Chronic nitric oxide (NO) inhibition causes hypertension and renal injury. Concomitant salt overload promotes massive albuminuria. We investigated the mechanisms whereby these treatments impair glomerular permselectivity. Adult male Munich-Wistar rats received either a standard-salt (SS; 0.5% Na) or high-salt (HS; 3.1% Na) diet and either no treatment or the NO inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). At 30 days, albuminuria was moderate, the density of fixed anionic sites at the glomerular basement membrane (GBM), estimated by cationic ferritin binding, declined by approximately 35%, and the fractional clearance of 70-kDa neutral dextran (phi) rose moderately in rats receiving L-NAME and SS. Rats given L-NAME and HS exhibited massive albuminuria, whereas phi was nearly tripled. Depletion of GBM anionic sites was also seen in these rats. The GBM was thickened in both L-NAME-treated groups. These abnormalities were largely reversed after cessation of treatments. These results indicate that chronic L-NAME treatment promotes reversible albuminuria by impairing both glomerular size and charge selectivity. These effects likely reflect functional rather than structural disruption of the glomerular wall.
Mice selected on the basis of an acute inflammatory response (AIR) can provide information about the immunopathological mechanisms of glomerulonephritis. We studied the differences between mice selected for a maximal AIR (AIRmax that attract more polymorphonuclear cells to the site of injury) or a minimal AIR (AIRmin that attract more mononuclear cells) in an experimental model of IgA nephropathy in order to investigate the effect of genetic background on glomerular disease progression and the participation of the monocyte chemoattractant protein-1 (MCP-1) chemokine. IgA nephropathy was induced by intraperitoneal ovalbumin injection and bile duct ligation in AIRmax and AIRmin mice. Histological changes, urinary protein/creatinine ratio, serum IgA levels, immunofluorescence for IgA, IgG and complement C3 fraction, immunohistochemistry for macrophages and MCP-1, and MCP-1 levels in macerated kidney were determined. Mesangial IgA deposition was seen only in AIRmin mice, which presented more renal lesions. Increased serum IgA levels (1.5 ± 0.4 vs 0.3 ± 0.1 mg/mL, P < 0.001), high glomerular MCP-1 expression and decreased monocyte/macrophage infiltration in the interstitial area (0.3 ± 0.3 vs 1.1 ± 0.9 macrophages/field, P < 0.05) were detected in AIRmin mice compared to AIRmax mice. No glomerular monocyte/macrophage infiltration was detected in either strain. In spite of the absence of IgA deposition, AIRmax mice presented discrete or absent mesangial proliferation. The study showed that there are differences between mice selected for AIRmax and AIRmin with respect to serum IgA levels, histological damage and MCP-1 chemokine production after ovalbumin injection in combination with bile duct ligation.
Plasma albumin restricts capillary water filtration. Accordingly, the glomerular ultrafiltration coefficient is higher in Nagase analbuminemic rats (NAR) than in Sprague-Dawley controls. We investigated whether the glomerular permeability to macromolecules is also enhanced in NAR. SDS-PAGE fractionation of urine proteins showed several bands with molecular masses between 60 and 90 kDa in NAR only. Acute administration of BSA to NAR led to nearly complete disappearance of these proteins from urine, an effect partially reversed when most of the exogenous albumin was cleared from circulation. The fractional clearance of 70-kDa dextran was increased in NAR, indicating a size defect. Binding of cationized ferritin to the glomerular basement membrane was decreased in NAR, suggesting associated depletion of fixed anions. The magnitude of cationic ferritin binding correlated negatively with the fractional clearance of 70-kDa dextran, suggesting that the two abnormalities may share a common pathogenic mechanism. Collectively, these results suggest enhanced glomerular permeability to macromolecules in NAR. Albumin may be necessary to maintain the normal glomerular permselectivity properties.
BackgroundAn estimated 16.9% of adult Brazilian women experience sexual assault in their lifetime. Almost half of women who suffer such trauma develop post-traumatic stress disorder (PTSD). Markowitz et al. (2015) found that an affect-focused non-exposure therapy, Interpersonal Psychotherapy (IPT), adapted to treat PTSD (IPT-PTSD) had similar efficacy to and lower dropout rates than Prolonged Exposure (PE), the “gold standard,” most studied exposure therapy for PTSD.ObjectiveTo assess attrition rates in IPT of sexually assaulted women recently diagnosed with PTSD.MethodsThe current study derives from a two-arm, randomized controlled clinical trial of sexually assaulted women with PTSD who received 14 weeks of standardized treatment with either IPT-PTSD or sertraline. Sample: The 32 patients in the IPT treatment arm were analyzed.ResultsOverall attrition was 29%. One patient was withdrawn because of suicidal risk; four dropped out pre-treatment, and five dropped out during IPT-PTSD. If the excluded patient is considered a dropout, the rate increases to 31%.DiscussionThis is the first formal study of IPT for PTSD specifically due to sexual assault. IPT attrition approximated dropout rates in PE studies, which are often around 30%, and to the sertraline group in our study (34.5%). Further research should compare IPT and PE among sexually assaulted women to clarify our hypothesis that IPT could be an attractive alternative approach for this patient group.
RESUMO -o objetivo deste artigo foi investigar a prevalência do Transtorno Dissociativo de Identidade (TDI) em dez pacientes diagnosticados com esquizofrenia com característica paranóide, com base no Método de Rorschach. Foram registrados indicadores ou sintomas psicológicos que caracterizaram o diagnóstico diferencial desses pacientes, analisadas diferenças clínicas específicas e verificado o enquadramento dos dados obtidos, com a aplicação da Técnica de Rorschach. Para fins de diagnóstico diferencial, observou-se que dois pacientes apresentaram sintomas diferenciais aos da esquizofrenia, sendo que um deles apresentou sintomas dissociativos, não sendo confirmada a prevalência do TDI entre os esquizofrênicos. No caso da esquizofrenia e do TDI, devido às características similares que apresentam, avaliações multidisciplinares são indicadas para se fazer o diagnóstico diferencial entre eles. PALAVRAS-CHAVE: esquizofrenia, transtorno dissociativo de identidade, trauma, rorschach ABSTRACT -The aim of this article was to investigate the prevalence of the Dissociative Identity Disorder (DID) in ten patients diagnosed with schizophrenia with paranoid characteristic, based on the Rorschach approach. Psychological symptoms that characterize the differential diagnosis of these patients were registered, specific clinical differences were analyzed and the framework of the data obtained with the application of the Rorschach approach. For purposes of differential diagnosis, it was observed that two patients had differential symptoms to schizophrenia, one of which showed dissociative symptoms, not confirmed the prevalence of DID among schizophrenics. In the case of schizophrenia and DID due to exhibit similar characteristics, multidisciplinary evaluations are set to make a differential diagnosis between them.
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