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63aa4186f5f28ae018e8f00da31868fc82ecfe06 | wikidoc | SLC19A3 | SLC19A3
Thiamine transporter 2 (ThTr-2), also known as solute carrier family 19 member 3, is a protein that in humans is encoded by the SLC19A3 gene. SLC19A3 is a thiamine transporter.
# Function
ThTr-2 is a ubiquitously expressed transmembrane thiamine transporter that lacks folate transport activity.
It is specifically inhibited by chloroquine.
# Clinical significance
Mutations in this gene cause biotin-responsive basal ganglia disease (BBGD); a recessive disorder manifested in childhood that progresses to chronic encephalopathy, dystonia, quadriparesis, and death if untreated. Patients with BBGD have bilateral necrosis in the head of the caudate nucleus and in the putamen. Administration of high doses of biotin in the early progression of the disorder eliminates pathological symptoms while delayed treatment results in residual paraparesis, mild mental retardation, or dystonia. Administration of thiamine is ineffective in the treatment of this disorder. Experiments have failed to show that this protein can transport biotin. Mutations in this gene also cause a Wernicke's-like encephalopathy. | SLC19A3
Thiamine transporter 2 (ThTr-2), also known as solute carrier family 19 member 3, is a protein that in humans is encoded by the SLC19A3 gene.[1][2][3] SLC19A3 is a thiamine transporter.
# Function
ThTr-2 is a ubiquitously expressed transmembrane thiamine transporter that lacks folate transport activity.[1]
It is specifically inhibited by chloroquine.[4]
# Clinical significance
Mutations in this gene cause biotin-responsive basal ganglia disease (BBGD); a recessive disorder manifested in childhood that progresses to chronic encephalopathy, dystonia, quadriparesis, and death if untreated. Patients with BBGD have bilateral necrosis in the head of the caudate nucleus and in the putamen. Administration of high doses of biotin in the early progression of the disorder eliminates pathological symptoms while delayed treatment results in residual paraparesis, mild mental retardation, or dystonia. Administration of thiamine is ineffective in the treatment of this disorder. Experiments have failed to show that this protein can transport biotin. Mutations in this gene also cause a Wernicke's-like encephalopathy.[1] | https://www.wikidoc.org/index.php/SLC19A3 | |
0b52f54f52a66bf48dc4f6c0f24f513c20717bdd | wikidoc | SLC20A2 | SLC20A2
Sodium-dependent phosphate transporter 2 is a protein that in humans is encoded by the SLC20A2 gene.
# Genomics
This gene is found on the short arm of chromosome 8 (8p12-p11) on the minus (Crick) strand. It is 123,077 bases in length. The encoded protein has 652 amino acids and the predicted molecular weight of the protein is 70.392 kiloDaltons.
# Function
The protein acts as a homodimer and is involved in phosphate transport by absorbing phosphate from interstitial fluid for normal cellular functions such as cellular metabolism, signal transduction, and nucleic acid and lipid synthesis.
# Clinical significance
Mutations in the SLC20a2 gene are associated with idiopathic basal ganglia calcification (Fahr's syndrome). This association suggests that familial idiopathic basal ganglia calcification is caused by changes in phosphate homeostasis, since this gene encodes for PIT-2, an inorganic phosphate transporter. | SLC20A2
Sodium-dependent phosphate transporter 2 is a protein that in humans is encoded by the SLC20A2 gene.[1][2][3]
# Genomics
This gene is found on the short arm of chromosome 8 (8p12-p11) on the minus (Crick) strand. It is 123,077 bases in length. The encoded protein has 652 amino acids and the predicted molecular weight of the protein is 70.392 kiloDaltons.
# Function
The protein acts as a homodimer and is involved in phosphate transport by absorbing phosphate from interstitial fluid for normal cellular functions such as cellular metabolism, signal transduction, and nucleic acid and lipid synthesis.
# Clinical significance
Mutations in the SLC20a2 gene are associated with idiopathic basal ganglia calcification (Fahr's syndrome). This association suggests that familial idiopathic basal ganglia calcification is caused by changes in phosphate homeostasis, since this gene encodes for PIT-2, an inorganic phosphate transporter.[4] | https://www.wikidoc.org/index.php/SLC20A2 | |
acc3e054a0e1e6293f11e3be6b741fa6c3908e57 | wikidoc | SLC22A1 | SLC22A1
Solute carrier family 22 member 1 is a protein that in humans is encoded by the gene SLC22A1.
# Function
Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter.
It is also required for the uptake of metformin by cells. | SLC22A1
Solute carrier family 22 member 1 is a protein that in humans is encoded by the gene SLC22A1.[1][2]
# Function
Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter.[2]
It is also required for the uptake of metformin by cells.[3][4] | https://www.wikidoc.org/index.php/SLC22A1 | |
17ffd036c72d29d624e12812d87bba48f2af898d | wikidoc | SLC22A3 | SLC22A3
Solute carrier family 22 member 3 (SLC22A3) also known as the organic cation transporter 3 (OCT3) or extraneuronal monoamine transporter (EMT) is a protein that in humans is encoded by the SLC22A3 gene.
Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein.
# Distribution
OCT3 is widely distributed in brain tissue. It is not yet completely clear whether its location is primarily neuronal or glial. Areas of the brain in which it has been reported include: hippocampus, retrosplenial cortex, visual cortex, hypothalamus, amygdala, nucleus accumbens, thalamus, raphe nucleus, subiculum, superior and inferior colliculi, and islands of Calleja.
# Pharmacology
Organic cation transporter 3 is a polyspecific transporter whose transport is independent of sodium. Known substrates for transport include: histamine, serotonin, norepinephrine, dopamine and MPP+. Capacity for transport and affinity for these substrates may vary between rat and human isoforms however.
Transport activity of OCT3 is inhibited by recreational and pharmaceutical drugs, including MDMA, phencyclidine (PCP), MK-801, amphetamine, methamphetamine and cocaine. Transport is also inhibited by the chemical decynium-22 and physiological concentrations of corticosterone and cortisol. Ki values for decynium-22 and corticosterone inhibition of OCT3 transport are respectively 10 and 100 times lower than Ki values of OCT1 and OCT2. | SLC22A3
Solute carrier family 22 member 3 (SLC22A3) also known as the organic cation transporter 3 (OCT3) or extraneuronal monoamine transporter (EMT) is a protein that in humans is encoded by the SLC22A3 gene.[1][2][3]
Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein.[3]
# Distribution
OCT3 is widely distributed in brain tissue. It is not yet completely clear whether its location is primarily neuronal or glial. Areas of the brain in which it has been reported include: hippocampus, retrosplenial cortex, visual cortex, hypothalamus, amygdala, nucleus accumbens, thalamus, raphe nucleus, subiculum, superior and inferior colliculi, and islands of Calleja.[4][5]
# Pharmacology
Organic cation transporter 3 is a polyspecific transporter whose transport is independent of sodium. Known substrates for transport include: histamine, serotonin, norepinephrine, dopamine and MPP+. Capacity for transport and affinity for these substrates may vary between rat and human isoforms however.[5]
Transport activity of OCT3 is inhibited by recreational and pharmaceutical drugs, including MDMA, phencyclidine (PCP), MK-801, amphetamine, methamphetamine and cocaine.[5] Transport is also inhibited by the chemical decynium-22 and physiological concentrations of corticosterone and cortisol. Ki values for decynium-22 and corticosterone inhibition of OCT3 transport are respectively 10 and 100 times lower than Ki values of OCT1 and OCT2.[6] | https://www.wikidoc.org/index.php/SLC22A3 | |
08f9236b791793d4bcfbafc1bfcd15aa0fc1f014 | wikidoc | SLC22A5 | SLC22A5
SLC22A5 is a membrane transport protein associated with primary carnitine deficiency. This protein is involved in the active cellular uptake of carnitine. It acts a symporter, moving sodium ions and other organic cations across the membrane along with carnitine. Such polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for the elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. Mutations in the SLC22A5 gene cause systemic primary carnitine deficiency, which can lead to heart failure.
# Structure
The SLC22A5 gene, containing 10 exons, is located on the q arm of chromosome 5 in position 31.1 and spans 25,910 base pair. The gene produces a 63 kDa protein composed of 557 amino acids. The protein has 12 putative transmembrane domains, with a long extracellular loop of 107 amino acids between the first two transmembrane domains and an intracellular loop between the fourth and fifth transmembrane domains. This long extracellular loop has three potential sites for N-glycosylation, and the intracellular loop has an ATP/GTP binding motif. In putative intracellular domains, there are five potential sites for protein-kinase C-dependent phosphorylation and one for protein-kinase A-dependent phosphorylation.
# Function
The SLC22A5 gene codes for a plasma integral membrane protein which functions as both an organic cation transporter and a sodium-dependent high affinity carnitine transporter. The encoded protein is involved in the active cellular uptake of carnitine, transporting one sodium ion with one molecule of carnitine. Organic cations transported by this protein include tetraethylammonium (TEA) without involvement of sodium. The relative uptake activity ratio of carnitine to TEA is 11.3.
# Clinical Significance
The main phenotypical effect of autosomal recessive mutations, either compound heterozygous or homozygous, in the SLC22A5 gene is systemic primary carnitine deficiency, characterized by impaired carnitine transport, urinary carnitine wasting, low serum carnitine levels, reduced intracellular carnitine accumulation, impaired beta oxidation, and cytosolic fatty acid accumulation. Patients often display metabolic decompensation, hypoketotic hypoglycemia, hepatic encephalopathy, Reye syndrome, and sudden infant death in their first year, followed by the later onset of cardiomyopathy or skeletal myopathy, arrhythmias, muscle weakness, and heart failure in early childhood. Patients may be asymptomatic, with about 70% of asymptomatic patients having a missense mutation or in-frame deletion; nonsense mutation frequency is increased in symptomatic patients. The symptoms and outcome of the disease can be drastically improved by replacement therapy with L-carnitine. The estimated incidence of primary carnitine deficiency in newborns is about 1 in 40,000.
# Interactions
SLC22A5 interacts with PDZK1. | SLC22A5
SLC22A5 is a membrane transport protein associated with primary carnitine deficiency. This protein is involved in the active cellular uptake of carnitine. It acts a symporter, moving sodium ions and other organic cations across the membrane along with carnitine. Such polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for the elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins.[1] Mutations in the SLC22A5 gene cause systemic primary carnitine deficiency, which can lead to heart failure.[2]
# Structure
The SLC22A5 gene, containing 10 exons,[3] is located on the q arm of chromosome 5 in position 31.1 and spans 25,910 base pair.[1] The gene produces a 63 kDa protein composed of 557 amino acids.[4][5] The protein has 12 putative transmembrane domains, with a long extracellular loop of 107 amino acids between the first two transmembrane domains and an intracellular loop between the fourth and fifth transmembrane domains. This long extracellular loop has three potential sites for N-glycosylation, and the intracellular loop has an ATP/GTP binding motif. In putative intracellular domains, there are five potential sites for protein-kinase C-dependent phosphorylation and one for protein-kinase A-dependent phosphorylation.[6]
# Function
The SLC22A5 gene codes for a plasma integral membrane protein which functions as both an organic cation transporter and a sodium-dependent high affinity carnitine transporter.[1] The encoded protein is involved in the active cellular uptake of carnitine, transporting one sodium ion with one molecule of carnitine. Organic cations transported by this protein include tetraethylammonium (TEA) without involvement of sodium. The relative uptake activity ratio of carnitine to TEA is 11.3.[7]
# Clinical Significance
The main phenotypical effect of autosomal recessive mutations, either compound heterozygous or homozygous,[2] in the SLC22A5 gene is systemic primary carnitine deficiency,[3] characterized by impaired carnitine transport, urinary carnitine wasting, low serum carnitine levels, reduced intracellular carnitine accumulation, impaired beta oxidation, and cytosolic fatty acid accumulation.[2] Patients often display metabolic decompensation, hypoketotic hypoglycemia, hepatic encephalopathy, Reye syndrome, and sudden infant death in their first year, followed by the later onset of cardiomyopathy or skeletal myopathy, arrhythmias, muscle weakness, and heart failure in early childhood.[2][8][9] Patients may be asymptomatic, with about 70% of asymptomatic patients having a missense mutation or in-frame deletion; nonsense mutation frequency is increased in symptomatic patients.[10] The symptoms and outcome of the disease can be drastically improved by replacement therapy with L-carnitine.[11] The estimated incidence of primary carnitine deficiency in newborns is about 1 in 40,000.[12]
# Interactions
SLC22A5 interacts with PDZK1.[7] | https://www.wikidoc.org/index.php/SLC22A5 | |
c4edb08913ec5052aa31e30cb8b2a541fd5de4e0 | wikidoc | SLC22A7 | SLC22A7
Solute carrier family 22 member 7 is a protein that in humans is encoded by the gene SLC22A7.
The protein encoded by this gene is involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Alternatively spliced transcript variants encoding different isoforms have been described.
# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.
- ↑ The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | SLC22A7
Solute carrier family 22 member 7 is a protein that in humans is encoded by the gene SLC22A7.[1][2][3]
The protein encoded by this gene is involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Alternatively spliced transcript variants encoding different isoforms have been described.[3]
# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
- ↑ The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | https://www.wikidoc.org/index.php/SLC22A7 | |
71b8538ed2c8285b9aa25dbf4dcb58cd6f779169 | wikidoc | SLC24A5 | SLC24A5
Sodium/potassium/calcium exchanger 5 (NCKX5), also known as solute carrier family 24 member 5 (SLC24A5), is a protein that in humans is encoded by the SLC24A5 gene that has a major influence on natural skin colour variation. The NCKX5 protein is a member of the potassium-dependent sodium/calcium exchanger family. Sequence variation in the SLC24A5 gene, particularly a non-synonymous SNP changing the amino acid at position 111 in NCKX5 from alanine to threonine, has been associated with differences in skin pigmentation.
The SLC24A5 gene's derived threonine or Ala111Thr allele (rs1426654) has been shown to be a major factor in the light skin tone of Europeans compared to Sub-Saharan Africans, and is believed to represent as much as 25–40% of the average skin tone difference between Europeans and West Africans. It has been the subject of recent selection in Europe, and is fixed in European populations.
# Gene
The SLC24A5 gene, in humans, is located on the long (q) arm of chromosome 15 on position 21.1, from base pair 46,200,461 to base pair 46,221,881.
# Protein
NCKX5 is 43 kDa protein that is partially localized to the trans-Golgi network in melanocytes. Removal of the NCKX5 protein disrupts melanogenesis in human and mouse melanocytes, causing a significant reduction in melanin pigment production. Site-directed mutagenesis corresponding to a non-synonymous single nucleotide polymorphism in SLC24A5 alters a residue in NCKX5 (A111T) that is important for NCKX5 sodium-calcium exchanger activity.
# Effect on skin color
SLC24A5 appears to have played a key role in the evolution of light skin in humans of European ancestry. The gene's function in pigmentation was discovered in zebrafish as a result of the positional cloning of the gene responsible for the "golden" variety of this common pet store fish. Evidence in the International HapMap Project database of genetic variation in human populations showed that Europeans, represented by the "CEU" population, had two primary alleles differing by only one nucleotide, changing the 111th amino acid from alanine to threonine, abbreviated "A111T".
The derived threonine allele (Ala111Thr; also known as A111T or Thr111) represented 98.7 to 100% of the alleles in European samples, while the ancestral or alanine form was found in 93 to 100% of samples of Sub-Saharan Africans, East Asians and Indigenous Americans. The variation is a SNP polymorphism rs1426654, which had been previously shown to be second among 3011 tabulated SNPs ranked as ancestry-informative markers. This single change in SLC24A5 explains between 25 and 38% of the difference in skin melanin index between peoples of sub-Saharan African and European ancestry.
The SNP rs2470102 independently affect skin pigmentation variation among the South Asian population.
Furthermore, the European mutation is associated with the largest region of diminished genetic variation in the CEU HapMap population, suggesting the possibility that the A111T mutation may be the subject of the single largest degree of selection in human populations of European ancestry. It is theorised that selection for the derived allele is based on the need for sunlight to produce the essential nutrient vitamin D. In northerly latitudes, where there is less sun, greater requirement for body coverage due to colder climate, and frequently, diets poor in vitamin D, making lighter skin more suitable for survival. Tests for this variation have obvious application to forensic science.
The earliest known sample of the threonine allele is 13,000 years old from Satsurblia Cave in Georgia. The allele was widespread from Anatolia to Iran at the beginning of the Neolithic, and was introduced to Europe with the arrival of the first farmers from this region about 8,000 years ago. | SLC24A5
Sodium/potassium/calcium exchanger 5 (NCKX5), also known as solute carrier family 24 member 5 (SLC24A5), is a protein that in humans is encoded by the SLC24A5 gene that has a major influence on natural skin colour variation.[1] The NCKX5 protein is a member of the potassium-dependent sodium/calcium exchanger family. Sequence variation in the SLC24A5 gene, particularly a non-synonymous SNP changing the amino acid at position 111 in NCKX5 from alanine to threonine, has been associated with differences in skin pigmentation.[2]
The SLC24A5 gene's derived threonine or Ala111Thr allele (rs1426654[3]) has been shown to be a major factor in the light skin tone of Europeans compared to Sub-Saharan Africans, and is believed to represent as much as 25–40% of the average skin tone difference between Europeans and West Africans.[1][4] It has been the subject of recent selection in Europe, and is fixed in European populations.[5][6][7]
# Gene
The SLC24A5 gene, in humans, is located on the long (q) arm of chromosome 15 on position 21.1, from base pair 46,200,461 to base pair 46,221,881.[1]
# Protein
NCKX5 is 43 kDa protein that is partially localized to the trans-Golgi network in melanocytes. Removal of the NCKX5 protein disrupts melanogenesis in human and mouse melanocytes, causing a significant reduction in melanin pigment production. Site-directed mutagenesis corresponding to a non-synonymous single nucleotide polymorphism in SLC24A5 alters a residue in NCKX5 (A111T) that is important for NCKX5 sodium-calcium exchanger activity.[2]
# Effect on skin color
SLC24A5 appears to have played a key role in the evolution of light skin in humans of European ancestry. The gene's function in pigmentation was discovered in zebrafish as a result of the positional cloning of the gene responsible for the "golden" variety of this common pet store fish. Evidence in the International HapMap Project database of genetic variation in human populations showed that Europeans, represented by the "CEU" population, had two primary alleles differing by only one nucleotide, changing the 111th amino acid from alanine to threonine, abbreviated "A111T".[1][8][9]
The derived threonine allele (Ala111Thr; also known as A111T or Thr111) represented 98.7 to 100% of the alleles in European samples, while the ancestral or alanine form was found in 93 to 100% of samples of Sub-Saharan Africans, East Asians and Indigenous Americans. The variation is a SNP polymorphism rs1426654, which had been previously shown to be second among 3011 tabulated SNPs ranked as ancestry-informative markers. This single change in SLC24A5 explains between 25 and 38% of the difference in skin melanin index between peoples of sub-Saharan African and European ancestry.[1]
The SNP rs2470102 independently affect skin pigmentation variation among the South Asian population.[10]
Furthermore, the European mutation is associated with the largest region of diminished genetic variation in the CEU HapMap population, suggesting the possibility that the A111T mutation may be the subject of the single largest degree of selection in human populations of European ancestry.[1] It is theorised that selection for the derived allele is based on the need for sunlight to produce the essential nutrient vitamin D. In northerly latitudes, where there is less sun, greater requirement for body coverage due to colder climate, and frequently, diets poor in vitamin D, making lighter skin more suitable for survival.[11] Tests for this variation have obvious application to forensic science.
The earliest known sample of the threonine allele is 13,000 years old from Satsurblia Cave in Georgia.[12] The allele was widespread from Anatolia to Iran at the beginning of the Neolithic, and was introduced to Europe with the arrival of the first farmers from this region about 8,000 years ago.[13][14] | https://www.wikidoc.org/index.php/SLC24A5 | |
5a0ba2758e0c694113aea2572afd37251de60e77 | wikidoc | SLC25A1 | SLC25A1
The tricarboxylate transport protein, also referred to as citrate carrier (CIC), tricarboxylate carrier, or citrate transport protein, is part of the mitochondrial carrier gene family SLC25. It is a protein in humans encoded by the SLC25A1 gene. High levels of the tricarboxylate transport protein are found in the liver, pancreas and kidney. Lower or no levels are present in the brain, heart, skeletal muscle, placenta and lung.
The tricarboxylate transport protein is located within the inner mitochondria membrane. It provides a link between the mitochondrial matrix and cytosol by transporting citrate through the impermeable inner mitochondrial membrane in exchange for malate from the cytosol. The citrate transported out of the mitochondrial matrix by the tricarboxylate transport protein is catalyzed by citrate lyase to acetyl CoA, the starting material for fatty acid biosynthesis, and oxaloacetate. As well, cytosolic NADPH + H+ necessary for fatty acid biosynthesis is generated in the reduction of oxaloacetate to malate and pyruvate by malate deydrogenase and the malic enzyme. For these reasons, the tricarboxylate transport protein is considered to play a key role in fatty acid synthesis.
# Structure
The structure of the tricarboxylate transport protein is consistent with the structures of other mitochondrial carriers. In particular, the tricarboxylate transport protein has a tripartite structure consisting of three repeated domains that are approximately 100 amino acids in length. Each repeat forms a transmembrane domain consisting of two hydrophobic α-helices. The amino and carboxy termini are located on the cytosolic side of the inner mitochondrial membrane. Each domain is linked by two hydrophilic loops located on the cytosolic side of the membrane. The two α-helices of each repeated domain are connected by hydrophilic loops located on the matrix side of the membrane. A salt bridge network is present on both the matrix side and cytoplasmic side of the tricarboxylate transport protein.
# Transport mechanism
The tricarboxylate transport protein exists in two states: a cytoplasmic state where it accepts malate from the cytoplasm and a matrix state where it accepts citrate from the mitochondrial matrix. A single binding site is present near the center of the cavity of the tricarboxylate transport protein, which can be either exposed to the cytosol or the mitochondrial matrix depending on the state. A substrate induced conformational change occurs when citrate enters from the matrix side and binds to the central cavity of the tricarboxylate transport protein. This conformational change opens a gate on the cytosolic side and closes the gate on the matrix side. Likewise, when malate enters from the cytosolic side, the matrix gate opens and the cytosolic gate closes. Each side of the transporter is open and closed by the disruption and formation of the salt bridge networks, which allows access to the single binding site.
# Disease relevance
Mutations in this gene have been associated with the inborn error of metabolism combined D-2- and L-2-hydroxyglutaric aciduria, which was the first reported case of a pathogenic mutation of the SLC25A1 gene. Patients with D-2/L-2-hydroxyglutaric aciduria display neonatal onset metabolic encephalopathy, infantile epilepsy, global developmental delay, muscular hypotonia and early death. It is believed low levels of citrate in the cytosol and high levels of citrate in the mitochondria caused by the impaired citrate transport plays a role in the disease. In addition, increased expression of the tricarboxylate transport protein has been linked to cancer and the production of inflammatory mediators. Therefore, it has been suggested that inhibition of the tricarboxylate transport protein may have a therapeutic effect in chronic inflammation diseases and cancer. | SLC25A1
The tricarboxylate transport protein, also referred to as citrate carrier (CIC), tricarboxylate carrier, or citrate transport protein, is part of the mitochondrial carrier gene family SLC25.[1][2][3] It is a protein in humans encoded by the SLC25A1 gene.[4][5][6] High levels of the tricarboxylate transport protein are found in the liver, pancreas and kidney. Lower or no levels are present in the brain, heart, skeletal muscle, placenta and lung.[1][3]
The tricarboxylate transport protein is located within the inner mitochondria membrane. It provides a link between the mitochondrial matrix and cytosol by transporting citrate through the impermeable inner mitochondrial membrane in exchange for malate from the cytosol.[1][2][3][7] The citrate transported out of the mitochondrial matrix by the tricarboxylate transport protein is catalyzed by citrate lyase to acetyl CoA, the starting material for fatty acid biosynthesis, and oxaloacetate.[2] As well, cytosolic NADPH + H+ necessary for fatty acid biosynthesis is generated in the reduction of oxaloacetate to malate and pyruvate by malate deydrogenase and the malic enzyme.[3][8][9] For these reasons, the tricarboxylate transport protein is considered to play a key role in fatty acid synthesis.[2]
# Structure
The structure of the tricarboxylate transport protein is consistent with the structures of other mitochondrial carriers.[1][2][7] In particular, the tricarboxylate transport protein has a tripartite structure consisting of three repeated domains that are approximately 100 amino acids in length.[1][7] Each repeat forms a transmembrane domain consisting of two hydrophobic α-helices.[1][2][10] The amino and carboxy termini are located on the cytosolic side of the inner mitochondrial membrane.[1][2] Each domain is linked by two hydrophilic loops located on the cytosolic side of the membrane.[1][2][10][11] The two α-helices of each repeated domain are connected by hydrophilic loops located on the matrix side of the membrane.[1][2][11] A salt bridge network is present on both the matrix side and cytoplasmic side of the tricarboxylate transport protein.[11]
# Transport mechanism
The tricarboxylate transport protein exists in two states: a cytoplasmic state where it accepts malate from the cytoplasm and a matrix state where it accepts citrate from the mitochondrial matrix.[12] A single binding site is present near the center of the cavity of the tricarboxylate transport protein, which can be either exposed to the cytosol or the mitochondrial matrix depending on the state.[10][11][12] A substrate induced conformational change occurs when citrate enters from the matrix side and binds to the central cavity of the tricarboxylate transport protein.[1] This conformational change opens a gate on the cytosolic side and closes the gate on the matrix side.[1] Likewise, when malate enters from the cytosolic side, the matrix gate opens and the cytosolic gate closes.[1] Each side of the transporter is open and closed by the disruption and formation of the salt bridge networks, which allows access to the single binding site.[10][11][12][13][14]
# Disease relevance
Mutations in this gene have been associated with the inborn error of metabolism combined D-2- and L-2-hydroxyglutaric aciduria,[15] which was the first reported case of a pathogenic mutation of the SLC25A1 gene.[11][16] Patients with D-2/L-2-hydroxyglutaric aciduria display neonatal onset metabolic encephalopathy, infantile epilepsy, global developmental delay, muscular hypotonia and early death.[11][16][17] It is believed low levels of citrate in the cytosol and high levels of citrate in the mitochondria caused by the impaired citrate transport plays a role in the disease.[11][17] In addition, increased expression of the tricarboxylate transport protein has been linked to cancer[3][18][19] and the production of inflammatory mediators.[20][21][22] Therefore, it has been suggested that inhibition of the tricarboxylate transport protein may have a therapeutic effect in chronic inflammation diseases and cancer.[21] | https://www.wikidoc.org/index.php/SLC25A1 | |
46d486f25811f1ba2776bc337f1d1ef0aba7c786 | wikidoc | SLC25A3 | SLC25A3
Phosphate carrier protein, mitochondrial is a protein that in humans is encoded by the SLC25A3 gene. The encoded protein is a transmembrane protein located in the mitochondrial inner membrane and catalyzes the transport of phosphate ions across it for the purpose of oxidative phosphorylation. There are two significant isoforms of this gene expressed in human cells, which differ slightly in structure and function. Mutations in this gene can cause mitochondrial phosphate carrier deficiency (MPCD), a fatal disorder of oxidative phosphorylation symptomized by lactic acidosis, neonatal hypotonia, hypertrophic cardiomyopathy, and death within the first year of life.
# Structure
The SLC25A3 gene is located on the q arm of chromosome 12 in position 23.1 and spans 8,376 base pairs. The gene has 9 exons and produces a 40.1 kDa protein composed of 362 amino acids. The encoded protein (PHC) is a multi-pass transmembrane protein located in the mitochondrial inner membrane; it contains six transmembrane segments, emerging into a large extramembranous loop. Both the N-terminal and C-terminal regions of this protein protrude toward the cytosol. PHC contains three related segments arranged in tandem which are related to those found in other characterized members of the mitochondrial carrier family. There exist two transcript variants of this protein, PHC-A and PHC-B, which differ by 13 amino acids. Isoform A contains 42 amino acids while Isoform B contains 41. In vitro, the isoforms differ in their substrate affinities and transport rates.
# Function
The encoded protein (PHC) catalyzes the transport of phosphate from the cytosol into the mitochondrial matrix, either by proton cotransport or in exchange for hydroxyl ions. In the final steps of oxidative phosphorylation, this protein catalyzes the uptake of a phosphate ion with a proton across the mitochondrial inner membrane. The availability of inorganic phosphate for oxidative phosphorylation is mainly dependent on PHC activity. To substantially affect oxidative phosphorylation, PHC depletion must be severe, exceeding 85%. This protein may be involved in regulation of the mitochondrial permeability transition pore (mPTP).
# Clinical significance
Mutations in this gene can cause mitochondrial phosphate carrier deficiency (MPCD), a fatal disorder of oxidative phosphorylation. Symptoms include lactic acidosis, hypertrophic cardiomyopathy, and neonatal hypotonia; afflicted patients die within the first year of life.
Isoform A of this gene is expressed at high levels in heart, pancreatic, and skeletal muscle cells while Isoform B is expressed in all tissues, albeit poorly.
In the sole recorded case of a mutation in this gene, a homozygous mutation (c.215G>A) in the alternatively spliced exon 3A of this gene caused an amino acid replacement (G72E) in Isoform A. This leads to ATP synthase deficiency in muscle cells, which express Isoform A, but not in fibroblasts, which express Isoform B, causing MPCD and the aforementioned standard symptoms.
# Interactions
The encoded protein interacts with PPIF; this interaction is impaired by CsA. | SLC25A3
Phosphate carrier protein, mitochondrial is a protein that in humans is encoded by the SLC25A3 gene.[1][2] The encoded protein is a transmembrane protein located in the mitochondrial inner membrane and catalyzes the transport of phosphate ions across it for the purpose of oxidative phosphorylation.[3][4] There are two significant isoforms of this gene expressed in human cells, which differ slightly in structure and function.[5] Mutations in this gene can cause mitochondrial phosphate carrier deficiency (MPCD), a fatal disorder of oxidative phosphorylation symptomized by lactic acidosis, neonatal hypotonia, hypertrophic cardiomyopathy, and death within the first year of life.[3][4]
# Structure
The SLC25A3 gene is located on the q arm of chromosome 12 in position 23.1 and spans 8,376 base pairs.[2] The gene has 9 exons and produces a 40.1 kDa protein composed of 362 amino acids.[6][7][5] The encoded protein (PHC) is a multi-pass transmembrane protein located in the mitochondrial inner membrane; it contains six transmembrane segments, emerging into a large extramembranous loop.[3][4][8] Both the N-terminal and C-terminal regions of this protein protrude toward the cytosol. PHC contains three related segments arranged in tandem which are related to those found in other characterized members of the mitochondrial carrier family.[2] There exist two transcript variants of this protein, PHC-A and PHC-B, which differ by 13 amino acids.[8] Isoform A contains 42 amino acids while Isoform B contains 41. In vitro, the isoforms differ in their substrate affinities and transport rates.[9][5]
# Function
The encoded protein (PHC) catalyzes the transport of phosphate from the cytosol into the mitochondrial matrix, either by proton cotransport or in exchange for hydroxyl ions.[2] In the final steps of oxidative phosphorylation, this protein catalyzes the uptake of a phosphate ion with a proton across the mitochondrial inner membrane.[5] The availability of inorganic phosphate for oxidative phosphorylation is mainly dependent on PHC activity.[9] To substantially affect oxidative phosphorylation, PHC depletion must be severe, exceeding 85%.[10] This protein may be involved in regulation of the mitochondrial permeability transition pore (mPTP).[3][4]
# Clinical significance
Mutations in this gene can cause mitochondrial phosphate carrier deficiency (MPCD), a fatal disorder of oxidative phosphorylation. Symptoms include lactic acidosis, hypertrophic cardiomyopathy, and neonatal hypotonia; afflicted patients die within the first year of life.[3][4]
Isoform A of this gene is expressed at high levels in heart, pancreatic, and skeletal muscle cells while Isoform B is expressed in all tissues, albeit poorly.[9][5]
In the sole recorded case of a mutation in this gene, a homozygous mutation (c.215G>A) in the alternatively spliced exon 3A of this gene caused an amino acid replacement (G72E) in Isoform A. This leads to ATP synthase deficiency in muscle cells, which express Isoform A, but not in fibroblasts, which express Isoform B, causing MPCD and the aforementioned standard symptoms.[11][5]
# Interactions
The encoded protein interacts with PPIF; this interaction is impaired by CsA.[3][4] | https://www.wikidoc.org/index.php/SLC25A3 | |
ba80f6479cb1e5c29e8f6d16f8aefab688b91d96 | wikidoc | SLC25A5 | SLC25A5
Solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 5 is a protein that in humans is encoded by the SLC25A5 gene on the X chromosome.
This protein functions as an antiporter for ADP/ATP exchange between the mitochondrial matrix and cytoplasm. As a result, it plays a key role in maintaining mitochondrial membrane potential and inhibiting apoptosis and has been targeted for treating cancer.
# Structure
The SLC25A5 gene belongs to the ANT gene family, which itself belongs to the superfamily that includes genes encoding brown fat mitochondrial uncoupling proteins and mitochondrial phosphate carrier proteins. Compared to the other gene isoforms, SLC25A5 possesses different motifs, including a CCACT sequence rather than the canonical CCAAT sequence upstream of the TATA box, as well as five SP1 binding sites. This gene consists of 4 exons, while its encoded protein forms a homodimer embedded in the inner mitochondrial membrane. The entire protein is composed of 300-320 amino acid residues folded into six transmembrane helices. The human genome contains four differentially expressed isoforms, as well as several non-transcribed pseudogenes, of this gene.
# Function
This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene, adenine nucleotide translocator 2 (ANT2), functions as a major constituent of the mitochondrial permeability-transition pore complex that catalyzes the exchange of mitochondrial ATP with cytosolic ADP. As a result of its antiporter function, ANT2 maintains mitochondrial membrane potential by regulating ADP/ATP ratios in oxidative phosphorylation. ANT2 facilitates uncoupling of the mitochondrial membrane when acylated by SIRT4. Though uncoupling the membrane potential typically leads to apoptosis, ANT2 was found to be antiapoptotic. As a result, it is postulated to mediate the TFIIH-dependent response to DNA damage as a component of the MMS19-XPD. Alternatively, suppressing the expression of this gene has been shown to induce apoptosis and inhibit tumor growth.
Though ANT2 is highly conserved and ubiquitously expressed, its expression levels and, accordingly, biological function, may vary depending on tissue type. It is specifically expressed in undifferentiated cells and renewable tissues while maintaining low expression levels in differentiated cells. Due to its expression profile, it has been used as a growth marker and targeted for studies in tumor cell growth.
# Clinical Significance
The SLC25A5 enzyme is an important constituent in apoptotic signaling and oxidative stress, most notably as part of the mitochondrial death pathway and cardiac myocyte apoptosis signaling. Programmed cell death is a distinct genetic and biochemical pathway essential to metazoans. An intact death pathway is required for successful embryonic development and the maintenance of normal tissue homeostasis. Apoptosis has proven to be tightly interwoven with other essential cell pathways. The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics 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.
The SLC25A5 gene is important for the coding of the most abundant mitochondrial protein Ancp which represents 10% of the proteins of the inner membrane of bovine heart mitochondria. Ancp is encoded by four different genes: SLC25A4 (also known as ANC1 or ANT1), SLC25A5 (ANC3 or ANT2), SLC25A6 (ANC2 or ANT3) and SLC25A31 (ANC4 or ANT4). Their expression is tissue specific and highly regulated and adapted to particular cellular energetic demand. Indeed, human ANC expression patterns depend on the tissue and cell types, the developmental stage and the status of cell proliferation. Furthermore, expression of the genes is modulated by different transcriptional elements in the promoter regions. Therefore, Ancp emerges as a logical candidate to regulate the cellular dependence on oxidative energy metabolism.
Overexpression of ANT2 has been linked to tumor cell growth and attributed to its anti-apoptotic function. One study found that specific silencing of the ANT2 gene failed to induce apoptosis to tumor cells without a combining treatment with lonidamine, an anti-tumor drug, thus indicating that additional factors may be involved to mediate membrane permeability and programmed cell death. According to a study by Oishi et al., knockdown of ANT2 upregulated DR5, resulting in Apo2L/TRAIL-induced apoptosis. Moreover, studies by Ji-Young Jang et al. confirmed the effectiveness of silencing ANT2 in breast cancer and hepatocellular carcinoma using small hairpin RNAs (shRNA). Thus, ANT2 inhibitors could contribute to anticancer therapies.
In the brain, ANT2 participates as part of the post-synaptic density (PSD) and, thus, has been associated with X-linked intellectual disability (XLID).
# Interactions
SLC25A5 has been shown to interact with:
- SIRT4 | SLC25A5
Solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 5 is a protein that in humans is encoded by the SLC25A5 gene on the X chromosome.[1]
This protein functions as an antiporter for ADP/ATP exchange between the mitochondrial matrix and cytoplasm.[1][2][3] As a result, it plays a key role in maintaining mitochondrial membrane potential and inhibiting apoptosis and has been targeted for treating cancer.[1][2]
# Structure
The SLC25A5 gene belongs to the ANT gene family, which itself belongs to the superfamily that includes genes encoding brown fat mitochondrial uncoupling proteins and mitochondrial phosphate carrier proteins. Compared to the other gene isoforms, SLC25A5 possesses different motifs, including a CCACT sequence rather than the canonical CCAAT sequence upstream of the TATA box, as well as five SP1 binding sites.[4] This gene consists of 4 exons, while its encoded protein forms a homodimer embedded in the inner mitochondrial membrane.[1][2] The entire protein is composed of 300-320 amino acid residues folded into six transmembrane helices.[2][5] The human genome contains four differentially expressed isoforms, as well as several non-transcribed pseudogenes, of this gene.[1][6][7]
# Function
This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene, adenine nucleotide translocator 2 (ANT2), functions as a major constituent of the mitochondrial permeability-transition pore complex that catalyzes the exchange of mitochondrial ATP with cytosolic ADP.[1][5][8] As a result of its antiporter function, ANT2 maintains mitochondrial membrane potential by regulating ADP/ATP ratios in oxidative phosphorylation. ANT2 facilitates uncoupling of the mitochondrial membrane when acylated by SIRT4.[2][3] Though uncoupling the membrane potential typically leads to apoptosis, ANT2 was found to be antiapoptotic. As a result, it is postulated to mediate the TFIIH-dependent response to DNA damage as a component of the MMS19-XPD.[8] Alternatively, suppressing the expression of this gene has been shown to induce apoptosis and inhibit tumor growth.[1][2]
Though ANT2 is highly conserved and ubiquitously expressed, its expression levels and, accordingly, biological function, may vary depending on tissue type.[3][5][7] It is specifically expressed in undifferentiated cells and renewable tissues while maintaining low expression levels in differentiated cells. Due to its expression profile, it has been used as a growth marker and targeted for studies in tumor cell growth.[2][7]
# Clinical Significance
The SLC25A5 enzyme is an important constituent in apoptotic signaling and oxidative stress, most notably as part of the mitochondrial death pathway and cardiac myocyte apoptosis signaling.[9] Programmed cell death is a distinct genetic and biochemical pathway essential to metazoans. An intact death pathway is required for successful embryonic development and the maintenance of normal tissue homeostasis. Apoptosis has proven to be tightly interwoven with other essential cell pathways. The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics 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.[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. 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.
The SLC25A5 gene is important for the coding of the most abundant mitochondrial protein Ancp which represents 10% of the proteins of the inner membrane of bovine heart mitochondria.[11][12] Ancp is encoded by four different genes: SLC25A4 (also known as ANC1 or ANT1), SLC25A5 (ANC3 or ANT2), SLC25A6 (ANC2 or ANT3) and SLC25A31 (ANC4 or ANT4). Their expression is tissue specific and highly regulated and adapted to particular cellular energetic demand. Indeed, human ANC expression patterns depend on the tissue and cell types, the developmental stage and the status of cell proliferation. Furthermore, expression of the genes is modulated by different transcriptional elements in the promoter regions. Therefore, Ancp emerges as a logical candidate to regulate the cellular dependence on oxidative energy metabolism.[11]
Overexpression of ANT2 has been linked to tumor cell growth and attributed to its anti-apoptotic function. One study found that specific silencing of the ANT2 gene failed to induce apoptosis to tumor cells without a combining treatment with lonidamine, an anti-tumor drug, thus indicating that additional factors may be involved to mediate membrane permeability and programmed cell death.[2][6] According to a study by Oishi et al., knockdown of ANT2 upregulated DR5, resulting in Apo2L/TRAIL-induced apoptosis.[6] Moreover, studies by Ji-Young Jang et al. confirmed the effectiveness of silencing ANT2 in breast cancer and hepatocellular carcinoma using small hairpin RNAs (shRNA).[7][13] Thus, ANT2 inhibitors could contribute to anticancer therapies.[6][7]
In the brain, ANT2 participates as part of the post-synaptic density (PSD) and, thus, has been associated with X-linked intellectual disability (XLID).[5]
# Interactions
SLC25A5 has been shown to interact with:
- SIRT4[3] | https://www.wikidoc.org/index.php/SLC25A5 | |
16f6f2a2157c364793ecc3b1339d872c25b5caa9 | wikidoc | SLC26A3 | SLC26A3
Solute carrier family 26, member 3, also known as CLD (chloride anion exchanger), or DRA (downregulated-in-adenoma) is a protein that in humans is encoded by the SLC26A3 gene.
# Function
The downregulated-in-adenoma (DRA) is a membrane protein in intestinal cells. It is an anion exchanger and a member of the sulfate anion transporter (SAT) family. It mediates chloride and bicarbonate exchange and additionally transports sulfate and other anions at the apical membrane, part of the plasma membrane of enterocytes. It is different from the anion exchanger that present in erythrocytes, renal tubule, and several other tissues.
The protein encoded by this gene is a transmembrane glycoprotein that functions as a sulfate transporter. It is localized to the mucosa of the lower intestinal tract, particularly to the apical membrane of columnar epithelium and some goblet cells, and is instrumental in chloride reuptake, aiding in the creation of an osmotic gradient for resorption of fluid from the lumen of the intestine.
# Clinical significance
Mutations in this gene have been associated with congenital chloride diarrhoea, a treatable disease.
The congenital absence of this membrane protein results in an autosomal recessive disorder called congenital chloridorrhea or congenital chloride diarrhea (CLD). | SLC26A3
Solute carrier family 26, member 3, also known as CLD (chloride anion exchanger), or DRA (downregulated-in-adenoma) is a protein that in humans is encoded by the SLC26A3 gene.[1]
# Function
The downregulated-in-adenoma (DRA) is a membrane protein in intestinal cells. It is an anion exchanger and a member of the sulfate anion transporter (SAT) family. It mediates chloride and bicarbonate exchange and additionally transports sulfate and other anions at the apical membrane, part of the plasma membrane of enterocytes. It is different from the anion exchanger that present in erythrocytes, renal tubule, and several other tissues.[2]
The protein encoded by this gene is a transmembrane glycoprotein that functions as a sulfate transporter. It is localized to the mucosa of the lower intestinal tract, particularly to the apical membrane of columnar epithelium and some goblet cells, and is instrumental in chloride reuptake, aiding in the creation of an osmotic gradient for resorption of fluid from the lumen of the intestine.[3]
# Clinical significance
Mutations in this gene have been associated with congenital chloride diarrhoea,[1] a treatable disease.
The congenital absence of this membrane protein results in an autosomal recessive disorder called congenital chloridorrhea or congenital chloride diarrhea (CLD).[4] | https://www.wikidoc.org/index.php/SLC26A3 | |
6da1a8371c3e58225037d7163e45e9b90e709c8c | wikidoc | SLC33A1 | SLC33A1
Acetyl-coenzyme A transporter 1 also known as solute carrier family 33 member 1 (SLC33A1) is a protein that in humans is encoded by the SLC33A1 gene.
# Function
The protein encoded by this gene is required for the formation of O-acetylated (Ac) gangliosides. The encoded protein is predicted to contain 6 to 10 transmembrane domains, and a leucine zipper motif in transmembrane domain III.
# Clinical significance
Defects in this gene have been reported to cause spastic paraplegia autosomal dominant type 42 (SPG42) in one Chinese family, but not in similar patients of European descent. | SLC33A1
Acetyl-coenzyme A transporter 1 also known as solute carrier family 33 member 1 (SLC33A1) is a protein that in humans is encoded by the SLC33A1 gene.[1]
# Function
The protein encoded by this gene is required for the formation of O-acetylated (Ac) gangliosides. The encoded protein is predicted to contain 6 to 10 transmembrane domains, and a leucine zipper motif in transmembrane domain III.[1]
# Clinical significance
Defects in this gene have been reported to cause spastic paraplegia autosomal dominant type 42 (SPG42) in one Chinese family, but not in similar patients of European descent.[1] | https://www.wikidoc.org/index.php/SLC33A1 | |
481fff5c7124f2699244a677e8b52c93d2d6deb3 | wikidoc | SLC34A3 | SLC34A3
Sodium-dependent phosphate transport protein 2C is a protein that in humans is encoded by the SLC34A3 gene.
# Function
SLC34A3 contributes to the maintenance of inorganic phosphate concentration at the kidney.
# Interactions
SLC34A3 has been shown to interact with PDZK1.
# Clinical Correlation
A mutation in the SLC34A3 gene has been known to cause the autosomal recessive condition hereditary hypophophatemic rickets with hypercalciuria. This gene is correlated closely with SLC34A1, an analogue sodium phosphate cotransporter protein. Symptoms include renal phosphate wasting in addition to increase levels of 1,25-dihydroxyvitamin D (yields the hypercalcuria). | SLC34A3
Sodium-dependent phosphate transport protein 2C is a protein that in humans is encoded by the SLC34A3 gene.[1][2][3][4]
# Function
SLC34A3 contributes to the maintenance of inorganic phosphate concentration at the kidney.[4]
# Interactions
SLC34A3 has been shown to interact with PDZK1.[5]
# Clinical Correlation
A mutation in the SLC34A3 gene has been known to cause the autosomal recessive condition hereditary hypophophatemic rickets with hypercalciuria. This gene is correlated closely with SLC34A1, an analogue sodium phosphate cotransporter protein. Symptoms include renal phosphate wasting in addition to increase levels of 1,25-dihydroxyvitamin D (yields the hypercalcuria).[2] | https://www.wikidoc.org/index.php/SLC34A3 | |
cabf745ff6715452ea26cd7ab7cd19cc8a76f05f | wikidoc | SLC35F6 | SLC35F6
SLC35F6 is a protein that in humans is encoded by the SLC35F6 gene. The orthologue in mice is 4930471M23Rik.
# Model organisms
Model organisms have been used in the study of C2orf18 function. A conditional knockout mouse line, called 4930471M23Riktm1a(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 — at the Wellcome Trust Sanger Institute.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty two tests were carried out on mutant mice, but no significant abnormalities were observed. | SLC35F6
SLC35F6 is a protein that in humans is encoded by the SLC35F6 gene.[1][2] The orthologue in mice is 4930471M23Rik.[2]
# Model organisms
Model organisms have been used in the study of C2orf18 function. A conditional knockout mouse line, called 4930471M23Riktm1a(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 — at the Wellcome Trust Sanger Institute.[9][10][11]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty two tests were carried out on mutant mice, but no significant abnormalities were observed.[5] | https://www.wikidoc.org/index.php/SLC35F6 | |
06d43d82583c15edb423a11402db0ccf0c9ccb7a | wikidoc | SLC39A7 | SLC39A7
Zinc transporter SLC39A7 (ZIP7) also known as solute carrier family 39 member 7 (SLC39A7) is a protein that in humans is encoded by the SLC39A7 gene.
# Function
Zinc is an essential cofactor for more than 50 classes of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. Zinc cannot passively diffuse across cell membranes and requires specific transporters, such as SLC39A7, to enter the cytosol from both the extracellular environment and from intracellular storage compartments.
ZIP7 is a membrane transport protein of the endoplasmic reticulum. Phosphorylation of ZIP7 by casein kinase 2 stimulates the release of zinc ions from the endoplasmic reticulum This provides a signal transduction pathway by which activation of cell surface receptors such as the epidermal growth factor receptor can regulate the activity of downstream phosphatases and kinases. | SLC39A7
Zinc transporter SLC39A7 (ZIP7) also known as solute carrier family 39 member 7 (SLC39A7) is a protein that in humans is encoded by the SLC39A7 gene.[1][2][3]
# Function
Zinc is an essential cofactor for more than 50 classes of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. Zinc cannot passively diffuse across cell membranes and requires specific transporters, such as SLC39A7, to enter the cytosol from both the extracellular environment and from intracellular storage compartments.[3]
ZIP7 is a membrane transport protein of the endoplasmic reticulum.[4] Phosphorylation of ZIP7 by casein kinase 2 stimulates the release of zinc ions from the endoplasmic reticulum[5] This provides a signal transduction pathway by which activation of cell surface receptors such as the epidermal growth factor receptor can regulate the activity of downstream phosphatases and kinases. | https://www.wikidoc.org/index.php/SLC39A7 | |
63767d8324244c534ecd4d17d089798eb2543cb3 | wikidoc | SLC41A3 | SLC41A3
Solute carrier family 41, member 3 is a protein that in humans is encoded by the SLC41A3 gene.
# Model organisms
Model organisms have been used in the study of SLC41A3 function. A conditional knockout mouse line, called Slc41a3tm1a(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 one significant abnormality was observed: homozygous mutants displayed abnormal locomotor coordination. | SLC41A3
Solute carrier family 41, member 3 is a protein that in humans is encoded by the SLC41A3 gene.[1]
# Model organisms
Model organisms have been used in the study of SLC41A3 function. A conditional knockout mouse line, called Slc41a3tm1a(KOMP)Wtsi[6][7] 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.[8][9][10]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[4][11] Twenty six tests were carried out on mutant mice and one significant abnormality was observed: homozygous mutants displayed abnormal locomotor coordination.[4] | https://www.wikidoc.org/index.php/SLC41A3 | |
8c574f03cc10dbb74cc811a0da90d90b0283bb7b | wikidoc | SLC45A2 | SLC45A2
Membrane-associated transporter protein (MATP) also known as solute carrier family 45 member 2 (SLC45A2) or melanoma antigen AIM1 is a protein that in humans is encoded by the SLC45A2 gene.
# Function
SLC45A2 is a transporter protein that mediates melanin synthesis. SLC45A2 is also a melanocyte differentiation antigen that is expressed in a high percentage of melanoma cell lines. A similar sequence gene in medaka fish, 'B,' encodes a transporter that mediates melanin synthesis. Mutations in this gene are a cause of oculocutaneous albinism type 4. Alternative splicing results in multiple transcript variants encoding different isoforms.
In melanocytic cell types, the SLC45A2 gene is regulated by microphthalmia-associated transcription factor.
SLC45A2 has been found to play a role in pigmentation in several species. In humans, it has been identified as a factor in the light skin of Europeans and as an ancestry-informative marker (AIM) for distinguishing Sri Lankan from European ancestry. SLC45A2 is the so-called cream gene responsible in horses for buckskin, palomino and cremello coloration, while a mutation in this gene underlies the white tiger variant. SLC45A2 was identified as a melanoma tumor-associated antigen with high tumor specificity and reduced potential for autoimmune toxicity, and is currently in clinical development as a target for T-cell based immunotherapy. | SLC45A2
Membrane-associated transporter protein (MATP) also known as solute carrier family 45 member 2 (SLC45A2) or melanoma antigen AIM1 is a protein that in humans is encoded by the SLC45A2 gene.[1][2][3]
# Function
SLC45A2 is a transporter protein that mediates melanin synthesis. SLC45A2 is also a melanocyte differentiation antigen that is expressed in a high percentage of melanoma cell lines.[4] A similar sequence gene in medaka fish, 'B,' encodes a transporter that mediates melanin synthesis. Mutations in this gene are a cause of oculocutaneous albinism type 4. Alternative splicing results in multiple transcript variants encoding different isoforms.[3]
In melanocytic cell types, the SLC45A2 gene is regulated by microphthalmia-associated transcription factor.[5][6]
SLC45A2 has been found to play a role in pigmentation in several species. In humans, it has been identified as a factor in the light skin of Europeans and as an ancestry-informative marker (AIM) for distinguishing Sri Lankan from European ancestry.[7] SLC45A2 is the so-called cream gene responsible in horses for buckskin, palomino and cremello coloration, while a mutation in this gene underlies the white tiger variant.[8] SLC45A2 was identified as a melanoma tumor-associated antigen with high tumor specificity and reduced potential for autoimmune toxicity, and is currently in clinical development as a target for T-cell based immunotherapy.[9] | https://www.wikidoc.org/index.php/SLC45A2 | |
f53236ced46a6c97c3c9865c086f1bd759452e21 | wikidoc | SLC45A3 | SLC45A3
Solute carrier family 45 member 3 (SLC45A3), also known as prostate cancer-associated protein 6 or prostein, is a protein that in humans is encoded by the SLC45A3 gene.
SLC45A3 is expressed in a prostate-specific manner by normal tissues and at a significantly lower level in prostate tumor cell lines. Treatment prostate cancer cell lines with androgens upregulates the expression of SLC45A3.
# Regulation
There is evidence that the expression of SLC45A3 is regulated by the microRNA mir-126*. | SLC45A3
Solute carrier family 45 member 3 (SLC45A3), also known as prostate cancer-associated protein 6 or prostein, is a protein that in humans is encoded by the SLC45A3 gene.[1][2][3]
SLC45A3 is expressed in a prostate-specific manner by normal tissues and at a significantly lower level in prostate tumor cell lines. Treatment prostate cancer cell lines with androgens upregulates the expression of SLC45A3.[3]
# Regulation
There is evidence that the expression of SLC45A3 is regulated by the microRNA mir-126*.[4] | https://www.wikidoc.org/index.php/SLC45A3 | |
7a94535e515eefab16d34f26fe738b19ebb73bd4 | wikidoc | SLC47A1 | SLC47A1
Multidrug and toxin extrusion protein 1 (MATE1), also known as solute carrier family 47, member 1, is a protein that in humans is encoded by the SLC47A1 gene. SLC47A1 belongs to the MATE (multidrug and toxic compound extrusion) family of transporters that are found in bacteria, archaea and eukaryotes.
# Gene
The SLC47A1 gene is located within the Smith-Magenis syndrome region on chromosome 17.
# Function
SLC47A1 is a member of the MATE family of transporters that excrete endogenous and exogenous toxic electrolytes through urine and bile.
# Discovery
The multidrug efflux transporter NorM from V. parahaemolyticus which mediates resistance to multiple antimicrobial agents (norfloxacin, kanamycin, ethidium bromide etc.) and its homologue from E. coli were identified in 1998, which is the first of Solute carrier family 47 member. NorM seems to function as drug/sodium antiporter which is the first example of Na+-coupled multidrug efflux transporter. NorM is a prototype of a new transporter family and Brown et al. named it the multidrug and toxic compound extrusion family. The X-ray structure of the transporter NorM was determined to 3.65 Å, revealing an outward-facing conformation with two portals open to the outer leaflet of the membrane and a unique topology of the predicted 12 transmembrane helices distinct from any other known multidrug resistance transporter. | SLC47A1
Multidrug and toxin extrusion protein 1 (MATE1), also known as solute carrier family 47, member 1, is a protein that in humans is encoded by the SLC47A1 gene.[1][2] SLC47A1 belongs to the MATE (multidrug and toxic compound extrusion) family of transporters that are found in bacteria, archaea and eukaryotes.[3][4]
# Gene
The SLC47A1 gene is located within the Smith-Magenis syndrome region on chromosome 17.[1]
# Function
SLC47A1 is a member of the MATE family of transporters that excrete endogenous and exogenous toxic electrolytes through urine and bile.[2]
# Discovery
The multidrug efflux transporter NorM from V. parahaemolyticus which mediates resistance to multiple antimicrobial agents (norfloxacin, kanamycin, ethidium bromide etc.) and its homologue from E. coli were identified in 1998, which is the first of Solute carrier family 47 member.[3] NorM seems to function as drug/sodium antiporter which is the first example of Na+-coupled multidrug efflux transporter.[5] NorM is a prototype of a new transporter family and Brown et al. named it the multidrug and toxic compound extrusion family.[4] The X-ray structure of the transporter NorM was determined to 3.65 Å, revealing an outward-facing conformation with two portals open to the outer leaflet of the membrane and a unique topology of the predicted 12 transmembrane helices distinct from any other known multidrug resistance transporter.[6] | https://www.wikidoc.org/index.php/SLC47A1 | |
d90536700dcea92b797bb718c8db37e2f1102357 | wikidoc | SLC47A2 | SLC47A2
Solute carrier family 47, member 2, also known as SLC47A2, is a protein which in humans is encoded by the SLC47A2 gene.
# Function
This gene encodes a protein belonging to a family of transporters involved in excretion of toxic electrolytes, both endogenous and exogenous, through urine and bile. This transporter family shares homology with the bacterial MATE (multi antimicrobial extrusion protein or multidrug and toxic compound extrusion) protein family responsible for drug resistance. This gene is one of two members of the MATE transporter family located near each other on chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene.
# Discovery
The multidrug efflux transporter NorM from V. parahaemolyticus which mediates resistance to multiple antimicrobial agents (norfloxacin, kanamycin, ethidium bromide etc.) and its homologue from E. coli were identified in 1998. NorM seems to function as drug/sodium antiporter which is the first example of Na+-coupled multidrug efflux transporter discovered. NorM is a prototype of a new transporter family and Brown et al. named it the multidrug and toxic compound extrusion family. The X-ray structure of the NorM was determined to 3.65 Å, revealing an outward-facing conformation with two portals open to the outer leaflet of the membrane and a unique topology of the predicted 12 transmembrane helices distinct from any other known multidrug resistance transporter. | SLC47A2
Solute carrier family 47, member 2, also known as SLC47A2, is a protein which in humans is encoded by the SLC47A2 gene.[1]
# Function
This gene encodes a protein belonging to a family of transporters involved in excretion of toxic electrolytes, both endogenous and exogenous, through urine and bile. This transporter family shares homology with the bacterial MATE (multi antimicrobial extrusion protein or multidrug and toxic compound extrusion) protein family responsible for drug resistance.[2] This gene is one of two members of the MATE transporter family located near each other on chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene.[1]
# Discovery
The multidrug efflux transporter NorM from V. parahaemolyticus which mediates resistance to multiple antimicrobial agents (norfloxacin, kanamycin, ethidium bromide etc.) and its homologue from E. coli were identified in 1998.[2] NorM seems to function as drug/sodium antiporter which is the first example of Na+-coupled multidrug efflux transporter discovered.[3] NorM is a prototype of a new transporter family and Brown et al. named it the multidrug and toxic compound extrusion family.[4] The X-ray structure of the NorM was determined to 3.65 Å, revealing an outward-facing conformation with two portals open to the outer leaflet of the membrane and a unique topology of the predicted 12 transmembrane helices distinct from any other known multidrug resistance transporter.[5] | https://www.wikidoc.org/index.php/SLC47A2 | |
0b277ead18fa44b0dd018b57af2d9f8f8c00e79e | wikidoc | SLC52A3 | SLC52A3
Solute carrier family 52 (riboflavin transporter), member 3, formerly known as chromosome 20 open reading frame 54 and riboflavin transporter 2, is a protein that in humans is encoded by the SLC52A3 gene.
# Function
This locus likely encodes a transmembrane protein that may function as a riboflavin transporter.
# Clinical significance
Mutations at this locus have been associated with Fazio–Londe disease and Brown-Vialetto-Van Laere syndrome.
# Model organisms
Model organisms have been used in the study of C20orf54 function. The orthologous gene in mice is called 2310046K01Rik. A conditional knockout mouse line, called 2310046K01Riktm2a(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 five tests were carried out on mutant mice and three significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and males had an increased mean corpuscular haemoglobin concentration. | SLC52A3
Solute carrier family 52 (riboflavin transporter), member 3, formerly known as chromosome 20 open reading frame 54 and riboflavin transporter 2, is a protein that in humans is encoded by the SLC52A3 gene.[1][2]
# Function
This locus likely encodes a transmembrane protein that may function as a riboflavin transporter.[1][2]
# Clinical significance
Mutations at this locus have been associated with Fazio–Londe disease and Brown-Vialetto-Van Laere syndrome.[3][4]
# Model organisms
Model organisms have been used in the study of C20orf54 function. The orthologous gene in mice is called 2310046K01Rik. A conditional knockout mouse line, called 2310046K01Riktm2a(KOMP)Wtsi[11][12] 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.[13][14][15]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty five tests were carried out on mutant mice and three significant abnormalities were observed.[9] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and males had an increased mean corpuscular haemoglobin concentration.[9] | https://www.wikidoc.org/index.php/SLC52A3 | |
dae0c5e5c91366e6c59c8a1532928ad43d8509af | wikidoc | SLC6A15 | SLC6A15
Solute carrier family 6 member 15 (SLC6A15) also known as the sodium-dependent neutral amino acid transporter B(0)AT2 (B0AT2)' is a protein that in humans is encoded by the SLC6A15 gene.
# Function
SLC6A15 shows structural characteristics of an Na+ and Cl−-dependent neurotransmitter transporter, including 12 transmembrane (TM) domains, intracellular N and C termini, and large extracellular loops containing multiple N-glycosylation sites.
# Clinical relevance
Variants of this gene linked with depression are associated with reduced SLC6A15 expression in the human hippocampus, as well as decreased volume of this brain region. | SLC6A15
Solute carrier family 6 member 15 (SLC6A15) also known as the sodium-dependent neutral amino acid transporter B(0)AT2 (B0AT2)' is a protein that in humans is encoded by the SLC6A15 gene.[1]
# Function
SLC6A15 shows structural characteristics of an Na+ and Cl−-dependent neurotransmitter transporter, including 12 transmembrane (TM) domains, intracellular N and C termini, and large extracellular loops containing multiple N-glycosylation sites.[2]
# Clinical relevance
Variants of this gene linked with depression are associated with reduced SLC6A15 expression in the human hippocampus, as well as decreased volume of this brain region.[3] | https://www.wikidoc.org/index.php/SLC6A15 | |
39f741763b855fb1e3c695bc1059839cf16f02e6 | wikidoc | SLC7A11 | SLC7A11
Cystine/glutamate transporter is an antiporter that in humans is encoded by the SLC7A11 gene.
The SLC7A11 gene codes for a sodium-independent cystine-glutamate antiporter that is chloride dependent, known as system Xc- or xCT. It regulates synaptic activity by stimulating extrasynaptic receptors and performs nonvesicular glutamate release. This gene is highly expressed by astrocytes and couples the uptake of one molecule of cystine with the release of one molecule of glutamate. The dimer cystine gets taken up by glial cells and the monomer of cystine, cysteine, is taken up by neurons. The expression of Xc- was detected throughout the brain with higher expression found in the basolateral amygdala and the prefrontal cortex. The inhibition of system Xc- has been found to alter a number of behaviors, which suggests that it plays a key role in excitatory signaling.
# Structure
SLC7A11 is a member of a heterodimeric Na+-independent anionic amino acid transport system highly specific for cystine and glutamate. This antiporter imports cystine and exports glutamate, which are both amino acids. An antiporter functions with a one-to-one counter-transport, which is when one substance is transported across the membrane at the same time another substance is transported across the membrane in the opposite direction. The antiporter is a heterodimeric amino acid transporter. The structure of this protein includes two chains: a specific light chain, xCT, and a heavy chain, 4F2, which are linked by a disulfide bridge. The xCT chain has 12 transmembrane domains consisting of 501 amino acids, and the 4F2 chain appears to be highly conserved among transporters. The human xCT has an 89% similarity of amino acids to a mouse xCT. The complementary DNA, cDNA, has a total of 9648 base pairs. The SLC7A11 gene has been found not only in the brain, but has also been found to be expressed in the spinal cord, pancreas, and in glioma cells.
# Regulation
There are many mechanisms that exist to regulate the expression of system Xc-, although it is not the sole determinate of extracellular glutamate or intracellular glutathione. An example is amino acid deprivation, which triggers up regulation of the transporter. A key regulator is extracellular glutamate; when it becomes excessive, it goes from an excitatory transmitter to an excitotoxin. The inhibition of uptake of extracellular glutamate leads to oxidative glutamate toxicity or ferroptosis. This regulation may be done through Excitatory Amino Acid Transporters (EAATs), which decrease extracellular glutamate and increase intracellular glutamate in astrocytes. When looking at its structure, xCT seems to be the main determinant for the system's activity. Glutamate and cystine can be transported in both directions, but, generally, more cystine is imported and more glutamate is exported. Extracellular glutamate acts as a competitive inhibitor for cystine uptake via system Xc-.
## Glutamate
There is a copious amount of glutamate in mammalian cells. Glutamate is necessary for excitatory signaling between neurons. The release must be highly organized, due to the large amounts of glutamate at the synaptic cleft, and the fact that it is released at high speeds. This mechanism of release at the synaptic cleft is partially controlled through the active transport of glutamate out of astrocytes by system Xc-. This release also has a physiological role in the regulation of glutamate metabotropic receptors and control of other neurotransmitters.
## Cystine
Cystine is a dimer consisting of two cysteine molecules and the formation of a disulfide bond. This amino acid is a rate limiting substrate used in the SLC7A11 cystine/glutamate transporter and is usually imported into the cell. Cysteine-158 is specifically used in the formation of the disulfide bridge for the protein structure of system Xc-. There are neurotoxins, such as BMAA, that can prevent the intake of cystine, which can lead to decreased extracellular glutamate levels and an increase in oxidative stress.
## Pharmacological Inhibition
System Xc- can be inhibited by many small molecules. Excess amounts of the endogenous substrate glutamate inhibits the function of system Xc-. Synthetic small molecules such as erastin, sulfasalazine, and sorafenib can inhibit system Xc- function and induce ferroptosis.
# Clinical applications
Many central nervous system (CNS) disorders are due to a dysfunction in glutamate signaling. Glutamate is transported via EAATs and system Xc-. If either of these transporters are impaired, it could result in a disruption in glutamate homeostasis and lead to a variety of CNS disorders
## Drug addiction
It has been found that cocaine produces a decrease in Cystine-Glutamate exchange via system Xc-, leading to a decrease in basal, extra synaptic glutamate levels in the nucleus accumbens core (NAcc) region of the brains of cocaine-withdrawn rats. It has also been observed in withdrawn rats that a decrease in Group 2 mGluR inhibition of vesicular release, most likely due to the decrease in extrasynaptic glutamate levels, leads to an increase in cocaine-evoked glutamate signaling in their NAcc. An infusion of cysteine in the NAcc of withdrawn rats leads to an increase in extrasynaptic glutamate, near the levels of the control rats, and prevents an increase in synaptic glutamate signaling after a cocaine injection. These findings suggest there is a decrease in system Xc- activity in cocaine-withdrawn rats. It has also been found that cocaine increases glutamate signaling in the synaptic cleft, further supporting this conclusion.
Administration of the cysteine prodrugs N-acetylcysteine or L-2-oxothiazolidine-4-carboxylate blocks cocaine reinstatement in rats. N-acetylcysteine has been shown to decrease drug-seeking behavior for nicotine and heroin as well. However, N-acetylcysteine does not alter the cocaine-induced rush or euphoria; it only causes a reduction in drug-seeking behavior. N-acetylcysteine works by increasing levels of cysteine in cells, leading to an increase in system Xc- activity. This increase in system Xc- activity leads to an increase in extrasynaptic glutamate, causing stimulation of Group 2 mGluRs and an inhibition of synaptic release of glutamate. Cysteine prodrugs also lead to an increase in antioxidant properties by increasing levels of glutathione. Increased levels of glutathione lead to a lower toxicity of methamphetamine and alcohol, and cause a decrease in tumor formation after chronic smoking. N-acetylcysteine has been shown to decrease cravings and use of cocaine and tobacco, as well as other compulsive behaviors such as gambling and trichotillomania.
Repeated administration of cocaine causes disruptions in glutamate homeostasis that lead to a decrease in function of EAATs. It is also possible that glutamate is diffusing from surrounding synapses and is stimulating extrasynaptic receptors. All of these factors may be leading to the disruptions in glutamate signaling that are associated with drug addiction.
## Schizophrenia
It has been proposed that schizophrenia may be due to an increase or a decrease in glutamate signaling, leading to abnormal excitatory signaling in the prefrontal cortex region of the brain. Glutamate release by astrocytes has been linked to the synchrony of neurons in the hippocampus and cortex. A decrease in system Xc- activity may result in an increase in synaptic glutamate and a decrease in extrasynaptic glutamate. Administration of N-acetylcysteine leads to an increase in extrasynaptic NMDA receptor activation, suggesting that glutamate released from system Xc- may cause the activation of extrasynaptic NMDA receptors. A decrease in system Xc- activity may cause a decrease in the activation of extrasynaptic NMDA receptors due to either a decrease in extrasynaptic Glutamate levels or a decrease in glutathione levels after the decrease in cystine transport. On the other hand, a decrease in system Xc- activity may lead to an increase in the activation of synaptic NMDA receptors due to the decrease in activation of Group 2 mGluRs. A decrease in nonvesicular release of glutamate leads to an increase in expression of postsynaptic glutamate receptors, such as NMDA receptors. A disruption in nonvesicular glutamate release may affect synapse formation, lead to altered release of neurotransmitters, and could even disturb cortical migration during development. All of these seem to be associated with schizophrenia.
An increase in the expression of Group 2 mGluRs, which could arise from a chronic under stimulation of these receptors, has been associated with schizophrenia. An increase in levels of system Xc- has also been found in postmortem schizophrenia patients, indicating that there may have been a decrease in net function of these receptors as well, leading to greater expression. It has been observed that Schizophrenia patients have a decreased level of glutathione in their prefrontal cortex, further supporting the conclusion that system Xc- may not be functioning properly.
Clinical trials have shown therapeutic potential for N-acetylcysteine in treating schizophrenia. Again, changes in EAATs due to disruptions in Glutamate homeostasis may also be involved.
Recent study showed that mRNA expression levels of both SLC3A2 and SLC7A11 in WBCs of schizophrenia patients are lower than that of healthy individuals. The finding supports the hypo-glutamatergic neurotransmission hypothesis in schizophrenia.
## Neurodegenerative disorders
The release of glutamate by system Xc- may lead to excitotoxicity, which is initiated by extrasynaptic NMDA receptors and can cause neuronal death. It has been observed that glutamate released from microglia leads to oligodendrocyte death in culture and in the rat optic nerve. However, an increase in system Xc- activity also has a protective effect by increasing levels of glutathione. Oxidative stress has been shown to lead to an increase in system Xc- expression, therefore there must be a balance between the positive protective effects of increased glutathione levels and the negative excitotoxicity effects of increased extrasynaptic glutamate levels.
### Gliomas
A glioma is essentially a glial-derived tumor. These can be induced by an increase in glutamate levels due to an increase in system Xc- activity. Using inhibitors of system Xc- as a treatment for gliomas is currently under active investigation.
### Amyotrophic lateral sclerosis
It has been shown that amyotrophic lateral sclerosis (ALS) is clearly linked to changes in glutamate signaling and glutathione levels; there is also an astrocytic component linked to the disease. All of these factors suggest that a dysfunction in system Xc- may contribute to ALS. It has been observed that an increase in the expression of Nrf2, a transcription factor for system Xc-, leads to a protective effect in mice with ALS symptoms.
### Alzheimer's
There is indirect evidence to suggest that system Xc- might be upregulated in Alzheimer's patients. It has been found in Alzheimer's patients that there is an increase in phosphorylation of the alpha subunit of eukaryotic initiation factor 2 and in expression of transcription factor 4, both of which increase system Xc- expression. It has also been shown that administration of N-acetylcysteine leads to a significant improvement in certain cognitive tasks for Alzheimer's patients.
### Parkinson's disease
Parkinson's disease may be due to mitochondrial dysfunction or oxidative stress, both of which could be caused by a decrease in glutathione levels. Administration of N-acetylcysteine has been shown to counter age-related damage to mitochondria. The therapeutic effects of N-acetylcysteine in the treatment of Parkinson's disease has not been examined yet, though there is a clinical trial that is currently ongoing.
## Neurotoxins
There is evidence that system Xc- may serve as an entry point for neurotoxins and viruses. β-N-methyl-L-alanine (BMAA) is an environmental neurotoxin that can act on system Xc- and inhibit cystine uptake. This leads to a decrease in glutathione levels and an increase in oxidative stress. BMAA can also be transported by system Xc- and lead to an increase in glutamate release and an increase in excitotoxicity. Therefore, BMAA prevents the positive effects of cystine uptake and creates the negative effects of increasing glutamate release. | SLC7A11
Cystine/glutamate transporter is an antiporter that in humans is encoded by the SLC7A11 gene.[1][2][3]
The SLC7A11 gene codes for a sodium-independent cystine-glutamate antiporter that is chloride dependent, known as system Xc- or xCT. It regulates synaptic activity by stimulating extrasynaptic receptors and performs nonvesicular glutamate release. This gene is highly expressed by astrocytes and couples the uptake of one molecule of cystine with the release of one molecule of glutamate. The dimer cystine gets taken up by glial cells and the monomer of cystine, cysteine, is taken up by neurons.[citation needed] The expression of Xc- was detected throughout the brain with higher expression found in the basolateral amygdala and the prefrontal cortex. The inhibition of system Xc- has been found to alter a number of behaviors, which suggests that it plays a key role in excitatory signaling.
# Structure
SLC7A11 is a member of a heterodimeric Na+-independent anionic amino acid transport system highly specific for cystine and glutamate. This antiporter imports cystine and exports glutamate, which are both amino acids. An antiporter functions with a one-to-one counter-transport, which is when one substance is transported across the membrane at the same time another substance is transported across the membrane in the opposite direction. The antiporter is a heterodimeric amino acid transporter.[4] The structure of this protein includes two chains: a specific light chain, xCT, and a heavy chain, 4F2, which are linked by a disulfide bridge.[5] The xCT chain has 12 transmembrane domains consisting of 501 amino acids, and the 4F2 chain appears to be highly conserved among transporters. The human xCT has an 89% similarity of amino acids to a mouse xCT. The complementary DNA, cDNA, has a total of 9648 base pairs. The SLC7A11 gene has been found not only in the brain, but has also been found to be expressed in the spinal cord, pancreas, and in glioma cells.[6][7]
# Regulation
There are many mechanisms that exist to regulate the expression of system Xc-, although it is not the sole determinate of extracellular glutamate or intracellular glutathione. An example is amino acid deprivation, which triggers up regulation of the transporter. A key regulator is extracellular glutamate; when it becomes excessive, it goes from an excitatory transmitter to an excitotoxin.[6] The inhibition of uptake of extracellular glutamate leads to oxidative glutamate toxicity or ferroptosis.[8][9] This regulation may be done through Excitatory Amino Acid Transporters (EAATs), which decrease extracellular glutamate and increase intracellular glutamate in astrocytes. When looking at its structure, xCT seems to be the main determinant for the system's activity. Glutamate and cystine can be transported in both directions, but, generally, more cystine is imported and more glutamate is exported. Extracellular glutamate acts as a competitive inhibitor for cystine uptake via system Xc-.
## Glutamate
There is a copious amount of glutamate in mammalian cells. Glutamate is necessary for excitatory signaling between neurons. The release must be highly organized, due to the large amounts of glutamate at the synaptic cleft, and the fact that it is released at high speeds. This mechanism of release at the synaptic cleft is partially controlled through the active transport of glutamate out of astrocytes by system Xc-. This release also has a physiological role in the regulation of glutamate metabotropic receptors and control of other neurotransmitters.[7]
## Cystine
Cystine is a dimer consisting of two cysteine molecules and the formation of a disulfide bond. This amino acid is a rate limiting substrate used in the SLC7A11 cystine/glutamate transporter and is usually imported into the cell. Cysteine-158 is specifically used in the formation of the disulfide bridge for the protein structure of system Xc-.[6] There are neurotoxins, such as BMAA, that can prevent the intake of cystine, which can lead to decreased extracellular glutamate levels and an increase in oxidative stress.[7]
## Pharmacological Inhibition
System Xc- can be inhibited by many small molecules. Excess amounts of the endogenous substrate glutamate inhibits the function of system Xc-. Synthetic small molecules such as erastin, sulfasalazine, and sorafenib can inhibit system Xc- function and induce ferroptosis.[8]
# Clinical applications
Many central nervous system (CNS) disorders are due to a dysfunction in glutamate signaling. Glutamate is transported via EAATs and system Xc-. If either of these transporters are impaired, it could result in a disruption in glutamate homeostasis and lead to a variety of CNS disorders[10]
## Drug addiction
It has been found that cocaine produces a decrease in Cystine-Glutamate exchange via system Xc-, leading to a decrease in basal, extra synaptic glutamate levels in the nucleus accumbens core (NAcc) region of the brains of cocaine-withdrawn rats. It has also been observed in withdrawn rats that a decrease in Group 2 mGluR inhibition of vesicular release, most likely due to the decrease in extrasynaptic glutamate levels, leads to an increase in cocaine-evoked glutamate signaling in their NAcc.[10] An infusion of cysteine in the NAcc of withdrawn rats leads to an increase in extrasynaptic glutamate, near the levels of the control rats, and prevents an increase in synaptic glutamate signaling after a cocaine injection. These findings suggest there is a decrease in system Xc- activity in cocaine-withdrawn rats. It has also been found that cocaine increases glutamate signaling in the synaptic cleft, further supporting this conclusion.[10]
Administration of the cysteine prodrugs N-acetylcysteine or L-2-oxothiazolidine-4-carboxylate blocks cocaine reinstatement in rats.[10] N-acetylcysteine has been shown to decrease drug-seeking behavior for nicotine and heroin as well. However, N-acetylcysteine does not alter the cocaine-induced rush or euphoria; it only causes a reduction in drug-seeking behavior. N-acetylcysteine works by increasing levels of cysteine in cells, leading to an increase in system Xc- activity. This increase in system Xc- activity leads to an increase in extrasynaptic glutamate, causing stimulation of Group 2 mGluRs and an inhibition of synaptic release of glutamate. Cysteine prodrugs also lead to an increase in antioxidant properties by increasing levels of glutathione. Increased levels of glutathione lead to a lower toxicity of methamphetamine and alcohol, and cause a decrease in tumor formation after chronic smoking.[10] N-acetylcysteine has been shown to decrease cravings and use of cocaine and tobacco, as well as other compulsive behaviors such as gambling and trichotillomania.[10]
Repeated administration of cocaine causes disruptions in glutamate homeostasis that lead to a decrease in function of EAATs. It is also possible that glutamate is diffusing from surrounding synapses and is stimulating extrasynaptic receptors. All of these factors may be leading to the disruptions in glutamate signaling that are associated with drug addiction.
## Schizophrenia
It has been proposed that schizophrenia may be due to an increase or a decrease in glutamate signaling, leading to abnormal excitatory signaling in the prefrontal cortex region of the brain.[10] Glutamate release by astrocytes has been linked to the synchrony of neurons in the hippocampus and cortex. A decrease in system Xc- activity may result in an increase in synaptic glutamate and a decrease in extrasynaptic glutamate. Administration of N-acetylcysteine leads to an increase in extrasynaptic NMDA receptor activation, suggesting that glutamate released from system Xc- may cause the activation of extrasynaptic NMDA receptors. A decrease in system Xc- activity may cause a decrease in the activation of extrasynaptic NMDA receptors due to either a decrease in extrasynaptic Glutamate levels or a decrease in glutathione levels after the decrease in cystine transport. On the other hand, a decrease in system Xc- activity may lead to an increase in the activation of synaptic NMDA receptors due to the decrease in activation of Group 2 mGluRs. A decrease in nonvesicular release of glutamate leads to an increase in expression of postsynaptic glutamate receptors, such as NMDA receptors. A disruption in nonvesicular glutamate release may affect synapse formation, lead to altered release of neurotransmitters, and could even disturb cortical migration during development. All of these seem to be associated with schizophrenia.[10]
An increase in the expression of Group 2 mGluRs, which could arise from a chronic under stimulation of these receptors, has been associated with schizophrenia. An increase in levels of system Xc- has also been found in postmortem schizophrenia patients, indicating that there may have been a decrease in net function of these receptors as well, leading to greater expression. It has been observed that Schizophrenia patients have a decreased level of glutathione in their prefrontal cortex, further supporting the conclusion that system Xc- may not be functioning properly.
Clinical trials have shown therapeutic potential for N-acetylcysteine in treating schizophrenia. Again, changes in EAATs due to disruptions in Glutamate homeostasis may also be involved.
Recent study showed that mRNA expression levels of both SLC3A2 and SLC7A11 in WBCs of schizophrenia patients are lower than that of healthy individuals. The finding supports the hypo-glutamatergic neurotransmission hypothesis in schizophrenia.[11]
## Neurodegenerative disorders
The release of glutamate by system Xc- may lead to excitotoxicity, which is initiated by extrasynaptic NMDA receptors and can cause neuronal death.[12][13] It has been observed that glutamate released from microglia leads to oligodendrocyte death in culture and in the rat optic nerve.[10] However, an increase in system Xc- activity also has a protective effect by increasing levels of glutathione. Oxidative stress has been shown to lead to an increase in system Xc- expression, therefore there must be a balance between the positive protective effects of increased glutathione levels and the negative excitotoxicity effects of increased extrasynaptic glutamate levels.
### Gliomas
A glioma is essentially a glial-derived tumor. These can be induced by an increase in glutamate levels due to an increase in system Xc- activity. Using inhibitors of system Xc- as a treatment for gliomas is currently under active investigation.[10]
### Amyotrophic lateral sclerosis
It has been shown that amyotrophic lateral sclerosis (ALS) is clearly linked to changes in glutamate signaling and glutathione levels; there is also an astrocytic component linked to the disease. All of these factors suggest that a dysfunction in system Xc- may contribute to ALS. It has been observed that an increase in the expression of Nrf2, a transcription factor for system Xc-, leads to a protective effect in mice with ALS symptoms.[10]
### Alzheimer's
There is indirect evidence to suggest that system Xc- might be upregulated in Alzheimer's patients.[10] It has been found in Alzheimer's patients that there is an increase in phosphorylation of the alpha subunit of eukaryotic initiation factor 2 and in expression of transcription factor 4, both of which increase system Xc- expression.[10] It has also been shown that administration of N-acetylcysteine leads to a significant improvement in certain cognitive tasks for Alzheimer's patients.[10]
### Parkinson's disease
Parkinson's disease may be due to mitochondrial dysfunction or oxidative stress, both of which could be caused by a decrease in glutathione levels. Administration of N-acetylcysteine has been shown to counter age-related damage to mitochondria. The therapeutic effects of N-acetylcysteine in the treatment of Parkinson's disease has not been examined yet, though there is a clinical trial that is currently ongoing.[10]
## Neurotoxins
There is evidence that system Xc- may serve as an entry point for neurotoxins and viruses.[10] β-N-methyl-L-alanine (BMAA) is an environmental neurotoxin that can act on system Xc- and inhibit cystine uptake. This leads to a decrease in glutathione levels and an increase in oxidative stress. BMAA can also be transported by system Xc- and lead to an increase in glutamate release and an increase in excitotoxicity. Therefore, BMAA prevents the positive effects of cystine uptake and creates the negative effects of increasing glutamate release.[10] | https://www.wikidoc.org/index.php/SLC7A11 | |
12bfff187e48b19e87be45d76495866977e6bf2a | wikidoc | SLCO1B3 | SLCO1B3
Solute carrier organic anion transporter family member 1B3 (SLCO1B3) also known as organic anion-transporting polypeptide 1B3 (OATP1B3) is a protein that in humans is encoded by the SLCO1B3 gene.
OATP1B3 is a 12-transmembrane domain influx transporter. Normally expressed in the liver, the transporter functions to uptake large, non-polar drugs and hormones from the portal vein.
# Clinical significance
OATP1B3 has also been identified as a transporter aberrantly expressed in prostate cancer and implicated in prostate cancer progression. Increasing mRNA expression of OATP1B3 was also correlated to prostate cancer Gleason score.
In addition, lower expression of OATP1B3 mRNA was also detected in testicular cancer.
