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)

Neonatal camelids can develop hyperglycemia, hypernatremia, and hyperosmolarity in response to a combination of stress and inadequate water intake. Clinical signs of this syndrome include a fine head tremor, ataxia, and a base-wide stance of the hind limbs, but biochemical analyses are necessary to confirm the diagnosis. Camelids appear to be susceptible to this syndrome because of a poor insulin response to hyperglycemia; hypernatremia results from free water loss associated with glucose diuresis. Water loss associated with glucose diuresis may necessitate a higher rate of fluid administration in camelids with this syndrome than is typically used for treatment of hypernatremia in calves.
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PMID:Hyperglycemia, hypernatremia, and hyperosmolarity in 6 neonatal llamas and alpacas. 1111 Apr 64

Equine granulocytic and monocytic ehrlichiosis caused by Ehrlichia equi and E. risticii, respectively, are seasonal diseases in horses that occur throughout the United States E. equi is transmitted by lxodes ticks and causes high fever, depression, anorexia, limb edema, petechiation, icterus, ataxia, and stiffness in gait. E. risticii, also known as the agent of Potomac horse fever, causes a febrile illness with a colitis of variable severity. Its occurrence is associated with aquatic habitats. The natural route of transmission is oral, through the ingestion of E. risticii infected trematode stages either free in water or in an intermediate host, such as aquatic animals.
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PMID:Ehrlichial diseases. 1121 45

Guajillo (Acacia berlandieri Benth.) is a low-growing, multi-stemmed shrub widely distributed in southern Texas and northern Mexico. Proximate analysis indicates the leaves have high concentrations of nitrogen and energy suggesting that it is a potentially valuable forage resource, yet excessive consumption is believed to cause a hind-limb ataxia. The nutritive value of, and their preference for, guajillo leaves was determined in two trials using male Angora goats (8 months old, 23.7+/-1.09kg initial weight). In a metabolism trial, air-dried guajillo leaves and alfalfa hay were chopped and mixed to prepare four diets containing 0, 25, 50 and 75% of guajillo leaves, which were fed in a 4x4 Latin Square design. Animals were retained in metabolism crates for a 10 day adaptation period followed by a 7 day collection period. Diets were analyzed for DM, OM, N, NDF, ADF, ADF-N, cellulose, lignin, gross energy, phenolic amines, and bovine serum albumin precipitating capacity. Feed DM and OM intake, water consumption, fecal and urine output, nitrogen and energy balance, and urine glucuronic acid output was determined on the animals. Dietary concentration of guajillo had no effect (P>0.05) on intake (26.25+/-1.86g OM kg(-1) BW). Water intake and urine output decreased (P<0.05) with increasing guajillo in the diets, but water retention increased (P<0.05) with increasing guajillo. The digestibility of all the nutrients decreased (P<0.05) with increasing level of guajillo, with ADF digestibility reduced to zero in the 75% guajillo diet. Energy balance and nitrogen balance expressed as percent intake decreased (P<0.05) with increasing level of guajillo. Increasing ADF-N, together with reduced ADF digestibility, reduced the availability of nitrogen in the 75% guajillo diet. Phenolic amine and tannin concentrations increased (P<0.05) as level of guajillo in the diet increased. Glucuronic acid output in goats fed 75% guajillo was significantly (P<0.05) higher than the other diets, and suggests an increased requirement for liver glucose metabolism in goats consuming large amounts of guajillo. In the palatability trial, the same goats were fed 250g of each diet for 9 days in a cafeteria trial to determine the characteristics eliciting a proportional choice among the four diets. Total DMI was similar to the results of the first trial. However, intakes of particular diets decreased (P<0.05) with increasing level of guajillo. Despite an apparently desirable gross energy content of all the diets, those containing guajillo did not meet digestible energy requirements for maintenance and mohair production at moderate levels of activity and production, and although none of the diets appeared to be acutely toxic, the goats preferred the diets lower in guajillo.
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PMID:Nutritive value and palatability of guajillo (Acacia berlandieri) as a component of goat diets. 1129 96

