Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2-Deoxy-D-galactose, in a dose of 3 mmol/kg, was administered intraperitoneally twice daily to young rats for periods up to 12 weeks. This dosage schedule resulted in recurrent phosphate trapping predominantly in liver. UTP deficiency was excluded by simultaneous uridine injections. Phosphate trapping was caused by the rapid accumulation of 2-deoxy-D-galactose 1-phosphate and was most pronounced in liver but also demonstrated in small intestine, brain, spleen, and thymus. The marked, although transient, drop in the hepatic content of inorganic phosphate triggered the catabolism of adenine nucleotides and a loss of ATP. Other metabolic pathways affected by phosphate deficiency include glycogenolysis and glycolysis. Increasing with time, repeated doses of the galactose analog led to retardation and arrest of growth, hepatomegaly, and splenomegaly. The average relative liver and spleen weights were elevated 2.5- and 4.5-fold, respectively, after 12 weeks of treatment. Liver damage was indicated by hyperbilirubinaemia and a progressive rise in the activity in plasma of sorbitol dehydrogenase, alkaline phosphatase, and gamma-glutamyltransferase. Examination by light and electron microscopy showed increasing numbers of vacuoles, surrounded by a single membrane, in hepatocytes, sinusoidal endothelial cells, and Kupffer cells. Focal cytoplasmic degeneration in hepatocytes was occasionally indicated by formation of autophagic vacuoles and finger print lysosomes. Hepatocytes of 2-deoxy-D-galactose-treated rats showed a dissociation and fragmentation of the rough endoplasmic reticulum. Sinusoidal endothelial cells and Kupffer cells were markedly enlarged, the latter contained a PAS-positive but amylase resistant substance. Extrahepatic changes included an increased occurrence of vacuolated cells in thymus. Phosphate trapping and its metabolic consequences are common phenomena in the experimental injury induced b 2-deoxy-D-galactose and in some hereditary diseases such as uridylyltransferase deficiency galactosaemia, fructose intolerance and glucose-6-phosphatase deficiency.
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PMID:Consequences of recurrent phosphate trapping induced by repeated injections of 2-deoxy-D-galactose. Biochemical and morphological studies in rats. 4 10

Feeding a high concentration of cotton seed meal to young calves resulted in death with lesions compatible with gossypol toxicity. Calves were fed two different commercially prepared rations. Free gossypol concentrations in different lots of the 17% protein ration varied from 250 to 380 ppm, and the 13% protein ration varied from 40 to 240 ppm. Serum sorbitol dehydrogenase elevation was the most consistent clinical pathological finding. The mean serum sorbitol dehydrogenase concentrations for moribund, hospitalized, and clinically healthy calves were 277, 34, and 45 units/liter. The mean for sorbitol dehydrogenase concentration for healthy calves not fed cotton seed meal was 18 units/liter. Gross lesions included severe effusion of a high protein content fluid into the body cavities of most calves, edema of the mesentery, and hepatomegaly. The most consistent histological lesion was severe centrilobular hepatic necrosis. Elevated levels of liver gossypol were demonstrated. The mean liver gossypol concentration for three calves was 41.7 micrograms/g on a wet weight basis.
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PMID:Pathological and toxicological studies of calves fed a high concentration cotton seed meal diet. 336 92