hosts through contact of hair, eyebrows and of the sebaceous glands on the nose. Different species of animals host different species of demodex; and demodex is not contagious between different species.
In the vast majority of cases, the mites go unobserved, without any adverse symptoms, but in certain cases (usually related to a suppressed immune system, caused by stress or illness) mite populations can dramatically increase, resulting in a condition known as demodicosis, characterised by itching, inflammation and other skin disorders. Blepharitis (inflammation of the eyelids) can also be caused by Demodex mites.
There is some evidence linking demodex mites to some forms of the skin disease rosacea, possibly due to the bacterium Bacillus oleronius found in the mites. Some people believe that there is also a link to acne vulgaris, but there is little research to back this up, and quite reasonable experimental evidence linking acne vulgaris to a sensitivity to Propionibacterium acnes.
# Demodex canis
The species Demodex canis lives only on the domestic dog. While, like with humans, most dogs live with their mites without harm, a minority do not have immune systems capable of completely controlling the mites, leading to a potentially dangerous infestation called demodectic mange. While direct treatment for severe cases is possible using a drug known as Mitaban which is applied to the skin, improved nutrition and checking for other, immune-system suppressing diseases are also recommended. | Demodex
Demodex is a genus of tiny parasitic mites that live in or near hair follicles of mammals. About 65 species of Demodex mites are known; they are among the smallest of arthropods. Two species living on humans have been identified: Demodex folliculorum and Demodex brevis, both frequently referred to as eyelash mites. Demodex canis lives on the domestic dog. Infestation with Demodex mites is common and usually does not cause any symptoms; occasionally some skin diseases can be caused by the mites.
# Demodex folliculorum and Demodex brevis
Demodex folliculorum and Demodex brevis are the only Demodex mites that have been found on humans. D. folliculorum was first described in 1842 by Simon; D. brevis was identified as separate in 1963 by Akbulatova. D. folliculorum is found in hair follicles, while D. brevis lives in sebaceous glands connected to hair follicles. Both species are primarily found in the face, near the nose, the eyelashes and eyebrows, but also occur elsewhere on the body.
The adult mites are only between 0.3 mm and 0.4 mm long, with D. brevis slighly shorter than D. folliculorum.[1] They have a semi-transparent elongated body that consists of two fused segments. Eight short segmented legs are attached to the first body segment. The body is covered with scales for anchoring itself in the hair follicle, and the mite has pin-like mouth-parts for eating skin-cells, hormones and oils (sebum) which accumulate in the hair follicles. The mite's digestive system is so efficient and results in so little waste that there is no excretory orifice. The mites can leave the hair follicles and slowly walk around on the skin, at a speed of about 8–16 cm/hour, especially at night; they try to avoid light.[1]
Female Demodex folliculorum are somewhat shorter and rounder than males. The total lifespan of a Demodex mite is several weeks. Both male and female Demodex mites have a genital opening, and fertilization is internal.[2]
Mating takes place in the follicle opening, and eggs are laid inside the hair follicles or sebaceous glands. The six-legged larvae hatch after 3-4 days, and it takes about seven days for the larvae to develop into adults. The dead mites decompose inside the hair follicles or sebaceous glands.
Older people are much more likely to carry the mites; estimates range as high as an 96-98% infestation rate in aged people. The lower rate of children may be due to the fact that children produce much less sebum. It is quite easy to look for one's own demodex mites, by carefully removing an eyelash or eyebrow hair and placing it under a microscope.
The mites are transferred between hosts through contact of hair, eyebrows and of the sebaceous glands on the nose. Different species of animals host different species of demodex; and demodex is not contagious between different species.
In the vast majority of cases, the mites go unobserved, without any adverse symptoms, but in certain cases (usually related to a suppressed immune system, caused by stress or illness) mite populations can dramatically increase, resulting in a condition known as demodicosis, characterised by itching, inflammation and other skin disorders. Blepharitis (inflammation of the eyelids) can also be caused by Demodex mites.
There is some evidence linking demodex mites to some forms of the skin disease rosacea, possibly due to the bacterium Bacillus oleronius found in the mites.[3] Some people believe that there is also a link to acne vulgaris, but there is little research to back this up, and quite reasonable experimental evidence linking acne vulgaris to a sensitivity to Propionibacterium acnes.
# Demodex canis
The species Demodex canis lives only on the domestic dog. While, like with humans, most dogs live with their mites without harm, a minority do not have immune systems capable of completely controlling the mites, leading to a potentially dangerous infestation called demodectic mange. While direct treatment for severe cases is possible using a drug known as Mitaban which is applied to the skin, improved nutrition and checking for other, immune-system suppressing diseases are also recommended. | https://www.wikidoc.org/index.php/Demodex | |
7c7a9cd44ef6961b8b219b731e483c4660a6ba18 | wikidoc | Density | Density
# Overview
In physics, density is mass m per unit volume V—how heavy something is compared to its size. A small, heavy object, such as a rock or a lump of lead, is denser than a lighter object of the same size or a larger object of the same weight, such as pieces of cork or foam.
For the common case of a homogeneous substance, density is expressed as:
where, in SI Units:
# History
In a famous problem, Archimedes was given the task of determining if King Hiero's goldsmith was embezzling gold during the manufacture of the king's crown and replacing it with another, cheaper alloy.
Archimedes knew that the crown could be smashed into a cube or sphere, where the volume could be calculated more easily when compared with the weight; the king did not approve of this.
Baffled, Archimedes went to take a bath and observed from the rise of the water upon entering that he could calculate the volume of the crown through the displacement of the water. Allegedly, upon this discovery Archimedes went running though the streets naked shouting, "Eureka! Eureka!" Greek for "I've found it!"
Following a test of the crown based upon this new discovery, the goldsmith was executed.
# Measurement of density
For a homogeneous object, the formula mass/volume may be used. The mass is normally measured with an appropriate scale; the volume may be measured directly (from the geometry of the object) or by the displacement of a liquid. A very common instrument for the direct measurement of the density of a liquid is the hydrometer. A less common device for measuring fluid density is a pycnometer, a similar device for measuring the absolute density of a solid is a gas pycnometer.
The density of a solid material can be ambiguous, depending on exactly how it is defined, and this may cause confusion in measurement. A common example is sand: if gently filled into a container, the density will be small; when the same sand is compacted into the same container, it will occupy less volume and consequently carry a greater density. This is because "sand" contains a lot of air space in between individual grains; this overall density is called the bulk density, which differs significantly from the density of an individual grain of sand.
# Common units
In U.S. customary units or Imperial units, the units of density include:
# Changes of density
In general density can be changed by changing either the pressure or the temperature. Increasing the pressure will always increase the density of a material. Increasing the temperature generally decreases the density, but there are notable exceptions to this generalisation. For example, the density of water increases between its melting point at 0 °C and 4 °C and similar behaviour is observed in silicon at low temperatures.
The effect of pressure and temperature on the densities of liquids and solids is small so that a typical compressibility for a liquid or solid is 10–6 bar–1 (1 bar=0.1 MPa) and a typical thermal expansivity is 10–5 K–1.
In contrast, the density of gases is strongly affected by pressure. Boyle's law says that the density of an ideal gas is given by
where R is the universal gas constant, P is the pressure, m the molar mass, and T the absolute temperature.
This means that a gas at 300 K and 1 bar will have its density doubled by increasing the pressure to 2 bar or by reducing the temperature to 150 K.
# Density of water
# Density of air
# Books
- Fundamentals of Aerodynamics Second Edition, McGraw-Hill, John D. Anderson, Jr.
- Fundamentals of Fluid Mechanics Wiley, B.R. Munson, D.F. Young & T.H. Okishi
- Introduction to Fluid Mechanics Fourth Edition, Wiley, SI Version, R.W. Fox & A.T. McDonald
- Thermodynamics: An Engineering Approach Second Edition, McGraw-Hill, International Edition, Y.A. Cengel & M.A. Boles | Density
# Overview
In physics, density is mass m per unit volume V—how heavy something is compared to its size. A small, heavy object, such as a rock or a lump of lead, is denser than a lighter object of the same size or a larger object of the same weight, such as pieces of cork or foam.
For the common case of a homogeneous substance, density is expressed as:
where, in SI Units:
# History
In a famous problem, Archimedes was given the task of determining if King Hiero's goldsmith was embezzling gold during the manufacture of the king's crown and replacing it with another, cheaper alloy.[1]
Archimedes knew that the crown could be smashed into a cube or sphere, where the volume could be calculated more easily when compared with the weight; the king did not approve of this.
Baffled, Archimedes went to take a bath and observed from the rise of the water upon entering that he could calculate the volume of the crown through the displacement of the water. Allegedly, upon this discovery Archimedes went running though the streets naked shouting, "Eureka! Eureka!" Greek for "I've found it!"
Following a test of the crown based upon this new discovery, the goldsmith was executed.
# Measurement of density
For a homogeneous object, the formula mass/volume may be used. The mass is normally measured with an appropriate scale; the volume may be measured directly (from the geometry of the object) or by the displacement of a liquid. A very common instrument for the direct measurement of the density of a liquid is the hydrometer. A less common device for measuring fluid density is a pycnometer, a similar device for measuring the absolute density of a solid is a gas pycnometer.
The density of a solid material can be ambiguous, depending on exactly how it is defined, and this may cause confusion in measurement. A common example is sand: if gently filled into a container, the density will be small; when the same sand is compacted into the same container, it will occupy less volume and consequently carry a greater density. This is because "sand" contains a lot of air space in between individual grains; this overall density is called the bulk density, which differs significantly from the density of an individual grain of sand.
# Common units
In U.S. customary units or Imperial units, the units of density include:
# Changes of density
In general density can be changed by changing either the pressure or the temperature. Increasing the pressure will always increase the density of a material. Increasing the temperature generally decreases the density, but there are notable exceptions to this generalisation. For example, the density of water increases between its melting point at 0 °C and 4 °C and similar behaviour is observed in silicon at low temperatures.
The effect of pressure and temperature on the densities of liquids and solids is small so that a typical compressibility for a liquid or solid is 10–6 bar–1 (1 bar=0.1 MPa) and a typical thermal expansivity is 10–5 K–1.
In contrast, the density of gases is strongly affected by pressure. Boyle's law says that the density of an ideal gas is given by
where <math>R</math> is the universal gas constant, <math>P</math> is the pressure, <math>m</math> the molar mass, and <math>T</math> the absolute temperature.
This means that a gas at 300 K and 1 bar will have its density doubled by increasing the pressure to 2 bar or by reducing the temperature to 150 K.
# Density of water
# Density of air
# Books
- Fundamentals of Aerodynamics Second Edition, McGraw-Hill, John D. Anderson, Jr.
- Fundamentals of Fluid Mechanics Wiley, B.R. Munson, D.F. Young & T.H. Okishi
- Introduction to Fluid Mechanics Fourth Edition, Wiley, SI Version, R.W. Fox & A.T. McDonald
- Thermodynamics: An Engineering Approach Second Edition, McGraw-Hill, International Edition, Y.A. Cengel & M.A. Boles | https://www.wikidoc.org/index.php/Density | |
918b7446f78e5cebcbeabafe90f96cb32c736e6c | wikidoc | Dentrix | Dentrix
# Overview
Dentrix Dental Systems, a division of Sullivan-Schein Dental, sells and supports DENTRIX and Easy Dental (dental practice management software). Dentrix was the first practice management software for Windows in 1989. Dentrix Dental Systems was founded in 1985, and was incorporated in 1989. DENTRIX and Henry Schein have enjoyed a successful exclusive distribution partnership since 2005.
Dentrix uses a C-tree database system with theoretical limit of 29 workstations. The Enterprise version (DXOne) uses a SQL database and can support many workstations and/or multiple office locations. Dentrix Encourages use of 'integrated' products by purposely trying to lock out the use of other electronic claim clearinghouses. The bridge to Care Credit has been discontinued. In addition to their fully integrated digital imaging program (Dentrix Image), Dentrix allows integration with many different image software through use of DtxLinks. Images and documents are all stored in a proprietary format. Some disadvantages of the software include: being unable to mix insurance information between families, making divorce situations difficult; and difficulty splitting payments between family members.
The following is a basic list of some of the software features:
- scheduling
- accounting
- Charting
- Patient Picture
- Audit Trail
- Auto phone dialing
- Connectivity to Palm OS through DXMobile
- Ability to track Lab cases
- Voice software for periocharting
- Document Center to scan and store paperwork.
- Letter merge
- Custom Report lists.
- Digital radiographs and intra/extra oral
- payment/fee schedules
- Extensive treatment planning options with phases or alternative options
- Many Chart views (upper, lower, quadrant, side of mouth, arch and 3D modeling)
- Create multiple treatment plans
- Generate dynamic presentations based on the selected treatment plan
- Integrate relevant digital images into patient treatment plan presentations
- Burn a presentation to CD for your patient to take home
- Layout changes can be saved and applied according to the user who is logged in
- Choose from 70 new Clinical Note templates or create templates of your own
- View image thumbnails in multiple sizes
- digitally capture a patient’s signature on informed consent form.
# External websites
- ADA Vendor Directory of Practice Management Software
- Dentrix | Dentrix
# Overview
Template:Infobox Software
Dentrix Dental Systems, a division of Sullivan-Schein Dental, sells and supports DENTRIX and Easy Dental (dental practice management software). Dentrix was the first practice management software for Windows in 1989. Dentrix Dental Systems was founded in 1985, and was incorporated in 1989. DENTRIX and Henry Schein have enjoyed a successful exclusive distribution partnership since 2005.
Dentrix uses a C-tree database system with theoretical limit of 29 workstations. The Enterprise version (DXOne) uses a SQL database and can support many workstations and/or multiple office locations. Dentrix Encourages use of 'integrated' products by purposely trying to lock out the use of other electronic claim clearinghouses. The bridge to Care Credit has been discontinued. In addition to their fully integrated digital imaging program (Dentrix Image), Dentrix allows integration with many different image software through use of DtxLinks. Images and documents are all stored in a proprietary format. Some disadvantages of the software include: being unable to mix insurance information between families, making divorce situations difficult; and difficulty splitting payments between family members.
The following is a basic list of some of the software features:
- scheduling
- accounting
- Charting
- Patient Picture
- Audit Trail
- Auto phone dialing
- Connectivity to Palm OS through DXMobile
- Ability to track Lab cases
- Voice software for periocharting
- Document Center to scan and store paperwork.
- Letter merge
- Custom Report lists.
- Digital radiographs and intra/extra oral
- payment/fee schedules
- Extensive treatment planning options with phases or alternative options
- Many Chart views (upper, lower, quadrant, side of mouth, arch and 3D modeling)
- Create multiple treatment plans
- Generate dynamic presentations based on the selected treatment plan
- Integrate relevant digital images into patient treatment plan presentations
- Burn a presentation to CD for your patient to take home
- Layout changes can be saved and applied according to the user who is logged in
- Choose from 70 new Clinical Note templates or create templates of your own
- View image thumbnails in multiple sizes
- digitally capture a patient’s signature on informed consent form.
# External websites
- ADA Vendor Directory of Practice Management Software
- Dentrix | https://www.wikidoc.org/index.php/Dentrix | |
114d2f894af17bfc700c3e8b5d9a54fa126c53a0 | wikidoc | Destrin | Destrin
Destrin or DSTN (also known as actin depolymerizing factor or ADF) is a protein which in humans is encoded by the DSTN gene. Destrin is a component protein in microfilaments.
The product of this gene belongs to the actin-binding proteins ADF (Actin-Depolymerizing Factor)/cofilin family. This family of proteins is responsible for enhancing the turnover rate of actin in vivo. This gene encodes the actin depolymerizing protein that severs actin filaments (F-actin) and binds to actin monomers (G-actin). Two transcript variants encoding distinct isoforms have been identified for this gene.
# Structure
The tertiary structure of destrin was determined by the use of triple-resonance multidimensional nuclear magnetic resonance, NMR. The secondary and tertiary structures of destrin are similar to the gelsolin family which is another actin-regulating protein family.
There are three ordered layers to destrin which is a globular protein. There is a central β sheet that is composed of one parallel strand and three antiparallel strands. This β sheet is between a long α helix along with a shorter one and two shorter helices on the opposite side. The four helices are parallel to the β strands.
# Function
In a variety of eukaryotes, destrin regulates actin in the cytoskeleton. Destrin binds actin and is thought to connect it as gelsolin segment-1 does. Furthermore, the binding of actin by destrin and cofilin is regulated negatively by phosphorylation. Destrin can also sever actin filaments. | Destrin
Destrin or DSTN (also known as actin depolymerizing factor or ADF) is a protein which in humans is encoded by the DSTN gene.[2][3][4] Destrin is a component protein in microfilaments.
The product of this gene belongs to the actin-binding proteins ADF (Actin-Depolymerizing Factor)/cofilin family. This family of proteins is responsible for enhancing the turnover rate of actin in vivo. This gene encodes the actin depolymerizing protein that severs actin filaments (F-actin) and binds to actin monomers (G-actin). Two transcript variants encoding distinct isoforms have been identified for this gene.[2]
# Structure
The tertiary structure of destrin was determined by the use of triple-resonance multidimensional nuclear magnetic resonance, NMR.[1] The secondary and tertiary structures of destrin are similar to the gelsolin family which is another actin-regulating protein family.
There are three ordered layers to destrin which is a globular protein. There is a central β sheet that is composed of one parallel strand and three antiparallel strands. This β sheet is between a long α helix along with a shorter one and two shorter helices on the opposite side. The four helices are parallel to the β strands.[1]
# Function
In a variety of eukaryotes, destrin regulates actin in the cytoskeleton. Destrin binds actin and is thought to connect it as gelsolin segment-1 does. Furthermore, the binding of actin by destrin and cofilin is regulated negatively by phosphorylation. Destrin can also sever actin filaments.[1] | https://www.wikidoc.org/index.php/Destrin | |
d244f3f1a5693b0c3720f80e286ff1cfc5752bce | wikidoc | Hydrate | Hydrate
# Overview
Hydrate is a term used in inorganic chemistry and organic chemistry to indicate that a substance contains water. The chemical state of the water varies widely between hydrates, some of which were so labeled before their chemical structure was understood.
In organic chemistry, a hydrate is a compound formed by the addition of water or its elements to a host molecule. For example, ethanol, CH3—CH2—OH, can be considered as a hydrate of ethylene, CH2=CH2, formed by the addition of H to one C and OH to the other C. A molecule of water may be eliminated, for example by the action of sulphuric acid. Another example is chloral hydrate, CCl3—CH(OH)2, which can be formed by reaction of water with chloral, CCl3—CH=O.
Other molecules have been labeled as hydrates for historical reasons. Glucose, C6H12O6, was originally thought of as C6(H2O)6 and described as a carbohydrate, but this is a very poor description of its structure as known today. And methanol is often sold as “methyl hydrate”, implying an incorrect formula CH3OH2, although the correct formula is CH3—OH.
In inorganic chemistry, hydrates contain water molecules that are either bound to a metal center or crystallized with the metal complex. Such hydrates are also said to contain "water of crystallization" or "water of hydration". If the water is heavy water, where the hydrogen consists of the isotope deuterium, then the term deuterate may be used in place of hydrate.
A colorful example is cobalt(II) chloride, which turns from blue to magenta (red) upon hydration, and can therefore be used as a water indicator.
The notation of hydrous compoundTemplate:Hydrate, where n is the number of water molecules per molecule of salt, is commonly used to show that a salt is hydrated. The n is usually a low integer, though it is possible for fractional values to exist. In a monohydrate n is one, in a hexahydrate n is 6 etc. Such water is also referred to as water of crystallization. Examples include borax decahydrate, clathrate hydrates (a class of solid hydrates of gases), and chalcanthite. Gas hydrates are clathrate hydrates: water ice with gas molecules trapped within. When the gas is methane it is called a methane hydrate.
A substance which has lost water is referred to as an anhydride, and can normally lose further water only upon strong heating, if at all. A substance which contains no water is referred to as anhydrous.
# Construction
The presence of hydrates is quite purposeful in the three fields of endeavour. Generally, in construction and refractories, inorganic binders are often deprived of water during manufacture. For instance, both in cement and gypsum products, heat is applied to the raw materials. Once water is added on a construction site, the powder is re-hydrated and able to form bonds with other substances that are present. Thus, one goes from powder, to slurry, or paste and then forms "cement stone". Water that is not chemically bound, or converted into hydrates, can come off again as steam, especially due to the heat of hydration, with cement products in particular, which undergo an exothermic chemical reaction with water.
Generally, the longer one can keep cementitious products wet immediately after placement, the better. The wetter cementitious products are kept, the more water will be converted into hydrates, instead of evaporating off due to the heat of hydration and other environmental influences. Premature drying is a cause for severe concrete problems, such as cracking and shrinking.
# Passive fire protection
Avoiding premature drying is important to all other cementitious building products, such as spray fireproofing and firestop mortars in particular, where the slightest cracking can lead to rejections. The chemically bound water, is the source for endothermic reactions when exposed to fire. Fire temperatures in a building can reach 1100°C, depending on the fuel present and the availability of oxygen. The presence of hydrates keep the item exposed to the heat at or below 100 °C, until all the water is spent. Therefore, the more hydrates, the longer the fire-resistance duration. This is what lends fire-resistive characteristics to basic, or "old" building materials, like gypsum, concrete or plaster.
# Space physics
Fire-resistance duration is important to many high-tech PFP products such as intumescent and endothermic paints, wraps and tiles, such as those used in space physics, for re-entry vehicles. | Hydrate
# Overview
Hydrate is a term used in inorganic chemistry and organic chemistry to indicate that a substance contains water. The chemical state of the water varies widely between hydrates, some of which were so labeled before their chemical structure was understood.
In organic chemistry, a hydrate is a compound formed by the addition of water or its elements to a host molecule. For example, ethanol, CH3—CH2—OH, can be considered as a hydrate of ethylene, CH2=CH2, formed by the addition of H to one C and OH to the other C. A molecule of water may be eliminated, for example by the action of sulphuric acid. Another example is chloral hydrate, CCl3—CH(OH)2, which can be formed by reaction of water with chloral, CCl3—CH=O.
Other molecules have been labeled as hydrates for historical reasons. Glucose, C6H12O6, was originally thought of as C6(H2O)6 and described as a carbohydrate, but this is a very poor description of its structure as known today. And methanol is often sold as “methyl hydrate”, implying an incorrect formula CH3OH2, although the correct formula is CH3—OH.
In inorganic chemistry, hydrates contain water molecules that are either bound to a metal center or crystallized with the metal complex. Such hydrates are also said to contain "water of crystallization" or "water of hydration". If the water is heavy water, where the hydrogen consists of the isotope deuterium, then the term deuterate may be used in place of hydrate.
A colorful example is cobalt(II) chloride, which turns from blue to magenta (red) upon hydration, and can therefore be used as a water indicator.
The notation of hydrous compoundTemplate:Hydrate, where n is the number of water molecules per molecule of salt, is commonly used to show that a salt is hydrated. The n is usually a low integer, though it is possible for fractional values to exist. In a monohydrate n is one, in a hexahydrate n is 6 etc. Such water is also referred to as water of crystallization. Examples include borax decahydrate, clathrate hydrates (a class of solid hydrates of gases), and chalcanthite. Gas hydrates are clathrate hydrates: water ice with gas molecules trapped within. When the gas is methane it is called a methane hydrate.
A substance which has lost water is referred to as an anhydride, and can normally lose further water only upon strong heating, if at all. A substance which contains no water is referred to as anhydrous.
# Construction
The presence of hydrates is quite purposeful in the three fields of endeavour. Generally, in construction and refractories, inorganic binders are often deprived of water during manufacture. For instance, both in cement and gypsum products, heat is applied to the raw materials. Once water is added on a construction site, the powder is re-hydrated and able to form bonds with other substances that are present. Thus, one goes from powder, to slurry, or paste and then forms "cement stone". Water that is not chemically bound, or converted into hydrates, can come off again as steam, especially due to the heat of hydration, with cement products in particular, which undergo an exothermic chemical reaction with water.
Generally, the longer one can keep cementitious products wet immediately after placement, the better. The wetter cementitious products are kept, the more water will be converted into hydrates, instead of evaporating off due to the heat of hydration and other environmental influences. Premature drying is a cause for severe concrete problems, such as cracking and shrinking.
# Passive fire protection
Avoiding premature drying is important to all other cementitious building products, such as spray fireproofing and firestop mortars in particular, where the slightest cracking can lead to rejections. The chemically bound water, is the source for endothermic reactions when exposed to fire. Fire temperatures in a building can reach 1100°C, depending on the fuel present and the availability of oxygen. The presence of hydrates keep the item exposed to the heat at or below 100 °C, until all the water is spent. Therefore, the more hydrates, the longer the fire-resistance duration. This is what lends fire-resistive characteristics to basic, or "old" building materials, like gypsum, concrete or plaster.
# Space physics
Fire-resistance duration is important to many high-tech PFP products such as intumescent and endothermic paints, wraps and tiles, such as those used in space physics, for re-entry vehicles. | https://www.wikidoc.org/index.php/Deuterate | |
696a90ea705bf5bc5b6b09d593b55f1965300eec | wikidoc | Dextran | Dextran
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Dextran is a volume expander that is FDA approved for the treatment of shock or impending shock,venous thrombosis, pulmonary embolism. Common adverse reactions include anaphylactoid reaction, generalized urticaria, tightness of the chest, wheezing, hypotension, nausea and vomiting.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
# Indications
- Dextran 40 is indicated for use in the adjunctive treatment of shock or impending shock due to hemorrhage, burns, surgery or other trauma. It is not indicated as a replacement for whole blood or blood components if they are available. It should not replace other forms of therapy known to be of value in the treatment of shock.
- Dextran 40 is also indicated for use as a priming fluid, either as a sole prime or as an additive, in pump oxygenators during extracorporeal circulation.
- Dextran 40 is also indicated for use in prophylaxis of venous thrombosis and pulmonary embolism in patients undergoing procedures known to be associated with a high incidence of thromboembolic complications, such as hip surgery.
# Dosage
Dextran 1 should be administered prior to administration of clinical dextran solutions.
- In shock, it is suggested that total dosage not exceed 20 mL/kg for adults and adolescents, during the first 24 hours. The first 10 mL/kg may be infused as rapidly as necessary to effect improvement. It is strongly recommended that central venous pressure be monitored frequently during the initial infusion of the drug. Should therapy continue beyond 24 hours, subsequent dosage should not exceed 10 mL/kg per day and therapy should not continue beyond five days.
- In extracorporeal perfusion, the dosage of LMD used will vary with the volume of the pump oxygenator. LMD can serve as a sole primer or as an additive to other priming fluids. For adults and adolescents, generally 10 to 20 mL of a 10% solution (1 to 2 g) of LMD per kilogram of body weight are added to the perfusion circuit. Usually total dosage should not exceed 2 g/kg of body weight.
- In prophylaxis of venous thrombosis and thromboembolism, the dosage of LMD for adults and adolescents, should be chosen according to the risk of thromboembolic complications, e.g., type of surgery and duration of immobilization. In general, treatment should be initiated during surgery; 500 to 1000 mL (approximately 10 mL/kg of body weight) should be administered on the day of operation. Treatment should be continued at a dose of 500 mL daily for an additional two to three days; then, according to the risk of complications, 500 mL may be given every second or third day during the period of risk, for up to two weeks.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Dextran in adult patients.
### Non–Guideline-Supported Use
# Indication
Transplant of lung, Lung preservation
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
# Indications
- Dextran 40 is indicated for use in the adjunctive treatment of shock or impending shock due to hemorrhage, burns, surgery or other trauma. It is not indicated as a replacement for whole blood or blood components if they are available. It should not replace other forms of therapy known to be of value in the treatment of shock.
- Dextran 40 is also indicated for use as a priming fluid, either as a sole prime or as an additive, in pump oxygenators during extracorporeal circulation.
- Dextran 40 is also indicated for use in prophylaxis of venous thrombosis and pulmonary embolism in patients undergoing procedures known to be associated with a high incidence of thromboembolic complications, such as hip surgery.
# Dosing
- In shock, it is suggested that total dosage not exceed 20 mL/kg for adults and adolescents, during the first 24 hours. The first 10 mL/kg may be infused as rapidly as necessary to effect improvement. It is strongly recommended that central venous pressure be monitored frequently during the initial infusion of the drug. Should therapy continue beyond 24 hours, subsequent dosage should not exceed 10 mL/kg per day and therapy should not continue beyond five days.
- In extracorporeal perfusion, the dosage of LMD used will vary with the volume of the pump oxygenator. LMD can serve as a sole primer or as an additive to other priming fluids. For adults and adolescents, generally 10 to 20 mL of a 10% solution (1 to 2 g) of LMD per kilogram of body weight are added to the perfusion circuit. Usually total dosage should not exceed 2 g/kg of body weight.
- In prophylaxis of venous thrombosis and thromboembolism, the dosage of LMD for adults and adolescents, should be chosen according to the risk of thromboembolic complications, e.g., type of surgery and duration of immobilization. In general, treatment should be initiated during surgery; 500 to 1000 mL (approximately 10 mL/kg of body weight) should be administered on the day of operation. Treatment should be continued at a dose of 500 mL daily for an additional two to three days; then, according to the risk of complications, 500 mL may be given every second or third day during the period of risk, for up to two weeks.
- Infants may be given 5 mL per kg body weight and children 10 mL per kg.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Dextran in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Dextran in pediatric patients.
# Contraindications
- LMD (dextran 40) is contraindicated in patients with known hypersensitivity to dextran, in those with marked hemostatic defects of all types (thrombocytopenia, hypofibrinogenemia, etc.) including those caused by drugs (heparin, warfarin, etc.), marked cardiac decompensation and in renal disease with severe oliguria or anuria.
# Warnings
Although infrequent, severe and fatal anaphylactoid reactions consisting of marked hypotension or cardiac and respiratory arrest have been reported, most of these reactions have occurred in patients not previously exposed to intravenous dextran and early in the infusion period. It is strongly recommended, therefore, that patients not previously exposed to dextran be observed closely during the first minutes of the infusion period.
Anaphylactoid Reactions
- There have been rare reports of serious and life-threatening dextran-induced anaphylactoid reactions (DIAR) associated with Dextran 40 and Dextran 70 administration. To reduce the likelihood of DIAR, 20 mL dextran 1 should be administered prior to infusion of Dextran 40 or Dextran 70 consistent with the dextran 1 package insert.1-5 . Investigators have reported a 35-fold decrease (from 1:2000 to 1:70,000) in the incidence of DIAR following prophylactic use of dextran 1.6 However, serious and life-threatening reactions may still occur following initiation of an infusion of any clinical dextran.
- Because of the seriousness of anaphylactoid reactions, it is recommended that the infusion of intravenous dextran be stopped at the first sign of an allergic reaction provided that other means of sustaining the circulation are available. Resuscitative measures should be readily available for emergency administration in the event such a reaction occurs. In circulatory collapse due to anaphylaxis, rapid volume substitutions with an agent other than dextran should be instituted.
- Because dextran 40 is a hypertonic colloid solution, it attracts water from the extravascular space. This shift of fluid should be considered if the drug is used for poorly hydrated patients where additional fluid therapy will be needed. If dextran 40 is given in excess, vascular overload could occur. The latter possibility can be avoided with careful clinical monitoring preferably by central venous pressure.
- Renal excretion of dextran 40 causes elevations of the specific gravity of the urine. In the presence of adequate urine flow only minor elevation will occur, whereas in patients with reduced urine output, urine viscosity and specific gravity can be increased markedly. Since urine osmolarity is only slightly increased by the presence of dextran molecules, it is recommended that, when desired, a patient’s state of hydration be assessed by determination of urine or serum osmolarity. If signs of dehydration are present, additional fluid should be administered. An osmotic diuretic such as mannitol also can be used to maintain an adequate urine flow.
- Although numerous studies attest to the “nephrotonic” effect of LMD, renal failure has been reported to occur after the use of dextran 40.
- Evidence of tubular vacuolization (osmotic nephrosis) has been found following dextran 40 administration in animals and man. While this appears to be reversible experimentally in animals and to be a consequence of high urine concentration of the drug, its exact clinical significance is presently unknown.
- Occasional abnormal renal and hepatic function values have been reported following administration of dextran 40. However, the specific effect of dextran 40 on renal and hepatic function could not be determined because most of the patients also had undergone surgery or cardiac catheterization. A comparative study of dextran 40 and 5% dextrose in water as pump-priming fluids in open-heart surgery has shown similar elevations of serum glutamic oxaloacetic transaminase (SGOT), aspartate aminotransferase and serum glutamic pyruvic transaminase (SGPT), alanine aminotransferase values in both groups.
- Caution should be employed when LMD is administered to patients with active hemorrhage as the resulting increase in perfusion pressure and improved microcirculatory flow may result in additional blood loss.
- Administering infusions of dextran 40 that exceed the recommended dose should be avoided, since a dose-related increase in the incidence of wound hematoma, wound seroma, wound bleeding, distant bleeding (hematuria and melena) and pulmonary edema has been observed. Recommended doses should never be exceeded in patients with advanced renal disease, since excessive doses may precipitate renal failure.
- Dextran may interfere to some extent with platelet function and should be used with caution in cases with thrombocytopenia. Transient prolongation of bleeding time and/or slightly increased bleeding tendency may occur with the administration of doses greater than 1000 mL. Care should be taken to prevent a depression of hematocrit below 30% by volume. When large volumes of dextran are administered, plasma protein levels will be decreased.
- Solutions containing sodium ions should be used with great care, if at all, in patients with congestive heart failure, severe renal insufficiency and in clinical states in which there exists edema with sodium retention.
- The intravenous administration of this solution can cause fluid and/or solute overloading resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentrations of administered parenteral solutions.
- The risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the electrolyte concentrations of such solutions.
- In patients with diminished renal function, administration of solutions containing sodium ions may result in sodium retention.
PRECAUTIONS
- The possibility of circulatory overload should be kept in mind. Special care should be exercised in patients with impaired renal clearance of dextran. When the risk of pulmonary edema and/or congestive heart failure may be increased, dextran should be used with caution.
- In patients with normal hemostasis, dosage of dextran 40 approximating 15 mL/kg of body weight may prolong bleeding time and depress platelet function. Dosages in this range also markedly decrease factor VIII, and decrease factors V and IX to a greater degree than would be expected to occur from hemodilution alone. Since these changes tend to be more pronounced following trauma or major surgery, patients should be observed for early signs of bleeding complications.
- Since increased rouleaux formation may occur in the presence of dextran, it is recommended that blood samples be drawn for typing and cross-matching prior to the infusion of dextran and reserved for subsequent use if necessary. If blood is drawn after infusion of dextran, the saline agglutination and indirect antiglobulin methods may be used for typing and cross-matching. Difficulty may be encountered when proteolytic enzyme techniques are used to match blood.
- Consideration should be given to withdrawal of blood for chemical laboratory tests prior to initiating therapy with dextran because of the following:
- Blood sugar determinations that employ high concentrations of acid may result in hydrolysis of dextran, yielding falsely elevated glucose assay results. This has been observed both with sulfuric acid and with acetic acid.
- In other laboratory tests, the presence of dextran in the blood may result in the development of turbidity, which can interfere with the assay. This has been observed in bilirubin assays in which alcohol is employed and in total protein assays employing biuret reagent.
- Solutions containing dextrose should be used with caution in patients with known subclinical or overt diabetes mellitus.
- Caution must be exercised in the administration of parenteral fluids, especially those containing sodium ions, to patients receiving corticosteroids or corticotropin.
- Do not administer unless solution is clear and container is undamaged. Discard unused portion.
# Adverse Reactions
## Clinical Trials Experience
- Antigenicity of dextrans is directly related to their degree of branching. Since dextran 40 has a low degree of branching, it is relatively free of antigenic effect. However, a few individuals have experienced mild urticarial reactions. More severe reactions, consisting of severe anaphylactoid reaction, generalized urticaria, tightness of the chest, wheezing, hypotension, nausea and vomiting may occur in rare instances. Symptoms and signs of adverse systemic reaction may be relieved by parenteral administration of antihistamines, ephedrine or epinephrine, while other means of shock therapy are instituted. The route of administration and dosages of the therapeutic agent selected will depend upon the severity and rapidity of progression of the reaction.
- Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia.
- If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures, and save the remainder of the fluid for examination if deemed necessary.
## Postmarketing Experience
Severe reactions have been observed with Dextran 40 and Dextran 70. Reported reactions include: generalized urticaria, nausea and vomiting, wheezing, hypotension, shock and cardiac arrest (dextran-induced anaphylactoid reactions, DIAR). FDA has received 94 reports of severe DIAR since 1964. Because these reactions are reported voluntarily and the treated population is of indeterminate size, the frequency of reactions cannot be estimated reliably.
# Drug Interactions
- Additive medications should not be delivered via plasma volume expanders.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
Pregnancy Category C
- Animal reproduction studies have not been conducted with dextran 40 in dextrose or sodium chloride. It is also not known whether dextran 40 in dextrose or sodium chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. 10% LMD (dextran 40) in dextrose or sodium chloride should be given to a pregnant woman only if clearly needed.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Dextran in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Dextran during labor and delivery.
### Nursing Mothers
- It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when 10% LMD (dextran 40) in dextrose or sodium chloride is administered to a nursing woman.
### Pediatric Use
The safety and effectiveness of dextran 40 have not been established in neonates. Its limited use in neonates has been inadequate to fully define proper dosage and limitations for use.
### Geriatic Use
There is no FDA guidance on the use of Dextran with respect to geriatric patients.
### Gender
There is no FDA guidance on the use of Dextran with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Dextran with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Dextran in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Dextran in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Dextran in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Dextran in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Intravenous
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
- Note: When infusing concentrated LMD, the administration set should include a filter.
Preparation for Administration
(Use aseptic technique)
- Close flow control clamp of administration set.
- Remove cover from outlet port at bottom of container.
- Insert piercing pin of administration set into port with a twisting motion until the set is firmly seated. Note: See full directions on administration set carton.
- Suspend container from hanger.
- Squeeze and release drip chamber to establish proper fluid level in drip chamber.
- Open flow control clamp and clear air from set. Close clamp.
- Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture.
- Regulate rate of administration with flow control clamp.
WARNING: Do not use flexible container in series connections.
### Monitoring
There is limited information regarding Monitoring of Dextran in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Dextran in the drug label.
# Overdosage
There is limited information regarding Dextran overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
# Pharmacology
## Mechanism of Action
The fundamental action of dextran 40 is the enhancement of blood flow, particularly in the microcirculation. This enhancement is due to:
- Its primary effect of volume expansion with resultant hemodilution;
- Maintenance of the electronegativity of red blood cells;
- Coating of red blood cells and platelets;
- Increase in the suspension stability of blood;
- Decrease in the viscosity of blood.
- It should be emphasized that the above effects are not exerted separately, but conjointly they result in the enhancement of blood flow.
- Dextran 40, used in the treatment of shock, produces significant increases in blood volume, central venous pressure, cardiac output, stroke volume, blood pressure and urinary output. It reduces blood viscosity, peripheral resistance and improves peripheral blood flow with the release of sequestered blood cells, thereby increasing venous return to the heart.
- When used as part of the pump prime for extracorporeal procedures, dextran 40, as compared to whole blood, albumin 5%, or whole blood plus 5% dextrose and water, leads to less destruction of red blood cells and platelets, reduces intravascular hemagglutination and maintains erythrocyte electronegativity.
- The infusion of dextran 40 during and after surgical trauma reduces the incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients subject to surgical procedures with a high incidence of thromboembolic complication. Unlike antithrombogenic agents of the anticoagulant type, dextran 40 does not achieve its effect so much by blocking fibrinogen-fibrin conversion but acts by simultaneously inhibiting other mechanisms essential to thrombus formation such as vascular stasis and platelet adhesiveness and by altering the structure and thereby the lysability of fibrin clots.
- Histopathological studies have shown that the development of a mural platelet thrombus is the first stage of thrombus formation not only in the arterial, but also in the venous system. A number of studies have further shown that many patients who develop thromboembolic complications show an abnormally high platelet adhesiveness. Infusion of LMD has been shown to reduce platelet adhesiveness as measured by various in vitro tests on blood samples obtained from humans and to inhibit the growth of a mural platelet thrombus at the site of experimental (laser beam) injury in the rabbit’s ear chamber.
- Studies have shown an increase in the lysability of thrombi formed in the presence of dextran. A consistent and characteristic alteration in fibrin structure has been observed when fibrin is formed in the presence of dextran, and further experiments demonstrated such fibrin to be more susceptible to plasmin digestion. Other studies have shown that dextran infused into patients during surgery increases the lysability of ex vivo thrombi. Controlled clinical trials have shown that thrombi in patients treated with dextran have a more pronounced tendency to undergo lysis as determined by phlebography.
- Dextran 40 is evenly distributed in the vascular system. Its distribution according to molecular weight shifts toward higher molecular weights as the smaller molecules are excreted by the kidney. In normovolemic subjects, approximately 50% is excreted within 3 hours, 60% is excreted within 6 hours and about 75% within 24 hours. Reabsorption of dextran by the renal tubules is negligible. The unexcreted molecules of dextran diffuse into the extravascular compartment and are temporarily taken up by the reticuloendothelial system. Some of these molecules are returned to the intravascular compartment via the lymphatics. Dextran is slowly degraded by the enzyme dextranase to glucose.
- Solutions containing carbohydrate in the form of dextrose restore blood glucose levels and provide calories. Carbohydrate in the form of dextrose may aid in minimizing liver glycogen depletion and exerts a protein sparing action. Dextrose injected parenterally undergoes oxidation to carbon dioxide and water.
- Sodium chloride in water dissociates to provide sodium (Na+) and chloride (Cl¯) ions. Sodium (Na+) is the principal cation of the extracellular fluid and plays a large part in the therapy of fluid and electrolyte disturbances. Chloride (Cl¯) has an integral role in buffering action when oxygen and carbon dioxide exchange occurs in red blood cells. The distribution and excretion of sodium (Na+) and chloride (Cl¯) are largely under the control of the kidney, which maintains a balance between intake and output.
- Water is an essential constituent of all body tissues and accounts for approximately 70% of total body weight. Average normal adult daily requirement ranges from two to three liters (1.0 to 1.5 liters each for insensible water loss by perspiration and urine production).
- Water balance is maintained by various regulatory mechanisms. Water distribution depends primarily on the concentration of electrolytes in the body compartments and sodium (Na+) plays a major role in maintaining physiologic equilibrium.
## Structure
- LMD (dextran 40) is a sterile, nonpyrogenic preparation of low molecular weight dextran (average mol. wt. 40,000) in 5% Dextrose Injection or 0.9% Sodium Chloride Injection. It is administered by intravenous infusion.
- Also described as low viscous or low viscosity dextran, dextran 40 is prepared by acid hydrolysis and differential fractionation of a crude macromolecular polysaccharide produced from the fermentation of sucrose by the bacterium, Leuconostoc mesenteroides (strain B-512). The crude material is composed of linked glucose units. In the fraction represented by dextran 40, 80% of the molecules have a molecular weight ranging from 10,000 to 90,000 (average approximately 40,000) when measured by a light scattering method. More than 90% of the linkages are of the 1,6 alpha glucosidic, straight chain type.
- Each 100 mL of 10% LMD (dextran 40) in 5% Dextrose Injection contains 10 g dextran 40 and 5 g dextrose hydrous in water for injection. Total osmolar concentration is 255 mOsmol/liter (calc.); pH is 4.4 (3.0 to 7.0).
- Each 100 mL of 10% LMD (dextran 40) in 0.9% Sodium Chloride Injection contains 10 g dextran 40 and 0.9 g sodium chloride in water for injection. Total osmolar concentration is 310 mOsmol/liter (calc.); pH is 4.9 (3.5 to 7.0) (may contain sodium hydroxide and/or hydrochloric acid for pH adjustment). Electrolyte concentration per liter: Na+ 154 mEq; Cl¯ 154 mEq (not including ions for pH adjustment).
- The solutions contain no bacteriostat, antimicrobial agent or added buffers (except for pH adjustment) and are intended only for single-dose injection. When smaller doses are required the unused portion should be discarded.
- 10% LMD (dextran 40) is an artificial colloid pharmacologically classified as a plasma volume expander; 5% Dextrose Injection is a fluid and nutrient replenisher; 0.9% Sodium Chloride Injection is a fluid and electrolyte replenisher.
- Dextran 40 is a linear glucose polymer (polysaccharide) chemically designated (C6 H10 O5)n.
- The structural formula for dextran (repeating unit) is:
- Dextrose, USP is chemically designated D-glucose monohydrate(C6 H12 O6 - H2O), a hexose sugar freely soluble in water.
- Sodium Chloride, USP is chemically designated NaCl, a white crystalline powder freely soluble in water.
- Water for Injection, USP is chemically designated H2O.
- The flexible plastic container is fabricated from a specially formulated polyvinylchloride. Water can permeate from inside the container into the overwrap but not in amounts sufficient to affect the solution significantly. Solutions inside the plastic container also can leach out certain of the chemical components of the plastic in very small amounts before the expiration period is attained. However, safety of the plastic has been confirmed by tests in animals according to USP biological standards for plastic containers.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Dextran in the drug label.
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Dextran in the drug label.
## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Dextran in the drug label.
# Clinical Studies
There is limited information regarding Clinical Studies of Dextran in the drug label.
# How Supplied
- 10% dextran 40 in 5% Dextrose Injection (Dextran 40 in Dextrose Injection, USP) is supplied in a 500 mL single-dose flexible container (NDC 0409-7418-03). 10% LMD in 0.9% Sodium Chloride Injection (Dextran 40 in Sodium Chloride Injection, USP) is supplied in a 500 mL single-dose flexible container (NDC 0409-7419-03).
## Storage
- Store at 20 to 25°C (68 to 77°F). Protect from freezing.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Dextran in the drug label.
# Precautions with Alcohol
- Alcohol-Dextran interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- LMD IN DEXTROSE
- LMD IN SODIUM CHLORIDE
# Look-Alike Drug Names
There is limited information regarding Dextran Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Dextran
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]
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# Overview
Dextran is a volume expander that is FDA approved for the treatment of shock or impending shock,venous thrombosis, pulmonary embolism. Common adverse reactions include anaphylactoid reaction, generalized urticaria, tightness of the chest, wheezing, hypotension, nausea and vomiting.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
# Indications
- Dextran 40 is indicated for use in the adjunctive treatment of shock or impending shock due to hemorrhage, burns, surgery or other trauma. It is not indicated as a replacement for whole blood or blood components if they are available. It should not replace other forms of therapy known to be of value in the treatment of shock.
- Dextran 40 is also indicated for use as a priming fluid, either as a sole prime or as an additive, in pump oxygenators during extracorporeal circulation.
- Dextran 40 is also indicated for use in prophylaxis of venous thrombosis and pulmonary embolism in patients undergoing procedures known to be associated with a high incidence of thromboembolic complications, such as hip surgery.
# Dosage
Dextran 1 should be administered prior to administration of clinical dextran solutions.
- In shock, it is suggested that total dosage not exceed 20 mL/kg for adults and adolescents, during the first 24 hours. The first 10 mL/kg may be infused as rapidly as necessary to effect improvement. It is strongly recommended that central venous pressure be monitored frequently during the initial infusion of the drug. Should therapy continue beyond 24 hours, subsequent dosage should not exceed 10 mL/kg per day and therapy should not continue beyond five days.
- In extracorporeal perfusion, the dosage of LMD used will vary with the volume of the pump oxygenator. LMD can serve as a sole primer or as an additive to other priming fluids. For adults and adolescents, generally 10 to 20 mL of a 10% solution (1 to 2 g) of LMD per kilogram of body weight are added to the perfusion circuit. Usually total dosage should not exceed 2 g/kg of body weight.
- In prophylaxis of venous thrombosis and thromboembolism, the dosage of LMD for adults and adolescents, should be chosen according to the risk of thromboembolic complications, e.g., type of surgery and duration of immobilization. In general, treatment should be initiated during surgery; 500 to 1000 mL (approximately 10 mL/kg of body weight) should be administered on the day of operation. Treatment should be continued at a dose of 500 mL daily for an additional two to three days; then, according to the risk of complications, 500 mL may be given every second or third day during the period of risk, for up to two weeks.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Dextran in adult patients.
### Non–Guideline-Supported Use
# Indication
Transplant of lung, Lung preservation[1]
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
# Indications
- Dextran 40 is indicated for use in the adjunctive treatment of shock or impending shock due to hemorrhage, burns, surgery or other trauma. It is not indicated as a replacement for whole blood or blood components if they are available. It should not replace other forms of therapy known to be of value in the treatment of shock.
- Dextran 40 is also indicated for use as a priming fluid, either as a sole prime or as an additive, in pump oxygenators during extracorporeal circulation.
- Dextran 40 is also indicated for use in prophylaxis of venous thrombosis and pulmonary embolism in patients undergoing procedures known to be associated with a high incidence of thromboembolic complications, such as hip surgery.
# Dosing
- In shock, it is suggested that total dosage not exceed 20 mL/kg for adults and adolescents, during the first 24 hours. The first 10 mL/kg may be infused as rapidly as necessary to effect improvement. It is strongly recommended that central venous pressure be monitored frequently during the initial infusion of the drug. Should therapy continue beyond 24 hours, subsequent dosage should not exceed 10 mL/kg per day and therapy should not continue beyond five days.
- In extracorporeal perfusion, the dosage of LMD used will vary with the volume of the pump oxygenator. LMD can serve as a sole primer or as an additive to other priming fluids. For adults and adolescents, generally 10 to 20 mL of a 10% solution (1 to 2 g) of LMD per kilogram of body weight are added to the perfusion circuit. Usually total dosage should not exceed 2 g/kg of body weight.
- In prophylaxis of venous thrombosis and thromboembolism, the dosage of LMD for adults and adolescents, should be chosen according to the risk of thromboembolic complications, e.g., type of surgery and duration of immobilization. In general, treatment should be initiated during surgery; 500 to 1000 mL (approximately 10 mL/kg of body weight) should be administered on the day of operation. Treatment should be continued at a dose of 500 mL daily for an additional two to three days; then, according to the risk of complications, 500 mL may be given every second or third day during the period of risk, for up to two weeks.
- Infants may be given 5 mL per kg body weight and children 10 mL per kg.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Dextran in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Dextran in pediatric patients.
# Contraindications
- LMD (dextran 40) is contraindicated in patients with known hypersensitivity to dextran, in those with marked hemostatic defects of all types (thrombocytopenia, hypofibrinogenemia, etc.) including those caused by drugs (heparin, warfarin, etc.), marked cardiac decompensation and in renal disease with severe oliguria or anuria.
# Warnings
Although infrequent, severe and fatal anaphylactoid reactions consisting of marked hypotension or cardiac and respiratory arrest have been reported, most of these reactions have occurred in patients not previously exposed to intravenous dextran and early in the infusion period. It is strongly recommended, therefore, that patients not previously exposed to dextran be observed closely during the first minutes of the infusion period.
Anaphylactoid Reactions
- There have been rare reports of serious and life-threatening dextran-induced anaphylactoid reactions (DIAR) associated with Dextran 40 and Dextran 70 administration. To reduce the likelihood of DIAR, 20 mL dextran 1 should be administered prior to infusion of Dextran 40 or Dextran 70 consistent with the dextran 1 package insert.1-5 . Investigators have reported a 35-fold decrease (from 1:2000 to 1:70,000) in the incidence of DIAR following prophylactic use of dextran 1.6 However, serious and life-threatening reactions may still occur following initiation of an infusion of any clinical dextran.
- Because of the seriousness of anaphylactoid reactions, it is recommended that the infusion of intravenous dextran be stopped at the first sign of an allergic reaction provided that other means of sustaining the circulation are available. Resuscitative measures should be readily available for emergency administration in the event such a reaction occurs. In circulatory collapse due to anaphylaxis, rapid volume substitutions with an agent other than dextran should be instituted.
- Because dextran 40 is a hypertonic colloid solution, it attracts water from the extravascular space. This shift of fluid should be considered if the drug is used for poorly hydrated patients where additional fluid therapy will be needed. If dextran 40 is given in excess, vascular overload could occur. The latter possibility can be avoided with careful clinical monitoring preferably by central venous pressure.
- Renal excretion of dextran 40 causes elevations of the specific gravity of the urine. In the presence of adequate urine flow only minor elevation will occur, whereas in patients with reduced urine output, urine viscosity and specific gravity can be increased markedly. Since urine osmolarity is only slightly increased by the presence of dextran molecules, it is recommended that, when desired, a patient’s state of hydration be assessed by determination of urine or serum osmolarity. If signs of dehydration are present, additional fluid should be administered. An osmotic diuretic such as mannitol also can be used to maintain an adequate urine flow.
- Although numerous studies attest to the “nephrotonic” effect of LMD, renal failure has been reported to occur after the use of dextran 40.
- Evidence of tubular vacuolization (osmotic nephrosis) has been found following dextran 40 administration in animals and man. While this appears to be reversible experimentally in animals and to be a consequence of high urine concentration of the drug, its exact clinical significance is presently unknown.
- Occasional abnormal renal and hepatic function values have been reported following administration of dextran 40. However, the specific effect of dextran 40 on renal and hepatic function could not be determined because most of the patients also had undergone surgery or cardiac catheterization. A comparative study of dextran 40 and 5% dextrose in water as pump-priming fluids in open-heart surgery has shown similar elevations of serum glutamic oxaloacetic transaminase (SGOT), aspartate aminotransferase and serum glutamic pyruvic transaminase (SGPT), alanine aminotransferase values in both groups.
- Caution should be employed when LMD is administered to patients with active hemorrhage as the resulting increase in perfusion pressure and improved microcirculatory flow may result in additional blood loss.
- Administering infusions of dextran 40 that exceed the recommended dose should be avoided, since a dose-related increase in the incidence of wound hematoma, wound seroma, wound bleeding, distant bleeding (hematuria and melena) and pulmonary edema has been observed. Recommended doses should never be exceeded in patients with advanced renal disease, since excessive doses may precipitate renal failure.
- Dextran may interfere to some extent with platelet function and should be used with caution in cases with thrombocytopenia. Transient prolongation of bleeding time and/or slightly increased bleeding tendency may occur with the administration of doses greater than 1000 mL. Care should be taken to prevent a depression of hematocrit below 30% by volume. When large volumes of dextran are administered, plasma protein levels will be decreased.
- Solutions containing sodium ions should be used with great care, if at all, in patients with congestive heart failure, severe renal insufficiency and in clinical states in which there exists edema with sodium retention.
- The intravenous administration of this solution can cause fluid and/or solute overloading resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentrations of administered parenteral solutions.
- The risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the electrolyte concentrations of such solutions.
- In patients with diminished renal function, administration of solutions containing sodium ions may result in sodium retention.
PRECAUTIONS
- The possibility of circulatory overload should be kept in mind. Special care should be exercised in patients with impaired renal clearance of dextran. When the risk of pulmonary edema and/or congestive heart failure may be increased, dextran should be used with caution.
- In patients with normal hemostasis, dosage of dextran 40 approximating 15 mL/kg of body weight may prolong bleeding time and depress platelet function. Dosages in this range also markedly decrease factor VIII, and decrease factors V and IX to a greater degree than would be expected to occur from hemodilution alone. Since these changes tend to be more pronounced following trauma or major surgery, patients should be observed for early signs of bleeding complications.
- Since increased rouleaux formation may occur in the presence of dextran, it is recommended that blood samples be drawn for typing and cross-matching prior to the infusion of dextran and reserved for subsequent use if necessary. If blood is drawn after infusion of dextran, the saline agglutination and indirect antiglobulin methods may be used for typing and cross-matching. Difficulty may be encountered when proteolytic enzyme techniques are used to match blood.
- Consideration should be given to withdrawal of blood for chemical laboratory tests prior to initiating therapy with dextran because of the following:
- Blood sugar determinations that employ high concentrations of acid may result in hydrolysis of dextran, yielding falsely elevated glucose assay results. This has been observed both with sulfuric acid and with acetic acid.
- In other laboratory tests, the presence of dextran in the blood may result in the development of turbidity, which can interfere with the assay. This has been observed in bilirubin assays in which alcohol is employed and in total protein assays employing biuret reagent.
- Solutions containing dextrose should be used with caution in patients with known subclinical or overt diabetes mellitus.
- Caution must be exercised in the administration of parenteral fluids, especially those containing sodium ions, to patients receiving corticosteroids or corticotropin.
- Do not administer unless solution is clear and container is undamaged. Discard unused portion.
# Adverse Reactions
## Clinical Trials Experience
- Antigenicity of dextrans is directly related to their degree of branching. Since dextran 40 has a low degree of branching, it is relatively free of antigenic effect. However, a few individuals have experienced mild urticarial reactions. More severe reactions, consisting of severe anaphylactoid reaction, generalized urticaria, tightness of the chest, wheezing, hypotension, nausea and vomiting may occur in rare instances. Symptoms and signs of adverse systemic reaction may be relieved by parenteral administration of antihistamines, ephedrine or epinephrine, while other means of shock therapy are instituted. The route of administration and dosages of the therapeutic agent selected will depend upon the severity and rapidity of progression of the reaction.
- Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia.
- If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures, and save the remainder of the fluid for examination if deemed necessary.
## Postmarketing Experience
Severe reactions have been observed with Dextran 40 and Dextran 70. Reported reactions include: generalized urticaria, nausea and vomiting, wheezing, hypotension, shock and cardiac arrest (dextran-induced anaphylactoid reactions, DIAR). FDA has received 94 reports of severe DIAR since 1964. Because these reactions are reported voluntarily and the treated population is of indeterminate size, the frequency of reactions cannot be estimated reliably.
# Drug Interactions
- Additive medications should not be delivered via plasma volume expanders.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
Pregnancy Category C
- Animal reproduction studies have not been conducted with dextran 40 in dextrose or sodium chloride. It is also not known whether dextran 40 in dextrose or sodium chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. 10% LMD (dextran 40) in dextrose or sodium chloride should be given to a pregnant woman only if clearly needed.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Dextran in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Dextran during labor and delivery.
### Nursing Mothers
- It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when 10% LMD (dextran 40) in dextrose or sodium chloride is administered to a nursing woman.
### Pediatric Use
The safety and effectiveness of dextran 40 have not been established in neonates. Its limited use in neonates has been inadequate to fully define proper dosage and limitations for use.
### Geriatic Use
There is no FDA guidance on the use of Dextran with respect to geriatric patients.
### Gender
There is no FDA guidance on the use of Dextran with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Dextran with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Dextran in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Dextran in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Dextran in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Dextran in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Intravenous
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
- Note: When infusing concentrated LMD, the administration set should include a filter.
Preparation for Administration
(Use aseptic technique)
- Close flow control clamp of administration set.
- Remove cover from outlet port at bottom of container.
- Insert piercing pin of administration set into port with a twisting motion until the set is firmly seated. Note: See full directions on administration set carton.
- Suspend container from hanger.
- Squeeze and release drip chamber to establish proper fluid level in drip chamber.
- Open flow control clamp and clear air from set. Close clamp.
- Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture.
- Regulate rate of administration with flow control clamp.
WARNING: Do not use flexible container in series connections.
### Monitoring
There is limited information regarding Monitoring of Dextran in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Dextran in the drug label.
# Overdosage
There is limited information regarding Dextran overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
# Pharmacology
## Mechanism of Action
The fundamental action of dextran 40 is the enhancement of blood flow, particularly in the microcirculation. This enhancement is due to:
- Its primary effect of volume expansion with resultant hemodilution;
- Maintenance of the electronegativity of red blood cells;
- Coating of red blood cells and platelets;
- Increase in the suspension stability of blood;
- Decrease in the viscosity of blood.
- It should be emphasized that the above effects are not exerted separately, but conjointly they result in the enhancement of blood flow.
- Dextran 40, used in the treatment of shock, produces significant increases in blood volume, central venous pressure, cardiac output, stroke volume, blood pressure and urinary output. It reduces blood viscosity, peripheral resistance and improves peripheral blood flow with the release of sequestered blood cells, thereby increasing venous return to the heart.
- When used as part of the pump prime for extracorporeal procedures, dextran 40, as compared to whole blood, albumin 5%, or whole blood plus 5% dextrose and water, leads to less destruction of red blood cells and platelets, reduces intravascular hemagglutination and maintains erythrocyte electronegativity.
- The infusion of dextran 40 during and after surgical trauma reduces the incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients subject to surgical procedures with a high incidence of thromboembolic complication. Unlike antithrombogenic agents of the anticoagulant type, dextran 40 does not achieve its effect so much by blocking fibrinogen-fibrin conversion but acts by simultaneously inhibiting other mechanisms essential to thrombus formation such as vascular stasis and platelet adhesiveness and by altering the structure and thereby the lysability of fibrin clots.
- Histopathological studies have shown that the development of a mural platelet thrombus is the first stage of thrombus formation not only in the arterial, but also in the venous system. A number of studies have further shown that many patients who develop thromboembolic complications show an abnormally high platelet adhesiveness. Infusion of LMD has been shown to reduce platelet adhesiveness as measured by various in vitro tests on blood samples obtained from humans and to inhibit the growth of a mural platelet thrombus at the site of experimental (laser beam) injury in the rabbit’s ear chamber.
- Studies have shown an increase in the lysability of thrombi formed in the presence of dextran. A consistent and characteristic alteration in fibrin structure has been observed when fibrin is formed in the presence of dextran, and further experiments demonstrated such fibrin to be more susceptible to plasmin digestion. Other studies have shown that dextran infused into patients during surgery increases the lysability of ex vivo thrombi. Controlled clinical trials have shown that thrombi in patients treated with dextran have a more pronounced tendency to undergo lysis as determined by phlebography.
- Dextran 40 is evenly distributed in the vascular system. Its distribution according to molecular weight shifts toward higher molecular weights as the smaller molecules are excreted by the kidney. In normovolemic subjects, approximately 50% is excreted within 3 hours, 60% is excreted within 6 hours and about 75% within 24 hours. Reabsorption of dextran by the renal tubules is negligible. The unexcreted molecules of dextran diffuse into the extravascular compartment and are temporarily taken up by the reticuloendothelial system. Some of these molecules are returned to the intravascular compartment via the lymphatics. Dextran is slowly degraded by the enzyme dextranase to glucose.
- Solutions containing carbohydrate in the form of dextrose restore blood glucose levels and provide calories. Carbohydrate in the form of dextrose may aid in minimizing liver glycogen depletion and exerts a protein sparing action. Dextrose injected parenterally undergoes oxidation to carbon dioxide and water.
- Sodium chloride in water dissociates to provide sodium (Na+) and chloride (Cl¯) ions. Sodium (Na+) is the principal cation of the extracellular fluid and plays a large part in the therapy of fluid and electrolyte disturbances. Chloride (Cl¯) has an integral role in buffering action when oxygen and carbon dioxide exchange occurs in red blood cells. The distribution and excretion of sodium (Na+) and chloride (Cl¯) are largely under the control of the kidney, which maintains a balance between intake and output.
- Water is an essential constituent of all body tissues and accounts for approximately 70% of total body weight. Average normal adult daily requirement ranges from two to three liters (1.0 to 1.5 liters each for insensible water loss by perspiration and urine production).
- Water balance is maintained by various regulatory mechanisms. Water distribution depends primarily on the concentration of electrolytes in the body compartments and sodium (Na+) plays a major role in maintaining physiologic equilibrium.
## Structure
- LMD (dextran 40) is a sterile, nonpyrogenic preparation of low molecular weight dextran (average mol. wt. 40,000) in 5% Dextrose Injection or 0.9% Sodium Chloride Injection. It is administered by intravenous infusion.
- Also described as low viscous or low viscosity dextran, dextran 40 is prepared by acid hydrolysis and differential fractionation of a crude macromolecular polysaccharide produced from the fermentation of sucrose by the bacterium, Leuconostoc mesenteroides (strain B-512). The crude material is composed of linked glucose units. In the fraction represented by dextran 40, 80% of the molecules have a molecular weight ranging from 10,000 to 90,000 (average approximately 40,000) when measured by a light scattering method. More than 90% of the linkages are of the 1,6 alpha glucosidic, straight chain type.
- Each 100 mL of 10% LMD (dextran 40) in 5% Dextrose Injection contains 10 g dextran 40 and 5 g dextrose hydrous in water for injection. Total osmolar concentration is 255 mOsmol/liter (calc.); pH is 4.4 (3.0 to 7.0).
- Each 100 mL of 10% LMD (dextran 40) in 0.9% Sodium Chloride Injection contains 10 g dextran 40 and 0.9 g sodium chloride in water for injection. Total osmolar concentration is 310 mOsmol/liter (calc.); pH is 4.9 (3.5 to 7.0) (may contain sodium hydroxide and/or hydrochloric acid for pH adjustment). Electrolyte concentration per liter: Na+ 154 mEq; Cl¯ 154 mEq (not including ions for pH adjustment).
- The solutions contain no bacteriostat, antimicrobial agent or added buffers (except for pH adjustment) and are intended only for single-dose injection. When smaller doses are required the unused portion should be discarded.
- 10% LMD (dextran 40) is an artificial colloid pharmacologically classified as a plasma volume expander; 5% Dextrose Injection is a fluid and nutrient replenisher; 0.9% Sodium Chloride Injection is a fluid and electrolyte replenisher.
- Dextran 40 is a linear glucose polymer (polysaccharide) chemically designated (C6 H10 O5)n.
- The structural formula for dextran (repeating unit) is:
- Dextrose, USP is chemically designated D-glucose monohydrate(C6 H12 O6 • H2O), a hexose sugar freely soluble in water.
- Sodium Chloride, USP is chemically designated NaCl, a white crystalline powder freely soluble in water.
- Water for Injection, USP is chemically designated H2O.
- The flexible plastic container is fabricated from a specially formulated polyvinylchloride. Water can permeate from inside the container into the overwrap but not in amounts sufficient to affect the solution significantly. Solutions inside the plastic container also can leach out certain of the chemical components of the plastic in very small amounts before the expiration period is attained. However, safety of the plastic has been confirmed by tests in animals according to USP biological standards for plastic containers.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Dextran in the drug label.
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Dextran in the drug label.
## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Dextran in the drug label.
# Clinical Studies
There is limited information regarding Clinical Studies of Dextran in the drug label.
# How Supplied
- 10% dextran 40 in 5% Dextrose Injection (Dextran 40 in Dextrose Injection, USP) is supplied in a 500 mL single-dose flexible container (NDC 0409-7418-03). 10% LMD in 0.9% Sodium Chloride Injection (Dextran 40 in Sodium Chloride Injection, USP) is supplied in a 500 mL single-dose flexible container (NDC 0409-7419-03).
## Storage
- Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Protect from freezing.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Dextran in the drug label.
# Precautions with Alcohol
- Alcohol-Dextran interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- LMD IN DEXTROSE
- LMD IN SODIUM CHLORIDE
# Look-Alike Drug Names
There is limited information regarding Dextran Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Dextran | |
52fafce8e0e02f779de5295a892e9a83312ec187 | wikidoc | Dextrin | Dextrin
# Overview
Dextrins are a group of low-molecular-weight carbohydrates produced by the hydrolysis of starch. Dextrins are mixtures of linear α-(1,4)-linked D-glucose polymers starting with an α-(1,6) bond. Because branched amylopectin and glycogen also contain α-(1,6) bonds, which α-amylase cannot hydrolyze in humans, the digest resulting from this action contains a mixture of dextrins. They have the same general formula as carbohydrates but are of shorter chain length. Industrial production is, in general, performed by acidic hydrolysis of potato starch. Dextrins are water-soluble, white to slightly yellow solids that are optically active. Under analysis, dextrins can be detected with iodine solution, giving a red coloration.
The cyclical dextrins are known as cyclodextrins. They are formed by enzymatic degradation of starch by certain bacteria, for example, Bacillus macerans. Cyclodextrins have toroidal structures formed by 6-8 glucose residues.
Dextrins find widespread use in industry, due to their non-toxicity and their low price. They are used as water-soluble glues, as thickening agents in food processing, and as binding agent in pharmaceuticals. In pyrotechnics, they are added to fire formulas, allowing them to solidify as pellets or "stars." Cyclodextrins find additional use in analytical chemistry as a matrix for the separation of hydrophobic substances, and as excipients in pharmaceutical formulations. Not all forms of dextrin are digestible, and indigestible dextrin is sometimes used in fiber supplements.
For example, maltodextrin either can be moderately sweet or have hardly any flavor at all. Maltodextrin is a polysaccharide that is used as a food additive. It is produced from starch and is usually found as a creamy-white hygroscopic powder. Maltodextrin is easily digestible, being absorbed as rapidly as glucose. The CAS registry number of maltodextrin is 9050-36-6.
Maltodextrin can be derived from any starch. In the US, this starch is usually rice, corn or potato; elsewhere, such as in Europe, it is commonly wheat.
This is important for coeliacs, since the wheat-derived maltodextrin can contain traces of gluten. There have been recent reports of coeliac reaction to maltodextrin in the United States. This might be a consequence of the shift of corn to ethanol production and its replacement with wheat in the formulation. The fast food chain, Wendy's, footnotes maltodextrin in its list of gluten-free foods , which may be a sign of their receiving reports of this.
Foods containing maltodextrin may contain traces of amino acids, including glutamic acid as a manufacturing by-product. The amino acids traces would be too small to have any dietary significance. | Dextrin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Dextrins are a group of low-molecular-weight carbohydrates produced by the hydrolysis of starch. Dextrins are mixtures of linear α-(1,4)-linked D-glucose polymers starting with an α-(1,6) bond. Because branched amylopectin and glycogen also contain α-(1,6) bonds, which α-amylase cannot hydrolyze in humans, the digest resulting from this action contains a mixture of dextrins. They have the same general formula as carbohydrates but are of shorter chain length. Industrial production is, in general, performed by acidic hydrolysis of potato starch. Dextrins are water-soluble, white to slightly yellow solids that are optically active. Under analysis, dextrins can be detected with iodine solution, giving a red coloration.
The cyclical dextrins are known as cyclodextrins. They are formed by enzymatic degradation of starch by certain bacteria, for example, Bacillus macerans. Cyclodextrins have toroidal structures formed by 6-8 glucose residues.
Dextrins find widespread use in industry, due to their non-toxicity and their low price. They are used as water-soluble glues, as thickening agents in food processing, and as binding agent in pharmaceuticals. In pyrotechnics, they are added to fire formulas, allowing them to solidify as pellets or "stars." Cyclodextrins find additional use in analytical chemistry as a matrix for the separation of hydrophobic substances, and as excipients in pharmaceutical formulations. Not all forms of dextrin are digestible, and indigestible dextrin is sometimes used in fiber supplements.
For example, maltodextrin either can be moderately sweet or have hardly any flavor at all. Maltodextrin is a polysaccharide that is used as a food additive. It is produced from starch and is usually found as a creamy-white hygroscopic powder. Maltodextrin is easily digestible, being absorbed as rapidly as glucose. The CAS registry number of maltodextrin is 9050-36-6.
Maltodextrin can be derived from any starch. In the US, this starch is usually rice, corn or potato; elsewhere, such as in Europe, it is commonly wheat.
This is important for coeliacs, since the wheat-derived maltodextrin can contain traces of gluten. There have been recent reports of coeliac reaction to maltodextrin in the United States. This might be a consequence of the shift of corn to ethanol production and its replacement with wheat in the formulation. The fast food chain, Wendy's, footnotes maltodextrin in its list of gluten-free foods [2], which may be a sign of their receiving reports of this.
Foods containing maltodextrin may contain traces of amino acids, including glutamic acid as a manufacturing by-product. The amino acids traces would be too small to have any dietary significance. | https://www.wikidoc.org/index.php/Dextrin | |
6cda08880ff58da3ea1c291cbf2ed30064593cdb | wikidoc | Diamond | Diamond
In mineralogy, diamond is the allotrope of carbon where the carbon atoms are arranged in an isometric-hexoctahedral crystal lattice. Its hardness and high dispersion of light make it useful for industrial applications and jewelry. It is the hardest known naturally-occuring mineral. It is possible to treat regular diamonds under a combination of high pressure and high temperature to produce diamonds (known as Type-II diamonds) that are harder than the diamonds used in hardness gauges. Presently, only aggregated diamond nanorods, a material created using ultrahard fullerite (C60) is confirmed to be harder, although other substances such as cubic boron nitride, rhenium diboride and ultrahard fullerite itself are comparable.
Diamonds are specifically renowned as a material with superlative physical qualities; they make excellent abrasives because they can be scratched only by other diamonds, borazon, ultrahard fullerite, rhenium diboride, or aggregated diamond nanorods, which also means they hold a polish extremely well and retain their lustre. Approximately 130 million carats (26,000 kg) are mined annually, with a total value of nearly USD $9 billion, and about 100,000 kg (220,000 lb) are synthesized annually.
The name diamond derives from the ancient Greek ἀδάμας (adamas) "invincible", "untamed", from ἀ- (a-), "un-" + δαμάω (damáo), "to overpower, to tame". They have been treasured as gemstones since their use as religious icons in ancient India and usage in engraving tools also dates to early human history. Popularity of diamonds has risen since the 19th century because of increased supply, improved cutting and polishing techniques, growth in the world economy, and innovative and successful advertising campaigns. They are commonly judged by the “four Cs”: carat, clarity, color, and cut.
Roughly 49% of diamonds originate from central and southern Africa, although significant sources of the mineral have been discovered in Canada, India, Russia, Brazil, and Australia. They are mined from kimberlite and lamproite volcanic pipes, which can bring diamond crystals, originating from deep within the Earth where high pressures and temperatures enable them to form, to the surface. The mining and distribution of natural diamonds are subjects of frequent controversy such as with concerns over the sale of conflict diamonds (aka blood diamonds) by African paramilitary groups.
# Material properties
A diamond is a transparent crystal of tetrahedrally bonded carbon atoms and crystallizes into the face centered cubic diamond lattice structure. Diamonds have been adapted for many uses because of the material's exceptional physical characteristics. Most notable are its extreme hardness, its high dispersion index, and extremely high thermal conductivity (900 – 2320 W/m K). Above 1700 °C (1973 K / 3583 °F), diamond is converted to graphite. Naturally occurring diamonds have a density ranging from 3.15 to 3.53 g/cm³, with very pure diamond typically extremely close to 3.52 g/cm³.
### Hardness
Diamond is the hardest natural material known; hardness is defined as resistance to scratching. Diamond has a hardness of 10 (hardest) on Mohs scale of mineral hardness. Diamond's hardness has been known since antiquity, and is the source of its name.
The hardest diamonds in the world are from the New England area in New South Wales, Australia. These diamonds are generally small, perfect to semiperfect octahedra, and are used to polish other diamonds. Their hardness is considered to be a product of the crystal growth form, which is single stage growth crystal. Most other diamonds show more evidence of multiple growth stages, which produce inclusions, flaws, and defect planes in the crystal lattice, all of which affect their hardness.
The hardness of diamonds contributes to its suitability as a gemstone. Because it can only be scratched by other diamonds, it maintains its polish extremely well. Unlike many other gems, it is well-suited to daily wear because of its resistance to scratching—perhaps contributing to its popularity as the preferred gem in an engagement or wedding rings, which are often worn every day.
Industrial use of diamonds has historically been associated with their hardness; this property makes diamond the ideal material for cutting and grinding tools. As the hardest known naturally-occurring material, diamond can be used to polish, cut, or wear away any material, including other diamonds. However, diamond is a poor choice for machining ferrous alloys at high speeds. At the high temperatures created by high speed machining, carbon is soluble in iron, leading to greatly increased wear on diamond tools as compared to other alternatives. Common industrial adaptations of this ability include diamond-tipped drill bits and saws, or use of diamond powder as an abrasive. Industrial-grade diamonds are either unsuitable for use as gems or synthetically produced, which lowers their value and makes their use economically feasible.
### Electrical conductivity
Other specialized applications also exist or are being developed, including use as semiconductors: some blue diamonds are natural semiconductors, in contrast to most other diamonds, which are excellent electrical insulators. However, substantial conductivity has been observed for undoped diamond when exposed to air.
### Toughness
Toughness relates to a material's ability to resist breakage from forceful impact. The toughness of natural diamond has been measured as 3.4 MN m-3/2, which is good compared to other gemstones, but poor compared to most engineering materials. As with any material, the macroscopic geometry of a diamond contributes to its resistance to breakage. Diamond is therefore more fragile in some orientations than others.
### Color
Diamond color can occur in blue, green, black, translucent white, pink, violet, orange, purple and red, though yellow and brown are by far the most common colors. "Black" diamonds are not truly black, but rather contain numerous dark inclusions that give the gems their dark appearance. Colored diamonds contain impurities or structural defects that cause the coloration, while pure or nearly pure diamonds are transparent and colorless. Most diamond impurities replace a carbon atom in the crystal lattice, known as a carbon flaw. The most common impurity, nitrogen, causes a slight to intense yellow coloration depending upon the type and concentration of nitrogen present. The Gemological Institute of America (GIA) classifies low saturation yellow and brown diamonds as diamonds in the normal color range, and applies a grading scale from 'D' (colorless) to 'Z' (light yellow).
In October 2007 a blue diamond fetched nearly $8 million. The blue hue was a result of trace amounts of boron in the stone's crystal structure.
### Identification
Diamonds can be identified by their high thermal conductivity. Their high refractive index is also indicative, but other materials have similar refractivity. Diamonds do cut glass, but other materials above glass on Mohs scale such as quartz do also. Diamonds easily scratch other diamonds, but this damages both diamonds.
# Natural history
## Formation
The formation of natural diamond requires very specific conditions. Diamond formation requires exposure of carbon-bearing materials to high pressure, ranging approximately between 45 and 60 kilobars, but at a comparatively low temperature range between approximately 1652–2372 °F (900–1300 °C). These conditions are known to be met in two places on Earth; in the lithospheric mantle below relatively stable continental plates, and at the site of a meteorite strike.
### Diamonds formed in cratons
The conditions for diamond formation to happen in the lithospheric mantle occur at considerable depth corresponding to the aforementioned requirements of temperature and pressure. These depths are estimated to be in between 140–190 kilometers (90–120 miles) though occasionally diamonds have crystallized at depths of 300-400 km (180-250 miles) as well. The rate at which temperature changes with increasing depth into the Earth varies greatly in different parts of the Earth. In particular, under oceanic plates the temperature rises more quickly with depth, beyond the range required for diamond formation at the depth required. The correct combination of temperature and pressure is only found in the thick, ancient, and stable parts of continental plates where regions of lithosphere known as cratons exist. Long residence in the cratonic lithosphere allows diamond crystals to grow larger.
Through studies of carbon isotope ratios (similar to the methodology used in carbon dating, except with the stable isotopes C-12 and C-13), it has been shown that the carbon found in diamonds comes from both inorganic and organic sources. Some diamonds, known as harzburgitic, are formed from inorganic carbon originally found deep in the Earth's mantle. In contrast, eclogitic diamonds contain organic carbon from organic detritus that has been pushed down from the surface of the Earth's crust through subduction (see plate tectonics) before transforming into diamond. These two different source carbons have measurably different 13C:12C ratios. Diamonds that have come to the Earth's surface are generally very old, ranging from under 1 billion to 3.3 billion years old.
Diamonds occur most often as euhedral or rounded octahedra and twinned octahedra known as macles or maccles. As diamond's crystal structure has a cubic arrangement of the atoms, they have many facets that belong to a cube, octahedron, rhombicosidodecahedron, tetrakis hexahedron or disdyakis dodecahedron. The crystals can have rounded off and unexpressive edges and can be elongated. Sometimes they are found grown together or form double "twinned" crystals grown together at the surfaces of the octahedron. These different shapes and habits of the diamonds result from differing external circumstances. Diamonds (especially those with rounded crystal faces) are commonly found coated in nyf, an opaque gum-like skin.
### Diamonds and meteorite impact craters
Diamonds can also form in other natural high-pressure events. Very small diamonds, known as microdiamonds or nanodiamonds, have been found in meteorite impact craters. Such impact events create shock zones of high pressure and temperature suitable for diamond formation. Impact-type microdiamonds can be used as one indicator of ancient impact craters.
### Extraterrestrial diamonds
Not all diamonds found on earth originated here. A type of diamond called carbonado diamond that is found in South America and Africa was deposited there via an asteroid impact (not formed from the impact) about 3 billion years ago. These diamonds formed in the intrastellar environment.
Presolar grains in many meteorites found on earth contain nanodiamonds of extraterrestrial origin, probably formed in supernovas.
Some White dwarf stars are believed to have a carbon core. The largest diamond found in the universe, so far, is located 50 light years away in the constellation Centaurus. The Harvard Smithsonian Center for Astrophysics believes the 2,500 mile-wide diamond was once the heart of a star. It is estimated to be ten billion trillion trillion carats, more or less. It was named Lucy, in honor of the Beatle's song "Lucy in the Sky With Diamonds".
## Surfacing
Diamond-bearing rock is brought close to the surface through deep-origin volcanic eruptions. The magma for such a volcano must originate at a depth where diamonds can be formed, 150 km (90 miles) deep or more (three times or more the depth of source magma for most volcanoes); this is a relatively rare occurrence. These typically small surface volcanic craters extend downward in formations known as volcanic pipes. The pipes contain material that was transported toward the surface by volcanic action, but was not ejected before the volcanic activity ceased. During eruption these pipes are open to the surface, resulting in open circulation; many xenoliths of surface rock and even wood and/or fossils are found in volcanic pipes. Diamond-bearing volcanic pipes are closely related to the oldest, coolest regions of continental crust (cratons). This is because cratons are very thick, and their lithospheric mantle extends to great enough depth that diamonds are stable. Not all pipes contain diamonds, and even fewer contain enough diamonds to make mining economically viable.
The magma in volcanic pipes is usually one of two characteristic types, which cool into igneous rock known as either kimberlite or lamproite. The magma itself does not contain diamond; instead, it acts as an elevator that carries deep-formed rocks (xenoliths), minerals (xenocrysts), and fluids upward. These rocks are characteristically rich in magnesium-bearing olivine, pyroxene, and amphibole minerals which are often altered to serpentine by heat and fluids during and after eruption. Certain indicator minerals typically occur within diamondiferous kimberlites and are used as mineralogic tracers by prospectors, who follow the indicator trail back to the volcanic pipe which may contain diamonds. These minerals are rich in chromium (Cr) or titanium (Ti), elements which impart bright colors to the minerals. The most common indicator minerals are chromian garnets (usually bright red Cr-pyrope, and occasionally green ugrandite-series garnets), eclogitic garnets, orange Ti-pyrope, red high-Cr spinels, dark chromite, bright green Cr-diopside, glassy green olivine, black picroilmenite, and magnetite. Kimberlite deposits are known as blue ground for the deeper serpentinized part of the deposits, or as yellow ground for the near surface smectite clay and carbonate weathered and oxidized portion.
Once diamonds have been transported to the surface by magma in a volcanic pipe, they may erode out and be distributed over a large area. A volcanic pipe containing diamonds is known as a primary source of diamonds. Secondary sources of diamonds include all areas where a significant number of diamonds, eroded out of their kimberlite or lamproite matrix, accumulate because of water or wind action. These include alluvial deposits and deposits along existing and ancient shorelines, where loose diamonds tend to accumulate because of their approximate size and density. Diamonds have also rarely been found in deposits left behind by glaciers (notably in Wisconsin and Indiana); however, in contrast to alluvial deposits, glacial deposits are not known to be of significant concentration and are therefore not viable commercial sources of diamond.
# History and gemological characteristics
Diamonds are thought to have been first recognized and mined in India (Golconda being one of them), where significant alluvial deposits of the stone could then be found along the rivers Penner, Krishna and Godavari. Diamonds have been known in India for at least 3000 years but most likely 6000 years. In 1813, Humphry Davy used a lens to concentrate the rays of the sun on a diamond in an atmosphere of oxygen, and showed that the only product of the combustion was carbon dioxide, proving that diamond is composed of carbon. Later, he showed that in an atmosphere devoid of oxygen, diamond is converted to graphite.
The most familiar usage of diamonds today is as gemstones used for adornment a usage which dates back into antiquity. The dispersion of white light into spectral colors, is the primary gemological characteristic of gem diamonds. In the twentieth century, experts in the field of gemology have developed methods of grading diamonds and other gemstones based on the characteristics most important to their value as a gem. Four characteristics, known informally as the four Cs, are now commonly used as the basic descriptors of diamonds: these are carat, cut, color, and clarity.
# The diamond industry
The diamond industry can be broadly separated into two basically distinct categories: one dealing with gem-grade diamonds and another for industrial-grade diamonds. While a large trade in both types of diamonds exists, the two markets act in dramatically different ways.
## Gem diamond industry
A large trade in gem-grade diamonds exists. Unlike precious metals such as gold or platinum, gem diamonds do not trade as a commodity: there is a substantial mark-up in the sale of diamonds, and there is not a very active market for resale of diamonds. One hallmark of the trade in gem-quality diamonds is its remarkable concentration: wholesale trade and diamond cutting is limited to a few locations. 92% of diamond pieces cut in 2003 were in Surat, Gujarat, India. Other important centers of diamond cutting and trading are Antwerp, London, New York, Tel Aviv, Amsterdam. A single company—De Beers—controls a significant proportion of the trade in diamonds. They are based in Johannesburg, South Africa and London, England.
The production and distribution of diamonds is largely consolidated in the hands of a few key players, and concentrated in traditional diamond trading centers. The most important being Antwerp, where 80% of all rough diamonds, 50% of all cut diamonds and more than 50% of all rough, cut and industrial diamonds combined are handled. This makes Antwerp the de facto 'world diamond capital'. New York, however, along with the rest of the United States, is where almost 80% of the world's diamonds are sold, including auction sales. Also, the largest and most unusually shaped rough diamonds end up in New York. The De Beers company, as the world's largest diamond miner holds a clearly dominant position in the industry, and has done so since soon after its founding in 1888 by the British imperialist Cecil Rhodes. De Beers owns or controls a significant portion of the world's rough diamond production facilities (mines) and distribution channels for gem-quality diamonds. The company and its subsidiaries own mines that produce some 40 percent of annual world diamond production. At one time it was thought over 80 percent of the world's rough diamonds passed through the Diamond Trading Company (DTC, a subsidiary of De Beers) in London, but presently the figure is estimated at less than 50 percent.
The De Beers diamond advertising campaign is acknowledged as one of the most successful and innovative campaigns in history. N. W. Ayer & Son, the advertising firm retained by De Beers in the mid-20th century, succeeded in reviving the American diamond market and opened up new markets, even in countries where no diamond tradition had existed before. N.W. Ayer's multifaceted marketing campaign included product placement, advertising the diamond itself rather than the De Beers brand, and building associations with celebrities and royalty. This coordinated campaign has lasted decades and continues today; it is perhaps best captured by the slogan "a diamond is forever".
Further down the supply chain, members of The World Federation of Diamond Bourses (WFDB) act as a medium for wholesale diamond exchange, trading both polished and rough diamonds. The WFDB consists of independent diamond bourses in major cutting centres such as Tel Aviv, Antwerp, Johannesburg and other cities across the USA, Europe and Asia.
In 2000, the WFDB and The International Diamond Manufacturers Association established the World Diamond Council to prevent the trading of diamonds used to fund war and inhumane acts.
WFDB's additional activities also include sponsoring the World Diamond Congress every two years, as well as the establishment of the International Diamond Council (IDC) to oversee diamond grading.
## Industrial diamond industry
The market for industrial-grade diamonds operates much differently from its gem-grade counterpart. Industrial diamonds are valued mostly for their hardness and heat conductivity, making many of the gemological characteristics of diamond, including clarity and color, mostly irrelevant. This helps explain why 80% of mined diamonds (equal to about 100 million carats or 20,000 kg annually), unsuitable for use as gemstones and known as bort, are destined for industrial use. In addition to mined diamonds, synthetic diamonds found industrial applications almost immediately after their invention in the 1950s; another 3 billion carats (600 metric tons) of synthetic diamond is produced annually for industrial use.
The dominant industrial use of diamond is in cutting, drilling, grinding, and polishing. Most uses of diamonds in these technologies do not require large diamonds; in fact, most diamonds that are gem-quality except for their small size, can find an industrial use. Diamonds are embedded in drill tips or saw blades, or ground into a powder for use in grinding and polishing applications. Specialized applications include use in laboratories as containment for high pressure experiments (see diamond anvil), high-performance bearings, and limited use in specialized windows.
With the continuing advances being made in the production of synthetic diamonds, future applications are beginning to become feasible. Garnering much excitement is the possible use of diamond as a semiconductor suitable to build microchips from, or the use of diamond as a heat sink in electronics.
## Diamond supply chain
The diamond supply chain is controlled by a limited number of powerful businesses, and is also highly concentrated in a small number of locations around the world.
### Mining, sources and production
Only a very small fraction of the diamond ore consists of actual diamonds. The ore is crushed, during which care has to be taken in order to prevent larger diamonds from being destroyed in this process and subsequently the particles are sorted by density. Today, diamonds are located in the diamond-rich density fraction with the help of X-ray fluorescence, after which the final sorting steps are done by hand. Before the use of X-rays became commonplace, the separation was done with grease belts; diamonds have a stronger tendency to stick to grease than the other minerals in the ore.
Historically diamonds were known to be found only in alluvial deposits in southern India. India led the world in diamond production from the time of their discovery in approximately the 9th century BCE to the mid-18th century AD, but the commercial potential of these sources had been exhausted by the late 18th century and at that time India was eclipsed by Brazil where the first non-Indian diamonds were found in 1725.
Diamond production of primary deposits (kimberlites and lamproites) only started in the 1870's after the discovery of the Diamond fields in South Africa. Production has increased over time and now an accumulated total of 4.5 billion carats have been mined since that date. Interestingly 20% of that amount has been mined in the last 5 years alone and during the last ten years 9 new mines have started production while 4 more are waiting to be opened soon. Most of these mines are located in Canada, Zimbabwe, Angola, and one in Russia.
In the US, diamonds have been found in Arkansas, Colorado, and Montana. In 2004, a startling discovery of a microscopic diamond in the US led to the January 2008 bulk-sampling of kimberlite pipes in a remote part of Montana.
Today, most commercially viable diamond deposits are in Russia, Botswana, Australia and the Democratic Republic of Congo. In 2005, Russia produced almost one-fifth of the global diamond output, reports the British Geological Survey. Australia boasts the richest diamondiferous pipe with production reaching peak levels of 42 (Expression error: Missing operand for *. ) per year in the 1990's.
There are also commercial deposits being actively mined in the Northwest Territories of Canada, Siberia (mostly in Yakutia territory, for example Mir pipe and Udachnaya pipe), Brazil, and in Northern and Western Australia. Diamond prospectors continue to search the globe for diamond-bearing kimberlite and lamproite pipes.
### "Blood" diamonds
In some of the more politically unstable central African and west African countries, revolutionary groups have taken control of diamond mines, using proceeds from diamond sales to finance their operations. Diamonds sold through this process are known as conflict diamonds or blood diamonds. Major diamond trading corporations continue to fund and fuel these conflicts by doing business with armed groups. In response to public concerns that their diamond purchases were contributing to war and human rights abuses in central Africa and West Africa, the United Nations, the diamond industry and diamond-trading nations introduced the Kimberley Process in 2002, which is aimed at ensuring that conflict diamonds do not become intermixed with the diamonds not controlled by such rebel groups, by providing documentation and certification of diamond exports from producing countries to ensure that the proceeds of sale are not being used to fund criminal or revolutionary activities. Although the Kimberley Process has been moderately successful in limiting the number of conflict diamonds entering the market, conflict diamonds smuggled to market continue to persist to some degree (approx. 2–3% of diamonds traded today are possible conflict diamonds). According to the 2006 book The Heartless Stone, two major flaws still hinder the effectiveness of the Kimberley Process: the relative ease of smuggling diamonds across African borders and giving phony histories, and the violent nature of diamond mining in nations that are not in a technical state of war and whose diamonds are therefore considered "clean."
The Canadian Government has setup a body known as Canadian Diamond Code of Conduct to help authenticate Canadian diamonds. This is a very stringent tracking system of diamonds and helps protect the 'conflict free' label of Canadian diamonds.
Currently, gem production totals nearly 30 million carats (6,000 kg) of cut and polished stones annually, and over 100 million carats (20,000 kg) of mined diamonds are sold for industrial use each year, as are about 100,000 kg of synthesized diamond.
### Distribution
The Diamond Trading Company, or DTC, is a subsidiary of De Beers and markets rough diamonds produced both by De Beers mines and other mines from which it purchases rough diamond production. Once purchased by sightholders, diamonds are cut and polished in preparation for sale as gemstones. The cutting and polishing of rough diamonds is a specialized skill that is concentrated in a limited number of locations worldwide. Traditional diamond cutting centers are Antwerp, Amsterdam, Johannesburg, New York, and Tel Aviv. Recently, diamond cutting centers have been established in China, India, and Thailand. Cutting centers with lower cost of labor, notably Surat in Gujarat, India, handle a larger number of smaller carat diamonds, while smaller quantities of larger or more valuable diamonds are more likely to be handled in Europe or North America. The recent expansion of this industry in India, employing low cost labor, has allowed smaller diamonds to be prepared as gems in greater quantities than was previously economically feasible.
Diamonds which have been prepared as gemstones are sold on diamond exchanges called bourses. There are 26 registered diamond bourses. This is the final tightly controlled step in the diamond supply chain; wholesalers and even retailers are able to buy relatively small lots of diamonds at the bourses, after which they are prepared for final sale to the consumer. Diamonds can be sold already set in jewelry, or as is increasingly popular, sold unset ("loose"). According to the Rio Tinto Group, in 2002 the diamonds produced and released to the market were valued at US$9 billion as rough diamonds, US$14 billion after being cut and polished, US$28 billion in wholesale diamond jewelry, and retail sales of US$57 billion.
## Crater of Diamonds State Park
The Crater of Diamonds State Park is an Arkansas State Park located near Murfreesboro in Pike County, Arkansas, USA containing the only diamond bearing site in the world that is open to the public.
# Synthetics, simulants, and enhancements
Natural diamonds have formed naturally within the earth. Synthetic diamonds are purely manufactured. A diamond simulant is defined as a non-diamond material that is used to simulate the appearance of a diamond. Diamond-simulant gems are often referred to as diamante.
The gemological and industrial uses of diamond have created a large demand for rough stones. The demand for industrial diamonds has long been satisfied in large part by synthetic diamonds, which have been manufactured by various processes for more than half a century. However, in recent years it has become possible to produce gem-quality synthetic diamonds of significant size.
The majority of commercially available synthetic diamonds are yellow in color and produced by so called High Pressure High Temperature (HPHT) processes. The yellow color is caused by nitrogen impurities. Other colors may also be reproduced such as blue, green or pink which are a result of the addition of boron or from irradiation after synthesis.
At present the annual production of gem quality synthetic diamonds is only a few thousand carats, whereas the total production of natural diamonds is around 120 million carats. Although the production of colorless synthetic diamonds is dwarfed by that of natural diamonds, one can only find one fancy colored diamond for every 10,000 colorless ones. Since almost the complete production of synthetic diamonds consists of fancy diamonds, there is a high probability that the larger fancy colored diamonds (over 1.5 carats) will be synthetic.
Today, trained gemologists can generally also distinguish between natural diamonds and synthetic diamonds. Although synthetic and natural diamonds are theoretically identical and indistinguishable from each other, diamonds from each of the two categories usually incorporate their own characteristic imperfections, arising from the circumstances of their creation, that allow them to be distinguished from each other. In the case of synthetic diamonds, for example, depending on the method of production (either high-pressure/high-temperature produced or chemical vapor deposition produced) and the color of the diamond (colored, D-Z color range or D-J color range), several methods of identification can be attempted by a gemologist or gemlab: CVD diamonds can usually be identified by an orange fluorescence, D-J colored diamonds can be screened through the Swiss Gemological Organization's (SSEF) Diamond Spotter, and stones in the D-Z color range can be examined through the DiamondSure UV/visible spectrometer which is a tool developed by De Beers. Similarly, natural diamonds usually have minor imperfections and flaws, such as inclusions of foreign material, that are not seen in synthetic diamonds. The origin of a truly perfect diamond (natural or synthetic) cannot be determined and is largely moot given that perfect diamonds are currently rare from both sources.
A diamond's gem quality, which is not as dependent on material properties as industrial applications, has invited both imitation and the invention of procedures to enhance the gemological properties of natural diamonds. Materials which have similar gemological characteristics to diamond but are not mined or synthetic diamond are known as diamond simulants. The most familiar diamond simulant to most consumers is cubic zirconia (commonly abbreviated as CZ); recently moissanite has also gained popularity and has often been mischaracterized as a diamond simulant, although it is sold and retailed as a replacement for diamond. Both CZ and moissanite are synthetically produced. However, CZ is a diamond simulant. Diamond enhancements are specific treatments, performed on natural diamonds (usually those already cut and polished into a gem), which are designed to better the gemological characteristics of the stone in one or more ways. These include laser drilling to remove inclusions, application of sealants to fill cracks, treatments to improve a white diamond's color grade, and treatments to give fancy color to a white diamond.
Currently, trained gemologists with appropriate equipment are able to distinguish natural diamonds from simulant diamonds, and they can identify all enhanced natural diamonds. Coatings are more and more used to give a diamond simulant such as cubic zirconia a more "diamond-like" appearance. One such substance, which is heavily advertised, is what scientists refer to as "diamond-like carbon". This is an amorphous carbonaceous material that has some physical properties which are similar to that of the diamond. Advertising suggests (rightfully so or not) that such a coating would transfer some of these diamond-like properties to the coated stone, hence enhancing the diamond simulant. However, modern techniques such as Raman Spectroscopy should easily identify such as treatment.
Producing large synthetic diamonds threatens the business model of the diamond industry, and the ultimate effect of the ready availability of gem-quality diamonds at low cost in the future is hard to predict at this time.
The screening machine use for referring treated or enhanced diamonds as well as synthetics is the DiamondSure, and the definitive analytical machine is the DiamondView produce by the DTC and supplied marketed by the GIA. All of the major diamond testing laboratories world wide are required to have these machines. | Diamond
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In mineralogy, diamond is the allotrope of carbon where the carbon atoms are arranged in an isometric-hexoctahedral crystal lattice. Its hardness and high dispersion of light make it useful for industrial applications and jewelry. It is the hardest known naturally-occuring mineral. It is possible to treat regular diamonds under a combination of high pressure and high temperature to produce diamonds (known as Type-II diamonds) that are harder than the diamonds used in hardness gauges.[1] Presently, only aggregated diamond nanorods, a material created using ultrahard fullerite (C60) is confirmed to be harder, although other substances such as cubic boron nitride, rhenium diboride and ultrahard fullerite itself are comparable.
Diamonds are specifically renowned as a material with superlative physical qualities; they make excellent abrasives because they can be scratched only by other diamonds, borazon, ultrahard fullerite, rhenium diboride, or aggregated diamond nanorods, which also means they hold a polish extremely well and retain their lustre. Approximately 130 million carats (26,000 kg) are mined annually, with a total value of nearly USD $9 billion, and about 100,000 kg (220,000 lb) are synthesized annually.[2]
The name diamond derives from the ancient Greek ἀδάμας (adamas) "invincible", "untamed", from ἀ- (a-), "un-" + δαμάω (damáo), "to overpower, to tame". They have been treasured as gemstones since their use as religious icons in ancient India and usage in engraving tools also dates to early human history.[3][4] Popularity of diamonds has risen since the 19th century because of increased supply, improved cutting and polishing techniques, growth in the world economy, and innovative and successful advertising campaigns. They are commonly judged by the “four Cs”: carat, clarity, color, and cut.
Roughly 49% of diamonds originate from central and southern Africa, although significant sources of the mineral have been discovered in Canada, India, Russia, Brazil, and Australia. They are mined from kimberlite and lamproite volcanic pipes, which can bring diamond crystals, originating from deep within the Earth where high pressures and temperatures enable them to form, to the surface. The mining and distribution of natural diamonds are subjects of frequent controversy such as with concerns over the sale of conflict diamonds (aka blood diamonds) by African paramilitary groups.
# Material properties
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A diamond is a transparent crystal of tetrahedrally bonded carbon atoms and crystallizes into the face centered cubic diamond lattice structure. Diamonds have been adapted for many uses because of the material's exceptional physical characteristics. Most notable are its extreme hardness, its high dispersion index, and extremely high thermal conductivity (900 – 2320 W/m K). Above 1700 °C (1973 K / 3583 °F), diamond is converted to graphite[5]. Naturally occurring diamonds have a density ranging from 3.15 to 3.53 g/cm³, with very pure diamond typically extremely close to 3.52 g/cm³.
### Hardness
Diamond is the hardest natural material known; hardness is defined as resistance to scratching.[6] Diamond has a hardness of 10 (hardest) on Mohs scale of mineral hardness.[7] Diamond's hardness has been known since antiquity, and is the source of its name.
The hardest diamonds in the world are from the New England area in New South Wales, Australia. These diamonds are generally small, perfect to semiperfect octahedra, and are used to polish other diamonds. Their hardness is considered to be a product of the crystal growth form, which is single stage growth crystal. Most other diamonds show more evidence of multiple growth stages, which produce inclusions, flaws, and defect planes in the crystal lattice, all of which affect their hardness.[8]
The hardness of diamonds contributes to its suitability as a gemstone. Because it can only be scratched by other diamonds, it maintains its polish extremely well. Unlike many other gems, it is well-suited to daily wear because of its resistance to scratching—perhaps contributing to its popularity as the preferred gem in an engagement or wedding rings, which are often worn every day.
Industrial use of diamonds has historically been associated with their hardness; this property makes diamond the ideal material for cutting and grinding tools. As the hardest known naturally-occurring material, diamond can be used to polish, cut, or wear away any material, including other diamonds. However, diamond is a poor choice for machining ferrous alloys at high speeds. At the high temperatures created by high speed machining, carbon is soluble in iron, leading to greatly increased wear on diamond tools as compared to other alternatives. Common industrial adaptations of this ability include diamond-tipped drill bits and saws, or use of diamond powder as an abrasive. Industrial-grade diamonds are either unsuitable for use as gems or synthetically produced, which lowers their value and makes their use economically feasible.
### Electrical conductivity
Other specialized applications also exist or are being developed, including use as semiconductors: some blue diamonds are natural semiconductors, in contrast to most other diamonds, which are excellent electrical insulators.[7] However, substantial conductivity has been observed for undoped diamond when exposed to air.[9]
### Toughness
Toughness relates to a material's ability to resist breakage from forceful impact. The toughness of natural diamond has been measured as 3.4 MN m-3/2,[10] which is good compared to other gemstones, but poor compared to most engineering materials. As with any material, the macroscopic geometry of a diamond contributes to its resistance to breakage. Diamond is therefore more fragile in some orientations than others.
### Color
Diamond color can occur in blue, green, black, translucent white, pink, violet, orange, purple and red, though yellow and brown are by far the most common colors.[7] "Black" diamonds are not truly black, but rather contain numerous dark inclusions that give the gems their dark appearance. Colored diamonds contain impurities or structural defects that cause the coloration, while pure or nearly pure diamonds are transparent and colorless. Most diamond impurities replace a carbon atom in the crystal lattice, known as a carbon flaw. The most common impurity, nitrogen, causes a slight to intense yellow coloration depending upon the type and concentration of nitrogen present.[7] The Gemological Institute of America (GIA) classifies low saturation yellow and brown diamonds as diamonds in the normal color range, and applies a grading scale from 'D' (colorless) to 'Z' (light yellow).
In October 2007 a blue diamond fetched nearly $8 million. The blue hue was a result of trace amounts of boron in the stone's crystal structure.[11]
### Identification
Diamonds can be identified by their high thermal conductivity. Their high refractive index is also indicative, but other materials have similar refractivity. Diamonds do cut glass, but other materials above glass on Mohs scale such as quartz do also. Diamonds easily scratch other diamonds, but this damages both diamonds.[12]
# Natural history
## Formation
The formation of natural diamond requires very specific conditions. Diamond formation requires exposure of carbon-bearing materials to high pressure, ranging approximately between 45 and 60 kilobars,[13] but at a comparatively low temperature range between approximately 1652–2372 °F (900–1300 °C).[13] These conditions are known to be met in two places on Earth; in the lithospheric mantle below relatively stable continental plates, and at the site of a meteorite strike.
### Diamonds formed in cratons
The conditions for diamond formation to happen in the lithospheric mantle occur at considerable depth corresponding to the aforementioned requirements of temperature and pressure. These depths are estimated to be in between 140–190 kilometers (90–120 miles)[13][7] though occasionally diamonds have crystallized at depths of 300-400 km (180-250 miles) as well.[14] The rate at which temperature changes with increasing depth into the Earth varies greatly in different parts of the Earth. In particular, under oceanic plates the temperature rises more quickly with depth, beyond the range required for diamond formation at the depth required.[13] The correct combination of temperature and pressure is only found in the thick, ancient, and stable parts of continental plates where regions of lithosphere known as cratons exist.[13] Long residence in the cratonic lithosphere allows diamond crystals to grow larger.
Through studies of carbon isotope ratios (similar to the methodology used in carbon dating, except with the stable isotopes C-12 and C-13), it has been shown that the carbon found in diamonds comes from both inorganic and organic sources. Some diamonds, known as harzburgitic, are formed from inorganic carbon originally found deep in the Earth's mantle. In contrast, eclogitic diamonds contain organic carbon from organic detritus that has been pushed down from the surface of the Earth's crust through subduction (see plate tectonics) before transforming into diamond.[7] These two different source carbons have measurably different 13C:12C ratios. Diamonds that have come to the Earth's surface are generally very old, ranging from under 1 billion to 3.3 billion years old.
Diamonds occur most often as euhedral or rounded octahedra and twinned octahedra known as macles or maccles. As diamond's crystal structure has a cubic arrangement of the atoms, they have many facets that belong to a cube, octahedron, rhombicosidodecahedron, tetrakis hexahedron or disdyakis dodecahedron. The crystals can have rounded off and unexpressive edges and can be elongated. Sometimes they are found grown together or form double "twinned" crystals grown together at the surfaces of the octahedron. These different shapes and habits of the diamonds result from differing external circumstances. Diamonds (especially those with rounded crystal faces) are commonly found coated in nyf, an opaque gum-like skin.[15]
### Diamonds and meteorite impact craters
Diamonds can also form in other natural high-pressure events. Very small diamonds, known as microdiamonds or nanodiamonds, have been found in meteorite impact craters. Such impact events create shock zones of high pressure and temperature suitable for diamond formation. Impact-type microdiamonds can be used as one indicator of ancient impact craters.[7]
### Extraterrestrial diamonds
Not all diamonds found on earth originated here. A type of diamond called carbonado diamond that is found in South America and Africa was deposited there via an asteroid impact (not formed from the impact) about 3 billion years ago.[16][17] These diamonds formed in the intrastellar environment.
Presolar grains in many meteorites found on earth contain nanodiamonds of extraterrestrial origin, probably formed in supernovas.
Some White dwarf stars are believed to have a carbon core. The largest diamond found in the universe, so far, is located 50 light years away in the constellation Centaurus. The Harvard Smithsonian Center for Astrophysics believes the 2,500 mile-wide diamond was once the heart of a star. It is estimated to be ten billion trillion trillion carats, more or less. It was named Lucy, in honor of the Beatle's song "Lucy in the Sky With Diamonds".[18][1]
## Surfacing
Diamond-bearing rock is brought close to the surface through deep-origin volcanic eruptions. The magma for such a volcano must originate at a depth where diamonds can be formed,[7] 150 km (90 miles) deep or more (three times or more the depth of source magma for most volcanoes); this is a relatively rare occurrence. These typically small surface volcanic craters extend downward in formations known as volcanic pipes.[7] The pipes contain material that was transported toward the surface by volcanic action, but was not ejected before the volcanic activity ceased. During eruption these pipes are open to the surface, resulting in open circulation; many xenoliths of surface rock and even wood and/or fossils are found in volcanic pipes. Diamond-bearing volcanic pipes are closely related to the oldest, coolest regions of continental crust (cratons). This is because cratons are very thick, and their lithospheric mantle extends to great enough depth that diamonds are stable. Not all pipes contain diamonds, and even fewer contain enough diamonds to make mining economically viable.
The magma in volcanic pipes is usually one of two characteristic types, which cool into igneous rock known as either kimberlite or lamproite.[7] The magma itself does not contain diamond; instead, it acts as an elevator that carries deep-formed rocks (xenoliths), minerals (xenocrysts), and fluids upward. These rocks are characteristically rich in magnesium-bearing olivine, pyroxene, and amphibole minerals[7] which are often altered to serpentine by heat and fluids during and after eruption. Certain indicator minerals typically occur within diamondiferous kimberlites and are used as mineralogic tracers by prospectors, who follow the indicator trail back to the volcanic pipe which may contain diamonds. These minerals are rich in chromium (Cr) or titanium (Ti), elements which impart bright colors to the minerals. The most common indicator minerals are chromian garnets (usually bright red Cr-pyrope, and occasionally green ugrandite-series garnets), eclogitic garnets, orange Ti-pyrope, red high-Cr spinels, dark chromite, bright green Cr-diopside, glassy green olivine, black picroilmenite, and magnetite.[7] Kimberlite deposits are known as blue ground for the deeper serpentinized part of the deposits, or as yellow ground for the near surface smectite clay and carbonate weathered and oxidized portion.
Once diamonds have been transported to the surface by magma in a volcanic pipe, they may erode out and be distributed over a large area. A volcanic pipe containing diamonds is known as a primary source of diamonds. Secondary sources of diamonds include all areas where a significant number of diamonds, eroded out of their kimberlite or lamproite matrix, accumulate because of water or wind action. These include alluvial deposits and deposits along existing and ancient shorelines, where loose diamonds tend to accumulate because of their approximate size and density. Diamonds have also rarely been found in deposits left behind by glaciers (notably in Wisconsin and Indiana); however, in contrast to alluvial deposits, glacial deposits are not known to be of significant concentration and are therefore not viable commercial sources of diamond.
# History and gemological characteristics
Diamonds are thought to have been first recognized and mined in India (Golconda being one of them), where significant alluvial deposits of the stone could then be found along the rivers Penner, Krishna and Godavari. Diamonds have been known in India for at least 3000 years but most likely 6000 years.[19] In 1813, Humphry Davy used a lens to concentrate the rays of the sun on a diamond in an atmosphere of oxygen, and showed that the only product of the combustion was carbon dioxide, proving that diamond is composed of carbon.[20] Later, he showed that in an atmosphere devoid of oxygen, diamond is converted to graphite.
