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)

Data are submitted of clinical and biochemical examination of patients with cirrhosis of the liver complicated by different type encephalopathy. Examined before treatment and after the course of therapy involving administration of the acidifying drugs normase, dufalak were patients presenting with manifestations of hepatodepressive syndrome, parenchymal, mixed-type portosystemic encephalopathy, with n = 27, 12, 23 and 38 respectively. Clinical, biochemical findings, time course of the ratio blood serum levels of anticerebrotoxic: cerebrotoxic amino acids (valin + leucine + isoleucine) allowed judgement about efficacies of the treatments administered. The results obtained showed high clinical benefit from treatment with normase and dufalak in patients with hepatodepressive syndrome and portal-systemic encephalopathy.
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PMID:[Acidifying therapy in the combined treatment of patients with liver cirrhosis]. 967 Jun 65

The metabolic fate of leucine's first and second carbon may be different depending on the tissue in which leucine is metabolized, as well as the prevailing hormonal milieu of that tissue. However, previous studies of leucine kinetics in humans have used only leucine labeled (as tracer) at the first carbon position. Because cirrhosis is associated with factors (such as insulin resistance and altered fuel substrate utilization) that may influence how leucine is degraded, the kinetics of leucine's first and second carbon using a simultaneous infusion of [1-14C] leucine and [2-13C] leucine were studied in the postabsorptive state and during an amino acid infusion in 6 stable cirrhotic patients and 6 matched controls. The data were normalized for different body compartments that were quantified from the dilution of H2 [180] and bromide. The body cell mass, but not body weight or fat-free body mass, was decreased in cirrhosis (P < .001). In response to the amino acid infusion, total leucine appearance from proteolysis and leucine's incorporation into protein increased significantly in both groups, but were higher in cirrhotic patients. Endogenous protein breakdown decreased in normals but remained unchanged in cirrhosis. These alterations in leucine metabolism became more prominent when data were expressed based on the body cell mass rather than on body weight. The oxidation of leucine's first carbon (C1) was decreased in cirrhosis, but the oxidation of leucine's second carbon (C2) did not differ between groups during both the postabsorptive period and the amino acid infusion, while nonoxidative leucine degradation [the difference between the oxidation of leucine's (C1) and (C2)] was also decreased in cirrhosis. In addition, there was a positive correlation between nonoxidative leucine degradation (which represents leucine incorporation into fat), and the respiratory quotient obtained from indirect calorimetry (r = .87; P < .001). These data suggest that the extent of leucine carbon oxidation is dependent on whether fat or carbohydrate is the prevailing fuel substrate. In addition, cirrhotic patients have decreased nonoxidative leucine degradation and are unable to suppress endogenous protein breakdown normally in response to amino acid administration. These abnormalities may contribute to the diminished fat stores and body cell mass commonly observed in cirrhosis.
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PMID:Defective nonoxidative leucine degradation and endogenous leucine flux in cirrhosis during an amino acid infusion. 979 22

In the past year, some relevant papers on the mechanisms of malnutrition in cirrhosis have been published. Studies investigating the metabolic destiny of leucine after protein breakdown, which have contributed to a better understanding of the pathogenesis of muscle wasting and fat depletion in these patients, deserve particular mention. Also, the demonstration that chronically reducing hyperinsulinaemia in cirrhosis is able to improve insulin sensitivity opens novel pathogenic and therapeutic perspectives for such a metabolic derangement in these patients. Other papers dealt with unsaturated lipids, lipoperoxidation and antioxidants in chronic liver disease. However, randomized trials on parenteral or enteral nutrition in cirrhosis and liver transplantation are missing.
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PMID:Nutritional issues in cirrhosis and liver transplantation. 1058 78

