Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
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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

Monochloroacetic acid, a colorless crystalline material, is used as a postemergence contact herbicide and as an intermediate in the synthesis of other organic compounds. Toxicology and carcinogenicity studies were conducted by administering monochloroacetic acid (99% pure) in deionized water by gavage to groups of F344/N rats and B6C3F1 mice of each sex once daily, 5 days per week for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, mouse lymphoma L5178Y cells, Chinese hamster ovary cells, and Drosophila melanogaster. 16-Day Studies: Groups of five rats of each sex received 0, 7.5, 15, 30, 60, or 120 mg monochloroacetic acid/kg body weight. Doses administered to mice were 0, 15, 30, 60, 120, or 240 mg/kg to groups of five males and 0, 30, 60, 120, 240, or 480 mg/kg to groups of five females. One of five male rats given 120 mg/kg died during the studies. Clear nasal discharge, lacrimation, or both, were observed in all groups of male and female rats receiving monochloroacetic acid. No compound-related gross lesions were observed in rats. All male mice given 240 mg/kg and all females given 240 or 480 mg/kg died during the studies. Hypoactivity, piloerection, ataxia, and lacrimation were observed in mice given 240 or 480 mg/kg. No compound-related gross lesions were observed in mice at necropsy. 13-Week Studies: Groups of 20 rats of each sex received 0, 30, 60, 90, 120, or 150 mg/kg monochloroacetic acid, and groups of 20 mice of each sex received doses of 0, 25, 50, 100, 150, or 200 mg/kg. Three to five animals in each dose group were killed at weeks 4 and 8 for the evaluation of hematology parameters. Compound-related deaths occurred in rats in the three highest dose groups (all males given 120 or 150 mg/kg, 9/10 males given 90 mg/kg, and all females given 90 to 150 mg/kg) and in mice given 200 mg/kg (all males and 2/10 females). Final mean body weights of surviving rats and mice receiving monochloroacetic acid were similar to those of controls. In rats, dose-related increases in blood urea nitrogen, alanine aminotransferase, and aspartate aminotransferase levels were observed, and relative liver and kidney weights were elevated. There were no compound-related changes in the various hematologic or clinical pathology parameters in mice. A dose-related increase in the incidence and severity of cardiomyopathy was observed in male and female rats receiving monochloroacetic acid, and hepatocellular cytoplasmic vacuolization was observed in the high-dose mice that died during the studies. 2-Year Studies: Based on the mortality and compound-related histopathologic lesions observed in the 13-week studies, doses selected for the 2-year studies of monochloroacetic acid were 0, 15, or 30 mg/kg, administered to groups of 70 rats of each sex, and 0, 50, or 100 mg/kg, administered to groups of 60 mice of each sex. Interim evaluations were conducted on 10 rats per dose group after 6 months of treatment with monochloroacetic acid and on seven rats per dose group after 15 months of treatment. Body Weight and Survival in the 2-Year Studies: Mean body weights of low- and high-dose female and low-dose male rats receiving monochloroacetic acid were within 10% of those of controls throughout the studies; however, after week 30, the mean body weights of high-dose male rats were 4% to 8% less than those of controls. In mice, the mean body weights of dosed males were similar to controls, but those of low- and high-dose females were 6% to 10% less than control values after week 52. Survival of high-dose male and dosed female rats and high-dose male mice was significantly lower than that of controls (male rats: control, 27/53; low-dose, 21/53; high-dose, 16/53; female rats: 37/53; 19/53; 26/53; male mice: 46/60; 39/60; 21/60; female mice: 42/60; 40/60; 44/60). Neoplasms and Nonneoplastic Lesions in the 2-Year Studies: There was no compound-related increase in the incidence of neoplasms or nonneoplastic lesions in rats given monochloroacetic acid for 2 years. The incidence of uterine stromal polypss. The incidence of uterine stromal polyps in low- and high-dose female rats was slightly higher than that in controls (2/60; 7/57; 10/60). However, the incidence in the controls was unusually low, and those in the dosed groups were well within the range for NTP historical controls (mean: 21%, range: 10%-38%). Further, because the only malignant stromal neoplasm occurred in a control animal, the polyps were not considered to be related to the administration of monochloroacetic acid. Similarly, there was no monochloroacetic acid-related increase in the incidence of neoplasms in male or female mice, and malignant lymphoma occurred with a significant negative trend in dosed female mice. Increases in the incidence of inflammation of the mucosa of the nasal passages, respiratory epithelial metaplasia of the olfactory epithelium of the nose, and focal squamous cell hyperplasia of the forestomach occurred in dosed male and female mice. Genetic Toxicology: Monochloroacetic acid was not mutagenic in Salmonella typhimurium strains TA100, TA1535, TA1537, or TA98, with or without exogenous metabolic activation (S9). It induced trifluorothymidine resistance in L5178Y cells in the absence of S9 and induced sister chromatid exchanges without S9 in Chinese hamster ovary cells. Monochloroacetic acid did not induce a significant increase in chromosomal aberrations in Chinese hamster ovary cells, with or without S9. Monochloroacetic acid administered in feed was negative for the induction of sex-linked recessive lethal mutations in germ cells of male Drosophila melanogaster; however, when it was administered by injection, the results were equivocal. Conclusions: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity for monochloroacetic acid in male or female F344/N rats given 15 or 30 mg/kg. There was no evidence of carcinogenic activity for monochloroacetic acid in male or female B6C3F1 mice given 50 or 100 mg/kg. Monochloroacetic acid administration was associated with inflammatory lesions of the nasal mucosa, metaplasia of the olfactory epithelium, and squamous cell hyperplasia of the forestomach in male and female mice. Synonyms: Chloroacetic acid, a-chloroacetic acid, chloroethanoic acid
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PMID:NTP Toxicology and Carcinogenesis Studies of Monochloroacetic Acid (CAS No. 79-11-8) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1263 63

