Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Long-Evans Cinnamon (LEC) rats, an inbred strain of a mutant rat isolated from Long-Evans rats, develop hereditary hepatitis. To elucidate the role of copper metabolism in the development of the hepatitis in LEC rats, we examined the copper concentration in the tissues and serum levels of copper and ceruloplasmin. Copper concentration in the liver of LEC rats was over 40 times that of normal Long-Evans Agouti (LEA) rats, while the serum ceruloplasmin and copper concentrations in LEC rats decreased significantly. The hepatocytes of LEC rats show steatosis in cytoplasm and pleomorphism of mitochondria, resembling the histologic features of the liver in Wilson's disease. These findings suggest that the hereditary hepatitis in LEC rats is closely associated with copper toxicity, and may be dealing with a rat form of Wilson's disease. Thus the LEC rats will provide a unique and useful animal model for clarifying the mechanism and for developing treatment strategies for Wilson's disease and other abnormal copper metabolism in humans.
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PMID:Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease. 202 51

Serum Zn2+, Cu2+, and Mg2+ were assayed in patients with chronic persisting hepatitis HBsAg-positive. Significantly decreased serum magnesium with increased serum copper levels were noted.
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PMID:[Trace elements: zinc, copper and magnesium in patients with chronic persisting hepatitis--evaluation of changes during therapy]. 208 28

The study of chronic liver disease has been hampered by insufficient information relative to the pathogenesis of the many forms of hepatitis. Consequently, well-designed treatment strategies are frequently lacking. Wilson's disease is characterised by excessive copper accumulation in the liver and other organs. While d-penicillamine is clearly effective, many patients may not tolerate its many adverse effects. Trientine, oral zinc and unithiol have all shown promise as therapeutic alternatives. Autoimmune chronic active hepatitis responds well to prednisone and azathioprine. Cyclosporin has also produced clinical improvement in several case reports but no comparison has yet been made with the current standard therapy. Recombinant interferon-alpha (IFN alpha) has demonstrated the ability to inhibit hepatitis B viral replication, and the combination of oral corticosteroids followed by IFN alpha is more effective than either agent alone in eliminating viral replication in patients with chronic active hepatitis B. Currently, primary sclerosing cholangitis (PSC) has no standard medical management, but corticosteroids and methotrexate may each have a future role in its treatment. Drug treatment for primary biliary cirrhosis (PBC) has been disappointing, and early reports of success with d-penicillamine were not confirmed in large well-controlled trials. While some reports of improvement with several agents have been described, larger studies are still needed. Alcoholic liver disease continues to be associated with significant morbidity and mortality and numerous investigators have researched several different medical avenues of treatment. Success reported with androgens and the antithyroid agent propylthiouracil in alcoholic liver disease will need confirmation by other research before these agents can be recommended for routine use. Finally, colchicine may prove to be effective in slowing the rate of fibrosis in cirrhosis, but this has yet to be conclusively proven.
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PMID:Current therapy of chronic liver disease. 219 64

In unseparated human blood the reactivity of yeast copper (I)-thionein on TPA-activated polymorphonuclear leukocytes was evaluated and compared with low Mr copper chelates exerting Cu2Zn2 superoxide dismutase mimetic activity. Cu, 18 microM, in the form of Cu-thionein was sufficient to inhibit the superoxide production of activated human blood phagocytes by 50%. Furthermore, the scavenging of hydroxyl radicals and singlet oxygen by Cu(I)-thionein was determined, using the 2-deoxyribose fragmentation assay induced by decaying K3CrO8 and the NADPH oxidation caused by UVA illuminated psoralen, respectively. The inhibitory reactivity of Cu-thionein in both assays was compared with that of serum proteins including albumin, ceruloplasmin, transferrin, and ferritin. The galactosamine/endotoxin-induced hepatitis in male NMRI mice was used to evaluate the antiinflammatory reactivity of Cu-thionein in vivo. The serum copper, superoxide dismutase, and sorbitol dehydrogenase concentrations, as well as the activity of polymorphonuclear leukocytes in unseparated blood seemed most appropriate to quantify the protective capacity of Cu-thionein in the course of an oxidative stress-dependent liver injury. The intraperitoneal application of 32.5 mumols/kg thionein-Cu limited this damage to 45%.
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PMID:Antiinflammatory reactivity of copper(I)-thionein. 224 84

