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)

Susceptibility of sheep to oral administration of Citrullus colocynthis fruits, Nerium oleander leaves or their mixture is described in 12 sheep assigned as untreated controls, C. colocynthis-treated at 0.25g/kg/day, N. oleander-treated at 0.25g/kg and plant mixture-treated at 0.25g of C. colocynthis/kg plus 0.25g of N. oleander/kg. The daily use of 0.25g of C. colocynthis/kg for 42 days was not fatal to sheep and caused slight diarrhoea, catarrhal enteritis, centrilobular hepatocellular fatty change and degeneration of the renal tubular cells. Single oral doses of 0.25g of N. oleander/kg were lethal to sheep within 18-24h and caused uneasiness, grinding of the teeth, dyspnoea, anorexia, frequent urination, ruminal bloat, ataxia and recumbency before death. The main lesions were widespread congestion and haemorrhage, pulmonary cyanosis and emphysema and severe hepatonephropathy. Rapid death was also observed in sheep receiving single doses of the mixture of the two plants. Effects were correlated with changes in the activities of serum lactic dehydrogenase (LDH) and aspartate transaminase (AST) and concentrations of cholesterol, bilirubin, total protein, albumin, globulin and urea and haematological parameters.
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PMID:Response of Najdi sheep to oral administration of Citrullus colocynthis fruits, Nerium oleander leaves or their mixture. 1132 8

An approximately 8-week-old pet Syrian hamster (Mesocricetus auratus) with a 1-week history of dyspnea, hyporexia, and ataxia was submitted for necropsy. On gross examination, the hamster had multiple abdominal adhesions and enlargement of the mesenteric lymph node. Histologic evaluation revealed multicentric lymphoma of the liver, jejunum, mesenteric lymph node, testicular fat pad, and epididymis. Based on the hamster's age and the type and distribution of the lymphoma, a presumptive diagnosis of hamster polyomavirus-induced lymphoma was made. A specific polymerase chain reaction (PCR) was developed, which confirmed the diagnosis. An in situ PCR demonstrated hamster polyomavirus DNA within lymphocytes of the multicentric lymphoma and renal tubular epithelial cells and within clusters of enterocytes in the jejunum. These data are consistent with environmental dissemination of hamster polyomavirus virions through the renal tubular epithelium and into the urine and with fecal shedding of hamster polyomavirus virions; however, additional studies will be needed to confirm these observations.
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PMID:Hamster polyomavirus infection in a pet Syrian hamster (Mesocricetus auratus). 1146 79

Moxidectin is a macrolide endectocide available as a 2% equine oral gel in the US. This report presents clinical signs of moxidectin toxicosis and its treatment in equines as reported to the ASPCA Animal Poison Control Center (APCC) from January 1998 to December 2000. Nine cases of moxidectin overdose in equines occurred: 5 had signs of toxicosis such as coma, dyspnea, depression, ataxia, tremors, seizures, or weakness. The approximate dose of moxidectin at which these signs were observed ranged from 1.0 to 5.1 mg/kg. The 4 equines that ingested moxidectin between 0.9 mg/kg to 1.7 mg/kg did not show signs of toxicosis. Clinical signs were seen within 6-22 h and lasted for 36-168 h. Only 1/5 clinical equines was an adult, the others were < 4 month of age. This study supports earlier report that young foals are more susceptible to moxidectin toxicosis. All 4 equines with known outcomes recovered with treatment that included decontamination, seizure control, thermoregulation, fluid therapy, and supportive care.
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PMID:A review of moxidectin overdose cases in equines from 1998 through 2000. 1213 74

We present the first reported study of Ruta graveolens toxicity in 7-8-month-old Nubian goats. Oral administration of 5 g/kg bw per day of R. graveolens leaves caused tremor, dyspnoea, frequent urination, incoordination of movement, ataxia and recumbency, with death after 1-7 days. In goats receiving oral doses of 1 g/kg bw per day of the leaves, the course of toxicity was prolonged and the animals had pallor of the visible mucous membranes and loss in condition; one died on day 17, the others being slaughtered on days 41 and 46. The clinical effects were correlated with pathological changes in various organs, alterations in serum aspartate transaminase, creatine kinase, total protein, cholesterol, urea and other serum constituents, haematological values and the concentrations in the tissues of copper, iron, zinc, manganese, calcium and phosphorus.
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PMID:Preliminary observations on experimental Ruta graveolens toxicosis in Nubian goats. 1216 28

