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)

Fifty-seven cases of meprobamate ingestion from 1974 through 1979 were reviewed. Serum meprobamate concentrations, clinical findings, and epidemiologic data were studied to determine the present status of the abuse of this compound. The average patient was a 37-year-old woman who ingested meprobamate and at least one other drug (usually a benzodiazepine, a barbiturate, ethanol, or an opiate) in a suicide attempt of gesture. She arrived at the hospital either alert or lethargic with equal frequency. Half of the time she was seen only in the emergency room, and half of the time she was hospitalized. She was usually treated with supportive care alone and survived the ingestion. Serum meprobamate concentrations exceeding 12 mg/dl were consistent with coma. Dysarthria, hypotension, tachycardia, and ataxia were the most common physical findings. Meprobamate addiction was present in six patients.
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PMID:The present status of meprobamate ingestion. A five-year review of cases with serum concentrations and clinical findings. 745 16

THE ROLE OF IONIC CHANNEL DYSFUNCTION: During various neurological diseases has been evoked for many years on electro-physiological data. Molecular biology has led to great progress in neurology, and can be considered "functional" since it is surpasses the classical anatomo-clinical methods. IONIC CHANNEL DYSFUNCTION: Can be determined genetically, resulting from the mutation of a gene code of a channel sub-unit. CHANNELOPATHIES ARE RESPONSIBLE: For muscular diseases (myotonia, familial periodic paralysis, malignant hyperthermia and congenital myasthenia), but also for central nervous system disorders such as familial hemiplegic migraine, hereditary paroxystic ataxia and certain forms of Mendel's law hereditary epilepsy. ACQUIRED IONIC CHANNEL DYSFUNCTION: Resulting from auto-immune aggression is implied in diseases such as Lambert-Eaton's myasthenic syndrome and Isaac's neuromyotonia syndrome. It probably plays a part in the clinical, and particularly the sensitive expression (paresthesia and pain) of some peripheral neuropathies and certain central nervous system affections, such as multiple sclerosis.
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PMID:[Ion channel abnormalities ("channelopathies") in neurologic diseases]. 1188 65

Hexachloroethane is used in organic synthesis as a retarding agent in fermentation, as a camphor substitute in nitrocellulose, in pyrotechnics and smoke devices, in explosives, and as a solvent. In previous long-term gavage studies with B6C3F1 mice and Osbourne-Mendel rats (78 weeks of exposure followed by 12-34 weeks of observation), hexachloroethane caused increased incidences of hepatocellular carcinomas in mice. However, survival of low and high dose rats was reduced compared with that of vehicle controls, and the effects on rats were inconclusive. Therefore, additional toxicology and carcinogenesis studies were conducted in F344/N rats by administering hexachloroethane (approximately 99% pure) in corn oil by gavage to groups of males and females for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and in Chinese hamster ovary (CHO) cells. Urinalysis was performed in conjunction with the 13-week studies. Sixteen-Day Studies: In the 16-day studies (dose range, 187-3,000 mg/kg), all rats that received 1,500 or 3,000 mg/kg and 1/5 males and 2/5 females that received 750 mg/kg died before the end of the studies. Final mean body weights of rats that received 750 mg/kg were 25% lower than that of vehicle controls for males and 37% lower for females. Compound-related clinical signs seen at 750 mg/kg or more included dyspnea, ataxia, prostration, and excessive lacrimation. Other compound-related effects included hyaline droplet formation in the tubular epithelial cells in all dosed males and tubular cell regeneration and granular casts in the tubules at the corticomedullary junction in the kidney in males receiving 187 and 375 mg/kg. Thirteen-Week Studies: In the 13-week studies (dose range, 47-750 mg/kg), 5/10 male rats and 2/10 female rats that received 750 mg/kg died before the end of the studies. The final mean body weight of male rats that received 750 mg/kg was 19% lower than that of vehicle