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)

Liver cell functional heterogeneity has been shown to persist in toxic CCl4 cirrhosis in growing rats, but the zonation observed in cirrhotic nodules may be different in other types of cirrhosis. To investigate this possibility, we looked at the zonal activities of two microsomal enzymes, glucose-6-phosphatase and NADPH dehydrogenase, in cirrhotic nodules from growing rats with chronic cholestasis. Zonal activities were measured by quantitative cytochemistry and microdensitometry. Liver cell heterogeneity was demonstrated, and we confirmed that the metabolic zonation is the mirror image of that observed in toxic cirrhosis, with periportal activity at the nodule periphery and perivenular activity at the nodule centers. Glucose-6-phosphatase activity was 2.06 times higher at the peripheries of the nodules than at the centers, whereas NADPH dehydrogenase activity at the nodule periphery was 72% of the nodule center activity. We conclude that a liver cell functional heterogeneity persists in biliary rat cirrhosis, with zonation the reverse of that previously found in toxic CCl4 cirrhosis.
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PMID:Liver metabolic zonation in rat biliary cirrhosis: distribution is reverse of that in toxic cirrhosis. 131 72

To evaluate whether liver metabolic zonation persists in human biliary cirrhosis, we used quantitative cytochemistry to measure activities of glucose 6 phosphatase (G6P) and NADPH dehydrogenase (ND) in hepatocytes situated in different zones of liver cirrhotic nodules. Liver specimens were obtained from 13 children with extrahepatic biliary atresia with compensated cirrhosis. Activity and distribution were compared with zonal activities measured in 17 control human liver specimens obtained during reduction hepatectomies for orthotopic liver transplantation. In normal human liver, G6P was 1.86 times more active in the periportal than in the perivenular zone. On the contrary, ND activity was lower in the periportal zone (63% of perivenular activity). A metabolic zonation persisted in extra-hepatic biliary atresia with compensated cirrhosis. G6P activity was 1.56 times greater at the nodule periphery than at the nodule center, whereas ND activity was lower at the periphery (75% of nodule center activity). This metabolic zonation is the opposite of that observed in animal toxic (CCl4) cirrhosis, in which greater G6P activity is observed at the nodule center and greater ND activity at its periphery. This confirms our previous hypothesis that the type of cirrhotic metabolic zonation may depend on the site of initial liver damage.
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PMID:Persistence of a liver metabolic zonation in extra-hepatic biliary atresia cirrhotic livers. 165 19

To evaluate changes in liver metabolic zonation during development of juvenile cirrhosis, zonal activities of succinate dehydrogenase, glutamate dehydrogenase, glucose-6-phosphatase, and nicotinamide adenine dinucleotide phosphate (NADPH) dehydrogenase were measured by quantitative cytochemistry in the liver of developing rats intoxicated with carbon tetrachloride and phenobarbitone. During treatment, activities were most decreased in perivenular zones and subsequently at the periphery of the cirrhotic nodules for succinate dehydrogenase and glucose-6-phosphatase, whereas glutamate dehydrogenase and NADPH dehydrogenase were less affected. In the periportal zones, enzyme activities decreased less. After stopping intoxication, the rats remained cirrhotic, but enzyme activities returned to control perivenular levels at the periphery of the cirrhotic nodule and to control periportal levels at its center. It is concluded that a metabolic zonation persists in carbontetrachloride/phenobarbitone-induced juvenile cirrhosis and that enzyme activities can recover despite persisting cirrhosis. In this model, afferent vessels seem to be located at the center of the cirrhotic nodules, and efferent vessels, at their periphery. A different metabolic zonation may exist in other human and animal liver cirrhosis that could be related to the site of initial liver damage.
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PMID:Adaptative changes of metabolic zonation during the development of cirrhosis in growing rats. 216 52

We previously described a long-lasting overproduction of nitric oxide (NO) in cirrhotic patients with spontaneous bacterial peritonitis. The aim of the present study was to investigate the presence of the inducible NO pathway in peritoneal macrophages. Ascitic fluids were collected from 29 patients with cirrhosis, aged between 35 and 82 years. Peritoneal macrophages were isolated and cultured in the presence or absence of 1 microg/ml lipopolysaccharide and/or 500 units/ml interferon-gamma (IFN-gamma) for 6 days. NO production was measured as nitrate+nitrite (NO(x)), inducible NO synthase (iNOS) protein expression was analysed by immunocytochemistry and Western blot analysis using a specific anti-(human iNOS) antibody, and the catalytic activity of NOS was revealed by cytochemical staining for NADPH-dependent diaphorase. Cultured macrophages spontaneously released small amounts of NO(x) [median (10-90th percentile) of 18 separate experiments: 3.3 (0-8) micromol/l]. Addition of lipopolysaccharide alone or in combination with IFN-gamma to the culture medium did not change the levels of NO(x), while IFN-gamma alone dramatically increased NO production [13.4 (3.5-28.3) micromol/l; P<0.001]. Macrophages were stimulated by IFN-gamma to a greater extent in patients with recent spontaneous bacterial peritonitis (n=13) than in those in a stable clinical condition (n=18) [19.8 (10.5-30.1) and 10.0 (3.2-14.5) micromol/l respectively; P<0.001]. Macrophages freshly isolated or stimulated with IFN-gamma expressed iNOS protein, as shown by Western blot and immunocytochemical analysis, and stained for NADPH diaphorase. Our findings demonstrate the presence of iNOS protein in peritoneal macrophages from cirrhotic patients. The role of IFN-gamma appears to be a determinant for the up-regulation of NO production, particularly under conditions of infection. Therefore peritoneal macrophages producing large amounts of NO at the site of infection may contribute to maintaining splanchnic vasodilation in these patients.
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PMID:Up-regulation of nitric oxide production by interferon-gamma in cultured peritoneal macrophages from patients with cirrhosis. 1049 39

AIM:To observe the nitric oxide synthase (NOS) distribution in the esophageal mucosa and hemodynamic changes in cirrhotic rats.METHODS:NOS distribution in the lower esophagus of rats with carbon tetrachloride-induced cirrhosis was assessed by using NADPH-diaphorase (NADPH-d) histochemical method.Concentration of NO in serum were measured by fluorometric assay. Mean arterial pressure (MAP), cardiac output (CO), cardiac index (CI), splanchnic vascular resistance (SVR), and splanchnic blood flow (SBF) were also determined using (57)Co-labled microsphere technique.RESULTS:Intensity of NOS staining in the esophageal epithelium of cirrhotic rats was significantly stronger than that in controls. There was a NOS-positive staining area in the endothelia of esophageal submucosal vessels of cirrhotic rats, but the NOS staining was negative in normal rats. NO concentration of serum in cirrhotic rats were significantly higher in comparison with that of controls. Cirrhotic rats had significantly lower MAP, SVR and higher SBF than those of the controls.CONCLUSION:Splanchnic hyperdynamic circulatory state was observed in rats with cirrhosis. The endogenous NO may play an important role in development of esophageal varices and in changes of hemodynamics in cirrhosis.
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PMID:Nitric oxide synthase distribution in esophageal mucosa and hemodynamic changes in rats with cirrhosis. 1181 32