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)

Oral administration of 0.5 mg/kg/day monocrotophos for 28 days caused death in one out of three animals. A dose of 2.0 mg/kg/day of monocrotophos was 100 percent lethal within 8-12 days after start of insecticide administration. Clinical symptoms were mainly characterised by ataxia, knuckling of limbs, progressive paralysis and prostration. Monocrotophos at both doses caused significant inactivation of erythrocyte cholinesterase (29.4-50.8%) and caused significant elevation in the serum levels of aspartate and alanine aminotransferases.
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PMID:Subacute toxicity of monocrotophos and its influence on circulating enzymes of Bubalus bubalis. 341 31

Potassium picloram was administered either by gavage (acute studies) or in drinking water to male and female Sprague-Dawley-derived rats (14-day and 90-day studies). The acute oral LD50 was 950 mg/kg (812-1120) for males and 686 mg/kg (599-786) for females. Depression, prostration, ataxia, tremors, and convulsions preceded death. There were no consistent biologically significant compound-related effects in rats that received 60, 190, 600 mg potassium picloram/kg/day for 14 days. In the subchronic study, rats received 60, 190, 600, or 1070 mg potassium picloram/kg/day in drinking water for 90 consecutive days. There were only 4 male and 2 female survivors out of 20 rats of each sex at the 1070 mg/kg dose and 16 male and 18 female survivors at the 600 mg/kg dose. Mortality was dose dependent. Administration of picloram appeared to exacerbate renal and hepatic lesions commonly noted in rats of this age. For example, at levels up to 1070 mg/kg mild lesions in the kidney of treated rats, especially in males at 600 mg/kg, were noted. Also noted were an increased incidence of mononuclear liver foci in male rats that received 190 and 600 mg/kg and an increased severity of mononuclear liver foci in females that received 600 mg/kg. There were no other consistent biologically significant compound-related effects. No specific organ site toxicity could be identified in these studies. Toxicity from exposure to picloram in drinking water is apparently low.
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PMID:Acute, 14-day repeated dosing, and 90-day subchronic toxicity studies of potassium picloram. 378 Nov 36

Between 1976 and 1981 a specific neurological disorder of sheep was observed in Ghana. It was encountered on eight properties on some of which it was responsible for losses of up to 72 per cent of the sheep stock in some years. The condition affected mainly adult ewes, and was characterised clinically by a brief period of ataxia, followed by paresis prostration and death in four to five days. Morphological examination of nine affected animals revealed significant lesions only in the central nervous system. These consisted of oedema of the intracellular glial compartment and bilateral, sometimes symmetrical, foci of spongy transformation, malacia and haemorrhage in the grey matter of the brain stem, cerebellum and spinal cord. The aetiology of ataxia/paresis syndrome was not determined but some possibilities are discussed in the context of other naturally occurring and experimental focal malacic disorders in animals.
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PMID:Ataxia/paresis syndrome of sheep in West Africa associated with bilateral multifocal cerebrospinal poliomalacia. 397 53

Trimethyltin chloride (TMT) was given to Syrian hamsters, gerbils and marmosets, and the changes in the brain were studied 1 day to 7 weeks later by light and electron microscopy. Within the marmoset brain, TMT was found to be uniformly distributed, similar to that in the rat. In all three species, signs of poisoning included whole-body tremors and prostration, while death might occur in 3-4 days; in marmosets ataxia, agitation, aggression and occasional fits were also observed. Bilateral symmetrical neuronal necrosis and chromatolysis were seen in the majority, which involved the hippocampus, pyriform cortex, amygdaloid nucleus, neocortex, various brain stem nuclei and in marmosets the retina. The probably lethal dose of TMT in all three species is approximately 3 mg kg-1, while the LD50 for the rat is 12.6 mg kg-1. The lower figure is probably related to lack of binding to haemoglobin in contrast to the binding in the rat. TMT does not bind to human haemoglobin and thus the predicted lethal dose for humans may be about 3 mg kg-1 (15.1 mumol kg-1), while the dose required to produce neuronal damage could well be less.
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PMID:The neurotoxicity of trimethyltin chloride in hamsters, gerbils and marmosets. 642 93

The results of a broad pharmacological screening on 1-[(2,4-dichlorophenyl)-methyl] -1H-indazole-3-carboxylic acid ( lonidamine ) a new antitumour agent which also possesses antispermatogenic and embryotoxic effects, are reported. Lonidamine does not affect general behaviour and autonomic functions and is devoid of anticonvulsant, anti-reserpine, anti-apomorphine, anti-amphetamine, antitremor , antipyretic, antiinflammatory and analgesic effects. It also lacks those side effects which are considered characteristic of different antitumour agents, such as thymus and spleen atrophy, delay in skin wound healing and damage to the gastrointestinal mucosa. At doses 40 times higher than that of hydrochlorothiazide, lonidamine produces diuretic effects. The practical importance of these findings in the current therapeutic use of lonidamine appears to be limited. The most typical signs of acute intoxication produced by high doses of lonidamine are salivation, lacrimation, diarrhea, ataxia, muscle rigidity and prostration with superimposed convulsions.
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PMID:Pharmacological investigations on lonidamine. 654 Jan 4

