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)

Little is known about the efficacy of flutamide monotherapy in previously untreated patients with prostatic carcinoma. In this study, 40 patients with advanced disease were treated with 250 mg flutamide, three times daily. The mean follow-up was 7 months. After 3 months, 35 patients were evaluable for efficacy; 17 showed a partial response and 18 showed no change. Tumor response after 6 months was evaluated in 22 patients; 10 had a partial response, nine had stable disease, and three had progression. The level of prostate-specific antigen was reduced markedly following 6 months' treatment with flutamide. Levels of testosterone increased slightly but significantly, and were still elevated not significant after a follow-up period of 1 year. Follicle-stimulating hormone did not change markedly, whereas luteinizing hormone rose significantly. Eighteen patients experienced mild gynecomastia and eight suffered diarrhea. In two patients, flutamide was discontinued for 2 weeks due to serious diarrhea. One patient was withdrawn after 6 weeks because of cholestatic hepatitis. Sexual potency was evaluated in 15 patients, 10 of whom remained sexually active during treatment. Flutamide monotherapy was concluded to be relatively safe and effective in patients with advanced prostatic cancer.
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PMID:Flutamide monotherapy as primary treatment in advanced prostatic carcinoma. 194 17

Hepatitis C virus (HCV) has an etiological role in post-transfusional Non-A Non-B Hepatitis, cirrhosis, and hepatoma. Studies have revealed an high prevalence of anti-HCV antibodies in hemophiliacs, IV drug users, and other groups at risk for parenterally transmitted infections. The authors report findings from their investigation into the sexual transmission of HCV. The prevalences of antibodies to HCV, the hepatitis B core (HBc) antigen, and to Treponema pallidum were assessed among groups of individuals at high and low risk for sexually transmitted diseases (STD). The population at low risk for STDs was comprised of 2494 volunteer blood donors at the Hospital Universitario Clementino Fraga Filho (HUCFF) over the period July-November 1990. The population at high risk for STDs was comprised of 187 adults consecutively enrolled between September 1990 and January 1991 in a cohort study of the natural history of HIV infection. Sera were screened with a first generation HCV ELISA test, with repeat reactive samples further analyzed using a second generation recombinant immunoblot confirmatory test (RIBA-2). Data on the presence of antibodies to HBc, VRDL, and HIV were abstracted from the Blood Bank records. Antibody testing against Treponema pallidum was conducted among HCV-ELISA positive blood donors and their controls using FTA-ABs. 2.08% of blood donors were infected with HCV, 7.96% of the HIV-infected homosexuals, and 8.02% of the whole group with sexually acquired HIV infection. Anti-HBc antibodies were more frequently present in anti-HCV RIBA-2 confirmed positive blood donors than in controls. 33.3% of the HCV-positive blood donors and 11.04% of controls were found to be anti-HBc positive. 17.6% of HCV-positive donors and 4.9% of controls yielded positive FTA-ABs results. 5.9% of samples from blood donors were both anti-HBc and FTA-ABs positive, while none of the controls reacted in both tests. The association between HCV, hepatitis B infection, and syphilis in individuals at low risk for parenterally transmitted diseases suggests that sexual transmission contributes to the maintenance of the endemicity of HCV in the local population.
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PMID:Prevalence of antibodies to hepatitis C virus in populations at low and high risk for sexually transmitted diseases in Rio de Janeiro. 750 22

The hepatotoxicity of flutamide, an antiandrogen that produces hepatitis in some human recipients, was studied in isolated rat hepatocytes. Flutamide (1 mM) led to the covalent binding of reactive electrophilic metabolites to male rat hepatocyte proteins. It decreased the reduced glutathione (GSH)/glutathione disulfide ratio and total protein thiols. This was associated with an early increase in phosphorylase a activity (a Ca(++)-dependent enzyme) and a decrease in cytoskeleton-associated protein thiols, the formation of plasma membrane blebs, the release of lactate dehydrogenase (LDH) and a loss of cell viability. Both covalent binding and LDH release were decreased by piperonyl butoxide (an inhibitor of cytochrome P450) and increased by dexamethasone pretreatment (which induces cytochrome P450 3A). The toxicity was increased by beta-naphthoflavone (which induces cytochrome P450 1A). Hepatocytes from female rats (which lack cytochrome P450 3A2) exhibited lower covalent binding and lower LDH release. The addition of cystine (a GSH precursor) increased hepatocellular GSH and decreased LDH release in male hepatocytes. The administration of a diet deficient in sulfur-containing amino acids had the opposite effects; it produced toxicity with 100 microM flutamide. Flutamide (50 microM) markedly inhibited respiration (mainly at the level of complex I) in isolated male rat liver mitochondria and flutamide (1 mM) decreased ATP levels in isolated male rat hepatocytes. It was concluded that flutamide is toxic to rat hepatocytes as a result of the cytochrome P450 (3A and also 1A)-mediated formation of electrophilic metabolites, whose damaging effects are further aggravated by the inhibitory effect of flutamide on mitochondrial respiration and ATP formation.
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PMID:Toxicity of the antiandrogen flutamide in isolated rat hepatocytes. 801 83

