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)

Hyaluronan (hyaluronic acid) is a linear polysaccharide formed from disaccharide units containing N-acetylglucosamine and glucuronic acid. It is ubiquitously distributed in the organism but is found in the highest concentrations in soft connective tissues. The molecular weight of hyaluronan is usually in the order of 10(6) to 10(7). Due to hydrogen bonding, the chain is rather stiff and the molecule behaves in solution as an extended, randomly kinked coil. Molecules of hyaluronan start to entangle already at concentrations of less than 1 g/l and form a continuous polymer network. Some of the functions of the polysaccharide have been connected with the unique physical chemical characteristics of the network such as its rheological properties, flow resistance, osmotic pressure, exclusion properties and filter effect. Hyaluronan is synthesized in the cell membrane by adding monosaccharides to the reducing end of the chain. The precursors are UDP-glucuronic acid and UDP-N-acetylglucosamine. The polysaccharide grows out from the cell surface and it can be shown that fibroblasts, for example, surround themselves with a coat of hyaluronan. The rate of biosynthesis is regulated by various factors, such as growth factors, hormones, inflammatory mediators, etc. The responsible enzyme, hyaluronan synthase, is a phosphoprotein and the regulation of the synthetic rate is apparently via phosphorylation. The hyaluronan is at least partly carried by lymph flow from the tissues. Part of the material is taken up and degraded in the lymph nodes. Another part is carried to the general circulation and taken up in the endothelial cells in the liver sinusoids. These cells have specific receptors for hyaluronan, which also recognize chondroitin sulphate. The uptake in the liver of high-molecular weight hyaluronan is very efficient and its normal half-life in serum is only in the order of 2 to 5 min. The polysaccharide is rapidly degraded in the lysosomes to low-molecular weight products, lactate and acetate. The total turnover of hyaluronan in serum is in the order of 10-100 mg/24 h. The normal concentration of hyaluronan in serum is less than 100 micrograms/l with a mean of 30-40 micrograms/l. High serum levels have been noted in liver cirrhosis (impaired uptake in the liver) and rheumatoid arthritis (increased synthesis in the tissues). Hyaluronan has been shown to interact specifically with certain proteins and cell surfaces. It binds to proteoglycans in cartilage and other tissues and fills an important structural role in the organization of the extra-cellular matrix.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Biochemistry of hyaluronan. 312 95

7 alpha-Hydroxylation of cholesterol is a stereospecific reaction consisting of the replacement of the 7 alpha-hydrogen with a hydroxyl group. When cholesterol labeled with tritium at the 7 alpha position is administered, the hydroxylation of the substrate will result in the loss of tritium which in turn will label the body water. The rate of tritium enrichment of the body water could thus give a quantitative estimate of the hydroxylation rate. This study describes the validation of the procedure with some 21 studies performed on 15 subjects in different conditions. [7 alpha-3H]cholesterol was administered intravenously in 50 ml of plasma and thereafter blood was sampled at timed intervals for 4 to 5 days. The rate of the hydroxylation of cholesterol was calculated from the time course of the specific activities of plasma cholesterol and body water after tracer administration and was expressed as 7 alpha-hydroxycholesterol formed/24 hr. Calculated values of hydroxylation in three control subjects (493 +/- 206), five patients with hyperlipoproteinemia (539 +/- 168), and seven cirrhotic patients (153 +/- 136) are in good agreement with figures reported for bile acid synthesis determined with other techniques. Cholesterol 7 alpha-hydroxylation rate is reduced in patients with cirrhosis, the impairment being related to the severity of the disease. Cholestyramine administered to one subject for 4 weeks produced a threefold increase of the hydroxylation. Administration of chenodeoxycholic acid resulted in a 50% decrease, whereas that of ursodeoxycholic did not produce consistent changes of the hydroxylation rate. The results support the current view that 7 alpha-hydroxylation of cholesterol is rate-limiting in the synthesis of bile acids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo evaluation of cholesterol 7 alpha-hydroxylation in humans: effect of disease and drug treatment. 355 91

Erythrocytes from alcoholics with and without liver cirrhosis and from rats treated either with ethanol or thioacetamide, the latter treatment resulting in hepatic fibrosis, were analysed for their membrane fatty acid composition and their susceptibility to lipid peroxidation. Red cells containing less arachidonic acid than controls, as found in alcoholics with liver cirrhosis, were less susceptible to lipid peroxidation than controls. This observation was confirmed by experiments with rat erythrocytes obtained from animals with hepatic fibrosis. However, red cells containing less linoleic acid than controls, as found in alcoholics without liver cirrhosis, exhibited a normal degree of lipid peroxidation upon oxidant stress induced by hydrogen peroxide. The results demonstrated that in red cells only fatty acids with four double bonds seem to be involved in membrane peroxidation reactions under the condition chosen. This observation might be of relevance for in vivo aging of red cells.
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PMID:Alcohol consumption and hepatic fibrosis affect the fatty acid composition of red blood cells and their susceptibility to lipid peroxidation. 361 38

