Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.5 (neuropathy target esterase)
 1,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of a supralethal dose of chlorpyrifos to produce delayed neuropathy was examined using assessments of clinical signs, electromyography (EMG), motor nerve conduction velocity (MNCV), lymphocyte neuropathy target esterase activity (LNTE), and histologic changes in nervous system tissues. Cats were exposed to a single, im injection of corn oil (vehicle control), DFP (positive control) at 5.0 mg/kg, or chlorpyrifos at 300 mg/kg and observed for 60 days. Atropine and 2-PAM were administered to chlorpyrifos exposed cats one to two times a day for 14 to 24 days in response to the appearance of cholinergic signs. Anorectic cats during the acute toxicosis were force fed by hand and hydration was maintained by administering fluids sc. Onset of ataxia (mean +/- SD) for the positive control and chlorpyrifos exposed cats were 16.2 +/- 1.8 days (range of 14-19 days) and 19.0 +/- 1.4 days (range of 17-21 days), respectively. Functional deficits for both groups were confined to the hindlimbs and characterized by a crouched-waddling gait, hypermetria, and proprioceptive deficits. Maximal inhibition of LNTE activity was 96% at 24 hr postdosing in the positive control group and 46% at 7 days postdosing in the chlorpyrifos group. No EMG or MNCV abnormalities were detected in any of the treatment groups. Axonal degeneration was similar for the positive control and chlorpyrifos exposed cats. Ascending tracts of the cervical spinal cord and descending tracts of the thoracic and lumbar spinal cord were most severely affected and peripheral nerves were only mildly affected. The clinical and histologic effects produced indicate that chlorpyrifos can cause delayed neuropathy in the domestic cat. The moderate but prolonged inhibition of LNTE produced by chlorpyrifos is atypical of classic organophosphorus delayed neurotoxicants.
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PMID:Clinical, biochemical, electrophysiologic, and histologic assessment of chlorpyrifos induced delayed neuropathy in the cat. 128 30

This study was aimed to investigate the possibility of modifying the rate of aging of diisopropylfluorophosphate-inhibited neuropathy target esterase (NTE) of hen brain. This reaction on NTE occurs with a half-time of 7.4 min. Atropine was effective in decreasing the rate of aging on DFP-inhibited NTE and this effect was time- and concentration-dependent. Atropine was also a weak but progressive inhibitor of NTE activity (I50 = 80 mM) and this reaction appears to be reversible at lower atropine concentrations. Among compounds containing oxime functional groups only OPAB, having longer methylene chain and being more lipophylic than other oximes usually used in acetylcholinesterase (AChE) reactivation studies, was effective in decreasing the rate of aging on DFP-inhibited NTE. However, when atropine and oximes were used together we have obtained a potentiating and/or synergistic effect which was most significant with combination of atropine and TMB-4 giving up to a 15-fold decrease in the rate of aging reaction. The efficacy of this particular combination was concentration-dependent. We have also discussed similarities and differences in aging reaction occurring on NTE and AChE.
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PMID:Modification of the rate of aging of diisopropylfluorophosphate-inhibited neuropathy target esterase of hen brain. 963 12

Organophosphorus insecticide poisoning is a major global health problem with approximately 3 million poisonings and 200,000 deaths annually. These irreversible inhibitors of acetylcholinesterase produce a well established triphasic effect in man. The initial cholinergic phase due to accumulation of acetylcholine at muscarinic, nicotinic, and central nervous system synapses is a medical emergency that often requires treatment in an intensive care unit. The intermediate syndrome sets in 2-4 days after initial exposure, due to pre-and postsynaptic dysfunction at the neuromuscular junction, and causes respiratory failure for which ventilatory care is necessary. The delayed polyneuropathy sets in about 21 days after exposure, due to phosphorylation of neuropathy target esterase, and produces symmetrical motor weakness of peripheral muscles with a variable sensory component. The organophosphorus compounds are known to produce effects on the nervous, cardiovascular, and reproductive systems in man and animals, producing a wide range of effects. Further interference with temperature regulation, metabolic and endocrine function along with disturbances in vision, affection of vocal cords, and immunity could present challenging medical scenarios for a clinician. Biochemical assays of cholinesterase and organophosphorus agents have undergone considerable review, and progress is being made to develop scientifically reliable criteria for diagnosis and management. Atropine and pralidoximes have been the major therapeutic agents for intoxication, but the unacceptable mortality and morbidity associated with poisoning necessitates change and the use of agents like clonidine and fluoride, which have potentially beneficial effects. There is need for collaborative research and study between the technologically developed countries and the third-world countries, where the vast majority of health disorders associated with organophosphorus insecticides is encountered.
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PMID:Organophosphorus Insecticide Poisoning. 3072 Feb 57