Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cimadronate (YM175) is a novel bisphosphonate with potent inhibitory activity on bone resorption under development for the treatment of tumor-induced hypercalcemia, metastatic bone disease and osteoporosis. We conducted intravenous single and repeated dose toxicity studies of cimadronate in beagle dogs. In the single dose study, animals received a single dose of 0.3, 1, 3 or 10 mg/kg of cimadronate and the animals were observed for at least 14 days. At 10 mg/kg, both the male and female dog showed toxic signs such as vomiting, decreased locomotor activities and hypothermia and were killed in extremis within a week after dosing. In the 30-day study, animals received cimadronate at a dosage of 0 (vehicle), 0.03, 0.1, 0.3 or 1 mg/kg/day. At 0.03 mg/kg/day or more, histological findings indicated an increased amount of primary spongiosa in the rib and ilium. At 1 mg/kg/day, degenerative nephropathy, aggregation of spermatozoa and glandular hypoplasia of the prostate gland were observed. On day 16 of dosing one male animal died of acute renal failure. In the 26-week study, animals received cimadronate once weekly at a dosage of 0 (vehicle), 0.31, 0.62, or 1.25 mg/kg. Histopathological examination showed an increased amount of primary spongiosa in the rib at all dosage levels. In addition, similar findings were observed in the lumbar vertebrae at 1.25 mg/kg/week. Histopathological changes in the kidney and male reproductive organs were not observed.
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PMID:Intravenous single and repeated dose toxicity studies of cimadronate (YM175), a novel bisphosphonate, in beagle dogs. 749 Jul 87

An 8-yr-old, captive, female golden lion tamarin ( Leontopithecus rosalia ) with a 6-yr history of hyperbilirubinemia was examined for inappetence and weight loss. Physical examination and blood pressure monitoring under anesthesia revealed hypothermia and hypotension, and blood work revealed hypoglycemia, markedly elevated liver enzymes, including serum alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase, and confirmed the hyperbilirubinemia. A complete blood count suggested chronic lymphoid leukemia. The animal's condition deteriorated during recovery, and the animal died despite aggressive treatment. Grossly, there was micronodular cirrhosis of the liver, severe icterus, and diffuse osteopenia of all examined bones. Microscopic examination of the liver confirmed the micronodular cirrhosis and bone lesions were compatible with diffuse osteopenia and osteomalacia. This brief communication presents a case of chronic liver disease and lesions indicative of metabolic bone disease, also known as hepatic osteodystrophy. To the authors' knowledge, this is the first documented case of hepatic osteodystrophy in the veterinary literature.
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PMID:HEPATIC OSTEODYSTROPHY IN A GOLDEN LION TAMARIN (LEONTOPITHECUS ROSALIA). 2769 75