Journal ArticleDOI
Biomarkers of organophosphorus nerve agent exposure: comparison of phosphylated butyrylcholinesterase and phosphylated albumin after oxime therapy
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TLDR
Plasma samples obtained from an animal study aimed at improving therapy against nerve agent poisoning were used to compare the suitability of tyrosine and butyrylcholinesterase (BuChE) adducts as biomarkers of nerve agent exposure after treatment with therapeutic oximes.Abstract:
Organophosphorus nerve agents inhibit the activity of cholinesterases by phosphylation of the active site serine. In addition, sarin, cyclosarin, soman and tabun have been shown to phosphylate a tyrosine residue in albumin. Therapies against nerve agent poisoning include the use of oximes to reactivate inhibited cholinesterases by displacement of the phosphyl moiety and hence detectable levels of adducts with cholinesterases may be reduced. Adducts with tyrosine have been shown to be persistent in the guinea pig in the presence of oxime therapy. Plasma samples obtained from an animal study aimed at improving therapy against nerve agent poisoning were used to compare the suitability of tyrosine and butyrylcholinesterase (BuChE) adducts as biomarkers of nerve agent exposure after treatment with therapeutic oximes. Under the terms of the project licence, these samples could be collected only on death of the animal, which occurred within hours of exposure or when culled at 23 or 24 days. Tyrosine adducts were detected in all samples collected following intra-muscular administration of twice the LD50 dose of the respective nerve agent. Aged BuChE adducts were detected in samples collected within a few hours after administration of soman and tabun, but not after 23 or 24 days. No BuChE adducts were detected in animals exposed to sarin and cyclosarin where samples were collected only after 23 or 24 days.read more
Citations
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Recent Advances in the Treatment of Organophosphorous Poisonings
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Mice treated with chlorpyrifos or chlorpyrifos oxon have organophosphorylated tubulin in the brain and disrupted microtubule structures, suggesting a role for tubulin in neurotoxicity associated with exposure to organophosphorus agents.
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TL;DR: Microtubules from mice exposed to chlorpyrifos or to CPO have covalently modified amino acids and abnormal structure, suggesting disruption of microtubule function.
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Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for detection and identification of albumin phosphylation by organophosphorus pesticides and G- and V-type nerve agents.
TL;DR: Novel adducts of human serum albumin (HSA) are detected and identified by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and exhibits potential as a verification tool for high-dose exposure.
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Quantification of nerve agent adducts with albumin in rat plasma using liquid chromatography–isotope dilution tandem mass spectrometry
TL;DR: This sensitive method was successfully applied to the analysis of adducts in rat plasma after nerve agent exposure, and the results demonstrated the dose-effect relationships.
References
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Journal ArticleDOI
A new and rapid colorimetric determination of acetylcholinesterase activity.
TL;DR: A photometric method for determining acetylcholinesterase activity of tissue extracts, homogenates, cell suspensions, etc., has been described and Kinetic constants determined by this system for erythrocyte eholinesterases are presented.
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Application of gas chromatography-mass spectrometry and gas chromatography-tandem mass spectrometry to the analysis of chemical warfare samples, found to contain residues of the nerve agent sarin, sulphur mustard and their degradation products
TL;DR: Samples of clothing, grave debris, soil and munition fragments, collected from the Kurdish village of Birjinni, were analysed by GC-MS with selected ion monitoring (SIM) for traces of chemical warfare agents and their degradation products, providing the first documented unequivocal identification of nerve agent residues in environmental samples collected after a chemical attack.
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New method for retrospective detection of exposure to organophosphorus anticholinesterases : Application to alleged sarin victims of Japanese terrorists
TL;DR: The new procedure is applied to serum samples from victims of the Tokyo subway attack by the AUM Shinriyko sect and from an earlier incident at Matsumoto, finding that these victims had been exposed to an organophosphate with the structure PriO(CH3)P(O)X, presumably with X = F (sarin).
Journal ArticleDOI
Definitive evidence for the acute sarin poisoning diagnosis in the Tokyo subway.
Masataka Nagao,Takehiko Takatori,Yukimasa Matsuda,Makoto Nakajima,Hirotaro Iwase,Kimiharu Iwadate +5 more
TL;DR: In this article, a new method was developed to detect sarin hydrolysis products from erythrocytes of four victims of sarin poisoning resulting from the terrorist attack on the Tokyo subway.
Journal ArticleDOI
Retrospective detection of exposure to organophosphorus anti-cholinesterases: Mass spectrometric analysis of phosphylated human butyrylcholinesterase
A. Fidder,Albert G. Hulst,Daan Noort,R. de Ruiter,M.J. van der Schans,Hendrik P. Benschop,Jan P. Langenberg +6 more
TL;DR: A novel and general procedure is presented for detection of organophosphate-inhibited human butyrylcholinesterase (HuBuChE), which is based on electrospray tandem mass spectrometric analysis of phosphylated nonapeptides obtained after pepsin digestion of the enzyme.