Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been proposed that hepatic encephalopathy and malnutrition in cirrhosis can be reversed by infusion of a protein formula (F080) enriched with branched-chain amino acids (valine, leucine, isoleucine) and containing decreased amounts of aromatic amino acids (phenylalanine, tyrosine, tryptophan). This hypothesis was tested by measuring changes in encephalopathy status, plasma ammonia, amino acid profile, and liver function during seven metabolic balance studies in three patients with cirrhosis and subclinical encephalopathy given increasing amounts (20-100 g/d) of F080. The results showed the following: 1) positive nitrogen balance was achieved only with 80 and 100 g F080/day; 2) plasma ammonia fell during negative, but increased during positive nitrogen balance; 3) plasma tyrosine and cystine fell significantly (p less than 0.05) with all intakes of F080; 4) the abnormal branched-chain to aromatic amino acid ratio was reversed; 5) extracellular volume was expanded in all patients; 6) albumin, bilirubin, prothrombin time became abnormal; and 7) encephalopathy did not significantly change from baseline. It is concluded that, in this population, F080 is an inadequate nutritional formula when given as the sole protein source because it produces hypotyrosinemia and hypocystinemia. The marked changes in the ratio of branched-chain to aromatic amino acids are not accompanied by improvement in encephalopathy.
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PMID:Total parenteral nutrition with F080 in cirrhotics with subclinical encephalopathy. 640 94

In order to determine whether non-specific defects of protein synthesis account for reduced levels of cytochrome P-450 in cirrhotic liver, total microsomal protein synthesis and response to microsomal enzyme-inducing agents have been examined in rats. Cirrhosis was produced by administration of carbon tetrachloride (CCl4) and phenobarbitone for 10 weeks. Ten days after stopping these agents, cytochrome P-450 levels were 30% lower in cirrhotic liver than in controls (p less than 0.0001). However, total microsomal protein synthesis, determined in vivo by administration of [3H]-leucine, was similar in cirrhotic (1347 +/- 420 dpm/mg protein) and control (1317 +/- 303 dpm/mg protein) liver. Three separate types of microsomal enzyme-inducing agents, phenobarbitone, beta-naphthoflavone, and pregnenolone 16 alpha-carbonitrile, were administered to cirrhotic and normal rats. In both groups of animals increases of total cytochrome P-450 and selective changes of cytochrome P-450 isoenzymes (assessed by mixed function oxidase activity towards four substrates) were qualitatively and quantitatively similar. It is concluded that hepatocytes of cirrhotic rat liver synthesize microsomal protein at a normal rate but less of it is cytochrome P-450, and the entire process of enzyme induction is intact. Thus, it appears likely that altered regulation of basal levels of cytochrome P-450 rather than an altered response of the liver is responsible for the lowered cytochrome P-450 content of cirrhotic rat liver.
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PMID:Microsomal protein synthesis and induction of cytochrome P-450 in cirrhotic rat liver. 649 79

Infusion of a mixture of branched-chain 1-amino acids (BCAA; isoleucine, leucine, and valine) in six male patients suffering from hepatic cirrhosis led to an increase in serum GH, while serum PRL was not affected. In the same patients arginine infusion stimulated GH and PRL release. These findings demonstrate that hypothalamo-pituitary responsiveness to amino acid stimulation is preserved in cirrhosis and that administration of these amino acids has some endocrine effect.
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PMID:Changes in pituitary secretion after administration of branched-chain amino acids to patients with hepatic cirrhosis. 666 75

Valine (62.5 mg per kg), leucine (70 mg per kg) and equal amounts of the calcium salts of the corresponding keto acids, i.e., alpha-ketoisovaleric acid (KIVA) and alpha-ketoisocaproic acid (KICA) were orally administered to patients with cirrhosis and to control subjects. Valine or leucine ingestion increased serum valine and leucine levels and the corresponding keto acids, KIVA and KICA, in cirrhotics and controls. KIVA or KICA ingestion increased serum KIVA and KICA concentrations within a few minutes associated with a rise in valine and leucine. In cirrhotics, administration of valine or KIVA resulted in significantly higher serum valine or KIVA concentrations than in control subjects. The clearance of valine and KIVA from blood was also delayed in cirrhotic patients. No such differences were observed after leucine or KICA ingestion. It is suggested that cirrhotics have a diminished tolerance for valine. Since the tolerance for KIVA, but not KICA, is also impaired, it appears that cirrhotics have a derangement in one or more metabolic steps distal to the branched-chain keto acid dehydrogenase.
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PMID:Evidence for valine intolerance in patients with cirrhosis. 674 55