Anorexia is defined as diminished appetite or aversion to food. Clinical manifestations of anorexia have multiple etiologies, which include systemic illness, pain, fever, stress, metabolic disorders, and decreased palatability and learned aversion to food. Disorders of appetite are common in companion and laboratory animal medicine. Anecdotal evidence and personal experience suggest that propofol (2, 6-diisopropylphenol), when given intravenously at subhypnotic doses, causes acute appetite stimulation in dogs. The establishment of a dose-response effect could have important clinical applications; therefore, this study attempts to qualify and quantify the effect of propofol on appetite stimulation in healthy young adult dogs. Six purpose-bred male dogs (age, 6 months) were obtained from a Class A vendor. Dogs were housed individually and provided water ad libitum throughout the study period. All dogs were fed ad libitum to ensure that test conditions and degree of satiety were identical. Each dog was assigned randomly to either an experimental group or control each day of the study. The experimental groups received single bolus intravenous injections of propofol at different dosage levels (0.5, 1.0, 1.5, 2.0, or 3.0 mg/kg of body weight), and the control group received saline. The administrator was blinded to the animals identification and dose. Dosages greater than 3.0 mg/kg resulted in profound sedation and ataxia, which physically inhibited the dogs from obtaining the food; therefore 3.0 mg/kg was the highest dose tested. Dogs were weighed daily to ensure accurate dosing. Dosing was performed at the same time each day to minimize variability. Food intake amounts were recorded at 15, 30, 60, 120, and 1440 min after injection. Food intake was expressed as [food intake (g)/ body weight (kg)/ unit time (min)]. After a 1-w rest period, the study was repeated. Data were analyzed with a type RBF-65 randomized-block factoral design (ANOVA). Each dog served as its own control. The two experiments were analyzed separately, and a P-value of less than 0.05 was used to declare statistical significance. A significant (P, 0.05) increase in food consumption was observed solely during the 0-to-15-min time interval; no significant increase in food consumption was observed at any other time point. This data supports propofols appetite stimulating effect in the initial 15 min after injection. Additional studies are required to explore the mechanism for this effect and to determine whether it occurs in other species.
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PMID:The effect of propofol administered intravenously on appetite stimulation in dogs. 1148 52

Several lines of mice with targeted deletion of the prion protein gene (Prnp) have been produced, some of them appearing phenotypically normal, others developing late-onset ataxia. This has been tentatively attributed to the size of the targeted deletion in the Prnp gene. but a masking role of genetic background could not be excluded. Thus, we have crossed an ataxic mutant line with large deletion of Prnp (Ngsk Prnp0/0) with a knockout line showing only partial deletion of Prnp and no neurological deficits (Zrchl Prnp0/0). A F2 generation was then studied for up to 70 weeks for co-segregation of lesion size and behavioral phenotype, including cognitive and neurological anomalies. These mice were later crossed with a recently generated PrP-deficient line also having a large deletion and late-onset ataxia (Zrch2 Prnp0/0). They underwent similar testing for up to 90 weeks. The ataxic phenotype always co-segregates with large homozygous deletions involving either the Ngsk or the Zrch2 allele, independent of genetic background or sex. Compound heterozygous Zrchl/Ngsk mice or Zrch1/Zrch2 mice showed intermediate neurological phenotypes, suggesting a gene-dosage effect of large deletions. At 12 weeks of age, large deletions were also associated with minor non-cognitive impairments in water maze learning, and hyperactivity in open field and elevated zero maze. These impairments were not predictive for the development of ataxia. Thus, the neurological deficits are closely associated with large deletions, which entail an upregulation of the recently discovered prion Doppel protein (Dpl), while genetic background factors seem to be responsible for shifting the onset of neurological symptoms.
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PMID:Similar target, different effects: late-onset ataxia and spatial learning in prion protein-deficient mouse lines. 1171 97

