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)

Protein undernutrition, alterations of hormones such as IGF-1, testosterone and cortisol, and increased lipid peroxidation-which may be related with deranged metabolism of some elements such as iron (Fe), zinc (Zn), manganese (Mn), selenium (Se) or copper (Cu)-may contribute to muscle damage in non alcoholic cirrhosis. Here, we analyse the effect of protein deficiency on muscle Cu, Fe, Zn, Mn and Se in carbon-tetrachloride (CCl(4)) induced liver cirrhosis. We also study the association between protein undernutrition and these trace elements with the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products, and how all these are related with muscle morphological changes in 40 male adult Sprague-Dawley rats. Liver cirrhosis was induced by intraperitoneal injection of CCl(4) to 10 rats fed a 2% protein diet, and to another 10 fed a 18% protein control diet. Two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. After sacrifice (6 weeks later), we found type IIa fibre atrophy in the cirrhotic animals, especially in the low-protein fed ones and this was due to protein deficiency. Muscle Fe increased in low protein fed cirrhotic rats. No relationship was found between muscle changes and any of the hormones, enzymes and trace elements analysed, or with liver fibrosis. These results suggest that muscle atrophy observed in CCl(4)-induced cirrhosis is related with protein deficiency, but not with cirrhosis itself.
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PMID:Protein deficiency and muscle damage in carbon tetrachloride induced liver cirrhosis. 1456 4

Apart from increased blood ammonia, alterations in various other substances have been implicated in the pathogenesis of hepatic encephalopathy (HE). The role of trace elements like zinc and manganese has been described recently. Zinc is an essential trace element and functions as an antioxidant. Low zinc concentrations have been reported in patients with cirrhosis of the liver, particularly those with HE. Patients with fulminant hepatic failure and subacute hepatic failure have also been shown to have low serum zinc levels. In animal experiments, zinc supplementation leads to a reduction in blood ammonia. Zinc deficiency also leads to alteration of neurotransmitters like gamma aminobutyric acid and norepinephrine. Zinc supplementation has been tried in HE. It may have a role in mild chronic HE, though further trials are necessary. Increased serum manganese levels have been shown in acute and chronic hepatitis, cirrhosis and congenital disorders like Alagille's syndrome. High manganese content has been reported in the globus pallidus in animals as well as brain tissues of patients dying of HE. Miners with chronic manganese exposure have encephalopathy and extra-pyramidal features similar to HE. It has been postulated that manganese impairs neuronal oxidative metabolism. The role of manganese in the pathogenesis of HE and the possibility of its chelation as treatment need further study.
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PMID:Role of trace elements in hepatic encephalopathy: zinc and manganese. 1502 50

Hepatic encephalopathy (HE) is a potentially reversible neuropsychiatric syndrome secondary to cirrhosis and other severe liver diseases. Magnetic resonance imaging (MRI) and MR spectroscopy (MRS) have been explored to provide new insight into the pathophysiology, diagnosis and treatment of HE. MRI shows brain atrophy especially in the frontal region. Globus pallidus, putamen and portions of the internal capsule appear hyperintense on T1-weighted images; this is likely to be due to deposition of manganese as a result of portosystemic shunting and liver dysfunction. MRS permits the detection and quantification of certain brain metabolites in vivo. There is decrease in myoinositol and choline concentrations and increase in glutamine concentrations. There is no change in n-acetyl-aspartate. Depletion of myoinositol is the most sensitive and specific spectroscopic marker in HE. Its loss is most likely a compensatory mechanism for the accumulation of glutamine. In conclusion, MRI and MRS examine different aspects of hepatocerebral disease.
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PMID:Magnetic resonance imaging and spectroscopy in hepatic encephalopathy. 1502 55

