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bc1dbe9eba69604ee385d78926d8327196a69729 | wikidoc | ADAMTS5 | ADAMTS5
A disintegrin and metalloproteinase with thrombospondin motifs 5 also known as ADAMTS5 is an enzyme that in humans is encoded by the ADAMTS5 gene.
# Function
ADAMTS5 is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The enzyme encoded by this gene contains two C-terminal TS motifs and functions as aggrecanase to cleave aggrecan, a major proteoglycan of cartilage. ADAMTS5 may also have a role in the pathogenesis of human osteoarthritis.
# Animal studies
Genetically modified mice in which the catalytic domain of ADAMTS5 was deleted are resistant to cartilage destruction in an experimental model of osteoarthritis. ADAMTS5 is the major aggrecanase in mouse cartilage in a mouse model of inflammatory arthritis. | ADAMTS5
A disintegrin and metalloproteinase with thrombospondin motifs 5 also known as ADAMTS5 is an enzyme that in humans is encoded by the ADAMTS5 gene.[1][2]
# Function
ADAMTS5 is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The enzyme encoded by this gene contains two C-terminal TS motifs and functions as aggrecanase to cleave aggrecan, a major proteoglycan of cartilage.[3] ADAMTS5 may also have a role in the pathogenesis of human osteoarthritis.[4]
# Animal studies
Genetically modified mice in which the catalytic domain of ADAMTS5 was deleted are resistant to cartilage destruction in an experimental model of osteoarthritis.[5] ADAMTS5 is the major aggrecanase in mouse cartilage in a mouse model of inflammatory arthritis.[6] | https://www.wikidoc.org/index.php/ADAMTS5 | |
4c00827f32330b7a0e4d350029b33dce10d46105 | wikidoc | ADAMTS7 | ADAMTS7
A disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS7) is an enzyme that in humans is encoded by the ADAMTS7 gene on chromosome 15. It is ubiquitously expressed in many tissues and cell types. This enzyme catalyzes the degradation of cartilage oligomeric matrix protein (COMP) degradation. ADAMTS7 has been associated with cancer and arthritis in multiple tissue types. The ADAMTS7 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.
# Structure
## Gene
The ADAMTS7 gene resides on chromosome 15 at the band 15q24.2 and contains 25 exons.
## Protein
This 1686-amino acid protein belongs to the ADAMTS family and is one of 19 members known in humans. As an ADAMTS protein, ADAMTS7 contains a shared proteinase domain and an ancillary domain. The proteinase domain can be further divided into a signal peptide, a prodomain, a metalloproteinase domain, and a disintegrin-like domain. In particular, the metalloproteinase domain contains a cysteine-switch motif in its binding site for binding the catalytic zinc ion (Zn2+). A pharmacophore model consisting of four hydrogen bond donor sites and three hydrogen bond acceptor sites was proposed for this domain. Unlike the proteinase domain, the ancillary domain varies by ADAMTS protein and includes any number of thrombospondin (TSP) type 1 motifs, one cysteine-rich and spacer domain, and other domains specific to certain ADAMTS proteins. ADAMTS7 in particular possesses 8 TSP type 1 motifs which, together with its spacer domain, participate in the protein’s tight interaction with the extracellular matrix.
# Function
ADAMTS7 was identified in a yeast two-hybrid screen using epidermal growth factor (EGF) domain of COMP as the bait. As a metalloproteinase, ADAMTS7 utilizes Zn2+ to catalyze its proteolytic function for COMP degradation.
In vascular smooth muscle cell (VSMC), ADAMTS7 mediates VSMC migration, which plays an essential role during the development of atherosclerosis and restenosis. Adamts7 deficiency in both the Ldlr−/− and Apoe−/− hyperlipidemic mouse models markedly attenuates formation of atherosclerotic lesions; furthermore, wire-injury experiments in the Adamts7−/− mouse show reduced neointima formation. The association of ADAMTS7 with atherosclerosis suggests that inhibition of ADAMTS7 should be atheroprotective in humans.
# Clinical Significance
A negative correlation between the expression levels of specific miRNAs and ADAMTS7 is observed in normal tissues but not in disease tissues, implying an altered miRNA-target interaction in the disease state. Accordingly, expression profiles of these miRNAs and ADAMTS7 may be useful diagnostic tools to differentiate cancer and lichen planus from normal tissues. ADAMTS7 has also been identified as a putative oncogene and reported to be mutated exclusively in Asians, which may have implications for the prevention and treatment of hepatocellular carcinoma. In addition, ADAMTS7 plays a crucial role in the pathogenesis of arthritis. For example, the FGF2/p65/miR-105/Runx2/ADAMTS axis is reportedly involved in osteoarthritis (OA) pathogenesis. Specifically, ADAMTS7 forms a positive feedback loop with tumour necrosis factor (TNF)-α in the pathogenesis of OA.
## Clinical Marker
Genome-wide association studies identified ADAMTS7 as a risk locus for coronary artery disease. Studies have been carried on classification of ADAMTS7 binding site, which may serve as the first step toward developing a new therapeutic target for coronary artery disease. Significant associations for coronary artery calcification with SNPs in ADAMTS7 has also been found in Hispanics. Additionally, a multi-locus genetic risk score study based on a combination of 27 loci, including the ADAMTS7 gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22). | ADAMTS7
A disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS7) is an enzyme that in humans is encoded by the ADAMTS7 gene on chromosome 15.[1] It is ubiquitously expressed in many tissues and cell types.[2] This enzyme catalyzes the degradation of cartilage oligomeric matrix protein (COMP) degradation.[3] ADAMTS7 has been associated with cancer and arthritis in multiple tissue types.[4][5] The ADAMTS7 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.[6]
# Structure
## Gene
The ADAMTS7 gene resides on chromosome 15 at the band 15q24.2 and contains 25 exons.[1]
## Protein
This 1686-amino acid protein belongs to the ADAMTS family and is one of 19 members known in humans. As an ADAMTS protein, ADAMTS7 contains a shared proteinase domain and an ancillary domain. The proteinase domain can be further divided into a signal peptide, a prodomain, a metalloproteinase domain, and a disintegrin-like domain.[7] In particular, the metalloproteinase domain contains a cysteine-switch motif in its binding site for binding the catalytic zinc ion (Zn2+).[8] A pharmacophore model consisting of four hydrogen bond donor sites and three hydrogen bond acceptor sites was proposed for this domain. Unlike the proteinase domain, the ancillary domain varies by ADAMTS protein and includes any number of thrombospondin (TSP) type 1 motifs, one cysteine-rich and spacer domain, and other domains specific to certain ADAMTS proteins.[7] ADAMTS7 in particular possesses 8 TSP type 1 motifs which, together with its spacer domain, participate in the protein’s tight interaction with the extracellular matrix.[8]
# Function
ADAMTS7 was identified in a yeast two-hybrid screen using epidermal growth factor (EGF) domain of COMP as the bait. As a metalloproteinase, ADAMTS7 utilizes Zn2+ to catalyze its proteolytic function for COMP degradation.[3]
In vascular smooth muscle cell (VSMC), ADAMTS7 mediates VSMC migration, which plays an essential role during the development of atherosclerosis and restenosis.[9] Adamts7 deficiency in both the Ldlr−/− and Apoe−/− hyperlipidemic mouse models markedly attenuates formation of atherosclerotic lesions; furthermore, wire-injury experiments in the Adamts7−/− mouse show reduced neointima formation.[10] The association of ADAMTS7 with atherosclerosis suggests that inhibition of ADAMTS7 should be atheroprotective in humans.[10]
# Clinical Significance
A negative correlation between the expression levels of specific miRNAs and ADAMTS7 is observed in normal tissues but not in disease tissues, implying an altered miRNA-target interaction in the disease state. Accordingly, expression profiles of these miRNAs and ADAMTS7 may be useful diagnostic tools to differentiate cancer and lichen planus from normal tissues.[11] ADAMTS7 has also been identified as a putative oncogene and reported to be mutated exclusively in Asians, which may have implications for the prevention and treatment of hepatocellular carcinoma.[4] In addition, ADAMTS7 plays a crucial role in the pathogenesis of arthritis.[5] For example, the FGF2/p65/miR-105/Runx2/ADAMTS axis is reportedly involved in osteoarthritis (OA) pathogenesis.[12] Specifically, ADAMTS7 forms a positive feedback loop with tumour necrosis factor (TNF)-α in the pathogenesis of OA.[13]
## Clinical Marker
Genome-wide association studies identified ADAMTS7 as a risk locus for coronary artery disease. Studies have been carried on classification of ADAMTS7 binding site, which may serve as the first step toward developing a new therapeutic target for coronary artery disease.[7] Significant associations for coronary artery calcification with SNPs in ADAMTS7 has also been found in Hispanics.[14] Additionally, a multi-locus genetic risk score study based on a combination of 27 loci, including the ADAMTS7 gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).[6] | https://www.wikidoc.org/index.php/ADAMTS7 | |
46f0c10a86de9872c3fc73241d9bede003caf340 | wikidoc | ADAMTS8 | ADAMTS8
A disintegrin and metalloproteinase with thrombospondin motifs 8 is an enzyme that in humans is encoded by the ADAMTS8 gene.
# Function
This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The enzyme encoded by this gene contains two C-terminal TS motifs, and disrupts angiogenesis in vivo.
# Clinical significance
A number of disorders have been mapped in the vicinity of this gene, most notably lung neoplasms. | ADAMTS8
A disintegrin and metalloproteinase with thrombospondin motifs 8 is an enzyme that in humans is encoded by the ADAMTS8 gene.[1][2]
# Function
This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The enzyme encoded by this gene contains two C-terminal TS motifs, and disrupts angiogenesis in vivo.[2]
# Clinical significance
A number of disorders have been mapped in the vicinity of this gene, most notably lung neoplasms.[2] | https://www.wikidoc.org/index.php/ADAMTS8 | |
7d6efe181120d46044ad9300b48cd43f7a5a240a | wikidoc | AEMT-CC | AEMT-CC
# Overview
Advanced Emergency Medical Technician - Critical Care (EMT-CC) is an Emergency Medical Services (EMS) certification unique to New York. The curriculum is similar, but beyond that of the national standard EMT-I/99 (Intermediate|EMT-Intermediate - I/99). EMT-CCs are fully classified as Advanced Life Support (ALS) providers within New York and are trained in advanced airway management, IV fluid administration, cardiac monitoring/defibrillation and medication usage/administration in adult and pediatric patients.
# Training
Like all ALS providers, the fundamental prerequisite is current EMT-Basic certification. Most instructors require at least one year of active experience at the EMT-Basic level. On average, students receive approximately 300-400 total hours of instruction. This instruction is broken up into 175-225 classroom/practical laboratory hours, 50-75 clinical hours and 75-100 field internship hours. At the end of the class, students must pass the state's practical skills and written exam to obtain certification. However, an EMT-CC's education never truly ends as many continuing medical education requirements are required to maintain certification.
## In The Classroom
A wide variety of topics are covered in class with specific didactic laboratory time. These topics include:
- Foundations of the EMT-Critical Care Technician
- Overview of Human Systems/Roles and Responsibilities
- Emergency Pharmacology
- Venous Access and Medication Administration
- Airway Management And Ventilation
- Patient Assessment
History Taking
Techniques of Physical Exam
Clinical Decision Making
Communications and Documentation
- History Taking
- Techniques of Physical Exam
- Clinical Decision Making
- Communications and Documentation
- Trauma Emergencies
Trauma Systems and Mechanism of Injury
Hemorrhage and Shock
Burns
Head, Thoracic & Abdominal Trauma
Trauma Practical Laboratory
- Trauma Systems and Mechanism of Injury
- Hemorrhage and Shock
- Burns
- Head, Thoracic & Abdominal Trauma
- Trauma Practical Laboratory
- Medical Emergencies
Respiratory Emergencies
Cardiovascular Emergencies
Diabetic Emergencies
Allergic Reactions
Poison/Overdose
Neurological Emergencies
Non Traumatic Abdominal Emergencies
Environmental Emergencies
Behavioral Emergencies
Gynecological Emergencies
Obstetrical Emergencies
Neonatal Resuscitation
Pediatrics
Geriatrics
- Respiratory Emergencies
- Cardiovascular Emergencies
- Diabetic Emergencies
- Allergic Reactions
- Poison/Overdose
- Neurological Emergencies
- Non Traumatic Abdominal Emergencies
- Environmental Emergencies
- Behavioral Emergencies
- Gynecological Emergencies
- Obstetrical Emergencies
- Neonatal Resuscitation
- Pediatrics
- Geriatrics
## In The Clinical Setting
A significant amount of time is spent observing health care professionals in various clinical settings such as the Emergency Department, Operating Room, Coronary Care Unit, Pediatric Intensive Care Unit, Neonatal Intensive Care Unit, Burn Unit and Medical Intensive Care Unit. The clinical time is designed to expose the student to a large volume and variety of patients in an educational setting so didactic skills and clinical knowledge can be practiced and refined.
## In The Field
EMT-CC students participate in many EMS calls in the field that require ALS skills under an EMT-CC or Paramedic preceptor. Field clinical time represents the phase of instruction where students learn how to apply cognitive knowledge, and the skills developed in the didactic laboratories and hospital clinical time, to the EMS field environment.
# Scope of Practice
EMT-CCs, like all EMS providers, follow a set of protocols for patient care under the guidance of a medical director. These protocols are typically listed in an algorithm format and consist of either routine standing orders or orders that require direct, on-line communication with medical control via radio or telephone. As compared to a Paramedic, an EMT-CC has fewer routine standing orders and requires more contact with medical control.
While the ALS protocols vary slight between the different regions in New York as to which are standing orders versus those which require on-line medical control, all protocols follow current guidelines for Advance Cardiac Life Support (ACLS), Pediatric Advanced Life Support (PALS), Pre-hospital Trauma Life Support (PHTLS), Basic Trauma Life Support (BTLS) and Advanced Trauma Life Support (ATLS). Ultimately, EMT-CC's are capable of initiating venous access, administering medications, performing endotracheal intubation, interpreting ECGs, performing electrical cardiac therapy, performing chest decompression, performing intraosseous access and comply with all state defined Basic Life Support (BLS) protocols.
# Sources
- New York State Department of Health Bureau of EMS Homepage
- New York State AEMT-CC Curriculum on the New York State Deptartment of Health Webpage | AEMT-CC
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Advanced Emergency Medical Technician - Critical Care (EMT-CC) is an Emergency Medical Services (EMS) certification unique to New York. The curriculum is similar, but beyond that of the national standard EMT-I/99 (Intermediate|EMT-Intermediate - I/99). EMT-CCs are fully classified as Advanced Life Support (ALS) providers within New York and are trained in advanced airway management, IV fluid administration, cardiac monitoring/defibrillation and medication usage/administration in adult and pediatric patients.
# Training
Like all ALS providers, the fundamental prerequisite is current EMT-Basic certification. Most instructors require at least one year of active experience at the EMT-Basic level. On average, students receive approximately 300-400 total hours of instruction. This instruction is broken up into 175-225 classroom/practical laboratory hours, 50-75 clinical hours and 75-100 field internship hours. At the end of the class, students must pass the state's practical skills and written exam to obtain certification. However, an EMT-CC's education never truly ends as many continuing medical education requirements are required to maintain certification.
## In The Classroom
A wide variety of topics are covered in class with specific didactic laboratory time. These topics include:
- Foundations of the EMT-Critical Care Technician
- Overview of Human Systems/Roles and Responsibilities
- Emergency Pharmacology
- Venous Access and Medication Administration
- Airway Management And Ventilation
- Patient Assessment
History Taking
Techniques of Physical Exam
Clinical Decision Making
Communications and Documentation
- History Taking
- Techniques of Physical Exam
- Clinical Decision Making
- Communications and Documentation
- Trauma Emergencies
Trauma Systems and Mechanism of Injury
Hemorrhage and Shock
Burns
Head, Thoracic & Abdominal Trauma
Trauma Practical Laboratory
- Trauma Systems and Mechanism of Injury
- Hemorrhage and Shock
- Burns
- Head, Thoracic & Abdominal Trauma
- Trauma Practical Laboratory
- Medical Emergencies
Respiratory Emergencies
Cardiovascular Emergencies
Diabetic Emergencies
Allergic Reactions
Poison/Overdose
Neurological Emergencies
Non Traumatic Abdominal Emergencies
Environmental Emergencies
Behavioral Emergencies
Gynecological Emergencies
Obstetrical Emergencies
Neonatal Resuscitation
Pediatrics
Geriatrics
- Respiratory Emergencies
- Cardiovascular Emergencies
- Diabetic Emergencies
- Allergic Reactions
- Poison/Overdose
- Neurological Emergencies
- Non Traumatic Abdominal Emergencies
- Environmental Emergencies
- Behavioral Emergencies
- Gynecological Emergencies
- Obstetrical Emergencies
- Neonatal Resuscitation
- Pediatrics
- Geriatrics
## In The Clinical Setting
A significant amount of time is spent observing health care professionals in various clinical settings such as the Emergency Department, Operating Room, Coronary Care Unit, Pediatric Intensive Care Unit, Neonatal Intensive Care Unit, Burn Unit and Medical Intensive Care Unit. The clinical time is designed to expose the student to a large volume and variety of patients in an educational setting so didactic skills and clinical knowledge can be practiced and refined.
## In The Field
EMT-CC students participate in many EMS calls in the field that require ALS skills under an EMT-CC or Paramedic preceptor. Field clinical time represents the phase of instruction where students learn how to apply cognitive knowledge, and the skills developed in the didactic laboratories and hospital clinical time, to the EMS field environment.
# Scope of Practice
EMT-CCs, like all EMS providers, follow a set of protocols for patient care under the guidance of a medical director. These protocols are typically listed in an algorithm format and consist of either routine standing orders or orders that require direct, on-line communication with medical control via radio or telephone. As compared to a Paramedic, an EMT-CC has fewer routine standing orders and requires more contact with medical control.
While the ALS protocols vary slight between the different regions in New York as to which are standing orders versus those which require on-line medical control, all protocols follow current guidelines for Advance Cardiac Life Support (ACLS), Pediatric Advanced Life Support (PALS), Pre-hospital Trauma Life Support (PHTLS), Basic Trauma Life Support (BTLS) and Advanced Trauma Life Support (ATLS). Ultimately, EMT-CC's are capable of initiating venous access, administering medications, performing endotracheal intubation, interpreting ECGs, performing electrical cardiac therapy, performing chest decompression, performing intraosseous access and comply with all state defined Basic Life Support (BLS) protocols.
# Sources
- New York State Department of Health Bureau of EMS Homepage
- New York State AEMT-CC Curriculum on the New York State Deptartment of Health Webpage
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/AEMT-CC | |
35cee01ca11289d220c07138098c9c1079d97033 | wikidoc | ALDH1A1 | ALDH1A1
Aldehyde dehydrogenase 1 family, member A1, also known as ALDH1A1 or retinaldehyde dehydrogenase 1 (RALDH1), is an enzyme that in humans is encoded by the ALDH1A1 gene.
# Function
"The protein encoded by this gene belongs to the aldehyde dehydrogenase family. Aldehyde dehydrogenase is the next enzyme after alcohol dehydrogenase in the major pathway of alcohol metabolism. There are two major aldehyde dehydrogenase isozymes in the liver, cytosolic and mitochondrial, which are encoded by distinct genes, and can be distinguished by their electrophoretic mobility, kinetic properties, and subcellular localization. This gene encodes the cytosolic isozyme. Studies in mice show that through its role in retinol metabolism, this gene may also be involved in the regulation of the metabolic responses to high-fat diet."
ALDH1A1 also belongs to the group of corneal crystallins that help maintain the transparency of the cornea.
# Transcriptions
"The promoter region of the gene contains an ATA box and a CCAAT box, which are located 32 and 74 bp upstream, respectively, from the transcription initiation site." | ALDH1A1
Associate Editor(s)-in-Chief: Henry A. Hoff
Aldehyde dehydrogenase 1 family, member A1, also known as ALDH1A1 or retinaldehyde dehydrogenase 1 (RALDH1), is an enzyme that in humans is encoded by the ALDH1A1 gene.[1][2]
# Function
"The protein encoded by this gene belongs to the aldehyde dehydrogenase family. Aldehyde dehydrogenase is the next enzyme after alcohol dehydrogenase in the major pathway of alcohol metabolism. There are two major aldehyde dehydrogenase isozymes in the liver, cytosolic and mitochondrial, which are encoded by distinct genes, and can be distinguished by their electrophoretic mobility, kinetic properties, and subcellular localization. This gene encodes the cytosolic isozyme. Studies in mice show that through its role in retinol metabolism, this gene may also be involved in the regulation of the metabolic responses to high-fat diet."[3]
ALDH1A1 also belongs to the group of corneal crystallins that help maintain the transparency of the cornea.[4]
# Transcriptions
"The promoter region of the gene contains an ATA box and a CCAAT box, which are located 32 and 74 bp upstream, respectively, from the transcription initiation site."[5] | https://www.wikidoc.org/index.php/ALDH1A1 | |
33f5a167b1128da62bbfe235fdb66dcff1891be3 | wikidoc | ALDH1B1 | ALDH1B1
Aldehyde dehydrogenase X, mitochondrial is an enzyme that in humans is encoded by the ALDH1B1 gene.
# Function
This protein belongs to the aldehyde dehydrogenases family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. This gene does not contain introns in the coding sequence. The variation of this locus may affect the development of alcohol-related problems.
# Model organisms
Model organisms have been used in the study of ALDH1B1 function. A conditional knockout mouse line called Aldh1b1tm2a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping - in-depth bone and cartilage phenotyping | ALDH1B1
Aldehyde dehydrogenase X, mitochondrial is an enzyme that in humans is encoded by the ALDH1B1 gene.[1][2]
# Function
This protein belongs to the aldehyde dehydrogenases family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. This gene does not contain introns in the coding sequence. The variation of this locus may affect the development of alcohol-related problems.[2]
# Model organisms
Model organisms have been used in the study of ALDH1B1 function. A conditional knockout mouse line called Aldh1b1tm2a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[3] Male and female animals underwent a standardized phenotypic screen[4] to determine the effects of deletion.[5][6][7][8] Additional screens performed: - In-depth immunological phenotyping[9] - in-depth bone and cartilage phenotyping[10] | https://www.wikidoc.org/index.php/ALDH1B1 | |
f512cd8388a9412b4130f0d34be33818627053bb | wikidoc | ALDH3B1 | ALDH3B1
Aldehyde dehydrogenase 3 family, member B1 also known as ALDH3B1 is an enzyme that in humans is encoded by the ALDH3B1 gene.
# Function
The aldehyde dehydrogenases are a family of isozymes that may play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This particular gene spans about 20 kb of genomic DNA and is composed of 9 coding exons. The gene encodes a single transcript of 2.8 kb that is highly expressed in kidney and lung. The functional significance of this gene and the cellular localization of its product are presently unknown. Two transcript variants encoding different isoforms have been found for this gene.
# Model organisms
Model organisms have been used in the study of ALDH3B1 function. A conditional knockout mouse line called Aldh3b1tm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping - in-depth bone and cartilage phenotyping | ALDH3B1
Aldehyde dehydrogenase 3 family, member B1 also known as ALDH3B1 is an enzyme that in humans is encoded by the ALDH3B1 gene.[1][2]
# Function
The aldehyde dehydrogenases are a family of isozymes that may play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This particular gene spans about 20 kb of genomic DNA and is composed of 9 coding exons. The gene encodes a single transcript of 2.8 kb that is highly expressed in kidney and lung. The functional significance of this gene and the cellular localization of its product are presently unknown. Two transcript variants encoding different isoforms have been found for this gene.[3]
# Model organisms
Model organisms have been used in the study of ALDH3B1 function. A conditional knockout mouse line called Aldh3b1tm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[4] Male and female animals underwent a standardized phenotypic screen[5] to determine the effects of deletion.[6][7][8][9] Additional screens performed: - In-depth immunological phenotyping[10] - in-depth bone and cartilage phenotyping[11] | https://www.wikidoc.org/index.php/ALDH3B1 | |
de07c23118826a9bda0115579baacd4c5ff1d59e | wikidoc | ALDH7A1 | ALDH7A1
Aldehyde dehydrogenase 7 family, member A1, also known as ALDH7A1 or antiquitin, is an enzyme that in humans is encoded by the ALDH7A1 gene. The protein encoded by this gene is a member of subfamily 7 in the aldehyde dehydrogenase gene family. These enzymes are thought to play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This particular member has homology to a previously described protein from the green garden pea, the 26g pea turgor protein. It is also involved in lysine catabolism that is known to occur in the mitochondrial matrix. Recent reports show that this protein is found both in the cytosol and the mitochondria, and the two forms likely arise from the use of alternative translation initiation sites. An additional variant encoding a different isoform has also been found for this gene. Mutations in this gene are associated with pyridoxine-dependent epilepsy. Several related pseudogenes have also been identified.
# Structure
The protein encoded by this gene can localize to the cytosol, mitochondria, or nucleus depending on the inclusion of certain localization sequences. The N-terminal mitochondrial targeting sequence is responsible for mitochondrial localization, while the nuclear localization signal and nuclear export signal are necessary for nuclear localization. Exclusion of the above in the final protein product leads to cytosolic localization. In the protein, two amino acid residues, Glu121 and Arg301, are attributed for the binding and catalyzing one of its substrates, alpha-aminoadipic semialdehyde (α-AASA).
Antiquitin shares 60% homology with the 26g pea turgor protein, also referred to as ALDH7B1, in the green garden pea.
# Function
As a member of subfamily 7 of the aldehyde dehydrogenase gene family, antiquitin performs NAD(P)+-dependent oxidation of aldehydes generated by alcohol metabolism, lipid peroxidation, and other cases of oxidative stress, to their corresponding carboxylic acids . In addition, antiquitin plays a role in protecting cells and tissues from the damaging effects of osmotic stress, presumably through the generation of osmolytes. Antiquitin may also play a protective role for DNA in cell growth, as the protein is found to be up-regulated during the G1–S phase transition, which undergoes the highest degree of oxidative stress in the cell cycle. Furthermore, antiquitin functions as an aldehyde dehydrogenase for α-AASA in the pipecolic acid pathway of lysine catabolism.
## Localization
Antiquitin function and subcellular localization are closely linked, as it functions in detoxification in the cytosol, lysine catabolism in the mitochondrion, and cell cycle progression in the nucleus. In particular, antiquitin localizes to the mitochondria in kidney and liver to contribute to the synthesis of betaine, a chaperone protein that protects against osmotic stress.
# Clinical significance
Mutations in this gene cause pyridoxine-dependent epilepsy, which involves a combination of various seizure types that do not respond to standard anticonvulsants, but are treatable via administration of pyridoxine hydrochloride. These pyridoxine-dependent seizures have been linked to the failure to oxidize α-AASA in patients due to mutated antiquitin. Additionally, antiquitin is implicated in other diseases, including cancer, diabetes, osteoporosis, premature ovarian failure and Huntington's disease, though the exact mechanisms remain unclear.
# Interactions
Antiquitin is known to interact with:
- Cyclin A. | ALDH7A1
Aldehyde dehydrogenase 7 family, member A1, also known as ALDH7A1 or antiquitin, is an enzyme that in humans is encoded by the ALDH7A1 gene.[1] The protein encoded by this gene is a member of subfamily 7 in the aldehyde dehydrogenase gene family. These enzymes are thought to play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This particular member has homology to a previously described protein from the green garden pea, the 26g pea turgor protein. It is also involved in lysine catabolism that is known to occur in the mitochondrial matrix. Recent reports show that this protein is found both in the cytosol and the mitochondria, and the two forms likely arise from the use of alternative translation initiation sites. An additional variant encoding a different isoform has also been found for this gene. Mutations in this gene are associated with pyridoxine-dependent epilepsy. Several related pseudogenes have also been identified.[2]
# Structure
The protein encoded by this gene can localize to the cytosol, mitochondria, or nucleus depending on the inclusion of certain localization sequences. The N-terminal mitochondrial targeting sequence is responsible for mitochondrial localization, while the nuclear localization signal and nuclear export signal are necessary for nuclear localization. Exclusion of the above in the final protein product leads to cytosolic localization. In the protein, two amino acid residues, Glu121 and Arg301, are attributed for the binding and catalyzing one of its substrates, alpha-aminoadipic semialdehyde (α-AASA).[3]
Antiquitin shares 60% homology with the 26g pea turgor protein, also referred to as ALDH7B1, in the green garden pea.[4]
# Function
As a member of subfamily 7 of the aldehyde dehydrogenase gene family, antiquitin performs NAD(P)+-dependent oxidation of aldehydes generated by alcohol metabolism, lipid peroxidation, and other cases of oxidative stress, to their corresponding carboxylic acids .[3][4][5] In addition, antiquitin plays a role in protecting cells and tissues from the damaging effects of osmotic stress, presumably through the generation of osmolytes.[4] Antiquitin may also play a protective role for DNA in cell growth, as the protein is found to be up-regulated during the G1–S phase transition, which undergoes the highest degree of oxidative stress in the cell cycle.[3][4] Furthermore, antiquitin functions as an aldehyde dehydrogenase for α-AASA in the pipecolic acid pathway of lysine catabolism.[3][6]
## Localization
Antiquitin function and subcellular localization are closely linked, as it functions in detoxification in the cytosol, lysine catabolism in the mitochondrion, and cell cycle progression in the nucleus.[3][4] In particular, antiquitin localizes to the mitochondria in kidney and liver to contribute to the synthesis of betaine, a chaperone protein that protects against osmotic stress.[4]
# Clinical significance
Mutations in this gene cause pyridoxine-dependent epilepsy, which involves a combination of various seizure types that do not respond to standard anticonvulsants, but are treatable via administration of pyridoxine hydrochloride.[6][7] These pyridoxine-dependent seizures have been linked to the failure to oxidize α-AASA in patients due to mutated antiquitin. Additionally, antiquitin is implicated in other diseases, including cancer, diabetes, osteoporosis, premature ovarian failure and Huntington's disease, though the exact mechanisms remain unclear.[3][8]
# Interactions
Antiquitin is known to interact with:
- Cyclin A.[9] | https://www.wikidoc.org/index.php/ALDH7A1 | |
237753257c349ce954903ae6212f42a090473393 | wikidoc | ALOX12B | ALOX12B
Arachidonate 12-lipoxygenase, 12R type, also known as ALOX12B, 12R-LOX, and arachiconate lipoygenase 3, is a lipoxygenase-type enzyme composed of 701 amino acids and encoded by the ALOX12B gene. The gene is located on chromosome 17 at position 13.1 where it forms a cluster with two other lipoxygenases, ALOXE3 and ALOX15B. Among the human lipoxygenases, ALOX12B is most closely (54% identity) related in amino acid sequence to ALOXE3
# Activity
ALOX12B oxygenates arachidonic acid by adding molecular oxygen (O2) in the form of a hydroperoxyl (HO2) residue to its 12th carbon thereby forming 12(R)-hydroperoxy-5Z,8Z,10E,14Z-icosatetraenoic acid (also termed 12(R)-HpETE or 12R-HpETE). When formed in cells, 12R-HpETE may be quickly reduced to its hydroxyl analog (OH), 12(R)-hydroxy-5'Z,8Z,10E,14Z-eicosatetraenoic acid (also termed 12(R)-HETE or 12R-HETE), by ubiquitous peroxidase-type enzymes. These sequential metabolic reactions are:
arachidonic acid + O2 \rightleftharpoons 12R-HpETE → 12R-HETE
12R-HETE stimulates animal and human neutrophil chemotaxis and other responses in vitro and is able to elicit inflammatory responses when injected into the skin of an animal model However, the production of 12R-HETE for this or other purposes may not be primary function of ALOX12B.
ALOX12B is also capable of metabolizing free linoleic acid to 9(R)-hydroperoxy-10(E),12(Z)-octadecadienoic acid (9R-HpODE) which is also rapidly converted to its hydroxyl derivative, 9-Hydroxyoctadecadienoic acid (9R-HODE).
Linoleic acid + O2 \rightleftharpoons 9R-HpODE → 9R-HODE
The S stereoisomer of 9R-HODE, 9S-HODE, has a range of biological activities related to oxidative stress and pain perception (see 9-Hydroxyoctadecadienoic acid. It is known or likely that 9R-HODE possesses at least some of these activities. For example, 9R-HODE, similar to 9S-HODE, mediates the perception of acute and chronic pain induced by heat, UV light, and inflammation in the skin of rodents (see 9-Hydroxyoctadecadienoic acid#9-HODEs as mediators of pain perception). However, production of these LA metabolites does not appear to be the primary function of ALOX12B; ALOX12B's primary function appears to be to metabolize linoleic acid that is not free but rather esterified to certain
## Proposed principal activity of ALOX12B
ALOX12B targets Linoleic acid (LA). LA is the most abundant fatty acid in the skin epidermis, being present mainly esterified to the omega-hydroxyl residue of amide-linked omega-hydroxylated very long chain fatty acids (VLCFAs) in a unique class of ceramides termed esterified omega-hydroxyacyl-sphingosine (EOS). EOS is an intermediate component in a proposed multi-step metabolic pathway which delivers VLCFAs to the cornified lipid envelop in the skin's Stratum corneum; the presence of these wax-like, hydrophobic VLCFAs is needed to maintain the skin's integrity and functionality as a water barrier (see Lung microbiome#Role of the epithelial barrier). ALOX12B metabolizes the LA in EOS to its 9-hydroperoxy derivative; ALOXE3 then converts this derivative to three products: a) 9R,10R-trans-epoxide,13R-hydroxy-10E-octadecenoic acid, b) 9-keto-10E,12Z-octadecadienoic acid, and c) 9R,10R-trans-epoxy-13-keto-11E-octadecenoic acid. These ALOX12B-oxidized products signal for the hydrolysis (i.e. removal) of the oxidized products from EOS; this allows the multi-step metabolic pathway to proceed in delivering the VLCFAs to the cornified lipid envelop in the skin's Stratum corneum.
# Tissue distribution
ALOX12B protein has been detected in humans that in the same tissues the express ALOXE3 and ALOX15B viz., upper layers of the human skin and tongue and in tonsils. mRNA for it has been detected in additional tissues such as the lung, testis, adrenal gland, ovary, prostate, and skin with lower abundance levels detected in salivary and thyroid glands, pancreas, brain, and plasma blood leukocytes.
# Clinical significance
## Congenital ichthyosiform erythrodema
Deletions of Alox12b or AloxE2 genes in mice cause a congenital scaly skin disease which is characterized by a greatly reduced skin water barrier function and is similar in other ways to the autosomal recessive nonbullous Congenital ichthyosiform erythroderma (ARCI) disease of humans. Mutations in many of the genes that encode proteins, including ALOX12B and ALOXE3, which conduct the steps that bring and then bind VLCFA to the stratums corneum are associated with ARCI. ARCI refers to nonsyndromic (i.e. not associated with other signs or symptoms) congenital Ichthyosis including Harlequin-type ichthyosis, Lamellar ichthyosis, and Congenital ichthyosiform erythroderma. ARCI has an incidence of about 1/200,000 in European and North American populations; 40 different mutations in ALOX12B and 13 different mutations in ALOXE3 genes account for a total of about 10% of ARCI case; these mutations uniformly cause a total loss of ALOX12B or ALOXE3 function (see mutations).
## Proliferative skin diseases
In psoriasis and other proliferative skin diseases such as the Erythrodermas underlying lung cancer, cutaneous T cell lymphoma, and drug reactions, and in Discoid lupus, Seborrheic dermatitis, Subacute Cutaneous lupus erythematosus, and Pemphigus foliaceus, cutaneous levels of ALOX12B mRNA and 12R-HETE are greatly increased. It is not clear if these increases contribute to the disease by, for example, 12R-HETE induction of inflammation, or are primarily a consequence of skin proliferation.
## Embryogenesis
The expression of Alox12b and Aloxe3 mRNA in mice parallels, and is proposed to be instrumental for, skin development in mice embryogenesis; the human orthologs of these genes, i.e. ALOX12B and ALOXE3, may have a similar role in humans.
## Essential fatty acid deficiency
Severe dietary deficiency of polyunsaturated omega 6 fatty acids leads to the essential fatty acid deficiency syndrome that is characterized by scaly skin and excessive water loss; in humans and animal models the syndrome is fully reversed by dietary omega 6 fatty acids, particularly linoleic acid. It is proposed that this deficiency disease resembles and has a similar basis to Congenital ichthyosiform erythrodema; that is, it is at least in part due to a deficiency of linoleic acid and thereby in the EOS-based delivery of VLCFA to the stratum corneum. | ALOX12B
Arachidonate 12-lipoxygenase, 12R type, also known as ALOX12B, 12R-LOX, and arachiconate lipoygenase 3, is a lipoxygenase-type enzyme composed of 701 amino acids and encoded by the ALOX12B gene.[1][2][3][4] The gene is located on chromosome 17 at position 13.1 where it forms a cluster with two other lipoxygenases, ALOXE3 and ALOX15B.[5] Among the human lipoxygenases, ALOX12B is most closely (54% identity) related in amino acid sequence to ALOXE3[6][7][8]
# Activity
ALOX12B oxygenates arachidonic acid by adding molecular oxygen (O2) in the form of a hydroperoxyl (HO2) residue to its 12th carbon thereby forming 12(R)-hydroperoxy-5Z,8Z,10E,14Z-icosatetraenoic acid (also termed 12(R)-HpETE or 12R-HpETE).[2][3] When formed in cells, 12R-HpETE may be quickly reduced to its hydroxyl analog (OH), 12(R)-hydroxy-5'Z,8Z,10E,14Z-eicosatetraenoic acid (also termed 12(R)-HETE or 12R-HETE), by ubiquitous peroxidase-type enzymes. These sequential metabolic reactions are:
arachidonic acid + O2 <math>\rightleftharpoons</math> 12R-HpETE → 12R-HETE
12R-HETE stimulates animal and human neutrophil chemotaxis and other responses in vitro and is able to elicit inflammatory responses when injected into the skin of an animal model[9][10] However, the production of 12R-HETE for this or other purposes may not be primary function of ALOX12B.
ALOX12B is also capable of metabolizing free linoleic acid to 9(R)-hydroperoxy-10(E),12(Z)-octadecadienoic acid (9R-HpODE) which is also rapidly converted to its hydroxyl derivative, 9-Hydroxyoctadecadienoic acid (9R-HODE).[11]
Linoleic acid + O2 <math>\rightleftharpoons</math> 9R-HpODE → 9R-HODE
The S stereoisomer of 9R-HODE, 9S-HODE, has a range of biological activities related to oxidative stress and pain perception (see 9-Hydroxyoctadecadienoic acid. It is known or likely that 9R-HODE possesses at least some of these activities. For example, 9R-HODE, similar to 9S-HODE, mediates the perception of acute and chronic pain induced by heat, UV light, and inflammation in the skin of rodents (see 9-Hydroxyoctadecadienoic acid#9-HODEs as mediators of pain perception). However, production of these LA metabolites does not appear to be the primary function of ALOX12B; ALOX12B's primary function appears to be to metabolize linoleic acid that is not free but rather esterified to certain[citation needed]
## Proposed principal activity of ALOX12B
ALOX12B targets Linoleic acid (LA). LA is the most abundant fatty acid in the skin epidermis, being present mainly esterified to the omega-hydroxyl residue of amide-linked omega-hydroxylated very long chain fatty acids (VLCFAs) in a unique class of ceramides termed esterified omega-hydroxyacyl-sphingosine (EOS). EOS is an intermediate component in a proposed multi-step metabolic pathway which delivers VLCFAs to the cornified lipid envelop in the skin's Stratum corneum; the presence of these wax-like, hydrophobic VLCFAs is needed to maintain the skin's integrity and functionality as a water barrier (see Lung microbiome#Role of the epithelial barrier).[12] ALOX12B metabolizes the LA in EOS to its 9-hydroperoxy derivative; ALOXE3 then converts this derivative to three products: a) 9R,10R-trans-epoxide,13R-hydroxy-10E-octadecenoic acid, b) 9-keto-10E,12Z-octadecadienoic acid, and c) 9R,10R-trans-epoxy-13-keto-11E-octadecenoic acid.[12][13] These ALOX12B-oxidized products signal for the hydrolysis (i.e. removal) of the oxidized products from EOS; this allows the multi-step metabolic pathway to proceed in delivering the VLCFAs to the cornified lipid envelop in the skin's Stratum corneum.[12][14]
# Tissue distribution
ALOX12B protein has been detected in humans that in the same tissues the express ALOXE3 and ALOX15B viz., upper layers of the human skin and tongue and in tonsils.[5] mRNA for it has been detected in additional tissues such as the lung, testis, adrenal gland, ovary, prostate, and skin with lower abundance levels detected in salivary and thyroid glands, pancreas, brain, and plasma blood leukocytes.[5]
# Clinical significance
## Congenital ichthyosiform erythrodema
Deletions of Alox12b or AloxE2 genes in mice cause a congenital scaly skin disease which is characterized by a greatly reduced skin water barrier function and is similar in other ways to the autosomal recessive nonbullous Congenital ichthyosiform erythroderma (ARCI) disease of humans.[13] Mutations in many of the genes that encode proteins, including ALOX12B and ALOXE3, which conduct the steps that bring and then bind VLCFA to the stratums corneum are associated with ARCI.[15][16] ARCI refers to nonsyndromic (i.e. not associated with other signs or symptoms) congenital Ichthyosis including Harlequin-type ichthyosis, Lamellar ichthyosis, and Congenital ichthyosiform erythroderma.[12] ARCI has an incidence of about 1/200,000 in European and North American populations; 40 different mutations in ALOX12B and 13 different mutations in ALOXE3 genes account for a total of about 10% of ARCI case; these mutations uniformly cause a total loss of ALOX12B or ALOXE3 function (see mutations).[12]
## Proliferative skin diseases
In psoriasis and other proliferative skin diseases such as the Erythrodermas underlying lung cancer, cutaneous T cell lymphoma, and drug reactions, and in Discoid lupus, Seborrheic dermatitis, Subacute Cutaneous lupus erythematosus, and Pemphigus foliaceus, cutaneous levels of ALOX12B mRNA and 12R-HETE are greatly increased.[5][17] It is not clear if these increases contribute to the disease by, for example, 12R-HETE induction of inflammation, or are primarily a consequence of skin proliferation.[12]
## Embryogenesis
The expression of Alox12b and Aloxe3 mRNA in mice parallels, and is proposed to be instrumental for, skin development in mice embryogenesis; the human orthologs of these genes, i.e. ALOX12B and ALOXE3, may have a similar role in humans.[12]
## Essential fatty acid deficiency
Severe dietary deficiency of polyunsaturated omega 6 fatty acids leads to the essential fatty acid deficiency syndrome that is characterized by scaly skin and excessive water loss; in humans and animal models the syndrome is fully reversed by dietary omega 6 fatty acids, particularly linoleic acid.[18] It is proposed that this deficiency disease resembles and has a similar basis to Congenital ichthyosiform erythrodema; that is, it is at least in part due to a deficiency of linoleic acid and thereby in the EOS-based delivery of VLCFA to the stratum corneum.[12] | https://www.wikidoc.org/index.php/ALOX12B | |
52668e53af8aeccfffbaaeb9fdcbcd44fc9ed5e0 | wikidoc | ANDEXXA | ANDEXXA
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Black Box Warning
# Overview
ANDEXXA is a Factor Xa reversal agent that is FDA approved for the {{{indicationType}}} of ANDEXXA, coagulation factor Xa (recombinant), inactivated-zhzo is a recombinant modified human Factor Xa (FXa) protein indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. There is a Black Box Warning for this drug as shown here. Common adverse reactions include urinary tract infections, pneumonia, infusion-related reactions.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Dosing Information
- There are two dosing regimens:
- Low Dose: 400 mg at a target rate of 30 mg/min; Follow-On IV infusion: 4 mg/min for up to 120 minutes
- High Dose: 800 mg at a target rate of 30 mg/min; Follow-On IV infusion: 8 mg/min for up to 120 minutes
- Dosing Information
- For Rivaroxaban ≤ 10 mg, give low dose ANDEXXA if the timing of FXa inhibitor last dose before ANDEXXA initiation is < 8 hours, unknown or ≥ 8 hours
- For Rivaroxaban > 10 mg / Unknown high dose, give high dose ANDEXXA if the timing of FXa inhibitor last dose before ANDEXXA initiation is < 8 hours or unknown and give low dose ANDEXXA if the timing of FXa inhibitor last dose before ANDEXXA initiation is ≥ 8 Hours
- For Apixaban ≤ 5 mg, give low dose ANDEXXA if the timing of FXa inhibitor last dose before ANDEXXA initiation is < 8 hours, unknown or ≥ 8 hours
- For Apixaban > 5 mg / Unknown high dose, give high dose ANDEXXA if the timing of FXa inhibitor last dose before ANDEXXA initiation is < 8 hours or unknown and give low dose ANDEXXA if the timing of FXa inhibitor last dose before ANDEXXA initiation is ≥ 8 Hours
## Off-Label Use and Dosage (Adult)
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- Dosing Information
- The safety and efficacy of ANDEXXA in the pediatric population have not been studied.
## Off-Label Use and Dosage (Pediatric)
# Contraindications
There are no contraindications to the use of ANDEXXA.
# Warnings
- Arterial and venous thromboembolic events, ischemic events, and cardiac events, including sudden death, were observed within 30 days post-ANDEXXA administration in 33 of the 185 patients (18%) evaluable for safety in the ongoing ANNEXA-4 study. The median time to first event was 6 days. Of the 86 patients who were re-anticoagulated prior to a thrombotic event, 11 (12.7%) patients experienced a thromboembolic, ischemic event, cardiac event or death.
- Monitor patients treated with ANDEXXA for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. To reduce thromboembolic risk, resume anticoagulant therapy as soon as medically appropriate following treatment with ANDEXXA.
- The safety of ANDEXXA has not been evaluated in patients who experienced thromboembolic events or disseminated intravascular coagulation within two weeks prior to the life-threatening bleeding event requiring treatment with ANDEXXA. Safety of ANDEXXA also has not been evaluated in patients who received prothrombin complex concentrates, recombinant factor VIIa, or whole blood products within seven days prior to the bleeding event.
- The time course of anti-FXa activity following ANDEXXA administration was consistent among the healthy volunteer studies and the ANNEXA-4 study in bleeding patients.
- Compared to baseline, there was a rapid and substantial decrease in anti-FXa activity corresponding to the ANDEXXA bolus. This decrease was sustained through the end of the ANDEXXA continuous infusion.
- Following the infusion, there was an increase in anti-FXa activity, which peaked 4 hours after infusion in ANNEXA-4 subjects. After this peak, the antiFXa activity decreased at a rate similar to the clearance of the FXa inhibitors.
- Thirty-eight patients who were anticoagulated with apixiban had baseline levels of anti-FXa activity >150 ng/mL. Nineteen of these 38 (50%) patients experienced a > 93% decrease from baseline anti-FXa activity after administration of ANDEXXA. Eleven patients who were anticoagulated with rivaroxaban had baseline anti-FXa activity levels > 300 ng/mL. Five of the 11 patients experienced a >90% decrease from baseline anti-FXa activity after administration of ANDEXXA.
# Adverse Reactions
## Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
- In the pooled safety analysis of clinical trials of ANDEXXA, 223 healthy volunteers received FXa inhibitors followed by treatment with ANDEXXA. The frequency of adverse reactions was similar in the ANDEXXA-treated group (120/223, 54%) and the placebo-treated group (54/94, 57%).
- Infusion-related adverse reactions occurred in 18% (39/223) of the ANDEXXA-treated group, and was the only adverse reaction that occured more frequently than in the placebo group.
- No serious or severe adverse reactions were reported.
- The ANNEXA-4 study is an ongoing multinational, prospective, open-label study using
ANDEXXA in patients presenting with acute major bleeding who have recently received a FXa inhibitor. To date, safety data are available for 185 patients. Approximately half of the patients are male with median age of 78 years.
- Patients had received either apixaban (98/185, 53%) or rivaroxaban (72/185, 40%), as anticoagulation treatment for atrial fibrillation (143/185, 77%) or venous thromboembolism (48/185, 26%). In the majority of patients, ANDEXXA was used to reverse anticoagulant therapy following either an intracranial hemorrhage (106; 57%) or a gastrointestinal bleed (58; 31%), with the remaining 21 patients (11%) experiencing bleeding at other sites. Patients were assessed at a 30-day follow-up visit following infusion of ANDEXXA.
In the ongoing ANNEXA-4 study, 33/185 (17.8%) patients experienced one or more of the following events:
- Deep venous thrombosis (11/33; 33%)
- Ischemic stroke (9/33; 24%)
- Acute myocardial infarction (5/33; 15%)
- Pulmonary embolism (5/33; 15%)
- Cardiogenic shock (3/33;9%)
- Sudden death (2/33; 6%)
- Congestive heart failure (2/33; 6%)
- Acute respiratory failure (2/33; 6%)
- Cardiac arrest (1/33; 3%)
- Cardiac thrombus (1/33; 3%)
- Embolic stroke (1/33; 3%)
- Iliac artery thrombosis (1/33; 3%)
- Non-sustained ventricular tachycardia (1/33; 3%)
- The median time to the first event in these 33 subjects was 6 days Eleven of 33 (33%) patients were on antithrombotic therapy at the time of the event.
- Pneumonia
## Postmarketing Experience
(Description)
# Drug Interactions
- Drug 1
- Drug 2
- Drug 3
- Drug 4
- Drug 5
(Description)
(Description)
(Description)
(Description)
(Description)
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
There are no adequate and well-controlled studies of ANDEXXA in pregnant women to inform patients of associated risks. Animal reproductive and development studies have not been conducted with ANDEXXA. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Pregnancy Category (AUS):
(Description)
### Labor and Delivery
The safety and effectiveness of ANDEXXA during labor and delivery have not been evaluated.
### Nursing Mothers
There is no information regarding the presence of ANDEXXA in human milk, the effects on the breastfed child, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ANDEXXA and any potential adverse effects on the breastfed child from ANDEXXA or from the underlying maternal condition.
### Pediatric Use
The safety and efficacy of ANDEXXA in the pediatric population have not been studied.
### Geriatic Use
Of the 185 subjects in the ANNEXA 4 study of ANDEXXA, 161 were 65 years of age or older and 113 were 75 years of age or older. No overall differences in safety or efficacy were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. The pharmacokinetics of ANDEXXA in older (≥ 65 years, n=10) patients were not different compared to younger (18-45 years, n=10) patients.
### Gender
(Description)
### Race
(Description)
### Renal Impairment
(Description)
### Hepatic Impairment
(Description)
### Females of Reproductive Potential and Males
(Description)
### Immunocompromised Patients
(Description)
### Others
(Description)
# Administration and Monitoring
### Administration
(Oral/Intravenous/etc)
### Monitoring
(Description regarding monitoring, from Warnings section)
(Description regarding monitoring, from Warnings section)
(Description regarding monitoring, from Warnings section)
# IV Compatibility
There is limited information regarding the compatibility of ANDEXXA and IV administrations.
# Overdosage
## Acute Overdose
### Signs and Symptoms
(Description)
### Management
(Description)
## Chronic Overdose
### Signs and Symptoms
(Description)
### Management
(Description)
# Pharmacology
## Mechanism of Action
Coagulation factor Xa (recombinant), inactivated-zhzo exerts its procoagulant effect by binding and sequestering the FXa inhibitors, rivaroxaban and apixaban. Another observed procoagulant effect of the ANDEXXA protein is its ability to bind and inhibit the activity of Tissue Factor Pathway Inhibitor (TFPI). Inhibition of TFPI activity can increase tissue factor-initiated thrombin generation.
## Structure
(Description with picture)
## Pharmacodynamics
The effects of ANDEXXA can be measured using assays for its anti-FXa activity, free fraction of FXa inhibitor and thrombin generation. In addition to its ability to sequester the FXa 10 inhibitors, rivaroxaban and apixaban, ANDEXXA has been shown to inhibit the Tissue Factor Pathway Inhibitor (TFPI) activity. The dose and dosing regimen of ANDEXXA that are required to reverse anti-FXa activity and to restore thrombin generation were determined in dose-ranging studies on healthy volunteers. Dosing of ANDEXXA, as a bolus followed by a 2-hour continuous infusion, resulted in a rapid decrease in anti-FXa activity (within two minutes after the completion of the bolus administration) followed by reduced anti-FXa activity that was maintained throughout the duration of the continuous infusion.The anti-FXa activity returned to the placebo levels approximately 2 hours after completion of a bolus or continuous infusion. Whereas, TFPI activity in plasma was sustained for at least 22 hours following ANDEXXA administration. Elevation of Tissue Factor (TF)-initiated thrombin generation above the baseline range (prior to anticoagulation) occurred within two minutes following a bolus administration of ANDEXXA and was maintained throughout the duration of the continuous infusion. The TF initiated thrombin generation was elevated above placebo for up to 22 hours.The sustained elevation of thrombin generation over the baseline range, and sustained elevation over placebo were not observed in a contact-activated thrombin generation assay (an assay that is not affected by TFTFPI interaction).
## Pharmacokinetics
Distribution
The volume of distribution (Vd) for ANDEXXA is approximately equivalent to the blood
volume of 5 L.
Elimination
Clearance for ANDEXXA is approximately 4.3 L/hr. The elimination half-life ranges from 5 to
7 hours.
Drug-Drug Interaction
The pharmacokinetics of ANDEXXA was not affected by apixaban (5 mg orally BID for 6 days) or rivaroxaban (20 mg orally once daily for 6 days).
## Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
No animal studies were performed to evaluate the effects of ANDEXXA on carcinogenesis, mutagenesis, or impairment of fertility.
# Clinical Studies
The safety and efficacy of ANDEXXA were evaluated in two prospective, randomized, placebocontrolled studies, conducted in healthy volunteers. Both studies examined the percent change in anti-FXa activity, from baseline to nadir, for the low-dose and high-dose regimens of bolus followed by continuous infusion. Nadir is defined as the smallest value measured within 5 minutes after the end of the continuous infusion.
Study 1(NCT02207725) – apixaban reversal
In Study 1, healthy subjects (median age: 57 years; range: 50 to 73 years) received apixaban 5
mg twice daily for 3.5 days to achieve steady-state. At 3 hours after the last apixaban dose (~
Cmax), ANDEXXA or placebo was administered. Eight subjects received placebo and 24
received ANDEXXA, administered as a 400 mg intravenous (IV) bolus followed by a 4 mg per
minute continuous infusion for 120 minutes (total 480 mg).
Study 2 (NCT02220725) – rivaroxaban reversal
In Study 2, healthy subjects (median age: 57 years, range: 50 to 68 years) received rivaroxaban 20 mg once per day for 4 days to achieve steady-state. At 4 hours after the last rivaroxaban dose (~ Cmax), ANDEXXA or placebo was administered. Thirteen subjects received placebo and 26 received ANDEXXA, administered as an 800 mg IV bolus followed by an 8 mg per minute continuous infusion for 120 minutes (total 960 mg).
Reduction in Anti-FXa Activity
The percent change from baseline in anti-FXa activity at its nadir was statistically significant (p < 0.0001) in favor of the ANDEXXA groups compared to placebo in both Studies 1 and 2.
(Description)
# How Supplied
How Supplied
- ANDEXXA is supplied in cartons of 4 single-use vials each containing 100 mg of ANDEXXA as a white to off-white lyophilized cake or powder.
## Storage
There is limited information regarding ANDEXXA Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
Inform patients that reversing FXa inhibitor therapy increases the risk of thromboembolic events. Arterial and venous thromboembolic events, ischemic events, cardiac events, and sudden death were observed within 30 days following ANDEXXA administration.
# Precautions with Alcohol
Alcohol-ANDEXXA interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
# Brand Names
There is limited information regarding ANDEXXA Brand Names in the drug label.
# Look-Alike Drug Names
- (Paired Confused Name 1a) — (Paired Confused Name 1b)
- (Paired Confused Name 2a) — (Paired Confused Name 2b)
- (Paired Confused Name 3a) — (Paired Confused Name 3b)
# Drug Shortage Status
Drug Shortage
# Price | ANDEXXA
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.
# Black Box Warning
# Overview
ANDEXXA is a Factor Xa reversal agent that is FDA approved for the {{{indicationType}}} of ANDEXXA, coagulation factor Xa (recombinant), inactivated-zhzo is a recombinant modified human Factor Xa (FXa) protein indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. There is a Black Box Warning for this drug as shown here. Common adverse reactions include urinary tract infections, pneumonia, infusion-related reactions.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Dosing Information
- There are two dosing regimens:
- Low Dose: 400 mg at a target rate of 30 mg/min; Follow-On IV infusion: 4 mg/min for up to 120 minutes
- High Dose: 800 mg at a target rate of 30 mg/min; Follow-On IV infusion: 8 mg/min for up to 120 minutes
- Dosing Information
- For Rivaroxaban ≤ 10 mg, give low dose ANDEXXA if the timing of FXa inhibitor last dose before ANDEXXA initiation is < 8 hours, unknown or ≥ 8 hours
- For Rivaroxaban > 10 mg / Unknown high dose, give high dose ANDEXXA if the timing of FXa inhibitor last dose before ANDEXXA initiation is < 8 hours or unknown and give low dose ANDEXXA if the timing of FXa inhibitor last dose before ANDEXXA initiation is ≥ 8 Hours
- For Apixaban ≤ 5 mg, give low dose ANDEXXA if the timing of FXa inhibitor last dose before ANDEXXA initiation is < 8 hours, unknown or ≥ 8 hours
- For Apixaban > 5 mg / Unknown high dose, give high dose ANDEXXA if the timing of FXa inhibitor last dose before ANDEXXA initiation is < 8 hours or unknown and give low dose ANDEXXA if the timing of FXa inhibitor last dose before ANDEXXA initiation is ≥ 8 Hours
## Off-Label Use and Dosage (Adult)
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- Dosing Information
- The safety and efficacy of ANDEXXA in the pediatric population have not been studied.
## Off-Label Use and Dosage (Pediatric)
# Contraindications
There are no contraindications to the use of ANDEXXA.
# Warnings
- Arterial and venous thromboembolic events, ischemic events, and cardiac events, including sudden death, were observed within 30 days post-ANDEXXA administration in 33 of the 185 patients (18%) evaluable for safety in the ongoing ANNEXA-4 study. The median time to first event was 6 days. Of the 86 patients who were re-anticoagulated prior to a thrombotic event, 11 (12.7%) patients experienced a thromboembolic, ischemic event, cardiac event or death.
- Monitor patients treated with ANDEXXA for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. To reduce thromboembolic risk, resume anticoagulant therapy as soon as medically appropriate following treatment with ANDEXXA.
- The safety of ANDEXXA has not been evaluated in patients who experienced thromboembolic events or disseminated intravascular coagulation within two weeks prior to the life-threatening bleeding event requiring treatment with ANDEXXA. Safety of ANDEXXA also has not been evaluated in patients who received prothrombin complex concentrates, recombinant factor VIIa, or whole blood products within seven days prior to the bleeding event.
- The time course of anti-FXa activity following ANDEXXA administration was consistent among the healthy volunteer studies and the ANNEXA-4 study in bleeding patients.
- Compared to baseline, there was a rapid and substantial decrease in anti-FXa activity corresponding to the ANDEXXA bolus. This decrease was sustained through the end of the ANDEXXA continuous infusion.
- Following the infusion, there was an increase in anti-FXa activity, which peaked 4 hours after infusion in ANNEXA-4 subjects. After this peak, the antiFXa activity decreased at a rate similar to the clearance of the FXa inhibitors.
- Thirty-eight patients who were anticoagulated with apixiban had baseline levels of anti-FXa activity >150 ng/mL. Nineteen of these 38 (50%) patients experienced a > 93% decrease from baseline anti-FXa activity after administration of ANDEXXA. Eleven patients who were anticoagulated with rivaroxaban had baseline anti-FXa activity levels > 300 ng/mL. Five of the 11 patients experienced a >90% decrease from baseline anti-FXa activity after administration of ANDEXXA.
# Adverse Reactions
## Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
- In the pooled safety analysis of clinical trials of ANDEXXA, 223 healthy volunteers received FXa inhibitors followed by treatment with ANDEXXA. The frequency of adverse reactions was similar in the ANDEXXA-treated group (120/223, 54%) and the placebo-treated group (54/94, 57%).
- Infusion-related adverse reactions occurred in 18% (39/223) of the ANDEXXA-treated group, and was the only adverse reaction that occured more frequently than in the placebo group.
- No serious or severe adverse reactions were reported.
- The ANNEXA-4 study is an ongoing multinational, prospective, open-label study using
ANDEXXA in patients presenting with acute major bleeding who have recently received a FXa inhibitor. To date, safety data are available for 185 patients. Approximately half of the patients are male with median age of 78 years.
- Patients had received either apixaban (98/185, 53%) or rivaroxaban (72/185, 40%), as anticoagulation treatment for atrial fibrillation (143/185, 77%) or venous thromboembolism (48/185, 26%). In the majority of patients, ANDEXXA was used to reverse anticoagulant therapy following either an intracranial hemorrhage (106; 57%) or a gastrointestinal bleed (58; 31%), with the remaining 21 patients (11%) experiencing bleeding at other sites. Patients were assessed at a 30-day follow-up visit following infusion of ANDEXXA.
In the ongoing ANNEXA-4 study, 33/185 (17.8%) patients experienced one or more of the following events:
- Deep venous thrombosis (11/33; 33%)
- Ischemic stroke (9/33; 24%)
- Acute myocardial infarction (5/33; 15%)
- Pulmonary embolism (5/33; 15%)
- Cardiogenic shock (3/33;9%)
- Sudden death (2/33; 6%)
- Congestive heart failure (2/33; 6%)
- Acute respiratory failure (2/33; 6%)
- Cardiac arrest (1/33; 3%)
- Cardiac thrombus (1/33; 3%)
- Embolic stroke (1/33; 3%)
- Iliac artery thrombosis (1/33; 3%)
- Non-sustained ventricular tachycardia (1/33; 3%)
- The median time to the first event in these 33 subjects was 6 days Eleven of 33 (33%) patients were on antithrombotic therapy at the time of the event.
- Pneumonia
## Postmarketing Experience
(Description)
# Drug Interactions
- Drug 1
- Drug 2
- Drug 3
- Drug 4
- Drug 5
(Description)
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(Description)
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
There are no adequate and well-controlled studies of ANDEXXA in pregnant women to inform patients of associated risks. Animal reproductive and development studies have not been conducted with ANDEXXA. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Pregnancy Category (AUS):
(Description)
### Labor and Delivery
The safety and effectiveness of ANDEXXA during labor and delivery have not been evaluated.
### Nursing Mothers
There is no information regarding the presence of ANDEXXA in human milk, the effects on the breastfed child, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ANDEXXA and any potential adverse effects on the breastfed child from ANDEXXA or from the underlying maternal condition.
### Pediatric Use
The safety and efficacy of ANDEXXA in the pediatric population have not been studied.
### Geriatic Use
Of the 185 subjects in the ANNEXA 4 study of ANDEXXA, 161 were 65 years of age or older and 113 were 75 years of age or older. No overall differences in safety or efficacy were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. The pharmacokinetics of ANDEXXA in older (≥ 65 years, n=10) patients were not different compared to younger (18-45 years, n=10) patients.
### Gender
(Description)
### Race
(Description)
### Renal Impairment
(Description)
### Hepatic Impairment
(Description)
### Females of Reproductive Potential and Males
(Description)
### Immunocompromised Patients
(Description)
### Others
(Description)
# Administration and Monitoring
### Administration
(Oral/Intravenous/etc)
### Monitoring
(Description regarding monitoring, from Warnings section)
(Description regarding monitoring, from Warnings section)
(Description regarding monitoring, from Warnings section)
# IV Compatibility
There is limited information regarding the compatibility of ANDEXXA and IV administrations.
# Overdosage
## Acute Overdose
### Signs and Symptoms
(Description)
### Management
(Description)
## Chronic Overdose
### Signs and Symptoms
(Description)
### Management
(Description)
# Pharmacology
## Mechanism of Action
Coagulation factor Xa (recombinant), inactivated-zhzo exerts its procoagulant effect by binding and sequestering the FXa inhibitors, rivaroxaban and apixaban. Another observed procoagulant effect of the ANDEXXA protein is its ability to bind and inhibit the activity of Tissue Factor Pathway Inhibitor (TFPI). Inhibition of TFPI activity can increase tissue factor-initiated thrombin generation.
## Structure
(Description with picture)
## Pharmacodynamics
The effects of ANDEXXA can be measured using assays for its anti-FXa activity, free fraction of FXa inhibitor and thrombin generation. In addition to its ability to sequester the FXa 10 inhibitors, rivaroxaban and apixaban, ANDEXXA has been shown to inhibit the Tissue Factor Pathway Inhibitor (TFPI) activity. The dose and dosing regimen of ANDEXXA that are required to reverse anti-FXa activity and to restore thrombin generation were determined in dose-ranging studies on healthy volunteers. Dosing of ANDEXXA, as a bolus followed by a 2-hour continuous infusion, resulted in a rapid decrease in anti-FXa activity (within two minutes after the completion of the bolus administration) followed by reduced anti-FXa activity that was maintained throughout the duration of the continuous infusion.The anti-FXa activity returned to the placebo levels approximately 2 hours after completion of a bolus or continuous infusion. Whereas, TFPI activity in plasma was sustained for at least 22 hours following ANDEXXA administration. Elevation of Tissue Factor (TF)-initiated thrombin generation above the baseline range (prior to anticoagulation) occurred within two minutes following a bolus administration of ANDEXXA and was maintained throughout the duration of the continuous infusion. The TF initiated thrombin generation was elevated above placebo for up to 22 hours.The sustained elevation of thrombin generation over the baseline range, and sustained elevation over placebo were not observed in a contact-activated thrombin generation assay (an assay that is not affected by TFTFPI interaction).
## Pharmacokinetics
Distribution
The volume of distribution (Vd) for ANDEXXA is approximately equivalent to the blood
volume of 5 L.
Elimination
Clearance for ANDEXXA is approximately 4.3 L/hr. The elimination half-life ranges from 5 to
7 hours.
Drug-Drug Interaction
The pharmacokinetics of ANDEXXA was not affected by apixaban (5 mg orally BID for 6 days) or rivaroxaban (20 mg orally once daily for 6 days).
## Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
No animal studies were performed to evaluate the effects of ANDEXXA on carcinogenesis, mutagenesis, or impairment of fertility.
# Clinical Studies
The safety and efficacy of ANDEXXA were evaluated in two prospective, randomized, placebocontrolled studies, conducted in healthy volunteers. Both studies examined the percent change in anti-FXa activity, from baseline to nadir, for the low-dose and high-dose regimens of bolus followed by continuous infusion. Nadir is defined as the smallest value measured within 5 minutes after the end of the continuous infusion.
Study 1(NCT02207725) – apixaban reversal
In Study 1, healthy subjects (median age: 57 years; range: 50 to 73 years) received apixaban 5
mg twice daily for 3.5 days to achieve steady-state. At 3 hours after the last apixaban dose (~
Cmax), ANDEXXA or placebo was administered. Eight subjects received placebo and 24
received ANDEXXA, administered as a 400 mg intravenous (IV) bolus followed by a 4 mg per
minute continuous infusion for 120 minutes (total 480 mg).
Study 2 (NCT02220725) – rivaroxaban reversal
In Study 2, healthy subjects (median age: 57 years, range: 50 to 68 years) received rivaroxaban 20 mg once per day for 4 days to achieve steady-state. At 4 hours after the last rivaroxaban dose (~ Cmax), ANDEXXA or placebo was administered. Thirteen subjects received placebo and 26 received ANDEXXA, administered as an 800 mg IV bolus followed by an 8 mg per minute continuous infusion for 120 minutes (total 960 mg).
Reduction in Anti-FXa Activity
The percent change from baseline in anti-FXa activity at its nadir was statistically significant (p < 0.0001) in favor of the ANDEXXA groups compared to placebo in both Studies 1 and 2.
(Description)
# How Supplied
How Supplied
- ANDEXXA is supplied in cartons of 4 single-use vials each containing 100 mg of ANDEXXA as a white to off-white lyophilized cake or powder.
## Storage
There is limited information regarding ANDEXXA Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
Inform patients that reversing FXa inhibitor therapy increases the risk of thromboembolic events. Arterial and venous thromboembolic events, ischemic events, cardiac events, and sudden death were observed within 30 days following ANDEXXA administration.
# Precautions with Alcohol
Alcohol-ANDEXXA interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
# Brand Names
There is limited information regarding ANDEXXA Brand Names in the drug label.
# Look-Alike Drug Names
- (Paired Confused Name 1a) — (Paired Confused Name 1b)
- (Paired Confused Name 2a) — (Paired Confused Name 2b)
- (Paired Confused Name 3a) — (Paired Confused Name 3b)
# Drug Shortage Status
Drug Shortage
# Price | https://www.wikidoc.org/index.php/ANDEXXA | |
e15baaaf82c8df6cd5d383b33f65b73cead49b27 | wikidoc | ANGPTL3 | ANGPTL3
Angiopoietin-like 3, also known as ANGPTL3, is a protein that in humans is encoded by the ANGPTL3 gene.
# Function
The protein encoded by this gene is a member of the angiopoietin-like family of secreted factors. It is expressed predominantly in the liver, and has the characteristic structure of angiopoietins, consisting of a signal peptide, N-terminal coiled-coil domain, and the C-terminal fibrinogen (FBN)-like domain. The FBN-like domain in angiopoietin-like 3 protein was shown to bind alpha-5/beta-3 integrins, and this binding induced endothelial cell adhesion and migration. This protein may also play a role in the regulation of angiogenesis.
Angptl3 also acts as dual inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL), thereby increasing plasma triglyceride, LDL cholesterol and HDL cholesterol in mice and humans.
ANGPTL3 inhibits endothelial lipase hydrolysis of HDL-phospholipid (PL), thereby increasing HDL-PL levels. Circulating PL-rich HDL particles have high cholesterol efflux abilities.
Angptl3 plays a major role in promoting uptake of circulating triglycerides into white adipose tissue in the fed state, likely through activation by Angptl8, a feeding-induced hepatokine, to inhibit postprandial LPL activity in cardiac and skeletal muscles, as suggested by the ANGPTL3-4-8 model.
# Clinical significance
In human, ANGPTL3 is a determinant factor of HDL level and positively correlates with plasma HDL cholesterol.
In humans with genetic loss-of-function variants in one copy of ANGPTL3, the serum LDL-C levels are reduced. In those with loss-of-function variants in both copies of ANGPTL3, low LDL-C, low HDL-C, and low triglycerides are seen ("familial combined hypolipidemia"). | ANGPTL3
Angiopoietin-like 3, also known as ANGPTL3, is a protein that in humans is encoded by the ANGPTL3 gene.[1][2]
# Function
The protein encoded by this gene is a member of the angiopoietin-like family of secreted factors. It is expressed predominantly in the liver, and has the characteristic structure of angiopoietins, consisting of a signal peptide, N-terminal coiled-coil domain, and the C-terminal fibrinogen (FBN)-like domain. The FBN-like domain in angiopoietin-like 3 protein was shown to bind alpha-5/beta-3 integrins, and this binding induced endothelial cell adhesion and migration. This protein may also play a role in the regulation of angiogenesis.[1]
Angptl3 also acts as dual inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL),[3] thereby increasing plasma triglyceride, LDL cholesterol and HDL cholesterol in mice and humans.[3]
ANGPTL3 inhibits endothelial lipase hydrolysis of HDL-phospholipid (PL), thereby increasing HDL-PL levels.[citation needed] Circulating PL-rich HDL particles have high cholesterol efflux abilities.[citation needed]
Angptl3 plays a major role in promoting uptake of circulating triglycerides into white adipose tissue in the fed state,[4] likely through activation by Angptl8, a feeding-induced hepatokine,[5][6] to inhibit postprandial LPL activity in cardiac and skeletal muscles,[7] as suggested by the ANGPTL3-4-8 model.[8]
# Clinical significance
In human, ANGPTL3 is a determinant factor of HDL level and positively correlates with plasma HDL cholesterol.
In humans with genetic loss-of-function variants in one copy of ANGPTL3, the serum LDL-C levels are reduced. In those with loss-of-function variants in both copies of ANGPTL3, low LDL-C, low HDL-C, and low triglycerides are seen ("familial combined hypolipidemia").[9] | https://www.wikidoc.org/index.php/ANGPTL3 | |
eb833c338325b5fdf9f3663815b6cffb353f7510 | wikidoc | ANGPTL4 | ANGPTL4
Angiopoietin-like 4 is a protein that in human is encoded by the ANGPTL4 gene. Alternatively spliced transcript variants encoding different isoforms have been described. This gene was previously referred to as ANGPTL2, HFARP, PGAR, or FIAF but has been renamed ANGPTL4.
# Structure
This gene is a member of the angiopoietin-like gene family and encodes a glycosylated, secreted protein with a coiled-coil N-terminal domain and a fibrinogen-like C-terminal domain.
# Expression
In mice, highest mRNA expression levels of ANGPTL4 are found in white and brown adipose tissue, followed by liver, kidney, muscle and intestine. Human ANGPTL4 is most highly expressed in liver.
# Function
This gene is induced under hypoxic (low oxygen) condition in various cell types and is the target of Peroxisome proliferator-activated receptors. The encoded protein is a serum hormone directly involved in regulating lipid metabolism. The native full length ANGPTL4 can form higher order structures via intermolecular disulfide bonds. The N-terminal region of ANGPTL4 (nANGPTL4) is responsible for its assembly. The full length ANGPTL4 undergoes proteolytic cleavage at the linker region, releasing nANGPTL4 and the monomeric C-terminal portion of ANGPTL4 (cANGPTL4). The nANGPTL4 and cANGPTL4 have different biological functions. Monoclonal antibodies targeting the nANGPTL4 and cANGPTL4 have been developed to distinguish their functions.
# Clinical significance
ANGPTL4 plays an important role in numerous cancers and is implicated in the metastatic process by modulating vascular permeability, cancer cell motility and invasiveness. ANGPTL4 contributes to tumor growth and protects cells from anoikis, a form of programmed cell death induced when contact-dependent cells detach from the surrounding tissue matrix. ANGPTL4 secreted from tumors can bind to integrins, activating downstream signaling and leading to the production of superoxide to promote tumorigenesis. ANGPTL4 disrupts endothelial cell junctions by directly interacting with integrin, VE-cadherin and claudin-5 in a sequential manner to facilitate metastasis. ANGPTL4 functions as a matricellular protein to facilitate skin wound healing. ANGPTL4-deficient mice exhibit delayed wound reepithelialization with impaired keratinocyte migration, angiogenesis and altered inflammatory response. ANGPTL4 induces nitric oxide production through an integrin/JAK/STAT3-mediated upregulation of iNOS expression in wound epithelia, and enhances angiogenesis to accelerate wound healing in diabetic mice. Cyclic stretching of human tendon fibroblasts stimulated the expression and release of ANGPTL4 protein via TGF-β and HIF-1α signalling, and the released ANGPTL4 was pro-angiogenic. ANGPTL4 is also a potent angiogenic factor whose expression is up-regulated in hypoxic retinal Müller cells in vitro and the ischemic retina in vivo. The expression of ANGPTL4 was increased in the aqueous and vitreous of proliferative diabetic retinopathy patients and localized to areas of retinal neovascularization.
ANGPTL4 has been established as a potent inhibitor of serum triglyceride (TG) clearance, causing elevation of serum TG levels via inhibition of the enzyme lipoprotein lipase (LPL). Biochemical studies indicate that ANGPTL4 disables LPL partly by dissociating the catalytically active LPL dimer into inactive LPL monomers. However, evidence also suggests that ANGPTL4 functions as a conventional, non-competitive inhibitor that binds to LPL to prevent the hydrolysis of substrate as part of reversible mechanism. As a consequence, ANGPTL4 knockout mice have reduced serum triglyceride levels, whereas the opposite is true for mice over-expressing ANGPTL4. ANGPTL4 suppresses foam cell formation to reduce atherosclerosis development. The reduction in LPL activity in adipose tissue during fasting is likely caused by increased local production of ANGPTL4. In other tissues such as heart, production of ANGPTL4 is stimulated by fatty acids and may serve to protect cells against excess fat uptake. ANGPTL4 is more highly induced in nonexercising muscle than in exercising human muscle during acute exercise. ANGPTL4 in nonexercising muscle presumably leads to reduced local uptake of plasma triglyceride-derived fatty acids and their sparing for use by exercising muscle. The induction of ANGPTL4 in exercising muscle likely is counteracted via AMP-activated protein kinase (AMPK)-mediated down-regulation, promoting the use of plasma triglycerides as fuel for active muscles.
High-throughput RNA sequencing of lung tissue samples from the 1918 and 2009 influenza pandemic revealed that ANGPTL4 was one of the most significantly upregulated gene. Murine influenza infection of the lungs stimulated the expression of ANGPTL4 via a STAT3-mediated mechanism. ANGPTL4 enhanced pulmonary tissue leakiness and exacerbated inflammation-induced lung damage. Influenza-infected ANGPTL4-knockout mice displayed diminished lung damage and recovered faster from the infection compared to wild-type mice. The treatment of infected mice with neutralizing anti-ANGPTL4 antibodies significantly accelerated pulmonary recovery and improved lung tissue integrity. | ANGPTL4
Angiopoietin-like 4 is a protein that in human is encoded by the ANGPTL4 gene.[1][2][3] Alternatively spliced transcript variants encoding different isoforms have been described. This gene was previously referred to as ANGPTL2, HFARP, PGAR, or FIAF but has been renamed ANGPTL4.
# Structure
This gene is a member of the angiopoietin-like gene family and encodes a glycosylated, secreted protein with a coiled-coil N-terminal domain and a fibrinogen-like C-terminal domain.[4]
# Expression
In mice, highest mRNA expression levels of ANGPTL4 are found in white and brown adipose tissue, followed by liver, kidney, muscle and intestine. Human ANGPTL4 is most highly expressed in liver.
# Function
This gene is induced under hypoxic (low oxygen) condition in various cell types and is the target of Peroxisome proliferator-activated receptors. The encoded protein is a serum hormone directly involved in regulating lipid metabolism. The native full length ANGPTL4 can form higher order structures via intermolecular disulfide bonds. The N-terminal region of ANGPTL4 (nANGPTL4) is responsible for its assembly. The full length ANGPTL4 undergoes proteolytic cleavage at the linker region, releasing nANGPTL4 and the monomeric C-terminal portion of ANGPTL4 (cANGPTL4). The nANGPTL4 and cANGPTL4 have different biological functions.[4] Monoclonal antibodies targeting the nANGPTL4[5] and cANGPTL4[6] have been developed to distinguish their functions.
# Clinical significance
ANGPTL4 plays an important role in numerous cancers and is implicated in the metastatic process by modulating vascular permeability, cancer cell motility and invasiveness.[7][8][9] ANGPTL4 contributes to tumor growth and protects cells from anoikis, a form of programmed cell death induced when contact-dependent cells detach from the surrounding tissue matrix.[6] ANGPTL4 secreted from tumors can bind to integrins, activating downstream signaling and leading to the production of superoxide to promote tumorigenesis.[10] ANGPTL4 disrupts endothelial cell junctions by directly interacting with integrin, VE-cadherin and claudin-5 in a sequential manner to facilitate metastasis.[11] ANGPTL4 functions as a matricellular protein[12] to facilitate skin wound healing. ANGPTL4-deficient mice exhibit delayed wound reepithelialization with impaired keratinocyte migration, angiogenesis and altered inflammatory response.[13][14] ANGPTL4 induces nitric oxide production through an integrin/JAK/STAT3-mediated upregulation of iNOS expression in wound epithelia, and enhances angiogenesis to accelerate wound healing in diabetic mice.[15] Cyclic stretching of human tendon fibroblasts stimulated the expression and release of ANGPTL4 protein via TGF-β and HIF-1α signalling, and the released ANGPTL4 was pro-angiogenic.[16] ANGPTL4 is also a potent angiogenic factor whose expression is up-regulated in hypoxic retinal Müller cells in vitro and the ischemic retina in vivo. The expression of ANGPTL4 was increased in the aqueous and vitreous of proliferative diabetic retinopathy patients and localized to areas of retinal neovascularization.[17]
ANGPTL4 has been established as a potent inhibitor of serum triglyceride (TG) clearance, causing elevation of serum TG levels via inhibition of the enzyme lipoprotein lipase (LPL). Biochemical studies indicate that ANGPTL4 disables LPL partly by dissociating the catalytically active LPL dimer into inactive LPL monomers.[18] However, evidence also suggests that ANGPTL4 functions as a conventional, non-competitive inhibitor that binds to LPL to prevent the hydrolysis of substrate as part of reversible mechanism.[19] As a consequence, ANGPTL4 knockout mice have reduced serum triglyceride levels, whereas the opposite is true for mice over-expressing ANGPTL4. ANGPTL4 suppresses foam cell formation to reduce atherosclerosis development.[20] The reduction in LPL activity in adipose tissue during fasting is likely caused by increased local production of ANGPTL4. In other tissues such as heart, production of ANGPTL4 is stimulated by fatty acids and may serve to protect cells against excess fat uptake.[21] ANGPTL4 is more highly induced in nonexercising muscle than in exercising human muscle during acute exercise. ANGPTL4 in nonexercising muscle presumably leads to reduced local uptake of plasma triglyceride-derived fatty acids and their sparing for use by exercising muscle. The induction of ANGPTL4 in exercising muscle likely is counteracted via AMP-activated protein kinase (AMPK)-mediated down-regulation, promoting the use of plasma triglycerides as fuel for active muscles.[22]
High-throughput RNA sequencing of lung tissue samples from the 1918 and 2009 influenza pandemic revealed that ANGPTL4 was one of the most significantly upregulated gene.[23] Murine influenza infection of the lungs stimulated the expression of ANGPTL4 via a STAT3-mediated mechanism. ANGPTL4 enhanced pulmonary tissue leakiness and exacerbated inflammation-induced lung damage. Influenza-infected ANGPTL4-knockout mice displayed diminished lung damage and recovered faster from the infection compared to wild-type mice. The treatment of infected mice with neutralizing anti-ANGPTL4 antibodies significantly accelerated pulmonary recovery and improved lung tissue integrity.[24] | https://www.wikidoc.org/index.php/ANGPTL4 | |
0f1076177ed94c3f668ddb041fb8aa1cb460773b | wikidoc | ANGPTL8 | ANGPTL8
ANGPTL8 (also known as lipasin, originally Betatrophin) is a protein that in humans is encoded by the C19orf80 gene.
# Gene
The gene for betatrophin lies on mouse chromosome 9 (gene symbol: Gm6484) and on human chromosome 19 (gene symbol: C19orf80).
# Discovery
The link between betatrophin and mouse islet cell proliferation was made by Douglas Melton and Peng Yi from Harvard in 2013. However, this link has been quickly proven false by other researchers. In fact, in December 2016 the original paper by Melton and Yi was retracted, putting the link between betatrophin and islets cells to rest. Given the status of betatrophin and taking into account that betatrophin is a member of the angiopoietin-like gene family and shares extensive homology with Angptl4 and Angptl3, the name betatrophin should be abandoned in favor of Angptl8. Other names for betatrophin include TD26, RIFL, and Lipasin.
# Function
Betatrophin is a putative peptide hormone found in mice that was proposed to increase the rate at which beta-cells undergo cell division. Injection of mice with betatrophin cDNA lowered blood sugar (i.e. hypoglycemia), presumably due to action at the pancreas. However, treatment of human islets with betatrophin is unable to increase beta-cell division. Furthermore, studies in betatrophin/Angptl8 knock-out mice do not support a role of betatrophin in controlling beta cell growth, yet point to a clear role in regulating plasma triglyceride levels. Based on these studies, it is fairly safe to say that the notion that betatrophin promotes beta cell expansion is dead, which was made official by the retraction of the original paper. Deletion of betatrophin/Angptl8 does not seem to impact glucose and insulin tolerance in mice.
The encoded 22 kDa protein contains an N-terminal secretion signal and two coiled-coil domains and is a member of the angiopoietin-like (ANGPTL) protein family. However, in contrast to other ANGPTL proteins, betatrophin lacks the C-terminal fibrinogen-like domain, and therefore it is an atypical member of the ANGPTL family. It shares with Angptl4 and Angptl3 the ability to inhibit the enzyme Lipoprotein lipase (LPL), and its hepatic overexpression causes elevation of circulating Triglyceride levels in mice. In mice betatrophin is secreted by the liver.
Despite having elevated post-heparin plasma LPL activity, mice lacking betatrophin/Angptl8 exhibit markedly decreased uptake of Very low-density lipoprotein-derived fatty acids into white adipose tissue (WAT). The defect in fatty acids uptake by WAT in Angptl8-null mice is likely due to the enhanced fatty acids uptake by the heart and skeletal muscle, because of the elevated LPL activity in these two tissues, as suggested by the ANGPTL3-4-8 model.
# Structure
Three dimensional structure of none of the members of Angiopoietin like proteins (ANGPTLs) is available up till now. However, the structure of ANGPTL8 was predicted by homology modeling and is also reported in literature. It consists of alpha helices and its sequence show high similarity with the coiled-coil domains of ANGPTL3 and ANGPTL4.
# Pathway
The ANGPTL8 regulatory pathway has been constructed recently by integrating the information of its know transcription factors which is available at WikiPathways data repository with the pathway id WP3915.
# Clinical significance
It was hoped that betatrophin or its homolog in humans may provide an effective treatment for type 2 diabetes and perhaps even type I diabetes. Unfortunately, since new data have greatly called into question the ability of betatrophin to increase beta-cell replication, its potential use as a therapy for type 2 diabetes is limited. Inhibition of Angptl8 represents a possible therapeutic strategy for hypertriglyceridemia. | ANGPTL8
ANGPTL8 (also known as lipasin, originally Betatrophin) is a protein that in humans is encoded by the C19orf80 gene.
# Gene
The gene for betatrophin lies on mouse chromosome 9 (gene symbol: Gm6484) and on human chromosome 19 (gene symbol: C19orf80).
# Discovery
The link between betatrophin and mouse islet cell proliferation was made by Douglas Melton and Peng Yi from Harvard in 2013.[1] However, this link has been quickly proven false by other researchers.[2] In fact, in December 2016 the original paper by Melton and Yi was retracted, putting the link between betatrophin and islets cells to rest. Given the status of betatrophin and taking into account that betatrophin is a member of the angiopoietin-like gene family and shares extensive homology with Angptl4 and Angptl3, the name betatrophin should be abandoned in favor of Angptl8. Other names for betatrophin include TD26, RIFL, and Lipasin.[3]
# Function
Betatrophin is a putative peptide hormone found in mice that was proposed to increase the rate at which beta-cells undergo cell division. Injection of mice with betatrophin cDNA lowered blood sugar (i.e. hypoglycemia), presumably due to action at the pancreas. However, treatment of human islets with betatrophin is unable to increase beta-cell division.[4] Furthermore, studies in betatrophin/Angptl8 knock-out mice do not support a role of betatrophin in controlling beta cell growth, yet point to a clear role in regulating plasma triglyceride levels.[5] Based on these studies, it is fairly safe to say that the notion that betatrophin promotes beta cell expansion is dead, which was made official by the retraction of the original paper.[4][6] Deletion of betatrophin/Angptl8 does not seem to impact glucose and insulin tolerance in mice.[7]
The encoded 22 kDa protein contains an N-terminal secretion signal and two coiled-coil domains and is a member of the angiopoietin-like (ANGPTL) protein family. However, in contrast to other ANGPTL proteins, betatrophin lacks the C-terminal fibrinogen-like domain, and therefore it is an atypical member of the ANGPTL family.[8] It shares with Angptl4 and Angptl3 the ability to inhibit the enzyme Lipoprotein lipase (LPL), and its hepatic overexpression causes elevation of circulating Triglyceride levels in mice.[9] In mice betatrophin is secreted by the liver.[9][10]
Despite having elevated post-heparin plasma LPL activity, mice lacking betatrophin/Angptl8 exhibit markedly decreased uptake of Very low-density lipoprotein-derived fatty acids into white adipose tissue (WAT).[7] The defect in fatty acids uptake by WAT in Angptl8-null mice is likely due to the enhanced fatty acids uptake by the heart and skeletal muscle, because of the elevated LPL activity in these two tissues,[11] as suggested by the ANGPTL3-4-8 model.[12]
# Structure
Three dimensional structure of none of the members of Angiopoietin like proteins (ANGPTLs) is available up till now. However, the structure of ANGPTL8 was predicted by homology modeling and is also reported in literature.[13] It consists of alpha helices and its sequence show high similarity with the coiled-coil domains of ANGPTL3 and ANGPTL4.
# Pathway
The ANGPTL8 regulatory pathway has been constructed recently by integrating the information of its know transcription factors which is available at WikiPathways data repository with the pathway id WP3915.[14]
# Clinical significance
It was hoped that betatrophin or its homolog in humans may provide an effective treatment for type 2 diabetes and perhaps even type I diabetes.[1] Unfortunately, since new data have greatly called into question the ability of betatrophin to increase beta-cell replication, its potential use as a therapy for type 2 diabetes is limited.[5] Inhibition of Angptl8 represents a possible therapeutic strategy for hypertriglyceridemia.[11] | https://www.wikidoc.org/index.php/ANGPTL8 | |
b1172c85f78a8f25835098d4f93ce3d64a1b70d7 | wikidoc | ANKRD15 | ANKRD15
KN motif and ankyrin repeat domain-containing protein 1 is a protein that in humans is encoded by the KANK1 gene.
This gene encodes a protein containing four ankyrin repeat domains in its C-terminus. The suggested role for this protein is in tumorigenesis of renal cell carcinoma.
Two alternatively spliced transcript variants encoding different isoforms have been identified. | ANKRD15
KN motif and ankyrin repeat domain-containing protein 1 is a protein that in humans is encoded by the KANK1 gene.[1][2][3]
This gene encodes a protein containing four ankyrin repeat domains in its C-terminus. The suggested role for this protein is in tumorigenesis of renal cell carcinoma.
Two alternatively spliced transcript variants encoding different isoforms have been identified.[3] | https://www.wikidoc.org/index.php/ANKRD15 | |
49b76f58c61183ab4cf70357d1a0d1465d1c74ff | wikidoc | ANKRD24 | ANKRD24
Ankyrin repeat domain-containing protein 24 is a protein in humans that is coded for by the ANKRD24 gene. The gene is also known as KIAA1981. The protein's function in humans is currently unknown. ANKRD24 is in the protein family that contains ankyrin-repeat domains.
# Gene
## Locus
The gene is located on chromosome 19 at p13.3 on the forward strand. The gene is 4041 base pairs in length and contains 29 exons. The gene is neighbored by the gene SIRT6 that encodes for the Sirtuin-6 protein and the EBI3 gene that encodes for the Epstein-Barr virus induced gene 3 protein.
## Expression
The expression pattern of ANKRD24 is uncharacterized. Under conditions of cell growth and proliferation, the expression levels increase. In germ line tumors, glioma, and prostate cancer, the expression is elevated relative to other disease states. During development, the expression level is elevated in the blastocyst stage. In adults, there are elevated levels of expression in the placenta, stomach, kidneys, and eye relative to other tissues. However, the results of experimental gene expression profiles are inconsistent relative to ANKRD24 expression, suggesting redundancy of the gene and its protein product.
# mRNA
## Alternative expression
13 transcription splice variants of ANKRD24 mRNA have been predicted.
# Protein
## General features
The ANKRD24 protein is 1146 amino acids in length, has a molecular weight of 124kDa, and has an isoelectric point of 4.98. The secondary structure is predicted to consist of all alpha helices and to not contain any beta strands. The tertiary structure of the protein is predicted to be a helical twist.
## Composition
ANKRD24 has a relatively high composition of alanine (15.0%), glutamic acid (13.5%), and leucine (11.0%) and a relatively low composition of cysteine (1.5%), phenylalanine (0.7%), tryptophan (0.2%), and tyrosine (0.8%). The protein contains positive run clusters that could be nuclear localization signals. The protein does not have any significant negative charge clusters and no significant charge patterns.
## Subcellular localization
The ANKRD24 protein is predicted to localize in the nucleus of cells.
## Domains
ANKRD24 is in the protein family that contains ankyrin-repeat domains. Ankyrin repeats are known for mediating protein-protein interactions. The protein also contains two coiled-coil regions.
## Post-translational modification
ANKRD24 is predicted to undergo C-mannosylation.
## Interacting proteins
ANKRD24 is predicted to interact with disks large homolog 4 (DLG4), eukaryotic translation elongation factor 1-alpha 1 (EEF1A1), unc-119 homolog A (UNC119), replication timing regulatory factor 1 (RIF1), protein kinase C and casein kinase substrate in neurons 1 (PACSIN1), nuclear factor NF-kappa-B p105 subunit (NFKB1), cholest-5-ene-3β,7α-diol 3β-dehydrogenase (HSD3B7), lethal giant larvae homolog 2 (L2GL2), and glucocorticoid induced 1 (GLC)CI1. No characterization of these interactions has yet to be observed.
## Homology
ANKRD24 has no human paralogs. Orthologous proteins are found in other organisms. The following table represents some of the orthologs found using searches in BLAST and BLAT. However, this list is not exhaustive for the orthologs of ANKRD24 and is only meant to display the wide diversity of species for which orthologs of ANKRD24 can be found. | ANKRD24
Ankyrin repeat domain-containing protein 24 is a protein in humans that is coded for by the ANKRD24 gene.[2] The gene is also known as KIAA1981[3]. The protein's function in humans is currently unknown. ANKRD24 is in the protein family that contains ankyrin-repeat domains.
# Gene
## Locus
The gene is located on chromosome 19 at p13.3 on the forward strand.[6][7] The gene is 4041 base pairs in length and contains 29 exons.[5][8] The gene is neighbored by the gene SIRT6 that encodes for the Sirtuin-6 protein and the EBI3 gene that encodes for the Epstein-Barr virus induced gene 3 protein.[9]
## Expression
The expression pattern of ANKRD24 is uncharacterized. Under conditions of cell growth and proliferation, the expression levels increase. In germ line tumors, glioma, and prostate cancer, the expression is elevated relative to other disease states. During development, the expression level is elevated in the blastocyst stage. In adults, there are elevated levels of expression in the placenta, stomach, kidneys, and eye relative to other tissues.[10] However, the results of experimental gene expression profiles are inconsistent relative to ANKRD24 expression, suggesting redundancy of the gene and its protein product.
# mRNA
## Alternative expression
13 transcription splice variants of ANKRD24 mRNA have been predicted.[11]
# Protein
## General features
The ANKRD24 protein is 1146 amino acids in length, has a molecular weight of 124kDa, and has an isoelectric point of 4.98.[12] The secondary structure is predicted to consist of all alpha helices and to not contain any beta strands.[13] The tertiary structure of the protein is predicted to be a helical twist.[1]
## Composition
ANKRD24 has a relatively high composition of alanine (15.0%), glutamic acid (13.5%), and leucine (11.0%) and a relatively low composition of cysteine (1.5%), phenylalanine (0.7%), tryptophan (0.2%), and tyrosine (0.8%). The protein contains positive run clusters that could be nuclear localization signals. The protein does not have any significant negative charge clusters and no significant charge patterns.[14]
## Subcellular localization
The ANKRD24 protein is predicted to localize in the nucleus of cells.[15]
## Domains
ANKRD24 is in the protein family that contains ankyrin-repeat domains. Ankyrin repeats are known for mediating protein-protein interactions.[16] The protein also contains two coiled-coil regions.[17]
## Post-translational modification
ANKRD24 is predicted to undergo C-mannosylation.[18]
## Interacting proteins
ANKRD24 is predicted to interact with disks large homolog 4 (DLG4), eukaryotic translation elongation factor 1-alpha 1 (EEF1A1), unc-119 homolog A (UNC119), replication timing regulatory factor 1 (RIF1), protein kinase C and casein kinase substrate in neurons 1 (PACSIN1), nuclear factor NF-kappa-B p105 subunit (NFKB1), cholest-5-ene-3β,7α-diol 3β-dehydrogenase (HSD3B7), lethal giant larvae homolog 2 (L2GL2), and glucocorticoid induced 1 (GLC)CI1.[19][20][21][22] No characterization of these interactions has yet to be observed.[23]
## Homology
ANKRD24 has no human paralogs. Orthologous proteins are found in other organisms. The following table represents some of the orthologs found using searches in BLAST[25] and BLAT.[26] However, this list is not exhaustive for the orthologs of ANKRD24 and is only meant to display the wide diversity of species for which orthologs of ANKRD24 can be found. | https://www.wikidoc.org/index.php/ANKRD24 | |
c6eb2b67a10a802b735530b9484abd48e51cdd27 | wikidoc | ANKRD26 | ANKRD26
Ankyrin repeat domain-containing protein 26 is a protein that in humans is encoded by the ANKRD26 gene. This protein has a function that is not currently understood.
Ankyrin repeat domain-containing protein 26 is a protein that in humans is encoded by the ANKRD26 gene.
# Gene
ANKRD26 is found on chromosome 10, at 10q21. It has 6816 base pairs in the reference sequence mRNA transcript.
## Neighborhood
LOC100289548 (PUTAETIVE UNCHARACTERIZED PROTEIN C10ORF52-LIKE) is located directly to the left (3') of ANKRD26, and is a protein coding gene located at 10p12.1. It has an unknown function. On the other side of LOC100289548 is NCRNA00202 non-protein coding RNA 202. On the 5' end of ANKRD26, YME1L1 can be found at 10q14.1. The protein encoded by the YME1-like 1 is an ortholog of yeast mitochondrial AAAmetalloprotease. This gene is thought to play a role in mitochondrial protein metabolism. On the positive strand of human chromosome ten, located next to the 5' end of ANKRD26 is MASTL, microtubule associated serine/threonine kinase-like. This particular gene encodes the microtubule associated serine/threonine kinase.1 Mutations within these gene have been expected to be associated with thrombocytopenia-2.
# Protein
Ankyrin repeat domain-containing protein 26 has three conserved domains: ANK, SbcC, and DUF3496. ANK conserved domain is located from amino acid 74-199. Ankyrin repeats are found to mediate protein-protein interactions, and also contains two antiparallel helices, as well as a beta-hairpin. SbcC conserved domain can be found from amino acid 743-1333, and is domain associated with ATPase involved in DNA repair. There is also a domain of unknown function from amino acid 1538-1649.
# Expression
In humans ANKRD26 was seen to be most highly expressed in the ear, lymph, esophagus, parathyroid, and placenta, as well as, most commonly seen in esophageal tumors and lymphoma, as well as seen in the blastocyst, fetus, juvenile, and adult developmental stages. In humans this is associated at all stages of life with lymphoma cancer as well as esophageal tumors. The association with expression in tissues and disease states doesn't show enough difference to link one another. | ANKRD26
Ankyrin repeat domain-containing protein 26 is a protein that in humans is encoded by the ANKRD26 gene.[1][2] This protein has a function that is not currently understood.
Ankyrin repeat domain-containing protein 26 is a protein that in humans is encoded by the ANKRD26 gene.[3]
# Gene
ANKRD26 is found on chromosome 10, at 10q21. It has 6816 base pairs in the reference sequence mRNA transcript.[4]
## Neighborhood[5]
LOC100289548 (PUTAETIVE UNCHARACTERIZED PROTEIN C10ORF52-LIKE) is located directly to the left (3') of ANKRD26, and is a protein coding gene located at 10p12.1.[5] It has an unknown function. On the other side of LOC100289548 is NCRNA00202 non-protein coding RNA 202.[6] On the 5' end of ANKRD26, YME1L1 can be found at 10q14.1. The protein encoded by the YME1-like 1 is an ortholog of yeast mitochondrial AAAmetalloprotease.[7] This gene is thought to play a role in mitochondrial protein metabolism.[7] On the positive strand of human chromosome ten, located next to the 5' end of ANKRD26 is MASTL, microtubule associated serine/threonine kinase-like. This particular gene encodes the microtubule associated serine/threonine kinase.1 Mutations within these gene have been expected to be associated with thrombocytopenia-2.[8]
# Protein [9]
Ankyrin repeat domain-containing protein 26 has three conserved domains: ANK, SbcC, and DUF3496. ANK conserved domain is located from amino acid 74-199. Ankyrin repeats are found to mediate protein-protein interactions, and also contains two antiparallel helices, as well as a beta-hairpin. SbcC conserved domain can be found from amino acid 743-1333, and is domain associated with ATPase involved in DNA repair. There is also a domain of unknown function from amino acid 1538-1649.
# Expression[10]
In humans ANKRD26 was seen to be most highly expressed in the ear, lymph, esophagus, parathyroid, and placenta, as well as, most commonly seen in esophageal tumors and lymphoma, as well as seen in the blastocyst, fetus, juvenile, and adult developmental stages. In humans this is associated at all stages of life with lymphoma cancer as well as esophageal tumors. The association with expression in tissues and disease states doesn't show enough difference to link one another.[10] | https://www.wikidoc.org/index.php/ANKRD26 | |
2b229bf3289b7f5495b49d5d56314ae4882f117e | wikidoc | APOBEC1 | APOBEC1
Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 also known as C->U-editing enzyme APOBEC-1 is a protein that in humans is encoded by the APOBEC1 gene.
This gene encodes a member of the APOBEC protein family and the cytidine deaminase enzyme family. The encoded protein forms a multiple-protein RNA editing holoenzyme with APOBEC1 complementation factor (A1CF). This holoenzyme is involved in the editing of cytosine-to-uracil (C-to-U) nucleotide bases in apolipoprotein B and neurofibromin 1 mRNAs.
APOBEC-1 (A1) has been linked with cholesterol control, cancer development and inhibition of viral replication. Its function relies on introducing a stop codon into apolipoprotein B (ApoB) mRNA, which alters lipid metabolism in the gastrointestinal tract. The editing mechanism is highly specific. A1’s deamination of the cytosine base yields uracil, which creates a stop codon in the mRNA.
A1 has been linked with both positive and negative health effects. In rodents, it has wide tissue distribution where as in humans, it is only expressed in the small intestine.
# Gene
APOBEC1 lies on human chromosome 12.
# Function
ApoB is essential in the assembly of very low density lipoproteins from lipids, in the liver and small intestine. By editing ApoB, it forces only the smaller expression, ApoB48 to be expressed, which greatly inhibits lipoprotein production. However, A1 is currently found only at extremely low levels in the human liver and intestine, while it is highly expressed in rodents. In humans, A1 is found exclusively in gastrointestinal epithelial cells.
# Mechanism
A1 modifies the cytosine base at position 6666 on the ApoB mRNA strand through a deamination. An A1 dimer first binds to ACF, which forms the binding complex that is then able to eliminate the amine group from cytosine.
ACF binds to the mooring sequence, which puts A1 in position to edit the correct residue. By converting cytosine to uracil, A1 changes the codon from CAA, which codes for glutamine during transcription, to UAA, a stop codon. This stop codon yields the much shorter protein ApoB48 instead of ApoB100, as the mRNA is predisposed to transcript. The editing amount, or expression, of A1 performs is correlated with the insulin concentration in the nucleus, the site of modification. Tests involving A1 mutants with various deleted amino acid sequences have shown that editing activity is dependent on residues 14 to 35. Like all APOBEC proteins, A1 coordinates a zinc atom with two cysteine and one histidine residues that serve as a Lewis acid. Hydrolytic deamination of the cytosine amine group then occurs, catalyzed by the proton transfer from the nearby glutamic acid residue, and the enzymatic structure is conserved by a proline residue.
# Structure
The structure of A1 relies on three dimensional folds induced by a zinc complex. These folds allow the enzyme to access the RNA specifically. Deletion tests with mutant strands have shown that residues 181 to 210 are integral to mRNA editing, and there is most likely a beta-turn at proline residues 190 and 191. Specifically, L182, I185, and L189 are integral to the complex’s function, most likely due to their importance to dimerization. Substituting these residues has no predicted impact on secondary structure, so the significant decrease in editing activity is best explained by the alteration of the side-chains, which are integral to dimer structure. Amino acid replacements at these sites deactivated deamination. The C-terminal of enzyme structure is more strongly expressed in the nucleus, hence the site of modification, while the 181 to 210 residues indicate that the enzyme is in the cytoplasm. These are regulatory factors.
# Disease relevance
The low levels of A1 in humans are one reason why high lipid intake is damaging to health. ApoB48 is essential for the assembly and secretion of triglyceride-rich chylomicrons, which are necessary as a response to high-fat intake. ApoB100 are metabolized in the bloodstream to LDL cholesterol, high levels of which are associated with artherosclerosis. While A1 has a negligible impact on human lipid synthesis, at high concentrations it can be genotoxic. Its diffusion toward the nucleic membrane can lead it to mutate DNA sequences that are actively transcribed on the genome. In single growth assays, A1 has been found to impact HIV replications. Additionally, A1 has reduced Hepatitis B virus (HBV) DNA replication, although the mechanism is still not known. The antiviral properties of A1 extend to both DNA and RNA due to its deamination function, which can hinder DNA replication and consequently suppress further infection by HIV or HBV. There has also been evidence that A1 also edits at NF1, related to tumors in nerve cells.
# Interactions
APOBEC1 has been shown to interact with:
- ACF
- BAG4, and
- SYNCRIP. | APOBEC1
Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 also known as C->U-editing enzyme APOBEC-1 is a protein that in humans is encoded by the APOBEC1 gene.[1]
This gene encodes a member of the APOBEC protein family and the cytidine deaminase enzyme family. The encoded protein forms a multiple-protein RNA editing holoenzyme with APOBEC1 complementation factor (A1CF). This holoenzyme is involved in the editing of cytosine-to-uracil (C-to-U) nucleotide bases in apolipoprotein B and neurofibromin 1 mRNAs.[1]
APOBEC-1 (A1) has been linked with cholesterol control, cancer development and inhibition of viral replication.[2] Its function relies on introducing a stop codon into apolipoprotein B (ApoB) mRNA, which alters lipid metabolism in the gastrointestinal tract. The editing mechanism is highly specific. A1’s deamination of the cytosine base yields uracil, which creates a stop codon in the mRNA.
A1 has been linked with both positive and negative health effects. In rodents, it has wide tissue distribution where as in humans, it is only expressed in the small intestine.[3]
# Gene
APOBEC1 lies on human chromosome 12.[4]
# Function
ApoB is essential in the assembly of very low density lipoproteins from lipids, in the liver and small intestine.[3] By editing ApoB, it forces only the smaller expression, ApoB48 to be expressed, which greatly inhibits lipoprotein production. However, A1 is currently found only at extremely low levels in the human liver and intestine, while it is highly expressed in rodents. In humans, A1 is found exclusively in gastrointestinal epithelial cells.[2]
# Mechanism
A1 modifies the cytosine base at position 6666 on the ApoB mRNA strand through a deamination.[5] An A1 dimer first binds to ACF, which forms the binding complex that is then able to eliminate the amine group from cytosine.
ACF binds to the mooring sequence, which puts A1 in position to edit the correct residue.[6] By converting cytosine to uracil, A1 changes the codon from CAA, which codes for glutamine during transcription, to UAA, a stop codon.[7] This stop codon yields the much shorter protein ApoB48 instead of ApoB100, as the mRNA is predisposed to transcript.[8] The editing amount, or expression, of A1 performs is correlated with the insulin concentration in the nucleus, the site of modification.[9][10] Tests involving A1 mutants with various deleted amino acid sequences have shown that editing activity is dependent on residues 14 to 35. Like all APOBEC proteins, A1 coordinates a zinc atom with two cysteine and one histidine residues that serve as a Lewis acid. Hydrolytic deamination of the cytosine amine group then occurs, catalyzed by the proton transfer from the nearby glutamic acid residue, and the enzymatic structure is conserved by a proline residue.[6]
# Structure
The structure of A1 relies on three dimensional folds induced by a zinc complex.[11] These folds allow the enzyme to access the RNA specifically. Deletion tests with mutant strands have shown that residues 181 to 210 are integral to mRNA editing, and there is most likely a beta-turn at proline residues 190 and 191.[6] Specifically, L182, I185, and L189 are integral to the complex’s function, most likely due to their importance to dimerization.[6] Substituting these residues has no predicted impact on secondary structure, so the significant decrease in editing activity is best explained by the alteration of the side-chains, which are integral to dimer structure.[6] Amino acid replacements at these sites deactivated deamination. The C-terminal of enzyme structure is more strongly expressed in the nucleus, hence the site of modification, while the 181 to 210 residues indicate that the enzyme is in the cytoplasm. These are regulatory factors.[12]
# Disease relevance
The low levels of A1 in humans are one reason why high lipid intake is damaging to health. ApoB48 is essential for the assembly and secretion of triglyceride-rich chylomicrons, which are necessary as a response to high-fat intake. ApoB100 are metabolized in the bloodstream to LDL cholesterol,[13] high levels of which are associated with artherosclerosis.[14] While A1 has a negligible impact on human lipid synthesis, at high concentrations it can be genotoxic. Its diffusion toward the nucleic membrane can lead it to mutate DNA sequences that are actively transcribed on the genome. In single growth assays, A1 has been found to impact HIV replications. Additionally, A1 has reduced Hepatitis B virus (HBV) DNA replication, although the mechanism is still not known. The antiviral properties of A1 extend to both DNA and RNA due to its deamination function, which can hinder DNA replication and consequently suppress further infection by HIV or HBV.[15] There has also been evidence that A1 also edits at NF1, related to tumors in nerve cells.[16]
# Interactions
APOBEC1 has been shown to interact with:
- ACF[17][18]
- BAG4,[19] and
- SYNCRIP.[20] | https://www.wikidoc.org/index.php/APOBEC1 | |
8c2299c02cc26c6530f5d415b690709481528f6a | wikidoc | APOBEC4 | APOBEC4
C->U-editing enzyme APOBEC-4, also known as Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 4, is a protein that in humans is encoded by the APOBEC4 gene. It is primarily expressed in testis and found in mammals, chicken, but not fishes.
# Function
This gene encodes a member of the AID / APOBEC family of polynucleotide (deoxy)cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection.
A recent study on APOBEC4 (A4) revealed an interesting finding that A4 enhanced the replication of HIV-1 through boosting promoter activity, it also increased the expression of other relevant promoter mediated enhanced protein expression. Biochemical analysis of A4 showed the lack of cytidine deaminase activity on single stranded DNA and it binds DNA rather weak. | APOBEC4
C->U-editing enzyme APOBEC-4, also known as Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 4, is a protein that in humans is encoded by the APOBEC4 gene. It is primarily expressed in testis and found in mammals, chicken, but not fishes.[1][2]
# Function
This gene encodes a member of the AID / APOBEC family of polynucleotide (deoxy)cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection.[2]
A recent study on APOBEC4 (A4) revealed an interesting finding that A4 enhanced the replication of HIV-1 through boosting promoter activity, it also increased the expression of other relevant promoter mediated enhanced protein expression. Biochemical analysis of A4 showed the lack of cytidine deaminase activity on single stranded DNA and it binds DNA rather weak.[3] | https://www.wikidoc.org/index.php/APOBEC4 | |
78d90ea6c8198a8067fc7d71fccc73d286a9f1ac | wikidoc | ARFGAP1 | ARFGAP1
ADP-ribosylation factor GTPase-activating protein 1 is an enzyme that in humans is encoded by the ARFGAP1 gene. Two transcript variants encoding different isoforms have been found for this gene.
# Function
The protein encoded by this gene is a GTPase-activating protein (GAP) which associates with the Golgi apparatus and which interacts with ADP-ribosylation factor 1 (ARF1). The encoded protein promotes hydrolysis of ARF1-bound GTP and is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. The activity of this protein is stimulated by phosphoinositides and inhibited by phosphatidylcholine.
The protein has two amphipathic lipid packing sensor motifs (ALPS), that let the protein sense the curvature of the membrane (<30 nm) or lipid packing defects, and in this way evaluate if the vesicle is mature and ready for coat disassembly.
# Interactions
ARFGAP1 has been shown to interact with KDELR1 and LRRK2. | ARFGAP1
ADP-ribosylation factor GTPase-activating protein 1 is an enzyme that in humans is encoded by the ARFGAP1 gene.[1][2] Two transcript variants encoding different isoforms have been found for this gene.
# Function
The protein encoded by this gene is a GTPase-activating protein (GAP) which associates with the Golgi apparatus and which interacts with ADP-ribosylation factor 1 (ARF1). The encoded protein promotes hydrolysis of ARF1-bound GTP and is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. The activity of this protein is stimulated by phosphoinositides and inhibited by phosphatidylcholine.[2]
The protein has two amphipathic lipid packing sensor motifs (ALPS), that let the protein sense the curvature of the membrane (<30 nm) or lipid packing defects, and in this way evaluate if the vesicle is mature and ready for coat disassembly.[3][4]
# Interactions
ARFGAP1 has been shown to interact with KDELR1 and LRRK2.[5][6][7] | https://www.wikidoc.org/index.php/ARFGAP1 | |
37fe0a553d37e089b6d986fd8ba96528155c2470 | wikidoc | ARFGEF1 | ARFGEF1
Brefeldin A-inhibited guanine nucleotide-exchange protein 1 is a protein that in humans is encoded by the ARFGEF1 gene.
# Function
ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP. It contains a Sec7 domain, which may be responsible for the guanine-nucleotide exchange activity and also the brefeldin A inhibition.
# Interactions
ARFGEF1 has been shown to interact with FKBP2, ARFGEF2 and PRKAR1A. | ARFGEF1
Brefeldin A-inhibited guanine nucleotide-exchange protein 1 is a protein that in humans is encoded by the ARFGEF1 gene.[1][2][3]
# Function
ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP. It contains a Sec7 domain, which may be responsible for the guanine-nucleotide exchange activity and also the brefeldin A inhibition.[3]
# Interactions
ARFGEF1 has been shown to interact with FKBP2,[4] ARFGEF2[5] and PRKAR1A.[6] | https://www.wikidoc.org/index.php/ARFGEF1 | |
f717e6ad5bbe4b05c23dc5b4494334a17ad2359c | wikidoc | ARFGEF2 | ARFGEF2
Brefeldin A-inhibited guanine nucleotide-exchange protein 2 is a protein that in humans is encoded by the ARFGEF2 gene.
# Function
ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP and is involved in Golgi transport. It contains a Sec7 domain, which may be responsible for its guanine-nucleotide exchange activity and also brefeldin A inhibition.
# Interactions
ARFGEF2 has been shown to interact with ARFGEF1, PRKAR1A and PRKAR2A. | ARFGEF2
Brefeldin A-inhibited guanine nucleotide-exchange protein 2 is a protein that in humans is encoded by the ARFGEF2 gene.[1][2]
# Function
ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP and is involved in Golgi transport. It contains a Sec7 domain, which may be responsible for its guanine-nucleotide exchange activity and also brefeldin A inhibition.[2]
# Interactions
ARFGEF2 has been shown to interact with ARFGEF1,[3] PRKAR1A[4] and PRKAR2A.[4] | https://www.wikidoc.org/index.php/ARFGEF2 | |
cf1f73f0d1c06888e2ed7c044a8ebde6946d28f6 | wikidoc | ARHGAP5 | ARHGAP5
Rho GTPase-activating protein 5 is an enzyme that in humans is encoded by the ARHGAP5 gene.
# Function
Rho GTPase activating protein 5 negatively regulates RHO GTPases, a family that may mediate cytoskeleton changes by stimulating the hydrolysis of bound GTP. Two transcript variants encoding different isoforms have been found for this gene.
# Interactions
ARHGAP5 has been shown to interact with Rnd1, Rnd2, Rnd3 and RHOA. | ARHGAP5
Rho GTPase-activating protein 5 is an enzyme that in humans is encoded by the ARHGAP5 gene.[1][2]
# Function
Rho GTPase activating protein 5 negatively regulates RHO GTPases, a family that may mediate cytoskeleton changes by stimulating the hydrolysis of bound GTP. Two transcript variants encoding different isoforms have been found for this gene.[2]
# Interactions
ARHGAP5 has been shown to interact with Rnd1,[3] Rnd2,[3] Rnd3[3] and RHOA.[3] | https://www.wikidoc.org/index.php/ARHGAP5 | |
ae59b2b5dbbdb51c06697caeb39da0f9bc51860c | wikidoc | ARHGDIB | ARHGDIB
Rho GDP-dissociation inhibitor 2 is a protein that in humans is encoded by the ARHGDIB gene. Aliases of this gene include RhoGDI2, GDID4, Rho GDI 2, and others.
# Interactions
ARHGDIB has been shown to interact with VAV1 and Src.
# Gene family
RhoGDI2 (ARHGDIB) is part of a family of three members: RhoGDI1, RhoGDI2 (also known as RhoGDIB, D4-GDI or Ly-GDI) and RhoGDI3. RhoGDI1 is expressed in many organs and is the best studied member of the family. RhoGDI2 was initially believed to be expressed specifically in blood forming cells, but has subsequently been found to be highly expressed in a variety of other cell types as well. RhoGDI3 is predominantly expressed in brain, lung, kidney, testis and pancreas, and is targeted to specific parts of the cell such as the Golgi where it may play a role in transport or proteins in cells.
# Disease involvement
Despite a high degree of sequence similarity, RhoGDI1 and RhoGDI2 are very different in their binding affinities for specific GTPases, and more importantly, in their roles in tumor formation and spread of tumor to other organs (the process of metastasis). For example, RhoGDI2 functions as a suppressor of metastasis but not a tumor suppressor in bladder cancer cells, while RhoGDI1 is a ubiquitous suppressor of tumor growth in all sites so far examined in bladder cancer models), suggesting that their cellular functions must diverge to cause these differential effects.
While there are clear links between the alteration of RhoGDI2 protein levels and disease progression and/or metastasis in several types of cancer, the mechanistic underpinnings of the mode of RhoGDI2 action under carcinogenic cellular conditions are only now beginning to be understood. Evidence demonstrates that RhoGDI2 inhibits the endothelin axis and crosstalk with macrophages within the micrometastatic microenvironment to inhibit metastatic outgrowth. As such, RhoGDI2 could prove important in the regulation of tumor dormancy. Targeting this axis with orally available endothelin receptor antagonists may prove efficacious in mimicking the inhibitory role of RhoGDI2 by preventing macrophage infiltration into the micrometastatic niche. Recent work has also determined that genetic and pharmacologic targeting of chemokine (C-C motif) ligand 2 (CCL2) also known as monocyte chemotactic protein-1 (MCP-1) or small inducible cytokine A2, its receptor CCR2 and pharmacologic ablation of macrophages can also phenocopy the effect of RhoGDI2 expression to prevent metastatic colonization of the lung67 and that RhoGDI2 is suppressor of versican, a protein that has been shown to promote cell migration and metastasis in several tumor models.
In contrast to its role as a metastasis suppressor in bladder cancer, in breast, RhoGDI2 expression has been reported to be upregulated in cancer and to promote invasion of breast cancer cells, while another report found a biphasic expression pattern of RhoGDI2 in breast cancer with decreased expression correlating with lymph node metastasis. | ARHGDIB
Rho GDP-dissociation inhibitor 2 is a protein that in humans is encoded by the ARHGDIB gene.[1][2][3] Aliases of this gene include RhoGDI2, GDID4, Rho GDI 2, and others.[4]
# Interactions
ARHGDIB has been shown to interact with VAV1[5] and Src.[6]
# Gene family
RhoGDI2 (ARHGDIB) is part of a family of three members: RhoGDI1, RhoGDI2 (also known as RhoGDIB, D4-GDI or Ly-GDI) and RhoGDI3. RhoGDI1 is expressed in many organs and is the best studied member of the family.[7][8][9] RhoGDI2 was initially believed to be expressed specifically in blood forming cells,[2] but has subsequently been found to be highly expressed in a variety of other cell types as well.[10] RhoGDI3 is predominantly expressed in brain, lung, kidney, testis and pancreas,[11][12] and is targeted to specific parts of the cell such as the Golgi where it may play a role in transport or proteins in cells.[13][14]
# Disease involvement
Despite a high degree of sequence similarity, RhoGDI1 and RhoGDI2 are very different in their binding affinities for specific GTPases,[15] and more importantly, in their roles in tumor formation and spread of tumor to other organs (the process of metastasis).[16] For example, RhoGDI2 functions as a suppressor of metastasis but not a tumor suppressor in bladder cancer cells,[10][17] while RhoGDI1 is a ubiquitous suppressor of tumor growth in all sites so far examined in bladder cancer models),[18] suggesting that their cellular functions must diverge to cause these differential effects.
While there are clear links between the alteration of RhoGDI2 protein levels and disease progression and/or metastasis in several types of cancer, the mechanistic underpinnings of the mode of RhoGDI2 action under carcinogenic cellular conditions are only now beginning to be understood. Evidence demonstrates that RhoGDI2 inhibits the endothelin axis and crosstalk with macrophages within the micrometastatic microenvironment to inhibit metastatic outgrowth.[19] As such, RhoGDI2 could prove important in the regulation of tumor dormancy. Targeting this axis with orally available endothelin receptor antagonists[20] may prove efficacious in mimicking the inhibitory role of RhoGDI2 by preventing macrophage infiltration into the micrometastatic niche.[21] Recent work has also determined that genetic and pharmacologic targeting of chemokine (C-C motif) ligand 2 (CCL2) also known as monocyte chemotactic protein-1 (MCP-1) or small inducible cytokine A2, its receptor CCR2 and pharmacologic ablation of macrophages can also phenocopy the effect of RhoGDI2 expression to prevent metastatic colonization of the lung67 and that RhoGDI2 is suppressor of versican, a protein that has been shown to promote cell migration[22] and metastasis in several tumor models.
