Autoimmune hepatitis triggered by nitrofurantoin: a case series

<p>Abstract</p> <p>Introduction</p> <p>Drugs can occasionally trigger the onset of autoimmune liver disease.</p> <p>Case presentation</p> <p>Three Caucasian women (aged 65, 42 and 74 years old) who were receiving long-term nitrofurantoin as prophylaxis against recurrent urinary tract infections developed hepatitic liver disease. Serological auto-antibody profiles and liver histology appearances were consistent with autoimmune hepatitis. Two of the patients presented with jaundice, and one required a prolonged hospital admission for liver failure. In all three patients nitrofurantoin was withdrawn, and long-term immunosuppressive therapy with prednisolone and azathioprine or mycophenolate was given. The patients responded well, with liver biochemistry returning to normal within a few months.</p> <p>Conclusions</p> <p>Although nitrofurantoin rarely causes autoimmune hepatitis, this antimicrobial is increasingly used as long-term prophylaxis against recurrent urinary tract infection. General practitioners and urologists who prescribe long-term nitrofurantoin therapy should be aware of this adverse effect.</p

Anticancer Activities of Six Selected Natural Compounds of Some Cameroonian Medicinal Plants

BACKGROUND: Natural products are well recognized as sources of drugs in several human ailments. In the present work, we carried out a preliminary screening of six natural compounds, xanthone V(1) (1); 2-acetylfuro-1,4-naphthoquinone (2); physcion (3); bisvismiaquinone (4); vismiaquinone (5); 1,8-dihydroxy-3-geranyloxy-6-methylanthraquinone (6) against MiaPaCa-2 pancreatic and CCRF-CEM leukemia cells and their multidrug-resistant subline, CEM/ADR5000. Compounds 1 and 2 were then tested in several other cancer cells and their possible mode of action were investigated. METHODOLOGY/FINDINGS: The tested compounds were previously isolated from the Cameroonian medicinal plants Vismia laurentii (1, 3, 4, 5 and 6) and Newbouldia laevis (2). The preliminary cytotoxicity results allowed the selection of xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, which were then tested on a panel of cancer cell lines. The study was also extended to the analysis of cell cycle distribution, apoptosis induction, caspase 3/7 activation and the anti-angiogenic properties of xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone. IC(50) values around or below 4 µg/ml were obtained on 64.29% and 78.57% of the tested cancer cell lines for xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, respectively. The most sensitive cell lines (IC(50)<1 µg/ml) were breast MCF-7 (to xanthone V(1)), cervix HeLa and Caski (to xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone), leukemia PF-382 and melanoma colo-38 (to 2-acetylfuro-1,4-naphthoquinone). The two compounds showed respectively, 65.8% and 59.6% inhibition of the growth of blood capillaries on the chorioallantoic membrane of quail eggs in the anti-angiogenic assay. Upon treatment with two fold IC(50) and after 72 h, the two compounds induced cell cycle arrest in S-phase, and also significant apoptosis in CCRF-CEM leukemia cells. Caspase 3/7 was activated by xanthone V(1). CONCLUSIONS/SIGNIFICANCE: The overall results of the present study provided evidence for the cytotoxicity of compounds xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, and bring supportive data for future investigations that will lead to their use in cancer therapy

Thalidomide in the treatment of erythema nodosum leprosum (ENL): systematic review of clinical trials and prospects of new investigations

FUNDAMENTOS: A hanseníase persiste como problema de saúde pública, e episódios de ENH são eventos agudos que ocorrem antes, durante e após PQT. Na última década, o uso da talidomida como agente imunomodulador foi expandido a outras doenças. OBJETIVOS: realizar revisão sistemática dos ensaios clínicos publicados sobre a eficácia e efeitos colaterais da talidomida no ENH. Descrever metodologia e resultados da triagem para recrutamento de ensaio clínico visando avaliar dose-resposta da talidomida seguida de desmame no ENH moderado e grave, realizado no Brasil. MÉTODOS: Analisaram-se ensaios publicados sobre talidomida no ENH. Foi delineado um ensaio clínico duplo-cego randomizado para avaliar dose de 100 thalid 300mg/dia de talidomida durante fase aguda de ENH, seguida de desmame da talidomida, thalid placebo. Para este ensaio clínico descreve-se metodologia e dados de recrutamento de pacientes, com ênfase na gravidade dos episódios de ENH. RESULTADOS: Os seis ensaios clínicos publicados nas décadas de 1960 e 1970 apontam para o benefício da talidomida no ENH, embora diferenças metodológicas dificultem a comparação. Na fase de recrutamento do ensaio brasileiro, dos 143 pacientes de ENH triados, 65% eram potencialmente elegíveis. A associação com neurite em 56,4% dos ENH moderados e graves exigiu co-intervenção com corticosteróide. CONCLUSÃO: O padrão de recrutamento dos pacientes evidenciou alta freqüência de neurite nos episódios de ENH. O esquema de talidomida isolada no ENH foi avaliado como infreqüente na prática clínica brasileira. O desafio atual é acumular evidências sobre a eficácia e efeitos colaterais da talidomida em associação com corticosteróides.BACKGROUND: Leprosy remains a public health problem. Episodes of erythema nodosum leprosum (ENL) are acute events that occur before, during and after polychemotherapy. In the last decade, the use of thalidomide as an immunomodulating agent was expanded to other diseases. OBJECTIVES: To perform a systematic review of published clinical trials on efficacy and side effects of thalidomide in ENL. To describe the methodology and screening results of recruiting for a clinical trial performed in Brazil, which aimed to assess the dose-response of thalidomide followed by tapering regimen in severe and moderate cases of ENL. METHODS: Published clinical trials on the use of thalidomide in ENL were analyzed. A randomized, double-blind clinical trial was designed to evaluate the doses of 100mg versus 300mg/day thalidomide during the acute stage of ENL, followed by thalidomide tapering regimen versus placebo. For this clinical trial, the methodology and data for enrollment of patients were described, with an emphasis on severity of ENL episodes. RESULTS: Six clinical trials published in the 1960's and 1970's indicated the benefits of thalidomide in ENL, although methodological differences made comparison difficult. In the enrollment stage of the Brazilian trial, 65% of patients were potentially eligible out of 143 ENL patients screened. The association with neuritis in 56.4% of moderate and severe cases of ENL required the co-intervention with steroids. CONCLUSION: The patients' enrollment pattern demonstrated high frequency of neuritis in ENL episodes. The treatment regimen with thalidomide in monotherapy for ENL was considered infrequent in the clinical practice in Brazil. The current challenge is to accumulate evidence about efficacy and side effects of thalidomide in combination with steroids