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)

A 25 year-old woman diagnosed as acute myelocytic leukemia (M0) suffered a fourth relapse in February 1992 at which time she already had anthracycline-induced cardiac dysfunction. Although remission was induced by low dose cytosine arabinoside and etoposide combined with pirarubicin, she developed acute heart failure followed by extreme elevation of transaminases level and DIC. Abdominal echography and CT revealed small round lesions in the liver. We diagnosed this episode as ischemic hepatitis because of the following clinical findings; serological markers of virus hepatitis were negative, hypotension and reduced blood flow to the liver were seen, and both transaminases and LDH were markedly elevated. Dobutamin and oxygen inhalation were started, her liver function returned to almost normal levels 8 days later.
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PMID:[Ischemic hepatitis due to anthracycline-induced cardiac insufficiency in a patient with acute myelocytic leukemia (M0)]. 771 77

We examined the interactive effect of several cytokines (interleukin-1 beta [IL-1 beta], tumor necrosis factor alpha [TNF-alpha], interferon gamma [IFN-gamma], IL-6, IFN-alpha/beta, and hepatocyte growth factor [HGF]) presumably involved in hepatitis, on primary cultured murine hepatocytes. Among these cytokines, only IFN-gamma induced LDH release from hepatocytes in both time- and dose-dependent fashions. The cytotoxic effect was inhibited by antiserum-containing anti-mouse IFN-gamma monoclonal antibodies (R4-6A2). Moreover, intriguingly, IFN-gamma induced DNA fragmentation in the hepatocytes in a time- and dose-dependent fashion according to the gel electrophoresis of genomic DNA and flow cytometry analysis. These results suggest that the cytotoxic effect of IFN-gamma on hepatocytes was caused by inductive apoptosis. The LDH release and DNA fragmentation induced by IFN-gamma were inhibited by HGF in a dose-dependent manner, whereas they seemed to be accelerated by TNF-alpha. Flow cytometry analysis of the nuclei of treated hepatocytes confirmed the interactions in DNA degradation. The DNA synthesis of cultured hepatocytes was also reduced by IFN-gamma but recovered by hepatocyte growth factor. Taken together, IFN-gamma is presumed to be a critical cytokine in hepatic damage, and the network composed of IFN-gamma, TNF-alpha, and HGF may play an important role in the regulation of liver injury.
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PMID:Protective effect of hepatocyte growth factor on interferon-gamma-induced cytotoxicity in mouse hepatocytes. 776 3

The effects of PGE1.CD on dimethylnitrosamine (DMN)-induced acute liver damage with intravascular coagulation in rats were biochemically and histopathologically investigated. PGE1.CD was administered i.v. from 30 min before to 24 hr after DMN-intoxication (pretreatment) and from 30 min after or from 4 hr after to 24 hr after DMN-intoxication (post-treatment). Pretreatment with PGE1.CD (0.2-2 micrograms/kg/min) dose-dependently suppressed the decrease of platelet counts and the elevation of blood biochemical parameters (PT, HPT, GOT, GPT, LDH, LAP, T-Bil) caused by DMN-intoxication. PGE1.CD (0.5 microgram/kg/min and over) significantly suppressed the DMN-induced histopathological changes (occurrence of hemorrhage and necrosis). Post-treatment with PGE1.CD (2 micrograms/kg/min) also suppressed the liver damage. Furthermore, pretreatment with PGE1.CD (2 micrograms/kg/min) not only suppressed the disruption of hepatocytes, but also prevented the damages of sinusoidal endothelial cells and lysosomal membrane, and it reduced the increase of lipid peroxidation. PGE1.CD (1 microgram/kg/min and over) significantly suppressed the decrease of hepatic tissue blood flow caused by DMN-intoxication. These results demonstrate that PGE1.CD has therapeutically efficacy against DMN-induced acute liver damage in rats; Therefore, it will be clinically useful for the treatment of severe hepatitis such as fulminant hepatitis with intravascular coagulation in the sinusoid.
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PMID:[Inhibitory effects of prostaglandin E1.alpha-cyclodextrin (PGE1.CD) on dimethylnitrosamine-induced acute liver damage in rats]. 777 59