In contrast to its role as a metastasis suppressor in bladder cancer, in breast, RhoGDI2 expression has been reported to be upregulated in cancer[23] and to promote invasion of breast cancer cells,[24] while another report found a biphasic expression pattern of RhoGDI2 in breast cancer with decreased expression correlating with lymph node metastasis.[25] | https://www.wikidoc.org/index.php/ARHGDIB | |
50e8ee1bfad70c07892b17277b862b573d99684d | wikidoc | ARHGEF4 | ARHGEF4
Rho guanine nucleotide exchange factor 4 is a protein that in humans is encoded by the ARHGEF4 gene.
# Function
Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein-coupled receptors. The encoded protein may form complex with G proteins and stimulate Rho-dependent signals. This protein is similar to rat collybistin protein. Alternative splicing of this gene generates two transcript variants that encode different isoforms. Also, there is possibility for the usage of multiple polyadenylation sites for this gene.
# Model organisms
Model organisms have been used in the study of ARHGEF4 function. A conditional knockout mouse line, called Arhgef4tm1a(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 two tests were carried out on homozygous mutant mice and one significant abnormality was observed: males has atypical peripheral blood lymphocyte parameters, including a decreased B cell number and an increased granulocyte number.
# Interactions
ARHGEF4 has been shown to interact with APC. | ARHGEF4
Rho guanine nucleotide exchange factor 4 is a protein that in humans is encoded by the ARHGEF4 gene.[1][2]
# Function
Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein-coupled receptors. The encoded protein may form complex with G proteins and stimulate Rho-dependent signals. This protein is similar to rat collybistin protein. Alternative splicing of this gene generates two transcript variants that encode different isoforms. Also, there is possibility for the usage of multiple polyadenylation sites for this gene.[2]
# Model organisms
Model organisms have been used in the study of ARHGEF4 function. A conditional knockout mouse line, called Arhgef4tm1a(KOMP)Wtsi[10][11] 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.[12][13][14]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[8][15] Twenty two tests were carried out on homozygous mutant mice and one significant abnormality was observed: males has atypical peripheral blood lymphocyte parameters, including a decreased B cell number and an increased granulocyte number.[8]
# Interactions
ARHGEF4 has been shown to interact with APC.[16] | https://www.wikidoc.org/index.php/ARHGEF4 | |
af229b3580bed034b64be07fd8bea89626f06b65 | wikidoc | ARL6IP4 | ARL6IP4
ADP-ribosylation-like factor 6 interacting protein 4 (ARL6IP4), also called SRp25 is the gene product of the ARL6IP4 gene located on chromosome 12q24.31.It is 360 amino acids in length.It is expressed ubiquitously but only in G1/S phase of the cell cycle. The human and mouse mRNA of this protein have 77% homology.
# Structure
Two types of amino acid clusters have been observed, a serine cluster and a basic cluster.
# Function
The function of this protein is unknown.However, due to sequence homology of the protein with SR splicing factors it is widely believed that the protein is nuclear and may have a role in splicing regulation. The protein is also believed to be a mediator in the RAC1 signalling pathway.
# RNA editing
The pre-mRNA of the ARL6IP4 gene product is subject to RNA Editing.
## Type
A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine.Inosines are recognised as guanosine by the cells translational machinery.There are three members of the ADAR family ADARs 1-3 with ADAR 1 and ADAR 2 being the only enzymatically active members.ADAR3 is thought to have a regulatory role in the brain.ADAR1 and ADAR 2 are widely expressed in tissues while ADAR 3 is restricted to the brain.The double stranded regions of RNA are formed by base-pairing between residues in the region close to the editing site with residues usually in a neighboring intron but can be an exonic sequence.The region that base pairs with the editing region is known as an Editing Complementary Sequence(ECS)
## Location
Editing occurs at a K/R editing site within amino acid position 225 of the final protein.Using RT-PCR and sequencing of 100 individual clones, 7% of isoform 3 of the protein showed a G instead of an A at this position during sequencing. Other minor editing sites may be potentially present including some in the same exon as the major editing site.Like in the case of IGFBP7 pre-mRNA,editing is unusual as the RNA fold back structure is made up off exonic sequence only.
## Effects on protein structure
Editing at this site results in a codon changed from a Lysine to an Arginine.This occurs in a highly basic region of the protein.
## Effects on protein function
The function of the unedited protein is largely uncharacterised.Therefore, the effect of editing on the pre-mRNA on the proteins function is also unknown.The amino acid change is conservative and is unlikely to massively alter protein function. However,the editing site maybe important since the amino acid being altered is a Lysine, which may be involved in the regulation of protein expression. Lysines can be sites of post-translational modification and the conversion of Lysine to an Arginine could affect post translational modification. | ARL6IP4
ADP-ribosylation-like factor 6 interacting protein 4 (ARL6IP4), also called SRp25 is the gene product of the ARL6IP4 gene located on chromosome 12q24.31.It is 360 amino acids in length.It is expressed ubiquitously but only in G1/S phase of the cell cycle.[1] The human and mouse mRNA of this protein have 77% homology.[2]
# Structure
Two types of amino acid clusters have been observed, a serine cluster and a basic cluster.[2]
# Function
The function of this protein is unknown.However, due to sequence homology of the protein with SR splicing factors it is widely believed that the protein is nuclear and may have a role in splicing regulation.[2] The protein is also believed to be a mediator in the RAC1 signalling pathway.[3]
# RNA editing
The pre-mRNA of the ARL6IP4 gene product is subject to RNA Editing.[4]
## Type
A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine.Inosines are recognised as guanosine by the cells translational machinery.There are three members of the ADAR family ADARs 1-3 with ADAR 1 and ADAR 2 being the only enzymatically active members.ADAR3 is thought to have a regulatory role in the brain.ADAR1 and ADAR 2 are widely expressed in tissues while ADAR 3 is restricted to the brain.The double stranded regions of RNA are formed by base-pairing between residues in the region close to the editing site with residues usually in a neighboring intron but can be an exonic sequence.The region that base pairs with the editing region is known as an Editing Complementary Sequence(ECS)
## Location
Editing occurs at a K/R editing site within amino acid position 225 of the final protein.Using RT-PCR and sequencing of 100 individual clones, 7% of isoform 3 of the protein showed a G instead of an A at this position during sequencing. Other minor editing sites may be potentially present including some in the same exon as the major editing site.Like in the case of IGFBP7 pre-mRNA,editing is unusual as the RNA fold back structure is made up off exonic sequence only.[4]
## Effects on protein structure
Editing at this site results in a codon changed from a Lysine to an Arginine.This occurs in a highly basic region of the protein.[4]
## Effects on protein function
The function of the unedited protein is largely uncharacterised.Therefore, the effect of editing on the pre-mRNA on the proteins function is also unknown.The amino acid change is conservative and is unlikely to massively alter protein function. However,the editing site maybe important since the amino acid being altered is a Lysine, which may be involved in the regulation of protein expression. Lysines can be sites of post-translational modification and the conversion of Lysine to an Arginine could affect post translational modification.[4] | https://www.wikidoc.org/index.php/ARL6IP4 | |
0cb30be6e97735cd974f4440a945f279a54e6382 | wikidoc | ATG16L1 | ATG16L1
Autophagy-related protein 16-1 is a protein that in humans is encoded by the ATG16L1 gene.
# Function
Autophagy is the major intracellular degradation system delivering cytoplasmic components to lysosomes, and it accounts for degradation of most long-lived proteins and some organelles. Cytoplasmic constituents, including organelles, are sequestered into double-membraned autophagosomes, which subsequently fuse with lysosomes. ATG16L1 is a component of a large protein complex essential for autophagy.
# Clinical significance
Mutations in the ATG16L1 gene may be linked to Crohn's disease. | ATG16L1
Autophagy-related protein 16-1 is a protein that in humans is encoded by the ATG16L1 gene.[1]
# Function
Autophagy is the major intracellular degradation system delivering cytoplasmic components to lysosomes, and it accounts for degradation of most long-lived proteins and some organelles. Cytoplasmic constituents, including organelles, are sequestered into double-membraned autophagosomes, which subsequently fuse with lysosomes. ATG16L1 is a component of a large protein complex essential for autophagy.[2][3]
# Clinical significance
Mutations in the ATG16L1 gene may be linked to Crohn's disease.[4][5][6] | https://www.wikidoc.org/index.php/ATG16L1 | |
053233c0ec479ab38b394c2c32575398367153b9 | wikidoc | ATP5F1A | ATP5F1A
ATP synthase F1 subunit alpha, mitochondrial is an enzyme that in humans is encoded by the ATP5F1A gene.
# Function
This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, using an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the alpha subunit of the catalytic core. Alternatively spliced transcript variants encoding the same protein have been identified. Pseudogenes of this gene are located on chromosomes 9, 2, and 16.
# Structure
The ATP5F1A gene, located on the q arm of chromosome 18 in position 21, is made up of 13 exons and is 20,090 base pairs in length. The ATP5F1A protein weighs 59.7 kDa and is composed of 553 amino acids. The protein is a subunit of the catalytic portion of the F1Fo ATPase, also known as Complex V, which consists of 14 nuclear and 2 mitochondrial -encoded subunits. As an alpha subunit, ATP5F1A is contained within the catalytic F1 portion of the complex. The nomenclature of the enzyme has a long history. The F1 fraction derives its name from the term "Fraction 1" and Fo (written as a subscript letter "o", not "zero") derives its name from being the binding fraction for oligomycin, a type of naturally-derived antibiotic that is able to inhibit the Fo unit of ATP synthase. The F1 particle is large and can be seen in the transmission electron microscope by negative staining. These are particles of 9 nm diameter that pepper the inner mitochondrial membrane. They were originally called elementary particles and were thought to contain the entire respiratory apparatus of the mitochondrion, but, through a long series of experiments, Efraim Racker and his colleagues (who first isolated the F1 particle in 1961) were able to show that this particle is correlated with ATPase activity in uncoupled mitochondria and with the ATPase activity in submitochondrial particles created by exposing mitochondria to ultrasound. This ATPase activity was further associated with the creation of ATP by a long series of experiments in many laboratories.
# Function
Mitochondrial membrane ATP synthase (F1Fo ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F1 - containing the extramembraneous catalytic core, and Fo - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F1 is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F1. Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits. Subunit alpha does not bear the catalytic high-affinity ATP-binding sites.
# Clinical significance
Mutations affecting the ATP5F1A gene cause combined oxidative phosphorylation deficiency 22 (COXPD22), a mitochondrial disorder characterized by intrauterine growth retardation, microcephaly, hypotonia, pulmonary hypertension, failure to thrive, encephalopathy, and heart failure. Mutations on the ATP5F1A gene also cause mitochondrial complex V deficiency, nuclear 4 (MC5DN4), a mitochondrial disorder with heterogeneous clinical manifestations including dysmorphic features, psychomotor retardation, hypotonia, growth retardation, cardiomyopathy, enlarged liver, hypoplastic kidneys and elevated lactate levels in urine, plasma and cerebrospinal fluid.
# Model organisms
Model organisms have been used in the study of ATP5F1A function. A conditional knockout mouse line, called Atp5a1tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty two tests were carried out on mutant mice and five 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 decreased body weight, lean body mass and hypoproteinemia was observed in female animals. | ATP5F1A
ATP synthase F1 subunit alpha, mitochondrial is an enzyme that in humans is encoded by the ATP5F1A gene.[1][2]
# Function
This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, using an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the alpha subunit of the catalytic core. Alternatively spliced transcript variants encoding the same protein have been identified. Pseudogenes of this gene are located on chromosomes 9, 2, and 16.[2]
# Structure
The ATP5F1A gene, located on the q arm of chromosome 18 in position 21, is made up of 13 exons and is 20,090 base pairs in length.[2] The ATP5F1A protein weighs 59.7 kDa and is composed of 553 amino acids.[3][4] The protein is a subunit of the catalytic portion of the F1Fo ATPase, also known as Complex V, which consists of 14 nuclear and 2 mitochondrial -encoded subunits. As an alpha subunit, ATP5F1A is contained within the catalytic F1 portion of the complex.[2] The nomenclature of the enzyme has a long history. The F1 fraction derives its name from the term "Fraction 1" and Fo (written as a subscript letter "o", not "zero") derives its name from being the binding fraction for oligomycin, a type of naturally-derived antibiotic that is able to inhibit the Fo unit of ATP synthase.[5][6] The F1 particle is large and can be seen in the transmission electron microscope by negative staining.[7] These are particles of 9 nm diameter that pepper the inner mitochondrial membrane. They were originally called elementary particles and were thought to contain the entire respiratory apparatus of the mitochondrion, but, through a long series of experiments, Efraim Racker and his colleagues (who first isolated the F1 particle in 1961) were able to show that this particle is correlated with ATPase activity in uncoupled mitochondria and with the ATPase activity in submitochondrial particles created by exposing mitochondria to ultrasound. This ATPase activity was further associated with the creation of ATP by a long series of experiments in many laboratories.
# Function
Mitochondrial membrane ATP synthase (F1Fo ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F1 - containing the extramembraneous catalytic core, and Fo - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F1 is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F1. Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits. Subunit alpha does not bear the catalytic high-affinity ATP-binding sites.[8]
# Clinical significance
Mutations affecting the ATP5F1A gene cause combined oxidative phosphorylation deficiency 22 (COXPD22), a mitochondrial disorder characterized by intrauterine growth retardation, microcephaly, hypotonia, pulmonary hypertension, failure to thrive, encephalopathy, and heart failure. Mutations on the ATP5F1A gene also cause mitochondrial complex V deficiency, nuclear 4 (MC5DN4), a mitochondrial disorder with heterogeneous clinical manifestations including dysmorphic features, psychomotor retardation, hypotonia, growth retardation, cardiomyopathy, enlarged liver, hypoplastic kidneys and elevated lactate levels in urine, plasma and cerebrospinal fluid.[9]
# Model organisms
Model organisms have been used in the study of ATP5F1A function. A conditional knockout mouse line, called Atp5a1tm1a(EUCOMM)Wtsi[16][17] 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.[18][19][20]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[14][21] Twenty two tests were carried out on mutant mice and five significant abnormalities were observed.[14] 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 decreased body weight, lean body mass and hypoproteinemia was observed in female animals.[14] | https://www.wikidoc.org/index.php/ATP5F1A | |
8a963f58c98a8052e0b00805cec55621692d34a7 | wikidoc | ATP6AP2 | ATP6AP2
The renin receptor also known as ATPase H(+)-transporting lysosomal accessory protein 2, or the prorenin receptor, is a protein that in humans is encoded by the ATP6AP2 gene.
# Function
The renin receptor binds renin and prorenin. Binding of renin to this receptor induces the conversion of angiotensinogen to angiotensin I.
This protein is associated with adenosine triphosphatases (ATPases). Proton-translocating ATPases have fundamental roles in energy conservation, secondary active transport, acidification of intracellular compartments, and cellular pH homeostasis. There are three classes of ATPases- F, P, and V. The vacuolar (V-type) ATPases have a transmembrane proton-conducting sector and an extramembrane catalytic sector. This protein has been found associated with the transmembrane sector of the V-type ATPases. | ATP6AP2
The renin receptor also known as ATPase H(+)-transporting lysosomal accessory protein 2, or the prorenin receptor, is a protein that in humans is encoded by the ATP6AP2 gene.[1][2][3]
# Function
The renin receptor binds renin and prorenin. Binding of renin to this receptor induces the conversion of angiotensinogen to angiotensin I.[4]
This protein is associated with adenosine triphosphatases (ATPases). Proton-translocating ATPases have fundamental roles in energy conservation, secondary active transport, acidification of intracellular compartments, and cellular pH homeostasis. There are three classes of ATPases- F, P, and V. The vacuolar (V-type) ATPases have a transmembrane proton-conducting sector and an extramembrane catalytic sector. This protein has been found associated with the transmembrane sector of the V-type ATPases.[3] | https://www.wikidoc.org/index.php/ATP6AP2 | |
2eec60398fd4a05064f67856a17226e6b8153d91 | wikidoc | ATP6V0B | ATP6V0B
V-type proton ATPase 21 kDa proteolipid subunit is an enzyme that in humans is encoded by the ATP6V0B gene.
This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits, plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c'', and d.
Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes, or alternatively spliced transcript variants. This encoded protein is part of the transmembrane V0 domain, and is the human counterpart of yeast VMA16. Two alternatively spliced transcript variants that encode different proteins have been found for this gene. | ATP6V0B
V-type proton ATPase 21 kDa proteolipid subunit is an enzyme that in humans is encoded by the ATP6V0B gene.[1][2]
This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits, plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c'', and d.
Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes, or alternatively spliced transcript variants. This encoded protein is part of the transmembrane V0 domain, and is the human counterpart of yeast VMA16. Two alternatively spliced transcript variants that encode different proteins have been found for this gene.[2] | https://www.wikidoc.org/index.php/ATP6V0B | |
b8c46e10a58b5217fc6bbd0c7a5d0c963c83009c | wikidoc | ATP6V1F | ATP6V1F
V-type proton ATPase subunit F is an enzyme that in humans is encoded by the ATP6V1F gene.
This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c", and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is the V1 domain F subunit protein.
Subunit F is a 16 kDa protein that is required for the assembly and activity of V-ATPase, and has a potential role in the differential targeting and regulation of the enzyme for specific organelles. This subunit is not necessary for the rotation of the ATPase V1 rotor, but it does promote catalysis. | ATP6V1F
V-type proton ATPase subunit F is an enzyme that in humans is encoded by the ATP6V1F gene.[1][2][3]
This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c", and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is the V1 domain F subunit protein.[3]
Subunit F is a 16 kDa protein that is required for the assembly and activity of V-ATPase, and has a potential role in the differential targeting and regulation of the enzyme for specific organelles. This subunit is not necessary for the rotation of the ATPase V1 rotor, but it does promote catalysis.[4] | https://www.wikidoc.org/index.php/ATP6V1F | |
3087b0f2581cb7bc14221d7866bd05d6de9faf84 | wikidoc | AVICINE | AVICINE
# Overview
AVICINE was developed by AVI BioPharma Inc. It is a cancer vaccine which was created to cause
an immune reaction to the tumor associated antigen, human chorionic gonadotropin (hCG).
This vaccine will be designed to work by actively stimulating immunization amongst tumor cells, or tumor associated antigens. These can be the keys to unlocking the cancer cells, making way for the therapeutic values of AVICINE.
# Research behind the drug
This particular vaccine is a synthesized formulation of peptides developed to create an unstable environment for the hCG-producing cancer cells. By joining them together with diphtheria toxoids, the AVICINE peptide formulation is able to cause a specific immune response to hCG which won’t interfere with related glycoprotein hormones.
# Common elements between pregnancy and cancer
During pregnancy, women naturally generate the hCG hormone, leading scientists to believe it stimulates growth and protects the developing fetus from auto-immune attack, therefore making the pregnancy successful. Cancer cells are believed to produce hCG for the same reasons. In both Cancer and Pregnancy hCG :
- encourages rapid cell division
- musters development/reaction and tissue invasion
- promotes formation of blood vessels
- Allows tumor or fetus to cancel rejection by suppressing the immune system
An anti-hCG vaccine would result in an immune attack on tumor cells, as well as prevent them from benefiting from hCG production.
# Clinical Studies
AVICINE has been shown to be effective in blocking fertility, suggesting that it should also work in fighting cancer. These studies also note that the drug will help in patient survival. | AVICINE
# Overview
AVICINE was developed by AVI BioPharma Inc. It is a cancer vaccine which was created to cause
an immune reaction to the tumor associated antigen, human chorionic gonadotropin (hCG).
This vaccine will be designed to work by actively stimulating immunization amongst tumor cells, or tumor associated antigens. These can be the keys to unlocking the cancer cells, making way for the therapeutic values of AVICINE.
# Research behind the drug
This particular vaccine is a synthesized formulation of peptides developed to create an unstable environment for the hCG-producing cancer cells. By joining them together with diphtheria toxoids, the AVICINE peptide formulation is able to cause a specific immune response to hCG which won’t interfere with related glycoprotein hormones.
# Common elements between pregnancy and cancer
During pregnancy, women naturally generate the hCG hormone, leading scientists to believe it stimulates growth and protects the developing fetus from auto-immune attack, therefore making the pregnancy successful. Cancer cells are believed to produce hCG for the same reasons. In both Cancer and Pregnancy hCG :
- encourages rapid cell division
- musters development/reaction and tissue invasion
- promotes formation of blood vessels
- Allows tumor or fetus to cancel rejection by suppressing the immune system
An anti-hCG vaccine would result in an immune attack on tumor cells, as well as prevent them from benefiting from hCG production.
# Clinical Studies
AVICINE has been shown to be effective in blocking fertility, suggesting that it should also work in fighting cancer. These studies also note that the drug will help in patient survival.
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/AVICINE | |
ed20ba0d1e5d59a646e5950094d60055575689ef | wikidoc | AZD2171 | AZD2171
# Overview
AZD2171 (tentative trade name Recentin) is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases. It is being developed by AstraZeneca as a possible chemotherapeutic agent for oral administration.
As of 2007, it is undergoing Phase I clinical trials for the treatment of non-small cell lung cancer and colorectal cancer in adults, as well as tumors of the central nervous system in children.
# Further reading
- Wedge S, Kendrew J, Hennequin L; et al. (2005). "AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer". Cancer Res. 65 (10): 4389–400. PMID 15899831.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (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} | AZD2171
# Overview
AZD2171 (tentative trade name Recentin) is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases. It is being developed by AstraZeneca as a possible chemotherapeutic agent for oral administration.
As of 2007, it is undergoing Phase I clinical trials for the treatment of non-small cell lung cancer and colorectal cancer in adults, as well as tumors of the central nervous system in children.
# Further reading
- Wedge S, Kendrew J, Hennequin L; et al. (2005). "AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer". Cancer Res. 65 (10): 4389–400. PMID 15899831.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (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}
# External links
- AZD2171—AstraZeneca Pipeline
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/AZD2171 | |
c1d20cb8c9cd7f285b77a91305888d4234fc6152 | wikidoc | Abscess | Abscess
# Overview
Abscess is defined as collection of pus in a specific part of body. Abscess can form in any tissues secondary to initial inflammation or trauma. Skin is the most common site for abscess formation. Abscess may be classified based on pathogen. Pathogen is varied depending on abscess' location however, Staphylococcus aureus is the leading cause of abscesses. Secondary to local inflammation and cytokine release, polymorphonuclear cells (PMNs) are the first and the most important responding cells in abscess formation. Neutrophils, are responsible for phagocytosis. Once the pathogen is opsonized by complement system, it will be recognized by neutrophils and the phagocytosis process will begin. After phagocytosis the bactricidal process will begin by producing superoxide radicals and other reactive oxygen species (ROS). Conditions that may result in immunosuppresion, such as chronic steroid therapy, chemotherapy, diabetes, cancer, and AIDS are predisposing factors for abscess formation. Diagnosis is based on clinical features, laboratory, and imaging findings. Treatment depends on location and etiology and it is mostly drainage and antibiotics.
# Causes
Abscesses are caused by many different pathogens based on their anatomical location. The following table summarizes pathogenic causes of abscesses.
# Classification
Abscesses may be classified based on their location. These are listed below.
# Differential diagnosis
The following table summarizes differential diagnosis list for different abscesses. | Abscess
For patient information click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]:Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]
# Overview
Abscess is defined as collection of pus in a specific part of body. Abscess can form in any tissues secondary to initial inflammation or trauma. Skin is the most common site for abscess formation. Abscess may be classified based on pathogen. Pathogen is varied depending on abscess' location however, Staphylococcus aureus is the leading cause of abscesses. Secondary to local inflammation and cytokine release, polymorphonuclear cells (PMNs) are the first and the most important responding cells in abscess formation.[1] Neutrophils, are responsible for phagocytosis. Once the pathogen is opsonized by complement system, it will be recognized by neutrophils and the phagocytosis process will begin. After phagocytosis the bactricidal process will begin by producing superoxide radicals and other reactive oxygen species (ROS).[2] Conditions that may result in immunosuppresion, such as chronic steroid therapy, chemotherapy, diabetes, cancer, and AIDS are predisposing factors for abscess formation. Diagnosis is based on clinical features, laboratory, and imaging findings. Treatment depends on location and etiology and it is mostly drainage and antibiotics.
# Causes
Abscesses are caused by many different pathogens based on their anatomical location. The following table summarizes pathogenic causes of abscesses.[3][4][5][6][7][8][9][3][10][11][12]
# Classification
Abscesses may be classified based on their location. These are listed below.
# Differential diagnosis
The following table summarizes differential diagnosis list for different abscesses. | https://www.wikidoc.org/index.php/Abcess | |
56046660e751a3ae144afac8d7ee9ffd47813f42 | wikidoc | Abdomen | Abdomen
# Overview
The abdomen is the part of the body that lies between the chest and the thigh and encloses the ureters, intestines, liver, anus, bladder, gallbladder, and reproductive system outside the breast. It is also called the belly or venter. In humans, and in many other vertebrates, it is the region between the thorax and the pelvis (Separating the thoracic cavity and the abdominal cavity is the thoracic diaphragm). In fully developed insects, the abdomen is the third (or posterior) segment, after the head and thorax.
# Vertebrates
In vertebrates, the abdomen contains several organs:
- Part of the digestive system (gallbladder, liver, anus, appendix, rectum, and intestines),
- Part of the urinary system (ureters, bladder, urethra).
- The internal reproductive organs (ovaries, fallopian tubes, uterus, vulva, and vagina in women, testes, vas deferens, seminal vesicles, prostate, penis and urethra in men)
The abdomen also contains some of the largest and most easily accessible blood vessels in many animals, and is often used in medicine experimentation for catheterisation.
For various reasons, the abdomen is often coloured differently from the rest of the body. In animals with furry or hairy bodies, the abdomen is frequently hairless, or nearly so.
The abdomen is oval in shape and is the largest cavity in the body. It can be broken down into the lower and upper extremity. The lower extremity covers the inner surface of the bony pelvis. The Levator ani and Coccygeus are located on either side
The diaphragm forms the upper extremity and acts as a dome over the abdomen extending to the upper border of the fifth rib. It is an element in the anterior chain.
# Invertebrates
The invertebrate abdomen is built up of a series of concave upper plates known as tergites and convex lower plates known as sternites, the whole being held together by a tough yet stretchable membrane.
The abdomen contains the insect's digestive tract and reproductive organs, it consists of eleven segments in most orders of insects though the eleventh segment is absent in the adult of most higher orders. The number of these segments does vary from species to species with the number of segments visible reduced to only seven in the common honeybee. In the Collembola (Springtails) the abdomen has only six segments.
Unlike other Arthropods, insects possess no legs on the abdomen in adult form, though the Protura do have rudimentary leg-like appendages on the first three abdominal segments, and Archaeognatha possess small, articulated "styli" which are sometimes considered to be rudimentary appendages. Many larval insects including the Lepidoptera and the Symphyta (Sawflies) have fleshy appendages called prolegs on their abdominal segments (as well as their more familiar thoracic legs), which allow them to grip onto the edges of plant leaves as they walk around. | Abdomen
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
The abdomen is the part of the body that lies between the chest and the thigh and encloses the ureters, intestines, liver, anus, bladder, gallbladder, and reproductive system outside the breast. It is also called the belly or venter.[1] In humans, and in many other vertebrates, it is the region between the thorax and the pelvis (Separating the thoracic cavity and the abdominal cavity is the thoracic diaphragm). In fully developed insects, the abdomen is the third (or posterior) segment, after the head and thorax.
# Vertebrates
In vertebrates, the abdomen contains several organs:
- Part of the digestive system (gallbladder, liver, anus, appendix, rectum, and intestines),
- Part of the urinary system (ureters, bladder, urethra).
- The internal reproductive organs (ovaries, fallopian tubes, uterus, vulva, and vagina in women, testes, vas deferens, seminal vesicles, prostate, penis and urethra in men)
The abdomen also contains some of the largest and most easily accessible blood vessels in many animals, and is often used in medicine experimentation for catheterisation.
For various reasons, the abdomen is often coloured differently from the rest of the body. In animals with furry or hairy bodies, the abdomen is frequently hairless, or nearly so.
The abdomen is oval in shape and is the largest cavity in the body. It can be broken down into the lower and upper extremity. The lower extremity covers the inner surface of the bony pelvis. The Levator ani and Coccygeus are located on either side
The diaphragm forms the upper extremity and acts as a dome over the abdomen extending to the upper border of the fifth rib. It is an element in the anterior chain.
# Invertebrates
The invertebrate abdomen is built up of a series of concave upper plates known as tergites and convex lower plates known as sternites, the whole being held together by a tough yet stretchable membrane.
The abdomen contains the insect's digestive tract and reproductive organs, it consists of eleven segments in most orders of insects though the eleventh segment is absent in the adult of most higher orders. The number of these segments does vary from species to species with the number of segments visible reduced to only seven in the common honeybee. In the Collembola (Springtails) the abdomen has only six segments.
Unlike other Arthropods, insects possess no legs on the abdomen in adult form, though the Protura do have rudimentary leg-like appendages on the first three abdominal segments, and Archaeognatha possess small, articulated "styli" which are sometimes considered to be rudimentary appendages. Many larval insects including the Lepidoptera and the Symphyta (Sawflies) have fleshy appendages called prolegs on their abdominal segments (as well as their more familiar thoracic legs), which allow them to grip onto the edges of plant leaves as they walk around. | https://www.wikidoc.org/index.php/Abdomen | |
82a829488d0fc4abbf9708d96b949762de4c51c0 | wikidoc | Aboulia | Aboulia
# Overview
Aboulia or Abulia (from the Greek "αβουλία", meaning "non-will"), in neurology, refers to a lack of will or initiative. The patient is unable to act or make decisions independently. It may range in severity from subtle to overwhelming.
# Pathophysiology
Abulia may result from a variety of brain injuries which cause personality change, such as dementing illnesses, trauma, or intracerebral hemorrhage (stroke), especially stroke causing diffuse injury to the right hemisphere. Abulia has also been associated with amphetamine withdrawal.It may complicate rehabilitation when a stroke patient is uninterested in performing tasks like walking despite being capable of doing so. It should be differentiated from apraxia, when a brain injured patient has impairment in comprehending the movements necessary to perform a motor task despite not having any paralysis that prevents performing the task; that condition can also result in lack of initiation of activity.
Especially in patients with progressive dementia, it may affect feeding. Patients may continue to chew or hold food in their mouths for hours without swallowing it. The behavior may be most evident after these patients have eaten part of their meals and no longer have strong appetites. Caregivers can use sweet or salty flavored foods later in meals to provide interest and increase oral intake, but must always clear the mouth of food after each meal.
# Causes
## Common Causes
- Amphetamine withdrawal
- Dementia
- Intracerebral hemorrhage
- Traumatic brain injury
## Causes by Organ System
## Causes in Alphabetical Order
- Acute caudate vascular lesions
- Alzheimer's disease
- Amphetamine withdrawal
- Anterior cingulate circuit damage
- Capsular genu infarction
- CNS lupus
- Damage to the basal ganglia
- Dementia
- Depression
- Huntington's disease
- Hydrocephalus
- Intracerebral hemorrhage
- Multiple sclerosis
- Parkinson's disease
- Progressive supranuclear palsy
- Schizophrenia
- Traumatic brain injury | Aboulia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Ogheneochuko Ajari, MB.BS, MS [3]
# Overview
Aboulia or Abulia (from the Greek "αβουλία", meaning "non-will"), in neurology, refers to a lack of will or initiative. The patient is unable to act or make decisions independently. It may range in severity from subtle to overwhelming.
# Pathophysiology
Abulia may result from a variety of brain injuries which cause personality change, such as dementing illnesses, trauma, or intracerebral hemorrhage (stroke), especially stroke causing diffuse injury to the right hemisphere. Abulia has also been associated with amphetamine withdrawal.[1]It may complicate rehabilitation when a stroke patient is uninterested in performing tasks like walking despite being capable of doing so. It should be differentiated from apraxia, when a brain injured patient has impairment in comprehending the movements necessary to perform a motor task despite not having any paralysis that prevents performing the task; that condition can also result in lack of initiation of activity.
Especially in patients with progressive dementia, it may affect feeding. Patients may continue to chew or hold food in their mouths for hours without swallowing it. The behavior may be most evident after these patients have eaten part of their meals and no longer have strong appetites. Caregivers can use sweet or salty flavored foods later in meals to provide interest and increase oral intake, but must always clear the mouth of food after each meal.
# Causes
## Common Causes
- Amphetamine withdrawal
- Dementia
- Intracerebral hemorrhage
- Traumatic brain injury
## Causes by Organ System
## Causes in Alphabetical Order
- Acute caudate vascular lesions
- Alzheimer's disease
- Amphetamine withdrawal
- Anterior cingulate circuit damage
- Capsular genu infarction
- CNS lupus
- Damage to the basal ganglia
- Dementia
- Depression
- Huntington's disease
- Hydrocephalus
- Intracerebral hemorrhage
- Multiple sclerosis
- Parkinson's disease
- Progressive supranuclear palsy
- Schizophrenia
- Traumatic brain injury | https://www.wikidoc.org/index.php/Aboulia | |
dbacdbe6852836de97f0078e557b3ced731f1a00 | wikidoc | Aphonia | Aphonia
# Overview
Aphonia is the medical term for the inability to speak. It is considered more severe than dysphonia. A primary cause of aphonia is bilateral disruption of the recurrent laryngeal nerve, which supplies nearly all the muscles in the larynx. Damage to the nerve may be the result of surgery (e.g., thyroidectomy) or a tumor.
Aphonia means "no voice." In other words, a person with this disorder has "lost" his/her voice.
# Differentiating Aphonia from other Disorders
Functional (or psychogenic) aphonia is often seen in patients with underlying psychological problems. Laryngeal examination will show usually bowed vocal folds that fail to adduct to the midline during phonation. However, the vocal folds will adduct when the patient is asked to cough. Treatment should involve consultation and counseling with a speech pathologist and, if necessary, a psychologist.
In this case, the patient's history and the observed unilateral immobility rules out functional aphonia.
# Causes
There are many reasons why this may happen. Injuries seem to be the cause of aphonia rather frequently - minor injuries which affect the second and third dorsal area in such a manner that the lymph patches concerned with coordination become either atrophic or relatively nonfunctioning.
Basically, any injury or condition that prevents the vocal cords, the paired bands of muscle tissue positioned over the trachea, from coming together and vibrating will have the potential to make a person unable to speak. When a person prepares to speak, the vocal folds come together over the trachea and vibrate due to the airflow from the lungs. This mechanism produces the sound of the voice. If the vocal folds cannot meet together to vibrate, sound will not be produced.
Poor eliminations can bring about disturbances and sometimes are the primary cause of aphonia; this build-up of wastes within the bloodstream becomes a toxic force and makes it necessary for the body to achieve its own balance after a lapse of time. When this comes about, the throat and larynx area might be disassociated in function from the rest of the body, and the forces there bring about local inflammation in an effort to achieve balance. Fear also is often a concomitant and a contributor.
## Causes by Organ System
## Causes in Alphabetical Order
# Treatment of Aphonia
Therapy should first be aimed at correcting those conditions which might produce a disturbance in the centers of coordination between the three nervous systems. Then the overtaxed nerve forces of the body as a whole should be relieved, the incoordination which has been a factor in the disease process should be eliminated, and the forces of the body should be coordinated. The diet should be corrected and sufficient stimulus of a medicinal nature should be added to keep the body in a normal force. Some cases that are psychological - where the body is amenable to suggestion - would benefit by suggestive therapy. Attention should be paid to attitudes of mind and to ideals.
# Related Chapters
- Mute | Aphonia
Template:SignSymptom infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Aphonia is the medical term for the inability to speak. It is considered more severe than dysphonia. A primary cause of aphonia is bilateral disruption of the recurrent laryngeal nerve, which supplies nearly all the muscles in the larynx. Damage to the nerve may be the result of surgery (e.g., thyroidectomy) or a tumor.
Aphonia means "no voice." In other words, a person with this disorder has "lost" his/her voice.
# Differentiating Aphonia from other Disorders
Functional (or psychogenic) aphonia is often seen in patients with underlying psychological problems. Laryngeal examination will show usually bowed vocal folds that fail to adduct to the midline during phonation. However, the vocal folds will adduct when the patient is asked to cough. Treatment should involve consultation and counseling with a speech pathologist and, if necessary, a psychologist.
In this case, the patient's history and the observed unilateral immobility rules out functional aphonia.
# Causes
There are many reasons why this may happen. Injuries seem to be the cause of aphonia rather frequently - minor injuries which affect the second and third dorsal area in such a manner that the lymph patches concerned with coordination become either atrophic or relatively nonfunctioning.
Basically, any injury or condition that prevents the vocal cords, the paired bands of muscle tissue positioned over the trachea, from coming together and vibrating will have the potential to make a person unable to speak. When a person prepares to speak, the vocal folds come together over the trachea and vibrate due to the airflow from the lungs. This mechanism produces the sound of the voice. If the vocal folds cannot meet together to vibrate, sound will not be produced.
Poor eliminations can bring about disturbances and sometimes are the primary cause of aphonia; this build-up of wastes within the bloodstream becomes a toxic force and makes it necessary for the body to achieve its own balance after a lapse of time. When this comes about, the throat and larynx area might be disassociated in function from the rest of the body, and the forces there bring about local inflammation in an effort to achieve balance. Fear also is often a concomitant and a contributor.
## Causes by Organ System
## Causes in Alphabetical Order
# Treatment of Aphonia
Therapy should first be aimed at correcting those conditions which might produce a disturbance in the centers of coordination between the three nervous systems. Then the overtaxed nerve forces of the body as a whole should be relieved, the incoordination which has been a factor in the disease process should be eliminated, and the forces of the body should be coordinated. The diet should be corrected and sufficient stimulus of a medicinal nature should be added to keep the body in a normal force. Some cases that are psychological - where the body is amenable to suggestion - would benefit by suggestive therapy. Attention should be paid to attitudes of mind and to ideals.
# Related Chapters
- Mute
# External Links
- Muscle Tension Aphonia Video Example
Template:Skin and subcutaneous tissue symptoms and signs
Template:Nervous and musculoskeletal system symptoms and signs
Template:Urinary system symptoms and signs
Template:Cognition, perception, emotional state and behaviour symptoms and signs
Template:Speech and voice symptoms and signs
Template:General symptoms and signs | https://www.wikidoc.org/index.php/Abulia | |
a87d2e4354e6e9e8f45302df46a4f64bc2d5a5f8 | wikidoc | Acetone | Acetone
Acetone (also known as propanone, dimethyl ketone, 2-propanone, propan-2-one and β-ketopropane) is a colorless, mobile, flammable liquid. It is the simplest example of the ketones. Acetone is miscible with water, ethanol, ether, etc., and itself serves as an important solvent. The most familiar household use of acetone is as the active ingredient in nail polish remover and paint thinner. Acetone is also used to make plastic, fibers, drugs, and other chemicals. In addition to being manufactured as a chemical, acetone is also found naturally in the environment, including in small amounts in the human body.
# Production
Acetone is produced primarily in the cumene process. Previously, acetone was produced by the dry distillation of acetates, for example calcium acetate. During World War I a new process of producing acetone through bacterial fermentation was developed by Chaim Weizmann, later the first president of Israel, in order to help the British war effort. This Acetone Butanol Ethanol process was abandoned due to the small yield of Acetone Butanol compared to the organic waste.
# Biosynthesis
Small amounts of acetone are produced in the body by the decarboxylation of ketone bodies.
# Uses
## Cleaning fluid
Acetone is often the primary (or only) component in nail polish remover. Ethyl acetate, another organic solvent, is sometimes used as well. Acetone is also used as a superglue remover. It can be used for thinning and cleaning fiberglass resins and epoxies. It is a strong solvent for most plastics and synthetic fibres.
It is ideal for thinning fiberglass resin, cleaning fiberglass tools and dissolving two-part epoxies and superglue before hardening. A heavy-duty degreaser, it is useful in the preparation of metal prior to painting; it also thins polyester resins, vinyl and adhesives. It easily removes residues from glass and porcelain. In biological research contexts, buffers that contain acetone (such as citrate-buffered formalin) use the acetone to lyse cells for further experimentation.
Additionally, acetone is extremely effective when used as a cleaning agent when dealing with permanent markers.
## Solvent
Acetone can also dissolve many plastics, including those used in Nalgene bottles made of polystyrene, polycarbonate and some types of polypropylene.
In the laboratory, acetone is used as a polar aprotic solvent in a variety of organic reactions, such as SN2 reactions. The use of acetone solvent is also critical for the successful Jones oxidation. Technical grade acetone is inexpensive. Because of acetone's medium polarity, it dissolves a wide range of compounds. Thus, it is commonly loaded into squeeze bottles and used as a general solvent in rinsing laboratory glassware.
Acetone is also used extensively for the safe transporting and storing of acetylene. Vessels containing a porous material are first filled with acetone followed by acetylene, which dissolves into the acetone. One liter of acetone can dissolve around 250 liters of acetylene.
## Feedstock
An important industrial use for acetone involves its reaction with phenol for the manufacture of bisphenol A. Bisphenol A is an important component of many polymers such as polycarbonates, polyurethanes and epoxy resins. Acetone has also been used in the manufacture of cordite.
## Automotive fuel additive
Some automotive enthusiasts add acetone at around 1 part in 500 to their fuel, following claims of dramatic improvement in fuel economy and engine life. This practice is controversial as the body of systematic testing shows that acetone has no measurable effect or may in fact reduce engine life by adversely affecting fuel system parts. Debates on this subject and the perrenial claims of a "Big Oil" cover-up intensified when the practice was addressed on the popular American TV show MythBusters in 2006, and shown to have negative effect in the televised fuel economy test.. The jury is still out though, the only negatives to using acetone would be the result of exceeding the recommended blending calculation (one ounce of acetone to five gallons of gasoline). Even common paint thinner (which contains acetone, and other chemicals, some of which have been used to boost octane and fuel Formula One race cars, such as toluene and xylene) has been used as a gasoline and diesel fuel additive, point being that the chemical surface tension of the gasoline will be reduced to allow a more efficient combustion process to occur, thus resulting in better economy and performance. Conversely, alcohol based octane boosters, such as ethanol and methanol, actually increase the chemical surface tension of common gasoline, and this is precisely why less economy, less miles per gallon, occurs when using alcohol as an additive in gasoline.
## Other uses
Acetone is also used as a drying agent, due to the readiness with which it mixes with water, and its volatility.
It can be used as an artistic agent; when rubbed on the back of a laser print or photocopy placed face-down on another surface and burnished firmly, the toner of the image is allowed to transfer to the destination surface.
# Safety
## Acetone peroxide
When oxidized, acetone forms acetone peroxide as a by-product, which is a highly unstable compound. It may be formed accidentally, e.g. when waste hydrogen peroxide is poured into a carboy containing waste acetone solvent. Acetone peroxide is more than ten times as friction and shock sensitive as nitroglycerin. Due to its instability, it is rarely used, despite its easy chemical synthesis.
## Toxicology
Acetone is an irritant and inhalation may lead to hepatotoxic effects (causing liver damage). The vapors should be avoided. In no circumstance should it be consumed directly or indirectly. Always use goggles when handling acetone; it can cause permanent eye damage (corneal clouding).
Small amounts of acetone are metabolically produced in the body, mainly from fat. In humans, fasting significantly increases its endogenous production (see ketosis). Acetone can be elevated in diabetes. Contamination of water, food (e.g. milk), or the air (acetone is volatile) can lead to chronic exposure to acetone. A number of acute poisoning cases have been described. Relatively speaking, acetone is not a very toxic compound; it can, however, damage the mucosa of the mouth and can irritate and damage skin. Accidental intake of large amounts of acetone may lead to unconsciousness and death.
The effects of long-term exposure to acetone are known mostly from animal studies. Kidney, liver, and nerve damage, increased birth defects, and lowered reproduction ability of males (only) occurred in animals exposed long-term. It is not known if these same effects would be exhibited in humans. Pregnant women should avoid contact with acetone and acetone fumes in order to avoid the possibility of birth defects, including brain damage.
Interestingly, acetone has been shown to have anticonvulsant effects in animal models of epilepsy, in the absence of toxicity, when administered in millimolar concentrations. It has been hypothesized that the high fat low carbohydrate ketogenic diet used clinically to control drug-resistant epilepsy in children works by elevating acetone in the brain. | Acetone
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Template:Chembox new
Acetone (also known as propanone, dimethyl ketone, 2-propanone, propan-2-one and β-ketopropane) is a colorless, mobile, flammable liquid. It is the simplest example of the ketones. Acetone is miscible with water, ethanol, ether, etc., and itself serves as an important solvent. The most familiar household use of acetone is as the active ingredient in nail polish remover and paint thinner. Acetone is also used to make plastic, fibers, drugs, and other chemicals. In addition to being manufactured as a chemical, acetone is also found naturally in the environment, including in small amounts in the human body.
# Production
Acetone is produced primarily in the cumene process. Previously, acetone was produced by the dry distillation of acetates, for example calcium acetate. During World War I a new process of producing acetone through bacterial fermentation was developed by Chaim Weizmann, later the first president of Israel, in order to help the British war effort. This Acetone Butanol Ethanol process was abandoned due to the small yield of Acetone Butanol compared to the organic waste.
# Biosynthesis
Template:Seealso
Small amounts of acetone are produced in the body by the decarboxylation of ketone bodies.
# Uses
## Cleaning fluid
Acetone is often the primary (or only) component in nail polish remover. Ethyl acetate, another organic solvent, is sometimes used as well. Acetone is also used as a superglue remover. It can be used for thinning and cleaning fiberglass resins and epoxies. It is a strong solvent for most plastics and synthetic fibres.
It is ideal for thinning fiberglass resin, cleaning fiberglass tools and dissolving two-part epoxies and superglue before hardening. A heavy-duty degreaser, it is useful in the preparation of metal prior to painting; it also thins polyester resins, vinyl and adhesives. It easily removes residues from glass and porcelain. In biological research contexts, buffers that contain acetone (such as citrate-buffered formalin) use the acetone to lyse cells for further experimentation.
Additionally, acetone is extremely effective when used as a cleaning agent when dealing with permanent markers.
## Solvent
Acetone can also dissolve many plastics, including those used in Nalgene bottles made of polystyrene, polycarbonate and some types of polypropylene.[1]
In the laboratory, acetone is used as a polar aprotic solvent in a variety of organic reactions, such as SN2 reactions. The use of acetone solvent is also critical for the successful Jones oxidation. Technical grade acetone is inexpensive. Because of acetone's medium polarity, it dissolves a wide range of compounds. Thus, it is commonly loaded into squeeze bottles and used as a general solvent in rinsing laboratory glassware.
Acetone is also used extensively for the safe transporting and storing of acetylene. Vessels containing a porous material are first filled with acetone followed by acetylene, which dissolves into the acetone. One liter of acetone can dissolve around 250 liters of acetylene.
## Feedstock
An important industrial use for acetone involves its reaction with phenol for the manufacture of bisphenol A. Bisphenol A is an important component of many polymers such as polycarbonates, polyurethanes and epoxy resins. Acetone has also been used in the manufacture of cordite.
## Automotive fuel additive
Some automotive enthusiasts add acetone at around 1 part in 500 to their fuel, following claims of dramatic improvement in fuel economy and engine life.[2] This practice is controversial as the body of systematic testing shows that acetone has no measurable effect or may in fact reduce engine life by adversely affecting fuel system parts.[3][4][5] Debates on this subject and the perrenial claims of a "Big Oil" cover-up intensified when the practice was addressed on the popular American TV show MythBusters in 2006, and shown to have negative effect in the televised fuel economy test.[6]. The jury is still out though, the only negatives to using acetone would be the result of exceeding the recommended blending calculation (one ounce of acetone to five gallons of gasoline). Even common paint thinner (which contains acetone, and other chemicals, some of which have been used to boost octane and fuel Formula One race cars, such as toluene and xylene) has been used as a gasoline and diesel fuel additive, point being that the chemical surface tension of the gasoline will be reduced to allow a more efficient combustion process to occur, thus resulting in better economy and performance. Conversely, alcohol based octane boosters, such as ethanol and methanol, actually increase the chemical surface tension of common gasoline, and this is precisely why less economy, less miles per gallon, occurs when using alcohol as an additive in gasoline.
## Other uses
Acetone is also used as a drying agent, due to the readiness with which it mixes with water, and its volatility.
It can be used as an artistic agent; when rubbed on the back of a laser print or photocopy placed face-down on another surface and burnished firmly, the toner of the image is allowed to transfer to the destination surface.
# Safety
## Acetone peroxide
When oxidized, acetone forms acetone peroxide as a by-product, which is a highly unstable compound. It may be formed accidentally, e.g. when waste hydrogen peroxide is poured into a carboy containing waste acetone solvent. Acetone peroxide is more than ten times as friction and shock sensitive as nitroglycerin. Due to its instability, it is rarely used, despite its easy chemical synthesis.
## Toxicology
Acetone is an irritant and inhalation may lead to hepatotoxic effects (causing liver damage). The vapors should be avoided. In no circumstance should it be consumed directly or indirectly. Always use goggles when handling acetone; it can cause permanent eye damage (corneal clouding).
Small amounts of acetone are metabolically produced in the body, mainly from fat. In humans, fasting significantly increases its endogenous production (see ketosis). Acetone can be elevated in diabetes. Contamination of water, food (e.g. milk), or the air (acetone is volatile) can lead to chronic exposure to acetone. A number of acute poisoning cases have been described. Relatively speaking, acetone is not a very toxic compound; it can, however, damage the mucosa of the mouth and can irritate and damage skin. Accidental intake of large amounts of acetone may lead to unconsciousness and death.
The effects of long-term exposure to acetone are known mostly from animal studies. Kidney, liver, and nerve damage, increased birth defects, and lowered reproduction ability of males (only) occurred in animals exposed long-term. It is not known if these same effects would be exhibited in humans. Pregnant women should avoid contact with acetone and acetone fumes in order to avoid the possibility of birth defects, including brain damage.
Interestingly, acetone has been shown to have anticonvulsant effects in animal models of epilepsy, in the absence of toxicity, when administered in millimolar concentrations.[7] It has been hypothesized that the high fat low carbohydrate ketogenic diet used clinically to control drug-resistant epilepsy in children works by elevating acetone in the brain.[7] | https://www.wikidoc.org/index.php/Acetone | |
86fdcf96db18201a3f498190ab2a7ac045fbea68 | wikidoc | Achiote | Achiote
Achiote (Bixa orellana) is a shrub or small tree from the tropical region of the American continent. The name derives from the Nahuatl word for the shrub, achiotl. It is also known as Aploppas, and its original Tupi name urucu. It is cultivated there and in Southeast Asia, where it was introduced by the Spanish in the 17th century. It is best known as the source of the natural pigment annatto, produced from the fruit. The plant bears pink flowers and bright red spiny fruits which contain red seeds. The fruits dry and harden to brown capsules.
The inedible fruit is harvested for its seeds, which contain annatto, also called bixin. It can be extracted by stirring the seeds in water. It is used to color food products, such as cheeses, fish, and salad oil. It is a main ingredient in the Mexican spice mixture recado rojo, or "achiote paste". The seeds are ground and used as a nearly flavorless but colorful additive in Latin American, Jamaican and Filipino cuisine. Annatto is growing in popularity as a natural alternative to synthetic food coloring compounds.
# Ethnomedical uses
- The achiote has long been used by American Indians to make body paint, especially for the lips, which is the origin of the plant's nickname, lipstick tree.
- Parts of the plant can be used to make medicinal remedies for such conditions as sunstroke, tonsilitis, burns, leprosy, pleurisy, apnoea, rectal discomfort, and headaches.
- The sap from fruits is also used to treat type II diabetes, and fungal infections.
- fruiting branch showing seed pod
fruiting branch showing seed pod
- File:Bixa orellana.jpg
- Half of a seed pod showing seeds inside
Half of a seed pod showing seeds inside | Achiote
Achiote (Bixa orellana) is a shrub or small tree from the tropical region of the American continent. The name derives from the Nahuatl word for the shrub, achiotl. It is also known as Aploppas, and its original Tupi name urucu. It is cultivated there and in Southeast Asia, where it was introduced by the Spanish in the 17th century. It is best known as the source of the natural pigment annatto, produced from the fruit. The plant bears pink flowers and bright red spiny fruits which contain red seeds. The fruits dry and harden to brown capsules.
The inedible fruit is harvested for its seeds, which contain annatto, also called bixin. It can be extracted by stirring the seeds in water. It is used to color food products, such as cheeses, fish, and salad oil. It is a main ingredient in the Mexican spice mixture recado rojo, or "achiote paste". The seeds are ground and used as a nearly flavorless but colorful additive in Latin American, Jamaican and Filipino cuisine. Annatto is growing in popularity as a natural alternative to synthetic food coloring compounds.
# Ethnomedical uses
- The achiote has long been used by American Indians to make body paint, especially for the lips, which is the origin of the plant's nickname, lipstick tree.
- Parts of the plant can be used to make medicinal remedies for such conditions as sunstroke, tonsilitis, burns, leprosy, pleurisy, apnoea, rectal discomfort, and headaches.
- The sap from fruits is also used to treat type II diabetes, and fungal infections.
- fruiting branch showing seed pod
fruiting branch showing seed pod
- File:Bixa orellana.jpg
- Half of a seed pod showing seeds inside
Half of a seed pod showing seeds inside | https://www.wikidoc.org/index.php/Achiote | |
7bbc47e3452aaeea05ef61d5a2c107fedf44f2f0 | wikidoc | Rosacea | Rosacea
# Overview
Rosacea (Template:IPAEng) is a common but often misunderstood condition that is estimated to affect over 45 million people worldwide. It affects white-skinned people of mostly north-western European descent, and has been nicknamed the 'curse of the Celts' by some in Ireland. It begins as erythema (flushing and redness) on the central face and across the cheeks, nose, or forehead but can also less commonly affect the neck and chest. As rosacea progresses, other symptoms can develop such as semi-permanent erythema, telangiectasia (dilation of superficial blood vessels on the face), red domed papules (small bumps) and pustules, red gritty eyes, burning and stinging sensations, and in some advanced cases, a red lobulated nose (rhinophyma). The disorder can be confused and co-exist with acne vulgaris and/or seborrheic dermatitis. Rosacea affects both sexes, but is almost three times more common in women, and has a peak age of onset between 30 and 60. The presence of rash on the scalp or ears suggests a different or co-existing diagnosis, as rosacea is primarily a facial diagnosis.
# Subtypes and symptoms
There are four identified rosacea subtypes and patients may have more than one subtype present.
- Erythematotelangiectatic rosacea: Permanent redness (erythema) with a tendency to flush and blush easily. It is also common to have small blood vessels visible near the surface of the skin (telangiectasias) and possibly burning or itching sensations.
- Papulopustular rosacea: Some permanent redness with red bumps (papules) with some pus filled (pustules) (which typically last 1-4 days); this subtype can be easily confused with acne.
- Phymatous rosacea: This subtype is most commonly associated with rhinophyma, an enlargement of the nose. Symptoms include thickening skin, irregular surface nodularities, and enlargement. Phymatous rosacea can also affect the chin (gnatophyma), forehead (metophyma), cheeks, eyelids (blepharophyma), and ears (otophyma). Small blood vessels visible near the surface of the skin (telangiectasias) may be present.
- Ocular rosacea: Red, dry and irritated eyes and eyelids. Some other symptoms include foreign body sensations, itching and burning.
- Opthalmic rosacea. Adapted from Dermatology Atlas.
- Opthalmic rosacea. Adapted from Dermatology Atlas.
- Opthalmic rosacea. Adapted from Dermatology Atlas.
There have been other descriptive terms applied to presentations of rosacea, but these are not formally accepted as subtyes of rosacea:
- Granulomatous rosacea.
- The rare and severely scarring Rosacea fulminans (pyoderma faciale) occurring exclusively in women after adolescence and most commonly in their early 20s,
- Perioral dermatitis, which is better described as periorificial dermatitis, but similarly treated with topical metronidazole.
- Persistent edema of rosacea.
- Rosacea Conglobata.
- Persisting redness and oedema of the upper half of the face has been termed Morbihan disease.
Rosacea sufferers often report periods of depression stemming from cosmetic disfigurement, painful burning sensations, and decreases in quality of life.
# Causes
Richard L. Gallo and colleagues recently noticed that patients with rosacea had elevated levels of the peptide cathelicidin and elevated levels of stratum corneum tryptic enzymes (SCTEs). Antibiotics have been used in the past to treat rosacea, but antibiotics may only work because they inhibit some SCTEs. See the August 5, 2007 issue of Nature Medicine for details.
Rosacea has a hereditary component and those that are fair-skinned of European or Celtic ancestry have a higher genetic predisposition to developing it. Women are more commonly affected but when men develop rosacea it tends to be more severe. People of all ages can get rosacea but there is a higher instance in the 30-50 age group. The first signs of rosacea are said to be persisting redness due to exercise, changes in temperature, and cleansing.
Triggers that cause episodes of flushing and blushing play a part in the development of rosacea. Exposure to temperature extremes can cause the face to become flushed as well as strenuous exercise, heat from sunlight, severe sunburn, stress, anxiety, cold wind, moving to a warm or hot environment from a cold one such as heated shops and offices during the winter. There are also some foods and drinks that can trigger flushing, these include alcohol, foods and beverages containing caffeine (especially, hot tea and coffee), foods high in histamines and spicy food, as well as fruits containing high levels of antioxidants, such as red grapes.
Certain medications and topical irritants can quickly progress rosacea. If redness persists after using a treatment then it should be stopped immediately. Some acne and wrinkle treatments that have been reported to cause rosacea include microdermabrasion, chemical peels, high dosages of isotretinoin, benzoyl peroxide and tretinoin. Steroid induced rosacea is the term given to rosacea caused by the use of topical or nasal steroids. These steroids are often prescribed for seborrheic dermatitis. Dosage should be slowly decreased and not immediately stopped to avoid a flare up.
Studies of rosacea and demodex mites have revealed that some people with rosacea have increased numbers of the mite, especially those with steroid induced rosacea. When large numbers are present they may play a role along with other triggers. On other occasions Demodicidosis (Mange) is a separate condition that may have "rosacea-like" appearances.
It has also been suggested that rosacea might be a neurological disorder resulting from hypersensitization of sensory neurons following activation of the plasma kallikrein-kinin system by exposure to intestinal bacteria in the digestive tract.
# Physical Examination
## Gallery
- Acne rosacea. Adapted from [
- Acne rosacea. Adapted from [
- Acne rosacea. Adapted from [
- Acne rosacea. Adapted from [
- Acne rosacea. Adapted from [
- Acne rosacea. Adapted from [
- Acne rosacea. Adapted from [
- Acne rosacea. Adapted from [
- Acne rosacea. Adapted from [
- Acne rosacea. Adapted from [
- Acne rosacea. Adapted from [
- Acne rosacea. Adapted from [
- Acne rosacea.Adapted from [
- Acne rosacea. Adapted from [
# Treatments
Treating rosacea varies from patient to patient depending on severity and subtypes. Dermatologists are recommended to take a subtype-directed approach to treating rosacea patients.
Trigger avoidance can help reduce the onset of rosacea but alone will not normally cause remission for all but mild cases. The National Rosacea Society recommends that a diary be kept to help identify and reduce triggers.
It is important to have a gentle skin cleansing regimen using non-irritating cleansers. Protection from the sun is important and daily use of a sunscreen of at least SPF 15 containing a physical blocker such as zinc oxide or titanium dioxide is advised although chemical sunscreens, if non-irritating to the skin, are also an option.
Oral tetracycline antibiotics (tetracycline, doxycycline, minocycline) and topical antibiotics such as metronidazole are usually the first line of defense prescribed by doctors to relieve papules, pustules, inflammation and some redness. Topical Azelaic acid such as Finacea maya help reduce inflammation. Oral antibiotics may help to relieve symptoms of ocular rosacea. If papules and pustules persist, then sometimes isotretinoin can be prescribed. Isotretinoin has many side effects and is normally used to treat severe acne but in low dosages is proven to be effective against papulopustular and phymatous rosacea.
The treatment of flushing and blushing has been attempted by means of the centrally acting α-2 agonist clonidine, but there is no evidence whatsoever that this is of any benefit. The same is true of the beta-blockers nadolol and propanolol. If flushing occurs with red wine consumption, then complete avoidance helps. There is no evidence at all that antihistamines are of any benefit in rosacea.
People who develop infections of the eyelids must practice frequent eyelid hygiene. Daily scrubbing the eyelids gently with diluted baby shampoo or an over-the-counter eyelid cleaner and applying warm (but not hot) compresses several times a day is recommended.
Dermatological vascular laser (single wavelength) or Intense Pulsed Light (broad spectrum) machines offer one of the best treatments for rosacea, in particular the erythema (redness) of the skin. They use light to penetrate the epidermis to target the capillaries in the dermis layer of the skin. The light is absorbed by oxy-hemoglobin which heat up causing the capillary walls to heat up to 70ºC, damaging them, causing them to be absorbed by the body's natural defence mechanism.
CO2 lasers can be used to remove excess tissue caused by phymatous rosacea. CO2 lasers emit a wavelength that is absorbed directly by the skin. The laser beam can be focused into a thin beam and used as a scalpel or defocused and used to vaporise tissue. Low level light therapies have also been used to treat rosacea.
One alternative skin treatment, fashionable in the Victorian and Edwardian eras, was Sulphur. Recently Sulphur has re-gained some credibility as a safe alternative to steroids and coal tar.
## Antibiotic Regimen
- Acne rosacea
- 1. Facial erythema
- Preferred regimen: Brimonidine gel Topical bid, applied to the affected area
- 2. Papulopustular rosacea
- Preferred regimen (1): Azelaic acid gel Topical bid
- Preferred regimen (2): Metronidazole cream Topical qd
# Famous people
Famous people with Rosacea include:
- Bill Clinton.
- J. P. Morgan
- Diana, Princess of Wales
- W. C. Fields
- Alex Ferguson
- Rosie O'Donnell
- Mariah Carey
- Margaret Bobonich
- Ricky Wilson
- Lisa Faulkner
- Davina Wong
- Rembrandt | Rosacea
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]
# Overview
Rosacea (Template:IPAEng) is a common but often misunderstood condition that is estimated to affect over 45 million people worldwide. It affects white-skinned people of mostly north-western European descent, and has been nicknamed the 'curse of the Celts' by some in Ireland. It begins as erythema (flushing and redness) on the central face and across the cheeks, nose, or forehead but can also less commonly affect the neck and chest. As rosacea progresses, other symptoms can develop such as semi-permanent erythema, telangiectasia (dilation of superficial blood vessels on the face), red domed papules (small bumps) and pustules, red gritty eyes, burning and stinging sensations, and in some advanced cases, a red lobulated nose (rhinophyma). The disorder can be confused and co-exist with acne vulgaris and/or seborrheic dermatitis. Rosacea affects both sexes, but is almost three times more common in women, and has a peak age of onset between 30 and 60. The presence of rash on the scalp or ears suggests a different or co-existing diagnosis, as rosacea is primarily a facial diagnosis.
# Subtypes and symptoms
There are four identified rosacea subtypes[1] and patients may have more than one subtype present.
- Erythematotelangiectatic rosacea: Permanent redness (erythema) with a tendency to flush and blush easily. It is also common to have small blood vessels visible near the surface of the skin (telangiectasias) and possibly burning or itching sensations.
- Papulopustular rosacea: Some permanent redness with red bumps (papules) with some pus filled (pustules) (which typically last 1-4 days); this subtype can be easily confused with acne.
- Phymatous rosacea: This subtype is most commonly associated with rhinophyma, an enlargement of the nose. Symptoms include thickening skin, irregular surface nodularities, and enlargement. Phymatous rosacea can also affect the chin (gnatophyma), forehead (metophyma), cheeks, eyelids (blepharophyma), and ears (otophyma).[2] Small blood vessels visible near the surface of the skin (telangiectasias) may be present.
- Ocular rosacea: Red, dry and irritated eyes and eyelids. Some other symptoms include foreign body sensations, itching and burning.
- Opthalmic rosacea. Adapted from Dermatology Atlas.[3]
- Opthalmic rosacea. Adapted from Dermatology Atlas.[3]
- Opthalmic rosacea. Adapted from Dermatology Atlas.[3]
There have been other descriptive terms applied to presentations of rosacea, but these are not formally accepted as subtyes of rosacea:[4]
- Granulomatous rosacea.[5]
- The rare and severely scarring Rosacea fulminans (pyoderma faciale) occurring exclusively in women after adolescence and most commonly in their early 20s,[6][7]
- Perioral dermatitis, which is better described as periorificial dermatitis, but similarly treated with topical metronidazole.[8]
- Persistent edema of rosacea.[citation needed]
- Rosacea Conglobata.[citation needed]
- Persisting redness and oedema of the upper half of the face has been termed Morbihan disease.[9][10]
Rosacea sufferers often report periods of depression stemming from cosmetic disfigurement, painful burning sensations, and decreases in quality of life.[11]
# Causes
Richard L. Gallo and colleagues recently noticed that patients with rosacea had elevated levels of the peptide cathelicidin and elevated levels of stratum corneum tryptic enzymes (SCTEs). Antibiotics have been used in the past to treat rosacea, but antibiotics may only work because they inhibit some SCTEs. See the August 5, 2007 issue of Nature Medicine for details.
Rosacea has a hereditary component and those that are fair-skinned of European or Celtic ancestry have a higher genetic predisposition to developing it. Women are more commonly affected but when men develop rosacea it tends to be more severe. People of all ages can get rosacea but there is a higher instance in the 30-50 age group. The first signs of rosacea are said to be persisting redness due to exercise, changes in temperature, and cleansing.
Triggers that cause episodes of flushing and blushing play a part in the development of rosacea. Exposure to temperature extremes can cause the face to become flushed as well as strenuous exercise, heat from sunlight, severe sunburn, stress, anxiety, cold wind, moving to a warm or hot environment from a cold one such as heated shops and offices during the winter. There are also some foods and drinks that can trigger flushing, these include alcohol, foods and beverages containing caffeine (especially, hot tea and coffee), foods high in histamines and spicy food, as well as fruits containing high levels of antioxidants, such as red grapes.
Certain medications and topical irritants can quickly progress rosacea. If redness persists after using a treatment then it should be stopped immediately. Some acne and wrinkle treatments that have been reported to cause rosacea include microdermabrasion, chemical peels, high dosages of isotretinoin, benzoyl peroxide and tretinoin. Steroid induced rosacea is the term given to rosacea caused by the use of topical or nasal steroids. These steroids are often prescribed for seborrheic dermatitis. Dosage should be slowly decreased and not immediately stopped to avoid a flare up.
Studies of rosacea and demodex mites have revealed that some people with rosacea have increased numbers of the mite, especially those with steroid induced rosacea.[12] When large numbers are present they may play a role along with other triggers. On other occasions Demodicidosis (Mange) is a separate condition that may have "rosacea-like" appearances.[13]
It has also been suggested that rosacea might be a neurological disorder resulting from hypersensitization of sensory neurons following activation of the plasma kallikrein-kinin system by exposure to intestinal bacteria in the digestive tract.[14]
# Physical Examination
## Gallery
- Acne rosacea. Adapted from [http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=6
- Acne rosacea. Adapted from [http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=6
- Acne rosacea. Adapted from [http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=6
- Acne rosacea. Adapted from [http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=6
- Acne rosacea. Adapted from [http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=6
- Acne rosacea. Adapted from [http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=6
- Acne rosacea. Adapted from [http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=6
- Acne rosacea. Adapted from [http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=6
- Acne rosacea. Adapted from [http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=6
- Acne rosacea. Adapted from [http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=6
- Acne rosacea. Adapted from [http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=6
- Acne rosacea. Adapted from [http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=6
- Acne rosacea.Adapted from [http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=6
- Acne rosacea. Adapted from [http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=6
# Treatments
Treating rosacea varies from patient to patient depending on severity and subtypes. Dermatologists are recommended to take a subtype-directed approach to treating rosacea patients.[15]
Trigger avoidance can help reduce the onset of rosacea but alone will not normally cause remission for all but mild cases. The National Rosacea Society recommends that a diary be kept to help identify and reduce triggers.
It is important to have a gentle skin cleansing regimen using non-irritating cleansers. Protection from the sun is important and daily use of a sunscreen of at least SPF 15 containing a physical blocker such as zinc oxide or titanium dioxide is advised although chemical sunscreens, if non-irritating to the skin, are also an option.
Oral tetracycline antibiotics (tetracycline, doxycycline, minocycline) and topical antibiotics such as metronidazole are usually the first line of defense prescribed by doctors to relieve papules, pustules, inflammation and some redness.[16] Topical Azelaic acid such as Finacea maya help reduce inflammation. Oral antibiotics may help to relieve symptoms of ocular rosacea. If papules and pustules persist, then sometimes isotretinoin can be prescribed.[17] Isotretinoin has many side effects and is normally used to treat severe acne but in low dosages is proven to be effective against papulopustular and phymatous rosacea.
The treatment of flushing and blushing has been attempted by means of the centrally acting α-2 agonist clonidine, but there is no evidence whatsoever that this is of any benefit. The same is true of the beta-blockers nadolol and propanolol. If flushing occurs with red wine consumption, then complete avoidance helps. There is no evidence at all that antihistamines are of any benefit in rosacea.
People who develop infections of the eyelids must practice frequent eyelid hygiene. Daily scrubbing the eyelids gently with diluted baby shampoo or an over-the-counter eyelid cleaner and applying warm (but not hot) compresses several times a day is recommended.
Dermatological vascular laser (single wavelength) or Intense Pulsed Light (broad spectrum) machines offer one of the best treatments for rosacea, in particular the erythema (redness) of the skin.[18] They use light to penetrate the epidermis to target the capillaries in the dermis layer of the skin. The light is absorbed by oxy-hemoglobin which heat up causing the capillary walls to heat up to 70ºC, damaging them, causing them to be absorbed by the body's natural defence mechanism.
CO2 lasers can be used to remove excess tissue caused by phymatous rosacea. CO2 lasers emit a wavelength that is absorbed directly by the skin. The laser beam can be focused into a thin beam and used as a scalpel or defocused and used to vaporise tissue. Low level light therapies have also been used to treat rosacea.
One alternative skin treatment, fashionable in the Victorian and Edwardian eras, was Sulphur. Recently Sulphur has re-gained some credibility as a safe alternative to steroids and coal tar.
## Antibiotic Regimen
- Acne rosacea [19]
- 1. Facial erythema
- Preferred regimen: Brimonidine gel Topical bid, applied to the affected area
- 2. Papulopustular rosacea
- Preferred regimen (1): Azelaic acid gel Topical bid
- Preferred regimen (2): Metronidazole cream Topical qd
# Famous people
Famous people with Rosacea include:
- Bill Clinton.[20]
- J. P. Morgan
- Diana, Princess of Wales[21]
- W. C. Fields
- Alex Ferguson
- Rosie O'Donnell[22]
- Mariah Carey[23]
- Margaret Bobonich[24]
- Ricky Wilson[25]
- Lisa Faulkner[26]
- Davina Wong
- Rembrandt[27] | https://www.wikidoc.org/index.php/Acne_rosacea | |
9289b4443e2d909efb339e08fc03f73a3cf2e9c8 | wikidoc | Actinic | Actinic
Actinic keratosis (also called solar keratosis, or AK) is a premalignant condition of thick, scaly, or crusty patches of skin. It is most common in fair-skinned people who are frequently exposed to the sun, because their pigment isn't very protective. It usually is accompanied by solar damage. Since some of these pre-cancers progress to squamous cell carcinoma, they should be treated.
When skin is exposed to the sun constantly, thick, scaly, or crusty bumps appear. The scaly or crusty part of the bump is dry and rough. The growths start out as flat scaly areas, and later grow into a tough, wart-like area.
An actinic keratosis site commonly ranges between 2 and 6 millimeters in size, and can be dark or light, tan, pink, red, a combination of all these, or have the same pigment as the surrounding skin. It may appear on any sun-exposed area, such as the face, ears, neck, scalp, chest, backs of hands, forearms, or lips.
# Prevention
Preventive measures recommended for AK are similar to those for skin cancer:
- Not staying in the sun for long periods of time without protection (e.g.:sunscreen, clothing, hats).
- Frequently applying powerful sunscreens with SPF ratings greater than 15 and that also block both UVA and UVB light.
- Using sunscreen even in winter sun exposure.
- Wearing sun protective clothing such as hats, long-sleeved shirts, long skirts, or pants.
- Avoiding sun exposure during noon hours is very helpful because ultraviolet light is the most powerful at that time.
# Diagnosis
Doctors can usually identify AK by doing a thorough examination. A biopsy may be necessary when the keratosis is large and/or thick, to make sure that the bump is a keratosis and not a skin cancer. Seborrheic keratoses are other bumps that appear in groups like the actinic keratosis but are not caused by sun exposure, and are not related to skin cancers. Seborrheic keratoses may be mistaken for an actinic keratosis.
# Treatment
Various modalities are employed in the treatment of actinic keratosis:
- Cryosurgery, e.g. with liquid nitrogen, by "freezing off" the AKs.
- 5-fluorouracil (a chemotherapy agent): a cream that contains this medication causes AKs to become red and inflamed before they fall off.
- Photodynamic therapy: this new therapy involves injecting a chemical into the bloodstream, which makes AKs more sensitive to any form of light.
- Laser , notably CO2 and Er:YAG lasers. A Laser resurfacing technique is often used with diffuse AKs.
- Electrocautery: burning off AKs with electricity.
- Immunotherapy: topical treatment with imiquimod (Aldara), an immune enhancing agent
- Different forms of surgery.
- Crocodile oil: is available as a skin balm and has been used successfully as is a natural remedy.
Regular follow-up after treatment is advised by many doctors. The regular checks are to make sure new bumps have not developed and that old ones haven't become thicker and/or have skin disease.
# Experimental treatments
In 2007, Australia biopharmaceutical company Clinuvel Pharmaceuticals Limited began clinical trials with a melanocyte-stimulating hormone called melanotan which they refer to with the proprietary name CUV1647 for actinic keratosis in organ transplant patients.
Another Australian biopharmaceutical company Peplin is also developing a topical treatment for actinic keratosis. Formed in 1998 they are currently developing PEP005, which is the first in a new class of compounds and which is derived from Euphorbia peplus, or E. peplus, a rapidly growing, readily-available plant, commonly referred to as petty spurge or radium weed. The sap of E. peplus has a long history of traditional use for a variety of conditions, including the topical self-treatment of various skin disorders, such as skin cancer and pre-cancerous skin lesions. The company has recently redomiciled to the USA and is about to enter phase III trials with PEP005. | Actinic
Template:DiseaseDisorder infobox
Actinic keratosis (also called solar keratosis, or AK) is a premalignant condition of thick, scaly, or crusty patches of skin. It is most common in fair-skinned people who are frequently exposed to the sun, because their pigment isn't very protective. It usually is accompanied by solar damage. Since some of these pre-cancers progress to squamous cell carcinoma, they should be treated.
When skin is exposed to the sun constantly, thick, scaly, or crusty bumps appear. The scaly or crusty part of the bump is dry and rough. The growths start out as flat scaly areas, and later grow into a tough, wart-like area.
An actinic keratosis site commonly ranges between 2 and 6 millimeters in size, and can be dark or light, tan, pink, red, a combination of all these, or have the same pigment as the surrounding skin. It may appear on any sun-exposed area, such as the face, ears, neck, scalp, chest, backs of hands, forearms, or lips.
# Prevention
Preventive measures recommended for AK are similar to those for skin cancer:
- Not staying in the sun for long periods of time without protection (e.g.:sunscreen, clothing, hats).
- Frequently applying powerful sunscreens with SPF ratings greater than 15 and that also block both UVA and UVB light.
- Using sunscreen even in winter sun exposure.
- Wearing sun protective clothing such as hats, long-sleeved shirts, long skirts, or pants.
- Avoiding sun exposure during noon hours is very helpful because ultraviolet light is the most powerful at that time.
# Diagnosis
Doctors can usually identify AK by doing a thorough examination. A biopsy may be necessary when the keratosis is large and/or thick, to make sure that the bump is a keratosis and not a skin cancer. Seborrheic keratoses are other bumps that appear in groups like the actinic keratosis but are not caused by sun exposure, and are not related to skin cancers. Seborrheic keratoses may be mistaken for an actinic keratosis.
# Treatment
Various modalities are employed in the treatment of actinic keratosis:
- Cryosurgery, e.g. with liquid nitrogen, by "freezing off" the AKs.
- 5-fluorouracil (a chemotherapy agent): a cream that contains this medication causes AKs to become red and inflamed before they fall off.
- Photodynamic therapy: this new therapy involves injecting a chemical into the bloodstream, which makes AKs more sensitive to any form of light.
- Laser , notably CO2 and Er:YAG lasers. A Laser resurfacing technique is often used with diffuse AKs.
- Electrocautery: burning off AKs with electricity.
- Immunotherapy: topical treatment with imiquimod (Aldara), an immune enhancing agent
- Different forms of surgery.
- Crocodile oil: is available as a skin balm and has been used successfully as is a natural remedy.
Regular follow-up after treatment is advised by many doctors. The regular checks are to make sure new bumps have not developed and that old ones haven't become thicker and/or have skin disease.
# Experimental treatments
In 2007, Australia biopharmaceutical company Clinuvel Pharmaceuticals Limited began clinical trials with a melanocyte-stimulating hormone called melanotan which they refer to with the proprietary name CUV1647 for actinic keratosis in organ transplant patients.[1][2]
Another Australian biopharmaceutical company Peplin [3] is also developing a topical treatment for actinic keratosis. Formed in 1998 they are currently developing PEP005, which is the first in a new class of compounds and which is derived from Euphorbia peplus, or E. peplus, a rapidly growing, readily-available plant, commonly referred to as petty spurge or radium weed. The sap of E. peplus has a long history of traditional use for a variety of conditions, including the topical self-treatment of various skin disorders, such as skin cancer and pre-cancerous skin lesions. The company has recently redomiciled to the USA and is about to enter phase III trials with PEP005.
# External links
- American Academy of Dermatology
- American Osteopathic College of Dermatology
- National Library of Medicine and the National Institute of Health
- Actinic Keratosis photo library at Dermnet
- Medicinenet's article on Actinic Keratosis
- Information on Actinic Keratosis from The Skin Cancer Foundation | https://www.wikidoc.org/index.php/Actinic | |
d20e49f58e5bab02d12ac9085c7fae0e7fc7e615 | wikidoc | Activin | Activin
# Overview
Activin is a peptide that enhances FSH synthesis and secretion and participates in the regulation of the menstrual cycle. It does the opposite as inhibin. Many other functions have been found to be exerted by activin, including their roles in cell proliferation, differentiation, apoptosis, metabolism, homeostasis, immune response, wound repair, and endocrine function
Like inhibin (and AMH) activin belongs to TGF-β superfamily.
# Structure
Activin contains two beta subunit that are identical to the two beta subunits (A or B) of inhibin, allowing for the formation of three forms of activin: A, AB, and B.
They are linked by a single covalent disulfide bond.
# Function
Activin is produced in the gonads, pituitary gland, placenta and other organs:
- In the ovarian follicle, activin increases FSH binding and FSH induced aromatization. It participates in androgen synthesis enhancing LH action in the ovary and testis. In the male, activin enhances spermatogenesis.
- Activin is strongly expressed in wounded skin, and overexpression of activin in epidermis of transgenic mice improves wound healing and enhances scar formation. Its action in wound repair and skin morphogenesis is through stimulation of keratinocytes and stromal cells in a dose-dependent manner.
- Activin also regulates the morphogenesis of branching organs such as the prostate, lung, and especially kidney. Activin A increased the expression level of type I collagen suggesting that activtin A acts as a potent activator of fibroblasts.
# Mechanism
As with other members of the superfamily, activins interact with two types of cell surface transmembrane receptors (Types I and II) which have intrinsic serine/threonine kinase activities in their cytoplasmic domains.
Activin binds to the Type II receptor and initiates a cascade reaction that leads to the recruitment, phosphorylation, and activation of Type I activin receptor. This then interacts with and then phosphorylates Smad2 and Smad3, two of the cytoplasmic Smad proteins.
Smad3 then translocates to the nucleus and interacts with Smad4 through multimerization, resulting in their modulation as transcription factor complexes responsible for the expression of a large variety of genes. | Activin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753
# Overview
Activin is a peptide that enhances FSH synthesis and secretion and participates in the regulation of the menstrual cycle. It does the opposite as inhibin. Many other functions have been found to be exerted by activin, including their roles in cell proliferation, differentiation, apoptosis[1], metabolism, homeostasis, immune response, wound repair[2], and endocrine function
Like inhibin (and AMH) activin belongs to TGF-β superfamily.
# Structure
Activin contains two beta subunit that are identical to the two beta subunits (A or B) of inhibin, allowing for the formation of three forms of activin: A, AB, and B.
They are linked by a single covalent disulfide bond.
# Function
Activin is produced in the gonads, pituitary gland, placenta and other organs:
- In the ovarian follicle, activin increases FSH binding and FSH induced aromatization. It participates in androgen synthesis enhancing LH action in the ovary and testis. In the male, activin enhances spermatogenesis.
- Activin is strongly expressed in wounded skin, and overexpression of activin in epidermis of transgenic mice improves wound healing and enhances scar formation. Its action in wound repair and skin morphogenesis is through stimulation of keratinocytes and stromal cells in a dose-dependent manner.[3]
- Activin also regulates the morphogenesis of branching organs such as the prostate, lung, and especially kidney. Activin A increased the expression level of type I collagen suggesting that activtin A acts as a potent activator of fibroblasts.
# Mechanism
As with other members of the superfamily, activins interact with two types of cell surface transmembrane receptors (Types I and II) which have intrinsic serine/threonine kinase activities in their cytoplasmic domains.
Activin binds to the Type II receptor and initiates a cascade reaction that leads to the recruitment, phosphorylation, and activation of Type I activin receptor. This then interacts with and then phosphorylates Smad2 and Smad3, two of the cytoplasmic Smad proteins.
Smad3 then translocates to the nucleus and interacts with Smad4 through multimerization, resulting in their modulation as transcription factor complexes responsible for the expression of a large variety of genes. | https://www.wikidoc.org/index.php/Activin | |
46520656ba6fed085e43b7610d2b9c18a959a418 | wikidoc | Naphtha | Naphtha
# Overview
Naphtha (/ˈnæfθə/ or /ˈnæpθə/) normally refers to a number of flammable liquid mixtures of hydrocarbons, i.e., a component of natural gas condensate or a distillation product from petroleum, coal tar or peat boiling in a certain range and containing certain hydrocarbons. It is a broad term covering among the lightest and most volatile fractions of the liquid hydrocarbons in petroleum. Naphtha is a colorless to reddish-brown volatile aromatic liquid, very similar to gasoline.
In petroleum engineering, full range naphtha is defined as the fraction of hydrocarbons in petroleum boiling between 30 °C and 200 °C. It consists of a complex mixture of hydrocarbon molecules generally having between 5 and 12 carbon atoms. It typically constitutes 15–30% of crude oil, by weight. Light naphtha is the fraction boiling between 30 °C and 90 °C and consists of molecules with 5–6 carbon atoms. Heavy naphtha boils between 90 °C and 200 °C and consists of molecules with 6–12 carbons.
Naphtha is used primarily as feedstock for producing high octane gasoline (via the catalytic reforming process). It is also used in the bitumen mining industry as a diluent, the petrochemical industry for producing olefins in steam crackers, and the chemical industry for solvent (cleaning) applications. Common products made with it include lighter fluid, fuel for camp stoves, and some cleaning solvents.
# Etymology
The word naphtha came from Latin and Greek where it derived from Persian. In Ancient Greek, it was used to refer to any sort of petroleum or pitch. It appears in Arabic as "nafţ" (نَفْط) ("petroleum"), and in Hebrew as "neft" (נֵפְט). Arabs and Persians have used and distilled petroleum for tar and fuel from ancient times, as attested in local Greek and Roman histories of the region.
The second book of the Maccabees in the Septuagint, part of the Old Testament canon in some Christian denominations, uses the word "naphtha" to refer to a miraculous flammable liquid. This account says that Nehemiah and the levitical priests associated with him called the liquid "nephthar," meaning "purification," but "most people" call it naphtha(or Nephi).
Naphtha is the root of the word naphthalene. The second syllable of "naphtha" can also be recognised in phthalate.
It also enters the word napalm from "naphthenic acid and palmitic acid", as the first napalm was made from a mixture of naphthenic acid with aluminium and magnesium salts of palmitic acid.
In older usage, "naphtha" simply meant crude oil, but this usage is now obsolete in English.
The Ukrainian and Belarusian word нафта (lit. nafta), the Russian word нефть (lit. neft') and the Persian naft ( نفت) mean "crude oil". Also, in Italy, Czech Republic, Serbia, Bosnia-Herzegovina, Croatia, Slovenia nafta (нафта in Serbian Cyrillic transcription) is colloquially used to indicate diesel fuel and crude oil. In Slovakia, nafta was historically used for both diesel fuel and crude oil, but its use for crude oil is now obsolete and it generally indicates diesel fuel (crude oil is referred to as ropa). In Bulgarian, nafta means diesel fuel, while neft means crude oil. "Nafta" is also used in Argentina and Uruguay to refer to gasoline. In Poland, the "birthplace" of petroleum industry, word "nafta" means kerosene
There is a conjecture that the Greek word naphtha came from the Indo-Iranian god name Apam Napat, which occurs in Vedic and in Avestic.
# Health and safety considerations
Forms of naphtha may be carcinogenic, and frequently products sold as naphtha contain some impurities which may also have harmful properties of their own.
Like many hydrocarbon products, they are products of a refining process in which a complex soup of chemicals is broken into another range of chemicals, which are then graded and isolated mainly by their specific gravity and volatility. There is, therefore, a range of distinct chemicals included in each product. This makes rigorous comparisons and identification of specific carcinogens difficult, especially in our modern environment where people are daily exposed to many such products, and is further complicated by exposure to a significant range of other known and potential carcinogens.
"Light naphtha a mixture consisting mainly of straight-chained and cyclic aliphatic hydrocarbons having from five to nine carbon atoms per molecule. Heavy naphtha, a mixture consisting mainly of straight-chained and cyclic aliphatic hydrocarbons having from seven to nine carbons per molecule." "Almost all volatile, lipid-soluble organic chemicals cause general, nonspecific depression of the central nervous system or general anesthesia." The OSHA PEL TWA = 100 parts-per-million (ppm); Health Hazards/Target Organs = eyes, skin, RS, CNS, liver, kidney. Symptoms of acute exposure are dizziness and narcosis with loss of consciousness. The World Health Organization categorizes health effects into three groups: reversible symptoms (Type 1), mild chronic encephalopathy (Type 2) and severe chronic toxic encephalopathy (Type 3).
Topical exposure to naphtha can cause a burning sensation on the skin within a period of minutes to an hour, followed by contact dermatitis—a rash—that can last for days to weeks.
Below are linked few Material Safety Data Sheet (MSDS) specifications for different "naphtha" products containing varying degrees of naphtha, as well as various other chemicals. As well as giving health guidelines, these are some of the few ways to determine what a given product contains.
- JT Baker VM&P Naphtha MSDS.
- Diggers Shellite MSDS
- Shell Ronsonol MSDS source1 source2 formula developed for Ronson
- Links to more MSDS for various camping-stove fuels including several that include naphtha
Benzene in particular is a known high-risk carcinogen, so benzene content is typically specified in the MSDS when it is present in the mixture due to the specifics of the feedstock and distilling process used. Specific detailing of other hydrocarbon species is less common.
Naptha is also extremely volatile and can explode on exposure to high temperature surfaces. in 1999, such an explosion lead to four deaths at the Avon Refinery in Martinez, California.
# Properties
## Physical
Naphtha's molecular weight is 100–215 g/mol. Its density is 750-785 kg/m3, and boiling point is 160-220°C. Vapor pressure is less than 666 Pa (5 torr; 5 mmHg). Naphtha is colorless (kerosene odor) or red-brown (aromatic odor) liquid and is insoluble in water. It is incompatible with strong oxidizers.
# Production in refineries
Naphtha is obtained in petroleum refineries as one of the intermediate products from the distillation of crude oil. It is a liquid intermediate between the light gases in the crude oil and the heavier liquid kerosene. Naphthas are volatile, flammable and have a specific gravity of about 0.7. The generic name 'naphtha' describes a range of different refinery intermediate products used in different applications. To complicate the matter further, similar naphtha types are often referred to by different names.
The different naphthas are distinguished by:
- Density (g/ml or specific gravity)
- PONA, PIONA or PIANO analysis, measured by detailed capillary gas chromatography (usually in volume percent but can also be in weight percent):
Paraffin content (volume percent)
Isoparaffin content (only in a PIONA analysis)
Olefins content (volume percent)
Naphthenes content (volume percent)
Aromatics content (volume percent)
- Paraffin content (volume percent)
- Isoparaffin content (only in a PIONA analysis)
- Olefins content (volume percent)
- Naphthenes content (volume percent)
- Aromatics content (volume percent)
# Different types
## Paraffinic
Generally speaking, less dense ("lighter") naphthas will have a higher paraffin content. These are therefore also referred to as paraffinic naphtha. The main application for these naphthas is as a feedstock in the petrochemical production of olefins. This is also the reason they are sometimes referred to as "light distillate feedstock" or LDF (These naphtha types can also be called "straight run gasoline"/SRG or "light virgin naphtha"/LVN).
When used as feedstock in petrochemical steam crackers, naphtha is heated in the presence of water vapour and the absence of oxygen or air until the hydrocarbon molecules break apart. The primary products of the cracking process are olefins (ethylene / ethene, propylene / propene and butadiene). When naphtha is used as a feedstock in catalytic reforming the primary products are aromatics including benzene, xylene, and toluene. The olefins are used as feedstocks for derivative units that produce plastics (polyethylene and polypropylene for example), synthetic fiber precursors (acrylonitrile), industrial chemicals (glycols for instance) while the aromatics are used for octane boosting in fuel blending as well as polyethylene terephthalate PET feedstock and paint and coating solvents.
## Heavy
The "heavier" or rather denser types are usually richer in naphthenes and aromatics and therefore also referred to as N&As. These can also be used in the petrochemical industry but more often are used as a feedstock for refinery catalytic reformers where they convert the lower octane naphtha to a higher octane product called reformate. Alternative names for these types are Straight Run Benzene (SRB) or Heavy Virgin Naphtha (HVN).
# Other applications
Naphthas are also used in other applications such as:
- An unprocessed component (in contrast to reforming above) in the production of petrol/motor gasoline
- Industrial solvents and cleaning fluids
- A commonly available general purpose solvent designated as "VM&P" naphtha, which stands for "varnish makers' and painters'"
- An oil painting medium
- The sole ingredient in the home cleaning fluid Energine, which has been discontinued
- An ingredient in shoe polish
- An ingredient in some lighter fluids for wick type lighters such as Zippo lighters
- An adulterant to petrol
- A fuel for portable stoves and lanterns, sold in North America as White gas, camp fuel or Coleman fuel
- Historically, as a probable ingredient in Greek fire (together with grease, oil, sulfur, and naturally occurring saltpeter from the desert)
- A fuel for fire spinning, fire juggling, or other fire performance equipment which creates a brighter and cleaner yet shorter burn
- To lightly wear the finish (polish) off guitars when preparing "relic" instruments
- As a coating for elemental lithium metal, to prevent oxidation (mineral oil is also used for this purpose)
- As a fuel in gas turbine unit
- As the working fluid (and sometimes, fuel) in the (external combustion) naphtha engine.
- As a cleaning solution for watch parts during servicing.
In medieval times, pots containing naphtha were used in battle as a form of primitive grenade. In Ancient China, monks used forms of naphtha to prepare in religious ceremonies such as Chimbohduh.
Naphtha is used in the furniture industry on "works in progress" to see temporarily (until the naphtha evaporates) how the patina will look when the piece is oiled and/or aged. It is useful in matching adjacent boards for a join, primarily with tabletops, panels and shelves.
# Examples in daily life
Shellite (Australia), also known as white gas (North America), white spirit (outside the UK) or Coleman fuel, is a white liquid with a hydrocarbon odour. Shellite has a freeze point lower than −30 °C (−22 °F), and a boiling point of 47 °C (116.6 °F). The composition of shellite is 95% paraffins and naphthenes, less than 5% aromatic hydrocarbons and less than 0.5% benzene. It is highly flammable and due to its low flashpoint is used in many low pressure camping stoves. Shellite is also a fast drying solvent used for cleaning metal, hard plastic and painted surfaces.
Ronsonol is a brand name used in North America, for a product marketed principally as a refill fluid for cigarette lighters and having a flashpoint of about 6 °C (42.8 °F). | Naphtha
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Naphtha (/[invalid input: 'icon']ˈnæfθə/ or /ˈnæpθə/) normally refers to a number of flammable liquid mixtures of hydrocarbons, i.e., a component of natural gas condensate or a distillation product from petroleum, coal tar or peat boiling in a certain range and containing certain hydrocarbons. It is a broad term covering among the lightest and most volatile fractions of the liquid hydrocarbons in petroleum. Naphtha is a colorless to reddish-brown volatile aromatic liquid, very similar to gasoline.
In petroleum engineering, full range naphtha is defined as the fraction of hydrocarbons in petroleum boiling between 30 °C and 200 °C.[1] It consists of a complex mixture of hydrocarbon molecules generally having between 5 and 12 carbon atoms. It typically constitutes 15–30% of crude oil, by weight. Light naphtha is the fraction boiling between 30 °C and 90 °C and consists of molecules with 5–6 carbon atoms. Heavy naphtha boils between 90 °C and 200 °C and consists of molecules with 6–12 carbons.
Naphtha is used primarily as feedstock for producing high octane gasoline (via the catalytic reforming process). It is also used in the bitumen mining industry as a diluent, the petrochemical industry for producing olefins in steam crackers, and the chemical industry for solvent (cleaning) applications. Common products made with it include lighter fluid, fuel for camp stoves, and some cleaning solvents.
# Etymology
The word naphtha came from Latin and Greek where it derived from Persian.[2] In Ancient Greek, it was used to refer to any sort of petroleum or pitch. It appears in Arabic as "nafţ" (نَفْط) ("petroleum"), and in Hebrew as "neft" (נֵפְט). Arabs and Persians have used and distilled petroleum for tar and fuel from ancient times, as attested in local Greek and Roman histories of the region.
The second book of the Maccabees in the Septuagint, part of the Old Testament canon in some Christian denominations, uses the word "naphtha" to refer to a miraculous flammable liquid. This account says that Nehemiah and the levitical priests associated with him called the liquid "nephthar," meaning "purification," but "most people" call it naphtha(or Nephi).[3]
Naphtha is the root of the word naphthalene. The second syllable of "naphtha" can also be recognised in phthalate.
It also enters the word napalm from "naphthenic acid and palmitic acid", as the first napalm was made from a mixture of naphthenic acid with aluminium and magnesium salts of palmitic acid.
In older usage, "naphtha" simply meant crude oil, but this usage is now obsolete in English.
The Ukrainian and Belarusian word нафта (lit. nafta), the Russian word нефть (lit. neft') and the Persian naft ( نفت) mean "crude oil". Also, in Italy, Czech Republic, Serbia, Bosnia-Herzegovina, Croatia, Slovenia nafta (нафта in Serbian Cyrillic transcription) is colloquially used to indicate diesel fuel and crude oil. In Slovakia, nafta was historically used for both diesel fuel and crude oil, but its use for crude oil is now obsolete[4] and it generally indicates diesel fuel (crude oil is referred to as ropa[5]). In Bulgarian, nafta means diesel fuel, while neft means crude oil. "Nafta" is also used in Argentina and Uruguay to refer to gasoline. In Poland, the "birthplace" of petroleum industry, word "nafta" means kerosene
There is a conjecture that the Greek word naphtha came from the Indo-Iranian god name Apam Napat, which occurs in Vedic and in Avestic.[6]
# Health and safety considerations
Forms of naphtha may be carcinogenic, and frequently products sold as naphtha contain some impurities which may also have harmful properties of their own.[7][8]
Like many hydrocarbon products, they are products of a refining process in which a complex soup of chemicals is broken into another range of chemicals, which are then graded and isolated mainly by their specific gravity and volatility. There is, therefore, a range of distinct chemicals included in each product. This makes rigorous comparisons and identification of specific carcinogens difficult, especially in our modern environment where people are daily exposed to many such products, and is further complicated by exposure to a significant range of other known and potential carcinogens.[9]
"Light naphtha [is] a mixture consisting mainly of straight-chained and cyclic aliphatic hydrocarbons having from five to nine carbon atoms per molecule. Heavy naphtha, a mixture consisting mainly of straight-chained and cyclic aliphatic hydrocarbons having from seven to nine carbons per molecule."[10] "Almost all volatile, lipid-soluble organic chemicals cause general, nonspecific depression of the central nervous system or general anesthesia."[11] The OSHA PEL TWA = 100 parts-per-million (ppm); Health Hazards/Target Organs = eyes, skin, RS, CNS, liver, kidney. Symptoms of acute exposure are dizziness and narcosis with loss of consciousness. The World Health Organization categorizes health effects into three groups: reversible symptoms (Type 1), mild chronic encephalopathy (Type 2) and severe chronic toxic encephalopathy (Type 3).
Topical exposure to naphtha can cause a burning sensation on the skin within a period of minutes to an hour, followed by contact dermatitis—a rash—that can last for days to weeks.
Below are linked few Material Safety Data Sheet (MSDS) specifications for different "naphtha" products containing varying degrees of naphtha, as well as various other chemicals. As well as giving health guidelines, these are some of the few ways to determine what a given product contains.
- JT Baker VM&P Naphtha MSDS.
- Diggers Shellite MSDS
- Shell Ronsonol MSDS source1 source2 formula developed for Ronson
- Links to more MSDS for various camping-stove fuels including several that include naphtha
Benzene in particular is a known high-risk carcinogen, so benzene content is typically specified in the MSDS when it is present in the mixture due to the specifics of the feedstock and distilling process used. Specific detailing of other hydrocarbon species is less common.[citation needed]
Naptha is also extremely volatile and can explode on exposure to high temperature surfaces. in 1999, such an explosion lead to four deaths at the Avon Refinery in Martinez, California.
# Properties
## Physical
Naphtha's molecular weight is 100–215 g/mol. Its density is 750-785 kg/m3, and boiling point is 160-220°C. Vapor pressure is less than 666 Pa (5 torr; 5 mmHg). Naphtha is colorless (kerosene odor) or red-brown (aromatic odor) liquid and is insoluble in water. It is incompatible with strong oxidizers.[citation needed]
# Production in refineries
Naphtha is obtained in petroleum refineries as one of the intermediate products from the distillation of crude oil. It is a liquid intermediate between the light gases in the crude oil and the heavier liquid kerosene.[12] Naphthas are volatile, flammable and have a specific gravity of about 0.7. The generic name 'naphtha' describes a range of different refinery intermediate products used in different applications. To complicate the matter further, similar naphtha types are often referred to by different names.
The different naphthas are distinguished by:
- Density (g/ml or specific gravity)
- PONA, PIONA or PIANO analysis, measured by detailed capillary gas chromatography (usually in volume percent but can also be in weight percent):
Paraffin content (volume percent)
Isoparaffin content (only in a PIONA analysis)
Olefins content (volume percent)
Naphthenes content (volume percent)
Aromatics content (volume percent)
- Paraffin content (volume percent)
- Isoparaffin content (only in a PIONA analysis)
- Olefins content (volume percent)
- Naphthenes content (volume percent)
- Aromatics content (volume percent)
# Different types
## Paraffinic
Generally speaking, less dense ("lighter") naphthas will have a higher paraffin content. These are therefore also referred to as paraffinic naphtha. The main application for these naphthas is as a feedstock in the petrochemical production of olefins. This is also the reason they are sometimes referred to as "light distillate feedstock" or LDF (These naphtha types can also be called "straight run gasoline"/SRG or "light virgin naphtha"/LVN).
When used as feedstock in petrochemical steam crackers, naphtha is heated in the presence of water vapour and the absence of oxygen or air until the hydrocarbon molecules break apart. The primary products of the cracking process are olefins (ethylene / ethene, propylene / propene and butadiene). When naphtha is used as a feedstock in catalytic reforming the primary products are aromatics including benzene, xylene, and toluene. The olefins are used as feedstocks for derivative units that produce plastics (polyethylene and polypropylene for example), synthetic fiber precursors (acrylonitrile), industrial chemicals (glycols for instance) while the aromatics are used for octane boosting in fuel blending as well as polyethylene terephthalate PET feedstock and paint and coating solvents.
## Heavy
The "heavier" or rather denser types are usually richer in naphthenes and aromatics and therefore also referred to as N&As. These can also be used in the petrochemical industry but more often are used as a feedstock for refinery catalytic reformers where they convert the lower octane naphtha to a higher octane product called reformate. Alternative names for these types are Straight Run Benzene (SRB) or Heavy Virgin Naphtha (HVN).
# Other applications
Naphthas are also used in other applications such as:
- An unprocessed component (in contrast to reforming above) in the production of petrol/motor gasoline
- Industrial solvents and cleaning fluids
- A commonly available general purpose solvent designated as "VM&P" naphtha, which stands for "varnish makers' and painters'"
- An oil painting medium
- The sole ingredient in the home cleaning fluid Energine, which has been discontinued
- An ingredient in shoe polish
- An ingredient in some lighter fluids for wick type lighters such as Zippo lighters
- An adulterant to petrol
- A fuel for portable stoves and lanterns, sold in North America as White gas, camp fuel or Coleman fuel
- Historically, as a probable ingredient in Greek fire (together with grease, oil, sulfur, and naturally occurring saltpeter from the desert)
- A fuel for fire spinning, fire juggling, or other fire performance equipment which creates a brighter and cleaner yet shorter burn
- To lightly wear the finish (polish) off guitars when preparing "relic" instruments
- As a coating for elemental lithium metal, to prevent oxidation (mineral oil is also used for this purpose)
- As a fuel in gas turbine unit
- As the working fluid (and sometimes, fuel) in the (external combustion) naphtha engine.
- As a cleaning solution for watch parts during servicing.
In medieval times, pots containing naphtha were used in battle as a form of primitive grenade. In Ancient China, monks used forms of naphtha to prepare in religious ceremonies such as Chimbohduh.[citation needed]
Naphtha is used in the furniture industry on "works in progress" to see temporarily (until the naphtha evaporates) how the patina will look when the piece is oiled and/or aged. It is useful in matching adjacent boards for a join, primarily with tabletops, panels and shelves.
# Examples in daily life
Shellite (Australia), also known as white gas (North America), white spirit (outside the UK) or Coleman fuel, is a white liquid with a hydrocarbon odour. Shellite has a freeze point lower than −30 °C (−22 °F), and a boiling point of 47 °C (116.6 °F). The composition of shellite is 95% paraffins and naphthenes, less than 5% aromatic hydrocarbons and less than 0.5% benzene. It is highly flammable and due to its low flashpoint is used in many low pressure camping stoves. Shellite is also a fast drying solvent used for cleaning metal, hard plastic and painted surfaces.
Ronsonol is a brand name used in North America, for a product marketed principally as a refill fluid for cigarette lighters and having a flashpoint of about 6 °C (42.8 °F). | https://www.wikidoc.org/index.php/Acute_varnish_makers%27_and_painters%27_Naptha | |
c5338a84271a8ca0edbe6617493223f0f7683a84 | wikidoc | Acyclic | Acyclic
Acyclic can refer to:
- in chemistry, a compound which is not cyclic, e.g. alkanes and acyclic aliphatic compounds
- in mathematics:
a directed acyclic graph
a chain complex in which all reduced homology groups are zero
- a directed acyclic graph
- a chain complex in which all reduced homology groups are zero | Acyclic
Acyclic can refer to:
- in chemistry, a compound which is not cyclic, e.g. alkanes and acyclic aliphatic compounds
- in mathematics:
a directed acyclic graph
a chain complex in which all reduced homology groups are zero
- a directed acyclic graph
- a chain complex in which all reduced homology groups are zero
Template:Disambig
Template:WS | https://www.wikidoc.org/index.php/Acyclic | |
933b14e9d0f66be2e3c23f621be1078db61c6fa6 | wikidoc | Adenoid | Adenoid
# Overview
Adenoids (or pharyngeal tonsils, or nasopharyngeal tonsils) are a mass of lymphoid tissue situated at the very back of the nose, in the roof of the nasopharynx, where the nose blends into the mouth.
Normally, in children, they make a soft mound in the roof and posterior wall of the nasopharynx, just above and behind the uvula.
# Function
Adenoids are part of the immune system. Like all lymphoid tissue, they trap infectious agents like viruses and bacteria, and they produce antibodies.
Since the adenoids are located at the back of the nasal airway, they provide defense against inhaled substances.
This function decreases with age as the adenoids shrink. Because adenoids do ordinarily shrink by late childhood, the problems caused by enlarged adenoids rarely occur in adults.
# Pathology
Enlarged adenoids, or adenoid hypertrophy, can become nearly the size of a ping pong ball and completely block airflow through the nasal passages.
Even if enlarged adenoids are not substantial enough to physically block the back of the nose, they can obstruct airflow enough so that breathing through the nose requires an uncomfortable amount of work, and inhalation occurs instead through an open mouth.
Adenoids can also obstruct the nasal airway enough to affect the voice without actually stopping nasal airflow altogether.
# Removal of the adenoids
Surgical removal of the adenoids is a procedure called adenoidectomy.
Carried out through the mouth under a general anaesthetic (or less commonly a topical), adenoidectomy involves the adenoids being curetted, cauterised, lasered, or otherwise ablated.
# Histology
Adenoids, unlike other types of tonsils, have pseudostratified columnar epithelium.
They also differ from the other tonsil types by lacking crypts.
The adenoids are often removed along with the tonsils. This can cause a very sore throat for about a week and rather unpleasant breath. Most people's adenoids are not even in use after a person's third year, but if they cause problems they must be taken out or they may otherwise shrink. | Adenoid
Template:Infobox Anatomy
# Overview
Adenoids (or pharyngeal tonsils, or nasopharyngeal tonsils) are a mass of lymphoid tissue situated at the very back of the nose, in the roof of the nasopharynx, where the nose blends into the mouth.
Normally, in children, they make a soft mound in the roof and posterior wall of the nasopharynx, just above and behind the uvula.
# Function
Adenoids are part of the immune system. Like all lymphoid tissue, they trap infectious agents like viruses and bacteria, and they produce antibodies.
Since the adenoids are located at the back of the nasal airway, they provide defense against inhaled substances.
This function decreases with age as the adenoids shrink. Because adenoids do ordinarily shrink by late childhood, the problems caused by enlarged adenoids rarely occur in adults.
# Pathology
Enlarged adenoids, or adenoid hypertrophy, can become nearly the size of a ping pong ball and completely block airflow through the nasal passages.
Even if enlarged adenoids are not substantial enough to physically block the back of the nose, they can obstruct airflow enough so that breathing through the nose requires an uncomfortable amount of work, and inhalation occurs instead through an open mouth.
Adenoids can also obstruct the nasal airway enough to affect the voice without actually stopping nasal airflow altogether.
# Removal of the adenoids
Surgical removal of the adenoids is a procedure called adenoidectomy.
Carried out through the mouth under a general anaesthetic (or less commonly a topical), adenoidectomy involves the adenoids being curetted, cauterised, lasered, or otherwise ablated.
# Histology
Adenoids, unlike other types of tonsils, have pseudostratified columnar epithelium.[1]
They also differ from the other tonsil types by lacking crypts.
The adenoids are often removed along with the tonsils. This can cause a very sore throat for about a week and rather unpleasant breath. Most people's adenoids are not even in use after a person's third year, but if they cause problems they must be taken out or they may otherwise shrink. | https://www.wikidoc.org/index.php/Adenoid | |
74cd6bb5814afc417bc06f60964bd91a648f0586 | wikidoc | Adhesin | Adhesin
Adherence is often an essential step in bacterial pathogenesis or infection, required for colonizing a new host. To effectively adhere to host surfaces, many bacteria produce multiple adherence factors called adhesins. For example, nontypeable Haemophilus influenzae expresses the adhesins Hia, Hap, Oap and a hemagglutinating pili.
Adhesins are attractive vaccine candidates because they are often essential to infection and are surface-located, making them readily accessible to antibodies.
The effectiveness of anti-adhesin antibodies is illustrated by studies with FimH, the adhesin of uropathogenic Escherichia coli (UPEC). In animal models, passive immunization with anti FimH-antibodies and vaccination with the protein significantly reduced colonization by UPEC. Moreover, the Bordetella pertussis adhesins FHA and pertactin are components of 3 of the 4 acellular pertussis vaccines currently licensed for use in the U.S. | Adhesin
Adherence is often an essential step in bacterial pathogenesis or infection, required for colonizing a new host.[1] To effectively adhere to host surfaces, many bacteria produce multiple adherence factors called adhesins. For example, nontypeable Haemophilus influenzae expresses the adhesins Hia, Hap, Oap and a hemagglutinating pili.
Adhesins are attractive vaccine candidates because they are often essential to infection and are surface-located, making them readily accessible to antibodies.
The effectiveness of anti-adhesin antibodies is illustrated by studies with FimH, the adhesin of uropathogenic Escherichia coli (UPEC). In animal models, passive immunization with anti FimH-antibodies and vaccination with the protein significantly reduced colonization by UPEC.[2] Moreover, the Bordetella pertussis adhesins FHA and pertactin are components of 3 of the 4 acellular pertussis vaccines currently licensed for use in the U.S. | https://www.wikidoc.org/index.php/Adhesin | |
2840a7d3b87cbb0cdf600062058cf74399520dcd | wikidoc | Adipose | Adipose
In anatomy, adipose tissue or fat is loose connective tissue composed of adipocytes. Its main role is to store energy in the form of fat, although it also cushions and insulates the body. Obesity in humans and most animals is not dependent on the amount of body weight, but on the amount of body fat—specifically adipose tissue. Two types of adipose tissue exist: white adipose tissue (WAT) and brown adipose tissue (BAT). Adipose tissue also serves as an important endocrine organ by producing recently-discovered hormones such as leptin, resistin and the cytokine TNFα. The formation of adipose tissue appears to be controlled by the adipose gene.
# Anatomical features
In humans, adipose tissue is located beneath the skin and is also found around internal organs. Adipose tissue is found in specific locations, which are referred to as 'adipose depots'. Adipose tissue contains several cell types, with the highest percentage of cells being adipocytes, which contain fat droplets. Other cell types include fibroblasts, macrophages and endothelial cells. Adipose tissue contains many small blood vessels. In the integumentary system, which includes the skin, it accumulates in the deepest level, the subcutaneous layer, providing insulation from heat and cold. Around organs, it provides protective padding. However, its main function is to be a reserve of lipids, which can be burned to meet the energy needs of the body. Adipose depots in different parts of the body have different biochemical profiles.
In a severely obese person, excess adipose tissue hanging downward from the abdomen is referred to as a panniculus (or pannus). A panniculus complicates surgery of the morbidly obese. The panniculus may remain as a literal "apron of skin" if a severely obese person quickly loses large amounts of weight (a common result of gastric bypass surgery). This condition cannot easily be corrected through diet and exercise, as the panniculus consists of adipocytes and other supporting cell types shrunken to their minimum volume and diameter. Reconstructive surgery is one way to fix the problem.
In mice, there are eight major adipose depots, four of which are within the abdominal cavity: the paired gonadal depots are attached to the uterus and ovaries in females and the epididymis and testes in males, the paired retroperitoneal depots are found along the dorsal wall of the abdomen, surrounding the kidney, and when massive extend into the pelvis. The mesenteric depot forms a glue-like web that supports the intestines, and the omental depot, which originates near the stomach and spleen and when massive extends into the ventral abdomen. Both the mesenteric and omental depots incorporate much lymphoid tissue as lymph nodes and milky spots respectively. The two superficial depots are the paired inguinal depots, which are found anterior to the upper segment of the hind limbs (underneath the skin) and the subscapular depots, paired medial mixtures of brown adipose tissue adjacent to regions of white adipose tissue, which are found under the skin between the dorsal crests of the scapulae. The layer of brown adipose tissue in this depot is often covered by a “frosting” of white adipose tissue, sometimes these two types of fat (brown and white) are hard to distinguish. The inguinal depots enclose the inguinal group of lymph nodes. Minor depots include the pericardial which surrounds the heart, and the paired popliteal depots, between the major muscles behind the knees, each containing one large lymph node(Pond 1998). Of all the depots in the mouse, the gonadal depots are the largest and the most easily dissected (Cinti, 1999), comprising about 30% of dissectible fat, e.g., (Bachmanov et al. 2001).
# Physiology
Free fatty acid is "liberated" from lipoproteins by lipoprotein lipase (LPL) and enters the adipocyte, where it is reassembled into triglycerides by esterising it onto glycerol. Human fat tissue contains about 87% lipids.
In humans, lipolysis is controlled though the balanced control of lipolytic B-adrenergic receptors and a2A-andronergic receptor mediated antilipolysis.
Fat is not laid down when there is a surplus available and stored passively until it is needed; rather it is constantly being stored in and released from each cell.
Fat cells have an important physiological role in maintaining triglyceride and free fatty acid levels, as well as determining insulin resistance. Abdominal fat has a different metabolic profile—being more prone to induce insulin resistance. This explains to a large degree why central obesity is a marker of impaired glucose tolerance and is an independent risk factor for cardiovascular disease (even in the absence of diabetes mellitus and hypertension).
Recent advances in biotechnology have allowed for the harvesting of adult stem cells from adipose tissue, allowing stimulation of tissue regrowth using a patient's own cells. The use of a patient's own cells reduces the chance of tissue rejection and avoids the ethical issues associated with the use of human embryonic stem cells.
Adipose tissue is the greatest peripheral source of aromatase in both males and females contributing to the production of estradiol.
Hormones secreted by adipose tissue include:
- Adiponectin
- Resistin
- Angiotensin
- Plasminogen activator inhibitor-1 (PAI-1)
- TNFα
- IL-6
- Leptin
- Estradiol (E2)
Adipose tissues also secret a type of cytokines (cell-to-cell signalling proteins) called adipokines (adipocytokines) which play a role in obesity-associated complications.
## Brown fat
A specialised form of adipose tissue in human infants, and some animals, is brown fat or brown adipose tissue. It is located mainly around the neck and large blood vessels of the thorax. This specialised tissue can generate heat by "uncoupling" the respiratory chain of oxidative phosphorylation within mitochondria, leading to the breakdown of fatty acids. This thermogenic process may be vital in neonates exposed to the cold, who then require this thermogenesis to keep warm as they are unable to shiver, or take other actions to keep themselves warm.
Attempts to stimulate this process pharmacologically have so far been unsuccessful, but might in the future be a target of weight loss therapy.
## Genetics
In 2007, researchers isolated the adipose gene, which apparently serves to keep animals lean during times of plenty. Increased adipose gene activity was associated with slimmer individuals.
# Cultural and social role
Excess adipose tissue on a human can lead to medical problems; however, a round or large figure does not of itself imply a medical problem, and is sometimes not primarily caused by adipose tissue. For a discussion of the aesthetic and medical significance of body shape, see dieting and obesity.
# Additional images
- diagrammatic sectional view of the skin (magnified).
- Yellow adipose tissue in paraffin section | Adipose
In anatomy, adipose tissue or fat is loose connective tissue composed of adipocytes. Its main role is to store energy in the form of fat, although it also cushions and insulates the body. Obesity in humans and most animals is not dependent on the amount of body weight, but on the amount of body fat—specifically adipose tissue. Two types of adipose tissue exist: white adipose tissue (WAT) and brown adipose tissue (BAT). Adipose tissue also serves as an important endocrine organ[1] by producing recently-discovered hormones such as leptin, resistin and the cytokine TNFα. The formation of adipose tissue appears to be controlled by the adipose gene.
# Anatomical features
In humans, adipose tissue is located beneath the skin and is also found around internal organs. Adipose tissue is found in specific locations, which are referred to as 'adipose depots'. Adipose tissue contains several cell types, with the highest percentage of cells being adipocytes, which contain fat droplets. Other cell types include fibroblasts, macrophages and endothelial cells. Adipose tissue contains many small blood vessels. In the integumentary system, which includes the skin, it accumulates in the deepest level, the subcutaneous layer, providing insulation from heat and cold. Around organs, it provides protective padding. However, its main function is to be a reserve of lipids, which can be burned to meet the energy needs of the body. Adipose depots in different parts of the body have different biochemical profiles.
In a severely obese person, excess adipose tissue hanging downward from the abdomen is referred to as a panniculus (or pannus). A panniculus complicates surgery of the morbidly obese. The panniculus may remain as a literal "apron of skin" if a severely obese person quickly loses large amounts of weight (a common result of gastric bypass surgery). This condition cannot easily be corrected through diet and exercise, as the panniculus consists of adipocytes and other supporting cell types shrunken to their minimum volume and diameter. Reconstructive surgery is one way to fix the problem.
In mice, there are eight major adipose depots, four of which are within the abdominal cavity: the paired gonadal depots are attached to the uterus and ovaries in females and the epididymis and testes in males, the paired retroperitoneal depots are found along the dorsal wall of the abdomen, surrounding the kidney, and when massive extend into the pelvis. The mesenteric depot forms a glue-like web that supports the intestines, and the omental depot, which originates near the stomach and spleen and when massive extends into the ventral abdomen. Both the mesenteric and omental depots incorporate much lymphoid tissue as lymph nodes and milky spots respectively. The two superficial depots are the paired inguinal depots, which are found anterior to the upper segment of the hind limbs (underneath the skin) and the subscapular depots, paired medial mixtures of brown adipose tissue adjacent to regions of white adipose tissue, which are found under the skin between the dorsal crests of the scapulae. The layer of brown adipose tissue in this depot is often covered by a “frosting” of white adipose tissue, sometimes these two types of fat (brown and white) are hard to distinguish. The inguinal depots enclose the inguinal group of lymph nodes. Minor depots include the pericardial which surrounds the heart, and the paired popliteal depots, between the major muscles behind the knees, each containing one large lymph node(Pond 1998). Of all the depots in the mouse, the gonadal depots are the largest and the most easily dissected (Cinti, 1999), comprising about 30% of dissectible fat, e.g., (Bachmanov et al. 2001).
# Physiology
Free fatty acid is "liberated" from lipoproteins by lipoprotein lipase (LPL) and enters the adipocyte, where it is reassembled into triglycerides by esterising it onto glycerol. Human fat tissue contains about 87% lipids.
In humans, lipolysis is controlled though the balanced control of lipolytic B-adrenergic receptors and a2A-andronergic receptor mediated antilipolysis.
Fat is not laid down when there is a surplus available and stored passively until it is needed; rather it is constantly being stored in and released from each cell.
Fat cells have an important physiological role in maintaining triglyceride and free fatty acid levels, as well as determining insulin resistance. Abdominal fat has a different metabolic profile—being more prone to induce insulin resistance. This explains to a large degree why central obesity is a marker of impaired glucose tolerance and is an independent risk factor for cardiovascular disease (even in the absence of diabetes mellitus and hypertension).
Recent advances in biotechnology have allowed for the harvesting of adult stem cells from adipose tissue, allowing stimulation of tissue regrowth using a patient's own cells. The use of a patient's own cells reduces the chance of tissue rejection and avoids the ethical issues associated with the use of human embryonic stem cells.
Adipose tissue is the greatest peripheral source of aromatase in both males and females contributing to the production of estradiol.
Hormones secreted by adipose tissue include:
- Adiponectin
- Resistin
- Angiotensin
- Plasminogen activator inhibitor-1 (PAI-1)
- TNFα
- IL-6
- Leptin
- Estradiol (E2)
Adipose tissues also secret a type of cytokines (cell-to-cell signalling proteins) called adipokines (adipocytokines) which play a role in obesity-associated complications.
## Brown fat
A specialised form of adipose tissue in human infants, and some animals, is brown fat or brown adipose tissue. It is located mainly around the neck and large blood vessels of the thorax. This specialised tissue can generate heat by "uncoupling" the respiratory chain of oxidative phosphorylation within mitochondria, leading to the breakdown of fatty acids. This thermogenic process may be vital in neonates exposed to the cold, who then require this thermogenesis to keep warm as they are unable to shiver, or take other actions to keep themselves warm.[2]
Attempts to stimulate this process pharmacologically have so far been unsuccessful, but might in the future be a target of weight loss therapy.
## Genetics
In 2007, researchers isolated the adipose gene, which apparently serves to keep animals lean during times of plenty. Increased adipose gene activity was associated with slimmer individuals.[3]
# Cultural and social role
Excess adipose tissue on a human can lead to medical problems; however, a round or large figure does not of itself imply a medical problem, and is sometimes not primarily caused by adipose tissue. For a discussion of the aesthetic and medical significance of body shape, see dieting and obesity.
# Additional images
- diagrammatic sectional view of the skin (magnified).
- Yellow adipose tissue in paraffin section | https://www.wikidoc.org/index.php/Adipose | |
0fae751dd87531bed530128c02313d8de3eb10eb | wikidoc | Old age | Old age
# Overview
Old age consists of ages nearing or surpassing the average life span of human beings, and thus the end of the human life cycle. Euphemisms and terms for older people include seniors — chiefly an American usage — or elderly. Some believe there to be prejudice against older people in Western cultures, which is one form of ageism.
Older people have limited regenerative abilities and are more prone to disease, syndromes, and sickness than other adults. For the biology of ageing, see Senescence. The medical study of the aging process is gerontology, and the study of diseases that afflict the elderly is geriatrics.
# Definition
The boundary between middle age and old age cannot be defined exactly because it does not have the same meaning in all societies. In many parts of the world, people are considered old because of certain changes in their activities or social roles. Examples: people may be considered old when they become grandparents, or when they begin to do less or different work — retirement. In the United States and Europe, people are often considered old if they have lived a certain number of years.