# Substrates
Small molecules that are transported by SLCO1B3 include:
- Amanitin
- Atrasentan
- Bilirubin
- Bosentan
- BQ-123
- Bromsulphthalein (BSP)
- CDCA-NBD
- Cholate (CA)
- Cholecystokinin octapeptide (CCK-8)
- Dehydroepiandroserone-3-sulfate (DHEAS)
- Deltorphin II
- Demethylphalloin
- Digoxin
- Docetaxel
- enkephalin (DPDPE)
- Enalapril
- Estradiol-17β-glucuronide 5–25
- Estrone-3-sulfate
- Fexofenadine
- Fluvastatin
- Fluo-3
- Glutathione (GSH)
- Glycocholate (GCA)
- Glycoursodeoxycholate (GUDCA)
- Irinotecan
- Leukotriene C4 (LTC4)
- Methotrexate
- Microcystin
- Monoglyucuronosyl
- Olmesartan
- Ouabain
- Paclitaxel
- Phalloidin
- Pitavastatin
- Rifampicin
- Ro 48-5033 (Bosentan metabolite)
- Rosuvastatin
- SN-38
- Taurocholate (TCA)
- Taurochenodeoxycholate (TCDCA)
- Taurodeoxycholate (TDCA)
- Tauroursodeoxycholate (TUDCA)
- Telmisartan
- Thyroxine (T4)
- TR-14035
- Triiodothyronine (T3)
- Valsartan | SLCO1B3
Solute carrier organic anion transporter family member 1B3 (SLCO1B3) also known as organic anion-transporting polypeptide 1B3 (OATP1B3) is a protein that in humans is encoded by the SLCO1B3 gene.[1]
OATP1B3 is a 12-transmembrane domain influx transporter. Normally expressed in the liver, the transporter functions to uptake large, non-polar drugs and hormones from the portal vein.
# Clinical significance
OATP1B3 has also been identified as a transporter aberrantly expressed in prostate cancer and implicated in prostate cancer progression.[2] Increasing mRNA expression of OATP1B3 was also correlated to prostate cancer Gleason score.[3]
In addition, lower expression of OATP1B3 mRNA was also detected in testicular cancer.[3]
# Substrates
Small molecules that are transported by SLCO1B3 include:[4]
- Amanitin
- Atrasentan
- Bilirubin
- Bosentan
- BQ-123
- Bromsulphthalein (BSP)
- CDCA-NBD
- Cholate (CA)
- Cholecystokinin octapeptide (CCK-8)
- Dehydroepiandroserone-3-sulfate (DHEAS)
- Deltorphin II
- Demethylphalloin
- Digoxin
- Docetaxel
- [D-penicillamine2,5]enkephalin (DPDPE)
- Enalapril
- Estradiol-17β-glucuronide 5–25
- Estrone-3-sulfate
- Fexofenadine
- Fluvastatin
- Fluo-3
- Glutathione (GSH)
- Glycocholate (GCA)
- Glycoursodeoxycholate (GUDCA)
- Irinotecan
- Leukotriene C4 (LTC4)
- Methotrexate
- Microcystin
- Monoglyucuronosyl
- Olmesartan
- Ouabain
- Paclitaxel
- Phalloidin
- Pitavastatin
- Rifampicin
- Ro 48-5033 (Bosentan metabolite)
- Rosuvastatin
- SN-38
- Taurocholate (TCA)
- Taurochenodeoxycholate (TCDCA)
- Taurodeoxycholate (TDCA)
- Tauroursodeoxycholate (TUDCA)
- Telmisartan
- Thyroxine (T4)
- TR-14035
- Triiodothyronine (T3)
- Valsartan | https://www.wikidoc.org/index.php/SLCO1B3 | |
fd2b3edd679f1359329bb18b678bf15f930addaa | wikidoc | SLCO2A1 | SLCO2A1
Solute carrier organic anion transporter family, member 2A1 also known as the prostaglandin transporter (PGT) is a protein that in humans is encoded by the SLCO2A1 gene.
This gene encodes a prostaglandin transporter that is a member of the 12-membrane-spanning organic anion-transporting polypeptide superfamily of transporters. The encoded protein may be involved in mediating the uptake and clearance of prostaglandins in numerous tissues.
# Clinical relevance
Mutations in this gene have been shown to cause primary hypertrophic osteoarthropathy. | SLCO2A1
Solute carrier organic anion transporter family, member 2A1 also known as the prostaglandin transporter (PGT) is a protein that in humans is encoded by the SLCO2A1 gene.[1]
This gene encodes a prostaglandin transporter that is a member of the 12-membrane-spanning organic anion-transporting polypeptide superfamily of transporters. The encoded protein may be involved in mediating the uptake and clearance of prostaglandins in numerous tissues.[1]
# Clinical relevance
Mutations in this gene have been shown to cause primary hypertrophic osteoarthropathy.[2] | https://www.wikidoc.org/index.php/SLCO2A1 | |
8af35f86de4ccaf41d8e3f99d8a8c12e1eb25c2d | wikidoc | SLITRK6 | SLITRK6
SLIT and NTRK-like protein 6 is a protein that in humans is encoded by the SLITRK6 gene.
# Function
Members of the SLITRK family, such as SLITRK6, are integral membrane proteins with 2 N-terminal leucine-rich repeat (LRR) domains similar to those of SLIT proteins (see SLIT1). Most SLITRKs, including SLITRK6, also have C-terminal regions that share homology with neurotrophin receptors (see NTRK1). SLITRKs are expressed predominantly in neural tissues and have neurite-modulating activity.
# Clinical significance
Mutations in SLITRK6 cause high myopia and deafness in humans and mice.
# As a drug target
The protein is the target for the antibody-drug conjugate ASG-15ME which is in phase 1 clinical trials for urothelial cancer. | SLITRK6
SLIT and NTRK-like protein 6 is a protein that in humans is encoded by the SLITRK6 gene.[1][2]
# Function
Members of the SLITRK family, such as SLITRK6, are integral membrane proteins with 2 N-terminal leucine-rich repeat (LRR) domains similar to those of SLIT proteins (see SLIT1). Most SLITRKs, including SLITRK6, also have C-terminal regions that share homology with neurotrophin receptors (see NTRK1). SLITRKs are expressed predominantly in neural tissues and have neurite-modulating activity.[1][2]
# Clinical significance
Mutations in SLITRK6 cause high myopia and deafness in humans and mice.[3]
# As a drug target
The protein is the target for the antibody-drug conjugate ASG-15ME which is in phase 1 clinical trials for urothelial cancer.[4] | https://www.wikidoc.org/index.php/SLITRK6 | |
2529c64fa6b56648245c4c2f5591ea2ea4535aa0 | wikidoc | SMARCA4 | SMARCA4
Transcription activator BRG1 also known as ATP-dependent chromatin remodeler SMARCA4 is a protein that in humans is encoded by the SMARCA4 gene.
# Function
The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44.
BRG1 works to activate or repress transcription. Having functional BRG1 is important for development past the pre-implantation stage. Without having a functional BRG1, exhibited with knockout research, the embryo will not hatch out of the zona pellucida, which will inhibit implantation from occurring on the endometrium (uterine wall). BRG1 is also crucial to the development of sperm. During the first stages of meiosis in spermatogenesis there are high levels of BRG1. When BRG1 is genetically damaged, meiosis is stopped in prophase 1, hindering the development of sperm and would result in infertility. More knockout research has concluded BRG1’s aid in the development of smooth muscle. In a BRG1 knockout, smooth muscle in the gastrointestinal tract lacks contractility, and intestines are incomplete in some cases. Another defect occurring in knocking out BRG1 in smooth muscle development is heart complications such as an open ductus arteriosus after birth.
# Clinical significance
BRG1 (or SMARCA4) is the most frequently mutated chromatin remodeling ATPase in cancer. Mutations in this gene were first recognized in human cancer cell lines derived from adrenal gland and lung. Later it was recognized that mutations exist in a significant frequency of medulloblastoma and pancreatic cancers, and in many other tumor subtypes.
In cancer, mutations in BRG1 show an unusually high preference for missense mutations that are frequently heterozygous and target the ATPase domain. Mutations are enriched at highly conserved ATPase sequences, which lie on important functional surfaces such as the ATP pocket or DNA-binding surface. These mutations act in a genetically dominant manner to alter chromatin regulatory function at enhancers and promoters.
Mutations of BRG1 are associated with context-dependent expression changes at MYC-genes, which indicates that the BRG1 and MYC proteins are functionally related. Another study demonstrated a causal role of BRG1 in the control of retinoic acid and glucocorticoid-induced cell differentiation in lung cancer and in other tumor types. This enables the cancer cell to sustain undifferentiated gene expression programs that affect the control of key cellular processes. Furthermore, it explains why lung cancer and other solid tumors are completely refractory to treatments based on these compounds that are effective therapies for some types of leukemia.
The role of BRG1 in sensitivity or resistance to anti-cancer drugs had been recently highlighted by the elucidation of the mechanisms of action of darinaparsin, an arsenic-based anti-cancer drugs. Darinaparsin has been shown to induce phosphorylation of BRG1, which leads to its exclusion from chromatin. When excluded from the chromatin, BRG1 can no longer act as a transcriptional co-regulator. This leads to the inability of cells to express HO-1, a cytoprotective enzyme.
# Interactions
SMARCA4 has been shown to interact with:
- ACTL6A,
- ARID1A,
- ARID1B,
- BRCA1,
- CTNNB1,
- CBX5,
- CREBBP,
- CCNE1,
- ESR1,
- FANCA,
- HSP90B1,
- ING1,
- Myc,
- NR3C1,
- P53,
- POLR2A,
- PHB,
- SIN3A,
- SMARCB1,
- SMARCC1,
- SMARCC2,
- SMARCE1,
- STAT2, and
- STK11. | SMARCA4
Transcription activator BRG1 also known as ATP-dependent chromatin remodeler SMARCA4 is a protein that in humans is encoded by the SMARCA4 gene.[1]
# Function
The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44.[2]
BRG1 works to activate or repress transcription. Having functional BRG1 is important for development past the pre-implantation stage. Without having a functional BRG1, exhibited with knockout research, the embryo will not hatch out of the zona pellucida, which will inhibit implantation from occurring on the endometrium (uterine wall). BRG1 is also crucial to the development of sperm. During the first stages of meiosis in spermatogenesis there are high levels of BRG1. When BRG1 is genetically damaged, meiosis is stopped in prophase 1, hindering the development of sperm and would result in infertility. More knockout research has concluded BRG1’s aid in the development of smooth muscle. In a BRG1 knockout, smooth muscle in the gastrointestinal tract lacks contractility, and intestines are incomplete in some cases. Another defect occurring in knocking out BRG1 in smooth muscle development is heart complications such as an open ductus arteriosus after birth.[3][4]
# Clinical significance
BRG1 (or SMARCA4) is the most frequently mutated chromatin remodeling ATPase in cancer.[5] Mutations in this gene were first recognized in human cancer cell lines derived from adrenal gland[6] and lung.[7] Later it was recognized that mutations exist in a significant frequency of medulloblastoma and pancreatic cancers, and in many other tumor subtypes.[8][9][10]
In cancer, mutations in BRG1 show an unusually high preference for missense mutations that are frequently heterozygous and target the ATPase domain.[11][5] Mutations are enriched at highly conserved ATPase sequences[12], which lie on important functional surfaces such as the ATP pocket or DNA-binding surface.[11] These mutations act in a genetically dominant manner to alter chromatin regulatory function at enhancers[11] and promoters.[12]
Mutations of BRG1 are associated with context-dependent expression changes at MYC-genes, which indicates that the BRG1 and MYC proteins are functionally related.[11][7][13] Another study demonstrated a causal role of BRG1 in the control of retinoic acid and glucocorticoid-induced cell differentiation in lung cancer and in other tumor types. This enables the cancer cell to sustain undifferentiated gene expression programs that affect the control of key cellular processes. Furthermore, it explains why lung cancer and other solid tumors are completely refractory to treatments based on these compounds that are effective therapies for some types of leukemia.[14]
The role of BRG1 in sensitivity or resistance to anti-cancer drugs had been recently highlighted by the elucidation of the mechanisms of action of darinaparsin, an arsenic-based anti-cancer drugs. Darinaparsin has been shown to induce phosphorylation of BRG1, which leads to its exclusion from chromatin. When excluded from the chromatin, BRG1 can no longer act as a transcriptional co-regulator. This leads to the inability of cells to express HO-1, a cytoprotective enzyme.[15]
# Interactions
SMARCA4 has been shown to interact with:
- ACTL6A,[16][17]
- ARID1A,[16][17]
- ARID1B,[18][19]
- BRCA1,[20][21]
- CTNNB1,[22]
- CBX5,[23]
- CREBBP,[24][25]
- CCNE1,[26][27]
- ESR1,[24][28]
- FANCA,[29][30]
- HSP90B1,[29]
- ING1,[31]
- Myc,[32][33]
- NR3C1,[34][35]
- P53,[36]
- POLR2A,[16][17][37]
- PHB,[38]
- SIN3A,[31][37]
- SMARCB1,[16][17][29][37][39]
- SMARCC1,[16][17][29][37]
- SMARCC2,[16][17][29]
- SMARCE1,[16][17]
- STAT2,[40] and
- STK11.[41] | https://www.wikidoc.org/index.php/SMARCA4 | |
803b7739e22abdaea21e0a1a937eacf66a9c0a0d | wikidoc | SMARCA5 | SMARCA5
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 is a protein that in humans is encoded by the SMARCA5 gene.
# Function
The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The protein encoded by this gene is a component of the chromatin remodeling and spacing factor RSF, a facilitator of the transcription of class II genes by RNA polymerase II. The encoded protein is similar in sequence to the Drosophila ISWI chromatin remodeling protein.
# Interactions
SMARCA5 has been shown to interact with RAD21, Histone deacetylase 2, POLE3, SATB1 and BAZ1A. | SMARCA5
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 is a protein that in humans is encoded by the SMARCA5 gene.[1][2]
# Function
The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The protein encoded by this gene is a component of the chromatin remodeling and spacing factor RSF, a facilitator of the transcription of class II genes by RNA polymerase II. The encoded protein is similar in sequence to the Drosophila ISWI chromatin remodeling protein.[2]
# Interactions
SMARCA5 has been shown to interact with RAD21,[3] Histone deacetylase 2,[3] POLE3,[4] SATB1[5] and BAZ1A.[3][4][5][6][7] | https://www.wikidoc.org/index.php/SMARCA5 | |
7435b0cefec72b26b7531d1f3adaf8c84777618a | wikidoc | SMARCE1 | SMARCE1
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 is a protein that in humans is encoded by the SMARCE1 gene.
# Function
The protein encoded by this gene is part of the large ATP-dependent chromatin remodeling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. The encoded protein, either alone or when in the SWI/SNF complex, can bind to 4-way junction DNA, which is thought to mimic the topology of DNA as it enters or exits the nucleosome. The protein contains a DNA-binding HMG domain, but disruption of this domain does not abolish the DNA-binding or nucleosome-displacement activities of the SWI/SNF complex. Unlike most of the SWI/SNF complex proteins, this protein has no yeast counterpart.
# Interactions
SMARCE1 has been shown to interact with Estrogen receptor alpha, SMARCB1 and SMARCA4. | SMARCE1
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 is a protein that in humans is encoded by the SMARCE1 gene.[1][2]
# Function
The protein encoded by this gene is part of the large ATP-dependent chromatin remodeling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. The encoded protein, either alone or when in the SWI/SNF complex, can bind to 4-way junction DNA, which is thought to mimic the topology of DNA as it enters or exits the nucleosome. The protein contains a DNA-binding HMG domain, but disruption of this domain does not abolish the DNA-binding or nucleosome-displacement activities of the SWI/SNF complex. Unlike most of the SWI/SNF complex proteins, this protein has no yeast counterpart.[2]
# Interactions
SMARCE1 has been shown to interact with Estrogen receptor alpha,[3] SMARCB1[4][5] and SMARCA4.[4][5] | https://www.wikidoc.org/index.php/SMARCE1 | |
28286690e86d7237e12437f34ff90789eacbe5f5 | wikidoc | SSASDSA | SSASDSA
# 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
SSASDSA is {{{aOrAn}}} {{{drugClass}}} that is FDA approved for the {{{indicationType}}} of {{{indication}}}. Common adverse reactions include {{{adverseReactions}}}.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
There is limited information regarding SSASDSA FDA-Labeled Indications and Dosage (Adult) in the drug label.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of SSASDSA in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of SSASDSA in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding SSASDSA FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of SSASDSA in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of SSASDSA in pediatric patients.
# Contraindications
There is limited information regarding SSASDSA Contraindications in the drug label.
# Warnings
There is limited information regarding SSASDSA Warnings' in the drug label.
# Adverse Reactions
## Clinical Trials Experience
There is limited information regarding SSASDSA Clinical Trials Experience in the drug label.
## Postmarketing Experience
There is limited information regarding SSASDSA Postmarketing Experience in the drug label.
# Drug Interactions
There is limited information regarding SSASDSA Drug Interactions in the drug label.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of SSASDSA in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of SSASDSA in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of SSASDSA during labor and delivery.
### Nursing Mothers
There is no FDA guidance on the use of SSASDSA in women who are nursing.
### Pediatric Use
There is no FDA guidance on the use of SSASDSA in pediatric settings.
### Geriatic Use
There is no FDA guidance on the use of SSASDSA in geriatric settings.
### Gender
There is no FDA guidance on the use of SSASDSA with respect to specific gender populations.
### Race
There is no FDA guidance on the use of SSASDSA with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of SSASDSA in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of SSASDSA in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of SSASDSA in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of SSASDSA in patients who are immunocompromised.
# Administration and Monitoring
### Administration
There is limited information regarding SSASDSA Administration in the drug label.
### Monitoring
There is limited information regarding SSASDSA Monitoring in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of SSASDSA and IV administrations.
# Overdosage
There is limited information regarding SSASDSA overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
# Pharmacology
There is limited information regarding SSASDSA Pharmacology in the drug label.
## Mechanism of Action
There is limited information regarding SSASDSA Mechanism of Action in the drug label.
## Structure
There is limited information regarding SSASDSA Structure in the drug label.
## Pharmacodynamics
There is limited information regarding SSASDSA Pharmacodynamics in the drug label.
## Pharmacokinetics
There is limited information regarding SSASDSA Pharmacokinetics in the drug label.
## Nonclinical Toxicology
There is limited information regarding SSASDSA Nonclinical Toxicology in the drug label.
# Clinical Studies
There is limited information regarding SSASDSA Clinical Studies in the drug label.
# How Supplied
There is limited information regarding SSASDSA How Supplied in the drug label.
## Storage
There is limited information regarding SSASDSA Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding SSASDSA Patient Counseling Information in the drug label.
# Precautions with Alcohol
Alcohol-SSASDSA 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 SSASDSA Brand Names in the drug label.
# Look-Alike Drug Names
There is limited information regarding SSASDSA Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | SSASDSA
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];
# 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
SSASDSA is {{{aOrAn}}} {{{drugClass}}} that is FDA approved for the {{{indicationType}}} of {{{indication}}}. Common adverse reactions include {{{adverseReactions}}}.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
There is limited information regarding SSASDSA FDA-Labeled Indications and Dosage (Adult) in the drug label.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of SSASDSA in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of SSASDSA in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding SSASDSA FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of SSASDSA in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of SSASDSA in pediatric patients.
# Contraindications
There is limited information regarding SSASDSA Contraindications in the drug label.
# Warnings
There is limited information regarding SSASDSA Warnings' in the drug label.
# Adverse Reactions
## Clinical Trials Experience
There is limited information regarding SSASDSA Clinical Trials Experience in the drug label.
## Postmarketing Experience
There is limited information regarding SSASDSA Postmarketing Experience in the drug label.
# Drug Interactions
There is limited information regarding SSASDSA Drug Interactions in the drug label.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of SSASDSA in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of SSASDSA in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of SSASDSA during labor and delivery.
### Nursing Mothers
There is no FDA guidance on the use of SSASDSA in women who are nursing.
### Pediatric Use
There is no FDA guidance on the use of SSASDSA in pediatric settings.
### Geriatic Use
There is no FDA guidance on the use of SSASDSA in geriatric settings.
### Gender
There is no FDA guidance on the use of SSASDSA with respect to specific gender populations.
### Race
There is no FDA guidance on the use of SSASDSA with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of SSASDSA in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of SSASDSA in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of SSASDSA in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of SSASDSA in patients who are immunocompromised.
# Administration and Monitoring
### Administration
There is limited information regarding SSASDSA Administration in the drug label.
### Monitoring
There is limited information regarding SSASDSA Monitoring in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of SSASDSA and IV administrations.
# Overdosage
There is limited information regarding SSASDSA overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
# Pharmacology
There is limited information regarding SSASDSA Pharmacology in the drug label.
## Mechanism of Action
There is limited information regarding SSASDSA Mechanism of Action in the drug label.
## Structure
There is limited information regarding SSASDSA Structure in the drug label.
## Pharmacodynamics
There is limited information regarding SSASDSA Pharmacodynamics in the drug label.
## Pharmacokinetics
There is limited information regarding SSASDSA Pharmacokinetics in the drug label.
## Nonclinical Toxicology
There is limited information regarding SSASDSA Nonclinical Toxicology in the drug label.
# Clinical Studies
There is limited information regarding SSASDSA Clinical Studies in the drug label.
# How Supplied
There is limited information regarding SSASDSA How Supplied in the drug label.
## Storage
There is limited information regarding SSASDSA Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding SSASDSA Patient Counseling Information in the drug label.
# Precautions with Alcohol
Alcohol-SSASDSA 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 SSASDSA Brand Names in the drug label.
# Look-Alike Drug Names
There is limited information regarding SSASDSA Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/SSASDSA | |
609fb6da0e0e712b58c845406abce569327ff4cd | wikidoc | ST3GAL3 | ST3GAL3
ST3 beta-galactoside alpha-2,3-sialyltransferase 3, also known as ST3GAL3, is a protein which in humans is encoded by the ST3GAL3 gene.
# Function
The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein is normally found in the Golgi apparatus but can be proteolytically processed to a soluble form. This protein is a member of glycosyltransferase family 29. Multiple transcript variants encoding several different isoforms have been found for this gene.
Mutations in the ST3GAL3 gene was recently shown to be the cause of autosomal recessive mental retardation 12. Since the mutations disrupt a glycosylation pathway, this disorder may be considererd a congenital disorder of glycosylation. | ST3GAL3
ST3 beta-galactoside alpha-2,3-sialyltransferase 3, also known as ST3GAL3, is a protein which in humans is encoded by the ST3GAL3 gene.[1][2]
# Function
The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein is normally found in the Golgi apparatus but can be proteolytically processed to a soluble form. This protein is a member of glycosyltransferase family 29. Multiple transcript variants encoding several different isoforms have been found for this gene.[2]
Mutations in the ST3GAL3 gene was recently shown to be the cause of autosomal recessive mental retardation 12. Since the mutations disrupt a glycosylation pathway, this disorder may be considererd a congenital disorder of glycosylation. | https://www.wikidoc.org/index.php/ST3GAL3 | |
65f2758cf528c183197a4ddbf63fb5bed3d7637b | wikidoc | ST3GAL5 | ST3GAL5
Lactosylceramide alpha-2,3-sialyltransferase is an enzyme that in humans is encoded by the ST3GAL5 gene.
Ganglioside GM3 is known to participate in the induction of cell differentiation, modulation of cell proliferation, maintenance of fibroblast morphology, signal transduction, and integrin-mediated cell adhesion. The protein encoded by this gene is a type II membrane protein which catalyzes the formation of GM3 using lactosylceramide as the substrate. The encoded protein is a member of glycosyltransferase family 29 and may be localized to the Golgi apparatus. Mutation in this gene has been associated with Amish infantile epilepsy syndrome. Transcript variants encoding different isoforms have been found for this gene.
Mutations in this gene have also been associated to ‘Salt & Pepper’ syndrome: an autosomal recessive condition characterized by severe intellectual disability, epilepsy, scoliosis, choreoathetosis, dysmorphic facial features and altered dermal pigmentation. (doi: 10.1093/hmg/ddt434) | ST3GAL5
Lactosylceramide alpha-2,3-sialyltransferase is an enzyme that in humans is encoded by the ST3GAL5 gene.[1][2]
Ganglioside GM3 is known to participate in the induction of cell differentiation, modulation of cell proliferation, maintenance of fibroblast morphology, signal transduction, and integrin-mediated cell adhesion. The protein encoded by this gene is a type II membrane protein which catalyzes the formation of GM3 using lactosylceramide as the substrate. The encoded protein is a member of glycosyltransferase family 29 and may be localized to the Golgi apparatus. Mutation in this gene has been associated with Amish infantile epilepsy syndrome. Transcript variants encoding different isoforms have been found for this gene.[2]
Mutations in this gene have also been associated to ‘Salt & Pepper’ syndrome: an autosomal recessive condition characterized by severe intellectual disability, epilepsy, scoliosis, choreoathetosis, dysmorphic facial features and altered dermal pigmentation. (doi: 10.1093/hmg/ddt434) | https://www.wikidoc.org/index.php/ST3GAL5 | |
3883dfa09ed09d91f619fff19119bf1433f5d698 | wikidoc | ST6GAL1 | ST6GAL1
Beta-galactoside alpha-2,6-sialyltransferase 1 is an enzyme that in humans is encoded by the ST6GAL1 gene.
The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein, which is normally found in the Golgi but which can be proteolytically processed to a soluble form, is involved in the generation of the cell-surface carbohydrate determinants and differentiation antigens HB-6, CDw75, and CD76. This protein is a member of glycosyltransferase family 29. Three transcript variants encoding two different isoforms have been found for this gene.
Transcripts of ST6GAL1 are found in mouse high endothelial cells of mesenteric lymph node and Peyer's patches, and it could be involved in the B cell homing to Peyer's patches. | ST6GAL1
Beta-galactoside alpha-2,6-sialyltransferase 1 is an enzyme that in humans is encoded by the ST6GAL1 gene.[1]
The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein, which is normally found in the Golgi but which can be proteolytically processed to a soluble form, is involved in the generation of the cell-surface carbohydrate determinants and differentiation antigens HB-6, CDw75, and CD76. This protein is a member of glycosyltransferase family 29. Three transcript variants encoding two different isoforms have been found for this gene.[2]
Transcripts of ST6GAL1 are found in mouse high endothelial cells of mesenteric lymph node and Peyer's patches, and it could be involved in the B cell homing to Peyer's patches.[3] | https://www.wikidoc.org/index.php/ST6GAL1 | |
07b946e1720d60b3aabf3a99b9dee6a68215d1b5 | wikidoc | ST8SIA1 | ST8SIA1
Alpha-N-acetylneuraminide alpha-2,8-sialyltransferase is an enzyme that in humans is encoded by the ST8SIA1 gene.
Gangliosides are membrane-bound glycosphingolipids containing sialic acid. Ganglioside GD3 is known to be important for cell adhesion and growth of cultured malignant cells. The protein encoded by ST8SIA1 is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to GM3 to produce gangliosides GD3 and GT3. The encoded protein may be found in the Golgi apparatus and is a member of glycosyltransferase family 29.
In melanocytic cells, ST8SIA1 gene expression may be regulated by MITF. | ST8SIA1
Alpha-N-acetylneuraminide alpha-2,8-sialyltransferase is an enzyme that in humans is encoded by the ST8SIA1 gene.[1][2]
Gangliosides are membrane-bound glycosphingolipids containing sialic acid. Ganglioside GD3 is known to be important for cell adhesion and growth of cultured malignant cells. The protein encoded by ST8SIA1 is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to GM3 to produce gangliosides GD3 and GT3. The encoded protein may be found in the Golgi apparatus and is a member of glycosyltransferase family 29.[2]
In melanocytic cells, ST8SIA1 gene expression may be regulated by MITF.[3] | https://www.wikidoc.org/index.php/ST8SIA1 | |
a1d07f6dfaa4fa3757ddd963a4fb17138a6b6dc1 | wikidoc | STARD13 | STARD13
StAR-related lipid transfer domain protein 13 (STARD13) also known as deleted in liver cancer 2 protein (DLC-2) is a protein that in humans is encoded by the STARD13 gene and a member of the DLC family of proteins.
# Function and structure
STARD13 serves as a Rho GTPase-activating protein (GAP), a type of protein that regulates members of the Rho family of GTPases. It selectively activates RhoA and CDC42 and suppresses cell growth by inhibiting actin stress fiber assembly.
The protein consists of an N-terminal sterile alpha motif (SAM) domain, a serine-rich domain, a RhoGAP domain and at the C-terminus, a StAR-related lipid-transfer domain (START).
# Tissue distribution and pathology
The protein was identified in part through its differential expression in cancers. A low level of STARD13 was observed in less differentiated hepatocellular carcinoma tissue with higher RhoA expression. A small patient study finds that the absence of STARD13 in hepatocellular carcinomas correlates with higher levels of RhoA and a poorer prognosis than patients with carcinomas that were STARD13-positive.
# Model organisms
Model organisms have been used in the study of STARD13 function. A conditional knockout mouse line, called Stard13tm1a(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 — at the Wellcome Trust Sanger Institute.
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 two significant abnormalities were observed. Female homozygous mutants had an increased susceptibility to Citrobacter infection and displayed a decreased hematocrit and hemoglobin content.
Another study of mice lacking STARD13, found it may promote blood vessel formation (angiogenesis), especially by tumor cells. The promotion of angiogenesis with the loss of STARD13 occurs through the actions of RhoA. | STARD13
StAR-related lipid transfer domain protein 13 (STARD13) also known as deleted in liver cancer 2 protein (DLC-2) is a protein that in humans is encoded by the STARD13 gene and a member of the DLC family of proteins.[1][2]
# Function and structure
STARD13 serves as a Rho GTPase-activating protein (GAP), a type of protein that regulates members of the Rho family of GTPases.[3] It selectively activates RhoA and CDC42 and suppresses cell growth by inhibiting actin stress fiber assembly.[3]
The protein consists of an N-terminal sterile alpha motif (SAM) domain,[4] a serine-rich domain, a RhoGAP domain and at the C-terminus, a StAR-related lipid-transfer domain (START).
# Tissue distribution and pathology
The protein was identified in part through its differential expression in cancers. A low level of STARD13 was observed in less differentiated hepatocellular carcinoma tissue with higher RhoA expression. A small patient study finds that the absence of STARD13 in hepatocellular carcinomas correlates with higher levels of RhoA and a poorer prognosis than patients with carcinomas that were STARD13-positive.[5]
# Model organisms
Model organisms have been used in the study of STARD13 function. A conditional knockout mouse line, called Stard13tm1a(KOMP)Wtsi[11][12] 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 — at the Wellcome Trust Sanger Institute.[13][14][15]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty four tests were carried out on mutant mice and two significant abnormalities were observed. Female homozygous mutants had an increased susceptibility to Citrobacter infection and displayed a decreased hematocrit and hemoglobin content.[9]
Another study of mice lacking STARD13, found it may promote blood vessel formation (angiogenesis), especially by tumor cells.[17] The promotion of angiogenesis with the loss of STARD13 occurs through the actions of RhoA.[17] | https://www.wikidoc.org/index.php/STARD13 | |
5ed4f5c4120d335bc4c1891ea426785e9e51e094 | wikidoc | STK35L1 | STK35L1
STK35L1 is a protein that in humans is encoded by the STK35 (serine/threonine kinase 35) gene.
It is a member of the NKF4 (New Kinase Family 4) Ser/Thr kinases (STK) family and classified in group "Other" in the human kinome.
Previously, STK35L1 was named as Clik1 (CLP36 Interacting Kinase 1) based on a study that showed an association of STK35 with CLP36 after overexpression of both proteins in osteosarcoma cells. Clik1 gene described by Vallenius et al. code for a protein of 501 amino acids. Later, Goyal et al. found that coding sequence of the STK35 gene is incomplete. The newly identified sequence of the STK35 gene codes for a protein of 534 amino acids with a N-terminal elongation of 133 amino acids. It has been designated as STK35L1.
# Functions
STK35L1 is predominantly found in the nucleus and the nucleolus. Nuclear actin was identified as a novel binding partner of STK35L1. However, it can interact with PDLIM1/CLP-36 in the cytoplasm and localize to actin stress fibers. STK35L1 regulates the expression of CDKN2A and inhibiting G1- to S-phase transition.Depletion of STK35L1 by siRNA impaired endothelial cell migration. STK35L1 may act as a central kinase linking the cell cycle and migration of endothelial cells. | STK35L1
STK35L1 is a protein that in humans is encoded by the STK35 (serine/threonine kinase 35) gene.[1]
It is a member of the NKF4 (New Kinase Family 4) Ser/Thr kinases (STK) family and classified in group "Other" in the human kinome.
Previously, STK35L1 was named as Clik1 (CLP36 Interacting Kinase 1) based on a study that showed an association of STK35 with CLP36 after overexpression of both proteins in osteosarcoma cells.[2][3] Clik1 gene described by Vallenius et al. code for a protein of 501 amino acids. Later, Goyal et al. found that coding sequence of the STK35 gene is incomplete. The newly identified sequence of the STK35 gene codes for a protein of 534 amino acids with a N-terminal elongation of 133 amino acids. It has been designated as STK35L1.
# Functions
STK35L1 is predominantly found in the nucleus and the nucleolus. Nuclear actin was identified as a novel binding partner of STK35L1.[4] However, it can interact with PDLIM1/CLP-36 in the cytoplasm and localize to actin stress fibers. STK35L1 regulates the expression of CDKN2A and inhibiting G1- to S-phase transition.Depletion of STK35L1 by siRNA impaired endothelial cell migration. STK35L1 may act as a central kinase linking the cell cycle and migration of endothelial cells. | https://www.wikidoc.org/index.php/STK35L1 | |
f885a334ccb340da8293845d2398bd419f9e89cf | wikidoc | SULT1C3 | SULT1C3
Sulfotransferase 1C3, also known as ST1C3, is an enzyme that in humans is encoded by the SULT1C3 gene.
# Function
Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members.
# Clinical significance
ST1C3 sulfates large benzylic alcohols such as 1-hydroxymethyl-pyrene to chemically reactive mutagenic sulpho conjugates. | SULT1C3
Sulfotransferase 1C3, also known as ST1C3, is an enzyme that in humans is encoded by the SULT1C3 gene.[1][2][3]
# Function
Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members.[1]
# Clinical significance
ST1C3 sulfates large benzylic alcohols such as 1-hydroxymethyl-pyrene to chemically reactive mutagenic sulpho conjugates.[4] | https://www.wikidoc.org/index.php/SULT1C3 | |
8a0d7743e011616e46838d08bde4291a6669001f | wikidoc | SUPV3L1 | SUPV3L1
ATP-dependent RNA helicase SUPV3L1, mitochondrial is an enzyme that in humans is encoded by the SUPV3L1 gene.
# Model organisms
Model organisms have been used in the study of SUPV3L1 function. A conditional knockout mouse line, called Supv3l1tm1a(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 — at the Wellcome Trust Sanger Institute.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.
Twenty six tests were carried out and three significant phenotypes were reported. All homozygous mutant animals died prior to birth, and therefore none were observed at weaning. The remaining tests were carried out on heterozygous mutant mice and radiography showed female animals had defects in their transverse processes. | SUPV3L1
ATP-dependent RNA helicase SUPV3L1, mitochondrial is an enzyme that in humans is encoded by the SUPV3L1 gene.[1][2][3]
# Model organisms
Model organisms have been used in the study of SUPV3L1 function. A conditional knockout mouse line, called Supv3l1tm1a(EUCOMM)Wtsi[9][10] 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 — at the Wellcome Trust Sanger Institute.[11][12][13]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[7][14]
Twenty six tests were carried out and three significant phenotypes were reported. All homozygous mutant animals died prior to birth, and therefore none were observed at weaning. The remaining tests were carried out on heterozygous mutant mice and radiography showed female animals had defects in their transverse processes.[7] | https://www.wikidoc.org/index.php/SUPV3L1 | |
369f71c9f85e3fcfd2ac7ec4a7529224847ac68e | wikidoc | SYNGAP1 | SYNGAP1
Synaptic Ras GTPase-activating protein 1, also known as synaptic Ras-GAP 1 or SYNGAP1, is a protein that in humans is encoded by the SYNGAP1 gene. SYNGAP1 is a ras GTPase-activating protein that is critical for the development of cognition and proper synapse function. Mutations in humans can cause intellectual disability or epilepsy.
# Function
SynGAP1 is a complex protein with several functions that may be regulated temporally via complex isoforms. A well-documented function of SynGAP1 involves NMDA receptor-mediated synaptic plasticity and membrane insertion of AMPA receptors through the suppression of upstream signaling pathways. However, SynGAP1 has also been shown to function cooperatively with Unc51.1 in axon formation. One way SynGAP1 affects these processes is through the MAP kinase signaling pathway by attenuation of Ras signalling. However, alternative splicing and multiple translational start sites have been shown to cause opposing effects, illustrating the importance of multiple functional domains that reside within the c- and n-termini. For example, the expression of an α1 or α2 c-terminal variant of SynGAP1 will either increase or decrease synaptic strength, respectively. Overall, SynGAP1 is essential for development and survival, which is evident as knockout mice die perinatally.
## Dendritic spine development and maturation
SynGAP1 is shown to localize at the postsynaptic density on the dendritic spines of excitatory synapses. Cultured neurons of SynGAP heterozygotic and homozygotic knockout mice display accelerated maturation of dendritic spines, including an increase in overall spine size, which produces more mushroom shaped and less stubby spines. Spine heads are enlarged due to the increased phosphorylation of cofilin, leading to a decrease in F-actin severing and turnover. The increased size of the dendritic spines also corresponded to an increase in membrane bound AMPARs or a decrease in silent synapses. These neurons displayed a higher frequency and larger amplitudes of miniature excitatory postsynaptic potentials (mEPSP). Mice models with domain specific mutations led to neonatal hyperactivity of the hippocampal trisynaptic circuit. Mutations had the greatest impact during the first 3 weeks of development, and reversal of mutations in adults did not improve behavior and cognition.
# Clinical significance
Several mutations in the SYNGAP1 gene were identified as the cause of intellectual disability. Intellectual disability is sometimes associated with syndromes of other defects caused by the same gene, but SYNGAP1-associated intellectual disability is not; it is therefore called non-syndromic intellectual disability. Since neither of the parents of children with this condition have the mutation, this means it was a sporadic mutation that occurred during division of the parents' gametes (meiosis) or fertilization of the egg. It is a dominant mutation, which means that the individual will be developmentally disabled even if only one allele is mutated.
Mutations in this gene have also been found associated to cases of epileptic encephalopathies.
# Interactions
SYNGAP1 has been shown to interact with DLG3 and ULK1. | SYNGAP1
Synaptic Ras GTPase-activating protein 1, also known as synaptic Ras-GAP 1 or SYNGAP1, is a protein that in humans is encoded by the SYNGAP1 gene.[1][2][3] SYNGAP1 is a ras GTPase-activating protein that is critical for the development of cognition and proper synapse function. Mutations in humans can cause intellectual disability or epilepsy.
# Function
SynGAP1 is a complex protein with several functions that may be regulated temporally via complex isoforms.[4] A well-documented function of SynGAP1 involves NMDA receptor-mediated synaptic plasticity and membrane insertion of AMPA receptors through the suppression of upstream signaling pathways.[5] However, SynGAP1 has also been shown to function cooperatively with Unc51.1 in axon formation.[6] One way SynGAP1 affects these processes is through the MAP kinase signaling pathway by attenuation of Ras signalling.[7] However, alternative splicing and multiple translational start sites have been shown to cause opposing effects, illustrating the importance of multiple functional domains that reside within the c- and n-termini. For example, the expression of an α1 or α2 c-terminal variant of SynGAP1 will either increase or decrease synaptic strength, respectively.[4] Overall, SynGAP1 is essential for development and survival, which is evident as knockout mice die perinatally.[8]
## Dendritic spine development and maturation
SynGAP1 is shown to localize at the postsynaptic density on the dendritic spines of excitatory synapses.[2] Cultured neurons of SynGAP heterozygotic and homozygotic knockout mice display accelerated maturation of dendritic spines, including an increase in overall spine size, which produces more mushroom shaped and less stubby spines.[5][7][9] Spine heads are enlarged due to the increased phosphorylation of cofilin, leading to a decrease in F-actin severing and turnover.[10] The increased size of the dendritic spines also corresponded to an increase in membrane bound AMPARs or a decrease in silent synapses. These neurons displayed a higher frequency and larger amplitudes of miniature excitatory postsynaptic potentials (mEPSP).[9] Mice models with domain specific mutations led to neonatal hyperactivity of the hippocampal trisynaptic circuit. Mutations had the greatest impact during the first 3 weeks of development, and reversal of mutations in adults did not improve behavior and cognition.[5]
# Clinical significance
Several mutations in the SYNGAP1 gene were identified as the cause of intellectual disability. Intellectual disability is sometimes associated with syndromes of other defects caused by the same gene, but SYNGAP1-associated intellectual disability is not; it is therefore called non-syndromic intellectual disability. Since neither of the parents of children with this condition have the mutation, this means it was a sporadic mutation that occurred during division of the parents' gametes (meiosis) or fertilization of the egg. It is a dominant mutation, which means that the individual will be developmentally disabled even if only one allele is mutated.[11]
Mutations in this gene have also been found associated to cases of epileptic encephalopathies.[12]
# Interactions
SYNGAP1 has been shown to interact with DLG3[2] and ULK1.[6] | https://www.wikidoc.org/index.php/SYNGAP1 | |
b2feb42dd3c6532de788ef58c0c87bf73fa68aa5 | wikidoc | Saccade | Saccade
A saccade is a fast movement of an eye, head or other part of an animal's body or device. It can also be a fast shift in frequency of an emitted signal or other quick change. However, this article deals with saccadic eye motion.
With respect to the eye, saccades are quick, simultaneous movements of both eyes in the same direction. Initiated by the frontal lobe of the brain (Brodmann area 8), saccades serve as a mechanism for fixation, rapid eye movement and the fast phase of optokinetic nystagmus. The word appears to have been coined in the 1880s by French ophthalmologist Émile Javal, who used a mirror on one side of a page to observe eye movement in silent reading, and found that it involves a succession of discontinuous individual movements.
# Function
Humans and other animals do not look at a scene in a steady way. Instead, the eyes move around, locating interesting parts of the scene and building up a mental 'map' corresponding to the scene. One reason for saccades of the human eye is that the central part of the retina, the fovea, plays a critical role in resolving objects. By moving the eye so that small parts of a scene can be sensed with greater resolution, body resources can be used more efficiently.
# Velocity and duration
The dynamics of saccadic eye motion give insight into the complexity of the mechanism that controls the motion of the eye. The saccade is the fastest movement of an external part of the human body. The peak angular speed of the eye during a saccade reaches up to 1000 degrees per second. Saccades last from about 20 to 200 milliseconds.
The duration of a saccade depends on its amplitude. The amplitude of a saccade is the angular distance that the eye needs to travel during the movement. For amplitudes up to about 60 degrees, the duration of a saccade linearly depends on the amplitude (so called "saccadic main sequence"). In that range, the peak velocity of a saccade linearly depends on the amplitude. In saccades larger than 60 degrees, the peak velocity remains constant at the maximum velocity attainable by the eye. Thus, the duration of these large saccades is no longer linearly dependent on the amplitude.
In addition to the kind of saccades described above, the human eye is in a constant state of vibration, oscillating back and forth at a rate of about 60 per second. These microsaccades are tiny movements, roughly 20 arcseconds in excursion and are completely imperceptible under normal circumstances. They serve to refresh the image being cast onto the rod cells and cone cells at the back of the eye. Without microsaccades, staring fixedly at something would cause the vision to cease after a few seconds since rods and cones only respond to a change in luminance.
# Pathophysiologic saccades
Saccadic oscillations not filling the normal function are a deviation from a healthy or normal condition.
## Causes
- Nystagmus is characterised by the combination of a smooth pursuit, which usually acts to take the eye off the point of regard, interspersed with the saccadic movement that serves to bring the eye back on target.
- Opsoclonus or ocular flutter, on the other hand, are composed purely of fast-phase saccadic eye movements.
Without the use of objective recording techniques, it may be very difficult to distinguish between these conditions.
# Saccadic masking
It is a common but false belief that during the saccade, no information is passed through the optic nerve to the brain. Whereas low spatial frequencies (the 'fuzzier' parts) are attenuated, higher spatial frequencies (an image's fine details) which would otherwise be blurred out by the eye movement remain unaffected. This phenomenon, known as saccadic masking or saccadic suppression, is known to occur in the time preceding a saccadic eye movement, implying neurological reasons for the effect, rather than simply the image's motion blur.
A person may observe the saccadic masking effect by standing in front of a mirror and looking from one eye to the next (and vice versa). The subject will not experience any movement of the eyes nor any evidence that the optic nerve has momentarily ceased transmitting. Due to saccadic masking, the eye/brain system not only hides the eye movements from the individual but also hides the evidence that anything has been hidden. Of course, a second observer watching the experiment will see the subject's eyes moving back and forth.
# Comparative physiology
Saccades are a widespread phenomenon across animals with image-forming visual systems. They have been observed in animals across three phyla, including animals that do not have a fovea (most vertebrates do not) and animals that cannot move their eyes independently of their head (such as insects). Therefore, while saccades serve in humans and other primates to increase the effective visual resolution of a scene, there must be additional reasons for the behavior. The most frequently suggested of these reasons is to avoid blurring of the image, which would occur if the response time of a photoreceptor is longer than the time a given portion of the image is stimulating that photoreceptor as the image drifts across the eye.
In birds, saccadic eye movements serve a further function. The avian retina is highly developed. It is thicker than the mammalian retina and has a higher metabolic activity, but it lacks proper vasculature. Therefore, the retinal cells must obtain nutrients via diffusion through the choroid and from the vitreous humor. The pecten is a specialised structure in the avian retina. It is a highly vascular structure that projects into the vitreous humor. Experimentally, it has been shown that during saccadic eye oscillations (which occupy up to 12% of avian viewing time), the pecten acts as an agitator, propelling perfusate towards the retina. Thus, in birds, saccadic eye movements appear to be important in retinal nutrition and respiration. | Saccade
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
A saccade is a fast movement of an eye, head or other part of an animal's body or device. It can also be a fast shift in frequency of an emitted signal or other quick change. However, this article deals with saccadic eye motion.
With respect to the eye, saccades are quick, simultaneous movements of both eyes in the same direction.[1] Initiated by the frontal lobe of the brain (Brodmann area 8), saccades serve as a mechanism for fixation, rapid eye movement and the fast phase of optokinetic nystagmus.[1] The word appears to have been coined in the 1880s by French ophthalmologist Émile Javal, who used a mirror on one side of a page to observe eye movement in silent reading, and found that it involves a succession of discontinuous individual movements.[2]
# Function
Humans and other animals do not look at a scene in a steady way. Instead, the eyes move around, locating interesting parts of the scene and building up a mental 'map' corresponding to the scene. One reason for saccades of the human eye is that the central part of the retina, the fovea, plays a critical role in resolving objects. By moving the eye so that small parts of a scene can be sensed with greater resolution, body resources can be used more efficiently.
# Velocity and duration
The dynamics of saccadic eye motion give insight into the complexity of the mechanism that controls the motion of the eye. The saccade is the fastest movement of an external part of the human body. The peak angular speed of the eye during a saccade reaches up to 1000 degrees per second. Saccades last from about 20 to 200 milliseconds.
The duration of a saccade depends on its amplitude. The amplitude of a saccade is the angular distance that the eye needs to travel during the movement. For amplitudes up to about 60 degrees, the duration of a saccade linearly depends on the amplitude (so called "saccadic main sequence"). In that range, the peak velocity of a saccade linearly depends on the amplitude. In saccades larger than 60 degrees, the peak velocity remains constant at the maximum velocity attainable by the eye. Thus, the duration of these large saccades is no longer linearly dependent on the amplitude.
In addition to the kind of saccades described above, the human eye is in a constant state of vibration, oscillating back and forth at a rate of about 60 per second. These microsaccades are tiny movements, roughly 20 arcseconds in excursion and are completely imperceptible under normal circumstances. They serve to refresh the image being cast onto the rod cells and cone cells at the back of the eye. Without microsaccades, staring fixedly at something would cause the vision to cease after a few seconds since rods and cones only respond to a change in luminance.[citation needed]
# Pathophysiologic saccades
Saccadic oscillations not filling the normal function are a deviation from a healthy or normal condition.
## Causes
- Nystagmus is characterised by the combination of a smooth pursuit, which usually acts to take the eye off the point of regard, interspersed with the saccadic movement that serves to bring the eye back on target.
- Opsoclonus or ocular flutter, on the other hand, are composed purely of fast-phase saccadic eye movements.
Without the use of objective recording techniques, it may be very difficult to distinguish between these conditions.
# Saccadic masking
It is a common but false belief that during the saccade, no information is passed through the optic nerve to the brain. Whereas low spatial frequencies (the 'fuzzier' parts) are attenuated, higher spatial frequencies (an image's fine details) which would otherwise be blurred out by the eye movement remain unaffected. This phenomenon, known as saccadic masking or saccadic suppression, is known to occur in the time preceding a saccadic eye movement, implying neurological reasons for the effect, rather than simply the image's motion blur.
A person may observe the saccadic masking effect by standing in front of a mirror and looking from one eye to the next (and vice versa). The subject will not experience any movement of the eyes nor any evidence that the optic nerve has momentarily ceased transmitting. Due to saccadic masking, the eye/brain system not only hides the eye movements from the individual but also hides the evidence that anything has been hidden. Of course, a second observer watching the experiment will see the subject's eyes moving back and forth.
# Comparative physiology
Saccades are a widespread phenomenon across animals with image-forming visual systems. They have been observed in animals across three phyla, including animals that do not have a fovea (most vertebrates do not) and animals that cannot move their eyes independently of their head (such as insects).[3] Therefore, while saccades serve in humans and other primates to increase the effective visual resolution of a scene, there must be additional reasons for the behavior. The most frequently suggested of these reasons is to avoid blurring of the image, which would occur if the response time of a photoreceptor is longer than the time a given portion of the image is stimulating that photoreceptor as the image drifts across the eye.
In birds, saccadic eye movements serve a further function. The avian retina is highly developed. It is thicker than the mammalian retina and has a higher metabolic activity, but it lacks proper vasculature. Therefore, the retinal cells must obtain nutrients via diffusion through the choroid and from the vitreous humor. The pecten is a specialised structure in the avian retina. It is a highly vascular structure that projects into the vitreous humor. Experimentally, it has been shown that during saccadic eye oscillations (which occupy up to 12% of avian viewing time), the pecten acts as an agitator, propelling perfusate towards the retina. Thus, in birds, saccadic eye movements appear to be important in retinal nutrition and respiration.[4] | https://www.wikidoc.org/index.php/Saccade | |
de3847ffe708cee3bc3d4fe20f591395577ee03d | wikidoc | Sucrose | Sucrose
Sucrose (common name: table sugar, also called saccharose) is a disaccharide (glucose + fructose) with the molecular formula C12H22O11. Its systematic name is α-D-glucopyranosyl-(1→2)-β-D-fructofuranose. It is best known for its role in human nutrition and is formed by plants but not by other organisms.
# Physical and chemical properties
Pure sucrose is most often prepared as a fine, white, odorless crystalline powder with a pleasing, sweet taste; the common table sugar. Large crystals are sometimes precipitated from water solutions of sucrose onto a string (or other nucleation surface) to form rock candy, a confection.
Like other carbohydrates, sucrose has a hydrogen to oxygen ratio of 2:1. It consists of two monosaccharides, α-glucose and fructose, joined by a glycosidic bond between carbon atom 1 of the glucose unit and carbon atom 2 of the fructose unit. What is notable about sucrose is that unlike most polysaccharides, the glycosidic bond is formed between the reducing ends of both glucose and fructose, and not between the reducing end of one and the nonreducing end of the other. The effect of this inhibits further bonding to other saccharide units. Since it contains no free anomeric carbon atom, it is classified as a nonreducing sugar.
Sucrose melts and decomposes at 186 °C to form caramel, and when combusted produces carbon, carbon dioxide, and water. Water breaks down sucrose by hydrolysis, however the process is so gradual that it could sit in solution for years with negligible change. If the enzyme sucrase is added however, the reaction will proceed rapidly.
Reacting sucrose with sulfuric acid dehydrates the sucrose and forms elemental carbon, as demonstrated in the following equation:
# Commercial production and use
Sucrose is the most common food sweetener, although it has been replaced in American industrial food production by other sweeteners such as fructose syrups or combinations of functional ingredients and high intensity sweeteners. This is due to the subsidization of corn in the United States, which has led to a vast surplus. Combined with sugar tariffs, this has driven the price of corn syrup far below that of sugar.
Sucrose is the most important sugar in plants, and can be found in the phloem sap. It is generally extracted from sugar cane or sugar beet and then purified and crystallized. Other (minor) commercial sources are sweet sorghum and sugar maples.
Sucrose is ubiquitous in food preparations due to both its sweetness and its functional properties; it is important to the structure of many foods including biscuits and cookies, candy canes, ice cream and sorbets, and also assists in the preservation of foods. As such it is common in many processed and so-called “junk foods.”
# Sugar as a macronutrient
In mammals, sucrose is very readily digested in the stomach into its component sugars, by acidic hydrolysis. This step is performed by a glycoside hydrolase, which catalyzes the hydrolysis of sucrose to the monosaccharides glucose and fructose. Glucose and fructose are rapidly absorbed into the bloodstream in the small intestine. Undigested sucrose passing into the intestine is also broken down by sucrase or isomaltase glycoside hydrolases, which are located in the membrane of the microvilli lining the duodenum. These products are also transferred rapidly into the bloodstream.
Sucrose is digested by the enzyme invertase in bacteria and some animals.
Acidic hydrolysis can be used in laboratories to achieve the hydrolysis of sucrose into glucose and fructose.
## In human nutrition
Sucrose is an easily assimilated macronutrient that provides a quick source of energy to the body, provoking a rapid rise in blood glucose upon ingestion. However, pure sucrose is not normally part of a human diet balanced for good nutrition, although it may be included sparingly to make certain foods more palatable.
Overconsumption of sucrose has been linked with some adverse health effects. The most common is dental caries or tooth decay, in which oral bacteria convert sugars (including sucrose) from food into acids that attack tooth enamel. Sucrose, as a pure carbohydrate, has an energy content of 4 kilocalories per gram (or 17 kilojoules per gram). When a large amount of foods that contain a high percentage of sucrose is consumed, beneficial nutrients can be displaced from the diet, which can contribute to an increased risk for chronic disease. It has been suggested that sucrose-containing drinks may be linked to the development of obesity and insulin resistance.
The rapidity with which sucrose raises blood glucose can cause problems for people suffering from defects in glucose metabolism, such as persons with hypoglycemia or diabetes mellitus. Sucrose can contribute to development of the metabolic syndrome. In an experiment with rats that were fed a diet one-third of which was sucrose, the sucrose first elevated blood levels of triglycerides, which induced visceral fat and ultimately resulted in insulin resistance. Another study found that rats fed sucrose-rich diets developed high triglycerides, hyperglycemia, and insulin resistance. | Sucrose
Template:Chembox new
Sucrose (common name: table sugar, also called saccharose) is a disaccharide (glucose + fructose) with the molecular formula C12H22O11. Its systematic name is α-D-glucopyranosyl-(1→2)-β-D-fructofuranose. It is best known for its role in human nutrition and is formed by plants but not by other organisms.
# Physical and chemical properties
Pure sucrose is most often prepared as a fine, white, odorless crystalline powder with a pleasing, sweet taste; the common table sugar. Large crystals are sometimes precipitated from water solutions of sucrose onto a string (or other nucleation surface) to form rock candy, a confection.
Like other carbohydrates, sucrose has a hydrogen to oxygen ratio of 2:1. It consists of two monosaccharides, α-glucose and fructose, joined by a glycosidic bond between carbon atom 1 of the glucose unit and carbon atom 2 of the fructose unit. What is notable about sucrose is that unlike most polysaccharides, the glycosidic bond is formed between the reducing ends of both glucose and fructose, and not between the reducing end of one and the nonreducing end of the other. The effect of this inhibits further bonding to other saccharide units. Since it contains no free anomeric carbon atom, it is classified as a nonreducing sugar.
Sucrose melts and decomposes at 186 °C to form caramel, and when combusted produces carbon, carbon dioxide, and water. Water breaks down sucrose by hydrolysis, however the process is so gradual that it could sit in solution for years with negligible change. If the enzyme sucrase is added however, the reaction will proceed rapidly.
Reacting sucrose with sulfuric acid dehydrates the sucrose and forms elemental carbon, as demonstrated in the following equation:
# Commercial production and use
Sucrose is the most common food sweetener, although it has been replaced in American industrial food production by other sweeteners such as fructose syrups or combinations of functional ingredients and high intensity sweeteners. This is due to the subsidization of corn in the United States, which has led to a vast surplus. Combined with sugar tariffs, this has driven the price of corn syrup far below that of sugar.
Sucrose is the most important sugar in plants, and can be found in the phloem sap. It is generally extracted from sugar cane or sugar beet and then purified and crystallized. Other (minor) commercial sources are sweet sorghum and sugar maples.
Sucrose is ubiquitous in food preparations due to both its sweetness and its functional properties; it is important to the structure of many foods including biscuits and cookies, candy canes, ice cream and sorbets, and also assists in the preservation of foods. As such it is common in many processed and so-called “junk foods.”
# Sugar as a macronutrient
In mammals, sucrose is very readily digested in the stomach into its component sugars, by acidic hydrolysis. This step is performed by a glycoside hydrolase, which catalyzes the hydrolysis of sucrose to the monosaccharides glucose and fructose. Glucose and fructose are rapidly absorbed into the bloodstream in the small intestine. Undigested sucrose passing into the intestine is also broken down by sucrase or isomaltase glycoside hydrolases, which are located in the membrane of the microvilli lining the duodenum. These products are also transferred rapidly into the bloodstream.
Sucrose is digested by the enzyme invertase in bacteria and some animals.
Acidic hydrolysis can be used in laboratories to achieve the hydrolysis of sucrose into glucose and fructose.
## In human nutrition
Sucrose is an easily assimilated macronutrient that provides a quick source of energy to the body, provoking a rapid rise in blood glucose upon ingestion. However, pure sucrose is not normally part of a human diet balanced for good nutrition, although it may be included sparingly to make certain foods more palatable.
Overconsumption of sucrose has been linked with some adverse health effects. The most common is dental caries or tooth decay, in which oral bacteria convert sugars (including sucrose) from food into acids that attack tooth enamel. Sucrose, as a pure carbohydrate, has an energy content of 4 kilocalories per gram (or 17 kilojoules per gram). When a large amount of foods that contain a high percentage of sucrose is consumed, beneficial nutrients can be displaced from the diet, which can contribute to an increased risk for chronic disease. It has been suggested that sucrose-containing drinks may be linked to the development of obesity and insulin resistance.[1]
The rapidity with which sucrose raises blood glucose can cause problems for people suffering from defects in glucose metabolism, such as persons with hypoglycemia or diabetes mellitus. Sucrose can contribute to development of the metabolic syndrome.[2] In an experiment with rats that were fed a diet one-third of which was sucrose, the sucrose first elevated blood levels of triglycerides, which induced visceral fat and ultimately resulted in insulin resistance.[3] Another study found that rats fed sucrose-rich diets developed high triglycerides, hyperglycemia, and insulin resistance.[4] | https://www.wikidoc.org/index.php/Saccharose | |
858a9ffc006a94bf2834fc817b57c6cc2d31ab1c | wikidoc | Sadness | Sadness
# Overview
Sadness is a mood characterized by feelings of disadvantage and loss. When sad, people often become quiet, less energetic and withdrawn. Sadness is considered to be the opposite of happiness, and is similar to the emotions of sorrow, grief, misery and melancholy. The philosopher Baruch Spinoza defined sadness as the “transfer of a person from a large perfection to a smaller one.”
Sadness is a temporary lowering of mood ('feeling blue'), whereas clinical depression is characterized by a persistent and intense lowered mood, as well as disruption to one's ability to function in day to day matters.
# Sadness and the accuracy of evaluation
Evidence presented by Forgas (1992, 1994) suggests that our mood has an influence on how accurately we evaluate each other. The effect on our accuracy might be a result of faulty information processing where a person may take his current mood as a source of information. He would then use this biased information as a bases for his evaluation. For instance, happy people are inclined to evaluate others in a positive way, and sad people are inclined to evaluate people in a negative way.
Sad people have been found to be less accurate than happy people in their evaluations, as well as taking a longer period of time for the evaluation. Several explanations for this have been postulated:
- Functional (Forgas, 1998) – Mood indicates a social situation that in turn enables specific behaviors. Therefore, happiness indicates a positive social situation in which the behavior is more relaxed. In contrast, sadness indicates a dangerous social situation that requires more attention and for that reason requires greater information processing.
- Motivational (Isen, 1984) -People in a positive mood avoid deep information processing that may cause them to doubt the positive situation they are in. In contrast, people in a sad mood strive to change the negative situation they are in.
- The ability to process information is influenced by mood (Isen, 1987) - Happy people require less cognitional resources for deep and precise information processing than sad people. One study showed that resource blocking through use of distractions prevented people from deep and precise information processing and raised the comparative effectiveness of people in a sad mood.
# Sadness and status
Sadness may affect a person's social standing.
Studies have found that when people recognize an expressed emotion, they tend to attribute additional characteristics to the person expressing that emotion (Halo effect). A happy person, therefore is perceived warmly whereas a sad person is perceived as weak and lacking ability and an angry person is perceived as powerful and dominant.(Keltner, 1997).
Tiedens's study explored whether people provide power to people they like or rather to people they perceive as powerful. The study, which examined social position in political, business and job interview situations, found that people prefer to give status position and power to an angry leader rather than to a sad one. People tend to give power to those perceived as powerful instead of to those whom they like. For example, in the business world, a positive statistical correlation was found between sadness and the extent of a person's social contribution, however angry people were perceived more deserving of status and promotion. Similarly, in the job interviews, angry people were perceived as more suitable for promotion and high salary than sad people. | Sadness
Template:Emotion
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Sadness is a mood characterized by feelings of disadvantage and loss. When sad, people often become quiet, less energetic and withdrawn. Sadness is considered to be the opposite of happiness, and is similar to the emotions of sorrow, grief, misery and melancholy. The philosopher Baruch Spinoza defined sadness as the “transfer of a person from a large perfection to a smaller one.”
Sadness is a temporary lowering of mood ('feeling blue'), whereas clinical depression is characterized by a persistent and intense lowered mood, as well as disruption to one's ability to function in day to day matters.
# Sadness and the accuracy of evaluation
Evidence presented by Forgas (1992, 1994)[1] suggests that our mood has an influence on how accurately we evaluate each other. The effect on our accuracy might be a result of faulty information processing where a person may take his current mood as a source of information. He would then use this biased information as a bases for his evaluation.[2] For instance, happy people are inclined to evaluate others in a positive way, and sad people are inclined to evaluate people in a negative way.
Sad people have been found to be less accurate than happy people in their evaluations, as well as taking a longer period of time for the evaluation. [3] Several explanations for this have been postulated:
- Functional (Forgas, 1998) – Mood indicates a social situation that in turn enables specific behaviors. Therefore, happiness indicates a positive social situation in which the behavior is more relaxed. In contrast, sadness indicates a dangerous social situation that requires more attention and for that reason requires greater information processing.[4] [5]
- Motivational (Isen, 1984) -People in a positive mood avoid deep information processing that may cause them to doubt the positive situation they are in. In contrast, people in a sad mood strive to change the negative situation they are in.
- The ability to process information is influenced by mood (Isen, 1987) [6]- Happy people require less cognitional resources for deep and precise information processing than sad people. One study showed that resource blocking through use of distractions prevented people from deep and precise information processing and raised the comparative effectiveness of people in a sad mood.[3]
# Sadness and status
Sadness may affect a person's social standing.
Studies have found that when people recognize an expressed emotion, they tend to attribute additional characteristics to the person expressing that emotion (Halo effect). A happy person, therefore is perceived warmly whereas a sad person is perceived as weak and lacking ability[7] and an angry person is perceived as powerful and dominant.(Keltner, 1997).
Tiedens's [8] study explored whether people provide power to people they like or rather to people they perceive as powerful. The study, which examined social position in political, business and job interview situations, found that people prefer to give status position and power to an angry leader rather than to a sad one. People tend to give power to those perceived as powerful instead of to those whom they like. For example, in the business world, a positive statistical correlation was found between sadness and the extent of a person's social contribution, however angry people were perceived more deserving of status and promotion. Similarly, in the job interviews, angry people were perceived as more suitable for promotion and high salary than sad people. | https://www.wikidoc.org/index.php/Sadness | |
53657ea75a3f27432c7743a4e4e8d85c25a63c25 | wikidoc | Saffron | Saffron
Saffron (IPA: Template:IPA) is a spice derived from the flower of the saffron crocus (Crocus sativus), a species of crocus in the family Iridaceae. The flower has three stigmas, which are the distal ends of the plant's carpels. Together with its style, the stalk connecting the stigmas to the rest of the plant, these components are often dried and used in cooking as a seasoning and colouring agent. Saffron, which has for decades been the world's most expensive spice by weight, is native to Southwest Asia. It was first cultivated in the vicinity of Greece.
Saffron is characterised by a bitter taste and an iodoform- or hay-like fragrance; these are caused by the chemicals picrocrocin and safranal. It also contains a carotenoid dye, crocin, that gives food a rich golden-yellow hue. These traits make saffron a much-sought ingredient in many foods worldwide. Saffron also has medicinal applications.
The word saffron originated from the 12th-century Old French term safran, which derives from the Latin word safranum. Safranum is also related to the Italian zafferano and Spanish azafrán. Safranum comes from the Arabic word Template:ArabDIN (Template:Rtl-lang), which means "yellow," via the paronymous Template:ArabDIN (Template:Rtl-lang), the name of the spice in Arabic.
# Biology
The domesticated saffron crocus C. sativus is an autumn-flowering perennial plant unknown in the wild, and is a sterile triploid mutant of the eastern Mediterranean autumn-flowering Crocus cartwrightianus. According to botanical research, C. cartwrightianus originated in Crete, not—as was once generally believed—in Central Asia. The saffron crocus resulted when C. cartwrightianus was subjected to extensive artificial selection by growers who desired elongated stigmas. Being sterile, the saffron crocus's purple flowers fail to produce viable seeds—thus, reproduction is dependent on human assistance: the corms (underground bulb-like starch-storing organs) must be manually dug up, broken apart, and replanted. A corm survives for only one season, reproducing via division into up to ten "cormlets" that eventually give rise to new plants. The corms are small brown globules up to 4.5 cm in diameter and are shrouded in a dense mat of parallel fibers.
After a period of aestivation in summer, five to eleven narrow and nearly vertical green leaves—growing up to 40 cm in length—emerge from the ground. In autumn, purple buds appear. Only in October, after most other flowering plants have released their seeds, does it develop its brilliantly hued flowers, ranging from a light pastel shade of lilac to a darker and more striated mauve. Upon flowering, it averages less than 30 cm in height. Inside each flower is a three-pronged style; in turn, each prong terminates with a crimson stigma 25–30 mm in length.
# Cultivation
The saffron crocus thrives in climates similar to that of the Mediterranean maquis or the North American chaparral, where hot, dry summer breezes blow across arid and semi-arid lands. Nevertheless, the plant can tolerate cold winters, surviving frosts as cold as −10 °C and short periods of snow cover. However, if not grown in wet environments like Kashmir (where rainfall averages 1000–1500 mm annually), irrigation is needed—this is true in the saffron-growing regions of Greece (500 mm of rainfall annually) and Spain (400 mm). Rainfall timing is also key: generous spring rains followed by relatively dry summers are optimal. In addition, rainfall occurring immediately prior to flowering also boosts saffron yields; nevertheless, rainy or cold weather occurring during flowering promotes disease, thereby reducing yields. Persistently damp and hot conditions also harm yields, as do the digging actions of rabbits, rats, and birds. Parasites such as nematodes, leaf rusts, and corm rot also pose significant threats.
Saffron plants grow best in strong and direct sunlight, and fare poorly in shady conditions. Thus, planting is best done in fields that slope towards the sunlight (i.e. south-sloping in the Northern Hemisphere), maximizing the crocuses' sun exposure. In the Northern Hemisphere, planting is mostly done in June, with corms planted some 7–15 cm deep. Planting depth and corm spacing—along with climate—are both critical factors impacting plant yields. Thus, mother corms planted more deeply yield higher-quality saffron, although they produce fewer flower buds and daughter corms. With such knowledge, Italian growers have found that planting corms Template:Cm to in deep and in rows spaced 2–3 cm apart optimizes threads yields, whereas planting depths of 8–10 cm optimizes flower and corm production. Meanwhile, Greek, Moroccan, and Spanish growers have devised different depths and spacings to suit their own climates.
Saffron crocuses grow best in friable, loose, low-density, well-watered, and well-drained clay-calcareous soils with high organic content. Raised beds are traditionally used to promote good drainage. Historically, soil organic content was boosted via application of some 20–30 tonnes of manure per hectare. Afterwards—and with no further manure application—corms were planted. After a period of dormancy through the summer, the corms send up their narrow leaves and begin to bud in early autumn. Only in mid-autumn do the plants begin to flower. Harvesting of flowers is by necessity a speedy affair: after their flowering at dawn, flowers quickly wilt as the day passes. Furthermore, saffron crocuses bloom within a narrow window spanning one or two weeks. Approximately 150 flowers yield 1 g of dry saffron threads; to produce 12 g of dried saffron (72 g freshly harvested), 1 kg of flowers are needed (1 lb for 0.2 oz of dried saffron). On average, one freshly picked flower yields 0.03 g of fresh saffron, or 0.007 g of dried saffron.
# Chemistry
Saffron contains more than 150 volatile and aroma-yielding compounds. It also has many nonvolatile active components, many of which are carotenoids, including zeaxanthin, lycopene, and various α- and β-carotenes. However, saffron's golden yellow-orange colour is primarily the result of α-crocin. This crocin is trans-crocetin di-(β-D-gentiobiosyl) ester (systematic (IUPAC) name: 8,8-diapo-8,8-carotenoic acid). This means that the crocin underlying saffron's aroma is a digentiobiose ester of the carotenoid crocetin. Crocins themselves are a series of hydrophilic carotenoids that are either monoglycosyl or diglycosyl polyene esters of crocetin. Meanwhile, crocetin is a conjugated polyene dicarboxylic acid that is hydrophobic, and thus oil-soluble. When crocetin is esterified with two water-soluble gentiobioses (which are sugars), a product results that is itself water-soluble. The resultant α-crocin is a carotenoid pigment that may comprise more than 10% of dry saffron's mass. The two esterified gentiobioses make α-crocin ideal for colouring water-based (non-fatty) foods such as rice dishes.
The bitter glucoside picrocrocin is responsible for saffron's flavour. Picrocrocin (chemical formula: C16H26O7; systematic name: 4-(β-D-glucopyranosyloxy)-2,6,6- trimethylcyclohex-1-ene-1-carboxaldehyde) is a union of an aldehyde sub-element known as safranal (systematic name: 2,6,6-trimethylcyclohexa-1,3-dien-1- carboxaldehyde) and a carbohydrate. It has insecticidal and pesticidal properties, and may comprise up to 4% of dry saffron. Significantly, picrocrocin is a truncated version (produced via oxidative cleavage) of the carotenoid zeaxanthin and is the glycoside of the terpene aldehyde safranal. The reddish-coloured zeaxanthin is, incidentally, one of the carotenoids naturally present within the retina of the human eye.
When saffron is dried after its harvest, the heat, combined with enzymatic action, splits picrocrocin to yield D-glucose and a free safranal molecule. Safranal, a volatile oil, gives saffron much of its distinctive aroma. Safranal is less bitter than picrocrocin and may comprise up to 70% of dry saffron's volatile fraction in some samples. A second element underlying saffron's aroma is 2-hydroxy-4,4,6-trimethyl-2,5-cyclohexadien-1-one, the scent of which has been described as "saffron, dried hay like". Chemists found this to be the most powerful contributor to saffron's fragrance despite its being present in a lesser quantity than safranal. Dry saffron is highly sensitive to fluctuating pH levels, and rapidly breaks down chemically in the presence of light and oxidizing agents. It must therefore be stored away in air-tight containers in order to minimise contact with atmospheric oxygen. Saffron is somewhat more resistant to heat.
# History
The history of saffron cultivation reaches back more than 3,000 years. The wild precursor of domesticated saffron crocus was Crocus cartwrightianus. Human cultivators bred wild specimens by selecting for unusually long stigmas. Thus, a sterile mutant form of C. cartwrightianus, C. sativus, emerged in late Bronze Age Crete. Experts believe saffron was first documented in a 7th century BC Assyrian botanical reference compiled under Ashurbanipal. Since then, documentation of saffron's use over the span of 4,000 years in the treatment of some 90 illnesses has been uncovered. Saffron has been used as a spice and medicine in the Mediterranean region since then, with usage and cultivation slowly spreading to other parts of Eurasia as well as North Africa and North America. In the last several decades, saffron cultivation has spread to Oceania.
## Mediterranean
Minoans portrayed saffron in their palace frescoes by 1500–1600 BC, showing saffron's use as a therapeutic drug. Later, Greek legends told of sea voyages to Cilicia. There, adventurers hoped to procure what they believed was the world's most valuable saffron. Another legend tells of Crocus and Smilax, whereby Crocus is bewitched and transformed into the original saffron crocus. Ancient Mediterranean peoples—including perfumers in Egypt, physicians in Gaza, townspeople in Rhodes, and the Greek hetaerae courtesans—used saffron in their perfumes, ointments, potpourris, mascaras, divine offerings, and medical treatments.
In late Hellenistic Egypt, Cleopatra used saffron in her baths so that lovemaking would be more pleasurable. Egyptian healers used saffron as a treatment for all varieties of gastrointestinal ailments. Saffron was also used as a fabric dye in such Levant cities as Sidon and Tyre. Aulus Cornelius Celsus prescribes saffron in medicines for wounds, cough, colic, and scabies, and in the mithridatium. Such was the Romans' love of saffron that Roman colonists took their saffron with them when they settled in southern Gaul, where it was extensively cultivated until Rome's fall. Competing theories state that saffron only returned to France with 8th century AD Moors or with the Avignon papacy in the 14th century AD.
## Asia
Saffron-based pigments have been found in 50,000 year-old depictions of prehistoric beasts in what is today Iraq. Later, the Sumerians used wild-growing saffron in their remedies and magical potions. Saffron was thus an article of long-distance trade before the Minoan palace culture's 2nd millennium BC peak. Saffron was also honored in the Hebrew Song of Solomon. Ancient Persians cultivated Persian saffron (Crocus sativus 'Hausknechtii') in Derbena, Isfahan, and Khorasan by the 10th century BC. At such sites, saffron threads were woven into textiles, ritually offered to divinities, and used in dyes, perfumes, medicines, and body washes. Thus, saffron threads would be scattered across beds and mixed into hot teas as a curative for bouts of melancholy. Non-Persians also feared the Persians' usage of saffron as a drugging agent and aphrodisiac. During his Asian campaigns, Alexander the Great used Persian saffron in his infusions, rice, and baths as a curative for battle wounds. Alexander's troops mimicked the practice and brought saffron-bathing back to Greece.
Theories explaining saffron's arrival in South Asia conflict. Traditional Kashmiri and Chinese accounts date its arrival anywhere between 900–2500 years ago. Meanwhile, historians studying ancient Persian records date the arrival to sometime prior to 500 BC, attributing it to either Persian transplantation of saffron corms to stock new gardens and parks or to a Persian invasion and colonization of Kashmir. Phoenicians then marketed Kashmiri saffron as a dye and a treatment for melancholy. From there, saffron use in foods and dyes spread throughout South Asia. For example, Buddhist monks in India adopted saffron-coloured robes after the Buddha Siddhartha Gautama's death.
Some historians believe that saffron first came to China with Mongol invaders by way of Persia. On the other hand, saffron is mentioned in ancient Chinese medical texts, including the forty-volume Shennong Bencaojing (神農本草經—"Shennong's Great Herbal", also known as Pen Ts'ao or Pun Tsao) pharmacopoeia, a tome dating from 200–300 BC. Traditionally attributed to the legendary Yan ("Fire") Emperor (炎帝) Shennong, it documents 252 phytochemical-based medical treatments for various disorders. Yet around the 3rd century AD, the Chinese were referring to saffron as having a Kashmiri provenance. For example, Wan Zhen, a Chinese medical expert, reported that "he habitat of saffron is in Kashmir, where people grow it principally to offer it to the Buddha." Wan also reflected on how saffron was used in his time: "The flower withers after a few days, and then the saffron is obtained. It is valued for its uniform yellow colour. It can be used to aromatise wine."Template:Inote
## Europe
In Europe, saffron cultivation declined steeply following the Roman Empire's fall. Saffron was reintroduced when Moorish civilization spread to Spain, France, and Italy. During the 14th century Black Death, demand for saffron-based medicine skyrocketed, and much saffron had to be imported via Venetian and Genoan ships from southern and Mediterranean lands such as Rhodes. The theft of one such shipment by noblemen sparked the fourteen-week long "Saffron War". The conflict and resulting fear of rampant saffron piracy spurred significant saffron cultivation in Basel, which grew prosperous. Cultivation and trade then spread to Nuremberg, where epidemic levels of saffron adulteration brought on the Safranschou code, under which saffron adulterers were fined, imprisoned, and executed. Soon after, saffron cultivation spread throughout England, especially Norfolk and Suffolk. The Essex town of Saffron Walden, named for its new specialty crop, emerged as England's prime saffron growing and trading center. However, an influx of more exotic spices such as chocolate, coffee, tea, and vanilla from newly contacted Eastern and overseas countries caused European cultivation and usage of saffron to decline. Only in southern France, Italy, and Spain, did significant cultivation endure.
Europeans brought saffron to the Americas when immigrant members of the Schwenkfelder Church left Europe with a trunk containing saffron corms; indeed, many Schwenkfelders had widely grown saffron in Europe. By 1730, the Pennsylvania Dutch were cultivating saffron throughout eastern Pennsylvania. Spanish colonies in the Caribbean bought large amounts of this new American saffron, and high demand ensured that saffron's list price on the Philadelphia commodities exchange was set equal to that of gold. The trade with the Caribbean later collapsed in the aftermath of the War of 1812, when many saffron-transporting merchant vessels were destroyed. Yet the Pennsylvania Dutch continued to grow lesser amounts of saffron for local trade and use in their cakes, noodles, and chicken or trout dishes. American saffron cultivation survived into modern times mainly in Lancaster County, Pennsylvania.
# Trade and use
Saffron's aroma is often described by connoisseurs as reminiscent of metallic honey with grassy or hay-like notes, while its taste has been noted also as hay-like and somewhat bitter. Saffron also contributes a luminous yellow-orange colouring to foods. Saffron is widely used in Persian, Arab, Central Asian, European, Indian, Iranian, Moroccan and Cornish cuisines. Confectionaries and liquors also often include saffron. Common saffron substitutes include safflower (Carthamus tinctorius, which is often sold as "Portuguese saffron" or "assafroa") and turmeric (Curcuma longa). Medicinally, saffron has a long history as part of traditional healing; modern medicine has also discovered saffron as having anticarcinogenic (cancer-suppressing), anti-mutagenic (mutation-preventing), immunomodulating, and antioxidant-like properties. Saffron has also been used as a fabric dye, particularly in China and India, and in perfumery.
Most saffron is grown in a belt of land ranging from the Mediterranean in the west to Kashmir in the east. Annually, around 300 tonnes of saffron are produced worldwide. Iran, Spain, India, Greece, Azerbaijan, Morocco, and Italy (in decreasing order of production) are the major producers of saffron. A pound of dry saffron (0.45 kg) requires 50,000–75,000 flowers, the equivalent of a football field's area of cultivation. Some forty hours of frenetic day-and-night labour are needed to pick 150,000 flowers. Upon extraction, stigmas are dried quickly and (preferably) sealed in airtight containers. Saffron prices at wholesale and retail rates range from US$500/pound to US$5,000/pound (US$1100–US$11,000 per kilogram)—equivalent to £2,500/€3,500 per pound or £5,500/€7,500 per kilo. In Western countries, the average retail price is $1,000/£500/€700 per pound (US$2200/£1100/€1550 per kilogram). Between 70,000 and 200,000 threads comprise a pound. Vivid crimson colouring, slight moistness, elasticity, recent harvest date, and lack of broken-off thread debris are all traits of fresh saffron.
# Cultivars
Several saffron cultivars are grown worldwide. Spain's varieties, including the tradenames 'Spanish Superior' and 'Creme', are generally mellower in colour, flavour, and aroma; they are graded by government-imposed standards. Italian varieties are more potent, while the most intense varieties tend to be Macedonian Greek, Iranian, and Indian in origin. Westerners may face significant obstacles in obtaining saffron from India. For example, India has banned the export of high-grade saffron abroad. Aside from these, various "boutique" crops are available from New Zealand, France, Switzerland, England, the United States, and other countries, some organically grown. In the U.S., Pennsylvania Dutch saffron—known for its earthy notes—is marketed in small quantities.
Consumers regard certain cultivars as "premium" quality. The "Aquila" saffron (zafferano dell'Aquila)—defined by high safranal and crocin content, shape, unusually pungent aroma, and intense colour—is grown exclusively on eight hectares in the Navelli Valley of Italy's Abruzzo region, near L'Aquila. It was first introduced to Italy by a Dominican monk from Inquisition-era Spain. But in Italy the biggest saffron cultivation, for quality and quantity, is in San Gavino Monreale, Sardinia. There, saffron is grown on 40 hectares (60% of Italian production); it also has very high crocin, picrocrocin, and safranal content. Another is the Kashmiri "Mongra" or "Lacha" saffron (Crocus sativus 'Cashmirianus'), which is among the most difficult for consumers to obtain. Repeated droughts, blights, and crop failures in Kashmir, combined with an Indian export ban, contribute to its high prices. Kashmiri saffron is recognisable by its extremely dark maroon-purple hue, among the world's darkest, which suggests the saffron's strong flavour, aroma, and colourative effect.
# Grades
Saffron types are graded by quality according to laboratory measurements of such characteristics as crocin (colour), picrocrocin (taste), and safranal (fragrance) content. Other metrics include floral waste content (i.e. the saffron spice sample's non-stigma floral content) and measurements of other extraneous matter such as inorganic material ("ash"). A uniform set of international standards in saffron grading was established by the International Organization for Standardization, which is an international federation of national standards bodies. Namely, ISO 3632 deals exclusively with saffron. It establishes four empirical grades of colour intensity: IV (poorest), III, II, and I (finest quality). Saffron samples are then assigned to one of these grades by gauging the spice's crocin content, which is revealed by measurements of crocin-specific spectroscopic absorbance. Absorbance is defined as A_\lambda = -\log(I/I_0), with A_\lambda as absorbance (Beer-Lambert law). It is a measure of a given substance's transparency (I/I_0, the ratio of light intensity passing through sample to that of the incident light) to a given wavelength of light.
For saffron, absorbance is determined for the crocin-specific photon wavelength of 440 nm in a given dry sample of spice. Higher absorbances at this wavelength imply greater crocin concentration, and thus a greater colourative intensity. These data are measured through spectrophotometry reports at certified testing laboratories worldwide. These colour grades proceed from grades with absorbances lower than 80 (for all category IV saffron) up to 190 or greater (for category I). The world's finest samples (the selected most red-maroon tips of stigmas picked from the finest flowers) receive absorbance scores in excess of 250. Market prices for saffron types follow directly from these ISO scores. However, many growers, traders, and consumers reject such lab test numbers. They prefer a more holistic method of sampling batches of thread for taste, aroma, pliability, and other traits in a fashion similar to that practiced by practised wine tasters.
Despite such attempts at quality control and standardisation, an extensive history of saffron adulteration—particularly among the cheapest grades—continues into modern times. Adulteration was first documented in Europe's Middle Ages, when those found selling adulterated saffron were executed under the Safranschou code. Typical methods include mixing in extraneous substances like beet, pomegranate fibers, red-dyed silk fibers, or the saffron crocus's tasteless and odorless yellow stamens. Other methods included dousing saffron fibers with viscid substances like honey or vegetable oil. However, powdered saffron is more prone to adulteration, with turmeric, paprika, and other powders used as diluting fillers. Adulteration can also consist of selling mislabeled mixes of different saffron grades. Thus, in India, high-grade Kashmiri saffron is often sold mixed with cheaper Iranian imports; these mixes are then marketed as pure Kashmiri saffron, a development that has cost Kashmiri growers much of their income.
# Notes
- ↑ Rau 1969, p. 53.
- ↑ Jump up to: 2.0 2.1 2.2 Hill 2004, p. 272.
- ↑ Grigg 1974, p. 287.
- ↑ Jump up to: 4.0 4.1 4.2 McGee 2004, p. 422.
- ↑ Jump up to: 5.0 5.1 McGee 2004, p. 423.
- ↑ Jump up to: 6.0 6.1 6.2 6.3 Katzer 2001.
- ↑ Harper 2001.
- ↑ Jump up to: 8.0 8.1 8.2 8.3 8.4 Deo 2003, p. 1.
- ↑ Willard 2001, p. 3.
- ↑ DPIWE 2005.
- ↑ Jump up to: 11.0 11.1 Willard 2001, pp. 2–3.
- ↑ Jump up to: 12.0 12.1 Deo 2003, p. 2.
- ↑ Jump up to: 13.0 13.1 13.2 Deo 2003, p. 3.
- ↑ Willard 2001, pp. 3–4.
- ↑ Willard 2001, p. 4.