Following a three-week administration of alpha-interferon (IFN-alpha), a 62-year-old woman with chronic hepatitis C manifested fever and dyspnea and showed diffuse infiltrative opacities on chest roentgenograms. Her laboratory data included results of anemia with reticulocytosis, a decreased complement level and hepatitis with elevated ALP, LDH and gamma-GTP. Because laboratory data also revealed a positive lymphocyte stimulation test for IFN-alpha, this cytokine was considered to be responsible for the development of interstitial pneumonia, hemolytic anemia and cholestatic liver dysfunction due to its immunomodulatory effects. Although these three disorders have been reported to develop singly after IFN-alpha therapy, this is the first report of a patient in whom these disorders occurred simultaneously.
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PMID:A patient with chronic hepatitis C who simultaneously developed interstitial pneumonia, hemolytic anemia and cholestatic liver dysfunction after alpha-interferon administration. 791 19

Rubella was accompanied by hepatic dysfunction in a 28-year-old male. Serum aminotransferase levels were moderately elevated and LDH markedly increased, especially LDH isoenzyme 5, whereas total bilirubin and ALP remained almost normal. GOT, GPT and LDH levels were completely normalized by the 21st hospital day. Paired antibody titers of viruses which may cause hepatitis, other than rubella, were of no significance. Laparoscopy showed enlarged, red liver. Histologic and electron microscopic findings of the liver were consistent with acute hepatitis. Hepatic damage with rubella is rare, and it is possible that the hepatic dysfunction seen in adult rubella may be mediated by an immunopathologic mechanism.
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PMID:Hepatitis in an adult with rubella. 828 39

We report a case of suspected liver dysfunction after general anesthesia with sevoflurane. A 30 day old male infant underwent inguinal herniorrhaphy under sevoflurane anesthesia (sevoflurane concentration: 1.3-1.5% with 50% oxygen and nitrous oxide). Two days after the operation, he developed frequent vomiting, anorexia and fever. GOT, GPT and LDH values were 242 Ku, 326 Ku and 901 Wu, respectively and peaked at 520 Ku, 709 Ku and 1000 Wu 12-16 days after the operation. Clinical symptoms and the laboratory data became normal within 2 months. The antibody titers of EB-virus, cytomegalo-virus and HA-virus were all within normal ranges and HBs antigen was negative. There were no blood transfusion or antibiotics administration before the onset, and no epidemic of hepatitis around him. His mother had no history of hepatitis during her pregnancy. Lymphocyte stimulation test for indication of sevoflurane allergy was also negative. From these evidences, toxic (not allergic) liver dysfunction due to exposure to sevoflurane was considered to be the most probable diagnosis.
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PMID:[A case of suspected liver dysfunction induced by sevoflurane anesthesia]. 832 Aug 10

In a few patients diclofenac produces mild increases in serum aminotransferase activity and in rare cases may be associated with the occurrence of fulminant hepatic necrosis. Both direct toxic effects of a diclofenac metabolite and hypersensitivity reactions have been suggested as possible molecular mechanisms of liver injury. We investigated the pathways of bioactivation and cytotoxicity of diclofenac, which undergoes both aromatic hydroxylation and acyl glucuronidation, in short-term cultured rat hepatocytes. LDH release was first evident after 4 hr of incubation with diclofenac (> 500 microM). In addition, time- and concentration-dependent covalent binding of [14C]diclofenac to hepatocellular proteins occurred, indicating the presence of a reactive intermediate. To specifically explore the role of the acyl glucuronidation pathway in the induction of cytotoxicity and covalent drug-protein adducts, we used two inhibitors of the UDP-glucuronosyltransferase (UDPGT), borneol and 7,7,7-triphenylheptyl-UDP. LDH release was markedly increased in the presence of either UDPGT inhibitor. Alternatively, covalent binding to hepatocellular proteins was greatly reduced when the glucuronide formation was selectively blocked. Furthermore, in vitro inhibition of P450-dependent oxidative biotransformation with the selective inhibitor of the CYP2C subfamily sulfaphenazole or with cimetidine markedly reduced the extent of cytotoxicity, whereas the degree of covalent adduct formation remained unchanged. Similarly, pretreatment of the rats with phenobarbital (80 mg/kg/day for 4 days) delayed the onset and reduced the extent of diclofenac-induced LDH release. Collectively, these results indicate that the formation of a toxic diclofenac metabolite(s) catalyzed by P4502C in hepatocytes leads to acute lethal cell injury, whereas diclofenac acyl glucuronide formation is associated with covalent binding of a reactive metabolite to hepatocellular proteins that is not related to the acute cytotoxicity. The protein adduct formation and its modulation by UDPGT may, however, be toxicologically relevant for the expression of diclofenac hepatitis.
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PMID:Diclofenac covalent protein binding is dependent on acyl glucuronide formation and is inversely related to P450-mediated acute cell injury in cultured rat hepatocytes. 851 77