t-Butyl alcohol is widely used in the manufacture of perfumes and a variety of cosmetics. It is also used as a raw material in the production of isobutylene, which may be used to produce methyl tertiary butyl ether, a common gasoline additive, or to produce butyl elastomers used in the production of automobile tires. The National Cancer Institute nominated t-butyl alcohol to the NTP for study as a result of a review of chemicals found in drinking water. In addition to the high annual production and the potential for occupational exposure, there is also a potential for human exposure to t-butyl alcohol by the inhalation route from its use as an additive in unleaded gasoline. Therefore, toxicity studies of t-butyl alcohol were conducted in male and female F344/N rats and B6C3F1 mice by whole-body inhalation. Animals were evaluated for hematology, clinical chemistry, urinalysis, reproductive toxicity, and histopathology. The genetic toxicity of t-butyl alcohol was assessed by testing the ability of the chemical to induce mutations in various strains of Salmonella typhimurium and L5178Y mouse lymphoma cells or sister chromatid exchanges and chromosomal aberrations in cultured Chinese hamster ovary cells, and by measuring the frequency of micronucleated erythrocytes in rat bone marrow and mouse peripheral blood. In the 18-day inhalation studies, groups of five male and five female rats and mice were exposed to t-butyl alcohol by inhalation at concentrations of 450, 900, 1,750, 3,500, and 7, 000 ppm for 6 hours per day, 5 days per week, for 12 exposure days. All rats and mice exposed to 7,000 ppm were killed moribund following a single 6-hour exposure. One 3,500 ppm male mouse died on day 3. Final mean body weights of 3,500 ppm male and female rats were significantly lower than those of the controls. Final mean body weights and body weight gains of all other exposed groups were similar to those of the controls. In animals exposed to 3.500 ppm, the thymus weights of male and female rats and female mice were less than those of the controls. The liver weights of male and female mice exposed to 3,500 ppm were greater than those of the controls. No grss or microscopic lesion were present in rats or mice. In the 13-week inhalation studies, groups of 10 male and 10 female rats and mice were exposed to t-butyl alcohol at concentrations of 0, 135, 270, 540, 1,080, and 2,100 ppm for 6 hours per day, 5 days per week, for 13 weeks. One 2,100 ppm and five 1,080 ppm male mice died before the end of the studies. The final mean body weight of 2,100 ppm female mice and the mean body weight gains of 1,080 and 2,100 ppm female mice were significantly lower than those of the controls. Clinical findings of toxicity in the 1,080 ppm male mice died during the studies included rough coats and emaciated appearance, hypoactivity, and prostration. Minimal decreases in hematocrit values, hemoglobin concentrations, and erythrocyte counts occurred in the 1,080 and 2,100 ppm male rats at week 13. Hemoglobin concentrations and/or hematocrit values were also minimally decreased in male rats in the lower exposure groups. At week 13, a minimal decrease in urine pH occurred in the 1,080 ppm female and 2,100 ppm male and female rats. Neutrophilia occurred in the 2,100 ppm male mice. Organ weight differences in exposed rats included increased absolute and relative kidney weights of 1,080 ppm males and 2,100 ppm males and females and increased relative liver weights of 1,080 and 2,100 ppm females. There were no treatment-related gross findings in male or female rats or mice; no microscopic lesion occurred in female rats or male or female mice that survived to the end of the study. In male rats, there was an exposure concentration-related increase in the severity of chronic nephropathy. Splenic lymphoid depletion was present in male mice that died during the studies; this lesion was presumed to be secondary to stress. t-butyl alcohol produced no adverse effects on reproductive parameters in male or female rats or mice. The results of all tests of t-butyl alcohol for induction of genetic damage in vitro and in vivo were negative. In vitro, t-butyl alcohol was negative in Salmonella typhimurium and mouse lymphoma cell mutation test, and it did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells. These in vitro studies were conducted with and without metabolic activation (S9). In vivo, no increase in the frequency of micronucleated erythrocytes was observed in peripheral blood samples from mice administered t-butyl alcohol in drinking water for 13 weeks. Also, induction or micronucleated erythrocytes was noted in bone marrow cells of rats administered t-butyl alcohol by intraperitoneal injection. In summary, inhalation exposure of rats and mice to t-butyl alcohol resulted in deaths following a single 7,000 ppm exposure and clinical findings of alcohol toxicity (hyper- and hypoactivity, ataxia) at concentrations of 900 ppm and greater in rats and 1,750 ppm and greater in mice. In 13-week studies at concentrations up to 2,100 ppm, only one death (that of a 2,100 ppm mouse) was attributed to chemical exposure. The most notable evidence of toxicity at the end of 13 weeks was limited to males and consisted of increased kidney weights, which correlated microscopically to increased severity of chronic nephropathy. Reproductive parameters in male and female rats and mice were unaffected after 13 weeks of exposure, and the results of all tests for genetic toxicity were negative.
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PMID:NTP technical report on toxicity studies of t-butyl alcohol (CAS No. 75-65-0). Administered by inhalation to F344/N rats and B6C3F1 mice. 1180 4

