Overexpression of urinary N-domain ACE in chronic kidney dysfunction in Wistar rats.

Local activation of the renin-angiotensin system (RAS) has been implicated in the pathogenesis of several renal disorders. In this study we investigated how chronic kidney disease (CKD) modulates RAS components in an experimental model. Male Wistar rats were divided into three groups: sham, nephrectomized, and nephrectomized receiving losartan. Chronic kidney disease animals presented decreased renal N-domain angiotensin-converting enzyme (ACE) activity but overexpression of N-domain ACE in urine. Remnant kidneys presented high angiotensin II levels. Losartan treatment increased urine and tissue ACE activity and tissue levels of angiotensins, mainly angiotensin (1-7), and improved renal and histopathologic parameters. Taken together, the authors' results indicate that pathophysiological changes due to CKD could lead to an increased expression of somatic and N-domain ACE, mainly the 65 kDa isoform, suggesting that this enzyme could be used as a biological urinary marker in CKD.

Metabolic profile of glycosaminoglycans in bladder and urethra of female rats during and after pregnancy.

INTRODUCTION AND HYPOTHESIS: The objective of this study is to evaluate pregnancy's action on glycosaminoglycans (GAGs) profile in bladder and urethra of female adult rats. METHODS: Twenty adult female rats were divided into four groups: control, day 10 pregnancy, day 20 pregnancy, and day 5 after delivery. Sulfated GAGs content were determined by densitometry. Hyaluronic acid was assessed by fluorimetric enzyme-linked immunosorbent serologic-like assay. Radioactive GAGs were quantified by measuring radioactivity in electrophoresis gel. Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney tests. RESULTS: In all groups, dermatan sulfate was predominant followed by heparan sulfate and hyaluronic acid. Significant decrease in total GAGs in bladder was observed at the beginning of pregnancy, with progressive increase. Biosynthesis of such molecules showed a similar behavior. In urethra, changes in GAGs content were restricted to the end of pregnancy. Hyaluronic acid content showed a significant increase in bladder during puerperium. CONCLUSIONS: We observed different composition in vesical and urethral tissues during pregnancy and in puerperium.

Tactile stimulation of adult rats modulates hormonal responses, depression-like behaviors, and memory impairment induced by chronic mild stress: Role of angiotensin II.

Physical touch can help to decrease the effects of stress. The aim of this study was to evaluate the influence of tactile stimulation on the hormonal and behavioral responses of young adult rats submitted to chronic mild unpredictable stress (CMS), considering the role of angiotensin II (Ang II). In Experiment 1, male rats were divided into 4 groups: control, stress, tactile stimulation (TS), and stress + TS. CMS was applied for three weeks. Tactile stimulation was applied for seven weeks, five days a week. After the CMS protocol, depression-like behaviors were evaluated by forced swimming and sucrose consumption tests. Learning and memory were evaluated using the Y-maze test. Fifteen days after the CMS procedure, the animals were euthanized and the levels of stress hormones were determined. The hypothalamus was isolated for determination of the Ang II concentration. In Experiment 2, control and stressed rats, with or without treatment using losartan (angiotensin II type 1 receptor blocker), were evaluated using the same behavioral tests and the hypothalamus Ang II concentration was also determined. CMS increased plasma corticosterone, norepinephrine, and epinephrine concentrations, induced depression-like behaviors, impaired learning and memory, and increased the Ang II concentration in the hypothalamus. Tactile stimulation attenuated these stress-induced effects. Losartan treatment effectively prevented increase of the hypothalamic Ang II concentration and the development of depression-like behavior, and also reduced the impairment of learning and memory in the stressed animals. The results indicated that tactile stimulation seemed to protect adult rats against hormonal and behavioral chronic stress effects, and that Ang II could be involved in the CMS effects.

[Prognostic value of plasmatic fibronectin and Child-Pugh classification in alcoholic cirrhotic patients. A comparative study]. / Valor prognóstico da fibronectina plasmática e da classifição de Child-Pugh na cirrose hepática alcoólica. Estudo comparativo.