Many Americans think of 65 as the beginning of old age because United States workers become eligible at this time to retire with full Social Security benefits at age 65. People in the 65-and-over age group are often called senior citizens. In 2003, the age at which an American citizen becomes eligible for full Social Security benefits began to increase gradually until it reaches 67 in 2027.
There are many stereotypes about elderly people, such as; the use of walking sticks, frequent doctor visits, and sleeping a lot. These can be seen however to be untrue and very judgmental, most old people are very capable of easy mobility and caring for themselves, however there are some illnesses that can be seen to come with old age.
# Demographic changes
Worldwide, the number of people 65 or older is increasing faster than ever before. Most of this increase is occurring in developed countries. In the United States the percentage of people 65 or older increased from 4 percent in 1900 to about 13 percent in the late 1990s. In 1900, only about 3 million of the nation's citizens had reached 65. By 1998, the number of senior citizens had increased to about 34 million. Population experts estimate that more than 50 million Americans — about 17 percent of the population — will be 65 or older in 2020. The number of old people is growing around the world chiefly because more children reach adulthood.
# Life expectancy
In most parts of the world, women live, on average, longer than men. In the United States in the late 1990s, life expectancy at birth was 80 years for women and 77 years for men. American women who were age 65 in the late 1990s could expect to live about 19 additional years. Men who were 65 could expect to live about 16 additional years. | Old age
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Old age consists of ages nearing or surpassing the average life span of human beings, and thus the end of the human life cycle. Euphemisms and terms for older people include seniors — chiefly an American usage — or elderly. Some believe there to be prejudice against older people in Western cultures, which is one form of ageism.
Older people have limited regenerative abilities and are more prone to disease, syndromes, and sickness than other adults. For the biology of ageing, see Senescence. The medical study of the aging process is gerontology, and the study of diseases that afflict the elderly is geriatrics.
# Definition
The boundary between middle age and old age cannot be defined exactly because it does not have the same meaning in all societies. In many parts of the world, people are considered old because of certain changes in their activities or social roles. Examples: people may be considered old when they become grandparents, or when they begin to do less or different work — retirement. In the United States and Europe, people are often considered old if they have lived a certain number of years.
Many Americans think of 65 as the beginning of old age because United States workers become eligible at this time to retire with full Social Security benefits at age 65. People in the 65-and-over age group are often called senior citizens. In 2003, the age at which an American citizen becomes eligible for full Social Security benefits began to increase gradually until it reaches 67 in 2027.
There are many stereotypes about elderly people, such as; the use of walking sticks, frequent doctor visits, and sleeping a lot. These can be seen however to be untrue and very judgmental, most old people are very capable of easy mobility and caring for themselves, however there are some illnesses that can be seen to come with old age.
# Demographic changes
Worldwide, the number of people 65 or older is increasing faster than ever before. Most of this increase is occurring in developed countries. In the United States the percentage of people 65 or older increased from 4 percent in 1900 to about 13 percent in the late 1990s. In 1900, only about 3 million of the nation's citizens had reached 65. By 1998, the number of senior citizens had increased to about 34 million. Population experts estimate that more than 50 million Americans — about 17 percent of the population — will be 65 or older in 2020. The number of old people is growing around the world chiefly because more children reach adulthood.
# Life expectancy
In most parts of the world, women live, on average, longer than men. In the United States in the late 1990s, life expectancy at birth was 80 years for women and 77 years for men. American women who were age 65 in the late 1990s could expect to live about 19 additional years. Men who were 65 could expect to live about 16 additional years. | https://www.wikidoc.org/index.php/Advanced_age | |
fd5c445f51b6befdd156d8ff6b8993a6a1e43ffa | wikidoc | Advaxis | Advaxis
Advaxis is a biotechnology company based in North Brunswick and Princeton , New Jersey which develops Listeria cancer vaccines.
# Development and production
Advaxis uses live genetically modified Listeria monocytogenes to treat cancers, infectious disease and problems of the immune system. With a total of over 10 years of innovative work conducted by Yvonne Paterson, Ph.D., Professor of Microbiology at the University of Pennsylvania, discoveries uncovered the unique capabilities of microbe Listeria. The microbe promotes simultaneous stimulatation of every aspect within the immune system creating a process for coordinating innate, humoral and encourages cellular adaptive immune responses in an extremely effective response to existing cancers and other diseases.
# Testing
Advaxis is the exclusive licensee of a patented broadly enabling Listeria platform technology that can elicit effective anti-tumor responses. The leading Advaxis Listeria vaccine candidate, Lovaxin C, targets cervical cancer and head cancer and neck cancers. Other Listeria vaccines in development target breast cancer, ovarian cancer and lung cancers. Advaxis is entering a Phase I/II clinical trial.
It is important to understand that Advaxis is developing vaccines for treating patients who have already contracted the target disease, such as cervical or breast cancer. In animal models of breast cancer, the data show that the Advaxis Lovaxin B vaccine, composed of the Listeria with the Her2/neu antigen, was able to successfully stop tumor growth.
# Patent
Advaxis in partnership with GlaxoSmithKline laboratories unveloped the information that a non-haemolytic truncated form of Listeriolysin O Protein ((LLO)), a single polypeptide protein secreted by the Gram-positive bacteria Listeria monocytogenes , when fused to an antigen enhances a higher level of immunity protection. The joint invention has been patented.
# Notes
- ↑ "Advaxis Enrolls Patients to Cervical Cancer Vaccine Trial". dBusiness News. Last accessed 05-28-06. Check date values in: |date= (help).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}
- ↑ "Advaxis' Vaccine Candidate to Treat Existing Cervical Cancer". Healthcare and Sales Marketing. Last accessed 05-28-06. Check date values in: |date= (help)
- ↑ "Advaxis". Advaxis website. Last accessed 05-28-06. Check date values in: |date= (help)
- ↑ "Company". Last accessed 05-28-06. Check date values in: |date= (help)
- ↑ Biowire (Last accessed 05-28-06). "Advaxis Enrolls Patients to Cervical Cancer Vaccine Trial". Genetic Engineering News. Check date values in: |date= (help)
- ↑ "Recombinant Listeriolysin-O". Last accessed 05-28-06. Check date values in: |date= (help)
- ↑ "Advaxis and GlaxoSmithKline Biologicals SA Execute License Agreement for Listeriolysin O Protein Technology". BioExchange. Last accessed 05-28-06. Check date values in: |date= (help) | Advaxis
Advaxis is a biotechnology company based in North Brunswick [1] and Princeton [2], New Jersey which develops Listeria cancer vaccines.
# Development and production
Advaxis uses live genetically modified Listeria monocytogenes to treat cancers, infectious disease and problems of the immune system. [3] With a total of over 10 years of innovative work conducted by Yvonne Paterson, Ph.D., Professor of Microbiology at the University of Pennsylvania, discoveries uncovered the unique capabilities of microbe Listeria. The microbe promotes simultaneous stimulatation of every aspect within the immune system creating a process for coordinating innate, humoral [antibodies|antibody] and encourages cellular adaptive immune responses in an extremely effective response to existing cancers and other diseases. [4]
# Testing
Advaxis is the exclusive licensee of a patented broadly enabling Listeria platform technology that can elicit effective anti-tumor responses. The leading Advaxis Listeria vaccine candidate, Lovaxin C, targets cervical cancer and head cancer and neck cancers. Other Listeria vaccines in development target breast cancer, ovarian cancer and lung cancers. Advaxis is entering a Phase I/II clinical trial. [5]
It is important to understand that Advaxis is developing vaccines for treating patients who have already contracted the target disease, such as cervical or breast cancer. In animal models of breast cancer, the data show that the Advaxis Lovaxin B vaccine, composed of the Listeria with the Her2/neu antigen, was able to successfully stop tumor growth.
# Patent
Advaxis in partnership with GlaxoSmithKline laboratories unveloped the information that a non-haemolytic truncated form of Listeriolysin O Protein ((LLO)), a single polypeptide protein secreted by the Gram-positive bacteria Listeria monocytogenes [6], when fused to an antigen enhances a higher level of immunity protection. The joint invention has been patented. [7]
# Notes
- ↑ "Advaxis Enrolls Patients to Cervical Cancer Vaccine Trial". dBusiness News. Last accessed 05-28-06. Check date values in: |date= (help).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}
- ↑ "Advaxis' Vaccine Candidate to Treat Existing Cervical Cancer". Healthcare and Sales Marketing. Last accessed 05-28-06. Check date values in: |date= (help)
- ↑ "Advaxis". Advaxis website. Last accessed 05-28-06. Check date values in: |date= (help)
- ↑ "Company". Last accessed 05-28-06. Check date values in: |date= (help)
- ↑ Biowire (Last accessed 05-28-06). "Advaxis Enrolls Patients to Cervical Cancer Vaccine Trial". Genetic Engineering News. Check date values in: |date= (help)
- ↑ "Recombinant Listeriolysin-O". Last accessed 05-28-06. Check date values in: |date= (help)
- ↑ "Advaxis and GlaxoSmithKline Biologicals SA Execute License Agreement for Listeriolysin O Protein Technology". BioExchange. Last accessed 05-28-06. Check date values in: |date= (help) | https://www.wikidoc.org/index.php/Advaxis | |
39897c888bcfc69028bf4c6a72171517ba33a1f3 | wikidoc | Aerosol | Aerosol
Aerosol technically refers to airborne liquid droplets or solid particles (also called dust or particulate matter (PM)). In casual language, aerosol refers to an aerosol spray can or the output of such a can.
The term aerosol, derives from the fact that matter "floating" in air is a suspension (a mixture in which solid or liquid or combined solid-liquid particles are suspended in a fluid). To differentiate suspensions from true solutions, the term sol evolved—originally meant to cover dispersions of tiny (sub-microscopic) particles in a liquid. With studies of dispersions in air, the term aerosol evolved and now embraces both liquid droplets, solid particles, and combinations of these. An aerosol may come from sources as various as a volcano or an aerosol can.
# Workplace exposure
Concentrated aerosols from substances such as silica, asbestos, and diesel particulate matter are sometimes found in the workplace and have been shown to result in a number of diseases including silicosis and black lung.
Respirators can protect workers from harmful aerosol exposure. The certifies respirators through the National Personal Protective Technology Laboratory to ensure that they protect workers and the public from harmful airborne contaminants.
# Effect on climate
Anthropogenic aerosols, particularly sulfate aerosols from fossil fuel combustion, exert a cooling influence on the climate. The cooling effect of aerosols, however, does not seem to directly counteract the warming induced by greenhouse gases such as carbon dioxide, methane and water vapor and is accounted for in climate models, despite some claims that "global dimming" by aerosols may counteract global warming. | Aerosol
Aerosol technically refers to airborne liquid droplets or solid particles (also called dust or particulate matter (PM)). In casual language, aerosol refers to an aerosol spray can or the output of such a can.
The term aerosol, derives from the fact that matter "floating" in air is a suspension (a mixture in which solid or liquid or combined solid-liquid particles are suspended in a fluid). To differentiate suspensions from true solutions, the term sol evolved—originally meant to cover dispersions of tiny (sub-microscopic) particles in a liquid. With studies of dispersions in air, the term aerosol evolved and now embraces both liquid droplets, solid particles, and combinations of these. An aerosol may come from sources as various as a volcano or an aerosol can.
# Workplace exposure
Concentrated aerosols from substances such as silica, asbestos, and diesel particulate matter are sometimes found in the workplace and have been shown to result in a number of diseases including silicosis and black lung.[1]
Respirators can protect workers from harmful aerosol exposure. The [[National Institute for Occupational Safety and Health] certifies respirators through the National Personal Protective Technology Laboratory to ensure that they protect workers and the public from harmful airborne contaminants.[2]
# Effect on climate
Anthropogenic aerosols, particularly sulfate aerosols from fossil fuel combustion, exert a cooling influence on the climate.[3] The cooling effect of aerosols, however, does not seem to directly counteract the warming induced by greenhouse gases such as carbon dioxide, methane and water vapor and is accounted for in climate models, despite some claims that "global dimming" by aerosols may counteract global warming.[4] | https://www.wikidoc.org/index.php/Aerosol | |
045d3ef131b9cb378c8e6a6997b169e77df3d3c9 | wikidoc | Ageusia | Ageusia
Synonyms and keywords: loss of taste
# Overview
Ageusia (pronounced ay-GOO-see-uh) is the loss of taste functions of the tongue, particularly the inability to detect sweetness, sourness, bitterness, saltiness, and umami (the taste of monosodium glutamate). It is sometimes confused for anosmia - a loss of the sense of smell. Because the tongue can only indicate texture and differentiate between sweet, sour, bitter, salty, and umami most of what is perceived as the sense of taste is actually derived from smell. True aguesia is relatively rare compared to the milder forms of taste loss: hypogeusia and dysgeusia. Hypogeusia represents a partial loss of taste whereas dysgeusia denotes a distortion or alteration of taste.
# Causes
## Neurological Damage
Tissue damage to the nerves that support the tongue can cause ageusia, especially damage to the lingual nerve and the glossopharyngeal nerve. The lingual nerve passes taste for the front two-thirds of the tongue and the glossopharyngeal nerve passes taste for the back third of the tongue. Neurological disorders such as Bell's Palsy, Familial Dysautonomia, and Multiple Sclerosis will cause similar problems to nerve damage, as will certain infectious conditions like primary amoeboid meningoencephalopathy. The lingual nerve (who is a branch of the trigeminal V3 nerve, but carries taste sensation back to the chorda tympani nerve to the geniculate ganglion of the facial nerve) can also be damaged during otologic surgery giving place to a feeling of metal taste.
## Problems with the Endocrine System
Vitamin deficiency, namely vitamins B3 and Zinc, could lead to problems with the Endocrine system, which may in turn lead to taste loss or alteration. Disorders of the Endocrine System such as Cushing's Syndrome, Hypothyroidism and Diabetes Mellitus could lead to similar problems. Ageusia can also be caused by medicinal side-effects from Antirheumatic Drugs such as Penicillamine, Antiproliferative drugs such as Cisplatin, ACE Inhibitors, and other drugs including Azelastine, Clarithromycin and Zopiclone.
## Other Causes
Local damage and inflammation that interferes with the taste buds or local nervous system such as that stemming from radiation therapy, glossitis, tobacco abuse, and denture use will also cause ageusia. Other known causes of ageusia include loss of taste sensitivity from aging (resulting in a difficulty detecting salty or bitter taste), Anxiety Disorder, Cancer, Renal Failure and Hepatic failure.
# Diagnosis
In order to discover the extent of the ageusia, a scientist attempts to discern the minimum level of a chemical that a patient can detect by taste. Patients may also be asked to compare various concentrations of chemicals in order that the doctor may ascertain what level of intensity that the patient can differentiate. Various methods are used, including the "sip, spit, and rinse" test as well as direct application of chemicals to the tongue. | Ageusia
Template:SignSymptom infobox
Template:Search infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: loss of taste
# Overview
Ageusia (pronounced ay-GOO-see-uh) is the loss of taste functions of the tongue, particularly the inability to detect sweetness, sourness, bitterness, saltiness, and umami (the taste of monosodium glutamate). It is sometimes confused for anosmia - a loss of the sense of smell. Because the tongue can only indicate texture and differentiate between sweet, sour, bitter, salty, and umami most of what is perceived as the sense of taste is actually derived from smell. True aguesia is relatively rare compared to the milder forms of taste loss: hypogeusia and dysgeusia. Hypogeusia represents a partial loss of taste whereas dysgeusia denotes a distortion or alteration of taste.
# Causes
## Neurological Damage
Tissue damage to the nerves that support the tongue can cause ageusia, especially damage to the lingual nerve and the glossopharyngeal nerve. The lingual nerve passes taste for the front two-thirds of the tongue and the glossopharyngeal nerve passes taste for the back third of the tongue. Neurological disorders such as Bell's Palsy, Familial Dysautonomia, and Multiple Sclerosis will cause similar problems to nerve damage, as will certain infectious conditions like primary amoeboid meningoencephalopathy. The lingual nerve (who is a branch of the trigeminal V3 nerve, but carries taste sensation back to the chorda tympani nerve to the geniculate ganglion of the facial nerve) can also be damaged during otologic surgery giving place to a feeling of metal taste.
## Problems with the Endocrine System
Vitamin deficiency, namely vitamins B3 and Zinc, could lead to problems with the Endocrine system, which may in turn lead to taste loss or alteration. Disorders of the Endocrine System such as Cushing's Syndrome, Hypothyroidism and Diabetes Mellitus could lead to similar problems. Ageusia can also be caused by medicinal side-effects from Antirheumatic Drugs such as Penicillamine, Antiproliferative drugs such as Cisplatin, ACE Inhibitors, and other drugs including Azelastine, Clarithromycin and Zopiclone.
## Other Causes
Local damage and inflammation that interferes with the taste buds or local nervous system such as that stemming from radiation therapy, glossitis, tobacco abuse, and denture use will also cause ageusia. Other known causes of ageusia include loss of taste sensitivity from aging (resulting in a difficulty detecting salty or bitter taste), Anxiety Disorder, Cancer, Renal Failure and Hepatic failure.
# Diagnosis
In order to discover the extent of the ageusia, a scientist attempts to discern the minimum level of a chemical that a patient can detect by taste. Patients may also be asked to compare various concentrations of chemicals in order that the doctor may ascertain what level of intensity that the patient can differentiate. Various methods are used, including the "sip, spit, and rinse" test as well as direct application of chemicals to the tongue. | https://www.wikidoc.org/index.php/Ageusia | |
93dda0b5b06e9ae4d3c964a9e6ccba08a6169454 | wikidoc | Agnatha | Agnatha
Agnatha (Greek, "no jaws") is a paraphyletic superclass of jawless fish in the phylum Chordata, subphylum Vertebrata. It has existed since the Cambrian, and continues to live now. There are two extant groups of jawless fish (sometimes called cyclostomes), the lampreys and the hagfish, with about 100 species in total. Although they are in the subphylum Vertebrata, hagfish technically do not have vertebrae; they are sometimes classified in Craniata. In addition to the absence of jaws, Agnatha are characterised by absence of paired fins; the presence of a notochord both in larvae and adults; and seven or more paired gill pouches. There is a light sensitive pineal eye (homologous to the pineal gland in mammals). All living and most extinct Agnatha do not have an identifiable stomach or any appendages. Fertilization and development are both external. There is no parental care in the Agnatha class. The Agnatha are ectothermic, with a cartilaginous skeleton, and the heart contains 2 chambers.
Although they are superficially similar, many of these similarities are probably shared basal characteristics of ancient vertebrates, and modern classifications tend to place hagfish into a separate group (the Myxini or Hyperotreti), with the lampreys (Hyperoartii) being more closely related to the jawed fishes.
# Respiratory system
Agnathans are characterized by seven or more pairs of gill pouches. The bronchial arches supporting the gill pouches lie close to the body surface.
# Metabolism
Agnathans are ectothermic or cold blooded, meaning they do not have to warm themselves through eating. Therefore, Agnathan metabolism is slow as well as the fact that Agnathans do not have to eat as much. They have no stomach.
# Body covering
The only modern Agnathan body covering is skin. There are no scales. Extinct Agnathans had thick body plates (see below).
# Appendages
Agnathans have no paired appendages, although they do have a tail and a caudal fin.
# Skeleton
The internal skeleton of the Agnatha is not bony but rather cartilaginous (made up of dense connective tissue). Also, Agnathans have a notochord their whole life, a characteristic distinctive of the class. This notochord is the first primitive vertebral column.
# Reproduction
Fertilization is external, as is development. There is no parental care.
# Fossil agnathans
Although a minor element of modern marine fauna, Agnatha were prominent among the early fish in the early Paleozoic. Two types of Early Cambrian animal apparently having fins, vertebrate musculature, and gills are known from the early Cambrian Maotianshan shales of China: Haikouichthys and Myllokunmingia. They have been tentatively assigned to Agnatha by Janvier. A third possible agnathid from the same region is Haikouella. A possible agnathid that has not been formally described was reported by Simonetti from the Middle Cambrian Burgess Shale of British Columbia.
Many Ordovician, Silurian, and Devonian agnathans were armored with heavy bony-spiky plates. The first armored agnathans—the Ostracoderms, precursors to the bony fish and hence to the tetrapods (including humans)—are known from the middle Ordovician, and by the Late Silurian the agnathans had reached the high point of their evolution. Agnathans declined in the Devonian and never recovered.
# Groups
- Myxini (hagfish)
- Hyperoartia
Petromyzontidae (lampreys)
- Petromyzontidae (lampreys)
- Pteraspidomorphi
- Thelodonti
- Anaspida
- Cephalaspidomorphi
Galeaspida
Pituriaspida
Osteostraci
- Galeaspida
- Pituriaspida
- Osteostraci | Agnatha
Agnatha (Greek, "no jaws") is a paraphyletic[1] superclass of jawless fish in the phylum Chordata, subphylum Vertebrata. It has existed since the Cambrian, and continues to live now. There are two extant groups of jawless fish (sometimes called cyclostomes), the lampreys and the hagfish, with about 100 species in total. Although they are in the subphylum Vertebrata, hagfish technically do not have vertebrae; they are sometimes classified in Craniata. In addition to the absence of jaws, Agnatha are characterised by absence of paired fins; the presence of a notochord both in larvae and adults; and seven or more paired gill pouches. There is a light sensitive pineal eye (homologous to the pineal gland in mammals). All living and most extinct Agnatha do not have an identifiable stomach or any appendages. Fertilization and development are both external. There is no parental care in the Agnatha class. The Agnatha are ectothermic, with a cartilaginous skeleton, and the heart contains 2 chambers.
Although they are superficially similar, many of these similarities are probably shared basal characteristics of ancient vertebrates, and modern classifications tend to place hagfish into a separate group (the Myxini or Hyperotreti), with the lampreys (Hyperoartii) being more closely related to the jawed fishes.
# Respiratory system
Agnathans are characterized by seven or more pairs of gill pouches. The bronchial arches supporting the gill pouches lie close to the body surface.
# Metabolism
Agnathans are ectothermic or cold blooded, meaning they do not have to warm themselves through eating. Therefore, Agnathan metabolism is slow as well as the fact that Agnathans do not have to eat as much. They have no stomach.
# Body covering
The only modern Agnathan body covering is skin. There are no scales. Extinct Agnathans had thick body plates (see below).
# Appendages
Agnathans have no paired appendages, although they do have a tail and a caudal fin.
# Skeleton
The internal skeleton of the Agnatha is not bony but rather cartilaginous (made up of dense connective tissue). Also, Agnathans have a notochord their whole life, a characteristic distinctive of the class. This notochord is the first primitive vertebral column.
# Reproduction
Fertilization is external, as is development. There is no parental care.
# Fossil agnathans
Although a minor element of modern marine fauna, Agnatha were prominent among the early fish in the early Paleozoic. Two types of Early Cambrian animal apparently having fins, vertebrate musculature, and gills are known from the early Cambrian Maotianshan shales of China: Haikouichthys and Myllokunmingia. They have been tentatively assigned to Agnatha by Janvier. A third possible agnathid from the same region is Haikouella. A possible agnathid that has not been formally described was reported by Simonetti from the Middle Cambrian Burgess Shale of British Columbia.
Many Ordovician, Silurian, and Devonian agnathans were armored with heavy bony-spiky plates. The first armored agnathans—the Ostracoderms, precursors to the bony fish and hence to the tetrapods (including humans)—are known from the middle Ordovician, and by the Late Silurian the agnathans had reached the high point of their evolution. Agnathans declined in the Devonian and never recovered.
# Groups
- Myxini (hagfish)
- Hyperoartia
Petromyzontidae (lampreys)
- Petromyzontidae (lampreys)
- Pteraspidomorphi
- Thelodonti
- Anaspida
- Cephalaspidomorphi
Galeaspida
Pituriaspida
Osteostraci
- Galeaspida
- Pituriaspida
- Osteostraci | https://www.wikidoc.org/index.php/Agnatha | |
7cb3317c0365a5ad9c4cd109abe6de4b43f426ea | wikidoc | Agnosia | Agnosia
# Overview
Agnosia (a-gnosis, "non-knowledge", or loss of knowledge) is a loss of ability to recognize objects, persons, sounds, shapes, or smells while the specific sense is not defective nor is there any significant memory loss. It is usually associated with brain injury or neurological illness, particularly after damage to the temporal lobe.
# Historical Perspective
# Classification
## Types
- Visual agnosia is associated with lesions of the left occipital lobe and temporal lobes. Many are the inability to recognize objects. Subtypes:
Form agnosia: Patients perceive only parts of details, not the whole object.
Finger agnosia is the inability to distinguish the fingers on the hand. It is present in lesions of the dominant parietal lobe, and is a component of Gerstmann syndrome.
Simultanagnosia: Patients can recognize objects or details in their visual field, but only one at a time. They cannot make out the scene they belong to or make out a whole image out of the details. They literally cannot see the forest for the trees. Simultanagnosia is a common symptom of Balint's syndrome.
Associative agnosia: Patients can describe visual scenes and classes of objects but still fail to recognize them. He may, for example, know that a fork is something you eat with but may mistake it for a spoon. Patients suffering from associative agnosia are able to reproduce an image through copying.
Apperceptive agnosia: Patients are unable to distinguish visual shapes and so have trouble recognizing, copying, or discriminating between different visual stimuli. Unlike patients suffering from associative agnosia, those with apperceptive agnosia are unable to copy images.
Mirror agnosia: Patients cannot recognize objects or activity on either their left or right field of view. Impairment can vary from mild inattention to complete inability to perform spatial reasoning with regard to the afflicted side. The disorder takes its name from an experiment in which a patient was shown objects reflected in a mirror and saw them, but was unable to find them when prompted.
Semantic agnosia:
Agnosic alexia: Inability to recognize text.
Color agnosia: There is a distinction between color perception versus color recognition. Central achromatopsia and color blindness refer to deficiency in color perception.
Prosopagnosia also known as faceblindness and facial agnosia: Patients cannot consciously recognize familiar faces, sometimes even including their own. This is often misperceived as an inability to remember names. People with PA frequently (but not always) also suffer from topographical agnosia (poor sense of direction, get lost easily), automobilia agnosia (an inability to recognize cars), expressive agnosia (an inability to perceive people's moods from their facial expressions), verbal agnosia (see below) and possibly dyscalculia (poor with numbers).
- Form agnosia: Patients perceive only parts of details, not the whole object.
- Finger agnosia is the inability to distinguish the fingers on the hand. It is present in lesions of the dominant parietal lobe, and is a component of Gerstmann syndrome.
- Simultanagnosia: Patients can recognize objects or details in their visual field, but only one at a time. They cannot make out the scene they belong to or make out a whole image out of the details. They literally cannot see the forest for the trees. Simultanagnosia is a common symptom of Balint's syndrome.
- Associative agnosia: Patients can describe visual scenes and classes of objects but still fail to recognize them. He may, for example, know that a fork is something you eat with but may mistake it for a spoon. Patients suffering from associative agnosia are able to reproduce an image through copying.
- Apperceptive agnosia: Patients are unable to distinguish visual shapes and so have trouble recognizing, copying, or discriminating between different visual stimuli. Unlike patients suffering from associative agnosia, those with apperceptive agnosia are unable to copy images.
- Mirror agnosia: Patients cannot recognize objects or activity on either their left or right field of view. Impairment can vary from mild inattention to complete inability to perform spatial reasoning with regard to the afflicted side. The disorder takes its name from an experiment in which a patient was shown objects reflected in a mirror and saw them, but was unable to find them when prompted.
- Semantic agnosia:
- Agnosic alexia: Inability to recognize text.
- Color agnosia: There is a distinction between color perception versus color recognition. Central achromatopsia and color blindness refer to deficiency in color perception.
- Prosopagnosia also known as faceblindness and facial agnosia: Patients cannot consciously recognize familiar faces, sometimes even including their own. This is often misperceived as an inability to remember names. People with PA frequently (but not always) also suffer from topographical agnosia (poor sense of direction, get lost easily), automobilia agnosia (an inability to recognize cars), expressive agnosia (an inability to perceive people's moods from their facial expressions), verbal agnosia (see below) and possibly dyscalculia (poor with numbers).
- Auditory agnosia refers to similar symptoms for sounds. This term is sometimes used with the limited reference to environmental, nonverbal auditory cues, as separate from verbal agnosia There is a weakly defined link between these terms and CAPD/APD (originally Central Auditory Processing Disorder, the term Auditory Processing Disorder is now preferred).
Verbal auditory agnosia or Pure word deafness or simply word deafness: agnosia connected to verbal information. Patients may hear the sounds of the words, but they don't understand what they mean or can't recognize them as words.
Amusia or Receptive amusia is agnosia for music. It involves loss of the ability to recognize musical notes, rhythms, and intervals and the inability to experience music as musical.
Cortical deafness refers to people who do not respond to any auditory information but whose hearing is intact.
Phonagnosia is the inability to recognize familiar voices, even though the hearer can understand the words used.
- Verbal auditory agnosia or Pure word deafness or simply word deafness: agnosia connected to verbal information. Patients may hear the sounds of the words, but they don't understand what they mean or can't recognize them as words.
- Amusia or Receptive amusia is agnosia for music. It involves loss of the ability to recognize musical notes, rhythms, and intervals and the inability to experience music as musical.
- Cortical deafness refers to people who do not respond to any auditory information but whose hearing is intact.
- Phonagnosia is the inability to recognize familiar voices, even though the hearer can understand the words used.
- Somatosensory agnosia or Astereognosia is connected to tactile sense - that is, touch. Patient finds it difficult to recognize objects by touch based on its texture, size and weight. However, they may be able to describe it verbally or recognize same kind of objects from pictures or draw pictures of them. Thought to be connected to lesions or damage in somatosensory cortex.
# Pathophysiology
# Causes
Agnosia can result from strokes, dementia, or other neurological disorders. It may also be trauma-induced by a head injury, or hereditary. Until the 1990s, it was not believed to be genetic, but that view has changed.
# Differentiating Agnosia from Other Diseases
# Epidemiology and Demographics
# Risk Factors
# Screening
# Natural History, Complications, and Prognosis
# Diagnosis
## Diagnostic Criteria
## History and Symptoms
## Physical Examination
## Laboratory Findings
## Imaging Findings
## Other Diagnostic Studies
# Treatment
For all practical purposes, there is no direct cure. Patients may improve if information is presented in other modalities than the damaged one. In some cases, occupational therapy or speech therapy can improve agnosia, depending on its etiology.
## Medical Therapy
## Surgery
## Prevention | Agnosia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Template:DiseaseDisorder infobox
# Overview
Agnosia (a-gnosis, "non-knowledge", or loss of knowledge) is a loss of ability to recognize objects, persons, sounds, shapes, or smells while the specific sense is not defective nor is there any significant memory loss. It is usually associated with brain injury or neurological illness, particularly after damage to the temporal lobe.
# Historical Perspective
# Classification
## Types
- Visual agnosia is associated with lesions of the left occipital lobe and temporal lobes. Many are the inability to recognize objects. Subtypes:
Form agnosia: Patients perceive only parts of details, not the whole object.
Finger agnosia is the inability to distinguish the fingers on the hand. It is present in lesions of the dominant parietal lobe, and is a component of Gerstmann syndrome.
Simultanagnosia: Patients can recognize objects or details in their visual field, but only one at a time. They cannot make out the scene they belong to or make out a whole image out of the details. They literally cannot see the forest for the trees. Simultanagnosia is a common symptom of Balint's syndrome.
Associative agnosia: Patients can describe visual scenes and classes of objects but still fail to recognize them. He may, for example, know that a fork is something you eat with but may mistake it for a spoon. Patients suffering from associative agnosia are able to reproduce an image through copying.
Apperceptive agnosia: Patients are unable to distinguish visual shapes and so have trouble recognizing, copying, or discriminating between different visual stimuli. Unlike patients suffering from associative agnosia, those with apperceptive agnosia are unable to copy images.
Mirror agnosia: Patients cannot recognize objects or activity on either their left or right field of view. Impairment can vary from mild inattention to complete inability to perform spatial reasoning with regard to the afflicted side. The disorder takes its name from an experiment in which a patient was shown objects reflected in a mirror and saw them, but was unable to find them when prompted.
Semantic agnosia:
Agnosic alexia: Inability to recognize text.
Color agnosia: There is a distinction between color perception versus color recognition. Central achromatopsia and color blindness refer to deficiency in color perception.
Prosopagnosia also known as faceblindness and facial agnosia: Patients cannot consciously recognize familiar faces, sometimes even including their own. This is often misperceived as an inability to remember names. People with PA frequently (but not always) also suffer from topographical agnosia (poor sense of direction, get lost easily), automobilia agnosia (an inability to recognize cars), expressive agnosia (an inability to perceive people's moods from their facial expressions), verbal agnosia (see below) and possibly dyscalculia (poor with numbers).
- Form agnosia: Patients perceive only parts of details, not the whole object.
- Finger agnosia is the inability to distinguish the fingers on the hand. It is present in lesions of the dominant parietal lobe, and is a component of Gerstmann syndrome.
- Simultanagnosia: Patients can recognize objects or details in their visual field, but only one at a time. They cannot make out the scene they belong to or make out a whole image out of the details. They literally cannot see the forest for the trees. Simultanagnosia is a common symptom of Balint's syndrome.
- Associative agnosia: Patients can describe visual scenes and classes of objects but still fail to recognize them. He may, for example, know that a fork is something you eat with but may mistake it for a spoon. Patients suffering from associative agnosia are able to reproduce an image through copying.
- Apperceptive agnosia: Patients are unable to distinguish visual shapes and so have trouble recognizing, copying, or discriminating between different visual stimuli. Unlike patients suffering from associative agnosia, those with apperceptive agnosia are unable to copy images.
- Mirror agnosia: Patients cannot recognize objects or activity on either their left or right field of view. Impairment can vary from mild inattention to complete inability to perform spatial reasoning with regard to the afflicted side. The disorder takes its name from an experiment in which a patient was shown objects reflected in a mirror and saw them, but was unable to find them when prompted.
- Semantic agnosia:
- Agnosic alexia: Inability to recognize text.
- Color agnosia: There is a distinction between color perception versus color recognition. Central achromatopsia and color blindness refer to deficiency in color perception.
- Prosopagnosia also known as faceblindness and facial agnosia: Patients cannot consciously recognize familiar faces, sometimes even including their own. This is often misperceived as an inability to remember names. People with PA frequently (but not always) also suffer from topographical agnosia (poor sense of direction, get lost easily), automobilia agnosia (an inability to recognize cars), expressive agnosia (an inability to perceive people's moods from their facial expressions), verbal agnosia (see below) and possibly dyscalculia (poor with numbers).
- Auditory agnosia refers to similar symptoms for sounds. This term is sometimes used with the limited reference to environmental, nonverbal auditory cues, as separate from verbal agnosia There is a weakly defined link between these terms and CAPD/APD (originally Central Auditory Processing Disorder, the term Auditory Processing Disorder is now preferred).
Verbal auditory agnosia or Pure word deafness or simply word deafness: agnosia connected to verbal information. Patients may hear the sounds of the words, but they don't understand what they mean or can't recognize them as words.
Amusia or Receptive amusia is agnosia for music. It involves loss of the ability to recognize musical notes, rhythms, and intervals and the inability to experience music as musical.
Cortical deafness refers to people who do not respond to any auditory information but whose hearing is intact.
Phonagnosia is the inability to recognize familiar voices, even though the hearer can understand the words used.
- Verbal auditory agnosia or Pure word deafness or simply word deafness: agnosia connected to verbal information. Patients may hear the sounds of the words, but they don't understand what they mean or can't recognize them as words.
- Amusia or Receptive amusia is agnosia for music. It involves loss of the ability to recognize musical notes, rhythms, and intervals and the inability to experience music as musical.
- Cortical deafness refers to people who do not respond to any auditory information but whose hearing is intact.
- Phonagnosia is the inability to recognize familiar voices, even though the hearer can understand the words used.
- Somatosensory agnosia or Astereognosia is connected to tactile sense - that is, touch. Patient finds it difficult to recognize objects by touch based on its texture, size and weight. However, they may be able to describe it verbally or recognize same kind of objects from pictures or draw pictures of them. Thought to be connected to lesions or damage in somatosensory cortex.
# Pathophysiology
# Causes
Agnosia can result from strokes, dementia, or other neurological disorders. It may also be trauma-induced by a head injury, or hereditary. Until the 1990s, it was not believed to be genetic, but that view has changed.
# Differentiating Agnosia from Other Diseases
# Epidemiology and Demographics
# Risk Factors
# Screening
# Natural History, Complications, and Prognosis
# Diagnosis
## Diagnostic Criteria
## History and Symptoms
## Physical Examination
## Laboratory Findings
## Imaging Findings
## Other Diagnostic Studies
# Treatment
For all practical purposes, there is no direct cure. Patients may improve if information is presented in other modalities than the damaged one. In some cases, occupational therapy or speech therapy can improve agnosia, depending on its etiology.
## Medical Therapy
## Surgery
## Prevention | https://www.wikidoc.org/index.php/Agnosia | |
9035afcef424582ec11f7e4e1511bd52e245921a | wikidoc | Agonist | Agonist
In pharmacology an agonist is a substance that binds to a specific receptor and triggers a response in the cell. It mimics the action of an endogenous ligand (such as hormone or neurotransmitter) that binds to the same receptor.
# Types
Full agonists bind (have affinity for) and activate a receptor, displaying full efficacy at that receptor.
One example of a drug that acts as a full agonist is isoproterenol which mimics the action of adrenaline at β adrenoreceptors.
Partial agonists (such as buspirone, aripiprazole, buprenorphine, or norclozapine) also bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic effects - when both a full agonist and partial agonist are present, the partial agonist actually acts as a competitive antagonist, competing with the full agonist for receptor occupancy and producing a net decrease in the receptor activation observed with the full agonist alone.
A co-agonist works with other co-agonists to produce the desired effect together. NMDA receptor activation requires the binding of both of its glutamate and glycine co-agonists. An antagonist blocks a receptor from activation by agonists. Clinically partial agonists can activate receptors to give a desired submaximal response when inadequate amounts of the endogenous ligand are present, or they can reduce the overstimulation of receptors when excess amounts of the endogenous ligand are present.
A selective agonist is selective for one certain type of receptor. It can additionally be of any of the aforementioned types.
A physiological agonist is a substance that creates the same bodily responses, but does not bind to the same receptor.
Receptors can be activated or inactivated either by endogenous (such as hormones and neurotransmitters) or exogenous (such as drugs) agonists and antagonists, resulting in stimulating or inhibiting a biological response. To see how an agonist may activate a receptor see this link
New findings that broaden the conventional definition of pharmacology demonstrate that ligands can concurrently behave as agonist and antagonists at the same receptor, depending on effector pathways. Terms that describe this phenomenon are "functional selectivity" or "protean agonism".
# Activity (EC50)
## Potency
The potency of an agonist is usually defined by its EC50 value. This can be calculated for a given agonist by determining the concentration of agonist needed to elicit half of the maximum biological response of the agonist. Elucidating an EC50 value is useful for comparing the potency of drugs with similar efficacies producing physiologically similar effects. The lower the EC50, the greater the potency of the agonist the lower the concentration of drug that is required to elicit the maximum biological response
## Therapeutic index
When a drug is used therapeutically, it is important to understand the margin of safety that exists between the dose needed for the desired effect and the dose that produces unwanted and possibly dangerous side effects. This relationship, termed the therapeutic index, is defined as the ratio LD50:ED50. In general, the narrower this margin, the more likely it is that the drug will produce unwanted effects. The therapeutic index has many limitations, notably the fact that LD50 cannot be measured in humans and, when measured in animals, is a poor guide to the likelihood of unwanted effects in humans. Nevertheless, the therapeutic index emphasizes the importance of the margin of safety, as distinct from the potency, in determining the usefulness of a drug.
# Etymology
From the Greek αγωνιστής (agōnistēs), contestant; champion; rival < αγων (agōn), contest, combat; exertion, struggle < αγω (agō), I lead, lead towards, conduct; drive | Agonist
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
In pharmacology an agonist is a substance that binds to a specific receptor and triggers a response in the cell. It mimics the action of an endogenous ligand (such as hormone or neurotransmitter) that binds to the same receptor.
# Types
Full agonists bind (have affinity for) and activate a receptor, displaying full efficacy at that receptor.
One example of a drug that acts as a full agonist is isoproterenol which mimics the action of adrenaline at β adrenoreceptors.
Partial agonists (such as buspirone, aripiprazole, buprenorphine, or norclozapine) also bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic effects - when both a full agonist and partial agonist are present, the partial agonist actually acts as a competitive antagonist, competing with the full agonist for receptor occupancy and producing a net decrease in the receptor activation observed with the full agonist alone.[1]
A co-agonist works with other co-agonists to produce the desired effect together. NMDA receptor activation requires the binding of both of its glutamate and glycine co-agonists. An antagonist blocks a receptor from activation by agonists. Clinically partial agonists can activate receptors to give a desired submaximal response when inadequate amounts of the endogenous ligand are present, or they can reduce the overstimulation of receptors when excess amounts of the endogenous ligand are present.[2]
A selective agonist is selective for one certain type of receptor. It can additionally be of any of the aforementioned types.
A physiological agonist is a substance that creates the same bodily responses, but does not bind to the same receptor.
Receptors can be activated or inactivated either by endogenous (such as hormones and neurotransmitters) or exogenous (such as drugs) agonists and antagonists, resulting in stimulating or inhibiting a biological response. To see how an agonist may activate a receptor see this link
New findings that broaden the conventional definition of pharmacology demonstrate that ligands can concurrently behave as agonist and antagonists at the same receptor, depending on effector pathways. Terms that describe this phenomenon are "functional selectivity" or "protean agonism".[3][4]
# Activity (EC50)
## Potency
The potency of an agonist is usually defined by its EC50 value. This can be calculated for a given agonist by determining the concentration of agonist needed to elicit half of the maximum biological response of the agonist. Elucidating an EC50 value is useful for comparing the potency of drugs with similar efficacies producing physiologically similar effects. The lower the EC50, the greater the potency of the agonist the lower the concentration of drug that is required to elicit the maximum biological response
## Therapeutic index
When a drug is used therapeutically, it is important to understand the margin of safety that exists between the dose needed for the desired effect and the dose that produces unwanted and possibly dangerous side effects. This relationship, termed the therapeutic index, is defined as the ratio LD50:ED50. In general, the narrower this margin, the more likely it is that the drug will produce unwanted effects. The therapeutic index has many limitations, notably the fact that LD50 cannot be measured in humans and, when measured in animals, is a poor guide to the likelihood of unwanted effects in humans. Nevertheless, the therapeutic index emphasizes the importance of the margin of safety, as distinct from the potency, in determining the usefulness of a drug.
# Etymology
From the Greek αγωνιστής (agōnistēs), contestant; champion; rival < αγων (agōn), contest, combat; exertion, struggle < αγω (agō), I lead, lead towards, conduct; drive | https://www.wikidoc.org/index.php/Agonist | |
68228a444b2e4634361cb0143d036546c34d1ea9 | wikidoc | Disease | Disease
# Overview
A disease is an abnormal condition of an organism that impairs bodily functions. In human beings, "disease" is often used more broadly to refer to any condition that causes discomfort, dysfunction, distress, social problems, and/or death to the person afflicted, or similar problems for those in contact with the person. In this broader sense, it sometimes includes injuries, disabilities, disorders, syndromes, infections, isolated symptoms, deviant behaviors, and atypical variations of structure and function, while in other contexts and for other purposes these may be considered distinguishable categories.
While many diseases are biological processes with observable alterations of organ function or structure, others primarily involve alterations of behavior.
Classifying a condition as a disease is a social act of valuation, and may change the social status of the person with the condition (the patient). Some conditions (known as culture-bound syndromes) are only recognized as diseases within a particular culture. Sometimes the categorization of a condition as a disease is controversial within the culture.
# Causes of disease
Many different factors intrinsic or extrinsic to a person (or plant or animal) can cause disease. Examples of intrinsic factors are genetic defects or nutritional deficiencies. An environmental exposure, such as second-hand smoke is an example of an extrinsic factor. Many diseases result from a combination of intrinsic and extrinsic factors. For many diseases a cause cannot be identified.
There are many different factors that can cause disease. These can be broadly categorized into the following categories like social, psychological, chemical and biological. Some factors may fall into more than one category. Biochemical causes of disease can be considered as a spectrum where at one extreme disease is caused entirely by genetic factors (e.g. CAG repeats in the Huntingtin gene that causes Huntington's Disease) and at the other extreme is caused entirely by environmental factors. Environmental factors include toxic chemicals (e.g. acetaldehyde in cigarette smoke and dioxins released from the breakdown of Agent Orange) and infectious agents (e.g. smallpox virus and poliovirus). In between these extremes genes (e.g. NOD2/CARD15) and environmental factors (e.g. Gut microbiota) interact to cause disease, as seen for example in the inflammatory bowel disease Crohn's Disease (Fig 1, right).
Absence of the genetic or environmental factors in this case results in disease not being manifest. Koch's postulates can be used to determine whether a disease is caused by an infectious agent.
To determine whether a disease is caused by genetic factors, researchers study the pattern inheritance of the disease in families. This provides qualitative information about the disease (how it is inherited). A classic example of this method of research is inheritance of hemophilia in the British Royal Family. More recently this research has been used to identify the Apoliprotein E (ApoE) gene as a susceptibility gene for Alzheimer's Disease, though some forms of this gene - ApoE2 - are associated with a lower susceptibility. To determine to what extent a disease is caused by genetic factors (quantitative information), twin studies are used. Monozygotic twins are genetically identical and likely share a similar environment whereas dizygotic twins are genetically similar and likely share a similar environment. Thus by comparing the incidence of disease (termed concordance rate) in monozygotic twins with the incidence of disease in dizygotic twins, the extent to which genes contribute to disease can be determined. Candidate disease genes can be identified using a number of methods. One is to look for mutants of a model organism (e.g. the organisms Mus musculus,Drosophila melanogaster, Caenhorhabditis elegans,Brachydanio rerio and Xenopus tropicalis) that have a similar phenotype to the disease being studied. Another approach is to look for segregation of genes or genetic markers (e.g. single nucleotide polymorphism or expressed sequence tag) (Fig. 2).
A large number of SNPs spaced throughout the genome have been identified recently in a large project called the HapMap project). The usefulness of the HapMap project and SNP typing and their relevance to society was covered in the 27 October 2005 issue of the leading international science journal Nature (journal).
A large number of genes have been identified that contribute to human disease. These are available from the US National Library of Medicine, which has an impressive range of biological science resources available for free online. Amongst these resources is Online Mendelian Inheritance in Man - OMIM that provides a very, very comprehensive list of all known human gene mutations associated with, and likely contributing to, disease. Each article at OMIM is regularly updated to include the latest scientific research. Additionally, each article provides a detailed history of the research on a given disease gene, with links to the research articles. This resource is highly valuable and is used by the world's top science researchers.
# Related concepts
The terms disease, disorder, medical condition are often used interchangeably. There is no agreed-upon universal distinction between these terms, though some people do make distinctions in particular contexts.
Medical usage sometimes distinguishes a disease, which has a known specific cause or causes (called its etiology), from a syndrome, which is a collection of signs or symptoms that occur together. However, many conditions have been identified, yet continue to be referred to as "syndromes." Furthermore, numerous conditions of unknown etiology are referred to as "diseases" in many contexts. Refractory diseases do not respond to therapy by overcoming the resistance to drugs.
Illness, although often used to mean disease, can also refer to a person's perception of their health, regardless of whether they in fact have a disease. A person without any disease may feel unhealthy and simply have the perception of having an illness. Another person may feel healthy with similar perceptions of perfectly good health. The individual's perception of good health may even persist with the medical diagnosis of having a disease; for example, such as dangerously high blood pressure, which may lead to a fatal heart attack or stroke.
Pathology is the study of diseases. The subject of systematic classification of diseases is referred to as nosology. Its cause is referred as its etiology. The broader body of knowledge about human diseases and their treatments is medicine. Many similar (and a few of the same) conditions or processes can affect non-human animals (wild or domestic). The study of diseases affecting animals is veterinary medicine.
Disease can be thought of as the presence of pathology, which can occur with or without subjective feelings of being unwell or social recognition of that state. Illness as the subjective state of "unwellness" can occur independently of, or in conjunction with, disease or sickness (with sickness the social classification of someone deemed diseased, which can also occur independently of the presence or absence of disease or illness (c.f. subjective medical conditions). Thus, someone with undetected high blood pressure who feels to be of good health would be diseased, but not ill or sick. Someone with a diagnosis of late-stage cancer would be diseased, probably feeling quite ill, and recognized by others as sick. A person incarcerated in a totalitarian psychiatric hospital for political purposes could arguably be then said to not be diseased, nor ill, but only classified as sick by the rulers of a society with which the person did not agree. Having had a bad day after a night of excess drinking, one might feel ill, but one would not be diseased, nor is it likely that a boss could be convinced of the sickness.
# Transmission of disease
Some diseases such as influenza are contagious or infectious. Infectious diseases can be transmitted by any of a variety of mechanisms, including aerosols produced by coughs and sneezes, by bites of insects or other carriers of the disease, and from contaminated water or food (possibly by faeces or urine in the sewage), etc. Also, there are sexually transmitted diseases. When micro-organisms that cannot be spread from person to person might play a role, some diseases can be prevented with proper nutrition. Other diseases such as cancer and heart disease are not considered to be caused by infection. The same is true of mental diseases.
# Social significance of disease
Living with disease can be very difficult. The identification of a condition as a disease, rather than as simply a variation of human structure or function, can have significant social or economic implications. The controversial recognitions as diseases of post-traumatic stress disorder, also known as "Soldier's heart," "shell shock," and "combat fatigue;" repetitive motion injury or repetitive stress injury (RSI); and Gulf War syndrome has had a number of positive and negative effects on the financial and other responsibilities of governments, corporations and institutions towards individuals, as well as on the individuals themselves. The social implication of viewing aging as a disease could be profound, though this classification is not yet widespread.
A condition may be considered to be a disease in some cultures or eras but not in others. Oppositional-defiant disorder, attention-deficit hyperactivity disorder, and, increasingly, obesity, are conditions considered to be diseases in the United States and Canada today, but were not so-considered decades ago and are not so-considered in some other countries. Lepers were a group of afflicted individuals who were historically shunned and the term "leper" still evokes social stigma. Fear of disease can still be a widespread social phenomena, though not all diseases evoke extreme social stigma.
Sickness confers the social legitimization of certain benefits, such as illness benefits, work avoidance, and being looked after by others. In return, there is an obligation on the sick person to seek treatment and work to become well once more. As a comparison, consider pregnancy, which is not a state interpreted as disease or sickness by the individual. On the other hand, it is considered by the medical community as a condition requiring medical care and by society at large as a condition requiring one's staying at home from work.
# Global Disease Burden
This chart, compiled in 2002 from the World Health Organization's Global Burden of Disease shows an overview of the impact of various classifications of disease, segregated by regions with low and high mortality: | Disease
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
A disease is an abnormal condition of an organism that impairs bodily functions. In human beings, "disease" is often used more broadly to refer to any condition that causes discomfort, dysfunction, distress, social problems, and/or death to the person afflicted, or similar problems for those in contact with the person. In this broader sense, it sometimes includes injuries, disabilities, disorders, syndromes, infections, isolated symptoms, deviant behaviors, and atypical variations of structure and function, while in other contexts and for other purposes these may be considered distinguishable categories.
While many diseases are biological processes with observable alterations of organ function or structure, others primarily involve alterations of behavior.
Classifying a condition as a disease is a social act of valuation, and may change the social status of the person with the condition (the patient). Some conditions (known as culture-bound syndromes) are only recognized as diseases within a particular culture. Sometimes the categorization of a condition as a disease is controversial within the culture.
# Causes of disease
Many different factors intrinsic or extrinsic to a person (or plant or animal) can cause disease. Examples of intrinsic factors are genetic defects or nutritional deficiencies. An environmental exposure, such as second-hand smoke is an example of an extrinsic factor. Many diseases result from a combination of intrinsic and extrinsic factors. For many diseases a cause cannot be identified.
There are many different factors that can cause disease. These can be broadly categorized into the following categories like social, psychological, chemical and biological. Some factors may fall into more than one category. Biochemical causes of disease can be considered as a spectrum where at one extreme disease is caused entirely by genetic factors (e.g. CAG repeats in the Huntingtin gene that causes Huntington's Disease) and at the other extreme is caused entirely by environmental factors. Environmental factors include toxic chemicals (e.g. acetaldehyde in cigarette smoke and dioxins released from the breakdown of Agent Orange) and infectious agents (e.g. smallpox virus and poliovirus). In between these extremes genes (e.g. NOD2/CARD15) and environmental factors (e.g. Gut microbiota) interact to cause disease, as seen for example in the inflammatory bowel disease Crohn's Disease (Fig 1, right).
Absence of the genetic or environmental factors in this case results in disease not being manifest. Koch's postulates can be used to determine whether a disease is caused by an infectious agent.
To determine whether a disease is caused by genetic factors, researchers study the pattern inheritance of the disease in families. This provides qualitative information about the disease (how it is inherited). A classic example of this method of research is inheritance of hemophilia in the British Royal Family. More recently this research has been used to identify the Apoliprotein E (ApoE) gene as a susceptibility gene for Alzheimer's Disease, though some forms of this gene - ApoE2 - are associated with a lower susceptibility. To determine to what extent a disease is caused by genetic factors (quantitative information), twin studies are used. Monozygotic twins are genetically identical and likely share a similar environment whereas dizygotic twins are genetically similar and likely share a similar environment. Thus by comparing the incidence of disease (termed concordance rate) in monozygotic twins with the incidence of disease in dizygotic twins, the extent to which genes contribute to disease can be determined. Candidate disease genes can be identified using a number of methods. One is to look for mutants of a model organism (e.g. the organisms Mus musculus,Drosophila melanogaster, Caenhorhabditis elegans,Brachydanio rerio and Xenopus tropicalis) that have a similar phenotype to the disease being studied. Another approach is to look for segregation of genes or genetic markers (e.g. single nucleotide polymorphism or expressed sequence tag) (Fig. 2).
A large number of SNPs spaced throughout the genome have been identified recently in a large project called the HapMap project[1][2]). The usefulness of the HapMap project and SNP typing and their relevance to society was covered in the 27 October 2005 issue of the leading international science journal Nature (journal).
A large number of genes have been identified that contribute to human disease. These are available from the US National Library of Medicine, which has an impressive range of biological science resources available for free online. Amongst these resources is Online Mendelian Inheritance in Man - OMIM that provides a very, very comprehensive list of all known human gene mutations associated with, and likely contributing to, disease. Each article at OMIM is regularly updated to include the latest scientific research. Additionally, each article provides a detailed history of the research on a given disease gene, with links to the research articles. This resource is highly valuable and is used by the world's top science researchers.
# Related concepts
The terms disease, disorder, medical condition are often used interchangeably. There is no agreed-upon universal distinction between these terms, though some people do make distinctions in particular contexts.
Medical usage sometimes distinguishes a disease, which has a known specific cause or causes (called its etiology), from a syndrome, which is a collection of signs or symptoms that occur together. However, many conditions have been identified, yet continue to be referred to as "syndromes." Furthermore, numerous conditions of unknown etiology are referred to as "diseases" in many contexts. Refractory diseases do not respond to therapy by overcoming the resistance to drugs.
Illness, although often used to mean disease, can also refer to a person's perception of their health, regardless of whether they in fact have a disease. A person without any disease may feel unhealthy and simply have the perception of having an illness. Another person may feel healthy with similar perceptions of perfectly good health. The individual's perception of good health may even persist with the medical diagnosis of having a disease; for example, such as dangerously high blood pressure, which may lead to a fatal heart attack or stroke.
Pathology is the study of diseases. The subject of systematic classification of diseases is referred to as nosology. Its cause is referred as its etiology. The broader body of knowledge about human diseases and their treatments is medicine. Many similar (and a few of the same) conditions or processes can affect non-human animals (wild or domestic). The study of diseases affecting animals is veterinary medicine.
Disease can be thought of as the presence of pathology, which can occur with or without subjective feelings of being unwell or social recognition of that state. Illness as the subjective state of "unwellness" can occur independently of, or in conjunction with, disease or sickness (with sickness the social classification of someone deemed diseased, which can also occur independently of the presence or absence of disease or illness (c.f. subjective medical conditions). Thus, someone with undetected high blood pressure who feels to be of good health would be diseased, but not ill or sick. Someone with a diagnosis of late-stage cancer would be diseased, probably feeling quite ill, and recognized by others as sick. A person incarcerated in a totalitarian psychiatric hospital for political purposes could arguably be then said to not be diseased, nor ill, but only classified as sick by the rulers of a society with which the person did not agree. Having had a bad day after a night of excess drinking, one might feel ill, but one would not be diseased, nor is it likely that a boss could be convinced of the sickness.
# Transmission of disease
Some diseases such as influenza are contagious or infectious. Infectious diseases can be transmitted by any of a variety of mechanisms, including aerosols produced by coughs and sneezes, by bites of insects or other carriers of the disease, and from contaminated water or food (possibly by faeces or urine in the sewage), etc. Also, there are sexually transmitted diseases. When micro-organisms that cannot be spread from person to person might play a role, some diseases can be prevented with proper nutrition. Other diseases such as cancer and heart disease are not considered to be caused by infection. The same is true of mental diseases.
# Social significance of disease
Living with disease can be very difficult. The identification of a condition as a disease, rather than as simply a variation of human structure or function, can have significant social or economic implications. The controversial recognitions as diseases of post-traumatic stress disorder, also known as "Soldier's heart," "shell shock," and "combat fatigue;" repetitive motion injury or repetitive stress injury (RSI); and Gulf War syndrome has had a number of positive and negative effects on the financial and other responsibilities of governments, corporations and institutions towards individuals, as well as on the individuals themselves. The social implication of viewing aging as a disease could be profound, though this classification is not yet widespread.
A condition may be considered to be a disease in some cultures or eras but not in others. Oppositional-defiant disorder, attention-deficit hyperactivity disorder, and, increasingly, obesity, are conditions considered to be diseases in the United States and Canada today, but were not so-considered decades ago and are not so-considered in some other countries. Lepers were a group of afflicted individuals who were historically shunned and the term "leper" still evokes social stigma. Fear of disease can still be a widespread social phenomena, though not all diseases evoke extreme social stigma.
Sickness confers the social legitimization of certain benefits, such as illness benefits, work avoidance, and being looked after by others. In return, there is an obligation on the sick person to seek treatment and work to become well once more. As a comparison, consider pregnancy, which is not a state interpreted as disease or sickness by the individual. On the other hand, it is considered by the medical community as a condition requiring medical care and by society at large as a condition requiring one's staying at home from work.
# Global Disease Burden
This chart, compiled in 2002 from the World Health Organization's Global Burden of Disease shows an overview of the impact of various classifications of disease, segregated by regions with low and high mortality: | https://www.wikidoc.org/index.php/Ailments | |
c9b78cb79969e23241420f17241ce03b3a2cad17 | wikidoc | Alanine | Alanine
Alanine (abbreviated as Ala or A) is an α-amino acid with the chemical formula HO2CCH(NH2)CH3. The L-isomer is one of the 20 proteinogenic amino acids, i.e. the building blocks of proteins. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid. L-alanine is second only to leucine, accounting for 7.8% of the primary structure in a sample of 1,150 proteins. D-alanine occurs in bacterial cell walls and in some peptide antibiotics.
# Structure
The α-carbon atom of alanine is bound with a methyl group (-CH3), making it one of the simplest α-amino acids with respect to molecular structure and also resulting in alanine being classified as an aliphatic amino acid. The methyl group of alanine is non-reactive and is thus almost never directly involved in protein function.
# Sources
## Dietary Sources
Alanine is a nonessential amino acid, meaning it can be manufactured by the human body, and does not need to be obtained directly through the diet. Alanine is found in a wide variety of foods, but is particularly concentrated in meats.
Good sources of alanine include:
- Animal souces: meat, seafood, caseinate, dairy products, eggs, fish, gelatin, lactalbumin
- Vegetarian sources: beans, nuts, seeds, soy, whey, brewer's yeast, brown rice bran, corn, legumes, whole grains.
## Biosynthesis
Alanine can be manufactured in the body from pyruvate and branched chain amino acids such as valine, leucine, and isoleucine.
Alanine is most commonly produced by reductive amination of pyruvate. Because transamination reactions are readily reversible and pyruvate pervasive, alanine can be easily formed and thus has close links to metabolic pathways such as glycolysis, gluconeogenesis, and the citric acid cycle. It also arises together with lactate and generate glucose from protein via the alanine cycle.
## Chemical Synthesis
Racemic alanine can be prepared via the addition of hydrogen cyanide and ammonia to acetaldehyde by the Strecker reaction.
# Physiological function
## As a carrier of ammonia and of the carbon skeleton of pyruvate in alanine cycle
Alanine plays a key role in glucose-alanine cycle between tissues and liver. In muscle and other tissues that degrade amino acids for fuel, amino groups are collected in the form of glutamate by transamination. Glutamate can then transfer its amino group through the action of alanine aminotransferase to pyruvate, a product of muscle glycolysis, forming alanine and alpha-ketoglutarate. The alanine formed is passed into the blood and transported to the liver. A reverse of the alanine aminotransferase reaction takes place in liver. Pyruvate regenerated forms glucose through gluconeogenesis, which returns to muscle through the circulation system. Glutamate in the liver enters mitochondria and degrades into ammonium ion through the action of glutamate dehydrogenase, which in turn participate in the urea cycle to form urea.
Glucose-alanine cycle enables pyruvate and glutamate to be removed from muscle and find their ways to liver. Glucose is able to be regenerated from pyruvate and returned muscle. The energetic burden of gluconeogenesis is thus imposed on the liver instead of the muscle. All available ATP in muscle is devoted to muscle contraction.
# Chemical Properties
## Free Radical Stability
One very unusual property of the alanine molecule is that it forms a stable free-radical. This phenomenon is surprising as free-radicals are typically a highly reactive species, and the reason for the stability of the alanine free-radical can not be derived from the fundamental principals of chemistry.
This property of alanine is used in dosimetric measurements in radiotherapy. When normal alanine is irradiated, the radiation causes certain alanine molecules to become free-radicals, and, as these radicals are stable, the free-radical content can later be measured in order to find out how much radiation the alanine was exposed to. In this way, one can be assured that complex radiotherapy treatment plans will deliver the intended pattern of radiation dose. | Alanine
Template:NatOrganicBox
Alanine (abbreviated as Ala or A)[1] is an α-amino acid with the chemical formula HO2CCH(NH2)CH3. The L-isomer is one of the 20 proteinogenic amino acids, i.e. the building blocks of proteins. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid. L-alanine is second only to leucine, accounting for 7.8% of the primary structure in a sample of 1,150 proteins.[2] D-alanine occurs in bacterial cell walls and in some peptide antibiotics.
# Structure
The α-carbon atom of alanine is bound with a methyl group (-CH3), making it one of the simplest α-amino acids with respect to molecular structure and also resulting in alanine being classified as an aliphatic amino acid. The methyl group of alanine is non-reactive and is thus almost never directly involved in protein function.
# Sources
## Dietary Sources
Alanine is a nonessential amino acid, meaning it can be manufactured by the human body, and does not need to be obtained directly through the diet. Alanine is found in a wide variety of foods, but is particularly concentrated in meats.
Good sources of alanine include:
- Animal souces: meat, seafood, caseinate, dairy products, eggs, fish, gelatin, lactalbumin
- Vegetarian sources: beans, nuts, seeds, soy, whey, brewer's yeast, brown rice bran, corn, legumes, whole grains.
## Biosynthesis
Alanine can be manufactured in the body from pyruvate and branched chain amino acids such as valine, leucine, and isoleucine.
Alanine is most commonly produced by reductive amination of pyruvate. Because transamination reactions are readily reversible and pyruvate pervasive, alanine can be easily formed and thus has close links to metabolic pathways such as glycolysis, gluconeogenesis, and the citric acid cycle. It also arises together with lactate and generate glucose from protein via the alanine cycle.
## Chemical Synthesis
Racemic alanine can be prepared via the addition of hydrogen cyanide and ammonia to acetaldehyde by the Strecker reaction.[3]
# Physiological function
## As a carrier of ammonia and of the carbon skeleton of pyruvate in alanine cycle
Alanine plays a key role in glucose-alanine cycle between tissues and liver. In muscle and other tissues that degrade amino acids for fuel, amino groups are collected in the form of glutamate by transamination. Glutamate can then transfer its amino group through the action of alanine aminotransferase to pyruvate, a product of muscle glycolysis, forming alanine and alpha-ketoglutarate. The alanine formed is passed into the blood and transported to the liver. A reverse of the alanine aminotransferase reaction takes place in liver. Pyruvate regenerated forms glucose through gluconeogenesis, which returns to muscle through the circulation system. Glutamate in the liver enters mitochondria and degrades into ammonium ion through the action of glutamate dehydrogenase, which in turn participate in the urea cycle to form urea.[4]
Glucose-alanine cycle enables pyruvate and glutamate to be removed from muscle and find their ways to liver. Glucose is able to be regenerated from pyruvate and returned muscle. The energetic burden of gluconeogenesis is thus imposed on the liver instead of the muscle. All available ATP in muscle is devoted to muscle contraction.[4]
# Chemical Properties
## Free Radical Stability
One very unusual property of the alanine molecule is that it forms a stable free-radical. This phenomenon is surprising as free-radicals are typically a highly reactive species, and the reason for the stability of the alanine free-radical can not be derived from the fundamental principals of chemistry.
This property of alanine is used in dosimetric measurements in radiotherapy. When normal alanine is irradiated, the radiation causes certain alanine molecules to become free-radicals, and, as these radicals are stable, the free-radical content can later be measured in order to find out how much radiation the alanine was exposed to. In this way, one can be assured that complex radiotherapy treatment plans will deliver the intended pattern of radiation dose. | https://www.wikidoc.org/index.php/Alanine | |
2cd12b845a534f6f92941b51f26ef73b6c0d2b79 | wikidoc | Albumin | Albumin
# 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
Albumin is a volume expander that is FDA approved for the treatment of hypovolemic shock, burn therapy, hypoproteinemia with or without edema, adult respiratory distress syndrome, acute liver failure, neonatal hemolytic disease, acute nephrosis. Common adverse reactions include hypersensitivity reaction.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
# Indications
Emergency Treatment of Hypovolemic Shock
- Albumin 20 is hyperoncotic and on intravenous infusion will expand the plasma volume by an additional amount, three to four times the volume actually administered, by withdrawing fluid from the interstitial spaces, provided the patient is normally hydrated interstitially or there is interstitial edema. If the patient is dehydrated, additional crystalloids must be given, or alternatively, Albumin (Human) 5%, USP (albumin™ 5) should be used. The patient’s hemodynamic response should be monitored and the usual precautions against circulatory overload observed. The total dose should not exceed the level of albumin found in the normal individual; i.e., about 2 g per kg body weight in the absence of active bleeding. Although albumin is to be preferred for the usual volume deficits, albumin 20 with appropriate crystalloids may offer therapeutic advantages in oncotic deficits or in long-standing shock where treatment has been delayed.
- Removal of ascitic fluid from a patient with cirrhosis may cause changes in cardiovascular function and even result in hypovolemic shock. In such circumstances, the use of an albumin infusion may be required to support the blood volume.
Burn Therapy
- An optimal therapeutic regimen with respect to the administration of colloids, crystalloids, and water following extensive burns has not been established. During the first 24 hours after sustaining thermal injury, large volumes of crystalloids are infused to restore the depleted extracellular fluid volume. Beyond 24 hours albumin 20 can be used to maintain plasma colloid osmotic pressure.
Hypoproteinemia With or Without Edema
- During major surgery, patients can lose over half of their circulating albumin with the attendant complications of oncotic deficit.A similar situation can occur in sepsis or intensive care patients. Treatment with albumin 20 may be of value in such cases.
Adult Respiratory Distress Syndrome (ARDS)
- This is characterized by deficient oxygenation caused by pulmonary interstitial edema complicating shock and postsurgical conditions. When clinical signs are those of hypoproteinemia with a fluid volume overload, albumin 20 together with a diuretic may play a role in therapy.
Cardiopulmonary Bypass
- With the relatively small priming volume required with modern pumps, preoperative dilution of the blood using albumin and crystalloid has been shown to be safe and well-tolerated. Although the limit to which the hematocrit and plasma protein concentration can be safely lowered has not been defined, it is common practice to adjust the albumin and crystalloid pump prime to achieve a hematocrit of 20% and a plasma albumin concentration of 2.5 g per 100 mL in the patient.
Acute Liver Failure
- In the uncommon situation of rapid loss of liver function with or without coma, administration of albumin may serve the double purpose of supporting the colloid osmotic pressure of the plasma as well as binding excess plasma bilirubin.
Neonatal Hemolytic Disease
- The administration of albumin 20 may be indicated prior to exchange transfusion, in order to bind free bilirubin, thus lessening the risk of kernicterus. A dosage of 1 g/kg body weight is given about 1 hour prior to exchange transfusion. Caution must be observed in hypervolemic infants.
Sequestration of Protein Rich Fluids
- This occurs in such conditions as acute peritonitis, pancreatitis, mediastinitis, and extensive cellulitis. The magnitude of loss into the third space may require treatment of reduced volume or oncotic activity with an infusion of albumin.
Erythrocyte Resuspension
- Albumin may be required to avoid excessive hypoproteinemia during certain types of exchange transfusion, or with the use of very large volumes of previously frozen or washed red cells. About 25 g of albumin per liter of erythrocytes is commonly used, although the requirements in preexistent hypoproteinemia or hepatic impairment can be greater. Albumin 20 is added to the isotonic suspension of washed red cells immediately prior to transfusion.
Acute Nephrosis
- Certain patients may not respond to cyclophosphamide or steroid therapy. The steroids may even aggravate the underlying edema. In this situation a loop diuretic and 100 mL albumin 20 repeated daily for 7 to 10 days may be helpful in controlling the edema and the patient may then respond to steroid treatment.
Renal Dialysis
- Although not part of the regular regimen of renal dialysis, albumin 20 may be of value in the treatment of shock or hypotension in these patients. The usual volume administered is about 100 mL, taking particular care to avoid fluid overload as these patients are often fluid overloaded and cannot tolerate substantial volumes of salt solution.
Situations in Which Albumin Administration is Not Warranted
- In chronic nephrosis, infused albumin is promptly excreted by the kidneys with no relief of the chronic edema or effect on the underlying renal lesion. It is of occasional use in the rapid “priming” diuresis of nephrosis. Similarly, in hypoproteinemic states associated with chronic cirrhosis, malabsorption, protein-losing enteropathies, pancreatic insufficiency, and undernutrition, the infusion of albumin as a source of protein nutrition is not justified.
# Dosage
Hypovolemic Shock — For treatment of hypovolemic shock, the volume administered and the speed of infusion should be adapted to the response of the individual patient.
Burns — After a burn injury (usually beyond 24 hours) there is a close correlation between the amount of albumin infused and the resultant increase in plasma colloid osmotic pressure. The aim should be to maintain the plasma albumin concentration in the region of 2.5 ± 0.5 g per 100 mL with a plasma oncotic pressure of 20 mm Hg (equivalent to a total plasma protein concentration of 5.2 g per 100 mL).(2) This is best achieved by the intravenous administration of albumin 20. The duration of therapy is decided by the loss of protein from the burned areas and in the urine. In addition, oral or parenteral feeding with amino acids should be initiated, as the long-term administration of albumin should not be considered as a source of nutrition.
Hypoproteinemia With or Without Edema — Unless the underlying pathology responsible for the hypoproteinemia can be corrected, the intravenous administration of albumin 20 must be considered purely symptomatic or supportive.The usual daily dose of albumin for adults is 50 to 75 g and for children 25 g. Patients with severe hypoproteinemia who continue to lose albumin may require larger quantities. Since hypoproteinemic patients usually have approximately normal blood volumes, the rate of administration of albumin 20 should not exceed 2 mL per minute, as more rapid injection may precipitate circulatory embarrassment and pulmonary edema.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Albumin in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Albumin in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Albumin in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Albumin in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Albumin in pediatric patients.
# Contraindications
- Certain patients, e.g., those with a history of congestive cardiac failure, renal insufficiency or stabilized chronic anemia, are at special risk of developing circulatory overload. A history of an allergic reaction to albumin is a specific contraindication to usage.
# Warnings
- Albumin (Human) 20%, USP (albumin™ 20) is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, and, theoretically, the Creutzfeldt-Jakob Disease (CJD) agent that can cause disease. The theoretical risk for transmission of CJD is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly hepatitis C. ALL infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Grifols Therapeutics Inc. .
- The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering it to the patient.
- As with any hyperoncotic protein solution likely to be administered in large volumes, severe hemolysis and acute renal failure may result from the inappropriate use of Sterile Water for Injection as a diluent for Albumin (Human), 20%. Acceptable diluents include 0.9% Sodium Chloride or 5% Dextrose in Water.
- Solutions which have been frozen should not be used. Do not use if turbid. Do not begin administration more than 4 hours after the container has been entered. Partially used vials must be discarded. Vials which are cracked or which have been previously entered or damaged should not be used, as this may have allowed the entry of microorganisms. Glbumin 20 contains no preservative.
# Adverse Reactions
## Clinical Trials Experience
- Adverse reactions to albumin are rare. Such reactions may be allergic in nature or due to high plasma protein levels from excessive albumin administration. Allergic manifestations include urticaria, chills, fever, and changes in respiration, pulse and blood pressure.
## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Albumin in the drug label.
# Drug Interactions
- Albumin 20 is compatible with whole blood, packed red cells, as well as the standard carbohydrate and electrolyte solutions intended for intravenous use. It should, however, not be mixed with protein hydrolysates, amino acid solutions nor those containing alcohol.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
Pregnancy Category C
- Animal reproduction studies have not been conducted with albumin 20. It is also not known whether albumin 20 can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Albumin 20 should be given to a pregnant woman only if clearly needed.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Albumin in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Albumin during labor and delivery.
### Nursing Mothers
There is no FDA guidance on the use of Albumin with respect to nursing mothers.
### Pediatric Use
- Safety and effectiveness in the pediatric population have not been established.
### Geriatic Use
There is no FDA guidance on the use of Albumin with respect to geriatric patients.
### Gender
There is no FDA guidance on the use of Albumin with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Albumin with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Albumin in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Albumin in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Albumin in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Albumin in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Intravenous
- Albumin 20 should always be administered by intravenous infusion. Albuked 20 may be administered either undiluted or diluted in 0.9% Sodium Chloride or 5% Dextrose in Water. If sodium restriction is required, Albuked 20 should only be administered either undiluted or diluted in a sodium-free carbohydrate solution such as 5% Dextrose in Water.
- A number of factors beyond our control could reduce the efficacy of this product or even result in an ill effect following its use. These include improper storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration, and biological differences in individual patients. Because of these factors, it is important that this product be stored properly and that the directions be followed carefully during use.
Preparation for Administration
- Remove seal to expose stopper. Always swab stopper top immediately with a suitable antiseptic prior to entering vial.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
- Only 16 gauge needles or dispensing pins should be used with 20 mL vial sizes and larger. Needles or dispensing pins should only be inserted within the stopper area delineated by the raised ring. The stopper should be penetrated perpendicular to the plane of the stopper within the ring.
### Monitoring
There is limited information regarding Monitoring of Albumin in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Albumin in the drug label.
# Overdosage
There is limited information regarding Chronic Overdose of Albumin in the drug label.
# Pharmacology
## Mechanism of Action
There is limited information regarding Albumin Mechanism of Action in the drug label.
## Structure
There is limited information regarding Albumin Structure in the drug label.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Albumin in the drug label.
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Albumin in the drug label.
## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Albumin in the drug label.
# Clinical Studies
There is limited information regarding Clinical Studies of Albumin in the drug label.
# How Supplied
- Albuked 20 is available in 50 mL and 100 mL rubber-stoppered vials. Each single dose vial contains albumin in the following approximate amounts:
## Storage
- Store at room temperature not exceeding 30°C (86°F). Do not freeze. Do not use after expiration date.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Albumin in the drug label.
# Precautions with Alcohol
- Alcohol-Albumin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- ALBUKED®
# Look-Alike Drug Names
- A® — B®
# Drug Shortage Status
# Price | Albumin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Albumin is a volume expander that is FDA approved for the treatment of hypovolemic shock, burn therapy, hypoproteinemia with or without edema, adult respiratory distress syndrome, acute liver failure, neonatal hemolytic disease, acute nephrosis. Common adverse reactions include hypersensitivity reaction.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
# Indications
Emergency Treatment of Hypovolemic Shock
- Albumin 20 is hyperoncotic and on intravenous infusion will expand the plasma volume by an additional amount, three to four times the volume actually administered, by withdrawing fluid from the interstitial spaces, provided the patient is normally hydrated interstitially or there is interstitial edema. If the patient is dehydrated, additional crystalloids must be given, or alternatively, Albumin (Human) 5%, USP (albumin™ 5) should be used. The patient’s hemodynamic response should be monitored and the usual precautions against circulatory overload observed. The total dose should not exceed the level of albumin found in the normal individual; i.e., about 2 g per kg body weight in the absence of active bleeding. Although albumin is to be preferred for the usual volume deficits, albumin 20 with appropriate crystalloids may offer therapeutic advantages in oncotic deficits or in long-standing shock where treatment has been delayed.
- Removal of ascitic fluid from a patient with cirrhosis may cause changes in cardiovascular function and even result in hypovolemic shock. In such circumstances, the use of an albumin infusion may be required to support the blood volume.
Burn Therapy
- An optimal therapeutic regimen with respect to the administration of colloids, crystalloids, and water following extensive burns has not been established. During the first 24 hours after sustaining thermal injury, large volumes of crystalloids are infused to restore the depleted extracellular fluid volume. Beyond 24 hours albumin 20 can be used to maintain plasma colloid osmotic pressure.
Hypoproteinemia With or Without Edema
- During major surgery, patients can lose over half of their circulating albumin with the attendant complications of oncotic deficit.A similar situation can occur in sepsis or intensive care patients. Treatment with albumin 20 may be of value in such cases.
Adult Respiratory Distress Syndrome (ARDS)
- This is characterized by deficient oxygenation caused by pulmonary interstitial edema complicating shock and postsurgical conditions. When clinical signs are those of hypoproteinemia with a fluid volume overload, albumin 20 together with a diuretic may play a role in therapy.
Cardiopulmonary Bypass
- With the relatively small priming volume required with modern pumps, preoperative dilution of the blood using albumin and crystalloid has been shown to be safe and well-tolerated. Although the limit to which the hematocrit and plasma protein concentration can be safely lowered has not been defined, it is common practice to adjust the albumin and crystalloid pump prime to achieve a hematocrit of 20% and a plasma albumin concentration of 2.5 g per 100 mL in the patient.
Acute Liver Failure
- In the uncommon situation of rapid loss of liver function with or without coma, administration of albumin may serve the double purpose of supporting the colloid osmotic pressure of the plasma as well as binding excess plasma bilirubin.
Neonatal Hemolytic Disease
- The administration of albumin 20 may be indicated prior to exchange transfusion, in order to bind free bilirubin, thus lessening the risk of kernicterus. A dosage of 1 g/kg body weight is given about 1 hour prior to exchange transfusion. Caution must be observed in hypervolemic infants.
Sequestration of Protein Rich Fluids
- This occurs in such conditions as acute peritonitis, pancreatitis, mediastinitis, and extensive cellulitis. The magnitude of loss into the third space may require treatment of reduced volume or oncotic activity with an infusion of albumin.
Erythrocyte Resuspension
- Albumin may be required to avoid excessive hypoproteinemia during certain types of exchange transfusion, or with the use of very large volumes of previously frozen or washed red cells. About 25 g of albumin per liter of erythrocytes is commonly used, although the requirements in preexistent hypoproteinemia or hepatic impairment can be greater. Albumin 20 is added to the isotonic suspension of washed red cells immediately prior to transfusion.
Acute Nephrosis
- Certain patients may not respond to cyclophosphamide or steroid therapy. The steroids may even aggravate the underlying edema. In this situation a loop diuretic and 100 mL albumin 20 repeated daily for 7 to 10 days may be helpful in controlling the edema and the patient may then respond to steroid treatment.
Renal Dialysis
- Although not part of the regular regimen of renal dialysis, albumin 20 may be of value in the treatment of shock or hypotension in these patients. The usual volume administered is about 100 mL, taking particular care to avoid fluid overload as these patients are often fluid overloaded and cannot tolerate substantial volumes of salt solution.
Situations in Which Albumin Administration is Not Warranted
- In chronic nephrosis, infused albumin is promptly excreted by the kidneys with no relief of the chronic edema or effect on the underlying renal lesion. It is of occasional use in the rapid “priming” diuresis of nephrosis. Similarly, in hypoproteinemic states associated with chronic cirrhosis, malabsorption, protein-losing enteropathies, pancreatic insufficiency, and undernutrition, the infusion of albumin as a source of protein nutrition is not justified.
# Dosage
Hypovolemic Shock — For treatment of hypovolemic shock, the volume administered and the speed of infusion should be adapted to the response of the individual patient.
Burns — After a burn injury (usually beyond 24 hours) there is a close correlation between the amount of albumin infused and the resultant increase in plasma colloid osmotic pressure. The aim should be to maintain the plasma albumin concentration in the region of 2.5 ± 0.5 g per 100 mL with a plasma oncotic pressure of 20 mm Hg (equivalent to a total plasma protein concentration of 5.2 g per 100 mL).(2) This is best achieved by the intravenous administration of albumin 20. The duration of therapy is decided by the loss of protein from the burned areas and in the urine. In addition, oral or parenteral feeding with amino acids should be initiated, as the long-term administration of albumin should not be considered as a source of nutrition.
Hypoproteinemia With or Without Edema — Unless the underlying pathology responsible for the hypoproteinemia can be corrected, the intravenous administration of albumin 20 must be considered purely symptomatic or supportive.The usual daily dose of albumin for adults is 50 to 75 g and for children 25 g. Patients with severe hypoproteinemia who continue to lose albumin may require larger quantities. Since hypoproteinemic patients usually have approximately normal blood volumes, the rate of administration of albumin 20 should not exceed 2 mL per minute, as more rapid injection may precipitate circulatory embarrassment and pulmonary edema.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Albumin in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Albumin in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Albumin in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Albumin in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Albumin in pediatric patients.
# Contraindications
- Certain patients, e.g., those with a history of congestive cardiac failure, renal insufficiency or stabilized chronic anemia, are at special risk of developing circulatory overload. A history of an allergic reaction to albumin is a specific contraindication to usage.
# Warnings
- Albumin (Human) 20%, USP (albumin™ 20) is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, and, theoretically, the Creutzfeldt-Jakob Disease (CJD) agent that can cause disease. The theoretical risk for transmission of CJD is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly hepatitis C. ALL infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Grifols Therapeutics Inc. [1-800-520-2807].
- The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering it to the patient.
- As with any hyperoncotic protein solution likely to be administered in large volumes, severe hemolysis and acute renal failure may result from the inappropriate use of Sterile Water for Injection as a diluent for Albumin (Human), 20%. Acceptable diluents include 0.9% Sodium Chloride or 5% Dextrose in Water.
- Solutions which have been frozen should not be used. Do not use if turbid. Do not begin administration more than 4 hours after the container has been entered. Partially used vials must be discarded. Vials which are cracked or which have been previously entered or damaged should not be used, as this may have allowed the entry of microorganisms. Glbumin 20 contains no preservative.
# Adverse Reactions
## Clinical Trials Experience
- Adverse reactions to albumin are rare. Such reactions may be allergic in nature or due to high plasma protein levels from excessive albumin administration. Allergic manifestations include urticaria, chills, fever, and changes in respiration, pulse and blood pressure.
## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Albumin in the drug label.
# Drug Interactions
- Albumin 20 is compatible with whole blood, packed red cells, as well as the standard carbohydrate and electrolyte solutions intended for intravenous use. It should, however, not be mixed with protein hydrolysates, amino acid solutions nor those containing alcohol.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
Pregnancy Category C
- Animal reproduction studies have not been conducted with albumin 20. It is also not known whether albumin 20 can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Albumin 20 should be given to a pregnant woman only if clearly needed.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Albumin in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Albumin during labor and delivery.
### Nursing Mothers
There is no FDA guidance on the use of Albumin with respect to nursing mothers.
### Pediatric Use
- Safety and effectiveness in the pediatric population have not been established.
### Geriatic Use
There is no FDA guidance on the use of Albumin with respect to geriatric patients.
### Gender
There is no FDA guidance on the use of Albumin with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Albumin with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Albumin in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Albumin in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Albumin in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Albumin in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Intravenous
- Albumin 20 should always be administered by intravenous infusion. Albuked 20 may be administered either undiluted or diluted in 0.9% Sodium Chloride or 5% Dextrose in Water. If sodium restriction is required, Albuked 20 should only be administered either undiluted or diluted in a sodium-free carbohydrate solution such as 5% Dextrose in Water.
- A number of factors beyond our control could reduce the efficacy of this product or even result in an ill effect following its use. These include improper storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration, and biological differences in individual patients. Because of these factors, it is important that this product be stored properly and that the directions be followed carefully during use.
Preparation for Administration
- Remove seal to expose stopper. Always swab stopper top immediately with a suitable antiseptic prior to entering vial.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
- Only 16 gauge needles or dispensing pins should be used with 20 mL vial sizes and larger. Needles or dispensing pins should only be inserted within the stopper area delineated by the raised ring. The stopper should be penetrated perpendicular to the plane of the stopper within the ring.
### Monitoring
There is limited information regarding Monitoring of Albumin in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Albumin in the drug label.
# Overdosage
There is limited information regarding Chronic Overdose of Albumin in the drug label.
# Pharmacology
## Mechanism of Action
There is limited information regarding Albumin Mechanism of Action in the drug label.
## Structure
There is limited information regarding Albumin Structure in the drug label.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Albumin in the drug label.
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Albumin in the drug label.
## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Albumin in the drug label.
# Clinical Studies
There is limited information regarding Clinical Studies of Albumin in the drug label.
# How Supplied
- Albuked 20 is available in 50 mL and 100 mL rubber-stoppered vials. Each single dose vial contains albumin in the following approximate amounts:
## Storage
- Store at room temperature not exceeding 30°C (86°F). Do not freeze. Do not use after expiration date.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Albumin in the drug label.
# Precautions with Alcohol
- Alcohol-Albumin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- ALBUKED®[1]
# Look-Alike Drug Names
- A® — B®[2]
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Albumin | |
b7c1f62f5d6a6fd65b7b92a3d244335dfc8e704d | wikidoc | Alcohol | Alcohol
# Overview
In layman's terms, the word alcohol (Arabic:الكحل al-kuḥl) usually refers to ethanol, also known as grain alcohol or (older) spirits of wine, or to any alcoholic beverage. Ethanol is a colorless, volatile liquid with a mild odor which can be obtained by the fermentation of sugars. (Industrially, it is more commonly obtained by ethylene hydration — the reaction of ethylene with water in the presence of phosphoric acid.) Ethanol is the most widely used depressant in the world, and has been for thousands of years. This sense underlies the term alcoholism (addiction to alcohol).
In chemistry, an alcohol is any organic compound in which a hydroxyl group (-OH) is bound to a carbon atom of an alkyl or substituted alkyl group. The general formula for a simple acyclic alcohol is CnH2n+1OH.
Other alcohols are usually described with a clarifying adjective, as in isopropyl alcohol (propan-2-ol) or wood alcohol (methyl alcohol, or methanol). The suffix -ol appears in the "official" IUPAC chemical name of all alcohols.
There are three major, subsets of alcohols: 'primary' (1°), 'secondary' (2°) and 'tertiary' (3°), based upon the number of carbons the C-OH carbon (shown in red) is bonded to. Ethanol is a simple 'primary' alcohol. The simplest secondary alcohol is isopropyl alcohol (propan-2-ol), and a simple tertiary alcohol is tert-butyl alcohol (2-methylpropan-2-ol).
The phenols with parent compound phenol have a hydroxyl group (attached to a benzene ring) just like alcohols, but differ sufficiently in properties as to warrant a separate treatment.
Carbohydrates (sugars) and sugar alcohols are an important class of compounds containing multiple alcohol functional groups. For example, sucrose (common sugar) contains eight hydroxyl groups per molecule and sorbitol has six. Most of the attributes of these polyols, from nomenclature, to occurrence, use and toxicity, are sufficiently different from simple aliphatic alcohols as to require a separate treatment.
# Simple alcohols
The simplest and most commonly used alcohols are methanol and ethanol. Methanol was formerly obtained by the distillation of wood and called "wood alcohol." It is now a cheap commodity, the chemical product of carbon monoxide reacting with hydrogen under high pressure. Methanol is intoxicating but not directly poisonous. It is toxic by its breakdown (toxication) by the enzyme alcohol dehydrogenase in the liver by forming formic acid and formaldehyde which cause permanent blindness by destruction of the optic nerve.
Apart from its familiar role in alcoholic beverages, ethanol is also used as a highly controlled industrial solvent and raw material. To avoid the high taxes on ethanol for consumption, additives are added to make it unpalatable (such as denatonium benzoate — "Bitrex") or poisonous (such as methanol). Ethanol in this form is known generally as denatured alcohol; when methanol is used, it may be referred to as methylated spirits ("Meths") or "surgical spirits".
Two other alcohols whose uses are relatively widespread (though not so much as those of methanol and ethanol) are propanol and butanol. Like ethanol, they can be produced by fermentation processes. (However, the fermenting agent is a bacterium, Clostridium acetobutylicum, that feeds on cellulose, not sugars like the Saccharomyces yeast that produces ethanol.)
# Nomenclature
## Systematic names
In the IUPAC system, the name of the alkane chain loses the terminal "e" and adds "ol", e.g. "methanol" and "ethanol". When necessary, the position of the hydroxyl group is indicated by a number between the alkane name and the "ol": propan-1-ol for CH3CH2CH2OH, propan-2-ol for CH3CH(OH)CH3. Sometimes, the position number is written before the IUPAC name: 1-propanol and 2-propanol. If a higher priority group is present (such as an aldehyde, ketone or carboxylic acid), then it is necessary to use the prefix "hydroxy", for example: 1-hydroxy-2-propanone (CH3COCH2OH).
Some examples of simple alcohols and how to name them:
Common names for alcohols usually takes name of the corresponding alkyl group and add the word "alcohol", e.g. methyl alcohol, ethyl alcohol or tert-butyl alcohol. Propyl alcohol may be n-propyl alcohol or isopropyl alcohol depending on whether the hydroxyl group is bonded to the 1st or 2nd carbon on the propane chain. Isopropyl alcohol is also occasionally called sec-propyl alcohol.
As mentioned above alcohols are classified as primary (1°), secondary (2°) or tertiary (3°), and common names often indicate this in the alkyl group prefix. For example (CH3)3COH is a tertiary alcohol is commonly known as tert-butyl alcohol. This would be named 2-methylpropan-2-ol under IUPAC rules, indicating a propane chain with methyl and hydroxyl groups both attached to the middle (#2) carbon.
## Etymology
The word "alcohol" almost certainly comes from the Arabic language (the "al-" prefix being the Arabic definite article); however, the precise origin is unclear. The Persian physician and scientist Rhazes discovered this substance, but because he wanted his book to be published in most of the then-known world, he used the Arabic language instead of Persian (although he made copies in Persian). The word was introduced into Europe, together with the art of distillation and the substance itself, around the 12th century by various European authors who translated and popularized the discoveries of Islamic and Persian alchemists.
A popular theory, found in many dictionaries, is that it comes from الكحل al-kuḥl, originally the name of very finely powdered antimony sulfide Sb2S3 used as an antiseptic and eyeliner. The powder is prepared by sublimation of the natural mineral stibnite in a closed vessel. According to this theory, the meaning of alkuhul would have been first extended to distilled substances in general, and then narrowed to ethanol. This conjectured etymology has been circulating in England since 1672 at least (OED).
However, this derivation is suspicious since the current Arabic name for alcohol, الكحول Template:ISOtranslit, does not derive from Template:ISOtranslit. The Qur'an, in verse 37:47, uses the word الغول Template:ISOtranslit — properly meaning "spirit" or "demon" — with the sense "the thing that gives the wine its headiness". The word Template:ISOtranslit is also the origin of the English word "ghoul", and the name of the star Algol. This derivation would, of course, be consistent with the use of "spirit" or "spirit of wine" as synonymous of "alcohol" in most Western languages.
According to the second theory, the popular etymology and the spelling "alcohol" would not be due to generalization of the meaning of al-kuḥl, but rather to Western alchemists and authors confusing the two words al-kuḥl and al-ghawl, which have indeed been transliterated in many different and overlapping ways.
# Physical and chemical properties
The hydroxyl group generally makes the alcohol molecule polar. Those groups can form hydrogen bonds to one another and to other compounds. This hydrogen bonding means that alcohols can be used as protic solvents. Two opposing solubility trends in alcohols are: the tendency of the polar OH to promote solubility in water, and of the carbon chain to resist it. Thus, methanol, ethanol, and propanol are miscible in water because the hydroxyl group wins out over the short carbon chain. Butanol, with a four-carbon chain, is moderately soluble because of a balance between the two trends. Alcohols of five or more carbons (Pentanol and higher) are effectively insoluble in water because of the hydrocarbon chain's dominance. All simple alcohols are miscible in organic solvents.
Because of hydrogen bonding, alcohols tend to have higher boiling points than comparable hydrocarbons and ethers. The boiling point of the alcohol ethanol is 78.29 °C, compared to 69 °C for the hydrocarbon Hexane (a common constituent of gasoline), and 34.6 °C for Diethyl ether.
Alcohols, like water, can show either acidic or basic properties at the O-H group. With a pKa of around 16-19 they are generally slightly weaker acids than water, but they are still able to react with strong bases such as sodium hydride or reactive metals such as sodium. The salts that result are called alkoxides, with the general formula RO- M+.
Meanwhile the oxygen atom has lone pairs of nonbonded electrons that render it weakly basic in the presence of strong acids such as sulfuric acid. For example, with methanol:
Alcohols can also undergo oxidation to give aldehydes, ketones or carboxylic acids, or they can be dehydrated to alkenes. They can react to form ester compounds, and they can (if activated first) undergo nucleophilic substitution reactions. The lone pairs of electrons on the oxygen of the hydroxyl group also makes alcohols nucleophiles. For more details see the reactions of alcohols section below.
# Applications
## Automotive
A 50 % v/v solution of ethylene glycol in water is commonly used as an antifreeze.
Some alcohols, mainly ethanol and methanol, can be used as an automotive fuel.
Performance can be increased in forced induction internal combustion engines by injecting alcohol into the air intake after the turbocharger or supercharger has pressurized the air. This cools the pressurized air, providing a denser air charge, which allows for more fuel, and therefore more power.
## Scientific, medical, and industrial
Alcohols have applications in industry and science as reagents or solvents. Because of its low toxicity and ability to dissolve non-polar substances, ethanol can be used as a solvent in medical drugs, perfumes, and vegetable essences such as vanilla. In organic synthesis, alcohols serve as versatile intermediates.
Ethanol can be used as an antiseptic to disinfect the skin before injections are given, often along with iodine. Ethanol-based soaps are becoming common in restaurants and are convenient because they do not require drying due to the volatility of the compound. Alcohol is also used as a preservative for specimens.
# Production
Industrially alcohols are produced in several ways:
- By fermentation using glucose produced from sugar from the hydrolysis of starch, in the presence of yeast and temperature of less than 37°C to produce ethanol. For instance the conversion of invertase to glucose and fructose or the conversion of glucose to zymase and ethanol.
- By direct hydration using ethylene (ethylene hydration or other alkenes from cracking of fractions of distilled crude oil. It usually uses a catalyst of phosphoric acid under high temperature and pressure of 50-120.
- Methanol is produced from synthesis gas, where carbon monoxide and 2 equivalents of hydrogen gas are combined to produce methanol using a copper, zinc oxide and aluminum oxide catalyst at 250°C and a pressure of 50-100 atm.
# Laboratory synthesis
Several methods exist for the preparation of alcohols in the laboratory.
- Primary alkyl halides react with aqueous NaOH or KOH mainly to primary alcohols in [[nucleophilic aliphatic substitution. (Secondary and especially tertiary alkyl halides will give the elimination (alkene) product instead).
- Aldehydes or ketones are reduced with sodium borohydride or lithium aluminium hydride (after an acidic workup). Another reduction by aluminumisopropylates is the Meerwein-Ponndorf-Verley reduction.
- Alkenes engage in an acid catalysed hydration reaction using concentrated sulfuric acid as a catalyst which gives usually secondary or tertiary alcohols.
- The hydroboration-oxidation and oxymercuration-reduction of alkenes are more reliable in organic synthesis.
- Grignard reagents react with carbonyl groups to secondary and tertiary alcohols
- Noyori asymmetric hydrogenation is the asymmetric reduction of β-keto-esters
The formation of a secondary alcohol via reduction and hydration is shown:
# Reactions
## Deprotonation
Alcohols can behave as weak acids, undergoing deprotonation. The deprotonation reaction to produce an alkoxide salt is either performed with a strong base such as sodium hydride or n-butyllithium, or with sodium or potassium metal.
Water is similar in pKa to many alcohols, so with sodium hydroxide there is an equilibrium set up which usually lies to the left:
It should be noted, though, that the bases used to deprotonate alcohols are strong themselves. The bases used and the alkoxides created are both highly moisture sensitive chemical reagents.
The acidity of alcohols is also affected by the overall stability of the alkoxide ion. Electron-withdrawing groups attached to the carbon containing the hydroxyl group will serve to stabilize the alkoxide when formed, thus resulting in greater acidity. On the other hand, the presence of electron-donating group will result in a less stable alkoxide ion formed. This will result in a scenario whereby the unstable alkoxide ion formed will tend to accept a proton to reform the original alcohol.
With alkyl halides alkoxides give rise to ethers in the Williamson ether synthesis.
## Nucleophilic substitution
The OH group is not a good leaving group in nucleophilic substitution reactions, so neutral alcohols do not react in such reactions. However if the oxygen is first protonated to give R−OH2+, the leaving group (water) is much more stable, and nucleophilic substitution can take place. For instance, tertiary alcohols react with hydrochloric acid to produce tertiary alkyl halides, where the hydroxyl group is replaced by a chlorine atom. If primary or secondary alcohols are to be reacted with hydrochloric acid, an activator such as zinc chloride is needed. Alternatively the conversion may be performed directly using thionyl chloride.
Alcohols may likewise be converted to alkyl bromides using hydrobromic acid or phosphorus tribromide, for example:
In the Barton-McCombie deoxygenation an alcohol is deoxygenated to an alkane with tributyltin hydride or a trimethylborane-water complex in a radical substitution reaction.
## Dehydration
Alcohols are themselves nucleophilic, so R−OH2+ can react with ROH to produce ethers and water in a dehydration reaction, although this reaction is rarely used except in the manufacture of diethyl ether.
More useful is the E1 elimination reaction of alcohols to produce alkenes. The reaction generally obeys Zaitsev's Rule, which states that the most stable (usually the most substituted) alkene is formed. Tertiary alcohols eliminate easily at just above room temperature, but primary alcohols require a higher temperature.
This is a diagram of acid catalysed dehydration of ethanol to produce ethene:
A more controlled elimination reaction is the Chugaev elimination with carbon disulfide and iodomethane.
## Esterification
To form an ester from an alcohol and a carboxylic acid the reaction, known as Fischer esterification, is usually performed at reflux with a catalyst of concentrated sulfuric acid:
In order to drive the equilibrium to the right and produce a good yield of ester, water is usually removed, either by an excess of H2SO4 or by using a Dean-Stark apparatus. Esters may also be prepared by reaction of the alcohol with an acid chloride in the presence of a base such as pyridine.
Other types of ester are prepared similarly- for example tosyl (tosylate) esters are made by reaction of the alcohol with p-toluenesulfonyl chloride in pyridine.
## Oxidation
Primary alcohols (R-CH2-OH) can be oxidized either to aldehydes (R-CHO) or to carboxylic acids (R-CO2H), while the oxidation of secondary alcohols (R1R²CH-OH) normally terminates at the ketone (R1R²C=O) stage. Tertiary alcohols (R1R²R³C-OH) are resistant to oxidation.
The direct oxidation of primary alcohols to carboxylic acids normally proceeds via the corresponding aldehyde, which is transformed via an aldehyde hydrate (R-CH(OH)2) by reaction with water before it can be further oxidized to the carboxylic acid.
Often it is possible to interrupt the oxidation of a primary alcohol at the aldehyde level by performing the reaction in absence of water, so that no aldehyde hydrate can be formed.
Reagents useful for the transformation of primary alcohols to aldehydes are normally also suitable for the oxidation of secondary alcohols to ketones. These include:
- Chromium-based reagents, such as Collins reagent (CrO3·Py2), PDC or PCC.
- Activated DMSO, resulting from reaction of DMSO with electrophiles, such as oxalyl chloride (Swern oxidation), a carbodiimide (Pfitzner-Moffatt oxidation) or the complex SO3·Py (Parikh-Doering oxidation).
- Hypervalent iodine compounds, such as Dess-Martin periodinane or 2-Iodoxybenzoic acid.
- Catalytic TPAP in presence of excess of NMO (Ley oxidation).
- Catalytic TEMPO in presence of excess bleach (NaOCl) (Anelli’s oxidation).
Allylic and benzylic alcohols can be oxidized in presence of other alcohols using certain selective oxidants such as manganese dioxide (MnO2).
Reagents useful for the oxidation of secondary alcohols to ketones, but normally inefficient for oxidation of primary alcohols to aldehydes, include chromium trioxide (CrO3) in a mixture of sulfuric acid and acetone (Jones oxidation) and certain ketones, such as cyclohexanone, in the presence of aluminium isopropoxide (Oppenauer oxidation).
The direct oxidation of primary alcohols to carboxylic acids can be carried out using:
- Potassium permanganate (KMnO4).
- Jones oxidation.
- PDC in DMF.
- Heyns oxidation.
- Ruthenium tetroxide (RuO4).
- TEMPO.
Alcohols possessing two hydroxy groups located on adjacent carbons —that is, 1,2-diols— suffer oxidative breakage at a carbon-carbon bond with some oxidants such as sodium periodate (NaIO4) or lead tetraacetate (Pb(OAc)4), resulting in generation of two carbonyl groups.
# Toxicity
Alcohols often have an odor described as 'biting' that 'hangs' in the nasal passages. Ethanol in the form of alcoholic beverages has been consumed by humans since pre-historic times, for a variety of hygienic, dietary, medicinal, religious, and recreational reasons. The consumption of large doses result in drunkenness or intoxication (which may lead to a hangover as the effect wears off) and, depending on the dose and regularity of use, can cause acute respiratory failure or death and with chronic use has medical repercussions. Because alcohol impairs judgment, it can often be a catalyst for reckless or irresponsible behavior. The LD50 of ethanol in rats is 11,300 mg/kg. This ratio would correspond to an 80kg (176.4lb) man drinking 65 shots of 80 proof alcohol, although the LD50 does not necessarily translate directly to humans.
Other alcohols are substantially more poisonous than ethanol, partly because they take much longer to be metabolized, and often their metabolism produces even more toxic substances. Methanol, or wood alcohol, for instance, is oxidized by alcohol dehydrogenase enzymes in the liver to the poisonous formaldehyde, which can cause blindness or death.
An effective treatment to prevent formaldehyde toxicity after methanol ingestion is to administer ethanol. Alcohol dehydrogenase has a higher affinity for ethanol, thus preventing methanol from binding and acting as a substrate. Any remaining methanol will then have time to be excreted through the kidneys. Remaining formaldehyde will be converted to formic acid and excreted. | Alcohol
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
In layman's terms, the word alcohol (Arabic:الكحل al-kuḥl) usually refers to ethanol, also known as grain alcohol or (older) spirits of wine, or to any alcoholic beverage. Ethanol is a colorless, volatile liquid with a mild odor which can be obtained by the fermentation of sugars. (Industrially, it is more commonly obtained by ethylene hydration — the reaction of ethylene with water in the presence of phosphoric acid.[1]) Ethanol is the most widely used depressant in the world, and has been for thousands of years. This sense underlies the term alcoholism (addiction to alcohol).
In chemistry, an alcohol is any organic compound in which a hydroxyl group (-OH) is bound to a carbon atom of an alkyl or substituted alkyl group. The general formula for a simple acyclic alcohol is CnH2n+1OH.
Other alcohols are usually described with a clarifying adjective, as in isopropyl alcohol (propan-2-ol) or wood alcohol (methyl alcohol, or methanol). The suffix -ol appears in the "official" IUPAC chemical name of all alcohols.
There are three major, subsets of alcohols: 'primary' (1°), 'secondary' (2°) and 'tertiary' (3°), based upon the number of carbons the C-OH carbon (shown in red) is bonded to. Ethanol is a simple 'primary' alcohol. The simplest secondary alcohol is isopropyl alcohol (propan-2-ol), and a simple tertiary alcohol is tert-butyl alcohol (2-methylpropan-2-ol).
The phenols with parent compound phenol have a hydroxyl group (attached to a benzene ring) just like alcohols, but differ sufficiently in properties as to warrant a separate treatment.
Carbohydrates (sugars) and sugar alcohols are an important class of compounds containing multiple alcohol functional groups. For example, sucrose (common sugar) contains eight hydroxyl groups per molecule and sorbitol has six. Most of the attributes of these polyols, from nomenclature, to occurrence, use and toxicity, are sufficiently different from simple aliphatic alcohols as to require a separate treatment.
# Simple alcohols
The simplest and most commonly used alcohols are methanol and ethanol. Methanol was formerly obtained by the distillation of wood and called "wood alcohol." It is now a cheap commodity, the chemical product of carbon monoxide reacting with hydrogen under high pressure.[citation needed] Methanol is intoxicating but not directly poisonous. It is toxic by its breakdown (toxication) by the enzyme alcohol dehydrogenase in the liver by forming formic acid and formaldehyde which cause permanent blindness by destruction of the optic nerve.[2]
Apart from its familiar role in alcoholic beverages, ethanol is also used as a highly controlled industrial solvent and raw material. To avoid the high taxes on ethanol for consumption, additives are added to make it unpalatable (such as denatonium benzoate — "Bitrex") or poisonous (such as methanol). Ethanol in this form is known generally as denatured alcohol; when methanol is used, it may be referred to as methylated spirits ("Meths") or "surgical spirits".
Two other alcohols whose uses are relatively widespread (though not so much as those of methanol and ethanol) are propanol and butanol. Like ethanol, they can be produced by fermentation processes. (However, the fermenting agent is a bacterium, Clostridium acetobutylicum, that feeds on cellulose, not sugars like the Saccharomyces yeast that produces ethanol.)
# Nomenclature
## Systematic names
In the IUPAC system, the name of the alkane chain loses the terminal "e" and adds "ol", e.g. "methanol" and "ethanol".[3] When necessary, the position of the hydroxyl group is indicated by a number between the alkane name and the "ol": propan-1-ol for CH3CH2CH2OH, propan-2-ol for CH3CH(OH)CH3. Sometimes, the position number is written before the IUPAC name: 1-propanol and 2-propanol. If a higher priority group is present (such as an aldehyde, ketone or carboxylic acid), then it is necessary to use the prefix "hydroxy",[3] for example: 1-hydroxy-2-propanone (CH3COCH2OH).
Some examples of simple alcohols and how to name them:
Common names for alcohols usually takes name of the corresponding alkyl group and add the word "alcohol", e.g. methyl alcohol, ethyl alcohol or tert-butyl alcohol. Propyl alcohol may be n-propyl alcohol or isopropyl alcohol depending on whether the hydroxyl group is bonded to the 1st or 2nd carbon on the propane chain. Isopropyl alcohol is also occasionally called sec-propyl alcohol.
As mentioned above alcohols are classified as primary (1°), secondary (2°) or tertiary (3°), and common names often indicate this in the alkyl group prefix. For example (CH3)3COH is a tertiary alcohol is commonly known as tert-butyl alcohol. This would be named 2-methylpropan-2-ol under IUPAC rules, indicating a propane chain with methyl and hydroxyl groups both attached to the middle (#2) carbon.
## Etymology
The word "alcohol" almost certainly comes from the Arabic language (the "al-" prefix being the Arabic definite article); however, the precise origin is unclear. The Persian physician and scientist Rhazes discovered this substance, but because he wanted his book to be published in most of the then-known world, he used the Arabic language instead of Persian (although he made copies in Persian). The word was introduced into Europe, together with the art of distillation and the substance itself, around the 12th century by various European authors who translated and popularized the discoveries of Islamic and Persian alchemists.[4]
A popular theory, found in many dictionaries, is that it comes from الكحل al-kuḥl, originally the name of very finely powdered antimony sulfide Sb2S3 used as an antiseptic and eyeliner. The powder is prepared by sublimation of the natural mineral stibnite in a closed vessel. According to this theory, the meaning of alkuhul would have been first extended to distilled substances in general, and then narrowed to ethanol. This conjectured etymology has been circulating in England since 1672 at least (OED).
However, this derivation is suspicious since the current Arabic name for alcohol, الكحول Template:ISOtranslit, does not derive from Template:ISOtranslit.[citation needed] The Qur'an, in verse 37:47, uses the word الغول Template:ISOtranslit — properly meaning "spirit" or "demon" — with the sense "the thing that gives the wine its headiness". The word Template:ISOtranslit is also the origin of the English word "ghoul", and the name of the star Algol. This derivation would, of course, be consistent with the use of "spirit" or "spirit of wine" as synonymous of "alcohol" in most Western languages.
According to the second theory, the popular etymology and the spelling "alcohol" would not be due to generalization of the meaning of al-kuḥl, but rather to Western alchemists and authors confusing the two words al-kuḥl and al-ghawl, which have indeed been transliterated in many different and overlapping ways.
# Physical and chemical properties
The hydroxyl group generally makes the alcohol molecule polar. Those groups can form hydrogen bonds to one another and to other compounds. This hydrogen bonding means that alcohols can be used as protic solvents. Two opposing solubility trends in alcohols are: the tendency of the polar OH to promote solubility in water, and of the carbon chain to resist it. Thus, methanol, ethanol, and propanol are miscible in water because the hydroxyl group wins out over the short carbon chain. Butanol, with a four-carbon chain, is moderately soluble because of a balance between the two trends. Alcohols of five or more carbons (Pentanol and higher) are effectively insoluble in water because of the hydrocarbon chain's dominance. All simple alcohols are miscible in organic solvents.
Because of hydrogen bonding, alcohols tend to have higher boiling points than comparable hydrocarbons and ethers. The boiling point of the alcohol ethanol is 78.29 °C, compared to 69 °C for the hydrocarbon Hexane (a common constituent of gasoline), and 34.6 °C for Diethyl ether.
Alcohols, like water, can show either acidic or basic properties at the O-H group. With a pKa of around 16-19 they are generally slightly weaker acids than water, but they are still able to react with strong bases such as sodium hydride or reactive metals such as sodium. The salts that result are called alkoxides, with the general formula RO- M+.
Meanwhile the oxygen atom has lone pairs of nonbonded electrons that render it weakly basic in the presence of strong acids such as sulfuric acid. For example, with methanol:
Alcohols can also undergo oxidation to give aldehydes, ketones or carboxylic acids, or they can be dehydrated to alkenes. They can react to form ester compounds, and they can (if activated first) undergo nucleophilic substitution reactions. The lone pairs of electrons on the oxygen of the hydroxyl group also makes alcohols nucleophiles. For more details see the reactions of alcohols section below.
# Applications
## Automotive
A 50 % v/v solution of ethylene glycol in water is commonly used as an antifreeze.
Some alcohols, mainly ethanol and methanol, can be used as an automotive fuel.
Performance can be increased in forced induction internal combustion engines by injecting alcohol into the air intake after the turbocharger or supercharger has pressurized the air. This cools the pressurized air, providing a denser air charge, which allows for more fuel, and therefore more power.
## Scientific, medical, and industrial
Alcohols have applications in industry and science as reagents or solvents. Because of its low toxicity and ability to dissolve non-polar substances, ethanol can be used as a solvent in medical drugs, perfumes, and vegetable essences such as vanilla. In organic synthesis, alcohols serve as versatile intermediates.
Ethanol can be used as an antiseptic to disinfect the skin before injections are given, often along with iodine. Ethanol-based soaps are becoming common in restaurants and are convenient because they do not require drying due to the volatility of the compound. Alcohol is also used as a preservative for specimens.
# Production
Industrially alcohols are produced in several ways:
- By fermentation using glucose produced from sugar from the hydrolysis of starch, in the presence of yeast and temperature of less than 37°C to produce ethanol. For instance the conversion of invertase to glucose and fructose or the conversion of glucose to zymase and ethanol.
- By direct hydration using ethylene (ethylene hydration[1] or other alkenes from cracking of fractions of distilled crude oil. It usually uses a catalyst of phosphoric acid under high temperature and pressure of 50-120.[citation needed]
- Methanol is produced from synthesis gas, where carbon monoxide and 2 equivalents of hydrogen gas are combined to produce methanol using a copper, zinc oxide and aluminum oxide catalyst at 250°C and a pressure of 50-100 atm.[citation needed]
# Laboratory synthesis
Several methods exist for the preparation of alcohols in the laboratory.
- Primary alkyl halides react with aqueous NaOH or KOH mainly to primary alcohols in [[nucleophilic aliphatic substitution. (Secondary and especially tertiary alkyl halides will give the elimination (alkene) product instead).
- Aldehydes or ketones are reduced with sodium borohydride or lithium aluminium hydride (after an acidic workup). Another reduction by aluminumisopropylates is the Meerwein-Ponndorf-Verley reduction.
- Alkenes engage in an acid catalysed hydration reaction using concentrated sulfuric acid as a catalyst which gives usually secondary or tertiary alcohols.
- The hydroboration-oxidation and oxymercuration-reduction of alkenes are more reliable in organic synthesis.
- Grignard reagents react with carbonyl groups to secondary and tertiary alcohols
- Noyori asymmetric hydrogenation is the asymmetric reduction of β-keto-esters
The formation of a secondary alcohol via reduction and hydration is shown:
# Reactions
## Deprotonation
Alcohols can behave as weak acids, undergoing deprotonation. The deprotonation reaction to produce an alkoxide salt is either performed with a strong base such as sodium hydride or n-butyllithium, or with sodium or potassium metal.
Water is similar in pKa to many alcohols, so with sodium hydroxide there is an equilibrium set up which usually lies to the left:
It should be noted, though, that the bases used to deprotonate alcohols are strong themselves. The bases used and the alkoxides created are both highly moisture sensitive chemical reagents.
The acidity of alcohols is also affected by the overall stability of the alkoxide ion. Electron-withdrawing groups attached to the carbon containing the hydroxyl group will serve to stabilize the alkoxide when formed, thus resulting in greater acidity. On the other hand, the presence of electron-donating group will result in a less stable alkoxide ion formed. This will result in a scenario whereby the unstable alkoxide ion formed will tend to accept a proton to reform the original alcohol.
With alkyl halides alkoxides give rise to ethers in the Williamson ether synthesis.
## Nucleophilic substitution
The OH group is not a good leaving group in nucleophilic substitution reactions, so neutral alcohols do not react in such reactions. However if the oxygen is first protonated to give R−OH2+, the leaving group (water) is much more stable, and nucleophilic substitution can take place. For instance, tertiary alcohols react with hydrochloric acid to produce tertiary alkyl halides, where the hydroxyl group is replaced by a chlorine atom. If primary or secondary alcohols are to be reacted with hydrochloric acid, an activator such as zinc chloride is needed. Alternatively the conversion may be performed directly using thionyl chloride.[1]
Alcohols may likewise be converted to alkyl bromides using hydrobromic acid or phosphorus tribromide, for example:
In the Barton-McCombie deoxygenation an alcohol is deoxygenated to an alkane with tributyltin hydride or a trimethylborane-water complex in a radical substitution reaction.
## Dehydration
Alcohols are themselves nucleophilic, so R−OH2+ can react with ROH to produce ethers and water in a dehydration reaction, although this reaction is rarely used except in the manufacture of diethyl ether.
More useful is the E1 elimination reaction of alcohols to produce alkenes. The reaction generally obeys Zaitsev's Rule, which states that the most stable (usually the most substituted) alkene is formed. Tertiary alcohols eliminate easily at just above room temperature, but primary alcohols require a higher temperature.
This is a diagram of acid catalysed dehydration of ethanol to produce ethene:
A more controlled elimination reaction is the Chugaev elimination with carbon disulfide and iodomethane.
## Esterification
To form an ester from an alcohol and a carboxylic acid the reaction, known as Fischer esterification, is usually performed at reflux with a catalyst of concentrated sulfuric acid:
In order to drive the equilibrium to the right and produce a good yield of ester, water is usually removed, either by an excess of H2SO4 or by using a Dean-Stark apparatus. Esters may also be prepared by reaction of the alcohol with an acid chloride in the presence of a base such as pyridine.
Other types of ester are prepared similarly- for example tosyl (tosylate) esters are made by reaction of the alcohol with p-toluenesulfonyl chloride in pyridine.
## Oxidation
Primary alcohols (R-CH2-OH) can be oxidized either to aldehydes (R-CHO) or to carboxylic acids (R-CO2H), while the oxidation of secondary alcohols (R1R²CH-OH) normally terminates at the ketone (R1R²C=O) stage. Tertiary alcohols (R1R²R³C-OH) are resistant to oxidation.
The direct oxidation of primary alcohols to carboxylic acids normally proceeds via the corresponding aldehyde, which is transformed via an aldehyde hydrate (R-CH(OH)2) by reaction with water before it can be further oxidized to the carboxylic acid.
Often it is possible to interrupt the oxidation of a primary alcohol at the aldehyde level by performing the reaction in absence of water, so that no aldehyde hydrate can be formed.
Reagents useful for the transformation of primary alcohols to aldehydes are normally also suitable for the oxidation of secondary alcohols to ketones. These include:
- Chromium-based reagents, such as Collins reagent (CrO3·Py2), PDC or PCC.
- Activated DMSO, resulting from reaction of DMSO with electrophiles, such as oxalyl chloride (Swern oxidation), a carbodiimide (Pfitzner-Moffatt oxidation) or the complex SO3·Py (Parikh-Doering oxidation).
- Hypervalent iodine compounds, such as Dess-Martin periodinane or 2-Iodoxybenzoic acid.
- Catalytic TPAP in presence of excess of NMO (Ley oxidation).
- Catalytic TEMPO in presence of excess bleach (NaOCl) (Anelli’s oxidation).
Allylic and benzylic alcohols can be oxidized in presence of other alcohols using certain selective oxidants such as manganese dioxide (MnO2).
Reagents useful for the oxidation of secondary alcohols to ketones, but normally inefficient for oxidation of primary alcohols to aldehydes, include chromium trioxide (CrO3) in a mixture of sulfuric acid and acetone (Jones oxidation) and certain ketones, such as cyclohexanone, in the presence of aluminium isopropoxide (Oppenauer oxidation).
The direct oxidation of primary alcohols to carboxylic acids can be carried out using:
- Potassium permanganate (KMnO4).
- Jones oxidation.
- PDC in DMF.
- Heyns oxidation.
- Ruthenium tetroxide (RuO4).
- TEMPO.
Alcohols possessing two hydroxy groups located on adjacent carbons —that is, 1,2-diols— suffer oxidative breakage at a carbon-carbon bond with some oxidants such as sodium periodate (NaIO4) or lead tetraacetate (Pb(OAc)4), resulting in generation of two carbonyl groups.
# Toxicity
Alcohols often have an odor described as 'biting' that 'hangs' in the nasal passages. Ethanol in the form of alcoholic beverages has been consumed by humans since pre-historic times, for a variety of hygienic, dietary, medicinal, religious, and recreational reasons. The consumption of large doses result in drunkenness or intoxication (which may lead to a hangover as the effect wears off) and, depending on the dose and regularity of use, can cause acute respiratory failure or death and with chronic use has medical repercussions. Because alcohol impairs judgment, it can often be a catalyst for reckless or irresponsible behavior. The LD50 of ethanol in rats is 11,300 mg/kg.[5] This ratio would correspond to an 80kg (176.4lb) man drinking 65 shots of 80 proof alcohol, although the LD50 does not necessarily translate directly to humans.
Other alcohols are substantially more poisonous than ethanol, partly because they take much longer to be metabolized, and often their metabolism produces even more toxic substances. Methanol, or wood alcohol, for instance, is oxidized by alcohol dehydrogenase enzymes in the liver to the poisonous formaldehyde, which can cause blindness or death.[2]
An effective treatment to prevent formaldehyde toxicity after methanol ingestion is to administer ethanol. Alcohol dehydrogenase has a higher affinity for ethanol, thus preventing methanol from binding and acting as a substrate. Any remaining methanol will then have time to be excreted through the kidneys. Remaining formaldehyde will be converted to formic acid and excreted. | https://www.wikidoc.org/index.php/Alcohol | |
7dbadeb7726d81f89de33356e38b94cad0ff9e55 | wikidoc | Ethanol | Ethanol
# Overview
Ethanol, also known as ethyl alcohol, drinking alcohol or grain alcohol, is a flammable, colorless, slightly toxic chemical compound, and is best known as the alcohol found in alcoholic beverages. In common usage, it is often referred to simply as alcohol. Its molecular formula is variously represented as EtOH, CH3CH2OH, C2H5OH or as its empirical formula C2H6O (which it shares with dimethyl ether).
After the use of fire, fermentation of sugar into ethanol is perhaps the earliest organic reaction known to humanity, and the intoxicating effects of ethanol consumption have certainly been known since ancient times. In modern times ethanol intended for industrial use has also been produced from byproducts of petroleum refining.