- ↑ Jump up to: 16.0 16.1 Deo 2003, p. 4.
- ↑ Jump up to: 17.0 17.1 17.2 17.3 17.4 Abdullaev 2002, p. 1.
- ↑ Jump up to: 18.0 18.1 Leffingwell 2001, p. 1.
- ↑ Dharmananda 2005.
- ↑ Jump up to: 20.0 20.1 Leffingwell 2001, p. 3.
- ↑ Goyns 1999, p. 1.
- ↑ Jump up to: 22.0 22.1 Honan 2004.
- ↑ Ferrence 2004, p. 1.
- ↑ Jump up to: 24.0 24.1 24.2 Willard 2001, p. 2.
- ↑ Willard 2001, p. 58.
- ↑ Jump up to: 26.0 26.1 26.2 26.3 Willard 2001, p. 41.
- ↑ Willard 2001, p. 55.
- ↑ Willard 2001, pp. 34–35.
- ↑ Willard 2001, p. 59.
- ↑ Celsus, de Medicina, ca. 30 AD, transl. Loeb Classical Library Edition, 1935
- ↑ Willard 2001, p. 63.
- ↑ Humphries 1998, p. 20.
- ↑ Willard 2001, p. 12.
- ↑ Humphries 1998, p. 19.
- ↑ Willard 2001, pp. 17–18.
- ↑ Willard 2001, pp. 54–55.
- ↑ Lak 1998b.
- ↑ Fotedar 1998–1999, p. 128.
- ↑ Dalby 2003, p. 256.
- ↑ Jump up to: 40.0 40.1 40.2 Tarvand 2005.
- ↑ Fletcher 2005, p. 11.
- ↑ Hayes 2001, p. 6.
- ↑ Shen-Nong Limited 2005.
- ↑ Willard 2001, p. 70.
- ↑ Jump up to: 45.0 45.1 Willard 2001, p. 99.
- ↑ Willard 2001, p. 101.
- ↑ Willard 2001, pp. 103–104.
- ↑ Willard 2001, p. 117.
- ↑ Willard 2001, pp. 132–133.
- ↑ Willard 2001, p. 133.
- ↑ Jump up to: 51.0 51.1 51.2 Willard 2001, p. 143.
- ↑ Willard 2001, p. 138.
- ↑ Willard 2001, pp. 138–139.
- ↑ Willard 2001, pp. 142–146.
- ↑ Assimopoulou 2005, p. 1.
- ↑ Chang, Kuo & Wang 1964, p. 1.
- ↑ Hill 2004, p. 273.
- ↑ Rau 1969, p. 35.
- ↑ Lak 1998.
- ↑ Goyns 1999, p. 8.
- ↑ Willard 2001, p. 201.
- ↑ Jump up to: 62.0 62.1 Tarvand 2005b.
- ↑ Hill 2004, p. 274.
- ↑ Willard 2001, pp. 102–104.
- ↑ Australian Broadcasting Corporation 2003.
- ↑ Hussain 2005. | Saffron
Saffron (IPA: Template:IPA) is a spice derived from the flower of the saffron crocus (Crocus sativus), a species of crocus in the family Iridaceae. The flower has three stigmas, which are the distal ends of the plant's carpels. Together with its style, the stalk connecting the stigmas to the rest of the plant, these components are often dried and used in cooking as a seasoning and colouring agent. Saffron, which has for decades been the world's most expensive spice by weight,[1][2] is native to Southwest Asia.[2][3] It was first cultivated in the vicinity of Greece.[4]
Saffron is characterised by a bitter taste and an iodoform- or hay-like fragrance; these are caused by the chemicals picrocrocin and safranal.[5][6] It also contains a carotenoid dye, crocin, that gives food a rich golden-yellow hue. These traits make saffron a much-sought ingredient in many foods worldwide. Saffron also has medicinal applications.
The word saffron originated from the 12th-century Old French term safran, which derives from the Latin word safranum. Safranum is also related to the Italian zafferano and Spanish azafrán.[7] Safranum comes from the Arabic word Template:ArabDIN (Template:Rtl-lang), which means "yellow," via the paronymous Template:ArabDIN (Template:Rtl-lang), the name of the spice in Arabic.[6]
# Biology
The domesticated saffron crocus C. sativus is an autumn-flowering perennial plant unknown in the wild, and is a sterile triploid mutant of the eastern Mediterranean autumn-flowering Crocus cartwrightianus.[8] According to botanical research, C. cartwrightianus originated in Crete, not—as was once generally believed—in Central Asia.[6] The saffron crocus resulted when C. cartwrightianus was subjected to extensive artificial selection by growers who desired elongated stigmas. Being sterile, the saffron crocus's purple flowers fail to produce viable seeds—thus, reproduction is dependent on human assistance: the corms (underground bulb-like starch-storing organs) must be manually dug up, broken apart, and replanted. A corm survives for only one season, reproducing via division into up to ten "cormlets" that eventually give rise to new plants.[8] The corms are small brown globules up to 4.5 cm in diameter and are shrouded in a dense mat of parallel fibers.
After a period of aestivation in summer, five to eleven narrow and nearly vertical green leaves—growing up to 40 cm in length—emerge from the ground. In autumn, purple buds appear. Only in October, after most other flowering plants have released their seeds, does it develop its brilliantly hued flowers, ranging from a light pastel shade of lilac to a darker and more striated mauve.[9] Upon flowering, it averages less than 30 cm in height.[10] Inside each flower is a three-pronged style; in turn, each prong terminates with a crimson stigma 25–30 mm in length.[8]
# Cultivation
The saffron crocus thrives in climates similar to that of the Mediterranean maquis or the North American chaparral, where hot, dry summer breezes blow across arid and semi-arid lands. Nevertheless, the plant can tolerate cold winters, surviving frosts as cold as −10 °C and short periods of snow cover.[11][8] However, if not grown in wet environments like Kashmir (where rainfall averages 1000–1500 mm annually), irrigation is needed—this is true in the saffron-growing regions of Greece (500 mm of rainfall annually) and Spain (400 mm). Rainfall timing is also key: generous spring rains followed by relatively dry summers are optimal. In addition, rainfall occurring immediately prior to flowering also boosts saffron yields; nevertheless, rainy or cold weather occurring during flowering promotes disease, thereby reducing yields. Persistently damp and hot conditions also harm yields,[12] as do the digging actions of rabbits, rats, and birds. Parasites such as nematodes, leaf rusts, and corm rot also pose significant threats.[13]
Saffron plants grow best in strong and direct sunlight, and fare poorly in shady conditions. Thus, planting is best done in fields that slope towards the sunlight (i.e. south-sloping in the Northern Hemisphere), maximizing the crocuses' sun exposure. In the Northern Hemisphere, planting is mostly done in June, with corms planted some 7–15 cm deep. Planting depth and corm spacing—along with climate—are both critical factors impacting plant yields. Thus, mother corms planted more deeply yield higher-quality saffron, although they produce fewer flower buds and daughter corms. With such knowledge, Italian growers have found that planting corms Template:Cm to in deep and in rows spaced 2–3 cm apart optimizes threads yields, whereas planting depths of 8–10 cm optimizes flower and corm production. Meanwhile, Greek, Moroccan, and Spanish growers have devised different depths and spacings to suit their own climates.[12]
Saffron crocuses grow best in friable, loose, low-density, well-watered, and well-drained clay-calcareous soils with high organic content. Raised beds are traditionally used to promote good drainage. Historically, soil organic content was boosted via application of some 20–30 tonnes of manure per hectare. Afterwards—and with no further manure application—corms were planted.[13] After a period of dormancy through the summer, the corms send up their narrow leaves and begin to bud in early autumn. Only in mid-autumn do the plants begin to flower. Harvesting of flowers is by necessity a speedy affair: after their flowering at dawn, flowers quickly wilt as the day passes.[14] Furthermore, saffron crocuses bloom within a narrow window spanning one or two weeks.[15] Approximately 150 flowers yield 1 g of dry saffron threads; to produce 12 g of dried saffron (72 g freshly harvested), 1 kg of flowers are needed (1 lb for 0.2 oz of dried saffron). On average, one freshly picked flower yields 0.03 g of fresh saffron, or 0.007 g of dried saffron.[13]
# Chemistry
Saffron contains more than 150 volatile and aroma-yielding compounds. It also has many nonvolatile active components,[17] many of which are carotenoids, including zeaxanthin, lycopene, and various α- and β-carotenes. However, saffron's golden yellow-orange colour is primarily the result of α-crocin. This crocin is trans-crocetin di-(β-D-gentiobiosyl) ester (systematic (IUPAC) name: 8,8-diapo-8,8-carotenoic acid). This means that the crocin underlying saffron's aroma is a digentiobiose ester of the carotenoid crocetin.[17] Crocins themselves are a series of hydrophilic carotenoids that are either monoglycosyl or diglycosyl polyene esters of crocetin.[17] Meanwhile, crocetin is a conjugated polyene dicarboxylic acid that is hydrophobic, and thus oil-soluble. When crocetin is esterified with two water-soluble gentiobioses (which are sugars), a product results that is itself water-soluble. The resultant α-crocin is a carotenoid pigment that may comprise more than 10% of dry saffron's mass. The two esterified gentiobioses make α-crocin ideal for colouring water-based (non-fatty) foods such as rice dishes.[4]
The bitter glucoside picrocrocin is responsible for saffron's flavour. Picrocrocin (chemical formula: C16H26O7; systematic name: 4-(β-D-glucopyranosyloxy)-2,6,6- trimethylcyclohex-1-ene-1-carboxaldehyde) is a union of an aldehyde sub-element known as safranal (systematic name: 2,6,6-trimethylcyclohexa-1,3-dien-1- carboxaldehyde) and a carbohydrate. It has insecticidal and pesticidal properties, and may comprise up to 4% of dry saffron. Significantly, picrocrocin is a truncated version (produced via oxidative cleavage) of the carotenoid zeaxanthin and is the glycoside of the terpene aldehyde safranal. The reddish-coloured[18] zeaxanthin is, incidentally, one of the carotenoids naturally present within the retina of the human eye.
When saffron is dried after its harvest, the heat, combined with enzymatic action, splits picrocrocin to yield D-glucose and a free safranal molecule.[16] Safranal, a volatile oil, gives saffron much of its distinctive aroma.[5][19] Safranal is less bitter than picrocrocin and may comprise up to 70% of dry saffron's volatile fraction in some samples.[18] A second element underlying saffron's aroma is 2-hydroxy-4,4,6-trimethyl-2,5-cyclohexadien-1-one, the scent of which has been described as "saffron, dried hay like".[20] Chemists found this to be the most powerful contributor to saffron's fragrance despite its being present in a lesser quantity than safranal.[20] Dry saffron is highly sensitive to fluctuating pH levels, and rapidly breaks down chemically in the presence of light and oxidizing agents. It must therefore be stored away in air-tight containers in order to minimise contact with atmospheric oxygen. Saffron is somewhat more resistant to heat.
# History
The history of saffron cultivation reaches back more than 3,000 years.[8] The wild precursor of domesticated saffron crocus was Crocus cartwrightianus. Human cultivators bred wild specimens by selecting for unusually long stigmas. Thus, a sterile mutant form of C. cartwrightianus, C. sativus, emerged in late Bronze Age Crete.[21] Experts believe saffron was first documented in a 7th century BC Assyrian botanical reference compiled under Ashurbanipal. Since then, documentation of saffron's use over the span of 4,000 years in the treatment of some 90 illnesses has been uncovered.[22] Saffron has been used as a spice and medicine in the Mediterranean region since then, with usage and cultivation slowly spreading to other parts of Eurasia as well as North Africa and North America. In the last several decades, saffron cultivation has spread to Oceania.
## Mediterranean
Minoans portrayed saffron in their palace frescoes by 1500–1600 BC, showing saffron's use as a therapeutic drug.[23][22] Later, Greek legends told of sea voyages to Cilicia. There, adventurers hoped to procure what they believed was the world's most valuable saffron.[11] Another legend tells of Crocus and Smilax, whereby Crocus is bewitched and transformed into the original saffron crocus.[24] Ancient Mediterranean peoples—including perfumers in Egypt, physicians in Gaza, townspeople in Rhodes,[25] and the Greek hetaerae courtesans—used saffron in their perfumes, ointments,[26] potpourris, mascaras, divine offerings, and medical treatments.[26]
In late Hellenistic Egypt, Cleopatra used saffron in her baths so that lovemaking would be more pleasurable.[27] Egyptian healers used saffron as a treatment for all varieties of gastrointestinal ailments.[28] Saffron was also used as a fabric dye in such Levant cities as Sidon and Tyre.[29] Aulus Cornelius Celsus prescribes saffron in medicines for wounds, cough, colic, and scabies, and in the mithridatium.[30] Such was the Romans' love of saffron that Roman colonists took their saffron with them when they settled in southern Gaul, where it was extensively cultivated until Rome's fall. Competing theories state that saffron only returned to France with 8th century AD Moors or with the Avignon papacy in the 14th century AD.[31]
## Asia
Saffron-based pigments have been found in 50,000 year-old depictions of prehistoric beasts in what is today Iraq.[24][32] Later, the Sumerians used wild-growing saffron in their remedies and magical potions.[33] Saffron was thus an article of long-distance trade before the Minoan palace culture's 2nd millennium BC peak. Saffron was also honored in the Hebrew Song of Solomon.[34] Ancient Persians cultivated Persian saffron (Crocus sativus 'Hausknechtii') in Derbena, Isfahan, and Khorasan by the 10th century BC. At such sites, saffron threads were woven into textiles,[24] ritually offered to divinities, and used in dyes, perfumes, medicines, and body washes.[35] Thus, saffron threads would be scattered across beds and mixed into hot teas as a curative for bouts of melancholy. Non-Persians also feared the Persians' usage of saffron as a drugging agent and aphrodisiac.[26] During his Asian campaigns, Alexander the Great used Persian saffron in his infusions, rice, and baths as a curative for battle wounds. Alexander's troops mimicked the practice and brought saffron-bathing back to Greece.[36]
Theories explaining saffron's arrival in South Asia conflict. Traditional Kashmiri and Chinese accounts date its arrival anywhere between 900–2500 years ago.[37][38] Meanwhile, historians studying ancient Persian records date the arrival to sometime prior to 500 BC,[4] attributing it to either Persian transplantation of saffron corms to stock new gardens and parks[39] or to a Persian invasion and colonization of Kashmir. Phoenicians then marketed Kashmiri saffron as a dye and a treatment for melancholy.[26] From there, saffron use in foods and dyes spread throughout South Asia. For example, Buddhist monks in India adopted saffron-coloured robes after the Buddha Siddhartha Gautama's death.[40]
Some historians believe that saffron first came to China with Mongol invaders by way of Persia.[41] On the other hand, saffron is mentioned in ancient Chinese medical texts, including the forty-volume Shennong Bencaojing (神農本草經—"Shennong's Great Herbal", also known as Pen Ts'ao or Pun Tsao) pharmacopoeia, a tome dating from 200–300 BC. Traditionally attributed to the legendary Yan ("Fire") Emperor (炎帝) Shennong, it documents 252 phytochemical-based medical treatments for various disorders.[42][43][40] Yet around the 3rd century AD, the Chinese were referring to saffron as having a Kashmiri provenance. For example, Wan Zhen, a Chinese medical expert, reported that "[t]he habitat of saffron is in Kashmir, where people grow it principally to offer it to the Buddha." Wan also reflected on how saffron was used in his time: "The [saffron crocus] flower withers after a few days, and then the saffron is obtained. It is valued for its uniform yellow colour. It can be used to aromatise wine."Template:Inote
## Europe
In Europe, saffron cultivation declined steeply following the Roman Empire's fall. Saffron was reintroduced when Moorish civilization spread to Spain, France, and Italy.[44] During the 14th century Black Death, demand for saffron-based medicine skyrocketed, and much saffron had to be imported via Venetian and Genoan ships from southern and Mediterranean lands[45] such as Rhodes. The theft of one such shipment by noblemen sparked the fourteen-week long "Saffron War".[45] The conflict and resulting fear of rampant saffron piracy spurred significant saffron cultivation in Basel, which grew prosperous.[46] Cultivation and trade then spread to Nuremberg, where epidemic levels of saffron adulteration brought on the Safranschou code, under which saffron adulterers were fined, imprisoned, and executed.[47] Soon after, saffron cultivation spread throughout England, especially Norfolk and Suffolk. The Essex town of Saffron Walden, named for its new specialty crop, emerged as England's prime saffron growing and trading center. However, an influx of more exotic spices such as chocolate, coffee, tea, and vanilla from newly contacted Eastern and overseas countries caused European cultivation and usage of saffron to decline.[48][49] Only in southern France, Italy, and Spain, did significant cultivation endure.[50]
Europeans brought saffron to the Americas when immigrant members of the Schwenkfelder Church left Europe with a trunk containing saffron corms; indeed, many Schwenkfelders had widely grown saffron in Europe.[51] By 1730, the Pennsylvania Dutch were cultivating saffron throughout eastern Pennsylvania. Spanish colonies in the Caribbean bought large amounts of this new American saffron, and high demand ensured that saffron's list price on the Philadelphia commodities exchange was set equal to that of gold.[52] The trade with the Caribbean later collapsed in the aftermath of the War of 1812, when many saffron-transporting merchant vessels were destroyed.[53] Yet the Pennsylvania Dutch continued to grow lesser amounts of saffron for local trade and use in their cakes, noodles, and chicken or trout dishes.[54] American saffron cultivation survived into modern times mainly in Lancaster County, Pennsylvania.[51]
# Trade and use
Saffron's aroma is often described by connoisseurs as reminiscent of metallic honey with grassy or hay-like notes, while its taste has been noted also as hay-like and somewhat bitter. Saffron also contributes a luminous yellow-orange colouring to foods. Saffron is widely used in Persian, Arab, Central Asian, European, Indian, Iranian, Moroccan and Cornish cuisines. Confectionaries and liquors also often include saffron. Common saffron substitutes include safflower (Carthamus tinctorius, which is often sold as "Portuguese saffron" or "assafroa") and turmeric (Curcuma longa). Medicinally, saffron has a long history as part of traditional healing; modern medicine has also discovered saffron as having anticarcinogenic (cancer-suppressing),[17] anti-mutagenic (mutation-preventing), immunomodulating, and antioxidant-like properties.[55][17][56] Saffron has also been used as a fabric dye, particularly in China and India, and in perfumery.
Most saffron is grown in a belt of land ranging from the Mediterranean in the west to Kashmir in the east. Annually, around 300 tonnes of saffron are produced worldwide.[6] Iran, Spain, India, Greece, Azerbaijan, Morocco, and Italy (in decreasing order of production) are the major producers of saffron. A pound of dry saffron (0.45 kg) requires 50,000–75,000 flowers, the equivalent of a football field's area of cultivation.[57][58] Some forty hours of frenetic day-and-night labour are needed to pick 150,000 flowers.[59] Upon extraction, stigmas are dried quickly and (preferably) sealed in airtight containers.[60] Saffron prices at wholesale and retail rates range from US$500/pound to US$5,000/pound (US$1100–US$11,000 per kilogram)—equivalent to £2,500/€3,500 per pound or £5,500/€7,500 per kilo. In Western countries, the average retail price is $1,000/£500/€700 per pound (US$2200/£1100/€1550 per kilogram).[2] Between 70,000 and 200,000 threads comprise a pound. Vivid crimson colouring, slight moistness, elasticity, recent harvest date, and lack of broken-off thread debris are all traits of fresh saffron.
# Cultivars
Several saffron cultivars are grown worldwide. Spain's varieties, including the tradenames 'Spanish Superior' and 'Creme', are generally mellower in colour, flavour, and aroma; they are graded by government-imposed standards. Italian varieties are more potent, while the most intense varieties tend to be Macedonian Greek, Iranian, and Indian in origin. Westerners may face significant obstacles in obtaining saffron from India. For example, India has banned the export of high-grade saffron abroad. Aside from these, various "boutique" crops are available from New Zealand, France, Switzerland, England, the United States, and other countries, some organically grown. In the U.S., Pennsylvania Dutch saffron—known for its earthy notes—is marketed in small quantities.[51][61]
Consumers regard certain cultivars as "premium" quality. The "Aquila" saffron (zafferano dell'Aquila)—defined by high safranal and crocin content, shape, unusually pungent aroma, and intense colour—is grown exclusively on eight hectares in the Navelli Valley of Italy's Abruzzo region, near L'Aquila. It was first introduced to Italy by a Dominican monk from Inquisition-era Spain. But in Italy the biggest saffron cultivation, for quality and quantity, is in San Gavino Monreale, Sardinia. There, saffron is grown on 40 hectares (60% of Italian production); it also has very high crocin, picrocrocin, and safranal content. Another is the Kashmiri "Mongra" or "Lacha" saffron (Crocus sativus 'Cashmirianus'), which is among the most difficult for consumers to obtain. Repeated droughts, blights, and crop failures in Kashmir, combined with an Indian export ban, contribute to its high prices. Kashmiri saffron is recognisable by its extremely dark maroon-purple hue, among the world's darkest, which suggests the saffron's strong flavour, aroma, and colourative effect.
# Grades
Saffron types are graded by quality according to laboratory measurements of such characteristics as crocin (colour), picrocrocin (taste), and safranal (fragrance) content. Other metrics include floral waste content (i.e. the saffron spice sample's non-stigma floral content) and measurements of other extraneous matter such as inorganic material ("ash"). A uniform set of international standards in saffron grading was established by the International Organization for Standardization, which is an international federation of national standards bodies. Namely, ISO 3632 deals exclusively with saffron. It establishes four empirical grades of colour intensity: IV (poorest), III, II, and I (finest quality). Saffron samples are then assigned to one of these grades by gauging the spice's crocin content, which is revealed by measurements of crocin-specific spectroscopic absorbance. Absorbance is defined as <math>A_\lambda = -\log(I/I_0)</math>, with <math>A_\lambda</math> as absorbance (Beer-Lambert law). It is a measure of a given substance's transparency (<math>I/I_0</math>, the ratio of light intensity passing through sample to that of the incident light) to a given wavelength of light.
For saffron, absorbance is determined for the crocin-specific photon wavelength of 440 nm in a given dry sample of spice.[62] Higher absorbances at this wavelength imply greater crocin concentration, and thus a greater colourative intensity. These data are measured through spectrophotometry reports at certified testing laboratories worldwide. These colour grades proceed from grades with absorbances lower than 80 (for all category IV saffron) up to 190 or greater (for category I). The world's finest samples (the selected most red-maroon tips of stigmas picked from the finest flowers) receive absorbance scores in excess of 250. Market prices for saffron types follow directly from these ISO scores.[62] However, many growers, traders, and consumers reject such lab test numbers. They prefer a more holistic method of sampling batches of thread for taste, aroma, pliability, and other traits in a fashion similar to that practiced by practised wine tasters.[63]
Despite such attempts at quality control and standardisation, an extensive history of saffron adulteration—particularly among the cheapest grades—continues into modern times. Adulteration was first documented in Europe's Middle Ages, when those found selling adulterated saffron were executed under the Safranschou code.[64] Typical methods include mixing in extraneous substances like beet, pomegranate fibers, red-dyed silk fibers, or the saffron crocus's tasteless and odorless yellow stamens. Other methods included dousing saffron fibers with viscid substances like honey or vegetable oil. However, powdered saffron is more prone to adulteration, with turmeric, paprika, and other powders used as diluting fillers. Adulteration can also consist of selling mislabeled mixes of different saffron grades.[40] Thus, in India, high-grade Kashmiri saffron is often sold mixed with cheaper Iranian imports; these mixes are then marketed as pure Kashmiri saffron, a development that has cost Kashmiri growers much of their income.[65][66]
# Notes
- ↑ Rau 1969, p. 53.
- ↑ Jump up to: 2.0 2.1 2.2 Hill 2004, p. 272.
- ↑ Grigg 1974, p. 287.
- ↑ Jump up to: 4.0 4.1 4.2 McGee 2004, p. 422.
- ↑ Jump up to: 5.0 5.1 McGee 2004, p. 423.
- ↑ Jump up to: 6.0 6.1 6.2 6.3 Katzer 2001.
- ↑ Harper 2001.
- ↑ Jump up to: 8.0 8.1 8.2 8.3 8.4 Deo 2003, p. 1.
- ↑ Willard 2001, p. 3.
- ↑ DPIWE 2005.
- ↑ Jump up to: 11.0 11.1 Willard 2001, pp. 2–3.
- ↑ Jump up to: 12.0 12.1 Deo 2003, p. 2.
- ↑ Jump up to: 13.0 13.1 13.2 Deo 2003, p. 3.
- ↑ Willard 2001, pp. 3–4.
- ↑ Willard 2001, p. 4.
- ↑ Jump up to: 16.0 16.1 Deo 2003, p. 4.
- ↑ Jump up to: 17.0 17.1 17.2 17.3 17.4 Abdullaev 2002, p. 1.
- ↑ Jump up to: 18.0 18.1 Leffingwell 2001, p. 1.
- ↑ Dharmananda 2005.
- ↑ Jump up to: 20.0 20.1 Leffingwell 2001, p. 3.
- ↑ Goyns 1999, p. 1.
- ↑ Jump up to: 22.0 22.1 Honan 2004.
- ↑ Ferrence 2004, p. 1.
- ↑ Jump up to: 24.0 24.1 24.2 Willard 2001, p. 2.
- ↑ Willard 2001, p. 58.
- ↑ Jump up to: 26.0 26.1 26.2 26.3 Willard 2001, p. 41.
- ↑ Willard 2001, p. 55.
- ↑ Willard 2001, pp. 34–35.
- ↑ Willard 2001, p. 59.
- ↑ Celsus, de Medicina, ca. 30 AD, transl. Loeb Classical Library Edition, 1935 [1]
- ↑ Willard 2001, p. 63.
- ↑ Humphries 1998, p. 20.
- ↑ Willard 2001, p. 12.
- ↑ Humphries 1998, p. 19.
- ↑ Willard 2001, pp. 17–18.
- ↑ Willard 2001, pp. 54–55.
- ↑ Lak 1998b.
- ↑ Fotedar 1998–1999, p. 128.
- ↑ Dalby 2003, p. 256.
- ↑ Jump up to: 40.0 40.1 40.2 Tarvand 2005.
- ↑ Fletcher 2005, p. 11.
- ↑ Hayes 2001, p. 6.
- ↑ Shen-Nong Limited 2005.
- ↑ Willard 2001, p. 70.
- ↑ Jump up to: 45.0 45.1 Willard 2001, p. 99.
- ↑ Willard 2001, p. 101.
- ↑ Willard 2001, pp. 103–104.
- ↑ Willard 2001, p. 117.
- ↑ Willard 2001, pp. 132–133.
- ↑ Willard 2001, p. 133.
- ↑ Jump up to: 51.0 51.1 51.2 Willard 2001, p. 143.
- ↑ Willard 2001, p. 138.
- ↑ Willard 2001, pp. 138–139.
- ↑ Willard 2001, pp. 142–146.
- ↑ Assimopoulou 2005, p. 1.
- ↑ Chang, Kuo & Wang 1964, p. 1.
- ↑ Hill 2004, p. 273.
- ↑ Rau 1969, p. 35.
- ↑ Lak 1998.
- ↑ Goyns 1999, p. 8.
- ↑ Willard 2001, p. 201.
- ↑ Jump up to: 62.0 62.1 Tarvand 2005b.
- ↑ Hill 2004, p. 274.
- ↑ Willard 2001, pp. 102–104.
- ↑ Australian Broadcasting Corporation 2003.
- ↑ Hussain 2005.
Template:Col-2 | https://www.wikidoc.org/index.php/Saffron | |
ea7b51d7e8ed3b9716aecaf81375944583766a7d | wikidoc | Safrole | Safrole
Safrole is a colorless or slightly yellow oily liquid. It is typically extracted from the root-bark or the fruit of sassafras plants in the form of sassafras oil, or synthesized from other related methylenedioxy compounds. It is the principal component of brown camphor oil, and is found in small amounts in a wide variety of plants. The Octea cymbarum oil made of the Octea pretiosa,
a plant growing in brazil, and sassafras oil made of the Sassafras albidum, a plant growing in eastern North America, are the main natural sources for safrole. It has a characteristic "candy-shop" aroma.
Safrole was once widely used as a food additive in root beer, sassafras tea, and other common goods. However, the Food and Drug Administration (FDA) barred the use of safrole after it was shown to be mildly carcinogenic. Today, safrole is also banned for use in soap and perfumes by IFRA.
It is a precursor in the synthesis of the insecticide synergist piperonyl butoxide. Safrole is used as the main precursor for the clandestine manufacture of MDMA (ecstasy). The standard synthetic procedure for the production of MDMA from safrole is via isomerization in the presence of a strong base to isosafrole, oxidization to 3,4-methylenedioxy phenyl-2-propanone, finally a reductive amination with either methylamine (to make MDMA) or ethylamine (to make MDEA) or ammonia (to make MDA). A newer synthesis method makes use of the Wacker process (palladium(II) chloride catalyst and 1,4-benzoquinone) to oxidize safrole directly to the 3,4-methylenedioxy phenyl-2-propanone intermediate.
It is nearly impossible to obtain large quantities of safrole and/or sassafras oil without arousing the suspicion of law enforcement, as Safrole is currently a List I chemical. Moreover, safrole is listed as a Table I precursor under the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. | Safrole
Template:Chembox new
Safrole is a colorless or slightly yellow oily liquid. It is typically extracted from the root-bark or the fruit of sassafras plants in the form of sassafras oil, or synthesized from other related methylenedioxy compounds. It is the principal component of brown camphor oil, and is found in small amounts in a wide variety of plants. The Octea cymbarum oil made of the Octea pretiosa,[1]
a plant growing in brazil, and sassafras oil made of the Sassafras albidum,[2] a plant growing in eastern North America, are the main natural sources for safrole. It has a characteristic "candy-shop" aroma.
Safrole was once widely used as a food additive in root beer, sassafras tea, and other common goods. However, the Food and Drug Administration (FDA) barred the use of safrole after it was shown to be mildly carcinogenic. Today, safrole is also banned for use in soap and perfumes by IFRA.
It is a precursor in the synthesis of the insecticide synergist piperonyl butoxide. Safrole is used as the main precursor for the clandestine manufacture of MDMA (ecstasy). The standard synthetic procedure for the production of MDMA from safrole is via isomerization in the presence of a strong base to isosafrole, oxidization to 3,4-methylenedioxy phenyl-2-propanone, finally a reductive amination with either methylamine (to make MDMA) or ethylamine (to make MDEA) or ammonia (to make MDA). A newer synthesis method makes use of the Wacker process (palladium(II) chloride catalyst and 1,4-benzoquinone) to oxidize safrole directly to the 3,4-methylenedioxy phenyl-2-propanone intermediate.
It is nearly impossible to obtain large quantities of safrole and/or sassafras oil without arousing the suspicion of law enforcement, as Safrole is currently a List I chemical. Moreover, safrole is listed as a Table I precursor under the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.[3] | https://www.wikidoc.org/index.php/Safrole | |
d167b99d57bdbc3882f57357c21ffc8a06696c93 | wikidoc | SandBox | SandBox
# Cough
# Overview
# Classification
Cough can be classified based on duration i.e
- Acute cough: This type of cough usually presents with a duration of fewer than 3 weeks.
- Sub Acute cough: Last between 3-8weeks.
- Chronic Cough: Chronic cough usually presents for a duration greater than 8weeks.
Cough can also be classified based on sputum production i.e
- Non-productive cough.
- Productive cough.
# Pathophysiology
The act of cough is a vital one that occurs through the stimulation of the cough reflex which is a complex relex arc. The cough reflex arc is constituted by 3 main components ie
- The Afferent pathway: This made up of sensory nerve fibers in the ciliated epithelium found in the upper airways. The afferent impulses are transmitted into the medulla.
- The efferent pathway: cough impulses that is originated from the cough central travels via the vagus nerve,phrenic nerve, and spinal motor nerves to the diaphragm and abdominal wall muscles.
- Central pathway: This is a central area located within the pons and brainstem. It coordinates the cough reflex arc.
The Afferent sensory nerves:There are 3 manjor classes of afferent sensory nerves,this classification is based on there conduction velocity(A-fiber, > 3 m/s; C-fiber, < 2 m/s),origin ,myelination,neurochemistry etc.
- Rapidly adapting receptors (RARs)
- Slowly adapting stretch receptors (SARs)
- C-fibres.
The series of mechanical activities that take place during coughing is divided into 3 phases.
- The inspiratory phase: Here there in inhalation of an appropriate amount of air needed to produce cough.
- The Compression Phase: The contraction of the muscles of the chest wall, abdominal wall, and the diaphragm against a closed larynx brings about a rapid increase in intrathoracic pressure.
- The Expiratory Phase: At this last phase the glottis is open bringing about a large expiratory airflow and the unique sound associated with coughing.
# Causes
The common causes of cough are:
- Bronchial asthma.
- GERD.
- Postnasal drip.
- Post viral cough.
- Allergic rhinitis.
Less common causes of cough are:
# Cough Differential Diagnosis
- Acute Cough Diffrential Diagnosis.
- Subacute cough Differential diagnosis.
- Chronic cough Differential Diagnosis.
# Overview
Associated symptoms such as fever, vomiting, night sweats, weight loss, sputum production and quantity, smoking history, drug use, etc help the clinician with making a list of plausible differential diagnoses.
# Differentiating cough from other Diseases
Making a differential diagnosis when a patient presents with a cough can be challenging however the clinician should utilize other associated symptoms such as fever, vomiting, night sweats, weight loss, sputum production and quantity, smoking history, drug use and most importantly the duration of the cough to make a list of plausible differential diagnoses.
# Cough epidemiology and demographics
Cough is the most common cause of visits to primary care doctors and pulmonologist, it accounts for about 40% of outpatient visits.
# Risk Factors for cough
The risk factors for cough are closely linked with its various causes, however, certain factors such as smoking, seasonal allergies, and air pollution can increase a patients cough hypersensitivity.
# Natural History, Complications and Prognosis
# Diagnosis
- Cough History and Symptoms: The physician should take a detailed history from the patient with an emphasis on the duration of the cough, sputum production,hemoptysis, chest pain, etc.
- Cough Physical examination: A complete respiratory and cardiac examination should be performed.
- ECG: should be performed when cough due to cardiac pathology is suspected.
- Cough chest x-ray: Should be done for most cases of cough.
- CT|MRI|Echocardiogram|Laboratory findings
# Treatment
- medical therapy: Most patients with cough utilizes cough medication with different pharmacologic constituents to help achieve relief. For patients with a productive cough the utilization of cough medication with mucolytic agents such as Guaifenesin,Bromhexine, helps achieve cough relief by clearing the mucus from the respiratory tract but when treating dry cough the use of antitussive and other cough suppressants such as codeine and dextromethorphan can be utilized. I t is important for the clinician to avoid symptomatic treatment of cough and an underlying cause should always be looked for especially when a cough persists for a long duration or not relieved after trial of various cough medications.
- Surgery|prevention|future or investigational therapies | SandBox
# Cough
Editor-In-Chief: C. Michael Gibson, M.S., M.D.; Associate Editor(s)-in-Chief:Abiodun Akanmode
# Overview
# Classification
Cough can be classified based on duration i.e
- Acute cough: This type of cough usually presents with a duration of fewer than 3 weeks.
- Sub Acute cough: Last between 3-8weeks.
- Chronic Cough: Chronic cough usually presents for a duration greater than 8weeks.
Cough can also be classified based on sputum production i.e
- Non-productive cough.
- Productive cough.
# Pathophysiology
The act of cough is a vital one that occurs through the stimulation of the cough reflex which is a complex relex arc. The cough reflex arc is constituted by 3 main components ie
- The Afferent pathway: This made up of sensory nerve fibers in the ciliated epithelium found in the upper airways. The afferent impulses are transmitted into the medulla.
- The efferent pathway: cough impulses that is originated from the cough central travels via the vagus nerve,phrenic nerve, and spinal motor nerves to the diaphragm and abdominal wall muscles.
- Central pathway: This is a central area located within the pons and brainstem. It coordinates the cough reflex arc.
The Afferent sensory nerves:There are 3 manjor classes of afferent sensory nerves,this classification is based on there conduction velocity(A-fiber, > 3 m/s; C-fiber, < 2 m/s),origin ,myelination,neurochemistry etc.
- Rapidly adapting receptors (RARs)
- Slowly adapting stretch receptors (SARs)
- C-fibres.
The series of mechanical activities that take place during coughing is divided into 3 phases.
- The inspiratory phase: Here there in inhalation of an appropriate amount of air needed to produce cough.
- The Compression Phase: The contraction of the muscles of the chest wall, abdominal wall, and the diaphragm against a closed larynx brings about a rapid increase in intrathoracic pressure.
- The Expiratory Phase: At this last phase the glottis is open bringing about a large expiratory airflow and the unique sound associated with coughing.
# Causes
The common causes of cough are:
- Bronchial asthma.
- GERD.
- Postnasal drip.
- Post viral cough.
- Allergic rhinitis.
Less common causes of cough are:
# Cough Differential Diagnosis
- Acute Cough Diffrential Diagnosis.
- Subacute cough Differential diagnosis.
- Chronic cough Differential Diagnosis.
# Overview
Associated symptoms such as fever, vomiting, night sweats, weight loss, sputum production and quantity, smoking history, drug use, etc help the clinician with making a list of plausible differential diagnoses.
# Differentiating cough from other Diseases
Making a differential diagnosis when a patient presents with a cough can be challenging however the clinician should utilize other associated symptoms such as fever, vomiting, night sweats, weight loss, sputum production and quantity, smoking history, drug use and most importantly the duration of the cough to make a list of plausible differential diagnoses.
# Cough epidemiology and demographics
Cough is the most common cause of visits to primary care doctors and pulmonologist, it accounts for about 40% of outpatient visits.
# Risk Factors for cough
The risk factors for cough are closely linked with its various causes, however, certain factors such as smoking, seasonal allergies, and air pollution can increase a patients cough hypersensitivity.
# Natural History, Complications and Prognosis
# Diagnosis
- Cough History and Symptoms: The physician should take a detailed history from the patient with an emphasis on the duration of the cough, sputum production,hemoptysis, chest pain, etc.
- Cough Physical examination: A complete respiratory and cardiac examination should be performed.
- ECG: should be performed when cough due to cardiac pathology is suspected.
- Cough chest x-ray: Should be done for most cases of cough.
- CT|MRI|Echocardiogram|Laboratory findings
# Treatment
- medical therapy: Most patients with cough utilizes cough medication with different pharmacologic constituents to help achieve relief. For patients with a productive cough the utilization of cough medication with mucolytic agents such as Guaifenesin,Bromhexine, helps achieve cough relief by clearing the mucus from the respiratory tract but when treating dry cough the use of antitussive and other cough suppressants such as codeine and dextromethorphan can be utilized. I t is important for the clinician to avoid symptomatic treatment of cough and an underlying cause should always be looked for especially when a cough persists for a long duration or not relieved after trial of various cough medications.
- Surgery|prevention|future or investigational therapies | https://www.wikidoc.org/index.php/SandBox | |
3df21b7f9fc1591a1d901b0dfc24daaba496adeb | wikidoc | Sandbox | Sandbox
Synonyms and keywords: Gammel's disease.
Erythema gyratum repens is a rare highly specific and characteristic paraneoplastic syndrome that usually affect older people. It is characterized by wood-grain scaly skin eruption with intense pruritus. The cause of erythema gyratum repens is unknown but many theories suggest immunologic etiology or toxicologic products that are released by the associated tumor. The first case of erythema gyratum repens was described by a dermatologist named Gammel in the year 1952. For many years after erythema gyratum repens original description, there was little progress in defining the pathogenesis of erythema gyratum repens. Erythema gyratum repens has no specific classification but we can classify it based on its association with an internal malignancy into para-neoplastic and non-para-neoplastic erythema gyratum repens. The most common malignancies associated with erythema gyratum repens are lung or bronchogenic cancer, esophageal cancer, and breast cancer. Erythema gyratum repens can also be associated with non-neoplastic diseases such as tuberculosis, autoimmune disorders, or CREST syndrome. Erythema gyratum repens is characterized by its pathogonomic figurate, gyrate, or annular erythematous skin eruptions. The intense pruritus can be debilitating and usually urges the patient to go to the emergency department. The microscopic histopathological features of erythema gyratum repens consist of acanthosis, focal parakeratotic, and spongiosis of the epidermis with perivascular mononuclear, lymphocytic, and histiocytic infiltrate in the superficial plexus of the dermis. Erythema gyratum repens is very rare and it mainly affects people in their seventieth decade, the male to female ratio is 2:1. Erythema gyratum repens is diagnosed clinically by its characteristic skin eruption and an urgent thorough paraneoplastic workup should be initiated to look for internal malignancies. Patients with erythema gyratum repens presents with intensely pruritic, gradually progressive, skin lesions that crawl rather than migrate from one body region to the other. It can start in the upper trunk or upper back and extends to involve the extremities sparing the face. The mainstay of the treatment of erythema gyratum repens is finding and treating the underlying malignancy. Symptomatic treatment is not very effective in relieving the pruritus and its associated pain. The management can be surgical removal of the tumor, chemotherapy, or palliative conservative management. The skin eruptions can improve completely after the removal of the underlying tumor, or can recur especially if the tumor recurred or metastasized. Patients can live a few weeks, months or up to five years depending on when and at what stage the malignancy was detected.
The association between cutaneous manifestations and systemic malignancies was first studied in 1925 by Rothman, the Hungarian investigative dermatologist, who wrote a comprehensive review on this subject and since then, cases were added to proof for the relationship between internal neoplasm and some skin lesions.
Erythema gyratum repens was first described by Dr. John A Gammel, the dermatologist, who was trained to link bizarre or recalcitrant dermatoses to internal malignancy, In 1952, in a 55-year-old patient who had been complaining of pruritic scaly skin eruption and diagnosed nine months later with poorly differentiated adenocarcinoma of the breast with metastasis to axillary lymph nodes.
In 1950, Dr. Gammel presented his case of Erythema gyratum repens before the Cleveland Dermatological Society as Erythema gyratum migrans then he changed the term to erythema gyratum repens because the eruption does not "migrate" from one place to another but "crawls" constantly in the areas involved, like "ants on an anthill".
In 1973, 45 year old man was diagnosed with erythema gyratum repens associated with metastatic, undifferentiated adenocarcinoma which was removed following a right- sided craniotomy. The patient was misdiagnosed with erythema perstans and the malignancy was discovered after 8 months of the skin manifestations.
Up to 1992, there were only 49 cases in the literature, 41 of which (84%) were associated with a neoplasm and that is why erythema gyratum repens has been considered as a paraneoplastic syndrome.
Between 1990 and 2010, a literature review was done by collecting data from the medical records of patients form dermatology department in University of Genoa and from databases as pubMed and medline, to conclude that erythema gyratum repens is no longer considered as an obligate paraneoplastic syndrome. More than expected cases of EGR were found with no neoplasm association.
# Pathophysiology
The pathogenesis of erythema gyratum repens is unclear
Many immunologic theories have been implicated in its pathogenesis.
The immunologic mechanism theory is evidenced by the observed immunofluorescence patterns of IgG, C3, and C4 at the basement membrane:
Theory 1: the tumor induces antibodies that cross-react with the basement membrane of skin.
Theory 2: the tumor produces polypeptides that bind skin antigens and render them immunogenic.
Theory 3: deposition of tumor antigen-antibody complexes onto the basement membrane causes reactive dermatitis seen in erythema gyratum repens.
The gross appearance of the unique eruptions are:
Wavy erythematous concentric bands that can be figurate, gyrate, or annular
The bands are arranged in parallel rings and lined by a fine trailing edge of scales, a pattern often described as “wood grained”.
The distinctive wood-grain appearance of the eruption is pathognomonic.
The rash typically involves large areas of the body but tends to spare the face, hands, and feet and it can expand as fast as 1 cm a day.
Bullae can also form from within the areas of erythema.
The microscopic histologic features of erythema gyratum repens are not characteristics but the following are the biopsy specimen findings that are compatible with the diagnosis:
The epidermis has thin atrophic patches with areas of acanthosis, focal parakeratotic horny layers, and spongiosis.
The dermis contains a moderate perivascular mononuclear, lymphocytic, and histiocytic infiltrate in the superficial plexus as well as mild focal spongiosis and parakeratosis.
Eosinophils and melanophages have also been reported in the dermal infiltrate.
Diffuse to moderate edema of the connective tissue can be seen.
# Historical Perspective
The association between cutaneous manifestations and systemic malignancies was first studied in 1925 by Rothman, the Hungarian investigative dermatologist, who wrote a comprehensive review on this subject and since then, cases were added to proof for the relationship between internal neoplasm and some skin lesions.
Erythema gyratum repens was first described by Dr. John A Gammel, the dermatologist, who was trained to link bizarre or recalcitrant dermatoses to internal malignancy, In 1952, in a 55-year-old patient who had been complaining of pruritic scaly skin eruption and diagnosed nine months later with poorly differentiated adenocarcinoma of the breast with metastasis to axillary lymph nodes.
In 1950, Dr. Gammel presented his case of Erythema gyratum repens before the Cleveland Dermatological Society as Erythema gyratum migrans then he changed the term to erythema gyratum repens because the eruption does not "migrate" from one place to another but "crawls" constantly in the areas involved, like "ants on an anthill".
In 1973, 45 year old man was diagnosed with erythema gyratum repens associated with metastatic, undifferentiated adenocarcinoma which was removed following a right- sided craniotomy. The patient was misdiagnosed with erythema perstans and the malignancy was discovered after 8 months of the skin manifestations.
Up to 1992, there were only 49 cases in the literature, 41 of which (84%) were associated with a neoplasm and that is why erythema gyratum repens has been considered as a paraneoplastic syndrome.
Between 1990 and 2010, a literature review was done by collecting data from the medical records of patients form dermatology department in University of Genoa and from databases as pubMed and medline, to conclude that erythema gyratum repens is no longer considered as an obligate paraneoplastic syndrome. More than expected cases of EGR were found with no neoplasm association.
# Classification
- There is no established system for the classification of EGR. However, we can classify EGR as:
Paraneoplastic EGR
Non-paraneoplastic EGR could be:
Idiopathic EGR
EGR-like eruptions (different dermatologic lesions that mimic EGR)
EGR with concomitant skin disease as:
pityriasis rubra pilaris, psoriasis, ichthyosis, CREST, rheumatoid arthritis, tuberculosis, bullous pemphigoid, linear IgA disease, and hyper eosinophilic syndrome
Drug-induced EGR examples are:
Azathioprine with type I autoimmune hepatitis
Interferon given for hepatitis C virus–related chronic hepatitis
- Paraneoplastic EGR
- Non-paraneoplastic EGR could be:
Idiopathic EGR
EGR-like eruptions (different dermatologic lesions that mimic EGR)
EGR with concomitant skin disease as:
pityriasis rubra pilaris, psoriasis, ichthyosis, CREST, rheumatoid arthritis, tuberculosis, bullous pemphigoid, linear IgA disease, and hyper eosinophilic syndrome
Drug-induced EGR examples are:
Azathioprine with type I autoimmune hepatitis
Interferon given for hepatitis C virus–related chronic hepatitis
- Idiopathic EGR
- EGR-like eruptions (different dermatologic lesions that mimic EGR)
- EGR with concomitant skin disease as:
pityriasis rubra pilaris, psoriasis, ichthyosis, CREST, rheumatoid arthritis, tuberculosis, bullous pemphigoid, linear IgA disease, and hyper eosinophilic syndrome
- pityriasis rubra pilaris, psoriasis, ichthyosis, CREST, rheumatoid arthritis, tuberculosis, bullous pemphigoid, linear IgA disease, and hyper eosinophilic syndrome
- Drug-induced EGR examples are:
Azathioprine with type I autoimmune hepatitis
Interferon given for hepatitis C virus–related chronic hepatitis
- Azathioprine with type I autoimmune hepatitis
- Interferon given for hepatitis C virus–related chronic hepatitis
# Pathophysiology
- The cause of EGR has not been identified.
- Many theories suggest that EGR is due to immunologic mechanisms. The immunologic mechanism theory is evidenced by the observed immunofluorescence patterns of IgG, C3, and C4 at the basement membrane:
Theory 1 the tumor induces antibodies that cross-react with the basement membrane of skin
Theory 2 the tumor produces polypeptides that bind skin antigens and render them immunogenic
Theory 3 deposition of tumor antigen-antibody complexes onto the basement membrane causes reactive dermatitis seen in EGR
- Theory 1 the tumor induces antibodies that cross-react with the basement membrane of skin
- Theory 2 the tumor produces polypeptides that bind skin antigens and render them immunogenic
- Theory 3 deposition of tumor antigen-antibody complexes onto the basement membrane causes reactive dermatitis seen in EGR
# Causes
- The cause of erythema gyratum repens has not been identified.
- Different theories suggest that EGR etiology is stemmed from an immunologic reaction.
- There is strong evidence of the association of EGR and systemic neoplasm proofed by the improvement of the skin lesions after the neoplasm treatment. However, that association doesn't mean causation.
# Differentiating Erythema Gyratum Repens from Other Diseases
- EGR has a narrow differential diagnosis. It has to be differentiated from Reactive gyrate erythematous eruptions, such as:
Reactive (figurate or gyrate) erythemas that are associated with malignancy include:
Erythema annulare centrifugum (EAC)
Necrolytic migratory erythema (NME)
Reactive (figurate or gyrate) erythemas that are not associated with malignancy include:
Erythema marginatum rheumaticum
Erythema chronicum migrans
Familial annular erythema
The carrier state of chronic granulomatous disease
Subacute cutaneous lupus erythematosus
Neonatal lupus erythematosus
- Reactive (figurate or gyrate) erythemas that are associated with malignancy include:
Erythema annulare centrifugum (EAC)
Necrolytic migratory erythema (NME)
- Erythema annulare centrifugum (EAC)
- Necrolytic migratory erythema (NME)
- Reactive (figurate or gyrate) erythemas that are not associated with malignancy include:
Erythema marginatum rheumaticum
Erythema chronicum migrans
Familial annular erythema
The carrier state of chronic granulomatous disease
Subacute cutaneous lupus erythematosus
Neonatal lupus erythematosus
- Erythema marginatum rheumaticum
- Erythema chronicum migrans
- Familial annular erythema
- The carrier state of chronic granulomatous disease
- Subacute cutaneous lupus erythematosus
- Neonatal lupus erythematosus
# Epidemiology and Demographics
- EGR is a rare dermatologic disease, usually associated with paraneoplastic neoplasm
Age
- The average age of onset of EGR is in the seventh decade of life (65 years old)
Gender
- The male to female ratio is 2:1
Race
- EGR commonly affects Caucasians
# Risk Factors
- There are no established risk factors for EGR
# Screening
- There are no screening tests for EGR.
- Screening for internal malignancy should be done immediately after EGR is diagnosed.
# Natural History, Complications, and Prognosis
- The majority of patients with EGR presents with severely pruritic erythematous skin lesions that appear several months prior to the malignancy diagnosis
- If the underlying malignancy left untreated, the debilitating pruritus could persist until the patient dies
- Prognosis depends on the type of the underlying tumor and the probability of its treatment. It depends on the time of the EGR onset and the neoplasm discovery. The course and prognosis of EGR can be one of the following:
Complete cure of the skin eruption and pruritus after removal and treatment of the internal neoplasm
Temporary improvement then recurrence of the eruption (specially in cases of metastasis)
No effect of the tumor treatment on the course of EGR
Death can occur few weeks after the discovery of the malignancy, few months, or four years as in Gammel's patient.
- Complete cure of the skin eruption and pruritus after removal and treatment of the internal neoplasm
- Temporary improvement then recurrence of the eruption (specially in cases of metastasis)
- No effect of the tumor treatment on the course of EGR
- Death can occur few weeks after the discovery of the malignancy, few months, or four years as in Gammel's patient.
# Diagnosis
## Diagnostic Study of Choice
- EGR is mainly diagnosed clinically by its characteristic skin lesions.
- It is considered as a cutaneous marker of malignancy with high specificity so physicians shouldn't miss its unique clinical skin presentation.
## History and Symptoms
- The universal symptoms of EGR are:
Skin eruptions
Intense pruritus
- Skin eruptions
- Intense pruritus
- Other symptoms related to the associated internal malignancy are:
Weight loss
Anorexia
Fatigue
Fever
Many patients with EGR and malignancy had a history of tobacco smoking
some patients with EGR and malignancy have a family history of neoplasm
- Weight loss
- Anorexia
- Fatigue
- Fever
- Many patients with EGR and malignancy had a history of tobacco smoking
- some patients with EGR and malignancy have a family history of neoplasm
## Physical Examination
- Patients with EGR can be ill-appearing and lethargic
- Thorough physical exam should be done to look for signs of malignancy as lymph node enlargements, mass, abdominal distension, shortness of breath, pleural effusion,or papilloedema.
- The rash consisting of wavy erythematous concentric bands that can be figurate, gyrate, or annular.
- The bands are arranged in parallel rings and lined by a fine trailing edge of scale, a pattern often described as “wood grained.
- The rash typically involves large areas of the body but tends to spare the face, hands, and feet and it can expand as fast as a cm a day.
- Bullae can also form from within the areas of erythema
## Laboratory Findings
- There are no diagnostic laboratory findings associated with EGR.
- Eosinophilia is observed in 60% of cases
- Evaluation to exclude systemic involvement:
CBC, CMP, urine analysis, LFT, guaiac stool test, serum protein electrophoresis
- CBC, CMP, urine analysis, LFT, guaiac stool test, serum protein electrophoresis
## Imaging Findings
- There are no imaging findings associated with EGR.
- Imaging of the chest and abdomen could show malignancy findings.
## Other Diagnostic Studies
- Direct immunofluorescence in some cases shows patterns of IgG, C3, and C4 at the basement membrane
- The histopathologic features of EGR is non-specific.
- Biopsy specimens show the following:
Acanthosis, mild hyperkeratosis, focal parakeratosis, and spongiosis confined to the epidermis and superficial dermis.
Mononuclear, lymphocytic, and histiocytic perivascular infiltrate in the superficial plexus can also be seen
- Acanthosis, mild hyperkeratosis, focal parakeratosis, and spongiosis confined to the epidermis and superficial dermis.
- Mononuclear, lymphocytic, and histiocytic perivascular infiltrate in the superficial plexus can also be seen
- Thorough paraneoplastic workup includes:
Computed tomography of thorax, abdomen, and pelvis
Positron emission tomography/computed tomography
Upper and lower gastrointestinal endoscopy
Tumor markers
Blood tests including lactate dehydrogenase and QuantiFERON to exclude tuberculosis.
- Computed tomography of thorax, abdomen, and pelvis
- Positron emission tomography/computed tomography
- Upper and lower gastrointestinal endoscopy
- Tumor markers
- Blood tests including lactate dehydrogenase and QuantiFERON to exclude tuberculosis.
# Treatment
Medical Therapy
- There is no treatment for EGR; the mainstay of therapy is supportive care and treating the underlying condition
- Various dermatologic and immunosuppressive therapies have been used to treat EGR.
- Systemic steroids are frequently ineffective.
- Topical steroids, vitamin A, and azathioprine have also failed to relieve skin manifestations.
- Improvement of EGR, and its associated intense pruritus depends on recognition and treatment of the underlying malignancy.
- Chemotherapy can be used to treat the internal malignancy.
## Surgery
- Surgical resection of the internal tumor could be recommended as part of the management of EGR.
Prevention
- There are no primary preventive measures available for . | Sandbox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Gammel's disease.
Erythema gyratum repens is a rare highly specific and characteristic paraneoplastic syndrome that usually affect older people. It is characterized by wood-grain scaly skin eruption with intense pruritus. The cause of erythema gyratum repens is unknown but many theories suggest immunologic etiology or toxicologic products that are released by the associated tumor. The first case of erythema gyratum repens was described by a dermatologist named Gammel in the year 1952. For many years after erythema gyratum repens original description, there was little progress in defining the pathogenesis of erythema gyratum repens. Erythema gyratum repens has no specific classification but we can classify it based on its association with an internal malignancy into para-neoplastic and non-para-neoplastic erythema gyratum repens. The most common malignancies associated with erythema gyratum repens are lung or bronchogenic cancer, esophageal cancer, and breast cancer. Erythema gyratum repens can also be associated with non-neoplastic diseases such as tuberculosis, autoimmune disorders, or CREST syndrome. Erythema gyratum repens is characterized by its pathogonomic figurate, gyrate, or annular erythematous skin eruptions. The intense pruritus can be debilitating and usually urges the patient to go to the emergency department. The microscopic histopathological features of erythema gyratum repens consist of acanthosis, focal parakeratotic, and spongiosis of the epidermis with perivascular mononuclear, lymphocytic, and histiocytic infiltrate in the superficial plexus of the dermis. Erythema gyratum repens is very rare and it mainly affects people in their seventieth decade, the male to female ratio is 2:1. Erythema gyratum repens is diagnosed clinically by its characteristic skin eruption and an urgent thorough paraneoplastic workup should be initiated to look for internal malignancies. Patients with erythema gyratum repens presents with intensely pruritic, gradually progressive, skin lesions that crawl rather than migrate from one body region to the other. It can start in the upper trunk or upper back and extends to involve the extremities sparing the face. The mainstay of the treatment of erythema gyratum repens is finding and treating the underlying malignancy. Symptomatic treatment is not very effective in relieving the pruritus and its associated pain. The management can be surgical removal of the tumor, chemotherapy, or palliative conservative management. The skin eruptions can improve completely after the removal of the underlying tumor, or can recur especially if the tumor recurred or metastasized. Patients can live a few weeks, months or up to five years depending on when and at what stage the malignancy was detected.
The association between cutaneous manifestations and systemic malignancies was first studied in 1925 by Rothman, the Hungarian investigative dermatologist, who wrote a comprehensive review on this subject and since then, cases were added to proof for the relationship between internal neoplasm and some skin lesions.[1][2]
Erythema gyratum repens was first described by Dr. John A Gammel, the dermatologist, who was trained to link bizarre or recalcitrant dermatoses to internal malignancy, In 1952, in a 55-year-old patient who had been complaining of pruritic scaly skin eruption and diagnosed nine months later with poorly differentiated adenocarcinoma of the breast with metastasis to axillary lymph nodes.[3][4]
In 1950, Dr. Gammel presented his case of Erythema gyratum repens before the Cleveland Dermatological Society as Erythema gyratum migrans then he changed the term to erythema gyratum repens because the eruption does not "migrate" from one place to another but "crawls" constantly in the areas involved, like "ants on an anthill".[3]
In 1973, 45 year old man was diagnosed with erythema gyratum repens associated with metastatic, undifferentiated adenocarcinoma which was removed following a right- sided craniotomy. The patient was misdiagnosed with erythema perstans and the malignancy was discovered after 8 months of the skin manifestations.[5]
Up to 1992, there were only 49 cases in the literature, 41 of which (84%) were associated with a neoplasm and that is why erythema gyratum repens has been considered as a paraneoplastic syndrome.[6]
Between 1990 and 2010, a literature review was done by collecting data from the medical records of patients form dermatology department in University of Genoa and from databases as pubMed and medline, to conclude that erythema gyratum repens is no longer considered as an obligate paraneoplastic syndrome. More than expected cases of EGR were found with no neoplasm association.[7]
# Pathophysiology
The pathogenesis of erythema gyratum repens is unclear[12][13]
Many immunologic theories have been implicated in its pathogenesis.
The immunologic mechanism theory is evidenced by the observed immunofluorescence patterns of IgG, C3, and C4 at the basement membrane: [13]
Theory 1: the tumor induces antibodies that cross-react with the basement membrane of skin.
Theory 2: the tumor produces polypeptides that bind skin antigens and render them immunogenic.
Theory 3: deposition of tumor antigen-antibody complexes onto the basement membrane causes reactive dermatitis seen in erythema gyratum repens.
The gross appearance of the unique eruptions are:
Wavy erythematous concentric bands that can be figurate, gyrate, or annular
The bands are arranged in parallel rings and lined by a fine trailing edge of scales, a pattern often described as “wood grained”.
The distinctive wood-grain appearance of the eruption is pathognomonic.
The rash typically involves large areas of the body but tends to spare the face, hands, and feet and it can expand as fast as 1 cm a day.
Bullae can also form from within the areas of erythema.
The microscopic histologic features of erythema gyratum repens are not characteristics but the following are the biopsy specimen findings that are compatible with the diagnosis:[3][5][14]
The epidermis has thin atrophic patches with areas of acanthosis, focal parakeratotic horny layers, and spongiosis.
The dermis contains a moderate perivascular mononuclear, lymphocytic, and histiocytic infiltrate in the superficial plexus as well as mild focal spongiosis and parakeratosis.
Eosinophils and melanophages have also been reported in the dermal infiltrate.
Diffuse to moderate edema of the connective tissue can be seen.
# Historical Perspective
The association between cutaneous manifestations and systemic malignancies was first studied in 1925 by Rothman, the Hungarian investigative dermatologist, who wrote a comprehensive review on this subject and since then, cases were added to proof for the relationship between internal neoplasm and some skin lesions.[1][2]
Erythema gyratum repens was first described by Dr. John A Gammel, the dermatologist, who was trained to link bizarre or recalcitrant dermatoses to internal malignancy, In 1952, in a 55-year-old patient who had been complaining of pruritic scaly skin eruption and diagnosed nine months later with poorly differentiated adenocarcinoma of the breast with metastasis to axillary lymph nodes.[3][4]
In 1950, Dr. Gammel presented his case of Erythema gyratum repens before the Cleveland Dermatological Society as Erythema gyratum migrans then he changed the term to erythema gyratum repens because the eruption does not "migrate" from one place to another but "crawls" constantly in the areas involved, like "ants on an anthill".[3]
In 1973, 45 year old man was diagnosed with erythema gyratum repens associated with metastatic, undifferentiated adenocarcinoma which was removed following a right- sided craniotomy. The patient was misdiagnosed with erythema perstans and the malignancy was discovered after 8 months of the skin manifestations.[5]
Up to 1992, there were only 49 cases in the literature, 41 of which (84%) were associated with a neoplasm and that is why erythema gyratum repens has been considered as a paraneoplastic syndrome.[6]
Between 1990 and 2010, a literature review was done by collecting data from the medical records of patients form dermatology department in University of Genoa and from databases as pubMed and medline, to conclude that erythema gyratum repens is no longer considered as an obligate paraneoplastic syndrome. More than expected cases of EGR were found with no neoplasm association.[7]
# Classification
- There is no established system for the classification of EGR. However, we can classify EGR as:
Paraneoplastic EGR
Non-paraneoplastic EGR could be: [1]
Idiopathic EGR
EGR-like eruptions (different dermatologic lesions that mimic EGR)
EGR with concomitant skin disease as:
pityriasis rubra pilaris, psoriasis, ichthyosis, CREST, rheumatoid arthritis, tuberculosis, bullous pemphigoid, linear IgA disease, and hyper eosinophilic syndrome
Drug-induced EGR examples are:
Azathioprine with type I autoimmune hepatitis
Interferon given for hepatitis C virus–related chronic hepatitis [1]
- Paraneoplastic EGR
- Non-paraneoplastic EGR could be: [1]
Idiopathic EGR
EGR-like eruptions (different dermatologic lesions that mimic EGR)
EGR with concomitant skin disease as:
pityriasis rubra pilaris, psoriasis, ichthyosis, CREST, rheumatoid arthritis, tuberculosis, bullous pemphigoid, linear IgA disease, and hyper eosinophilic syndrome
Drug-induced EGR examples are:
Azathioprine with type I autoimmune hepatitis
Interferon given for hepatitis C virus–related chronic hepatitis [1]
- Idiopathic EGR
- EGR-like eruptions (different dermatologic lesions that mimic EGR)
- EGR with concomitant skin disease as:
pityriasis rubra pilaris, psoriasis, ichthyosis, CREST, rheumatoid arthritis, tuberculosis, bullous pemphigoid, linear IgA disease, and hyper eosinophilic syndrome
- pityriasis rubra pilaris, psoriasis, ichthyosis, CREST, rheumatoid arthritis, tuberculosis, bullous pemphigoid, linear IgA disease, and hyper eosinophilic syndrome
- Drug-induced EGR examples are:
Azathioprine with type I autoimmune hepatitis
Interferon given for hepatitis C virus–related chronic hepatitis [1]
- Azathioprine with type I autoimmune hepatitis
- Interferon given for hepatitis C virus–related chronic hepatitis [1]
# Pathophysiology
- The cause of EGR has not been identified.
- Many theories suggest that EGR is due to immunologic mechanisms. The immunologic mechanism theory is evidenced by the observed immunofluorescence patterns of IgG, C3, and C4 at the basement membrane: [2]
Theory 1 the tumor induces antibodies that cross-react with the basement membrane of skin
Theory 2 the tumor produces polypeptides that bind skin antigens and render them immunogenic
Theory 3 deposition of tumor antigen-antibody complexes onto the basement membrane causes reactive dermatitis seen in EGR
- Theory 1 the tumor induces antibodies that cross-react with the basement membrane of skin
- Theory 2 the tumor produces polypeptides that bind skin antigens and render them immunogenic
- Theory 3 deposition of tumor antigen-antibody complexes onto the basement membrane causes reactive dermatitis seen in EGR
[2]
# Causes
- The cause of erythema gyratum repens has not been identified.
- Different theories suggest that EGR etiology is stemmed from an immunologic reaction.
- There is strong evidence of the association of EGR and systemic neoplasm proofed by the improvement of the skin lesions after the neoplasm treatment. However, that association doesn't mean causation.
# Differentiating Erythema Gyratum Repens from Other Diseases
- EGR has a narrow differential diagnosis. It has to be differentiated from Reactive gyrate erythematous eruptions, such as: [2]
Reactive (figurate or gyrate) erythemas that are associated with malignancy include:
Erythema annulare centrifugum (EAC)
Necrolytic migratory erythema (NME)
Reactive (figurate or gyrate) erythemas that are not associated with malignancy include:
Erythema marginatum rheumaticum [3]
Erythema chronicum migrans
Familial annular erythema
The carrier state of chronic granulomatous disease
Subacute cutaneous lupus erythematosus
Neonatal lupus erythematosus
- Reactive (figurate or gyrate) erythemas that are associated with malignancy include:
Erythema annulare centrifugum (EAC)
Necrolytic migratory erythema (NME)
- Erythema annulare centrifugum (EAC)
- Necrolytic migratory erythema (NME)
- Reactive (figurate or gyrate) erythemas that are not associated with malignancy include:
Erythema marginatum rheumaticum [3]
Erythema chronicum migrans
Familial annular erythema
The carrier state of chronic granulomatous disease
Subacute cutaneous lupus erythematosus
Neonatal lupus erythematosus
- Erythema marginatum rheumaticum [3]
- Erythema chronicum migrans
- Familial annular erythema
- The carrier state of chronic granulomatous disease
- Subacute cutaneous lupus erythematosus
- Neonatal lupus erythematosus
# Epidemiology and Demographics
- EGR is a rare dermatologic disease, usually associated with paraneoplastic neoplasm
Age
- The average age of onset of EGR is in the seventh decade of life (65 years old)
Gender
- The male to female ratio is 2:1
Race
- EGR commonly affects Caucasians
# Risk Factors
- There are no established risk factors for EGR
# Screening
- There are no screening tests for EGR.
- Screening for internal malignancy should be done immediately after EGR is diagnosed.
# Natural History, Complications, and Prognosis
- The majority of patients with EGR presents with severely pruritic erythematous skin lesions that appear several months prior to the malignancy diagnosis [2]
- If the underlying malignancy left untreated, the debilitating pruritus could persist until the patient dies [2]
- Prognosis depends on the type of the underlying tumor and the probability of its treatment. It depends on the time of the EGR onset and the neoplasm discovery. The course and prognosis of EGR can be one of the following:
Complete cure of the skin eruption and pruritus after removal and treatment of the internal neoplasm
Temporary improvement then recurrence of the eruption (specially in cases of metastasis)
No effect of the tumor treatment on the course of EGR
Death can occur few weeks after the discovery of the malignancy, few months, or four years as in Gammel's patient.
- Complete cure of the skin eruption and pruritus after removal and treatment of the internal neoplasm
- Temporary improvement then recurrence of the eruption (specially in cases of metastasis)
- No effect of the tumor treatment on the course of EGR
- Death can occur few weeks after the discovery of the malignancy, few months, or four years as in Gammel's patient.
# Diagnosis
## Diagnostic Study of Choice
- EGR is mainly diagnosed clinically by its characteristic skin lesions.
- It is considered as a cutaneous marker of malignancy with high specificity so physicians shouldn't miss its unique clinical skin presentation.
## History and Symptoms
- The universal symptoms of EGR are:
Skin eruptions
Intense pruritus
- Skin eruptions
- Intense pruritus
- Other symptoms related to the associated internal malignancy are:
Weight loss
Anorexia
Fatigue
Fever
Many patients with EGR and malignancy had a history of tobacco smoking
some patients with EGR and malignancy have a family history of neoplasm
- Weight loss
- Anorexia
- Fatigue
- Fever
- Many patients with EGR and malignancy had a history of tobacco smoking
- some patients with EGR and malignancy have a family history of neoplasm
## Physical Examination
- Patients with EGR can be ill-appearing and lethargic
- Thorough physical exam should be done to look for signs of malignancy as lymph node enlargements, mass, abdominal distension, shortness of breath, pleural effusion,or papilloedema.
- The rash consisting of wavy erythematous concentric bands that can be figurate, gyrate, or annular.
- The bands are arranged in parallel rings and lined by a fine trailing edge of scale, a pattern often described as “wood grained.
- The rash typically involves large areas of the body but tends to spare the face, hands, and feet and it can expand as fast as a cm a day.
- Bullae can also form from within the areas of erythema [2]
## Laboratory Findings
- There are no diagnostic laboratory findings associated with EGR.
- Eosinophilia is observed in 60% of cases [2]
- Evaluation to exclude systemic involvement:
CBC, CMP, urine analysis, LFT, guaiac stool test, serum protein electrophoresis
- CBC, CMP, urine analysis, LFT, guaiac stool test, serum protein electrophoresis
## Imaging Findings
- There are no imaging findings associated with EGR.
- Imaging of the chest and abdomen could show malignancy findings.
## Other Diagnostic Studies
- Direct immunofluorescence in some cases shows patterns of IgG, C3, and C4 at the basement membrane [2]
- The histopathologic features of EGR is non-specific.
- Biopsy specimens show the following:
Acanthosis, mild hyperkeratosis, focal parakeratosis, and spongiosis confined to the epidermis and superficial dermis.
Mononuclear, lymphocytic, and histiocytic perivascular infiltrate in the superficial plexus can also be seen [2]
- Acanthosis, mild hyperkeratosis, focal parakeratosis, and spongiosis confined to the epidermis and superficial dermis.
- Mononuclear, lymphocytic, and histiocytic perivascular infiltrate in the superficial plexus can also be seen [2]
- Thorough paraneoplastic workup includes: [4]
Computed tomography of thorax, abdomen, and pelvis
Positron emission tomography/computed tomography
Upper and lower gastrointestinal endoscopy
Tumor markers
Blood tests including lactate dehydrogenase and QuantiFERON to exclude tuberculosis.
- Computed tomography of thorax, abdomen, and pelvis
- Positron emission tomography/computed tomography
- Upper and lower gastrointestinal endoscopy
- Tumor markers
- Blood tests including lactate dehydrogenase and QuantiFERON to exclude tuberculosis.
# Treatment
Medical Therapy
- There is no treatment for EGR; the mainstay of therapy is supportive care and treating the underlying condition [2]
- Various dermatologic and immunosuppressive therapies have been used to treat EGR.
- Systemic steroids are frequently ineffective.
- Topical steroids, vitamin A, and azathioprine have also failed to relieve skin manifestations.
- Improvement of EGR, and its associated intense pruritus depends on recognition and treatment of the underlying malignancy.
- Chemotherapy can be used to treat the internal malignancy.
## Surgery
- Surgical resection of the internal tumor could be recommended as part of the management of EGR.
Prevention
- There are no primary preventive measures available for [disease name]. | https://www.wikidoc.org/index.php/Sandbox | |
5c1d49969da82e5e6f1d714635a1d62dc3d45663 | wikidoc | Sardine | Sardine
# Overview
Sardines, or pilchards, are common names used to refer to various small, oily fish within the herring family of Clupeidae. The term sardine was first used in English during the early 15th century and may come from the Mediterranean island of Sardinia, around which sardines were once abundant.
The terms sardine and pilchard are not precise, and what is meant depends on the region. The United Kingdom's Sea Fish Industry Authority, for example, classifies sardines as young pilchards.One criterion suggests fish shorter in length than are sardines, and larger ones pilchards.The FAO/WHO Codex standard for canned sardines cites 21 species that may be classed as sardines; FishBase, a comprehensive database of information about fish, calls at least six species "pilchard", over a dozen just "sardine", and many more with the two basic names qualified by various adjectives.
# Genera
Sardines occur in several genera
- Genus Dussumieria
Rainbow sardine (Dussumieria acuta)
Slender rainbow sardine (Dussumieria elopsoides)
- Rainbow sardine (Dussumieria acuta)
- Slender rainbow sardine (Dussumieria elopsoides)
- Genus Escualosa
Slender white sardine (Escualosa elongata)
White sardine (Escualosa thoracata)
- Slender white sardine (Escualosa elongata)
- White sardine (Escualosa thoracata)
- Genus Sardina
European pilchard (true sardine) (Sardina pilchardus)
- European pilchard (true sardine) (Sardina pilchardus)
- Genus Sardinella
Goldstripe sardinella (Sardinella gibbosa)
Indian oil sardine (Sardinella longiceps)
Round sardinella (Sardinella aurita)
- Goldstripe sardinella (Sardinella gibbosa)
- Indian oil sardine (Sardinella longiceps)
- Round sardinella (Sardinella aurita)
- Genus Sardinops
South American pilchard (Sardinops sagax)
- South American pilchard (Sardinops sagax)
# Species
0s (see chart below).]]
† There are four distinct stocks in the genus Sardinops, widely separated by geography. The FAO treats these stocks as separate species, while FishBase treats them as one species, Sardinops sagax.
# Fisheries
Typically, sardines are caught with encircling nets, particularly purse seines. Many modifications of encircling nets are used, including traps or weirs. The latter are stationary enclosures composed of stakes into which schools of sardines are diverted as they swim along the coast. The fish are caught mainly at night, when they approach the surface to feed on plankton. After harvesting, the fish are submerged in brine while they are transported to shore.
Sardines are commercially fished for a variety of uses: for bait; for immediate consumption; for drying, salting, or smoking; and for reduction into fish meal or oil. The chief use of sardines is for human consumption, but fish meal is used as animal feed, while sardine oil has many uses, including the manufacture of paint, varnish and linoleum.
# As food
Sardines are commonly consumed by human beings. Fresh sardines are often grilled, pickled or smoked, or preserved in cans.
Sardines are rich in vitamins and minerals. A small serving of sardines once a day can provide 13 percent of vitamin B2; roughly one-quarter of niacin; and about 150 percent of the recommended daily value of vitamin B12. All B vitamins help to support proper nervous system function and are used for energy metabolism, or converting food into energy.Also, sardines are high in the major minerals such as phosphorus, calcium, potassium, and some trace minerals including iron and selenium. Sardines are also a natural source of marine omega-3 fatty acids, which may reduce the occurrence of cardiovascular disease. Recent studies suggest that regular consumption of omega-3 fatty acids reduces the likelihood of developing Alzheimer's disease. These fatty acids can also lower blood sugar levels. They are also a good source of vitamin D, calcium, vitamin B12, and protein.
Because they are low in the food chain, sardines are very low in contaminants such as mercury, relative to other fish commonly eaten by humans.
# History
Pilchard fishing and processing became a thriving industry in Cornwall (UK) from around 1750 to around 1880, after which it went into decline. As of 2007, however, stocks are improving. Since 1997, sardines from Cornwall have been sold as "Cornish sardines", and since March 2010, under EU law, Cornish sardines have Protected Geographical Status. The industry has featured in numerous works of art, particularly by Stanhope Forbes and other Newlyn School artists.
In the United States, the sardine canning industry peaked in the 1950s. Since then, the industry has been on the decline. The canneries in Monterey Bay, in what was known as Cannery Row, failed in the mid-1950s. The last large sardine cannery in the United States, the Stinson Seafood plant in Prospect Harbor, Maine, closed its doors on 15 April 2010 after 135 years in operation.
The traditional "Toast to Pilchards" refers to the lucrative export of the fish to Catholic Europe:
# Popular culture
The close packing of sardines in the can has led to their metaphorical use of the name in describing any situation where people or objects are crowded together, for instance, in a bus or subway car. This phenomenon is satirised by British poet and comic Spike Milligan in his poem 'Sardine Submarine'. In the poem, a sardine's mother describes the unfamiliar sight of a submarine to its offspring as 'a tinful of people'.
'Sardines' is also the name of a children's game, where one person hides and each successive person who finds the hidden one packs into the same space until there is only one left out, who becomes the next one to hide. | Sardine
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Sardines, or pilchards, are common names used to refer to various small, oily fish within the herring family of Clupeidae. The term sardine was first used in English during the early 15th century and may come from the Mediterranean island of Sardinia, around which sardines were once abundant.
The terms sardine and pilchard are not precise, and what is meant depends on the region. The United Kingdom's Sea Fish Industry Authority, for example, classifies sardines as young pilchards.One criterion suggests fish shorter in length than are sardines, and larger ones pilchards.The FAO/WHO Codex standard for canned sardines cites 21 species that may be classed as sardines;[1] FishBase, a comprehensive database of information about fish, calls at least six species "pilchard", over a dozen just "sardine", and many more with the two basic names qualified by various adjectives.
# Genera
Sardines occur in several genera
- Genus Dussumieria
Rainbow sardine (Dussumieria acuta)
Slender rainbow sardine (Dussumieria elopsoides)
- Rainbow sardine (Dussumieria acuta)
- Slender rainbow sardine (Dussumieria elopsoides)
- Genus Escualosa
Slender white sardine (Escualosa elongata)
White sardine (Escualosa thoracata)
- Slender white sardine (Escualosa elongata)
- White sardine (Escualosa thoracata)
- Genus Sardina
European pilchard (true sardine) (Sardina pilchardus)
- European pilchard (true sardine) (Sardina pilchardus)
- Genus Sardinella
Goldstripe sardinella (Sardinella gibbosa)
Indian oil sardine (Sardinella longiceps)
Round sardinella (Sardinella aurita)
- Goldstripe sardinella (Sardinella gibbosa)
- Indian oil sardine (Sardinella longiceps)
- Round sardinella (Sardinella aurita)
- Genus Sardinops
South American pilchard (Sardinops sagax)
- South American pilchard (Sardinops sagax)
# Species
Template:Common fish
0s (see chart below).]]
† There are four distinct stocks in the genus Sardinops, widely separated by geography. The FAO treats these stocks as separate species, while FishBase treats them as one species, Sardinops sagax.[41]
# Fisheries
Typically, sardines are caught with encircling nets, particularly purse seines. Many modifications of encircling nets are used, including traps or weirs. The latter are stationary enclosures composed of stakes into which schools of sardines are diverted as they swim along the coast. The fish are caught mainly at night, when they approach the surface to feed on plankton. After harvesting, the fish are submerged in brine while they are transported to shore.
Sardines are commercially fished for a variety of uses: for bait; for immediate consumption; for drying, salting, or smoking; and for reduction into fish meal or oil. The chief use of sardines is for human consumption, but fish meal is used as animal feed, while sardine oil has many uses, including the manufacture of paint, varnish and linoleum.
# As food
Sardines are commonly consumed by human beings. Fresh sardines are often grilled, pickled or smoked, or preserved in cans.
Sardines are rich in vitamins and minerals. A small serving of sardines once a day can provide 13 percent of vitamin B2; roughly one-quarter of niacin; and about 150 percent of the recommended daily value of vitamin B12. All B vitamins help to support proper nervous system function and are used for energy metabolism, or converting food into energy.Also, sardines are high in the major minerals such as phosphorus, calcium, potassium, and some trace minerals including iron and selenium. Sardines are also a natural source of marine omega-3 fatty acids, which may reduce the occurrence of cardiovascular disease.[43] Recent studies suggest that regular consumption of omega-3 fatty acids reduces the likelihood of developing Alzheimer's disease.[44] These fatty acids can also lower blood sugar levels.[45] They are also a good source of vitamin D,[46] calcium, vitamin B12,[47][48] and protein.
Because they are low in the food chain, sardines are very low in contaminants such as mercury, relative to other fish commonly eaten by humans.
# History
Pilchard fishing and processing became a thriving industry in Cornwall (UK) from around 1750 to around 1880, after which it went into decline. As of 2007, however, stocks are improving. Since 1997, sardines from Cornwall have been sold as "Cornish sardines", and since March 2010, under EU law, Cornish sardines have Protected Geographical Status. The industry has featured in numerous works of art, particularly by Stanhope Forbes and other Newlyn School artists.
In the United States, the sardine canning industry peaked in the 1950s. Since then, the industry has been on the decline. The canneries in Monterey Bay, in what was known as Cannery Row, failed in the mid-1950s. The last large sardine cannery in the United States, the Stinson Seafood plant in Prospect Harbor, Maine, closed its doors on 15 April 2010 after 135 years in operation.
The traditional "Toast to Pilchards" refers to the lucrative export of the fish to Catholic Europe:
# Popular culture
The close packing of sardines in the can has led to their metaphorical use of the name in describing any situation where people or objects are crowded together, for instance, in a bus or subway car. This phenomenon is satirised by British poet and comic Spike Milligan in his poem 'Sardine Submarine'. In the poem, a sardine's mother describes the unfamiliar sight of a submarine to its offspring as 'a tinful of people'.[50]
'Sardines' is also the name of a children's game, where one person hides and each successive person who finds the hidden one packs into the same space until there is only one left out, who becomes the next one to hide.[51] | https://www.wikidoc.org/index.php/Sardine | |
343b8ef86eea8b7d838bae6dba6596a93ae16db6 | wikidoc | Sativex | Sativex
Sativex is an oromucosal (mouth) spray developed by the UK company GW Pharmaceuticals for multiple sclerosis patients, who can use it to alleviate neuropathic pain and spasticity. Sativex is distinct from all other pharmaceutically produced cannabinoids currently available because it is derived from botanical material, rather than a solely synthetic process. Sativex is a pharmaceutical product standardised in composition, formulation, and dose. Its principal active cannabinoid components are the cannabinoids: tetrahydrocannabinol (THC) and cannabidiol (CBD). The product is formulated as an oromucosal spray which is administered by spraying into the mouth. Each spray of Sativex delivers a fixed dose of 2.7mg THC and 2.5mg CBD.
Approved by Health Canada under a license with conditions (NOC/c) for prescription use in April 2005, Sativex is the world's first pharmaceutical prescription medicine derived from the cannabis plant. The product is approved in Canada as adjunctive treatment for the symptomatic relief of neuropathic pain in multiple sclerosis. In June 2007, Health Canada issuing a Qualifying Notice for the approval of Sativex in the relief of cancer pain, with the final approval of this indication expected by fall 2007. It is available in the UK as an unlicensed medicine which enables UK doctors to prescribe the product to individual patients who they consider may benefit. It is also available in Catalonia, Spain, for 600 patients suffering from multiple sclerosis and a number of other conditions under a compassionate access programme (130 of the patients will be people with multiple sclerosis, a further 130 will be patients with neuropathic pain arising from a range of medical conditions, 40 will be suffering from anorexia and malnutrition caused by AIDS, and the remaining 300 will be cancer patients undergoing chemotherapy and suffering from nausea and vomiting).
In February 2007, GW and Otsuka Pharmaceutical announced an exclusive agreement for Otsuka to develop and market Sativex in the United States. Otsuka is a major global pharmaceutical company, best known for its antipsychotic blockbuster medication, Abilify. Sativex has received permission from the US regulatory authority, the FDA, to enter directly into late stage Phase III trials in the US. The first large scale US trial in the US for cancer patients is expected to start in summer 2007. The 300-patient, double-blind, randomized, placebo-controlled study will evaluate the effect of Sativex in relieving average daily pain, reducing the use of breakthrough opioid medications, improving the quality of sleep and relevant aspects of quality of life among other outcome measures.
In December 2005, GW and the Spanish pharmaceutical company Almirall announced an exclusive agreement for Almirall to market Sativex in Europe (excluding the UK). In the UK and Canada, Bayer HealthCare have been appointed as exclusive distributors.
In clinical trials, Sativex has generally been well tolerated.
Compare dronabinol (marketed as Marinol), a synthetic version of THC. | Sativex
Sativex is an oromucosal (mouth) spray developed by the UK company GW Pharmaceuticals for multiple sclerosis patients, who can use it to alleviate neuropathic pain and spasticity. Sativex is distinct from all other pharmaceutically produced cannabinoids currently available because it is derived from botanical material, rather than a solely synthetic process. Sativex is a pharmaceutical product standardised in composition, formulation, and dose. Its principal active cannabinoid components are the cannabinoids: tetrahydrocannabinol (THC) and cannabidiol (CBD). The product is formulated as an oromucosal spray which is administered by spraying into the mouth. Each spray of Sativex delivers a fixed dose of 2.7mg THC and 2.5mg CBD.
