Ruthie H. Ratcliffe

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Utilizing our previously reported in silico pharmacophore model for reactivation efficacy of oximes, we present here a discovery of twelve new non-oxime reactivators of diisopropylfluorophosphate (DFP)-inhibited acetylcholinesterase (AChE) obtained through virtual screening of an in-house compound database. Rate constant (kr) efficacy values of the(More)
A rapid and sensitive assay for pyridinium oximes in plasma and tissue was developed. The method was suitable for the analysis of mono- and di-pyridinium oximes and utilizes ultrafiltration followed by cation-exchange high-performance liquid chromatography with UV detection. The assay was originally developed for the measurement of the oxime MMB-4 in plasma(More)
The toxicity of organophosphorous (OP) nerve agents is attributed to their irreversible inhibition of acetylcholinesterase (AChE), which leads to excessive accumulation of acetylcholine (ACh) and is followed by the release of excitatory amino acids (EAA). EAAs sustain seizure activity and induce neuropathology due to over-stimulation of N-methyl-d-aspartate(More)
We developed a rat pilocarpine seizure/status epilepticus (SE) model, which closely resembles 1.6-2.0 x LD50 soman exposure, to analyse the molecular mechanism of neuronal damage and to screen effective neuroprotectants against cholinergic agonist and chemical warfare nerve agent (CWNA) exposure. Rats implanted with radiotelemetry probes capable of(More)
Novel therapeutics to overcome the toxic effects of organophosphorus (OP) chemical agents are needed due to the documented use of OPs in warfare (e.g. 1980-1988 Iran/Iraq war) and terrorism (e.g. 1995 Tokyo subway attacks). Standard OP exposure therapy in the United States consists of atropine sulfate (to block muscarinic receptors), the(More)
A novel approach to broad-specificity medical countermeasure against chemical warfare nerve agent (CWNA) poisoning is by preventing excessive accumulation of ACh attributable to AChE inhibition of CWNA exposure. The effectiveness of various partial adenosine A1 receptor agonists as post-CWNA exposure (1 hour) neuroprotectants was investigated in the study(More)
Sulfur mustard is a chemical warfare agent and potent vesicant that penetrates rapidly through the skin and causes prolonged injuries and incapacitation. Severe exposure to HD induces blistering skin reactions and significant loss of stem cell keratinocytes that are required for a continuous renewal of the epidermal cell layer. Therefore, HD injuries(More)
Due to the documented use of organophosphorus (OP) chemical agents in warfare and by terrorists around the globe, Federal, State, and local authorities need novel therapeutics to overcome their deleterious effects. OPs inhibit cholinesterases (ChE), leading to accumulation of the neurotransmitter acetylcholine (ACh). Potentially lethal effects begin with(More)
Objectives To investigate the effects of caffeine on psychomotor vigilance and sleepiness during sleep restriction and following subsequent recovery sleep. Methods Participants were N=48 healthy good sleepers. All participants underwent 5 nights of sleep satiation [time-in-bed (TIB): 10 hrs], followed by 5 nights of sleep restriction (TIB: 5 hrs), and 3(More)
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