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)

Daily oral administration of small doses of technical grade O-methyl O-4-bromo-2,5-dichlorophenyl phenylphosphonothioate (leptophos, 0.5-20.0 mg/kg) caused delayed neurotoxicity in hens. Severity of clinical condition and progression or improvement of signs of delayed neurotoxicity depended on the dose and duration of administration. Hens given 20.0 mg/kg suffered ataxia, paralysis, and death. Intermediate doses (5 and 10 mg/kg) caused ataxia, with most treated hens showing no change in clinical condition during the 4-mo observation period. Hens given small doses (2.5 and 1.0 mg/kg) demonstrated regression of neurological deficits after administration of leptophos was stopped. Hens given the smallest tested dose (,.5 mg/kg) developed mild ataxia and showed total recovery during the observation period. Days of administration and total administered dose before onset of ataxia depended on the daily dose. Degeneration of axons and myelin i, the spinal cord was the most consistent histopathologic change and was identical to that observed in tri-o-cresyl phosphate (TOCP) control hens. Only one hen, which died early in the treatment period, showed peripheral nerve degeneration. Controls consisted of 3 groups of hens given a daily oral dose of 10.0 mg/kg TOCP, 1.0 mg/kg O,O-diethyl O-4-nitrophenyl phosphorothioate (parathion), or an empty gelatin capsule. TOCP-treated hens developed delayed neurotoxicity, whereas those given parathion showed initial leg weakness but subsequently recovery without developing delayed neurotoxicity. Controls given gelatin capsules remained normal.
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PMID:Delayed neurotoxicity of subchronic oral administration of leptophos to hens: recovery during four months after exposure. 9 48

Recent investigation into a possible association between exposure to Leptophos and neurological symptoms in insecticide factory workers makes study of the neurological effects of Leptophos in the experimental situation particularly important. The present study utilizes a single oral dose of 200 mg/kg of Leptophos in 20 chickens which are sacrificed in pairs to define the temporal sequence of changes in the sciatic nerve, its major branches, and the spinal cord and to correlate these findings with the clinical symptoms of the animals. At this dose Leptophos produces degeneration of the spinal cord in a pattern similar to that seen with tri-o-cresyl phosphate (TOCP). The ataxia seen in these birds is probably due to the posterior and lateral column involvement. At this dose onset of paralysis correlates roughly with both the degeneration of the anterior descending tract of the spinal cord and degeneration of the peripheral nerve. The minimal degree of nerve involvement suggests that the cord lesion is more significant at this dose in the hen. Using TOCP, spinal cord lesions predominate in the hen while the peripheral nervous system appears more sensitive in the human and non-human primate. Assuming that Leptophos resembles TOCP in this regard, peripheral nerve damage would be the expected earliest change, especially in the low-dose situation in the human.
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PMID:The neuropathology of leptophos in the hen: a chronologic study. 31 17

Several dimethyl phosphate behave anomalously in tests for delayed neurotoxicity. Doses given to hens caused high inhibition of brain neurotoxic esterase (NTE) but no ataxia. Less inhibition of NTE was seen in spinal cord than in brain. Di-isopropyl phosphorofluoridate caused equal inhibition of NTE in brain and cord. When dosing with dimethyl phosphates was repeated NTE inhibition in cord increased and pair-dosed birds became ataxic. In vitro brain and cord NTE were indistinguishable but the in vivo discrepancy between inhibition of brain and cord NTE was matched by a similar discrepancy in inhibition of AChE. It appears that ataxia arises from inhibition of spinal cord NTE and that only in the present cases (among about 200) was the effect in brain not a perfect biochemical monitor.
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PMID:The anomalous behaviour of dimethyl phosphates in the biochemical test for delayed neurotoxicity. 71 19

Calcium- and calmodulin-regulated protein phosphorylation has been suggested to play a role in the pathogenesis of organophosphorus compound-induced delayed neurotoxicity (OPIDN). This condition is characterized by ataxia that progresses to paralysis concurrent with a central-peripheral distal axonopathy after a delay period of 1-2 weeks following exposure to an organophosphorus compound causing delayed neurotoxicity, such as tri-o-cresyl phosphate (TOCP). Calcium/calmodulin (CaM) kinase II is involved in the increased phosphorylation of brain microtubule and spinal cord neurofilament triplet proteins following treatment of animals with organophosphorus compounds that are capable of producing OPIDN. In this study, chickens were given a single oral neurotoxic dose of 750 mg TOCP/kg body weight and killed after 1, 6, 14 or 21 days following treatment. Protein kinase-mediated phosphorylation of cytoskeletal proteins was studied in proximal and distal parts of sciatic nerves of control and treated hens. Peripheral nerve proteins were phosphorylated in vitro using [gamma-32P]ATP as a phosphoryl group donor. Phosphorylated proteins were separated by one- and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein phosphorylation was detected by autoradiography and quantified by laser microdensitometry. The extent of Ca2+-calmodulin dependent phosphorylation of five cytoskeletal proteins was significantly increased in TOCP treated animals, particularly at 1 and 6 days after treatment, in both the proximal and distal portion of the nerve. The identity of these proteins was confirmed by 2-D PAGE as tubulin, the neurofilament triplet proteins and microtubule associated protein-2 (MAP-2). These results confirm earlier observation of the close temporal relationship between increased cytoskeletal protein phosphorylation and the development and OPIDN.
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PMID:Biochemical changes in sciatic nerve of hens treated with tri-o-cresyl phosphate: increased phosphorylation of cytoskeletal proteins. 133 13