controls. Compound-related clinical signs for both sexes included hyperactivity at doses of 94 mg/kg or higher and convulsions at doses of 375 or 750 mg/kg. The relative weights of liver, heart, and kidney were increased for exposed males and females. Kidney lesions were seen in all dosed male groups, and the severity increased with dose. Papillary necrosis and tubular cell necrosis and degeneration in the kidney and hemorrhagic necrosis in the urinary bladder were observed in the five male rats that received 750 mg/kg and died before the end of the studies; at all lower doses, hyaline droplets, tubular regeneration, and granular casts were present in the kidney. No chemical-related kidney lesions were observed in females. Foci of hepatocellular necrosis were observed in several male and female rats at doses of 188 mg/kg or higher. Dose selection for the 2-year studies was based primarily on the lesions of the kidney in males and of the liver in females. Studies were conducted by administering hexachloroethane in corn oil by gavage at 0, 10, or 20 mg/kg body weight, 5 days per week, to groups of 50 male rats. Groups of 50 female rats were administered 0, 80, or 160 mg/kg on the same schedule. Body Weight and Survival in the Two-Year Studies: Mean body weights of high dose rats were slightly (5%-9%) lower than those of vehicle controls toward the end of the studies. No significant differences in survival were observed between any groups of rats (male: vehicle control, 31/50; 10 mg/kg, 29/50; 20 mg/kg, 26/50; female: vehicle control, 32/50; 80 mg/kg, 27/50; 160 mg/kg, 32/50). Nonneoplastic and Neoplastic Effects in the Two-Year Studies: Incidences of kidney mineralization (vehicle control, 2/50; low dose, 15/50; high dose, 32/50) and hyperplasia of the pelvic transitional epithelium (0/50; 7/50; 7/50) were increased in dosed male rats. Renal tubule hyperplasia was observed at an increased incidence in high dose male rats (2/50; 4/50; 11/50). These lesions have been described as characteristic of the hyaline droplet nephropathy that is associated with an accumulation of liver-generateted with an accumulation of liver-generated a2μ-globulin in the cytoplasm of tubular epithelial cells. The severity of nephropathy was increased in high dose male rats (moderate vs. mild), and the incidences and severity of nephropathy were increased in dosed females (22/50; 42/50; 45/50). The incidences of adenomas (1/50; 2/50; 4/50), carcinomas (0/50; 0/50; 3/50), and adenomas or carcinomas (combined) (1/50; 2/50; 7/50) of the renal tubule were also increased in the high dose male group. One of the carcinomas in the high dose group metastasized to the lung. No compound-related neoplasms were observed in females. The incidence of pheochromocytomas of the adrenal gland in low dose male rats was significantly greater than that in vehicle controls (15/50; 28/50; 21/49), and the incidences for both dosed groups were greater than the mean historical control incidence (28% ± 11%). Genetic Toxicology: Hexachloroethane was not mutagenic in S. typhimurium strains TA98, TA100, TA1535, or TA1537 when tested with and without exogenous metabolic activation. In CHO cells, hexachloroethane did not induce chromosomal aberrations with or with out metabolic activation but did produce sister chromatid exchanges in the presence of exogenous metabolic activation. Audit: The data, documents, and pathology materials from the 2-year studies of hexachloroethane have been audited. The audit findings show that the conduct of the studies is documented adequately and support the data and results given in this Technical Report. Conclusions: Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenic activity of hexachloroethane for male F344/N rats, based on the increased incidences of renal neoplasms. The marginally increased incidences of pheochromocytomas of the adrenal gland may have been related to hexachloroethane administration to male rats. There was no evidence of carcinogenic activity of hexachloroethane for female F344/N rats administered 80 or 160 mg/kg by gavage for 103 weeks. The severity of nephropathy and incidences of linear mineralization of the renal papillae and hyperplasia of the transitional epithelium of the renal pelvis were increased in dosed male rats. The incidences and severity of nephropathy were increased in dosed female rats. Synonyms: carbon hexachloride; ethane hexachloride; hexachlorethane; hexachloroethylene; 1,1,1,2,2,2-hexachloroethane; perchloroethane Trade Names: Avlothane; Distokal; Distopan; Distopin; Egitol; Falkitol; Fasciolin; Mottenhexe; Phenohep
