Definitive Evidence for the Acute Sarin Poisoning Diagnosis in the Tokyo Subway

Nagao, Masataka; Takatori, Takehiko; Matsuda, Yutaka; Nakajima, Makoto; Iwase, Hirotaro; Iwadate, Kimiharu

doi:10.1006/taap.1997.8110

Cited by 214 publications

(114 citation statements)

References 18 publications

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“…However, the prevalence of OPs in the environment has become a public health concern given their toxicity and the number of accidental and intentional poisonings by OPs (e.g., from suicide attempts) (Eddleston et al, 2008). Exposure to OP-based nerve agents from rogue governments and terrorist organizations is an additional risk that was exemplified by the Iraqi military attacks on Kurdish civilians in the 1980s (Macilwain, 1993), the Tokyo sarin attack in 1995 by domestic terrorists (Nagao et al, 1997), and the recent sarin attacks on civilians in Syria (Sellström et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons

Gao

Naughton

Wulff

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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The extensive use of organophosphates (OPs) is an ongoing environmental health concern due to multiple reports of OPrelated neurologic abnormalities. The mechanism of the acute toxicity of OPs has been attributed to inhibition of acetylcholinesterase (AChE), but there is growing evidence that this may not account for all the long-term neurotoxic effects of OPs. In previous experiments (using ex vivo and in vitro model systems) we observed that the insecticide OP chlorpyrifos impaired the movements of vesicles and mitochondria in axons. Here, using a time-lapse imaging technique, we evaluated the OP-nerve agent diisopropylfluorophosphate (DFP) across a wide range of concentrations (subnanomolar to micromolar) for effects on fast axonal transport of membrane-bound organelles (MBOs) that contain the amyloid precursor protein (APP) tagged with the fluorescent marker Dendra2 (APPDendra2). Both 1 and 24 hours of exposure to DFP and a positive control compound, colchicine, resulted in a decrease in the velocity of anterograde and retrograde movements of MBOs and an increase in the number of stationary MBOs. These effects occurred at picomolar (100 pM) to low nanomolar (0.1 nM) concentrations that were not associated with compromised cell viability or cytoskeletal damage. Moreover, the effects of DFP on axonal transport occurred at concentrations that did not inhibit AChE activity, and they were not blocked by cholinergic receptor antagonists. Given the fundamental importance of axonal transport to neuronal function, these observations may explain some of the long-term neurologic deficits that have been observed in humans who have been exposed to OPs.

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Section: Introductionmentioning

confidence: 99%

Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons

Gao

Naughton

Wulff

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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“…Kako sarin hlapi podjednakom brzinom kao i voda, a dnevna temperatura zraka je taj dan bila relativno visoka, veoma je brzo došao u atmosferu. To je klasičan primjer terorističke primjene bojnog otrova iz kućne radinosti koji je imao za posljedicu 5500 otrovanih od kojih je 11 umrlo (71)(72)(73).…”

Section: Biološke Nokseunclassified

Toxicological Effects of Weapons of Mass Destruction and Noxious Agents in Modern Warfare and Terorrism

