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

A controlled study was carried out in two groups of 20 patients with cirrhosis of the liver and deep coma in order to compare the efficacy of intravenous branched-chain amino acid solutions in 20% glucose (group A) vs lactulose plus glucose in isocaloric amount (group B). There were 3 drop-outs from each group. Plasma amino acids and ammonia were assayed at fixed intervals throughout the 10-day observation period. Routine tests were assayed daily. Complete mental recovery was obtained in 70% of patients in group A and in 47% in group B. The difference was not significant, likely due to the lack of placebo group. With the exception of free tryptophan/all competing amino acids ratio, the modifications in plasma amino acid levels showed no correlation with the clinical course under either treatment. Ammonia, like free tryptophan, decreased significantly upon mental recovery, paralleling the clinical course throughout the study. In conclusion, branched-chain amino acids are at least as effective as lactulose in deep hepatic coma. It is suggested that branched-chain amino acids may reverse coma either by competing with brain entry of the aromatic amino acid or by metabolically decreasing free tryptophan and ammonia.
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PMID:Branched-chain amino acids vs lactulose in the treatment of hepatic coma: a controlled study. 674 58

Because of its specific hepatic degradation tryptophan was orally administered (50 mg/kg) to patients with various chronic liver diseases (n = 30) and to healthy volunteers (n = 8) as a test for hepatic function. The plasma half life of tryptophan was determined between 4 and 8 h after the amino acid load. It was found that in patients with cirrhosis (n = 25) the half life of tryptophan was prolonged to 4.7 +/- 0.4 h (means +/- SD), compared to 2.0 +/- 0.1 h in the controls. The tryptophan half life also correlated with the plasma concentration of albumin, bilirubin, cholinesterase and prothrombin time in these patients. In addition a significant correlation was observed with the galactose elimination capacity and the 45 min retention of BSP. Thus, the oral tryptophan loading test may be suitable for a more specific determination of functional impairment of the liver in chronic liver disease. In decompensated cirrhotic patients alterations of the tryptophan metabolism seen to be related to indicators of hepatic encephalopathy. The test may therefore be used to assess the degree and risk of hepatic encephalopathy in such patients.
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PMID:[Tryptophan loading test as a function parameter in liver diseases]. 686 62

Plasma prolactin levels are often raised in patients with liver cirrhosis and portal hypertension. To obtain more insight into the underlying mechanisms we examined the synthesis and release of prolactin in male rats with partially ligated portal veins. Portal hypertension led to an increase in pituitary prolactin, plasma prolactin, and plasma 17 beta-estradiol, and a decrease in hypophyseal stalk dopamine levels. Castration decreased plasma prolactin levels and prevented the induction of hyperprolactinemia by portal hypertension. Administration of dihydrotestosterone to castrated animals did not affect prolactin levels in the pituitary gland or in the plasma. Plasma tryptophan and tyrosine concentrations did not change in portal hypertension. A low protein diet caused a decrease in plasma tryptophan and an increase in plasma tyrosine levels without affecting prolactin levels in either controls or portal hypertensive rats. The hyperprolactinemia of portal hypertension is probably caused by elevated estrogen levels which interfere with hypothalamic dopamine release. Changes in plasma amino acid levels are of little importance in the regulation of prolactin release in portal hypertensive rats.U
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PMID:hyperprolactinemia of portal hypertension in rats. 705 21

The competition of free fatty acids and bilirubin in the binding of tryptophan to albumin was studied in 12 controls and 36 cirrhotics at various stages of hepatic encephalopathy. Total tryptophan was not significantly altered in cirrhotics, while free tryptophan progressively increased with the deterioration of their mental state. Bound tryptophan levels were consequently reduced in patients with cirrhosis, mainly in the presence of hepatic encephalopathy, and strictly correlated with albumin (r = 0.80). The ratio bound tryptophan/albumin, which represents the muMoles of tryptophan bound by 1 gram of albumin, did not show significant difference in the various groups of patients. No correlation was found between this ratio and the levels of free fatty acids and bilirubin, which were raised in cirrhotics. Our data suggest that the fall in albumin levels, but not the increase in free fatty acids or bilirubin, may play a role in increasing free tryptophan levels in cirrhotics. Thus, marked hypoalbuminemia may be a risk factor of hepatic encephalopathy in patients with cirrhosis.
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PMID:Binding of tryptophan to albumin in liver cirrhosis: a reappraisal of the problem. 721 52

The concentration of adenosine 3':5'-cyclic monophosphate in the spinal fluid of ten patients with liver dysfunction was analyzed. Ages of the patients ranged from 31 to 75 years. The state of consciousness varied between normality and stupor. After a liver biopsy the diagnoses were as follows: cirrhosis in six cases, porphyria cutanea tarda in one case, hepatic metastases in two cases and Wilson's disease in one case. Mean values in these patients (22.91 +/- 4.18 pM/ml) have been significantly greater (p less than 0.0005) than those in ten control individuals (15.55n control individuals (15.44 +/- 3.66 pM/ml). Values corresponding to two patients in coma were still higher (52.62 and 36.50 pM/ml respectively). A previous lumbar puncture carried out in one of these patients when he was conscious showed a figure of 23 pM/ml. These results suggest a progressive rise of cyclic adenosine monophosphate in the spinal fluid in relation to clinical impairment, and may indicate a similar behaviour for this nucleotide to that of tryptophan, as reported by other authors. These findings point toward the role of the alteration of neurotransmitters in the pathogenesis of hepatic coma.
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PMID:[Cyclic adenosine monophosphate in the cerebrospinal fluid of patients with liver disease (author's transl)]. 737 36

