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)

Previous uncontrolled studies indicated a positive effect of keto analogs of amino acids on plasma ammonia in patients with cirrhosis of the liver and on portal-systemic encephalopathy. In the present double-blind study the influence of keto analogs of the branched chain amino acids valine, leucine and isoleucine on plasma ammonia and encephalopathy was investigated in 12 patients with cirrhosis of the liver and surgical portal systemic shunts. In addition to the usual therapy with lactulose and protein restriction (40 g protein/day) all patients received 15.24 g keto analogs and placebo orally over 4 weeks in a crossover regimen. In contrast to uncontrolled studies, plasma ammonia, which was elevated in all patients before the beginning of the study, was not significantly changed. In addition plasma amino acids, electroencephalogram, number connection test, clinical state and laboratory tests were not influenced by the therapy with keto analogs.
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PMID:Oral keto analogs of branched-chain amino acids in hyperammonemia in patients with cirrhosis of the liver. A double-blind crossover study. 712 54

Femoral arterio-venous (A-V) differences of blood free amino acids and plasma ammonia (NH3) were simultaneously determined after an overnight fast in 16 patients with decompensated liver cirrhosis in the absence and presence of encephalopathy, as compared with those in 8 control subjects. In spite of increased releases of phenylalanine (Phe) and tyrosine (Tyr) from the peripheral tissue, releases of isoleucine (Ile) and leucine (Leu) as well as alanine (Ala) were found to be significantly reduced in decompensated liver cirrhosis, particularly in the presence of hepatic encephalopathy. Furthermore, NH3 was found to be significantly taken up by the skeletal muscle of these patients, and a positive correlation was observed between arterial NH3 level and the A-V differences of Leu, of Ile and of Ala. These findings strongly suggest that net degradation (or utilization) of branched-chain amino acids (in particular, Leu and Ile) is enhanced in the muscle for detoxication of ammonia (i.e., glutamine synthesis) by supplying the carbon skeleton and energy in cirrhosis of the liver.
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PMID:Augmented utilization of branched-chain amino acids by skeletal muscle in decompensated liver cirrhosis in special relation to ammonia detoxication. 722 60

1. To investigate the effects of starvation, elective surgery, accidental injury and other clinical conditions on the metabolism of branched-chain amino acids in man, we have measured the basal concentration of leucine and the removal of metabolic effects of infused L-leucine. 2. The blood concentration of leucine as significantly increased by surgery, starvation and accidental injury, and decreased in cirrhosis. It tended to increase in diabetes and was unaffected by muscular dystrophy. 3. The half-life of infused leucine was nearly doubled by 4 days of complete starvation, unaltered by surgery and decreased by severe accidental injury, Infusion with Intralipid, which increased free fatty acid and ketone-body concentrations, had no effect on the removal of a leucine load. The clearance rate of infused leucine was reduced in diabetes and muscular dystrophy and increased in cirrhosis. 4. The effects of infused leucine on blood glucose and ketone bodies differed according to the groups studied. 5. Since the traumatized patients were given sufficient energy and nitrogen and disposed of a leucine load at a different rate from the starved patients, the causes of the increase in blood concentration of leucine in these two conditions are different.
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PMID:The removal of infused leucine after injury, starvation and other conditions in man. 742 95

Hepatic encephalopathy in liver cirrhosis is due to several factors, including amino acid imbalance and hyperammonemia. Lactitol [correction of lactilol], a non adsorbable disaccharide, improves hepatic encephalopathy increasing bowel movements, modifying colonic bacteria and pH, and reducing blood ammonium. Ten patients with liver cirrhosis and longstanding stable hepatic encephalopathy were treated, after a period of drugs wash-out, with lactitol. A significant improvement of hepatic encephalopathy was observed, with a significant decrease of blood ammonium, related with the increase of stool frequency/day. Atrial natriuretic peptide decreased as well. Moreover, an increase of the ratio of plasma aliphatic amino acids (valine, leucine and isoleucine)/aromatic amino acid (tyrosine and phenylalanine) was observed. Lactitol is an effective drug in the treatment of chronic hepatic encephalopathy; its mechanism of action involves not only a decrease of blood ammonium but also modifications of the degree of plasma amino acid imbalance, and fluid and circulatory adjustments.
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PMID:Effects of lactitol [correction of lactilol] on hepatic encephalopathy and plasma amino-acid imbalance. 756 87

