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)

The hydroxylamine and nitroso metabolites formed by N4-oxidation of sulfonamides are thought to be involved in the pathogenesis of idiosyncratic reactions to this class of drugs. Idiosyncratic reactions to sulfonamides are characterized by multisystemic toxicity, including hepatitis, nephritis, dermatitis, and blood dyscrasias (aplastic anemia, agranulocytosis). We have previously shown that cytochrome P-450 in the liver metabolizes sulfamethoxazole to its hydroxylamine metabolite. In this paper we report the N4-oxidation of sulfamethoxazole by activated monocytes and neutrophils (human and canine) to form sulfamethoxazole hydroxylamine and nitrosulfamethoxazole. The presumed nitroso intermediate was not detected. Purified myeloperoxidase and prostaglandin H synthase were also capable of mediating the oxidation of sulfamethoxazole. The present studies suggest that myeloperoxidase is responsible for the observed oxidation by phagocytic cells. Oxidation by neutrophils may play a role in agranulocytosis, and oxidation by monocytes may facilitate antigen presentation. Extrahepatic bioactivation of sulfonamides by peroxidases in phagocytic cells and other tissues may be important in determining the range of adverse reactions to sulfonamides that occur.
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PMID:Peroxidase-dependent oxidation of sulfonamides by monocytes and neutrophils from humans and dogs. 217 79

In 34 patients with non-A non-B, 28 with type B and 11 with autoimmune chronic hepatitis, anti-neutrophil antibodies were investigated using indirect immunofluorescence and anti-myeloperoxidase antibodies by enzyme-linked immunosorbent assay. Granulocyte-specific antinuclear antibodies, were detected in 14 patients with advanced stages of non-A, non-B hepatitis (41%). Their presence correlated with histological features of disease activity but not with response to interferon therapy. Within 24 h after the first dose of interferon, 9 of these became negative and 3 more became negative after 1, 3 and 5 months. Myeloperoxidase-positive perinuclear neutrophil cytoplasmic antibodies were detected in a single patient and increased reaching a peak level after 8 weeks of interferon, decreasing thereafter. In type B, all were negative before and during the 6 months of therapy. In 6 patients with autoimmune hepatitis (55%), myeloperoxidase-negative perinuclear neutrophil cytoplasmic antibodies were detected in high titers. The association of granulocyte-specific anti-nuclear antibodies with non-A, non-B hepatitis support the hypothesis that hepatitis C virus infection might trigger humoral autoimmune response. In chronic autoimmune hepatitis, perinuclear neutrophil cytoplasmic antibodies appear as another marker of autoimmunity.
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PMID:Anti-neutrophil antibodies in chronic hepatitis and the effect of alpha-interferon therapy. 839 Oct 39

Here we report an autopsy case with anti-neutrophil antibodies (ANCA) associated vasculitis accompanied by autoimmune hepatitis and hepatocellular carcinoma. A 69-year-old woman was admitted to Tokyo Metropolitan Ohtsuka Hospital in October 1995 because of leg edema. She had presented cough in 1990 and diagnosed as interstitial pneumonia, esophageal varices and liver chirosis. On admission, laboratory data showed mild anemia, hypoproteinemia, and marked gammagloblinemia. IgM-HA antibody, HBs antigen, HBs antibody, HCV antibody and HDV antibody were negative. Anti-nuclear antibody, anticentromere antibody, anti-neutrophil cytoplasmic antibody against myeloperoxidase and cathepsin G (MPO-ANCA and cathepsin G), rheumatoid factor and direct coombs test were positive. Serum level of AFP and CEA were elevated. Ultrasonography and computed tomography of abdomen scowed liver chirosis and tumor in left lobe of liver. The diagnosis of liver chirosis based on autoimmune hepatitis and Interstitial pneumonia was made with clinical course, laboratory findings and radiographic findings although liver biopsy was not performed. She complained of bloody stool due to ulcer of the large intestine, and died of liver failure which progressed rapidly. The autopsy findings detected that pulmonary fibrosis, liver fibrosis with multiple hepatocellular carcinoma, necrotizing crescentic glomerulonephritis, and vasculitis of small artery inn colon. This was the first report of MPO-ANCA associated vasuculitis complicated with autoimmune hepatitis and hepatocellular carcinoma. Clinical significance of ANCA and immunogenetic background of these diseases were discussed.
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PMID:[An autopsy case of anti-neutrophil cytoplasmic antibodies associated vasculitis accompanied by autoimmune hepatitis and hepatocellular carcinoma]. 917 69

