Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chlorpyrifos (CPS; O,O-diethyl 3,5,6-trichloro-2-pyridyl phosphorothionate; Dursban) is a widely used broad-spectrum organophosphorus (OP) insecticide. Because some OP compounds can cause a sensory-motor distal axonopathy called OP compound-induced delayed neurotoxicity (OPIDN), CPS has been evaluated for this paralytic effect. Early studies of the neurotoxicity of CPS in young and adult hens reported reversible leg weakness but failed to detect OPIDN. More recently, a human case of mild OPIDN was reported to result from ingestion of a massive dose (about 300 mg/kg) in a suicide attempt. Subsequent experiments in adult hens (the currently accepted animal model of choice for studies of OPIDN) showed that doses of CPS in excess of the LD50 in atropine-treated animals inhibited brain neurotoxic esterase (NTE) and produced mild to moderate ataxia. Considering the extensive use of CPS and its demonstrated potential for causing OPIDN at supralethal doses, additional data are needed to enable quantitative estimates to be made of the neuropathic risk of this compound. Previous work has shown that the ability of OP insecticides to cause acute cholinergic toxicity versus OPIDN can be predicted from their relative tendency to inhibit the intended target, acetylcholinesterase (AChE), versus the putative neuropathic target, NTE, in brain tissue. The present study was designed to clarify the magnitude of neuropathic risk associated with CPS exposures by measuring hen brain AChE and NTE inhibition following dosing in vivo and determining the bimolecular rate constant of inhibition (ki) for each enzyme by the active metabolite, CPS oxon (CPO), in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of hen brain acetylcholinesterase and neurotoxic esterase by chlorpyrifos in vivo and kinetics of inhibition by chlorpyrifos oxon in vitro: application to assessment of neuropathic risk. 768 90

Ten common marmosets (Callithrix jacchus) and 10 black-tufted marmosets (Callithrix penicillata) were immobilized to compare the anesthetic effects of racemic ketamine and (S+) ketamine in combination with midazolam. The animals were distributed into four groups: five common marmosets (group CJR) and five black-tufted marmosets (group CPR) received 9.8 +/- 1.4 mg/kg of racemic ketamine, and five common marmosets (group CJS) and five black-tufted marmosets (group CPS) received 10.4 +/- 1.6 mg/kg of (S+) ketamine. All groups received similar dosages of midazolam (1.0 +/- 0.15 mg/kg). During immobilization, heart rates, respiratory rates, rectal temperatures, and muscle relaxation scores were recorded at 5, 10, and 20 min after initial injection. Quality of induction and quality of recovery were evaluated in each marmoset by recording physical reactions including withdrawal reflexes, involuntary movements, salivation, compulsive licking, catalepsy, and ataxia. There were no significant differences in the induction, immobilization, and recovery times between the four groups. Similarly, there were no significant differences between groups in heart rates, respiratory rates, or body temperatures, although there was a significant decrease in respiratory rates over time in group CPR. In addition, the CJR and CPS groups showed significant decreases over time in rectal temperature. Muscle relaxation was more profound in the CPR group than in the other groups. Compulsive licking, involuntary movements, salivation, and withdrawal reflexes were observed more frequently in animals given S(+) ketamine; but in general, racemic ketamine and S(+) ketamine had similar effects in all callitrichines. Further studies are required to confirm that S(+) ketamine has different potency in these species.
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PMID:Comparison of racemic ketamine versus (S+) ketamine when combined with midazolam for anesthesia of Callithrix jacchus and Callithrix penicillata. 2094 34