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)

Ten patients were given 3MU/3 times/week of r-interferon alpha 2b for 4 months; six patients were given 1MU/3 times/week for 4 months. The choice of these regimes has been based on the number of platelets. Among the patients treated with 9MU/week we observed a type I response (alanine-aminotransferases normalization) in 40% of cases, a type II (ALT fifty percent reduction) in 40% of cases, and a type III (no response) in 20% of cases. Among the patients treated with 3MU/week we observed a type II response in 16.7% and a type III in 83.3% of cases. Treatment of Child A liver cirrhosis with r-interferon demonstrates to rise, therefore, the same percentage of response which are obtained in the treatment of chronic active hepatitis, when the same doses are administered (9MU/week).
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PMID:[Interferon therapy in liver cirrhosis]. 846 87

Glutathione and amino acid concentrations were measured in arterial and hepatic vein plasma in four healthy volunteers and two patients with cirrhosis. There was no significant splanchnic efflux of glutathione (95% confidence limits, -0.501 to 0.405 mumol/min). After infusion of N-acetylcysteine (NAC) in a high dose (150 mg/kg body weight primer plus 15 mg/(h x kg BW), corresponding to treatment of acetaminophen overdose, there was no change in the splanchnic glutathione efflux (95% confidence limits, -0.531 to 0.375 mumol/min). NAC increased hepatic plasma flow rate from 0.90 +/- 0.531 min-1 to 0.97 +/- 0.11 (mean +/- SEM; p < 0.05). The effects of NAC treatment on plasma amino acids corresponded to an increased load on hepatic metabolic N conversion and transamination among nonessential amino acids. Splanchnic uptake of serine, alanine, cystine, isoleucine, and phenylalanine increased after NAC compatible with stimulated hepatic glutathione synthesis. In contrast to the rat, plasma glutathione in man probably originates mainly from extrahepatic tissues.
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PMID:No net splanchnic release of glutathione in man during N-acetylcysteine infusion. 851 1

Two siblings presented with neonatal cholestasis and early liver insufficiency. The older was admitted for end-stage cirrhosis with severe hypoglycemia and had long-term successful liver transplant at the age of 15 months. The second child presented a similar neonatal history of cholestasis, hypoglycemia, hyperlactacidemia, liver insufficiency and progressive cirrhosis. Extensive work-up excluded all known causes of neonatal cholestasis. Gluconeogenesis was found normal following alanine and fructose infusion. Repeated hypoglycemia with early post-prandial hyperlactacidemia led us to investigate the mitochondrial respiratory chain enzyme activities. Selective defects of complexes I, III and IV, coded by mitochondrial DNA, were detected in liver tissue of this patient and on preserved frozen tissue from his sibling, whilst normal activities were found in liver tissue samples from control patients with end-stage liver diseases. No extrahepatic manifestations were found. We conclude that liver deficiency of mitochondrial respiratory chain enzymes may cause liver disease in neonates, associated with hypoglycemia and post-prandial hyperlactacidemia. The disease is cured by liver transplantation.
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PMID:Mitochondrial respiratory chain defect: a new etiology for neonatal cholestasis and early liver insufficiency. 855 Sep 93

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

Zinc deficiency is common in cirrhosis and has been involved in the altered nitrogen metabolism. In this study, we measured the effects of zinc supplementation on the dynamics of amino acid-derived urea synthesis in cirrhosis with mild or latent encephalopathy. The hepatic conversion of amino acids into urea was studied in eight patients with advanced cirrhosis under controlled conditions of substrate availability (continuous alanine infusion), before and after 3-month oral zinc sulfate supplementation (600 mg/d). Eight more patients, matched for hepatocellular failure and encephalopathy, served as controls. Plasma zinc levels were reduced in all patients and returned to normal after oral zinc. The alanine-stimulated urea nitrogen synthesis rate in relation to alpha-amino-N concentration--the functional hepatic nitrogen clearance--increased by 25% after zinc supplementation, i.e., more urea was produced at any alpha-amino-N concentration. Basal and alanine-induced glucagon decreased by 50%, and the ammonia response to alanine decreased by 30%. Psychometric tests improved, as did routine and dynamic liver function tests and the Child-Pugh score. Also, the plasma concentration of lipid peroxides was reduced by zinc. No significant changes were observed in the control group. Our data indicate that long-term oral zinc speeds up the kinetics of urea formation from amino acids and ammonia. Changes in the hormonal drive and/or the antioxidant activity of zinc might be involved in the general improvement in liver function, whereas the beneficial effects on encephalopathy might stem from decreased ammonia.
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PMID:Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis. 862 Nov 38