Nonalcoholic fatty liver disease, frequently associated with obesity, can lead to nonalcoholic steatohepatitis (NASH) and cirrhosis. The pathophysiology of NASH is poorly understood, and no effective treatment is available. In view of a potential deleterious role for reactive oxygen species (ROS), we investigated the origin of ROS overproduction in NASH. Mitochondrial production of ROS and its alterations in the presence of antioxidant molecules were studied in livers from ob/ob mice that bear a mutation of the leptin gene and develop experimental NASH. N-acetyl-cysteine and the superoxide dismutase (SOD) mimics ambroxol, manganese [III] tetrakis (5,10,15,20 benzoic acid) (MnTBAP), and copper [II] diisopropyl salicylate (CuDIPS) were used to target different checkpoints of the oxidative cascade to determine the pathways involved in ROS production. Liver mitochondria from ob/ob mice generated more O(2)*- than those of lean littermates (P <.01). Ex vivo, all three SOD mimics decreased O(2)*- generation (P <.001) and totally inhibited lipid peroxidation (P <.001) versus untreated ob/ob mice. Those modifications were associated with in vivo improvements: MnTBAP and CuDIPS reduced weight (P <.02) and limited the extension of histological liver steatosis by 30% and 52%, respectively, versus untreated ob/ob mice. In conclusion, these data demonstrate deleterious effects of superoxide anions in NASH and point at the potential interest of nonpeptidyl mimics of SOD in the treatment of NASH in humans.
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PMID:Pivotal role of superoxide anion and beneficial effect of antioxidant molecules in murine steatohepatitis. 1512 56

HE is a serious complication of alcoholic liver disease that contributes to cognitive dysfunction in chronic alcoholic patients. In patients with HE, the damaged liver can no longer remove neurotoxic substances such as ammonia and manganese from the blood. As a result, these molecules may enter the brain, where they can exert a variety of harmful effects that interfere with normal neurotransmitter activity, impair motor functions, and cause structural alterations in the astrocytes. To prevent or treat HE in alcoholic patients with cirrhosis, physicians currently rely primarily on strategies to lower blood ammonia concentrations as well as on liver transplantation in patients with end-stage liver disease; new approaches also are also being investigated.
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PMID:Hepatic encephalopathy--a serious complication of alcoholic liver disease. 1530 24

Hepatic encephalopathy (HE) is a brain disorder caused by chronic liver failure, particularly in alcoholics with cirrhosis, which results in cognitive, psychiatric, and motor impairments. In these patients, the number of functional liver cells is reduced, and some blood is diverted around the liver before toxins are removed. As a result, toxins such as ammonia and manganese can accumulate in the blood and enter the brain, where they can damage nerve cells and supporting cells called astrocytes. Positron emission tomography analyses have determined that ammonia levels are elevated in the brains of HE patients; ammonia accumulation can alter the expression of various important brain genes. Magnetic resonance images show that manganese is deposited in a brain area called the globus pallidus; manganese deposits may be responsible for structural changes in the astrocytes that are characteristic of HE. Treatment of patients with HE involves measures to lower ammonia levels in the blood, medications to counteract ammonia's effects on brain cell function, devices to compensate for liver dysfunction, and liver transplantation.
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PMID:Hepatic encephalopathy. 1553 52

Intestinal failure-associated liver disease develops in 40% to 60% of infants who require long-term total parenteral nutrition (TPN) for intestinal failure and 15% to 40% of adults on home parenteral nutrition. The clinical spectrum includes hepatic steatosis, cholestasis, cholelithiasis, and hepatic fibrosis. Progression to biliary cirrhosis and the development of portal hypertension and liver failure occurs in a minority but is more common in infants and neonates than in adults. The pathogenesis is multifactorial. In infants it is related to prematurity, low birth weight, duration of PN, short bowel syndrome requiring multiple laparotomies, and recurrent sepsis. Other important mechanisms include lack of enteral feeding, which leads to reduced gut hormone secretion; reduction of bile flow and biliary stasis, which leads to the development of cholestasis; and biliary sludge and gallstones, which exacerbate hepatic dysfunction. In adults, IFALD is less common and related to age, length of time on PN, total caloric intake, and lipid or glucose overload. In preterm infants, a deficiency of taurine or cysteine may play a role, whereas in both adults and children, choline deficiency may exacerbate IFALD. Lipid emulsions, choline deficiency, and manganese toxicity are associated with both hepatic steatosis and cholestasis in adults and children. Management strategies for the prevention of intestinal failure-induced liver disease include early enteral feeding, a multidisciplinary approach to the management of parenteral nutrition, and aseptic catheter techniques to reduce sepsis. The addition of choline, taurine, and cysteine to PN solutions may also play a role. Oral administration of ursodeoxycholic acid may improve bile flow and reduce gallbladder stasis. Survival after either isolated small bowel or combined liver and small bowel transplantation is approximately 50% at 5 years, making this an acceptable therapeutic option in adults and children with irreversible liver and intestinal failure.
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PMID:Intestinal failure-associated liver disease: what do we know today? 1647 75