Acute extrapyramidal movement disorders have rarely been reported in uremic patients. We had previously presented three cases of acute movement disorders with bilateral basal ganglia lesions in uremia, and had proposed that it is not a rare condition. The objective of this study is to establish a more accurate clinical profile of this rarely described clinical syndrome, and to call attention to its common occurrence. We prospectively studied six patients we encountered from March 1996 to June 2001. We also reviewed the clinical records of a large population of uremic patients and identified six more cases. The clinical manifestations, laboratory findings, neuroimages, and clinical outcomes of these 12 patients were analyzed. When possible, each patient was followed up to the present time. Twelve patients had acute onset of movement disorders and bilateral basal ganglia lesions. All of the patients were diabetic. They had acute-onset Parkinsonism or dyskinesias, together with various symptoms such as consciousness disturbance, dysarthria, dysphagia, or ataxia. The main laboratory test results of abnormalities consisted of elevated blood urea nitrogen, creatinine, and metabolic acidosis. They had uniform neuroimaging findings of symmetrical bilateral basal ganglion changes. These changes regressed or disappeared during follow-up. The clinical prognoses were diverse. We believe that this group of patients represents a well-demarcated clinical syndrome, which is not uncommon but has previously been rarely addressed. The underlying mechanism of such lesions may be associated with metabolic, as well as vascular factors.
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PMID:The syndrome of acute bilateral basal ganglia lesions in diabetic uremic patients. 1292 14