BACKGROUND: To assess the prognostic value of plasmatic fibronectin (FN), compared to numeric Child-Pugh classification and its biochemical parameters in patients with alcoholic cirrhosis followed prospectively during a 18 months-period. METHODS: Fifty patients with the diagnosis of cirrhosis by hepatic biopsy or clinical and biochemical criteria, were included in the study after the exclusion of hepatocarcinoma and GI bleeding, infection or continous alcohol ingestion in the last 30 days. The mean age was 51.3+/-12.6 years, being 72% males and 17 of them were classified as Child-Pugh A, 18 as B and 15 as C. Serum bilirubin concentration was measured in autoanalyzer, protein electrophoresis was performed on cellulose acetate and prothrombin time by the Quick test. Plasmatic FN was assessed by radial immunodiffusion with anti-human FN in 1% agarose gel slabs. RESULTS: One patient was excluded because no natural death and 12 died owing to hepatic disease. The numeric Child-Pugh [score > 10, Relative Risk (RR)=11.33] and total bilirubins (> 2.5 mg/dL, RR=9.47) were the best predictors of death. Mean plasmatic FN concentration was significantly higher among those who survived when compared with those who died (185+/-66 mg/L x 131+/-38 mg/L, p<0.01), with a RR=6.59, for FN < 165 mg/L. Higher levels of FN, on the other hand, were the best variable to predict survival, since 96% of these 29 patients were alive at the end of follow-up. CONCLUSION: Although having less accuracy in predicting the risk of death of these patients, plasmatic FN > 165 mg/L was better predictor of survival than Child-Pugh score or any one of its biochemical parameters.

Valor prognóstico da fibronectina plasmática e da classificação de Child-Pugh na cirrose hepática alcoólica: estudo comparativo / Prognostic value of plasmatic fibronectin and Child-Pugh classification in alcoholic cirrhotic patients: a comparative study

OBJETIVOS: Avaliar o valor prognóstico da fibronectina plasmática (FN), comparativamente à classificação numérica de Child-Pugh e os parâmetros bioquímicos que a compõem, no acompanhamento prospectivo de portadores de cirrose alcoólica durante 18 meses. MÉTODOS: Incluídos 50 pacientes com cirrose alcoólica, diagnosticada por biópsia ou critérios clínico-bioquímicos, excluídos aqueles com hepatocarcinoma ou hemorragia digestiva, infecção ou ingestão alcoólica continuada nos últimos 30 dias. A idade média do grupo foi 51,3±12,6 anos, 72 por cento deles do sexo masculino e classificados 17 como Child-Pugh A, 18 como B e 15 como C. Os valores das bilirrubinas foram dosados pelo método automatizado, eletroforese de proteínas em acetato de celulose e o tempo de protrombina pelo método de Quick. A FN plasmática foi dosada por imunodifusão radial, com anticorpos contra FN humana em géis de agarose a 1 por cento. RESULTADOS: Um paciente foi excluído por óbito de causa não natural e 12 foram a óbito por doença hepática. Os melhores preditores de óbito foram a pontuação de Child-Pugh [escore>10, risco relativo (RR) de 11,33) e os valores de bilirrubina (>2,5mg/dL, RR=9,47). A concentração de FN foi significantemente maior nos sobreviventes que naqueles que foram a óbito (185±66 mg/L x 131±38mg/L, p<0,01), com RR = 6,59 para FN<165mg/L. Valores de FN acima desse valor de corte, entretanto, foram os melhores indicadores de sobrevida desde que 96,5 por cento desses 29 pacientes estavam vivos ao final de 18 meses de seguimento. CONCLUSAO: Embora apresente menor acurácia em predizer o risco de óbito desses pacientes, valores de FN plasmática> 165mg/L foram melhores indicadores de sobrevida que a classificação de Child-Pugh e seus parâmetros bioquímicos isolados.