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)

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

1. Several derivatives and analogues of the general anaesthetic 2,6-diisopropylphenol (propofol) have been recently synthesised with the aim of exploring the structure-activity relationships. 2. In the present study, the effects of one such compound, 4-iodo-2,6-diisopropylphenol (4-I-Pro), on gamma-aminobutyric acid type A (GABA(A)) receptors in vitro were compared with its in vivo effects in rodents. Human GABA(A) receptors were expressed in Xenopus oocytes, and the actions of 4-I-Pro on receptor function were compared with those of propofol by two-electrode voltage-clamp recording. 3. Similar to propofol, 4-I-Pro directly activated Cl- currents in the absence of GABA at all combinations of receptor subunits tested. However, the efficacy of 4-I-Pro in inducing direct activation of alpha1beta2gamma2S receptors was markedly less than that of propofol. 4. Similarly to propofol, 4-I-Pro potentiated in a concentration-dependent manner GABA-evoked Cl- currents measured at different GABA(A) receptor constructs. 5. As expected, intraperitoneal injection of propofol induced sedation, ataxia, and loss of the righting reflex in rats. In contrast, administration of 4-I-Pro failed to produce any of these behavioural effects. 6. Administration of 4-I-Pro to rats reduced in a dose-dependent manner the incidence of tonic-clonic seizures induced by pentylenetetrazol and induced an anticonflict effect as measured in the Vogel test. 7. Microdialysis revealed that, like propofol, administration of 4-I-Pro reduced acetylcholine release in the hippocampus of freely moving rats. 8. These results demonstrate that para-substitution of the phenol ring of propofol with iodine yields a compound that exhibits anticonvulsant and anticonflict effects, but is devoid of sedative-hypnotic and anaesthetic properties. Thus, 4-I-Pro possesses pharmacological characteristics more similar to anxiolytic and anticonvulsant drugs than to general anaesthetics.
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PMID:Characterization of the electrophysiological and pharmacological effects of 4-iodo-2,6-diisopropylphenol, a propofol analogue devoid of sedative-anaesthetic properties. 1021 39

Cresol poisoning was suspected in agroup of cattle presented for slaughter at a federaly inspected plant in Illinois. Four cattle died shortly after being unloaded at the slaughter facility, while another animal died after being returned to the feedlot of origin in Iowa. The clinical signs in the affected cattle were lethargy, depression, ataxia, leg weakness, sternal recumbency, dehydration, and severe bloating. Metacresol (3-methyl phenol), commonly found in disinfectants used to clean and sanitize farm equipment and barns, was detected in rumen content from 4 necropsied animals ranging from 25.3 to 52.6 ppm. The exact source of exposure was not identified, but was probably accidental on the farm of origin or on the trailers used for animal transit to the slaughter plant.
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PMID:Suspected cresol poisoning in cattle presented for slaughter. 1182 64