Because of ethanol's ease of production and its low toxicity, it finds widespread use as a solvent for substances intended for human contact or consumption, including scents, flavorings, colorings, and medicines. In chemistry it is both an essential solvent and a fundamental feedstock for the synthesis of other products. Because it burns cleanly, ethanol has a long history as a fuel, including as a fuel for internal combustion engines.
# History
Ethanol has been used by humans since prehistory as the intoxicating ingredient in alcoholic beverages. Dried residues on 9000-year-old pottery found in northern mainland China imply the use of alcoholic beverages even among Neolithic peoples. Its isolation as a relatively pure compound was first achieved by Persian alchemists who developed the art of distillation during the Abbasid caliphate, the most notable of whom was Al-Razi. The writings attributed to Jabir Ibn Hayyan (Geber) (721-815) mention the flammable vapors of boiled wine. Al-Kindī (801-873) unambiguously described the distillation of wine. Absolute ethanol was first obtained in 1796 by Johann Tobias Lowitz, by filtering distilled ethanol through charcoal.
Antoine Lavoisier described ethanol as a compound of carbon, hydrogen, and oxygen, and in 1808, Nicolas-Théodore de Saussure determined ethanol's chemical formula. Fifty years later Archibald Scott Couper published a structural formula for ethanol, which places ethanol among the first of chemical compounds to have its chemical structures determined.
Ethanol was first prepared synthetically in 1826, through the independent efforts of Henry Hennel in Great Britain and S.G. Sérullas in France. Michael Faraday prepared ethanol by the acid-catalyzed hydration of ethylene in 1828, in a process similar to that used for industrial ethanol synthesis today.
Ethanol served as lamp fuel in the United States as early as 1840, although taxes levied during the Civil War on industrial alcohol rendered the practice uneconomical. The tax was not repealed until 1906, and by 1908 ethanol was used to power early Model T automobiles. With the advent of Prohibition in 1920 though, sellers of ethanol fuel were accused of being allies of moonshiners, and ethanol fuel once again faded from the public eye. The recent rise in oil prices has spurred renewed interest.
# Physical properties
The properties of ethanol stem primarily from the presence of its hydroxyl group and the shortness of its carbon chain. Ethanol's hydroxyl group is able to participate in hydrogen bonding, rendering it more viscous and less volatile than less polar organic compounds of similar molecular weight. Ethanol, like most short-chain alcohols, is flammable, colorless, has a strong odor, and is volatile.
Ethanol is slightly more refractive than water with a refractive index of 1.36242 (at λ=589.3 nm and 18.35 °C).
Ethanol is a versatile solvent, miscible in all proportions with water and many organic solvents, including acetic acid, acetone, benzene, carbon tetrachloride, chloroform, diethyl ether, ethylene glycol, glycerol, nitromethane, pyridine, and toluene. It is also miscible with light aliphatic hydrocarbons such as pentane and hexane, as well as aliphatic chlorides such as trichloroethane and tetrachloroethylene. Ethanol's miscibility with water is in contrast to longer chain alcohols (five or more carbons), whose water solubility decreases rapidly as the number of carbons increases.
Hydrogen bonding causes pure ethanol to be hygroscopic to the extent that it readily absorbs water from the air. The polar nature of the hydroxyl group causes ethanol to dissolve many ionic compounds, notably sodium and potassium hydroxides, magnesium chloride, calcium chloride, ammonium chloride, ammonium bromide, and sodium bromide. Sodium and potassium chlorides are slightly soluble in ethanol. Because the ethanol molecule also has a nonpolar end, it also dissolves nonpolar substances, including most essential oils, as well as numerous flavoring, coloring, and medicinal agents.
Several unusual phenomena are associated with mixtures of ethanol and water. Ethanol-water mixtures have less volume than their individual components. A mixture of equal volumes ethanol and water has only 95.6% of the volume of equal parts ethanol and water, unmixed (at 15.56 °C). The addition of even a few percent of ethanol to water sharply reduces the surface tension of water. This property partially explains the tears of wine phenomenon. When wine is swirled in a glass, ethanol evaporates quickly from the thin film of wine on the wall of the glass. As its ethanol content decreases, its surface tension increases, and the thin film beads up and runs down the glass in channels rather than as a smooth sheet.
Ethanol and mixtures with water greater than about 50% ethanol are flammable and easily ignited. Ethanol-water solutions below 50% ethanol by volume may also be flammable if the solution is vaporized by heating (as in some cooking methods that call for wine to be added to a hot pan, causing it to flash boil into a vapor, which is then ignited to "burn off" excessive alcohol).
# Chemistry
Ethanol is classified as a primary alcohol, meaning that the carbon to which its hydroxyl group is attached has at least two hydrogen atoms attached to it as well.
The chemistry of ethanol is largely that of its hydroxyl group.
Ethanol's hydroxyl proton is very weakly acidic; it is an even weaker acid than water. Ethanol can be quantitatively converted to its conjugate base, the ethoxide ion (CH3CH2O−), by reaction with an alkali metal such as sodium:
Under special conditions, ethanol reacts with hydrogen halides to produce ethyl halides such as ethyl chloride and ethyl bromide:
HCl reaction requires a catalyst such as zinc chloride.
HBr requires refluxing with a sulfuric acid catalyst.
Ethyl halides can also be produced by reacting ethanol with more specialized halogenating agents, such as thionyl chloride for preparing ethyl chloride, or phosphorus tribromide for preparing ethyl bromide.
Under acid-catalyzed conditions, ethanol reacts with carboxylic acids to produce ethyl esters and water:
For this reaction to produce useful yields it is necessary to remove water from the reaction mixture as it is formed.
Ethanol can also form esters with inorganic acids. Diethyl sulfate and triethyl phosphate, prepared by reacting ethanol with sulfuric and phosphoric acid respectively, are both useful ethylating agents in organic synthesis. Ethyl nitrite, prepared from the reaction of ethanol with sodium nitrite and sulfuric acid, was formerly a widely-used diuretic.
Strong acid desiccants, such as sulfuric acid, cause ethanol's dehydration to form either diethyl ether or ethylene:
Which product, diethyl ether or ethylene, predominates depends on the precise reaction conditions.
Ethanol can be oxidized to acetaldehyde, and further oxidized to acetic acid. In the human body, these oxidation reactions are catalyzed by enzymes. In the laboratory, aqueous solutions of strong oxidizing agents, such as chromic acid or potassium permanganate, oxidize ethanol to acetic acid, and it is difficult to stop the reaction at acetaldehyde at high yield. Ethanol can be oxidized to acetaldehyde, without over oxidation to acetic acid, by reacting it with pyridinium chromic chloride.
When exposed to chlorine, ethanol is both oxidized and its alpha carbon chlorinated to form the compound, chloral.
Combustion of ethanol forms carbon dioxide and water:
# Production
Ethanol is produced both as a petrochemical, through the hydration of ethylene, and biologically, by fermenting sugars with yeast. Which process is more economical is dependent upon the prevailing prices of petroleum and of grain feed stocks.
## Ethylene hydration
Ethanol for use as industrial feedstock is most often made from petrochemical feed stocks, typically by the acid-catalyzed hydration of ethylene, represented by the chemical equation
The catalyst is most commonly phosphoric acid, adsorbed onto a porous support such as diatomaceous earth or charcoal. This catalyst was first used for large-scale ethanol production by the Shell Oil Company in 1947. The reaction is carried out at with an excess of high pressure steam at 300 °C.
In an older process, first practiced on the industrial scale in 1930 by Union Carbide, but now almost entirely obsolete, ethylene was hydrated indirectly by reacting it with concentrated sulfuric acid to produce ethyl sulfate, which was then hydrolyzed to yield ethanol and regenerate the sulfuric acid:
## Fermentation
Ethanol for use in alcoholic beverages, and the vast majority of ethanol for use as fuel, is produced by fermentation. When certain species of yeast, most importantly, Saccharomyces cerevisiae, metabolize sugar in the absence of oxygen, they produce ethanol and carbon dioxide. The chemical equation below summarizes the conversion:
The process of culturing yeast under conditions to produce alcohol is called as brewing. Ethanol's toxicity to yeast limits the ethanol concentration obtainable by brewing. The most ethanol-tolerant strains of yeast can survive up to approximately 15% ethanol by volume.
The fermentation process must exclude oxygen. If oxygen is present, yeast undergo aerobic respiration which produces carbon dioxide and water rather than ethanol.
In order to produce ethanol from starchy materials such as cereal grains, the starch must first be converted into sugars. In brewing beer, this has traditionally been accomplished by allowing the grain to germinate, or malt, which produces the enzyme, amylase. When the malted grain is mashed, the amylase converts the remaining starches into sugars. For fuel ethanol, the hydrolysis of starch into glucose can be accomplished more rapidly by treatment with dilute sulfuric acid, fungally produced amylase, or some combination of the two.
## Cellulosic ethanol
Sugars for ethanol fermentation can be obtained from cellulose. Until recently, however, the cost of the cellulase enzymes capable of hydrolyzing cellulose has been prohibitive. The Canadian firm, Iogen, brought the first cellulose-based ethanol plant on-stream in 2004. Its primary consumer so far has been the Canadian government, which, along with the United States Department of Energy, has invested heavily in the commercialization of cellulosic ethanol. Deployment of this technology could turn a number of cellulose-containing agricultural byproducts, such as corncobs, straw, and sawdust, into renewable energy resources. Other enzyme companies are developing genetically engineered fungi that produce large volumes of cellulase, xylanase and hemicellulase enzymes. These would convert agricultural residues such as corn stover, wheat straw and sugar cane bagasse and energy crops such as switchgrass into fermentable sugars.
Cellulose-bearing materials typically also contain other polysaccharides, including hemicellulose. When hydrolyzed, hemicellulose decomposes into mostly five-carbon sugars such as xylose. S. cerevisiae, the yeast most commonly used for ethanol production, cannot metabolize xylose. Other yeasts and bacteria are under investigation to ferment xylose and other pentoses into ethanol.
## Prospective technologies
The anaerobic bacterium Clostridium ljungdahlii, recently discovered in commercial chicken wastes, can produce ethanol from single-carbon sources including synthesis gas, a mixture of carbon monoxide and hydrogen that can be generated from the partial combustion of either fossil fuels or biomass. Use of these bacteria to produce ethanol from synthesis gas has progressed to the pilot plant stage at the BRI Energy facility in Fayetteville, Arkansas.
Another prospective technology is the closed-loop ethanol plant. Ethanol produced from corn has a number of critics who suggest that it is primarily just recycled fossil fuels because of the energy required to grow the grain and convert it into ethanol. However, the closed-loop ethanol plant attempts to address this criticism. In a closed-loop plant, the energy for the distillation comes from fermented manure, produced from cattle that have been fed the by-products from the distillation. The leftover manure is then used to fertilize the soil used to grow the grain. Such a process is expected to have a much lower fossil fuel requirement.
Though in an early stage of research, there is some development of alternative production methods that use feed stocks such as municipal waste or recycled products, rice hulls, sugarcane bagasse, small diameter trees, wood chips, and switchgrass.
## Testing
Breweries and biofuel plants employ two methods for measuring ethanol concentration. Infrared ethanol sensors measure the vibrational frequency of dissolved ethanol using the CH band at 2900 cm−1. This method uses a relatively inexpensive solid state sensor that compares the CH band with a reference band to calculate the ethanol content. The calculation makes use of the Beer-Lambert law. Alternatively, by measuring the density of the starting material and the density of the product, using a hydrometer, the change in specific gravity during fermentation indicates the alcohol content. This inexpensive and indirect method has a long history in the beer brewing industry.
## Purification
Ethylene hydration or brewing produces an ethanol-water mixture. For most industrial and fuel uses, the ethanol must be purified. Fractional distillation can concentrate ethanol to 95.6% by weight (89.5 mole%). This mixture is an azeotrope with a boiling point of 78.1 °C, and cannot be further purified by distillation.
In one common industrial method to obtain absolute alcohol, a small quantity of benzene is added to rectified spirit and the mixture is then distilled. Absolute alcohol is obtained in the third fraction, which distills over at 78.3 °C (351.4 K). Because a small amount of the benzene used remains in the solution, absolute alcohol produced by this method is not suitable for consumption, as benzene is carcinogenic.
There is also an absolute alcohol production process by desiccation using glycerol. Alcohol produced by this method is known as spectroscopic alcohol — so called because the absence of benzene makes it suitable as a solvent in spectroscopy.
Other methods for obtaining absolute ethanol include desiccation using adsorbents such as starch or zeolites, which adsorb water preferentially, as well as azeotropic distillation and extractive distillation.
# Types of ethanol
## Alcoholic beverages
Distilled alcoholic beverages are usually distilled to a high purity and then diluted. However, in some countries such as Poland, rectified spirit (95-96%) is sold directly to the consumer, for human consumption. Also, vodka is rectified spirit diluted to 37.5-60% alcohol by volume.
## Denatured alcohol
Pure ethanol and alcoholic beverages are heavily taxed. Ethanol has many applications that do not involve human consumption. To relieve the tax burden on these application, most jurisdictions waive the tax when agents have been added to the ethanol to render it unfit for human consumption. These include bittering agents such as denatonium benzoate, as well as toxins such as methanol, naphtha, and pyridine.
## Absolute ethanol
Absolute or anhydrous alcohol generally refers to purified ethanol, containing no more than one percent water. Absolute alcohol not intended for human consumption often contains trace amounts of toxic benzene.
Pure ethanol is classed as 200 proof in the USA, equivalent to 175 degrees proof in the (now rarely used) UK system.
## Neutralized ethanol
Ethanol for analytic purposes is said to be neutralized when potassium or sodium hydroxide is added to ethanol containing a pH indicator, such phenolphthalein, until its color begins to turn. The solution can then be used in a titration to determine the pH of a test solution.
# Use
## As a fuel
The largest single use of ethanol is as a motor fuel and fuel additive. The largest national fuel ethanol industries exist in Brazil (gasoline sold in Brazil contains at least 20% ethanol and hydrous ethanol is also used as fuel).
Today, almost half of Brazilian cars are able to use 100% ethanol as fuel, which includes ethanol-only engines and flexible-fuel engines. Flex-fuel engines are able to work with all ethanol, all gasoline, or any mixture of both. Brazil supports this population of ethanol-burning automobiles with large national infrastructure that produces ethanol from domestically grown sugar cane. Sugar cane not only has a greater concentration of sucrose than corn (by about 30%), but is also much easier to extract. The bagasse generated by the process is not wasted, but is utilized in power plants as a surprisingly efficient fuel to produce electricity.
World production of ethanol in 2006 was 51 billion liters, (13.5 billion gallons), with 69% of the world supply coming from Brazil and the United States.
The United States fuel ethanol industry is based largely on maize. According to the Renewable Fuels Association, as of November 2006, 107 grain ethanol biorefineries in the United States have the capacity to produce 5.1 billion gallons of ethanol per year. An additional 56 construction projects underway (in the U.S.) can add 3.8 billion gallons of new capacity in the next 18 months. Over time, it is believed that a material portion of the ~150 billion gallon per year market for gasoline will begin to be replaced with fuel ethanol.
The Energy Policy Act of 2005 requires that 4 billion gallons of "renewable fuel" be used in 2006 and this requirement will grow to a yearly production of 7.5 billion gallons by 2012.
In the United States, ethanol is most commonly blended with gasoline as a 10% ethanol blend nicknamed "gasohol". This blend is widely sold throughout the U.S. Midwest, and in cities required by the 1990 Clean Air Act to oxygenate their gasoline during the winter.
### Controversy
As reported in "The Energy Balance of Corn Ethanol: an Update," the energy returned on energy invested EROEI for ethanol made from corn in the U.S. is 1.34 (it yields 34% more energy than it takes to produce it). Input energy includes natural gas based fertilizers, farm equipment, transformation from corn or other materials, and transportation. However, other researchers report that the production of ethanol consumes more energy than it yields.
Lately criticism and controversy has been growing over the massive subsidies that some companies have been receiving for ethanol production, including "the bulk of the more than $10 billion in subsidies to Archer-Daniels-Midland since 1980," according to the CATO institute. Recent articles have also blamed subsidized ethanol production for the nearly 200% increase in milk prices since 2004, although that is disputed by some.
Oil has historically had a much higher EROEI than agriculturally produced ethanol, especially from petroleum deposits accessible by land, but also from those that only offshore drilling rigs can reach. Apart from this, the amount of ethanol needed to run the United States, for example, is greater than its own farmland could produce, even if fields now used for food were converted for production of non-food-grade corn. It has been estimated that "if every bushel of U.S. corn, wheat, rice and soybean were used to produce ethanol, it would only cover about 4% of U.S. energy needs on a net basis."
In the United States, preferential regulatory and tax treatment of ethanol automotive fuels introduces complexities beyond its energy economics alone. North American automakers have in 2006 and 2007 promoted a blend of 85% ethanol and 15% gasoline, marketed as E85, and their flex-fuel vehicles, e.g. GM's "Live Green, Go Yellow" campaign. The apparent motivation is the nature of U.S. Corporate Average Fuel Economy (CAFE) standards, which give an effective 54% fuel efficiency bonus to vehicles capable of running on 85% alcohol blends over vehicles not adapted to run on 85% alcohol blends. In addition to this auto manufacturer-driven impetus for 85% alcohol blends, the United States Environmental Protection Agency had authority to mandate that minimum proportions of oxygenates be added to automotive gasoline on regional and seasonal bases from 1992 until 2006 in an attempt to reduce air pollution, in particular ground-level ozone and smog. As a consequence, much gasoline sold in the United States is blended with up to 10% of an unspecified oxygenating agent. In America, incidents of methyl tert(iary)-butyl ether (MTBE) groundwater contamination in the majority of the 50 states, and the State of California's ban on the use of MTBE as a gasoline additive has allowed ethanol to displace it as the most common fuel oxygenate.
## Rocket fuel
Ethanol was commonly used as fuel in early bipropellant rocket vehicles, in conjunction with an oxidizer such as liquid oxygen. The German V-2 rocket of World War II, credited with beginning the space age, used ethanol, mixed with water to reduce the combustion chamber temperature. The V-2's design team helped develop U.S. rockets following World War II, including the ethanol-fueled Redstone rocket, which launched the first U.S. satellite. Alcohols fell into general disuse as more efficient rocket fuels were developed.
## Alcoholic beverages
Ethanol is the principal psychoactive constituent in alcoholic beverages, with depressant effects to the central nervous system. It has a complex mode of action and affects multiple systems in the brain. Similar psychoactives include those which also interact with GABA receptors, such as gamma-hydroxybutyric acid.
Alcoholic beverages vary considerably in their ethanol content and in the foodstuffs from which they are produced. Most alcoholic beverages can be broadly classified as fermented beverages, beverages made by the action of yeast on sugary foodstuffs, or as distilled beverages, beverages whose preparation involves concentrating the ethanol in fermented beverages by distillation. The ethanol content of a beverage is usually measured in terms of the volume fraction of ethanol in the beverage, expressed either as a percentage or in alcoholic proof units.
Fermented beverages can be broadly classified by the foodstuff from which they are fermented. Beers are made from cereal grains or other starchy materials, wines and ciders from fruit juices, and meads from honey. Cultures around the world have made fermented beverages from numerous other foodstuffs, and local and national names for various fermented beverages abound.
Distilled beverages are made by distilling fermented beverages. Broad categories of distilled beverages include whiskeys, distilled from fermented cereal grains; brandies, distilled from fermented fruit juices, and rum, distilled from fermented molasses or sugarcane juice. Vodka and similar neutral grain spirits can be distilled from any fermented material (grain or potatoes are most common); these spirits are so thoroughly distilled that no tastes from the particular starting material remain. Numerous other spirits and liqueurs are prepared by infusing flavors from fruits, herbs, and spices into distilled spirits. A traditional example is gin, which is created by infusing juniper berries into a neutral grain alcohol.
In a few beverages, ethanol is concentrated by means other than distillation. Applejack is traditionally made by freeze distillation, by which water is frozen out of fermented apple cider, leaving a more ethanol-rich liquid behind. Eisbier (more commonly, eisbock) is also freeze-distilled, with beer as the base beverage. Fortified wines are prepared by adding brandy or some other distilled spirit to partially-fermented wine. This kills the yeast and conserves some of the sugar in grape juice; such beverages are not only more ethanol-rich, but are often sweeter than other wines.
Alcoholic beverages are sometimes used in cooking, not only for their inherent flavors, but also because the alcohol dissolves hydrophobic flavor compounds which water cannot.
## Feedstock
Ethanol is an important industrial ingredient and has widespread use as a base chemical for other organic compounds. These include ethyl halides, ethyl esters, diethyl ether, acetic acid, butadiene, and ethyl amines.
## Antiseptic use
Ethanol is used in medical wipes and in most common antibacterial hand sanitizer gels at a concentration of about 62% (percentage by weight, not volume) as an antiseptic. Ethanol kills organisms by denaturing their proteins and dissolving their lipids and is effective against most bacteria and fungi, and many viruses, but is ineffective against bacterial spores.
## Antidote
Although ethanol is a poison, it is sometimes used as an antidote for poisoning by other, more toxic alcohols, in particular methanol and ethylene glycol. Ethanol competes with other alcohols for the alcohol dehydrogenase enzyme, preventing metabolism into toxic aldehyde and carboxylic acid derivatives.
## Other uses
- Ethanol is easily soluble in water and is a good solvent. Ethanol is less polar than water and used in perfumes, paints and tinctures.
- Ethanol is also used in design and sketch art markers, such as Copic, and Tria.
# Metabolism and toxicology
Pure ethanol is a tasteless liquid with a strong and distinctive odor that produces a characteristic heat-like sensation when brought into contact with the tongue or mucous membranes. Ethanol adds a distinctive taste to drinks. When applied to open wounds (as for disinfection) it produces a strong stinging sensation. Pure or highly concentrated ethanol may permanently damage living tissue on contact. Ethanol applied to unbroken skin cools the skin rapidly through evaporation.
Ethanol is a central nervous system depressant and has significant psychoactive effects in sublethal doses; for specifics, see effects of alcohol on the body by dose. Based on its abilities to change the human consciousness, ethanol is considered a drug. Death from ethyl alcohol consumption is possible when blood alcohol level reaches 0.4%. A blood level of 0.5% or more is commonly fatal. Levels of even less than 0.1% can cause intoxication, with unconsciousness often occurring at 0.3-0.4%.
In America, about half of the deaths in car accidents occur in alcohol-related crashes. There is no completely safe level of alcohol for driving, since the risk of a fatal car accident rises exponentially with the level of alcohol in the driver's blood. However, most drunk driving laws governing the acceptable levels in the blood while driving or operating heavy machinery set typical upper limits of between 0.05% or 0.08%.
Ethanol interacts in harmful ways with a number of other drugs, including barbiturates, benzodiazepines, narcotics, and phenothiazines
## Metabolism
Ethanol within the human body is converted into acetaldehyde by alcohol dehydrogenase and then into acetic acid by acetaldehyde dehydrogenase. The product of the first step of this breakdown, acetaldehyde, is more toxic than ethanol. Acetaldehyde is linked to most of the clinical effects of alcohol. It has been shown to increase the risk of contracting cirrhosis of the liver, multiple forms of cancer, and alcoholism.
## Magnitude of effect
Some individuals have less effective forms of one or both of these enzymes, and can experience more severe symptoms from ethanol consumption than others. Conversely, those who have acquired ethanol tolerance have a greater quantity of these enzymes, and metabolize ethanol more rapidly.
The amount of ethanol in the body is typically quantified by blood alcohol content (BAC), the milligrams of ethanol per 100 milliliters of blood. The table at right summarizes the symptoms of ethanol consumption. Small doses of ethanol generally produce euphoria and relaxation; people experiencing these symptoms tend to become talkative and less inhibited, and may exhibit poor judgement. At higher dosages (BAC > 100 mg/dl), ethanol acts as a central nervous system depressant, producing at progressively higher dosages, impaired sensory and motor function, slowed cognition, stupefaction, unconsciousness, and possible death.
Frequent use of alcoholic beverages has also been shown to be a major contributing factor in cases of elevated blood levels of triglycerides. | Ethanol
Template:Chembox new
# Overview
Ethanol, also known as ethyl alcohol, drinking alcohol or grain alcohol, is a flammable, colorless, slightly toxic chemical compound, and is best known as the alcohol found in alcoholic beverages. In common usage, it is often referred to simply as alcohol. Its molecular formula is variously represented as EtOH, CH3CH2OH, C2H5OH or as its empirical formula C2H6O (which it shares with dimethyl ether).
After the use of fire, fermentation of sugar into ethanol is perhaps the earliest organic reaction known to humanity, and the intoxicating effects of ethanol consumption have certainly been known since ancient times. In modern times ethanol intended for industrial use has also been produced from byproducts of petroleum refining.
Because of ethanol's ease of production and its low toxicity, it finds widespread use as a solvent for substances intended for human contact or consumption, including scents, flavorings, colorings, and medicines. In chemistry it is both an essential solvent and a fundamental feedstock for the synthesis of other products. Because it burns cleanly, ethanol has a long history as a fuel, including as a fuel for internal combustion engines.
# History
Ethanol has been used by humans since prehistory as the intoxicating ingredient in alcoholic beverages. Dried residues on 9000-year-old pottery found in northern mainland China imply the use of alcoholic beverages even among Neolithic peoples.[1] Its isolation as a relatively pure compound was first achieved by Persian alchemists who developed the art of distillation during the Abbasid caliphate, the most notable of whom was Al-Razi. The writings attributed to Jabir Ibn Hayyan (Geber) (721-815) mention the flammable vapors of boiled wine. Al-Kindī (801-873) unambiguously described the distillation of wine.[2] Absolute ethanol was first obtained in 1796 by Johann Tobias Lowitz, by filtering distilled ethanol through charcoal.
Antoine Lavoisier described ethanol as a compound of carbon, hydrogen, and oxygen, and in 1808, Nicolas-Théodore de Saussure determined ethanol's chemical formula. Fifty years later Archibald Scott Couper published a structural formula for ethanol, which places ethanol among the first of chemical compounds to have its chemical structures determined.[3]
Ethanol was first prepared synthetically in 1826, through the independent efforts of Henry Hennel in Great Britain and S.G. Sérullas in France. Michael Faraday prepared ethanol by the acid-catalyzed hydration of ethylene in 1828, in a process similar to that used for industrial ethanol synthesis today.[4]
Ethanol served as lamp fuel in the United States as early as 1840, although taxes levied during the Civil War on industrial alcohol rendered the practice uneconomical.[5] The tax was not repealed until 1906,[5] and by 1908 ethanol was used to power early Model T automobiles.[6] With the advent of Prohibition in 1920 though, sellers of ethanol fuel were accused of being allies of moonshiners,[5] and ethanol fuel once again faded from the public eye. The recent rise in oil prices has spurred renewed interest.
# Physical properties
The properties of ethanol stem primarily from the presence of its hydroxyl group and the shortness of its carbon chain. Ethanol's hydroxyl group is able to participate in hydrogen bonding, rendering it more viscous and less volatile than less polar organic compounds of similar molecular weight. Ethanol, like most short-chain alcohols, is flammable, colorless, has a strong odor, and is volatile.
Ethanol is slightly more refractive than water with a refractive index of 1.36242 (at λ=589.3 nm and 18.35 °C).[7]
Ethanol is a versatile solvent, miscible in all proportions with water and many organic solvents, including acetic acid, acetone, benzene, carbon tetrachloride, chloroform, diethyl ether, ethylene glycol, glycerol, nitromethane, pyridine, and toluene.[7][8] It is also miscible with light aliphatic hydrocarbons such as pentane and hexane, as well as aliphatic chlorides such as trichloroethane and tetrachloroethylene.[8] Ethanol's miscibility with water is in contrast to longer chain alcohols (five or more carbons), whose water solubility decreases rapidly as the number of carbons increases.[9]
Hydrogen bonding causes pure ethanol to be hygroscopic to the extent that it readily absorbs water from the air. The polar nature of the hydroxyl group causes ethanol to dissolve many ionic compounds, notably sodium and potassium hydroxides, magnesium chloride, calcium chloride, ammonium chloride, ammonium bromide, and sodium bromide.[8] Sodium and potassium chlorides are slightly soluble in ethanol.[8] Because the ethanol molecule also has a nonpolar end, it also dissolves nonpolar substances, including most essential oils,[10] as well as numerous flavoring, coloring, and medicinal agents.
Several unusual phenomena are associated with mixtures of ethanol and water. Ethanol-water mixtures have less volume than their individual components. A mixture of equal volumes ethanol and water has only 95.6% of the volume of equal parts ethanol and water, unmixed (at 15.56 °C).[7] The addition of even a few percent of ethanol to water sharply reduces the surface tension of water. This property partially explains the tears of wine phenomenon. When wine is swirled in a glass, ethanol evaporates quickly from the thin film of wine on the wall of the glass. As its ethanol content decreases, its surface tension increases, and the thin film beads up and runs down the glass in channels rather than as a smooth sheet.
Ethanol and mixtures with water greater than about 50% ethanol are flammable and easily ignited. Ethanol-water solutions below 50% ethanol by volume may also be flammable if the solution is vaporized by heating (as in some cooking methods that call for wine to be added to a hot pan, causing it to flash boil into a vapor, which is then ignited to "burn off" excessive alcohol).
# Chemistry
Ethanol is classified as a primary alcohol, meaning that the carbon to which its hydroxyl group is attached has at least two hydrogen atoms attached to it as well.
The chemistry of ethanol is largely that of its hydroxyl group.
Ethanol's hydroxyl proton is very weakly acidic; it is an even weaker acid than water. Ethanol can be quantitatively converted to its conjugate base, the ethoxide ion (CH3CH2O−), by reaction with an alkali metal such as sodium:[9]
Under special conditions, ethanol reacts with hydrogen halides to produce ethyl halides such as ethyl chloride and ethyl bromide:
HCl reaction requires a catalyst such as zinc chloride.[11]
HBr requires refluxing with a sulfuric acid catalyst.[11]
Ethyl halides can also be produced by reacting ethanol with more specialized halogenating agents, such as thionyl chloride for preparing ethyl chloride, or phosphorus tribromide for preparing ethyl bromide.[9][11]
Under acid-catalyzed conditions, ethanol reacts with carboxylic acids to produce ethyl esters and water:
For this reaction to produce useful yields it is necessary to remove water from the reaction mixture as it is formed.
Ethanol can also form esters with inorganic acids. Diethyl sulfate and triethyl phosphate, prepared by reacting ethanol with sulfuric and phosphoric acid respectively, are both useful ethylating agents in organic synthesis. Ethyl nitrite, prepared from the reaction of ethanol with sodium nitrite and sulfuric acid, was formerly a widely-used diuretic.
Strong acid desiccants, such as sulfuric acid, cause ethanol's dehydration to form either diethyl ether or ethylene:
Which product, diethyl ether or ethylene, predominates depends on the precise reaction conditions.
Ethanol can be oxidized to acetaldehyde, and further oxidized to acetic acid. In the human body, these oxidation reactions are catalyzed by enzymes. In the laboratory, aqueous solutions of strong oxidizing agents, such as chromic acid or potassium permanganate, oxidize ethanol to acetic acid, and it is difficult to stop the reaction at acetaldehyde at high yield. Ethanol can be oxidized to acetaldehyde, without over oxidation to acetic acid, by reacting it with pyridinium chromic chloride.[11]
When exposed to chlorine, ethanol is both oxidized and its alpha carbon chlorinated to form the compound, chloral.
Combustion of ethanol forms carbon dioxide and water:
# Production
Ethanol is produced both as a petrochemical, through the hydration of ethylene, and biologically, by fermenting sugars with yeast.[12] Which process is more economical is dependent upon the prevailing prices of petroleum and of grain feed stocks.
## Ethylene hydration
Ethanol for use as industrial feedstock is most often made from petrochemical feed stocks, typically by the acid-catalyzed hydration of ethylene, represented by the chemical equation
The catalyst is most commonly phosphoric acid,[13] adsorbed onto a porous support such as diatomaceous earth or charcoal. This catalyst was first used for large-scale ethanol production by the Shell Oil Company in 1947.[14] The reaction is carried out at with an excess of high pressure steam at 300 °C.
In an older process, first practiced on the industrial scale in 1930 by Union Carbide,[15] but now almost entirely obsolete, ethylene was hydrated indirectly by reacting it with concentrated sulfuric acid to produce ethyl sulfate, which was then hydrolyzed to yield ethanol and regenerate the sulfuric acid:[11]
## Fermentation
Ethanol for use in alcoholic beverages, and the vast majority of ethanol for use as fuel, is produced by fermentation. When certain species of yeast, most importantly, Saccharomyces cerevisiae, metabolize sugar in the absence of oxygen, they produce ethanol and carbon dioxide. The chemical equation below summarizes the conversion:
The process of culturing yeast under conditions to produce alcohol is called as brewing. Ethanol's toxicity to yeast limits the ethanol concentration obtainable by brewing. The most ethanol-tolerant strains of yeast can survive up to approximately 15% ethanol by volume.[16]
The fermentation process must exclude oxygen. If oxygen is present, yeast undergo aerobic respiration which produces carbon dioxide and water rather than ethanol.
In order to produce ethanol from starchy materials such as cereal grains, the starch must first be converted into sugars. In brewing beer, this has traditionally been accomplished by allowing the grain to germinate, or malt, which produces the enzyme, amylase. When the malted grain is mashed, the amylase converts the remaining starches into sugars. For fuel ethanol, the hydrolysis of starch into glucose can be accomplished more rapidly by treatment with dilute sulfuric acid, fungally produced amylase, or some combination of the two.[17]
## Cellulosic ethanol
Sugars for ethanol fermentation can be obtained from cellulose. Until recently, however, the cost of the cellulase enzymes capable of hydrolyzing cellulose has been prohibitive. The Canadian firm, Iogen, brought the first cellulose-based ethanol plant on-stream in 2004.[18] Its primary consumer so far has been the Canadian government, which, along with the United States Department of Energy, has invested heavily in the commercialization of cellulosic ethanol. Deployment of this technology could turn a number of cellulose-containing agricultural byproducts, such as corncobs, straw, and sawdust, into renewable energy resources. Other enzyme companies are developing genetically engineered fungi that produce large volumes of cellulase, xylanase and hemicellulase enzymes. These would convert agricultural residues such as corn stover, wheat straw and sugar cane bagasse and energy crops such as switchgrass into fermentable sugars.[19]
Cellulose-bearing materials typically also contain other polysaccharides, including hemicellulose. When hydrolyzed, hemicellulose decomposes into mostly five-carbon sugars such as xylose. S. cerevisiae, the yeast most commonly used for ethanol production, cannot metabolize xylose. Other yeasts and bacteria are under investigation to ferment xylose and other pentoses into ethanol.[20]
## Prospective technologies
The anaerobic bacterium Clostridium ljungdahlii, recently discovered in commercial chicken wastes, can produce ethanol from single-carbon sources including synthesis gas, a mixture of carbon monoxide and hydrogen that can be generated from the partial combustion of either fossil fuels or biomass. Use of these bacteria to produce ethanol from synthesis gas has progressed to the pilot plant stage at the BRI Energy facility in Fayetteville, Arkansas.[21]
Another prospective technology is the closed-loop ethanol plant.[22] Ethanol produced from corn has a number of critics who suggest that it is primarily just recycled fossil fuels because of the energy required to grow the grain and convert it into ethanol. However, the closed-loop ethanol plant attempts to address this criticism. In a closed-loop plant, the energy for the distillation comes from fermented manure, produced from cattle that have been fed the by-products from the distillation. The leftover manure is then used to fertilize the soil used to grow the grain. Such a process is expected to have a much lower fossil fuel requirement.[23]
Though in an early stage of research, there is some development of alternative production methods that use feed stocks such as municipal waste or recycled products, rice hulls, sugarcane bagasse, small diameter trees, wood chips, and switchgrass.[24]
## Testing
Breweries and biofuel plants employ two methods for measuring ethanol concentration. Infrared ethanol sensors measure the vibrational frequency of dissolved ethanol using the CH band at 2900 cm−1. This method uses a relatively inexpensive solid state sensor that compares the CH band with a reference band to calculate the ethanol content. The calculation makes use of the Beer-Lambert law. Alternatively, by measuring the density of the starting material and the density of the product, using a hydrometer, the change in specific gravity during fermentation indicates the alcohol content. This inexpensive and indirect method has a long history in the beer brewing industry.
## Purification
Ethylene hydration or brewing produces an ethanol-water mixture. For most industrial and fuel uses, the ethanol must be purified. Fractional distillation can concentrate ethanol to 95.6% by weight (89.5 mole%). This mixture is an azeotrope with a boiling point of 78.1 °C, and cannot be further purified by distillation.
In one common industrial method to obtain absolute alcohol, a small quantity of benzene is added to rectified spirit and the mixture is then distilled. Absolute alcohol is obtained in the third fraction, which distills over at 78.3 °C (351.4 K).[9] Because a small amount of the benzene used remains in the solution, absolute alcohol produced by this method is not suitable for consumption, as benzene is carcinogenic.[25]
There is also an absolute alcohol production process by desiccation using glycerol. Alcohol produced by this method is known as spectroscopic alcohol — so called because the absence of benzene makes it suitable as a solvent in spectroscopy.
Other methods for obtaining absolute ethanol include desiccation using adsorbents such as starch or zeolites, which adsorb water preferentially, as well as azeotropic distillation and extractive distillation.
# Types of ethanol
## Alcoholic beverages
Distilled alcoholic beverages are usually distilled to a high purity and then diluted. However, in some countries such as Poland, rectified spirit (95-96%) is sold directly to the consumer, for human consumption.[26] Also, vodka is rectified spirit diluted to 37.5-60% alcohol by volume.
## Denatured alcohol
Pure ethanol and alcoholic beverages are heavily taxed. Ethanol has many applications that do not involve human consumption. To relieve the tax burden on these application, most jurisdictions waive the tax when agents have been added to the ethanol to render it unfit for human consumption. These include bittering agents such as denatonium benzoate, as well as toxins such as methanol, naphtha, and pyridine.[27][28]
## Absolute ethanol
Absolute or anhydrous alcohol generally refers to purified ethanol, containing no more than one percent water. Absolute alcohol not intended for human consumption often contains trace amounts of toxic benzene.
Pure ethanol is classed as 200 proof in the USA, equivalent to 175 degrees proof in the (now rarely used) UK system.
## Neutralized ethanol
Ethanol for analytic purposes is said to be neutralized when potassium or sodium hydroxide is added to ethanol containing a pH indicator, such phenolphthalein, until its color begins to turn. The solution can then be used in a titration to determine the pH of a test solution.
# Use
## As a fuel
The largest single use of ethanol is as a motor fuel and fuel additive. The largest national fuel ethanol industries exist in Brazil (gasoline sold in Brazil contains at least 20% ethanol and hydrous ethanol is also used as fuel).[32]
Today, almost half of Brazilian cars are able to use 100% ethanol as fuel, which includes ethanol-only engines and flexible-fuel engines. Flex-fuel engines are able to work with all ethanol, all gasoline, or any mixture of both. Brazil supports this population of ethanol-burning automobiles with large national infrastructure that produces ethanol from domestically grown sugar cane. Sugar cane not only has a greater concentration of sucrose than corn (by about 30%), but is also much easier to extract. The bagasse generated by the process is not wasted, but is utilized in power plants as a surprisingly efficient fuel to produce electricity.
World production of ethanol in 2006 was 51 billion liters, (13.5 billion gallons), with 69% of the world supply coming from Brazil and the United States.[33]
The United States fuel ethanol industry is based largely on maize. According to the Renewable Fuels Association, as of November 2006, 107 grain ethanol biorefineries in the United States have the capacity to produce 5.1 billion gallons of ethanol per year. An additional 56 construction projects underway (in the U.S.) can add 3.8 billion gallons of new capacity in the next 18 months. Over time, it is believed that a material portion of the ~150 billion gallon per year market for gasoline will begin to be replaced with fuel ethanol.[34]
The Energy Policy Act of 2005 requires that 4 billion gallons of "renewable fuel" be used in 2006 and this requirement will grow to a yearly production of 7.5 billion gallons by 2012.[35]
In the United States, ethanol is most commonly blended with gasoline as a 10% ethanol blend nicknamed "gasohol". This blend is widely sold throughout the U.S. Midwest, and in cities required by the 1990 Clean Air Act to oxygenate their gasoline during the winter.
### Controversy
As reported in "The Energy Balance of Corn Ethanol: an Update,"[36] the energy returned on energy invested EROEI for ethanol made from corn in the U.S. is 1.34 (it yields 34% more energy than it takes to produce it). Input energy includes natural gas based fertilizers, farm equipment, transformation from corn or other materials, and transportation. However, other researchers report that the production of ethanol consumes more energy than it yields.[37][38]
Lately criticism and controversy has been growing over the massive subsidies that some companies have been receiving for ethanol production,[39] including "the bulk of the more than $10 billion in subsidies to Archer-Daniels-Midland since 1980," according to the CATO institute.[40] Recent articles have also blamed subsidized ethanol production for the nearly 200% increase in milk prices since 2004,[41] although that is disputed by some.
Oil has historically had a much higher EROEI than agriculturally produced ethanol, especially from petroleum deposits accessible by land, but also from those that only offshore drilling rigs can reach. Apart from this, the amount of ethanol needed to run the United States, for example, is greater than its own farmland could produce, even if fields now used for food were converted for production of non-food-grade corn. It has been estimated that "if every bushel of U.S. corn, wheat, rice and soybean were used to produce ethanol, it would only cover about 4% of U.S. energy needs on a net basis."[42]
In the United States, preferential regulatory and tax treatment of ethanol automotive fuels introduces complexities beyond its energy economics alone. North American automakers have in 2006 and 2007 promoted a blend of 85% ethanol and 15% gasoline, marketed as E85, and their flex-fuel vehicles, e.g. GM's "Live Green, Go Yellow" campaign.[43] The apparent motivation is the nature of U.S. Corporate Average Fuel Economy (CAFE) standards, which give an effective 54% fuel efficiency bonus to vehicles capable of running on 85% alcohol blends over vehicles not adapted to run on 85% alcohol blends.[44] In addition to this auto manufacturer-driven impetus for 85% alcohol blends, the United States Environmental Protection Agency had authority to mandate that minimum proportions of oxygenates be added to automotive gasoline on regional and seasonal bases from 1992 until 2006 in an attempt to reduce air pollution, in particular ground-level ozone and smog.[45] As a consequence, much gasoline sold in the United States is blended with up to 10% of an unspecified oxygenating agent.[46] In America, incidents of methyl tert(iary)-butyl ether (MTBE) groundwater contamination in the majority of the 50 states,[47] and the State of California's ban on the use of MTBE as a gasoline additive has allowed ethanol to displace it as the most common fuel oxygenate.[48]
## Rocket fuel
Ethanol was commonly used as fuel in early bipropellant rocket vehicles, in conjunction with an oxidizer such as liquid oxygen. The German V-2 rocket of World War II, credited with beginning the space age, used ethanol, mixed with water to reduce the combustion chamber temperature.[49][50] The V-2's design team helped develop U.S. rockets following World War II, including the ethanol-fueled Redstone rocket, which launched the first U.S. satellite.[51] Alcohols fell into general disuse as more efficient rocket fuels were developed.[50]
## Alcoholic beverages
Ethanol is the principal psychoactive constituent in alcoholic beverages, with depressant effects to the central nervous system. It has a complex mode of action and affects multiple systems in the brain.[52] Similar psychoactives include those which also interact with GABA receptors, such as gamma-hydroxybutyric acid.[53]
Alcoholic beverages vary considerably in their ethanol content and in the foodstuffs from which they are produced. Most alcoholic beverages can be broadly classified as fermented beverages, beverages made by the action of yeast on sugary foodstuffs, or as distilled beverages, beverages whose preparation involves concentrating the ethanol in fermented beverages by distillation. The ethanol content of a beverage is usually measured in terms of the volume fraction of ethanol in the beverage, expressed either as a percentage or in alcoholic proof units.
Fermented beverages can be broadly classified by the foodstuff from which they are fermented. Beers are made from cereal grains or other starchy materials, wines and ciders from fruit juices, and meads from honey. Cultures around the world have made fermented beverages from numerous other foodstuffs, and local and national names for various fermented beverages abound.
Distilled beverages are made by distilling fermented beverages. Broad categories of distilled beverages include whiskeys, distilled from fermented cereal grains; brandies, distilled from fermented fruit juices, and rum, distilled from fermented molasses or sugarcane juice. Vodka and similar neutral grain spirits can be distilled from any fermented material (grain or potatoes are most common); these spirits are so thoroughly distilled that no tastes from the particular starting material remain. Numerous other spirits and liqueurs are prepared by infusing flavors from fruits, herbs, and spices into distilled spirits. A traditional example is gin, which is created by infusing juniper berries into a neutral grain alcohol.
In a few beverages, ethanol is concentrated by means other than distillation. Applejack is traditionally made by freeze distillation, by which water is frozen out of fermented apple cider, leaving a more ethanol-rich liquid behind. Eisbier (more commonly, eisbock) is also freeze-distilled, with beer as the base beverage. Fortified wines are prepared by adding brandy or some other distilled spirit to partially-fermented wine. This kills the yeast and conserves some of the sugar in grape juice; such beverages are not only more ethanol-rich, but are often sweeter than other wines.
Alcoholic beverages are sometimes used in cooking, not only for their inherent flavors, but also because the alcohol dissolves hydrophobic flavor compounds which water cannot.
## Feedstock
Ethanol is an important industrial ingredient and has widespread use as a base chemical for other organic compounds. These include ethyl halides, ethyl esters, diethyl ether, acetic acid, butadiene, and ethyl amines.
## Antiseptic use
Ethanol is used in medical wipes and in most common antibacterial hand sanitizer gels at a concentration of about 62% (percentage by weight, not volume) as an antiseptic. Ethanol kills organisms by denaturing their proteins and dissolving their lipids and is effective against most bacteria and fungi, and many viruses, but is ineffective against bacterial spores.[54]
## Antidote
Although ethanol is a poison, it is sometimes used as an antidote for poisoning by other, more toxic alcohols, in particular methanol[55] and ethylene glycol. Ethanol competes with other alcohols for the alcohol dehydrogenase enzyme, preventing metabolism into toxic aldehyde and carboxylic acid derivatives.[56]
## Other uses
- Ethanol is easily soluble in water and is a good solvent. Ethanol is less polar than water and used in perfumes, paints and tinctures.
- Ethanol is also used in design and sketch art markers, such as Copic, and Tria.
# Metabolism and toxicology
Pure ethanol is a tasteless liquid with a strong and distinctive odor that produces a characteristic heat-like sensation when brought into contact with the tongue or mucous membranes. Ethanol adds a distinctive taste to drinks. When applied to open wounds (as for disinfection) it produces a strong stinging sensation. Pure or highly concentrated ethanol may permanently damage living tissue on contact. Ethanol applied to unbroken skin cools the skin rapidly through evaporation.
Ethanol is a central nervous system depressant and has significant psychoactive effects in sublethal doses; for specifics, see effects of alcohol on the body by dose. Based on its abilities to change the human consciousness, ethanol is considered a drug.[58] Death from ethyl alcohol consumption is possible when blood alcohol level reaches 0.4%. A blood level of 0.5% or more is commonly fatal. Levels of even less than 0.1% can cause intoxication, with unconsciousness often occurring at 0.3-0.4%.[59]
In America, about half of the deaths in car accidents occur in alcohol-related crashes.[60] There is no completely safe level of alcohol for driving, since the risk of a fatal car accident rises exponentially with the level of alcohol in the driver's blood.[61] However, most drunk driving laws governing the acceptable levels in the blood while driving or operating heavy machinery set typical upper limits of between 0.05% or 0.08%.
Ethanol interacts in harmful ways with a number of other drugs, including barbiturates, benzodiazepines, narcotics, and phenothiazines[59]
## Metabolism
Ethanol within the human body is converted into acetaldehyde by alcohol dehydrogenase and then into acetic acid by acetaldehyde dehydrogenase. The product of the first step of this breakdown, acetaldehyde,[62] is more toxic than ethanol. Acetaldehyde is linked to most of the clinical effects of alcohol. It has been shown to increase the risk of contracting cirrhosis of the liver,[53] multiple forms of cancer, and alcoholism.
## Magnitude of effect
Some individuals have less effective forms of one or both of these enzymes, and can experience more severe symptoms from ethanol consumption than others. Conversely, those who have acquired ethanol tolerance have a greater quantity of these enzymes, and metabolize ethanol more rapidly.[63]
The amount of ethanol in the body is typically quantified by blood alcohol content (BAC), the milligrams of ethanol per 100 milliliters of blood. The table at right summarizes the symptoms of ethanol consumption. Small doses of ethanol generally produce euphoria and relaxation; people experiencing these symptoms tend to become talkative and less inhibited, and may exhibit poor judgement. At higher dosages (BAC > 100 mg/dl), ethanol acts as a central nervous system depressant, producing at progressively higher dosages, impaired sensory and motor function, slowed cognition, stupefaction, unconsciousness, and possible death.
Frequent use of alcoholic beverages has also been shown to be a major contributing factor in cases of elevated blood levels of triglycerides.[64] | https://www.wikidoc.org/index.php/Alcohol_ethyl | |
cb3cae2c16e27d3e91d0915bee609a2204406c22 | wikidoc | Pentose | Pentose
# Overview
A pentose is a monosaccharide with five carbon atoms.
They either have an aldehyde functional group in position 1 (aldopentoses), or a ketone functional group in position 2 (ketopentoses).
The aldopentoses have three chiral centres ("asymmetric carbon atoms") and so 8 different stereoisomers are possible.
The 4 D-aldopentoses are:
A mnemonic suggested that can be used to remember the four D-aldopentoses is "ribs are extra lean."
The ketopentoses have 2 chiral centres and therefore 4 possible stereoisomers — ribulose (L- and D-form) and xylulose (L- and D-form).
The D-isomers of both are known to occur naturally as is the L-isomer of xylulose:
The aldehyde and ketone functional groups in these carbohydrates react with neighbouring hydroxyl functional groups to form intramolecular hemiacetals or hemiketals, respectively. The resulting ring structure is related to furan, and is termed a furanose. The ring spontaneously opens and closes, allowing rotation to occur about the bond between the carbonyl group and the neighbouring carbon atom — yielding two distinct configurations (α and β). This process is termed mutarotation.
Ribose is a constituent of RNA, and the related deoxyribose of DNA. | Pentose
# Overview
A pentose is a monosaccharide with five carbon atoms.
They either have an aldehyde functional group in position 1 (aldopentoses), or a ketone functional group in position 2 (ketopentoses).
The aldopentoses have three chiral centres ("asymmetric carbon atoms") and so 8 different stereoisomers are possible.
The 4 D-aldopentoses are:
A mnemonic suggested that can be used to remember the four D-aldopentoses is "ribs are extra lean."
The ketopentoses have 2 chiral centres and therefore 4 possible stereoisomers — ribulose (L- and D-form) and xylulose (L- and D-form).
The D-isomers of both are known to occur naturally as is the L-isomer of xylulose:
The aldehyde and ketone functional groups in these carbohydrates react with neighbouring hydroxyl functional groups to form intramolecular hemiacetals or hemiketals, respectively. The resulting ring structure is related to furan, and is termed a furanose. The ring spontaneously opens and closes, allowing rotation to occur about the bond between the carbonyl group and the neighbouring carbon atom — yielding two distinct configurations (α and β). This process is termed mutarotation.
Ribose is a constituent of RNA, and the related deoxyribose of DNA. | https://www.wikidoc.org/index.php/Aldopentose | |
272e52e0b706d60d6b5c462c16c63d2077f95f46 | wikidoc | Alfalfa | Alfalfa
Alfalfa (Medicago sativa) is a flowering plant in the pea family Fabaceae cultivated as an important forage crop. In the UK it is known as lucerne and Lucerne grass in India.
Alfalfa is a cool season perennial legume living from three to twelve years, depending on variety and climate. It resembles clover with clusters of small purple flowers. The plant grows to a height of up to 1 metre (3 ft), and has a deep root system sometimes stretching to 4.5 metres (15 ft). This makes it very resilient, especially to droughts. It has a tetraploid genome. The plant exhibits autotoxicity, which means that it is difficult for alfalfa seed to grow in existing stands of alfalfa. Therefore, it is recommended that alfalfa fields be rotated with other species (e.g. corn, wheat) before reseeding.
Like other legumes, its root nodules contain bacteria, Sinorhizobium meliloti, with the ability to fix nitrogen, producing a high-protein feed regardless of available nitrogen in the soil. Its nitrogen-fixing abilities (which increases soil nitrogen) and use as animal feed greatly improved agricultural efficiency. (The nitrogen comes from the air, which is 78 percent molecular nitrogen.)
Alfalfa is widely grown throughout the world as forage for cattle, and is most often harvested as hay, but can also be made into silage, grazed, or fed as greenchop. Alfalfa has the highest feeding value of all common hay crops, being used less frequently as pasture. When grown on soils where it is well-adapted, alfalfa is the highest yielding forage plant.
Alfalfa is one of the most important legumes used in agriculture. The US is the largest alfalfa producer in the world, but considerable area is found in Argentina (primarily grazed), Australia, South Africa, and the Middle East. Known as Kuthirai Masal in Tamil, alfalfa is mostly grown in the Coimbatore district of Tamil Nadu, southern India.
The leading alfalfa growing states (within the U.S.A.) are California, South Dakota, and Wisconsin. The upper Midwestern states account for about 50% of US production, the Northeastern states 10%, the Western states 40% and the Southeastern states almost none. Alfalfa has a wide range of adaptation and can be grown from very cold northern plains to high mountain valleys, from rich temperate agricultural regions to Mediterranean climates and searing hot deserts.
Its primary use is as feed for dairy cattle, and secondarily for beef cattle, horses, sheep, and goats. Humans also eat alfalfa sprouts, in salads and sandwiches, for example. Tender shoots are eaten in some places as a leaf vegetable. Human consumption of fresh mature plant parts is rare and limited primarily by alfalfa's high fiber content. Dehydrated alfalfa leaf is commercially available as a dietary supplement in several forms, such as tablets, powders and tea. Alfalfa is believed by some to be a galactagogue, a substance that induces lactation.
# Culture
Alfalfa can be sown in spring or fall, and does best on well-drained soils with a neutral pH of 6.8 – 7.5. Alfalfa requires a great deal of potassium. Alfalfa is moderately sensitive to salt levels in both the soil and irrigation water, although it continues to be grown in the arid southwest, where salinity is an emerging issue. Soils low in fertility should be fertilized with manure or a chemical fertilizer, but correction of pH is particularly important. Usually a seeding rate of 13 – 20 kg/hectare (12 – 25 lb/acre) is recommended, with differences based upon region, soil type, and seeding method. A nurse crop is sometimes used, particularly for spring plantings, to reduce weed problems. Herbicides are sometimes used instead, particularly in Western production.
In most climates, alfalfa is cut three to four times a year but is harvested up to 12 times per year in Arizona and Southern California. Total yields are typically around 8 tonnes per hectare (4 short tons per acre) but yields have been recorded up to 20 t/ha (16 short tons per acre). Yields vary with region, weather, and the crop's stage of maturity when cut. Later cuttings improve yield but reduce nutritional content.
Alfalfa is considered an 'insectary' due to the large number of insects it attracts. Some pests such as Alfalfa weevil, aphids, armyworms, and the potato leafhopper can reduce alfalfa yields dramatically, particularly with the second cutting when weather is warmest. Chemical controls are sometimes used to prevent this. Alfalfa is also susceptible to root rots including phytophora, rhizoctonia, and Texas Root Rot.
Alfalfa seed production requires the presence of pollinators when the fields of alfalfa are in bloom. Alfalfa pollination is somewhat problematic, however, because the pollen-carrying keel of the flower trips and strikes pollinating bees on the head to help transfer the pollen to the foraging bee. Western honey bees do not like being struck in the head repeatedly and learn to defeat this action by drawing nectar from the side of the flower. The bees thus collect the nectar but carry no pollen and so do not pollenate the next flower they visit. Because older, experienced bees don't pollinate alfalfa well, most pollination is accomplished by young bees that have not yet learned the trick of robbing the flower without tripping the head-knocking keel. When western honey bees are used to pollinate alfalfa, the beekeeper stocks the field at a very high rate to maximize the number of young bees.
Today the alfalfa leafcutter bee is increasingly used to circumvent this problem. As a solitary but gregarious bee species, it does not build colonies or store honey, but is a very efficient pollinator of alfalfa flowers. Nesting is in individual tunnels in wooden or plastic material, supplied by the alfalfa seed growers. The leafcutter bees are used in the Pacific Northwest, while western honeybees dominate in California alfalfa seed production.
A smaller amount of alfalfa produced for seed is pollinated by the alkali bee, mostly in the northwestern USA. It is cultured in special beds near the fields. These bees also have their own problems. They are not portable like honey bees; and when fields are planted in new areas, the bees take several seasons to build up. Honey bees are still trucked to many of the fields at bloom time.
# Harvesting
When alfalfa is to be used as hay, it is usually cut and baled. Loose haystacks are still used in some areas, but bales are easier to transport and store. Ideally, the hay is cut just as the field is beginning to flower. When using farm equipment rather than hand-harvesting, a swather cuts the alfalfa and arranges it in windrows. In areas where the alfalfa does not immediately dry out on its own, a machine know as a mower-conditioner is used to cut the hay. The mower-conditioner has a set of rollers or flails that crimp and break the stems as they pass through the mower, making the alfalfa dry faster. After the alfalfa has dried, a tractor pulling a baler collects the hay into bales.
There are several types of bales commonly used for alfalfa. For small animals and individual horses, the alfalfa is baled into small "square" bales — actually rectangular, and typically about 40 x 45 x 100 cm (14 in x 18 in x 38 in). Small square bales weigh from 25 – 30 kg (50 – 70 pounds) depending on moisture, and can be easily hand separated into "flakes". Cattle ranches use large round bales, typically 1.4 to 1.8 m (4 to 6 feet) in diameter and weighing from 500 to 1,000 kg, (1000 to 2000 lbs). These bales can be placed in stable stacks or in large feeders for herds of horses, or unrolled on the ground for large herds of cattle. The bales can be loaded and stacked with a tractor using a spike, known as a bale spear, that pierces the center of the bale. Or they can be handled with a grapple (claw) on the tractor's front-end loader. A more recent innovation is large "square" bales, roughly the same proportions as the small squares, but much larger. The bale size was set so that stacks would fit perfectly on a large flatbed truck. These are more common in western states.
When used as feed for dairy cattle alfalfa is often made into haylage by a process known as ensiling. Rather than drying it to make dry hay, the alfalfa is chopped finely and fermented in silos, trenches, or bags, anywhere where the oxygen supply can be limited to promote fermentation. Fermenting the alfalfa allows it to retain high nutrient levels similar to those of fresh forage, and is also more palatable to dairy cattle than dry hay.
# Varieties
Considerable research and development has been done with this important plant. Older cultivars such as 'Vernal' have been the standard for years, but many better public and private varieties are now available and better adapted to particular climates. Private companies release many new varieties each year in the US.
Most varieties go dormant in the fall, with reduced growth in response to low temperatures and shorter days. 'Non-dormant' varieties that grow through the winter are planted in long-seasoned environments such as Mexico, Arizona, and Southern California, whereas 'dormant' varieties are planted in the Upper Midwest, Canada, and the Northeast. 'Non-dormant' varieties can be higher yielding, but they are susceptible to winter-kill in cold climates and have poorer persistence.
Most alfalfa cultivars contain genetic material from Sickle Medick (M. falcata), a wild variety of alfalfa that naturally hybridizes with M. sativa to produce Sand Lucerne (M. sativa ssp. varia). This species may bear either the purple flowers of alfalfa or the yellow of sickle medick, and is so called for its ready growth in sandy soil.
Most of the improvements in alfalfa over the last decades have consisted of better disease resistance on poorly drained soils in wet years, better ability to overwinter in cold climates, and the production of more leaves. Multileaf alfalfa varieties have more than three leaflets per leaf, giving them greater nutritional content by weight because there is more leafy matter for the same amount of stem.
Modern alfalfa varieties have probably a wider range of insect, disease, and nematode resistance than many other agricultural species. The North American Alfalfa Improvement Conference records new varieties and encourages communication between breeders.
Roundup Ready alfalfa is a genetically modified variety, patented by Monsanto, that is resistant to Monsanto's glyphosate herbicide Roundup. Although most broadleaf plants, including ordinary alfalfa, are sensitive to Roundup, growers can spray fields of Roundup Ready alfalfa with Roundup, and so kill the weeds without harming the alfalfa crop. Roundup Ready alfalfa was sold in the United States from 2005-2007 and more than 300,000 acres (Expression error: Missing operand for *. ) were planted with it, out of 21,000,000 acres (Expression error: Missing operand for *. ). However, in May 2007, the California Northern District Court issued an injunction order prohibiting farmers from planting Roundup Ready alfalfa until the US Department of Agriculture (USDA) completed a study on the genetically engineered crop's likely environmental impact. In response, the USDA put a hold on any further planting of Roundup Ready alfalfa. The key issues of the lawsuit were the possibility that Roundup Resistance could be transmitted to other plants, including both other crops and weeds, making major pest species resistant to an important herbicide, Roundup.
# Phytoestrogens in alfalfa
Alfalfa, like other leguminous crops, is a known source of phytoestrogens. Grazing on alfalfa has been suspected as a cause of reduced fertility in sheep.
# Medical Uses
Alfalfa has been used as an herbal medicine for over 1,500 years. Alfalfa is high in protein, calcium, plus other minerals, vitamin A, vitamins in the B group, vitamin C, vitamin D, vitamin E, and vitamin K.
## Traditional Uses
In early Chinese medicines, physicians used young alfalfa leaves to treat disorders related to the digestive tract and the kidneys. In India, ayurvedic physicians used the leaves for treating poor digestion. They made a cooling poultice from the seeds for boils. At the time, alfalfa was also believed to be helpful towards people suffering from arthritis and water retention.
## Modern Use
It is majorly used in homeopathic medicines worldwide. Today, alfalfa is suggested for treating anemia, diabetes, to extend appetite and contribute towards weight gain, as a diuretic for increased urination, for indigestion and bladder disorders, alfalfa can also be used as an estrogen replacement in order to increase breast milk and to mitigate premenstrual syndrome, a dietary supplement, and to lower blood cholestrol levels.
# Use in Organic Gardening
Alfalfa is commonly used as plant fertilizer in the form of granular pellets. Alfalfa is also used to make Alfalfa tea, which contains Triacontanol, a plant growth stimulant.
# Literary references
- In Of Mice and Men, the popular novella authored by John Steinbeck, Lenny becomes increasingly obsessed with growing Alfalfa for his rabbits for if he ever gets a farm with George.
- In Catch-22 by Joseph Heller, Major Major Major Major's father receives a government subsidy for every strip of ground he does not grow alfalfa on. He uses this money to buy more land to not grow alfalfa on. | Alfalfa
Alfalfa (Medicago sativa) is a flowering plant in the pea family Fabaceae cultivated as an important forage crop. In the UK it is known as lucerne and Lucerne grass in India.
Alfalfa is a cool season perennial legume living from three to twelve years, depending on variety and climate. It resembles clover with clusters of small purple flowers. The plant grows to a height of up to 1 metre (3 ft), and has a deep root system sometimes stretching to 4.5 metres (15 ft). This makes it very resilient, especially to droughts. It has a tetraploid genome. The plant exhibits autotoxicity, which means that it is difficult for alfalfa seed to grow in existing stands of alfalfa. Therefore, it is recommended that alfalfa fields be rotated with other species (e.g. corn, wheat) before reseeding.
Like other legumes, its root nodules contain bacteria, Sinorhizobium meliloti, with the ability to fix nitrogen, producing a high-protein feed regardless of available nitrogen in the soil. Its nitrogen-fixing abilities (which increases soil nitrogen) and use as animal feed greatly improved agricultural efficiency. (The nitrogen comes from the air, which is 78 percent molecular nitrogen.)
Alfalfa is widely grown throughout the world as forage for cattle, and is most often harvested as hay, but can also be made into silage, grazed, or fed as greenchop. Alfalfa has the highest feeding value of all common hay crops, being used less frequently as pasture. When grown on soils where it is well-adapted, alfalfa is the highest yielding forage plant.
Alfalfa is one of the most important legumes used in agriculture. The US is the largest alfalfa producer in the world, but considerable area is found in Argentina (primarily grazed), Australia, South Africa, and the Middle East. Known as Kuthirai Masal in Tamil, alfalfa is mostly grown in the Coimbatore district of Tamil Nadu, southern India.
The leading alfalfa growing states (within the U.S.A.) are California, South Dakota, and Wisconsin. The upper Midwestern states account for about 50% of US production, the Northeastern states 10%, the Western states 40% and the Southeastern states almost none. Alfalfa has a wide range of adaptation and can be grown from very cold northern plains to high mountain valleys, from rich temperate agricultural regions to Mediterranean climates and searing hot deserts.
Its primary use is as feed for dairy cattle, and secondarily for beef cattle, horses, sheep, and goats. Humans also eat alfalfa sprouts, in salads and sandwiches, for example. Tender shoots are eaten in some places as a leaf vegetable. Human consumption of fresh mature plant parts is rare and limited primarily by alfalfa's high fiber content. Dehydrated alfalfa leaf is commercially available as a dietary supplement in several forms, such as tablets, powders and tea. Alfalfa is believed by some to be a galactagogue, a substance that induces lactation.
# Culture
Alfalfa can be sown in spring or fall, and does best on well-drained soils with a neutral pH of 6.8 – 7.5. Alfalfa requires a great deal of potassium. Alfalfa is moderately sensitive to salt levels in both the soil and irrigation water, although it continues to be grown in the arid southwest, where salinity is an emerging issue. Soils low in fertility should be fertilized with manure or a chemical fertilizer, but correction of pH is particularly important. Usually a seeding rate of 13 – 20 kg/hectare (12 – 25 lb/acre) is recommended, with differences based upon region, soil type, and seeding method. A nurse crop is sometimes used, particularly for spring plantings, to reduce weed problems. Herbicides are sometimes used instead, particularly in Western production.
In most climates, alfalfa is cut three to four times a year but is harvested up to 12 times per year in Arizona and Southern California. Total yields are typically around 8 tonnes per hectare (4 short tons per acre) but yields have been recorded up to 20 t/ha (16 short tons per acre). Yields vary with region, weather, and the crop's stage of maturity when cut. Later cuttings improve yield but reduce nutritional content.
Alfalfa is considered an 'insectary' due to the large number of insects it attracts. Some pests such as Alfalfa weevil, aphids, armyworms, and the potato leafhopper can reduce alfalfa yields dramatically, particularly with the second cutting when weather is warmest. Chemical controls are sometimes used to prevent this. Alfalfa is also susceptible to root rots including phytophora, rhizoctonia, and Texas Root Rot.
Alfalfa seed production requires the presence of pollinators when the fields of alfalfa are in bloom. Alfalfa pollination is somewhat problematic, however, because the pollen-carrying keel of the flower trips and strikes pollinating bees on the head to help transfer the pollen to the foraging bee. Western honey bees do not like being struck in the head repeatedly and learn to defeat this action by drawing nectar from the side of the flower. The bees thus collect the nectar but carry no pollen and so do not pollenate the next flower they visit.[2] Because older, experienced bees don't pollinate alfalfa well, most pollination is accomplished by young bees that have not yet learned the trick of robbing the flower without tripping the head-knocking keel. When western honey bees are used to pollinate alfalfa, the beekeeper stocks the field at a very high rate to maximize the number of young bees.
Today the alfalfa leafcutter bee is increasingly used to circumvent this problem. As a solitary but gregarious bee species, it does not build colonies or store honey, but is a very efficient pollinator of alfalfa flowers. Nesting is in individual tunnels in wooden or plastic material, supplied by the alfalfa seed growers.[2] The leafcutter bees are used in the Pacific Northwest, while western honeybees dominate in California alfalfa seed production.
A smaller amount of alfalfa produced for seed is pollinated by the alkali bee, mostly in the northwestern USA. It is cultured in special beds near the fields. These bees also have their own problems. They are not portable like honey bees; and when fields are planted in new areas, the bees take several seasons to build up.[2] Honey bees are still trucked to many of the fields at bloom time.
# Harvesting
When alfalfa is to be used as hay, it is usually cut and baled. Loose haystacks are still used in some areas, but bales are easier to transport and store. Ideally, the hay is cut just as the field is beginning to flower. When using farm equipment rather than hand-harvesting, a swather cuts the alfalfa and arranges it in windrows. In areas where the alfalfa does not immediately dry out on its own, a machine know as a mower-conditioner is used to cut the hay. The mower-conditioner has a set of rollers or flails that crimp and break the stems as they pass through the mower, making the alfalfa dry faster. After the alfalfa has dried, a tractor pulling a baler collects the hay into bales.
There are several types of bales commonly used for alfalfa. For small animals and individual horses, the alfalfa is baled into small "square" bales — actually rectangular, and typically about 40 x 45 x 100 cm (14 in x 18 in x 38 in). Small square bales weigh from 25 – 30 kg (50 – 70 pounds) depending on moisture, and can be easily hand separated into "flakes". Cattle ranches use large round bales, typically 1.4 to 1.8 m (4 to 6 feet) in diameter and weighing from 500 to 1,000 kg, (1000 to 2000 lbs). These bales can be placed in stable stacks or in large feeders for herds of horses, or unrolled on the ground for large herds of cattle. The bales can be loaded and stacked with a tractor using a spike, known as a bale spear, that pierces the center of the bale. Or they can be handled with a grapple (claw) on the tractor's front-end loader. A more recent innovation is large "square" bales, roughly the same proportions as the small squares, but much larger. The bale size was set so that stacks would fit perfectly on a large flatbed truck. These are more common in western states.
When used as feed for dairy cattle alfalfa is often made into haylage by a process known as ensiling. Rather than drying it to make dry hay, the alfalfa is chopped finely and fermented in silos, trenches, or bags, anywhere where the oxygen supply can be limited to promote fermentation. Fermenting the alfalfa allows it to retain high nutrient levels similar to those of fresh forage, and is also more palatable to dairy cattle than dry hay.
# Varieties
Considerable research and development has been done with this important plant. Older cultivars such as 'Vernal' have been the standard for years, but many better public and private varieties are now available and better adapted to particular climates. Private companies release many new varieties each year in the US.
Most varieties go dormant in the fall, with reduced growth in response to low temperatures and shorter days. 'Non-dormant' varieties that grow through the winter are planted in long-seasoned environments such as Mexico, Arizona, and Southern California, whereas 'dormant' varieties are planted in the Upper Midwest, Canada, and the Northeast. 'Non-dormant' varieties can be higher yielding, but they are susceptible to winter-kill in cold climates and have poorer persistence.
Most alfalfa cultivars contain genetic material from Sickle Medick (M. falcata), a wild variety of alfalfa that naturally hybridizes with M. sativa to produce Sand Lucerne (M. sativa ssp. varia). This species may bear either the purple flowers of alfalfa or the yellow of sickle medick, and is so called for its ready growth in sandy soil.
Most of the improvements in alfalfa over the last decades have consisted of better disease resistance on poorly drained soils in wet years, better ability to overwinter in cold climates, and the production of more leaves. Multileaf alfalfa varieties have more than three leaflets per leaf, giving them greater nutritional content by weight because there is more leafy matter for the same amount of stem.
Modern alfalfa varieties have probably a wider range of insect, disease, and nematode resistance than many other agricultural species. The North American Alfalfa Improvement Conference records new varieties and encourages communication between breeders.
Roundup Ready alfalfa is a genetically modified variety, patented by Monsanto, that is resistant to Monsanto's glyphosate herbicide Roundup. Although most broadleaf plants, including ordinary alfalfa, are sensitive to Roundup, growers can spray fields of Roundup Ready alfalfa with Roundup, and so kill the weeds without harming the alfalfa crop. Roundup Ready alfalfa was sold in the United States from 2005-2007 and more than 300,000 acres (Expression error: Missing operand for *. ) were planted with it, out of 21,000,000 acres (Expression error: Missing operand for *. ). However, in May 2007, the California Northern District Court issued an injunction order prohibiting farmers from planting Roundup Ready alfalfa until the US Department of Agriculture (USDA) completed a study on the genetically engineered crop's likely environmental impact. In response, the USDA put a hold on any further planting of Roundup Ready alfalfa. The key issues of the lawsuit were the possibility that Roundup Resistance could be transmitted to other plants, including both other crops and weeds, making major pest species resistant to an important herbicide, Roundup.
# Phytoestrogens in alfalfa
Alfalfa, like other leguminous crops, is a known source of phytoestrogens.[3] Grazing on alfalfa has been suspected as a cause of reduced fertility in sheep.
# Medical Uses
Alfalfa has been used as an herbal medicine for over 1,500 years. Alfalfa is high in protein, calcium, plus other minerals, vitamin A, vitamins in the B group, vitamin C, vitamin D, vitamin E, and vitamin K.
## Traditional Uses
In early Chinese medicines, physicians used young alfalfa leaves to treat disorders related to the digestive tract and the kidneys. In India, ayurvedic physicians used the leaves for treating poor digestion. They made a cooling poultice from the seeds for boils. At the time, alfalfa was also believed to be helpful towards people suffering from arthritis and water retention.
## Modern Use
It is majorly used in homeopathic medicines worldwide. Today, alfalfa is suggested for treating anemia, diabetes, to extend appetite and contribute towards weight gain, as a diuretic for increased urination, for indigestion and bladder disorders, alfalfa can also be used as an estrogen replacement in order to increase breast milk and to mitigate premenstrual syndrome, a dietary supplement, and to lower blood cholestrol levels.[4]
# Use in Organic Gardening
Alfalfa is commonly used as plant fertilizer in the form of granular pellets. Alfalfa is also used to make Alfalfa tea, which contains Triacontanol, a plant growth stimulant.
# Literary references
- In Of Mice and Men, the popular novella authored by John Steinbeck, Lenny becomes increasingly obsessed with growing Alfalfa for his rabbits for if he ever gets a farm with George.
- In Catch-22 by Joseph Heller, Major Major Major Major's father receives a government subsidy for every strip of ground he does not grow alfalfa on. He uses this money to buy more land to not grow alfalfa on. | https://www.wikidoc.org/index.php/Alfalfa | |
98da7a0f7fb793916d2317b29e8dd67345e29f44 | wikidoc | Algarot | Algarot
Algarot, is a white emetic powder formerly used in alchemy that consists of a compound of trichloride and trioxide of antimony. It was used as an emetic because it purges violently both upwards and downwards.
# Alternative names
Algarot is also known as mercurius vitæ ("mercury of life"), emetic powder, powder of algaroth, algarel, antimonious oxychloride, or antimony hypochlorite.
# Synthesis
Historically, algarot was prepared of butter of antimony (antimony trichloride), which was no more than the regulus of that mineral, dissolved in acids, and separated again by means of several lotions with lukewarm water, which absorbed those acids. By collecting all the lotions and evaporating two third parts, what remained was a very acid liquor, called "Spirit of Philosophical Vitriol".
At present, algarot is synthesised by exposing antimony trichloride to water, like so: | Algarot
Template:Chembox new
Algarot, is a white emetic powder formerly used in alchemy that consists of a compound of trichloride and trioxide of antimony. It was used as an emetic because it purges violently both upwards and downwards.
# Alternative names
Algarot is also known as mercurius vitæ ("mercury of life"), emetic powder, powder of algaroth, algarel, antimonious oxychloride, or antimony hypochlorite.
# Synthesis
Historically, algarot was prepared of butter of antimony (antimony trichloride), which was no more than the regulus of that mineral, dissolved in acids, and separated again by means of several lotions with lukewarm water, which absorbed those acids. By collecting all the lotions and evaporating two third parts, what remained was a very acid liquor, called "Spirit of Philosophical Vitriol".
At present, algarot is synthesised by exposing antimony trichloride to water, like so: | https://www.wikidoc.org/index.php/Algarot | |
4a918e19244cd52a4a82f50d4eabc248fea5e072 | wikidoc | Algebra | Algebra
Algebra is a branch of mathematics concerning the study of structure, relation and quantity. The name is derived from the treatise written by the Persian mathematician, astronomer, astrologer and geographer, ] titled Kitab al-Jabr wa-l-Muqabala (meaning "The Compendious Book on Calculation by Completion and Balancing"), which provided symbolic operations for the systematic solution of linear and quadratic equations. Al-Khwarizimi's book made its way to Europe and was translated into Latin as Ludus algebrae et almucgrabalaeque. The title was eventually shortened to "algabra."
Together with geometry, analysis, combinatorics, and number theory, algebra is one of the main branches of mathematics. Elementary algebra is often part of the curriculum in secondary education and provides an introduction to the basic ideas of algebra, including effects of adding and multiplying numbers, the concept of variables, definition of polynomials, along with factorization and determining their roots.
Algebra is much broader than elementary algebra and can be generalized. In addition to working directly with numbers, algebra covers working with symbols, variables, and set elements. Addition and multiplication are viewed as general operations, and their precise definitions lead to structures such as groups, rings and fields.
# Classification
Algebra may be divided roughly into the following categories:
- Elementary algebra, in which the properties of operations on the real number system are recorded using symbols as "place holders" to denote constants and variables, and the rules governing mathematical expressions and equations involving these symbols are studied (note that this usually includes the subject matter of courses called intermediate algebra and college algebra), also called second year and third year algebra;
- Abstract algebra, sometimes also called modern algebra, in which algebraic structures such as groups, rings and fields are axiomatically defined and investigated; this includes, among other fields,
- Linear algebra, in which the specific properties of vector spaces are studied (including matrices);
- Universal algebra, in which properties common to all algebraic structures are studied.
- Algebraic number theory, in which the properties of numbers are studied through algebraic systems. Number theory inspired much of the original abstraction in algebra.
- Algebraic geometry in its algebraic aspect.
- Algebraic combinatorics, in which abstract algebraic methods are used to study combinatorial questions.
In some directions of advanced study, axiomatic algebraic systems such as groups, rings, fields, and algebras over a field are investigated in the presence of a geometric structure (a metric or a topology) which is compatible with the algebraic structure. The list includes a number of areas of functional analysis:
- Normed linear spaces
- Banach spaces
- Hilbert spaces
- Banach algebras
- Normed algebras
- Topological algebras
- Topological groups
# Elementary algebra
Elementary algebra is the most basic form of algebra. It is taught to students who are presumed to have no knowledge of mathematics beyond the basic principles of arithmetic. In arithmetic, only numbers and their arithmetical operations (such as +, −, ×, ÷) occur. In algebra, numbers are often denoted by symbols (such as a, x, or y). This is useful because:
- It allows the general formulation of arithmetical laws (such as a + b = b + a for all a and b), and thus is the first step to a systematic exploration of the properties of the real number system.
- It allows the reference to "unknown" numbers, the formulation of equations and the study of how to solve these (for instance, "Find a number x such that 3x + 1 = 10").
- It allows the formulation of functional relationships (such as "If you sell x tickets, then your profit will be 3x - 10 dollars, or f(x) = 3x - 10, where f is the function, and x is the number to which the function is applied.").
## Polynomials
A polynomial is an expression that is constructed from one or more variables and constants, using only the operations of addition, subtraction, and multiplication (where repeated multiplication of the same variable is standardly denoted as exponentiation with a constant positive whole number exponent). For example, x^2 + 2x -3\, is a polynomial in the single variable x.
An important class of problems in algebra is factorization of polynomials, that is, expressing a given polynomial as a product of other polynomials. The example polynomial above can be factored as (x-1)(x+3)\,\!. A related class of problems is finding algebraic expressions for the roots of a polynomial in a single variable.
# Abstract algebra
Abstract algebra extends the familiar concepts found in elementary algebra and arithmetic of numbers to more general concepts.
Sets: Rather than just considering the different types of numbers, abstract algebra deals with the more general concept of sets: a collection of all objects (called elements) selected by property, specific for the set. All collections of the familiar types of numbers are sets. Other examples of sets include the set of all two-by-two matrices, the set of all second-degree polynomials (ax2 + bx + c), the set of all two dimensional vectors in the plane, and the various finite groups such as the cyclic groups which are the group of integers modulo n. Set theory is a branch of logic and not technically a branch of algebra.
Binary operations: The notion of addition (+) is abstracted to give a binary operation, - say. The notion of binary operation is meaningless without the set on which the operation is defined. For two elements a and b in a set S a*b gives another element in the set; this condition is called closure. Addition (+), subtraction (-), multiplication (×), and division (÷) can be binary operations when defined on different sets, as is addition and multiplication of matrices, vectors, and polynomials.
Identity elements: The numbers zero and one are abstracted to give the notion of an identity element for an operation. Zero is the identity element for addition and one is the identity element for multiplication. For a general binary operator - the identity element e must satisfy a - e = a and e - a = a. This holds for addition as a + 0 = a and 0 + a = a and multiplication a × 1 = a and 1 × a = a. However, if we take the positive natural numbers and addition, there is no identity element.
Inverse elements: The negative numbers give rise to the concept of inverse elements. For addition, the inverse of a is -a, and for multiplication the inverse is 1/a. A general inverse element a-1 must satisfy the property that a - a-1 = e and a-1 - a = e.
Associativity: Addition of integers has a property called associativity. That is, the grouping of the numbers to be added does not affect the sum. For example: (2+3)+4=2+(3+4). In general, this becomes (a - b) - c = a - (b - c). This property is shared by most binary operations, but not subtraction or division or octonion multiplication.
Commutativity: Addition of integers also has a property called commutativity. That is, the order of the numbers to be added does not affect the sum. For example: 2+3=3+2. In general, this becomes a - b = b - a. Only some binary operations have this property. It holds for the integers with addition and multiplication, but it does not hold for matrix multiplication or quaternion multiplication .
## Groups—structures of a set with a single binary operation
Combining the above concepts gives one of the most important structures in mathematics: a group. A group is a combination of a set S and a single binary operation '*', defined in any way you choose, but with the following properties:
- An identity element e exists, such that for every member a of S, e - a and a - e are both identical to a.
- Every element has an inverse: for every member a of S, there exists a member a-1 such that a - a-1 and a-1 - a are both identical to the identity element.
- The operation is associative: if a, b and c are members of S, then (a - b) - c is identical to a - (b - c).
If a group is also commutative - that is, for any two members a and b of S, a - b is identical to b - a – then the group is said to be Abelian.
For example, the set of integers under the operation of addition is a group. In this group, the identity element is 0 and the inverse of any element a is its negation, -a. The associativity requirement is met, because for any integers a, b and c, (a + b) + c = a + (b + c)
The nonzero rational numbers form a group under multiplication. Here, the identity element is 1, since 1 × a = a × 1 = a for any rational number a. The inverse of a is 1/a, since a × 1/a = 1.
The integers under the multiplication operation, however, do not form a group. This is because, in general, the multiplicative inverse of an integer is not an integer. For example, 4 is an integer, but its multiplicative inverse is 1/4, which is not an integer.
The theory of groups is studied in group theory. A major result in this theory is the classification of finite simple groups, mostly published between about 1955 and 1983, which is thought to classify all of the finite simple groups into roughly 30 basic types.
Semigroups, quasigroups, and monoids are structures similar to groups, but more general. They comprise a set and a closed binary operation, but do not necessarily satisfy the other conditions. A semigroup has an associative binary operation, but might not have an identity element. A monoid is a semigroup which does have an identity but might not have an inverse for every element. A quasigroup satisfies a requirement that any element can be turned into any other by a unique pre- or post-operation; however the binary operation might not be associative. All are instance of groupoids, structures with a binary operation upon which no further conditions are imposed.
All groups are monoids, and all monoids are semigroups.
## Rings and fields—structures of a set with two particular binary operations, (+) and (×)
Groups just have one binary operation. To fully explain the behaviour of the different types of numbers, structures with two operators need to be studied. The most important of these are rings, and fields.
Distributivity generalised the distributive law for numbers, and specifies the order in which the operators should be applied, (called the precedence). For the integers (a + b) × c = a×c+ b×c and c × (a + b) = c×a + c×b, and × is said to be distributive over +.
A ring has two binary operations (+) and (×), with × distributive over +. Under the first operator (+) it forms an Abelian group. Under the second operator (×) it is associative, but it does not need to have identity, or inverse, so division is not allowed. The additive (+) identity element is written as 0 and the additive inverse of a is written as −a.
The integers are an example of a ring. The integers have additional properties which make it an integral domain.
A field is a ring with the additional property that all the elements excluding 0 form an Abelian group under ×. The multiplicative (×) identity is written as 1 and the multiplicative inverse of a is written as a-1.
The rational numbers, the real numbers and the complex numbers are all examples of fields.
# Objects called algebras
The word algebra is also used for various algebraic structures:
- Algebra over a field or more generally Algebra over a ring
- Algebra over a set
- Boolean algebra
- F-algebra and F-coalgebra in category theory
- Sigma-algebra
# History
The origins of algebra can be traced to the ancient Babylonians, who developed an advanced arithmetical system with which they were able to do calculations in an algebraic fashion. With the use of this system they were able to apply formulas and calculate solutions for unknown values for a class of problems typically solved today by using linear equations, quadratic equations, and indeterminate linear equations. By contrast, most Egyptians of this era, and most Indian, Greek and Chinese mathematicians in the first millennium BC, usually solved such equations by geometric methods, such as those described in the Rhind Mathematical Papyrus, Sulba Sutras, Euclid's Elements, and The Nine Chapters on the Mathematical Art. The geometric work of the Greeks, typified in the Elements, provided the framework for generalizing formulae beyond the solution of particular problems into more general systems of stating and solving equations.
Later, the Indian mathematicians developed algebraic methods to a high degree of sophistication. Although Diophantus and the Babylonians used mostly special ad hoc methods to solve equations, Brahmagupta was the first to solve equations using general methods. He solved the linear indeterminate equations, quadratic equations, second order indeterminate equations and equations with multiple variable.
The word "algebra" is named after the Arabic word "al-jabr" from the title of the book Template:Unicode, meaning The book of Summary Concerning Calculating by Transposition and Reduction, a book written by the Persian mathematician Template:Unicode in 820. The word Al-Jabr means "reunion". The Hellenistic mathematician Diophantus has traditionally been known as "the father of algebra" but debate now exists as to whether or not Al-Khwarizmi should take that title. Those who support Al-Khwarizmi point to the fact that much of his work on reduction is still in use today and that he gave an exhaustive explanation of solving quadratic equations. Those who support Diophantus point to the fact that the algebra found in Al-Jabr is more elementary than the algebra found in Arithmetica and that Arithmetica is syncopated while Al-Jabr is fully rhetorical. Another Persian mathematician, Omar Khayyam, developed algebraic geometry and found the general geometric solution of the cubic equation. The Indian mathematicians Mahavira and Bhaskara II, and the Chinese mathematician Zhu Shijie, solved various cases of cubic, quartic, quintic and higher-order polynomial equations.
Another key event in the further development of algebra was the general algebraic solution of the cubic and quartic equations, developed in the mid-16th century. The idea of a determinant was developed by Japanese mathematician Kowa Seki in the 17th century, followed by Gottfried Leibniz ten years later, for the purpose of solving systems of simultaneous linear equations using matrices. Gabriel Cramer also did some work on matrices and determinants in the 18th century. Abstract algebra was developed in the 19th century, initially focusing on what is now called Galois theory, and on constructibility issues.
The stages of the development of symbolic algebra are roughly as follows:
- Rhetorical algebra, which was developed by the Babylonians and remained dominant up to the 16th century;
- Geometric constructive algebra, which was emphasised by the Vedic Indian and classical Greek mathematicians;
- Syncopated algebra, as developed by Diophantus, Brahmagupta and the Bakhshali Manuscript; and
- Symbolic algebra, which was initiated by Abū al-Hasan ibn Alī al-Qalasādī and sees its culmination in the work of Gottfried Leibniz.
A timeline of key algebraic developments are as follows:
- Circa 1800 BC: The Old Babylonian Strassburg tablet seeks the solution of a quadratic elliptic equation.
- Circa 1600 BC: The Plimpton 322 tablet gives a table of Pythagorean triples in Babylonian Cuneiform script.
- Circa 800 BC: Indian mathematician Baudhayana, in his Baudhayana Sulba Sutra, discovers Pythagorean triples algebraically, finds geometric solutions of linear equations and quadratic equations of the forms ax2 = c and ax2 + bx = c, and finds two sets of positive integral solutions to a set of simultaneous Diophantine equations.
- Circa 600 BC: Indian mathematician Apastamba, in his Apastamba Sulba Sutra, solves the general linear equation and uses simultaneous Diophantine equations with up to five unknowns.
- Circa 300 BC: In Book II of his Elements, Euclid gives a geometric construction with Euclidean tools for the solution of the quadratic equation for positive real roots. The construction is due to the Pythagorean School of geometry.
- Circa 300 BC: A geometric construction for the solution of the cubic is sought (doubling the cube problem). It is now well known that the general cubic has no such solution using Euclidean tools.
- Circa 100 BC: Algebraic equations are treated in the Chinese mathematics book Jiuzhang suanshu (The Nine Chapters on the Mathematical Art), which contains solutions of linear equations solved using the rule of double false position, geometric solutions of quadratic equations, and the solutions of matrices equivalent to the modern method, to solve systems of simultaneous linear equations.
- Circa 100 BC: The Bakhshali Manuscript written in ancient India uses a form of algebraic notation using letters of the alphabet and other signs, and contains cubic and quartic equations, algebraic solutions of linear equations with up to five unknowns, the general algebraic formula for the quadratic equation, and solutions of indeterminate quadratic equations and simultaneous equations.
- Circa 150 AD: Hero of Alexandria treats algebraic equations in three volumes of mathematics.
- Circa 200: Diophantus, who lived in Egypt and is often considered the "father of algebra", writes his famous Arithmetica, a work featuring solutions of algebraic equations and on the theory of numbers.
- 499: Indian mathematician Aryabhata, in his treatise Aryabhatiya, obtains whole-number solutions to linear equations by a method equivalent to the modern one, describes the general integral solution of the indeterminate linear equation and gives integral solutions of simultaneous indeterminate linear equations.
- Circa 625: Chinese mathematician Wang Xiaotong finds numerical solutions of cubic equations.
- 628: Indian mathematician Brahmagupta, in his treatise Brahma Sputa Siddhanta, invents the chakravala method of solving indeterminate quadratic equations, including Pell's equation, and gives rules for solving linear and quadratic equations.
- 820: The word algebra is derived from operations described in the treatise written by the Persian mathematician Template:Unicode titled Al-Kitab al-Jabr wa-l-Muqabala (meaning "The Compendious Book on Calculation by Completion and Balancing") on the systematic solution of linear and quadratic equations. Al-Khwarizmi is often considered as the "father of algebra", much of whose works on reduction was included in the book and added to many methods we have in algebra now.
- Circa 850: Persian mathematician al-Mahani conceived the idea of reducing geometrical problems such as duplicating the cube to problems in algebra.
- Circa 850: Indian mathematician Mahavira solves various quadratic, cubic, quartic, quintic and higher-order equations, as well as indeterminate quadratic, cubic and higher-order equations.
- Circa 990: Persian Abu Bakr al-Karaji, in his treatise al-Fakhri, further develops algebra by extending Al-Khwarizmi's methodology to incorporate integral powers and integral roots of unknown quantities. He replaces geometrical operations of algebra with modern arithmetical operations, and defines the monomials x, x2, x3, ... and 1/x, 1/x2, 1/x3, ... and gives rules for the products of any two of these.
- Circa 1050: Chinese mathematician Jia Xian finds numerical solutions of polynomial equations.
- 1072: Persian mathematician Omar Khayyam develops algebraic geometry and, in the Treatise on Demonstration of Problems of Algebra, gives a complete classification of cubic equations with general geometric solutions found by means of intersecting conic sections.
- 1114: Indian mathematician Bhaskara, in his Bijaganita (Algebra), recognizes that a positive number has both a positive and negative square root, and solves various cubic, quartic and higher-order polynomial equations, as well as the general quadratic indeterminant equation.
- 1202: Algebra is introduced to Europe largely through the work of Leonardo Fibonacci of Pisa in his work Liber Abaci.
- Circa 1300: Chinese mathematician Zhu Shijie deals with polynomial algebra, solves quadratic equations, simultaneous equations and equations with up to four unknowns, and numerically solves some quartic, quintic and higher-order polynomial equations.
- Circa 1400: Indian mathematician Madhava of Sangamagramma finds iterative methods for approximate solution of non-linear equations.
- Circa 1450: Arab mathematician Abū al-Hasan ibn Alī al-Qalasādī took "the first steps toward the introduction of algebraic symbolism." He represented mathematical symbols using characters from the Arabic alphabet.
- 1535: Nicolo Fontana Tartaglia and others mathematicians in Italy independently solved the general cubic equation.
- 1545: Girolamo Cardano publishes Ars magna -The great art which gives Fontana's solution to the general quartic equation.
- 1572: Rafael Bombelli recognizes the complex roots of the cubic and improves current notation.
- 1591: Francois Viete develops improved symbolic notation for various powers of an unknown and uses vowels for unknowns and consonants for constants in In artem analyticam isagoge.
- 1631: Thomas Harriot in a posthumous publication uses exponential notation and is the first to use symbols to indicate "less than" and "greater than".
- 1682: Gottfried Wilhelm Leibniz develops his notion of symbolic manipulation with formal rules which he calls characteristica generalis.
- 1680s: Japanese mathematician Kowa Seki, in his Method of solving the dissimulated problems, discovers the determinant, and Bernoulli numbers.
- 1750: Gabriel Cramer, in his treatise Introduction to the analysis of algebraic curves, states Cramer's rule and studies algebraic curves, matrices and determinants.
- 1824: Niels Henrik Abel proved that the general quintic equation is insoluble by radicals.
- 1832: Galois theory is developed by Évariste Galois in his work on abstract algebra. | Algebra
Template:Otheruses4
Algebra is a branch of mathematics concerning the study of structure, relation and quantity. The name is derived from the treatise written by the Persian[1] mathematician, astronomer, astrologer and geographer, [[Muhammad ibn Mūsā al-Khwārizmī|Template:Unicode]] titled Kitab al-Jabr wa-l-Muqabala (meaning "The Compendious Book on Calculation by Completion and Balancing"), which provided symbolic operations for the systematic solution of linear and quadratic equations. Al-Khwarizimi's book made its way to Europe and was translated into Latin as Ludus algebrae et almucgrabalaeque. The title was eventually shortened to "algabra."
Together with geometry, analysis, combinatorics, and number theory, algebra is one of the main branches of mathematics. Elementary algebra is often part of the curriculum in secondary education and provides an introduction to the basic ideas of algebra, including effects of adding and multiplying numbers, the concept of variables, definition of polynomials, along with factorization and determining their roots.
Algebra is much broader than elementary algebra and can be generalized. In addition to working directly with numbers, algebra covers working with symbols, variables, and set elements. Addition and multiplication are viewed as general operations, and their precise definitions lead to structures such as groups, rings and fields.
# Classification
Algebra may be divided roughly into the following categories:
- Elementary algebra, in which the properties of operations on the real number system are recorded using symbols as "place holders" to denote constants and variables, and the rules governing mathematical expressions and equations involving these symbols are studied (note that this usually includes the subject matter of courses called intermediate algebra and college algebra), also called second year and third year algebra;
- Abstract algebra, sometimes also called modern algebra, in which algebraic structures such as groups, rings and fields are axiomatically defined and investigated; this includes, among other fields,
- Linear algebra, in which the specific properties of vector spaces are studied (including matrices);
- Universal algebra, in which properties common to all algebraic structures are studied.
- Algebraic number theory, in which the properties of numbers are studied through algebraic systems. Number theory inspired much of the original abstraction in algebra.
- Algebraic geometry in its algebraic aspect.
- Algebraic combinatorics, in which abstract algebraic methods are used to study combinatorial questions.
In some directions of advanced study, axiomatic algebraic systems such as groups, rings, fields, and algebras over a field are investigated in the presence of a geometric structure (a metric or a topology) which is compatible with the algebraic structure. The list includes a number of areas of functional analysis:
- Normed linear spaces
- Banach spaces
- Hilbert spaces
- Banach algebras
- Normed algebras
- Topological algebras
- Topological groups
# Elementary algebra
Elementary algebra is the most basic form of algebra. It is taught to students who are presumed to have no knowledge of mathematics beyond the basic principles of arithmetic. In arithmetic, only numbers and their arithmetical operations (such as +, −, ×, ÷) occur. In algebra, numbers are often denoted by symbols (such as a, x, or y). This is useful because:
- It allows the general formulation of arithmetical laws (such as a + b = b + a for all a and b), and thus is the first step to a systematic exploration of the properties of the real number system.
- It allows the reference to "unknown" numbers, the formulation of equations and the study of how to solve these (for instance, "Find a number x such that 3x + 1 = 10").
- It allows the formulation of functional relationships (such as "If you sell x tickets, then your profit will be 3x - 10 dollars, or f(x) = 3x - 10, where f is the function, and x is the number to which the function is applied.").
## Polynomials
A polynomial is an expression that is constructed from one or more variables and constants, using only the operations of addition, subtraction, and multiplication (where repeated multiplication of the same variable is standardly denoted as exponentiation with a constant positive whole number exponent). For example, <math>x^2 + 2x -3\,</math> is a polynomial in the single variable x.
An important class of problems in algebra is factorization of polynomials, that is, expressing a given polynomial as a product of other polynomials. The example polynomial above can be factored as <math>(x-1)(x+3)\,\!.</math> A related class of problems is finding algebraic expressions for the roots of a polynomial in a single variable.
# Abstract algebra
Abstract algebra extends the familiar concepts found in elementary algebra and arithmetic of numbers to more general concepts.
Sets: Rather than just considering the different types of numbers, abstract algebra deals with the more general concept of sets: a collection of all objects (called elements) selected by property, specific for the set. All collections of the familiar types of numbers are sets. Other examples of sets include the set of all two-by-two matrices, the set of all second-degree polynomials (ax2 + bx + c), the set of all two dimensional vectors in the plane, and the various finite groups such as the cyclic groups which are the group of integers modulo n. Set theory is a branch of logic and not technically a branch of algebra.
Binary operations: The notion of addition (+) is abstracted to give a binary operation, * say. The notion of binary operation is meaningless without the set on which the operation is defined. For two elements a and b in a set S a*b gives another element in the set; this condition is called closure. Addition (+), subtraction (-), multiplication (×), and division (÷) can be binary operations when defined on different sets, as is addition and multiplication of matrices, vectors, and polynomials.
Identity elements: The numbers zero and one are abstracted to give the notion of an identity element for an operation. Zero is the identity element for addition and one is the identity element for multiplication. For a general binary operator * the identity element e must satisfy a * e = a and e * a = a. This holds for addition as a + 0 = a and 0 + a = a and multiplication a × 1 = a and 1 × a = a. However, if we take the positive natural numbers and addition, there is no identity element.
Inverse elements: The negative numbers give rise to the concept of inverse elements. For addition, the inverse of a is -a, and for multiplication the inverse is 1/a. A general inverse element a-1 must satisfy the property that a * a-1 = e and a-1 * a = e.
Associativity: Addition of integers has a property called associativity. That is, the grouping of the numbers to be added does not affect the sum. For example: (2+3)+4=2+(3+4). In general, this becomes (a * b) * c = a * (b * c). This property is shared by most binary operations, but not subtraction or division or octonion multiplication.
Commutativity: Addition of integers also has a property called commutativity. That is, the order of the numbers to be added does not affect the sum. For example: 2+3=3+2. In general, this becomes a * b = b * a. Only some binary operations have this property. It holds for the integers with addition and multiplication, but it does not hold for matrix multiplication or quaternion multiplication .
## Groups—structures of a set with a single binary operation
Combining the above concepts gives one of the most important structures in mathematics: a group. A group is a combination of a set S and a single binary operation '*', defined in any way you choose, but with the following properties:
- An identity element e exists, such that for every member a of S, e * a and a * e are both identical to a.
- Every element has an inverse: for every member a of S, there exists a member a-1 such that a * a-1 and a-1 * a are both identical to the identity element.
- The operation is associative: if a, b and c are members of S, then (a * b) * c is identical to a * (b * c).
If a group is also commutative - that is, for any two members a and b of S, a * b is identical to b * a – then the group is said to be Abelian.
For example, the set of integers under the operation of addition is a group. In this group, the identity element is 0 and the inverse of any element a is its negation, -a. The associativity requirement is met, because for any integers a, b and c, (a + b) + c = a + (b + c)
The nonzero rational numbers form a group under multiplication. Here, the identity element is 1, since 1 × a = a × 1 = a for any rational number a. The inverse of a is 1/a, since a × 1/a = 1.
The integers under the multiplication operation, however, do not form a group. This is because, in general, the multiplicative inverse of an integer is not an integer. For example, 4 is an integer, but its multiplicative inverse is 1/4, which is not an integer.
The theory of groups is studied in group theory. A major result in this theory is the classification of finite simple groups, mostly published between about 1955 and 1983, which is thought to classify all of the finite simple groups into roughly 30 basic types.
Semigroups, quasigroups, and monoids are structures similar to groups, but more general. They comprise a set and a closed binary operation, but do not necessarily satisfy the other conditions. A semigroup has an associative binary operation, but might not have an identity element. A monoid is a semigroup which does have an identity but might not have an inverse for every element. A quasigroup satisfies a requirement that any element can be turned into any other by a unique pre- or post-operation; however the binary operation might not be associative. All are instance of groupoids, structures with a binary operation upon which no further conditions are imposed.
All groups are monoids, and all monoids are semigroups.
## Rings and fields—structures of a set with two particular binary operations, (+) and (×)
Groups just have one binary operation. To fully explain the behaviour of the different types of numbers, structures with two operators need to be studied. The most important of these are rings, and fields.
Distributivity generalised the distributive law for numbers, and specifies the order in which the operators should be applied, (called the precedence). For the integers (a + b) × c = a×c+ b×c and c × (a + b) = c×a + c×b, and × is said to be distributive over +.
A ring has two binary operations (+) and (×), with × distributive over +. Under the first operator (+) it forms an Abelian group. Under the second operator (×) it is associative, but it does not need to have identity, or inverse, so division is not allowed. The additive (+) identity element is written as 0 and the additive inverse of a is written as −a.
The integers are an example of a ring. The integers have additional properties which make it an integral domain.
A field is a ring with the additional property that all the elements excluding 0 form an Abelian group under ×. The multiplicative (×) identity is written as 1 and the multiplicative inverse of a is written as a-1.
The rational numbers, the real numbers and the complex numbers are all examples of fields.
# Objects called algebras
The word algebra is also used for various algebraic structures:
- Algebra over a field or more generally Algebra over a ring
- Algebra over a set
- Boolean algebra
- F-algebra and F-coalgebra in category theory
- Sigma-algebra
# History
The origins of algebra can be traced to the ancient Babylonians,[2] who developed an advanced arithmetical system with which they were able to do calculations in an algebraic fashion. With the use of this system they were able to apply formulas and calculate solutions for unknown values for a class of problems typically solved today by using linear equations, quadratic equations, and indeterminate linear equations. By contrast, most Egyptians of this era, and most Indian, Greek and Chinese mathematicians in the first millennium BC, usually solved such equations by geometric methods, such as those described in the Rhind Mathematical Papyrus, Sulba Sutras, Euclid's Elements, and The Nine Chapters on the Mathematical Art. The geometric work of the Greeks, typified in the Elements, provided the framework for generalizing formulae beyond the solution of particular problems into more general systems of stating and solving equations.
Later, the Indian mathematicians developed algebraic methods to a high degree of sophistication. Although Diophantus and the Babylonians used mostly special ad hoc methods to solve equations, Brahmagupta was the first to solve equations using general methods. He solved the linear indeterminate equations, quadratic equations, second order indeterminate equations and equations with multiple variable.
The word "algebra" is named after the Arabic word "al-jabr" from the title of the book Template:Unicode, meaning The book of Summary Concerning Calculating by Transposition and Reduction, a book written by the Persian mathematician Template:Unicode in 820. The word Al-Jabr means "reunion". The Hellenistic mathematician Diophantus has traditionally been known as "the father of algebra" but debate now exists as to whether or not Al-Khwarizmi should take that title.[3] Those who support Al-Khwarizmi point to the fact that much of his work on reduction is still in use today and that he gave an exhaustive explanation of solving quadratic equations. Those who support Diophantus point to the fact that the algebra found in Al-Jabr is more elementary than the algebra found in Arithmetica and that Arithmetica is syncopated while Al-Jabr is fully rhetorical.[4] Another Persian mathematician, Omar Khayyam, developed algebraic geometry and found the general geometric solution of the cubic equation. The Indian mathematicians Mahavira and Bhaskara II, and the Chinese mathematician Zhu Shijie, solved various cases of cubic, quartic, quintic and higher-order polynomial equations.
Another key event in the further development of algebra was the general algebraic solution of the cubic and quartic equations, developed in the mid-16th century. The idea of a determinant was developed by Japanese mathematician Kowa Seki in the 17th century, followed by Gottfried Leibniz ten years later, for the purpose of solving systems of simultaneous linear equations using matrices. Gabriel Cramer also did some work on matrices and determinants in the 18th century. Abstract algebra was developed in the 19th century, initially focusing on what is now called Galois theory, and on constructibility issues.
The stages of the development of symbolic algebra are roughly as follows:
- Rhetorical algebra, which was developed by the Babylonians and remained dominant up to the 16th century;
- Geometric constructive algebra, which was emphasised by the Vedic Indian and classical Greek mathematicians;
- Syncopated algebra, as developed by Diophantus, Brahmagupta and the Bakhshali Manuscript; and
- Symbolic algebra, which was initiated by Abū al-Hasan ibn Alī al-Qalasādī[5] and sees its culmination in the work of Gottfried Leibniz.
A timeline of key algebraic developments are as follows:
- Circa 1800 BC: The Old Babylonian Strassburg tablet seeks the solution of a quadratic elliptic equation.
- Circa 1600 BC: The Plimpton 322 tablet gives a table of Pythagorean triples in Babylonian Cuneiform script.
- Circa 800 BC: Indian mathematician Baudhayana, in his Baudhayana Sulba Sutra, discovers Pythagorean triples algebraically, finds geometric solutions of linear equations and quadratic equations of the forms ax2 = c and ax2 + bx = c, and finds two sets of positive integral solutions to a set of simultaneous Diophantine equations.
- Circa 600 BC: Indian mathematician Apastamba, in his Apastamba Sulba Sutra, solves the general linear equation and uses simultaneous Diophantine equations with up to five unknowns.
- Circa 300 BC: In Book II of his Elements, Euclid gives a geometric construction with Euclidean tools for the solution of the quadratic equation for positive real roots. The construction is due to the Pythagorean School of geometry.
- Circa 300 BC: A geometric construction for the solution of the cubic is sought (doubling the cube problem). It is now well known that the general cubic has no such solution using Euclidean tools.
- Circa 100 BC: Algebraic equations are treated in the Chinese mathematics book Jiuzhang suanshu (The Nine Chapters on the Mathematical Art), which contains solutions of linear equations solved using the rule of double false position, geometric solutions of quadratic equations, and the solutions of matrices equivalent to the modern method, to solve systems of simultaneous linear equations.
- Circa 100 BC: The Bakhshali Manuscript written in ancient India uses a form of algebraic notation using letters of the alphabet and other signs, and contains cubic and quartic equations, algebraic solutions of linear equations with up to five unknowns, the general algebraic formula for the quadratic equation, and solutions of indeterminate quadratic equations and simultaneous equations.
- Circa 150 AD: Hero of Alexandria treats algebraic equations in three volumes of mathematics.
- Circa 200: Diophantus, who lived in Egypt and is often considered the "father of algebra", writes his famous Arithmetica, a work featuring solutions of algebraic equations and on the theory of numbers.
- 499: Indian mathematician Aryabhata, in his treatise Aryabhatiya, obtains whole-number solutions to linear equations by a method equivalent to the modern one, describes the general integral solution of the indeterminate linear equation and gives integral solutions of simultaneous indeterminate linear equations.
- Circa 625: Chinese mathematician Wang Xiaotong finds numerical solutions of cubic equations.
- 628: Indian mathematician Brahmagupta, in his treatise Brahma Sputa Siddhanta, invents the chakravala method of solving indeterminate quadratic equations, including Pell's equation, and gives rules for solving linear and quadratic equations.
- 820: The word algebra is derived from operations described in the treatise written by the Persian mathematician Template:Unicode titled Al-Kitab al-Jabr wa-l-Muqabala (meaning "The Compendious Book on Calculation by Completion and Balancing") on the systematic solution of linear and quadratic equations. Al-Khwarizmi is often considered as the "father of algebra", much of whose works on reduction was included in the book and added to many methods we have in algebra now.
- Circa 850: Persian mathematician al-Mahani conceived the idea of reducing geometrical problems such as duplicating the cube to problems in algebra.
- Circa 850: Indian mathematician Mahavira solves various quadratic, cubic, quartic, quintic and higher-order equations, as well as indeterminate quadratic, cubic and higher-order equations.
- Circa 990: Persian Abu Bakr al-Karaji, in his treatise al-Fakhri, further develops algebra by extending Al-Khwarizmi's methodology to incorporate integral powers and integral roots of unknown quantities. He replaces geometrical operations of algebra with modern arithmetical operations, and defines the monomials x, x2, x3, ... and 1/x, 1/x2, 1/x3, ... and gives rules for the products of any two of these.
- Circa 1050: Chinese mathematician Jia Xian finds numerical solutions of polynomial equations.
- 1072: Persian mathematician Omar Khayyam develops algebraic geometry and, in the Treatise on Demonstration of Problems of Algebra, gives a complete classification of cubic equations with general geometric solutions found by means of intersecting conic sections.
- 1114: Indian mathematician Bhaskara, in his Bijaganita (Algebra), recognizes that a positive number has both a positive and negative square root, and solves various cubic, quartic and higher-order polynomial equations, as well as the general quadratic indeterminant equation.
- 1202: Algebra is introduced to Europe largely through the work of Leonardo Fibonacci of Pisa in his work Liber Abaci.
- Circa 1300: Chinese mathematician Zhu Shijie deals with polynomial algebra, solves quadratic equations, simultaneous equations and equations with up to four unknowns, and numerically solves some quartic, quintic and higher-order polynomial equations.
- Circa 1400: Indian mathematician Madhava of Sangamagramma finds iterative methods for approximate solution of non-linear equations.
- Circa 1450: Arab mathematician Abū al-Hasan ibn Alī al-Qalasādī took "the first steps toward the introduction of algebraic symbolism." He represented mathematical symbols using characters from the Arabic alphabet.[5]
- 1535: Nicolo Fontana Tartaglia and others mathematicians in Italy independently solved the general cubic equation.[6]
- 1545: Girolamo Cardano publishes Ars magna -The great art which gives Fontana's solution to the general quartic equation.[6]
- 1572: Rafael Bombelli recognizes the complex roots of the cubic and improves current notation.
- 1591: Francois Viete develops improved symbolic notation for various powers of an unknown and uses vowels for unknowns and consonants for constants in In artem analyticam isagoge.
- 1631: Thomas Harriot in a posthumous publication uses exponential notation and is the first to use symbols to indicate "less than" and "greater than".
- 1682: Gottfried Wilhelm Leibniz develops his notion of symbolic manipulation with formal rules which he calls characteristica generalis.
- 1680s: Japanese mathematician Kowa Seki, in his Method of solving the dissimulated problems, discovers the determinant, and Bernoulli numbers.[7]
- 1750: Gabriel Cramer, in his treatise Introduction to the analysis of algebraic curves, states Cramer's rule and studies algebraic curves, matrices and determinants.
- 1824: Niels Henrik Abel proved that the general quintic equation is insoluble by radicals.[6]
- 1832: Galois theory is developed by Évariste Galois in his work on abstract algebra.[6] | https://www.wikidoc.org/index.php/Algebra | |
6bc7836136900ecd180250a29039a4fbe2943f7f | wikidoc | Alitame | Alitame
Alitame is an artificial sweetener developed by Pfizer in the early 1980s and currently marketed in some countries under the brand name Aclame. Like aspartame, alitame is an aspartic acid-containing dipeptide. Most dipeptides are not sweet, but the unexpected discovery of aspartame in 1965 led to a search for similar compounds that shared its sweetness. Alitame is one such second-generation dipeptide sweetener. Neotame, developed by the owners of the NutraSweet brand, is another.
Alitame has several distinct advantages over aspartame. It is about 2000 times sweeter than sucrose, about 10 times sweeter than aspartame, and has no aftertaste. Its half-life under hot or acidic conditions is about twice as long as aspartame's, although some other artificial sweeteners, including saccharin and acesulfame potassium, are more stable yet. Unlike aspartame, alitame does not contain phenylalanine, and can therefore be used by people with phenylketonuria.
Alitame has approved for use in Mexico, Australia, New Zealand and China. Danisco Cultor America Inc.'s Food and Drug Administration petition to permit alitame's use in the United States is currently in abeyance. | Alitame
Template:Chembox new
Alitame is an artificial sweetener developed by Pfizer in the early 1980s and currently marketed in some countries under the brand name Aclame.[1] Like aspartame, alitame is an aspartic acid-containing dipeptide. Most dipeptides are not sweet, but the unexpected discovery of aspartame in 1965 led to a search for similar compounds that shared its sweetness. Alitame is one such second-generation dipeptide sweetener. Neotame, developed by the owners of the NutraSweet brand, is another.
Alitame has several distinct advantages over aspartame. It is about 2000 times sweeter than sucrose, about 10 times sweeter than aspartame, and has no aftertaste. Its half-life under hot or acidic conditions is about twice as long as aspartame's, although some other artificial sweeteners, including saccharin and acesulfame potassium, are more stable yet. Unlike aspartame, alitame does not contain phenylalanine, and can therefore be used by people with phenylketonuria.
Alitame has approved for use in Mexico, Australia, New Zealand and China. Danisco Cultor America Inc.'s Food and Drug Administration petition to permit alitame's use in the United States is currently in abeyance.[2] | https://www.wikidoc.org/index.php/Alitame | |
85d3252ac14b125e5f2207e9174b8c3b6ac0196b | wikidoc | Benzene | Benzene
# Overview
Benzene, or Benzol (see also Benzine) is an organic chemical compound with the formula C6H6. It is sometimes abbreviated Ph–H. Benzene is a colorless and flammable liquid with a sweet smell and a relatively high melting point. It is carcinogenic and its use as an additive in gasoline is now limited, but it is an important industrial solvent and precursor in the production of drugs, plastics, synthetic rubber, and dyes. Benzene is a natural constituent of crude oil, but it is usually synthesized from other compounds present in petroleum. Benzene is an aromatic hydrocarbon and the second -annulene (-annulene), a cyclic hydrocarbon with a continuous pi bond.
# History
The word benzene derives historically from "gum benzoin", sometimes called "benjamin" (i.e., benzoin resin), an aromatic resin known to European pharmacists and perfumers since the fifteenth century as a product of southeast Asia. "Benzoin" is itself a corruption of the Arabic expression "luban jawi," or "frankincense of Java." An acidic material was derived from benzoin by sublimation, and named "flowers of benzoin," or benzoic acid. The hydrocarbon derived from benzoic acid thus acquired the name benzin, benzol, or benzene.
Benzene has been the subject of many studies by scientists ranging from Michael Faraday to Linus Pauling. Faraday first isolated benzene in 1825 from the oily residue derived from the production of illuminating gas, giving it the name bicarburet of hydrogen.
In 1833, Eilhard Mitscherlich produced it via the distillation of benzoic acid (from gum benzoin) and lime. Mitscherlich gave the compound the name benzin. In 1836 the French chemist Auguste Laurent named the substance "phène"; this is the root of the word phenol, which is hydroxylated benzene, and phenyl, which is the radical formed by abstraction of a hydrogen atom from benzene.
In 1845, Charles Mansfield, working under August Wilhelm von Hofmann, isolated benzene from coal tar. Four years later, Mansfield began the first industrial-scale production of benzene, based on the coal-tar method.
Gradually the sense developed among chemists that substances related to benzene formed a natural chemical family. In 1855 August Wilhelm Hofmann used the word "aromatic" to designate this family relationship, after a characteristic property of many of its members.
The empirical formula for benzene was long known, but its highly polyunsaturated structure was challenging to determine. Archibald Scott Couper in 1858 and Joseph Loschmidt in 1861 suggested possible structures that contained multiple double bonds or multiple rings, but the study of aromatic compounds was in its very early years, and too little evidence was then available to help chemists decide on any particular structure.
In 1865 the German chemist Friedrich August Kekulé published a paper in French (for he was then teaching in Francophone Belgium) suggesting that the structure contained a six-membered ring of carbon atoms with alternating single and double bonds. The next year he published a much longer paper in German on the same subject. Kekulé used evidence that had accumulated in the intervening years—namely, that there always appeared to be only one isomer of any monoderivative of benzene, and that there always appeared to be exactly three isomers of every diderivative—to argue in support of his proposed structure. Kekulé's symmetrical ring could explain these curious facts.
The new understanding of benzene, and hence of all aromatic compounds, proved to be so important for both pure and applied chemistry that in 1890 the German Chemical Society organized an elaborate appreciation in Kekulé's honor, celebrating the twenty-fifth anniversary of his first benzene paper. Here Kekulé spoke of the creation of the theory. He said that he had discovered the ring shape of the benzene molecule after having a reverie or day-dream of a snake seizing its own tail (this is a common symbol in many ancient cultures known as the Ouroboros). This vision, he said, came to him after years of studying the nature of carbon-carbon bonds. This was 20 years after he had solved the problem of how carbon atoms could bond to up to four other atoms at the same time. It is curious that a similar humorous depiction of benzene had appeared in 1886 in the Berichte der Durstigen Chemischen Gesellschaft (Journal of the Thirsty Chemical Society), a parody of the Berichte der Deutschen Chemischen Gesellschaft, only the parody had monkeys seizing each other in a circle, rather than snakes as in Kekulé's anecdote. Some historians have suggested that the parody was a lampoon of the snake anecdote, possibly already well-known through oral transmission even if it had not yet appeared in print. Others have speculated that Kekulé's story in 1890 was a re-parody of the monkey spoof, and was a mere invention rather than a recollection of an event in his life.
Kekulé's 1890 speech in which these anecdotes appeared has been translated into English. If one takes the anecdote as the memory of a real event, circumstances mentioned in the story suggest that it must have happened early in 1862.
The cyclic nature of benzene was finally confirmed by the eminent crystallographer Kathleen Lonsdale.
# Structure
Benzene represents a special problem in that, to account for all the bonds, there must be alternating double carbon bonds:
Using X-ray diffraction, researchers discovered that all of the carbon-carbon bonds in benzene are of the same length of 140 picometres (pm). The C–C bond lengths are greater than a double bond (135pm) but shorter than a single bond (147pm). This intermediate distance is explained by electron delocalization: the electrons for C–C bonding are distributed equally between each of the six carbon atoms. One representation is that the structure exists as a superposition of so-called resonance structures, rather than either form individually. This delocalisation of electrons is known as aromaticity, and gives benzene great stability. This enhanced stability is the fundamental property of aromatic molecules that differentiates them from molecules that are non-aromatic. To reflect the delocalised nature of the bonding, benzene is often depicted with a circle inside a hexagonal arrangement of carbon atoms:
As is common in organic chemistry, the carbon atoms in the diagram above have been left unlabeled. Benzene occurs sufficiently often as a component of organic molecules that there is a Unicode symbol with the code 232C to represent it:
Many fonts do not have this Unicode character, so many programs may not be able to display it correctly. A graphical representation of this symbol can be found at the following URL:
# Substituted benzene derivatives
Many important chemicals are derived from benzene, wherein with one or more of the hydrogen atoms is replaced with another functional group. Examples of simple benzene derivatives are phenol, toluene, and aniline, abbreviated PhOH, PhMe, and PhNH2, respectively. Linking benzene rings gives biphenyl, C6H5–C6H5. Further loss of hydrogen gives "fused" aromatic hydrocarbons, such as naphthalene and anthracene. The limit of the fusion process is the hydrogen-free material graphite.
In heterocycles, carbon atoms in the benzene ring are replaced with other elements. The most important derivatives are the rings containing nitrogen. Replacing one CH with N gives the compound pyridine, C5H5N. Although benzene and pyridine are structurally related, benzene cannot be converted into pyridine. Replacement of a second CH bond with N gives, depending on the location of the second N, pyridazine, pyrimidine, and pyrazine.
# Production
Trace amounts of benzene may result whenever carbon-rich materials undergo incomplete combustion. It is produced in volcanoes and forest fires, and is also a component of cigarette smoke.
Up until World War II, most benzene was produced as a byproduct of coke production (or "coke-oven light oil") in the steel industry. However, in the 1950s, increased demand for benzene, especially from the growing plastics industry, necessitated the production of benzene from petroleum. Today, most benzene comes from the petrochemical industry, with only a small fraction being produced from coal.
Three chemical processes contribute equally to industrial benzene production: catalytic reforming, toluene hydrodealkylation, and steam cracking.
## Catalytic reforming
In catalytic reforming, a mixture of hydrocarbons with boiling points between 60–200 °C is blended with hydrogen gas and then exposed to a bifunctional platinum chloride or rhenium chloride catalyst at 500–525 °C and pressures ranging from 8–50 atm. Under these conditions, aliphatic hydrocarbons form rings and lose hydrogen to become aromatic hydrocarbons. The aromatic products of the reaction are then separated from the reaction mixture (or reformate) by extraction with any one of a number of solvents, including diethylene glycol or sulfolane, and benzene is then separated from the other aromatics by distillation. The extraction step of aromatics from the reformate is designed to produce aromatics with lowest non-aromatic components. So-called "BTX (Benzene-Toluene-Xylenes)" process consists of such extraction and distillation steps.