The amino acid solution, Aminofusin hepar, was evaluated for treatment of hepatic encephalopathy and for parenteral nutrition of patients with liver cirrhosis in correlation to changes in amino acid levels. In contrast to amino acid solutions used for the parenteral nutrition of patients without liver disease, this solution contains an increased proportion of branch chained amino acids and of arginine and ornithine, and a reduced proportion of phenylalanine, methionine, glycine and threonine. The changes in the plasma amino acid levels after infusion of this solution were measured in 4 cirrhotics. The concentration of leucine, isoleucine, valine, ornithine and arginine increased markedly, whereas phenylalanine, methionine, tyrosine, glycine and threonine decreased. The ammonia level in venous blood increased slightly. 4 cirrhotics with encephalopathy were treated for 7 days. In 3 of them the neuropsychiatric symptoms were completely reversed, whereas in the remaining 1 no clinical improvement was achieved in spite of normalization of the plasma aminogramm. In this patient a constant rise of blood ammonia was noted. The indications for special amino acid solutions in liver diseases are discussed.
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PMID:[Parenteral feeding of patients with liver cirrhosis with hepatic encephalopathy]. 677 52

Hepatic-Aid is purported to ameliorate encephalopathy and promote positive nitrogen balance in protein-intolerant, cirrhotic patients by correcting their imbalanced amino acid profile. This study evaluated Hepatic-Acid by comparing a 50-g Casein diet with an identical diet with 20-g Casein/30-g Hepatic-Aid per day in a cross-over study. Four patients with biopsy-proven stable cirrhosis, encephalopathy, and under-nutrition were studied. Each study period included three days of equilibration and eight days of metabolic balance, with the following measured at baseline and on balance days 5 and 8: routine biochemistry, fasting ammonia, psychometric tests, EEG, and plasma amino acid profiles. There was no significant change in clinical status, routine biochemistry, fasting ammonia, psychometrics or EEG between the two study periods. Mean (+/-SD) nitrogen balance on the Casein diet at 1.5 +/- 1.5 g/day was not significantly different from that on the Hepatic-Aid diet at 1.5 +/- 1.2 g/day. Plasma amino acid profiles showed a significant fall (p less than 0.05) in fasting and intraprandial tyrosine (tyr) and phenylalanine (phe) on Hepatic-Aid, but only intraprandial leucine (leu), isoleucine (ile), and valine (val) were significantly increased (p less than 0.05) on Hepatic-Aid. The ratio leu + ile + val to tyr + phe was significantly increased (p less than 0.05) on Hepatic-Aid. It is concluded that Hepatic-Aid, as given in this study, maintains N balance similar to Casein, alters the amino acid profile towards normal, but does not ameliorate encephalopathy.
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PMID:Comparison of the effects of Hepatic-Aid and a Casein modular diet on encephalopathy, plasma amino acids, and nitrogen balance in cirrhotic patients. 683 Mar 37

To elucidate the relative contribution of parenchymal liver damage and spontaneous portal-systemic shunting to the reduction of peripheral insulin degradation rate and the decrease in plasma concentrations of three branched chain amino acids (valine, leucine, and isoleucine), plasma insulin, C-peptide, and amino acid concentrations were measured during oral glucose tolerance tests in 17 patients with liver cirrhosis, 10 with idiopathic portal hypertension, 5 hospitalized controls, and normal subjects. None of the patients had evidence of hepatic encephalopathy. Patients with idiopathic portal hypertension had histologically minimum hepatic fibrosis in spite of the existence of extensive exophageal varices. The molar ratio between plasma concentrations of C-peptide and insulin was significantly decreased in patients with cirrhosis, but not in those with idiopathic portal hypertension. In both patients with cirrhosis and idiopathic portal hypertension, the three branched chain amino acid levels were significantly decreased and the molar ratio between the concentrations of the three branched chain amino acids and two aromatic amino acids (tyrosine and phenylalanine) were markedly reduced. These results suggest that spontaneous portal-systemic shunting does not primarily contribute to the reduced degradation of insulin, but has a close relationship with the decrease in branched chain amino acid levels and in the molar ratio of plasma amino acids. In addition, the present data indicate that decreased branched chain amino acid levels in patients with cirrhosis is not merely ascribed to hyperinsulinemia and that the decrease in the molar ratio of plasma amino acids is not specific to the presence of hepatic encephalopathy.
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PMID:Effect of spontaneous portal-systemic shunting on plasma insulin and amino acid concentrations. 698 17