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PMID:Toxicology and Carcinogenesis Studies of Hexachloroethane (CAS No. 67-72-1) in F344/N Rats (Gavage Studies). 1269 80

A bioassay of technical-grade toxaphene for possible carcinogenicity was conducted by administering the test chemical in feed to Osborne-Mendel rats and B6C3F1 mice. Groups of 50 rats of each sex were administered toxaphene at one of two doses for 80 weeks, then observed for 28 or 30 weeks. Time-weighted average doses for males were 556 or 1,112 ppm; for females they were 540 or 1,080 ppm. Matched controls consisted of groups of 10 untreated rats of each sex; pooled controls consisted of the matched-control groups for toxaphene combined with 45 untreated male and 45 untreated female rats from similar bioassays of five other test chemicals. All surviving rats were killed at 108-110 weeks. Groups of 50 mice of each sex were administered toxaphene at one of two doses for 80 weeks, then observed for 10 or 11 weeks. Time-weighted average doses were 99 or 198 ppm for both males and females. Matched controls consisted of groups of 10 untreated mice of each sex; pooled controls consisted of the matched-control groups for toxaphene combined with 40 untreated male and 40 untreated female mice from similar bioassays of four other test chemicals. All surviving mice were killed at 90-91 weeks. Mean body weights attained by low- and high-dose female rats and high-dose male mice were lower than those of matched controls, but weights of other dosed groups were essentially unaffected by the toxaphene. Other clinical signs of toxicity in rats included generalized body tremors at week 53 in high-dose male and female animals, and later, leg paralysis, ataxia, epistaxis, hematuria, and vaginal bleeding, predominantly in the dosed groups of rats of each sex. Abdominal distention, diarrhea, dyspnea, and rough hair coats were common to both dosed rats and dosed mice. There were dose-related decreases in survival rates in mice but not in rats. Sufficient numbers of both rats and mice were at risk for the development of late-appearing tumors. In the male rats, the incidence of follicular-cell carcinomas or adenomas of the thyroid was dose related (P=0.007) using the pooled controls (matched controls 1/7, pooled controls 2/44, low-dose 7/41, high-dose 9/35). In the females, the incidence of follicular-cell adenomas of the thyroid was dose related using either the matched (P=0.022) or pooled (P=0.008) controls (matched controls 0/6, pooled controls 1/46, low-dose 1/43, high-dose 7/42). Direct comparisons of dosed and pooled-control groups but not matched controls showed significantly increased incidences of follicular-cell carcinomas or adenomas in the high-dose males (P=0.008) and of follicular-cell adenomas in the high-dose females (P=0.021). Two follicular-cell tumors in the high-dose males were carcinomas; all other follicular-cell tumors in the rats were adenomas. In the mice, the incidence of hepatocellular carcinomas was dose related (P<0.001) for both males (matched controls 0/10, pooled controls 4/48, low-dose 34/49, high-dose 45/46) and females (matched controls 0/9, pooled controls 0/48, low-dose 5/49, high-dose 34/49), using either matched or pooled controls. Direct comparisons showed that the incidences of hepatocellular carcinomas in low- and high-dose male mice and high-dose female mice were all significantly higher (P<0.001) than those in the respective matched or pooled controls. Statistical significance was maintained when the incidence of hepatocellular carcinomas was combined with that of neoplastic nodules of the liver. It is concluded that under the conditions of this bioassay, toxaphene was carcinogenic in male and female B6C3F1 mice, causing increased incidences of hepatocellular carcinomas. The test results also suggest carcinogenicity of toxaphene for the thyroid of male and female Osborne-Mendel rats.
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PMID:Bioassay of toxaphene for possible carcinogenicity. 1284 70