Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The signs of neurotoxicity observed in the cat and the rat following single or multiple doses of the phosphorous acid ester triphenyl phosphite (TPP) have been reported to differ from the syndrome known as organophosphorous compound induced delayed neuropathy (OPIDN) caused by some phosphoric acid esters. Since the hen is the test animal traditionally used to test compounds for OPIDN, we chose to study the neurotoxicity of single, subcutaneous doses of TPP using the hen. TPP (1000 mg/kg) produced progressive ataxia and paralysis which developed 5-10 days after dosing. The clinical signs were accompanied by axonal damage in the lateral columns of the spinal cord and peripheral nerve. Similar signs were observed following neurotoxic doses of the OPIDN-causing agents tri-o-cresyl phosphate (TOCP) or diisopropyl phosphorofluoridate (DFP). In addition, TPP caused damage to axons in the brain and gray matter of the spinal cord, and chromatolysis and neuronal necrosis were frequently observed in the spinal cord. These latter areas were not affected by TOCP or DFP. The minimum neurotoxic dose of TPP was found to be 500 mg/kg. Prior administration of phenylmethylsulfonyl fluoride (PMSF) reduced the incidence of damage to the peripheral nerve of animals dosed with TPP, but did not prevent toxic effects on the cell bodies in the spinal cord or the clinical effects. The results of this study indicate that TPP causes neuronal damage in addition to the axonal damage observed with OPIDN. Therefore, we conclude that two distinct mechanisms underlie the neurotoxicity of TPP.
 ...
PMID:Histopathological assessment of triphenyl phosphite neurotoxicity in the hen. 320 32

The neuropathic syndrome resulting in the cat and the rat from single or multiple doses of the phosphorous acid ester tiphenyl phosphite (TPP) has been reported to differ from the syndrome caused by numerous phosphoric acid esters, which is known as organophosphorous compound-induced delayed neurotoxicity (OPIDN). Since the hen is used to test compounds for OPIDN, we chose to study the neurotoxicity of single subcutaneous doses of TPP using this animal model. TPP (1000 mg/kg) produced progressive ataxia and paralysis which began to develop 5-10 days after dosing. Similar signs were observed when subcutaneous doses of the OPIDN-causing agents tri-o-cresyl phosphate (TOCP) or diisopropyl phosphorofluoridate (DFP) were administered. The minimum neurotoxic dose of TPP was 500 mg/kg. Prior administration of phenylmethylsulfonyl fluoride (PMSF) prevented the development of a neuropathy induced by DFP, but did not fully protect the hens from TPP or TOCP. PMSF slowed, but did not prevent, the neuropathy caused by TOCP. PMSF reduced the neurotoxicity of 500 mg/kg TPP, but increased the neurotoxicity of 1000 mg/kg TPP. TPP was found to be a very potent inhibitor of neurotoxic esterase (NTE), the putative target site for OPIDN, in vitro, with a ki of about 2.1 x 10(5) M-1 min-1. Equimolar doses of either TPP (1000 mg/kg) and TOCP (1187 mg/kg) caused over 80% inhibition of neurotoxic esterase (NTE) in brain and sciatic nerve. This high level of NTE inhibition persisted for several weeks. This prolonged inhibition probably accounts for the inability of PMSF to block the neurotoxicity of TOCP.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Triphenyl phosphite neurotoxicity in the hen: inhibition of neurotoxic esterase and of prophylaxis by phenylmethylsulfonyl fluoride. 324 48

Seasonal ataxia was reported in humans following the consumption ofAnaphe venata larva as protein supplement in diet and altered motor function in rodents when the extract was administered intraperitoneally. In this study we investigated the effect of the crude aqueous and Phosphate Buffer Saline (PBS) extracts of this larva on altered spontaneous rat behavior in a novel environment particularly chewing behaviour, with a view to determine the mechanism(s) involved in these behavioural alteration. Animals were randomly assigned into four groups (n = 6-12 per group) and graded doses of aqueous and PBS extracts (100-400 mg/kg) were administered dissolved in saline intraperitoneally (i.p.) to each animal in the experimental groups. The control group received an equivalent volume of saline. Behavioral scores were recorded for a period of 30 minutes after the administration of saline or extract. The role of various receptors in the extract induced chewing was evaluated using known receptor agonist/antagonists. Results revealed a significant increase in purposeless chewing (F (7, 95) = 7.85; p <0.05) by the aqueous extract compared to saline control at all dose levels, which was significantly attenuated by scopolamine (3 mg/kg, i.p) and thiamine (1 mg/kg, i.p) respectively (p <0.05); while flumazenil (2 mg/kg, i.p) and naloxone (2.5 mg/kg, i.p) did not alter the induced purposeless chewing behaviour. Also, administration of PBS induced a significant (F (7, 95) = 6.11; p <0.05) increase in chewing behaviour but only at 400 mg/kg dose level which was attenuated by scopolamine (3 mg/kg, i.p); while flumazenil (2 mg/kg, i.p), naloxone (2.5 mg/kg, i.p), and thiamine (1 mg/kg, i.p) potentiated purposeless chewing behaviour respectively. It may therefore be concluded from this study that Anaphe extract-induced purposeless chewing behaviour in rat is mediated via the activation of cholinergic neurotransmission which is modulated by GABAergic and opioid receptor systems.
 ...
PMID:Anaphe venata larva extract-induced purposeless chewing in rats: the role of cholinergic, GABAergic and opioid systems. 2231 3

Hypophosphatemia (HP) with or without intracellular depletion of inorganic phosphate (Pi) and adenosine triphosphate has been associated with central and peripheral nervous system complications and can be observed in various diseases and conditions related to respiratory alkalosis, alcoholism (alcohol withdrawal), diabetic ketoacidosis, malnutrition, obesity, and parenteral and enteral nutrition. In addition, HP may explain serious muscular, neurological, and haematological disorders and may cause peripheral neuropathy with paresthesias and metabolic encephalopathy, resulting in confusion and seizures. The neuropathy may be improved quickly after proper phosphate replacement. Phosphate depletion has been corrected using potassium-phosphate infusion, a treatment that can restore consciousness. In severe ataxia and tetra paresis, complete recovery can occur after adequate replacement of phosphate. Patients with multiple risk factors, often with a chronic disease and severe HP that contribute to phosphate depletion, are at risk for neurologic alterations. To predict both risk and optimal phosphate replenishment requires assessing the nutritional status and risk for re-feeding hypophosphatemia. The strategy for correcting HP depends on the severity of the underlying disease and the goal for re-establishing a phosphate balance to limit the consequences of phosphate depletion.
...
PMID:Using phosphate supplementation to reverse hypophosphatemia and phosphate depletion in neurological disease and disturbance. 2590 52