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)

Altered metabolism has been shown to exist in the settings of surgical stress, cancer, cirrhosis, sepsis, and trauma. Each condition is characterized by varying degrees of alteration in metabolic processes, and within a given patient, these metabolic alterations will change as the patient's status changes. Nutrition support is an integral part of the metabolic management of critically ill patients. Metabolic changes impact nutritional substrate requirements and utilization. As the patient's clinical condition deteriorates, clinical signs and symptoms become less reliable in predicting or assessing the existing physiologic state. Objective measurements are needed to define the metabolic status during these physiologic changes. The purpose of this article is to review selected indices that have been used to identify abnormalities in nutritional substrate metabolism. Although some of these tests are readily available and inexpensive, many have not been used outside of the research setting and, therefore, their clinical utility has yet to be determined. However, their use as research tools for defining metabolism warrants their inclusion in order to assist the clinician in interpreting research studies. The biochemical markers discussed include glucose, lactate, pyruvate, triglycerides, beta-hydroxybutyrate, acetoacetate, urinary nitrogen, acute phase proteins, visceral proteins, 3-methylhistidine, plasma amino acids, oxygen consumption, and resting energy expenditure. Each marker is defined in terms of its biochemical significance, and the literature describing changes that occur in various stress states is cited.
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PMID:Overview of biochemical markers used for nutrition support. 190 7

1. We investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indices of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with cirrhosis and in 11 healthy control subjects. Whole-body protein turnover was also measured using L-[1-13C]leucine. 2. Leg efflux of tyrosine was 45% greater in cirrhotic patients than in normal control subjects [-6.5(1.4 to -19.1) vs -4.2(-2.2 to -7.7) mumol min-1 100 mg-1 of leg, median (range), P less than 0.025]. 3-Methylhistidine efflux was not significantly altered. 3. In cirrhosis, whole-body leucine flux was normal but whole-body leucine oxidation was elevated so that whole-body protein synthesis was depressed by 17%. 4. The results indicate the predominant mechanism of muscle wasting in cirrhosis to be a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.
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PMID:Skeletal muscle and whole-body protein turnover in cirrhosis. 216 95

1. Muscle protein breakdown in vivo has been studied by measurements of urinary 3-methyl-histidine/creatinine ratios. No differences were found between control subjects and chronic alcoholics either with or without proximal muscle wasting or cirrhosis. 2. Calculation of muscle turnover rates, with the correction of Afting et al. (1981, Biochemical Journal, 200, 449-452) for non-skeletal muscle contributions of 3-methylhistidine and creatinine, showed lower values for alcoholics compared with controls. 3. Tissue activities of a neutral protease, assayed by a novel, rapid and sensitive fluorimetric method, were similar in patients and controls. The activity did not vary with severity of atrophy or the presence of cirrhosis. 4. No evidence was therefore obtained to suggest that alcoholic myopathy is due to increased muscle breakdown.
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PMID:Assessment in vitro and in vivo of muscle degradation in chronic skeletal muscle myopathy of alcoholism. 248 72

To investigate the relationship between hypogonadism and altered amino acid metabolism in patients with liver cirrhosis, we measured the basal levels of plasma testosterone, estradiol, and free amino acids, plus urinary 3-methylhistidine excretion, in 16 control and 19 cirrhotic patients. The concentration of plasma testosterone correlated significantly with that of plasma branched-chain amino acids, and inversely with urinary 3-methylhistidine excretion. This suggests that hypogonadism causes a disturbance in amino acid metabolism at least partly related to an augmented muscle protein turnover.
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PMID:Hypogonadism in liver cirrhosis: implication in altered amino acid metabolism in muscle. 337 5

Administration of total parenteral nutrition (TPN) solutions high in branched chain amino acids (BCAA) is thought to improve metabolic support during stress. This prospective, randomized, double blind study compared 45 per cent BCAA with 25 per cent BCAA in 12 patients. Seven patients had multiple trauma; two, gastrointestinal surgery; one, pancreatitis; and two, cirrhosis. The TPN regimen was 1.0-1.5 gm/kg/day amino acids and 30-45 glucose kcal/kg/day. The BCAA formula used was high in isoleucine and valine, but not leucine. Amino acid plasma levels, blood chemistries, 3-methylhistidine excretion, and nitrogen balance were studied. Control studies showed negative nitrogen balance (-7.1 +/- 2.9 gm) (mean +/- SEM), elevated insulin (61 +/- 21 microunit/ml), and elevated 3-methylhistidine (3MH) excretion (688 +/- 309 micromol); plasma leucine (93 +/- 11 nmol/ml) and isoleucine (37 +/- 23) were low, and valine (155 +/- 20) was elevated. Plasma methionine (40 +/- 9) and tyrosine (70 +/- 12) were high normal. Phenylalanine (85 +/- 5) was elevated. Both groups showed increased nitrogen excretion and positive nitrogen balance during the study (25 per cent, 2.0 +/- 1.4 gm/day; 45 per cent, 1.2 +/- 2.6 gm/day). Three-methylhistidine excretion changed little in either group (557 +/- 149, 414 +/- 91), insulin rose (135 +/- 27, 65 +/- 19), and plasma leucine (82 +/- 4, 71 +/- 9) changed little. Plasma isoleucine (51 +/- 3, 155 +/- 16) and valine (173 +/- 11, 691 +/- 23) both rose, more in the 45 per cent group. Methionine (67 +/- 12, 37 +/- 4) and tyrosine (51 +/- 6, 50 +/- 10) changed little.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of total parenteral nutrition with 25 per cent and 45 per cent branched chain amino acids in stressed patients. 393 93