Methacrylonitrile is an aliphatic nitrile used extensively in the preparation of homo- and copolymers, elastomers, and plastics and as a chemical intermediate in the preparation of acids, amides, esters, and other nitriles. This aliphatic nitrile is also used as a replacement for acrylonitrile in the manufacture of an acrylonitrile/butadiene/styrene-like polymer. Methacrylonitrile was nominated for toxicity and carcinogenicity testing by the National Cancer Institute due to its high production volume and extensive use, the lack of chronic or carcinogenicity data, and its structural resemblance to the known rat carcinogen acrylonitrile. The current 13-week studies were conducted as part of an overall effort by the NTP to assess the toxicity and carcinogenicity of methacrylonitrile. During the 13-week studies, groups of 20 male and 20 female F344/N rats were administered 0, 7.5, 15, 30, 60, or 120 mg methacrylonitrile/kg body weight in deionized, purified water by gavage. Groups of 20 male and 20 female B6C3F1 mice were administered 0, 0.75, 1.5, 3, 6, or 12 mg/kg methacrylonitrile. Ten male and ten female rats and mice from each group were evaluated on day 32. The results of these studies clearly revealed that male rats are more sensitive than females to methacrylonitrile treatment. In the rat study, 19 males and one female administered 120 mg/kg and two males administered 60 mg/kg died during the first week of the study. Males in the 60 mg/kg group at the 32-day interim evaluation and at 13 weeks and females in the 120 mg/kg group at 13 weeks had significantly lower final mean body weights and body weight gains than did the vehicle controls; the surviving male in the 120 mg/kg group also weighed less than the controls at the 32-day interim evaluation. Clinical findings of toxicity were dose dependent and included lethargy, lacrimation, tremors, convulsions, ataxia, and abnormal breathing. There was hematologic evidence indicating that administration of methacrylonitrile induced minimal, normocytic, normochromic anemia. At the 32-day interim evaluation, a minimal dose-related anemia was evidenced by decreases in hematocrit values, hemoglobin concentrations, and erythrocyte counts in male and female rats. The anemia ameliorated by week 13. Administration of methacrylonitrile resulted in dose-related increases in serum thiocyanate and blood cyanide concentrations of male and female rats. These changes were expected and would be consistent with the in vivo metabolism of methacrylonitrile to cyanide. Blood cyanide concentrations were generally higher in males than in females, which may explain the higher sensitivity of males to the lethal effect of methacrylonitrile. There was also biochemical evidence of increased hepatocellular leakage and/or altered function in dosed male rats, suggesting that the liver may be a target organ for toxic effects of methacrylonitrile. Minimal, but significant, decreases in absolute right kidney and thymus weights (32-day interim evaluation) and increases in liver and stomach weights (week 13) occurred in male rats that received 60 mg/kg compared to the vehicle controls. In female rats, stomach weights of the 60 and 120 mg/kg groups were significantly greater and thymus weights of the 120 mg/kg group were significantly less than those of the controls on day 32 and at week 13; liver weights were also significantly greater in females in the 120 mg/kg group than in the vehicle controls on day 32. Male and female rats administered 60 mg/kg and females administered 120 mg/kg had significantly greater incidences of metaplasia of the nasal olfactory epithelium on day 32 and at the end of the study than did the vehicle controls; incidences of olfactory epithelial necrosis were also significantly greater in females in the 60 and 120 mg/kg groups than in the vehicle controls on day 32. Incidence and/or severity increased with increasing dose in females; however, the mortality in male rats administered 120 mg/kg made it difficult to assess the dose-response relationship in males. The no-observed-adverse-effect level for the nasal cavity of rats was 30 mg/kg. Female rats administered 60 or 120 mg/kg methacrylonitrile had significantly longer estrous cycles than did the vehicle controls. Females in the 60 mg/kg group spent more time in diestrus than the vehicle controls. One male and one female mouse in the 12 mg/kg groups died early. Methacrylonitrile administration caused no significant differences in final mean body weights or body weight gains. Clinical findings included lethargy, tremors, ataxia, convulsions, and abnormal breathing. At the 32-day interim evaluation, stomach weights of males administered 3 mg/kg or greater were significantly greater and thymus weights of males in the 12 mg/kg group were significantly less than those of the vehicle controls. At week 13, however, the stomach weights of only males in the 12 mg/kg group were increased relative to the vehicle controls. No treatment-related histopathologic lesions occurred in mice. Methacrylonitrile did not induce mutations in any of several strains of Salmonella typhimurium, with or without S9 activation, and did not induce sex-linked recessive lethal mutations in germ cells of male Drosophila melanogaster fed methacrylonitrile during the larval stage. Results of in vivo bone marrow micronucleus tests with methacrylonitrile in male rats and mice were also negative. In summary, gavage administration of methacrylonitrile to rats and mice resulted in dose-dependent lethargy, tremors, lacrimation, convulsions, and abnormal breathing. However, these effects were more pronounced in rats than mice; these differences may be attributed to the higher doses of methacrylonitrile administered to rats. Body weight gain and survival data of rats demonstrated that males are more sensitive to methacrylonitrile dosing than females. There is an apparent correlation between blood cyanide concentrations and survival rates, with males having greater cyanide concentrations and lower survival rates than female rats administered methacrylonitrile. Microscopically, the only target of methacrylonitrile toxicity was the olfactory epithelium of the nasal cavity. Necrotic and metaplastic effects were induced in male and female rats that received 60 or 120 mg/kg per day. No similar lesions were observed in mice administered methacrylonitrile. The no-observed-adverse-effect level for olfactory epithelial lesions in male and female rats administered methacrylonitrile for 13 weeks was 30 mg/kg per day. No clear chemical-related effects were observed in male or female mice administered methacrylonitrile for 13 weeks by gavage at doses up to 12 mg/kg per day.
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PMID:NTP technical report on the toxicity studies of methacrylonitrile (CAS No. 126-98-7). Administered by gavage to F344/N rats and B6C3F1 mice. 1180 6