Hepatoprotective effect of celosian, an acidic polysaccharide isolated from the water extract of the seed of Celosia argentea, was investigated using chemical and immunological liver injury models. Celosian inhibited the elevation of serum enzyme (GPT, GOT, LDH) and bilirubin levels on carbon tetrachloride (CC1(4))-induced liver injuries in rat. In addition, the hepatoprotective effect of celosian was also observed in this model of liver injury by histopathological findings. Moreover, celosian suppressed rises in GPT or mortality on fulminant hepatitis induced by D-galactosamine/lipopolysaccharide (D-Ga1N/LPS) or Propionibacterium acnes/LPS in mice. These findings suggested that celosian is an active component in protection against chemical and immunological hepatitis and the activity was found to be a dose dependent. Celosian showed a concentration dependent inhibitory effect on lipid peroxide (LPO) generation in vitro. Though celosian did not reduce the release of tumor necrosis factor-alpha (TNF-alpha), it protected against recombinant human TNF-alpha (rhTNF-alpha)-induced liver injury in D-galactosamine sensitized mice.
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PMID:Protective effect of celosian, an acidic polysaccharide, on chemically and immunologically induced liver injuries. 886 Sep 60

Ischemic hepatitis can occur as an acute episode in advanced congestive heart failure (CHF). The mechanism is massive necrosis of the central lobules resulting from acute hypoxia when low cardiac output further reduces oxygen supply, aggravating underlying congestion due to poor venous outflow. We describe a 70-year-old woman with congestive heart failure for 7 years who was admitted with jaundice, vomiting, abdominal pain and oliguria after an episode of hypotension. The diagnosis of ischemic hepatitis was established by a documented episode of severe hypotension, followed by elevation of serum transaminases, a rise in serum bilirubin and LDH levels, prolonged prothrombin time and acute renal failure. Other causes of acute hepatitis, such as a virus or drugs were excluded, and improved liver and renal function followed hemodynamic stabilization. We conclude that ischemic hepatitis should be considered whenever acute hepatitis follows a recent episode of systemic hypotension, especially in the context of concomitant CHF.
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PMID:[Ischemic hepatitis in congestive heart failure after an episode of hypotension]. 915 12

Sulofenur, a sulfonylurea, has demonstrated antitumour effect in preclinical studies. A phase I trial was initiated to study the clinical aspects. Sulofenur was given p.o. daily for a period of 28 days in 5-week courses. The initial dosage was 250 mg/m2 escalating to 700 mg/m2 daily with no dose modification for the individual patient at any given dose level; 38 patients with advanced solid malignant tumours were enrolled. Haemolytic anaemia was the main side effect. The toxicity was marked at dose levels of 600 and 700 mg/m2. Moderate methaemoglobinaemia also occurred. One case of reversible toxic hepatitis was observed. Generally was ALAT, and more moderately basic phosphatases, and LDH elevated. Tumour regression was not observed but one patient had stable disease throughout nine courses. The maximal detected plasma concentration of Sulofenur in this study was 348 x 10(-6) g/ml. In the present study the maximum tolerated dose (MTD) of Sulofenur was defined to 600 mg/m2. One conclusion from this study is that even at doses above that recommended for future studies-5-600 mg/m2-with this schedule, the suggested effective plasma level from preclinical studies could not be reached. The overall conclusion is that this schedule should not be recommended at all for future studies and the recommendation should be to try to find a schedule in which higher plasma levels can be achieved at a clinically tolerated dose.
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PMID:Early clinical investigation of sulofenur with a daily schedule in advanced solid tumours. 922 Feb 94


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