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

Methoxsalen, a potent suicide inhibitor of cytochrome P-450 that can be used in humans, might be of value for the prevention of hepatitis in subjects with carbon tetrachloride poisoning. As a preliminary step, we have determined its effects on the hepatotoxicity of carbon tetrachloride in mice. Several monooxygenase activities, the in vitro covalent binding of carbon tetrachloride metabolites to microsomal proteins, and in vitro microsomal lipid peroxidation initiated by carbon tetrachloride metabolites were decreased by 60-90% in microsomes from mice killed 2 hr after the administration of methoxsalen (250 mumol X kg-1); microsomal lipid peroxidation mediated by endogenous iron and NADPH was not modified. Administration of methoxsalen (250 mumol X kg-1) 30 min before carbon tetrachloride (0.1 ml X kg-1) decreased both the in vivo formation of conjugated dienes in microsomal lipids and the in vivo covalent binding of carbon tetrachloride metabolites to lipids and proteins. This pretreatment completely prevented the hepatotoxicity of carbon tetrachloride. Other cytochrome P-450 inhibitors (cimetidine, SKF 525-A or piperonyl butoxide) given at this low molar dose (250 mumol X kg-1) exerted no protective effect. Methoxsalen (500 mumol X kg-1) was also effective, but only partially, when given 30 min after carbon tetrachloride (0.025 ml X kg-1). We conclude that pretreatment with methoxsalen decreases the metabolic activation of carbon tetrachloride, and completely prevents its hepatotoxicity in mice. Post-treatment with methoxsalen must be given early and is only partially effective in mice.
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PMID:The drug methoxsalen, a suicide substrate for cytochrome P-450, decreases the metabolic activation, and prevents the hepatotoxicity, of carbon tetrachloride in mice. 310 41

Liver biopsies were performed on 51 regularly transfused patients with beta thalassaemia, age range 5-36 (mean 18.6) years, who had received regular subcutaneous desferrioxamine (DFX) treatment for periods between one and eight years (40 for eight years). The biopsy specimens were examined by light microscopy and immunofluorescence for hepatitis B virus surface and core antigens (HBsAg and HBcAg), and the iron content was determined chemically. The results were compared with serum ferritin concentration and aspartate transaminase (AST) activity and with hepatitis B virus serology. Biopsy specimens, in which chemical liver iron had been determined in 12, were also available from 17 patients. Mean serum ferritin (+/- SD) had fallen from 5885 (3245) micrograms/l to 1638 (976) micrograms/l in 36 patients after eight years' chelation, while mean (+/- SD) liver iron concentration had fallen from 2945 (900) micrograms/100 mg dry weight to 857 (435) micrograms/100 mg dry weight in 12 of them. All biopsy specimens examined were negative for HBs and HBc antigens. The presence of histological features of hepatitis was associated with increased liver iron content, increased fibrosis, and with progression of fibrosis between the two biopsies. Procollagen III peptide was assayed in 28 patients but did not correlate with the degree of hepatitis, fibrosis, or with chemical liver iron content. We conclude that with regular subcutaneous DFX, mean concentrations of serum ferritin and liver iron are maintained in these patients at about five and 10 times the normal value, respectively, and that progression of liver damage is more likely to be due to viral hepatitis, presumably related to the parenterally transmitted non-A, non-B agents than to iron overload.
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PMID:Iron state and hepatic disease in patients with thalassaemia major, treated with long term subcutaneous desferrioxamine. 312 79

Fifty-five patients with suspected parenchymal liver disease were examined radiologically immediately prior to percutaneous liver biopsy. Radiological examination consisted of independently performed ultrasound, X-ray computed tomography, proton magnetic resonance and radionuclide liver studies. It was found that none of these scan techniques, alone or in any combinations, could accurately diagnose or exclude liver disease. Calculated mean hepatic T1 relaxation values (measured in vivo at 3.4 MHz) did not indicate the presence or amount of fatty, inflammatory or cirrhotic change in the liver. A tendency for livers with hepatitis and cirrhosis to have a prolonged mean T1 relaxation value was noted, while the pathological accumulation of excess quantities of intrahepatic iron significantly shortened the mean hepatic T1. In patients with clinically suspected parenchymal liver disease who will undergo percutaneous liver biopsy, we see no justification for the use of proton nuclear magnetic resonance imaging techniques or the in vivo measurement of hepatic T1 relaxation time.
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PMID:Magnetic resonance imaging of parenchymal liver disease: a comparison with ultrasound, radionuclide scintigraphy and X-ray computed tomography. The Clinical NMR Group. 331 63