The most familiar usage of diamonds today is as gemstones used for adornment a usage which dates back into antiquity. The dispersion of white light into spectral colors, is the primary gemological characteristic of gem diamonds. In the twentieth century, experts in the field of gemology have developed methods of grading diamonds and other gemstones based on the characteristics most important to their value as a gem. Four characteristics, known informally as the four Cs, are now commonly used as the basic descriptors of diamonds: these are carat, cut, color, and clarity.
# The diamond industry
The diamond industry can be broadly separated into two basically distinct categories: one dealing with gem-grade diamonds and another for industrial-grade diamonds. While a large trade in both types of diamonds exists, the two markets act in dramatically different ways.
## Gem diamond industry
A large trade in gem-grade diamonds exists. Unlike precious metals such as gold or platinum, gem diamonds do not trade as a commodity: there is a substantial mark-up in the sale of diamonds, and there is not a very active market for resale of diamonds. One hallmark of the trade in gem-quality diamonds is its remarkable concentration: wholesale trade and diamond cutting is limited to a few locations. 92% of diamond pieces cut in 2003 were in Surat, Gujarat, India.[1] Other important centers of diamond cutting and trading are Antwerp, London, New York, Tel Aviv, Amsterdam. A single company—De Beers—controls a significant proportion of the trade in diamonds. They are based in Johannesburg, South Africa and London, England.
The production and distribution of diamonds is largely consolidated in the hands of a few key players, and concentrated in traditional diamond trading centers. The most important being Antwerp, where 80% of all rough diamonds, 50% of all cut diamonds and more than 50% of all rough, cut and industrial diamonds combined are handled.[citation needed] This makes Antwerp the de facto 'world diamond capital'. New York, however, along with the rest of the United States, is where almost 80% of the world's diamonds are sold, including auction sales. Also, the largest and most unusually shaped rough diamonds end up in New York. The De Beers company, as the world's largest diamond miner holds a clearly dominant position in the industry, and has done so since soon after its founding in 1888 by the British imperialist Cecil Rhodes. De Beers owns or controls a significant portion of the world's rough diamond production facilities (mines) and distribution channels for gem-quality diamonds. The company and its subsidiaries own mines that produce some 40 percent of annual world diamond production. At one time it was thought over 80 percent of the world's rough diamonds passed through the Diamond Trading Company (DTC, a subsidiary of De Beers) in London, but presently the figure is estimated at less than 50 percent.
The De Beers diamond advertising campaign is acknowledged as one of the most successful and innovative campaigns in history. N. W. Ayer & Son, the advertising firm retained by De Beers in the mid-20th century, succeeded in reviving the American diamond market and opened up new markets, even in countries where no diamond tradition had existed before. N.W. Ayer's multifaceted marketing campaign included product placement, advertising the diamond itself rather than the De Beers brand, and building associations with celebrities and royalty. This coordinated campaign has lasted decades and continues today; it is perhaps best captured by the slogan "a diamond is forever".
Further down the supply chain, members of The World Federation of Diamond Bourses (WFDB) act as a medium for wholesale diamond exchange, trading both polished and rough diamonds. The WFDB consists of independent diamond bourses in major cutting centres such as Tel Aviv, Antwerp, Johannesburg and other cities across the USA, Europe and Asia.
In 2000, the WFDB and The International Diamond Manufacturers Association established the World Diamond Council to prevent the trading of diamonds used to fund war and inhumane acts.
WFDB's additional activities also include sponsoring the World Diamond Congress every two years, as well as the establishment of the International Diamond Council (IDC) to oversee diamond grading.
## Industrial diamond industry
The market for industrial-grade diamonds operates much differently from its gem-grade counterpart. Industrial diamonds are valued mostly for their hardness and heat conductivity, making many of the gemological characteristics of diamond, including clarity and color, mostly irrelevant. This helps explain why 80% of mined diamonds (equal to about 100 million carats or 20,000 kg annually), unsuitable for use as gemstones and known as bort, are destined for industrial use. In addition to mined diamonds, synthetic diamonds found industrial applications almost immediately after their invention in the 1950s; another 3 billion carats (600 metric tons) of synthetic diamond is produced annually for industrial use.
The dominant industrial use of diamond is in cutting, drilling, grinding, and polishing. Most uses of diamonds in these technologies do not require large diamonds; in fact, most diamonds that are gem-quality except for their small size, can find an industrial use. Diamonds are embedded in drill tips or saw blades, or ground into a powder for use in grinding and polishing applications. Specialized applications include use in laboratories as containment for high pressure experiments (see diamond anvil), high-performance bearings, and limited use in specialized windows.
With the continuing advances being made in the production of synthetic diamonds, future applications are beginning to become feasible. Garnering much excitement is the possible use of diamond as a semiconductor suitable to build microchips from, or the use of diamond as a heat sink in electronics.
## Diamond supply chain
The diamond supply chain is controlled by a limited number of powerful businesses, and is also highly concentrated in a small number of locations around the world.
### Mining, sources and production
Only a very small fraction of the diamond ore consists of actual diamonds. The ore is crushed, during which care has to be taken in order to prevent larger diamonds from being destroyed in this process and subsequently the particles are sorted by density. Today, diamonds are located in the diamond-rich density fraction with the help of X-ray fluorescence, after which the final sorting steps are done by hand. Before the use of X-rays became commonplace, the separation was done with grease belts; diamonds have a stronger tendency to stick to grease than the other minerals in the ore.
Historically diamonds were known to be found only in alluvial deposits in southern India.[21] India led the world in diamond production from the time of their discovery in approximately the 9th century BCE[22][19] to the mid-18th century AD, but the commercial potential of these sources had been exhausted by the late 18th century and at that time India was eclipsed by Brazil where the first non-Indian diamonds were found in 1725.[19]
Diamond production of primary deposits (kimberlites and lamproites) only started in the 1870's after the discovery of the Diamond fields in South Africa. Production has increased over time and now an accumulated total of 4.5 billion carats have been mined since that date.[23] Interestingly 20% of that amount has been mined in the last 5 years alone and during the last ten years 9 new mines have started production while 4 more are waiting to be opened soon. Most of these mines are located in Canada, Zimbabwe, Angola, and one in Russia.[23]
In the US, diamonds have been found in Arkansas, Colorado, and Montana.[24][25] In 2004, a startling discovery of a microscopic diamond in the US[26] led to the January 2008 bulk-sampling of kimberlite pipes in a remote part of Montana.[27]
Today, most commercially viable diamond deposits are in Russia, Botswana, Australia and the Democratic Republic of Congo.[28] In 2005, Russia produced almost one-fifth of the global diamond output, reports the British Geological Survey. Australia boasts the richest diamondiferous pipe with production reaching peak levels of 42 (Expression error: Missing operand for *. ) per year in the 1990's.[24]
There are also commercial deposits being actively mined in the Northwest Territories of Canada, Siberia (mostly in Yakutia territory, for example Mir pipe and Udachnaya pipe), Brazil, and in Northern and Western Australia. Diamond prospectors continue to search the globe for diamond-bearing kimberlite and lamproite pipes.
### "Blood" diamonds
In some of the more politically unstable central African and west African countries, revolutionary groups have taken control of diamond mines, using proceeds from diamond sales to finance their operations. Diamonds sold through this process are known as conflict diamonds or blood diamonds. Major diamond trading corporations continue to fund and fuel these conflicts by doing business with armed groups. In response to public concerns that their diamond purchases were contributing to war and human rights abuses in central Africa and West Africa, the United Nations, the diamond industry and diamond-trading nations introduced the Kimberley Process in 2002, which is aimed at ensuring that conflict diamonds do not become intermixed with the diamonds not controlled by such rebel groups, by providing documentation and certification of diamond exports from producing countries to ensure that the proceeds of sale are not being used to fund criminal or revolutionary activities. Although the Kimberley Process has been moderately successful in limiting the number of conflict diamonds entering the market, conflict diamonds smuggled to market continue to persist to some degree (approx. 2–3% of diamonds traded today are possible conflict diamonds[29]). According to the 2006 book The Heartless Stone, two major flaws still hinder the effectiveness of the Kimberley Process: the relative ease of smuggling diamonds across African borders and giving phony histories, and the violent nature of diamond mining in nations that are not in a technical state of war and whose diamonds are therefore considered "clean."[30]
The Canadian Government has setup a body known as Canadian Diamond Code of Conduct[31] to help authenticate Canadian diamonds. This is a very stringent tracking system of diamonds and helps protect the 'conflict free' label of Canadian diamonds.
Currently, gem production totals nearly 30 million carats (6,000 kg) of cut and polished stones annually, and over 100 million carats (20,000 kg) of mined diamonds are sold for industrial use each year, as are about 100,000 kg of synthesized diamond.
### Distribution
The Diamond Trading Company, or DTC, is a subsidiary of De Beers and markets rough diamonds produced both by De Beers mines and other mines from which it purchases rough diamond production. Once purchased by sightholders, diamonds are cut and polished in preparation for sale as gemstones. The cutting and polishing of rough diamonds is a specialized skill that is concentrated in a limited number of locations worldwide. Traditional diamond cutting centers are Antwerp, Amsterdam, Johannesburg, New York, and Tel Aviv. Recently, diamond cutting centers have been established in China, India, and Thailand. Cutting centers with lower cost of labor, notably Surat in Gujarat, India, handle a larger number of smaller carat diamonds, while smaller quantities of larger or more valuable diamonds are more likely to be handled in Europe or North America. The recent expansion of this industry in India, employing low cost labor, has allowed smaller diamonds to be prepared as gems in greater quantities than was previously economically feasible.
Diamonds which have been prepared as gemstones are sold on diamond exchanges called bourses. There are 26 registered diamond bourses.[32] This is the final tightly controlled step in the diamond supply chain; wholesalers and even retailers are able to buy relatively small lots of diamonds at the bourses, after which they are prepared for final sale to the consumer. Diamonds can be sold already set in jewelry, or as is increasingly popular, sold unset ("loose"). According to the Rio Tinto Group, in 2002 the diamonds produced and released to the market were valued at US$9 billion as rough diamonds, US$14 billion after being cut and polished, US$28 billion in wholesale diamond jewelry, and retail sales of US$57 billion. [2]
## Crater of Diamonds State Park
The Crater of Diamonds State Park is an Arkansas State Park located near Murfreesboro in Pike County, Arkansas, USA containing the only diamond bearing site in the world that is open to the public.
# Synthetics, simulants, and enhancements
Natural diamonds have formed naturally within the earth. Synthetic diamonds are purely manufactured. A diamond simulant is defined as a non-diamond material that is used to simulate the appearance of a diamond. Diamond-simulant gems are often referred to as diamante.
The gemological and industrial uses of diamond have created a large demand for rough stones. The demand for industrial diamonds has long been satisfied in large part by synthetic diamonds, which have been manufactured by various processes for more than half a century. However, in recent years it has become possible to produce gem-quality synthetic diamonds of significant size.[33]
The majority of commercially available synthetic diamonds are yellow in color and produced by so called High Pressure High Temperature (HPHT) processes.[34] The yellow color is caused by nitrogen impurities. Other colors may also be reproduced such as blue, green or pink which are a result of the addition of boron or from irradiation after synthesis.[35]
At present the annual production of gem quality synthetic diamonds is only a few thousand carats, whereas the total production of natural diamonds is around 120 million carats. Although the production of colorless synthetic diamonds is dwarfed by that of natural diamonds, one can only find one fancy colored diamond for every 10,000 colorless ones. Since almost the complete production of synthetic diamonds consists of fancy diamonds, there is a high probability that the larger fancy colored diamonds (over 1.5 carats) will be synthetic.[36]
Today, trained gemologists can generally also distinguish between natural diamonds and synthetic diamonds. Although synthetic and natural diamonds are theoretically identical and indistinguishable from each other, diamonds from each of the two categories usually incorporate their own characteristic imperfections, arising from the circumstances of their creation, that allow them to be distinguished from each other. In the case of synthetic diamonds, for example, depending on the method of production (either high-pressure/high-temperature [HPHT] produced or chemical vapor deposition [CVD] produced) and the color of the diamond (colored, D-Z color range or D-J color range), several methods of identification can be attempted by a gemologist or gemlab: CVD diamonds can usually be identified by an orange fluorescence, D-J colored diamonds can be screened through the Swiss Gemological Organization's (SSEF)[37] Diamond Spotter, and stones in the D-Z color range can be examined through the DiamondSure UV/visible spectrometer which is a tool developed by De Beers.[38] Similarly, natural diamonds usually have minor imperfections and flaws, such as inclusions of foreign material, that are not seen in synthetic diamonds. The origin of a truly perfect diamond (natural or synthetic) cannot be determined and is largely moot given that perfect diamonds are currently rare from both sources.
A diamond's gem quality, which is not as dependent on material properties as industrial applications, has invited both imitation and the invention of procedures to enhance the gemological properties of natural diamonds. Materials which have similar gemological characteristics to diamond but are not mined or synthetic diamond are known as diamond simulants. The most familiar diamond simulant to most consumers is cubic zirconia (commonly abbreviated as CZ); recently moissanite has also gained popularity and has often been mischaracterized as a diamond simulant, although it is sold and retailed as a replacement for diamond. Both CZ and moissanite are synthetically produced. However, CZ is a diamond simulant. Diamond enhancements are specific treatments, performed on natural diamonds (usually those already cut and polished into a gem), which are designed to better the gemological characteristics of the stone in one or more ways. These include laser drilling to remove inclusions, application of sealants to fill cracks, treatments to improve a white diamond's color grade, and treatments to give fancy color to a white diamond.
Currently, trained gemologists with appropriate equipment are able to distinguish natural diamonds from simulant diamonds, and they can identify all enhanced natural diamonds. Coatings are more and more used to give a diamond simulant such as cubic zirconia a more "diamond-like" appearance. One such substance, which is heavily advertised, is what scientists refer to as "diamond-like carbon". This is an amorphous carbonaceous material that has some physical properties which are similar to that of the diamond. Advertising suggests (rightfully so or not) that such a coating would transfer some of these diamond-like properties to the coated stone, hence enhancing the diamond simulant. However, modern techniques such as Raman Spectroscopy should easily identify such as treatment.[39]
Producing large synthetic diamonds threatens the business model of the diamond industry, and the ultimate effect of the ready availability of gem-quality diamonds at low cost in the future is hard to predict at this time.
The screening machine use for referring treated or enhanced diamonds as well as synthetics is the DiamondSure, and the definitive analytical machine is the DiamondView produce by the DTC and supplied marketed by the GIA. All of the major diamond testing laboratories world wide are required to have these machines. | https://www.wikidoc.org/index.php/Diamond | |
a33ec3a652d866eda2d20d628088746e0d447d5c | wikidoc | Dicofol | Dicofol
Dicofol is an organochlorine pesticide that is chemically related to DDT. Dicofol is a miticide that is very effective against red spider mite.
One of the intermediates used in its production is DDT. This has caused criticism by many environmentalists; however, the World Health Organization classifies dicofol as a Level III, "slightly hazardous" pesticide. It is known to be harmful to aquatic animals, and can cause eggshell thinning in various species of birds.
# Difference between dicofol and DDT
Dicofol is structurally similar to DDT. It differs from DDT by the replacement of the hydrogen (H) on C-1 by a hydroxyl (OH) [[functional group. One of the intermediates used in its production is DDT.
# Chemistry
Dicofol is usually synthesized from technical DDT. During the synthesis, DDT is first chlorinated to an intermediate, Cl-DDT, followed by hydrolyzing to dicofol.After the synthesis reaction, DDT and Cl-DDT may remain in the dicofol product as impurities.
- Formula: C14H9Cl5O
- Chemical names: 2,2,2-Trichloro-1,1-bis(4-chlorophenyl)ethanol
- Appearance: Pure dicofol is a white crystalline solid. Technical dicofol is a red-brown or amber viscous liquid with an odor like fresh-cut hay.
- Solubility: It is stable under cool and dry conditions, is practically insoluble in water but soluble in organic solvents. Solubility: 0.8 mg/l (25 °C) in water.
- Melting Point: 78.5 - 79.5 °C for pure dicofol, 50 °C for technical dicofol
- Vapor Pressure: Negligible at room temperature
- Molecular Weight: 370.49 g/mol
- Partition Coefficient: 4.2788
- Adsorption Coefficient: 5000 (estimated)
# Impurities
Manufacturing-use dicofol products contain a number of DDT analogs as manufacturing impurities. These include the o,p' and p,p' isomers of DDT, DDE, DDD, and a substance called extra-chlorine DDT or Cl-DOT
# Use and formulations
Foliar spray on agricultural crops and ornamentals, and in or around agricultural and domestic buildings for mite control. It is formulated as emulsifiable concentrates, wettable powders, dusts, ready-to-use liquids, and aerosol sprays. In many countries, dicofol is also used in combination with other pesticides such as the organophosphates, methyl parathion , and dimethoate.
# Producers
Dicofol first appeared in the scientific literature in 1956, and was introduced onto the market by the US-based multinational company Rohm & Haas in 1957. Other current manufacturers include Hindustan (India), Lainco (Spain), and Makhteshim-Agan (Israel). It is sold under a number of trade names, including Kelthane and Acarin.
In 1986, the US Environmental Protection Agency (EPA) temporarily canceled the use of dicofol because relatively high levels of DDT contamination were ending up in the final product. Modern processes can produce technical grade dicofol that contains less than 0.1% DDT.
# Estimated usage as a pesticide
The Pesticide Survey, USA 1987 through 1996, reports that the total annual domestic agricultural usage of dicofol averaged about 860,000 pounds active ingredient (a.i.) for about 720,000 acres (2,910 km²) treated. Most of the area is treated with 2 pounds a.i. or less per application, and the average acre is treated with about 1.2 pounds a.i. per year (1.3 kg/(ha·yr)). Fruits tend to have the highest application rates.
The largest markets for dicofol in terms of total pounds active ingredient are cotton (over 50%) and citrus (almost 30%). Although only about 4% of the cotton acres grown are treated with dicofol, over 60% of all crop acres treated with dicofol are cotton acres. The remaining usage is primarily on other fruits and vegetables. Most of the US usage is in California and Florida.
# Effects
The California Department of Food and Agriculture has one of the world's most extensive incident reporting systems. Between 1982 and 1992, 38 incidents involving dicofol alone were reported: systemic 19 (50%); skin 10 (26%); eye 8 (21%); and eye/skin 1 (3%). The number of incidents per 1,000 applications for all illnesses ranged from 0.11 to 0.21.
The US National Pesticides Telecommunications Network database collected reports from 1984 to 1991 showing 91 human, 9 animal and 31 other poisoning incidents for a total of 131 incidents involving dicofol from 571 phone calls made to the hotline.
An assessment of dicofol by the UK Pesticides Safety Directorate in 1996 found that residues in apples, pears, blackcurrants and strawberries were higher than expected.
There is no established US maximum contaminant level (MCL) or health advisory levels for residues of dicofol in drinking water. In the European Union, the maximum level is the same for all active ingredients 0.1 mg/l.
In 1990, the use of dicofol was suspended in Sweden for environmental reasons. In Switzerland its use is permitted for research purposes only. Throughout the European Union dicofol containing more than lg/kg (0.1%) of DDT or DDT related compounds cannot be used.
The 1998 US EPA review of dicofol recommended a number of changes in order to protect the environment and wildlife. Dicofol applications are limited to no more than one per year. In the UK, the maximum number of treatments permitted is two per year for apples and hops, and two per crop for strawberries, protected crops and tomatoes.
In 1980, an accident at the US Tower Chemical Company led to a release of dicofol into Lake Apopka in Florida. Ten years later Dr Guillette of Florida University linked this incident to a subsequent decline in the fertility of alligators in the lake. The US EPA is still not clear whether dicofol is involved in the reproductive failure of the alligator population following the accidental spill.
# Toxicity
It is classified by the World Health Organisation as a Class III, 'slightly hazardous' pesticide.
The acute oral LD50 for dicofol is 587 mg/kg for rats.
Dicofol is a nerve poison. The exact mode of action is not known, although in mammals it causes hyperstimulation of nerve transmission along nerve axons (cells). This effect is thought to be related to the inhibition of certain enzymes in the central nervous system.
Symptoms of ingestion and/or respiratory exposure include nausea, dizziness, weakness and vomiting; dermal exposure may cause skin irritation or a rash; and eye contact may cause conjuctivitis. Poisoning may affect the liver, kidneys or the central nervous system. Very severe cases may result in convulsions, coma, or death from respiratory failure.
Dicofol can be stored in fatty tissue. Intense activity or starvation may mobilize the chemical, resulting in the reappearance of toxic symptoms long after actual exposure.
# Chronic effects
Tests on laboratory animals show that the primary effects after long term exposure to dicofol include increases in liver weight and enzyme induction in the rat, mouse and dog.
There are also effects relating to altered adrenocorticoid metabolism (part of the hormonal system). In the rat hormonal changes were accompanied by the histological observation of vacuolation (empty cavities) of the cells of the adrenal cortex.
# Carcinogenecity
The US EPA has classified dicofol as a Group C, possible human carcinogen. There is limited evidence that it may cause cancer in laboratory animals, but there is no evidence that it causes cancer in humans. This classification was based on animal test data that showed an increase in the incidence of liver adenomas (benign tumour) and combined liver adenomas and carcinomas in male mice.
# Reproductive effects
Reproductive effects in rat offspring have been observed only at doses high enough to also cause toxic effects on the livers, ovaries, and feeding behavior of the parents. Rats fed diets containing dicofol through two generations exhibited adverse effects on the survival and/or growth of newborns at 6.25 and 12.5 mg/kg/day
- Teratogenic effects: No teratogenic effects are observed when rats were given up to 25 mg/kg/day on days 6 through 15 of pregnancy
- Mutagenic effects: Laboratory tests have shown that dicofol is not mutagenic
- Endocrine disruption: Evidence for dicofol to cause endocrine disruption is suggestive, but not definitive
A 2007 study by the California Department of Public Health found that women in the first eight weeks of pregnancy who live near farm fields sprayed with dicofol and the related organochloride pesticide endosulfan are several times more likely to give birth to children with autism. These results are highly preliminary due to the small number of women and children involved and lack of evidence from other studies.
# Metabolism
Dicofol is converted in rats to the metabolites 4,4'-dichloro-benzophenone and 4,4'-dichlorodicofol.
Studies of the metabolism of dicofol in rats, mice, and rabbits have shown that ingested dicofol is rapidly absorbed, distributed primarily to fat, and readily eliminated in feces. When mice were given a single oral dose of 25 mg/kg dicofol, approximately 60% of the dose was eliminated within 96 hours, 20% in the urine, and 40% in the feces. Concentrations in body tissues peaked between 24 and 48 hours following dosing, with 10% of the dose found in fat, followed by the liver and other tissues. Levels in tissues other than fat declined sharply after the peak.
# Ecological effects
Effects on birds: Dicofol is slightly toxic to birds. The 8-day dietary LC50 is 3010 ppm in bobwhite quail, 1418 ppm in Japanese quail, and 2126 ppm in ring-necked pheasant. Eggshell thinning and reduced offspring survival were noted in the mallard duck, American kestrel, ring dove, and screech owl.
Effects on aquatic organisms: Dicofol is highly toxic to fish, aquatic invertebrates, and algae. The LC50 is 0.12 mg/L in rainbow trout, 0.37 mg/L in sheepshead minnow, 0.06 mg/L in mysid shrimp, 0.015 mg/L in shell oysters, and 0.075 mg/L in algae.
Effects on other organisms: Dicofol is not toxic to bees.
# Degradation
Breakdown in soil and groundwater: Dicofol is moderately persistent in soil, with a half-life of 60 days. Dicofol is susceptible to chemical breakdown in moist soils. It is also subject to degradation by UV light. In a silty loam soil, its photodegradation half-life was 30 days. Under anaerobic soil conditions, the half-life for dicofol was 15.9 days.
Dicofol is practically insoluble in water and adsorbs very strongly to soil particles. It is therefore nearly immobile in soils and unlikely to infiltrate groundwater. Even in sandy soil, dicofol was not detected below the top 3 inches in standard soil column tests. It is possible for dicofol to enter surface waters when soil erosion occurs.
Breakdown in water: Dicofol degrades in water or when exposed to UV light at pH levels above 7. Its half-life in solution at pH 5 is 47 to 85 days. Because of its very high absorption coefficient (Koc), dicofol is expected to adsorb to sediment when released into open waters.
Breakdown in vegetation: In a number of studies, dicofol residues on treated plant tissues have been shown to remain unchanged for up to 2 years. | Dicofol
Dicofol is an organochlorine pesticide that is chemically related to DDT. Dicofol is a miticide that is very effective against red spider mite.
One of the intermediates used in its production is DDT. This has caused criticism by many environmentalists; however, the World Health Organization classifies dicofol as a Level III, "slightly hazardous" pesticide. It is known to be harmful to aquatic animals, and can cause eggshell thinning in various species of birds.
# Difference between dicofol and DDT
Dicofol is structurally similar to DDT. It differs from DDT by the replacement of the hydrogen (H) on C-1 by a hydroxyl (OH) [[functional group. One of the intermediates used in its production is DDT.
# Chemistry
Dicofol is usually synthesized from technical DDT. During the synthesis, DDT is first chlorinated to an intermediate, Cl-DDT, followed by hydrolyzing to dicofol.After the synthesis reaction, DDT and Cl-DDT may remain in the dicofol product as impurities.
- Formula: C14H9Cl5O
- Chemical names: 2,2,2-Trichloro-1,1-bis(4-chlorophenyl)ethanol
- Appearance: Pure dicofol is a white crystalline solid. Technical dicofol is a red-brown or amber viscous liquid with an odor like fresh-cut hay.
- Solubility: It is stable under cool and dry conditions, is practically insoluble in water but soluble in organic solvents. Solubility: 0.8 mg/l (25 °C) in water.
- Melting Point: 78.5 - 79.5 °C for pure dicofol, 50 °C for technical dicofol
- Vapor Pressure: Negligible at room temperature
- Molecular Weight: 370.49 g/mol
- Partition Coefficient: 4.2788
- Adsorption Coefficient: 5000 (estimated)
# Impurities
Manufacturing-use dicofol products contain a number of DDT analogs as manufacturing impurities. These include the o,p' and p,p' isomers of DDT, DDE, DDD, and a substance called extra-chlorine DDT or Cl-DOT
# Use and formulations
Foliar spray on agricultural crops and ornamentals, and in or around agricultural and domestic buildings for mite control. It is formulated as emulsifiable concentrates, wettable powders, dusts, ready-to-use liquids, and aerosol sprays. In many countries, dicofol is also used in combination with other pesticides such as the organophosphates, methyl parathion , and dimethoate.
# Producers
Dicofol first appeared in the scientific literature in 1956, and was introduced onto the market by the US-based multinational company Rohm & Haas in 1957. Other current manufacturers include Hindustan (India), Lainco (Spain), and Makhteshim-Agan (Israel). It is sold under a number of trade names, including Kelthane and Acarin.
In 1986, the US Environmental Protection Agency (EPA) temporarily canceled the use of dicofol because relatively high levels of DDT contamination were ending up in the final product. Modern processes can produce technical grade dicofol that contains less than 0.1% DDT.
# Estimated usage as a pesticide
The Pesticide Survey, USA 1987 through 1996, reports that the total annual domestic agricultural usage of dicofol averaged about 860,000 pounds active ingredient (a.i.) for about 720,000 acres (2,910 km²) treated. Most of the area is treated with 2 pounds a.i. or less per application, and the average acre is treated with about 1.2 pounds a.i. per year (1.3 kg/(ha·yr)). Fruits tend to have the highest application rates.
The largest markets for dicofol in terms of total pounds active ingredient are cotton (over 50%) and citrus (almost 30%). Although only about 4% of the cotton acres grown are treated with dicofol, over 60% of all crop acres treated with dicofol are cotton acres. The remaining usage is primarily on other fruits and vegetables. Most of the US usage is in California and Florida.
# Effects
The California Department of Food and Agriculture has one of the world's most extensive incident reporting systems. Between 1982 and 1992, 38 incidents involving dicofol alone were reported: systemic 19 (50%); skin 10 (26%); eye 8 (21%); and eye/skin 1 (3%). The number of incidents per 1,000 applications for all illnesses ranged from 0.11 to 0.21.
The US National Pesticides Telecommunications Network database collected reports from 1984 to 1991 showing 91 human, 9 animal and 31 other poisoning incidents for a total of 131 incidents involving dicofol from 571 phone calls made to the hotline.
An assessment of dicofol by the UK Pesticides Safety Directorate in 1996 found that residues in apples, pears, blackcurrants and strawberries were higher than expected.
There is no established US maximum contaminant level (MCL) or health advisory levels for residues of dicofol in drinking water. In the European Union, the maximum level is the same for all active ingredients 0.1 mg/l.
In 1990, the use of dicofol was suspended in Sweden for environmental reasons. In Switzerland its use is permitted for research purposes only. Throughout the European Union dicofol containing more than lg/kg (0.1%) of DDT or DDT related compounds cannot be used.
The 1998 US EPA review of dicofol recommended a number of changes in order to protect the environment and wildlife. Dicofol applications are limited to no more than one per year. In the UK, the maximum number of treatments permitted is two per year for apples and hops, and two per crop for strawberries, protected crops and tomatoes.
In 1980, an accident at the US Tower Chemical Company led to a release of dicofol into Lake Apopka in Florida. Ten years later Dr Guillette of Florida University linked this incident to a subsequent decline in the fertility of alligators in the lake. The US EPA is still not clear whether dicofol is involved in the reproductive failure of the alligator population following the accidental spill.
# Toxicity
It is classified by the World Health Organisation as a Class III, 'slightly hazardous' pesticide.
The acute oral LD50 for dicofol is 587 mg/kg for rats.
Dicofol is a nerve poison. The exact mode of action is not known, although in mammals it causes hyperstimulation of nerve transmission along nerve axons (cells). This effect is thought to be related to the inhibition of certain enzymes in the central nervous system.
Symptoms of ingestion and/or respiratory exposure include nausea, dizziness, weakness and vomiting; dermal exposure may cause skin irritation or a rash; and eye contact may cause conjuctivitis. Poisoning may affect the liver, kidneys or the central nervous system. Very severe cases may result in convulsions, coma, or death from respiratory failure.
Dicofol can be stored in fatty tissue. Intense activity or starvation may mobilize the chemical, resulting in the reappearance of toxic symptoms long after actual exposure.
# Chronic effects
Tests on laboratory animals show that the primary effects after long term exposure to dicofol include increases in liver weight and enzyme induction in the rat, mouse and dog.
There are also effects relating to altered adrenocorticoid metabolism (part of the hormonal system). In the rat hormonal changes were accompanied by the histological observation of vacuolation (empty cavities) of the cells of the adrenal cortex.
# Carcinogenecity
The US EPA has classified dicofol as a Group C, possible human carcinogen. There is limited evidence that it may cause cancer in laboratory animals, but there is no evidence that it causes cancer in humans. This classification was based on animal test data that showed an increase in the incidence of liver adenomas (benign tumour) and combined liver adenomas and carcinomas in male mice.
# Reproductive effects
Reproductive effects in rat offspring have been observed only at doses high enough to also cause toxic effects on the livers, ovaries, and feeding behavior of the parents. Rats fed diets containing dicofol through two generations exhibited adverse effects on the survival and/or growth of newborns at 6.25 and 12.5 mg/kg/day
- Teratogenic effects: No teratogenic effects are observed when rats were given up to 25 mg/kg/day on days 6 through 15 of pregnancy
- Mutagenic effects: Laboratory tests have shown that dicofol is not mutagenic
- Endocrine disruption: Evidence for dicofol to cause endocrine disruption is suggestive, but not definitive
A 2007 study by the California Department of Public Health found that women in the first eight weeks of pregnancy who live near farm fields sprayed with dicofol and the related organochloride pesticide endosulfan are several times more likely to give birth to children with autism. These results are highly preliminary due to the small number of women and children involved and lack of evidence from other studies.[1]
# Metabolism
Dicofol is converted in rats to the metabolites 4,4'-dichloro-benzophenone and 4,4'-dichlorodicofol.
Studies of the metabolism of dicofol in rats, mice, and rabbits have shown that ingested dicofol is rapidly absorbed, distributed primarily to fat, and readily eliminated in feces. When mice were given a single oral dose of 25 mg/kg dicofol, approximately 60% of the dose was eliminated within 96 hours, 20% in the urine, and 40% in the feces. Concentrations in body tissues peaked between 24 and 48 hours following dosing, with 10% of the dose found in fat, followed by the liver and other tissues. Levels in tissues other than fat declined sharply after the peak.
# Ecological effects
Effects on birds: Dicofol is slightly toxic to birds. The 8-day dietary LC50 is 3010 ppm in bobwhite quail, 1418 ppm in Japanese quail, and 2126 ppm in ring-necked pheasant. Eggshell thinning and reduced offspring survival were noted in the mallard duck, American kestrel, ring dove, and screech owl.
Effects on aquatic organisms: Dicofol is highly toxic to fish, aquatic invertebrates, and algae. The LC50 is 0.12 mg/L in rainbow trout, 0.37 mg/L in sheepshead minnow, 0.06 mg/L in mysid shrimp, 0.015 mg/L in shell oysters, and 0.075 mg/L in algae.
Effects on other organisms: Dicofol is not toxic to bees.
# Degradation
Breakdown in soil and groundwater: Dicofol is moderately persistent in soil, with a half-life of 60 days. Dicofol is susceptible to chemical breakdown in moist soils. It is also subject to degradation by UV light. In a silty loam soil, its photodegradation half-life was 30 days. Under anaerobic soil conditions, the half-life for dicofol was 15.9 days.
Dicofol is practically insoluble in water and adsorbs very strongly to soil particles. It is therefore nearly immobile in soils and unlikely to infiltrate groundwater. Even in sandy soil, dicofol was not detected below the top 3 inches in standard soil column tests. It is possible for dicofol to enter surface waters when soil erosion occurs.
Breakdown in water: Dicofol degrades in water or when exposed to UV light at pH levels above 7. Its half-life in solution at pH 5 is 47 to 85 days. Because of its very high absorption coefficient (Koc), dicofol is expected to adsorb to sediment when released into open waters.
Breakdown in vegetation: In a number of studies, dicofol residues on treated plant tissues have been shown to remain unchanged for up to 2 years. | https://www.wikidoc.org/index.php/Dicofol | |
73f3059bacf83233e93dec59af354ab61c62e7fb | wikidoc | Phenols | Phenols
In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of a hydroxyl group (-O H) attached to an aromatic hydrocarbon group. The simplest of the class is phenol (C6H5OH).
Although similar to alcohols, phenols have unique properties and are not classified as alcohols (since the hydroxyl group is not bonded to a saturated carbon atom). They have relatively higher acidities due to the aromatic ring tightly coupling with the oxygen and a relatively loose bond between the oxygen and hydrogen. The acidity of the hydroxyl group in phenols is commonly intermediate between that of aliphatic alcohols and carboxylic acids (their pKa is usually comprised between 10 and 12). Loss of a positive hydrogen ion (H+) from the hydroxyl group of a phenol forms a negative phenolate ion.
Some phenols are germicidal and are used in formulating disinfectants. Others possess estrogenic or endocrine disrupting activity.
# Synthesis of phenols
Several laboratory methods for the synthesis of phenols:
- by an ester rearrangement in the Fries rearrangement
- by a rearrangement of N-phenylhydroxylamines in the Bamberger rearrangement
- by hydrolysis of phenolic esters or ethers
- by reduction of quinones
- by replacement of an aromatic amine by an hydroxyl group with water and sodium bisulfite in the Bucherer reaction
- by hydrolysis of diazonium salts
- by oligomerisation with formaldehyde + base catalysed reaction with epichlorohydrine to epoxi resin components
- by reaction with acetone/ketones to e.g. Bisphenol A, an important monomer for resins, e.g. polycarbonate(PC), epoxi resins
- by a rearrangement reaction of dienones in the dienone phenol rearrangement :
# Reactions of phenols
Phenols react in a wide variety of ways.
- Esterification reactions and ether formation
- Electrophilic aromatic substitutions as the hydroxyl group is activating, for example synthesis of calixarenes
- Reaction of naphtols and hydrazines and sodium bisulfite in the Bucherer carbazole synthesis
- Oxidative cleavage, for instance cleavage of 1,2-dihydroxybenzene to the monomethylester of 2,4 hexadienedioic acid with oxygen, copper chloride in pyridine
- Oxidative de-aromatization to quinones also known as the Teuber reaction. Oxidizing reagents are Fremy's salt and oxone . In reaction depicted below 3,4,5-trimethylphenol reacts with singlet oxygen generated from oxone/sodium carbonate in an acetonitrile/water mixture to a para-peroxyquinole. This hydroperoxide is oxidized to the quinole with sodium thiosulphate.
- Phenols are oxidized to benzenediols in the Elbs persulfate oxidation
- Phenolate anions (deriving from phenols by the loss of H+) can act as ligands towards metal cations
# Phenolic compounds
## Medicinals | Phenols
In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of a hydroxyl group (-O H) attached to an aromatic hydrocarbon group. The simplest of the class is phenol (C6H5OH).
Although similar to alcohols, phenols have unique properties and are not classified as alcohols (since the hydroxyl group is not bonded to a saturated carbon atom). They have relatively higher acidities due to the aromatic ring tightly coupling with the oxygen and a relatively loose bond between the oxygen and hydrogen. The acidity of the hydroxyl group in phenols is commonly intermediate between that of aliphatic alcohols and carboxylic acids (their pKa is usually comprised between 10 and 12). Loss of a positive hydrogen ion (H+) from the hydroxyl group of a phenol forms a negative phenolate ion.
Some phenols are germicidal and are used in formulating disinfectants. Others possess estrogenic or endocrine disrupting activity.
# Synthesis of phenols
Several laboratory methods for the synthesis of phenols:
- by an ester rearrangement in the Fries rearrangement
- by a rearrangement of N-phenylhydroxylamines in the Bamberger rearrangement
- by hydrolysis of phenolic esters or ethers
- by reduction of quinones
- by replacement of an aromatic amine by an hydroxyl group with water and sodium bisulfite in the Bucherer reaction
- by hydrolysis of diazonium salts
- by oligomerisation with formaldehyde + base catalysed reaction with epichlorohydrine to epoxi resin components
- by reaction with acetone/ketones to e.g. Bisphenol A, an important monomer for resins, e.g. polycarbonate(PC), epoxi resins
- by a rearrangement reaction of dienones [1] in the dienone phenol rearrangement [2]:
# Reactions of phenols
Phenols react in a wide variety of ways.
- Esterification reactions and ether formation
- Electrophilic aromatic substitutions as the hydroxyl group is activating, for example synthesis of calixarenes [3]
- Reaction of naphtols and hydrazines and sodium bisulfite in the Bucherer carbazole synthesis
- Oxidative cleavage, for instance cleavage of 1,2-dihydroxybenzene to the monomethylester of 2,4 hexadienedioic acid with oxygen, copper chloride in pyridine [4]
- Oxidative de-aromatization to quinones also known as the Teuber reaction. Oxidizing reagents are Fremy's salt [5] and oxone [6]. In reaction depicted below 3,4,5-trimethylphenol reacts with singlet oxygen generated from oxone/sodium carbonate in an acetonitrile/water mixture to a para-peroxyquinole. This hydroperoxide is oxidized to the quinole with sodium thiosulphate.
- Phenols are oxidized to benzenediols in the Elbs persulfate oxidation
- Phenolate anions (deriving from phenols by the loss of H+) can act as ligands towards metal cations
# Phenolic compounds
## Medicinals | https://www.wikidoc.org/index.php/Dienone_phenol_rearrangement | |
0ba51fdb0c76dffefe6632507df80d11d9b8c695 | wikidoc | Dimebon | Dimebon
Dimebon (Dimebolin) is an antihistamine drug which has been used clinically in Russia since 1983.
Recently Dimebolin has attracted renewed interest after being shown to have positive effects on persons suffering from Alzheimer’s disease. Animal studies showing potential beneficial effects on Alzheimer's disease models were shown in Russian research in 2000. Preliminary results from human trials have also been promising. In an initial six-month phase II trial, results have shown that at 12 months there was significant improvement over placebo.
Dimebolin is an orally active small molecule that has been shown to inhibit brain cell death in preclinical studies of Alzheimer's disease and Huntington's disease, making it a potential treatment for these and other neurodegenerative diseases. Research suggests that Dimebon may also have cognition-enhancing effects in healthy individuals, in the absence of neurodegenerative disease pathology.
Dimebon appears to operate through multiple mechanisms of action, both blocking the action of neurotoxic beta-amyloid proteins and inhibiting L-type calcium channels, modulating the action of AMPA and NMDA glutamate receptors, and may exert a neuroprotective effect by blocking a novel target that involves mitochondrial pores, which are believed to play a role in the cell death that is associated with neurodegenerative diseases and the aging process. Research is continuing in both Russia and western nations into the potential applications of Dimebon as a neuroprotective and potential nootropic. | Dimebon
Dimebon (Dimebolin) is an antihistamine drug which has been used clinically in Russia since 1983.[1]
Recently Dimebolin has attracted renewed interest after being shown to have positive effects on persons suffering from Alzheimer’s disease. Animal studies showing potential beneficial effects on Alzheimer's disease models were shown in Russian research in 2000.[2] Preliminary results from human trials have also been promising. In an initial six-month phase II trial, results have shown that at 12 months there was significant improvement over placebo. [3]
Dimebolin is an orally active small molecule that has been shown to inhibit brain cell death in preclinical studies of Alzheimer's disease and Huntington's disease, making it a potential treatment for these and other neurodegenerative diseases. Research suggests that Dimebon may also have cognition-enhancing effects in healthy individuals, in the absence of neurodegenerative disease pathology.[4]
Dimebon appears to operate through multiple mechanisms of action, both blocking the action of neurotoxic beta-amyloid proteins and inhibiting L-type calcium channels,[5] modulating the action of AMPA and NMDA glutamate receptors,[6] and may exert a neuroprotective effect by blocking a novel target that involves mitochondrial pores,[7] which are believed to play a role in the cell death that is associated with neurodegenerative diseases and the aging process. [8] Research is continuing in both Russia and western nations into the potential applications of Dimebon as a neuroprotective and potential nootropic. [9] | https://www.wikidoc.org/index.php/Dimebon | |
bb527de62ae2e7df13f5c425d3e93220ef078d85 | wikidoc | Dioptre | Dioptre
A dioptre, or diopter, is a unit of measurement of the optical power of a lens or curved mirror, which is equal to the reciprocal of the focal length measured in metres (that is, 1/metres). For example, a 3 dioptre lens brings parallel rays of light to focus at 1/3 metre. The same unit is also sometimes used for other reciprocals of distance, particularly radii of curvature and the vergence of optical beams. The term was proposed by French ophthalmologist Felix Monoyer in 1872.
Though the dioptre is based on the SI-metric system it has not been included in the standard so that there is no international name or abbreviation for this unit of measurement - within the international system of units this unit for optical power would need to be specified explicitly as the inverse metre (m-1). However most languages have borrowed the original name and some national standardization bodies like DIN specify a unit name (dioptrie, dioptria, ..) and derived unit symbol "dpt".
Quantifying a lens in terms of its optical power rather than its focal length is useful because when relatively thin lenses are placed close together their powers approximately add. Thus a thin 2-dioptre lens placed close to a thin 0.5-dioptre lens yields almost the same focal length as a 2.5-dioptre lens would have. This approximation enables an optometrist to prescribe corrective lenses as a simple correction to the eye's optical power, rather than doing a detailed analysis of the entire optical system (the eye and the lens).
Since optical power is approximately additive, it can also be used to adjust a basic prescription for reading, e.g. an optometrist, having determined that a myopic person requires a basic correction of, say, −2 dioptres to restore normal distance vision, might then make a further prescription of 'add 1' for reading, to make up for lack of accommodation (ability to alter focus). This is the same as saying that −1 dioptre lenses are prescribed for reading.
In humans, the total convergence power of the relaxed eye is approximately 60 dioptres. The cornea accounts for approximately two-thirds of this refractive power and the crystalline lens contributes the remaining third. In focusing, the ciliary muscle contracts to reduce the tension or stress transferred to the lens by the suspensory ligaments. This results in increased convexity of the lens which in turn increases the optical power of the eye. As humans age, the amplitude of accommodation reduces from approximately 15 to 20 dioptres in the very young, to about 10 dioptres at age 25, to around 1 dioptre at 50 and over.
Convex lenses have positive dioptric value and are generally used to correct hyperopia (farsightedness) or to allow people with presbyopia (the limited accommodation of advancing age) to read at close range. Concave lenses have negative dioptric value and generally correct myopia (nearsightedness). Typical glasses for mild myopia will have a power of −1.00 to −3.00 dioptres, while over the counter reading glasses will be rated at +1.00 to +3.00 dioptres. Optometrists usually measure refractive error using lenses graded in steps of 0.25 dioptres.
The dioptre can also be used as a measurement of curvature equal to the reciprocal of the radius measured in metres. For example, a circle with a radius of 1/2 metre has a curvature of 2 dioptres. If the curvature of a surface of a lens is C and the index of refraction is n, the focusing power is ɸ = (n − 1)C. If both surfaces of the lens are curved, consider their curvatures as positive toward the lens and add them. This will give approximately the right result, as long as the thickness of the lens is much less than the radius of curvature of one of the surfaces. For a mirror the focusing power is ɸ = 2C.
# Relation to magnifying power
The magnifying power of a simple magnifier is related to its optical power. This is covered in detail in the articles on magnification and magnifying glasses. | Dioptre
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
A dioptre, or diopter, is a unit of measurement of the optical power of a lens or curved mirror, which is equal to the reciprocal of the focal length measured in metres (that is, 1/metres). For example, a 3 dioptre lens brings parallel rays of light to focus at 1/3 metre. The same unit is also sometimes used for other reciprocals of distance, particularly radii of curvature and the vergence of optical beams. The term was proposed by French ophthalmologist Felix Monoyer in 1872.[1][2]
Though the dioptre is based on the SI-metric system it has not been included in the standard so that there is no international name or abbreviation for this unit of measurement - within the international system of units this unit for optical power would need to be specified explicitly as the inverse metre (m-1). However most languages have borrowed the original name and some national standardization bodies like DIN specify a unit name (dioptrie, dioptria, ..) and derived unit symbol "dpt".
Quantifying a lens in terms of its optical power rather than its focal length is useful because when relatively thin lenses are placed close together their powers approximately add. Thus a thin 2-dioptre lens placed close to a thin 0.5-dioptre lens yields almost the same focal length as a 2.5-dioptre lens would have. This approximation enables an optometrist to prescribe corrective lenses as a simple correction to the eye's optical power, rather than doing a detailed analysis of the entire optical system (the eye and the lens).
Since optical power is approximately additive, it can also be used to adjust a basic prescription for reading, e.g. an optometrist, having determined that a myopic person requires a basic correction of, say, −2 dioptres to restore normal distance vision, might then make a further prescription of 'add 1' for reading, to make up for lack of accommodation (ability to alter focus). This is the same as saying that −1 dioptre lenses are prescribed for reading.
In humans, the total convergence power of the relaxed eye is approximately 60 dioptres. The cornea accounts for approximately two-thirds of this refractive power and the crystalline lens contributes the remaining third.[3] In focusing, the ciliary muscle contracts to reduce the tension or stress transferred to the lens by the suspensory ligaments. This results in increased convexity of the lens which in turn increases the optical power of the eye. As humans age, the amplitude of accommodation reduces from approximately 15 to 20 dioptres in the very young, to about 10 dioptres at age 25, to around 1 dioptre at 50 and over.
Convex lenses have positive dioptric value and are generally used to correct hyperopia (farsightedness) or to allow people with presbyopia (the limited accommodation of advancing age) to read at close range. Concave lenses have negative dioptric value and generally correct myopia (nearsightedness). Typical glasses for mild myopia will have a power of −1.00 to −3.00 dioptres, while over the counter reading glasses will be rated at +1.00 to +3.00 dioptres. Optometrists usually measure refractive error using lenses graded in steps of 0.25 dioptres.
The dioptre can also be used as a measurement of curvature equal to the reciprocal of the radius measured in metres. For example, a circle with a radius of 1/2 metre has a curvature of 2 dioptres. If the curvature of a surface of a lens is C and the index of refraction is n, the focusing power is ɸ = (n − 1)C. If both surfaces of the lens are curved, consider their curvatures as positive toward the lens and add them. This will give approximately the right result, as long as the thickness of the lens is much less than the radius of curvature of one of the surfaces. For a mirror the focusing power is ɸ = 2C.
# Relation to magnifying power
The magnifying power of a simple magnifier is related to its optical power. This is covered in detail in the articles on magnification and magnifying glasses. | https://www.wikidoc.org/index.php/Diopter | |
968bb88d230cfbe8f05eb17fa175530f59bada73 | wikidoc | Diosmin | Diosmin
Diosmin is a semisynthetic phlebotropic drug, a member of the flavonoid family. It is used with Hesperidin to control internal symptoms of hemorrhoids (piles). It is an oral phlebotropic drug used in the treatment of venous disease, i.e., chronic venous insufficiency (CVI) and hemorrhoidal disease (HD), in acute or chronic hemorrhoids, in place of rubber-band ligation, in combination with fiber supplement, or as an adjuvant therapy to hemorrhoidectomy, in order to reduce secondary bleeding.
Clinical studies have been inconclusive and no review articles on its use in vascular disease have been published. It is sold in the U.S as a dietary supplement without U.S. Food and Drug Administration approval.
# Mechanisms
Diosmin prolongs the vasoconstrictor effect of noradrenaline on the vein wall, increasing venous tone, and therefore reducing venous capacitance, distensibility, and stasis. This increases the venous return and reduces venous hyperpressure present in patients suffering from CVI.
Diosmin improves lymphatic drainage by increasing the frequency and intensity of lymphatic contractions, and by increasing the total number of functional lymphatic capillaries. Furthermore, Diosmin (with Hesperidine ) decreases the diameter of lymphatic capillaries and the intralymphatic pressure.
At the microcirculation level, Diosmin reduces capillary hyperpermeability and increases capillary resistance by protecting the microcirculation from damaging processes.
Diosmin reduces the expression of endothelial adhesion molecules (ICAM1, VCAM1), and inhibits the adhesion, migration, and activation of leukocytes at the capillary level. This leads to a reduction in the release of inflammatory mediators, principally oxygen free radicals and prostaglandins (PGE2, PGF2a).
# Regulatory status
Diosmin is distributed in the U.S. by Nutratech, Inc. as a dietary supplement. The U.S. Food and Drug Administration does not approve dietary supplements, and cannot prevent a supplement from being marketed until there is strong evidence of harm. In response to Nutratech's premarket notification, the FDA concluded that there was an "inadequate basis for reasonable expectation of safety."
Nutratech argued that Diosmin has a long history of use in Europe.
Diosmin 95 is currently a prescription medication in Europe that has been used to treat Varicose and Spider veins. In May of 2006, Stragen International submitted an NDI with the FDA to market Diosmin 95 as a nutritional supplement. The NDI was approved and Diosmin 95 is now available exclusively through the Venacura brand daily supplement. () | Diosmin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]Associate Editor(s)-in-Chief: Sheng Shi, M.D. [4]
Diosmin is a semisynthetic phlebotropic drug, a member of the flavonoid family. It is used with Hesperidin to control internal symptoms of hemorrhoids (piles). It is an oral phlebotropic drug used in the treatment of venous disease, i.e., chronic venous insufficiency (CVI) and hemorrhoidal disease (HD), in acute or chronic hemorrhoids, in place of rubber-band ligation, in combination with fiber supplement, or as an adjuvant therapy to hemorrhoidectomy, in order to reduce secondary bleeding.
Clinical studies have been inconclusive and no review articles on its use in vascular disease have been published.[1][2] It is sold in the U.S as a dietary supplement without U.S. Food and Drug Administration approval.
# Mechanisms
Diosmin prolongs the vasoconstrictor effect of noradrenaline on the vein wall, increasing venous tone, and therefore reducing venous capacitance, distensibility, and stasis. This increases the venous return and reduces venous hyperpressure present in patients suffering from CVI.
Diosmin improves lymphatic drainage by increasing the frequency and intensity of lymphatic contractions, and by increasing the total number of functional lymphatic capillaries. Furthermore, Diosmin (with Hesperidine ) decreases the diameter of lymphatic capillaries and the intralymphatic pressure.
At the microcirculation level, Diosmin reduces capillary hyperpermeability and increases capillary resistance by protecting the microcirculation from damaging processes.
Diosmin reduces the expression of endothelial adhesion molecules (ICAM1, VCAM1), and inhibits the adhesion, migration, and activation of leukocytes at the capillary level. This leads to a reduction in the release of inflammatory mediators, principally oxygen free radicals and prostaglandins (PGE2, PGF2a).
# Regulatory status
Diosmin is distributed in the U.S. by Nutratech, Inc. as a dietary supplement. The U.S. Food and Drug Administration does not approve dietary supplements, and cannot prevent a supplement from being marketed until there is strong evidence of harm. In response to Nutratech's premarket notification, the FDA concluded that there was an "inadequate basis for reasonable expectation of safety."[3]
Nutratech argued that Diosmin has a long history of use in Europe.
Diosmin 95 is currently a prescription medication in Europe that has been used to treat Varicose and Spider veins. In May of 2006, Stragen International submitted an NDI with the FDA to market Diosmin 95 as a nutritional supplement. The NDI was approved and Diosmin 95 is now available exclusively through the Venacura brand daily supplement. (http://www.fda.gov/ohrms/dockets/dockets/95s0316/95s-0316-rpt0293-01-vol228.pdf) | https://www.wikidoc.org/index.php/Diosmin | |
92391e261e4085e442e3ac7def276817928765ad | wikidoc | Diploma | Diploma
A diploma (from Greek δίπλωµα diploma) is a certificate or deed issued by an educational institution, such as a university, that testifies that the recipient has successfully completed a particular course of study, or confers an academic degree. In countries such as the U.K. and Australia, the word diploma refers to a level of academic award (see below).
In some countries, such as the United Kingdom and Australia, such a document is called a testimonium or testamur, Latin for "we testify" or "certify" (testari), and so called from the word with which the certificate begins.
In Ireland it is generally called a parchment.
# Past diploma styles
Diplomas were originally made of sheepskin, as paper was not very durable and was difficult to create. The sheepskin was made paper thin and information was handwritten. Soon, parchment was used for the diploma and at the turn of the 20th century, the diploma became bound in leather.
Diplomas used to be quite large, but it has become common to print diplomas on standard letter or A4 size paper.
# As an academic award
- In the U.S., the word diploma usually refers to the actual document received at the end of higher education. It also can refer to a specific academic award. An example would be in the field of Nursing where the Diploma in Nursing was offered by hospital based schools. In other parts of the world, diploma often refers to the actual education or is some indication of the amount of time spent in study.
- In some countries, such as Australia and India a diploma is a specific academic award of lower rank than a bachelor degree (and in some areas an Advanced Diploma falls in between as well).
- In India a diploma is a specific academic award usually awarded in professional/vocational courses e.g. Engineering, Pharmacy, Designing, etc. In such cases Diploma is lower in rank than a specific bachelor degree of that discipline but equivalent to general degree in that discipline e.g. Diploma in Engineering of Electronics Engineering is lower than Bachelor of Technology in Electronics Engineering but is equivalent to Bachelor of Science in Electronics. Also Diploma are little bit specific in nature e.g. Diploma in Engineering of Electronics Engineering may be in Advanced Communication Systems (ACS) or Integrated Circuits (IC) or Industrial Electronics (IE) ...
- In Ireland a National Diploma is below the standard of the honours Bachelor's degree, whilst the Higher Diploma is taken after the bachelor degree.
- In Germany, Ukraine and other countries that adopted the German academic education system, diploma (in German Diplom) is the standard academic degree, comparable with the Bachelor's and Master's degree in one.
- In Hong Kong, higher diploma and associate degree are below the standard of the honours bachelor's degree. Certificate (not to be confused with postgraduate certificate) and diploma are below the standard of higher diploma and associate degree. Postgraduate Certificates and Postgraduate Diplomas are taken after the bachelor degree, and are more vocational oriented than a master's degree.
- In Ontario, Canada, diplomas are awarded by colleges whereas bachelor degrees are awarded by universities. In Canada there is a subtle difference between a college and a university.
- The International Baccalaureate (IB) Diploma is a pre-university qualification normally taken by students in the final two years of high school.
- In the UK, diploma can refer to several different types of academic qualification. The Diploma of Higher Education is a higher education award below the standard of a bachelor's degree. The term can also refer to a Postgraduate Diploma or to the new 14-19 Diploma to be introduced in England in September 2008. | Diploma
A diploma (from Greek δίπλωµα diploma) is a certificate or deed issued by an educational institution, such as a university, that testifies that the recipient has successfully completed a particular course of study, or confers an academic degree. In countries such as the U.K. and Australia, the word diploma refers to a level of academic award (see below).
In some countries, such as the United Kingdom and Australia, such a document is called a testimonium or testamur, Latin for "we testify" or "certify" (testari), and so called from the word with which the certificate begins.
In Ireland it is generally called a parchment.
# Past diploma styles
Diplomas were originally made of sheepskin, as paper was not very durable and was difficult to create. The sheepskin was made paper thin and information was handwritten. Soon, parchment was used for the diploma and at the turn of the 20th century, the diploma became bound in leather.
Diplomas used to be quite large, but it has become common to print diplomas on standard letter or A4 size paper.
# As an academic award
- In the U.S., the word diploma usually refers to the actual document received at the end of higher education. It also can refer to a specific academic award. An example would be in the field of Nursing where the Diploma in Nursing was offered by hospital based schools. In other parts of the world, diploma often refers to the actual education or is some indication of the amount of time spent in study.
- In some countries, such as Australia and India a diploma is a specific academic award of lower rank than a bachelor degree (and in some areas an Advanced Diploma falls in between as well).
- In India a diploma is a specific academic award usually awarded in professional/vocational courses e.g. Engineering, Pharmacy, Designing, etc. In such cases Diploma is lower in rank than a specific bachelor degree of that discipline but equivalent to general degree in that discipline e.g. Diploma in Engineering of Electronics Engineering is lower than Bachelor of Technology in Electronics Engineering but is equivalent to Bachelor of Science in Electronics. Also Diploma are little bit specific in nature e.g. Diploma in Engineering of Electronics Engineering may be in Advanced Communication Systems (ACS) or Integrated Circuits (IC) or Industrial Electronics (IE) ...
- In Ireland a National Diploma is below the standard of the honours Bachelor's degree, whilst the Higher Diploma is taken after the bachelor degree.
- In Germany, Ukraine and other countries that adopted the German academic education system, diploma (in German Diplom) is the standard academic degree, comparable with the Bachelor's and Master's degree in one.
- In Hong Kong, higher diploma and associate degree are below the standard of the honours bachelor's degree. Certificate (not to be confused with postgraduate certificate) and diploma are below the standard of higher diploma and associate degree. Postgraduate Certificates and Postgraduate Diplomas are taken after the bachelor degree, and are more vocational oriented than a master's degree.
- In Ontario, Canada, diplomas are awarded by colleges whereas bachelor degrees are awarded by universities. In Canada there is a subtle difference between a college and a university.
- The International Baccalaureate (IB) Diploma is a pre-university qualification normally taken by students in the final two years of high school.[1]
- In the UK, diploma can refer to several different types of academic qualification. The Diploma of Higher Education is a higher education award below the standard of a bachelor's degree. The term can also refer to a Postgraduate Diploma or to the new 14-19 Diploma to be introduced in England in September 2008. | https://www.wikidoc.org/index.php/Diploma | |
bb9e3fa4e0f065e1f235c1be04d0e9df64edd644 | wikidoc | Disgust | Disgust
# Overview
Disgust is an emotion that is typically associated with things that are perceived as unclean, inedible, or infectious. In The Expression of the Emotions in Man and Animals, Charles Darwin wrote that disgust refers to something revolting. Primarily in relation
to the sense of taste, as actually perceived or vividly imagined; and secondarily to anything which causes a similar feeling, through the sense of smell, touch, and even of eyesight. Disgust is one of the basic emotions of Robert Plutchik's theory of emotions. Disgust invokes a characteristic facial expression, one of Paul Ekman's six universal facial expressions of emotion. It is also associated with a fall in heart rate, in contrast, for example, to fear or anger.
Disgust may be further subdivided into physical disgust, associated with physical or metaphorical uncleanness, and moral disgust, a similar feeling related to courses of action.
# Origins and development
Disgust is thought to have its origins in (and in some cases to be identical to) instinctive reactions that evolved as part of natural selection for behavior which tended to prevent food poisoning, or exposure to danger of infection. Disgust is frequently associated with waste products such as feces or urine, secretions from the human body (such as mucus), and with decomposing flesh, and insects, such as maggots, associated with it.
As in other human instinctual drives, disgust has an instinctual and a socially constructed aspect. Psychologist Paul Rozin has studied the development of feelings of disgust in children.
Jonathan Haidt is a researcher whose work involves exploring the relationship between disgust and various traditional concepts of morality. His theory of social intuitionism seeks to explain the apparently irrational and visceral reactions to violations of the moral order.
# Disgust and shame
Martha Nussbaum, a leading American philosopher, wrote a book published in 2004 entitled Hiding From Humanity: Disgust, Shame, and the Law which examines the relationship of disgust and shame to a society's laws.
A recent study found that women and children were more sensitive to disgust than men. Researchers attempted to explain this finding in evolutionary terms. While some find wisdom in adhering to one's feelings of disgust, some scientists have asserted that "reactions of disgust are often built upon prejudices that should be challenged and rebutted."
# Brain structures
Functional MRI experiments have revealed that the anterior insula in the brain is particularly active when experiencing disgust, when being exposed to offensive tastes, and when viewing facial expressions of disgust.
# Huntington's disease
Many patients suffering from Huntington's disease, a genetically transmitted progressive neurodegenerative disease, are unable to recognize expressions of disgust in others and also don't show reactions of disgust to foul odors or tastes. The inability to recognize disgust in others appears in carriers of the Huntington gene before other symptoms appear. | Disgust
Template:Emotion
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Disgust is an emotion that is typically associated with things that are perceived as unclean, inedible, or infectious. In The Expression of the Emotions in Man and Animals, Charles Darwin wrote that disgust refers to something revolting. Primarily in relation
to the sense of taste, as actually perceived or vividly imagined; and secondarily to anything which causes a similar feeling, through the sense of smell, touch, and even of eyesight. Disgust is one of the basic emotions of Robert Plutchik's theory of emotions. Disgust invokes a characteristic facial expression, one of Paul Ekman's six universal facial expressions of emotion. It is also associated with a fall in heart rate, in contrast, for example, to fear or anger.[1]
Disgust may be further subdivided into physical disgust, associated with physical or metaphorical uncleanness, and moral disgust, a similar feeling related to courses of action.
# Origins and development
Disgust is thought to have its origins in (and in some cases to be identical to) instinctive reactions that evolved as part of natural selection for behavior which tended to prevent food poisoning, or exposure to danger of infection. Disgust is frequently associated with waste products such as feces or urine, secretions from the human body (such as mucus), and with decomposing flesh, and insects, such as maggots, associated with it.
As in other human instinctual drives, disgust has an instinctual and a socially constructed aspect. Psychologist Paul Rozin has studied the development of feelings of disgust in children.
Jonathan Haidt is a researcher whose work involves exploring the relationship between disgust and various traditional concepts of morality. His theory of social intuitionism seeks to explain the apparently irrational and visceral reactions to violations of the moral order.
# Disgust and shame
Martha Nussbaum, a leading American philosopher, wrote a book published in 2004 entitled Hiding From Humanity: Disgust, Shame, and the Law which examines the relationship of disgust and shame to a society's laws.
A recent study found that women and children were more sensitive to disgust than men. Researchers attempted to explain this finding in evolutionary terms. While some find wisdom in adhering to one's feelings of disgust, some scientists have asserted that "reactions of disgust are often built upon prejudices that should be challenged and rebutted."
# Brain structures
Functional MRI experiments have revealed that the anterior insula in the brain is particularly active when experiencing disgust, when being exposed to offensive tastes, and when viewing facial expressions of disgust.[2]
# Huntington's disease
Many patients suffering from Huntington's disease, a genetically transmitted progressive neurodegenerative disease, are unable to recognize expressions of disgust in others and also don't show reactions of disgust to foul odors or tastes.[3] The inability to recognize disgust in others appears in carriers of the Huntington gene before other symptoms appear.[4] | https://www.wikidoc.org/index.php/Disgust | |
c15d239f68787a7d9f46739538183dee0762b264 | wikidoc | Disifin | Disifin
Disifin is a brand name for a powerful disinfectant in tablet or powder. The solution is used in many areas, including hospitals, laboratories, nursing homes, funeral homes, medical, dental and veterinary facilities, and anywhere else where control of pathogens is required. It is typically used for disinfecting surfaces and soaking equipment.
Disifin has a remarkable spectrum of activity against viruses, bacteria, fungi, yeasts and spores and , including mycobacteria such as tuberculosis. It is also effective against Foot and Mouth and Avian flu.
However, for total effectiveness it must be sprayed freely on a surface and allowed to stand for at least 15 minutes before being wiped off. readily biodegradable by use of Ultraviolet(UV) light | Disifin
Disifin is a brand name for a powerful disinfectant in tablet or powder. The solution is used in many areas, including hospitals, laboratories, nursing homes, funeral homes, medical, dental and veterinary facilities, and anywhere else where control of pathogens is required. It is typically used for disinfecting surfaces and soaking equipment.
Disifin has a remarkable spectrum of activity against viruses, bacteria, fungi, yeasts and spores and , including mycobacteria such as tuberculosis. It is also effective against Foot and Mouth and Avian flu.
However, for total effectiveness it must be sprayed freely on a surface and allowed to stand for at least 15 minutes before being wiped off. readily biodegradable by use of Ultraviolet(UV) light | https://www.wikidoc.org/index.php/Disifin | |
8bf62ee51787edc23b6a401f6de3bec47f5e9a8f | wikidoc | Terpene | Terpene
# Overview
Terpenes are a large and varied class of hydrocarbons, produced primarily by a wide variety of plants, particularly conifers, though also by some insects such as swallowtail butterflies, which emit terpenes from their osmeterium. They are the major components of resin, and of turpentine produced from resin. The name "terpene" is derived from the word "turpentine".
When terpenes are modified chemically, such as by oxidation or rearrangement of the carbon skeleton, the resulting compounds are generally referred to as terpenoids. Some authors will use the term terpene to include all terpenoids.
Terpenes and terpenoids are the primary constituents of the essential oils of many types of plants and flowers. Essential oils are used widely as natural flavor additives for food, as fragrances in perfumery, and in traditional and alternative medicines such as aromatherapy. Synthetic variations and derivatives of natural terpenes and terpenoids also greatly expand the variety of aromas used in perfumery and flavors used in food additives. Vitamin A is an example of a terpene.
# Structure and biosynthesis
Terpenes are derived biosynthetically from units of isoprene, which has the molecular formula C5H8. The basic molecular formulas of terpenes are multiples of that, (C5H8)n where n is the number of linked isoprene units. This is called the isoprene rule or the C5 rule. The isoprene units may be linked together "head to tail" to form linear chains or they may be arranged to form rings. One can consider the isoprene unit as one of nature's preferred building blocks.
Isoprene itself does not undergo the building process, but rather activated forms, isopentenyl pyrophosphate (IPP or also isopentenyl diphosphate) and dimethylallyl pyrophosphate (DMAPP or also dimethylallyl diphosphate), are the components in the biosynthetic pathway. IPP is formed from acetyl-CoA via the intermediacy of mevalonic acid in the HMG-CoA reductase pathway. An alternative, totally unrelated biosynthesis pathway of IPP is known in some bacterial groups and the plastids of plants, the so-called MEP(2-Methyl-D-erythritol-4-phosphate)-pathway, which is initiated from C5-sugars. In both pathways, IPP is isomerized to DMAPP by the enzyme isopentenyl pyrophosphate isomerase.
As chains of isoprene units are built up, the resulting terpenes are classified sequentially by size as hemiterpenes, monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, and tetraterpenes.
# Types
- Hemiterpenes consist of a single isoprene unit. Isoprene itself is considered the only hemiterpene, but oxygen-containing derivatives such as prenol and isovaleric acid are hemiterpenoids.
- Monoterpenes consist of two isoprene units and have the molecular formula C10H16. Examples of monoterpenes are: geraniol, limonene and terpineol.
- Sesquiterpenes consist of three isoprene units and have the molecular formula C15H24. Examples of sesquiterpenes are: farnesol. The sesqui- prefix means one and a half.
- Diterpenes are composed for four isoprene units and have the molecular formula C20H32. They derive from geranylgeranyl pyrophosphate. Examples of diterpenes are cafestol, kahweol, cembrene and taxadiene (precursor of taxol). Diterpenes also form the basis for biologically important compounds such as retinol, retinal, and phytol.
- Sesterterpenes, terpenes having 25 carbons and five isoprene units, are rare relative to the other sizes. The sester- prefix means half to three, i.e. two and a half.
- Triterpenes consist of six isoprene units and have the molecular formula C30H48. The linear triterpene squalene, the major constituent of shark liver oil, is derived from the reductive coupling of two molecules of farnesyl pyrophosphate. Squalene is then processed biosynthetically to generate either lanosterol or cycloartenol, the structural precursors to all the steroids.
- Tetraterpenes contain eight isoprene units and have the molecular formula C40H56. Biologically important tetraterpenes include the acyclic lycopene, the monocyclic gamma-carotene, and the bicyclic alpha- and beta-carotenes.
- Polyterpenes consist of long chains of many isoprene units. Natural rubber consists of polyisoprene in which the double bonds are cis. Some plants produce a polyisoprene with trans double bonds, known as gutta-percha.
# Agri-chemical use
Research into terpenes has found that many of them possess qualities that make them ideal active ingredients as part of natural agricultural pesticides.
- link | Terpene
# Overview
Terpenes are a large and varied class of hydrocarbons, produced primarily by a wide variety of plants, particularly conifers, though also by some insects such as swallowtail butterflies, which emit terpenes from their osmeterium. They are the major components of resin, and of turpentine produced from resin. The name "terpene" is derived from the word "turpentine".
When terpenes are modified chemically, such as by oxidation or rearrangement of the carbon skeleton, the resulting compounds are generally referred to as terpenoids. Some authors will use the term terpene to include all terpenoids.
Terpenes and terpenoids are the primary constituents of the essential oils of many types of plants and flowers. Essential oils are used widely as natural flavor additives for food, as fragrances in perfumery, and in traditional and alternative medicines such as aromatherapy. Synthetic variations and derivatives of natural terpenes and terpenoids also greatly expand the variety of aromas used in perfumery and flavors used in food additives. Vitamin A is an example of a terpene.
# Structure and biosynthesis
Terpenes are derived biosynthetically from units of isoprene, which has the molecular formula C5H8. The basic molecular formulas of terpenes are multiples of that, (C5H8)n where n is the number of linked isoprene units. This is called the isoprene rule or the C5 rule. The isoprene units may be linked together "head to tail" to form linear chains or they may be arranged to form rings. One can consider the isoprene unit as one of nature's preferred building blocks.
Isoprene itself does not undergo the building process, but rather activated forms, isopentenyl pyrophosphate (IPP or also isopentenyl diphosphate) and dimethylallyl pyrophosphate (DMAPP or also dimethylallyl diphosphate), are the components in the biosynthetic pathway. IPP is formed from acetyl-CoA via the intermediacy of mevalonic acid in the HMG-CoA reductase pathway. An alternative, totally unrelated biosynthesis pathway of IPP is known in some bacterial groups and the plastids of plants, the so-called MEP(2-Methyl-D-erythritol-4-phosphate)-pathway, which is initiated from C5-sugars. In both pathways, IPP is isomerized to DMAPP by the enzyme isopentenyl pyrophosphate isomerase.
As chains of isoprene units are built up, the resulting terpenes are classified sequentially by size as hemiterpenes, monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, and tetraterpenes.
# Types
- Hemiterpenes consist of a single isoprene unit. Isoprene itself is considered the only hemiterpene, but oxygen-containing derivatives such as prenol and isovaleric acid are hemiterpenoids.
- Monoterpenes consist of two isoprene units and have the molecular formula C10H16. Examples of monoterpenes are: geraniol, limonene and terpineol.
- Sesquiterpenes consist of three isoprene units and have the molecular formula C15H24. Examples of sesquiterpenes are: farnesol. The sesqui- prefix means one and a half.
- Diterpenes are composed for four isoprene units and have the molecular formula C20H32. They derive from geranylgeranyl pyrophosphate. Examples of diterpenes are cafestol, kahweol, cembrene and taxadiene (precursor of taxol). Diterpenes also form the basis for biologically important compounds such as retinol, retinal, and phytol.
- Sesterterpenes, terpenes having 25 carbons and five isoprene units, are rare relative to the other sizes. The sester- prefix means half to three, i.e. two and a half.
- Triterpenes consist of six isoprene units and have the molecular formula C30H48. The linear triterpene squalene, the major constituent of shark liver oil, is derived from the reductive coupling of two molecules of farnesyl pyrophosphate. Squalene is then processed biosynthetically to generate either lanosterol or cycloartenol, the structural precursors to all the steroids.
- Tetraterpenes contain eight isoprene units and have the molecular formula C40H56. Biologically important tetraterpenes include the acyclic lycopene, the monocyclic gamma-carotene, and the bicyclic alpha- and beta-carotenes.
- Polyterpenes consist of long chains of many isoprene units. Natural rubber consists of polyisoprene in which the double bonds are cis. Some plants produce a polyisoprene with trans double bonds, known as gutta-percha.
# Agri-chemical use
Research into terpenes has found that many of them possess qualities that make them ideal active ingredients as part of natural agricultural pesticides.
- link
# External links
- Institute of Chemistry - terpenes
- Structures of alpha pinene and beta pinene
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c9009751479418a5fd01f818b738f1bfc7e4e397 | wikidoc | Dock180 | Dock180
Dock180, (Dedicator of cytokinesis) also known as DOCK1, is a large (~180 kDa) protein involved in intracellular signalling networks. It is the mammalian ortholog of the C. elegans protein CED-5 and belongs to the DOCK family of Guanine nucleotide exchange factors (GEFs).
# Discovery
Dock180 was identified, using a far-western blotting approach, as a binding partner of the adaptor protein Crk that was able to induce morphological changes in 3T3 fibroblasts. Subsequently it was reported that Dock180 was able to activate the small GTP-binding protein (G protein) Rac1 and this was later shown to happen via its ability to act as a GEF.
# Structure and function
Dock180 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins. In their resting state G proteins are bound to Guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphosphate (GTP). GEFs activate G proteins by promoting this nucleotide exchange.
Dock180 and related proteins differ from other GEFs in that they do not possess the canonical structure of tandem DH-PH domains known to elicit nucleotide exchange. Instead they possess a DHR2 domain which mediates Rac activation by stabilising it in its nucleotide-free state. Dock180-related proteins also possess a DHR1 domain which has been shown, in vitro, to bind phospholipids and which may be involved in their interaction with cellular membranes. Other structural features of Dock180 include an N-terminal SH3 domain involved in binding to ELMO proteins (see below) and a C-terminal proline-rich region which, in Myoblast city (the Drosophila melanogaster ortholog of Dock180), was shown to bind DCrk (the Drosophila ortholog of Crk).
# Regulation of Dock180 Activity
Under physiological conditions Dock180 alone is inefficient at promoting nucleotide exchange on Rac. Effective GEF activity requires an interaction between Dock180 and its binding partner ELMO. ELMO1 is the most comprehensively described isoform of this small family of non-catalytically active proteins which function to recruit Dock180 to the plasma membrane and induce conformational changes which increase GEF efficiency. ELMO1 has also been reported to inhibit ubiqitinylation of Dock180 and so prevent its degradation by proteasomes. Receptor-mediated activation of RhoG (a small G protein of the Rac subfamily) is perhaps the best known inducer of Dock180 GEF activity. Active (GTP-bound) RhoG recruits the ELMO/Dock180 complex to the plasma membrane thereby bringing Dock180 into contact with its substrate, Rac. In tumour cells Dock180 is regulated by a complex containing Crk and p130Cas which is in turn regulated by cooperative signalling by β3-containing integrin complexes and the membrane-bound protein uPAR.
# Signalling Downstream of Dock180
Dock180 is a Rac-specific GEF and so is responsible for a subset of Rac-specific signalling events. These include cell migration and phagocytosis of apoptotic cells in C. elegans, neurite outgrowth in PC12 cells and myoblast fusion in the Zebrafish embryo. More recently the DHR1 domain of Dock180 was shown to bind SNX5 (a sorting nexin) and this interaction promoted retrograde transport of the cation-independent mannose 6-phosphate receptor to the Trans-Golgi Network in a Rac-independent manner. Increased expression of Dock180 and Elmo has been reported to contribute to glioma invasion.
# Interactions
Dock180 has been shown to interact with:
- BCAR1,
- CRK
- ELMO1, and
- Grb2. | Dock180
Dock180, (Dedicator of cytokinesis) also known as DOCK1, is a large (~180 kDa) protein involved in intracellular signalling networks.[1] It is the mammalian ortholog of the C. elegans protein CED-5 and belongs to the DOCK family of Guanine nucleotide exchange factors (GEFs).[2]
# Discovery
Dock180 was identified, using a far-western blotting approach, as a binding partner of the adaptor protein Crk that was able to induce morphological changes in 3T3 fibroblasts.[3] Subsequently it was reported that Dock180 was able to activate the small GTP-binding protein (G protein) Rac1[4] and this was later shown to happen via its ability to act as a GEF.[5]
# Structure and function
Dock180 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins. In their resting state G proteins are bound to Guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphosphate (GTP). GEFs activate G proteins by promoting this nucleotide exchange.
Dock180 and related proteins differ from other GEFs in that they do not possess the canonical structure of tandem DH-PH domains known to elicit nucleotide exchange. Instead they possess a DHR2 domain which mediates Rac activation by stabilising it in its nucleotide-free state.[5] Dock180-related proteins also possess a DHR1 domain which has been shown, in vitro, to bind phospholipids[6] and which may be involved in their interaction with cellular membranes. Other structural features of Dock180 include an N-terminal SH3 domain involved in binding to ELMO proteins (see below)[7] and a C-terminal proline-rich region which, in Myoblast city (the Drosophila melanogaster ortholog of Dock180), was shown to bind DCrk (the Drosophila ortholog of Crk).[8]
# Regulation of Dock180 Activity
Under physiological conditions Dock180 alone is inefficient at promoting nucleotide exchange on Rac.[7] Effective GEF activity requires an interaction between Dock180 and its binding partner ELMO. ELMO1 is the most comprehensively described isoform of this small family of non-catalytically active proteins which function to recruit Dock180 to the plasma membrane and induce conformational changes which increase GEF efficiency.[9][10][11] ELMO1 has also been reported to inhibit ubiqitinylation of Dock180 and so prevent its degradation by proteasomes.[12] Receptor-mediated activation of RhoG (a small G protein of the Rac subfamily) is perhaps the best known inducer of Dock180 GEF activity. Active (GTP-bound) RhoG recruits the ELMO/Dock180 complex to the plasma membrane thereby bringing Dock180 into contact with its substrate, Rac.[13] In tumour cells Dock180 is regulated by a complex containing Crk and p130Cas which is in turn regulated by cooperative signalling by β3-containing integrin complexes and the membrane-bound protein uPAR.[14]
# Signalling Downstream of Dock180
Dock180 is a Rac-specific GEF and so is responsible for a subset of Rac-specific signalling events. These include cell migration and phagocytosis of apoptotic cells in C. elegans,[15] neurite outgrowth in PC12 cells[16] and myoblast fusion in the Zebrafish embryo.[17] More recently the DHR1 domain of Dock180 was shown to bind SNX5 (a sorting nexin) and this interaction promoted retrograde transport of the cation-independent mannose 6-phosphate receptor to the Trans-Golgi Network in a Rac-independent manner.[18] Increased expression of Dock180 and Elmo has been reported to contribute to glioma invasion.[19]
# Interactions
Dock180 has been shown to interact with:
- BCAR1,[20]
- CRK[20][21][22][23][24]
- ELMO1,[25][26] and
- Grb2.[20][21] | https://www.wikidoc.org/index.php/Dock180 | |
eed3ded31ce8ac385392ba4dadf5be3e16a18a83 | wikidoc | Doctors | Doctors
Doctor (gen.: doctoris) means teacher in Latin and is a contraction of the Greek διδάκτωρ, didaktōr, teacher, from the verb διδάσκειν, didaskein, to teach. It has been used continuously as an honored academic title for over a millennium in Europe, where it dates back to the rise of the university. This use spread to the Americas, former European colonies, and is now prevalent in most of the world. As a prefix — abbreviated "Dr"— its primary designation is a person who has obtained a doctorate (that is, a doctoral degree), which is the highest rank of academic degree awardable. Doctoral degrees may be "research doctorates", awarded on the basis of competency in research, or "taught doctorates" (also called "professional doctorates", because they are invariably awarded in professional subjects), awarded on the basis of coursework and adjunct requirements (if any) successfully completed by the conferee.
In some languages, when addressing several persons of whom each holds a doctor title, one can use the plural abbreviation Dres. (for Latin 'doctores'). E.g., instead of Dr. Miller and Dr. Rubinstein: Dres. Miller and Rubinstein. In English the alternative "Drs." can be used. In the present-day United Kingdom, it would be very unusual - and considered slightly facetious - to address people in this way unless they were business partners; practice elswhere in the world may be different.
# Doctor as a noun
Throughout most of the academic world, the term "doctor" refers to an individual who earned a degree such as the Doctor of Medicine, or M.D. (an abbreviation of the Latin Medicinæ Doctor) or Doctor of Philosophy, or Ph.D. (an abbreviation for the Latin Philosophiæ Doctor; or alternatively Doctor philosophiæ, D.Phil., originally from the Greek Διδάκτωρ Φιλοσοφίας, Didaktōr Philosophias, meaning Teacher of Philosophy).
The first academic degrees were all law degrees, and the first law degrees were doctorates. The origins of the doctorate dates back to the ijazat attadris wa 'l-ifttd ("license to teach and issue legal opinions") in the medieval Islamic madrasahs. The foundations of the first universities in Europe were the glossators of the 11th century, which were schools of law. The first European university, that of Bologna, was founded as a school of law by four famous legal scholars in the 12th century who were students of the glossator school in that city. It is from this history that it is said that the first academic title of doctor applied to scholars of law. The degree and title were not applied to scholars of other disciplines until the 13th century. And at the University of Bologna from its founding in the 12th century until the end of the 20th century the only degree conferred was the doctorate, usually earned after five years of intensive study after secondary school. The rising of the doctor of philosophy to its present level is a modern novelty. At its origins, a doctorate was simply a qualification for a guild—that of teaching law.
The earliest doctoral degrees (theology, philosophy, law, and medicine) reflected the historical separation of all university study into these three fields. Over time the D.D. has gradually become less common and studies outside theology and medicine have become more common (such studies were then called "philosophy", but are now classified as sciences and humanities - however this usage survives in the degree of Doctor of Philosophy).
The Ph.D. was originally a degree granted by a university to learned individuals who had achieved the approval of their peers and who had demonstrated a long and productive career in the field of philosophy. The appellation of "Doctor" (from Latin: teacher) was usually awarded only when the individual was in middle age. It indicated a life dedicated to learning, to knowledge, and to the spread of knowledge.
The Ph.D. entered widespread use in the 19th century at the Friedrich Wilhelm University in Berlin as a degree to be granted to someone who had undertaken original research in the sciences or humanities. From there it spread to the United States, arriving at Yale University in 1861, and then to the United Kingdom in 1921. This displaced the existing Doctor of Philosophy degree in some Universities; for instance, the D.Phil. (higher doctorate in the faculty of philosophy) at the University of St Andrews was discontinued and replaced with the Ph.D. (research doctorate). However, some UK universities such as Oxford and Sussex (and, until recently, York) retain the D.Phil. appellation for their research degrees, as does the University of Waikato in New Zealand.
In the US, the Sc. D., which was first conferred in North America by Harvard in 1872, is rarer than the Ph.D. However, the Sc.D. degree has long been awarded by leading institutions such as Harvard University, Johns Hopkins University, Massachusetts Institute of Technology, Washington University in St. Louis, etc. At many of these universities, the academic requirements for the Ph.D. and Sc.D. are identical.
Some ability to carry out original research must be documented by producing a dissertation or thesis, often of substantial length. The degree and title "doctor" is often a prerequisite for permanent (or nearly permanent) employment as a university lecturer or as a researcher in some sciences, though this varies on a regional basis. In others such as engineering or geology, a doctoral degree is considered desirable but not essential for employment. In a small but growing number of fields, the doctorate is felt to injure employment prospects by causing 'overqualification' for the job.
## Medical profession
In English-speaking countries, the title doctor is strongly associated with the medical profession. Most medical practitioners use the title professionally and socially.
- In the United Kingdom and many Commonwealth countries, those training for the medical profession take a five or six year course leading to the degrees of Bachelor of Medicine and Bachelor of Surgery (MBBS and similar abbreviations); the higher postgraduate degree of Doctor of Medicine (MD) is reserved for those who can prove a particular distinction on the field, usually through a body of published work or the submission of a dissertation. In guidance issued by Who's Who publisher A & C Black, it is noted that in the context of the United Kingdom, "not all qualified medical hold the degree" but that "those ... who have not taken are addressed as if they had."
- A & C Black also note that British surgeons - a designation reserved for those who have obtained fellowships of the Royal College of Surgeons - are addressed as Mr, Mrs or Miss rather than Dr. This custom has been commented on in the British Medical Journal and may stem from the historical origins of the profession.
- For many years the UK's General Dental Council (GDC) regarded the use of the title doctor by dentists as a disciplinary offence; however on November 14, 1995 the GDC ruled that dentists could use the title doctor thenceforth provided that they did not do so to imply that they held qualifications that they did not possess.
- Speaking in the House of Commons of the United Kingdom on January 19, 1996, health minister Gerald Malone noted that the title doctor had never been restricted to either medical practitioners or those with doctoral degrees in the United Kingdom, commenting that the word was defined by common usage but that the titles "physician, doctor of medicine, licentiate in medicine and surgery, bachelor of medicine, surgeon, general practitioner and apothecary" did have special protection in law.
- In the United States and other countries, the basic medical qualification is the M.D. degree, usually taken following a Bachelor of Science (B.S.) degree. In terms of course content and learning outcomes, the United States M.D. is broadly the same as the British MBBS qualifications. Other health-related disciplines such as dentistry use a similar educational framework.
In German-speaking countries the word Doktor refers exclusively to someone with a research doctorate, and is distinct from Arzt, which refers exclusively to a medical practitioner. An Arzt who holds the Dr. med. degree is addressed as Herr Doktor; an Artz who does not would simply be Herr.
## Legal profession
Academically, law is a doctoral subject in certain countries, the United States and most European countries among them. Centuries ago, lawyers were called "civil doctors" as distinct from the medical doctor and other types.
In the United States, while some lawyers do use the title "Dr.", practising lawyers are typically called "Mr." or "Ms./Mrs./Miss", regardless of whether they possess a Juris Doctor degree or not. This is a convention of the courts, of litigation and of the legal profession generally. The title Counselor is often used in courtrooms in the United States. A judge or justice in the United States is addressed as Judge followed by his or her surname outside the court room. In the court room, he or she is addressed as "your honor". Practicing lawyers usually are not addressed as "Doctor". An exception is when a lawyer with a doctoral degree is a witness in a proceeding, in which case that person may be addressed "Doctor" in the witness box.
In other countries such as Portugal, and in most South American countries (Brazil, Argentina, Colombia, Peru, and Uruguay), practising lawyers are called "Doctor". In France, Belgium and Quebec, it is common to use the title "Maître" (literally meaning Master and abbreviated Me). (In Quebec, the title Maître is used in English as well as French.)
Historically, U.S. legal education followed the British model. Law was an undergraduate subject and a degree in law was an undergraduate degree, typically the Legum Baccalaureus (LL.B.) or Bachelor of Laws. This was the basic qualifying degree. People who wanted to teach in law school, or who wished to add to their knowledge after a few years of practice, would go on from the LL.B. to take the Legum Magister (LL.M.) or Master of Laws. The terminal degree in the sequence was the LL.D. or Doctor of Laws. This represents the top law degree in The United Kingdom, Ireland, and throughout the Commonwealth. In the United States however, a course of events led to the LL.D. becoming a merely honorary degree, while law was elevated to a graduate program and its degrees graduate-level degrees. In the USA, unlike the UK and in the Commonwealth generally, all LL.D. degrees are conferred honoris causa as an honorary degree to people of distinction in public life. There is no course of study leading to this degree.
In most cases, an undergraduate degree in the United States is considered a basic foundation in academia, not a professional degree. Engineering is an exception. Nevertheless, as a general rule, an academic program requiring that the applicant earn an undergraduate degree prior to application for admission is considered a graduate program, and the degree conferred after completing that program is considered a graduate degree. The LL.B. degree, as a Bachelor's degree, is an undergraduate degree equal to a Bachelor of Arts or a Bachelor of Science. The Juris Doctor degree became the standard legal degree, to reflect both the graduate nature of the training, and a professional standing.
By World War I, students had to complete two years or 60 credits of undergraduate coursework before admission to law school, this is still the rule enshrined in law in the State of California, though ABA-accredited law schools in the state exceed this minimum standard. Most ABA-accredited law schools require completion of a bachelor's degree for admission to a J.D. or D.Jur. program.
By 1971, the J.D. degree had completely replaced the LL.B. in the American law school. Some schools also issue graduate degrees in law in programs not meant to train lawyers. Loyola University of Chicago, for example, offers a Juris Magister or Master of Jurisprudence degree in health law, for health law professionals who require a working knowledge of law (e.g., to communicate intelligently with attorneys) but do not need to become attorneys.
The LL.M. is a post-J.D. degree and exists as a specialty for practicing tax, environment, or other specialized areas in American law. It also exists as a special case in American legal tradition, as a conversion or adaptation of foreign legal training into qualifications to practice in the United States. Many states, for example, will accept a foreign law degree as a qualification for admission to practice if the degree is supplemented by an LL.M. degree from an American law school. A few American law schools do not offer any LL.M. programs except LL.M. programmes for foreign-trained students.
Some U.S. law schools offer explicitly post-J.D./LL.M. law programmes with the creation of the Scientiae Juris Doctor or S.J.D. degree (Doctor of the Science of Law) (J.S.D. is also used). Like the Ph.D., the S.J.D requires scholarly research and the successful completion of a dissertation.
It is interesting to note than in the ABA Journal, November 2006, an article titled "Lawyers Are Doctors, Too" addresses the question of whether or not an attorney in the United States can call him/herself Doctor. In essence ABA Informal Opinion 1152 (1970) allows those who hold a Juris Doctor (J.D.) to use the title doctor (the article also clarified this right for holders of the LL.M. (Mastsers of Law), but only in the context of such an individual already retaining a J.D. degree (YourABA, September 2007, quoting Informal Opinion 1152.) See also ABA Model Code of Professional Responsibility, Disciplinary Rule 2-102(E). Under prior ethical rules, the use of the title doctor was prohibited as being self-laudation. Some states prohibit attorneys from using the title doctor without clarification since it might mislead the public into thinking the attorney is a health professional. In all states attorneys must avoid using the title doctor in a manner that might mislead the public, such as advertising where a medical malpractice attorney uses "Doctor" in a manner which could cause the public to believe the attorney is a medical professional with relevant medical experience.
In Germany, about one in eight lawyers has a doctoral degree and most qualify via two state exams which entitle them to be recognised by a chamber (Anwaltskammer) as legal practitioners. A Doctor of Law was historically accorded the same privileges as a baron (including, for example, the privilege of being allowed to use the same hawk as a baron).
# Use of "doctor" as a title of address
Those who possess a doctoral degree are generally entitled to call themselves "Doctor", although restrictions apply in some jurisdictions and some situations (e.g., when it would mislead someone to think that they are licensed physician). Dentists, optometrists, podiatrists, and veterinarians are often called "doctor" as well.
In the United Kingdom, South Africa, Australia, New Zealand, Canada and other areas whose culture was recently linked to the United Kingdom, the title Doctor generally applies in both the academic and clinical fields. "Registered medical practitioners" usually do not have a doctorate; rather, they have the degree of Bachelor of Medicine (usually also with surgery). Cultural conventions exist, clinicians who are Members or Fellows of the Royal College of Surgeons are an exception. As a homage to their predecessors, the barber surgeons, they prefer to be addressed as Mr, Mrs, Ms or Miss, even if they do hold a doctorate. When a medically-qualified person passes the notoriously difficult examinations which enable them to become a member of one or more of the Royal Surgical Colleges and become "MRCS", it is customary for them to drop the "Doctor" prefix and take up "Mister". This rule applies to any doctor of any grade who has passed the appropriate exams, and is not the exclusive province of consultant-level surgeons. In recent times, other surgically-orientated specialists, such as gynaecologists, have also adopted the "Mister" prefix. A surgeon who is also a professor is usually known as "Professor" and, similarly, a surgeon who has been enobled, knighted, created a baronet or appointed a dame uses the corresonding title (Lord, Sir, Dame). Physicians, on the other hand, when they pass their "MRCP" examinations, which enable them to become members of the Royal College of Physicians, do not drop the "Doctor" prefix and remain doctor, even when they are consultants. In the United Kingdom the status and rank of consultant surgeons with the MRCS, titled "mister", and consultant physicians with the MRCP, titled "doctor", is identical. Surgeons in the USA and elsewhere may have the title "doctor".
In Italy, all university graduates (after a 3 year course equivalent to a Bachelor degree) receive the title "Dottore"; after earning a second 2-years degree "Dottore Magistrale", and after earning their Ph.D. "Dottore di Ricerca". Therefore, Italians thus address each other and present themselves as "Dott." or Dr. even if not holding what in other countries is considered a doctorate. This phenomenon may have been caused by Italy's previous lack of a "Ph.D." degree.
In German speaking countries, all holders of doctorate degrees are appropriately addressed as "Dr X" in all social situations. However, those granted PhDs from other countries may find themselves in legal difficulties if they use the term "Doktor" professionally in Germany.
In the Philippines, where titles and names of occupations usually follow Spanish naming conventions (gender-specific terms), the feminine form of "Doktor" is "Doktora", and is abbreviated usually as "Dra."
Many academic, research scientist and practitioners in subjects allied to medicine also use Dr and/or their terminal degree after their last name. (Terminal degrees include Ph.D., Sc.D., Ed.D., or Psy.D.)
EU legislation recognises academic qualifications (including higher degrees and doctorates) of all member states. In Germany, a recent federal law (signed by all Cultural and Educational Ministers in accord with the EU law) confirmed the standardisation of qualifications and recognised that non-Germans were also entitled to use the title Doctor if they possessed an equivalent and recognised qualification from an EU member state. Until this Federal Law was introduced, there was no recognised mechanism to prevent administrators in private bodies and civil servants in public-funded bodies (such as universities) from automatically discriminating between the qualifications of people with German doctorates compared to holders of doctorates from an EU member state. The German university bureaucratic practice of using the post-nominal form, "Ph.D." (or equivalent), to distinguish non-German doctorates can be challenged legally as evidence of arbitrary discrimination and prejudice against non-German nationals (academics). All EU citizens are now "legally entitled" to use and be titled (addressed) as "Doctor" or "Dr." in all formal, legal and published communications. For academics with doctorates from non-EU member states, the qualification must be recognised formally ("validated") by the Federal Educational Ministry in Bonn. The recognition process can be done by the employer or employee and may be part of the official bureaucracy for confirming professional status and is dependent on individual bilateral agreements between Germany and other countries.
In Hungary the title of Doctor used to become a part of the name and is added as such to personal ID documents. The use of this practice has been significantly declined in the recent years, although legally it is still possible.
## Correct abbreviation of "Doctor"
The switch from "Doctor" to its abbreviated form involves contraction rather than truncation. In British English it is not necessary to indicate a contraction with a full stop (period) after the abbreviation, while the opposite holds true in North American English. This means that while the abbreviation of Doctor is usually written as "Dr" in most of the Commonwealth, it is usually written as "Dr." in North America.
Similarly, conventions regarding the punctuation of degree abbreviations vary. In the United Kingdom, it is increasingly common to omit punctuations from abbreviations that are not truncations: while the usual abbreviation of "Esquire" is "Esq.", the usual abbreviation for "Doctor of Philosophy" is "PhD". It is not incorrect to use the fully-punctuated "Ph.D.", though if this pattern is used, it should be used consistently; practice in particular situations may vary, and it is always more correct to be consistent with a local patterns of usage than to deviate from it.
# Honorary doctorates
An honorary doctorate is a doctoral degree awarded for service to the institution or the wider community. This service does not need be academic in nature. Often, the same set of degrees is used as for higher doctorates, but they are distinguished as being honoris causa: in comprehensive lists, the lettering used to indicate the possession of a higher doctorate is often adjusted to indicate this, e.g. "Hon. Sc.D." rather than "Sc.D". The degree of Doctor of the University (D.Univ.) however is only awarded as an honorary degree.
Who's Who publishers A & C Black note that honorary doctorates are not used in circumstances where they might be taken to imply an academic qualification and advises following the holder's preference when determining whether to address an "honorary" doctor as "Dr."
# Other uses of "Doctor"
- In some regions, such as the American South, "Doctor" is traditionally added to the first name of people (especially men) holding doctorates, where it is used in either direct or indirect familiar address.
- "Doc" is a common nickname or for someone with a doctoral degree, in real life and in fiction — for example, the character "Doc" in Gunsmoke and Doc Holliday. Also, Doc Savage, 'Man of Bronze', a series of young adult pulp fiction paperback books popular among US high school students during the 1960s and 1970s. "Doc" is Marty McFly's nickname for Doctor Emmett Brown in the Back to the Future trilogy.
- In Roman Catholicism and several other Christian denominations, a Doctor of the Church is an eminent theologian (e.g. Thomas Aquinas, also known as the Angelic Doctor) from whose teachings the whole Church is held to have derived great advantage. | Doctors
Doctor (gen.: doctoris) means teacher in Latin and is a contraction of the Greek διδάκτωρ, didaktōr, teacher, from the verb διδάσκειν, didaskein, to teach. It has been used continuously as an honored academic title for over a millennium in Europe, where it dates back to the rise of the university. This use spread to the Americas, former European colonies, and is now prevalent in most of the world. As a prefix — abbreviated "Dr"— its primary designation is a person who has obtained a doctorate (that is, a doctoral degree), which is the highest rank of academic degree awardable. Doctoral degrees may be "research doctorates", awarded on the basis of competency in research, or "taught doctorates" (also called "professional doctorates", because they are invariably awarded in professional subjects), awarded on the basis of coursework and adjunct requirements (if any) successfully completed by the conferee.
In some languages, when addressing several persons of whom each holds a doctor title, one can use the plural abbreviation Dres. (for Latin 'doctores'). E.g., instead of Dr. Miller and Dr. Rubinstein: Dres. Miller and Rubinstein. In English the alternative "Drs." can be used. In the present-day United Kingdom, it would be very unusual - and considered slightly facetious - to address people in this way unless they were business partners; practice elswhere in the world may be different.
# Doctor as a noun
Throughout most of the academic world, the term "doctor" refers to an individual who earned a degree such as the Doctor of Medicine, or M.D. (an abbreviation of the Latin Medicinæ Doctor) or Doctor of Philosophy, or Ph.D. (an abbreviation for the Latin Philosophiæ Doctor; or alternatively Doctor philosophiæ, D.Phil., originally from the Greek Διδάκτωρ Φιλοσοφίας, Didaktōr Philosophias, meaning Teacher of Philosophy).
The first academic degrees were all law degrees, and the first law degrees were doctorates. The origins of the doctorate dates back to the ijazat attadris wa 'l-ifttd ("license to teach and issue legal opinions") in the medieval Islamic madrasahs.[1] The foundations of the first universities in Europe were the glossators of the 11th century, which were schools of law. [2] The first European university, that of Bologna, was founded as a school of law by four famous legal scholars in the 12th century who were students of the glossator school in that city. It is from this history that it is said that the first academic title of doctor applied to scholars of law. The degree and title were not applied to scholars of other disciplines until the 13th century.[3] And at the University of Bologna from its founding in the 12th century until the end of the 20th century the only degree conferred was the doctorate, usually earned after five years of intensive study after secondary school. The rising of the doctor of philosophy to its present level is a modern novelty.[4] At its origins, a doctorate was simply a qualification for a guild—that of teaching law.[5]
The earliest doctoral degrees (theology, philosophy, law, and medicine) reflected the historical separation of all university study into these three fields. Over time the D.D. has gradually become less common and studies outside theology and medicine have become more common (such studies were then called "philosophy", but are now classified as sciences and humanities - however this usage survives in the degree of Doctor of Philosophy).
The Ph.D. was originally a degree granted by a university to learned individuals who had achieved the approval of their peers and who had demonstrated a long and productive career in the field of philosophy. The appellation of "Doctor" (from Latin: teacher) was usually awarded only when the individual was in middle age. It indicated a life dedicated to learning, to knowledge, and to the spread of knowledge.
The Ph.D. entered widespread use in the 19th century at the Friedrich Wilhelm University in Berlin as a degree to be granted to someone who had undertaken original research in the sciences or humanities. From there it spread to the United States, arriving at Yale University in 1861, and then to the United Kingdom in 1921. This displaced the existing Doctor of Philosophy degree in some Universities; for instance, the D.Phil. (higher doctorate in the faculty of philosophy) at the University of St Andrews was discontinued and replaced with the Ph.D. (research doctorate). However, some UK universities such as Oxford and Sussex (and, until recently, York) retain the D.Phil. appellation for their research degrees, as does the University of Waikato in New Zealand.
In the US, the Sc. D., which was first conferred in North America by Harvard in 1872, is rarer than the Ph.D. However, the Sc.D. degree has long been awarded by leading institutions such as Harvard University, Johns Hopkins University, Massachusetts Institute of Technology, Washington University in St. Louis, etc. At many of these universities, the academic requirements for the Ph.D. and Sc.D. are identical.
Some ability to carry out original research must be documented by producing a dissertation or thesis, often of substantial length. The degree and title "doctor" is often a prerequisite for permanent (or nearly permanent) employment as a university lecturer or as a researcher in some sciences, though this varies on a regional basis. In others such as engineering or geology, a doctoral degree is considered desirable but not essential for employment. In a small but growing number of fields, the doctorate is felt to injure employment prospects by causing 'overqualification' for the job.
## Medical profession
In English-speaking countries, the title doctor is strongly associated with the medical profession. Most medical practitioners use the title professionally and socially.
- In the United Kingdom and many Commonwealth countries, those training for the medical profession take a five or six year course leading to the degrees of Bachelor of Medicine and Bachelor of Surgery (MBBS and similar abbreviations);[6] the higher postgraduate degree of Doctor of Medicine (MD) is reserved for those who can prove a particular distinction on the field, usually through a body of published work or the submission of a dissertation.[7] In guidance issued by Who's Who publisher A & C Black,[8] it is noted that in the context of the United Kingdom, "not all qualified medical [practitioners] hold the [MD] degree" but that "those ... who have not taken [it] are addressed as if they had."
- A & C Black also note that British surgeons - a designation reserved for those who have obtained fellowships of the Royal College of Surgeons - are addressed as Mr, Mrs or Miss rather than Dr. This custom has been commented on in the British Medical Journal and may stem from the historical origins of the profession.[9]
- For many years the UK's General Dental Council (GDC) regarded the use of the title doctor by dentists as a disciplinary offence; however on November 14, 1995 the GDC ruled that dentists could use the title doctor thenceforth provided that they did not do so to imply that they held qualifications that they did not possess.[10]
- Speaking in the House of Commons of the United Kingdom on January 19, 1996, health minister Gerald Malone noted that the title doctor had never been restricted to either medical practitioners or those with doctoral degrees in the United Kingdom, commenting that the word was defined by common usage but that the titles "physician, doctor of medicine, licentiate in medicine and surgery, bachelor of medicine, surgeon, general practitioner and apothecary" did have special protection in law.[11]
- In the United States and other countries, the basic medical qualification is the M.D. degree, usually taken following a Bachelor of Science (B.S.) degree. In terms of course content and learning outcomes, the United States M.D. is broadly the same as the British MBBS qualifications. Other health-related disciplines such as dentistry use a similar educational framework.
In German-speaking countries the word Doktor refers exclusively to someone with a research doctorate, and is distinct from Arzt, which refers exclusively to a medical practitioner. An Arzt who holds the Dr. med. degree is addressed as Herr Doktor; an Artz who does not would simply be Herr.
## Legal profession
Academically, law is a doctoral subject in certain countries, the United States and most European countries among them. Centuries ago, lawyers were called "civil doctors" as distinct from the medical doctor and other types.
In the United States, while some lawyers do use the title "Dr.", practising lawyers are typically called "Mr." or "Ms./Mrs./Miss", regardless of whether they possess a Juris Doctor degree or not. This is a convention of the courts, of litigation and of the legal profession generally. The title Counselor is often used in courtrooms in the United States. A judge or justice in the United States is addressed as Judge followed by his or her surname outside the court room. In the court room, he or she is addressed as "your honor". Practicing lawyers usually are not addressed as "Doctor". An exception is when a lawyer with a doctoral degree is a witness in a proceeding, in which case that person may be addressed "Doctor" in the witness box.
In other countries such as Portugal, and in most South American countries (Brazil, Argentina, Colombia, Peru, and Uruguay), practising lawyers are called "Doctor". In France, Belgium and Quebec, it is common to use the title "Maître" (literally meaning Master and abbreviated Me). (In Quebec, the title Maître is used in English as well as French.)
Historically, U.S. legal education followed the British model. Law was an undergraduate subject and a degree in law was an undergraduate degree, typically the Legum Baccalaureus (LL.B.) or Bachelor of Laws. This was the basic qualifying degree. People who wanted to teach in law school, or who wished to add to their knowledge after a few years of practice, would go on from the LL.B. to take the Legum Magister (LL.M.) or Master of Laws. The terminal degree in the sequence was the LL.D. or Doctor of Laws. This represents the top law degree in The United Kingdom, Ireland, and throughout the Commonwealth. In the United States however, a course of events led to the LL.D. becoming a merely honorary degree, while law was elevated to a graduate program and its degrees graduate-level degrees. In the USA, unlike the UK and in the Commonwealth generally, all LL.D. degrees are conferred honoris causa as an honorary degree to people of distinction in public life. There is no course of study leading to this degree.
In most cases, an undergraduate degree in the United States is considered a basic foundation in academia, not a professional degree. Engineering is an exception. Nevertheless, as a general rule, an academic program requiring that the applicant earn an undergraduate degree prior to application for admission is considered a graduate program, and the degree conferred after completing that program is considered a graduate degree. The LL.B. degree, as a Bachelor's degree, is an undergraduate degree equal to a Bachelor of Arts or a Bachelor of Science. The Juris Doctor degree became the standard legal degree, to reflect both the graduate nature of the training, and a professional standing.
By World War I, students had to complete two years or 60 credits of undergraduate coursework before admission to law school, this is still the rule enshrined in law in the State of California, though ABA-accredited law schools in the state exceed this minimum standard. Most ABA-accredited law schools require completion of a bachelor's degree for admission to a J.D. or D.Jur. program.
By 1971, the J.D. degree had completely replaced the LL.B. in the American law school. Some schools also issue graduate degrees in law in programs not meant to train lawyers. Loyola University of Chicago, for example, offers a Juris Magister or Master of Jurisprudence degree in health law, for health law professionals who require a working knowledge of law (e.g., to communicate intelligently with attorneys) but do not need to become attorneys.
The LL.M. is a post-J.D. degree and exists as a specialty for practicing tax, environment, or other specialized areas in American law. It also exists as a special case in American legal tradition, as a conversion or adaptation of foreign legal training into qualifications to practice in the United States. Many states, for example, will accept a foreign law degree as a qualification for admission to practice if the degree is supplemented by an LL.M. degree from an American law school. A few American law schools do not offer any LL.M. programs except LL.M. programmes for foreign-trained students.
Some U.S. law schools offer explicitly post-J.D./LL.M. law programmes with the creation of the Scientiae Juris Doctor or S.J.D. degree (Doctor of the Science of Law) (J.S.D. is also used). Like the Ph.D., the S.J.D requires scholarly research and the successful completion of a dissertation.
It is interesting to note than in the ABA Journal, November 2006, an article titled "Lawyers Are Doctors, Too" addresses the question of whether or not an attorney in the United States can call him/herself Doctor. In essence ABA Informal Opinion 1152 (1970) allows those who hold a Juris Doctor (J.D.) to use the title doctor (the article also clarified this right for holders of the LL.M. (Mastsers of Law), but only in the context of such an individual already retaining a J.D. degree (YourABA, September 2007, quoting Informal Opinion 1152.) See also ABA Model Code of Professional Responsibility, Disciplinary Rule 2-102(E). Under prior ethical rules, the use of the title doctor was prohibited as being self-laudation. Some states prohibit attorneys from using the title doctor without clarification since it might mislead the public into thinking the attorney is a health professional. In all states attorneys must avoid using the title doctor in a manner that might mislead the public, such as advertising where a medical malpractice attorney uses "Doctor" in a manner which could cause the public to believe the attorney is a medical professional with relevant medical experience.
In Germany, about one in eight lawyers has a doctoral degree and most qualify via two state exams which entitle them to be recognised by a chamber (Anwaltskammer) as legal practitioners. A Doctor of Law was historically accorded the same privileges as a baron (including, for example, the privilege of being allowed to use the same hawk as a baron).
# Use of "doctor" as a title of address
Those who possess a doctoral degree are generally entitled to call themselves "Doctor", although restrictions apply in some jurisdictions and some situations (e.g., when it would mislead someone to think that they are licensed physician). Dentists, optometrists, podiatrists, and veterinarians are often called "doctor" as well.