Similarly to this catalytic reforming, UOP and BP commercialized a method from LPG (mainly propane and butane) to aromatics.
## Toluene hydrodealkylation
Toluene hydrodealkylation converts toluene to benzene. In this hydrogen-intensive process, toluene is mixed with hydrogen, then passed over a chromium, molybdenum, or platinum oxide catalyst at 500–600 °C and 40–60 atm pressure. Sometimes, higher temperatures are used instead of a catalyst (at the similar reaction condition). Under these conditions, toluene undergoes dealkylation according to the chemical equation:
This irreversible reaction is accompanied by an equilibrium side reaction that produces
biphenyl (aka diphenyl) at higher temperature:
2 C6H6 ↔ H2 + C12H10
If the raw material stream contains much non-aromatic components (paraffins or naphthenes), those are likely decomposed to lower hydrocarbons such as methane, which increases the consumption of hydrogen.
A typical reaction yield exceeds 95%. Sometimes, xylenes and heavier aromatics are used in place of toluene, with similar efficiency.
This is often called "on-purpose" methodology to produce benzene, compared to conventional BTX (benzene-toluene-xylene) processes. The hydrodealkylation process is not economically feasible if the price gap between benzene and toluene is small (or the gap is smaller than about 15% of benzene price).
## Toluene disproportionation
Where a chemical complex has similar demands for both benzene and xylene, then toluene disproportionation (TDP) may be an attractive alternative to the toluene hydrodealkylation. Broadly speaking 2 toluene molecules are reacted and the methyl groups rearranged from one toluene molecule to the other, yielding one benzene molecule and one xylene molecule.
Given that demand for para-xylene (p-xylene) substantially exceeds demand for other xylene isomers, a refinement of the TDP process called Selective TDP (STDP) may be used. In this process, the xylene stream exiting the TDP unit is approximately 90% paraxylene. In some current catalytic systems, even the benzene-to-xylenes ratio is decreased (more xylenes) when the demand of xylenes is higher.
## Steam cracking
Steam cracking is the process for producing ethylene and other olefins from aliphatic hydrocarbons. Depending on the feedstock used to produce the olefins, steam cracking can produce a benzene-rich liquid byproduct called pyrolysis gasoline. Pyrolysis gasoline can be blended with other hydrocarbons as a gasoline additive, or distilled (in BTX process) to separate it into its components, including benzene.
# Uses
## Early uses
In the 19th and early-20th centuries, benzene was used as an after-shave lotion because of its pleasant smell. Prior to the 1920s, benzene was frequently used as an industrial solvent, especially for degreasing metal. As its toxicity became obvious, benzene was supplanted by other solvents, especially toluene (methyl benzene), which has similar physical properties but is not as carcinogenic.
In 1903, Ludwig Roselius popularized the use of benzene to decaffeinate coffee. This discovery led to the production of Sanka (the letters "ka" in the brand name stand for kaffein). This process was later discontinued.
As a petrol additive, benzene increases the octane rating and reduces knocking. Consequently, petrol often contained several percent benzene before the 1950s, when tetraethyl lead replaced it as the most widely-used antiknock additive. With the global phaseout of leaded petrol, benzene has made a comeback as a gasoline additive in some nations. In the United States, concern over its negative health effects and the possibility of benzene entering the groundwater have led to stringent regulation of petrol's benzene content, with limits typically around 1%. European petrol specifications now contain the same 1% limit on benzene content. The US EPA has new regulations that will lower the benzene content in gasoline to 0.62% in 2011..
## Current uses of benzene
Today benzene is mainly used as an intermediate to make other chemicals. Its most widely-produced derivatives include styrene, which is used to make polymers and plastics, phenol for resins and adhesives (via cumene), and cyclohexane, which is used in the manufacture of Nylon. Smaller amounts of benzene are used to make some types of rubbers, lubricants, dyes, detergents, drugs, explosives, napalm and pesticides.
In laboratory research, toluene is now often used as a substitute for benzene. The solvent-properties of the two are similar but toluene is less toxic and has a wider liquid range.
Benzene has been used as a basic research tool in a variety of experiments including analysis of a two-dimensional gas.
Used in watchmaking for the cleaning of hairsprings.
# Reactions of benzene
- Electrophilic aromatic substitution is a general method of derivatizing benzene. Benzene is sufficiently nucleophilic that it undergoes substitution by acylium ions or alkyl carbocations to give substituted derivatives.
- The Friedel-Crafts acylation is a specific example of electrophilic aromatic substitution. The reaction involves the acylation of benzene (or many other aromatic rings) with an acyl chloride using a strong Lewis acid catalyst such as aluminium chloride or iron chloride which act as a halogen carrier.
- The Friedel-Crafts acylation is a specific example of electrophilic aromatic substitution. The reaction involves the acylation of benzene (or many other aromatic rings) with an acyl chloride using a strong Lewis acid catalyst such as aluminium chloride or iron chloride which act as a halogen carrier.
- Like the Friedel-Crafts acylation, the Friedel-Crafts alkylation involves the alkylation of benzene (and many other aromatic rings) using an alkyl halide in the presence of a strong Lewis acid catalyst.
sulfonation.
Nitration: Benzene undergoes nitration with nitronioum ions (NO2+) as the electrophile. Thus, warming benzene at 50-55 degrees Celsius, with a combination of concentrated sulphuric and nitric acid to produce the electrophile, gives nitrobenzene.
- Like the Friedel-Crafts acylation, the Friedel-Crafts alkylation involves the alkylation of benzene (and many other aromatic rings) using an alkyl halide in the presence of a strong Lewis acid catalyst.
- sulfonation.
- Nitration: Benzene undergoes nitration with nitronioum ions (NO2+) as the electrophile. Thus, warming benzene at 50-55 degrees Celsius, with a combination of concentrated sulphuric and nitric acid to produce the electrophile, gives nitrobenzene.
- Hydrogenation(Reduction): Benzene and derivatives convert to cyclohexane and derivatives when treated with hydrogen at 450K and 10atm of pressure with a finely divided nickel catalyst.
- Benzene is an excellent ligand in the organometallic chemistry of low-valent metals. Important examples include the sandwich and half-sandwich complexes respectively Cr(C6H6)2 and 2.
# Health effects
Benzene exposure has serious health effects. Breathing high levels of benzene can result in death, while low levels can cause drowsiness, dizziness, rapid heart rate, headaches, tremors, confusion, and unconsciousness. Eating or drinking foods containing high levels of benzene can cause vomiting, irritation of the stomach, dizziness, sleepiness, convulsions, rapid heart rate, and death.
The major effects of benzene are chronic (long-term) exposure through the blood. Benzene damages the bone marrow and can cause a decrease in red blood cells, leading to anemia. It can also cause excessive bleeding and depress the immune system, increasing the chance of infection.
Some women who breathed high levels of benzene for many months had irregular menstrual periods and a decrease in the size of their ovaries. It is not known whether benzene exposure affects the developing fetus in pregnant women or fertility in men.
Animal studies have shown low birth weights, delayed bone formation, and bone marrow damage when pregnant animals breathed benzene.
The US Department of Health and Human Services (DHHS) classifies benzene as a human carcinogen. Long-term exposure to high levels of benzene in the air can cause leukemia, a potentially fatal cancer of the blood-forming organs. In particular, Acute myeloid leukemia or acute non-lymphocytic leukaemia (AML & ANLL) may be caused by benzene.
Several tests can determine exposure to benzene. There is a test for measuring benzene in the breath; this test must be done shortly after exposure. Benzene can also be measured in the blood; however, because benzene disappears rapidly from the blood, measurements are accurate only for recent exposures.
In the body, benzene is metabolized. Certain metabolites can be measured in the urine. However, this test must be done shortly after exposure and is not a reliable indicator of benzene exposure, since the same metabolites may be present in urine from other sources.
The United States Environmental Protection Agency has set the maximum permissible level of benzene in drinking water at 0.005 milligrams per liter (0.005 mg/L). The EPA requires that spills or accidental releases into the environment of 10 pounds (4.5 kg) or more of benzene be reported to the EPA.
The US Occupational Safety and Health Administration (OSHA) has set a permissible exposure limit of 0.5 part of benzene per million parts of air (.5 ppm) in the workplace during an 8-hour workday, 40-hour workweek. The short term exposure limit for airborne benzene is 5 ppm for 15 minutes.
In recent history there have been many examples of the harmful health effects of benzene and its derivatives. Toxic Oil Syndrome caused localised immune-suppression in Madrid in 1981 from people ingesting anilide-contaminated rapeseed oil. Chronic Fatigue Syndrome has also been highly correlated with people who eat "denatured" food that use solvents to remove fat or contain benzoic acid.
Workers in various industries that make or use benzene may be at risk for being exposed to high levels of this carcinogenic chemical. Industries that involve the use of benzene include the rubber industry, oil refineries, chemical plants, shoe manufacturers, and gasoline related industries. In 1987, OSHA estimated that about 237,000 workers in the United States were potentially exposed to benzene, and it is not known if this number has substantially changed since then.
Water and soil contamination are important pathways of concern for transmission of benzene contact. In the U.S. alone there are approximately 100,000 different sites which have benzene soil or groundwater contamination. In 2005, the water supply to the city of Harbin in China with a population of almost nine million people, was cut off because of a major benzene exposure. Benzene leaked into the Songhua River, which supplies drinking water to the city, after an explosion at a China National Petroleum Corporation (CNPC) factory in the city of Jilin on 13 November.
In March 2006, the official Food Standards Agency in Britain conducted a survey of 150 brands of soft drinks. It found that four contained benzene levels above World Health Organization limits. The affected batches were removed from sale. See benzene in soft drinks | Benzene
Template:Chembox new
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Benzene, or Benzol (see also Benzine) is an organic chemical compound with the formula C6H6. It is sometimes abbreviated Ph–H. Benzene is a colorless and flammable liquid with a sweet smell and a relatively high melting point. It is carcinogenic and its use as an additive in gasoline is now limited, but it is an important industrial solvent and precursor in the production of drugs, plastics, synthetic rubber, and dyes. Benzene is a natural constituent of crude oil, but it is usually synthesized from other compounds present in petroleum. Benzene is an aromatic hydrocarbon and the second [n]-annulene ([6]-annulene), a cyclic hydrocarbon with a continuous pi bond.
# History
The word benzene derives historically from "gum benzoin", sometimes called "benjamin" (i.e., benzoin resin), an aromatic resin known to European pharmacists and perfumers since the fifteenth century as a product of southeast Asia. "Benzoin" is itself a corruption of the Arabic expression "luban jawi," or "frankincense of Java." An acidic material was derived from benzoin by sublimation, and named "flowers of benzoin," or benzoic acid. The hydrocarbon derived from benzoic acid thus acquired the name benzin, benzol, or benzene.[1]
Benzene has been the subject of many studies by scientists ranging from Michael Faraday to Linus Pauling. Faraday first isolated benzene in 1825 from the oily residue derived from the production of illuminating gas, giving it the name bicarburet of hydrogen.[2][3]
In 1833, Eilhard Mitscherlich produced it via the distillation of benzoic acid (from gum benzoin) and lime. Mitscherlich gave the compound the name benzin.[4] In 1836 the French chemist Auguste Laurent named the substance "phène"; this is the root of the word phenol, which is hydroxylated benzene, and phenyl, which is the radical formed by abstraction of a hydrogen atom from benzene.
In 1845, Charles Mansfield, working under August Wilhelm von Hofmann, isolated benzene from coal tar. Four years later, Mansfield began the first industrial-scale production of benzene, based on the coal-tar method.
Gradually the sense developed among chemists that substances related to benzene formed a natural chemical family. In 1855 August Wilhelm Hofmann used the word "aromatic" to designate this family relationship, after a characteristic property of many of its members.
The empirical formula for benzene was long known, but its highly polyunsaturated structure was challenging to determine. Archibald Scott Couper in 1858 and Joseph Loschmidt in 1861 suggested possible structures that contained multiple double bonds or multiple rings, but the study of aromatic compounds was in its very early years, and too little evidence was then available to help chemists decide on any particular structure.
In 1865 the German chemist Friedrich August Kekulé published a paper in French (for he was then teaching in Francophone Belgium) suggesting that the structure contained a six-membered ring of carbon atoms with alternating single and double bonds. The next year he published a much longer paper in German on the same subject.[5][6] Kekulé used evidence that had accumulated in the intervening years—namely, that there always appeared to be only one isomer of any monoderivative of benzene, and that there always appeared to be exactly three isomers of every diderivative—to argue in support of his proposed structure. Kekulé's symmetrical ring could explain these curious facts.
The new understanding of benzene, and hence of all aromatic compounds, proved to be so important for both pure and applied chemistry that in 1890 the German Chemical Society organized an elaborate appreciation in Kekulé's honor, celebrating the twenty-fifth anniversary of his first benzene paper. Here Kekulé spoke of the creation of the theory. He said that he had discovered the ring shape of the benzene molecule after having a reverie or day-dream of a snake seizing its own tail (this is a common symbol in many ancient cultures known as the Ouroboros). This vision, he said, came to him after years of studying the nature of carbon-carbon bonds. This was 20 years after he had solved the problem of how carbon atoms could bond to up to four other atoms at the same time. It is curious that a similar humorous depiction of benzene had appeared in 1886 in the Berichte der Durstigen Chemischen Gesellschaft (Journal of the Thirsty Chemical Society), a parody of the Berichte der Deutschen Chemischen Gesellschaft, only the parody had monkeys seizing each other in a circle, rather than snakes as in Kekulé's anecdote.[7] Some historians have suggested that the parody was a lampoon of the snake anecdote, possibly already well-known through oral transmission even if it had not yet appeared in print.[1] Others have speculated that Kekulé's story in 1890 was a re-parody of the monkey spoof, and was a mere invention rather than a recollection of an event in his life.
Kekulé's 1890 speech[8] in which these anecdotes appeared has been translated into English.[9] If one takes the anecdote as the memory of a real event, circumstances mentioned in the story suggest that it must have happened early in 1862.[10]
The cyclic nature of benzene was finally confirmed by the eminent crystallographer Kathleen Lonsdale.[11][12]
# Structure
Benzene represents a special problem in that, to account for all the bonds, there must be alternating double carbon bonds:
Using X-ray diffraction, researchers discovered that all of the carbon-carbon bonds in benzene are of the same length of 140 picometres (pm). The C–C bond lengths are greater than a double bond (135pm) but shorter than a single bond (147pm). This intermediate distance is explained by electron delocalization: the electrons for C–C bonding are distributed equally between each of the six carbon atoms. One representation is that the structure exists as a superposition of so-called resonance structures, rather than either form individually. This delocalisation of electrons is known as aromaticity, and gives benzene great stability. This enhanced stability is the fundamental property of aromatic molecules that differentiates them from molecules that are non-aromatic. To reflect the delocalised nature of the bonding, benzene is often depicted with a circle inside a hexagonal arrangement of carbon atoms:
As is common in organic chemistry, the carbon atoms in the diagram above have been left unlabeled. Benzene occurs sufficiently often as a component of organic molecules that there is a Unicode symbol with the code 232C to represent it:
Template:Unicode
Many fonts do not have this Unicode character, so many programs may not be able to display it correctly. A graphical representation of this symbol can be found at the following URL: http://www.fileformat.info/info/unicode/char/232c/index.htm
# Substituted benzene derivatives
Many important chemicals are derived from benzene, wherein with one or more of the hydrogen atoms is replaced with another functional group. Examples of simple benzene derivatives are phenol, toluene, and aniline, abbreviated PhOH, PhMe, and PhNH2, respectively. Linking benzene rings gives biphenyl, C6H5–C6H5. Further loss of hydrogen gives "fused" aromatic hydrocarbons, such as naphthalene and anthracene. The limit of the fusion process is the hydrogen-free material graphite.
In heterocycles, carbon atoms in the benzene ring are replaced with other elements. The most important derivatives are the rings containing nitrogen. Replacing one CH with N gives the compound pyridine, C5H5N. Although benzene and pyridine are structurally related, benzene cannot be converted into pyridine. Replacement of a second CH bond with N gives, depending on the location of the second N, pyridazine, pyrimidine, and pyrazine.
# Production
Trace amounts of benzene may result whenever carbon-rich materials undergo incomplete combustion. It is produced in volcanoes and forest fires, and is also a component of cigarette smoke.
Up until World War II, most benzene was produced as a byproduct of coke production (or "coke-oven light oil") in the steel industry. However, in the 1950s, increased demand for benzene, especially from the growing plastics industry, necessitated the production of benzene from petroleum. Today, most benzene comes from the petrochemical industry, with only a small fraction being produced from coal.
Three chemical processes contribute equally to industrial benzene production: catalytic reforming, toluene hydrodealkylation, and steam cracking.
## Catalytic reforming
In catalytic reforming, a mixture of hydrocarbons with boiling points between 60–200 °C is blended with hydrogen gas and then exposed to a bifunctional platinum chloride or rhenium chloride catalyst at 500–525 °C and pressures ranging from 8–50 atm. Under these conditions, aliphatic hydrocarbons form rings and lose hydrogen to become aromatic hydrocarbons. The aromatic products of the reaction are then separated from the reaction mixture (or reformate) by extraction with any one of a number of solvents, including diethylene glycol or sulfolane, and benzene is then separated from the other aromatics by distillation. The extraction step of aromatics from the reformate is designed to produce aromatics with lowest non-aromatic components. So-called "BTX (Benzene-Toluene-Xylenes)" process consists of such extraction and distillation steps.
Similarly to this catalytic reforming, UOP and BP commercialized a method from LPG (mainly propane and butane) to aromatics.
## Toluene hydrodealkylation
Toluene hydrodealkylation converts toluene to benzene. In this hydrogen-intensive process, toluene is mixed with hydrogen, then passed over a chromium, molybdenum, or platinum oxide catalyst at 500–600 °C and 40–60 atm pressure. Sometimes, higher temperatures are used instead of a catalyst (at the similar reaction condition). Under these conditions, toluene undergoes dealkylation according to the chemical equation:
This irreversible reaction is accompanied by an equilibrium side reaction that produces
biphenyl (aka diphenyl) at higher temperature:
2 C6H6 ↔ H2 + C12H10
If the raw material stream contains much non-aromatic components (paraffins or naphthenes), those are likely decomposed to lower hydrocarbons such as methane, which increases the consumption of hydrogen.
A typical reaction yield exceeds 95%. Sometimes, xylenes and heavier aromatics are used in place of toluene, with similar efficiency.
This is often called "on-purpose" methodology to produce benzene, compared to conventional BTX (benzene-toluene-xylene) processes. The hydrodealkylation process is not economically feasible if the price gap between benzene and toluene is small (or the gap is smaller than about 15% of benzene price).
## Toluene disproportionation
Where a chemical complex has similar demands for both benzene and xylene, then toluene disproportionation (TDP) may be an attractive alternative to the toluene hydrodealkylation. Broadly speaking 2 toluene molecules are reacted and the methyl groups rearranged from one toluene molecule to the other, yielding one benzene molecule and one xylene molecule.
Given that demand for para-xylene (p-xylene) substantially exceeds demand for other xylene isomers, a refinement of the TDP process called Selective TDP (STDP) may be used. In this process, the xylene stream exiting the TDP unit is approximately 90% paraxylene. In some current catalytic systems, even the benzene-to-xylenes ratio is decreased (more xylenes) when the demand of xylenes is higher.
## Steam cracking
Steam cracking is the process for producing ethylene and other olefins from aliphatic hydrocarbons. Depending on the feedstock used to produce the olefins, steam cracking can produce a benzene-rich liquid byproduct called pyrolysis gasoline. Pyrolysis gasoline can be blended with other hydrocarbons as a gasoline additive, or distilled (in BTX process) to separate it into its components, including benzene.
# Uses
## Early uses
In the 19th and early-20th centuries, benzene was used as an after-shave lotion because of its pleasant smell. Prior to the 1920s, benzene was frequently used as an industrial solvent, especially for degreasing metal. As its toxicity became obvious, benzene was supplanted by other solvents, especially toluene (methyl benzene), which has similar physical properties but is not as carcinogenic.
In 1903, Ludwig Roselius popularized the use of benzene to decaffeinate coffee. This discovery led to the production of Sanka (the letters "ka" in the brand name stand for kaffein). This process was later discontinued.
As a petrol additive, benzene increases the octane rating and reduces knocking. Consequently, petrol often contained several percent benzene before the 1950s, when tetraethyl lead replaced it as the most widely-used antiknock additive. With the global phaseout of leaded petrol, benzene has made a comeback as a gasoline additive in some nations. In the United States, concern over its negative health effects and the possibility of benzene entering the groundwater have led to stringent regulation of petrol's benzene content, with limits typically around 1%. European petrol specifications now contain the same 1% limit on benzene content. The US EPA has new regulations that will lower the benzene content in gasoline to 0.62% in 2011.[13].
## Current uses of benzene
Today benzene is mainly used as an intermediate to make other chemicals. Its most widely-produced derivatives include styrene, which is used to make polymers and plastics, phenol for resins and adhesives (via cumene), and cyclohexane, which is used in the manufacture of Nylon. Smaller amounts of benzene are used to make some types of rubbers, lubricants, dyes, detergents, drugs, explosives, napalm and pesticides.
In laboratory research, toluene is now often used as a substitute for benzene. The solvent-properties of the two are similar but toluene is less toxic and has a wider liquid range.
Benzene has been used as a basic research tool in a variety of experiments including analysis of a two-dimensional gas.
Used in watchmaking for the cleaning of hairsprings.
# Reactions of benzene
- Electrophilic aromatic substitution is a general method of derivatizing benzene. Benzene is sufficiently nucleophilic that it undergoes substitution by acylium ions or alkyl carbocations to give substituted derivatives.
- The Friedel-Crafts acylation is a specific example of electrophilic aromatic substitution. The reaction involves the acylation of benzene (or many other aromatic rings) with an acyl chloride using a strong Lewis acid catalyst such as aluminium chloride or iron chloride which act as a halogen carrier.
- The Friedel-Crafts acylation is a specific example of electrophilic aromatic substitution. The reaction involves the acylation of benzene (or many other aromatic rings) with an acyl chloride using a strong Lewis acid catalyst such as aluminium chloride or iron chloride which act as a halogen carrier.
- Like the Friedel-Crafts acylation, the Friedel-Crafts alkylation involves the alkylation of benzene (and many other aromatic rings) using an alkyl halide in the presence of a strong Lewis acid catalyst.
sulfonation.
Nitration: Benzene undergoes nitration with nitronioum ions (NO2+) as the electrophile. Thus, warming benzene at 50-55 degrees Celsius, with a combination of concentrated sulphuric and nitric acid to produce the electrophile, gives nitrobenzene.
- Like the Friedel-Crafts acylation, the Friedel-Crafts alkylation involves the alkylation of benzene (and many other aromatic rings) using an alkyl halide in the presence of a strong Lewis acid catalyst.
- sulfonation.
- Nitration: Benzene undergoes nitration with nitronioum ions (NO2+) as the electrophile. Thus, warming benzene at 50-55 degrees Celsius, with a combination of concentrated sulphuric and nitric acid to produce the electrophile, gives nitrobenzene.
- Hydrogenation(Reduction): Benzene and derivatives convert to cyclohexane and derivatives when treated with hydrogen at 450K and 10atm of pressure with a finely divided nickel catalyst.
- Benzene is an excellent ligand in the organometallic chemistry of low-valent metals. Important examples include the sandwich and half-sandwich complexes respectively Cr(C6H6)2 and [RuCl2(C6H6)]2.
# Health effects
Benzene exposure has serious health effects. Breathing high levels of benzene can result in death, while low levels can cause drowsiness, dizziness, rapid heart rate, headaches, tremors, confusion, and unconsciousness. Eating or drinking foods containing high levels of benzene can cause vomiting, irritation of the stomach, dizziness, sleepiness, convulsions, rapid heart rate, and death.
The major effects of benzene are chronic (long-term) exposure through the blood. Benzene damages the bone marrow and can cause a decrease in red blood cells, leading to anemia. It can also cause excessive bleeding and depress the immune system, increasing the chance of infection.
Some women who breathed high levels of benzene for many months had irregular menstrual periods and a decrease in the size of their ovaries. It is not known whether benzene exposure affects the developing fetus in pregnant women or fertility in men.
Animal studies have shown low birth weights, delayed bone formation, and bone marrow damage when pregnant animals breathed benzene.
The US Department of Health and Human Services (DHHS) classifies benzene as a human carcinogen. Long-term exposure to high levels of benzene in the air can cause leukemia, a potentially fatal cancer of the blood-forming organs. In particular, Acute myeloid leukemia or acute non-lymphocytic leukaemia (AML & ANLL) may be caused by benzene.
Several tests can determine exposure to benzene. There is a test for measuring benzene in the breath; this test must be done shortly after exposure. Benzene can also be measured in the blood; however, because benzene disappears rapidly from the blood, measurements are accurate only for recent exposures.
In the body, benzene is metabolized. Certain metabolites can be measured in the urine. However, this test must be done shortly after exposure and is not a reliable indicator of benzene exposure, since the same metabolites may be present in urine from other sources.
The United States Environmental Protection Agency has set the maximum permissible level of benzene in drinking water at 0.005 milligrams per liter (0.005 mg/L). The EPA requires that spills or accidental releases into the environment of 10 pounds (4.5 kg) or more of benzene be reported to the EPA.
The US Occupational Safety and Health Administration (OSHA) has set a permissible exposure limit of 0.5 part of benzene per million parts of air (.5 ppm) in the workplace during an 8-hour workday, 40-hour workweek. The short term exposure limit for airborne benzene is 5 ppm for 15 minutes.
In recent history there have been many examples of the harmful health effects of benzene and its derivatives. Toxic Oil Syndrome caused localised immune-suppression in Madrid in 1981 from people ingesting anilide-contaminated rapeseed oil. Chronic Fatigue Syndrome has also been highly correlated with people who eat "denatured" food that use solvents to remove fat or contain benzoic acid.
Workers in various industries that make or use benzene may be at risk for being exposed to high levels of this carcinogenic chemical. Industries that involve the use of benzene include the rubber industry, oil refineries, chemical plants, shoe manufacturers, and gasoline related industries. In 1987, OSHA estimated that about 237,000 workers in the United States were potentially exposed to benzene, and it is not known if this number has substantially changed since then.
Water and soil contamination are important pathways of concern for transmission of benzene contact. In the U.S. alone there are approximately 100,000 different sites which have benzene soil or groundwater contamination. In 2005, the water supply to the city of Harbin in China with a population of almost nine million people, was cut off because of a major benzene exposure. Benzene leaked into the Songhua River, which supplies drinking water to the city, after an explosion at a China National Petroleum Corporation (CNPC) factory in the city of Jilin on 13 November.
In March 2006, the official Food Standards Agency in Britain conducted a survey of 150 brands of soft drinks. It found that four contained benzene levels above World Health Organization limits. The affected batches were removed from sale. See benzene in soft drinks[14] | https://www.wikidoc.org/index.php/Alkylbenzene | |
95b800e2afeab81649c3168c3487f7763878d4d3 | wikidoc | Allicin | Allicin
Allicin is a powerful antibacterial and anti-fungal compound obtained from garlic. Allicin is also the chemical constituent primarily responsible for the hot, burning flavor of fresh garlic.
Allicin is not present in garlic in its natural state. When garlic is chopped or otherwise damaged, the enzyme alliinase acts on the chemical alliin converting it into allicin. Alliin is an amino acid that does not build proteins.
Allicin is not a very stable compound. It degrades slowly upon standing and is rapidly destroyed by cooking. Allicin can be used for some medicinal purposes: it helps fighting arteriosclerosis, it has the ability to dissolve fats and it can also be used as an antioxidant to some extent. | Allicin
Template:Chembox new
Allicin is a powerful antibacterial and anti-fungal compound obtained from garlic. Allicin is also the chemical constituent primarily responsible for the hot, burning flavor of fresh garlic.
Allicin is not present in garlic in its natural state. When garlic is chopped or otherwise damaged, the enzyme alliinase acts on the chemical alliin converting it into allicin.[1] Alliin is an amino acid that does not build proteins.
Allicin is not a very stable compound. It degrades slowly upon standing and is rapidly destroyed by cooking. Allicin can be used for some medicinal purposes: it helps fighting arteriosclerosis, it has the ability to dissolve fats and it can also be used as an antioxidant to some extent.[2][3] | https://www.wikidoc.org/index.php/Allicin | |
034918a5649d120442e5c51198afde987a50419d | wikidoc | Prodine | Prodine
Please Take Over This Page and Apply to be Editor-In-Chief for this topic:
There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Prodine (Prisilidine, Nisentil) is an opioid analgesic that is an analogue of pethidine (meperidine).
There are two isomers of prodine, Alphaprodine and Betaprodine. Betaprodine is some 5x more potent than alphaprodine, but is metabolised more rapidly, and only alphaprodine was developed for medicinal use. It has similar activity to pethidine, but with a faster onset of action and shorter duration.
Alphaprodine was sold under several brand names, mainly Nisentil and Prisilidine. It was mainly used for pain relief in childbirth and dentistry, as well as for minor surgical procedures.
Prodine has similar effects to other opioids, and produces analgesia, sedation and euphoria. Side effects can include itching, nausea and potentially serious respiratory depression which can be life-threatening. Respiratory depression can be a problem with alphaprodine even at normal therapeutic doses. | Prodine
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Please Take Over This Page and Apply to be Editor-In-Chief for this topic:
There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [2] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
Prodine (Prisilidine, Nisentil) is an opioid analgesic that is an analogue of pethidine (meperidine).
There are two isomers of prodine, Alphaprodine and Betaprodine.[1] Betaprodine is some 5x more potent than alphaprodine,[2] but is metabolised more rapidly, and only alphaprodine was developed for medicinal use. It has similar activity to pethidine, but with a faster onset of action and shorter duration.[3]
Alphaprodine was sold under several brand names, mainly Nisentil and Prisilidine. It was mainly used for pain relief in childbirth[4] and dentistry,[5] as well as for minor surgical procedures.
Prodine has similar effects to other opioids, and produces analgesia, sedation and euphoria. Side effects can include itching, nausea and potentially serious respiratory depression which can be life-threatening. Respiratory depression can be a problem with alphaprodine even at normal therapeutic doses.[6] | https://www.wikidoc.org/index.php/Alphaprodine | |
e324fec0456ac0aec09507bf6f17e3d7e6f365ec | wikidoc | Alpidem | Alpidem
Alpidem (Ananxyl®) is an anxiolytic drug from the imidazopyridine family, related to the more well known sleeping medication zolpidem. Unlike zolpidem however, alpidem does not produce sedative effects at normal doses, and is instead used specifically for the treatment of anxiety.
Alpidem is a fairly recently introduced drug, and is not widely used. Alpidem acts selectively on the omega 1 (BZ1) receptor subtype, a benzodiazepine receptor. However the chemical structure of alpidem is not related to that of the benzodiazepines, and alpidem is thus sometimes referred to as a nonbenzodiazepine.
# Indications
Alpidem is generally prescribed to patients with moderate to severe anxiety. Most of these patients have exhibited either sensitivity or resistance to benzodiazepine therapy, and therefore switched to a non-benzodiazepine medication due to the reduced incidence of side effects relative to benzodiazepine drugs. Alpidem produces little or no sedative or hypnotic action at normal doses but may produce sedation when used at a high dose, and only has anticonvulsant actions at much higher doses than those used clinically for the treatment of anxiety.
# Dangers
Alpidem was withdrawn from the market in most of the world following reports of severe liver damage caused by Ananxyl, although other brands of alpidem may still be on sale in some countries. | Alpidem
Alpidem (Ananxyl®) is an anxiolytic drug from the imidazopyridine family, related to the more well known sleeping medication zolpidem. Unlike zolpidem however, alpidem does not produce sedative effects at normal doses, and is instead used specifically for the treatment of anxiety.[1][2]
Alpidem is a fairly recently introduced drug, and is not widely used. Alpidem acts selectively on the omega 1 (BZ1) receptor subtype, a benzodiazepine receptor.[3][4] However the chemical structure of alpidem is not related to that of the benzodiazepines, and alpidem is thus sometimes referred to as a nonbenzodiazepine.[5]
# Indications
Alpidem is generally prescribed to patients with moderate to severe anxiety.[6] Most of these patients have exhibited either sensitivity or resistance to benzodiazepine therapy, and therefore switched to a non-benzodiazepine medication due to the reduced incidence of side effects relative to benzodiazepine drugs.[7][8] Alpidem produces little or no sedative or hypnotic action at normal doses but may produce sedation when used at a high dose, and only has anticonvulsant actions at much higher doses than those used clinically for the treatment of anxiety.[9]
# Dangers
Alpidem was withdrawn from the market in most of the world following reports of severe liver damage caused by Ananxyl,[10][11] although other brands of alpidem may still be on sale in some countries. | https://www.wikidoc.org/index.php/Alpidem | |
52c0df8e31a43d5acd9b7dbc83e95cd7bff8f2fc | wikidoc | Amalgam | Amalgam
# Overview
An amalgam is an alloy of mercury with another metal. Most metals are soluble in mercury, but some (such as iron) are not. Amalgam also may be a solution of metal-like ion complexes, such as ammonium. Amalgams are commonly used in dental fillings.
# History of use
The earliest history of amalgam being used as a a dental restorative material is not very well established, but it has been reported that a silver paste had been used to restore a tooth in as early as 659 A.D. in China. In modern times, amalgam was placed by Auguste Taveau in France as early as 1826, although he had developed it in 1816.
The Crawcour brothers, two Frenchmen, brought amalgam to the United States in 1833, and in 1844 it was reported that 50% of all dental restorations placed in upstate New York consisted of amalgam. Prior to this, dentists had been restoring teeth using filling material such as stone chips, resin, cork, turpentine, gum, lead and gold leaf. The renowned physician Ambroise Paré (1510 – 1590) had used lead or cork to fill teeth.
Over the next 50 years, many different metal combinations had been tried, including the use of, among other things, platinum, cadmium, antimony and bismuth. In 1895, G. V. Black published a dental amalgam formula that provided for the most clinically acceptable performance, and his recipe remained unchanged for virtually 70 years.
In 1959, Dr. Wilmer Eames suggested a modification to the mercury-to-alloy ratio, recommending it be dropped from 8:5 to 1:1. The standard formula was again changed in 1963, when a superior amalgam consisting of a high-copper dispersion alloy was introduced. Although it was intially believed that this superiority was due to dispersion strengthening of the allow, it was later discovered that the improved strength of the amalgam was, in fact, a result of the additional copper forming a copper-tin phase that was less susceptible to corrosion than the tin-mercury phase in the earlier amalgam. This union of tin-mercury, now known as the gamma-2 phase, contributes to failure and is ideally allowed to rise during condensation of the amalgam while it is being placed in a tooth, to subsequently be removed when the amalgam is carved to achieve proper occlusal anatomy and functional occlusion.
# Modern use as a dental restoration
Amalgam is an "excellent and versatile restorative material" and is used in dentistry because of a number of reasons. It is inexpensive and relatively easy to use and manipulate during placement; it remains soft for a short time so it can be packed to fill any irregular volume, and then forms a hard compound. Amalgam possesses greater longevity than other direct restorative materials, such as composite; on average, most amalgam restorations serve for 10 to 12 years, whereas resin-based composites serve for about half that time. However, because of recent improvements in composite material science and a better understanding of the technique-sensitivity of placement, the length of composite survival has increased substantially.
The cost benefit analysis of the use of amalgam is often compared to that of resin-based composites because it would be the latter material that would generally be used as an alternative should the amalgam analysis prove unfavorable. There are many reasons why amalgam enjoys greater overall longevity than that of resin-based composites. Among these reasons are that composites are technique sensitive and require "extreme care" and "considerably greater number of exacting steps" in their proper placement. On the other hand, amalgam is "tolerant to a wide range of clinical placement conditions and moderately tolerant to the presence of moisture during placement.
Another important issue is the environment at the tooth-restoration margin. Whereas the elemental composition of amalgam serves as a bacteriostatic agent, TEGMA, the basic constituents in many resin-based composites, actually "encourages the growth of microorganisms." Because of this, recurrent marginal decay underneath resin-based composites "requires almost immediate removal, whereas those underneath amalgam restorations progress much more slowly."
Recurrent marginal decay is a very important factor in restoration failure, but more so in composite restorations. In the Casa Pia study in Portugal (1986-1989), 1,748 posterior restorations were placed and 177 (10.1%) of them failed during the course of the study. Recurrent marginal decay was the main reason for failure in both amalgam and composite restorations, accounting for 66% (32/48) and 88% (113/129), respectively. Polymerization shrinkage, the shrinkage that occurs during the composite curing process, has been implicated as the primary reason for postoperative marginal leakage.
It is because of these reasons and more that amalgam has been substantiated as a superior restorative material over resin-base composites. The New England Children's Amalgam Trial (NECAT), a randomized controlled trial, yielded results "consistent with previous reports suggesting that the longevity of amalgam is higher than that of resin-based compomer in primary teeth and composites in permanent teeth. Compomers were seven times as likly to require replacement and composites were seven times as likely to require repair.
There are circumstances in which composite serves better than amalgam; when amalgam is not indicated, or when a more conservative preparation would be beneficial, composite is the recommended restorative material. These situations would include small occlusal restorations, in which amalgam would require the removal of more sound tooth structure, as well as in "enamel sites beyond the height of contour."
Removal and replacement of amalgam restorations has traditionally been considered when "ditching" is present on the edges of the restoration. Ditching is "a deficiency of amalgam along the margin, preventing the margin of the cavity preparation from being flush... An area of ditching is also commonly referred to as a submarginal area and it requires removing tooth structure or replacing the amalgam to correct the situation."
# Dental amalgam controversy
Dental amalgam is a source of low-level exposure to mercury, and concerns have been raised about whether this poses a health hazard. Despite considerable investigation, no scientific evidence links it as a cause of clinically significant toxic effects, except for the rare local hypersensitivity reaction. The American Dental Association Council on Scientific Affairs concluded that both amalgam and composite materials are safe and effective for tooth restoration, and The National Institutes of Health has stated that amalgam fillings pose no personal health risk, and that replacement by non-amalgam fillings is not indicated. Recent random clinical trials have also established that amalgams are safe, finding no evidence of neurological harm or deleterious renal effects associated with their use in children after examining a period of 5–7 years following treatment. However, these studies did not address longer-term effects.
The preparation of amalgam could pose a potential health hazard to dental workers who work with mercury compounds in relatively high concentrations. Because mercury is a regulated waste in some countries, its disposal can be costly. | Amalgam
# Overview
An amalgam is an alloy of mercury with another metal. Most metals are soluble in mercury, but some (such as iron) are not. Amalgam also may be a solution of metal-like ion complexes, such as ammonium. Amalgams are commonly used in dental fillings.
# History of use
The earliest history of amalgam being used as a a dental restorative material is not very well established, but it has been reported that a silver paste had been used to restore a tooth in as early as 659 A.D. in China.[1] In modern times, amalgam was placed by Auguste Taveau in France as early as 1826,[2] although he had developed it in 1816.
The Crawcour brothers, two Frenchmen, brought amalgam to the United States in 1833,[3] and in 1844 it was reported that 50% of all dental restorations placed in upstate New York consisted of amalgam.[4] Prior to this, dentists had been restoring teeth using filling material such as stone chips, resin, cork, turpentine, gum, lead and gold leaf. The renowned physician Ambroise Paré (1510 – 1590) had used lead or cork to fill teeth.
Over the next 50 years, many different metal combinations had been tried, including the use of, among other things, platinum, cadmium, antimony and bismuth. In 1895, G. V. Black published a dental amalgam formula that provided for the most clinically acceptable performance, and his recipe remained unchanged for virtually 70 years.[5]
In 1959, Dr. Wilmer Eames suggested a modification to the mercury-to-alloy ratio, recommending it be dropped from 8:5 to 1:1.[6] The standard formula was again changed in 1963, when a superior amalgam consisting of a high-copper dispersion alloy was introduced.[7] Although it was intially believed that this superiority was due to dispersion strengthening of the allow, it was later discovered that the improved strength of the amalgam was, in fact, a result of the additional copper forming a copper-tin phase that was less susceptible to corrosion than the tin-mercury phase in the earlier amalgam.[8] This union of tin-mercury, now known as the gamma-2 phase, contributes to failure and is ideally allowed to rise during condensation of the amalgam while it is being placed in a tooth, to subsequently be removed when the amalgam is carved to achieve proper occlusal anatomy and functional occlusion.
# Modern use as a dental restoration
Amalgam is an "excellent and versatile restorative material"[9] and is used in dentistry because of a number of reasons. It is inexpensive and relatively easy to use and manipulate during placement; it remains soft for a short time so it can be packed to fill any irregular volume, and then forms a hard compound. Amalgam possesses greater longevity than other direct restorative materials, such as composite;[10] on average, most amalgam restorations serve for 10 to 12 years, whereas resin-based composites serve for about half that time.[11] However, because of recent improvements in composite material science and a better understanding of the technique-sensitivity of placement, the length of composite survival has increased substantially.[12]
The cost benefit analysis of the use of amalgam is often compared to that of resin-based composites because it would be the latter material that would generally be used as an alternative should the amalgam analysis prove unfavorable. There are many reasons why amalgam enjoys greater overall longevity than that of resin-based composites. Among these reasons are that composites are technique sensitive and require "extreme care"[13] and "considerably greater number of exacting steps"[14] in their proper placement. On the other hand, amalgam is "tolerant to a wide range of clinical placement conditions and moderately tolerant to the presence of moisture during placement.[15]
Another important issue is the environment at the tooth-restoration margin. Whereas the elemental composition of amalgam serves as a bacteriostatic agent, TEGMA, the basic constituents in many resin-based composites, actually "encourages the growth of microorganisms."[16] Because of this, recurrent marginal decay underneath resin-based composites "requires almost immediate removal, whereas those underneath amalgam restorations progress much more slowly."[17]
Recurrent marginal decay is a very important factor in restoration failure, but more so in composite restorations. In the Casa Pia study in Portugal (1986-1989), 1,748 posterior restorations were placed and 177 (10.1%) of them failed during the course of the study. Recurrent marginal decay was the main reason for failure in both amalgam and composite restorations, accounting for 66% (32/48) and 88% (113/129), respectively.[18] Polymerization shrinkage, the shrinkage that occurs during the composite curing process, has been implicated as the primary reason for postoperative marginal leakage.[19][20]
It is because of these reasons and more that amalgam has been substantiated as a superior restorative material over resin-base composites. The New England Children's Amalgam Trial (NECAT), a randomized controlled trial, yielded results "consistent with previous reports suggesting that the longevity of amalgam is higher than that of resin-based compomer in primary teeth[21][22] and composites in permanent teeth.[23][24] Compomers were seven times as likly to require replacement and composites were seven times as likely to require repair.[25]
There are circumstances in which composite serves better than amalgam; when amalgam is not indicated, or when a more conservative preparation would be beneficial, composite is the recommended restorative material. These situations would include small occlusal restorations, in which amalgam would require the removal of more sound tooth structure,[26] as well as in "enamel sites beyond the height of contour."[27]
Removal and replacement of amalgam restorations has traditionally been considered when "ditching" is present on the edges of the restoration. Ditching is "a deficiency of amalgam along the margin, preventing the margin of the cavity preparation from being flush... An area of ditching is also commonly referred to as a submarginal area and it requires removing tooth structure or replacing the amalgam to correct the situation."[28]
# Dental amalgam controversy
Dental amalgam is a source of low-level exposure to mercury, and concerns have been raised about whether this poses a health hazard. Despite considerable investigation, no scientific evidence links it as a cause of clinically significant toxic effects, except for the rare local hypersensitivity reaction. The American Dental Association Council on Scientific Affairs concluded that both amalgam and composite materials are safe and effective for tooth restoration,[29] and The National Institutes of Health has stated that amalgam fillings pose no personal health risk, and that replacement by non-amalgam fillings is not indicated.[30] Recent random clinical trials have also established that amalgams are safe, finding no evidence of neurological harm or deleterious renal effects associated with their use in children after examining a period of 5–7 years following treatment.[31][32] However, these studies did not address longer-term effects.[33]
The preparation of amalgam could pose a potential health hazard to dental workers who work with mercury compounds in relatively high concentrations. Because mercury is a regulated waste in some countries, its disposal can be costly. | https://www.wikidoc.org/index.php/Amalgam | |
ffa5963e38a540e49e89736d9fc9ecb55017a530 | wikidoc | Walking | Walking
# Overview
Walking is the main form of animal locomotion on land, distinguished from running and crawling. When carried out in shallow waters, it is usually described as wading and when performed over a steeply rising object or an obstacle it becomes scrambling or climbing. The word walking is derived from the Old English walkan (to roll).
Walking is generally distinguished from running in that only one foot at a time leaves contact with the ground: for humans and other bipeds running begins when both feet are off the ground with each step. (This distinction has the status of a formal requirement in competitive walking events, often resulting in disqualification even at the Olympic level.) For horses and other quadrupedal species, the running gaits may be numerous, and walking keeps three feet at a time on the ground.
The average human child achieves independent walking ability between nine and fifteen months old.
While not strictly bipedal, several primarily bipedal human gaits (where the long bones of the arms support at most a small fraction of the body's weight) are generally regarded as variants of walking. These include:
- Hand walking; an unusual form of locomotion, in which the walker moves primarily using his hands.
- walking on crutches (usually executed by alternating between standing on both legs, and rocking forward "on the crutches" (i.e., supported under the armpits by them);
- walking with one or two walking stick(s) or trekking poles (reducing the load on one or both legs, or supplementing the body's normal balancing mechanisms by also pushing against the ground through at least one arm that holds a long object);
- walking while holding on to a walker, a framework to aid with balance; and
- scrambling, using the arms (and hands or some other extension to the arms) not just as a backup to normal balance, but, as when walking on talus, to achieve states of balance that would be impossible or unstable when supported solely by the legs.
For humans, walking is the main form of transportation without a vehicle or riding animal. An average walking speed is about 5 km/h (3 mph), although this depends heavily on factors such as height, weight, age and terrain. A pedestrian is a walking person, in particular on a road (if available on the sidewalk/path/pavement).
# Biomechanics
Human walking is accomplished with a strategy called the double pendulum. During forward motion, the leg that leaves the ground swings forward from the hip. This sweep is the first pendulum. Then the leg strikes the ground with the heel and rolls through to the toe in a motion described as an inverted pendulum. The motion of the two legs is coordinated so that one foot or the other is always in contact with the ground. The process of walking recovers approximately sixty per cent of the energy used due to pendulum dynamics and ground reaction force.
The biomechanist Gracovetsky argues that the spine is the major agent in human locomotion. He bases his conclusions on the case of a man born without legs. The man was able to walk albeit slowly on his pelvis. Gracovetsky claims that however important to wellbeing, the function of legs is secondary in a strictly mechanical sense. Legs enable the spine to harvest the energy of gravity in an efficient manner. The legs act as long levers that transfer ground reaction force to the spine.
Lumbar motion during walking consists mostly of sideways rotation. Gracovetsky observes that fish use the same lateral motion to swim. He believes the mechanism first evolved in fish and was later adapted by amphibians, reptiles, mammals and humans to their respective modes of locomotion.
# As a leisure activity
Many people walk as a hobby, and in our post-industrial age it is often enjoyed as a form of exercise. Fitness walkers and others may use a pedometer to count their steps. The types of walking include bushwalking, racewalking, weight-walking, hillwalking, volksmarching, Nordic walking and hiking on long-distance paths. Sometimes people prefer to walk indoors using a treadmill. In some countries walking as a hobby is known as hiking (the typical North American term), rambling (a somewhat dated British expression, but remaining in use because it is enshrined in the title of the important Ramblers' Association), or tramping (the invariable term in New Zealand). Hiking is a subtype of walking, generally used to mean walking in nature areas on specially designated routes or trails, as opposed to in urban environments; however, hiking can also refer to any long-distance walk. More obscure terms for walking include "to go by Marrow-bone stage", "to take one's daily constitutional", "to ride Shank's pony" or "to go by Walker's bus."
The world's largest registration walking event is the International Four Days Marches Nijmegen. The annual Labor Day walk on Mackinac Bridge draws over sixty thousand participants. The Chesapeake Bay Bridge walk annually draws over fifty thousand participants. Walks are often organized as charity events with walkers seeking sponsors to raise money for a specific cause. Charity walks range in length from two mile or five km walks to as far as fifty miles (eighty km). The MS Challenge Walk is an example of a fifty mile walk which raises money to fight multiple sclerosis. The Oxfam Trailwalker is a one hundred km event.
In Britain, the Ramblers' Association is the biggest organisation that looks after the interests of walkers. A registered charity, it has 139 000 members.
# As transportation
Walking is also the most basic and common mode of transportation. People around the world use it to get to work, school, do their shopping and to wherever it is the most convenient way.
There has been a recent focus among urban planners in some communities to create pedestrian-friendly areas and roads, allowing commuting, shopping and recreation to be done on foot. Some communities are at least partially car-free, making them particularly supportive of walking and other modes of transportation. In the United States, the Active Living network is an example of a concerted effort to develop communities more friendly to walking and other physical activities.
On roads with no sidewalks, pedestrians should always walk facing the oncoming traffic for their own and other peoples' safety.
When distances are too great to be convenient, walking can be combined with other modes of transportation, such as cycling, public transport, car sharing, carpooling, hitchhiking, ride sharing, car rentals and taxis. These methods may be more efficient or desirable than private car ownership.
# In robotics
The first successful attempts at walking robots tended to have 6 legs. The number of legs was reduced as microprocessor technology advanced, and there are now a number of robots that can walk on 2 legs, albeit not nearly as well as a human being.
# Health benefits
Moe steps of walking per day are associated with reduced mortality.
Increasing walking by 2000 steps per day is associated with reduced mortality. In older women, walking at least 4000 total steps per day is associated with lower mortality.
Pedometers may help achieve goals. | Walking
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Walking is the main form of animal locomotion on land, distinguished from running and crawling. When carried out in shallow waters, it is usually described as wading and when performed over a steeply rising object or an obstacle it becomes scrambling or climbing. The word walking is derived from the Old English walkan (to roll).
Walking is generally distinguished from running in that only one foot at a time leaves contact with the ground: for humans and other bipeds running begins when both feet are off the ground with each step. (This distinction has the status of a formal requirement in competitive walking events, often resulting in disqualification even at the Olympic level.) For horses and other quadrupedal species, the running gaits may be numerous, and walking keeps three feet at a time on the ground.
The average human child achieves independent walking ability between nine and fifteen months old.
While not strictly bipedal, several primarily bipedal human gaits (where the long bones of the arms support at most a small fraction of the body's weight) are generally regarded as variants of walking. These include:
- Hand walking; an unusual form of locomotion, in which the walker moves primarily using his hands.
- walking on crutches (usually executed by alternating between standing on both legs, and rocking forward "on the crutches" (i.e., supported under the armpits by them);
- walking with one or two walking stick(s) or trekking poles (reducing the load on one or both legs, or supplementing the body's normal balancing mechanisms by also pushing against the ground through at least one arm that holds a long object);
- walking while holding on to a walker, a framework to aid with balance; and
- scrambling, using the arms (and hands or some other extension to the arms) not just as a backup to normal balance, but, as when walking on talus, to achieve states of balance that would be impossible or unstable when supported solely by the legs.
For humans, walking is the main form of transportation without a vehicle or riding animal. An average walking speed is about 5 km/h (3 mph), although this depends heavily on factors such as height, weight, age and terrain. A pedestrian is a walking person, in particular on a road (if available on the sidewalk/path/pavement).
# Biomechanics
Human walking is accomplished with a strategy called the double pendulum. During forward motion, the leg that leaves the ground swings forward from the hip. This sweep is the first pendulum. Then the leg strikes the ground with the heel and rolls through to the toe in a motion described as an inverted pendulum. The motion of the two legs is coordinated so that one foot or the other is always in contact with the ground. The process of walking recovers approximately sixty per cent of the energy used due to pendulum dynamics and ground reaction force. [2][3][4]
The biomechanist Gracovetsky argues that the spine is the major agent in human locomotion. He bases his conclusions on the case of a man born without legs. The man was able to walk albeit slowly on his pelvis. Gracovetsky claims that however important to wellbeing, the function of legs is secondary in a strictly mechanical sense. Legs enable the spine to harvest the energy of gravity in an efficient manner. The legs act as long levers that transfer ground reaction force to the spine. [5]
Lumbar motion during walking consists mostly of sideways rotation. [6] Gracovetsky observes that fish use the same lateral motion to swim. He believes the mechanism first evolved in fish and was later adapted by amphibians, reptiles, mammals and humans to their respective modes of locomotion.
# As a leisure activity
Many people walk as a hobby, and in our post-industrial age it is often enjoyed as a form of exercise. Fitness walkers and others may use a pedometer to count their steps. The types of walking include bushwalking, racewalking, weight-walking, hillwalking, volksmarching, Nordic walking and hiking on long-distance paths. Sometimes people prefer to walk indoors using a treadmill. In some countries walking as a hobby is known as hiking (the typical North American term), rambling (a somewhat dated British expression, but remaining in use because it is enshrined in the title of the important Ramblers' Association), or tramping (the invariable term in New Zealand). Hiking is a subtype of walking, generally used to mean walking in nature areas on specially designated routes or trails, as opposed to in urban environments; however, hiking can also refer to any long-distance walk. More obscure terms for walking include "to go by Marrow-bone stage", "to take one's daily constitutional", "to ride Shank's pony" or "to go by Walker's bus."
The world's largest registration walking event is the International Four Days Marches Nijmegen. The annual Labor Day walk on Mackinac Bridge draws over sixty thousand participants. The Chesapeake Bay Bridge walk annually draws over fifty thousand participants. Walks are often organized as charity events with walkers seeking sponsors to raise money for a specific cause. Charity walks range in length from two mile or five km walks to as far as fifty miles (eighty km). The MS Challenge Walk is an example of a fifty mile walk which raises money to fight multiple sclerosis. The Oxfam Trailwalker is a one hundred km event.
In Britain, the Ramblers' Association is the biggest organisation that looks after the interests of walkers. A registered charity, it has 139 000 members.
# As transportation
Walking is also the most basic and common mode of transportation. People around the world use it to get to work, school, do their shopping and to wherever it is the most convenient way.
There has been a recent focus among urban planners in some communities to create pedestrian-friendly areas and roads, allowing commuting, shopping and recreation to be done on foot. Some communities are at least partially car-free, making them particularly supportive of walking and other modes of transportation. In the United States, the Active Living network is an example of a concerted effort to develop communities more friendly to walking and other physical activities.
On roads with no sidewalks, pedestrians should always walk facing the oncoming traffic for their own and other peoples' safety.
When distances are too great to be convenient, walking can be combined with other modes of transportation, such as cycling, public transport, car sharing, carpooling, hitchhiking, ride sharing, car rentals and taxis. These methods may be more efficient or desirable than private car ownership.
# In robotics
The first successful attempts at walking robots tended to have 6 legs. The number of legs was reduced as microprocessor technology advanced, and there are now a number of robots that can walk on 2 legs, albeit not nearly as well as a human being.
# Health benefits
Moe steps of walking per day are associated with reduced mortality[1].
Increasing walking by 2000 steps per day is associated with reduced mortality[2]. In older women, walking at least 4000 total steps per day is associated with lower mortality.
Pedometers may help achieve goals[3][4][5].
# External links
- BMLwalker by Niko Troje
- Walking, by Henry David Thoreau
- London mapmovie showing what to see, where to walk and how to get there
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- ↑ Dwyer T, Pezic A, Sun C, Cochrane J, Venn A, Srikanth V; et al. (2015). "Objectively Measured Daily Steps and Subsequent Long Term All-Cause Mortality: The Tasped Prospective Cohort Study". PLoS One. 10 (11): e0141274. doi:10.1371/journal.pone.0141274. PMC 4633039. PMID 26536618.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (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}
- ↑ Kraus WE, Janz KF, Powell KE, Campbell WW, Jakicic JM, Troiano RP; et al. (2019). "Daily Step Counts for Measuring Physical Activity Exposure and Its Relation to Health". Med Sci Sports Exerc. 51 (6): 1206–1212. doi:10.1249/MSS.0000000000001932. PMC 6527133 Check |pmc= value (help). PMID 31095077.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
- ↑ de Vries HJ, Kooiman TJ, van Ittersum MW, van Brussel M, de Groot M (2016). "Do activity monitors increase physical activity in adults with overweight or obesity? A systematic review and meta-analysis". Obesity (Silver Spring). 24 (10): 2078–91. doi:10.1002/oby.21619. PMID 27670401.CS1 maint: Multiple names: authors list (link)
- ↑ Dasgupta K, Rosenberg E, Joseph L, Cooke AB, Trudeau L, Bacon SL; et al. (2017). "Physician step prescription and monitoring to improve ARTERial health (SMARTER): A randomized controlled trial in patients with type 2 diabetes and hypertension". Diabetes Obes Metab. 19 (5): 695–704. doi:10.1111/dom.12874. PMC 5412851. PMID 28074635.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
- ↑ McKay J, Wright A, Lowry R, Steele K, Ryde G, Mutrie N (2009). "Walking on prescription: the utility of a pedometer pack for increasing physical activity in primary care". Patient Educ Couns. 76 (1): 71–6. doi:10.1016/j.pec.2008.11.004. PMID 19097843.CS1 maint: Multiple names: authors list (link) | https://www.wikidoc.org/index.php/Ambulation | |
8c3430f9b3feee5fba4028e792122b1758464dc3 | wikidoc | Amidine | Amidine
Amidines are a class of oxoacid derivatives.
The oxoacid from which an amidine is derived must be of the form RnE(=O)OH, where R is a substituent. The −OH group is replaced by an −NH2 group and the =O group is replaced by =NR, giving amidines the general structure RnE(=NR)NR2.
When the parent oxoacid is a carboxylic acid, the resulting amidine is a carboxamidine, and has the following general structure:
Carboxamidines are frequently referred to simply as amidines, as they are the most commonly-encountered type of amidine in organic chemistry. The simplest amidine is acetamidine, CH3C(=NH)NH2.
Examples of amidines include DBU and diminazene. | Amidine
Amidines are a class of oxoacid derivatives.
The oxoacid from which an amidine is derived must be of the form RnE(=O)OH, where R is a substituent. The −OH group is replaced by an −NH2 group and the =O group is replaced by =NR, giving amidines the general structure RnE(=NR)NR2.
When the parent oxoacid is a carboxylic acid, the resulting amidine is a carboxamidine, and has the following general structure:
Carboxamidines are frequently referred to simply as amidines, as they are the most commonly-encountered type of amidine in organic chemistry. The simplest amidine is acetamidine, CH3C(=NH)NH2.
Examples of amidines include DBU and diminazene. | https://www.wikidoc.org/index.php/Amidine | |
10c96d0935b01df9885cdd72f058064832e22346 | wikidoc | Amitraz | Amitraz
Amitraz is an antiparasitic drug. Product names include Aazdieno, Acarac, Amitraze, Avartin, Baam, Edrizan, Maitac, Mitac, Mitaban, Triatox, Triatix, Vapcozin Taktic, Triazid, Topline, Tudy, Ectodex, Garial, Danicut, Ovidrex, Acadrex, Bumetran, and Ovasyn.
Amitraz is a triazapentadiene compound, a member of the amidine class. It is an insecticide and acaricide used to control red spider mites, leaf miners, scale insects, and aphids. On cotton it is used to control bollworms, white fly, and leaf worms. On animals it is used to control ticks, mites, lice and other animal pests. The EPA classifies Amitraz as Class III - slightly toxic.
It cannot be used on horses, because it can cause irreversible gut stasis. | Amitraz
Template:Chembox new
Amitraz is an antiparasitic drug. Product names include Aazdieno, Acarac, Amitraze, Avartin, Baam, Edrizan, Maitac, Mitac, Mitaban, Triatox, Triatix, Vapcozin Taktic, Triazid, Topline, Tudy, Ectodex, Garial, Danicut, Ovidrex, Acadrex, Bumetran, and Ovasyn.
Amitraz is a triazapentadiene compound, a member of the amidine class. It is an insecticide and acaricide used to control red spider mites, leaf miners, scale insects, and aphids. On cotton it is used to control bollworms, white fly, and leaf worms. On animals it is used to control ticks, mites, lice and other animal pests. The EPA classifies Amitraz as Class III - slightly toxic.
It cannot be used on horses, because it can cause irreversible gut stasis.
# External links
- Amitraz profile from EXTOXNET, maintained by Cornell University
Template:Organic-compound-stub
de:Amitraz | https://www.wikidoc.org/index.php/Amitraz | |
619871408df7b6d9107860f7e479c6a7fa7e2264 | wikidoc | Ammeter | Ammeter
An ammeter is a measuring instrument used to measure the electric current in a circuit. Electric currents are measured in amperes, hence the name. The word "ammeter" is commonly misspelled or mispronounced as "ampmeter" or "ameter" by some.
The earliest design is the D'Arsonval galvanometer or moving coil ammeter. It uses magnetic deflection, where current passing through a coil causes the coil to move in a magnetic field. The voltage drop across the coil is kept to a minimum to minimize resistance across the ammeter in any circuit into which it is inserted.
Moving iron ammeters use a piece or pieces of iron which move when acted upon by the electromagnetic force of a fixed coil of (usually heavy gauge) wire. This type of meter responds to both direct and alternating currents (as opposed to the moving coil ammeter, which works on direct current only).
To measure larger currents, a resistor called a shunt is placed in parallel with the meter. Most of the current flows through the shunt, and only a small fraction flows through the meter. This allows the meter to measure large currents. Traditionally, the meter used with a shunt has a full-scale deflection (FSD) of 50 mV, so shunts are typically designed to produce a voltage drop of 50 mV when carrying their full rated current.
Zero-center ammeters are used for applications requiring current to be measured with both polarities, common in scientific and industrial equipment. Zero-center ammeters are also commonly placed in series with a battery. In this application, the charging of the battery deflects the needle to one side of the scale (commonly, the right side) and the discharging of the battery deflects the needle to the other side.
Digital ammeter designs use an analog to digital converter (ADC) to measure the voltage across the shunt resistor; the digital display is calibrated to read the current through the shunt.
Since the ammeter shunt has a very low resistance, mistakenly wiring the ammeter in parallel with a voltage source will cause a short circuit, at best blowing a fuse, possibly damaging the instrument and wiring, and exposing an observer to injury. In AC circuits, a current transformer converts the magnetic field around a conductor into a small AC current, typically either 1 or 5 Amps at full rated current, that can be easily read by a meter. In a similar way, accurate AC/DC non-contact ammeters have been constructed using Hall effect magnetic field sensors. A portable hand-held clamp-on ammeter is a common tool for maintenance of industrial and commercial electrical equipment, which is temporarily clipped over a wire to measure current.
# Ammeter Schematic Symbol
The ammeter symbol (A) is shown in the diagram. | Ammeter
An ammeter is a measuring instrument used to measure the electric current in a circuit. Electric currents are measured in amperes, hence the name. The word "ammeter" is commonly misspelled or mispronounced as "ampmeter" or "ameter" by some.
The earliest design is the D'Arsonval galvanometer or moving coil ammeter. It uses magnetic deflection, where current passing through a coil causes the coil to move in a magnetic field. The voltage drop across the coil is kept to a minimum to minimize resistance across the ammeter in any circuit into which it is inserted.
Moving iron ammeters use a piece or pieces of iron which move when acted upon by the electromagnetic force of a fixed coil of (usually heavy gauge) wire. This type of meter responds to both direct and alternating currents (as opposed to the moving coil ammeter, which works on direct current only).
To measure larger currents, a resistor called a shunt is placed in parallel with the meter. Most of the current flows through the shunt, and only a small fraction flows through the meter. This allows the meter to measure large currents. Traditionally, the meter used with a shunt has a full-scale deflection (FSD) of 50 mV, so shunts are typically designed to produce a voltage drop of 50 mV when carrying their full rated current.
Zero-center ammeters are used for applications requiring current to be measured with both polarities, common in scientific and industrial equipment. Zero-center ammeters are also commonly placed in series with a battery. In this application, the charging of the battery deflects the needle to one side of the scale (commonly, the right side) and the discharging of the battery deflects the needle to the other side.
Digital ammeter designs use an analog to digital converter (ADC) to measure the voltage across the shunt resistor; the digital display is calibrated to read the current through the shunt.
Since the ammeter shunt has a very low resistance, mistakenly wiring the ammeter in parallel with a voltage source will cause a short circuit, at best blowing a fuse, possibly damaging the instrument and wiring, and exposing an observer to injury. In AC circuits, a current transformer converts the magnetic field around a conductor into a small AC current, typically either 1 or 5 Amps at full rated current, that can be easily read by a meter. In a similar way, accurate AC/DC non-contact ammeters have been constructed using Hall effect magnetic field sensors. A portable hand-held clamp-on ammeter is a common tool for maintenance of industrial and commercial electrical equipment, which is temporarily clipped over a wire to measure current.
# Ammeter Schematic Symbol
The ammeter symbol (A) is shown in the diagram. | https://www.wikidoc.org/index.php/Ammeter | |
03d88e5bd056539abfdb80fd0d70f6ab13eade3c | wikidoc | Ammonia | Ammonia
# Overview
Ammonia is a compound with the formula NH3. It is normally encountered as a gas with a characteristic pungent odor. Although ammonia contributes significantly to the nutritional needs of the planet, the gas itself is caustic and can cause serious health damage. The United States Occupational Safety and Health Administration (OSHA) has set a 15-minute exposure limit for gaseous ammonia of 35 ppm by volume in the environmental air and an 8-hour exposure limit of 25 ppm by volume. Exposure to very high concentrations of gaseous ammonia can result in lung damage and death. Although ammonia is regulated in the United States as a non-flammable gas, it still meets the definition of a material that is toxic by inhalation and requires a hazardous safety permit when transported in quantities greater than 13,248 L (3,500 gallons).
Ammonia used commercially is usually named anhydrous ammonia. This term emphasizes the absence of water. Because NH3 boils at -33 °C, the liquid must be stored under pressure or at low temperature. Its heat of vaporization is, however, sufficiently high that NH3 can be readily handled in ordinary beakers in a fume hood. "Household ammonia" or "ammonium hydroxide" is a solution of NH3 in water. The strength of such solutions is measured in units of baume (density), with 26 degrees baume (about 30 weight percent ammonia at 15.5 °C) being the typical high concentration commercial product. Household ammonia ranges in concentration from 5 to 10 weight percent ammonia. See Baumé scale.
# Structure and basic chemical properties
The ammonia molecule has a trigonal pyramid shape, as predicted by VSEPR theory. The nitrogen atom in the molecule has a lone electron pair, and ammonia acts as a base, a proton acceptor. This shape gives the molecule an overall dipole moment and makes it polar so that ammonia readily dissolves in water. In water a very small percentage of NH3 is converted into the ammonium cation (NH4+). Thus, the term ammonium hydroxide is a misnomer. The degree to which ammonia forms the ammonium ion increases upon lowering the pH of the solution— at "physiological" pH (~7), about 99% of the ammonia molecules are protonated. Temperature and salinity also affect the proportion of NH4+. NH4+ has the shape of a regular tetrahedron.
The main uses of ammonia are in the production of fertilizers, explosives, and synthesis of organonitrogen compounds. It is also the active ingredient in household glass cleaners. Ammonia is found in small quantities in the atmosphere, being produced from the putrefaction of nitrogenous animal and vegetable matter. Ammonia and ammonium salts are also found in small quantities in rainwater, while ammonium chloride (sal-ammoniac), and ammonium sulfate are found in volcanic districts; crystals of ammonium bicarbonate have been found in Patagonian guano. The kidneys secrete NH3 to neutralize excess acid. Ammonium salts also are found distributed through all fertile soil and in seawater. Substances containing ammonia, or that are similar to it, are called ammoniacal.
# History
Salts of ammonia have been known from very early times; thus the term Hammoniacus sal appears in the writings of Pliny the Elder, although it is not known whether the term is identical with the more modern sal-ammoniac.
In the form of sal-ammoniac, ammonia was known to the alchemists as early as the 13th century, being mentioned by Albertus Magnus. It was also used by dyers in the Middle Ages in the form of fermented urine to alter the colour of vegetable dyes. In the 15th century, Basilius Valentinus showed that ammonia could be obtained by the action of alkalis on sal-ammoniac. At a later period, when sal-ammoniac was obtained by distilling the hoofs and horns of oxen and neutralizing the resulting carbonate with hydrochloric acid, the name "spirit of hartshorn" was applied to ammonia.
Gaseous ammonia was first isolated by Joseph Priestley in 1774 and was termed by him alkaline air; however it was acquired by the alchemist Basil Valentine. Eleven years later in 1785, Claude Louis Berthollet ascertained its composition.
The Haber process to produce ammonia from the nitrogen in the air was developed by Fritz Haber and Carl Bosch in 1909 and patented in 1910. It was first used on an industrial scale by the Germans during World War I, following the allied blockade that cut off the supply of nitrates from Chile. The ammonia was used to produce explosives to sustain their war effort.
# Synthesis and production
Because of its many uses, ammonia is one of the most highly produced inorganic chemicals. Dozens of chemical plants worldwide produce ammonia. The worldwide ammonia production in 2004 was 109 million metric tonnes. The People's Republic of China produced 28.4% of the worldwide production followed by India with 8.6%, Russia with 8.4%, and the United States with 8.2%. About 80% or more of the ammonia produced is used for fertilizing agricultural crops.
Before the start of World War I most ammonia was obtained by the dry distillation of nitrogenous vegetable and animal waste products, including camel dung where it was distilled by the reduction of nitrous acid and nitrites with hydrogen; additionally, it was produced by the distillation of coal; and also by the decomposition of ammonium salts by alkaline hydroxides such as quicklime, the salt most generally used being the chloride (sal-ammoniac) thus:
Today, the typical modern ammonia-producing plant first converts natural gas (i.e. methane) or liquified petroleum gas (such gases are propane and butane) or petroleum naphtha into gaseous hydrogen. Starting with a natural gas feedstock, the processes used in producing the hydrogen are:
- The first step in the process entails removal of sulfur compounds from the feedstock, because sulfur deactivates the catalysts used in subsequent steps. Catalytic hydrogenation converts organosulfur compounds into gaseous hydrogen sulfide:
- The hydrogen sulfide is then removed by passing the gas through beds of zinc oxide where it is absorbed and converted to solid zinc sulfide:
- Catalytic steam reforming of the sulfur-free feedstock is then used to form hydrogen plus carbon monoxide:
- In the next step, the water gas shift reaction is used to convert the carbon monoxide into carbon dioxide and more hydrogen:
- The carbon dioxide is then removed either by absorption in aqueous ethanolamine solutions or by adsorption in pressure swing adsorbers (PSA) using proprietary solid adsorption media.
- The final step in producing the hydrogen is to use catalytic methanation to remove any small residual amounts of carbon monoxide or carbon dioxide from the hydrogen:
- To produce the desired end-product ammonia, the hydrogen is then catalytically reacted with nitrogen (derived from process air) to form anhydrous liquid ammonia. This step is known as the ammonia synthesis loop (also referred to as the Haber-Bosch process):
The steam reforming, shift conversion, carbon dioxide removal and methanation steps each operate at absolute pressures of about 25 to 35 bar, and the ammonia synthesis loop operates at absolute pressures ranging from 60 to 180 bar depending upon which proprietary design is used. There are many engineering and construction companies that offer proprietary designs for ammonia synthesis plants. Haldor Topsoe of Denmark, Lurgi AG of Germany, Uhde of Germany, and Kellogg, Brown and Root of the United States are among the most experienced companies in that field.
As the availability and usage of fossil fuel become problematic (see peak oil and climate change), the hydrogen needed for ammonia synthesis can be obtained from electrolysis or thermal chemical cracking of water. In such case, the heat needed for thermal cracking can be obtained from nuclear reaction while the electricity needed for electrolysis can be obtained from various renewable energy sources such as wind, solar, hydroelectricity, and various forms of ocean energy especially that of OTEC.
# Biosynthesis
In certain organisms, ammonia is produced from atmospheric N2 by enzymes called nitrogenases. The overall process is called nitrogen fixation. Although it is unlikely that biomimetic methods will be developed that are competitive with the Haber process, intense effort has been directed toward understanding the mechanism of biological nitrogen fixation. The scientific interest in this problem is motivated by the unusual structure of the active site of the enzyme, which consists of an Fe7MoS9 ensemble.
Ammonia is also a metabolic product of amino acid deamination. In humans, it is quickly converted to urea, which is much less toxic. This urea is a major component of the dry weight of urine.
# Properties
Ammonia is a colorless gas with a characteristic pungent smell similar to human urine, as the urine contains an amount of ammonia in it. It is lighter than air, its density being 0.589 times that of air. It is easily liquefied due to the strong hydrogen bonding between molecules; the liquid boils at -33.3 °C, and solidifies at -77.7 °C to a mass of white crystals. Liquid ammonia possesses strong ionizing powers (ε = 22), and solutions of salts in liquid ammonia have been much studied. Liquid ammonia has a very high standard enthalpy change of vaporization (23.35 kJ/mol, cf. water 40.65 kJ/mol, methane 8.19 kJ/mol, phosphine 14.6 kJ/mol) and can therefore be used in laboratories in non-insulated vessels at room temperature, even though it is well above its boiling point.
It is miscible with water. All the ammonia contained in an aqueous solution of the gas may be expelled by boiling. The aqueous solution of ammonia is basic. The maximum concentration of ammonia in water (a saturated solution) has a density of 0.880 g /cm³ and is often known as '.880 Ammonia'. Ammonia does not burn readily or sustain combustion, except under narrow fuel to air mixtures from 15-25% air. When mixed with oxygen, it burns with a pale yellowish-green flame. At high temperature and in the presence of a suitable catalyst, ammonia is decomposed into its constituent elements. Chlorine catches fire when passed into ammonia, forming nitrogen and hydrochloric acid; unless the ammonia is present in excess, the highly explosive nitrogen trichloride (NCl3) is also formed.
The ammonia molecule readily undergoes nitrogen inversion at room temperature - that is, the nitrogen atom passes through the plane of symmetry of the three hydrogen atoms; a useful analogy is an umbrella turning itself inside out in a strong wind. The energy barrier to this inversion is 24.7 kJ/mol in ammonia, and the resonance frequency is 23.79 GHz, corresponding to microwave radiation of a wavelength of 1.260 cm. The absorption at this frequency was the first microwave spectrum to be observed.
## Formation of salts
One of the most characteristic properties of ammonia is its power of combining directly with acids to form salts; thus with hydrochloric acid it forms ammonium chloride (sal-ammoniac); with nitric acid, ammonium nitrate, etc. However perfectly dry ammonia will not combine with perfectly dry hydrogen chloride, a gas, moisture being necessary to bring about the reaction.
The salts produced by the action of ammonia on acids are known as the ammonium salts and all contain the ammonium ion (NH4+).
## Acidity
Although ammonia is well-known as a base, it can also act as an extremely weak acid. It is a protic substance, and is capable of dissociation into the amide (NH2−) ion, for example when solid lithium nitride is added to liquid ammonia, forming a lithium amide solution:
This is a Brønsted-Lowry acid-base reaction in which ammonia is acting as an acid.
## Formation of other compounds
Ammonia can act as a nucleophile in substitution reactions. Amines can be formed by the reaction of ammonia with alkyl halides, although the resulting –NH2 group is also nucleophilic and secondary and tertiary amines are often formed as by-products. Using an excess of ammonia helps minimise multiple substitution, and neutralises the hydrogen halide formed. Methylamine is prepared commercially by the reaction of ammonia with chloromethane, and the reaction of ammonia with 2-bromopropanoic acid has been used to prepare racemic alanine in 70% yield. Ethanolamine is prepared by a ring-opening reaction with ethylene oxide: the reaction is sometimes allowed to go further to produce diethanolamine and triethanolamine.
Amides can be prepared by the reaction of ammonia with a number of carboxylic acid derivatives. Acyl chlorides are the most reactive, but the ammonia must be present in at least a twofold excess to neutralise the hydrogen chloride formed. Esters and anhydrides also react with ammonia to form amides. Ammonium salts of carboxylic acids can be dehydrated to amides so long as there are no thermally sensitive groups present: temperatures of 150–200 °C are required.
The hydrogen in ammonia is capable of replacement by metals, thus magnesium burns in the gas with the formation of magnesium nitride Mg3N2, and when the gas is passed over heated sodium or potassium, sodamide, NaNH2, and potassamide, KNH2, are formed. Where necessary in substitutive nomenclature, IUPAC recommendations prefer the name azane to ammonia: hence chloramine would be named chloroazane in substitutive nomenclature, not chloroammonia.
## Ammonia as a ligand
Ammonia can act as a ligand in transition metal complexes. It is a pure σ-donor, in the middle of the spectrochemical series, and shows intermediate hard-soft behaviour. For historical reasons, ammonia is named ammine in the nomenclature of coordination compounds. Some notable ammine complexes include:
- Tetraamminecopper(II), 2+, a characteristic dark blue complex formed by adding ammonia to solution of copper(II) salts.
- Diamminesilver(I), +, the active species in Tollens' reagent. Formation of this complex can also help to distinguish between precipitates of the different silver halides: AgCl is soluble in dilute (2M) ammonia solution, AgBr is only soluble in concentrated ammonia solution while AgI is insoluble in aqueous solution of ammonia.
Ammine complexes of chromium(III) were known in the late 19th century, and formed the basis of Alfred Werner's theory of coordination compounds. Werner noted that only two isomers (fac- and mer-) of the complex could be formed, and concluded that the ligands must be arranged around the metal ion at the vertices of an octahedron. This has since been confirmed by X-ray crystallography.
An ammine ligand bound to a metal ion is markedly more acidic than a free ammonia molecule, although deprotonation in aqueous solution is still rare. One example is the Calomel reaction, where the resulting amidomercury(II) compound is highly insoluble.
# Uses
## Nitric Acid production
The most important single use of ammonia is in the production of nitric acid. A mixture of one part ammonia to nine parts air is passed over a platinum gauze catalyst at 850 °C, whereupon the ammonia is oxidized to nitric oxide.
The catalyst is essential, as the normal oxidation (or combustion) of ammonia gives dinitrogen and water: the production of nitric oxide is an example of kinetic control. As the gas mixture cools to 200–250 °C, the nitric oxide is in turn oxidized by the excess of oxygen present in the mixture, to give nitrogen dioxide. This is reacted with water to give nitric acid for use in the production of fertilizers and explosives.
## Universal Indicator
Ammonia solution is also used as universal indicator that could be used to test for different gases that require a universal indicator solution to show the gases were present.
## Fertilizer
In addition to serving as a fertilizer ingredient, ammonia can also be used directly as a fertilizer by forming a solution with irrigation water, without additional chemical processing. This later use allows the continuous growing of nitrogen dependent crops such as maize (corn) without crop rotation but this type of use leads to poor soil health.
## Refrigeration
Ammonia's thermodynamic properties made it one of the refrigerants commonly used in refrigeration units prior to the discovery of dichlorodifluoromethane in 1928, also known as Freon or R12.
But ammonia is toxic, gaseous, irritant, and corrosive to copper alloys, and over a kilo is needed for even a miniature fridge. With an ammonia refrigerant, the ever present risk of an escape brings with it a risk to life. However data on ammonia escapes has shown this to be an extremely small risk in practice, and there is consequently no control on the use of ammonia refrigeration in densely populated areas and buildings in almost all jurisdictions in the world.
Its use in domestic refrigeration has been mostly replaced by CFCs and HFCs in the first world, which are more or less non-toxic and non-flammable, and butane and propane in the 3rd world, which despite their high flammability do not seem to have produced any significant level of accidents. Ammonia has continued to be used for miniature and multifuel fridges, such as minibars and caravan fridges.
These ammonia absorption cycle domestic refrigerators do not use compression and expansion cycles, but are driven by temperature differences. However the energy efficiency of such refrigerators is relatively low. Today the smallest refrigerators mostly use solid state peltier thermopile heat pumps rather than the ammonia absorption cycle.
Ammonia continues to be used as a refrigerant in large industrial processes such as bulk icemaking and industrial food processing. Since the implication of haloalkanes being major contributors to ozone depletion, ammonia is again seeing increasing use as a refrigerant.
## Disinfectant
It is also sometimes added to drinking water along with chlorine to form chloramine, a disinfectant. Unlike chlorine on its own, chloramine does not combine with organic (carbon containing) materials to form carcinogenic halomethanes such as chloroform. However, chlorine and ammonia should never be mixed in an uncontrolled environment because they cause a chemical reaction that releases toxic gas. See Safety precautions for more information.
## Fuel
Liquid ammonia was used as the fuel of the rocket airplane, the X-15. Although not as powerful as other fuels, it left no soot in the reusable rocket engine, and has about the same density as the oxidizer, liquid oxygen, which simplified the aircraft's keeping the same center of gravity in flight. Anhydrous ammonia is a practical clean (CO2-free) and renewable fuel which can be and has been used to replace fossil fuel in powering internal combustion engines. In 1981 a Canadian company converted a 1981 Chevrolet Impala to run on an ammonia fuel.
## Cigarettes
During the 1960s, tobacco companies such as
Brown & Williamson and Philip Morris began using ammonia in cigarettes. The addition of ammonia serves to enhance the delivery of nicotine into the blood stream. As a result, the reinforcement effect of the nicotine was enhanced, increasing its addictive ability without actually increasing the portion of nicotine.
# Ammonia's role in biologic systems and human disease
Ammonia is an important source of nitrogen for living systems. Although atmospheric nitrogen abounds, few living creatures are capable of utilizing this nitrogen. Nitrogen is required for the synthesis of amino acids, which are the building blocks of protein. Some plants rely on ammonia and other nitrogenous wastes incorporated into the soil by decaying matter. Others, such as nitrogen-fixing legumes, benefit from symbiotic relationships with rhizobia which create ammonia from atmospheric nitrogen.
Ammonia also plays a role in both normal and abnormal animal physiology. Ammonia is created through normal amino acid metabolism and is toxic in high concentrations. The liver converts ammonia to urea through a series of reactions known as the urea cycle. Liver dysfunction, such as that seen in cirrhosis, may lead to elevated amounts of ammonia in the blood (hyperammonemia). Likewise, defects in the enzymes responsible for the urea cycle, such as ornithine transcarbamylase, lead to hyperammonemia. Hyperammonemia contributes to the confusion and coma of hepatic encephalopathy as well as the neurologic disease common in people with urea cycle defects and organic acidurias.
Ammonia is important for normal animal acid/base balance. After formation of ammonium from glutamine, α-ketoglutarate may be degraded to produce two molecules of bicarbonate which are then available as buffers for dietary acids. Ammonium is excreted in the urine resulting in net acid loss. Ammonia may itself diffuse across the renal tubules, combine with a hydrogen ion, and thus allow for further acid excretion.
## Theoretical role in alternative biochemistry
Ammonia has been proposed as a possible replacement for water as a bodily solvent in the theoretical alternative biochemistries of lifeforms that do not use carbon for cellular structure and water as a solvent to dissolve bodily solutes and allow essential parts of metabolic processes to occur. It is suggested that ammonia would be most favorable for lifeforms that live in temperatures lower than the freezing point of water.
# Liquid ammonia as a solvent
Liquid ammonia is the best-known and most widely studied non-aqueous ionizing solvent. Its most conspicuous property is its ability to dissolve alkali metals to form highly coloured, electrically conducting solutions containing solvated electrons. Apart from these remarkable solutions, much of the chemistry in liquid ammonia can be classified by analogy with related reactions in aqueous solutions. Comparison of the physical properties of NH3 with those of water shows that NH3 has the lower melting point, boiling point, density, viscosity, dielectric constant and electrical conductivity; this is due at least in part to the weaker H bonding in NH3 and the fact that such bonding cannot form cross-linked networks since each NH3 molecule has only 1 lone-pair of electrons compared with 2 for each H2O molecule. The ionic self-dissociation constant of liquid NH3 at −50 °C is approx. 10-33 mol2·l-2.
## Solubility of salts
Liquid ammonia is an ionizing solvent, although less so than water, and dissolves a range of ionic compounds including many nitrates, nitrites, cyanides and thiocyanates. Most ammonium salts are soluble, and these salts act as acids in liquid ammonia solutions. The solubility of halide salts increases from fluoride to iodide. A saturated solution of ammonium nitrate contains 0.83 mol solute per mole of ammonia, and has a vapour pressure of less than 1 bar even at 25 °C.
## Solutions of metals
Liquid ammonia will dissolve the alkali metals and other electropositive metals such as calcium, strontium, barium, europium and ytterbium. At low concentrations (<0.06 mol/L), deep blue solutions are formed: these contain metal cations and solvated electrons, free electrons which are surrounded by a cage of ammonia molecules.
These solutions are very useful as strong reducing agents. At higher concentrations, the solutions are metallic in appearance and in electrical conductivity. At low temperatures, the two types of solution can coexist as immiscible phases.
## Redox properties of liquid ammonia
The range of thermodynamic stability of liquid ammonia solutions is very narrow, as the potential for oxidation to dinitrogen, E° (N2 + 6NH4+ + 6e− Template:Unicode 8NH3), is only +0.04 V. In practice, both oxidation to dinitrogen and reduction to dihydrogen are slow. This is particularly true of reducing solutions: the solutions of the alkali metals mentioned above are stable for several days, slowly decomposing to the metal amide and dihydrogen. Most studies involving liquid ammonia solutions are done in reducing conditions: although oxidation of liquid ammonia is usually slow, there is still a risk of explosion, particularly if transition metal ions are present as possible catalysts.
# Detection and determination
Ammonia and ammonium salts can be readily detected, in very minute traces, by the addition of Nessler's solution, which gives a distinct yellow coloration in the presence of the least trace of ammonia or ammonium salts. Sulfur sticks are burnt to detect small leaks in industrial ammonia refrigeration systems. Larger quantities can be detected by warming the salts with a caustic alkali or with quicklime, when the characteristic smell of ammonia will be at once apparent. The amount of ammonia in ammonium salts can be estimated quantitatively by distillation of the salts with sodium or potassium hydroxide, the ammonia evolved being absorbed in a known volume of standard sulfuric acid and the excess of acid then determined volumetrically; or the ammonia may be absorbed in hydrochloric acid and the ammonium chloride so formed precipitated as ammonium hexachloroplatinate, (NH4)2PtCl6.
## Interstellar space
Ammonia was first detected in interstellar space in 1968, based on microwave emissions from the direction of the galactic core. This was the first polyatomic molecule to be so detected.
The sensitivity of the molecule to a broad range of excitations and the ease with which it can be observed in a number of regions has made ammonia one of the most important molecules for studies of molecular clouds. The relative intensity of the ammonia lines can be used to measure the temperature of the emitting medium.
The following isotopic species of ammonia have been detected:
The detection of triply-deuterated ammonia was considered a surprise as deuterium is relatively scarce. It is thought that the low-temperature conditions allow this molecule to survive and accumulate. The ammonia molecule has also been detected in the atmospheres of the gas giant planets, including Jupiter, along with other gases like methane, hydrogen, and helium. The interior of Saturn may include frozen crystals of ammonia.
# Safety precautions
## Toxicity and storage information
The toxicity of ammonia solutions does not usually cause problems for humans and other mammals, as a specific mechanism exists to prevent its build-up in the bloodstream. Ammonia is converted to carbamoyl phosphate by the enzyme carbamoyl phosphate synthase, and then enters the urea cycle to be either incorporated into amino acids or excreted in the urine. However fish and amphibians lack this mechanism, as they can usually eliminate ammonia from their bodies by direct excretion. Ammonia even at dilute concentrations is highly toxic to aquatic animals, and for this reason it is classified as dangerous for the environment. Ammonium compounds should never be allowed to come in contact with bases (unless an intended and contained reaction), as dangerous quantities of ammonia gas could be released.
## Household use
Solutions of ammonia (5–10% by weight) are used as household cleaners, particularly for glass. These solutions are irritating to the eyes and mucous membranes (respiratory and digestive tracts), and to a lesser extent the skin. They should never be mixed with chlorine-containing products or strong oxidants, for example household bleach, as a variety of toxic and carcinogenic compounds are formed (e.g., chloramine, hydrazine, and chlorine gas). Ammonia and sodium hypochlorite react to form a number of products, depending on the temperature, concentration, and how they are mixed. . The main reaction is chlorination of ammonia, first giving chloramine (NH2Cl), then NHCl2 and finally nitrogen trichloride (NCl3). These materials are very irritating to eyes and lungs and are toxic above certain concentrations.
## Laboratory use of ammonia solutions
The hazards of ammonia solutions depend on the concentration: "dilute" ammonia solutions are usually 5–10% by weight (25% by weight. A 25% (by weight) solution has a density of 0.907 g/cm³, and a solution which has a lower density will be more concentrated. The European Union classification of ammonia solutions is given in the table.
The ammonia vapour from concentrated ammonia solutions is severely irritating to the eyes and the respiratory tract, and these solutions should only be handled in a fume hood. Saturated ("0.880") solutions can develop a significant pressure inside a closed bottle in warm weather, and the bottle should be opened with care: this is not usually a problem for 25% ("0.900") solutions.
Ammonia solutions should not be mixed with halogens, as toxic and/or explosive products are formed. Prolonged contact of ammonia solutions with silver, mercury or iodide salts can also lead to explosive products: such mixtures are often formed in qualitative chemical analysis, and should be acidified and diluted before disposal once the test is completed.
## Laboratory use of anhydrous ammonia (gas or liquid)
Anhydrous ammonia is classified as toxic (T) and dangerous for the environment (N). The gas is flammable (autoignition temperature: 651 °C) and can form explosive mixtures with air (16–25%). The permissible exposure limit (PEL) in the United States is 50 ppm (35 mg/m3), while the IDLH concentration is estimated at 300 ppm. Repeated exposure to ammonia lowers the sensitivity to the smell of the gas: normally the odour is detectable at concentrations of less than 0.5 ppm, but desensitized individuals may not detect it even at concentrations of 100 ppm. Anhydrous ammonia corrodes copper- and zinc-containing alloys, and so brass fittings should not be used for handling the gas. Liquid ammonia can also attack rubber and certain plastics.
Ammonia reacts violently with the halogens, and causes the explosive polymerization of ethylene oxide. It also forms explosive compounds with compounds of gold, silver, mercury, germanium or tellurium, and with stibine. Violent reactions have also been reported with acetaldehyde, hypochlorite solutions, potassium ferricyanide and peroxides. | Ammonia
Template:Chembox new
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Ammonia is a compound with the formula NH3. It is normally encountered as a gas with a characteristic pungent odor. Although ammonia contributes significantly to the nutritional needs of the planet, the gas itself is caustic and can cause serious health damage. The United States Occupational Safety and Health Administration (OSHA) has set a 15-minute exposure limit for gaseous ammonia of 35 ppm by volume in the environmental air and an 8-hour exposure limit of 25 ppm by volume.[1] Exposure to very high concentrations of gaseous ammonia can result in lung damage and death.[1] Although ammonia is regulated in the United States as a non-flammable gas, it still meets the definition of a material that is toxic by inhalation and requires a hazardous safety permit when transported in quantities greater than 13,248 L (3,500 gallons).[2]
Ammonia used commercially is usually named anhydrous ammonia. This term emphasizes the absence of water. Because NH3 boils at -33 °C, the liquid must be stored under pressure or at low temperature. Its heat of vaporization is, however, sufficiently high that NH3 can be readily handled in ordinary beakers in a fume hood. "Household ammonia" or "ammonium hydroxide" is a solution of NH3 in water. The strength of such solutions is measured in units of baume (density), with 26 degrees baume (about 30 weight percent ammonia at 15.5 °C) being the typical high concentration commercial product.[3] Household ammonia ranges in concentration from 5 to 10 weight percent ammonia. See Baumé scale.
# Structure and basic chemical properties
The ammonia molecule has a trigonal pyramid shape, as predicted by VSEPR theory. The nitrogen atom in the molecule has a lone electron pair, and ammonia acts as a base, a proton acceptor. This shape gives the molecule an overall dipole moment and makes it polar so that ammonia readily dissolves in water. In water a very small percentage of NH3 is converted into the ammonium cation (NH4+). Thus, the term ammonium hydroxide is a misnomer. The degree to which ammonia forms the ammonium ion increases upon lowering the pH of the solution— at "physiological" pH (~7), about 99% of the ammonia molecules are protonated. Temperature and salinity also affect the proportion of NH4+. NH4+ has the shape of a regular tetrahedron.
The main uses of ammonia are in the production of fertilizers, explosives, and synthesis of organonitrogen compounds. It is also the active ingredient in household glass cleaners. Ammonia is found in small quantities in the atmosphere, being produced from the putrefaction of nitrogenous animal and vegetable matter. Ammonia and ammonium salts are also found in small quantities in rainwater, while ammonium chloride (sal-ammoniac), and ammonium sulfate are found in volcanic districts; crystals of ammonium bicarbonate have been found in Patagonian guano. The kidneys secrete NH3 to neutralize excess acid.[4] Ammonium salts also are found distributed through all fertile soil and in seawater. Substances containing ammonia, or that are similar to it, are called ammoniacal.
# History
Salts of ammonia have been known from very early times; thus the term Hammoniacus sal[5] appears in the writings of Pliny the Elder, although it is not known whether the term is identical with the more modern sal-ammoniac.[5]
In the form of sal-ammoniac, ammonia was known to the alchemists as early as the 13th century, being mentioned by Albertus Magnus.[6] It was also used by dyers in the Middle Ages in the form of fermented urine[6] to alter the colour of vegetable dyes. In the 15th century, Basilius Valentinus showed that ammonia could be obtained by the action of alkalis on sal-ammoniac. At a later period, when sal-ammoniac was obtained by distilling the hoofs and horns of oxen and neutralizing the resulting carbonate with hydrochloric acid, the name "spirit of hartshorn" was applied to ammonia.[6]
Gaseous ammonia was first isolated by Joseph Priestley in 1774 and was termed by him alkaline air; however it was acquired by the alchemist Basil Valentine.[7] Eleven years later in 1785, Claude Louis Berthollet ascertained its composition.
The Haber process to produce ammonia from the nitrogen in the air was developed by Fritz Haber and Carl Bosch in 1909 and patented in 1910. It was first used on an industrial scale by the Germans during World War I,[8] following the allied blockade that cut off the supply of nitrates from Chile. The ammonia was used to produce explosives to sustain their war effort.[9]
# Synthesis and production
Because of its many uses, ammonia is one of the most highly produced inorganic chemicals. Dozens of chemical plants worldwide produce ammonia. The worldwide ammonia production in 2004 was 109 million metric tonnes.[10] The People's Republic of China produced 28.4% of the worldwide production followed by India with 8.6%, Russia with 8.4%, and the United States with 8.2%.[10] About 80% or more of the ammonia produced is used for fertilizing agricultural crops.[10]
Before the start of World War I most ammonia was obtained by the dry distillation[11] of nitrogenous vegetable and animal waste products, including camel dung where it was distilled[9] by the reduction of nitrous acid and nitrites with hydrogen; additionally, it was produced by the distillation of coal;[9] and also by the decomposition of ammonium salts by alkaline hydroxides[12] such as quicklime, the salt most generally used being the chloride (sal-ammoniac) thus:
Today, the typical modern ammonia-producing plant first converts natural gas (i.e. methane) or liquified petroleum gas (such gases are propane and butane) or petroleum naphtha into gaseous hydrogen. Starting with a natural gas feedstock, the processes used in producing the hydrogen are:
- The first step in the process entails removal of sulfur compounds from the feedstock, because sulfur deactivates the catalysts used in subsequent steps. Catalytic hydrogenation converts organosulfur compounds into gaseous hydrogen sulfide:
- The hydrogen sulfide is then removed by passing the gas through beds of zinc oxide where it is absorbed and converted to solid zinc sulfide:
- Catalytic steam reforming of the sulfur-free feedstock is then used to form hydrogen plus carbon monoxide:
- In the next step, the water gas shift reaction is used to convert the carbon monoxide into carbon dioxide and more hydrogen:
- The carbon dioxide is then removed either by absorption in aqueous ethanolamine solutions or by adsorption in pressure swing adsorbers (PSA) using proprietary solid adsorption media.
- The final step in producing the hydrogen is to use catalytic methanation to remove any small residual amounts of carbon monoxide or carbon dioxide from the hydrogen:
- To produce the desired end-product ammonia, the hydrogen is then catalytically reacted with nitrogen (derived from process air) to form anhydrous liquid ammonia. This step is known as the ammonia synthesis loop (also referred to as the Haber-Bosch process):
The steam reforming, shift conversion, carbon dioxide removal and methanation steps each operate at absolute pressures of about 25 to 35 bar, and the ammonia synthesis loop operates at absolute pressures ranging from 60 to 180 bar depending upon which proprietary design is used. There are many engineering and construction companies that offer proprietary designs for ammonia synthesis plants. Haldor Topsoe of Denmark, Lurgi AG of Germany, Uhde of Germany, and Kellogg, Brown and Root of the United States are among the most experienced companies in that field.[13]
As the availability and usage of fossil fuel become problematic (see peak oil and climate change), the hydrogen needed for ammonia synthesis can be obtained from electrolysis or thermal chemical cracking of water. In such case, the heat needed for thermal cracking can be obtained from nuclear reaction while the electricity needed for electrolysis can be obtained from various renewable energy sources such as wind, solar, hydroelectricity, and various forms of ocean energy especially that of OTEC.
# Biosynthesis
In certain organisms, ammonia is produced from atmospheric N2 by enzymes called nitrogenases. The overall process is called nitrogen fixation. Although it is unlikely that biomimetic methods will be developed that are competitive with the Haber process, intense effort has been directed toward understanding the mechanism of biological nitrogen fixation. The scientific interest in this problem is motivated by the unusual structure of the active site of the enzyme, which consists of an Fe7MoS9 ensemble.
Ammonia is also a metabolic product of amino acid deamination. In humans, it is quickly converted to urea, which is much less toxic. This urea is a major component of the dry weight of urine.
# Properties
Ammonia is a colorless gas with a characteristic pungent smell similar to human urine, as the urine contains an amount of ammonia in it. It is lighter than air, its density being 0.589 times that of air. It is easily liquefied due to the strong hydrogen bonding between molecules; the liquid boils at -33.3 °C, and solidifies at -77.7 °C to a mass of white crystals. Liquid ammonia possesses strong ionizing powers (ε = 22), and solutions of salts in liquid ammonia have been much studied. Liquid ammonia has a very high standard enthalpy change of vaporization (23.35 kJ/mol, cf. water 40.65 kJ/mol, methane 8.19 kJ/mol, phosphine 14.6 kJ/mol) and can therefore be used in laboratories in non-insulated vessels at room temperature, even though it is well above its boiling point.
It is miscible with water. All the ammonia contained in an aqueous solution of the gas may be expelled by boiling. The aqueous solution of ammonia is basic. The maximum concentration of ammonia in water (a saturated solution) has a density of 0.880 g /cm³ and is often known as '.880 Ammonia'. Ammonia does not burn readily or sustain combustion, except under narrow fuel to air mixtures from 15-25% air. When mixed with oxygen, it burns with a pale yellowish-green flame. At high temperature and in the presence of a suitable catalyst, ammonia is decomposed into its constituent elements. Chlorine catches fire when passed into ammonia, forming nitrogen and hydrochloric acid; unless the ammonia is present in excess, the highly explosive nitrogen trichloride (NCl3) is also formed.
The ammonia molecule readily undergoes nitrogen inversion at room temperature - that is, the nitrogen atom passes through the plane of symmetry of the three hydrogen atoms; a useful analogy is an umbrella turning itself inside out in a strong wind. The energy barrier to this inversion is 24.7 kJ/mol in ammonia, and the resonance frequency is 23.79 GHz, corresponding to microwave radiation of a wavelength of 1.260 cm. The absorption at this frequency was the first microwave spectrum to be observed.[14]
## Formation of salts
One of the most characteristic properties of ammonia is its power of combining directly with acids to form salts; thus with hydrochloric acid it forms ammonium chloride (sal-ammoniac); with nitric acid, ammonium nitrate, etc. However perfectly dry ammonia will not combine with perfectly dry hydrogen chloride, a gas, moisture being necessary to bring about the reaction.[15]
The salts produced by the action of ammonia on acids are known as the ammonium salts and all contain the ammonium ion (NH4+).
## Acidity
Although ammonia is well-known as a base, it can also act as an extremely weak acid. It is a protic substance, and is capable of dissociation into the amide (NH2−) ion, for example when solid lithium nitride is added to liquid ammonia, forming a lithium amide solution:
This is a Brønsted-Lowry acid-base reaction in which ammonia is acting as an acid.
## Formation of other compounds
Ammonia can act as a nucleophile in substitution reactions. Amines can be formed by the reaction of ammonia with alkyl halides, although the resulting –NH2 group is also nucleophilic and secondary and tertiary amines are often formed as by-products. Using an excess of ammonia helps minimise multiple substitution, and neutralises the hydrogen halide formed. Methylamine is prepared commercially by the reaction of ammonia with chloromethane, and the reaction of ammonia with 2-bromopropanoic acid has been used to prepare racemic alanine in 70% yield. Ethanolamine is prepared by a ring-opening reaction with ethylene oxide: the reaction is sometimes allowed to go further to produce diethanolamine and triethanolamine.
Amides can be prepared by the reaction of ammonia with a number of carboxylic acid derivatives. Acyl chlorides are the most reactive, but the ammonia must be present in at least a twofold excess to neutralise the hydrogen chloride formed. Esters and anhydrides also react with ammonia to form amides. Ammonium salts of carboxylic acids can be dehydrated to amides so long as there are no thermally sensitive groups present: temperatures of 150–200 °C are required.
The hydrogen in ammonia is capable of replacement by metals, thus magnesium burns in the gas with the formation of magnesium nitride Mg3N2, and when the gas is passed over heated sodium or potassium, sodamide, NaNH2, and potassamide, KNH2, are formed. Where necessary in substitutive nomenclature, IUPAC recommendations prefer the name azane to ammonia: hence chloramine would be named chloroazane in substitutive nomenclature, not chloroammonia.
## Ammonia as a ligand
Ammonia can act as a ligand in transition metal complexes. It is a pure σ-donor, in the middle of the spectrochemical series, and shows intermediate hard-soft behaviour. For historical reasons, ammonia is named ammine in the nomenclature of coordination compounds. Some notable ammine complexes include:
- Tetraamminecopper(II), [Cu(NH3)4]2+, a characteristic dark blue complex formed by adding ammonia to solution of copper(II) salts.
- Diamminesilver(I), [Ag(NH3)2]+, the active species in Tollens' reagent. Formation of this complex can also help to distinguish between precipitates of the different silver halides: AgCl is soluble in dilute (2M) ammonia solution, AgBr is only soluble in concentrated ammonia solution while AgI is insoluble in aqueous solution of ammonia.
Ammine complexes of chromium(III) were known in the late 19th century, and formed the basis of Alfred Werner's theory of coordination compounds. Werner noted that only two isomers (fac- and mer-) of the complex [CrCl3(NH3)3] could be formed, and concluded that the ligands must be arranged around the metal ion at the vertices of an octahedron. This has since been confirmed by X-ray crystallography.
An ammine ligand bound to a metal ion is markedly more acidic than a free ammonia molecule, although deprotonation in aqueous solution is still rare. One example is the Calomel reaction, where the resulting amidomercury(II) compound is highly insoluble.
# Uses
## Nitric Acid production
The most important single use of ammonia is in the production of nitric acid. A mixture of one part ammonia to nine parts air is passed over a platinum gauze catalyst at 850 °C, whereupon the ammonia is oxidized to nitric oxide.
The catalyst is essential, as the normal oxidation (or combustion) of ammonia gives dinitrogen and water: the production of nitric oxide is an example of kinetic control. As the gas mixture cools to 200–250 °C, the nitric oxide is in turn oxidized by the excess of oxygen present in the mixture, to give nitrogen dioxide. This is reacted with water to give nitric acid for use in the production of fertilizers and explosives.
## Universal Indicator
Ammonia solution is also used as universal indicator that could be used to test for different gases that require a universal indicator solution to show the gases were present.
## Fertilizer
In addition to serving as a fertilizer ingredient, ammonia can also be used directly as a fertilizer by forming a solution with irrigation water, without additional chemical processing. This later use allows the continuous growing of nitrogen dependent crops such as maize (corn) without crop rotation but this type of use leads to poor soil health.
## Refrigeration
Ammonia's thermodynamic properties made it one of the refrigerants commonly used in refrigeration units prior to the discovery of dichlorodifluoromethane[16] in 1928, also known as Freon or R12.
But ammonia is toxic, gaseous, irritant, and corrosive to copper alloys, and over a kilo is needed for even a miniature fridge. With an ammonia refrigerant, the ever present risk of an escape brings with it a risk to life. However data on ammonia escapes has shown this to be an extremely small risk in practice, and there is consequently no control on the use of ammonia refrigeration in densely populated areas and buildings in almost all jurisdictions in the world.
Its use in domestic refrigeration has been mostly replaced by CFCs and HFCs in the first world, which are more or less non-toxic and non-flammable, and butane and propane in the 3rd world, which despite their high flammability do not seem to have produced any significant level of accidents. Ammonia has continued to be used for miniature and multifuel fridges, such as minibars and caravan fridges.
These ammonia absorption cycle domestic refrigerators do not use compression and expansion cycles, but are driven by temperature differences. However the energy efficiency of such refrigerators is relatively low. Today the smallest refrigerators mostly use solid state peltier thermopile heat pumps rather than the ammonia absorption cycle.
Ammonia continues to be used as a refrigerant in large industrial processes such as bulk icemaking and industrial food processing. Since the implication of haloalkanes being major contributors to ozone depletion, ammonia is again seeing increasing use as a refrigerant.
## Disinfectant
It is also sometimes added to drinking water along with chlorine to form chloramine, a disinfectant. Unlike chlorine on its own, chloramine does not combine with organic (carbon containing) materials to form carcinogenic halomethanes such as chloroform. However, chlorine and ammonia should never be mixed in an uncontrolled environment because they cause a chemical reaction that releases toxic gas. See Safety precautions for more information.
## Fuel
Liquid ammonia was used as the fuel of the rocket airplane, the X-15. Although not as powerful as other fuels, it left no soot in the reusable rocket engine, and has about the same density as the oxidizer, liquid oxygen, which simplified the aircraft's keeping the same center of gravity in flight. Anhydrous ammonia is a practical clean (CO2-free) and renewable fuel which can be and has been used to replace fossil fuel in powering internal combustion engines.[17] In 1981 a Canadian company converted a 1981 Chevrolet Impala to run on an ammonia fuel.[18][19]
## Cigarettes
During the 1960s, tobacco companies such as
Brown & Williamson and Philip Morris began using ammonia in cigarettes. The addition of ammonia serves to enhance the delivery of nicotine into the blood stream. As a result, the reinforcement effect of the nicotine was enhanced, increasing its addictive ability without actually increasing the portion of nicotine.[20]
# Ammonia's role in biologic systems and human disease
Ammonia is an important source of nitrogen for living systems. Although atmospheric nitrogen abounds, few living creatures are capable of utilizing this nitrogen. Nitrogen is required for the synthesis of amino acids, which are the building blocks of protein. Some plants rely on ammonia and other nitrogenous wastes incorporated into the soil by decaying matter. Others, such as nitrogen-fixing legumes, benefit from symbiotic relationships with rhizobia which create ammonia from atmospheric nitrogen.[21]
Ammonia also plays a role in both normal and abnormal animal physiology. Ammonia is created through normal amino acid metabolism and is toxic in high concentrations.[22] The liver converts ammonia to urea through a series of reactions known as the urea cycle. Liver dysfunction, such as that seen in cirrhosis, may lead to elevated amounts of ammonia in the blood (hyperammonemia). Likewise, defects in the enzymes responsible for the urea cycle, such as ornithine transcarbamylase, lead to hyperammonemia. Hyperammonemia contributes to the confusion and coma of hepatic encephalopathy as well as the neurologic disease common in people with urea cycle defects and organic acidurias.[23]
Ammonia is important for normal animal acid/base balance. After formation of ammonium from glutamine, α-ketoglutarate may be degraded to produce two molecules of bicarbonate which are then available as buffers for dietary acids. Ammonium is excreted in the urine resulting in net acid loss. Ammonia may itself diffuse across the renal tubules, combine with a hydrogen ion, and thus allow for further acid excretion.[24]
## Theoretical role in alternative biochemistry
Ammonia has been proposed as a possible replacement for water as a bodily solvent in the theoretical alternative biochemistries of lifeforms that do not use carbon for cellular structure and water as a solvent to dissolve bodily solutes and allow essential parts of metabolic processes to occur. It is suggested that ammonia would be most favorable for lifeforms that live in temperatures lower than the freezing point of water.[25]
# Liquid ammonia as a solvent
Liquid ammonia is the best-known and most widely studied non-aqueous ionizing solvent. Its most conspicuous property is its ability to dissolve alkali metals to form highly coloured, electrically conducting solutions containing solvated electrons. Apart from these remarkable solutions, much of the chemistry in liquid ammonia can be classified by analogy with related reactions in aqueous solutions. Comparison of the physical properties of NH3 with those of water shows that NH3 has the lower melting point, boiling point, density, viscosity, dielectric constant and electrical conductivity; this is due at least in part to the weaker H bonding in NH3 and the fact that such bonding cannot form cross-linked networks since each NH3 molecule has only 1 lone-pair of electrons compared with 2 for each H2O molecule. The ionic self-dissociation constant of liquid NH3 at −50 °C is approx. 10-33 mol2·l-2.
## Solubility of salts
Liquid ammonia is an ionizing solvent, although less so than water, and dissolves a range of ionic compounds including many nitrates, nitrites, cyanides and thiocyanates. Most ammonium salts are soluble, and these salts act as acids in liquid ammonia solutions. The solubility of halide salts increases from fluoride to iodide. A saturated solution of ammonium nitrate contains 0.83 mol solute per mole of ammonia, and has a vapour pressure of less than 1 bar even at 25 °C.
## Solutions of metals
Liquid ammonia will dissolve the alkali metals and other electropositive metals such as calcium, strontium, barium, europium and ytterbium. At low concentrations (<0.06 mol/L), deep blue solutions are formed: these contain metal cations and solvated electrons, free electrons which are surrounded by a cage of ammonia molecules.
These solutions are very useful as strong reducing agents. At higher concentrations, the solutions are metallic in appearance and in electrical conductivity. At low temperatures, the two types of solution can coexist as immiscible phases.
## Redox properties of liquid ammonia
The range of thermodynamic stability of liquid ammonia solutions is very narrow, as the potential for oxidation to dinitrogen, E° (N2 + 6NH4+ + 6e− Template:Unicode 8NH3), is only +0.04 V. In practice, both oxidation to dinitrogen and reduction to dihydrogen are slow. This is particularly true of reducing solutions: the solutions of the alkali metals mentioned above are stable for several days, slowly decomposing to the metal amide and dihydrogen. Most studies involving liquid ammonia solutions are done in reducing conditions: although oxidation of liquid ammonia is usually slow, there is still a risk of explosion, particularly if transition metal ions are present as possible catalysts.
# Detection and determination
Ammonia and ammonium salts can be readily detected, in very minute traces, by the addition of Nessler's solution, which gives a distinct yellow coloration in the presence of the least trace of ammonia or ammonium salts. Sulfur sticks are burnt to detect small leaks in industrial ammonia refrigeration systems. Larger quantities can be detected by warming the salts with a caustic alkali or with quicklime, when the characteristic smell of ammonia will be at once apparent. The amount of ammonia in ammonium salts can be estimated quantitatively by distillation of the salts with sodium or potassium hydroxide, the ammonia evolved being absorbed in a known volume of standard sulfuric acid and the excess of acid then determined volumetrically; or the ammonia may be absorbed in hydrochloric acid and the ammonium chloride so formed precipitated as ammonium hexachloroplatinate, (NH4)2PtCl6.
## Interstellar space
Ammonia was first detected in interstellar space in 1968, based on microwave emissions from the direction of the galactic core.[26] This was the first polyatomic molecule to be so detected.
The sensitivity of the molecule to a broad range of excitations and the ease with which it can be observed in a number of regions has made ammonia one of the most important molecules for studies of molecular clouds.[27] The relative intensity of the ammonia lines can be used to measure the temperature of the emitting medium.
The following isotopic species of ammonia have been detected:
The detection of triply-deuterated ammonia was considered a surprise as deuterium is relatively scarce. It is thought that the low-temperature conditions allow this molecule to survive and accumulate.[28] The ammonia molecule has also been detected in the atmospheres of the gas giant planets, including Jupiter, along with other gases like methane, hydrogen, and helium. The interior of Saturn may include frozen crystals of ammonia.[29]
# Safety precautions
## Toxicity and storage information
The toxicity of ammonia solutions does not usually cause problems for humans and other mammals, as a specific mechanism exists to prevent its build-up in the bloodstream. Ammonia is converted to carbamoyl phosphate by the enzyme carbamoyl phosphate synthase, and then enters the urea cycle to be either incorporated into amino acids or excreted in the urine. However fish and amphibians lack this mechanism, as they can usually eliminate ammonia from their bodies by direct excretion. Ammonia even at dilute concentrations is highly toxic to aquatic animals, and for this reason it is classified as dangerous for the environment. Ammonium compounds should never be allowed to come in contact with bases (unless an intended and contained reaction), as dangerous quantities of ammonia gas could be released.
## Household use
Solutions of ammonia (5–10% by weight) are used as household cleaners, particularly for glass. These solutions are irritating to the eyes and mucous membranes (respiratory and digestive tracts), and to a lesser extent the skin. They should never be mixed with chlorine-containing products or strong oxidants, for example household bleach, as a variety of toxic and carcinogenic compounds are formed (e.g., chloramine, hydrazine, and chlorine gas). Ammonia and sodium hypochlorite react to form a number of products, depending on the temperature, concentration, and how they are mixed. [30]. The main reaction is chlorination of ammonia, first giving chloramine (NH2Cl), then NHCl2 and finally nitrogen trichloride (NCl3). These materials are very irritating to eyes and lungs and are toxic above certain concentrations.
## Laboratory use of ammonia solutions
The hazards of ammonia solutions depend on the concentration: "dilute" ammonia solutions are usually 5–10% by weight (<5.62 mol/L); "concentrated" solutions are usually prepared at >25% by weight. A 25% (by weight) solution has a density of 0.907 g/cm³, and a solution which has a lower density will be more concentrated. The European Union classification of ammonia solutions is given in the table.
The ammonia vapour from concentrated ammonia solutions is severely irritating to the eyes and the respiratory tract, and these solutions should only be handled in a fume hood. Saturated ("0.880") solutions can develop a significant pressure inside a closed bottle in warm weather, and the bottle should be opened with care: this is not usually a problem for 25% ("0.900") solutions.
Ammonia solutions should not be mixed with halogens, as toxic and/or explosive products are formed. Prolonged contact of ammonia solutions with silver, mercury or iodide salts can also lead to explosive products: such mixtures are often formed in qualitative chemical analysis, and should be acidified and diluted before disposal once the test is completed.
## Laboratory use of anhydrous ammonia (gas or liquid)
Anhydrous ammonia is classified as toxic (T) and dangerous for the environment (N). The gas is flammable (autoignition temperature: 651 °C) and can form explosive mixtures with air (16–25%). The permissible exposure limit (PEL) in the United States is 50 ppm (35 mg/m3), while the IDLH concentration is estimated at 300 ppm. Repeated exposure to ammonia lowers the sensitivity to the smell of the gas: normally the odour is detectable at concentrations of less than 0.5 ppm, but desensitized individuals may not detect it even at concentrations of 100 ppm. Anhydrous ammonia corrodes copper- and zinc-containing alloys, and so brass fittings should not be used for handling the gas. Liquid ammonia can also attack rubber and certain plastics.
Ammonia reacts violently with the halogens, and causes the explosive polymerization of ethylene oxide. It also forms explosive compounds with compounds of gold, silver, mercury, germanium or tellurium, and with stibine. Violent reactions have also been reported with acetaldehyde, hypochlorite solutions, potassium ferricyanide and peroxides. | https://www.wikidoc.org/index.php/Ammonia | |
26c99e512d0222f600a24735f7648bb8daacc719 | wikidoc | Colitis | Colitis
Synonyms and keywords: Colitis, Proctocolitis, Proctitis, Enterocolitis.
# Overview
Colitis is the inflammation of the colon, that can be either acute or chronic. Colitis may be caused by microorganisms such as Chlamydia trachomatis, Neisseria gonorrhoeae, Shigella dysenteriae, HSV, allergy (food protein-induced allergic proctocolitis), drugs (NSAIDs) and radiation. Colitis may co-exist with enteritis (inflammation of the small bowel), proctitis (inflammation of the rectum) or both. The symptoms of colitis such as diarrhea especially bloody diarrhea and abdominal pain (which may be mild) are seen in all forms of colitis. Colitis may be fulminant with a rapid downhill clinical course. In addition to the diarrhea, fever, and anemia may be reported. The patient with fulminant colitis has severe abdominal pain and presents a clinical picture similar to that of septicemia, where shock is present. Treatment of colitis depends on the etiology. It may include the elimination of cows-milk protein or other food allergens from the diet, administration of antibiotics and general anti-inflammatory medications such as mesalamine or its derivatives, steroids, or one of a number of other drugs that ameliorate inflammation. The mainstay of therapy for infectious colitis is antimicrobial therapy. A common antibiotic regimen in treatment of patients with colitis is a combination of ceftriaxone and doxycycline. Supportive therapies such as correction of dehydration and anemia, and reducing the intake of carbohydrates, lactose products, soft drinks, and caffeine is often done for most patients with colitis. Irritable bowel syndrome (spastic colitis or spastic colon) has been called colitis, causing confusion despite colitis not being a feature of the disease. Immune mediated colitis is the experimental name in animal studies of ulcerative colitis. It is a synonym of ulcerative colitis, but it should not be used as a synonym when referring to ulcerative colitis.
# Classification
There is no established classification system for colitis. However, it may be classified based on etiology, age and duration of symptom.
## Classification by etiology
## Classification by Anatomy
Colitis may co-exist with inflammation involving other parts of the gastrointestinal tract. It can be classified based on anatomy into:
- Proctitis: When it involves the rectum
- Colitis: When it involves the inflammation is limited to the colon
- Proctocolitis: When it involves the rectum and colon (usually the distal part of the colon 12cm to 15cm above the anus (sigmoid colon)
- Enterocolitis: When it involves the small intestine in addition to the colon
### Schematic of Anatomical Classification of Colitis
## Classification by Age
- Infantile (first six months of life)
- Adult
## Classification by duration of symptoms
- Acute: Less than three months.
- Chronic: Longer than three months. Often months to years.
# Differential Diagnosis
The differential diagnosis of colitis can be classified into two categories according to age group. A work up for colitis must include the following differentials:
## Differential diagnosis in Infants
- Swallowed maternal blood syndrome
- Anorectal fissure
- Necrotizing enterocolitis especially in preterm babies
- Vitamin K dependent hemorrhage
- Other coagulopathies: (hereditary such as coagulation factor deficiency or acquired such as disseminated intravascular coagulopathy)
- Intussusception
- Upper Gastrointestinal Infections
- Enteritis
- Meckel diverticulum
- Intestinal duplication cysts
- Vascular malformations
- Inflammatory bowel disease(early onset)
- Hirschsprung disease complicated by enterocolitis
- Volvulus
- Gastro-duodenal ulcers
- Gastrointestinal duplication cyst
- Liver disease with clotting factor deficiency
- Lymphonodular hyperplasia
## Differential diagnosis in Adults
- Colorectal malignancy
- Crohn's disease
- Behcet's disease
- Arteriovenous malformation
- Diverticulosis
- Enteritis
- Coagulopathy
- Systemic lupus erythematosus(SLE)
- Cytomegalovirus colitis
## Differentiating Between Different Types of Colitis
The symptoms of colitis such as diarrhea especially bloody diarrhea and abdominal pain are seen are seen in all forms of colitis. The table below differentiates among the common causes of colitis:
# Causes
## Common Causes
Common causes of proctocolitis include infectious agents such as Chlamydia trachomatis (which causes lymphogranuloma venereum), Neisseria gonorrhoeae, HSV, Shigella dysenteriae and Campylobacter species. It can also be allergic (e.g. food protein-induced proctocolitis), idiopathic (e.g. microscopic colitis), vascular (e.g. ischemic colitis), or autoimmune (e.g. inflammatory bowel disease).