Approved by Health Canada under a license with conditions (NOC/c) for prescription use in April 2005, Sativex is the world's first pharmaceutical prescription medicine derived from the cannabis plant. The product is approved in Canada as adjunctive treatment for the symptomatic relief of neuropathic pain in multiple sclerosis. In June 2007, Health Canada issuing a Qualifying Notice for the approval of Sativex in the relief of cancer pain, with the final approval of this indication expected by fall 2007. It is available in the UK as an unlicensed medicine which enables UK doctors to prescribe the product to individual patients who they consider may benefit. It is also available in Catalonia, Spain, for 600 patients suffering from multiple sclerosis and a number of other conditions under a compassionate access programme (130 of the patients will be people with multiple sclerosis, a further 130 will be patients with neuropathic pain arising from a range of medical conditions, 40 will be suffering from anorexia and malnutrition caused by AIDS, and the remaining 300 will be cancer patients undergoing chemotherapy and suffering from nausea and vomiting).
In February 2007, GW and Otsuka Pharmaceutical announced an exclusive agreement for Otsuka to develop and market Sativex in the United States. Otsuka is a major global pharmaceutical company, best known for its antipsychotic blockbuster medication, Abilify. Sativex has received permission from the US regulatory authority, the FDA, to enter directly into late stage Phase III trials in the US. The first large scale US trial in the US for cancer patients is expected to start in summer 2007. The 300-patient, double-blind, randomized, placebo-controlled study will evaluate the effect of Sativex in relieving average daily pain, reducing the use of breakthrough opioid medications, improving the quality of sleep and relevant aspects of quality of life among other outcome measures.
In December 2005, GW and the Spanish pharmaceutical company Almirall announced an exclusive agreement for Almirall to market Sativex in Europe (excluding the UK). In the UK and Canada, Bayer HealthCare have been appointed as exclusive distributors.
In clinical trials, Sativex has generally been well tolerated.
[1]
[2]
[3]
Compare dronabinol (marketed as Marinol), a synthetic version of THC. | https://www.wikidoc.org/index.php/Sativex | |
edbdf443f0d5775517683a3eabbe5f5e3f669c21 | wikidoc | Serenoa | Serenoa
Serenoa repens, the saw palmetto, is the sole species currently classified in the genus Serenoa. It has been known by a number of synonyms, including Sabal serrulatum, under which name it still often appears in alternative medicine. It is a small palm, normally reaching a height of around 2-4 m. Its trunk is sprawling, and it grows in clumps or dense thickets in sandy coastal lands or as undergrowth in pine woods or hardwood hammocks. Erect stems or trunks are rarely produced but are found in some populations. It is endemic to the southeastern United States, most commonly along the Atlantic and Gulf coastal plains, but also as far inland as southern Arkansas. It is extremely slow growing, and long lived, with some plants, especially in Florida, possibly being as old as 500-700 years old.
Saw palmetto is a fan palm (Arecaceae tribe Corypheae), with the leaves with a bare petiole terminating in a rounded fan of about 20 leaflets. The petiole is armed with fine, sharp teeth or spines that give the species its common name. The leaves are light green inland, and silvery-white in coastal regions. The leaves are 1-2 m in length, the leaflets 50-100 cm long. They are similar to the leaves of the palmettos of genus Sabal. The flowers are yellowish-white, about 5 mm across, produced in dense compound panicles up to 60 cm long. The fruit is a large reddish-black drupe and is an important food source for wildlife. The plant is used as a food plant by the larvae of some Lepidoptera species including Batrachedra decoctor (which feeds exclusively on the plant).
The genus name honors American botanist Sereno Watson.
## Saw palmetto extract
The fruits of the saw palmetto are highly enriched with fatty acids and phytosterols, and extracts of the fruits have been the subject of intensive research for the treatment of urinary tract infections.
The existing literature on S repens for treatment of BPH is limited in terms of the short duration of studies and variability in study design, use of phytotherapeutic preparations, and reports of outcomes. However, the evidence suggests that S repens improves urologic symptoms and flow measures. Compared with finasteride, S repens produces similar improvement in urinary tract symptoms and urinary flow and was associated with fewer adverse treatment events. Further research is needed using standardized preparations of S repens to determine its long-term effectiveness and ability to prevent BPH complications.
# References and external links
- ↑ Template:Cite paper
- ↑ Wilt TJ; et al. (1998). "Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review". JAMA. 280: 1604&ndash, 1609.CS1 maint: Explicit use of et al. (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- Serenoa in Flora of North America
- Serenoa repens
- Serenoa repens from Floridata
de:Sägepalme
hr:Serenoa repens
it:Serenoa repens
nl:Serenoa repens | Serenoa
Serenoa repens, the saw palmetto, is the sole species currently classified in the genus Serenoa. It has been known by a number of synonyms, including Sabal serrulatum, under which name it still often appears in alternative medicine. It is a small palm, normally reaching a height of around 2-4 m. Its trunk is sprawling, and it grows in clumps or dense thickets in sandy coastal lands or as undergrowth in pine woods or hardwood hammocks. Erect stems or trunks are rarely produced but are found in some populations. It is endemic to the southeastern United States, most commonly along the Atlantic and Gulf coastal plains, but also as far inland as southern Arkansas. It is extremely slow growing, and long lived, with some plants, especially in Florida, possibly being as old as 500-700 years old[1].
Saw palmetto is a fan palm (Arecaceae tribe Corypheae), with the leaves with a bare petiole terminating in a rounded fan of about 20 leaflets. The petiole is armed with fine, sharp teeth or spines that give the species its common name. The leaves are light green inland, and silvery-white in coastal regions. The leaves are 1-2 m in length, the leaflets 50-100 cm long. They are similar to the leaves of the palmettos of genus Sabal. The flowers are yellowish-white, about 5 mm across, produced in dense compound panicles up to 60 cm long. The fruit is a large reddish-black drupe and is an important food source for wildlife. The plant is used as a food plant by the larvae of some Lepidoptera species including Batrachedra decoctor (which feeds exclusively on the plant).
The genus name honors American botanist Sereno Watson.
## Saw palmetto extract
The fruits of the saw palmetto are highly enriched with fatty acids and phytosterols, and extracts of the fruits have been the subject of intensive research for the treatment of urinary tract infections.
The existing literature on S repens for treatment of BPH is limited in terms of the short duration of studies and variability in study design, use of phytotherapeutic preparations, and reports of outcomes. However, the evidence suggests that S repens improves urologic symptoms and flow measures. Compared with finasteride, S repens produces similar improvement in urinary tract symptoms and urinary flow and was associated with fewer adverse treatment events. Further research is needed using standardized preparations of S repens to determine its long-term effectiveness and ability to prevent BPH complications. [2]
# References and external links
- ↑ Template:Cite paper
- ↑ Wilt TJ; et al. (1998). "Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review". JAMA. 280: 1604&ndash, 1609.CS1 maint: Explicit use of et al. (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- Serenoa in Flora of North America
- Serenoa repens
- Serenoa repens from Floridata
de:Sägepalme
hr:Serenoa repens
it:Serenoa repens
nl:Serenoa repens
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Saw_Palmetto | |
aae79bcd7bae077e6828781d8520068762e72e34 | wikidoc | Scapula | Scapula
In anatomy, the scapula, or shoulder blade, is the bone that connects the humerus (arm bone) with the clavicle (collar bone).
The scapula forms the posterior part of the shoulder girdle. In humans, it is a flat bone, roughly triangular in shape.
# Features
It has two surfaces, three borders, and three angles.
The anterior (front) side of the scapula shows the fossa subscapularis (subscapular fossa) to which the subscapularis muscle attaches.
The posterior surface of the scapula is divided by a bony projection, the spina scapulae (opposite to the fossa subscapularis) into the supraspinous fossa and the infraspinous fossa. This projection is called the spine of the scapula. It begins flat at the base of the shoulder bone, ascends in distal direction to its peak at about the middle of the scapula, this peak is called tuber scapulae. After this peak the spina scapulae steeply decays in height. For humans and carnivores and bovinae the spina runs into a forward pointing hook called acromion, which continues past the main part of the bone.
Another hook-like projection comes off the lateral angle of the scapula, and is called the coracoid process. The end of this hook is the site of attachment of many muscles, such as the coracobrachialis muscle.
Near the base of the coracoid process, so also on the lateral angle, there is a depression called the glenoid cavity. This forms the socket that the head of the humerus articulates with.
The scapula also articulates with the clavicle, via the acromion process (the acromioclavicular joint).
# Muscles
The following muscles attach to the scapula:
# Surfaces
## Costal
The costal or ventral surface presents a broad concavity, the subscapular fossa.
The medial two-thirds of this fossa are marked by several oblique ridges, which run lateralward and upward. The ridges give attachment to the tendinous insertions, and the surfaces between them to the fleshy fibers, of the Subscapularis. The lateral third of the fossa is smooth and covered by the fibers of this muscle.
The subscapular fossa is separated from the vertebral border by smooth triangular areas at the medial and inferior angles, and in the interval between these by a narrow ridge which is often deficient. These triangular areas and the intervening ridge afford attachment to the Serratus anterior.
At the upper part of the fossa is a transverse depression, where the bone appears to be bent on itself along a line at right angles to and passing through the center of the glenoid cavity, forming a considerable angle, called the subscapular angle; this gives greater strength to the body of the bone by its arched form, while the summit of the arch serves to support the spine and acromion.
## Dorsal
The dorsal surface is arched from above downward, and is subdivided into two unequal parts by the spine; the portion above the spine is called the supraspinatous fossa, and that below it the infraspinous fossa.
- The supraspinous fossa, the smaller of the two, is concave, smooth, and broader at its vertebral than at its humeral end; its medial two-thirds give origin to the Supraspinatus.
- The infraspinous fossa is much larger than the preceding; toward its vertebral margin a shallow concavity is seen at its upper part; its center presents a prominent convexity, while near the axillary border is a deep groove which runs from the upper toward the lower part. The medial two-thirds of the fossa give origin to the Infraspinatus; the lateral third is covered by this muscle.
The dorsal surface is marked near the axillary border by an elevated ridge, which runs from the lower part of the glenoid cavity, downward and backward to the vertebral border, about 2.5 cm above the inferior angle.
The ridge serves for the attachment of a fibrous septum, which separates the Infraspinatus from the Teres major and Teres minor.
The surface between the ridge and the axillary border is narrow in the upper two-thirds of its extent, and is crossed near its center by a groove for the passage of the scapular circumflex vessels; it affords attachment to the Teres minor.
Its lower third presents a broader, somewhat triangular surface, which gives origin to the Teres major, and over which the Latissimus dorsi glides; frequently the latter muscle takes origin by a few fibers from this part.
The broad and narrow portions above alluded to are separated by an oblique line, which runs from the axillary border, downward and backward, to meet the elevated ridge: to it is attached a fibrous septum which separates the Teres muscles from each other.
# The Acromion
The acromion forms the summit of the shoulder, and is a large, somewhat triangular or oblong process, flattened from behind forward, projecting at first lateralward, and then curving forward and upward, so as to overhang the glenoid cavity.
# Borders
There are three borders of the scapula:
- The superior border is the shortest and thinnest; it is concave, and extends from the medial angle to the base of the coracoid process.
- The axillary border (or "lateral border") is the thickest of the three. It begins above at the lower margin of the glenoid cavity, and inclines obliquely downward and backward to the inferior angle.
- The vertebral border (or "medial border") is the longest of the three, and extends from the medial to the inferior angle.
# Angles
There are three angles:
- The medial angle (or "superior angle")
- The inferior angle
- The lateral angle
# Structure
The head, processes, and the thickened parts of the bone, contain cancellous tissue; the rest consists of a thin layer of compact tissue.
The central part of the supraspinatous fossa and the upper part of the infraspinatous fossa, but especially the former, are usually so thin as to be semitransparent; occasionally the bone is found wanting in this situation, and the adjacent muscles are separated only by fibrous tissue.
# Movements
Movements of the scapula are brought about by scapular muscles:
Elevation,
Depression,
Protraction,
Retraction,
Lateral rotation,
(Medial rotation) | Scapula
Template:Infobox Bone
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]
In anatomy, the scapula, or shoulder blade, is the bone that connects the humerus (arm bone) with the clavicle (collar bone).
The scapula forms the posterior part of the shoulder girdle. In humans, it is a flat bone, roughly triangular in shape.
# Features
It has two surfaces, three borders, and three angles.
The anterior (front) side of the scapula shows the fossa subscapularis (subscapular fossa) to which the subscapularis muscle attaches.
The posterior surface of the scapula is divided by a bony projection, the spina scapulae (opposite to the fossa subscapularis) into the supraspinous fossa and the infraspinous fossa. This projection is called the spine of the scapula. It begins flat at the base of the shoulder bone, ascends in distal direction to its peak at about the middle of the scapula, this peak is called tuber scapulae. After this peak the spina scapulae steeply decays in height. For humans and carnivores and bovinae the spina runs into a forward pointing hook called acromion, which continues past the main part of the bone.
Another hook-like projection comes off the lateral angle of the scapula, and is called the coracoid process. The end of this hook is the site of attachment of many muscles, such as the coracobrachialis muscle.
Near the base of the coracoid process, so also on the lateral angle, there is a depression called the glenoid cavity. This forms the socket that the head of the humerus articulates with.
The scapula also articulates with the clavicle, via the acromion process (the acromioclavicular joint).
# Muscles
The following muscles attach to the scapula:
# Surfaces
## Costal
The costal or ventral surface [Fig. 1] presents a broad concavity, the subscapular fossa.
The medial two-thirds of this fossa are marked by several oblique ridges, which run lateralward and upward. The ridges give attachment to the tendinous insertions, and the surfaces between them to the fleshy fibers, of the Subscapularis. The lateral third of the fossa is smooth and covered by the fibers of this muscle.
The subscapular fossa is separated from the vertebral border by smooth triangular areas at the medial and inferior angles, and in the interval between these by a narrow ridge which is often deficient. These triangular areas and the intervening ridge afford attachment to the Serratus anterior.
At the upper part of the fossa is a transverse depression, where the bone appears to be bent on itself along a line at right angles to and passing through the center of the glenoid cavity, forming a considerable angle, called the subscapular angle; this gives greater strength to the body of the bone by its arched form, while the summit of the arch serves to support the spine and acromion.
## Dorsal
The dorsal surface [Fig. 2] is arched from above downward, and is subdivided into two unequal parts by the spine; the portion above the spine is called the supraspinatous fossa, and that below it the infraspinous fossa.
- The supraspinous fossa, the smaller of the two, is concave, smooth, and broader at its vertebral than at its humeral end; its medial two-thirds give origin to the Supraspinatus.
- The infraspinous fossa is much larger than the preceding; toward its vertebral margin a shallow concavity is seen at its upper part; its center presents a prominent convexity, while near the axillary border is a deep groove which runs from the upper toward the lower part. The medial two-thirds of the fossa give origin to the Infraspinatus; the lateral third is covered by this muscle.
The dorsal surface is marked near the axillary border by an elevated ridge, which runs from the lower part of the glenoid cavity, downward and backward to the vertebral border, about 2.5 cm above the inferior angle.
The ridge serves for the attachment of a fibrous septum, which separates the Infraspinatus from the Teres major and Teres minor.
The surface between the ridge and the axillary border is narrow in the upper two-thirds of its extent, and is crossed near its center by a groove for the passage of the scapular circumflex vessels; it affords attachment to the Teres minor.
Its lower third presents a broader, somewhat triangular surface, which gives origin to the Teres major, and over which the Latissimus dorsi glides; frequently the latter muscle takes origin by a few fibers from this part.
The broad and narrow portions above alluded to are separated by an oblique line, which runs from the axillary border, downward and backward, to meet the elevated ridge: to it is attached a fibrous septum which separates the Teres muscles from each other.
# The Acromion
The acromion forms the summit of the shoulder, and is a large, somewhat triangular or oblong process, flattened from behind forward, projecting at first lateralward, and then curving forward and upward, so as to overhang the glenoid cavity.
# Borders
There are three borders of the scapula:
- The superior border is the shortest and thinnest; it is concave, and extends from the medial angle to the base of the coracoid process.
- The axillary border (or "lateral border") is the thickest of the three. It begins above at the lower margin of the glenoid cavity, and inclines obliquely downward and backward to the inferior angle.
- The vertebral border (or "medial border") is the longest of the three, and extends from the medial to the inferior angle.
# Angles
There are three angles:
- The medial angle (or "superior angle")
- The inferior angle
- The lateral angle
# Structure
The head, processes, and the thickened parts of the bone, contain cancellous tissue; the rest consists of a thin layer of compact tissue.
The central part of the supraspinatous fossa and the upper part of the infraspinatous fossa, but especially the former, are usually so thin as to be semitransparent; occasionally the bone is found wanting in this situation, and the adjacent muscles are separated only by fibrous tissue.
# Movements
Movements of the scapula are brought about by scapular muscles:
Elevation,
Depression,
Protraction,
Retraction,
Lateral rotation,
(Medial rotation)
# External links
- Template:SUNYAnatomyLabs - "Joints of the Upper Extremity: Scapula
# Sources
Template:Gray's
Additions have been made from "Nickel; Schummer; Seiferle; Lehrbuch der Anatomie der Haussäugetiere. | https://www.wikidoc.org/index.php/Scapula | |
0fd01ca8bdb1d07afba55638a8dead241cda568d | wikidoc | Science | Science
Science (from the Latin scientia, meaning "knowledge") is the effort to understand, or to understand better, how the physical world works, with observable evidence as the basis of that understanding. It is done through observation of phenomena, and/or through experimentation that tries to simulate events under controlled conditions.
# Etymology
The word science is derived from the Latin word error: {{lang}}: text has italic markup (help) for knowledge, the nominal form of the verb error: {{lang}}: text has italic markup (help), "to know". The Proto-Indo-European (PIE) root that yields scire is *skei-, meaning to "cut, separate, or discern". Other words from the same root include Sanskrit Template:Transl, "he cuts off", Greek Template:Transl, "I split" (hence English schism, schizophrenia), Latin error: {{lang}}: text has italic markup (help), "I split" (hence English rescind). From the Middle Ages to the Enlightenment, science or scientia meant any systematic recorded knowledge. Science therefore had the same sort of very broad meaning that philosophy had at that time. In other languages, including French, Spanish, Portuguese, and Italian, the word corresponding to science also carries this meaning.
# History of science
Well into the eighteenth century, science and natural philosophy were not quite synonymous, but only became so later with the direct use of what would become known formally as the scientific method, which was earlier developed during the Middle Ages and early modern period in Europe and the Middle East (see History of scientific method). Prior to the 18th century, however, the preferred term for the study of nature was natural philosophy, while English speakers most typically referred to the study of the human mind as moral philosophy. By contrast, the word "science" in English was still used in the 17th century to refer to the Aristotelian concept of knowledge which was secure enough to be used as a sure prescription for exactly how to do something. In this differing sense of the two words, the philosopher John Locke in An Essay Concerning Human Understanding wrote that "natural philosophy is not capable of being made a science".
By the early 1800s, natural philosophy had begun to separate from philosophy, though it often retained a very broad meaning. In many cases, science continued to stand for reliable knowledge about any topic, in the same way it is still used in the broad sense (see the introduction to this article) in modern terms such as library science, political science, and computer science. In the more narrow sense of science, as natural philosophy became linked to an expanding set of well-defined laws (beginning with Galileo's laws, Kepler's laws, and Newton's laws for motion), it became more popular to refer to natural philosophy as natural science. Over the course of the nineteenth century, moreover, there was an increased tendency to associate science with study of the natural world (that is, the non-human world). This move sometimes left the study of human thought and society (what would come to be called social science) in a linguistic limbo by the end of the century and into the next.
Through the 19th century, many English speakers were increasingly differentiating science (meaning a combination of what we now term natural and biological sciences) from all other forms of knowledge in a variety of ways. The now-familiar expression “scientific method,” which refers to the prescriptive part of how to make discoveries in natural philosophy, was almost unused during the early part of the 19th century, but became widespread after the 1870s, though there was rarely totally agreement about just what it entailed. The word "scientist," meant to refer to a systematically-working natural philosopher, (as opposed to an intuitive or empirically-minded one) was coined in 1833 by William Whewell. Discussion of scientists as a special group of people who did science, even if their attributes were up for debate, grew in the last half of the 19th century. Whatever people actually meant by these terms at first, they ultimately depicted science, in the narrow sense of the habitual use of the scientific method and the knowledge derived from it, as something deeply distinguished from all other realms of human endeavor.
By the twentieth century, the modern notion of science as a special brand of information about the world, practiced by a distinct group and pursued through a unique method, was essentially in place. It was used to give legitimacy to a variety of fields through such titles as "scientific" medicine, engineering, advertising, or motherhood. Over the 1900s, links between science and technology also grew increasingly strong. By the end of the century, it is arguable that technology had even begun to eclipse science as a term of public attention and praise. Scholarly studies of science have begun to refer to "technoscience" rather than science of technology separately. Meanwhile, such fields as biotechnology and nanotechnology are capturing the headlines. One author has suggested that, in the coming century, "science" may fall out of use, to be replaced by technoscience or even by some more exotic label such as "techknowledgy."
# Scientific method
The scientific method seeks to explain the events of nature in a reproducible way, and to use these reproductions to make useful predictions. It is done through observation of natural phenomena, and/or through experimentation that tries to simulate natural events under controlled conditions. It provides an objective process to find solutions to problems in a number of scientific and technological fields.
Based on observations of a phenomenon, a scientist may generate a model. This is an attempt to describe or depict the phenomenon in terms of a logical physical or mathematical representation. As empirical evidence is gathered, a scientist can suggest a hypothesis to explain the phenomenon. This description can be used to make predictions that are testable by experiment or observation using the scientific method. When a hypothesis proves unsatisfactory, it is either modified or discarded.
While performing experiments, Scientists may have a preference for one outcome over another, and it is important that this tendency does not bias their interpretation. A strict following of the scientific method attempts to minimize the influence of a scientist's bias on the outcome of an experiment. This can be achieved by correct experimental design, and a thorough peer review of the experimental results as well as conclusions of a study. Once the experiment results are announced or published, an important cross-check can be the need to validate the results by an independent party.
Once a hypothesis has survived testing, it may become adopted into the framework of a scientific theory. This is a logically reasoned, self-consistent model or framework for describing the behavior of certain natural phenomena. A theory typically describes the behavior of much broader sets of phenomena than a hypothesis—commonly, a large number of hypotheses can be logically bound together by a single theory. These broader theories may be formulated using principles such as parsimony (e.g., "Occam's Razor"). They are then repeatedly tested by analyzing how the collected evidence (facts) compares to the theory. When a theory survives a sufficiently large number of empirical observations, it then becomes a scientific generalization that can be taken as fully verified. These assume the status of a physical law or law of nature.
Despite the existence of well-tested theories, science cannot claim absolute knowledge of nature or the behavior of the subject or of the field of study due to epistemological problems that are unavoidable and preclude the discovery or establishment of absolute truth. Unlike a mathematical proof, a scientific theory is empirical, and is always open to falsification, if new evidence is presented. Even the most basic and fundamental theories may turn out to be imperfect if new observations are inconsistent with them. Critical to this process is making every relevant aspect of research publicly available, which allows ongoing review and repeating of experiments and observations by multiple researchers operating independently of one another. Only by fulfilling these expectations can it be determined how reliable the experimental results are for potential use by others.
Isaac Newton's Newtonian law of gravitation is a famous example of an established law that was later found not to be universal—it does not hold in experiments involving motion at speeds close to the speed of light or in close proximity of strong gravitational fields. Outside these conditions, Newton's Laws remain an excellent model of motion and gravity. Since general relativity accounts for all the same phenomena that Newton's Laws do and more, general relativity is now regarded as a more comprehensive theory.
## Mathematics
Mathematics is essential to many sciences. One important function of mathematics in science is the role it plays in the expression of scientific models. Observing and collecting measurements, as well as hypothesizing and predicting, often require extensive use of mathematics and mathematical models. Calculus may be the branch of mathematics most often used in science, but virtually every branch of mathematics has applications in science, including "pure" areas such as number theory and topology. Mathematics is fundamental to the understanding of the natural sciences and the social sciences, many of which also rely heavily on statistics.
Statistical methods, comprised of mathematical techniques for summarizing and exploring data, allow scientists to assess the level of reliability and the range of variation in experimental results. Statistical thinking also plays a fundamental role in many areas of science.
Computational science applies computing power to simulate real-world situations, enabling a better understanding of scientific problems than formal mathematics alone can achieve. According to the Society for Industrial and Applied Mathematics, computation is now as important as theory and experiment in advancing scientific knowledge.
Whether mathematics itself is properly classified as science has been a matter of some debate. Some thinkers see mathematicians as scientists, regarding physical experiments as inessential or mathematical proofs as equivalent to experiments. Others do not see mathematics as a science, since it does not require experimental test of its theories and hypotheses. In practice, mathematical theorems and formulas are obtained by logical derivations which presume axiomatic systems, rather than a combination of empirical observation and method of reasoning that has come to be known as scientific method. In general, mathematics is classified as formal science, while natural and social sciences are classified as empirical sciences.
# Philosophy of science
The philosophy of science seeks to understand the nature and justification of scientific knowledge. It has proven difficult to provide a definitive account of the scientific method that can decisively serve to distinguish science from non-science. Thus there are legitimate arguments about exactly where the borders are, leading to the problem of demarcation. There is nonetheless a set of core precepts that have broad consensus among published philosophers of science and within the scientific community at large.
Science is reasoned-based analysis of sensation upon our awareness. As such, the scientific method cannot deduce anything about the realm of reality that is beyond what is observable by existing or theoretical means. When a manifestation of our reality previously considered supernatural is understood in the terms of causes and consequences, it acquires a scientific explanation.
Some of the findings of science can be very counter-intuitive. Atomic theory, for example, implies that a granite boulder which appears a heavy, hard, solid, grey object is actually a combination of subatomic particles with none of these properties, moving very rapidly in space where the mass is concentrated in a very small fraction of the total volume. Many of humanity's preconceived notions about the workings of the universe have been challenged by new scientific discoveries. Quantum mechanics, particularly, examines phenomena that seem to defy our most basic postulates about causality and fundamental understanding of the world around us. Science is the branch of knowledge dealing with people and the understanding we have of our environment and how it works.
There are different schools of thought in the philosophy of scientific method. Methodological naturalism maintains that scientific investigation must adhere to empirical study and independent verification as a process for properly developing and evaluating natural explanations for observable phenomena. Methodological naturalism, therefore, rejects supernatural explanations, arguments from authority and biased observational studies. Critical rationalism instead holds that unbiased observation is not possible and a demarcation between natural and supernatural explanations is arbitrary; it instead proposes falsifiability as the landmark of empirical theories and falsification as the universal empirical method. Critical rationalism argues for the ability of science to increase the scope of testable knowledge, but at the same time against its authority, by emphasizing its inherent fallibility. It proposes that science should be content with the rational elimination of errors in its theories, not in seeking for their verification (such as claiming certain or probable proof or disproof; both the proposal and falsification of a theory are only of methodological, conjectural, and tentative character in critical rationalism). Instrumentalism rejects the concept of truth and emphasizes merely the utility of theories as instruments for explaining and predicting phenomena.
# Critiques
Karl Popper denied the existence of evidence and of scientific method. Popper holds that there is only one universal method, the negative method of trial and error. It covers not only all products of the human mind, including science, mathematics, philosophy, art and so on, but also the evolution of life.
## Philosophical focus
Historian Jacques Barzun termed science "a faith as fanatical as any in history" and warned against the use of scientific thought to suppress considerations of meaning as integral to human existence. Many recent thinkers, such as Carolyn Merchant, Theodor Adorno and E. F. Schumacher considered that the 17th century scientific revolution shifted science from a focus on understanding nature, or wisdom, to a focus on manipulating nature, i.e. power, and that science's emphasis on manipulating nature leads it inevitably to manipulate people, as well. Science's focus on quantitative measures has led to critiques that it is unable to recognize important qualitative aspects of the world.
The implications of the ideological denial of ethics for the practice of science itself in terms of fraud, plagiarism, and data falsification, has been criticized by several academics. In "Science and Ethics", the philosopher Bernard Rollin examines the ideology that denies the relevance of ethics to science, and argues in favor of making education in ethics part and parcel of scientific training.
## The media and the scientific debate
The mass media face a number of pressures that can prevent them from accurately depicting competing scientific claims in terms of their credibility within the scientific community as a whole. Determining how much weight to give different sides in a scientific debate requires considerable expertise on the issue at hand. Few journalists have real scientific knowledge, and even beat reporters who know a great deal about certain scientific issues may know little about other ones they are suddenly asked to cover.
## Epistemological inadequacies
Psychologist Carl Jung believed that though science attempted to understand all of nature, the experimental method used would pose artificial, conditional questions that evoke only partial answers. Robert Anton Wilson criticized science for using instruments to ask questions that produce answers only meaningful in terms of the instrument, and that there was no such thing as a completely objective vantage point from which to view the results of science.
# Scientific community
The scientific community consists of the total body of scientists, its relationships and interactions. It is normally divided into "sub-communities" each working on a particular field within science.
## Fields
Fields of science are commonly classified along two major lines: natural sciences, which study natural phenomena (including biological life), and social sciences, which study human behavior and societies. These groupings are empirical sciences, which means the knowledge must be based on observable phenomena and capable of being experimented for its validity by other researchers working under the same conditions. There are also related disciplines that are grouped into interdisciplinary and applied sciences, such as engineering and health science. Within these categories are specialized scientific fields that can include elements of other scientific disciplines but often possess their own terminology and body of expertise.
Mathematics, which is sometimes classified within a third group of science called formal science, has both similarities and differences with the natural and social sciences. It is similar to empirical sciences in that it involves an objective, careful and systematic study of an area of knowledge; it is different because of its method of verifying its knowledge, using a priori rather than empirical methods. Formal science, which also includes statistics and logic, is vital to the empirical sciences. Major advances in formal science have often led to major advances in the physical and biological sciences. The formal sciences are essential in the formation of hypotheses, theories, and laws, both in discovering and describing how things work (natural sciences) and how people think and act (social sciences).
The status of social sciences as an empirical science has been a matter of debate since the 20th century (see Positivism dispute). Discussion and debate abound in this topic with some fields like the social and behavioural sciences accused by critics of being unscientific. In fact, many groups of people from academicians like Nobel Prize physicist Percy W. Bridgman, or Dick Richardson, Ph.D.—Professor of Integrative Biology at the University of Texas at Austin, to politicians like U.S. Senator Kay Bailey Hutchison and other co-sponsors, oppose giving their support or agreeing with the use of the label "science" in some fields of study and knowledge they consider non-scientific, ambiguous, or scientifically irrelevant compared with other fields.
## Institutions
Learned societies for the communication and promotion of scientific thought and experimentation have existed since the Renaissance period. The oldest surviving institution is the error: {{lang}}: text has italic markup (help) in Italy. National Academy of Sciences are distinguished institutions that exist in a number of countries, beginning with the British Royal Society in 1660 and the French error: {{lang}}: text has italic markup (help) in 1666.
International scientific organizations, such as the International Council for Science, have since been formed to promote cooperation between the scientific communities of different nations. More recently, influential government agencies have been created to support scientific research, including the National Science Foundation in the U.S.
Other prominent organizations include the academies of science of many nations, CSIRO in Australia, Centre national de la recherche scientifique in France, Max Planck Society and Deutsche Forschungsgemeinschaft in Germany, and in Spain, CSIC.
## Literature
An enormous range of scientific literature is published. Scientific journals communicate and document the results of research carried out in universities and various other research institutions, serving as an archival record of science. The first scientific journals, Journal des Sçavans followed by the Philosophical Transactions, began publication in 1665. Since that time the total number of active periodicals has steadily increased. As of 1981, one estimate for the number of scientific and technical journals in publication was 11,500.
Most scientific journals cover a single scientific field and publish the research within that field; the research is normally expressed in the form of a scientific paper. Science has become so pervasive in modern societies that it is generally considered necessary to communicate the achievements, news, and ambitions of scientists to a wider populace.
Science magazines such as New Scientist and Scientific American cater to the needs of a much wider readership and provide a non-technical summary of popular areas of research, including notable discoveries and advances in certain fields of research. Science books engage the interest of many more people. Tangentially, the science fiction genre, primarily fantastic in nature, engages the public imagination and transmits the ideas, if not the methods, of science.
Recent efforts to intensify or develop links between science and non-scientific disciplines such as Literature or, more specifically, Poetry, include the Creative Writing Science resource developed through the Royal Literary Fund. | Science
Science (from the Latin scientia, meaning "knowledge") is the effort to understand, or to understand better, how the physical world works, with observable evidence as the basis of that understanding. It is done through observation of phenomena, and/or through experimentation that tries to simulate events under controlled conditions.
# Etymology
The word science is derived from the Latin word [scientia] error: {{lang}}: text has italic markup (help) for knowledge, the nominal form of the verb [scire] error: {{lang}}: text has italic markup (help), "to know". The Proto-Indo-European (PIE) root that yields scire is *skei-, meaning to "cut, separate, or discern". Other words from the same root include Sanskrit Template:Transl, "he cuts off", Greek Template:Transl, "I split" (hence English schism, schizophrenia), Latin [scindo] error: {{lang}}: text has italic markup (help), "I split" (hence English rescind).[1] From the Middle Ages to the Enlightenment, science or scientia meant any systematic recorded knowledge.[2] Science therefore had the same sort of very broad meaning that philosophy had at that time. In other languages, including French, Spanish, Portuguese, and Italian, the word corresponding to science also carries this meaning.
# History of science
Well into the eighteenth century, science and natural philosophy were not quite synonymous, but only became so later with the direct use of what would become known formally as the scientific method, which was earlier developed during the Middle Ages and early modern period in Europe and the Middle East (see History of scientific method). Prior to the 18th century, however, the preferred term for the study of nature was natural philosophy, while English speakers most typically referred to the study of the human mind as moral philosophy. By contrast, the word "science" in English was still used in the 17th century to refer to the Aristotelian concept of knowledge which was secure enough to be used as a sure prescription for exactly how to do something. In this differing sense of the two words, the philosopher John Locke in An Essay Concerning Human Understanding wrote that "natural philosophy [the study of nature] is not capable of being made a science".[3]
By the early 1800s, natural philosophy had begun to separate from philosophy, though it often retained a very broad meaning. In many cases, science continued to stand for reliable knowledge about any topic, in the same way it is still used in the broad sense (see the introduction to this article) in modern terms such as library science, political science, and computer science. In the more narrow sense of science, as natural philosophy became linked to an expanding set of well-defined laws (beginning with Galileo's laws, Kepler's laws, and Newton's laws for motion), it became more popular to refer to natural philosophy as natural science. Over the course of the nineteenth century, moreover, there was an increased tendency to associate science with study of the natural world (that is, the non-human world). This move sometimes left the study of human thought and society (what would come to be called social science) in a linguistic limbo by the end of the century and into the next.[4]
Through the 19th century, many English speakers were increasingly differentiating science (meaning a combination of what we now term natural and biological sciences) from all other forms of knowledge in a variety of ways. The now-familiar expression “scientific method,” which refers to the prescriptive part of how to make discoveries in natural philosophy, was almost unused during the early part of the 19th century, but became widespread after the 1870s, though there was rarely totally agreement about just what it entailed.[4] The word "scientist," meant to refer to a systematically-working natural philosopher, (as opposed to an intuitive or empirically-minded one) was coined in 1833 by William Whewell.[5] Discussion of scientists as a special group of people who did science, even if their attributes were up for debate, grew in the last half of the 19th century.[4] Whatever people actually meant by these terms at first, they ultimately depicted science, in the narrow sense of the habitual use of the scientific method and the knowledge derived from it, as something deeply distinguished from all other realms of human endeavor.
By the twentieth century, the modern notion of science as a special brand of information about the world, practiced by a distinct group and pursued through a unique method, was essentially in place. It was used to give legitimacy to a variety of fields through such titles as "scientific" medicine, engineering, advertising, or motherhood.[4] Over the 1900s, links between science and technology also grew increasingly strong. By the end of the century, it is arguable that technology had even begun to eclipse science as a term of public attention and praise. Scholarly studies of science have begun to refer to "technoscience" rather than science of technology separately. Meanwhile, such fields as biotechnology and nanotechnology are capturing the headlines. One author has suggested that, in the coming century, "science" may fall out of use, to be replaced by technoscience or even by some more exotic label such as "techknowledgy."[4]
# Scientific method
The scientific method seeks to explain the events of nature in a reproducible way, and to use these reproductions to make useful predictions. It is done through observation of natural phenomena, and/or through experimentation that tries to simulate natural events under controlled conditions. It provides an objective process to find solutions to problems in a number of scientific and technological fields.[6]
Based on observations of a phenomenon, a scientist may generate a model. This is an attempt to describe or depict the phenomenon in terms of a logical physical or mathematical representation. As empirical evidence is gathered, a scientist can suggest a hypothesis to explain the phenomenon. This description can be used to make predictions that are testable by experiment or observation using the scientific method. When a hypothesis proves unsatisfactory, it is either modified or discarded.
While performing experiments, Scientists may have a preference for one outcome over another, and it is important that this tendency does not bias their interpretation.[7][8] A strict following of the scientific method attempts to minimize the influence of a scientist's bias on the outcome of an experiment. This can be achieved by correct experimental design, and a thorough peer review of the experimental results as well as conclusions of a study.[9][10] Once the experiment results are announced or published, an important cross-check can be the need to validate the results by an independent party.[11]
Once a hypothesis has survived testing, it may become adopted into the framework of a scientific theory. This is a logically reasoned, self-consistent model or framework for describing the behavior of certain natural phenomena. A theory typically describes the behavior of much broader sets of phenomena than a hypothesis—commonly, a large number of hypotheses can be logically bound together by a single theory. These broader theories may be formulated using principles such as parsimony (e.g., "Occam's Razor"). They are then repeatedly tested by analyzing how the collected evidence (facts) compares to the theory. When a theory survives a sufficiently large number of empirical observations, it then becomes a scientific generalization that can be taken as fully verified. These assume the status of a physical law or law of nature.
Despite the existence of well-tested theories, science cannot claim absolute knowledge of nature or the behavior of the subject or of the field of study due to epistemological problems that are unavoidable and preclude the discovery or establishment of absolute truth. Unlike a mathematical proof, a scientific theory is empirical, and is always open to falsification, if new evidence is presented. Even the most basic and fundamental theories may turn out to be imperfect if new observations are inconsistent with them. Critical to this process is making every relevant aspect of research publicly available, which allows ongoing review and repeating of experiments and observations by multiple researchers operating independently of one another. Only by fulfilling these expectations can it be determined how reliable the experimental results are for potential use by others.
Isaac Newton's Newtonian law of gravitation is a famous example of an established law that was later found not to be universal—it does not hold in experiments involving motion at speeds close to the speed of light or in close proximity of strong gravitational fields. Outside these conditions, Newton's Laws remain an excellent model of motion and gravity. Since general relativity accounts for all the same phenomena that Newton's Laws do and more, general relativity is now regarded as a more comprehensive theory.[12]
## Mathematics
Mathematics is essential to many sciences. One important function of mathematics in science is the role it plays in the expression of scientific models. Observing and collecting measurements, as well as hypothesizing and predicting, often require extensive use of mathematics and mathematical models. Calculus may be the branch of mathematics most often used in science, but virtually every branch of mathematics has applications in science, including "pure" areas such as number theory and topology. Mathematics is fundamental to the understanding of the natural sciences and the social sciences, many of which also rely heavily on statistics.
Statistical methods, comprised of mathematical techniques for summarizing and exploring data, allow scientists to assess the level of reliability and the range of variation in experimental results. Statistical thinking also plays a fundamental role in many areas of science.
Computational science applies computing power to simulate real-world situations, enabling a better understanding of scientific problems than formal mathematics alone can achieve. According to the Society for Industrial and Applied Mathematics, computation is now as important as theory and experiment in advancing scientific knowledge.[13]
Whether mathematics itself is properly classified as science has been a matter of some debate. Some thinkers see mathematicians as scientists, regarding physical experiments as inessential or mathematical proofs as equivalent to experiments. Others do not see mathematics as a science, since it does not require experimental test of its theories and hypotheses. In practice, mathematical theorems and formulas are obtained by logical derivations which presume axiomatic systems, rather than a combination of empirical observation and method of reasoning that has come to be known as scientific method. In general, mathematics is classified as formal science, while natural and social sciences are classified as empirical sciences.
# Philosophy of science
The philosophy of science seeks to understand the nature and justification of scientific knowledge. It has proven difficult to provide a definitive account of the scientific method that can decisively serve to distinguish science from non-science. Thus there are legitimate arguments about exactly where the borders are, leading to the problem of demarcation. There is nonetheless a set of core precepts that have broad consensus among published philosophers of science and within the scientific community at large.
Science is reasoned-based analysis of sensation upon our awareness. As such, the scientific method cannot deduce anything about the realm of reality that is beyond what is observable by existing or theoretical means.[14] When a manifestation of our reality previously considered supernatural is understood in the terms of causes and consequences, it acquires a scientific explanation.[15]
Some of the findings of science can be very counter-intuitive. Atomic theory, for example, implies that a granite boulder which appears a heavy, hard, solid, grey object is actually a combination of subatomic particles with none of these properties, moving very rapidly in space where the mass is concentrated in a very small fraction of the total volume. Many of humanity's preconceived notions about the workings of the universe have been challenged by new scientific discoveries. Quantum mechanics, particularly, examines phenomena that seem to defy our most basic postulates about causality and fundamental understanding of the world around us. Science is the branch of knowledge dealing with people and the understanding we have of our environment and how it works.
There are different schools of thought in the philosophy of scientific method. Methodological naturalism maintains that scientific investigation must adhere to empirical study and independent verification as a process for properly developing and evaluating natural explanations for observable phenomena. Methodological naturalism, therefore, rejects supernatural explanations, arguments from authority and biased observational studies. Critical rationalism instead holds that unbiased observation is not possible and a demarcation between natural and supernatural explanations is arbitrary; it instead proposes falsifiability as the landmark of empirical theories and falsification as the universal empirical method. Critical rationalism argues for the ability of science to increase the scope of testable knowledge, but at the same time against its authority, by emphasizing its inherent fallibility. It proposes that science should be content with the rational elimination of errors in its theories, not in seeking for their verification (such as claiming certain or probable proof or disproof; both the proposal and falsification of a theory are only of methodological, conjectural, and tentative character in critical rationalism). Instrumentalism rejects the concept of truth and emphasizes merely the utility of theories as instruments for explaining and predicting phenomena.
# Critiques
Karl Popper denied the existence of evidence[16] and of scientific method.[17] Popper holds that there is only one universal method, the negative method of trial and error. It covers not only all products of the human mind, including science, mathematics, philosophy, art and so on, but also the evolution of life.[18]
## Philosophical focus
Historian Jacques Barzun termed science "a faith as fanatical as any in history" and warned against the use of scientific thought to suppress considerations of meaning as integral to human existence.[19] Many recent thinkers, such as Carolyn Merchant, Theodor Adorno and E. F. Schumacher considered that the 17th century scientific revolution shifted science from a focus on understanding nature, or wisdom, to a focus on manipulating nature, i.e. power, and that science's emphasis on manipulating nature leads it inevitably to manipulate people, as well.[20] Science's focus on quantitative measures has led to critiques that it is unable to recognize important qualitative aspects of the world.[20]
The implications of the ideological denial of ethics for the practice of science itself in terms of fraud, plagiarism, and data falsification, has been criticized by several academics. In "Science and Ethics", the philosopher Bernard Rollin examines the ideology that denies the relevance of ethics to science, and argues in favor of making education in ethics part and parcel of scientific training.[21]
## The media and the scientific debate
The mass media face a number of pressures that can prevent them from accurately depicting competing scientific claims in terms of their credibility within the scientific community as a whole. Determining how much weight to give different sides in a scientific debate requires considerable expertise on the issue at hand.[22] Few journalists have real scientific knowledge, and even beat reporters who know a great deal about certain scientific issues may know little about other ones they are suddenly asked to cover.[23][24]
## Epistemological inadequacies
Psychologist Carl Jung believed that though science attempted to understand all of nature, the experimental method used would pose artificial, conditional questions that evoke only partial answers.[25] Robert Anton Wilson criticized science for using instruments to ask questions that produce answers only meaningful in terms of the instrument, and that there was no such thing as a completely objective vantage point from which to view the results of science.[26]
# Scientific community
The scientific community consists of the total body of scientists, its relationships and interactions. It is normally divided into "sub-communities" each working on a particular field within science.
## Fields
Fields of science are commonly classified along two major lines: natural sciences, which study natural phenomena (including biological life), and social sciences, which study human behavior and societies. These groupings are empirical sciences, which means the knowledge must be based on observable phenomena and capable of being experimented for its validity by other researchers working under the same conditions.[27] There are also related disciplines that are grouped into interdisciplinary and applied sciences, such as engineering and health science. Within these categories are specialized scientific fields that can include elements of other scientific disciplines but often possess their own terminology and body of expertise.[28]
Mathematics, which is sometimes classified within a third group of science called formal science, has both similarities and differences with the natural and social sciences.[27] It is similar to empirical sciences in that it involves an objective, careful and systematic study of an area of knowledge; it is different because of its method of verifying its knowledge, using a priori rather than empirical methods.[27] Formal science, which also includes statistics and logic, is vital to the empirical sciences. Major advances in formal science have often led to major advances in the physical and biological sciences. The formal sciences are essential in the formation of hypotheses, theories, and laws,[27] both in discovering and describing how things work (natural sciences) and how people think and act (social sciences).
The status of social sciences as an empirical science has been a matter of debate since the 20th century (see Positivism dispute).[29] Discussion and debate abound in this topic with some fields like the social and behavioural sciences accused by critics of being unscientific. In fact, many groups of people from academicians like Nobel Prize physicist Percy W. Bridgman,[30] or Dick Richardson, Ph.D.—Professor of Integrative Biology at the University of Texas at Austin,[31] to politicians like U.S. Senator Kay Bailey Hutchison and other co-sponsors,[32] oppose giving their support or agreeing with the use of the label "science" in some fields of study and knowledge they consider non-scientific, ambiguous, or scientifically irrelevant compared with other fields.
## Institutions
Learned societies for the communication and promotion of scientific thought and experimentation have existed since the Renaissance period.[33] The oldest surviving institution is the [Accademia dei Lincei] error: {{lang}}: text has italic markup (help) in Italy.[34] National Academy of Sciences are distinguished institutions that exist in a number of countries, beginning with the British Royal Society in 1660[35] and the French [Académie des Sciences] error: {{lang}}: text has italic markup (help) in 1666.[36]
International scientific organizations, such as the International Council for Science, have since been formed to promote cooperation between the scientific communities of different nations. More recently, influential government agencies have been created to support scientific research, including the National Science Foundation in the U.S.
Other prominent organizations include the academies of science of many nations, CSIRO in Australia, Centre national de la recherche scientifique in France, Max Planck Society and Deutsche Forschungsgemeinschaft in Germany, and in Spain, CSIC.
## Literature
An enormous range of scientific literature is published.[37] Scientific journals communicate and document the results of research carried out in universities and various other research institutions, serving as an archival record of science. The first scientific journals, Journal des Sçavans followed by the Philosophical Transactions, began publication in 1665. Since that time the total number of active periodicals has steadily increased. As of 1981, one estimate for the number of scientific and technical journals in publication was 11,500.[38]
Most scientific journals cover a single scientific field and publish the research within that field; the research is normally expressed in the form of a scientific paper. Science has become so pervasive in modern societies that it is generally considered necessary to communicate the achievements, news, and ambitions of scientists to a wider populace.
Science magazines such as New Scientist and Scientific American cater to the needs of a much wider readership and provide a non-technical summary of popular areas of research, including notable discoveries and advances in certain fields of research. Science books engage the interest of many more people. Tangentially, the science fiction genre, primarily fantastic in nature, engages the public imagination and transmits the ideas, if not the methods, of science.
Recent efforts to intensify or develop links between science and non-scientific disciplines such as Literature or, more specifically, Poetry, include the Creative Writing <-> Science resource developed through the Royal Literary Fund.[39] | https://www.wikidoc.org/index.php/Science | |
49d60b322ed10eb73f546ea9015b3fa48be90875 | wikidoc | Scotoma | Scotoma
# Overview
A scotoma (Greek: darkness; plural: "scotomas" or "scotomata") is an area or island of loss or impairment of visual acuity surrounded by a field of normal or relatively well-preserved vision.
Every normal mammalian eye has a scotoma in its field of vision, usually termed its blind spot. The presence of this normal scotoma does not intrude into consciousness because it is very small, but it can be demonstrated to oneself by the simplest of clinical methods (such as the one in the blind spot article).
# Presentation
Symptom-producing or pathological scotomata may be due to a wide range of disease processes, affecting either the retina (in particular its most sensitive portion, the macula) or the optic nerve itself. A pathological scotoma may involve any part of the visual field and may be of any shape or size. A scotoma may include and enlarge the normal blind spot. Even a small scotoma that happens to affect central or macular vision will produce a severe visual handicap, whereas a large scotoma in the more peripheral part of a visual field may go unnoticed by the bearer due to the normal reduced visual resolution in the peripheral visual field.
# Causes
Common causes of scotomata include demyelinating disease such as multiple sclerosis (retrobulbar neuritis), toxic substances such as methyl alcohol, ethambutol and quinine, nutritional deficiencies, and vascular blockages either in the retina or in the optic nerve. Scintillating scotoma is a common visual aura in migraine. Less common, but important because sometimes reversible or curable by surgery, are scotomata due to tumors such as those arising from the pituitary gland, which may compress the optic nerve or interfere with its blood supply.
Rarely, scotomata are bilateral. One important variety of bilateral scotoma may occur when a pituitary tumour begins to compress the optic chiasm (as distinct from a single optic nerve) and produces a bi-temporal hemicentral scotomatous hemianopia. This type of visual field defect tends to be very eloquent symptom-wise but often evades early objective diagnosis, as it is more difficult to detect by cursory clinical examination than the classical or text-book bi-temporal peripheral hemianopia and may even elude sophisticated electronic modes of visual field assessment.
In a pregant woman, scotomata can present as a symptom of severe preeclampsia, a form of pregnancy-induced hypertension. | Scotoma
# Overview
A scotoma (Greek: darkness; plural: "scotomas" or "scotomata") is an area or island of loss or impairment of visual acuity surrounded by a field of normal or relatively well-preserved vision.
Every normal mammalian eye has a scotoma in its field of vision, usually termed its blind spot. The presence of this normal scotoma does not intrude into consciousness because it is very small, but it can be demonstrated to oneself by the simplest of clinical methods (such as the one in the blind spot article).
# Presentation
Symptom-producing or pathological scotomata may be due to a wide range of disease processes, affecting either the retina (in particular its most sensitive portion, the macula) or the optic nerve itself. A pathological scotoma may involve any part of the visual field and may be of any shape or size. A scotoma may include and enlarge the normal blind spot. Even a small scotoma that happens to affect central or macular vision will produce a severe visual handicap, whereas a large scotoma in the more peripheral part of a visual field may go unnoticed by the bearer due to the normal reduced visual resolution in the peripheral visual field.
# Causes
Common causes of scotomata include demyelinating disease such as multiple sclerosis (retrobulbar neuritis), toxic substances such as methyl alcohol, ethambutol and quinine, nutritional deficiencies, and vascular blockages either in the retina or in the optic nerve. Scintillating scotoma is a common visual aura in migraine.[1] Less common, but important because sometimes reversible or curable by surgery, are scotomata due to tumors such as those arising from the pituitary gland, which may compress the optic nerve or interfere with its blood supply.
Rarely, scotomata are bilateral. One important variety of bilateral scotoma may occur when a pituitary tumour begins to compress the optic chiasm (as distinct from a single optic nerve) and produces a bi-temporal hemicentral scotomatous hemianopia. This type of visual field defect tends to be very eloquent symptom-wise but often evades early objective diagnosis, as it is more difficult to detect by cursory clinical examination than the classical or text-book bi-temporal peripheral hemianopia and may even elude sophisticated electronic modes of visual field assessment.
In a pregant woman, scotomata can present as a symptom of severe preeclampsia, a form of pregnancy-induced hypertension. | https://www.wikidoc.org/index.php/Scotoma | |
9a62d7354576b08268a57680fa9667399f039c7f | wikidoc | Scrapie | Scrapie
Scrapie is a fatal, degenerative disease that affects the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies (TSEs), which are related to bovine spongiform encephalopathy (BSE or "mad cow disease") and chronic wasting disease of deer. Like other spongiform encephalopathies, scrapie is believed to be caused by a prion. Scrapie has been known since the 18th century (1732) and does not appear to be transmissible to humans.
The name scrapie is derived from one of the symptoms of the condition, wherein affected animals will compulsively scrape off their fleece against rocks, trees or fences. The disease apparently causes an itching sensation in the animals. Other symptoms include excessive lip-smacking, strange gaits, and convulsive collapse.
Scrapie is infectious and transmissible among similar animals, and so one of the most common ways to contain scrapie (since it is incurable) is to quarantine and destroy those affected. However, scrapie tends to persist in flocks and can also arise apparently spontaneously in flocks that have not previously had cases of the disease. The mechanism of transmission between animals and other aspects of the biology of the disease are only poorly understood and these are active areas of research. Recent studies suggest that prions may be spread through urine and persist in the environment for decades.
In the United Kingdom, the government has put in place a National Scrapie Plan, which encourages breeding from sheep that are genetically more resistant to scrapie. It is intended that this will eventually reduce the incidence of the disease in the UK sheep population. Scrapie occurs in Europe and North America, but to date Australia and New Zealand (both major sheep-producing countries) are scrapie-free.
A test is now available which is performed by sampling a small amount of lymphatic tissue from the third eyelid.
Out of fear of BSE, many European countries banned some traditional sheep or goat products made without removing the spinal cord such as smalahove and smokie. | Scrapie
Scrapie is a fatal, degenerative disease that affects the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies (TSEs), which are related to bovine spongiform encephalopathy (BSE or "mad cow disease") and chronic wasting disease of deer. Like other spongiform encephalopathies, scrapie is believed to be caused by a prion. Scrapie has been known since the 18th century (1732) and does not appear to be transmissible to humans.
The name scrapie is derived from one of the symptoms of the condition, wherein affected animals will compulsively scrape off their fleece against rocks, trees or fences. The disease apparently causes an itching sensation in the animals. Other symptoms include excessive lip-smacking, strange gaits, and convulsive collapse.
Scrapie is infectious and transmissible among similar animals, and so one of the most common ways to contain scrapie (since it is incurable) is to quarantine and destroy those affected. However, scrapie tends to persist in flocks and can also arise apparently spontaneously in flocks that have not previously had cases of the disease. The mechanism of transmission between animals and other aspects of the biology of the disease are only poorly understood and these are active areas of research. Recent studies suggest that prions may be spread through urine and persist in the environment for decades.
In the United Kingdom, the government has put in place a National Scrapie Plan, which encourages breeding from sheep that are genetically more resistant to scrapie. It is intended that this will eventually reduce the incidence of the disease in the UK sheep population. Scrapie occurs in Europe and North America, but to date Australia and New Zealand (both major sheep-producing countries) are scrapie-free.
A test is now available which is performed by sampling a small amount of lymphatic tissue from the third eyelid.
Out of fear of BSE, many European countries banned some traditional sheep or goat products made without removing the spinal cord such as smalahove and smokie.
# External links
- Article about scrapie and the aforementioned diagnostic test
- UK government scrapie information
- UK government National Scrapie Plan
- Scrapie research at the Institute for Animal Health (UK)
- Sheep genetics research at the Institute for Animal Health (includes photo of a sheep with scrapie)
- Scrapie in the United States
- US Department of Agriculture video of infected sheep demonstrating Hopping Gait
Template:Prion diseases
bg:Скрапия
cs:Scrapie
de:Scrapie
eo:Ŝaftremo
gl:Mal das ovellas tolas
ia:Scrapie
is:Riða
it:Scrapie
nl:Scrapie
fi:Scrapie
sv:Scrapie
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Scrapie | |
ab48aaeb162da599845f65be092e95f82f7bd5bf | wikidoc | Scrotum | Scrotum
# Overview
In some male mammals, the scrotum is a protuberance of skin and muscle containing the testicles. It is an extension of the abdomen, and is located between the penis and anus. In humans, and some other mammals, the base of the scrotum becomes covered with pubic hair at puberty. In common speech, the scrotum is often improperly referred to as the testicles, which actually refer to organs encased inside the scrotum. The scrotum is homologous to the labia majora in females. In slang, the scrotum is often referred to as the "nut sack."
# Function
The function of the scrotum appears to be to keep the testes at a temperature slightly lower than that of the rest of the body. For the human, a temperature around 34.4 degrees Celsius (94 degrees Fahrenheit) seems to be ideal; 36.7 degrees Celsius (98 degree Fahrenheit) may be damaging to sperm count. The temperature is controlled by moving the testicles closer to the abdomen when it is cold, and away when hot. This is done by the contracting and relaxing of the cremaster muscle in the abdomen and the dartos fascia (muscular tissue under the skin) in the scrotum. However, this may not be the main function. The volume of sperm produced by the testes is small, (0.1-0.2ml). It has been suggested that if testes were situated within the abdominal cavity that they would be subjected to the regular changes in abdominal pressure that is exerted by the abdominal muscles. This squeezing and relaxing would result in the more rapid emptying of the testes and epididymes of sperm before the spermatazoa were matured sufficiently for fertilisation. Some mammals do keep their testes within the abdomen and there may be mechanisms to prevent this inadvertent emptying e.g. elephants, sea mammals.
In most biological males, the cremaster muscle itself cannot be controlled voluntarily. Contraction of the abdominal muscles, and changes in intraabdominal pressure, often can lift and lower the testicles within the scrotum. Contraction of the muscle fibers of the dartos tunic (or fascia) is completely involuntary and results in the appearance of increased wrinkling and thickening of the scrotal skin. The testicles are not directly attached to the skin of the scrotum, so this dartos contraction results in their sliding toward the abdomen.
Although the ideal temperature for sperm growth varies between species, it usually appears, in warm-blooded species, to be a bit cooler than internal body temperature, necessitating the scrotum. Since this leaves the testicles vulnerable in many species, there is some debate on the evolutionary advantage of such a system. One theory is that the impregnation of females who are ill is less likely when sperm is highly sensitive to elevated body temperatures.
An alternative explanation is to protect the testes from jolts and compressions associated with an active lifestyle. Animals that have 'stately' movements - such as elephants, whales and marsupial moles - have internal testes and no scrotum.'s
# Health issues
A common problem of the scrotum is the development of masses. Common scrotal masses include
- Sebaceous cyst, also called an epidermal cyst
- hydrocele
- hematocele
- spermatocele
- varicocele
Other conditions include:
- contact dermatitis: may cause redness, swelling, and itching of the entire scrotum. Can result from soaps, solvents, detergents, and natural irritants such as poison ivy.
- inguinal hernia
- yeast infection
- swelling resulting from conditions external to the scrotum, including:
heart failure
kidney or liver disease
- heart failure
- kidney or liver disease
# Additional images
- Structure of the male genitalia.
- Vertical section of bladder, penis, and urethra.
- The superficial branches of the internal pudendal artery.
- A human scrotum, containing the testicles
A human scrotum, containing the testicles | Scrotum
Template:Infobox Anatomy
# Overview
In some male mammals, the scrotum is a protuberance of skin and muscle containing the testicles. It is an extension of the abdomen, and is located between the penis and anus. In humans, and some other mammals, the base of the scrotum becomes covered with pubic hair at puberty. In common speech, the scrotum is often improperly referred to as the testicles, which actually refer to organs encased inside the scrotum. The scrotum is homologous to the labia majora in females. In slang, the scrotum is often referred to as the "nut sack."
# Function
The function of the scrotum appears to be to keep the testes at a temperature slightly lower than that of the rest of the body. For the human, a temperature around 34.4 degrees Celsius (94 degrees Fahrenheit) seems to be ideal; 36.7 degrees Celsius (98 degree Fahrenheit) may be damaging to sperm count. The temperature is controlled by moving the testicles closer to the abdomen when it is cold, and away when hot. This is done by the contracting and relaxing of the cremaster muscle in the abdomen and the dartos fascia (muscular tissue under the skin) in the scrotum. However, this may not be the main function. The volume of sperm produced by the testes is small, (0.1-0.2ml). It has been suggested that if testes were situated within the abdominal cavity that they would be subjected to the regular changes in abdominal pressure that is exerted by the abdominal muscles. This squeezing and relaxing would result in the more rapid emptying of the testes and epididymes of sperm before the spermatazoa were matured sufficiently for fertilisation. Some mammals do keep their testes within the abdomen and there may be mechanisms to prevent this inadvertent emptying e.g. elephants, sea mammals.
In most biological males, the cremaster muscle itself cannot be controlled voluntarily. Contraction of the abdominal muscles, and changes in intraabdominal pressure, often can lift and lower the testicles within the scrotum. Contraction of the muscle fibers of the dartos tunic (or fascia) is completely involuntary and results in the appearance of increased wrinkling and thickening of the scrotal skin. The testicles are not directly attached to the skin of the scrotum, so this dartos contraction results in their sliding toward the abdomen.
Although the ideal temperature for sperm growth varies between species, it usually appears, in warm-blooded species, to be a bit cooler than internal body temperature, necessitating the scrotum. Since this leaves the testicles vulnerable in many species, there is some debate on the evolutionary advantage of such a system. One theory is that the impregnation of females who are ill is less likely when sperm is highly sensitive to elevated body temperatures.
An alternative explanation is to protect the testes from jolts and compressions associated with an active lifestyle. Animals that have 'stately' movements - such as elephants, whales and marsupial moles - have internal testes and no scrotum.[1]'s
# Health issues
A common problem of the scrotum is the development of masses. Common scrotal masses include
- Sebaceous cyst, also called an epidermal cyst
- hydrocele
- hematocele
- spermatocele
- varicocele
Other conditions include:
- contact dermatitis: may cause redness, swelling, and itching of the entire scrotum. Can result from soaps, solvents, detergents, and natural irritants such as poison ivy.
- inguinal hernia
- yeast infection
- swelling resulting from conditions external to the scrotum, including:
heart failure
kidney or liver disease
- heart failure
- kidney or liver disease
# Additional images
- Structure of the male genitalia.
- Vertical section of bladder, penis, and urethra.
- The superficial branches of the internal pudendal artery.
- A human scrotum, containing the testicles
A human scrotum, containing the testicles | https://www.wikidoc.org/index.php/Scrotum | |
ecc7fea7673877bed785490bd2519d02e00a4fa3 | wikidoc | Seafood | Seafood
# Overview
Seafood is any sea animal or seaweed that is served as food or is suitable for eating, particularly seawater animals, such as fish and shellfish (including mollusks and crustaceans). By extension, in North America although not generally in the United Kingdom, the term seafood is also applied to similar animals from fresh water and all edible aquatic animals are collectively referred to as seafood.
Edible seaweeds are rarely considered seafood, even though they come from seawater and are widely eaten around the world. See the category of sea vegetables.
The harvesting of seafood is known as fishing and the cultivation of seafood is known as aquaculture, mariculture, or simply fish farming.
Seafood is a source of protein in many diets around the world.
# Predicted collapse
Research into population trends of various species of seafood is pointing to a global collapse of seafood species by 2048. Such a collapse would occur due to pollution and overfishing, threatening oceanic ecosystems, according to some researchers.
A major international scientific study released in November 2006 in the journal Science found that about one-third of all fishing stocks worldwide have collapsed (with a collapse being defined as a decline to less than 10% of their maximum observed abundance), and that if current trends continue all fish stocks worldwide will collapse within fifty years.
The FAO State of World Fisheries and Aquaculture 2004 report estimates that in 2003, of the main fish stocks or groups of resources for which assessment information is available, "approximately one-quarter were overexploited, depleted or recovering from depletion (16%, 7% and 1% respectively) and needed rebuilding."
Advocacy organizations such as the National Fisheries Institute, however, disagree with such findings and assert that currently observed declines in fish population are due to natural fluctuations and that enhanced technologies will eventually alleviate whatever impact humanity is having on oceanic life.
# Dishes
- Bouillabaisse
- Fried calamari
- Ceviche
- Cioppino
- Clam chowder
- Shrimp cocktail
- Sashimi
- Sushi | Seafood
# Overview
Seafood is any sea animal or seaweed that is served as food or is suitable for eating, particularly seawater animals, such as fish and shellfish (including mollusks and crustaceans). By extension, in North America although not generally in the United Kingdom, the term seafood is also applied to similar animals from fresh water and all edible aquatic animals are collectively referred to as seafood.
Edible seaweeds are rarely considered seafood, even though they come from seawater and are widely eaten around the world. See the category of sea vegetables.
The harvesting of seafood is known as fishing and the cultivation of seafood is known as aquaculture, mariculture, or simply fish farming.
Seafood is a source of protein in many diets around the world.
# Predicted collapse
Research into population trends of various species of seafood is pointing to a global collapse of seafood species by 2048. Such a collapse would occur due to pollution and overfishing, threatening oceanic ecosystems, according to some researchers.[1]
A major international scientific study released in November 2006 in the journal Science found that about one-third of all fishing stocks worldwide have collapsed (with a collapse being defined as a decline to less than 10% of their maximum observed abundance), and that if current trends continue all fish stocks worldwide will collapse within fifty years.[2]
The FAO State of World Fisheries and Aquaculture 2004 report estimates that in 2003, of the main fish stocks or groups of resources for which assessment information is available, "approximately one-quarter were overexploited, depleted or recovering from depletion (16%, 7% and 1% respectively) and needed rebuilding."[3]
Advocacy organizations such as the National Fisheries Institute, however, disagree with such findings and assert that currently observed declines in fish population are due to natural fluctuations and that enhanced technologies will eventually alleviate whatever impact humanity is having on oceanic life.[4]
# Dishes
- Bouillabaisse
- Fried calamari
- Ceviche
- Cioppino
- Clam chowder
- Shrimp cocktail
- Sashimi
- Sushi | https://www.wikidoc.org/index.php/Seafood | |
b44504f20e4b19a179f9ffb10f2b12d21154c439 | wikidoc | Seaweed | Seaweed
Seaweeds are any of a large number of marine benthic algae. They are macroscopic and multicellular, in contrast with most other algae. Seaweeds areoften found in the seashore biome.
# Taxonomy
Seaweeds consist of several groups of multicellular algae: the red algae, green algae, and brown algae. As these three groups are not thought to have a common multicellular ancestor, the seaweeds are a paraphyletic group. In addition, tuft-forming bluegreen algae (Cyanobacteria) are sometimes considered as seaweeds.
Seaweeds are popularly described as plants, but only red and green algae belong to the kingdom Plantae). They should not be confused with aquatic plants such as seagrasses (which are vascular plants).
# Structure
Seaweeds' appearance somewhat resembles non-arboreal terrestrial plants.
- thallus: the algal body
lamina: a flattened structure that is somewhat leaf-like
sorus: spore cluster
-n Fucus, air bladders: float-assist organ (on blade)
-n kelp, floats: float-assist organ (between lamina and stipe)
stipe: a stem-like structure, may be absent
holdfast: specialized basal structure providing attachment to a surface, often a rock or another alga.
- lamina: a flattened structure that is somewhat leaf-like
sorus: spore cluster
-n Fucus, air bladders: float-assist organ (on blade)
-n kelp, floats: float-assist organ (between lamina and stipe)
- sorus: spore cluster
- on Fucus, air bladders: float-assist organ (on blade)
- on kelp, floats: float-assist organ (between lamina and stipe)
- stipe: a stem-like structure, may be absent
- holdfast: specialized basal structure providing attachment to a surface, often a rock or another alga.
The stipe and blade are collectively known as fronds.
# Ecology
The ecology of seaweeds is dominated by two specific environmental requirements. These are the presence of sea-water (or at least brackish water) and the presence of light sufficient to drive photosynthesis. A very common requirement is also to have a firm point of attachment. As a result, seaweeds are most commonly found in the littoral zone and within that zone more frequently on rocky shores than on sand or shingle. The ecological niches utilised by seaweeds are wide ranging. At the highest level are those that inhabit the zone that is only wetted by the tops of sea spray, the deepest living are those that are attached to the sea-bed under several meters of water. In some parts of the world, the area colonized by littoral seaweeds can extend for several miles away from the shore. The limiting factor in such cases is the availability of sufficient sun-light to support photosynthesis. The deepest living sea-weeds are the various kelps.
In addition to the familiar sea-shore seaweeds, a number of species have adapted to a fully planktonic niche and are free-floating, often with the assistance of gas filled sacs. Sargassum is one of the better know examples of this type of seaweed.
A number of species have adapted to the specialised environment of tidal rock pools. In this niche seaweeds are able to withstand rapidly changing temperature and salinity and even occasional drying.
# Uses
## Food
Seaweeds are extensively used as food by coastal peoples, particularly in East Asia, e.g. Japan, China, Korea, Taiwan, and Vietnam, but also in Indonesia, Peru, the Canadian Maritimes, Scandinavia, Ireland, Wales, Philippines, and Scotland, among other places. For example, Porphyra is a red alga used in Wales to make laverbread.
In Asia, nori is a food composed of sheets of dried Porphyra and is used in soups or to wrap sushi. Chondrus crispus (commonly known as Irish moss or carrageenan moss) is another red alga used in producing various food additives, along with Kappaphycus and various gigartinoid seaweeds. Laverbread made from oats and the seaweed laver is a popular dish in Wales.
Seaweeds are also harvested or cultivated for the extraction of alginate, agar and carrageenan, gelatinous substances collectively known as hydrocolloids or phycocolloids. Hydrocolloids have attained commercial significance, especially in food production as food additives. The food industry exploits the gelling, water-retention, emulsifying and other physical properties of these hydrocolloids. Agar is used in foods such as confectionery, meats and poultry products, desserts and beverages and moulded foods. Carrageenan is used in preparation of salad dressings and sauces, dietetic foods, and as a preservative in meat and fish products, dairy items and baked goods. Alginates enjoy many of the same uses as carrageenan, but are also used in production of industrial products such as paper coatings, adhesives, dyes, gels, explosives and in processes such as paper sizing, textile printing, hydro-mulching and drilling.
## Medicine
In the biomedicine and pharmaceutical industries, alginates are used in wound dressings, and production of dental moulds and have a host of other applications. In microbiology research, agar is extensively used as culture medium. Carrageenans, alginates and agaroses (the latter are prepared from agar by purification), together with other lesser-known macroalgal polysaccharides, also have several important biological activities or applications in biomedicine.
It has been asserted that seaweeds may have curative properties for tuberculosis, arthritis, colds and influenza, worm infestations and even tumors . A number of research studies have been conducted to investigate these claims and other effects of seaweed on human health .
See also Fucoidan
## Other uses
Other seaweeds may be used as seaweed fertilizer. | Seaweed
Seaweeds are any of a large number of marine benthic algae. They are macroscopic and multicellular, in contrast with most other algae. [1] Seaweeds areoften found in the seashore biome.
# Taxonomy
Seaweeds consist of several groups of multicellular algae: the red algae, green algae, and brown algae. As these three groups are not thought to have a common multicellular ancestor, the seaweeds are a paraphyletic group. In addition, tuft-forming bluegreen algae (Cyanobacteria) are sometimes considered as seaweeds.
Seaweeds are popularly described as plants, but only red and green algae belong to the kingdom Plantae). They should not be confused with aquatic plants such as seagrasses (which are vascular plants).
# Structure
Seaweeds' appearance somewhat resembles non-arboreal terrestrial plants.
- thallus: the algal body
lamina: a flattened structure that is somewhat leaf-like
sorus: spore cluster
on Fucus, air bladders: float-assist organ (on blade)
on kelp, floats: float-assist organ (between lamina and stipe)
stipe: a stem-like structure, may be absent
holdfast: specialized basal structure providing attachment to a surface, often a rock or another alga.
- lamina: a flattened structure that is somewhat leaf-like
sorus: spore cluster
on Fucus, air bladders: float-assist organ (on blade)
on kelp, floats: float-assist organ (between lamina and stipe)
- sorus: spore cluster
- on Fucus, air bladders: float-assist organ (on blade)
- on kelp, floats: float-assist organ (between lamina and stipe)
- stipe: a stem-like structure, may be absent
- holdfast: specialized basal structure providing attachment to a surface, often a rock or another alga.
The stipe and blade are collectively known as fronds.
# Ecology
The ecology of seaweeds is dominated by two specific environmental requirements. These are the presence of sea-water (or at least brackish water) and the presence of light sufficient to drive photosynthesis. A very common requirement is also to have a firm point of attachment. As a result, seaweeds are most commonly found in the littoral zone and within that zone more frequently on rocky shores than on sand or shingle. The ecological niches utilised by seaweeds are wide ranging. At the highest level are those that inhabit the zone that is only wetted by the tops of sea spray, the deepest living are those that are attached to the sea-bed under several meters of water. In some parts of the world, the area colonized by littoral seaweeds can extend for several miles away from the shore. The limiting factor in such cases is the availability of sufficient sun-light to support photosynthesis. The deepest living sea-weeds are the various kelps.
In addition to the familiar sea-shore seaweeds, a number of species have adapted to a fully planktonic niche and are free-floating, often with the assistance of gas filled sacs. Sargassum is one of the better know examples of this type of seaweed.
A number of species have adapted to the specialised environment of tidal rock pools. In this niche seaweeds are able to withstand rapidly changing temperature and salinity and even occasional drying. [2]
# Uses
## Food
Seaweeds are extensively used as food by coastal peoples, particularly in East Asia, e.g. Japan, China, Korea, Taiwan, and Vietnam, but also in Indonesia, Peru, the Canadian Maritimes, Scandinavia, Ireland, Wales, Philippines, and Scotland, among other places. For example, Porphyra is a red alga used in Wales to make laverbread.
In Asia, nori is a food composed of sheets of dried Porphyra and is used in soups or to wrap sushi. Chondrus crispus (commonly known as Irish moss or carrageenan moss) is another red alga used in producing various food additives, along with Kappaphycus and various gigartinoid seaweeds. Laverbread made from oats and the seaweed laver is a popular dish in Wales.
Seaweeds are also harvested or cultivated for the extraction of alginate, agar and carrageenan, gelatinous substances collectively known as hydrocolloids or phycocolloids. Hydrocolloids have attained commercial significance, especially in food production as food additives. [3] The food industry exploits the gelling, water-retention, emulsifying and other physical properties of these hydrocolloids. Agar is used in foods such as confectionery, meats and poultry products, desserts and beverages and moulded foods. Carrageenan is used in preparation of salad dressings and sauces, dietetic foods, and as a preservative in meat and fish products, dairy items and baked goods. Alginates enjoy many of the same uses as carrageenan, but are also used in production of industrial products such as paper coatings, adhesives, dyes, gels, explosives and in processes such as paper sizing, textile printing, hydro-mulching and drilling.
## Medicine
In the biomedicine and pharmaceutical industries, alginates are used in wound dressings, and production of dental moulds and have a host of other applications. In microbiology research, agar is extensively used as culture medium. Carrageenans, alginates and agaroses (the latter are prepared from agar by purification), together with other lesser-known macroalgal polysaccharides, also have several important biological activities or applications in biomedicine.[citation needed]
It has been asserted that seaweeds may have curative properties for tuberculosis, arthritis, colds and influenza, worm infestations and even tumors [1].[dubious – discuss] A number of research studies have been conducted to investigate these claims and other effects of seaweed on human health [2].[citation needed]
See also Fucoidan
## Other uses
Other seaweeds may be used as seaweed fertilizer. | https://www.wikidoc.org/index.php/Seaweed | |
1ec7e4e7befb2dde2d087403a8d1fbdf18ed46f1 | wikidoc | Sen-Sen | Sen-Sen
Sen-sen, marketed as a "breath perfume" is a type of breath freshener. In the early years of the twentieth century, before the health risks of tobacco were scientifically determined, Sen-sen was a commercial product that would "cover up" the smell of tobacco on one's breath and clothes at a time when there were just moral and personal reasons for disapproving of tobacco. Adolescent boys would use it, for instance, to attempt to hide from their parents the fact that they had been smoking. Thus did "Sen-sen" enter the list of moral faults caused by pocket-billiards in the song "Ya Got Trouble" in the musical comedy The Music Man. The product is mentioned in the Billy Joel song "Keeping the Faith." (I took a fresh pack of Luckies
And a mint called Sen-Sen.)
Sen-sen is mentioned in the book "Their Eyes Were Watching God" and referred to as also covering not only tobacco breath, but 'liquor breath'. It also was mentioned in the book "A Tree Grows in Brooklyn" as Hildy O'Dair had used it.
In Europe, there was a similar product oriented towards female smokers, called tabac blond.
# External link
- Sen-Sen, official website.
de:Sen-Sen | Sen-Sen
Sen-sen, marketed as a "breath perfume" is a type of breath freshener. In the early years of the twentieth century, before the health risks of tobacco were scientifically determined, Sen-sen was a commercial product that would "cover up" the smell of tobacco on one's breath and clothes at a time when there were just moral and personal reasons for disapproving of tobacco. Adolescent boys would use it, for instance, to attempt to hide from their parents the fact that they had been smoking. Thus did "Sen-sen" enter the list of moral faults caused by pocket-billiards in the song "Ya Got Trouble" in the musical comedy The Music Man. The product is mentioned in the Billy Joel song "Keeping the Faith." (I took a fresh pack of Luckies
And a mint called Sen-Sen.)
Sen-sen is mentioned in the book "Their Eyes Were Watching God" and referred to as also covering not only tobacco breath, but 'liquor breath'. It also was mentioned in the book "A Tree Grows in Brooklyn" as Hildy O'Dair had used it.
In Europe, there was a similar product oriented towards female smokers, called tabac blond.
## External link
- Sen-Sen, official website.
de:Sen-Sen
Template:Confection-stub
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Sen-Sen | |
983147752fd2e030675e89637a728df7419cebae | wikidoc | Senecio | Senecio
# Overview
Senecio (/sˈniːʃi.oʊ/)
is a genus of the daisy family (Asteraceae) that includes ragworts and groundsels. The flower heads are normally rayed, completely yellow, and the heads are borne in branched clusters. Senecio is one of the largest genera of flowering plants, and despite the separation of many species into other genera it still contains Template:Circa species of varied form, including leaf, stem and tuber succulents, annuals, perennials, aquatics, climbers, shrubs and small trees. Some species produce natural biocides (especially alkaloids) to deter or even kill animals that would eat them.
Senecio species are used as food plants by the larvae of some Lepidoptera species — see list of Lepidoptera that feed on Senecio.
Pyrrolizidine alkaloids have been found in Senecio nemorensis and in Senecio cannabifolius var. integrilifolius
The name means "old man".
# Selected species
- Senecio ampullaceus — Texas ragwort, Texas squaw-weed, Texas groundsel, clasping-leaf groundsel
- Senecio angulatus L.f. — Creeping groundsel
- Senecio antisanae
- Senecio arborescens
- Senecio aureus L. — Golden Ragwort
Packera aurea (L.) A. & D. Löve
- Packera aurea (L.) A. & D. Löve
- Senecio barbertonicus Klatt — Succulent Bush Senecio
- Senecio battiscombei
Dendrosenecio battiscombei
- Dendrosenecio battiscombei
- Senecio biglovii - Nodding groundsel
- Senecio brasiliensis (Spreng.) Less. — flor-das-almas
Cineraria brasiliensis
- Cineraria brasiliensis
- Senecio cambrensis — Welsh groundsel, Welsh ragwort
- Senecio congestus (R. Br.) DC. — Marsh ragwort, Clustered marsh ragwort, Marsh fleabane
Cineraria palustris
Othonna palustris
Tephroseris palustris
- Cineraria palustris
- Othonna palustris
- Tephroseris palustris
- Senecio douglasii - Threadleaf groundsel
- Senecio eboracensis Abbott & Lowe — York groundsel
- Senecio flaccidus Less. — Douglas senecio, threadleaf groundsel, threadleaf ragwort
- Senecio gallicus Chaix — Southern Ragwort
- Senecio glabellus Poir. — Butterweed
Packera glabella (Poir) C. Jeffrey
- Packera glabella (Poir) C. Jeffrey
- Senecio glaucus L. — Jaffa groundsel
- Senecio haworthii — Woolly senecio
- Senecio iscoensis — Hieron.
- Senecio jacobaea — Now classed as a separate genus with 29 species.
- Senecio keniensis
Dendrosenecio keniensis
- Dendrosenecio keniensis
- Senecio keniodendron — Giant groundsel
Dendrosenecio keniodendron
- Dendrosenecio keniodendron
- Senecio keniophytum
- Senecio kleinia
Kleinia neriifolia
- Kleinia neriifolia
- Senecio lamarckianus
- Senecio leucanthemifolius Poir. — Coastal Ragwort
- Senecio littoralis
- Senecio mikanioides — Cape Ivy, German Ivy
Delairea odorata
- Delairea odorata
- Senecio obovatus Muhl. — Roundleaf Ragwort
Packera obovata (Muhl. ex Willd.)
- Packera obovata (Muhl. ex Willd.)
- Senecio patagonicus
- Senecio pulcher
- Senecio rowleyanus — String of pearls
- Senecio sanmarcosensis
- Senecio scandens — German Ivy
- Senecio squalidus — Oxford ragwort
- Senecio triangularis - Arrowleaf groundsel
- Senecio vaginatus
- Senecio vernalis — Eastern groundsel
- Senecio viscosus — Sticky ragwort
- Senecio vulgaris — Common groundsel, old-man-in-the-spring
Formerly in Senecio
- Brachyglottis greyi (as S. greyi)
- Florist's Cineraria, Pericallis × hybrida (as S. cruentus)
- Rugelia nudicaulis — Rugels ragwort
# Synonyms
The following genera contain species that are or have been included within Senecio.
Probable synonyms:
- Antillanthus B. Nord.
- Barkleyanthus H. Rob. & Brettell
- Brachyglottis J. R. Forst. & G. Forst.
- Canariothamnus B. Nord.
- Dauresia B. Nord. & Pelser
- Dendrophorbium C. Jeffrey
- Dendrosenecio (Hauman ex Hedberg) B. Nord. - Giant groundsels
- Dorobaea Cass.
- Dresslerothamnus H. Rob.
- Elekmania B. Nord.
- Herreranthus B. Nord.
- Hubertia Bory
- Iocenes B. Nord.
- Jacobaea Mill.
- Lasiocephalus Willd. ex Schltdl.
- Leonis B. Nord.
- Lundinia B. Nord.
- Mesogramma DC.
- Monticalia C. Jeffrey
- Nelsonianthus H. Rob. & Brettell
- Nesampelos B. Nord., nom. inval.
- Oldfeltia B. Nord. & Lundin
- Packera Á. Löve & D. Löve
- Pentacalia Cass.
- Pippenalia McVaugh
- Pittocaulon H. Rob. & Brettell
- Pojarkovia Askerova
- Psacaliopsis H. Rob. & Brettell
- Pseudogynoxys (Greenm.) Cabrera
- Pseudojacobaea (Hook. f.) R. Mathur
- Roldana La Llave
- Sinosenecio B. Nord.
- Synotis (C. B. Clarke) C. Jeffrey & Y. L. Chen
- Telanthophora H. Rob. & Brettell
- Tephroseris (Rchb.) Rchb.
- Zemisia B. Nord. | Senecio
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Senecio (/[invalid input: 'icon']s[invalid input: 'ɨ']ˈniːʃi.oʊ/)[1]
is a genus of the daisy family (Asteraceae) that includes ragworts and groundsels. The flower heads are normally rayed, completely yellow, and the heads are borne in branched clusters. Senecio is one of the largest genera of flowering plants,[2] and despite the separation of many species into other genera it still contains Template:Circa species of varied form, including leaf, stem and tuber succulents, annuals, perennials, aquatics, climbers, shrubs and small trees. Some species produce natural biocides (especially alkaloids) to deter or even kill animals that would eat them.
Senecio species are used as food plants by the larvae of some Lepidoptera species — see list of Lepidoptera that feed on Senecio.
Pyrrolizidine alkaloids have been found in Senecio nemorensis[3] and in Senecio cannabifolius var. integrilifolius[4]
The name means "old man".