Clinical signs and lesions of levamisole toxicosis include: nausea, vomiting, increased salivation, frequent urination and defecation, colic, dizziness, headache, muscle tremors, ataxia, anxiety, hyperesthesia with irritability, clonic convulsions, depression, rapid respiration, dyspnea, prostration, collapse, hemorrhages in the subepicardium and thalamus, enteritis, hepatic degeneration and necrosis, and splenic congestion. Most of these signs and lesions are similar to those observed in nicotine poisoning. Levamisole causes vasopressor and panting effects which are blocked by ganglionic blocking agents hexamethonium and mecamylamine but are not blocked by atropine. The vasopressor effect of levamisole is blocked by alpha-adrenergic antagonists phentolamine and dibenamine; however, the respiratory effect of levamisole is not affected by these alpha-adrenergic antagonists. Repeated IV injections of levamisole cause a tachyphylactic response. With levamisole-induced tachyphylaxis, the effects of other ganglionic stimulants dimethylpiperazinium and nicotine are also abolished. Levamisole causes an electroencephalographic arousal which is antagonized by atropine sulfate and mecamylamine. There is also a structural similarity of levamisole to nicotine. These studies suggest that levamisole is a nicotine-like compound. Possible treatment of levamisole poisoning is discussed. Drug interactions of levamisole with organophosphates and anthelmintics, eg, pyrantel, methyridine, and diethylcarbamazine, are also discussed.
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PMID:Toxicity and drug interactions of levamisole. 721 95

Diisopropyl methylphosphonate (DIMP), and dicyclopentadiene [3a,4,7,7a-tetrahydro-4,7-methyanoindene] (DCPD), were found as contaminants of groundwater in Colorado. Since there was a potential for cattle to be exposed to these chemicals by drinking well water, a study of their effects was initiated. Eight-to-ten week old calves were given a single dose of either DIMP at 62.5, 125, 250, 500 and 1000 mg/kg of body weight (b.w.) or DCPD at 250, 500, 1000 or 2000 mg/kg of b.w. The calves given DIMP developed tympanitis and ataxia, followed by depression, prostration, and death within two hr after dosing. A slight but significant increase in activated partial thromboplastin time was the only change observed in any of the clinical pathologic parameters. The only gross pathologic changes were acute gastroenteritis with hemorrhages in calves given 1000 mg/kg of b.w. Mild signs of intoxication, ataxia and excess salivation, were observed in calves given 250 mg of DCPD/kg of b.w. At higher doses, these signs were intensified; in addition, calves fell and, while prostrate, exhibited running movements and tonic, clonic spasms. The severity of the signs observed increased as the dose of DCPD increased. All calves given 2000 mg/kg of b.w. and one calf given 1000 mg/kg of b.w. died before seven days after dosing. The only clinical pathologic changes found were increased serum levels of creating phosphokinase, glutamic-oxalacetic transaminase, and glutamic pyruvic transaminase. The only consistent gross pathologic change was congestion in a variety of tissues in calves given 2000 mg/kg of b.w. A variety of histologic changes were observed in tissues from calves treated with both chemicals. However, these changes were not consistent for any one dose level and were not dose dependent. DIMP was slightly toxic for calves, since no signs of intoxication were observed at doses less than 1000 mg/kg of b.w. DCPD exerted detrimental effects on calves at 250 mg/kg of b.w. and was classified as moderately toxic.
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PMID:Toxicologic evaluation of diisopropyl methylphosphonate and dicyclopentadiene in cattle. 730 51

The developmental toxicity of the anticonvulsant compound, ralitoline, was investigated in Sprague-Dawley rats administered oral doses of 0, 15, 60, 120, 180, or 240 mg/kg on days 6 through 15 of gestation. An untreated control group and a vehicle control group pair-fed to the high dose group were included. Maternal and fetal parameters were evaluated on day 21 of gestation. Fetuses were examined for external, visceral, and skeletal malformations and variations. Maternal death occurred at 180 and 240 mg/kg. Dose-dependent decreases in body weight, food consumption, and water consumption were observed at 60 mg/kg and above. Body weight gain during treatment was similar in the pair-fed and 240 mg/kg groups. Dose-related CNS signs (hypoactivity, ataxia, prostration, and/or convulsions) were observed at 60 mg/kg and above. Decreased numbers of live fetuses and increased postimplantation loss were observed in a dose-related manner at 120, 180, and 240 mg/kg while no changes occurred in pair-fed controls. Fetal body weights and placental weights were decreased in pair-fed controls and in the 120, 180, and 240 mg/kg groups. The percent fetuses per litter, and the percent litters with external/visceral malformations, were significantly increased at 120, 180, and 240 mg/kg compared with vehicle and pair-fed controls. Dose-related increases in cardiovascular malformations, specifically of the aortic arch (interrupted, stenotic, extra vessel), were apparent at 120 mg/kg and above. The incidence of skeletal variations was increased at 120 mg/kg and above.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Developmental toxicity study in rats treated with the anticonvulsant, ralitoline. 759 53