## Causes by Organ System
## Causes in Alphabetical Order
- Aganglionic megacolon
- Albinism
- Alosetron
- Alpha 1-antitrypsin deficiency
- Ampicillin Oral
- Ankylosing spondylitis
- Auranofin
- Autistic enterocolitis
- Azithromycin
- Aztreonam Injection
- Bacillary dysentery
- Bacterial gastroenteritis
- Balantidium coli
- Behcet disease
- Campylobacter jejuni
- Cap polyposis
- Cefaclor
- Cefadroxil
- Cefamandole Nafate Injection
- Cefazolin Sodium Injection
- Cefepime
- Cefepime Injection
- Cefoperazone Sodium Injection
- Cefotaxime Sodium Injection
- Cefotetan Disodium Injection
- Cefoxitin Sodium Injection
- Cefpodoxime
- Ceftazidime
- Ceftazidime Injection
- Ceftizoxime Sodium Injection
- Ceftriaxone Sodium Injection
- Cefuroxime Sodium Injection
- Cephalexin
- Cephalosporin
- Cephradine Oral
- Chemical colitis
- Chlamydia trachomatis
- Cidofovir
- Cilansetron
- Clindamycin
- Clostridium difficile
- Co-amoxiclav
- Colitis ulcerosa
- Collagenous colitis
- Colonic ischemia
- Common variable immunodeficiency
- Corticosteroid
- Crohn's disease
- Cryptosporidiosis
- Cytomegalovirus
- Darifenacin
- Dental braces
- Desogestrel and Ethinyl Estradiol
- Dicloxacillin
- Dirithromycin
- Diversion colitis
- Diverticulosis
- Enoxacin
- Entamoeba histolytica
- Ertapenem
- Erythromycin and Sulfisoxazole
- Escherichia coli O157:H7
- EVAR
- Flucytosine
- Gerson diet
- Giardiasis
- Glycopyrrolate
- Hyoscyamine
- Idelalisib
- Imipenem and Cilastatin Sodium Injection
- Infectious colitis
- Inflammatory bowel disease
- Intestinal ischemia
- Ipilimumab
- Irritable bowel syndrome
- Ischemic colitis
- Isosporiasis
- Ixabepilone
- Lanthanum
- Levofloxacin Oral
- Lincomycin hydrochloride
- Linezolid
- Lomefloxacin
- Loracarbef
- Lymphocytic colitis
- Lysinuric protein intolerance
- Methotrexate
- Miconazole Injection
- Microscopic colitis
- Milk allergy
- Moxifloxacin
- Multiple organ dysfunction syndrome
- Nafcillin Sodium Injection
- Neisseria gonorrhoeae
- Neonatal necrotizing enterocolitis
- Nivolumab
- Norfloxacin
- Ofloxacin injection
- Oxacillin Sodium Injection
- Oxcarbazepine
- Oxybutynin
- Peginterferon alfa-2a
- Penicillin
- Pergolide
- Pigbel
- Piperacillin sodium injection
- Pramipexole
- Prednisolone
- Primary sclerosing cholangitis
- Procyclidine
- Propantheline
- Protein losing enteropathy
- Pseudoephedrine
- Pseudomembranous colitis
- Quinolone
- Radiation colitis
- Radiation proctitis
- Ramosetron
- Reserpine
- Salmonella
- Schistosoma
- Scleroderma
- Sepsis
- Shigella
- Solifenacin
- Solitary rectal ulcer syndrome
- Soy protein
- Sparfloxacin
- Strongyloides stercoralis
- Syphilis
- Tegaserod
- Toxic megacolon
- Treponema pallidum
- Typhlitis
- Ulcerative colitis
- Vasculitis
- Yersinia enterocolitica
## Life Threatening Causes
Example include toxic megacolon, ischemic colitis, infectious colitis such as escherichia coli O157:H7 and shigella.
# Screening
There is insufficient evidence to recommend routine screening of sexual partners of patients with sexually transmitted enteric pathogens.
# Diagnosis
## History and Symptoms
- Symptoms of proctitis include anorectal pain, tenesmus, or rectal discharge.
- Symptoms of proctocolitis include fatigue, weight loss, anorectal pain, tenesmus, rectal discharge, diarrhea or abdominal cramps.
## Laboratory Findings
Laboratory findings consistent with the diagnosis of proctitis include:
- Stool examination: Detection of blood or fecal polymorphonuclear leukocytes using gram-stained smear of any anorectal exudate from anoscopic or anal examination.
- Microbiology workup: NAAT of rectal lesions for HSV, NAAT for Neisseria gonorrhea, syphilis serology, NAAT for Chlamydia trachomatis, and NAAT for Mycoplasma genitalium in case of persistence of symptoms after receiving the recommended treatment. CMV and other opportunistic infections may be evaluated in immunosuppressed individuals as HIV/AIDS.
- An elevated erythrocyte sedimentation rate (ESR) is one typical finding in the acute exacerbation of proctocolitis.
## Other Imaging Findings
### Colonoscopy
Anoscopy or sigmoidoscopy may be helpful in the diagnosis of proctocolitis. Findings on an sigmoidoscopy suggestive of proctocolitis include inflammation of the colonic mucosa extending to 12 cm above the anus and rectal ulcers.
# Treatment
## Medical Therapy
Acute proctocolitis among individuals with receptive anal exposure is often sexually-transmitted. Empiric antibiotic treatment should be started while awaiting for the results of laboratory tests for
patients presenting with anorectal exudate on anoscopy or positive Gram-stained smear of anorectal exudate or secretions polymorphonuclear leukocytes or if anoscopy or Gram stain is not available.
### Recommended Regimen for Acute Proctitis
Ceftriaxone 500 mg IM in a single dose
plus
Doxycycline 100 mg orally 2 times/day for 7 days
- Doxycycline course is continued to 100 mg orally 2 times/day for 21 days in case of perianal or mucosal ulcers, bloody discharge, or tenesmus and a positive rectal chlamydia test.
- For individuals weighing ≥150 kg, 1 g of ceftriaxone is given.
- Patients presenting with mucosal or perianal ulcers or bloody diarrhea with positive NAAT for chlamydia should receive empiric therapy for Lymphogranuloma Venereum (LGV) with a prolonged course of doxycycline 100 mg orally 2 times/day for 3 weeks.
- Patients presenting with painful perianal ulcers or mucosal ulcers on anoscopy should also receive empiric treatment for genital herpes.
- Herpes proctocolitis and LGV occur predominantly among HIV/AIDS patients; hence empiric treatment in those patients should cover genital herpes and LGV.
## Surgery
Surgical intervention is not recommended for the management of proctocolitis.
# Primary Prevention
As proctocolitis can be a sexually transmitted disease, effective measures for the primary prevention of proctocolitis include:
- Counseling on safe sex practices
- Avoiding contact with feces during sexual intercourse
- Hand washing after handing objects or materials that have been in contact with the anal area (i.e., sex toys or barriers) and after touching the anal area.
# Secondary Prevention
Effective measures for the secondary prevention of proctocolitis include:
- Abstinence from sexual activity until the patient and their partners are successfully treated (i.e., completion of a 7-day regimen and resolution of symptoms)
- Sexual partners with individuals treated for chlamydia or gonorrhea <60 days before the onset of symptoms should receive evaluation and empiric treatment of the causative infection
- Testing for other sexually-transmitted diseases
- In case of proctocolitis caused by chlamydia or Neisseria gonorrhea, retesting for the causative organism is recommended 3 months after completion of treatment. | Colitis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M.Umer Tariq [2]; Maham Khan [3]; Ogheneochuko Ajari, MB.BS, MS [4]; Rim Halaby, M.D. [5]; Qasim Salau, M.B.B.S., FMCPaed [6]; Mohamed Riad, M.D.[7]
Synonyms and keywords: Colitis, Proctocolitis, Proctitis, Enterocolitis.
# Overview
Colitis is the inflammation of the colon, that can be either acute or chronic. Colitis may be caused by microorganisms such as Chlamydia trachomatis, Neisseria gonorrhoeae, Shigella dysenteriae, HSV, allergy (food protein-induced allergic proctocolitis), drugs (NSAIDs) and radiation. Colitis may co-exist with enteritis (inflammation of the small bowel), proctitis (inflammation of the rectum) or both. The symptoms of colitis such as diarrhea especially bloody diarrhea and abdominal pain (which may be mild) are seen in all forms of colitis. Colitis may be fulminant with a rapid downhill clinical course. In addition to the diarrhea, fever, and anemia may be reported. The patient with fulminant colitis has severe abdominal pain and presents a clinical picture similar to that of septicemia, where shock is present. Treatment of colitis depends on the etiology. It may include the elimination of cows-milk protein or other food allergens from the diet, administration of antibiotics and general anti-inflammatory medications such as mesalamine or its derivatives, steroids, or one of a number of other drugs that ameliorate inflammation. The mainstay of therapy for infectious colitis is antimicrobial therapy. A common antibiotic regimen in treatment of patients with colitis is a combination of ceftriaxone and doxycycline. Supportive therapies such as correction of dehydration and anemia, and reducing the intake of carbohydrates, lactose products, soft drinks, and caffeine is often done for most patients with colitis. Irritable bowel syndrome (spastic colitis or spastic colon) has been called colitis, causing confusion despite colitis not being a feature of the disease. Immune mediated colitis is the experimental name in animal studies of ulcerative colitis. It is a synonym of ulcerative colitis, but it should not be used as a synonym when referring to ulcerative colitis.
# Classification
There is no established classification system for colitis. However, it may be classified based on etiology, age and duration of symptom.
## Classification by etiology
## Classification by Anatomy
Colitis may co-exist with inflammation involving other parts of the gastrointestinal tract. It can be classified based on anatomy into:
- Proctitis: When it involves the rectum
- Colitis: When it involves the inflammation is limited to the colon
- Proctocolitis: When it involves the rectum and colon (usually the distal part of the colon 12cm to 15cm above the anus (sigmoid colon)[1][2]
- Enterocolitis: When it involves the small intestine in addition to the colon
### Schematic of Anatomical Classification of Colitis
## Classification by Age
- Infantile (first six months of life)[4][5][6]
- Adult
## Classification by duration of symptoms
- Acute: Less than three months.[7]
- Chronic: Longer than three months. Often months to years.[7]
# Differential Diagnosis
The differential diagnosis of colitis can be classified into two categories according to age group. A work up for colitis must include the following differentials:
## Differential diagnosis in Infants
- Swallowed maternal blood syndrome
- Anorectal fissure
- Necrotizing enterocolitis especially in preterm babies
- Vitamin K dependent hemorrhage
- Other coagulopathies: (hereditary such as coagulation factor deficiency or acquired such as disseminated intravascular coagulopathy)
- Intussusception
- Upper Gastrointestinal Infections
- Enteritis
- Meckel diverticulum
- Intestinal duplication cysts
- Vascular malformations
- Inflammatory bowel disease(early onset)
- Hirschsprung disease complicated by enterocolitis
- Volvulus
- Gastro-duodenal ulcers
- Gastrointestinal duplication cyst
- Liver disease with clotting factor deficiency
- Lymphonodular hyperplasia
## Differential diagnosis in Adults
- Colorectal malignancy
- Crohn's disease
- Behcet's disease
- Arteriovenous malformation
- Diverticulosis
- Enteritis
- Coagulopathy
- Systemic lupus erythematosus(SLE)
- Cytomegalovirus colitis
## Differentiating Between Different Types of Colitis
The symptoms of colitis such as diarrhea especially bloody diarrhea and abdominal pain are seen are seen in all forms of colitis. The table below differentiates among the common causes of colitis:[8][9]
# Causes
## Common Causes
Common causes of proctocolitis include infectious agents such as Chlamydia trachomatis (which causes lymphogranuloma venereum), Neisseria gonorrhoeae, HSV, Shigella dysenteriae and Campylobacter species. It can also be allergic (e.g. food protein-induced proctocolitis), idiopathic (e.g. microscopic colitis), vascular (e.g. ischemic colitis), or autoimmune (e.g. inflammatory bowel disease).
## Causes by Organ System
## Causes in Alphabetical Order
- Aganglionic megacolon
- Albinism [11]
- Alosetron
- Alpha 1-antitrypsin deficiency
- Ampicillin Oral
- Ankylosing spondylitis
- Auranofin
- Autistic enterocolitis
- Azithromycin
- Aztreonam Injection
- Bacillary dysentery
- Bacterial gastroenteritis
- Balantidium coli
- Behcet disease
- Campylobacter jejuni
- Cap polyposis
- Cefaclor
- Cefadroxil
- Cefamandole Nafate Injection
- Cefazolin Sodium Injection
- Cefepime
- Cefepime Injection
- Cefoperazone Sodium Injection
- Cefotaxime Sodium Injection
- Cefotetan Disodium Injection
- Cefoxitin Sodium Injection
- Cefpodoxime
- Ceftazidime
- Ceftazidime Injection
- Ceftizoxime Sodium Injection
- Ceftriaxone Sodium Injection
- Cefuroxime Sodium Injection
- Cephalexin
- Cephalosporin
- Cephradine Oral
- Chemical colitis
- Chlamydia trachomatis
- Cidofovir
- Cilansetron
- Clindamycin
- Clostridium difficile [12]
- Co-amoxiclav
- Colitis ulcerosa
- Collagenous colitis
- Colonic ischemia
- Common variable immunodeficiency
- Corticosteroid
- Crohn's disease
- Cryptosporidiosis
- Cytomegalovirus
- Darifenacin
- Dental braces
- Desogestrel and Ethinyl Estradiol
- Dicloxacillin
- Dirithromycin
- Diversion colitis
- Diverticulosis
- Enoxacin
- Entamoeba histolytica
- Ertapenem
- Erythromycin and Sulfisoxazole
- Escherichia coli O157:H7
- EVAR
- Flucytosine
- Gerson diet
- Giardiasis
- Glycopyrrolate
- Hyoscyamine
- Idelalisib
- Imipenem and Cilastatin Sodium Injection
- Infectious colitis
- Inflammatory bowel disease
- Intestinal ischemia
- Ipilimumab
- Irritable bowel syndrome
- Ischemic colitis
- Isosporiasis
- Ixabepilone
- Lanthanum
- Levofloxacin Oral
- Lincomycin hydrochloride
- Linezolid
- Lomefloxacin
- Loracarbef
- Lymphocytic colitis
- Lysinuric protein intolerance
- Methotrexate
- Miconazole Injection
- Microscopic colitis
- Milk allergy
- Moxifloxacin
- Multiple organ dysfunction syndrome
- Nafcillin Sodium Injection
- Neisseria gonorrhoeae
- Neonatal necrotizing enterocolitis
- Nivolumab
- Norfloxacin
- Ofloxacin injection
- Oxacillin Sodium Injection
- Oxcarbazepine
- Oxybutynin
- Peginterferon alfa-2a
- Penicillin
- Pergolide
- Pigbel
- Piperacillin sodium injection
- Pramipexole
- Prednisolone
- Primary sclerosing cholangitis
- Procyclidine
- Propantheline
- Protein losing enteropathy
- Pseudoephedrine
- Pseudomembranous colitis
- Quinolone
- Radiation colitis
- Radiation proctitis
- Ramosetron
- Reserpine
- Salmonella
- Schistosoma
- Scleroderma
- Sepsis
- Shigella
- Solifenacin
- Solitary rectal ulcer syndrome
- Soy protein
- Sparfloxacin
- Strongyloides stercoralis
- Syphilis
- Tegaserod
- Toxic megacolon
- Treponema pallidum
- Typhlitis
- Ulcerative colitis
- Vasculitis
- Yersinia enterocolitica
## Life Threatening Causes
Example include toxic megacolon, ischemic colitis, infectious colitis such as escherichia coli O157:H7 and shigella.
# Screening
There is insufficient evidence to recommend routine screening of sexual partners of patients with sexually transmitted enteric pathogens.
# Diagnosis
## History and Symptoms
- Symptoms of proctitis include anorectal pain, tenesmus, or rectal discharge.
- Symptoms of proctocolitis include fatigue, weight loss, anorectal pain, tenesmus, rectal discharge, diarrhea or abdominal cramps.
## Laboratory Findings
Laboratory findings consistent with the diagnosis of proctitis include:
- Stool examination: Detection of blood or fecal polymorphonuclear leukocytes using gram-stained smear of any anorectal exudate from anoscopic or anal examination.
- Microbiology workup: NAAT of rectal lesions for HSV, NAAT for Neisseria gonorrhea, syphilis serology, NAAT for Chlamydia trachomatis, and NAAT for Mycoplasma genitalium in case of persistence of symptoms after receiving the recommended treatment. CMV and other opportunistic infections may be evaluated in immunosuppressed individuals as HIV/AIDS.
- An elevated erythrocyte sedimentation rate (ESR) is one typical finding in the acute exacerbation of proctocolitis.
## Other Imaging Findings
### Colonoscopy
Anoscopy or sigmoidoscopy may be helpful in the diagnosis of proctocolitis. Findings on an sigmoidoscopy suggestive of proctocolitis include inflammation of the colonic mucosa extending to 12 cm above the anus and rectal ulcers.
# Treatment
## Medical Therapy
Acute proctocolitis among individuals with receptive anal exposure is often sexually-transmitted. Empiric antibiotic treatment should be started while awaiting for the results of laboratory tests for
patients presenting with anorectal exudate on anoscopy or positive Gram-stained smear of anorectal exudate or secretions polymorphonuclear leukocytes or if anoscopy or Gram stain is not available.[13]
### Recommended Regimen for Acute Proctitis
Ceftriaxone 500 mg IM in a single dose
plus
Doxycycline 100 mg orally 2 times/day for 7 days
- Doxycycline course is continued to 100 mg orally 2 times/day for 21 days in case of perianal or mucosal ulcers, bloody discharge, or tenesmus and a positive rectal chlamydia test.
- For individuals weighing ≥150 kg, 1 g of ceftriaxone is given.
- Patients presenting with mucosal or perianal ulcers or bloody diarrhea with positive NAAT for chlamydia should receive empiric therapy for Lymphogranuloma Venereum (LGV) with a prolonged course of doxycycline 100 mg orally 2 times/day for 3 weeks.[14]
- Patients presenting with painful perianal ulcers or mucosal ulcers on anoscopy should also receive empiric treatment for genital herpes.
- Herpes proctocolitis and LGV occur predominantly among HIV/AIDS patients; hence empiric treatment in those patients should cover genital herpes and LGV.
## Surgery
Surgical intervention is not recommended for the management of proctocolitis.
# Primary Prevention
As proctocolitis can be a sexually transmitted disease, effective measures for the primary prevention of proctocolitis include:
- Counseling on safe sex practices
- Avoiding contact with feces during sexual intercourse
- Hand washing after handing objects or materials that have been in contact with the anal area (i.e., sex toys or barriers) and after touching the anal area.
# Secondary Prevention
Effective measures for the secondary prevention of proctocolitis include:
- Abstinence from sexual activity until the patient and their partners are successfully treated (i.e., completion of a 7-day regimen and resolution of symptoms)
- Sexual partners with individuals treated for chlamydia or gonorrhea <60 days before the onset of symptoms should receive evaluation and empiric treatment of the causative infection
- Testing for other sexually-transmitted diseases
- In case of proctocolitis caused by chlamydia or Neisseria gonorrhea, retesting for the causative organism is recommended 3 months after completion of treatment. | https://www.wikidoc.org/index.php/Amoebic_colitis | |
1980b8e3314fd53e13fc00a8f62fdb60b41b4745 | wikidoc | Antacid | Antacid
# Overview
An antacid is any substance, generally a base, which counteracts stomach acidity. In other words, antacids are stomach acid neutralizers.
# Action mechanism
Antacids perform a neutralization reaction, i.e. they buffer gastric acid, raising the pH to reduce acidity in the stomach. When gastric hydrochloric acid reaches the nerves in the gastrointestinal mucosa, they signal pain to the central nervous system. This happens when these nerves are exposed, as in peptic ulcers. The gastric acid may also reach ulcers in the esophagus or the duodenum.
Other mechanisms may contribute, such as the effect of aluminum ions inhibiting smooth muscle cell contraction and delaying gastric emptying.
# Indications
Antacids are taken by mouth to relieve heartburn, the major symptom of gastroesophageal reflux disease, or acid indigestion. Treatment with antacids alone is symptomatic and only justified for minor symptoms. Peptic ulcers may require H2-receptor antagonists or proton pump inhibitors.
The utility of many combinations of antacids is not clear, although the combination of magnesium and aluminum salts may prevent alteration of bowel habits.
# Side effects
- Aluminum hydroxide: may lead to the formation of insoluble aluminum-phosphate-complexes, with a risk for hypophosphatemia and osteomalacia. Although aluminum has a low gastrointestinal absorption, accumulation may occur in the presence of renal insufficiency. Aluminum-containing drugs may cause constipation.
- Magnesium hydroxide: has laxative properties. Magnesium may accumulate in patients with renal failure leading to hypermagnesemia, with cardiovascular and neurological complications. See Milk of magnesia.
- Carbonate: regular high doses may cause alkalosis, which in turn may result in altered excretion of other drugs, and kidney stones. A chemical reaction between the carbonate and hydrochloric acid may produce carbon dioxide gas. This causes gastric distension which may not be well tolerated.
- Calcium: compounds containing calcium may increase calcium output in the urine, which might be associated to renal stones. Calcium salts may cause Constipation.
- Sodium: increased intake of sodium may be deleterious for arterial hypertension, heart failure and many renal diseases.
# Interactions
Altered pH or complex formation may alter the bioavailability of other drugs, such as tetracycline. Urinary excretion of certain drugs may also be affected.
# Problems with reduced stomach acidity
Reduced stomach acidity may result in an impaired ability to digest and absorb certain nutrients, such as iron and the B vitamins. Since the low pH of the stomach normally kills ingested bacteria, antacids increase the vulnerability to infection. It could also result in reduced bioavailability of some drugs.For example,the bioavailability of ketoconazole(antifungal),is reduced at high intragastric pH.(low acid content).
# Drug names
Examples of antacids (brand names may vary in different countries).
- Aluminum hydroxide (Amphojel®, AlternaGEL®)
- Magnesium hydroxide (Phillips’® Milk of Magnesia)
- Aluminum hydroxide and magnesium hydroxide (Maalox®, Mylanta®)
- Aluminum carbonate gel (Basaljel®)
- Calcium carbonate (Alcalak®, TUMS®, Quick-Eze®, Rennie®, Titralac®, Rolaids®)
- Sodium bicarbonate (Bicarbonate of soda, Alka-Seltzer®)
- Hydrotalcite (Mg6Al2(CO3)(OH)16 · 4(H2O); Talcid®)
- Bismuth subsalicylate (Pepto-Bismol)
- Magaldrate + Simethicone (Pepsil)
ca:Antiàcid
de:Antazidum
hr:Antacidi
nl:Antacidum
sk:Antacidum
sl:Antacid
sr:Антацид
sh:Antacid
fi:Antasidi
sv:Antacida
th:ยาลดกรด | Antacid
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
An antacid is any substance, generally a base, which counteracts stomach acidity. In other words, antacids are stomach acid neutralizers.
# Action mechanism
Antacids perform a neutralization reaction, i.e. they buffer gastric acid, raising the pH to reduce acidity in the stomach. When gastric hydrochloric acid reaches the nerves in the gastrointestinal mucosa, they signal pain to the central nervous system. This happens when these nerves are exposed, as in peptic ulcers. The gastric acid may also reach ulcers in the esophagus or the duodenum.
Other mechanisms may contribute, such as the effect of aluminum ions inhibiting smooth muscle cell contraction and delaying gastric emptying.
# Indications
Antacids are taken by mouth to relieve heartburn, the major symptom of gastroesophageal reflux disease, or acid indigestion. Treatment with antacids alone is symptomatic and only justified for minor symptoms. Peptic ulcers may require H2-receptor antagonists or proton pump inhibitors.
The utility of many combinations of antacids is not clear, although the combination of magnesium and aluminum salts may prevent alteration of bowel habits.
# Side effects
- Aluminum hydroxide: may lead to the formation of insoluble aluminum-phosphate-complexes, with a risk for hypophosphatemia and osteomalacia. Although aluminum has a low gastrointestinal absorption, accumulation may occur in the presence of renal insufficiency. Aluminum-containing drugs may cause constipation.
- Magnesium hydroxide: has laxative properties. Magnesium may accumulate in patients with renal failure leading to hypermagnesemia, with cardiovascular and neurological complications. See Milk of magnesia.
- Carbonate: regular high doses may cause alkalosis, which in turn may result in altered excretion of other drugs, and kidney stones. A chemical reaction between the carbonate and hydrochloric acid may produce carbon dioxide gas. This causes gastric distension which may not be well tolerated.
- Calcium: compounds containing calcium may increase calcium output in the urine, which might be associated to renal stones. Calcium salts may cause Constipation.
- Sodium: increased intake of sodium may be deleterious for arterial hypertension, heart failure and many renal diseases.
# Interactions
Altered pH or complex formation may alter the bioavailability of other drugs, such as tetracycline. Urinary excretion of certain drugs may also be affected.
# Problems with reduced stomach acidity
Reduced stomach acidity may result in an impaired ability to digest and absorb certain nutrients, such as iron and the B vitamins. Since the low pH of the stomach normally kills ingested bacteria, antacids increase the vulnerability to infection. It could also result in reduced bioavailability of some drugs.For example,the bioavailability of ketoconazole(antifungal),is reduced at high intragastric pH.(low acid content).
# Drug names
Examples of antacids (brand names may vary in different countries).
- Aluminum hydroxide (Amphojel®, AlternaGEL®)
- Magnesium hydroxide (Phillips’® Milk of Magnesia)
- Aluminum hydroxide and magnesium hydroxide (Maalox®, Mylanta®)
- Aluminum carbonate gel (Basaljel®)
- Calcium carbonate (Alcalak®, TUMS®, Quick-Eze®, Rennie®, Titralac®, Rolaids®)
- Sodium bicarbonate (Bicarbonate of soda, Alka-Seltzer®)
- Hydrotalcite (Mg6Al2(CO3)(OH)16 · 4(H2O); Talcid®)
- Bismuth subsalicylate (Pepto-Bismol)
- Magaldrate + Simethicone (Pepsil)
Template:Major Drug Groups
Template:Antacids
Template:WikiDoc Sources
ca:Antiàcid
de:Antazidum
hr:Antacidi
nl:Antacidum
sk:Antacidum
sl:Antacid
sr:Антацид
sh:Antacid
fi:Antasidi
sv:Antacida
th:ยาลดกรด | https://www.wikidoc.org/index.php/Amphojel | |
63a92174ab6044c1c46693eaef48ab1eccd6b3eb | wikidoc | Ampoule | Ampoule
An ampoule (also ampule) is a small glass sealed vial which is used to contain or preserve a fluid.
# Historically
Historically ampoules were used to contain a small sample of a person's blood after death, which was entombed alongside them in many Christian catacombs. It was originally believed that only martyrs were given this burial treatment, but many believe that it was a widely-practised tradition.
# Famous Ampoules
In Naples, a centuries-old ritual takes place every year on the 19th of September: the Blood Miracle of San Gennaro. An ampoule, dating back to the year 305, filled with the blood of Saint Gennaro, bishop of Benevento, is placed next to his bust in the Naples Cathedral. After intense prayers by the parenti di San Geranno, the blood in the ampoule liquifies. The earliest records of this phenomenon date back to 313.
# Modern usage
Modern ampoules are most commonly used to contain pharmaceutical hypodermic solutions or high purity chemicals that must be protected from air. They are hermetically sealed by melting the thin top with an open flame, and are designed with a (1) scoring around the neck (2) break ring around the neck or (3) a small cut on the neck. When pressure is applied, the top will break off and the medicine can be reached.
After opening the ampoule, the solution is filtered to remove any glass fragments which may have fallen in the solution when the ampoule was opened.
- Pharmaceutical ampoules
- Pharmaceutical ampoules
- A collection of ancient ampoules
# Production
Ampoules are produced from tubing glass. Tubes are inserted in a carrousel and heat is applied. By applying the right amount of heat and using gravity the shape of the ampoule is achieved. As many parameters will influence the production process vision systems are introduced in the carrousel and on the end of the production line.
de:Ampulle (Behälter)
he:אמפולה
nl:Ampul (medisch) | Ampoule
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
An ampoule (also ampule) is a small glass sealed vial which is used to contain or preserve a fluid.
# Historically
Historically ampoules were used to contain a small sample of a person's blood after death, which was entombed alongside them in many Christian catacombs. It was originally believed that only martyrs were given this burial treatment, but many believe that it was a widely-practised tradition.
# Famous Ampoules
In Naples, a centuries-old ritual takes place every year on the 19th of September: the Blood Miracle of San Gennaro. An ampoule, dating back to the year 305, filled with the blood of Saint Gennaro, bishop of Benevento, is placed next to his bust in the Naples Cathedral. After intense prayers by the parenti di San Geranno, the blood in the ampoule liquifies. The earliest records of this phenomenon date back to 313.
# Modern usage
Modern ampoules are most commonly used to contain pharmaceutical hypodermic solutions or high purity chemicals that must be protected from air. They are hermetically sealed by melting the thin top with an open flame, and are designed with a (1) scoring around the neck (2) break ring around the neck or (3) a small cut on the neck. When pressure is applied, the top will break off and the medicine can be reached.
After opening the ampoule, the solution is filtered to remove any glass fragments which may have fallen in the solution when the ampoule was opened.
- Pharmaceutical ampoules
- Pharmaceutical ampoules
- A collection of ancient ampoules
# Production
Ampoules are produced from tubing glass. Tubes are inserted in a carrousel and heat is applied. By applying the right amount of heat and using gravity the shape of the ampoule is achieved. As many parameters will influence the production process vision systems are introduced in the carrousel and on the end of the production line.
de:Ampulle (Behälter)
he:אמפולה
nl:Ampul (medisch)
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Ampoule | |
71503b144466bd9fd6add12f43143f597290377d | wikidoc | Amylase | Amylase
# Overview
- Amylase is an enzyme that splits polysaccharides
- Serum reference range: 60-180 U/l
Amylase is the name given to glycoside hydrolase enzymes that break down starch into maltose molecules. Although the amylases are designated by different Greek letters, they all act on α-1,4-glycosidic bonds. Under the original name of diastase, amylase was the first enzyme to be found and isolated (by Anselme Payen in 1833).
# Classification
## α-Amylase
(EC 3.2.1.1 ) (CAS# 9014-71-5) (alternate names: 1,4-α-D-glucan glucanohydrolase; glycogenase)
The α-amylases are calcium metalloenzymes, completely unable to function in the absence of calcium. By acting at random locations along the starch chain, α-amylase breaks down long-chain carbohydrates, ultimately yielding maltotriose and maltose from amylose, or maltose, glucose and "limit dextrin" from amylopectin. Because it can act anywhere on the substrate, α-amylase tends to be faster-acting than β-amylase. In animals, it is a major digestive enzyme.
In human physiology, both the salivary and pancreatic amylases are α-Amylases. They are discussed in much more detail at alpha-Amylase.
## β-Amylase
(EC 3.2.1.2 ) (alternate names: 1,4-α-D-glucan maltohydrolase; glycogenase; saccharogen amylase)
Another form of amylase, β-amylase is also synthesized by bacteria, fungi, and plants. Working from the non-reducing end, β-amylase catalyzes the hydrolysis of the second α-1,4 glycosidic bond, cleaving off two glucose units (maltose) at a time. During the ripening of fruit, β-amylase breaks starch into sugar, resulting in the sweet flavor of ripe fruit. Both are present in seeds; β-amylase is present prior to germination, whereas α-amylase and proteases appear once germination has begun. Cereal grain amylase is key to the production of malt. Many microbes also produce amylase to degrade extracellular starches. Animal tissues do not contain β-amylase, although it may be present in microrganisms contained within the digestive tract.
## γ-Amylase
(EC 3.2.1.3 ) (alternative names: Glucan 1,4-α-glucosidase; amyloglucosidase; Exo-1,4-α-glucosidase; glucoamylase; lysosomal α-glucosidase; 1,4-α-D-glucan glucohydrolase)
In addition to cleaving the last α(1-4)glycosidic linkages at the nonreducing end of amylose and amylopectin, yielding glucose, γ-amylase will cleave α(1-6) glycosidic linkages.
# Uses
Amylase enzymes are used extensively in bread making to break down complex sugars such as starch (found in flour) into simple sugars. Yeast then feeds on these simple sugars and converts it into the waste products of alcohol and CO2. This imparts flavour and causes the bread to rise. While Amylase enzymes are found naturally in yeast cells, it takes time for the yeast to produce enough of these enzymes to break down significant quantities of starch in the bread. This is the reason for long fermented doughs such as sour dough. Modern bread making techniques have included amylase enzymes into bread improver thereby making the bread making process faster and more practical for commercial use.
Bacilliary amylase is also used in detergents to dissolve starches from fabrics.
Workers in factories that work with amylase for any of the above uses are at increased risk of occupational asthma. 5-9% of bakers have a positive skin test, and a fourth to a third of bakers with breathing problems are hypersensitive to amylase.
An inhibitor of alpha-amylase called phaseolamin has been tested as a potential diet aid.
# Differential Diagnosis of Abnormalities in Amylase
## Increased Amylase
- Acute cholecystitis
- Acute pancreatitis
- After endoscopic retrograde cholangio-pancreatography (ECRP)
- Appendicitis
- Ascites
- Bronchial Cancer
- Diabetic Ketoacidosis
- Drugs:
Indinavir
- Indinavir
- Zinc Acetate
- Esophageal Cancer
- Intestinal infarction
- Intestinal obstruction
- Macroamylasemia
- Malignancies
- Ovarian Cancer
- Pancreas abscess
- Pancreas pseudocyst
- Pancreatic neoplasm
- Parotitis
- Penetrating, perforated peptic ulcer
- Peritonitis
- Pulmonary infarction
- Renal failure
- Ruptured ectopic pregnancy | Amylase
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
- Amylase is an enzyme that splits polysaccharides
- Serum reference range: 60-180 U/l
Amylase is the name given to glycoside hydrolase enzymes that break down starch into maltose molecules. Although the amylases are designated by different Greek letters, they all act on α-1,4-glycosidic bonds. Under the original name of diastase, amylase was the first enzyme to be found and isolated (by Anselme Payen in 1833).
# Classification
## α-Amylase
(EC 3.2.1.1 ) (CAS# 9014-71-5) (alternate names: 1,4-α-D-glucan glucanohydrolase; glycogenase)
The α-amylases are calcium metalloenzymes, completely unable to function in the absence of calcium. By acting at random locations along the starch chain, α-amylase breaks down long-chain carbohydrates, ultimately yielding maltotriose and maltose from amylose, or maltose, glucose and "limit dextrin" from amylopectin. Because it can act anywhere on the substrate, α-amylase tends to be faster-acting than β-amylase. In animals, it is a major digestive enzyme.
In human physiology, both the salivary and pancreatic amylases are α-Amylases. They are discussed in much more detail at alpha-Amylase.
## β-Amylase
(EC 3.2.1.2 ) (alternate names: 1,4-α-D-glucan maltohydrolase; glycogenase; saccharogen amylase)
Another form of amylase, β-amylase is also synthesized by bacteria, fungi, and plants. Working from the non-reducing end, β-amylase catalyzes the hydrolysis of the second α-1,4 glycosidic bond, cleaving off two glucose units (maltose) at a time. During the ripening of fruit, β-amylase breaks starch into sugar, resulting in the sweet flavor of ripe fruit. Both are present in seeds; β-amylase is present prior to germination, whereas α-amylase and proteases appear once germination has begun. Cereal grain amylase is key to the production of malt. Many microbes also produce amylase to degrade extracellular starches. Animal tissues do not contain β-amylase, although it may be present in microrganisms contained within the digestive tract.
## γ-Amylase
(EC 3.2.1.3 ) (alternative names: Glucan 1,4-α-glucosidase; amyloglucosidase; Exo-1,4-α-glucosidase; glucoamylase; lysosomal α-glucosidase; 1,4-α-D-glucan glucohydrolase)
In addition to cleaving the last α(1-4)glycosidic linkages at the nonreducing end of amylose and amylopectin, yielding glucose, γ-amylase will cleave α(1-6) glycosidic linkages.
# Uses
Amylase enzymes are used extensively in bread making to break down complex sugars such as starch (found in flour) into simple sugars. Yeast then feeds on these simple sugars and converts it into the waste products of alcohol and CO2. This imparts flavour and causes the bread to rise. While Amylase enzymes are found naturally in yeast cells, it takes time for the yeast to produce enough of these enzymes to break down significant quantities of starch in the bread. This is the reason for long fermented doughs such as sour dough. Modern bread making techniques have included amylase enzymes into bread improver thereby making the bread making process faster and more practical for commercial use.
Bacilliary amylase is also used in detergents to dissolve starches from fabrics.
Workers in factories that work with amylase for any of the above uses are at increased risk of occupational asthma. 5-9% of bakers have a positive skin test, and a fourth to a third of bakers with breathing problems are hypersensitive to amylase. [1]
An inhibitor of alpha-amylase called phaseolamin has been tested as a potential diet aid. [2]
# Differential Diagnosis of Abnormalities in Amylase
## Increased Amylase
- Acute cholecystitis
- Acute pancreatitis
- After endoscopic retrograde cholangio-pancreatography (ECRP)
- Appendicitis
- Ascites
- Bronchial Cancer
- Diabetic Ketoacidosis
- Drugs:
Indinavir
- Indinavir
- Zinc Acetate
- Esophageal Cancer
- Intestinal infarction
- Intestinal obstruction
- Macroamylasemia
- Malignancies
- Ovarian Cancer
- Pancreas abscess
- Pancreas pseudocyst
- Pancreatic neoplasm
- Parotitis
- Penetrating, perforated peptic ulcer
- Peritonitis
- Pulmonary infarction
- Renal failure
- Ruptured ectopic pregnancy | https://www.wikidoc.org/index.php/Amylase | |
a2b8989c426ac5f26b478c4d56c7c207f21c8415 | wikidoc | Amyloid | Amyloid
# Overview
Amyloids are insoluble fibrous protein aggregations sharing specific structural traits.
# Definition Controversy
- The name amyloid comes from the early mistaken identification of the substance "starch" (amylum in Latin), based on crude iodine-staining techniques. For a period, the scientific community debated whether or not amyloid deposits were fatty deposits or carbohydrate deposits until it was finally resolved that it was neither, but rather a deposition of proteinaceous mass.
- The classical, histopathological definition of amyloid is an extracellular, proteinaceous deposit exhibiting cross-beta structure. This is due to misfolding of unstable proteins. Common to most cross-beta type structures, they are generally identified by apple-green birefringence when stained with Congo Red and seen under polarized light. These deposits often recruit various sugars and other components such as Serum Amyloid P component, resulting in complex, and sometimes heterogeneous structures.
- Recently, this definition has come into question as some classic amyloid species have been observed in distinctly intracellular locations.
- A more recent, biophysical definition is broader, including any polypeptide which adopts a cross-beta polymerization, in vivo, or in vitro. Some of these, although demonstrably cross-beta sheet, fail other characteristic tests of amyloid, such as the Congo Red birefringence test. Microbiologists and biophysicists have largely adopted this definition, leading to some conflict in the biological community over the issue of language.
# Diseases Featuring Amyloids
- Amyloidosis
- Medulary Carcinoma of the Thyroid
- Alzheimer's disease
- Transmissible spongiform encephalopathy
- Yeast Prions Rnq1
- Sporadic Inclusion Body Myositis (S-IBM)
# Non-Disease Amyloids
(Mostly using the biophysical definition)
- Native amyloids in organisms:
Curli E. coli Protein (curlin)
Podospora Anserina Prion Het-s
Malarial coat protein
Spider silk (not all spiders)
Mammalian melanosomes (pMel)
Tissue-type plasminogen activator (tPA)
- Curli E. coli Protein (curlin)
- Podospora Anserina Prion Het-s
- Malarial coat protein
- Spider silk (not all spiders)
- Mammalian melanosomes (pMel)
- Tissue-type plasminogen activator (tPA)
- Proteins and peptides known to make amyloid without any known disease
Calcitonin
- Calcitonin
- Proteins and peptides engineered to make amyloid
# Amyloid Biophysics
- Amyloid is characterized by a cross-beta sheet quaternary structure; that is, the strands come from different monomers and align perpendicular to the axis of the fibril. While amyloid is usually identified using fluorescent dyes, stain polarimetry, circular dichroism, or FTIR (all indirect measurements), the gold standard test to see if a structure contains cross-beta fibers is by placing a sample in an x-ray diffraction beam; there are two characteristic scattering diffraction signals produced at 4.7 and 10 Ångstroms (0.47 nm and 1.0 nm), corresponding to the interstrand and stacking distances in beta sheets. It should be noted that the "stacks" of beta sheet are short and traverse the breadth of the amyloid fibril; the length of the amyloid fibril is built by aligned strands.
- Amyloid polymerization is generally sequence-sensitive, that is, causing mutations in the sequence can prevent self-assembly, especially if the mutation is a beta-sheet breaker, such as proline. For example, humans produce an amyloidogenic peptide associated with type II diabetes, but, in Rodentia, a proline is substituted in a critical location and amyloidogenesis does not occur.
- There are two broad classes of amyloid-forming polypeptide sequences. Glutamine-rich polypeptides are important in the amyloidogenesis of yeast and mammalian prions, as well as Huntington's disease. When peptides are in a beta-sheet conformation, particularly when the residues are parallel and in-register (causing alignment), glutamines can brace the structure by forming intrastrand hydrogen bonding between its amide carbonyls and nitrogens. In general, for this class of diseases, toxicity correlates with glutamine content. This has been observed in studies of onset age for Huntington's disease (the longer the polyglutamine sequence, the sooner the symptoms appear), and has been confirmed in a C. elegans model system with engineered polyglutamine peptides.
- Other polypeptides and proteins, such as amylin and the Alzheimer's beta protein do not have a simple consensus sequence and are thought to operate by hydrophobic association. Among the hydrophobic residues, aromatic amino acids are found to have the highest amyloidogenic propensity.
- For these peptides, cross-polymerization (fibrils of one polypeptide sequence causing other fibrils of another sequence to form) is a phenomenon observed in vitro. This phenomenon is important since it would explain interspecies prion propagation and amyloid biophysics differential rates of propagation, as well as a statistical link between Alzheimer's and diabetes. In general, cross-polymerization is more efficient the more similar the peptide sequence, though entirely dissimilar sequences can cross-polymerize and highly similar sequences can even be "blockers" which prevent polymerization. Polypeptides will not cross-polymerize their mirror-image counterparts, indicating that the phenomenon involves specific binding and recognition events.
- Xu, using atomic force microscopy, has shown in both lysozyme and human tau40, the formation of amyloid fibers is a two-step process in which proteins first aggregate into uniform colloidal spheres of ~20nm diameter. The spheres then join to form characteristic linear chains, which evolve over time into mature amyloid fibers. He proposes that aggregation drives conformational change and that a conformational change is not essential to initiate the aggregation process.
# Amyloid Pathology
- The reasons for amyloid association with disease is unclear. In many cases, the deposits physically disrupt tissue architecture, suggesting disruption of function by some bulk process.
- In other cases, cell death is believed to precede amyloid deposition, suggesting that small amyloid-like oligomers (possibly but not necessarily biophysically amyloid) cause cell death. There is significant speculation that amyloid fibrils can also puncture cells or cause problems such as ionic imbalance in cells.
- Further speculation has led to the hypothesis that while amyloid association may be the cause of health issues, the association itself is initiated by an underlying problem, such as one/some of the above mentioned side effects like calcium ion concentration imbalances.
- For more information on the deposition of amyloid protein in the body (amyloidosis), click here.
# Histological Staining
- Amyloid is typically identified by a change in the fluorescence intensity of planar aromatic dyes such as Thioflavin T or Congo Red. Congo Red postitivity remains the gold standard for diagnosis of amyloidosis.
- This is generally attributed to the environmental change, as these dyes intercalate between beta-strands.
- Congophillic amyloid plaques generally cause apple-green birefringence, when viewed through crossed polarimetric filters.
- To avoid nonspecific staining, histology stains, such as haematoxylin and eosin stain, are used to quench the dyes' activity in other places where the dye might bind, such as the nucleus. The dawn of antibody technology and immunohistochemistry has made specific staining easier, but this can often cause trouble because epitopes can be concealed in the amyloid fold; an amyloid protein structure is generally a different conformation from that which the antibody recognizes. | Amyloid
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Amyloids are insoluble fibrous protein aggregations sharing specific structural traits.
# Definition Controversy
- The name amyloid comes from the early mistaken identification of the substance "starch" (amylum in Latin), based on crude iodine-staining techniques. For a period, the scientific community debated whether or not amyloid deposits were fatty deposits or carbohydrate deposits until it was finally resolved that it was neither, but rather a deposition of proteinaceous mass.[1]
- The classical, histopathological definition of amyloid is an extracellular, proteinaceous deposit exhibiting cross-beta structure. This is due to misfolding of unstable proteins. Common to most cross-beta type structures, they are generally identified by apple-green birefringence when stained with Congo Red and seen under polarized light. These deposits often recruit various sugars and other components such as Serum Amyloid P component, resulting in complex, and sometimes heterogeneous structures.[2]
- Recently, this definition has come into question as some classic amyloid species have been observed in distinctly intracellular locations.
- A more recent, biophysical definition is broader, including any polypeptide which adopts a cross-beta polymerization, in vivo, or in vitro. Some of these, although demonstrably cross-beta sheet, fail other characteristic tests of amyloid, such as the Congo Red birefringence test. Microbiologists and biophysicists have largely adopted this definition, leading to some conflict in the biological community over the issue of language.
# Diseases Featuring Amyloids
- Amyloidosis
- Medulary Carcinoma of the Thyroid
- Alzheimer's disease
- Transmissible spongiform encephalopathy
- Yeast Prions [Sup35] [3] Rnq1
- Sporadic Inclusion Body Myositis (S-IBM)
# Non-Disease Amyloids
(Mostly using the biophysical definition)
- Native amyloids in organisms:
Curli E. coli Protein (curlin)
Podospora Anserina Prion Het-s
Malarial coat protein
Spider silk (not all spiders)
Mammalian melanosomes (pMel)
Tissue-type plasminogen activator (tPA)
- Curli E. coli Protein (curlin)
- Podospora Anserina Prion Het-s
- Malarial coat protein
- Spider silk (not all spiders)
- Mammalian melanosomes (pMel)
- Tissue-type plasminogen activator (tPA)
- Proteins and peptides known to make amyloid without any known disease
Calcitonin
- Calcitonin
- Proteins and peptides engineered to make amyloid
# Amyloid Biophysics
- Amyloid is characterized by a cross-beta sheet quaternary structure; that is, the strands come from different monomers and align perpendicular to the axis of the fibril. While amyloid is usually identified using fluorescent dyes, stain polarimetry, circular dichroism, or FTIR (all indirect measurements), the gold standard test to see if a structure contains cross-beta fibers is by placing a sample in an x-ray diffraction beam; there are two characteristic scattering diffraction signals produced at 4.7 and 10 Ångstroms (0.47 nm and 1.0 nm), corresponding to the interstrand and stacking distances in beta sheets. It should be noted that the "stacks" of beta sheet are short and traverse the breadth of the amyloid fibril; the length of the amyloid fibril is built by aligned strands.
- Amyloid polymerization is generally sequence-sensitive, that is, causing mutations in the sequence can prevent self-assembly, especially if the mutation is a beta-sheet breaker, such as proline. For example, humans produce an amyloidogenic peptide associated with type II diabetes, but, in Rodentia, a proline is substituted in a critical location and amyloidogenesis does not occur.
- There are two broad classes of amyloid-forming polypeptide sequences. Glutamine-rich polypeptides are important in the amyloidogenesis of yeast and mammalian prions, as well as Huntington's disease. When peptides are in a beta-sheet conformation, particularly when the residues are parallel and in-register (causing alignment), glutamines can brace the structure by forming intrastrand hydrogen bonding between its amide carbonyls and nitrogens. In general, for this class of diseases, toxicity correlates with glutamine content. This has been observed in studies of onset age for Huntington's disease (the longer the polyglutamine sequence, the sooner the symptoms appear), and has been confirmed in a C. elegans model system with engineered polyglutamine peptides.
- Other polypeptides and proteins, such as amylin and the Alzheimer's beta protein do not have a simple consensus sequence and are thought to operate by hydrophobic association. Among the hydrophobic residues, aromatic amino acids are found to have the highest amyloidogenic propensity.
- For these peptides, cross-polymerization (fibrils of one polypeptide sequence causing other fibrils of another sequence to form) is a phenomenon observed in vitro. This phenomenon is important since it would explain interspecies prion propagation and amyloid biophysics differential rates of propagation, as well as a statistical link between Alzheimer's and diabetes. In general, cross-polymerization is more efficient the more similar the peptide sequence, though entirely dissimilar sequences can cross-polymerize and highly similar sequences can even be "blockers" which prevent polymerization. Polypeptides will not cross-polymerize their mirror-image counterparts, indicating that the phenomenon involves specific binding and recognition events.
- Xu, using atomic force microscopy, has shown in both lysozyme and human tau40, the formation of amyloid fibers is a two-step process in which proteins first aggregate into uniform colloidal spheres of ~20nm diameter. The spheres then join to form characteristic linear chains, which evolve over time into mature amyloid fibers. He proposes that aggregation drives conformational change and that a conformational change is not essential to initiate the aggregation process.[4]
# Amyloid Pathology
- The reasons for amyloid association with disease is unclear. In many cases, the deposits physically disrupt tissue architecture, suggesting disruption of function by some bulk process.
- In other cases, cell death is believed to precede amyloid deposition, suggesting that small amyloid-like oligomers (possibly but not necessarily biophysically amyloid) cause cell death. There is significant speculation that amyloid fibrils can also puncture cells or cause problems such as ionic imbalance in cells.
- Further speculation has led to the hypothesis that while amyloid association may be the cause of health issues, the association itself is initiated by an underlying problem, such as one/some of the above mentioned side effects like calcium ion concentration imbalances.
- For more information on the deposition of amyloid protein in the body (amyloidosis), click here.
# Histological Staining
- Amyloid is typically identified by a change in the fluorescence intensity of planar aromatic dyes such as Thioflavin T or Congo Red. Congo Red postitivity remains the gold standard for diagnosis of amyloidosis.
- This is generally attributed to the environmental change, as these dyes intercalate between beta-strands.
- Congophillic amyloid plaques generally cause apple-green birefringence, when viewed through crossed polarimetric filters.
- To avoid nonspecific staining, histology stains, such as haematoxylin and eosin stain, are used to quench the dyes' activity in other places where the dye might bind, such as the nucleus. The dawn of antibody technology and immunohistochemistry has made specific staining easier, but this can often cause trouble because epitopes can be concealed in the amyloid fold; an amyloid protein structure is generally a different conformation from that which the antibody recognizes. | https://www.wikidoc.org/index.php/Amyloid | |
95848254131442134d029cb49a2751ec2cc966f9 | wikidoc | Amylose | Amylose
Amylose (CAS# 9005-82-7) is a planar polymer of glucose linked mainly by α(1→4) bonds. It can be made of several thousand glucose units. It is one of the two components of starch, the other being amylopectin.
The α(1→4) bonds promote the formation of a helix structure. The structural formula of amylose is pictured at right. The number of repeated glucose subunits (n) can be many thousands (usually in the range of 300 to 3000).
Amylose starch is less readily digested than amylopectin; however, it takes up less space so is preferred for storage in plants: it makes-up about 30% of the stored starch in plants. The digestive enzyme amylase works on the ends of the starch molecule, breaking it down into sugars.
Iodine molecules fit neatly inside the helical structure of amylose, binding with the starch polymer that absorbs certain known wavelengths of light. Hence, a common test for starch is to mix it with a small amount of yellow iodine solution. In the presence of amylose, a blue-black color will be observed. The intensity of the color can be tested with a colorimeter, using a red filter to discern the concentration of starch present in the solution.
High-amylose varieties of rice have a much lower glycemic load, which could be beneficial for diabetics. | Amylose
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Amylose (CAS# 9005-82-7) is a planar polymer of glucose linked mainly by α(1→4) bonds. It can be made of several thousand glucose units. It is one of the two components of starch, the other being amylopectin.
The α(1→4) bonds promote the formation of a helix structure. The structural formula of amylose is pictured at right. The number of repeated glucose subunits (n) can be many thousands (usually in the range of 300 to 3000).
Amylose starch is less readily digested than amylopectin; however, it takes up less space so is preferred for storage in plants: it makes-up about 30% of the stored starch in plants. The digestive enzyme amylase works on the ends of the starch molecule, breaking it down into sugars.
Iodine molecules fit neatly inside the helical structure of amylose, binding with the starch polymer that absorbs certain known wavelengths of light. Hence, a common test for starch is to mix it with a small amount of yellow iodine solution. In the presence of amylose, a blue-black color will be observed. The intensity of the color can be tested with a colorimeter, using a red filter to discern the concentration of starch present in the solution.
High-amylose varieties of rice have a much lower glycemic load, which could be beneficial for diabetics.
# External links
- glycemic load
Template:Carbs
da:Amylose
de:Amylose
eo:Amilozo
it:Amilosio
he:עמילוז
ms:Amilosa
nl:Amylose
no:Amylose
sv:Amylos
uk:Амілоза
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Amylose | |
263843b6a18bb7ef1db506d979b7cfd4ebb0184f | wikidoc | Anatomy | Anatomy
Anatomy (from the Greek Template:Polytonic anatomia, from Template:Polytonic ana: separate, apart from, and temnein, to cut up, cut open) is a branch of biology that is the consideration of the structure of living things. It is a general term that includes human anatomy, animal anatomy (zootomy) and plant anatomy (phytotomy). In some of its facets anatomy is closely related to embryology, comparative anatomy and comparative embryology, through common roots in evolution.
Anatomy is subdivided into gross anatomy (or macroscopic anatomy) and microscopic anatomy. Gross anatomy (also called topographical anatomy, regional anatomy, or anthropotomy) is the study of anatomical structures that can be seen by unaided vision. Microscopic anatomy is the study of minute anatomical structures assisted with microscopes, which includes histology (the study of the organisation of tissues), and cytology (the study of cells).
The history of anatomy has been characterized, over time, by a continually developing understanding of the functions of organs and structures in the body. Methods have also advanced dramatically, advancing from examination of animals through dissection of cadavers (dead human bodies) to technologically complex techniques developed in the 20th century.
Anatomy should not be confused with anatomical pathology (also called morbid anatomy or histopathology), which is the study of the gross and microscopic appearances of diseased organs.
# Superficial anatomy
Superficial anatomy or surface anatomy is important in anatomy being the study of anatomical landmarks that can be readily seen from the contours or the surface of the body. With knowledge of superficial anatomy, physicians or veterinary surgeons gauge the position and anatomy of the associated deeper structures.
# Human anatomy
Human anatomy, including gross human anatomy and histology, is primarily the scientific study of the morphology of the adult human body.
Generally, students of certain biological sciences, paramedics, physiotherapists, nurses and medical students learn gross anatomy and microscopic anatomy from anatomical models, skeletons, textbooks, diagrams, photographs, lectures and tutorials. The study of microscopic anatomy (or histology) can be aided by practical experience examining histological preparations (or slides) under a microscope; and in addition, medical students generally also learn gross anatomy with practical experience of dissection and inspection of cadavers (dead human bodies).
Human anatomy, physiology and biochemistry are complementary basic medical sciences, which are generally taught to medical students in their first year at medical school. Human anatomy can be taught regionally or systemically; that is, respectively, studying anatomy by bodily regions such as the head and chest, or studying by specific systems, such as the nervous or respiratory systems. The major anatomy textbook, Gray's Anatomy, has recently been reorganized from a systems format to a regional format, in line with modern teaching methods. A thorough working knowledge of anatomy is required by all medical doctors, especially surgeons, and doctors working in some diagnostic specialities, such as histopathology and radiology.
Academic human anatomists are usually employed by universities, medical schools or teaching hospitals. They are often involved in teaching anatomy, and research into certain systems, organs, tissues or cells.
# Other branches
Comparative anatomy relates to the comparison of anatomical structures (both gross and microscopic) in different animals.
Anthropological anatomy or physical anthropology relates to the comparison of the anatomy of different races of humans.
Artistic anatomy relates to anatomic studies for artistic reasons. | Anatomy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Template:Editor help
Anatomy (from the Greek Template:Polytonic anatomia, from Template:Polytonic ana: separate, apart from, and temnein, to cut up, cut open) is a branch of biology that is the consideration of the structure of living things. It is a general term that includes human anatomy, animal anatomy (zootomy) and plant anatomy (phytotomy). In some of its facets anatomy is closely related to embryology, comparative anatomy and comparative embryology,[1] through common roots in evolution.
Anatomy is subdivided into gross anatomy (or macroscopic anatomy) and microscopic anatomy.[1] Gross anatomy (also called topographical anatomy, regional anatomy, or anthropotomy) is the study of anatomical structures that can be seen by unaided vision.[1] Microscopic anatomy is the study of minute anatomical structures assisted with microscopes, which includes histology (the study of the organisation of tissues),[1] and cytology (the study of cells).
The history of anatomy has been characterized, over time, by a continually developing understanding of the functions of organs and structures in the body. Methods have also advanced dramatically, advancing from examination of animals through dissection of cadavers (dead human bodies) to technologically complex techniques developed in the 20th century.
Anatomy should not be confused with anatomical pathology (also called morbid anatomy or histopathology), which is the study of the gross and microscopic appearances of diseased organs.
# Superficial anatomy
Superficial anatomy or surface anatomy is important in anatomy being the study of anatomical landmarks that can be readily seen from the contours or the surface of the body.[1] With knowledge of superficial anatomy, physicians or veterinary surgeons gauge the position and anatomy of the associated deeper structures.
# Human anatomy
Human anatomy, including gross human anatomy and histology, is primarily the scientific study of the morphology of the adult human body.[1]
Generally, students of certain biological sciences, paramedics, physiotherapists, nurses and medical students learn gross anatomy and microscopic anatomy from anatomical models, skeletons, textbooks, diagrams, photographs, lectures and tutorials. The study of microscopic anatomy (or histology) can be aided by practical experience examining histological preparations (or slides) under a microscope; and in addition, medical students generally also learn gross anatomy with practical experience of dissection and inspection of cadavers (dead human bodies).
Human anatomy, physiology and biochemistry are complementary basic medical sciences, which are generally taught to medical students in their first year at medical school. Human anatomy can be taught regionally or systemically;[1] that is, respectively, studying anatomy by bodily regions such as the head and chest, or studying by specific systems, such as the nervous or respiratory systems. The major anatomy textbook, Gray's Anatomy, has recently been reorganized from a systems format to a regional format,[2][3] in line with modern teaching methods. A thorough working knowledge of anatomy is required by all medical doctors, especially surgeons, and doctors working in some diagnostic specialities, such as histopathology and radiology.
Academic human anatomists are usually employed by universities, medical schools or teaching hospitals. They are often involved in teaching anatomy, and research into certain systems, organs, tissues or cells.
# Other branches
Comparative anatomy relates to the comparison of anatomical structures (both gross and microscopic) in different animals.[1]
Anthropological anatomy or physical anthropology relates to the comparison of the anatomy of different races of humans.
Artistic anatomy relates to anatomic studies for artistic reasons. | https://www.wikidoc.org/index.php/Anatomic | |
5c732af5c5b147e8ee228dfa619922f303f8de6a | wikidoc | Aniline | Aniline
# Overview
Aniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. It is the simplest and one of the most imporant aromatic amines, being used as a precursor to more complex chemicals. Its main application is in the manufacture of polyurethane. Like most volatile amines, it possesses a somewhat unpleasant odour of rotten fish and also has a burning aromatic taste; it is a highly acrid poison. It ignites readily, burning with a smoky flame.
# Structure and synthesis
Consisting of a phenyl group attached to an amino group, aniline is produced industrially in two steps from benzene:
First, benzene is nitrated using a mixture of concentrated mixture of nitric acid and sulfuric acid at 50 - 60 °C, which gives the electrophile NO2+ that attacks the benzene, displacing a proton H+ from that particular carbon atom. The resulting nitrobenzene is then treated with hydrogen gas, typically at 600 °C in presence of a nickel catalyst to give aniline, this conversion being called hydrogenation.
## Derivatives
Many derivatives of aniline can be prepared similarly. In commerce three brands of aniline are distinguished—aniline oil for blue, which is pure aniline; aniline oil for red, a mixture of equimolecular quantities of aniline and ortho- and para-toluidines; and aniline oil for safranine, which contains aniline and ortho-toluidine, and is obtained from the distillate (échappés) of the fuchsine fusion.
# Properties
## Oxidation
Aniline is colourless, it slowly oxidizes and resinifies in air, giving a red-brown tint to aged samples. The oxidation of aniline has been carefully investigated. In alkaline solution azobenzene results, while arsenic acid produces the violet-colouring matter violaniline. Chromic acid converts it into quinone, while chlorates, in the presence of certain metallic salts (especially of vanadium), give aniline black. Hydrochloric acid and potassium chlorate give chloranil. Potassium permanganate in neutral solution oxidizes it to nitrobenzene, in alkaline solution to azobenzene, ammonia and oxalic acid, in acid solution to aniline black. Hypochlorous acid gives 4-aminophenol and para-amino diphenylamine.
## Basicity
Aniline is a weak base. Aromatic amines such as aniline are generally much weaker bases than aliphatic amines. Aniline reacts with strong acids to form anilinium (or phenylammonium) ion (C6H5-NH3+). The sulfate forms beautiful white plates. Although aniline is weakly basic, it precipitates zinc, aluminium and ferric salts, and on warming expels ammonia from its salts.
## Acylation
Aniline reacts with carboxylic acids or more readily with acyl chlorides such as acetyl chloride to give amides. The amides formed from aniline are sometimes called "anilides", for example CH3-CO-NH-C6H5 is acetanilide. Antifebrin or acetanilide is obtained from acetic acid and aniline.
## N-alkyl derivatives
Aniline combines directly with alkyl iodides to form secondary and tertiary amines. Monomethyl and dimethyl aniline are colourless liquids prepared by heating aniline, aniline hydro-chloride and methyl alcohol in an autoclave at 220 °C. They are of great importance in the colour industry. Monomethyl aniline boils at 193-195 °C, dimethyl aniline at 192 °C.
## Sulfur derivatives
Boiled with carbon disulfide, it gives sulfocarbanilide (diphenyl thiourea), CS(NHC6H5)2, which may be decomposed into phenyl isothiocyanate, C6H5CNS, and triphenyl guanidine, C6H5N=C(NHC6H5)2.
Like phenols, aniline derivatives are highly susceptible to electrophilic substitution reactions. For example, sulfonation of aniline produces sulfanilic acid, which can be converted to sulfanilamide. Sulfanilamide is one of the sulfa drugs which were widely used as antibacterials in the early 20th century. Reaction with sulfuric acid at 180°C produces sulfanilic acid, NH2C6H4SO3H.
## Diazotization
Aniline and its ring-substituted derivatives react with nitrous acid to form diazonium salts. Through these, the -NH2 group of aniline can be conveniently converted to -OH, -CN, or a halide via Sandmeyer reactions.
## Other reactions
It reacts with nitrobenzene to produce phenazine in the Wohl-Aue reaction.
# Uses
Originally the great commercial value of aniline was due to the readiness with which it yields, directly or indirectly, dyestuffs. The discovery of mauve in 1856 by William Henry Perkin was the first of a series of dyestuffs which are now to be numbered by hundreds. Reference should be made to the articles dyeing, fuchsine, safranine, indulines, for more details on this subject. In addition to its use as a precursor to dyestuffs, it is a starting-product for the manufacture of many drugs such as paracetamol (acetaminophen, Tylenol).
It is used to stain neural RNA blue in the Nissl stain.
Currently the largest market for aniline is preparation of methylene diphenyl diisocyanate (MDI), some 85% of aniline serving this market. Other uses include rubber processing chemicals (9%), herbicides (2%), and dyes and pigments (2%).
# History
Aniline was first isolated from the destructive distillation of indigo in 1826 by Otto Unverdorben (Pogg. Ann., 1826, 8, p. 397), who named it crystalline. In 1834, Friedrich Runge (Pogg. Ann., 1834, 31, p. 65; 32, p. 331) isolated from coal tar a substance which produced a beautiful blue colour on treatment with chloride of lime; this he named kyanol or cyanol. In 1841, C. J. Fritzsche showed that by treating indigo with caustic potash it yielded an oil, which he named aniline, from the specific name of one of the indigo-yielding plants, Indigofera anil, anil being derived from the Sanskrit nīla, dark-blue, and nīlā, the indigo plant. About the same time N. N. Zinin found that on reducing nitrobenzene, a base was formed which he named benzidam. August Wilhelm von Hofmann investigated these variously prepared substances, and proved them to be identical (1855), and thenceforth they took their place as one body, under the name aniline or phenylamine.
Its first industrial-scale use was in the manufacture of mauveine, a purple dye discovered in 1856 by Hofmann's student William Henry Perkin. At the time of mauveine's discovery, aniline was an expensive laboratory compound, but it was soon prepared "by the ton" using a process previously discovered by Antoine Béchamp. The synthetic dye industry grew rapidly as new aniline-based dyes were discovered in the late 1850s and 1860s.
p-Toluidine, an aniline derivative, can be used in qualitative analysis to prepare carboxylic acid derivatives.
# Toxicology
Aniline is toxic by inhalation of the vapour, absorption through the skin or swallowing. It causes headache, drowsiness, cyanosis, mental confusion and in severe cases can cause convulsions. Prolonged exposure to the vapour or slight skin exposure over a period of time affects the nervous system and the blood, causing tiredness, loss of appetite, headache and dizziness.
Oil mixtures containing rapeseed oil denatured with aniline have been clearly linked by epidemiological and analytic chemical studies to the toxic oil syndrome that hit Spain in the spring and summer of 1981, in which 20,000 became acutely ill, 12,000 were hospitalized, and more than 350 died in the first year of the epidemic. The precise etiology though remains unknown.
Some authorities class aniline as a carcinogen, although the IARC lists it in Group 3 (not classifiable as to its carcinogenicity to humans) due to the limited and contradictory data available. | Aniline
Template:Chembox new
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Aniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. It is the simplest and one of the most imporant aromatic amines, being used as a precursor to more complex chemicals. Its main application is in the manufacture of polyurethane. Like most volatile amines, it possesses a somewhat unpleasant odour of rotten fish and also has a burning aromatic taste; it is a highly acrid poison. It ignites readily, burning with a smoky flame.
# Structure and synthesis
Consisting of a phenyl group attached to an amino group, aniline is produced industrially in two steps from benzene:
First, benzene is nitrated using a mixture of concentrated mixture of nitric acid and sulfuric acid at 50 - 60 °C, which gives the electrophile NO2+ that attacks the benzene, displacing a proton H+ from that particular carbon atom. The resulting nitrobenzene is then treated with hydrogen gas, typically at 600 °C in presence of a nickel catalyst to give aniline, this conversion being called hydrogenation.
## Derivatives
Many derivatives of aniline can be prepared similarly. In commerce three brands of aniline are distinguished—aniline oil for blue, which is pure aniline; aniline oil for red, a mixture of equimolecular quantities of aniline and ortho- and para-toluidines; and aniline oil for safranine, which contains aniline and ortho-toluidine, and is obtained from the distillate (échappés) of the fuchsine fusion.
# Properties
## Oxidation
Aniline is colourless, it slowly oxidizes and resinifies in air, giving a red-brown tint to aged samples. The oxidation of aniline has been carefully investigated. In alkaline solution azobenzene results, while arsenic acid produces the violet-colouring matter violaniline. Chromic acid converts it into quinone, while chlorates, in the presence of certain metallic salts (especially of vanadium), give aniline black. Hydrochloric acid and potassium chlorate give chloranil. Potassium permanganate in neutral solution oxidizes it to nitrobenzene, in alkaline solution to azobenzene, ammonia and oxalic acid, in acid solution to aniline black. Hypochlorous acid gives 4-aminophenol and para-amino diphenylamine.
## Basicity
Aniline is a weak base. Aromatic amines such as aniline are generally much weaker bases than aliphatic amines. Aniline reacts with strong acids to form anilinium (or phenylammonium) ion (C6H5-NH3+). The sulfate forms beautiful white plates. Although aniline is weakly basic, it precipitates zinc, aluminium and ferric salts, and on warming expels ammonia from its salts.
## Acylation
Aniline reacts with carboxylic acids[1] or more readily with acyl chlorides such as acetyl chloride to give amides. The amides formed from aniline are sometimes called "anilides", for example CH3-CO-NH-C6H5 is acetanilide. Antifebrin or acetanilide is obtained from acetic acid and aniline.
## N-alkyl derivatives
Aniline combines directly with alkyl iodides to form secondary and tertiary amines. Monomethyl and dimethyl aniline are colourless liquids prepared by heating aniline, aniline hydro-chloride and methyl alcohol in an autoclave at 220 °C. They are of great importance in the colour industry. Monomethyl aniline boils at 193-195 °C, dimethyl aniline at 192 °C.
## Sulfur derivatives
Boiled with carbon disulfide, it gives sulfocarbanilide (diphenyl thiourea), CS(NHC6H5)2, which may be decomposed into phenyl isothiocyanate, C6H5CNS, and triphenyl guanidine, C6H5N=C(NHC6H5)2.
Like phenols, aniline derivatives are highly susceptible to electrophilic substitution reactions. For example, sulfonation of aniline produces sulfanilic acid, which can be converted to sulfanilamide. Sulfanilamide is one of the sulfa drugs which were widely used as antibacterials in the early 20th century. Reaction with sulfuric acid at 180°C produces sulfanilic acid, NH2C6H4SO3H.
## Diazotization
Aniline and its ring-substituted derivatives react with nitrous acid to form diazonium salts. Through these, the -NH2 group of aniline can be conveniently converted to -OH, -CN, or a halide via Sandmeyer reactions.
## Other reactions
It reacts with nitrobenzene to produce phenazine in the Wohl-Aue reaction.
# Uses
Originally the great commercial value of aniline was due to the readiness with which it yields, directly or indirectly, dyestuffs. The discovery of mauve in 1856 by William Henry Perkin was the first of a series of dyestuffs which are now to be numbered by hundreds. Reference should be made to the articles dyeing, fuchsine, safranine, indulines, for more details on this subject. In addition to its use as a precursor to dyestuffs, it is a starting-product for the manufacture of many drugs such as paracetamol (acetaminophen, Tylenol).
It is used to stain neural RNA blue in the Nissl stain.
Currently the largest market for aniline is preparation of methylene diphenyl diisocyanate (MDI), some 85% of aniline serving this market. Other uses include rubber processing chemicals (9%), herbicides (2%), and dyes and pigments (2%).[2]
# History
Aniline was first isolated from the destructive distillation of indigo in 1826 by Otto Unverdorben (Pogg. Ann., 1826, 8, p. 397), who named it crystalline. In 1834, Friedrich Runge (Pogg. Ann., 1834, 31, p. 65; 32, p. 331) isolated from coal tar a substance which produced a beautiful blue colour on treatment with chloride of lime; this he named kyanol or cyanol. In 1841, C. J. Fritzsche showed that by treating indigo with caustic potash it yielded an oil, which he named aniline, from the specific name of one of the indigo-yielding plants, Indigofera anil, anil being derived from the Sanskrit nīla, dark-blue, and nīlā, the indigo plant. About the same time N. N. Zinin found that on reducing nitrobenzene, a base was formed which he named benzidam. August Wilhelm von Hofmann investigated these variously prepared substances, and proved them to be identical (1855), and thenceforth they took their place as one body, under the name aniline or phenylamine.
Its first industrial-scale use was in the manufacture of mauveine, a purple dye discovered in 1856 by Hofmann's student William Henry Perkin. At the time of mauveine's discovery, aniline was an expensive laboratory compound, but it was soon prepared "by the ton" using a process previously discovered by Antoine Béchamp.[3] The synthetic dye industry grew rapidly as new aniline-based dyes were discovered in the late 1850s and 1860s.
p-Toluidine, an aniline derivative, can be used in qualitative analysis to prepare carboxylic acid derivatives.
# Toxicology
Aniline is toxic by inhalation of the vapour, absorption through the skin or swallowing. It causes headache, drowsiness, cyanosis, mental confusion and in severe cases can cause convulsions. Prolonged exposure to the vapour or slight skin exposure over a period of time affects the nervous system and the blood, causing tiredness, loss of appetite, headache and dizziness.[4]
Oil mixtures containing rapeseed oil denatured with aniline have been clearly linked by epidemiological and analytic chemical studies to the toxic oil syndrome that hit Spain in the spring and summer of 1981, in which 20,000 became acutely ill, 12,000 were hospitalized, and more than 350 died in the first year of the epidemic. The precise etiology though remains unknown.
Some authorities class aniline as a carcinogen, although the IARC lists it in Group 3 (not classifiable as to its carcinogenicity to humans) due to the limited and contradictory data available. | https://www.wikidoc.org/index.php/Anilide | |
4b0a3fd2e9497631076f359150c464096835d81d | wikidoc | Anismus | Anismus
# Overview
Anismus (or dyssynergic defecation) refers to the failure of the normal relaxation of pelvic floor muscles during attempted defecation.
Anismus can occur in both children and adults, and in both men and women (although it is more common in women). It can be caused by physical defects or it can occur for other reasons or unknown reasons. Anismus that has a behavioral cause could be viewed as having similarities with parcopresis, or psychogenic fecal retention.
Symptoms include tenesmus (a sensation where a mass is felt to remain in rectum after defecation) and constipation. Retention of stool may result in fecal loading (retention of a mass of stool of any consistency) or fecal impaction (retention of a mass of hard stool). This mass may stretch the walls of the rectum and colon, causing megarectum and/or megacolon respectively. Liquid stool may leak around a fecal impaction, possibly causing degrees of liquid fecal incontinence. This is usually termed encopresis or soiling in children, and fecal leakage, soiling or liquid fecal incontinence in adults.
Anismus is usually treated with adjustments to the diet, such as dietary fiber supplementation. It can also be treated with a type of biofeedback therapy, where a sensor probe is inserted in the patient's anal canal and records the pressures exerted by the pelvic floor muscles. These pressures are visually fed back to the patient via a monitor who is able to regain the normal coordinated movement of the muscles after a few sessions.
Some researchers have suggested that anismus is an over-diagnosed condition, since the standard investigations or digital rectal examination and anorectal manometry were shown to cause paradoxical sphincter contraction in healthy controls, who did not have constipation or incontinence. Due to the invasive and perhaps uncomfortable nature of these investigations, the pelvic floor musculature is thought to behave differently than under normal circumstances. These researchers went on to conclude that paradoxical pelvic floor contraction common finding in healthy controls as well as in patients with chronic constipation and stool incontinence, and it represents a non-specific finding or laboratory artifact related to untoward conditions during examination, and that true anismus is actually rare.
# Historical Perspective
Paradoxical anal contraction during attempted defecation in constipated patients was first described in a paper in 1985, when the term anismus was first used. The researchers drew analogies to a condition called vaginismus, which involves paroxysmal contraction of pubococcygeus (another muscle of the pelvic floor). These researchers felt that this condition was a spastic dysfunction of the anus, analogous to ‘vaginismus’. However, the term anismus implies a psychogenic etiology, which is not true although psychological dysfunction has been described in these patients. Hence:
Latin ani - "of the anus"
Latin spasmus - "spasm"
(Derived by extrapolation with the term vaginismus, which in turn is from the Latin vagina - "sheath" + spasmus - "spasm")
Many terms have been used synonymously to refer to this condition, some inappropriately. The term "anismus" has been criticised as it implies a psychogenic cause. As stated in the Rome II criteria, the term "dyssynergic defecation" is preferred to "pelvic floor dyssynergia" because many patients with dyssynergic defecation do not report sexual or urinary symptoms, meaning that only the defecation mechanism is affected.
Other synonyms include:
- Dyskinetic puborectalis
- Puborectalis syndrome
- Paradoxical puborectalis
- Nonrelaxing puborectalis
- Paradoxal puborectal contraction
- Spastic pelvic floor syndrome,
- Anal sphincter dyssynergia
- Paradoxical pelvic floor contraction
# Classification
Anismus is classified as a functional defecation disorder. It is also a type of rectal outlet obstruction (a functional outlet obstruction). Where anismus causes constipation, it is an example of functional constipation. Some authors describe an "obstructed defecation syndrome", of which anismus is a cause.
The Rome classification subdivides functional defecation disorders into 3 types, however the symptoms the patient experiences are identical.
- Type I: paradoxical paradoxical contraction of the pelvic floor muscles during attempted defecation
- Type II: inadequate propulsive forces during attempted defecation (inadequate defecatory propulsion)
- Type III: impaired relaxation with adequate propulsion
It can be seen from the above classification that many of the terms that have been used interchangeably with anismus are inappropriately specific and neglect the concept of impaired propulsion. Similarly, some of the definitions that have been offered are also too restrictive.
# Causes
To understand the etiology of anismus, an understanding of normal colorectal anatomy and physiology, including the normal defecation mechanism, is helpful. The relevant anatomy includes: the rectum, the anal canal and the muscles of the pelvic floor, especially puborectalis and the external anal sphincter.
The rectum is a section of bowel situated just above the anal canal and distal to the sigmoid colon. It is believed to act as a reservoir to store stool until it fills past a certain volume, at which time the defecation reflexes are stimulated. In healthy individuals, defecation can be temporarily delayed until it is socially acceptable to defecate. In continent individuals, the rectum is able to expand to a degree to accommodate this function.
The anal canal is the short straight section of bowel between the rectum and the anus. It can be defined functionally as the distance between the anorectal ring and the end of the internal anal sphincter. The internal anal sphincter forms the walls of the anal canal. The internal anal sphincter is not under voluntary control, and in normal persons it is contracted at all times except when there is a need to defecate. This means that the internal anal sphincter contributes more to the resting tone of the anal canal than the external anal sphincter. The internal sphincter is responsible for creating a watertight seal, and therefore provides continence of liquid stool elements.
Puborectalis is one of the muscles of the pelvic floor. It is skeletal muscle, meaning it is under voluntary control. The puborectalis originates on the posterior aspect of the pubic bone, and runs backwards, looping around the bowel.
The point at which the rectum joins the anal canal is known as the anorectal ring, which is at the level that the puborectalis muscle loops around the bowel from in front. This arrangement means that when puborectalis is contracted, it pulls the junction of the rectum and the anal canal forwards, creating an angle in the bowel called the anorectal angle. This angle prevents the movement of stool stored in the rectum moving into the anal canal. It is thought to be responsible for gross continence of solid stool. Some believe the anorectal angle is one of the most important contributors to continence.
Conversely, relaxation of the puborectalis reduces the pull on the junction of the rectum and the anal canal,
causing the anorectal angle to straighten out. A squatting posture is also known to straighten the anorectal angle, meaning that less effort is required to defecate when in this position.
Distension of the rectum normally causes the internal anal sphincter to relax (Rectoanal inhibitory response, RAIR) and the external anal sphincter initially to contract (rectoanal excitatory reflex, RAER). The relaxation of the internal anal sphincter is an involuntary response. The external anal sphincter, by contrast, is made up of skeletal (or striated muscle) and is therefore under voluntary control. It is able to contract vigorously for a short time. Contraction of the external sphincter can defer defecation for a time by pushing stool from the anal canal back into the rectum.
Once the voluntary signal to defecate is sent back from the brain, the abdominal muscles contract (straining) causing the intra-abdominal pressure to increase. the pelvic floor is lowered causing the ano rectal angle to straighten out from ~90o to <15o and the external anal sphincter relaxes. The rectum now contracts and shortens in peristaltic waves, thus forcing fecal material out of the rectum, through the anal canal and out of the anus. The internal and external anal sphincters along with the puborectalis muscle allow the feces to be passed by pulling the anus up over the exiting feces in shortening and contracting actions.
In patients with anismus, the puborectalis and the external anal sphincter muscles fail to relax, with resultant failure of the anorectal angle to straighten out and facilitate evacuation of feces from the rectum. These muscles may even contract when they should relax (paradoxical contraction), and this not only fails to straighten out the anorectal angle, but causes it to become more acute and offer greater obstruction to evacuation.
As these muscles are under voluntary control, the failure of muscular relaxation or paradoxical contraction that is characteristic of anismus can be thought of as either maladaptive behavior or a loss of voluntary control of these muscles. Others claim that puborectalis can become hypertrophied (enlarged) or fibrosis (replacement of muscle tissue with a more fibrous tissue), which reduces voluntary control over the muscle.
Anismus could be thought of as the patient "forgetting" how to push correctly, i.e. straining against a contracted pelvic floor, instead of increasing abdominal cavity pressures and lowering pelvic cavity pressures. It may be that this scenario develops as a result of stress. For example, one study reported that animus was strongly associated with sexual abuse in women. One paper stated that events such as pregnancy, childbirth, gynaecological descent or neurogenic disturbances of the brain-bowel axis could lead to a "functional obstructed defecation syndrome" (including anismus). Anismus may develop in persons with extrapyramidal motor disturbance due to Parkinson's disease. This represents a type of focal dystonia. Anismus may also occur with anorectal malformation, rectocele, rectal prolapse and rectal ulcer.
In many cases however, the underlying pathophysiology in patients presenting with obstructed defecation cannot be determined.
Some authors have commented that the "puborectalis paradox" and "spastic pelvic floor" concepts have no objective data to support their validity. They state that "new evidence showing that defecation is an integrated process of colonic and rectal emptying suggests that anismus may be much more complex than a simple disorder of the pelvic floor muscles."
# Natural History, Complications and Porgnosis
Persistent failure to fully evacuate stool may lead to retention of a mass of stool in the rectum (fecal loading), which can become hardened, forming a fecal impaction or even fecoliths.
Liquid stool elements may leak around the retained fecal mass, which may lead to paradoxical diarrhoea and/or fecal leakage (usually known as encopresis in children and fecal leakage in adults).
When anismus occurs in the context of intractable encopresis (as it often does), resolution of anismus may be insufficient to resolve encopresis. For this reason, and because biofeedback training is invasive, expensive, and labor intensive, biofeedback training is not recommended for treatment of encopresis with anismus.
The walls of the rectum may become stretched, known as megarectum.
# Diagnosis
## Definition
Several definitions have been offered:
- "Absence of normal relaxation of pelvic floor muscles during defecation, resulting in rectal outlet obstruction".
- "Malfunction (a focal dystonia) of the external anal sphincter and puborectalis muscle during defecation".
- " failure of muscle to relax, resulting in maintenance of the anorectal angle and the difficulty with initiating and completing bowel movements".
- " failure of relaxation (or paradoxic contraction) of the puborectalis muscle sling during defaecation, attempted defaecation or straining."
## History and Symptoms
Symptoms include:
- Straining to pass fecal material
- Tenesmus (a feeling of incomplete evacuation)
- Feeling of anorectal obstruction/blockage
- Digital maneuvers needed to aid defecation
- Difficulty initiating and completing bowel movements
# Diagnosis
The Rome classification diagnostic criteria for functional defecation disorders is as follows:
- Patient must satisfy diagnostic criteria for functional constipation
- During repeated attempts to defecate must have at least 2 of the following:
- Evidence of impaired evacuation, based on balloon expulsion test or imaging
- Inappropriate contraction of the pelvic floor muscles (ie, anal sphincter or puborectalis) or less than 20% relaxation of basal resting sphincter pressure by manometry, imaging, or electromyography
- Inadequate propulsive forces assessed by manometry or imaging
The diagnostic criteria for dyssynergic defecation is given as "inappropriate contraction of the pelvic floor
-r less than 20% relaxation of basal resting sphincter pressure with adequate propulsive forces during attempted defecation."
The diagnostic criteria for inadequate defecatory Propulsion is given as "inadequate propulsive forces with or without inappropriate contraction or less than 20% relaxation of the anal sphincter during attempted defecation."
The Rome criteria recommend that anorectal testing is not usually indicated in patients with symptoms of until patients have failed conservative
treatment (e.g., increased dietary fiber and liquids; elimination
-f medications with constipating side effects
whenever possible).
Various investigations have been recommended in the diagnosis of anisumus.
## Digital rectal examination
Physical examination can rule out anismus (by identifying another cause) but is not sufficient to diagnose anismus.
## Anorectal manometry
## Evacuation proctography
defecating proctogram), and MRI defecography
## Balloon expulsion test
## Rectal cooling test
The rectal cooling test is suggested to differentiate between rectal inertia and impaired relaxation/paradoxical contraction
Other techniques include manometry, balloon expulsion test, evacuation proctography (see defecating proctogram), and MRI defecography. Diagnostic criteria are: fulfillment of criteria for functional constipation, manometric and/or EMG and/or radiological evidence (2 out of 3), evidence of adequate expulsion force, and evidence of incomplete evacuation. Recent dynamic imaging studies have shown that in persons diagnosed with anismus the anorectal angle during attempted defecation is abnormal, and this is due to abnormal (paradoxical) movement of the puborectalis muscle.
# Treatment
Initial steps to alleviate anismus include dietary adjustments and simple adjustments when attempting to defecate. Supplementation with a bulking agent such as psyllium 3500 mg per day will make stool more bulky, which decreases the effort required to evacuate. Similarly, exercise and adequate hydration may help to optimise stool form. The anorectal angle has been shown to flatten out when in a squatting position, and is thus recommended for patients with functional outlet obstruction like anismus. If the patient is unable to assume a squatting postures due to mobility issues, a low stool can be used to raise the feet when sitting, which effectively achieves a similar position.
Treatments for anismus include biofeedback retraining, botox injections, and surgical resection. Anismus sometimes occurs together with other conditions that limit (see contraindication) the choice of treatments. Thus, thorough evaluation is recommended prior to treatment.
Biofeedback training for treatment of anismus is highly effective and considered the gold standard therapy by many.
Others however, reported that biofeedback had a limited therapeutic effect.
Injections of botulin toxin type-A into the puborectalis muscle are very effective in the short term, and somewhat effective in the long term. Injections may be helpful when used together with biofeedback training.
Historically, the standard treatment was surgical resection of the puborectalis muscle, which sometimes resulted in fecal incontinence. Recently, partial resection (partial division) has been reported to be effective in some cases.
# Related Chapters
- Defecation postures
- Dystonia
- Parcopresis | Anismus
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kalsang Dolma, M.B.B.S.[2]
# Overview
Anismus (or dyssynergic defecation) refers to the failure of the normal relaxation of pelvic floor muscles during attempted defecation.
Anismus can occur in both children and adults, and in both men and women (although it is more common in women). It can be caused by physical defects or it can occur for other reasons or unknown reasons. Anismus that has a behavioral cause could be viewed as having similarities with parcopresis, or psychogenic fecal retention.
Symptoms include tenesmus (a sensation where a mass is felt to remain in rectum after defecation) and constipation. Retention of stool may result in fecal loading (retention of a mass of stool of any consistency) or fecal impaction (retention of a mass of hard stool). This mass may stretch the walls of the rectum and colon, causing megarectum and/or megacolon respectively. Liquid stool may leak around a fecal impaction, possibly causing degrees of liquid fecal incontinence. This is usually termed encopresis or soiling in children, and fecal leakage, soiling or liquid fecal incontinence in adults.
Anismus is usually treated with adjustments to the diet, such as dietary fiber supplementation. It can also be treated with a type of biofeedback therapy, where a sensor probe is inserted in the patient's anal canal and records the pressures exerted by the pelvic floor muscles. These pressures are visually fed back to the patient via a monitor who is able to regain the normal coordinated movement of the muscles after a few sessions.
Some researchers have suggested that anismus is an over-diagnosed condition, since the standard investigations or digital rectal examination and anorectal manometry were shown to cause paradoxical sphincter contraction in healthy controls, who did not have constipation or incontinence.[1] Due to the invasive and perhaps uncomfortable nature of these investigations, the pelvic floor musculature is thought to behave differently than under normal circumstances. These researchers went on to conclude that paradoxical pelvic floor contraction common finding in healthy controls as well as in patients with chronic constipation and stool incontinence, and it represents a non-specific finding or laboratory artifact related to untoward conditions during examination, and that true anismus is actually rare.
# Historical Perspective
Paradoxical anal contraction during attempted defecation in constipated patients was first described in a paper in 1985, when the term anismus was first used.[2] The researchers drew analogies to a condition called vaginismus, which involves paroxysmal contraction of pubococcygeus (another muscle of the pelvic floor). These researchers felt that this condition was a spastic dysfunction of the anus, analogous to ‘vaginismus’. However, the term anismus implies a psychogenic etiology, which is not true although psychological dysfunction has been described in these patients. Hence:
Latin ani - "of the anus"
Latin spasmus - "spasm"
(Derived by extrapolation with the term vaginismus, which in turn is from the Latin vagina - "sheath" + spasmus - "spasm")
Many terms have been used synonymously to refer to this condition, some inappropriately. The term "anismus" has been criticised as it implies a psychogenic cause.[3] As stated in the Rome II criteria, the term "dyssynergic defecation" is preferred to "pelvic floor dyssynergia" because many patients with dyssynergic defecation do not report sexual or urinary symptoms,[4] meaning that only the defecation mechanism is affected.
Other synonyms include:
- Dyskinetic puborectalis [5]
- Puborectalis syndrome [6]
- Paradoxical puborectalis [5]
- Nonrelaxing puborectalis [5]
- Paradoxal puborectal contraction [7]
- Spastic pelvic floor syndrome,[8]
- Anal sphincter dyssynergia [9]
- Paradoxical pelvic floor contraction [5]
# Classification
Anismus is classified as a functional defecation disorder. It is also a type of rectal outlet obstruction (a functional outlet obstruction). Where anismus causes constipation, it is an example of functional constipation. Some authors describe an "obstructed defecation syndrome", of which anismus is a cause.[10]
The Rome classification subdivides functional defecation disorders into 3 types,[4] however the symptoms the patient experiences are identical.[11]
- Type I: paradoxical paradoxical contraction of the pelvic floor muscles during attempted defecation
- Type II: inadequate propulsive forces during attempted defecation (inadequate defecatory propulsion)
- Type III: impaired relaxation with adequate propulsion
It can be seen from the above classification that many of the terms that have been used interchangeably with anismus are inappropriately specific and neglect the concept of impaired propulsion. Similarly, some of the definitions that have been offered are also too restrictive.
# Causes
To understand the etiology of anismus, an understanding of normal colorectal anatomy and physiology, including the normal defecation mechanism, is helpful. The relevant anatomy includes: the rectum, the anal canal and the muscles of the pelvic floor, especially puborectalis and the external anal sphincter.
The rectum is a section of bowel situated just above the anal canal and distal to the sigmoid colon. It is believed to act as a reservoir to store stool until it fills past a certain volume, at which time the defecation reflexes are stimulated.[12] In healthy individuals, defecation can be temporarily delayed until it is socially acceptable to defecate. In continent individuals, the rectum is able to expand to a degree to accommodate this function.
The anal canal is the short straight section of bowel between the rectum and the anus. It can be defined functionally as the distance between the anorectal ring and the end of the internal anal sphincter. The internal anal sphincter forms the walls of the anal canal. The internal anal sphincter is not under voluntary control, and in normal persons it is contracted at all times except when there is a need to defecate. This means that the internal anal sphincter contributes more to the resting tone of the anal canal than the external anal sphincter. The internal sphincter is responsible for creating a watertight seal, and therefore provides continence of liquid stool elements.
Puborectalis is one of the muscles of the pelvic floor. It is skeletal muscle, meaning it is under voluntary control. The puborectalis originates on the posterior aspect of the pubic bone, and runs backwards, looping around the bowel.
The point at which the rectum joins the anal canal is known as the anorectal ring, which is at the level that the puborectalis muscle loops around the bowel from in front. This arrangement means that when puborectalis is contracted, it pulls the junction of the rectum and the anal canal forwards, creating an angle in the bowel called the anorectal angle. This angle prevents the movement of stool stored in the rectum moving into the anal canal. It is thought to be responsible for gross continence of solid stool. Some believe the anorectal angle is one of the most important contributors to continence.[13]
Conversely, relaxation of the puborectalis reduces the pull on the junction of the rectum and the anal canal,
causing the anorectal angle to straighten out. A squatting posture is also known to straighten the anorectal angle, meaning that less effort is required to defecate when in this position.[14]
Distension of the rectum normally causes the internal anal sphincter to relax (Rectoanal inhibitory response, RAIR) and the external anal sphincter initially to contract (rectoanal excitatory reflex, RAER). The relaxation of the internal anal sphincter is an involuntary response. The external anal sphincter, by contrast, is made up of skeletal (or striated muscle) and is therefore under voluntary control. It is able to contract vigorously for a short time. Contraction of the external sphincter can defer defecation for a time by pushing stool from the anal canal back into the rectum.
Once the voluntary signal to defecate is sent back from the brain, the abdominal muscles contract (straining) causing the intra-abdominal pressure to increase. the pelvic floor is lowered causing the ano rectal angle to straighten out from ~90o to <15o and the external anal sphincter relaxes. The rectum now contracts and shortens in peristaltic waves, thus forcing fecal material out of the rectum, through the anal canal and out of the anus. The internal and external anal sphincters along with the puborectalis muscle allow the feces to be passed by pulling the anus up over the exiting feces in shortening and contracting actions.
In patients with anismus, the puborectalis and the external anal sphincter muscles fail to relax, with resultant failure of the anorectal angle to straighten out and facilitate evacuation of feces from the rectum. These muscles may even contract when they should relax (paradoxical contraction), and this not only fails to straighten out the anorectal angle, but causes it to become more acute and offer greater obstruction to evacuation.
As these muscles are under voluntary control, the failure of muscular relaxation or paradoxical contraction that is characteristic of anismus can be thought of as either maladaptive behavior or a loss of voluntary control of these muscles. Others claim that puborectalis can become hypertrophied (enlarged) or fibrosis (replacement of muscle tissue with a more fibrous tissue), which reduces voluntary control over the muscle.
Anismus could be thought of as the patient "forgetting" how to push correctly, i.e. straining against a contracted pelvic floor, instead of increasing abdominal cavity pressures and lowering pelvic cavity pressures. It may be that this scenario develops as a result of stress. For example, one study reported that animus was strongly associated with sexual abuse in women.[15] One paper stated that events such as pregnancy, childbirth, gynaecological descent or neurogenic disturbances of the brain-bowel axis could lead to a "functional obstructed defecation syndrome" (including anismus).[7] Anismus may develop in persons with extrapyramidal motor disturbance due to Parkinson's disease.[16] This represents a type of focal dystonia.[17] Anismus may also occur with anorectal malformation, rectocele,[18] rectal prolapse[19] and rectal ulcer.[19]
In many cases however, the underlying pathophysiology in patients presenting with obstructed defecation cannot be determined.[20]
Some authors have commented that the "puborectalis paradox" and "spastic pelvic floor" concepts have no objective data to support their validity. They state that "new evidence showing that defecation is an integrated process of colonic and rectal emptying suggests that anismus may be much more complex than a simple disorder of the pelvic floor muscles." [20]
# Natural History, Complications and Porgnosis
Persistent failure to fully evacuate stool may lead to retention of a mass of stool in the rectum (fecal loading), which can become hardened, forming a fecal impaction or even fecoliths.
Liquid stool elements may leak around the retained fecal mass, which may lead to paradoxical diarrhoea and/or fecal leakage (usually known as encopresis in children and fecal leakage in adults).[21][22][23][24]
When anismus occurs in the context of intractable encopresis (as it often does), resolution of anismus may be insufficient to resolve encopresis.[25] For this reason, and because biofeedback training is invasive, expensive, and labor intensive, biofeedback training is not recommended for treatment of encopresis with anismus.
The walls of the rectum may become stretched, known as megarectum.[26]
# Diagnosis
## Definition
Several definitions have been offered:
- "Absence of normal relaxation of pelvic floor muscles during defecation, resulting in rectal outlet obstruction".[5]
- "Malfunction (a focal dystonia) of the external anal sphincter and puborectalis muscle during defecation".
- "[...] failure of [the external anal sphincter and puborectalis] muscle[s] to relax, resulting in maintenance of the anorectal angle and the difficulty with initiating and completing bowel movements".[6]
- "[...] failure of relaxation (or paradoxic contraction) of the puborectalis muscle sling during defaecation, attempted defaecation or straining."[10]
## History and Symptoms
Symptoms include:
- Straining to pass fecal material [27]
- Tenesmus (a feeling of incomplete evacuation) [27]
- Feeling of anorectal obstruction/blockage [27]
- Digital maneuvers needed to aid defecation [27]
- Difficulty initiating and completing bowel movements[6]
# Diagnosis
The Rome classification diagnostic criteria for functional defecation disorders is as follows:[4]
- Patient must satisfy diagnostic criteria for functional constipation
- During repeated attempts to defecate must have at least 2 of the following:
- Evidence of impaired evacuation, based on balloon expulsion test or imaging
- Inappropriate contraction of the pelvic floor muscles (ie, anal sphincter or puborectalis) or less than 20% relaxation of basal resting sphincter pressure by manometry, imaging, or electromyography
- Inadequate propulsive forces assessed by manometry or imaging
The diagnostic criteria for dyssynergic defecation is given as "inappropriate contraction of the pelvic floor
or less than 20% relaxation of basal resting sphincter pressure with adequate propulsive forces during attempted defecation." [4]
The diagnostic criteria for inadequate defecatory Propulsion is given as "inadequate propulsive forces with or without inappropriate contraction or less than 20% relaxation of the anal sphincter during attempted defecation." [4]
The Rome criteria recommend that anorectal testing is not usually indicated in patients with symptoms of until patients have failed conservative
treatment (e.g., increased dietary fiber and liquids; elimination
of medications with constipating side effects
whenever possible).
Various investigations have been recommended in the diagnosis of anisumus.
## Digital rectal examination
Physical examination can rule out anismus (by identifying another cause) but is not sufficient to diagnose anismus.
## Anorectal manometry
## Evacuation proctography
defecating proctogram), and MRI defecography
## Balloon expulsion test
## Rectal cooling test
The rectal cooling test is suggested to differentiate between rectal inertia and impaired relaxation/paradoxical contraction [28]
Other techniques include manometry, balloon expulsion test, evacuation proctography (see defecating proctogram), and MRI defecography.[29] Diagnostic criteria are: fulfillment of criteria for functional constipation, manometric and/or EMG and/or radiological evidence (2 out of 3), evidence of adequate expulsion force, and evidence of incomplete evacuation.[29] Recent dynamic imaging studies have shown that in persons diagnosed with anismus the anorectal angle during attempted defecation is abnormal, and this is due to abnormal (paradoxical) movement of the puborectalis muscle.[30][31][32]
# Treatment
Initial steps to alleviate anismus include dietary adjustments and simple adjustments when attempting to defecate. Supplementation with a bulking agent such as psyllium 3500 mg per day will make stool more bulky, which decreases the effort required to evacuate.[5] Similarly, exercise and adequate hydration may help to optimise stool form. The anorectal angle has been shown to flatten out when in a squatting position, and is thus recommended for patients with functional outlet obstruction like anismus.[13] If the patient is unable to assume a squatting postures due to mobility issues, a low stool can be used to raise the feet when sitting, which effectively achieves a similar position.
Treatments for anismus include biofeedback retraining, botox injections, and surgical resection. Anismus sometimes occurs together with other conditions that limit (see contraindication) the choice of treatments. Thus, thorough evaluation is recommended prior to treatment.[33]
Biofeedback training for treatment of anismus is highly effective and considered the gold standard therapy by many.[25][34][35]
Others however, reported that biofeedback had a limited therapeutic effect.[36]
Injections of botulin toxin type-A into the puborectalis muscle are very effective in the short term, and somewhat effective in the long term.[37] Injections may be helpful when used together with biofeedback training.[38][39]
Historically, the standard treatment was surgical resection of the puborectalis muscle, which sometimes resulted in fecal incontinence. Recently, partial resection (partial division) has been reported to be effective in some cases.[36][40]
# Related Chapters
- Defecation postures
- Dystonia
- Parcopresis | https://www.wikidoc.org/index.php/Anismus | |
3aec572ec517ae2af55c246b8358eb31107fd957 | wikidoc | Ankyrin | Ankyrin
Ankyrins are a family of proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane cytoskeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral membrane proteins. This linkage is required to maintain the integrity of the plasma membranes and to anchor specific ion channels, ion exchangers and ion transporters in the plasma membrane. The name is derived from the Greek word for "fused".
# Structure
Ankyrins contain four functional domains: an N-terminal domain that contains 24 tandem ankyrin repeats, a central domain that binds to spectrin, a death domain that binds to proteins involved in apoptosis, and a C-terminal regulatory domain that is highly variable between different ankyrin proteins.
# Membrane protein recognition
The 24 tandem ankyrin repeats are responsible for the recognition of a wide range of membrane proteins. These 24 repeats contain 3 structurally distinct binding sites ranging from repeat 1-14. These binding sites are quasi-independent of each other and can be used in combination. The interactions the sites use to bind to membrane proteins are non-specific and consist of: hydrogen bonding, hydrophobic interactions and electrostatic interactions. These non-specific interactions give ankyrin the property to recognise a large range of proteins as the sequence doesn't have to be conserved, just the properties of the amino acids. The quasi-independence means that if a binding site is not used, it won't have a large effect on the overall binding. These two properties in combination give rise to large repertoire of proteins ankyrin can recognise.
# Subtypes
Ankyrins are encoded by three genes (ANK1, ANK2 and ANK3) in mammals. Each gene in turn produces multiple proteins through alternative splicing.
## ANK1
The ANK1 gene encodes the AnkyrinR proteins. AnkyrinR was first characterized in human erythrocytes, where this ankyrin was referred to as erythrocyte ankyrin or band2.1. AnkyrinR enables erythrocytes to resist shear forces experienced in the circulation. Individuals with reduced or defective ankyrinR have a form of hemolytic anemia termed hereditary spherocytosis. In erythrocytes, AnkyrinR links the membrane skeleton to the Cl−/HCO3− anion exchanger.
Ankyrin 1 links membrane receptor CD44 to the inositol triphosphate receptor and the cytoskeleton.
It has been suggested that Ankyrin 1 interacts with KAHRP (shown via selective pull-downs, SPR and ELISA).
## ANK2
Subsequently, ankyrinB proteins (products of the ANK2 gene) were identified in brain and muscle. AnkyrinB and AnkyrinG proteins are required for the polarized distribution of many membrane proteins including the Na+/K+ ATPase, the voltage gated Na+ channel and the Na+/Ca2+ exchanger.
## ANK3
AnkyrinG proteins (products of the ANK3 gene) were identified in epithelial cells and neurons. A large-scale genetic analysis conducted in 2008 shows the possibility that ANK3 is involved in bipolar disorder. | Ankyrin
Ankyrins are a family of proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane cytoskeleton.[2] Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral membrane proteins. This linkage is required to maintain the integrity of the plasma membranes and to anchor specific ion channels, ion exchangers and ion transporters in the plasma membrane. The name is derived from the Greek word for "fused".
# Structure
Ankyrins contain four functional domains: an N-terminal domain that contains 24 tandem ankyrin repeats, a central domain that binds to spectrin, a death domain that binds to proteins involved in apoptosis, and a C-terminal regulatory domain that is highly variable between different ankyrin proteins.[2]
# Membrane protein recognition
The 24 tandem ankyrin repeats are responsible for the recognition of a wide range of membrane proteins. These 24 repeats contain 3 structurally distinct binding sites ranging from repeat 1-14. These binding sites are quasi-independent of each other and can be used in combination. The interactions the sites use to bind to membrane proteins are non-specific and consist of: hydrogen bonding, hydrophobic interactions and electrostatic interactions. These non-specific interactions give ankyrin the property to recognise a large range of proteins as the sequence doesn't have to be conserved, just the properties of the amino acids. The quasi-independence means that if a binding site is not used, it won't have a large effect on the overall binding. These two properties in combination give rise to large repertoire of proteins ankyrin can recognise.
# Subtypes
Ankyrins are encoded by three genes (ANK1, ANK2 and ANK3) in mammals. Each gene in turn produces multiple proteins through alternative splicing.
## ANK1
The ANK1 gene encodes the AnkyrinR proteins. AnkyrinR was first characterized in human erythrocytes, where this ankyrin was referred to as erythrocyte ankyrin or band2.1.[3] AnkyrinR enables erythrocytes to resist shear forces experienced in the circulation. Individuals with reduced or defective ankyrinR have a form of hemolytic anemia termed hereditary spherocytosis.[4] In erythrocytes, AnkyrinR links the membrane skeleton to the Cl−/HCO3− anion exchanger.[5]
Ankyrin 1 links membrane receptor CD44 to the inositol triphosphate receptor and the cytoskeleton.[6]
It has been suggested that Ankyrin 1 interacts with KAHRP (shown via selective pull-downs, SPR and ELISA).[7]
## ANK2
Subsequently, ankyrinB proteins (products of the ANK2 gene[8]) were identified in brain and muscle. AnkyrinB and AnkyrinG proteins are required for the polarized distribution of many membrane proteins including the Na+/K+ ATPase, the voltage gated Na+ channel and the Na+/Ca2+ exchanger.
## ANK3
AnkyrinG proteins (products of the ANK3 gene[9]) were identified in epithelial cells and neurons. A large-scale genetic analysis conducted in 2008 shows the possibility that ANK3 is involved in bipolar disorder.[10][11] | https://www.wikidoc.org/index.php/Ankyrin | |
aeb0223458fded220fdf44c8d0d491452fe4220b | wikidoc | Anna O. | Anna O.
Anna O. was the pseudonym of a patient of Josef Breuer, who published her case study in his book Studies on Hysteria, written in collaboration with Sigmund Freud.
Anna O was, in fact, Bertha Pappenheim (1859-1936), an Austrian-Jewish feminist and the founder of the Jüdischer Frauenbund, treated by Breuer for severe cough, paralysis of the extremities on the right side of her body, and disturbances of vision, hearing, and speech, as well as hallucination and loss of consciousness. She was diagnosed with hysteria. Freud implies that her illness was a result of the grief felt over her father's real and physical illness that later led to his death.
Her treatment is regarded as marking the beginning of psychoanalysis. Breuer observed that whilst she experienced 'absences' (a change of personality accompanied by confusion), she would mutter words or phrases to herself. In inducing her to a state of hypnosis, Breuer found that these words were "profoundly melancholy phantasies...sometimes characterized by poetic beauty". Free Association came into being after Anna/Bertha decided (with Breuer's input) to end her hypnosis sessions and merely talk to Breuer, saying anything that came into her mind. She called this method of communication "chimney sweeping", and this served as the beginning of free association.
Anna's/Bertha's case also shed light for the first time on the phenomenon called transference, where the patient's feelings toward a significant figure in his/her life are redirected onto the therapist. By transference, Anna imagined to be pregnant with the doctor's baby. She experienced nausea and all the pregnancy symptoms. After this incident, Breuer stopped treating her.
Historical records since showed that when Breuer stopped treating Anna O. she was not becoming better but progressively worse. In fact she was ultimately institutionalised: "Breuer told Freud that she was deranged; he hoped she would die to end her suffering".
She later recovered over time and led a productive life: the West German government issued a postage stamp in honour of her contributions to the field of social work.
According to current research, "examination of the neurological details suggests that Anna suffered from complex partial seizures exacerbated by drug dependence." In other words, her illness was not, as Freud suggested, psychological, but neurological. Many believe that Freud misdiagnosed her, and she in fact suffered from temporal lobe epilepsy, and many of her symptoms, including imagined smells, are common symptoms of types of epilepsy.
Pappenheim under her real name translated the diary of her ancestor Gluckel of Hameln. | Anna O.
Anna O. was the pseudonym of a patient of Josef Breuer, who published her case study in his book Studies on Hysteria, written in collaboration with Sigmund Freud.
Anna O was, in fact, Bertha Pappenheim (1859-1936), an Austrian-Jewish feminist and the founder of the Jüdischer Frauenbund, treated by Breuer for severe cough, paralysis of the extremities on the right side of her body, and disturbances of vision, hearing, and speech, as well as hallucination and loss of consciousness. She was diagnosed with hysteria. Freud implies that her illness was a result of the grief felt over her father's real and physical illness that later led to his death[1].
Her treatment is regarded as marking the beginning of psychoanalysis. Breuer observed that whilst she experienced 'absences' (a change of personality accompanied by confusion), she would mutter words or phrases to herself. In inducing her to a state of hypnosis, Breuer found that these words were "profoundly melancholy phantasies...sometimes characterized by poetic beauty". Free Association came into being after Anna/Bertha decided (with Breuer's input) to end her hypnosis sessions and merely talk to Breuer, saying anything that came into her mind. She called this method of communication "chimney sweeping", and this served as the beginning of free association.
Anna's/Bertha's case also shed light for the first time on the phenomenon called transference, where the patient's feelings toward a significant figure in his/her life are redirected onto the therapist. By transference, Anna imagined to be pregnant with the doctor's baby. She experienced nausea and all the pregnancy symptoms. After this incident, Breuer stopped treating her.
Historical records since showed that when Breuer stopped treating Anna O. she was not becoming better but progressively worse[2]. In fact she was ultimately institutionalised: "Breuer told Freud that she was deranged; he hoped she would die to end her suffering"[3].
She later recovered over time and led a productive life: the West German government issued a postage stamp in honour of her contributions to the field of social work[4].
According to current research, "examination of the neurological details suggests that Anna suffered from complex partial seizures exacerbated by drug dependence."[5] In other words, her illness was not, as Freud suggested, psychological, but neurological. Many believe that Freud misdiagnosed her, and she in fact suffered from temporal lobe epilepsy, and many of her symptoms, including imagined smells, are common symptoms of types of epilepsy. [6]
Pappenheim under her real name translated the diary of her ancestor Gluckel of Hameln. | https://www.wikidoc.org/index.php/Anna_O. | |
8587d184beb6616258252f66c9790fd90f79352e | wikidoc | Annelid | Annelid
The annelids, collectively called Annelida (from Latin anellus "little ring"), are a large phylum of animals comprising the segmented worms, with about 15,000 modern species including the well-known earthworms and leeches. They are found in most wet environments, and include many terrestrial, freshwater, and especially marine species (such as the polychaetes), as well as some which are parasitic or mutualistic. They range in length from under a millimeter to over 3 meters (the seep tube worm Lamellibrachia luymesi).
# Physiology
Annelids are bilaterally symmetric and triploblastic protostomes with a coelom (which makes them coelomates), closed circulatory system and true segmentation. Their segmented bodies and coelom have given them evolutionary advantages over other worms. Oligochaetes and polychaetes typically have spacious coeloms; in leeches, the coelom is filled in with tissue and reduced to a system of narrow canals; archiannelids may lack the coelom entirely. The coelom is divided into a sequence of compartments by walls called septa. In the most general forms each compartment corresponds to a triple segment of the body, which also includes a portion of the nervous and (closed) circulatory systems, allowing it to function relatively independently. The closed circulatory system consists of networks of vessels containing blood with oxygen-carrying hemoglobin. Dorsal and ventral vessels are connected by segmental pairs of vessels. The dorsal vessel and five pairs of vessels that circle the esophagus of an earthworm are muscular and pump blood through the circulatory system. Tiny blood vessels are abundant in the earthworm's skin, which function as its respiratory organ. Each segment (metamere) is marked externally by one or more rings, called annuli. Each segment also has an outer layer of circular muscle underneath a thin cuticle and epidermis, and a system of longitudinal muscles. In earthworms and in daria the longitudinal muscles are strengthened by collagenous lamellae; the leeches have a double layer of muscles between the outer circulars and inner longitudinals. In most forms they also carry a varying number of bristles, called setae, and among the polychaetes a pair of appendages, called parapodia.
Anterior to the true segments lies the prostomium and peristomium, which carries the mouth, and posterior to them lies the pygidium, where the anus is located. The digestive tract is quite variable but is usually specialized. For example, in some groups (notably most earthworms) it has a typhlosole (to increase surface area) along much of its length. Different species of annelids have a wide variety of diets, including active and passive hunters, scavengers, filter feeders, direct deposit feeders which simply ingest the sediments, and blood-suckers. Annelids can also grow up to six inches.
The vascular system and the nervous system are separate from the digestive tract. The vascular system includes a dorsal vessel conveying the blood toward the front of the worm, and a ventral longitudinal vessel which conveys the blood in the opposite direction. The two systems are connected by a vascular sinus and by lateral vessels of various kinds, including in the true earthworms, capillaries on the body wall.
The nervous system has a nerve cord from which lateral nerves come in contact with each segment. Every segment has an autonomy; however, they unite to perform as a single body for functions such as locomotion. Growth in many groups occurs by replication of individual segmental units, in others the number of segments is fixed in early development.
Depending upon the species, annelids can reproduce both sexually and asexually.
## Asexual reproduction
Asexual reproduction by fission is a method used by some annelids and allows them to reproduce quickly. The posterior part of the body breaks off and forms a new identical worm. The position of the break is usually determined by an epidermal growth. Lumbriculus and Aulophorus, for example, are known to reproduce by the penis breaking into such fragments. This complete regeneration is noteworthy as these Annelid species are the most highly organized animals to have this capability. Many other taxa (such as most earthworms) cannot reproduce this way, though they have varying abilities to regrow amputated segments.
## Sexual reproduction
Sexual reproduction allows a species to better adapt to its environment. Some annelida species are hermaphroditic, while others have distinct sexes.
Most polychaete worms are gonochoristic, that is, they have separate males and females and external fertilization. The earliest larval stage, which is lost in some groups, is a ciliated trochophore, similar to those found in other phyla. The animal then begins to develop its segments, one after another, until it reaches its adult size.
Earthworms and other oligochaetes, as well as the leeches, are hermaphroditic and mate periodically throughout the year in favored environmental conditions. They mate by copulation. Two worms which are attracted by each other's secretions lay their bodies together with their heads pointing opposite directions. The fluid is transferred from the male pore to the other worm. Different methods of sperm transference have been observed in different genera, and may involve internal spermathecae (sperm storing chambers) or spermatophores that are attached to the outside of the other worm's body. The clitella lack the free-living ciliated trochophore larvae present in the polychaetes, the embryonic worms developing in a fluid-filled "cocoon" secreted by the clitellum.
# Fossil record
The annelid fossil record is sparse, but a few definite forms are known as early as the Cambrian, and there are some signs they were around in the earlier Precambrian, but the earliest unequivocal annelid fossils are only known from the former. Because the creatures have soft bodies, fossilization of a body is an especially rare event. However, a few annelids, such as the living polychaetes in the Serpulidae, secrete calcareous tubes, and such tubes are fairly common as fossils (although these are not necessarily from annelida, as other animal phyla can also secrete tubes). The hard jaws of certain polychaetes, known as scolecodonts, are known from the Ordovician onward, and are common enough to be used for stratigraphic correlation in some cases. The best-preserved and oldest annelid body fossils come from the Cambrian Lagerstätten such as the Burgess Shale of Canada, and the Middle Cambrian strata of the House Range in Utah. The Annelids are also diversely represented in the Pennsylvanian-age Mazon Creek fauna of Illinois. A few small groups have been treated as separate phyla: the Pogonophora and Vestimentifera, now included in the family Siboglinidae, and the Echiura.
# Relationships
The arthropods and their kin have long been considered the closest relatives of the annelids, on account of their common segmented structure, giving rise to the grouping of Articulata. However, a number of differences between the two groups suggest this may be convergent evolution. The other major phylum which is of definite relation to the annelids are the molluscs, which share with them the presence of trochophore larvae. Annelids and Molluscs are thus united as the Trochozoa, a taxon more strongly supported by molecular evidence.
Sipuncula, Echiura and Siboglinidae have traditionally been placed in their own phyla, while Clitellata has been considered separated from the polychaete annelids. But recent research indicates that all of them actually belongs within the Polychaete, even if some of these groups have lost their segmentation.
## Classes and subclasses of Annelida
- Clitellata
Oligochaeta - The class Oligochaeta includes the megadriles (earthworms), which are both aquatic and terrestrial, and the microdrile families such as tubificids, which include many marine members as well.
Leeches (Hirudinea) - These include both bloodsucking external parasites and predators of small invertebrates.
- Oligochaeta - The class Oligochaeta includes the megadriles (earthworms), which are both aquatic and terrestrial, and the microdrile families such as tubificids, which include many marine members as well.
- Leeches (Hirudinea) - These include both bloodsucking external parasites and predators of small invertebrates.
- Aphanoneura
- Polychaeta - This is the largest group of annelids and the majority are marine. All segments are identical each with a pair of parapodia. The parapodia are used for swimming, burrowing and the creation of a feeding current. | Annelid
The annelids, collectively called Annelida (from Latin anellus "little ring"), are a large phylum of animals comprising the segmented worms, with about 15,000 modern species including the well-known earthworms and leeches. They are found in most wet environments, and include many terrestrial, freshwater, and especially marine species (such as the polychaetes), as well as some which are parasitic or mutualistic. They range in length from under a millimeter to over 3 meters (the seep tube worm Lamellibrachia luymesi).
# Physiology
Annelids are bilaterally symmetric and triploblastic protostomes with a coelom (which makes them coelomates), closed circulatory system and true segmentation. Their segmented bodies and coelom have given them evolutionary advantages over other worms. Oligochaetes and polychaetes typically have spacious coeloms; in leeches, the coelom is filled in with tissue and reduced to a system of narrow canals; archiannelids may lack the coelom entirely. The coelom is divided into a sequence of compartments by walls called septa. In the most general forms each compartment corresponds to a triple segment of the body, which also includes a portion of the nervous and (closed) circulatory systems, allowing it to function relatively independently. The closed circulatory system consists of networks of vessels containing blood with oxygen-carrying hemoglobin. Dorsal and ventral vessels are connected by segmental pairs of vessels. The dorsal vessel and five pairs of vessels that circle the esophagus of an earthworm are muscular and pump blood through the circulatory system. Tiny blood vessels are abundant in the earthworm's skin, which function as its respiratory organ. Each segment (metamere) is marked externally by one or more rings, called annuli. Each segment also has an outer layer of circular muscle underneath a thin cuticle and epidermis, and a system of longitudinal muscles. In earthworms and in daria the longitudinal muscles are strengthened by collagenous lamellae; the leeches have a double layer of muscles between the outer circulars and inner longitudinals. In most forms they also carry a varying number of bristles, called setae, and among the polychaetes a pair of appendages, called parapodia.
Anterior to the true segments lies the prostomium and peristomium, which carries the mouth, and posterior to them lies the pygidium, where the anus is located. The digestive tract is quite variable but is usually specialized. For example, in some groups (notably most earthworms) it has a typhlosole (to increase surface area) along much of its length. Different species of annelids have a wide variety of diets, including active and passive hunters, scavengers, filter feeders, direct deposit feeders which simply ingest the sediments, and blood-suckers. Annelids can also grow up to six inches.
The vascular system and the nervous system are separate from the digestive tract. The vascular system includes a dorsal vessel conveying the blood toward the front of the worm, and a ventral longitudinal vessel which conveys the blood in the opposite direction. The two systems are connected by a vascular sinus and by lateral vessels of various kinds, including in the true earthworms, capillaries on the body wall.
The nervous system has a nerve cord from which lateral nerves come in contact with each segment. Every segment has an autonomy; however, they unite to perform as a single body for functions such as locomotion. Growth in many groups occurs by replication of individual segmental units, in others the number of segments is fixed in early development.
Depending upon the species, annelids can reproduce both sexually and asexually.
## Asexual reproduction
Asexual reproduction by fission is a method used by some annelids and allows them to reproduce quickly. The posterior part of the body breaks off and forms a new identical worm. The position of the break is usually determined by an epidermal growth. Lumbriculus and Aulophorus, for example, are known to reproduce by the penis breaking into such fragments. This complete regeneration is noteworthy as these Annelid species are the most highly organized animals to have this capability.[1] Many other taxa (such as most earthworms) cannot reproduce this way, though they have varying abilities to regrow amputated segments.
## Sexual reproduction
Sexual reproduction allows a species to better adapt to its environment. Some annelida species are hermaphroditic, while others have distinct sexes.
Most polychaete worms are gonochoristic, that is, they have separate males and females and external fertilization. The earliest larval stage, which is lost in some groups, is a ciliated trochophore, similar to those found in other phyla. The animal then begins to develop its segments, one after another, until it reaches its adult size.
Earthworms and other oligochaetes, as well as the leeches, are hermaphroditic and mate periodically throughout the year in favored environmental conditions. They mate by copulation. Two worms which are attracted by each other's secretions lay their bodies together with their heads pointing opposite directions. The fluid is transferred from the male pore to the other worm. Different methods of sperm transference have been observed in different genera, and may involve internal spermathecae (sperm storing chambers) or spermatophores that are attached to the outside of the other worm's body. The clitella lack the free-living ciliated trochophore larvae present in the polychaetes, the embryonic worms developing in a fluid-filled "cocoon" secreted by the clitellum.
# Fossil record
The annelid fossil record is sparse, but a few definite forms are known as early as the Cambrian, and there are some signs they were around in the earlier Precambrian, but the earliest unequivocal annelid fossils are only known from the former. Because the creatures have soft bodies, fossilization of a body is an especially rare event. However, a few annelids, such as the living polychaetes in the Serpulidae, secrete calcareous tubes, and such tubes are fairly common as fossils (although these are not necessarily from annelida, as other animal phyla can also secrete tubes). The hard jaws of certain polychaetes, known as scolecodonts, are known from the Ordovician onward, and are common enough to be used for stratigraphic correlation in some cases. The best-preserved and oldest annelid body fossils come from the Cambrian Lagerstätten such as the Burgess Shale of Canada, and the Middle Cambrian strata of the House Range in Utah. The Annelids are also diversely represented in the Pennsylvanian-age Mazon Creek fauna of Illinois. A few small groups have been treated as separate phyla: the Pogonophora and Vestimentifera, now included in the family Siboglinidae, and the Echiura.
# Relationships
The arthropods and their kin have long been considered the closest relatives of the annelids, on account of their common segmented structure, giving rise to the grouping of Articulata. However, a number of differences between the two groups suggest this may be convergent evolution. The other major phylum which is of definite relation to the annelids are the molluscs, which share with them the presence of trochophore larvae. Annelids and Molluscs are thus united as the Trochozoa, a taxon more strongly supported by molecular evidence.
Sipuncula, Echiura and Siboglinidae have traditionally been placed in their own phyla, while Clitellata has been considered separated from the polychaete annelids. But recent research indicates that all of them actually belongs within the Polychaete, even if some of these groups have lost their segmentation[1].
## Classes and subclasses of Annelida
- Clitellata
Oligochaeta - The class Oligochaeta includes the megadriles (earthworms), which are both aquatic and terrestrial, and the microdrile families such as tubificids, which include many marine members as well.
Leeches (Hirudinea) - These include both bloodsucking external parasites and predators of small invertebrates.
- Oligochaeta - The class Oligochaeta includes the megadriles (earthworms), which are both aquatic and terrestrial, and the microdrile families such as tubificids, which include many marine members as well.
- Leeches (Hirudinea) - These include both bloodsucking external parasites and predators of small invertebrates.
