RESUMO
The present study aimed to investigate the involvement of the angiogenic marker vascular endothelia growth factor (VEGF) and apoptotic markers of Bcl-2 and Bax in the neurons and astrocytes in the brain infected by Mycobacterium tuberculosis. The immunohistochemistry staining was performed to analyze the expression of the VEGF, Bcl-2 and Bax in the astrocytes and neurons. The expression of VEGF was high in neurons and astrocytes in both the infected brain and control tissues with no difference of angiogenic activity (pâ¯=â¯0.40). Higher Bcl-2 expression was seen in astrocytes of infected brain tissues compared to the control tissues (pâ¯=â¯0.004) promoted a higher anti-apoptotic activity in astrocytes. The neurons expressed strong Bax expression in the infected brain tissues compared to the control tissues (pâ¯<â¯0.001), which indicated more apoptosis in neurons. Thus, neuronal death and survival of infected astrocytes together with high expression of VEGF might be associated with formation of brain tuberculosis. In conclusion, neurons could be more vulnerable than astrocytes in human tuberculosis brain with high expression of VEGF.
Assuntos
Apoptose , Astrócitos/metabolismo , Mycobacterium tuberculosis/patogenicidade , Neurônios/metabolismo , Tuberculose do Sistema Nervoso Central/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Astrócitos/microbiologia , Astrócitos/patologia , Estudos de Casos e Controles , Humanos , Neurônios/microbiologia , Neurônios/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Tuberculose do Sistema Nervoso Central/microbiologia , Tuberculose do Sistema Nervoso Central/patologia , Regulação para Cima , Proteína X Associada a bcl-2/metabolismoRESUMO
PURPOSE: The importance of HLA-B*15:02 genotyping to avoid carbamazepine induced SJS/TEN and molecular modeling to predict the role of HLA-B*15:0 and AEDs induced SJS/TEN are investigated. METHODS: DNA was extracted from eighty-six patients. The patients were genotyped by AS-PCR. Computational modeling of the HLA-B*15:02 followed by docking studies were performed to screen 26 AEDs that may induce ADR among HLA-B*15:02 carriers. RESULTS: Odd ratio for CBZ induced SJS/TEN and HLA-B*15:02 was 609.0 (95% CI: 23-15873; p=0.0002). Molecular modeling studies showed that acetazolamide, ethosuxiamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone and sodium-valproate may induce ADR in HLA-B*15:02 carriers alike CBZ. Conclusion. We confirmed HLA-B*15:02 as a predictor of SJS/TEN and recommend pre-screening. Computational prediction of DIHR is useful in personalized medicine.