We studied a case of a 63 year old Japanese man who presented in October, 1994 with general fatigue, low grade fever, micro hematuria and leukocytosis, elevated CRP as well as liver dysfunction. A liver biopsy at that time revealed mild cholangiolitis. Six months later he was admitted because of weight loss, protein urea, and renal failure. At that time he was positive for antineutrophil cytoplasmic antibody(ANCA) with perinuclear staining patter(p-ANCA) done by indirect immunofluorescence. He was also positive for anti-myeloperoxidase antibody(MPO-ANCA) done by ELISA. A renal biopsy showed idiopathic crescentic glomerulonephritis with pauci-immune type(ICGN). Despite therapy with steroids and cyclophosphamide, which improved his subjective symptoms, his renal failure accelerated necessitating hemodialysis which he has been on for over four years. In conclusion, this patient has a rare case of ICGN that presented with liver dysfunction similar to autoimmune hepatitis. Since ANCA has been known to be associated with systemic vasculitides as well as chronic inflammatory diseases(e.g. ICGN, microscopic polyarteritis nodosa, ulcerative colitis or autoimmune liver diseases), both the crescent formation in this patient's glomeruli and cholangiolitis in his liver may have shared the common etiology related to ANCA.
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PMID:[A case of ANCA positive idiopathic crescentic glomerulonephritis initiated with fever and liver dysfunction]. 1089 76

The functional metabolic activity of peripheral blood neutrophils in acute virus hepatitis B (VHB) and/or virus hepatitis C (VHC) was evaluated. 48 patients were examined; of these, VHB was diagnosed in 28 patients and VHC was diagnosed in 9 patients and the mixed form of virus hepatitis (VHB + VHC), in 11 patients. Determination of adhesive capacity of neutrophils, production of superoxidase anion in the nitro blue tetrazolium (NBT) test, activity of myeloperoxidase (MPO) and acidic phosphatase (AP), the amount of cation proteins (CP) was made. Most pronounced functional dysbalance of neutrophil leukocytes and considerable changes in biochemical characteristics of the activity of the infectious process in patients with the mixed form of virus hepatitis were established. These data demonstrated that in acute virus hepatitis B and C at the peak of the disease such characteristics of the functional activity of neutrophils as results of the NBT test, the activity of MPO and AP, as well as the amount of CP, were highly informative.
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PMID:[Functional and metabolic activity of peripheral blood neutrophils in acute viral hepatitis B and C]. 1123 2

The effect of perftoran on the course of experimental acute hepatitis in albino rats was studied on the hepatitis models induced by allyl alcohol or P. acnes culture with typhoid fever endotoxin. Perftoran (10 ml/kg) favored more rapid cytolytic syndrome elimination by affecting the lipid peroxidation in rat liver. The drug inhibits the activity of prooxidant enzymes (xanthine oxidase and myeloperoxidase of Kupffer cells) and induces the synthesis of factors accounting for the antiperoxidation protection in hepatocytes such as catalase, glucose-6-phosphate dehydrogenase, and reduced glutathione.
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PMID:[Effect of perftoran on experimental hepatitis]. 1156 5

Ozone is one of the most powerful oxidants available, with many applications in industry and medicine. Medically relevant features of ozone include bacterial and virucidal properties, disinfection, sterilization, circulatory stimulation, and disruption of malignant cells. Ozone therapy is administered in various ways, including intravenously, intramuscularly, and intrarectally. The latter modality is used for the treatment of colitis and hepatitis. Our aim was to examine the effect of ozone water enema on normal and inflamed rat colonic mucosa. Ozone water (20 microg/ml) was prepared via ozone generator and administered intrarectally (0.5 ml) daily. Rats were killed one, three, and seven days after rectal ozone water administration, and their colons resected, rinsed, and weighed (grams per 10 cm). Damage was assessed macro- and microscopically and tissue processed for myeloperoxidase and nitric oxide synthase activity. Rats receiving saline served as controls. In an additional experiment colitis was induced by intrarectal iodoacetamide. Ozone therapy caused no macroscopic damage. Ozone therapy induced microscopic colitis, which lasted for at least a week and was accompanied by increase in segmental weight, myeloperoxidase and nitric oxide activity, and prostaglandin E2 generation. Ozone therapy had no protective effect on inflamed mucosa. In conclusion, ozone water therapy had a deleterious effect on normal colonic mucosa, suggesting intrarectal administration be reevaluated. Ozone water enema may serve as a model of microscopic colitis.
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PMID:Ozone enema: a model of microscopic colitis in rats. 1171 63