Methylene bis(thiocyanate) is used as a biocide in a number of applications. Its major use is in water cooling systems and paper mills as an inhibitor of algae, fungi, and bacteria. Methylene bis(thiocyanate) was selected for study because of the potential for human exposure to the compound and because of the interest in organothiocyanates as a chemical class. Toxicity studies of methylene bis(thiocyanate) (approximately 98% pure) were conducted with male and female F344/N rats and B6C3F1 mice; the compound was administered to the animals by gavage in an aqueous methyl cellulose vehicle for 2 weeks or 13 weeks. In addition to these studies, the genetic toxicity of methylene bis(thiocyanate) was evaluated by determining mutagenicity in Salmonella typhimurium with and without S9 activation and frequency of micronucleated normochromatic erythrocytes in the peripheral blood of mice. In the 2-week studies, groups of five rats and five mice per sex were administered methylene bis(thiocyanate) at concentrations of 0, 10, 20, 40, 80, and 160 mg/kg body weight. All animals in the two highest dose groups (80 and 160 mg/kg) died by Day 2 of the studies. Except for one female rat, all animals receiving 40 mg/kg methylene bis(thiocyanate) also died before the end of the studies. Few significant gross lesions were observed in the 80 and 160 mg/kg groups. Clinical observations were similar to those reported for cyanide toxicity and included dyspnea, tremors. and ataxia. The stomach, which was identified as the target organ in rats and mice surviving for at least 24 hours, had necrotic inflammatory lesions of the mucosal surface of both the glandular and nonglandular portions. In the 13-week studies, groups of 10 rats and 10 mice per sex were administered methylene bis(thiocyanate) at concentrations of 0, 1, 2, 4, 8, and 16 mg/kg body weight. In the rat study, deaths occurred in the 2, 4, 8, and 16 mg/kg groups, while in the mouse study, deaths occurred only in the 8 and 16 mg/kg groups. As in the 2-week studies, the stomach was identified as the primary target organ. However, the lower doses administered in the 13-week studies resulted in gastric effects that were limited to the forestomach and consisted primarily of squamous mucosal hyperplasia and hyperkeratosis. Rats receiving the higher doses of methylene bis(thiocyanate) developed a mild anemia, and sperm motility was decreased in male rats receiving 4 or 8 mg/kg. Methylene bis(thiocyanate) was not mutagenic in S. typhimurium, with or without S9 activation. The frequencies of micronucleated normochromatic erythrocytes in the peripheral blood of dosed and control mice were similar. Chemical disposition studies of [14C]-labeled methylene bis(thiocyanate) were conducted in male F344 rats. In these studies, more than 90% of the administered radioactivity was eliminated in 48 hours. However, as the dose was increased from 0.2 to 1 to 10 mg/kg, greater percentages of the administered radioactivity remained in the tissues. Blood cyanide concentrations were increased shortly after the administration of 10 mg/kg [14C]-methylene bis(thiocyanate) but were similar to control values 2 hours after dosing. Overall, the toxic effects of methylene bis(thiocyanate) were consistent with those of an irritant chemical administered by gavage. There was also some indication that the release of cyanide may result in acute toxicity at the higher dose levels used in these studies. The no-observed-adverse-effect level for forestomach lesions in the 13-week studies was 4 mg/kg for male rats and 2 mg/kg for female rats and male and female mice. Synonyms: MBT; methylene-bis-thiocyanate; methylene bisthiocyanate; methylene dithiocyanate.
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PMID:NTP technical report on the toxicity studies of Methylene Bis(thiocyanate) (CAS No. 6317-18-6) Administered by Gavage to F344/N Rats and B6C3F1 Mice. 1220 92