Ammonium and manganese are neurotoxic agents related to brain metabolic disturbances observed after prolonged liver damage. The aim of this study was to assess the production of nitric oxide (NO) in the brain of cirrhotic rats exposed to manganese. We induced cirrhosis by bile duct ligation for 4 weeks in rats. From brain, striatum and globus pallidus were dissected out, and NO synthase activity and the content of nitrites plus nitrates (NOx) were determined. In pallidum we found a diminished constitutive NO synthase activity from cirrhotic rats, independently of manganese exposure. This result was confirmed by low levels of NOx in the same brain area (P<0.05, two-way ANOVA). This finding was not related to protein expression of NO synthase since no differences were observed in immunoblot signals between cirrhotic and sham-operated animals. Results from present study suggest that the production of NO is reduced in basal ganglia during cirrhosis.
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PMID:Nitric oxide production in striatum and pallidum of cirrhotic rats. 1647 92

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome due to hepatic dysfunction and porto-systemic shunting of the intestinal blood. Cirrhosis is the most frequent liver disease causing HE. On most occasions, HE appears due to a superimposed precipitating factor (gastrointestinal bleeding, infections, renal and electrolyte disturbances, etc.). Ammonia produced in colon by intestinal bacteria is the main toxic substance implicated in the pathogenesis of HE. Other mechanisms, such as changes in the GABA-benzodiazepine system, accumulation of manganese into the basal ganglia of the brain, changes in blood-brain barrier and neurotransmission disturbances are also present. Clinical manifestations of HE may vary widely, from minimal neurologic changes, only detected with specific tests, to deep coma. Treatment of HE should be directed to controlling the precipitating factors, as well as therapies aimed at correcting the above-mentioned pathophysiological changes, mainly reduction of blood ammonia levels. Artificial liver support systems may play a role in the future. Liver transplantation should be evaluated as a definitive therapy in all cases of HE.
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PMID:Hepatic encephalopathy: from pathophysiology to treatment. 1649 56

The role of trace elements in the pathogenesis of liver cirrhosis and its complications is still not clearly understood. Serum concentrations of zinc, copper, manganese and magnesium were determined in 105 patients with alcoholic liver cirrhosis and 50 healthy subjects by means of plasma sequential spectrophotometer. Serum concentrations of zinc were significantly lower (median 0.82 vs. 11.22 micromol/L, p < 0.001) in patients with liver cirrhosis in comparison to controls. Serum concentrations of copper were significantly higher in patients with liver cirrhosis (median 21.56 vs. 13.09 micromol/L, p < 0.001) as well as manganese (2.50 vs. 0.02 micromol/L, p < 0.001). The concentration of magnesium was not significantly different between patients with liver cirrhosis and controls (0.94 vs. 0.88 mmol/L, p = 0.132). There were no differences in the concentrations of zinc, copper, manganese and magnesium between male and female patients with liver cirrhosis. Only manganese concentration was significantly different between Child-Pugh groups (p = 0.036). Zinc concentration was significantly lower in patients with hepatic encephalopathy in comparison to cirrhotic patients without encephalopathy (0.54 vs. 0.96 micromol/L, p = 0.002). The correction of trace elements concentrations might have a beneficial effect on complications and maybe progression of liver cirrhosis. It would be recommendable to provide analysis of trace elements as a routine.
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PMID:Serum concentration of zinc, copper, manganese and magnesium in patients with liver cirrhosis. 1705 18


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