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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trace elements were examined spectrophotometrically in 45 patients with chronic hepatitis (persisting--31; chronic--14). Lead and cadmium showed a significant increase both in the healthy and hepatitis patients. A reduction of zinc and increase of copper was found in patients with chronic hepatitis. Changes in the content of microelements depended on the severity of the disease.
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PMID:[Changes in the trace element content of the blood in chronic hepatitis]. 148 45

Zinc acetate was used for the treatment and prophylaxis of hepatic copper toxicosis in 3 Bedlington Terriers and 3 West Highland White Terriers. Two dogs of each breed were treated for 2 years, and 1 of each breed for 1 year. A dosage of 200 mg of elemental zinc per day was required to achieve therapeutic objectives related to copper, which included a doubling of plasma zinc concentration to 200 micrograms/dl and a suppression of oral 64 copper absorption. The dosage was later reduced to 50 to 100 mg/day to avoid an excessive increase in plasma zinc concentration. The preliminary clinical results were good. Three dogs had mild to moderate active liver disease and high liver copper concentrations at the time of initiation of zinc administration. Biopsy of the liver 2 years later revealed a reduction in hepatitis and copper concentrations. One other dog without active hepatitis also had a reduction in hepatic copper concentrations over a 2-year period. All 6 dogs have done well clinically. On the basis of these findings, we believe zinc acetate to be an effective and nontoxic treatment for copper toxicosis in dogs.
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PMID:Use of zinc acetate to treat copper toxicosis in dogs. 151 30

The copper concentrations in organs of developing Long-Evans Cinnamon (LEC) rats (2 d to 13 mo) were measured to elucidate the pathogenesis of their hereditary hepatitis. Hepatic copper contents of LEC rats were significantly higher than those of control rats (26 to 92 times higher). The subcellular distribution of hepatic copper indicated that the nuclear and large granular fractions had been saturated and the cytosol fraction contained about 70% of all the hepatic copper in LEC rats. The serum concentrations of copper and ceruloplasmin were significantly lower than those of control rats from the 4th wk (10-12% and 5-19%, respectively). Copper contents in kidney of LEC rats did not exhibit an increase over those of control rats until 12 wk, but then increased to nearly 40 times higher during fulminant hepatic failure. Accumulation of copper was not detected in the brain or small intestines of LEC rats until 13 mo. The hepatic copper concentration, its subcellular distribution, and serum copper concentration of F1 rats (LEC x Long-Evans Agouti) exhibited the same levels as those of Long-Evans Agouti rats. In addition to their similarity concerning inheritance of autosomal recessive means and clinical course, we found causality relating copper accumulation to the pathogenesis of the disease. We propose that LEC rats will be the most promising animal model for the study of Wilson's disease.
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PMID:Inherited copper toxicity in Long-Evans cinnamon rats exhibiting spontaneous hepatitis: a model of Wilson's disease. 156 Oct 10

The disposition behaviors and de-coppering effect of triethylenetetramine dihydrochloride (trientine), a selective chelating agent for copper and an 'orphan drug' for Wilson's disease, have been evaluated in an animal model, Long-Evans Cinnamon (LEC) rats, and normal rats (Wistar). In LEC rats, urinary excretion of trientine was remarkably lower than that of Wistar rats. The absorption rates from the jejunal loop and in vitro metabolism in the liver S9 fraction (supernatant of 9000 x g) were approximately the same for both strains. The decline of urinary excretion of trientine in LEC rats is thought to be due mainly to the lowering of the functional activity of the kidney, because urinary excretion of creatinine and phenolsulfonphthalein were significantly lower in LEC rats than those in Wistar rats. Both acceleration of urinary excretion of copper and reduction of hepatic copper levels were observed with treatment of trientine in LEC rats aged 6 weeks. In LEC rats aged 13 weeks, however, no de-coppering effect from the liver was observed, though urinary excretion of copper was increased. These results suggest that trientine has a pharmacological effect in disease state, especially in the early stages of hepatitis.
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PMID:Comparison of disposition behavior and de-coppering effect of triethylenetetramine in animal model for Wilson's disease (Long-Evans Cinnamon rat) with normal Wistar rat. 160 Jan 13

Recently, copper (Cu) was found to be unusually accumulated, suggesting the induction of metallothionein (MT) in the liver of LEC rats (Long-Evans rats with a cinnamon-like coat color), which develop spontaneous jaundice with hereditary hepatitis. Thus, the direct relationship between the unusual Cu accumulation and the induction of Cu-MT was investigated by giving LEC rats Cu-overloaded or Cu-deficient diets. Results based on the determinations of Cu and MT levels in several organs, as well as the gel-filtration profiles of the cytosols of liver homogenates, showed that dietary Cu induced Cu-MT and development of hepatic injury associated with jaundice.
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PMID:Copper-metallothionein induction in the liver of LEC rats. 161 Mar 50