Flutamide, an oral nonsteroidal, antiandrogenic, anilid compound which inhibits the uptake and binding of androgens to nuclear receptors in the prostate, is used with or without LH-RH analogues for treatment of patients with metastatic carcinoma of the prostate. Clinically significant hepatotoxicities such as toxic hepatitis, cholestatic hepatitis, hepatic failure, and even death have rarely been reported in the English literature, but no case has been reported in Korea. A 75-year-old man with metastatic carcinoma of the prostate had taken flutamide (750 mg/day) for 7 months and suddenly developed jaundice and general weakness. The findings of blood chemistries were compatible with cholestatic hepatitis, but ultrasonography, viral marker and auto-antibody studies did not reveal any attributable causes. Histologic examination of a sono-guided liver biopsy only disclosed centrilobular cholestasis, nuclear glycogenosis and mild sinusoidal lymphocytic infiltration. Discontinuation of flutamide resulted in an almost full recovery of the patient's liver function in 2 months. We, herein, report a case of flutamide-induced acute choestatic hepatitis with a brief review of the literature.
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PMID:A case of flutamide-induced acute cholestatic hepatitis--a case report. 882 89

Flutamide is a nonsteroidal antiandrogen commonly used in the treatment of prostate cancer. Hepatic toxicity associated with flutamide has been reported with an incidence from less than 1% to about 5%. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been widely used in the treatment of cholesterol gallstones and of several liver diseases, but few data are now available concerning its use in the management of drug-induced hepatitis. The case of a patient who presented severe hepatitis with jaundice following use of flutamide is reported. UDCA treatment was started on admission and, contemporaneously, flutamide was withdrawn. Clinical and biochemical improvement was progressively observed, and the patient was discharged six weeks after the admission. Since fatal flutamide-related hepatitis has been reported, monitoring of serum liver tests is advocated during flutamide administration, and the effectiveness of UDCA in the treatment of drug-induced hepatotoxicity requires further study.
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PMID:Flutamide-induced toxic hepatitis. Potential utility of ursodeoxycholic acid administration in toxic hepatitis. 894 75

Flutamide is a nonsteroidal antiandrogen drug used in the treatment of prostatic cancer. Hepatotoxic reactions due to flutamide have been reported with an incidence ranging from 1% to 5%. These reactions are usually reversible upon withdrawal of the drug but can occasionally be life-threatening. The mechanism of flutamide-associated hepatotoxicity is not well established. We report a case of a 69-year-old man with prostatic carcinoma in whom flutamide induced an acute hepatitis which resolved completely soon after drug withdrawal. In this patient, we have studied the possible involvement of an immunological mechanism in causing flutamide hepatitis by investigating the presence of circulating antibodies directed against reactive metabolites of flutamide bound to liver proteins with enzyme-linked immunosorbent assay technique. Although, in the present case, we have failed to detect IgG reacting with rat liver microsomes incubated in vitro with flutamide, this does not completely rule out the possibility of an immunological involvement in flutamide hepatotoxicity. The possibility of severe flutamide-related injury, independently of the underlying pathogenic mechanism, strongly suggests the need for careful monitoring of liver enzymes in patients taking this drug.
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PMID:Flutamide-induced acute hepatitis: investigation on the role of immunoallergic mechanisms. 975 5

Sexually transmitted disease (STD) remains a major public health challenge in developed countries, exacerbated by the advent of the HIV epidemic. The objectives of this study were to assess the prevalence of serological markers of syphilis, HIV-1/2, HTLV-I/II, HBV, and HCV infections among immigrant sex workers in Madrid, Spain and to characterize the HIV-1 variants in seropositive individuals. Sera from 762 immigrant commercial sex workers (75.3% from sub-Saharan Africa, 18.2% from South America, and 6.4% from Eastern Europe) were collected between 1998 and 2003 in Madrid and examined. Antibody detection was performed by screening assays (RPR, ELISAs) and confirmed by FTA-Abs, LIAs and Western-blot tests. HIV-1 subtyping was carried out by phylogenetic analyses of the protease and envelope genes. Antibodies to HIV-1 were found in 5.2%, while 3.5% tested positive for HBsAg, 3% for syphilis antibodies, 0.8% for HCV antibodies, and 0.2% for HTLV-I antibodies. None were reactive for HIV-2 or HTLV-II antibodies. HIV-1 seroprevalence among Africans and Ecuadorians was 4.5 and 10.9%, respectively. All HIV-1 seropositive Ecuadorians were transsexual men, and 28.6% had active syphilis infection. Up to 80% of HIV-1 positive specimens were characterized as non-B subtypes, with subtypes G, A, and G/A recombinants being the most frequent among African individuals. In contrast, South Americans with HIV-1 infection carried exclusively subtype B variants. A relatively high proportion of immigrant sex workers in Madrid were infected with HIV-1 and syphilis, whereas infections with hepatitis viruses or HTLV were uncommon.
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PMID:Prevalence of HIV-1 non-B subtypes, syphilis, HTLV, and hepatitis B and C viruses among immigrant sex workers in Madrid, Spain. 1548 70