A review of records from the AnTox database of the American Society for the Prevention of Cruelty to Animals Animal Poison Control Center identified 43 dogs that developed increased blood urea nitrogen concentration, serum creatinine concentration, or both as well as clinical signs after ingesting grapes, raisins, or both. Clinical findings, laboratory findings, histopathological findings, treatments performed, and outcome were evaluated. All dogs vomited, and lethargy, anorexia, and diarrhea were other common clinical signs. Decreased urine output, ataxia, or weakness were associated with a negative outcome. High calcium x phosphorus product (Ca x P), hyperphosphatemia, and hypercalcemia were present in 95%, 90%, and 62% of the dogs in which these variables were evaluated. Extremely high initial total calcium concentration, peak total calcium concentration, initial Ca x P, and peak Ca x P were negative prognostic indicators. Proximal renal tubular necrosis was the most consistent finding in dogs for which histopathology was evaluated. Fifty-three percent of the 43 dogs survived, with 15 of these 23 having a complete resolution of clinical signs and azotemia. Although the mechanism of renal injury from grapes and raisins remains unclear, the findings of this study contribute to an understanding of the clinical course of acute renal failure that can occur after ingestion of grapes or raisins in dogs.
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PMID:Acute renal failure in dogs after the ingestion of grapes or raisins: a retrospective evaluation of 43 dogs (1992-2002). 1623 10

The study was conducted to evaluate the effects of xylazine alone (0.05 mg/kg), lignocaine alone (2.0 mg/kg) and a combination of xylazine and lignocaine (0.05 mg/kg and 2.0 mg/kg, respectively) after lumbar epidural administration in water buffalo calves. Fifteen nondescript, male water buffalo calves of 6-8 months of age and weighing between 55 and 75 kg were randomly placed in 3 groups (A, B and C). The agents were administered at the 1st lumbar epidural space. Clinico-physiological parameters such as analgesia, ataxia, sedation, salivation, heart rate, respiratory rate and rectal temperature were studied. Other haematological and biochemical parameters monitored were haemoglobin, packed cell volume, total leukocyte count, plasma glucose, cortisol, protein albumin, globulin, blood urea nitrogen, creatinine, ALT, sodium, potassium and chloride. The onset of analgesia was faster in group C (3.0 +/- 0.44 min) compared with that of group B (4.4 +/- 0.40 min) and group A (34.0 +/- 1.86 min). Analgesia of the thorax, flank, inguinal region, hind limbs, perineum and tail was complete in group C, but mild to moderate in groups A and B. Ataxia was severe in groups B and C and mild in group A. Mild to deep sedation were produced by groups A and C animals. Longer duration and greater depth of analgesia was produced in animals in group C. Heart rate, respiratory rate and rectal temperature decreased in groups A and C. The haematological parameters decreased in all the groups. The biochemical parameters like glucose, cortisol, blood urea nitrogen, creatinine, ALT increased in all the animals. However, total proteins and albumin decreased in the 3 groups. The plasma electrolytes sodium, potassium and chloride did not show any significant change. The results of this study indicated a possible additive analgesic interaction between epidurally administered xylazine and lignocaine, without causing any marked systemic effects in water buffalo calves.
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PMID:Effects of xylazine, lignocaine and their combination for lumber epidural analgesia in water buffalo calves (Bubalus bubalis). 1630 Jan 83

The study was conducted to evaluate the effects of xylazine individually (0.05 mg/kg), ketamine individually (2.5 mg/kg), and a combination of xylazine and ketamine (0.05 mg/kg and 2.5 mg/kg) after lumbar epidural administration in water buffalo calves. Fifteen non-descript, male water buffalo calves of 6-8 months of age weighing between 55 and 75 kg were randomly placed in three groups (groups A, B and C). The agents were administered at the first lumbar epidural space. Clinico-physiological parameters, such as analgesia, ataxia, sedation, salivation, heart rate, respiratory rate and rectal temperature were studied. Other haematological and biochemical parameters monitored were haemoglobin, packed cell volume, total leukocyte count, plasma glucose, cortisol, protein albumin, globulin, blood urea nitrogen (BUN), creatinine, alanineamino transferase (ALT), sodium, potassium and chloride. The onset of analgesia (mean +/- SEM) was faster in group C (3.2 +/- 0.20 min) compared with that of group B (4.6 +/- 0.22 min) and group A (34.0 +/- 1.86 min). Analgesia of the thorax, flank, inguinal region, hind limbs, perineum and tail was complete in group C, but mild to moderate in groups A and B. Ataxia was severe in group C and mild in groups A and B. Mild to deep sedation was produced by groups A and C animals. Group B animals failed to produce sedation. Longer duration and greater depth of analgesia was produced in animals of group C. Heart rate, respiratory rate and rectal temperature decreased in groups A and C. The haematological parameters decreased in all the groups. The biochemical parameters like glucose, cortisol, BUN, creatinine, and ALT increased in all the animals. However, total proteins and albumin decreased in the three groups. The plasma electrolytes sodium, potassium and chloride did not show any significant change. The results of this study indicated a possible synergistic analgesic interaction between epidurally administered xylazine and ketamine, without causing any marked systemic effects in water buffalo calves.
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PMID:Xylazine, ketamine and their combination for lumbar epidural analgesia in water buffalo calves (Bubalus bubalis). 1697 Jun 33