Red blood cells from alcoholics with and without liver cirrhosis and control subjects were examined for the susceptibility to lipid peroxidation. Red blood cells of patients with liver cirrhosis were found to be less sensitive to hydrogen peroxide-induced peroxidation measured by a new, reliable and sensitive method: the release of pentane during red blood cell lipid peroxidation. Changes of sensitivity to lipid peroxidation correlated with the severity of the liver malfunction, but not with abnormalities of the lipid composition of red cell membranes which are apparent in patients with liver disease. In alcoholics without liver cirrhosis, only minor changes in the susceptibility of red cells to peroxidation were observed.
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PMID:Decreased susceptibility of red blood cells to lipid peroxidation in patients with alcoholic liver cirrhosis. 398 30

A new solid phase enzyme-linked immunosorbent assay (ELISA) was developed for the quantitation of human protein C antigen. Anti-protein C F(ab')2 fragments were adsorbed to polystyrene plates. The binding of serial dilutions of control or test plasma, containing protein C, was detected by incubation with peroxidase-labeled anti-protein. C-IgG followed by the addition of hydrogen peroxyde and 0-phenylenediamine. This ELISA is specific, sensitive (detection limit: 0.02%) and accurate (variation coefficient: 3 to 10%). When results are compared to those obtained by the Laurell technique (electroimmunodiffusion, EID), the correlation coefficient is 0.95 in all tested plasmas. Protein C antigen was measured by ELISA and EID in plasma from 40 controls, 14 patients with congenital protein C deficiency, 15 patients with liver cirrhosis and 40 dicoumarol-treated cases. In normal plasma, protein C ranged from 70 to 126%. In congenital deficiency, protein C was between 35 and 58% in 13 cases and 9% in one of them. In patients with liver cirrhosis and dicoumarol-treated cases, levels of protein C antigen were compared to those of other vitamin K dependent factors, i.e. Factors II and IX measured by EID and Factor X assayed by EID and ELISA. In liver cirrhosis, the amount of protein C was significantly lower than that of Factors II, IX and X. In short-term and long-term dicoumarol-treated patients, the highest correlation (r = 0.72) was observed between protein C and Factor X levels. In the plasma of patients undergoing oral anticoagulant therapy, protein C decreased more rapidly than Factors X or II and migrated in presence of calcium as a double peak, one with a normal mobility and one more anodal corresponding to the non carboxylated form of protein C.
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PMID:A new method for the estimation of protein C by ELISA. 608 75

To test whether impaired carbohydrate tolerance in cirrhosis could be modified by dietary means ten cirrhotic patients, five of them taking insulin, took as breakfast either lentils or wholemeal bread and cottage cheese containing the same amount of carbohydrate and protein. Lentils resulted in significantly diminished blood glucose, insulin (in those not on insulin) and gastric inhibitory peptide responses. Enteroglucagon and neutrotensin levels were high with lentils, suggesting that absorption of lentil carbohydrate continued into the ileum with perhaps some malabsorption, so confirming the results of earlier studies in vitro. However, breath hydrogen studies on a separate group of eight healthy volunteers indicated that the difference in carbohydrate malabsorption between lentil, and wholemeal bread was insignificant. It is suggested that slowly digested carbohydrate foods, such as leguminous seeds, may minimize carbohydrate intolerance in patients with cirrhosis.
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PMID:Slowly digested carbohydrate food improves impaired carbohydrate tolerance in patients with cirrhosis. 632 39