- Aphanoneura
- Polychaeta - This is the largest group of annelids and the majority are marine. All segments are identical each with a pair of parapodia. The parapodia are used for swimming, burrowing and the creation of a feeding current. | https://www.wikidoc.org/index.php/Annelid | |
bc89f9e24687fbe7808400185c34247473ec2ccf | wikidoc | Anoikis | Anoikis
Anoikis (Greek: homelessness) is a form of apoptosis which is induced by anchorage-dependent cells detaching from the surrounding extracellular matrix (ECM). Usually cells stay close to the tissue to which they belong since the communication between proximal cells as well as between cells and ECM provide essential signals for growth or survival. When cells are detached from the ECM, i.e. there is a loss of normal cell-matrix interactions, they may undergo anoikis. However, metastatic tumor cells may escape from anoikis and invade other organs.
# Anoikis in metastasis
The mechanism by which invading tumor cells survive the anoikis process remains largely unknown. Recent findings suggest that the protein TrkB, best known for its role in the nervous system, might be involved together with its ligand, brain-derived neurotrophic factor (BDNF). It seems that TrkB could make tumor cells resistant to anoikis by activating phosphatidylinositol 3-kinase (PI3K) signaling cascade.
In squamous cell carcinoma, researchers have found that anoikis resistance can be induced through hepatocyte growth factor (HGF) activating BOTH extracellular signalling-receptor kinase (ERK) and PI3K. | Anoikis
Anoikis (Greek: homelessness) is a form of apoptosis which is induced by anchorage-dependent cells detaching from the surrounding extracellular matrix (ECM)[1]. Usually cells stay close to the tissue to which they belong since the communication between proximal cells as well as between cells and ECM provide essential signals for growth or survival. When cells are detached from the ECM, i.e. there is a loss of normal cell-matrix interactions, they may undergo anoikis. However, metastatic tumor cells may escape from anoikis and invade other organs.
# Anoikis in metastasis
The mechanism by which invading tumor cells survive the anoikis process remains largely unknown. Recent findings suggest that the protein TrkB, best known for its role in the nervous system, might be involved together with its ligand, brain-derived neurotrophic factor (BDNF). It seems that TrkB could make tumor cells resistant to anoikis by activating phosphatidylinositol 3-kinase (PI3K) signaling cascade.
In squamous cell carcinoma, researchers have found that anoikis resistance can be induced through hepatocyte growth factor (HGF) activating BOTH extracellular signalling-receptor kinase (ERK) and PI3K. | https://www.wikidoc.org/index.php/Anoikis | |
cb115c2c2653524e38941acc7701e6a331ed8943 | wikidoc | Cestoda | Cestoda
Cestoda is the class of parasitic flatworms, commonly called tapeworms, that live in the digestive tract of vertebrates as adults and often in the bodies of various animals as juveniles.
# Overview
Authors Craig and Ito, in Intestinal Cestodes describe the gut-dwelling worm as a segmented, band like (Cestoda) in its adult stage (Craig & Ito 2007:524). What occurs in tissues and organs of vertebrates or humans, is the growth of a cyst-like juvenile or metacestode stage. The potential cause of illnesses and diseases is due to the metacestode stages happening in human tissues rather than the adult tapeworm (Craig and Ito 2007:524).
The tegument is the body surface of the adult tapeworm and due to this the tapeworms take the host nutrients and not attack the mucosa of the small intestine, or remove blood, hence infections are instead benevolent and most often don't show any signs of illness (Craig & Ito 2007:524). A carrier can notice the segments (proglottides) when using the bathroom for instance in the feces in a toilet bowl, around a latrine or frequently because the tapeworms are moving around constantly one may find it in the under-garments (Craig and Ito 2007: 524).
# Life cycle
The life cycle of a tape worm starts out with an animal eating undercooked, infected meat. The tape worm will then grow, and release small packages with fertilized eggs and sperm. These packages are excreted out of the body. If they happen to, for example, get on grass, the package will open and by that time, the tape worm eggs will have developed. The eggs are released on to the grass, if a cow eats that grass, the eggs will become larva and burrow into the cow's muscle. And if that cow would be turned into meat and if any of that meat is undercooked, the whole cycle starts again.
## Scolex
The Scolex or "head" of the worm attaches to the intestine of the definitive host. In some groups, the scolex is dominated by bothria, which are sometimes called "sucking grooves", and function like suction cups. Other groups have hooks and suckers that aid in attachment. Cyclophyllid cestodes can be identified by the presence of four suckers on their scolex, though they may have other structures.
While the scolex is often the most distinctive part of an adult tapeworm, it is often unnoticed in a clinical setting as it is inside the patient. Thus, identifying eggs and proglottids in feces is important.
## Muscular system
The main nerve center of cestode is in scolex, motor and sensory innervation depends on number and complexity of scolex. Smaller nerves emanate from the commissures to supply the general body muscular and sensory ending.1 The cirrus and vagina are innervated and sensory endings around the genital pore are more plentiful than other areas. Sensory function includes both tactoreception and chemoreception.1
## Proglottids
The body is composed of successive units posterior to the scolex, the proglottids. The sum of the proglottids is called a strobila, which is thin, resembling a strip of tape, and is the source of the common name tapeworm. Like some other flatworms, cestodes use flame cells (protonephridia) for excretion, which are located in the proglottids.
Mature or gravid proglottids are released from the mature tapeworm and leave the host in its feces.
Because each proglottid contains the male and female reproductive structures, they can reproduce independently. It has been suggested by some biologists that each should be considered a single organism, and that the tapeworm is actually a colony of proglottids.
# Pathology
According to Intestinal Cestodes, authors Craig, and Ito 2007 suggest that the effects of this gut dwelling Cestodes are usually very minimal. The people that have been infected by this tapeworm have described the following symptoms: abdominal discomfort and pain, cramp, colic, flatulence, diarrhea, constipation, nausea, dizziness, vomiting, restlessness, vertigo, headache, tiredness, malabsorption, anorexia, muscular pain, vitamin deficiency, megaloblastic anemia, weight loss (or gain), intestinal blockage, jejunal perforation, appendicitis, pancreatitis, pseudo-incontinence, pruritis ani, rectal-flutters, spontaneous voiding of segments from the anus, depression and psychosis (Craig & Ito 2007:524). Furthermore, through self-infection of Taenia Solium (the pork tapeworm) there has been in the past a serious life threatening infections of taeniais (also referred to as taeniosis) which may make the chances of neurocysticercosis go higher (Craig & Ito 2007: 524). | Cestoda
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Cestoda is the class of parasitic flatworms, commonly called tapeworms, that live in the digestive tract of vertebrates as adults and often in the bodies of various animals as juveniles.
# Overview
Authors Craig and Ito, in Intestinal Cestodes describe the gut-dwelling worm as a segmented, band like (Cestoda) in its adult stage (Craig & Ito 2007:524). What occurs in tissues and organs of vertebrates or humans, is the growth of a cyst-like juvenile or metacestode stage. The potential cause of illnesses and diseases is due to the metacestode stages happening in human tissues rather than the adult tapeworm (Craig and Ito 2007:524).
The tegument is the body surface of the adult tapeworm and due to this the tapeworms take the host nutrients and not attack the mucosa of the small intestine, or remove blood, hence infections are instead benevolent and most often don't show any signs of illness (Craig & Ito 2007:524). A carrier can notice the segments (proglottides) when using the bathroom for instance in the feces in a toilet bowl, around a latrine or frequently because the tapeworms are moving around constantly one may find it in the under-garments (Craig and Ito 2007: 524).
# Life cycle
The life cycle of a tape worm starts out with an animal eating undercooked, infected meat. The tape worm will then grow, and release small packages with fertilized eggs and sperm. These packages are excreted out of the body. If they happen to, for example, get on grass, the package will open and by that time, the tape worm eggs will have developed. The eggs are released on to the grass, if a cow eats that grass, the eggs will become larva and burrow into the cow's muscle. And if that cow would be turned into meat and if any of that meat is undercooked, the whole cycle starts again.
## Scolex
The Scolex or "head" of the worm attaches to the intestine of the definitive host. In some groups, the scolex is dominated by bothria, which are sometimes called "sucking grooves", and function like suction cups. Other groups have hooks and suckers that aid in attachment. Cyclophyllid cestodes can be identified by the presence of four suckers on their scolex, though they may have other structures.
While the scolex is often the most distinctive part of an adult tapeworm, it is often unnoticed in a clinical setting as it is inside the patient. Thus, identifying eggs and proglottids in feces is important.
## Muscular system
The main nerve center of cestode is in scolex, motor and sensory innervation depends on number and complexity of scolex. Smaller nerves emanate from the commissures to supply the general body muscular and sensory ending.1 The cirrus and vagina are innervated and sensory endings around the genital pore are more plentiful than other areas. Sensory function includes both tactoreception and chemoreception.1
## Proglottids
The body is composed of successive units posterior to the scolex, the proglottids. The sum of the proglottids is called a strobila, which is thin, resembling a strip of tape, and is the source of the common name tapeworm. Like some other flatworms, cestodes use flame cells (protonephridia) for excretion, which are located in the proglottids.
Mature or gravid proglottids are released from the mature tapeworm and leave the host in its feces.
Because each proglottid contains the male and female reproductive structures, they can reproduce independently. It has been suggested by some biologists that each should be considered a single organism, and that the tapeworm is actually a colony of proglottids.
# Pathology
According to Intestinal Cestodes, authors Craig, and Ito 2007 suggest that the effects of this gut dwelling Cestodes are usually very minimal. The people that have been infected by this tapeworm have described the following symptoms: abdominal discomfort and pain, cramp, colic, flatulence, diarrhea, constipation, nausea, dizziness, vomiting, restlessness, vertigo, headache, tiredness, malabsorption, anorexia, muscular pain, vitamin deficiency, megaloblastic anemia, weight loss (or gain), intestinal blockage, jejunal perforation, appendicitis, pancreatitis, pseudo-incontinence, pruritis ani, rectal-flutters, spontaneous voiding of segments from the anus, depression and psychosis (Craig & Ito 2007:524). Furthermore, through self-infection of Taenia Solium (the pork tapeworm) there has been in the past a serious life threatening infections of taeniais (also referred to as taeniosis) which may make the chances of neurocysticercosis go higher (Craig & Ito 2007: 524). | https://www.wikidoc.org/index.php/Anticestodals | |
50f2564e4776ab85d89cea1787bad525e868654c | wikidoc | Antigen | Antigen
# Overview
An antigen (from antibody-generating) or immunogen is a molecule that sometimes stimulates an immune response. The word originated from the notion that they can stimulate antibody generation. We now know that the immune system does not consist of only antibodies. The modern definition encompasses all substances that can be recognized by the adaptive immune system.
Antigens are usually proteins or polysaccharides. This includes parts (coats, capsules, cell walls, flagella, fimbrae, and toxins) of bacteria, viruses, and other microorganisms. Lipids and nucleic acids are antigenic only when combined with proteins and polysaccharides. Non-microbial exogenous (non-self) antigens can include pollen, egg white, and proteins from transplanted tissues and organs or on the surface of transfused blood cells.
- Tolerogen - An antigen that invokes a specific immune non-responsiveness due to its molecular form. If its molecular form is changed, a tolerogen can become an immunogen.
- Allergen - An allergen is a substance that causes the allergic reaction. The (detrimental) reaction may result after exposure via ingestion, inhalation, injection, or contact with skin.
Cells present their antigens to the immune system via a histocompatibility molecule. Depending on the antigen presented and the type of the histocompatibility molecule, several types of immune cells can become activated.
# Origin of antigens
Antigens can be classified in order of their origins.
## Exogenous antigens
Exogenous antigens are antigens that have entered the body from the outside, for example by inhalation, ingestion, or injection. By endocytosis or phagocytosis, these antigens are taken into the antigen-presenting cells (APCs) and processed into fragments. APCs then present the fragments to T helper cells (CD4+) by the use of class II histocompatibility molecules on their surface. Some T cells are specific for the peptide:MHC complex. They become activated and start to secrete cytokines. Cytokines are substances that can activate cytotoxic T lymphocytes (CTL), antibody-secreting B cells, macrophages, and other particles.
## Endogenous antigens
Endogenous antigens are antigens that have been generated within the cell, as a result of normal cell metabolism, or because of viral or intracellular bacterial infection. The fragments are then presented on the cell surface in the complex with MHC class I molecules. If activated cytotoxic CD8+ T cells recognize them, the T cells begin to secrete various toxins that cause the lysis or apoptosis of the infected cell. In order to keep the cytotoxic cells from killing cells just for presenting self-proteins, self-reactive T cells are deleted from the repertoire as a result of tolerance (also known as negative selection, which occurs in the gametes of a cow.
## Autoantigens
An autoantigen is usually a normal protein or complex of proteins (and sometimes DNA or RNA) that is recognized by the immune system of patients suffering from a specific autoimmune disease. These antigens should, under normal conditions, not be the target of the immune system, but, due to mainly genetic and environmental factors, the normal immunological tolerance for such an antigen has been lost in these patients.
# Tumor antigens
Tumor antigens or Neoantigens are those antigens that are presented by MHC I or MHC II molecules on the surface of tumor cells. These antigens can sometimes be presented by tumor cells and never by the normal ones. In this case, they are called tumor-specific antigens (TSAs) and, in general, result from a tumor-specific mutation. More common are antigens that are presented by tumor cells and normal cells, and they are called tumor-associated antigens (TAAs). Cytotoxic T lymphocytes that recognize these antigens may be able to destroy the tumor cells before they proliferate or metastasize.
Tumor antigens can also be on the surface of the tumor in the form of, for example, a mutated receptor, in which case they will be recognized by B cells.
# Nativity
A native antigen is an antigen which isn't yet processed by an APC to smaller parts. T cells cannot bind native antigens, but require that they are processed by APCs, while B cells can be activated by native ones. | Antigen
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
An antigen (from antibody-generating) or immunogen is a molecule that sometimes stimulates an immune response. The word originated from the notion that they can stimulate antibody generation. We now know that the immune system does not consist of only antibodies. The modern definition encompasses all substances that can be recognized by the adaptive immune system.
Antigens are usually proteins or polysaccharides. This includes parts (coats, capsules, cell walls, flagella, fimbrae, and toxins) of bacteria, viruses, and other microorganisms. Lipids and nucleic acids are antigenic only when combined with proteins and polysaccharides. Non-microbial exogenous (non-self) antigens can include pollen, egg white, and proteins from transplanted tissues and organs or on the surface of transfused blood cells.
- Tolerogen - An antigen that invokes a specific immune non-responsiveness due to its molecular form. If its molecular form is changed, a tolerogen can become an immunogen.
- Allergen - An allergen is a substance that causes the allergic reaction. The (detrimental) reaction may result after exposure via ingestion, inhalation, injection, or contact with skin.
Cells present their antigens to the immune system via a histocompatibility molecule. Depending on the antigen presented and the type of the histocompatibility molecule, several types of immune cells can become activated.
# Origin of antigens
Antigens can be classified in order of their origins.
## Exogenous antigens
Exogenous antigens are antigens that have entered the body from the outside, for example by inhalation, ingestion, or injection. By endocytosis or phagocytosis, these antigens are taken into the antigen-presenting cells (APCs) and processed into fragments. APCs then present the fragments to T helper cells (CD4+) by the use of class II histocompatibility molecules[2] on their surface. Some T cells are specific for the peptide:MHC complex. They become activated and start to secrete cytokines. Cytokines are substances that can activate cytotoxic T lymphocytes (CTL), antibody-secreting B cells, macrophages, and other particles.
## Endogenous antigens
Endogenous antigens are antigens that have been generated within the cell, as a result of normal cell metabolism, or because of viral or intracellular bacterial infection. The fragments are then presented on the cell surface in the complex with MHC class I molecules. If activated cytotoxic CD8+ T cells recognize them, the T cells begin to secrete various toxins that cause the lysis or apoptosis of the infected cell. In order to keep the cytotoxic cells from killing cells just for presenting self-proteins, self-reactive T cells are deleted from the repertoire as a result of tolerance (also known as negative selection, which occurs in the gametes of a cow.
## Autoantigens
An autoantigen is usually a normal protein or complex of proteins (and sometimes DNA or RNA) that is recognized by the immune system of patients suffering from a specific autoimmune disease. These antigens should, under normal conditions, not be the target of the immune system, but, due to mainly genetic and environmental factors, the normal immunological tolerance for such an antigen has been lost in these patients.
# Tumor antigens
Tumor antigens or Neoantigens are those antigens that are presented by MHC I or MHC II molecules on the surface of tumor cells. These antigens can sometimes be presented by tumor cells and never by the normal ones. In this case, they are called tumor-specific antigens (TSAs) and, in general, result from a tumor-specific mutation. More common are antigens that are presented by tumor cells and normal cells, and they are called tumor-associated antigens (TAAs). Cytotoxic T lymphocytes that recognize these antigens may be able to destroy the tumor cells before they proliferate or metastasize.
Tumor antigens can also be on the surface of the tumor in the form of, for example, a mutated receptor, in which case they will be recognized by B cells.
# Nativity
A native antigen is an antigen which isn't yet processed by an APC to smaller parts. T cells cannot bind native antigens, but require that they are processed by APCs, while B cells can be activated by native ones. | https://www.wikidoc.org/index.php/Antigen | |
9d769447de840c0f909693db3dc7cdab79840942 | wikidoc | Aphakia | Aphakia
Aphakia is the absence of the lens of the eye, due to surgical removal, a perforating wound or ulcer, or congenital anomaly. It causes a loss of accommodation, hyperopia, and a deep anterior chamber. Complications include detachment of the vitreous or retina, and glaucoma.
Aphakic people are reported to be able to see ultraviolet wavelengths that are normally excluded by the lens. This may have had an effect on the colors perceived by artist Claude Monet, who had cataract surgery in 1923.
# Treatment
Aphakia could be corrected by wearing glasses, contact lenses or by implant of an artificial lens (pseudo-phakia). | Aphakia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Aphakia is the absence of the lens of the eye, due to surgical removal, a perforating wound or ulcer, or congenital anomaly. It causes a loss of accommodation, hyperopia, and a deep anterior chamber. Complications include detachment of the vitreous or retina, and glaucoma.
Aphakic people are reported to be able to see ultraviolet wavelengths that are normally excluded by the lens.[1] This may have had an effect on the colors perceived by artist Claude Monet, who had cataract surgery in 1923.
# Treatment
Aphakia could be corrected by wearing glasses, contact lenses or by implant of an artificial lens (pseudo-phakia). | https://www.wikidoc.org/index.php/Aphakia | |
19e586b484de8be519023e0ae9f5fab50bb734e8 | wikidoc | Insulin | Insulin
Insulin (from Latin insula, island) is a peptide hormone produced by beta cells of the pancreatic islets; it is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of carbohydrates, especially glucose from the blood into liver, fat and skeletal muscle cells. In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both. Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat.
Beta cells are sensitive to glucose concentrations, also known as blood sugar levels. When the glucose level is high, the beta cells secrete insulin into the blood; when glucose levels are low, secretion of insulin is inhibited. Their neighboring alpha cells, by taking their cues from the beta cells, secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high. Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin. The secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism of glucose homeostasis.
If beta cells are destroyed by an autoimmune reaction, insulin can no longer be synthesized or be secreted into the blood. This results in type 1 diabetes mellitus, which is characterized by abnormally high blood glucose concentrations, and generalized body wasting. In type 2 diabetes mellitus the destruction of beta cells is less pronounced than in type 1 diabetes, and is not due to an autoimmune process. Instead there is an accumulation of amyloid in the pancreatic islets, which likely disrupts their anatomy and physiology. The pathogenesis of type 2 diabetes is not well understood but patients exhibit a reduced population of islet beta-cells, reduced secretory function of islet beta-cells that survive, and peripheral tissue insulin resistance. Type 2 diabetes is characterized by high rates of glucagon secretion into the blood which are unaffected by, and unresponsive to the concentration of glucose in the blood. Insulin is still secreted into the blood in response to the blood glucose. As a result, the insulin levels, even when the blood sugar level is normal, are much higher than they are in healthy persons.
The human insulin protein is composed of 51 amino acids, and has a molecular mass of 5808 Da. It is a dimer of an A-chain and a B-chain, which are linked together by disulfide bonds. Insulin's structure varies slightly between species of animals. Insulin from animal sources differs somewhat in effectiveness (in carbohydrate metabolism effects) from human insulin because of these variations. Porcine insulin is especially close to the human version, and was widely used to treat type 1 diabetics before human insulin could be produced in large quantities by recombinant DNA technologies.
The crystal structure of insulin in the solid state was determined by Dorothy Hodgkin. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.
# Evolution and species distribution
Insulin may have originated more than a billion years ago. The molecular origins of insulin go at least as far back as the simplest unicellular eukaryotes. Apart from animals, insulin-like proteins are also known to exist in the Fungi and Protista kingdoms.
Insulin is produced by beta cells of the pancreatic islets in most vertebrates and by the Brockmann body in some teleost fish. Cone snails Conus geographus and Conus tulipa, venomous sea snails that hunt small fish, use modified forms of insulin in their venom cocktails. The insulin toxin, closer in structure to fishes' than to snails' native insulin, slows down the prey fishes by lowering their blood glucose levels.
# Gene
The preproinsulin precursor of insulin is encoded by the INS gene.
## Alleles
A variety of mutant alleles with changes in the coding region have been identified. A read-through gene, INS-IGF2, overlaps with this gene at the 5' region and with the IGF2 gene at the 3' region.
## Regulation
In the pancreatic β cells, glucose is the primary physiological stimulus for the regulation of insulin synthesis. Insulin is mainly regulated through the transcription factors PDX1, NeuroD1, and MafA.
PDX1 (Pancreatic and duodenal homeobox protein 1) is in the nuclear periphery upon low blood glucose levels interacting with corepressors HDAC1 and 2 which is downregulating the insulin secretion. An increase in blood glucose levels causes phosphorylation of PDX1 and it translocates centrally and binds the A3 element within the insulin promoter. Upon translocation it interacts with coactivators HAT p300 and acetyltransferase set 7/9. PDX1 affects the histone modifications through acetylation and deacetylation as well as methylation. It is also said to suppress glucagon.
NeuroD1, also known as β2, regulates insulin exocytosis in pancreatic β cells by directly inducing the expression of genes involved in exocytosis. It is localized in the cytosol, but in response to high glucose it becomes glycosylated by OGT and/or phosphorylated by ERK, which causes translocation to the nucleus. In the nucleus β2 heterodimerizes with E47, binds to the E1 element of the insulin promoter and recruits co-activator p300 which acetylates β2. It is able to interact with other transcription factors as well in activation of the insulin gene.
MafA is degraded by proteasomes upon low blood glucose levels. Increased levels of glucose make an unknown protein glycosylated. This protein works as a transcription factor for MafA in an unknown manner and MafA is transported out of the cell. MafA is then translocated back into the nucleus where it binds the C1 element of the insulin promoter.
These transcription factors work synergistically and in a complex arrangement. Increased blood glucose can after a while destroy the binding capacities of these proteins, and therefore reduce the amount of insulin secreted, causing diabetes. The decreased binding activities can be mediated by glucose induced oxidative stress and antioxidants are said to prevent the decreased insulin secretion in glucotoxic pancreatic β cells. Stress signalling molecules and reactive oxygen species inhibits the insulin gene by interfering with the cofactors binding the transcription factors and the transcription factors it self.
Several regulatory sequences in the promoter region of the human insulin gene bind to transcription factors. In general, the A-boxes bind to Pdx1 factors, E-boxes bind to NeuroD, C-boxes bind to MafA, and cAMP response elements to CREB. There are also silencers that inhibit transcription.
# Protein structure
Within vertebrates, the amino acid sequence of insulin is strongly conserved. Bovine insulin differs from human in only three amino acid residues, and porcine insulin in one. Even insulin from some species of fish is similar enough to human to be clinically effective in humans. Insulin in some invertebrates is quite similar in sequence to human insulin, and has similar physiological effects. The strong homology seen in the insulin sequence of diverse species suggests that it has been conserved across much of animal evolutionary history. The C-peptide of proinsulin (discussed later), however, differs much more among species; it is also a hormone, but a secondary one.
The primary structure of bovine insulin was first determined by Frederick Sanger in 1951. After that, this polypeptide was synthesized independently by several groups. The 3-dimensional structure of insulin was determined by X-ray crystallography in Dorothy Hodgkin's laboratory in 1969 (PDB file 1ins).
Insulin is produced and stored in the body as a hexamer (a unit of six insulin molecules), while the active form is the monomer. The hexamer is an inactive form with long-term stability, which serves as a way to keep the highly reactive insulin protected, yet readily available. The hexamer-monomer conversion is one of the central aspects of insulin formulations for injection. The hexamer is far more stable than the monomer, which is desirable for practical reasons; however, the monomer is a much faster-reacting drug because diffusion rate is inversely related to particle size. A fast-reacting drug means insulin injections do not have to precede mealtimes by hours, which in turn gives people with diabetes more flexibility in their daily schedules. Insulin can aggregate and form fibrillar interdigitated beta-sheets. This can cause injection amyloidosis, and prevents the storage of insulin for long periods.
# Synthesis, physiological effects, and degradation
## Synthesis
Insulin is produced in the pancreas and the Brockmann body (in some fish), and released when any of several stimuli are detected. These stimuli include ingested protein and glucose in the blood produced from digested food. Carbohydrates can be polymers of simple sugars or the simple sugars themselves. If the carbohydrates include glucose, then that glucose will be absorbed into the bloodstream and blood glucose level will begin to rise. In target cells, insulin initiates a signal transduction, which has the effect of increasing glucose uptake and storage. Finally, insulin is degraded, terminating the response.
In mammals, insulin is synthesized in the pancreas within the beta cells. One million to three million pancreatic islets form the endocrine part of the pancreas, which is primarily an exocrine gland. The endocrine portion accounts for only 2% of the total mass of the pancreas. Within the pancreatic islets, beta cells constitute 65–80% of all the cells.
Insulin consists of two polypeptide chains, the A- and B- chains, linked together by disulfide bonds. It is however first synthesized as a single polypeptide called preproinsulin in beta cells. Preproinsulin contains a 24-residue signal peptide which directs the nascent polypeptide chain to the rough endoplasmic reticulum (RER). The signal peptide is cleaved as the polypeptide is translocated into lumen of the RER, forming proinsulin. In the RER the proinsulin folds into the correct conformation and 3 disulfide bonds are formed. About 5–10 min after its assembly in the endoplasmic reticulum, proinsulin is transported to the trans-Golgi network (TGN) where immature granules are formed. Transport to the TGN may take about 30 min.
Proinsulin undergoes maturation into active insulin through the action of cellular endopeptidases known as prohormone convertases (PC1 and PC2), as well as the exoprotease carboxypeptidase E. The endopeptidases cleave at 2 positions, releasing a fragment called the C-peptide, and leaving 2 peptide chains, the B- and A- chains, linked by 2 disulfide bonds. The cleavage sites are each located after a pair of basic residues (lysine-64 and arginine-65, and arginine-31 and −32). After cleavage of the C-peptide, these 2 pairs of basic residues are removed by the carboxypeptidase. The C-peptide is the central portion of proinsulin, and the primary sequence of proinsulin goes in the order "B-C-A" (the B and A chains were identified on the basis of mass and the C-peptide was discovered later).
The resulting mature insulin is packaged inside mature granules waiting for metabolic signals (such as leucine, arginine, glucose and mannose) and vagal nerve stimulation to be exocytosed from the cell into the circulation.
The endogenous production of insulin is regulated in several steps along the synthesis pathway:
- At transcription from the insulin gene
- In mRNA stability
- At the mRNA translation
- In the posttranslational modifications
Insulin and its related proteins have been shown to be produced inside the brain, and reduced levels of these proteins are linked to Alzheimer's disease.
Insulin release is stimulated also by beta-2 receptor stimulation and inhibited by alpha-1 receptor stimulation. In addition, cortisol, glucagon and growth hormone antagonize the actions of insulin during times of stress. Insulin also inhibits fatty acid release by hormone sensitive lipase in adipose tissue.
## Release
Beta cells in the islets of Langerhans release insulin in two phases. The first-phase release is rapidly triggered in response to increased blood glucose levels, and lasts about 10 minutes. The second phase is a sustained, slow release of newly formed vesicles triggered independently of sugar, peaking in 2 to 3 hours. Reduced first-phase insulin release may be the earliest detectable beta cell defect predicting onset of type 2 diabetes. First-phase release and insulin sensitivity are independent predictors of diabetes.
The description of first phase release is as follows:
- Glucose enters the β-cells through the glucose transporters, GLUT2. These glucose transporters have a relatively low affinity for glucose, ensuring that the rate of glucose entry into the β-cells is proportional to the extracellular glucose concentration (within the physiological range). At low blood sugar levels very little glucose enters the β-cells; at high blood glucose concentrations large quantities of glucose enter these cells.
- The glucose that enters the β-cell is phosphorylated to glucose-6-phosphate (G-6-P) by glucokinase (hexokinase IV) which is not inhibited by G-6-P in the way that the hexokinases in other tissues (hexokinase I – III) are affected by this product. This means that the intracellular G-6-P concentration remains proportional to the blood sugar concentration.
- Glucose-6-phosphate enters glycolytic pathway and then, via the pyruvate dehydrogenase reaction, into the Krebs cycle, where multiple, high-energy ATP molecules are produced by the oxidation of acetyl CoA (the Krebs cycle substrate), leading to a rise in the ATP:ADP ratio within the cell.
- An increased intracellular ATP:ADP ratio closes the ATP-sensitive SUR1/Kir6.2 potassium channel (see sulfonylurea receptor). This prevents potassium ions (K+) from leaving the cell by facilitated diffusion, leading to a buildup of intracellular potassium ions. As a result, the inside of the cell becomes less negative with respect to the outside, leading to the depolarization of the cell surface membrane.
- Upon depolarization, voltage-gated calcium ion (Ca2+) channels open, allowing calcium ions to move into the cell by facilitated diffusion.
- The cytosolic calcium ion concentration can also be increased by calcium release from intracellular stores via activation of ryanodine receptors.
- The calcium ion concentration in the cytosol of the beta cells can also, or additionally, be increased through the activation of phospholipase C resulting from the binding of an extracellular ligand (hormone or neurotransmitter) to a G protein-coupled membrane receptor. Phospholipase C cleaves the membrane phospholipid, phosphatidyl inositol 4,5-bisphosphate, into inositol 1,4,5-trisphosphate and diacylglycerol. Inositol 1,4,5-trisphosphate (IP3) then binds to receptor proteins in the plasma membrane of the endoplasmic reticulum (ER). This allows the release of Ca2+ ions from the ER via IP3-gated channels, which raises the cytosolic concentration of calcium ions independently of the effects of a high blood glucose concentration. Parasympathetic stimulation of the pancreatic islets operates via this pathway to increase insulin secretion into the blood.
- The significantly increased amount of calcium ions in the cells' cytoplasm causes the release into the blood of previously synthesized insulin, which has been stored in intracellular secretory vesicles.
This is the primary mechanism for release of insulin. Other substances known to stimulate insulin release include the amino acids arginine and leucine, parasympathetic release of acetylcholine (acting via the phospholipase C pathway), sulfonylurea, cholecystokinin (CCK, also via phospholipase C), and the gastrointestinally derived incretins, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP).
Release of insulin is strongly inhibited by norepinephrine (noradrenaline), which leads to increased blood glucose levels during stress. It appears that release of catecholamines by the sympathetic nervous system has conflicting influences on insulin release by beta cells, because insulin release is inhibited by α2-adrenergic receptors and stimulated by β2-adrenergic receptors. The net effect of norepinephrine from sympathetic nerves and epinephrine from adrenal glands on insulin release is inhibition due to dominance of the α-adrenergic receptors.
When the glucose level comes down to the usual physiologic value, insulin release from the β-cells slows or stops. If the blood glucose level drops lower than this, especially to dangerously low levels, release of hyperglycemic hormones (most prominently glucagon from islet of Langerhans alpha cells) forces release of glucose into the blood from the liver glycogen stores, supplemented by gluconeogenesis if the glycogen stores become depleted. By increasing blood glucose, the hyperglycemic hormones prevent or correct life-threatening hypoglycemia.
Evidence of impaired first-phase insulin release can be seen in the glucose tolerance test, demonstrated by a substantially elevated blood glucose level at 30 minutes after the ingestion of a glucose load (75 or 100 g of glucose), followed by a slow drop over the next 100 minutes, to remain above 120 mg/100 ml after two hours after the start of the test. In a normal person the blood glucose level is corrected (and may even be slightly over-corrected) by the end of the test.
## Oscillations
Even during digestion, in general, one or two hours following a meal, insulin release from the pancreas is not continuous, but oscillates with a period of 3–6 minutes, changing from generating a blood insulin concentration more than about 800 p mol/l to less than 100 pmol/l. This is thought to avoid downregulation of insulin receptors in target cells, and to assist the liver in extracting insulin from the blood. This oscillation is important to consider when administering insulin-stimulating medication, since it is the oscillating blood concentration of insulin release, which should, ideally, be achieved, not a constant high concentration. This may be achieved by delivering insulin rhythmically to the portal vein or by islet cell transplantation to the liver.
## Blood insulin level
The blood insulin level can be measured in international units, such as µIU/mL or in molar concentration, such as pmol/L, where 1 µIU/mL equals 6.945 pmol/L. A typical blood level between meals is 8–11 μIU/mL (57–79 pmol/L).
## Signal transduction
The effects of insulin are initiated by its binding to a receptor present in the cell membrane. The receptor molecule contains an α- and β subunits. Two molecules are joined to form what is known as a homodimer. Insulin binds to the α-subunits of the homodimer, which faces the extracellular side of the cells. The β subunits have tyrosine kinase enzyme activity which is triggered by the insulin binding. This activity provokes the autophosphorylation of the β subunits and subsequently the phosphorylation of proteins inside the cell known as insulin receptor substrates (IRS). The phosphorylation of the IRS activates a signal transduction cascade that leads to the activation of other kinases as well as transcription factors that mediate the intracellular effects of insulin.
The cascade that leads to the insertion of GLUT4 glucose transporters into the cell membranes of muscle and fat cells, and to the synthesis of glycogen in liver and muscle tissue, as well as the conversion of glucose into triglycerides in liver, adipose, and lactating mammary gland tissue, operates via the activation, by IRS-1, of phosphoinositol 3 kinase (PI3K). This enzyme converts a phospholipid in the cell membrane by the name of phosphatidylinositol 4,5-bisphosphate (PIP2), into phosphatidylinositol 3,4,5-triphosphate (PIP3), which, in turn, activates protein kinase B (PKB). Activated PKB facilitates the fusion of GLUT4 containing endosomes with the cell membrane, resulting in an increase in GLUT4 transporters in the plasma membrane. PKB also phosphorylates glycogen synthase kinase (GSK), thereby inactivating this enzyme. This means that its substrate, glycogen synthase (GS), cannot be phosphorylated, and remains dephosphorylated, and therefore active. The active enzyme, glycogen synthase (GS), catalyzes the rate limiting step in the synthesis of glycogen from glucose. Similar dephosphorylations affect the enzymes controlling the rate of glycolysis leading to the synthesis of fats via malonyl-CoA in the tissues that can generate triglycerides, and also the enzymes that control the rate of gluconeogenesis in the liver. The overall effect of these final enzyme dephosphorylations is that, in the tissues that can carry out these reactions, glycogen and fat synthesis from glucose are stimulated, and glucose production by the liver through glycogenolysis and gluconeogenesis are inhibited. The breakdown of triglycerides by adipose tissue into free fatty acids and glycerol is also inhibited.
After the intracellular signal that resulted from the binding of insulin to its receptor has been produced, termination of signaling is then needed. As mentioned below in the section on degradation, endocytosis and degradation of the receptor bound to insulin is a main mechanism to end signaling. In addition, the signaling pathway is also terminated by dephosphorylation of the tyrosine residues in the various signaling pathways by tyrosine phosphatases. Serine/Threonine kinases are also known to reduce the activity of insulin.
The structure of the insulin–insulin receptor complex has been determined using the techniques of X-ray crystallography.
## Physiological effects
The actions of insulin on the global human metabolism level include:
- Increase of cellular intake of certain substances, most prominently glucose in muscle and adipose tissue (about two-thirds of body cells)
- Increase of DNA replication and protein synthesis via control of amino acid uptake
- Modification of the activity of numerous enzymes.
The actions of insulin (indirect and direct) on cells include:
- Stimulates the uptake of glucose – Insulin decreases blood glucose concentration by inducing intake of glucose by the cells. This is possible because Insulin causes the insertion of the GLUT4 transporter in the cell membranes of muscle and fat tissues which allows glucose to enter the cell.
- Increased fat synthesis – insulin forces fat cells to take in blood glucose, which is converted into triglycerides; decrease of insulin causes the reverse.
- Increased esterification of fatty acids – forces adipose tissue to make neutral fats (i.e., triglycerides) from fatty acids; decrease of insulin causes the reverse.
- Decreased lipolysis – forces reduction in conversion of fat cell lipid stores into blood fatty acids and glycerol; decrease of insulin causes the reverse.
- Induce glycogen synthesis – When glucose levels are high, insulin induces the formation of glycogen by the activation of the hexokinase enzyme, which adds a phosphate group in glucose, thus resulting in a molecule that cannot exit the cell. At the same time, insulin inhibits the enzyme glucose-6-phosphatase, which removes the phosphate group. These two enzymes are key for the formation of glycogen. Also, insulin activates the enzymes phosphofructokinase and glycogen synthase which are responsible for glycogen synthesis.
- Decreased gluconeogenesis and glycogenolysis – decreases production of glucose from noncarbohydrate substrates, primarily in the liver (the vast majority of endogenous insulin arriving at the liver never leaves the liver); increase of insulin causes glucose production by the liver from assorted substrates.
- Decreased proteolysis – decreasing the breakdown of protein
- Decreased autophagy – decreased level of degradation of damaged organelles. Postprandial levels inhibit autophagy completely.
- Increased amino acid uptake – forces cells to absorb circulating amino acids; decrease of insulin inhibits absorption.
- Arterial muscle tone – forces arterial wall muscle to relax, increasing blood flow, especially in microarteries; decrease of insulin reduces flow by allowing these muscles to contract.
- Increase in the secretion of hydrochloric acid by parietal cells in the stomach.
- Increased potassium uptake – forces cells synthesizing glycogen (a very spongy, "wet" substance, that increases the content of intracellular water, and its accompanying K+ ions) to absorb potassium from the extracellular fluids; lack of insulin inhibits absorption. Insulin's increase in cellular potassium uptake lowers potassium levels in blood plasma. This possibly occurs via insulin-induced translocation of the Na+/K+-ATPase to the surface of skeletal muscle cells.
- Decreased renal sodium excretion.
Insulin also influences other body functions, such as vascular compliance and cognition. Once insulin enters the human brain, it enhances learning and memory and benefits verbal memory in particular. Enhancing brain insulin signaling by means of intranasal insulin administration also enhances the acute thermoregulatory and glucoregulatory response to food intake, suggesting that central nervous insulin contributes to the co-ordination of a wide variety of homeostatic or regulatory processes in the human body. Insulin also has stimulatory effects on gonadotropin-releasing hormone from the hypothalamus, thus favoring fertility.
## Degradation
Once an insulin molecule has docked onto the receptor and effected its action, it may be released back into the extracellular environment, or it may be degraded by the cell. The two primary sites for insulin clearance are the liver and the kidney. The liver clears most insulin during first-pass transit, whereas the kidney clears most of the insulin in systemic circulation. Degradation normally involves endocytosis of the insulin-receptor complex, followed by the action of insulin-degrading enzyme. An insulin molecule produced endogenously by the beta cells is estimated to be degraded within about one hour after its initial release into circulation (insulin half-life ~ 4–6 minutes).
## Regulator of endocannabinoid metabolism
Insulin is a major regulator of endocannabinoid (EC) metabolism and insulin treatment has been shown to reduce intracellular ECs, the 2-arachidonylglycerol (2-AG) and anandamide (AEA), which correspond with insulin-sensitive expression changes in enzymes of EC metabolism. In insulin-resistant adipocytes, patterns of insulin-induced enzyme expression is disturbed in a manner consistent with elevated EC synthesis and reduced EC degradation. Findings suggest that insulin-resistant adipocytes fail to regulate EC metabolism and decrease intracellular EC levels in response to insulin stimulation, whereby obese insulin-resistant individuals exhibit increased concentrations of ECs. This dysregulation contributes to excessive visceral fat accumulation and reduced adiponectin release from abdominal adipose tissue, and further to the onset of several cardiometabolic risk factors that are associated with obesity and type 2 diabetes.
# Hypoglycemia
Hypoglycemia, also known as "low blood sugar", is when blood sugar decreases to below normal levels. This may result in a variety of symptoms including clumsiness, trouble talking, confusion, loss of consciousness, seizures or death. A feeling of hunger, sweating, shakiness and weakness may also be present. Symptoms typically come on quickly.
The most common cause of hypoglycemia is medications used to treat diabetes mellitus such as insulin and sulfonylureas. Risk is greater in diabetics who have eaten less than usual, exercised more than usual or have drunk alcohol. Other causes of hypoglycemia include kidney failure, certain tumors, such as insulinoma, liver disease, hypothyroidism, starvation, inborn error of metabolism, severe infections, reactive hypoglycemia and a number of drugs including alcohol. Low blood sugar may occur in otherwise healthy babies who have not eaten for a few hours.
# Diseases and syndromes
There are several conditions in which insulin disturbance is pathologic:
- Diabetes mellitus – general term referring to all states characterized by hyperglycemia
Type 1 – autoimmune-mediated destruction of insulin-producing β-cells in the pancreas, resulting in absolute insulin deficiency
Type 2 – either inadequate insulin production by the β-cells or insulin resistance or both because of reasons not completely understood.
there is correlation with diet, with sedentary lifestyle, with obesity, with age and with metabolic syndrome. Causality has been demonstrated in multiple model organisms including mice and monkeys; Importantly, non-obese people do get Type 2 diabetes due to diet, sedentary lifestyle and unknown risk factors.
it is likely that there is genetic susceptibility to develop Type 2 diabetes under certain environmental conditions
Other types of impaired glucose tolerance (see the Diabetes)
- Type 1 – autoimmune-mediated destruction of insulin-producing β-cells in the pancreas, resulting in absolute insulin deficiency
- Type 2 – either inadequate insulin production by the β-cells or insulin resistance or both because of reasons not completely understood.
there is correlation with diet, with sedentary lifestyle, with obesity, with age and with metabolic syndrome. Causality has been demonstrated in multiple model organisms including mice and monkeys; Importantly, non-obese people do get Type 2 diabetes due to diet, sedentary lifestyle and unknown risk factors.
it is likely that there is genetic susceptibility to develop Type 2 diabetes under certain environmental conditions
- there is correlation with diet, with sedentary lifestyle, with obesity, with age and with metabolic syndrome. Causality has been demonstrated in multiple model organisms including mice and monkeys; Importantly, non-obese people do get Type 2 diabetes due to diet, sedentary lifestyle and unknown risk factors.
- it is likely that there is genetic susceptibility to develop Type 2 diabetes under certain environmental conditions
- Other types of impaired glucose tolerance (see the Diabetes)
- Insulinoma – a tumor of beta cells producing excess insulin or reactive hypoglycemia.
- Metabolic syndrome – a poorly understood condition first called Syndrome X by Gerald Reaven. It is currently not clear whether the syndrome has a single, treatable cause, or is the result of body changes leading to type 2 diabetes. It is characterized by elevated blood pressure, dyslipidemia (disturbances in blood cholesterol forms and other blood lipids), and increased waist circumference (at least in populations in much of the developed world). The basic underlying cause may be the insulin resistance that precedes type 2 diabetes, which is a diminished capacity for insulin response in some tissues (e.g., muscle, fat). It is common for morbidities such as essential hypertension, obesity, type 2 diabetes, and cardiovascular disease (CVD) to develop.
- Polycystic ovary syndrome – a complex syndrome in women in the reproductive years where anovulation and androgen excess are commonly displayed as hirsutism. In many cases of PCOS, insulin resistance is present.
# Medical uses
Biosynthetic human insulin (insulin human rDNA, INN) for clinical use is manufactured by recombinant DNA technology. Biosynthetic human insulin has increased purity when compared with extractive animal insulin, enhanced purity reducing antibody formation. Researchers have succeeded in introducing the gene for human insulin into plants as another method of producing insulin ("biopharming") in safflower. This technique is anticipated to reduce production costs.
Several analogs of human insulin are available. These insulin analogs are closely related to the human insulin structure, and were developed for specific aspects of glycemic control in terms of fast action (prandial insulins) and long action (basal insulins). The first biosynthetic insulin analog was developed for clinical use at mealtime (prandial insulin), Humalog (insulin lispro), it is more rapidly absorbed after subcutaneous injection than regular insulin, with an effect 15 minutes after injection. Other rapid-acting analogues are NovoRapid and Apidra, with similar profiles. All are rapidly absorbed due to amino acid sequences that will reduce formation of dimers and hexamers (monomeric insulins are more rapidly absorbed). Fast acting insulins do not require the injection-to-meal interval previously recommended for human insulin and animal insulins. The other type is long acting insulin; the first of these was Lantus (insulin glargine). These have a steady effect for an extended period from 18 to 24 hours. Likewise, another protracted insulin analogue (Levemir) is based on a fatty acid acylation approach. A myristic acid molecule is attached to this analogue, which associates the insulin molecule to the abundant serum albumin, which in turn extends the effect and reduces the risk of hypoglycemia. Both protracted analogues need to be taken only once daily, and are used for type 1 diabetics as the basal insulin. A combination of a rapid acting and a protracted insulin is also available, making it more likely for patients to achieve an insulin profile that mimics that of the body´s own insulin release.
Insulin is usually taken as subcutaneous injections by single-use syringes with needles, via an insulin pump, or by repeated-use insulin pens with disposable needles. Inhaled insulin is also available in the U.S. market now.
Synthetic insulin can trigger adverse effects, so some people with diabetes rely on animal-source insulin.
Unlike many medicines, insulin currently cannot be taken orally because, like nearly all other proteins introduced into the gastrointestinal tract, it is reduced to fragments, whereupon all activity is lost. There has been some research into ways to protect insulin from the digestive tract, so that it can be administered orally or sublingually.
# History of study
## Discovery
In 1869, while studying the structure of the pancreas under a microscope, Paul Langerhans, a medical student in Berlin, identified some previously unnoticed tissue clumps scattered throughout the bulk of the pancreas. The function of the "little heaps of cells", later known as the islets of Langerhans, initially remained unknown, but Édouard Laguesse later suggested they might produce secretions that play a regulatory role in digestion. Paul Langerhans' son, Archibald, also helped to understand this regulatory role. The term "insulin" originates from insula, the Latin word for islet/island.
In 1889, the physician Oskar Minkowski, in collaboration with Joseph von Mering, removed the pancreas from a healthy dog to test its assumed role in digestion. On testing the urine, they found sugar, establishing for the first time a relationship between the pancreas and diabetes. In 1901, another major step was taken by the American physician and scientist Eugene Lindsay Opie, when he isolated the role of the pancreas to the islets of Langerhans: "Diabetes mellitus when the result of a lesion of the pancreas is caused by destruction of the islands of Langerhans and occurs only when these bodies are in part or wholly destroyed".
Over the next two decades researchers made several attempts to isolate the islets' secretions. In 1906 George Ludwig Zuelzer achieved partial success in treating dogs with pancreatic extract, but he was unable to continue his work. Between 1911 and 1912, E.L. Scott at the University of Chicago tried aqueous pancreatic extracts and noted "a slight diminution of glycosuria", but was unable to convince his director of his work's value; it was shut down. Israel Kleiner demonstrated similar effects at Rockefeller University in 1915, but World War I interrupted his work and he did not return to it.
In 1916, Nicolae Paulescu developed an aqueous pancreatic extract which, when injected into a diabetic dog, had a normalizing effect on blood-sugar levels. He had to interrupt his experiments because of World War I, and in 1921 he wrote four papers about his work carried out in Bucharest and his tests on a diabetic dog. Later that year, he published "Research on the Role of the Pancreas in Food Assimilation".
## Extraction and purification
In October 1920, Canadian Frederick Banting concluded that the digestive secretions that Minkowski had originally studied were breaking down the islet secretion, thereby making it impossible to extract successfully. A surgeon by training, Banting knew certain arteries could be tied off that would lead most of the pancreas to atrophy, while leaving the islets of Langerhans intact. He reasoned that a relatively pure extract could be made from the islets once most of the rest of the pancreas was gone. He jotted a note to himself: "Ligate pancreatic ducts of the dog. Keep dogs alive till acini degenerate leaving islets. Try to isolate internal secretion of these and relieve glycosuria."
In the spring of 1921, Banting traveled to Toronto to explain his idea to J.J.R. Macleod, Professor of Physiology at the University of Toronto. Macleod was initially skeptical, since Banting had no background in research and was not familiar with the latest literature, but he agreed to provide lab space for Banting to test out his ideas. Macleod also arranged for two undergraduates to be Banting's lab assistants that summer, but Banting required only one lab assistant. Charles Best and Clark Noble flipped a coin; Best won the coin toss and took the first shift. This proved unfortunate for Noble, as Banting kept Best for the entire summer and eventually shared half his Nobel Prize money and credit for the discovery with Best. On 30 July 1921, Banting and Best successfully isolated an extract ("isleton") from the islets of a duct-tied dog and injected it into a diabetic dog, finding that the extract reduced its blood sugar by 40% in 1 hour.
Banting and Best presented their results to Macleod on his return to Toronto in the fall of 1921, but Macleod pointed out flaws with the experimental design, and suggested the experiments be repeated with more dogs and better equipment. He moved Banting and Best into a better laboratory and began paying Banting a salary from his research grants. Several weeks later, the second round of experiments was also a success, and Macleod helped publish their results privately in Toronto that November. Bottlenecked by the time-consuming task of duct-tying dogs and waiting several weeks to extract insulin, Banting hit upon the idea of extracting insulin from the fetal calf pancreas, which had not yet developed digestive glands. By December, they had also succeeded in extracting insulin from the adult cow pancreas. Macleod discontinued all other research in his laboratory to concentrate on the purification of insulin. He invited biochemist James Collip to help with this task, and the team felt ready for a clinical test within a month.
On January 11, 1922, Leonard Thompson, a 14-year-old diabetic who lay dying at the Toronto General Hospital, was given the first injection of insulin. However, the extract was so impure that Thompson suffered a severe allergic reaction, and further injections were cancelled. Over the next 12 days, Collip worked day and night to improve the ox-pancreas extract. A second dose was injected on January 23, completely eliminating the glycosuria that was typical of diabetes without causing any obvious side-effects. The first American patient was Elizabeth Hughes, the daughter of U.S. Secretary of State Charles Evans Hughes. The first patient treated in the U.S. was future woodcut artist James D. Havens; Dr. John Ralston Williams imported insulin from Toronto to Rochester, New York, to treat Havens.
Banting and Best never worked well with Collip, regarding him as something of an interloper, and Collip left the project soon after. Over the spring of 1922, Best managed to improve his techniques to the point where large quantities of insulin could be extracted on demand, but the preparation remained impure. The drug firm Eli Lilly and Company had offered assistance not long after the first publications in 1921, and they took Lilly up on the offer in April. In November, Lilly's head chemist, George B. Walden discovered isoelectric precipitation and was able to produce large quantities of highly refined insulin. Shortly thereafter, insulin was offered for sale to the general public.
## Synthesis
Purified animal-sourced insulin was initially the only type of insulin available to diabetics. The amino acid structure of insulin was characterized in the early 1950s by Frederick Sanger, and the first synthetic insulin was produced simultaneously in the labs of Panayotis Katsoyannis at the University of Pittsburgh and Helmut Zahn at RWTH Aachen University in the early 1960s. Synthetic crystalline bovine insulin was achieved by Chinese researchers in 1965.
The first genetically engineered, synthetic "human" insulin was produced using E. coli in 1978 by Arthur Riggs and Keiichi Itakura at the Beckman Research Institute of the City of Hope in collaboration with Herbert Boyer at Genentech. Genentech, founded by Swanson, Boyer and Eli Lilly and Company, went on in 1982 to sell the first commercially available biosynthetic human insulin under the brand name Humulin. The vast majority of insulin currently used worldwide is now biosynthetic recombinant "human" insulin or its analogues.
Recombinant insulin is produced either in yeast (usually Saccharomyces cerevisiae) or E. coli. In yeast, insulin may be engineered as a single-chain protein with a KexII endoprotease (a yeast homolog of PCI/PCII) site that separates the insulin A chain from a c-terminally truncated insulin B chain. A chemically synthesized c-terminal tail is then grafted onto insulin by reverse proteolysis using the inexpensive protease trypsin; typically the lysine on the c-terminal tail is protected with a chemical protecting group to prevent proteolysis. The ease of modular synthesis and the relative safety of modifications in that region accounts for common insulin analogs with c-terminal modifications (e.g. lispro, aspart, glulisine). The Genentech synthesis and completely chemical synthesis such as that by Bruce Merrifield are not preferred because the efficiency of recombining the two insulin chains is low, primarily due to competition with the precipitation of insulin B chain.
## Nobel Prizes
The Nobel Prize committee in 1923 credited the practical extraction of insulin to a team at the University of Toronto and awarded the Nobel Prize to two men: Frederick Banting and J.J.R. Macleod. They were awarded the Nobel Prize in Physiology or Medicine in 1923 for the discovery of insulin. Banting, insisted that Best was not mentioned, shared his prize with him, and Macleod immediately shared his with James Collip. The patent for insulin was sold to the University of Toronto for one dollar.
Two other Nobel Prizes have been awarded for work on insulin. British molecular biologist Frederick Sanger determined the primary structure of insulin in 1955, making it the first protein to be sequenced. Sanger was awarded the 1958 Nobel Prize in Chemistry for this work. Rosalyn Sussman Yalow received the 1977 Nobel Prize in Medicine for the development of the radioimmunoassay for insulin.
Several Nobel Prizes also have an indirect connection with insulin. George Minot, co-recipient of the 1934 Nobel Prize for the development of the first effective treatment for pernicious anemia, had diabetes mellitus. Dr. William Castle observed that the 1921 discovery of insulin, arriving in time to keep Minot alive, was therefore also responsible for the discovery of a cure for pernicious anemia. Dorothy Hodgkin was awarded a Nobel Prize in Chemistry in 1964 for the development of crystallography. In 1969, after decades of work, Hodgkin determined the spatial conformation of insulin, the so-called tertiary structure, by means of X-ray diffraction studies.
### Controversy
The work published by Banting, Best, Collip and Macleod represented the preparation of purified insulin extract suitable for use on human patients. Although Paulescu discovered the principles of the treatment, his saline extract could not be used on humans; he was not mentioned in the 1923 Nobel Prize. Professor Ian Murray was particularly active in working to correct "the historical wrong" against Nicolae Paulescu. Murray was a professor of physiology at the Anderson College of Medicine in Glasgow, Scotland, the head of the department of Metabolic Diseases at a leading Glasgow hospital, vice-president of the British Association of Diabetes, and a founding member of the International Diabetes Federation. Murray wrote:
Insufficient recognition has been given to Paulescu, the distinguished Romanian scientist, who at the time when the Toronto team were commencing their research had already succeeded in extracting the antidiabetic hormone of the pancreas and proving its efficacy in reducing the hyperglycaemia in diabetic dogs.
In a private communication, Professor Arne Tiselius, former head of the Nobel Institute, expressed his personal opinion that Paulescu was equally worthy of the award in 1923. | Insulin
Insulin (from Latin insula, island) is a peptide hormone produced by beta cells of the pancreatic islets; it is considered to be the main anabolic hormone of the body.[1] It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of carbohydrates, especially glucose from the blood into liver, fat and skeletal muscle cells.[2] In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both.[2] Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood.[3] Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat.
Beta cells are sensitive to glucose concentrations, also known as blood sugar levels. When the glucose level is high, the beta cells secrete insulin into the blood; when glucose levels are low, secretion of insulin is inhibited.[4] Their neighboring alpha cells, by taking their cues from the beta cells,[4] secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high.[2][4] Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin.[2][4] The secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism of glucose homeostasis.[4]
If beta cells are destroyed by an autoimmune reaction, insulin can no longer be synthesized or be secreted into the blood. This results in type 1 diabetes mellitus, which is characterized by abnormally high blood glucose concentrations, and generalized body wasting.[5] In type 2 diabetes mellitus the destruction of beta cells is less pronounced than in type 1 diabetes, and is not due to an autoimmune process. Instead there is an accumulation of amyloid in the pancreatic islets, which likely disrupts their anatomy and physiology.[4] The pathogenesis of type 2 diabetes is not well understood but patients exhibit a reduced population of islet beta-cells, reduced secretory function of islet beta-cells that survive, and peripheral tissue insulin resistance.[1] Type 2 diabetes is characterized by high rates of glucagon secretion into the blood which are unaffected by, and unresponsive to the concentration of glucose in the blood. Insulin is still secreted into the blood in response to the blood glucose.[4] As a result, the insulin levels, even when the blood sugar level is normal, are much higher than they are in healthy persons.
The human insulin protein is composed of 51 amino acids, and has a molecular mass of 5808 Da. It is a dimer of an A-chain and a B-chain, which are linked together by disulfide bonds. Insulin's structure varies slightly between species of animals. Insulin from animal sources differs somewhat in effectiveness (in carbohydrate metabolism effects) from human insulin because of these variations. Porcine insulin is especially close to the human version, and was widely used to treat type 1 diabetics before human insulin could be produced in large quantities by recombinant DNA technologies.[6][7][8][9]
The crystal structure of insulin in the solid state was determined by Dorothy Hodgkin. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.[10]
# Evolution and species distribution
Insulin may have originated more than a billion years ago.[11] The molecular origins of insulin go at least as far back as the simplest unicellular eukaryotes.[12] Apart from animals, insulin-like proteins are also known to exist in the Fungi and Protista kingdoms.[11]
Insulin is produced by beta cells of the pancreatic islets in most vertebrates and by the Brockmann body in some teleost fish.[13] Cone snails Conus geographus and Conus tulipa, venomous sea snails that hunt small fish, use modified forms of insulin in their venom cocktails. The insulin toxin, closer in structure to fishes' than to snails' native insulin, slows down the prey fishes by lowering their blood glucose levels.[14][15]
# Gene
The preproinsulin precursor of insulin is encoded by the INS gene.[16][17]
## Alleles
A variety of mutant alleles with changes in the coding region have been identified. A read-through gene, INS-IGF2, overlaps with this gene at the 5' region and with the IGF2 gene at the 3' region.[16]
## Regulation
In the pancreatic β cells, glucose is the primary physiological stimulus for the regulation of insulin synthesis. Insulin is mainly regulated through the transcription factors PDX1, NeuroD1, and MafA.[18][19][20][21]
PDX1 (Pancreatic and duodenal homeobox protein 1) is in the nuclear periphery upon low blood glucose levels[22] interacting with corepressors HDAC1 and 2 which is downregulating the insulin secretion.[23] An increase in blood glucose levels causes phosphorylation of PDX1 and it translocates centrally and binds the A3 element within the insulin promoter.[24] Upon translocation it interacts with coactivators HAT p300 and acetyltransferase set 7/9. PDX1 affects the histone modifications through acetylation and deacetylation as well as methylation. It is also said to suppress glucagon.[25]
NeuroD1, also known as β2, regulates insulin exocytosis in pancreatic β cells by directly inducing the expression of genes involved in exocytosis.[26] It is localized in the cytosol, but in response to high glucose it becomes glycosylated by OGT and/or phosphorylated by ERK, which causes translocation to the nucleus. In the nucleus β2 heterodimerizes with E47, binds to the E1 element of the insulin promoter and recruits co-activator p300 which acetylates β2. It is able to interact with other transcription factors as well in activation of the insulin gene.[26]
MafA is degraded by proteasomes upon low blood glucose levels. Increased levels of glucose make an unknown protein glycosylated. This protein works as a transcription factor for MafA in an unknown manner and MafA is transported out of the cell. MafA is then translocated back into the nucleus where it binds the C1 element of the insulin promoter.[27][28]
These transcription factors work synergistically and in a complex arrangement. Increased blood glucose can after a while destroy the binding capacities of these proteins, and therefore reduce the amount of insulin secreted, causing diabetes. The decreased binding activities can be mediated by glucose induced oxidative stress and antioxidants are said to prevent the decreased insulin secretion in glucotoxic pancreatic β cells. Stress signalling molecules and reactive oxygen species inhibits the insulin gene by interfering with the cofactors binding the transcription factors and the transcription factors it self.[29]
Several regulatory sequences in the promoter region of the human insulin gene bind to transcription factors. In general, the A-boxes bind to Pdx1 factors, E-boxes bind to NeuroD, C-boxes bind to MafA, and cAMP response elements to CREB. There are also silencers that inhibit transcription.
# Protein structure
Within vertebrates, the amino acid sequence of insulin is strongly conserved. Bovine insulin differs from human in only three amino acid residues, and porcine insulin in one. Even insulin from some species of fish is similar enough to human to be clinically effective in humans. Insulin in some invertebrates is quite similar in sequence to human insulin, and has similar physiological effects. The strong homology seen in the insulin sequence of diverse species suggests that it has been conserved across much of animal evolutionary history. The C-peptide of proinsulin (discussed later), however, differs much more among species; it is also a hormone, but a secondary one.
The primary structure of bovine insulin was first determined by Frederick Sanger in 1951.[32] After that, this polypeptide was synthesized independently by several groups.[33][34][35] The 3-dimensional structure of insulin was determined by X-ray crystallography in Dorothy Hodgkin's laboratory in 1969 (PDB file 1ins).[36]
Insulin is produced and stored in the body as a hexamer (a unit of six insulin molecules), while the active form is the monomer. The hexamer is an inactive form with long-term stability, which serves as a way to keep the highly reactive insulin protected, yet readily available. The hexamer-monomer conversion is one of the central aspects of insulin formulations for injection. The hexamer is far more stable than the monomer, which is desirable for practical reasons; however, the monomer is a much faster-reacting drug because diffusion rate is inversely related to particle size. A fast-reacting drug means insulin injections do not have to precede mealtimes by hours, which in turn gives people with diabetes more flexibility in their daily schedules.[37] Insulin can aggregate and form fibrillar interdigitated beta-sheets. This can cause injection amyloidosis, and prevents the storage of insulin for long periods.[38]
# Synthesis, physiological effects, and degradation
## Synthesis
Insulin is produced in the pancreas and the Brockmann body (in some fish), and released when any of several stimuli are detected. These stimuli include ingested protein and glucose in the blood produced from digested food.[39] Carbohydrates can be polymers of simple sugars or the simple sugars themselves. If the carbohydrates include glucose, then that glucose will be absorbed into the bloodstream and blood glucose level will begin to rise. In target cells, insulin initiates a signal transduction, which has the effect of increasing glucose uptake and storage. Finally, insulin is degraded, terminating the response.
In mammals, insulin is synthesized in the pancreas within the beta cells. One million to three million pancreatic islets form the endocrine part of the pancreas, which is primarily an exocrine gland. The endocrine portion accounts for only 2% of the total mass of the pancreas. Within the pancreatic islets, beta cells constitute 65–80% of all the cells.
Insulin consists of two polypeptide chains, the A- and B- chains, linked together by disulfide bonds. It is however first synthesized as a single polypeptide called preproinsulin in beta cells. Preproinsulin contains a 24-residue signal peptide which directs the nascent polypeptide chain to the rough endoplasmic reticulum (RER). The signal peptide is cleaved as the polypeptide is translocated into lumen of the RER, forming proinsulin.[40] In the RER the proinsulin folds into the correct conformation and 3 disulfide bonds are formed. About 5–10 min after its assembly in the endoplasmic reticulum, proinsulin is transported to the trans-Golgi network (TGN) where immature granules are formed. Transport to the TGN may take about 30 min.
Proinsulin undergoes maturation into active insulin through the action of cellular endopeptidases known as prohormone convertases (PC1 and PC2), as well as the exoprotease carboxypeptidase E.[41] The endopeptidases cleave at 2 positions, releasing a fragment called the C-peptide, and leaving 2 peptide chains, the B- and A- chains, linked by 2 disulfide bonds. The cleavage sites are each located after a pair of basic residues (lysine-64 and arginine-65, and arginine-31 and −32). After cleavage of the C-peptide, these 2 pairs of basic residues are removed by the carboxypeptidase.[42] The C-peptide is the central portion of proinsulin, and the primary sequence of proinsulin goes in the order "B-C-A" (the B and A chains were identified on the basis of mass and the C-peptide was discovered later).
The resulting mature insulin is packaged inside mature granules waiting for metabolic signals (such as leucine, arginine, glucose and mannose) and vagal nerve stimulation to be exocytosed from the cell into the circulation.[43]
The endogenous production of insulin is regulated in several steps along the synthesis pathway:
- At transcription from the insulin gene
- In mRNA stability
- At the mRNA translation
- In the posttranslational modifications
Insulin and its related proteins have been shown to be produced inside the brain, and reduced levels of these proteins are linked to Alzheimer's disease.[44][45][46]
Insulin release is stimulated also by beta-2 receptor stimulation and inhibited by alpha-1 receptor stimulation. In addition, cortisol, glucagon and growth hormone antagonize the actions of insulin during times of stress. Insulin also inhibits fatty acid release by hormone sensitive lipase in adipose tissue.[2]
## Release
Beta cells in the islets of Langerhans release insulin in two phases. The first-phase release is rapidly triggered in response to increased blood glucose levels, and lasts about 10 minutes. The second phase is a sustained, slow release of newly formed vesicles triggered independently of sugar, peaking in 2 to 3 hours. Reduced first-phase insulin release may be the earliest detectable beta cell defect predicting onset of type 2 diabetes.[47] First-phase release and insulin sensitivity are independent predictors of diabetes.[48]
The description of first phase release is as follows:
- Glucose enters the β-cells through the glucose transporters, GLUT2. These glucose transporters have a relatively low affinity for glucose, ensuring that the rate of glucose entry into the β-cells is proportional to the extracellular glucose concentration (within the physiological range). At low blood sugar levels very little glucose enters the β-cells; at high blood glucose concentrations large quantities of glucose enter these cells.[49]
- The glucose that enters the β-cell is phosphorylated to glucose-6-phosphate (G-6-P) by glucokinase (hexokinase IV) which is not inhibited by G-6-P in the way that the hexokinases in other tissues (hexokinase I – III) are affected by this product. This means that the intracellular G-6-P concentration remains proportional to the blood sugar concentration.[4][49]
- Glucose-6-phosphate enters glycolytic pathway and then, via the pyruvate dehydrogenase reaction, into the Krebs cycle, where multiple, high-energy ATP molecules are produced by the oxidation of acetyl CoA (the Krebs cycle substrate), leading to a rise in the ATP:ADP ratio within the cell.[50]
- An increased intracellular ATP:ADP ratio closes the ATP-sensitive SUR1/Kir6.2 potassium channel (see sulfonylurea receptor). This prevents potassium ions (K+) from leaving the cell by facilitated diffusion, leading to a buildup of intracellular potassium ions. As a result, the inside of the cell becomes less negative with respect to the outside, leading to the depolarization of the cell surface membrane.
- Upon depolarization, voltage-gated calcium ion (Ca2+) channels open, allowing calcium ions to move into the cell by facilitated diffusion.
- The cytosolic calcium ion concentration can also be increased by calcium release from intracellular stores via activation of ryanodine receptors.[51]
- The calcium ion concentration in the cytosol of the beta cells can also, or additionally, be increased through the activation of phospholipase C resulting from the binding of an extracellular ligand (hormone or neurotransmitter) to a G protein-coupled membrane receptor. Phospholipase C cleaves the membrane phospholipid, phosphatidyl inositol 4,5-bisphosphate, into inositol 1,4,5-trisphosphate and diacylglycerol. Inositol 1,4,5-trisphosphate (IP3) then binds to receptor proteins in the plasma membrane of the endoplasmic reticulum (ER). This allows the release of Ca2+ ions from the ER via IP3-gated channels, which raises the cytosolic concentration of calcium ions independently of the effects of a high blood glucose concentration. Parasympathetic stimulation of the pancreatic islets operates via this pathway to increase insulin secretion into the blood.[52]
- The significantly increased amount of calcium ions in the cells' cytoplasm causes the release into the blood of previously synthesized insulin, which has been stored in intracellular secretory vesicles.
This is the primary mechanism for release of insulin. Other substances known to stimulate insulin release include the amino acids arginine and leucine, parasympathetic release of acetylcholine (acting via the phospholipase C pathway), sulfonylurea, cholecystokinin (CCK, also via phospholipase C),[53] and the gastrointestinally derived incretins, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP).
Release of insulin is strongly inhibited by norepinephrine (noradrenaline), which leads to increased blood glucose levels during stress. It appears that release of catecholamines by the sympathetic nervous system has conflicting influences on insulin release by beta cells, because insulin release is inhibited by α2-adrenergic receptors[54] and stimulated by β2-adrenergic receptors.[55] The net effect of norepinephrine from sympathetic nerves and epinephrine from adrenal glands on insulin release is inhibition due to dominance of the α-adrenergic receptors.[56]
When the glucose level comes down to the usual physiologic value, insulin release from the β-cells slows or stops. If the blood glucose level drops lower than this, especially to dangerously low levels, release of hyperglycemic hormones (most prominently glucagon from islet of Langerhans alpha cells) forces release of glucose into the blood from the liver glycogen stores, supplemented by gluconeogenesis if the glycogen stores become depleted. By increasing blood glucose, the hyperglycemic hormones prevent or correct life-threatening hypoglycemia.
Evidence of impaired first-phase insulin release can be seen in the glucose tolerance test, demonstrated by a substantially elevated blood glucose level at 30 minutes after the ingestion of a glucose load (75 or 100 g of glucose), followed by a slow drop over the next 100 minutes, to remain above 120 mg/100 ml after two hours after the start of the test. In a normal person the blood glucose level is corrected (and may even be slightly over-corrected) by the end of the test.
## Oscillations
Even during digestion, in general, one or two hours following a meal, insulin release from the pancreas is not continuous, but oscillates with a period of 3–6 minutes, changing from generating a blood insulin concentration more than about 800 p mol/l to less than 100 pmol/l.[57] This is thought to avoid downregulation of insulin receptors in target cells, and to assist the liver in extracting insulin from the blood.[57] This oscillation is important to consider when administering insulin-stimulating medication, since it is the oscillating blood concentration of insulin release, which should, ideally, be achieved, not a constant high concentration.[57] This may be achieved by delivering insulin rhythmically to the portal vein or by islet cell transplantation to the liver.[57]
## Blood insulin level
The blood insulin level can be measured in international units, such as µIU/mL or in molar concentration, such as pmol/L, where 1 µIU/mL equals 6.945 pmol/L.[58] A typical blood level between meals is 8–11 μIU/mL (57–79 pmol/L).[59]
## Signal transduction
The effects of insulin are initiated by its binding to a receptor present in the cell membrane. The receptor molecule contains an α- and β subunits. Two molecules are joined to form what is known as a homodimer. Insulin binds to the α-subunits of the homodimer, which faces the extracellular side of the cells. The β subunits have tyrosine kinase enzyme activity which is triggered by the insulin binding. This activity provokes the autophosphorylation of the β subunits and subsequently the phosphorylation of proteins inside the cell known as insulin receptor substrates (IRS). The phosphorylation of the IRS activates a signal transduction cascade that leads to the activation of other kinases as well as transcription factors that mediate the intracellular effects of insulin.[60]
The cascade that leads to the insertion of GLUT4 glucose transporters into the cell membranes of muscle and fat cells, and to the synthesis of glycogen in liver and muscle tissue, as well as the conversion of glucose into triglycerides in liver, adipose, and lactating mammary gland tissue, operates via the activation, by IRS-1, of phosphoinositol 3 kinase (PI3K). This enzyme converts a phospholipid in the cell membrane by the name of phosphatidylinositol 4,5-bisphosphate (PIP2), into phosphatidylinositol 3,4,5-triphosphate (PIP3), which, in turn, activates protein kinase B (PKB). Activated PKB facilitates the fusion of GLUT4 containing endosomes with the cell membrane, resulting in an increase in GLUT4 transporters in the plasma membrane.[61] PKB also phosphorylates glycogen synthase kinase (GSK), thereby inactivating this enzyme.[62] This means that its substrate, glycogen synthase (GS), cannot be phosphorylated, and remains dephosphorylated, and therefore active. The active enzyme, glycogen synthase (GS), catalyzes the rate limiting step in the synthesis of glycogen from glucose. Similar dephosphorylations affect the enzymes controlling the rate of glycolysis leading to the synthesis of fats via malonyl-CoA in the tissues that can generate triglycerides, and also the enzymes that control the rate of gluconeogenesis in the liver. The overall effect of these final enzyme dephosphorylations is that, in the tissues that can carry out these reactions, glycogen and fat synthesis from glucose are stimulated, and glucose production by the liver through glycogenolysis and gluconeogenesis are inhibited.[63] The breakdown of triglycerides by adipose tissue into free fatty acids and glycerol is also inhibited.[63]
After the intracellular signal that resulted from the binding of insulin to its receptor has been produced, termination of signaling is then needed. As mentioned below in the section on degradation, endocytosis and degradation of the receptor bound to insulin is a main mechanism to end signaling.[43] In addition, the signaling pathway is also terminated by dephosphorylation of the tyrosine residues in the various signaling pathways by tyrosine phosphatases. Serine/Threonine kinases are also known to reduce the activity of insulin.
The structure of the insulin–insulin receptor complex has been determined using the techniques of X-ray crystallography.[64]
## Physiological effects
The actions of insulin on the global human metabolism level include:
- Increase of cellular intake of certain substances, most prominently glucose in muscle and adipose tissue (about two-thirds of body cells)[65]
- Increase of DNA replication and protein synthesis via control of amino acid uptake
- Modification of the activity of numerous enzymes.
The actions of insulin (indirect and direct) on cells include:
- Stimulates the uptake of glucose – Insulin decreases blood glucose concentration by inducing intake of glucose by the cells. This is possible because Insulin causes the insertion of the GLUT4 transporter in the cell membranes of muscle and fat tissues which allows glucose to enter the cell.[60]
- Increased fat synthesis – insulin forces fat cells to take in blood glucose, which is converted into triglycerides; decrease of insulin causes the reverse.[65]
- Increased esterification of fatty acids – forces adipose tissue to make neutral fats (i.e., triglycerides) from fatty acids; decrease of insulin causes the reverse.[65]
- Decreased lipolysis – forces reduction in conversion of fat cell lipid stores into blood fatty acids and glycerol; decrease of insulin causes the reverse.[65]
- Induce glycogen synthesis – When glucose levels are high, insulin induces the formation of glycogen by the activation of the hexokinase enzyme, which adds a phosphate group in glucose, thus resulting in a molecule that cannot exit the cell. At the same time, insulin inhibits the enzyme glucose-6-phosphatase, which removes the phosphate group. These two enzymes are key for the formation of glycogen. Also, insulin activates the enzymes phosphofructokinase and glycogen synthase which are responsible for glycogen synthesis.[66]
- Decreased gluconeogenesis and glycogenolysis – decreases production of glucose from noncarbohydrate substrates, primarily in the liver (the vast majority of endogenous insulin arriving at the liver never leaves the liver); increase of insulin causes glucose production by the liver from assorted substrates.[65]
- Decreased proteolysis – decreasing the breakdown of protein[65]
- Decreased autophagy – decreased level of degradation of damaged organelles. Postprandial levels inhibit autophagy completely.[67]
- Increased amino acid uptake – forces cells to absorb circulating amino acids; decrease of insulin inhibits absorption.[65]
- Arterial muscle tone – forces arterial wall muscle to relax, increasing blood flow, especially in microarteries; decrease of insulin reduces flow by allowing these muscles to contract.[68]
- Increase in the secretion of hydrochloric acid by parietal cells in the stomach.[citation needed]
- Increased potassium uptake – forces cells synthesizing glycogen (a very spongy, "wet" substance, that increases the content of intracellular water, and its accompanying K+ ions)[69] to absorb potassium from the extracellular fluids; lack of insulin inhibits absorption. Insulin's increase in cellular potassium uptake lowers potassium levels in blood plasma. This possibly occurs via insulin-induced translocation of the Na+/K+-ATPase to the surface of skeletal muscle cells.[70][71]
- Decreased renal sodium excretion.[72]
Insulin also influences other body functions, such as vascular compliance and cognition. Once insulin enters the human brain, it enhances learning and memory and benefits verbal memory in particular.[73] Enhancing brain insulin signaling by means of intranasal insulin administration also enhances the acute thermoregulatory and glucoregulatory response to food intake, suggesting that central nervous insulin contributes to the co-ordination of a wide variety of homeostatic or regulatory processes in the human body.[74] Insulin also has stimulatory effects on gonadotropin-releasing hormone from the hypothalamus, thus favoring fertility.[75]
## Degradation
Once an insulin molecule has docked onto the receptor and effected its action, it may be released back into the extracellular environment, or it may be degraded by the cell. The two primary sites for insulin clearance are the liver and the kidney. The liver clears most insulin during first-pass transit, whereas the kidney clears most of the insulin in systemic circulation. Degradation normally involves endocytosis of the insulin-receptor complex, followed by the action of insulin-degrading enzyme. An insulin molecule produced endogenously by the beta cells is estimated to be degraded within about one hour after its initial release into circulation (insulin half-life ~ 4–6 minutes).[76][77]
## Regulator of endocannabinoid metabolism
Insulin is a major regulator of endocannabinoid (EC) metabolism and insulin treatment has been shown to reduce intracellular ECs, the 2-arachidonylglycerol (2-AG) and anandamide (AEA), which correspond with insulin-sensitive expression changes in enzymes of EC metabolism. In insulin-resistant adipocytes, patterns of insulin-induced enzyme expression is disturbed in a manner consistent with elevated EC synthesis and reduced EC degradation. Findings suggest that insulin-resistant adipocytes fail to regulate EC metabolism and decrease intracellular EC levels in response to insulin stimulation, whereby obese insulin-resistant individuals exhibit increased concentrations of ECs.[78][79] This dysregulation contributes to excessive visceral fat accumulation and reduced adiponectin release from abdominal adipose tissue, and further to the onset of several cardiometabolic risk factors that are associated with obesity and type 2 diabetes.[80]
# Hypoglycemia
Hypoglycemia, also known as "low blood sugar", is when blood sugar decreases to below normal levels.[81] This may result in a variety of symptoms including clumsiness, trouble talking, confusion, loss of consciousness, seizures or death.[81] A feeling of hunger, sweating, shakiness and weakness may also be present.[81] Symptoms typically come on quickly.[81]
The most common cause of hypoglycemia is medications used to treat diabetes mellitus such as insulin and sulfonylureas.[82][83] Risk is greater in diabetics who have eaten less than usual, exercised more than usual or have drunk alcohol.[81] Other causes of hypoglycemia include kidney failure, certain tumors, such as insulinoma, liver disease, hypothyroidism, starvation, inborn error of metabolism, severe infections, reactive hypoglycemia and a number of drugs including alcohol.[81][83] Low blood sugar may occur in otherwise healthy babies who have not eaten for a few hours.[84]
# Diseases and syndromes
There are several conditions in which insulin disturbance is pathologic:
- Diabetes mellitus – general term referring to all states characterized by hyperglycemia
Type 1 – autoimmune-mediated destruction of insulin-producing β-cells in the pancreas, resulting in absolute insulin deficiency
Type 2 – either inadequate insulin production by the β-cells or insulin resistance or both because of reasons not completely understood.
there is correlation with diet, with sedentary lifestyle, with obesity, with age and with metabolic syndrome. Causality has been demonstrated in multiple model organisms including mice and monkeys; Importantly, non-obese people do get Type 2 diabetes due to diet, sedentary lifestyle and unknown risk factors.
it is likely that there is genetic susceptibility to develop Type 2 diabetes under certain environmental conditions
Other types of impaired glucose tolerance (see the Diabetes)
- Type 1 – autoimmune-mediated destruction of insulin-producing β-cells in the pancreas, resulting in absolute insulin deficiency
- Type 2 – either inadequate insulin production by the β-cells or insulin resistance or both because of reasons not completely understood.
there is correlation with diet, with sedentary lifestyle, with obesity, with age and with metabolic syndrome. Causality has been demonstrated in multiple model organisms including mice and monkeys; Importantly, non-obese people do get Type 2 diabetes due to diet, sedentary lifestyle and unknown risk factors.
it is likely that there is genetic susceptibility to develop Type 2 diabetes under certain environmental conditions
- there is correlation with diet, with sedentary lifestyle, with obesity, with age and with metabolic syndrome. Causality has been demonstrated in multiple model organisms including mice and monkeys; Importantly, non-obese people do get Type 2 diabetes due to diet, sedentary lifestyle and unknown risk factors.
- it is likely that there is genetic susceptibility to develop Type 2 diabetes under certain environmental conditions
- Other types of impaired glucose tolerance (see the Diabetes)
- Insulinoma – a tumor of beta cells producing excess insulin or reactive hypoglycemia.
- Metabolic syndrome – a poorly understood condition first called Syndrome X by Gerald Reaven. It is currently not clear whether the syndrome has a single, treatable cause, or is the result of body changes leading to type 2 diabetes. It is characterized by elevated blood pressure, dyslipidemia (disturbances in blood cholesterol forms and other blood lipids), and increased waist circumference (at least in populations in much of the developed world). The basic underlying cause may be the insulin resistance that precedes type 2 diabetes, which is a diminished capacity for insulin response in some tissues (e.g., muscle, fat). It is common for morbidities such as essential hypertension, obesity, type 2 diabetes, and cardiovascular disease (CVD) to develop.
- Polycystic ovary syndrome – a complex syndrome in women in the reproductive years where anovulation and androgen excess are commonly displayed as hirsutism. In many cases of PCOS, insulin resistance is present.
# Medical uses
Biosynthetic human insulin (insulin human rDNA, INN) for clinical use is manufactured by recombinant DNA technology.[6] Biosynthetic human insulin has increased purity when compared with extractive animal insulin, enhanced purity reducing antibody formation. Researchers have succeeded in introducing the gene for human insulin into plants as another method of producing insulin ("biopharming") in safflower.[85] This technique is anticipated to reduce production costs.
Several analogs of human insulin are available. These insulin analogs are closely related to the human insulin structure, and were developed for specific aspects of glycemic control in terms of fast action (prandial insulins) and long action (basal insulins).[86] The first biosynthetic insulin analog was developed for clinical use at mealtime (prandial insulin), Humalog (insulin lispro),[citation needed] it is more rapidly absorbed after subcutaneous injection than regular insulin, with an effect 15 minutes after injection. Other rapid-acting analogues are NovoRapid and Apidra, with similar profiles. All are rapidly absorbed due to amino acid sequences that will reduce formation of dimers and hexamers (monomeric insulins are more rapidly absorbed). Fast acting insulins do not require the injection-to-meal interval previously recommended for human insulin and animal insulins. The other type is long acting insulin; the first of these was Lantus (insulin glargine). These have a steady effect for an extended period from 18 to 24 hours. Likewise, another protracted insulin analogue (Levemir) is based on a fatty acid acylation approach. A myristic acid molecule is attached to this analogue, which associates the insulin molecule to the abundant serum albumin, which in turn extends the effect and reduces the risk of hypoglycemia. Both protracted analogues need to be taken only once daily, and are used for type 1 diabetics as the basal insulin. A combination of a rapid acting and a protracted insulin is also available, making it more likely for patients to achieve an insulin profile that mimics that of the body´s own insulin release.
Insulin is usually taken as subcutaneous injections by single-use syringes with needles, via an insulin pump, or by repeated-use insulin pens with disposable needles. Inhaled insulin is also available in the U.S. market now.
Synthetic insulin can trigger adverse effects, so some people with diabetes rely on animal-source insulin.[87]
Unlike many medicines, insulin currently cannot be taken orally because, like nearly all other proteins introduced into the gastrointestinal tract, it is reduced to fragments, whereupon all activity is lost. There has been some research into ways to protect insulin from the digestive tract, so that it can be administered orally or sublingually.[88][89]
# History of study
## Discovery
In 1869, while studying the structure of the pancreas under a microscope, Paul Langerhans, a medical student in Berlin, identified some previously unnoticed tissue clumps scattered throughout the bulk of the pancreas.[90] The function of the "little heaps of cells", later known as the islets of Langerhans, initially remained unknown, but Édouard Laguesse later suggested they might produce secretions that play a regulatory role in digestion.[91] Paul Langerhans' son, Archibald, also helped to understand this regulatory role. The term "insulin" originates from insula, the Latin word for islet/island.
In 1889, the physician Oskar Minkowski, in collaboration with Joseph von Mering, removed the pancreas from a healthy dog to test its assumed role in digestion. On testing the urine, they found sugar, establishing for the first time a relationship between the pancreas and diabetes. In 1901, another major step was taken by the American physician and scientist Eugene Lindsay Opie, when he isolated the role of the pancreas to the islets of Langerhans: "Diabetes mellitus when the result of a lesion of the pancreas is caused by destruction of the islands of Langerhans and occurs only when these bodies are in part or wholly destroyed".[92][93][94]
Over the next two decades researchers made several attempts to isolate the islets' secretions. In 1906 George Ludwig Zuelzer achieved partial success in treating dogs with pancreatic extract, but he was unable to continue his work. Between 1911 and 1912, E.L. Scott at the University of Chicago tried aqueous pancreatic extracts and noted "a slight diminution of glycosuria", but was unable to convince his director of his work's value; it was shut down. Israel Kleiner demonstrated similar effects at Rockefeller University in 1915, but World War I interrupted his work and he did not return to it.[95]
In 1916, Nicolae Paulescu developed an aqueous pancreatic extract which, when injected into a diabetic dog, had a normalizing effect on blood-sugar levels. He had to interrupt his experiments because of World War I, and in 1921 he wrote four papers about his work carried out in Bucharest and his tests on a diabetic dog. Later that year, he published "Research on the Role of the Pancreas in Food Assimilation".[96][97]
## Extraction and purification
In October 1920, Canadian Frederick Banting concluded that the digestive secretions that Minkowski had originally studied were breaking down the islet secretion, thereby making it impossible to extract successfully. A surgeon by training, Banting knew certain arteries could be tied off that would lead most of the pancreas to atrophy, while leaving the islets of Langerhans intact. He reasoned that a relatively pure extract could be made from the islets once most of the rest of the pancreas was gone. He jotted a note to himself: "Ligate pancreatic ducts of the dog. Keep dogs alive till acini degenerate leaving islets. Try to isolate internal secretion of these and relieve glycosuria."[98]
In the spring of 1921, Banting traveled to Toronto to explain his idea to J.J.R. Macleod, Professor of Physiology at the University of Toronto. Macleod was initially skeptical, since Banting had no background in research and was not familiar with the latest literature, but he agreed to provide lab space for Banting to test out his ideas. Macleod also arranged for two undergraduates to be Banting's lab assistants that summer, but Banting required only one lab assistant. Charles Best and Clark Noble flipped a coin; Best won the coin toss and took the first shift. This proved unfortunate for Noble, as Banting kept Best for the entire summer and eventually shared half his Nobel Prize money and credit for the discovery with Best.[99] On 30 July 1921, Banting and Best successfully isolated an extract ("isleton") from the islets of a duct-tied dog and injected it into a diabetic dog, finding that the extract reduced its blood sugar by 40% in 1 hour.[100][98]
Banting and Best presented their results to Macleod on his return to Toronto in the fall of 1921, but Macleod pointed out flaws with the experimental design, and suggested the experiments be repeated with more dogs and better equipment. He moved Banting and Best into a better laboratory and began paying Banting a salary from his research grants. Several weeks later, the second round of experiments was also a success, and Macleod helped publish their results privately in Toronto that November. Bottlenecked by the time-consuming task of duct-tying dogs and waiting several weeks to extract insulin, Banting hit upon the idea of extracting insulin from the fetal calf pancreas, which had not yet developed digestive glands. By December, they had also succeeded in extracting insulin from the adult cow pancreas. Macleod discontinued all other research in his laboratory to concentrate on the purification of insulin. He invited biochemist James Collip to help with this task, and the team felt ready for a clinical test within a month.[98]
On January 11, 1922, Leonard Thompson, a 14-year-old diabetic who lay dying at the Toronto General Hospital, was given the first injection of insulin.[101] However, the extract was so impure that Thompson suffered a severe allergic reaction, and further injections were cancelled. Over the next 12 days, Collip worked day and night to improve the ox-pancreas extract. A second dose was injected on January 23, completely eliminating the glycosuria that was typical of diabetes without causing any obvious side-effects. The first American patient was Elizabeth Hughes, the daughter of U.S. Secretary of State Charles Evans Hughes.[102] The first patient treated in the U.S. was future woodcut artist James D. Havens; Dr. John Ralston Williams imported insulin from Toronto to Rochester, New York, to treat Havens.[103]
Banting and Best never worked well with Collip, regarding him as something of an interloper, and Collip left the project soon after. Over the spring of 1922, Best managed to improve his techniques to the point where large quantities of insulin could be extracted on demand, but the preparation remained impure. The drug firm Eli Lilly and Company had offered assistance not long after the first publications in 1921, and they took Lilly up on the offer in April. In November, Lilly's head chemist, George B. Walden discovered isoelectric precipitation and was able to produce large quantities of highly refined insulin. Shortly thereafter, insulin was offered for sale to the general public.
## Synthesis
Purified animal-sourced insulin was initially the only type of insulin available to diabetics. The amino acid structure of insulin was characterized in the early 1950s by Frederick Sanger,[104] and the first synthetic insulin was produced simultaneously in the labs of Panayotis Katsoyannis at the University of Pittsburgh and Helmut Zahn at RWTH Aachen University in the early 1960s.[105][106] Synthetic crystalline bovine insulin was achieved by Chinese researchers in 1965.[107]
The first genetically engineered, synthetic "human" insulin was produced using E. coli in 1978 by Arthur Riggs and Keiichi Itakura at the Beckman Research Institute of the City of Hope in collaboration with Herbert Boyer at Genentech.[7][8] Genentech, founded by Swanson, Boyer and Eli Lilly and Company, went on in 1982 to sell the first commercially available biosynthetic human insulin under the brand name Humulin.[8] The vast majority of insulin currently used worldwide is now biosynthetic recombinant "human" insulin or its analogues.[9]
Recombinant insulin is produced either in yeast (usually Saccharomyces cerevisiae) or E. coli.[108] In yeast, insulin may be engineered as a single-chain protein with a KexII endoprotease (a yeast homolog of PCI/PCII) site that separates the insulin A chain from a c-terminally truncated insulin B chain. A chemically synthesized c-terminal tail is then grafted onto insulin by reverse proteolysis using the inexpensive protease trypsin; typically the lysine on the c-terminal tail is protected with a chemical protecting group to prevent proteolysis. The ease of modular synthesis and the relative safety of modifications in that region accounts for common insulin analogs with c-terminal modifications (e.g. lispro, aspart, glulisine). The Genentech synthesis and completely chemical synthesis such as that by Bruce Merrifield are not preferred because the efficiency of recombining the two insulin chains is low, primarily due to competition with the precipitation of insulin B chain.
## Nobel Prizes
The Nobel Prize committee in 1923 credited the practical extraction of insulin to a team at the University of Toronto and awarded the Nobel Prize to two men: Frederick Banting and J.J.R. Macleod.[109] They were awarded the Nobel Prize in Physiology or Medicine in 1923 for the discovery of insulin. Banting, insisted that Best was not mentioned, shared his prize with him, and Macleod immediately shared his with James Collip. The patent for insulin was sold to the University of Toronto for one dollar.
Two other Nobel Prizes have been awarded for work on insulin. British molecular biologist Frederick Sanger determined the primary structure of insulin in 1955, making it the first protein to be sequenced.[104] Sanger was awarded the 1958 Nobel Prize in Chemistry for this work. Rosalyn Sussman Yalow received the 1977 Nobel Prize in Medicine for the development of the radioimmunoassay for insulin.
Several Nobel Prizes also have an indirect connection with insulin. George Minot, co-recipient of the 1934 Nobel Prize for the development of the first effective treatment for pernicious anemia, had diabetes mellitus. Dr. William Castle observed that the 1921 discovery of insulin, arriving in time to keep Minot alive, was therefore also responsible for the discovery of a cure for pernicious anemia.[110] Dorothy Hodgkin was awarded a Nobel Prize in Chemistry in 1964 for the development of crystallography. In 1969, after decades of work, Hodgkin determined the spatial conformation of insulin, the so-called tertiary structure, by means of X-ray diffraction studies.
### Controversy
The work published by Banting, Best, Collip and Macleod represented the preparation of purified insulin extract suitable for use on human patients.[111] Although Paulescu discovered the principles of the treatment, his saline extract could not be used on humans; he was not mentioned in the 1923 Nobel Prize. Professor Ian Murray was particularly active in working to correct "the historical wrong" against Nicolae Paulescu. Murray was a professor of physiology at the Anderson College of Medicine in Glasgow, Scotland, the head of the department of Metabolic Diseases at a leading Glasgow hospital, vice-president of the British Association of Diabetes, and a founding member of the International Diabetes Federation. Murray wrote:
Insufficient recognition has been given to Paulescu, the distinguished Romanian scientist, who at the time when the Toronto team were commencing their research had already succeeded in extracting the antidiabetic hormone of the pancreas and proving its efficacy in reducing the hyperglycaemia in diabetic dogs.[112]
In a private communication, Professor Arne Tiselius, former head of the Nobel Institute, expressed his personal opinion that Paulescu was equally worthy of the award in 1923.[113] | https://www.wikidoc.org/index.php/Apidra_OptiClik_Cartridge | |
7fe2ea3e5b165a30f4038a679352f9948a19fc1b | wikidoc | Applera | Applera
Applera Corporation of Norwalk, Connecticut, at #874 on the 2007 Fortune 1000 list, is one of the largest international biotechnology companies based in the United States. It is the successor company to what was the Life Sciences Division of Perkin-Elmer Corporation. Applera is not publicly-traded, but instead it consists of two major groups which are publicly-traded tracking stocks in the proteomics industrial sector. These two groups are the S&P 500 listed Applera Corp-Applied Biosystems Group (Template:Nyse2) of Foster City, California, and Applera Corp-Celera Genomics Group (Template:Nyse2) of Rockville, Maryland.
As the former Perkin-Elmer (formerly Template:Nyse2), Applera had a history dating back to 1931. But more precisely, its history dates from 1999, when Perkin-Elmer effectively split in half, and sold off its more tradional half of the business to EG&G Inc. (formely Template:Nyse2). As part of the deal, it also sold the Perkin-Elmer name, because that most properly associated with that tradional line of products, and EG&G then became the new PerkinElmer (Template:Nyse2). At that point the remaining Conecticut Life Sciences company issued its two tracking stocks, and also changed its own name to PE Corporation. The Applied Biosystems group had earlier already been renamed PE Biosystems, and it retained that name in the first incarnation of its tracking stock (formerly Template:Nyse2). In 2000, the Applied Biosystems name was restored to the group, with the new stock ticker symbol ABI, and PE Corporation became Applera, a combination of its two components' names, Appl(iedCel)era.
# Board of Directors
The Applera Corporation Directors oversee the parent corporation along with the operations of both tracking stock groups, and consequently they have the responsibilty of fairly balancing the interests of both groups of investors in each stock.
- Joseph F. Abely, Jr., Director since 1984, retired Chairman and CEO of Sea-Land Corporation
- Robert H. Hayes, Ph.D., Director since 1985, Philip Caldwell Professor at Harvard Business School
- Richard H. Ayers, Director since 1988, retired Chairman and CEO of The Stanley Works
- Jean-Luc Bélingard, Director since 1993, CEO of Pierre Fabre S.A.
- Carolyn W. Slayman, Ph.D., Director since 1994, Sterling Professor and Deputy Dean of Yale University School of Medicine
- Orin R. Smith, Director since 1995, Chairman and CEO of Engelhard Corporation
- Tony L. White, Director since 1995, Chairman, President and CEO of Applera Corporation
- Georges C. St. Laurent, Jr., Director since 1996, principal of St. Laurent Properties and former CEO of Western Bank
- Arnold J. Levine, Ph.D., Director since 1999, President and CEO of Rockefeller University
- Theodore E. Martin, Director since 1999, retired President and CEO of Barnes Group Inc.
- James R. Tobin, Director since 1999, President and CEO of Boston Scientific Corporation
# History
The original Perkin-Elmer, and then its successor PE Corporation and Applera Corporation have been headquarted in Norwalk, Connecticut. The company address is at 50 Danbury Rd.
In the early 1990s, Perkin-Elmer, which had been a maker of diverse electronic instruments and analytical and optical equipment, established strong ties with groups closely involved with the business of decoding the human genome. By the late 1990s, Perkin-Elmer's Life Sciences division had become centrally involved in highly-publicized intense competition against the public consortium that was also working on the massive task. Consequently Perkin-Elmer's people and companies became among the most famous players of the decade in biotechnology and in that segment of the technology bubble. In the process, Perkin-Elmer divided and transformed itself into Applera, a company entirely focused in life sciences.
Beginning in 1990, the U.S. government approved financing to support the Human Genome Project (HGP). Dr. James D. Watson, who founded the public consortium, forecast that the project could be completed in 15 years from its 1990 starting date, at a cost of US$3 billion. The HGP was a public consortium of eight university centers funded through the U.S. Department of Energy, the National Institutes of Health and the Wellcome Trust of London. The government-backed project targeted completion of human DNA mapping by the year 2005.
In 1993, Perkin-Elmer acquired a key equipment maker, Applied Biosystems, Inc., and that stock's symbol ABIO ceased trading on the NASDAQ exchange, as it became a division of Perkin-Elmer. Michael W. Hunkapiller, Ph.D., who had been Applied Biosystem's Chairman, President and CEO since 1983, became a Senior Vice President of Perkin-Elmer, and President of the Applied and PE Biosystems Divisions.
In 1994, Perkin-Elmer reported net revenues of over $1 billion, of which Life Sciences accounted for 42% of the business. The company has 5,954 employees. The new competitive genomics industry had formed for the development of new pharmaceuticals, based on the work of the Human Genome Project. The Applied Biosystems Division made thermal cyclers and automated sequencers for these new genomics companies.
In 1995, Perkin-Elmer sold its 30,000th thermal cycler. To meet Human Genome Project goals, Perkin-Elmer developed mapping kits with markers every 10 million bases along each chromosome. Also that year, DNA fingerprinting using polymerase chain reaction (PCR) became accepted in court as reliable forensic evidence. In 1993, Perkin-Elmer had become the world's leading manufacturer of instruments and reagents for (PCR). It marketed PCR reagents kits in alliance with Hoffman-La Roche Inc.
In 1996, Perkin-Elmer acquired Tropix, Inc., a chemiluminescence company, for its life sciences division.
## PE Applied Biosystems Division
Also In 1996, Tony L. White from Baxter International Inc. became President and Chief Executive Officer of Perkin-Elmer and reorganized it into two separate operating divisions, Analytical Instruments and PE Applied Biosystems. The PE Applied Biosystems division accounted for half of Perkin-Elmer's total revenue, with net revenues up by 26%.
In 1997, Perkin-Elmer revenues reached almost US$1.3 billion, of which PE Applied Biosystems was US$653 million. Acquisitions included GenScope, Inc., and Linkage Genetics, Inc., which combined with Zoogen to form PE AgGen, focused on genetic analysis services for plant and animal breeding. Partnerships were begun with Hyseq, Inc., on the new DNA chip technology, and also with Tecan U.S., Inc., on combinatorial chemistry automation systems, and also with Molecular Informatics, Inc. on genetic data management and analysis automated systems.
In 1998, Perkin-Elmer acquired PerSeptive Biosystems (formerly Template:Nasdaq2), a leader in the bio-instrumentation field where it made biomolecule purification systems for protein analysis. Noubar B. Afeyan, Ph.D., had been the founder, Chairman, and CEO of PerSeptive, and after the acquisition he became a Senior Vice President and Chief Business Officer of Perkin-Elmer. He had earlier founded and co-built several successful life science and technology startup companies through the 1990s, after earning his Ph.D. in Biochemical Engineering from the Massachusetts Institute of Technology in 1987.
## PE Biosystems Division
In 1998, Perkin-Elmer formed the the PE Biosystems division, by consoliding Applied Biosystems, PerSeptive Biosystems, Tropix and PE Informatics. Informatics was formed from the Perkin-Elmer combination of two other acquisitions, Molecular Informatics and Nelson Analytical Systems, with existing units of Perkin-Elmer.
By 1998, Perkin-Elmer had a presence on the World Wide Web at .
While planning the next new generation of machines, PE Biosystems' president, Michael W. Hunkapiller, calculated that it would be possible for their own private industry to decode the human genome before the academic consortium could complete it. The company would decode all of the 3.5 billion chemical letters in the human DNA by 2001, at a cost of only US$200 million, about 1/10th of the consortium projected cost of US$3 billion. However, it would mean starting from scratch, eight years already into the consortium's program. It was a bold prediction, given that the consortium target date set by Dr. Watson back in 1990 had been the forward year of 2005, only seven years away, and with the consortium already half the way to the completion target date by then.
Also, it meant that Dr. Hunkapiller's idea would require competing against his own customers, to all of whom Applied Biosystems sold its sequencing machines and their chemical reagents. However, he calculated that it would also mean doubling the market for that equipment.
Hunkapiller brought in Dr. J. Craig Venter to direct the project. Tony L. White, president of the Perkin-Elmer Corporation backed Hunkapiller on the venture. Perkin-Elmer's interest was driven largely by its monopoly, through the equipment of Applied Biosystems, of the market for automated DNA sequencing machines. Dr. Venter boldy declared to the media that he would complete the genome decoding by 2001. That bold pronouncement prompted the academic consortium to accelerate their own deadline by a couple years, to 2003.
In May 1998, the company's newly formed unit to accomplish the task, Celera Genomics Group, in Rockville, Maryland, was created to become the definitive source of genomic and related medical information with the goal of sequencing the human genome by the year 2001. Celera became the primary commercial competitor to the government-funded effort of the Human Genome Project. Venter became President and Chief Scientific Officer of Celera.
At the time, Venter operated his own independent lab, The Institute for Genomic Research (TIGR), which had developed a "random shotgun" approach to DNA decoding, making it the most prolific genome lab in the world.
At year end 1998, the PE Biosystems Group's sales reached US$940 million. Its chief new genomics instrument was the ABI PRISM® 3700 DNA Analyzer, which it had developed in conjunction with Hitachi, Ltd. The new machine, an electrophoresis-based genetic analysis system, cost US$300,000 each, but was a major leap beyond its predecessor, the 377, and was fully automated, allowing genetic decoding to run around the clock with little supervision. According to Venter, the machine was so revolutionary that it could decode in a single day the same amount of genetic material that most DNA labs could produce in a year.
The partnership sold hundreds of the 3700 analyzers to Celera, and also to others worldwide. The public consortium also bought one of the Applied Biosytems 3700 sequencers, and had plans to buy 200 more. The machine proved to be so fast that by late March 1999 the consortium announced that it had revised its timeline, and would release by the Spring of 2000 a "first draft sequence" for 80% of the human genome.
## PE Corporation
On March 19, 1999 Perkin-Elmer Corporation, as a New York corporation, filed SEC Form S-4/A, to enter a reincorporation merger with a subsidiary of PE Corporation of Delaware. Shareholders of the New York corporation stock (NYSE:PKN) would receive shares in two new stocks instead.
On April 27, 1999, the shareholders of Perkin-Elmer Corporation approved the reorganization of Perkin-Elmer into a pure-play life science company, resulting in the name change to PE Corporation and the de-listing of the PKN stock. Each share of the Perkin-Elmer New York (PKN) was to be exchanged for one share and for ½ of a share respectively of the two new common share tracking stocks for the two component Life Sciences groups, PE Biosystems Group (NYSE:PEB) and Celera Genomics Group (NYSE:CRA). (PKN now)
On April 28, 1999, the two replacement tracking stocks for the new PE Corporation were issued to shareholders. The Pacific Stock Exchange began trading PE Corporation options for the two new stocks that day. Dr. Michael W. Hunkapiller remained as Senior Vice President of PE Corporation, and as president of PE Biosystems. Dr. Afeyan initiated and oversaw the creation of the tracking stock for Celera Genomics Group. Then later in 1999 Dr. Afeyan left, to co-found Flagship Ventures, an early stage entrepreneurial venture capital firm. Dr. J. Craig Venter remained as Senior Vice President of PE Corporation and also President of Celera Genomics Group. Tony L. White remained as PE Corporation's Chairman, President and Chief Executive Officer.
Other officers who remained in PE Corporation included William B. Sawch, as Senior Vice President, General Counsel and Secretary.
On May 6, 1999,the reorganization was made effective, as the Perkin-Elmer Corporation was merged into a temporarily created subsidiary of PE Corporation, a new Delaware corporation. The recapitalization of the company resulted in issuance of the two new classes of common stock, called PE Corporation-PE Biosystems Group Common Stock and PE Corporation-Celera Genomics Group Common Stock. On that date, trading began in both new stocks on the New York Stock Exchange, to great excitement.
On May 28, 1999 as part of the recapitalization and reorganization, the company completed the sale of its traditional business unit, the Analytical Instruments Division to EG&G Inc., along with the Perkin-Elmer name, for US$425 million. EG&G was based in Wellesley, Massachusetts, and made products for diverse industries including automotive, medical, aerospace and photography. On July 14, 1999 that new analytical instruments maker PerkinElmer cut 350 jobs, or 12%, in its cost reduction reorganization.
On June 17, 1999 the Board of PE Corporation announced a two-for-one split of PE Biosystems Group Common Stock.
At year end 1999, after the major divestment that year of the former Analytical Instruments Division, the new PE Corporation assets totalled over US$1.5 billion, split between the two Life Sciences groups. Of that, PE Biosystems Group, with 3,500 employees had net revenues of over US$1.2 billion.
By June 2000, the genomics segment of the technology bubble was peaking. Celera Genomics (CRA) and PE Biosystems (PEB) were among among five genetics pioneers leading at that time, along with Incyte Genomics (Template:Nasdaq2), Human Genome Sciences (Template:Nasdaq2), and Millennium Pharmaceuticals (Template:Nasdaq2). All five of those stocks by then had exceeded a price above $100 a share in the market, before ultimately crashing back down.
## Applera
On November 28, 2000 PE Corporation filed SEC Form 8-K to report its announcement of the change of its name to Applera Corporation. At the same time, PE Biosystems Group changed its name to Applied Biosystems Group, and changed its ticker symbol from PEB to ABI. Both name changes became effective November 30, 2000. Also that date, the parent corporation web site address changed from to .
The combined Applera then had 5,000 employees. PE/Applied Biosystems Group's net revenues rose to almost US$1.4 billion. Celera that year made milestone headlines when it announced that it had completed the sequencing and first assembly of the two largest genomes in history, that of the fruit fly, and of the human.
In 2001, the Applied Biosystems division of Applera reached revenues of US$1.6 billion, and developed a new workstation instrument specifically for the new field of proteomics, which had become Celera's new core business focus, as it shifted away from gene discovery. The instrument analyzed 1,000 protein samples per hour.
In January 2002, J. Craig Venter was pushed out of Celera, when it was decided that the group would make pharmaceuticals instead. Venter lacked experience in pharmaceutical development.
On April 22, 2002, the Celera Genomics Group announced its decision to abandon what had been its core business since its 1998 inception, and to shift the role of marketing data from its genetic database over to its sister company, the Applied Biosystems Group. Celera would instead develop pharmaceutical drugs. Applera CEO Tony L. White had noted earlier that the database business would distract from pharmaceutical development.
Applied Biosystems was a better fit for the database, because Applied already had the huge sales force in place for the marketing of its instruments. Plans were to expand those sales and those of the database into an electronic commerce system.
The database itself, Celera Discovery System™ (CDS), would remain with Celera, because of shareholder approval complications. Celera would retain responsibilty for its maintenance and support to existing customers, and would receive royalties from Applied Biosystems. The database revenues were expected to reach US$100 million for the June fiscal year end, which would be its first profitable year. But it had always faced the problem that its public competitor, the consortium project, provides free data from its own database.
In 2002, Applied Biosystems Group again posted revenues of US$1.6 billion for the year.
In 2004, the long-term Applied Biosystems president, Mike Hunkapiller, retired and Cathy Burzik, who had joined the Group in 2003, replaced him as President of Applied Biosystems Group. | Applera
Applera Corporation of Norwalk, Connecticut, at #874 on the 2007 Fortune 1000 list, is one of the largest international biotechnology companies based in the United States. It is the successor company to what was the Life Sciences Division of Perkin-Elmer Corporation. Applera is not publicly-traded, but instead it consists of two major groups which are publicly-traded tracking stocks in the proteomics industrial sector. These two groups are the S&P 500 listed Applera Corp-Applied Biosystems Group (Template:Nyse2) of Foster City, California, and Applera Corp-Celera Genomics Group (Template:Nyse2) of Rockville, Maryland.
As the former Perkin-Elmer (formerly Template:Nyse2), Applera had a history dating back to 1931. But more precisely, its history dates from 1999, when Perkin-Elmer effectively split in half, and sold off its more tradional half of the business to EG&G Inc. (formely Template:Nyse2). As part of the deal, it also sold the Perkin-Elmer name, because that most properly associated with that tradional line of products, and EG&G then became the new PerkinElmer (Template:Nyse2). At that point the remaining Conecticut Life Sciences company issued its two tracking stocks, and also changed its own name to PE Corporation. The Applied Biosystems group had earlier already been renamed PE Biosystems, and it retained that name in the first incarnation of its tracking stock (formerly Template:Nyse2). In 2000, the Applied Biosystems name was restored to the group, with the new stock ticker symbol ABI, and PE Corporation became Applera, a combination of its two components' names, Appl(iedCel)era.[1]
# Board of Directors
The Applera Corporation Directors oversee the parent corporation along with the operations of both tracking stock groups, and consequently they have the responsibilty of fairly balancing the interests of both groups of investors in each stock.[2] [3]
- Joseph F. Abely, Jr., Director since 1984, retired Chairman and CEO of Sea-Land Corporation
- Robert H. Hayes, Ph.D., Director since 1985, Philip Caldwell Professor at Harvard Business School
- Richard H. Ayers, Director since 1988, retired Chairman and CEO of The Stanley Works
- Jean-Luc Bélingard, Director since 1993, CEO of Pierre Fabre S.A.
- Carolyn W. Slayman, Ph.D., Director since 1994, Sterling Professor and Deputy Dean of Yale University School of Medicine
- Orin R. Smith, Director since 1995, Chairman and CEO of Engelhard Corporation
- Tony L. White, Director since 1995, Chairman, President and CEO of Applera Corporation
- Georges C. St. Laurent, Jr., Director since 1996, principal of St. Laurent Properties and former CEO of Western Bank
- Arnold J. Levine, Ph.D., Director since 1999, President and CEO of Rockefeller University
- Theodore E. Martin, Director since 1999, retired President and CEO of Barnes Group Inc.
- James R. Tobin, Director since 1999, President and CEO of Boston Scientific Corporation
# History
The original Perkin-Elmer, and then its successor PE Corporation and Applera Corporation have been headquarted in Norwalk, Connecticut. The company address is at 50 Danbury Rd.[1]
In the early 1990s, Perkin-Elmer, which had been a maker of diverse electronic instruments and analytical and optical equipment,[4] established strong ties with groups closely involved with the business of decoding the human genome. By the late 1990s, Perkin-Elmer's Life Sciences division had become centrally involved in highly-publicized intense competition against the public consortium that was also working on the massive task. Consequently Perkin-Elmer's people and companies became among the most famous players of the decade in biotechnology and in that segment of the technology bubble. In the process, Perkin-Elmer divided and transformed itself into Applera, a company entirely focused in life sciences.
Beginning in 1990, the U.S. government approved financing to support the Human Genome Project (HGP). Dr. James D. Watson, who founded the public consortium, forecast that the project could be completed in 15 years from its 1990 starting date, at a cost of US$3 billion.[5] The HGP was a public consortium of eight university centers funded through the U.S. Department of Energy, the National Institutes of Health and the Wellcome Trust of London. The government-backed project targeted completion of human DNA mapping by the year 2005.[6]
In 1993, Perkin-Elmer acquired a key equipment maker, Applied Biosystems, Inc., and that stock's symbol ABIO ceased trading on the NASDAQ exchange, as it became a division of Perkin-Elmer. Michael W. Hunkapiller, Ph.D., who had been Applied Biosystem's Chairman, President and CEO since 1983,[5] became a Senior Vice President of Perkin-Elmer, and President of the Applied and PE Biosystems Divisions.[7]
In 1994, Perkin-Elmer reported net revenues of over $1 billion, of which Life Sciences accounted for 42% of the business. The company has 5,954 employees. The new competitive genomics industry had formed for the development of new pharmaceuticals, based on the work of the Human Genome Project. The Applied Biosystems Division made thermal cyclers and automated sequencers for these new genomics companies.[8]
In 1995, Perkin-Elmer sold its 30,000th thermal cycler. To meet Human Genome Project goals, Perkin-Elmer developed mapping kits with markers every 10 million bases along each chromosome. Also that year, DNA fingerprinting using polymerase chain reaction (PCR) became accepted in court as reliable forensic evidence. In 1993, Perkin-Elmer had become the world's leading manufacturer of instruments and reagents for (PCR). It marketed PCR reagents kits in alliance with Hoffman-La Roche Inc.[8]
In 1996, Perkin-Elmer acquired Tropix, Inc., a chemiluminescence company, for its life sciences division.[1]
## PE Applied Biosystems Division
Also In 1996, Tony L. White from Baxter International Inc. became President and Chief Executive Officer of Perkin-Elmer and reorganized it into two separate operating divisions, Analytical Instruments and PE Applied Biosystems. The PE Applied Biosystems division accounted for half of Perkin-Elmer's total revenue, with net revenues up by 26%.[8]
In 1997, Perkin-Elmer revenues reached almost US$1.3 billion, of which PE Applied Biosystems was US$653 million. Acquisitions included GenScope, Inc., and Linkage Genetics, Inc., which combined with Zoogen to form PE AgGen, focused on genetic analysis services for plant and animal breeding. Partnerships were begun with Hyseq, Inc., on the new DNA chip technology, and also with Tecan U.S., Inc., on combinatorial chemistry automation systems, and also with Molecular Informatics, Inc. on genetic data management and analysis automated systems.[8]
In 1998, Perkin-Elmer acquired PerSeptive Biosystems (formerly Template:Nasdaq2), a leader in the bio-instrumentation field where it made biomolecule purification systems for protein analysis.[1] [4] [9] Noubar B. Afeyan, Ph.D., had been the founder, Chairman, and CEO of PerSeptive, and after the acquisition he became a Senior Vice President and Chief Business Officer of Perkin-Elmer. He had earlier founded and co-built several successful life science and technology startup companies through the 1990s, after earning his Ph.D. in Biochemical Engineering from the Massachusetts Institute of Technology in 1987.[9]
## PE Biosystems Division
In 1998, Perkin-Elmer formed the the PE Biosystems division, by consoliding Applied Biosystems, PerSeptive Biosystems, Tropix and PE Informatics. Informatics was formed from the Perkin-Elmer combination of two other acquisitions, Molecular Informatics and Nelson Analytical Systems, with existing units of Perkin-Elmer.[1]
By 1998, Perkin-Elmer had a presence on the World Wide Web at http://www.perkin-elmer.com.[10]
While planning the next new generation of machines, PE Biosystems' president, Michael W. Hunkapiller, calculated that it would be possible for their own private industry to decode the human genome before the academic consortium could complete it. The company would decode all of the 3.5 billion chemical letters in the human DNA by 2001, at a cost of only US$200 million, about 1/10th of the consortium projected cost of US$3 billion.[6] However, it would mean starting from scratch, eight years already into the consortium's program.[5] It was a bold prediction, given that the consortium target date set by Dr. Watson back in 1990 had been the forward year of 2005, only seven years away, and with the consortium already half the way to the completion target date by then.
Also, it meant that Dr. Hunkapiller's idea would require competing against his own customers, to all of whom Applied Biosystems sold its sequencing machines and their chemical reagents. However, he calculated that it would also mean doubling the market for that equipment.[5]
Hunkapiller brought in Dr. J. Craig Venter to direct the project. Tony L. White, president of the Perkin-Elmer Corporation backed Hunkapiller on the venture. Perkin-Elmer's interest was driven largely by its monopoly, through the equipment of Applied Biosystems, of the market for automated DNA sequencing machines. Dr. Venter boldy declared to the media that he would complete the genome decoding by 2001.[6] [10] That bold pronouncement prompted the academic consortium to accelerate their own deadline by a couple years, to 2003.[5]
In May 1998, the company's newly formed unit to accomplish the task, Celera Genomics Group, in Rockville, Maryland, was created to become the definitive source of genomic and related medical information with the goal of sequencing the human genome by the year 2001.[10] Celera became the primary commercial competitor to the government-funded effort of the Human Genome Project. Venter became President and Chief Scientific Officer of Celera. [6]
At the time, Venter operated his own independent lab, The Institute for Genomic Research (TIGR), which had developed a "random shotgun" approach to DNA decoding, making it the most prolific genome lab in the world.[6]
At year end 1998, the PE Biosystems Group's sales reached US$940 million. Its chief new genomics instrument was the ABI PRISM® 3700 DNA Analyzer, which it had developed in conjunction with Hitachi, Ltd.[10] The new machine, an electrophoresis-based genetic analysis system, cost US$300,000 each, but was a major leap beyond its predecessor, the 377, and was fully automated, allowing genetic decoding to run around the clock with little supervision.[8] According to Venter, the machine was so revolutionary that it could decode in a single day the same amount of genetic material that most DNA labs could produce in a year.[6]
The partnership sold hundreds of the 3700 analyzers to Celera, and also to others worldwide.[8] The public consortium also bought one of the Applied Biosytems 3700 sequencers, and had plans to buy 200 more. The machine proved to be so fast that by late March 1999 the consortium announced that it had revised its timeline, and would release by the Spring of 2000 a "first draft sequence" for 80% of the human genome.[6]
## PE Corporation
On March 19, 1999 Perkin-Elmer Corporation, as a New York corporation, filed SEC Form S-4/A, to enter a reincorporation merger with a subsidiary of PE Corporation of Delaware. Shareholders of the New York corporation stock (NYSE:PKN) would receive shares in two new stocks instead.[11]
On April 27, 1999,[6] the shareholders of Perkin-Elmer Corporation approved the reorganization of Perkin-Elmer into a pure-play life science company,[12] resulting in the name change to PE Corporation and the de-listing of the PKN stock. Each share of the Perkin-Elmer New York (PKN) was to be exchanged for one share and for ½ of a share respectively of the two new common share tracking stocks for the two component Life Sciences groups, PE Biosystems Group (NYSE:PEB) and Celera Genomics Group (NYSE:CRA).[10] [11] (PKN now)[13]
On April 28, 1999, the two replacement tracking stocks for the new PE Corporation were issued to shareholders.[12] The Pacific Stock Exchange began trading PE Corporation options for the two new stocks that day. [6] Dr. Michael W. Hunkapiller remained as Senior Vice President of PE Corporation, and as president of PE Biosystems.[10] Dr. Afeyan initiated and oversaw the creation of the tracking stock for Celera Genomics Group.[9] Then later in 1999 Dr. Afeyan left, to co-found Flagship Ventures, an early stage entrepreneurial venture capital firm.[9] Dr. J. Craig Venter remained as Senior Vice President of PE Corporation and also President of Celera Genomics Group. Tony L. White remained as PE Corporation's Chairman, President and Chief Executive Officer.[7]
Other officers who remained in PE Corporation included William B. Sawch, as Senior Vice President, General Counsel and Secretary.[7]
On May 6, 1999,the reorganization was made effective, as the Perkin-Elmer Corporation was merged into a temporarily created subsidiary of PE Corporation, a new Delaware corporation. The recapitalization of the company resulted in issuance of the two new classes of common stock, called PE Corporation-PE Biosystems Group Common Stock and PE Corporation-Celera Genomics Group Common Stock.[14] On that date, trading began in both new stocks on the New York Stock Exchange, to great excitement.[6]
On May 28, 1999 as part of the recapitalization and reorganization, the company completed the sale of its traditional business unit, the Analytical Instruments Division to EG&G Inc., along with the Perkin-Elmer name, for US$425 million.[15] [16] EG&G was based in Wellesley, Massachusetts, and made products for diverse industries including automotive, medical, aerospace and photography. On July 14, 1999 that new analytical instruments maker PerkinElmer cut 350 jobs, or 12%, in its cost reduction reorganization.[16]
On June 17, 1999 the Board of PE Corporation announced a two-for-one split of PE Biosystems Group Common Stock.[14]
At year end 1999, after the major divestment that year of the former Analytical Instruments Division, the new PE Corporation assets totalled over US$1.5 billion, split between the two Life Sciences groups.[14] Of that, PE Biosystems Group, with 3,500 employees had net revenues of over US$1.2 billion.[8]
By June 2000, the genomics segment of the technology bubble was peaking. Celera Genomics (CRA) and PE Biosystems (PEB) were among among five genetics pioneers leading at that time, along with Incyte Genomics (Template:Nasdaq2), Human Genome Sciences (Template:Nasdaq2), and Millennium Pharmaceuticals (Template:Nasdaq2). All five of those stocks by then had exceeded a price above $100 a share in the market, before ultimately crashing back down.[17]
## Applera
On November 28, 2000 PE Corporation filed SEC Form 8-K to report its announcement of the change of its name to Applera Corporation. At the same time, PE Biosystems Group changed its name to Applied Biosystems Group, and changed its ticker symbol from PEB to ABI. Both name changes became effective November 30, 2000. Also that date, the parent corporation web site address changed from http://www.pecorporation.com to http://www.applera.com.[1]
The combined Applera then had 5,000 employees. PE/Applied Biosystems Group's net revenues rose to almost US$1.4 billion. Celera that year made milestone headlines when it announced that it had completed the sequencing and first assembly of the two largest genomes in history, that of the fruit fly, and of the human.[8]
In 2001, the Applied Biosystems division of Applera reached revenues of US$1.6 billion, and developed a new workstation instrument specifically for the new field of proteomics, which had become Celera's new core business focus, as it shifted away from gene discovery. The instrument analyzed 1,000 protein samples per hour.[8]
In January 2002, J. Craig Venter was pushed out of Celera, when it was decided that the group would make pharmaceuticals instead. Venter lacked experience in pharmaceutical development.[3]
On April 22, 2002, the Celera Genomics Group announced its decision to abandon what had been its core business since its 1998 inception, and to shift the role of marketing data from its genetic database over to its sister company, the Applied Biosystems Group. Celera would instead develop pharmaceutical drugs. Applera CEO Tony L. White had noted earlier that the database business would distract from pharmaceutical development.[3]
Applied Biosystems was a better fit for the database, because Applied already had the huge sales force in place for the marketing of its instruments. Plans were to expand those sales and those of the database into an electronic commerce system.[3]
The database itself, Celera Discovery System™ (CDS),[8] would remain with Celera, because of shareholder approval complications. Celera would retain responsibilty for its maintenance and support to existing customers, and would receive royalties from Applied Biosystems. The database revenues were expected to reach US$100 million for the June fiscal year end, which would be its first profitable year. But it had always faced the problem that its public competitor, the consortium project, provides free data from its own database.[3]
In 2002, Applied Biosystems Group again posted revenues of US$1.6 billion for the year.[8]
In 2004, the long-term Applied Biosystems president, Mike Hunkapiller, retired and Cathy Burzik, who had joined the Group in 2003, replaced him as President of Applied Biosystems Group.[8] | https://www.wikidoc.org/index.php/Applera | |
226eacd1596a9d9ae71461977e474002b94cfecd | wikidoc | Apraxia | Apraxia
Synonyms and keywords: Dyspraxia
# Overview
Praxis, a Greek work for act, work, or deed, is the ability to perform the learned movements. It usually comprises of three components, namely, ideation (what to do), motor planning (how to do), and execution (performing the movement correctly), that results in purposeful movements. Apraxia, however, is the inability to execute these skilled and learned purposeful movements when there is a breakdown in any component of praxis. This disorder makes it difficult to perform daily tasks and negatively impact the quality of life. Apraxia, a complex neurological disorder, with cognitive-motor dysfunction may be acquired or developmental. It can occur as a result of brain trauma/disease, and higher motor functional neuronal pathways damage in the setting of preserved comprehension, coordination, motivation, and elementary sensory and motor systems. The most common types of apraxia are 'Ideational' and 'Ideomotor'.
