Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Single dose toxicity studies of T-3761 were carried out in mice, rats and dogs, and the following results were obtained. 1. The approximate lethal dose of T-3761 were more than 5,000 mg/kg for mice and rats, more than 2,000 mg/kg for dogs with oral administration, and more than 5,000 mg/kg for mice and rats with subcutaneous injection. LD50 values with intravenous injection were 783 mg/kg for male mice, 832 mg/kg for female mice, 341 mg/kg for male rats, and 403 mg/kg for female rats. Two dogs given 200 mg/kg did not die but one of the two treated with 400 mg/kg died after intravenous injection. The approximate lethal dose for dog was 400 mg/kg. 2. Neither abnormal symptoms and macroscopic findings nor deaths were observed in mice and rats treated orally. Granuloma around precipitates of T-3761 at the injection site was seen in mice and rats injected subcutaneously. Slight increase of white blood cell count, serum GOT, CPK and urea nitrogen were transiently found in dogs treated orally. Neither abnormal macroscopic findings nor deaths were observed in dogs treated orally. 3. Decreased motor activity and irregular breathing were observed in mice and rats injected intravenously. In dying animals, tonic or clonic convulsions were observed. Vomiting, hyperemia of ophthalmic mucosa, edema of face, decrease of motor activity, salivation and decrease in body temperature were observed in dogs injected intravenously. At higher doses, scream and tachypnea were observed while injecting. Hematological examinations disclosed that increases in red blood cell count, white blood cell count, hematocrit and hemoglobin were found transiently. In biochemical examinations, increases in serum GOT, GPT, urea nitrogen and creatinine were found transiently. One dog intravenously injected 400 mg/kg, showed tonic convulsion and died.
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PMID:[Single administration toxicity studies of T-3761 in mice, rats and dogs]. 766 80

A combination of unexplained peripheral neuropathy, hypoparathyroidism, and the inability to cope with metabolic stress could point to a rare inborn error of metabolism, such as mitochondrial trifunctional protein (MTP) deficiency.Here, we describe a 20-year-old woman who was known since childhood with axonal motor sensory polyneuropathy of unknown origin. She presented with progressive dyspnoea, and increased muscle weakness, preceded by 6 days of fever, vomiting, and diarrhoea. Laboratory testing showed rhabdomyolysis, and hypocalcaemia with low parathyroid levels. The patient was intubated because of respiratory insufficiency and a viral and bacterial pneumonia was diagnosed. She was discharged after 16 days of admission. Metabolic screening, performed at the time of rhabdomyolysis, showed increased concentrations of long-chain 3-hydroxyacyl carnitine species, together with elevated urinary excretion of 3-hydroxy dicarboxylic acids. Decreased activity of long-chain 3-hydroxyacyl-CoA dehydrogenase and long-chain 3-ketoacyl-CoA thiolase in peripheral lymphocytes and fibroblasts confirmed a MTP deficiency. Sequence analysis of the HADHB gene showed two heterozygous variants: c.209+1G>C (splicing defect) and c.980T>C (p.Leu327Leu). When the acylcarnitine profile was repeated after the episode of rhabdomyolysis had resolved it showed no abnormalities.Our case illustrates a cluster of peripheral neuropathy, episodic rhabdomyolysis, and hypoparathyroidism in a patient with MTP deficiency caused by mutations in the HADHB gene. It stresses the importance of performing metabolic screening when patients are most symptomatic, as normal results can be found at times when no metabolic stress is present. Screening is relatively easy and timely diagnosis has important implications for treatment.
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PMID:Peripheral Neuropathy, Episodic Rhabdomyolysis, and Hypoparathyroidism in a Patient with Mitochondrial Trifunctional Protein Deficiency. 2868 93