Ther are several main mechanisms that allow us to understand a number of the hepatic and metabolic effects of ethanol. Ethanol is oxidized in the liver to two products (hydrogen and acetaldehyde), to which many of the effects of ethanol can be attributed. The hydrogen generated alters the redox state, and though this effect is attenuated after chronic ethanol consumption, it may still be sufficient to explain alterations in lipid metabolism, possibly increased collagen deposition, and, under special circumstances, depression of protein synthesis. Acetaldehyde impairs microtubules, decreases protein secretion, and causes protein retention and ballooning of the hepatocyte. Acetaldehyde exerts toxicity also with regard to other key cellular functions, particularly in the mitochondria, and it may promote peroxidation of the cellular membranes. It is noteworthy that after chronic consumption of ethanol, there is increased acetaldehyde, in part because of decreased disposition in the mitochondria and partly because of induction of an alternative pathway of ethanol metabolism, namely the microsomal ethanol-oxidizing system. Indeed, this MEOS increases in activity after chronic ethanol consumption, with cross induction and acceleration of the metabolism of other drugs and increased lipoprotein production with hyperlipemia. There is also increased microsomal activation of hepatotoxic compounds (including drugs and possibly vitamin A). Fibrosis and cirrhosis can develop despite an associated adequate diet and even in the absence of alcoholic hepatitis. They are preceded by myofibroblasts and fibroblast proliferation. What eventually causes the increased number of myofibroblasts and promotes fibrosis is unclear, nor do we know the relative role of hepatocytes or mesenchymal cells in the process of fibroplasis. Possibly selective roles in this process of specific nutritional factors remain to be elucidated.
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PMID:Alcohol, protein nutrition, and liver injury. 634 74

The gut microfloral metabolism of sorbitol and lactulose was investigated in 10 healthy control subjects and 10 patients with cirrhosis of the liver, by measuring the pulmonary excretion of the fermentational gases hydrogen and methane during 3 h. A possible acute effect on venous plasma ammonia after a single dose of sorbitol or lactulose was also investigated. No significant difference in fermentation gas excretion was found after ingestion of sorbitol compared with lactulose in healthy controls or cirrhotic patients (p greater than 0.05). Neither sorbitol nor lactulose had significant effect on plasma ammonia concentrations during the first 3 h after ingestion. These findings indicate that both sorbitol and lactulose are extensively fermented by the colonic flora and that the possibility of replacing lactulose with the much cheaper sorbitol in the treatment of portal-systemic encephalopathy ought to be investigated. The suggested acute gut-ammonia trapping effect of lactulose caused by acidification of the gut lumen from fermentative end-products was not supported by the present findings.
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PMID:Pulmonary hydrogen and methane and plasma ammonia after the administration of lactulose or sorbitol. 667 60

Sera from 9 persons with either biopsy-proven alcoholic liver disease or a history of chronic, excessive ethanol consumption were analyzed for their content of various hydrolases. Compared to controls, significant elevations in the following enzyme activities were seen in sera from the patient population: acid phosphatase (2.0-fold), beta-glucuronidase (2.1-fold), hexosaminidase (1.4-fold), and alpha-L-fucosidase (2.3-fold). In addition, alpha-mannosidase activity, previously reported to be unchanged in cases of hepatic cirrhosis [Reglero et al., Clinica chim. Acta 130: 155-158], (1980) was found to be significantly increased (p less than 0.001) when assays were performed at acid (pH 4.5) or intermediate (pH 5.5) hydrogen ion concentrations. Fractionation of sera on DEAE-Sephadex columns showed that the increase in alpha-mannosidase activity in the serum of patients with alcoholic liver disease was due to increases in the level of at least one 'acid alpha-mannosidase' and two intermediate pH optimum alpha-mannosidases. The general increase in the activity of a group of glycosidases is consistent with a hypothesis involving decreased clearance of glycoproteins from the blood of persons with hepatic cirrhosis.
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PMID:Serum alpha-mannosidase in patients with alcoholic liver disease. 671 94

Esophago-gastric hemodynamics subsequent to devascularization was studied in a view of changes in mucosal blood flow and tissue oxygen tension (PtO2). Thirty-four mongrel dogs (26 normal dogs and 8 portal hypertensive dogs) were used in experimental studies, and mucosal blood flow was determined by means of hydrogen gas clearance. Remarkable reduction of a 73% in gastric cardia was recognized on normal dogs just after extended devascularization, and those dogs died of severe gastric necrosis within 4 days after surgery. Reduction of a 28.5% in the cardia was found by the devascularization on portal hypertensive dogs produced by a whole liver compression. These portal hypertensive dogs survived for 2 weeks after surgery, and then mucosal blood flows were returned to the previous levels. Liver cirrhosis (10 cases) with esophageal varices were used for clinical studies. Gastric hemodynamics was measured by PtO2 before and after devascularization. Reduction of a 25.7% in the cardia was recognized on cirrhotic patients. These results suggest that influences of extended devascularization on esophago-gastric hemodynamics would be a small in cirrhotic patients with esophageal varices.
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PMID:[Experimental and clinical studies on esophago-gastric hemodynamics before and after devascularization for esophageal varices]. 674 7


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