The quantitative determination of hydrocarbons exhaled by animals as an in vivo index of extensive lipid peroxidation is described. Advantages and limitations of this method are discussed. Acetaminophen-induced hepatic lipid peroxidation in mice is an example of oxidative stress, the extent of which is determined in vivo by the turnover of endoplasmic reticulum monooxygenase and the cofactor, e.g. glutathione status of the liver. In microsomal suspensions, none of the assay methods for lipid peroxidation identifies acetaminophen as a prooxidant. Rather, it acts like an antioxidant. The obvious limitations of in vitro experiments are emphasized. Cytosolic metabolism of allyl alcohol also leads, in a dose-dependent manner, to extensive lipid peroxidation. Evidence is presented that release of iron from intracellular stores following overproduction of NADH may be the primary cause of this lesion. The term reductive stress is suggested for this metabolic initiation of iron redox cycling. In experimental hepatitis induced by galactosamine/endotoxin, a leukotriene-mediated pathomechanism, no signs of lipid peroxidation are detectable. This means that ethane or pentane formation are definitively not late consequences of membrane deterioration but rather early causal events in special cases of hepatotoxicity.
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PMID:Measurement of in vivo lipid peroxidation and toxicological significance. 331 1

We report two sisters with neonatal hemochromatosis (NHC), including the first documented survivor. Characterized by excessive parenchymal iron in liver, pancreas, heart, and other organs, but little iron in the spleen, bone marrow, or other sites of the reticuloendothelial system, NHC is rarely reported and has been uniformly fatal. The first infant (case 1) presented with neonatal hypoglycemia, coagulopathy, and mild hyperbilirubinemia; she rapidly deteriorated and died of multisystem failure. Autopsy showed cirrhosis. Her sister (case 2) presented similarly; liver biopsy showed giant cell hepatitis, which is consistent with idiopathic neonatal hepatitis (INHP). However, iron staining revealed that case 1 had extensive iron deposits in the liver, pancreas, heart, thymus, and bone, but none in bone marrow or spleen. Case 2 had grade 4 liver iron staining, normal bone marrow iron, elevated serum ferritin and transferrin saturation, and HLA-A3 haplotype. At 16 months of age, the growth, development, and serum measures of iron status in case 2 were normal; liver biopsy showed fibrosis, negative iron staining, and normal tissue iron concentration. NHC is compatible with survival, has clinicopathologic features that overlap with INHP, and may frequently be misdiagnosed as INHP. A prospective study is needed to determine the incidence and natural history of NHC--a disorder that may be more common than is currently recognized.
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PMID:Familial neonatal hemochromatosis with survival. 333 84

Liver function has been evaluated in 74 patients (aged 9 months to 19 years) with beta-thalassemia major. They were selected from 212 patients because their transaminase levels were three times higher than normal for over three months. In 36 of these subjects BSF clearance test was performed. In the majority of patients (70%) average GPT serum values were increased (66.33 +/- 35.41 U/L) while only a few of the youngest age group exhibited normal values. The transaminase level showed a direct relationship with age, ferritin level and transfusional iron. Furthermore a direct correlation was found between iron and gamma globulin levels both being related to age. Test for viral hepatitis markers showed that 60% of all the subjects studied had had HBV infection. Twenty-six of the 36 patients who underwent BSF test had normal values in the first part of the clearance curve, 8 others showed moderate changes while only the 2 remaining revealed severe alterations. The second part of the curve was abnormal in 34 and markedly altered in 2 subjects. Mean GPT serum values correlated with the first part of BSF clearance curve and BSF 45' values correlated with transfused iron. Siderosis, fibrosis, chronic inflammatory infiltration and vacuolar degeneration were seen at liver biopsy. Histological findings of chronic aggressive hepatitis were shown in two patients with high transaminase and gammaglobulin levels who had markedly abnormal BSF curve.
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PMID:[Hepatic pathology in beta-thalassemia major]. 372 17

Blood and a variety of tissues from 97 patients with the acquired immunodeficiency syndrome (AIDS) and 25 with the AIDS prodrome were studied ultrastructurally. Tubuloreticular structures (TRS) were found in 85 per cent of the patients with AIDS and in 92 per cent of those with the prodrome. Test tube and ring-shaped forms (TRF), found in 41 per cent of the patients with AIDS and in 8 per cent of those with the prodrome, increased with disease progression. Among the patients with AIDS, as the number of sites examined per case increased, the incidence of TRS and TRF tended to approach 100 per cent, suggesting that they are present in all patients with AIDS. Other changes seen frequently were immunologic capping of blood lymphocytes, intramitochondrial iron in blood reticulocytes and marrow normoblasts, megakaryocytic immaturity and platelet phagocytosis, collections of membranous rings in hepatocytic cytoplasm, suggestive of non-A, non-B hepatitis, and proliferations and engorgement of hepatic Ito cells with lipid. The data suggest that TRS and TRF can be used as diagnostic and prognostic markers.
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PMID:The acquired immunodeficiency syndrome: an ultrastructural study. 387 53