The amino acid composition of proteins from liver microsomes has been studied in rats and in human subjects with normal liver, with obstructive jaundice or liver cirrhosis. The pattern of the amino acid composition of microsomes appeared to be species-specific. Phenylalanine, threonine, serine, proline, histidine and [aspartic acid plus asparagine] were increased, while alanine, tyrosine, glycine and arginine were decreased in the human compared to the rat microsomes. In patients with obstructive jaundice of short duration (less than two months) only a slight decrease in leucine and phenylalanine could be noticed, while in the case of liver cirrhosis amino acid composition was markedly changed.
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PMID:Amino acid composition of rat and human liver microsomes in normal and pathological conditions. 757 35

Branched-chain amino acids (BCAA) are known to improve hepatic encephalopathy as well as protein malnutrition in cirrhosis. However, such effects in acute hepatic failure (AHF) remain to be elucidated. The current study was conducted to investigate whether BCAA improves protein metabolism in AHF. AHF was induced in male Donryu rats weighing approximately 230 g by giving 60 mg/kg lipopolysaccaride intravenously and 800 mg/kg D-galactosamine hydrochloride intraperitoneally. From 18 hours after injection, AHF rats and control rats were given one of the following five solutions intravenously for 6 hours: 1) saline, 2) 10% glucose, 3) standard 10% amino acid formula with total nitrogen content of 12.2 g/L and BCAA/aromatic amino acid molar ratio of 37.05, 4) BCAA-enriched solution with nitrogen content of 21.9 g/L and the ratio of 148.2, or 5) an active placebo against BCAA-enriched solution with nitrogen content of 21.9 g/L and the ratio of 37.05. In parallel, each group was given a continuous infusion of 14C-leucine. After the plasma radioactivity of 14C-leucine and the expired 14CO2 level reached a plateau, protein turnover was analyzed according to the kinetic model proposed previously by Waterlow. When compared with the control, rates of total protein turnover (total flux), oxidation, and breakdown all increased significantly in AHF. Infusion of standard 10% amino acid formula, BCAA-enriched solution or the placebo in AHF increased total flux and oxidation significantly as compared with the effect of saline or 10% glucose. Although saline, 10% glucose, standard 10% amino acid formula, and the placebo had no effect on synthesis rate, it was increased significantly with BCAA-enriched solution.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of branched-chain amino acid infusion on protein metabolism in rats with acute hepatic failure. 760 23

To analyze the pathological changes occurring in Fc receptors (FcRs) in sinusoidal endothelial cells (SECs) in chronic liver diseases, we first characterized immunohistochemically the SEC FcRs by using monoclonal antibodies (MAbs) to FcRs and then investigated the distribution of the SEC FcRs by using peroxidase-antiperoxidase IgG complexes as a ligand on frozen sections. MAb 2E1 to FcRII reacted with SECs in a similar manner to peroxidase-antiperoxidase IgG and blocked the peroxidase-antiperoxidase IgG binding to SECs, whereas MAbs 3G8 and Leu-11b to FcRIII did not. FcRs in normal liver were found along the sinusoidal walls, except for those in the outer periportal zones, but FcRs in chronic active hepatitis and cirrhosis were intermittently or focally absent. The lengths of the FcR-positive portion of sinusoids in unit areas were respectively about 54% and 76% of the normal values in active and inactive cirrhosis. Where FcRs were absent, the MAbs CD36, CD31, and EN4 revealed the presence of sinusoids and, in active cirrhosis, frequently the thickening of liver cell plates. The FcR-negative SECs in the outer periportal zones of normal livers were different from the SECs of other sites in the presence of PAL-E antigen and a rich amount of EN4 antigen, though these sinusoids possessed Kupffer cells and no perisinusoidal deposition of laminin. The FcR-negative SECs in liver diseases occasionally presented the character of ordinary blood vessels, viz., PAL-E antigen, CD34 antigen, and a deficiency of Kupffer cells, regardless of perisinusoidal laminin deposition. However, they preserved the character of normally FcR-possessing SECs, viz., CD36 antigen, and a small amount of EN4 and CD31 antigens. These findings indicate that the outer-periportal SECs in normal livers are phenotypically different from other SECs and that the SECs in diseased livers frequently undergo phenotypical changes, including loss of FcRs, regardless of perisinusoidal laminin deposition, i.e., capillarization of the sinusoids. These phenotypical changes in SECs may reduce the capacity of FcR-mediated IgG-IC metabolism in diseased livers.
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PMID:Defect of Fc receptors and phenotypical changes in sinusoidal endothelial cells in human liver cirrhosis. 768 39