In the United Kingdom, South Africa, Australia, New Zealand, Canada and other areas whose culture was recently linked to the United Kingdom, the title Doctor generally applies in both the academic and clinical fields. "Registered medical practitioners" usually do not have a doctorate; rather, they have the degree of Bachelor of Medicine (usually also with surgery). Cultural conventions exist, clinicians who are Members or Fellows of the Royal College of Surgeons are an exception. As a homage to their predecessors, the barber surgeons, they prefer to be addressed as Mr, Mrs, Ms or Miss, even if they do hold a doctorate. When a medically-qualified person passes the notoriously difficult examinations which enable them to become a member of one or more of the Royal Surgical Colleges and become "MRCS", it is customary for them to drop the "Doctor" prefix and take up "Mister". This rule applies to any doctor of any grade who has passed the appropriate exams, and is not the exclusive province of consultant-level surgeons. In recent times, other surgically-orientated specialists, such as gynaecologists, have also adopted the "Mister" prefix. A surgeon who is also a professor is usually known as "Professor" and, similarly, a surgeon who has been enobled, knighted, created a baronet or appointed a dame uses the corresonding title (Lord, Sir, Dame). Physicians, on the other hand, when they pass their "MRCP" examinations, which enable them to become members of the Royal College of Physicians, do not drop the "Doctor" prefix and remain doctor, even when they are consultants. In the United Kingdom the status and rank of consultant surgeons with the MRCS, titled "mister", and consultant physicians with the MRCP, titled "doctor", is identical. Surgeons in the USA and elsewhere may have the title "doctor".
In Italy, all university graduates (after a 3 year course equivalent to a Bachelor degree) receive the title "Dottore"; after earning a second 2-years degree "Dottore Magistrale", and after earning their Ph.D. "Dottore di Ricerca". Therefore, Italians thus address each other and present themselves as "Dott." or Dr. even if not holding what in other countries is considered a doctorate. This phenomenon may have been caused by Italy's previous lack of a "Ph.D." degree.
In German speaking countries, all holders of doctorate degrees are appropriately addressed as "Dr X" in all social situations. However, those granted PhDs from other countries may find themselves in legal difficulties if they use the term "Doktor" professionally in Germany.[12]
In the Philippines, where titles and names of occupations usually follow Spanish naming conventions (gender-specific terms), the feminine form of "Doktor" is "Doktora", and is abbreviated usually as "Dra."
Many academic, research scientist and practitioners in subjects allied to medicine also use Dr and/or their terminal degree after their last name. (Terminal degrees include Ph.D., Sc.D., Ed.D., or Psy.D.)
EU legislation recognises academic qualifications (including higher degrees and doctorates) of all member states. In Germany, a recent federal law (signed by all Cultural and Educational Ministers in accord with the EU law) confirmed the standardisation of qualifications and recognised that non-Germans were also entitled to use the title Doctor if they possessed an equivalent and recognised qualification from an EU member state.[citation needed] Until this Federal Law was introduced, there was no recognised mechanism to prevent administrators in private bodies and civil servants in public-funded bodies (such as universities) from automatically discriminating between the qualifications of people with German doctorates compared to holders of doctorates from an EU member state. The German university bureaucratic practice of using the post-nominal form, "Ph.D." (or equivalent), to distinguish non-German doctorates can be challenged legally as evidence of arbitrary discrimination and prejudice against non-German nationals (academics). All EU citizens are now "legally entitled" to use and be titled (addressed) as "Doctor" or "Dr." in all formal, legal and published communications. For academics with doctorates from non-EU member states, the qualification must be recognised formally ("validated") by the Federal Educational Ministry in Bonn. The recognition process can be done by the employer or employee and may be part of the official bureaucracy for confirming professional status and is dependent on individual bilateral agreements between Germany and other countries.
In Hungary the title of Doctor used to become a part of the name and is added as such to personal ID documents. The use of this practice has been significantly declined in the recent years, although legally it is still possible.
## Correct abbreviation of "Doctor"
The switch from "Doctor" to its abbreviated form involves contraction rather than truncation. In British English it is not necessary to indicate a contraction with a full stop (period) after the abbreviation, while the opposite holds true in North American English. This means that while the abbreviation of Doctor is usually written as "Dr" in most of the Commonwealth, it is usually written as "Dr." in North America.[13]
Similarly, conventions regarding the punctuation of degree abbreviations vary. In the United Kingdom, it is increasingly common to omit punctuations from abbreviations that are not truncations: while the usual abbreviation of "Esquire" is "Esq.", the usual abbreviation for "Doctor of Philosophy" is "PhD". It is not incorrect to use the fully-punctuated "Ph.D.", though if this pattern is used, it should be used consistently; practice in particular situations may vary, and it is always more correct to be consistent with a local patterns of usage than to deviate from it.
# Honorary doctorates
An honorary doctorate is a doctoral degree awarded for service to the institution or the wider community. This service does not need be academic in nature. Often, the same set of degrees is used as for higher doctorates, but they are distinguished as being honoris causa: in comprehensive lists, the lettering used to indicate the possession of a higher doctorate is often adjusted to indicate this, e.g. "Hon. Sc.D." rather than "Sc.D". The degree of Doctor of the University (D.Univ.) however is only awarded as an honorary degree.
Who's Who publishers A & C Black note that honorary doctorates are not used in circumstances where they might be taken to imply an academic qualification and advises following the holder's preference when determining whether to address an "honorary" doctor as "Dr."[14]
# Other uses of "Doctor"
- In some regions, such as the American South, "Doctor" is traditionally added to the first name of people (especially men) holding doctorates, where it is used in either direct or indirect familiar address.
- "Doc" is a common nickname or for someone with a doctoral degree, in real life and in fiction — for example, the character "Doc" in Gunsmoke and Doc Holliday. Also, Doc Savage, 'Man of Bronze', a series of young adult pulp fiction paperback books popular among US high school students during the 1960s and 1970s. "Doc" is Marty McFly's nickname for Doctor Emmett Brown in the Back to the Future trilogy.
- In Roman Catholicism and several other Christian denominations, a Doctor of the Church is an eminent theologian (e.g. Thomas Aquinas, also known as the Angelic Doctor) from whose teachings the whole Church is held to have derived great advantage. | https://www.wikidoc.org/index.php/Doctors | |
78994ee1d9db64b2353009f5712a689fbaf4c240 | wikidoc | DrFirst | DrFirst
DrFirst is a technology company located in Rockville, Maryland. They are focused on providing systems and software to assist the Healthcare Industry. DrFirst specializes in a full-featured stand-alone electronic prescription management system. They began in 2000 with Rcopia, their first product. DrFirst’s technology keeps the Healthcare world interconnected by helping physician practices, IPAs, hospitals, health plans, pharmacies and others communicate electronically.
Rcopia and the other healthcare technology products that DrFirst has developed are designed by a management team that includes medical doctors and highly experienced technology specialists acting under the guidance and collective expertise of their Physician's Advisory Board. Utilizing the latest advancements in Internet, security, wireless, web and Personal Digital Assistant (PDA) technology, DrFirst Rcopia electronic prescribing can be interfaced with most Practice Management and Electronic Medical Records software.
DrFirst is partnered with SureScripts, RxHub, FirstDataBank, RelayHealth, Epocrates and many others, to give healthcare providers access to reliable and up to date information and services so they can better serve their patients.
Resources: DrFirst | DrFirst
DrFirst is a technology company located in Rockville, Maryland. They are focused on providing systems and software to assist the Healthcare Industry. DrFirst specializes in a full-featured stand-alone electronic prescription management system. They began in 2000 with Rcopia, their first product. DrFirst’s technology keeps the Healthcare world interconnected by helping physician practices, IPAs, hospitals, health plans, pharmacies and others communicate electronically.
Rcopia and the other healthcare technology products that DrFirst has developed are designed by a management team that includes medical doctors and highly experienced technology specialists acting under the guidance and collective expertise of their Physician's Advisory Board. Utilizing the latest advancements in Internet, security, wireless, web and Personal Digital Assistant (PDA) technology, DrFirst Rcopia electronic prescribing can be interfaced with most Practice Management and Electronic Medical Records software.
DrFirst is partnered with SureScripts, RxHub, FirstDataBank, RelayHealth, Epocrates and many others, to give healthcare providers access to reliable and up to date information and services so they can better serve their patients.
Resources: DrFirst | https://www.wikidoc.org/index.php/DrFirst | |
671ee478f726e901c390c87de13f50f9231127f8 | wikidoc | Dranath | Dranath
Dranath is a fictional herb created by author Melanie Rawn for her novels of the Dragon Prince and Dragon Star trilogies.
Grown only in the Veresch Mountains of Princemarch, the herb has several properties. When boiled, dried, and powdered, dranath can enhance the powers of a Sunrunner or sorcerer, while also helping Sunrunners cross water without illness. In this form the drug is very addicting; withdrawal will almost certainly kill the imbiber. Dranath can also cure the disease known as "The Plague", a malady which affects both humans and dragons. For non-gifted people this drug works as a hallucinogen.
# Addiction
Addiction is the strongest and most dangerous side-effect of dranath. As more of the drug is used, more of the drug is needed to satisfy the craving. Abstinance from the drug causes headaches, a swelling tongue, shaking limbs, aversion to brightness, and a chill as well as an overall ache and fatigue. In extreme cases of fighting the addiction, the victim is nearly insensible. Severe withdrawal causes unconsciousness, memory lapses, vivid and sexually explicit dreams, an itching sensation inside and out, vomiting, cramps, sweating, a foul smell, and deep, gut-twisting agony. The pain of withdrawal in these cases can drive the victim to injure him- or herself in the attempt to get more dranath or to escape the pain. If tied down, the victim's flailing might pull his/her arms from their sockets. He/She might also bite their tongue off. The culmination of all the withdrawal effects eventually weakens the body to the point of total exhaustion. At this point the heart may give out; if it does, then unless the heart restarts (often by CPR) and the victim is able to breathe, he or she will die at long last.
Too much of the drug can kill a victim just as easily as withdrawal. The imbiber feels as if they are drowning, are unable to breath, and become overwhelmed by the drug.
# Characters Associated with Dranath
- Aldiara
- Crigo
- Hollis
- Rohannon
- Roelstra
- Segev
- Sioned | Dranath
Dranath is a fictional herb created by author Melanie Rawn for her novels of the Dragon Prince and Dragon Star trilogies.
Grown only in the Veresch Mountains of Princemarch, the herb has several properties. When boiled, dried, and powdered, dranath can enhance the powers of a Sunrunner or sorcerer, while also helping Sunrunners cross water without illness. In this form the drug is very addicting; withdrawal will almost certainly kill the imbiber. Dranath can also cure the disease known as "The Plague", a malady which affects both humans and dragons. For non-gifted people this drug works as a hallucinogen.
## Addiction
Addiction is the strongest and most dangerous side-effect of dranath. As more of the drug is used, more of the drug is needed to satisfy the craving. Abstinance from the drug causes headaches, a swelling tongue, shaking limbs, aversion to brightness, and a chill as well as an overall ache and fatigue. In extreme cases of fighting the addiction, the victim is nearly insensible. Severe withdrawal causes unconsciousness, memory lapses, vivid and sexually explicit dreams, an itching sensation inside and out, vomiting, cramps, sweating, a foul smell, and deep, gut-twisting agony. The pain of withdrawal in these cases can drive the victim to injure him- or herself in the attempt to get more dranath or to escape the pain. If tied down, the victim's flailing might pull his/her arms from their sockets. He/She might also bite their tongue off. The culmination of all the withdrawal effects eventually weakens the body to the point of total exhaustion. At this point the heart may give out; if it does, then unless the heart restarts (often by CPR) and the victim is able to breathe, he or she will die at long last.
Too much of the drug can kill a victim just as easily as withdrawal. The imbiber feels as if they are drowning, are unable to breath, and become overwhelmed by the drug.
## Characters Associated with Dranath
- Aldiara
- Crigo
- Hollis
- Rohannon
- Roelstra
- Segev
- Sioned | https://www.wikidoc.org/index.php/Dranath | |
222f390eab946e127c6eabd6f7d6404117a363bd | wikidoc | Dry ice | Dry ice
Dry ice is solid carbon dioxide. It is commonly used as a versatile cooling agent.
Dry ice sublimates, changing directly to a gas at atmospheric pressure. Its sublimation and deposition point is -78.5 °C (-109.3 °F). Its enthalpy of sublimation (ΔHsub) at -78.5 °C (-109.3 °F) is 571 kJ/kg (245.5 BTU/lb). The low temperature and direct sublimation to a gas makes dry ice a very effective coolant, since it is colder than ice and leaves no moisture as it changes state. (Although it can carbonate food that is near).
# History
In 1835 the French chemist Charles Thilorier published the first account of dry ice.
Upon opening the lid of a large cylinder containing liquid carbon dioxide he noted much of the carbon dioxide rapidly evaporated leaving solid dry ice in the container. Throughout the next 60 years, dry ice was observed and tested by scientists.
# Manufacture
Dry ice is readily manufactured:
- Gases containing a high concentration of carbon dioxide are produced. Such gases can be a byproduct of some other process, such as producing ammonia and nitrogen from natural gas, or large-scale fermentation.
- Carbon dioxide-rich gas is pressurized and refrigerated until it changes into its liquid form.
- The pressure is reduced. When this occurs some liquid carbon dioxide vaporizes, and this causes a rapid lowering of temperature of the remaining liquid carbon dioxide. The extreme cold makes the liquid solidify into a snow-like consistency.
- The snow-like solid carbon dioxide is compressed into either small pellets or larger blocks of dry ice.
Dry ice is typically produced in two standard forms: blocks and cylindrical pellets. A standard block weighing approximately 30 kg is most common. These are commonly used in shipping, because they sublimate slowly due to a relatively small surface area. Pellets are around 1 cm in diameter and can be bagged easily. This form is suited to small scale use, for example at grocery stores and laboratories. Dry ice is also inexpensive; it costs less than US$2 per kilogram.
# Applications
Dry ice is commonly used to package items that need to remain cold or frozen, such as ice cream, without the use of mechanical cooling. In medicine it is used to freeze warts to make removal easier. In the construction industry it is used to loosen floor tiles by shrinking and cracking them, as well as to freeze water in valveless pipes to allow repair. In laboratories, a slurry of dry ice in an organic solvent is a useful freezing mixture for cold chemical reactions.
Dry ice can also be used for making ice cream.
Dry ice can be used in theatre productions in order to create the effect of dense fog.
Dry ice can be used to carbonate water and other liquids such as soft drink and beer. It can be used as bait to trap mosquitoes and other insects
When dry ice is placed in water sublimation is accelerated, and low-sinking dense clouds of fog (smoke like) are created. This is used in fog machines, at theaters, discoteques, Halloween, and nightclubs for dramatic effects. When used in theatre productions it creates the effect of dense fog.
Dry Ice is also used in cloud seeding: the process of altering cloud precipitation.
## Dry ice blasting
One of the largest alternative uses of dry ice is blast cleaning. Dry ice pellets are shot out of a nozzle with compressed air. This can remove residues from industrial equipment. Examples of materials being removed include ink, glue, oil, paint, mold and rubber. Dry ice blasting can replace sandblasting, steam blasting, water blasting or solvent blasting. The primary environmental residue of dry ice blasting is the sublimed CO2, thus making it a useful technique where residues from other blasting techniques are undesirable. | Dry ice
Dry ice is [1] solid carbon dioxide. It is commonly used as a versatile cooling agent.
Dry ice sublimates, changing directly to a gas at atmospheric pressure. Its sublimation and deposition point is -78.5 °C (-109.3 °F). Its enthalpy of sublimation (ΔHsub) at -78.5 °C (-109.3 °F) is 571 kJ/kg (245.5 BTU/lb). The low temperature and direct sublimation to a gas makes dry ice a very effective coolant, since it is colder than ice and leaves no moisture as it changes state.[2] (Although it can carbonate food that is near).
# History
In 1835 the French chemist Charles Thilorier published the first account of dry ice.[3][4]
Upon opening the lid of a large cylinder containing liquid carbon dioxide he noted much of the carbon dioxide rapidly evaporated leaving solid dry ice in the container. Throughout the next 60 years, dry ice was observed and tested by scientists.
# Manufacture
Dry ice is readily manufactured:[5][6]
- Gases containing a high concentration of carbon dioxide are produced. Such gases can be a byproduct of some other process, such as producing ammonia and nitrogen from natural gas, or large-scale fermentation.[6]
- Carbon dioxide-rich gas is pressurized and refrigerated until it changes into its liquid form.
- The pressure is reduced. When this occurs some liquid carbon dioxide vaporizes, and this causes a rapid lowering of temperature of the remaining liquid carbon dioxide. The extreme cold makes the liquid solidify into a snow-like consistency.
- The snow-like solid carbon dioxide is compressed into either small pellets or larger blocks of dry ice.
Dry ice is typically produced in two standard forms: blocks and cylindrical pellets. A standard block weighing approximately 30 kg is most common. These are commonly used in shipping, because they sublimate slowly due to a relatively small surface area. Pellets are around 1 cm in diameter and can be bagged easily. This form is suited to small scale use, for example at grocery stores and laboratories. Dry ice is also inexpensive; it costs less than US$2 per kilogram.[7]
# Applications
Dry ice is commonly used to package items that need to remain cold or frozen, such as ice cream, without the use of mechanical cooling. In medicine it is used to freeze warts to make removal easier.[8] In the construction industry it is used to loosen floor tiles by shrinking and cracking them, as well as to freeze water in valveless pipes to allow repair. In laboratories, a slurry of dry ice in an organic solvent is a useful freezing mixture for cold chemical reactions.
Dry ice can also be used for making ice cream.[9]
Dry ice can be used in theatre productions in order to create the effect of dense fog.
Dry ice can be used to carbonate water and other liquids such as soft drink and beer.[citation needed] It can be used as bait to trap mosquitoes and other insects[10]
When dry ice is placed in water sublimation is accelerated, and low-sinking dense clouds of fog (smoke like) are created. This is used in fog machines, at theaters, discoteques, Halloween, and nightclubs for dramatic effects. When used in theatre productions it creates the effect of dense fog.
Dry Ice is also used in cloud seeding: the process of altering cloud precipitation.
## Dry ice blasting
One of the largest alternative uses of dry ice is blast cleaning. Dry ice pellets are shot out of a nozzle with compressed air. This can remove residues from industrial equipment. Examples of materials being removed include ink, glue, oil, paint, mold and rubber. Dry ice blasting can replace sandblasting, steam blasting, water blasting or solvent blasting. The primary environmental residue of dry ice blasting is the sublimed CO2, thus making it a useful technique where residues from other blasting techniques are undesirable.[11] | https://www.wikidoc.org/index.php/Dry_ice | |
05b5433098e8a01aca32fa03ca9a61d75232e2f3 | wikidoc | EIF2AK1 | EIF2AK1
Eukaryotic translation initiation factor 2-alpha kinase 1 is an enzyme that in humans is encoded by the EIF2AK1 gene.
# Function
EIF2AK1 inhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. EIF2AK1 exerts its function through the phosphorylation of EIF2S1 at 'Ser-48' and 'Ser-51', thus preventing its recycling. Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell. Owing to this unique heme-sensing capacity, it plays a crucial role in shutting off protein synthesis during acute heme-deficient conditions. In red blood cells (RBCs), it controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of the heme and globin moieties of hemoglobin. Thus plays an essential protective role for RBC survival in anemias of iron deficiency. Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes. EIF2AK1 also act to moderate ER stress during acute heme-deficient conditions.
# Enzymology
EIF2AK1 is a kinase, thus it catalyses the following reaction:
ATP + a protein = ADP + a phosphoprotein
EIF2AK1 is induced by acute heme depletion, that not only increases EIF2AK1 protein levels, but also stimulates kinase activity by autophosphorylation. Inhibited by the heme-degradation products biliverdin and bilirubin. Induced by oxidative stress generated by arsenite treatment. Binding of nitric oxide (NO) to the heme iron in the N-terminal heme-binding domain activates the kinase activity, while binding of carbon monoxide (CO) suppresses kinase activity.
cite:
The HRI gene is localized to 7p22 where its 3' end slightly overlaps the 3' end of the gene JTV1. The two genes are transcribed from opposite strands. Studies in rat and rabbit suggest that the HRI gene product phosphorylates the alpha subunit of eukaryotic initiation factor 2. Its kinase activity is induced by low levels of heme and inhibited by the presence of heme. | EIF2AK1
Eukaryotic translation initiation factor 2-alpha kinase 1 is an enzyme that in humans is encoded by the EIF2AK1 gene.[1][2][3]
# Function
EIF2AK1 inhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. EIF2AK1 exerts its function through the phosphorylation of EIF2S1 at 'Ser-48' and 'Ser-51', thus preventing its recycling. Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell. Owing to this unique heme-sensing capacity, it plays a crucial role in shutting off protein synthesis during acute heme-deficient conditions. In red blood cells (RBCs), it controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of the heme and globin moieties of hemoglobin. Thus plays an essential protective role for RBC survival in anemias of iron deficiency. Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes. EIF2AK1 also act to moderate ER stress during acute heme-deficient conditions.
# Enzymology
EIF2AK1 is a kinase, thus it catalyses the following reaction:
ATP + a protein = ADP + a phosphoprotein
EIF2AK1 is induced by acute heme depletion, that not only increases EIF2AK1 protein levels, but also stimulates kinase activity by autophosphorylation. Inhibited by the heme-degradation products biliverdin and bilirubin. Induced by oxidative stress generated by arsenite treatment. Binding of nitric oxide (NO) to the heme iron in the N-terminal heme-binding domain activates the kinase activity, while binding of carbon monoxide (CO) suppresses kinase activity.
cite:https://www.uniprot.org/uniprot/Q9BQI3
The HRI gene is localized to 7p22 where its 3' end slightly overlaps the 3' end of the gene JTV1. The two genes are transcribed from opposite strands. Studies in rat and rabbit suggest that the HRI gene product phosphorylates the alpha subunit of eukaryotic initiation factor 2. Its kinase activity is induced by low levels of heme and inhibited by the presence of heme.[3] | https://www.wikidoc.org/index.php/EIF2AK1 | |
316e186691573f2ab068a27a5ce21daee2a02ea3 | wikidoc | Eardrum | Eardrum
The tympanic membrane, colloquially known as the eardrum, is a thin membrane that separates the external ear from the middle ear. Its function is to transmit sound vibrations from the air, conducted through the external acoustic meatus to the ossicles inside the middle ear. The malleus bone bridges the gap between the eardrum and the other ossicles.
Arterial supply - outer surface is supplied by the deep auricular branch of the maxillary artery,inner surface is supplied by the anterior tympanic branch of the maxillary artery & by the posterior tympanic branch of the stylomastoid branch of the posterior auricular artery.
Venous drainage - outer surface drains into the external jugular vein.inner surface drains into the transverse sinus & into the venous plexus around the auditory tube.
Lymphatic drainage – pass to the preauricular & retropharyngeal nodes.
Nerve supply – Outer surface – anteroinferior part is supplied by the auriculotemporal nerve & the posterosuperior part by the auricular branch of the vagus nerve. Inner surface is supplied by the tympanic branch of the glossopharyngeal nerve through the tympanic plexus.
Rupture or perforation of the eardrum can lead to conductive hearing loss.
# Development
The eardrum forms from the joining of the expanding first pharyngeal pouch and groove. Around day 30 of gestation, the endoderm-lined first expands to form the tympanic cavity, which subsequently envelops the inner ear ossicles. Simultaneously, the first pharyngeal groove, which is lined with ectoderm, expands to form the developing external auditory meatus. Separated by a thin layer of splanchnic mesoderm, the tympanic cavity and external auditory meatus join to form the tympanic membrane. As a result, the tympanic membrane is one of very few adult structures that is derived from all three germ layers. The skin that covers the outer surface of the tympanic membrane is derived from ectoderm, the fibrous tissue that forms the actual membrane is derived from mesoderm, and the mucus membrane that lines the inner surface of the membrane is derived from endoderm.
# Clinical Aspects
When examining the tympanic membrane with an otoscope, a bright cone of light is seen in the anterior-inferior part of the membrane. This light is known as the "cone of light" or "light reflex". The tympanic membrane is separated into four quadrants, with the center of the four quadrants being the umbo. Nerves, specifically the chorda tympani nerve, and arteries pass through the layers of the superior portion of the membrane. Thus, when the tympanic membrane needs to be incised for medical procedures, ENT surgeons will always cut through the inferior and posterior part of the membrane to avoid the vasculature, nerves, and bones associated with the membrane.
# Additional images
- External and middle ear, opened from the front. Right side.
- Horizontal section through left ear; upper half of section.
- The right membrana tympani with the hammer and the chorda tympani, viewed from within, from behind, and from above.
- Auditory tube, laid open by a cut in its long axis.
- Chain of ossicles and their ligaments, seen from the front in a vertical, transverse section of the tympanum. | Eardrum
Template:Infobox Anatomy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
The tympanic membrane, colloquially known as the eardrum, is a thin membrane that separates the external ear from the middle ear. Its function is to transmit sound vibrations from the air, conducted through the external acoustic meatus to the ossicles inside the middle ear. The malleus bone bridges the gap between the eardrum and the other ossicles.
Arterial supply - outer surface is supplied by the deep auricular branch of the maxillary artery,inner surface is supplied by the anterior tympanic branch of the maxillary artery & by the posterior tympanic branch of the stylomastoid branch of the posterior auricular artery.
Venous drainage - outer surface drains into the external jugular vein.inner surface drains into the transverse sinus & into the venous plexus around the auditory tube.
Lymphatic drainage – pass to the preauricular & retropharyngeal nodes.
Nerve supply – Outer surface – anteroinferior part is supplied by the auriculotemporal nerve & the posterosuperior part by the auricular branch of the vagus nerve. Inner surface is supplied by the tympanic branch of the glossopharyngeal nerve through the tympanic plexus.
Rupture or perforation of the eardrum can lead to conductive hearing loss.
# Development
The eardrum forms from the joining of the expanding first pharyngeal pouch and groove. Around day 30 of gestation, the endoderm-lined first expands to form the tympanic cavity, which subsequently envelops the inner ear ossicles. Simultaneously, the first pharyngeal groove, which is lined with ectoderm, expands to form the developing external auditory meatus. Separated by a thin layer of splanchnic mesoderm, the tympanic cavity and external auditory meatus join to form the tympanic membrane. As a result, the tympanic membrane is one of very few adult structures that is derived from all three germ layers. The skin that covers the outer surface of the tympanic membrane is derived from ectoderm, the fibrous tissue that forms the actual membrane is derived from mesoderm, and the mucus membrane that lines the inner surface of the membrane is derived from endoderm.
# Clinical Aspects
When examining the tympanic membrane with an otoscope, a bright cone of light is seen in the anterior-inferior part of the membrane. This light is known as the "cone of light" or "light reflex". The tympanic membrane is separated into four quadrants, with the center of the four quadrants being the umbo. Nerves, specifically the chorda tympani nerve, and arteries pass through the layers of the superior portion of the membrane. Thus, when the tympanic membrane needs to be incised for medical procedures, ENT surgeons will always cut through the inferior and posterior part of the membrane to avoid the vasculature, nerves, and bones associated with the membrane.
# Additional images
- External and middle ear, opened from the front. Right side.
- Horizontal section through left ear; upper half of section.
- The right membrana tympani with the hammer and the chorda tympani, viewed from within, from behind, and from above.
- Auditory tube, laid open by a cut in its long axis.
- Chain of ossicles and their ligaments, seen from the front in a vertical, transverse section of the tympanum.
# External links
- Diagram at Georgia State University
- drtbalu's otolaryngology online
Template:Auditory system
de:Trommelfell
et:Trummikile
id:Gendang telinga
it:Timpano (anatomia)
he:עור התוף
la:Membrana tympani
lt:Būgnelis
nl:Trommelvlies
no:Trommehinne
nn:Trommehinne
sk:Bubienok (cicavce)
sr:Бубна опна
fi:Tärykalvo
uk:Барабанна перетинка
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Ear_drum | |
bc788c074db4ed0ccddbb98bf4d6fc34264b13f8 | wikidoc | Earlobe | Earlobe
# Overview
On the ear of humans and many other animals, the earlobe (lobulus auriculæ, sometimes simply lobe or lobule) is the soft lower part of the external ear, similar in composition to the labia, or pinna. It is the lowermost portion of the human pinna, projecting below the antitragus. The earlobe is composed of tough areolar and adipose (fatty) connective tissues, lacking the firmness and elasticity of the rest of the pinna, since the earlobe contains no cartilage. Earlobes have a large blood supply and may help to warm the ears, but generally earlobes are not considered to have any biological function.
# Size and shape
Earlobes average about 2 cm long, and enlongate slightly with age. Human earlobes may be free (hanging free from the head) or attached (joined to the head). Whether the earlobe is free or attached is a classic example of a simple genetic dominance relationship; freely hanging earlobes are the dominant allele and attached earlobes are recessive. Therefore, a person whose genes contain one allele for free earlobes and one for attached lobes will display the freely hanging lobe trait. Genetically dominant, free earlobes are twice as common in the human population as attached lobes.
Earlobes are normally smooth, but occasionally exhibit creases. Creased earlobes are associated with genetic disorders, including Beckwith-Wiedemann syndrome. Earlobe creases are also associated with an increased risk of heart attack and coronary heart disease; however, since earlobes become more creased with age, and older people are more likely to experience heart disease than younger people, age may account for the findings linking heart attack to earlobe creases.
The earlobe contains many nerve endings and consequently is an erogenous zone.
# Earlobe piercing
Around the world and throughout human history, the earlobe is the most common location for a body piercing. Tearing of the earlobe from the weight of very heavy earrings, or traumatic pull of an earring, is fairly common. The repair of such a tear is usually not difficult. Some cultures practice earlobe stretching, using piercing ornaments to stretch and enlarge the earlobes. Piercing the earlobe poses a much lower risk of infection than piercing other parts of the ear. Initial healing time for an earlobe piercing is typically 6-8 weeks. After that time, earrings can be changed, but if the hole is left unfilled for an extended period of time, there is some danger of the piercing closing. After healing, earlobe piercings will shrink to smaller gauges in the prolonged absence of earrings, but may never completely disappear. | Earlobe
Template:Infobox Anatomy
# Overview
On the ear of humans and many other animals, the earlobe (lobulus auriculæ, sometimes simply lobe or lobule) is the soft lower part of the external ear, similar in composition to the labia, or pinna. It is the lowermost portion of the human pinna, projecting below the antitragus. The earlobe is composed of tough areolar and adipose (fatty) connective tissues, lacking the firmness and elasticity of the rest of the pinna, since the earlobe contains no cartilage. Earlobes have a large blood supply and may help to warm the ears, but generally earlobes are not considered to have any biological function.[1]
# Size and shape
Earlobes average about 2 cm long, and enlongate slightly with age.[2] Human earlobes may be free (hanging free from the head) or attached (joined to the head). Whether the earlobe is free or attached is a classic example of a simple genetic dominance relationship; freely hanging earlobes are the dominant allele and attached earlobes are recessive. Therefore, a person whose genes contain one allele for free earlobes and one for attached lobes will display the freely hanging lobe trait. Genetically dominant, free earlobes are twice as common in the human population as attached lobes.
Earlobes are normally smooth, but occasionally exhibit creases. Creased earlobes are associated with genetic disorders, including Beckwith-Wiedemann syndrome. Earlobe creases are also associated with an increased risk of heart attack and coronary heart disease; however, since earlobes become more creased with age, and older people are more likely to experience heart disease than younger people, age may account for the findings linking heart attack to earlobe creases.[3]
The earlobe contains many nerve endings and consequently is an erogenous zone.
# Earlobe piercing
Around the world and throughout human history, the earlobe is the most common location for a body piercing. Tearing of the earlobe from the weight of very heavy earrings, or traumatic pull of an earring, is fairly common. The repair of such a tear is usually not difficult. Some cultures practice earlobe stretching, using piercing ornaments to stretch and enlarge the earlobes. Piercing the earlobe poses a much lower risk of infection than piercing other parts of the ear. Initial healing time for an earlobe piercing is typically 6-8 weeks. After that time, earrings can be changed, but if the hole is left unfilled for an extended period of time, there is some danger of the piercing closing. After healing, earlobe piercings will shrink to smaller gauges in the prolonged absence of earrings, but may never completely disappear. | https://www.wikidoc.org/index.php/Ear_lobe | |
afbc27f9c3dc7a27ba79159984931ce9d8879973 | wikidoc | Echidna | Echidna
Echidnas (Template:PronEng), also known as spiny anteaters, are four extant mammal species belonging to the Tachyglossidae family of the monotremes. Together with the Platypus, they are the only surviving members of that order. Although their diet consists largely of ants and termites, they are not actually related to the anteater species. They live in New Guinea and Australia. The echidnas are named after a monster in ancient Greek mythology.
# Description
Echidnas are small mammals that are covered with coarse hair and spines. Superficially they resemble the anteaters of South America, and other spiny mammals like hedgehogs and porcupines. They have snouts which have the functions of both the mouth and nose. Their snouts are elongated and slender. They have very short, strong limbs with large claws and are powerful diggers. Echidnas have a tiny mouth and a toothless jaw. They feed by tearing open soft logs, anthills and the like, and use their long, sticky tongue which protrudes from their snout to collect their prey. The Short-beaked Echidna's diet consists largely of ants and termites, while the Zaglossus species typically eat worms and insect larvae.
The long-beaked echidnas have tiny spines on their tongues that helps capture its meals.
Echidnas and the Platypus are the only egg-laying mammals, known as monotremes. The female lays a single soft-shelled, leathery egg twenty-two days after mating and deposits it directly into her pouch. Hatching takes ten days; the young echidna, called a puggle, then sucks milk from the pores of the two milk patches (monotremes have no nipples) and remains in the pouch for forty-five to fifty-five days, at which time it starts to develop spines. The mother digs a nursery burrow and deposits the puggle, returning every five days to suckle it until it is weaned at seven months.
Male echidnas have a four-headed penis, but only two of the heads are used during mating. The other two heads "shut down" and do not grow in size. The heads used are swapped each time the mammal has sex.
# Taxonomy
Echidnas are classified into three genera. The Zaglossus genus includes three extant species and two species known only from fossils, while only one species from the genus Tachyglossus is known. The third genus, Megalibgwilia, is only known from fossils.
## Zaglossus
The three living Zaglossus species are endemic to New Guinea. They are rare and are hunted for food. They forage in leaf litter on the forest floor, eating earthworms and insects. The species are:
- the Western Long-beaked Echidna (Zaglossus bruijni) of the highland forests
- Sir David's Long-beaked Echidna (Zaglossus attenboroughi), recently discovered, prefers a still higher habitat
- the Eastern Long-beaked Echidna (Zaglossus bartoni), of which four distinct subspecies have been identified
The two fossil species are:
- Zaglossus robustus
- Zaglossus hacketti
## Tachyglossus
The Short-beaked Echidna (Tachyglossus aculeatus) is found in southeast New Guinea and also occurs in almost all Australian environments, from the snow-clad Australian Alps to the deep deserts of the Outback, essentially anywhere that ants and termites are available. Its size is smaller than the Zaglossus species, and it has longer hair.
## Megalibgwilia
The genus Megalibgwilia is only known from fossils:
- Megalibgwilia ramsayi from Late Pleistocene sites in Australia
- Megalibgwilia robusta from Miocene sites in Australia
# Media | Echidna
Echidnas (Template:PronEng), also known as spiny anteaters, [2] are four extant mammal species belonging to the Tachyglossidae family of the monotremes. Together with the Platypus, they are the only surviving members of that order. Although their diet consists largely of ants and termites, they are not actually related to the anteater species. They live in New Guinea and Australia. The echidnas are named after a monster in ancient Greek mythology.
# Description
Echidnas are small mammals that are covered with coarse hair and spines. Superficially they resemble the anteaters of South America, and other spiny mammals like hedgehogs and porcupines. They have snouts which have the functions of both the mouth and nose. Their snouts are elongated and slender. They have very short, strong limbs with large claws and are powerful diggers. Echidnas have a tiny mouth and a toothless jaw. They feed by tearing open soft logs, anthills and the like, and use their long, sticky tongue which protrudes from their snout to collect their prey. The Short-beaked Echidna's diet consists largely of ants and termites, while the Zaglossus species typically eat worms and insect larvae.
The long-beaked echidnas have tiny spines on their tongues that helps capture its meals.
Echidnas and the Platypus are the only egg-laying mammals, known as monotremes. The female lays a single soft-shelled, leathery egg twenty-two days after mating and deposits it directly into her pouch. Hatching takes ten days; the young echidna, called a puggle, then sucks milk from the pores of the two milk patches (monotremes have no nipples) and remains in the pouch for forty-five to fifty-five days, at which time it starts to develop spines. The mother digs a nursery burrow and deposits the puggle, returning every five days to suckle it until it is weaned at seven months.
Male echidnas have a four-headed penis, but only two of the heads are used during mating. The other two heads "shut down" and do not grow in size. The heads used are swapped each time the mammal has sex.[3]
# Taxonomy
Echidnas are classified into three genera. The Zaglossus genus includes three extant species and two species known only from fossils, while only one species from the genus Tachyglossus is known. The third genus, Megalibgwilia, is only known from fossils.
## Zaglossus
The three living Zaglossus species are endemic to New Guinea. They are rare and are hunted for food. They forage in leaf litter on the forest floor, eating earthworms and insects. The species are:
- the Western Long-beaked Echidna (Zaglossus bruijni) of the highland forests
- Sir David's Long-beaked Echidna (Zaglossus attenboroughi), recently discovered, prefers a still higher habitat
- the Eastern Long-beaked Echidna (Zaglossus bartoni), of which four distinct subspecies have been identified
The two fossil species are:
- Zaglossus robustus
- Zaglossus hacketti
## Tachyglossus
The Short-beaked Echidna (Tachyglossus aculeatus) is found in southeast New Guinea and also occurs in almost all Australian environments, from the snow-clad Australian Alps to the deep deserts of the Outback, essentially anywhere that ants and termites are available. Its size is smaller than the Zaglossus species, and it has longer hair.
## Megalibgwilia
The genus Megalibgwilia is only known from fossils:
- Megalibgwilia ramsayi from Late Pleistocene sites in Australia
- Megalibgwilia robusta from Miocene sites in Australia
# Media | https://www.wikidoc.org/index.php/Echidna | |
44b3153708d82ddcb92cfe45968d287522e74934 | wikidoc | Ecology | Ecology
Ecology (from Greek: οίκος, oikos, "household"; and λόγος, logos, "knowledge") is the scientific study of the distribution and abundance of life and the interactions between organisms and their environment. The environment of an organism includes physical properties, which can be described as the sum of local abiotic factors such as insolation (sunlight), climate, and geology, and biotic factors, which are other organisms that share its habitat.
The word "ecology" is often used more loosely in such terms as social ecology and deep ecology and in common parlance as a synonym for the natural environment or environmentalism. Likewise "ecologic" or "ecological" is often taken in the sense of environmentally friendly.
The term ecology or oekologie was coined by the German biologist Ernst Haeckel in 1866, when he defined it as "the comprehensive science of the relationship of the organism to the environment." Haeckel did not elaborate on the concept, and the first significant textbook on the subject (together with the first university course) was written by the Danish botanist, Eugenius Warming. For this early work, Warming is often identified as the founder of ecology.
# Scope
Ecology is usually considered a branch of biology, the general science that studies living organisms. Organisms can be studied at many different levels, from proteins and nucleic acids (in biochemistry and molecular biology), to cells (in cellular biology), to individuals (in botany, zoology, and other similar disciplines), and finally at the level of populations, communities, and ecosystems, to the biosphere as a whole; these latter strata are the primary subjects of ecological inquiry. Ecology is a multi-disciplinary science. Because of its focus on the higher levels of the organization of life on earth and on the interrelations between organisms and their environment, ecology draws heavily on many other branches of science, especially geology and geography, meteorology, pedology, genetics, chemistry, and physics. Thus, ecology is considered by some to be a holistic science, one that over-arches older disciplines such as biology which in this view become sub-disciplines contributing to ecological knowledge. In support of viewing ecology as a subject in its own right as opposed to a sub-discipline of biology, Robert Ulanowicz stated that "The emerging picture of ecosystem behavior does not resemble the worldview imparted by an extrapolation of conceptual trends established in other sciences."
Agriculture, fisheries, forestry, medicine and urban development are among human activities that would fall within Krebs' (1972: 4) explanation of his definition of ecology: where organisms are found, how many occur there, and why.
Ecological knowledge such as the quantification of biodiversity and population dynamics have provided a scientific basis for expressing the aims of environmentalism and evaluating its goals and policies. Additionally, a holistic view of nature is stressed in both ecology and environmentalism.
Consider the ways an ecologist might approach studying the life of honeybees:
- The behavioral relationship between individuals of a species is behavioral ecology — for example, the study of the queen bee, and how she relates to the worker bees and the drones.
- The organized activity of a species is community ecology; for example, the activity of bees assures the pollination of flowering plants. Bee hives additionally produce honey which is consumed by still other species, such as bears.
- The relationship between the environment and a species is environmental ecology — for example, the consequences of environmental change on bee activity. Bees may die out due to environmental changes (see pollinator decline). The environment simultaneously affects and is a consequence of this activity and is thus intertwined with the survival of the species.
## Disciplines of ecology
Ecology is a broad discipline comprising many sub-disciplines. A common, broad classification, moving from lowest to highest complexity, where complexity is defined as the number of entities and processes in the system under study, is:
- Ecophysiology examines how the physiological functions of organisms influence the way they interact with the environment, both biotic and abiotic
- Behavioral ecology examines the roles of behavior in enabling an animal to adapt to its environment
- Population ecology studies the dynamics of populations of a single species.
- Community ecology (or synecology) focuses on the interactions between species within an ecological community.
- Ecosystem ecology studies the flows of energy and matter through the biotic and abiotic components of ecosystems.
- Systems ecology is an interdisciplinary field focusing on the study, development, and organization of ecological systems from a holistic perspective.
- Landscape ecology examines processes and relationship across multiple ecosystems or very large geographic areas.
- Evolutionary ecology studies ecology in a way that explicitly considers the evolutionary histories of species and their interactions
- Political ecology connects politics and economy to problems of environmental control and ecological change
Ecology can also be sub-divided according to the species of interest into fields such as animal ecology, plant ecology, insect ecology, and so on. Another frequent method of subdivision is by biome studied, e.g., Arctic ecology (or polar ecology), tropical ecology, desert ecology, etc. The primary technique used for investigation is often used to subdivide the discipline into groups such as chemical ecology, genetic ecology, field ecology, statistical ecology, theoretical ecology, and so forth. These fields are not mutually exclusive.
# History of ecology
# Fundamental principles of ecology
## Levels of ecological organization
Ecology can be studied at a wide range of levels, from a large to small scale. These levels of ecological organization, as well as an example of a question ecologists would ask at each level, include:
- Biosphere " What role does concentration of atmospheric Carbon Dioxide play in the regulation of global temperature?"
- Region "How has geological history influenced regional diversity within certain groups of organisms?"
- Landscape "How do vegetated corridors affect the rate of movement by mammals among isolated fragments?"
- Ecosystem "How does fire affect nutrient availability in grassland ecosystems?"
- Community "How does disturbance influence the number of mammal species in African grasslands?"
- Interactions "What evolutionary benefit do zebras gain by allowing birds to remove parasites?"
- Population "What factors control zebra populations?"
- Individual "How do zebras regulate internal water balance?"
These levels range from broadest to most specific
- These levels range from broadest to most specific
## Biosphere
For modern ecologists, ecology can be studied at several levels: population level (individuals of the same species in the same or similar environment), biocoenosis level (or community of species), ecosystem level, and biosphere level.
The outer layer of the planet Earth can be divided into several compartments: the hydrosphere (or sphere of water), the lithosphere (or sphere of soils and rocks), and the atmosphere (or sphere of the air). The biosphere (or sphere of life), sometimes described as "the fourth envelope", is all living matter on the planet or that portion of the planet occupied by life. It reaches well into the other three spheres, although there are no permanent inhabitants of the atmosphere. Relative to the volume of the Earth, the biosphere is only the very thin surface layer which extends from 11,000 meters below sea level to 15,000 meters above.
It is thought that life first developed in the hydrosphere, at shallow depths, in the photic zone. (Recently, though, a competing theory has emerged, that life originated around hydrothermal vents in the deeper ocean. See Origin of life.) Multicellular organisms then appeared and colonized benthic zones. Photosynthetic organisms gradually produced the chemically unstable oxygen-rich atmosphere that characterizes our planet. Terrestrial life developed later, after the ozone layer protecting living beings from UV rays formed. Diversification of terrestrial species is thought to be increased by the continents drifting apart, or alternately, colliding. Biodiversity is expressed at the ecological level (ecosystem), population level (intraspecific diversity), species level (specific diversity), and genetic level. Recently technology has allowed the discovery of the deep ocean vent communities. This remarkable ecological system is not dependent on sunlight but bacteria, utilising the chemistry of the hot volcanic vents, are at the base of its food chain.
The biosphere contains great quantities of elements such as carbon, nitrogen, hydrogen and oxygen. Other elements, such as phosphorus, calcium, and potassium, are also essential to life, yet are present in smaller amounts. At the ecosystem and biosphere levels, there is a continual recycling of all these elements, which alternate between the mineral and organic states.
While there is a slight input of geothermal energy, the bulk of the functioning of the ecosystem is based on the input of solar energy. Plants and photosynthetic microorganisms convert light into chemical energy by the process of photosynthesis, which creates glucose (a simple sugar) and releases free oxygen. Glucose thus becomes the secondary energy source which drives the ecosystem. Some of this glucose is used directly by other organisms for energy. Other sugar molecules can be converted to other molecules such as amino acids. Plants use some of this sugar, concentrated in nectar to entice pollinators to aid them in reproduction.
Cellular respiration is the process by which organisms (like mammals) break the glucose back down into its constituents, water and carbon dioxide, thus regaining the stored energy the sun originally gave to the plants. The proportion of photosynthetic activity of plants and other photosynthesizers to the respiration of other organisms determines the specific composition of the Earth's atmosphere, particularly its oxygen level. Global air currents mix the atmosphere and maintain nearly the same balance of elements in areas of intense biological activity and areas of slight biological activity.
Water is also exchanged between the hydrosphere, lithosphere, atmosphere and biosphere in regular cycles. The oceans are large tanks, which store water, ensure thermal and climatic stability, as well as the transport of chemical elements thanks to large oceanic currents.
For a better understanding of how the biosphere works, and various dysfunctions related to human activity, American scientists simulated the biosphere in a small-scale model, called Biosphere II.
## The ecosystem concept
The first principle of ecology is that each living organism has an ongoing and continual relationship with every other element that makes up its environment. An ecosystem can be defined as any situation where there is interaction between organisms and their environment.
The ecosystem is of two entities, the entirety of life, the biocoenosis, and the medium that life exists in, the biotope. Within the ecosystem, species are connected by food chains or food webs. Energy from the sun, captured by primary producers via photosynthesis, flows upward through the chain to primary consumers (herbivores), and then to secondary and tertiary consumers (carnivores and omnivores), before ultimately being lost to the system as waste heat. In the process, matter is incorporated into living organisms, which return their nutrients to the system via decomposition, forming biogeochemical cycles such as the carbon and nitrogen cycles.
The concept of an ecosystem can apply to units of variable size, such as a pond, a field, or a piece of dead wood. An ecosystem within another ecosystem is called a micro ecosystem. For example, an ecosystem can be a stone and all the life under it. A meso ecosystem could be a forest, and a macro ecosystem a whole eco region, with its drainage basin.
The main questions when studying an ecosystem are:
- Whether the colonization of a barren area could be carried out
- Investigation the ecosystem's dynamics and changes
- The methods of which an ecosystem interacts at local, regional and global scale
- Whether the current state is stable
- Investigating the value of an ecosystem and the ways and means that interaction of ecological systems provides benefits to humans, especially in the provision of healthy water.
Ecosystems are often classified by reference to the biotopes concerned. The following ecosystems may be defined:
- As continental ecosystems, such as forest ecosystems, meadow ecosystems such as steppes or savannas, or agro-ecosystems
- As ecosystems of inland waters, such as lentic ecosystems such as lakes or ponds; or lotic ecosystems such as rivers
- As oceanic ecosystems.
Another classification can be done by reference to its communities, such as in the case of an human ecosystem.
## Dynamics and stability
Ecological factors which affect dynamic change in a population or species in a given ecology or environment are usually divided into two groups: abiotic and biotic.
Abiotic factors are geological, geographical, hydrological and climatological parameters. A biotope is an environmentally uniform region characterized by a particular set of abiotic ecological factors. Specific abiotic factors include:
- Water, which is at the same time an essential element to life and a milieu
- Air, which provides oxygen, nitrogen, and carbon dioxide to living species and allows the dissemination of pollen and spores
- Soil, at the same time source of nutriment and physical support
Soil pH, salinity, nitrogen and phosphorus content, ability to retain water, and density are all influential
- Soil pH, salinity, nitrogen and phosphorus content, ability to retain water, and density are all influential
- Temperature, which should not exceed certain extremes, even if tolerance to heat is significant for some species
- Light, which provides energy to the ecosystem through photosynthesis
- Natural disasters can also be considered abiotic
Biocenose, or community, is a group of populations of plants, animals, micro-organisms. Each population is the result of procreations between individuals of same species and cohabitation in a given place and for a given time. When a population consists of an insufficient number of individuals, that population is threatened with extinction; the extinction of a species can approach when all biocenoses composed of individuals of the species are in decline. In small populations, consanguinity (inbreeding) can result in reduced genetic diversity that can further weaken the biocenose.
Biotic ecological factors also influence biocenose viability; these factors are considered as either intraspecific and interspecific relations.
The existing interactions between the various living beings go along with a permanent mixing of mineral and organic substances, absorbed by organisms for their growth, their maintenance and their reproduction, to be finally rejected as waste. These permanent recyclings of the elements (in particular carbon, oxygen and nitrogen) as well as the water are called biogeochemical cycles. They guarantee a durable stability of the biosphere (at least when unchecked human influence and extreme weather or geological phenomena are left aside). This self-regulation, supported by negative feedback controls, ensures the perenniality of the ecosystems. It is shown by the very stable concentrations of most elements of each compartment. This is referred to as homeostasis. The ecosystem also tends to evolve to a state of ideal balance, reached after a succession of events, the climax (for example a pond can become a peat bog).
## Spatial relationships and subdivisions of land
Ecosystems are not isolated from each other, but are interrelated. For example, water may circulate between ecosystems by the means of a river or ocean current. Water itself, as a liquid medium, even defines ecosystems. Some species, such as salmon or freshwater eels move between marine systems and fresh-water systems. These relationships between the ecosystems lead to the concept of a biome.
A biome is a homogeneous ecological formation that exists over a large region as tundra or steppes. The biosphere comprises all of the Earth's biomes -- the entirety of places where life is possible -- from the highest mountains to the depths of the oceans.
Biomes correspond rather well to subdivisions distributed along the latitudes, from the equator towards the poles, with differences based on to the physical environment (for example, oceans or mountain ranges) and to the climate. Their variation is generally related to the distribution of species according to their ability to tolerate temperature and/or dryness. For example, one may find photosynthetic algae only in the photic part of the ocean (where light penetrates), while conifers are mostly found in mountains.
Though this is a simplification of more complicated scheme, latitude and altitude approximate a good representation of the distribution of biodiversity within the biosphere. Very generally, the richness of biodiversity (as well for animal than plant species) is decreasing most rapidly near the equator and less rapidly as one approaches the poles.
The biosphere may also be divided into ecozones, which are very well defined today and primarily follow the continental borders. The ecozones are themselves divided into ecoregions, though there is not agreement on their limits.
## Ecosystem productivity
In an ecosystem, the connections between species are generally related to food and their role in the food chain. There are three categories of organisms:
- Producers -- usually plants which are capable of photosynthesis but could be other organisms such as bacteria around ocean vents that are capable of chemosynthesis.
- Consumers -- animals, which can be primary consumers (herbivorous), or secondary or tertiary consumers (carnivorous and omnivores).
- Decomposers -- bacteria, mushrooms which degrade organic matter of all categories, and restore minerals to the environment. And decomposers can also decompose decaying animals
These relations form sequences, in which each individual consumes the preceding one and is consumed by the one following, in what are called food chains or food network. In a food network, there will be fewer organisms at each level as one follows the links of the network up the chain.
These concepts lead to the idea of biomass (the total living matter in a given place), of primary productivity (the increase in the mass of plants during a given time) and of secondary productivity (the living matter produced by consumers and the decomposers in a given time).
These two last ideas are key, since they make it possible to evaluate the load capacity -- the number of organisms which can be supported by a given ecosystem. In any food network, the energy contained in the level of the producers is not completely transferred to the consumers. And the higher one goes up the chain, the more energy and resources is lost and consumed. Thus, from an energy—and environmental—point of view, it is more efficient for humans to be primary consumers (to subsist from vegetables, grains, legumes, fruit, etc.) than as secondary consumers (from eating herbivores, omnivores, or their products, such as milk, chickens, cattle, sheep, etc.) and still more so than as a tertiary consumer (from consuming carnivores, omnivores, or their products, such as fur, pigs, snakes, alligators, etc.). An ecosystem(s) is unstable when the load capacity is overrun and is especially unstable when a population doesn't have an ecological niche and overconsumers.
The productivity of ecosystems is sometimes estimated by comparing three types of land-based ecosystems and the total of aquatic ecosystems:
- The forests (1/3 of the Earth's land area) contain dense biomasses and are very productive. The total production of the world's forests corresponds to half of the primary production.
- Savannas, meadows, and marshes (1/3 of the Earth's land area) contain less dense biomasses, but are productive. These ecosystems represent the major part of what humans depend on for food.
- Extreme ecosystems in the areas with more extreme climates -- deserts and semi-deserts, tundra, alpine meadows, and steppes -- (1/3 of the Earth's land area) have very sparse biomasses and low productivity
- Finally, the marine and fresh water ecosystems (3/4 of Earth's surface) contain very sparse biomasses (apart from the coastal zones).
Humanity's actions over the last few centuries have seriously reduced the amount of the Earth covered by forests (deforestation), and have increased agro-ecosystems (agriculture). In recent decades, an increase in the areas occupied by extreme ecosystems has occurred (desertification).
## Ecological crisis
Generally, an ecological crisis occurs with the loss of adaptive capacity when the resilience of an environment or of a species or a population evolves in a way unfavourable to coping with perturbations that interfere with that ecosystem, landscape or species survival. It may be that the environment quality degrades compared to the species needs, after a change in an abiotic ecological factor (for example, an increase of temperature, less significant rainfalls). It may be that the environment becomes unfavourable for the survival of a species (or a population) due to an increased pressure of predation (for example overfishing). Lastly, it may be that the situation becomes unfavourable to the quality of life of the species (or the population) due to a rise in the number of individuals (overpopulation).
Ecological crises vary in length and severity, occurring within a few months or taking as long as a few million years. They can also be of natural or anthropic origin. They may relate to one unique species or to many species, as in an Extinction event. Lastly, an ecological crisis may be local (as an oil spill) or global (a rise in the sea level due to global warming).
According to its degree of endemism, a local crisis will have more or less significant consequences, from the death of many individuals to the total extinction of a species. Whatever its origin, disappearance of one or several species often will involve a rupture in the food chain, further impacting the survival of other species.
In the case of a global crisis, the consequences can be much more significant; some extinction events showed the disappearance of more than 90% of existing species at that time. However, it should be noted that the disappearance of certain species, such as the dinosaurs, by freeing an ecological niche, allowed the development and the diversification of the mammals. An ecological crisis thus paradoxically favored biodiversity.
Sometimes, an ecological crisis can be a specific and reversible phenomenon at the ecosystem scale. But more generally, the crises impact will last. Indeed, it rather is a connected series of events, that occur till a final point. From this stage, no return to the previous stable state is possible, and a new stable state will be set up gradually (see homeorhesy).
Lastly, if an ecological crisis can cause extinction, it can also more simply reduce the quality of life of the remaining individuals. Thus, even if the diversity of the human population is sometimes considered threatened (see in particular indigenous people), few people envision human disappearance at short span. However, epidemic diseases, famines, impact on health of reduction of air quality, food crises, reduction of living space, accumulation of toxic or non degradable wastes, threats on keystone species (great apes, panda, whales) are also factors influencing the well-being of people.
Due to the increases in technology and a rapidly increasing population, humans have more influence on their own environment than any other ecosystem engineer.
Some common examples of ecological crises are:
- The Exxon Valdez oil spill off the coast of Alaska in 1989
- Permian-Triassic extinction event 250 million of years ago
- Cretaceous–Tertiary extinction event 65 million years ago
- Global warming related to the Greenhouse effect. Warming could involve flooding of the Asian deltas (see also eco refugees), multiplication of extreme weather phenomena and changes in the nature and quantity of the food resources (see Global warming and agriculture). See also international Kyoto Protocol.
- Ozone layer hole issue
- Deforestation and desertification, with disappearance of many species.
- Volcanic eruptions such as Mount St. Helens and the Tunguska and other impact events
- The nuclear meltdown at Chernobyl in 1986 caused the death of many people and animals from cancer, and caused mutations in a large number of animals and people. The area around the plant is now abandoned by humans because of the large amount of radiation generated by the meltdown. Twenty years after the accident, the animals have returned.
# Bibliography
- Warming, E. (1909) Oecology of Plants - an introduction to the study of plant-communities. Clarendon Press, Oxford.
- Haeckel, E. (1866) General Morphology of Organisms; General Outlines of the Science of Organic Forms based on Mechanical Principles through the Theory of Descent as reformed by Charles Darwin. Berlin. | Ecology
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Ecology (from Greek: οίκος, oikos, "household"; and λόγος, logos, "knowledge") is the scientific study of the distribution and abundance of life and the interactions between organisms and their environment. The environment of an organism includes physical properties, which can be described as the sum of local abiotic factors such as insolation (sunlight), climate, and geology, and biotic factors, which are other organisms that share its habitat.
The word "ecology" is often used more loosely in such terms as social ecology and deep ecology and in common parlance as a synonym for the natural environment or environmentalism. Likewise "ecologic" or "ecological" is often taken in the sense of environmentally friendly.
The term ecology or oekologie was coined by the German biologist Ernst Haeckel in 1866, when he defined it as "the comprehensive science of the relationship of the organism to the environment."[1] Haeckel did not elaborate on the concept, and the first significant textbook on the subject (together with the first university course) was written by the Danish botanist, Eugenius Warming. For this early work, Warming is often identified as the founder of ecology.[2]
# Scope
Ecology is usually considered a branch of biology, the general science that studies living organisms. Organisms can be studied at many different levels, from proteins and nucleic acids (in biochemistry and molecular biology), to cells (in cellular biology), to individuals (in botany, zoology, and other similar disciplines), and finally at the level of populations, communities, and ecosystems, to the biosphere as a whole; these latter strata are the primary subjects of ecological inquiry. Ecology is a multi-disciplinary science. Because of its focus on the higher levels of the organization of life on earth and on the interrelations between organisms and their environment, ecology draws heavily on many other branches of science, especially geology and geography, meteorology, pedology, genetics, chemistry, and physics. Thus, ecology is considered by some to be a holistic science, one that over-arches older disciplines such as biology which in this view become sub-disciplines contributing to ecological knowledge. In support of viewing ecology as a subject in its own right as opposed to a sub-discipline of biology, Robert Ulanowicz stated that "The emerging picture of ecosystem behavior does not resemble the worldview imparted by an extrapolation of conceptual trends established in other sciences."[3]
Agriculture, fisheries, forestry, medicine and urban development are among human activities that would fall within Krebs' (1972: 4) explanation of his definition of ecology: where organisms are found, how many occur there, and why.
Ecological knowledge such as the quantification of biodiversity and population dynamics have provided a scientific basis for expressing the aims of environmentalism and evaluating its goals and policies. Additionally, a holistic view of nature is stressed in both ecology and environmentalism.
Consider the ways an ecologist might approach studying the life of honeybees:
- The behavioral relationship between individuals of a species is behavioral ecology — for example, the study of the queen bee, and how she relates to the worker bees and the drones.
- The organized activity of a species is community ecology; for example, the activity of bees assures the pollination of flowering plants. Bee hives additionally produce honey which is consumed by still other species, such as bears.
- The relationship between the environment and a species is environmental ecology — for example, the consequences of environmental change on bee activity. Bees may die out due to environmental changes (see pollinator decline). The environment simultaneously affects and is a consequence of this activity and is thus intertwined with the survival of the species.
## Disciplines of ecology
Ecology is a broad discipline comprising many sub-disciplines. A common, broad classification, moving from lowest to highest complexity, where complexity is defined as the number of entities and processes in the system under study, is:
- Ecophysiology examines how the physiological functions of organisms influence the way they interact with the environment, both biotic and abiotic
- Behavioral ecology examines the roles of behavior in enabling an animal to adapt to its environment
- Population ecology studies the dynamics of populations of a single species.
- Community ecology (or synecology) focuses on the interactions between species within an ecological community.
- Ecosystem ecology studies the flows of energy and matter through the biotic and abiotic components of ecosystems.
- Systems ecology is an interdisciplinary field focusing on the study, development, and organization of ecological systems from a holistic perspective.
- Landscape ecology examines processes and relationship across multiple ecosystems or very large geographic areas.
- Evolutionary ecology studies ecology in a way that explicitly considers the evolutionary histories of species and their interactions
- Political ecology connects politics and economy to problems of environmental control and ecological change
Ecology can also be sub-divided according to the species of interest into fields such as animal ecology, plant ecology, insect ecology, and so on. Another frequent method of subdivision is by biome studied, e.g., Arctic ecology (or polar ecology), tropical ecology, desert ecology, etc. The primary technique used for investigation is often used to subdivide the discipline into groups such as chemical ecology, genetic ecology, field ecology, statistical ecology, theoretical ecology, and so forth. These fields are not mutually exclusive.
# History of ecology
# Fundamental principles of ecology
## Levels of ecological organization
Ecology can be studied at a wide range of levels, from a large to small scale. These levels of ecological organization, as well as an example of a question ecologists would ask at each level, include:
- Biosphere " What role does concentration of atmospheric Carbon Dioxide play in the regulation of global temperature?"
- Region "How has geological history influenced regional diversity within certain groups of organisms?"
- Landscape "How do vegetated corridors affect the rate of movement by mammals among isolated fragments?"
- Ecosystem "How does fire affect nutrient availability in grassland ecosystems?"
- Community "How does disturbance influence the number of mammal species in African grasslands?"
- Interactions "What evolutionary benefit do zebras gain by allowing birds to remove parasites?"
- Population "What factors control zebra populations?"
- Individual "How do zebras regulate internal water balance?"
These levels range from broadest to most specific[4]
- These levels range from broadest to most specific[4]
## Biosphere
For modern ecologists, ecology can be studied at several levels: population level (individuals of the same species in the same or similar environment), biocoenosis level (or community of species), ecosystem level, and biosphere level.
The outer layer of the planet Earth can be divided into several compartments: the hydrosphere (or sphere of water), the lithosphere (or sphere of soils and rocks), and the atmosphere (or sphere of the air). The biosphere (or sphere of life), sometimes described as "the fourth envelope", is all living matter on the planet or that portion of the planet occupied by life. It reaches well into the other three spheres, although there are no permanent inhabitants of the atmosphere. Relative to the volume of the Earth, the biosphere is only the very thin surface layer which extends from 11,000 meters below sea level to 15,000 meters above.
It is thought that life first developed in the hydrosphere, at shallow depths, in the photic zone. (Recently, though, a competing theory has emerged, that life originated around hydrothermal vents in the deeper ocean. See Origin of life.) Multicellular organisms then appeared and colonized benthic zones. Photosynthetic organisms gradually produced the chemically unstable oxygen-rich atmosphere that characterizes our planet. Terrestrial life developed later, after the ozone layer protecting living beings from UV rays formed. Diversification of terrestrial species is thought to be increased by the continents drifting apart, or alternately, colliding. Biodiversity is expressed at the ecological level (ecosystem), population level (intraspecific diversity), species level (specific diversity), and genetic level. Recently technology has allowed the discovery of the deep ocean vent communities. This remarkable ecological system is not dependent on sunlight but bacteria, utilising the chemistry of the hot volcanic vents, are at the base of its food chain.
The biosphere contains great quantities of elements such as carbon, nitrogen, hydrogen and oxygen. Other elements, such as phosphorus, calcium, and potassium, are also essential to life, yet are present in smaller amounts. At the ecosystem and biosphere levels, there is a continual recycling of all these elements, which alternate between the mineral and organic states.
While there is a slight input of geothermal energy, the bulk of the functioning of the ecosystem is based on the input of solar energy. Plants and photosynthetic microorganisms convert light into chemical energy by the process of photosynthesis, which creates glucose (a simple sugar) and releases free oxygen. Glucose thus becomes the secondary energy source which drives the ecosystem. Some of this glucose is used directly by other organisms for energy. Other sugar molecules can be converted to other molecules such as amino acids. Plants use some of this sugar, concentrated in nectar to entice pollinators to aid them in reproduction.
Cellular respiration is the process by which organisms (like mammals) break the glucose back down into its constituents, water and carbon dioxide, thus regaining the stored energy the sun originally gave to the plants. The proportion of photosynthetic activity of plants and other photosynthesizers to the respiration of other organisms determines the specific composition of the Earth's atmosphere, particularly its oxygen level. Global air currents mix the atmosphere and maintain nearly the same balance of elements in areas of intense biological activity and areas of slight biological activity.
Water is also exchanged between the hydrosphere, lithosphere, atmosphere and biosphere in regular cycles. The oceans are large tanks, which store water, ensure thermal and climatic stability, as well as the transport of chemical elements thanks to large oceanic currents.
For a better understanding of how the biosphere works, and various dysfunctions related to human activity, American scientists simulated the biosphere in a small-scale model, called Biosphere II.
## The ecosystem concept
Template:Prose
The first principle of ecology is that each living organism has an ongoing and continual relationship with every other element that makes up its environment. An ecosystem can be defined as any situation where there is interaction between organisms and their environment.
The ecosystem is of two entities, the entirety of life, the biocoenosis, and the medium that life exists in, the biotope. Within the ecosystem, species are connected by food chains or food webs. Energy from the sun, captured by primary producers via photosynthesis, flows upward through the chain to primary consumers (herbivores), and then to secondary and tertiary consumers (carnivores and omnivores), before ultimately being lost to the system as waste heat. In the process, matter is incorporated into living organisms, which return their nutrients to the system via decomposition, forming biogeochemical cycles such as the carbon and nitrogen cycles.
The concept of an ecosystem can apply to units of variable size, such as a pond, a field, or a piece of dead wood. An ecosystem within another ecosystem is called a micro ecosystem. For example, an ecosystem can be a stone and all the life under it. A meso ecosystem could be a forest, and a macro ecosystem a whole eco region, with its drainage basin.
The main questions when studying an ecosystem are:
- Whether the colonization of a barren area could be carried out
- Investigation the ecosystem's dynamics and changes
- The methods of which an ecosystem interacts at local, regional and global scale
- Whether the current state is stable
- Investigating the value of an ecosystem and the ways and means that interaction of ecological systems provides benefits to humans, especially in the provision of healthy water.
Ecosystems are often classified by reference to the biotopes concerned. The following ecosystems may be defined:
- As continental ecosystems, such as forest ecosystems, meadow ecosystems such as steppes or savannas, or agro-ecosystems
- As ecosystems of inland waters, such as lentic ecosystems such as lakes or ponds; or lotic ecosystems such as rivers
- As oceanic ecosystems.
Another classification can be done by reference to its communities, such as in the case of an human ecosystem.
## Dynamics and stability
Ecological factors which affect dynamic change in a population or species in a given ecology or environment are usually divided into two groups: abiotic and biotic.
Abiotic factors are geological, geographical, hydrological and climatological parameters. A biotope is an environmentally uniform region characterized by a particular set of abiotic ecological factors. Specific abiotic factors include:
- Water, which is at the same time an essential element to life and a milieu
- Air, which provides oxygen, nitrogen, and carbon dioxide to living species and allows the dissemination of pollen and spores
- Soil, at the same time source of nutriment and physical support
Soil pH, salinity, nitrogen and phosphorus content, ability to retain water, and density are all influential
- Soil pH, salinity, nitrogen and phosphorus content, ability to retain water, and density are all influential
- Temperature, which should not exceed certain extremes, even if tolerance to heat is significant for some species
- Light, which provides energy to the ecosystem through photosynthesis
- Natural disasters can also be considered abiotic
Biocenose, or community, is a group of populations of plants, animals, micro-organisms. Each population is the result of procreations between individuals of same species and cohabitation in a given place and for a given time. When a population consists of an insufficient number of individuals, that population is threatened with extinction; the extinction of a species can approach when all biocenoses composed of individuals of the species are in decline. In small populations, consanguinity (inbreeding) can result in reduced genetic diversity that can further weaken the biocenose.
Biotic ecological factors also influence biocenose viability; these factors are considered as either intraspecific and interspecific relations.
The existing interactions between the various living beings go along with a permanent mixing of mineral and organic substances, absorbed by organisms for their growth, their maintenance and their reproduction, to be finally rejected as waste. These permanent recyclings of the elements (in particular carbon, oxygen and nitrogen) as well as the water are called biogeochemical cycles. They guarantee a durable stability of the biosphere (at least when unchecked human influence and extreme weather or geological phenomena are left aside). This self-regulation, supported by negative feedback controls, ensures the perenniality of the ecosystems. It is shown by the very stable concentrations of most elements of each compartment. This is referred to as homeostasis. The ecosystem also tends to evolve to a state of ideal balance, reached after a succession of events, the climax (for example a pond can become a peat bog).
## Spatial relationships and subdivisions of land
Ecosystems are not isolated from each other, but are interrelated. For example, water may circulate between ecosystems by the means of a river or ocean current. Water itself, as a liquid medium, even defines ecosystems. Some species, such as salmon or freshwater eels move between marine systems and fresh-water systems. These relationships between the ecosystems lead to the concept of a biome.
A biome is a homogeneous ecological formation that exists over a large region as tundra or steppes. The biosphere comprises all of the Earth's biomes -- the entirety of places where life is possible -- from the highest mountains to the depths of the oceans.
Biomes correspond rather well to subdivisions distributed along the latitudes, from the equator towards the poles, with differences based on to the physical environment (for example, oceans or mountain ranges) and to the climate. Their variation is generally related to the distribution of species according to their ability to tolerate temperature and/or dryness. For example, one may find photosynthetic algae only in the photic part of the ocean (where light penetrates), while conifers are mostly found in mountains.
Though this is a simplification of more complicated scheme, latitude and altitude approximate a good representation of the distribution of biodiversity within the biosphere. Very generally, the richness of biodiversity (as well for animal than plant species) is decreasing most rapidly near the equator and less rapidly as one approaches the poles.
The biosphere may also be divided into ecozones, which are very well defined today and primarily follow the continental borders. The ecozones are themselves divided into ecoregions, though there is not agreement on their limits.
## Ecosystem productivity
In an ecosystem, the connections between species are generally related to food and their role in the food chain. There are three categories of organisms:
- Producers -- usually plants which are capable of photosynthesis but could be other organisms such as bacteria around ocean vents that are capable of chemosynthesis.
- Consumers -- animals, which can be primary consumers (herbivorous), or secondary or tertiary consumers (carnivorous and omnivores).
- Decomposers -- bacteria, mushrooms which degrade organic matter of all categories, and restore minerals to the environment. And decomposers can also decompose decaying animals
These relations form sequences, in which each individual consumes the preceding one and is consumed by the one following, in what are called food chains or food network. In a food network, there will be fewer organisms at each level as one follows the links of the network up the chain.
These concepts lead to the idea of biomass (the total living matter in a given place), of primary productivity (the increase in the mass of plants during a given time) and of secondary productivity (the living matter produced by consumers and the decomposers in a given time).
These two last ideas are key, since they make it possible to evaluate the load capacity -- the number of organisms which can be supported by a given ecosystem. In any food network, the energy contained in the level of the producers is not completely transferred to the consumers. And the higher one goes up the chain, the more energy and resources is lost and consumed. Thus, from an energy—and environmental—point of view, it is more efficient for humans to be primary consumers (to subsist from vegetables, grains, legumes, fruit, etc.) than as secondary consumers (from eating herbivores, omnivores, or their products, such as milk, chickens, cattle, sheep, etc.) and still more so than as a tertiary consumer (from consuming carnivores, omnivores, or their products, such as fur, pigs, snakes, alligators, etc.). An ecosystem(s) is unstable when the load capacity is overrun and is especially unstable when a population doesn't have an ecological niche and overconsumers.
The productivity of ecosystems is sometimes estimated by comparing three types of land-based ecosystems and the total of aquatic ecosystems:
- The forests (1/3 of the Earth's land area) contain dense biomasses and are very productive. The total production of the world's forests corresponds to half of the primary production.
- Savannas, meadows, and marshes (1/3 of the Earth's land area) contain less dense biomasses, but are productive. These ecosystems represent the major part of what humans depend on for food.
- Extreme ecosystems in the areas with more extreme climates -- deserts and semi-deserts, tundra, alpine meadows, and steppes -- (1/3 of the Earth's land area) have very sparse biomasses and low productivity
- Finally, the marine and fresh water ecosystems (3/4 of Earth's surface) contain very sparse biomasses (apart from the coastal zones).
Humanity's actions over the last few centuries have seriously reduced the amount of the Earth covered by forests (deforestation), and have increased agro-ecosystems (agriculture). In recent decades, an increase in the areas occupied by extreme ecosystems has occurred (desertification).
## Ecological crisis
Generally, an ecological crisis occurs with the loss of adaptive capacity when the resilience of an environment or of a species or a population evolves in a way unfavourable to coping with perturbations that interfere with that ecosystem, landscape or species survival. It may be that the environment quality degrades compared to the species needs, after a change in an abiotic ecological factor (for example, an increase of temperature, less significant rainfalls). It may be that the environment becomes unfavourable for the survival of a species (or a population) due to an increased pressure of predation (for example overfishing). Lastly, it may be that the situation becomes unfavourable to the quality of life of the species (or the population) due to a rise in the number of individuals (overpopulation).
Ecological crises vary in length and severity, occurring within a few months or taking as long as a few million years. They can also be of natural or anthropic origin. They may relate to one unique species or to many species, as in an Extinction event. Lastly, an ecological crisis may be local (as an oil spill) or global (a rise in the sea level due to global warming).
According to its degree of endemism, a local crisis will have more or less significant consequences, from the death of many individuals to the total extinction of a species. Whatever its origin, disappearance of one or several species often will involve a rupture in the food chain, further impacting the survival of other species.
In the case of a global crisis, the consequences can be much more significant; some extinction events showed the disappearance of more than 90% of existing species at that time. However, it should be noted that the disappearance of certain species, such as the dinosaurs, by freeing an ecological niche, allowed the development and the diversification of the mammals. An ecological crisis thus paradoxically favored biodiversity.
Sometimes, an ecological crisis can be a specific and reversible phenomenon at the ecosystem scale. But more generally, the crises impact will last. Indeed, it rather is a connected series of events, that occur till a final point. From this stage, no return to the previous stable state is possible, and a new stable state will be set up gradually (see homeorhesy).
Lastly, if an ecological crisis can cause extinction, it can also more simply reduce the quality of life of the remaining individuals. Thus, even if the diversity of the human population is sometimes considered threatened (see in particular indigenous people), few people envision human disappearance at short span. However, epidemic diseases, famines, impact on health of reduction of air quality, food crises, reduction of living space, accumulation of toxic or non degradable wastes, threats on keystone species (great apes, panda, whales) are also factors influencing the well-being of people.
Due to the increases in technology and a rapidly increasing population, humans have more influence on their own environment than any other ecosystem engineer.
Some common examples of ecological crises are:
- The Exxon Valdez oil spill off the coast of Alaska in 1989
- Permian-Triassic extinction event 250 million of years ago
- Cretaceous–Tertiary extinction event 65 million years ago
- Global warming related to the Greenhouse effect. Warming could involve flooding of the Asian deltas (see also eco refugees), multiplication of extreme weather phenomena and changes in the nature and quantity of the food resources (see Global warming and agriculture). See also international Kyoto Protocol.
- Ozone layer hole issue
- Deforestation and desertification, with disappearance of many species.
- Volcanic eruptions such as Mount St. Helens and the Tunguska and other impact events
- The nuclear meltdown at Chernobyl in 1986 caused the death of many people and animals from cancer, and caused mutations in a large number of animals and people. The area around the plant is now abandoned by humans because of the large amount of radiation generated by the meltdown. Twenty years after the accident, the animals have returned.
# Bibliography
- Warming, E. (1909) Oecology of Plants - an introduction to the study of plant-communities. Clarendon Press, Oxford.
- Haeckel, E. (1866) General Morphology of Organisms; General Outlines of the Science of Organic Forms based on Mechanical Principles through the Theory of Descent as reformed by Charles Darwin. Berlin. | https://www.wikidoc.org/index.php/Ecological | |
9a527fe47aa7872d20708e5ea1223b27e7cbdfde | wikidoc | Ecthyma | Ecthyma
# Overview
Ecthyma is an ulcerative pyoderma of the skin caused by bacteria such as Pseudomonas (the most common isolate), Streptococcus pyogenes, and Staphylococcus aureus. Because ecthyma extends into the dermis, it is often referred to as a deeper form of impetigo.
# Ecthyma
- Ecthyma is an ulcerative pyoderma of the skin caused by bacteria such as Pseudomonas (the most common isolate), Streptococcus pyogenes, and Staphylococcus aureus. Because ecthyma extends into the dermis, it is often referred to as a deeper form of impetigo.
- Causes include insect bites and an ignored minor trauma. Wound cultures usually reveal that the lesions are teeming with bacteria.
- Ecthyma describes ulcers forming under a crusted surface infection. The site may have been that of an insect bite or of neglected minor trauma. It is treated by antibiotics like cloxacillin, erythromycin, and cephalexin. Pseudomonas infections are often treated with two antibiotics due to frequent resistance.
- Ecthyma has a predilection for children and elderly individuals. Outbreaks have also been reported in young military trainees
- Ecthyma usually arises on the lower extremities of children, persons with diabetes, and neglected elderly patients.
- During wartime in tropical climates, ecthymatous ulcers are commonly found on the ankles and dorsa of the feet.
# Etiology
- Ecthyma can be seen in areas of previously sustained tissue injury (e.g., excoriations, insect bites, dermatitis). Ecthyma can be seen in patients who are immunocompromised (e.g., diabetes, neutropenia, HIV infection).
Important factors contribute to the development of streptococcal pyodermas or ecthyma:
- High temperature and humidity
- Crowded living conditions
- Poor hygiene
- Untreated impetigo that progresses to ecthyma most frequently occurs in patients with poor hygiene.
- Some strains of Streptococcus pyogenes have a high affinity for both pharyngeal mucosa and skin. Pharyngeal colonization of S. pyogenes has been documented in patients with ecthyma.
# Pathophysiology
- Ecthyma begins similarly to superficial impetigo. Group A beta-hemolytic streptococci may initiate the lesion or may secondarily infect preexisting wounds. Preexisting tissue damage (e.g., excoriations, insect bites, dermatitis) and immunocompromised states (e.g., diabetes, neutropenia) predispose patients to the development of ecthyma. Spread of skin streptococci is augmented by crowding and poor hygiene.
- The difference between ecthyma and impetigo is that in impetigo the erosion is at the stratum corneum, while in ecthyma the ulcer is full thickness and thus heals with scarring.
- There is no racial or sexual dominance in Ecthyma.
# Morbidity/Mortality
- Ecthyma rarely leads to systemic symptoms or bacteremia. Lesions are painful and can have associated lymphadenopathy. Secondary lymphangitis and cellulitis can occur. Ecthyma does heal with scarring. The rate of poststreptococcal glomerulonephritis is approximately 1%.
# Treatment
## Antimicrobial Regimen
- Methicillin-Susceptible Staphylococcus Aureus
- Preferred regimen (1): Dicloxacillin 250 mg PO qid for 7 days.
- Preferred regimen (2): Cephalexin 250 mg PO qid for 7 days.
- Methicillin-Resistant Staphylococcus Aureus
- Preferred regimen (1): Doxycycline 100 mg PO bid
- Preferred regimen (2): Clindamycin 600 mg every 8 h IV or 300–450 mg PO qid
- Preferred regimen (3): Sulfamethoxazole-trimethoprim 25–40 mg/kg/d in 3 divided doses IV or 25–30 mg/kg/d in 3 divided doses PO | Ecthyma
Template:Seealso
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Ecthyma is an ulcerative pyoderma of the skin caused by bacteria such as Pseudomonas (the most common isolate), Streptococcus pyogenes, and Staphylococcus aureus. Because ecthyma extends into the dermis, it is often referred to as a deeper form of impetigo.
# Ecthyma
- Ecthyma is an ulcerative pyoderma of the skin caused by bacteria such as Pseudomonas (the most common isolate), Streptococcus pyogenes, and Staphylococcus aureus. Because ecthyma extends into the dermis, it is often referred to as a deeper form of impetigo.
- Causes include insect bites and an ignored minor trauma. Wound cultures usually reveal that the lesions are teeming with bacteria.
- Ecthyma describes ulcers forming under a crusted surface infection. The site may have been that of an insect bite or of neglected minor trauma. It is treated by antibiotics like cloxacillin, erythromycin, and cephalexin. Pseudomonas infections are often treated with two antibiotics due to frequent resistance.
- Ecthyma has a predilection for children and elderly individuals. Outbreaks have also been reported in young military trainees
- Ecthyma usually arises on the lower extremities of children, persons with diabetes, and neglected elderly patients.
- During wartime in tropical climates, ecthymatous ulcers are commonly found on the ankles and dorsa of the feet.
# Etiology
- Ecthyma can be seen in areas of previously sustained tissue injury (e.g., excoriations, insect bites, dermatitis). Ecthyma can be seen in patients who are immunocompromised (e.g., diabetes, neutropenia, HIV infection).
Important factors contribute to the development of streptococcal pyodermas or ecthyma:
- High temperature and humidity
- Crowded living conditions
- Poor hygiene
- Untreated impetigo that progresses to ecthyma most frequently occurs in patients with poor hygiene.
- Some strains of Streptococcus pyogenes have a high affinity for both pharyngeal mucosa and skin. Pharyngeal colonization of S. pyogenes has been documented in patients with ecthyma.
# Pathophysiology
- Ecthyma begins similarly to superficial impetigo. Group A beta-hemolytic streptococci may initiate the lesion or may secondarily infect preexisting wounds. Preexisting tissue damage (e.g., excoriations, insect bites, dermatitis) and immunocompromised states (e.g., diabetes, neutropenia) predispose patients to the development of ecthyma. Spread of skin streptococci is augmented by crowding and poor hygiene.
- The difference between ecthyma and impetigo is that in impetigo the erosion is at the stratum corneum, while in ecthyma the ulcer is full thickness and thus heals with scarring.
- There is no racial or sexual dominance in Ecthyma.
# Morbidity/Mortality
- Ecthyma rarely leads to systemic symptoms or bacteremia. Lesions are painful and can have associated lymphadenopathy. Secondary lymphangitis and cellulitis can occur. Ecthyma does heal with scarring. The rate of poststreptococcal glomerulonephritis is approximately 1%.
# Treatment
## Antimicrobial Regimen
- Methicillin-Susceptible Staphylococcus Aureus
- Preferred regimen (1): Dicloxacillin 250 mg PO qid for 7 days.
- Preferred regimen (2): Cephalexin 250 mg PO qid for 7 days.
- Methicillin-Resistant Staphylococcus Aureus
- Preferred regimen (1): Doxycycline 100 mg PO bid
- Preferred regimen (2): Clindamycin 600 mg every 8 h IV or 300–450 mg PO qid
- Preferred regimen (3): Sulfamethoxazole-trimethoprim 25–40 mg/kg/d in 3 divided doses IV or 25–30 mg/kg/d in 3 divided doses PO | https://www.wikidoc.org/index.php/Ecthyma | |
892abf6a63998c92b00cd9a71c7b7c227418a8e2 | wikidoc | Ectopia | Ectopia
# Overview
In medicine an ectopia is a displacement or malposition of an organ of the body. Most ectopias are congenital but some may happen later in life.
- Ectopia lentis is the displacement of the crystalline lens of the eye
- Ectopia cordis is the displacement of the heart outside the body during fetal development
- Renal ectopia occurs when both kidneys occur on the same side of the body
- Ectopic pregnancy occurs when the fertilized egg implants anywhere other than the uterine wall
- Cardiac ectopy occurs when electrical signals for a heartbeat originate in the wrong part of the heart muscle.
In molecular biology a gene is ectopically expressed when it is expressed in an abnormal place.
da:Ektopi
de:Ektopie
it:Ectopia | Ectopia
# Overview
In medicine an ectopia is a displacement or malposition of an organ of the body. Most ectopias are congenital but some may happen later in life.
- Ectopia lentis is the displacement of the crystalline lens of the eye
- Ectopia cordis is the displacement of the heart outside the body during fetal development
- Renal ectopia occurs when both kidneys occur on the same side of the body
- Ectopic pregnancy occurs when the fertilized egg implants anywhere other than the uterine wall
- Cardiac ectopy occurs when electrical signals for a heartbeat originate in the wrong part of the heart muscle.
In molecular biology a gene is ectopically expressed when it is expressed in an abnormal place.
Template:WikiDoc Sources
da:Ektopi
de:Ektopie
it:Ectopia | https://www.wikidoc.org/index.php/Ectopia | |
16f38b22f81397309337490260370e4883a2b463 | wikidoc | Eglonyl | Eglonyl
Eglonyl is the name of medicine produced by Alkaloid (Skopje, Macedonia), under license from Sanofi Synthelabo, France.
The active susbtance in Eglonyl is sulpiride which works by blocking dopamine receptors in the brain. The medicine is used to treat schizophrenia and depression.
Eglonyl can be used to booster milk production in lactating women, due to its prolactin stimulating side effect. | Eglonyl
Eglonyl is the name of medicine produced by Alkaloid (Skopje, Macedonia), under license from Sanofi Synthelabo, France.
The active susbtance in Eglonyl is sulpiride which works by blocking dopamine receptors in the brain. The medicine is used to treat schizophrenia and depression.
Eglonyl can be used to booster milk production[1] in lactating women, due to its prolactin stimulating side effect. | https://www.wikidoc.org/index.php/Eglonyl | |
34eb340d6d14588925741919c183d3c7674d1b8c | wikidoc | Elastin | Elastin
Elastin is a highly elastic protein in connective tissue and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of vertebrates and used in places where mechanical energy is required to be stored. In humans, elastin is encoded by the ELN gene.
# Function
The ELN gene encodes a protein that is one of the two components of elastic fibers. The encoded protein is rich in hydrophobic amino acids such as glycine and proline, which form mobile hydrophobic regions bounded by crosslinks between lysine residues. Multiple transcript variants encoding different isoforms have been found for this gene. Elastin's soluble precursor is tropoelastin. The characterization of disorder is consistent with an entropy-driven mechanism of elastic recoil. It is concluded that conformational disorder is a constitutive feature of elastin structure and function.
# Clinical significance
Deletions and mutations in this gene are associated with supravalvular aortic stenosis (SVAS) and the autosomal dominant cutis laxa. Other associated defects in elastin include Marfan syndrome, emphysema caused by α1-antitrypsin deficiency, atherosclerosis, Buschke-Ollendorff syndrome, Menkes syndrome, pseudoxanthoma elasticum, and Williams syndrome.
# Composition
In the body, elastin is usually associated with other proteins in connective tissues. Elastic fiber in the body is a mixture of amorphous elastin and fibrous fibrillin. Both components are primarily made of smaller amino acids such as glycine, valine, alanine, and proline. The total elastin ranges from 58 to 75% of the weight of the dry defatted artery in normal canine arteries. Comparison between fresh and digested tissues shows that, at 35% strain, a minimum of 48% of the arterial load is carried by elastin, and a minimum of 43% of the change in stiffness of arterial tissue is due to the change in elastin stiffness.
## Tissue distribution
Elastin serves an important function in arteries as a medium for pressure wave propagation to help blood flow and is particularly abundant in large elastic blood vessels such as the aorta. Elastin is also very important in the lungs, elastic ligaments, elastic cartilage, the skin, and the bladder. It is present in all vertebrates above the jawless fish.
# Biosynthesis
## Tropoelastin precursors
Elastin is made by linking together many small soluble precursor tropoelastin protein molecules (50-70 kDa), to make the final massive insoluble, durable complex. The unlinked tropoelastin molecules are not normally available in the cell, since they become crosslinked into elastin fibres immediately after their synthesis by the cell and during their export into the extracellular matrix.
Each tropoelastin consists of a string of 36 small domains, each weighing about 2 kDa in a random coil conformation. The protein consists of alternating hydrophobic and hydrophilic domains, which are encoded by separate exons, so that the domain structure of tropoelastin reflects the exon organization of the gene. The hydrophilic domains contain Lys-Ala (KA) and Lys-Pro (KP) motifs that are involved in crosslinking during the formation of mature elastin. In the KA domains, lysine residues occur as pairs or triplets separated by two or three alanine residues (e.g. AAAKAAKAA) whereas in KP domains the lysine residues are separated mainly by proline residues (e.g. KPLKP).
## Aggregation
Tropoelastin aggregates at physiological temperature due to interactions between hydrophobic domains in a process called coacervation. This process is reversible and thermodynamically controlled and does not require protein cleavage. The coacervate is made insoluble by irreversible crosslinking.
## Crosslinking
To make mature elastin fibres, the tropoelastin molecules are cross-linked via their lysine residues with desmosine and isodesmosine cross-linking molecules. The enzyme that performs the crosslinking is lysyl oxidase, using an in vivo Chichibabin pyridine synthesis reaction.
# Molecular biology
In mammals, the genome only contains one gene for tropoelastin, called ELN. The human ELN gene is a 45 kb segment on chromosome 7, and has 34 exons interrupted by almost 700 introns, with the first exon being a signal peptide assigning its extracellular localization. The large number of introns suggests that genetic recombination may contribute to the instability of the gene, leading to diseases such as SVAS. The expression of tropoelastin mRNA is highly regulated under at least eight different transcription start sites.
Tissue specific variants of elastin are produced by alternative splicing of the tropoelastin gene. There are at least 11 known human tropoelastin isoforms. these isoforms are under developmental regulation, however there are minimal differences among tissues at the same developmental stage. | Elastin
Elastin is a highly elastic protein in connective tissue and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of vertebrates and used in places where mechanical energy is required to be stored. In humans, elastin is encoded by the ELN gene.[1]
# Function
The ELN gene encodes a protein that is one of the two components of elastic fibers. The encoded protein is rich in hydrophobic amino acids such as glycine and proline, which form mobile hydrophobic regions bounded by crosslinks between lysine residues.[2] Multiple transcript variants encoding different isoforms have been found for this gene.[2] Elastin's soluble precursor is tropoelastin.[3] The characterization of disorder is consistent with an entropy-driven mechanism of elastic recoil. It is concluded that conformational disorder is a constitutive feature of elastin structure and function.[4]
# Clinical significance
Deletions and mutations in this gene are associated with supravalvular aortic stenosis (SVAS) and the autosomal dominant cutis laxa.[2] Other associated defects in elastin include Marfan syndrome, emphysema caused by α1-antitrypsin deficiency, atherosclerosis, Buschke-Ollendorff syndrome, Menkes syndrome, pseudoxanthoma elasticum, and Williams syndrome.[5]
# Composition
In the body, elastin is usually associated with other proteins in connective tissues. Elastic fiber in the body is a mixture of amorphous elastin and fibrous fibrillin. Both components are primarily made of smaller amino acids such as glycine, valine, alanine, and proline.[5][6] The total elastin ranges from 58 to 75% of the weight of the dry defatted artery in normal canine arteries.[7] Comparison between fresh and digested tissues shows that, at 35% strain, a minimum of 48% of the arterial load is carried by elastin, and a minimum of 43% of the change in stiffness of arterial tissue is due to the change in elastin stiffness.[8]
## Tissue distribution
Elastin serves an important function in arteries as a medium for pressure wave propagation to help blood flow and is particularly abundant in large elastic blood vessels such as the aorta. Elastin is also very important in the lungs, elastic ligaments, elastic cartilage, the skin, and the bladder. It is present in all vertebrates above the jawless fish.[9]
# Biosynthesis
## Tropoelastin precursors
Elastin is made by linking together many small soluble precursor tropoelastin protein molecules (50-70 kDa), to make the final massive insoluble, durable complex. The unlinked tropoelastin molecules are not normally available in the cell, since they become crosslinked into elastin fibres immediately after their synthesis by the cell and during their export into the extracellular matrix.
Each tropoelastin consists of a string of 36 small domains, each weighing about 2 kDa in a random coil conformation. The protein consists of alternating hydrophobic and hydrophilic domains, which are encoded by separate exons, so that the domain structure of tropoelastin reflects the exon organization of the gene. The hydrophilic domains contain Lys-Ala (KA) and Lys-Pro (KP) motifs that are involved in crosslinking during the formation of mature elastin. In the KA domains, lysine residues occur as pairs or triplets separated by two or three alanine residues (e.g. AAAKAAKAA) whereas in KP domains the lysine residues are separated mainly by proline residues (e.g. KPLKP).
## Aggregation
Tropoelastin aggregates at physiological temperature due to interactions between hydrophobic domains in a process called coacervation. This process is reversible and thermodynamically controlled and does not require protein cleavage. The coacervate is made insoluble by irreversible crosslinking.
## Crosslinking
To make mature elastin fibres, the tropoelastin molecules are cross-linked via their lysine residues with desmosine and isodesmosine cross-linking molecules. The enzyme that performs the crosslinking is lysyl oxidase, using an in vivo Chichibabin pyridine synthesis reaction.[10]
# Molecular biology
In mammals, the genome only contains one gene for tropoelastin, called ELN. The human ELN gene is a 45 kb segment on chromosome 7, and has 34 exons interrupted by almost 700 introns, with the first exon being a signal peptide assigning its extracellular localization. The large number of introns suggests that genetic recombination may contribute to the instability of the gene, leading to diseases such as SVAS. The expression of tropoelastin mRNA is highly regulated under at least eight different transcription start sites.
Tissue specific variants of elastin are produced by alternative splicing of the tropoelastin gene. There are at least 11 known human tropoelastin isoforms. these isoforms are under developmental regulation, however there are minimal differences among tissues at the same developmental stage.[5] | https://www.wikidoc.org/index.php/Elastin | |
cd99bcb8cdbfcb3df973108eae67865aa6b6876f | wikidoc | Ellipse | Ellipse
In mathematics, an ellipse (from the Greek ἔλλειψις, literally absence) is a locus of points in a plane such that the sum of the distances to two fixed points is a constant. The two fixed points are called foci (plural of focus). An alternate definition would be that an ellipse is the path traced out by a point whose distance from a fixed point, called focus, maintains a constant ratio less than one with its distance from a straight line not passing through the focus, called the directrix.
# Overview
An ellipse is a type of conic section: if a conical surface is cut with a plane which does not intersect the cone's base, the intersection of the cone and plane is an ellipse. For a short elementary proof of this, see Dandelin spheres.
Algebraically, an ellipse is a curve in the Cartesian plane defined by
an equation of the form
such that B^2 , where all of the coefficients are real, and where more than one solution, defining a pair of points (x, y) on the ellipse, exists.
An ellipse can be drawn with two pins, a loop of string, and a pencil. The pins are placed at the foci and the pins and pencil are enclosed inside the string. The pencil is placed on the paper inside the string, so the string is taut. The string will form a triangle. If the pencil is moved around so that the string stays taut, the sum of the distances from the pencil to the pins will remain constant, satisfying the definition of an ellipse.
The line segment AB, that passes through the foci and terminates on the ellipse, is called the major axis. The major axis is the longest segment that can be obtained by joining two points on the ellipse. The line segment CD, which passes through the center (halfway between the foci), perpendicular to the major axis, and terminates on the ellipse, is called the minor axis. The semimajor axis (denoted by a in the figure) is one half the major axis: the line segment from the center, through a focus, and to the edge of the ellipse. Likewise, the semiminor axis (denoted by b in the figure) is one half the minor axis.
If the two foci coincide, then the ellipse is a circle; in other words, a circle is a special case of an ellipse, one where the eccentricity is zero.
An ellipse centered at the origin can be viewed as the image of the unit circle under a linear map associated with a symmetric matrix A = PDP^T, D being a diagonal matrix with the eigenvalues of A, both of which are real positive, along the main diagonal, and P being a real unitary matrix having as columns the eigenvectors of A. Then the axes of the ellipse will lie along the eigenvectors of A, and the eigenvalues are the lengths of the semimajor and semiminor axes.
An ellipse can be produced by multiplying the x coordinates of all points on a circle by a constant, without changing the y coordinates. This is equivalent to stretching the circle out in the x-direction.
# Eccentricity
The shape of an ellipse can be expressed by a number called the eccentricity of the ellipse, conventionally denoted \, \varepsilon. The eccentricity is a non-negative number less than 1 and greater than or equal to 0. It is the value of the constant ratio of the distance of a point on an ellipse from a focus to that from the corresponding directrix. An eccentricity of 0 implies that the two foci occupy the same point and that the ellipse is a circle.
For an ellipse with semimajor axis a and semiminor axis b,
the eccentricity is
The greater the eccentricity is, the larger the ratio of a to b, and therefore the more elongated the ellipse.
If c equals the distance from the center to either focus, then
The distance c is known as the linear eccentricity of the ellipse. The distance between the foci is 2aε.
# Equations
An ellipse with a semimajor axis a and semiminor axis b, centered at the point (h,k) and having its major axis parallel to the x-axis may be specified by the equation
This ellipse can be expressed parametrically as
where t may be restricted to the interval -\pi\leq t \leq \pi\,\!.
If h = 0 and k = 0 (i.e., if the center is the origin (0,0)), then we can express this ellipse in polar coordinates by the
equation
where \varepsilon is the eccentricity of the ellipse.
With one focus at the origin, the ellipse's polar equation is
A Gauss-mapped form:
has normal (\cos\beta,\sin\beta).
# Semi-latus rectum and polar coordinates
The semi-latus rectum of an ellipse, usually denoted l\,\! (lowercase L), is the distance from a focus of the ellipse to the ellipse itself, measured along a line perpendicular to the major axis. It is related to a\,\! and b\,\! (the ellipse's semi-axes) by the formula al=b^2\,\! or, if using the eccentricity, l=a\cdot(1-\varepsilon^2)\,\!.
In polar coordinates, an ellipse with one focus at the origin and the other on the negative x-axis is given by the equation
An ellipse can also be thought of as a projection of a circle: a circle on a plane at angle φ to the horizontal projected vertically onto a horizontal plane gives an ellipse of eccentricity sin φ, provided φ is not 92°.
# Area and circumference
The area enclosed by an ellipse is πab, where (as before) a and b are the ellipse's semimajor and semiminor axes.
The circumference C of an ellipse is 4 a E(\varepsilon),
where the function E is the complete elliptic integral of the second kind.
The exact infinite series is:
Or:
A good approximation is Ramanujan's:
which can also be written as:
For the special case where the minor axis is half the major axis, we get:
-r
C \approx \frac{a}{2} \sqrt{93 + \frac{1}{2} \sqrt{3}} \!\, (better approximation).
More generally, the arc length of a portion of the circumference, as a function of the angle subtended, is given by an incomplete elliptic integral. The inverse function, the angle subtended as a function of the arc length, is given by the elliptic functions.
# Stretching and projection
An ellipse may be uniformly stretched along any axis, in or out of the plane of the ellipse, and it will still be an ellipse. The stretched ellipse will have different properties (perhaps changed eccentricity and semi-major axis length, for instance), but it will still be an ellipse (or a degenerate ellipse: a circle or a line). Similarly, any oblique projection onto a plane results in a conic section. If the projection is a closed curve on the plane, then the curve is an ellipse or a degenerate ellipse.
# Reflection property
Assume an elliptic mirror with a light source at one of the foci. Then all rays are reflected to a single point — the second focus. Since no other curve has such a property, it can be used as an alternative definition of an ellipse. In a circle, all light would be reflected back to the center since all tangents are orthogonal to the radius.
Sound waves are reflected in a similar way, so in a large elliptical room a person standing at one focus can hear a person standing at another focus remarkably well. Such a room is called a whisper chamber. Examples are the National Statuary Hall Collection at the U.S. Capitol (where John Quincy Adams is said to have used this property for eavesdropping on political matters), at an exhibit on sound at the Museum of Science and Industry in Chicago, in front of the University of Illinois at Urbana-Champaign Foellinger Auditorium, and also at a side chamber of the Palace of Charles V, in the Alhambra.
# Ellipses in physics
In the 17th century, Johannes Kepler explained that the orbits along which the planets travel around the Sun are ellipses in his first law of planetary motion. Later, Isaac Newton explained this as a corollary of his law of universal gravitation.
More generally, in the gravitational two-body problem, if the two bodies are bound to each other (i.e., the total energy is negative), their orbits are similar ellipses with the common barycenter being one of the foci of each ellipse. The other focus of either ellipse has no known physical significance. Interestingly, the orbit of either body in the reference frame of the other is also an ellipse, with the other body at one focus.
The general solution for a harmonic oscillator in two or more dimensions is also an ellipse, but this time with the origin of the force located at the center of the ellipse.
In optics, an index ellipsoid describes the refractive index of a material as a function of the direction through that material. This only applies to materials that are optically anisotropic. Also see birefringence.
# Ellipses in computer graphics
Drawing an ellipse is a common graphics primitive in standard display libraries, such as the Macintosh QuickDraw API, the Windows Graphics Device Interface (GDI) and the Windows Presentation Foundation (WPF). Often such libraries are limited and can only draw an ellipse with either the major axis or the minor axis horizontal. Jack Bresenham at IBM is most famous for the invention of 2D drawing primitives, including line and circle drawing, using only fast integer operations such as addition and branch on carry bit. An efficient generalization to draw ellipses was invented in 1984 by Jerry Van Aken (IEEE CG&A, Sept. 1984).
The following is an example JavaScript code used to calculate the points of an ellipse.
- This functions returns an array containing 36 points to draw an
- ellipse.
- @param x {double} X coordinate
- @param y {double} Y coordinate
- @param a {double} Semimajor axis
- @param b {double} Semiminor axis
- @param angle {double} Angle of the ellipse
function calculateEllipse(x, y, a, b, angle, steps) | Ellipse
In mathematics, an ellipse (from the Greek ἔλλειψις, literally absence) is a locus of points in a plane such that the sum of the distances to two fixed points is a constant. The two fixed points are called foci (plural of focus). An alternate definition would be that an ellipse is the path traced out by a point whose distance from a fixed point, called focus, maintains a constant ratio less than one with its distance from a straight line not passing through the focus, called the directrix.
# Overview
An ellipse is a type of conic section: if a conical surface is cut with a plane which does not intersect the cone's base, the intersection of the cone and plane is an ellipse. For a short elementary proof of this, see Dandelin spheres.
Algebraically, an ellipse is a curve in the Cartesian plane defined by
an equation of the form
such that <math>B^2 < 4 AC</math>, where all of the coefficients are real, and where more than one solution, defining a pair of points (x, y) on the ellipse, exists.
An ellipse can be drawn with two pins, a loop of string, and a pencil. The pins are placed at the foci and the pins and pencil are enclosed inside the string. The pencil is placed on the paper inside the string, so the string is taut. The string will form a triangle. If the pencil is moved around so that the string stays taut, the sum of the distances from the pencil to the pins will remain constant, satisfying the definition of an ellipse.
The line segment AB, that passes through the foci and terminates on the ellipse, is called the major axis. The major axis is the longest segment that can be obtained by joining two points on the ellipse. The line segment CD, which passes through the center (halfway between the foci), perpendicular to the major axis, and terminates on the ellipse, is called the minor axis. The semimajor axis (denoted by a in the figure) is one half the major axis: the line segment from the center, through a focus, and to the edge of the ellipse. Likewise, the semiminor axis (denoted by b in the figure) is one half the minor axis.
If the two foci coincide, then the ellipse is a circle; in other words, a circle is a special case of an ellipse, one where the eccentricity is zero.
An ellipse centered at the origin can be viewed as the image of the unit circle under a linear map associated with a symmetric matrix <math>A = PDP^T</math>, <math>D</math> being a diagonal matrix with the eigenvalues of <math>A</math>, both of which are real positive, along the main diagonal, and <math>P</math> being a real unitary matrix having as columns the eigenvectors of <math>A</math>. Then the axes of the ellipse will lie along the eigenvectors of <math>A</math>, and the eigenvalues are the lengths of the semimajor and semiminor axes.
An ellipse can be produced by multiplying the x coordinates of all points on a circle by a constant, without changing the y coordinates. This is equivalent to stretching the circle out in the x-direction.
# Eccentricity
The shape of an ellipse can be expressed by a number called the eccentricity of the ellipse, conventionally denoted <math>\, \varepsilon</math>. The eccentricity is a non-negative number less than 1 and greater than or equal to 0. It is the value of the constant ratio of the distance of a point on an ellipse from a focus to that from the corresponding directrix. An eccentricity of 0 implies that the two foci occupy the same point and that the ellipse is a circle.
For an ellipse with semimajor axis a and semiminor axis b,
the eccentricity is
The greater the eccentricity is, the larger the ratio of a to b, and therefore the more elongated the ellipse.
If c equals the distance from the center to either focus, then
The distance c is known as the linear eccentricity of the ellipse. The distance between the foci is 2aε.
# Equations
An ellipse with a semimajor axis a and semiminor axis b, centered at the point <math>(h,k)</math> and having its major axis parallel to the x-axis may be specified by the equation
This ellipse can be expressed parametrically as
where <math>t</math> may be restricted to the interval <math>-\pi\leq t \leq \pi\,\!</math>.
If <math>h</math> = 0 and <math>k</math> = 0 (i.e., if the center is the origin (0,0)), then we can express this ellipse in polar coordinates by the
equation
where <math>\varepsilon</math> is the eccentricity of the ellipse.
With one focus at the origin, the ellipse's polar equation is
A Gauss-mapped form:
has normal <math>(\cos\beta,\sin\beta)</math>.
# Semi-latus rectum and polar coordinates
The semi-latus rectum of an ellipse, usually denoted <math>l\,\!</math> (lowercase L), is the distance from a focus of the ellipse to the ellipse itself, measured along a line perpendicular to the major axis. It is related to <math>a\,\!</math> and <math>b\,\!</math> (the ellipse's semi-axes) by the formula <math>al=b^2\,\!</math> or, if using the eccentricity, <math>l=a\cdot(1-\varepsilon^2)\,\!</math>.
In polar coordinates, an ellipse with one focus at the origin and the other on the negative x-axis is given by the equation
An ellipse can also be thought of as a projection of a circle: a circle on a plane at angle φ to the horizontal projected vertically onto a horizontal plane gives an ellipse of eccentricity sin φ, provided φ is not 92°.
# Area and circumference
The area enclosed by an ellipse is πab, where (as before) a and b are the ellipse's semimajor and semiminor axes.
The circumference <math>C</math> of an ellipse is <math>4 a E(\varepsilon)</math>,
where the function <math>E</math> is the complete elliptic integral of the second kind.
The exact infinite series is:
Or:
A good approximation is Ramanujan's:
which can also be written as:
For the special case where the minor axis is half the major axis, we get:
or
<math>C \approx \frac{a}{2} \sqrt{93 + \frac{1}{2} \sqrt{3}} \!\,</math> (better approximation).
More generally, the arc length of a portion of the circumference, as a function of the angle subtended, is given by an incomplete elliptic integral. The inverse function, the angle subtended as a function of the arc length, is given by the elliptic functions.
# Stretching and projection
An ellipse may be uniformly stretched along any axis, in or out of the plane of the ellipse, and it will still be an ellipse. The stretched ellipse will have different properties (perhaps changed eccentricity and semi-major axis length, for instance), but it will still be an ellipse (or a degenerate ellipse: a circle or a line). Similarly, any oblique projection onto a plane results in a conic section. If the projection is a closed curve on the plane, then the curve is an ellipse or a degenerate ellipse.
# Reflection property
Assume an elliptic mirror with a light source at one of the foci. Then all rays are reflected to a single point — the second focus. Since no other curve has such a property, it can be used as an alternative definition of an ellipse. In a circle, all light would be reflected back to the center since all tangents are orthogonal to the radius.
Sound waves are reflected in a similar way, so in a large elliptical room a person standing at one focus can hear a person standing at another focus remarkably well. Such a room is called a whisper chamber. Examples are the National Statuary Hall Collection at the U.S. Capitol (where John Quincy Adams is said to have used this property for eavesdropping on political matters), at an exhibit on sound at the Museum of Science and Industry in Chicago, in front of the University of Illinois at Urbana-Champaign Foellinger Auditorium, and also at a side chamber of the Palace of Charles V, in the Alhambra.
# Ellipses in physics
In the 17th century, Johannes Kepler explained that the orbits along which the planets travel around the Sun are ellipses in his first law of planetary motion. Later, Isaac Newton explained this as a corollary of his law of universal gravitation.
More generally, in the gravitational two-body problem, if the two bodies are bound to each other (i.e., the total energy is negative), their orbits are similar ellipses with the common barycenter being one of the foci of each ellipse. The other focus of either ellipse has no known physical significance. Interestingly, the orbit of either body in the reference frame of the other is also an ellipse, with the other body at one focus.
The general solution for a harmonic oscillator in two or more dimensions is also an ellipse, but this time with the origin of the force located at the center of the ellipse.
In optics, an index ellipsoid describes the refractive index of a material as a function of the direction through that material. This only applies to materials that are optically anisotropic. Also see birefringence.
# Ellipses in computer graphics
Drawing an ellipse is a common graphics primitive in standard display libraries, such as the Macintosh QuickDraw API, the Windows Graphics Device Interface (GDI) and the Windows Presentation Foundation (WPF). Often such libraries are limited and can only draw an ellipse with either the major axis or the minor axis horizontal. Jack Bresenham at IBM is most famous for the invention of 2D drawing primitives, including line and circle drawing, using only fast integer operations such as addition and branch on carry bit. An efficient generalization to draw ellipses was invented in 1984 by Jerry Van Aken (IEEE CG&A, Sept. 1984).
The following is an example JavaScript code used to calculate the points of an ellipse.
<source lang="javascript">
/**
- This functions returns an array containing 36 points to draw an
- ellipse.