The influence of socialization of chickens on response to exogenous substances in the presence and absence of stress was examined. Chickens of both sexes were habituated to human beings (socialized) by being talked to and offered food from the hand of the caretaker. After 19 w, half the socialized group and half the unsocialized group were subjected to stress (loud noises for 120 sec twice daily) for 2 w. At the end of this period, response to 37 mg pentobarbital/kg iv was evaluated by length of sleeping time. Males slept longer than females, and males that were socialized but not stressed slept significantly longer than other males. Stress and socialization did not significantly affect pentobarbital sleeping time in females. This indicated that response to pentobarbital was dependent on sex and on socialization, with the most notable effects occurring in socialized males. Socialized and nonsocialized, stressed and unstressed male and female chickens were also administered a single po dose of 360 mg tri-ortho-tolyl phosphate (TOTP)/kg. This organophosphorus ester induced a delayed neuropathy that caused ataxia in all the chickens. The ataxia was significantly more pronounced earlier in males than in females, although the sex difference became insignificant 18 d after dosing. Socialized chickens were ultimately more affected. Noise stress did not affect TOTP-induced ataxia. This indicated that response to an organophosphate neurotoxicant was also dependent on sex and socialization, with the most notable effects again seen in socialized males. Response to endogenous substances in chickens depends both on sex and on familiarity to humans.
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PMID:Role of socialization, stress and sex of chickens on response to anesthesia and on response to an organophosphate neurotoxicant. 150 73

Effects of administration of triflupromazine were evaluated in 11 adult domesticated camels (Camelus dromedarius) weighing 403 +/- 29.5 kg (Mean +/- SE). Six camels were used to evaluate sedative properties of the drug and its effects on haematological and blood biochemical parameters. In the remaining 5 camels, effects on haemodynamics, acid base status and blood gases were studied. In all the animals triflupromazine was administered intramuscularly in the gluteal region at the rate of 2 mg/kg. Camels voluntarily sat down 48.9 +/- 5.4 min after administration of the drug but stood up again if disturbed. Drowsiness, drooping of lower lip and salivation were evident. The animals stood on their own and started walking with ataxia after 159 +/- 7 min and recovered completely from the effect of drug within 259 +/- 23 min. The drug caused a significant tachycardia and a moderate hypotension. The decrease in central venous pressure was also significant. Rectal temperature, respiratory rate, acid base status, blood gases, haemoglobin concentration, packed cell volume, total erythrocyte count, total leucocyte count, differential leukocyte count, blood urea nitrogen, plasma alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, blood glucose and plasma concentrations of sodium, potassium, chloride and inorganic phosphate were not significantly affected by triflupromazine.
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PMID:Evaluation of triflupromazine as a sedative in camels (Camelus dromedarius). 177 79

Effects of organophosphorus esters (OPs) inducing delayed neuropathy in the adult hen have traditionally been evaluated by assessment of morphology and function of nerve and muscle in the rear limbs of animals exposed. In this study, organophosphorus-induced delayed neuropathy (OPIDN), including neuromuscular function and histology, were studied in vivo using sciatic nerve, tibial nerve and gastrocnemius muscle in anesthetized hens that had been administered phenyl saligenin phosphate (PSP), 2.5 mg/kg by intramuscular injection. In addition, OPIDN was examined in vitro using the biventer cervicis nerve and muscle of the same adult hens. Both nerve-muscle preparations were used for construction of strength duration curves (SDC) on days 4-5, 7-8, and 15-16 after PSP; the biventer cervicis preparation was also used 21-22, 37 and 64 days after PSP administration. Histological examination was done at these same time periods. SDC revealed significant increases in excitability thresholds for preparations from hens receiving PSP only compared to preparations from control hens, or compared to preparations from hens treated with PSP and either nifedipine (1 mg/kg intramuscularly for 5 days), or verapamil (7 mg/kg intramuscularly for 4 days), with treatment beginning 24 hours before administration of PSP. Ataxia, which appeared 7-10 days after hens were given PSP, was less pronounced in hens given PSP plus either calcium channel blocker than in hens given PSP alone. Whether treatment was initiated before or after PSP, verapamil, a phenylalkylamine, reduced sensitivity of the biventer cervicis muscle to acetylcholine-induced stimulation. The dihydropyridine, nifedipine, was less effective at reducing muscle sensitivity to acetylcholine post-exposure than when used as a pretreatment. Lesions were extensive in the biventer cervicis nerve after PSP administration and modification by treatment with calcium channel blockers was evident.
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PMID:Modification of phenyl saligenin phosphate-induced delayed effects by calcium channel blockers: in vivo and in vitro electrophysiological assessment. 208 84