To determine the hepatic fate of alpha-ketoisocaproate (KIC) in cirrhosis, six groups of isolated rat livers were perfused with 0, 0.5, 1 (with or without alpha-[1-14C]KIC), 2, and 5 mM KIC; control livers from healthy rats were studied in parallel under similar conditions. KIC was rapidly removed by the normal livers, whereas uptake was lower in the cirrhotic livers at all concentrations tested (at 2 mM, 4.04 +/- 0.33 vs. 6.32 +/- 0.58 mumol/min; P < or = 0.05). The transamination pathway, evaluated by leucine exchanges, was more important in the cirrhotic livers (25.4 vs. 6.8% in controls at 2 mM). The incorporation of alpha-[1-14C]KIC in proteins of cirrhotic liver was increased compared with controls (0.25 +/- 0.04% of alpha-[1-14C]KIC was incorporated in proteins excreted in perfusate vs. 0.20 +/- 0.04 in controls; P < or = 0.05). In addition, a line of evidence suggests that glutamine rather than glutamate is the N donor for leucine synthesis from KIC. The decarboxylation pathway evaluated by beta-hydroxybutyrate production and by 14CO2 release from alpha-[1-14C]KIC was reduced, respectively, by 40-85% (according to KIC dose) and by 24% at 90 min in cirrhotic livers compared with healthy livers. These results indicate a dramatic modification of KIC metabolism in the cirrhotic liver; its uptake by the liver is decreased and its incorporation into proteins is increased via an enhancement of transamination to leucine, probably as a consequence of an inhibition of branched-chain keto acid dehydrogenase.
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PMID:Metabolism of alpha-ketoisocaproic acid in isolated perfused liver of cirrhotic rats. 786 6

We studied the utilization of amino acids by the pancreas after its hormonal stimulation in diseases in which disturbances occur of amino acid and protein metabolism. After 45 minutes of intravenous infusion of secretin (1 CU/kg) and cerulein (75 ng/kg) we found a significantly lower (p 0.05) decrease of amino acid concentration than in healthy individuals, both in chronic pancreatitis and in undernutrition and post-inflammatory cirrhosis with decompensation of liver function. Greatest disturbances in amino acid utilization by the pancreas were found in the case of valine, leucine and isoleucine. The results of studies show certain limitations in the use of this method for the assessment of the exocrine function of the pancreas.
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PMID:[Evaluation of the influence of extrapancreatic factors (undernutrition, cirrhosis) on utilization of amino acids by the pancreas after its stimulation with secretin and cerulein]. 797 19

To investigate body protein turnover and the pathogenesis of increased concentration of plasma phenylalanine in liver cirrhosis, we have studied phenylalanine and leucine kinetics in cirrhotic (diabetic and nondiabetic) patients, and in normal subjects, both in the postabsorptive state and during a mixed meal, using combined intravenous and oral isotope infusions. Postabsorptive phenylalanine concentration and whole body rate of appearance (Ra) were approximately 40% greater (P < 0.05) in patients than in controls. Leucine concentrations were comparable, but intracellular leucine Ra was also increased (P < 0.05), suggesting increased whole body protein breakdown. Postprandial phenylalanine Ra was also greater (P < 0.05) in the patients. This difference was due to a diminished fractional splanchnic uptake of the dietary phenylalanine (approximately 40% lower in the cirrhotics vs. controls, P < or = 0.05). Postprandial leucine Ra was also increased in the patients, but splanchnic uptake of dietary leucine was normal. Thus both increased body protein breakdown and decreased splanchnic extraction of dietary phenylalanine can account for the increased phenylalanine concentrations in liver cirrhosis.
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PMID:Fasting and postprandial phenylalanine and leucine kinetics in liver cirrhosis. 804 3


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