# Historical Perspective
- Steinthal introduced the term apraxiae (Greek word meaning inaction) in 1871. However, a German physician, Hugo Lipmann first established the conceptual knowledge and published complete description of apraxia after studying the gestures in a 48-year old stroke patient who had a left hemispheric stroke.
- Lipmann noticed that, despite of resolution of the paresis, the patient was unable to perform tasks such as buttoning the shirt, with no affect on spontaneous movements, and doing simple tasks on command. He observed this phenomenon specifically in patients with left hemispheric lesions. He also concluded that the planning of the motor movements occurs in the motor area of the left side of the brain. Lipmann further proposed that the 'praxis' information flows from the posterior brain areas (parietal and occipital lobes) to the anterior (motor cortex).
- The major subtypes classified by Lipmann were ideational, ideomotor, and limb-kinetic apraxia.
- One of the behavioral neurologist, Norman Geschwind, presented that the superior longitudinal fasciculus involvement disconnects the Wernicke's area are from the left premotor cortex, leading to 'apraxia'
# Classification
- Ideomotor apraxia:
Most common type of apraxia.
Decreased performance of skilled motor performances despite integral language, sensory and motor function.
Seen more frequently in neurodegenerative disorders and stroke patients.
It can be classically demonstrated when a patient questioned verbally to make a motion with a limb. Patients with Ideomotor apraxia display spatial and temporal errors, inconvenient timing, amplitude, sequencing, configuration, limb position in space.
It is an inability to carry out, learned motor acts, command, adequate motor, and sensory abilities.
Ideomotor apraxia can be due to cerebral damage in numerous areas, including the left parietal lobe, the intrahemispheric association fibers, the dominant hemisphere motor association cortex, and the anterior corpus callosum.
Patients often use their arm as an object relatively than indicating how to use the object . Patients are frequently able to achieve the same acts without struggle in their daily lives. This process has been called the "voluntary-automatic dissociation".
These patients have a deficiency in their skill to plan or ample motor actions that depend on semantic memory. They can describe how to achieve a response, but incapable to "imagine" or do the movement. Though the capability to perform an act inevitably when cued remains complete, this is recognized as automatic-voluntary dissociation.In Ideomotor apraxia, there is difficulty or inability to execute familiar or learned movements on command despite of understanding the command and willingness to perform that action. The characteristic of this type of apraxia is the inability to a transitive movement. For example, the person can describe how a tool such as comb is used, but, when asked to use that tool, he is unable to perform the task (i.e. combing the hair) using the comb
- Most common type of apraxia.
- Decreased performance of skilled motor performances despite integral language, sensory and motor function.
- Seen more frequently in neurodegenerative disorders and stroke patients.
- It can be classically demonstrated when a patient questioned verbally to make a motion with a limb. Patients with Ideomotor apraxia display spatial and temporal errors, inconvenient timing, amplitude, sequencing, configuration, limb position in space.
- It is an inability to carry out, learned motor acts, command, adequate motor, and sensory abilities.
- Ideomotor apraxia can be due to cerebral damage in numerous areas, including the left parietal lobe, the intrahemispheric association fibers, the dominant hemisphere motor association cortex, and the anterior corpus callosum.
- Patients often use their arm as an object relatively than indicating how to use the object . Patients are frequently able to achieve the same acts without struggle in their daily lives. This process has been called the "voluntary-automatic dissociation".
- These patients have a deficiency in their skill to plan or ample motor actions that depend on semantic memory. They can describe how to achieve a response, but incapable to "imagine" or do the movement. Though the capability to perform an act inevitably when cued remains complete, this is recognized as automatic-voluntary dissociation.In Ideomotor apraxia, there is difficulty or inability to execute familiar or learned movements on command despite of understanding the command and willingness to perform that action. The characteristic of this type of apraxia is the inability to a transitive movement. For example, the person can describe how a tool such as comb is used, but, when asked to use that tool, he is unable to perform the task (i.e. combing the hair) using the comb
- Ideational apraxia:
As the name depicts, the problem is in conceptualization of the task.
The person may be able to name the objects correctly but fails to coceptualize how that object is used.
Inability to create a plan for or idea of a specific movement, for example, "pick up this pen and write down your name"
- As the name depicts, the problem is in conceptualization of the task.
- The person may be able to name the objects correctly but fails to coceptualize how that object is used.
- Inability to create a plan for or idea of a specific movement, for example, "pick up this pen and write down your name"
- Constructional apraxia:
It is a condition resulting from neurological damage, which is demonstrated by the inability to construct and copy to command two- and three-dimensional stimuli.
Constructional apraxia has been a classic sign of a parietal lobe lesion, and as a valuable tool to escalate the spatial abilities functioned by this lobe.
It has become gradually clear that Constructional apraxia is a complex construct that can be observed with very different tasks that are only slightly interrelated, and hit various kinds of visuospatial, attentional, perceptual, planning, and motor mechanisms.
The patient with constructional apraxia is unable to construct, draw, or copy simple configurations; for example, intersecting shapes; they have trouble drawing basic shapes or copying a simple diagram.
inability to draw or construct simple configurations
- It is a condition resulting from neurological damage, which is demonstrated by the inability to construct and copy to command two- and three-dimensional stimuli.
- Constructional apraxia has been a classic sign of a parietal lobe lesion, and as a valuable tool to escalate the spatial abilities functioned by this lobe.
- It has become gradually clear that Constructional apraxia is a complex construct that can be observed with very different tasks that are only slightly interrelated, and hit various kinds of visuospatial, attentional, perceptual, planning, and motor mechanisms.
- The patient with constructional apraxia is unable to construct, draw, or copy simple configurations; for example, intersecting shapes; they have trouble drawing basic shapes or copying a simple diagram.
- inability to draw or construct simple configurations
- Buccofacial or orofacial apraxia:
These patients cannot convey facial movements on requests, such as voluntary movements of the tongue, cheeks, lips, pharynx, or larynx on command, for example, include licking lips, whistling, coughing, or winking).
- These patients cannot convey facial movements on requests, such as voluntary movements of the tongue, cheeks, lips, pharynx, or larynx on command, for example, include licking lips, whistling, coughing, or winking).
- Limb-kinetic apraxia:
It is the failure to make precise movements with an arm, finger, or leg. For example, a person may have trouble tying their shoes, waving hello, or typing on a computer.
Inability to make fine, precise movements with a limb
- It is the failure to make precise movements with an arm, finger, or leg. For example, a person may have trouble tying their shoes, waving hello, or typing on a computer.
- Inability to make fine, precise movements with a limb
- Gait apraxia:
Apraxia of gait is a rare locomotion syndrome categorized by the incapability of lifting the feet from the floor regardless of discontinuous stepping action.
The accountable site of lesions is in the basal ganglia and frontal lobe.
- Apraxia of gait is a rare locomotion syndrome categorized by the incapability of lifting the feet from the floor regardless of discontinuous stepping action.
- The accountable site of lesions is in the basal ganglia and frontal lobe.
- Task-specific apraxia:
These include-
Sitting apraxia
Dressing apraxia
Eyelid opening apraxia
-culomotor (difficulty moving the eye)
- These include-
Sitting apraxia
Dressing apraxia
Eyelid opening apraxia
-culomotor (difficulty moving the eye)
- Sitting apraxia
- Dressing apraxia
- Eyelid opening apraxia
- oculomotor (difficulty moving the eye)
# Pathophysiology
- 'Praxis' comprises three components, which include ideation, motor planning, and execution to carry out the purposeful movement. There are particular regions of the brain that represent specific component functions, and these regions together work as a ‘praxis system’ to process and execute a purposeful movement. Dysfunction in any of these regions, namely, frontal and parietal cortex, basal ganglia, and the white matter which connects theses areas, leads to apraxia.
- The movements which requires tools are transitive movements, and the ones which do not require tools are intransitive. The intransitive movements are gestural which can be meaningful (communicative), or meaningless movements (not representational). In apraxia, transitive movements are affected more frequently as compared to intransitive movements.
- The observations of the patients in the clinical practice is the basis of most of the knowledge about 'apraxia'. Apraxia has been mostly seen in chronic left hemispheric lesions and Alzheimer's disease. The left hemispheric lesions cause more difficulty to perform transitive movements, as compared to intransitive movements and imitating gestures. Left hemisphere has a major role in 'praxis' and this may be due to specific stored representations in left hemisphere and their retrieval. On the other hand, Alzheimer's patients have preserved transitive movements, but shows deficits in gestures. Therefore, the type of apraxia depends on the type of neurological disease and the area of the brain affected by it.
- Different brain regions which have role in cognition and movement are involved in complex 'Praxis' movements. The conceptualization of a purposeful task involves prefrontal, left premotor, middle temporal and parietal areas of the brain.
- Neuroimaging studies have been done to investigate praxis correlations, but studies done so far vary widely on focus areas of praxis. One of the study reported left temporal lobe correlation with praxis because of its role in somatic memory retrieval. Left premotor cortex, left parietal lobule, and parietal cortex have also been shown to have a role in praxis as they are involved in knowledge of tools and their use, grasping movements, and spatiotemporal information integration, respectively. Stronger left lateralization (especially posterior parietal and premotor cortex) for gesture production in praxis has been suggested by neuroimaging studies.
# Causes
- The most common causes of apraxia are:
Neurodegenerative illness
Brain tumor
Dementia
Stroke
Traumatic brain injury
- Neurodegenerative illness
- Brain tumor
- Dementia
- Stroke
- Traumatic brain injury
# Epidemiology and Demographics
- The information available on the incidence of apraxia in adults is limited.
- As apraxia is most common in children, the incidence is approximately 1 to 2 children per 1,000 (0.1%–0.2%) worldwide.
- Prevalence rates of apraxia range among 0 and 34% for patients with Right hemisphere stroke and 28–57% for patients with Left hemisphere stroke.Real tool-use loss prevalence rates were stated with 25–54% impaired level of patients.
- Apraxia commonly affects individuals older than 50 years of age. Apraxia affects men and women equally
# Differentiating Apraxia from Other Diseases
# Risk Factors
- Apraxia is a rare disease caused by stroke; it has the same risk factors as a stroke.
High blood pressure
High cholesterol
Diabetes
Smoking
Prior stroke or cardiovascular disease
Prior transient ischemic attack (TIA)
Dialysis treatment
- High blood pressure
- High cholesterol
- Diabetes
- Smoking
- Prior stroke or cardiovascular disease
- Prior transient ischemic attack (TIA)
- Dialysis treatment
# Screening
- There is insufficient evidence to recommend routine screening for apraxia.
# Natural History, Complications, and Prognosis
- The symptoms of apraxia typically develop during early or later years depending on the cause and the location affected.
- Often, patients with apraxia are not aware of their shortfalls. Therefore, the history of a patient's capability to accomplish skilled movements should be obtained from the patient's caregiver or the patient himself.
- Caregivers should be asked about the capability of patients to perform activities of daily living and perform tasks involving household tools such as using a toothbrush, knife, and fork appropriately, using kitchen utensils correctly and safely to prepare a meal; using tools such as scissors or hammer correctly.
- Caregivers should also be asked about the whole activity level of the patient and whether decreases in his or her total actions have happened.
- The patient may sit on the couch and watch television without showing interest in essential activities he or she use to do in the past.
- This indifference can be related to many kinds of brain dysfunction, but it sporadically occurs because the patient is incapable of performing his or her usual activities.
- Common complications of apraxia include:
Broca's Aphasia
Acalculi
Right-left Confusion
Alexia with agraphia
Wernicke's Aphasia
- Broca's Aphasia
- Acalculi
- Right-left Confusion
- Alexia with agraphia
- Wernicke's Aphasia
- Patients with apraxia are not able to do things independently and may distress carrying out everyday responsibilities. Activities should be avoided that can lead to injury and take the appropriate safety actions. Over-all, patients with apraxia rely on others for their daily activities and need at least some notch of command; skilled nursing care may be obligatory. Patients with the tumor or degenerative diseases usually develop into amplified levels of dependence.
- The prognosis for individuals with apraxia varies. With therapy, some patients improve significantly, while others may show very little improvement. Some individuals with apraxia may benefit from the use of a communication aid.
# Diagnosis
- Many tests have been developed to evaluate apraxia but most are difficult to apply in clinics as they are not rapid tests. Additionally, most of those lack in sensitivity and validity.
De Renzi ideomotor apraxia test for ideomotor apraxia assessment, can be tested in either side brain damage. It is a 24-item scale test.
Test of upper limb apraxia (TULIA) is a 48 item test, is preferred test as it has a good validity and reliability. It can be used to test-
non-symbolic (meaningless)
intransitive (communicative)
transitive (tool-related) gestures.20
Apraxia Screen of TULIA (AST) is a short bedside test with 12 items, with a high sensitivity and specificity. The basis of this test is TULIA test.
- De Renzi ideomotor apraxia test for ideomotor apraxia assessment, can be tested in either side brain damage. It is a 24-item scale test.
- Test of upper limb apraxia (TULIA) is a 48 item test, is preferred test as it has a good validity and reliability. It can be used to test-
non-symbolic (meaningless)
intransitive (communicative)
transitive (tool-related) gestures.20
- non-symbolic (meaningless)
- intransitive (communicative)
- transitive (tool-related) gestures.20
- Apraxia Screen of TULIA (AST) is a short bedside test with 12 items, with a high sensitivity and specificity. The basis of this test is TULIA test.
- Physical examination of patients with Apraxia is usually dependent on what type of Apraxia they have for example Ideomotor apraxia, Buccofacial apraxia, and Constructional apraxia.
Ideomotor apraxia
Patients with ideomotor apraxia are tested based on the physical examination performed at the bedside with simple tests for the capability to use tools.
For example, the patients cannot hammer a nail into the (unreal) wall in front of them; patients are given a pair of scissors to cut a piece of paper.
However, different pantomimes could be made, including cutting with a saw, brushing teeth, peeling a potato or whipping eggs with an eggbeater.
Any error in carrying out the above activities indicates a loss of familiarity about the movement to be completed.
The response is recorded as an error.
Buccofacial apraxia
Patients cannot do skilled actions.
Constructional apraxia
Failure to copy or draw quality images.
Localizes lesions involving frontal or parietal area.
- Ideomotor apraxia
Patients with ideomotor apraxia are tested based on the physical examination performed at the bedside with simple tests for the capability to use tools.
For example, the patients cannot hammer a nail into the (unreal) wall in front of them; patients are given a pair of scissors to cut a piece of paper.
However, different pantomimes could be made, including cutting with a saw, brushing teeth, peeling a potato or whipping eggs with an eggbeater.
Any error in carrying out the above activities indicates a loss of familiarity about the movement to be completed.
The response is recorded as an error.
- Patients with ideomotor apraxia are tested based on the physical examination performed at the bedside with simple tests for the capability to use tools.
- For example, the patients cannot hammer a nail into the (unreal) wall in front of them; patients are given a pair of scissors to cut a piece of paper.
- However, different pantomimes could be made, including cutting with a saw, brushing teeth, peeling a potato or whipping eggs with an eggbeater.
- Any error in carrying out the above activities indicates a loss of familiarity about the movement to be completed.
- The response is recorded as an error.
- Buccofacial apraxia
Patients cannot do skilled actions.
- Patients cannot do skilled actions.
- Constructional apraxia
Failure to copy or draw quality images.
Localizes lesions involving frontal or parietal area.
- Failure to copy or draw quality images.
- Localizes lesions involving frontal or parietal area.
- There are no ECG findings associated with apraxia.
- There are no x-ray findings associated with apraxia.
- There are no echocardiography/ultrasound findings associated with apraxia.
- Brain CT scan may be helpful in the diagnosis of apraxia to evaluate for possible mass lesion or atrophy
- Brain MRI may be helpful in the diagnosis of apraxia. Findings on MRI diagnostic of apraxia include atrophy, ischemic changes, and mass lesion.
- There are no other imaging findings associated with apraxia.
- Diagnostic study PET may be helpful in the diagnosis of apraxia.
# Treatment
- Generally, treatment for individuals with apraxia includes physical therapy, occupational therapy or speech therapy. If apraxia is a symptom of another disorder (usually a neurologic disorder), the underlying disorder should be treated.
- No standardized treatment is available for apraxia. The frequency of limb apraxia in left hemispheric stroke patients is reported to be nearly 51%, and, hence, the therapeutic efforts are so far mostly concentrated towards stroke patients (left hemispheric stroke patients). Based on the studies, following treatment modalities have been considered so far-
Rehabilitative treatment- 30 sessions, each lasting 50 minutes, 3 times weekly have been tried.
Behavioral training Program-These include gesture-production exercises.
- Rehabilitative treatment- 30 sessions, each lasting 50 minutes, 3 times weekly have been tried.
- Behavioral training Program-These include gesture-production exercises.
- With treatment, an improvement in praxis and daily living activities is seen in apraxia patients, based on some studies. The communicative gestures training has led to significant improvement of the gestures which were practiced during the training sessions, with some unpracticed gestures also showing some improvement. However, the sustainability of these positive results is not clear. Although rehabilitative training has been reported to benefit, but, for sustained benefit, training alone is not sufficient.
- Noninvasive brain stimulation- This method had been used widely for many neurological disorders, but there is very limited data for its use in cognitive disorders. However, some studies have shown that this technique has been tried for therapeutic and investigational purpose for this complex neurological disorder and may show some positive results. This technique when used with rehabilitative training, may be useful. Through this technique and different stimulation settings, inhibitory or excitatory influences are exerted on cortical excitability or plasticity. The synergistic approach using this technique prior to rehabilitative training, not only increases the efficacy, but it also increases the sustainability of the improvement seen. Some examples of non-invasive brain stimulation techniques which have been used in some neurological conditions with some improvement in the cognitive function components of the disease can be tried-
Transcranial direct current stimulation (tDCS)-low-level continuous electric current is delivered to influence plasticity and excitabililty of the cortex. In this, anodal tDCS works in excitatory ways, and cathodal tDCS in inhibitory ways.
single-pulse or rTMS- It can be delivered in either low frequency (0.2–1 Hz) for inhibitory mode, or in high frequency (≥5 Hz) for excitatory mode.
theta-burst stimulation (TBS)-It is also a magnetic stimulation method like rTMS, but it shows equal efficacy even with shorter stimulation period.
paired associative stimulation (PAS)- This stimulation technique can be used to tackle physiological mechanisms underlying memory using long-term depression (LTD), and long-term potentiation (LTP).
- Transcranial direct current stimulation (tDCS)-low-level continuous electric current is delivered to influence plasticity and excitabililty of the cortex. In this, anodal tDCS works in excitatory ways, and cathodal tDCS in inhibitory ways.
- single-pulse or rTMS- It can be delivered in either low frequency (0.2–1 Hz) for inhibitory mode, or in high frequency (≥5 Hz) for excitatory mode.
- theta-burst stimulation (TBS)-It is also a magnetic stimulation method like rTMS, but it shows equal efficacy even with shorter stimulation period.
- paired associative stimulation (PAS)- This stimulation technique can be used to tackle physiological mechanisms underlying memory using long-term depression (LTD), and long-term potentiation (LTP).
- There are no specific recommended therapeutic interventions for the management of Apraxia
- Apraxia is believed to have an adverse impact on the Activity of Daily Living independence. There are limited information and research available regarding various treatments. Various interventions include:
Daily living doings training: this method explains internal and external compensatory approaches that permit a functional mission to be accomplished.
Sensory Stimulation: Including deep pressure stimulation, soft and sharp touch are useful to the patients' limbs.
Chaining (forward or backward): This method is fragmented down into its sections. The task is done with assistance from the therapist separately from the final element through backward chaining, which the patient performs out unassisted. If positive next time, additional steps are presented. Forward chaining is the opposite of backward chaining;
Proprioceptive stimulation: The patient props on and puts his weight through their upper and lower extremities;
Cueing, physical or verbal stimuli: This technique enables each phase of the task to be completed
- Daily living doings training: this method explains internal and external compensatory approaches that permit a functional mission to be accomplished.
- Sensory Stimulation: Including deep pressure stimulation, soft and sharp touch are useful to the patients' limbs.
- Chaining (forward or backward): This method is fragmented down into its sections. The task is done with assistance from the therapist separately from the final element through backward chaining, which the patient performs out unassisted. If positive next time, additional steps are presented. Forward chaining is the opposite of backward chaining;
- Proprioceptive stimulation: The patient props on and puts his weight through their upper and lower extremities;
- Cueing, physical or verbal stimuli: This technique enables each phase of the task to be completed
- Surgical intervention is not recommended for the management of Apraxia.
- There are no established measures for the primary prevention of Apraxia. Some steps can be used which include.
Exercise regularly.
Eat a healthy diet.
Limit how much alcohol you drink.
Quit smoking
Check your blood pressure often.
- Exercise regularly.
- Eat a healthy diet.
- Limit how much alcohol you drink.
- Quit smoking
- Check your blood pressure often.
Effective measures for the secondary prevention of Apraxia include secondary prevention of stroke.
- Aspirin, clopidogrel, extended-release dipyridamole, ticlopidine
- Anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban, warfarin)
- Blood pressure-lowering medications.
- Diabetes Control
- Low-fat diet
- Cholesterol-lowering medications, Cessation of cigarette smoking, carotid revascularization
- Weight loss and Exercise
# Related Chapters
- Dyspraxia | Apraxia
Template:DiseaseDisorder infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Parul Pahal, M.B.B.S[2] Norina Usman, M.B.B.S[3]
Synonyms and keywords: Dyspraxia
# Overview
Praxis, a Greek work for act, work, or deed, is the ability to perform the learned movements. It usually comprises of three components, namely, ideation (what to do), motor planning (how to do), and execution (performing the movement correctly), that results in purposeful movements. Apraxia, however, is the inability to execute these skilled and learned purposeful movements when there is a breakdown in any component of praxis. This disorder makes it difficult to perform daily tasks and negatively impact the quality of life. Apraxia, a complex neurological disorder, with cognitive-motor dysfunction may be acquired or developmental. It can occur as a result of brain trauma/disease, and higher motor functional neuronal pathways damage in the setting of preserved comprehension, coordination, motivation, and elementary sensory and motor systems. The most common types of apraxia are 'Ideational' and 'Ideomotor'.
# Historical Perspective
- Steinthal introduced the term apraxiae (Greek word meaning inaction) in 1871. However, a German physician, Hugo Lipmann first established the conceptual knowledge and published complete description of apraxia after studying the gestures in a 48-year old stroke patient who had a left hemispheric stroke.[1]
- Lipmann noticed that, despite of resolution of the paresis, the patient was unable to perform tasks such as buttoning the shirt, with no affect on spontaneous movements, and doing simple tasks on command. He observed this phenomenon specifically in patients with left hemispheric lesions. He also concluded that the planning of the motor movements occurs in the motor area of the left side of the brain. Lipmann further proposed that the 'praxis' information flows from the posterior brain areas (parietal and occipital lobes) to the anterior (motor cortex).
- The major subtypes classified by Lipmann were ideational, ideomotor, and limb-kinetic apraxia.
- One of the behavioral neurologist, Norman Geschwind, presented that the superior longitudinal fasciculus involvement disconnects the Wernicke's area are from the left premotor cortex, leading to 'apraxia'[2]
# Classification
- Ideomotor apraxia:
Most common type of apraxia.
Decreased performance of skilled motor performances despite integral language, sensory and motor function.
Seen more frequently in neurodegenerative disorders and stroke patients.
It can be classically demonstrated when a patient questioned verbally to make a motion with a limb. Patients with Ideomotor apraxia display spatial and temporal errors, inconvenient timing, amplitude, sequencing, configuration, limb position in space.
It is an inability to carry out, learned motor acts, command, adequate motor, and sensory abilities.
Ideomotor apraxia can be due to cerebral damage in numerous areas, including the left parietal lobe, the intrahemispheric association fibers, the dominant hemisphere motor association cortex, and the anterior corpus callosum.
Patients often use their arm as an object relatively than indicating how to use the object . Patients are frequently able to achieve the same acts without struggle in their daily lives. This process has been called the "voluntary-automatic dissociation".
These patients have a deficiency in their skill to plan or ample motor actions that depend on semantic memory. They can describe how to achieve a response, but incapable to "imagine" or do the movement. Though the capability to perform an act inevitably when cued remains complete, this is recognized as automatic-voluntary dissociation.In Ideomotor apraxia, there is difficulty or inability to execute familiar or learned movements on command despite of understanding the command and willingness to perform that action. The characteristic of this type of apraxia is the inability to a transitive movement. For example, the person can describe how a tool such as comb is used, but, when asked to use that tool, he is unable to perform the task (i.e. combing the hair) using the comb[4][5][6][7]
- Most common type of apraxia.
- Decreased performance of skilled motor performances despite integral language, sensory and motor function.
- Seen more frequently in neurodegenerative disorders and stroke patients.
- It can be classically demonstrated when a patient questioned verbally to make a motion with a limb. Patients with Ideomotor apraxia display spatial and temporal errors, inconvenient timing, amplitude, sequencing, configuration, limb position in space.
- It is an inability to carry out, learned motor acts, command, adequate motor, and sensory abilities.
- Ideomotor apraxia can be due to cerebral damage in numerous areas, including the left parietal lobe, the intrahemispheric association fibers, the dominant hemisphere motor association cortex, and the anterior corpus callosum.
- Patients often use their arm as an object relatively than indicating how to use the object . Patients are frequently able to achieve the same acts without struggle in their daily lives. This process has been called the "voluntary-automatic dissociation".
- These patients have a deficiency in their skill to plan or ample motor actions that depend on semantic memory. They can describe how to achieve a response, but incapable to "imagine" or do the movement. Though the capability to perform an act inevitably when cued remains complete, this is recognized as automatic-voluntary dissociation.In Ideomotor apraxia, there is difficulty or inability to execute familiar or learned movements on command despite of understanding the command and willingness to perform that action. The characteristic of this type of apraxia is the inability to a transitive movement. For example, the person can describe how a tool such as comb is used, but, when asked to use that tool, he is unable to perform the task (i.e. combing the hair) using the comb[4][5][6][7]
- Ideational apraxia:
As the name depicts, the problem is in conceptualization of the task.
The person may be able to name the objects correctly but fails to coceptualize how that object is used.
Inability to create a plan for or idea of a specific movement, for example, "pick up this pen and write down your name"
- As the name depicts, the problem is in conceptualization of the task.
- The person may be able to name the objects correctly but fails to coceptualize how that object is used.
- Inability to create a plan for or idea of a specific movement, for example, "pick up this pen and write down your name"
- Constructional apraxia:
It is a condition resulting from neurological damage, which is demonstrated by the inability to construct and copy to command two- and three-dimensional stimuli.
Constructional apraxia has been a classic sign of a parietal lobe lesion, and as a valuable tool to escalate the spatial abilities functioned by this lobe.
It has become gradually clear that Constructional apraxia is a complex construct that can be observed with very different tasks that are only slightly interrelated, and hit various kinds of visuospatial, attentional, perceptual, planning, and motor mechanisms.
The patient with constructional apraxia is unable to construct, draw, or copy simple configurations; for example, intersecting shapes; they have trouble drawing basic shapes or copying a simple diagram[8].
inability to draw or construct simple configurations
- It is a condition resulting from neurological damage, which is demonstrated by the inability to construct and copy to command two- and three-dimensional stimuli.
- Constructional apraxia has been a classic sign of a parietal lobe lesion, and as a valuable tool to escalate the spatial abilities functioned by this lobe.
- It has become gradually clear that Constructional apraxia is a complex construct that can be observed with very different tasks that are only slightly interrelated, and hit various kinds of visuospatial, attentional, perceptual, planning, and motor mechanisms.
- The patient with constructional apraxia is unable to construct, draw, or copy simple configurations; for example, intersecting shapes; they have trouble drawing basic shapes or copying a simple diagram[8].
- inability to draw or construct simple configurations
- Buccofacial or orofacial apraxia:
These patients cannot convey facial movements on requests, such as voluntary movements of the tongue, cheeks, lips, pharynx, or larynx on command, for example, include licking lips, whistling, coughing, or winking).
- These patients cannot convey facial movements on requests, such as voluntary movements of the tongue, cheeks, lips, pharynx, or larynx on command, for example, include licking lips, whistling, coughing, or winking).
- Limb-kinetic apraxia:
It is the failure to make precise movements with an arm, finger, or leg. For example, a person may have trouble tying their shoes, waving hello, or typing on a computer.
Inability to make fine, precise movements with a limb
- It is the failure to make precise movements with an arm, finger, or leg. For example, a person may have trouble tying their shoes, waving hello, or typing on a computer.
- Inability to make fine, precise movements with a limb
- Gait apraxia:
Apraxia of gait is a rare locomotion syndrome categorized by the incapability of lifting the feet from the floor regardless of discontinuous stepping action.
The accountable site of lesions is in the basal ganglia and frontal lobe[9].
- Apraxia of gait is a rare locomotion syndrome categorized by the incapability of lifting the feet from the floor regardless of discontinuous stepping action.
- The accountable site of lesions is in the basal ganglia and frontal lobe[9].
- Task-specific apraxia:
These include-
Sitting apraxia
Dressing apraxia
Eyelid opening apraxia
oculomotor (difficulty moving the eye)
- These include-
Sitting apraxia
Dressing apraxia
Eyelid opening apraxia
oculomotor (difficulty moving the eye)
- Sitting apraxia
- Dressing apraxia
- Eyelid opening apraxia
- oculomotor (difficulty moving the eye)
# Pathophysiology
- 'Praxis' comprises three components, which include ideation, motor planning, and execution to carry out the purposeful movement. There are particular regions of the brain that represent specific component functions, and these regions together work as a ‘praxis system’ to process and execute a purposeful movement. Dysfunction in any of these regions, namely, frontal and parietal cortex, basal ganglia, and the white matter which connects theses areas, leads to apraxia.
- The movements which requires tools are transitive movements, and the ones which do not require tools are intransitive. The intransitive movements are gestural which can be meaningful (communicative), or meaningless movements (not representational). In apraxia, transitive movements are affected more frequently as compared to intransitive movements.[10][11]
- The observations of the patients in the clinical practice is the basis of most of the knowledge about 'apraxia'. Apraxia has been mostly seen in chronic left hemispheric lesions and Alzheimer's disease.[12][13][14][15] The left hemispheric lesions cause more difficulty to perform transitive movements, as compared to intransitive movements and imitating gestures. Left hemisphere has a major role in 'praxis' and this may be due to specific stored representations in left hemisphere and their retrieval.[16] On the other hand, Alzheimer's patients have preserved transitive movements, but shows deficits in gestures.[15][17][18] Therefore, the type of apraxia depends on the type of neurological disease and the area of the brain affected by it.
- Different brain regions which have role in cognition and movement are involved in complex 'Praxis' movements. The conceptualization of a purposeful task involves prefrontal, left premotor, middle temporal and parietal areas of the brain.[19]
- Neuroimaging studies have been done to investigate praxis correlations, but studies done so far vary widely on focus areas of praxis. One of the study reported left temporal lobe correlation with praxis because of its role in somatic memory retrieval.[20][21][22] Left premotor cortex, left parietal lobule, and parietal cortex have also been shown to have a role in praxis as they are involved in knowledge of tools and their use,[23][24][25] grasping movements,[20][26][27][28] and spatiotemporal information integration,[27][29] respectively. Stronger left lateralization (especially posterior parietal and premotor cortex) for gesture production in praxis has been suggested by neuroimaging studies.[23][30][31]
# Causes
- The most common causes of apraxia are[32]:
Neurodegenerative illness
Brain tumor
Dementia
Stroke
Traumatic brain injury
- Neurodegenerative illness
- Brain tumor
- Dementia
- Stroke
- Traumatic brain injury
# Epidemiology and Demographics
- The information available on the incidence of apraxia in adults is limited.
- As apraxia is most common in children, the incidence is approximately 1 to 2 children per 1,000 (0.1%–0.2%) worldwide.
- Prevalence rates of apraxia range among 0 and 34% for patients with Right hemisphere stroke and 28–57% for patients with Left hemisphere stroke.Real tool-use loss prevalence rates were stated with 25–54% impaired level of patients.
- Apraxia commonly affects individuals older than 50 years of age. Apraxia affects men and women equally[33][34][35]
# Differentiating Apraxia from Other Diseases
# Risk Factors
- Apraxia is a rare disease caused by stroke; it has the same risk factors as a stroke.
High blood pressure
High cholesterol
Diabetes
Smoking
Prior stroke or cardiovascular disease
Prior transient ischemic attack (TIA)
Dialysis treatment
- High blood pressure
- High cholesterol
- Diabetes
- Smoking
- Prior stroke or cardiovascular disease
- Prior transient ischemic attack (TIA)
- Dialysis treatment
# Screening
- There is insufficient evidence to recommend routine screening for apraxia.
# Natural History, Complications, and Prognosis
- The symptoms of apraxia typically develop during early or later years depending on the cause and the location affected.
- Often, patients with apraxia are not aware of their shortfalls. Therefore, the history of a patient's capability to accomplish skilled movements should be obtained from the patient's caregiver or the patient himself.
- Caregivers should be asked about the capability of patients to perform activities of daily living and perform tasks involving household tools such as using a toothbrush, knife, and fork appropriately, using kitchen utensils correctly and safely to prepare a meal; using tools such as scissors or hammer correctly.
- Caregivers should also be asked about the whole activity level of the patient and whether decreases in his or her total actions have happened.
- The patient may sit on the couch and watch television without showing interest in essential activities he or she use to do in the past.
- This indifference can be related to many kinds of brain dysfunction, but it sporadically occurs because the patient is incapable of performing his or her usual activities[40].
- Common complications of apraxia include:
Broca's Aphasia
Acalculi
Right-left Confusion
Alexia with agraphia
Wernicke's Aphasia
- Broca's Aphasia
- Acalculi
- Right-left Confusion
- Alexia with agraphia
- Wernicke's Aphasia
- Patients with apraxia are not able to do things independently and may distress carrying out everyday responsibilities. Activities should be avoided that can lead to injury and take the appropriate safety actions. Over-all, patients with apraxia rely on others for their daily activities and need at least some notch of command; skilled nursing care may be obligatory. Patients with the tumor or degenerative diseases usually develop into amplified levels of dependence[41].
- The prognosis for individuals with apraxia varies. With therapy, some patients improve significantly, while others may show very little improvement. Some individuals with apraxia may benefit from the use of a communication aid.
# Diagnosis
- Many tests have been developed to evaluate apraxia but most are difficult to apply in clinics as they are not rapid tests. Additionally, most of those lack in sensitivity and validity.
De Renzi ideomotor apraxia test[42] for ideomotor apraxia assessment, can be tested in either side brain damage. It is a 24-item scale test.
Test of upper limb apraxia (TULIA)[43] is a 48 item test, is preferred test as it has a good validity and reliability. It can be used to test-
non-symbolic (meaningless)
intransitive (communicative)
transitive (tool-related) gestures.20
Apraxia Screen of TULIA (AST)[43] is a short bedside test with 12 items, with a high sensitivity and specificity. The basis of this test is TULIA test.
- De Renzi ideomotor apraxia test[42] for ideomotor apraxia assessment, can be tested in either side brain damage. It is a 24-item scale test.
- Test of upper limb apraxia (TULIA)[43] is a 48 item test, is preferred test as it has a good validity and reliability. It can be used to test-
non-symbolic (meaningless)
intransitive (communicative)
transitive (tool-related) gestures.20
- non-symbolic (meaningless)
- intransitive (communicative)
- transitive (tool-related) gestures.20
- Apraxia Screen of TULIA (AST)[43] is a short bedside test with 12 items, with a high sensitivity and specificity. The basis of this test is TULIA test.
- Physical examination of patients with Apraxia is usually dependent on what type of Apraxia they have for example Ideomotor apraxia, Buccofacial apraxia, and Constructional apraxia.
Ideomotor apraxia
Patients with ideomotor apraxia are tested based on the physical examination performed at the bedside with simple tests for the capability to use tools.
For example, the patients cannot hammer a nail into the (unreal) wall in front of them; patients are given a pair of scissors to cut a piece of paper.
However, different pantomimes could be made, including cutting with a saw, brushing teeth, peeling a potato or whipping eggs with an eggbeater.
Any error in carrying out the above activities indicates a loss of familiarity about the movement to be completed.
The response is recorded as an error[44].
Buccofacial apraxia
Patients cannot do skilled actions.
Constructional apraxia
Failure to copy or draw quality images.
Localizes lesions involving frontal or parietal area.
- Ideomotor apraxia
Patients with ideomotor apraxia are tested based on the physical examination performed at the bedside with simple tests for the capability to use tools.
For example, the patients cannot hammer a nail into the (unreal) wall in front of them; patients are given a pair of scissors to cut a piece of paper.
However, different pantomimes could be made, including cutting with a saw, brushing teeth, peeling a potato or whipping eggs with an eggbeater.
Any error in carrying out the above activities indicates a loss of familiarity about the movement to be completed.
The response is recorded as an error[44].
- Patients with ideomotor apraxia are tested based on the physical examination performed at the bedside with simple tests for the capability to use tools.
- For example, the patients cannot hammer a nail into the (unreal) wall in front of them; patients are given a pair of scissors to cut a piece of paper.
- However, different pantomimes could be made, including cutting with a saw, brushing teeth, peeling a potato or whipping eggs with an eggbeater.
- Any error in carrying out the above activities indicates a loss of familiarity about the movement to be completed.
- The response is recorded as an error[44].
- Buccofacial apraxia
Patients cannot do skilled actions.
- Patients cannot do skilled actions.
- Constructional apraxia
Failure to copy or draw quality images.
Localizes lesions involving frontal or parietal area.
- Failure to copy or draw quality images.
- Localizes lesions involving frontal or parietal area.
- There are no ECG findings associated with apraxia.
- There are no x-ray findings associated with apraxia.
- There are no echocardiography/ultrasound findings associated with apraxia.
- Brain CT scan may be helpful in the diagnosis of apraxia to evaluate for possible mass lesion or atrophy
- Brain MRI may be helpful in the diagnosis of apraxia. Findings on MRI diagnostic of apraxia include atrophy, ischemic changes, and mass lesion.
- There are no other imaging findings associated with apraxia.
- Diagnostic study PET may be helpful in the diagnosis of apraxia.
# Treatment
- Generally, treatment for individuals with apraxia includes physical therapy, occupational therapy or speech therapy. If apraxia is a symptom of another disorder (usually a neurologic disorder), the underlying disorder should be treated.
- No standardized treatment is available for apraxia. The frequency of limb apraxia in left hemispheric stroke patients is reported to be nearly 51%, and, hence, the therapeutic efforts are so far mostly concentrated towards stroke patients (left hemispheric stroke patients). Based on the studies, following treatment modalities have been considered so far-
Rehabilitative treatment[45][46]- 30 sessions, each lasting 50 minutes, 3 times weekly have been tried.[45]
Behavioral training Program-These include gesture-production exercises.[46]
- Rehabilitative treatment[45][46]- 30 sessions, each lasting 50 minutes, 3 times weekly have been tried.[45]
- Behavioral training Program-These include gesture-production exercises.[46]
- With treatment, an improvement in praxis and daily living activities is seen in apraxia patients, based on some studies. The communicative gestures training has led to significant improvement of the gestures which were practiced during the training sessions, with some unpracticed gestures also showing some improvement.[47] However, the sustainability of these positive results is not clear. Although rehabilitative training has been reported to benefit, but, for sustained benefit, training alone is not sufficient.
- Noninvasive brain stimulation- This method had been used widely for many neurological disorders, but there is very limited data for its use in cognitive disorders. However, some studies have shown that this technique has been tried for therapeutic and investigational purpose for this complex neurological disorder and may show some positive results. This technique when used with rehabilitative training, may be useful. Through this technique and different stimulation settings, inhibitory or excitatory influences are exerted on cortical excitability or plasticity.[48] The synergistic approach using this technique prior to rehabilitative training, not only increases the efficacy, but it also increases the sustainability of the improvement seen. Some examples of non-invasive brain stimulation techniques which have been used in some neurological conditions with some improvement in the cognitive function components of the disease can be tried-
Transcranial direct current stimulation (tDCS)[49]-low-level continuous electric current is delivered to influence plasticity and excitabililty of the cortex. In this, anodal tDCS works in excitatory ways, and cathodal tDCS in inhibitory ways.
single-pulse or rTMS[50]- It can be delivered in either low frequency (0.2–1 Hz) for inhibitory mode, or in high frequency (≥5 Hz) for excitatory mode.
theta-burst stimulation (TBS)[51]-It is also a magnetic stimulation method like rTMS, but it shows equal efficacy even with shorter stimulation period.
paired associative stimulation (PAS)[52]- This stimulation technique can be used to tackle physiological mechanisms underlying memory using long-term depression (LTD), and long-term potentiation (LTP).
- Transcranial direct current stimulation (tDCS)[49]-low-level continuous electric current is delivered to influence plasticity and excitabililty of the cortex. In this, anodal tDCS works in excitatory ways, and cathodal tDCS in inhibitory ways.
- single-pulse or rTMS[50]- It can be delivered in either low frequency (0.2–1 Hz) for inhibitory mode, or in high frequency (≥5 Hz) for excitatory mode.
- theta-burst stimulation (TBS)[51]-It is also a magnetic stimulation method like rTMS, but it shows equal efficacy even with shorter stimulation period.
- paired associative stimulation (PAS)[52]- This stimulation technique can be used to tackle physiological mechanisms underlying memory using long-term depression (LTD), and long-term potentiation (LTP).
- There are no specific recommended therapeutic interventions for the management of Apraxia[53][54][55][56]
- Apraxia is believed to have an adverse impact on the Activity of Daily Living independence. There are limited information and research available regarding various treatments</ref>. Various interventions include:
Daily living doings training: this method explains internal and external compensatory approaches that permit a functional mission to be accomplished.
Sensory Stimulation: Including deep pressure stimulation, soft and sharp touch are useful to the patients' limbs.
Chaining (forward or backward): This method is fragmented down into its sections. The task is done with assistance from the therapist separately from the final element through backward chaining, which the patient performs out unassisted. If positive next time, additional steps are presented. Forward chaining is the opposite of backward chaining;
Proprioceptive stimulation: The patient props on and puts his weight through their upper and lower extremities;
Cueing, physical or verbal stimuli: This technique enables each phase of the task to be completed
- Daily living doings training: this method explains internal and external compensatory approaches that permit a functional mission to be accomplished.
- Sensory Stimulation: Including deep pressure stimulation, soft and sharp touch are useful to the patients' limbs.
- Chaining (forward or backward): This method is fragmented down into its sections. The task is done with assistance from the therapist separately from the final element through backward chaining, which the patient performs out unassisted. If positive next time, additional steps are presented. Forward chaining is the opposite of backward chaining;
- Proprioceptive stimulation: The patient props on and puts his weight through their upper and lower extremities;
- Cueing, physical or verbal stimuli: This technique enables each phase of the task to be completed
- Surgical intervention is not recommended for the management of Apraxia.
- There are no established measures for the primary prevention of Apraxia. Some steps can be used which include[57].
Exercise regularly.
Eat a healthy diet.
Limit how much alcohol you drink.
Quit smoking
Check your blood pressure often.
- Exercise regularly.
- Eat a healthy diet.
- Limit how much alcohol you drink.
- Quit smoking
- Check your blood pressure often.
Effective measures for the secondary prevention of Apraxia include secondary prevention of stroke[58].
- Aspirin, clopidogrel, extended-release dipyridamole, ticlopidine
- Anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban, warfarin)
- Blood pressure-lowering medications.
- Diabetes Control
- Low-fat diet
- Cholesterol-lowering medications, Cessation of cigarette smoking, carotid revascularization
- Weight loss and Exercise
# Related Chapters
- Dyspraxia | https://www.wikidoc.org/index.php/Apraxia | |
eeb4dbfcd7a0b58cfc9f8fb55027d178ad7c29ea | wikidoc | Apricot | Apricot
The Apricot (Prunus armeniaca, "Armenian plum" in Latin, syn. Armeniaca vulgaris Lam., Armenian: Ծիրան, Chinese: 杏 xing, Urdu: ﺧﯘﺑﺎﻧﯽ khúbánī) is a species of Prunus, classified with the plum in the subgenus Prunus. The native range is somewhat uncertain due to its extensive prehistoric cultivation, but most likely in northern and western China and Central Asia, possibly also Korea and Japan.
# Description
It is a small tree 8–12 m tall, with a trunk up to 40 cm diameter and a dense, spreading canopy. The leaves are ovate, 5–9 cm long and 4–8 cm wide, with a rounded base, a pointed tip and a finely serrated margin. The flowers are 2–4.5 cm diameter, with five white to pinkish petals; they are produced singly or in pairs in early spring before the leaves. The fruit is a drupe similar to a small peach, 1.5–2.5 cm diameter (larger in some modern cultivars), from yellow to orange, often tinged red on the side most exposed to the sun; its surface is usually pubescent. The single seed is enclosed in a hard stony shell, often called a "stone", smooth except for three ridges running down one side.
# Cultivation and uses
## History of cultivation
The Apricot was first cultivated in China in about 3000 BC. In Armenia it was known from ancient times, having been brought along the Silk Road; it has been cultivated there so long it is often thought to be native there. Its introduction to Greece is attributed to Alexander the Great, and the Roman General Lucullus (106-57 B.C.E.) also exported some trees, cherry, white heart cherry and apricot from Armenia to Europe. Subsequent sources were often much confused over the origin of the species. Loudon (1838) believed it had a wide native range including Armenia, Caucasus, the Himalaya, China and Japan. Nearly all sources presume that because it is named armeniaca, the tree must be native to or have originated in Armenia as the Romans knew it. For example, De Poerderlé asserts: "Cet arbre tire son name de l'Arménie, province d'Asie, d'où il est originaire et d'où il fut porté en Europe ...." ("this tree takes its name from Armenia, province of Asia, where it is native, and whence it was brought to Europe ....") There is no scientific evidence to support such a view. Today the cultivars have spread to all parts of the globe with climates that support it.
Apricots have been cultivated in Persia since antiquity, and dried ones were an important commodity on Persian trade routes. Apricots remain an important fruit in modern-day Iran where they are known under the common name of Zard-ālū (Persian زردالو).
Apricots are also cultivated in Egypt and are among the common fruits well known there. The season in which apricot is present in the market in Egypt is very short. There is even an Egyptian proverb that says "Fel meshmesh" (English "in the apricot") which is used to refer to something that will not happen because the apricot disappears from the market in Egypt so shortly after it has appeared. Egyptians usually dry apricot and sweeten it then use it to make a drink called "amar el deen".
More recently, English settlers brought the apricot to the English colonies in the New World. Most of modern American production of apricots comes from the seedlings carried to the west coast by Spanish missionaries. Almost all U.S. production is in California, with some in Washington and Utah..
Many apricots are also cultivated in Australia, particularly South Australia where they are commonly grown in the region known as the Riverland and in a small town called Mypolonga in the Lower Murray region of the state. In states other than South Australia apricots are still grown, particularly in Tasmania and western Victoria and southwest New South Wales, but they are less common than in South Australia.
## Cultivation
Although often thought of as a "subtropical" fruit, the Apricot is native to a continental climate region with cold winters. The tree is slightly more cold-hardy than the peach, tolerating winter temperatures as cold as −30 °C or lower if healthy. The limiting factor in apricot culture is spring frosts: They tend to flower very early, around the time of the vernal equinox even in northern locations like the Great Lakes region, meaning spring frost often kills the flowers. The trees do need some winter cold (even if minimal) to bear and grow properly and do well in Mediterranean climate locations since spring frosts are less severe but there is some cool winter weather to allow a proper dormancy. The dry climate of these areas is best for good fruit production. Hybridisation with the closely related Prunus sibirica (Siberian Apricot; hardy to −50°C but with less palatable fruit) offers options for breeding more cold-tolerant plants.
Apricot cultivars are most often grafted on plum or peach rootstocks. A cutting of an existing apricot plant provides the fruit characteristics such as flavour, size, etc., but the rootstock provides the growth characteristics of the plant. Apricots and plums can hybridize with each other and produce fruit that are variously called pluots, plumcots, or apriums. Apricots are grown commercially in the United States, primarily in California and Washington.
Apricots have a chilling requirement of 300 to 900 chilling units. They are hardy in USDA zones 5 through 8. Some of the more popular cultivars of apricots include 'Blenheim', 'Wenatchee Moorpark', 'Tilton', and 'Perfection'.
There is an old adage that an apricot tree will not grow far from the mother tree. The implication is that apricots are particular about the soil conditions in which they are grown. They prefer a well-drained soil with a pH of 6.0 to 7.0. If fertilizer is needed, as indicated by yellow-green leaves, then 1/4 pound of 10-10-10 fertilizer should be applied in the second year. Granular fertilizer should be scattered beneath the branches of the tree. An additional 1/4 pound should be applied for every year of age of the tree in early spring, before growth starts. Apricots are self-compatible and do not require pollinizer trees, with the exception of the 'Moongold' and 'Sungold' cultivars, which can pollinate each other. Apricots are susceptible to numerous bacterial diseases including bacterial canker and blast, bacterial spot and crown gall. They are susceptible to an even longer list of fungal diseases including brown rot, Alternaria spot and fruit rot, and powdery mildew. Other problems for apricots are nematodes and viral diseases, including graft-transmissible problems.
## Production trends
Turkey is the leading apricot producer, followed by Iran. In Armenia apricots are grown in Ararat Valley.
## Kernels
Seeds or kernels of the apricot grown in central Asia and around the Mediterranean are so sweet that they may be substituted for almonds. The Italian liqueur Amaretto and amaretti biscotti are flavoured with extract of apricot kernels rather than almonds. Oil pressed from these cultivars has been used as cooking oil.
## Medicinal and non-food uses
Cyanogenic glycosides (found in most stone fruit seeds, bark, and leaves) are found in high concentration in apricot seeds. Laetrile, a purported alternative treatment for cancer, is extracted from apricot seeds. As early as the year 502, apricot seeds were used to treat tumors, and in the 17th century apricot oil was used in England against tumors and ulcers. However, in 1980 the National Cancer Institute in the USA claimed laetrile to be an ineffective cancer treatment.
In Europe, apricots were long considered an aphrodisiac, and were used in this context in William Shakespeare's A Midsummer Night's Dream, and as an inducer of childbirth, as depicted in John Webster's The Duchess of Malfi.
Due to their high fiber to volume ratio, dried apricots are sometimes used to relieve constipation or induce diarrhea. Effects can be felt after eating as little as three.
# Etymology
The scientific name armeniaca was first used by Gaspard Bauhin in his Pinax Theatri Botanici (page 442), referring to the species as mala armeniaca "Armenian apple". Most believed and many still believe that it came from Pliny the Elder; however, it is not used by Pliny or any other classical author, even in Late Latin. Linnaeus took up Bauhin's epithet in the first edition of his Species Plantarum in 1753.
The epithet probably is derived from an etymological identification of a tree mentioned in Pliny with the apricot. Pliny says "We give the name of apples (mala) ... to peaches (persica) and pomegranites (granata) ...." Later in the same section he states "The Asiatic peach ripens at the end of autumn, though an early variety (praecocia) ripens in summer - these were discovered within the last thirty years ...."
From this praecocia comes the standard etymology of "apricot". The classical authors connected armeniaca with praecocia: Pedanius Dioscorides' "... Template:Polytonic" and Martial's "Armeniaca, et praecocia latine dicuntur". Putting together the Armeniaca and the mala obtains the well-known epithet, but there is no evidence the ancients did it; Armeniaca alone meant the apricot.
Accordingly the American Heritage Dictionary under apricot derives praecocia from praecoquus, "cooked or ripened beforehand", becoming Greek πραικόκιον "apricot" and Arabic al-barqūq "the plum". The English name comes from earlier "abrecock" in turn from the Middle French abricot, from Catalan abercoc. Both the latter and Spanish albaricoque were adaptations of the Arabic, dating from the Moorish occupation of Spain. However, in Argentina and Chile the word for "apricot" is damasco, which probably indicates that to the Spanish settlers of Argentina the fruit was associated with Damascus in Syria.
The anecdotal evidence is the only link between the apricot and Pliny's tree, but even if true, the origin of the word is not the origin of the tree. The Romans had no idea why the tree was called armeniaca and presumed as did later botanists that it was "from Armenia", whatever that should mean. Scientifically nothing at all about the evolution or production of the wild tree or any of its cultivars or about the native range at the time of the Romans or any other time in history is implied. At best the tradition reflects Roman literary opinion concerning some now obscure horticultural events.
# In culture
The Chinese associate the apricot with education and medicine. Chuang Tzu, a Chinese philosopher in 4th century BCE, had told a story that Confucius taught his students in a forum among the wood of apricot.
In The Wizard of Oz, the Cowardly Lion sings, "What puts the ape in the apricot? Courage!"
Apricots were used by the Australian Aborigines as an aphrodisiac. A special tea was prepared from the apricot stone, while the fruit was crushed and smeared over the erogenous regions.
Among tank-driving soldiers, apricots are taboo, by superstition. Tankers will not eat apricots, allow apricots onto their vehicles, and often will not even say the word "apricot". This superstition stems from Sherman tank breakdowns purportedly happening in the presence of cans of apricots.
Dreaming of apricots, in English folklore, is said to be good luck.
The Turkish idiom "bundan iyisi Şam'da kayısı" (literally, the only thing better than this is an apricot in Damascus) means "it doesn't get any better than this" and used when something is the very best it can be; like a delicious apricot from Damascus.
The Church of Jesus Christ of Latter-Day Saints includes in their Children's Songbook the song "Popcorn Popping on the Apricot Tree" describing an apricot tree in bloom. | Apricot
The Apricot (Prunus armeniaca, "Armenian plum" in Latin, syn. Armeniaca vulgaris Lam., Armenian: Ծիրան, Chinese: 杏 xing, Urdu: ﺧﯘﺑﺎﻧﯽ khúbánī) is a species of Prunus, classified with the plum in the subgenus Prunus. The native range is somewhat uncertain due to its extensive prehistoric cultivation, but most likely in northern and western China and Central Asia, possibly also Korea and Japan.[1][2]
# Description
It is a small tree 8–12 m tall, with a trunk up to 40 cm diameter and a dense, spreading canopy. The leaves are ovate, 5–9 cm long and 4–8 cm wide, with a rounded base, a pointed tip and a finely serrated margin. The flowers are 2–4.5 cm diameter, with five white to pinkish petals; they are produced singly or in pairs in early spring before the leaves. The fruit is a drupe similar to a small peach, 1.5–2.5 cm diameter (larger in some modern cultivars), from yellow to orange, often tinged red on the side most exposed to the sun; its surface is usually pubescent. The single seed is enclosed in a hard stony shell, often called a "stone", smooth except for three ridges running down one side.[1][3]
# Cultivation and uses
## History of cultivation
Template:Nutritionalvalue
Template:Nutritionalvalue
The Apricot was first cultivated in China in about 3000 BC.[4] In Armenia it was known from ancient times, having been brought along the Silk Road;[4] it has been cultivated there so long it is often thought to be native there.[5][6] Its introduction to Greece is attributed to Alexander the Great,[4] and the Roman General Lucullus (106-57 B.C.E.) also exported some trees, cherry, white heart cherry and apricot from Armenia to Europe. Subsequent sources were often much confused over the origin of the species. Loudon (1838) believed it had a wide native range including Armenia, Caucasus, the Himalaya, China and Japan.[7] Nearly all sources presume that because it is named armeniaca, the tree must be native to or have originated in Armenia as the Romans knew it. For example, De Poerderlé asserts: "Cet arbre tire son name de l'Arménie, province d'Asie, d'où il est originaire et d'où il fut porté en Europe ...." ("this tree takes its name from Armenia, province of Asia, where it is native, and whence it was brought to Europe ....")[8] There is no scientific evidence to support such a view. Today the cultivars have spread to all parts of the globe with climates that support it.
Apricots have been cultivated in Persia since antiquity, and dried ones were an important commodity on Persian trade routes. Apricots remain an important fruit in modern-day Iran where they are known under the common name of Zard-ālū (Persian زردالو).
Apricots are also cultivated in Egypt and are among the common fruits well known there. The season in which apricot is present in the market in Egypt is very short. There is even an Egyptian proverb that says "Fel meshmesh" (English "in the apricot") which is used to refer to something that will not happen because the apricot disappears from the market in Egypt so shortly after it has appeared. Egyptians usually dry apricot and sweeten it then use it to make a drink called "amar el deen".
More recently, English settlers brought the apricot to the English colonies in the New World. Most of modern American production of apricots comes from the seedlings carried to the west coast by Spanish missionaries. Almost all U.S. production is in California, with some in Washington and Utah.[9].
Many apricots are also cultivated in Australia, particularly South Australia where they are commonly grown in the region known as the Riverland and in a small town called Mypolonga in the Lower Murray region of the state. In states other than South Australia apricots are still grown, particularly in Tasmania and western Victoria and southwest New South Wales, but they are less common than in South Australia.
## Cultivation
Although often thought of as a "subtropical" fruit, the Apricot is native to a continental climate region with cold winters. The tree is slightly more cold-hardy than the peach, tolerating winter temperatures as cold as −30 °C or lower if healthy. The limiting factor in apricot culture is spring frosts: They tend to flower very early, around the time of the vernal equinox even in northern locations like the Great Lakes region, meaning spring frost often kills the flowers. The trees do need some winter cold (even if minimal) to bear and grow properly and do well in Mediterranean climate locations since spring frosts are less severe but there is some cool winter weather to allow a proper dormancy. The dry climate of these areas is best for good fruit production. Hybridisation with the closely related Prunus sibirica (Siberian Apricot; hardy to −50°C but with less palatable fruit) offers options for breeding more cold-tolerant plants.[10]
Apricot cultivars are most often grafted on plum or peach rootstocks. A cutting of an existing apricot plant provides the fruit characteristics such as flavour, size, etc., but the rootstock provides the growth characteristics of the plant. Apricots and plums can hybridize with each other and produce fruit that are variously called pluots, plumcots, or apriums. Apricots are grown commercially in the United States, primarily in California and Washington.
Apricots have a chilling requirement of 300 to 900 chilling units. They are hardy in USDA zones 5 through 8. Some of the more popular cultivars of apricots include 'Blenheim', 'Wenatchee Moorpark', 'Tilton', and 'Perfection'.
There is an old adage that an apricot tree will not grow far from the mother tree. The implication is that apricots are particular about the soil conditions in which they are grown. They prefer a well-drained soil with a pH of 6.0 to 7.0. If fertilizer is needed, as indicated by yellow-green leaves, then 1/4 pound of 10-10-10 fertilizer should be applied in the second year. Granular fertilizer should be scattered beneath the branches of the tree. An additional 1/4 pound should be applied for every year of age of the tree in early spring, before growth starts. Apricots are self-compatible and do not require pollinizer trees, with the exception of the 'Moongold' and 'Sungold' cultivars, which can pollinate each other. Apricots are susceptible to numerous bacterial diseases including bacterial canker and blast, bacterial spot and crown gall. They are susceptible to an even longer list of fungal diseases including brown rot, Alternaria spot and fruit rot, and powdery mildew. Other problems for apricots are nematodes and viral diseases, including graft-transmissible problems.
## Production trends
Turkey is the leading apricot producer,[12] followed by Iran. In Armenia apricots are grown in Ararat Valley.
## Kernels
Seeds or kernels of the apricot grown in central Asia and around the Mediterranean are so sweet that they may be substituted for almonds. The Italian liqueur Amaretto and amaretti biscotti are flavoured with extract of apricot kernels rather than almonds. Oil pressed from these cultivars has been used as cooking oil.
## Medicinal and non-food uses
Cyanogenic glycosides (found in most stone fruit seeds, bark, and leaves) are found in high concentration in apricot seeds. Laetrile, a purported alternative treatment for cancer, is extracted from apricot seeds. As early as the year 502, apricot seeds were used to treat tumors, and in the 17th century apricot oil was used in England against tumors and ulcers. However, in 1980 the National Cancer Institute in the USA claimed laetrile to be an ineffective cancer treatment.[13]
In Europe, apricots were long considered an aphrodisiac, and were used in this context in William Shakespeare's A Midsummer Night's Dream, and as an inducer of childbirth, as depicted in John Webster's The Duchess of Malfi.
Due to their high fiber to volume ratio, dried apricots are sometimes used to relieve constipation or induce diarrhea. Effects can be felt after eating as little as three.
# Etymology
The scientific name armeniaca was first used by Gaspard Bauhin in his Pinax Theatri Botanici (page 442), referring to the species as mala armeniaca "Armenian apple". Most believed and many still believe that it came from Pliny the Elder; however, it is not used by Pliny or any other classical author, even in Late Latin. Linnaeus took up Bauhin's epithet in the first edition of his Species Plantarum in 1753.[14]
The epithet probably is derived from an etymological identification of a tree mentioned in Pliny with the apricot. Pliny says "We give the name of apples (mala) ... to peaches (persica) and pomegranites (granata) ...."[15] Later in the same section he states "The Asiatic peach ripens at the end of autumn, though an early variety (praecocia) ripens in summer - these were discovered within the last thirty years ...."
From this praecocia comes the standard etymology of "apricot". The classical authors connected armeniaca with praecocia:[16] Pedanius Dioscorides' "... Template:Polytonic"[17] and Martial's "Armeniaca, et praecocia latine dicuntur".[18] Putting together the Armeniaca and the mala obtains the well-known epithet, but there is no evidence the ancients did it; Armeniaca alone meant the apricot.
Accordingly the American Heritage Dictionary under apricot derives praecocia from praecoquus, "cooked or ripened beforehand", becoming Greek πραικόκιον "apricot" and Arabic al-barqūq "the plum". The English name comes from earlier "abrecock" in turn from the Middle French abricot, from Catalan abercoc.[19] Both the latter and Spanish albaricoque were adaptations of the Arabic, dating from the Moorish occupation of Spain. However, in Argentina and Chile the word for "apricot" is damasco, which probably indicates that to the Spanish settlers of Argentina the fruit was associated with Damascus in Syria.[20]
The anecdotal evidence is the only link between the apricot and Pliny's tree, but even if true, the origin of the word is not the origin of the tree. The Romans had no idea why the tree was called armeniaca and presumed as did later botanists that it was "from Armenia", whatever that should mean. Scientifically nothing at all about the evolution or production of the wild tree or any of its cultivars or about the native range at the time of the Romans or any other time in history is implied. At best the tradition reflects Roman literary opinion concerning some now obscure horticultural events.
# In culture
The Chinese associate the apricot with education and medicine. Chuang Tzu, a Chinese philosopher in 4th century BCE, had told a story that Confucius taught his students in a forum among the wood of apricot.[citation needed]
In The Wizard of Oz, the Cowardly Lion sings, "What puts the ape in the apricot? Courage!"
Apricots were used by the Australian Aborigines as an aphrodisiac. A special tea was prepared from the apricot stone, while the fruit was crushed and smeared over the erogenous regions.
Among tank-driving soldiers, apricots are taboo, by superstition. Tankers will not eat apricots, allow apricots onto their vehicles, and often will not even say the word "apricot". This superstition stems from Sherman tank breakdowns purportedly happening in the presence of cans of apricots.[21]
Dreaming of apricots, in English folklore, is said to be good luck.[citation needed]
The Turkish idiom "bundan iyisi Şam'da kayısı" (literally, the only thing better than this is an apricot in Damascus) means "it doesn't get any better than this" and used when something is the very best it can be; like a delicious apricot from Damascus.
The Church of Jesus Christ of Latter-Day Saints includes in their Children's Songbook the song "Popcorn Popping on the Apricot Tree" describing an apricot tree in bloom. | https://www.wikidoc.org/index.php/Apricot | |
bf0a65fcbe8722a432cbcac2953381aef4735a03 | wikidoc | Aptamer | Aptamer
Aptamers are oligonucleic acid or peptide molecules that bind a specific target molecule. Aptamers are usually created by selecting them from a large random sequence pool, but natural aptamers also exist in riboswitches. Aptamers can be used for both basic research and clinical purposes as macromolecular drugs. Aptamers can be combined with ribozymes to self-cleave in the presence of their target molecule. These compound molecules have additional research, industrial and clinical applications.
More specifically, aptamers can be classified as:
- DNA or RNA aptamers. They consist of (usually short) strands of oligonucleotides.
- Peptide aptamers. They consist of a short variable peptide domain, attached at both ends to a protein scaffold.
# RNA and DNA aptamers
Aptamers are nucleic acid species that have been engineered through repeated rounds of in vitro selection or equivalently, SELEX (systematic evolution of ligands by exponential enrichment) to bind to various molecular targets such as small molecules, proteins, nucleic acids, and even cells, tissues and organisms. Aptamers offer the utility for biotechnological and therapeutic applications as they offer molecular recognition properties that rival that of the commonly used biomolecule, antibodies. In addition to their discriminate recognition, aptamers offer advantages over antibodies as they can be engineered completely in a test tube, are readily produced by chemical synthesis, possess desirable storage properties, and elicit little or no immunogenicity in therapeutic applications.
In 1990, two labs independently developed the technique of selection: the Gold lab, utilizing the term SELEX for their process of selecting RNA ligands against T4 DNA polymerase; and the Szostak lab, coining the term in vitro selection, selecting RNA ligands against various organic dyes. The Szostak lab also coined the term aptamer (from the Latin, aptus, meaning ‘to fit’) for these nucleic acid-based ligands. Two years later, the Szostak lab and Gilead Sciences, independent of one another, utilized in vitro selection schemes to evolve single stranded DNA ligands for organic dyes and human coagulant, thrombin, respectively. There does not appear to be any systematic differences between RNA and DNA aptamers, save the greater intrinsic chemical stability of DNA.
Interestingly enough, the notion of selection in vitro was actually preceded twenty-plus years prior when the infamous Sol Spiegelman utilized a Qbeta replication system as a way to evolve a self-replicating molecule. In addition, a year before the publishing of in vitro selection and SELEX, Gerald Joyce utilized a system that he termed ‘directed evolution’ to alter the cleavage activity of a ribozyme.
Over the course of the next sixteen years, many researchers have utilized aptamer selection as a means for application and discovery. In 2001, the process of in vitro selection was automated by the Ellington lab at the University of Texas at Austin, and at SomaLogic, Inc (Boulder, CO), reducing the duration of a selection experiment from six weeks to three days.
While the process of artificial engineering of nucleic acid ligands is highly interesting to biology and biotechnology, the notion of aptamers in the natural world had yet to be uncovered until 2002 when Ronald Breaker and his coworkers discovered a nucleic acid-based genetic regulatory element called a riboswitch that possesses similar molecular recognition properties to the artificially made aptamers. In addition to the discovery of a new mode of genetic regulation, this adds further credence to the notion of an ‘RNA World,’ a postulated stage in time in the origins of life on Earth.
Lately, a concept of smart aptamers, and smart ligands in general, has been introduced. It describes aptamers that are selected with pre-defined equilibrium (K_{d}), kinetic (k_{off} , k_{on}) and thermodynamic (ΔH, ΔS) parameters of aptamer-target interaction.
Recent developments in aptamer-based therapeutics have been rewarded in the form of the first aptamer-based drug approved by the U.S. Food and Drug Administration (FDA) in treatment for age-related macular degeneration (AMD), called Macugen offered by OSI Pharmaceuticals. In addition, Cambridge, MA - based Archemix () is leading the development of aptamers as a new class of directed therapeutics for the prevention and treatment of chronic and acute diseases. ARC1779, its lead proprietary candidate, is a potent, selective, first-in-class antagonist of von Willebrand Factor (vWF). ARC1779 is being evaluated in patients diagnosed with acute coronary syndrome (ACS) who are undergoing percutaneous coronary intervention (PCI). Phase I testing for ARC1779 was initiated in December 2006, and a Phase 2 study in ACS is planned to begin by the end of 2007.
Non-modified aptamers are cleared rapidly from the bloodstream, with a half-life of minutes to hours, mainly due to nuclease degradation and clearance from the body by the kidneys, a result of the aptamer's inherently low molecular weight. Unmodified aptamer applications currently focus on treating transient conditions such as blood clotting, or treating organs such as the eye where local delivery is possible. This rapid clearance can be an advantage in applications such as in vivo diagnostic imaging. An example is a tenascin-binding aptamer under development by Schering AG for cancer imaging. Several modifications, such as 2'-fluorine-substituted pyrimidines, polyethylene glycol (PEG) linkage, etc. (both of which are used in Macugen, an FDA-approved aptamer) are available to scientists with which to increase the half-life of aptamers easily to the day or even week time scale.
In addition to the development of aptamer-based therapeutics, many researchers such as the Ellington lab and the Boulder, CO-based SomaLogic have been developing diagnostic techniques for whole cell protein profiling called proteomics, and medical diagnostics for the distinction of disease versus healthy states.
As a resource for all in vitro selection and SELEX experiments, the Ellington lab has developed the Aptamer Database cataloging all published experiments. This is found at /.
# Peptide aptamers
Peptide aptamers are proteins that are designed to interfere with other protein interactions inside cells. They consist of a variable peptide loop attached at both ends to a protein scaffold. This double structural constraint greatly increases the binding affinity of the peptide aptamer to levels comparable to an antibody's (nanomolar range).
The variable loop length is typically comprised of 10 to 20 amino acids, and the scaffold may be any protein which have good solubility and compacity properties. Currently, the bacterial protein Thioredoxin-A is the most used scaffold protein, the variable loop being inserted within the reducing active site, which is a -Cys-Gly-Pro-Cys- loop in the wild protein, the two Cysteines lateral chains being able to form a disulfide bridge.
Peptide aptamer selection can be made using different systems, but the most used is currently the yeast two-hybrid system.
Selection of Ligand Regulated Peptide Aptamers (LiRPAs) has been demonstrated. By displaying 7 amino acid peptides from a novel scaffold protein based on the trimeric FKBP-rapamycin-FRB structure, interaction between the randomized peptide and target molecule can be controlled by the small molecule Rapamycin or non-immunosuppressive analogs.
# Use as Pharmacologic Agents
It should be noted that aptamers are electrostatically highly charged and can activate the complement resulting in anaphylactoid or anaphylactic reactions. The risk of allergic reactions may be minimized by slowing the infusion rate. | Aptamer
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Aptamers are oligonucleic acid or peptide molecules that bind a specific target molecule. Aptamers are usually created by selecting them from a large random sequence pool, but natural aptamers also exist in riboswitches. Aptamers can be used for both basic research and clinical purposes as macromolecular drugs. Aptamers can be combined with ribozymes to self-cleave in the presence of their target molecule. These compound molecules have additional research, industrial and clinical applications.
More specifically, aptamers can be classified as:
- DNA or RNA aptamers. They consist of (usually short) strands of oligonucleotides.
- Peptide aptamers. They consist of a short variable peptide domain, attached at both ends to a protein scaffold.
# RNA and DNA aptamers
Aptamers are nucleic acid species that have been engineered through repeated rounds of in vitro selection or equivalently, SELEX (systematic evolution of ligands by exponential enrichment) to bind to various molecular targets such as small molecules, proteins, nucleic acids, and even cells, tissues and organisms. Aptamers offer the utility for biotechnological and therapeutic applications as they offer molecular recognition properties that rival that of the commonly used biomolecule, antibodies. In addition to their discriminate recognition, aptamers offer advantages over antibodies as they can be engineered completely in a test tube, are readily produced by chemical synthesis, possess desirable storage properties, and elicit little or no immunogenicity in therapeutic applications.
In 1990, two labs independently developed the technique of selection: the Gold lab, utilizing the term SELEX for their process of selecting RNA ligands against T4 DNA polymerase; and the Szostak lab, coining the term in vitro selection, selecting RNA ligands against various organic dyes. The Szostak lab also coined the term aptamer (from the Latin, aptus, meaning ‘to fit’) for these nucleic acid-based ligands. Two years later, the Szostak lab and Gilead Sciences, independent of one another, utilized in vitro selection schemes to evolve single stranded DNA ligands for organic dyes and human coagulant, thrombin, respectively. There does not appear to be any systematic differences between RNA and DNA aptamers, save the greater intrinsic chemical stability of DNA.
Interestingly enough, the notion of selection in vitro was actually preceded twenty-plus years prior when the infamous Sol Spiegelman utilized a Qbeta replication system as a way to evolve a self-replicating molecule. In addition, a year before the publishing of in vitro selection and SELEX, Gerald Joyce utilized a system that he termed ‘directed evolution’ to alter the cleavage activity of a ribozyme.
Over the course of the next sixteen years, many researchers have utilized aptamer selection as a means for application and discovery. In 2001, the process of in vitro selection was automated by the Ellington lab at the University of Texas at Austin, and at SomaLogic, Inc (Boulder, CO), reducing the duration of a selection experiment from six weeks to three days.
While the process of artificial engineering of nucleic acid ligands is highly interesting to biology and biotechnology, the notion of aptamers in the natural world had yet to be uncovered until 2002 when Ronald Breaker and his coworkers discovered a nucleic acid-based genetic regulatory element called a riboswitch that possesses similar molecular recognition properties to the artificially made aptamers. In addition to the discovery of a new mode of genetic regulation, this adds further credence to the notion of an ‘RNA World,’ a postulated stage in time in the origins of life on Earth.
Lately, a concept of smart aptamers, and smart ligands in general, has been introduced. It describes aptamers that are selected with pre-defined equilibrium (<math>K_{d}</math>), kinetic (<math>k_{off}</math> , <math>k_{on}</math>) and thermodynamic (ΔH, ΔS) parameters of aptamer-target interaction.
Recent developments in aptamer-based therapeutics have been rewarded in the form of the first aptamer-based drug approved by the U.S. Food and Drug Administration (FDA) in treatment for age-related macular degeneration (AMD), called Macugen offered by OSI Pharmaceuticals. In addition, Cambridge, MA - based Archemix (http://www.archemix.com) is leading the development of aptamers as a new class of directed therapeutics for the prevention and treatment of chronic and acute diseases. ARC1779, its lead proprietary candidate, is a potent, selective, first-in-class antagonist of von Willebrand Factor (vWF). ARC1779 is being evaluated in patients diagnosed with acute coronary syndrome (ACS) who are undergoing percutaneous coronary intervention (PCI). Phase I testing for ARC1779 was initiated in December 2006, and a Phase 2 study in ACS is planned to begin by the end of 2007.
Non-modified aptamers are cleared rapidly from the bloodstream, with a half-life of minutes to hours, mainly due to nuclease degradation and clearance from the body by the kidneys, a result of the aptamer's inherently low molecular weight. Unmodified aptamer applications currently focus on treating transient conditions such as blood clotting, or treating organs such as the eye where local delivery is possible. This rapid clearance can be an advantage in applications such as in vivo diagnostic imaging. An example is a tenascin-binding aptamer under development by Schering AG for cancer imaging. Several modifications, such as 2'-fluorine-substituted pyrimidines, polyethylene glycol (PEG) linkage, etc. (both of which are used in Macugen, an FDA-approved aptamer) are available to scientists with which to increase the half-life of aptamers easily to the day or even week time scale.
In addition to the development of aptamer-based therapeutics, many researchers such as the Ellington lab and the Boulder, CO-based SomaLogic have been developing diagnostic techniques for whole cell protein profiling called proteomics, and medical diagnostics for the distinction of disease versus healthy states.
As a resource for all in vitro selection and SELEX experiments, the Ellington lab has developed the Aptamer Database cataloging all published experiments. This is found at http://aptamer.icmb.utexas.edu/.
# Peptide aptamers
Peptide aptamers are proteins that are designed to interfere with other protein interactions inside cells. They consist of a variable peptide loop attached at both ends to a protein scaffold. This double structural constraint greatly increases the binding affinity of the peptide aptamer to levels comparable to an antibody's (nanomolar range).
The variable loop length is typically comprised of 10 to 20 amino acids, and the scaffold may be any protein which have good solubility and compacity properties. Currently, the bacterial protein Thioredoxin-A is the most used scaffold protein, the variable loop being inserted within the reducing active site, which is a -Cys-Gly-Pro-Cys- loop in the wild protein, the two Cysteines lateral chains being able to form a disulfide bridge.
Peptide aptamer selection can be made using different systems, but the most used is currently the yeast two-hybrid system.
Selection of Ligand Regulated Peptide Aptamers (LiRPAs) has been demonstrated. By displaying 7 amino acid peptides from a novel scaffold protein based on the trimeric FKBP-rapamycin-FRB structure, interaction between the randomized peptide and target molecule can be controlled by the small molecule Rapamycin or non-immunosuppressive analogs.
# Use as Pharmacologic Agents
It should be noted that aptamers are electrostatically highly charged and can activate the complement resulting in anaphylactoid or anaphylactic reactions. The risk of allergic reactions may be minimized by slowing the infusion rate. | https://www.wikidoc.org/index.php/Aptamer | |
31a63ef8ca54f0a9e0aaa66886b42267fee3ef68 | wikidoc | Estrone | Estrone
Estrone (also oestrone) is an estrogenic hormone secreted by the ovary.
Estrone is one of the three estrogens, which also include estriol and estradiol. Estrone is the least prevalent of the three hormones, estradiol being prevalent almost always in a female body, estriol being prevalent primarily during pregnancy. Estrone is relevant to health and disease due to its conversion to estrone sulfate, a long-lived derivative of estrone. Estrone sulfate acts as a pool of estrone which can be converted as needed to the more active estradiol.
# Synthesis
Estrone is synthesized via aromatase from androstenedione, a derivative of progesterone. The conversion consists of the de-methylation of C-19 and the aromaticity of the 'A' ring. This reaction is similar to the conversion of testosterone to estradiol.
# Additional images
- Androstenedione converting to estrone.
- Steroidogenesis | Estrone
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Estrone (also oestrone) is an estrogenic hormone secreted by the ovary.
Estrone is one of the three estrogens, which also include estriol and estradiol. Estrone is the least prevalent of the three hormones, estradiol being prevalent almost always in a female body, estriol being prevalent primarily during pregnancy. Estrone is relevant to health and disease due to its conversion to estrone sulfate, a long-lived derivative of estrone. Estrone sulfate acts as a pool of estrone which can be converted as needed to the more active estradiol.
# Synthesis
Estrone is synthesized via aromatase from androstenedione, a derivative of progesterone. The conversion consists of the de-methylation of C-19 and the aromaticity of the 'A' ring. This reaction is similar to the conversion of testosterone to estradiol.
# Additional images
- Androstenedione converting to estrone.
- Steroidogenesis
Template:Sex hormones
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Aquest | |
7125085d06298f0338592bea636a67f92cbcc9f2 | wikidoc | Arbidol | Arbidol
Arbidol) is an antiviral drug manufactured by Masterlek in Moscow, Russia.
Chemically, Arbidol features an indole core, functionalized at all positions but one with different substituents.
# Uses
It is an alternative to Tamiflu (manufactured by Roche Pharmaceuticals) used in the fight against avian influenza. Its antiviral inhibitory effect is still being tested and the current results range from being well accepted in pharmaceutical industry to accepted with a dose of suspicion.
The drug has mainly been tested in Russia and China, and has been shown to be effective against avian flu, suggesting it might be a more affordable and cost-effective drug than the widely used Tamiflu.
There is some evidence that it may be more effective at preventing infections from RNA viruses than from DNA viruses.
It has also been investigated as a candidate drug against hepatitis C.
# Mechanism of action
The drug exhibits immunomodulation as well as a specific anti-influenza action against the influenza A and influenza B viruses.
It prevents contact between the virus and host cells and penetration of virus particles into the cell by inhibiting the fusion of the virus lipid shell to the cell membranes.
It possesses interferon inducing action, by stimulating the humoral reaction and the phagocytic function of macrophages.
# Dosage forms
The drug is manufactured in the form of tablets and capsules, each tablet containing Arbidol® as its active ingredient (50 mg and 100 mg).
# Pharmacokinetics and usage
Side effects in children include sensitization to the drug. No known overdose cases have been reported and allergic reactions are limited to people with hypersensitivity. | Arbidol
Arbidol) is an antiviral drug manufactured by Masterlek in Moscow, Russia.
Chemically, Arbidol features an indole core, functionalized at all positions but one with different substituents.
# Uses
It is an alternative to Tamiflu (manufactured by Roche Pharmaceuticals) used in the fight against avian influenza. Its antiviral inhibitory effect is still being tested and the current results range from being well accepted in pharmaceutical industry to accepted with a dose of suspicion.
The drug has mainly been tested in Russia[1] and China,[2] and has been shown to be effective against avian flu,[3] suggesting it might be a more affordable and cost-effective drug than the widely used Tamiflu.
There is some evidence that it may be more effective at preventing infections from RNA viruses than from DNA viruses.[4]
It has also been investigated as a candidate drug against hepatitis C.[5]
# Mechanism of action
The drug exhibits immunomodulation[6] as well as a specific anti-influenza action against the influenza A and influenza B viruses.
It prevents contact between the virus and host cells and penetration of virus particles into the cell by inhibiting the fusion of the virus lipid shell to the cell membranes. [7]
It possesses interferon inducing action, by stimulating the humoral reaction and the phagocytic function of macrophages.
# Dosage forms
The drug is manufactured in the form of tablets and capsules, each tablet containing Arbidol® as its active ingredient (50 mg and 100 mg).
# Pharmacokinetics and usage
Side effects in children include sensitization to the drug. No known overdose cases have been reported and allergic reactions are limited to people with hypersensitivity. | https://www.wikidoc.org/index.php/Arbidol | |
2444a0e380afafd0140ba0f638dbc3f09018b52e | wikidoc | Arc eye | Arc eye
# Overview
Arc eye, also known as arc flash, welder's flash, corneal flash burns, or flash burns, is a painful ocular condition sometimes experienced by welders who have failed to use adequate eye protection. It can also occur due to light from tanning beds, light reflected from snow (known as snow blindness), water or sand. The intense ultraviolet light emitted by the arc causes a superficial and painful keratitis.
Symptoms tend to occur a number of hours after exposure and typically resolve spontaneously within 36 hours. The sensation has been described as having sand poured into the eyes.
This phenomenon results from intense levels of illumination by ultraviolet light, different than that of more common over-illumination found in many factories and offices.
# Signs
- Intense lacrimation
- Blepharospasm
- Photophobia
- Fluorescein dye staining will reveal corneal ulcers under blue light
- Constricted pupils note: this symptom may last as long as 96 to 128 hours in some cases.
# Management
- Instill topical anaesthesia
- Inspect the cornea for any foreign body
- Patch the worse of the two eyes and prescribe analgesia
- Topical antibiotics in the form of eye drops or eye ointment or both should be prescribed for prophylaxis against infection | Arc eye
Template:DiseaseDisorder infobox
# Overview
Arc eye, also known as arc flash, welder's flash, corneal flash burns, or flash burns, is a painful ocular condition sometimes experienced by welders who have failed to use adequate eye protection. It can also occur due to light from tanning beds, light reflected from snow (known as snow blindness), water or sand. The intense ultraviolet light emitted by the arc causes a superficial and painful keratitis.
Symptoms tend to occur a number of hours after exposure and typically resolve spontaneously within 36 hours. The sensation has been described as having sand poured into the eyes.
This phenomenon results from intense levels of illumination by ultraviolet light, different than that of more common over-illumination found in many factories and offices.
# Signs
- Intense lacrimation
- Blepharospasm
- Photophobia
- Fluorescein dye staining will reveal corneal ulcers under blue light
- Constricted pupils note: this symptom may last as long as 96 to 128 hours in some cases.
# Management
- Instill topical anaesthesia
- Inspect the cornea for any foreign body
- Patch the worse of the two eyes and prescribe analgesia
- Topical antibiotics in the form of eye drops or eye ointment or both should be prescribed for prophylaxis against infection | https://www.wikidoc.org/index.php/Arc_eye | |
d07d041e2a8973eb7b5837d3a5984d4ff411460f | wikidoc | Archaea | Archaea
# Overview
The Archaea (Template:IPA), or archaebacteria, are a major group of microorganisms. Like bacteria, archaea are single-celled organisms that lack nuclei and are therefore prokaryotes, classified in kingdom Monera in the traditional five-kingdom taxonomy. Although there is still uncertainty in the phylogeny, Archaea, Eukaryota and Bacteria are the fundamental classifications of what is called the three-domain system. Although their prokaryotic features are diagnostic of that clade, archaea are more closely related to eukaryotes than to bacteria. To account for this, archaeans and eukaryotes are grouped together in the clade Neomura, which is thought to have arisen from gram-positive bacteria. Archaea were originally described in extreme environments, but have since been found in all habitats and may contribute up to 20% of total biomass.
A single individual or species from this domain is called an archaeon (sometimes spelled "archeon"), while the adjectival form is archaeal or archaean. The etymology is Greek, from αρχαία meaning "ancient ones".
# Habitats
Multiple archaeans are extremophiles, and some would say this is their ecological niche. They can survive high temperatures, often above 100°C, as found in geysers, black smokers, and oil wells. Some are found in very cold habitats and others in highly saline, acidic, or alkaline water. Mesophiles favor milder conditions in marshland, sewage and soil. Many methanogenic archaea are found in the digestive tracts of animals such as ruminants, termites, and humans. As of 2007, no clear examples of archaeal pathogens are known, although a relationship has been proposed between the presence of some methanogens and human periodontal disease.
Archaea are commonly placed into three physiological groups. These are the halophiles, thermophiles and acidophiles. These groups are not necessarily comprehensive or monophyletic, nor even mutually exclusive. Nonetheless, they are a useful starting point for ecological studies. Halophiles, including the genus Halobacterium, live in extremely saline environments and start outnumbering their bacterial counterparts at salinities greater than 20-25%. These can be found in sediments or in the intestines of animals. Thermophiles live in places that have high temperatures, such as hot springs. Where optimal growth occurs at greater than 80°C, the archaeon is a hyperthermophyle, and the highest recorded temperature survived was 121°C. Although thermophilic bacteria predominate at some high temperatures, archaea generally have the edge when acidity exceeds pH 5. True acidophiles withstand pH 0 and below.
Recently, several studies have shown that archaea exist not only in mesophilic and thermophilic environments but are also present, sometimes in high numbers, at low temperatures as well. It is increasingly becoming recognised that methanogens are commonly present in low-temperature environments such as cold sediments. Some studies have even suggested that at these temperatures the pathway by which methanogenesis occurs may change due to the thermodynamic constraints imposed by low temperatures. Perhaps even more significant are the large numbers of archaea found throughout most of the world's oceans, a predominantly cold environment. These archaea, which belong to several deeply branching lineages unrelated to those previously known, can be present in extremely high numbers (up to 40% of the microbial biomass) although almost none have been isolated in pure culture. Currently we have almost no information regarding the physiology of these organisms, meaning that their effects on global biogeochemical cycles remain unknown. One recent study has shown, however, that one group of marine crenarchaeota are capable of nitrification, a trait previously unknown among the archaea.
# History of archaean microbiology
Archaea were identified in 1977 by Carl Woese and George E. Fox as being a separate branch based on their separation from other prokaryotes on 16S rRNA phylogenetic trees. These two groups were originally named the Archaebacteria and Eubacteria, treated as kingdoms or subkingdoms, which Woese and Fox termed Urkingdoms. Woese argued that they represented fundamentally different branches of living things. He later renamed the groups Archaea and Bacteria to emphasize this, and argued that together with Eukarya they compose three Domains of living organisms.
# Morphology and physiology
## Size and shape
Individual archaeans range from 0.1 μm to over 15 μm in diameter, and some form aggregates or filaments up to 200 μm in length. They occur in various shapes, such as spherical, rod-shape, spiral, lobed, or rectangular. Archaea have no murein in their cell walls. Recently, a species of flat, square archaean that lives in hypersaline pools has been discovered.
## Comparison of archaeal, bacterial and eukaryotic cells
Archaea are similar to other prokaryotes in most aspects of cell structure and metabolism. However, their genetic transcription and translation — the two central processes in molecular biology — do not show many typical bacterial features, and are in many aspects similar to those of eukaryotes. For instance, archaeal translation uses eukaryotic-like initiation and elongation factors, and their transcription involves TATA Binding Proteins and TFIIB as in eukaryotes. Many archaeal tRNA and rRNA genes harbor unique archaeal introns which are neither like eukaryotic introns, nor like bacterial (type I and type II etc which can "home") introns.
Several other characteristics also set the Archaea apart. Like bacteria and eukaryotes, archaea possess glycerol-based phospholipids. However, three features of the archaeal lipids are unusual:
- The archaeal lipids are unique because the stereochemistry of the glycerol is the reverse of that found in bacteria and eukaryotes. This is strong evidence for a different biosynthetic pathway.
- Most bacteria and eukaryotes have membranes composed mainly of glycerol-ester lipids, whereas archaea have membranes composed of glycerol-ether lipids. Even when bacteria have ether-linked lipids, the stereochemistry of the glycerol is the bacterial form. These differences may be an adaptation on the part of Archaea to hyperthermophily. However, it is worth noting that even mesophilic archaea have ether-linked lipids.
- Archaeal lipids are based upon the isoprenoid sidechain. This is a five-carbon unit that is also common in rubber and as a component of some bacterial and eukaryotic vitamins. However, only the archaea incorporate these compounds into their cellular lipids, frequently as C-20 (four monomers) or C-40 (eight monomers) side-chains. In some archaea, the C-40 isoprenoid side-chain is long enough to span the membrane, forming a monolayer for a cell membrane with glycerol phosphate moieties on both ends. Although dramatic, this adaptation is most common in the extremely thermophilic archaea.
## Cell wall and flagella
Although not unique, archaeal cell walls are also unusual. For instance, in most archaea they are formed by surface-layer proteins or an S-layer. S-layers are common in bacteria, where they serve as the sole cell-wall component in some organisms (like the Planctomyces) or an outer layer in many organisms with peptidoglycan. With the exception of one group of methanogens, archaea lack a peptidoglycan wall (and in the case of the exception, the peptidoglycan is very different from the type found in bacteria).
Archaeans also have flagella that are notably different in composition and development from the superficially similar flagella of bacteria. The bacterial flagellum is a modified type III secretion system, while archeal flagella resemble type IV pilli which use a sec dependent secretion system somewhat similar to but different from type II secretion system.
# Metabolism
Archaea exhibit a variety of different types of metabolism; there are nitrifiers, methanogens and anaerobic methane oxidisers. Methanogens live in anaerobic environments and produce methane. Of note are the halobacteria, which use light to produce energy. Although no archaea conduct photosynthesis with an electron transport chain, light-activated ion pumps like bacteriorhodopsin and halorhodopsin play a role in generating ion gradients, which are harnessed into adenosine triphosphate (ATP).
# Genetics and propagation
Archaea have one circular chromosome although up to 30% of their genetic material may be contained in plasmids, as evidenced by comparisons of GC content. Archaea can reproduce by binary and multiple fission, fragmentation, and budding.
# Phylogeny
Archaea are divided into two main groups based on rRNA trees, the Euryarchaeota and Crenarchaeota. Three other groups have been tentatively created for certain environmental samples, the peculiar species Nanoarchaeum equitans, discovered in 2002 by Karl Stetter, and the Archael Richmond Mine Acidophilic Nanoorganisms (ARMAN) groups discovered by Brett Baker, but their affinities are uncertain.
Woese argued that the bacteria, archaea, and eukaryotes each represent a primary line of descent that diverged early on from an ancestral progenote with poorly developed genetic machinery. Later he treated these groups formally as domains, each comprising several kingdoms. This division has become very popular, although the idea of the progenote itself is not generally supported. Some biologists, however, have argued that the archaebacteria and eukaryotes arose from specialized eubacteria.
The relationship between Archaea and Eukarya remains an important problem. Aside from the similarities noted above, many genetic trees group the two together. Some place eukaryotes closer to Euryarchaeota than Crenarchaeota are, although the membrane chemistry suggests otherwise. However, the discovery of archaean-like genes in certain bacteria, such as Thermotoga, makes their relationship difficult to determine, as horizontal gene transfer may have occurred. Some have suggested that eukaryotes arose through fusion of an archaean and eubacterium, which became the nucleus and cytoplasm, which accounts for various genetic similarities but runs into difficulties explaining cell structure.
Single gene sequencing for systematics has led to whole genome sequencing; by January, 2007, 31 archaeal genomes have been completed with 29 partially completed.
## Origin and early evolution
The Archaea should not be confused with the geological term Archean eon, also known as the Archeozoic era. This refers to the primordial period of earth history when Archaea and Bacteria were the only cellular organisms living on the planet. Probable fossils of these microbes have been dated to almost 3.5 billion years ago, and the remains of lipids that may be either archaean or eukaryotic have been detected in shales dating from 2.7 billion years ago.
The last common ancestor of Bacteria and Archaea was probably a non-methanogenic thermophile, raising the possibility that lower temperatures are extreme environments in archaeal terms, and organisms that can survive in cooler environments evolved later on. | Archaea
# Overview
The Archaea (Template:IPA), or archaebacteria, are a major group of microorganisms. Like bacteria, archaea are single-celled organisms that lack nuclei and are therefore prokaryotes, classified in kingdom Monera in the traditional five-kingdom taxonomy. Although there is still uncertainty in the phylogeny, Archaea, Eukaryota and Bacteria are the fundamental classifications of what is called the three-domain system. Although their prokaryotic features are diagnostic of that clade, archaea are more closely related to eukaryotes than to bacteria. To account for this, archaeans and eukaryotes are grouped together in the clade Neomura, which is thought to have arisen from gram-positive bacteria. Archaea were originally described in extreme environments, but have since been found in all habitats and may contribute up to 20% of total biomass.[1]
A single individual or species from this domain is called an archaeon (sometimes spelled "archeon"),[2] while the adjectival form is archaeal or archaean. The etymology is Greek, from αρχαία meaning "ancient ones".
# Habitats
Multiple archaeans are extremophiles, and some would say this is their ecological niche.[2] They can survive high temperatures, often above 100°C, as found in geysers, black smokers, and oil wells. Some are found in very cold habitats and others in highly saline, acidic, or alkaline water. Mesophiles favor milder conditions in marshland, sewage and soil. Many methanogenic archaea are found in the digestive tracts of animals such as ruminants, termites, and humans. As of 2007, no clear examples of archaeal pathogens are known,[3][4] although a relationship has been proposed between the presence of some methanogens and human periodontal disease.[5]
Archaea are commonly placed into three physiological groups. These are the halophiles, thermophiles and acidophiles. These groups are not necessarily comprehensive or monophyletic, nor even mutually exclusive. Nonetheless, they are a useful starting point for ecological studies. Halophiles, including the genus Halobacterium, live in extremely saline environments and start outnumbering their bacterial counterparts at salinities greater than 20-25%.[2] These can be found in sediments or in the intestines of animals.[citation needed] Thermophiles live in places that have high temperatures, such as hot springs. Where optimal growth occurs at greater than 80°C, the archaeon is a hyperthermophyle, and the highest recorded temperature survived was 121°C. Although thermophilic bacteria predominate at some high temperatures, archaea generally have the edge when acidity exceeds pH 5. True acidophiles withstand pH 0 and below.[2]
Recently, several studies have shown that archaea exist not only in mesophilic and thermophilic environments but are also present, sometimes in high numbers, at low temperatures as well. It is increasingly becoming recognised that methanogens are commonly present in low-temperature environments such as cold sediments. Some studies have even suggested that at these temperatures the pathway by which methanogenesis occurs may change due to the thermodynamic constraints imposed by low temperatures. Perhaps even more significant are the large numbers of archaea found throughout most of the world's oceans, a predominantly cold environment. These archaea, which belong to several deeply branching lineages unrelated to those previously known, can be present in extremely high numbers (up to 40% of the microbial biomass) although almost none have been isolated in pure culture.[6] Currently we have almost no information regarding the physiology of these organisms, meaning that their effects on global biogeochemical cycles remain unknown. One recent study has shown, however, that one group of marine crenarchaeota are capable of nitrification, a trait previously unknown among the archaea.[7]
# History of archaean microbiology
Archaea were identified in 1977 by Carl Woese and George E. Fox as being a separate branch based on their separation from other prokaryotes on 16S rRNA phylogenetic trees.[8] These two groups were originally named the Archaebacteria and Eubacteria, treated as kingdoms or subkingdoms, which Woese and Fox termed Urkingdoms. Woese argued that they represented fundamentally different branches of living things. He later renamed the groups Archaea and Bacteria to emphasize this, and argued that together with Eukarya they compose three Domains of living organisms.[9]
# Morphology and physiology
## Size and shape
Individual archaeans range from 0.1 μm to over 15 μm in diameter, and some form aggregates or filaments up to 200 μm in length. They occur in various shapes, such as spherical, rod-shape, spiral, lobed, or rectangular. Archaea have no murein in their cell walls. Recently, a species of flat, square archaean that lives in hypersaline pools has been discovered.[10]
## Comparison of archaeal, bacterial and eukaryotic cells
Archaea are similar to other prokaryotes in most aspects of cell structure and metabolism. However, their genetic transcription and translation — the two central processes in molecular biology — do not show many typical bacterial features, and are in many aspects similar to those of eukaryotes. For instance, archaeal translation uses eukaryotic-like initiation and elongation factors, and their transcription involves TATA Binding Proteins and TFIIB as in eukaryotes. Many archaeal tRNA and rRNA genes harbor unique archaeal introns which are neither like eukaryotic introns, nor like bacterial (type I and type II etc which can "home") introns.
Several other characteristics also set the Archaea apart. Like bacteria and eukaryotes, archaea possess glycerol-based phospholipids. However, three features of the archaeal lipids are unusual:[11]
- The archaeal lipids are unique because the stereochemistry of the glycerol is the reverse of that found in bacteria and eukaryotes. This is strong evidence for a different biosynthetic pathway.
- Most bacteria and eukaryotes have membranes composed mainly of glycerol-ester lipids, whereas archaea have membranes composed of glycerol-ether lipids. Even when bacteria have ether-linked lipids, the stereochemistry of the glycerol is the bacterial form. These differences may be an adaptation on the part of Archaea to hyperthermophily. However, it is worth noting that even mesophilic archaea have ether-linked lipids.
- Archaeal lipids are based upon the isoprenoid sidechain. This is a five-carbon unit that is also common in rubber and as a component of some bacterial and eukaryotic vitamins. However, only the archaea incorporate these compounds into their cellular lipids, frequently as C-20 (four monomers) or C-40 (eight monomers) side-chains. In some archaea, the C-40 isoprenoid side-chain is long enough to span the membrane, forming a monolayer for a cell membrane with glycerol phosphate moieties on both ends. Although dramatic, this adaptation is most common in the extremely thermophilic archaea.
## Cell wall and flagella
Although not unique, archaeal cell walls are also unusual. For instance, in most archaea they are formed by surface-layer proteins or an S-layer. S-layers are common in bacteria, where they serve as the sole cell-wall component in some organisms (like the Planctomyces) or an outer layer in many organisms with peptidoglycan. With the exception of one group of methanogens, archaea lack a peptidoglycan wall (and in the case of the exception, the peptidoglycan is very different from the type found in bacteria).[12]
Archaeans also have flagella that are notably different in composition and development from the superficially similar flagella of bacteria. The bacterial flagellum is a modified type III secretion system, while archeal flagella resemble type IV pilli which use a sec dependent secretion system somewhat similar to but different from type II secretion system.
# Metabolism
Archaea exhibit a variety of different types of metabolism; there are nitrifiers, methanogens and anaerobic methane oxidisers.[2] Methanogens live in anaerobic environments and produce methane. Of note are the halobacteria, which use light to produce energy. Although no archaea conduct photosynthesis with an electron transport chain, light-activated ion pumps like bacteriorhodopsin and halorhodopsin play a role in generating ion gradients, which are harnessed into adenosine triphosphate (ATP).
# Genetics and propagation
Archaea have one circular chromosome although up to 30% of their genetic material may be contained in plasmids, as evidenced by comparisons of GC content. Archaea can reproduce by binary and multiple fission, fragmentation, and budding.
# Phylogeny
Archaea are divided into two main groups based on rRNA trees, the Euryarchaeota and Crenarchaeota. Three other groups have been tentatively created for certain environmental samples, the peculiar species Nanoarchaeum equitans, discovered in 2002 by Karl Stetter[13], and the Archael Richmond Mine Acidophilic Nanoorganisms (ARMAN) groups discovered by Brett Baker, but their affinities are uncertain.[14]
Woese argued that the bacteria, archaea, and eukaryotes each represent a primary line of descent that diverged early on from an ancestral progenote with poorly developed genetic machinery. Later he treated these groups formally as domains, each comprising several kingdoms. This division has become very popular, although the idea of the progenote itself is not generally supported. Some biologists, however, have argued that the archaebacteria and eukaryotes arose from specialized eubacteria.
The relationship between Archaea and Eukarya remains an important problem. Aside from the similarities noted above, many genetic trees group the two together. Some place eukaryotes closer to Euryarchaeota than Crenarchaeota are, although the membrane chemistry suggests otherwise. However, the discovery of archaean-like genes in certain bacteria, such as Thermotoga, makes their relationship difficult to determine, as horizontal gene transfer may have occurred.[15] Some have suggested that eukaryotes arose through fusion of an archaean and eubacterium, which became the nucleus and cytoplasm, which accounts for various genetic similarities but runs into difficulties explaining cell structure.[16]
Single gene sequencing for systematics has led to whole genome sequencing; by January, 2007, 31 archaeal genomes have been completed with 29 partially completed.[17]
## Origin and early evolution
The Archaea should not be confused with the geological term Archean eon, also known as the Archeozoic era. This refers to the primordial period of earth history when Archaea and Bacteria were the only cellular organisms living on the planet.[18][19] Probable fossils of these microbes have been dated to almost 3.5 billion years ago,[20] and the remains of lipids that may be either archaean or eukaryotic have been detected in shales dating from 2.7 billion years ago.[21]
The last common ancestor of Bacteria and Archaea was probably a non-methanogenic thermophile, raising the possibility that lower temperatures are extreme environments in archaeal terms, and organisms that can survive in cooler environments evolved later on.[22] | https://www.wikidoc.org/index.php/Archae | |
08c231ebe5f13f5952fbc3bba38217f6f1f74769 | wikidoc | Archean | Archean
The Archean (Template:PronEng, also spelled Archaean, formerly called the Archaeozoic (Template:IPA), also spelled Archeozoic or Archæozoic) is a geologic eon before the Proterozoic and Paleoproterozoic, ending 2.5 Ga (billion years ago). Instead of being based on stratigraphy, this date is defined chronometrically. The lower boundary (starting point) has not been officially recognized by the International Commission on Stratigraphy, but it is usually set to 3.8 Ga, at the end of the Hadean eon.
# Archean Earth
At the beginning of the Archean, the Earth's heat flow was nearly three times higher than it is today, and was still twice the current level by the beginning of the Proterozoic. The extra heat may have been remnant heat from the planetary accretion, partly heat of formation of the iron core, and partially caused by greater radiogenic heat production from short-lived radionuclides such as uranium-235.
The majority of Archean rocks which exist are metamorphic and igneous rocks, the bulk of the latter being intrusive.Template:Clarifyme Volcanic activity was considerably higher than today, with numerous hot spots, and rift valleys, and eruption of unusual lavas such as komatiite. Intrusive igneous rocks such as great melt sheets and voluminous plutonic masses of granite, diorite, ultramafic to mafic layered intrusions, anorthosites and monzonites known as sanukitoids predominate throughout the crystalline cratonic remnants of the Archean crust which exist today.
The Earth of the early Archean may have had a different tectonic style. Some scientists think that, because the Earth was hotter, plate tectonic activity was more vigorous than it is today, resulting in a much greater rate of recycling of crustal material. This may have prevented cratonisation and continent formation until the mantle cooled and convection slowed down. Others argue that the sub continental lithospheric mantle is too buoyant to subduct and that the lack of Archean rocks is a function of erosion by subsequent tectonic events. The question of whether or not plate tectonic activity existed in the Archean is an active area of modern geoscientific research.
There were no large continents until late in the Archean; small protocontinents were the norm, prevented from coalescing into larger units by the high rate of geologic activity. These felsic protocontinents probably formed at hotspots rather than subduction zones, from a variety of sources: igneous differentiation of mafic rocks to produce intermediate and felsic rocks, mafic magma melting more felsic rocks and forcing granitization of intermediate rocks, partial melting of mafic rock, and from the metamorphic alteration of felsic sedimentary rocks. Such continental fragments may not have been preserved if they were not buoyant enough or fortunate enough to avoid energetic subduction zones.
Another explanation for a general lack of early Archean rocks greater than 3800 Ma is the amount of extrasolar debris present within the early solar system. Even after planetary formation, considerable volumes of large asteroids and meteorites still existed, and bombarded the early Earth until approximately 3800 Ma. A barrage of particularly large impactors known as the late heavy bombardment may have prevented any large crustal fragments from forming by literally shattering the early protocontinents.
## Archean palaeoenvironment
The Archean atmosphere apparently lacked free oxygen. Temperatures appear to have been near modern levels even within 500 Ma of Earth's formation, with liquid water present, due to the presence of sedimentary rocks within certain highly deformed gneisses. Astronomers think that the sun was about one-third dimmer, which may have contributed to lower global temperatures than otherwise expected. This is thought to reflect larger amounts of greenhouse gases than later in the Earth's history.
By the end of the Archaean c. 2600 Mya, plate tectonic activity may have been similar to that of the modern Earth; there are well preserved sedimentary basins and evidence of volcanic arcs, intracontinental rifts, continent-continent collisions and widespread globe-spanning orogenic events suggesting the assembly and destruction of one and perhaps several supercontinents. Liquid water was prevalent, and deep oceanic basins are known to have existed by the presence of banded iron formations, chert beds, chemical sediments and pillow basalts.
# Archean geology
Although a few mineral grains are known that are older, the oldest rock formations exposed on the surface of the Earth are Archean or slightly older. Archean rocks are known from Greenland, the Canadian Shield, the Baltic shield, Scotland, India, Brazil, western Australia, and southern Africa. Although the first continents formed during this eon, rock of this age makes up only 7% of the world's current cratons; even allowing for erosion and destruction of past formations, evidence suggests that only 5-40% of the present continental crust formed during the Archean.
In contrast to the Proterozoic, Archean rocks are often heavily metamorphized deep-water sediments, such as graywackes, mudstones, volcanic sediments, and banded iron formations. Carbonate rocks are rare, indicating that the oceans were more acidic due to dissolved carbon dioxide than during the Proterozoic. Greenstone belts are typical Archean formations, consisting of alternating high and low-grade metamorphic rocks. The high-grade rocks were derived from volcanic island arcs, while the low-grade metamorphic rocks represent deep-sea sediments eroded from the neighboring island arcs and deposited in a forearc basin. In short, greenstone belts represent sutured protocontinents.
# Archean life
Fossils of cyanobacterial mats (stromatolites) are found throughout the Archean—becoming especially common late in the eon—while a few probable bacterial fossils are known from chert beds. In addition to the domain Bacteria (once known as Eubacteria), microfossils of the extremophilic domain Archaea have also been identified.
Life was probably present throughout the Archean, but may have been limited to simple non-nucleated single-celled organisms, called Prokaryota (and formerly known as Monera); there are no known eukaryotic fossils, though they might have evolved during the Archean and simply not left any fossils. However, no fossil evidence yet exists for ultramicroscopic intracellular replicators such as viruses. | Archean
The Archean (Template:PronEng, also spelled Archaean, formerly called the Archaeozoic (Template:IPA), also spelled Archeozoic or Archæozoic) is a geologic eon before the Proterozoic and Paleoproterozoic, ending 2.5 Ga (billion years ago). Instead of being based on stratigraphy, this date is defined chronometrically. The lower boundary (starting point) has not been officially recognized by the International Commission on Stratigraphy, but it is usually set to 3.8 Ga, at the end of the Hadean eon.
# Archean Earth
At the beginning of the Archean, the Earth's heat flow was nearly three times higher than it is today, and was still twice the current level by the beginning of the Proterozoic. The extra heat may have been remnant heat from the planetary accretion, partly heat of formation of the iron core, and partially caused by greater radiogenic heat production from short-lived radionuclides such as uranium-235.
The majority of Archean rocks which exist are metamorphic and igneous rocks, the bulk of the latter being intrusive.Template:Clarifyme Volcanic activity was considerably higher than today, with numerous hot spots, and rift valleys, and eruption of unusual lavas such as komatiite. Intrusive igneous rocks such as great melt sheets and voluminous plutonic masses of granite, diorite, ultramafic to mafic layered intrusions, anorthosites and monzonites known as sanukitoids predominate throughout the crystalline cratonic remnants of the Archean crust which exist today.
The Earth of the early Archean may have had a different tectonic style. Some scientists think that, because the Earth was hotter, plate tectonic activity was more vigorous than it is today, resulting in a much greater rate of recycling of crustal material. This may have prevented cratonisation and continent formation until the mantle cooled and convection slowed down. Others argue that the sub continental lithospheric mantle is too buoyant to subduct and that the lack of Archean rocks is a function of erosion by subsequent tectonic events. The question of whether or not plate tectonic activity existed in the Archean is an active area of modern geoscientific research. [1]
There were no large continents until late in the Archean; small protocontinents were the norm, prevented from coalescing into larger units by the high rate of geologic activity. These felsic protocontinents probably formed at hotspots rather than subduction zones, from a variety of sources: igneous differentiation of mafic rocks to produce intermediate and felsic rocks, mafic magma melting more felsic rocks and forcing granitization of intermediate rocks, partial melting of mafic rock, and from the metamorphic alteration of felsic sedimentary rocks. Such continental fragments may not have been preserved if they were not buoyant enough or fortunate enough to avoid energetic subduction zones.[2]
Another explanation for a general lack of early Archean rocks greater than 3800 Ma is the amount of extrasolar debris present within the early solar system. Even after planetary formation, considerable volumes of large asteroids and meteorites still existed, and bombarded the early Earth until approximately 3800 Ma. A barrage of particularly large impactors known as the late heavy bombardment may have prevented any large crustal fragments from forming by literally shattering the early protocontinents.
## Archean palaeoenvironment
The Archean atmosphere apparently lacked free oxygen. Temperatures appear to have been near modern levels even within 500 Ma of Earth's formation, with liquid water present, due to the presence of sedimentary rocks within certain highly deformed gneisses. Astronomers think that the sun was about one-third dimmer, which may have contributed to lower global temperatures than otherwise expected. This is thought to reflect larger amounts of greenhouse gases than later in the Earth's history.
By the end of the Archaean c. 2600 Mya, plate tectonic activity may have been similar to that of the modern Earth; there are well preserved sedimentary basins and evidence of volcanic arcs, intracontinental rifts, continent-continent collisions and widespread globe-spanning orogenic events suggesting the assembly and destruction of one and perhaps several supercontinents. Liquid water was prevalent, and deep oceanic basins are known to have existed by the presence of banded iron formations, chert beds, chemical sediments and pillow basalts.
# Archean geology
Although a few mineral grains are known that are older, the oldest rock formations exposed on the surface of the Earth are Archean or slightly older. Archean rocks are known from Greenland, the Canadian Shield, the Baltic shield, Scotland, India, Brazil, western Australia, and southern Africa. Although the first continents formed during this eon, rock of this age makes up only 7% of the world's current cratons; even allowing for erosion and destruction of past formations, evidence suggests that only 5-40% of the present continental crust formed during the Archean.[3]
In contrast to the Proterozoic, Archean rocks are often heavily metamorphized deep-water sediments, such as graywackes, mudstones, volcanic sediments, and banded iron formations. Carbonate rocks are rare, indicating that the oceans were more acidic due to dissolved carbon dioxide than during the Proterozoic.[4] Greenstone belts are typical Archean formations, consisting of alternating high and low-grade metamorphic rocks. The high-grade rocks were derived from volcanic island arcs, while the low-grade metamorphic rocks represent deep-sea sediments eroded from the neighboring island arcs and deposited in a forearc basin. In short, greenstone belts represent sutured protocontinents.[5]
# Archean life
Fossils of cyanobacterial mats (stromatolites) are found throughout the Archean—becoming especially common late in the eon—while a few probable bacterial fossils are known from chert beds.[6] In addition to the domain Bacteria (once known as Eubacteria), microfossils of the extremophilic domain Archaea have also been identified.
Life was probably present throughout the Archean, but may have been limited to simple non-nucleated single-celled organisms, called Prokaryota (and formerly known as Monera); there are no known eukaryotic fossils, though they might have evolved during the Archean and simply not left any fossils.[7] However, no fossil evidence yet exists for ultramicroscopic intracellular replicators such as viruses. | https://www.wikidoc.org/index.php/Archean | |
a4062fd11874571183b145efcd9cde7bf62b6459 | wikidoc | Argyria | Argyria
Argyria (ISV from Greek: αργύρος argyros silver + -ia) is an extremely rare condition caused by the ingestion of elemental silver, silver dust or silver compounds. The most dramatic effect of argyria is that the skin is colored blue or bluish-grey. Argyria may be found as generalized argyria or local argyria. Argyrosis is the corresponding condition related to the eye. The condition is believed to be permanent, but laser therapy may be helpful. Most recent cases are due to consumption of home-made silver products, and almost all of these cases, in turn, involved production techniques which are generally considered incorrect by colloidal-silver producers.
# History
Since at least the early part of the 20th century, doctors have known that silver or silver compounds can cause some areas of the skin and other body tissues to turn gray or blue-gray. Argyria occurs in people who eat or breathe in silver over a long period (several months to many years). A single exposure to a silver compound may also cause silver to be deposited in the skin and in other parts of the body; however, this is not known to be harmful. It is likely that many exposures to silver are necessary to develop argyria. Once argyria develops, it is generally believed to be permanent, though some have claimed to have reversed it. However, the condition is thought to be only a "cosmetic problem". Most doctors and scientists believe that the discoloration of the skin seen in argyria is the most serious health effect of silver (in non-extreme doses).
Reports of cases of argyria and an EPA statement suggest that gram amounts (from 1 to 4 grams) of silver or a silver compound taken in medication in small doses over several months may cause argyria in some humans. People who work in factories that manufacture silver can also breathe in silver or its compounds. In the past, some of these workers have become argyric. However, the level of silver in the air and the length of exposure that caused argyria in these workers is not known. It is also not known what level of silver causes breathing problems, lung and throat irritation, or stomach pain in people. Studies in rats show that drinking water containing very large amounts of silver (9.8 grams of silver per U.S. gallon water or 2.6 grams per liter) is likely to be life-threatening.
Argyria that covers the entire body is not seen following skin contact with silver compounds, although the skin may change color where it touches the silver. However, many people who have used skin creams containing silver compounds such as silver nitrate and silver sulfadiazine have not reported health problems from the silver in the medicine. In one animal study, a strong solution of silver nitrate (81 milligrams silver nitrate per liter of water) applied to the skin of guinea pigs for 28 days did not cause the animals to die; however, it did cause the guinea pigs to stop gaining weight normally. It is not known if this would happen to people if they were exposed the same way.
A recent prominent case was that of Stan Jones, of Montana, a Libertarian candidate for the United States Senate in 2002 and 2006. Jones acquired argyria through consumption of a home-made silver product which he made due to fears that the Year 2000 problem would make antibiotics unavailable. He later revealed that he had used many techniques which are generally considered unwise by colloidal-silver producers, some of which were: (1) The use of mineral-rich well water, which likely caused the production of various, unpredictable silver compounds; (2) the addition of salt as an accelerant, which likely caused the production of the compound, silver chloride; (3) unusually long production times, which likely produced unusually high concentrations; and (4) the lack of filtering, which likely caused him to ingest a lot of non-soluble silver compounds. The peculiar colouration of his skin was featured prominently in media coverage of his unsuccessful campaign, though Jones believes that the best-known photo was "doctored". Jones promised that he was not using his silvery complexion as a gimmick. In fact, he continues to promote the use of colloidal silver as a home remedy. He has said that his good health, minus the unusual skin tone, is the result of his use of colloidal silver. | Argyria
Template:Search infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Argyria (ISV from Greek: αργύρος argyros silver + -ia) is an extremely rare condition caused by the ingestion of elemental silver, silver dust or silver compounds. The most dramatic effect of argyria is that the skin is colored blue or bluish-grey. Argyria may be found as generalized argyria or local argyria. Argyrosis is the corresponding condition related to the eye. The condition is believed to be permanent, but laser therapy may be helpful. Most recent cases are due to consumption of home-made silver products, and almost all of these cases, in turn, involved production techniques which are generally considered incorrect by colloidal-silver producers.
# History
Since at least the early part of the 20th century, doctors have known that silver or silver compounds can cause some areas of the skin and other body tissues to turn gray or blue-gray. Argyria occurs in people who eat or breathe in silver over a long period (several months to many years). A single exposure to a silver compound may also cause silver to be deposited in the skin and in other parts of the body; however, this is not known to be harmful. It is likely that many exposures to silver are necessary to develop argyria. Once argyria develops, it is generally believed to be permanent, though some have claimed to have reversed it[1]. However, the condition is thought to be only a "cosmetic problem". Most doctors and scientists believe that the discoloration of the skin seen in argyria is the most serious health effect of silver (in non-extreme doses).
Reports of cases of argyria and an EPA statement suggest that gram amounts (from 1 to 4 grams) of silver or a silver compound taken in medication in small doses over several months may cause argyria in some humans. People who work in factories that manufacture silver can also breathe in silver or its compounds. In the past, some of these workers have become argyric. However, the level of silver in the air and the length of exposure that caused argyria in these workers is not known. It is also not known what level of silver causes breathing problems, lung and throat irritation, or stomach pain in people. Studies in rats show that drinking water containing very large amounts of silver (9.8 grams of silver per U.S. gallon water or 2.6 grams per liter) is likely to be life-threatening.
Argyria that covers the entire body is not seen following skin contact with silver compounds, although the skin may change color where it touches the silver. However, many people who have used skin creams containing silver compounds such as silver nitrate and silver sulfadiazine have not reported health problems from the silver in the medicine. In one animal study, a strong solution of silver nitrate (81 milligrams silver nitrate per liter of water) applied to the skin of guinea pigs for 28 days did not cause the animals to die; however, it did cause the guinea pigs to stop gaining weight normally. It is not known if this would happen to people if they were exposed the same way.
A recent prominent case was that of Stan Jones, of Montana, a Libertarian candidate for the United States Senate in 2002 and 2006. Jones acquired argyria through consumption of a home-made silver product which he made due to fears that the Year 2000 problem would make antibiotics unavailable. He later revealed that he had used many techniques which are generally considered unwise by colloidal-silver producers, some of which were: (1) The use of mineral-rich well water, which likely caused the production of various, unpredictable silver compounds; (2) the addition of salt as an accelerant, which likely caused the production of the compound, silver chloride; (3) unusually long production times, which likely produced unusually high concentrations; and (4) the lack of filtering, which likely caused him to ingest a lot of non-soluble silver compounds[2]. The peculiar colouration of his skin was featured prominently in media coverage of his unsuccessful campaign, though Jones believes that the best-known photo[3] was "doctored"[2]. Jones promised that he was not using his silvery complexion as a gimmick. In fact, he continues to promote the use of colloidal silver as a home remedy[2]. He has said that his good health, minus the unusual skin tone, is the result of his use of colloidal silver[2]. | https://www.wikidoc.org/index.php/Argiria |
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