To date, no attempt has been made to study alterations occurring in the amino acid profile in chronic models of thioacetamide-induced liver cirrhosis. In this work, changes in serum amino acids and proteins in rats with thioacetamide-induced liver cirrhosis are reported, together with changes in enzyme activities in the liver and serum. Seventeen female Wistar rats were used. Eight rats were given 300 mg thioacetamide/l in drinking water for 4 months and nine rats were given water ad libitum during the same time-period. Significant increases in glycine, alanine, serine, methionine, glutamate, ornithine, phenylalanine, tyrosine, histidine and proline were observed in rats with the resulting experimental liver cirrhosis. Threonine, taurine, glutamine, lysine and citrulline tended to increase while isoleucine, leucine, aspartate, arginine and tryptophan tended to decrease. Total and nonessential amino acids increased significantly in cirrhotic animals. Total essential and aromatic amino acids tended to increase in the thioacetamide-treated group, whereas branched chain amino acids tended to decrease in the same group. Regarding serum proteins, a decrease in albumin concentration in the thioacetamide-treated animals was the only change detected. The liver enzyme activities under observation (aspartate and alanine aminotransferases, glutamate dehydrogenase and threonine deaminase) were lower in the thioacetamide group. Decreases were significant for both transaminases and threonine deaminase. Results for serum activities showed that transaminases did not change in thioacetamide-treated rats in comparison with controls. In contrast, alkaline phosphatase rose dramatically in cirrhotic rats. We conclude that the serum amino acid pattern in this chronic model of liver cirrhosis resembles in part that of the corresponding human disease.
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PMID:Serum amino acid changes in rats with thioacetamide-induced liver cirrhosis. 857 92

A child with Alagille syndrome, characterized by intrahepatic bile duct paucity, developed severe liver cirrhosis and was referred for liver transplantation. In the pre-transplantation evaluation, scintigraphic scans were performed using 99mTc-galactosyl serum albumin (99mTc-GSA) as a hepatoreceptor binding agent and 99mTc-pyridoxyl-5-methyl-tryptophan (99mTc-PMT) as a hepatobiliary agent. These studies demonstrated severe hepatobiliary dysfunction with an area of increased focal uptake in the liver. Histological examination at surgery confirmed that this focal lesion was an area of compensatory hyperplasia in advanced biliary cirrhosis. We present the usefulness of these tracers for detecting the focal hyperplasia of the liver.
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PMID:Focal liver hyperplasia in Alagille syndrome: assessment with hepatoreceptor and hepatobiliary imaging. 870 75

Transthyretin and retinol-binding protein are sensitive markers of acute protein-calorie malnutrition both for early diagnosis and dietary evaluation. A preliminary study showed that retinol-binding protein is the most sensitive marker of protein-calorie malnutrition in cirrhotic patients, even those with the mild form of the disease (Child A). However, in addition to being affected by protein-calorie malnutrition, the levels of these short half-life-liver-produced proteins are also influenced by other factors of a nutritional (zinc, tryptophan, vitamin A, etc) and non-nutritional (sex, aging, hormones, renal and liver functions and inflammatory activity) nature. These interactions were investigated in 11 adult male patients (49.9 +/- 9.2 years of age) with alcoholic cirrhosis (Child-Pugh grade A) and with normal renal function. Both transthyretin and retinol binding protein were reduced below normal levels in 55% of the patients, in close agreement with their plasma levels of retinol. In 67% of the patients (4/6), the reduced levels of transthyretin and retinol-binding protein were caused by altered liver function and in 50% (3/6) they were caused by protein-calorie malnutrition. Thus, the present data, taken as a whole, indicate that reduced transthyretin and retinol-binding protein levels in mild cirrhosis of the liver are mainly due to liver failure and/or vitamin A status rather than representing an isolated protein-calorie malnutrition indicator.
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PMID:Plasma levels of transthyretin and retinol-binding protein in Child-A cirrhotic patients in relation to protein-calorie status and plasma amino acids, zinc, vitamin A and plasma thyroid hormones. 961 Dec 91

The mutation in the Z deficiency variant of alpha1-antitrypsin perturbs the structure of the protein to allow a unique intermolecular linkage. These loop-sheet polymers are retained within the endoplasmic reticulum of hepatocytes to form inclusions that are associated with neonatal hepatitis, juvenile cirrhosis, and hepatocellular carcinoma. The process of polymer formation has been investigated here by intrinsic tryptophan fluorescence, fluorescence polarization, circular dichroic spectra and extrinsic fluorescence with 8-anilino-1-naphthalenesulfonic acid and tetramethylrhodamine-5-iodoacetamide. These biophysical techniques have demonstrated that alpha1-antitrypsin polymerization is a two-stage process and have allowed the calculation of rates for both of these steps. The initial fast phase is unimolecular and likely to represent temperature-induced protein unfolding, while the slow phase is bimolecular and associated with loop-sheet interaction and polymer formation. The naturally occurring Z, S, and I variants and recombinant site-directed reactive loop and shutter domain mutants of alpha1-antitrypsin were used to demonstrate the close association between protein stability and rate of alpha1-antitrypsin polymerization. Taken together, these data allow us to propose a kinetic mechanism for alpha1-antitrypsin polymer formation that involves the generation of an unstable intermediate, which can form polymers or generate latent protein.
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PMID:A kinetic mechanism for the polymerization of alpha1-antitrypsin. 1009 40


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