-
- @param x {double} X coordinate
- @param y {double} Y coordinate
- @param a {double} Semimajor axis
- @param b {double} Semiminor axis
- @param angle {double} Angle of the ellipse
- /
function calculateEllipse(x, y, a, b, angle, steps)
{
}
</source> | https://www.wikidoc.org/index.php/Ellipse | |
463ef114dee6e5dc28b8deb51fbc35b22f8d7af8 | wikidoc | EmDrive | EmDrive
EmDrive (also Relativity Drive) is the name of a spacecraft propulsion system proposed, and reportedly developed, by Roger Shawyer. New Scientist ran a cover story on EmDrive in its September 8, 2006 issue. The device is a Magnetron with a specially shaped fully enclosed tapering resonator cavity whose area is greater at one end. The inventor claims that the device generates thrust even though no detectable energy leaves the device. The inventor proposes to use it as a spacecraft propulsion system that uses no fuel (other than electricity).
On his homepage the inventor claims that independent peer-review is underway, but so far no publication is available.
The device's operation as described seemingly violates several basic laws of physics, notably conservation of momentum, though the inventor insists to the contrary. John Costella, an expert in relativistic electrodynamics describes the EmDrive as a 'fraud'.
# Principle of operation
The device exploits an idea first suggested by Allen Cullen in the 1950's, an electrical engineer then at University College London, that involves forces created by reflecting microwaves between opposite walls of a cavity. The "idea" is to try to design a cavity in such a manner that forces on one side are greater than the other.
The drive comprises a resonant cavity flooded with microwave radiation. The radiation exerts radiation pressure on the walls of the cavity, and normal Newtonian mechanics would indicate that, no matter what shape the cavity is, the forces exerted upon it from within must balance to zero. Shawyer claims that relativistic effects cause a cavity shaped like a truncated cone to experience a larger force against the large end than the small end, due to the group velocity of the wave changing as the local diameter of the cavity varies.
The increased confinement of the tapered end of the cone leads to a higher effective propagation constant (phase velocity). It also leads to local reflections which account for the apparent force imbalance when considering only the end walls. However, since it is the phase of the light rather than the actual photons bouncing off the walls, each force acts quasi independently from another - much like in a ring laser gyroscope where the beams act as if having an external frame of reference (which they have, since the speed of light is constant). The same principle applies to the EmDrive.
No microwaves or anything else are allowed to leave the device. Since nothing leaves the drive for propulsive purposes an EmDrive can be classed as a reactionless drive. Thus the principle by which the EmDrive is supposed to operate seems to violate conservation of momentum. It is known that the physics equations describing microwaves, Maxwell's equations, conserve momentum, and this would seem to cast doubt on Shawyer's derivation of a thrust effect. In his paper (attached), Shawyer thus takes the following view: any thrust extracted from his device is directly withdrawn from the energy stored in his cavity (due to the Q reflections an average wave encounters when inserted into the cavity, the energy levels quickly build up). In other words: the apparent force on the wider diameter of the cone seems to wane. The extent to which that happens perfectly matches the amount predicted by the law of conservation of momentum.
# Criticism
The EmDrive was the cover story for the September 8, 2006 issue of New Scientist.
After receiving criticism that no peer-reviewed publications on the subject had been made, Mr. Shawyer submitted a theory paper to New Scientist (which is not a peer reviewed scientific journal) Shawyer's paper was almost immediately challenged by Dr. John Costella, a theoretical physicist and electrical engineer who works for the Australian Department of Defence, whose Ph.D. is in relativistic electrodynamics, the field of physics that Mr. Shawyer relies on to support his theory.
# Prototypes and tests
In September 2006 it was reported that Shawyer had constructed a prototype unit weighing 9 kilogrammes that consumes 700 watts of power and produces 88 millinewtons of force.
In May 2007 Eureka magazine reported that a second unit has been built for demonstration purposes, weighing 100 kilogrammes, consuming 300 watts for microwave production (and an unspecified amount for ancillary purposes such as cooling) and producing 9.8 grams (96.1 millinewtons) of force during testing in October 2006. Unlike the prototype unit, which can only be run for short periods before burning out its magnetron, the demonstration unit can be run continuously.
The limiting factor for performance is claimed to be the Q factor of the cavity, as microwave energy lost to heating the cavity reduces the field strength within, so Shawyer is experimenting with a cavity lined in a superconducting material that may produce Q factors sufficient to build a device capable of generating 30 newtons per watt.
These results have neither been reproduced by other scientists or engineers, nor have they been published in a peer-reviewed scientific journal.
# New Scientist article
EmDrive was featured on the cover of issue 2568 of New Scientist, a weekly science magazine. The article portrayed the device as plausible, and emphasized the arguments of those who held that point of view, although it did quote one engineer as saying "it's a load of bloody rubbish." The article included the following arguments from proponents of the theory:
- With a grant from the UK government's Department of Trade and Industry of £250,000, (actually two grants; one a feasibility study of £45,000 and a second of £81,000 to build a demonstration engine - source SPR Ltd.) a commercial regulatory and support agency, Shawyer has built two prototypes that reportedly produce 16mN and 300mN of thrust respectively; each using 1kW of electrical power. A condition of the funding was independent analysis, which was recently completed by John Spiller who says "The thruster's design is practical and could be adapted fairly easily to work in outer space". Shawyer claims that he has been visited by representatives from China and the US Air Force, but ESA has not yet shown much interest. He estimates that his design could save the aerospace community $15 billion over the next ten years.
- Engineers in Germany have created superconducting resonators (for use in particle accelerators) with Q values of several billion, which Shawyer claims would equate to a thrust of 30kN per kilowatt, "enough to lift a large car". Shawyer states that the thruster works best while stationary relative to their thrust.
New Scientist has drawn great criticism from the scientific community due to the uncritical treatment of EmDrive in its article. Science fiction writer Greg Egan distributed a public letter stating that "a sensationalist bent and a lack of basic knowledge by its writers" was making the magazine's coverage sufficiently unreliable "to constitute a real threat to the public understanding of science". In particular, Egan found himself "gobsmacked by the level of scientific illiteracy" in the magazine's coverage of the EmDrive, where New Scientist allowed the publication of "meaningless double-talk" designed to bypass a fatal objection to Sawyer's proposed space drive, namely that it violates the conservation of momentum. Egan urged those reading his letter to write to New Scientist and pressure the magazine to raise its standards, instead of "squandering the opportunity that the magazine's circulation and prestige provides" for genuine science education. The letter was endorsed by mathematical physicist John C. Baez and posted on his blog.
Egan has also recommended that New Scientist publish Costella's refutation of Shawyer's theory paper.
# Analysis
Any claim of a reactionless drive is treated with skepticism by the physics community, since it violates well-established principles such as the conservation of momentum and conservation of energy, both of which have enormous experimental support.
Since there are no known phenomena that do not conserve energy, any calculation based on standard physical theory that predicts a violation of energy conservation almost certainly is in error. This is a non-controversial and fundamental fact regarding the mathematical structure of the theories, regardless of whether the theories themselves are or are not correct descriptions of the physical world. Accordingly, the results reported regarding the EmDrive, if true, would demonstrate that existing physical theory (or its application in engineering) is incorrect or incomplete.
The EmDrive has been compared to the previous Dean Drive, in that an oscillatory motion is set up so that it has a different effect in each direction of the stroke, in the hope that momentum transfer will differ in each direction, except in this case the oscillations are said to be electromagnetic.
Conservation of momentum is also required and maintained in Maxwell's equations, Newtonian mechanics, Special relativity and quantum mechanics (and their combination, quantum electrodynamics), so this claim cannot be valid unless these well-established physical theories are false or can be otherwise explained in terms within these existing theories.
Shawyer's calculations may be in error. He may have incorrectly identified the forces on the sides of the waveguide. If an error is present, it is most likely that the 'thrust' is eliminated and the drive then cannot accelerate. Despite some criticism Shawyer still claims his machines work.
Any dispute will be settled when independent observations are able to conclude whether or not the machine works in the way it is claimed. | EmDrive
EmDrive (also Relativity Drive) is the name of a spacecraft propulsion system proposed, and reportedly developed, by Roger Shawyer.[1] New Scientist ran a cover story on EmDrive in its September 8, 2006 issue.[1] The device is a Magnetron with a specially shaped fully enclosed tapering resonator cavity whose area is greater at one end. The inventor claims that the device generates thrust even though no detectable energy leaves the device. The inventor proposes to use it as a spacecraft propulsion system that uses no fuel (other than electricity).
On his homepage[1] the inventor claims that independent peer-review is underway, but so far no publication is available.
The device's operation as described seemingly violates several basic laws of physics, notably conservation of momentum, though the inventor insists to the contrary. John Costella, an expert in relativistic electrodynamics describes the EmDrive as a 'fraud'.
# Principle of operation
The device exploits an idea first suggested by Allen Cullen in the 1950's, an electrical engineer then at University College London, that involves forces created by reflecting microwaves between opposite walls of a cavity. The "idea" is to try to design a cavity in such a manner that forces on one side are greater than the other.
The drive comprises a resonant cavity flooded with microwave radiation. The radiation exerts radiation pressure on the walls of the cavity, and normal Newtonian mechanics would indicate that, no matter what shape the cavity is, the forces exerted upon it from within must balance to zero. Shawyer claims that relativistic effects cause a cavity shaped like a truncated cone to experience a larger force against the large end than the small end, due to the group velocity of the wave changing as the local diameter of the cavity varies.
The increased confinement of the tapered end of the cone leads to a higher effective propagation constant (phase velocity). It also leads to local reflections which account for the apparent force imbalance when considering only the end walls. However, since it is the phase of the light rather than the actual photons bouncing off the walls, each force acts quasi independently from another - much like in a ring laser gyroscope where the beams act as if having an external frame of reference (which they have, since the speed of light is constant). The same principle applies to the EmDrive.
No microwaves or anything else are allowed to leave the device. Since nothing leaves the drive for propulsive purposes an EmDrive can be classed as a reactionless drive. Thus the principle by which the EmDrive is supposed to operate seems to violate conservation of momentum. It is known that the physics equations describing microwaves, Maxwell's equations, conserve momentum, and this would seem to cast doubt on Shawyer's derivation of a thrust effect. In his paper (attached), Shawyer thus takes the following view: any thrust extracted from his device is directly withdrawn from the energy stored in his cavity (due to the Q reflections an average wave encounters when inserted into the cavity, the energy levels quickly build up). In other words: the apparent force on the wider diameter of the cone seems to wane. The extent to which that happens perfectly matches the amount predicted by the law of conservation of momentum.
# Criticism
The EmDrive was the cover story for the September 8, 2006 issue of New Scientist.[1]
After receiving criticism that no peer-reviewed publications on the subject had been made, Mr. Shawyer submitted a theory paper to New Scientist (which is not a peer reviewed scientific journal) [2] Shawyer's paper was almost immediately challenged[3] by Dr. John Costella, a theoretical physicist and electrical engineer who works for the Australian Department of Defence, whose Ph.D. is in relativistic electrodynamics, the field of physics that Mr. Shawyer relies on to support his theory.
# Prototypes and tests
In September 2006 it was reported[1] that Shawyer had constructed a prototype unit weighing 9 kilogrammes that consumes 700 watts of power and produces 88 millinewtons of force.
In May 2007 Eureka magazine reported that a second unit has been built for demonstration purposes, weighing 100 kilogrammes, consuming 300 watts for microwave production (and an unspecified amount for ancillary purposes such as cooling) and producing 9.8 grams (96.1 millinewtons) of force during testing in October 2006. Unlike the prototype unit, which can only be run for short periods before burning out its magnetron, the demonstration unit can be run continuously. [4]
The limiting factor for performance is claimed to be the Q factor of the cavity, as microwave energy lost to heating the cavity reduces the field strength within, so Shawyer is experimenting with a cavity lined in a superconducting material that may produce Q factors sufficient to build a device capable of generating 30 newtons per watt.
These results have neither been reproduced by other scientists or engineers, nor have they been published in a peer-reviewed scientific journal.
# New Scientist article
EmDrive was featured on the cover of issue 2568 of New Scientist, a weekly science magazine. The article portrayed the device as plausible, and emphasized the arguments of those who held that point of view, although it did quote one engineer as saying "it's a load of bloody rubbish." The article included the following arguments from proponents of the theory:
- With a grant from the UK government's Department of Trade and Industry of £250,000, (actually two grants; one a feasibility study of £45,000 and a second of £81,000 to build a demonstration engine - source SPR Ltd.) a commercial regulatory and support agency,[5] Shawyer has built two prototypes that reportedly produce 16mN and 300mN of thrust respectively; each using 1kW of electrical power. A condition of the funding was independent analysis, which was recently completed by John Spiller who says "The thruster's design is practical and could be adapted fairly easily to work in outer space". Shawyer claims that he has been visited by representatives from China and the US Air Force, but ESA has not yet shown much interest. He estimates that his design could save the aerospace community $15 billion over the next ten years.
- Engineers in Germany have created superconducting resonators (for use in particle accelerators) with Q values of several billion, which Shawyer claims would equate to a thrust of 30kN per kilowatt, "enough to lift a large car". Shawyer states that the thruster works best while stationary relative to their thrust.
New Scientist has drawn great criticism from the scientific community due to the uncritical treatment of EmDrive in its article. Science fiction writer Greg Egan distributed a public letter stating that "a sensationalist bent and a lack of basic knowledge by its writers" was making the magazine's coverage sufficiently unreliable "to constitute a real threat to the public understanding of science". In particular, Egan found himself "gobsmacked by the level of scientific illiteracy" in the magazine's coverage of the EmDrive, where New Scientist allowed the publication of "meaningless double-talk" designed to bypass a fatal objection to Sawyer's proposed space drive, namely that it violates the conservation of momentum. Egan urged those reading his letter to write to New Scientist and pressure the magazine to raise its standards, instead of "squandering the opportunity that the magazine's circulation and prestige provides" for genuine science education. The letter was endorsed by mathematical physicist John C. Baez and posted on his blog.[6]
Egan has also recommended[6] that New Scientist publish Costella's refutation[3] of Shawyer's theory paper[2].
# Analysis
Any claim of a reactionless drive is treated with skepticism by the physics community, since it violates well-established principles such as the conservation of momentum and conservation of energy, both of which have enormous experimental support.
Since there are no known phenomena that do not conserve energy, any calculation based on standard physical theory that predicts a violation of energy conservation almost certainly is in error. This is a non-controversial and fundamental fact regarding the mathematical structure of the theories, regardless of whether the theories themselves are or are not correct descriptions of the physical world. Accordingly, the results reported regarding the EmDrive, if true, would demonstrate that existing physical theory (or its application in engineering) is incorrect or incomplete.[citation needed]
The EmDrive has been compared to the previous Dean Drive, in that an oscillatory motion is set up so that it has a different effect in each direction of the stroke, in the hope that momentum transfer will differ in each direction, except in this case the oscillations are said to be electromagnetic.
Conservation of momentum is also required and maintained in Maxwell's equations, Newtonian mechanics, Special relativity and quantum mechanics (and their combination, quantum electrodynamics), so this claim cannot be valid unless these well-established physical theories are false or can be otherwise explained in terms within these existing theories.
Shawyer's calculations[2] may be in error.[3] He may have incorrectly identified the forces on the sides of the waveguide. If an error is present, it is most likely that the 'thrust' is eliminated and the drive then cannot accelerate. Despite some criticism Shawyer still claims his machines work.
Any dispute will be settled when independent observations are able to conclude whether or not the machine works in the way it is claimed. | https://www.wikidoc.org/index.php/EmDrive | |
3f5d3995633feb2163df6e6a5a626eafc4a2673c | wikidoc | Emetine | Emetine
# Overview
Emetine is a drug used as both an anti-protozoal and to induce vomiting. It is produced from the ipecac root.
# Early emetine-based preparations
Early use of emetine was in the form of oral administration of the extract of ipecac root, or ipecacuhana. This extract was originally thought to contain only one alkaloid, emetine, but was found to contain several, including cephaeline, emetine, psychotrine and others. Although this therapy was reportedly successful, the extract caused vomiting in many patients which reduced its utility. In some cases, it was given with opioids to reduce nausea. Other suggestions to reduce nausea involved coating the drug to allow it to be released after digestion in the stomach.
# Use of emetine as anti-amoebic
The identification of emetine as a more potent agent improved the treatment of amoebiasis. While use of emetine still caused nausea, it was more effective than the crude extract of ipecac root. Additionally, emetine could be administered hypodermically which still produced nausea, but not to the degree experienced in oral administration.
Although it is a potent anti-protozoal, the drug also can interfere with muscle contractions, leading to cardiac failure in some cases. Because of this, in some uses it is required to be administered in a hospital environment so that adverse events can be addressed.
# Development of dehydroemetine
Dehydroemetine is a synthetically produced drug similar to emetine in its anti-amoebic properties, but it produces fewer side effects. In the United States, it is manufactured by Roche and distributed by the Center for Disease Control on a compassionate use basis as an investigational drug for the treatment of metronidazole-resistant amoebiasis.
Some examples of the use of dehydroemetine in the treatment of amoebic infections include:
- In 1993, the successful treatment of cutaneous amoebiasis in a 7-year old girl with dehydroemetine and metronidazole in Mexico.
- A double-blind study of oral dehydroemetine in the treatment of amoebiasis performed at St. Mary's Hospital, Catholic Medical College, Seoul, Republic of Korea in 1973-1974 showed that dehydroemetine treatment was effective. A total of 60 patients were treated, 20 with dehydroemetine, 20 with Tiberal, and 20 with metronidazole. 25% of patients treated with dehydroemetine reported adverse reactions, compared to 20% with other drugs, but no patient discontinued therapy due to the reaction. In all three cases, the drug therapy resulted in clearance of the infection, defined as negative results through an O&P exam, in all but 1-2 patients.
- A 1979 study of 27 patients treated with dehydroemetine and various other drugs suggested that all drug combinations were successful at treating amoebic liver abscesses.
- A 1986 in-vitro study compared the effects of dehydroemetine, metronidazole, ornidazole, and secnidazole on Entamoeba histolytica. Metronidazole was found to be most effective, and the other three drugs were of similar effectiveness.
# Dehydroemetine therapy in other diseases
A 1980 report described the use of dehydroemetine in treatment of herpes zoster, a condition which can produce painful neurological symptoms. The study involved 40 patients, all of whom were over 60, and compared dehydroemetine treatment to another drug. The study reported patients treated with dehydroemetine experienced relief of neuralgia with no changes in cardiovascular functions.
Dehydroemetine has been investigated as a treatment for Leishmania infection. | Emetine
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Emetine is a drug used as both an anti-protozoal and to induce vomiting. It is produced from the ipecac root.
# Early emetine-based preparations
Early use of emetine was in the form of oral administration of the extract of ipecac root, or ipecacuhana. This extract was originally thought to contain only one alkaloid, emetine, but was found to contain several, including cephaeline, emetine, psychotrine and others. Although this therapy was reportedly successful, the extract caused vomiting in many patients which reduced its utility. In some cases, it was given with opioids to reduce nausea. Other suggestions to reduce nausea involved coating the drug to allow it to be released after digestion in the stomach.
[1]
# Use of emetine as anti-amoebic
The identification of emetine as a more potent agent improved the treatment of amoebiasis. While use of emetine still caused nausea, it was more effective than the crude extract of ipecac root. Additionally, emetine could be administered hypodermically which still produced nausea, but not to the degree experienced in oral administration.
Although it is a potent anti-protozoal, the drug also can interfere with muscle contractions, leading to cardiac failure in some cases. Because of this, in some uses it is required to be administered in a hospital environment so that adverse events can be addressed.
# Development of dehydroemetine
Dehydroemetine is a synthetically produced drug similar to emetine in its anti-amoebic properties, but it produces fewer side effects. In the United States, it is manufactured by Roche and distributed by the Center for Disease Control on a compassionate use basis as an investigational drug for the treatment of metronidazole-resistant amoebiasis. [2]
Some examples of the use of dehydroemetine in the treatment of amoebic infections include:
- In 1993, the successful treatment of cutaneous amoebiasis in a 7-year old girl with dehydroemetine and metronidazole in Mexico. [3]
- A double-blind study of oral dehydroemetine in the treatment of amoebiasis performed at St. Mary's Hospital, Catholic Medical College, Seoul, Republic of Korea in 1973-1974 showed that dehydroemetine treatment was effective. A total of 60 patients were treated, 20 with dehydroemetine, 20 with Tiberal, and 20 with metronidazole. 25% of patients treated with dehydroemetine reported adverse reactions, compared to 20% with other drugs, but no patient discontinued therapy due to the reaction. In all three cases, the drug therapy resulted in clearance of the infection, defined as negative results through an O&P exam, in all but 1-2 patients.[4]
- A 1979 study of 27 patients treated with dehydroemetine and various other drugs suggested that all drug combinations were successful at treating amoebic liver abscesses. [4]
- A 1986 in-vitro study compared the effects of dehydroemetine, metronidazole, ornidazole, and secnidazole on Entamoeba histolytica. Metronidazole was found to be most effective, and the other three drugs were of similar effectiveness. [5]
# Dehydroemetine therapy in other diseases
A 1980 report described the use of dehydroemetine in treatment of herpes zoster, a condition which can produce painful neurological symptoms. The study involved 40 patients, all of whom were over 60, and compared dehydroemetine treatment to another drug. The study reported patients treated with dehydroemetine experienced relief of neuralgia with no changes in cardiovascular functions. [6]
Dehydroemetine has been investigated as a treatment for Leishmania infection. [7] | https://www.wikidoc.org/index.php/Emetine | |
ebe5a2849d2d2dd505ad206f7ca3a87b56102a39 | wikidoc | Emetrol | Emetrol
Emetrol is the brand name of an over-the-counter antiemetic medicine taken to relieve nausea and vomiting. It is a mixture of glucose, fructose, and phosphoric acid, and comes in syrup form.
Each dose (5mL) contains 1.87g of glucose, 1.87g of fructose and 21.5mg of phosphoric acid. The inactive ingredients are FD&C red No. 40, flavors, glycerin, methylparaben, and purified water.
Since Emetrol contains fructose it should not be taken by anyone with hereditary fructose intolerance (HFI). Diabetics should speak with a doctor before taking this medication.
Reference: Pfizer-Emetrol
It should not be taken for more than one hour (5 doses) without consulting a physician. If upset stomach continues or recurs frequently, consult a physician.
For maximum effectiveness, never dilute the medicine or drink fluids of any kind immediately before or after taking. | Emetrol
Emetrol is the brand name of an over-the-counter antiemetic medicine taken to relieve nausea and vomiting. It is a mixture of glucose, fructose, and phosphoric acid, and comes in syrup form.
Each dose (5mL) contains 1.87g of glucose, 1.87g of fructose and 21.5mg of phosphoric acid. The inactive ingredients are FD&C red No. 40, flavors, glycerin, methylparaben, and purified water.
Since Emetrol contains fructose it should not be taken by anyone with hereditary fructose intolerance (HFI). Diabetics should speak with a doctor before taking this medication.
Reference: Pfizer-Emetrol
It should not be taken for more than one hour (5 doses) without consulting a physician. If upset stomach continues or recurs frequently, consult a physician.
For maximum effectiveness, never dilute the medicine or drink fluids of any kind immediately before or after taking.
Template:Pharma-stub
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Emetrol | |
d1f24be510a1a02cf4508d1ea3494f1db83d09db | wikidoc | Emotion | Emotion
# Overview
An emotion is a "complex reaction pattern, involving experiential, behavioral, and physiological elements, by which the individual attempts to deal with a personally significant matter of event." It arises without conscious effort and is either positive or negative in its valence.
Other closely related terms are:
- affect, a synonym for emotion
- affect display, external display of emotion
- disposition, referring to a durable differentiating characteristic of a person, a tendency to react to situations with a certain emotion
- feeling, which usually refers to the subjective, phenomenological aspect of emotion
- mood, which refers to an emotional state of duration intermediate between an emotion and a disposition
# Etymology
Emotion is derived from French émotion, from émouvoir, 'excite' based on Latin emovere, from e- (variant of ex-) 'out' and movere 'move'. "Motivation" is also derived from movere.
# Definitions of emotion
Emotion is very complex, and the term has no single universally accepted definition. The study of emotions is part of psychology, neuroscience, and ethics.
According to Sloman, emotions are cognitive processes. Some authors emphasize the difference between human emotions and the affective behavior of animals.
We often talk about brains as information-processing systems, but any account of the brain that lacks an account of emotions, motivations, fears, and hopes is incomplete. Emotions are measurable physical responses to salient stimuli: the increased heartbeat and perspiration that accompany fear, the freezing response of a rat in the presence of a cat, or the extra muscle tension that accompanies anger. Feelings, on the other hand, are the subjective experiences that sometimes accompany these processes: the sensations of happiness, envy, sadness, and so on. Emotions seem to employ largely unconscious machinery—for example, brain areas involved in emotion will respond to angry faces that are briefly presented and then rapidly masked, even when subjects are unaware of having seen the face. Across cultures the expression of basic emotions is remarkably similar, and as Darwin observed, it is also similar across all mammals. There are even strong similarities in physiological responses among humans, reptiles, and birds when showing fear, anger, or parental love.
Modern views propose that emotions are brain states that quickly assign value or valence to outcomes and provide a simple plan of action. Thus, emotion can be viewed as a type of computation, a rapid, automatic summary that initiates appropriate actions. When a bear is galloping toward you, the rising fear directs your brain to do the right things (determining an escape route) instead of all the other things it could be doing (rounding out your grocery list). When it comes to perception, you can spot an object more quickly if it is, say, a spider rather than a roll of tape. In the realm of memory, emotional events are laid down differently by a parallel memory system involving a brain area called the amygdala.
One goal of emotional neuroscience is to understand the nature of the many disorders of emotion, depression being the most common and costly. Impulsive aggression and violence are also thought to be consequences of faulty emotion regulation.
# The function of emotion (relations between: Emotion, Meta-emotion, and Reason)
Emotion is generally regarded by Western civilization as the antithesis of reason. This distinction stems from Western philosophy specifically Cartesian dualism and modern interpretations of Stoicism, and is reflected in common phrases like appeal to emotion or your emotions have taken over.
In Paul D. MacLean's Triune brain model, emotions are defined as the responses of the Mammalian cortex. Emotion competes with even more instinctive responses from the Reptilian cortex and the more logical, reasoning neocortex. However, current research on the neural circuitry of emotion suggests that emotion is an essential part of human decision-making and planning, and that the famous distinction made by Descartes between reason and emotion is not as clear as it seems.
Emotions can be undesired either to the individual experiencing them, but also can be undesired to the other persons, groups of persons, organizations, sub-cultures, and civilizations such as Western civilization, which can be viewed as the emotion being subjected to the individual's or someone else's discouraging meta-emotion about the undesired emotion or can be even repressed by the meta-emotions. Thus one of the most distinctive, and perhaps challenging, facts about human beings is this potential for entanglement, or possibly opposition, between emotion, meta-emotion, will, and reason.
Some state that there is no empirical support for any generalization suggesting the antithesis between reason and emotion: indeed, anger or fear can often be thought of as a systematic response to observed facts. In any case, it is clear that the relation between logic and argument and emotion is one which merits careful study.
Emotion as the subject of scientific research has multiple dimensions: behavioral, physiological, subjective, and cognitive. Sloman argues that many emotions are side-effects of the operations of complex mechanisms (e.g. 'alarm' mechanisms) required in animals or machines with multiple motives and limited capacities and resources for coping with a changing and unpredictable world, just as 'thrashing' can sometimes occur as a side-effect of scheduling and memory management mechanisms required in a computer operating system for purposes other than producing thrashing. Such side effects are sometimes useful, but sometimes they are dysfunctional. Other theorists, often influenced by writings of Antonio Damasio argue that emotions themselves are necessary for any intelligent system (natural or artificial).
Psychiatrist William Glasser's theory of the human control system states that behavior is composed of four simultaneous components: deeds, ideas, emotions, and physiological states. He asserts that we choose the idea and deed and that the associated emotions and physiological states also occur but cannot be chosen independently. He calls his construct a total behavior to distinguish it from the common concept of behavior. He uses the verbs to describe what is commonly seen as emotion. For example, he uses 'to depress' to describe the total behavior commonly known as depression which, to him, includes depressing ideas, actions, emotions, and physiological states. Dr. Glasser also further asserts that internal choices (conscious or unconscious) cause emotions instead of external stimuli.
According to Damasio, feeling can be viewed as the subjective experience of an emotion that arises physiologically in the brain.
Many psychologists adopt the ABC model, which defines emotions in terms of three fundamental attributes: A. physiological arousal, B. behavioral expression (e.g. facial expressions), and C. conscious experience, the subjective feeling of an emotion. All three attributes are necessary for a full fledged emotional event, though the intensity of each may vary greatly.
Robert Masters makes the following distinctions between affect, feeling and emotion: "As I define them, affect is an innately structured, non-cognitive evaluative sensation that may or may not register in consciousness; feeling is affect made conscious, possessing an evaluative capacity that is not only physiologically based, but that is often also psychologically (and sometimes relationally) oriented; and emotion is psychosocially constructed, dramatized feeling."
In pop culture there are sub-cultures which cultivate the expressions of anger and rebelliousness even when they are not really angry, its members encouraging each other to express the anger by internalizing meta-gladness about it.
Encouragement (i.e. meta-gladness) and discouragement (i.e. psychological repression) of selected emotions - instead of mere awareness and equal interest in all emotions - can be considered as additional source of organizational climate, family dynamics, psychodynamics, personality traits, and of mental disorders, including depression among others.
## Emotions in the Philosophy of Mind
In opposition to the traditional Philosophy of Mind that has considered emotions only as non-essential addition, at best giving a flavour to rational intellectual thought, the authors of naturalistic Philosophy of Mind inspired by prospects of building robots and other autonomous agents are starting to give emotions a central role as an indispensable constituent for adaptive agency (see DeLancey 2002/2004).
## Emotions in Decision Making
There is increasing support for treating people's emotions as an information source in their decision making process.
## Emotions in Philosophy
What is the relationship between reason and emotion?
4 Maccabees echoes nearly the same idea, and "philosophically" discusses the reason versus emotion in an argument that if reason rules the emotions that prevent self-control, then it may rule the emotions that stop people from acting justly (malice) and courageously (anger, fear and pain), and describes primary emotions using a branching and farming analogy. In short:
Such basic views of emotions have seen the world through thousands of years, leading to ideas like the age of reason, age of enlightenment (ironically scorned by many Christians) and logical positivism, and affecting the history of logic, reason and science from its roots to its latest stems.
Conversely, emotional people experience reason as cold, irrational and evil, despite its benefits. There is no use to proving wrong such meaningless, logic-eschewing beliefs that don't want to or claim to be reasonable.
# Theoretical traditions in Psychogical Emotion Research
Several theoretical traditions in emotion research have been offered. These traditions are not mutually exclusive and many researchers incorporate multiple perspectives in their work.
## Somatic theories
William James in the late 19th century believed that emotional experience is largely due to the experience of bodily changes. These changes might be visceral, postural, or facially expressive. The most basic of these somatic theories is the James-Lange theory. This theory and its derivates state that a changed situation leads to a changed bodily state. It is this bodily state which in turn gives rise to an emotion. Hence the emotion fear upon encountering a bear in the woods would follow from:
This approach underlies experiment where through manipulating the bodily state, a desired emotion is induced (e.g. in laughter therapy).
## The Cannon-Bard theory
Walter Cannon provided empirical evidence against the dominance of the James-Lange theory of the physiological aspects emotions in the second edition of Bodily Changes in Pain, Hunger, Fear and Rage. Cannon and Bard came up with a different account of the relations between emotions and behavior; where a certain situation leads to an emotion; which in turn activates a typical behavior. Here the emotion fear upon encountering a bear in the woods would result in:
## Cognitive theories
Research in social psychology interprets emotions as a combination of two elements; physiological arousal and cognitive interpretation. The earliest account of such a theory is the Singer-Schachter theory that is based on experiments that varied arousal introducing chemical (adrenaline) and put the participants in different situations. The combination of the appraisal of the situation (cognitive) and whether participants received adrenaline or a placebo together determined the response. In the example of the bear this would lead to:
Several other theories have a similar ideas, for example, the framework proposed by Nico Frijda where such appraisal leads to action tendencies is related to this idea.
In all these theories, the different emotions causes a detectable physical response in the body. These responses are often perceived as sensation in the body; for example:
- Fear is felt as a heightened heartbeat, increased “flinch” response, and increased muscle tension.
- Anger, based on sensation, seems indistinguishable from fear.
- Happiness is often felt as an expansive or swelling feeling in the chest and the sensation of lightness or buoyancy, as if standing underwater.
- Sadness is often experienced as a feeling of tightness in the throat and eyes, and relaxation in the arms and legs.
- Shame can be felt as heat in the upper chest and face.
- Desire can be accompanied by a dry throat, heavy breathing, and increased heart rate.
## The evolutionary perspective
A fourth theoretical tradition has been gaining influence once more (see: Cornelius, 1996).
This fourth, evolutionary tradition, started in the late 19th century with Charles Darwin's publication of a book on the expression of emotions in man and animals. Darwin's original thesis was that emotions evolved via natural selection for reasons of warning other creatures about your intentions (e.g. a cat with a high back is angry and will strike you unless you back off). Darwin argued that for mankind emotions were no longer functional but are epiphenomena of functional associated habits. Such an evolutionary origin would predict emotions to be cross-culturally universal. Confirmation of this biological origin was provided by Paul Ekman's seminal research on facial expressions in humans. Other research in this area focuses on physical displays of emotion including body language of animals and facial expressions in humans. (See Affect display.) The increased potential in neuroimaging has allowed investigation of this idea focusing on the working brain itself. Important neurological advances where made from this perspectives in the 1990s by, for example, Joseph LeDoux and Antonio Damasio.
### Primary and secondary emotion
Primary emotions (i.e., innate emotions, such as fear) "depend on limbic system circuitry," with the amygdala and anterior cingulate gyrus being "key players".
- Smell carries directly to limbic areas of the mammalian brain via nerves running from the olfactory bulbs to the septum, amygdala, and hippocampus. In the acquatic brain, olfaction was critical for detecting food, foes, and mates from a distance in murky waters.
- An emotional feeling, like an aroma, has a volatile or "thin-skinned" quality because sensory cells lie on the exposed exterior of the olfactory epithelium (i.e., on the bodily surface itself).
- A sudden scent, like a whiff of smelling salts, may jolt the mind. The force of a mood is reminiscent of a smell's intensity (e.g., soft and gentle, pungent, or overpowering), and similarly permeates and fades as well. The design of emotion cues, in tandem with the forebrain's olfactory prehistory, suggests that the sense of smell is the neurological model for our emotions.
Secondary emotions (i.e., feelings attached to objects , events, and situations through learning) require additional input, based largely on memory, from the prefrontal and somatosensory cortices. The stimulus may still be processed directly via the amygdala but is now also analyzed in the thought process. Thoughts and emotions are interwoven: every thought, however bland, almost always carries with it some emotional undertone, however subtle.
## Neurobiological theories of emotion
Based on discoveries made through neural mapping of the limbic system, the neurobiological explanation of human emotion is that emotion is a pleasant or unpleasant mental state organized in the limbic system of the mammalian brain.
Defined as such, these emotional states are specific manifestations of non-verbally expressed feelings of agreement, amusement, anger, certainty, control, disagreement, disgust, disliking, embarrassment, fear, guilt, happiness, hate, interest, liking, love, sadness, shame, surprise, and uncertainty. If distinguished from reactive responses of reptiles, emotions would then be mammalian elaborations of general vertebrate arousal patterns, in which neurochemicals (e.g., dopamine, noradrenaline, and serotonin) step-up or step-down the brain's activity level, as visible in body movements, gestures, and postures. In mammals, primates, and human beings, feelings are displayed as emotion cues.
For example, the human emotion of love is proposed to have evolved from paleocircuits of the mammalian brain (specifically, modules of the cingulated gyrus) designed for the care, feeding, and grooming of offspring. Paleocircuits are neural platforms for bodily expression configured millions of years before the advent of cortical circuits for speech. They consist of pre-configured pathways or networks of nerve cells in the forebrain, brain stem and spinal cord. They evolved prior to the earliest mammalian ancestors, as far back as the jawless fishes, to control motor function.
Presumably, before the mammalian brain, life in the non-verbal world was automatic, preconscious, and predictable. The motor centers of reptiles react to sensory cues of vision, sound, touch, chemical, gravity, and motion with pre-set body movements and programmed postures. With the arrival of night-active mammals, circa 180 million years ago, smell replaced vision as the dominant sense, and a different way of responding arose from the olfactory sense, which is proposed to have developed into mammalian emotion and emotional memory. In the Jurassic Period, the mammalian brain invested heavily in olfaction to succeed at night as reptiles slept — one explanation for why olfactory lobes in mammalian brains are proportionally larger than in the reptiles. These odor pathways gradually formed the neural blueprint for what was later to become our limbic brain.
### Brain areas related to emotion
Emotions are thought to be related to activity in brain areas that direct our attention, motivate our behavior, and determine the significance of what is going on around us. Pioneering work by Broca (1878), Papez (1937), and MacLean (1952) suggested that emotion is related to a group of structures in the center of the brain called the limbic system, which includes the hypothalamus, cingulate cortex, hippocampi, and other structures. More recent research has shown that some of these limbic structures are not as directly related to emotion as others are, while some non-limbic structures have been found to be of greater emotional relevance. The following brain structures are currently thought to be most involved in emotion:
- Amygdala — The amygdalae are two small, round structures located anterior to the hippocampi near the temporal poles. The amygdalae are involved in detecting and learning what parts of our surroundings are important and have emotional significance. They are critical for the production of emotion, and may be particularly so for negative emotions, especially fear.
- Prefrontal cortex — The term prefrontal cortex refers to the very front of the brain, behind the forehead and above the eyes. It appears to play a critical role in the regulation of emotion and behavior by anticipating the consequences of our actions. The prefrontal cortex may play an important role in delayed gratification by maintaining emotions over time and organizing behavior toward specific goals.
- Anterior cingulate — The anterior cingulate cortex (ACC) is located in the middle of the brain, just behind the prefrontal cortex. The ACC is thought to play a central role in attention, and may be particularly important with regard to conscious, subjective emotional awareness. This region of the brain may also play an important role in the initiation of motivated behavior.
- Ventral striatum — The ventral striatum is a group of subcortical structures thought to play an important role in emotion and behavior. One part of the ventral striatum called the nucleus accumbens is thought to be involved in the experience of goal-directed positive emotion. Individuals with addictions experience increased activity in this area when they encounter the object of their addiction.
- Insula — The insular cortex is thought to play a critical role in the bodily experience of emotion, as it is connected to other brain structures that regulate the body’s autonomic functions (heart rate, breathing, digestion, etc.). This region also processes taste information and is thought to play an important role in experiencing the emotion of disgust.
### Positive and negative perception
Like aromas, emotions are experienced as either positive or negative, pleasant or unpleasant; emotions do not seem to be neutral. Like odors, feelings come and go, but are logical, and clearly show upon our face in mood signs. It is likely that many emotions evolved from aroma paleocircuits a. in subcortical nuclei (e.g., the paleocortex of the amygdala), and b. in layers of nerve cells within the forebrain's outer covering of neocortex. The latter's stratified architecture resembles that of the olfactory bulb, which is organized in layers as well.
# Sociology of Emotions
Systematic observations of group interaction found that a substantial portion of group activity is devoted to the socio-emotional issues of expressing affect and dealing with tension. Simultaneously, field studies of social attraction in groups revealed that feelings of individuals about each other collate into social networks, a discovery that still is being explored in the field of social network analysis.
Ethnomethodology revealed emotional commitments to everyday norms through purposeful breaching of the norms. For example, students acting as boarders in their own homes reported others' astonishment, bewilderment, shock, anxiety, embarrassment, and anger; family members accused the students of being mean, inconsiderate, selfish, nasty, or impolite. Actors who breach a norm themselves feel waves of emotion, including apprehension, panic, and despair. However, habitual rule breaking leads to declining stress, and may eventually end in enjoyment.
T. David Kemper proposed that people in social interaction have positions on two relational dimensions: status and power. Emotions emerge as interpersonal events change or maintain individuals' status and power. For example, affirming someone else's exalted status produces love-related emotions. Increases or decreases in one's own and other's status or power generate specific emotions whose quality depends on the patterns of change.
Sociologist Randall Collins has stated that emotional energy is the main motivating force in social life, for love and hatred, investing, working or consuming, rendering cult or waging war. Emotional energy ranges from the highest heights of enthusiasm, self-confidence and initiative to the deepest depths of apathy, depression and retreat. Emotional energy comes from variously successful or failed chains of interaction rituals, that is, patterned social encounters –from conversation or sexual flirtation through Christmas family dinners or office work to mass demonstrations, organizations or revolutions. In the latter, the coupling of participants' behavior synchronizes their nervous systems to the point of generating a collective effervescence, one observable in their mutual focus and emotional entraining, as well as in their loading of emotional and symbolic meaning to entities which subsequently become emblems of the ritual and of the membership group endorsing, preserving, promoting and defending them. Thus social life would be most importantly about generating and distributing emotional energy.
Thomas J. Scheff established that many cases of social conflict are based on a destructive and often escalating, but stoppable and reversible shame-rage cycle: when someone results or feels shamed by another, their social bond comes under stress. This can be cooperatively acknowledged, talked about and – most effectively when possible - laughed at so their social bond may be restored. Yet, when shame is not acknowledged, but instead negated and repressed, it becomes rage, and rage may drive to aggressive and shaming actions that feed-back negatively on this self-destructive situation. The social management of emotions might be the fundamental dynamics of social cooperation and conflict around resources, complexity, conflict and moral life. It is well-established sociological fact that expression and feeling of the emotion of anger, for example, is strongly discouraged (repressed) in girls and women in many cultures, while fear is discouraged in boys and men. Some cultures and sub-cultures encourage or discourage happiness, sadness, jealousy, excitedness, and many other emotions. The free expression of the emotion of disgust is considered socially unacceptable in many countries.
Arlie Hochschild proposed that individuals apply cultural and ideological standards to judge the suitability of emotions occurring during a social interaction, and then manage their feelings to produce acceptable displays. Hochschild showed that jobs often require such emotional labor. Her classic study of emotional labor among flight attendants found that an industry speed-up, reducing contact between flight attendants and passengers, made it impossible for flight attendants to deliver authentic emotional labor, so they ended up surface-acting superficial smiles. Peggy Thoits divided emotion management techniques into implementation of new events and reinterpretation of past events. Thoits noted that emotions also can be managed with drugs, by performing faux gestures and facial expressions, or by cognitive reclassifications of one's feelings.
Affect Control Theory which was originated by David R. Heise proposes that social actions are designed by their agents to create impressions that befit sentiments reigning in a situation. Emotions are transient personal states depending on the current impression of the emoting person, and on the comparison of that impression with the sentiment attached to the person's identity.
# Classification of emotions
There has been considerable debate whether emotions should be classified as a position in a continuum (e.g. the circumplex model by Russell, or many of the valence approaches in social psychology) or whether emotions are best identified as distinct (basic) states.
## Classification by basic emotions
One of the most influential classification approaches in the study of emotion is Robert Plutchik’s classification into eight primary emotions. The emotions that Plutchik lists as primary are:
- anger
- fear
- sadness
- joy
- disgust
- curiosity/interest
- surprise
- acceptance
Similar to the way primary colors combine, primary emotions are believed to blend together to form the full spectrum of human emotional experience. Plutchik reasons that these eight are primary on evolutionary grounds, by relating each to behavior with survival value. For example: fear motivates flight from danger, anger motivates fighting for survival. They are considered to be part of our biological heritage and built into human nature.
Paul Ekman devised a similar list of basic emotions from cross-cultural research on the Fore tribesmen of Papua New Guinea. He found that even members of an isolated, stone age culture could reliably identify the expressions of emotion in photographs of people from cultures which the Fore were not yet familiar, and concluded that the facial expression of some basic emotions is innate. The following is Ekman’s list of basic emotions:
- anger
- fear
- sadness
- happiness
- disgust
Ekman holds that this lends further support to the view that at least some emotions are primary, innate, and universal in all human beings.
Lazarus (1991) similarly offers a taxonomy of 'Core Relational Themes' for various emotions; these help define both function and eliciting conditions. They include a demeaning offense against me and mine for anger; facing an immediate, concrete, and overwhelming physical danger for fear; having experienced an irrevocable loss for sadness; taking in or being too close to an indigestible object or idea (metaphorically speaking) for disgust; making reasonable progress toward the realization of a goal for happiness.
# Emotions and Psychotherapy
Depending on the particular school's general emphasize either on cognitive component of emotion, physical energy discharging, or on symbolic movement and facial expression components of emotion, different schools of psychotherapy approach human emotions differently. While, for example, the school of Re-evaluation Counseling propose that distressing emotions are to be relieved by “discharging” them - hence crying, laughing, sweating, shaking, and trembling. other more cognitively oriented schools approach them via their cognitive components, or via symbolic movement and facial expression components (like in contemporary Gestalt therapy).
# Meta-emotions
Meta-emotion refers in accordance with the general definition of the prefix "meta-" to second-order emotions about first-order emotions. Meta-emotions can be short-lived or long-lived. The latter can be a source of discouragement or even psychological repression, or encouragement of specific emotions, having implications for personality traits, psychodynamics, organizational climate, emotional disorders, but also emotional awareness, and emotional intelligence.
# Emotions and computer models, artificial intelligence and computing
A flurry of recent work in computer science, engineering, psychology and neuroscience is aimed at developing devices that recognize human affect display and modelling emotions generally (Fellous, Armony & LeDoux, 2002).
# Emotion in animals
Animals have physiological responses that are analogous to human emotional responses, as has been recognized at least since Darwin published The Expression of Emotions in Man and Animals in 1872.
# Notes
- ↑ vandenBos, Gary B. (2006). APA Dictionary of Psychology. Washington, DC: American Psychological Association
- ↑ Emotional Competency discussion of emotion
- ↑ Sloman, Aaron (1981) Why Robots Will Have Emotions. In proc.. University of Sussex, UK
- ↑ Damasio, Antonio (1994) Descartes Error Penguin Putnam, New York, New York
- ↑ Damasio, Antonio (1994) Descartes Error Penguin Putnam, New York, New York
- ↑ Masters, Robert (2000), Compassionate Wrath: Transpersonal Approaches to Anger
- ↑ 4 Maccabees
- ↑ Darwin, Charles (1872). The Expression of Emotions in Man and Animals. Note: This book was originally published in 1872, but has been reprinted many times thereafter by different publishers
- ↑ Hare, A. P. (1976). Handbook of small group research (2nd ed.). New York: Free Press, Chapter 3
- ↑ Hare, A. P. (1976). Handbook of small group research (2nd ed.). New York: Free Press, Chapter 7
- ↑ Milgram, S. (1974, ). An interview with Carol Tavris. Psychology Today, pp. 70-73
- ↑ Kemper, T. D. (1978). A social interactional theory of emotion. New York: Wiley
- ↑ Collins, Randall. (2004) Interaction Ritual Chains. Princeton University Press
- ↑ Scheff, Thomas J, and Retzinger, Suzanne. (1991) Emotions and violence : shame and rage in destructive conflicts. Lexington, Mass: Lexington Books
- ↑ Hochschild, A. R. (1983). The managed heart: The commercialization of human feeling. Berkeley: University of California Press
- ↑ Thoits, P. A. (1990). Emotional deviance: research agendas. T. D. Kemper (Ed.), Research agendas in the sociology of emotions (pp. 180–203). Albany: State University of New York Press
- ↑ Ekman, P. & Friesen, W. V (1969). The repertoire of nonverbal behavior: Categories, origins, usage, and encoding. Semiotica, 1, 49–98.
- ↑ Counseling recovery processes - RC website
- ↑ On Emotion - an article from Manchester Gestalt Centre website | Emotion
Template:Emotion
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]
# Overview
An emotion is a "complex reaction pattern, involving experiential, behavioral, and physiological elements, by which the individual attempts to deal with a personally significant matter of event."[1] It arises without conscious effort and is either positive or negative in its valence.
Other closely related terms are:
- affect, a synonym for emotion
- affect display, external display of emotion
- disposition, referring to a durable differentiating characteristic of a person, a tendency to react to situations with a certain emotion
- feeling, which usually refers to the subjective, phenomenological aspect of emotion
- mood, which refers to an emotional state of duration intermediate between an emotion and a disposition
# Etymology
Emotion is derived from French émotion, from émouvoir, 'excite' based on Latin emovere, from e- (variant of ex-) 'out' and movere 'move'. "Motivation" is also derived from movere.
# Definitions of emotion
Emotion is very complex, and the term has no single universally accepted definition.[2] The study of emotions is part of psychology, neuroscience, and ethics.
According to Sloman,[3] emotions are cognitive processes. Some authors emphasize the difference between human emotions and the affective behavior of animals.
We often talk about brains as information-processing systems, but any account of the brain that lacks an account of emotions, motivations, fears, and hopes is incomplete.[citation needed] Emotions are measurable physical responses to salient stimuli: the increased heartbeat and perspiration that accompany fear, the freezing response of a rat in the presence of a cat, or the extra muscle tension that accompanies anger. Feelings, on the other hand, are the subjective experiences that sometimes accompany these processes: the sensations of happiness, envy, sadness, and so on.[citation needed] Emotions seem to employ largely unconscious machinery—for example, brain areas involved in emotion will respond to angry faces that are briefly presented and then rapidly masked, even when subjects are unaware of having seen the face. Across cultures the expression of basic emotions is remarkably similar, and as Darwin observed, it is also similar across all mammals. There are even strong similarities in physiological responses among humans, reptiles, and birds when showing fear, anger, or parental love.[citation needed]
Modern views propose that emotions are brain states that quickly assign value or valence to outcomes and provide a simple plan of action. Thus, emotion can be viewed as a type of computation, a rapid, automatic summary that initiates appropriate actions.[citation needed] When a bear is galloping toward you, the rising fear directs your brain to do the right things (determining an escape route) instead of all the other things it could be doing (rounding out your grocery list). When it comes to perception, you can spot an object more quickly if it is, say, a spider rather than a roll of tape. In the realm of memory, emotional events are laid down differently by a parallel memory system involving a brain area called the amygdala.
One goal of emotional neuroscience is to understand the nature of the many disorders of emotion, depression being the most common and costly. Impulsive aggression and violence are also thought to be consequences of faulty emotion regulation.[citation needed]
# The function of emotion (relations between: Emotion, Meta-emotion, and Reason)
Emotion is generally regarded by Western civilization as the antithesis of reason. This distinction stems from Western philosophy specifically Cartesian dualism and modern interpretations of Stoicism, and is reflected in common phrases like appeal to emotion or your emotions have taken over.[citation needed]
In Paul D. MacLean's Triune brain model, emotions are defined as the responses of the Mammalian cortex. Emotion competes with even more instinctive responses from the Reptilian cortex and the more logical, reasoning neocortex.[citation needed] However, current research on the neural circuitry of emotion suggests that emotion is an essential part of human decision-making and planning, and that the famous distinction made by Descartes between reason and emotion is not as clear as it seems.[4]
Emotions can be undesired either to the individual experiencing them, but also can be undesired to the other persons, groups of persons, organizations, sub-cultures, and civilizations such as Western civilization, which can be viewed as the emotion being subjected to the individual's or someone else's discouraging meta-emotion about the undesired emotion or can be even repressed by the meta-emotions. Thus one of the most distinctive, and perhaps challenging, facts about human beings is this potential for entanglement, or possibly opposition, between emotion, meta-emotion, will, and reason.[citation needed]
Some state that there is no empirical support for any generalization suggesting the antithesis between reason and emotion: indeed, anger or fear can often be thought of as a systematic response to observed facts. In any case, it is clear that the relation between logic and argument and emotion is one which merits careful study.[citation needed]
Emotion as the subject of scientific research has multiple dimensions: behavioral, physiological, subjective, and cognitive. Sloman argues that many emotions are side-effects of the operations of complex mechanisms (e.g. 'alarm' mechanisms) required in animals or machines with multiple motives and limited capacities and resources for coping with a changing and unpredictable world, just as 'thrashing' can sometimes occur as a side-effect of scheduling and memory management mechanisms required in a computer operating system for purposes other than producing thrashing. Such side effects are sometimes useful, but sometimes they are dysfunctional.[citation needed] Other theorists, often influenced by writings of Antonio Damasio argue that emotions themselves are necessary for any intelligent system (natural or artificial).[citation needed]
Psychiatrist William Glasser's theory of the human control system states that behavior is composed of four simultaneous components: deeds, ideas, emotions, and physiological states. He asserts that we choose the idea and deed and that the associated emotions and physiological states also occur but cannot be chosen independently. He calls his construct a total behavior to distinguish it from the common concept of behavior. He uses the verbs to describe what is commonly seen as emotion. For example, he uses 'to depress' to describe the total behavior commonly known as depression which, to him, includes depressing ideas, actions, emotions, and physiological states. Dr. Glasser also further asserts that internal choices (conscious or unconscious) cause emotions instead of external stimuli.[citation needed]
According to Damasio, feeling can be viewed as the subjective experience of an emotion that arises physiologically in the brain.[5]
Many psychologists adopt the ABC model, which defines emotions in terms of three fundamental attributes: A. physiological arousal, B. behavioral expression (e.g. facial expressions), and C. conscious experience, the subjective feeling of an emotion.[citation needed] All three attributes are necessary for a full fledged emotional event, though the intensity of each may vary greatly.[citation needed]
Robert Masters makes the following distinctions between affect, feeling and emotion: "As I define them, affect is an innately structured, non-cognitive evaluative sensation that may or may not register in consciousness; feeling is affect made conscious, possessing an evaluative capacity that is not only physiologically based, but that is often also psychologically (and sometimes relationally) oriented; and emotion is psychosocially constructed, dramatized feeling."[6]
In pop culture there are sub-cultures which cultivate the expressions of anger and rebelliousness even when they are not really angry, its members encouraging each other to express the anger by internalizing meta-gladness about it.
Encouragement (i.e. meta-gladness) and discouragement (i.e. psychological repression) of selected emotions - instead of mere awareness and equal interest in all emotions - can be considered as additional source of organizational climate, family dynamics, psychodynamics, personality traits, and of mental disorders, including depression among others.[citation needed]
## Emotions in the Philosophy of Mind
In opposition to the traditional Philosophy of Mind that has considered emotions only as non-essential addition, at best giving a flavour to rational intellectual thought, the authors of naturalistic Philosophy of Mind inspired by prospects of building robots and other autonomous agents are starting to give emotions a central role as an indispensable constituent for adaptive agency (see DeLancey 2002/2004).[citation needed]
## Emotions in Decision Making
There is increasing support for treating people's emotions as an information source in their decision making process.[citation needed]
## Emotions in Philosophy
What is the relationship between reason and emotion?
4 Maccabees [7] echoes nearly the same idea, and "philosophically" discusses the reason versus emotion in an argument that if reason rules the emotions that prevent self-control, then it may rule the emotions that stop people from acting justly (malice) and courageously (anger, fear and pain), and describes primary emotions using a branching and farming analogy. In short:
Such basic views of emotions have seen the world through thousands of years, leading to ideas like the age of reason, age of enlightenment (ironically scorned by many Christians) and logical positivism, and affecting the history of logic, reason and science from its roots to its latest stems.[citation needed]
Conversely, emotional people experience reason as cold, irrational and evil, despite its benefits. There is no use to proving wrong such meaningless, logic-eschewing beliefs that don't want to or claim to be reasonable.
# Theoretical traditions in Psychogical Emotion Research
Several theoretical traditions in emotion research have been offered. These traditions are not mutually exclusive and many researchers incorporate multiple perspectives in their work.
## Somatic theories
William James in the late 19th century believed that emotional experience is largely due to the experience of bodily changes. These changes might be visceral, postural, or facially expressive. The most basic of these somatic theories is the James-Lange theory. This theory and its derivates state that a changed situation leads to a changed bodily state. It is this bodily state which in turn gives rise to an emotion. Hence the emotion fear upon encountering a bear in the woods would follow from:
This approach underlies experiment where through manipulating the bodily state, a desired emotion is induced (e.g. in laughter therapy).
## The Cannon-Bard theory
Walter Cannon provided empirical evidence against the dominance of the James-Lange theory of the physiological aspects emotions in the second edition of Bodily Changes in Pain, Hunger, Fear and Rage. Cannon and Bard came up with a different account of the relations between emotions and behavior; where a certain situation leads to an emotion; which in turn activates a typical behavior. Here the emotion fear upon encountering a bear in the woods would result in:
## Cognitive theories
Research in social psychology interprets emotions as a combination of two elements; physiological arousal and cognitive interpretation. The earliest account of such a theory is the Singer-Schachter theory that is based on experiments that varied arousal introducing chemical (adrenaline) and put the participants in different situations. The combination of the appraisal of the situation (cognitive) and whether participants received adrenaline or a placebo together determined the response. In the example of the bear this would lead to:
Several other theories have a similar ideas, for example, the framework proposed by Nico Frijda where such appraisal leads to action tendencies is related to this idea.
In all these theories, the different emotions causes a detectable physical response in the body. These responses are often perceived as sensation in the body; for example:
- Fear is felt as a heightened heartbeat, increased “flinch” response, and increased muscle tension.
- Anger, based on sensation, seems indistinguishable from fear.
- Happiness is often felt as an expansive or swelling feeling in the chest and the sensation of lightness or buoyancy, as if standing underwater.
- Sadness is often experienced as a feeling of tightness in the throat and eyes, and relaxation in the arms and legs.
- Shame can be felt as heat in the upper chest and face.
- Desire can be accompanied by a dry throat, heavy breathing, and increased heart rate.
## The evolutionary perspective
A fourth theoretical tradition has been gaining influence once more (see: Cornelius, 1996).
This fourth, evolutionary tradition, started in the late 19th century with Charles Darwin's publication of a book on the expression of emotions in man and animals.[8] Darwin's original thesis was that emotions evolved via natural selection for reasons of warning other creatures about your intentions (e.g. a cat with a high back is angry and will strike you unless you back off). Darwin argued that for mankind emotions were no longer functional but are epiphenomena of functional associated habits. Such an evolutionary origin would predict emotions to be cross-culturally universal. Confirmation of this biological origin was provided by Paul Ekman's seminal research on facial expressions in humans. Other research in this area focuses on physical displays of emotion including body language of animals and facial expressions in humans. (See Affect display.) The increased potential in neuroimaging has allowed investigation of this idea focusing on the working brain itself. Important neurological advances where made from this perspectives in the 1990s by, for example, Joseph LeDoux and Antonio Damasio.
### Primary and secondary emotion
Primary emotions (i.e., innate emotions, such as fear) "depend on limbic system circuitry," with the amygdala and anterior cingulate gyrus being "key players".
- Smell carries directly to limbic areas of the mammalian brain via nerves running from the olfactory bulbs to the septum, amygdala, and hippocampus. In the acquatic brain, olfaction was critical for detecting food, foes, and mates from a distance in murky waters.
- An emotional feeling, like an aroma, has a volatile or "thin-skinned" quality because sensory cells lie on the exposed exterior of the olfactory epithelium (i.e., on the bodily surface itself).
- A sudden scent, like a whiff of smelling salts, may jolt the mind. The force of a mood is reminiscent of a smell's intensity (e.g., soft and gentle, pungent, or overpowering), and similarly permeates and fades as well. The design of emotion cues, in tandem with the forebrain's olfactory prehistory, suggests that the sense of smell is the neurological model for our emotions.
Secondary emotions (i.e., feelings attached to objects [e.g., to dental drills], events, and situations through learning) require additional input, based largely on memory, from the prefrontal and somatosensory cortices. The stimulus may still be processed directly via the amygdala but is now also analyzed in the thought process. Thoughts and emotions are interwoven: every thought, however bland, almost always carries with it some emotional undertone, however subtle.
## Neurobiological theories of emotion
Based on discoveries made through neural mapping of the limbic system, the neurobiological explanation of human emotion is that emotion is a pleasant or unpleasant mental state organized in the limbic system of the mammalian brain.
Defined as such, these emotional states are specific manifestations of non-verbally expressed feelings of agreement, amusement, anger, certainty, control, disagreement, disgust, disliking, embarrassment, fear, guilt, happiness, hate, interest, liking, love, sadness, shame, surprise, and uncertainty. If distinguished from reactive responses of reptiles, emotions would then be mammalian elaborations of general vertebrate arousal patterns, in which neurochemicals (e.g., dopamine, noradrenaline, and serotonin) step-up or step-down the brain's activity level, as visible in body movements, gestures, and postures. In mammals, primates, and human beings, feelings are displayed as emotion cues.
For example, the human emotion of love is proposed to have evolved from paleocircuits of the mammalian brain (specifically, modules of the cingulated gyrus) designed for the care, feeding, and grooming of offspring. Paleocircuits are neural platforms for bodily expression configured millions of years before the advent of cortical circuits for speech. They consist of pre-configured pathways or networks of nerve cells in the forebrain, brain stem and spinal cord. They evolved prior to the earliest mammalian ancestors, as far back as the jawless fishes, to control motor function.
Presumably, before the mammalian brain, life in the non-verbal world was automatic, preconscious, and predictable. The motor centers of reptiles react to sensory cues of vision, sound, touch, chemical, gravity, and motion with pre-set body movements and programmed postures. With the arrival of night-active mammals, circa 180 million years ago, smell replaced vision as the dominant sense, and a different way of responding arose from the olfactory sense, which is proposed to have developed into mammalian emotion and emotional memory. In the Jurassic Period, the mammalian brain invested heavily in olfaction to succeed at night as reptiles slept — one explanation for why olfactory lobes in mammalian brains are proportionally larger than in the reptiles. These odor pathways gradually formed the neural blueprint for what was later to become our limbic brain.
### Brain areas related to emotion
Emotions are thought to be related to activity in brain areas that direct our attention, motivate our behavior, and determine the significance of what is going on around us. Pioneering work by Broca (1878), Papez (1937), and MacLean (1952) suggested that emotion is related to a group of structures in the center of the brain called the limbic system, which includes the hypothalamus, cingulate cortex, hippocampi, and other structures. More recent research has shown that some of these limbic structures are not as directly related to emotion as others are, while some non-limbic structures have been found to be of greater emotional relevance. The following brain structures are currently thought to be most involved in emotion:
- Amygdala — The amygdalae are two small, round structures located anterior to the hippocampi near the temporal poles. The amygdalae are involved in detecting and learning what parts of our surroundings are important and have emotional significance. They are critical for the production of emotion, and may be particularly so for negative emotions, especially fear.
- Prefrontal cortex — The term prefrontal cortex refers to the very front of the brain, behind the forehead and above the eyes. It appears to play a critical role in the regulation of emotion and behavior by anticipating the consequences of our actions. The prefrontal cortex may play an important role in delayed gratification by maintaining emotions over time and organizing behavior toward specific goals.
- Anterior cingulate — The anterior cingulate cortex (ACC) is located in the middle of the brain, just behind the prefrontal cortex. The ACC is thought to play a central role in attention, and may be particularly important with regard to conscious, subjective emotional awareness. This region of the brain may also play an important role in the initiation of motivated behavior.
- Ventral striatum — The ventral striatum is a group of subcortical structures thought to play an important role in emotion and behavior. One part of the ventral striatum called the nucleus accumbens is thought to be involved in the experience of goal-directed positive emotion. Individuals with addictions experience increased activity in this area when they encounter the object of their addiction.
- Insula — The insular cortex is thought to play a critical role in the bodily experience of emotion, as it is connected to other brain structures that regulate the body’s autonomic functions (heart rate, breathing, digestion, etc.). This region also processes taste information and is thought to play an important role in experiencing the emotion of disgust.
### Positive and negative perception
Like aromas, emotions are experienced as either positive or negative, pleasant or unpleasant; emotions do not seem to be neutral. Like odors, feelings come and go, but are logical, and clearly show upon our face in mood signs. It is likely that many emotions evolved from aroma paleocircuits a. in subcortical nuclei (e.g., the paleocortex of the amygdala), and b. in layers of nerve cells within the forebrain's outer covering of neocortex. The latter's stratified architecture resembles that of the olfactory bulb, which is organized in layers as well.
# Sociology of Emotions
Systematic observations of group interaction found that a substantial portion of group activity is devoted to the socio-emotional issues of expressing affect and dealing with tension.[9] Simultaneously, field studies of social attraction in groups revealed that feelings of individuals about each other collate into social networks,[10] a discovery that still is being explored in the field of social network analysis.
Ethnomethodology revealed emotional commitments to everyday norms through purposeful breaching of the norms. For example, students acting as boarders in their own homes reported others' astonishment, bewilderment, shock, anxiety, embarrassment, and anger; family members accused the students of being mean, inconsiderate, selfish, nasty, or impolite. Actors who breach a norm themselves feel waves of emotion, including apprehension, panic, and despair.[11] However, habitual rule breaking leads to declining stress, and may eventually end in enjoyment.
T. David Kemper[12] proposed that people in social interaction have positions on two relational dimensions: status and power. Emotions emerge as interpersonal events change or maintain individuals' status and power. For example, affirming someone else's exalted status produces love-related emotions. Increases or decreases in one's own and other's status or power generate specific emotions whose quality depends on the patterns of change.
Sociologist Randall Collins has stated that emotional energy is the main motivating force in social life, for love and hatred, investing, working or consuming, rendering cult or waging war.[13] Emotional energy ranges from the highest heights of enthusiasm, self-confidence and initiative to the deepest depths of apathy, depression and retreat. Emotional energy comes from variously successful or failed chains of interaction rituals, that is, patterned social encounters –from conversation or sexual flirtation through Christmas family dinners or office work to mass demonstrations, organizations or revolutions. In the latter, the coupling of participants' behavior synchronizes their nervous systems to the point of generating a collective effervescence, one observable in their mutual focus and emotional entraining, as well as in their loading of emotional and symbolic meaning to entities which subsequently become emblems of the ritual and of the membership group endorsing, preserving, promoting and defending them. Thus social life would be most importantly about generating and distributing emotional energy.
Thomas J. Scheff[14] established that many cases of social conflict are based on a destructive and often escalating, but stoppable and reversible shame-rage cycle: when someone results or feels shamed by another, their social bond comes under stress. This can be cooperatively acknowledged, talked about and – most effectively when possible - laughed at so their social bond may be restored. Yet, when shame is not acknowledged, but instead negated and repressed, it becomes rage, and rage may drive to aggressive and shaming actions that feed-back negatively on this self-destructive situation. The social management of emotions might be the fundamental dynamics of social cooperation and conflict around resources, complexity, conflict and moral life. It is well-established sociological fact that expression and feeling of the emotion of anger, for example, is strongly discouraged (repressed) in girls and women in many cultures, while fear is discouraged in boys and men. Some cultures and sub-cultures encourage or discourage happiness, sadness, jealousy, excitedness, and many other emotions. The free expression of the emotion of disgust is considered socially unacceptable in many countries.
Arlie Hochschild[15] proposed that individuals apply cultural and ideological standards to judge the suitability of emotions occurring during a social interaction, and then manage their feelings to produce acceptable displays. Hochschild showed that jobs often require such emotional labor. Her classic study of emotional labor among flight attendants found that an industry speed-up, reducing contact between flight attendants and passengers, made it impossible for flight attendants to deliver authentic emotional labor, so they ended up surface-acting superficial smiles. Peggy Thoits[16] divided emotion management techniques into implementation of new events and reinterpretation of past events. Thoits noted that emotions also can be managed with drugs, by performing faux gestures and facial expressions, or by cognitive reclassifications of one's feelings.
Affect Control Theory which was originated by David R. Heise proposes that social actions are designed by their agents to create impressions that befit sentiments reigning in a situation. Emotions are transient personal states depending on the current impression of the emoting person, and on the comparison of that impression with the sentiment attached to the person's identity.
# Classification of emotions
There has been considerable debate whether emotions should be classified as a position in a continuum (e.g. the circumplex model by Russell, or many of the valence approaches in social psychology) or whether emotions are best identified as distinct (basic) states.
## Classification by basic emotions
One of the most influential classification approaches in the study of emotion is Robert Plutchik’s classification into eight primary emotions. The emotions that Plutchik lists as primary are:[citation needed]
- anger
- fear
- sadness
- joy
- disgust
- curiosity/interest
- surprise
- acceptance
Similar to the way primary colors combine, primary emotions are believed to blend together to form the full spectrum of human emotional experience. Plutchik reasons that these eight are primary on evolutionary grounds, by relating each to behavior with survival value. For example: fear motivates flight from danger, anger motivates fighting for survival. They are considered to be part of our biological heritage and built into human nature.[citation needed]
Paul Ekman devised a similar list of basic emotions from cross-cultural research on the Fore tribesmen of Papua New Guinea. He found that even members of an isolated, stone age culture could reliably identify the expressions of emotion in photographs of people from cultures which the Fore were not yet familiar, and concluded that the facial expression of some basic emotions is innate. The following is Ekman’s list of basic emotions:[citation needed]
- anger
- fear
- sadness
- happiness
- disgust
Ekman holds that this lends further support to the view that at least some emotions are primary, innate, and universal in all human beings.[17]
Lazarus (1991) similarly offers a taxonomy of 'Core Relational Themes' for various emotions; these help define both function and eliciting conditions. They include a demeaning offense against me and mine for anger; facing an immediate, concrete, and overwhelming physical danger for fear; having experienced an irrevocable loss for sadness; taking in or being too close to an indigestible object or idea (metaphorically speaking) for disgust; making reasonable progress toward the realization of a goal for happiness.
# Emotions and Psychotherapy
Depending on the particular school's general emphasize either on cognitive component of emotion, physical energy discharging, or on symbolic movement and facial expression components of emotion, different schools of psychotherapy approach human emotions differently. While, for example, the school of Re-evaluation Counseling propose that distressing emotions are to be relieved by “discharging” them - hence crying, laughing, sweating, shaking, and trembling.[18] other more cognitively oriented schools approach them via their cognitive components, or via symbolic movement and facial expression components (like in contemporary Gestalt therapy[19]).
# Meta-emotions
Meta-emotion refers in accordance with the general definition of the prefix "meta-" to second-order emotions about first-order emotions. Meta-emotions can be short-lived or long-lived. The latter can be a source of discouragement or even psychological repression, or encouragement of specific emotions, having implications for personality traits, psychodynamics, organizational climate, emotional disorders, but also emotional awareness, and emotional intelligence.
# Emotions and computer models, artificial intelligence and computing
A flurry of recent work in computer science, engineering, psychology and neuroscience is aimed at developing devices that recognize human affect display and modelling emotions generally (Fellous, Armony & LeDoux, 2002).
# Emotion in animals
Animals have physiological responses that are analogous to human emotional responses, as has been recognized at least since Darwin published The Expression of Emotions in Man and Animals in 1872.
# Notes
- ↑ vandenBos, Gary B. (2006). APA Dictionary of Psychology. Washington, DC: American Psychological Association
- ↑ Emotional Competency discussion of emotion
- ↑ Sloman, Aaron (1981) Why Robots Will Have Emotions. In proc.[1]. University of Sussex, UK
- ↑ Damasio, Antonio (1994) Descartes Error Penguin Putnam, New York, New York
- ↑ Damasio, Antonio (1994) Descartes Error Penguin Putnam, New York, New York
- ↑ Masters, Robert (2000), Compassionate Wrath: Transpersonal Approaches to Anger
- ↑ 4 Maccabees
- ↑ Darwin, Charles (1872). The Expression of Emotions in Man and Animals. Note: This book was originally published in 1872, but has been reprinted many times thereafter by different publishers
- ↑ Hare, A. P. (1976). Handbook of small group research (2nd ed.). New York: Free Press, Chapter 3
- ↑ Hare, A. P. (1976). Handbook of small group research (2nd ed.). New York: Free Press, Chapter 7
- ↑ Milgram, S. (1974, ). An interview with Carol Tavris. Psychology Today, pp. 70-73
- ↑ Kemper, T. D. (1978). A social interactional theory of emotion. New York: Wiley
- ↑ Collins, Randall. (2004) Interaction Ritual Chains. Princeton University Press
- ↑ Scheff, Thomas J, and Retzinger, Suzanne. (1991) Emotions and violence : shame and rage in destructive conflicts. Lexington, Mass: Lexington Books
- ↑ Hochschild, A. R. (1983). The managed heart: The commercialization of human feeling. Berkeley: University of California Press
- ↑ Thoits, P. A. (1990). Emotional deviance: research agendas. T. D. Kemper (Ed.), Research agendas in the sociology of emotions (pp. 180–203). Albany: State University of New York Press
- ↑ Ekman, P. & Friesen, W. V (1969). The repertoire of nonverbal behavior: Categories, origins, usage, and encoding. Semiotica, 1, 49–98.
- ↑ Counseling recovery processes - RC website
- ↑ On Emotion - an article from Manchester Gestalt Centre website | https://www.wikidoc.org/index.php/Emotion | |
dbab4bc17dea33ebf9078ff1da8b03ab56162273 | wikidoc | Emu oil | Emu oil
Emu oil is an oil made from refined fat of the Emu, a bird native to Australia. It has been used for over 1000 years by the Australian aborigines in the treatment of burns,cut wounds,bruise and as a pain reliever for bone muscle and joints disorder. Emu oil is approximately 70% unsaturated fatty acids. The largest component is oleic acid – a mono-unsaturated fatty acid. Emu oil also contains about 20% linoleic (Omega 6) acid and 1-2% linolenic (Omega 3) acid. There is some evidence to suggest that the oil may have medicinal benefit. It is frequently used topically to soften skin and is frequently found in ointments for dry cracked heels.
Emu oil has been shown in studies to aid in reducing scar formation in healed burned wounds,muscle sprain and arthritis, due to its strong anti-inflammatory properties.
Emu oil is a complete neutral lipid, since emu oil lacks phospholipid, making it highly penetrating to the skin. | Emu oil
Emu oil is an oil made from refined fat of the Emu, a bird native to Australia. It has been used for over 1000 years by the Australian aborigines in the treatment of burns,cut wounds,bruise and as a pain reliever for bone muscle and joints disorder.[citation needed] Emu oil is approximately 70% unsaturated fatty acids. The largest component is oleic acid – a mono-unsaturated fatty acid. Emu oil also contains about 20% linoleic (Omega 6) acid and 1-2% linolenic (Omega 3) acid. There is some evidence to suggest that the oil may have medicinal benefit.[1] It is frequently used topically to soften skin and is frequently found in ointments for dry cracked heels.
Emu oil has been shown in studies to aid in reducing scar formation in healed burned wounds,muscle sprain and arthritis, due to its strong anti-inflammatory properties.
Emu oil is a complete neutral lipid, since emu oil lacks phospholipid, making it highly penetrating to the skin.[2][3] | https://www.wikidoc.org/index.php/Emu_oil | |
a2384042ba736127cb07f6a35baff438d5df29f9 | wikidoc | Enamine | Enamine
An enamine is an unsaturated compound derived by the reaction of an aldehyde or ketone with a secondary amine followed by loss of H2O.
The word "enamine" is apparently derived from the prefix en-, used as the suffix of alkene, and the root amine. Compare with enol, which is a molecule containing both alkene (en-) and alcohol (-ol).
If one of the nitrogen substituents is H, it is the tautomeric form of an imine. This usually will rearrange to the imine; however there are several exceptions (such as aniline). The enamine-imine tautormerism may be considered analogous to the keto-enol tautomerism. In both cases, a hydrogen atom switches its location between the heteroatom (oxygen or nitrogen) and the second carbon atom.
# Form
R_2C=CR-NR_2 | Enamine
An enamine is an unsaturated compound derived by the reaction of an aldehyde or ketone with a secondary amine followed by loss of H2O.
The word "enamine" is apparently derived from the prefix en-, used as the suffix of alkene, and the root amine. Compare with enol, which is a molecule containing both alkene (en-) and alcohol (-ol).[citation needed]
If one of the nitrogen substituents is H, it is the tautomeric form of an imine. This usually will rearrange to the imine; however there are several exceptions (such as aniline). The enamine-imine tautormerism may be considered analogous to the keto-enol tautomerism. In both cases, a hydrogen atom switches its location between the heteroatom (oxygen or nitrogen) and the second carbon atom.
# Form
<math>R_2C=CR-NR_2</math> | https://www.wikidoc.org/index.php/Enamine | |
c2f71d2efdc8b99a54ec73382f1b958bd6523491 | wikidoc | Enaptin | Enaptin
Enaptin also known as nesprin-1 or synaptic nuclear envelope protein 1 (syne-1) is an actin-binding protein that in humans that is encoded by the SYNE1 gene.
# Function
This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane.
Enaptin is a nuclear envelope protein found in human myocytes and synapses, which is made up of 8,797 amino acids. Enaptin is involved in the maintenance of nuclear organization and structural integrity, tethering the cell nucleus to the cytoskeleton by interacting with the nuclear envelope and with F-actin in the cytoplasm.
# Structure
Enaptin contains a coiled alpha-helical region and a large beta-sheet region in the upper part and at least four alpha-helices spliced together, indicating the similarity with collagen. The protein is made up of three main parts, as can be seen in the diagram: cytoplasmic (1-8746), anchor for type IV membrane protein (8747-8767), and the sequence for perinuclear space (8768-8797). The region in the perinuclear space contains a KASH domain.
The molecular weight of the mature protein is approximately 1,011 kDa, and it has a theoretical pI of 5.38. The protein's chemical formula is C44189H71252N12428O14007S321. It has a theoretical Instability Index (II) of 51.63, indicating that it would be unstable in a test tube. The protein's in vivo half-life, the time it takes for half of the amount of protein in a cell to disappear after its synthesis in the cell, is predicted to be approximately 30 hours (in mammalian reticulocytes).
# Clinical significance
Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia 8, also referred to as autosomal recessive cerebellar ataxia type 1 or recessive ataxia of Beauce. | Enaptin
Enaptin also known as nesprin-1 or synaptic nuclear envelope protein 1 (syne-1) is an actin-binding protein that in humans that is encoded by the SYNE1 gene.[1]
# Function
This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane.[1]
Enaptin is a nuclear envelope protein found in human myocytes and synapses, which is made up of 8,797 amino acids. Enaptin is involved in the maintenance of nuclear organization and structural integrity, tethering the cell nucleus to the cytoskeleton by interacting with the nuclear envelope and with F-actin in the cytoplasm.
# Structure
Enaptin contains a coiled alpha-helical region and a large beta-sheet region in the upper part and at least four alpha-helices spliced together, indicating the similarity with collagen. The protein is made up of three main parts, as can be seen in the diagram: cytoplasmic (1-8746), anchor for type IV membrane protein (8747-8767), and the sequence for perinuclear space (8768-8797). The region in the perinuclear space contains a KASH domain.
The molecular weight of the mature protein is approximately 1,011 kDa, and it has a theoretical pI of 5.38.[2] The protein's chemical formula is C44189H71252N12428O14007S321. It has a theoretical Instability Index (II) of 51.63, indicating that it would be unstable in a test tube. The protein's in vivo half-life, the time it takes for half of the amount of protein in a cell to disappear after its synthesis in the cell, is predicted to be approximately 30 hours (in mammalian reticulocytes).[3]
# Clinical significance
Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia 8, also referred to as autosomal recessive cerebellar ataxia type 1 or recessive ataxia of Beauce.[1] | https://www.wikidoc.org/index.php/Enaptin | |
7454ba2883610cdb6198cdbf7c608854cacdf1ba | wikidoc | Mitosis | Mitosis
# Overview
Mitosis is the process by which a cell duplicates the chromosomes in its cell nucleus, in order to generate two, identical, daughter nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two daughter cells containing roughly equal shares of these cellular components. Mitosis and cytokinesis together define the mitotic (M) phase of the cell cycle, the division of the mother cell into two daughter cells, each with the genetic equivalent of the parent cell.
Mitosis occurs exclusively in eukaryotic cells, but occurs in different ways in different species. For example, animals undergo an "open" mitosis, where the nuclear envelope breaks down before the chromosomes separate, while yeast such as Saccharomyces cerevisiae and fungi such as Aspergillus nidulans undergo a "closed" mitosis, where chromosomes divide within an intact cell nucleus. In multicellular organisms, the somatic cells undergo mitosis, while germ cells — cells destined to become sperm in males or ova in females — divide by a related process called meiosis. Prokaryotic cells, which lack a nucleus, divide by a process called binary fission.
The process of mitosis is complex and highly regulated. The sequence of events is divided into phases, corresponding to the completion of one set of activities and the start of the next. These stages are prophase, prometaphase, metaphase, anaphase and telophase. During the process of mitosis the pairs of chromosomes condense and attach to fibers that pull the sister chromatids to opposite sides of the cell. The cell then divides in cytokinesis, to produce two identical daughter cells.
Because cytokinesis usually occurs in conjunction with mitosis, "mitosis" is often used interchangeably with "mitotic phase". However, there are many cells where mitosis and cytokinesis occur separately, forming single cells with multiple nuclei. This occurs most notably among the fungi and slime moulds, but is found in various different groups. Even in animals, cytokinesis and mitosis may occur independently, for instance during certain stages of fruit fly embryonic development. Errors in mitosis can either kill a cell through apoptosis or cause mutations that may lead to cancer.
The primary result of mitosis is the division of the parent cell's genome into two daughter cells. The genome is composed of a number of chromosomes, complexes of tightly-coiled DNA that contain genetic information vital for proper cell function. Because each resultant daughter cell should be genetically identical to the parent cell, the parent cell must make a copy of each chromosome before mitosis. This occurs during S phase, in interphase, the period that precedes the mitotic phase in the cell cycle where preparation for mitosis occurs.
Each new chromosome now contains two identical copies of itself, called sister chromatids, attached together in a specialized region of the chromosome known as the centromere. Each sister chromatid is not considered a chromosome in itself, and a chromosome does not always contain two sister chromatids.
In most eukaryotes, the nuclear envelope that separates the DNA from the cytoplasm disassembles. The chromosomes align themselves in a line spanning the cell. Microtubules, essentially miniature strings, splay out from opposite ends of the cell and shorten, pulling apart the sister chromatids of each chromosome. As a matter of convention, each sister chromatid is now considered a chromosome, so they are renamed to sister chromosomes. As the cell elongates, corresponding sister chromosomes are pulled toward opposite ends. A new nuclear envelope forms around the separated sister chromosomes.
As mitosis completes cytokinesis is well underway. In animal cells, the cell pinches inward where the imaginary line used to be, (the pinching of the cell membrane to form the two daughter cells is called cleavage furrow) separating the two developing nuclei. In plant cells, the daughter cells will construct a new dividing cell wall between each other. Eventually, the mother cell will be split in half, giving rise to two daughter cells, each with an equivalent and complete copy of the original genome.
Prokaryotic cells undergo a process similar to mitosis called binary fission. However, prokaryotes cannot be properly said to undergo mitosis because they lack a nucleus and only have a single chromosome with no centromere.
# Phases
## Interphase
The mitotic phase is a relatively short period of the cell cycle. It alternates with the much longer interphase, where the cell prepares itself for cell division. Interphase is divided into three phases, G1 (first gap), S (synthesis), and G2 (second gap). During all three phases, the cell grows by producing proteins and cytoplasmic organelles. However, chromosomes are replicated only during the S phase. Thus, a cell grows (G1), continues to grow as it duplicates its chromosomes (S), grows more and prepares for mitosis (G2), and divides (M).
## Preprophase
In plant cells only, prophase is preceded by a pre-prophase stage. In highly vacuolated plant cells, the nucleus has to migrate into the center of the cell before mitosis can begin. This is achieved through the formation of a phragmosome, a transverse sheet of cytoplasm that bisects the cell along the future plane of cell division. In addition to phragmosome formation, preprophase is characterized by the formation of a ring of microtubules and actin filaments (called preprophase band) underneath the plasmamembrane around the equatorial plane of the future mitotic spindle and predicting the position of cell plate fusion during telophase. The cells of higher plants (such as the flowering plants) lack centrioles. Instead, spindle microtubules aggregate on the surface of the nuclear envelope during prophase. The preprophase band disappears during nuclear envelope disassembly and spindle formation in prometaphase.
## Prophase
Normally, the genetic material in the nucleus is in a loosely bundled coil called chromatin. At the onset of prophase, chromatin condenses together into a highly ordered structure called a chromosome. Since the genetic material has already been duplicated earlier in S phase, the replicated chromosomes have two sister chromatids, bound together at the centromere by the cohesion complex. Chromosomes are visible at high magnification through a light microscope.
Close to the nucleus are two centrosomes. Each centrosome, which was replicated earlier independent of mitosis, acts as a coordinating center for the cell's microtubules. The two centrosomes nucleate microtubules (which may be thought of as cellular ropes or poles) by polymerizing soluble tubulin present in the cytoplasm. Molecular motor proteins create repulsive forces that will push the centrosomes to opposite side of the nucleus. The centrosomes are only present in animals. In plants the microtubules form independently.
Some centrosomes contain a pair of centrioles that may help organize microtubule assembly, but they are not essential to formation of the mitotic spindle.
## Prometaphase
The nuclear envelope disassembles and microtubules invade the nuclear space. This is called open mitosis, and it occurs in most multicellular organisms. Fungi and some protists, such as algae or trichomonads, undergo a variation called closed mitosis where the spindle forms inside the nucleus or its microtubules are able to penetrate an intact nuclear envelope.
Each chromosome forms two kinetochores at the centromere, one attached at each chromatid. A kinetochore is a complex protein structure that is analogous to a ring for the microtubule hook; it is the point where microtubules attach themselves to the chromosome. Although the kinetochore structure and function are not fully understood, it is known that it contains some form of molecular motor. When a microtubule connects with the kinetochore, the motor activates, using energy from ATP to "crawl" up the tube toward the originating centrosome. This motor activity, coupled with polymerisation and depolymerisation of microtubules, provides the pulling force necessary to later separate the chromosome's two chromatids.
When the spindle grows to sufficient length, kinetochore microtubules begin searching for kinetochores to attach to. A number of nonkinetochore microtubules find and interact with corresponding nonkinetochore microtubules from the opposite centrosome to form the mitotic spindle. Prometaphase is sometimes considered part of prophase.
## Metaphase
As microtubules find and attach to kinetochores in prometaphase, the centromeres of the chromosomes convene along the metaphase plate or equatorial plane, an imaginary line that is equidistant from the two centrosome poles. This even alignment is due to the counterbalance of the pulling powers generated by the opposing kinetochores, analogous to a tug-of-war between equally strong people. In certain types of cells, chromosomes do not line up at the metaphase plate and instead move back and forth between the poles randomly, only roughly lining up along the midline. Metaphase comes from the Greek μετα meaning "after."
Because proper chromosome separation requires that every kinetochore be attached to a bundle of microtubules (spindle fibers) , it is thought that unattached kinetochores generate a signal to prevent premature progression to anaphase without all chromosomes being aligned. The signal creates the mitotic spindle checkpoint.
## Anaphase
When every kinetochore is attached to a cluster of microtubules and the chromosomes have lined up along the metaphase plate, the cell proceeds to anaphase (from the Greek ανα meaning “up,” “against,” “back,” or “re-”).
Two events then occur; First, the proteins that bind sister chromatids together are cleaved, allowing them to separate. These sister chromatids turned sister chromosomes are pulled apart by shortening kinetochore microtubules and move toward the respective centrosomes to which they are attached.
Next, the nonkinetochore microtubules elongate, pushing the centrosomes (and the set of chromosomes to which they are attached) apart to opposite ends of the cell.
These two stages are sometimes called early and late anaphase. Early anaphase is usually defined as the separation of the sister chromatids, while late anaphase is the elongation of the microtubules and the microtubules being pulled farther apart. At the end of anaphase, the cell has succeeded in separating identical copies of the genetic material into two distinct populations.
## Telophase
Telophase (from the Greek τελος meaning "end") is a reversal of prophase and prometaphase events. It "cleans up" the after effects of mitosis. At telophase, the nonkinetochore microtubules continue to lengthen, elongating the cell even more. Corresponding sister chromosomes attach at opposite ends of the cell. A new nuclear envelope, using fragments of the parent cell's nuclear membrane, forms around each set of separated sister chromosomes. Both sets of chromosomes, now surrounded by new nuclei, unfold back into chromatin. Mitosis is complete, but cell division is not yet complete.
## Cytokinesis
Cytokinesis is often mistakenly thought to be the final part of telophase, however cytokinesis is a separate process that begins at the same time as telophase. Cytokinesis is technically not even a phase of mitosis, but rather a separate process, necessary for completing cell division. In animal cells, a cleavage furrow (pinch) containing a contractile ring develops where the metaphase plate used to be, pinching off the separated nuclei. In both animal and plant cells, cell division is also driven by vesicles derived from the Golgi apparatus, which move along microtubules to the middle of the cell. In plants this structure coalesces into a cell plate at the center of the phragmoplast and develops into a cell wall, separating the two nuclei. The phragmoplast is a microtubule structure typical for higher plants, whereas some green algae use a phycoplast microtubule array during cytokinesis. Each daughter cell has a complete copy of the genome of its parent cell. The end of cytokinesis marks the end of the M-phase.
# Significance
The importance of mitosis is the maintenance of the chromosomal set; each cell formed receives chromosomes that are alike in composition and equal in number to the chromosomes of the parent cell. Transcription is generally believed to cease during mitosis, but epigenetic mechanisms such as bookmarking function during this stage of the cell cycle to ensure that the "memory" of which genes were active prior to entry into mitosis are transmitted to the daughter cells.
# Consequences of errors
Although errors in mitosis are rare, the process may go wrong, especially during early cellular divisions in the zygote. Mitotic errors can be especially dangerous to the organism because future offspring from this parent cell will carry the same disorder.
In non-disjunction, a chromosome may fail to separate during anaphase. One daughter cell will receive both sister chromosomes and the other will receive none. This results in the former cell having three chromosomes coding for the same thing (two sisters and a homologue), a condition known as trisomy, and the latter cell having only one chromosome (the homologous chromosome), a condition known as monosomy. These cells are considered aneuploidic cells and these abnormal cells can cause cancer.
Mitosis is a traumatic process. The cell goes through dramatic changes in ultrastructure, its organelles disintegrate and reform in a matter of hours, and chromosomes are jostled constantly by probing microtubules. Occasionally, chromosomes may become damaged. An arm of the chromosome may be broken and the fragment lost, causing deletion. The fragment may incorrectly reattach to another, non-homologous chromosome, causing translocation. It may reattach to the original chromosome, but in reverse orientation, causing inversion. Or, it may be treated erroneously as a separate chromosome, causing chromosomal duplication. The effect of these genetic abnormalities depend on the specific nature of the error. It may range from no noticeable effect, cancer induction, or organism death.
# Endomitosis
Endomitosis is a variant of mitosis without nuclear or cellular division, resulting in cells with many copies of the same chromosome occupying a single nucleus. This process may also be referred to as endoreduplication and the cells as endoploid. An example of endomitosis would be what occurs in megakaryocytes to generate platelets within its cytoplasm.
# Timeline in pictures
Real mitotic cells can be visualized through the microscope by staining them with fluorescent antibodies and dyes. These light micrographs are included below.
- Early prometaphase: The nuclear membrane has just degraded, allowing the microtubules to quickly interact with the kinetochores on the chromosomes, which have just condensed.
- Late metaphase: The centrosomes have moved to the poles of the cell and have established the mitotic spindle. The chromosomes, in light blue, have all assembled at the metaphase plate, except for one.
Late metaphase: The centrosomes have moved to the poles of the cell and have established the mitotic spindle. The chromosomes, in light blue, have all assembled at the metaphase plate, except for one.
- Anaphase: Lengthening nonkinetochore microtubules push the two sets of chromosomes further apart. | Mitosis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Mitosis is the process by which a cell duplicates the chromosomes in its cell nucleus, in order to generate two, identical, daughter nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two daughter cells containing roughly equal shares of these cellular components. Mitosis and cytokinesis together define the mitotic (M) phase of the cell cycle, the division of the mother cell into two daughter cells, each with the genetic equivalent of the parent cell.
Mitosis occurs exclusively in eukaryotic cells, but occurs in different ways in different species. For example, animals undergo an "open" mitosis, where the nuclear envelope breaks down before the chromosomes separate, while yeast such as Saccharomyces cerevisiae and fungi such as Aspergillus nidulans undergo a "closed" mitosis, where chromosomes divide within an intact cell nucleus.[1] In multicellular organisms, the somatic cells undergo mitosis, while germ cells — cells destined to become sperm in males or ova in females — divide by a related process called meiosis. Prokaryotic cells, which lack a nucleus, divide by a process called binary fission.
The process of mitosis is complex and highly regulated. The sequence of events is divided into phases, corresponding to the completion of one set of activities and the start of the next. These stages are prophase, prometaphase, metaphase, anaphase and telophase. During the process of mitosis the pairs of chromosomes condense and attach to fibers that pull the sister chromatids to opposite sides of the cell. The cell then divides in cytokinesis, to produce two identical daughter cells.
Because cytokinesis usually occurs in conjunction with mitosis, "mitosis" is often used interchangeably with "mitotic phase". However, there are many cells where mitosis and cytokinesis occur separately, forming single cells with multiple nuclei. This occurs most notably among the fungi and slime moulds, but is found in various different groups. Even in animals, cytokinesis and mitosis may occur independently, for instance during certain stages of fruit fly embryonic development.[2] Errors in mitosis can either kill a cell through apoptosis or cause mutations that may lead to cancer.
The primary result of mitosis is the division of the parent cell's genome into two daughter cells. The genome is composed of a number of chromosomes, complexes of tightly-coiled DNA that contain genetic information vital for proper cell function. Because each resultant daughter cell should be genetically identical to the parent cell, the parent cell must make a copy of each chromosome before mitosis. This occurs during S phase, in interphase, the period that precedes the mitotic phase in the cell cycle where preparation for mitosis occurs.[3]
Each new chromosome now contains two identical copies of itself, called sister chromatids, attached together in a specialized region of the chromosome known as the centromere. Each sister chromatid is not considered a chromosome in itself, and a chromosome does not always contain two sister chromatids.
In most eukaryotes, the nuclear envelope that separates the DNA from the cytoplasm disassembles. The chromosomes align themselves in a line spanning the cell. Microtubules, essentially miniature strings, splay out from opposite ends of the cell and shorten, pulling apart the sister chromatids of each chromosome.[4] As a matter of convention, each sister chromatid is now considered a chromosome, so they are renamed to sister chromosomes. As the cell elongates, corresponding sister chromosomes are pulled toward opposite ends. A new nuclear envelope forms around the separated sister chromosomes.
As mitosis completes cytokinesis is well underway. In animal cells, the cell pinches inward where the imaginary line used to be, (the pinching of the cell membrane to form the two daughter cells is called cleavage furrow) separating the two developing nuclei. In plant cells, the daughter cells will construct a new dividing cell wall between each other. Eventually, the mother cell will be split in half, giving rise to two daughter cells, each with an equivalent and complete copy of the original genome.
Prokaryotic cells undergo a process similar to mitosis called binary fission. However, prokaryotes cannot be properly said to undergo mitosis because they lack a nucleus and only have a single chromosome with no centromere.[5]
# Phases
## Interphase
The mitotic phase is a relatively short period of the cell cycle. It alternates with the much longer interphase, where the cell prepares itself for cell division. Interphase is divided into three phases, G1 (first gap), S (synthesis), and G2 (second gap). During all three phases, the cell grows by producing proteins and cytoplasmic organelles. However, chromosomes are replicated only during the S phase. Thus, a cell grows (G1), continues to grow as it duplicates its chromosomes (S), grows more and prepares for mitosis (G2), and divides (M).[3]
## Preprophase
In plant cells only, prophase is preceded by a pre-prophase stage. In highly vacuolated plant cells, the nucleus has to migrate into the center of the cell before mitosis can begin. This is achieved through the formation of a phragmosome, a transverse sheet of cytoplasm that bisects the cell along the future plane of cell division. In addition to phragmosome formation, preprophase is characterized by the formation of a ring of microtubules and actin filaments (called preprophase band) underneath the plasmamembrane around the equatorial plane of the future mitotic spindle and predicting the position of cell plate fusion during telophase. The cells of higher plants (such as the flowering plants) lack centrioles. Instead, spindle microtubules aggregate on the surface of the nuclear envelope during prophase. The preprophase band disappears during nuclear envelope disassembly and spindle formation in prometaphase.[6]
## Prophase
Normally, the genetic material in the nucleus is in a loosely bundled coil called chromatin. At the onset of prophase, chromatin condenses together into a highly ordered structure called a chromosome. Since the genetic material has already been duplicated earlier in S phase, the replicated chromosomes have two sister chromatids, bound together at the centromere by the cohesion complex. Chromosomes are visible at high magnification through a light microscope.
Close to the nucleus are two centrosomes. Each centrosome, which was replicated earlier independent of mitosis, acts as a coordinating center for the cell's microtubules. The two centrosomes nucleate microtubules (which may be thought of as cellular ropes or poles) by polymerizing soluble tubulin present in the cytoplasm. Molecular motor proteins create repulsive forces that will push the centrosomes to opposite side of the nucleus. The centrosomes are only present in animals. In plants the microtubules form independently.
Some centrosomes contain a pair of centrioles that may help organize microtubule assembly, but they are not essential to formation of the mitotic spindle.[7]
## Prometaphase
The nuclear envelope disassembles and microtubules invade the nuclear space. This is called open mitosis, and it occurs in most multicellular organisms. Fungi and some protists, such as algae or trichomonads, undergo a variation called closed mitosis where the spindle forms inside the nucleus or its microtubules are able to penetrate an intact nuclear envelope.[8][9]
Each chromosome forms two kinetochores at the centromere, one attached at each chromatid. A kinetochore is a complex protein structure that is analogous to a ring for the microtubule hook; it is the point where microtubules attach themselves to the chromosome.[10] Although the kinetochore structure and function are not fully understood, it is known that it contains some form of molecular motor.[11] When a microtubule connects with the kinetochore, the motor activates, using energy from ATP to "crawl" up the tube toward the originating centrosome. This motor activity, coupled with polymerisation and depolymerisation of microtubules, provides the pulling force necessary to later separate the chromosome's two chromatids.[11]
When the spindle grows to sufficient length, kinetochore microtubules begin searching for kinetochores to attach to. A number of nonkinetochore microtubules find and interact with corresponding nonkinetochore microtubules from the opposite centrosome to form the mitotic spindle.[12] Prometaphase is sometimes considered part of prophase.
## Metaphase
As microtubules find and attach to kinetochores in prometaphase, the centromeres of the chromosomes convene along the metaphase plate or equatorial plane, an imaginary line that is equidistant from the two centrosome poles.[12] This even alignment is due to the counterbalance of the pulling powers generated by the opposing kinetochores, analogous to a tug-of-war between equally strong people. In certain types of cells, chromosomes do not line up at the metaphase plate and instead move back and forth between the poles randomly, only roughly lining up along the midline. Metaphase comes from the Greek μετα meaning "after."
Because proper chromosome separation requires that every kinetochore be attached to a bundle of microtubules (spindle fibers) , it is thought that unattached kinetochores generate a signal to prevent premature progression to anaphase[2] without all chromosomes being aligned. The signal creates the mitotic spindle checkpoint.[13]
## Anaphase
When every kinetochore is attached to a cluster of microtubules and the chromosomes have lined up along the metaphase plate, the cell proceeds to anaphase (from the Greek ανα meaning “up,” “against,” “back,” or “re-”).
Two events then occur; First, the proteins that bind sister chromatids together are cleaved, allowing them to separate. These sister chromatids turned sister chromosomes are pulled apart by shortening kinetochore microtubules and move toward the respective centrosomes to which they are attached.
Next, the nonkinetochore microtubules elongate, pushing the centrosomes (and the set of chromosomes to which they are attached) apart to opposite ends of the cell.
These two stages are sometimes called early and late anaphase. Early anaphase is usually defined as the separation of the sister chromatids, while late anaphase is the elongation of the microtubules and the microtubules being pulled farther apart. At the end of anaphase, the cell has succeeded in separating identical copies of the genetic material into two distinct populations.
## Telophase
Telophase (from the Greek τελος meaning "end") is a reversal of prophase and prometaphase events. It "cleans up" the after effects of mitosis. At telophase, the nonkinetochore microtubules continue to lengthen, elongating the cell even more. Corresponding sister chromosomes attach at opposite ends of the cell. A new nuclear envelope, using fragments of the parent cell's nuclear membrane, forms around each set of separated sister chromosomes. Both sets of chromosomes, now surrounded by new nuclei, unfold back into chromatin. Mitosis is complete, but cell division is not yet complete.
## Cytokinesis
Cytokinesis is often mistakenly thought to be the final part of telophase, however cytokinesis is a separate process that begins at the same time as telophase. Cytokinesis is technically not even a phase of mitosis, but rather a separate process, necessary for completing cell division. In animal cells, a cleavage furrow (pinch) containing a contractile ring develops where the metaphase plate used to be, pinching off the separated nuclei.[14] In both animal and plant cells, cell division is also driven by vesicles derived from the Golgi apparatus, which move along microtubules to the middle of the cell. [15] In plants this structure coalesces into a cell plate at the center of the phragmoplast and develops into a cell wall, separating the two nuclei. The phragmoplast is a microtubule structure typical for higher plants, whereas some green algae use a phycoplast microtubule array during cytokinesis.[16] Each daughter cell has a complete copy of the genome of its parent cell. The end of cytokinesis marks the end of the M-phase.
# Significance
The importance of mitosis is the maintenance of the chromosomal set; each cell formed receives chromosomes that are alike in composition and equal in number to the chromosomes of the parent cell. Transcription is generally believed to cease during mitosis, but epigenetic mechanisms such as bookmarking function during this stage of the cell cycle to ensure that the "memory" of which genes were active prior to entry into mitosis are transmitted to the daughter cells.[17]
# Consequences of errors
Although errors in mitosis are rare, the process may go wrong, especially during early cellular divisions in the zygote. Mitotic errors can be especially dangerous to the organism because future offspring from this parent cell will carry the same disorder.
In non-disjunction, a chromosome may fail to separate during anaphase. One daughter cell will receive both sister chromosomes and the other will receive none. This results in the former cell having three chromosomes coding for the same thing (two sisters and a homologue), a condition known as trisomy, and the latter cell having only one chromosome (the homologous chromosome), a condition known as monosomy. These cells are considered aneuploidic cells and these abnormal cells can cause cancer.[18]
Mitosis is a traumatic process. The cell goes through dramatic changes in ultrastructure, its organelles disintegrate and reform in a matter of hours, and chromosomes are jostled constantly by probing microtubules. Occasionally, chromosomes may become damaged. An arm of the chromosome may be broken and the fragment lost, causing deletion. The fragment may incorrectly reattach to another, non-homologous chromosome, causing translocation. It may reattach to the original chromosome, but in reverse orientation, causing inversion. Or, it may be treated erroneously as a separate chromosome, causing chromosomal duplication. The effect of these genetic abnormalities depend on the specific nature of the error. It may range from no noticeable effect, cancer induction, or organism death.
# Endomitosis
Endomitosis is a variant of mitosis without nuclear or cellular division, resulting in cells with many copies of the same chromosome occupying a single nucleus. This process may also be referred to as endoreduplication and the cells as endoploid.[2] An example of endomitosis would be what occurs in megakaryocytes to generate platelets within its cytoplasm.[19]
# Timeline in pictures
Real mitotic cells can be visualized through the microscope by staining them with fluorescent antibodies and dyes. These light micrographs are included below.
- Early prometaphase: The nuclear membrane has just degraded, allowing the microtubules to quickly interact with the kinetochores on the chromosomes, which have just condensed.
- Late metaphase: The centrosomes have moved to the poles of the cell and have established the mitotic spindle. The chromosomes, in light blue, have all assembled at the metaphase plate, except for one.
Late metaphase: The centrosomes have moved to the poles of the cell and have established the mitotic spindle. The chromosomes, in light blue, have all assembled at the metaphase plate, except for one.
- Anaphase: Lengthening nonkinetochore microtubules push the two sets of chromosomes further apart. | https://www.wikidoc.org/index.php/Endomitosis | |
8b28475d013059994ee8b0d348e59ec3a73a9b5d | wikidoc | Pinworm | Pinworm
# Overview
The pinworm (genus Enterobius), also known as threadworm (in the United Kingdom and Australia) or seatworm, is a parasitic worm. It is a nematode (roundworm) and a common intestinal parasite or helminth, especially in humans. The medical condition associated with pinworm infestation is known as enterobiasis (a type of helminthiasis) or less precisely as oxyuriasis in reference to the family Oxyuridae.
Throughout this article, the word "pinworm" refers to Enterobius. In British usage, however, pinworm refers to Strongyloides, while Enterobius is called threadworm.
# Classification
The pinworm (genus Enterobius) is a type of roundworm (nematode), and three species of pinworm have been identified with certainty. Humans are hosts only to Enterobius vermicularis (formerly Oxyurias vermicularis). Chimpanzees are host to Enterobius anthropopitheci, which is morphologically distinguishable from the human pinworm. Hugot (1983) claims there is another species affecting humans, Enterobius gregorii, which is supposedly a sister species of E. vermicularis, and has a slightly smaller spicule (i.e., sexual organ). Its existence is controversial however; Totkova et al. (2003) consider there to be insufficient evidence, and Hasegawa et al. (2006) contend that E. gregorii is a younger stage of E. vermicularis. Regardless of its status as a distinct species, E. gregorii is considered clinically identical to E. vermicularis.
# Morphology
The adult female has a sharply pointed posterior end, is 8 to 13 mm long, and 0.5 mm thick. The adult male is considerably smaller, measuring 2 to 5 mm long and 0.2 mm thick, and has a curved posterior end. The eggs are translucent and have a surface that adheres to objects. The eggs measure 50 to 60 μm by 20 to 30 μm, and have a thick shell flattened on one side. The small size and colourlessness of the eggs make them invisible to the naked eye, except in barely visible clumps of thousands of eggs. Eggs may contain a developing embryo or a fully developed pinworm larva. The larvae grow to 140–150 μm in length.
# Distribution
The pinworm has a worldwide distribution, and is the most common helminth (i.e., parasitic worm) infection in the United States, western Europe, and Oceania. In the United States, a study by the Center of Disease Control reported an overall incidence rate of 11.4% among people of all ages. Pinworms are particularly common in children, with prevalence rates in this age group having been reported as high as 61% in India, 50% in England, 39% in Thailand, 37% in Sweden, and 29% in Denmark. Finger sucking has been shown to increase both incidence and relapse rates, and nail biting has been similarly associated. Because it spreads from host to host through contamination, pinworms are common among people living in close contact, and tends to occur in all people within a household. The prevalence of pinworms is not associated with gender, nor with any particular social class, race, or culture. Pinworms are an exception to the tenet that intestinal parasites are uncommon in affluent communities. The earliest known instance of the pinworms associated with humans is evidenced by pinworm eggs found in coprolite, carbon dated to 7837 BC at western Utah; however 240 million years ago parasitic pinworm nematodes already infested pre-mammalian cynodonts: a fossilized egg was detected in fossil dung.
# Lifecycle
The entire lifecycle, from egg to adult, takes place in the human gastrointestinal tract of a single human host, from about 2–4 weeks or about 4–8 weeks.
The lifecycle begins with eggs being ingested. The eggs hatch in the duodenum (i.e., first part of the small intestine). The emerging pinworm larvae grow rapidly to a size of 140 to 150 μm, and migrate through the small intestine towards the colon. During this migration, they moult twice and become adults. Females survive for 5 to 13 weeks, and males about 7 weeks. The male and female pinworms mate in the ileum (i.e., last part of the small intestine), whereafter the male pinworms usually die, and are passed out with stool. The gravid female pinworms settle in the ileum, caecum (i.e., beginning of the large intestine), appendix and ascending colon, where they attach themselves to the mucosa and ingest colonic contents.
Almost the entire body of a gravid female becomes filled with eggs. The estimations of the number of eggs in a gravid female pinworm range from about 11,000 to 16,000. The egg-laying process begins about five weeks after initial ingestion of pinworm eggs by the human host. The gravid female pinworms migrate through the colon towards the rectum at a rate of 12 to 14 cm per hour. They emerge from the anus, and while moving on the skin near the anus, the female pinworms deposit eggs either through (1) contracting and expelling the eggs, (2) dying and then disintegrating, or (3) bodily rupture due to the host scratching the worm. After depositing the eggs, the female becomes opaque and dies. The reason the female emerges from the anus is to obtain the oxygen necessary for the maturation of the eggs.
# Infection
E. vermicularis causes the medical condition enterobiasis, whose primary symptom is itching in the anal area. Albendazole or mebendazole is the first-line treatment of pinworm infection. Pyrantel pamoate is alternative.
## Transmission
Pinworms spread through human-to-human transmission, by ingesting (i.e., swallowing) infectious pinworm eggs and/or by anal insertion. The eggs are hardy and can remain viable (i.e., infectious) in a moist environment up to three weeks. They do not tolerate heat well, but can survive in low temperatures: two-thirds of the eggs are still viable after 18 hours at −8 °C (18 °F).
After the eggs have been initially deposited near the anus, they are readily transmitted to other surfaces through contamination. The surface of the eggs is sticky when laid, and the eggs are readily transmitted from their initial deposit near the anus to fingernails, hands, night-clothing and bed linen. From here, eggs are further transmitted to food, water, furniture, toys, bathroom fixtures and other objects. Household pets often carry the eggs in their fur, while not actually being infected. Dust containing eggs can become airborne and widely dispersed when dislodged from surfaces, for instance when shaking out bed clothes and linen. Consequently, the eggs can enter the mouth and nose through inhalation, and be swallowed later. Although pinworms do not strictly multiply inside the body of their human host, some of the pinworm larvae may hatch on the anal mucosa, and migrate up the bowel and back into the gastrointestinal tract of the original host in a process called retroinfection. When this retroinfection occurs, it can lead to a heavy parasitic load and ensures the pinworm infestation continues or can be not clinically significant. Despite the limited, 13-week lifespan of individual pinworms, autoinfection (i.e., infection from the original host to itself), either through the anus-to-mouth route or through retroinfection, usually necessitates repeated treatment, at 2-week intervals, in order to remove the infection completely.
# Gallery
- Pinworms are sometimes diagnosed incidentally by pathology. Micrograph of pinworms in the appendix, H&E stain
- High magnification micrograph of a pinworm in cross section in the appendix, H&E stain
- Egg under a light microscope
- Pinworms are sometimes diagnosed incidentally by pathology: Micrograph of male pinworm in cross section, alae (blue arrow), intestine (red arrow) and testis (black arrow), H&E stain
- Pinworm eggs are easily seen under a microscope.
- This micrograph reveals the cephalic alae in the head region of E. vermicularis.
This micrograph reveals the cephalic alae in the head region of E. vermicularis.
