A murine model for sarin exposure using the carboxylesterase inhibitor CBDP

Garrett, Teresa L.; Rapp, Christine M.; Grubbs, Robert D.; Schlager, John J.; Lucot, James B.

doi:10.1016/j.neuro.2010.05.007

Cited by 14 publications

(5 citation statements)

References 36 publications

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“…Animal models are important in the understanding of some of the neurotoxic effects that may be experienced short‐ and long‐term in humans . The long‐term effects of OP exposure first seen after the Tokyo attack arose from non‐AChE inhibition, because OPs have secondary targets . Glutamate is an excitatory neurotransmitter in the brain responsible for critical functions such as cognition, memory, and learning .…”

Section: Discussionmentioning

confidence: 99%

A Comparative Toxidrome Analysis of Human Organophosphate and Nerve Agent Poisonings Using Social Media

Reddy

Colman

2017

Clinical Translational Sci

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Here we utilized social media to compare the toxidrome of three lethal chemical exposures worldwide. YouTube videos were the main source from which the data were collected, but published reports and news were also utilized to fill in some gaps. All videos were organized in a database detailing symptoms and severity of each victim, along with demographics such as approximate age and gender. Each symptom was rated as mild, moderate, or severe and corresponding pie graphs for each incident were compared. The videos displayed symptoms ranging from mild to severe cholinergic toxicity and life‐threatening convulsions. Social media may represent an important resource in developing a viable approach to the early detection and identification of chemical exposure, reinforce our preparedness for better antidotes, long‐term follow up, and training about deadly chemical nerve agent attacks.

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Section: Discussionmentioning

confidence: 99%

A Comparative Toxidrome Analysis of Human Organophosphate and Nerve Agent Poisonings Using Social Media

Reddy

Colman

2017

Clinical Translational Sci

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“…A functional observational battery (FOB) was performed using the method of Garrett et al [7] to determine the severity of poisoning, including seizure activity. Animals were observed every 15 minutes for an hour post-injection.…”

Section: Functional Observational Batterymentioning

confidence: 99%

A Comparison of the Sensitivityof Different Strains of Mice to Sarin

Furman¹,

Garrett²,

Rapp³

et al. 2014

Mil. Med. Sci. Lett.

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Poisoning from chemical warfare agents (CWAs) such as sarin is associated with neuronal degeneration. This damage is thought to result from glutamatergic excitotoxicity such as seen following kainic acid induced seizures. In order to search for novel neuroprotectants it is necessary to select good mouse models for susceptibility to nerve agent-induced seizures and the resulting neurodegeneration. The mouse strains tested (C57BL/6, ICR, DBA/2, SW, and FVB/N, Harlan Laboratory) had widely different sensitivity to sarin as shown by differences in the dose required resulting in 50% mortality, LD 50. Differences also were observed among the strains in Fluoro-Jade C staining with the C57BL/6 and DBA having little to no staining when euthanized at 7 days whereas the other strains did. Differences in acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity were found among the strains as well. The ICR strain was excluded from the FOB and weight data due to difficulty getting a consistent LD 50. Weight loss and FOB scores were similar for all strains. All strains had inhibited AChE activity after sarin exposure and exhibited inhibition of CNS BuChE after sarin exposure but only ICR and SW reached significance.

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“…Toxicity of nerve agents has been shown in multiple animal species including mice, guinea pigs, non‐human primates, and minipigs using various routes of exposures and the therapeutic mode of action of HuBChE in guinea pigs and non‐human primates is very similar with respect to the mechanism of action of how HuBChE provides protection against nerve agent toxicity observed in humans. While numerous studies have been conducted in rodents, it has been documented that rodents may not be an acceptable animal model for studying antidotes to nerve agent toxicity since these species have high levels of carboxylesterase, an enzyme that naturally eliminates OP nerve agents from the bloodstream . There are differences in the carboxylesterase concentration in the serum of different mammalian species and those differences are responsible for altering the toxicokinetics of GD, resulting in the reported differences in the LD 50 of this highly toxic material in rat versus guinea pig or rhesus monkeys .…”

Section: Introductionmentioning

confidence: 99%

Human butyrylcholinesterase efficacy against nerve agent exposure

Reed

Sabourin

Lenz³

2017

J Biochem & Molecular Tox

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Acetylcholinesterase is vital for normal operation of many processes in the body. Following exposure to organophosphorus (OP) nerve agents, death can ensue without immediate medical intervention. Current therapies mitigate the cholinergic crisis caused by nerve agents but do not fully prevent long-term health concerns, for example, brain damage following seizures. Human butyrylcholinesterase (HuBChE) is a stoichiometric bioscavenger being investigated as an antidote for OP nerve agent poisoning. HuBChE sequesters OP nerve agent in the bloodstream preventing the nerve agent from reaching critical target organ systems. HuBChE was effective when used as both a pre-treatment and as a post-exposure therapy. HuBChE has potential for use in both military settings and to protect civilian first responders in situations where nerve agent usage is suspected. We reviewed various animal models studies evaluating the efficacy of HuBChE against nerve agent exposure, pursuant to its submission for approval under the FDA Animal Rule.

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A murine model for sarin exposure using the carboxylesterase inhibitor CBDP

Cited by 14 publications

References 36 publications

A Comparative Toxidrome Analysis of Human Organophosphate and Nerve Agent Poisonings Using Social Media

A Comparative Toxidrome Analysis of Human Organophosphate and Nerve Agent Poisonings Using Social Media

A Comparison of the Sensitivityof Different Strains of Mice to Sarin

Human butyrylcholinesterase efficacy against nerve agent exposure

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