New Method for Retrospective Detection of Exposure to Organophosphorus Anticholinesterases: Application to Alleged Sarin Victims of Japanese Terrorists

Polhuijs, Martine; Langenberg, J.P.; Benschop, H. P.

doi:10.1006/taap.1997.8243

Cited by 201 publications

(130 citation statements)

References 23 publications

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“…Fluoride ions reactivate the inhibited enzyme readily at pH 4, converting the OP moiety into the corresponding phosphofluoridate. Subsequent quantification of the latter product provides a reliable and highly sensitive method for detection of exposure to, or handling of, OPs such as nerve agents or pesticides [122]. This procedure was applied to serum samples from the victims of the Tokyo subway attack by the AUM Shinriyko sect and in an earlier incident at Matsumoto.…”

Section: Biochemistrymentioning

confidence: 99%

Organophosphorus poisoning and anaesthesia

1999

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SummaryOrganophosphorus compounds, used as insecticides and agents of chemical warfare, are a major global cause of health problems. These irreversible inhibitors of cholinesterase produce three wellrecognised clinical entities: the initial cholinergic phase, which is a medical emergency often requiring management in an intensive care unit; the intermediate syndrome, during which prolonged ventilatory care is necessary; and delayed polyneuropathy. In addition, disturbances of body temperature and endocrine function, electrolyte imbalances, immunological dysfunction and disorders of reproduction have been reported in animals and man. Vocal cord paralysis, pancreatitis, cardiac arrhythmias and a wide range of neuropsychiatric disorders are known to follow acute and chronic exposure to organophosphorus compounds. As a result of the inhibition of plasma cholinesterase, there can be increased sensitivity to drugs hydrolysed by this enzyme, e.g. suxamethonium and mivacurium. The inhibition of acetylcholinesterase causes dysfunction at the neuromuscular junction which can produce altered responses to nondepolarising neuromuscular blockers. Anaesthetists may encounter patients exposed to organophosphorus compounds either following acute poisoning, trauma (warfare) or as patients with a wide range of nonspecific disorders presenting for surgery. The traditional use of oximes and atropine in treatment has failed to reduce the morbidity and mortality associated with poisoning. The roles of agents that have reduced the toxicity of organophosphorus compounds in animal experiments are discussed as potential therapeutic agents. There is an urgent need for accurate information on the problems associated with exposure to organophosphorus compounds. This would best be achieved by collaborative research between technologically advanced countries and developing countries, where organophosphorus compounds are a leading cause of ill health.

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Section: Biochemistrymentioning

confidence: 99%

Organophosphorus poisoning and anaesthesia

1999

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“…Those methods include monitoring decreases in blood cholinesterase levels,[ 21 residual nerve agent in blood, 1 31 hydrolysis products of the nerve agent, 1 4-6 1 fluoride reactivated species, [7][8][9] and agent adducts of proteins. [' 01 Because the fluoride reactivation process has been shown to be specific, quantitative, retrospective and relatively simple for the analysis of satin exposures, t7 , 8 1 we have evaluated the application of that process to the analysis of soman and satin exposures with guinea pigs (Cava porcellus) and rhesus monkeys (Macaca mulatta) (hereafter referred to as non-human primates, NHP).…”

Section: Introductionmentioning

confidence: 99%

The Application of the Fluoride Reactivation Process to the Detection of Sarin and Soman Nerve Agent Exposures in Biological Samples

Adams¹,

Capacio²,

Smith³

et al. 2004

Drug and Chemical Toxicology

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information The fluoride reactivation process was evaluated for measuring the level of sarin or soman nerve agents reactivated from substrates in plasma and tissue from in vivo exposed guinea pigs (Cava porcellus), in blood from in vivo exposed rhesus monkeys (Macaca mulatta), and in spiked human plasma and purified human albumin. Guinea pig exposures ranged from 0.05 to 44 LD5 0 , and reactivated nerve agent levels ranged from 1.0 ng/mL in plasma obtained from 0.05 LD 50 sarinexposed guinea pigs to an average of 147 ng/g in kidney tissue obtained from two 2.0 LD 50 soman-exposed guinea pigs. Positive dose-response relationships were observed in all low-level, 0.05 to 0.4 LD 50 , exposure studies. An average value of 2.4 ng/mL for reactivated soman was determined in plasma obtained from two rhesus monkeys three days after a 2 LD 50 exposure. Of the five types of guinea pig

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“…In case of makeshift devices, a larger fraction of agent will be in the spills and a smaller part will usually order of magnitude higher than from vapors. Spills will occur mainly around the point of be aerosolized [51].…”

Section: Skin and Mucous Membranesmentioning

confidence: 99%

“…Biological weapons can enter the digestive system in contaminated food or drinking water, by hand-mouth contact after touching contaminated surfaces, or by swallowing of respiratory mucus after an accumulation of larger aerosol particles in the nose/throat and upper airways. Of all exposure routes this is the easiest to control, provided that the contaminated sources are known [51].…”

Section: Digestive Systemmentioning

confidence: 99%