Late-onset urea cycle disorder in a 20-month-old boy is unusually associated with Klinefelter syndrome with a 47XXY karyotype. We record the typical clinical and biochemical findings of ornithine transcarbamylase (OTC) deficiency in a young boy with a short history of recurrent vomiting, self mutilating behaviour, lethargy, ataxia and seizures. Laboratory studies showed hyperammonaemia and orotic aciduria, with normal citrulline and other urea cycle amino acids. Unfortunately, a liver biopsy for OTC activity measurement was refused by the parents. A rapid reversal of phenotype was seen on the introduction of a low-protein diet with accompanying benzoate and phenylbutyrate administration. Linkage studies suggested the inheritance of two X chromosomes, which was confirmed by karyotype analysis. Sequencing of all exons and immediate splice site regions revealed no sequence alterations in these sections of the OTC gene. A search for skewing of X-inactivation in the liver was not possible but we did show a random pattern of X-inactivation in leukocytes. The possibility of maternal X chromosome iso-disomy in our patient was discounted by microsatellite analysis, which revealed the inheritance of two independent X chromosomes. Mutation analysis in the OTC gene has shown that approximately 20% of patients with liver biopsy confirmed OTC deficiency do not have mutations in the coding or immediate splice-site sequences of this gene. Their classification as OTC phenocopies remains speculative, awaiting clarification of the underlying DNA alteration. We report on the novel association of OTC deficiency and Klinefelter syndrome with the additional interest of a probable unusual genetic defect underlying the OTC abnormality.
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PMID:An OTC deficiency 'phenocopy' in association with Klinefelter syndrome. 1718 14

Xylazine-ketamine combination was evaluated for its efficacy and safety after epidural administration in uraemic and healthy goats. The combination (xylazine 0.025 mg/kg and ketamine 2.5 mg/kg) was administered to uraemic (n = 6) and healthy (n = 6) animals in the lumbosacral epidural space. The combination was evaluated in terms of clinical, physiological, haematological and biochemical parameters. The onset of analgesia was faster in healthy animals than in uraemic animals. Xylazine and ketamine produced complete analgesia of tail, perineum, inguinal and thigh regions in all animals of both groups. However, healthy animals showed longer duration of complete analgesia than did uraemic animals. Greater ataxia was recorded in healthy animals than in uraemic animals. The heart rate showed a significant decrease in both groups; however, respiratory rate and rectal temperature did not show any significant changes. Haemoglobin, packed cell volume and total leukocyte count decreased non-significantly in both groups. Total leukocyte count was significantly higher in uraemic animals. A significantly higher value of urea nitrogen and creatinine was recorded in uraemic animals. The blood electrolytes (Na+, K+ and Cl-) and blood gases (PO2 and PCO2) did not show any significant changes in both groups; however, base excess was significantly higher in uraemic animals. The effects produced by the combination on different systems were transient and values normal as the effect of the drugs wore off. The results suggest that the combination when used epidurally in uraemic goats produced effective and safe surgical analgesia.
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PMID:Effects of epidural ketamine-xylazine combination on the clinicophysiological and haematobiochemical parameters of uraemic and healthy goats. 1721 18