Drug interactions involving macrolides have been mainly reported in subjects receiving troleandomycin and in a few receiving erythromycin derivatives. In rats and in humans, troleandomycin, erythromycin and erythromycin derivatives induce microsomal enzymes; the induced isozymes of cytochrome P-450 have a high activity for these macrolides but a poor activity with several other substrates. These isozymes actively demethylate and oxidize these macrolides into nitrosoalkanes which form stable, inactive complexes with the iron of cytochrome P-450. Eventually, the oxidative metabolism of other drugs may be decreased. These effects are marked after administration of troleandomycin, moderate after administration of erythromycin derivatives and absent (or negligible) after administration of spiramycin, josamycin or midecamycin. A second adverse effect of the administration of troleandomycin or erythromycin derivatives is the possible occurrence of hepatitis. Mild hepatic dysfunction is fairly frequent and may be toxic in type. In contrast, jaundice is common, is frequently associated with hypersensitivity, and promptly recurs when the drug is readministered. Troleandomycin and erythromycin derivatives, which form nitrosoalkanes, produce hepatitis, whereas josamycin, midecamycin and spiramycin, which do not form cytochrome P-450-nitrosoalkane complexes, rarely, if ever, produce hepatitis. Nitrosoalkanes are unstable intermediates which react with glutathione but also with cysteine and might covalently bind to the SH-groups of proteins. The following mechanism might be proposed as a hypothetical attempt to link up these various observations. The macrolide (or its reactive metabolite) may have discrete toxicity; in several subjects, this may produce minor liver lesions and a mildly raised aminotransferase activity. Necrosis of a few hepatocytes may release into the circulation plasma membrane proteins altered by the covalent binding of metabolites. Such modified liver antigens may be recognized as foreign and may trigger, in an exceptional subject, an immunoallergic type of clinical hepatitis.
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PMID:Drug interactions and hepatitis produced by some macrolide antibiotics. 387 43

Most pathologic studies of liver disease in sickle cell anemia and its variants were performed retrospectively on autopsy specimens, and, because of the prominent histologic features of intrasinusoidal sickling and Kupffer cell erythrophagocytosis, hepatic dysfunction was attributed to the intrahepatic sickling of erythrocytes in this hemoglobinopathy. We compared the liver histology from 19 patients who had liver biopsies to the autopsy specimens from 32 patients who succumbed to the complications of the hemoglobinopathy. In the former, nine patients had histological evidence of viral hepatitis. Four of these patients had both serological and immunohistochemical evidence of hepatitis B surface antigen. The features of biliary tree obstruction were found in two cases and alcoholic cirrhosis and sarcoid granuloma in one case each. Only one patient, who had recovered from septic shock, showed ischemic necrosis. In five patients incidentally biopsied during cholecystectomy, no significant lesions were found. Fourteen of the autopsy specimens showed ischemic necrosis, a result which was significantly different from the biopsy group. Ten cases had no significant morphologic changes other than heavy iron deposits. There were two cases with chronic active hepatitis, two with diffuse fibrosis, and one case each of cirrhosis, acute viral hepatitis, cholestasis, and giant cell hepatitis. Intrahepatic sickling and erythrophagocytosis were seen in almost all specimens and did not correlate with liver disease or transaminase elevation. Other than the patient with septic shock, ischemic necrosis was found only in postmortem material. These histological features may represent red cell destruction rather than the etiology of liver disease in these patients.
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PMID:Pathological spectrum of liver diseases in sickle cell disease. 394 29

Experimental animal models of hepatitis, fatty liver, and hepatic iron overload were evaluated using a 3.5-kGauss nuclear magnetic resonance (NMR) imaging system. Increases in image intensity measurements and in T2 relaxation times equalled the sensitivity of histologic findings for the detection of early stages of hepatitis. A significant shift in T1 relaxation times characterized the early stages of hepatic necrosis. Liver triglyceride content correlated significantly with increases in NMR intensity measurements (p less than 0.01); however, changes in liver water content had a much greater influence on intensity, T1, and T2. Thus, it may be possible to distinguish hepatitis from benign fatty liver. Liver iron content correlated with decreases in NMR intensity measurements (p less than 0.001), and iron levels as low as 1.2 mg/g were detected. NMR may more specifically identify hepatocellular iron overload than do other techniques that do not distinguish hepatocellular from reticuloendothelial iron.
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PMID:Nuclear magnetic resonance imaging of experimentally induced liver disease. 619 64


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