Previous studies have suggested that increased nitric oxide (NO)-mediated products are found in the livers of subjects with primary biliary cirrhosis (PBC), but the mechanisms involved remain enigmatic. We took advantage of immunohistochemistry and several unique monoclonal antibodies to study inflammatory cells responsible for the generation of NO, the enzymes responsible for NO production, the expression of 3-nitrotyrosine, and the presence of CD68(+) and/or myeloperoxidase (MPO)(+) cells. We examined a total of 113 liver specimens, including 64 with PBC, 19 with primary sclerosing cholangitis (PSC), 6 with non-A, non-B hepatitis, 6 with alcoholic liver disease, 4 with cryptogenic cirrhosis, 4 with biliary atresia, and 10 normal subjects. Twenty-two percent of PBC had elevated expression of 3-nitrotyrosine in their bile duct epithelial cells (BECs) (P =.0316). Furthermore, the BECs in PBC also demonstrated apoptotic changes. MPO-positive inflammatory cells were also noted adjacent to the basement membrane. In contrast, the liver of normal subjects showed few apoptotic changes in the bile ducts, with no evidence of MPO staining in the portal area. Furthermore, sections from livers of subjects with stage I or stage II PBC demonstrated significantly increased inflammatory cell infiltration (P =.0064) and elevated 3-nitrotyrosine expression in BECs (P =.0246) compared with stage III and IV. The presence of 3-nitrotyrosine was closely associated with infiltrating CD68- and/or MPO-positive cells. There was also a stage-associated difference in the presence of bile duct infiltrating cells and 3-nitrotyrosine in PBC with an increase dominant in early stage disease. In conclusion, NO and reactive oxygen species, collectively determined as 3-nitrotyrosine, are associated with bile duct destruction in PBC and are particularly prevalent in early stage disease.
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PMID:Myeloperoxidase-positive inflammatory cells participate in bile duct damage in primary biliary cirrhosis through nitric oxide-mediated reactions. 1451 89

A 17-year-old woman was admitted because of proteinuria, microhematuria and liver dysfunction with increased antinuclear antibody and anti-myeloperoxidase antibody (MPO-ANCA). Fourteen months' previously, urinalysis and liver function showed normal range. At that time she suffered from tachycardia and weight reduction, diagnosed as Graves' disease, she was given propylthiouracil for treatment of her Graves' disease. The histological finding of renal biopsy was compatible with minor glomerular abnormalities. Liver biopsy finding was compatible with autoimmune hepatitis. After we had administered prednisolone, liver function returned to normal range and urine protein became negative. Then we performed subtotal thyroidectomy, and she was not given propylthiouracil. MPO-ANCA decreased gradually.
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PMID:Graves' disease accompanied by anti-myeloperoxidase antibody-related nephropathy and autoimmune hepatitis. 1528 91

Long-term treatment of hypertensive disorders with hydralazine has resulted in some patients developing hepatitis and lupus erythematosus, an autoimmune syndrome. The concentration of hydralazine required to cause 50% cytotoxicity in 2 h (LC(50)) toward isolated rat hepatocytes was found to be 8 mM. Cytotoxicity was delayed by the P450 inhibitor, 1-aminobenzotriazole, suggesting that P450 catalyzed the formation of toxic metabolites from hydralazine. No hydralazine-induced oxidative stress was apparent as there was little effect on hepatocyte lipid peroxidation, protein carbonyl formation, intracellular H(2)O(2), or hepatocyte GSH levels and no effect of butylated hydroxyanisole (BHA) on cytotoxicity. Drug-induced hepatotoxicity in vivo has often been attributed to infiltrating inflammatory cells, for example, neutrophils or resident Kupffer cells whose NADPH oxidase generates H(2)O(2), when activated. The effect of a nontoxic continuous infusion of H(2)O(2) on hydralazine cytotoxicity was investigated. It was found that H(2)O(2) increased hepatocyte susceptibility to hydralazine 4-fold (LC(50), 2 mM). Cytotoxicity was still prevented by the P450 inhibitor but now involved some oxidative stress as shown by increased protein carbonyls, endogenous H(2)O(2), and GSH oxidation. Lipid peroxidation was not increased, and cytotoxicity was not inhibited by BHA. Cytotoxicity, however, was inhibited by 4-hydroxy-2,2,6,6-tetramethylpiperidene-1-oxyl (TEMPOL), a ROS scavenger. Because neutrophils or Kupffer cells release myeloperoxidase on activation, the effect of adding peroxidase to the hepatocytes exposed to H(2)O(2) on hydralazine cytotoxicity was investigated. It was found that peroxidase/H(2)O(2) increased hepatocyte susceptibility to hydralazine 80-fold (LC 50, 0.1 mM). Furthermore, cytotoxicity occurred following extensive oxidative stress that included lipid peroxidation, and cytotoxicity that was now prevented by the antioxidant BHA. These results indicate that three cytotoxic pathways exist for hydralazine: a P450-catalyzed pathway not involving oxidative stress, a P450/H(2)O(2)-catalyzed oxidative stress-mediated cytotoxic pathway not involving lipid peroxidation, and a peroxidase/H(2)O(2)-catalyzed lipid peroxidation-mediated cytotoxic pathway.
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PMID:Accelerated cytotoxic mechanism screening of hydralazine using an in vitro hepatocyte inflammatory cell peroxidase model. 1839 51


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