- This image reveals some of the cytoarchitectural features seen in a lymph node specimen that had been extracted from a patient suspected of a Hantavirus illness. From Public Health Image Library (PHIL).
- Photomicrograph reveals some of the ultrastructural details of an Enterobius vermicularis egg, otherwise known as the human pinworm. From Public Health Image Library (PHIL). | Pinworm
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
The pinworm (genus Enterobius), also known as threadworm (in the United Kingdom and Australia) or seatworm, is a parasitic worm. It is a nematode (roundworm) and a common intestinal parasite or helminth, especially in humans.[5] The medical condition associated with pinworm infestation is known as enterobiasis[6] (a type of helminthiasis) or less precisely as oxyuriasis in reference to the family Oxyuridae.[7]
Throughout this article, the word "pinworm" refers to Enterobius. In British usage, however, pinworm refers to Strongyloides, while Enterobius is called threadworm.[8]
# Classification
The pinworm (genus Enterobius) is a type of roundworm (nematode), and three species of pinworm have been identified with certainty.[9] Humans are hosts only to Enterobius vermicularis (formerly Oxyurias vermicularis).[10] Chimpanzees are host to Enterobius anthropopitheci, which is morphologically distinguishable from the human pinworm.[3] Hugot (1983) claims there is another species affecting humans, Enterobius gregorii, which is supposedly a sister species of E. vermicularis, and has a slightly smaller spicule (i.e., sexual organ).[11] Its existence is controversial however; Totkova et al. (2003) consider there to be insufficient evidence,[4] and Hasegawa et al. (2006) contend that E. gregorii is a younger stage of E. vermicularis.[2][3] Regardless of its status as a distinct species, E. gregorii is considered clinically identical to E. vermicularis.[10]
# Morphology
The adult female has a sharply pointed posterior end, is 8 to 13 mm long, and 0.5 mm thick.[12] The adult male is considerably smaller, measuring 2 to 5 mm long and 0.2 mm thick, and has a curved posterior end.[12] The eggs are translucent[12] and have a surface that adheres to objects.[13] The eggs measure 50 to 60 μm by 20 to 30 μm, and have a thick shell flattened on one side.[12] The small size and colourlessness of the eggs make them invisible to the naked eye, except in barely visible clumps of thousands of eggs. Eggs may contain a developing embryo or a fully developed pinworm larva.[12] The larvae grow to 140–150 μm in length.[13]
# Distribution
The pinworm has a worldwide distribution,[14] and is the most common helminth (i.e., parasitic worm) infection in the United States, western Europe, and Oceania.[15][16] In the United States, a study by the Center of Disease Control reported an overall incidence rate of 11.4% among people of all ages.[16] Pinworms are particularly common in children, with prevalence rates in this age group having been reported as high as 61% in India, 50% in England, 39% in Thailand, 37% in Sweden, and 29% in Denmark.[16] Finger sucking has been shown to increase both incidence and relapse rates,[16] and nail biting has been similarly associated.[17] Because it spreads from host to host through contamination, pinworms are common among people living in close contact, and tends to occur in all people within a household.[14] The prevalence of pinworms is not associated with gender,[14] nor with any particular social class, race, or culture.[16] Pinworms are an exception to the tenet that intestinal parasites are uncommon in affluent communities.[16] The earliest known instance of the pinworms associated with humans is evidenced by pinworm eggs found in coprolite, carbon dated to 7837 BC at western Utah;[13] however 240 million years ago parasitic pinworm nematodes already infested pre-mammalian cynodonts: a fossilized egg was detected in fossil dung.[18]
# Lifecycle
The entire lifecycle, from egg to adult, takes place in the human gastrointestinal tract of a single human host,[12][13] from about 2–4 weeks[19] or about 4–8 weeks.[16]
The lifecycle begins with eggs being ingested.[13] The eggs hatch in the duodenum (i.e., first part of the small intestine).[20] The emerging pinworm larvae grow rapidly to a size of 140 to 150 μm,[19] and migrate through the small intestine towards the colon.[13] During this migration, they moult twice and become adults.[13][16] Females survive for 5 to 13 weeks, and males about 7 weeks.[13] The male and female pinworms mate in the ileum (i.e., last part of the small intestine),[13] whereafter the male pinworms usually die,[20] and are passed out with stool.[21] The gravid female pinworms settle in the ileum, caecum (i.e., beginning of the large intestine), appendix and ascending colon,[13] where they attach themselves to the mucosa[16] and ingest colonic contents.[14]
Almost the entire body of a gravid female becomes filled with eggs.[20] The estimations of the number of eggs in a gravid female pinworm range from about 11,000[13] to 16,000.[16] The egg-laying process begins about five weeks after initial ingestion of pinworm eggs by the human host.[13] The gravid female pinworms migrate through the colon towards the rectum at a rate of 12 to 14 cm per hour.[13] They emerge from the anus, and while moving on the skin near the anus, the female pinworms deposit eggs either through (1) contracting and expelling the eggs, (2) dying and then disintegrating, or (3) bodily rupture due to the host scratching the worm.[20] After depositing the eggs, the female becomes opaque and dies.[21] The reason the female emerges from the anus is to obtain the oxygen necessary for the maturation of the eggs.[21]
# Infection
E. vermicularis causes the medical condition enterobiasis, whose primary symptom is itching in the anal area.[22] Albendazole or mebendazole is the first-line treatment of pinworm infection. Pyrantel pamoate is alternative.
## Transmission
Pinworms spread through human-to-human transmission, by ingesting (i.e., swallowing) infectious pinworm eggs and/or by anal insertion.[16][20] The eggs are hardy and can remain viable (i.e., infectious) in a moist environment up to three weeks.[16][21] They do not tolerate heat well, but can survive in low temperatures: two-thirds of the eggs are still viable after 18 hours at −8 °C (18 °F).[21]
After the eggs have been initially deposited near the anus, they are readily transmitted to other surfaces through contamination.[20] The surface of the eggs is sticky when laid,[13][21] and the eggs are readily transmitted from their initial deposit near the anus to fingernails, hands, night-clothing and bed linen.[19] From here, eggs are further transmitted to food, water, furniture, toys, bathroom fixtures and other objects.[13][16][20] Household pets often carry the eggs in their fur, while not actually being infected.[23] Dust containing eggs can become airborne and widely dispersed when dislodged from surfaces, for instance when shaking out bed clothes and linen.[16][21][23] Consequently, the eggs can enter the mouth and nose through inhalation, and be swallowed later.[16][19][20][21] Although pinworms do not strictly multiply inside the body of their human host,[19] some of the pinworm larvae may hatch on the anal mucosa, and migrate up the bowel and back into the gastrointestinal tract of the original host[16][19] in a process called retroinfection.[16][21] When this retroinfection occurs, it can lead to a heavy parasitic load and ensures the pinworm infestation continues[16] or can be not clinically significant.[21] Despite the limited, 13-week lifespan of individual pinworms,[13] autoinfection (i.e., infection from the original host to itself), either through the anus-to-mouth route or through retroinfection, usually necessitates repeated treatment, at 2-week intervals, in order to remove the infection completely.[24]
# Gallery
- Pinworms are sometimes diagnosed incidentally by pathology. Micrograph of pinworms in the appendix, H&E stain
- High magnification micrograph of a pinworm in cross section in the appendix, H&E stain
- Egg under a light microscope
- Pinworms are sometimes diagnosed incidentally by pathology: Micrograph of male pinworm in cross section, alae (blue arrow), intestine (red arrow) and testis (black arrow), H&E stain
- Pinworm eggs are easily seen under a microscope.
- This micrograph reveals the cephalic alae in the head region of E. vermicularis.
This micrograph reveals the cephalic alae in the head region of E. vermicularis.
- This image reveals some of the cytoarchitectural features seen in a lymph node specimen that had been extracted from a patient suspected of a Hantavirus illness. From Public Health Image Library (PHIL). [25]
- Photomicrograph reveals some of the ultrastructural details of an Enterobius vermicularis egg, otherwise known as the human pinworm. From Public Health Image Library (PHIL). [25] | https://www.wikidoc.org/index.php/Enterobiasis_causes | |
2e40639268d36ef804b2c563a3bf70074cc81690 | wikidoc | Entonox | Entonox
Entonox, referred to colloquially as gas and air, is an analgesic used to ease pain during labour, trauma and minor surgical procedures. Entonox is the trade name for a mixture of fifty percent nitrous oxide (N2O or laughing gas) and fifty percent oxygen (O2). Entonox is administered by inhalation from a cylinder at a pressure of 137 bar (in the UK) or from a pipeline supply.
Its analgesic effect is strong (equivalent to 5 to 10 mg of morphine) and characterised by rapid onset and offset (i.e. it is very fast-acting and wears off very quickly).
Nitrous oxide is itself active (does not require any changes in the body to become active), and so has an onset in roughly the lung-brain circulation time. This gives it a peak action 30s after the start of administration; Entonox should thus be used accordingly, e.g. use should begin 30s before a contraction becomes painful in labour. It is removed from the body unchanged via the lungs, and does not accumulate under normal conditions, explaining the rapid offset.
Entonox is self administered i.e. there is no requirement for an anaesthetist to be present to (amongst other things) control the mix of nitrous oxide and oxygen.
Nitrous oxide can act as an anaesthetic in high doses. Self-administration of Entonox remains safe because if enough is inhaled to start to induce anaesthesia, the patient becomes unable to hold the valve, and so will drop it and soon exhale the residual gas. The 50% oxygen in Entonox ensures the patient will have sufficient oxygen in their system for a short period of apnoea to be safe.
Nitrous oxide and oxygen will separate at low temperatures (<4 °C), which will permit administration of hypoxic mixtures. Thus it should never be given from a cold cylinder, and the cylinder should be inverted a few times to mix the gases before use.
Nitrous oxide is more soluble than oxygen and nitrogen, so will tend to diffuse into any air spaces within the body. This makes it dangerous to use in patients with pneumothorax or who have recently been scuba diving, and there are cautions over its use with any bowel obstruction.
Entonox is produced by the BOC Group, which also owns the trademark.
The ability to combine nitrous oxide and oxygen at high pressure while remaining in the gaseous form is due to the Poynting effect (after John Henry Poynting, an English physicist).
The Poynting effect involves the dissolution of gaseous O2 when bubbled through liquid N2O, with vaporisation of the liquid to form a gaseous O2/N2O mixture. | Entonox
Entonox, referred to colloquially as gas and air, is an analgesic used to ease pain during labour, trauma and minor surgical procedures. Entonox is the trade name for a mixture of fifty percent nitrous oxide (N2O or laughing gas) and fifty percent oxygen (O2). Entonox is administered by inhalation from a cylinder at a pressure of 137 bar (in the UK) or from a pipeline supply.
Its analgesic effect is strong (equivalent to 5 to 10 mg of morphine) and characterised by rapid onset and offset (i.e. it is very fast-acting and wears off very quickly).
Nitrous oxide is itself active (does not require any changes in the body to become active), and so has an onset in roughly the lung-brain circulation time. This gives it a peak action 30s after the start of administration; Entonox should thus be used accordingly, e.g. use should begin 30s before a contraction becomes painful in labour. It is removed from the body unchanged via the lungs, and does not accumulate under normal conditions, explaining the rapid offset.
Entonox is self administered i.e. there is no requirement for an anaesthetist to be present to (amongst other things) control the mix of nitrous oxide and oxygen.
Nitrous oxide can act as an anaesthetic in high doses. Self-administration of Entonox remains safe because if enough is inhaled to start to induce anaesthesia, the patient becomes unable to hold the valve, and so will drop it and soon exhale the residual gas. The 50% oxygen in Entonox ensures the patient will have sufficient oxygen in their system for a short period of apnoea to be safe.
Nitrous oxide and oxygen will separate at low temperatures (<4 °C), which will permit administration of hypoxic mixtures. Thus it should never be given from a cold cylinder, and the cylinder should be inverted a few times to mix the gases before use.
Nitrous oxide is more soluble than oxygen and nitrogen, so will tend to diffuse into any air spaces within the body. This makes it dangerous to use in patients with pneumothorax or who have recently been scuba diving, and there are cautions over its use with any bowel obstruction.
Entonox is produced by the BOC Group, which also owns the trademark.
The ability to combine nitrous oxide and oxygen at high pressure while remaining in the gaseous form is due to the Poynting effect (after John Henry Poynting, an English physicist).
The Poynting effect involves the dissolution of gaseous O2 when bubbled through liquid N2O, with vaporisation of the liquid to form a gaseous O2/N2O mixture.
# External links
- BabyCentre entry on Entonox
- Detailed medical analysis of the drug
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Entonox | |
0884c5583e2ba0efb8d0d76c6ca2c6d0ac1bc384 | wikidoc | Epazote | Epazote
Epazote, Wormseed, Jesuit's Tea, Mexican Tea, or Herba Sancti Mariæ (Chenopodium ambrosioides) is a herb native to Central America, South America, and southern Mexico. It is an annual or short-lived perennial plant, growing to 1.2 m tall, irregularly branched, with oblong-lanceolate leaves up to 12 cm long. The flowers are small and green, produced in a branched panicle at the apex of the stem.
As well as in its native areas, it is grown in warm temperate to subtropical areas of Europe and the United States (Missouri, New England, Eastern United States), sometimes becoming an invasive weed.
The name epazote comes from Nahuatl epazōtl (IPA: Template:IPA) via Spanish.
# Culinary uses
Epazote is used as a leaf vegetable and herb for its pungent flavor. Raw, it has a resinous, medicinal pungency, similar to the liquorice taste of anise, fennel, or even tarragon, but stronger. Epazote's fragrance is strong, but difficult to describe. It has been compared to citrus, petroleum, savory, mint and putty.
Although it is traditionally used with black beans for flavor and its antiflatulent properties, it is also sometimes used to flavor other traditional Mexican dishes as well: it can be used to season quesadillas and sopes (especially those containing huitlacoche), soups, mole de olla, tamales with cheese and chile, chilaquiles, eggs and potatoes and enchiladas.
# Medicinal uses
Epazote is used as a leaf vegetable and herb for its pungent flavor and its claimed ability to prevent flatulence caused by eating beans but also in the treatment of amenorrhea, dysmenorrhea, malaria, chorea, hysteria, catarrh, and asthma.
Oil of chenopodium is derived from this plant. It is anthelmintic, that is, it kills intestinal worms, and was once listed for this use in the US Pharmacopoeia. It is also cited as an antispasmodic and abortifacient - the first birth control pills were derived from research on epazote.
Epazote essential oil contains ascaridole (up to 70%), limonene, p-cymene, and smaller amounts of numerous other monoterpenes and monoterpene derivatives (α-pinene, myrcene, terpinene, thymol, camphor and trans-isocarveol). Ascaridol (1,4-peroxido-p-menth-2-ene) is rather an uncommon constituent of spices; another plant owing much of its character to this monoterpene peroxide is boldo. Ascaridole is toxic and has a pungent, not very pleasant flavor; in pure form, it is an explosive sensitive to shock. Allegedly, ascaridole content is lower in epazote from México than in epazote grown in Europe or Asia. | Epazote
Epazote, Wormseed, Jesuit's Tea, Mexican Tea, or Herba Sancti Mariæ (Chenopodium ambrosioides) is a herb native to Central America, South America, and southern Mexico. It is an annual or short-lived perennial plant, growing to 1.2 m tall, irregularly branched, with oblong-lanceolate leaves up to 12 cm long. The flowers are small and green, produced in a branched panicle at the apex of the stem.
As well as in its native areas, it is grown in warm temperate to subtropical areas of Europe and the United States (Missouri, New England, Eastern United States)[1], sometimes becoming an invasive weed.
The name epazote comes from Nahuatl epazōtl (IPA: Template:IPA) via Spanish.
# Culinary uses
Epazote is used as a leaf vegetable and herb for its pungent flavor. Raw, it has a resinous, medicinal pungency, similar to the liquorice taste of anise, fennel, or even tarragon, but stronger. Epazote's fragrance is strong, but difficult to describe. It has been compared to citrus, petroleum, savory, mint and putty.
Although it is traditionally used with black beans for flavor and its antiflatulent properties, it is also sometimes used to flavor other traditional Mexican dishes as well: it can be used to season quesadillas and sopes (especially those containing huitlacoche), soups, mole de olla, tamales with cheese and chile, chilaquiles, eggs and potatoes and enchiladas.
# Medicinal uses
Epazote is used as a leaf vegetable and herb for its pungent flavor and its claimed ability to prevent flatulence caused by eating beans but also in the treatment of amenorrhea[2], dysmenorrhea, malaria, chorea, hysteria, catarrh, and asthma[3].
Oil of chenopodium is derived from this plant. It is anthelmintic, that is, it kills intestinal worms, and was once listed for this use in the US Pharmacopoeia. It is also cited as an antispasmodic and abortifacient - the first birth control pills were derived from research on epazote.
Epazote essential oil contains ascaridole (up to 70%), limonene, p-cymene, and smaller amounts of numerous other monoterpenes and monoterpene derivatives (α-pinene, myrcene, terpinene, thymol, camphor and trans-isocarveol). Ascaridol (1,4-peroxido-p-menth-2-ene) is rather an uncommon constituent of spices; another plant owing much of its character to this monoterpene peroxide is boldo. Ascaridole is toxic and has a pungent, not very pleasant flavor; in pure form, it is an explosive sensitive to shock. Allegedly, ascaridole content is lower in epazote from México than in epazote grown in Europe or Asia.
Template:Herbs & spices | https://www.wikidoc.org/index.php/Epazote | |
6bd56a79d206cd534046cbb0414607f0a2bcd578 | wikidoc | Ephedra | Ephedra
Ephedra is an alkaloid chemical compound traditionally obtained from the plant Ephedra sinica. E. sinica, known in Chinese as ma huang (麻黃; pinyin: má huáng), has been used in traditional Chinese medicine for 5,000 years for the treatment of asthma and hay fever, as well as for the common cold. Several additional species belonging to the genus Ephedra have traditionally been used for a variety of medicinal purposes, and are a possible candidate for the Soma plant of Indo-Iranian religion. Native Americans and Mormon pioneers drank a tea brewed from an Ephedra, called Mormon Tea.
In recent years, the safety of ephedra-containing dietary supplements has been questioned by the United States Food and Drug Administration (FDA), the National Center for Complementary and Alternative Medicine, and the medical community as a result of a high rate of serious side effects and ephedra-related deaths. In response to accumulating evidence of adverse effects and deaths related to ephedra, the FDA banned the sale of ephedra-containing supplements on April 12 2004. A suit by an ephedra manufacturer was upheld by a Federal District Court judge in Utah on April 14 2005. The FDA appealed this ruling, and on August 17 2006 the U.S. Court of Appeals for the Tenth Circuit upheld the FDA's ban of ephedra. As of June 2007, the sale of ephedra-containing dietary supplements remains illegal in the United States due to their health risks.
# Ephedra biochemistry
The alkaloids ephedrine and pseudoephedrine are the active constituents of the plant. Pseudoephedrine is used in over-the-counter decongestants. Derivatives of ephedrine are used to treat low blood pressure, but alternatives with reduced cardiovascular risk have replaced it for treating asthma. Ephedrine is also considered a performance-enhancing drug and is prohibited in most competitive sports. Some species in the Ephedra genus have no alkaloid content and are therefore essentially inert; however, the most commonly used species, E. sinica, has a total alkaloid content of 1–3% by dry weight. Ephedrine constitutes 40–90% of the alkaloid content, with the remainder consisting of pseudoephedrine and the demethylated forms of each compound.
# Effects and uses
Ephedra is both a stimulant and a thermogenic; its biological effects are due to its ephedrine and pseudoephedrine content. These compounds stimulate the brain, increase heart rate, constrict blood vessels (increasing blood pressure), and expand bronchial tubes (making breathing easier). Their thermogenic properties cause an increase in metabolism, evidenced by an increase in body heat.
In traditional Chinese herbology, E. sinica is included in many herbal formulas that treat cold and flu such as 麻黃湯 ma huang tang (ephedra decoction) or 麻杏石甘湯 ma xing shi gan tang (ephedra, apricot kernel, gypsum, and licorice decoction). Ephedra is used therapeutically as a diaphoretic to help expel exterior pathogens and regulate the proper functioning of the lungs.
Ephedra is widely used by athletes, despite a lack of evidence that it enhances athletic performance. Ephedra may also be used as a precursor in the illicit manufacture of methamphetamine.
Ephedra has also been used for weight loss, sometimes in combination with aspirin and caffeine. Some studies have shown that ephedra, when taken in a regulated and supervised environment, is effective for short-term weight loss, although it is unclear whether such weight loss is maintained. However, several reports have documented the large number of adverse events attributable to unregulated ephedra supplements.
Side effects of ephedra may include severe skin reactions, irritability, nervousness, dizziness, trembling, headache, insomnia, profuse perspiration, dehydration, itchy scalp and skin, vomiting, hyperthermia, irregular heartbeat, seizures, heart attack, stroke, or death.
# Purity and dosage
There are no formal requirements for standardization or quality control of dietary supplements in the United States, and the dosage of effective ingredients in supplements may vary widely from brand to brand or batch to batch. Studies of ephedra supplements have found significant discrepancies between the labeled dose and the actual amount of ephedra in the product. Significant variation in ephedrine alkaloid levels, by as much as 10-fold, was seen even from lot to lot within the same brand.
# Safety and regulatory actions in the United States
Escalating concerns regarding the safety of ephedra supplements led the FDA to ban the sale of ephedra-containing supplements in the United States in 2004. This ban was challenged by supplement manufacturers and initially overturned, but ultimately upheld.
## Initial concerns and supplement industry response
In 1997, in response to mounting concern over serious side effects of ephedra, the FDA proposed a ruling that would ban the sale of products containing 8 mg or more of ephedrine alkaloids and require stricter labeling of low-dose ephedra supplements. The FDA also proposed that ephedra labels should be required to disclose the health risks of ephedra, such as heart attack, stroke, or death.
In response to the proposed ruling, the supplement industry created a public relations group (the Ephedra Education Council) to oppose the changes and commissioned a scientific review by a private consulting firm, which reported that ephedra was safe. The Ephedra Education Council also attempted to block publication of a study confirming wide discrepancies between the labeled potency of supplements and the actual amount of ephedra in the product.
During this time, Metabolife, makers of the best-selling brand of ephedra supplement, had received over 14,000 complaints of adverse events associated with its product; these reports were not provided to the FDA. Senators Orrin Hatch and Tom Harkin, authors of the Dietary Supplements Health and Education Act, questioned the scientific basis for the FDA's proposed labeling changes and suggested that the number of problems reported were insufficient to warrant regulatory action. At the time, Hatch's son was working for a firm hired to lobby Congress and the FDA on behalf of ephedra manufacturers.
In addition to the activities of the Ephedra Education Council, Metabolife spent more than $4 million between 1998 and 2000 lobbying against state regulation of ephedra in Texas. Business Week reported that efforts to regulate ephedra and other potentially harmful supplements had been "beaten down by deep-pocketed industry lobbying."
Ultimately, in 2000, the FDA withdrew the proposed labeling changes and restrictions.
## Additional evidence
A review of ephedra-related adverse reactions, published in the New England Journal of Medicine in 2000, found a number of cases of sudden cardiac death or severe disability resulting from ephedra use, many of which occurred in young adults using ephedra in the labeled dosages. Subsequently, in response to pressure from the consumer advocacy group Public Citizen, Metabolife was compelled by the Department of Justice in 2002 to turn over reports of over 15,000 ephedra-related adverse events, ranging from insomnia to death, which the company had previously withheld from the FDA. Use of ephedra was considered to have possibly contributed to the death of Minnesota Vikings offensive lineman Korey Stringer from heatstroke in 2001.
## Death of Steve Bechler
Steve Bechler, a pitcher for the Baltimore Orioles, died of complications from heatstroke following a spring training workout on February 17 2003. The medical examiner found that ephedra toxicity played a "significant role" in Bechler's sudden death. Following Bechler's death, the FDA re-opened its efforts to regulate ephedra use. According to Bruce Silverglade, legal director for the Center for Science in the Public Interest, "All of a sudden Congress dropped objections to an ephedra ban and started demanding the FDA act."
Senator Orrin Hatch, who in 1999 had helped block the FDA's attempts to regulate ephedra, said in March 2003 that "...it has been obvious to even the most casual observer that problems exist," and called FDA action to regulate ephedra "long overdue." Given Hatch's prior defense of ephedra, Time magazine described his statement as "a dazzling display of hypocrisy."
## Ephedra banned
In response to renewed calls for the regulation of ephedra, the FDA commissioned a large meta-analysis of ephedra's safety and efficacy by the RAND Corporation. This study found that while ephedra promoted modest short-term weight loss, there was no evidence that it was effective for long-term weight loss or performance enhancement. The use of ephedra in this study was associated with significant gastrointestinal, psychiatric, and autonomic side effects. Almost simultaneously, a study in Annals of Internal Medicine found that ephedra was 100 to 700 times more likely to cause a significant adverse reaction compared to other commonly used supplements such as kava or Ginkgo biloba.
On December 30 2003, the FDA issued a press release recommending that consumers stop buying and using ephedra, and indicating its intention to ban the sale of ephedra-containing supplements. Subsequently, on April 12 2004, the FDA issued a final rule banning the sale of ephedra-containing dietary supplements. Tommy Thompson, the Secretary of Health and Human Services, stated that "...These products pose unacceptable health risks, and any consumers who are still using them should stop immediately."
## Legal challenges
Nutraceutical Corporation, a supplement manufacturer based in Park City, Utah, challenged the legality of the FDA's ban of ephedra as exceeding the authority given the agency by the Dietary Health Supplements and Education Act. Nutraceutical Corporation stated that they did not intend to start marketing ephedra, but were concerned about the scope of the FDA's regulatory action. Judge Tena Campbell of the Utah Federal District Court ruled that the FDA had not proven that low doses of ephedra were unsafe, although she also noted that studies to address the safety of low-dose ephedra would be unethical. Nevertheless, her ruling overturned the ban on the sale of ephedra in the state of Utah, and called into question whether the ban could be enforced anywhere in the United States.
The ruling was appealed to the U.S. Court of Appeals for the Tenth Circuit in Denver, Colorado. On August 17 2006, the Appeals Court upheld the FDA's ban of ephedra, finding that the 133,000-page administrative record compiled by the FDA supported the agency's finding that ephedra posed an unreasonable risk to consumers. Nutraceutical Corp. filed a petition for a writ of certiorari seeking a rehearing on the ban of ephedra; however, on May 14 2007 the United States Supreme Court declined to hear this petition. The sale of ephedra-containing dietary supplements remains illegal in the United States due to their health risks.
# Use in sports
Ephedrine is listed as a banned substance by both the International Olympic Committee and the World Anti-Doping Agency. The U.S. National Football League banned players from using ephedra as a dietary supplement in 2001 after the death of Minnesota Vikings offensive tackle Korey Stringer; ephedra was found in Stringer's locker and was believed to have contributed to his death. The substance is also banned by the National Basketball Association. Nonetheless, ephedra remains widely used by athletes; a 2006 survey of collegiate hockey players found that nearly half had used ephedra in the belief it would enhance athletic performance.
## Prominent cases of ephedra use
In the 1994 FIFA World Cup, the Argentine footballer Diego Armando Maradona tested positive for ephedrine. The Japanese motorcycle racer Noriyuki Haga tested positive for it in 2000, being disqualified from two races and banned from two more as a result. NFL punter Todd Sauerbrun of the Denver Broncos was suspended for the first month of the 2006 season after testing positive for ephedra. | Ephedra
Template:Otheruses4
Template:Globalize
Ephedra is an alkaloid chemical compound traditionally obtained from the plant Ephedra sinica.[1] E. sinica, known in Chinese as ma huang (麻黃; pinyin: má huáng), has been used in traditional Chinese medicine for 5,000 years for the treatment of asthma and hay fever, as well as for the common cold.[2] Several additional species belonging to the genus Ephedra have traditionally been used for a variety of medicinal purposes, and are a possible candidate for the Soma plant of Indo-Iranian religion.[3] Native Americans and Mormon pioneers drank a tea brewed from an Ephedra, called Mormon Tea.
In recent years, the safety of ephedra-containing dietary supplements has been questioned by the United States Food and Drug Administration (FDA), the National Center for Complementary and Alternative Medicine, and the medical community as a result of a high rate of serious side effects and ephedra-related deaths.[4][5][6][7][8] In response to accumulating evidence of adverse effects and deaths related to ephedra, the FDA banned the sale of ephedra-containing supplements on April 12 2004.[9] A suit by an ephedra manufacturer was upheld by a Federal District Court judge in Utah on April 14 2005. [10] The FDA appealed this ruling, and on August 17 2006 the U.S. Court of Appeals for the Tenth Circuit upheld the FDA's ban of ephedra.[11] As of June 2007, the sale of ephedra-containing dietary supplements remains illegal in the United States due to their health risks.
# Ephedra biochemistry
The alkaloids ephedrine and pseudoephedrine are the active constituents of the plant. Pseudoephedrine is used in over-the-counter decongestants. Derivatives of ephedrine are used to treat low blood pressure, but alternatives with reduced cardiovascular risk have replaced it for treating asthma. Ephedrine is also considered a performance-enhancing drug and is prohibited in most competitive sports. Some species in the Ephedra genus have no alkaloid content and are therefore essentially inert; however, the most commonly used species, E. sinica, has a total alkaloid content of 1–3% by dry weight. Ephedrine constitutes 40–90% of the alkaloid content, with the remainder consisting of pseudoephedrine and the demethylated forms of each compound.[12]
# Effects and uses
Ephedra is both a stimulant and a thermogenic; its biological effects are due to its ephedrine and pseudoephedrine content.[13] These compounds stimulate the brain, increase heart rate, constrict blood vessels (increasing blood pressure), and expand bronchial tubes (making breathing easier). Their thermogenic properties cause an increase in metabolism, evidenced by an increase in body heat.
In traditional Chinese herbology, E. sinica is included in many herbal formulas that treat cold and flu such as 麻黃湯 ma huang tang (ephedra decoction) or 麻杏石甘湯 ma xing shi gan tang (ephedra, apricot kernel, gypsum, and licorice decoction). Ephedra is used therapeutically as a diaphoretic to help expel exterior pathogens and regulate the proper functioning of the lungs.[14]
Ephedra is widely used by athletes,[15] despite a lack of evidence that it enhances athletic performance.[16][17] Ephedra may also be used as a precursor in the illicit manufacture of methamphetamine.[18]
Ephedra has also been used for weight loss, sometimes in combination with aspirin and caffeine. Some studies have shown that ephedra, when taken in a regulated and supervised environment, is effective for short-term weight loss, although it is unclear whether such weight loss is maintained.[19] However, several reports have documented the large number of adverse events attributable to unregulated ephedra supplements.[20]
Side effects of ephedra may include severe skin reactions, irritability, nervousness, dizziness, trembling, headache, insomnia, profuse perspiration, dehydration, itchy scalp and skin, vomiting, hyperthermia, irregular heartbeat, seizures, heart attack, stroke, or death.[21]
# Purity and dosage
There are no formal requirements for standardization or quality control of dietary supplements in the United States, and the dosage of effective ingredients in supplements may vary widely from brand to brand or batch to batch.[22][23][24] Studies of ephedra supplements have found significant discrepancies between the labeled dose and the actual amount of ephedra in the product. Significant variation in ephedrine alkaloid levels, by as much as 10-fold, was seen even from lot to lot within the same brand.[25][26]
# Safety and regulatory actions in the United States
Escalating concerns regarding the safety of ephedra supplements led the FDA to ban the sale of ephedra-containing supplements in the United States in 2004. This ban was challenged by supplement manufacturers and initially overturned, but ultimately upheld.
## Initial concerns and supplement industry response
In 1997, in response to mounting concern over serious side effects of ephedra, the FDA proposed a ruling that would ban the sale of products containing 8 mg or more of ephedrine alkaloids and require stricter labeling of low-dose ephedra supplements. The FDA also proposed that ephedra labels should be required to disclose the health risks of ephedra, such as heart attack, stroke, or death.[27]
In response to the proposed ruling, the supplement industry created a public relations group (the Ephedra Education Council) to oppose the changes and commissioned a scientific review by a private consulting firm, which reported that ephedra was safe.[28] The Ephedra Education Council also attempted to block publication of a study confirming wide discrepancies between the labeled potency of supplements and the actual amount of ephedra in the product.[22]
During this time, Metabolife, makers of the best-selling brand of ephedra supplement, had received over 14,000 complaints of adverse events associated with its product; these reports were not provided to the FDA.[28][29] Senators Orrin Hatch and Tom Harkin, authors of the Dietary Supplements Health and Education Act, questioned the scientific basis for the FDA's proposed labeling changes and suggested that the number of problems reported were insufficient to warrant regulatory action. At the time, Hatch's son was working for a firm hired to lobby Congress and the FDA on behalf of ephedra manufacturers.[30]
In addition to the activities of the Ephedra Education Council, Metabolife spent more than $4 million between 1998 and 2000 lobbying against state regulation of ephedra in Texas.[31] Business Week reported that efforts to regulate ephedra and other potentially harmful supplements had been "beaten down by deep-pocketed industry lobbying."[32]
Ultimately, in 2000, the FDA withdrew the proposed labeling changes and restrictions.[33]
## Additional evidence
A review of ephedra-related adverse reactions, published in the New England Journal of Medicine in 2000, found a number of cases of sudden cardiac death or severe disability resulting from ephedra use, many of which occurred in young adults using ephedra in the labeled dosages.[4] Subsequently, in response to pressure from the consumer advocacy group Public Citizen,[32] Metabolife was compelled by the Department of Justice in 2002 to turn over reports of over 15,000 ephedra-related adverse events, ranging from insomnia to death, which the company had previously withheld from the FDA.[34][28] Use of ephedra was considered to have possibly contributed to the death of Minnesota Vikings offensive lineman Korey Stringer from heatstroke in 2001.[35]
## Death of Steve Bechler
Steve Bechler, a pitcher for the Baltimore Orioles, died of complications from heatstroke following a spring training workout on February 17 2003. The medical examiner found that ephedra toxicity played a "significant role" in Bechler's sudden death.[36] Following Bechler's death, the FDA re-opened its efforts to regulate ephedra use. According to Bruce Silverglade, legal director for the Center for Science in the Public Interest, "All of a sudden [after Bechler's death] Congress dropped objections to an ephedra ban and started demanding the FDA act."[28]
Senator Orrin Hatch, who in 1999 had helped block the FDA's attempts to regulate ephedra, said in March 2003 that "...it has been obvious to even the most casual observer that problems exist," and called FDA action to regulate ephedra "long overdue."[30] Given Hatch's prior defense of ephedra, Time magazine described his statement as "a dazzling display of hypocrisy."[37]
## Ephedra banned
In response to renewed calls for the regulation of ephedra, the FDA commissioned a large meta-analysis of ephedra's safety and efficacy by the RAND Corporation. This study found that while ephedra promoted modest short-term weight loss, there was no evidence that it was effective for long-term weight loss or performance enhancement. The use of ephedra in this study was associated with significant gastrointestinal, psychiatric, and autonomic side effects.[38] Almost simultaneously, a study in Annals of Internal Medicine found that ephedra was 100 to 700 times more likely to cause a significant adverse reaction compared to other commonly used supplements such as kava or Ginkgo biloba.[5]
On December 30 2003, the FDA issued a press release recommending that consumers stop buying and using ephedra, and indicating its intention to ban the sale of ephedra-containing supplements.[39] Subsequently, on April 12 2004, the FDA issued a final rule banning the sale of ephedra-containing dietary supplements. Tommy Thompson, the Secretary of Health and Human Services, stated that "...These products pose unacceptable health risks, and any consumers who are still using them should stop immediately."[9]
## Legal challenges
Nutraceutical Corporation, a supplement manufacturer based in Park City, Utah, challenged the legality of the FDA's ban of ephedra as exceeding the authority given the agency by the Dietary Health Supplements and Education Act. Nutraceutical Corporation stated that they did not intend to start marketing ephedra, but were concerned about the scope of the FDA's regulatory action. Judge Tena Campbell of the Utah Federal District Court ruled that the FDA had not proven that low doses of ephedra were unsafe, although she also noted that studies to address the safety of low-dose ephedra would be unethical. Nevertheless, her ruling overturned the ban on the sale of ephedra in the state of Utah, and called into question whether the ban could be enforced anywhere in the United States.[40]
The ruling was appealed to the U.S. Court of Appeals for the Tenth Circuit in Denver, Colorado. On August 17 2006, the Appeals Court upheld the FDA's ban of ephedra, finding that the 133,000-page administrative record compiled by the FDA supported the agency's finding that ephedra posed an unreasonable risk to consumers.[11] Nutraceutical Corp. filed a petition for a writ of certiorari seeking a rehearing on the ban of ephedra; however, on May 14 2007 the United States Supreme Court declined to hear this petition. The sale of ephedra-containing dietary supplements remains illegal in the United States due to their health risks.[7]
# Use in sports
Ephedrine is listed as a banned substance by both the International Olympic Committee and the World Anti-Doping Agency.[41] The U.S. National Football League banned players from using ephedra as a dietary supplement in 2001 after the death of Minnesota Vikings offensive tackle Korey Stringer; ephedra was found in Stringer's locker and was believed to have contributed to his death.[35][42] The substance is also banned by the National Basketball Association.[40] Nonetheless, ephedra remains widely used by athletes; a 2006 survey of collegiate hockey players found that nearly half had used ephedra in the belief it would enhance athletic performance.[43]
## Prominent cases of ephedra use
In the 1994 FIFA World Cup, the Argentine footballer Diego Armando Maradona tested positive for ephedrine.[44] The Japanese motorcycle racer Noriyuki Haga tested positive for it in 2000, being disqualified from two races and banned from two more as a result.[45] NFL punter Todd Sauerbrun of the Denver Broncos was suspended for the first month of the 2006 season after testing positive for ephedra.[42] | https://www.wikidoc.org/index.php/Ephedra | |
eb9b330b8d6405bb75b159efdf71a41b569d3ddf | wikidoc | Epitope | Epitope
An epitope is the part of a macromolecule that is recognized by the immune system, specifically by antibodies, B cells, or T cells. Although epitopes are usually thought to be derived from nonself proteins, sequences derived from the host that can be recognized are also classified as epitopes.
Most epitopes recognized by antibodies or B cells can be thought of as three-dimensional surface features of an antigen molecule; these features fit precisely and thus bind to antibodies. The part of an antibody that recognizes the epitope is called a paratope. Exceptions are linear epitopes, which are determined by the amino acid sequence (the primary structure) rather than by the 3D shape (tertiary structure) of a protein.
T cell epitopes are presented on the surface of an antigen-presenting cell, where they are bound to MHC molecules. T cell epitopes presented by MHC class I molecules are typically peptides between 8 and 11 amino acids in lengths, whereas MHC class II molecules present longer peptides, and non-classical MHC molecules also present non-peptidic epitopes such as glycolipids.
Epitopes can be mapped using protein microarrays, and with the ELISPOT or ELISA techniques.
Genetic sequences coding for epitopes that are recognised by common antibodies can be fused to genes, thus aiding further molecular characterization of the gene product.
Common epitopes used for this purpose are c-myc, HA, FLAG, V5.
Epitopes are sometimes cross-reactive. This property is exploited by the immune system in regulation by anti-idiotypic antibodies (originally proposed by Nobel laureate Niels Kaj Jerne). If an antibody binds to an antigen's epitope, the paratope could become the epitope for another antibody that will then bind to it. If this second antibody is of IgM class, its binding can upregulate the immune response; if the second antibody is of IgG class, its binding can downregulate the immune response.
Intensive research is currently taking place to design reliable tools that will predict epitopes on proteins. | Epitope
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
An epitope is the part of a macromolecule that is recognized by the immune system, specifically by antibodies, B cells, or T cells. Although epitopes are usually thought to be derived from nonself proteins, sequences derived from the host that can be recognized are also classified as epitopes.
Most epitopes recognized by antibodies or B cells can be thought of as three-dimensional surface features of an antigen molecule; these features fit precisely and thus bind to antibodies. The part of an antibody that recognizes the epitope is called a paratope. Exceptions are linear epitopes, which are determined by the amino acid sequence (the primary structure) rather than by the 3D shape (tertiary structure) of a protein.
T cell epitopes are presented on the surface of an antigen-presenting cell, where they are bound to MHC molecules. T cell epitopes presented by MHC class I molecules are typically peptides between 8 and 11 amino acids in lengths, whereas MHC class II molecules present longer peptides, and non-classical MHC molecules also present non-peptidic epitopes such as glycolipids.
Epitopes can be mapped using protein microarrays, and with the ELISPOT or ELISA techniques.
Genetic sequences coding for epitopes that are recognised by common antibodies can be fused to genes, thus aiding further molecular characterization of the gene product.
Common epitopes used for this purpose are c-myc, HA, FLAG, V5.
Epitopes are sometimes cross-reactive. This property is exploited by the immune system in regulation by anti-idiotypic antibodies (originally proposed by Nobel laureate Niels Kaj Jerne). If an antibody binds to an antigen's epitope, the paratope could become the epitope for another antibody that will then bind to it. If this second antibody is of IgM class, its binding can upregulate the immune response; if the second antibody is of IgG class, its binding can downregulate the immune response.
Intensive research is currently taking place to design reliable tools that will predict epitopes on proteins. | https://www.wikidoc.org/index.php/Epitope | |
1c56e5d2e34cdff38742feda6a379d748555865e | wikidoc | Epoetin | Epoetin
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# Black Box Warning
# Overview
Epoetin is an erythropoiesis-stimulating agent (ESA) that is FDA approved for the treatment of anemia due to chronic kidney disease, anemia due to zidovudine in HIV-infected patients, anemia due to chemotherapy in patients with cancer, reduction of allogeneic red blood cell transfusions in patients undergoing elective, noncardiac, nonvascular surgery. There is a Black Box Warning for this drug as shown here. Common adverse reactions include edema, injection site irritation, injection site pain, pruritus, rash, nausea, vomiting, arthralgia, myalgia, dizziness, headache, insomnia, cough, upper respiratory infection, fever.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Evaluate the iron status in all patients before and during treatment and maintain iron repletion. Correct or exclude other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding, etc.) before initiating Epogen
- Epogen is indicated for the treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and not on dialysis to decrease the need for red blood cell (RBC) transfusion.
- In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL. No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks. Individualize dosing and use the lowest dose of Epogen sufficient to reduce the need for RBC transfusions. *Physicians and patients should weigh the possible benefits of decreasing transfusions against the increased risks of death and other serious cardiovascular adverse events.
- When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly. When adjusting therapy consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability. A single hemoglobin excursion may not require a dosing change.
- Do not increase the dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently. Avoid frequent dose adjustments.
- If the hemoglobin rises rapidly (e.g., more than 1 g/dL in any 2-week period), reduce the dose of Epogen by 25% or more as needed to reduce rapid responses.
- For patients who do not respond adequately, if the hemoglobin has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%.
- For patients who do not respond adequately over a 12-week escalation period, increasing the Epogen dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin level sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia. Discontinue Epogen if responsiveness does not improve.
- Initiate Epogen treatment when the hemoglobin level is less than 10 g/dL.
- If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of Epogen.
- The recommended starting dose for adult patients is 50 to 100 Units/kg 3 times weekly intravenously or subcutaneously. For pediatric patients, a starting dose of 50 Units/kg 3 times weekly intravenously or subcutaneously is recommended. The intravenous route is recommended for patients on hemodialysis.
- Consider initiating Epogen treatment only when the hemoglobin level is less than 10 g/dL and the following considerations apply:
- The rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion and,
- Reducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal
- If the hemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of Epogen, and use the lowest dose of Epogen sufficient to reduce the need for RBC transfusions.
- The recommended starting dose for adult patients is 50 to 100 Units/kg 3 times weekly intravenously or subcutaneously.
- Epogen is indicated for the treatment of anemia due to zidovudine administered at ≤ 4200 mg/week in HIV-infected patients with endogenous serum erythropoietin levels of ≤ 500 mUnits/mL.
- Starting Dose
- The recommended starting dose in adults is 100 Units/kg as an intravenous or subcutaneous injection 3 times per week.
- Dose Adjustment
- If hemoglobin does not increase after 8 weeks of therapy, increase Epogen dose by approximately
- 50 to 100 Units/kg at 4- to 8-week intervals until hemoglobin reaches a level needed to avoid RBC transfusions or 300 Units/kg.
- Withhold Epogen if hemoglobin exceeds 12 g/dL. Resume therapy at a dose 25% below the previous dose when hemoglobin declines to less than 11 g/dL.
- Discontinue Epogen if an increase in hemoglobin is not achieved at a dose of 300 Units/kg for 8 weeks.
- Epogen is indicated for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy.
- Initiate Epogen in patients on cancer chemotherapy only if the hemoglobin is less than 10 g/dL, and if there is a minimum of two additional months of planned chemotherapy.
- Use the lowest dose of Epogen necessary to avoid RBC transfusions.
- Recommended Starting Dose
- Adults:
- 150 Units/kg subcutaneously 3 times per week until completion of a chemotherapy course or
- 40,000 Units subcutaneously weekly until completion of a chemotherapy course.
- Dose Reduction
- Reduce dose by 25% if:
- Hemoglobin increases greater than 1 g/dL in any 2-week period or
- Hemoglobin reaches a level needed to avoid RBC transfusion.
- Withhold dose if hemoglobin exceeds a level needed to avoid RBC transfusion. Reinitiate at a dose 25% below the previous dose when hemoglobin approaches a level where RBC transfusions may be required.
- Dose Increase
- After the initial 4 weeks of Epogen therapy, if hemoglobin increases by less than 1 g/dL and remains below 10 g/dL, increase dose to:
- 300 Units/kg three times per week in adults or
- 60,000 Units weekly in adults
- 900 Units/kg (maximum 60,000 Units) weekly in children
- After 8 weeks of therapy, if there is no response as measured by hemoglobin levels or if RBC transfusions are still required, discontinue Epogen.
- Epogen is indicated to reduce the need for allogeneic RBC transfusions among patients with perioperative hemoglobin > 10 to ≤ 13 g/dL who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery. Epogen is not indicated for patients who are willing to donate autologous blood pre-operatively.
- 300 Units/kg per day subcutaneously for 15 days total: administered daily for 10 days before surgery, on the day of surgery, and for 4 days after surgery.
- 600 Units/kg subcutaneously in 4 doses administered 21, 14, and 7 days before surgery and on the day of surgery.
- Deep venous thrombosis prophylaxis is recommended during Epogen therapy.
- Do not shake. Do not use Epogen that has been shaken or frozen.
- Protect vials from light.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use any vials exhibiting particulate matter or discoloration.
- Discard unused portions of Epogen in preservative-free vials. Do not re-enter preservative-free vials.
- Store unused portions of Epogen in multidose vials at 36°F to 46° F (2°C to 8°C). Discard 21 days after initial entry.
- Do not dilute. Do not mix with other drug solutions except for admixing as described below:
- Preservative-free Epogen from single-use vials may be admixed in a syringe with bacteriostatic 0.9% sodium chloride injection, USP, with benzyl alcohol 0.9% (bacteriostatic saline) in a 1:1 ratio using aseptic technique at the time of administration. Risks are associated with benzyl alcohol in neonates, infants, pregnant women, and nursing mothers.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Epoetin in adult patients.
### Non–Guideline-Supported Use
- Subcutaneous erythropoietin (average dose: 5227 units/week) and intravenous (IV) iron (average dose: 185 milligrams (mg)/month).
- Epoetin alfa 200 units/kilogram/day for 5 consecutive days per week for up to 7 weeks during radiotherapy.
- Intravenous (IV) erythropoietin (EPO) 300 units/kilogram/day plus IV iron sucrose 200 milligrams (mg)/day on days 1 to 4 postpartum.
- Epoetin alfa (Procrit(R)) 40,000 units subcutaneously once weekly.
- Erythropoietin (150 units/kilogram 3 times/week initially with adjustments every 3 weeks as needed).
- Erythropoietin alfa 150 international units/kilogram subcutaneously 3 times weekly for 26 weeks.
- Subcutaneous erythropoietin 10,000 units 3 days per week.
- 100 units/kilogram (kg) 3 times per week for eight weeks.
- 150 international units/kilogram subcutaneously was administered 3 times per week for at least 12 weeks.
- Epoetin alfa doses of 12,000 to 24,000 units subcutaneously once weekly or 300 to 600 units/kilogram twice weekly.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- Epogen is indicated for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy
- Pediatric Patients (5 to 18 years):
- 600 Units/kg intravenously weekly until completion of a chemotherapy course.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Epoetin in pediatric patients.
### Non–Guideline-Supported Use
- IV erythropoietin dosing was 1250 units/kg/wk as 5 divided doses.
# Contraindications
- Uncontrolled hypertension.
- Pure red cell aplasia (PRCA) that begins after treatment with Epogen or other erythropoietin protein drugs.
- Serious allergic reactions to Epogen.
- Epogen from multidose vials contains benzyl alcohol and is contraindicated in:
- Neonates, infants, pregnant women, and nursing mothers. Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. When therapy with Epogen is needed in neonates and infants, use single-dose vials; do not admix with bacteriostatic saline containing benzyl alcohol.
# Warnings
### Precautions
- In controlled clinical trials of patients with CKD comparing higher hemoglobin targets (13 - 14 g/dL) to lower targets (9 - 11.3 g/dL), Epogen and other ESAs increased the risk of death, myocardial infarction, stroke, congestive heart failure, thrombosis of hemodialysis vascular access, and other thromboembolic events in the higher target groups.
- Using ESAs to target a hemoglobin level of greater than 11 g/dL increases the risk of serious adverse cardiovascular reactions and has not been shown to provide additional benefit. Use caution in patients with coexistent cardiovascular disease and stroke. Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality than other patients. A rate of hemoglobin rise of greater than 1 g/dL over 2 weeks may contribute to these risks.
- In controlled clinical trials of patients with cancer, Epogen and other ESAs increased the risks for death and serious adverse cardiovascular reactions. These adverse reactions included myocardial infarction and stroke.
- In controlled clinical trials, ESAs increased the risk of death in patients undergoing coronary artery bypass graft surgery (CABG) and the risk of deep venous thrombosis (DVT) in patients undergoing orthopedic procedures.
- The design and overall results of the 3 large trials comparing higher and lower hemoglobin targets are shown in Table 1.
- Patients with Chronic Kidney Disease
- Normal Hematocrit Study (NHS)
A prospective, randomized, open-label study of 1265 patients with chronic kidney disease on dialysis with documented evidence of congestive heart failure or ischemic heart disease was designed to test the hypothesis that a higher target hematocrit (Hct) would result in improved outcomes compared with a lower target Hct. In this study, patients were randomized to epoetin alfa treatment targeted to a maintenance hemoglobin of either 14 ± 1 g/dL or 10 ± 1 g/dL. The trial was terminated early with adverse safety findings of higher mortality in the high hematocrit target group. Higher mortality (35% vs. 29%) was observed for the patients randomized to a target hemoglobin of 14 g/dL than for the patients randomized to a target hemoglobin of 10 g/dL. For all-cause mortality, the HR=1.27; 95% CI (1.04, 1.54); p=0.018. The incidence of nonfatal myocardial infarction, vascular access thrombosis, and other thrombotic events was also higher in the group randomized to a target hemoglobin of 14 g/dL.
- A prospective, randomized, open-label study of 1265 patients with chronic kidney disease on dialysis with documented evidence of congestive heart failure or ischemic heart disease was designed to test the hypothesis that a higher target hematocrit (Hct) would result in improved outcomes compared with a lower target Hct. In this study, patients were randomized to epoetin alfa treatment targeted to a maintenance hemoglobin of either 14 ± 1 g/dL or 10 ± 1 g/dL. The trial was terminated early with adverse safety findings of higher mortality in the high hematocrit target group. Higher mortality (35% vs. 29%) was observed for the patients randomized to a target hemoglobin of 14 g/dL than for the patients randomized to a target hemoglobin of 10 g/dL. For all-cause mortality, the HR=1.27; 95% CI (1.04, 1.54); p=0.018. The incidence of nonfatal myocardial infarction, vascular access thrombosis, and other thrombotic events was also higher in the group randomized to a target hemoglobin of 14 g/dL.
- CHOIR
A randomized, prospective trial, 1432 patients with anemia due to CKD who were not undergoing dialysis and who had not previously received epoetin alfa therapy were randomized to epoetin alfa treatment targeting a maintenance hemoglobin concentration of either 13.5 g/dL or 11.3 g/dL. The trial was terminated early with adverse safety findings. A major cardiovascular event (death, myocardial infarction, stroke, or hospitalization for congestive heart failure) occurred in 125 of the 715 patients (18%) in the higher hemoglobin group compared to 97 of the 717 patients (14%) in the lower hemoglobin group .
- A randomized, prospective trial, 1432 patients with anemia due to CKD who were not undergoing dialysis and who had not previously received epoetin alfa therapy were randomized to epoetin alfa treatment targeting a maintenance hemoglobin concentration of either 13.5 g/dL or 11.3 g/dL. The trial was terminated early with adverse safety findings. A major cardiovascular event (death, myocardial infarction, stroke, or hospitalization for congestive heart failure) occurred in 125 of the 715 patients (18%) in the higher hemoglobin group compared to 97 of the 717 patients (14%) in the lower hemoglobin group .
- TREAT
A randomized, double-blind, placebo-controlled, prospective trial of 4038 patients with: CKD not on dialysis (eGFR of 20 – 60 mL/min), anemia (hemoglobin levels ≤ 11 g/dL), and type 2 diabetes mellitus, patients were randomized to receive either darbepoetin alfa treatment or a matching placebo. Placebo group patients also received darbepoetin alfa when their hemoglobin levels were below 9 g/dL. The trial objectives were to demonstrate the benefit of darbepoetin alfa treatment of the anemia to a target hemoglobin level of 13 g/dL, when compared to a "placebo" group, by reducing the occurrence of either of two primary endpoints: (1) a composite cardiovascular endpoint of all-cause mortality or a specified cardiovascular event (myocardial ischemia, CHF,MI, and CVA) or (2) a composite renal endpoint of all-cause mortality or progression to end stage renal disease. The overall risks for each of the two primary endpoints (the cardiovascular composite and the renal composite) were not reduced with darbepoetin alfa treatment (see Table 1), but the risk of stroke was increased nearly two-fold in the darbepoetin alfa -treated group versus the placebo group: annualized stroke rate 2.1% vs. 1.1%, respectively, HR 1.92; 95% CI: 1.38, 2.68; p < 0.001. The relative risk of stroke was particularly high in patients with a prior stroke: annualized stroke rate 5.2% in the darbepoetin alfa- treated group and 1.9% in the placebo group, HR 3.07; 95% CI: 1.44, 6.54. Also, among darbepoetin alfa -treated subjects with a past history of cancer, there were more deaths due to all causes and more deaths adjudicated as due to cancer, in comparison with the control group.
- A randomized, double-blind, placebo-controlled, prospective trial of 4038 patients with: CKD not on dialysis (eGFR of 20 – 60 mL/min), anemia (hemoglobin levels ≤ 11 g/dL), and type 2 diabetes mellitus, patients were randomized to receive either darbepoetin alfa treatment or a matching placebo. Placebo group patients also received darbepoetin alfa when their hemoglobin levels were below 9 g/dL. The trial objectives were to demonstrate the benefit of darbepoetin alfa treatment of the anemia to a target hemoglobin level of 13 g/dL, when compared to a "placebo" group, by reducing the occurrence of either of two primary endpoints: (1) a composite cardiovascular endpoint of all-cause mortality or a specified cardiovascular event (myocardial ischemia, CHF,MI, and CVA) or (2) a composite renal endpoint of all-cause mortality or progression to end stage renal disease. The overall risks for each of the two primary endpoints (the cardiovascular composite and the renal composite) were not reduced with darbepoetin alfa treatment (see Table 1), but the risk of stroke was increased nearly two-fold in the darbepoetin alfa -treated group versus the placebo group: annualized stroke rate 2.1% vs. 1.1%, respectively, HR 1.92; 95% CI: 1.38, 2.68; p < 0.001. The relative risk of stroke was particularly high in patients with a prior stroke: annualized stroke rate 5.2% in the darbepoetin alfa- treated group and 1.9% in the placebo group, HR 3.07; 95% CI: 1.44, 6.54. Also, among darbepoetin alfa -treated subjects with a past history of cancer, there were more deaths due to all causes and more deaths adjudicated as due to cancer, in comparison with the control group.
- Patients with Cancer
- An increased incidence of thromboembolic reactions, some serious and life-threatening, occurred in patients with cancer treated with ESAs.
- In a randomized, placebo-controlled study (Study 1 in Table 2) of 939 women with metastatic breast cancer receiving chemotherapy, patients received either weekly epoetin alfa or placebo for up to a year. This study was designed to show that survival was superior when epoetin alfa was administered to prevent anemia (maintain hemoglobin levels between 12 and 14 g/dL or hematocrit between 36% and 42%). This study was terminated prematurely when interim results demonstrated a higher mortality at 4 months (8.7% vs. 3.4%) and a higher rate of fatal thrombotic reactions (1.1% vs. 0.2%) in the first 4 months of the study among patients treated with epoetin alfa. Based on Kaplan-Meier estimates, at the time of study termination, the 12-month survival was lower in the epoetin alfa group than in the placebo group (70% vs. 76%; HR 1.37, 95% CI: 1.07, 1.75; p = 0.012).
- Patients Having Surgery
- An increased incidence of deep venous thrombosis (DVT) in patients receiving epoetin alfa undergoing surgical orthopedic procedures was demonstrated. In a randomized, controlled study, 680 adult patients, not receiving prophylactic anticoagulation and undergoing spinal surgery, were randomized to 4 doses of 600 Units/kg epoetin alfa (7, 14, and 21 days before surgery, and the day of surgery) and standard of care (SOC) treatment (n = 340) or to SOC treatment alone (n = 340). A higher incidence of DVTs, determined by either color flow duplex imaging or by clinical symptoms, was observed in the epoetin alfa group (16 patients) compared with the SOC group (7 patients). In addition to the 23 patients with DVTs included in the primary analysis, 19 patients (n = 680) experienced 1 other thrombovascular event (TVE) each (12 in the epoetin alfa group and 7 in the SOC group). Deep venous thrombosis prophylaxis is strongly recommended when ESAs are used for the reduction of allogeneic RBC transfusions in surgical patients.
- Increased mortality was observed in a randomized, placebo-controlled study of Epogen in adult patients who were undergoing CABG surgery (7 deaths in 126 patients randomized to Epogen versus no deaths among 56 patients receiving placebo). Four of these deaths occurred during the period of study drug administration and all 4 deaths were associated with thrombotic events.
- In order to prescribe and/or dispense Epogen to patients with cancer and anemia due to myelosuppressive chemotherapy, prescribers and hospitals must enroll in and comply with the ESA APPRISE Oncology Program requirements. To enroll, visit www.esa-apprise.com or call 1-866-284-8089 for further assistance. Additionally, prior to each new course of Epogen in patients with cancer, prescribers and patients must provide written acknowledgment of a discussion of the risks of Epogen.
- ESAs resulted in decreased locoregional control/progression-free survival and/or overall survival (see Table 2). These findings were observed in studies of patients with advanced head and neck cancer receiving radiation therapy (Studies 5 and 6), in patients receiving chemotherapy for metastatic breast cancer (Study 1) or lymphoid malignancy (Study 2), and in patients with non-small cell lung cancer or various malignancies who were not receiving chemotherapy or radiotherapy (Studies 7 and 8).
- Decreased Overall Survival
- Study 1 was described in the previous section. Mortality at 4 months (8.7% vs. 3.4%) was significantly higher in the epoetin alfa arm. The most common investigator-attributed cause of death within the first 4 months was disease progression; 28 of 41 deaths in the epoetin alfa arm and 13 of 16 deaths in the placebo arm were attributed to disease progression. Investigator-assessed time to tumor progression was not different between the 2 groups. Survival at 12 months was significantly lower in the epoetin alfa arm (70% vs. 76%; HR 1.37, 95% CI: 1.07, 1.75; p = 0.012).
- Study 2 was a randomized, double-blind study (darbepoetin alfa vs. placebo) conducted in 344 anemic patients with lymphoid malignancy receiving chemotherapy. With a median follow-up of 29 months, overall mortality rates were significantly higher among patients randomized to darbepoetin alfa as compared to placebo (HR 1.36, 95% CI: 1.02, 1.82).
- Study 7 was a multicenter, randomized, double-blind study (epoetin alfa vs. placebo) in which patients with advanced non-small cell lung cancer receiving only palliative radiotherapy or no active therapy were treated with epoetin alfa to achieve and maintain hemoglobin levels between 12 and 14 g/dL. Following an interim analysis of 70 patients (planned accrual 300 patients), a significant difference in survival in favor of the patients in the placebo arm of the study was observed (median survival 63 vs. 129 days; HR 1.84; p = 0.04).
- Study 8 was a randomized, double-blind study (darbepoetin alfa vs. placebo) in 989 anemic patients with active malignant disease, neither receiving nor planning to receive chemotherapy or radiation therapy. There was no evidence of a statistically significant reduction in proportion of patients receiving RBC transfusions. The median survival was shorter in the darbepoetin alfa treatment group than in the placebo group (8 months vs. 10.8 months; HR 1.30, 95% CI: 1.07, 1.57).
- Decreased Progression-free Survival and Overall Survival
- Study 3 was a randomized, open-label, controlled, factorial design study in which darbepoetin alfa was administered to prevent anemia in 733 women receiving neo-adjuvant breast cancer treatment. A final analysis was performed after a median follow-up of approximately 3 years. The 3-year survival rate was lower (86% vs. 90%; HR 1.42, 95% CI: 0.93, 2.18) and the 3-year relapse-free survival rate was lower (72% vs. 78%; HR 1.33, 95% CI: 0.99, 1.79) in the darbepoetin alfa-treated arm compared to the control arm.
- Study 4 was a randomized, open-label, controlled study that enrolled 114 of a planned 460 cervical cancer patients receiving chemotherapy and radiotherapy. Patients were randomized to receive epoetin alfa to maintain hemoglobin between 12 and 14 g/dL or to RBC transfusion support as needed. The study was terminated prematurely due to an increase in thromboembolic adverse reactions in epoetin alfa-treated patients compared to control (19% vs. 9%). Both local recurrence (21% vs. 20%) and distant recurrence (12% vs. 7%) were more frequent in epoetin alfa-treated patients compared to control. Progression-free survival at 3 years was lower in the epoetin alfa-treated group compared to control (59% vs. 62%; HR 1.06, 95% CI: 0.58, 1.91). Overall survival at 3 years was lower in the epoetin alfa-treated group compared to control (61% vs. 71%; HR 1.28, 95% CI: 0.68, 2.42).
- Study 5 was a randomized, placebo-controlled study in 351 head and neck cancer patients where epoetin beta or placebo was administered to achieve target hemoglobins ≥ 14 and ≥ 15 g/dL for women and men, respectively. Locoregional progression-free survival was significantly shorter in patients receiving epoetin beta (HR 1.62, 95% CI: 1.22, 2.14; p = 0.0008) with medians of 406 days and 745 days in the epoetin beta and placebo arms, respectively. Overall survival was significantly shorter in patients receiving epoetin beta (HR 1.39, 95% CI: 1.05, 1.84; p = 0.02).
- Decreased Locoregional Control
- Study 6 was a randomized, open-label, controlled study conducted in 522 patients with primary squamous cell carcinoma of the head and neck receiving radiation therapy alone (no chemotherapy) who were randomized to receive darbepoetin alfa to maintain hemoglobin levels of 14 to15.5 g/dL or no darbepoetin alfa. An interim analysis performed on 484 patients demonstrated that locoregional control at 5 years was significantly shorter in patients receiving darbepoetin alfa (RR 1.44, 95% CI: 1.06, 1.96; p = 0.02). Overall survival was shorter in patients receiving darbepoetin alfa (RR 1.28, 95% CI: 0.98, 1.68; p = 0.08).
- Epogen is contraindicated in patients with uncontrolled hypertension. Following initiation and titration of Epogen, approximately 25% of patients on dialysis required initiation of or increases in antihypertensive therapy; hypertensive encephalopathy and seizures have been reported in patients with CKD receiving Epogen.
- Appropriately control hypertension prior to initiation of and during treatment with Epogen. Reduce or withhold Epogen if blood pressure becomes difficult to control. Advise patients of the importance of compliance with antihypertensive therapy and dietary restrictions.
- Epogen increases the risk of seizures in patients with CKD. During the first several months following initiation of Epogen, monitor patients closely for premonitory neurologic symptoms. Advise patients to contact their healthcare practitioner for new-onset seizures, premonitory symptoms or change in seizure frequency.
- For lack or loss of hemoglobin response to Epogen, initiate a search for causative factors (e.g., iron deficiency, infection, inflammation, bleeding). If typical causes of lack or loss of hemoglobin response are excluded, evaluate for PRCA. In the absence of PRCA, follow dosing recommendations for management of patients with an insufficient hemoglobin response to Epogen therapy.
- Cases of PRCA and of severe anemia, with or without other cytopenias that arise following the development of neutralizing antibodies to erythropoietin have been reported in patients treated with Epogen. This has been reported predominantly in patients with CKD receiving ESAs by subcutaneous administration. PRCA has also been reported in patients receiving ESAs for anemia related to hepatitis C treatment (an indication for which Epogen is not approved).
- If severe anemia and low reticulocyte count develop during treatment with Epogen, withhold Epogen and evaluate patients for neutralizing antibodies to erythropoietin. Contact Amgen (1-800-77-AMGEN) to perform assays for binding and neutralizing antibodies. Permanently discontinue Epogen in patients who develop PRCA following treatment with Epogen or other erythropoietin protein drugs. Do not switch patients to other ESAs.
- Serious allergic reactions, including anaphylactic reactions, angioedema, bronchospasm, skin rash, and urticaria may occur with Epogen. Immediately and permanently discontinue Epogen and administer appropriate therapy if a serious allergic or anaphylactic reaction occurs.
- Epogen contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.
- Patients may require adjustments in their dialysis prescriptions after initiation of Epogen. Patients receiving Epogen may require increased anticoagulation with heparin to prevent clotting of the extracorporeal circuit during hemodialysis.
- Evaluate transferrin saturation and serum ferritin prior to and during Epogen treatment. Administer supplemental iron therapy when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20%. The majority of patients with CKD will require supplemental iron during the course of ESA therapy. Following initiation of therapy and after each dose adjustment, monitor hemoglobin weekly until the hemoglobin level is stable and sufficient to minimize the need for RBC transfusion.
# Adverse Reactions
## Clinical Trials Experience
- Increased Mortality, Myocardial Infarction, Stroke, and Thromboembolism
- Increased mortality and/or increased risk of tumor progression or recurrence in Patients With Cancer
- Hypertension
- Seizures
- PRCA
- Serious allergic reactions.
- Adult Patients
- Three double-blind, placebo-controlled studies, including 244 patients with CKD on dialysis, were used to identify the adverse reactions to Epogen. In these studies, the mean age of patients was 48 years (range: 20 to 80 years). One hundred and thirty-three (55%) patients were men. The racial distribution was as follows: 177 (73%) patients were white, 48 (20%) patients were black, 4 (2%) patients were Asian, 12 (5%) patients were other, and racial information was missing for 3 (1%) patients.
- Two double-blind, placebo-controlled studies, including 210 patients with CKD not on dialysis, were used to identify the adverse reactions to Epogen. In these studies, the mean age of patients was 57 years (range: 24 to 79 years). One hundred and twenty-one (58%) patients were men. The racial distribution was as follows: 164 (78%) patients were white, 38 (18%) patients were black, 3 (1%) patients were Asian, 3 (1%) patients were other, and racial information was missing for 2 (1%) patients.
- The adverse reactions with a reported incidence of ≥ 5% in Epogen-treated patients and that occurred at a ≥ 1% higher frequency than in placebo-treated patients are shown in the table below:
- An additional serious adverse reaction that occurred in less than 5% of epoetin alfa-treated dialysis patients and greater than placebo was thrombosis (2.7% Epogen and 1% placebo).
- The adverse reactions with a reported incidence of ≥ 5% in Epogen-treated patients and that occurred at a ≥ 1% higher frequency than in placebo-treated patients are shown in the table below:
- Additional serious adverse reactions that occurred in less than 5% of epoetin alfa-treated patients not on dialysis and greater than placebo were erythema (0.8% Epogen and 0% placebo) and myocardial infarction (0.8% Epogen and 0% placebo).
- Pediatric Patients
- In pediatric patients with CKD on dialysis, the pattern of adverse reactions was similar to that found in adults.
- A total of 297 zidovudine-treated HIV-infected patients were studied in 4 placebo-controlled studies. A total of 144 (48%) patients were randomly assigned to receive Epogen and 153 (52%) patients were randomly assigned to receive placebo. Epogen was administered at doses between 100 and 200 Units/kg 3 times weekly subcutaneously for up to 12 weeks.
- For the combined Epogen treatment groups, a total of 141 (98%) men and 3 (2%) women between the ages of 24 and 64 years were enrolled. The racial distribution of the combined Epogen treatment groups was as follows: 129 (90%) white, 8 (6%) black, 1 (1%) Asian, and 6 (4%) other.
- In double-blind, placebo-controlled studies of 3 months duration involving approximately 300 zidovudine-treated HIV-infected patients, adverse reactions with an incidence of ≥ 1% in patients treated with Epogen were:
- The data below were obtained in Study C1, a 16-week, double-blind, placebo-controlled study that enrolled 344 patients with anemia secondary to chemotherapy. There were 333 patients who were evaluable for safety; 168 of 174 patients (97%) randomized to Epogen received at least 1 dose of study drug, and 165 of 170 patients (97%) randomized to placebo received at least 1 placebo dose. For the once weekly Epogen-treatment group, a total of 76 men (45%) and 92 women (55%) between the ages of 20 and 88 years were treated. The racial distribution of the Epogen-treatment group was 158 white (94%) and 10 black (6%). Epogen was administered once weekly for an average of 13 weeks at a dose of 20,000 to 60,000 IU subcutaneously (mean weekly dose was 49,000 IU).
- The adverse reactions with a reported incidence of ≥ 5% in Epogen-treated patients that occurred at a higher frequency than in placebo-treated patients are shown in the table below:
- Four hundred sixty-one patients undergoing major orthopedic surgery were studied in a placebo-controlled study (S1) and a comparative dosing study (2 dosing regimens, S2). A total of 358 patients were randomly assigned to receive Epogen and 103 (22%) patients were randomly assigned to receive placebo. Epogen was administered daily at a dose of 100 to 300 IU/kg subcutaneously for 15 days or at 600 IU/kg once weekly for 4 weeks.
- For the combined Epogen treatment groups, a total of 90 (25%) and 268 (75%) women between the ages of 29 and 89 years were enrolled. The racial distribution of the combined Epogen treatment groups was as follows: 288 (80%) white, 64 (18%) black, 1 (< 1%) Asian, and 5 (1%) other.
- The adverse reactions with a reported incidence of ≥ 1% in Epogen-treated patients that occurred at a higher frequency than in placebo-treated patients are shown in the table below:
## Postmarketing Experience
- Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- The following adverse reactions have been identified during postmarketing use of Epogen:
- Seizures
- PRCA
- Serious allergic reactions
- Injection site reactions, including irritation and pain
- Porphyria
# Drug Interactions
- No formal drug interaction studies have been conducted with Epogen.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
- Pregnancy Category C
- There are no adequate and well-controlled studies of Epogen use during pregnancy. There are limited data on Epogen use in pregnant women. In animal reproductive and developmental toxicity studies, adverse fetal effects occurred when pregnant rats received epoetin alfa at doses approximating the clinical recommended starting doses. Single-dose formulations of Epogen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- There are reports of at least 33 pregnant women with anemia alone or anemia associated with severe renal disease and other hematologic disorders who received Epogen. Polyhydramnios and intrauterine growth restriction were reported in women with chronic renal disease, which is associated with an increased risk for these adverse pregnancy outcomes. There was 1 infant born with pectus excavatum and hypospadias following exposure during the first trimester. Due to the limited number of exposed pregnancies and multiple confounding factors (such as underlying maternal conditions, other maternal medications, and gestational timing of exposure), these published case reports and studies do not reliably estimate the frequency or absence of adverse outcomes.
- When healthy rats received Epogen at doses of 100 Units/kg/day during mating and through early pregnancy (dosing stopped prior to organogenesis), there were slight increases in the incidences of pre-and post-implantation loss, and a decrease in live fetuses. This animal dose level of 100 Units/kg/day may approximate the clinical recommended starting dose, depending on the treatment indication. When healthy pregnant rats and rabbits received intravenous doses of up to 500 mg/kg/day of Epogen only during organogenesis, no teratogenic effects were observed in the offspring.
- When healthy pregnant rats received Epogen at doses of 500 Units/kg/day late in pregnancy (after the period of organogenesis), offspring had decreased number of caudal vertebrae and growth delays.
- Women who become pregnant during Epogen treatment are encouraged to enroll in Amgen’s Pregnancy Surveillance Program. Patients or their physicians should call 1-800-772-6436 (1-800-77-AMGEN) to enroll.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Epoetin in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Epoetin during labor and delivery.
### Nursing Mothers
- The multidose vials of Epogen are formulated with benzyl alcohol. Do not administer Epogen from multidose vials, or Epogen from single-dose vials admixed with bacteriostatic saline containing benzyl alcohol, to a nursing woman. When therapy with Epogen is needed in nursing women, use a benzyl alcohol-free formulation.
- It is not known whether Epogen is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Epogen from single-dose vials is administered to a nursing woman.
### Pediatric Use
- The multidose vials are formulated with benzyl alcohol. Do not administer Epogen from multidose vials, or Epogen from single-dose vials admixed with bacteriostatic saline containing benzyl alcohol, to neonates or infants. When therapy with Epogen is needed in neonates and infants, use a benzyl alcohol-free formulation.
- Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. The "gasping syndrome," (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages > 99 mg/kg/day in neonates and low-birthweight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse.
- Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the "gasping syndrome", the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birthweight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.
- Pediatric Patients on Dialysis
- Epogen is indicated in pediatric patients, ages 1 month to 16 years of age, for the treatment of anemia associated with CKD requiring dialysis. Safety and effectiveness in pediatric patients less than 1 month old have not been established.
- The safety data from these studies are similar to those obtained from the studies of Epogen in adult patients with CKD.
- Pediatric Cancer Patients on Chemotherapy
- Epogen is indicated in patients 5 to 18 years old for the treatment of anemia due to concomitant myelosuppressive chemotherapy. Safety and effectiveness in pediatric patients less than 5 years of age have not been established. The safety data from these studies are similar to those obtained from the studies of Epogen in adult patients with cancer.
- Pediatric Patients With HIV Infection Receiving Zidovudine
- Published literature has reported the use of Epogen in 20 zidovudine-treated, anemic, pediatric patients with HIV infection, ages 8 months to 17 years, treated with 50 to 400 Units/kg subcutaneously or intravenously 2 to 3 times per week. Increases in hemoglobin levels and in reticulocyte counts and decreases in or elimination of RBC transfusions were observed.
- Pharmacokinetics in Neonates
- Limited pharmacokinetic data from a study of 7 preterm, very low birth weight neonates and 10 healthy adults given intravenous erythropoietin suggested that distribution volume was approximately 1.5 to 2 times higher in the preterm neonates than in the healthy adults, and clearance was approximately 3 times higher in the preterm neonates than in the healthy adults.
### Geriatic Use
- Of the 4553 patients who received Epogen in the 6 studies for treatment of anemia due to CKD not receiving dialysis, 2726 (60%) were age 65 years and over, while 1418 (31%) were 75 years and over. Of the 757 patients who received Epogen in the 3 studies of CKD patients on dialysis, 361 (47%) were age 65 years and over, while 100 (13%) were 75 years and over. No differences in safety or effectiveness were observed between geriatric and younger patients. Dose selection and adjustment for an elderly patient should be individualized to achieve and maintain the target hemoglobin.
- Among 778 patients enrolled in the 3 clinical studies of Epogen for the treatment of anemia due to concomitant chemotherapy, 419 received Epogen and 359 received placebo. Of the 419 who received Epogen, 247 (59%) were age 65 years and over, while 78 (19%) were 75 years and over. No overall differences in safety or effectiveness were observed between geriatric and younger patients. The dose requirements for Epogen in geriatric and younger patients within the 3 studies were similar.
- Among 1731 patients enrolled in the 6 clinical studies of Epogen for reduction of allogeneic RBC transfusions in patients undergoing elective surgery, 1085 received Epogen and 646 received placebo or standard of care treatment. Of the 1085 patients who received Epogen, 582 (54%) were age 65 years and over, while 245 (23%) were 75 years and over. No overall differences in safety or effectiveness were observed between geriatric and younger patients. The dose requirements for Epogen in geriatric and younger patients within the 4 studies using the 3 times weekly schedule and 2 studies using the weekly schedule were similar.
- Insufficient numbers of patients age 65 years or older were enrolled in clinical studies of Epogen for the treatment of zidovudine in HIV-infected patients to determine whether they respond differently from younger patients.
### Gender
There is no FDA guidance on the use of Epoetin with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Epoetin with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Epoetin in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Epoetin in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Epoetin in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Epoetin in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Subcutaneous
- Intravenous
### Monitoring
- To undergo regular blood pressure monitoring.
- Evaluate transferrin saturation and serum ferritin prior to and during Epogen treatment.
- Epogen increases the risk for seizures in patients with CKD. Increase monitoring of these patients for changes in seizure frequency or premonitory symptoms
# IV Compatibility
There is limited information regarding IV Compatibility of Epoetin in the drug label.
# Overdosage
- Epogen overdosage can cause hemoglobin levels above the desired level, which should be managed with discontinuation or reduction of Epogen dosage and/or with phlebotomy as clinically indicated.
- Cases of severe hypertension have been observed following overdose with ESAs
## Chronic Overdose
There is limited information regarding Chronic Overdose of Epoetin in the drug label.
# Pharmacology
## Mechanism of Action
- Epogen stimulates erythropoiesis by the same mechanism as endogenous erythropoietin.
## Structure
- Epogen (epoetin alfa) is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin.
- Epogen is formulated as a sterile, colorless liquid in vials in multiple formulations. Single-dose vials, formulated with an isotonic sodium chloride/sodium citrate-buffered solution, are supplied in multiple strengths. Each 1 mL vial contains 2000, 3000, 4000, or 10,000 Units of epoetin alfa, Albumin (Human) (2.5 mg), citric acid (0.06 mg), sodium chloride (5.9 mg), and sodium citrate (5.8 mg) in Water for Injection, USP (pH 6.9 ± 0.3). Single-dose 1 mL vials formulated with an isotonic sodium chloride/sodium phosphate buffer contain 40,000 Units of epoetin alfa albumin (human) (2.5 mg), citric acid (0.0068 mg), sodium chloride (5.8 mg), sodium citrate (0.7 mg), sodium phosphate dibasic anhydrate (1.8 mg), and sodium phosphate monobasic monohydrate (1.2 mg) in Water for Injection, USP (pH 6.9 ± 0.3). Multidose, 2 mL vials contain 10,000 Units epoetin alfa, albumin (human) (2.5 mg), benzyl alcohol (1%), sodium chloride (8.2 mg), and sodium citrate (1.3 mg) per 1 mL Water for Injection, USP (pH 6.1 ± 0.3). Multidose 1 mL vials contain 20,000 Units epoetin alfa, albumin (human) (2.5 mg), benzyl alcohol (1%), sodium chloride (8.2 mg), citric acid (0.11 mg), and sodium citrate (1.3 mg), per 1 mL in Water for Injection, USP (pH 6.1 ± 0.3).
## Pharmacodynamics
- Epogen increases the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks. The rate of hemoglobin increase varies among patients and is dependent upon the dose of Epogen administered. For correction of anemia in hemodialysis patients, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly.
## Pharmacokinetics
- In adult and pediatric patients with CKD, the elimination half-life (t1/2) of plasma erythropoietin after intravenous administration of Epogen ranged from 4 to 13 hours. After subcutaneous administration, Cmax was achieved within 5 to 24 hours. The t1/2 in adult patients with serum creatinine greater than 3 mg/dL was similar between those not on dialysis and those maintained on dialysis. The pharmacokinetic data indicate no apparent difference in Epogen t1/2 among adult patients above or below 65 years of age.
- A pharmacokinetic study comparing 150 Units/kg subcutaneous 3 times weekly to 40,000 Units subcutaneous weekly dosing regimen was conducted for 4 weeks in healthy subjects (n = 12) and for 6 weeks in anemic cancer patients (n = 32) receiving cyclic chemotherapy. There was no accumulation of serum erythropoietin after the 2 dosing regimens during the study period. The 40,000 Units weekly regimen had a higher Cmax (3- to 7-fold), longer Tmax (2- to 3-fold), higher AUC0-168 h (2- to 3-fold) of erythropoietin and lower clearance (CL) (50%) than the 150 Units/kg 3 times weekly regimen. In anemic cancer patients, the average t1/2 was similar (40 hours with range of 16 to 67 hours) after both dosing regimens. After the 150 Units/kg 3 times weekly dosing, the values of Tmax and CL were similar (13.3 ± 12.4 vs. 14.2 ± 6.7 hours, and 20.2 ± 15.9 vs. 23.6 ± 9.5 mL/hr/kg) between week 1 when patients were receiving chemotherapy (n = 14) and week 3 when patients were not receiving chemotherapy (n = 4). Differences were observed after the 40,000 Units weekly dosing with longer Tmax (38 ± 18 hours) and lower CL (9.2 ± 4.7 mL/hr/kg) during week 1 when patients were receiving chemotherapy (n = 18) compared with those (22 ± 4.5 hours, 13.9 ± 7.6 mL/hr/kg, respectively) during week 3 when patients were not receiving chemotherapy (n = 7).
- The pharmacokinetic profile of Epogen in children and adolescents appeared similar to that of adults.
- The pharmacokinetics of Epogen has not been studied in patients with HIV infection.
## Nonclinical Toxicology
- Carcinogenicity
- The carcinogenic potential of Epogen has not been evaluated.
- Mutagenicity
- Epogen was not mutagenic or clastogenic under the conditions tested: Epogen was negative in the in vitro bacterial reverse mutation assay (Ames test), in the in vitro mammalian cell gene mutation assay (the hypoxanthine-guanine phosphoribosyl transferase locus), in an in vitro chromosomal aberration assay in mammalian cells, and in the in vivo mouse micronucleus assay.
- Impairment of Fertility
- When administered intravenously to male and female rats prior to and during mating, and to females through the beginning of implantation (up to gestational day 7; dosing stopped prior to the beginning of organogenesis), doses of 100 and 500 Units/kg/day of Epogen caused slight increases in pre-implantation loss, post-implantation loss and decreases in the incidence of live fetuses. It is not clear whether these effects reflect a drug effect on the uterine environment or on the conceptus. This animal dose level of 100 Units/kg/day approximates the clinical recommended starting dose, depending on the patient’s treatment indication, but may be lower than the clinical dose in patients whose doses have been adjusted.
- When pregnant rats were administered intravenous Epogen, 500 Units/kg/day, after the period of organogenesis (from day 17 of gestation through day 21 of lactation), their pups exhibited decreased number of caudal vertebrae, decreased body weight gain, and delayed appearance of abdominal hair, eyelid opening, and ossification. This animal dose level of 500 Units/kg/day is approximately 5-fold higher than the clinical recommended starting dose, depending on the patient’s treatment indication.
- When Epogen was administered intravenously during the period of organogenesis to pregnant rats (gestational days 7 to 17) and pregnant rabbits (gestational days 6 to 18), no evidence of teratogenic outcome was observed at the doses tested, up to 500 Units/kg/day. The offspring (F1 generation) of the treated rats were observed postnatally; rats from the F1 generation reached maturity and were mated; no Epogen-related effects were apparent for their offspring (F2 generation fetuses).
# Clinical Studies
- Adult Patients on Dialysis
- Patients with chronic kidney disease on dialysis: ESA effects on rates of transfusion
- In clinical studies of CKD patients on dialysis, Epogen increased hemoglobin levels and decreased the need for RBC transfusion. Overall, more than 95% of patients were RBC transfusion-independent after receiving Epogen for 3 months. In clinical studies at starting doses of 50 to 150 Units/kg 3 times weekly, adult patients responded with an average rate of hemoglobin rise as presented in Table 8.
- The safety and efficacy of Epogen were evaluated in 13 clinical studies involving intravenous administration to a total of 1010 anemic patients on dialysis. Overall, more than 90% of the patients treated with Epogen experienced improvement in hemoglobin concentrations. In the 3 largest of these clinical studies, the median maintenance dose necessary to maintain the hemoglobin between 10 to 12 g/dL was approximately 75 Units/kg 3 times weekly. More than 95% of patients were able to avoid RBC transfusions. In the largest US multicenter study, approximately 65% of the patients received doses of 100 Units/kg 3 times weekly or less to maintain their hemoglobin at approximately 11.7 g/dL. Almost 10% of patients received a dose of 25 Units/kg or less, and approximately 10% received a dose of more than 200 Units/kg 3 times weekly to maintain their hemoglobin at this level.
- In the Normal Hematocrit Study, the yearly transfusion rate was 51.5% in the lower hemoglobin group (10 g/dL) and 32.4% in the higher hemoglobin group (14 g/dL).
- Other ESA trials
- In a 26-week, double-blind, placebo-controlled study, 118 patients on dialysis with an average hemoglobin of approximately 7 g/dL were randomized to either Epogen or placebo. By the end of the study, average hemoglobin increased to approximately 11 g/dL in the Epogen-treated patients and remained unchanged in patients receiving placebo. Epogen-treated patients experienced improvements in exercise tolerance and patient-reported physical functioning at month 2 that were maintained throughout the study.
- A multicenter, unit-dose study was also conducted in 119 patients receiving peritoneal dialysis who self-administered Epogen subcutaneously. Patients responded to Epogen administered subcutaneously in a manner similar to patients receiving intravenous administration.
- The safety and efficacy of Epogen were studied in a placebo-controlled, randomized study of 113 children with anemia (hemoglobin ≤ 9 g/dL) undergoing peritoneal dialysis or hemodialysis. The initial dose of Epogen was 50 Units/kg intravenously or subcutaneously 3 times weekly. The dose of study drug was titrated to achieve either a hemoglobin of 10 to 12 g/dL or an absolute increase in hemoglobin of 2 g/dL over baseline.
- At the end of the initial 12 weeks, a statistically significant rise in mean hemoglobin (3.1 g/dL vs. 0.3 g/dL) was observed only in the Epogen arm. The proportion of children achieving a hemoglobin of 10 g/dL, or an increase in hemoglobin of 2 g/dL over baseline, at any time during the first 12 weeks was higher in the Epogen arm (96% vs. 58%). Within 12 weeks of initiating Epogen therapy, 92.3% of the pediatric patients were RBC transfusion independent as compared to 65.4% who received placebo. Among patients who received 36 weeks of Epogen, hemodialysis patients received a higher median maintenance dose and took longer to achieve a hemoglobin of 10 to 12 g/dL (median time to response 69 days vs. 32 days) than patients undergoing peritoneal dialysis.
- Four clinical studies were conducted in patients with CKD not on dialysis involving 181 patients treated with Epogen. These patients responded to Epogen therapy in a manner similar to that observed in patients on dialysis. Patients with CKD not on dialysis demonstrated a dose-dependent and sustained increase in hemoglobin when Epogen was administered by either an intravenous or subcutaneous route, with similar rates of rise of hemoglobin when Epogen was administered by either route.
- In TREAT, a randomized, double-blind trial of 4038 patients with CKD and type 2 diabetes not on dialysis, a post-hoc analysis showed that the proportion of patients receiving RBC transfusions was lower in patients administered an ESA to target a hemoglobin of 13 g/dL compared to the control arm in which an ESA was administered intermittently if hemoglobin concentration decreased to less than 9 g/dL (15% versus 25%, respectively). In CHOIR, a randomized open-label study of 1432 patients with CKD not on dialysis, use of epoetin alfa to target a higher (13.5 g/dL) versus lower (11.3 g/dL) hemoglobin goal did not reduce the use of RBC transfusions. In each trial, no benefits occurred for the cardiovascular or end-stage renal disease outcomes. In each trial, the potential benefit of ESA therapy was offset by worse cardiovascular safety outcomes resulting in an unfavorable benefit-risk profile.
- ESA Effects on rates of death and other serious cardiac adverse events
- Three randomized outcome trials (Normal Hematocrit Study , Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease , and Trial of Darbepoetin Alfa in Type 2 Diabetes and CKD ) have been conducted in patients with CKD using Epogen/PROCRIT/Aranesp to target higher vs. lower hemoglobin levels. Though these trials were designed to establish a cardiovascular or renal benefit of targeting higher hemoglobin levels, in all 3 studies, patients randomized to the higher hemoglobin target experienced worse cardiovascular outcomes and showed no reduction in progression to ESRD. In each trial, the potential benefit of ESA therapy was offset by worse cardiovascular safety outcomes resulting in an unfavorable benefit-risk profile.
- The safety and efficacy of Epogen were evaluated in 4 placebo-controlled studies enrolling 297 anemic patients (hemoglobin < 10 g/dL) with HIV infection receiving concomitant therapy with zidovudine. In the subgroup of patients (89/125 Epogen and 88/130 placebo) with pre study endogenous serum erythropoietin levels ≤ 500 mUnits/mL, Epogen reduced the mean cumulative number of units of blood transfused per patient by approximately 40% as compared to the placebo group. Among those patients who required RBC transfusions at baseline, 43% of patients treated with Epogen versus 18% of placebo-treated patients were RBC transfusion independent during the second and third months of therapy. Epogen therapy also resulted in significant increases in hemoglobin in comparison to placebo. When examining the results according to the weekly dose of zidovudine received during month 3 of therapy, there was a statistically significant reduction (p < 0.003) in RBC transfusion requirements in patients treated with Epogen (n = 51) compared to placebo-treated patients (n = 54) whose mean weekly zidovudine dose was ≤ 4200 mg/week.
- Approximately 17% of the patients with endogenous serum erythropoietin levels ≤ 500 mUnits/mL receiving Epogen in doses from 100 to 200 Units/kg 3 times weekly achieved a hemoglobin of 12.7 g/dL without administration of RBC transfusions or significant reduction in zidovudine dose. In the subgroup of patients whose pre study endogenous serum erythropoietin levels were > 500 mUnits/mL, Epogen therapy did not reduce RBC transfusion requirements or increase hemoglobin compared to the corresponding responses in placebo-treated patients.
- The safety and effectiveness of Epogen was assessed in two multicenter, randomized (1:1), placebo-controlled, double-blind studies (Study C1 and Study C2) and a pooled analysis of six additional randomized (1:1), multicenter, placebo-controlled, double-blind studies. All studies were conducted in patients with anemia due to concomitantly administered cancer chemotherapy. Study C1 enrolled 344 adult patients, Study C2 enrolled 222 pediatric patients, and the pooled analysis contained 131 patients randomized to epoetin alfa or placebo. In Studies C1 and C2, efficacy was demonstrated by a reduction in the proportion of patients who received an RBC transfusion, from week 5 through end of the study, with the last-known RBC transfusion status carried forward for patients who discontinued treatment. In the pooled analysis, efficacy was demonstrated by a reduction in the proportion of patients who received an RBC transfusion from week 5 through end of the study in the subset of patients who were remaining on therapy for 6 or more weeks.
- Study C1
- Study C1 was conducted in anemic patients (hemoglobin < 11.5 g/dL for males; < 10.5 g/dL for females) with non-myeloid malignancies receiving myelosuppressive chemotherapy. Randomization was stratified by type of malignancy (lung vs. breast vs. other), concurrent radiation therapy planned (yes or no), and baseline hemoglobin (< 9 g/dL vs. ≥ 9 g/dL); patients were randomized to epoetin alfa 40,000 Units (n = 174) or placebo (n = 170) as a weekly subcutaneous injection commencing on the first day of the chemotherapy cycle.
- Ninety-one percent of patients were white, 44% were male, and the median age of patients was 66 years (range: 20 to 88 years). The proportion of patients withdrawn from the study prior to week 5 was less than 10% for placebo-treated or epoetin-treated patients. Per protocol, the last available hemoglobin values from patients who dropped out were included in the efficacy analyses. Efficacy results are shown in Table 9.
- Study C2
- Study C2 was conducted in 222 anemic patients, ages 5 to 18, receiving chemotherapy for the treatment of various childhood malignancies. Randomization was stratified by cancer type (solid tumors, Hodgkin’s disease, acute lymphocytic leukemia, vs. non-Hodgkin’s lymphoma); patients were randomized to receive epoetin alfa at 600 Units/kg maximum 40,000 Units (n = 111) or placebo (n = 111) as a weekly intravenous injection.
- Sixty-nine percent of patients were white, 55% were male, and the median age of patients was 12 years (range: 5 to 18 years). Two (2%) of placebo-treated patients and 3 (3%) of epoetin alfa-treated patients dropped out of the study prior to week 5. There were fewer RBC transfusions from week 5 through the end-of-study in epoetin-alfa treated patients compared to placebo-treated patients . There was no evidence of an improvement in health-related quality of life, including no evidence of an effect on fatigue, energy, or strength in patients receiving Epogen as compared to those receiving placebo.
- Pooled Analysis (Three Times Per Week Dosing)
- The results of 6 studies of similar design and that randomized 131 patients to epoetin alfa or placebo were pooled to assess the safety and effectiveness of epoetin alfa. Patients were randomized to receive epoetin alfa at 150 Units/kg (n = 63) or placebo (n = 68), subcutaneously three times per week for 12 weeks in each study. Across all studies, 72 patients were treated with concomitant non cisplatin-containing chemotherapy regimens and 59 patients were treated with concomitant cisplatin-containing chemotherapy regimens. Twelve patients (19%) in the epoetin alfa arm and 10 patients (15%) in the placebo-arm dropped out prior to week 6 and are excluded from efficacy analyses.
- The safety and efficacy of Epogen were evaluated in a placebo-controlled, double-blind study (S1) enrolling 316 patients scheduled for major, elective orthopedic hip or knee surgery who were expected to require ≥ 2 units of blood and who were not able or willing to participate in an autologous blood donation program. Patients were stratified into 1 of 3 groups based on their pretreatment hemoglobin and then randomly assigned to receive 300 Units/kg Epogen, 100 Units/kg Epogen, or placebo by subcutaneous injection for 10 days before surgery, on the day of surgery, and for 4 days after surgery. All patients received oral iron and a low-dose, postoperative warfarin regimen.
- Treatment with Epogen 300 Units/kg significantly (p = 0.024) reduced the risk of allogeneic RBC transfusion in patients with a pretreatment hemoglobin of > 10 to ≤ 13 g/dL; 5/31 (16%) of patients treated with Epogen 300 Units/kg, 6/26 (23%) of patients treated with Epogen 100 Units/kg, and 13/29 (45%) of placebo-treated patients were transfused. There was no significant difference in the number of patients transfused between Epogen (9% 300 Units/kg, 6% 100 Units/kg) and placebo (13%) in the > 13 to ≤ 15 g/dL hemoglobin stratum. There were too few patients in the ≤ 10 g/dL group to determine if Epogen is useful in this hemoglobin strata. In the > 10 to ≤ 13 g/dL pretreatment stratum, the mean number of units transfused per Epogen-treated patient (0.45 units blood for 300 Units/kg, 0.42 units blood for 100 Units/kg) was less than the mean transfused per placebo-treated patient (1.14 units) (overall p = 0.028). In addition, mean hemoglobin, hematocrit, and reticulocyte counts increased significantly during the presurgery period in patients treated with Epogen.
- Epogen was also evaluated in an open-label, parallel-group study (S2) enrolling 145 patients with a pretreatment hemoglobin level of ≥ 10 to ≤ 13 g/dL who were scheduled for major orthopedic hip or knee surgery and who were not participating in an autologous program. Patients were randomly assigned to receive 1 of 2 subcutaneous dosing regimens of Epogen (600 Units/kg once weekly for 3 weeks prior to surgery and on the day of surgery, or 300 Units/kg once daily for 10 days prior to surgery, on the day of surgery, and for 4 days after surgery). All patients received oral iron and appropriate pharmacologic anticoagulation therapy.
- From pretreatment to presurgery, the mean increase in hemoglobin in the 600 Units/kg weekly group (1.44 g/dL) was greater than that observed in the 300 Units/kg daily group. The mean increase in absolute reticulocyte count was smaller in the weekly group (0.11 × 106/mm3) compared to the daily group (0.17 × 106/mm3). Mean hemoglobin levels were similar for the 2 treatment groups throughout the postsurgical period.
- The erythropoietic response observed in both treatment groups resulted in similar RBC transfusion rates . The mean number of units transfused per patient was approximately 0.3 units in both treatment groups.
# How Supplied
- Store at 36ºF to 46ºF (2ºC to 8ºC). Do not freeze.
- Do not shake. Protect from light; store Epogen in the carton until use.
- Do not use Epogen that has been shaken or frozen.
- Single-dose, Preservative-free Vial (in citrate-buffered formulation): 1 mL of solution contains 2000 (NDC 55513-126-10), 3000 (NDC 55513-267-10), 4000 (NDC 55513-148-10), or 10,000 Units (NDC 55513-144-10) of epoetin alfa. Each strength is supplied in dispensing packs containing 10 single-dose vials.
- Single-dose, Preservative-free Vial (in phosphate-buffered formulation): 1 mL of solution contains 40,000 Units (NDC 55513-823-10) of epoetin alfa and is supplied in dispensing packs containing 10 single-dose vials.
- Multidose, Preserved Vial: 2 mL total volume (20,000 Units total; 10,000 Units/mL). Each 1 mL of solution contains 10,000 Units (NDC 55513-283-10) of epoetin alfa, and is supplied in dispensing packs containing 10 multidose vials.
- Multidose, Preserved Vial: 1 mL total volume (20,000 Units/mL). Each 1 mL of solution contains 20,000 Units (NDC 55513-478-10) of epoetin alfa and is supplied in dispensing packs containing 10 multidose vials.
## Storage
There is limited information regarding Epoetin Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
# Precautions with Alcohol
- Alcohol-Epoetin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Epogen®
# Look-Alike Drug Names
There is limited information regarding Epoetin Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Epoetin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, M.B.B.S. [2]
# Disclaimer
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# Black Box Warning
# Overview
Epoetin is an erythropoiesis-stimulating agent (ESA) that is FDA approved for the treatment of anemia due to chronic kidney disease, anemia due to zidovudine in HIV-infected patients, anemia due to chemotherapy in patients with cancer, reduction of allogeneic red blood cell transfusions in patients undergoing elective, noncardiac, nonvascular surgery. There is a Black Box Warning for this drug as shown here. Common adverse reactions include edema, injection site irritation, injection site pain, pruritus, rash, nausea, vomiting, arthralgia, myalgia, dizziness, headache, insomnia, cough, upper respiratory infection, fever.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Evaluate the iron status in all patients before and during treatment and maintain iron repletion. Correct or exclude other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding, etc.) before initiating Epogen
- Epogen is indicated for the treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and not on dialysis to decrease the need for red blood cell (RBC) transfusion.
- In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL. No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks. Individualize dosing and use the lowest dose of Epogen sufficient to reduce the need for RBC transfusions. *Physicians and patients should weigh the possible benefits of decreasing transfusions against the increased risks of death and other serious cardiovascular adverse events.
- When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly. When adjusting therapy consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability. A single hemoglobin excursion may not require a dosing change.
- Do not increase the dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently. Avoid frequent dose adjustments.
- If the hemoglobin rises rapidly (e.g., more than 1 g/dL in any 2-week period), reduce the dose of Epogen by 25% or more as needed to reduce rapid responses.
- For patients who do not respond adequately, if the hemoglobin has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%.
- For patients who do not respond adequately over a 12-week escalation period, increasing the Epogen dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin level sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia. Discontinue Epogen if responsiveness does not improve.
- Initiate Epogen treatment when the hemoglobin level is less than 10 g/dL.
- If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of Epogen.
- The recommended starting dose for adult patients is 50 to 100 Units/kg 3 times weekly intravenously or subcutaneously. For pediatric patients, a starting dose of 50 Units/kg 3 times weekly intravenously or subcutaneously is recommended. The intravenous route is recommended for patients on hemodialysis.
- Consider initiating Epogen treatment only when the hemoglobin level is less than 10 g/dL and the following considerations apply:
- The rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion and,
- Reducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal
- If the hemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of Epogen, and use the lowest dose of Epogen sufficient to reduce the need for RBC transfusions.
- The recommended starting dose for adult patients is 50 to 100 Units/kg 3 times weekly intravenously or subcutaneously.
- Epogen is indicated for the treatment of anemia due to zidovudine administered at ≤ 4200 mg/week in HIV-infected patients with endogenous serum erythropoietin levels of ≤ 500 mUnits/mL.
- Starting Dose
- The recommended starting dose in adults is 100 Units/kg as an intravenous or subcutaneous injection 3 times per week.
- Dose Adjustment
- If hemoglobin does not increase after 8 weeks of therapy, increase Epogen dose by approximately
- 50 to 100 Units/kg at 4- to 8-week intervals until hemoglobin reaches a level needed to avoid RBC transfusions or 300 Units/kg.
- Withhold Epogen if hemoglobin exceeds 12 g/dL. Resume therapy at a dose 25% below the previous dose when hemoglobin declines to less than 11 g/dL.
- Discontinue Epogen if an increase in hemoglobin is not achieved at a dose of 300 Units/kg for 8 weeks.
- Epogen is indicated for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy.
- Initiate Epogen in patients on cancer chemotherapy only if the hemoglobin is less than 10 g/dL, and if there is a minimum of two additional months of planned chemotherapy.
- Use the lowest dose of Epogen necessary to avoid RBC transfusions.
- Recommended Starting Dose
- Adults:
- 150 Units/kg subcutaneously 3 times per week until completion of a chemotherapy course or
- 40,000 Units subcutaneously weekly until completion of a chemotherapy course.
- Dose Reduction
- Reduce dose by 25% if:
- Hemoglobin increases greater than 1 g/dL in any 2-week period or
- Hemoglobin reaches a level needed to avoid RBC transfusion.
- Withhold dose if hemoglobin exceeds a level needed to avoid RBC transfusion. Reinitiate at a dose 25% below the previous dose when hemoglobin approaches a level where RBC transfusions may be required.
- Dose Increase
- After the initial 4 weeks of Epogen therapy, if hemoglobin increases by less than 1 g/dL and remains below 10 g/dL, increase dose to:
- 300 Units/kg three times per week in adults or
- 60,000 Units weekly in adults
- 900 Units/kg (maximum 60,000 Units) weekly in children
- After 8 weeks of therapy, if there is no response as measured by hemoglobin levels or if RBC transfusions are still required, discontinue Epogen.
- Epogen is indicated to reduce the need for allogeneic RBC transfusions among patients with perioperative hemoglobin > 10 to ≤ 13 g/dL who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery. Epogen is not indicated for patients who are willing to donate autologous blood pre-operatively.
- 300 Units/kg per day subcutaneously for 15 days total: administered daily for 10 days before surgery, on the day of surgery, and for 4 days after surgery.
- 600 Units/kg subcutaneously in 4 doses administered 21, 14, and 7 days before surgery and on the day of surgery.
- Deep venous thrombosis prophylaxis is recommended during Epogen therapy.
- Do not shake. Do not use Epogen that has been shaken or frozen.
- Protect vials from light.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use any vials exhibiting particulate matter or discoloration.
- Discard unused portions of Epogen in preservative-free vials. Do not re-enter preservative-free vials.
- Store unused portions of Epogen in multidose vials at 36°F to 46° F (2°C to 8°C). Discard 21 days after initial entry.
- Do not dilute. Do not mix with other drug solutions except for admixing as described below:
- Preservative-free Epogen from single-use vials may be admixed in a syringe with bacteriostatic 0.9% sodium chloride injection, USP, with benzyl alcohol 0.9% (bacteriostatic saline) in a 1:1 ratio using aseptic technique at the time of administration. Risks are associated with benzyl alcohol in neonates, infants, pregnant women, and nursing mothers.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Epoetin in adult patients.
### Non–Guideline-Supported Use
- Subcutaneous erythropoietin (average dose: 5227 units/week) and intravenous (IV) iron (average dose: 185 milligrams (mg)/month).[1]
- Epoetin alfa 200 units/kilogram/day for 5 consecutive days per week for up to 7 weeks during radiotherapy.
- Intravenous (IV) erythropoietin (EPO) 300 units/kilogram/day plus IV iron sucrose 200 milligrams (mg)/day on days 1 to 4 postpartum.[2]
- Epoetin alfa (Procrit(R)) 40,000 units subcutaneously once weekly.[3]
- Erythropoietin (150 units/kilogram 3 times/week initially with adjustments every 3 weeks as needed).
- Erythropoietin alfa 150 international units/kilogram subcutaneously 3 times weekly for 26 weeks.[4]
- Subcutaneous erythropoietin 10,000 units 3 days per week.[5]
- 100 units/kilogram (kg) 3 times per week for eight weeks.
- 150 international units/kilogram subcutaneously was administered 3 times per week for at least 12 weeks.[6]
- Epoetin alfa doses of 12,000 to 24,000 units subcutaneously once weekly or 300 to 600 units/kilogram twice weekly.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- Epogen is indicated for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy
- Pediatric Patients (5 to 18 years):
- 600 Units/kg intravenously weekly until completion of a chemotherapy course.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Epoetin in pediatric patients.
### Non–Guideline-Supported Use
- IV erythropoietin dosing was 1250 units/kg/wk as 5 divided doses.
# Contraindications
- Uncontrolled hypertension.
- Pure red cell aplasia (PRCA) that begins after treatment with Epogen or other erythropoietin protein drugs.
- Serious allergic reactions to Epogen.
- Epogen from multidose vials contains benzyl alcohol and is contraindicated in:
- Neonates, infants, pregnant women, and nursing mothers. Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. When therapy with Epogen is needed in neonates and infants, use single-dose vials; do not admix with bacteriostatic saline containing benzyl alcohol.
# Warnings
### Precautions
- In controlled clinical trials of patients with CKD comparing higher hemoglobin targets (13 - 14 g/dL) to lower targets (9 - 11.3 g/dL), Epogen and other ESAs increased the risk of death, myocardial infarction, stroke, congestive heart failure, thrombosis of hemodialysis vascular access, and other thromboembolic events in the higher target groups.
- Using ESAs to target a hemoglobin level of greater than 11 g/dL increases the risk of serious adverse cardiovascular reactions and has not been shown to provide additional benefit. Use caution in patients with coexistent cardiovascular disease and stroke. Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality than other patients. A rate of hemoglobin rise of greater than 1 g/dL over 2 weeks may contribute to these risks.
- In controlled clinical trials of patients with cancer, Epogen and other ESAs increased the risks for death and serious adverse cardiovascular reactions. These adverse reactions included myocardial infarction and stroke.
- In controlled clinical trials, ESAs increased the risk of death in patients undergoing coronary artery bypass graft surgery (CABG) and the risk of deep venous thrombosis (DVT) in patients undergoing orthopedic procedures.
- The design and overall results of the 3 large trials comparing higher and lower hemoglobin targets are shown in Table 1.
- Patients with Chronic Kidney Disease
- Normal Hematocrit Study (NHS)
A prospective, randomized, open-label study of 1265 patients with chronic kidney disease on dialysis with documented evidence of congestive heart failure or ischemic heart disease was designed to test the hypothesis that a higher target hematocrit (Hct) would result in improved outcomes compared with a lower target Hct. In this study, patients were randomized to epoetin alfa treatment targeted to a maintenance hemoglobin of either 14 ± 1 g/dL or 10 ± 1 g/dL. The trial was terminated early with adverse safety findings of higher mortality in the high hematocrit target group. Higher mortality (35% vs. 29%) was observed for the patients randomized to a target hemoglobin of 14 g/dL than for the patients randomized to a target hemoglobin of 10 g/dL. For all-cause mortality, the HR=1.27; 95% CI (1.04, 1.54); p=0.018. The incidence of nonfatal myocardial infarction, vascular access thrombosis, and other thrombotic events was also higher in the group randomized to a target hemoglobin of 14 g/dL.
- A prospective, randomized, open-label study of 1265 patients with chronic kidney disease on dialysis with documented evidence of congestive heart failure or ischemic heart disease was designed to test the hypothesis that a higher target hematocrit (Hct) would result in improved outcomes compared with a lower target Hct. In this study, patients were randomized to epoetin alfa treatment targeted to a maintenance hemoglobin of either 14 ± 1 g/dL or 10 ± 1 g/dL. The trial was terminated early with adverse safety findings of higher mortality in the high hematocrit target group. Higher mortality (35% vs. 29%) was observed for the patients randomized to a target hemoglobin of 14 g/dL than for the patients randomized to a target hemoglobin of 10 g/dL. For all-cause mortality, the HR=1.27; 95% CI (1.04, 1.54); p=0.018. The incidence of nonfatal myocardial infarction, vascular access thrombosis, and other thrombotic events was also higher in the group randomized to a target hemoglobin of 14 g/dL.
- CHOIR
A randomized, prospective trial, 1432 patients with anemia due to CKD who were not undergoing dialysis and who had not previously received epoetin alfa therapy were randomized to epoetin alfa treatment targeting a maintenance hemoglobin concentration of either 13.5 g/dL or 11.3 g/dL. The trial was terminated early with adverse safety findings. A major cardiovascular event (death, myocardial infarction, stroke, or hospitalization for congestive heart failure) occurred in 125 of the 715 patients (18%) in the higher hemoglobin group compared to 97 of the 717 patients (14%) in the lower hemoglobin group [hazard ratio (HR) 1.34, 95% CI: 1.03, 1.74; p = 0.03].
- A randomized, prospective trial, 1432 patients with anemia due to CKD who were not undergoing dialysis and who had not previously received epoetin alfa therapy were randomized to epoetin alfa treatment targeting a maintenance hemoglobin concentration of either 13.5 g/dL or 11.3 g/dL. The trial was terminated early with adverse safety findings. A major cardiovascular event (death, myocardial infarction, stroke, or hospitalization for congestive heart failure) occurred in 125 of the 715 patients (18%) in the higher hemoglobin group compared to 97 of the 717 patients (14%) in the lower hemoglobin group [hazard ratio (HR) 1.34, 95% CI: 1.03, 1.74; p = 0.03].