Wilson's disease is named after Kinnier Wilson (1878-1937), a famous British neurologist. It is an inherited condition, due to an excess of copper in the liver and brain. The mechanism is unknown, but the gene has been mapped to chromosome 13. The worldwide prevalence is about 30 per million. Patients present with liver disease and/or neuropsychiatric manifestations. Early diagnosis is crucial because there is an effective treatment. This treatment, usually with penicillamine, must be continued for life and without interruption. Liver transplantation may be lifesaving in patients with fulminant hepatitis, or with severe liver disease which is unresponsive to treatment.
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PMID:Wilson's disease, Kayser and Fleischer's sign and Walshe's treatment. 179 99

A new mutant developing spontaneous hepatitis and hepatocellular carcinoma has been discovered among Long Evans rats. Hepatitis appears suddenly in the mutant, Long Evans Cinnamon (LEC) rats, three to four months after birth. Characteristic clinical signs of the hepatitis are jaundice, bilirubinuria, subcutaneous bleeding and loss of body weight. The affected rats showed a high mortality and histological changes with focal necrosis of hepatocytes and infiltration of a few inflammatory cells. Genetic studies indicate that a single autosomal recessive gene is responsible for the hepatitis. Long-surviving rats show chronic hepatitis, and subsequently develop hepatocellular carcinoma at one and a half years of age. We recently found an abnormal copper accumulation in the liver of LEC rats prior to development of the hepatitis. Copper concentration in the liver is over 40 times more than that of normal Long Evans Agouti (LEA) rats, whereas the serum ceruloplasmin and copper levels are lower. An excess of toxic-form copper, free copper, will cause DNA damage in the presence of free radicals and oxygen radicals. Such DNA damage by the radicals is considered to be responsible for hepatic necrosis and hepatocellular carcinoma in LEC rats.
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PMID:Hepatocarcinogenesis in the LEC rat with hereditary hepatitis. 184 50

Both young (5 weeks old) and old (61-100 weeks old) hereditary hepatitis LEC rats showed a markedly low level of plasma ceruloplasmin (Cp) ferroxidase activity as compared with that of age-matched LEA and BN strain rats. This trait was genetically examined by the use of (BN x LEC) F1 hybrid and (F1 x LEC) backcross rats. The F1 hybrids never developed hepatitis and showed a similar level of Cp to that found in the parental BN rats. Among the backcross rats with about 1:1 segregation rate for hepatitis, affected rats had a remarkably decreased level of Cp, as found in LEC rats, whereas unaffected rats exhibited a similar level of Cp to that of BN, F1 and LEA rats. These results indicate that the low level of Cp is heritable in a single autosomal recessive mode in LEC rats. The observed tight link between the low Cp level and the hepatitis in LEC rats suggests that defective copper metabolism may be associated with the occurrence of hepatitis in LEC rats, since Cp is a copper-binding protein primarily involved in copper transport from the liver.
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PMID:Hereditary low level of plasma ceruloplasmin in LEC rats associated with spontaneous development of hepatitis and liver cancer. 190 93

We studied the copper concentrations in the non-cancerous and cancerous liver tissues of LEC rats with hereditary hepatitis and spontaneous hepatoma by atomic absorption spectrophotometry. Copper concentration in the non-cancerous livers of 29-month-old male LEC rats was comparable to that in the livers of LEC rats aged 2, 3 and 8 months whose hepatic copper concentrations were more than 40 times those of normal LEA rats. Copper concentration in spontaneously developed hepatocellular carcinomas of the 29-month-old male LEC rats was lower than that in the surrounding non-cancerous liver tissues, but was still more than 39 times that of 8-month-old male LEA rats. These findings suggest that in LEC rats an abnormal copper metabolism may be maintained during the process of hepatic carcinogenesis.
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PMID:Abnormal copper accumulation in non-cancerous and cancerous liver tissues of LEC rats developing hereditary hepatitis and spontaneous hepatoma. 190 94

The LEC rat is a mutant inbred strain isolated from Long-Evans rats, which spontaneously develops hepatitis and hepatoma with high frequency. In this study, copper profiles of LEC rats, including copper concentration in the liver and concentrations of copper and ceruloplasmin in the serum, were investigated. It was found that copper accumulated in the liver of LEC rats immediately prior to the onset of hepatitis with a concentration of more than 50 times that of normal LEA rats, and serum concentrations of copper and ceruloplasmin decreased markedly, which resembled biochemically characteristic features of human Wilson's disease. Administration of d-penicillamine (100 mg/Kg/day p. o), a chelating agent, reduced the hepatic copper level and completely inhibited the development of hepatitis in LEC rats. Copper also accumulated in both cancerous and non-cancerous liver tissues of three 29-month old male LEC rats which had spontaneously developed hepatocellular carcinomas. These findings suggest that the hepatitis in LEC rats is caused by copper toxicity, and that the abnormal copper metabolism may be involved in hepatic carcinogenesis in the LEC rats. Therefore, it is considered that the LEC rat will provide a promising animal model for not only elucidating the pathogenesis of Wilson's disease and developing treatment strategies of the disease, but also for studying the role of copper in hepatic carcinogenesis.
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PMID:[Abnormal hepatic copper accumulation and its significance in LEC rats developing spontaneous hepatitis and hepatoma]. 195 41


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