The serpins are a family of proteinase inhibitors that play a central role in the control of proteolytic cascades. Their inhibitory mechanism depends on the intramolecular insertion of the reactive loop into beta-sheet A after cleavage by the target proteinase. Point mutations within the protein can allow aberrant conformational transitions characterized by beta-strand exchange between the reactive loop of one molecule and beta-sheet A of another. These loop-sheet polymers result in diseases as varied as cirrhosis, emphysema, angio-oedema, and thrombosis, and we recently have shown that they underlie an early-onset dementia. We report here the biochemical characteristics and crystal structure of a naturally occurring variant (Leu-55-Pro) of the plasma serpin alpha(1)-antichymotrypsin trapped as an inactive intermediate. The structure demonstrates a serpin configuration with partial insertion of the reactive loop into beta-sheet A. The lower part of the sheet is filled by the last turn of F-helix and the loop that links it to s3A. This conformation matches that of proposed intermediates on the pathway to complex and polymer formation in the serpins. In particular, this intermediate, along with the latent and polymerized conformations, explains the loss of activity of plasma alpha(1)-antichymotrypsin associated with chronic obstructive pulmonary disease in patients with the Leu-55-Pro mutation.
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PMID:Inactive conformation of the serpin alpha(1)-antichymotrypsin indicates two-stage insertion of the reactive loop: implications for inhibitory function and conformational disease. 1061 72

The cause of muscle wasting and decreased plasma levels of branched chain amino acids (BCAA), valine, leucine, and isoleucine in liver cirrhosis is obscure. Here we have evaluated the effect of hyperammonemia. Rats were infused with either an ammonium acetate/bicarbonate mixture, a sodium acetate/bicarbonate mixture, or saline for 320 minutes. The parameters of leucine and protein metabolism were evaluated in the whole body and in several tissues using a primed constant intravenous infusion of L-[1-14C]leucine. Ammonium infusion caused an increase in ammonia and glutamine levels in plasma, a decrease in BCAA and alanine in plasma and skeletal muscle, a significant decrease in whole-body proteolysis and protein synthesis, and an increase in leucine oxidized fraction. A significant decrease in protein synthesis after ammonium infusion was observed in skeletal muscle while a nonsignificant effect was observed in liver, gut, heart, spleen, and kidneys. We conclude that the decrease in plasma BCAA after ammonia infusion is associated with decreased proteolysis and increased leucine oxidized fraction.
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PMID:Effect of hyperammonemia on leucine and protein metabolism in rats. 1107 24

To evaluate the alteration of cerebral blood flow and oxygen metabolism in cirrhosis, we measured regional cerebral blood flow (rCBF), cerebral metabolic rate for oxygen (rCMRO2), and oxygen extraction fraction (rOEF) in twelve patients with cirrhosis (six with a history of hepatic encephalopathy and six without) and six age-matched controls using positron emission tomography. Regional CBF in whole brain was not different in cirrhotic patients from that in controls. In six cirrhotic patients with a history of hepatic encephalopathy, rCMRO2 was significantly lower in the frontal, temporal, parietal and occipital cortices, hippocampus, thalamus, cerebellum and brain stem, than that in each region of controls. On the other hand, rCMRO2 in six cirrhotic patients without a history of hepatic encephalopathy did not differ from the controls in all regions except for the frontal cortex. Regional OEF in cirrhotic patients without a history of hepatic encephalopathy was higher in the hippocampus and striatum than that in each region of controls. Among twelve cirrhotic patients, rCMRO2 in the occipital cortex and striatum correlated directly with plasma leucine levels, and rCMRO2 in the striatum directly correlated with plasma valine levels. Regional CMRO2 in the frontal cortex, temporal cortex, parietal cortex, white matter as well as brain stem correlated inversely with plasma phenylalanine levels, and rCMRO2 in the occipital cortex correlated inversely with plasma tyrosine levels. Brain oxygen metabolism is impaired in cirrhotic patients with a history of hepatic encephalopathy, but preserved in those without a history or in the early stage of cirrhosis. Reduced oxygen metabolism is related with altered amino acid metabolism.
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PMID:Alteration of regional cerebral metabolism in patients with cirrhosis in positron emission tomography. 1158 15

To investigate the anabolic effects of feeding in cirrhosis, we measured albumin fractional synthesis rate (FSR) and whole body protein synthesis in six nondiabetic patients with stable liver cirrhosis (three in the Child-Pugh classification Class A, three in Class B) and in seven normal control subjects, before and after administration of a 4-h mixed meal. Leucine tracer precursor-product relationships and whole body kinetics were employed at steady state. Basal levels of postabsorptive albumin concentration and FSR, whole body leucine rate of appearance, oxidation, and nonoxidative leucine disposal (NOLD, approximately equal to protein synthesis) were similar in the two groups. However, after the meal, in the patients neither albumin FSR (from 8.5 +/- 1.5 to 8.8 +/- 1.8 %/day) nor NOLD (from 1.69 +/- 0.22 to 1.55 +/- 0.26 micromol x kg(-1) x min(-1)) changed (P = nonsignificant vs. basal), whereas they increased in control subjects (albumin FSR: from 10.9 +/- 1.5 to 15.9 +/- 1.9 %/day, P < 0.002; NOLD: from 1.80 +/- 0.14 to 2.10 +/- 0.19 micromol x kg(-1) x min(-1), P = 0.032). Thus mixed meal ingestion did not stimulate either albumin FSR or whole body protein synthesis in compensated liver cirrhosis. The mechanism(s) maintaining normoalbuminemia at this disease stage need to be further investigated.
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PMID:Impairment of albumin and whole body postprandial protein synthesis in compensated liver cirrhosis. 1178 61