- TREAT
A randomized, double-blind, placebo-controlled, prospective trial of 4038 patients with: CKD not on dialysis (eGFR of 20 – 60 mL/min), anemia (hemoglobin levels ≤ 11 g/dL), and type 2 diabetes mellitus, patients were randomized to receive either darbepoetin alfa treatment or a matching placebo. Placebo group patients also received darbepoetin alfa when their hemoglobin levels were below 9 g/dL. The trial objectives were to demonstrate the benefit of darbepoetin alfa treatment of the anemia to a target hemoglobin level of 13 g/dL, when compared to a "placebo" group, by reducing the occurrence of either of two primary endpoints: (1) a composite cardiovascular endpoint of all-cause mortality or a specified cardiovascular event (myocardial ischemia, CHF,MI, and CVA) or (2) a composite renal endpoint of all-cause mortality or progression to end stage renal disease. The overall risks for each of the two primary endpoints (the cardiovascular composite and the renal composite) were not reduced with darbepoetin alfa treatment (see Table 1), but the risk of stroke was increased nearly two-fold in the darbepoetin alfa -treated group versus the placebo group: annualized stroke rate 2.1% vs. 1.1%, respectively, HR 1.92; 95% CI: 1.38, 2.68; p < 0.001. The relative risk of stroke was particularly high in patients with a prior stroke: annualized stroke rate 5.2% in the darbepoetin alfa- treated group and 1.9% in the placebo group, HR 3.07; 95% CI: 1.44, 6.54. Also, among darbepoetin alfa -treated subjects with a past history of cancer, there were more deaths due to all causes and more deaths adjudicated as due to cancer, in comparison with the control group.
- A randomized, double-blind, placebo-controlled, prospective trial of 4038 patients with: CKD not on dialysis (eGFR of 20 – 60 mL/min), anemia (hemoglobin levels ≤ 11 g/dL), and type 2 diabetes mellitus, patients were randomized to receive either darbepoetin alfa treatment or a matching placebo. Placebo group patients also received darbepoetin alfa when their hemoglobin levels were below 9 g/dL. The trial objectives were to demonstrate the benefit of darbepoetin alfa treatment of the anemia to a target hemoglobin level of 13 g/dL, when compared to a "placebo" group, by reducing the occurrence of either of two primary endpoints: (1) a composite cardiovascular endpoint of all-cause mortality or a specified cardiovascular event (myocardial ischemia, CHF,MI, and CVA) or (2) a composite renal endpoint of all-cause mortality or progression to end stage renal disease. The overall risks for each of the two primary endpoints (the cardiovascular composite and the renal composite) were not reduced with darbepoetin alfa treatment (see Table 1), but the risk of stroke was increased nearly two-fold in the darbepoetin alfa -treated group versus the placebo group: annualized stroke rate 2.1% vs. 1.1%, respectively, HR 1.92; 95% CI: 1.38, 2.68; p < 0.001. The relative risk of stroke was particularly high in patients with a prior stroke: annualized stroke rate 5.2% in the darbepoetin alfa- treated group and 1.9% in the placebo group, HR 3.07; 95% CI: 1.44, 6.54. Also, among darbepoetin alfa -treated subjects with a past history of cancer, there were more deaths due to all causes and more deaths adjudicated as due to cancer, in comparison with the control group.
- Patients with Cancer
- An increased incidence of thromboembolic reactions, some serious and life-threatening, occurred in patients with cancer treated with ESAs.
- In a randomized, placebo-controlled study (Study 1 in Table 2) of 939 women with metastatic breast cancer receiving chemotherapy, patients received either weekly epoetin alfa or placebo for up to a year. This study was designed to show that survival was superior when epoetin alfa was administered to prevent anemia (maintain hemoglobin levels between 12 and 14 g/dL or hematocrit between 36% and 42%). This study was terminated prematurely when interim results demonstrated a higher mortality at 4 months (8.7% vs. 3.4%) and a higher rate of fatal thrombotic reactions (1.1% vs. 0.2%) in the first 4 months of the study among patients treated with epoetin alfa. Based on Kaplan-Meier estimates, at the time of study termination, the 12-month survival was lower in the epoetin alfa group than in the placebo group (70% vs. 76%; HR 1.37, 95% CI: 1.07, 1.75; p = 0.012).
- Patients Having Surgery
- An increased incidence of deep venous thrombosis (DVT) in patients receiving epoetin alfa undergoing surgical orthopedic procedures was demonstrated. In a randomized, controlled study, 680 adult patients, not receiving prophylactic anticoagulation and undergoing spinal surgery, were randomized to 4 doses of 600 Units/kg epoetin alfa (7, 14, and 21 days before surgery, and the day of surgery) and standard of care (SOC) treatment (n = 340) or to SOC treatment alone (n = 340). A higher incidence of DVTs, determined by either color flow duplex imaging or by clinical symptoms, was observed in the epoetin alfa group (16 [4.7%] patients) compared with the SOC group (7 [2.1%] patients). In addition to the 23 patients with DVTs included in the primary analysis, 19 [2.8%] patients (n = 680) experienced 1 other thrombovascular event (TVE) each (12 [3.5%] in the epoetin alfa group and 7 [2.1%] in the SOC group). Deep venous thrombosis prophylaxis is strongly recommended when ESAs are used for the reduction of allogeneic RBC transfusions in surgical patients.
- Increased mortality was observed in a randomized, placebo-controlled study of Epogen in adult patients who were undergoing CABG surgery (7 deaths in 126 patients randomized to Epogen versus no deaths among 56 patients receiving placebo). Four of these deaths occurred during the period of study drug administration and all 4 deaths were associated with thrombotic events.
- In order to prescribe and/or dispense Epogen to patients with cancer and anemia due to myelosuppressive chemotherapy, prescribers and hospitals must enroll in and comply with the ESA APPRISE Oncology Program requirements. To enroll, visit www.esa-apprise.com or call 1-866-284-8089 for further assistance. Additionally, prior to each new course of Epogen in patients with cancer, prescribers and patients must provide written acknowledgment of a discussion of the risks of Epogen.
- ESAs resulted in decreased locoregional control/progression-free survival and/or overall survival (see Table 2). These findings were observed in studies of patients with advanced head and neck cancer receiving radiation therapy (Studies 5 and 6), in patients receiving chemotherapy for metastatic breast cancer (Study 1) or lymphoid malignancy (Study 2), and in patients with non-small cell lung cancer or various malignancies who were not receiving chemotherapy or radiotherapy (Studies 7 and 8).
- Decreased Overall Survival
- Study 1 was described in the previous section. Mortality at 4 months (8.7% vs. 3.4%) was significantly higher in the epoetin alfa arm. The most common investigator-attributed cause of death within the first 4 months was disease progression; 28 of 41 deaths in the epoetin alfa arm and 13 of 16 deaths in the placebo arm were attributed to disease progression. Investigator-assessed time to tumor progression was not different between the 2 groups. Survival at 12 months was significantly lower in the epoetin alfa arm (70% vs. 76%; HR 1.37, 95% CI: 1.07, 1.75; p = 0.012).
- Study 2 was a randomized, double-blind study (darbepoetin alfa vs. placebo) conducted in 344 anemic patients with lymphoid malignancy receiving chemotherapy. With a median follow-up of 29 months, overall mortality rates were significantly higher among patients randomized to darbepoetin alfa as compared to placebo (HR 1.36, 95% CI: 1.02, 1.82).
- Study 7 was a multicenter, randomized, double-blind study (epoetin alfa vs. placebo) in which patients with advanced non-small cell lung cancer receiving only palliative radiotherapy or no active therapy were treated with epoetin alfa to achieve and maintain hemoglobin levels between 12 and 14 g/dL. Following an interim analysis of 70 patients (planned accrual 300 patients), a significant difference in survival in favor of the patients in the placebo arm of the study was observed (median survival 63 vs. 129 days; HR 1.84; p = 0.04).
- Study 8 was a randomized, double-blind study (darbepoetin alfa vs. placebo) in 989 anemic patients with active malignant disease, neither receiving nor planning to receive chemotherapy or radiation therapy. There was no evidence of a statistically significant reduction in proportion of patients receiving RBC transfusions. The median survival was shorter in the darbepoetin alfa treatment group than in the placebo group (8 months vs. 10.8 months; HR 1.30, 95% CI: 1.07, 1.57).
- Decreased Progression-free Survival and Overall Survival
- Study 3 was a randomized, open-label, controlled, factorial design study in which darbepoetin alfa was administered to prevent anemia in 733 women receiving neo-adjuvant breast cancer treatment. A final analysis was performed after a median follow-up of approximately 3 years. The 3-year survival rate was lower (86% vs. 90%; HR 1.42, 95% CI: 0.93, 2.18) and the 3-year relapse-free survival rate was lower (72% vs. 78%; HR 1.33, 95% CI: 0.99, 1.79) in the darbepoetin alfa-treated arm compared to the control arm.
- Study 4 was a randomized, open-label, controlled study that enrolled 114 of a planned 460 cervical cancer patients receiving chemotherapy and radiotherapy. Patients were randomized to receive epoetin alfa to maintain hemoglobin between 12 and 14 g/dL or to RBC transfusion support as needed. The study was terminated prematurely due to an increase in thromboembolic adverse reactions in epoetin alfa-treated patients compared to control (19% vs. 9%). Both local recurrence (21% vs. 20%) and distant recurrence (12% vs. 7%) were more frequent in epoetin alfa-treated patients compared to control. Progression-free survival at 3 years was lower in the epoetin alfa-treated group compared to control (59% vs. 62%; HR 1.06, 95% CI: 0.58, 1.91). Overall survival at 3 years was lower in the epoetin alfa-treated group compared to control (61% vs. 71%; HR 1.28, 95% CI: 0.68, 2.42).
- Study 5 was a randomized, placebo-controlled study in 351 head and neck cancer patients where epoetin beta or placebo was administered to achieve target hemoglobins ≥ 14 and ≥ 15 g/dL for women and men, respectively. Locoregional progression-free survival was significantly shorter in patients receiving epoetin beta (HR 1.62, 95% CI: 1.22, 2.14; p = 0.0008) with medians of 406 days and 745 days in the epoetin beta and placebo arms, respectively. Overall survival was significantly shorter in patients receiving epoetin beta (HR 1.39, 95% CI: 1.05, 1.84; p = 0.02).
- Decreased Locoregional Control
- Study 6 was a randomized, open-label, controlled study conducted in 522 patients with primary squamous cell carcinoma of the head and neck receiving radiation therapy alone (no chemotherapy) who were randomized to receive darbepoetin alfa to maintain hemoglobin levels of 14 to15.5 g/dL or no darbepoetin alfa. An interim analysis performed on 484 patients demonstrated that locoregional control at 5 years was significantly shorter in patients receiving darbepoetin alfa (RR 1.44, 95% CI: 1.06, 1.96; p = 0.02). Overall survival was shorter in patients receiving darbepoetin alfa (RR 1.28, 95% CI: 0.98, 1.68; p = 0.08).
- Epogen is contraindicated in patients with uncontrolled hypertension. Following initiation and titration of Epogen, approximately 25% of patients on dialysis required initiation of or increases in antihypertensive therapy; hypertensive encephalopathy and seizures have been reported in patients with CKD receiving Epogen.
- Appropriately control hypertension prior to initiation of and during treatment with Epogen. Reduce or withhold Epogen if blood pressure becomes difficult to control. Advise patients of the importance of compliance with antihypertensive therapy and dietary restrictions.
- Epogen increases the risk of seizures in patients with CKD. During the first several months following initiation of Epogen, monitor patients closely for premonitory neurologic symptoms. Advise patients to contact their healthcare practitioner for new-onset seizures, premonitory symptoms or change in seizure frequency.
- For lack or loss of hemoglobin response to Epogen, initiate a search for causative factors (e.g., iron deficiency, infection, inflammation, bleeding). If typical causes of lack or loss of hemoglobin response are excluded, evaluate for PRCA. In the absence of PRCA, follow dosing recommendations for management of patients with an insufficient hemoglobin response to Epogen therapy.
- Cases of PRCA and of severe anemia, with or without other cytopenias that arise following the development of neutralizing antibodies to erythropoietin have been reported in patients treated with Epogen. This has been reported predominantly in patients with CKD receiving ESAs by subcutaneous administration. PRCA has also been reported in patients receiving ESAs for anemia related to hepatitis C treatment (an indication for which Epogen is not approved).
- If severe anemia and low reticulocyte count develop during treatment with Epogen, withhold Epogen and evaluate patients for neutralizing antibodies to erythropoietin. Contact Amgen (1-800-77-AMGEN) to perform assays for binding and neutralizing antibodies. Permanently discontinue Epogen in patients who develop PRCA following treatment with Epogen or other erythropoietin protein drugs. Do not switch patients to other ESAs.
- Serious allergic reactions, including anaphylactic reactions, angioedema, bronchospasm, skin rash, and urticaria may occur with Epogen. Immediately and permanently discontinue Epogen and administer appropriate therapy if a serious allergic or anaphylactic reaction occurs.
- Epogen contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.
- Patients may require adjustments in their dialysis prescriptions after initiation of Epogen. Patients receiving Epogen may require increased anticoagulation with heparin to prevent clotting of the extracorporeal circuit during hemodialysis.
- Evaluate transferrin saturation and serum ferritin prior to and during Epogen treatment. Administer supplemental iron therapy when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20%. The majority of patients with CKD will require supplemental iron during the course of ESA therapy. Following initiation of therapy and after each dose adjustment, monitor hemoglobin weekly until the hemoglobin level is stable and sufficient to minimize the need for RBC transfusion.
# Adverse Reactions
## Clinical Trials Experience
- Increased Mortality, Myocardial Infarction, Stroke, and Thromboembolism
- Increased mortality and/or increased risk of tumor progression or recurrence in Patients With Cancer
- Hypertension
- Seizures
- PRCA
- Serious allergic reactions.
- Adult Patients
- Three double-blind, placebo-controlled studies, including 244 patients with CKD on dialysis, were used to identify the adverse reactions to Epogen. In these studies, the mean age of patients was 48 years (range: 20 to 80 years). One hundred and thirty-three (55%) patients were men. The racial distribution was as follows: 177 (73%) patients were white, 48 (20%) patients were black, 4 (2%) patients were Asian, 12 (5%) patients were other, and racial information was missing for 3 (1%) patients.
- Two double-blind, placebo-controlled studies, including 210 patients with CKD not on dialysis, were used to identify the adverse reactions to Epogen. In these studies, the mean age of patients was 57 years (range: 24 to 79 years). One hundred and twenty-one (58%) patients were men. The racial distribution was as follows: 164 (78%) patients were white, 38 (18%) patients were black, 3 (1%) patients were Asian, 3 (1%) patients were other, and racial information was missing for 2 (1%) patients.
- The adverse reactions with a reported incidence of ≥ 5% in Epogen-treated patients and that occurred at a ≥ 1% higher frequency than in placebo-treated patients are shown in the table below:
- An additional serious adverse reaction that occurred in less than 5% of epoetin alfa-treated dialysis patients and greater than placebo was thrombosis (2.7% Epogen and 1% placebo).
- The adverse reactions with a reported incidence of ≥ 5% in Epogen-treated patients and that occurred at a ≥ 1% higher frequency than in placebo-treated patients are shown in the table below:
- Additional serious adverse reactions that occurred in less than 5% of epoetin alfa-treated patients not on dialysis and greater than placebo were erythema (0.8% Epogen and 0% placebo) and myocardial infarction (0.8% Epogen and 0% placebo).
- Pediatric Patients
- In pediatric patients with CKD on dialysis, the pattern of adverse reactions was similar to that found in adults.
- A total of 297 zidovudine-treated HIV-infected patients were studied in 4 placebo-controlled studies. A total of 144 (48%) patients were randomly assigned to receive Epogen and 153 (52%) patients were randomly assigned to receive placebo. Epogen was administered at doses between 100 and 200 Units/kg 3 times weekly subcutaneously for up to 12 weeks.
- For the combined Epogen treatment groups, a total of 141 (98%) men and 3 (2%) women between the ages of 24 and 64 years were enrolled. The racial distribution of the combined Epogen treatment groups was as follows: 129 (90%) white, 8 (6%) black, 1 (1%) Asian, and 6 (4%) other.
- In double-blind, placebo-controlled studies of 3 months duration involving approximately 300 zidovudine-treated HIV-infected patients, adverse reactions with an incidence of ≥ 1% in patients treated with Epogen were:
- The data below were obtained in Study C1, a 16-week, double-blind, placebo-controlled study that enrolled 344 patients with anemia secondary to chemotherapy. There were 333 patients who were evaluable for safety; 168 of 174 patients (97%) randomized to Epogen received at least 1 dose of study drug, and 165 of 170 patients (97%) randomized to placebo received at least 1 placebo dose. For the once weekly Epogen-treatment group, a total of 76 men (45%) and 92 women (55%) between the ages of 20 and 88 years were treated. The racial distribution of the Epogen-treatment group was 158 white (94%) and 10 black (6%). Epogen was administered once weekly for an average of 13 weeks at a dose of 20,000 to 60,000 IU subcutaneously (mean weekly dose was 49,000 IU).
- The adverse reactions with a reported incidence of ≥ 5% in Epogen-treated patients that occurred at a higher frequency than in placebo-treated patients are shown in the table below:
- Four hundred sixty-one patients undergoing major orthopedic surgery were studied in a placebo-controlled study (S1) and a comparative dosing study (2 dosing regimens, S2). A total of 358 patients were randomly assigned to receive Epogen and 103 (22%) patients were randomly assigned to receive placebo. Epogen was administered daily at a dose of 100 to 300 IU/kg subcutaneously for 15 days or at 600 IU/kg once weekly for 4 weeks.
- For the combined Epogen treatment groups, a total of 90 (25%) and 268 (75%) women between the ages of 29 and 89 years were enrolled. The racial distribution of the combined Epogen treatment groups was as follows: 288 (80%) white, 64 (18%) black, 1 (< 1%) Asian, and 5 (1%) other.
- The adverse reactions with a reported incidence of ≥ 1% in Epogen-treated patients that occurred at a higher frequency than in placebo-treated patients are shown in the table below:
## Postmarketing Experience
- Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- The following adverse reactions have been identified during postmarketing use of Epogen:
- Seizures
- PRCA
- Serious allergic reactions
- Injection site reactions, including irritation and pain
- Porphyria
# Drug Interactions
- No formal drug interaction studies have been conducted with Epogen.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
- Pregnancy Category C
- There are no adequate and well-controlled studies of Epogen use during pregnancy. There are limited data on Epogen use in pregnant women. In animal reproductive and developmental toxicity studies, adverse fetal effects occurred when pregnant rats received epoetin alfa at doses approximating the clinical recommended starting doses. Single-dose formulations of Epogen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- There are reports of at least 33 pregnant women with anemia alone or anemia associated with severe renal disease and other hematologic disorders who received Epogen. Polyhydramnios and intrauterine growth restriction were reported in women with chronic renal disease, which is associated with an increased risk for these adverse pregnancy outcomes. There was 1 infant born with pectus excavatum and hypospadias following exposure during the first trimester. Due to the limited number of exposed pregnancies and multiple confounding factors (such as underlying maternal conditions, other maternal medications, and gestational timing of exposure), these published case reports and studies do not reliably estimate the frequency or absence of adverse outcomes.
- When healthy rats received Epogen at doses of 100 Units/kg/day during mating and through early pregnancy (dosing stopped prior to organogenesis), there were slight increases in the incidences of pre-and post-implantation loss, and a decrease in live fetuses. This animal dose level of 100 Units/kg/day may approximate the clinical recommended starting dose, depending on the treatment indication. When healthy pregnant rats and rabbits received intravenous doses of up to 500 mg/kg/day of Epogen only during organogenesis, no teratogenic effects were observed in the offspring.
- When healthy pregnant rats received Epogen at doses of 500 Units/kg/day late in pregnancy (after the period of organogenesis), offspring had decreased number of caudal vertebrae and growth delays.
- Women who become pregnant during Epogen treatment are encouraged to enroll in Amgen’s Pregnancy Surveillance Program. Patients or their physicians should call 1-800-772-6436 (1-800-77-AMGEN) to enroll.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Epoetin in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Epoetin during labor and delivery.
### Nursing Mothers
- The multidose vials of Epogen are formulated with benzyl alcohol. Do not administer Epogen from multidose vials, or Epogen from single-dose vials admixed with bacteriostatic saline containing benzyl alcohol, to a nursing woman. When therapy with Epogen is needed in nursing women, use a benzyl alcohol-free formulation.
- It is not known whether Epogen is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Epogen from single-dose vials is administered to a nursing woman.
### Pediatric Use
- The multidose vials are formulated with benzyl alcohol. Do not administer Epogen from multidose vials, or Epogen from single-dose vials admixed with bacteriostatic saline containing benzyl alcohol, to neonates or infants. When therapy with Epogen is needed in neonates and infants, use a benzyl alcohol-free formulation.
- Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. The "gasping syndrome," (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages > 99 mg/kg/day in neonates and low-birthweight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse.
- Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the "gasping syndrome", the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birthweight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.
- Pediatric Patients on Dialysis
- Epogen is indicated in pediatric patients, ages 1 month to 16 years of age, for the treatment of anemia associated with CKD requiring dialysis. Safety and effectiveness in pediatric patients less than 1 month old have not been established.
- The safety data from these studies are similar to those obtained from the studies of Epogen in adult patients with CKD.
- Pediatric Cancer Patients on Chemotherapy
- Epogen is indicated in patients 5 to 18 years old for the treatment of anemia due to concomitant myelosuppressive chemotherapy. Safety and effectiveness in pediatric patients less than 5 years of age have not been established. The safety data from these studies are similar to those obtained from the studies of Epogen in adult patients with cancer.
- Pediatric Patients With HIV Infection Receiving Zidovudine
- Published literature has reported the use of Epogen in 20 zidovudine-treated, anemic, pediatric patients with HIV infection, ages 8 months to 17 years, treated with 50 to 400 Units/kg subcutaneously or intravenously 2 to 3 times per week. Increases in hemoglobin levels and in reticulocyte counts and decreases in or elimination of RBC transfusions were observed.
- Pharmacokinetics in Neonates
- Limited pharmacokinetic data from a study of 7 preterm, very low birth weight neonates and 10 healthy adults given intravenous erythropoietin suggested that distribution volume was approximately 1.5 to 2 times higher in the preterm neonates than in the healthy adults, and clearance was approximately 3 times higher in the preterm neonates than in the healthy adults.
### Geriatic Use
- Of the 4553 patients who received Epogen in the 6 studies for treatment of anemia due to CKD not receiving dialysis, 2726 (60%) were age 65 years and over, while 1418 (31%) were 75 years and over. Of the 757 patients who received Epogen in the 3 studies of CKD patients on dialysis, 361 (47%) were age 65 years and over, while 100 (13%) were 75 years and over. No differences in safety or effectiveness were observed between geriatric and younger patients. Dose selection and adjustment for an elderly patient should be individualized to achieve and maintain the target hemoglobin.
- Among 778 patients enrolled in the 3 clinical studies of Epogen for the treatment of anemia due to concomitant chemotherapy, 419 received Epogen and 359 received placebo. Of the 419 who received Epogen, 247 (59%) were age 65 years and over, while 78 (19%) were 75 years and over. No overall differences in safety or effectiveness were observed between geriatric and younger patients. The dose requirements for Epogen in geriatric and younger patients within the 3 studies were similar.
- Among 1731 patients enrolled in the 6 clinical studies of Epogen for reduction of allogeneic RBC transfusions in patients undergoing elective surgery, 1085 received Epogen and 646 received placebo or standard of care treatment. Of the 1085 patients who received Epogen, 582 (54%) were age 65 years and over, while 245 (23%) were 75 years and over. No overall differences in safety or effectiveness were observed between geriatric and younger patients. The dose requirements for Epogen in geriatric and younger patients within the 4 studies using the 3 times weekly schedule and 2 studies using the weekly schedule were similar.
- Insufficient numbers of patients age 65 years or older were enrolled in clinical studies of Epogen for the treatment of zidovudine in HIV-infected patients to determine whether they respond differently from younger patients.
### Gender
There is no FDA guidance on the use of Epoetin with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Epoetin with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Epoetin in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Epoetin in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Epoetin in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Epoetin in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Subcutaneous
- Intravenous
### Monitoring
- To undergo regular blood pressure monitoring.
- Evaluate transferrin saturation and serum ferritin prior to and during Epogen treatment.
- Epogen increases the risk for seizures in patients with CKD. Increase monitoring of these patients for changes in seizure frequency or premonitory symptoms
# IV Compatibility
There is limited information regarding IV Compatibility of Epoetin in the drug label.
# Overdosage
- Epogen overdosage can cause hemoglobin levels above the desired level, which should be managed with discontinuation or reduction of Epogen dosage and/or with phlebotomy as clinically indicated.
- Cases of severe hypertension have been observed following overdose with ESAs
## Chronic Overdose
There is limited information regarding Chronic Overdose of Epoetin in the drug label.
# Pharmacology
## Mechanism of Action
- Epogen stimulates erythropoiesis by the same mechanism as endogenous erythropoietin.
## Structure
- Epogen (epoetin alfa) is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin.
- Epogen is formulated as a sterile, colorless liquid in vials in multiple formulations. Single-dose vials, formulated with an isotonic sodium chloride/sodium citrate-buffered solution, are supplied in multiple strengths. Each 1 mL vial contains 2000, 3000, 4000, or 10,000 Units of epoetin alfa, Albumin (Human) (2.5 mg), citric acid (0.06 mg), sodium chloride (5.9 mg), and sodium citrate (5.8 mg) in Water for Injection, USP (pH 6.9 ± 0.3). Single-dose 1 mL vials formulated with an isotonic sodium chloride/sodium phosphate buffer contain 40,000 Units of epoetin alfa albumin (human) (2.5 mg), citric acid (0.0068 mg), sodium chloride (5.8 mg), sodium citrate (0.7 mg), sodium phosphate dibasic anhydrate (1.8 mg), and sodium phosphate monobasic monohydrate (1.2 mg) in Water for Injection, USP (pH 6.9 ± 0.3). Multidose, 2 mL vials contain 10,000 Units epoetin alfa, albumin (human) (2.5 mg), benzyl alcohol (1%), sodium chloride (8.2 mg), and sodium citrate (1.3 mg) per 1 mL Water for Injection, USP (pH 6.1 ± 0.3). Multidose 1 mL vials contain 20,000 Units epoetin alfa, albumin (human) (2.5 mg), benzyl alcohol (1%), sodium chloride (8.2 mg), citric acid (0.11 mg), and sodium citrate (1.3 mg), per 1 mL in Water for Injection, USP (pH 6.1 ± 0.3).
## Pharmacodynamics
- Epogen increases the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks. The rate of hemoglobin increase varies among patients and is dependent upon the dose of Epogen administered. For correction of anemia in hemodialysis patients, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly.
## Pharmacokinetics
- In adult and pediatric patients with CKD, the elimination half-life (t1/2) of plasma erythropoietin after intravenous administration of Epogen ranged from 4 to 13 hours. After subcutaneous administration, Cmax was achieved within 5 to 24 hours. The t1/2 in adult patients with serum creatinine greater than 3 mg/dL was similar between those not on dialysis and those maintained on dialysis. The pharmacokinetic data indicate no apparent difference in Epogen t1/2 among adult patients above or below 65 years of age.
- A pharmacokinetic study comparing 150 Units/kg subcutaneous 3 times weekly to 40,000 Units subcutaneous weekly dosing regimen was conducted for 4 weeks in healthy subjects (n = 12) and for 6 weeks in anemic cancer patients (n = 32) receiving cyclic chemotherapy. There was no accumulation of serum erythropoietin after the 2 dosing regimens during the study period. The 40,000 Units weekly regimen had a higher Cmax (3- to 7-fold), longer Tmax (2- to 3-fold), higher AUC0-168 h (2- to 3-fold) of erythropoietin and lower clearance (CL) (50%) than the 150 Units/kg 3 times weekly regimen. In anemic cancer patients, the average t1/2 was similar (40 hours with range of 16 to 67 hours) after both dosing regimens. After the 150 Units/kg 3 times weekly dosing, the values of Tmax and CL were similar (13.3 ± 12.4 vs. 14.2 ± 6.7 hours, and 20.2 ± 15.9 vs. 23.6 ± 9.5 mL/hr/kg) between week 1 when patients were receiving chemotherapy (n = 14) and week 3 when patients were not receiving chemotherapy (n = 4). Differences were observed after the 40,000 Units weekly dosing with longer Tmax (38 ± 18 hours) and lower CL (9.2 ± 4.7 mL/hr/kg) during week 1 when patients were receiving chemotherapy (n = 18) compared with those (22 ± 4.5 hours, 13.9 ± 7.6 mL/hr/kg, respectively) during week 3 when patients were not receiving chemotherapy (n = 7).
- The pharmacokinetic profile of Epogen in children and adolescents appeared similar to that of adults.
- The pharmacokinetics of Epogen has not been studied in patients with HIV infection.
## Nonclinical Toxicology
- Carcinogenicity
- The carcinogenic potential of Epogen has not been evaluated.
- Mutagenicity
- Epogen was not mutagenic or clastogenic under the conditions tested: Epogen was negative in the in vitro bacterial reverse mutation assay (Ames test), in the in vitro mammalian cell gene mutation assay (the hypoxanthine-guanine phosphoribosyl transferase [HGPRT] locus), in an in vitro chromosomal aberration assay in mammalian cells, and in the in vivo mouse micronucleus assay.
- Impairment of Fertility
- When administered intravenously to male and female rats prior to and during mating, and to females through the beginning of implantation (up to gestational day 7; dosing stopped prior to the beginning of organogenesis), doses of 100 and 500 Units/kg/day of Epogen caused slight increases in pre-implantation loss, post-implantation loss and decreases in the incidence of live fetuses. It is not clear whether these effects reflect a drug effect on the uterine environment or on the conceptus. This animal dose level of 100 Units/kg/day approximates the clinical recommended starting dose, depending on the patient’s treatment indication, but may be lower than the clinical dose in patients whose doses have been adjusted.
- When pregnant rats were administered intravenous Epogen, 500 Units/kg/day, after the period of organogenesis (from day 17 of gestation through day 21 of lactation), their pups exhibited decreased number of caudal vertebrae, decreased body weight gain, and delayed appearance of abdominal hair, eyelid opening, and ossification. This animal dose level of 500 Units/kg/day is approximately 5-fold higher than the clinical recommended starting dose, depending on the patient’s treatment indication.
- When Epogen was administered intravenously during the period of organogenesis to pregnant rats (gestational days 7 to 17) and pregnant rabbits (gestational days 6 to 18), no evidence of teratogenic outcome was observed at the doses tested, up to 500 Units/kg/day. The offspring (F1 generation) of the treated rats were observed postnatally; rats from the F1 generation reached maturity and were mated; no Epogen-related effects were apparent for their offspring (F2 generation fetuses).
# Clinical Studies
- Adult Patients on Dialysis
- Patients with chronic kidney disease on dialysis: ESA effects on rates of transfusion
- In clinical studies of CKD patients on dialysis, Epogen increased hemoglobin levels and decreased the need for RBC transfusion. Overall, more than 95% of patients were RBC transfusion-independent after receiving Epogen for 3 months. In clinical studies at starting doses of 50 to 150 Units/kg 3 times weekly, adult patients responded with an average rate of hemoglobin rise as presented in Table 8.
- The safety and efficacy of Epogen were evaluated in 13 clinical studies involving intravenous administration to a total of 1010 anemic patients on dialysis. Overall, more than 90% of the patients treated with Epogen experienced improvement in hemoglobin concentrations. In the 3 largest of these clinical studies, the median maintenance dose necessary to maintain the hemoglobin between 10 to 12 g/dL was approximately 75 Units/kg 3 times weekly. More than 95% of patients were able to avoid RBC transfusions. In the largest US multicenter study, approximately 65% of the patients received doses of 100 Units/kg 3 times weekly or less to maintain their hemoglobin at approximately 11.7 g/dL. Almost 10% of patients received a dose of 25 Units/kg or less, and approximately 10% received a dose of more than 200 Units/kg 3 times weekly to maintain their hemoglobin at this level.
- In the Normal Hematocrit Study, the yearly transfusion rate was 51.5% in the lower hemoglobin group (10 g/dL) and 32.4% in the higher hemoglobin group (14 g/dL).
- Other ESA trials
- In a 26-week, double-blind, placebo-controlled study, 118 patients on dialysis with an average hemoglobin of approximately 7 g/dL were randomized to either Epogen or placebo. By the end of the study, average hemoglobin increased to approximately 11 g/dL in the Epogen-treated patients and remained unchanged in patients receiving placebo. Epogen-treated patients experienced improvements in exercise tolerance and patient-reported physical functioning at month 2 that were maintained throughout the study.
- A multicenter, unit-dose study was also conducted in 119 patients receiving peritoneal dialysis who self-administered Epogen subcutaneously. Patients responded to Epogen administered subcutaneously in a manner similar to patients receiving intravenous administration.
- The safety and efficacy of Epogen were studied in a placebo-controlled, randomized study of 113 children with anemia (hemoglobin ≤ 9 g/dL) undergoing peritoneal dialysis or hemodialysis. The initial dose of Epogen was 50 Units/kg intravenously or subcutaneously 3 times weekly. The dose of study drug was titrated to achieve either a hemoglobin of 10 to 12 g/dL or an absolute increase in hemoglobin of 2 g/dL over baseline.
- At the end of the initial 12 weeks, a statistically significant rise in mean hemoglobin (3.1 g/dL vs. 0.3 g/dL) was observed only in the Epogen arm. The proportion of children achieving a hemoglobin of 10 g/dL, or an increase in hemoglobin of 2 g/dL over baseline, at any time during the first 12 weeks was higher in the Epogen arm (96% vs. 58%). Within 12 weeks of initiating Epogen therapy, 92.3% of the pediatric patients were RBC transfusion independent as compared to 65.4% who received placebo. Among patients who received 36 weeks of Epogen, hemodialysis patients received a higher median maintenance dose [167 Units/kg/week (n = 28) vs. 76 Units/kg/week (n = 36)] and took longer to achieve a hemoglobin of 10 to 12 g/dL (median time to response 69 days vs. 32 days) than patients undergoing peritoneal dialysis.
- Four clinical studies were conducted in patients with CKD not on dialysis involving 181 patients treated with Epogen. These patients responded to Epogen therapy in a manner similar to that observed in patients on dialysis. Patients with CKD not on dialysis demonstrated a dose-dependent and sustained increase in hemoglobin when Epogen was administered by either an intravenous or subcutaneous route, with similar rates of rise of hemoglobin when Epogen was administered by either route.
- In TREAT, a randomized, double-blind trial of 4038 patients with CKD and type 2 diabetes not on dialysis, a post-hoc analysis showed that the proportion of patients receiving RBC transfusions was lower in patients administered an ESA to target a hemoglobin of 13 g/dL compared to the control arm in which an ESA was administered intermittently if hemoglobin concentration decreased to less than 9 g/dL (15% versus 25%, respectively). In CHOIR, a randomized open-label study of 1432 patients with CKD not on dialysis, use of epoetin alfa to target a higher (13.5 g/dL) versus lower (11.3 g/dL) hemoglobin goal did not reduce the use of RBC transfusions. In each trial, no benefits occurred for the cardiovascular or end-stage renal disease outcomes. In each trial, the potential benefit of ESA therapy was offset by worse cardiovascular safety outcomes resulting in an unfavorable benefit-risk profile.
- ESA Effects on rates of death and other serious cardiac adverse events
- Three randomized outcome trials (Normal Hematocrit Study [NHS], Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease [CHOIR], and Trial of Darbepoetin Alfa in Type 2 Diabetes and CKD [TREAT]) have been conducted in patients with CKD using Epogen/PROCRIT/Aranesp to target higher vs. lower hemoglobin levels. Though these trials were designed to establish a cardiovascular or renal benefit of targeting higher hemoglobin levels, in all 3 studies, patients randomized to the higher hemoglobin target experienced worse cardiovascular outcomes and showed no reduction in progression to ESRD. In each trial, the potential benefit of ESA therapy was offset by worse cardiovascular safety outcomes resulting in an unfavorable benefit-risk profile.
- The safety and efficacy of Epogen were evaluated in 4 placebo-controlled studies enrolling 297 anemic patients (hemoglobin < 10 g/dL) with HIV infection receiving concomitant therapy with zidovudine. In the subgroup of patients (89/125 Epogen and 88/130 placebo) with pre study endogenous serum erythropoietin levels ≤ 500 mUnits/mL, Epogen reduced the mean cumulative number of units of blood transfused per patient by approximately 40% as compared to the placebo group. Among those patients who required RBC transfusions at baseline, 43% of patients treated with Epogen versus 18% of placebo-treated patients were RBC transfusion independent during the second and third months of therapy. Epogen therapy also resulted in significant increases in hemoglobin in comparison to placebo. When examining the results according to the weekly dose of zidovudine received during month 3 of therapy, there was a statistically significant reduction (p < 0.003) in RBC transfusion requirements in patients treated with Epogen (n = 51) compared to placebo-treated patients (n = 54) whose mean weekly zidovudine dose was ≤ 4200 mg/week.
- Approximately 17% of the patients with endogenous serum erythropoietin levels ≤ 500 mUnits/mL receiving Epogen in doses from 100 to 200 Units/kg 3 times weekly achieved a hemoglobin of 12.7 g/dL without administration of RBC transfusions or significant reduction in zidovudine dose. In the subgroup of patients whose pre study endogenous serum erythropoietin levels were > 500 mUnits/mL, Epogen therapy did not reduce RBC transfusion requirements or increase hemoglobin compared to the corresponding responses in placebo-treated patients.
- The safety and effectiveness of Epogen was assessed in two multicenter, randomized (1:1), placebo-controlled, double-blind studies (Study C1 and Study C2) and a pooled analysis of six additional randomized (1:1), multicenter, placebo-controlled, double-blind studies. All studies were conducted in patients with anemia due to concomitantly administered cancer chemotherapy. Study C1 enrolled 344 adult patients, Study C2 enrolled 222 pediatric patients, and the pooled analysis contained 131 patients randomized to epoetin alfa or placebo. In Studies C1 and C2, efficacy was demonstrated by a reduction in the proportion of patients who received an RBC transfusion, from week 5 through end of the study, with the last-known RBC transfusion status carried forward for patients who discontinued treatment. In the pooled analysis, efficacy was demonstrated by a reduction in the proportion of patients who received an RBC transfusion from week 5 through end of the study in the subset of patients who were remaining on therapy for 6 or more weeks.
- Study C1
- Study C1 was conducted in anemic patients (hemoglobin < 11.5 g/dL for males; < 10.5 g/dL for females) with non-myeloid malignancies receiving myelosuppressive chemotherapy. Randomization was stratified by type of malignancy (lung vs. breast vs. other), concurrent radiation therapy planned (yes or no), and baseline hemoglobin (< 9 g/dL vs. ≥ 9 g/dL); patients were randomized to epoetin alfa 40,000 Units (n = 174) or placebo (n = 170) as a weekly subcutaneous injection commencing on the first day of the chemotherapy cycle.
- Ninety-one percent of patients were white, 44% were male, and the median age of patients was 66 years (range: 20 to 88 years). The proportion of patients withdrawn from the study prior to week 5 was less than 10% for placebo-treated or epoetin-treated patients. Per protocol, the last available hemoglobin values from patients who dropped out were included in the efficacy analyses. Efficacy results are shown in Table 9.
- Study C2
- Study C2 was conducted in 222 anemic patients, ages 5 to 18, receiving chemotherapy for the treatment of various childhood malignancies. Randomization was stratified by cancer type (solid tumors, Hodgkin’s disease, acute lymphocytic leukemia, vs. non-Hodgkin’s lymphoma); patients were randomized to receive epoetin alfa at 600 Units/kg maximum 40,000 Units (n = 111) or placebo (n = 111) as a weekly intravenous injection.
- Sixty-nine percent of patients were white, 55% were male, and the median age of patients was 12 years (range: 5 to 18 years). Two (2%) of placebo-treated patients and 3 (3%) of epoetin alfa-treated patients dropped out of the study prior to week 5. There were fewer RBC transfusions from week 5 through the end-of-study in epoetin-alfa treated patients [51% (57/111)] compared to placebo-treated patients [69% (77/111)]. There was no evidence of an improvement in health-related quality of life, including no evidence of an effect on fatigue, energy, or strength in patients receiving Epogen as compared to those receiving placebo.
- Pooled Analysis (Three Times Per Week Dosing)
- The results of 6 studies of similar design and that randomized 131 patients to epoetin alfa or placebo were pooled to assess the safety and effectiveness of epoetin alfa. Patients were randomized to receive epoetin alfa at 150 Units/kg (n = 63) or placebo (n = 68), subcutaneously three times per week for 12 weeks in each study. Across all studies, 72 patients were treated with concomitant non cisplatin-containing chemotherapy regimens and 59 patients were treated with concomitant cisplatin-containing chemotherapy regimens. Twelve patients (19%) in the epoetin alfa arm and 10 patients (15%) in the placebo-arm dropped out prior to week 6 and are excluded from efficacy analyses.
- The safety and efficacy of Epogen were evaluated in a placebo-controlled, double-blind study (S1) enrolling 316 patients scheduled for major, elective orthopedic hip or knee surgery who were expected to require ≥ 2 units of blood and who were not able or willing to participate in an autologous blood donation program. Patients were stratified into 1 of 3 groups based on their pretreatment hemoglobin [≤ 10 g/dL (n = 2), > 10 to ≤ 13 g/dL (n = 96), and > 13 to ≤ 15 g/dL (n = 218)] and then randomly assigned to receive 300 Units/kg Epogen, 100 Units/kg Epogen, or placebo by subcutaneous injection for 10 days before surgery, on the day of surgery, and for 4 days after surgery. All patients received oral iron and a low-dose, postoperative warfarin regimen.
- Treatment with Epogen 300 Units/kg significantly (p = 0.024) reduced the risk of allogeneic RBC transfusion in patients with a pretreatment hemoglobin of > 10 to ≤ 13 g/dL; 5/31 (16%) of patients treated with Epogen 300 Units/kg, 6/26 (23%) of patients treated with Epogen 100 Units/kg, and 13/29 (45%) of placebo-treated patients were transfused. There was no significant difference in the number of patients transfused between Epogen (9% 300 Units/kg, 6% 100 Units/kg) and placebo (13%) in the > 13 to ≤ 15 g/dL hemoglobin stratum. There were too few patients in the ≤ 10 g/dL group to determine if Epogen is useful in this hemoglobin strata. In the > 10 to ≤ 13 g/dL pretreatment stratum, the mean number of units transfused per Epogen-treated patient (0.45 units blood for 300 Units/kg, 0.42 units blood for 100 Units/kg) was less than the mean transfused per placebo-treated patient (1.14 units) (overall p = 0.028). In addition, mean hemoglobin, hematocrit, and reticulocyte counts increased significantly during the presurgery period in patients treated with Epogen.
- Epogen was also evaluated in an open-label, parallel-group study (S2) enrolling 145 patients with a pretreatment hemoglobin level of ≥ 10 to ≤ 13 g/dL who were scheduled for major orthopedic hip or knee surgery and who were not participating in an autologous program. Patients were randomly assigned to receive 1 of 2 subcutaneous dosing regimens of Epogen (600 Units/kg once weekly for 3 weeks prior to surgery and on the day of surgery, or 300 Units/kg once daily for 10 days prior to surgery, on the day of surgery, and for 4 days after surgery). All patients received oral iron and appropriate pharmacologic anticoagulation therapy.
- From pretreatment to presurgery, the mean increase in hemoglobin in the 600 Units/kg weekly group (1.44 g/dL) was greater than that observed in the 300 Units/kg daily group. The mean increase in absolute reticulocyte count was smaller in the weekly group (0.11 × 106/mm3) compared to the daily group (0.17 × 106/mm3). Mean hemoglobin levels were similar for the 2 treatment groups throughout the postsurgical period.
- The erythropoietic response observed in both treatment groups resulted in similar RBC transfusion rates [11/69 (16%) in the 600 Units/kg weekly group and 14/71 (20%) in the 300 Units/kg daily group]. The mean number of units transfused per patient was approximately 0.3 units in both treatment groups.
# How Supplied
- Store at 36ºF to 46ºF (2ºC to 8ºC). Do not freeze.
- Do not shake. Protect from light; store Epogen in the carton until use.
- Do not use Epogen that has been shaken or frozen.
- Single-dose, Preservative-free Vial (in citrate-buffered formulation): 1 mL of solution contains 2000 (NDC 55513-126-10), 3000 (NDC 55513-267-10), 4000 (NDC 55513-148-10), or 10,000 Units (NDC 55513-144-10) of epoetin alfa. Each strength is supplied in dispensing packs containing 10 single-dose vials.
- Single-dose, Preservative-free Vial (in phosphate-buffered formulation): 1 mL of solution contains 40,000 Units (NDC 55513-823-10) of epoetin alfa and is supplied in dispensing packs containing 10 single-dose vials.
- Multidose, Preserved Vial: 2 mL total volume (20,000 Units total; 10,000 Units/mL). Each 1 mL of solution contains 10,000 Units (NDC 55513-283-10) of epoetin alfa, and is supplied in dispensing packs containing 10 multidose vials.
- Multidose, Preserved Vial: 1 mL total volume (20,000 Units/mL). Each 1 mL of solution contains 20,000 Units (NDC 55513-478-10) of epoetin alfa and is supplied in dispensing packs containing 10 multidose vials.
## Storage
There is limited information regarding Epoetin Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
# Precautions with Alcohol
- Alcohol-Epoetin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Epogen®[7]
# Look-Alike Drug Names
There is limited information regarding Epoetin Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Epoetin | |
b768c89ee728bc649341c659b878ef72c4778f54 | wikidoc | Eposino | Eposino
Eposino is a recombinant human erythropoietin (EPO) injection intended for intravenous (IV) or subcutaneous (SC) administration. It is produced by Shandong Kexing Bioproducts Co., Ltd., a biotechnology joint venture between Peking University Weiming Group and Sinogen (China) Ltd.
# Product Info
Erythropoietin is available as a therapeutic agent produced by recombinant DNA technology in mammalian cell cultures. It is used clinically in treating anemia resulting from chronic renal failure or from cancer chemotherapy. EPO is also one of the most widely used performance enhancing drugs in endurance sport.
Eposino is presented in vials or pre-filled single-use syringes. Unlike a traditional syringe, the Eposino rediject avoids the loss of almost 10% of the total dosage by eliminating any dead space in the chamber. Furthermore, a double-beveled thin needle reduces pain at the injection site and prevents iatrogenic infection.
# Distribution
Eposino.com, the exclusive web-based distributor of Eposino, made history when it became the first online vendor to offer rhEPO for sale globally through the internet in the mid-2000's. Eposino.com claims to offer its clients "a safe, secure, private and reliable means by which they can remotely purchase recombinant human erythropoietin (rhEPO) for quick delivery via express courier to their destination of choice."
Eposino is a registered, licensed pharmaceutical product in dozens of countries, including India - where it is distributed to pharmacies and institutions through Hindustan Bio Sciences , a limited company with a share capital of U.S $2.5 million based in Hyderabad, India.
# Controversy
The Eposino brand is not without controversy, however, as it was reported that infamous Spanish "doping" doctor Eufemiano Fuentes (Rodríguez) favored the Chinese product for the preparation of his clients, who included such stars of cycling as Ivan Basso, Jan Ullrich and Jörg Jaschke . Furthermore, Eposino.com published an unauthorized English language translation of the book L. A. Confidential : Lance Armstrong's Secrets (L. A. Confidentiel : Les secrets de Lance Armstrong) , available for download as a four-part Adobe PDF file . | Eposino
Eposino is a recombinant human erythropoietin (EPO) injection intended for intravenous (IV) or subcutaneous (SC) administration. It is produced by Shandong Kexing Bioproducts Co., Ltd., a biotechnology joint venture between Peking University Weiming Group and Sinogen (China) Ltd.
# Product Info
Erythropoietin is available as a therapeutic agent produced by recombinant DNA technology in mammalian cell cultures. It is used clinically in treating anemia resulting from chronic renal failure or from cancer chemotherapy. EPO is also one of the most widely used performance enhancing drugs in endurance sport.
Eposino is presented in vials or pre-filled single-use syringes. Unlike a traditional syringe, the Eposino rediject avoids the loss of almost 10% of the total dosage by eliminating any dead space in the chamber. Furthermore, a double-beveled thin needle reduces pain at the injection site and prevents iatrogenic infection.
# Distribution
Eposino.com, the exclusive web-based distributor of Eposino, made history when it became the first online vendor to offer rhEPO for sale globally through the internet in the mid-2000's. Eposino.com claims to offer its clients "a safe, secure, private and reliable means by which they can remotely purchase recombinant human erythropoietin (rhEPO) for quick delivery via express courier to their destination of choice."
Eposino is a registered, licensed pharmaceutical product in dozens of countries, including India - where it is distributed to pharmacies and institutions through Hindustan Bio Sciences [1], a limited company with a share capital of U.S $2.5 million based in Hyderabad, India.
# Controversy
The Eposino brand is not without controversy, however, as it was reported that infamous Spanish "doping" doctor Eufemiano Fuentes (Rodríguez) favored the Chinese product for the preparation of his clients, who included such stars of cycling as Ivan Basso, Jan Ullrich and Jörg Jaschke [2]. Furthermore, Eposino.com published an unauthorized English language translation of the book L. A. Confidential : Lance Armstrong's Secrets (L. A. Confidentiel : Les secrets de Lance Armstrong) [3], available for download as a four-part Adobe PDF file [4]. | https://www.wikidoc.org/index.php/Eposino | |
4a294b06bd4cb47457708ae0bbeb95bea2a47fa1 | wikidoc | Epoxide | Epoxide
An epoxide is a cyclic ether with only three ring atoms. This ring approximately is an equilateral triangle, i.e. its bond angles are about 60°, which makes it highly strained. The strained ring makes epoxides more reactive than other ethers, especially towards nucleophiles. Simple epoxides are named from the parent compound ethylene oxide or oxirane, such as in chloromethyloxirane. As a functional group epoxides obtain the epoxy prefix such as in the compound 1,2-epoxycycloheptane which can also be called cycloheptene epoxide.
A polymer containing unreacted epoxide units is called a polyepoxide or an epoxy. Epoxy resins are used as adhesives and structural materials. Polymerization of an epoxide gives a polyether, for example ethylene oxide polymerizes to give polyethylene glycol, also known as polyethylene oxide.
# Synthesis
Epoxides are usually created by one of the following reactions:
- Olefin Peroxidation involves the oxidation of an olefin with a peroxide, usually a peroxyacid like m-CPBA, and proceeds via what is commonly known as the Butterfly Mechanism. It is easiest to consider the oxygen to be an electrophile, and the alkene a nucleophile, although they both operate in that capacity, and the reaction is considered to be concerted (the numbers in the mechanism below are for simplification).
- Enantioselective alkene epoxidations can be found in the Sharpless epoxidation, the Jacobsen epoxidation and the Shi epoxidation.
- Intramolecular SN2 substitution. This method is a variant of the Williamson ether synthesis. In this case, the alkoxide ion and the halide are right next to each other in the same molecule (such compounds are generically called halohydrins), which makes this a simple ring closure reaction.
- In the Johnson-Corey-Chaykovsky reaction epoxides are generated from carbonyl groups and sulfonium ylides.
# Reactions
Typical epoxide reactions are listed below.
- Nucleophilic addition to an epoxide can be base or acid catalyzed.
- Under acidic conditions, the nucleophile attacks the carbon that will form the most stable carbocation, i.e. the most substituted carbon (similar to a halonium ion). Under basic conditions, the nucleophile attacks the least substituted carbon, in accordance with standard SN2 nuclephilic addition reaction process.
- Hydrolysis of an epoxide in presence of an acid catalyst generates a glycol. The hydrolysis process of epoxides can be considered to be the nucleophilic addition of water to the epoxide under acidic conditions.
- Reduction of an epoxide with lithium aluminium hydride and water generates an alcohol. This reduction process can be considered to be the nucleophilic addition of hydride (H-) to the epoxide under basic conditions.
- Reduction with tungsten hexachloride and n-butyllithium generates the alkene. This reaction in effect is a de-epoxidation : | Epoxide
An epoxide is a cyclic ether with only three ring atoms. This ring approximately is an equilateral triangle, i.e. its bond angles are about 60°, which makes it highly strained. The strained ring makes epoxides more reactive than other ethers, especially towards nucleophiles. Simple epoxides are named from the parent compound ethylene oxide or oxirane, such as in chloromethyloxirane. As a functional group epoxides obtain the epoxy prefix such as in the compound 1,2-epoxycycloheptane which can also be called cycloheptene epoxide.
A polymer containing unreacted epoxide units is called a polyepoxide or an epoxy. Epoxy resins are used as adhesives and structural materials. Polymerization of an epoxide gives a polyether, for example ethylene oxide polymerizes to give polyethylene glycol, also known as polyethylene oxide.
# Synthesis
Epoxides are usually created by one of the following reactions:
- Olefin Peroxidation involves the oxidation of an olefin with a peroxide, usually a peroxyacid like m-CPBA, and proceeds via what is commonly known as the Butterfly Mechanism.[1] It is easiest to consider the oxygen to be an electrophile, and the alkene a nucleophile, although they both operate in that capacity, and the reaction is considered to be concerted (the numbers in the mechanism below are for simplification).
- Enantioselective alkene epoxidations can be found in the Sharpless epoxidation, the Jacobsen epoxidation and the Shi epoxidation.
- Intramolecular SN2 substitution. This method is a variant of the Williamson ether synthesis. In this case, the alkoxide ion and the halide are right next to each other in the same molecule (such compounds are generically called halohydrins), which makes this a simple ring closure reaction.
- In the Johnson-Corey-Chaykovsky reaction epoxides are generated from carbonyl groups and sulfonium ylides.
# Reactions
Typical epoxide reactions are listed below.
- Nucleophilic addition to an epoxide can be base or acid catalyzed.
- Under acidic conditions, the nucleophile attacks the carbon that will form the most stable carbocation, i.e. the most substituted carbon (similar to a halonium ion). Under basic conditions, the nucleophile attacks the least substituted carbon, in accordance with standard SN2 nuclephilic addition reaction process.
- Hydrolysis of an epoxide in presence of an acid catalyst generates a glycol. The hydrolysis process of epoxides can be considered to be the nucleophilic addition of water to the epoxide under acidic conditions.
- Reduction of an epoxide with lithium aluminium hydride and water generates an alcohol. This reduction process can be considered to be the nucleophilic addition of hydride (H-) to the epoxide under basic conditions.
- Reduction with tungsten hexachloride and n-butyllithium generates the alkene. This reaction in effect is a de-epoxidation [2]: | https://www.wikidoc.org/index.php/Epoxidation | |
24e550c7f6fb936dd6f284059a92367a276080ca | wikidoc | Lithium | Lithium
# Overview
Lithium is a chemical element with symbol Li and atomic number 3. It is a soft, silver-white metal belonging to the alkali metal group of chemical elements. Under standard conditions it is the lightest metal and the least dense solid element. Like all alkali metals, lithium is highly reactive and flammable. For this reason, it is typically stored in mineral oil. When cut open, lithium exhibits a metallic luster, but contact with moist air corrodes the surface quickly to a dull silvery gray, then black tarnish. Because of its high reactivity, lithium never occurs freely in nature, and instead, only appears in compounds, which are usually ionic. Lithium occurs in a number of pegmatitic minerals, but due to its solubility as an ion is present in ocean water and is commonly obtained from brines and clays. On a commercial scale, lithium is isolated electrolytically from a mixture of lithium chloride and potassium chloride.
The nuclei of lithium verge on instability, since the two stable lithium isotopes found in nature have among the lowest binding energies per nucleon of all stable nuclides. Because of its relative nuclear instability, lithium is less common in the solar system than 25 of the first 32 chemical elements even though the nuclei are very light in atomic weight. For related reasons, lithium has important links to nuclear physics. The transmutation of lithium atoms to helium in 1932 was the first fully man-made nuclear reaction, and lithium-6 deuteride serves as a fusion fuel in staged thermonuclear weapons.
Lithium and its compounds have several industrial applications, including heat-resistant glass and ceramics, high strength-to-weight alloys used in aircraft, lithium batteries and lithium-ion batteries. These uses consume more than half of lithium production.
Trace amounts of lithium are present in all organisms. The element serves no apparent vital biological function, since animals and plants survive in good health without it. Non-vital functions have not been ruled out. The lithium ion Li+ administered as any of several lithium salts has proved to be useful as a mood-stabilizing drug in the treatment of bipolar disorder, due to neurological effects of the ion in the human body.
## Atomic and Physical
Like the other alkali metals, lithium has a single valence electron that is easily given up to form a cation. Because of this, it is a good conductor of heat and electricity as well as a highly reactive element, though the least reactive of the alkali metals. Lithium's low reactivity compared to other alkali metals is due to the proximity of its valence electron to its nucleus (the remaining two electrons are in lithium's 1s orbital and are much lower in energy, and therefore they do not participate in chemical bonds).
Lithium metal is soft enough to be cut with a knife. When cut, it possesses a silvery-white color that quickly changes to gray due to oxidation. While it has one of the lowest melting points among all metals (180 °C), it has the highest melting and boiling points of the alkali metals.
Lithium has a very low density of 0.534 g/cm3, comparable with that of pine wood. It is the least dense of all elements that are solids at room temperature, the next lightest solid element (potassium, at 0.862 g/cm3) being more than 60% denser. Furthermore, apart from helium and hydrogen, it is less dense than any liquid element, being only 2/3 as dense as liquid nitrogen (0.808 g/cm3). Lithium can float on the lightest hydrocarbon oils and is one of only three metals that can float on water, the other two being sodium and potassium.
Lithium's coefficient of thermal expansion is twice that of aluminium and almost four times that of iron. It has the highest specific heat capacity of any solid element. Lithium is superconductive below 400 μK at standard pressure and at higher temperatures (more than 9 K) at very high pressures (>20 GPa) At temperatures below 70 K, lithium, like sodium, undergoes diffusionless phase change transformations. At 4.2 K it has a rhombohedral crystal system (with a nine-layer repeat spacing); at higher temperatures it transforms to face-centered cubic and then body-centered cubic. At liquid-helium temperatures (4 K) the rhombohedral structure is the most prevalent. Multiple allotropic forms have been reported for lithium at high pressures.
Lithium has a specific heat capacity of 3.58 kilojoules per kilogram-Kelvin, the highest of all solids. Because of this, lithium metal is often used in coolants for heat transfer applications.
## Chemistry and compounds
Lithium reacts with water easily, but with noticeably less energy than other alkali metals do. The reaction forms hydrogen gas and lithium hydroxide in aqueous solution. Because of its reactivity with water, lithium is usually stored under cover of a hydrocarbon, often petroleum jelly. Though the heavier alkali metals can be stored in more dense substances, such as mineral oil, lithium is not dense enough to be fully submerged in these liquids. In moist air, lithium rapidly tarnishes to form a black coating of lithium hydroxide (LiOH and LiOH·H2O), lithium nitride (Li3N) and lithium carbonate (Li2CO3, the result of a secondary reaction between LiOH and CO2).
When placed over a flame, lithium compounds give off a striking crimson color, but when it burns strongly the flame becomes a brilliant silver. Lithium will ignite and burn in oxygen when exposed to water or water vapors. Lithium is flammable, and it is potentially explosive when exposed to air and especially to water, though less so than the other alkali metals. The lithium-water reaction at normal temperatures is brisk but nonviolent, as the hydrogen produced will not ignite on its own. As with all alkali metals, lithium fires are difficult to extinguish, requiring dry powder fire extinguishers, specifically the Class D type (see Types of extinguishing agents). Lithium is the only metal which reacts with nitrogen under normal conditions.
Lithium has a diagonal relationship with magnesium, an element of similar atomic and ionic radius. Chemical resemblances between the two metals include the formation of a nitride by reaction with N2, the formation of an oxide (Li2O) and peroxide (Li2O2) when burnt in O2, salts with similar solubilities, and thermal instability of the carbonates and nitrides. The metal reacts with hydrogen gas at high temperatures to produce lithium hydride (LiH).
Other known binary compounds include the halides (LiF, LiCl, LiBr, LiI), and the sulfide (Li2S), the superoxide (LiO2), carbide (Li2C2). Many other inorganic compounds are known, where lithium combines with anions to form various salts: borates, amides, carbonate, nitrate, or borohydride (LiBH4). Multiple organolithium reagents are known where there is a direct bond between carbon and lithium atoms effectively creating a carbanion. These are extremely powerful bases and nucleophiles. In many of these organolithium compounds, the lithium ions tend to aggregate into high-symmetry clusters by themselves, which is relatively common for alkali cations. LiHe, a very weakly interacting van der Waals compound, has been detected at very low temperatures.
## Isotopes
Naturally occurring lithium is composed of two stable isotopes, 6Li and 7Li, the latter being the more abundant (92.5% natural abundance). Both natural isotopes have anomalously low nuclear binding energy per nucleon compared to the next lighter and heavier elements, helium and beryllium, which means that alone among stable light elements, lithium can produce net energy through nuclear fission. The two lithium nuclei have lower binding energies per nucleon than any other stable nuclides other than deuterium and helium-3. As a result of this, though very light in atomic weight, lithium is less common in the solar system than 25 of the first 32 chemical elements.
Seven radioisotopes have been characterized, the most stable being 8Li with a half-life of 838 ms and 9Li with a half-life of 178 ms. All of the remaining radioactive isotopes have half-lives that are shorter than 8.6 ms. The shortest-lived isotope of lithium is 4Li, which decays through proton emission and has a half-life of 7.6 × 10−23 s.
7Li is one of the primordial elements (or, more properly, primordial nuclides) produced in Big Bang nucleosynthesis. A small amount of both 6Li and 7Li are produced in stars, but are thought to be burned as fast as produced. Additional small amounts of lithium of both 6Li and 7Li may be generated from solar wind, cosmic rays hitting heavier atoms, and from early solar system 7Be and 10Be radioactive decay. While lithium is created in stars during the Stellar nucleosynthesis, it is further burnt. 7Li can also be generated in carbon stars.
Lithium isotopes fractionate substantially during a wide variety of natural processes, including mineral formation (chemical precipitation), metabolism, and ion exchange. Lithium ions substitute for magnesium and iron in octahedral sites in clay minerals, where 6Li is preferred to 7Li, resulting in enrichment of the light isotope in processes of hyperfiltration and rock alteration. The exotic 11Li is known to exhibit a nuclear halo. The process known as laser isotope separation can be used to separate lithium isotopes.
Nuclear weapons manufacture and other nuclear physics uses are a major source of artificial lithium fractionation, with the light isotope 6Li being retained by industry and military stockpiles to such an extent as to slightly but measurably change the 6Li to 7Li ratios even in natural sources, such as rivers. This has led to unusual uncertainty in the standardized atomic weight of lithium, since this quantity depends on the natural abundance ratios of these naturally-occurring stable lithium isotopes, as they are available in commercial lithium mineral sources.
## Astronomical
According to modern cosmological theory, lithium—as both of its stable isotopes lithium-6 and lithium-7—was among the 3 elements synthesized in the Big Bang. Though the amount of lithium generated in Big Bang nucleosynthesis is dependent upon the number of photons per baryon, for accepted values the lithium abundance can be calculated, and there is a "cosmological lithium discrepancy" in the Universe: older stars seem to have less lithium than they should, and some younger stars have far more. The lack of lithium in older stars is apparently caused by the "mixing" of lithium into the interior of stars, where it is destroyed. Furthermore, lithium is produced in younger stars. Though it transmutes into two atoms of helium due to collision with a proton at temperatures above 2.4 million degrees Celsius (most stars easily attain this temperature in their interiors), lithium is more abundant than predicted in later-generation stars, for causes not yet completely understood.
Though it was one of the three first elements (together with helium and hydrogen) to be synthesized in the Big Bang, lithium, together with beryllium and boron are markedly less abundant than other nearby elements. This is a result of the low temperature necessary to destroy lithium, and a lack of common processes to produce it.
Lithium is also found in brown dwarf substellar objects and certain anomalous orange stars. Because lithium is present in cooler, less-massive brown dwarfs, but is destroyed in hotter red dwarf stars, its presence in the stars' spectra can be used in the "lithium test" to differentiate the two, as both are smaller than the Sun. Certain orange stars can also contain a high concentration of lithium. Those orange stars found to have a higher than usual concentration of lithium (such as Centaurus X-4) orbit massive objects—neutron stars or black holes—whose gravity evidently pulls heavier lithium to the surface of a hydrogen-helium star, causing more lithium to be observed.
## Terrestrial
Although lithium is widely distributed on Earth, it does not naturally occur in elemental form due to its high reactivity. The total lithium content of seawater is very large and is estimated as 230 billion tonnes, where the element exists at a relatively constant concentration of 0.14 to 0.25 parts per million (ppm), or 25 micromolar;
higher concentrations approaching 7 ppm are found near hydrothermal vents.
Estimates for crustal content range from 20 to 70 ppm by weight. In keeping with its name, lithium forms a minor part of igneous rocks, with the largest concentrations in granites. Granitic pegmatites also provide the greatest abundance of lithium-containing minerals, with spodumene and petalite being the most commercially viable sources. Another significant mineral of lithium is lepidolite. A newer source for lithium is hectorite clay, the only active development of which is through the Western Lithium Corporation in the United States. At 20 mg lithium per kg of Earth's crust, lithium is the 25th most abundant element.
According to the Handbook of Lithium and Natural Calcium, "Lithium is a comparatively rare element, although it is found in many rocks and some brines, but always in very low concentrations. There are a fairly large number of both lithium mineral and brine deposits but only comparatively few of them are of actual or potential commercial value. Many are very small, others are too low in grade."
One of the largest reserve base of lithium is in the Salar de Uyuni area of Bolivia, which has 5.4 million tonnes. US Geological Survey, estimates that in 2010 Chile had the largest reserves by far (7.5 million tonnes) and the highest annual production (8,800 tonnes). Other major suppliers include Australia, Argentina and China.
In June 2010, the New York Times reported that American geologists were conducting ground surveys on dry salt lakes in western Afghanistan believing that large deposits of lithium are located there. "Pentagon officials said that their initial analysis at one location in Ghazni Province showed the potential for lithium deposits as large as those of Bolivia, which now has the world's largest known lithium reserves." These estimates are "based principally on old data, which was gathered mainly by the Soviets during their occupation of Afghanistan from 1979–1989" and "Stephen Peters, the head of the USGS's Afghanistan Minerals Project, said that he was unaware of USGS involvement in any new surveying for minerals in Afghanistan in the past two years. 'We are not aware of any discoveries of lithium,' he said."
## Biological
Lithium is found in trace amount in numerous plants, plankton, and invertebrates, at concentrations of 69 to 5,760 parts per billion (ppb). In vertebrates the concentration is slightly lower, and nearly all vertebrate tissue and body fluids have been found to contain lithium ranging from 21 to 763 ppb. Marine organisms tend to bioaccumulate lithium more than terrestrial ones. It is not known whether lithium has a physiological role in any of these organisms, but nutritional studies in mammals have indicated its importance to health, leading to a suggestion that it be classed as an essential trace element with an RDA of 1 mg/day. Observational studies in Japan, reported in 2011, suggested that naturally occurring lithium in drinking water may increase human lifespan.
# History of discovery and use
Petalite (LiAlSi4O10) was discovered in 1800 by the Brazilian chemist and statesman José Bonifácio de Andrada e Silva in a mine on the island of Utö, Sweden. However, it was not until 1817 that Johan August Arfwedson, then working in the laboratory of the chemist Jöns Jakob Berzelius, detected the presence of a new element while analyzing petalite ore. This element formed compounds similar to those of sodium and potassium, though its carbonate and hydroxide were less soluble in water and more alkaline. Berzelius gave the alkaline material the name "lithion/lithina", from the Greek word λιθoς (transliterated as lithos, meaning "stone"), to reflect its discovery in a solid mineral, as opposed to potassium, which had been discovered in plant ashes, and sodium which was known partly for its high abundance in animal blood. He named the metal inside the material "lithium".
Arfwedson later showed that this same element was present in the minerals spodumene and lepidolite. In 1818, Christian Gmelin was the first to observe that lithium salts give a bright red color to flame. However, both Arfwedson and Gmelin tried and failed to isolate the pure element from its salts. It was not isolated until 1821, when William Thomas Brande obtained it by electrolysis of lithium oxide, a process that had previously been employed by the chemist Sir Humphry Davy to isolate the alkali metals potassium and sodium. Brande also described some pure salts of lithium, such as the chloride, and, estimating that lithia (lithium oxide) contained about 55% metal, estimated the atomic weight of lithium to be around 9.8 g/mol (modern value ~6.94 g/mol). In 1855, larger quantities of lithium were produced through the electrolysis of lithium chloride by Robert Bunsen and Augustus Matthiessen. The discovery of this procedure henceforth led to commercial production of lithium, beginning in 1923, by the German company Metallgesellschaft AG, which performed an electrolysis of a liquid mixture of lithium chloride and potassium chloride.
The production and use of lithium underwent several drastic changes in history. The first major application of lithium was in high-temperature lithium greases for aircraft engines or similar applications in World War II and shortly after. This use was supported by the fact that lithium-based soaps have a higher melting point than other alkali soaps, and are less corrosive than calcium based soaps. The small market for lithium soaps and the lubricating greases based upon them was supported by several small mining operations mostly in the United States.
The demand for lithium increased dramatically during the Cold War with the production of nuclear fusion weapons. Both lithium-6 and lithium-7 produce tritium when irradiated by neutrons, and are thus useful for the production of tritium by itself, as well as a form of solid fusion fuel used inside hydrogen bombs in the form of lithium deuteride. The United States became the prime producer of lithium in the period between the late 1950s and the mid-1980s. At the end, the stockpile of lithium was roughly 42,000 tonnes of lithium hydroxide. The stockpiled lithium was depleted in lithium-6 by 75%, which was enough to affect the measured atomic weight of lithium in many standardized chemicals, and even the atomic weight of lithium in some "natural sources" of lithium ion which had been "contaminated" by lithium salts discharged from isotope separation facilities, which had found its way into ground water.
Lithium was used to decrease the melting temperature of glass and to improve the melting behavior of aluminium oxide when using the Hall-Héroult process. These two uses dominated the market until the middle of the 1990s. After the end of the nuclear arms race the demand for lithium decreased and the sale of Department of Energy stockpiles on the open market further reduced prices. But in the mid-1990s, several companies started to extract lithium from brine which proved to be a less expensive method than underground or even open-pit mining. Most of the mines closed or shifted their focus to other materials as only the ore from zoned pegmatites could be mined for a competitive price. For example, the US mines near Kings Mountain, North Carolina closed before the turn of the 21st century.
The use in lithium ion batteries increased the demand for lithium and became the dominant use in 2007. With the surge of lithium demand in batteries in the 2000s, new companies have expanded brine extraction efforts to meet the rising demand.
Lithium toxicity must be differentiated from other causes of hypercalcaemia
Lithium toxicity must be differentiated from other causes of diabetes insipidus.
# Production
Since the end of World War II lithium production has greatly increased. The metal is separated from other elements in igneous minerals such as those above. Lithium salts are extracted from the water of mineral springs, brine pools and brine deposits. The metal is produced electrolytically from a mixture of fused 55% lithium chloride and 45% potassium chloride at about 450o C. In 1998 it was about 95 US$ / kg (or 43 US$/pound).
Worldwide identified reserves of lithium in 2008 were estimated by the US Geological Survey as 13 million tonnes. Deposits of lithium are found in South America throughout the Andes mountain chain. Chile is the leading lithium producer, followed by Argentina. Both countries recover the lithium from brine pools. In the United States lithium is recovered from brine pools in Nevada. However, half the world's known reserves are located in Bolivia, a nation sitting along the central eastern slope of the Andes.
In 2009 Bolivia was negotiating with Japanese, French, and Korean firms to begin extraction. According to the US Geological Survey, Bolivia's Uyuni Desert has 5.4 million tonnes of lithium. A newly discovered deposit in Wyoming's Rock Springs Uplift is estimated at 228,000 tons. Additional deposits in the same formation were extrapolated to be as much as 18 million tons.
After an industry wide pricing reduction for lithium carbonate after the Great Financial Crisis, where major suppliers such as Sociedad Química y Minera (SQM) dropped pricing by 20% in light of incoming lithium resource developers and to further defend their market position, pricing in 2012 scaled up due to increased lithium demand. A 2012 Business Week article outlined the existing oligopoly in the lithium space, "SQM, controlled by billionaire Julio Ponce, is the second-largest, followed by Rockwood, which is backed by Henry Kravis’s KKR & Co., and Philadelphia-based FMC." Global consumption may jump to 300,000 metric tons a year by 2020 from about 150,000 tons in 2012, as demand for lithium batteries has been growing at about 25 percent a year, outpacing the 4 percent to 5 percent overall gain in lithium
A potential source is geothermal wells. Geothermal fluids carry leachates to the surface; recovery of lithium has been demonstrated in the field. As the lithium is separated by simple filtration techniques, the process and environmental costs are primarily that of the already-operating geothermal well; relative environmental impacts may thus be positive.
There are differing opinions about the potential growth of lithium production. According to a 2011 study conducted at Lawrence Berkeley National Laboratory and the University of California Berkeley, the currently estimated reserve base of lithium should not be a limiting factor for large-scale battery production for electric vehicles, as the study estimated that on the order of 1 billion 40 kWh Li-based batteries could be built with current reserves. Another 2011 study by researchers from the University of Michigan and Ford Motor Company found that there are sufficient lithium resources to support global demand until 2100, including the lithium required for the potential widespread use of hybrid electric, plug-in hybrid electric and battery electric vehicles. The study estimated global lithium reserves at 39 million tons, and total demand for lithium during the 90-year period analyzed at 12–20 million tons, depending on the scenarios regarding economic growth and recycling rates.
However, another study concluded that "realistically achievable lithium carbonate production will be sufficient for only a small fraction of future PHEV and EV global market requirements", that "demand from the portable electronics sector will absorb much of the planned production increases in the next decade", and that "mass production of lithium carbonate is not environmentally sound, it will cause irreparable ecological damage to ecosystems that should be protected and that LiIon propulsion is incompatible with the notion of the 'Green Car'.
## Ceramics and glass
Lithium oxide is a widely used flux for processing silica, reducing the melting point and viscosity of the material and leading to glazes of improved physical properties including low coefficients for thermal expansion. Lithium oxides are a component of ovenware. Worldwide, this is the single largest use for lithium compounds. Lithium carbonate (Li2CO3) is generally used in this application: upon heating it converts to the oxide.
## Electrical and electronics
In the later years of the 20th century, owing to its high electrochemical potential, lithium became an important component of the electrolyte and of one of the electrodes in batteries. A typical lithium-ion battery can generate approximately 3 volts, compared with 2.1 volts for lead-acid or 1.5 volts for zinc-carbon cells. Because of its low atomic mass, it also has a high charge- and power-to-weight ratio. Lithium batteries are disposable (primary) batteries with lithium or its compounds as an anode. Lithium batteries are not to be confused with lithium-ion batteries, which are high energy-density rechargeable batteries. Other rechargeable batteries include the lithium-ion polymer battery, lithium iron phosphate battery, and the nanowire battery.
## Lubricating greases
The third most common use of lithium is in greases. Lithium hydroxide is a strong base and, when heated with a fat, produces a soap made of lithium stearate. Lithium soap has the ability to thicken oils, and it is used to manufacture all-purpose, high-temperature lubricating greases.
## Metallurgy
When used as a flux for welding or soldering, metallic lithium promotes the fusing of metals during the process and eliminates the forming of oxides by absorbing impurities. Its fusing quality is also important as a flux for producing ceramics, enamels and glass. Alloys of the metal with aluminium, cadmium, copper and manganese are used to make high-performance aircraft parts (see also Lithium-aluminium alloys).
### Pyrotechnics
Lithium compounds are used as pyrotechnic colorants and oxidizers in red fireworks and flares.
### Air purification
Lithium chloride and lithium bromide are hygroscopic and are used as desiccants for gas streams. Lithium hydroxide and lithium peroxide are the salts most used in confined areas, such as aboard spacecraft and submarines, for carbon dioxide removal and air purification. Lithium hydroxide absorbs carbon dioxide from the air by forming lithium carbonate, and is preferred over other alkaline hydroxides for its low weight.
Lithium peroxide (Li2O2) in presence of moisture not only reacts with carbon dioxide to form lithium carbonate, but also releases oxygen. The reaction is as follows:
Some of the aforementioned compounds, as well as lithium perchlorate, are used in oxygen candles that supply submarines with oxygen. These can also include small amounts of boron, magnesium, aluminum, silicon, titanium, manganese, and iron.
### Optics
Lithium fluoride, artificially grown as crystal, is clear and transparent and often used in specialist optics for IR, UV and VUV (vacuum UV) applications. It has one of the lowest refractive indexes and the farthest transmission range in the deep UV of most common materials. Finely divided lithium fluoride powder has been used for thermoluminescent radiation dosimetry (TLD): when a sample of such is exposed to radiation, it accumulates crystal defects which, when heated, resolve via a release of bluish light whose intensity is proportional to the absorbed dose, thus allowing this to be quantified. Lithium fluoride is sometimes used in focal lenses of telescopes.
The high non-linearity of lithium niobate also makes it useful in non-linear optics applications. It is used extensively in telecommunication products such as mobile phones and optical modulators, for such components as resonant crystals. Lithium applications are used in more than 60% of mobile phones.
### Organic and polymer chemistry
Organolithium compounds are widely used in the production of polymer and fine-chemicals. In the polymer industry, which is the dominant consumer of these reagents, alkyl lithium compounds are catalysts/initiators. in anionic polymerization of unfunctionalized olefins. For the production of fine chemicals, organolithium compounds function as strong bases and as reagents for the formation of carbon-carbon bonds. Organolithium compounds are prepared from lithium metal and alkyl halides.
Many other lithium compounds are used as reagents to prepare organic compounds. Some popular compounds include lithium aluminium hydride (LiAlH4), lithium triethylborohydride (LiBH(C2H5)3).
### Military applications
Metallic lithium and its complex hydrides, such as Li, are used as high energy additives to rocket propellants. Lithium aluminum hydride can also be used by itself as a solid fuel.
The Mark 50 Torpedo stored chemical energy propulsion system (SCEPS) uses a small tank of sulfur hexafluoride gas which is sprayed over a block of solid lithium. The reaction generates heat which is used to generate steam. The steam propels the torpedo in a closed Rankine cycle.
Lithium hydride containing lithium-6 is used in hydrogen bombs. In the bomb, it is placed around the core of an atomic bomb.
## Nuclear
Lithium-6 is valued as a source material for tritium production and as a neutron absorber in nuclear fusion. Natural lithium contains about 7.5% lithium-6 from which large amounts of lithium-6 have been produced by isotope separation for use in nuclear weapons. Lithium-7 gained interest for use in nuclear reactor coolants.
Lithium deuteride was the fusion fuel of choice in early versions of the hydrogen bomb. When bombarded by neutrons, both 6Li and 7Li produce tritium — this reaction, which was not fully understood when hydrogen bombs were first tested, was responsible for the runaway yield of the Castle Bravo nuclear test. Tritium fuses with deuterium in a fusion reaction that is relatively easy to achieve. Although details remain secret, lithium-6 deuteride still apparently plays a role in modern nuclear weapons, as a fusion material.
Lithium fluoride, when highly enriched in the lithium-7 isotope, forms the basic constituent of the fluoride salt mixture LiF-BeF2 used in liquid fluoride nuclear reactors. Lithium fluoride is exceptionally chemically stable and LiF-BeF2 mixtures have low melting points. In addition, 7Li, Be, and F are among the few nuclides with low enough thermal neutron capture cross-sections not to poison the fission reactions inside a nuclear fission reactor.
In conceptualized nuclear fusion power plants, lithium will be used to produce tritium in magnetically confined reactors using deuterium and tritium as the fuel. Naturally occurring tritium is extremely rare, and must be synthetically produced by surrounding the reacting plasma with a 'blanket' containing lithium where neutrons from the deuterium-tritium reaction in the plasma will fission the lithium to produce more tritium:
Lithium is also used as a source for alpha particles, or helium nuclei. When 7Li is bombarded by accelerated protons 8Be is formed, which undergoes fission to form two alpha particles. This feat, called "splitting the atom" at the time, was the first fully man-made nuclear reaction. It was produced by Cockroft and Walton in 1932. (Nuclear reactions and human-directed nuclear transmutation had been accomplished as early as 1917, but by using natural radioactive bombardment with alpha particles).
## Medicine
In the treatment of bipolar disorder, lithium compounds are used. Lithium salts may also be helpful for related diagnoses, such as schizoaffective disorder and cyclic major depression. The active principle in these salts is the lithium ion Li+. There have been suggestions of increased risk of developing Ebstein's cardiac anomaly in infants born to women taking lithium during the first trimester of pregnancy.
# Precautions
Lithium is corrosive and requires special handling to avoid skin contact. Breathing lithium dust or lithium compounds (which are often alkaline) initially irritate the nose and throat, while higher exposure can cause a buildup of fluid in the lungs, leading to pulmonary edema. The metal itself is a handling hazard because of the caustic hydroxide produced when it is in contact with moisture. Lithium is safely stored in non-reactive compounds such as naphtha.
## Regulation
Some jurisdictions limit the sale of lithium batteries, which are the most readily available source of lithium for ordinary consumers. Lithium can be used to reduce pseudoephedrine and ephedrine to methamphetamine in the Birch reduction method, which employs solutions of alkali metals dissolved in anhydrous ammonia.
Carriage and shipment of some kinds of lithium batteries may be prohibited aboard certain types of transportation (particularly aircraft) because of the ability of most types of lithium batteries to fully discharge very rapidly when short-circuited, leading to overheating and possible explosion in a process called thermal runaway. Most consumer lithium batteries have thermal overload protection built-in to prevent this type of incident, or their design inherently limits short-circuit currents. Internal shorts have been known to develop due to manufacturing defects or damage to batteries that can lead to spontaneous thermal runaway.
# Notes
- ↑ Densities for all the gaseous elements can be obtained at Airliquide.com
- ↑ Apendixes. By USGS definitions, reserve base "may encompass those parts of the resources that have a reasonable potential for becoming economically available within planning horizons beyond those that assume proven technology and current economics. The reserve base includes those resources that are currently economic (reserves), marginally economic (marginal reserves), and some of those that are currently subeconomic (subeconomic resources)."
- ↑ Beryllium and fluorine occur only as one isotope, 9Be and 19F respectively. These two, together with 7Li, as well as 2H, 11B, 15N, 209Bi, and the stable isotopes of C, and O, are the only nuclides with low enough thermal neutron capture cross sections aside from actinides to serve as major constituents of a molten salt breeder reactor fuel. | Lithium
Template:Seealso
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]
# Overview
Lithium is a chemical element with symbol Li and atomic number 3. It is a soft, silver-white metal belonging to the alkali metal group of chemical elements. Under standard conditions it is the lightest metal and the least dense solid element. Like all alkali metals, lithium is highly reactive and flammable. For this reason, it is typically stored in mineral oil. When cut open, lithium exhibits a metallic luster, but contact with moist air corrodes the surface quickly to a dull silvery gray, then black tarnish. Because of its high reactivity, lithium never occurs freely in nature, and instead, only appears in compounds, which are usually ionic. Lithium occurs in a number of pegmatitic minerals, but due to its solubility as an ion is present in ocean water and is commonly obtained from brines and clays. On a commercial scale, lithium is isolated electrolytically from a mixture of lithium chloride and potassium chloride.
The nuclei of lithium verge on instability, since the two stable lithium isotopes found in nature have among the lowest binding energies per nucleon of all stable nuclides. Because of its relative nuclear instability, lithium is less common in the solar system than 25 of the first 32 chemical elements even though the nuclei are very light in atomic weight.[1] For related reasons, lithium has important links to nuclear physics. The transmutation of lithium atoms to helium in 1932 was the first fully man-made nuclear reaction, and lithium-6 deuteride serves as a fusion fuel in staged thermonuclear weapons.[2]
Lithium and its compounds have several industrial applications, including heat-resistant glass and ceramics, high strength-to-weight alloys used in aircraft, lithium batteries and lithium-ion batteries. These uses consume more than half of lithium production.
Trace amounts of lithium are present in all organisms. The element serves no apparent vital biological function, since animals and plants survive in good health without it. Non-vital functions have not been ruled out. The lithium ion Li+ administered as any of several lithium salts has proved to be useful as a mood-stabilizing drug in the treatment of bipolar disorder, due to neurological effects of the ion in the human body.
## Atomic and Physical
Like the other alkali metals, lithium has a single valence electron that is easily given up to form a cation.[3] Because of this, it is a good conductor of heat and electricity as well as a highly reactive element, though the least reactive of the alkali metals. Lithium's low reactivity compared to other alkali metals is due to the proximity of its valence electron to its nucleus (the remaining two electrons are in lithium's 1s orbital and are much lower in energy, and therefore they do not participate in chemical bonds).[3]
Lithium metal is soft enough to be cut with a knife. When cut, it possesses a silvery-white color that quickly changes to gray due to oxidation.[3] While it has one of the lowest melting points among all metals (180 °C), it has the highest melting and boiling points of the alkali metals.[4]
Lithium has a very low density of 0.534 g/cm3, comparable with that of pine wood. It is the least dense of all elements that are solids at room temperature, the next lightest solid element (potassium, at 0.862 g/cm3) being more than 60% denser. Furthermore, apart from helium and hydrogen, it is less dense than any liquid element, being only 2/3 as dense as liquid nitrogen (0.808 g/cm3).[note 1][5] Lithium can float on the lightest hydrocarbon oils and is one of only three metals that can float on water, the other two being sodium and potassium.
Lithium's coefficient of thermal expansion is twice that of aluminium and almost four times that of iron.[6] It has the highest specific heat capacity of any solid element. Lithium is superconductive below 400 μK at standard pressure[7] and at higher temperatures (more than 9 K) at very high pressures (>20 GPa)[8] At temperatures below 70 K, lithium, like sodium, undergoes diffusionless phase change transformations. At 4.2 K it has a rhombohedral crystal system (with a nine-layer repeat spacing); at higher temperatures it transforms to face-centered cubic and then body-centered cubic. At liquid-helium temperatures (4 K) the rhombohedral structure is the most prevalent.[9] Multiple allotropic forms have been reported for lithium at high pressures.[10]
Lithium has a specific heat capacity of 3.58 kilojoules per kilogram-Kelvin, the highest of all solids.[11][12] Because of this, lithium metal is often used in coolants for heat transfer applications.[11]
## Chemistry and compounds
Lithium reacts with water easily, but with noticeably less energy than other alkali metals do. The reaction forms hydrogen gas and lithium hydroxide in aqueous solution.[3] Because of its reactivity with water, lithium is usually stored under cover of a hydrocarbon, often petroleum jelly. Though the heavier alkali metals can be stored in more dense substances, such as mineral oil, lithium is not dense enough to be fully submerged in these liquids.[13] In moist air, lithium rapidly tarnishes to form a black coating of lithium hydroxide (LiOH and LiOH·H2O), lithium nitride (Li3N) and lithium carbonate (Li2CO3, the result of a secondary reaction between LiOH and CO2).[14]
When placed over a flame, lithium compounds give off a striking crimson color, but when it burns strongly the flame becomes a brilliant silver. Lithium will ignite and burn in oxygen when exposed to water or water vapors.[15] Lithium is flammable, and it is potentially explosive when exposed to air and especially to water, though less so than the other alkali metals. The lithium-water reaction at normal temperatures is brisk but nonviolent, as the hydrogen produced will not ignite on its own. As with all alkali metals, lithium fires are difficult to extinguish, requiring dry powder fire extinguishers, specifically the Class D type (see Types of extinguishing agents). Lithium is the only metal which reacts with nitrogen under normal conditions.[16][17]
Lithium has a diagonal relationship with magnesium, an element of similar atomic and ionic radius. Chemical resemblances between the two metals include the formation of a nitride by reaction with N2, the formation of an oxide (Li2O) and peroxide (Li2O2) when burnt in O2, salts with similar solubilities, and thermal instability of the carbonates and nitrides.[14][18] The metal reacts with hydrogen gas at high temperatures to produce lithium hydride (LiH).[19]
Other known binary compounds include the halides (LiF, LiCl, LiBr, LiI), and the sulfide (Li2S), the superoxide (LiO2), carbide (Li2C2). Many other inorganic compounds are known, where lithium combines with anions to form various salts: borates, amides, carbonate, nitrate, or borohydride (LiBH4). Multiple organolithium reagents are known where there is a direct bond between carbon and lithium atoms effectively creating a carbanion. These are extremely powerful bases and nucleophiles. In many of these organolithium compounds, the lithium ions tend to aggregate into high-symmetry clusters by themselves, which is relatively common for alkali cations.[20] LiHe, a very weakly interacting van der Waals compound, has been detected at very low temperatures.[21]
## Isotopes
Naturally occurring lithium is composed of two stable isotopes, 6Li and 7Li, the latter being the more abundant (92.5% natural abundance).[3][13][22] Both natural isotopes have anomalously low nuclear binding energy per nucleon compared to the next lighter and heavier elements, helium and beryllium, which means that alone among stable light elements, lithium can produce net energy through nuclear fission. The two lithium nuclei have lower binding energies per nucleon than any other stable nuclides other than deuterium and helium-3. As a result of this, though very light in atomic weight, lithium is less common in the solar system than 25 of the first 32 chemical elements.[1]
Seven radioisotopes have been characterized, the most stable being 8Li with a half-life of 838 ms and 9Li with a half-life of 178 ms. All of the remaining radioactive isotopes have half-lives that are shorter than 8.6 ms. The shortest-lived isotope of lithium is 4Li, which decays through proton emission and has a half-life of 7.6 × 10−23 s.[23]
7Li is one of the primordial elements (or, more properly, primordial nuclides) produced in Big Bang nucleosynthesis. A small amount of both 6Li and 7Li are produced in stars, but are thought to be burned as fast as produced.[24] Additional small amounts of lithium of both 6Li and 7Li may be generated from solar wind, cosmic rays hitting heavier atoms, and from early solar system 7Be and 10Be radioactive decay.[25] While lithium is created in stars during the Stellar nucleosynthesis, it is further burnt. 7Li can also be generated in carbon stars.[26]
Lithium isotopes fractionate substantially during a wide variety of natural processes,[27] including mineral formation (chemical precipitation), metabolism, and ion exchange. Lithium ions substitute for magnesium and iron in octahedral sites in clay minerals, where 6Li is preferred to 7Li, resulting in enrichment of the light isotope in processes of hyperfiltration and rock alteration. The exotic 11Li is known to exhibit a nuclear halo. The process known as laser isotope separation can be used to separate lithium isotopes.[28]
Nuclear weapons manufacture and other nuclear physics uses are a major source of artificial lithium fractionation, with the light isotope 6Li being retained by industry and military stockpiles to such an extent as to slightly but measurably change the 6Li to 7Li ratios even in natural sources, such as rivers. This has led to unusual uncertainty in the standardized atomic weight of lithium, since this quantity depends on the natural abundance ratios of these naturally-occurring stable lithium isotopes, as they are available in commercial lithium mineral sources.[29]
## Astronomical
According to modern cosmological theory, lithium—as both of its stable isotopes lithium-6 and lithium-7—was among the 3 elements synthesized in the Big Bang.[30] Though the amount of lithium generated in Big Bang nucleosynthesis is dependent upon the number of photons per baryon, for accepted values the lithium abundance can be calculated, and there is a "cosmological lithium discrepancy" in the Universe: older stars seem to have less lithium than they should, and some younger stars have far more. The lack of lithium in older stars is apparently caused by the "mixing" of lithium into the interior of stars, where it is destroyed.[31] Furthermore, lithium is produced in younger stars. Though it transmutes into two atoms of helium due to collision with a proton at temperatures above 2.4 million degrees Celsius (most stars easily attain this temperature in their interiors), lithium is more abundant than predicted in later-generation stars, for causes not yet completely understood.[13]
Though it was one of the three first elements (together with helium and hydrogen) to be synthesized in the Big Bang, lithium, together with beryllium and boron are markedly less abundant than other nearby elements. This is a result of the low temperature necessary to destroy lithium, and a lack of common processes to produce it.[32]
Lithium is also found in brown dwarf substellar objects and certain anomalous orange stars. Because lithium is present in cooler, less-massive brown dwarfs, but is destroyed in hotter red dwarf stars, its presence in the stars' spectra can be used in the "lithium test" to differentiate the two, as both are smaller than the Sun.[13][33][34] Certain orange stars can also contain a high concentration of lithium. Those orange stars found to have a higher than usual concentration of lithium (such as Centaurus X-4) orbit massive objects—neutron stars or black holes—whose gravity evidently pulls heavier lithium to the surface of a hydrogen-helium star, causing more lithium to be observed.[13]
## Terrestrial
Although lithium is widely distributed on Earth, it does not naturally occur in elemental form due to its high reactivity.[3] The total lithium content of seawater is very large and is estimated as 230 billion tonnes, where the element exists at a relatively constant concentration of 0.14 to 0.25 parts per million (ppm),[35][36] or 25 micromolar;[37]
higher concentrations approaching 7 ppm are found near hydrothermal vents.[36]
Estimates for crustal content range from 20 to 70 ppm by weight.[14] In keeping with its name, lithium forms a minor part of igneous rocks, with the largest concentrations in granites. Granitic pegmatites also provide the greatest abundance of lithium-containing minerals, with spodumene and petalite being the most commercially viable sources.[14] Another significant mineral of lithium is lepidolite.[38] A newer source for lithium is hectorite clay, the only active development of which is through the Western Lithium Corporation in the United States.[39] At 20 mg lithium per kg of Earth's crust,[40] lithium is the 25th most abundant element.
According to the Handbook of Lithium and Natural Calcium, "Lithium is a comparatively rare element, although it is found in many rocks and some brines, but always in very low concentrations. There are a fairly large number of both lithium mineral and brine deposits but only comparatively few of them are of actual or potential commercial value. Many are very small, others are too low in grade."[41]
One of the largest reserve base[note 2] of lithium is in the Salar de Uyuni area of Bolivia, which has 5.4 million tonnes. US Geological Survey, estimates that in 2010 Chile had the largest reserves by far (7.5 million tonnes)[42] and the highest annual production (8,800 tonnes). Other major suppliers include Australia, Argentina and China.
In June 2010, the New York Times reported that American geologists were conducting ground surveys on dry salt lakes in western Afghanistan believing that large deposits of lithium are located there. "Pentagon officials said that their initial analysis at one location in Ghazni Province showed the potential for lithium deposits as large as those of Bolivia, which now has the world's largest known lithium reserves."[43] These estimates are "based principally on old data, which was gathered mainly by the Soviets during their occupation of Afghanistan from 1979–1989" and "Stephen Peters, the head of the USGS's Afghanistan Minerals Project, said that he was unaware of USGS involvement in any new surveying for minerals in Afghanistan in the past two years. 'We are not aware of any discoveries of lithium,' he said."[44]
## Biological
Lithium is found in trace amount in numerous plants, plankton, and invertebrates, at concentrations of 69 to 5,760 parts per billion (ppb). In vertebrates the concentration is slightly lower, and nearly all vertebrate tissue and body fluids have been found to contain lithium ranging from 21 to 763 ppb.[36] Marine organisms tend to bioaccumulate lithium more than terrestrial ones.[45] It is not known whether lithium has a physiological role in any of these organisms,[36] but nutritional studies in mammals have indicated its importance to health, leading to a suggestion that it be classed as an essential trace element with an RDA of 1 mg/day.[46] Observational studies in Japan, reported in 2011, suggested that naturally occurring lithium in drinking water may increase human lifespan.[47]
# History of discovery and use
Petalite (LiAlSi4O10) was discovered in 1800 by the Brazilian chemist and statesman José Bonifácio de Andrada e Silva in a mine on the island of Utö, Sweden.[48][49][50] However, it was not until 1817 that Johan August Arfwedson, then working in the laboratory of the chemist Jöns Jakob Berzelius, detected the presence of a new element while analyzing petalite ore.[51][52][53] This element formed compounds similar to those of sodium and potassium, though its carbonate and hydroxide were less soluble in water and more alkaline.[54] Berzelius gave the alkaline material the name "lithion/lithina", from the Greek word λιθoς (transliterated as lithos, meaning "stone"), to reflect its discovery in a solid mineral, as opposed to potassium, which had been discovered in plant ashes, and sodium which was known partly for its high abundance in animal blood. He named the metal inside the material "lithium".[3][49][53]
Arfwedson later showed that this same element was present in the minerals spodumene and lepidolite.[49] In 1818, Christian Gmelin was the first to observe that lithium salts give a bright red color to flame.[49] However, both Arfwedson and Gmelin tried and failed to isolate the pure element from its salts.[49][53][55] It was not isolated until 1821, when William Thomas Brande obtained it by electrolysis of lithium oxide, a process that had previously been employed by the chemist Sir Humphry Davy to isolate the alkali metals potassium and sodium.[13][55][56][57] Brande also described some pure salts of lithium, such as the chloride, and, estimating that lithia (lithium oxide) contained about 55% metal, estimated the atomic weight of lithium to be around 9.8 g/mol (modern value ~6.94 g/mol).[58] In 1855, larger quantities of lithium were produced through the electrolysis of lithium chloride by Robert Bunsen and Augustus Matthiessen.[49] The discovery of this procedure henceforth led to commercial production of lithium, beginning in 1923, by the German company Metallgesellschaft AG, which performed an electrolysis of a liquid mixture of lithium chloride and potassium chloride.[49][59][60]
The production and use of lithium underwent several drastic changes in history. The first major application of lithium was in high-temperature lithium greases for aircraft engines or similar applications in World War II and shortly after. This use was supported by the fact that lithium-based soaps have a higher melting point than other alkali soaps, and are less corrosive than calcium based soaps. The small market for lithium soaps and the lubricating greases based upon them was supported by several small mining operations mostly in the United States.
The demand for lithium increased dramatically during the Cold War with the production of nuclear fusion weapons. Both lithium-6 and lithium-7 produce tritium when irradiated by neutrons, and are thus useful for the production of tritium by itself, as well as a form of solid fusion fuel used inside hydrogen bombs in the form of lithium deuteride. The United States became the prime producer of lithium in the period between the late 1950s and the mid-1980s. At the end, the stockpile of lithium was roughly 42,000 tonnes of lithium hydroxide. The stockpiled lithium was depleted in lithium-6 by 75%, which was enough to affect the measured atomic weight of lithium in many standardized chemicals, and even the atomic weight of lithium in some "natural sources" of lithium ion which had been "contaminated" by lithium salts discharged from isotope separation facilities, which had found its way into ground water.[29][61]
Lithium was used to decrease the melting temperature of glass and to improve the melting behavior of aluminium oxide when using the Hall-Héroult process.[62][62] These two uses dominated the market until the middle of the 1990s. After the end of the nuclear arms race the demand for lithium decreased and the sale of Department of Energy stockpiles on the open market further reduced prices.[61] But in the mid-1990s, several companies started to extract lithium from brine which proved to be a less expensive method than underground or even open-pit mining. Most of the mines closed or shifted their focus to other materials as only the ore from zoned pegmatites could be mined for a competitive price. For example, the US mines near Kings Mountain, North Carolina closed before the turn of the 21st century.
The use in lithium ion batteries increased the demand for lithium and became the dominant use in 2007.[63] With the surge of lithium demand in batteries in the 2000s, new companies have expanded brine extraction efforts to meet the rising demand.[64][65]
Lithium toxicity must be differentiated from other causes of hypercalcaemia
Lithium toxicity must be differentiated from other causes of diabetes insipidus.
# Production
Since the end of World War II lithium production has greatly increased. The metal is separated from other elements in igneous minerals such as those above. Lithium salts are extracted from the water of mineral springs, brine pools and brine deposits. The metal is produced electrolytically from a mixture of fused 55% lithium chloride and 45% potassium chloride at about 450o C.[76] In 1998 it was about 95 US$ / kg (or 43 US$/pound).[77]
Worldwide identified reserves of lithium in 2008 were estimated by the US Geological Survey as 13 million tonnes. Deposits of lithium are found in South America throughout the Andes mountain chain. Chile is the leading lithium producer, followed by Argentina. Both countries recover the lithium from brine pools. In the United States lithium is recovered from brine pools in Nevada.[11] However, half the world's known reserves are located in Bolivia, a nation sitting along the central eastern slope of the Andes.
In 2009 Bolivia was negotiating with Japanese, French, and Korean firms to begin extraction.[78] According to the US Geological Survey, Bolivia's Uyuni Desert has 5.4 million tonnes of lithium.[78][79] A newly discovered deposit in Wyoming's Rock Springs Uplift is estimated at 228,000 tons. Additional deposits in the same formation were extrapolated to be as much as 18 million tons.[80]
After an industry wide pricing reduction for lithium carbonate after the Great Financial Crisis, where major suppliers such as Sociedad Química y Minera (SQM) dropped pricing by 20%[81] in light of incoming lithium resource developers and to further defend their market position, pricing in 2012 scaled up due to increased lithium demand. A 2012 Business Week article outlined the existing oligopoly in the lithium space, "SQM, controlled by billionaire Julio Ponce, is the second-largest, followed by Rockwood, which is backed by Henry Kravis’s KKR & Co., and Philadelphia-based FMC." Global consumption may jump to 300,000 metric tons a year by 2020 from about 150,000 tons in 2012, as demand for lithium batteries has been growing at about 25 percent a year, outpacing the 4 percent to 5 percent overall gain in lithium[82]
A potential source is geothermal wells. Geothermal fluids carry leachates to the surface;[83] recovery of lithium has been demonstrated in the field.[84] As the lithium is separated by simple filtration techniques, the process and environmental costs are primarily that of the already-operating geothermal well; relative environmental impacts may thus be positive.[85]
There are differing opinions about the potential growth of lithium production. According to a 2011 study conducted at Lawrence Berkeley National Laboratory and the University of California Berkeley, the currently estimated reserve base of lithium should not be a limiting factor for large-scale battery production for electric vehicles, as the study estimated that on the order of 1 billion 40 kWh Li-based batteries could be built with current reserves.[86] Another 2011 study by researchers from the University of Michigan and Ford Motor Company found that there are sufficient lithium resources to support global demand until 2100, including the lithium required for the potential widespread use of hybrid electric, plug-in hybrid electric and battery electric vehicles. The study estimated global lithium reserves at 39 million tons, and total demand for lithium during the 90-year period analyzed at 12–20 million tons, depending on the scenarios regarding economic growth and recycling rates.[87]
However, another study concluded that "realistically achievable lithium carbonate production will be sufficient for only a small fraction of future PHEV and EV global market requirements", that "demand from the portable electronics sector will absorb much of the planned production increases in the next decade", and that "mass production of lithium carbonate is not environmentally sound, it will cause irreparable ecological damage to ecosystems that should be protected and that LiIon propulsion is incompatible with the notion of the 'Green Car'.
## Ceramics and glass
Lithium oxide is a widely used flux for processing silica, reducing the melting point and viscosity of the material and leading to glazes of improved physical properties including low coefficients for thermal expansion.[88] Lithium oxides are a component of ovenware. Worldwide, this is the single largest use for lithium compounds. Lithium carbonate (Li2CO3) is generally used in this application: upon heating it converts to the oxide.[89]
## Electrical and electronics
In the later years of the 20th century, owing to its high electrochemical potential, lithium became an important component of the electrolyte and of one of the electrodes in batteries. A typical lithium-ion battery can generate approximately 3 volts, compared with 2.1 volts for lead-acid or 1.5 volts for zinc-carbon cells. Because of its low atomic mass, it also has a high charge- and power-to-weight ratio. Lithium batteries are disposable (primary) batteries with lithium or its compounds as an anode.[90][91] Lithium batteries are not to be confused with lithium-ion batteries, which are high energy-density rechargeable batteries. Other rechargeable batteries include the lithium-ion polymer battery, lithium iron phosphate battery, and the nanowire battery.
## Lubricating greases
The third most common use of lithium is in greases. Lithium hydroxide is a strong base and, when heated with a fat, produces a soap made of lithium stearate. Lithium soap has the ability to thicken oils, and it is used to manufacture all-purpose, high-temperature lubricating greases.[11][92][93]
## Metallurgy
When used as a flux for welding or soldering, metallic lithium promotes the fusing of metals during the process and eliminates the forming of oxides by absorbing impurities. Its fusing quality is also important as a flux for producing ceramics, enamels and glass. Alloys of the metal with aluminium, cadmium, copper and manganese are used to make high-performance aircraft parts (see also Lithium-aluminium alloys).[94]
### Pyrotechnics
Lithium compounds are used as pyrotechnic colorants and oxidizers in red fireworks and flares.[11][95]
### Air purification
Lithium chloride and lithium bromide are hygroscopic and are used as desiccants for gas streams.[11] Lithium hydroxide and lithium peroxide are the salts most used in confined areas, such as aboard spacecraft and submarines, for carbon dioxide removal and air purification. Lithium hydroxide absorbs carbon dioxide from the air by forming lithium carbonate, and is preferred over other alkaline hydroxides for its low weight.
Lithium peroxide (Li2O2) in presence of moisture not only reacts with carbon dioxide to form lithium carbonate, but also releases oxygen.[96][97] The reaction is as follows:
Some of the aforementioned compounds, as well as lithium perchlorate, are used in oxygen candles that supply submarines with oxygen. These can also include small amounts of boron, magnesium, aluminum, silicon, titanium, manganese, and iron.[98]
### Optics
Lithium fluoride, artificially grown as crystal, is clear and transparent and often used in specialist optics for IR, UV and VUV (vacuum UV) applications. It has one of the lowest refractive indexes and the farthest transmission range in the deep UV of most common materials.[99] Finely divided lithium fluoride powder has been used for thermoluminescent radiation dosimetry (TLD): when a sample of such is exposed to radiation, it accumulates crystal defects which, when heated, resolve via a release of bluish light whose intensity is proportional to the absorbed dose, thus allowing this to be quantified.[100] Lithium fluoride is sometimes used in focal lenses of telescopes.[11][101]
The high non-linearity of lithium niobate also makes it useful in non-linear optics applications. It is used extensively in telecommunication products such as mobile phones and optical modulators, for such components as resonant crystals. Lithium applications are used in more than 60% of mobile phones.[102]
### Organic and polymer chemistry
Organolithium compounds are widely used in the production of polymer and fine-chemicals. In the polymer industry, which is the dominant consumer of these reagents, alkyl lithium compounds are catalysts/initiators.[103] in anionic polymerization of unfunctionalized olefins.[104][105][106] For the production of fine chemicals, organolithium compounds function as strong bases and as reagents for the formation of carbon-carbon bonds. Organolithium compounds are prepared from lithium metal and alkyl halides.[107]
Many other lithium compounds are used as reagents to prepare organic compounds. Some popular compounds include lithium aluminium hydride (LiAlH4), lithium triethylborohydride (LiBH(C2H5)3).
### Military applications
Metallic lithium and its complex hydrides, such as Li[AlH4], are used as high energy additives to rocket propellants.[13] Lithium aluminum hydride can also be used by itself as a solid fuel.[108]
The Mark 50 Torpedo stored chemical energy propulsion system (SCEPS) uses a small tank of sulfur hexafluoride gas which is sprayed over a block of solid lithium. The reaction generates heat which is used to generate steam. The steam propels the torpedo in a closed Rankine cycle.[109]
Lithium hydride containing lithium-6 is used in hydrogen bombs. In the bomb, it is placed around the core of an atomic bomb.[110]
## Nuclear
Lithium-6 is valued as a source material for tritium production and as a neutron absorber in nuclear fusion. Natural lithium contains about 7.5% lithium-6 from which large amounts of lithium-6 have been produced by isotope separation for use in nuclear weapons.[111] Lithium-7 gained interest for use in nuclear reactor coolants.[112]
Lithium deuteride was the fusion fuel of choice in early versions of the hydrogen bomb. When bombarded by neutrons, both 6Li and 7Li produce tritium — this reaction, which was not fully understood when hydrogen bombs were first tested, was responsible for the runaway yield of the Castle Bravo nuclear test. Tritium fuses with deuterium in a fusion reaction that is relatively easy to achieve. Although details remain secret, lithium-6 deuteride still apparently plays a role in modern nuclear weapons, as a fusion material.[113]
Lithium fluoride, when highly enriched in the lithium-7 isotope, forms the basic constituent of the fluoride salt mixture LiF-BeF2 used in liquid fluoride nuclear reactors. Lithium fluoride is exceptionally chemically stable and LiF-BeF2 mixtures have low melting points. In addition, 7Li, Be, and F are among the few nuclides with low enough thermal neutron capture cross-sections not to poison the fission reactions inside a nuclear fission reactor.[note 3][114]
In conceptualized nuclear fusion power plants, lithium will be used to produce tritium in magnetically confined reactors using deuterium and tritium as the fuel. Naturally occurring tritium is extremely rare, and must be synthetically produced by surrounding the reacting plasma with a 'blanket' containing lithium where neutrons from the deuterium-tritium reaction in the plasma will fission the lithium to produce more tritium:
Lithium is also used as a source for alpha particles, or helium nuclei. When 7Li is bombarded by accelerated protons 8Be is formed, which undergoes fission to form two alpha particles. This feat, called "splitting the atom" at the time, was the first fully man-made nuclear reaction. It was produced by Cockroft and Walton in 1932.[115][116] (Nuclear reactions and human-directed nuclear transmutation had been accomplished as early as 1917, but by using natural radioactive bombardment with alpha particles).
