A5103098243- Pesticide Exposure and Toxicity
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Environmental Toxicology and Ecotoxicology
- Insect and Pesticide Research
- Complementary and Alternative Medicine Studies
- Pesticide and Herbicide Environmental Studies
- Memory and Neural Mechanisms
- Immunotoxicology and immune responses
- Animal testing and alternatives
- Stress Responses and Cortisol
- Metabolomics and Mass Spectrometry Studies
- Disaster Response and Management
- Olfactory and Sensory Function Studies
- Cannabis and Cannabinoid Research
CECOM Software Engineering Center
2017-2018
United States Department of the Army
2014
Summary Objective Exposure to chemical warfare nerve agents ( CWNA s), such as soman GD ), can induce status epilepticus SE ) that becomes refractory benzodiazepines when treatment is delayed, leading increased risk of epileptogenesis, severe neuropathology, and long‐term behavioral cognitive deficits. Rodent models, widely used evaluate novel medical countermeasures MCM s) against exposure, normally express plasma carboxylesterase, an enzyme involved in the metabolism certain...
This article investigated the efficacy of combination antiepileptic drug therapy in protecting against soman-induced seizure severity, epileptogenesis and performance deficits. Adult male rats with implanted telemetry transmitters for continuous recording electroencephalographic (EEG) activity were exposed to soman treated atropine sulfate oxime HI-6 one minute after exposure midazolam, ketamine and/or valproic acid 40 min onset. Rats medical countermeasures evaluated survival, development...
The identification of improved medical countermeasures against exposure to chemical warfare nerve agents (CWNAs), a class organophosphorus compounds, is dependent on the choice animal model used in preclinical studies. CWNAs bind acetylcholinesterase and prevent catalysis acetylcholine, causing plethora peripheral central physiologic manifestations, including seizure. Rodents are widely elucidate effects CWNA-induced seizure, albeit with caveat: they express carboxylesterase activity plasma....
Chemical warfare nerve agent exposure leads to status epilepticus that may progress epileptogenesis and severe brain pathology when benzodiazepine treatment is delayed. We evaluated the dose-response effects of delayed midazolam (MDZ) on toxicity induced by soman (GD) in plasma carboxylesterase knockout (Es1-/- ) mouse, which, similar humans, lacks carboxylesterase. Initially, we compared median lethal dose (LD50 GD female Es1-/- mice across estrous with male observed a greater LD50 during...
The experimental pathophysiology of organophosphorus (OP) chemical exposure has been extensively reported. Here, we describe an altered fecal bacterial biota and urine metabolome following intoxication with soman, a lipophilic G class warfare nerve agent. Nonanesthetized Sprague-Dawley male rats were subcutaneously administered soman at 0.8 (subseizurogenic) or 1.0 (seizurogenic) the 50% lethal dose (LD50) evaluated for signs toxicity. Animals stratified based on seizing activity to evaluate...
The clinical and experimental pathobiology of organophosophate nerve agent exposure has been extensively described. Here, were port for the first time an altered fecal microbiome urine metabolome post‐exposure with soman, a highly lipophilic G‐class agent. Non‐anaesthetized Sprague‐Dawley rats administered soman via sub‐cutaneous injections versus saline control group feces, urine, relevant organs harvested at72 hrs 3 months post‐exposure. To evaluate direct effect on bacterial biota, 16S...
Abstract The experimental pathophysiology of organophosphorus (OP) chemical exposure has been extensively reported. Here, we describe an altered fecal microbiota and urine metabolome that follows intoxication with soman, a lipophilic G class warfare nerve agent. Non-anaesthetized Sprague-Dawley male rats were subcutaneously administered soman at 0.8 - 1.0 the median lethal dose (LD 50 ) evaluated for signs toxicity. Animals stratified based on seizing activity to evaluate effects bacterial...