# Selected species
- Senecio ampullaceus — Texas ragwort, Texas squaw-weed, Texas groundsel, clasping-leaf groundsel[5]
- Senecio angulatus L.f. — Creeping groundsel
- Senecio antisanae
- Senecio arborescens
- Senecio aureus L. — Golden Ragwort[6]
Packera aurea (L.) A. & D. Löve
- Packera aurea (L.) A. & D. Löve
- Senecio barbertonicus Klatt — Succulent Bush Senecio
- Senecio battiscombei
Dendrosenecio battiscombei
- Dendrosenecio battiscombei
- Senecio biglovii - Nodding groundsel
- Senecio brasiliensis (Spreng.) Less. — flor-das-almas
Cineraria brasiliensis
- Cineraria brasiliensis
- Senecio cambrensis — Welsh groundsel, Welsh ragwort
- Senecio congestus (R. Br.) DC. — Marsh ragwort, Clustered marsh ragwort, Marsh fleabane
Cineraria palustris
Othonna palustris
Tephroseris palustris
- Cineraria palustris
- Othonna palustris
- Tephroseris palustris
- Senecio douglasii - Threadleaf groundsel
- Senecio eboracensis Abbott & Lowe — York groundsel
- Senecio flaccidus Less. — Douglas senecio, threadleaf groundsel, threadleaf ragwort
- Senecio gallicus Chaix — Southern Ragwort
- Senecio glabellus Poir. — Butterweed
Packera glabella (Poir) C. Jeffrey
- Packera glabella (Poir) C. Jeffrey
- Senecio glaucus L. — Jaffa groundsel
- Senecio haworthii — Woolly senecio
- Senecio iscoensis — Hieron.
- Senecio jacobaea — Now classed as a separate genus with 29 species.
- Senecio keniensis
Dendrosenecio keniensis
- Dendrosenecio keniensis
- Senecio keniodendron — Giant groundsel
Dendrosenecio keniodendron
- Dendrosenecio keniodendron
- Senecio keniophytum
- Senecio kleinia
Kleinia neriifolia
- Kleinia neriifolia
- Senecio lamarckianus
- Senecio leucanthemifolius Poir. — Coastal Ragwort
- Senecio littoralis
- Senecio mikanioides — Cape Ivy, German Ivy
Delairea odorata
- Delairea odorata
- Senecio obovatus Muhl. — Roundleaf Ragwort
Packera obovata (Muhl. ex Willd.)
- Packera obovata (Muhl. ex Willd.)
- Senecio patagonicus
- Senecio pulcher
- Senecio rowleyanus — String of pearls
- Senecio sanmarcosensis
- Senecio scandens — German Ivy[7]
- Senecio squalidus — Oxford ragwort
- Senecio triangularis - Arrowleaf groundsel
- Senecio vaginatus
- Senecio vernalis — Eastern groundsel
- Senecio viscosus — Sticky ragwort
- Senecio vulgaris — Common groundsel, old-man-in-the-spring
Formerly in Senecio
- Brachyglottis greyi (as S. greyi)
- Florist's Cineraria, Pericallis × hybrida (as S. cruentus)
- Rugelia nudicaulis — Rugels ragwort
# Synonyms
The following genera contain species that are or have been included within Senecio.[8]
Probable synonyms:
- Antillanthus B. Nord.
- Barkleyanthus H. Rob. & Brettell
- Brachyglottis J. R. Forst. & G. Forst.[9]
- Canariothamnus B. Nord.
- Dauresia B. Nord. & Pelser
- Dendrophorbium C. Jeffrey
- Dendrosenecio (Hauman ex Hedberg) B. Nord. - Giant groundsels
- Dorobaea Cass.
- Dresslerothamnus H. Rob.
- Elekmania B. Nord.
- Herreranthus B. Nord.
- Hubertia Bory
- Iocenes B. Nord.
- Jacobaea Mill.
- Lasiocephalus Willd. ex Schltdl.
- Leonis B. Nord.
- Lundinia B. Nord.
- Mesogramma DC.
- Monticalia C. Jeffrey
- Nelsonianthus H. Rob. & Brettell
- Nesampelos B. Nord., nom. inval.
- Oldfeltia B. Nord. & Lundin
- Packera Á. Löve & D. Löve
- Pentacalia Cass.
- Pippenalia McVaugh
- Pittocaulon H. Rob. & Brettell
- Pojarkovia Askerova
- Psacaliopsis H. Rob. & Brettell
- Pseudogynoxys (Greenm.) Cabrera
- Pseudojacobaea (Hook. f.) R. Mathur
- Roldana La Llave
- Sinosenecio B. Nord.
- Synotis (C. B. Clarke) C. Jeffrey & Y. L. Chen
- Telanthophora H. Rob. & Brettell
- Tephroseris (Rchb.) Rchb.
- Zemisia B. Nord.[10] | https://www.wikidoc.org/index.php/Senecio | |
85e7cbd48d9cf1311baaea9162fe3dd80e7ce773 | wikidoc | Seredyn | Seredyn
Seredyn, produced by BioNeurix Corporation, is marketed as a natural remedy used to treat anxiety, stress and insomnia. Utilizing 3 active ingredients, including two plant extracts and an amino acid, the makers claim to be able to reduce the symptoms of chronic anxiety, stress and fatigue. The product is a counterpart to another produced by the same company, Amoryn, which is aimed more towards patients who are seeking relief from depression, as well as anxiety. The makers claim it is safe to use both remedies at the same time. Because both Seredyn and Amoryn are natural remedies derived from plants, neither products are FDA approved, and are available without a prescription.
There is an Auto Ship Order system, but you cannot make any cancellation once you made.
# Active ingredients
- L-Theanine: An amino acid found in green tea.
- Passion flower: A plant extract, Passiflora incarnata, claimed to reduce symptoms of anxiety.
- Valerian: A plant extract, Valeriana officinalis, used as a sedative and relaxant.
# Possible side effects
Due to the possible sedative effects of this agent, patients just starting a regiment of Seredyn should be careful about operating a vehicle or operating machinery until one is familiar with the possible side effects, which include:
- Drowsiness
- Fatigue
- Stomach Upset
- Headache
- Increased sensitivity to sedative drugs
- Low blood pressure | Seredyn
Seredyn, produced by BioNeurix Corporation, is marketed as a natural remedy used to treat anxiety, stress and insomnia. Utilizing 3 active ingredients, including two plant extracts and an amino acid, the makers claim to be able to reduce the symptoms of chronic anxiety, stress and fatigue. The product is a counterpart to another produced by the same company, Amoryn, which is aimed more towards patients who are seeking relief from depression, as well as anxiety. The makers claim it is safe to use both remedies at the same time. Because both Seredyn and Amoryn are natural remedies derived from plants, neither products are FDA approved, and are available without a prescription.
There is an Auto Ship Order system, but you cannot make any cancellation once you made.
# Active ingredients
- L-Theanine: An amino acid found in green tea.
- Passion flower: A plant extract, Passiflora incarnata, claimed to reduce symptoms of anxiety.
- Valerian: A plant extract, Valeriana officinalis, used as a sedative and relaxant.
# Possible side effects
Due to the possible sedative effects of this agent, patients just starting a regiment of Seredyn should be careful about operating a vehicle or operating machinery until one is familiar with the possible side effects, which include:
- Drowsiness
- Fatigue
- Stomach Upset
- Headache
- Increased sensitivity to sedative drugs
- Low blood pressure
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Seredyn | |
6849eb7baccc0fe240beca595802938698648fd4 | wikidoc | Serovar | Serovar
A serovar or serotype is a grouping of microorganisms or viruses based on their cell surface antigens. Serovars allow organisms to be classified at the sub-species level; an issue of particular importance in epidemiology.
Serovars may be established based on virulence factors, lipopolysaccharides in Gram-negative bacteria, presence of an exotoxin (pertussis toxin in Bordetella pertussis, for example), plasmids, phages, or other characteristics which differentiate two members of the same species.
Salmonella, for example, has over 4400 serovars: Salmonella enterica serovar Typhimurium, S. enterica serovar Typhi, and S. enterica serovar Dublin, to name a few.
Vibrio cholerae, which causes cholera, has 139 serotypes, based on cell antigens. Only two of them produce an enterotoxin and are pathogens: 0:1 and 0:139.
Serotypes were discovered by the American microbiologist Rebecca Lancefield in 1933. | Serovar
A serovar or serotype is a grouping of microorganisms or viruses based on their cell surface antigens. Serovars allow organisms to be classified at the sub-species level; an issue of particular importance in epidemiology.[1]
Serovars may be established based on virulence factors, lipopolysaccharides in Gram-negative bacteria, presence of an exotoxin (pertussis toxin in Bordetella pertussis, for example), plasmids, phages, or other characteristics which differentiate two members of the same species. [1][2]
Salmonella, for example, has over 4400 serovars: Salmonella enterica serovar Typhimurium, S. enterica serovar Typhi, and S. enterica serovar Dublin, to name a few.[2]
Vibrio cholerae, which causes cholera, has 139 serotypes, based on cell antigens. Only two of them produce an enterotoxin and are pathogens: 0:1 and 0:139.
Serotypes were discovered by the American microbiologist Rebecca Lancefield in 1933.[3] | https://www.wikidoc.org/index.php/Serovar | |
1b2434da3dc4140db3ba77dc558f995cdc549e26 | wikidoc | Serutan | Serutan
Serutan was an early fiber-type laxative product which was widely promoted on U.S. radio and television from the 1930s through the 1960s. It was manufactured by the J. B. Williams Co., which was founded in 1885 and bought out by Nabisco in 1971.
The origin of the brand name was straightforward. The makers merely decided to spell "natures" backwards, and "Read it backwards" was the product's advertising slogan. This was to differentiate it as being a "natural" product as opposed to laxative brands which stimulated the colon by chemical action rather than sheer bulk of contents.
The product was almost uniformly promoted on programs whose core audience as shown by demographics was known to be considerably older than that of the typical television viewer. Serutan is especially associated with The Lawrence Welk Show and The Original Amateur Hour, both of which were also sponsored by J. B. Williams products Sominex, a sleeping pill and Geritol, a vitamin supplement. Serutan was the target of numerous jokes by radio comedians during the 1930s and 1940s.
"Serutan Approach" is also a trend within the positivist definition of Science.
# Listen to
- Red Ingle sings "Serutan Yob (A Song for Backward Boys and Girls under 40)" | Serutan
Serutan was an early fiber-type laxative product which was widely promoted on U.S. radio and television from the 1930s through the 1960s. It was manufactured by the J. B. Williams Co., which was founded in 1885 and bought out by Nabisco in 1971.
The origin of the brand name was straightforward. The makers merely decided to spell "natures" backwards, and "Read it backwards" was the product's advertising slogan. This was to differentiate it as being a "natural" product as opposed to laxative brands which stimulated the colon by chemical action rather than sheer bulk of contents.
The product was almost uniformly promoted on programs whose core audience as shown by demographics was known to be considerably older than that of the typical television viewer. Serutan is especially associated with The Lawrence Welk Show and The Original Amateur Hour, both of which were also sponsored by J. B. Williams products Sominex, a sleeping pill and Geritol, a vitamin supplement. Serutan was the target of numerous jokes by radio comedians during the 1930s and 1940s.
"Serutan Approach" is also a trend within the positivist definition of Science.
# Listen to
- Red Ingle sings "Serutan Yob (A Song for Backward Boys and Girls under 40)"
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Serutan | |
b46f434d168c3b38098b2f15b2184ffac3ae4ca6 | wikidoc | Sextasy | Sextasy
- REDIRECT Template:Nofootnotes
Sextasy is a common name for a drug combination of ecstacy (methylenedioxymethamphetamine), and sildenafil citrate (Viagra), which is a PDE5 inhibitor and vasodilator used for erectile dysfunction. Sextasy can be ingested as two separate mediums (such as tablets) or they may be crushed and combined for insufflation or insertion into a capsule. Sextasy is a slang term for the combination, referring to ecstasy and sex combined, Viagra allows the user to achieve an erection, a difficult feat due to the strong stimulant nature of ecstasy.
# Physiological Interactions
Sextasy's inclusion of Viagra is thought to minimize or eliminate the effect of MDMA (Ecstasy) on the ability to develop an erection. Ecstasy affects areas in the brain that ultimately induce a significant period of euphoria, the mechanism of which is believed to trigger a massive amount of serotonin to flood the neuroreceptors.
# Risks
Immediate psychological effects last from four to six hours and may include euphoria, anxiety, insomnia, and/or paranoia. Immediate physical effects include muscle tension, jaw clenching, nausea, nystagmus (involuntary eye movement), tremors, increased heart rate, and chills. Due to increases in heart rate and blood pressure, a user's body temperature may effectively rise and lead to dehydration, hyperthermia, and possible seizures.
Since PDE5 inhibitors work by vasodilation, headaches are a common side effect of PDE5 inhibitors alone. Viagra alone can in some patients cause priapism, an erection that lasts more than four hours. Priapism is painful and can cause lasting damage to the penis. | Sextasy
- REDIRECT Template:Nofootnotes
Sextasy is a common name for a drug combination of ecstacy (methylenedioxymethamphetamine), and sildenafil citrate (Viagra), which is a PDE5 inhibitor and vasodilator used for erectile dysfunction. Sextasy can be ingested as two separate mediums (such as tablets) or they may be crushed and combined for insufflation or insertion into a capsule. Sextasy is a slang term for the combination, referring to ecstasy and sex combined, Viagra allows the user to achieve an erection, a difficult feat due to the strong stimulant nature of ecstasy.
# Physiological Interactions
Sextasy's inclusion of Viagra is thought to minimize or eliminate the effect of MDMA (Ecstasy) on the ability to develop an erection. Ecstasy affects areas in the brain that ultimately induce a significant period of euphoria, the mechanism of which is believed to trigger a massive amount of serotonin to flood the neuroreceptors.
# Risks
Immediate psychological effects last from four to six hours and may include euphoria, anxiety, insomnia, and/or paranoia.[citation needed] Immediate physical effects include muscle tension, jaw clenching, nausea, nystagmus (involuntary eye movement), tremors, increased heart rate, and chills.[citation needed] Due to increases in heart rate and blood pressure, a user's body temperature may effectively rise and lead to dehydration, hyperthermia, and possible seizures.[citation needed]
Since PDE5 inhibitors work by vasodilation, headaches are a common side effect of PDE5 inhibitors alone. Viagra alone can in some patients cause priapism, an erection that lasts more than four hours. Priapism is painful and can cause lasting damage to the penis. [1] | https://www.wikidoc.org/index.php/Sextasy | |
971c91a71719be53bb2e0ad3901450d4205bbeb0 | wikidoc | Shampoo | Shampoo
Shampoo is a common hair care product used for the removal of oils, dirt, skin particles, dandruff, environmental pollutants and other contaminant particles that gradually build up in hair. The goal is to remove the unwanted build-up without stripping out so much as to make hair unmanageable.
Shampoo, when lathered with water, is a surfactant, which, while cleaning the hair and scalp, can remove the natural oils (sebum) which lubricate the hair shaft.
Shampooing is frequently followed by conditioners which increase the ease of combing and styling.
# History
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.
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. His baths were like Turkish baths where clients received an Indian treatment of champi (shampooing) or therapeutic massage. His service was appreciated; he received the high accolade of being appointed ‘Shampooing Surgeon’ to both George IV and William IV.
During the early stages of shampoo, English hair stylists boiled shaved soap in water and added herbs to give the hair shine and fragrance. Kasey Hebert was the first known maker of shampoo, and the origin is currently attributed to him.
Originally, soap and shampoo were very similar products; both containing surfactants, a type of detergent. Modern shampoo as it is known today was first introduced in the 1930s with Drene, the first synthetic (non-soap) shampoo.
From ancient times to this day, Indians have been using different formulations of shampoos using herbs like neem, shikakai or soapnut, henna, bael, brahmi, fenugreek, buttermilk, amla, aloe, and almond in combination with some aromatic components like sandalwood, jasmine, turmeric, rose, and musk.
# How shampoo works
Shampoo cleans by stripping sebum from the hair. Sebum is an oil secreted by hair follicles that is readily absorbed by the strands of hair, and forms a protective layer. Sebum protects the protein structure of hair from damage, but this protection comes at a cost. It tends to collect dirt, styling products and scalp flakes. Surfactants strip the sebum from the hair shafts and thereby remove the dirt attached to it.
While both soaps and shampoos contain surfactants, soap bonds to oils with such affinity that it removes too much if used on hair. Shampoo uses a different class of surfactants balanced to avoid removing too much oil from the hair.
The chemical mechanisms that underlie hair cleansing are similar to that of traditional soap. Undamaged hair has a hydrophobic surface to which skin lipids such as sebum stick, but water is initially repelled. The lipids do not come off easily when the hair is rinsed with plain water. The anionic surfactants substantially reduce the interfacial surface tension and allow for the removal of the sebum from the hair shaft. The non-polar oily materials on the hair shaft are solubilised into the surfactant micelle structures of the shampoo and are removed during rinsing. There is also considerable removal through a surfactant and oil "roll up" effect. The foamy effect achieved by massaging shampoo into the hair is purely aesthetic.
# Composition
Shampoo formulations seek to maximize the following qualities:
- Easy rinsing
- Good finish after washing hair
- Minimal skin/eye irritation
- No damage to hair
- Feels thick and/or creamy
- Pleasant fragrance
- Low toxicity
- Good biodegradability
- Slightly acidic (pH less than 7), since a basic environment weakens the hair by breaking the disulfide bonds in hair keratin.
Many shampoos are pearlescent. This effect is achieved by addition of tiny flakes of suitable materials, eg. glycol distearate, chemically derived from stearic acid, which may have either animal or vegetable origins. Glycol distearate is a wax.
# Ingredient claims
In the USA, the Food and Drug Administration (FDA) mandates that shampoo containers accurately list ingredients. The government further regulates what shampoo manufacturers can and cannot claim as any associated benefit. Shampoo producers often use these regulations to challenge marketing claims made by competitors, helping to enforce these regulations. While the claims may be substantiated however, the testing methods and details of such claims are not as straightforward. For example, many products are purported to protect hair from damage due to ultraviolet radiation. While the ingredient responsible for this protection does block UV, it is not present in a high enough concentration to be effective. Shampoos made for treating medical conditions such as dandruff are regulated as OTC drugs.
## Vitamins and Amino Acids
The effectiveness of vitamins, amino acids and "pro-vitamins" to shampoo is also largely debatable. Vitamins and amino acids are the building blocks of proteins and enzymes within the body. While vitamins may be able to penetrate cells through the skin, amino acids and proteins are too large to enter a cell outside the bloodstream, and they can have no effect on dead tissue. Proteins are constructed from amino acids following an RNA blueprint inside the cell. A strand of hair is a long protein chain continually being added to at the root. The only way for an amino acid to be of any use is to be intentionally bound to other amino acids in a specific fashion by a living cell. Hair is not alive, and there is no possibility for an amino acid or protein to have any permanent effect on the health of the strand.
The case for vitamins is not as well understood. Some have demonstrated a moderate effectiveness in improving the health of skin, but most likely the benefit is derived from the effect of vitamins on living cells below the epidermis. Extending this benefit to hair, the vitamins and minerals could improve the health of new hair growth, but the benefit to existing hair is unsubstantiated. However, the physical properties of some vitamins (like vitamin E oil or panthenol) would have a temporary cosmetic effect on the hair shaft while not having any bioactivity.
# Specialized shampoos
## Dandruff
Cosmetic companies have developed shampoos specifically for those who have dandruff. These contain fungicides such as zinc pyrithione and selenium sulfide which reduce loose dander by killing Malassezia furfur. Coal tar and salicylate derivatives are often used as well.
## All-natural
Some companies use "all-natural", "organic", "botanical", or "plant-derived" ingredients (such as plant extracts or oils), combining these additions with one or more typical surfactants. The effectiveness of these organic ingredients is disputed.
Alternative shampoos, sometimes labeled SLS-free, have fewer harsh chemicals -
typically none from the sulfate family. They are claimed to be gentler on human hair.
## Baby
Shampoo for infants and young children is formulated so that it is less irritating and usually less prone to produce a stinging or burning sensation if it were to get into the eyes. This is accomplished by one or more of the following formulation strategies:
- dilution, in case product comes in contact with eyes after running off the top of the head with minimal further dilution;
- adjusting pH to that of non-stress tears, approximately 7, which may be a higher pH than that of shampoos which are pH adjusted for skin or hair effects, and lower than that of shampoo made of soap;
- use of surfactants which, alone or in combination, are less irritating than those used in other shampoos;
- use of nonionic surfactants of the form of polyethoxylated synthetic glycolipids and/or polyethoxylated synthetic monoglycerides, which surfactants counteract the eye sting of other surfactants without producing the anesthetizing effect of alkyl polyethoxylates or alkylphenol polyethoxylates.
The distinction in 4 above does not completely surmount controversy over the use of shampoo ingredients to mitigate eye sting produced by other ingredients, or of use of the products so formulated.
The considerations in 3 and 4 frequently result in a much greater multiplicity of surfactants being used in individual baby shampoos than in other shampoos, and the detergency and/or foaming of such products may be compromised thereby. The monoanionic sulfonated surfactants and viscosity-increasing or foam stabilizing alkanolamides seen so frequently in other shampoos are much less common in the better baby shampoos.
## Animal
Shampoo for animals (such as for dogs or cats) should be formulated especially for them, as their skin has fewer cell layers than human skin. Cats' skin is 2-3 cell layers thick, while dogs' skin is 3-5 layers. Human skin, by contrast, is 10-15 cell layers thick. This is a clear example of why one should never use even something as mild as baby shampoo on a cat, dog, or other pet.
Shampoo intended for animals may contain insecticides or other medications for treatment of skin conditions or parasite infestations such as fleas or mange. These must never be used on humans! It is equally important to note that while some human shampoos may be harmless when used on animals, any haircare products that contain active ingredients/drugs (such as zinc in antidandruff shampoos) are potentially toxic when ingested by animals. Special care must be taken not to use those products on pets. Cats are at particular risk due to their instinctive method of grooming their fur with their tongues.
## Solid
Solid shampoos or shampoo bars use as their surfactants soaps and/or other surfactants conveniently formulated as solids. They have the advantage of being spill-proof, and the disadvantage of being slowly applied, needing to be dissolved in use.
## Jelly/Gel
Stiff, non-pourable clear gels to be squeezed from a tube were once popular forms of shampoo, and can be made by an increase of the method used to increase viscosity of liquid products. Their containers could not be spilled, but unlike solids, they could still be lost down the drain by sliding off wet skin or hair. Formerly soap jelly was made at home by dissolving sodium soap in hot water ahead of the time it would be used for shampooing or other purposes, to avoid problem of slow application of solids noted above.
## Paste/cream
Shampoos in the form of pastes or creams were formerly marketed in jars or tubes. The contents were wet but not completely dissolved. They would apply faster than solids and dissolve quickly. Jar contents were prone to contamination by users and hence had to be very well preserved.
# Traditional Shampoos
## Indonesia
Early shampoos used in Indonesia were made from the husk and straw (merang) of rice. The husks and straws were burned into ash, and the ashes (which have alkaline properties) are mixed with water to form lather. The ashes and lather were scrubbed into the hair and rinsed out, leaving the hair clean, but very dry. Afterwards, coconut oil was applied to the hair in order to moisturize it. | Shampoo
Shampoo is a common hair care product used for the removal of oils, dirt, skin particles, dandruff, environmental pollutants and other contaminant particles that gradually build up in hair. The goal is to remove the unwanted build-up without stripping out so much as to make hair unmanageable.
Shampoo, when lathered with water, is a surfactant, which, while cleaning the hair and scalp, can remove the natural oils (sebum) which lubricate the hair shaft.
Shampooing is frequently followed by conditioners which increase the ease of combing and styling.
# History
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.
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. His baths were like Turkish baths where clients received an Indian treatment of champi (shampooing) or therapeutic massage. His service was appreciated; he received the high accolade of being appointed ‘Shampooing Surgeon’ to both George IV and William IV.
During the early stages of shampoo, English hair stylists boiled shaved soap in water and added herbs to give the hair shine and fragrance. Kasey Hebert was the first known maker of shampoo, and the origin is currently attributed to him.
Originally, soap and shampoo were very similar products; both containing surfactants, a type of detergent. Modern shampoo as it is known today was first introduced in the 1930s with Drene, the first synthetic (non-soap) shampoo.[1]
From ancient times to this day, Indians have been using different formulations of shampoos using herbs like neem, shikakai or soapnut, henna, bael, brahmi, fenugreek, buttermilk, amla, aloe, and almond in combination with some aromatic components like sandalwood, jasmine, turmeric, rose, and musk.
# How shampoo works
Shampoo cleans by stripping sebum from the hair. Sebum is an oil secreted by hair follicles that is readily absorbed by the strands of hair, and forms a protective layer. Sebum protects the protein structure of hair from damage, but this protection comes at a cost. It tends to collect dirt, styling products and scalp flakes. Surfactants strip the sebum from the hair shafts and thereby remove the dirt attached to it.
While both soaps and shampoos contain surfactants, soap bonds to oils with such affinity that it removes too much if used on hair. Shampoo uses a different class of surfactants balanced to avoid removing too much oil from the hair.
The chemical mechanisms that underlie hair cleansing are similar to that of traditional soap. Undamaged hair has a hydrophobic surface to which skin lipids such as sebum stick, but water is initially repelled. The lipids do not come off easily when the hair is rinsed with plain water. The anionic surfactants substantially reduce the interfacial surface tension and allow for the removal of the sebum from the hair shaft. The non-polar oily materials on the hair shaft are solubilised into the surfactant micelle structures of the shampoo and are removed during rinsing. There is also considerable removal through a surfactant and oil "roll up" effect. The foamy effect achieved by massaging shampoo into the hair is purely aesthetic.
# Composition
Shampoo formulations seek to maximize the following qualities:
- Easy rinsing
- Good finish after washing hair
- Minimal skin/eye irritation
- No damage to hair
- Feels thick and/or creamy
- Pleasant fragrance
- Low toxicity
- Good biodegradability
- Slightly acidic (pH less than 7), since a basic environment weakens the hair by breaking the disulfide bonds in hair keratin.
Many shampoos are pearlescent. This effect is achieved by addition of tiny flakes of suitable materials, eg. glycol distearate, chemically derived from stearic acid, which may have either animal or vegetable origins. Glycol distearate is a wax.
# Ingredient claims
In the USA, the Food and Drug Administration (FDA) mandates that shampoo containers accurately list ingredients. The government further regulates what shampoo manufacturers can and cannot claim as any associated benefit. Shampoo producers often use these regulations to challenge marketing claims made by competitors, helping to enforce these regulations. While the claims may be substantiated however, the testing methods and details of such claims are not as straightforward. For example, many products are purported to protect hair from damage due to ultraviolet radiation. While the ingredient responsible for this protection does block UV, it is not present in a high enough concentration to be effective. Shampoos made for treating medical conditions such as dandruff are regulated as OTC drugs.[2]
## Vitamins and Amino Acids
The effectiveness of vitamins, amino acids and "pro-vitamins" to shampoo is also largely debatable. Vitamins and amino acids are the building blocks of proteins and enzymes within the body. While vitamins may be able to penetrate cells through the skin, amino acids and proteins are too large to enter a cell outside the bloodstream, and they can have no effect on dead tissue. Proteins are constructed from amino acids following an RNA blueprint inside the cell. A strand of hair is a long protein chain continually being added to at the root. The only way for an amino acid to be of any use is to be intentionally bound to other amino acids in a specific fashion by a living cell. Hair is not alive, and there is no possibility for an amino acid or protein to have any permanent effect on the health of the strand.
The case for vitamins is not as well understood. Some have demonstrated a moderate effectiveness in improving the health of skin,[3] but most likely the benefit is derived from the effect of vitamins on living cells below the epidermis. Extending this benefit to hair, the vitamins and minerals could improve the health of new hair growth, but the benefit to existing hair is unsubstantiated. However, the physical properties of some vitamins (like vitamin E oil or panthenol) would have a temporary cosmetic effect on the hair shaft while not having any bioactivity.
# Specialized shampoos
## Dandruff
Cosmetic companies have developed shampoos specifically for those who have dandruff. These contain fungicides such as zinc pyrithione and selenium sulfide which reduce loose dander by killing Malassezia furfur. Coal tar and salicylate derivatives are often used as well.
## All-natural
Some companies use "all-natural", "organic", "botanical", or "plant-derived" ingredients (such as plant extracts or oils), combining these additions with one or more typical surfactants. The effectiveness of these organic ingredients is disputed.
Alternative shampoos, sometimes labeled SLS-free, have fewer harsh chemicals -
typically none from the sulfate family. They are claimed to be gentler on human hair.
## Baby
Shampoo for infants and young children is formulated so that it is less irritating and usually less prone to produce a stinging or burning sensation if it were to get into the eyes. This is accomplished by one or more of the following formulation strategies:
- dilution, in case product comes in contact with eyes after running off the top of the head with minimal further dilution;
- adjusting pH to that of non-stress tears, approximately 7, which may be a higher pH than that of shampoos which are pH adjusted for skin or hair effects, and lower than that of shampoo made of soap;
- use of surfactants which, alone or in combination, are less irritating than those used in other shampoos;
- use of nonionic surfactants of the form of polyethoxylated synthetic glycolipids and/or polyethoxylated synthetic monoglycerides, which surfactants counteract the eye sting of other surfactants without producing the anesthetizing effect of alkyl polyethoxylates or alkylphenol polyethoxylates.
The distinction in 4 above does not completely surmount controversy over the use of shampoo ingredients to mitigate eye sting produced by other ingredients, or of use of the products so formulated.
The considerations in 3 and 4 frequently result in a much greater multiplicity of surfactants being used in individual baby shampoos than in other shampoos, and the detergency and/or foaming of such products may be compromised thereby. The monoanionic sulfonated surfactants and viscosity-increasing or foam stabilizing alkanolamides seen so frequently in other shampoos are much less common in the better baby shampoos. [1]
## Animal
Shampoo for animals (such as for dogs or cats) should be formulated especially for them, as their skin has fewer cell layers than human skin. Cats' skin is 2-3 cell layers thick, while dogs' skin is 3-5 layers. Human skin, by contrast, is 10-15 cell layers thick. This is a clear example of why one should never use even something as mild as baby shampoo on a cat, dog, or other pet.
Shampoo intended for animals may contain insecticides or other medications for treatment of skin conditions or parasite infestations such as fleas or mange. These must never be used on humans! It is equally important to note that while some human shampoos may be harmless when used on animals, any haircare products that contain active ingredients/drugs (such as zinc in antidandruff shampoos) are potentially toxic when ingested by animals. Special care must be taken not to use those products on pets. Cats are at particular risk due to their instinctive method of grooming their fur with their tongues.
## Solid
Solid shampoos or shampoo bars use as their surfactants soaps and/or other surfactants conveniently formulated as solids. They have the advantage of being spill-proof, and the disadvantage of being slowly applied, needing to be dissolved in use.
## Jelly/Gel
Stiff, non-pourable clear gels to be squeezed from a tube were once popular forms of shampoo, and can be made by an increase of the method used to increase viscosity of liquid products. Their containers could not be spilled, but unlike solids, they could still be lost down the drain by sliding off wet skin or hair. Formerly soap jelly was made at home by dissolving sodium soap in hot water ahead of the time it would be used for shampooing or other purposes, to avoid problem of slow application of solids noted above.
## Paste/cream
Shampoos in the form of pastes or creams were formerly marketed in jars or tubes. The contents were wet but not completely dissolved. They would apply faster than solids and dissolve quickly. Jar contents were prone to contamination by users and hence had to be very well preserved.
# Traditional Shampoos
## Indonesia
Early shampoos used in Indonesia were made from the husk and straw (merang) of rice. The husks and straws were burned into ash, and the ashes (which have alkaline properties) are mixed with water to form lather. The ashes and lather were scrubbed into the hair and rinsed out, leaving the hair clean, but very dry. Afterwards, coconut oil was applied to the hair in order to moisturize it.[4] | https://www.wikidoc.org/index.php/Shampoo | |
15c089964c6cb1d8da7daff9f0b3b1010f279f9a | wikidoc | Shyness | Shyness
In humans, shyness is the feeling of apprehension or lack of confidence experienced in regard to social association with others, e.g. being in proximity to, approaching and being approached by others. In zoology, shy generally means "tends to avoid human beings"; See crypsis. Shyness in animals manifests with ostensibly similar behavioral traits, but differs wholly from humans in cognition and motivation.
# Triggers, traits and misperception
Shyness is most likely to occur during unfamiliar situations, though in severe cases it may hinder an individual in his or her most familiar situations and relationships as well. Shy individuals avoid the objects of their apprehension in order to avoid feeling uncomfortable and inept, thus the situations remain unfamiliar and the shyness perpetuates itself. Shyness may fade with time (a child who is shy toward strangers, for instance, may eventually lose this trait when older and more socially adept), or may be an integrated, life-long character trait, often by adolescence and young adulthood (but most likely around the age of 13).
Humans experience shyness to different degrees and in different areas. For example, an actor may be loud and bold on stage, but shy in an interview. In addition, shyness may manifest when one is in the company of certain people and completely disappear when with others—one may be outgoing with friends and family, but experience love-shyness toward potential partners, even if strangers are generally not an obstacle.
The condition of true shyness may simply involve the discomfort of difficulty in knowing what to say in social situations, or may include crippling physical manifestations of uneasiness. Shyness usually involves a combination of both symptoms, and may be quite devastating for the sufferer, in many cases leading them to feel that they are boring, or exhibit bizarre behaviour in an attempt to create interest, alienating them further.
Instinctive behavioural traits in social situations such as smiling, easily producing suitable conversational topics, assuming a relaxed posture and making good eye contact, which come spontaneously for the average person, may not be second nature for a shy person, requiring struggle or being completely unattainable.
## Complications
The term shyness may be implemented as a lay blanket-term for a family of related and partially overlapping afflictions, including timidity (apprehension in meeting new people), bashfulness and diffidence (lack of assertiveness), apprehension and anticipation (general fear of potential interaction), or intimidation (relating to the object of fear rather than one's low confidence).
It must also be noted that apparent shyness, as perceived by others, may simply be the manifestation of reservation or introversion, character traits which cause an individual to voluntarily avoid excessive social contact or be terse in communication, but are not motivated or accompanied by discomfort, apprehension, or lack of confidence.
Rather, according to Bernardo J. Carducci, director of the Shyness Research Institute, introverts choose to avoid social situations because they derive no reward from them, or may find surplus sensory input overwhelming. Conversely, shy people fear such situations and feel that they must avoid them.
Shy people tend to perceive their own shyness as a negative trait, and many people are uneasy with shyness in others, especially in cultures which value individuality and taking charge. This generally poor reception of shyness may be misinterpreted by the suffering individual as aversion related to his or her personality, rather than simply to his or her shyness. Both conditions can lead to a compounding of a shy individual's low self-confidence.
In American culture, which tends to value outspokenness and confidence, a shy individual could be perceived as weak. To an unsympathetic observer, a shy individual may be mistaken as arrogant or aloof, frustrating the sufferer. In more forgiving arenas, shy people may be perceived to be thoughtful, good listeners and are more likely to think before they speak. Furthermore, boldness, the opposite of shyness, may cause its own problems, such as impertinence or inappropriate behavior.
# Origins
The initial causes of shyness vary. Scientists have located some genetic data that supports the hypothesis that shyness is at least partially genetic. However, there is also evidence that the environment in which a person is raised can affect their shyness. This includes child abuse, particularly emotional abuse such as ridicule. Shyness can originate after a person has experienced a physical anxiety reaction; at other times, shyness seems to develop first and then later causes physical symptoms of anxiety.
Shyness differs from social anxiety, which is a broader, often depression-related psychological condition including the experience of fear, apprehension or worry regarding social situations and being evaluated by others to panic-inducing extents.
# Genetics and heredity
The genetics of shyness is a relatively small area of research that has been receiving an even smaller amount of attention, although papers on the biological bases of shyness date back at least to 1988.
Some research has indicated that shyness and aggression are related—through long and short forms of the gene DRD4, though considerably more research on this is needed. Further, it has been suggested that shyness and social phobia (the distinction between the two is becoming ever more blurred) are related to obsessive-compulsive disorder.
As with other studies of behavioral genetics, the study of shyness is complicated by the number of genes involved in, and the confusion in defining, the phenotype. Naming the phenotype – and translation of terms between genetics and psychology — also causes problems. In some research, "behavioral inhibition" is studied, in others anxiety or social inhibition is. One solution to this problem is to study the genetics of underlying traits, such as "anxious temperament."
Several genetic links to shyness are current areas of research. One of the most promising is the serotonin transporter promoter region polymorphism (5-HTTLPR), the long form of which has been shown to be highly correlated with shyness in grade school children. Previous studies had shown a connection between this form of the gene and both obsessive-compulsive disorder and autism. Mouse models have also been used, to derive genes suitable for further study in humans; one such gene, the glutamic acid decarboxylase gene (which encodes an enzyme that functions in GABA synthesis), has so far been shown to have some association with behavioral inhibition. Another gene, the dopamine D4 receptor gene (DRD4) exon III polymorphism, had been the subject of studies in both shyness and aggression, and is currently the subject of studies on the "novelty seeking" trait. A 1996 study of anxiety-related traits (shyness being one of these) remarked that, "Although twin studies have indicated that individual variation in measures of anxiety-related personality traits is 40-60% heritable, none of the relevant genes has yet been identified," and that "10 to 15 genes might be predicted to be involved" in the anxiety trait. Progress has been made since then, especially in identifying other potential genes involved in personality traits, but there has been little progress made towards confirming these relationships. The long version of the 5-HTT gene-linked polymorphic region (5-HTTLPR) is now postulated to be correlated with shyness, but in the 1996 study, the short version was shown to be related to anxiety-based traits. This confusion and contradiction does not oppose the genetic basis of personality traits, but does emphasize the amount of research there is still to be done before the bases of even one or two of these characteristics can be identified.
# Environmental factors
Excessive shyness, embarrassment, self consciousness and timidity, social-phobia and lack of self-confidence are also components of erethism, which is a symptom complex that appears in cases of mercury poisoning. | Shyness
Template:Search infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
In humans, shyness is the feeling of apprehension or lack of confidence experienced in regard to social association with others, e.g. being in proximity to, approaching and being approached by others. In zoology, shy generally means "tends to avoid human beings"; See crypsis. Shyness in animals manifests with ostensibly similar behavioral traits, but differs wholly from humans in cognition and motivation.
# Triggers, traits and misperception
Shyness is most likely to occur during unfamiliar situations, though in severe cases it may hinder an individual in his or her most familiar situations and relationships as well. Shy individuals avoid the objects of their apprehension in order to avoid feeling uncomfortable and inept, thus the situations remain unfamiliar and the shyness perpetuates itself. Shyness may fade with time (a child who is shy toward strangers, for instance, may eventually lose this trait when older and more socially adept), or may be an integrated, life-long character trait, often by adolescence and young adulthood (but most likely around the age of 13).
Humans experience shyness to different degrees and in different areas. For example, an actor may be loud and bold on stage, but shy in an interview. In addition, shyness may manifest when one is in the company of certain people and completely disappear when with others—one may be outgoing with friends and family, but experience love-shyness toward potential partners, even if strangers are generally not an obstacle.
The condition of true shyness may simply involve the discomfort of difficulty in knowing what to say in social situations, or may include crippling physical manifestations of uneasiness. Shyness usually involves a combination of both symptoms, and may be quite devastating for the sufferer, in many cases leading them to feel that they are boring, or exhibit bizarre behaviour in an attempt to create interest, alienating them further.
Instinctive behavioural traits in social situations such as smiling, easily producing suitable conversational topics, assuming a relaxed posture and making good eye contact, which come spontaneously for the average person, may not be second nature for a shy person, requiring struggle or being completely unattainable.
## Complications
The term shyness may be implemented as a lay blanket-term for a family of related and partially overlapping afflictions, including timidity (apprehension in meeting new people), bashfulness and diffidence (lack of assertiveness), apprehension and anticipation (general fear of potential interaction), or intimidation (relating to the object of fear rather than one's low confidence).[2]
It must also be noted that apparent shyness, as perceived by others, may simply be the manifestation of reservation or introversion, character traits which cause an individual to voluntarily avoid excessive social contact or be terse in communication, but are not motivated or accompanied by discomfort, apprehension, or lack of confidence.
Rather, according to Bernardo J. Carducci, director of the Shyness Research Institute, introverts choose to avoid social situations because they derive no reward from them, or may find surplus sensory input overwhelming. Conversely, shy people fear such situations and feel that they must avoid them. [3]
Shy people tend to perceive their own shyness as a negative trait, and many people are uneasy with shyness in others, especially in cultures which value individuality and taking charge. This generally poor reception of shyness may be misinterpreted by the suffering individual as aversion related to his or her personality, rather than simply to his or her shyness. Both conditions can lead to a compounding of a shy individual's low self-confidence.
In American culture, which tends to value outspokenness and confidence, a shy individual could be perceived as weak. To an unsympathetic observer, a shy individual may be mistaken as arrogant or aloof, frustrating the sufferer. In more forgiving arenas, shy people may be perceived to be thoughtful, good listeners and are more likely to think before they speak. Furthermore, boldness, the opposite of shyness, may cause its own problems, such as impertinence or inappropriate behavior.
# Origins
The initial causes of shyness vary. Scientists have located some genetic data that supports the hypothesis that shyness is at least partially genetic. However, there is also evidence that the environment in which a person is raised can affect their shyness. This includes child abuse, particularly emotional abuse such as ridicule. Shyness can originate after a person has experienced a physical anxiety reaction; at other times, shyness seems to develop first and then later causes physical symptoms of anxiety.
Shyness differs from social anxiety, which is a broader, often depression-related psychological condition including the experience of fear, apprehension or worry regarding social situations and being evaluated by others to panic-inducing extents.
# Genetics and heredity
The genetics of shyness is a relatively small area of research that has been receiving an even smaller amount of attention, although papers on the biological bases of shyness date back at least to 1988.
Some research has indicated that shyness and aggression are related—through long and short forms of the gene DRD4, though considerably more research on this is needed. Further, it has been suggested that shyness and social phobia (the distinction between the two is becoming ever more blurred) are related to obsessive-compulsive disorder.
As with other studies of behavioral genetics, the study of shyness is complicated by the number of genes involved in, and the confusion in defining, the phenotype. Naming the phenotype – and translation of terms between genetics and psychology — also causes problems. In some research, "behavioral inhibition" is studied, in others anxiety or social inhibition is. One solution to this problem is to study the genetics of underlying traits, such as "anxious temperament."
Several genetic links to shyness are current areas of research. One of the most promising is the serotonin transporter promoter region polymorphism (5-HTTLPR), the long form of which has been shown to be highly correlated with shyness in grade school children. Previous studies had shown a connection between this form of the gene and both obsessive-compulsive disorder and autism. Mouse models have also been used, to derive genes suitable for further study in humans; one such gene, the glutamic acid decarboxylase gene (which encodes an enzyme that functions in GABA synthesis), has so far been shown to have some association with behavioral inhibition. Another gene, the dopamine D4 receptor gene (DRD4) exon III polymorphism, had been the subject of studies in both shyness and aggression, and is currently the subject of studies on the "novelty seeking" trait. A 1996 study of anxiety-related traits (shyness being one of these) remarked that, "Although twin studies have indicated that individual variation in measures of anxiety-related personality traits is 40-60% heritable, none of the relevant genes has yet been identified," and that "10 to 15 genes might be predicted to be involved" in the anxiety trait. Progress has been made since then, especially in identifying other potential genes involved in personality traits, but there has been little progress made towards confirming these relationships. The long version of the 5-HTT gene-linked polymorphic region (5-HTTLPR) is now postulated to be correlated with shyness, but in the 1996 study, the short version was shown to be related to anxiety-based traits. This confusion and contradiction does not oppose the genetic basis of personality traits, but does emphasize the amount of research there is still to be done before the bases of even one or two of these characteristics can be identified.
# Environmental factors
Excessive shyness, embarrassment, self consciousness and timidity, social-phobia and lack of self-confidence are also components of erethism, which is a symptom complex that appears in cases of mercury poisoning[1][2]. | https://www.wikidoc.org/index.php/Shyness | |
1bbed2f7d43727d5411fa2409f827e99f1f35dec | wikidoc | Silicon | Silicon
Silicon (Template:PronEng or Template:IPA, Template:Lang-la) is the chemical element that has the symbol Si and atomic number 14. A tetravalent metalloid, silicon is less reactive than its chemical analog carbon. As the eighth most common element in the universe by mass, silicon occasionally occurs as the pure free element in nature, but is more widely distributed in dusts, planetoids and planets as various forms of silicon dioxide or silicate. On Earth, silicon is the second most abundant element (after oxygen) in the crust, making up 25.7% of the crust by mass.
Silicon has many industrial uses. Elemental silicon is the principal component of most semiconductor devices, most importantly integrated circuits or microchips. Silicon is widely used in semiconductors because it remains a semiconductor at higher temperatures than the semiconductor germanium and because its native oxide is easily grown in a furnace and forms a better semiconductor/dielectric interface than almost all other material combinations.
In the form of silica and silicates, silicon forms useful glasses, cements, and ceramics. It is also a component of silicones, a class-name for various synthetic plastic substances made of silicon, oxygen, carbon and hydrogen, often confused with silicon itself.
Silicon is an essential element in biology, although only tiny traces of it appear to be required by animals. It is much more important to the metabolism of plants, particularly many grasses, and silicic acid (a type of silica) forms the basis of the striking array of protective shells of the microscopic diatoms.
# Notable characteristics
The outer electron orbitals (half filled subshell holding up to eight electrons) have the same structure as in carbon and the two elements are very similar chemically. Even though it is a relatively inert element, silicon still reacts with halogens and dilute alkalis, but most acids (except for some hyper-reactive combinations of nitric acid and hydrofluoric acid) do not affect it. Having four bonding electrons however gives it, like carbon, many opportunities to combine with other elements or compounds under the right circumstances.
Both silicon and carbon are semiconductors, readily either donating or sharing their four outer electrons allowing many different forms of chemical bonding. Pure silicon has a negative temperature coefficient of resistance, since the number of free charge carriers increases with temperature. The electrical resistance of single crystal silicon significantly changes under the application of mechanical stress due to the piezoresistive effect.
In its crystalline form, pure silicon has a gray color and a metallic luster. It is similar to glass in that it is rather strong, very brittle, and prone to chipping.
# Occurrence
Measured by mass, silicon makes up 25.7% of the Earth's crust and is the second most abundant element on Earth, after oxygen. Pure silicon crystals are only occasionally found in nature; they can be found as inclusions with gold and in volcanic exhalations. Silicon is usually found in the form of silicon dioxide (also known as silica), and silicate.
Silica occurs in minerals consisting of (practically) pure silicon dioxide in different crystalline forms. Sand, amethyst, agate, quartz, rock crystal, chalcedony, flint, jasper, and opal are some of the forms in which silicon dioxide appears. (They are known as "lithogenic", as opposed to "biogenic", silicas.)
Silicon also occurs as silicates (various minerals containing silicon, oxygen and one or another metal), for example feldspar. These minerals occur in clay, sand and various types of rock such as granite and sandstone. Asbestos, feldspar, clay, hornblende, and mica are a few of the many silicate minerals.
Silicon is a principal component of aerolites, which are a class of meteoroids, and also is a component of tektites, which are a natural form of glass.
See also Category:Silicate minerals
# Isotopes
Silicon has numerous known isotopes, with mass numbers ranging from 22 to 44. 28Si (the most abundant isotope, at 92.23%), 29Si (4.67%), and 30Si (3.1%) are stable; 32Si is a radioactive isotope produced by argon decay. Its half-life has been determined to be approximately 170 years (0.21 MeV), and it decays by beta - emission to 32P (which has a 14.28 day half-life ) and then to 32S.
# Compounds
For examples of silicon compounds see silicate, silane (SiH4), silicic acid (H4SiO4), silicon carbide (SiC), silicon dioxide (SiO2), silicon tetrachloride (SiCl4), silicon tetrafluoride (SiF4), and trichlorosilane (HSiCl3).
See also Category:Silicon compounds
# Applications
As the second most abundant element in the earth's crust, silicon is vital to the construction industry as a principal constituent of natural stone, glass, concrete and cement. Silicon's greatest impact on the modern world's economy and lifestyle has resulted from its use as the substrate in the manufacture of discrete electronic devices such as power transistors, and in the development of integrated circuits such as computer chips.
## Alloys
- The largest application of pure silicon (metallurgical grade silicon) is in aluminium-silicon alloys, often called "light alloys", to produce cast parts, mainly for automotive industry. (This represents about 55% of the world consumption of pure silicon.)
- Steel and cast iron: Silicon is an important constituent of some steels, and it is used in the production process of cast iron. It is introduced as ferrosilicon or silicocalcium alloys.
## In electronic applications
- Pure silicon is also used to produce ultra-pure silicon for electronic and photovoltaic applications:
Semiconductor: Ultrapure silicon can be doped with other elements to adjust its electrical response by controlling the number and charge (positive or negative) of current carriers. Such control is necessary for transistors, solar cells, microprocessors, semiconductor detectors and other semiconductor devices which are used in electronics and other high-tech applications.
Photonics: Silicon can be used as a continuous wave Raman laser to produce coherent light. (Though it is ineffective as a light source.)
LCDs and solar cells: Hydrogenated amorphous silicon is widely used in the production of low-cost, large-area electronics in applications such as LCDs. It has also shown promise for large-area, low-cost thin-film solar cells.
- Semiconductor: Ultrapure silicon can be doped with other elements to adjust its electrical response by controlling the number and charge (positive or negative) of current carriers. Such control is necessary for transistors, solar cells, microprocessors, semiconductor detectors and other semiconductor devices which are used in electronics and other high-tech applications.
- Photonics: Silicon can be used as a continuous wave Raman laser to produce coherent light. (Though it is ineffective as a light source.)
- LCDs and solar cells: Hydrogenated amorphous silicon is widely used in the production of low-cost, large-area electronics in applications such as LCDs. It has also shown promise for large-area, low-cost thin-film solar cells.
## Silicones
The second largest application of silicon (about 40% of world consumption) is as a raw material in the production of silicones, compounds containing silicon-oxygen and silicon-carbon bonds that have the capability to acting as bonding intermediates between glass and organic compounds, and to form polymers with useful properties such as impermeability to water, flexibility and resistance to chemical attack. Silicones are used in waterproofing treatments, moulding compounds and mould-release agents, mechanical seals, high temperature greases and waxes, caulking compounds and even in applications as diverse as breast implants and explosives and pyrotechnics .
- Construction: Silicon dioxide or silica in the form of sand and clay is an important ingredient of concrete and brick and is also used to produce Portland cement.
- Pottery/Enamel is a refractory material used in high-temperature material production and its silicates are used in making enamels and pottery.
- Glass: Silica from sand is a principal component of glass. Glass can be made into a great variety of shapes and with many different physical properties. Silica is used as a base material to make window glass, containers, insulators, and many other useful objects.
- Abrasives: Silicon carbide is one of the most important abrasives.
- Silly Putty was originally made by adding boric acid to silicone oil. Now name-brand Silly Putty also contains significant amounts of elemental silicon. (Silicon binds to the silicone and allows the material to bounce 20% higher.)
See also Category:Silicon compounds
# Production
Silicon is commercially prepared by the reaction of high-purity silica with wood, charcoal, and coal, in an electric arc furnace using carbon electrodes. At temperatures over 1900 °C, the carbon reduces the silica to silicon according to the chemical equation
Liquid silicon collects in the bottom of the furnace, and is then drained and cooled. The silicon produced via this process is called metallurgical grade silicon and is at least 98% pure. Using this method, silicon carbide, SiC, can form. However, provided the amount of SiO2 is kept high, silicon carbide may be eliminated, as explained by this equation:
In 2005, metallurgical grade silicon cost about $ 0.77 per pound ($1.70/kg).
# Purification
The use of silicon in semiconductor devices demands a much greater purity than afforded by metallurgical grade silicon. Historically, a number of methods have been used to produce high-purity silicon.
## Physical methods
Early silicon purification techniques were based on the fact that if silicon is melted and re-solidified, the last parts of the mass to solidify contain most of the impurities. The earliest method of silicon purification, first described in 1919 and used on a limited basis to make radar components during World War II, involved crushing metallurgical grade silicon and then partially dissolving the silicon powder in an acid. When crushed, the silicon cracked so that the weaker impurity-rich regions were on the outside of the resulting grains of silicon. As a result, the impurity-rich silicon was the first to be dissolved when treated with acid, leaving behind a more pure product.
In zone melting, also called zone refining, the first silicon purification method to be widely used industrially, rods of metallurgical grade silicon are heated to melt at one end. Then, the heater is slowly moved down the length of the rod, keeping a small length of the rod molten as the silicon cools and re-solidifies behind it. Since most impurities tend to remain in the molten region rather than re-solidify, when the process is complete, most of the impurities in the rod will have been moved into the end that was the last to be melted. This end is then cut off and discarded, and the process repeated if a still higher purity is desired.
## Chemical methods
Today, silicon is purified by converting it to a silicon compound that can be more easily purified than in its original state, and then converting that silicon element back into pure silicon. Trichlorosilane is the silicon compound most commonly used as the intermediate, although silicon tetrachloride and silane are also used. When these gases are blown over silicon at high temperature, they decompose to high-purity silicon.
At one time, DuPont produced ultra-pure silicon by reacting silicon tetrachloride with high-purity zinc vapors at 950 °C, producing silicon according to the chemical equation
However, this technique was plagued with practical problems (such as the zinc chloride byproduct solidifying and clogging lines) and was eventually abandoned in favor of the Siemens process.
In the Siemens process, high-purity silicon rods are exposed to trichlorosilane at 1150 °C. The trichlorosilane gas decomposes and deposits additional silicon onto the rods, enlarging them according to chemical reactions like
Silicon produced from this and similar processes is called polycrystalline silicon. Polycrystalline silicon typically has impurity levels of less than 10−9.
In 2006 REC announced construction of a plant based on fluidized bed technology using silane .
# Crystallization
The majority of silicon crystals grown for device production are produced by the Czochralski process, (CZ-Si) since it is the cheapest method available and it is capable of producing large size crystals. However, silicon single-crystals grown by the Czochralski method contain impurities since the crucible which contains the melt dissolves. For certain electronic devices, particularly those required for high power applications, silicon grown by the Czochralski method is not pure enough. For these applications, float-zone silicon (FZ-Si) can be used instead. It is worth mentioning though, in contrast with CZ-Si method in which the seed is dipped into the silicon melt and the growing crystal is pulled upward, the thin seed crystal in the FZ-Si method sustains the growing crystal as well as the polysilicon rod from the bottom. As a result, it is difficult to grow large size crystals using the float-zone method. Today, all the dislocation-free silicon crystals used in semiconductor industry with diameter 300mm or larger are grown by the Czochralski method with purity level significantly improved.
# Different forms of silicon
- Granular silicon
Granular silicon
- Polycrystal silicon
Polycrystal silicon
- Silicon monocrystal
Silicon monocrystal
- Nanocrystalline silicon
Nanocrystalline silicon
- Silicon Ingot
Silicon Ingot
- Broken silicon ingot
Broken silicon ingot
One can notice the color change in silicon nanopowder. This is caused by the quantum effects which occur in particles of nanometric dimensions. See also Potential well, Quantum dot, and Nanoparticle.
# Silicon-based life
Since silicon is similar to carbon, particularly in its valency, some people have proposed the possibility of silicon-based life. One main detraction for silicon-based life is that unlike carbon, silicon does not have the tendency to form double and triple bonds.
Although there are no known forms of life that rely entirely on silicon-based chemistry, there are some that rely on silicon minerals for specific functions. Some bacteria and other forms of life, such as the protozoa radiolaria, have silicon dioxide skeletons, and the sea urchin has spines made of silicon dioxide. These forms of silicon dioxide are known as biogenic silica. Silicate bacteria use silicates in their metabolism.
Life as we know it could not have developed based on a silicon biochemistry. The main reason for this fact is that life on Earth depends on the carbon cycle: autotrophic entities use carbon dioxide to synthesize organic compounds with carbon, which is then used as food by heterotrophic entities, which produce energy and carbon dioxide from these compounds. If carbon was to be replaced with silicon, there would be a need for a silicon cycle. However, silicon dioxide precipitates in aqueous systems, and cannot be transported among living beings by common biological means.
As such, another solvent would be necessary to sustain silicon-based life forms; it would be difficult (if not impossible) to find another common compound with the unusual properties of water which make it an ideal solvent for carbon-based life. Larger silicon compounds analogous to common hydrocarbon chains (silanes) are also generally unstable owing to the larger atomic radius of silicon and the correspondingly weaker silicon-silicon bond; silanes decompose readily and often violently in the presence of oxygen making them unsuitable for an oxidizing atmosphere such as our own. Silicon also does not readily participate in pi-bonding (the second and third bonds in triple bonds and double bonds are pi-bonds) as its p-orbital electrons experience greater shielding and are less able to take on the necessary geometry. Furthermore, although some silicon rings (cyclosilanes) analogous to common the cycloalkanes formed by carbon have been synthesized, these are largely unknown. Their synthesis suffers from the difficulties inherent in producing any silane compound, whereas carbon will readily form five-, six-, and seven-membered rings by a variety of pathways (the Diels-Alder reaction is one naturally-occurring example), even in the presence of oxygen. Silicon's inability to readily form long silane chains, multiple bonds, and rings severely limits the diversity of compounds that can be synthesized from it. Under known conditions, silicon chemistry simply cannot begin to approach the diversity of organic chemistry, a crucial factor in carbon's role in biology.
However, silicon-based life could be construed as being life which exists under a computational substrate. This concept is yet to be explored in mainstream technology but receives ample coverage by sci-fi authors.
A. G. Cairns-Smith has proposed that the first living organisms to exist were forms of clay minerals—which were probably based around the silicon atom.
# History
Silicon was first identified by Antoine Lavoisier in 1787 (as a component of the Latin Template:Wdy, or silicis (meaning what were more generally termed "the flints" or "Hard Rocks" during the Early Modern era where nowadays as we would say "silica" or "silicates"), and was later mistaken by Humphry Davy in 1800 for a compound. In 1811 Gay-Lussac and Thénard probably prepared impure amorphous silicon through the heating of potassium with silicon tetrafluoride. It was first discovered as an element by Berzelius in 1823. In 1824, Berzelius prepared amorphous silicon using approximately the same method as Lussac. Berzelius also purified the product by repeatedly washing it.
Because silicon is an important element in semiconductors and high-tech devices, the high-tech region of Silicon Valley, California is named after this element. | Silicon
Template:Infobox silicon
Silicon (Template:PronEng or Template:IPA, Template:Lang-la) is the chemical element that has the symbol Si and atomic number 14. A tetravalent metalloid, silicon is less reactive than its chemical analog carbon. As the eighth most common element in the universe by mass, silicon occasionally occurs as the pure free element in nature, but is more widely distributed in dusts, planetoids and planets as various forms of silicon dioxide or silicate. On Earth, silicon is the second most abundant element (after oxygen) in the crust, making up 25.7% of the crust by mass.
Silicon has many industrial uses. Elemental silicon is the principal component of most semiconductor devices, most importantly integrated circuits or microchips. Silicon is widely used in semiconductors because it remains a semiconductor at higher temperatures than the semiconductor germanium and because its native oxide is easily grown in a furnace and forms a better semiconductor/dielectric interface than almost all other material combinations.
In the form of silica and silicates, silicon forms useful glasses, cements, and ceramics. It is also a component of silicones, a class-name for various synthetic plastic substances made of silicon, oxygen, carbon and hydrogen, often confused with silicon itself.
Silicon is an essential element in biology, although only tiny traces of it appear to be required by animals. It is much more important to the metabolism of plants, particularly many grasses, and silicic acid (a type of silica) forms the basis of the striking array of protective shells of the microscopic diatoms.
# Notable characteristics
The outer electron orbitals (half filled subshell holding up to eight electrons) have the same structure as in carbon and the two elements are very similar chemically. Even though it is a relatively inert element, silicon still reacts with halogens and dilute alkalis, but most acids (except for some hyper-reactive combinations of nitric acid and hydrofluoric acid) do not affect it. Having four bonding electrons however gives it, like carbon, many opportunities to combine with other elements or compounds under the right circumstances.
Both silicon and carbon are semiconductors, readily either donating or sharing their four outer electrons allowing many different forms of chemical bonding. Pure silicon has a negative temperature coefficient of resistance, since the number of free charge carriers increases with temperature. The electrical resistance of single crystal silicon significantly changes under the application of mechanical stress due to the piezoresistive effect.
In its crystalline form, pure silicon has a gray color and a metallic luster. It is similar to glass in that it is rather strong, very brittle, and prone to chipping.
# Occurrence
Measured by mass, silicon makes up 25.7% of the Earth's crust and is the second most abundant element on Earth, after oxygen. Pure silicon crystals are only occasionally found in nature; they can be found as inclusions with gold and in volcanic exhalations. Silicon is usually found in the form of silicon dioxide (also known as silica), and silicate.
Silica occurs in minerals consisting of (practically) pure silicon dioxide in different crystalline forms. Sand, amethyst, agate, quartz, rock crystal, chalcedony, flint, jasper, and opal are some of the forms in which silicon dioxide appears. (They are known as "lithogenic", as opposed to "biogenic", silicas.)
Silicon also occurs as silicates (various minerals containing silicon, oxygen and one or another metal), for example feldspar. These minerals occur in clay, sand and various types of rock such as granite and sandstone. Asbestos, feldspar, clay, hornblende, and mica are a few of the many silicate minerals.
Silicon is a principal component of aerolites, which are a class of meteoroids, and also is a component of tektites, which are a natural form of glass.
See also Category:Silicate minerals
# Isotopes
Silicon has numerous known isotopes, with mass numbers ranging from 22 to 44. 28Si (the most abundant isotope, at 92.23%), 29Si (4.67%), and 30Si (3.1%) are stable; 32Si is a radioactive isotope produced by argon decay. Its half-life has been determined to be approximately 170 years (0.21 MeV), and it decays by beta - emission to 32P (which has a 14.28 day half-life [2]) and then to 32S.
# Compounds
Template:Expand-section
For examples of silicon compounds see silicate, silane (SiH4), silicic acid (H4SiO4), silicon carbide (SiC), silicon dioxide (SiO2), silicon tetrachloride (SiCl4), silicon tetrafluoride (SiF4), and trichlorosilane (HSiCl3).
See also Category:Silicon compounds
# Applications
As the second most abundant element in the earth's crust, silicon is vital to the construction industry as a principal constituent of natural stone, glass, concrete and cement. Silicon's greatest impact on the modern world's economy and lifestyle has resulted from its use as the substrate in the manufacture of discrete electronic devices such as power transistors, and in the development of integrated circuits such as computer chips.
## Alloys
- The largest application of pure silicon (metallurgical grade silicon) is in aluminium-silicon alloys, often called "light alloys", to produce cast parts, mainly for automotive industry. (This represents about 55% of the world consumption of pure silicon.)
- Steel and cast iron: Silicon is an important constituent of some steels, and it is used in the production process of cast iron. It is introduced as ferrosilicon or silicocalcium alloys.
## In electronic applications
- Pure silicon is also used to produce ultra-pure silicon for electronic and photovoltaic applications:
Semiconductor: Ultrapure silicon can be doped with other elements to adjust its electrical response by controlling the number and charge (positive or negative) of current carriers. Such control is necessary for transistors, solar cells, microprocessors, semiconductor detectors and other semiconductor devices which are used in electronics and other high-tech applications.
Photonics: Silicon can be used as a continuous wave Raman laser to produce coherent light. (Though it is ineffective as a light source.)
LCDs and solar cells: Hydrogenated amorphous silicon is widely used in the production of low-cost, large-area electronics in applications such as LCDs. It has also shown promise for large-area, low-cost thin-film solar cells.
- Semiconductor: Ultrapure silicon can be doped with other elements to adjust its electrical response by controlling the number and charge (positive or negative) of current carriers. Such control is necessary for transistors, solar cells, microprocessors, semiconductor detectors and other semiconductor devices which are used in electronics and other high-tech applications.
- Photonics: Silicon can be used as a continuous wave Raman laser to produce coherent light. (Though it is ineffective as a light source.)
- LCDs and solar cells: Hydrogenated amorphous silicon is widely used in the production of low-cost, large-area electronics in applications such as LCDs. It has also shown promise for large-area, low-cost thin-film solar cells.
## Silicones
The second largest application of silicon (about 40% of world consumption) is as a raw material in the production of silicones, compounds containing silicon-oxygen and silicon-carbon bonds that have the capability to acting as bonding intermediates between glass and organic compounds, and to form polymers with useful properties such as impermeability to water, flexibility and resistance to chemical attack. Silicones are used in waterproofing treatments, moulding compounds and mould-release agents, mechanical seals, high temperature greases and waxes, caulking compounds and even in applications as diverse as breast implants and explosives and pyrotechnics [1] .
- Construction: Silicon dioxide or silica in the form of sand and clay is an important ingredient of concrete and brick and is also used to produce Portland cement.
- Pottery/Enamel is a refractory material used in high-temperature material production and its silicates are used in making enamels and pottery.
- Glass: Silica from sand is a principal component of glass. Glass can be made into a great variety of shapes and with many different physical properties. Silica is used as a base material to make window glass, containers, insulators, and many other useful objects.
- Abrasives: Silicon carbide is one of the most important abrasives.
- Silly Putty was originally made by adding boric acid to silicone oil. Now name-brand Silly Putty also contains significant amounts of elemental silicon. (Silicon binds to the silicone and allows the material to bounce 20% higher.)[citation needed]
See also Category:Silicon compounds
# Production
Silicon is commercially prepared by the reaction of high-purity silica with wood, charcoal, and coal, in an electric arc furnace using carbon electrodes. At temperatures over 1900 °C, the carbon reduces the silica to silicon according to the chemical equation
Liquid silicon collects in the bottom of the furnace, and is then drained and cooled. The silicon produced via this process is called metallurgical grade silicon and is at least 98% pure. Using this method, silicon carbide, SiC, can form. However, provided the amount of SiO2 is kept high, silicon carbide may be eliminated, as explained by this equation:
In 2005, metallurgical grade silicon cost about $ 0.77 per pound ($1.70/kg).[3]
# Purification
The use of silicon in semiconductor devices demands a much greater purity than afforded by metallurgical grade silicon. Historically, a number of methods have been used to produce high-purity silicon.
## Physical methods
Early silicon purification techniques were based on the fact that if silicon is melted and re-solidified, the last parts of the mass to solidify contain most of the impurities. The earliest method of silicon purification, first described in 1919 and used on a limited basis to make radar components during World War II, involved crushing metallurgical grade silicon and then partially dissolving the silicon powder in an acid. When crushed, the silicon cracked so that the weaker impurity-rich regions were on the outside of the resulting grains of silicon. As a result, the impurity-rich silicon was the first to be dissolved when treated with acid, leaving behind a more pure product.
In zone melting, also called zone refining, the first silicon purification method to be widely used industrially, rods of metallurgical grade silicon are heated to melt at one end. Then, the heater is slowly moved down the length of the rod, keeping a small length of the rod molten as the silicon cools and re-solidifies behind it. Since most impurities tend to remain in the molten region rather than re-solidify, when the process is complete, most of the impurities in the rod will have been moved into the end that was the last to be melted. This end is then cut off and discarded, and the process repeated if a still higher purity is desired.
## Chemical methods
Today, silicon is purified by converting it to a silicon compound that can be more easily purified than in its original state, and then converting that silicon element back into pure silicon. Trichlorosilane is the silicon compound most commonly used as the intermediate, although silicon tetrachloride and silane are also used. When these gases are blown over silicon at high temperature, they decompose to high-purity silicon.
At one time, DuPont produced ultra-pure silicon by reacting silicon tetrachloride with high-purity zinc vapors at 950 °C, producing silicon according to the chemical equation
However, this technique was plagued with practical problems (such as the zinc chloride byproduct solidifying and clogging lines) and was eventually abandoned in favor of the Siemens process.
In the Siemens process, high-purity silicon rods are exposed to trichlorosilane at 1150 °C. The trichlorosilane gas decomposes and deposits additional silicon onto the rods, enlarging them according to chemical reactions like
Silicon produced from this and similar processes is called polycrystalline silicon. Polycrystalline silicon typically has impurity levels of less than 10−9.
In 2006 REC announced construction of a plant based on fluidized bed technology using silane [2].
# Crystallization
The majority of silicon crystals grown for device production are produced by the Czochralski process, (CZ-Si) since it is the cheapest method available and it is capable of producing large size crystals. However, silicon single-crystals grown by the Czochralski method contain impurities since the crucible which contains the melt dissolves. For certain electronic devices, particularly those required for high power applications, silicon grown by the Czochralski method is not pure enough. For these applications, float-zone silicon (FZ-Si) can be used instead. It is worth mentioning though, in contrast with CZ-Si method in which the seed is dipped into the silicon melt and the growing crystal is pulled upward, the thin seed crystal in the FZ-Si method sustains the growing crystal as well as the polysilicon rod from the bottom. As a result, it is difficult to grow large size crystals using the float-zone method. Today, all the dislocation-free silicon crystals used in semiconductor industry with diameter 300mm or larger are grown by the Czochralski method with purity level significantly improved.
# Different forms of silicon
- Granular silicon
Granular silicon
- Polycrystal silicon
Polycrystal silicon
- Silicon monocrystal
Silicon monocrystal
- Nanocrystalline silicon
Nanocrystalline silicon
- Silicon Ingot
Silicon Ingot
- Broken silicon ingot
Broken silicon ingot
One can notice the color change in silicon nanopowder. This is caused by the quantum effects which occur in particles of nanometric dimensions. See also Potential well, Quantum dot, and Nanoparticle.
# Silicon-based life
Since silicon is similar to carbon, particularly in its valency, some people have proposed the possibility of silicon-based life. One main detraction for silicon-based life is that unlike carbon, silicon does not have the tendency to form double and triple bonds.
Although there are no known forms of life that rely entirely on silicon-based chemistry, there are some that rely on silicon minerals for specific functions. Some bacteria and other forms of life, such as the protozoa radiolaria, have silicon dioxide skeletons, and the sea urchin has spines made of silicon dioxide. These forms of silicon dioxide are known as biogenic silica. Silicate bacteria use silicates in their metabolism.
Life as we know it could not have developed based on a silicon biochemistry. The main reason for this fact is that life on Earth depends on the carbon cycle: autotrophic entities use carbon dioxide to synthesize organic compounds with carbon, which is then used as food by heterotrophic entities, which produce energy and carbon dioxide from these compounds. If carbon was to be replaced with silicon, there would be a need for a silicon cycle. However, silicon dioxide precipitates in aqueous systems, and cannot be transported among living beings by common biological means.
As such, another solvent would be necessary to sustain silicon-based life forms; it would be difficult (if not impossible) to find another common compound with the unusual properties of water which make it an ideal solvent for carbon-based life. Larger silicon compounds analogous to common hydrocarbon chains (silanes) are also generally unstable owing to the larger atomic radius of silicon and the correspondingly weaker silicon-silicon bond; silanes decompose readily and often violently in the presence of oxygen making them unsuitable for an oxidizing atmosphere such as our own. Silicon also does not readily participate in pi-bonding (the second and third bonds in triple bonds and double bonds are pi-bonds) as its p-orbital electrons experience greater shielding and are less able to take on the necessary geometry. Furthermore, although some silicon rings (cyclosilanes) analogous to common the cycloalkanes formed by carbon have been synthesized, these are largely unknown. Their synthesis suffers from the difficulties inherent in producing any silane compound, whereas carbon will readily form five-, six-, and seven-membered rings by a variety of pathways (the Diels-Alder reaction is one naturally-occurring example), even in the presence of oxygen. Silicon's inability to readily form long silane chains, multiple bonds, and rings severely limits the diversity of compounds that can be synthesized from it. Under known conditions, silicon chemistry simply cannot begin to approach the diversity of organic chemistry, a crucial factor in carbon's role in biology.
However, silicon-based life could be construed as being life which exists under a computational substrate. This concept is yet to be explored in mainstream technology but receives ample coverage by sci-fi authors.
A. G. Cairns-Smith has proposed that the first living organisms to exist were forms of clay minerals—which were probably based around the silicon atom.
# History
Silicon was first identified by Antoine Lavoisier in 1787 (as a component of the Latin Template:Wdy, or silicis (meaning what were more generally termed "the flints" or "Hard Rocks" during the Early Modern era where nowadays as we would say "silica" or "silicates"), and was later mistaken by Humphry Davy in 1800 for a compound. In 1811 Gay-Lussac and Thénard probably prepared impure amorphous silicon through the heating of potassium with silicon tetrafluoride. It was first discovered as an element by Berzelius in 1823. In 1824, Berzelius prepared amorphous silicon using approximately the same method as Lussac. Berzelius also purified the product by repeatedly washing it.
Because silicon is an important element in semiconductors and high-tech devices, the high-tech region of Silicon Valley, California is named after this element. | https://www.wikidoc.org/index.php/Silicon | |
6590978a7ebfdd9d35ef2202a378bc85349cb99f | wikidoc | Sirenia | Sirenia
Sirenia is an order of fully aquatic, herbivorous mammals that inhabit rivers, estuaries, coastal marine waters, swamps, and marine wetlands. The order evolved during the Eocene epoch, more than 50 million years ago. Sirenians, including manatees and the Dugong, have major aquatic adaptations: forelimbs have modified into arms used for steering, the tail has modified into a paddle used for propulsion, hind limbs (legs) are but two small remnant bones floating deep in the muscle. They appear fat, but are fusiform, hydrodynamic, and highly muscular. Their skulls are highly modified for taking breaths of air at the water's surface and dentition is greatly reduced. The skeletal bones of both the manatee and dugong are very dense which helps to neutralize the buoyancy of their blubber. The manatee appears to have an almost unlimited ability to produce new teeth as the anterior teeth wear down. They have only two teats, located under their forelimbs, similar to elephants. The elephant are thought as the closest living relative of the sirenians.
The three manatee species (family Trichechidae) and the Dugong (family Dugongidae) are endangered species. All four living species are vulnerable to extinction from habitat loss and other negative impacts related to human population growth and coastal development. Already the Steller's Sea Cow has been hunted into extinction by humans. Manatees and the Dugong are the only marine mammals classified as herbivores. Unlike the other marine mammals (dolphins, whales, seals, sea lions, sea otters, and walruses), sirenians eat primarily sea-grasses and other aquatic vegetation and have an extremely low metabolism and poor tolerance for especially cold water. Sirenians have been observed eating dead animals (sea gulls), but their diet is made up primarily of vegetation. Like dolphins and whales, manatees and the Dugong are totally aquatic mammals that never leave the water — not even to give birth. These animals have been observed eating grass clippings from homes adjacent to water ways, but in this rare occurrence, only the top portion of the sirenia is lifted out of the water. The combination of these factors means that sirenians are restricted to warm shallow coastal waters, estuaries, and rivers, with healthy ecosystems that support large amounts of seagrass and/or other vegetation.
The Trichechidae species differ from Dugongidae in the shape of the skull and the shape of the tail.
- ORDER SIRENIA
Genus †Ishatherium
†Ishatherium subathuensis
Family †Prorastomidae
Genus †Pezosiren
†Pezosiren portelli
Genus †Prorastomus
†Prorastomus sirenoides
Family †Protosirenidae
Genus †Protosiren
†Protosiren minima
†Protosiren sattaensis
†Protosiren fraasi
†Protosiren smithae
Family Dugongidae
Genus †''Sirenotherium
†Sirenotherium pirabense
Subfamily Dugonginae
Genus Dugong
Dugong, Dugong dugon
Subfamily Hydrodamalinae
Genus †Dusisiren
†Dusisiren dewana
†Dusisiren jordani
†Dusisiren takasatensis
Genus †Hydrodamalis
†Hydrodamalis cuestae
Steller's Sea Cow, †Hydrodamalis gigas
Family Trichechidae
Genus Trichechus
West Indian Manatee, Trichechus manatus
Antillean Manatee, Trichechus manatus manatus
Florida Manatee, Trichechus manatus latirostris
African Manatee, Trichechus senegalensis
Amazonian Manatee, Trichechus inunguis
Dwarf Manatee, Trichechus bernhardi (validity questionable)
- Genus †Ishatherium
†Ishatherium subathuensis
- †Ishatherium subathuensis
- Family †Prorastomidae
Genus †Pezosiren
†Pezosiren portelli
Genus †Prorastomus
†Prorastomus sirenoides
- Genus †Pezosiren
†Pezosiren portelli
- †Pezosiren portelli
- Genus †Prorastomus
†Prorastomus sirenoides
- †Prorastomus sirenoides
- Family †Protosirenidae
Genus †Protosiren
†Protosiren minima
†Protosiren sattaensis
†Protosiren fraasi
†Protosiren smithae
- Genus †Protosiren
†Protosiren minima
†Protosiren sattaensis
†Protosiren fraasi
†Protosiren smithae
- †Protosiren minima
- †Protosiren sattaensis
- †Protosiren fraasi
- †Protosiren smithae
- Family Dugongidae
Genus †''Sirenotherium
†Sirenotherium pirabense
Subfamily Dugonginae
Genus Dugong
Dugong, Dugong dugon
Subfamily Hydrodamalinae
Genus †Dusisiren
†Dusisiren dewana
†Dusisiren jordani
†Dusisiren takasatensis
Genus †Hydrodamalis
†Hydrodamalis cuestae
Steller's Sea Cow, †Hydrodamalis gigas
- Genus †''Sirenotherium
†Sirenotherium pirabense
- †Sirenotherium pirabense
- Subfamily Dugonginae
Genus Dugong
Dugong, Dugong dugon
- Genus Dugong
Dugong, Dugong dugon
- Dugong, Dugong dugon
- Subfamily Hydrodamalinae
Genus †Dusisiren
†Dusisiren dewana
†Dusisiren jordani
†Dusisiren takasatensis
Genus †Hydrodamalis
†Hydrodamalis cuestae
Steller's Sea Cow, †Hydrodamalis gigas
- Genus †Dusisiren
†Dusisiren dewana
†Dusisiren jordani
†Dusisiren takasatensis
- †Dusisiren dewana
- †Dusisiren jordani
- †Dusisiren takasatensis
- Genus †Hydrodamalis
†Hydrodamalis cuestae
Steller's Sea Cow, †Hydrodamalis gigas
- †Hydrodamalis cuestae
- Steller's Sea Cow, †Hydrodamalis gigas
- Family Trichechidae
Genus Trichechus
West Indian Manatee, Trichechus manatus
Antillean Manatee, Trichechus manatus manatus
Florida Manatee, Trichechus manatus latirostris
African Manatee, Trichechus senegalensis
Amazonian Manatee, Trichechus inunguis
Dwarf Manatee, Trichechus bernhardi (validity questionable)
- Genus Trichechus
West Indian Manatee, Trichechus manatus
Antillean Manatee, Trichechus manatus manatus
Florida Manatee, Trichechus manatus latirostris
African Manatee, Trichechus senegalensis
Amazonian Manatee, Trichechus inunguis
Dwarf Manatee, Trichechus bernhardi (validity questionable)
- West Indian Manatee, Trichechus manatus
Antillean Manatee, Trichechus manatus manatus
Florida Manatee, Trichechus manatus latirostris
- Antillean Manatee, Trichechus manatus manatus
- Florida Manatee, Trichechus manatus latirostris
- African Manatee, Trichechus senegalensis
- Amazonian Manatee, Trichechus inunguis
- Dwarf Manatee, Trichechus bernhardi (validity questionable)
† extinct | Sirenia
Sirenia is an order of fully aquatic, herbivorous mammals that inhabit rivers, estuaries, coastal marine waters, swamps, and marine wetlands. The order evolved during the Eocene epoch, more than 50 million years ago. Sirenians, including manatees and the Dugong, have major aquatic adaptations: forelimbs have modified into arms used for steering, the tail has modified into a paddle used for propulsion, hind limbs (legs) are but two small remnant bones floating deep in the muscle. They appear fat, but are fusiform, hydrodynamic, and highly muscular. Their skulls are highly modified for taking breaths of air at the water's surface and dentition is greatly reduced. The skeletal bones of both the manatee and dugong are very dense which helps to neutralize the buoyancy of their blubber. The manatee appears to have an almost unlimited ability to produce new teeth as the anterior teeth wear down. They have only two teats, located under their forelimbs, similar to elephants. The elephant are thought as the closest living relative of the sirenians.
The three manatee species (family Trichechidae) and the Dugong (family Dugongidae) are endangered species. All four living species are vulnerable to extinction from habitat loss and other negative impacts related to human population growth and coastal development. Already the Steller's Sea Cow has been hunted into extinction by humans. Manatees and the Dugong are the only marine mammals classified as herbivores. Unlike the other marine mammals (dolphins, whales, seals, sea lions, sea otters, and walruses), sirenians eat primarily sea-grasses and other aquatic vegetation and have an extremely low metabolism and poor tolerance for especially cold water. Sirenians have been observed eating dead animals (sea gulls), but their diet is made up primarily of vegetation. Like dolphins and whales, manatees and the Dugong are totally aquatic mammals that never leave the water — not even to give birth. These animals have been observed eating grass clippings from homes adjacent to water ways, but in this rare occurrence, only the top portion of the sirenia is lifted out of the water. The combination of these factors means that sirenians are restricted to warm shallow coastal waters, estuaries, and rivers, with healthy ecosystems that support large amounts of seagrass and/or other vegetation.
The Trichechidae species differ from Dugongidae in the shape of the skull and the shape of the tail.
- ORDER SIRENIA
Genus †Ishatherium
†Ishatherium subathuensis
Family †Prorastomidae
Genus †Pezosiren
†Pezosiren portelli
Genus †Prorastomus
†Prorastomus sirenoides
Family †Protosirenidae
Genus †Protosiren
†Protosiren minima
†Protosiren sattaensis
†Protosiren fraasi
†Protosiren smithae
Family Dugongidae
Genus †''Sirenotherium
†Sirenotherium pirabense
Subfamily Dugonginae
Genus Dugong
Dugong, Dugong dugon
Subfamily Hydrodamalinae
Genus †Dusisiren
†Dusisiren dewana
†Dusisiren jordani
†Dusisiren takasatensis
Genus †Hydrodamalis
†Hydrodamalis cuestae
Steller's Sea Cow, †Hydrodamalis gigas
Family Trichechidae
Genus Trichechus
West Indian Manatee, Trichechus manatus
Antillean Manatee, Trichechus manatus manatus
Florida Manatee, Trichechus manatus latirostris
African Manatee, Trichechus senegalensis
Amazonian Manatee, Trichechus inunguis
Dwarf Manatee, Trichechus bernhardi (validity questionable)
- Genus †Ishatherium
†Ishatherium subathuensis
- †Ishatherium subathuensis
- Family †Prorastomidae
Genus †Pezosiren
†Pezosiren portelli
Genus †Prorastomus
†Prorastomus sirenoides
- Genus †Pezosiren
†Pezosiren portelli
- †Pezosiren portelli
- Genus †Prorastomus
†Prorastomus sirenoides
- †Prorastomus sirenoides
- Family †Protosirenidae
Genus †Protosiren
†Protosiren minima
†Protosiren sattaensis
†Protosiren fraasi
†Protosiren smithae
- Genus †Protosiren
†Protosiren minima
†Protosiren sattaensis
†Protosiren fraasi
†Protosiren smithae
- †Protosiren minima
- †Protosiren sattaensis
- †Protosiren fraasi
- †Protosiren smithae
- Family Dugongidae
Genus †''Sirenotherium
†Sirenotherium pirabense
Subfamily Dugonginae
Genus Dugong
Dugong, Dugong dugon
Subfamily Hydrodamalinae
Genus †Dusisiren
†Dusisiren dewana
†Dusisiren jordani
†Dusisiren takasatensis
Genus †Hydrodamalis
†Hydrodamalis cuestae
Steller's Sea Cow, †Hydrodamalis gigas
- Genus †''Sirenotherium
†Sirenotherium pirabense
- †Sirenotherium pirabense
- Subfamily Dugonginae
Genus Dugong
Dugong, Dugong dugon
- Genus Dugong
Dugong, Dugong dugon
- Dugong, Dugong dugon
- Subfamily Hydrodamalinae
Genus †Dusisiren
†Dusisiren dewana
†Dusisiren jordani
†Dusisiren takasatensis
Genus †Hydrodamalis
†Hydrodamalis cuestae
Steller's Sea Cow, †Hydrodamalis gigas
- Genus †Dusisiren
†Dusisiren dewana
†Dusisiren jordani
†Dusisiren takasatensis
- †Dusisiren dewana
- †Dusisiren jordani
- †Dusisiren takasatensis
- Genus †Hydrodamalis
†Hydrodamalis cuestae
Steller's Sea Cow, †Hydrodamalis gigas
- †Hydrodamalis cuestae
- Steller's Sea Cow, †Hydrodamalis gigas
- Family Trichechidae
Genus Trichechus
West Indian Manatee, Trichechus manatus
Antillean Manatee, Trichechus manatus manatus
Florida Manatee, Trichechus manatus latirostris
African Manatee, Trichechus senegalensis
Amazonian Manatee, Trichechus inunguis
Dwarf Manatee, Trichechus bernhardi (validity questionable)
- Genus Trichechus
West Indian Manatee, Trichechus manatus
Antillean Manatee, Trichechus manatus manatus
Florida Manatee, Trichechus manatus latirostris
African Manatee, Trichechus senegalensis
Amazonian Manatee, Trichechus inunguis
Dwarf Manatee, Trichechus bernhardi (validity questionable)
- West Indian Manatee, Trichechus manatus
Antillean Manatee, Trichechus manatus manatus
Florida Manatee, Trichechus manatus latirostris
- Antillean Manatee, Trichechus manatus manatus
- Florida Manatee, Trichechus manatus latirostris
- African Manatee, Trichechus senegalensis
- Amazonian Manatee, Trichechus inunguis
- Dwarf Manatee, Trichechus bernhardi (validity questionable)
† extinct | https://www.wikidoc.org/index.php/Sirenia | |
e070e0f1b3e68dff535698293f35f9da109ef637 | wikidoc | Sirtuin | Sirtuin
# Overview
Sirtuin is a class of enzyme, specifically NAD-dependent histone deacetylases (class 3), found in both prokaryotes and eukaryotes. They have been known to affect cellular metabolism through selective gene expression in eukaryotes (plants and animals). The name comes from silent mating type information regulation two, the gene responsible for cellular regulation in yeast.