The study was conducted in 9 healthy adult goats of either sex, weighing 15-20 kg, to evaluate and compare the clinicophysiological effects of spinally administered ketamine alone and in combination with xylazine and medetomidine. Nine trials each of the three treatments were conducted randomly by injecting ketamine (2.5 mg/kg) (n = 9), ketamine and xylazine (2.5 mg/kg and 0.05 mg/kg) (n = 9) and ketamine and medetomidine (2.5 mg/kg and 10 microg/kg) (n = 9). The drugs were administered at the lumbosacral subarachnoid space under strict aseptic conditions. The treatments were evaluated on the basis of clinicophysiological, haematological, biochemical and haemodynamic observations. Ketamine produced mild to moderate analgesia of the hindquarters. Its combination with either xylazine or medetomidine produced complete analgesia of the hindquarters for 45-60 min. Ataxia was moderate in the ketamine group, whereas animals attained sternal recumbency in the combination groups. A moderate degree of sedation was recorded in the combination groups. Heart rate and respiratory rate depression in the combination groups and heart rate and respiratory rate stimulation in ketamine group were recorded. Haematological parameters decreased in all the groups. Increase in serum glucose, creatinine and urea nitrogen was recorded in all the groups. Serum electrolytes did not show any significant change. The results showed that the combination of ketamine with xylazine or medetomidine at these dose rates produced a comparable degrees of analgesia of hindquarters with transient and minimal cardiopulmonary side effects.
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PMID:Clinicophysiological effects of spinally administered ketamine and its combination with xylazine and medetomidine in healthy goats. 1729 60

Four laboratory studies were conducted in Beagle dogs to evaluate the safety of a novel ectoparasiticide combination of metaflumizone plus amitraz (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) when applied according to the recommended dosage of >/=20mgmetaflumizonekg(-1) plus >/=20mgamitrazkg(-1), at exaggerated and repeated dosages, and if accidentally orally ingested. Parameters evaluated included body weight, food consumption, clinical, physical and neurological examinations, clinical pathology and gross and microscopic pathology. Exaggerated and repeated topical treatment with metaflumizone plus amitraz administered at 1x, 3x and 5x the recommended dose had no effect on clinical findings, heart rates, body weight, food consumption, physical/neurological examinations, macroscopic and microscopic pathology. Very slight, transient, clinically insignificant increases in serum urea nitrogen were noted in some dogs treated at all dose rates tested. This effect was not persistent, was not dose-responsive, nor aggravated by repeated applications and was not associated with a corresponding increase in creatinine or renal pathology. Therefore, these increases in urea nitrogen were suspected to be of non-renal origin and were not considered toxicologically significant. Exaggerated doses (3x and 5x) caused very mild, transient hyperglycemia, most notably in some adult females. Transient and inconsistently noted mild increases in leukocytes, neutrophils and monocytes were observed in some 3x and 5x treated dogs at some intervals. None of the effects noted were aggravated by repeated administration. When 10% of the recommended topical dose was orally administered to mimic exposure due to licking the application, avoidance behaviors including spitting, head shaking, and salivation were noted immediately in all animals. Consequently, voluntary oral ingestion is considered unlikely. Transient decreased activity, slightly reduced body temperature and pale oral mucous membranes were noted in some animals beginning 1-2h posttreatment. Ataxia, resolving within 4h posttreatment, was noted in one female. Oral administration had no effect on clinical pathology. Results from these four studies indicate repeated use of metaflumizone plus amitraz causes no adverse health effects when used as recommended in dogs as young as 8 weeks of age.
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PMID:Safety of a topically applied spot-on formulation of metaflumizone plus amitraz for flea and tick control in dogs. 1792 49


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