The cirrhotic liver has been shown to be resistant to the actions of various glucoregulatory hormones. The objective of this study was to investigate the effects of epinephrine on hepatic glucose metabolism in cirrhotic patients. Thirteen cirrhotic and eight healthy subjects were studied. Hepatic glucose production and turnover of alanine and glycerol were measured using stable isotope technique before and during 70 and 150 minutes of epinephrine infusion (0.1 microgram/kg/min). beta-Adrenoreceptor binding sites and affinity in mononuclear leukocyte membranes also were determined. Hepatic glucose production and alanine turnover in normals significantly increased during epinephrine infusion, but did not change in cirrhotics. Glycerol turnover increased after 70 minutes of epinephrine infusion in both groups. Epinephrine induced a significant rise of high-affinity beta-adrenoreceptor binding sites in normals, yielding a significant correlation between hepatic glucose production and receptor density (r = .94, P < .0001). In cirrhotic patients, similar changes in the number of high-affinity beta-adrenoreceptors were observed, but no correlation with hepatic glucose production was detected. The cirrhotic liver did not respond normally to the stimulatory effect of epinephrine on hepatic glucose production. Because this blunted response was not related to changes of beta-adrenoreceptors, our findings suggest that epinephrine resistance in cirrhosis was caused by a postreceptor defect.
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PMID:Effects of epinephrine on glucose metabolism in patients with alcoholic cirrhosis. 869 Apr 1

Diet protein increases whereas carbohydrates decrease urea synthesis. Traditionally, these effects have been explained by changes in substrate supply. Diet protein intake increases whereas carbohydrate decreases blood amino acid concentration. However, glucose also decreases urea synthesis by a hepatic mechanism independent of the decrease in blood amino acid concentration. Whether this is due to an effect of glucose in itself, or whether the fall in glucagon or the rise in insulin is responsible, was not known. This survey deals with the effect of an increase in diet protein intake and of the separate effects of glucose, glucagon and insulin on functional hepatic nitrogen clearance in normal man and in patients with cirrhosis of the liver. The functional hepatic nitrogen clearance is calculated as the slope of the linear regression analysis of alanine-stimulated urea synthesis rate and blood alpha-amino nitrogen concentration, and expresses urea synthesis independent of changes in blood amino acid concentration. In patients with cirrhosis, hepatic nitrogen clearance is reduced in parallel with liver cell mass, despite high glucagon concentration that would normally up-regulate the process. In both healthy subjects and in patients with cirrhosis, an increase in diet protein intake (plus approximately 50 g/day) for 14 days increases hepatic nitrogen clearance by 40%. Thus, in addition to the substrate effect, protein intake increases urea synthesis by an effect in the liver, probably by enzyme formation. What induces this is not clear but high postprandial levels of glucagon may be involved. Although the effect is qualitatively intact in the patients, the response relative to the increase in protein intake is reduced by two-thirds. The effect may be important to control blood amino acid concentration during a high protein diet and may partly explain why patients with cirrhosis usually tolerates protein hyperalimentation without developing hepatic encephalopathy. It is shown that the reduction of hepatic nitrogen clearance by glucose depends on hyperglycaemia, and is accomplished by the additive effects of a direct hormone-independent action of glucose, and indirectly via suppression of glucagon. Insulin is not a direct controller of hepatic nitrogen clearance, but is still considered an important regulator of urea synthesis by its reducing effects on blood amino acid concentration. High experimental glucagon levels overrule the normal suppressive effect of glucose. In contrast, it is shown that the sugar-alcohol xylitol normalises the glucagon induced increase in hepatic nitrogen clearance. During normal glucagon levels xylitol exerts only a very little decrease in hepatic nitrogen clearance. In patients with cirrhosis, glucose does not down-regulate hepatic nitrogen clearance. However, when the spontaneous high glucagon levels are normalised by somatostatin, glucose decreases hepatic nitrogen clearance. This shows that the direct hormone-independent effect of glucose is intact. These findings indicate that the high glucagon levels during spontaneous hormone responses overrule the suppressive effect of glucose. Incomplete glucose suppression of glucagon secretion during alanine infusion contributes to the high glucagon levels. The removal of the high glucagon levels decreases hepatic nitrogen clearance in itself. Thus, the hyperglucagonaemia may be a compensatory mechanism by which the cirrhotic liver to some extent reestablishes its capacity to produce urea. The consequence is the defective down-regulation of hepatic nitrogen clearance by glucose. The reduction in urea synthesis by glucose, i.e. its nitrogen sparing effect, is accomplished by two different mechanisms: A hepatic component (reduction of the hepatic nitrogen clearance) and a peripheral component (reduced substrate availability mediated by the insulin response). This is an extension of former thoughts according to which glucose reduces urea synthesis due solely to
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PMID:Regulation of urea synthesis by diet protein and carbohydrate in normal man and in patients with cirrhosis. Relationship to glucagon and insulin. 923 44

