Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030552 (paresis)
 5,831 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of organophosphorus-induced delayed neurotoxicity (OPIDN) was studied in the European ferret (Mustela putorius furo). A single oral or dermal dose of 250, 500, or 1000 mg tri-o-tolyl phosphate (TOTP)/kg body weight was administered to adult male ferrets. Corn oil served as the vehicle in the oral test and 95% ethanol was the vehicle in the dermal test. At 48 h posttreatment, half the animals in each group were killed by cervical dislocation for assessment of whole-brain neuropathy target esterase (NTE) activity. The remaining 5 animals per group were observed and examined neurologically on a daily basis for a subsequent 54 d. All ferrets dosed dermally with 1000 mg TOTP/kg body weight developed clinical signs characteristic of OPIDN ranging from ataxia to partial paresis. Ferrets administered 250 and 500 mg TOTP/kg body weight via the dermal route displayed variable degrees of hind limb weakness and ataxia. Of the animals dosed orally, only those in the 1000 mg TOTP/kg body weight group showed clinical signs indicative of OPIDN. These signs did not progress beyond mild ataxia. Small amounts of axonal degeneration were noted in the dorsolateral part of the lateral funiculus and in the fasciculus gracilis of spinal cords in ferrets receiving dermal doses of 1000 mg TOTP/kg body weight. Whole-brain neuropathy target esterase activity was also maximally inhibited (46%) in animals receiving 1000 mg TOTP/kg dermally. These results suggest that the ferret is a species that is susceptible to OPIDN.
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PMID:Delayed neurotoxic effects of tri-o-tolyl phosphate in the European ferret. 291 34

A "hen model" or organophosphorus induced delayed neuropathy (OPIDN) has been developed using white leghorn exposed acutely to one of five dosages of tri-ortho-cresyl phosphate (TOCP), between 300 to 700 mg/Kg. Neuropathy target esterase was studied in brain and peripheral nerve 24 and 48 hrs following exposure. Behavioral symptoms abnormality was assessed from days 1 through 20 after exposure using a 7 point rating scale and neuropathological examination was conducted on sample collected from animals on days 0, 7, 14 and 21. Neuropathological abnormalities were indicated by damage scores between 0 (no damage) and 4 (gliosis of brain tissue, myelin loss, appearance of axonal foci etc and more than 55% degeneration of peripheral nerve fibres). TOCP (600 and 700 mg/Kg, orally) was able to inhibit NTE more than 75% in brain and peripheral nerves. TOCP at the same dosage was also capable of resulting maximal levels of neuropathological score at 4. After exposure to doses weight loss was observed abruptly in a greater extent at the beginning leading to a change in weight gain till the end of the experiment. Behavioral signs were also dose dependent. Symptoms (gain abnormality, ataxia, paresis) were noted on the early stage of experiment. Inhibition of NTE was 65% could not be reached in hens given TOCP without causing lethality and no significant ataxia or lesions developed in those birds. Behavioral signs were also observed to be late onset. These data indicate that more than 75% inhibition of peripheral nerve NTE after 24 hr exposure was predictive of severe behavioral abnormalities and pathology in the hen whereas less peripheral NTE inhibition was indicative of less severe behavioral abnormalities and a lower score for neuropathological damage.
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PMID:Biochemical, neuropathological and behavioral studies in hens induced by acute exposure of tri-ortho-cresyl phosphate. 755 52