# Sirtuins in organisms
## Sirtuins in lower eukaryotes
In yeast, roundworms, and fruitflies, sir2 is the name of the sirtuin-type enzyme. This research started in 1991 by Leonard Guarente of Harvard Medical School .
## Sirtuins as possible agents in retardation of the aging process
Sirtuins may be able to control age-related disorders in various organisms and in humans. These disorders include the aging process, obesity, metabolic syndrome, type II diabetes mellitus and Parkinson's disease. Normally, sirtuin activity is inhibited by nicotinamide, a component of vitamin B3 (also known as niacin), by binding to a specific receptor site. Drugs that interfere with this binding should increase sirtuin activity. It is known that resveratrol, found in red wine, can inhibit this interaction and is a putative agent for slowing down the aging process. However, the amount of resveratrol found naturally in red wine is too low to activate sirtuin, so potential therapeutic use would mandate purification and development of a therapeutic agent. Development of new agents that would specifically block the nicotinamide-binding site could provide an avenue to develop newer agents to treat degenerative diseases such as diabetes, atherosclerosis and gout.
# Sirtuins types
Sirtuins are classed according to their sequence of amino acids. Prokaryotics are in class U. In yeast (a lower eukaryote), sirtuin was initially found and named sir2. In more complex mammals there are seven known enzymes which act as on cellular regulation as sir2 does in yeast. These genes are designated as belonging to different classes, depending on their amino acid sequence structure.
Sirtuin list based on North/Verdin diagram.
# Companies associated with the sirtuin enzymes
## Elixir Pharmaceuticals
Founded by Leonard Guarente of Harvard Medical School, with Cynthia Kenyon of the University of California at San Francisco, with the intentions of treating aging through drugs which affect metabolism.
## Sirtris
Sirtris was co-founded by David Sinclair of the Harvard Medical School, and Dr. Christoph Westphal is the CEO. Sirtris is associated with the World Transhumanist Association. | Sirtuin
# Overview
Sirtuin is a class of enzyme, specifically NAD-dependent histone deacetylases (class 3), found in both prokaryotes and eukaryotes. They have been known to affect cellular metabolism through selective gene expression in eukaryotes (plants and animals). The name comes from silent mating type information regulation two[1], the gene responsible for cellular regulation in yeast.
# Sirtuins in organisms
## Sirtuins in lower eukaryotes
In yeast, roundworms, and fruitflies[2], sir2 is the name of the sirtuin-type enzyme. This research started in 1991 by Leonard Guarente of Harvard Medical School [3][4].
## Sirtuins as possible agents in retardation of the aging process
Sirtuins may be able to control age-related disorders in various organisms and in humans. These disorders include the aging process, obesity, metabolic syndrome, type II diabetes mellitus and Parkinson's disease. Normally, sirtuin activity is inhibited by nicotinamide, a component of vitamin B3 (also known as niacin), by binding to a specific receptor site. Drugs that interfere with this binding should increase sirtuin activity. It is known that resveratrol, found in red wine, can inhibit this interaction and is a putative agent for slowing down the aging process. However, the amount of resveratrol found naturally in red wine is too low to activate sirtuin, so potential therapeutic use would mandate purification and development of a therapeutic agent. Development of new agents that would specifically block the nicotinamide-binding site could provide an avenue to develop newer agents to treat degenerative diseases such as diabetes, atherosclerosis and gout.
# Sirtuins types
Sirtuins are classed according to their sequence of amino acids. Prokaryotics are in class U. In yeast (a lower eukaryote), sirtuin was initially found and named sir2. In more complex mammals there are seven known enzymes which act as on cellular regulation as sir2 does in yeast. These genes are designated as belonging to different classes, depending on their amino acid sequence structure.[5][6]
Sirtuin list based on North/Verdin diagram.[9]
# Companies associated with the sirtuin enzymes
## Elixir Pharmaceuticals
Founded by Leonard Guarente of Harvard Medical School, with Cynthia Kenyon of the University of California at San Francisco, with the intentions of treating aging through drugs which affect metabolism.[10]
## Sirtris
Sirtris[11] was co-founded by David Sinclair[12] of the Harvard Medical School, and Dr. Christoph Westphal is the CEO. Sirtris is associated with the World Transhumanist Association.[13] | https://www.wikidoc.org/index.php/Sirtuin | |
94ac78599b225c1402963d681cc662863638d08d | wikidoc | Sitting | Sitting
Sitting is a rest position supported by the buttocks or thighs where the torso is more or less upright. There are several ways for humans to sit.
# Types of sitting
## Sitting on the floor
The most common way of sitting on the floor involves bending the knees. One can also sit with the legs unbent, using something solid as support for the back or leaning on one's arms.
Sitting with bent legs can be done along two major lines; one with the legs mostly parallel and one where they cross each other. The parallel position is reminiscent of, and is sometimes used for, kneeling. The latter is a common pose for meditating.
### Parallel legs
- Seiza (正座, literally "correct sitting") is a Japanese word which describes the traditional formal way of sitting in that country. Sitting in seiza is kneeling on one's own lower legs, with the feet under the buttocks, toes pointed backwards. To sit in seiza for any length of time requires careful positioning of the heels under the sit bones of the hip, to minimize circulation loss.
- Squatting involves resting one's weight on the feet and usually also the buttocks and the backs of the thighs. Squatting is sometimes considered a form of standing, because the weight of the body is supported by the feet rather than the buttocks; however, a full squat resting the buttocks on the backs of the ankles relieves the muscles of the legs. Squatting (including the use of the squat toilet) is more common in Asian cultures.
### Cross-legged
- The position known as Indian or tailor style involves both feet bent inwards and under the body, crossing each other at the ankle.
- The lotus position involves resting each foot on the opposite thigh so that the soles face upwards. If only one foot is brought into this position, it is called a half-lotus position. This position is common in yoga and meditation.
- The Burmese position, named so because of its use in Buddhist sculptures in Burma, places both feet in front of the pelvis with knees bent and touching the floor to the sides. The heels are pointing toward pelvis or upward, and toes are pointed so that the tops of the feet lay on the ground. This looks similar to the cross legged position, but the feet are not placed underneath the thigh of the next leg, therefore the legs do not cross. Instead, one foot is placed in front of the other. This is a popular sitting alternative for those less comfortable with the use of the Lotus or half Lotus positions in meditation and yoga.
Zazen, the Japanese word for "sitting meditation", is a form of meditation rather than a particular posture. During zazen, practitioners may assume a lotus, half-lotus, Burmese, or seiza position.
## Sitting on a raised seat
Most raised surfaces at the appropriate height can be used as seats for humans, whether they are made for the purpose, such as chairs, stools and benches, or not. While the buttocks are nearly always rested on the raised surface, there are many differences in how one can hold one's legs and back.
There are two major styles of sitting on a raised surface. The first has one or two of the legs in front of the sitting person; in the second, sitting astride something, the legs incline outwards on either side of the body.
The feet can rest on the floor, or on a footrest, which can keep them vertical, horizontal, or at an angle in between. They can also dangle if the seat is sufficiently high. Legs can be kept right to the front of the body, spread apart, or one crossed over the other.
The upper body can be held upright, recline to either side or backwards, or one can lean forward.
## Posture
For years, children have been taught to "sit up straight" in their chairs. It was believed that a straight back (at 90 degrees with the legs) was the best posture, but recent studies show that sitting upright for hours causes increased stress on the back, and may be a cause of chronic back problems.
Researchers have found that a "135-degree back-thigh sitting posture" was the best posture to avoid back problems—that is, leaning back in the chair 45 degrees. Researchers found that the 90-degree position contributed most to strain on the spine, while the 135-degree position was the most relaxed.
The research does not, however, propose that slouching forward is a good alternative to sitting upright.
## Variations
Variations of the above, such as an aside variant with the legs resting above and beside the armrests (example), or the anti-authoritarian posture of reversing the chair and one's legs in front of the back of the chair.
# Kneeling chairs
Kneeling chairs (often just referred to as "ergonomic chairs"), encourage better posture than conventional chairs and they look quite different. To sit in a kneeling chair one rests one's buttocks on the upper sloping pad and rests the front of the lower legs atop the lower pad, i.e., the human position as both sitting and kneeling at the same time.
Kneeling chairs should not, in fact, be called "ergonomic" chairs because they go against what ergonomists recommend as a sitting position which reduces the risk of musculoskeletal injuries. Since the body is one long kinetic chain, prolonged sitting can lead to musculoskeletal injuries in any joint. "Neutral" sitting postures—postures that reduce the demands on the body—involve sitting fully back in a chair's seat pan and using the back rest for support. It is impossible for humans to sit unsupported for long periods of time and maintain neutral postures, nor is it advisable to try. Avoid using kneeling chairs as well as exercise balls for prolonged sitting.
# In mythology
In various mythologies and folk magic, sitting is a magical act that connects the person who sits, with other persons, states or places where he/she sat. | Sitting
Template:Otheruses4
Sitting is a rest position supported by the buttocks or thighs where the torso is more or less upright. There are several ways for humans to sit.
# Types of sitting
## Sitting on the floor
The most common way of sitting on the floor involves bending the knees. One can also sit with the legs unbent, using something solid as support for the back or leaning on one's arms.
Sitting with bent legs can be done along two major lines; one with the legs mostly parallel and one where they cross each other. The parallel position is reminiscent of, and is sometimes used for, kneeling. The latter is a common pose for meditating.
### Parallel legs
- Seiza (正座, literally "correct sitting") is a Japanese word which describes the traditional formal way of sitting in that country. Sitting in seiza is kneeling on one's own lower legs, with the feet under the buttocks, toes pointed backwards. To sit in seiza for any length of time requires careful positioning of the heels under the sit bones of the hip, to minimize circulation loss.
- Squatting involves resting one's weight on the feet and usually also the buttocks and the backs of the thighs. Squatting is sometimes considered a form of standing, because the weight of the body is supported by the feet rather than the buttocks; however, a full squat resting the buttocks on the backs of the ankles relieves the muscles of the legs. Squatting (including the use of the squat toilet) is more common in Asian cultures.[1]
### Cross-legged
- The position known as Indian or tailor style involves both feet bent inwards and under the body, crossing each other at the ankle.
- The lotus position involves resting each foot on the opposite thigh so that the soles face upwards. If only one foot is brought into this position, it is called a half-lotus position. This position is common in yoga and meditation.
- The Burmese position, named so because of its use in Buddhist sculptures in Burma, places both feet in front of the pelvis with knees bent and touching the floor to the sides. The heels are pointing toward pelvis or upward, and toes are pointed so that the tops of the feet lay on the ground. This looks similar to the cross legged position, but the feet are not placed underneath the thigh of the next leg, therefore the legs do not cross. Instead, one foot is placed in front of the other. This is a popular sitting alternative for those less comfortable with the use of the Lotus or half Lotus positions in meditation and yoga.
Zazen, the Japanese word for "sitting meditation", is a form of meditation rather than a particular posture. During zazen, practitioners may assume a lotus, half-lotus, Burmese, or seiza position.
## Sitting on a raised seat
Most raised surfaces at the appropriate height can be used as seats for humans, whether they are made for the purpose, such as chairs, stools and benches, or not. While the buttocks are nearly always rested on the raised surface, there are many differences in how one can hold one's legs and back.
There are two major styles of sitting on a raised surface. The first has one or two of the legs in front of the sitting person; in the second, sitting astride something, the legs incline outwards on either side of the body.
The feet can rest on the floor, or on a footrest, which can keep them vertical, horizontal, or at an angle in between. They can also dangle if the seat is sufficiently high. Legs can be kept right to the front of the body, spread apart, or one crossed over the other.
The upper body can be held upright, recline to either side or backwards, or one can lean forward.
## Posture
For years, children have been taught to "sit up straight" in their chairs. It was believed that a straight back (at 90 degrees with the legs) was the best posture, but recent studies show that sitting upright for hours causes increased stress on the back, and may be a cause of chronic back problems.
Researchers have found that a "135-degree back-thigh sitting posture" was the best posture to avoid back problems—that is, leaning back in the chair 45 degrees. Researchers found that the 90-degree position contributed most to strain on the spine, while the 135-degree position was the most relaxed.[2]
The research does not, however, propose that slouching forward is a good alternative to sitting upright.
## Variations
Variations of the above, such as an aside variant with the legs resting above and beside the armrests (example), or the anti-authoritarian posture of reversing the chair and one's legs in front of the back of the chair.
# Kneeling chairs
Kneeling chairs (often just referred to as "ergonomic chairs"), encourage better posture than conventional chairs and they look quite different. To sit in a kneeling chair one rests one's buttocks on the upper sloping pad and rests the front of the lower legs atop the lower pad, i.e., the human position as both sitting and kneeling at the same time.
Kneeling chairs should not, in fact, be called "ergonomic" chairs because they go against what ergonomists recommend as a sitting position which reduces the risk of musculoskeletal injuries. Since the body is one long kinetic chain, prolonged sitting can lead to musculoskeletal injuries in any joint. "Neutral" sitting postures—postures that reduce the demands on the body—involve sitting fully back in a chair's seat pan and using the back rest for support. It is impossible for humans to sit unsupported for long periods of time and maintain neutral postures, nor is it advisable to try. Avoid using kneeling chairs as well as exercise balls for prolonged sitting.
# In mythology
In various mythologies and folk magic, sitting is a magical act that connects the person who sits, with other persons, states or places where he/she sat.[1] | https://www.wikidoc.org/index.php/Sitting | |
303e5d14d79085fb6d45553909520d8b6fa251b6 | wikidoc | Skatole | Skatole
Skatole or 3-methylindole is a mildly toxic white crystalline organic compound belonging to the indole family. It occurs naturally in feces (it is produced from tryptophan in the mammalian digestive tract), beets, and coal tar, and has a strong fecal odor. In low concentrations it has a flowery smell and is found in several flowers and essential oils, including those of orange blossoms, jasmine, and Ziziphus mauritiana. It is used as a fragrance and fixative in many perfumes and as an aroma compound. Its name is derived from the Greek root skato- meaning "dung".
Skatole has been shown to cause pulmonary edema in goats, sheep, rats, and some strains of mice. It appears to selectively target Clara cells, which are the major site of cytochrome P450 enzymes in the lungs. These enzymes convert skatole to a reactive intermediate, 3-methyleneindolenine, which damages cells by forming protein adducts.
Skatole can be found as a white crystalline or fine powder solid, and it browns upon aging. It is nitrogenous and one of the rings is a pyrrole. It is soluble in alcohol and benzene and it gives violet color in potassium ferrocyanide (K4Fe(CN)6·3H2O) and sulfuric acid (H2SO4). Skatole has a double ring system which displays aromaticity. It is continuous (all atoms in the ring are sp² hybridized), planar, and follows the 4n+2 rule because it has 10 π electrons. It can be synthesized through a Fischer indole synthesis which was developed by Emil Fischer.
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.
In a 1994 report released by five top cigarette companies, skatole was listed as one of the 599 additives to cigarettes.
It is a flavoring ingredient. | Skatole
Template:Chembox new
Skatole or 3-methylindole is a mildly toxic white crystalline organic compound belonging to the indole family. It occurs naturally in feces (it is produced from tryptophan in the mammalian digestive tract), beets, and coal tar, and has a strong fecal odor. In low concentrations it has a flowery smell and is found in several flowers and essential oils, including those of orange blossoms, jasmine, and Ziziphus mauritiana. It is used as a fragrance and fixative in many perfumes and as an aroma compound. Its name is derived from the Greek root skato- meaning "dung".
Skatole has been shown to cause pulmonary edema in goats, sheep, rats, and some strains of mice. It appears to selectively target Clara cells, which are the major site of cytochrome P450 enzymes in the lungs. These enzymes convert skatole to a reactive intermediate, 3-methyleneindolenine, which damages cells by forming protein adducts[1].
Skatole can be found as a white crystalline or fine powder solid, and it browns upon aging. It is nitrogenous and one of the rings is a pyrrole. It is soluble in alcohol and benzene and it gives violet color in potassium ferrocyanide (K4Fe(CN)6·3H2O) and sulfuric acid (H2SO4). Skatole has a double ring system which displays aromaticity. It is continuous (all atoms in the ring are sp² hybridized), planar, and follows the 4n+2 rule because it has 10 π electrons. It can be synthesized through a Fischer indole synthesis which was developed by Emil Fischer.
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.[2]
In a 1994 report released by five top cigarette companies, skatole was listed as one of the 599 additives to cigarettes.
[3]
It is a flavoring ingredient. | https://www.wikidoc.org/index.php/Skatole | |
90a4b17e14c984823970ab0f0df30345e166d1d2 | wikidoc | Soliton | Soliton
In mathematics and physics, a soliton is a self-reinforcing solitary wave (a wave packet or pulse) that maintains its shape while it travels at constant speed; solitons are caused by a cancellation of nonlinear and dispersive effects in the medium. ("Dispersive effects" refer to dispersion relations, relationships between the frequency and the speed of waves in the medium.) Solitons are found in many physical phenomena, as they arise as the solutions of a widespread class of weakly nonlinear dispersive partial differential equations describing physical systems. The soliton phenomenon was first described by John Scott Russell (1808–1882) who observed a solitary wave in the Union Canal (a canal in Scotland), reproduced the phenomenon in a wave tank, and named it the "Wave of Translation".
# Definition
A single definition of a soliton is difficult to procure. Drazin and Johnson (1989) ascribe 3 properties to solitons:
- They are of permanent form;
- They are localised within a region;
- They can interact with other solitons, and emerge from the collision unchanged, except for a phase shift.
More formal definitions exist, but they require substantial mathematics. On the other hand, some scientists use the term soliton for phenomena that do not quite have these three properties (for instance, the 'light bullets' of nonlinear optics are often called solitons despite losing energy during interaction).
# Explanation
To see how dispersion and non-linearity can interact to produce permanent and localized wave forms, consider a pulse of light traveling in glass. This pulse can be thought of as consisting of light of several different frequencies; since glass shows dispersion, these different frequencies will travel at different speeds and the shape of the pulse will therefore change over time. However, there is also the non-linear Kerr effect: the speed of light of a given frequency depends on the light's amplitude or strength. If the pulse has just the right shape, the Kerr effect will exactly cancel the effect of dispersion, and the pulse's shape won't change over time: a soliton. See soliton (optics) for a much more detailed description.
Many exactly solvable models have soliton solutions, including the Korteweg-de Vries equation, the nonlinear Schrödinger equation, the coupled nonlinear Schrödinger equation, and the sine-Gordon equation. The soliton solutions are typically obtained by means of the inverse scattering transform and owe their stability to the integrability of the field equations. The mathematical theory of these equations is a broad and very active field of mathematical research.
Some types of tidal bore, a wave phenomenon of a few rivers including the River Severn, are 'undular': a wavefront followed by a train of solitons. Other solitons occur as the undersea internal waves, initiated by seabed topography, that propagate on the oceanic pycnocline. Atmospheric solitons also exist, such as the Morning Glory Cloud of the Gulf of Carpentaria, where pressure solitons travelling in a temperature inversion layer produce vast linear roll clouds. The recent and not widely accepted soliton model in neuroscience proposes to explain the signal conduction within neurons as pressure solitons.
A topological soliton, or topological defect, is any solution of a set of partial differential equations that is stable against decay to the "trivial solution" due to topological constraints, rather than due to the integrability of the field equations. The constraint arises almost always because the differential equations must obey a set of boundary conditions, and the boundary has a non-trivial homotopy group, preserved by the differential equations. Thus, the solutions of the differential equations can be classified into homotopy classes. There is no continuous transformation that will map a solution in one homotopy class to another; thus the solutions are truly distinct, and maintain their integrity, even in the face of extremely powerful forces. Examples of topological solitons include the screw dislocation in a crystalline lattice, the Dirac string and the magnetic monopole in electromagnetism, the Skyrmion and the Wess-Zumino-Witten model in quantum field theory, and cosmic strings and domain walls in cosmology.
# History
In 1834, John Scott Russell describes his wave of translation. The discovery is described here in Russell's own words:
"I was observing the motion of a boat which was rapidly drawn along a narrow channel by a pair of horses, when the boat suddenly stopped - not so the mass of water in the channel which it had put in motion; it accumulated round the prow of the vessel in a state of violent agitation, then suddenly leaving it behind, rolled forward with great velocity, assuming the form of a large solitary elevation, a rounded, smooth and well-defined heap of water, which continued its course along the channel apparently without change of form or diminution of speed. I followed it on horseback, and overtook it still rolling on at a rate of some eight or nine miles an hour, preserving its original figure some thirty feet long and a foot to a foot and a half in height. Its height gradually diminished, and after a chase of one or two miles I lost it in the windings of the channel. Such, in the month of August 1834, was my first chance interview with that singular and beautiful phenomenon which I have called the Wave of Translation".
(Note: This passage has been repeated in many papers and books on soliton theory.)
(Note: "Translation" here means that there is real mass transport such that water can be transported from one end of the canal to the other end by this "Wave of Translation". Usually there is no real mass transport from one side to another side for ordinary waves.)
Russell spent some time making practical and theoretical investigations of these waves, he built wave tanks at his home and noticed some key properties:
- The waves are stable, and can travel over very large distances (normal waves would tend to either flatten out, or steepen and topple over)
- The speed depends on the size of the wave, and its width on the depth of water.
- Unlike normal waves they will never merge — so a small wave is overtaken by a large one, rather than the two combining.
- If a wave is too big for the depth of water, it splits into two, one big and one small.
Russell's experimental work seemed at contrast with the Isaac Newton and Daniel Bernoulli's theories of hydrodynamics. George Biddell Airy and George Gabriel Stokes had difficulty to accept Russell's experimental observations because Russell's observations could not be explained by linear water wave theory. His contemporaries spent some time attempting to extend the theory but it would take until 1895 before Diederik Korteweg and Gustav de Vries provided the theoretical explanation.
(Note: Lord Rayleigh published a paper in Philosophical Magazine in 1876 to support John Scott Russell's experimental observation with his mathematical theory. In his 1876 paper, Lord Rayleigh mentioned Russell's name and also admitted that the first theoretical treatment was by Joseph Valentin Boussinesq in 1871. Joseph Boussinesq mentioned Russell's name in his 1871 paper. Thus Russell's observations on solitons were accepted as true by some prominent scientists within his own life time of 1808-1882. Korteweg and de Vries did not mention John Scott Russell's name at all in their 1895 paper but they did quote Boussinesq's paper in 1871 and Lord Rayleigh's paper in 1876. The paper by Korteweg and de Vries in 1895 was not the first theoretical treatment of this subject but it was a very important milestone in the history of the development of soliton theory.)
In 1965 Norman Zabusky of Bell Labs and Martin Kruskal of Princeton University first demonstrated soliton behaviour in media subject to the Korteweg-de Vries equation (KdV equation) in a computational investigation using a finite difference approach.
In 1967, Gardner, Greene, Kruskal and Miura discovered an inverse scattering transform enabling analytical solution of the KdV equation. The work of Peter Lax on Lax pairs and the Lax equation has since extended this to solution of many related soliton-generating systems.
# Solitons in fiber optics
Much experimentation has been done using solitons in fiber optics applications. Solitons' inherent stability make long-distance transmission possible without the use of repeaters, and could potentially double transmission capacity as well.
In 1973, Akira Hasegawa of AT&T Bell Labs was the first to suggest that solitons could exist in optical fibers, due to a balance between self-phase modulation and anomalous dispersion. He also proposed the idea of a soliton-based transmission system to increase performance of optical telecommunications.
Solitons in a fiber optic system are described by the Manakov equations.
In 1987, P. Emplit, J.P. Hamaide, F. Reynaud, C. Froehly and A. Barthelemy, from the Universities of Brussels and Limoges, made the first experimental observation of the propagation of a dark soliton, in an optical fiber.
In 1988, Linn Mollenauer and his team transmitted soliton pulses over 4,000 kilometers using a phenomenon called the Raman effect, named for the Indian scientist Sir C. V. Raman who first described it in the 1920s, to provide optical gain in the fiber.
In 1991, a Bell Labs research team transmitted solitons error-free at 2.5 gigabits per second over more than 14,000 kilometers, using erbium optical fiber amplifiers (spliced-in segments of optical fiber containing the rare earth element erbium). Pump lasers, coupled to the optical amplifiers, activate the erbium, which energizes the light pulses.
In 1998, Thierry Georges and his team at France Télécom R&D Center, combining optical solitons of different wavelengths (wavelength division multiplexing), demonstrated a data transmission of 1 terabit per second (1,000,000,000,000 units of information per second).
For some reasons, it is possible to observe both positive and negative solitons in optic fibre. However, usually only positive solitons are observed for water wave.
# Solitons in magnets
In magnets also exist different type soliton and other nonlinear waves. These magnetic solitons are an exact solutions of classical nonlinear differential equations - magnetic equations, e.g. the Landau-Lifshitz equation, continuum Heisenberg model, Ishimori equation, Mikhailov-Yaremchuk equation, nonlinear Schrodinger equation and so on.
# Bions
The bound state of two solitons is known as a bion.
In field theory Bion usually refers to the solution of the Born-Infeld model. The name appears to have been coined by G.W.Gibbons in order to distinguish this solution from the conventional soliton, understood as a regular, finite-energy (and usually stable) solution of a differential equation describing some physical system. The word regular means a smooth solution carrying no sources at all. However, the solution of the Born-Infeld model still carries a source in the form of a Dirac-delta function at the origin. As a consequence it displays a singularity in this point (although the electric field is everywhere regular). In some physical contexts (for instance string theory) this feature can be important, which motivated the introduction of a special name for this class of solitons.
On the other hand, when gravity is added (i.e. when considering the coupling of the Born-Infeld model to General Relativity) the corresponding solution is called EBIon, where "E" stands for "Einstein". | Soliton
Template:Cleanup
In mathematics and physics, a soliton is a self-reinforcing solitary wave (a wave packet or pulse) that maintains its shape while it travels at constant speed; solitons are caused by a cancellation of nonlinear and dispersive effects in the medium. ("Dispersive effects" refer to dispersion relations, relationships between the frequency and the speed of waves in the medium.) Solitons are found in many physical phenomena, as they arise as the solutions of a widespread class of weakly nonlinear dispersive partial differential equations describing physical systems. The soliton phenomenon was first described by John Scott Russell (1808–1882) who observed a solitary wave in the Union Canal (a canal in Scotland), reproduced the phenomenon in a wave tank, and named it the "Wave of Translation".
# Definition
A single definition of a soliton is difficult to procure. Drazin and Johnson (1989) ascribe 3 properties to solitons:
- They are of permanent form;
- They are localised within a region;
- They can interact with other solitons, and emerge from the collision unchanged, except for a phase shift.
More formal definitions exist, but they require substantial mathematics. On the other hand, some scientists use the term soliton for phenomena that do not quite have these three properties (for instance, the 'light bullets' of nonlinear optics are often called solitons despite losing energy during interaction).
# Explanation
To see how dispersion and non-linearity can interact to produce permanent and localized wave forms, consider a pulse of light traveling in glass. This pulse can be thought of as consisting of light of several different frequencies; since glass shows dispersion, these different frequencies will travel at different speeds and the shape of the pulse will therefore change over time. However, there is also the non-linear Kerr effect: the speed of light of a given frequency depends on the light's amplitude or strength. If the pulse has just the right shape, the Kerr effect will exactly cancel the effect of dispersion, and the pulse's shape won't change over time: a soliton. See soliton (optics) for a much more detailed description.
Many exactly solvable models have soliton solutions, including the Korteweg-de Vries equation, the nonlinear Schrödinger equation, the coupled nonlinear Schrödinger equation, and the sine-Gordon equation. The soliton solutions are typically obtained by means of the inverse scattering transform and owe their stability to the integrability of the field equations. The mathematical theory of these equations is a broad and very active field of mathematical research.
Some types of tidal bore, a wave phenomenon of a few rivers including the River Severn, are 'undular': a wavefront followed by a train of solitons. Other solitons occur as the undersea internal waves, initiated by seabed topography, that propagate on the oceanic pycnocline. Atmospheric solitons also exist, such as the Morning Glory Cloud of the Gulf of Carpentaria, where pressure solitons travelling in a temperature inversion layer produce vast linear roll clouds. The recent and not widely accepted soliton model in neuroscience proposes to explain the signal conduction within neurons as pressure solitons.
A topological soliton, or topological defect, is any solution of a set of partial differential equations that is stable against decay to the "trivial solution" due to topological constraints, rather than due to the integrability of the field equations. The constraint arises almost always because the differential equations must obey a set of boundary conditions, and the boundary has a non-trivial homotopy group, preserved by the differential equations. Thus, the solutions of the differential equations can be classified into homotopy classes. There is no continuous transformation that will map a solution in one homotopy class to another; thus the solutions are truly distinct, and maintain their integrity, even in the face of extremely powerful forces. Examples of topological solitons include the screw dislocation in a crystalline lattice, the Dirac string and the magnetic monopole in electromagnetism, the Skyrmion and the Wess-Zumino-Witten model in quantum field theory, and cosmic strings and domain walls in cosmology.
# History
In 1834, John Scott Russell describes his wave of translation. The discovery is described here in Russell's own words:
"I was observing the motion of a boat which was rapidly drawn along a narrow channel by a pair of horses, when the boat suddenly stopped - not so the mass of water in the channel which it had put in motion; it accumulated round the prow of the vessel in a state of violent agitation, then suddenly leaving it behind, rolled forward with great velocity, assuming the form of a large solitary elevation, a rounded, smooth and well-defined heap of water, which continued its course along the channel apparently without change of form or diminution of speed. I followed it on horseback, and overtook it still rolling on at a rate of some eight or nine miles an hour, preserving its original figure some thirty feet long and a foot to a foot and a half in height. Its height gradually diminished, and after a chase of one or two miles I lost it in the windings of the channel. Such, in the month of August 1834, was my first chance interview with that singular and beautiful phenomenon which I have called the Wave of Translation".[1]
(Note: This passage has been repeated in many papers and books on soliton theory.)
(Note: "Translation" here means that there is real mass transport such that water can be transported from one end of the canal to the other end by this "Wave of Translation". Usually there is no real mass transport from one side to another side for ordinary waves.)
Russell spent some time making practical and theoretical investigations of these waves, he built wave tanks at his home and noticed some key properties:
- The waves are stable, and can travel over very large distances (normal waves would tend to either flatten out, or steepen and topple over)
- The speed depends on the size of the wave, and its width on the depth of water.
- Unlike normal waves they will never merge — so a small wave is overtaken by a large one, rather than the two combining.
- If a wave is too big for the depth of water, it splits into two, one big and one small.
Russell's experimental work seemed at contrast with the Isaac Newton and Daniel Bernoulli's theories of hydrodynamics. George Biddell Airy and George Gabriel Stokes had difficulty to accept Russell's experimental observations because Russell's observations could not be explained by linear water wave theory. His contemporaries spent some time attempting to extend the theory but it would take until 1895 before Diederik Korteweg and Gustav de Vries provided the theoretical explanation.[2]
(Note: Lord Rayleigh published a paper in Philosophical Magazine in 1876 to support John Scott Russell's experimental observation with his mathematical theory. In his 1876 paper, Lord Rayleigh mentioned Russell's name and also admitted that the first theoretical treatment was by Joseph Valentin Boussinesq in 1871. Joseph Boussinesq mentioned Russell's name in his 1871 paper. Thus Russell's observations on solitons were accepted as true by some prominent scientists within his own life time of 1808-1882. Korteweg and de Vries did not mention John Scott Russell's name at all in their 1895 paper but they did quote Boussinesq's paper in 1871 and Lord Rayleigh's paper in 1876. The paper by Korteweg and de Vries in 1895 was not the first theoretical treatment of this subject but it was a very important milestone in the history of the development of soliton theory.)
In 1965 Norman Zabusky of Bell Labs and Martin Kruskal of Princeton University first demonstrated soliton behaviour in media subject to the Korteweg-de Vries equation (KdV equation) in a computational investigation using a finite difference approach.
In 1967, Gardner, Greene, Kruskal and Miura discovered an inverse scattering transform enabling analytical solution of the KdV equation. The work of Peter Lax on Lax pairs and the Lax equation has since extended this to solution of many related soliton-generating systems.
# Solitons in fiber optics
Much experimentation has been done using solitons in fiber optics applications. Solitons' inherent stability make long-distance transmission possible without the use of repeaters, and could potentially double transmission capacity as well.[3]
In 1973, Akira Hasegawa of AT&T Bell Labs was the first to suggest that solitons could exist in optical fibers, due to a balance between self-phase modulation and anomalous dispersion. He also proposed the idea of a soliton-based transmission system to increase performance of optical telecommunications.
Solitons in a fiber optic system are described by the Manakov equations.
In 1987, P. Emplit, J.P. Hamaide, F. Reynaud, C. Froehly and A. Barthelemy, from the Universities of Brussels and Limoges, made the first experimental observation of the propagation of a dark soliton, in an optical fiber.
In 1988, Linn Mollenauer and his team transmitted soliton pulses over 4,000 kilometers using a phenomenon called the Raman effect, named for the Indian scientist Sir C. V. Raman who first described it in the 1920s, to provide optical gain in the fiber.
In 1991, a Bell Labs research team transmitted solitons error-free at 2.5 gigabits per second over more than 14,000 kilometers, using erbium optical fiber amplifiers (spliced-in segments of optical fiber containing the rare earth element erbium). Pump lasers, coupled to the optical amplifiers, activate the erbium, which energizes the light pulses.
In 1998, Thierry Georges and his team at France Télécom R&D Center, combining optical solitons of different wavelengths (wavelength division multiplexing), demonstrated a data transmission of 1 terabit per second (1,000,000,000,000 units of information per second).
For some reasons, it is possible to observe both positive and negative solitons in optic fibre. However, usually only positive solitons are observed for water wave.
# Solitons in magnets
In magnets also exist different type soliton and other nonlinear waves. These magnetic solitons are an exact solutions of classical nonlinear differential equations - magnetic equations, e.g. the Landau-Lifshitz equation, continuum Heisenberg model, Ishimori equation, Mikhailov-Yaremchuk equation, nonlinear Schrodinger equation and so on.
# Bions
Template:Expand-section
The bound state of two solitons is known as a bion.
In field theory Bion usually refers to the solution of the Born-Infeld model. The name appears to have been coined by G.W.Gibbons in order to distinguish this solution from the conventional soliton, understood as a regular, finite-energy (and usually stable) solution of a differential equation describing some physical system. The word regular means a smooth solution carrying no sources at all. However, the solution of the Born-Infeld model still carries a source in the form of a Dirac-delta function at the origin. As a consequence it displays a singularity in this point (although the electric field is everywhere regular). In some physical contexts (for instance string theory) this feature can be important, which motivated the introduction of a special name for this class of solitons.
On the other hand, when gravity is added (i.e. when considering the coupling of the Born-Infeld model to General Relativity) the corresponding solution is called EBIon, where "E" stands for "Einstein". | https://www.wikidoc.org/index.php/Soliton | |
7f716be9346fbbc157573e955001cd9a16bafb80 | wikidoc | Somatic | Somatic
The term somatic refers to the body, as distinct from some other entity, such as the mind. The word comes from the Greek word Σωματικóς (Somatikòs), meaning "of the body". It has different meanings in various disciplines.
In neurobiology, somatic can be an adjective referring to the soma, the part of the neuron containing the cell nucleus.
In anatomy, somatic can refer to the part of the nervous system that controls voluntary movement and sensation and judges relative effort and weight, called proprioception. Additionally, somatic muscles are basically those of the musculo-skeletal system.
In genetics, somatic can refer to a cell or tissue that resides outside the germline (see somatic cell). For example, a somatic mutation cannot be transmitted to descendants in animals.
In the philosophy of education, certain ideas that have to do with the body and the mind have been called somatics. According to the originator of this usage of the term, "somatic awareness allows a person to glean wisdom from within". The usage of somatic as put forth by Thomas Hanna implies a truly integrated mind/body/spirit nature of humans. Thus far, the popular usage of this term has not fully realized this meaning, and a mind-body dualism still often occurs in disciplines describing themselves as somatic.
# Related terms
Soma is the whole axial portion of an animal, including the head, neck, trunk, and tail. | Somatic
The term somatic refers to the body, as distinct from some other entity, such as the mind. The word comes from the Greek word Σωματικóς (Somatikòs), meaning "of the body". It has different meanings in various disciplines.
In neurobiology, somatic can be an adjective referring to the soma, the part of the neuron containing the cell nucleus.
In anatomy, somatic can refer to the part of the nervous system that controls voluntary movement and sensation and judges relative effort and weight, called proprioception. Additionally, somatic muscles are basically those of the musculo-skeletal system.[1]
In genetics, somatic can refer to a cell or tissue that resides outside the germline (see somatic cell). For example, a somatic mutation cannot be transmitted to descendants in animals.
In the philosophy of education, certain ideas that have to do with the body and the mind have been called somatics. According to the originator of this usage of the term, "somatic awareness allows a person to glean wisdom from within".[2] The usage of somatic as put forth by Thomas Hanna implies a truly integrated mind/body/spirit nature of humans. Thus far, the popular usage of this term has not fully realized this meaning, and a mind-body dualism still often occurs in disciplines describing themselves as somatic.
# Related terms
Soma is the whole axial portion of an animal, including the head, neck, trunk, and tail.[1] | https://www.wikidoc.org/index.php/Somatic | |
94604f19c5ef607ea1214adc3d20f77ecabd43d6 | wikidoc | Sotalol | Sotalol
- Therapy with sotalol hydrochloride tablets (AF) must be initiated (and, if necessary, titrated) in a setting that provides continuous electrocardiographic (ECG) monitoring and in the presence of personnel trained in the management of serious ventricular arrhythmias. Patients should continue to be monitored in this way for a minimum of 3 days on the maintenance dose. In addition, patients should not be discharged within 12 hours of electrical or pharmacological conversion to normal sinus rhythm.
- The QT interval is used to determine patient eligibility for sotalol hydrochloride tablets (AF) treatment and for monitoring safety during treatment. The baseline QT interval must be ≤450 msec in order for a patient to be started on sotalol hydrochloride tablets (AF) therapy. During initiation and titration, the QT interval should be monitored 2 to 4 hours after each dose. If the QT interval prolongs to 500 msec or greater, the dose must be reduced or the drug discontinued.
- The dose of sotalol hydrochloride tablets, USP (AF) must be individualized according to calculated creatinine clearance. In patients with a creatinine clearance >60 mL/min sotalol hydrochloride tablets (AF) are administered twice daily (BID) while in those with a creatinine clearance between 40 and 60 mL/min, the dose is administered once daily (QD) or half the dose is administered twice daily (BID). In patients with a creatinine clearance less than 40 mL/min sotalol hydrochloride tablets (AF) are contraindicated. The recommended initial dose of sotalol hydrochloride tablets (AF) is 80 mg and is initiated as shown in the dosing algorithm described below. The 80 mg dose can be titrated upward to 100 mg or 120 mg during initial hospitalization or after discharge on 80 mg in the event of recurrence, by rehospitalization and repeating the same steps used during the initiation of therapy.
- Patients with atrial fibrillation should be anticoagulated according to usual medical practice. Hypokalemia should be corrected before initiation of sotalol hydrochloride tablets (AF) therapy.
- Patients to be discharged on sotalol hydrochloride tablets (AF) therapy from an in-patient setting should have an adequate supply of sotalol hydrochloride tablets (AF), to allow uninterrupted therapy until the patient can fill a sotalol hydrochloride tablets (AF) prescription.
- Step 1. Electrocardiographic assessment: Prior to administration of the first dose, the QT interval must be determined using an average of 5 beats. If the baseline QT is greater than 450 msec (JT ≥330 msec if QRS over 100 msec), sotalol hydrochloride tablets (AF) are contraindicated.
- Step 2. Calculation of creatinine clearance: Prior to the administration of the first dose, the patient's creatinine clearance should be calculated using the following formula:
When serum creatinine is given in μmol/L, divide the value by 88.4 (1 mg/dL = 88.4 mcmol/L).
- Step 3. Starting Dose: The starting dose of sotalol hydrochloride tablets (AF) is 80 mg twice daily (BID) if the creatinine clearance is >60 mL/min, and 80 mg once daily (QD) if the creatinine clearance is 40 to 60 mL/min. If the creatinine clearance is <40 mL/min sotalol hydrochloride tablets (AF) are contraindicated.
- Step 4. Administer the appropriate daily dose of sotalol hydrochloride tablets (AF) and begin continuous ECG monitoring with QT interval measurements 2 to 4 hours after each dose.
- Step 5. In patients with a creatinine clearance >60 mL/min, if the 80 mg dose level is tolerated and the QT interval remains <500 msec after at least 3 days (after 5 or 6 doses if patient receiving QD dosing), the patient can be discharged. Alternatively, during hospitalization, the dose can be increased to 100 mg or 120 mg BID and the patient followed for 3 days on this dose (followed for 5 or 6 doses if patient receiving QD doses).
The steps described above are summarized in the following diagram:
- Place Patient on Telemetry
- Check Baseline QT
- If QT >450 msec sotalol hydrochloride tablets (AF) are CONTRAINDICATED
- If QT ≤450 msec, proceed
- Calculate Creatine Clearance (Clcr)
- If Clcr is <40 mL/min sotalol hydrochloride tablets (AF) are CONTRAINDICATED
- If Clcr is 40-60 mL/min start sotalol hydrochloride tablets (AF) 80 mg QD
- If Clcr is >60 mL/min start sotalol hydrochloride tablets (AF) 80 mg BID
- Monitor QT 2 to 4 hours after each dose.
- If QT ≥500 msec discontinue sotalol hydrochloride tablets (AF)
- If QT <500 msec after 3 days (after 5th or 6th dose if patient receiving QD dosing) discharge patient on current treatment. Alternatively, during hospitalization, the dose can be increased to 120 mg BID and the patient followed for 3 days on this dose (followed for 5 or 6 doses if patient receiving QD doses).
- If the 80 mg dose level (given BID or QD depending upon the creatinine clearance) does not reduce the frequency of relapses of AFIB/AFL and is tolerated without excessive QT interval prolongation (i.e., ≥520 msec), the dose level may be increased to 120 mg (BID or QD depending upon the creatinine clearance). As proarrhythmic events can occur not only at initiation of therapy, but also with each upward dosage adjustment, Steps 2 through 5 used during initiation of sotalol hydrochloride tablet (AF) therapy should be followed when increasing the dose level. In the U.S. multicenter dose-response study, the 120 mg dose (BID or QD) was found to be the most effective in prolonging the time to ECG documented symptomatic recurrence of AFIB/AFL. If the 120 mg dose does not reduce the frequency of early relapse of AFIB/AFL and is tolerated without excessive QT interval prolongation (≥520 msec), an increase to 160 mg (BID or QD depending upon the creatinine clearance), can be considered. Steps 2 through 5 used during the initiation of therapy should be used again to introduce such an increase.
- Renal function and QT should be re-evaluated regularly if medically warranted. If QT is 520 msec or greater (JT 430 msec or greater if QRS is > 100 msec), the dose of sotalol hydrochloride tablets (AF) therapy should be reduced and patients should be carefully monitored until QT returns to less than 520 msec. If the QT interval is ≥520 msec while on the lowest maintenance dose level (80 mg) the drug should be discontinued. If renal function deteriorates, reduce the daily dose in half by administering the drug once daily as described in Initiation of sotalol hydrochloride tablets (AF) Therapy, Step 3.
- The maximum recommended dose in patients with a calculated creatinine clearance greater than 60 mL/min is 160 mg BID, doses greater than 160 mg BID have been associated with an increased incidence of Torsade de Pointes and are not recommended.
- A patient who misses a dose should NOT double the next dose. The next dose should be taken at the usual time.
# IV Therapy
- For the safety of the patient, the safety measures required of oral sotalol administration must also be applied for intravenous route. To minimize the risk of induced arrhythmia, patients initiated or re-initiated on sotalol should be hospitalized for at least three days or until steady state drug levels are achieved, in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring. Initiate intravenous sotalol therapy in the presence of personnel trained in the management of serious ventricular arrhythmias. Perform a baseline ECG to determine the QT interval and measure and normalize serum potassium and magnesium levels before initiating therapy with starting sotalol injection. Measure serum creatinine and calculate an estimated creatinine clearance in order to establish the appropriate dosing interval for sotalol.
- If the baseline QT is greater than 450 ms (JT >330 ms if QRS over 100 ms), sotalol is not recommended.
- The patient's creatinine clearance should be calculated using the one of several formulas. The Cockcroft-Gault formula to determine creatinine clearance is:
- When serum creatinine is given in µmol/L, divide the value by 88.4 (1 mg/dL = 88.4 µmol/L).
- Start sotalol therapy only if the baseline QT interval is <450 ms. During initiation and titration, monitor the QT interval after the completion of each infusion If the QT interval prolongs to 500 ms or greater, reduce the dose, decrease the infusion rate, or discontinue the drug.
- Administer sotalol twice daily in patients with a creatinine clearance >60 mL/min or once daily) in patients with a creatinine clearance between 40 and 60 mL/min. Sotalol is not recommended in patients with a creatinine clearance <40 mL/min. The recommended initial IV dose of sotalol is 75 mg (once or twice daily) and is initiated as shown in the dosing algorithm described below. The 75 mg dose can be titrated upward to 112.5 or 150 mg after at least 3 days.
- The bioavailability of oral sotalol is between 90% and 100%. The corresponding dose of intravenous sotalol is, therefore, slightly less than that of the oral dose. The effects of the initial intravenous dose must be monitored and the dose titrated either upward or downward, if needed, based on clinical effect, QT interval, or adverse reactions.
- Intravenous sotalol must be diluted for infusion. Appropriate diluents are saline, 5% dextrose in water (D5W), or Ringer's lactate. Usually, prepare in a volume of 100-250 mL. Use a volumetric infusion pump to infuse intravenous sotalol at a constant rate. The following table compensates for dead space in the infusion set.
- The starting dose of intravenous sotalol is 75 mg infused over 5 hours once or twice daily based on the creatinine clearance. Monitor ECG for excessive increase in QTc.
- If the 75 mg dose of intravenous sotalol does not reduce the frequency of relapses of life threatening ventricular arrhythmias or symptomatic AFIB/AFL and is tolerated without excessive (i.e., to >500 ms) QTc prolongation, increase the dose to 112.5 mg infused over 5 hours, once or twice daily depending upon the creatinine clearance. Continue to monitor QTc during dose escalations.
- The recommended initial dose of intravenous sotalol is 75 mg infused over 5 hours, once or twice daily based on creatinine clearance. The dose may be increased in increments of 75 mg/day every 3 days. The usual therapeutic effect is observed with oral doses of 80 to 160 mg once or twice a day (corresponding to 75 to 150 mg intravenous sotalol). Oral doses as high as 240-320 mg once or twice a day (corresponding to 225 to 300 mg intravenous sotalol) have been utilized in patients with refractory life-threatening arrhythmias.
- In the U.S. multicenter dose-response study, 120 mg orally once or twice a day (corresponding to 112.5 mg intravenous sotalol) was found to be the most effective dose in prolonging the time to ECG-documented symptomatic recurrence of AFIB/AFL. If that dose level, at steady state, does not reduce the frequency of early relapse of arrhythmia and is tolerated without excessive QTc prolongation (>520 ms), increase the dose to 160 mg orally once or twice a day (corresponding to 150 mg intravenous sotalol).
- Dosing Information
- 120 to 480 mg PO q24h.
- 20 mg IV as single dose.
- Dosing Information
- 80 to 320 mg PO q24h.
- As in adults the following precautionary measures should be considered when initiating sotalol treatment in children: initiation of treatment in the hospital after appropriate clinical assessment; individualized regimen as appropriate; gradual increase of doses if required; careful assessment of therapeutic response and tolerability; and frequent monitoring of the QTc interval and heart rate.
- For children aged about 2 years and greater, with normal renal function, doses normalized for body surface area are appropriate for both initial and incremental dosing. Since the Class III potency in children is not very different from that in adults, reaching plasma concentrations that occur within the adult dose range is an appropriate guide. From pediatric pharmacokinetic data the following is recommended.
- For initiation of treatment, 30 mg/m2 three times a day (90 mg/m2 total daily dose) is approximately equivalent to the initial 160 mg total daily dose for adults. Subsequent titration to a maximum of 60 mg/m2 (approximately equivalent to the 360 mg total daily dose for adults) can then occur. Titration should be guided by clinical response, heart rate and QTc, with increased dosing being preferably carried out in-hospital. At least 36 hours should be allowed between dose increments to attain steady-state plasma concentrations of sotalol in patients with age-adjusted normal renal function.
- For children aged about 2 years or younger the above pediatric dosage should be reduced by a factor that depends heavily upon age, as shown in the following graph, age plotted on a logarithmic scale in months.
- For a child aged 20 months, the dosing suggested for children with normal renal function aged 2 years or greater should be multiplied by about 0.97; the initial starting dose would be (30 X 0.97)=29.1 mg/m2, administered three times daily. For a child aged 1 month, the starting dose should be multiplied by 0.68; the initial starting dose would be (30 X 0.68)=20 mg/m2, administered three times daily. For a child aged about 1 week, the initial starting dose should be multiplied by 0.3; the starting dose would be (30 X 0.3)=9 mg/m2. Similar calculations should be made for increased doses as titration proceeds. Since the half-life of sotalol decreases with decreasing age (below about 2 years), time to steady-state will also increase. Thus, in neonates the time to steady-state may be as long as a week or longer.
- In all children, individualization of dosage is required. As in adults sotalol hydrochloride tablets (AF) should be used with particular caution in children if the QTc is greater than 500 msec on therapy and serious consideration should be given to reducing the dose or discontinuing therapy when QTc exceeds 550 msec.
The use of sotalol hydrochloride tablets (AF) in children with renal impairment has not been investigated. Sotalol elimination is predominantly via the kidney in the unchanged form. Use of sotalol in any age group with decreased renal function should be at lower doses or at increased intervals between doses. Monitoring of heart rate and QTc is more important and it will take much longer to reach steady-state with any dose and/or frequency of administration.
- Patients with a history of symptomatic AFIB/AFL who are currently receiving sotalol hydrochloride for the maintenance of normal sinus should be transferred to sotalol hydrochloride tablets (AF) because of the significant differences in labeling (i.e., patient package insert, dosing administration, and safety information).
- Before starting sotalol hydrochloride tablets (AF), previous antiarrhythmic therapy should generally be withdrawn under careful monitoring for a minimum of 2 to 3 plasma half-lives if the patient's clinical condition permits. Treatment has been initiated in some patients receiving I.V. lidocaine without ill effect. After discontinuation of amiodarone, sotalol hydrochloride tablets (AF) should not be initiated until the QT interval is normalized.
Preparation of Extemporaneous Oral Solution
- Sotalol hydrochloride (AF) Syrup 5 mg/mL can be compounded using Simple Syrup containing 0.1% sodium benzoate (Syrup, NF) available from Humco Laboratories as follows:
- Measure 120 mL of Simple Syrup
- Transfer the syrup to a 6-ounce amber plastic (polyethylene terephthalate ) prescription bottle. NOTE: An oversized bottle is used to allow for a headspace, so that there will be more effective mixing during shaking of the bottle.
- Add five (5) sotalol hydrochloride (AF) 120 mg tablets to the bottle. These tablets are added intact; it is not necessary to crush the tablets. NOTE: The addition of the tablets can also be done first. The tablets can also be crushed if preferred. If the tablets are crushed, care should be taken to transfer the entire quantity of tablet powder into the bottle containing the syrup.
- Shake the bottle to wet the entire surface of the tablets. If the tablets have been crushed, shake the bottle until the endpoint is achieved.
- Allow the tablets to hydrate for approximately two hours.
- After at least two hours have elapsed, shake the bottle intermittently over the course of at least another two hours until the tablets are completely disintegrated. NOTE: The tablets can be allowed to hydrate overnight to simplify the disintegration process.
- The endpoint is achieved when a dispersion of fine particles in the syrup is obtained.
- This compounding procedure results in a solution containing 5 mg/mL of sotalol HCl. The fine solid particles are the water-insoluble inactive ingredients of the tablets.
- This extemporaneously prepared oral solution of sotalol HCl (with suspended inactive particles) must be shaken well prior to administration. This is to ensure that the amount of inactive solid particles per dose remains constant throughout the duration of use.
- Stability studies indicate that the suspension is stable when stored at controlled room temperature (15° to 30°C/59° to 86°F) and ambient humidity for three (3) months.
# IV Therapy
- Intravenous sotalol has not been studied in children. As in adults the following precautionary measures should be considered when initiating sotalol treatment in children: initiation of treatment in the hospital after appropriate clinical assessment; individualized regimen as appropriate; gradual increase of doses if required; careful assessment of therapeutic response and tolerability; and frequent monitoring of the QTc interval and heart rate.
- For children aged about 2 years and greater, with normal renal function, doses normalized for body surface area are appropriate for both initial and incremental dosing. Since the Class III potency in children is not very different from that in adults, reaching plasma concentrations that occur within the adult dose range is an appropriate guide. From pediatric pharmacokinetic data the following is recommended. For initiation of treatment, 30 mg/m2 three times a day (90 mg/m2 total daily dose) is approximately equivalent to the initial 160 mg total oral daily dose for adults. Subsequent titration to a maximum of 60 mg/m2 (approximately equivalent to the 360 mg total daily dose for adults) can then occur. Titration should be guided by clinical response, heart rate and QTc, with increased dosing being carried out in-hospital. At least 36 hours should be allowed between dose increments to attain steady-state plasma concentrations of sotalol in patients with age-adjusted normal renal function.
- For children about 2 years or younger the above pediatric dosage should be reduced by a factor that depends heavily upon age, as shown in the following graph which shows age plotted on a logarithmic scale in months.
- For a child aged 20 months, the dosing suggested for children with normal renal function aged 2 years or greater should be multiplied by about 0.97; the initial starting dose would be (30 × 0.97) = 29.1 mg/m2, administered orally three times daily. For a child aged 1 month, the starting dose should be multiplied by 0.68; the initial starting dose would be (30 × 0.68) = 20 mg/m2, administered orally three times daily. For a child aged 1 week, the initial starting oral dose should be multiplied by 0.3; the starting dose would be (30 × 0.3) = 9 mg/m2. Similar calculations should be made for increased doses as titration proceeds. Since the half-life of sotalol decreases with decreasing age (below about 2 years), time to steady-state will also increase. Thus, in neonates the time to steady-state may be as long as a week or longer.
- In all children, individualization of dosage is required. As in adults sotalol should be used with particular caution in children if the QTc is greater than 500 ms on therapy and serious consideration should be given to reducing the dose or discontinuing therapy when QTc exceeds 550 ms.
- The use of oral sotalol in children with renal impairment has not been investigated. Sotalol elimination is predominantly via the kidney in the unchanged form. Use of sotalol in any age group with decreased renal function should be at lower doses or at increased intervals between doses. Monitoring of heart rate and QTc is most important. It will take much longer to reach steady-state with any dose and/or frequency of administration in these children.
- Sinus bradycardia.
- Second degree AV block and third degree AV block, unless a functioning pacemaker is present.
- Congenital or acquired long QT syndromes.
- Cardiogenic shock.
- Uncontrolled congestive heart failure.
- Hypersensitivity to Betapace.
- Sotalol (AF) can cause serious ventricular arrhythmias, primarily Torsade de Pointes (TdP) type ventricular tachycardia, a polymorphic ventricular tachycardia associated with QT interval prolongation. QT interval prolongation is directly related to the dose of sotalol (AF). Factors such as reduced creatinine clearance, gender (female) and larger doses increase the risk of TdP. The risk of TdP can be reduced by adjustment of the sotalol (AF) dose according to creatinine clearance and by monitoring the ECG for excessive increases in the QT interval.
- Treatment with sotalol (AF) must therefore be started only in patients observed for a minimum of three days on their maintenance dose in a facility that can provide electrocardiographic monitoring and in the presence of personnel trained in the management of serious ventricular arrhythmias. Calculation of the creatinine clearance must precede administration of the first dose of sotalol (AF). For detailed instructions regarding dose selection.
- In eight controlled trials of patients with AFIB/AFL and other supraventricular arrhythmias (N=659) there were four cases of Torsade de Pointes reported (0.6%) during the controlled phase of treatment with sotalol (AF). The incidence of Torsade de Pointes was significantly lower in those patients receiving total daily doses of 320 mg or less (0.3%), as summarized in Table 5 below. Both patients who had Torsade de Pointes in the group receiving >320 mg/day were receiving 640 mg/day. In the group receiving ≤320 mg daily, one case of TdP occurred at a daily dose of 320 mg on day 4 of treatment and one case occurred on a daily dose of 160 mg on day 1 of treatment.
- The table below relates the incidence of Torsade de Pointes to on-therapy QTc and change in QTc from baseline. It should be noted, however, that the highest on therapy QTc was in many cases the one obtained at the time of the Torsade de Pointes event, so that the table overstates the predictive value of a high QTc.
- In addition to dose and presence of sustained VT, other risk factors for Torsade de Pointes were gender (females had a higher incidence), excessive prolongation of the QTc interval and history of cardiomegaly or congestive heart failure. Patients with sustained ventricular tachycardia and a history of congestive heart failure appear to have the highest risk for serious proarrhythmia (7%). Of the ventricular arrhythmia patients experiencing Torsade de Pointes, approximately two-thirds spontaneously reverted to their baseline rhythm. The others were either converted electrically (D/C cardioversion or overdrive pacing) or treated with other drugs. It is not possible to determine whether some sudden deaths represented episodes of Torsade de Pointes, but in some instances sudden death did follow a documented episode of Torsade de Pointes. Although sotalol therapy was discontinued in most patients experiencing Torsade de Pointes, 17% were continued on a lower dose.
- The use of sotalo (AF) in conjunction with other drugs that prolong the QT interval has not been studied and is not recommended. Such drugs include many antiarrhythmics, some phenothiazines, bepridil, tricyclic antidepressants, and certain oral macrolides. Class I or Class III antiarrhythmic agents should be withheld for at least three half-lives prior to dosing with sotalol (AF). In clinical trials, sotalots (AF) was not administered to patients previously treated with oral amiodarone for >1 month in the previous three months. Class Ia antiarrhythmic drugs, such as disopyramide, quinidine and procainamide and other Class III drugs (e.g., amiodarone) are not recommended as concomitant therapy with sotalots (AF), because of their potential to prolong refractoriness. There is only limited experience with the concomitant use of Class Ib or Ic antiarrhythmics.
- Sympathetic stimulation is necessary in supporting circulatory function in congestive heart failure, and beta-blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure. In patients who have heart failure controlled by digitalis and/or diuretics, sotalol (AF) should be administered cautiously. Both digitalis and sotalol slow AV conduction. As with all beta-blockers, caution is advised when initiating therapy in patients with any evidence of left ventricular dysfunction. In a pooled data base of four placebo-controlled AFIB/AFL and PSVT studies, new or worsening CHF occurred during therapy with sotalol (AF) in 5 (1.2%) of 415 patients. In these studies patients with uncontrolled heart failure were excluded (i.e., NYHA Functional Classes III or IV). In other premarketing sotalol studies, new or worsened congestive heart failure (CHF) occurred in 3.3% (n=3257) of patients and led to discontinuation in approximately 1% of patients receiving sotalol. The incidence was higher in patients presenting with sustained ventricular tachycardia/ventricular fibrillation (4.6%, n=1363), or a prior history of heart failure (7.3%, n=696). Based on a life-table analysis, the one-year incidence of new or worsened CHF was 3% in patients without a prior history and 10% in patients with a prior history of CHF. NYHA Classification was also closely associated to the incidence of new or worsened heart failure while receiving sotalol (1.8% in 1395 Class I patients, 4.9% in 1254 Class II patients and 6.1% in 278 Class III or IV patients).
- Sotalol (AF) should not be used in patients with hypokalemia or hypomagnesemia prior to correction of imbalance, as these conditions can exaggerate the degree of QT prolongation, and increase the potential for Torsade de Pointes. Special attention should be given to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or patients receiving concomitant diuretic drugs.
- The incidence of bradycardia (as determined by the investigators) in the supraventricular arrhythmia population treated with sotalol (AF) (N = 415) was 13%, and led to discontinuation in 2.4% of patients. Bradycardia itself increases the risk of Torsade de Pointes.
- Sotalol has been used in a controlled trial following an acute myocardial infarction without evidence of increased mortality (see Safety in Patients with Structural Heart Disease). Although specific studies of its use in treating atrial arrhythmias after infarction have not been conducted, the usual precautions regarding heart failure, avoidance of hypokalemia, bradycardia or prolonged QT interval apply.
- Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy. Occasional cases of exacerbation of angina pectoris, arrhythmias and, in some cases, myocardial infarction have been reported after abrupt discontinuation of beta-blocker therapy. Therefore, it is prudent when discontinuing chronically administered sotalol (AF), particularly in patients with ischemic heart disease, to carefully monitor the patient and consider the temporary use of an alternate beta-blocker if appropriate. If possible, the dosage of sotalol (AF) should be gradually reduced over a period of one to two weeks. If angina or acute coronary insufficiency develops, appropriate therapy should be instituted promptly. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized in patients receiving sotalols (AF), abrupt discontinuation in patients with arrhythmias may unmask latent coronary insufficiency.
- PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD IN GENERAL NOT RECEIVE BETA-BLOCKERS. It is prudent, if sotalol hydrochloride (AF) is to be administered, to use the smallest effective dose, so that inhibition of bronchodilation produced by endogenous or exogenous catecholamine stimulation of beta2 receptors may be minimized.
- While taking beta-blockers, patients with a history of anaphylactic reaction to a variety of allergens may have a more severe reaction on repeated challenge, either accidental, diagnostic or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat the allergic reaction.
- Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.
- In patients with diabetes (especially labile diabetes) or with a history of episodes of spontaneous hypoglycemia, sotalol (AF) should be given with caution since beta-blockade may mask some important premonitory signs of acute hypoglycemia; e.g., tachycardia.
- Sotalol (AF) should be used only with extreme caution in patients with sick sinus syndrome associated with symptomatic arrhythmias, because it may cause sinus bradycardia, sinus pauses or sinus arrest. In patients with AFIB and sinus node dysfunction, the risk of Torsade de Pointes with sotalol (AF) therapy is increased, especially after cardioversion. Bradycardia following cardioversion in these patients is associated with QTc interval prolongation which is augmented due to the reverse use dependence of the Class III effects of sotalol (AF). Patients with AFIB/AFL associated with the sick sinus syndrome may be treated with sotalol (AF) if they have an implanted pacemaker for control of bradycardia symptoms.
- Beta-blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-blockade which might be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm. The beta-blocking effects of sotalol (AF) may be useful in controlling heart rate in AFIB associated with thyrotoxicosis but no study has been conducted to evaluate this.
- In a pooled clinical trial population consisting of four placebo-controlled studies with 275 patients with AFIB/AFL treated with 160 to 320 mg doses of sotalol hydrochloride (AF), the following adverse events were reported at a rate of 2% or more in the 160-240 mg treated patients and greater than the rate in placebo patients (See Table 8). The data are presented by incidence of events in the sotalol (AF) and placebo groups by body system and daily dose. No significant irreversible non-cardiac end-organ toxicity was observed.
- Overall, discontinuation because of unacceptable adverse events was necessary in 17% of the patients, and occurred in 10% of patients less than two weeks after starting treatment. The most common adverse events leading to discontinuation of sotalol hydrochloride (AF) were: fatigue 4.6%, bradycardia 2.4%, proarrhythmia 2.2%, dyspnea 2%, and QT interval prolongation 1.4%.
- In clinical trials involving 1292 patients with sustained VT/VF, the common adverse events (occurring in ≥2% of patients) were similar to those described for the AFIB/AFL population.
- Occasional reports of elevated serum liver enzymes have occurred with sotalol therapy but no cause and effect relationship has been established. One case of peripheral neuropathy which resolved on discontinuation of sotalol and recurred when the patient was rechallenged with the drug was reported in an early dose tolerance study. Elevated blood glucose levels and increased insulin requirements can occur in diabetic patients.
- In an unblinded multicenter trial of 25 patients with SVT and/or VT receiving daily doses of 30, 90 and 210 mg/m2 with dosing every 8 hours for a total of 9 doses, no Torsades de Pointes or other serious new arrhythmias were observed. One (1) patient, receiving 30 mg/m2 daily, was discontinued because of increased frequency of sinus pauses/bradycardia. Additional cardiovascular AEs were seen at the 90 and 210 mg/m2 daily dose levels. They included QT prolongations (2 patients), sinus pauses/bradycardia (1 patient), increased severity of atrial flutter and reported chest pain (1 patient). Values for QTc ≥525 msec were seen in 2 patients at the 210 mg/m2 daily dose level. Serious adverse events including death, Torsades de Pointes, other proarrhythmias, high-degree AV blocks and bradycardia have been reported in infants and/or children.
- Foreign marketing experience with sotalol hydrochloride shows an adverse experience profile similar to that described above from clinical trials. Voluntary reports since introduction also include rare reports of: emotional liability, slightly clouded sensorium, incoordination, vertigo, paralysis, thrombocytopenia, eosinophilia, leukopenia, photosensitivity reaction, fever, pulmonary edema, hyperlipidemia, myalgia, pruritis, alopecia.
- The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been associated with sotalol (AF) during investigational use and foreign marketing experience.
- Digoxin: Proarrhythmic events were more common in sotalol treated patients also receiving digoxin; it is not clear whether this represents an interaction or is related to the presence of CHF, a known risk factor for proarrhythmia, in the patients receiving digoxin. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.
- Calcium blocking drugs: Sotalol (AF) should be administered with caution in conjunction with calcium blocking drugs because of possible additive effects on atrioventricular conduction or ventricular function. Additionally, concomitant use of these drugs may have additive effects on blood pressure, possibly leading to hypotension.
- Catecholamine-depleting agents: Concomitant use of catecholamine-depleting drugs, such as reserpine and guanethidine, with a beta-blocker may produce an excessive reduction of resting sympathetic nervous tone. Patients treated with sotalol (AF) plus a catecholamine depletor should therefore be closely monitored for evidence of hypotension and/or marked bradycardia which may produce syncope.
- Insulin and oral antidiabetics: Hyperglycemia may occur, and the dosage of insulin or antidiabetic drugs may require adjustment. Symptoms of hypoglycemia may be masked.
- Beta-2-receptor stimulants: Beta-agonists such as salbutamol, terbutaline and isoprenaline may have to be administered in increased dosages when used concomitantly with sotalol (AF).
- Clonidine: Beta-blocking drugs may potentiate the rebound hypertension sometimes observed after discontinuation of clonidine; therefore, caution is advised when discontinuing clonidine in patients receiving sotalol (AF).
- Other: No pharmacokinetic interactions were observed with hydrochlorothiazide or warfarin.
- Antacids: Administration of sotalol (AF) within 2 hours of antacids containing aluminum oxide and magnesium hydroxide should be avoided because it may result in a reduction in Cmax and AUC of 26% and 20%, respectively and consequently in a 25% reduction in the bradycardic effect at rest. Administration of the antacid two hours after sotalol (AF) has no effect on the pharmacokinetics or pharmacodynamics of sotalol.
- Drug/Laboratory Test Interactions: The presence of sotalol in the urine may result in falsely elevated levels of urinary metanephrine when measured by fluorimetric or photometric methods. In screening patients suspected of having a pheochromocytoma and being treated with sotalol, a specific method, such as a high performance liquid chromatographic assay with solid phase extraction (e.g., J. Chromatogr. 385:241, 1987) should be employed in determining levels of catecholamines.
- Although there are no adequate and well-controlled studies in pregnant women, sotalol HCl has been shown to cross the placenta, and is found in amniotic fluid. There has been a report of subnormal birth weight with sotalol. Therefore, sotalol (AF) should be used during pregnancy only if the potential benefit outweighs the potential risk.
- Administer the appropriate daily dose of sotalol hydrochloride tablets (AF) and begin continuous ECG monitoring with QT interval measurements 2 to 4 hours after each dose.
- The most common signs to be expected are bradycardia, congestive heart failure, hypotension, bronchospasm and hypoglycemia. In cases of massive intentional overdosage (2 to 16 grams) of sotalol the following clinical findings were seen: hypotension, bradycardia, cardiac asystole, prolongation of QT interval, Torsade de Pointes, ventricular tachycardia, and premature ventricular complexes. If overdosage occurs, therapy with sotalol (AF) should be discontinued and the patient observed closely. Because of the lack of protein binding, hemodialysis is useful for reducing sotalol plasma concentrations. Patients should be carefully observed until QT intervals are normalized and the heart rate returns to levels >50 bpm. The occurrence of hypotension following an overdose may be associated with an initial slow drug elimination phase (half life of 30 hours) thought to be due to a temporary reduction of renal function caused by the hypotension. In addition, if required, the following therapeutic measures are suggested:
- Bradycardia or Cardiac Asystole: Atropine, another anticholinergic drug, a beta-agonist or transvenous cardiac pacing.
- Heart Block: Second degree AV block and third degree AV block transvenous cardiac pacemaker.
- Hypotension: (depending on associated factors) epinephrine rather than isoproterenol or norepinephrine may be useful.
- Bronchospasm: Aminophylline or aerosol beta2-stimulant.
- Torsade de Pointes: DC cardioversion, transvenous cardiac pacing, epinephrine, magnesium sulfate.
- In children, a Class III electrophysiologic effect can be seen at daily doses of 210 mg/m2 body surface area (BSA). A reduction of the resting heart rate due to the beta-blocking effect of sotalol is observed at daily doses ≥ 90 mg/m2 in children.
- Satolol tablets contain the following inactive ingredients: microcrystalline cellulose, lactose, starch, stearic acid, magnesium stearate, colloidal silicon dioxide, and FD&C blue color #2 (aluminum lake, conc.).
- In man, the Class II (beta-blockade) electrophysiological effects of sotalol are manifested by increased sinus cycle length (slowed heart rate]), decreased AV nodal conduction and increased AV nodal refractoriness. The Class III electrophysiological effects in man include prolongation of the atrial and ventricular monophasic action potentials, and effective refractory period prolongation of atrial muscle, ventricular muscle, and atrio-ventricular accessory pathways (where present) in both the anterograde and retrograde directions. With oral doses of 160 to 640 mg/day, the surface ECG shows dose-related mean increases of 40-100 msec in QT and 10-40 msec in QTc. No significant alteration in QRS interval is observed.
- In a small study (n=25) of patients with implanted defibrillators treated concurrently with sotalol, the average defibrillatory threshold was 6 joules (range 2-15 joules) compared to a mean of 16 joules for a nonrandomized comparative group primarily receiving amiodarone.
- Twenty-five children in an unblinded, multicenter trial with supraventricular tachycardias (SVT) and/or ventricular tachyarrhythmias (VT), aged between 3 days and 12 years (mostly neonates and infants), received an ascending titration regimen with daily doses of 30, 90 and 210 mg/m2 with dosing every 8 hours for a total 9 doses. During steady-state, the respective average increases above baseline of the QTc interval, in msec (%), were 2(+1%), 14(+4%) and 29(+7%) msec at the 3 dose levels. The respective mean maximum increases above baseline of the QTc interval, in msec (%), were 23(+6%), 36(+9%) and 55(+14%) msec at the 3 dose levels. The steadystate percent increases in the RR interval were 3, 9 and 12%. The smallest children (BSA<0.33m2) showed a tendency for larger Class III effects (ΔQTc) and an increased frequency of prolongations of the QTc interval as compared with larger children (BSA≥0.33m2). The beta-blocking effects also tended to be greater in the smaller children (BSA<0.33m2). Both the Class III and beta-blocking effects of sotalol were linearly related with the plasma concentrations.
- Sotalol hydrochloride does not bind to plasma proteins and is not metabolized. Sotalol hydrochloride shows very little intersubject variability in plasma levels. The pharmacokinetics of the d and l enantiomers of sotalol are essentially identical. Sotalol hydrochloride crosses the blood brain barrier poorly. Excretion is predominantly via the kidney in the unchanged form, and therefore lower doses are necessary in conditions of renal impairment. Age per se does not significantly alter the pharmacokinetics of sotalol, but impaired renal function in geriatric patients can increase the terminal elimination half-life, resulting in increased drug accumulation. The absorption of sotalol hydrochloride was reduced by approximately 20% compared to fasting when it was administered with a standard meal. Since sotalol hydrochloride is not subject to first-pass metabolism, patients with hepatic impairment show no alteration in clearance of sotalol.
- The combined analysis of two unblinded, multicenter trials (a single dose and a multiple dose study) with 59 children, aged between 3 days and 12 years, showed the pharmacokinetics of sotalol to be first order. A daily dose of 30 mg/m2 of sotalol was administered in the single dose study and daily doses of 30, 90 and 210 mg/m2 were administered q 8h in the multi-dose study. After rapid absorption with peak levels occurring on average between 2-3 hours following administration, sotalol was eliminated with a mean half life of 9.5 hours. Steady-state was reached after 1-2 days. The average peak to trough concentration ratio was 2. BSA was the most important covariate and more relevant than age for the pharmacokinetics of sotalol.The smallest children (BSA<0.33m2) exhibited a greater drug exposure (+59%) than the larger children who showed a uniform drug concentration profile. The intersubject variation for oral clearance was 22%.
- Sotalol has not been evaluated in any specific assay of mutagenicity or clastogenicity.
- No significant reduction in fertility occurred in rats at oral doses of 1000 mg/kg/ day (approximately 100 times the MRHD as mg/kg or 9 times the MRHD as mg/m2) prior to mating, except for a small reduction in the number of offspring per litter.
- Sotalol hydrochloride (AF) has been studied in patients with symptomatic AFIB/AFL in two principal studies, one in patients with primarily paroxysmal AFIB/AFL, the other in patients with primarily chronic AFIB.
- In one study, a U.S. multicenter, randomized, placebo-controlled, double-blind, dose-response trial of patients with symptomatic primarily paroxysmal AFIB/AFL, three fixed dose levels of sotalol hydrochloride (AF) (80 mg, 120 mg and 160 mg) twice daily and placebo were compared in 253 patients. In patients with reduced creatinine clearance (40-60 mL/min) the same doses were given once daily. Patients were not randomized for the following reasons: QT >450 msec; creatinine clearance 1 month within previous 12 weeks; congenital or acquired long QT syndromes; history of Torsade de Pointes with other antiarrhythmic agents which increase the duration of ventricular repolarization; sinus rate 100 msec) the drug was discontinued. The patient population in this trial was 64% male, and the mean age was 62 years. No structural heart disease was present in 43% of the patients. Doses were administered once daily in 20% of the patients because of reduced creatinine clearance.
- Sotalol hydrochloride (AF) was shown to prolong the time to the first symptomatic, ECG documented recurrence of AFIB/AFL, as well as to reduce the risk of such recurrence at both 6 and 12 months. The 120 mg dose was more effective than 80 mg, but 160 mg did not appear to have an added benefit. Note that these doses were given twice or once daily, depending on renal function. The results are shown in the figure and tables below.
Please note that columns do not add up to 100% due to discontinuations (D/C) for "other" reasons.
Discontinuation because of adverse events was dose related.
- In a second multicenter, randomized, placebo-controlled, double-blind study of 6 months duration in 232 patients with chronic AFIB, sotalol hydrochloride (AF) was titrated over a dose range from 80 mg/day to 320 mg/day. The patient population of this trial was 70% male with a mean age of 65 years. Structural heart disease was present in 49% of the patients. All patients had chronic AFIB for >2 weeks but 460 msec, QRS >140 msec, any degree of AV block or functioning pacemaker, uncompensated cardiac failure, asthma, significant renal disease (estimated creatinine clearance <50 mL/min), heart rate <50 bpm, myocardial infarction or open heart surgery in past 2 months, unstable angina, infective endocarditis, active pericarditis or myocarditis, ≥ 3 DC cardioversions in the past, medications that prolonged QT interval, and previous amiodarone treatment. After successful cardioversion patients were randomized to receive placebo (n=114) or sotalol hydrochloride (AF) (n=118), at a starting dose of 80 mg twice daily. If the initial dose was not tolerated it was decreased to 80 mg once daily, but if it was tolerated it was increased to 160 mg twice daily. During the maintenance period 67% of treated patients received a dose of 160 mg twice daily, and the remainder received doses of 80 mg once daily (17%) and 80 mg twice daily (16%).
- The figure and Tables below show the results of the trial. There was a longer time to ECG-documented recurrence of AFIB and a reduced risk of recurrence at 6 months compared to placebo.
- In a multicenter double-blind randomized study reported by D. Julian et al, the effect of sotalol 320 mg once daily was compared with that of placebo in 1456 patients (randomized 3:2, sotalol to placebo) surviving an acute myocardial infarction (MI). Treatment was started 5 to 14 days after infarction. Patients were followed for 12 months. The mortality rate was 7.3% in the sotalol group and 8.9% in the placebo group, not a statistically significant difference. Although the results do not show evidence of a benefit of sotalol in this population, they do not show an added risk in post MI patients receiving sotalol.
- Betapace (sotalol hydrochloride); capsule-shaped light-blue scored tablets imprinted with the strength and “Betapace”, are available as follows:
- 80 mg strength, bottle of 100 (NDC 50419-105-10)
- 120 mg strength, bottle of 100 (NDC 50419-109-10)
- 160 mg strength, bottle of 100 (NDC 50419-106-10)
- Intravenous sotalol is supplied in 10 mL vials, each containing 150 mg sotalol hydrochloride (15 mg/mL).
- Each vial is individually packed in a carton (NDC 67457-176-10).
- Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).
- Store at 25°C (77°F) with excursions permitted to 15°-30° C (59°-86°F).
- Protect from freezing and light
Medications and Supplements
- Assessment of patients' medication history should include all over-counter, prescription and herbal/natural preparations with emphasis on preparations that may affect the pharmacodynamics of sotalol (AF) such as other cardiac antiarrhythmic drugs, some phenothiazines, bepridil, tricyclic antidepressants and oral macrolides. Patients should be instructed to notify their health care providers of any change in over-the-counter, prescription or supplement use. If a patient is hospitalized or is prescribed a new medication for any condition, the patient must inform the health care provider of ongoing sotalol (AF) therapy. Patients should also check with their health care provider and/or pharmacist prior to taking a new over-the-counter medicine.
Electrolyte Imbalance
- If patients experience symptoms that may be associated with electrolyte disturbances, such as excessive or prolonged diarrhea, sweating, or vomiting, or loss of appetite or thirst, these conditions should be immediately reported to their health care provider.
Dosing Schedule
- Patients should be instructed NOT to double the next dose if a dose is missed. The next dose should be taken at the usual time.
- Betapace AF
- Sorine
- ↑ Gooding PG, Berman E (1974). "An evaluation of sotalol, a beta-blocking agent, in patients with angina pectoris". Postgrad Med J. 50 (590): 734–6. PMC 2496011. PMID 4157126.CS1 maint: PMC format (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Areskog NH, Cullhed I, Ringqvist I, Ström G (1975). "Cardiovascular and respiratory effects of the beta-adrenoceptive antagonist sotalol: studies in health, angina pectoris and obstructive lung disease". Eur J Clin Pharmacol. 8 (6): 403–8. PMID 1233240.CS1 maint: Multiple names: authors list (link)
- ↑ Parvinen I, Paukkala E (1979). "Thrice-daily blood pressure readings on sotalol in the treatment of hypertension: once- versus twice-daily regimen". J Clin Pharmacol. 19 (8-9 Pt 2): 533–9. PMID 489772. | Sotalol
- Therapy with sotalol hydrochloride tablets (AF) must be initiated (and, if necessary, titrated) in a setting that provides continuous electrocardiographic (ECG) monitoring and in the presence of personnel trained in the management of serious ventricular arrhythmias. Patients should continue to be monitored in this way for a minimum of 3 days on the maintenance dose. In addition, patients should not be discharged within 12 hours of electrical or pharmacological conversion to normal sinus rhythm.
- The QT interval is used to determine patient eligibility for sotalol hydrochloride tablets (AF) treatment and for monitoring safety during treatment. The baseline QT interval must be ≤450 msec in order for a patient to be started on sotalol hydrochloride tablets (AF) therapy. During initiation and titration, the QT interval should be monitored 2 to 4 hours after each dose. If the QT interval prolongs to 500 msec or greater, the dose must be reduced or the drug discontinued.
- The dose of sotalol hydrochloride tablets, USP (AF) must be individualized according to calculated creatinine clearance. In patients with a creatinine clearance >60 mL/min sotalol hydrochloride tablets (AF) are administered twice daily (BID) while in those with a creatinine clearance between 40 and 60 mL/min, the dose is administered once daily (QD) or half the dose is administered twice daily (BID). In patients with a creatinine clearance less than 40 mL/min sotalol hydrochloride tablets (AF) are contraindicated. The recommended initial dose of sotalol hydrochloride tablets (AF) is 80 mg and is initiated as shown in the dosing algorithm described below. The 80 mg dose can be titrated upward to 100 mg or 120 mg during initial hospitalization or after discharge on 80 mg in the event of recurrence, by rehospitalization and repeating the same steps used during the initiation of therapy.
- Patients with atrial fibrillation should be anticoagulated according to usual medical practice. Hypokalemia should be corrected before initiation of sotalol hydrochloride tablets (AF) therapy.
- Patients to be discharged on sotalol hydrochloride tablets (AF) therapy from an in-patient setting should have an adequate supply of sotalol hydrochloride tablets (AF), to allow uninterrupted therapy until the patient can fill a sotalol hydrochloride tablets (AF) prescription.
- Step 1. Electrocardiographic assessment: Prior to administration of the first dose, the QT interval must be determined using an average of 5 beats. If the baseline QT is greater than 450 msec (JT ≥330 msec if QRS over 100 msec), sotalol hydrochloride tablets (AF) are contraindicated.
- Step 2. Calculation of creatinine clearance: Prior to the administration of the first dose, the patient's creatinine clearance should be calculated using the following formula:
When serum creatinine is given in μmol/L, divide the value by 88.4 (1 mg/dL = 88.4 mcmol/L).
- Step 3. Starting Dose: The starting dose of sotalol hydrochloride tablets (AF) is 80 mg twice daily (BID) if the creatinine clearance is >60 mL/min, and 80 mg once daily (QD) if the creatinine clearance is 40 to 60 mL/min. If the creatinine clearance is <40 mL/min sotalol hydrochloride tablets (AF) are contraindicated.
- Step 4. Administer the appropriate daily dose of sotalol hydrochloride tablets (AF) and begin continuous ECG monitoring with QT interval measurements 2 to 4 hours after each dose.
- Step 5. In patients with a creatinine clearance >60 mL/min, if the 80 mg dose level is tolerated and the QT interval remains <500 msec after at least 3 days (after 5 or 6 doses if patient receiving QD dosing), the patient can be discharged. Alternatively, during hospitalization, the dose can be increased to 100 mg or 120 mg BID and the patient followed for 3 days on this dose (followed for 5 or 6 doses if patient receiving QD doses).
The steps described above are summarized in the following diagram:
- Place Patient on Telemetry
- Check Baseline QT
- If QT >450 msec sotalol hydrochloride tablets (AF) are CONTRAINDICATED
- If QT ≤450 msec, proceed
- Calculate Creatine Clearance (Clcr)
- If Clcr is <40 mL/min sotalol hydrochloride tablets (AF) are CONTRAINDICATED
- If Clcr is 40-60 mL/min start sotalol hydrochloride tablets (AF) 80 mg QD
- If Clcr is >60 mL/min start sotalol hydrochloride tablets (AF) 80 mg BID
- Monitor QT 2 to 4 hours after each dose.
- If QT ≥500 msec discontinue sotalol hydrochloride tablets (AF)
- If QT <500 msec after 3 days (after 5th or 6th dose if patient receiving QD dosing) discharge patient on current treatment. Alternatively, during hospitalization, the dose can be increased to 120 mg BID and the patient followed for 3 days on this dose (followed for 5 or 6 doses if patient receiving QD doses).