The toxic effects of oral administration of 0.25 g/kg Nerium oleander leaves, 0.25 g/kg Rhazya stricta leaves or their mixture at 0.25 g/kg N. oleander leaves plus 0.25 g/kg R. stricta leaves on Najdi sheep were investigated. Daily oral dosing of R. stricta leaves for 42 days was not fatal to sheep while single oral doses of either N. oleander leaves or the mixture with R. stricta leaves proved fatal to animals within 24 hours with dyspnea, grunting, salivation, grinding of the teeth, ruminal bloat, frequent urination, ataxia and recumbency prior to death. The main lesions were widespread congestion or hemorrhage, pulmonary cyanosis, emphysema, bronchotracheal froths, and hepatonephropathy. The clinical and pathological changes were correlated with alterations in serum LDH and AST activities and concentrations of cholesterol, bilirubin, urea, total protein, albumin, and globulin and hematological values.
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PMID:Toxicity of Nerium oleander and Rhazya stricta in Najdi sheep: hematologic and clinicopathologic alterations. 1223 14

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 a2&mu;-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&percnt; &plusmn; 11&percnt;). 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

Lymphomatoid granulomatosis (LYG)/angiocentric immunoproliferative lesions (AIL) consist of angiocentric and angiodestructive lymphoreticular proliferation predominantly involving the lungs and other extranodal sites, such as the central nervous system (CNS). This clinical entity is considered as a B cell process related to Epstein-Barr virus (EBV) infection and EBV positive diffuse large B-cell lymphoma. The CNS is involved in 20% of cases of LYG, but initial involvement is rare. In cases without pulmonary symptoms, diagnosis may be difficult. We report a rare case involving initial progression of CNS symptoms followed by a pulmonary abnormality.A 14-year-old girl suffered from high fever, ataxic gait and paraparesis. MRI revealed diffuse T2 high signals with multiple gadolinium enhancements in the cerebellum, brain stem and cerebral white matter. Her symptoms briefly improved after steroid therapy, but ataxia gradually progressed. Dyspnea due to pulmonary interstitial involvement appeared when she was 18 years old. Steroid therapy proved effective for respiratory symptoms. At 20 years old she suffered from disseminated intravascular coagulopathy (DIC) and hemophagocytic syndrome (HPS) with respiratory symptoms and repeated seizures. Her symptoms improved after the administration of cyclophosphamide. Mild hemiparesis and gait disturbance appeared when she was 22 years old. MRI revealed new lesions at the basal ganglia and subcortical white matter, brain atrophy and diffuse T2 high intensity of cerebral white matter. Cyclophosphamide was effective and there has been no recurrence of symptoms in the last 5 years. We reviewed the non-tumorous LYG/AIL involving the CNS, and discussed the clinical features, MRI imaging and diagnosis of the LYG/AIL.
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PMID:A case of lymphomatoid granulomatosis/angiocentric immunoproliferative lesion with long clinical course and diffuse brain involvement. 1287 57

Blastomycosis was diagnosed in six nondomestic felids from eastern Tennessee, including two Asian lions (Panthera leo persicus), one African lion (Panthera leo), one Siberian tiger (Panthera tigris), one cheetah (Acinonyx jubatus), and one snow leopard (Panthera uncia). Clinical signs included lethargy, anorexia, weight loss, dyspnea, sneezing. ataxia, and paresis. Variable nonspecific changes included leukocytosis, monocytosis, moderate left shift of neutrophils, moderate hypercalcemia, hyperproteinemia, and hyperglobulinemia. Thoracic radiographs revealed interstitial and alveolar changes, consolidation or collapse of a lung lobe, bullae formation, and a pulmonary mass. Agar gel immunodiffusion (AGID) serology for Blastomyces dermatitidis was performed in five felids and was positive in three. The tiger had cerebral blastomycosis and was positive for AGID serologic tests of both cerebrospinal fluid and serum. One percutaneous lung aspirate in the snow leopard and one bronchial aspirate in an Asian lion demonstrated B. dermatitidis organisms. whereas tracheal wash samples and a nasal discharge were nondiagnostic in others. Treatment with itraconazole was attempted in four cats. The tiger improved before euthanasia, whereas the others did not survive beyond initial treatments. In four felids, B. dermatitidis was found in the lungs and tracheobronchial lymph nodes associated with a florid pyogranulomatous reaction; the tiger had a pyogranulomatous encephalomyelitis, and the cheetah had a single pulmonary granuloma. Thoracic radiography, cytologic examination of lung lesion aspirates, and B. dermatitidis AGID serology should be performed on clinically ill zoo felids in endemic areas to rule out blastomycosis.
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PMID:Blastomycosis in nondomestic felids. 1458 83


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