Glucose intolerance and diabetes mellitus are both prevalent in patients with chronic liver diseases. We examined the efficacy and systemic safety of therapy with an alpha-glucosidase inhibitor, acarbose, in diabetes mellitus associated with chronic liver diseases. Twenty patients with chronic hepatitis or liver cirrhosis and overt diabetes mellitus received acarbose (taken orally) for 8 weeks. The initial dosage of acarbose was 50 mg three times daily, taken before meals; this was increased to 100 mg three times daily after 2 weeks. The mean fasting plasma glucose level was 173.7 +/- 18.6 mg/dl (mean +/- SE) at entry, and was significantly decreased to 132.9 +/- 7.5 mg/dl (P < 0.05) after 8 weeks of acarbose treatment. The improved glycemic control was reflected by a significant decrease in glycosylated hemoglobin (HbA1c) from 7.2 +/- 0.3% at entry to 6.3 +/- 0.2% (P < 0.05) after 8 weeks. Serum levels of both aspartate and alanine aminotransferases fluctuated during acarbose treatment, probably due to the natural course of chronic liver diseases, but the mean values had decreased after 8 weeks of treatment. Plasma ammonia levels increased, from 61.3 +/- 10.7 micrograms/dl to 71.1 +/- 9.6 micrograms/dl after 8 weeks of acarbose treatment but the increase was not significant. Clinically significant elevation of plasma ammonia concentration was seen in 2 cirrhotic patients (121 and 124 micrograms/dl); this was asymptomatic and gradually returned to the normal range despite continuous acarbose treatment in one patient, and was reversed after the withdrawal of acarbose with the concomitant administration of lactulose in the other patient. No other blood tests results, including albumin, cholinesterase, and prothrombin time, or lipid profile and nutritional status, in terms of rapid turnover proteins, prealbumin, retinol binding protein, and transferin, were altered throughout the study period. These results indicate that diabetes mellitus associated with chronic liver diseases may be safely and effectively treated with acarbose. However, clinicians must be aware of the possibility of hyperammonemia when they prescribe acarbose for patients with diabetes mellitus and advanced liver cirrhosis.
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PMID:Safe and effective treatment of diabetes mellitus associated with chronic liver diseases with an alpha-glucosidase inhibitor, acarbose. 943 16

The results of liver function tests and ultrasonographical findings were analysed in 7 dogs that were intravenously injected dimethylnitrosamine (DMNA 2 mg/kg body weight) on 2 consecutive days each week for 10 weeks. Typical clinical signs and similar changes in liver enzyme concentrations that develop in dogs with natural cirrhosis were observed in this canine model. Severe anaemia and a significant reduction in the platelet numbers occurred in the dogs that died in the 5th week, while in all the other dogs these parameters decreased slightly. Serum total protein and the albumin/globulin ratio decreased gradually while the alkaline phosphatase, alanine amino transferase, aspartate amino transferase and gamma glutamyl transpeptidase activities increased significantly (p < 0.05) in all dogs after beginning the administration of DMNA. Ultrasound findings of a coarsened and heterogeneous echo pattern with increased echogenicity that are characteristic of canine cirrhosis were noticed at the same time when the changes in liver enzymes became evident. Present results suggest that ultrasonography in conjunction with liver function tests may be useful in the evaluation of experimentally induced liver cirrhosis.
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PMID:Ultrasonography, biochemical and hematological profiles in liver disease caused by intravenous administration of dimethylnitrosamine in dogs. 943 16

Prostaglandins of the E (PGE) series have long been considered "catabolic" hormones, but recent data suggest that they may be secreted in critically ill patients to counteract stress hormones, stimulating protein synthesis. Their use is under scrutiny to improve hepatic microcirculation and as cytoprotective agents. We tested the effects of PGE1 on hepatic and whole-body nitrogen metabolism in eight patients with cirrhosis. Urea-nitrogen synthesis rate, alpha-amino-nitrogen levels, and nitrogen exchange were measured in the basal, postabsorptive state and in response to continuous alanine infusion, in paired experiments, during superinfusion of PGE1 or saline. Splanchnic and systemic hemodynamics were assessed by echo-Doppler at the beginning and at the end of each experiment. PGE1 produced a rapid fall in plasma amino acids and in urea-nitrogen synthesis rate, as well as a positive nitrogen exchange. The slope of the regression of alpha-amino-nitrogen levels on urea-nitrogen synthesis rate, a measure of liver cell metabolic activity, was not affected, but the regression line was shifted rightward, suggesting a nitrogen-sparing effect of PGE1. Mesenteric artery and portal flow were unchanged, whereas femoral artery flow increased by 30%. Insulin and glucagon levels were not systematically different. We conclude that PGE1 reduces hepatic urea synthesis rate, independent of hormones and/or hepatic flow, possibly acting at the peripheral level on amino acid transport, thus reducing amino acid supply to the liver. The resulting net nitrogen sparing might be the basis for the beneficial effect of PGE1 in clinical hepatology.
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PMID:Effects of systemic prostaglandin E1 on hepatic amino acid-nitrogen metabolism in patients with cirrhosis. 950 Jul 12


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