## Medicine
In the treatment of bipolar disorder, lithium compounds are used.[117] Lithium salts may also be helpful for related diagnoses, such as schizoaffective disorder and cyclic major depression. The active principle in these salts is the lithium ion Li+.[117] There have been suggestions of increased risk of developing Ebstein's cardiac anomaly in infants born to women taking lithium during the first trimester of pregnancy.[118]
# Precautions
Lithium is corrosive and requires special handling to avoid skin contact. Breathing lithium dust or lithium compounds (which are often alkaline) initially irritate the nose and throat, while higher exposure can cause a buildup of fluid in the lungs, leading to pulmonary edema. The metal itself is a handling hazard because of the caustic hydroxide produced when it is in contact with moisture. Lithium is safely stored in non-reactive compounds such as naphtha.[119]
## Regulation
Some jurisdictions limit the sale of lithium batteries, which are the most readily available source of lithium for ordinary consumers. Lithium can be used to reduce pseudoephedrine and ephedrine to methamphetamine in the Birch reduction method, which employs solutions of alkali metals dissolved in anhydrous ammonia.[120][121]
Carriage and shipment of some kinds of lithium batteries may be prohibited aboard certain types of transportation (particularly aircraft) because of the ability of most types of lithium batteries to fully discharge very rapidly when short-circuited, leading to overheating and possible explosion in a process called thermal runaway. Most consumer lithium batteries have thermal overload protection built-in to prevent this type of incident, or their design inherently limits short-circuit currents. Internal shorts have been known to develop due to manufacturing defects or damage to batteries that can lead to spontaneous thermal runaway.[122][123]
# Notes
- ↑ Densities for all the gaseous elements can be obtained at Airliquide.com
- ↑ Apendixes. By USGS definitions, reserve base "may encompass those parts of the resources that have a reasonable potential for becoming economically available within planning horizons beyond those that assume proven technology and current economics. The reserve base includes those resources that are currently economic (reserves), marginally economic (marginal reserves), and some of those that are currently subeconomic (subeconomic resources)."
- ↑ Beryllium and fluorine occur only as one isotope, 9Be and 19F respectively. These two, together with 7Li, as well as 2H, 11B, 15N, 209Bi, and the stable isotopes of C, and O, are the only nuclides with low enough thermal neutron capture cross sections aside from actinides to serve as major constituents of a molten salt breeder reactor fuel. | https://www.wikidoc.org/index.php/Eskalith | |
2177b94036162e2114315b2ed57f67da194307ff | wikidoc | Eugenol | Eugenol
Eugenol (C10H12O2), is an allyl chain-substituted guaiacol, i.e. 2-methoxy-4-(2-propenyl)phenol. Eugenol is a member of the allylbenzene class of chemical compounds. It is a clear to pale yellow oily liquid extracted from certain essential oils especially from clove oil, nutmeg, cinnamon, and bay leaf. It is slightly soluble in water and soluble in organic solvents. It has a pleasant, spicy, clove-like aroma.
# Modern uses
Eugenol is used in perfumeries, flavorings, essential oils and in medicine as a local antiseptic and anesthetic. It is a key ingredient in Indonesian kretek (clove) cigarettes. It was used in the production of isoeugenol for the manufacture of vanillin, though most vanillin is now produced from phenol or from lignin.
When mixed with zinc oxide, zinc oxide eugenol forms which has restorative and prosthodontic applications in dentistry.
Eugenol derivatives or methoxyphenol derivatives in wider classification are used in perfumery and flavoring. They are used in formulating insect attractants and UV absorbers, analgesics, biocides and antiseptics. They are also used in manufacturing stabilizers and antioxidants for plastics and rubbers. Although attempts have been made to develop eugenol derivatives for intravenous injection, the toxicity of propanidid and G.29.505 in human patients was not acceptable. Clove oil is growing in popularity as an anaesthetic for use on aquarium fish.
Eugenol is also used clandestinely for the synthesis of phenethylamines (like MDMA).
It is one of many compounds that is attractive to males of various species of orchid bees, who apparently gather the chemical to synthesize pheromones; it is commonly used as bait to attract and collect these bees for study.
# Toxicity
Overdose is possible, causing a wide range of symptoms from blood in the patient's urine, to convulsions, diarrhea, nausea, unconsciousness, dizziness, or rapid heartbeat.
Eugenol may cause allergic contact dermatitis with the skin.
# Health & Safety information
Eugenol should be avoided by people with perfume allergy. | Eugenol
Template:Chembox new
Eugenol (C10H12O2), is an allyl chain-substituted guaiacol, i.e. 2-methoxy-4-(2-propenyl)phenol. Eugenol is a member of the allylbenzene class of chemical compounds. It is a clear to pale yellow oily liquid extracted from certain essential oils especially from clove oil, nutmeg, cinnamon, and bay leaf. It is slightly soluble in water and soluble in organic solvents. It has a pleasant, spicy, clove-like aroma.
# Modern uses
Eugenol is used in perfumeries, flavorings, essential oils and in medicine as a local antiseptic and anesthetic.[1] It is a key ingredient in Indonesian kretek (clove) cigarettes. It was used in the production of isoeugenol for the manufacture of vanillin, though most vanillin is now produced from phenol or from lignin.
When mixed with zinc oxide, zinc oxide eugenol forms which has restorative and prosthodontic applications in dentistry.
Eugenol derivatives or methoxyphenol derivatives in wider classification are used in perfumery and flavoring. They are used in formulating insect attractants and UV absorbers, analgesics, biocides and antiseptics. They are also used in manufacturing stabilizers and antioxidants for plastics and rubbers. Although attempts have been made to develop eugenol derivatives for intravenous injection, the toxicity of propanidid and G.29.505[2] in human patients was not acceptable. Clove oil is growing in popularity as an anaesthetic for use on aquarium fish.
Eugenol is also used clandestinely for the synthesis of phenethylamines (like MDMA).
It is one of many compounds that is attractive to males of various species of orchid bees, who apparently gather the chemical to synthesize pheromones; it is commonly used as bait to attract and collect these bees for study.[3]
# Toxicity
Overdose is possible, causing a wide range of symptoms from blood in the patient's urine, to convulsions, diarrhea, nausea, unconsciousness, dizziness, or rapid heartbeat.
Eugenol may cause allergic contact dermatitis with the skin.
# Health & Safety information
Eugenol should be avoided by people with perfume allergy[4]. | https://www.wikidoc.org/index.php/Eugenol | |
c27f18c66df7da5528a918c6ed859220857b17bd | wikidoc | Melanin | Melanin
Melanin is a class of compounds found in the plant, animal and protista kingdoms, where it serves predominantly as a pigment. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole (also known as hydroquinone), dihydroxyindole carboxylic acid, and their reduced forms. Another common form of melanin is pheomelanin, a red-brown polymer of benzothiazine units largely responsible for red hair and freckles. The presence of melanin in the archaea and bacteria kingdoms is an issue of ongoing debate amongst researchers in the field.
The increased production of melanin in human skin is called melanogenesis. It is stimulated by the DNA damages that are caused by UVB-radiation, and it leads to a delayed development of a tan. This melanogenesis-based tan takes more time to develop, but it is long lasting.
The photochemical properties of melanin make it an excellent photoprotectant. It absorbs harmful UV-radiation and transforms the energy into harmless amounts of heat through a process called "ultrafast internal conversion". This property enables melanin to dissipate more than 99.9% of the absorbed UV radiation as heat and it keeps the generation of free radicals at a minimum (see photoprotection). This prevents the indirect DNA damage which is responsible for the formation of malignant melanoma.
# Melanin in humans
In humans, melanin is the primary determinant of human skin color and also found in hair, the pigmented tissue underlying the iris, the medulla and zona reticularis of the adrenal gland, the stria vascularis of the inner ear, and in pigment-bearing neurons within areas of the brainstem, such as the locus ceruleus and the substantia nigra.
Dermal melanin is produced by melanocytes, which are found in the stratum basale of the epidermis. Although human beings generally possess a similar concentration of melanocytes in their skin, the melanocytes in some individuals and ethnic groups more frequently or less frequently express the melanin-producing genes, thereby conferring a greater or lesser concentration of skin melanin. Some individual animals and humans have very little or no melanin in their bodies, a condition known as albinism.
Because melanin is an aggregate of smaller component molecules, there are a number of different types of melanin with differing proportions and bonding patterns of these component molecules. Both pheomelanin and eumelanin are found in human skin and hair, but eumelanin is the most abundant melanin in humans, as well as the form most likely to be deficient in albinism.
Eumelanin polymers have long been thought to comprise numerous cross-linked 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) polymers; recent research into the electrical properties of eumelanin, however, has indicated that it may consist of more basic oligomers adhering to one another by some other mechanism. Thus, the precise nature of eumelanin's molecular structure is once again the object of study. Eumelanin is found in hair and skin, and colors hair grey, black, yellow, and brown. In humans, it is more abundant in peoples with dark skin.
There are two different types of eumelanin, which are distinguished from each other by their
pattern of polymer bonds. The two types are black eumelanin and brown eumelanin, with black melanin being darker than brown. Black eumelanin is in mostly non-Europeans and aged Europeans, while brown eumelanin is in mostly young Europeans.
A small amount of black eumelanin in the absence of other pigments causes grey hair.
A small amount of brown eumelanin in the absence of other pigments causes yellow (blond) color hair.
Pheomelanin is also found in hair and skin and is both in lighter skinned humans and darker skinned humans. In general women have more pheomelanin than men, and thus women's skin is generally redder than men's. Pheomelanin imparts a pink to red hue and, thus, is found in particularly large quantities in red hair. Pheomelanin is particularly concentrated in the lips, nipples, glans of the penis, and vagina. Pheomelanin also may become carcinogenic when exposed to the ultraviolet rays of the sun. Chemically, pheomelanin differs from eumelanin in that its oligomer structure incorporates benzothiazine units which are produced instead of DHI and DHICA when the amino acid L-cysteine is present.
Neuromelanin is the dark pigment present in pigment bearing neurons of four deep brain nuclei: the substantia nigra (in Latin, literally "black substance") - Pars Compacta part, the locus ceruleus ("blue spot"), the dorsal motor nucleus of the vagus nerve (cranial nerve X), and the median raphe nucleus of the pons. Both the substantia nigra and locus ceruleus can be easily identified grossly at the time of autopsy due to their dark pigmentation. In humans, these nuclei are not pigmented at the time of birth, but develop pigmentation during maturation to adulthood. Although the functional nature of neuromelanin is unknown in the brain, it may be a byproduct of the synthesis of monoamine neurotransmitters for which the pigmented neurons are the only source. The loss of pigmented neurons from specific nuclei is seen in a variety of neurodegenerative diseases. In Parkinson's disease there is massive loss of dopamine producing pigmented neurons in the substantia nigra. A common finding in advanced Alzheimer's disease is almost complete loss of the norepinephrine producing pigmented neurons of the locus ceruleus. Neuromelanin has been detected in primates and in carnivores such as cats and dogs.
# Melanin in other organisms
Melanins have very diverse roles and functions in various organisms. A form of eumelanin makes up the ink used by Cuttlefish as a defence mechanism against predators. Melanins also protect microorganisms, such as bacteria and fungi, against stresses that involve cell damage by solar UV radiation or generation of reactive oxygen species. These include high temperature as well as chemical (e.g. heavy metals and oxidizing agents), and biochemical (e.g., host defenses against invading microbes) stresses. Therefore, in many pathogenic microbes (for example, in Cryptococcus neoformans, a fungus) melanins appear to play important roles in virulence and pathogenicity by protecting the microbe against immune responses of its host. A potentially novel role of melanin as a photosynthetic pigment in some fungi, enabling them to capture gamma rays and harness its energy for growth has recently been described. (See radiotrophic fungus) In invertebrates, a major aspect of the innate immune defense system against invading pathogens involves melanin. Within minutes after infection, the microbe is encapsulated within melanin (melanization), and the generation of free radical byproducts during the formation of this capsule is thought to aid in their killing.
# Biosynthetic pathways
The first step of the biosynthetic pathway for both eumelanins and pheomelanins is catalysed by tyrosinase:
Dopaquinone can combine with cysteine by two pathways to benzothiazines and pheomelanins
Alternatively, dopaquinone can be converted to leucodopachrome and follow two more pathways to the eumelanins
Microscopic appearance
Under the microscope melanin is brown, non-refractile and finely granular with individual granules having a diameter of less than 800 nanometers. This differentiates melanin from common blood breakdown pigments which are larger, chunky and refractile and range in color from green to yellow or red-brown. In heavily pigmented lesions, dense aggregates of melanin can obscure histologic detail. A dilute solution of potassium permanganate is an effective melanin bleach.
# Melanin deficiency in genetic disorders and disease states
Melanin deficiency has been connected for some time with various genetic abnormalities and disease states.
There are approximately ten different types of oculocutaneous albinism, which is mostly an autosomal recessive disorder. Certain ethnicities have higher incidences of different forms. For example, the most common type, called oculocutaneous albinism type 2 (OCA2), is especially frequent among people of black African descent. It is an autosomal recessive disorder characterized by a congenital reduction or absence of melanin pigment in the skin, hair and eyes. The estimated frequency of OCA2 among African-Americans is 1 in 10,000, which contrasts with a frequency of 1 in 36,000 in white Americans. In some African nations, the frequency of the disorder is even higher, ranging from 1 in 2,000 to 1 in 5,000. Another form of Albinism, the "yellow oculocutaneous albinism", appears to be more prevalent among the Amish, who are of primarily Swiss and German ancestry. People with this IB variant of the disorder commonly have white hair and skin at birth, but rapidly develop normal skin pigmentation in infancy.
Ocular albinism affects not only eye pigmentation, but visual acuity, as well. People with albinism typically test poorly, within the 20/60 to 20/400 range. Additionally, two forms of albinism, with approximately 1 in 2700 most prevalent among people of Puerto Rican origin, are associated with mortality beyond melanoma-related deaths.
Mortality also is increased in patients with Hermansky-Pudlak syndrome and Chediak-Higashi syndrome. Patients with Hermansky-Pudlak syndrome have a bleeding diathesis secondary to platelet dysfunction and also experience restrictive lung disease (pulmonary fibrosis), inflammatory bowel disease, cardiomyopathy, and renal disease. Patients with Chediak-Higashi syndrome are susceptible to infection and also can develop lymphofollicular malignancy.
The role that melanin deficiency plays in such disorders remains under study.
The connection between albinism and deafness has been well known, though poorly understood, for more than a century-and-a-half. In his 1859 treatise On the Origin of Species, Charles Darwin observed that "cats which are entirely white and have blue eyes are generally deaf". In humans, hypopigmentation and deafness occur together in the rare Waardenburg's syndrome, predominantly observed among the Hopi in North America. The incidence of albinism in Hopi Indians has been estimated as approximately 1 in 200 individuals. Interestingly, similar patterns of albinism and deafness have been found in other mammals, including dogs and rodents. However, a lack of melanin per se does not appear to be directly responsible for deafness associated with hypopigmentation, as most individuals lacking the enzymes required to synthesize melanin have normal auditory function. Instead the absence of melanocytes in the stria vascularis of the inner ear results in cochlear impairment, though why this is is not fully understood. It may be that melanin, the best sound absorbing material known, plays some protective function. Alternately, melanin may affect development, as Darwin suggests.
In Parkinson's disease, a disorder that affects neuromotor functioning, there is decreased neuromelanin in the substantia nigra as consequence of specific dropping out of dopaminergic pigmented neurons. This results in diminished dopamine synthesis. While no correlation between race and the level of neuromelanin in the substantia nigra has been reported, the significantly lower incidence of Parkinson's in blacks than in whites has "prompt some to suggest that cutaneous melanin might somehow serve to protect the neuromelanin in substantia nigra from external toxins.". Also see Nicolaus review article on the function of neuromalanins
In addition to melanin deficiency, the molecular weight of the melanin polymer may be decreased due to various factors such as oxidative stress, exposure to light, perturbation in its association with melanosomal matrix proteins, changes in pH or in local concentrations of metal ions. A decreased molecular weight or a decrease in the degree of polymerization of ocular melanin has been proposed to turn the normally anti-oxidant polymer into a pro-oxidant. In its pro-oxidant state, melanin has been suggested to be involved in the causation and progression of macular degeneration and melanoma. (Ref: Pigment cell Res. 2001; volume 14: pages 148-154. "Redox regulation in human melanocytes and melanoma")
Higher eumelanin levels also can be a disadvantage, however, beyond a higher disposition toward vitamin D deficiency. Dark skin is a complicating factor in the laser removal of port-wine stains. Effective in treating white skin, lasers generally are less successful in removing port-wine stains in people of Asian or African descent. Higher concentrations of melanin in darker-skinned individuals simply diffuse and absorb the laser radiation, inhibiting light absorption by the targeted tissue. Melanin similarly can complicate laser treatment of other dermatological conditions in people with darker skin.
Freckles and moles are formed where there is a localized concentration of melanin in the skin. They are highly associated with pale skin.
## Melanin and human adaptation
Melanocytes insert granules of melanin into specialized cellular vesicles called melanosomes. These are then transferred into the other skin cells of the human epidermis. The melanosomes in each recipient cell accumulate atop the cell nucleus, where they protect the nuclear DNA from mutations caused by the ionizing radiation of the sun's ultraviolet rays. People whose ancestors lived for long periods in the regions of the globe near the equator generally have larger quantities of eumelanin in their skins. This makes their skins brown or black and protects them against high levels of exposure to the sun, which more frequently results in melanomas in lighter skinned people.
With humans, exposure to sunlight stimulates the skin to produce vitamin D. Because high levels of cutaneous melanin act as a natural sun screen, dark skin can be a risk factor for vitamin D deficiency.
In the United Kingdom, which lies at a northern latitude, descendants of the Britons have white skin. When their skin is exposed to the meager sunlight, the scant amount of melanin their skin produces is unable to block the sunlight. Therefore, their bodies are able to make Vitamin D with the help of sunlight. Vitamin D, a vitamin found in fish oil, is necessary to prevent rickets, a bone disease caused by too little calcium.
In contrast, in Sub-Saharan Africa, which is near the equator, humans with a higher concentration of melanin absorb more intense sunlight to make Vitamin D. Africans visiting the United Kingdom during the Industrial Revolution developed symptoms of rickets, such as retarded growth, bowed legs, and fractures because sunlight at that latitude was insufficient for their melanin levels.
Fortunately, in 1930, Vitamin D was discovered and dispensed as a supplement to add to the diet. Now many common foods like milk and bread are Vitamin D fortified.
The most recent scientific evidence indicates that all humans evolved in Africa, then populated the rest of the world through successive radiations. It is most likely that the first people had relatively large numbers of eumelanin producing melanocytes and, accordingly, darker skin (as displayed by the indigenous people of Africa, today). As some of these original peoples migrated and settled in areas of Asia and Europe, the selective pressure for eumelanin production decreased in climates where radiation from the sun was less intense. Thus variations in genes involved in melanin production began to appear in the population, resulting in lighter hair and skin in humans residing at northern latitudes. Studies have been carried out to determine whether these changes were due to genetic drift or positive selection, perhaps driven by requirement for vitamin D. Of the two common gene variants known to be associated with pale human skin, Mc1r does not appear to have undergone positive selection, while SLC24A5 has.
As with peoples who migrated northward, those with light skin who migrate southward acclimatize to the much stronger solar radiation. Most people's skin darkens when exposed to UV light, giving them more protection when it is needed. This is the physiological purpose of sun tanning. Dark-skinned people, who produce more skin-protecting eumelanin, have a greater protection against sunburn and the development of melanoma, a potentially deadly form of skin cancer, as well as other health problems related to exposure to strong solar radiation, including the photodegradation of certain vitamins such as riboflavins, carotenoids, tocopherol, and folate.
Melanin in the eyes helps protect them from ultraviolet and high-frequency visible light; people with blue eyes are more at risk for sun-related eye problems. Further, the ocular lens yellows with age, providing added protection. However, the lens also becomes more rigid with age, losing most of its accommodation — the ability to change shape to focus from far to near — a detriment due probably to protein crosslinking caused by UV exposure.
Recent research by J.D. Simon et al. (Pigment Cell Research, 2004, 17: 262-269) suggests that melanin may serve a protective role other than photoprotection. Melanin is able to effectively ligate metal ions through its carboxylate and phenolic hydroxyl groups, in many cases much more efficiently than the powerful chelating ligand ethylenediaminetetraacetate (EDTA). It may thus serve to sequester potentially toxic metal ions, protecting the rest of the cell. This hypothesis is supported by the fact that the loss of neuromelanin observed in Parkinson's disease is accompanied by an increase in iron levels in the brain.
# Physical properties and technological applications
Melanins are "rigid-backbone" conductive polymers composed of polyacetylene, polypyrrole, and polyaniline "Blacks" and their mixed copolymers. The simplist melanin is polyacetylene, from which all others derive. Some fungal melanins are pure polyacetylene.
In 1963, DE Weiss and coworkers reported high electrical conductivity in a melanin, iodine-doped and oxidized polypyrrole "Black". They achieved the quite high conductivity of 1 Ohm/cm. A decade later, John McGinness, and coworkers reported a high conductivity "ON" state in a voltage-controlled solid-state threshold switch made with DOPA melanin . Further, this material emitted a flash of light—electroluminescence—when it switched. Melanin also shows negative resistance, a classic property of electronically-active conductive polymers. Likewise, melanin is the best sound-absorbing material known due to strong electron-phonon coupling. This may be related to melanin's presence in the inner ear.
These early discoveries were "lost" until the recent emergence of such melanins in device applications, particularly electroluminescent displays. In 2000, the Nobel Prize in Chemistry was awarded to three scientists for their subsequent 1977 (re)discovery and development of such conductive organic polymers. In an essential reprise of Weiss et al's work, these polymers were oxidized, iodine-doped "polyacetylene black" melanins. There is no evidence the Nobel committee was aware of Weiss et als almost identical prior report of passive high conductivity in iodinated polypyrrole black or of switching and high electrical conductivity in DOPA melanin and related organic semiconductors. The melanin organic electronic device is now in the Smithsonian Institution's National Museum of American History's "Smithsonian Chips" collection of historic solid-state electronic devices.
Melanin influences neural activity and mediates the conduction of radiation, light, heat and kinetic energy. As such, it is the subject of intense interest in biotech research and development, most notably in organic electronics (sometimes called "plastic electronics") and nanotechnology, where dopants are used to dramatically boost melanin conductivity. Pyrrole black and acetylene black are the most commonly studied organic semiconductors.
Although synthetic melanin (commonly referred to as BSM, or "black synthetic matter") is made up of 3-6 oligomeric units linked together—the so-called "protomolecule"—there is no evidence that naturally occurring biopolymer (BCM, for "black cell matter") mimics this structure. However, since there is no reason to believe that natural melanin does not belong to the category of the polyarenes and polycationic polyenes, like pyrrol black and acetylene black, it is necessary to review all the chemical and biological analytic data gathered to date in the study of natural melanins (eumelanins, pheomelanins, allomelanins)."
Evidence exists in support of a highly cross-linked heteropolymer bound covalently to matrix scaffolding melanoproteins (Eur. J. Biochem. 1995; 232: 159-164 "Interaction of melanosomal proteins with melanin). It has been proposed that the ability of melanin to act as an antioxidant is directly proportional to its degree of polymerization or molecular weight (Ophthalmic research, 2005, 37: 136-141 "Melanin aggregation and polymerization: possible implications in age related macular degeneration"). Suboptimal conditions for the effective polymerization of melanin monomers may lead to formation of lower-molecular-weight, pro-oxidant melanin that is has been implicated in the causation and progression of macular degeneration and melanoma. (Clinical Cancer Res. 2004; 10: 2581-2583 "Etiologic pathogenesis of melanoma: a unifying hypothesis for the missing attributable risk"). Signaling pathways that upregulate melanization in the retinal pigment epithelium (RPE) also may be implicated in the downregulation of rod outer segment phagocytosis by the RPE. This phenomenon has been attributed in part to foveal sparing in macular degeneration. (Mol. Vis. 2005; 11: 482-490 "Melanization and phagocytosis: implications for age-related macular degeneration).
# Melanin-based bias in human societies
When skin pigmentation as a characteristic of race is linked to social status or other human attributes, this phenomenon is known as racialism. Many people and societies overlay racialism with racist perceptions and systems which arbitrarily assign to groups of people a status of inherent superiority or inferiority, privilege or disadvantage based on skin color or racial classification. Apartheid-era South Africa is an example of a white supremacist society based on a system of stratification of power and privilege by skin color, as well as racial admixture. Similar examples can be found in India's caste system; Brazil's highly socially color-stratified society; and, in the U.S., segregation and institutional racism on the part of white-controlled institutions, and internal "color consciousness" on the part of members of some ethnic minorities. Because of the pervasive influence of white supremacist values worldwide, prejudice against people with more highly pigmented skin is the most pervasive form of color bias. Conversely, black supremacy is a far less pervasive phenomenon. Many other societies remain informally divided on the basis of skin color and, often, related ethnicity. (See also colonialism, Nazism and institutional racism.)
Illogical presumptions about people with regard to hair color are far less common than skin-color bias, have far fewer and less serious real-world implications, and are more often applied to women than to men. Common stereotypes in the West are dumb blondes, hot-tempered redheads and vixen brunettes. | Melanin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]
Melanin is a class of compounds found in the plant, animal and protista kingdoms, where it serves predominantly as a pigment. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole (also known as hydroquinone), dihydroxyindole carboxylic acid, and their reduced forms. Another common form of melanin is pheomelanin, a red-brown polymer of benzothiazine units largely responsible for red hair and freckles. The presence of melanin in the archaea and bacteria kingdoms is an issue of ongoing debate amongst researchers in the field.
The increased production of melanin in human skin is called melanogenesis. It is stimulated by the DNA damages that are caused by UVB-radiation,[1] and it leads to a delayed development of a tan. This melanogenesis-based tan takes more time to develop, but it is long lasting.[2]
The photochemical properties of melanin make it an excellent photoprotectant. It absorbs harmful UV-radiation and transforms the energy into harmless amounts of heat through a process called "ultrafast internal conversion". This property enables melanin to dissipate more than 99.9% of the absorbed UV radiation as heat[3] and it keeps the generation of free radicals at a minimum (see photoprotection). This prevents the indirect DNA damage which is responsible for the formation of malignant melanoma.
# Melanin in humans
In humans, melanin is the primary determinant of human skin color and also found in hair, the pigmented tissue underlying the iris, the medulla and zona reticularis of the adrenal gland, the stria vascularis of the inner ear, and in pigment-bearing neurons within areas of the brainstem, such as the locus ceruleus and the substantia nigra.
Dermal melanin is produced by melanocytes, which are found in the stratum basale of the epidermis. Although human beings generally possess a similar concentration of melanocytes in their skin, the melanocytes in some individuals and ethnic groups more frequently or less frequently express the melanin-producing genes, thereby conferring a greater or lesser concentration of skin melanin. Some individual animals and humans have very little or no melanin in their bodies, a condition known as albinism.
Because melanin is an aggregate of smaller component molecules, there are a number of different types of melanin with differing proportions and bonding patterns of these component molecules. Both pheomelanin and eumelanin are found in human skin and hair, but eumelanin is the most abundant melanin in humans, as well as the form most likely to be deficient in albinism.
Eumelanin polymers have long been thought to comprise numerous cross-linked 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) polymers; recent research into the electrical properties of eumelanin, however, has indicated that it may consist of more basic oligomers adhering to one another by some other mechanism. Thus, the precise nature of eumelanin's molecular structure is once again the object of study. Eumelanin is found in hair and skin, and colors hair grey, black, yellow, and brown. In humans, it is more abundant in peoples with dark skin.
There are two different types of eumelanin, which are distinguished from each other by their
pattern of polymer bonds. The two types are black eumelanin and brown eumelanin, with black melanin being darker than brown. Black eumelanin is in mostly non-Europeans and aged Europeans, while brown eumelanin is in mostly young Europeans.
A small amount of black eumelanin in the absence of other pigments causes grey hair.
A small amount of brown eumelanin in the absence of other pigments causes yellow (blond) color hair.
Pheomelanin is also found in hair and skin and is both in lighter skinned humans and darker skinned humans. In general women have more pheomelanin than men, and thus women's skin is generally redder than men's. Pheomelanin imparts a pink to red hue and, thus, is found in particularly large quantities in red hair. Pheomelanin is particularly concentrated in the lips, nipples, glans of the penis, and vagina.[4] Pheomelanin also may become carcinogenic when exposed to the ultraviolet rays of the sun. Chemically, pheomelanin differs from eumelanin in that its oligomer structure incorporates benzothiazine units which are produced instead of DHI and DHICA when the amino acid L-cysteine is present.
Neuromelanin is the dark pigment present in pigment bearing neurons of four deep brain nuclei: the substantia nigra (in Latin, literally "black substance") - Pars Compacta part, the locus ceruleus ("blue spot"), the dorsal motor nucleus of the vagus nerve (cranial nerve X), and the median raphe nucleus of the pons. Both the substantia nigra and locus ceruleus can be easily identified grossly at the time of autopsy due to their dark pigmentation. In humans, these nuclei are not pigmented at the time of birth, but develop pigmentation during maturation to adulthood. Although the functional nature of neuromelanin is unknown in the brain, it may be a byproduct of the synthesis of monoamine neurotransmitters for which the pigmented neurons are the only source. The loss of pigmented neurons from specific nuclei is seen in a variety of neurodegenerative diseases. In Parkinson's disease there is massive loss of dopamine producing pigmented neurons in the substantia nigra. A common finding in advanced Alzheimer's disease is almost complete loss of the norepinephrine producing pigmented neurons of the locus ceruleus. Neuromelanin has been detected in primates and in carnivores such as cats and dogs.
# Melanin in other organisms
Melanins have very diverse roles and functions in various organisms. A form of eumelanin makes up the ink used by Cuttlefish as a defence mechanism against predators. Melanins also protect microorganisms, such as bacteria and fungi, against stresses that involve cell damage by solar UV radiation or generation of reactive oxygen species. These include high temperature as well as chemical (e.g. heavy metals and oxidizing agents), and biochemical (e.g., host defenses against invading microbes) stresses.[5] Therefore, in many pathogenic microbes (for example, in Cryptococcus neoformans, a fungus) melanins appear to play important roles in virulence and pathogenicity by protecting the microbe against immune responses of its host. A potentially novel role of melanin as a photosynthetic pigment in some fungi, enabling them to capture gamma rays[6] and harness its energy for growth has recently been described.[7] (See radiotrophic fungus) In invertebrates, a major aspect of the innate immune defense system against invading pathogens involves melanin. Within minutes after infection, the microbe is encapsulated within melanin (melanization), and the generation of free radical byproducts during the formation of this capsule is thought to aid in their killing.[8]
# Biosynthetic pathways
The first step of the biosynthetic pathway for both eumelanins and pheomelanins is catalysed by tyrosinase:
Dopaquinone can combine with cysteine by two pathways to benzothiazines and pheomelanins
Alternatively, dopaquinone can be converted to leucodopachrome and follow two more pathways to the eumelanins
Microscopic appearance
Under the microscope melanin is brown, non-refractile and finely granular with individual granules having a diameter of less than 800 nanometers. This differentiates melanin from common blood breakdown pigments which are larger, chunky and refractile and range in color from green to yellow or red-brown. In heavily pigmented lesions, dense aggregates of melanin can obscure histologic detail. A dilute solution of potassium permanganate is an effective melanin bleach.
# Melanin deficiency in genetic disorders and disease states
Melanin deficiency has been connected for some time with various genetic abnormalities and disease states.
There are approximately ten different types of oculocutaneous albinism, which is mostly an autosomal recessive disorder. Certain ethnicities have higher incidences of different forms. For example, the most common type, called oculocutaneous albinism type 2 (OCA2), is especially frequent among people of black African descent. It is an autosomal recessive disorder characterized by a congenital reduction or absence of melanin pigment in the skin, hair and eyes. The estimated frequency of OCA2 among African-Americans is 1 in 10,000, which contrasts with a frequency of 1 in 36,000 in white Americans.[9] In some African nations, the frequency of the disorder is even higher, ranging from 1 in 2,000 to 1 in 5,000.[10] Another form of Albinism, the "yellow oculocutaneous albinism", appears to be more prevalent among the Amish, who are of primarily Swiss and German ancestry. People with this IB variant of the disorder commonly have white hair and skin at birth, but rapidly develop normal skin pigmentation in infancy.[10]
Ocular albinism affects not only eye pigmentation, but visual acuity, as well. People with albinism typically test poorly, within the 20/60 to 20/400 range. Additionally, two forms of albinism, with approximately 1 in 2700 most prevalent among people of Puerto Rican origin, are associated with mortality beyond melanoma-related deaths.
Mortality also is increased in patients with Hermansky-Pudlak syndrome and Chediak-Higashi syndrome. Patients with Hermansky-Pudlak syndrome have a bleeding diathesis secondary to platelet dysfunction and also experience restrictive lung disease (pulmonary fibrosis), inflammatory bowel disease, cardiomyopathy, and renal disease. Patients with Chediak-Higashi syndrome are susceptible to infection and also can develop lymphofollicular malignancy.[10]
The role that melanin deficiency plays in such disorders remains under study.
The connection between albinism and deafness has been well known, though poorly understood, for more than a century-and-a-half. In his 1859 treatise On the Origin of Species, Charles Darwin observed that "cats which are entirely white and have blue eyes are generally deaf".[11] In humans, hypopigmentation and deafness occur together in the rare Waardenburg's syndrome, predominantly observed among the Hopi in North America.[12] The incidence of albinism in Hopi Indians has been estimated as approximately 1 in 200 individuals. Interestingly, similar patterns of albinism and deafness have been found in other mammals, including dogs and rodents. However, a lack of melanin per se does not appear to be directly responsible for deafness associated with hypopigmentation, as most individuals lacking the enzymes required to synthesize melanin have normal auditory function.[13] Instead the absence of melanocytes in the stria vascularis of the inner ear results in cochlear impairment,[14] though why this is is not fully understood. It may be that melanin, the best sound absorbing material known, plays some protective function. Alternately, melanin may affect development, as Darwin suggests.
In Parkinson's disease, a disorder that affects neuromotor functioning, there is decreased neuromelanin in the substantia nigra as consequence of specific dropping out of dopaminergic pigmented neurons. This results in diminished dopamine synthesis. While no correlation between race and the level of neuromelanin in the substantia nigra has been reported, the significantly lower incidence of Parkinson's in blacks than in whites has "prompt[ed] some to suggest that cutaneous melanin might somehow serve to protect the neuromelanin in substantia nigra from external toxins."[15]. Also see Nicolaus[16] review article on the function of neuromalanins
In addition to melanin deficiency, the molecular weight of the melanin polymer may be decreased due to various factors such as oxidative stress, exposure to light, perturbation in its association with melanosomal matrix proteins, changes in pH or in local concentrations of metal ions. A decreased molecular weight or a decrease in the degree of polymerization of ocular melanin has been proposed to turn the normally anti-oxidant polymer into a pro-oxidant. In its pro-oxidant state, melanin has been suggested to be involved in the causation and progression of macular degeneration and melanoma. (Ref: Pigment cell Res. 2001; volume 14: pages 148-154. "Redox regulation in human melanocytes and melanoma")
Higher eumelanin levels also can be a disadvantage, however, beyond a higher disposition toward vitamin D deficiency. Dark skin is a complicating factor in the laser removal of port-wine stains. Effective in treating white skin, lasers generally are less successful in removing port-wine stains in people of Asian or African descent. Higher concentrations of melanin in darker-skinned individuals simply diffuse and absorb the laser radiation, inhibiting light absorption by the targeted tissue. Melanin similarly can complicate laser treatment of other dermatological conditions in people with darker skin.
Freckles and moles are formed where there is a localized concentration of melanin in the skin. They are highly associated with pale skin.
## Melanin and human adaptation
Melanocytes insert granules of melanin into specialized cellular vesicles called melanosomes. These are then transferred into the other skin cells of the human epidermis. The melanosomes in each recipient cell accumulate atop the cell nucleus, where they protect the nuclear DNA from mutations caused by the ionizing radiation of the sun's ultraviolet rays. People whose ancestors lived for long periods in the regions of the globe near the equator generally have larger quantities of eumelanin in their skins. This makes their skins brown or black and protects them against high levels of exposure to the sun, which more frequently results in melanomas in lighter skinned people.
With humans, exposure to sunlight stimulates the skin to produce vitamin D. Because high levels of cutaneous melanin act as a natural sun screen, dark skin can be a risk factor for vitamin D deficiency.
In the United Kingdom, which lies at a northern latitude, descendants of the Britons have white skin. When their skin is exposed to the meager sunlight, the scant amount of melanin their skin produces is unable to block the sunlight. Therefore, their bodies are able to make Vitamin D with the help of sunlight. Vitamin D, a vitamin found in fish oil, is necessary to prevent rickets, a bone disease caused by too little calcium.
In contrast, in Sub-Saharan Africa, which is near the equator, humans with a higher concentration of melanin absorb more intense sunlight to make Vitamin D. Africans visiting the United Kingdom during the Industrial Revolution developed symptoms of rickets, such as retarded growth, bowed legs, and fractures because sunlight at that latitude was insufficient for their melanin levels.
Fortunately, in 1930, Vitamin D was discovered and dispensed as a supplement to add to the diet. Now many common foods like milk and bread are Vitamin D fortified.
The most recent scientific evidence indicates that all humans evolved in Africa, then populated the rest of the world through successive radiations. It is most likely that the first people had relatively large numbers of eumelanin producing melanocytes and, accordingly, darker skin (as displayed by the indigenous people of Africa, today). As some of these original peoples migrated and settled in areas of Asia and Europe, the selective pressure for eumelanin production decreased in climates where radiation from the sun was less intense. Thus variations in genes involved in melanin production began to appear in the population, resulting in lighter hair and skin in humans residing at northern latitudes. Studies have been carried out to determine whether these changes were due to genetic drift or positive selection, perhaps driven by requirement for vitamin D. Of the two common gene variants known to be associated with pale human skin, Mc1r[17] does not appear to have undergone positive selection, while SLC24A5[18] has.
As with peoples who migrated northward, those with light skin who migrate southward acclimatize to the much stronger solar radiation. Most people's skin darkens when exposed to UV light, giving them more protection when it is needed. This is the physiological purpose of sun tanning. Dark-skinned people, who produce more skin-protecting eumelanin, have a greater protection against sunburn and the development of melanoma, a potentially deadly form of skin cancer, as well as other health problems related to exposure to strong solar radiation, including the photodegradation of certain vitamins such as riboflavins, carotenoids, tocopherol, and folate.
Melanin in the eyes helps protect them from ultraviolet and high-frequency visible light; people with blue eyes are more at risk for sun-related eye problems. Further, the ocular lens yellows with age, providing added protection. However, the lens also becomes more rigid with age, losing most of its accommodation — the ability to change shape to focus from far to near — a detriment due probably to protein crosslinking caused by UV exposure.
Recent research by J.D. Simon et al. (Pigment Cell Research, 2004, 17: 262-269) suggests that melanin may serve a protective role other than photoprotection. Melanin is able to effectively ligate metal ions through its carboxylate and phenolic hydroxyl groups, in many cases much more efficiently than the powerful chelating ligand ethylenediaminetetraacetate (EDTA). It may thus serve to sequester potentially toxic metal ions, protecting the rest of the cell. This hypothesis is supported by the fact that the loss of neuromelanin observed in Parkinson's disease is accompanied by an increase in iron levels in the brain.
# Physical properties and technological applications
Melanins are "rigid-backbone" conductive polymers composed of polyacetylene, polypyrrole, and polyaniline "Blacks" and their mixed copolymers. The simplist melanin is polyacetylene, from which all others derive. Some fungal melanins are pure polyacetylene.
In 1963, DE Weiss and coworkers reported [3] high electrical conductivity in a melanin, iodine-doped and oxidized polypyrrole "Black". They achieved the quite high conductivity of 1 Ohm/cm. A decade later, John McGinness, and coworkers reported a high conductivity "ON" state in a voltage-controlled solid-state threshold switch made with DOPA melanin [4]. Further, this material emitted a flash of light—electroluminescence—when it switched. Melanin also shows negative resistance, a classic property of electronically-active conductive polymers. Likewise, melanin is the best sound-absorbing material known[19] due to strong electron-phonon coupling. This may be related to melanin's presence in the inner ear.
These early discoveries were "lost" until the recent emergence of such melanins in device applications, particularly electroluminescent displays. In 2000, the Nobel Prize in Chemistry was awarded to three scientists for their subsequent 1977 (re)discovery and development of such conductive organic polymers. In an essential reprise of Weiss et al's work, these polymers were oxidized, iodine-doped "polyacetylene black" melanins. There is no evidence the Nobel committee was aware of Weiss et als [5] almost identical prior report of passive high conductivity in iodinated polypyrrole black or of switching and high electrical conductivity in DOPA melanin and related organic semiconductors. The melanin organic electronic device is now in the Smithsonian Institution's National Museum of American History's "Smithsonian Chips" collection of historic solid-state electronic devices.
Melanin influences neural activity and mediates the conduction of radiation, light, heat and kinetic energy. As such, it is the subject of intense interest in biotech research and development, most notably in organic electronics (sometimes called "plastic electronics") and nanotechnology, where dopants are used to dramatically boost melanin conductivity. Pyrrole black and acetylene black are the most commonly studied organic semiconductors.
Although synthetic melanin (commonly referred to as BSM, or "black synthetic matter") is made up of 3-6 oligomeric units linked together—the so-called "protomolecule"—there is no evidence that naturally occurring biopolymer (BCM, for "black cell matter") mimics this structure. However, since there is no reason to believe that natural melanin does not belong to the category of the polyarenes and polycationic polyenes, like pyrrol black and acetylene black, it is necessary to review all the chemical and biological analytic data gathered to date in the study of natural melanins (eumelanins, pheomelanins, allomelanins)." [6]
Evidence exists in support of a highly cross-linked heteropolymer bound covalently to matrix scaffolding melanoproteins (Eur. J. Biochem. 1995; 232: 159-164 "Interaction of melanosomal proteins with melanin). It has been proposed that the ability of melanin to act as an antioxidant is directly proportional to its degree of polymerization or molecular weight (Ophthalmic research, 2005, 37: 136-141 "Melanin aggregation and polymerization: possible implications in age related macular degeneration"). Suboptimal conditions for the effective polymerization of melanin monomers may lead to formation of lower-molecular-weight, pro-oxidant melanin that is has been implicated in the causation and progression of macular degeneration and melanoma. (Clinical Cancer Res. 2004; 10: 2581-2583 "Etiologic pathogenesis of melanoma: a unifying hypothesis for the missing attributable risk"). Signaling pathways that upregulate melanization in the retinal pigment epithelium (RPE) also may be implicated in the downregulation of rod outer segment phagocytosis by the RPE. This phenomenon has been attributed in part to foveal sparing in macular degeneration. (Mol. Vis. 2005; 11: 482-490 "Melanization and phagocytosis: implications for age-related macular degeneration).
# Melanin-based bias in human societies
When skin pigmentation as a characteristic of race is linked to social status or other human attributes, this phenomenon is known as racialism. Many people and societies overlay racialism with racist perceptions and systems which arbitrarily assign to groups of people a status of inherent superiority or inferiority, privilege or disadvantage based on skin color or racial classification. Apartheid-era South Africa is an example of a white supremacist society based on a system of stratification of power and privilege by skin color, as well as racial admixture. Similar examples can be found in India's caste system; Brazil's highly socially color-stratified society; and, in the U.S., segregation and institutional racism on the part of white-controlled institutions, and internal "color consciousness" on the part of members of some ethnic minorities. Because of the pervasive influence of white supremacist values worldwide, prejudice against people with more highly pigmented skin is the most pervasive form of color bias. Conversely, black supremacy is a far less pervasive phenomenon. Many other societies remain informally divided on the basis of skin color and, often, related ethnicity. (See also colonialism, Nazism and institutional racism.)
Illogical presumptions about people with regard to hair color are far less common than skin-color bias, have far fewer and less serious real-world implications, and are more often applied to women than to men. Common stereotypes in the West are dumb blondes, hot-tempered redheads and vixen brunettes. | https://www.wikidoc.org/index.php/Eumelanin | |
b01a5828860335f2094f7d75009dd828cd58f4e9 | wikidoc | Exudate | Exudate
# Overview
An exudate is any fluid that filters from the circulatory system into lesions or areas of inflammation. Its composition varies but generally includes water and the dissolved solutes of the blood, some or all plasma proteins, white blood cells, platelets and (in the case of local vascular damage) red blood cells.
Pus is an example of exudate found in infected wounds that also includes bacteria and high concentrations of white blood cells. Clear blister fluid is an example of an exudate that contains water (and solutes) together with some plasma proteins, but not many blood cells.
Serous exudate is usually seen in mild inflammation, with little protein content. Its consistency resembles that of serum, and can usually be seen in certain disease states like tuberculosis.
Purulent or suppurative exudate consists of plasma with both active and dead neutrophils, fibrinogen, and necrotic parenchymal cells. This kind of exudate is consistent with more severe infections, and is commonly referred to as pus.
Fibrinous exudate is composed mainly of fibrinogen and fibrin. It is characteristic of rheumatic carditis, but is seen in all severe injuries such as strep throat and bacterial pneumonia. Fibrinous inflammation is often difficult to resolve due to the fact that blood vessels grow into the exudate and fill the space that was occupied by fibrin. Often, large amounts of antiboiotics are necessary for resolution.
Hemorrhagic exudate is seen in injury that causes rupture of blood vessels.
Pleural exudate has a specific gravity greater than 1.020. Certain conditions produce exudative pleural effusions such as infections, pulmonary infarctions, rheumatoid arthritis, lupus erythematosus, and certain malignancies.
Catarrhal exudate is seen in the nose and throat and is characterized by a high content of mucus.
There is an important distinction between transudates and exudates. Transudates are caused by disturbances of hydrostatic or colloid osmotic pressure, not by inflammation. Medical distinction between transudates and exudates is through the measurement of the specific gravity of extracted fluid. Specific gravity is used to measure the protein content of the fluid. The higher the specific gravity, the greater the likelihood of capillary permeability changes in relation to body cavities. For example, the specific gravity of the transudate is usually less than 1.012. | Exudate
# Overview
An exudate is any fluid that filters from the circulatory system into lesions or areas of inflammation. Its composition varies but generally includes water and the dissolved solutes of the blood, some or all plasma proteins, white blood cells, platelets and (in the case of local vascular damage) red blood cells.
Pus is an example of exudate found in infected wounds that also includes bacteria and high concentrations of white blood cells. Clear blister fluid is an example of an exudate that contains water (and solutes) together with some plasma proteins, but not many blood cells.
Serous exudate is usually seen in mild inflammation, with little protein content. Its consistency resembles that of serum, and can usually be seen in certain disease states like tuberculosis.
Purulent or suppurative exudate consists of plasma with both active and dead neutrophils, fibrinogen, and necrotic parenchymal cells. This kind of exudate is consistent with more severe infections, and is commonly referred to as pus.
Fibrinous exudate is composed mainly of fibrinogen and fibrin. It is characteristic of rheumatic carditis, but is seen in all severe injuries such as strep throat and bacterial pneumonia. Fibrinous inflammation is often difficult to resolve due to the fact that blood vessels grow into the exudate and fill the space that was occupied by fibrin. Often, large amounts of antiboiotics are necessary for resolution.
Hemorrhagic exudate is seen in injury that causes rupture of blood vessels.
Pleural exudate has a specific gravity greater than 1.020. Certain conditions produce exudative pleural effusions such as infections, pulmonary infarctions, rheumatoid arthritis, lupus erythematosus, and certain malignancies.
Catarrhal exudate is seen in the nose and throat and is characterized by a high content of mucus.
There is an important distinction between transudates and exudates. Transudates are caused by disturbances of hydrostatic or colloid osmotic pressure, not by inflammation. Medical distinction between transudates and exudates is through the measurement of the specific gravity of extracted fluid. Specific gravity is used to measure the protein content of the fluid. The higher the specific gravity, the greater the likelihood of capillary permeability changes in relation to body cavities. For example, the specific gravity of the transudate is usually less than 1.012. | https://www.wikidoc.org/index.php/Exudate | |
7908f83c8ecc18cceadb2cebd72c0e5d9d80cc19 | wikidoc | Eyelash | Eyelash
# Overview
An eyelash or simply lash is one of the hairs that grow at the edge of the eyelid. Eyelashes protect the eye from debris and perform some of the same function as whiskers do on a cat or a mouse in the sense that they are sensitive to being touched, thus providing a warning that an object (such as an insect or dust mite) is near the eye (which is then closed reflexively).
# Human eyelashes
The eyelashes of the embryo develop between the 7th and 8th week. Eyelashes will grow back if they fall out or get pulled out. Eyelashes take about four to eight weeks to grow back. Their color may differ from that of the hair, although they tend to be dark on someone with dark hair and lighter on someone with light hair.
The follicles of eyelashes are associated with a number of glands known as the glands of Zeiss and the glands of Moll.
# Cosmetics
Long eyelashes are considered a sign of femininity in most if not all cultures. Accordingly, some women seek to enhance their eyelash length artificially to appear more feminine and sexually desirable. See also eyelash extensions.
Kohl has been worn as far back as the Bronze Age to protect and enhance lashes.
Complete eye makeup includes mascara, eyeliner and eye shadow to emphasize the eyes. The twentieth century saw the beginning of convincing-looking false eyelashes, popular in the 1960s.
# Health
There are a number of diseases or disorders involving the eyelashes:
- Madarosis is the loss of eyelashes
- Blepharitis is the irritation of the lid margin (where eyelashes join the eyelid). Eyelids are red and itching. The skin often becomes flaky. The eyelashes may fall.
- Distichiasis is the abnormal growth of lashes from certain areas of the eyelid.
- Trichiasis is ingrown eyelashes
- Eyelashes may become infested with crab louse parasites
- An external hordeolum, or stye, is a purulent inflammation of infected eyelash follicles and surrounding sebaceous (Zeis) and apocrine (Moll) glands of the lid margin.
- Trichotillomania is a disorder that urges the sufferer to pull out scalp hair, eyelashes, etc.
- Demodex folliculorum (or the demodicid), is a small mite that lives, harmlessly, in eyelash and other hair follicles and around 98% of people have these mites living on them. Occasionally they can cause blepharitis.
Eyelash and eyebrow transplant surgeries may help to reconstruct or thicken lashes or eyebrow hair.
# Animals
Lashes, being hair, are found in mammals. Camels' lashes are remarkably long and thick, and giraffe's eyelashes are considered by some to be more beautiful than a human's. Horses, cows, and also ostriches, (vestigial feathers without barbs) feature eyelashes as well.
Inherited eyelash problems are common in some breeds of dogs.
Eyelash vipers show a set of modified scales over the eyes which look much like eyelashes.
Hornbills have prominent feather eyelashes, an uncommon feature in birds.
# Mythology and trivia
- Hera was said to have cow's eyes (Greek boôpis).
- In Thai art, Buddha is said to have "eyelashes like a cow's".
- When Ymir (or Aurgelmir) was slaughtered by his grandson Odin, his eyebrows became Midgard, the world of men. The gods set up Ymir's eyelashes to keep the giants at the edges of the earth disk.
- Porcelain dolls have moving eyelids with detailed eyelashes.
- Betty Boop is depicted with great eyelashes and eyelid flutter ability.
- Snoopy’s sister, Belle, looks like him but has long eyelashes.
- Some believe that finding an eyelash is very good luck
- Some believe that the same collection of factors that brought about long eyelashes in human females also occurred in other species and that one can tell the sex of some types of mammals (such as cats) by looking at the eyelashes and shape of the brow.
- It is said that if you happen to find that you lost an eyelash and it is in your hand, you can make a wish by just saying the wish softly and blowing the eyelash out of your hand. It will not work if you pull one. | Eyelash
# Overview
An eyelash or simply lash is one of the hairs that grow at the edge of the eyelid. Eyelashes protect the eye from debris and perform some of the same function as whiskers do on a cat or a mouse in the sense that they are sensitive to being touched, thus providing a warning that an object (such as an insect or dust mite) is near the eye (which is then closed reflexively).
# Human eyelashes
The eyelashes of the embryo develop between the 7th and 8th week. Eyelashes will grow back if they fall out or get pulled out. Eyelashes take about four to eight weeks to grow back. Their color may differ from that of the hair, although they tend to be dark on someone with dark hair and lighter on someone with light hair.
The follicles of eyelashes are associated with a number of glands known as the glands of Zeiss and the glands of Moll.
# Cosmetics
Long eyelashes are considered a sign of femininity in most if not all cultures. Accordingly, some women seek to enhance their eyelash length artificially to appear more feminine and sexually desirable. See also eyelash extensions.
Kohl has been worn as far back as the Bronze Age to protect and enhance lashes.
Complete eye makeup includes mascara, eyeliner and eye shadow to emphasize the eyes. The twentieth century saw the beginning of convincing-looking false eyelashes, popular in the 1960s.
# Health
There are a number of diseases or disorders involving the eyelashes:
- Madarosis is the loss of eyelashes
- Blepharitis is the irritation of the lid margin (where eyelashes join the eyelid). Eyelids are red and itching. The skin often becomes flaky. The eyelashes may fall.
- Distichiasis is the abnormal growth of lashes from certain areas of the eyelid.
- Trichiasis is ingrown eyelashes
- Eyelashes may become infested with crab louse parasites
- An external hordeolum, or stye, is a purulent inflammation of infected eyelash follicles and surrounding sebaceous (Zeis) and apocrine (Moll) glands of the lid margin.[1]
- Trichotillomania is a disorder that urges the sufferer to pull out scalp hair, eyelashes, etc.
- Demodex folliculorum (or the demodicid), is a small mite that lives, harmlessly, in eyelash and other hair follicles and around 98% of people have these mites living on them. Occasionally they can cause blepharitis.
Eyelash and eyebrow transplant surgeries may help to reconstruct or thicken lashes or eyebrow hair.[2]
# Animals
Lashes, being hair, are found in mammals. Camels' lashes are remarkably long and thick, and giraffe's eyelashes are considered by some to be more beautiful than a human's. Horses, cows, and also ostriches, (vestigial feathers without barbs) feature eyelashes as well.
Inherited eyelash problems are common in some breeds of dogs.
Eyelash vipers show a set of modified scales over the eyes which look much like eyelashes.
Hornbills have prominent feather eyelashes, an uncommon feature in birds.
# Mythology and trivia
- Hera was said to have cow's eyes (Greek boôpis).
- In Thai art, Buddha is said to have "eyelashes like a cow's".
- When Ymir (or Aurgelmir) was slaughtered by his grandson Odin, his eyebrows became Midgard, the world of men. The gods set up Ymir's eyelashes to keep the giants at the edges of the earth disk. [1] [2]
- Porcelain dolls have moving eyelids with detailed eyelashes.
- Betty Boop is depicted with great eyelashes and eyelid flutter ability.
- Snoopy’s sister, Belle, looks like him but has long eyelashes.
- Some believe that finding an eyelash is very good luck
- Some believe that the same collection of factors that brought about long eyelashes in human females also occurred in other species and that one can tell the sex of some types of mammals (such as cats) by looking at the eyelashes and shape of the brow.
- It is said that if you happen to find that you lost an eyelash and it is in your hand, you can make a wish by just saying the wish softly and blowing the eyelash out of your hand. It will not work if you pull one. | https://www.wikidoc.org/index.php/Eyelash | |
a52bded9d6b62fc0d0ba4a479204ba4cc872eb5e | wikidoc | Vytorin | Vytorin
For patient information about Ezetimibe/Simvastatin, click here.
Synonyms / Brand Names: VYTORIN®
# Overview
Ezetimibe/simvastatin /ɛˈzɛtmɪb ˌsɪmvəˈstætn/ is a drug combination used for the treatment of dyslipidemia. It is a combination of ezetimibe (known as Zetia in the United States and Ezetrol elsewhere) and the statin drug simvastatin (known as Zocor in the U.S.). The combination preparation is marketed by Merck & Co. under the trade names Vytorin and Inegy.
Ezetimibe reduces blood cholesterol by acting at the brush border of the small intestine and inhibiting the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver.
Simvastatin is an HMG-CoA reductase inhibitor or statin. It works by blocking an enzyme that is necessary for the body to make cholesterol.
Even though ezetimibe decreases cholesterol levels, as of 2009 it has not been found to lead to improvement in real world outcomes. The combination of simvastatin and ezetimibe has not been found to be any better than simvastatin alone. A panel of experts thus concluded in 2008 that it should "only be used as a last resort".
# Category
Category:Schering-Plough;Merck;Hypolipidemic agents;Cardiovascular Drugs
# FDA Package Insert
Indications and Usage
# Mechanism of Action
## VYTORIN
Plasma cholesterol is derived from intestinal absorption and endogenous synthesis. VYTORIN contains ezetimibe and simvastatin, two lipid-lowering compounds with complementary mechanisms of action. VYTORIN reduces elevated total-C, LDL-C, Apo B, TG, and non-HDL-C, and increases HDL-C through dual inhibition of cholesterol absorption and synthesis.
## Ezetimibe
Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine. The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols. In a 2-week clinical study in 18 hypercholesterolemic patients, ezetimibe inhibited intestinal cholesterol absorption by 54%, compared with placebo. Ezetimibe had no clinically meaningful effect on the plasma concentrations of the fat-soluble vitamins A, D, and E and did not impair adrenocortical steroid hormone production.
Ezetimibe localizes at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood; this distinct mechanism is complementary to that of statins.
## Simvastatin
Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In addition, simvastatin reduces very-low-density lipoproteins (VLDL) and TG and increases HDL-C.
# Interaction with Alcohol
VYTORIN should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease. | Vytorin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]
For patient information about Ezetimibe/Simvastatin, click here.
Synonyms / Brand Names: VYTORIN®
# Overview
Ezetimibe/simvastatin /ɛˈzɛt[invalid input: 'ɨ']mɪb ˌsɪmvəˈstæt[invalid input: 'ɨ']n/ is a drug combination used for the treatment of dyslipidemia. It is a combination of ezetimibe (known as Zetia in the United States and Ezetrol elsewhere) and the statin drug simvastatin (known as Zocor in the U.S.). The combination preparation is marketed by Merck & Co. under the trade names Vytorin and Inegy.
Ezetimibe reduces blood cholesterol by acting at the brush border of the small intestine and inhibiting the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver.
Simvastatin is an HMG-CoA reductase inhibitor or statin. It works by blocking an enzyme that is necessary for the body to make cholesterol.
Even though ezetimibe decreases cholesterol levels, as of 2009 it has not been found to lead to improvement in real world outcomes.[1] The combination of simvastatin and ezetimibe has not been found to be any better than simvastatin alone. A panel of experts thus concluded in 2008 that it should "only be used as a last resort".[2]
# Category
Category:Schering-Plough;Merck;Hypolipidemic agents;Cardiovascular Drugs
# FDA Package Insert
Indications and Usage
# Mechanism of Action
## VYTORIN
Plasma cholesterol is derived from intestinal absorption and endogenous synthesis. VYTORIN contains ezetimibe and simvastatin, two lipid-lowering compounds with complementary mechanisms of action. VYTORIN reduces elevated total-C, LDL-C, Apo B, TG, and non-HDL-C, and increases HDL-C through dual inhibition of cholesterol absorption and synthesis.
## Ezetimibe
Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine. The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols. In a 2-week clinical study in 18 hypercholesterolemic patients, ezetimibe inhibited intestinal cholesterol absorption by 54%, compared with placebo. Ezetimibe had no clinically meaningful effect on the plasma concentrations of the fat-soluble vitamins A, D, and E and did not impair adrenocortical steroid hormone production.
Ezetimibe localizes at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood; this distinct mechanism is complementary to that of statins[see Clinical Studies (14)].
## Simvastatin
Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In addition, simvastatin reduces very-low-density lipoproteins (VLDL) and TG and increases HDL-C.
# Interaction with Alcohol
VYTORIN should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease. | https://www.wikidoc.org/index.php/Ezetimibe/Simvastatin | |
f436c2d753edab08f9f26ba20904258456701949 | wikidoc | f-block | f-block
The f-block of the periodic table of the elements consists of those elements (sometimes referred to as the inner transition elements) for which, in the atomic ground state, the highest-energy electrons occupy f-orbitals.
Unlike the other blocks, the conventional divisions of the f-block follow periods of similar atomic number rather than groups of similar electron configuration. Thus, the f-block is divided into the lanthanoid series and the actinoid series.
The name 'inner transition' is derived by analogy with the transition metals.
Like the s-block, the elements of the f-block are highly reactive metals. They catch fire in air very easily, and react with water to liberate hydrogen. Physically they are denser and have higher melting and boiling points than the alkaline earth metals, but their reactivity makes them of very limited use structurally. They are used together to make cigarette lighter flints because they catch fire in air so easily. Most of them are extracted by electrolysis of molten chlorides: the metals are much too reactive to be extractable from aqueous solutions.
The compounds of most f-block elements are ionic salts with M3+ ions, often hydrated in aqueous solutions. Cerium also forms a small series of strongly oxidising compounds with the +4 oxidation state, including ceric oxide (CeO2). The lighter actinides (protactinium to americium) have f-electrons that can participate in bonding and form compounds in a variety of oxidation states from +2 to +6. Owing to the pulling of the inner f-electrons towards the nucleus, the heavier actinides (curium to lawrencium) tend not to use their inner f-electrons and resemble the lanthanides in forming salts with M3+ ions.
Interactive f-orbital models can be found at this site: | f-block
The f-block of the periodic table of the elements consists of those elements (sometimes referred to as the inner transition elements) for which, in the atomic ground state, the highest-energy electrons occupy f-orbitals.
Unlike the other blocks, the conventional divisions of the f-block follow periods of similar atomic number rather than groups of similar electron configuration. Thus, the f-block is divided into the lanthanoid series and the actinoid series. [1] [2]
The name 'inner transition' is derived by analogy with the transition metals.
Like the s-block, the elements of the f-block are highly reactive metals. They catch fire in air very easily, and react with water to liberate hydrogen. Physically they are denser and have higher melting and boiling points than the alkaline earth metals, but their reactivity makes them of very limited use structurally. They are used together to make cigarette lighter flints because they catch fire in air so easily. Most of them are extracted by electrolysis of molten chlorides: the metals are much too reactive to be extractable from aqueous solutions.
The compounds of most f-block elements are ionic salts with M3+ ions, often hydrated in aqueous solutions. Cerium also forms a small series of strongly oxidising compounds with the +4 oxidation state, including ceric oxide (CeO2). The lighter actinides (protactinium to americium) have f-electrons that can participate in bonding and form compounds in a variety of oxidation states from +2 to +6. Owing to the pulling of the inner f-electrons towards the nucleus, the heavier actinides (curium to lawrencium) tend not to use their inner f-electrons and resemble the lanthanides in forming salts with M3+ ions.
Interactive f-orbital models can be found at this site:[1] | https://www.wikidoc.org/index.php/F-block | |
5de08c32134202c148511218fea7e72ed9a4fc03 | wikidoc | FAM107B | FAM107B
FAM107B is a gene found in humans. It is located on the minus strand of chromosome 10, p13, which is on the short arm of the chromosome. It has other alias names, such as C10orf45, FLJ45505, MGC11034 and MGC90261. The gene contains a conserved domain, DUF1151, which is a family that consists of several eukaryotic proteins of unknown function. FAM107B is expressed in most tissues in the human body without there being a high frequency in any one tissue. It is found in all stages of human development.
# Gene
The mRNA for FAM107B is 3785 base pairs long and contains five exons. The protein for FAM107B is known as LOC83641. It is 306 amino acids long. According to AceView, there are 27 spliced variants with 2 unspliced variants and 27 mRNAs of FAM107B. Of these variants and mRNAs, only 23 spliced and unspliced mRNAs are known to encode proteins of quality. Additionally, there appear to be 17 different isoforms. FAM107B is not a signal peptide, but is thought to be a protein that is exported to the mitochondria. It has the following genes located in its gene neighborhood: FRMD4A (FERM domain containing 4A); LOC100289125 (hypothetical protein LOC100289125); RPSAP7 (ribosomal protein SA pseudogene 7 in Homo sapiens); CDNF (cerebral dopamine neurotrophic factor; HSPA14.
FAM107B has one paralog, FAM107A, and many orthologs in organisms including primates, dogs, cows, mice, and chickens. With these orthologs, there is a high degree of conservation.
# Structure
Two structures have a high similarity to that of FAM107B: that of a human septin trimer in Homo sapiens and that of the 3rd HMG-box of mouse UBF1. The septin trimer is that of a Ras-like GTPase superfamily whose members are known to regulate cytoskeletal reorganization, gene expression, vesicle trafficking, nucleocytoplasmic transport, and microtubule organization. The 3rd HMG-box of Mouse Ubf is part of the HMG-box superfamily whose members bind to DNA to bend or distort it where it can cause looping of linear DNA, create four-way DNA junctions, and DNA bulges. Members of this family also include mitochondrial transcription factors that bind at four-way DNA junctions.
# Interacting proteins
Proteins exist that interact with the FAM107B protein:
- autophagy proteins that are involved in the transport from the cytoplasm to the vacuole, and specifically Cvt vesicle formation;
- the probable protein kinase, which is a heat shock-like protein as well as an antigen;
- the kinesin-related protein which is a biliary glycoprotein isoantigen;
- the hypothetical protein HP0231, which is a somatostatin receptor, as well as the ISWI complex protein 2, which is a mitochondrial reverse transcriptose-like protein;
- the CG7077-PA open reading frame protein, which is known for the Alu repetitive sequence.
# Model organisms
Model organisms have been used in the study of FAM107B function. A conditional knockout mouse line, called Fam107btm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty six tests were carried out on mutant mice and two significant abnormalities were observed: homozygous animals had abnormal brainstem auditory evoked potential and increased trabecular bone thickness. | FAM107B
FAM107B is a gene found in humans. It is located on the minus strand of chromosome 10, p13, which is on the short arm of the chromosome. It has other alias names, such as C10orf45, FLJ45505, MGC11034 and MGC90261. The gene contains a conserved domain, DUF1151, which is a family that consists of several eukaryotic proteins of unknown function. FAM107B is expressed in most tissues in the human body without there being a high frequency in any one tissue. It is found in all stages of human development.
# Gene
The mRNA for FAM107B is 3785 base pairs long and contains five exons. The protein for FAM107B is known as LOC83641. It is 306 amino acids long. According to AceView, there are 27 spliced variants with 2 unspliced variants and 27 mRNAs of FAM107B. Of these variants and mRNAs, only 23 spliced and unspliced mRNAs are known to encode proteins of quality. Additionally, there appear to be 17 different isoforms. FAM107B is not a signal peptide, but is thought to be a protein that is exported to the mitochondria. It has the following genes located in its gene neighborhood: FRMD4A (FERM domain containing 4A); LOC100289125 (hypothetical protein LOC100289125); RPSAP7 (ribosomal protein SA pseudogene 7 in Homo sapiens); CDNF (cerebral dopamine neurotrophic factor; HSPA14.
FAM107B has one paralog, FAM107A, and many orthologs in organisms including primates, dogs, cows, mice, and chickens. With these orthologs, there is a high degree of conservation.
# Structure
Two structures have a high similarity to that of FAM107B: that of a human septin trimer in Homo sapiens and that of the 3rd HMG-box of mouse UBF1. The septin trimer is that of a Ras-like GTPase superfamily whose members are known to regulate cytoskeletal reorganization, gene expression, vesicle trafficking, nucleocytoplasmic transport, and microtubule organization. The 3rd HMG-box of Mouse Ubf is part of the HMG-box superfamily whose members bind to DNA to bend or distort it where it can cause looping of linear DNA, create four-way DNA junctions, and DNA bulges. Members of this family also include mitochondrial transcription factors that bind at four-way DNA junctions.
# Interacting proteins
Proteins exist that interact with the FAM107B protein:
- autophagy proteins that are involved in the transport from the cytoplasm to the vacuole, and specifically Cvt vesicle[clarification needed] formation;
- the probable protein kinase, which is a heat shock-like protein as well as an antigen;
- the kinesin-related protein which is a biliary glycoprotein isoantigen;
- the hypothetical protein HP0231, which is a somatostatin receptor, as well as the ISWI complex protein 2, which is a mitochondrial reverse transcriptose-like protein;
- the CG7077-PA open reading frame protein, which is known for the Alu repetitive sequence.
# Model organisms
Model organisms have been used in the study of FAM107B function. A conditional knockout mouse line, called Fam107btm1a(KOMP)Wtsi[5][6] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[7][8][9]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[3][10] Twenty six tests were carried out on mutant mice and two significant abnormalities were observed: homozygous animals had abnormal brainstem auditory evoked potential and increased trabecular bone thickness.[3] | https://www.wikidoc.org/index.php/FAM107B | |
2bd77928e2dc4470dfa0a33b1d5f646f360405d0 | wikidoc | FAM134C | FAM134C
Protein FAM134C is a protein that in humans is encoded by the FAM134C (family with sequence similarity 134, member C) gene.
# Model organisms
Model organisms have been used in the study of FAM134C function. A conditional knockout mouse line, called Fam134ctm2a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on mutant mice and four significant abnormalities were observed. Homozygous animals had an abnormal xyphoid process and eye morphology. Females had increased indirect calorimetry parameters while males had an increased susceptibility to bacterial infection. | FAM134C
Protein FAM134C is a protein that in humans is encoded by the FAM134C (family with sequence similarity 134, member C) gene.[1]
# Model organisms
Model organisms have been used in the study of FAM134C function. A conditional knockout mouse line, called Fam134ctm2a(EUCOMM)Wtsi[7][8] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[9][10][11]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty four tests were carried out on mutant mice and four significant abnormalities were observed.[5] Homozygous animals had an abnormal xyphoid process and eye morphology.[12] Females had increased indirect calorimetry parameters while males had an increased susceptibility to bacterial infection.[5] | https://www.wikidoc.org/index.php/FAM134C | |
50c09b2bedaa378d81553121914cd880a29a3c3c | wikidoc | FAM135B | FAM135B
FAM135B is a human gene coding for a protein of unknown function. It is well conserved in primates, rodents, zebra fish. It has one paralog, FAM135A.
# Gene
FAM135B is located on the long arm of Chromosome 8 in humans on the anti-sense located at 24.23. The following genes are near FAM135B on the chromosome:
- COL22A1: Collagen producing gene that is a cell adhesion ligand for skin epithelial cells and fibroblast
- FLJ45972: Gene function is unknown
- KCNK9: Gene that encodes for a two pore potassium channel
# Expression
FAM135B is expressed in the brain, ear, eye, pancreas and testis. Within the brain, expression is apparent within the motor nucleus of trigeminal In addition, it is mainly expressed in normal health states, although it has shown moderate expression in glioma, non-neoplasima as well as expression in germ cell tumors.
File:Visual Representation of expression in mouse brain.png
# Interactions
FAM135B has shown to interact with KAT5, a gene that encodes for a histone acetyltransferase through yeast two-hybrid experimentation.
# Protein
The protein encoded on FAM135 is 1406 amino acids long. The protein contains a region called DUF676, believed to be a putative serine esterase as well as two protein regions called DUF3657.
# Clinical significance
FAM135B has shown to be expressed in individuals with extrapulmonary tuberculosis. | FAM135B
FAM135B is a human gene coding for a protein of unknown function.[1] It is well conserved in primates, rodents, zebra fish. It has one paralog, FAM135A.
# Gene
FAM135B is located on the long arm of Chromosome 8 in humans on the anti-sense located at 24.23.[1] The following genes are near FAM135B on the chromosome:
- COL22A1: Collagen producing gene that is a cell adhesion ligand for skin epithelial cells and fibroblast
- FLJ45972: Gene function is unknown
- KCNK9: Gene that encodes for a two pore potassium channel
# Expression
FAM135B is expressed in the brain, ear, eye, pancreas and testis.[2] Within the brain, expression is apparent within the motor nucleus of trigeminal[3] In addition, it is mainly expressed in normal health states, although it has shown moderate expression in glioma, non-neoplasima as well as expression in germ cell tumors.[2]
File:Visual Representation of expression in mouse brain.png
# Interactions
FAM135B has shown to interact with KAT5, a gene that encodes for a histone acetyltransferase[4] through yeast two-hybrid experimentation.
# Protein
The protein encoded on FAM135 is 1406 amino acids long. The protein contains a region called DUF676, believed to be a putative serine esterase as well as two protein regions called DUF3657.[1]
# Clinical significance
FAM135B has shown to be expressed in individuals with extrapulmonary tuberculosis.[5] | https://www.wikidoc.org/index.php/FAM135B | |
0288ec1c25fe536fdcfe101c016109c99b5e233b | wikidoc | FAM149A | FAM149A
Family with sequence similarity 149, member A is a protein that in humans is encoded by the FAM149A gene (also known as MSTP119, MST119 and DKFZP564J102). It is well conserved in primates, dog, cow, mouse, rat, and chicken. It has one paralog, FAM149B.
# Overview
FAM149A is found in normal cardiac tissue of Homo sapiens and has been submitted to the Molecular Medicine Center for Cardiovascular Disease in 1999. Thus, this indicates it must play an important role in normal heart regulation. However, no variation report or information of clinical significance has been found for this gene, according to NCBI. According to the Basic Local Alignment Search Tool (BLAST), FAM149A is similar to cDNA FLJ32604 (98% query cover), which is found in stomach tissue and has no known function. FAM149A is also similar to cDNA FLJ58677 (86% query cover), which is found in fetal kidney tissue with no known function.
Information acquired from:
# Gene
FAM149A consists of 2721 base pairs and 482 amino acids and is located on chromosome 4q35.1. It runs on the positive strand of chromosome 4. Other genes are also found nearby on the same chromosome, including TLR3, CYP4V2, FLJ38576, ORAOV1P1, and SORBS2.
The location of FAM149A on chromosome 4 at 4q35.1 in Homo sapiens
# Homology/evolution
## Paralogs and orthologs
FAM149A possess one major paralog, FAM149B. Not much is currently known about FAM149B besides its membership in the overall FAM149 family of genes.
Orthologs of FAM149A include BRTD and its four isoforms, ECCHC11 and ALMS1. These genes are all found in humans and have conserved areas with FAM149A.
## Conserved domain
FAM149A has a conserved domain of unknown function (DUF) 3719. The DUF 3719 has very little information. It is only found in eukaryotic organisms and is made of 70 amino acids. There is a conserved HLR sequence motif found in DUF 3719. Below is an image showing the DUF3719 on FAM149A.
From the Sanger Institute, the following image shows the species in which this family exists in. The purple color indicates that DUF3719 is only existent in eukaryotic organisms. Colors, such as green, would indicate that DUF3719 exists in bacteria. When this diagram is used interactively on the website, it states that 23 species in Eukaryota have the domain.
## Phylogeny
FAM149A diverged from amphibians around 400 million years ago, birds 300 million years ago and mammals, not including primates, 94 million years ago. Divergence from primates last occurred around 5 million years ago.
# Protein
## Primary sequence
As previously stated, FAM149A is made up of 482 amino acids. The amino acids which play a part in the translation of the FAM149A gene into the FAM149A protein are shown below, along with matching base pairs. The protein is located between bp 534 and bp 1982.
## Post-translational modifications
There are some programs used to determine post-translational modifications in FAM149A. The tests and results for each are listed below.
NetPhos: This will provide predicted phosphorylation sites within your protein, occurring on serines, tyrosines, and threonines. Scores are provided that indicate the quality of the predicted site. A “good” score is closer to 1.0, while a low score is closer to zero.
Results:
Phosphorylation sites predicted: Ser: 20 Thr: 16 Tyr: 2
All of these predicted sites had scores above 0.514, most between 0.8-0.9.
Image generated:
Sulfinator: This is used to predict tyrosine sulfation sites made as proteins go through secretory pathway. There were no results for FAM149A. Therefore, there aren’t any tyrosine sulfation sites.
NetAcet: Predicts N-terminal acetylation sites.
Here are the results:
According to NetAcet, there are no N-terminal acetylation sites for FAM149A.
SUMOplot/SUMOsp: Used to predict potential sumoylation sites. These may explain larger molecular weights than expected on SDS gels due to attachment of SUMO proteins.
The results can be seen below:
## Secondary structure
The secondary structure of the FAM149A protein is based on a local three-dimensional structure. The structures analyzed include the α-helix, β-strand, β-turn, and random coil. Results were obtained using GOR4 and PELE from Biology WorkBench. GOR4 is a simplified version, and PELE compares predicted structures from other programs.
# Expression
## Promoter
Here is the promoter for the FAM149A gene provided by ElDorado and the sequence extracted from the information.
The following is a FASTA formatted version of the FAM149A promoter.
## Conservation of gene structure across species
Through the NCBI website, an additional 1000 basepairs were added to the selected region on chromosome 4 containing FAM149A. Once the start and end positions were established, the positions were transferred to the ECR Browser to create an alignment across other species.
According to the results, there are 14 exons within FAM149A, which are conserved in the monkey, dog, mouse, and opossum. The chicken, frog, and fish show little to no conservation. Within the first 1000 base pairs prior to the start of the transcription, there appears to be no notable conservation across species. Only the dog contains what is considered as an Evolutionary Conserved Region (ECR).
## Expression
Based on the graphs on the right, the highest levels of expression occur in the trigeminal ganglion, superior cervical ganglion, atrioventricular node (heart), and kidney. However, at least a small amount seems to be expressed in almost all tissues in the human body. Using the same micro arrays provided by Bio GPS, expression of FAM149A was found to vary through the shedding of the endometrium during menstruation. This opens a new avenue for possible exploration of the function of the gene.
A search was performed on the Allen Brain Atlas using FAM149A. According to the levels of expression provided by the Atlas, FAM149A is not expressed in notable levels within the mouse brain. However, with visual observation of the figure, FAM149A could be found in the ventral posterior complex of the thalamus. This can be seen as the dark vertical line in the center of the sagittal brain slice in the image below. As a comparison, the expression of the protein, actin, is used to demonstrate what a mouse brain appears like with high levels of expression.
## EST profile
The data from the figure below indicates that FAM149A is highly expressed in the brain, nerves, pancreas, adrenal gland, and kidney. There is no expression in the heart. From the information in the second table, common complications involving FAM149A expression include adrenal tumors, pancreatic tumors, colorectal tumors, and ovarian tumors.
## Transcription variants
FAM149A has two transcription variants, transcript variant 1 and transcript variant 2. Both code for the same FAM149A protein. Differences include additional base pairs in the 5' untranslated area as well as the 3' untranslated region. One of two differences in the actual translated area of the protein is a G instead of an A at bp 1590 in Variant 1 and bp 1337 in Variant 2. The other difference consists of a C instead of an A at bp 2214 in TV1 and bp 1961 in TV2.
# Composition
As stated above, FAM149A is made up of 482 amino acids. The most common amino acid is serine which makes up 9.8% of the gene. The least common amino acids are tryptophan and cysteine which each make up only 1.2% of the gene. The only recurring combination of amino acids in the protein is SLAS which occurs from amino acids 234-237 and from 324-327. In addition, the Isoelectric Point of FAM149A is 9.891999
# Interacting proteins
## Transcription factor binding sites
The following is an analysis of the promoter region for FAM149A. It shows a number of transcription factor binding sites that may have strong contribution to regulating the genetic expression. The image below shows the locations of the binding sites. The binding sites were analyzed to find any possible unique functions.
There were many results, but the ones with the highest similarity and highest abundance were chosen, as they are most likely to be present on the actual gene. Matrix families of interest include the Huntington's disease gene regulatory region, nerve growth factor, nuclear respiratory factor, pleomorphic adenoma gene, zinc finger transcription factors, and an E2F-myc activator/cell cycle regulator. Many of them had interactions revolving the zinc finger complex, which suggests this may be important for FAM149A.
## Protein interactions
FAM149A has potential interactions with ZNF385D, C10orf10, PNMAL1, CPN2, C10orf72, VPS13D, and RBMS3. Based on previous research on binding sites, many were frequently involved with zinc finger proteins. According to the results from STRING, the second strongest associating protein is zinc finger protein 385D. However, it cannot be concluded these are the only interacting proteins, as it seems there is little to not research involving FAM149A interactions. The Molecular Interaction Database (MINT) was used as an additional source for protein interactions. However, FAM149A was not in the database. Based on the list of functional partners by STRING, the top 5 are also not in the MINT database. Another interaction database, I2D Protein-Protein Interaction showed possible interaction with the Protein PRKAG1, however interaction was weak.
Below is the list of proteins that potentially interact with FAM149A.
List of Potential Proteins that Interact with FAM149A.
# Clinical significance
## Disease association
While not conclusively linked, FAM149A has been found to be one of 15 candidate genes for the contribution of development of cancer and dysplastic lesions. The same paper also noted the down regulation of the gene during oral cancer, providing a possible route of study. | FAM149A
Family with sequence similarity 149, member A is a protein that in humans is encoded by the FAM149A gene (also known as MSTP119, MST119 and DKFZP564J102).[1] It is well conserved in primates, dog, cow, mouse, rat, and chicken. It has one paralog, FAM149B.
# Overview
FAM149A is found in normal cardiac tissue of Homo sapiens and has been submitted to the Molecular Medicine Center for Cardiovascular Disease in 1999. Thus, this indicates it must play an important role in normal heart regulation. However, no variation report or information of clinical significance has been found for this gene, according to NCBI. According to the Basic Local Alignment Search Tool (BLAST), FAM149A is similar to cDNA FLJ32604 (98% query cover), which is found in stomach tissue and has no known function. FAM149A is also similar to cDNA FLJ58677 (86% query cover), which is found in fetal kidney tissue with no known function.
Information acquired from:
https://www.ncbi.nlm.nih.gov/
# Gene
FAM149A consists of 2721 base pairs and 482 amino acids and is located on chromosome 4q35.1. It runs on the positive strand of chromosome 4. Other genes are also found nearby on the same chromosome, including TLR3, CYP4V2, FLJ38576, ORAOV1P1, and SORBS2.[2]
The location of FAM149A on chromosome 4 at 4q35.1 in Homo sapiens
# Homology/evolution
## Paralogs and orthologs
FAM149A possess one major paralog, FAM149B. Not much is currently known about FAM149B besides its membership in the overall FAM149 family of genes.
Orthologs of FAM149A include BRTD and its four isoforms, ECCHC11 and ALMS1. These genes are all found in humans and have conserved areas with FAM149A.
## Conserved domain
FAM149A has a conserved domain of unknown function (DUF) 3719. The DUF 3719 has very little information. It is only found in eukaryotic organisms and is made of 70 amino acids. There is a conserved HLR sequence motif found in DUF 3719. Below is an image showing the DUF3719 on FAM149A.
From the Sanger Institute, the following image shows the species in which this family exists in. The purple color indicates that DUF3719 is only existent in eukaryotic organisms. Colors, such as green, would indicate that DUF3719 exists in bacteria. When this diagram is used interactively on the website, it states that 23 species in Eukaryota have the domain.[3]
## Phylogeny
FAM149A diverged from amphibians around 400 million years ago, birds 300 million years ago and mammals, not including primates, 94 million years ago. Divergence from primates last occurred around 5 million years ago.[4]
# Protein
## Primary sequence
As previously stated, FAM149A is made up of 482 amino acids. The amino acids which play a part in the translation of the FAM149A gene into the FAM149A protein are shown below, along with matching base pairs. The protein is located between bp 534 and bp 1982.
## Post-translational modifications
There are some programs used to determine post-translational modifications in FAM149A.[5] The tests and results for each are listed below.
NetPhos: This will provide predicted phosphorylation sites within your protein, occurring on serines, tyrosines, and threonines. Scores are provided that indicate the quality of the predicted site. A “good” score is closer to 1.0, while a low score is closer to zero.
Results:
Phosphorylation sites predicted: Ser: 20 Thr: 16 Tyr: 2
All of these predicted sites had scores above 0.514, most between 0.8-0.9.
Image generated:
Sulfinator: This is used to predict tyrosine sulfation sites made as proteins go through secretory pathway. There were no results for FAM149A. Therefore, there aren’t any tyrosine sulfation sites.
NetAcet: Predicts N-terminal acetylation sites.
Here are the results:
According to NetAcet, there are no N-terminal acetylation sites for FAM149A.
SUMOplot/SUMOsp: Used to predict potential sumoylation sites. These may explain larger molecular weights than expected on SDS gels due to attachment of SUMO proteins.
The results can be seen below:
## Secondary structure
The secondary structure of the FAM149A protein is based on a local three-dimensional structure. The structures analyzed include the α-helix, β-strand, β-turn, and random coil. Results were obtained using GOR4 and PELE[6] from Biology WorkBench. GOR4 is a simplified version, and PELE compares predicted structures from other programs.
# Expression
## Promoter
Here is the promoter for the FAM149A gene provided by ElDorado[7] and the sequence extracted from the information.
The following is a FASTA formatted version of the FAM149A promoter.
## Conservation of gene structure across species
Through the NCBI website, an additional 1000 basepairs were added to the selected region on chromosome 4 containing FAM149A. Once the start and end positions were established, the positions were transferred to the ECR Browser to create an alignment across other species.
According to the results, there are 14 exons within FAM149A, which are conserved in the monkey, dog, mouse, and opossum. The chicken, frog, and fish show little to no conservation. Within the first 1000 base pairs prior to the start of the transcription, there appears to be no notable conservation across species. Only the dog contains what is considered as an Evolutionary Conserved Region (ECR).[8]
## Expression
Based on the graphs on the right, the highest levels of expression occur in the trigeminal ganglion, superior cervical ganglion, atrioventricular node (heart), and kidney. However, at least a small amount seems to be expressed in almost all tissues in the human body. Using the same micro arrays provided by Bio GPS,[9] expression of FAM149A was found to vary through the shedding of the endometrium during menstruation. This opens a new avenue for possible exploration of the function of the gene.
A search was performed on the Allen Brain Atlas using FAM149A. According to the levels of expression provided by the Atlas, FAM149A is not expressed in notable levels within the mouse brain. However, with visual observation of the figure, FAM149A could be found in the ventral posterior complex of the thalamus. This can be seen as the dark vertical line in the center of the sagittal brain slice in the image below. As a comparison, the expression of the protein, actin, is used to demonstrate what a mouse brain appears like with high levels of expression.[10]
## EST profile
The data from the figure below indicates that FAM149A is highly expressed in the brain, nerves, pancreas, adrenal gland, and kidney. There is no expression in the heart. From the information in the second table, common complications involving FAM149A expression include adrenal tumors, pancreatic tumors, colorectal tumors, and ovarian tumors.[11]
## Transcription variants
FAM149A has two transcription variants, transcript variant 1 and transcript variant 2. Both code for the same FAM149A protein. Differences include additional base pairs in the 5' untranslated area as well as the 3' untranslated region. One of two differences in the actual translated area of the protein is a G instead of an A at bp 1590 in Variant 1 and bp 1337 in Variant 2. The other difference consists of a C instead of an A at bp 2214 in TV1 and bp 1961 in TV2.
# Composition
As stated above, FAM149A is made up of 482 amino acids. The most common amino acid is serine which makes up 9.8% of the gene. The least common amino acids are tryptophan and cysteine which each make up only 1.2% of the gene. The only recurring combination of amino acids in the protein is SLAS which occurs from amino acids 234-237 and from 324-327. In addition, the Isoelectric Point of FAM149A is 9.891999[12]
# Interacting proteins
## Transcription factor binding sites
The following is an analysis of the promoter region for FAM149A. It shows a number of transcription factor binding sites that may have strong contribution to regulating the genetic expression. The image below shows the locations of the binding sites. The binding sites were analyzed to find any possible unique functions.
There were many results, but the ones with the highest similarity and highest abundance were chosen, as they are most likely to be present on the actual gene. Matrix families of interest include the Huntington's disease gene regulatory region, nerve growth factor, nuclear respiratory factor, pleomorphic adenoma gene, zinc finger transcription factors, and an E2F-myc activator/cell cycle regulator. Many of them had interactions revolving the zinc finger complex, which suggests this may be important for FAM149A.[13]
## Protein interactions
FAM149A has potential interactions with ZNF385D, C10orf10, PNMAL1, CPN2, C10orf72, VPS13D, and RBMS3.[14] Based on previous research on binding sites, many were frequently involved with zinc finger proteins. According to the results from STRING, the second strongest associating protein is zinc finger protein 385D. However, it cannot be concluded these are the only interacting proteins, as it seems there is little to not research involving FAM149A interactions. The Molecular Interaction Database (MINT) was used as an additional source for protein interactions. However, FAM149A was not in the database. Based on the list of functional partners by STRING, the top 5 are also not in the MINT database. Another interaction database, I2D Protein-Protein Interaction[15] showed possible interaction with the Protein PRKAG1, however interaction was weak.
Below is the list of proteins that potentially interact with FAM149A.
List of Potential Proteins that Interact with FAM149A.
# Clinical significance
## Disease association
While not conclusively linked, FAM149A has been found to be one of 15 candidate genes for the contribution of development of cancer and dysplastic lesions.[16] The same paper also noted the down regulation of the gene during oral cancer, providing a possible route of study. | https://www.wikidoc.org/index.php/FAM149A | |
4e885843b713d4e6970d608529df490cde3c99d9 | wikidoc | FAM162A | FAM162A
Human growth and transformation-dependent protein (HGTD-P), also called E2-induced gene 5 protein (E2IG5), is a protein that in humans is encoded by the FAM162A gene on chromosome 3. This protein promotes intrinsic apoptosis in response to hypoxia via interactions with hypoxia-inducible factor-1α (HIF-1α). As a result, it has been associated with cerebral ischemia, myocardial infarction, and various cancers.
# Structure
HGTD-P contains two transmembrane domains that are required for its localization to the mitochondria and induction of cell death.
# Function
HGTD-P localizes to the mitochondria, where it participates in regulation of apoptosis. This localization is aided by the chaperone Hsp90, which is required to stabilize the protein during the transit. HGTD-P primarily acts in response to hypoxia by interacting with HIF-1α, which then triggers apoptotic cascades that result in the release of cytochrome C, induction of mitochondrial permeability transition, and activation of caspase-9 and 3. In neuronal cells, it additionally stimulates mitochondrial release of AIFM1, which then translocates to the nucleus to effect apoptosis, which indicates that it may participate in the caspase-independent apoptotic pathway depending on cell type or organism.
# Clinical significance
Human growth and transformation-dependent protein (HGTD-P) is involved in intrinsic apoptosis. Apoptosis, an ancient Greek word used to describe the "falling off" of petals from flowers or leaves from trees, is a highly regulated, evolutionarily conserved, and energy-requiring process by which activation of specific signaling cascades ultimately leads to cell death. An apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response. It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. During apoptosis the cell decrease in size, loose contact with neighboring cells, and loose specialized surface elements such as microvilli and cell-cell junctions. A shift of fluid out of the cells causes cytoplasm condensation, which is followed by convolution of the nuclear and cellular outlines. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.
Due to its involvement in hypoxia, HGTD-P has been implicated in cerebral ischemia and myocardial infarction, as well as numerous cancers, including cervical cancer and gastric cancer. In the case of cervical cancer, HGTD-P is expressed in the early developmental stages and, thus, may prove useful as a diagnostic marker to control the spread of the cancer. Despite its proapoptotic function, HGTD-P has been observed to coordinate with HIF-1α to promote cell growth and proliferation under hypoxic conditions in cervical cancer. In the case of hypoxia-ischemia brain damage, the microRNA agomir, miR-139-5p, attenuates HGTD-P expression and brain damage, and has the therapeutic potential to treat hypoxia-ischemia brain damage.
# Interactions
HGTD-P has been shown to interact with Hsp90 and VDAC. HIF-1α is also known to bind to the hypoxia-responsive element of the HGTD-P gene promoter and induce its transcription. | FAM162A
Human growth and transformation-dependent protein (HGTD-P), also called E2-induced gene 5 protein (E2IG5), is a protein that in humans is encoded by the FAM162A gene on chromosome 3.[1][2] This protein promotes intrinsic apoptosis in response to hypoxia via interactions with hypoxia-inducible factor-1α (HIF-1α).[1][3][4][5][6][7] As a result, it has been associated with cerebral ischemia, myocardial infarction, and various cancers.[4][8][9]
# Structure
HGTD-P contains two transmembrane domains that are required for its localization to the mitochondria and induction of cell death.[4]
# Function
HGTD-P localizes to the mitochondria, where it participates in regulation of apoptosis.[1][4] This localization is aided by the chaperone Hsp90, which is required to stabilize the protein during the transit.[3][6] HGTD-P primarily acts in response to hypoxia by interacting with HIF-1α, which then triggers apoptotic cascades that result in the release of cytochrome C, induction of mitochondrial permeability transition, and activation of caspase-9 and 3.[1][3][4][6][7] In neuronal cells, it additionally stimulates mitochondrial release of AIFM1, which then translocates to the nucleus to effect apoptosis, which indicates that it may participate in the caspase-independent apoptotic pathway depending on cell type or organism.[1][5][6]
# Clinical significance
Human growth and transformation-dependent protein (HGTD-P) is involved in intrinsic apoptosis. Apoptosis, an ancient Greek word used to describe the "falling off" of petals from flowers or leaves from trees, is a highly regulated, evolutionarily conserved, and energy-requiring process by which activation of specific signaling cascades ultimately leads to cell death. An apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response.[10] It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. During apoptosis the cell decrease in size, loose contact with neighboring cells, and loose specialized surface elements such as microvilli and cell-cell junctions. A shift of fluid out of the cells causes cytoplasm condensation, which is followed by convolution of the nuclear and cellular outlines. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.
Due to its involvement in hypoxia, HGTD-P has been implicated in cerebral ischemia and myocardial infarction, as well as numerous cancers, including cervical cancer and gastric cancer.[4][8][9] In the case of cervical cancer, HGTD-P is expressed in the early developmental stages and, thus, may prove useful as a diagnostic marker to control the spread of the cancer. Despite its proapoptotic function, HGTD-P has been observed to coordinate with HIF-1α to promote cell growth and proliferation under hypoxic conditions in cervical cancer.[8] In the case of hypoxia-ischemia brain damage, the microRNA agomir, miR-139-5p, attenuates HGTD-P expression and brain damage, and has the therapeutic potential to treat hypoxia-ischemia brain damage.[7][11]
# Interactions
HGTD-P has been shown to interact with Hsp90[3] and VDAC.[4] HIF-1α is also known to bind to the hypoxia-responsive element of the HGTD-P gene promoter and induce its transcription.[5] | https://www.wikidoc.org/index.php/FAM162A | |
32f4fff5f0688fa404e42b39e104f12c763ab835 | wikidoc | FAM163A | FAM163A
FAM163A, also known as cebelin and neuroblastoma-derived secretory protein (NDSP) is a protein that in humans is encoded by the FAM163A gene. This protein has been implicated in promoting proliferation and anchorage-independent growth of neuroblastoma cancer cells. In addition, this protein has been found to be up-regulated in the lung tissue of chronic smokers. FAM163A is found on human chromosome 1q25.2; its protein product is 167 amino acids long. FAM163A contains a very highly conserved signal peptide sequence, coded for by the first ~37 amino acids in its sequence; albeit only conserved in eukaryotes, the most distant of which being the Japanese Rice Fish.
# Gene
FAM163A is approximately 2,927 base pairs long, containing five exons. While no domains of unknown function have been documented, the coding region of the gene is very short (~500 base pairs), with an exceptionally long and as-of-yet uncharacterized 3' untranslated region (UTR). FAM163A is located on the positive strand of chromosome 1, in loci126860, near three other genes: TOR1AIP1, TOR1AIP2, and TDRD5.
# mRNA
mRNA levels were tested in 45 neuroblastoma tumor samples; in 43 of these samples, elevated levels of NDSP were found, as well as in five bone marrow samples. NDSP is associated with increased risk for development of cancer metastasis in bone marrow as well as neural tissue. RNA inhibition techniques applied against NDSP decreased cellular proliferation and cancer cell colony formation. Further, this protein has been determined to act as a growth factor through an ERK-mediated pathway.
## Splice variants
Several programs can be used to generate possible splice variants of the Fam163A mRNA. The Ensembl database yields one possible splice variant, which coded for the FAM163A protein. NCBI's Aceview yields 23 possible splice variants, but no experimental evidence is associated with these.
# Protein
The human protein has a molecular weight of 17.6 kiloDaltons (kD), and an isoelectric point of 5.56. When compared across orthologs, these values are well conserved. Lastly the ExPASy program PSORTII predicts a 39.1% chance of the protein's localization in the nucleus; this being the highest probability for any location.
# Homology
The following data was generated using the NCBI BLAST program. An interesting motif in all of these sequences is the exceptional conservation of the signal peptide sequence; Vasudevan, et al.'s studies included bioinformatic analysis that compared a paralogous protein (FAM163B) in humans and the FAM163A ortholog in mice. Their results aligned with the analysis of the orthologs presented below; while many, many more orthologs exist for FAM163A in species not listed, the Japanese Rice Fish is the last orthologous species that shares the signal peptide sequence, with the next closest result having a percent identity of less than 30% and no putative domains of conservation.
## Paralogs
FAM163A has only one paralog: FAM163B, located on chromosome 9q34.2. Comparison between the two proteins reveals that the signal peptide sequence is identical; using the CLUSTALW program through SDSC's Biology Workbench, it was possible to visualize the sequences' identity.
# Tissue distribution
FAM163A is ubiquitously expressed at very low levels in most tissues of the body; expression is higher in juveniles, and as previously seen, in chronic smokers' lungs and neuroblastoma cells. | FAM163A
FAM163A, also known as cebelin and neuroblastoma-derived secretory protein (NDSP) is a protein that in humans is encoded by the FAM163A gene.[1] This protein has been implicated in promoting proliferation and anchorage-independent growth of neuroblastoma cancer cells.[2][3] In addition, this protein has been found to be up-regulated in the lung tissue of chronic smokers.[4] FAM163A is found on human chromosome 1q25.2; its protein product is 167 amino acids long. FAM163A contains a very highly conserved signal peptide sequence, coded for by the first ~37 amino acids in its sequence; albeit only conserved in eukaryotes, the most distant of which being the Japanese Rice Fish.
# Gene
FAM163A is approximately 2,927 base pairs long, containing five exons. While no domains of unknown function have been documented, the coding region of the gene is very short (~500 base pairs), with an exceptionally long and as-of-yet uncharacterized 3' untranslated region (UTR). FAM163A is located on the positive strand of chromosome 1, in loci126860, near three other genes: TOR1AIP1, TOR1AIP2, and TDRD5.[5]
# mRNA
mRNA levels were tested in 45 neuroblastoma tumor samples; in 43 of these samples, elevated levels of NDSP were found, as well as in five bone marrow samples. NDSP is associated with increased risk for development of cancer metastasis in bone marrow as well as neural tissue.[2] RNA inhibition techniques applied against NDSP decreased cellular proliferation and cancer cell colony formation. Further, this protein has been determined to act as a growth factor through an ERK-mediated pathway.[3]
## Splice variants
Several programs can be used to generate possible splice variants of the Fam163A mRNA. The Ensembl database yields one possible splice variant, which coded for the FAM163A protein.[7] NCBI's Aceview yields 23 possible splice variants, but no experimental evidence is associated with these.[8]
# Protein
The human protein has a molecular weight of 17.6 kiloDaltons (kD), and an isoelectric point of 5.56.[9] When compared across orthologs, these values are well conserved. Lastly the ExPASy program PSORTII predicts a 39.1% chance of the protein's localization in the nucleus; this being the highest probability for any location.[10]
# Homology
The following data was generated using the NCBI BLAST program.[11] An interesting motif in all of these sequences is the exceptional conservation of the signal peptide sequence; Vasudevan, et al.'s studies included bioinformatic analysis that compared a paralogous protein (FAM163B) in humans and the FAM163A ortholog in mice.[2] Their results aligned with the analysis of the orthologs presented below; while many, many more orthologs exist for FAM163A in species not listed, the Japanese Rice Fish is the last orthologous species that shares the signal peptide sequence, with the next closest result having a percent identity of less than 30% and no putative domains of conservation.
## Paralogs
FAM163A has only one paralog: FAM163B, located on chromosome 9q34.2. Comparison between the two proteins reveals that the signal peptide sequence is identical; using the CLUSTALW program through SDSC's Biology Workbench, it was possible to visualize the sequences' identity.[12]
# Tissue distribution
FAM163A is ubiquitously expressed at very low levels in most tissues of the body; expression is higher in juveniles, and as previously seen, in chronic smokers' lungs and neuroblastoma cells.[13] | https://www.wikidoc.org/index.php/FAM163A | |
a6584d81a8c9fe27af0683a6dc9a2cd5956318de | wikidoc | FAM167A | FAM167A
Family with sequence similarity 167, member A is a protein in humans that is encoded by the FAM167A gene located on chromosome 8.
FAM167A and its paralogs are protein encoding genes containing the conserved domain DUF3259, a protein of unknown function. FAM167A has many orthologs in which the domain of unknown function is highly conserved.
# Gene
## Locus
On chromosome 8, FAM167A is positioned between c8orf12 (anti-sense) and BLK (anti-sense). The exact locus of FAM167A is 8p23-22 and spans from 11,278,972 to 11,332,224, a total of 53,253 base pairs. The promoter spans from 11324145 to 11324476 on the negative strand, thereby the first basepair is actually on 11324476. There are no human isoforms found.
Gene Locus
## Aliases
Family with Sequence Similarity 167, Member A is also known as FAM167A, c8orf13, or D8S265.
# Homology
## Paralogs
FAM167A has one paralog, FAM167B also known as c1orf90. FAM167B is located at 1p35.1 on the plus strand and is composed of 163 amino acids and also contains DUF3259.
## Orthologs
FAM167A has orthologs in 82 organisms and is conserved across chimpanzees, dog, cow, mouse, chicken, rat, frogs, and zebrafish.
As shown in the table above, FAM167A is highly conserved across many orthologs of various divergence dates. The exact degree of conservation follows what is expected due to the evolutionary track of a protein.
# Protein
## Primary sequence
The gene that encodes FAM167A is 214 amino acids in length. The molecular weight in humans of the FAM167A protein is 24.2 kdal and the isoelectric point is measured to be 5.887 in Homo sapiens. Mouse and chicken orthologs were shown to have a molecular weight of ± 0.5 kdal and isoelectric points were ±0.6.
## Variants
As per the results on AceView, shown right, the FAM167A gene contains 13 introns. The gene is also "well expressed" at 1.2 times the average gene. Transcription produces 9 different mRNAs, 8 of which are alternatively spliced and 1 unspliced form. 4 of the spliced proteins, which includes 2 isoforms, are considered to be good while the remaining five are partial or not good proteins.
## Secondary structure
FAM167A has a leucine zipper as part of its secondary structure as noted by the four heptad leucine repeat regions shown in SAPS. The leucine zipper is a portion of the DUF domain. Predictions of the secondary structure for the FAM167A protein are mostly that it is made of alpha helices and coiled coils, which would be reasonable as there is a coiled coil domain. The C-terminus end of DUF3259 is generally agreed upon in the PELE program to be a region of potential beta sheets and coiled coils. Using PELE, there is some consensus amongst the eight different outputs given as to the general secondary structure of the protein. There are no transmembrane domains as predicted on the FAM167A protein.
## Interacting proteins
Using the MINT, STRING, and IntAct tools on Genecards, the sources have a consensus on the interactions between FAM167A and BANK1 as well as the BLK gene. These proteins are already known to interact with FAM167A in the development of several diseases such as Sjogren’s disease and systemic sclerosis. In both the case of BANK1 and BLK, there is literature to back up the possible connections and interactions between the two proteins in disease development.
## Post-translational modification
No glycosylation sites have been found, as searched using tools on Expasy.org. There was a site for serine phosphorylation on both the human and mouse proteins and two for tyrosine phosphorylation, amino acids 147, 159, and 170 respectfully. Phosphorylation sites are used for various regulatory functions such as enzyme inhibition, protein-protein interactions, and protein degradation.
# Function
Micro arrays show that FAM167A has varied expression in reactions to cancers, but no information regarding the exact function of FAM167A can be drawn from these micro arrays. FAM167A has ubiquitously low expression in all tissues types throughout the body. In mouse it has a higher expression in the skin, B-cells, and spleen, but the same low expression in all other cell types.
# Clinical significance
SNPs in the regions between FAM167A and the BLK gene have been associated with the development of Sjogren's syndrome in a Han Chinese population, as well as in a Scandinavian population. The FAM167A-BLK region has also been linked to systemic sclerosis by comparing functional variants in the C8orf13-BLK locus in a Caucasian population. Results of the study confirms the C8orf13-BLK locus as a systemic sclerosis risk locus, strongest effects were observed in the interactions between that locus and BANK1. | FAM167A
Family with sequence similarity 167, member A is a protein in humans that is encoded by the FAM167A gene located on chromosome 8.[1]
FAM167A and its paralogs are protein encoding genes containing the conserved domain DUF3259, a protein of unknown function.[2] FAM167A has many orthologs in which the domain of unknown function is highly conserved.
# Gene
## Locus
On chromosome 8, FAM167A is positioned between c8orf12 (anti-sense) and BLK (anti-sense).[3] The exact locus of FAM167A is 8p23-22 and spans from 11,278,972 to 11,332,224, a total of 53,253 base pairs. The promoter spans from 11324145 to 11324476 on the negative strand, thereby the first basepair is actually on 11324476. There are no human isoforms found.
Gene Locus
## Aliases
Family with Sequence Similarity 167, Member A is also known as FAM167A, c8orf13, or D8S265.[4]
# Homology
## Paralogs
FAM167A has one paralog, FAM167B also known as c1orf90.[5] FAM167B is located at 1p35.1 on the plus strand and is composed of 163 amino acids and also contains DUF3259.[6]
## Orthologs
FAM167A has orthologs in 82 organisms and is conserved across chimpanzees, dog, cow, mouse, chicken, rat, frogs, and zebrafish.[7][8]
As shown in the table above, FAM167A is highly conserved across many orthologs of various divergence dates. The exact degree of conservation follows what is expected due to the evolutionary track of a protein.
# Protein
## Primary sequence
The gene that encodes FAM167A is 214 amino acids in length. The molecular weight in humans of the FAM167A protein is 24.2 kdal and the isoelectric point is measured to be 5.887 in Homo sapiens.[9] Mouse and chicken orthologs were shown to have a molecular weight of ± 0.5 kdal and isoelectric points were ±0.6.
## Variants
As per the results on AceView, shown right, the FAM167A gene contains 13 introns. The gene is also "well expressed" at 1.2 times the average gene. Transcription produces 9 different mRNAs, 8 of which are alternatively spliced and 1 unspliced form. 4 of the spliced proteins, which includes 2 isoforms, are considered to be good while the remaining five are partial or not good proteins.[10]
## Secondary structure
FAM167A has a leucine zipper as part of its secondary structure as noted by the four heptad leucine repeat regions shown in SAPS. The leucine zipper is a portion of the DUF domain. Predictions of the secondary structure for the FAM167A protein are mostly that it is made of alpha helices and coiled coils, which would be reasonable as there is a coiled coil domain. The C-terminus end of DUF3259 is generally agreed upon in the PELE program to be a region of potential beta sheets and coiled coils. Using PELE, there is some consensus amongst the eight different outputs given as to the general secondary structure of the protein. There are no transmembrane domains as predicted on the FAM167A protein.
## Interacting proteins
Using the MINT, STRING, and IntAct tools on Genecards, the sources have a consensus on the interactions between FAM167A and BANK1 as well as the BLK gene.[11] These proteins are already known to interact with FAM167A in the development of several diseases such as Sjogren’s disease and systemic sclerosis. In both the case of BANK1 and BLK, there is literature to back up the possible connections and interactions between the two proteins in disease development.
## Post-translational modification
No glycosylation sites have been found, as searched using tools on Expasy.org. There was a site for serine phosphorylation on both the human and mouse proteins and two for tyrosine phosphorylation, amino acids 147, 159, and 170 respectfully. Phosphorylation sites are used for various regulatory functions such as enzyme inhibition, protein-protein interactions, and protein degradation.
# Function
Micro arrays show that FAM167A has varied expression in reactions to cancers, but no information regarding the exact function of FAM167A can be drawn from these micro arrays. FAM167A has ubiquitously low expression in all tissues types throughout the body.[12] In mouse it has a higher expression in the skin, B-cells, and spleen, but the same low expression in all other cell types.[13]
# Clinical significance
SNPs in the regions between FAM167A and the BLK gene have been associated with the development of Sjogren's syndrome in a Han Chinese population,[14] as well as in a Scandinavian population.[15] The FAM167A-BLK region has also been linked to systemic sclerosis by comparing functional variants in the C8orf13-BLK locus in a Caucasian population. Results of the study confirms the C8orf13-BLK locus as a systemic sclerosis risk locus, strongest effects were observed in the interactions between that locus and BANK1.[16] | https://www.wikidoc.org/index.php/FAM167A | |
862607e5c81ee2c851651e097a92c25f09342eb7 | wikidoc | FAM18B1 | FAM18B1
Family with sequence similarity 18 member B1 (FAM18B1) is the hypothetical protein encoded by the gene LOC51030. Evidence for this protein only exists at the transcript level. The gene is found on chromosome 17 on the cytogenetic band 17p11.2.
This gene has two paralog in the human genome, LOC201158, which is located on chromosome 17 at 17p12, and TVP23A, which is located on chromosome 16. The duplication appears to have appeared after the MRCA of humans and apes. This gene has homologs in eukaryotes as far back as Trichoplax.
# Gene
LOC51030 is highly conserved in chordates and also shows conservation in eukaryotes, including fungi and plants. It is located on Chromosome 17 at 18,684,582-18,710,026, and the most common mRNA has 7 exons.
# Protein
This gene encode a protein of 205 amino acids in length and a predicted molecular weight of 23.57 kDa. This protein is predicted to have an isoelectric point of 8.62. It contains a domain of unknown function, DUF846, and a predicted phosphoserine site. It is a multipass transmembrane protein and a member of the FAM18/TVP23 superfamily.
FAM18B1 appears to be ubiquitously expressed in all tissues, health states, and developmental stages to some level. There is also notable expression in bladder tissue. | FAM18B1
Family with sequence similarity 18 member B1 (FAM18B1) is the hypothetical protein encoded by the gene LOC51030. Evidence for this protein only exists at the transcript level. The gene is found on chromosome 17 on the cytogenetic band 17p11.2.
This gene has two paralog in the human genome, LOC201158, which is located on chromosome 17 at 17p12, and TVP23A, which is located on chromosome 16. The duplication appears to have appeared after the MRCA of humans and apes. This gene has homologs in eukaryotes as far back as Trichoplax.
# Gene
LOC51030 is highly conserved in chordates and also shows conservation in eukaryotes, including fungi and plants.[1] It is located on Chromosome 17 at 18,684,582-18,710,026,[2] and the most common mRNA has 7 exons.
# Protein
This gene encode a protein of 205 amino acids in length and a predicted molecular weight of 23.57 kDa. This protein is predicted to have an isoelectric point of 8.62. It contains a domain of unknown function, DUF846, and a predicted phosphoserine site.[3] It is a multipass transmembrane protein and a member of the FAM18/TVP23 superfamily.
