Benzydamine induces apoptosis in astrocytes in vitro / Benzadamina induz apoptose em astrócitos in vitro

Objective: the present work aims to evaluate the Benzydamine (BZD) effect on cell viability in astrocyte culture and investigated the death mechanism involved with its cytotoxic effect. Methods: in order to evaluate cell viability, the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay was used, while flow cytometry was used to verify cell damage. The immunofluorescence assay was used to verify the expression of the marker's caspase-8, caspase9 and p65 subunit of Factor nuclear kappa B (NFκB). A statistical analysis for MTT assay and Flow Cytometry were made using ANOVA with Dunett's post-test; Student's t-test was made for the Immunofluorescence. Significance was set at p < 0.05. Results: the MTT reduction assay showed that BZD (3.1 to 100 µg/mL) caused a decrease in astrocytes viability. The flow cytometry showed that the cytotoxic effect of BZD was caused by the activation of the apoptotic death pathway, evidenced by the externalization of phosphatidylserine. The immunofluorescence revealed an increase in caspase-8 expression and no alteration in caspase-9 expression, demonstrating that there was an activation of the extrinsic pathway of apoptosis. The mean inhibitory concentration (IC50) of BZD (26.13 µg/mL) also caused an increase in NFκB p65 expression. Conclusion: taken together, the results of the present study suggest that BZD has a cytotoxic effect on astrocyte cells, and this effect comes from its ability to activate the extrinsic apoptotic pathway

Objetivo: o presente trabalho tem como objetivo avaliar o efeito da Benzidamina (BZD) na viabilidade celular em cultura de astrócitos e investigar o mecanismo de morte envolvido com seu efeito citotóxico. Métodos: para avaliar a viabilidade celular foi utilizado o ensaio de redução do brometo de 3-(4,5-Dimetiltiazol-2-il)-2,5-difeniltetrazólio (MTT), enquanto a citometria de fluxo foi utilizada para verificar o dano celular. O ensaio de imunofluorescência foi utilizado para verificar a expressão do marcador caspase-8, caspase9 e subunidade p65 do Fator nuclear kappa B (NFκB). A análise estatística para ensaio MTT e Citometria de Fluxo foi feita utilizando ANOVA com pós-teste de Dunett; Foi feito o teste t de Student para Imunofluorescência. A significância foi estabelecida em p < 0,05. Resultados: o ensaio de redução do MTT mostrou que o BZD (3,1 a 100 µg/mL) causou diminuição na viabilidade dos astrócitos. A citometria de fluxo mostrou que o efeito citotóxico do BZD foi causado pela ativação da via de morte apoptótica, evidenciada pela externalização da fosfatidilserina. A imunofluorescência revelou aumento na expressão de caspase-8 e nenhuma alteração na expressão de caspase-9, demonstrando que houve ativação da via extrínseca de apoptose. A concentração inibitória média (CI50) de BZD (26,13 µg/mL) também causou aumento na expressão de NFκB p65. Conclusão: em conjunto, os resultados do presente estudo sugerem que o BZD tem efeito citotóxico nas células astrocitárias, e esse efeito advém de sua capacidade de ativar a via apoptótica extrínseca.

Duchenne muscular dystrophy: RANK/RANKL/OPG (receptor activator of nuclear factor-kB/RANK ligand/osteoprotegerin) system and glucocorticoids / Distrofia muscular de Duchenne: el sistema RANK/RANKL/OPG (receptor activador del factor nuclear-kB/ligando de RANK/osteoprotegerina) y glucocorticoides

Abstract Duchenne muscular dystrophy (DMD) is an X-linked inherited disorder. Patients present with decreased bone mineral density (BMD) due to glucocorticoid therapy and progressive muscle weakness. Bone remodeling allows bone volume and structure to be maintained and controlled by local and systemic factors. These include the receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, a determining pathway in the balance between bone formation and resorption. Disruptions in this complex, caused by factors such as glucocorticoids, can affect bone metabolism. The extensive action of the RANK/RANKL/OPG pathway suggests an influence on dystrophic muscle pathophysiology. This review aimed to highlight some aspects of the RANK/RANKL/OPG system, the effect of glucocorticoids on this pathway, and the pathophysiology of the patient with DMD.

Resumen La distrofia muscular de Duchenne (DMD) es un trastorno hereditario ligado al cromosoma X. Los pacientes presentan una disminución de la densidad mineral ósea (DMO) debido a los efectos adversos del tratamiento con glucocorticoides y a la debilidad muscular progresiva. El remodelado óseo permite mantener el volumen y la estructura ósea, proceso controlado por factores locales y sistémicos. Entre ellos destaca el sistema del receptor activador del factor nuclear-kB (RANK), su ligando natural RANKL (RANKL) y la osteoprotegerina (OPG), una vía determinante en el equilibrio entre la resorción y formación ósea. Las alteraciones en este complejo, originadas por factores como los glucocorticoides, pueden afectar el metabolismo óseo. La amplia acción de RANKL y OPG ha sugerido una influencia en la fisiopatología de la DMD. El objetivo de esta revisión fue destacar algunos aspectos del sistema RANK/RANKL/OPG, el efecto de los glucocorticoides en esta vía y la fisiopatología del paciente con DMD.

Tumor adenomatoide de tubas uterinas, reporte de un caso y revisión de la literatura / Adenomatoid uterine tube tumor, case report and literature review

Resumen Los tumores adenomatoides del tracto genital son neoplasias poco frecuentes, de comportamiento benigno; debido a sus características histológicas se confunden fácilmente con tumores de estirpe vascular. Estudios recientes demuestran que los tumores adenomatoides del tracto genital femenino están genéticamente definidos por la mutación TRAF7 que activa la expresión aberrante de la vía NFkB. Presentamos el caso de una mujer de 27 años, asintomática, a quien se le realiza salpingectomía bilateral como método de anticoncepción definitivo; en el examen macroscópico de la tuba derecha se encuentra formación quística que por sus características microscópicas es diagnosticada como tumor adenomatoide de la tuba uterina. Finalmente se realiza una revisión de la literatura.

Abstract The adenomatoid tumors of the genital tract are rare neoplasms, with benign behavior; due to their histological characteristics, they are easily confused with tumors of vascular origin. Recent studies show that adenomatoid tumors of the female genital tract are genetically defined by the TRAF7 mutation that activates the aberrant expression of the NFkB pathway. We present the case of a 27-year-old woman, asymptomatic, who underwent bilateral salpingectomy as a method of definitive contraception; In the macroscopic examination of the right tuba, cystic formation is found which, due to its microscopic characteristics, is diagnosed as an adenomatoid tumor of the uterine tube. Finally, a review of the literature is made