Indices of organophosphorus (OP)-induced delayed neuropathy (OPIDN) in the hen model have traditionally been restricted to the early inhibition of neuropathy target esterase (NTE) and ataxia with associated pathological changes in hind limb peripheral nerve which occur more than 7 days after OP exposure. The biventer cervicis nerve-muscle preparation was used to evaluate OPIDN in adult hens at various time periods after treatment with either the protoxicant tri-o-tolyl phosphate (TOTP), 360 mg/kg po, or the active congener phenyl saligenin phosphate (PSP), 2.5 mg/kg im. NTE activity was 21 and 48% of control for TOTP and PSP, respectively, 4 days after administration. Clinical signs were notable by 10 days and progressed in severity to paralysis by 21 days. Partial clinical recovery was evident at 37 days. Denervation hypersensitivity of biventer cervicis muscle to acetylcholine (ACh) was evident as early as 4 days following TOTP or PSP treatment. The sensitivity to ACh was greatest 21 days after OP administration, with partial recovery at 37 days. Strength-duration curves (SDC) of preparations from OP-treated hens showed an increase in excitability thresholds and elevated rheobase with shorter chronaxie than did preparations from controls as early as 4 days following treatment with either compound. SDC at 37 days indicated partial reinnervation. Peripheral nerve myelinated fiber degeneration and regeneration consistent with these physiological changes was seen on histopathological examination. This study suggests that the biventer cervicis nerve-muscle preparation may prove useful for detection of functional and morphological changes that occur during the interval between NTE inhibition and appearance of clinical deficits.
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PMID:Use of the biventer cervicis nerve-muscle preparation to detect early changes following exposure to organophosphates inducing delayed neuropathy. 237 92

Chick embryos were injected on incubation Day 14 with 62 microliter of triorthocresyl phosphate (TOCP)/kg egg. Muscles of the leg were examined from 5 to 25 days after hatching. The sartorius from the thigh and the external gastrocnemius and peroneus longus from the tibial leg region were compared for muscle fiber size and end-plate length over this period. Treated chicks showed no acute toxic effects or overt ataxia and were equal in body weight to controls. At 5, 15, and 25 days after hatching, morphologic alterations consistent with denervation were detected. Muscle fibers were smaller than controls on Day 5 and were hypertrophic on Days 15 and 25. On Day 5 growth of fibers was retarded, an effect consistent with denervation, and the subsequent hypertrophy is predicted as compensation for denervated fibers. Small end plates were seen on Day 15, characteristic of end plates that were delayed in development by denervation. Each of these differences was greater in the tibial muscles than in the more proximally located sartorius. This is consistent with a distal neuropathy, such as that caused by TOCP in adult hens. Some recovery was apparent at the low dose 25 days after hatching. It is suggested that this resulted from reinnervation by repaired axons. This study of the myoneural apparatus and muscle fiber response to TOCP adds evidence to the possibility that the developing chick embryo may develop delayed neuropathy from organophosphorus compounds which produce this effect in adult hens.
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PMID:Morphologic alterations in leg muscles of chicks treated with triorthocresyl phosphate in ovo. 241 88

Verapamil, a calcium channel blocker, was administered to adult white leghorn hens to determine if inhibition of calcium entry could alter delayed neuropathy induced by administration of phenyl saligenin phosphate (PSP). Verapamil was given im in doses of 7 mg/kg/day for 4 days beginning 24 hr before administration of PSP (2.5 mg/kg im). Ataxia was less pronounced in hens given PSP plus verapamil than in hens given PSP alone during observations made 8-28 days after PSP administration. Myelinated fiber lesions were less extensive and regeneration more notable in the biventer cervicis nerve in chickens given PSP plus verapamil, with samples obtained both 17 and 28 days after PSP. In the absence of verapamil, rheobase and chronaxie values of strength-duration curves were higher and shorter, respectively, and sensitivity to acetylcholine was increased in biventer cervicis nerve-muscle preparations from hens given PSP. Verapamil did not alter PSP-induced inhibition of neurotoxic esterase, indicating that the mechanism involved in amelioration of these indices of delayed neuropathy was not associated with initial enzyme inhibition caused by this organophosphorus ester.
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PMID:Effect of verapamil on organophosphorus-induced delayed neuropathy in hens. 255 27


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