Angelman syndrome is characterized by mental retardation, seizures, ataxia, inappropriate laughter, lack of speech, a particular facial appearance, and generally a chromosome 15q11-q13 deletion. Recently, a fascination with water and water-related activities has been reported in individuals with the syndrome. We report on a 9.6-year-old male previously diagnosed with Angelman syndrome who died unexpectedly by drowning in a shallow backyard wading pool. This case further illustrates the fascination with water by individuals with Angelman syndrome and highlights that this fascination may lead to death. We wish to alert careproviders that this fascination with water and water-related activities may contribute to death and that these individuals should be closely supervised when in the presence of water.
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PMID:Drowning as a cause of death in Angelman syndrome. 1068 6

Niemann-Pick disease type C (NPC) is a fatal, autosomal recessive lipidosis characterized by a unique error in cellular trafficking of cholesterol. In the disease, unesterified cholesterol as well as sphingolipids accumulate in the late endosomes/lysosomes due to mutations in either of two recently isolated genes, NPC1 or NPC2. A metabolic and neurological disorder reminiscent of human NPC disease has been described in Balb/C mice, and it was recently shown that the mutation in the NPC mice resides in the orthologous murine Npc1 gene. Here we have followed the growth rate and applied behavioural methods in order to establish the onset and development of the major symptoms in the NPC mouse model. Wild type and NPC mice were studied during 28-59 days of age. Both male and female NPC mice displayed retarded growth at the age between 25 and 35 days. At the age of 35-45 days the weight was similar to controls and thereafter very rapidly decreased. The battery of coordination tests (vertical screen, beam balancing, coat hanger and rotating rod) established motor impairment of the NPC mice already at the age of 28-42 days, well before the onset of visually detectable ataxia. Decreased exploratory activity and lack of habituation was revealed in the NPC mice by open field test. The diseased mice were unable to learn and remember the location of the hidden escape platform in spatial water maze task suggesting cognitive impairment. In several tests the male NPC mice were more affected than the females. The present study represents the first behavioural analysis of the NPC mice. The battery of behavioural tests employed here should be valuable in the assessment of effective approaches to treat NPC, for which no preventive or curative measures have so far been established.
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PMID:Cognitive deficit and development of motor impairment in a mouse model of Niemann-Pick type C disease. 1185 52

