RESUMO
Plasmodium falciparum has exerted tremendous selective pressure on genes that improve survival in severe malarial infections. Systemic lupus erythematosus (SLE) is an autoimmune disease that is six to eight times more prevalent in women of African descent than in women of European descent. Here we provide evidence that a genetic susceptibility to SLE protects against cerebral malaria. Mice that are prone to SLE because of a deficiency in FcγRIIB or overexpression of Toll-like receptor 7 are protected from death caused by cerebral malaria. Protection appears to be by immune mechanisms that allow SLE-prone mice better to control their overall inflammatory responses to parasite infections. These findings suggest that the high prevalence of SLE in women of African descent living outside of Africa may result from the inheritance of genes that are beneficial in the immune control of cerebral malaria but that, in the absence of malaria, contribute to autoimmune disease.
Assuntos
População Negra/genética , Predisposição Genética para Doença/genética , Lúpus Eritematoso Sistêmico/genética , Malária Cerebral/genética , Plasmodium berghei/imunologia , Receptores de IgG/deficiência , Receptor 7 Toll-Like/metabolismo , Animais , Encéfalo/imunologia , Encéfalo/patologia , Citocinas/sangue , Primers do DNA/genética , Ensaio de Imunoadsorção Enzimática , Eritrócitos/parasitologia , Feminino , Citometria de Fluxo , Humanos , Lúpus Eritematoso Sistêmico/etnologia , Malária Cerebral/imunologia , Malária Cerebral/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Tamanho do Órgão , Receptores de IgG/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Baço/fisiologia , Análise de SobrevidaAssuntos
Varizes Esofágicas e Gástricas/diagnóstico por imagem , Hematemese/etiologia , Hipertensão Portal/diagnóstico por imagem , Veia Porta/anormalidades , Adolescente , Doença Crônica , Endoscopia do Sistema Digestório , Varizes Esofágicas e Gástricas/complicações , Humanos , Hipertensão Portal/complicações , Masculino , Veia Porta/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Purpose: Intravesical electrical stimulation treatment (IVES) has been successfully used to treat neurogenic bladder. We report the results of an observational study regarding the use of IVES for women with overactive bladder syndrome (OAB) and/or urgency urinary incontinence (UUI). Materials and Methods: IVES was performed in women with OAB (defined by frequency ≥8/day, nocturia ≥2/night, or ≥3 episodes of UUI on 3-day voiding diary) who failed prior medical therapy. Subjects underwent 4 weeks of treatment with an 8-Fr Detruset™ IVES catheter. Primary outcome was Patient Global Impression of Improvement (PGI-I) at 3 months. Secondary outcomes included Visual Analog Scale (VAS), Short Form OAB Questionnaire (OAB-q SF), Pelvic Floor Distress Inventory (PFDI), Pelvic Floor Impact Questionnaire (PFIQ), reduction in frequency and UUI on voiding diary, and adverse effects. Analysis was done with paired t-tests and Wilcoxon signed rank tests. Results: Seventeen subjects completed the study. At 4 weeks post-treatment, 15 improved on PGI-I (11 subjects: 'a little better', 2: 'much better', 2: 'very much better'). There were significant improvements in symptom bother and health-related quality of life as measured by OAB-q SF and pelvic organ prolapse and urinary distress as measured by PFDI. Frequency decreased from 10.3±4.3 at baseline to 8.9±2.3 (p=0.04) at 3 months. No pain was reported during treatment. There was one urinary tract infection during the study period. No other adverse events were reported. Conclusions: IVES appears to be a safe and effective novel treatment for OAB. Larger comparative studies are needed to investigate its potential for long-term treatment.