Hepatolenticular degeneration (Wilson's disease) is a hereditary disease in which metabolic disorder of copper leads to its accumulation in the liver, brain, cornea and kidneys with consequent pathologic changes in those organs. Hereditary mechanism of the disease is autosomal recessive with prevalence of 30-100 per 1,000,000 inhabitants. Etiology of this disease is not yet explained. There are two hypotheses. The first one is that it is the disorder of ceruloplasmine metabolism caused by insufficient synthesis of normal ceruloplasmine, or synthesis of functionally abnormal ceruloplasmine. The second one is: the block of copper biliar excretion which is the consequence of the liver lysosomes functional defect. Pathogenetic mechanism of disease is firstly long-term accumulation of copper in the liver, and later, when the liver depo is full, its releasing in circulation and accumulation in the brain, cornea, kidneys and bones, which causes adequate pathologic changes. Toxic activity of copper is the consequence of its activity on enzymes, particularly on those with -SH group. There are two basic clinical forms of the disease: liver disease or neurologic disease. Before puberty the liver damage is more frequent, while in adolescents and young adults neurologic form of the disease is usual. The liver disease is nonspecific and characterized by symptoms of cirrhosis and chronic aggressive hepatitis. The only specificity is hemolytic anemia which, in combination with previous symptoms, is important for diagnosis of the disease. Neurologic symptoms are the most frequent consequence of pathologic changes in the basal ganglia. In our patients the most frequent symptoms were tremor (63%); dysarthria, choreoathetosis and rigor (38%); ataxia and mental disorders (31%); dysphagia and dystonia (12%), diplopia, hypersalivation, nystagmus and Babinski's sign (6%). Among pathologic changes in other tissues and organs the most important is the finding of Kayser-Fleischer ring in the cornea as a result of copper accumulation. Its importance for precise diagnosis is great. The diagnosis of the disease is based on anamnesis, clinical examination, specific and nonspecific laboratory tests. The therapy of choice is penicillamine. If we use it early, the result will be good remission in the majority of patients. Late diagnosis or delay in treatment cause death which is the result of bleeding from esophageal varices or basal ganglia disease. Immunologic damages caused by penicillamine demand interruption of therapy and substitution by three-ethyl-tetra-amine (TETA). We also use zinc salts and tetratiomolibdate in therapy of this disease. Pathogenesis, clinical picture and therapy of the disease are based on our own results.
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PMID:[Hepatolenticular degeneration]. 226 49

Histomorphologic, histochemical, and atomic absorption analysis studies were performed on liver tissue from 623 clinically normal purebred and mixed-breed dogs to assess the range of hepatic copper concentrations, the histologic distribution of copper, and the histomorphologic changes associated with the various copper concentrations that were found. Atomic absorption analysis revealed a continuous numerical spectrum ranging from less than 100 parts per million on a dry weight basis (ppm dw) to more than 2,000. No decisive numerical criterion was found that could be used to separate normal from abnormal copper concentrations because of this continuous array. The threshold for histochemical demonstration of copper-containing granules using rhodanine or rubeanic acid staining was 400 ppm dw. At this concentration the copper-containing granules were located in the centrilobular hepatocytes (zone 3 of Rappaport). Copper-containing granules were found in the midzonal and periportal hepatocytes (zones 2 and 1 of Rappaport) in livers with 1,000 ppm dw and higher copper concentrations. The majority of the 623 livers were normal histomorphologically. Multifocal hepatitis characterized by mixed inflammatory cell accumulation and centrilobular distribution was found to be associated with copper concentrations in the range of 2,000 ppm dw or higher. An appropriate upper limit for normal hepatic copper concentration in the dog was not determined based on the present study.
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PMID:Hepatic copper concentrations in purebred and mixed-breed dogs. 234 41