We report a case of secondary syphilis hepatitis in a liver-transplant patient. This homosexual male patient presented, 15 years after orthotopic liver transplantation, with non-squamous papulomacular rash, mild cytolysis, and anicteric cholestasis. Laboratory tests showed syphilis seroconversion with a venereal diseases research laboratory (VDRL) titer of 1/256, a Treponema pallidum hemaglutination assay (TPHA) of 1/5120, and a positive IgM fluorescent Treponemal antibody absorbance (FTA-abs). A liver biopsy performed 13 months after the diagnosis showed low-grade hepatitis with a Metavir score of A1F1; it also showed non-specific portal moderate inflammation consisting primarily of neutrophils, with no evidence of cholestasis. He was given benzathine-penicillin at 2,400,000 IU with a transient increase in prednisolone doses. Cytolysis rapidly, and cholestasis progressively disappeared. IgM FTA-abs became negative, whereas VDRL and TPHA titers decreased slightly over time.
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PMID:[Syphilis hepatitis and liver transplantation]. 1727 Mar 78

The non-steroidal antiandrogen flutamide is widely used for treatment of prostatic cancer, but causes side effects, including cholestatic hepatitis and fulminant hepatitis. We investigated the pathogenesis of flutamide-induced cholestatic hepatitis, focusing on the bile salt export pump (BSEP; ABCB11), which exports bile salts to the bile. We examined the inhibitory effects of flutamide and its active metabolite, hydroxyflutamide, on the transport of taurocholic acid (TCA) by membrane vesicles derived from hBSEP-expressing Sf9 cells. Flutamide inhibited the transport of TCA by hBSEP (IC50 value, about 50 microM), while hydroxyflutamide had no effect at up to 100 microM. When flutamide was administered to rats as a single oral dose of 100 mg/kg, the biliary excretion rate of bolus-injected [3H]TCA was decreased and the liver tissue concentration of flutamide exceeded 50 microM. Repeated doses of flutamide for 5 d (10 mg/kg/d) also decreased the biliary excretion rate of bolus-injected [3H]TCA. In this case, the liver tissue concentration of flutamide was below 0.1 microM. In both cases, no change in the mRNA level of rat Bsep was detected by RT-PCR. These results suggest that flutamide itself, but not its major metabolite, may cause cholestasis by inhibiting BSEP-mediated bile salt excretion.
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PMID:Involvement of bile salt export pump in flutamide-induced cholestatic hepatitis. 1740 13

The feasibility of using liver impressions on Flinders Technology Associates (FTA filter paper for the collection, inactivation, and molecular analysis of fowl adenovirus (FAV) was evaluated. FAV I European Union (EU) serotype 1 spotted on FTA was shown to be inactivated using specific-pathogen-free (SPF) primary chicken embryo liver cell culture as indicated by absence of cytopathic effect. Sensitivity of the polymerase chain reaction (PCR) test using tenfold dilutions of allantoic fluid from 100 to 10-4 for the detection of adenovirus serotype 1 on FTA cards was determined to be 0.0005 mean tissue culture infectious dose per FTA spot. The stability of the DNA from liver impressions on the FTA was found to be 198 days when stored at -20 degrees C. In a trial, inclusion body hepatitis (IBH) was experimentally reproduced in SPF chickens inoculated with FAV I EU serogroup 1, 4, 8, or 11, which presented weakness, pallor, depression, dehydration, and mortality within 6 days after inoculation. PCR performed on FTA liver impressions from the inoculated birds was able to detect all four viruses, and the nucleotide sequence analysis of the amplified PCR products (1219 bp of the hexone gene) revealed the expected serotypes. In addition to the trial, 55 clinical samples were analyzed from liver impressions on FTA cards, and FAV was detected in 11 of 55 (20%). Sequencing analysis showed that the viruses were EU serotypes 4, 5, 9, and 10. The results demonstrate that FTA filter paper inactivates the FAV I and maintains the DNA template for molecular analysis.
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PMID:FTA liver impressions as DNA template for detecting and genotyping fowl adenovirus. 1746 Dec 76


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