Five groups of 25 Fischer 344 rats of each sex were exposed for 6 h to isopropanol vapor at 0, 500, 1500, 5000 or 10,000 ppm. Behavioral observations for 10 rats of each sex were made prior to and 1, 6, and 24 h after exposure. Motor activity was evaluated for 15 rats of each sex prior to and immediately following exposure. Exposure to isopropanol caused a spectrum of transient effects indicative of narcosis at 10,000 ppm and sedation at 5000 ppm. Prostration or severe ataxia, decreased arousal, slowed or labored respiration, decreased neuromuscular function, hypothermia and loss of reflex function were observed 1 and 6 h after exposure to 10,000 ppm isopropanol vapor. Similar, but less severe, alterations were observed in animals in the 5000 ppm exposure group 1 h after exposure. Exposure concentration-related decreases in motor activity were observed in males and females in the 5000 and 10,000 ppm groups and slight decreases in motor activity were observed in males in the 1500 ppm group. Animals in the 1500 and 5000 ppm exposure groups recovered from these motor activity effects within 5 h. Based on this study, exposure of male and female rats to isopropanol vapor produces transient, concentration-related narcosis and/or sedation at concentrations of 5000 and 10,000 ppm and minor decreases in motor activity in males at a concentration of 1500 ppm. The no-observed-effect level (NOEL) for this was 500 ppm isopropanol.
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PMID:Isopropanol: acute vapor inhalation neurotoxicity study in rats. 778 62

1. A single administration of the ganglion blocker, chlorisondamine (10 mg kg-1, s.c.) is known to produce a quasi-irreversible blockade of the central actions of nicotine in the rat. The mechanism of this persistent action is not known. It is also unclear whether chlorisondamine can block neuronal responses to excitatory amino acids and whether chronic blockade of nicotinic responses also occurs in the periphery. 2. Acute administration of chlorisondamine (10 mg kg-1, s.c.) to rats resulted in a blockade of central nicotinic effects (ataxia and prostration) when tested 1 to 14 days later, but caused no detectable cell death in tissue sections sampled throughout the rostrocaudal extent of the brain which were stained in order to reveal neuronal degeneration. 3. Long-term blockade of central nicotinic effects by chlorisondamine was not associated with significant alterations in the density (Bmax) of high-affinity [3H]-nicotine binding to forebrain cryostat-cut sections. 4. In cultured dissociated mesencephalic cells of the foetal rat, chlorisondamine and mecamylamine inhibited [3H]-dopamine release evoked by N-methyl-D-aspartate (NMDA, 10(-4) M), but only at high concentrations (IC50 approx. 600 and 70 microM, respectively). A high concentration of chlorisondamine (10(-3) M) had no effect on responses to quisqualate (10(-5) M) and only slightly reduced responses to kainate (10(-4) M). Mecamylamine (10(-3) M) was ineffective against both agonists. 5. In adult rat hippocampal slices, chlorisondamine depressed NMDA receptor-mediated synaptically-evoked field potentials, but again only at high concentrations (10(-4)-10(-3) M). Synaptic responses that were mediated by non-NMDA excitatory amino acid receptors were less affected. 6. In rat isolated superior cervical ganglion, electrically-evoked synaptic transmission was reduced 1 h after acute in vivo administration of chlorisondamine (0.1 mg kg-1, s.c.). However, in vivo administration of a higher dose (10 mg kg-1, s.c.) did not significantly affect ganglionic transmission when tested two weeks later, despite the continued presence of central nicotinic blockade.7. These results indicate that the persistent CNS nicotinic blockade by chlorisondamine is not accompanied by changes in nicotinic [3H]-nicotine binding site density or by neuronal degeneration in the brain; that at doses sufficient to produce nicotinic receptor blockade, chlorisondamine acts in a pharmacologically selective manner; and that chronic central blockade is not accompanied by long-term peripheral ganglionic blockade.
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PMID:The pharmacology of the nicotinic antagonist, chlorisondamine, investigated in rat brain and autonomic ganglion. 791 13


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