RESUMO
INTRODUCTION: Erectile dysfunction is considered an early clinical manifestation of vascular disease and an independent risk factor for cardiovascular events associated with endothelial dysfunction and increased levels of pro-inflammatory cytokines. Tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, suppresses endothelial nitric oxide synthase (eNOS) expression. AIM: Considering that nitric oxide (NO) is of critical importance in penile erection, we hypothesized that blockade of TNF-alpha actions would increase cavernosal smooth muscle relaxation. METHODS: In vitro organ bath studies were used to measure cavernosal reactivity in wild type and TNF-alpha knockout (TNF-alpha KO) mice and NOS expression was evaluated by western blot. In addition, spontaneous erections (in vivo) were evaluated by videomonitoring the animals (30 minutes). Collagen and elastin expression were evaluated by Masson trichrome and Verhoff-van Gieson stain reaction, respectively. MAIN OUTCOME MEASURES: Corpora cavernosa from TNF-alpha KO mice exhibited increased NO-dependent relaxation, which was associated with increased eNOS and neuronal NOS (nNOS) cavernosal expression. RESULTS: Cavernosal strips from TNF-alpha KO mice displayed increased endothelium-dependent (97.4 +/- 5.3 vs. CONTROL: 76.3 +/- 6.3, %) and nonadrenergic-noncholinergic (93.3 +/- 3.0 vs. CONTROL: 67.5 +/- 16.0; 16 Hz) relaxation compared to control animals. These responses were associated with increased protein expression of eNOS and nNOS (P < 0.05). Sympathetic-mediated (0.69 +/- 0.16 vs. CONTROL: 1.22 +/- 0.22; 16 Hz) as well as phenylephrine-induced contractile responses (1.6 +/- 0.1 vs. CONTROL: 2.5 +/- 0.1, mN) were attenuated in cavernosal strips from TNF-alpha KO mice. Additionally, corpora cavernosa from TNF-alpha KO mice displayed increased collagen and elastin expression. In vivo experiments demonstrated that TNF-alpha KO mice display increased number of spontaneous erections. CONCLUSION: Corpora cavernosa from TNF-alpha KO mice display alterations that favor penile tumescence, indicating that TNF-alpha plays a detrimental role in erectile function. A key role for TNF-alpha in mediating endothelial dysfunction in ED is markedly relevant since we now have access to anti-TNF-alpha therapies.
Assuntos
Disfunção Erétil/imunologia , Disfunção Erétil/terapia , Músculo Liso/imunologia , Fator de Necrose Tumoral alfa/imunologia , Vasodilatação/fisiologia , Animais , Colágeno/metabolismo , Elastina/metabolismo , Endotélio Vascular/imunologia , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Disfunção Erétil/metabolismo , Masculino , Camundongos , Camundongos Knockout , Músculo Liso/metabolismo , Músculo Liso/patologia , Óxido Nítrico Sintase/metabolismo , PênisRESUMO
Hemodialized pediatric patients are a risk population for the hepatitis B and C virus infection. The aim of this paper was to study the serum prevalence of HBV and HCV infection in hemodialized children. We study 61 pediatric patients at hemodialisis, 12 on renal transplant, range between 2 and 20 years old (mean: 12.9 years), 23 male and 38 female. The specific anti-HCV IgC were measured by enzyme immunoassay (ELISA Abbott) and confirmed by LIA-TEK (Organon). The anti-HBV were measured by ELISA Abbott and transaminases by cinetic method (ASAT: 29 UI/L and ALT: 33 UI/L). The 19.7% of studied children were HCV (+) and 29.5% were HBV (+), 38.9% of them were HbsAg (+) and 50% anti-HBs (+). The HCV and HBV infection was more elevated in relation to the transfusion number and the hemodilisis time. The elevation of ALT/ASAT activity isn't a right infection index for HCV and HBV in this children.
Assuntos
Anticorpos Anti-Hepatite B/isolamento & purificação , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite C/isolamento & purificação , Hepatite C/epidemiologia , Diálise Renal , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Prevalência , Estudos SoroepidemiológicosRESUMO
A phase II study of advanced FIGO III and IV ovarian cancer treated with carboplatin and ifosfamide was performed to define the efficacy and tolerability of this regimen as first-line chemotherapy. From November 1990 to December 1994, 30 women with advanced ovarian cancer or residual disease after initial surgery were treated with carboplatin (300 mg/m(2) intravenously on day 1) and ifosfamide (1,500 mg/m(2) intravenously on days 1-3, with MESNA) every 3 weeks. The overall response rate was 67% (complete response 27%, partial response 40%) and the median duration of response was 14 months (range, 6-36). After a median follow-up of 31 months, the median survival was 24.9 months. Time to progression (p<0.05) and overall survival were longer in the patient group subjected to debulking. This regimen was easily manageable with good activity and acceptable toxicity, and most patients were treated on an outpatient basis.