1. Intravenous infusions of L-valine (600 mumol/min), L-isoleucine (150 mumol/min), L-leucine (300 mumol/min) and a mixture of the three branched-chain amino acids (70% L-leucine, 20% L-valine, 10% L-isoleucine; 270 mumol/min) were given to four groups of healthy volunteer subjects. Whole-blood concentrations of amino acids and glucose and serum insulin were measured before and during the infusions. 2. Valine and isoleucine infusions resulted in twelve- and six-fold increases in the respective amino acid. During valine infusion, tyrosine was the only amino acid for which a decrease in concentration was seen (25%, P less than 0.05). With isoleucine administration, no significant changes were found. In contrast, leucine infusion (during which the leucine concentration rose about sixfold) was accompanied by significant decreases in tyrosine (35%), phenylalanine (35%), methionine (50%), valine (40%) and isoleucine (55%). The arterial glucose concentration fell slightly (5%) and the insulin concentration increased 20% during leucine infusion. 3. Infusion of the mixture of the three branched-chain amino acids resulted in marked decreases in tyrosine (50%), phenylalanine (50%) and methionine (35%). The decreased amino acid levels remained low for 2 h after the end of the infusion. 4. The present findings demonstrate that intravenous infusion of leucine (not infusion of valine or isoleucine) results in marked reductions in the concentrations of the aromatic amino acids and methionine. Infusion of a mixture of the three branched-chain amino acids gives results similar to those obtained with leucine infusion alone. Thus a mixed branched-chain amino acid solution with leucine as its main constituent seems to be the best alternative in the treatment of patients with hepatic cirrhosis and encephalopathy.
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PMID:A comparison of the effects of intravenous infusion of individual branched-chain amino acids on blood amino acid levels in man. 701 2

1. The metabolic effect of alpha-oxoisocaproate (4-methyl-2-oxovalerate) infusion was examined in six patients with cirrhosis and in nine healthy control subjects. The arterial concentrations of amino acids, urea, ammonia, insulin and catecholamines were determined in the basal state and during intravenous infusion of alpha-oxoisocaproate (300 mumol/min) for 150 min. The exchanges of amino acids and substrates across the splanchnic region, the brain and the leg were examined in the healthy subjects by a catheter technique. 2. Basal alpha-oxoisocaproate levels were similar in patients and control subjects. During infusion the concentrations of alpha-oxoisocaproate rose to 90-130 mumol/l; they were 20-35% lower in the patients. Arterial leucine concentration increased in both groups to 250-300 mumol/l. Valine and isoleucine concentraions decreased (50-60%) as did to a lesser extent the concentrations of aromatic amino acids and methionine. 3. Regional exchange of amino acids was not significantly influenced by alpha-oxoisocaproate infusion. Arterial urea concentration decreased (12%, P less than 0.05) and ammonia levels rose (15-25%, P less than 0.05) in both groups. In the patients both adrenaline (100%, P less than 0.001) and noradrenaline concentrations were elevated (350%, P less than 0.001) in the basal state; insulin levels were similar to those in control subjects. 4. It is concluded that alpha-oxoisocaproate is rapidly transaminated to leucine in patients with cirrhosis and in healthy control subjects. alpha-Oxoisocaproate infusion resembles leucine infusion in its influence on aromatic amino acid concentrations, but in addition it elicits increased ammonia levels and decreased urea formation.
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PMID:Intravenous infusion of alpha-oxoisocaproate: influence on amino acid and nitrogen metabolism in patients with liver cirrhosis. 706 Mar 35

Hepatic encephalopathy in patients with severe liver disease was associated with marked elevation of either serum methionine or blood ammonia levels or with simultaneous moderate increases in both parameters. CSF methionine levels also increased in encephalopathic patients with fulminant hepatitis and liver cirrhosis. Increased influx of methionine into the brain over the theoretical values predicted from Pardridge's equation suggested that accelerated transport of serum methionine across the blood-brain barrier was observed in these cases with hepatic encephalopathy. Hepatic encephalopathy in acute carbon tetrachloride liver injury could be obtained experimentally following intraperitoneal injection of ammonium acetate in rats, which already received intragastric administration of methionine. However, similar encephalopathy could not be observed by the administration of glycine or leucine in place of methionine. These results suggest at least that methionine and ammonia act synergistically on inducing hepatic encephalopathy.
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PMID:Impaired metabolism of methionine in severe liver diseases. II. Clinical and experimental studies on role of impaired methionine metabolism in pathogenesis of hepatic encephalopathy. 710 99


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