Benzyltrimethylammonium chloride is widely used as a solvent for cellulose, a gelling inhibitor in polyester resins, a chemical intermediate, a paint dispersant, and an acrylic dyeing agent. It is also used in plant growth regulator compositions and synthetic processes. The National Institute of Environmental Health Sciences nominated benzyltrimethylammonium chloride for study due to its high production volume and the potential for occupational exposure, as well as the limited information on toxicity of this chemical. Male and female F344/N rats and B6C3F1 mice received benzyltrimethylammonium chloride by gavage for 16 days or 13 weeks. Animals were evaluated for hematology, clinical chemistry, histopathology, neurotoxicity, and reproductive toxicity. Genetic toxicology studies were conducted in Salmonella typhimurium and in mouse peripheral blood erythrocytes. In the 16-day studies, groups of five male and five female rats received 0, 16, 32, 63, 125, or 250 mg benzyltrimethylammonium chloride/kg body weight in deionized water by gavage, 5 days per week for 16 days. Groups of five male and five female mice received 0, 63, 125, 250, 500, or 1,000 mg/kg benzyltrimethylammonium chloride in deionized water by gavage, 5 days per week for 16 days. All rats in the 125 and 250 mg/kg groups, all mice in the 250, 500, and 1,000 mg/kg groups, and one 125 mg/kg female mouse died on day 1 of the studies. Clinical findings observed in 125 mg/kg male and female rats included abnormal breathing, ataxia, lethargy (males only), nasal and eye discharge, and tremors. Salivation was slightly increased in male and female rats in the 63 mg/kg groups. Female mice in the 125 mg/kg group had a significantly greater absolute liver weight than that of the vehicle controls. No gross or microscopic changes observed in rats or mice were considered related to chemical administration. In the 13-week studies, groups of 10 male and 10 female rats and mice received benzyltrimethylammonium chloride in deionized water by gavage at doses of 0, 12.5, 25, 50, or 100 mg/kg, 5 days per week for 13 weeks. Benzyltrimethylammonium chloride generally had little effect on the body weights of rats or mice. Final mean body weights of dosed animals were within 8% (rats) or 3% (mice) of the control group body weights. The deaths of two female rats and one male and one female mouse administered 100 mg/kg were the result of pharmacologic effects on the cardiovascular system. Some cholinergic effects including chromodacryorrhea, lacrimation, salivation, pupillary constriction, altered gait, and mild tremors were observed at nonlethal doses in rats; these effects were accompanied by alterations in body position. No significant target organ toxicity was observed in dosed rats or mice. Benzyltrimethylammonium chloride was not mutagenic in S. typhimurium strain TA97, TA98, TA100, or TA1535, with or without S9 metabolic activation enzymes. However, significant increases in the frequency of micronucleated normochromatic erythrocytes were found in the peripheral blood of male and female mice administered benzyltrimethylammonium chloride by gavage for 13 weeks. Based on the mortality observed in the 16-day and 13-week studies, rats and mice appeared to be equally sensitive to benzyltrimethylammonium chloride. The minimally toxic dose for rats and mice was estimated to be 50 mg/kg.
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PMID:NTP Toxicity Studies of Benzyltrimethylammonium Chloride (CAS No. 56-93-9) Administered by Gavage to F344/N Rats, Sprague-Dawley Rats, and B6C3F1 Mice. 1198 80


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