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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A protein-free diet causes a paradoxical increase of blood ammonia levels that seems to be due to decreased liver content of acetylglutamate, the physiological activator of carbamylphosphate synthetase. The purpose of this study was to assess whether oral administration to rats of carbamylglutamate, a metabolically stable activator of carbamylphosphate synthetase, could decrease the blood ammonia levels increased by the protein-free diet. We show that ingestion of moderate doses of carbamylglutamate increased about sixfold the liver content of carbamylphosphate synthetase activators and restores to normal values the blood ammonia levels. Excess ammonia is eliminated in urine as urea. These results indicate that carbamylglutamate, which is not toxic, could be useful in the treatment of hyperammonemia, especially in cirrhosis.
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PMID:Treatment of hyperammonemia with carbamylglutamate in rats. 154 25

Despite a marked reduction of the urea cycle capacity, patients with well-compensated chronic liver disease excrete near-normal amounts of urea. Compensation of the urea cycle defect apparently occurs through the activation of liver glutaminase, as suggested by an inverse relationship between the in vitro ureagenic capacity and the flux through glutaminase in liver tissue from patients with a normal, fatty, or cirrhotic liver. In these patients, the flux through glutaminase, as determined in vitro, increases in parallel with the plasma bicarbonate level and plasma pH determined in vivo. In view of this and results from previous studies, the following hypothesis is suggested: The decrease of urea cycle enzyme activities in liver cirrhosis produces metabolic alkalosis due to an impaired bicarbonate elimination. Alkalosis in turn activates and stabilizes hepatic glutaminase and accordingly mitochondrial ammonia provision for carbamoylphosphate synthetase. This results in a compensatory stimulation of the urea cycle flux in the cirrhotic patient to near-normal rates, despite the marked reduction of urea cycle enzyme activity. Accordingly, alkalosis is an important driving force for urea synthesis in the cirrhotic patient. With respect to clinical medicine, attention must be paid to acid-base disturbances in the hyperammonemic patient.
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PMID:Metabolic alkalosis as driving force for urea synthesis in liver disease: pathogenetic model and therapeutic implications. 160 Mar 51

Structural sequelae of inherited defects of the urea cycle in general, and their liver pathology in particular, are still not well understood. This holds true especially for the possible late effects in involved organs of patients now surviving longer because of more effective therapy. Some urea cycle defects may result in chronic and progressive liver damage, as has been reported. A peculiar type of liver fibrosis was observed in a girl with carbamoylphosphate synthetase deficiency, who survived for 1 year and 7 months. Hepatic fibrosis, or even cirrhosis, has been observed in argininosuccinic aciduria. Long-term survivors with urea cycle disorders may form a group at risk for the development of chronic fibrosing liver disease.
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PMID:Liver fibrosis in carbamoylphosphate synthetase deficiency. 365 42

Hepatomegaly is an important clinical finding in patients with argininosuccinic aciduria (a hereditary defect of the urea cycle enzyme, argininosuccinate lyase [argininosuccinase]). A severe degree of liver fibrosis, almost corresponding to cirrhosis, was observed in liver biopsy material obtained from a boy with this disorder. This observation is of interest in light of the fact that liver fibrosis or cirrhosis are hallmarks of many inheritable phenotypes, and especially of inborn errors of metabolism. Variable degrees of liver fibrosis are noted in other inborn defects of the urea cycle, eg, in ornithine transcarbamylase and carbamoylphosphate synthetase deficiencies. These findings appear to indicate that inheritable defects of urea synthesis may form a group of metabolic disorders prone to cause hepatic fibrosis, or even cirrhosis, as shown in our patient.
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PMID:Severe liver fibrosis in argininosuccinic aciduria. 375 45

Cirrhosis induced in rats by carbon tetrachloride was used to study alterations in the activities and lobular distribution of carbamoylphosphate synthetase and glutamine synthetase. Specific activity of carbamoylphosphate synthetase in cirrhotic subjects was decreased to 70% of controls. Staining was homogeneous within micronodular areas, but varied from area to area and generally showed a decreased intensity. Specific activity of glutamine synthetase and the size of the glutamine synthetase-positive area were decreased to 20% and less of controls. Glutamine synthetase-positive hepatocytes were rare and scattered at the periphery of nodular areas and within fibrous septa, the normal association with the central veins being widely lost. Rarely, complete micronodules showed a slight homogeneous staining for glutamine synthetase. Arginase activity was not affected, whereas glutaminase activity was enhanced by 50%. Serum levels of ammonia were elevated more than 2-fold and those of glutamine by 30%. In contrast, urea levels tended to be slightly diminished. Serum ammonia levels showed a clear negative correlation with the specific activity of glutamine synthetase and the size of the glutamine synthetase-positive area. Furthermore, blood urea levels correlated with the sum of ammonia and glutamine concentrations, but not with each of these substrate concentrations alone. These data suggest that the changes in activity and distribution of glutamine synthetase contribute to hyperammonemia in cirrhosis. Despite a reduced activity of the initial enzyme of the urea cycle, urea synthesis is not diminished accordingly. This may be due to an enhanced flux caused by the elevated blood level of ammonia and an increased hydrolysis of glutamine, because of higher levels of glutaminase.
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PMID:Changes in distribution and activity of glutamine synthetase in carbon tetrachloride-induced cirrhosis in the rat: potential role in hyperammonemia. 791 4