- If the 80 mg dose level (given BID or QD depending upon the creatinine clearance) does not reduce the frequency of relapses of AFIB/AFL and is tolerated without excessive QT interval prolongation (i.e., ≥520 msec), the dose level may be increased to 120 mg (BID or QD depending upon the creatinine clearance). As proarrhythmic events can occur not only at initiation of therapy, but also with each upward dosage adjustment, Steps 2 through 5 used during initiation of sotalol hydrochloride tablet (AF) therapy should be followed when increasing the dose level. In the U.S. multicenter dose-response study, the 120 mg dose (BID or QD) was found to be the most effective in prolonging the time to ECG documented symptomatic recurrence of AFIB/AFL. If the 120 mg dose does not reduce the frequency of early relapse of AFIB/AFL and is tolerated without excessive QT interval prolongation (≥520 msec), an increase to 160 mg (BID or QD depending upon the creatinine clearance), can be considered. Steps 2 through 5 used during the initiation of therapy should be used again to introduce such an increase.
- Renal function and QT should be re-evaluated regularly if medically warranted. If QT is 520 msec or greater (JT 430 msec or greater if QRS is > 100 msec), the dose of sotalol hydrochloride tablets (AF) therapy should be reduced and patients should be carefully monitored until QT returns to less than 520 msec. If the QT interval is ≥520 msec while on the lowest maintenance dose level (80 mg) the drug should be discontinued. If renal function deteriorates, reduce the daily dose in half by administering the drug once daily as described in Initiation of sotalol hydrochloride tablets (AF) Therapy, Step 3.
- The maximum recommended dose in patients with a calculated creatinine clearance greater than 60 mL/min is 160 mg BID, doses greater than 160 mg BID have been associated with an increased incidence of Torsade de Pointes and are not recommended.
- A patient who misses a dose should NOT double the next dose. The next dose should be taken at the usual time.
## IV Therapy
- For the safety of the patient, the safety measures required of oral sotalol administration must also be applied for intravenous route. To minimize the risk of induced arrhythmia, patients initiated or re-initiated on sotalol should be hospitalized for at least three days or until steady state drug levels are achieved, in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring. Initiate intravenous sotalol therapy in the presence of personnel trained in the management of serious ventricular arrhythmias. Perform a baseline ECG to determine the QT interval and measure and normalize serum potassium and magnesium levels before initiating therapy with starting sotalol injection. Measure serum creatinine and calculate an estimated creatinine clearance in order to establish the appropriate dosing interval for sotalol.
- If the baseline QT is greater than 450 ms (JT >330 ms if QRS over 100 ms), sotalol is not recommended.
- The patient's creatinine clearance should be calculated using the one of several formulas. The Cockcroft-Gault formula to determine creatinine clearance is:
- When serum creatinine is given in µmol/L, divide the value by 88.4 (1 mg/dL = 88.4 µmol/L).
- Start sotalol therapy only if the baseline QT interval is <450 ms. During initiation and titration, monitor the QT interval after the completion of each infusion If the QT interval prolongs to 500 ms or greater, reduce the dose, decrease the infusion rate, or discontinue the drug.
- Administer sotalol twice daily in patients with a creatinine clearance >60 mL/min or once daily) in patients with a creatinine clearance between 40 and 60 mL/min. Sotalol is not recommended in patients with a creatinine clearance <40 mL/min. The recommended initial IV dose of sotalol is 75 mg (once or twice daily) and is initiated as shown in the dosing algorithm described below. The 75 mg dose can be titrated upward to 112.5 or 150 mg after at least 3 days.
- The bioavailability of oral sotalol is between 90% and 100%. The corresponding dose of intravenous sotalol is, therefore, slightly less than that of the oral dose. The effects of the initial intravenous dose must be monitored and the dose titrated either upward or downward, if needed, based on clinical effect, QT interval, or adverse reactions.
- Intravenous sotalol must be diluted for infusion. Appropriate diluents are saline, 5% dextrose in water (D5W), or Ringer's lactate. Usually, prepare in a volume of 100-250 mL. Use a volumetric infusion pump to infuse intravenous sotalol at a constant rate. The following table compensates for dead space in the infusion set.
- The starting dose of intravenous sotalol is 75 mg infused over 5 hours once or twice daily based on the creatinine clearance. Monitor ECG for excessive increase in QTc.
- If the 75 mg dose of intravenous sotalol does not reduce the frequency of relapses of life threatening ventricular arrhythmias or symptomatic AFIB/AFL and is tolerated without excessive (i.e., to >500 ms) QTc prolongation, increase the dose to 112.5 mg infused over 5 hours, once or twice daily depending upon the creatinine clearance. Continue to monitor QTc during dose escalations.
- The recommended initial dose of intravenous sotalol is 75 mg infused over 5 hours, once or twice daily based on creatinine clearance. The dose may be increased in increments of 75 mg/day every 3 days. The usual therapeutic effect is observed with oral doses of 80 to 160 mg once or twice a day (corresponding to 75 to 150 mg intravenous sotalol). Oral doses as high as 240-320 mg once or twice a day (corresponding to 225 to 300 mg intravenous sotalol) have been utilized in patients with refractory life-threatening arrhythmias.
- In the U.S. multicenter dose-response study, 120 mg orally once or twice a day (corresponding to 112.5 mg intravenous sotalol) was found to be the most effective dose in prolonging the time to ECG-documented symptomatic recurrence of AFIB/AFL. If that dose level, at steady state, does not reduce the frequency of early relapse of arrhythmia and is tolerated without excessive QTc prolongation (>520 ms), increase the dose to 160 mg orally once or twice a day (corresponding to 150 mg intravenous sotalol).
- Dosing Information
- 120 to 480 mg PO q24h.[1]
- 20 mg IV as single dose.[2]
- Dosing Information
- 80 to 320 mg PO q24h.[3]
- As in adults the following precautionary measures should be considered when initiating sotalol treatment in children: initiation of treatment in the hospital after appropriate clinical assessment; individualized regimen as appropriate; gradual increase of doses if required; careful assessment of therapeutic response and tolerability; and frequent monitoring of the QTc interval and heart rate.
- For children aged about 2 years and greater, with normal renal function, doses normalized for body surface area are appropriate for both initial and incremental dosing. Since the Class III potency in children is not very different from that in adults, reaching plasma concentrations that occur within the adult dose range is an appropriate guide. From pediatric pharmacokinetic data the following is recommended.
- For initiation of treatment, 30 mg/m2 three times a day (90 mg/m2 total daily dose) is approximately equivalent to the initial 160 mg total daily dose for adults. Subsequent titration to a maximum of 60 mg/m2 (approximately equivalent to the 360 mg total daily dose for adults) can then occur. Titration should be guided by clinical response, heart rate and QTc, with increased dosing being preferably carried out in-hospital. At least 36 hours should be allowed between dose increments to attain steady-state plasma concentrations of sotalol in patients with age-adjusted normal renal function.
- For children aged about 2 years or younger the above pediatric dosage should be reduced by a factor that depends heavily upon age, as shown in the following graph, age plotted on a logarithmic scale in months.
- For a child aged 20 months, the dosing suggested for children with normal renal function aged 2 years or greater should be multiplied by about 0.97; the initial starting dose would be (30 X 0.97)=29.1 mg/m2, administered three times daily. For a child aged 1 month, the starting dose should be multiplied by 0.68; the initial starting dose would be (30 X 0.68)=20 mg/m2, administered three times daily. For a child aged about 1 week, the initial starting dose should be multiplied by 0.3; the starting dose would be (30 X 0.3)=9 mg/m2. Similar calculations should be made for increased doses as titration proceeds. Since the half-life of sotalol decreases with decreasing age (below about 2 years), time to steady-state will also increase. Thus, in neonates the time to steady-state may be as long as a week or longer.
- In all children, individualization of dosage is required. As in adults sotalol hydrochloride tablets (AF) should be used with particular caution in children if the QTc is greater than 500 msec on therapy and serious consideration should be given to reducing the dose or discontinuing therapy when QTc exceeds 550 msec.
The use of sotalol hydrochloride tablets (AF) in children with renal impairment has not been investigated. Sotalol elimination is predominantly via the kidney in the unchanged form. Use of sotalol in any age group with decreased renal function should be at lower doses or at increased intervals between doses. Monitoring of heart rate and QTc is more important and it will take much longer to reach steady-state with any dose and/or frequency of administration.
- Patients with a history of symptomatic AFIB/AFL who are currently receiving sotalol hydrochloride for the maintenance of normal sinus should be transferred to sotalol hydrochloride tablets (AF) because of the significant differences in labeling (i.e., patient package insert, dosing administration, and safety information).
- Before starting sotalol hydrochloride tablets (AF), previous antiarrhythmic therapy should generally be withdrawn under careful monitoring for a minimum of 2 to 3 plasma half-lives if the patient's clinical condition permits. Treatment has been initiated in some patients receiving I.V. lidocaine without ill effect. After discontinuation of amiodarone, sotalol hydrochloride tablets (AF) should not be initiated until the QT interval is normalized.
Preparation of Extemporaneous Oral Solution
- Sotalol hydrochloride (AF) Syrup 5 mg/mL can be compounded using Simple Syrup containing 0.1% sodium benzoate (Syrup, NF) available from Humco Laboratories as follows:
- Measure 120 mL of Simple Syrup
- Transfer the syrup to a 6-ounce amber plastic (polyethylene terephthalate [PET]) prescription bottle. NOTE: An oversized bottle is used to allow for a headspace, so that there will be more effective mixing during shaking of the bottle.
- Add five (5) sotalol hydrochloride (AF) 120 mg tablets to the bottle. These tablets are added intact; it is not necessary to crush the tablets. NOTE: The addition of the tablets can also be done first. The tablets can also be crushed if preferred. If the tablets are crushed, care should be taken to transfer the entire quantity of tablet powder into the bottle containing the syrup.
- Shake the bottle to wet the entire surface of the tablets. If the tablets have been crushed, shake the bottle until the endpoint is achieved.
- Allow the tablets to hydrate for approximately two hours.
- After at least two hours have elapsed, shake the bottle intermittently over the course of at least another two hours until the tablets are completely disintegrated. NOTE: The tablets can be allowed to hydrate overnight to simplify the disintegration process.
- The endpoint is achieved when a dispersion of fine particles in the syrup is obtained.
- This compounding procedure results in a solution containing 5 mg/mL of sotalol HCl. The fine solid particles are the water-insoluble inactive ingredients of the tablets.
- This extemporaneously prepared oral solution of sotalol HCl (with suspended inactive particles) must be shaken well prior to administration. This is to ensure that the amount of inactive solid particles per dose remains constant throughout the duration of use.
- Stability studies indicate that the suspension is stable when stored at controlled room temperature (15° to 30°C/59° to 86°F) and ambient humidity for three (3) months.
## IV Therapy
- Intravenous sotalol has not been studied in children. As in adults the following precautionary measures should be considered when initiating sotalol treatment in children: initiation of treatment in the hospital after appropriate clinical assessment; individualized regimen as appropriate; gradual increase of doses if required; careful assessment of therapeutic response and tolerability; and frequent monitoring of the QTc interval and heart rate.
- For children aged about 2 years and greater, with normal renal function, doses normalized for body surface area are appropriate for both initial and incremental dosing. Since the Class III potency in children is not very different from that in adults, reaching plasma concentrations that occur within the adult dose range is an appropriate guide. From pediatric pharmacokinetic data the following is recommended. For initiation of treatment, 30 mg/m2 three times a day (90 mg/m2 total daily dose) is approximately equivalent to the initial 160 mg total oral daily dose for adults. Subsequent titration to a maximum of 60 mg/m2 (approximately equivalent to the 360 mg total daily dose for adults) can then occur. Titration should be guided by clinical response, heart rate and QTc, with increased dosing being carried out in-hospital. At least 36 hours should be allowed between dose increments to attain steady-state plasma concentrations of sotalol in patients with age-adjusted normal renal function.
- For children about 2 years or younger the above pediatric dosage should be reduced by a factor that depends heavily upon age, as shown in the following graph which shows age plotted on a logarithmic scale in months.
- For a child aged 20 months, the dosing suggested for children with normal renal function aged 2 years or greater should be multiplied by about 0.97; the initial starting dose would be (30 × 0.97) = 29.1 mg/m2, administered orally three times daily. For a child aged 1 month, the starting dose should be multiplied by 0.68; the initial starting dose would be (30 × 0.68) = 20 mg/m2, administered orally three times daily. For a child aged 1 week, the initial starting oral dose should be multiplied by 0.3; the starting dose would be (30 × 0.3) = 9 mg/m2. Similar calculations should be made for increased doses as titration proceeds. Since the half-life of sotalol decreases with decreasing age (below about 2 years), time to steady-state will also increase. Thus, in neonates the time to steady-state may be as long as a week or longer.
- In all children, individualization of dosage is required. As in adults sotalol should be used with particular caution in children if the QTc is greater than 500 ms on therapy and serious consideration should be given to reducing the dose or discontinuing therapy when QTc exceeds 550 ms.
- The use of oral sotalol in children with renal impairment has not been investigated. Sotalol elimination is predominantly via the kidney in the unchanged form. Use of sotalol in any age group with decreased renal function should be at lower doses or at increased intervals between doses. Monitoring of heart rate and QTc is most important. It will take much longer to reach steady-state with any dose and/or frequency of administration in these children.
- Sinus bradycardia.
- Second degree AV block and third degree AV block, unless a functioning pacemaker is present.
- Congenital or acquired long QT syndromes.
- Cardiogenic shock.
- Uncontrolled congestive heart failure.
- Hypersensitivity to Betapace.
- Sotalol (AF) can cause serious ventricular arrhythmias, primarily Torsade de Pointes (TdP) type ventricular tachycardia, a polymorphic ventricular tachycardia associated with QT interval prolongation. QT interval prolongation is directly related to the dose of sotalol (AF). Factors such as reduced creatinine clearance, gender (female) and larger doses increase the risk of TdP. The risk of TdP can be reduced by adjustment of the sotalol (AF) dose according to creatinine clearance and by monitoring the ECG for excessive increases in the QT interval.
- Treatment with sotalol (AF) must therefore be started only in patients observed for a minimum of three days on their maintenance dose in a facility that can provide electrocardiographic monitoring and in the presence of personnel trained in the management of serious ventricular arrhythmias. Calculation of the creatinine clearance must precede administration of the first dose of sotalol (AF). For detailed instructions regarding dose selection.
- In eight controlled trials of patients with AFIB/AFL and other supraventricular arrhythmias (N=659) there were four cases of Torsade de Pointes reported (0.6%) during the controlled phase of treatment with sotalol (AF). The incidence of Torsade de Pointes was significantly lower in those patients receiving total daily doses of 320 mg or less (0.3%), as summarized in Table 5 below. Both patients who had Torsade de Pointes in the group receiving >320 mg/day were receiving 640 mg/day. In the group receiving ≤320 mg daily, one case of TdP occurred at a daily dose of 320 mg on day 4 of treatment and one case occurred on a daily dose of 160 mg on day 1 of treatment.
- The table below relates the incidence of Torsade de Pointes to on-therapy QTc and change in QTc from baseline. It should be noted, however, that the highest on therapy QTc was in many cases the one obtained at the time of the Torsade de Pointes event, so that the table overstates the predictive value of a high QTc.
- In addition to dose and presence of sustained VT, other risk factors for Torsade de Pointes were gender (females had a higher incidence), excessive prolongation of the QTc interval and history of cardiomegaly or congestive heart failure. Patients with sustained ventricular tachycardia and a history of congestive heart failure appear to have the highest risk for serious proarrhythmia (7%). Of the ventricular arrhythmia patients experiencing Torsade de Pointes, approximately two-thirds spontaneously reverted to their baseline rhythm. The others were either converted electrically (D/C cardioversion or overdrive pacing) or treated with other drugs. It is not possible to determine whether some sudden deaths represented episodes of Torsade de Pointes, but in some instances sudden death did follow a documented episode of Torsade de Pointes. Although sotalol therapy was discontinued in most patients experiencing Torsade de Pointes, 17% were continued on a lower dose.
- The use of sotalo (AF) in conjunction with other drugs that prolong the QT interval has not been studied and is not recommended. Such drugs include many antiarrhythmics, some phenothiazines, bepridil, tricyclic antidepressants, and certain oral macrolides. Class I or Class III antiarrhythmic agents should be withheld for at least three half-lives prior to dosing with sotalol (AF). In clinical trials, sotalots (AF) was not administered to patients previously treated with oral amiodarone for >1 month in the previous three months. Class Ia antiarrhythmic drugs, such as disopyramide, quinidine and procainamide and other Class III drugs (e.g., amiodarone) are not recommended as concomitant therapy with sotalots (AF), because of their potential to prolong refractoriness. There is only limited experience with the concomitant use of Class Ib or Ic antiarrhythmics.
- Sympathetic stimulation is necessary in supporting circulatory function in congestive heart failure, and beta-blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure. In patients who have heart failure controlled by digitalis and/or diuretics, sotalol (AF) should be administered cautiously. Both digitalis and sotalol slow AV conduction. As with all beta-blockers, caution is advised when initiating therapy in patients with any evidence of left ventricular dysfunction. In a pooled data base of four placebo-controlled AFIB/AFL and PSVT studies, new or worsening CHF occurred during therapy with sotalol (AF) in 5 (1.2%) of 415 patients. In these studies patients with uncontrolled heart failure were excluded (i.e., NYHA Functional Classes III or IV). In other premarketing sotalol studies, new or worsened congestive heart failure (CHF) occurred in 3.3% (n=3257) of patients and led to discontinuation in approximately 1% of patients receiving sotalol. The incidence was higher in patients presenting with sustained ventricular tachycardia/ventricular fibrillation (4.6%, n=1363), or a prior history of heart failure (7.3%, n=696). Based on a life-table analysis, the one-year incidence of new or worsened CHF was 3% in patients without a prior history and 10% in patients with a prior history of CHF. NYHA Classification was also closely associated to the incidence of new or worsened heart failure while receiving sotalol (1.8% in 1395 Class I patients, 4.9% in 1254 Class II patients and 6.1% in 278 Class III or IV patients).
- Sotalol (AF) should not be used in patients with hypokalemia or hypomagnesemia prior to correction of imbalance, as these conditions can exaggerate the degree of QT prolongation, and increase the potential for Torsade de Pointes. Special attention should be given to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or patients receiving concomitant diuretic drugs.
- The incidence of bradycardia (as determined by the investigators) in the supraventricular arrhythmia population treated with sotalol (AF) (N = 415) was 13%, and led to discontinuation in 2.4% of patients. Bradycardia itself increases the risk of Torsade de Pointes.
- Sotalol has been used in a controlled trial following an acute myocardial infarction without evidence of increased mortality (see Safety in Patients with Structural Heart Disease). Although specific studies of its use in treating atrial arrhythmias after infarction have not been conducted, the usual precautions regarding heart failure, avoidance of hypokalemia, bradycardia or prolonged QT interval apply.
- Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy. Occasional cases of exacerbation of angina pectoris, arrhythmias and, in some cases, myocardial infarction have been reported after abrupt discontinuation of beta-blocker therapy. Therefore, it is prudent when discontinuing chronically administered sotalol (AF), particularly in patients with ischemic heart disease, to carefully monitor the patient and consider the temporary use of an alternate beta-blocker if appropriate. If possible, the dosage of sotalol (AF) should be gradually reduced over a period of one to two weeks. If angina or acute coronary insufficiency develops, appropriate therapy should be instituted promptly. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized in patients receiving sotalols (AF), abrupt discontinuation in patients with arrhythmias may unmask latent coronary insufficiency.
- PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD IN GENERAL NOT RECEIVE BETA-BLOCKERS. It is prudent, if sotalol hydrochloride (AF) is to be administered, to use the smallest effective dose, so that inhibition of bronchodilation produced by endogenous or exogenous catecholamine stimulation of beta2 receptors may be minimized.
- While taking beta-blockers, patients with a history of anaphylactic reaction to a variety of allergens may have a more severe reaction on repeated challenge, either accidental, diagnostic or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat the allergic reaction.
- Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.
- In patients with diabetes (especially labile diabetes) or with a history of episodes of spontaneous hypoglycemia, sotalol (AF) should be given with caution since beta-blockade may mask some important premonitory signs of acute hypoglycemia; e.g., tachycardia.
- Sotalol (AF) should be used only with extreme caution in patients with sick sinus syndrome associated with symptomatic arrhythmias, because it may cause sinus bradycardia, sinus pauses or sinus arrest. In patients with AFIB and sinus node dysfunction, the risk of Torsade de Pointes with sotalol (AF) therapy is increased, especially after cardioversion. Bradycardia following cardioversion in these patients is associated with QTc interval prolongation which is augmented due to the reverse use dependence of the Class III effects of sotalol (AF). Patients with AFIB/AFL associated with the sick sinus syndrome may be treated with sotalol (AF) if they have an implanted pacemaker for control of bradycardia symptoms.
- Beta-blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-blockade which might be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm. The beta-blocking effects of sotalol (AF) may be useful in controlling heart rate in AFIB associated with thyrotoxicosis but no study has been conducted to evaluate this.
- In a pooled clinical trial population consisting of four placebo-controlled studies with 275 patients with AFIB/AFL treated with 160 to 320 mg doses of sotalol hydrochloride (AF), the following adverse events were reported at a rate of 2% or more in the 160-240 mg treated patients and greater than the rate in placebo patients (See Table 8). The data are presented by incidence of events in the sotalol (AF) and placebo groups by body system and daily dose. No significant irreversible non-cardiac end-organ toxicity was observed.
- Overall, discontinuation because of unacceptable adverse events was necessary in 17% of the patients, and occurred in 10% of patients less than two weeks after starting treatment. The most common adverse events leading to discontinuation of sotalol hydrochloride (AF) were: fatigue 4.6%, bradycardia 2.4%, proarrhythmia 2.2%, dyspnea 2%, and QT interval prolongation 1.4%.
- In clinical trials involving 1292 patients with sustained VT/VF, the common adverse events (occurring in ≥2% of patients) were similar to those described for the AFIB/AFL population.
- Occasional reports of elevated serum liver enzymes have occurred with sotalol therapy but no cause and effect relationship has been established. One case of peripheral neuropathy which resolved on discontinuation of sotalol and recurred when the patient was rechallenged with the drug was reported in an early dose tolerance study. Elevated blood glucose levels and increased insulin requirements can occur in diabetic patients.
- In an unblinded multicenter trial of 25 patients with SVT and/or VT receiving daily doses of 30, 90 and 210 mg/m2 with dosing every 8 hours for a total of 9 doses, no Torsades de Pointes or other serious new arrhythmias were observed. One (1) patient, receiving 30 mg/m2 daily, was discontinued because of increased frequency of sinus pauses/bradycardia. Additional cardiovascular AEs were seen at the 90 and 210 mg/m2 daily dose levels. They included QT prolongations (2 patients), sinus pauses/bradycardia (1 patient), increased severity of atrial flutter and reported chest pain (1 patient). Values for QTc ≥525 msec were seen in 2 patients at the 210 mg/m2 daily dose level. Serious adverse events including death, Torsades de Pointes, other proarrhythmias, high-degree AV blocks and bradycardia have been reported in infants and/or children.
- Foreign marketing experience with sotalol hydrochloride shows an adverse experience profile similar to that described above from clinical trials. Voluntary reports since introduction also include rare reports of: emotional liability, slightly clouded sensorium, incoordination, vertigo, paralysis, thrombocytopenia, eosinophilia, leukopenia, photosensitivity reaction, fever, pulmonary edema, hyperlipidemia, myalgia, pruritis, alopecia.
- The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been associated with sotalol (AF) during investigational use and foreign marketing experience.
- Digoxin: Proarrhythmic events were more common in sotalol treated patients also receiving digoxin; it is not clear whether this represents an interaction or is related to the presence of CHF, a known risk factor for proarrhythmia, in the patients receiving digoxin. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.
- Calcium blocking drugs: Sotalol (AF) should be administered with caution in conjunction with calcium blocking drugs because of possible additive effects on atrioventricular conduction or ventricular function. Additionally, concomitant use of these drugs may have additive effects on blood pressure, possibly leading to hypotension.
- Catecholamine-depleting agents: Concomitant use of catecholamine-depleting drugs, such as reserpine and guanethidine, with a beta-blocker may produce an excessive reduction of resting sympathetic nervous tone. Patients treated with sotalol (AF) plus a catecholamine depletor should therefore be closely monitored for evidence of hypotension and/or marked bradycardia which may produce syncope.
- Insulin and oral antidiabetics: Hyperglycemia may occur, and the dosage of insulin or antidiabetic drugs may require adjustment. Symptoms of hypoglycemia may be masked.
- Beta-2-receptor stimulants: Beta-agonists such as salbutamol, terbutaline and isoprenaline may have to be administered in increased dosages when used concomitantly with sotalol (AF).
- Clonidine: Beta-blocking drugs may potentiate the rebound hypertension sometimes observed after discontinuation of clonidine; therefore, caution is advised when discontinuing clonidine in patients receiving sotalol (AF).
- Other: No pharmacokinetic interactions were observed with hydrochlorothiazide or warfarin.
- Antacids: Administration of sotalol (AF) within 2 hours of antacids containing aluminum oxide and magnesium hydroxide should be avoided because it may result in a reduction in Cmax and AUC of 26% and 20%, respectively and consequently in a 25% reduction in the bradycardic effect at rest. Administration of the antacid two hours after sotalol (AF) has no effect on the pharmacokinetics or pharmacodynamics of sotalol.
- Drug/Laboratory Test Interactions: The presence of sotalol in the urine may result in falsely elevated levels of urinary metanephrine when measured by fluorimetric or photometric methods. In screening patients suspected of having a pheochromocytoma and being treated with sotalol, a specific method, such as a high performance liquid chromatographic assay with solid phase extraction (e.g., J. Chromatogr. 385:241, 1987) should be employed in determining levels of catecholamines.
- Although there are no adequate and well-controlled studies in pregnant women, sotalol HCl has been shown to cross the placenta, and is found in amniotic fluid. There has been a report of subnormal birth weight with sotalol. Therefore, sotalol (AF) should be used during pregnancy only if the potential benefit outweighs the potential risk.
- Administer the appropriate daily dose of sotalol hydrochloride tablets (AF) and begin continuous ECG monitoring with QT interval measurements 2 to 4 hours after each dose.
- The most common signs to be expected are bradycardia, congestive heart failure, hypotension, bronchospasm and hypoglycemia. In cases of massive intentional overdosage (2 to 16 grams) of sotalol the following clinical findings were seen: hypotension, bradycardia, cardiac asystole, prolongation of QT interval, Torsade de Pointes, ventricular tachycardia, and premature ventricular complexes. If overdosage occurs, therapy with sotalol (AF) should be discontinued and the patient observed closely. Because of the lack of protein binding, hemodialysis is useful for reducing sotalol plasma concentrations. Patients should be carefully observed until QT intervals are normalized and the heart rate returns to levels >50 bpm. The occurrence of hypotension following an overdose may be associated with an initial slow drug elimination phase (half life of 30 hours) thought to be due to a temporary reduction of renal function caused by the hypotension. In addition, if required, the following therapeutic measures are suggested:
- Bradycardia or Cardiac Asystole: Atropine, another anticholinergic drug, a beta-agonist or transvenous cardiac pacing.
- Heart Block: Second degree AV block and third degree AV block transvenous cardiac pacemaker.
- Hypotension: (depending on associated factors) epinephrine rather than isoproterenol or norepinephrine may be useful.
- Bronchospasm: Aminophylline or aerosol beta2-stimulant.
- Torsade de Pointes: DC cardioversion, transvenous cardiac pacing, epinephrine, magnesium sulfate.
- In children, a Class III electrophysiologic effect can be seen at daily doses of 210 mg/m2 body surface area (BSA). A reduction of the resting heart rate due to the beta-blocking effect of sotalol is observed at daily doses ≥ 90 mg/m2 in children.
- Satolol tablets contain the following inactive ingredients: microcrystalline cellulose, lactose, starch, stearic acid, magnesium stearate, colloidal silicon dioxide, and FD&C blue color #2 (aluminum lake, conc.).
- In man, the Class II (beta-blockade) electrophysiological effects of sotalol are manifested by increased sinus cycle length (slowed heart rate]), decreased AV nodal conduction and increased AV nodal refractoriness. The Class III electrophysiological effects in man include prolongation of the atrial and ventricular monophasic action potentials, and effective refractory period prolongation of atrial muscle, ventricular muscle, and atrio-ventricular accessory pathways (where present) in both the anterograde and retrograde directions. With oral doses of 160 to 640 mg/day, the surface ECG shows dose-related mean increases of 40-100 msec in QT and 10-40 msec in QTc. No significant alteration in QRS interval is observed.
- In a small study (n=25) of patients with implanted defibrillators treated concurrently with sotalol, the average defibrillatory threshold was 6 joules (range 2-15 joules) compared to a mean of 16 joules for a nonrandomized comparative group primarily receiving amiodarone.
- Twenty-five children in an unblinded, multicenter trial with supraventricular tachycardias (SVT) and/or ventricular tachyarrhythmias (VT), aged between 3 days and 12 years (mostly neonates and infants), received an ascending titration regimen with daily doses of 30, 90 and 210 mg/m2 with dosing every 8 hours for a total 9 doses. During steady-state, the respective average increases above baseline of the QTc interval, in msec (%), were 2(+1%), 14(+4%) and 29(+7%) msec at the 3 dose levels. The respective mean maximum increases above baseline of the QTc interval, in msec (%), were 23(+6%), 36(+9%) and 55(+14%) msec at the 3 dose levels. The steadystate percent increases in the RR interval were 3, 9 and 12%. The smallest children (BSA<0.33m2) showed a tendency for larger Class III effects (ΔQTc) and an increased frequency of prolongations of the QTc interval as compared with larger children (BSA≥0.33m2). The beta-blocking effects also tended to be greater in the smaller children (BSA<0.33m2). Both the Class III and beta-blocking effects of sotalol were linearly related with the plasma concentrations.
- Sotalol hydrochloride does not bind to plasma proteins and is not metabolized. Sotalol hydrochloride shows very little intersubject variability in plasma levels. The pharmacokinetics of the d and l enantiomers of sotalol are essentially identical. Sotalol hydrochloride crosses the blood brain barrier poorly. Excretion is predominantly via the kidney in the unchanged form, and therefore lower doses are necessary in conditions of renal impairment. Age per se does not significantly alter the pharmacokinetics of sotalol, but impaired renal function in geriatric patients can increase the terminal elimination half-life, resulting in increased drug accumulation. The absorption of sotalol hydrochloride was reduced by approximately 20% compared to fasting when it was administered with a standard meal. Since sotalol hydrochloride is not subject to first-pass metabolism, patients with hepatic impairment show no alteration in clearance of sotalol.
- The combined analysis of two unblinded, multicenter trials (a single dose and a multiple dose study) with 59 children, aged between 3 days and 12 years, showed the pharmacokinetics of sotalol to be first order. A daily dose of 30 mg/m2 of sotalol was administered in the single dose study and daily doses of 30, 90 and 210 mg/m2 were administered q 8h in the multi-dose study. After rapid absorption with peak levels occurring on average between 2-3 hours following administration, sotalol was eliminated with a mean half life of 9.5 hours. Steady-state was reached after 1-2 days. The average peak to trough concentration ratio was 2. BSA was the most important covariate and more relevant than age for the pharmacokinetics of sotalol.The smallest children (BSA<0.33m2) exhibited a greater drug exposure (+59%) than the larger children who showed a uniform drug concentration profile. The intersubject variation for oral clearance was 22%.
- Sotalol has not been evaluated in any specific assay of mutagenicity or clastogenicity.
- No significant reduction in fertility occurred in rats at oral doses of 1000 mg/kg/ day (approximately 100 times the MRHD as mg/kg or 9 times the MRHD as mg/m2) prior to mating, except for a small reduction in the number of offspring per litter.
- Sotalol hydrochloride (AF) has been studied in patients with symptomatic AFIB/AFL in two principal studies, one in patients with primarily paroxysmal AFIB/AFL, the other in patients with primarily chronic AFIB.
- In one study, a U.S. multicenter, randomized, placebo-controlled, double-blind, dose-response trial of patients with symptomatic primarily paroxysmal AFIB/AFL, three fixed dose levels of sotalol hydrochloride (AF) (80 mg, 120 mg and 160 mg) twice daily and placebo were compared in 253 patients. In patients with reduced creatinine clearance (40-60 mL/min) the same doses were given once daily. Patients were not randomized for the following reasons: QT >450 msec; creatinine clearance <40 mL/min; intolerance to beta-blockers; bradycardia-tachycardia syndrome in the absence of an implanted pacemaker; AFIB/AFL was asymptomatic or was associated with syncope, embolic CVA or TIA; acute myocardial infarction within the previous 2 months; congestive heart failure; bronchial asthma or other contraindications to beta-blocker therapy; receiving potassium losing diuretics without potassium replacement or without concurrent use of ACE-inhibitors; uncorrected hypokalemia (serum potassium <3.5 meq/L) or hypomagnesemia (serum magnesium <1.5 meq/L); received chronic oral amiodarone therapy for >1 month within previous 12 weeks; congenital or acquired long QT syndromes; history of Torsade de Pointes with other antiarrhythmic agents which increase the duration of ventricular repolarization; sinus rate <50 bpm during waking hours; unstable angina pectoris; receiving treatment with other drugs that prolong the QT interval; and AFIB/AFL associated with the Wolff-Parkinson-White syndrome (WPW). If the QT interval increased to ≥520 msec (or JT ≥430 msec if QRS >100 msec) the drug was discontinued. The patient population in this trial was 64% male, and the mean age was 62 years. No structural heart disease was present in 43% of the patients. Doses were administered once daily in 20% of the patients because of reduced creatinine clearance.
- Sotalol hydrochloride (AF) was shown to prolong the time to the first symptomatic, ECG documented recurrence of AFIB/AFL, as well as to reduce the risk of such recurrence at both 6 and 12 months. The 120 mg dose was more effective than 80 mg, but 160 mg did not appear to have an added benefit. Note that these doses were given twice or once daily, depending on renal function. The results are shown in the figure and tables below.
Please note that columns do not add up to 100% due to discontinuations (D/C) for "other" reasons.
Discontinuation because of adverse events was dose related.
- In a second multicenter, randomized, placebo-controlled, double-blind study of 6 months duration in 232 patients with chronic AFIB, sotalol hydrochloride (AF) was titrated over a dose range from 80 mg/day to 320 mg/day. The patient population of this trial was 70% male with a mean age of 65 years. Structural heart disease was present in 49% of the patients. All patients had chronic AFIB for >2 weeks but <1 year at entry with a mean duration of 4.1 months. Patients were excluded if they had significant electrolyte imbalance, QTc >460 msec, QRS >140 msec, any degree of AV block or functioning pacemaker, uncompensated cardiac failure, asthma, significant renal disease (estimated creatinine clearance <50 mL/min), heart rate <50 bpm, myocardial infarction or open heart surgery in past 2 months, unstable angina, infective endocarditis, active pericarditis or myocarditis, ≥ 3 DC cardioversions in the past, medications that prolonged QT interval, and previous amiodarone treatment. After successful cardioversion patients were randomized to receive placebo (n=114) or sotalol hydrochloride (AF) (n=118), at a starting dose of 80 mg twice daily. If the initial dose was not tolerated it was decreased to 80 mg once daily, but if it was tolerated it was increased to 160 mg twice daily. During the maintenance period 67% of treated patients received a dose of 160 mg twice daily, and the remainder received doses of 80 mg once daily (17%) and 80 mg twice daily (16%).
- The figure and Tables below show the results of the trial. There was a longer time to ECG-documented recurrence of AFIB and a reduced risk of recurrence at 6 months compared to placebo.
- In a multicenter double-blind randomized study reported by D. Julian et al, the effect of sotalol 320 mg once daily was compared with that of placebo in 1456 patients (randomized 3:2, sotalol to placebo) surviving an acute myocardial infarction (MI). Treatment was started 5 to 14 days after infarction. Patients were followed for 12 months. The mortality rate was 7.3% in the sotalol group and 8.9% in the placebo group, not a statistically significant difference. Although the results do not show evidence of a benefit of sotalol in this population, they do not show an added risk in post MI patients receiving sotalol.
- Betapace (sotalol hydrochloride); capsule-shaped light-blue scored tablets imprinted with the strength and “Betapace”, are available as follows:
- 80 mg strength, bottle of 100 (NDC 50419-105-10)
- 120 mg strength, bottle of 100 (NDC 50419-109-10)
- 160 mg strength, bottle of 100 (NDC 50419-106-10)
- Intravenous sotalol is supplied in 10 mL vials, each containing 150 mg sotalol hydrochloride (15 mg/mL).
- Each vial is individually packed in a carton (NDC 67457-176-10).
- Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).
- Store at 25°C (77°F) with excursions permitted to 15°-30° C (59°-86°F).
- Protect from freezing and light
Medications and Supplements
- Assessment of patients' medication history should include all over-counter, prescription and herbal/natural preparations with emphasis on preparations that may affect the pharmacodynamics of sotalol (AF) such as other cardiac antiarrhythmic drugs, some phenothiazines, bepridil, tricyclic antidepressants and oral macrolides. Patients should be instructed to notify their health care providers of any change in over-the-counter, prescription or supplement use. If a patient is hospitalized or is prescribed a new medication for any condition, the patient must inform the health care provider of ongoing sotalol (AF) therapy. Patients should also check with their health care provider and/or pharmacist prior to taking a new over-the-counter medicine.
Electrolyte Imbalance
- If patients experience symptoms that may be associated with electrolyte disturbances, such as excessive or prolonged diarrhea, sweating, or vomiting, or loss of appetite or thirst, these conditions should be immediately reported to their health care provider.
Dosing Schedule
- Patients should be instructed NOT to double the next dose if a dose is missed. The next dose should be taken at the usual time.
- Betapace AF
- Sorine
- ↑ Gooding PG, Berman E (1974). "An evaluation of sotalol, a beta-blocking agent, in patients with angina pectoris". Postgrad Med J. 50 (590): 734–6. PMC 2496011. PMID 4157126.CS1 maint: PMC format (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Areskog NH, Cullhed I, Ringqvist I, Ström G (1975). "Cardiovascular and respiratory effects of the beta-adrenoceptive antagonist sotalol: studies in health, angina pectoris and obstructive lung disease". Eur J Clin Pharmacol. 8 (6): 403–8. PMID 1233240.CS1 maint: Multiple names: authors list (link)
- ↑ Parvinen I, Paukkala E (1979). "Thrice-daily blood pressure readings on sotalol in the treatment of hypertension: once- versus twice-daily regimen". J Clin Pharmacol. 19 (8-9 Pt 2): 533–9. PMID 489772. | https://www.wikidoc.org/index.php/Sotalol | |
a059cd09d4469f5fd9251228e44420f51abb316e | wikidoc | Soteria | Soteria
# Overview
The Soteria model is milieu-therapeutic recovery method, characterized by its founder as "the 24 hour a day application of interpersonal phenomenologic interventions by a nonprofessional staff, usually without neuroleptic drug treatment, in the context of a small, homelike, quiet, supportive, protective, and tolerant social environment." More recent adaptions of this model sometimes employ professional staff. It has traditionally been applied to the treatment of those given a diagnosis of schizophrenia. The houses Soteria patients are admitted to are called Soteria houses.
Soteria houses are often seen as alternatives to a psychiatric hospital system perceived as authoritarian, hostile/violent and based on a routine use of psychiatric (particularly antipsychotic) drugs. Soteria houses are sometimes viewed as early intervention or crisis resolution services based on a supportive recovery model.
# History
The original Soteria Research Project was founded near San Francisco between 1969 and 1971 by psychiatrist Loren Mosher, who was influenced by the philosophy of moral treatment, previous experimental therapeutic communities (such as the Fairweather Lodges), the work of Harry Stack Sullivan, and Freudian psychoanalysis. The name Soteria comes from the Greek for "salvation" or "deliverance" (see Soter).
Mosher's first Soteria house specifically selected unmarried subjects between the ages of 18 and 30 who had recently been diagnosed as meeting the DSM-II criteria for schizophrenia. Staff members at the house were encouraged to treat residents as peers and to share household chores. The program was designed to create a quiet, calming environment that respected and tolerated individual differences and autonomy. There was also an ethos of shared responsibility for the running of the house and playing a part in a mutually-supportive community, with the distinction between experts and non-experts downplayed (similar to therapeutic communities). Psychotropic medication, including anti-psychotics, were not completely rejected and were used in some circumstances.
The Soteria project was admired by many professionals around the world who aspired to create mental health services based on a social, as opposed to a medical, model of mental health. It was also heavily criticised as irresponsible or ineffective. The US Soteria Project closed as a clinical program in 1983 due to lack of financial support, although it became the subject of research evaluation with competing claims and analyses. Second generation US successors to the original Soteria house (called Crossing Place and McAuliffe House) also closed around that time.
A first European near-replication of the original Soteria approach was implemented in 1984 in Berne, Switzerland, on a somewhat different conceptual basis. Three Soteria-like environments focused on longer term rehabilitation were created in Sweden (Perris, 1989).
# Current Soteria work
Soteria or Soteria-based houses are currently run in Sweden, Finland, Germany, Switzerland, Hungary and some other countries. | Soteria
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
The Soteria model is milieu-therapeutic recovery method, characterized by its founder as "the 24 hour a day application of interpersonal phenomenologic interventions by a nonprofessional staff, usually without neuroleptic drug treatment, in the context of a small, homelike, quiet, supportive, protective, and tolerant social environment."[1] More recent adaptions of this model sometimes employ professional staff.[2] It has traditionally been applied to the treatment of those given a diagnosis of schizophrenia. The houses Soteria patients are admitted to are called Soteria houses.
Soteria houses are often seen as alternatives to a psychiatric hospital system perceived as authoritarian, hostile/violent and based on a routine use of psychiatric (particularly antipsychotic) drugs. Soteria houses are sometimes viewed as early intervention or crisis resolution services based on a supportive recovery model.
# History
The original Soteria Research Project was founded near San Francisco between 1969 and 1971 by psychiatrist Loren Mosher, who was influenced by the philosophy of moral treatment, previous experimental therapeutic communities (such as the Fairweather Lodges), the work[3] of Harry Stack Sullivan, and Freudian psychoanalysis. The name Soteria comes from the Greek for "salvation" or "deliverance" (see Soter).[1]
Mosher's first Soteria house specifically selected unmarried subjects between the ages of 18 and 30 who had recently been diagnosed as meeting the DSM-II criteria for schizophrenia. Staff members at the house were encouraged to treat residents as peers and to share household chores. The program was designed to create a quiet, calming environment that respected and tolerated individual differences and autonomy. There was also an ethos of shared responsibility for the running of the house and playing a part in a mutually-supportive community, with the distinction between experts and non-experts downplayed (similar to therapeutic communities). Psychotropic medication, including anti-psychotics, were not completely rejected and were used in some circumstances.
The Soteria project was admired by many professionals around the world who aspired to create mental health services based on a social, as opposed to a medical, model of mental health. It was also heavily criticised as irresponsible or ineffective. The US Soteria Project closed as a clinical program in 1983 due to lack of financial support, although it became the subject of research evaluation with competing claims and analyses. Second generation US successors to the original Soteria house (called Crossing Place and McAuliffe House) also closed around that time.
A first European near-replication of the original Soteria approach was implemented in 1984 in Berne, Switzerland, on a somewhat different conceptual basis. Three Soteria-like environments focused on longer term rehabilitation were created in Sweden (Perris, 1989).
# Current Soteria work
Soteria or Soteria-based houses are currently run in Sweden,[4] Finland,[citation needed] Germany,[5][6][7] Switzerland,[8] Hungary[9] and some other countries. | https://www.wikidoc.org/index.php/Soteria | |
7b080c8d9a9e5b7ca7bf70d19cc8eaaf10eb5c4c | wikidoc | Souroti | Souroti
Souroti (Greek: Σουρωτή), a rural village in the Thessaloniki prefecture of Greece is located 25 kilometers (16 miles) outside of the city of Thessaloniki. In Greece the village is particularly known for the mineral water bottled there. Administratively it belongs to the municipality of Vasilika.
# History
Souroti is an immigrant's village, one of the many that were established in Greek Macedonia after the Balkan wars and the population exchange between Greece and Turkey. Shortly before 1912 the area was called "Surukli" (from the Turkish suru which means heard) and was owned by five Turkish land owners (Τσιφλικάδες) who sold their land to Jews from Thessaloniki. The first Greeks that settled in the area were a vlach family from Vlasti of the Kozani prefecture, the Christos Lolas' family. Although they were originally shepherds, the family sold their sheep to buy the land from the Jews. In 1914 forty families of arvanites came from Mandritsa (Μανδρίτσα) in North Thrace following a Bulgarian invasion in their home village. Most of them were bilingual in Greek and Arvanitika. Their primary occupation was silk production and they moved to Souroti to take advantage of the local mulberries. In 1922, after the population exchange between Greece and Turkey about 48 families arrived from Asia Minor originating from Izmir (Σμύρνη), Aydin (Αηδίνι), Boursa (Προύσσα), Kyos (Κύος), Mudanya (Μουδανιά) and also from Eastern Thrace. Those were educated and they carried their own traditions. In Souroti they worked as silk, olive oil producers and vine dressers. Between 1928 and 1930 more vlach shepherds came from Vlasti along with 4-5 families of Sarakatsanoi (Σαρακατσάνοι). Land was distributed to the immigrants by the Greek state first in 1914 and later in 1932.
## Modern Establishment
The community of Souroti was officially established and recognized by the Greek state on Sep. 20th, 1947. Since then the village, whose main productive activities were agriculture and bottling of mineral water, has undergone steady development. In 1997 during a major reorganization of local self-govenrment initiated by the Greek government called "Kapodistrias plan", Souroti merged with the municipality of Vasilika along with Ag. Paraskeyi, Ag. Antonio, Libadi, Monopigado and Peristera. Nowadays people from the nearby Thessaloniki are moving to the area around the village which is expected to turn into a suburb of Thessaloniki.
# Discovery of the mineral water spring
While still part of the Ottoman Empire, the area around today's bottling factory was a swamp, and the spring of mineral water unknown. During the 1915 military campaigns of the First World War, the French troops that camped at the then called Surukli mapped the spring and built a rudimentary bottling facility. In 1917 Serbian troops camped there and they too built a new bottling facility. They called the water "Sour Water" (Serbian: Kisela Voda, Template:Lang-el). The Lolas family appropriated and refurbished the facility in 1918. In 1925 George Chonaios took over the Lola's enterprise. Chonaios had the facility work as a private enterprise, however he allotted 5% of the profit to the local community. In 1998 the company went public. Since then it exhibited rapid development and became one of the most popular mineral water brands in Greece.
## Quality of the mineral water
Souroti water has been recognized as a sub-acidic sparkling mineral water rich in calcium and magnesium in accordance with Greek Legislation (Government Gazette 600/1-8-1991, Decision No. 4). It is also included in the European Union's list of Natural Mineral Waters. The water, at least in the beginning of 20th century was naturally sparkling. Although it still preserves its original mineral composition, nowadays carbon dioxide is added during bottling.
The water is estimated to come from a container approximately 150 m underground. It owes its excellent quality to the rock formations at Mount Anthemounta which consist of semi-metamorphic, metamorphic and igneous rocks. Water flowing in the substrate is slow-moving and as it passes through the various rocks it is filtered and enriched with beneficial elements giving it its unique mineral composition and distinctive taste. Water in the spring is cold at a steady temperature of around 16 °C. Its special features are a high magnesium content with the ideal calcium to magnesium ratio and a low sodium and nitrate content. It also contains potassium and fluorine as well as valuable trace elements such as iron, copper, manganese, lithium, selenium, chromium and zinc. It has exceptional taste and is very pleasant to drink, assists in the functioning of the digestive and urinary systems and it has several other health benefits. One liter of Souroti water meets 1/4 of the body's daily needs in calcium and magnesium. All this make it different from soda water which is ordinary potable water to which sodium bicarbonate has been added so that it acquires approximately the same properties as natural mineral water.
# Notes
- Μαραβελάκη, Μ. (1993). Οι προσφυγικές εγκαταστάσεις στην περιοχή Θεσσαλονίκης (in Greek). Θεσσαλονίκη: Ανατύπωση Εκδόσεις Βάνιας. Unknown parameter |coauthors= ignored (help)CS1 maint: Unrecognized language (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | Souroti
Template:Infobox Greek Dimos
Souroti (Greek: Σουρωτή), a rural village in the Thessaloniki prefecture of Greece is located 25 kilometers (16 miles) outside of the city of Thessaloniki. In Greece the village is particularly known for the mineral water bottled there. Administratively it belongs to the municipality of Vasilika.
# History
Souroti is an immigrant's village, one of the many that were established in Greek Macedonia after the Balkan wars and the population exchange between Greece and Turkey. Shortly before 1912 the area was called "Surukli" (from the Turkish suru which means heard) and was owned by five Turkish land owners (Τσιφλικάδες) who sold their land to Jews from Thessaloniki. The first Greeks that settled in the area were a vlach family from Vlasti of the Kozani prefecture, the Christos Lolas' family. Although they were originally shepherds, the family sold their sheep to buy the land from the Jews. In 1914 forty families of arvanites came from Mandritsa (Μανδρίτσα) in North Thrace following a Bulgarian invasion in their home village. Most of them were bilingual in Greek and Arvanitika. Their primary occupation was silk production and they moved to Souroti to take advantage of the local mulberries. In 1922, after the population exchange between Greece and Turkey about 48 families arrived from Asia Minor originating from Izmir (Σμύρνη), Aydin (Αηδίνι), Boursa (Προύσσα), Kyos (Κύος), Mudanya (Μουδανιά) and also from Eastern Thrace. Those were educated and they carried their own traditions. In Souroti they worked as silk, olive oil producers and vine dressers. Between 1928 and 1930 more vlach shepherds came from Vlasti along with 4-5 families of Sarakatsanoi (Σαρακατσάνοι). Land was distributed to the immigrants by the Greek state first in 1914 and later in 1932.
## Modern Establishment
The community of Souroti was officially established and recognized by the Greek state on Sep. 20th, 1947. Since then the village, whose main productive activities were agriculture and bottling of mineral water, has undergone steady development. In 1997 during a major reorganization of local self-govenrment initiated by the Greek government called "Kapodistrias plan", Souroti merged with the municipality of Vasilika along with Ag. Paraskeyi, Ag. Antonio, Libadi, Monopigado and Peristera. Nowadays people from the nearby Thessaloniki are moving to the area around the village which is expected to turn into a suburb of Thessaloniki.
# Discovery of the mineral water spring
While still part of the Ottoman Empire, the area around today's bottling factory was a swamp, and the spring of mineral water unknown. During the 1915 military campaigns of the First World War, the French troops that camped at the then called Surukli mapped the spring and built a rudimentary bottling facility. In 1917 Serbian troops camped there and they too built a new bottling facility. They called the water "Sour Water" (Serbian: Kisela Voda, Template:Lang-el). The Lolas family appropriated and refurbished the facility in 1918. In 1925 George Chonaios took over the Lola's enterprise. Chonaios had the facility work as a private enterprise, however he allotted 5% of the profit to the local community. In 1998 the company went public. Since then it exhibited rapid development and became one of the most popular mineral water brands in Greece.
## Quality of the mineral water
Souroti water has been recognized as a sub-acidic sparkling mineral water rich in calcium and magnesium in accordance with Greek Legislation (Government Gazette 600/1-8-1991, Decision No. 4). It is also included in the European Union's list of Natural Mineral Waters. The water, at least in the beginning of 20th century was naturally sparkling. Although it still preserves its original mineral composition, nowadays carbon dioxide is added during bottling.
The water is estimated to come from a container approximately 150 m underground. It owes its excellent quality to the rock formations at Mount Anthemounta which consist of semi-metamorphic, metamorphic and igneous rocks. Water flowing in the substrate is slow-moving and as it passes through the various rocks it is filtered and enriched with beneficial elements giving it its unique mineral composition and distinctive taste. Water in the spring is cold at a steady temperature of around 16 °C. Its special features are a high magnesium content with the ideal calcium to magnesium ratio and a low sodium and nitrate content. It also contains potassium and fluorine as well as valuable trace elements such as iron, copper, manganese, lithium, selenium, chromium and zinc. It has exceptional taste and is very pleasant to drink, assists in the functioning of the digestive and urinary systems and it has several other health benefits. One liter of Souroti water meets 1/4 of the body's daily needs in calcium and magnesium. All this make it different from soda water which is ordinary potable water to which sodium bicarbonate has been added so that it acquires approximately the same properties as natural mineral water.
# Notes
- Μαραβελάκη, Μ. (1993). Οι προσφυγικές εγκαταστάσεις στην περιοχή Θεσσαλονίκης (in Greek). Θεσσαλονίκη: Ανατύπωση Εκδόσεις Βάνιας. Unknown parameter |coauthors= ignored (help)CS1 maint: Unrecognized language (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | https://www.wikidoc.org/index.php/Souroti | |
88cc0670239073a1282f17689b411b3bedd07156 | wikidoc | Spargel | Spargel
Spargel is the German name for asparagus. Most asparagus in Germany is white, as it is grown covered in soil (hilling) in order to prevent photosynthesis. This process prevents the asparagus from turning green and results in a sweeter and more tender taste. It is generally harvested from late April to early June. Some green asparagus is available in Germany, but would most likely be called grüner Spargel.
Spargel is very popular in Europe, especially Germany where it is known as "Königliches Gemüse" (Royal Vegetable). Germany produces 57,000 tons of asparagus a year, however that is only enough to meet 61% of its consumption demands. When spargel is harvested in the late spring, many German cities hold festivals in celebration. Schwetzingen claims to be the “Asparagus Capital of the World” and holds an annual Spargelfest (asparagus festival) in which it names a lucky person as Spargel Queen.
During Spargelsaison (asparagus season), which occurs during May, Spargel is sold at numerous roadside stands and in open air markets in every town in Germany. It is also a popular item at restaurants and fresh or frischer Spargel is advertised outside of many restaurants during Spargelsaison.
# Popular culture
- In the episode The 30% Iron Chef of Futurama, Bender's teacher's name is Helmut Spargle, a reference to the German vegetable. | Spargel
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Spargel is the German name for asparagus. Most asparagus in Germany is white, as it is grown covered in soil (hilling) in order to prevent photosynthesis. This process prevents the asparagus from turning green and results in a sweeter and more tender taste. It is generally harvested from late April to early June. Some green asparagus is available in Germany, but would most likely be called grüner Spargel.
Spargel is very popular in Europe, especially Germany where it is known as "Königliches Gemüse" (Royal Vegetable). Germany produces 57,000 tons of asparagus a year, however that is only enough to meet 61% of its consumption demands.[1] When spargel is harvested in the late spring, many German cities hold festivals in celebration. Schwetzingen claims to be the “Asparagus Capital of the World” and holds an annual Spargelfest (asparagus festival) in which it names a lucky person as Spargel Queen.
During Spargelsaison (asparagus season), which occurs during May, Spargel is sold at numerous roadside stands and in open air markets in every town in Germany. It is also a popular item at restaurants and fresh or frischer Spargel is advertised outside of many restaurants during Spargelsaison.
# Popular culture
- In the episode The 30% Iron Chef of Futurama, Bender's teacher's name is Helmut Spargle, a reference to the German vegetable. | https://www.wikidoc.org/index.php/Spargel | |
c3a8eab15129d19b523141eff1cc7a0520562ba5 | wikidoc | Stibine | Stibine
# Overview
Stibine is the chemical compound with the formula SbH3. This colourless gas is the principal covalent hydride of antimony and a heavy analogue of ammonia. The molecule is pyramidal with H–Sb–H angles of 91.7° and Sb–H distances of 1.707 Å (170.7 pm).
# Preparation and properties
SbH3 is generally prepared by the reaction of Sb3+ sources with H− equivalents:
Alternatively, sources of Sb3− react with protonic reagents (even water) to also produce this unstable gas:
The chemical properties of SbH3 resemble those for AsH3. Typical for a heavy hydride (e.g. AsH3, H2Te, SnH4), SbH3 is unstable with respect to its elements. The gas decomposes slowly at room temperature but rapidly at 200 °C:
The decomposition is autocatalytic and can be explosive.
SbH3 is readily oxidized by O2 or even air:
SbH3 exhibits no basicity, but it can be deprotonated:
# Uses
Stibine is used in the semiconductor industry to dope small quantities of antimony via the process of chemical vapour deposition (CVD). Reports claim the use of SbH3 as a fumigant but its instability and awkward preparation contrast with the more conventional fumigant PH3.
# History
As stibine (SbH3) is very similar to arsine (AsH3), it is also detected by the Marsh test. This sensitive test detects arsine generated in the presence of arsenic. This procedure, developed around 1836 by James Marsh, is based upon treating a sample with arsenic-free zinc and dilute sulfuric acid: if the sample contains arsenic, gaseous arsine will form. The gas is swept into a glass tube and decomposed by means of heating around 250–300 °C. The presence of arsenic is indicated by formation of a deposit in the heated part of the equipment. The formation of a black mirror deposit in the cool part of the equipment indicates the presence of antimony.
In 1837 Lewis Thomson and Pfaff independently discovered stibine. It took some time before the properties of the toxic case could be determined, partly because a suitable synthesis was not available. In 1876 Francis Jones tested several synthesis methods, but it was not before 1901 when Alfred Stock determined most of the properties of stibine.
# Safety
SbH3 is an unstable flammable gas. It is highly toxic, with an LC50 of 100 ppm in mice. Fortunately, SbH3 is so unstable that it is rarely encountered outside of laboratories.
# Toxicology
The toxicity of stibine is distinct from that of other antimony compounds, but similar to that of arsine. Stibine binds to the haemoglobin of red blood cells, causing them to be destroyed by the body. Most cases of stibine poisoning have been accompanied by arsine poisoning, although animal studies indicate that their toxicities are equivalent. The first signs of exposure, which can take several hours to become apparent, are headaches, vertigo and nausea, followed by the syptoms of hemolytic anemia (high levels of unconjugated bilirubin), hemoglobinuria and nephropathy. | Stibine
Template:Chembox new
# Overview
Stibine is the chemical compound with the formula SbH3. This colourless gas is the principal covalent hydride of antimony and a heavy analogue of ammonia. The molecule is pyramidal with H–Sb–H angles of 91.7° and Sb–H distances of 1.707 Å (170.7 pm).
# Preparation and properties
SbH3 is generally prepared by the reaction of Sb3+ sources with H− equivalents:[1]
Alternatively, sources of Sb3− react with protonic reagents (even water) to also produce this unstable gas:
The chemical properties of SbH3 resemble those for AsH3.[2] Typical for a heavy hydride (e.g. AsH3, H2Te, SnH4), SbH3 is unstable with respect to its elements. The gas decomposes slowly at room temperature but rapidly at 200 °C:
The decomposition is autocatalytic and can be explosive.
SbH3 is readily oxidized by O2 or even air:
SbH3 exhibits no basicity, but it can be deprotonated:
# Uses
Stibine is used in the semiconductor industry to dope small quantities of antimony via the process of chemical vapour deposition (CVD). Reports claim the use of SbH3 as a fumigant but its instability and awkward preparation contrast with the more conventional fumigant PH3.
# History
As stibine (SbH3) is very similar to arsine (AsH3), it is also detected by the Marsh test. This sensitive test detects arsine generated in the presence of arsenic.[2] This procedure, developed around 1836 by James Marsh, is based upon treating a sample with arsenic-free zinc and dilute sulfuric acid: if the sample contains arsenic, gaseous arsine will form. The gas is swept into a glass tube and decomposed by means of heating around 250–300 °C. The presence of arsenic is indicated by formation of a deposit in the heated part of the equipment. The formation of a black mirror deposit in the cool part of the equipment indicates the presence of antimony.
In 1837 Lewis Thomson and Pfaff independently discovered stibine. It took some time before the properties of the toxic case could be determined, partly because a suitable synthesis was not available. In 1876 Francis Jones tested several synthesis methods,[3] but it was not before 1901 when Alfred Stock determined most of the properties of stibine.[4][5]
# Safety
SbH3 is an unstable flammable gas. It is highly toxic, with an LC50 of 100 ppm in mice. Fortunately, SbH3 is so unstable that it is rarely encountered outside of laboratories.
# Toxicology
The toxicity of stibine is distinct from that of other antimony compounds, but similar to that of arsine.[6] Stibine binds to the haemoglobin of red blood cells, causing them to be destroyed by the body. Most cases of stibine poisoning have been accompanied by arsine poisoning, although animal studies indicate that their toxicities are equivalent. The first signs of exposure, which can take several hours to become apparent, are headaches, vertigo and nausea, followed by the syptoms of hemolytic anemia (high levels of unconjugated bilirubin), hemoglobinuria and nephropathy. | https://www.wikidoc.org/index.php/Stibine | |
fdab06891cd2846a5c2138d2b3c757c7e077c742 | wikidoc | Suction | Suction
Suction is the flow of a fluid into a partial vacuum, or region of low pressure. The pressure gradient between this region and the ambient pressure will propel matter toward the low pressure area. Suction is popularly thought of as an attractive effect, which is incorrect since vacuums do not innately attract matter. Dust being "sucked" into a vacuum cleaner is actually being pushed in by the higher pressure air on the outside of the cleaner.
The higher pressure of the surrounding fluid can push matter into a vacuum but a vacuum cannot attract matter.
# Suction in biology
Infants, and all baby mammals, are born with a sucking (or suckling) reflex, which they use in nursing liquid foods, such as milk. They do not have to learn this reflex, because it is instinctive. Some adult animals use suction in drinking, as do humans when using drinking straws. In breathing, the diaphragm muscle is used to expand the lungs, allowing air to enter due to the outside air pressure.
Large plants can actually create a negative pressure by transpirational pull.
# Pumps
Pumps used for pumping or moving fluids typically have an inlet where the fluid enters the pump and an outlet where the fluid comes out. The inlet location is said to be at the suction side of the pump. The outlet location is said to be at the discharge side of the pump. Operation of the pump creates suction (a lower pressure) at the suction side so that fluid can enter the pump through the inlet. Pump operation also causes higher pressure at the discharge side by forcing the fluid out at the outlet. There may be pressure sensing devices at the pump's suction and/or discharge sides which control the operation of the pump. For example, if the suction pressure of a centrifugal pump is too low, a device may trigger the pump to shut off to keep it from running dry; i. e. with no fluid entering.
Under normal conditions of atmospheric pressure suction can draw pure water up to a maximum height of approximately 10.3 m (33.9 feet or suction head). There is a theoretical limit of height that a perfect pump can raise water up a pipe and that is when the pump draws a perfect vacuum with no air in the suction pipe and atmospheric pressure of around 14 psi. In reality, no pumps are perfect. Leakage around the moving parts of the pump limit normal water pumps from starting if they lose prime. | Suction
Suction is the flow of a fluid into a partial vacuum, or region of low pressure. The pressure gradient between this region and the ambient pressure will propel matter toward the low pressure area. Suction is popularly thought of as an attractive effect, which is incorrect since vacuums do not innately attract matter. Dust being "sucked" into a vacuum cleaner is actually being pushed in by the higher pressure air on the outside of the cleaner.
The higher pressure of the surrounding fluid can push matter into a vacuum but a vacuum cannot attract matter.
# Suction in biology
Infants, and all baby mammals, are born with a sucking (or suckling) reflex, which they use in nursing liquid foods, such as milk. They do not have to learn this reflex, because it is instinctive. Some adult animals use suction in drinking, as do humans when using drinking straws. In breathing, the diaphragm muscle is used to expand the lungs, allowing air to enter due to the outside air pressure.
Large plants can actually create a negative pressure by transpirational pull.
# Pumps
Pumps used for pumping or moving fluids typically have an inlet where the fluid enters the pump and an outlet where the fluid comes out. The inlet location is said to be at the suction side of the pump. The outlet location is said to be at the discharge side of the pump. Operation of the pump creates suction (a lower pressure) at the suction side so that fluid can enter the pump through the inlet. Pump operation also causes higher pressure at the discharge side by forcing the fluid out at the outlet. There may be pressure sensing devices at the pump's suction and/or discharge sides which control the operation of the pump. For example, if the suction pressure of a centrifugal pump is too low, a device may trigger the pump to shut off to keep it from running dry; i. e. with no fluid entering.
Under normal conditions of atmospheric pressure suction can draw pure water up to a maximum height of approximately 10.3 m (33.9 feet or suction head). There is a theoretical limit of height that a perfect pump can raise water up a pipe and that is when the pump draws a perfect vacuum with no air in the suction pipe and atmospheric pressure of around 14 psi. In reality, no pumps are perfect. Leakage around the moving parts of the pump limit normal water pumps from starting if they lose prime. | https://www.wikidoc.org/index.php/Sucking | |
f4f894686067c1f089d9e861c7a4b17bd66e08ee | wikidoc | Sudafed | Sudafed
Sudafed is a brand name and registered trademark for a family of over-the-counter (OTC) decongestants manufactured by Pfizer Inc. for sale in the United States, the United Kingdom, Australia and Canada. The name is a reference to the active ingredient, pseudoephedrine hydrochloride, traditionally associated with the product; but, because of, legal restrictions on the sale of pseudoephedrine recently imposed in many markets, some products sold under the Sudafed brand name do not contain any form of pseudoephedrine.
# Switch to phenylephrine
In late 2004, Pfizer started publicly disclosing its plans to make available a new OTC product, Sudafed PE, which does not include pseudoephedrine. Sudafed PE contains a different decongestant called phenylephrine, in a formulation sold for years. Decongestants with other ingredients will be completely converted to phenylephrine later in 2005, though original Sudafed will still be offered.
The new product was prompted by existing and proposed restrictions on the availability of pseudoephedrine-based products. State laws imposing such restrictions were in response to pseudoephedrine's role as an ingredient used to produce the illegal and highly addictive stimulant methamphetamine, also known as crystal meth.
Pfizer and its predecessor Warner-Lambert had studied at least two alternatives to its current formula in anticipation of pressure from state regulators and the Food and Drug Administration:
- In 1996, the company began testing a patented decongestant ingredient known as "minus" pseudoephedrine. The company claimed animal tests showed this altered version offered sinus relief comparable to the current "plus" pseudoephedrine. The difference was that it couldn't be converted to methamphetamine, an illegal drug used recreationally. Pfizer did not bring the new ingredient to market because of the cost and time involved in gaining regulatory approval.
- Pfizer spent $12 million trying to develop additives for Sudafed that might make it harder to remove the pseudoephedrine it contains. They abandoned the project in 2003, seven years after announcing its existence.
According to L. Hendeles of the University of Florida, "Phenylpropanolamine, pseudoephedrine, and phenylephrine are the most common decongestants. Although all are sympathomimetic amines, their efficacy varies. In particular, phenylephrine is subject to first-pass metabolism and therefore is not bioavailable in currently recommended doses.", although 20mg doses do appear to be safe, and anecdotal evidence suggests greater decongestant action at this dose.
In Australia, Sudafed with up to 60mg of pseudoephedrine is available by prescription or subject to a pharmacist matching the purchaser's driver's license to a database and determining if the purchase history is consistent with personal use. If a driver's license is not provided, the pharmacist can, at his or her discretion, still provide the medication. | Sudafed
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Sudafed is a brand name and registered trademark for a family of over-the-counter (OTC) decongestants manufactured by Pfizer Inc. for sale in the United States, the United Kingdom, Australia and Canada. The name is a reference to the active ingredient, pseudoephedrine hydrochloride, traditionally associated with the product; but, because of, legal restrictions on the sale of pseudoephedrine recently imposed in many markets, some products sold under the Sudafed brand name do not contain any form of pseudoephedrine.
# Switch to phenylephrine
In late 2004, Pfizer started publicly disclosing its plans to make available a new OTC product, Sudafed PE, which does not include pseudoephedrine. Sudafed PE contains a different decongestant called phenylephrine, in a formulation sold for years. Decongestants with other ingredients will be completely converted to phenylephrine later in 2005, though original Sudafed will still be offered.
The new product was prompted by existing and proposed restrictions on the availability of pseudoephedrine-based products. State laws imposing such restrictions were in response to pseudoephedrine's role as an ingredient used to produce the illegal and highly addictive stimulant methamphetamine, also known as crystal meth.
Pfizer and its predecessor Warner-Lambert had studied at least two alternatives to its current formula in anticipation of pressure from state regulators and the Food and Drug Administration:
- In 1996, the company began testing a patented decongestant ingredient known as "minus" pseudoephedrine. The company claimed animal tests showed this altered version offered sinus relief comparable to the current "plus" pseudoephedrine. The difference was that it couldn't be converted to methamphetamine, an illegal drug used recreationally. Pfizer did not bring the new ingredient to market because of the cost and time involved in gaining regulatory approval.
- Pfizer spent $12 million trying to develop additives for Sudafed that might make it harder to remove the pseudoephedrine it contains. They abandoned the project in 2003, seven years after announcing its existence.
According to L. Hendeles of the University of Florida, "Phenylpropanolamine, pseudoephedrine, and phenylephrine are the most common decongestants. Although all are sympathomimetic amines, their efficacy varies. In particular, phenylephrine is subject to first-pass metabolism and therefore is not bioavailable in currently recommended doses."[1], although 20mg doses do appear to be safe, and anecdotal evidence suggests greater decongestant action at this dose.
In Australia, Sudafed with up to 60mg of pseudoephedrine is available by prescription or subject to a pharmacist matching the purchaser's driver's license to a database and determining if the purchase history is consistent with personal use. If a driver's license is not provided, the pharmacist can, at his or her discretion, still provide the medication. | https://www.wikidoc.org/index.php/Sudafed | |
27627f9c7081de580d19ce45550c1b5eaf969953 | wikidoc | Sulfone | Sulfone
A sulfone is a chemical compound containing a sulfonyl functional group attached to two carbon atoms. The central sulfur atom is twice double bonded to oxygen and has two further hydrocarbon substituents. The general structural formula is R-S(=O)(=O)-R' where R and R' are the organic groups. The use of the alternative name sulphone is discouraged by IUPAC. Sulfides are often the starting materials for sulfones by organic oxidation through the intermediate formation of sulfoxides. For example dimethyl sulfide is oxidized to dimethyl sulfoxide and then to dimethyl sulfone.
In the Ramberg-Bäcklund Reaction and the Julia olefination sulfones are converted to alkenes.
A sulfone can also be any of various organic sulfur compounds having a sulfonyl group attached to two carbon atoms, especially such a compound formerly used as an antibiotic to treat leprosy, dermatitis herpetiformis, tuberculosis, or Pneumocystis pneumonia(PCP). | Sulfone
A sulfone is a chemical compound containing a sulfonyl functional group attached to two carbon atoms. The central sulfur atom is twice double bonded to oxygen and has two further hydrocarbon substituents. The general structural formula is R-S(=O)(=O)-R' where R and R' are the organic groups. The use of the alternative name sulphone is discouraged by IUPAC. Sulfides are often the starting materials for sulfones by organic oxidation through the intermediate formation of sulfoxides. For example dimethyl sulfide is oxidized to dimethyl sulfoxide and then to dimethyl sulfone.
In the Ramberg-Bäcklund Reaction and the Julia olefination sulfones are converted to alkenes.
A sulfone can also be any of various organic sulfur compounds having a sulfonyl group attached to two carbon atoms, especially such a compound formerly used as an antibiotic to treat leprosy, dermatitis herpetiformis, tuberculosis, or Pneumocystis pneumonia(PCP). | https://www.wikidoc.org/index.php/Sulfone | |
58228a46c1d3d1c3f61e2524ff1aef13be3a339c | wikidoc | Sunburn | Sunburn
# Overview
A sunburn is a burn to living tissue such as skin produced by overexposure to ultraviolet (UV) radiation, commonly from the sun's rays. Exposure of the skin to lesser amounts of UV will often produce a suntan. Usual mild symptoms in humans and animals are red or reddish skin that is hot to the touch, general fatigue, and mild dizziness. Sunburn can be life-threatening and is a leading cause of skin cancer. Sunburn can easily be prevented through the use of sunscreen, clothing (and hats), and by limiting solar exposure, especially during the middle of the day. The only cure for sunburn is slow healing, although skin creams can help.
# Cause
The condition occurs when incident UV radiation exceeds the existing protective capacity of melanin in the skin. Concentrations of this pigment vary greatly among individuals, but in general, darker-skinned people have more melanin than those with lighter skin. Correspondingly, the incidence of sunburn among dark-skinned individuals is lower.
The sun is not the only origin — a similar burn can be produced by overexposure to other sources of UV such as from tanning lamps, or occupationally, such as from welding arcs.
# Symptoms
Typically there is initial redness (erythema), followed by varying degrees of pain, both proportional in severity to the duration and intensity of exposure.
Other symptoms are edema, itching, red and/or peeling skin, rash, nausea and fever. Also, a small amount of heat is given off from the burn, giving a warm feeling to the affected area. Sunburns may be first- or second-degree burns.
## Variations
Minor sunburns typically cause nothing more than slight redness and tenderness to the affected areas. In more serious cases blistering can occur. Extreme sunburns can be painful to the point of debilitation and may require hospital care.
## Duration
Sunburn can occur in less than 15 minutes. Nevertheless, the inflicted harm is often not immediately obvious.
After the exposure, skin may turn red in as little as 30 minutes but most often takes 2 to 6 hours. Pain is usually most extreme 6 to 48 hours after exposure. The burn continues to develop for 24 to 72 hours occasionally followed by peeling skin in 3 to 8 days. Some peeling and itching may continue for several weeks.
# UVA and UVB
UV radiation is divided into the UVA (380–315 nm), UVB (315–280 nm) and UVC (280-180 nm) sub-bands. Ozone in the Earth's atmosphere filters out a portion of this before it reaches the planet's surface. UVC is almost entirely eliminated by the atmosphere, but enough UVA and UVB penetrates it in large enough quantities that sunburn occurs.
With respect to the spectral components of sunlight, the severity of sunburn has been found to peak in the low-frequency UVB range near the 320 nm transition to UVA. This is based on two factors:
- Erythemal activity - the specific effect of different wavelengths of radiation on the skin
- solar irradiance - how much of any solar radiation wavelength can be expected to be incident on the surface of the earth
The resulting erythemal irradiance metric is calculated by weighting measurements of solar irradiance with experimental measurements of erythemal activity. When this product is graphed, there is a peak at 308 nm.
At the cellular level, UVB light causes DNA damage which may be passed onto subsequent generations of a cell's progeny, leading to increased risk of skin cancer. Damaged cells die and release toxins which are responsible for nausea and fever. If many cells die, peeling may result.
# Increased risk
The risk of sunburn increases with proximity to the tropic latitudes which are located between 23.5° north and south latitude. Everything else being equal (e.g. cloud cover, ozone layer, terrain, etc.), over the course of a full year, each location within the tropic and polar regions receives the same amount of UV radiation. It is in the temperate zones between 23.5° and 66.5° where UV radiation varies by latitude. The lower the latitude, the greater the risk. In the late spring and early summer, higher latitudes have many hours of daylight, which partially compensates for the less direct sunlight in this region if exposed all day. People can still receive severe sunburns at these higher latitudes.
On a minute by minute basis though, the amount of UV radiation is dependent on the angle of the sun. This is easily determined by the height ratio of any object to the size of its shadow. The greatest risk is at noon, when shadows are at their minimum. Regardless of one's latitude (assuming no other variables), equal shadow lengths mean equal amounts of UV radiation.
Sunburn can also be caused by pharmaceutical products that sensitise some users to UV radiation. Certain antibiotics, contraceptives, and tranquillizers have this effect. People with red hair and/or freckles generally have a greater risk of sunburn than others because of their lighter skin tone.
Suntans, which naturally develop in some individuals as a protective mechanism against the sun, are viewed by many in the Western world as desirable. This has led to increases in sunburn incidences and in solarium popularity as individuals attempt to tan.
In recent years, the incidence and severity of sunburn has increased worldwide, especially in the southern hemisphere, because of damage to the ozone layer. Ozone depletion and the seasonal ozone hole has led to dangerously high levels of UV radiation . Incidence of skin cancer in Queensland, Australia has risen to 75 percent among those over 64 years of age by about 1990, presumably due to thinning of the ozone layer.
No one is immune from sun-induced skin cancer, but there are several factors that dramatically increase the risk. Fair-skinned individuals are the most prone to sun damage, as are people taking medications that contraindicate sun exposure.
One should immediately speak to a dermatologist if a skin lesion appears suddenly, with asymmetrical appearance, darker edges than center, that changes color, or becomes larger than 1/4 inch (6 mm).
# Protection
## Skin
It is advisable to consult a UV index to determine what level of protection is necessary. Potential forms of protection include wearing long-sleeved garments and wide-brimmed hats, and using an umbrella when in the sun. Minimization of sun exposure between the hours of 10 a.m. to 3 p.m. is also recommended.
Commercial preparations are available that block UV light, known as sunscreens or sunblocks. They have a Sun Protection Factor (SPF) rating, based on the sunblock's ability to reduce the UVB radiation at the skin: The higher the SPF rating, the greater the protection. A sunscreen rated SPF15 blocks 93.3% UVB; an SPF30 rated sunscreen blocks 96.7%. It is best to use a broad spectrum sunscreen to protect against both UVA and UVB radiation. It is prudent to use waterproof formulations if one plans to engage in water-based activities. The best sunscreens attenuate UVA radiation as well as UVB. Note that the stated protection factors are only correct if 2μl of sunscreen is applied per square cm of exposed skin. This translates into about 28 ml (1 oz) to cover the whole body of an adult male, which is much more than many people use in practice.
Contrary to the common advice that sunscreen should be reapplied every 2–3 hours, research has shown that the best protection is achieved by application 15 to 30 minutes before exposure, followed by one reapplication 15 to 30 minutes after the sun exposure begins. Further reapplication is only necessary after activities such as swimming, sweating, and rubbing. This varies based on the indications and protection shown on the label — from as little as 80 minutes in water to a few hours, depending on the product selected.
When one is exposed to any artificial source of occupational UV, special protective clothing (for example, welding helmets/shields) should be worn.
## Eyes
Eyes should not be neglected, and wrap-around sunglasses which block UV light should also be worn. UV light has been implicated in pterygium and cataract development.
# Treatment
There is no immediate cure for sunburns, but the pain can be relieved by hydrating the skin. This is done by applying products containing aloe, vitamin E, or both. Vinegar is a remedy for the stinging sensation on a burn and any products with lidocaine can prevent healing and damage skin. Drinking fluids can aid in hydration, and eating high protein foods will assist tissue repair. Analgesics such as acetaminophen (e.g. Tylenol) or ibuprofen (e.g. Advil) can also reduce pain. One method to treatment involves applying a clean washcloth soaked with cool milk like a cold compress, since the lactic acid will help reduce inflammation and the cool towel will soothe the pain.
Blistered skin, with or without open sores, should heal on its own. As with any other open skin wound, it is best to avoid lotions or other directly applied ointments. However, antibacterial solutions and gauze can prevent skin infections.
The best treatment for most sunburns is time. Given a few weeks, they will heal. Overall, the most important aspect of sunburn care is to avoid the sun while healing, and to take precautions to prevent future burns.
# Skin cancer
The more critical and long-term danger posed by sunburn is an increased risk of future skin cancer, which is believed to be highly correlated. One incident of blistering sunburn doubles the risk of malignant melanoma . But while sunburn severity gives an indication of short-term radiation over-exposure, there is also deeper penetration by UVA that occurs in the absence of perceptible symptoms. UVB was thought to be the sole causative agent in skin cancer, but there is a growing body of evidence to support the theory that both UVA and UVB are implicated.
# Non-human sunburn
Many non-human animals can suffer from sunburn; however, many are protected by a layer of dense fur. Despite myths stating that only hippopotamuses and pigs can be affected by sunburn, almost all animals—even fish, given the right conditions—can suffer sunburn (though pigs and hippopotamuses are more prone due to their hairless skin producing less oil, a natural sun protector). The Tamworth Pig has adapted a special bristle density to minimize sunburn.
Variations in pigment, fur density, and genetic mutations such as albinism can make some individuals within the same species more or less prone to sunburn. Special care must be taken to protect individuals with variations that are more prone.
Sunburn is not limited to humans and other animals. Sunburn is a significant and common cause of damage to trees and plants. Plant related sunburn also involves damage to tissue, caused by light from the sun. "Sunscald" on trees is not the same as sunburn on trees. Sunscald is typically a winter or cool season injury to trees. Trunk and branch tissue can be damaged from exposure to sunlight. Damage typically occurs on the west side, to bark (tissue beneath) facing afternoon warm-season sunlight. Bark can fall off, leaving exposed dry wood - clearly seen here where a cavity developed after undamaged tissue continued to grow on either side of the sunburned area. Prevention includes protective trunk cover for newly planted trees, and avoiding excess foliage removal while pruning.
Some nectar producing foliage can suffer sun scorching as the nectar magnifies the sun's rays and can burn through the leaf in certain circumstances.
# Related Chapters
- Hyperthermia (heat stroke)
- Windburn | Sunburn
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
A sunburn is a burn to living tissue such as skin produced by overexposure to ultraviolet (UV) radiation, commonly from the sun's rays. Exposure of the skin to lesser amounts of UV will often produce a suntan. Usual mild symptoms in humans and animals are red or reddish skin that is hot to the touch, general fatigue, and mild dizziness. Sunburn can be life-threatening and is a leading cause of skin cancer.[1][2] Sunburn can easily be prevented through the use of sunscreen, clothing (and hats), and by limiting solar exposure, especially during the middle of the day. The only cure for sunburn is slow healing, although skin creams can help.
# Cause
The condition occurs when incident UV radiation exceeds the existing protective capacity of melanin in the skin. Concentrations of this pigment vary greatly among individuals, but in general, darker-skinned people have more melanin than those with lighter skin. Correspondingly, the incidence of sunburn among dark-skinned individuals is lower.
The sun is not the only origin — a similar burn can be produced by overexposure to other sources of UV such as from tanning lamps, or occupationally, such as from welding arcs.
# Symptoms
Typically there is initial redness (erythema), followed by varying degrees of pain, both proportional in severity to the duration and intensity of exposure.
Other symptoms are edema, itching, red and/or peeling skin, rash, nausea and fever. Also, a small amount of heat is given off from the burn, giving a warm feeling to the affected area. Sunburns may be first- or second-degree burns.
## Variations
Minor sunburns typically cause nothing more than slight redness and tenderness to the affected areas. In more serious cases blistering can occur. Extreme sunburns can be painful to the point of debilitation and may require hospital care.
## Duration
Sunburn can occur in less than 15 minutes. Nevertheless, the inflicted harm is often not immediately obvious.
After the exposure, skin may turn red in as little as 30 minutes but most often takes 2 to 6 hours. Pain is usually most extreme 6 to 48 hours after exposure. The burn continues to develop for 24 to 72 hours occasionally followed by peeling skin in 3 to 8 days. Some peeling and itching may continue for several weeks.
# UVA and UVB
UV radiation is divided into the UVA (380–315 nm), UVB (315–280 nm) and UVC (280-180 nm) sub-bands. Ozone in the Earth's atmosphere filters out a portion of this before it reaches the planet's surface. UVC is almost entirely eliminated by the atmosphere, but enough UVA and UVB penetrates it in large enough quantities that sunburn occurs.[3]
With respect to the spectral components of sunlight, the severity of sunburn has been found to peak in the low-frequency UVB range near the 320 nm transition to UVA. This is based on two factors:
- Erythemal activity - the specific effect of different wavelengths of radiation on the skin
- solar irradiance - how much of any solar radiation wavelength can be expected to be incident on the surface of the earth
The resulting erythemal irradiance metric is calculated by weighting measurements of solar irradiance with experimental measurements of erythemal activity. When this product is graphed, there is a peak at 308 nm.
At the cellular level, UVB light causes DNA damage which may be passed onto subsequent generations of a cell's progeny, leading to increased risk of skin cancer. Damaged cells die and release toxins which are responsible for nausea and fever. If many cells die, peeling may result.
# Increased risk
The risk of sunburn increases with proximity to the tropic latitudes which are located between 23.5° north and south latitude. Everything else being equal (e.g. cloud cover, ozone layer, terrain, etc.), over the course of a full year, each location within the tropic and polar regions receives the same amount of UV radiation. It is in the temperate zones between 23.5° and 66.5° where UV radiation varies by latitude. The lower the latitude, the greater the risk. In the late spring and early summer, higher latitudes have many hours of daylight, which partially compensates for the less direct sunlight in this region if exposed all day. People can still receive severe sunburns at these higher latitudes.
On a minute by minute basis though, the amount of UV radiation is dependent on the angle of the sun. This is easily determined by the height ratio of any object to the size of its shadow. The greatest risk is at noon, when shadows are at their minimum. Regardless of one's latitude (assuming no other variables), equal shadow lengths mean equal amounts of UV radiation.
Sunburn can also be caused by pharmaceutical products that sensitise some users to UV radiation. Certain antibiotics, contraceptives, and tranquillizers have this effect.[4] People with red hair and/or freckles generally have a greater risk of sunburn than others because of their lighter skin tone.[5]
Suntans, which naturally develop in some individuals as a protective mechanism against the sun, are viewed by many in the Western world as desirable.[6] This has led to increases in sunburn incidences and in solarium popularity as individuals attempt to tan.
