RESUMO
INTRODUCTION: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD. METHODS: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. RESULTS: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. CONCLUSIONS: The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD.
Assuntos
Selectina E/fisiologia , Endotélio/fisiopatologia , Molécula 1 de Adesão Intercelular/fisiologia , Dengue Grave/sangue , Dengue Grave/fisiopatologia , Molécula 1 de Adesão de Célula Vascular/fisiologia , Adolescente , Adulto , Antígenos CD/sangue , Antígenos CD/fisiologia , Antígenos Virais/sangue , Biomarcadores/sangue , Caderinas/sangue , Caderinas/fisiologia , Criança , Pré-Escolar , Progressão da Doença , Selectina E/sangue , Feminino , Humanos , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Regulação para Cima , Molécula 1 de Adesão de Célula Vascular/sangue , Adulto JovemRESUMO
Abstract INTRODUCTION: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD. METHODS: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. RESULTS: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. CONCLUSIONS: The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto , Adulto Jovem , Molécula 1 de Adesão Intercelular/fisiologia , Molécula 1 de Adesão de Célula Vascular/fisiologia , Selectina E/fisiologia , Dengue Grave/fisiopatologia , Dengue Grave/sangue , Endotélio/fisiopatologia , Imuno-Histoquímica , Biomarcadores/sangue , Antígenos CD/fisiologia , Antígenos CD/sangue , Caderinas/fisiologia , Caderinas/sangue , Regulação para Cima , Molécula 1 de Adesão Intercelular/sangue , Progressão da Doença , Molécula 1 de Adesão de Célula Vascular/sangue , Selectina E/sangue , Pessoa de Meia-Idade , Antígenos Virais/sangueRESUMO
ABSTRACT Introduction: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. Materials and Methods: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration. Transforming growth factor beta-1 (TGF-β1), E-cadherin, nitric oxide (NO) and hydroxyproline levels were measured. Histopathological and immunohistochemical examinations were carried out. Results: TGF-β1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group. In rats treated with UUO + OPZ, despite the presence of mild tubular degeneration and less severe tubular necrosis, glomeruli maintained a better morphology when compared to the UUO group. Expressions of α-SMA in immunohistochemistry showed that the staining positivity decreased in the tubules of the OPZ-treated group. Conclusions: While the precise mechanism of action remains unknown, our results demonstrated that OPZ exerted a protective role in the UUO-mediated renal fibrosis rat model highlighting a promising therapeutic potency of Nrf2-activators for alleviating the detrimental effects of unilateral obstruction in kidneys.
Assuntos
Animais , Masculino , Ratos , Pirazinas/uso terapêutico , Obstrução Ureteral/complicações , Fator 2 Relacionado a NF-E2/uso terapêutico , Nefropatias/tratamento farmacológico , Tionas , Tiofenos , Obstrução Ureteral/patologia , Obstrução Ureteral/tratamento farmacológico , Fibrose/etiologia , Fibrose/tratamento farmacológico , Imuno-Histoquímica , Caderinas/sangue , Ratos Wistar , Modelos Animais de Doenças , Fator de Crescimento Transformador beta1/sangue , Hidroxiprolina/sangue , Nefropatias/etiologia , Nefropatias/patologia , Óxido Nítrico/sangueRESUMO
INTRODUCTION: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. MATERIALS AND METHODS: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration. Transforming growth factor beta-1 (TGF-ß1), E-cadherin, nitric oxide (NO) and hydroxyproline levels were measured. Histopathological and immunohistochemical examinations were carried out. RESULTS: TGF-ß1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group. In rats treated with UUO + OPZ, despite the presence of mild tubular degeneration and less severe tubular necrosis, glomeruli maintained a better morphology when compared to the UUO group. Expressions of α-SMA in immunohistochemistry showed that the staining positivity decreased in the tubules of the OPZ-treated group. CONCLUSIONS: While the precise mechanism of action remains unknown, our results demonstrated that OPZ exerted a protective role in the UUO-mediated renal fibrosis rat model highlighting a promising therapeutic potency of Nrf2-activators for alleviating the detrimental effects of unilateral obstruction in kidneys.