Vučemilović¹

2010

Archives of Industrial Hygiene and Toxicology

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Oružja za masovno uništavanje najbolji su primjer uporabe civilizacijskih tehnoloških dostignuća u štetne svrhe i protiv ljudske civilizacije. Unatoč nastojanjima oko kontrole i smanjenja njihove količine, rizik zbog samoga postojanja pa čak i širenja zahtijeva da se o njihovoj uporabi i dalje vodi računa i da se povećaju obrambene mjere -nuklearno-biološko-kemijske obrane (NBKO). Osim suvremenog vojnika koji je u vojnim i mirovnim operacijama diljem svijeta izložen raznim noksama kemijskog, biološkog i radiološkog podrijetla, nezaštićeno i uglavnom slabo educirano civilno stanovništvo može biti izloženo terorističkim napadima. Oružja za masovno uništavanje i nokse kemijskog, biološkog i radiološkog podrijetla uzrokuju razne toksikološke posljedice, a bez obzira na njihovo podrijetlo, imaju zajednički nazivnik djelovanja -poremećaj fi ziološkog stanja u organizmu. Poremećaji proizašli nakon izlaganja tim noksama nerijetko se teško determiniraju, dijagnosticiraju i liječe. U ovome su radu s biomedicinskog aspekta obrađene važnije nokse kemijskog, biološkog i radiološkog podrijetla na temelju odabranih primjera iz terorizma i suvremenog ratovanja: polonij-210, osiromašeni uran, salmonela, bedrenica (antraks), genetički modifi cirane bakterije, polimerno predivo "paučina" i bojni otrovi sarin i iperit. Arh Hig Rada Toksikol 2010;61:247-256 Unatoč nastojanjima oko kontrole i smanjenja količine oružja za masovno uništavanje, rizik zbog njegova daljnjeg postojanja pa čak i širenja zahtijeva da se o njegovoj uporabi i dalje vodi računa te da se povećaju obrambene mjere -nuklearno-biološko-kemijske obrane (NBKO) (1-4). KLJUČNE RIJEČI: bedrenica, bojni otrovi, genetski modifi cirane bakterije, iperit, nuklearno-biološko-kemijska obrana, osiromašeni uran, polimerno predivo "paučina", polonij-210, salmonela, sarin, vojne operacije Vučemilović A. NOXIOUS AGENTS IN MODERN WARFARE AND TERORRISMOružja za masovno uništavanje prisutna su kroz cijelu povijest ljudske civilizacije. Od prastarih vremena kada su se protivnicima bacala trupla u bunare s pitkom vodom, do početka 20. stoljeća uglavnom su se rabila različita priručna sredstva u svrhu trovanja ili izazivanja zaraze. Razvoj oružja za masovno uništavanje u današnjem obliku i ustrojstvu počinje tek u 20. stoljeću usporedo s naglim razvojem kemije, biologije i fi zike (5-9).Danas postoji oko 45.000 tona kemijskog oružja deklariranog od Organizacije za zabranu kemijskog oružja (OPCW) za neškodljivo uništenje (10), a velik su ekološki problem i stotine tisuća tona kemijskog streljiva na dnu mora i oceana koje korodira, a izbacivano je s brodova ponajviše nakon II. svjetskog rata (11).Osim oružja za masovno uništavanje, opasnost su i ostale nokse: biološki agensi, kemijski elementi Unauthenticated Download Date | 5/11/18 8:31 AM

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“…Polhuijs et al 14) have verified sarin exposure by detecting sarin in blood samples from victims of the Matsumoto sarin gas attack, using GC-MS through regeneration of sarin from isopropylmethylphosphonylated BuChE with excess fluoride ion. Nagao et al 15) have also verified sarin exposure by detecting isopropylmethylphosphonic acid (IMPA) in blood samples from victims of the Tokyo subway sarin gas attack, using GC-MS through immunoaffinity purification of erythrocyte AChE adducts and IMPA liberation by phosphatase. These two methods using GC-MS are indirect methods for demonstrating CWA exposure.…”

Section: Indirect Analysismentioning

confidence: 99%

Mass Spectrometric Identification of Chemical Warfare Agent Adducts with Biological Macromolecule for Verification of Their Exposure

Tsuge

Seto

2009

JOURNAL OF HEALTH SCIENCE

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Exposure to chemical warfare agents (CWAs) can be verified by detecting their degradation products in biological samples. However, the half-lives of these CWA degradation products in the body are short. CWAs are known to combine with biological macromolecules and the covalently bound compounds are called adducts. The residence time of adducts in the human body is longer than that of the corresponding CWA degradation products. Therefore, development of analytical methods to detect these adducts is a more realistic way of verifying CWA exposure. In this mini review, we describe the present state of research on analytical methods for identifying CWA adducts, and mainly introduce our research on nerve gas adducts using a direct method. Novel analytical methods for verifying low level exposure to nerve gases use liquid chromatography-mass spectrometry (LC-MS). Butyrylcholinesterase (BuChE) has been purified by affinity chromatography and sodium dodecylsulfate poly-acrylamide gel electrophoresis. The purified enzyme is inhibited by nerve gases (sarin, VX and soman) and digested by chymotrypsin, and then the peptides are analyzed by LC-MS and LC tandem MS. The peptide fragment that is combined with nerve gas is detected by LC-MS. Furthermore, the chemical structure of the adduct peptide characterized by MS provides structural information about the analyte. The detection limit of BuChE or BuChE adduct is estimated at 4 ng/injection (53 fmol/injection). If at least 1% of BuChE activity is inhibited by nerve gas, the adduct can be detected at a level of 1% BuChE inhibition in the victim's serum.

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Definitive Evidence for the Acute Sarin Poisoning Diagnosis in the Tokyo Subway

Cited by 214 publications

References 18 publications

Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons

Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons

Toxicological Effects of Weapons of Mass Destruction and Noxious Agents in Modern Warfare and Terorrism

Mass Spectrometric Identification of Chemical Warfare Agent Adducts with Biological Macromolecule for Verification of Their Exposure

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