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

Cyanofenphos (surecide)(R), 25% E.C., O-ethyl O-(4-cyanophenyl) phenylphosphonothioate, was orally administered to one year old lambs at sublethal doses of 1 mg, 2 mg and 4 mg active ingredient kg-1 day-1 for time intervals 60, 45 and 30 days respectively. Irreversible paralytic ataxia symptoms of delayed neuropathy appeared at about 80, 50 and 30 days respectively. In weekly blood samples, AChE (acetylcholine-sterase) and MAO (monoamine oxidase) activities were inhibited depending upon level of dosing and time interval. However no significant correlation was found between the extent of plasma AChE and MAO inhibition and the onset of ataxia symptoms. In brain samples from ataxiated animals, AChE, MAO and NTE (neurotoxic esterase) activities were assayed simultaneously with untreated animal. Direct correlation was shown between in vivo NTE inhibition and the occurrence of delayed neuropathy. Cyanofenphos is the third compound of the phenyl phosphonothioate type on the market showing delayed neuropathy together with Leptophos and EPN.
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PMID:Delayed neuropathy in sheep by the phosphonothioate insecticide cyanofenphos. 43 64

Organophosphate-induced delayed polyneuropathy (OPIDP) is thought to result from organophosphorylation of neuropathy target esterase (NTE), followed by an "aging" of the phosphorylated NTE. Prophylactic against OPIDP should thus be achieved by production of an inhibited but "nonaging" NTE. Resolved stereoisomers of ethyl phenylphosphonic acid esters produce two forms of inhibited NTE; in vitro one form ages rapidly and the other only negligibly. The present study examined the in vivo effects of two preparations of incompletely resolved isomers of EPN oxon (ethyl 4-nitrophenyl phenylphosphonate) and its thionate on adult hen brain and spinal cord NTE and the relationship of inhibition and aging to the development of OPIDP. Single doses of the L-(-)-isomers (Preparation A, 7:3 proportion of isomers, or Preparation B, 9:1) caused severe neuropathy after doses which produced 70% aged inhibited NTE and mild effects after 50-60%. Single doses of the D-(+)-isomers produced either equal amounts of aged and unaged inhibited NTE (Preparation A) or predominantly unaged (Preparation B): the amount of aged was never more than 50% and no clinical OPIDP occurred. Doses of D-(+) which produced 50% unaged inhibited NTE were protective: challenge with the highly neuropathic phenyl saligenin cyclic phosphate did not cause OPIDP. All effects are consistent with the two-stage initiation process which requires both inhibition of NTE and subsequent modification of the protein by an "aging" process. Previously reported neuropathic effects of D-(+)-EPN probably reflect a substantial proportion of L-(-)-isomer present in the test material. Neuropathic studies with chiral OP esters should consider the possibility of production of protective unaged inhibited NTE in test animals.
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PMID:The influence of chirality on the delayed neuropathic potential of some organophosphorus esters: neuropathic and prophylactic effects of stereoisomeric esters of ethyl phenylphosphonic acid (EPN oxon and EPN) correlate with quantities of aged and unaged neuropathy target esterase in vivo. 362 85

Organophosphate-induced delayed polyneuropathy (OPIDP) has been tested mainly byin vivo methods in the chicken and by examination of the inhibition of neuropathy target esterase in their neuronal tissue. An alternative method, using permanent neuronal cell lines and detecting the growth of neurite-like sprouts by morphometric means, has meanwhile been validated to substitute thesein vivo investigations, at least in part. This paper reports some modifications of this in vitro method in order to optimize it for a routine laboratory screening test of organophosphates. By determination of cytoskeletal elements with cell ELISA, it was demonstrated that seven OPIDP-inducing compounds [tri-o-cresyl phosphate (TOCP) and its metabolite cresyl-saligeninphosphate, haloxon, mipafox, leptophos, EPN and chlorpyrifos] and nine negative control substances [paraoxon, methylazinphos, ethylazinphos, dimefox, dimethoate, phenylmethanesulfonylfluoride (PMSF) and three organophosphate metabolite-cresol, phenol and p-nitrophenol] resulted in the same effects as seen in the original test method. The cell ELISA technique thus represents an alternative method that is much easier to perform than the morphometric method.
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PMID:Improved in vitro method for screening organophosphate-induced delayed polyneuropathy. 2065 12