Assuntos
Nefropatias/tratamento farmacológico , Fator 2 Relacionado a NF-E2/uso terapêutico , Pirazinas/uso terapêutico , Obstrução Ureteral/complicações , Animais , Caderinas/sangue , Modelos Animais de Doenças , Fibrose/tratamento farmacológico , Fibrose/etiologia , Hidroxiprolina/sangue , Imuno-Histoquímica , Nefropatias/etiologia , Nefropatias/patologia , Masculino , Óxido Nítrico/sangue , Ratos , Ratos Wistar , Tionas , Tiofenos , Fator de Crescimento Transformador beta1/sangue , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/patologiaRESUMO
We aimed at investigating the association between metabolic syndrome (MS) and vascular endothelial cell dysfunction (ECD) in children and adolescents. Sixty children (30 obese children and 30 children with MS) were included in this retrospective analysis. Thirty healthy subjects were randomly selected as the control group. A series of indices/biomarkers known to be related to MS/ECD were determined using ELISA. Correlations between the variables measured were analyzed. Compared with the control group, PAI-1, vWF, VE-cad, TM, and VEGF were significantly increased in the MS group (P < 0.05). Adolescents in the obese group had significantly increased levels of serum PAI-1, VE-cad, TM, and VEGF as compared with the control group (P < 0.05). Further, vWF in the obese and control groups did not differ significantly (P = 0.556). Our results suggest that ECD is correlated with MS in children and adolescents. Pathophysiological changes of the vascular endothelium may exist in obese children who have yet to develope MS. PAI-1, vWF, VE-cad, TM, and VEGF could be used as biomarkers for predicting ECD. ECD that develops in patients with MS may be associated with obesity, elevated blood lipid, elevated blood glucose, and higher blood pressure.
Assuntos
Endotélio Vascular/metabolismo , Síndrome Metabólica/sangue , Adolescente , Biomarcadores/sangue , Caderinas/sangue , Estudos de Casos e Controles , Criança , Endotélio Vascular/fisiopatologia , Humanos , Obesidade/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Trombomodulina/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Fator de von Willebrand/análiseRESUMO
Numerous hypotheses have been proposed about the pathogenesis of the polycystic ovarian syndrome (PCOS). However, hormonal control of persistent follicles has not been established. The objective of the present study was to compare the follicular structure and hormonal profiles of rats treated with the adrenocorticotrophic hormone (ACTH) with two experimental models of PCOS. ACTH-treated animals were compared with those exposed to continuous light, those treated with estradiol valerate, and with control (in proestrous and diestrous). Serum hormone levels, histomorphometrical changes, and immunoexpression of vimentin, cytokeratins, cadherins, and proliferating cell nuclear antigen (PCNA) were examined. Treatment with ACTH resulted in an elevation of corticosterone secretion with LH reduction but without changes in ovarian morphology. Although stress (or ACTH) stimulation may be only one of pathophysiological mechanisms involved in follicular cyst pathogenesis in other species, we do not have important evidence to suppose that this would happen in rats.
Assuntos
Hormônio Adrenocorticotrópico/fisiologia , Hormônios/sangue , Ovário/patologia , Síndrome do Ovário Policístico/patologia , Síndrome do Ovário Policístico/fisiopatologia , Animais , Caderinas/sangue , Proliferação de Células , Corticosterona/sangue , Ciclo Estral/fisiologia , Feminino , Hormônios Esteroides Gonadais/sangue , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Queratinas/metabolismo , Folículo Ovariano/patologia , Antígeno Nuclear de Célula em Proliferação/sangue , Ratos , Ratos Wistar , Vimentina/metabolismoRESUMO
OBJECTIVE: The aim of the present study was to investigate a broad spectrum of autoantibodies in patients with endemic pemphigus foliaceus (EPF)-fogo selvagem-and to determine the possible association between EPF and other autoimmune diseases. MATERIALS AND METHODS: Indirect immunofluorescence was used to test 120 patients with EPF and 200 healthy controls for the presence of the following autoantibodies: anti-desmoglein-1 (APF), anti-neutrophil cytoplasmic (ANCA), anti-smooth muscle (SMA), anti-mitochondrial (AMA), anti-nuclear (ANA), anti-liver kidney microsomal (LKM), anti-gastric parietal cells (GPCA) and anti-thyroid microsome (TMA). RESULTS: APF antibodies were detected in 62.5% of the patients (75/120), ANA and SMA in 0.8% (1/120), and TMA in 1.6% (2/120). None of the patients was positive for ANCA, AMA, LKM or GPCA. In the control group, a positivity of 2% was observed for SMA (4/200), 1.5% for TMA (3/200), and 0.5% (1/200) for ANA and GPCA. None of the controls was positive for APF, LKM, AMA or ANCA. CONCLUSIONS: The prevalence of the autoantibodies ANA, SMA, AMA, GPCA, LKM and ANCA in patients with EPF was similar to that observed in the control group. No association with clinical or laboratory manifestations of other concomitant autoimmune diseases was observed in EPF patients. These results confirm the concept that EPF is an organ-specific autoimmune disease.