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)

Mipafox administered to rats daily for 35 days produced ataxia and a reduction in the level of dopamine in the corpus striatum. Treatment with Leptophos for the same period produced slight motor dysfunction and a small but significant reduction in the level of striatal dopamine. Fenitrothion neither produced motor dysfunction nor changed the level of striatal dopamine. The cholinesterase activity of corpus striatum was inhibited by all the compounds. The results suggest the possible involvement of striatal dopamine in the delayed neurotoxic effects of certain organophosphorus compounds.
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PMID:Role of striatal dopamine in delayed neurotoxic effects of organophosphorus compounds. 5 73

Organophosphorus compounds which, after acute administration, inhibit neurotoxic esterase (NTE) by greater than or equal to 65% and undergo a subsequent "aging" reaction, produce a delayed neuropathy characterized by degeneration of large and long nerve fibers (OPIDN). The present studies examine in detail the NTE-inhibiting properties of triphenyl phosphite (TPP), a plasticizer which produces ataxia and degeneration of the spinal cord in animals. A neurotoxic dosing regimen (1184 mg/kg/week, sc, for 2 weeks) inhibited both brain and spinal cord NTE (less than or equal to 40%) only marginally 4 and 48 hr postdosing. By contrast, TPP was shown in vitro to be a potent (150 = 0.98 microM) inhibitor of rat brain NTE relative to Mipafox or diisopropyl phosphorofluoridate. Compounds structurally related to TPP (i.e., triphenyl phosphate, triphenyl phosphine, trimethyl phosphite, and phenol) failed to inhibit NTE in vitro at less than 10 microM concentrations. Close examination of the TPP inhibition of NTE showed a nonlinear relationship between the duration of incubation time and loss of log(NTE activity). Preincubation of 10 microM TPP in buffer (37 degrees C) resulted in a time-dependent loss of TPP's ability to inhibit NTE. In summary, TPP is a powerful NTE inhibitor in vitro, but only a marginal NTE inhibitor after in vivo administration. These results raise questions as to the causal events mediating TPP-induced neuropathy in the rat.
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PMID:Triphenyl phosphite: in vivo and in vitro inhibition of rat neurotoxic esterase. 382 83

A case of 38 year old man who worked with organochlorinated and Parathion during 5 years is reported. His follow-up was up to 2 years. The onset of the disease was characterized by cholinergic signs, headache, loss of weight, trembling, miokimias, fasciculations, ataxia, myotonic phenomena (in hands only) and motor sensitive peripheral polyneuropathy (affecting the lower limbs symmetrically). Low concentrations of blood cholinesterases confirmed the etiology. Myotonic phenomena disappeared spontaneously 6 months after the initial observation. One year later, the concentration of erythrocyte acetylcholinesterase was found to be low and plasma cholinesterase was normal, suggesting that the patient was carrier of a congenital deficiency of acetylcholinesterase. In literature relationship between myotonia and intoxication due to organophosphorus was not found. The whole clinical picture, cholinergic symptoms, transitory phenomena and spontaneous motor activity could be explained by an excess of acetylcholine. Electromyography (EMG) in the first observation showed neuromuscular transmission blocking characterized by deficiency or absence of voluntary activity, unexcitability of fibular nerves, with fibrillations and positive peaks as described previously with Mipafox (another organophosphorus agent). During 2 years of observation numerous end-plates potentials of muscular fibres persisted in the EMG. A progressive increase in voluntary activity showed by unit motor potential of almost normal amplitude and very increased duration was observed. No potentials of reinnervation were noted. The results of EMG were explained as disturbances of neuromuscular transmission associated with moderate signs of denervation. The Eaton-Lambert's test and the stimulation of a single unit motor potential confirmed disorder of neuromuscular synapses. The histochemistry of brachial biceps showed scattered atrophic and angulated type I and II fibres. Teased-fibres preparations showed nerve fibres with B, C, and G alterations as defined by Dyck et al. indicating axonal degeneration. These results were according to velocity of sensitive conduction. The conduction velocity of fibular nerves was strongly delayed during all the evolution indicating serious disorders of motor nerves myelin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Polyneuropathy caused by parathion: clinical, electrophysiologic and histologic studies of a case]. 665 78

Hens treated with Mipafox (10 mg/kg, sc), sarin (50 micrograms/kg, sc) or parathion (1 mg/kg, sc) daily for 10 days exhibited severe, moderate and no ataxia respectively on 14th day after the start of exposure. The neurotoxic esterase (NTE) activity was significantly inhibited in the brain, spinal cord and platelets of hens treated with mipafox or sarin whereas no change was noticed with parathion treatment. All three compounds significantly inhibited acetylcholinesterase (AChE) activity in the platelets. Spinal cord of hens treated with mipafox, sarin or parathion showed axonal degeneration heavy, moderate and none respectively. It is concluded that repeated administration of equitoxic doses of mipafox, sarin and parathion to hens are marked, moderate and non-delayed neurotoxic respectively.
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PMID:A comparative study of delayed neurotoxicity in hens following repeated administration of organophosphorus compounds. 770 69