Lamivudine therapy for chronic hepatitis and decompensated liver cirrhosis related to the hepatitis B virus (HBV) resulted in improvement of liver function and inhibition of viral replication. Despite emergence of the HBV mutant, e-antigen seroconversion and improvement of liver function may be achieved with continuation of lamivudine therapy. Although hepatic decompensation has been reported in a few cases after the emergence of lamivudine-resistant mutants, fatal cases of non-transplant patients have only rarely been reported in the literature. Here, we describe a patient with HBV-related liver cirrhosis who died after a breakthrough infection with a lamivudine-resistant mutant. Hepatic failure and mortality developed after flare-up of severe hepatitis after 13 months of lamivudine treatment. Emergence of the HBV mutant with substitution of isoleucine for leucine at residue 426 (L4261) in combination with isoleucine for methionine at residue 550 (M5501) was observed at 10 and 13 months of treatment.
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PMID:Fatal hepatic failure after emergence of the hepatitis B virus mutant during lamivudine therapy in a patient with liver cirrhosis. 1191 2

Entire nucleotide sequences of the HBV genome typical for various stages of HBV carriers are currently unknown. Comparison between conserved sequences in HBeAg-positive asymptomatic carriers (HBeAg ASCs) and mutations characteristic for HBeAb-positive asymptomatic carriers (HBeAb ASCs) are of clinical importance. In this study, we determined the entire nucleotide sequences of the HBV genome of patients infected with genotype C (HBeAg ASCs, 11 cases; HBeAb ASCs, seven cases; patients with liver cirrhosis (LC), five cases). Mutations in the entire nucleotide sequences were found more frequently in HBeAb ASCs than in HBeAg ASCs. In the precore/core (preC/C) region, amino acid mutations were more frequent in HBeAb ASCs (3.03%) than in HBeAg ASCs (0.00%) and patients with LC (0.69%). It was suggested that the mutations in the preC/C region had a close relationship with clinical status of HBV carriers. Mutations of leucine to isoleucine at a.a. 100 of the core region and of threonine to serine at a.a. 340 of the polymerase region were found frequently in HBeAb ASCs. In patients with LC, it was suggested that defective interfering particles (DI particles) play a role in the progression of stages. We conclude that attention should be given to mutations at a.a. 340 of the polymerase protein in addition to core protein.
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PMID:Analysis of the entire nucleotide sequence of hepatitis B virus: characteristics of HBeAg-positive asymptomatic carriers, HBeAb positive asymptomatic carriers and patients with liver cirrhosis. 1219 73

The administration of branched-chain amino acids (BCAAs) to cirrhosis patients increases serum albumin levels and improves the blood Fischer's ratio. Although it has been reported that albumin synthesis in rat primary hepatocytes is diminished under lower Fisher's ratio conditions compared to normal Fischer's ratio conditions, the mode of action at the molecular level for these effects is still uncertain. It has been reported recently that the triggering signal for protein synthesis is transmitted through mTOR (mammalian target of rapamycin). We have had an interest in the mTOR signal transduction system. In the present study, we analyzed the mode of action of BCAA-induced albumin synthesis using rat primary hepatocytes. The BCAA mixture dose-dependently promoted the production of albumin, with leucine being the major effector half of which was inhibited by the mTOR inhibitor rapamycin. We also showed that only leucine induces P70 S6 kinase activation and 4E-BP1 phosphorylation which are mTOR's downstream translational effectors. These activations were completely inhibited by rapamycin. Our results suggest that BCAAs, especially leucine, promote the production of albumin in rat primary hepatocytes through an mTOR signal transduction system.
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PMID:Branched-chain amino acids promote albumin synthesis in rat primary hepatocytes through the mTOR signal transduction system. 1264 66


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