Patients with hepatic cirrhosis often are malnourished and wasted. If portal-systemic encephalopathy (PSE) develops, restriction of dietary protein in an attempt to treat encephalopathy may further promote negative nitrogen balance. There is considerable interest in providing nutritional supplements to patients with cirrhosis and PSE which would lead to improvement in nitrogen balance while improving or at least not worsening PSE. Amino acid supplements designed to correct the abnormal amino acid pattern characteristically found in patients with cirrhosis and PSE are under investigation as potential therapeutic agents. The levels of the branched chain amino acids (BCAAs) are decreased in almost all patients with cirrhosis and PSE. The exact mechanism for the reductions in BCAA concentrations is unknown. Furthermore, aromatic amino acids (AAA) and methionine (MET) concentrations are usually increased in these patients. It has been suggested that BCAAs and neutral amino acids compete for transport across the blood-brain barrier and that a decrease in BCAA concentrations promotes entrance of neutral amino acids into the brain. Aromatic amino acids, MET, and their derivatives may have a role in the production of PSE. These observations have increased interest in the potential therapeutic benefit of administering BCAAs to patients with cirrhosis and PSE in order to decrease the entrance of putative toxins into the brain. Treatment trials using BCAAs alone or in solutions containing other amino acids in patients with cirrhosis and PSE have given conflicting results. In one trial, there appeared to be less PSE induced by a BCAA-enriched solution when compared to equinitrogenous dietary protein. However, other controlled studies have not demonstrated any advantage to the addition of BCAAs as compared to placebo with regards to reducing mortality or improving cerebral function in patients with acute cirrhosis and PSE. Some of the differences in study outcomes may relate to the patient population evaluated; the type, amount, and duration of treatment; and whether other therapy was administered. BCAA supplements may also be useful in minimizing or reversing the catabolic state characteristic of patients with cirrhosis. A reduction of increased urinary 3-methylhistidine excretion by infusions of BCAAs in cirrhotic patients suggests an anticatabolic effect. These potential anticatabolic effects of BCAAs are most interesting and deserve further study.
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PMID:Branched chain amino acid therapy in liver disease. 393 6

Management of protein-calorie malnutrition found in 32 patients with severe liver diseases such as fulminant hepatitis and cirrhosis of the liver was carried out using 2 types of synthetic amino acid solution (Hep-OU and Fischer solution) for intravenous and enteral alimentations with rapid monitoring of serum aminogram. Intravenous hyperalimentation of these cases resulted in maintenance of nutritional status with improvement of nitrogen balance and normalization of impaired serum aminogram. During this study, however, nutritional support was initiated only when intractable ascites, upper gastrointestinal bleeding and hepatic encephalopathy were observed. In 2 cases of fulminant hepatitis with sepsis and 3 hepatoma patients with ascites, elemental diet containing maltose and amino acids was used to supply sufficient amounts of nutrients in a minimum volume of water. These techniques with simultaneous monitoring of urinary excretion of 3-methylhistidine and creatinine height index as nutritional parameters make nutritional management easy for patients with liver disease.
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PMID:Nutritional management of patients with severe liver disease by using intravenous hyperalimentation and elemental diet. 676 41

1. The urinary excretion of 3-methylhistidine and creatinine was measured in 15 controls and in two groups of 15 patients with liver cirrhosis, with and without severe muscle wasting. All subjects were on a meat-free diet. The values obtained were used to calculate the fractional catabolic rate of myofibrillar protein. 2. In patients without muscle wasting 3-methylhistidine excretion was high in the presence of normal urinary creatinine. The fractional breakdown rate was significantly increased as compared with that of controls. 3. In patients with severe muscle wasting 3-methylhistidine excretion was normal and urinary creatinine was remarkably reduced. The myofibrillar catabolic rate was further increased compared with that of controls and of the other group of patients. 4. 3-Methylhistidine and creatinine excretion allow a complete evaluation of myofibrillar protein degradation, which appears to be remarkably increased in cirrhotic patients. The relevance of increased myofibrillar protein turnover in muscle wasting of subjects with advanced cirrhosis remains to be determined.
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PMID:Myofibrillar protein catabolic rates in cirrhotic patients with and without muscle wasting. 708 59

Previous studies have shown that nocturnal glucose supplementation and a late evening meal reduced raised protein turnover rates and led to a better nitrogen balance in patients with cirrhosis. In this study, we investigated whether or not oral branched chain amino acid (BCAA) supplementation in the late evening would improve the nutritional state of patients with liver cirrhosis. Fourteen patients with liver cirrhosis spent two 14 day periods in the ward. All the patients received three meals a day and two doses of BCAA supplementation. Meals were given at 0800, 1200, and 1830. BCAA supplementation was given at 0830 and 1900 (after dinner) and at 0830 and 2230 (late evening), respectively. The daily excretion of 3-methylhistidine, the ratio of 3-methyhistidine to creatinine, and serum free fatty acid in the late evening treatment group were significantly lower as compared to the usual treatment group. These results suggest that oral BCAA supplementation in the late evening also may be useful in improving protein catabolism and lypolysis in cirrhotic patients.
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PMID:Effect of oral branched chain amino acid supplementation in the late evening on the nutritional state of patients with liver cirrhosis. 1167 4