In recent years, the incidence and severity of sunburn has increased worldwide, especially in the southern hemisphere, because of damage to the ozone layer. Ozone depletion and the seasonal ozone hole has led to dangerously high levels of UV radiation [7]. Incidence of skin cancer in Queensland, Australia has risen to 75 percent among those over 64 years of age by about 1990, presumably due to thinning of the ozone layer.[8]
No one is immune from sun-induced skin cancer, but there are several factors that dramatically increase the risk. Fair-skinned individuals are the most prone to sun damage, as are people taking medications that contraindicate sun exposure.
One should immediately speak to a dermatologist if a skin lesion appears suddenly, with asymmetrical appearance, darker edges than center, that changes color, or becomes larger than 1/4 inch (6 mm).
# Protection
## Skin
It is advisable to consult a UV index to determine what level of protection is necessary. Potential forms of protection include wearing long-sleeved garments and wide-brimmed hats, and using an umbrella when in the sun. Minimization of sun exposure between the hours of 10 a.m. to 3 p.m. is also recommended.
Commercial preparations are available that block UV light, known as sunscreens or sunblocks. They have a Sun Protection Factor (SPF) rating, based on the sunblock's ability to reduce the UVB radiation at the skin: The higher the SPF rating, the greater the protection. A sunscreen rated SPF15 blocks 93.3% UVB; an SPF30 rated sunscreen blocks 96.7%. It is best to use a broad spectrum sunscreen to protect against both UVA and UVB radiation.[9] It is prudent to use waterproof formulations if one plans to engage in water-based activities. The best sunscreens attenuate UVA radiation as well as UVB. Note that the stated protection factors are only correct if 2μl of sunscreen is applied per square cm of exposed skin. This translates into about 28 ml (1 oz) to cover the whole body of an adult male, which is much more than many people use in practice.
Contrary to the common advice that sunscreen should be reapplied every 2–3 hours, research has shown that the best protection is achieved by application 15 to 30 minutes before exposure, followed by one reapplication 15 to 30 minutes after the sun exposure begins. Further reapplication is only necessary after activities such as swimming, sweating, and rubbing.[10] This varies based on the indications and protection shown on the label — from as little as 80 minutes in water to a few hours, depending on the product selected.
When one is exposed to any artificial source of occupational UV, special protective clothing (for example, welding helmets/shields) should be worn.
## Eyes
Eyes should not be neglected, and wrap-around sunglasses which block UV light should also be worn. UV light has been implicated in pterygium and cataract development.
# Treatment
There is no immediate cure for sunburns, but the pain can be relieved by hydrating the skin. This is done by applying products containing aloe, vitamin E, or both.[11] Vinegar is a remedy for the stinging sensation on a burn and any products with lidocaine can prevent healing and damage skin. Drinking fluids can aid in hydration, and eating high protein foods will assist tissue repair. Analgesics such as acetaminophen (e.g. Tylenol) or ibuprofen (e.g. Advil) can also reduce pain.[11] One method to treatment involves applying a clean washcloth soaked with cool milk like a cold compress, since the lactic acid will help reduce inflammation and the cool towel will soothe the pain.[12]
Blistered skin, with or without open sores, should heal on its own. As with any other open skin wound, it is best to avoid lotions or other directly applied ointments. However, antibacterial solutions and gauze can prevent skin infections.
The best treatment for most sunburns is time. Given a few weeks, they will heal.[11] Overall, the most important aspect of sunburn care is to avoid the sun while healing, and to take precautions to prevent future burns.
# Skin cancer
The more critical and long-term danger posed by sunburn is an increased risk of future skin cancer, which is believed to be highly correlated. One incident of blistering sunburn doubles the risk of malignant melanoma[13] [2]. But while sunburn severity gives an indication of short-term radiation over-exposure, there is also deeper penetration by UVA that occurs in the absence of perceptible symptoms. UVB was thought to be the sole causative agent in skin cancer, but there is a growing body of evidence to support the theory that both UVA and UVB are implicated.[14]
# Non-human sunburn
Many non-human animals can suffer from sunburn; however, many are protected by a layer of dense fur. Despite myths stating that only hippopotamuses and pigs can be affected by sunburn, almost all animals—even fish, given the right conditions—can suffer sunburn (though pigs and hippopotamuses are more prone due to their hairless skin producing less oil, a natural sun protector). The Tamworth Pig has adapted a special bristle density to minimize sunburn.
Variations in pigment, fur density, and genetic mutations such as albinism can make some individuals within the same species more or less prone to sunburn. Special care must be taken to protect individuals with variations that are more prone.[15]
Sunburn is not limited to humans and other animals. Sunburn is a significant and common cause of damage to trees and plants. Plant related sunburn also involves damage to tissue, caused by light from the sun. "Sunscald" on trees is not the same as sunburn on trees. Sunscald is typically a winter or cool season injury to trees. Trunk and branch tissue can be damaged from exposure to sunlight. Damage typically occurs on the west side, to bark (tissue beneath) facing afternoon warm-season sunlight. Bark can fall off, leaving exposed dry wood - clearly seen here where a cavity developed after undamaged tissue continued to grow on either side of the sunburned area. Prevention includes protective trunk cover for newly planted trees, and avoiding excess foliage removal while pruning.
Some nectar producing foliage can suffer sun scorching as the nectar magnifies the sun's rays and can burn through the leaf in certain circumstances.
# Related Chapters
- Hyperthermia (heat stroke)
- Windburn | https://www.wikidoc.org/index.php/Sun_exposure | |
5e5153eb8c7014ab40ba27755b9d77ed652ade7d | wikidoc | Suramin | Suramin
# Overview
Suramin is an antimicrobial drug developed by Oskar Dressel and Richard Kothe of Bayer, Germany in 1916, and is still sold by Bayer under the brand name Germanin. The formula of suramin was kept secret by Bayer for commercial reasons, however, it was elucidated and published in 1924 by Ernest Fourneau and his team of the Pasteur Institute.
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.
# Medical uses
## Protozoa
It is used for treatment of human sleeping sickness caused by trypanosomes.
## Helminthiasis
It has been used in the treatment of onchocerciasis.
## Other
It has been investigated as treatment for prostate cancer.
Also, suramin as treatment for autism is being evaluated and there are promising results in adult mice.
# Adverse reactions
The most frequent adverse reactions are nausea and vomiting.
About 90% of patients will get an urticarial rash that disappears in a few days without needing to stop treatment. There is a greater than 50% chance of adrenal cortical damage, but only a smaller proportion will require lifelong corticosteroid replacement. It is common for patients to get a tingling or crawling sensation of the skin with suramin. Suramin will cause clouding of the urine which is harmless: patients should be warned of this to avoid them becoming alarmed.
Kidney damage and exfoliative dermatitis occur less commonly.
Suramin has been applied clinically to HIV/AIDS patients resulting in a significant number of fatal occurrences and as a result the application of this molecule was abandoned for this condition.
# Chemistry
The molecular formula of suramin is C51H40N6O23S6. It is a symmetric molecule in the center of which lies a urea (NH–CO–NH) functional group. Suramin contains eight benzene rings, four of which are fused in pairs (naphthalene), four amide groups (in addition to the urea) and six sulfonic acid groups. When given as drug, it is usually as the sodium sulfonate, with six sodium ions on the sulfonate groups rather than hydrogens.
# Research
According to the National Cancer Institute there are no active clinical trials.
Suramin is also used in research as a broad-spectrum antagonist of P2 receptors and agonist of Ryanodine receptors.
Its effect on telomerase has been investigated.
It may have some activity against RNA viruses.
In addition to antagonism of P2 receptors, Suramin inhibits the activation of heterotrimeric G proteins in a variety of other GPCRs with varying potency. It prevents the association of heteromeric G proteins and therefore the receptors guanine exchange functionality (GEF). With this blockade the GDP will not release from the Gα subunit so it can not be replaced by a GTP and become activated. This has the effect of blocking downstream G protein mediated signaling of various GPCR proteins including rhodopsin, the A1 adenosine receptor, and the D2 dopamine receptor. | Suramin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]
# Overview
Suramin is an antimicrobial drug developed by Oskar Dressel and Richard Kothe of Bayer, Germany in 1916, and is still sold by Bayer under the brand name Germanin. The formula of suramin was kept secret by Bayer for commercial reasons, however, it was elucidated and published in 1924 by Ernest Fourneau and his team of the Pasteur Institute.[1]
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[2]
# Medical uses
## Protozoa
It is used for treatment of human sleeping sickness caused by trypanosomes.[3]
## Helminthiasis
It has been used in the treatment of onchocerciasis.[4]
## Other
It has been investigated as treatment for prostate cancer.[5]
Also, suramin as treatment for autism is being evaluated[6] and there are promising results in adult mice.[7][8]
# Adverse reactions
The most frequent adverse reactions are nausea and vomiting.
About 90% of patients will get an urticarial rash that disappears in a few days without needing to stop treatment. There is a greater than 50% chance of adrenal cortical damage, but only a smaller proportion will require lifelong corticosteroid replacement. It is common for patients to get a tingling or crawling sensation of the skin with suramin. Suramin will cause clouding of the urine which is harmless: patients should be warned of this to avoid them becoming alarmed.
Kidney damage and exfoliative dermatitis occur less commonly.
Suramin has been applied clinically to HIV/AIDS patients resulting in a significant number of fatal occurrences and as a result the application of this molecule was abandoned for this condition.[9]
# Chemistry
The molecular formula of suramin is C51H40N6O23S6. It is a symmetric molecule in the center of which lies a urea (NH–CO–NH) functional group. Suramin contains eight benzene rings, four of which are fused in pairs (naphthalene), four amide groups (in addition to the urea) and six sulfonic acid groups. When given as drug, it is usually as the sodium sulfonate, with six sodium ions on the sulfonate groups rather than hydrogens.
# Research
According to the National Cancer Institute there are no active clinical trials.[10]
Suramin is also used in research as a broad-spectrum antagonist of P2 receptors[11][12] and agonist of Ryanodine receptors.[13]
Its effect on telomerase has been investigated.[14]
It may have some activity against RNA viruses.[15]
In addition to antagonism of P2 receptors, Suramin inhibits the activation of heterotrimeric G proteins in a variety of other GPCRs with varying potency. It prevents the association of heteromeric G proteins and therefore the receptors guanine exchange functionality (GEF). With this blockade the GDP will not release from the Gα subunit so it can not be replaced by a GTP and become activated. This has the effect of blocking downstream G protein mediated signaling of various GPCR proteins including rhodopsin, the A1 adenosine receptor, and the D2 dopamine receptor.[16] | https://www.wikidoc.org/index.php/Suramin | |
7fe259b7d1114ad9ee47729ef20ae321f21a0fb2 | wikidoc | Sylvite | Sylvite
Sylvite is potassium chloride (KCl) in natural mineral form. It forms crystals in the isometric system very similar to normal rock salt, halite (NaCl). (The two are, in fact, isomorphous. Sylvite is colorless to white with shades of yellow and red due to inclusions. It has a Mohs hardness of 2.5 and a specific gravity of 1.99. It has a refractive index of n=1.490) . Sylvite has a salty taste with a distinct bitterness.
Sylvite is one of the last evaporite minerals to precipitate out of solution. As such, it is only found in very dry saline areas. Its principal use is as a potassium fertilizer.
Sylvite is found in many evaporite deposits worldwide. Massive bedded deposits occur in New Mexico and western Texas, and in Utah in the US, but the largest world source is in Saskatchewan, Canada. The vast deposits in Saskatchewan, Canada were formed by the evaporation of a Devonian seaway. Sylvite is the official mineral of Saskatchewan.
Sylvite was first described in 1832 at Mt. Vesuvius near Napoli in Italy and named for the Dutch chemist, François Sylvius de le Boe (1614-1672). | Sylvite
Template:Infobox mineral
Sylvite is potassium chloride (KCl) in natural mineral form. It forms crystals in the isometric system very similar to normal rock salt, halite (NaCl). (The two are, in fact, isomorphous. [1] Sylvite is colorless to white with shades of yellow and red due to inclusions. It has a Mohs hardness of 2.5 and a specific gravity of 1.99. It has a refractive index of n=1.490) [2]. Sylvite has a salty taste with a distinct bitterness.
Sylvite is one of the last evaporite minerals to precipitate out of solution. As such, it is only found in very dry saline areas. Its principal use is as a potassium fertilizer.
Sylvite is found in many evaporite deposits worldwide. Massive bedded deposits occur in New Mexico and western Texas, and in Utah in the US, but the largest world source is in Saskatchewan, Canada. The vast deposits in Saskatchewan, Canada were formed by the evaporation of a Devonian seaway. Sylvite is the official mineral of Saskatchewan.
Sylvite was first described in 1832 at Mt. Vesuvius near Napoli in Italy and named for the Dutch chemist, François Sylvius de le Boe (1614-1672). | https://www.wikidoc.org/index.php/Sylvite | |
ad5dd76aa380d74f704e34d3fb93a009b8575a37 | wikidoc | Synanon | Synanon
Synanon was initially a drug rehabilitation program founded by Charles "Chuck" Dederich Sr. (1913–1997) in 1958 in Santa Monica, California. By the early 1960s it had become an alternative community as well, attracting people with its emphasis on living a self-examined life, as aided by group truth-telling sessions known as the "Synanon Game." Synanon ultimately became the cultish Church of Synanon in the 1970s and the group disbanded permanently in 1989 due to difficulties with the Internal Revenue Service.
# Beginnings
Dederich was a reformed alcoholic and member of Alcoholics Anonymous. He made a positive impression as a speaker at A.A. meetings. Drug addicts, because they were considered significantly different from alcoholics, were not accepted into A.A. at that time, so Dederich created his own program to address their needs. He is said to have coined the phrase "today is the first day of the rest of your life" In 1965 Columbia Pictures produced Synanon, directed by Richard Quine, starring Edmond O'Brien as Chuck Dederich, with Chuck Connors, Stella Stevens, Richard Conte, and Eartha Kitt. (See Template:Imdb title.)
Synanon began as a two-year residential program, but Dederich soon concluded that, because full recovery was never possible, members could never graduate. The organization developed a business that sold promotional items, a successful enterprise that generated roughly $10 million per year of revenue.
Synanon purchased the Club Casa del Mar, a large beachside 1926 hotel in Santa Monica, and used it as a headquarters and dormitory for drug treatment. Subsequently, Synanon acquired a large industrial building in Oakland, California, transforming it into a residential facility for its members; outsiders were permitted to attend the "Game" there as well. Children were reared communally in the Synanon School and juveniles were often sent to Synanon by the courts. Professionals, even those without drug addictions, were eagerly invited, provided they transferred their assets to the organization. Control over members occurred through the "Synanon Game." The "Game" could be considered a therapeutic tool, likened to group therapy; or a social control, in which members humiliated one another and encouraged the exposure of one's innermost weaknesses, or both. Beginning in the mid-1970s, women were required to shave their heads, married couples were made to break up and take new partners, males were given forced vasectomies, and a few pregnant women were even required to have abortions. George Lucas needed many people with shaved heads in order to film THX 1138, so he hired some of his extras from Synanon. Robert Altman hired members of Synanon as extras for gambling scenes in his 1974 film California Split.
# Lifetime rehabilitation concept
Beginning in 1974 the authorities began to question Synanon's promises and practices. The concept of "lifetime rehabilitation" did not agree with therapeutic norms, and it was alleged that the group was running an unauthorized medical clinic, and that on remote properties in California such as Tomales Bay in Marin County and Badger, Tulare County, the organization had built unpermitted buildings, a trash dump and an airstrip. Tax issues arose. In response to these accusations, Dederich declared that Synanon was a tax exempt religious organization, the "Church of Synanon."
The problems remained despite the changes. Children assigned to Synanon began running away, helped by an "underground railroad" that sought to return them to their parents. Beatings of opponents and ex-members, "splittees," occurred across the state. A Grand Jury in Los Angeles issued a scathing report in 1978 attacking Synanon for its child abuse and for the profits that flowed to Dederich, and also attacking authorities for their lack of oversight. Remarkably, the authorities refused to intercede. Though local newspapers and broadcast media covered the case, they were largely silenced by lawsuits from Synanon lawyers charging libel. Those suits ultimately turned out to be Synanon's undoing, giving journalists access to internal documents.
# Criminal behavior
On March 20, 1978, a former member of Synanon was severely beaten (for being a "splittee") during his honeymoon when he took his bride to show her where he had once lived on the Walker Creek Ranch.
They also beat a neighbouring rancher who was helping children run away from Synanon and return to their parents.
In the summer of 1978 NBC produced a "hard hitting" news segment on Synanon. Following its broadcast, executives of the network and its corporate chairman received hundreds of threats from Synanon members and supporters, including letters that said, "Your actions place you in legal and physical peril" and "We are going to teach you a lesson you will never forget."
On September 21 1978 ex-member Phil Ritter, was beaten into a coma by two members, which lasted for one week. Fluid leaked into his spine causing a near fatal case of spinal meningitis.
Several weeks later, October 11 1978, two Synanon members placed a de-rattled rattlesnake in the mailbox of attorney Paul Morantz in Pacific Palisades, California. Morantz had successfully brought suit on behalf of a woman abducted by Synanon. The snake bit Morantz but did not kill him.
Six weeks later the Los Angeles Police Department performed a search of the ranch in Badger that turned up a recorded speech by Dederich in which he said, ""We're not going to mess with the old-time, turn-the-other-cheek religious postures ... our religious posture is: Don't mess with us. You can get killed dead, literally dead...these are real threats," he snarls. "They are draining life's blood from us and expecting us to play by their silly rules. We will make the rules. I see nothing frightening about it ... I am quite willing to break some lawyer's legs and next break his wife's legs and threaten to cut their child's arm off. That is the end of that lawyer. That is a very satisfactory, humane way of transmitting information. ... I really do want an ear in a glass of alcohol on my desk."
A drunken Dederich was arrested on December 2. The two other Synanon residents, one of whom was Lance Kenton, son of musician Stan Kenton, pleaded "no contest" to charges of assault and conspiracy to commit murder. While his associates went to jail, Dederich avoided imprisonment by formally stepping down as Chairman of Synanon.
Much of the violence was carried out by a group within Synanon called the "Imperial Marines."
The tiny Point Reyes Light, a weekly newspaper in Marin County, received the Pulitzer Prize for Public Service in 1979 on account of its coverage of Synanon when other news outlets avoided covering the group.
Synanon struggled to survive without its leader and with a severely tarnished reputation. The Internal Revenue Service revoked the group's tax exemption and the properties were confiscated or sold. By the mid-1990s the community had essentially folded.
# Successes
Despite its faults, the Synanon program worked for many individuals. Among other successes, it is credited with curing heroin-addicted jazz musicians Frank Rehak, Joe Pass and Art Pepper (Pepper discusses his Synanon experiences at length in his autobiography Straight Life), and actor Matthew "Stymie" Beard. In 1962 Pass formed a band made up of Synanon patients who recorded an album titled, The Sounds of Synanon. The organization was touted by motivational speaker Florrie Fisher in her speeches to high schoolers, and she credited it with curing her of a heroin addiction. It also inspired more moderate, successful programs such as Delancey Street, co-founded by John Maher, a former Synanon member. Many former members still value the positive aspects of Synanon, primarily its strong sense of community, and remain in close contact, personally or through online chat groups, and some even own businesses together.
A branch of Synanon founded in Germany in 1971 is still in operation.
# Popular depictions
Synanon is referenced in the Bob Dylan song "Lenny Bruce," from his 1981 album Shot of Love. Producer/writer J. Michael Straczynski used a version of the Synanon Game in his Science Fiction series Babylon 5 (episode "Signs and Portents"). The New-Path drug treatment centers in Phillip K. Dick's novel A Scanner Darkly bear numerous similarities to Synanon. | Synanon
Template:Infobox Company
Synanon was initially a drug rehabilitation program founded by Charles "Chuck" Dederich Sr. (1913–1997) in 1958 in Santa Monica, California. By the early 1960s it had become an alternative community as well, attracting people with its emphasis on living a self-examined life, as aided by group truth-telling sessions known as the "Synanon Game." Synanon ultimately became the cultish Church of Synanon in the 1970s and the group disbanded permanently in 1989 due to difficulties with the Internal Revenue Service.
# Beginnings
Dederich was a reformed alcoholic and member of Alcoholics Anonymous. He made a positive impression as a speaker at A.A. meetings. Drug addicts, because they were considered significantly different from alcoholics, were not accepted into A.A. at that time, so Dederich created his own program to address their needs. He is said to have coined the phrase "today is the first day of the rest of your life"[1][2] In 1965 Columbia Pictures produced Synanon, directed by Richard Quine, starring Edmond O'Brien as Chuck Dederich, with Chuck Connors, Stella Stevens, Richard Conte, and Eartha Kitt. (See Template:Imdb title.)
Synanon began as a two-year residential program, but Dederich soon concluded that, because full recovery was never possible, members could never graduate. The organization developed a business that sold promotional items, a successful enterprise that generated roughly $10 million per year of revenue.
Synanon purchased the Club Casa del Mar, a large beachside 1926 hotel in Santa Monica, and used it as a headquarters and dormitory for drug treatment. Subsequently, Synanon acquired a large industrial building in Oakland, California, transforming it into a residential facility for its members; outsiders were permitted to attend the "Game" there as well. Children were reared communally in the Synanon School and juveniles were often sent to Synanon by the courts. Professionals, even those without drug addictions, were eagerly invited, provided they transferred their assets to the organization. Control over members occurred through the "Synanon Game." The "Game" could be considered a therapeutic tool, likened to group therapy; or a social control, in which members humiliated one another and encouraged the exposure of one's innermost weaknesses, or both.[3] Beginning in the mid-1970s, women were required to shave their heads, married couples were made to break up and take new partners, males were given forced vasectomies, and a few pregnant women were even required to have abortions.[4][5] George Lucas needed many people with shaved heads in order to film THX 1138, so he hired some of his extras from Synanon. Robert Altman hired members of Synanon as extras for gambling scenes in his 1974 film California Split.
# Lifetime rehabilitation concept
Beginning in 1974 the authorities began to question Synanon's promises and practices. The concept of "lifetime rehabilitation" did not agree with therapeutic norms, and it was alleged that the group was running an unauthorized medical clinic, and that on remote properties in California such as Tomales Bay in Marin County and Badger, Tulare County, the organization had built unpermitted buildings, a trash dump and an airstrip. Tax issues arose. In response to these accusations, Dederich declared that Synanon was a tax exempt religious organization, the "Church of Synanon."
The problems remained despite the changes. Children assigned to Synanon began running away, helped by an "underground railroad" that sought to return them to their parents. Beatings of opponents and ex-members, "splittees," occurred across the state. A Grand Jury in Los Angeles issued a scathing report in 1978 attacking Synanon for its child abuse and for the profits that flowed to Dederich, and also attacking authorities for their lack of oversight. Remarkably, the authorities refused to intercede. Though local newspapers and broadcast media covered the case, they were largely silenced by lawsuits from Synanon lawyers charging libel. Those suits ultimately turned out to be Synanon's undoing, giving journalists access to internal documents.
# Criminal behavior
On March 20, 1978, a former member of Synanon was severely beaten (for being a "splittee") during his honeymoon when he took his bride to show her where he had once lived on the Walker Creek Ranch.
They also beat a neighbouring rancher who was helping children run away from Synanon and return to their parents.
In the summer of 1978 NBC produced a "hard hitting" news segment on Synanon. Following its broadcast, executives of the network and its corporate chairman received hundreds of threats from Synanon members and supporters, including letters that said, "Your actions place you in legal and physical peril" and "We are going to teach you a lesson you will never forget."[6]
On September 21 1978 ex-member Phil Ritter, was beaten into a coma by two members, which lasted for one week. Fluid leaked into his spine causing a near fatal case of spinal meningitis.
Several weeks later, October 11 1978, two Synanon members placed a de-rattled rattlesnake in the mailbox of attorney Paul Morantz in Pacific Palisades, California. Morantz had successfully brought suit on behalf of a woman abducted by Synanon. The snake bit Morantz but did not kill him.
Six weeks later the Los Angeles Police Department performed a search of the ranch in Badger that turned up a recorded speech by Dederich in which he said, ""We're not going to mess with the old-time, turn-the-other-cheek religious postures ... our religious posture is: Don't mess with us. You can get killed dead, literally dead...these are real threats," he snarls. "They are draining life's blood from us and expecting us to play by their silly rules. We will make the rules. I see nothing frightening about it ... I am quite willing to break some lawyer's legs and next break his wife's legs and threaten to cut their child's arm off. That is the end of that lawyer. That is a very satisfactory, humane way of transmitting information. ... I really do want an ear in a glass of alcohol on my desk."[7]
A drunken Dederich was arrested on December 2. The two other Synanon residents, one of whom was Lance Kenton, son of musician Stan Kenton, pleaded "no contest" to charges of assault and conspiracy to commit murder. While his associates went to jail, Dederich avoided imprisonment by formally stepping down as Chairman of Synanon.
Much of the violence was carried out by a group within Synanon called the "Imperial Marines."
The tiny Point Reyes Light, a weekly newspaper in Marin County, received the Pulitzer Prize for Public Service in 1979 on account of its coverage of Synanon when other news outlets avoided covering the group.
Synanon struggled to survive without its leader and with a severely tarnished reputation. The Internal Revenue Service revoked the group's tax exemption and the properties were confiscated or sold. By the mid-1990s the community had essentially folded.
# Successes
Despite its faults, the Synanon program worked for many individuals. Among other successes, it is credited with curing heroin-addicted jazz musicians Frank Rehak, Joe Pass and Art Pepper (Pepper discusses his Synanon experiences at length in his autobiography Straight Life), and actor Matthew "Stymie" Beard. In 1962 Pass formed a band made up of Synanon patients who recorded an album titled, The Sounds of Synanon. [8] The organization was touted by motivational speaker Florrie Fisher in her speeches to high schoolers, and she credited it with curing her of a heroin addiction. It also inspired more moderate, successful programs such as Delancey Street, co-founded by John Maher, a former Synanon member. Many former members still value the positive aspects of Synanon, primarily its strong sense of community, and remain in close contact, personally or through online chat groups, and some even own businesses together.
A branch of Synanon founded in Germany in 1971 is still in operation.
# Popular depictions
Synanon is referenced in the Bob Dylan song "Lenny Bruce," from his 1981 album Shot of Love. Producer/writer J. Michael Straczynski used a version of the Synanon Game in his Science Fiction series Babylon 5 (episode "Signs and Portents"). The New-Path drug treatment centers in Phillip K. Dick's novel A Scanner Darkly bear numerous similarities to Synanon. | https://www.wikidoc.org/index.php/Synanon | |
a4ceae91270b5383cdc95ef300c1486e421dbef5 | wikidoc | Synemin | Synemin
Synemin, also known as desmuslin, is a protein that in humans is encoded by the SYNM gene. Synemin is an intermediate filament (IF) family member. IF proteins are cytoskeletal proteins that confer resistance to mechanical stress and are encoded by a dispersed multigene family. This protein has been found to form a linkage between desmin, which is a subunit of the IF network, and the extracellular matrix, and provides an important structural support in muscle.
# Function
Synemin is an intermediate filament (IF) and, like other IFs, primarily functions to integrate mechanical stress and maintain structural integrity in eukaryotic cells. While it has been observed in a variety of cell types, it has been best studied in the sarcomere of skeletal myocytes. It localizes at the Z-disk and has been shown to bind to α-dystrobrevin, α-actinin, and desmin to act as a mechanical linker in transmitting force laterally throughout the tissue, especially between the contractile myofibrils and extracellular matrix. Synemin contributes to linkage between costameres and the contractile apparatus in skeletal muscle of synemin null animals.
# Properties
Synemin has properties very similar to the intermediate filament syncoilin. In particular, it binds to α-dystrobrevin in the dystrophin-associated protein complex to act as a mechanical "linker" between the myofibrillar network and the cell membrane.
# Splice variants
Two splice variant isoforms of synemin exist, α and β. Both isoforms have a very short N-terminal domain of 10 amino acids and a long C-terminal domain consisting of 1243 amino acids for the α isoform and 931 amino acids for the β isoform. An intronic sequence of the synemin β isoform is used as a coding sequence for synemin α.
# History
The origin of the synemin/desmuslin naming convention is quite complex. In 1980, synemin was first identified in avian smooth muscle and was initially described as an IF-associated protein due to its colocalization and copurification with desmin and vimentin. Subsequent to the cloning of chicken synemin, Mizuno and colleagues reported the cloning of a novel IF protein, human desmuslin, as an α-dystrobrevin-interacting protein. Sequence analysis showed that human desmuslin was 32% identical and 11% similar to the amino acid sequence of chicken synemin, while the IF proteins vimentin and desmin are more than 80% identical across the same species. Although several parts were very similar between human desmuslin and chicken synemin, the low degree of conservation between these two proteins compared to other cloned IF proteins suggested that synemin was not the human desmuslin orthologue. In addition, unlike chicken synemin, in vitro coimmunoprecipitation assays could not detect an interaction between human desmuslin and α-actinin. In 2001, Titeux and colleagues reported the cloning of the α and β splice-varying isoforms of human synemin and showed that β-synemin was identical to desmuslin. In 2014 was reported the first synemin -/- null animal. | Synemin
Synemin, also known as desmuslin, is a protein that in humans is encoded by the SYNM gene.[1] Synemin is an intermediate filament (IF) family member. IF proteins are cytoskeletal proteins that confer resistance to mechanical stress and are encoded by a dispersed multigene family. This protein has been found to form a linkage between desmin, which is a subunit of the IF network, and the extracellular matrix, and provides an important structural support in muscle.
# Function
Synemin is an intermediate filament (IF) and, like other IFs, primarily functions to integrate mechanical stress and maintain structural integrity in eukaryotic cells. While it has been observed in a variety of cell types, it has been best studied in the sarcomere of skeletal myocytes. It localizes at the Z-disk and has been shown to bind to α-dystrobrevin, α-actinin, and desmin to act as a mechanical linker in transmitting force laterally throughout the tissue, especially between the contractile myofibrils and extracellular matrix. Synemin contributes to linkage between costameres and the contractile apparatus in skeletal muscle of synemin null animals.[2]
# Properties
Synemin has properties very similar to the intermediate filament syncoilin. In particular, it binds to α-dystrobrevin in the dystrophin-associated protein complex to act as a mechanical "linker" between the myofibrillar network and the cell membrane.[3]
# Splice variants
Two splice variant isoforms of synemin exist, α and β. Both isoforms have a very short N-terminal domain of 10 amino acids and a long C-terminal domain consisting of 1243 amino acids for the α isoform and 931 amino acids for the β isoform.[4] An intronic sequence of the synemin β isoform is used as a coding sequence for synemin α.[4]
# History
The origin of the synemin/desmuslin naming convention is quite complex. In 1980, synemin was first identified in avian smooth muscle and was initially described as an IF-associated protein due to its colocalization and copurification with desmin and vimentin.[5] Subsequent to the cloning of chicken synemin, Mizuno and colleagues reported the cloning of a novel IF protein, human desmuslin, as an α-dystrobrevin-interacting protein.[3] Sequence analysis showed that human desmuslin was 32% identical and 11% similar to the amino acid sequence of chicken synemin, while the IF proteins vimentin and desmin are more than 80% identical across the same species. Although several parts were very similar between human desmuslin and chicken synemin, the low degree of conservation between these two proteins compared to other cloned IF proteins suggested that synemin was not the human desmuslin orthologue.[3] In addition, unlike chicken synemin, in vitro coimmunoprecipitation assays could not detect an interaction between human desmuslin and α-actinin.[3] In 2001, Titeux and colleagues reported the cloning of the α and β splice-varying isoforms of human synemin and showed that β-synemin was identical to desmuslin.[4] In 2014 was reported the first synemin -/- null animal.[2] | https://www.wikidoc.org/index.php/Synemin | |
88c821d76ccdb736279fc712d940f98c608df94b | wikidoc | Synulox | Synulox
Synulox® is a widely known brand name of Veterinary Antibiotic, used for treating infections mostly in the lungs, and nasal tract; and as a broad-spectrum antibiotic. The drug is a compound of amoxicillin and Clavulanic Acid. See also Co-amoxiclav.
NB - All quantities shown below are combined - i.e. 500mg = 400mg Amoxicillin and 100mg Clavulanic Acid.
# Formulations
- 500mg Bolus: Large film-coated tablets. For the treatment of enteritis and navel ill in calves.
- Intramammary Suspension: Synulox + Prednisolone for intra-mammary infusion. For the treatment of mastitis in lactating cows.
- Palatable Drops: A powder for reconstitution for oral administration. A broad-spectrum antibiotic for dogs and cats.
- Palatable Tablets: Available as 50mg, 250mg and 500mg for oral administration. A broad-spectrum antibiotic for dogs and cats.
- Synulox Ready-To-Use Injection: Multi-purpose injectable formulation, recommended for respiratory tract infections, soft tissue infections, metritis and mastitis in cattle; respiratory tract infections, colibacillosis and mastitis, metritis & agalactia in pigs; respiratory tract infections, urinary tract infections, skin and soft tissue infections in dogs and cats.
# Bacterial Resistance
Bacterial antibiotic resistance is a growing problem in veterinary medicine. Clavulanic acid inactivates beta-lactamases which are a common resistance strategy in gram positive bacteria.
Synulox is reported to be effective against clinical Klebsiella infections, but is not efficacious against Pseudomonas infections. | Synulox
Synulox® is a widely known brand name of Veterinary Antibiotic, used for treating infections mostly in the lungs, and nasal tract; and as a broad-spectrum antibiotic. The drug is a compound of amoxicillin and Clavulanic Acid. See also Co-amoxiclav.
NB - All quantities shown below are combined - i.e. 500mg = 400mg Amoxicillin and 100mg Clavulanic Acid.
# Formulations
- 500mg Bolus: Large film-coated tablets. For the treatment of enteritis and navel ill in calves.
- Intramammary Suspension: Synulox + Prednisolone for intra-mammary infusion. For the treatment of mastitis in lactating cows.
- Palatable Drops: A powder for reconstitution for oral administration. A broad-spectrum antibiotic for dogs and cats.
- Palatable Tablets: Available as 50mg, 250mg and 500mg for oral administration. A broad-spectrum antibiotic for dogs and cats.
- Synulox Ready-To-Use Injection: Multi-purpose injectable formulation, recommended for respiratory tract infections, soft tissue infections, metritis and mastitis in cattle; respiratory tract infections, colibacillosis and mastitis, metritis & agalactia in pigs; respiratory tract infections, urinary tract infections, skin and soft tissue infections in dogs and cats.
# Bacterial Resistance
Bacterial antibiotic resistance is a growing problem in veterinary medicine.[1] Clavulanic acid inactivates beta-lactamases which are a common resistance strategy in gram positive bacteria.
Synulox is reported to be effective against clinical Klebsiella infections, but is not efficacious against Pseudomonas infections. | https://www.wikidoc.org/index.php/Synulox | |
5f0719c920d7488fde7e8c86ecdd3887456327e5 | wikidoc | TACSTD2 | TACSTD2
Tumor-associated calcium signal transducer 2, also known as Trop-2 and as epithelial glycoprotein-1 antigen (EGP-1), is a protein that in humans is encoded by the TACSTD2 gene.
This intronless gene encodes a carcinoma-associated antigen defined by the monoclonal antibody GA733. This antigen is a member of a family including at least two type I membrane proteins. It transduces an intracellular calcium signal and acts as a cell surface receptor.
Mutations of this gene result in gelatinous drop-like corneal dystrophy, an autosomal recessive disorder characterized by severe corneal amyloidosis leading to blindness.
This antigen is the target of sacituzumab govitecan, an antibody-drug conjugate. | TACSTD2
Tumor-associated calcium signal transducer 2, also known as Trop-2 and as epithelial glycoprotein-1 antigen (EGP-1),[1] is a protein that in humans is encoded by the TACSTD2 gene.[2][3][4]
This intronless gene encodes a carcinoma-associated antigen defined by the monoclonal antibody GA733. This antigen is a member of a family including at least two type I membrane proteins. It transduces an intracellular calcium signal and acts as a cell surface receptor.
Mutations of this gene result in gelatinous drop-like corneal dystrophy, an autosomal recessive disorder characterized by severe corneal amyloidosis leading to blindness.[4]
This antigen is the target of sacituzumab govitecan, an antibody-drug conjugate. | https://www.wikidoc.org/index.php/TACSTD2 | |
132a2a7b10bd1fd3ba926b785dc5ea70b8c5ffc0 | wikidoc | TAK 442 | TAK 442
# TAK in Acute Coronary Syndrome Patients
On October 26, 2010 Takeda announced the top line data from a phase 2 study of TAK-442, an oral anticoagulant, biologically active factor Xa inhibitor (fXai). "This phase 2, multi-center, randomized double blind, placebo-controlled study conducted globally except in Japan was designed to evaluate the safety and tolerability of multiple doses and regimens (10mg BID to 120mg BID) of TAK-442 with placebo in subjects with a recent acute coronary syndrome (ACS) event, in addition to standard treatment (aspirin or dual anti-platelet therapy) for prevention of recurrent ischemic or thromboembolic events."
"The primary safety endpoint was defined as incidence of major bleeding events as defined by the thrombolysis in myocardial infarction (TIMI) scale, which were observed during the 24-week treatment period. In the lower doses there was a low rate of bleeding and in the higher dose groups, the bleeding rates were generally higher than that of placebo."
"The primary efficacy endpoint in the study was a composite of cardiovascular events, consisting of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or myocardial ischemia requiring hospitalization. The study did not demonstrate a positive trend to reduced risk of cardiovascular events for TAK-442 in this ACS patient population, and there was no evidence for a dose-response. Further analyses are underway to better understand the data as well as the possibility of other development strategies. Decisions are expected to be made as soon as the analysis is complete. " | TAK 442
# TAK in Acute Coronary Syndrome Patients
On October 26, 2010 Takeda announced the top line data from a phase 2 study of TAK-442, an oral anticoagulant, biologically active factor Xa inhibitor (fXai)[1]. "This phase 2, multi-center, randomized double blind, placebo-controlled study conducted globally except in Japan was designed to evaluate the safety and tolerability of multiple doses and regimens (10mg BID to 120mg BID) of TAK-442 with placebo in subjects with a recent acute coronary syndrome (ACS) event, in addition to standard treatment (aspirin or dual anti-platelet therapy) for prevention of recurrent ischemic or thromboembolic events."
"The primary safety endpoint was defined as incidence of major bleeding events as defined by the thrombolysis in myocardial infarction (TIMI) scale, which were observed during the 24-week treatment period. In the lower doses there was a low rate of bleeding and in the higher dose groups, the bleeding rates were generally higher than that of placebo."
"The primary efficacy endpoint in the study was a composite of cardiovascular events, consisting of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or myocardial ischemia requiring hospitalization. The study did not demonstrate a positive trend to reduced risk of cardiovascular events for TAK-442 in this ACS patient population, and there was no evidence for a dose-response. Further analyses are underway to better understand the data as well as the possibility of other development strategies. Decisions are expected to be made as soon as the analysis is complete. " | https://www.wikidoc.org/index.php/TAK_442 | |
bfe4b8af08caebee879c802086b619a6b24a3dca | wikidoc | TAS2R10 | TAS2R10
Taste receptor type 2 member 10 is a protein that in humans is encoded by the TAS2R10 gene.
# Function
This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, they respond to bitter tastants. This gene maps to the taste receptor gene cluster on chromosome 12p13.
TAS2R10 is also expressed in the smooth muscle of human airways, along with several other bitter taste receptors. Their activation in these cells causes an increase in intracellular calcium ion, which in turn triggers the opening of potassium channels which hyperpolarize the membrane and cause the smooth muscle to relax. Hence, activation of these receptors leads to bronchodilation. | TAS2R10
Taste receptor type 2 member 10 is a protein that in humans is encoded by the TAS2R10 gene.[1][2][3]
# Function
This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, they respond to bitter tastants. This gene maps to the taste receptor gene cluster on chromosome 12p13.[3]
TAS2R10 is also expressed in the smooth muscle of human airways, along with several other bitter taste receptors. Their activation in these cells causes an increase in intracellular calcium ion, which in turn triggers the opening of potassium channels which hyperpolarize the membrane and cause the smooth muscle to relax. Hence, activation of these receptors leads to bronchodilation.[4] | https://www.wikidoc.org/index.php/TAS2R10 | |
6cca8906fafb612dc865ff0621537a1d300e8f92 | wikidoc | TAS2R14 | TAS2R14
Taste receptor type 2 member 14 is a protein that in humans is encoded by the TAS2R14 gene.
# Function
This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, TAS2R14 responds to (−)-α-thujone, the primary neurotoxic agent in absinthe, and picrotoxin, a poison found in fishberries. This gene maps to the taste receptor gene cluster on chromosome 12p13.
TAS2R14 is also expressed in the smooth muscle of human airways, along with several other bitter taste receptors. Their activation in these cells causes an increase in intracellular calcium ion, which in turn triggers the opening of potassium channels which hyperpolarize the membrane and cause the smooth muscle to relax. Hence, activation of these receptors leads to bronchodilation. | TAS2R14
Taste receptor type 2 member 14 is a protein that in humans is encoded by the TAS2R14 gene.[1][2][3]
# Function
This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, TAS2R14 responds to (−)-α-thujone, the primary neurotoxic agent in absinthe, and picrotoxin, a poison found in fishberries.[4] This gene maps to the taste receptor gene cluster on chromosome 12p13.[3]
TAS2R14 is also expressed in the smooth muscle of human airways, along with several other bitter taste receptors. Their activation in these cells causes an increase in intracellular calcium ion, which in turn triggers the opening of potassium channels which hyperpolarize the membrane and cause the smooth muscle to relax. Hence, activation of these receptors leads to bronchodilation.[5] | https://www.wikidoc.org/index.php/TAS2R14 | |
e4f2f533e268864d30cee2146d4ad0adea4569c7 | wikidoc | TAS2R16 | TAS2R16
TAS2R16 (taste receptor, type 2, member 16) is a human gene that encodes for a receptor that may play a role in the perception of bitterness.
The TAS2R16 gene is located on the long (q) arm of chromosome 7 at position 31.1 - 31.3, from base pair 122,228,764 to base pair 122,229,639.
# Clinical significance
Variants of this gene have been linked to an increased risk for alcohol dependence.
There is an East African origin for high salicin sensitivity, and thus sensitivity to bitterness in people from this region, with this phenotype matched to TAS2R16 variants. | TAS2R16
TAS2R16 (taste receptor, type 2, member 16) is a human gene that encodes for a receptor that may play a role in the perception of bitterness.[1][2]
The TAS2R16 gene is located on the long (q) arm of chromosome 7 at position 31.1 - 31.3, from base pair 122,228,764 to base pair 122,229,639.
# Clinical significance
Variants of this gene have been linked to an increased risk for alcohol dependence.[3]
There is an East African origin for high salicin sensitivity, and thus sensitivity to bitterness in people from this region, with this phenotype matched to TAS2R16 variants.[4] | https://www.wikidoc.org/index.php/TAS2R16 | |
60d326ac9b1d0bd357e3ff02a0d767921e4da733 | wikidoc | TAS2R31 | TAS2R31
Taste receptor, type 2, member 31, also known as TAS2R31, is a protein which in humans is encoded by the TAS2R31 gene. This bitter taste receptor has been shown to respond to saccharin in vitro.
TAS2R31 is also expressed in the smooth muscle of human airways, along with several other bitter taste receptors. Their activation in these cells causes an increase in intracellular calcium ion, which in turn triggers the opening of potassium channels which hyperpolarize the membrane and cause the smooth muscle to relax. Hence, activation of these receptors leads to bronchodilation.
Polymorphisms in this gene have been associated with the perceived bitterness of sweetener acesulfame potassium. | TAS2R31
Taste receptor, type 2, member 31, also known as TAS2R31, is a protein which in humans is encoded by the TAS2R31 gene.[1] This bitter taste receptor has been shown to respond to saccharin in vitro.[2]
TAS2R31 is also expressed in the smooth muscle of human airways, along with several other bitter taste receptors. Their activation in these cells causes an increase in intracellular calcium ion, which in turn triggers the opening of potassium channels which hyperpolarize the membrane and cause the smooth muscle to relax. Hence, activation of these receptors leads to bronchodilation.[3][3]
Polymorphisms in this gene have been associated with the perceived bitterness of sweetener acesulfame potassium.[4] | https://www.wikidoc.org/index.php/TAS2R31 | |
ab262c085fadf542da9a3c71e421e3439643284a | wikidoc | TAS2R38 | TAS2R38
Taste receptor 2 member 38 is a protein that in humans is encoded by the TAS2R38 gene. TAS2R38 is a bitter taste receptor; varying genotypes of TAS2R38 influence the ability to taste both 6-n-propylthiouracil (PROP) and phenylthiocarbamide (PTC). Though it has often been proposed that varying taste receptor genotypes could influence tasting ability, TAS2R38 is one of the only taste receptors shown to have this function.
# Signal transduction
As with all TAS2R proteins, TAS2R38 utilizes the G-protein gustducin as its primary method of signal transduction. Both the α- and βγ-subunits are crucial to the transmission of the taste signal. See: taste receptor.
# PTC sensitivity
Differential ability to taste the bitter compound phenylthiocarbamide (PTC) was discovered more than 80 years ago. Since then, PTC tasting ability has been mapped to chromosome 7q and, several years later, was shown to be directly related to TAS2R38 genotype. There are three common polymorphisms in the TAS2R38 gene—A49P, V262A, and I296V—which combine to form two common haplotypes and several other very rare haplotypes. The two common haplotypes are AVI (often called “nontaster”) and PAV (often called “taster”). Varying combinations of these haplotypes will yield homozygotes—PAV/PAV and AVI/AVI—and heterozygotes—PAV/AVI. These genotypes can account for up to 85% of the variation in PTC tasting ability: people possessing two copies of the PAV polymorphism report PTC to be more bitter than TAS2R38 heterozygotes, and people possessing two copies of the AVI/AVI polymorphism often report PTC as being essentially tasteless. These polymorphisms are hypothesized to affect taste by altering G-protein-binding domains.
Because bitter substances are usually toxic, the presence of a “nontaster” geno- and phenotype seems evolutionarily undesirable. Several studies have suggested, however, that the AVI polymorphism may code for an entirely new receptor which processes a different and as-yet undiscovered bitter compound. Furthermore, the presence of the nontaster allele may reflect the desirability of maintaining a mostly heterozygous population; this group of people may possess flexibility in their bitter taste perception, enabling them to avoid a greater number of toxins than either homozygotic group. Other studies, however, suggest that the AVI nontaster genotype has no functional ligand.
This genotypical alteration of taste phenotype is currently unique to TAS2R38. Though genotype has been proposed as a mechanism for determining individual taste preferences, TAS2R38 is so far the first and only taste receptor to display this property.
# PROP sensitivity, supertasting, and alcoholism
The TAS2R38 protein also confers sensitivity to the bitter compound 6-n-propylthiouracil (PROP). Because perception of PROP bitterness has been associated with supertasting, and because TAS2R38 genotypes associate with PROP-tasting phenotypes, it has been proposed that TAS2R38 genotypes may have a role in supertasting capabilities. It appears that while TAS2R38 genotypes determine a threshold of PROP tasting abilities, the genotypes cannot account for the differences in tasting amongst each threshold group. For example, some PAV/PAV homozygotes perceive PROP to be more bitter than others, and TAS2R38 genotype cannot account for these differences. Furthermore, some heterozygotes may become PROP supertasters (despite a lack of two PAV alleles), indicating overlap between PROP bitterness levels and varying TAS2R38 genotypes. These results illustrate that a mechanism beyond TAS2R38 genotype contributes to supertasting capabilities.
Because fungiform papillae (FP) number varies with PROP bitterness, TAS2R38 genotype was also suspected to alter FP number. Again, however, TAS2R38 genotype could not explain FP alterations. Additionally, FP number was not a strong predictor of PROP bitterness amongst TAS2R38 heterozygotes, indicating, again, a lack of knowledge about the relationship between PROP bitterness, TAS2R38, and supertasting. Research is leaning toward a second receptor with PROP sensitivity that confers supertasting abilities.
PROP bitterness and TAS2R38 genotype have been further examined in relation to alcohol intake. Research has suggested that the level of alcohol consumption may correlate with the level of perceived bitterness of ethanol; those people who find PROP to be more bitter also find the taste of ethanol to be less pleasant. Again, however, correlates between TAS2R38 genotype and the taste of alcohol were not significant: the TAS2R38 genotype could not predict the intensity of alcohol bitterness (though PROP bitterness did correlate with alcohol bitterness). Genotype could predict alcohol intake; those with nontaster alleles were more likely to consume more alcohol over the course of the year. Again, a second genetic factor seems to contribute to these phenomena. A gene altering the density of fungiform papillae may provide this second factor. | TAS2R38
Taste receptor 2 member 38 is a protein that in humans is encoded by the TAS2R38 gene. TAS2R38 is a bitter taste receptor; varying genotypes of TAS2R38 influence the ability to taste both 6-n-propylthiouracil (PROP)[1] and phenylthiocarbamide (PTC).[2][3] Though it has often been proposed that varying taste receptor genotypes could influence tasting ability, TAS2R38 is one of the only taste receptors shown to have this function.[4]
# Signal transduction
As with all TAS2R proteins, TAS2R38 utilizes the G-protein gustducin as its primary method of signal transduction. Both the α- and βγ-subunits are crucial to the transmission of the taste signal.[5] See: taste receptor.
# PTC sensitivity
Differential ability to taste the bitter compound phenylthiocarbamide (PTC) was discovered more than 80 years ago.[6] Since then, PTC tasting ability has been mapped to chromosome 7q[7] and, several years later, was shown to be directly related to TAS2R38 genotype.[2][3][6][7][8] There are three common polymorphisms in the TAS2R38 gene—A49P, V262A, and I296V—which combine to form two common haplotypes and several other very rare haplotypes. The two common haplotypes are AVI (often called “nontaster”) and PAV (often called “taster”). Varying combinations of these haplotypes will yield homozygotes—PAV/PAV and AVI/AVI—and heterozygotes—PAV/AVI.[8] These genotypes can account for up to 85% of the variation in PTC tasting ability: people possessing two copies of the PAV polymorphism report PTC to be more bitter than TAS2R38 heterozygotes, and people possessing two copies of the AVI/AVI polymorphism often report PTC as being essentially tasteless. These polymorphisms are hypothesized to affect taste by altering G-protein-binding domains.[2]
Because bitter substances are usually toxic, the presence of a “nontaster” geno- and phenotype seems evolutionarily undesirable. Several studies have suggested, however, that the AVI polymorphism may code for an entirely new receptor which processes a different and as-yet undiscovered bitter compound.[3][6] Furthermore, the presence of the nontaster allele may reflect the desirability of maintaining a mostly heterozygous population; this group of people may possess flexibility in their bitter taste perception, enabling them to avoid a greater number of toxins than either homozygotic group.[6] Other studies, however, suggest that the AVI nontaster genotype has no functional ligand.[9]
This genotypical alteration of taste phenotype is currently unique to TAS2R38. Though genotype has been proposed as a mechanism for determining individual taste preferences, TAS2R38 is so far the first and only taste receptor to display this property.[4]
# PROP sensitivity, supertasting, and alcoholism
The TAS2R38 protein also confers sensitivity to the bitter compound 6-n-propylthiouracil (PROP). Because perception of PROP bitterness has been associated with supertasting, and because TAS2R38 genotypes associate with PROP-tasting phenotypes, it has been proposed that TAS2R38 genotypes may have a role in supertasting capabilities. It appears that while TAS2R38 genotypes determine a threshold of PROP tasting abilities, the genotypes cannot account for the differences in tasting amongst each threshold group. For example, some PAV/PAV homozygotes perceive PROP to be more bitter than others, and TAS2R38 genotype cannot account for these differences. Furthermore, some heterozygotes may become PROP supertasters (despite a lack of two PAV alleles), indicating overlap between PROP bitterness levels and varying TAS2R38 genotypes. These results illustrate that a mechanism beyond TAS2R38 genotype contributes to supertasting capabilities.[9]
Because fungiform papillae (FP) number varies with PROP bitterness, TAS2R38 genotype was also suspected to alter FP number. Again, however, TAS2R38 genotype could not explain FP alterations. Additionally, FP number was not a strong predictor of PROP bitterness amongst TAS2R38 heterozygotes, indicating, again, a lack of knowledge about the relationship between PROP bitterness, TAS2R38, and supertasting. Research is leaning toward a second receptor with PROP sensitivity that confers supertasting abilities.[9]
PROP bitterness and TAS2R38 genotype have been further examined in relation to alcohol intake. Research has suggested that the level of alcohol consumption may correlate with the level of perceived bitterness of ethanol; those people who find PROP to be more bitter also find the taste of ethanol to be less pleasant. Again, however, correlates between TAS2R38 genotype and the taste of alcohol were not significant: the TAS2R38 genotype could not predict the intensity of alcohol bitterness (though PROP bitterness did correlate with alcohol bitterness). Genotype could predict alcohol intake; those with nontaster alleles were more likely to consume more alcohol over the course of the year. Again, a second genetic factor seems to contribute to these phenomena. A gene altering the density of fungiform papillae may provide this second factor.[1] | https://www.wikidoc.org/index.php/TAS2R38 | |
d701a14f10419dcbbb7ab7c1d32cf74e53741cda | wikidoc | TBC1D24 | TBC1D24
TBC1 domain family, member 24 is a protein that in humans is encoded by the TBC1D24 gene.
# Function
This gene encodes a protein with a conserved domain, referred to as the TBC domain, characteristic of proteins which interact with GTPases. TBC domain proteins may serve as GTPase-activating proteins for a particular group of GTPases, the Rab (Ras-related proteins in brain) small GTPases which are involved in the regulation of membrane trafficking. Mutations in this gene are associated with familial infantile myoclonic epilepsy. Alternative splicing results in multiple transcript variants.
Mutations in TBC1D24 cause Hereditary hearing loss . | TBC1D24
TBC1 domain family, member 24 is a protein that in humans is encoded by the TBC1D24 gene.[1]
# Function
This gene encodes a protein with a conserved domain, referred to as the TBC domain, characteristic of proteins which interact with GTPases. TBC domain proteins may serve as GTPase-activating proteins for a particular group of GTPases, the Rab (Ras-related proteins in brain) small GTPases which are involved in the regulation of membrane trafficking. Mutations in this gene are associated with familial infantile myoclonic epilepsy. Alternative splicing results in multiple transcript variants.
Mutations in TBC1D24 cause Hereditary hearing loss .[2] | https://www.wikidoc.org/index.php/TBC1D24 | |
0558843ecfb7bcfc7afb647d32287848cc8efd1a | wikidoc | TBL1XR1 | TBL1XR1
F-box-like/WD repeat-containing protein TBL1XR1 is a protein that in humans is encoded by the TBL1XR1 gene.
The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation. Mutations in TBL1XR1 have been identified in lymphomas, including MYD88 wild-type Waldenstrom's Macroglobulinemia
# Interactions
TBL1XR1 has been shown to interact with Nuclear receptor co-repressor 1. | TBL1XR1
F-box-like/WD repeat-containing protein TBL1XR1 is a protein that in humans is encoded by the TBL1XR1 gene.[1][2][3]
The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation.[3] Mutations in TBL1XR1 have been identified in lymphomas, including MYD88 wild-type Waldenstrom's Macroglobulinemia[4]
# Interactions
TBL1XR1 has been shown to interact with Nuclear receptor co-repressor 1.[2][5][6] | https://www.wikidoc.org/index.php/TBL1XR1 | |
c57c28db7bdb751d51a4684127838bcb9e3d74a9 | wikidoc | TIMMDC1 | TIMMDC1
TIMMDC1 is a protein that in humans is encoded by the TIMMDC1 gene. It is a chaperone protein involved in constructing the membrane arm of mitochondrial Complex I. A frameshift mutation in an intron of this gene has been shown to cause failure to thrive, retardation of psychomotor development, infantile-onset hypotonia, and severe neurologic dysfunction. High expression of this gene has been associated with migration of lung cancer cells while depletion of the protein has been shown to affect regulation of apoptosis, the cell cycle, and cell migration.
# Structure
The TIMMDC1 gene is located on the q arm of chromosome 3 in position 13.33 and spans 25,760 base pairs, with 7 exons. The gene produces a 32.2 kDa protein composed of 285 amino acids. The TIMMDC1 protein has 4 transmembrane domains, with the N-terminal and C-terminal extensions localized in the mitochondrial matrix. TIMMDC1 is a multipass mitochondrial inner membrane protein, predicted to be a member of the 4-pass transmembrane protein family of TIM17-TIM22-TIM23. Its topology is predicted to be analogous to TIMM23.
# Function
TIMMDC1 is a chaperone protein involved in the assembly of the mitochondrial Complex I (NADH-ubiquinone oxidoreductase), participating in the construction of the membrane arm of complex I.
# Clinical Significance
A frameshift mutation in intron 5 of the TIMMDC1 gene has been shown to cause severe neurologic dysfunction, infantile-onset hypotonia, retardation of psychomotor development, and failure to thrive. Additionally, high expression of TIMMDC1 has been associated with metastasis of lung carcinoma cells, with depletion of the protein inhibiting growth and migration of 95D lung carcinoma cells. Depletion of TIMMDC1 has also been shown to alter expression of genes involved in the regulation of apoptosis, cell-cycle arrest, and cell migration, including CCNG2, PTEN, TIMP3, and COL3A1.
# Interactions
The TIMMDC1 protein interacts with the intermediate 315 kDa subcomplex of incompletely assembled complex I and has interactions with FATE1, in addition to about 60 other proteins. TIMMDC1 associates reciprocally with multiple components of the ECSIT-TMEM126B-ACAD9-NDUFAF1 assembly factor complex (MCIA complex). | TIMMDC1
TIMMDC1 is a protein that in humans is encoded by the TIMMDC1 gene.[1][2] It is a chaperone protein involved in constructing the membrane arm of mitochondrial Complex I.[3] A frameshift mutation in an intron of this gene has been shown to cause failure to thrive, retardation of psychomotor development, infantile-onset hypotonia, and severe neurologic dysfunction.[4] High expression of this gene has been associated with migration of lung cancer cells while depletion of the protein has been shown to affect regulation of apoptosis, the cell cycle, and cell migration.[5]
# Structure
The TIMMDC1 gene is located on the q arm of chromosome 3 in position 13.33 and spans 25,760 base pairs, with 7 exons.[2] The gene produces a 32.2 kDa protein composed of 285 amino acids.[6][7] The TIMMDC1 protein has 4 transmembrane domains, with the N-terminal and C-terminal extensions localized in the mitochondrial matrix. TIMMDC1 is a multipass mitochondrial inner membrane protein, predicted to be a member of the 4-pass transmembrane protein family of TIM17-TIM22-TIM23. Its topology is predicted to be analogous to TIMM23.[8]
# Function
TIMMDC1 is a chaperone protein involved in the assembly of the mitochondrial Complex I (NADH-ubiquinone oxidoreductase), participating in the construction of the membrane arm of complex I.[3]
# Clinical Significance
A frameshift mutation in intron 5 of the TIMMDC1 gene has been shown to cause severe neurologic dysfunction, infantile-onset hypotonia, retardation of psychomotor development, and failure to thrive.[4] Additionally, high expression of TIMMDC1 has been associated with metastasis of lung carcinoma cells, with depletion of the protein inhibiting growth and migration of 95D lung carcinoma cells. Depletion of TIMMDC1 has also been shown to alter expression of genes involved in the regulation of apoptosis, cell-cycle arrest, and cell migration, including CCNG2, PTEN, TIMP3, and COL3A1.[5]
# Interactions
The TIMMDC1 protein interacts with the intermediate 315 kDa subcomplex of incompletely assembled complex I and has interactions with FATE1, in addition to about 60 other proteins.[9][3] TIMMDC1 associates reciprocally with multiple components of the ECSIT-TMEM126B-ACAD9-NDUFAF1 assembly factor complex (MCIA complex).[8] | https://www.wikidoc.org/index.php/TIMMDC1 | |
82d949ef85170cbd866622299bc4f622271d8c74 | wikidoc | TLQP-62 | TLQP-62
TLQP-62 (amino acid 556-617) is a VGF-derived C-terminal peptide that was first discovered by Trani et al. TLQP-62 is derived from VGF precursor protein via proteolytic cleavage by prohormone convertases PC1/3 at the RPR555 site. TLQP-62 is named after its first four N-terminal amino acids and its peptide length.
# Function
Although the receptor(s) for TLQP-62 has not been identified so far, extensive studies have demonstrated that it acts on central nervous system, peripheral nervous system and endocrine tissue to exert its biological functions.
## Synaptic plasticity
Acute TLQP-62 treatment rapidly increases synaptic activity in hippocampal neurons, and potentiates CA1 field excitatory postsynaptic potential fEPSP in the hippocampal slices, thus facilitating hippocampal synaptic transmission. TLQP-62 also increases dendritic branching and length in cultured hippocampal neurons.
## Neurogenesis
TLQP-62 treatment enhances hippocampal neurogenesis both in vitro and in vivo by promoting the proliferation in neuronal progenitor cells.
## Antidepressant efficacy
Intrahippocampal TLQP-62 infusion produces both rapid and sustained antidepressant-like effects in the forced swim test. TLQP-62's processed peptide AQEE-30, when given via intracerebroventricular route, also elicits antidepressant-like effects.
## Memory and learning
Acute intrahippocampal TLQP-62 infusion enhances memory formation via BDNF/TrkB signaling.
## Pain
Acute intrathecal administration of TLQP-62 induces hypersensitivity to mechanical and cold stimuli that recapitulates neuropathic pain, potentially by regulating the excitability of dorsal horn neurons.
## Insulin secretion
TLQP-62 treatment increases insulin secretion in cultured insulinoma cells by increasing intracellular calcium mobilization. | TLQP-62
TLQP-62 (amino acid 556-617) is a VGF-derived C-terminal peptide that was first discovered by Trani et al.[1] TLQP-62 is derived from VGF precursor protein via proteolytic cleavage by prohormone convertases PC1/3 at the RPR555 site.[2] TLQP-62 is named after its first four N-terminal amino acids and its peptide length.
# Function
Although the receptor(s) for TLQP-62 has not been identified so far, extensive studies have demonstrated that it acts on central nervous system, peripheral nervous system and endocrine tissue to exert its biological functions.
## Synaptic plasticity
Acute TLQP-62 treatment rapidly increases synaptic activity in hippocampal neurons,[3] and potentiates CA1 field excitatory postsynaptic potential fEPSP in the hippocampal slices,[4] thus facilitating hippocampal synaptic transmission. TLQP-62 also increases dendritic branching and length in cultured hippocampal neurons.[5]
## Neurogenesis
TLQP-62 treatment enhances hippocampal neurogenesis both in vitro and in vivo[6] by promoting the proliferation in neuronal progenitor cells.[7]
## Antidepressant efficacy
Intrahippocampal TLQP-62 infusion produces both rapid and sustained antidepressant-like effects in the forced swim test.[8][9] TLQP-62's processed peptide AQEE-30, when given via intracerebroventricular route, also elicits antidepressant-like effects.[10]
## Memory and learning
Acute intrahippocampal TLQP-62 infusion enhances memory formation via BDNF/TrkB signaling.[11]
## Pain
Acute intrathecal administration of TLQP-62 induces hypersensitivity to mechanical and cold stimuli that recapitulates neuropathic pain, potentially by regulating the excitability of dorsal horn neurons.[12]
## Insulin secretion
TLQP-62 treatment increases insulin secretion in cultured insulinoma cells by increasing intracellular calcium mobilization.[13] | https://www.wikidoc.org/index.php/TLQP-62 | |
07d5cb97a3d6bb3d37902e46b938d5d0001e00c5 | wikidoc | TMEM131 | TMEM131
Transmembrane protein 131 (TMEM131) is a protein that is encoded by the TMEM131 gene in humans. The TMEM131 protein contains three domains of unknown function 3651 (DUF3651) and two transmembrane domains. This protein has been implicated has having a role in T cell function and development. TMEM131 also resides in a locus (2q11.1) that is associated with Nievergelt's Syndrome when deleted.
# Role In T Cell Function
TMEM131 has been shown to exhibit hypermethylation in patients with Down Syndrome. The authors of this study proposed that, given TMEM131s supposed function in T cell development and function, this hypermethylation may play a role in the suppressed immune function in patients with Down Syndrome.
TMEM131 has also been shown to be up-regulated during the development and differentiation of T cells, and has been shown to have relatively high levels of expression in T cells relative to other tissue types.
# Gene
## Overview
TMEM131 is located on the negative DNA strand (see Sense) of chromosome 2 from 98,372,799 - 98,612,354. The gene product is a 6,657 base pair mRNA with 41 predicted exons in the human gene. Ensembl predicts ten alternative splice forms, four of which are protein coding.
Promoter prediction and analysis was carried out using El Dorado through the Genomatix software page. The predicted promoter region spans 1002 base pairs from 98,611,892 through 98,612,893 on the minus strand of chromosome 2. The program predicted two potential transcriptional start locations. The first spans 216 base pairs from 98,612,501 through 98,612,716. The second spans 182 base pairs from 98,612,262 through 98,612,443.
## Gene Neighborhood
TMEM131 is located directly adjacent to the ZAP70 gene (98,330,331 - 98,356,323) on the positive DNA strand, as well as numerous pseudogenes at the 2q11.2 locus. A Von Willebrand factor containing gene (VWA3B) is located upstream from TMEM131 on the positive strand (98,703,595 - 98,929,410).
## Gene Expression
TMEM131 is expressed in low to moderate levels throughout most of the body, with slightly increased levels occurring in the lymph nodes, uterus and T cells. Expression data in developing fruit fly embryos is available from the BDGP in situ homepage.
# Protein
## Properties/Characteristics
The primary function of the TMEM131 protein is not well understood. The human form has 1883 amino acid residues, with an isoelectric point of 8.74 and a molecular mass of 205,100 Daltons. It has been shown to contain two transmembrane domains at residues 1,091-1,111 and 1,118-1,138. Three DUF3651 regions are located on the N-terminal side of the two adjacent transmembrane domains. These are located at residues 173-245, 502-582, and 639-708. The intercellular location of the protein has not been experimentally determined, but it is thought to reside in either the plasma membrane or endoplasmic reticulum, with each domain on both the N-terminal and C-terminal sides of the transmembrane regions being cytosolic. It contains numerous phosphorylation sites which have been shown both experimentally and with bioinformatic tools. Bioinformatic analysis of the protein using the NetPhos tool predicted 145 potential phosphorylation sites throughout the entire length of the protein.
## Protein Interactions
Protein interaction analysis for TMEM131 has been carried out using computational tools. No interactions were identified through the MINT database. A STRING search revealed ten possible protein interactions through text mining, although none of these should be considered actual protein-protein interactions. Closer analysis of the results shows very little potential for these predictions to be real. The IntAct tool was also used, and this revealed a potential interaction had been found with Superoxide dismutase 2 (SOD2), which had been identified in a yeast Two-hybrid screening study.
# Conservation
## Orthologs
TMEM131 is conserved throughout all of its orthologs. The entire protein is highly conserved in primate orthologs, while conservation is high within the DUF3651 and transmembrane regions in the more distant homologs.
Orthologs were found in species as distantly related to Humans as the Choanoflagellate Monosiga brevicollis using BLAST and the ALIGN tool through the San Diego Super Computer Biology Workbench. The following table gives information on the homologs of TMEM131.
## Paralog
TMEM131 has a single paralog, TMEM131L or KIAA0922. This gene is very similar to TMEM131, but it does not include the second two of the three DUF3651 regions. | TMEM131
Transmembrane protein 131 (TMEM131) is a protein that is encoded by the TMEM131 gene in humans.[1] The TMEM131 protein contains three domains of unknown function 3651 (DUF3651)[2] and two transmembrane domains.[1] This protein has been implicated has having a role in T cell function and development.[3][4] TMEM131 also resides in a locus (2q11.1) that is associated with Nievergelt's Syndrome when deleted.[5]
# Role In T Cell Function
TMEM131 has been shown to exhibit hypermethylation in patients with Down Syndrome.[3] The authors of this study proposed that, given TMEM131s supposed function in T cell development and function, this hypermethylation may play a role in the suppressed immune function in patients with Down Syndrome.
TMEM131 has also been shown to be up-regulated during the development and differentiation of T cells,[4] and has been shown to have relatively high levels of expression in T cells relative to other tissue types.[6]
# Gene
## Overview
TMEM131 is located on the negative DNA strand (see Sense) of chromosome 2 from 98,372,799 - 98,612,354.[8] The gene product is a 6,657 base pair mRNA with 41 predicted exons in the human gene.[1] Ensembl predicts ten alternative splice forms, four of which are protein coding.[9]
Promoter prediction and analysis was carried out using El Dorado[7] through the Genomatix software page.[10] The predicted promoter region spans 1002 base pairs from 98,611,892 through 98,612,893 on the minus strand of chromosome 2. The program predicted two potential transcriptional start locations. The first spans 216 base pairs from 98,612,501 through 98,612,716. The second spans 182 base pairs from 98,612,262 through 98,612,443.
## Gene Neighborhood
TMEM131 is located directly adjacent to the ZAP70 gene (98,330,331 - 98,356,323) on the positive DNA strand, as well as numerous pseudogenes at the 2q11.2 locus. A Von Willebrand factor containing gene (VWA3B) is located upstream from TMEM131 on the positive strand (98,703,595 - 98,929,410).[8]
## Gene Expression
TMEM131 is expressed in low to moderate levels throughout most of the body, with slightly increased levels occurring in the lymph nodes, uterus and T cells.[6] Expression data in developing fruit fly embryos is available from the BDGP in situ homepage.[11]
# Protein
## Properties/Characteristics
The primary function of the TMEM131 protein is not well understood. The human form has 1883 amino acid residues, with an isoelectric point of 8.74 and a molecular mass of 205,100 Daltons.[12] It has been shown to contain two transmembrane domains at residues 1,091-1,111 and 1,118-1,138. Three DUF3651 regions are located on the N-terminal side of the two adjacent transmembrane domains. These are located at residues 173-245, 502-582, and 639-708. The intercellular location of the protein has not been experimentally determined, but it is thought to reside in either the plasma membrane or endoplasmic reticulum, with each domain on both the N-terminal and C-terminal sides of the transmembrane regions being cytosolic.[13] It contains numerous phosphorylation sites which have been shown both experimentally and with bioinformatic tools.[1][12] Bioinformatic analysis of the protein using the NetPhos tool[14] predicted 145 potential phosphorylation sites throughout the entire length of the protein.[15]
## Protein Interactions
Protein interaction analysis for TMEM131 has been carried out using computational tools. No interactions were identified through the MINT database.[16] A STRING search revealed ten possible protein interactions through text mining, although none of these should be considered actual protein-protein interactions.[17] Closer analysis of the results shows very little potential for these predictions to be real. The IntAct tool was also used, and this revealed a potential interaction had been found with Superoxide dismutase 2 (SOD2), which had been identified in a yeast Two-hybrid screening study.[18]
# Conservation
## Orthologs
TMEM131 is conserved throughout all of its orthologs. The entire protein is highly conserved in primate orthologs, while conservation is high within the DUF3651 and transmembrane regions in the more distant homologs.[19]
Orthologs were found in species as distantly related to Humans as the Choanoflagellate Monosiga brevicollis using BLAST[20] and the ALIGN tool through the San Diego Super Computer Biology Workbench.[12] The following table gives information on the homologs of TMEM131.
## Paralog
TMEM131 has a single paralog, TMEM131L or KIAA0922.[32] This gene is very similar to TMEM131, but it does not include the second two of the three DUF3651 regions. | https://www.wikidoc.org/index.php/TMEM131 | |
f3f911776c12d3f0173b05ae735a74f22a6d98ae | wikidoc | TMEM239 | TMEM239
Within mammalia, TMEM239 orthologs are found in organisms belonging to eutheria and metatheria, but not prototheria. No human paralogs for TMEM239 have been identified.
# Expression
Based on human expressed sequence tag (EST) profiles, TMEM239 appears to be expressed in the testis and the brain. According to PaxDb, the abundance of TMEM239 falls within the bottom 10% relative to all other proteins in both mice and humans. Overall, expression of TMEM239 is limited. TMEM239 appears to be expressed at moderate levels in the testes, with low expression in a variety of other tissues, including the brain and submaxillary gland.
# Interactions
TMEM239 protein interactions appear to be implicated in cell signaling, membrane transport and immunology. Human T-cell leukemia virus type-1 Protein TAX-1 (TAX) and Beta-2-microglobulin (B2M) were found to interact with TMEM239 through a host-pathogen yeast two hybrid screen.
Additional TMEM239 protein interactions were identified through a human interactome mapping project. Synthenein-1 (SDCBP) is involved in the trafficking of transmembrane proteins, in addition to neuro and immunomodulation, exosome biogenesis and tumorigenesis. SDCBP is regulated by TGFB1-mediated SMAD2/3. A number of other cell signaling proteins physically associated with TMEM239, including Cyclic AMP-dependent transcription factor (ATF-7), FYVE, RhoGEF and PH domain-containing protein 2 (FGD2) and Syndecan binding protein (SDCBP).
The Golgi SNAP receptor complex member 1 (GOS1) was found to associate with TMEM239. A member of the super-family of proteins called t-SNAREs, GOS1 mediates transport from the ER to the Golgi apparatus. Lastly, the protein Alpha-N-methyltransferease (TAE1) was found to interact with TMEM239. TAE1 catalyzes the methylation of alpha-amino groups of Alanine or Serine residues in -Pro-Lys motifs and Pro-Pro-Lys motifs. TAE1 is also responsible for methylating a number of ribosomal proteins.
# Clinical significance
SNP rs7360412, located in the 3’UTR of TMEM239, was identified in a genome-wide association study of quantitative phenotypes for bipolar disorder as a top marker for fractional anisotropy. In this context, fractional anisotropy, as detected by diffusion tensor imaging, was used to assess white matter integrity. White matter integrity is highly heritable and reduced in both bipolar patients and their unaffected relatives.
RNA-seq was used to analyze the transcriptomes of human and Leishmania primary cutaneous lesions, in order to understand differences in host and parasitic factors influencing the progression of Localized Cutaneous Leishmaniasis (LCL) to Mucosal Leishmaniasis (ML). Decreased expression of TMEM239 in a primary cutaneous lesions indicates a higher probability of ML development. | TMEM239
Within mammalia, TMEM239 orthologs are found in organisms belonging to eutheria and metatheria, but not prototheria. No human paralogs for TMEM239 have been identified.
# Expression
Based on human expressed sequence tag (EST) profiles, TMEM239 appears to be expressed in the testis and the brain.[1] According to PaxDb, the abundance of TMEM239 falls within the bottom 10% relative to all other proteins in both mice and humans.[2] Overall, expression of TMEM239 is limited. TMEM239 appears to be expressed at moderate levels in the testes, with low expression in a variety of other tissues, including the brain and submaxillary gland.
# Interactions
TMEM239 protein interactions appear to be implicated in cell signaling, membrane transport and immunology. Human T-cell leukemia virus type-1 Protein TAX-1 (TAX) and Beta-2-microglobulin (B2M) were found to interact with TMEM239 through a host-pathogen yeast two hybrid screen.[3]
Additional TMEM239 protein interactions were identified through a human interactome mapping project. Synthenein-1 (SDCBP) is involved in the trafficking of transmembrane proteins, in addition to neuro and immunomodulation, exosome biogenesis and tumorigenesis.[4] SDCBP is regulated by TGFB1-mediated SMAD2/3. A number of other cell signaling proteins physically associated with TMEM239, including Cyclic AMP-dependent transcription factor (ATF-7), FYVE, RhoGEF and PH domain-containing protein 2 (FGD2) and Syndecan binding protein (SDCBP).
The Golgi SNAP receptor complex member 1 (GOS1) was found to associate with TMEM239.[5] A member of the super-family of proteins called t-SNAREs, GOS1 mediates transport from the ER to the Golgi apparatus.[6] Lastly, the protein Alpha-N-methyltransferease (TAE1) was found to interact with TMEM239. TAE1 catalyzes the methylation of alpha-amino groups of Alanine or Serine residues in [Ala/Ser]-Pro-Lys motifs and Pro-Pro-Lys motifs. TAE1 is also responsible for methylating a number of ribosomal proteins.[7]
# Clinical significance
SNP rs7360412, located in the 3’UTR of TMEM239, was identified in a genome-wide association study of quantitative phenotypes for bipolar disorder as a top marker for fractional anisotropy.[8] In this context, fractional anisotropy, as detected by diffusion tensor imaging, was used to assess white matter integrity. White matter integrity is highly heritable and reduced in both bipolar patients and their unaffected relatives.
RNA-seq was used to analyze the transcriptomes of human and Leishmania primary cutaneous lesions, in order to understand differences in host and parasitic factors influencing the progression of Localized Cutaneous Leishmaniasis (LCL) to Mucosal Leishmaniasis (ML).[9] Decreased expression of TMEM239 in a primary cutaneous lesions indicates a higher probability of ML development. | https://www.wikidoc.org/index.php/TMEM239 | |
e8281973d7e3f50139fa02b79f59847c53a5955a | wikidoc | TMEM241 | TMEM241
Transmembrane protein 241 (aka C18orf45, hVVT) is a ubiquitous sugar transporter protein which in humans is encoded by the TMEM241 gene.
# Gene
In humans, TMEM241 is a 142,188 bp gene located at 18q11.2 which contains 24 exons.
## Gene Neighborhood
TMEM241 is located near CABLES1, RIOK3, and NPC1 on chromosome 18.
# mRNA
The primary mRNA for human TMEM241, isoform 1, contains a 5' UTR hairpin loop conserved in primates.The primary mRNA for human TMEM241 isoform 1 contains binding sites in its 3' UTR for the miRNAs 520f-5p, 378a-5p, and 6866-5p.
# Protein
## General Properties
There are over 10 transcript variants predicted for the human TMEM241 gene found on BLAST. TMEM241 Isoform 1 is approximately 31 kDa in mass. The protein has an isoelectric point of 8.7. and is particularly rich in the amino acid phenylalanine, containing twice the normal proportion of this amino acid.
## Conserved Domains
TMEM241 is composed of 9 transmembrane domains forming a hydrophobic integral component of the membrane composed primarily of alpha helices. TMEM241 contains a VRG4 (Vandate Resistance Glycosylation) domain with homology to the sugar transporter domain VRG4 from Saccharomyces cerevisiae (yeast).
## Post-Translational Modification
TMEM241 is predicted to undergo various phosphorylations, glycation, palmitoylation. For example, TMEM241 isoform 1 has a phosphorylation sites on S6, 64, 170, 177, 291, 295 and 296; glycation sites on K125, 169 and 172; palmitoylation sites on C13, 15, 221.
## Interacting Proteins
There is some evidence that this protein may interact with keratin filament based on a two hybrid screen with the keratin protein KRT40.
# Expression
TMEM241 is likely to be expressed in all tissues at varying levels from basal to moderate expression. Some studies have found changes in the expression of TMEM241. For instance, in cases of acute megakaryoblastic leukemia, TMEM241 was found to be one of the most upregulated genes. In another case TMEM241 was found to be upregulated during the unfolded protein response following the overexpression of Ero1α (Endoplasmic Reticulum oxidoreduclin 1α).
# Homology
TMEM241 is conserved throughout eukaryotes.
## Orthologs
TMEM241 is conserved across all animals and homologs are found throughout eukaryotes. TMEM241 has 19% global identity and 60% identity to GDP-mannose transporter from S. cerevisiae, which contains the VRG4 domain. It is likely that TMEM241 is a GDP-mannose transporter due to this similarity. The graph on the right shows the relative level of conservation of TMEM241 across many species of organism using the principle of a Molecular Clock.
## Paralogs
TMEM241 has two paralogs in humans which have homologs throughout eukaryotes, UGTREL8 and UGTREL7. TMEM241, UGTREL8 and UGTREL7 are a family of sugar transport proteins with close identity to the GDP-mannose transporter identified in S. cerevisiae. | TMEM241
Transmembrane protein 241 (aka C18orf45, hVVT) is a ubiquitous sugar transporter protein which in humans is encoded by the TMEM241 gene.[1]
# Gene
In humans, TMEM241 is a 142,188 bp gene located at 18q11.2 which contains 24 exons.[2]
## Gene Neighborhood
TMEM241 is located near CABLES1, RIOK3, and NPC1 on chromosome 18.[3]
# mRNA
The primary mRNA for human TMEM241, isoform 1,[3] contains a 5' UTR hairpin loop conserved in primates.The primary mRNA for human TMEM241 isoform 1 contains binding sites in its 3' UTR for the miRNAs 520f-5p, 378a-5p, and 6866-5p.[4]
# Protein
## General Properties
There are over 10 transcript variants predicted for the human TMEM241 gene found on BLAST. TMEM241 Isoform 1 is approximately 31 kDa in mass. The protein has an isoelectric point of 8.7. and is particularly rich in the amino acid phenylalanine, containing twice the normal proportion of this amino acid.[5]
## Conserved Domains
TMEM241 is composed of 9 transmembrane domains forming a hydrophobic integral component of the membrane[2] composed primarily of alpha helices.[6][7][8] TMEM241 contains a VRG4 (Vandate Resistance Glycosylation[9]) domain with homology to the sugar transporter domain VRG4 from Saccharomyces cerevisiae (yeast).[10]
## Post-Translational Modification
TMEM241 is predicted to undergo various phosphorylations,[11] glycation,[11] palmitoylation.[12] For example, TMEM241 isoform 1[13] has a phosphorylation sites on S6, 64, 170, 177, 291, 295 and 296;[11] glycation sites on K125, 169 and 172;[11] palmitoylation sites on C13, 15, 221.[12]
## Interacting Proteins
There is some evidence that this protein may interact with keratin filament based on a two hybrid screen with the keratin protein KRT40.[14]
# Expression
TMEM241 is likely to be expressed in all tissues at varying levels from basal to moderate expression.[15] Some studies have found changes in the expression of TMEM241. For instance, in cases of acute megakaryoblastic leukemia, TMEM241 was found to be one of the most upregulated genes.[16] In another case TMEM241 was found to be upregulated during the unfolded protein response following the overexpression of Ero1α (Endoplasmic Reticulum oxidoreduclin 1α).[10]
# Homology
TMEM241 is conserved throughout eukaryotes.
## Orthologs
TMEM241 is conserved across all animals and homologs are found throughout eukaryotes. TMEM241 has 19% global identity and 60% identity to GDP-mannose transporter from S. cerevisiae, which contains the VRG4 domain. It is likely that TMEM241 is a GDP-mannose transporter due to this similarity. The graph on the right shows the relative level of conservation of TMEM241 across many species of organism using the principle of a Molecular Clock.
## Paralogs
TMEM241 has two paralogs in humans which have homologs throughout eukaryotes, UGTREL8[20] and UGTREL7.[21] TMEM241, UGTREL8 and UGTREL7 are a family of sugar transport proteins with close identity to the GDP-mannose transporter identified in S. cerevisiae. | https://www.wikidoc.org/index.php/TMEM241 | |
7178f02d04b6829a4b7618dcc8fd3b8558140506 | wikidoc | TMEM242 | TMEM242
Transmembrane protein 242 (TMEM242) is a protein that in humans is encoded by the TMEM242 gene.
This protein contains a DUF1358 domain (Domain of Unknown Function 1358).
# Domain
The TMEM242 protein has a conserved domain of unknown function pfam 07096, DUF 1358., which covers the first 121 aa of the protein. This domain is conserved in eukaryotes.
# Associated Proteins
Several predicted interacting proteins and functional sites on the protein have been identified. One of the predicted interacting protein is MAP2K1IP1, which is a scaffold protein. This protein is known to be involved in the MAP Kinase pathway. The MAP Kinase pathway is associated with the Alzheimer's pathway through a protein called Tau or MAPT. Excessive phosphorylation of this protein leads to aggregation of neurons which can cause Alzheimer's disease. | TMEM242
Transmembrane protein 242 (TMEM242) is a protein that in humans is encoded by the TMEM242 gene.[1]
This protein contains a DUF1358 domain (Domain of Unknown Function 1358).[2]
# Domain
The TMEM242 protein has a conserved domain of unknown function pfam 07096, DUF 1358., which covers the first 121 aa of the protein. This domain is conserved in eukaryotes.
# Associated Proteins
Several predicted interacting proteins and functional sites on the protein have been identified. One of the predicted interacting protein is MAP2K1IP1, which is a scaffold protein.[3] This protein is known to be involved in the MAP Kinase pathway. The MAP Kinase pathway is associated with the Alzheimer's pathway through a protein called Tau or MAPT. Excessive phosphorylation of this protein leads to aggregation of neurons which can cause Alzheimer's disease. | https://www.wikidoc.org/index.php/TMEM242 |
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