Eleven cases of Wilson's disease presenting as fulminant hepatic failure were analysed retrospectively to determine the specificity or otherwise of the histological findings. All cases were cirrhotic, eight with a micronodular pattern. There was marked parenchymal collapse with ductular proliferation and mild inflammation. Other features included cholestasis, hepatocyte necrosis, microvesicular fat and nuclear vacuolation. Orcein staining demonstrated copper-associated protein in the periphery of cirrhotic nodules in all cases and also variably within nodules in eight cases. Copper was demonstrable by the rhodanine method in similar locations but the staining reaction was qualitatively weaker in all cases. Characteristically, there was staining of both parenchymal and mononuclear phagocytic cells. This triad of cirrhosis, strong copper-associated protein deposition and copper positivity was not present in a control group of 20 cases of fulminant hepatic failure of other aetiology and with a similar clinical presentation. It is concluded that in the clinical context of fulminant hepatitis the presence of cirrhosis should raise the suspicion of Wilson's disease and that, with routinely processed and stained tissue, including autopsy tissue, the diagnosis can be made histologically.
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PMID:Hepatic morphology and histochemistry of Wilson's disease presenting as fulminant hepatic failure: a study of 11 cases. 280 95

The ability to induce granulomatous hepatitis has been attributed to numerous drugs; some sixty causative drugs have been culled from the literature for this review. Additionally, granulomas or granulomatoid lesions have resulted from occupational exposure to toxic substances (e.g. silica, copper sulphate, beryllium compounds), and particulate material from various therapeutic or diagnostic procedures (e.g. reactions to starch, talc, suture material, polyvinyl pyrrolidone, silicone, barium sulphate, thorium dioxide) or from intravenous drug abuse (e.g. talc). Clinically, patients with drug-induced or toxic granulomatous hepatitis may be asymptomatic. More frequently, the presentation is that of an acute febrile illness, with or without a rash and eosinophilia, followed by jaundice and biochemical evidence of hepatic dysfunction. The diagnosis of drug-induced granulomatous hepatitis is based largely on ruling out other aetiologies. Liver biopsy plays a key role in diagnosis. Recovery is the rule following withdrawal of the drug. Morphologically, drug-induced granulomas may be impossible to distinguish from those due to other causes. Associated lesions suggesting a drug aetiology include significant tissue eosinophilia, unicellular hepatocytic degeneration and necrosis, cholestasis and acute cholangitis or vasculitis. Special stains, polarizing and phase contrast microscopy, transmission and scanning electron microscopy and energy dispersive X-ray microanalysis all play a role in the aetiologic diagnosis of some types of granulomas.
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PMID:Drug-induced and toxic granulomatous hepatitis. 304 71

Livers of nine related Skye terriers with liver disease were evaluated for histological changes and copper content. Lesions ranged from hepatocellular degeneration and necrosis (zone 3) with intracanalicular cholestasis and mild inflammation, to chronic hepatitis with cholangioplasia and cirrhosis. Excess copper (801-2,257 micrograms/g) was related to the severity of cholestasis. Skye terrier hepatitis is a distinct disease entity and may be derived from a disorder of intracellular bile metabolism culminating in disturbed bile secretion and the accumulation of copper.
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PMID:Hepatitis and copper accumulation in Skye terriers. 321 85

Although copper is believed to be hepatotoxic in Wilson's disease and Indian Childhood Cirrhosis (ICC), the rat shows only minimal hepatic damage on copper-loading. To investigate the possibility that copper deposition may potentiate the effects of a superimposed hepatitis, D-galactosamine (GalN) was given to copper-loaded and control rats. In the non-copper-dosed rats, GalN 0.85 g/kg i.p. produced elevated serum AST (3731 +/- 545 IU/l; normal 64.8 +/- 2.1), ALT (2090 +/- 190 IU/l; normal 18.0 +/- 0.7), and OCT (16.7 +/- 2.6 mmol/min/ml; normal 0.12 +/- 0), and liver cell necrosis with portal infiltration. In rats whose liver copper was elevated to 1298 +/- 169 micrograms/g (control 18.7 +/- 1.7) by oral copper supplementation, GalN produced much smaller increases in AST (825 +/- 122 IU/l), ALT (103 +/- 15 IU/l) and OCT (0.27 +/- 0.02 mmol/min/ml) and minimal histological damage. Viable bacterial cell counts from faecal homogenates showed that the anaerobically cultured bacteria were reduced on copper-dosing of rats. Therefore the protective effect of copper may be due to a decrease in gut-derived endotoxin acting on the liver, or to an impaired prostaglandin synthesis or perhaps to synthesis of acute phase reactants.
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PMID:Copper protects against galactosamine-induced hepatitis. 365 8


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