FAM18B1 appears to be ubiquitously expressed in all tissues, health states, and developmental stages to some level. There is also notable expression in bladder tissue.[4] | https://www.wikidoc.org/index.php/FAM18B1 | |
57b18b843acca49ab33bda04f250d5145bd2b00e | wikidoc | FAM193A | FAM193A
Family with sequence similarity 193 member A is a protein that in humans is encoded by the FAM193A gene located on locus p16.3 of chromosome 4. FAM193A is also known as C4orf8, chromosome 4 open reading frame 8, RES4-22, protein IT143, and hypothetical protein LOC86032.
# Gene
Comparing variation of splicing throughout the FAM193A gene using Ensembl, 11 transcripts were found of which three are erroneous or truncated proteins and two being retained introns from non-CDS transcripts. All transcripts represented reveal exactly same starting point with respect to exon 1. This continuity is seen throughout the 5’UTR in all alternatively spliced mRNAs, with the exception in splice variant 4. There are three areas within the expressed protein that possibly have motifs; leucine zipper within a coiled-coil. These three motifs lie within exon 5, 16 and 17. The areas are either expressed or entirely missed and other parts are expressed.
# Tissue distribution
The gene FAM193A is most abundantly expressed, by examination of spot intensity from its EST profile Hs.652364, in the embryonic, lymph node, nerve, uterus, testis, larynx tissues and somewhat in the blood. The gene is expressed through a number of health states, for example, adrenal, chondrosarcoma and uterine tumors, it is also implicated in soft tissue/ muscle tissue tumors.
A microarray from BRAINSPAN.org within the Prenatal LCM microarray data shows high abundance of FAM193A expression in humans ubiquitously throughout the brain. One of three probes showed very little gene expression of FAM193A (A_24_P126465). The most significant structures in terms of signal intensity from the microarray are; occipital lobe, hippocampal formation, globus pallidus, parahippocampal gyrus, amygdala, but relatively little expression in the insula.
# Regulation
FAM193A has several specific chemical–gene interactions curated from published literature. Interactions with Aflatoxin,a naturally occurring mycotoxin, was looked into for carcinogenic potential evaluated through application of chronic rodent bioassays. This compound increases the expression of FAM193A mRNA and by hierarchical clustering implicates this gene in processes related to macromolecules, cellular organization, and regulation.
Dihydrotestosterone is androgen of the male sex hormone. Androgen play an important role in maintenance and growth of prostate cells. In a study using prostate cancer cell line LNCaP treated with Dihydrotestosterone and bicalutamide for 6, 24, and 48 hours, researchers registered 56 different transcripts that showed homology to transcription factors, cell cycle regulators, metabolic enzymes, and hypothetical proteins. Of these FAM193A gene expression is upregulated in the presence of Dihydrotestosterone for 48 hours.
# Structure
Using NCBI’s cBLAST five structures were found that aligned somewhat to FAM193A. Of the structures only two were too were examined Chain A, RNA Polymerase Ii from Schizosaccharomyces Pombe and Chain A Tropomyosin. Comparison with the previous structure of the enzyme from the budding yeast Saccharomyces cerevisiae reveals differences in regions implicated in start site selection and transcription factor interaction. These aspects of the transcription mechanism differ between S. pombe and S. cerevisiae, but are conserved between S. pombe and humans. Amino acid changes apparently responsible for the structural differences are also conserved between S. pombe and humans, suggesting that the S. pombe structure may be a good surrogate for that of the human enzyme.
The predicted secondary structure of FAM193A examined through predictprotein.org showed that more than ¾ of the residues exposing more than 16% of their surface. This program also shows that FAM193A is approximately ½ alpha helical.
# Protein interactions
There is a novel gene, IRIZIO that cooperates with PAX3-FOXO1 fusion gene and may contribute to rhabdomyosarcomagenesis in children. This novel gene is homologous to the FAM193 A using the National Center for Biotechnology Information Basic Local Alignment Search Tool revealed an overall homology of 53%. Furthermore, the highest similarity is in the last 76 amino acids (89% homology) of both proteins.
# Quantitative trait locus
Quantitative trait locus:
# Related genes
## Orthologs
Primates, chimp and gibbon, represented the closest group of orthologous proteins in relation to humans (E range = 0.0-0.0), these along with others were used make a multiple sequence alignment (MSA). The MSA of the closest clade to humans all fell under the same duplication event. The avian (Zebra finch, chicken, turkey) and fish (Zebra fish, Pufferfish). were the animals that had attained this protein before the duplication event. These were found by BLASTing against the human genome. RNA Transcripts searched for BLASTp against the human genome produced no results of significance. Similarly, distantly related animals were found using BLASTp, but of the protein sequences matched, only small portions correlated with FAM193A.
## Paralogs
Support for one paralog, FAM193B, shows homology to FAM193A's C-terminus end. FAM193B is 2961 nts long while FAM193A is 4710 and when aligned using Biology Workbench received a low score of -4490. | FAM193A
Family with sequence similarity 193 member A is a protein that in humans is encoded by the FAM193A gene[1] located on locus p16.3 of chromosome 4.[2] FAM193A is also known as C4orf8, chromosome 4 open reading frame 8, RES4-22, protein IT143, and hypothetical protein LOC86032.[3]
# Gene
Comparing variation of splicing throughout the FAM193A gene using Ensembl, 11 transcripts were found of which three are erroneous or truncated proteins and two being retained introns from non-CDS transcripts.[4] All transcripts represented reveal exactly same starting point with respect to exon 1. This continuity is seen throughout the 5’UTR in all alternatively spliced mRNAs, with the exception in splice variant 4. There are three areas within the expressed protein that possibly have motifs; leucine zipper within a coiled-coil. These three motifs lie within exon 5, 16 and 17. The areas are either expressed or entirely missed and other parts are expressed.
# Tissue distribution
The gene FAM193A is most abundantly expressed, by examination of spot intensity from its EST profile Hs.652364, in the embryonic, lymph node, nerve, uterus, testis, larynx tissues and somewhat in the blood.[5] The gene is expressed through a number of health states, for example, adrenal, chondrosarcoma and uterine tumors, it is also implicated in soft tissue/ muscle tissue tumors.[6]
A microarray from BRAINSPAN.org within the Prenatal LCM microarray data shows high abundance of FAM193A expression in humans ubiquitously throughout the brain. One of three probes showed very little gene expression of FAM193A (A_24_P126465). The most significant structures in terms of signal intensity from the microarray are; occipital lobe, hippocampal formation, globus pallidus, parahippocampal gyrus, amygdala, but relatively little expression in the insula.[7]
# Regulation
FAM193A has several specific chemical–gene interactions curated from published literature. Interactions with Aflatoxin,a naturally occurring mycotoxin, was looked into for carcinogenic potential evaluated through application of chronic rodent bioassays. This compound increases the expression of FAM193A mRNA and by hierarchical clustering [8] implicates this gene in processes related to macromolecules, cellular organization, and regulation.[9]
Dihydrotestosterone is androgen of the male sex hormone. Androgen play an important role in maintenance and growth of prostate cells. In a study using prostate cancer cell line LNCaP treated with Dihydrotestosterone and bicalutamide for 6, 24, and 48 hours, researchers registered 56 different transcripts that showed homology to transcription factors, cell cycle regulators, metabolic enzymes, and hypothetical proteins. Of these FAM193A gene expression is upregulated in the presence of Dihydrotestosterone for 48 hours.[10]
# Structure
Using NCBI’s cBLAST five structures were found that aligned somewhat to FAM193A. Of the structures only two were too were examined Chain A, RNA Polymerase Ii from Schizosaccharomyces Pombe and Chain A Tropomyosin. Comparison with the previous structure of the enzyme from the budding yeast Saccharomyces cerevisiae reveals differences in regions implicated in start site selection and transcription factor interaction. These aspects of the transcription mechanism differ between S. pombe and S. cerevisiae, but are conserved between S. pombe and humans. Amino acid changes apparently responsible for the structural differences are also conserved between S. pombe and humans, suggesting that the S. pombe structure may be a good surrogate for that of the human enzyme.
The predicted secondary structure of FAM193A examined through predictprotein.org showed that more than ¾ of the residues exposing more than 16% of their surface. This program also shows that FAM193A is approximately ½ alpha helical.[11]
# Protein interactions
There is a novel gene, IRIZIO that cooperates with PAX3-FOXO1 fusion gene and may contribute to rhabdomyosarcomagenesis in children. This novel gene is homologous to the FAM193 A using the National Center for Biotechnology Information Basic Local Alignment Search Tool revealed an overall homology of 53%. Furthermore, the highest similarity is in the last 76 amino acids (89% homology) of both proteins.[12]
# Quantitative trait locus
Quantitative trait locus:[13]
# Related genes
## Orthologs
Primates, chimp and gibbon, represented the closest group of orthologous proteins in relation to humans (E range = 0.0-0.0), these along with others were used make a multiple sequence alignment (MSA). The MSA of the closest clade to humans all fell under the same duplication event. The avian (Zebra finch, chicken, turkey) and fish (Zebra fish, Pufferfish). were the animals that had attained this protein before the duplication event. These were found by BLASTing against the human genome. RNA Transcripts searched for BLASTp against the human genome produced no results of significance. Similarly, distantly related animals were found using BLASTp, but of the protein sequences matched, only small portions correlated with FAM193A.
## Paralogs
Support for one paralog, FAM193B, shows homology to FAM193A's C-terminus end. FAM193B is 2961 nts long while FAM193A is 4710 and when aligned using Biology Workbench received a low score of -4490. | https://www.wikidoc.org/index.php/FAM193A | |
a3ac2111bc663e5dc0161e56ccdc0855be128190 | wikidoc | FAM200A | FAM200A
C7orf38 is a gene located on chromosome 7 in the human genome. The gene is expressed in nearly all tissue types at very low levels. Evolutionarily, it can be found throughout the kingdom animalia. While the function of the protein is not fully understood by the scientific community, bioinformatic tools have shown that the protein bares much similarity to zinc finger or transposase proteins. Many of its orthologs, paralogs, and neighboring genes have been shown to possess zinc finger domains. The protein contains a hAT dimerization domain nears its C-terminus. This domain is highly conserved in transposase enzymes.
# Gene
C7orf38 is located on chromosome 7 at q22.1. Its genomic sequence contains 5,612 bp. The predominant transcript contains two exons and is 2,507 bp in length. The translated protein contains 573 amino acids.
# Protein composition
The 573 amino acid protein has a molecular weight of 66,280.05. The isoelectric point was found to occur at a pH of 5.775, about 1.6 pH lower than that of the average human pH. Two deviations from prototypical human proteins are evident. The protein contains a less than expected number of glycine residues, and is rich in leucine residues. There are not sections of strong hydrophobicity or hydrophilicity. Thus, it is not predicted to be a transmembrane protein.
# Gene neighborhood
The four genes in closest proximity to C7orf38 on chromosome 7 exhibit similar function, many of which are transcription factors.
# Paralogs
Eight paralogs are found in the human proteome. Similar to the neighboring genes, many of the paralogs function as zinc fingers, or transcription factors.
# Orthologs
Orthologs to C7orf38 can be traced back evolutionarily through plants. The following is not an extensive list of orthologs. It is intended to provide an evolutionary overview of the conservation of C7orf38.
# Structure
## Protein
CBLast was used to determine a structurally related protein with experimentally determined structure. The protein Hermes DNA transposase, of the Hermes DBD superfamily, was shown to be structurally similar (Evalue: 1E-6).
The hAT dimerization domain is found at the C-terminus of transposase elements belonging to the Activator superfamily (hAT element superfamily). The isolated dimerization domain forms extremely stable dimers in vitro.
## mRNA
The MFOLD program available at Rensselaer BioInformatics Server was used to predict secondary structure of the mature mRNA sequence.
The primary sequence of the mRNA secondary structures displayed high levels of conservation in orthologs, suggesting structural importance.
# Tissue distribution
The gene appears to be expressed in most tissue types. Very low levels of expression were observed through est profiles, and no deviation was observed between health or developmental states. | FAM200A
C7orf38 is a gene located on chromosome 7 in the human genome.[1] The gene is expressed in nearly all tissue types at very low levels.[2] Evolutionarily, it can be found throughout the kingdom animalia. While the function of the protein is not fully understood by the scientific community, bioinformatic tools have shown that the protein bares much similarity to zinc finger or transposase proteins. Many of its orthologs, paralogs, and neighboring genes have been shown to possess zinc finger domains.[3] The protein contains a hAT dimerization domain nears its C-terminus.[4] This domain is highly conserved in transposase enzymes.[5]
# Gene
C7orf38 is located on chromosome 7 at q22.1. Its genomic sequence contains 5,612 bp. The predominant transcript contains two exons and is 2,507 bp in length.[6] The translated protein contains 573 amino acids.[7]
# Protein composition
The 573 amino acid protein has a molecular weight of 66,280.05.[8] The isoelectric point was found to occur at a pH of 5.775, about 1.6 pH lower than that of the average human pH.[9] Two deviations from prototypical human proteins are evident. The protein contains a less than expected number of glycine residues, and is rich in leucine residues.[10] There are not sections of strong hydrophobicity or hydrophilicity. Thus, it is not predicted to be a transmembrane protein.
# Gene neighborhood
The four genes in closest proximity to C7orf38 on chromosome 7 exhibit similar function, many of which are transcription factors.[11]
# Paralogs
Eight paralogs are found in the human proteome.[3] Similar to the neighboring genes, many of the paralogs function as zinc fingers, or transcription factors.
# Orthologs
Orthologs to C7orf38 can be traced back evolutionarily through plants.[3] The following is not an extensive list of orthologs. It is intended to provide an evolutionary overview of the conservation of C7orf38.
# Structure
## Protein
CBLast was used to determine a structurally related protein with experimentally determined structure. The protein Hermes DNA transposase, of the Hermes DBD superfamily, was shown to be structurally similar (Evalue: 1E-6).[12]
The hAT dimerization domain is found at the C-terminus of transposase elements belonging to the Activator superfamily (hAT element superfamily). The isolated dimerization domain forms extremely stable dimers in vitro.[5]
## mRNA
The MFOLD program available at Rensselaer BioInformatics Server was used to predict secondary structure of the mature mRNA sequence.[13]
The primary sequence of the mRNA secondary structures displayed high levels of conservation in orthologs, suggesting structural importance.
# Tissue distribution
The gene appears to be expressed in most tissue types.[14] Very low levels of expression were observed through est profiles, and no deviation was observed between health or developmental states. | https://www.wikidoc.org/index.php/FAM200A | |
8d35e78330a58cb744c2749d12f5abade35b8406 | wikidoc | FAM203B | FAM203B
Family with Sequence Similarity 203, Member B (FAM203B) is a protein encoded by the FAM203B gene (8q24.3) in humans. While FAM203B is only found in humans and possibly non-human primates, its paralog, FAM203A, is highly conserved. The FAM203B protein contains two conserved domains of unknown function, DUF383 and DUF384, and no transmembrane domains. This protein has no known function yet, although the homolog of FAM203A in Caenorhabditis elegans (Y54H5A.2) is thought to help regulate the actin cytoskeleton.
# Gene
FAM203B is located on the positive DNA strand of the long arm of chromosome 8 at locus 24.3 (8q24.3) from 76,368,898 - 76,371,411 in the human genome. The gene product contains 2,402 bp of mRNA with 6 predicted exons in the human gene. There are no known isoforms.
## Gene Neighborhood
The pseudogene TSSK5P2 is located on the negative strand opposite FAM203B (145,440,975 - 145,443,775), while LOC377711 is located immediately downstream on the positive strand (145,448,755 - 145,485,896). FAM203A, MROH1, and SCXB are located upstream of FAM203B.
## Gene Expression
Expression Profile: mRNA expression has been localized in many tissue types (immune, nervous, muscle, internal, secretory, and reproductive) in similar quantities and may therefore be ubiquitous.
Promoter: The predicted promoter region of FAM203B is located between 145,437,380 and 145,438,015 on Chromosome 8 and has a length of 636 bp.
# Protein
The function of FAM203B is not currently understood. The FAM203B protein has 390 amino acids, a molecular weight of 42.1 kdal, and an isoelectric point of 4.56.
## Structure
FAM203B contains two domains of unknown function: DUF383 (residues 110-288) and DUF384 (residues 292-349). The protein is alanine-, proline-, and leucine-rich, but poor in serine, asparagine, threonine, isoleucine, lysine, and phenylalanine. The following internal repeats can be found in the primary sequence: LPFL (26-29, 245-248), ELAP (70-73), GRAL (54-57, 111-114), and LAADPGL (88-94, 99-105). There are no positive, negative, mixed charge, or hydrophobic clusters; no transmembrane domains; and no clusters of amino acid multiplets. The secondary structure prediction generated by the Phyre 2.0 bioinformatic server shows only α-helices, almost all of which have high confidence values. The overall confidence value of the model is 99.5%.
## Post-Translational Modifications
There are at least six predicted phosphorylation sites in FAM203B: S17, S153, Y167, T223, S259, and S320. The FAM203B protein is also predicted to locate to the cytoplasm.
## Protein Interactions
There are many possible transcription factor binding sites in the FAM203B promoter. Below is a table of the best possibilities, which have high confidence values, evolutionary conservation, and/or multiple possible binding sites in the promoter.
Table of Possible Transcription Factor Binding Sites in Predicted FAM203B Promoter:
There are several other proteins that may interact directly with the FAM203B protein including C1orf112, HEATR3, MRTO4, BYSL, GINS1, DKC1, TXNDC12, PWP2, IMP4, and NIP7.
# Homology and Evolution
## FAM203A: Paralog
FAM203A is 99% identical to FAM203B with only one amino acid difference (E264Q) due to a point mutation (G857C). This indicates that the duplication event that produced FAM203B 242,266 bp downstream from FAM203A occurred very recently in evolutionary history. The FAM203A protein is highly conserved and has orthologs in primates, rodents, ungulates, marsupials, amphibians, fish, fungi, plants, and at least one monotreme, one reptile, and one hemichordate.
## Orthologs and Homologs
Table of FAM203B Paralog and Homologs:
There is one ortholog of FAM203B, brain protein 16-like (BRP16L) in Macaca mulatta, although no other primates appear to have orthologous proteins. There are two possible explanations for this anomaly: (1) DNA of other primates has not been sequenced thoroughly in the genomic region of the FAM203B ortholog, or (2) FAM203B is the result of a gene duplication event unique to humans, meaning that BRP16L in M. mulatta resulted from an earlier duplication event unique to that species. The second explanation is supported by the following evidence:
- Like M. mulatta, Danio rerio has both a FAM203A gene and a BRP16L gene. The large amount of time since the divergence of the M. mulatta and D. rerio lineages suggests that these BRP16L genes are the result of separate duplication events.
- The BRP16L protein in D. rerio has a significant 3’ truncation compared to the M. mulatta protein, further supporting the hypothesis that these proteins evolved separately.
- If the BRP16L genes in "M mulatta" and "D. rerio" are the result of separate duplication events, then it is also possible that FAM203B and BRP16L in "M. mulatta" are the result of separate duplication events.
- BRP16 (brain protein 16) is an alias of FAM203A, and BRP16L (brain protein 16-like) is an alias of FAM203B. A gene named BRP16L simply means that the gene is related to FAM203A but not necessarily to FAM203B.
- FAM203A and FAM203B are located in the telomeric region of chromosome 8, an area of chromosomes that frequently experiences recombination events.
However, because FAM203A and FAM203B are so similar, it is difficult to determine whether proteins are orthologs or just simply homologs.
## Phylogeny
The phylogenetic tree of FAM203B and its homologs matches with the overall divergence of the respective lineages.
## Conserved Domains, Motifs, and Residues
- ARM (armadillo/beta-catenin-like repeats-containing): Found in two homologs (FAM203A in Danio rerio and At1g14300 in Arabidopsis thaliana) and overlaps slightly with the beginning of the DUF383 domain. Related to the HEAT domain, consists of a 40-amino-acid tandemly repeated sequence motif, and is thought to mediate protein-protein interactions. Several eukaryotic genes contain ARM domains including armadillo in Drosophila melanogaster, beta-catenin, plakoglobin, and adenomatous polyposis coli in mammals.
- DUF383: Domain of unknown function 383
- DUF384: Domain of unknown function 383
Every ortholog and homolog of FAM203B has a DUF383 domain and a DUF384 domain (except Anolis carolinensis, which is missing DUF384 due to a large 3' truncation). There is significant variation among mammals, marsupials, and monotremes as to where the DUF383 domain begins, whereas this variation is smaller in reptiles, amphibians, fish, invertebrates, plants, and fungi. Additionally, the DUF383 domain ends at the same location for all homologs, while the DUF384 domain starts and ends at roughly the same location in all homologs. There is high homology in the DUF384 domain (292..349) and in the DUF383 domain (154..288), and several amino acids are completely conserved in vertebrates, invertebrates, plants, and fungi, which include Arg190, Gly219, Asn226, Lys273, and Lys338. Other highly conserved amino acids include Asn87, Lys88, Arg216, and Phe229. | FAM203B
Family with Sequence Similarity 203, Member B (FAM203B) is a protein encoded by the FAM203B gene (8q24.3) in humans.[1][2] While FAM203B is only found in humans and possibly non-human primates, its paralog, FAM203A,[3] is highly conserved.[4] The FAM203B protein contains two conserved domains of unknown function, DUF383 and DUF384,[4] and no transmembrane domains.[5] This protein has no known function yet, although the homolog of FAM203A in Caenorhabditis elegans (Y54H5A.2) is thought to help regulate the actin cytoskeleton.[6]
# Gene
FAM203B is located on the positive DNA strand of the long arm of chromosome 8 at locus 24.3 (8q24.3) from 76,368,898 - 76,371,411 in the human genome. The gene product contains 2,402 bp of mRNA with 6 predicted exons in the human gene.[2][7] There are no known isoforms.
## Gene Neighborhood
The pseudogene TSSK5P2 is located on the negative strand opposite FAM203B (145,440,975 - 145,443,775),[9] while LOC377711 is located immediately downstream on the positive strand (145,448,755 - 145,485,896).[10] FAM203A, MROH1, and SCXB are located upstream of FAM203B.[7][11]
## Gene Expression
Expression Profile: mRNA expression has been localized in many tissue types (immune, nervous, muscle, internal, secretory, and reproductive) in similar quantities and may therefore be ubiquitous.[8]
Promoter: The predicted promoter region of FAM203B is located between 145,437,380 and 145,438,015 on Chromosome 8 and has a length of 636 bp.[12]
# Protein
The function of FAM203B is not currently understood. The FAM203B protein has 390 amino acids,[1] a molecular weight of 42.1 kdal,[5] and an isoelectric point of 4.56.[13]
## Structure
FAM203B contains two domains of unknown function: DUF383 (residues 110-288) and DUF384 (residues 292-349).[1] The protein is alanine-, proline-, and leucine-rich, but poor in serine, asparagine, threonine, isoleucine, lysine, and phenylalanine. The following internal repeats can be found in the primary sequence: LPFL (26-29, 245-248), ELAP (70-73), GRAL (54-57, 111-114), and LAADPGL (88-94, 99-105). There are no positive, negative, mixed charge, or hydrophobic clusters; no transmembrane domains; and no clusters of amino acid multiplets.[5] The secondary structure prediction generated by the Phyre 2.0 bioinformatic server shows only α-helices, almost all of which have high confidence values. The overall confidence value of the model is 99.5%.[14]
## Post-Translational Modifications
There are at least six predicted phosphorylation sites in FAM203B: S17, S153, Y167, T223, S259, and S320.[15] The FAM203B protein is also predicted to locate to the cytoplasm.[16]
## Protein Interactions
There are many possible transcription factor binding sites in the FAM203B promoter. Below is a table of the best possibilities, which have high confidence values, evolutionary conservation, and/or multiple possible binding sites in the promoter.[12]
Table of Possible Transcription Factor Binding Sites in Predicted FAM203B Promoter:[12]
There are several other proteins that may interact directly with the FAM203B protein including C1orf112, HEATR3, MRTO4, BYSL, GINS1, DKC1, TXNDC12, PWP2, IMP4, and NIP7.[17]
# Homology and Evolution
## FAM203A: Paralog
FAM203A is 99% identical to FAM203B with only one amino acid difference (E264Q) due to a point mutation (G857C).[1][11][18] This indicates that the duplication event that produced FAM203B 242,266 bp downstream[7] from FAM203A occurred very recently in evolutionary history. The FAM203A protein is highly conserved and has orthologs in primates, rodents, ungulates, marsupials, amphibians, fish, fungi, plants, and at least one monotreme, one reptile, and one hemichordate.[4][19]
## Orthologs and Homologs
Table of FAM203B Paralog and Homologs:
There is one ortholog of FAM203B, brain protein 16-like (BRP16L) in Macaca mulatta,[4][19] although no other primates appear to have orthologous proteins. There are two possible explanations for this anomaly: (1) DNA of other primates has not been sequenced thoroughly in the genomic region of the FAM203B ortholog, or (2) FAM203B is the result of a gene duplication event unique to humans, meaning that BRP16L in M. mulatta resulted from an earlier duplication event unique to that species. The second explanation is supported by the following evidence:
- Like M. mulatta, Danio rerio has both a FAM203A gene and a BRP16L gene. The large amount of time since the divergence of the M. mulatta and D. rerio lineages suggests that these BRP16L genes are the result of separate duplication events.
- The BRP16L protein in D. rerio has a significant 3’ truncation compared to the M. mulatta protein, further supporting the hypothesis that these proteins evolved separately.[18][21][22]
- If the BRP16L genes in "M mulatta" and "D. rerio" are the result of separate duplication events, then it is also possible that FAM203B and BRP16L in "M. mulatta" are the result of separate duplication events.
- BRP16 (brain protein 16) is an alias of FAM203A, and BRP16L (brain protein 16-like) is an alias of FAM203B. A gene named BRP16L simply means that the gene is related to FAM203A but not necessarily to FAM203B.
- FAM203A and FAM203B are located in the telomeric region of chromosome 8, an area of chromosomes that frequently experiences recombination events.
However, because FAM203A and FAM203B are so similar, it is difficult to determine whether proteins are orthologs or just simply homologs.
## Phylogeny
The phylogenetic tree of FAM203B and its homologs matches with the overall divergence of the respective lineages.[18][20]
## Conserved Domains, Motifs, and Residues
- ARM (armadillo/beta-catenin-like repeats-containing): Found in two homologs (FAM203A in Danio rerio and At1g14300 in Arabidopsis thaliana) and overlaps slightly with the beginning of the DUF383 domain. Related to the HEAT domain, consists of a 40-amino-acid tandemly repeated sequence motif, and is thought to mediate protein-protein interactions. Several eukaryotic genes contain ARM domains including armadillo in Drosophila melanogaster, beta-catenin, plakoglobin, and adenomatous polyposis coli in mammals.[4]
- DUF383: Domain of unknown function 383
- DUF384: Domain of unknown function 383
Every ortholog and homolog of FAM203B has a DUF383 domain and a DUF384 domain (except Anolis carolinensis, which is missing DUF384 due to a large 3' truncation[19][23]). There is significant variation among mammals, marsupials, and monotremes as to where the DUF383 domain begins, whereas this variation is smaller in reptiles, amphibians, fish, invertebrates, plants, and fungi. Additionally, the DUF383 domain ends at the same location for all homologs, while the DUF384 domain starts and ends at roughly the same location in all homologs. There is high homology in the DUF384 domain (292..349) and in the DUF383 domain (154..288), and several amino acids are completely conserved in vertebrates, invertebrates, plants, and fungi, which include Arg190, Gly219, Asn226, Lys273, and Lys338. Other highly conserved amino acids include Asn87, Lys88, Arg216, and Phe229.[4][18] | https://www.wikidoc.org/index.php/FAM203B | |
c554cf3aa326145285cb61e887a071f5b47df999 | wikidoc | FAM208b | FAM208b
Protein FAM208B (family with sequence similarity 208 member b) is a protein that in humans is encoded by the FAM208B gene. The gene is also known as "chromosome 10 open reading frame 18" (c10orf18). FAM208B is expressed throughout the body however its function has not been established. FAM208b has been observed to be differentially regulated in various cancers and throughout developmen. While the exact role of the protein is yet to be established, the significant presence of the protein within humans and throughout the phylogenetic tree depicts a central importance of the gene in normal function.
# Gene
The gene is located on chromosome 10 at position 10p15.1. FAM208b is upstream of ankryn repeat and SOCS box containing 13 (ASB13), and downstream of the GDP dissociation inhibitor 2 (GDI2) and nuclear receptor binding factor 2 pseudogene 5 (NRBF2P5). ASBI13 and GDI2 are both found on the opposite strand of FAM208b, while NRBF2P5 is on the same strand.
# Homology and Evolution
## Paralog
FAM208b has a single paralog, FAM208a. FAM208a is also known as "retinoblastoma-associated protein 140", "Transgene Activation Suppression Protein" (TASOR), "CTCL Tumor Antigen", and "chromosome 3 open reading frame 63" (c3orf63).
## Orthologs
FAM208b is conserved only in vertebrates. Orthologs can be found in mammals, reptiles, and amphibians. Distant homologs, including orthologs of the paralog, FAM208a, are observed in bony fish and sharks.
## Homologous Domains
FAM208b has highly conserved N- and C- termini and a less conserved central region. Three domains of unknown function (DUFs) are found within the protein, including one DUF 3699 and two DUF 3715. All three DUFs are conserved between species. DUF 3715 is found in the paralog of FAM208b.
## Evolution
The change in amino acids over time of FAM208b indicates that it is a rapidly evolving gene. The presence of FAM208a but not FAM208b in bony fish and sharks but not FAM208b, indicates that the paralogs split about 325 million years ago.
# Transcription
## Promoter
Two promoter regions for FAM208b can be observed. The earlier promoter region is regulated by numerous transcription factors. The promoter contains binding sites for Ikaros2, Nuclear Factor Y, and at least three binding sites for Pleomorphic adenoma gene 1.
The second promoter region is found within the first intron and encodes a slightly shorter mRNA. This promoter contains multiple binding sites for the FOXP1 transcription factor.
## mRNA
The mRNA of the most common peptide (variant x2) is 8699 nucleotides long and includes 22 exons.
### Binding Proteins
The 5' UTR is bound by the RNA binding proteins RBMX1, FUS, SFRS1, ACO1, and NONO. The 3' UTR is bound by EIF4B, A2BP1, and ZFP36. A single non-coding variant of FAM208b is transcribed. This sequence is partially complimentary to the human gene PCNX1.
## Transcript Variants
A total of 20 transcript variants of FAM208b, including one non-coding RNA have been observed. While multiple splice variants are present, 18 exons, composing for 7089 base pairs that code for 2331 amino acids, are present in all coding variants. This constitutes approximately 82.1% of the most common transcript variant (X2), and 95.6% of its polypeptide product. The most commonly skipped exon is Exon 12 (position ch10: 5735304-5735546). Multiple variants have alternative transcription start sites, indicative of an internal promoter sequence.
# Protein
## Biochemistry
The primary isoform of FAM208b consists of 2430 amino acids. The total molecular weight is 268.86 kD. FAM208b has an isoelectric point of 5.72. FAM208b has an instability index of 53.64, making it a relatively unstable protein in the unphosphorylated form.
## Primary Structure
FAM208b has a unique amino acid composition. An above-average proportion of serine residues are observed (11.1%). This indicates a potential role in intracellular signaling.
## Secondary Structure
FAM208b is predicted to have multiple alpha-helical domains. It is predicted that 25% of the protein forms alpha-helices, 15% forms beta-strands, and 60% is random coil. The various DUF domains are predicted to have variable structure. DUF3699 consists of two helices and four beta-strands. The N-terminal DUF3715 appears to form a stretch of random coil, while the C-terminal DUF3715 has two helices and four beta-strands.
## Tertiary Structure
A tertiary structure has not yet been confirmed by X-ray crystallography. Predictions of tertiary structure indicate a modular protein, composed of three modules connected by random coil.
## Post-Translational Modifications
### Phosphorylation
FAM208b has 13 experimentally confirmed phosphorylation sites on serine residues. The high serine content of FAM208b suggests a role in intracellular signaling.
### SUMOylation
FAM208b has potential for SUMOylation SUMOylation has been observed to play a role in nuclear transport, which would aid FAM208b's localization prediction.
### Glycosylation
FAM208b is predicted to be an intracellular protein, indicating that it is not glycosylated.
## SubCellular Location
FAM208b is predicted to be localized to the cytosol or nucleus. The peptide sequence lacks a signal sequence either at the N-terminus or internally. No transmembrane domains have been observed or predicted, indicating that FAM208b is not secreted or found in the cell membrane, and is very likely to be intracellular. A Nuclear Localization Signal is observed at amino acids 393-403. The NLS is highly conserved in mammals, birds, and reptiles.
# Clinical Significance
## Development
FAM208b expression is observed to decrease over the course of development. Peak expression is observed in the blastocyst. A sharp decline in expression is observed at the fetal stage, after which expression is maintained at constant levels through adulthood.
## Pathology
FAM208b has been observed to be correlated in a variety of cancers. The locus of FAM208b (10p15.1) was identified as an aberration site present in translocation-positive Follicular lymphoma but not Nodal Marginal Zone Lymphoma. FAM208b has also been identified as being upregulated significantly and prominently in Non-Hodgkin lymphoma cells. FAM208b has been identified as a hub gene of Stage IV colorectal cancer. A fusion of FAM208b and PLEKHB1 has been validated as candidate for fusion of chromosomes 10 and 11 in Donor Cell Leukemia.
FAM208b has also been separately observed to be differentially expressed in a variety of cancers. A decrease in transcription of FAM208b has been observed in adrenal cancer, bladder cancer, breast cancer, gastrointestinal cancer, glial cancer, kidney cancer, lymph cancer, skin cancer, muscle cancer, and uterine cancer. An increase in transcription of FAM208b has been observed in cervical cancer, leukemia, liver cancer, lung cancer, and prostate cancer.
FAM208b has also been found to be expressed at higher levels in Acute Macular Degeneration.
FAM208b has been observed to be downregulated in bronchial epithelial cells infected by respiratory syncytial virus and has been postulated as a biosignature of the infection. | FAM208b
Protein FAM208B (family with sequence similarity 208 member b) is a protein that in humans is encoded by the FAM208B gene. The gene is also known as "chromosome 10 open reading frame 18" (c10orf18). FAM208B is expressed throughout the body however its function has not been established. FAM208b has been observed to be differentially regulated in various cancers and throughout developmen. While the exact role of the protein is yet to be established, the significant presence of the protein within humans and throughout the phylogenetic tree depicts a central importance of the gene in normal function.
# Gene
The gene is located on chromosome 10 at position 10p15.1.[1] FAM208b is upstream of ankryn repeat and SOCS box containing 13 (ASB13), and downstream of the GDP dissociation inhibitor 2 (GDI2) and nuclear receptor binding factor 2 pseudogene 5 (NRBF2P5).[1] ASBI13 and GDI2 are both found on the opposite strand of FAM208b, while NRBF2P5 is on the same strand.
# Homology and Evolution
## Paralog
FAM208b has a single paralog, FAM208a. FAM208a is also known as "retinoblastoma-associated protein 140", "Transgene Activation Suppression Protein" (TASOR), "CTCL Tumor Antigen", and "chromosome 3 open reading frame 63" (c3orf63).[2]
## Orthologs
FAM208b is conserved only in vertebrates.[3] Orthologs can be found in mammals, reptiles, and amphibians. Distant homologs, including orthologs of the paralog, FAM208a, are observed in bony fish and sharks.
## Homologous Domains
FAM208b has highly conserved N- and C- termini and a less conserved central region. Three domains of unknown function (DUFs) are found within the protein, including one DUF 3699 and two DUF 3715. All three DUFs are conserved between species. DUF 3715 is found in the paralog of FAM208b.[4]
## Evolution
The change in amino acids over time of FAM208b indicates that it is a rapidly evolving gene. The presence of FAM208a but not FAM208b in bony fish and sharks but not FAM208b, indicates that the paralogs split about 325 million years ago.
# Transcription
## Promoter
Two promoter regions for FAM208b can be observed. The earlier promoter region is regulated by numerous transcription factors.[5] The promoter contains binding sites for Ikaros2, Nuclear Factor Y, and at least three binding sites for Pleomorphic adenoma gene 1.
The second promoter region is found within the first intron and encodes a slightly shorter mRNA.[1] This promoter contains multiple binding sites for the FOXP1 transcription factor.
## mRNA
The mRNA of the most common peptide (variant x2) is 8699 nucleotides long and includes 22 exons.[6][7][8][9][10]
### Binding Proteins
The 5' UTR is bound by the RNA binding proteins RBMX1, FUS, SFRS1, ACO1, and NONO. The 3' UTR is bound by EIF4B, A2BP1, and ZFP36.[11] A single non-coding variant of FAM208b is transcribed. This sequence is partially complimentary to the human gene PCNX1.
## Transcript Variants
A total of 20 transcript variants of FAM208b, including one non-coding RNA have been observed.[1] While multiple splice variants are present, 18 exons, composing for 7089 base pairs that code for 2331 amino acids, are present in all coding variants. This constitutes approximately 82.1% of the most common transcript variant (X2), and 95.6% of its polypeptide product. The most commonly skipped exon is Exon 12 (position ch10: 5735304-5735546). Multiple variants have alternative transcription start sites, indicative of an internal promoter sequence.
# Protein
## Biochemistry
The primary isoform of FAM208b consists of 2430 amino acids. The total molecular weight is 268.86 kD.[12] FAM208b has an isoelectric point of 5.72.[13] FAM208b has an instability index of 53.64,[14] making it a relatively unstable protein in the unphosphorylated form.
## Primary Structure
FAM208b has a unique amino acid composition. An above-average proportion of serine residues are observed (11.1%). This indicates a potential role in intracellular signaling.[15]
## Secondary Structure
FAM208b is predicted to have multiple alpha-helical domains.[16] It is predicted that 25% of the protein forms alpha-helices, 15% forms beta-strands, and 60% is random coil. The various DUF domains are predicted to have variable structure. DUF3699 consists of two helices and four beta-strands. The N-terminal DUF3715 appears to form a stretch of random coil, while the C-terminal DUF3715 has two helices and four beta-strands.
## Tertiary Structure
A tertiary structure has not yet been confirmed by X-ray crystallography. Predictions of tertiary structure indicate a modular protein, composed of three modules connected by random coil.
## Post-Translational Modifications
### Phosphorylation
FAM208b has 13 experimentally confirmed phosphorylation sites on serine residues.[17][18][19][20] The high serine content of FAM208b suggests a role in intracellular signaling.
### SUMOylation
FAM208b has potential for SUMOylation[21] SUMOylation has been observed to play a role in nuclear transport, which would aid FAM208b's localization prediction.
### Glycosylation
FAM208b is predicted to be an intracellular protein, indicating that it is not glycosylated.
## SubCellular Location
FAM208b is predicted to be localized to the cytosol or nucleus. The peptide sequence lacks a signal sequence either at the N-terminus or internally.[22] No transmembrane domains have been observed or predicted,[23] indicating that FAM208b is not secreted or found in the cell membrane, and is very likely to be intracellular. A Nuclear Localization Signal is observed at amino acids 393-403.[24] The NLS is highly conserved in mammals, birds, and reptiles.
# Clinical Significance
## Development
FAM208b expression is observed to decrease over the course of development.[25] Peak expression is observed in the blastocyst. A sharp decline in expression is observed at the fetal stage, after which expression is maintained at constant levels through adulthood.
## Pathology
FAM208b has been observed to be correlated in a variety of cancers. The locus of FAM208b (10p15.1) was identified as an aberration site present in translocation-positive Follicular lymphoma but not Nodal Marginal Zone Lymphoma.[26] FAM208b has also been identified as being upregulated significantly and prominently in Non-Hodgkin lymphoma cells.[27] FAM208b has been identified as a hub gene of Stage IV colorectal cancer.[28] A fusion of FAM208b and PLEKHB1 has been validated as candidate for fusion of chromosomes 10 and 11 in Donor Cell Leukemia.[29]
FAM208b has also been separately observed to be differentially expressed in a variety of cancers. A decrease in transcription of FAM208b has been observed in adrenal cancer, bladder cancer, breast cancer, gastrointestinal cancer, glial cancer, kidney cancer, lymph cancer, skin cancer, muscle cancer, and uterine cancer. An increase in transcription of FAM208b has been observed in cervical cancer, leukemia, liver cancer, lung cancer, and prostate cancer.[30]
FAM208b has also been found to be expressed at higher levels in Acute Macular Degeneration.[31][32]
FAM208b has been observed to be downregulated in bronchial epithelial cells infected by respiratory syncytial virus and has been postulated as a biosignature of the infection.[33] | https://www.wikidoc.org/index.php/FAM208b | |
d4c4701941fa40f012abb0cfbadbba979c092196 | wikidoc | FAM214A | FAM214A
Protein FAM214A, also known as protein family with sequence similarity 214, A (FAM214A) is a protein that, in humans, is encoded by the FAM214A gene. FAM214A is a gene with unknown function found at the q21.2-q21.3 locus on Chromosome 15 (human). The protein product of this gene has two conserved domains, one of unknown function (DUF4210) and another one called Chromosome_Seg. Although the function of the FAM214A protein is uncharacterized, both DUF4210 and Chromosome_Seg have been predicted to play a role in chromosome segregation during meiosis.
# Gene
## Overview
The FAM214A gene is located on the negative DNA strand (see Sense (molecular biology)) of chromosome 15 between position 52,873,514 and 53,002,014; thus making the gene 97,303 base pairs (bp) long. FAM214A has been previously labeled with two other aliases, known as KIAA1370 and FLJ10980. The FAM214A gene is predicted to contain 12 exons which comprise the final 4231 bp mRNA transcript after transcription has occurred. It is this mRNA product that is then translated into the final FAM214A protein with the help of the promoter sequence and transcription factors. The promoter for the FAM214A mRNA sequence was predicted and analyzed by the El Dorado program on Genomatix. This promoter is 601 base pairs long and spans a portion of the 5' UTR.
## Gene expression
FAM214A is considered to be ubiquitously expressed (or very nearly so) in low levels according to a number of sources such as BioGPS and the Expression Atlas. As can be seen in the BioGPS image below, there is a significantly higher expression level in immune-related cells and tissues, thus suggesting an immune role; however, there has been no specific in situ evidence to support this claim. Expression data has been collected from a number of studies performed on a large range of genes, therefore, some of the data is contradictory in nature.
# Protein
## Overview
The function of the FAM214A protein in humans is still unknown; however, there are three functional term associations including "biological process," "cellular component," and molecular function," that describe the function of this protein on The Gene Ontology which predict implications of its primary function in vivo. The protein product of FAM214A consists of 1076 amino acids (aa), has been predicted to have a molecular mass of 121,700 Daltons, and has an isoelectric point around pH 7.7. This protein is predicted to remain in the nucleus after transcription based upon its lack of signal peptide sequence and the predictions of the program PSORTII. Due to alternative splicing, two other isoforms (Q32MH5-2 and Q32MH5-3) have been observed. They differ slightly from the primary product. Isoform 2 has four different amino acids from bases 960-960 and is missing the end of the sequence from bases 964-1076. Isoform 3 has seven extra amino acids added to the beginning of the sequence after the methionine.
After being translated, the FAM214A protein is predicted to remain in the nucleus by more than one type of subprogram on PSORT II. This protein has a pat4 signal, one of the two "classical" nuclear localization signals (NLSs), starting at residue 709. Although it does not have the second "classical" NLS, pat7, nor the "non-classical" bipartite NLS it is still predicted to be targeted for the nucleus by the NCNN score. This score predicts whether the protein is targeted for the nucleus or the cytoplasm based upon the amino acid sequence. For the FAM214A protein, the NCNN score predicted nuclear localization with 94.1% certainty. Based upon this information, PSORT generates an overall prediction of the protein's subcellular localization. For FAM214A, the predicted values were 69.6% for the nucleus as compared to 13.0% for the mitochondria, 8.7% for the cytoplasm, and 4.3% for the secretory vesicles and endoplasmic reticulum.
## Post-translational modifications
This protein most likely does not undergo a significant number of post-translational modifications due to the lack of signal peptide sequence predicted by NetNGlyc and NetOGlyc on the ExPASy web server. This is because much of the intracellular machinery performing post-translational modifications requires the protein to move through organelles such as the endoplasmic reticulum and Golgi apparatus. Without a signal peptide sequence, the protein generally does not leave the nucleus, which was predicted by PSORT II as described above.
A SAPS analysis of this protein was performed against the swp23s.q database, which indicated the presence of an abnormally large number of serine amino acids and an abnormally small number of alanine amino acids in this protein. According to a review article by Fayard et al., phosphoinositide-dependent kinase 2 (PDK2) is a serine/threonine kinase that is important for regulating cell cycle. Because the FAM214A protein has a larger number of serine groups than is considered normal, there is the possibility that PDK2 has an important effect on this protein. In order to determine whether the excessive number of serines were actually predicted to be phosphorylated, the protein sequence was run through the program NetPhos from the ExPASy webserver. This program predicted the phosphorylation of 69 serines, 14 threonines, and 9 tyrosines. According to the SAPS analysis from above, there are a total or 134 serines, thus indicating that approximately half are predicted to be phosphorylated in vivo. A diagram of the phosphorylation predictions is shown to the right.
One other type of post-translational modification was predicted for the FAM214A protein by the program NetCorona on ExPASy. The program predicted a single cleavage site between position 214 and 215 in the FAM214A protein sequence after translation.
## Protein interactions
There are number of transcription factor binding sites predicted for the FAM214A promoter sequence. A few of the ones with the highest predicted confidence are provided in the table below.
Possible Transcription Factors Predicted to Bind to the FAM214A Promoter Sequence
The only protein predicted according STRING to interact with the FAM214A protein is called MFSD6L. This protein belongs to the major facilitator superfamily is predicted to be a transmembrane protein. Like FAM214A, the function of this protein has not yet been characterized through experimentation or research. Because this MFSD6L protein is the only FAM214A protein interaction predicted with any certainty, the sequence for it was run through the PSORT II program. The data from the NLS subprogram predicted the presence of a single pat4 and two pat7 NLS sequences, thus indicating possible nuclear localization. The NCNN score, on the other hand, predicted cytoplasmic localiztion with 94.1% certainty, thus leaving the overall PSORT II score at 39.1% plasma membrane, 39.1% endoplasmic reticulum, 4.3% vacuolar, 4.3% vesicles of secretory system, 4.3% Golgi, 4.3% mitochondrial, and 4.3% nuclear. This is contradictory as there are three total nuclear localization signals, but this may be due to the fact that the significant transmembrane nature of the MFSD6L protein may be causing issues with these predictions.
## Secondary and tertiary structure
The secondary structure of the FAM214A protein consists of a number of alpha helices and beta sheets as predicted by Biology Workbench and Protein Homology/analogY Recognition Engine (PHYRE). The PHYRE program predicts that 66 percent of the FAM214A secondary structure is disordered and therefore unable to be analyzed and converted into a tertiary structure prediction. It was; however, able to predict approximately 10 percent of the protein's structure with 95 percent significance. The diagram for this is shown to the left.
# Conservation
## Paralog
A single paralogous gene has been found on chromosome 9 in Homo sapiens and is named FAM214B (family with sequence similarity, B). FAM214B, although considered a paralog, has a significantly different protein sequence from that of FAM214A. When the two were compared against each other on NCBI’s BLAST, the only significant similarity observed was within the last 200 amino acids (where the DUF4210 and Chromosome_Seg domains are located). Although the similarity between FAM214A and B is low, these two proteins are in the same protein family and contain the same two conserved domains.
## Orthologs
The FAM214A protein has a significant number of orthologs across a large number of taxonomic groups including Mammalia, Aves, Reptilia, Amphibia, Actinopterygii, Echinoidea, Insecta, Trematoda, Crustacea, Tricoplacia, Anthozoa, and Eurotiomycetes. This indicates that the FAM214A protein is well conserved within Eukaryotes but does not appear to be conserved in Bacteria or Archaea. In all orthologs, the most-conserved region was near the end of the protein where the conserved domains are (see below). Orthologs for the human FAM214A protein were found as far back as Tuber melanosporum, Talaromyces stipitatus, and Aspergillus nidulans, which all diverged approximately 1215 million years ago.
Orthologs for the FAM214A Protein
## Phylogeny
An unrooted phylogenetic tree of 20 orthologs was generated by the CLUSTALW program on Biology Workbench to demonstrate the evolutionary relationship between FAM214A and its orthologs.
## Conserved domains
Within the FAM214A protein, there are three well-conserved regions. These include a well-conserved region near the n-terminus of the protein and two conserved domains including the Domain of Unknown Function 4210 (DUF4210) and a Chromosome_Seg domain near the c-terminus. A schematic diagram of these three regions is shown below. The well-conserved region near the n-terminus of the protein is not predicted to contain any known domains or motifs; however, the cleavage site predicted by NetCorona above is located within this region and it is well-conserved in a majority of the proteins orthologous to FAM214A. The two conserved domains located at the end of this protein are the most important portion of the peptide based upon evolutionary history. All organisms in the Ortholog table above except the platypus (which is missing the Chromosome_Seg domain) contain both of these conserved domains within their protein sequence. | FAM214A
Protein FAM214A, also known as protein family with sequence similarity 214, A (FAM214A) is a protein that, in humans, is encoded by the FAM214A gene. FAM214A is a gene with unknown function found at the q21.2-q21.3 locus on Chromosome 15 (human).[1] The protein product of this gene has two conserved domains, one of unknown function (DUF4210) and another one called Chromosome_Seg.[2] Although the function of the FAM214A protein is uncharacterized, both DUF4210 and Chromosome_Seg have been predicted to play a role in chromosome segregation during meiosis.[3]
# Gene
## Overview
The FAM214A gene is located on the negative DNA strand (see Sense (molecular biology)) of chromosome 15 between position 52,873,514 and 53,002,014; thus making the gene 97,303 base pairs (bp) long.[1][4][5] FAM214A has been previously labeled with two other aliases, known as KIAA1370 and FLJ10980.[1] The FAM214A gene is predicted to contain 12 exons which comprise the final 4231 bp mRNA transcript after transcription has occurred.[6] It is this mRNA product that is then translated into the final FAM214A protein with the help of the promoter sequence and transcription factors. The promoter for the FAM214A mRNA sequence was predicted and analyzed by the El Dorado program on Genomatix.[7] This promoter is 601 base pairs long and spans a portion of the 5' UTR.[7]
## Gene expression
FAM214A is considered to be ubiquitously expressed (or very nearly so) in low levels according to a number of sources such as BioGPS and the Expression Atlas.[8][9][10] As can be seen in the BioGPS image below, there is a significantly higher expression level in immune-related cells and tissues, thus suggesting an immune role; however, there has been no specific in situ evidence to support this claim. Expression data has been collected from a number of studies performed on a large range of genes, therefore, some of the data is contradictory in nature.
# Protein
## Overview
The function of the FAM214A protein in humans is still unknown; however, there are three functional term associations including "biological process," "cellular component," and molecular function," that describe the function of this protein on The Gene Ontology which predict implications of its primary function in vivo.[11][12] The protein product of FAM214A consists of 1076 amino acids (aa), has been predicted to have a molecular mass of 121,700 Daltons, and has an isoelectric point around pH 7.7.[2][13][14] This protein is predicted to remain in the nucleus after transcription based upon its lack of signal peptide sequence and the predictions of the program PSORTII.[15] Due to alternative splicing, two other isoforms (Q32MH5-2 and Q32MH5-3) have been observed. They differ slightly from the primary product.[16] Isoform 2 has four different amino acids from bases 960-960 and is missing the end of the sequence from bases 964-1076.[16] Isoform 3 has seven extra amino acids added to the beginning of the sequence after the methionine.[16]
After being translated, the FAM214A protein is predicted to remain in the nucleus by more than one type of subprogram on PSORT II.[15] This protein has a pat4 signal, one of the two "classical" nuclear localization signals (NLSs), starting at residue 709.[17] Although it does not have the second "classical" NLS, pat7, nor the "non-classical" bipartite NLS it is still predicted to be targeted for the nucleus by the NCNN score.[17][18] This score predicts whether the protein is targeted for the nucleus or the cytoplasm based upon the amino acid sequence.[17][18] For the FAM214A protein, the NCNN score predicted nuclear localization with 94.1% certainty.[17][18] Based upon this information, PSORT generates an overall prediction of the protein's subcellular localization. For FAM214A, the predicted values were 69.6% for the nucleus as compared to 13.0% for the mitochondria, 8.7% for the cytoplasm, and 4.3% for the secretory vesicles and endoplasmic reticulum.[15]
## Post-translational modifications
This protein most likely does not undergo a significant number of post-translational modifications due to the lack of signal peptide sequence predicted by NetNGlyc and NetOGlyc on the ExPASy web server.[20][21] This is because much of the intracellular machinery performing post-translational modifications requires the protein to move through organelles such as the endoplasmic reticulum and Golgi apparatus. Without a signal peptide sequence, the protein generally does not leave the nucleus, which was predicted by PSORT II as described above.[15]
A SAPS analysis of this protein was performed against the swp23s.q database, which indicated the presence of an abnormally large number of serine amino acids and an abnormally small number of alanine amino acids in this protein.[13] According to a review article by Fayard et al., phosphoinositide-dependent kinase 2 (PDK2) is a serine/threonine kinase that is important for regulating cell cycle. Because the FAM214A protein has a larger number of serine groups than is considered normal, there is the possibility that PDK2 has an important effect on this protein.[22] In order to determine whether the excessive number of serines were actually predicted to be phosphorylated, the protein sequence was run through the program NetPhos from the ExPASy webserver.[19] This program predicted the phosphorylation of 69 serines, 14 threonines, and 9 tyrosines.[19] According to the SAPS analysis from above, there are a total or 134 serines, thus indicating that approximately half are predicted to be phosphorylated in vivo. A diagram of the phosphorylation predictions is shown to the right.
One other type of post-translational modification was predicted for the FAM214A protein by the program NetCorona on ExPASy.[23] The program predicted a single cleavage site between position 214 and 215 in the FAM214A protein sequence after translation.[23]
## Protein interactions
There are number of transcription factor binding sites predicted for the FAM214A promoter sequence.[7] A few of the ones with the highest predicted confidence are provided in the table below.[7]
Possible Transcription Factors Predicted to Bind to the FAM214A Promoter Sequence
The only protein predicted according STRING to interact with the FAM214A protein is called MFSD6L. This protein belongs to the major facilitator superfamily is predicted to be a transmembrane protein. Like FAM214A, the function of this protein has not yet been characterized through experimentation or research.[24][25] Because this MFSD6L protein is the only FAM214A protein interaction predicted with any certainty, the sequence for it was run through the PSORT II program. The data from the NLS subprogram predicted the presence of a single pat4 and two pat7 NLS sequences, thus indicating possible nuclear localization.[15][17] The NCNN score, on the other hand, predicted cytoplasmic localiztion with 94.1% certainty, thus leaving the overall PSORT II score at 39.1% plasma membrane, 39.1% endoplasmic reticulum, 4.3% vacuolar, 4.3% vesicles of secretory system, 4.3% Golgi, 4.3% mitochondrial, and 4.3% nuclear.[17][18] This is contradictory as there are three total nuclear localization signals, but this may be due to the fact that the significant transmembrane nature of the MFSD6L protein may be causing issues with these predictions.[17]
## Secondary and tertiary structure
The secondary structure of the FAM214A protein consists of a number of alpha helices and beta sheets as predicted by Biology Workbench and Protein Homology/analogY Recognition Engine (PHYRE).[26][27] The PHYRE program predicts that 66 percent of the FAM214A secondary structure is disordered and therefore unable to be analyzed and converted into a tertiary structure prediction.[26] It was; however, able to predict approximately 10 percent of the protein's structure with 95 percent significance.[26] The diagram for this is shown to the left.[26]
# Conservation
## Paralog
A single paralogous gene has been found on chromosome 9 in Homo sapiens and is named FAM214B (family with sequence similarity, B).[28] FAM214B, although considered a paralog, has a significantly different protein sequence from that of FAM214A. When the two were compared against each other on NCBI’s BLAST, the only significant similarity observed was within the last 200 amino acids (where the DUF4210 and Chromosome_Seg domains are located).[29] Although the similarity between FAM214A and B is low, these two proteins are in the same protein family and contain the same two conserved domains.[3][30]
## Orthologs
The FAM214A protein has a significant number of orthologs across a large number of taxonomic groups including Mammalia, Aves, Reptilia, Amphibia, Actinopterygii, Echinoidea, Insecta, Trematoda, Crustacea, Tricoplacia, Anthozoa, and Eurotiomycetes.[31] This indicates that the FAM214A protein is well conserved within Eukaryotes but does not appear to be conserved in Bacteria or Archaea. In all orthologs, the most-conserved region was near the end of the protein where the conserved domains are (see below). Orthologs for the human FAM214A protein were found as far back as Tuber melanosporum, Talaromyces stipitatus, and Aspergillus nidulans, which all diverged approximately 1215 million years ago.
Orthologs for the FAM214A Protein
## Phylogeny
An unrooted phylogenetic tree of 20 orthologs was generated by the CLUSTALW program on Biology Workbench to demonstrate the evolutionary relationship between FAM214A and its orthologs.[27]
## Conserved domains
Within the FAM214A protein, there are three well-conserved regions. These include a well-conserved region near the n-terminus of the protein and two conserved domains including the Domain of Unknown Function 4210 (DUF4210) and a Chromosome_Seg domain near the c-terminus.[3] A schematic diagram of these three regions is shown below. The well-conserved region near the n-terminus of the protein is not predicted to contain any known domains or motifs; however, the cleavage site predicted by NetCorona above is located within this region and it is well-conserved in a majority of the proteins orthologous to FAM214A.[23] The two conserved domains located at the end of this protein are the most important portion of the peptide based upon evolutionary history. All organisms in the Ortholog table above except the platypus (which is missing the Chromosome_Seg domain) contain both of these conserved domains within their protein sequence.[3] | https://www.wikidoc.org/index.php/FAM214A | |
a0db12c7fa32f90077c1143e1fdf1a501a52328c | wikidoc | FAM221A | FAM221A
Family with sequence similarity 221 member A is a protein in humans that is encoded by the FAM221A gene. FAM221A is a gene that is not yet well understood by the scientific community. However, it appears that this gene may have a role in Parkinson's Disease and Prostate Cancer.
# Gene
## Location and Aliases
FAM221A is located on Chromosome 7. Its exact location is 7p15.3. It has one alias, which is C7orf46.
## Expression
FAM221A has higher levels of expression in the liver, brain, fetal brain, thyroid and colon, but FAM221A has the highest level of expression in the spinal cord, pancreas and retina.
The promoter region of FAM221A is 1222 base pairs long. This was found using ElDorado at Genomatix.
# Protein
## Protein Analysis
The molecular weight of FAM221A is 33.1 kDa, and the isoelectric point is 6.01. Relative to other proteins in humans, FAM221A has a lower level of Asparagine.
## Post-Translational Modifications
Post-translational modifications of FAM221A include phosphorylation sites, glycosylation sites and sulfation sites. These have been conserved in mammals other than Homo sapiens, including the macaque, whale, finch and sometimes alligator. These sites were predicted using NetPhos 3.1, YinOYang 1.2 and The Sulfinator.
## Secondary Structure
Key structures predicted in FAM221A are random coils and alpha helices, with 71% of the protein being random coils and 21% being helices. Extended strands were also found with 7% of the protein being these. Secondary structure was predicted using RaptorX, and a diagram of the predicted secondary structure is included below.
# Homology/evolution
## Paralogs
There exists one paralog for FAM221A: FAM221B. This diverged from FAM221A approximately 1781 million years ago.
## Orthologs
Orthologs have been found in mammals, birds, reptiles and fish. FAM221A has also been conserved in invertebrates, but the similarity levels decrease at a faster rate. Orthologs were discovered using BLAST and BLAT. While these are not the only orthologs that exist for FAM221A, a table of 20 orthologs is provided below. The ortholog with no accession number was created using BLAT.
## Divergence of FAM221A
To understand the times when FAM221A diverged from different species, a graph was created. This compares the evolutionary history of FAM221A to Fibrinogen, which evolves quickly, and Cytochrome C, which evolves slowly. As seen in the graph, FAM221A diverges from other species at a moderate pace.
# Clinical significance
FAM221A has a relatively high amount of expression in the brain and has been seen to have an association with neurodegenerative disorders like Parkinson's Disease and Alzheimer's Disease. FAM221A has also been seen to have a higher level of expression in those who have prostate cancer versus healthy individuals. Furthermore, FAM221A has also been expressed in those with colorectal tumors.
# Interacting Proteins
Three interacting proteins were found, which are SNX2, SNX5 and SNX6.
SNX2 and SNX6 share the same function, which is being involved in the stages of intracellular trafficking. SNX5 facilitates cargo retrieval from endosomes to the trans-golgi network. | FAM221A
Family with sequence similarity 221 member A is a protein in humans that is encoded by the FAM221A gene. FAM221A is a gene that is not yet well understood by the scientific community. However, it appears that this gene may have a role in Parkinson's Disease and Prostate Cancer.
# Gene
## Location and Aliases
FAM221A is located on Chromosome 7. Its exact location is 7p15.3.[1] It has one alias, which is C7orf46.[2]
## Expression
FAM221A has higher levels of expression in the liver, brain, fetal brain, thyroid and colon, but FAM221A has the highest level of expression in the spinal cord, pancreas and retina.[3]
The promoter region of FAM221A is 1222 base pairs long. This was found using ElDorado at Genomatix.[4]
# Protein
## Protein Analysis
The molecular weight of FAM221A is 33.1 kDa,[5] and the isoelectric point is 6.01.[6] Relative to other proteins in humans, FAM221A has a lower level of Asparagine.[5]
## Post-Translational Modifications
Post-translational modifications of FAM221A include phosphorylation sites, glycosylation sites and sulfation sites. These have been conserved in mammals other than Homo sapiens, including the macaque, whale, finch and sometimes alligator. These sites were predicted using NetPhos 3.1,[7] YinOYang 1.2[8] and The Sulfinator.[9]
## Secondary Structure
Key structures predicted in FAM221A are random coils and alpha helices, with 71% of the protein being random coils and 21% being helices. Extended strands were also found with 7% of the protein being these. Secondary structure was predicted using RaptorX,[10] and a diagram of the predicted secondary structure is included below.
# Homology/evolution
## Paralogs
There exists one paralog for FAM221A: FAM221B. This diverged from FAM221A approximately 1781 million years ago.
## Orthologs
Orthologs have been found in mammals, birds, reptiles and fish. FAM221A has also been conserved in invertebrates, but the similarity levels decrease at a faster rate. Orthologs were discovered using BLAST [11] and BLAT.[12] While these are not the only orthologs that exist for FAM221A, a table of 20 orthologs is provided below. The ortholog with no accession number was created using BLAT.
## Divergence of FAM221A
To understand the times when FAM221A diverged from different species, a graph was created. This compares the evolutionary history of FAM221A to Fibrinogen, which evolves quickly, and Cytochrome C, which evolves slowly. As seen in the graph, FAM221A diverges from other species at a moderate pace.
# Clinical significance
FAM221A has a relatively high amount of expression in the brain[13] and has been seen to have an association with neurodegenerative disorders like Parkinson's Disease[13] and Alzheimer's Disease.[14] FAM221A has also been seen to have a higher level of expression in those who have prostate cancer versus healthy individuals.[15] Furthermore, FAM221A has also been expressed in those with colorectal tumors.[16]
# Interacting Proteins
Three interacting proteins were found, which are SNX2, SNX5 and SNX6.
SNX2 and SNX6 share the same function, which is being involved in the stages of intracellular trafficking. SNX5 facilitates cargo retrieval from endosomes to the trans-golgi network. | https://www.wikidoc.org/index.php/FAM221A | |
ba7bab4987388973a3a1bad312d325facc5ac6e4 | wikidoc | FAM227a | FAM227a
FAM227A is a protein that in humans is encoded by FAM227A gene. Current studies have determined the location of this gene to be in the nuclear region of the cell. FAM227A is most highly expressed in the tissues of the fallopian tube, testis, and pituitary gland. FAM227A is present in species of mammals, birds and reptiles, and gene alignment sequences have shown that FAM227A is a rapidly evolving gene.
# Gene
FAM227A is found on chromosome 22 at the location 22q13.1. It is flanked by the gene LOC105373031 on the left and CBY1 on the right. The gene is 78,510 base pairs long with 21 exons. There are currently no aliases for FAM227A.
# mRNA
There are two isoforms of FAM227A. The first isoform, NM_001013647.1, has a shorter transcript but a longer isoform. It is 2,948 base pairs long, and includes the first 17 exons. The second isoform, NM_001291030.1, is 10,362 base pairs long. It starts translation at a different start codon than variant 1 by utilizing an alternate splice site. The 5’ region is relatively short but the 3’ region is very long.
# Protein
The primary sequence for FAM227A is isoform 1 with accession number: NP_001013669.1. It is 570 amino acids long. There are 9 isoforms. The molecular weight is 66kD, and the isoelectric point is 9.6. Compared to other proteins in humans, FAM227A has less abundant glycine and more abundant hydrophobic amino acids and positively charges amino acids. The protein is predicted to be in the nuclear region of the cell. Three nuclear signals include HKKK at 129(pat 4), KKK at 130(pat4), and PKKTKIK at 410(pat7). An FWWh region, where h signifies hydrophobic, runs from amino acids 135-296 in Homo sapiens. Most eukaryotic proteins contain this sequence. The function of this region is still unknown. Motifs in FAM227A include KRK, SGK, and RRE.
## Secondary Structure
The secondary structure is predicted to be made up of alpha helices mainly. but also beta pleated sheets.
## Post-Translational Modification
Phosphorylation is the only predicted post-translational modification. There are three experimentally determined phosphorylation sites at Y343, S348, and S349.
## Expression
FAM227A is experimentally determined to be highly expressed in the testis, epididymis, pituitary gland, and the fallopian tubes. This protein is not predicted to be ubiquitous as the rate of expression varies across tissue types.
## Function
Currently, the function of FAM227A has not been characterized.
## Interacting Proteins
Currently, there are no predicted proteins that interact with FAM227A
## Subcellular Localization
FAM227A is predicted to be located in the nuclear region of the cell. This prediction is consistent across species.
# Homology
Paralogs: FAM227B
Orthologs: FAM227A is present mainly in mammals but also in species of reptiles and birds. The most distantly related ortholog is Xenopus tropicalis, the Western Clawed Frog. Based on the years of divergence for FAM227A, the gene evolved very rapidly.
# Clinical Significance
In 2016, a study performed an association analysis on chromosome 22 at 31203 markers in order to determine if high blood pressure and smoking were correlated. Chromosome 22 was chosen based on the results of the data collected from three clinical visits at the Framingham Heart Study. In 2013, researchers investigated 3 clusters of SNP’s thought to be linked to prostate cancer in Arab populations. The study found that the deletion region on chromosome 22q13, where FAM227A is located, can also be linked to breast and colorectal cancer in humans in addition to prostate cancer3. Another study suggests the location of FAM227A may be linked to a central regulator, SOX10, which is involved in the maturation of neural crest derivatives. Gene deletion of FAM227A was linked to lung abnormality, atrial septum defect, small size for gestational age, and sensorineural hearing loss in this study. | FAM227a
FAM227A is a protein that in humans is encoded by FAM227A gene. Current studies have determined the location of this gene to be in the nuclear region of the cell.[1] FAM227A is most highly expressed in the tissues of the fallopian tube, testis, and pituitary gland. FAM227A is present in species of mammals, birds and reptiles, and gene alignment sequences have shown that FAM227A is a rapidly evolving gene.[2]
# Gene
FAM227A is found on chromosome 22 at the location 22q13.1. It is flanked by the gene LOC105373031 on the left and CBY1 on the right. The gene is 78,510 base pairs long with 21 exons. There are currently no aliases for FAM227A.[3]
# mRNA
There are two isoforms of FAM227A. The first isoform, NM_001013647.1, has a shorter transcript but a longer isoform. It is 2,948 base pairs long, and includes the first 17 exons. The second isoform, NM_001291030.1, is 10,362 base pairs long. It starts translation at a different start codon than variant 1 by utilizing an alternate splice site. The 5’ region is relatively short but the 3’ region is very long.[4]
# Protein
The primary sequence for FAM227A is isoform 1 with accession number: NP_001013669.1. It is 570 amino acids long. There are 9 isoforms. The molecular weight is 66kD,[4] and the isoelectric point is 9.6.[6] Compared to other proteins in humans, FAM227A has less abundant glycine and more abundant hydrophobic amino acids and positively charges amino acids.[7] The protein is predicted to be in the nuclear region of the cell. Three nuclear signals include HKKK at 129(pat 4), KKK at 130(pat4), and PKKTKIK at 410(pat7).[1] An FWWh region, where h signifies hydrophobic, runs from amino acids 135-296 in Homo sapiens. Most eukaryotic proteins contain this sequence. The function of this region is still unknown.[3] Motifs in FAM227A include KRK, SGK, and RRE.
## Secondary Structure
The secondary structure is predicted to be made up of alpha helices mainly. but also beta pleated sheets.[8]
## Post-Translational Modification
Phosphorylation is the only predicted post-translational modification. There are three experimentally determined phosphorylation sites at Y343, S348, and S349.[4]
## Expression
FAM227A is experimentally determined to be highly expressed in the testis, epididymis, pituitary gland, and the fallopian tubes. This protein is not predicted to be ubiquitous as the rate of expression varies across tissue types.[11]
## Function
Currently, the function of FAM227A has not been characterized.
## Interacting Proteins
Currently, there are no predicted proteins that interact with FAM227A
## Subcellular Localization
FAM227A is predicted to be located in the nuclear region of the cell. This prediction is consistent across species.[1]
# Homology
Paralogs: FAM227B
Orthologs: FAM227A is present mainly in mammals but also in species of reptiles and birds. The most distantly related ortholog is Xenopus tropicalis, the Western Clawed Frog. Based on the years of divergence for FAM227A, the gene evolved very rapidly.[2]
# Clinical Significance
In 2016, a study performed an association analysis on chromosome 22 at 31203 markers in order to determine if high blood pressure and smoking were correlated. Chromosome 22 was chosen based on the results of the data collected from three clinical visits at the Framingham Heart Study.[12] In 2013, researchers investigated 3 clusters of SNP’s thought to be linked to prostate cancer in Arab populations. The study found that the deletion region on chromosome 22q13, where FAM227A is located, can also be linked to breast and colorectal cancer in humans in addition to prostate cancer3.[13] Another study suggests the location of FAM227A may be linked to a central regulator, SOX10, which is involved in the maturation of neural crest derivatives. Gene deletion of FAM227A was linked to lung abnormality, atrial septum defect, small size for gestational age, and sensorineural hearing loss in this study.[14] | https://www.wikidoc.org/index.php/FAM227a | |
0df2edd7998240863e8c980deed0cfadcf0be016 | wikidoc | FAM231B | FAM231B
FAM231B, or family with sequence similarity 231B, is a protein found in humans and is encoded by FAM231B gene. Orthologs of FAM231B are only found back to primates.
# Gene
FAM231B is found on human Chromosome 1 on locus 1p36.13 running in the positive direction, surrounded by RNU1-6P upstream and transfer RNA-Gly 4-1 downstream. There are no aliases of FAM231B.
Its mRNA sequence is 1312 base pairs long, with the coding sequence in region 343 through 852, and there is only one exon.
# Protein
The protein is 169 amino acids long. The molecular weight of the unprocessed protein is 18.2 kDa and the processed protein is 18.3 kDa. The isoelectric point of the protein is 7.76 and a mixed charged cluster was found from amino acid 66 to 125. Other features of the protein include a positive charge run and a negative charge run, both spanning 4 amino acids.
The predicted secondary structure of the protein consists of many coils, 3 β-sheets and 5 α-helixes. Potential post-translational modifications of the protein include myristoylation and sumoylation.The mature protein is predicted to be transported to the nucleus.
# Expression in Tissues
FAM231B is highly regulated in brain tissue and the spinal cord. From GeoProfiles, other tissues where expression is regulated are visceral fat, adipose, thyroid, breast, coronary artery, pancreas, colon, vaginal epithelium, smooth muscle, and fallopian tube epithelium.
# Regulation of Expression
FAM231B contains a Kozak consensus sequence surrounding the start codon nucleotides. The primary promoter region for the human FAM231B gene is 1443 base pairs long.
Predicted regulation in the secondary structure are two stem loops in the 5' UTR and two more in the 3' UTR.
# Function
The function of the protein is not yet well understood in the scientific community. The protein contains domain of unknown function (DUF) 4741, which is part of the FAM231 family.
# Homology & Evolution
There are three human paralogs: FAM231A, FAM231C, and FAM231D and a comparison of the protein percent identity and similarity are found in the table below. There are three strict orthologs of FAM231B: in humans, the Pan troglodytes (Common chimpanzee), and the Papio anubis (Olive baboon). No other orthologs are found beyond primates.
The evolutionary rate of FAM231B was compared to Fibrinogen and Cytochrome C. FAM231B is predicted to have evolved faster than both of the proteins compared.
## Table of FAM231B Paralogs
## Table of FAM231B Orthologs | FAM231B
FAM231B, or family with sequence similarity 231B, is a protein found in humans and is encoded by FAM231B gene.[1] Orthologs of FAM231B are only found back to primates.[2]
# Gene
FAM231B is found on human Chromosome 1 on locus 1p36.13 running in the positive direction, surrounded by RNU1-6P upstream and transfer RNA-Gly 4-1 downstream.[3][4] There are no aliases of FAM231B.[5]
Its mRNA sequence is 1312 base pairs long, with the coding sequence in region 343 through 852, and there is only one exon.[6]
# Protein
The protein is 169 amino acids long.[7] The molecular weight of the unprocessed protein is 18.2 kDa and the processed protein is 18.3 kDa.[8] The isoelectric point of the protein is 7.76 and a mixed charged cluster was found from amino acid 66 to 125.[9] Other features of the protein include a positive charge run and a negative charge run, both spanning 4 amino acids.[10]
The predicted secondary structure of the protein consists of many coils, 3 β-sheets and 5 α-helixes.[11] Potential post-translational modifications of the protein include myristoylation and sumoylation.[12][13]The mature protein is predicted to be transported to the nucleus.[14]
# Expression in Tissues
FAM231B is highly regulated in brain tissue and the spinal cord.[15] From GeoProfiles, other tissues where expression is regulated are visceral fat, adipose, thyroid, breast, coronary artery, pancreas, colon, vaginal epithelium, smooth muscle, and fallopian tube epithelium.[16]
# Regulation of Expression
FAM231B contains a Kozak consensus sequence surrounding the start codon nucleotides. The primary promoter region for the human FAM231B gene is 1443 base pairs long.[17]
Predicted regulation in the secondary structure are two stem loops in the 5' UTR and two more in the 3' UTR.[18]
# Function
The function of the protein is not yet well understood in the scientific community. The protein contains domain of unknown function (DUF) 4741, which is part of the FAM231 family.[19]
# Homology & Evolution
There are three human paralogs: FAM231A, FAM231C, and FAM231D and a comparison of the protein percent identity and similarity are found in the table below. There are three strict orthologs of FAM231B: in humans, the Pan troglodytes (Common chimpanzee), and the Papio anubis (Olive baboon). No other orthologs are found beyond primates.[20]
The evolutionary rate of FAM231B was compared to Fibrinogen and Cytochrome C. FAM231B is predicted to have evolved faster than both of the proteins compared.
## Table of FAM231B Paralogs
## Table of FAM231B Orthologs | https://www.wikidoc.org/index.php/FAM231B | |
c5bbdb67af8111a5dcf031e99a4a639d98b25aad | wikidoc | FAM71E1 | FAM71E1
FAM71E1, also known as Family With Sequence Similarity 71 Member E1, is a protein that in humans is encoded by the FAM71E1 gene. It is thought to be ubiquitously expressed at low levels throughout the body, and it is conserved in vertebrates, particularly mammals and some reptiles. The protein is localized to the nucleus and can be exported to the cytoplasm.
# Gene
## Location
The gene is located on the minus strand at 19q13.33 and spans from 50,466,643 to 50,476,753. It is 10,070 bp long.
## Gene Neighbohood
In humans, the gene is flanked by the following genes:
- SPIB: putative oncogene that is active in hematopoietic cells
- MYBPC2: encodes a structural protein and is actively expressed in striated muscle cells
- EMC10: encodes a protein of unknown function
- JOSD2: encodes a protein involved in de-ubiquitination
## Promoter
The promoter of FAM71E1 is located on the minus strand from 50,476,094 to 50,477,946 . It is 1,853 bp long.
## Expression
The gene seems to be ubiquitously expressed at low levels throughout the body but has prominent expression in the adult human testis, followed by lower expression levels in the sperm, oocyte, and brain. Age does not have an effect on its expression in the skeletal muscle of males or females. Its expression is elevated prior to the differentiation of embryonic stem cells into pancreatic islet-like cells.
# Transcript
## Isoforms
The FAM71E1 gene produces two isoforms from alternative splicing. Isoform 1 is 1281 bp long, and isoform 2 is slightly shorter at 1233 bp long. Both transcript variants have 5 exons, 4 of which are coding exons. The third intron for the isoform 2 transcript is longer than the one found in isoform 1.
## Regulation
The FAM71E1 transcript is regulated by micro-RNAs, such as miR-149, miR-7, miR-125b, miR-125a-5p, miR192-5p, and miR-215.
# Protein
## Properties
The protein from isoform 1 is 247 amino acids long with a molecular weight of 27.6 kDa. It has a charge of 5.0 and an isoelectric point of 8.9. It has a domain of unknown function (DUF3699), which is conserved in eukaryotes and has no known pairwise interactions with other domains. The structure of the protein has 3 alpha helices and 5 beta strands.
## Localization
The protein is predicted to localize to the nucleus and thought to be mainly associated with the nucleoli fibrillar center. It can also be exported to the cytoplasm.
# Homologs
## Paralogs
The FAM71E1 gene is fast evolving. It has the following 8 paralogs: FAM71A, FAM71B, FAM71C, FAM71D, FAM71E2, FAM71F1, FAM71F2, and AC020922.1. FAM71D, FAM71E2 and AC0209221.1 are found in Amniotes and their last common ancestor with FAM71E1 was likely in the ancestor of the Sauria taxon, which includes reptiles and birds. The remaining paralogs are found in mammals and are expressed in organisms from the evolutionary descendants of the lobe-finned fish (Sarcopterygii). Their last common ancestor with FAM71E1 was Coelacanth (Latimeria chalumnae).
## Orthologs
Orthologs of FAM71E1 can be found only in vertebrates, primarily in placental mammals in the Boreoeutheria group and occasionally in a few reptilian species. Reptiles and marsupials are included in the distant homologs, while orthologs in placental animals such as rodents and primates are more closely related to FAM71E1. The gene history contains 27 duplication events and 1 splitting event.
# Clinical Significance
## Mutations
There are no disease-causing mutations associated with this gene, and it is tolerant towards loss-of-function variants.
## Disease Associations
FAM71E1 has reduced expression in Type 2 diabetes patients and is likely not involved in the disease's pathophysiology. Its expression is also altered in Parkinson's disease and several cancers, such as non-triple negative ductal carcinoma in situ, breast cancer, pancreatic adenocarcinoma, and colorectal carcinoma. It is a gene of interest in predicting susceptibility to pneumonia. | FAM71E1
FAM71E1, also known as Family With Sequence Similarity 71 Member E1, is a protein that in humans is encoded by the FAM71E1 gene.[1][2] It is thought to be ubiquitously expressed at low levels throughout the body, and it is conserved in vertebrates, particularly mammals and some reptiles. The protein is localized to the nucleus and can be exported to the cytoplasm.
# Gene
## Location
The gene is located on the minus strand at 19q13.33 and spans from 50,466,643 to 50,476,753. It is 10,070 bp long.[1][2]
## Gene Neighbohood
In humans, the gene is flanked by the following genes:[1][2]
- SPIB: putative oncogene that is active in hematopoietic cells [3]
- MYBPC2: encodes a structural protein and is actively expressed in striated muscle cells [4]
- EMC10: encodes a protein of unknown function [5]
- JOSD2: encodes a protein involved in de-ubiquitination [6]
## Promoter
The promoter of FAM71E1 is located on the minus strand from 50,476,094 to 50,477,946 . It is 1,853 bp long.[7]
## Expression
The gene seems to be ubiquitously expressed at low levels throughout the body [8][9][10] but has prominent expression in the adult human testis,[11] followed by lower expression levels in the sperm, oocyte, and brain.[12][13][14][15][16] Age does not have an effect on its expression in the skeletal muscle of males or females.[17] Its expression is elevated prior to the differentiation of embryonic stem cells into pancreatic islet-like cells.[18]
# Transcript
## Isoforms
The FAM71E1 gene produces two isoforms from alternative splicing. Isoform 1 is 1281 bp long, and isoform 2 is slightly shorter at 1233 bp long.[19] Both transcript variants have 5 exons, 4 of which are coding exons. The third intron for the isoform 2 transcript is longer than the one found in isoform 1.[20]
## Regulation
The FAM71E1 transcript is regulated by micro-RNAs, such as miR-149, miR-7, miR-125b, miR-125a-5p, miR192-5p, and miR-215.[21]
# Protein
## Properties
The protein from isoform 1 is 247 amino acids long with a molecular weight of 27.6 kDa. It has a charge of 5.0 and an isoelectric point of 8.9.[20] It has a domain of unknown function (DUF3699), which is conserved in eukaryotes and has no known pairwise interactions with other domains.[22] The structure of the protein has 3 alpha helices and 5 beta strands.
## Localization
The protein is predicted to localize to the nucleus and thought to be mainly associated with the nucleoli fibrillar center.[23] It can also be exported to the cytoplasm.[10]
# Homologs
## Paralogs
The FAM71E1 gene is fast evolving. It has the following 8 paralogs: FAM71A, FAM71B, FAM71C, FAM71D, FAM71E2, FAM71F1, FAM71F2, and AC020922.1. FAM71D, FAM71E2 and AC0209221.1 are found in Amniotes and their last common ancestor with FAM71E1 was likely in the ancestor of the Sauria taxon, which includes reptiles and birds. The remaining paralogs are found in mammals and are expressed in organisms from the evolutionary descendants of the lobe-finned fish (Sarcopterygii). Their last common ancestor with FAM71E1 was Coelacanth (Latimeria chalumnae).[25]
## Orthologs
Orthologs of FAM71E1 can be found only in vertebrates, primarily in placental mammals in the Boreoeutheria group and occasionally in a few reptilian species. Reptiles and marsupials are included in the distant homologs, while orthologs in placental animals such as rodents and primates are more closely related to FAM71E1. The gene history contains 27 duplication events and 1 splitting event.[25]
# Clinical Significance
## Mutations
There are no disease-causing mutations associated with this gene,[27] and it is tolerant towards loss-of-function variants.[28]
## Disease Associations
FAM71E1 has reduced expression in Type 2 diabetes patients and is likely not involved in the disease's pathophysiology.[29] Its expression is also altered in Parkinson's disease[30] and several cancers, such as non-triple negative ductal carcinoma in situ,[31] breast cancer,[32] pancreatic adenocarcinoma, and colorectal carcinoma.[30] It is a gene of interest in predicting susceptibility to pneumonia.[33] | https://www.wikidoc.org/index.php/FAM71E1 | |
33d8b35b6854d5ef973304a0f5a9034d1b04daea | wikidoc | FAM71F2 | FAM71F2
FAM71F2 or Family with Sequence Similarity 71 member F2 is a protein that in humans is encoded by the Family with Sequence Similarity 71 member F2 gene. This gene is highly active in the reproductive tissues, specifically the testis, and may serve as a potential biomarker for determining metastatic testicular cancer.
# Gene
## Location
FAM71F2 gene is located on chromosome 7 in humans (7q32.1), starting at 128,671,636 and ending at 128,702,262 on the positive strand. The gene paralog FAM71F1 and the gene LINC01000 directly neighbor FAM71F2 on chromosome 7.
## Size of gene
The gene spans 30,627 base pairs and codes for 12 exons.
## Common aliases
FAM71F2 is also referred to as family with sequence similarity 137 member B, FAM137B.
# mRNA
FAM71F2 has 14 transcript variants. Isoform a is the longest of the mRNA transcripts and spans 5,775 base pairs that translates into a 309 amino acids sequence. It codes for 5 exons. Other alternative splice isoforms are labelled in the diagram in Figure 2.
At the first splice site, Isoform b, found in most reptiles having FAM71F2 protein, deletes the following nine amino acids and picks up at the valine amino acid at location 61 in humans. Isoform c uses an alternative downstream start site to Isoform a and adds another exon between the first and second exons of Isoform a.
## General properties
The molecular weight of FAM71F2 is 34.5 kilo Daltons. The isoelectric point is 6.15.
## Domains and motifs
FAM71F2 protein contains only one domain, named domain of unknown function, DUF3699. This domain is located from amino acids 114-185 on the human FAM71F2 protein. This domain family is found only in eukaryotes and approximately 71 amino acids in length. There is also a potential R-2 mitochondrial pre-sequence cleavage site that would signal the protein to the mitochondria. These sites are labelled in Figure 4 below.
## Secondary structure
The secondary structure of FAM71F2 contains alpha helices and beta sheets. These structures are identified in the generated image of the FAM71F2 protein in Figure 3. Highly conserved amino acid residues, such as the Val61-Thr62-Lys63 sequence where the reptiles and isoform b pick up in the second exon, are labelled on this figure as well.
## Post-translational modifications
FAM71F2 has seven highly conserved phosphorylated sites. There is one acetylation site and one N-glycosylation site, playing a role in stabilizing the protein.
## Sub-cellular localization
FAM71F2 protein stays in the cytoplasm of cells, but may have localization in the nucleus and mitochondria.
# Expression
## Tissue expression pattern
FAM71F2 is highly expressed in reproductive structures, such as the testis, epididymis, uterus and ovaries. There is some expression in the brain and connective tissue as well. As development stages progress, the number of gene transcripts increases and are at highest expression levels in adults. In the mouse, during spermatogenesis and development of the testis, gene transcript levels of FAM71F2 increase dramatically.
## Cellular expression
FAM71F2 protein expression has been detected in the cytoplasm of Leydig cells and in epididymis cells of the male testis and is also detected in the cytoplasm in ovarian follicles.
## Expression level
FAM71F2 is moderately expressed in comparison to other proteins in the human, with an average protein expression level of 8.47 part per million.
# Clinical significance
FAM71F2 is repressed in males with non-obstructive azoospermia and teratozoospermia, or abnormalities in sperm morphology and quantity. These diseases lead to fertility issues. In addition, FAM71F2 gene expression is up-regulated with Dopamine receptor D1 expression in testicular cancer patients, and may be an important biomarker for metastatic forms of this cancer.
# Homology
FAM71F2 has 91 orthologs in other animal species. Its evolutionary history goes as far back as the reptiles, and its most distant relative is the homolog in the west Indian Ocean coelacanth. The time of divergence between eight orthologs from the human FAM71F2 is shown in Figure 5. It is not found in birds or in Gallus gallus (chicken). FAM71F2 has six paralogs in humans: FAM71A, FAM71B, FAM71C, FAM71D, FAM71E1, and FAM71F1. | FAM71F2
FAM71F2 or Family with Sequence Similarity 71 member F2 is a protein that in humans is encoded by the Family with Sequence Similarity 71 member F2 gene. This gene is highly active in the reproductive tissues, specifically the testis, and may serve as a potential biomarker for determining metastatic testicular cancer.
# Gene
## Location
FAM71F2 gene is located on chromosome 7 in humans (7q32.1),[1][2] starting at 128,671,636 and ending at 128,702,262 on the positive strand.[2] The gene paralog FAM71F1 and the gene LINC01000 directly neighbor FAM71F2 on chromosome 7.
## Size of gene
The gene spans 30,627 base pairs[2] and codes for 12 exons.[1]
## Common aliases
FAM71F2 is also referred to as family with sequence similarity 137 member B, FAM137B.[2]
# mRNA
FAM71F2 has 14 transcript variants.[1] Isoform a is the longest of the mRNA transcripts and spans 5,775 base pairs that translates into a 309 amino acids sequence.[1] It codes for 5 exons.[1] Other alternative splice isoforms are labelled in the diagram in Figure 2.
At the first splice site, Isoform b, found in most reptiles having FAM71F2 protein, deletes the following nine amino acids and picks up at the valine amino acid at location 61 in humans. Isoform c uses an alternative downstream start site to Isoform a and adds another exon between the first and second exons of Isoform a.
## General properties
The molecular weight of FAM71F2 is 34.5 kilo Daltons.[3] The isoelectric point is 6.15.[4]
## Domains and motifs
FAM71F2 protein contains only one domain, named domain of unknown function, DUF3699.[1][2] This domain is located from amino acids 114-185 on the human FAM71F2 protein.[1] This domain family is found only in eukaryotes and approximately 71 amino acids in length.[1] There is also a potential R-2 mitochondrial pre-sequence cleavage site[5] that would signal the protein to the mitochondria. These sites are labelled in Figure 4 below.
## Secondary structure
The secondary structure of FAM71F2 contains alpha helices and beta sheets.[6][7] These structures are identified in the generated image of the FAM71F2 protein in Figure 3. Highly conserved amino acid residues, such as the Val61-Thr62-Lys63 sequence where the reptiles and isoform b pick up in the second exon, are labelled on this figure as well.
## Post-translational modifications
FAM71F2 has seven highly conserved phosphorylated sites. There is one acetylation site[9] and one N-glycosylation site,[10] playing a role in stabilizing the protein.
## Sub-cellular localization
FAM71F2 protein stays in the cytoplasm of cells,[5] but may have localization in the nucleus and mitochondria.[5]
# Expression
## Tissue expression pattern
FAM71F2 is highly expressed in reproductive structures, such as the testis, epididymis, uterus and ovaries.[1][12] There is some expression in the brain and connective tissue as well.[13] As development stages progress, the number of gene transcripts increases and are at highest expression levels in adults.[13] In the mouse, during spermatogenesis and development of the testis, gene transcript levels of FAM71F2 increase dramatically.[14]
## Cellular expression
FAM71F2 protein expression has been detected in the cytoplasm of Leydig cells and in epididymis cells of the male testis and is also detected in the cytoplasm in ovarian follicles.[12]
## Expression level
FAM71F2 is moderately expressed in comparison to other proteins in the human, with an average protein expression level of 8.47 part per million.[15]
# Clinical significance
FAM71F2 is repressed in males with non-obstructive azoospermia[16] and teratozoospermia,[17] or abnormalities in sperm morphology and quantity. These diseases lead to fertility issues. In addition, FAM71F2 gene expression is up-regulated with Dopamine receptor D1 expression in testicular cancer patients, and may be an important biomarker for metastatic forms of this cancer.[18][19][16]
# Homology
FAM71F2 has 91 orthologs in other animal species.[1] Its evolutionary history goes as far back as the reptiles, and its most distant relative is the homolog in the west Indian Ocean coelacanth.[20][21][22] The time of divergence between eight orthologs from the human FAM71F2 is shown in Figure 5. It is not found in birds or in Gallus gallus (chicken).[21][1] FAM71F2 has six paralogs in humans: FAM71A, FAM71B, FAM71C, FAM71D, FAM71E1, and FAM71F1.[1] | https://www.wikidoc.org/index.php/FAM71F2 | |
2009b0d9a16d8d2c4e4881a1b7672c3793cded7e | wikidoc | FASTKD1 | FASTKD1
FAST kinase domain-containing protein 1 is a protein that in humans is encoded by the FASTKD1 gene on chromosome 2. This protein is part of the FASTKD family, which is known for regulating the energy balance of mitochondria under stress. FASTKD1 is also an RNA-binding protein and has been associated with endometrial cancer.
# Structure
FASTKD1 shares structural characteristics of the FASTKD family, including an N-terminal mitochondrial targeting domain and three C-terminal domains: two FAST kinase-like domains (FAST_1 and FAST_2) and a RNA-binding domain (RAP). The mitochondrial targeting domain directs FASTKD1 to be imported into the mitochondria. Though the functions of the C-terminal domains are unknown, RAP possibly binds RNA during trans-splicing.
# Function
As a member of the FASTKD family, FASTKD1 localizes to the mitochondria to modulate their energy balance, especially under conditions of stress. Though ubiquitously expressed in all tissues, FASTKD1 appears more abundantly in skeletal muscle, heart muscle, and other tissues enriched in mitochondria. FASTKD1 has been validated as an RNA-binding protein.
# Clinical Significance
FASTKD1 is an important apoptotic constituent. During a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response. It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.
FASTKD1 has been identified as a potential molecular biomarker for endometrial cancer, a cancer of the female genital tract, most notably using uterine aspirates This finding represent the basis for the development of a highly sensitive and specific minimally invasive method for the screenings of endometrial cancer. Accordingly, gene expression screening on 52 carcinoma samples and series of real-time quantitative PCR validation on 19 paired carcinomas and normal tissue samples and on 50 carcinoma and non carcinoma uterine aspirates were performed to identify and validate potential biomarkers of endometrial cancer. Furthermore, another study designed a strategy to explore gene expression signatures associated with the survival in acute lymphoblastic leukemia (ALL), to search for aberrant gene activity, which consists of applying several filters to transcriptomic datasets from two pediatric ALL studies. Six genes whose expression in leukemic blasts was associated with prognosis were identified:three genes predicting poor prognosis (AK022211, FASTKD1 and STARD4) and three genes associated with a favorable outcome (CAMSAP1, PCGF6 and SH3RF3). Thus it appears that FASTKD1 may also play a role in ALL. | FASTKD1
FAST kinase domain-containing protein 1 is a protein that in humans is encoded by the FASTKD1 gene on chromosome 2.[1][2] This protein is part of the FASTKD family, which is known for regulating the energy balance of mitochondria under stress.[3] FASTKD1 is also an RNA-binding protein and has been associated with endometrial cancer.[4][5]
# Structure
FASTKD1 shares structural characteristics of the FASTKD family, including an N-terminal mitochondrial targeting domain and three C-terminal domains: two FAST kinase-like domains (FAST_1 and FAST_2) and a RNA-binding domain (RAP).[3][6] The mitochondrial targeting domain directs FASTKD1 to be imported into the mitochondria. Though the functions of the C-terminal domains are unknown, RAP possibly binds RNA during trans-splicing.[3]
# Function
As a member of the FASTKD family, FASTKD1 localizes to the mitochondria to modulate their energy balance, especially under conditions of stress. Though ubiquitously expressed in all tissues, FASTKD1 appears more abundantly in skeletal muscle, heart muscle, and other tissues enriched in mitochondria.[3] FASTKD1 has been validated as an RNA-binding protein.[4][7]
# Clinical Significance
FASTKD1 is an important apoptotic constituent. During a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response.[8] It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.
FASTKD1 has been identified as a potential molecular biomarker for endometrial cancer, a cancer of the female genital tract, most notably using uterine aspirates[5] This finding represent the basis for the development of a highly sensitive and specific minimally invasive method for the screenings of endometrial cancer. Accordingly, gene expression screening on 52 carcinoma samples and series of real-time quantitative PCR validation on 19 paired carcinomas and normal tissue samples and on 50 carcinoma and non carcinoma uterine aspirates were performed to identify and validate potential biomarkers of endometrial cancer.[5] Furthermore, another study designed a strategy to explore gene expression signatures associated with the survival in acute lymphoblastic leukemia (ALL), to search for aberrant gene activity, which consists of applying several filters to transcriptomic datasets from two pediatric ALL studies. Six genes whose expression in leukemic blasts was associated with prognosis were identified:three genes predicting poor prognosis (AK022211, FASTKD1 and STARD4) and three genes associated with a favorable outcome (CAMSAP1, PCGF6 and SH3RF3). Thus it appears that FASTKD1 may also play a role in ALL.[9] | https://www.wikidoc.org/index.php/FASTKD1 | |
f43a473d197ec66289785f9377f924623224853a | wikidoc | FASTKD2 | FASTKD2
FAST kinase domain-containing protein 2 (FASTKD2) is a protein that in humans is encoded by the FASTKD2 gene on chromosome 2. This protein is part of the FASTKD family, which is known for regulating the energy balance of mitochondria under stress. FASTKD2 has been implicated in mitochondrial encephalomyopathy, breast cancer, and prostate cancer.
# Structure
FASTKD2 shares structural characteristics of the FASTKD family, including a ~50-amino acid N-terminal mitochondrial targeting domain and three C-terminal domains: two FAST kinase-like domains (FAST_1 and FAST_2) and a RNA-binding domain (RAP). The mitochondrial targeting domain directs FASTKD2 to be imported into the mitochondria. Though the functions of the C-terminal domains are unknown, RAP possibly binds RNA during trans-splicing.
# Function
As a member of the FASTKD family, FASTKD2 localizes to the inner mitochondrial membrane to modulate their energy balance, especially under conditions of stress. Though ubiquitously expressed in all tissues, FASTKD2 appears more abundantly in skeletal muscle, heart muscle, and other tissues enriched in mitochondria. Nonetheless, FASTKD2 has been observed to mediate apoptosis independent of import into the mitochondria, suggesting that it interacts with proteins on the outer mitochondrial membrane. This protein possibly contributes its proapoptotic function through a caspase-dependent pathway, by activating proapoptotic factors or inhibiting antiapoptotic factors, but the exact mechanism remain unclear. FASTKD2 has also been validated as an RNA-binding protein.
# Clinical significance
FASTKD2 is an important apoptotic constituent. During a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response. It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.
FASTKD2 has been linked to mitochondrial encephalomyopathy associated with cytochrome c oxidase deficiency (mitochondrial complex IV deficiency). Nonsense mutations in FASTKD2 produce a truncated protein that cuts off the RAP domain and part of the FAST domains, leading to dampened sensitivity to apoptotic stimuli. Moreover, breast cancer cells are protected against apoptosis by stimulating NRIF3/DD1 expression or DIF-1 knockdown, which thus suppresses the proapoptotic function of FASTKD2. The proapoptotic function is similarly observed in prostate cancer cells, but not in other cells; it is suggested that susceptibility to FASTKD2-mediated apoptosis requires certain factors to associate with the DIF-1 complex to bind. Thus far, activating and enhancing expression of FASTKD2 may prove effective in killing breast and prostate cancer cells.
# Interactions
FASTKD2 has been shown to interact with FASTKD3. The FASTKD2 gene has been observed to bind the DIF-1 complex. | FASTKD2
FAST kinase domain-containing protein 2 (FASTKD2) is a protein that in humans is encoded by the FASTKD2 gene on chromosome 2.[1][2] This protein is part of the FASTKD family, which is known for regulating the energy balance of mitochondria under stress. FASTKD2 has been implicated in mitochondrial encephalomyopathy, breast cancer, and prostate cancer.[3][4][5]
# Structure
FASTKD2 shares structural characteristics of the FASTKD family, including a ~50-amino acid N-terminal mitochondrial targeting domain and three C-terminal domains: two FAST kinase-like domains (FAST_1 and FAST_2) and a RNA-binding domain (RAP).[3][4] The mitochondrial targeting domain directs FASTKD2 to be imported into the mitochondria. Though the functions of the C-terminal domains are unknown, RAP possibly binds RNA during trans-splicing.[3]
# Function
As a member of the FASTKD family, FASTKD2 localizes to the inner mitochondrial membrane to modulate their energy balance, especially under conditions of stress.[3][4] Though ubiquitously expressed in all tissues, FASTKD2 appears more abundantly in skeletal muscle, heart muscle, and other tissues enriched in mitochondria.[3] Nonetheless, FASTKD2 has been observed to mediate apoptosis independent of import into the mitochondria, suggesting that it interacts with proteins on the outer mitochondrial membrane. This protein possibly contributes its proapoptotic function through a caspase-dependent pathway, by activating proapoptotic factors or inhibiting antiapoptotic factors, but the exact mechanism remain unclear.[4][5] FASTKD2 has also been validated as an RNA-binding protein.[6][7]
# Clinical significance
FASTKD2 is an important apoptotic constituent. During a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response.[8] It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.
FASTKD2 has been linked to mitochondrial encephalomyopathy associated with cytochrome c oxidase deficiency (mitochondrial complex IV deficiency). Nonsense mutations in FASTKD2 produce a truncated protein that cuts off the RAP domain and part of the FAST domains, leading to dampened sensitivity to apoptotic stimuli.[3][6] Moreover, breast cancer cells are protected against apoptosis by stimulating NRIF3/DD1 expression or DIF-1 knockdown, which thus suppresses the proapoptotic function of FASTKD2.[4] The proapoptotic function is similarly observed in prostate cancer cells, but not in other cells; it is suggested that susceptibility to FASTKD2-mediated apoptosis requires certain factors to associate with the DIF-1 complex to bind.[5] Thus far, activating and enhancing expression of FASTKD2 may prove effective in killing breast and prostate cancer cells.[4][5]
# Interactions
FASTKD2 has been shown to interact with FASTKD3.[3] The FASTKD2 gene has been observed to bind the DIF-1 complex.[4] | https://www.wikidoc.org/index.php/FASTKD2 | |
d02283e5b40e70a5d2df016ecffed0b7467eb0d4 | wikidoc | FASTKD3 | FASTKD3
FAST kinase domain-containing protein 3 (FASTKD3) is a protein that in humans is encoded by the FASTKD3 gene on chromosome 5. This protein is part of the Fas-activated serine/threonine kinase domain (FASTKD) containing protein family, which is known for regulating the energy balance of mitochondria under stress.
# Structure
FASTKD3 shares structural characteristics of the FASTKD family, including an N-terminal mitochondrial targeting domain and three C-terminal domains: two FAST kinase-like domains (FAST_1 and FAST_2) and a RNA-binding domain (RAP). The mitochondrial targeting domain directs FASTKD3 to be imported into the mitochondria. Though the functions of the C-terminal domains are unknown, RAP possibly binds RNA during trans-splicing.
# Function
As a member of the FASTKD family, FASTKD3 localizes to the mitochondria to modulate their energy balance, especially under conditions of stress. Though ubiquitously expressed in all tissues, FASTKD3 appears more abundantly in skeletal muscle, heart muscle, and other tissues enriched in mitochondria. FASTKD3 has been proposed to regulate energy production by serving as a scaffold protein that brings together RNA processing/translation and respiratory components.
# Clinical Significance
Currently, FASTKD3 has not been linked to any disease. (Dated: September 17, 2015)
# Interactions
FASTKD3 has been shown to interact with:
- FASTKD2;
- Fatty acid beta oxidation pathway proteins (ACADVL, ECHS1, HADHA, HADHB, ACAA2);
- Amino acid catabolic pathways proteins (MCCC1, MCCC2, GLUD1, HIBADH, CPS1);
- Amino acid biosynthesis proteins (PYCR1, PYCR2, ALDH18A1, SHMT2, GLS);
- TCA cycle proteins (IDH3A, IDH2, SUCLG2, DLST);
- Respiratory chain proteins (NDUFS1, SDHA, ATP5A1, ETFA, ETFB);
- Mitochondrial RNA processing proteins (LRPPRC, DHX30, PNPT1); and
- Mitochondrial translation proteins (TUFM, GFM1, IARS2, MRPS22, TARS2, MRPS2, PTCD1, MTO1, MRPS31). | FASTKD3
FAST kinase domain-containing protein 3 (FASTKD3) is a protein that in humans is encoded by the FASTKD3 gene on chromosome 5.[1][2] This protein is part of the Fas-activated serine/threonine kinase domain (FASTKD) containing protein family, which is known for regulating the energy balance of mitochondria under stress.[3][4]
# Structure
FASTKD3 shares structural characteristics of the FASTKD family, including an N-terminal mitochondrial targeting domain and three C-terminal domains: two FAST kinase-like domains (FAST_1 and FAST_2) and a RNA-binding domain (RAP).[3][4] The mitochondrial targeting domain directs FASTKD3 to be imported into the mitochondria. Though the functions of the C-terminal domains are unknown, RAP possibly binds RNA during trans-splicing.[3]
# Function
As a member of the FASTKD family, FASTKD3 localizes to the mitochondria to modulate their energy balance, especially under conditions of stress. Though ubiquitously expressed in all tissues, FASTKD3 appears more abundantly in skeletal muscle, heart muscle, and other tissues enriched in mitochondria. FASTKD3 has been proposed to regulate energy production by serving as a scaffold protein that brings together RNA processing/translation and respiratory components.[3]
# Clinical Significance
Currently, FASTKD3 has not been linked to any disease. (Dated: September 17, 2015)
# Interactions
FASTKD3 has been shown to interact with:
- FASTKD2;
- Fatty acid beta oxidation pathway proteins (ACADVL, ECHS1, HADHA, HADHB, ACAA2);
- Amino acid catabolic pathways proteins (MCCC1, MCCC2, GLUD1, HIBADH, CPS1);
- Amino acid biosynthesis proteins (PYCR1, PYCR2, ALDH18A1, SHMT2, GLS);
- TCA cycle proteins (IDH3A, IDH2, SUCLG2, DLST);
- Respiratory chain proteins (NDUFS1, SDHA, ATP5A1, ETFA, ETFB);
- Mitochondrial RNA processing proteins (LRPPRC, DHX30, PNPT1); and
- Mitochondrial translation proteins (TUFM, GFM1, IARS2, MRPS22, TARS2, MRPS2, PTCD1, MTO1, MRPS31).[3] | https://www.wikidoc.org/index.php/FASTKD3 | |
0764cd49b8064e73c378994d648858b2173a225b | wikidoc | FASTKD5 | FASTKD5
FAST kinase domain-containing protein 5 (FASTKD5) is a protein that in humans is encoded by the FASTKD5 gene on chromosome 20. This protein is part of the FASTKD family, which is known for regulating the energy balance of mitochondria under stress. FASTKD5 is also required for RNA granules to process precursor mRNAs not flanked by tRNAs.
# Structure
FASTKD5 shares structural characteristics of the FASTKD family, including an amino terminal mitochondrial targeting domain and three C-terminal domains: two FAST kinase-like domains (FAST_1 and FAST_2) and a RNA-binding domain (RAP). The mitochondrial targeting domain directs FASTKD5 to be imported into the mitochondria. Though the functions of the C-terminal domains are unknown, RAP possibly binds RNA during trans-splicing. This protein forms a 103 kDa protein complex with unidentified proteins.
# Function
As a member of the FASTKD family, FASTKD5 localizes to the mitochondria to modulate their energy balance, especially under conditions of stress. Though ubiquitously expressed in all tissues, FASTKD5 appears more abundantly in skeletal muscle, heart muscle, and other tissues enriched in mitochondria. FASTKD5 also localizes to RNA granules, membraneless bodies containing mRNAs and associated RNA-binding proteins, where it facilitates posttranscriptional RNA processing. This protein is required for the maturation of precursor mRNAs that are not flanked by tRNAs, and thus cannot be processed by the canonical mRNA maturation pathway.
# Clinical significance
Though the link to FASTKD5 remains uncharacterized, the accumulation of abnormal RNA granules can lead to some neurodegenerative diseases.
# Interactions
FASTKD5 has been shown to interact with:
- FASTKD2,
- DHX30, and
- GRSF1. | FASTKD5
FAST kinase domain-containing protein 5 (FASTKD5) is a protein that in humans is encoded by the FASTKD5 gene on chromosome 20.[1][2] This protein is part of the FASTKD family, which is known for regulating the energy balance of mitochondria under stress.[3][4] FASTKD5 is also required for RNA granules to process precursor mRNAs not flanked by tRNAs.[5]
# Structure
FASTKD5 shares structural characteristics of the FASTKD family, including an amino terminal mitochondrial targeting domain and three C-terminal domains: two FAST kinase-like domains (FAST_1 and FAST_2) and a RNA-binding domain (RAP).[3][4] The mitochondrial targeting domain directs FASTKD5 to be imported into the mitochondria. Though the functions of the C-terminal domains are unknown, RAP possibly binds RNA during trans-splicing.[3] This protein forms a 103 kDa protein complex with unidentified proteins.[5]
# Function
As a member of the FASTKD family, FASTKD5 localizes to the mitochondria to modulate their energy balance, especially under conditions of stress. Though ubiquitously expressed in all tissues, FASTKD5 appears more abundantly in skeletal muscle, heart muscle, and other tissues enriched in mitochondria.[3] FASTKD5 also localizes to RNA granules, membraneless bodies containing mRNAs and associated RNA-binding proteins, where it facilitates posttranscriptional RNA processing. This protein is required for the maturation of precursor mRNAs that are not flanked by tRNAs, and thus cannot be processed by the canonical mRNA maturation pathway.[5]
# Clinical significance
Though the link to FASTKD5 remains uncharacterized, the accumulation of abnormal RNA granules can lead to some neurodegenerative diseases.[5]
# Interactions
FASTKD5 has been shown to interact with:
- FASTKD2,[5]
- DHX30,[5] and
- GRSF1.[5] | https://www.wikidoc.org/index.php/FASTKD5 | |
78e48603738dd7e756bf26197af5a16790d848dc | wikidoc | FOLFIRI | FOLFIRI
# Overview
FOLFIRI is a chemotherapy regimen for treatment of colorectal cancer, made up of the drugs
- FOL – folinic acid (leucovorin)
- F – fluorouracil (5-FU)
- IRI – irinotecan (Camptosar)
The regimen consists of:
- Irinotecan (180 mg/m² IV over 90 minutes) concurrently with folinic acid (400 mg/m² IV over 120 minutes).
- Followed by fluorouracil (400-500 mg/m² IV bolus) then fluorouracil (2400-3000mg/m² intravenous infusion over 46 hours).
This cycle is typically repeated every two weeks.
The dosages shown above may vary from cycle to cycle.
# See Also
- FOLFOX
de:FOLFIRI | FOLFIRI
# Overview
FOLFIRI is a chemotherapy regimen for treatment of colorectal cancer, made up of the drugs
- FOL – folinic acid (leucovorin)
- F – fluorouracil (5-FU)
- IRI – irinotecan (Camptosar)
The regimen consists of:
- Irinotecan (180 mg/m² IV over 90 minutes) concurrently with folinic acid (400 mg/m² [or 2 x 250 mg/m²] IV over 120 minutes).
- Followed by fluorouracil (400-500 mg/m² IV bolus) then fluorouracil (2400-3000mg/m² intravenous infusion over 46 hours).
This cycle is typically repeated every two weeks.
The dosages shown above may vary from cycle to cycle.
# See Also
- FOLFOX
Template:Chemotherapeutic Agents
de:FOLFIRI
Template:WH
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/FOLFIRI |
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