The effects and treatment of nerve gas poisoning

Grob, David; Harvey, A. M.

doi:10.1016/0002-9343(53)90358-1

Cited by 147 publications

(61 citation statements)

References 5 publications

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“…Although the volunteers did not develop overt signs of acute toxicity, they presented with a syndrome that was broadly referred to as a "state of altered awareness" and was characterized by difficulty in sustaining attention and slowing of intellectual and motor processes, in addition to subjective feelings of agitation, anxiety, and confusion (Bowers et al, 1964). In general, these clinical manifestations were associated with the inhibition of AChE in red blood cells, and symptomatic recovery was associated with the recovery of AChE activity (Grob and Harvey, 1953;Bowers et al, 1964). Long-term follow-up of these individuals is not available.…”

Section: Clinical Manifestations Of Human Exposure To Op Compounds: Amentioning

confidence: 99%

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

Pereira

Aracava

DeTolla

et al. 2014

J Pharmacol Exp Ther

104

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The translational capacity of data generated in preclinical toxicological studies is contingent upon several factors, including the appropriateness of the animal model. The primary objectives of this article are: 1) to analyze the natural history of acute and delayed signs and symptoms that develop following an acute exposure of humans to organophosphorus (OP) compounds, with an emphasis on nerve agents; 2) to identify animal models of the clinical manifestations of human exposure to OPs; and 3) to review the mechanisms that contribute to the immediate and delayed OP neurotoxicity. As discussed in this study, clinical manifestations of an acute exposure of humans to OP compounds can be faithfully reproduced in rodents and nonhuman primates. These manifestations include an acute cholinergic crisis in addition to signs of neurotoxicity that develop long after the OP exposure, particularly chronic neurologic deficits consisting of anxiety-related behavior and cognitive deficits, structural brain damage, and increased slow electroencephalographic frequencies. Because guinea pigs and nonhuman primates, like humans, have low levels of circulating carboxylesterases-the enzymes that metabolize and inactivate OP compounds-they stand out as appropriate animal models for studies of OP intoxication. These are critical points for the development of safe and effective therapeutic interventions against OP poisoning because approval of such therapies by the Food and Drug Administration is likely to rely on the Animal Efficacy Rule, which allows exclusive use of animal data as evidence of the effectiveness of a drug against pathologic conditions that cannot be ethically or feasibly tested in humans.

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Section: Clinical Manifestations Of Human Exposure To Op Compounds: Amentioning

confidence: 99%

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

Pereira

Aracava

DeTolla

et al. 2014

J Pharmacol Exp Ther

104

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“…Parathion, bis-(monoisopropylamino)-fluorophosphine oxide (Mipafox®), hexaethyl tetraphosphate (HETP), and TEPP have been widely used as agricultural insecticides, and their indiscriminate dispersal has resulted in a number of instances of poisoning, some of them fatal (8)(9)(10). The nerve gases are related compounds which, because of their high toxicity and physical properties, are among the most potent chemical warfare agents (11)(12)(13)(14). One of the most important of these is sarin (isopropyl methyl phosphonofluoridate) (15), which has also been designated GB, and has the structural formula:…”

mentioning

confidence: 99%

Effects in Man of the Anticholinesterase Compound Sarin (Isopropyl Methyl Phosphonofluoridate)1

Grob¹,

Harvey²

1958

J. Clin. Invest.

Self Cite

178

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“…Nerve agents bind covalently to the enzyme acetylcholinesterase (AChE), irreversibly inhibiting it and causing accumulation of acetylcholine (ACh) at neuroeffector junctions in the peripheral and central nervous systems (14,79,81). Similarly, nerve agents inhibit the blood cholinesterases (ChEs), but these are not the targets of toxicity and are of unknown function (13).…”

Section: Ch2-ch2-ci S Ch2-ch2-cimentioning

confidence: 99%

Hazards of chemical weapons release during war: new perspectives.

Reutter

1999

Environ Health Perspect

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The two major threat classes of chemical weapons are mustard gas and the nerve agents, and this has not changed in over 50 years. Both types are commonly called gases, but they are actually liquids that are not re ly voatile. These agents were designed specifically to harm people by any route of exposure and to be effective at low doses. Mustard gas was used in World War I, and the nerve agents were developed shortly before, during, and after World War II. Our perception of the potency of chemical weapons has changed, as well as our concern over potential effects of prolonged exposures to low doses and potential target populations that indude women and cildren. Many of the toxicologic studies and human toxicity esmates for both mustard and nerve agents were designed for the purpose of quickly developing maximal casualties in the least sensitive male soldier. The 'toxcity" of the chemical weapons has not changed, but our perception of 'toxicity" has.

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The effects and treatment of nerve gas poisoning

Cited by 147 publications

References 5 publications

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

Effects in Man of the Anticholinesterase Compound Sarin (Isopropyl Methyl Phosphonofluoridate)1

Hazards of chemical weapons release during war: new perspectives.

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