RESUMO
Aim: Mitochondrial DNA (mtDNA) alterations play an important role in the multistep processes of cancer development. Gliomas are among the most diagnosed brain cancer. The relationship between mtDNA alterations and different grades of gliomas are still elusive. This study aimed to elucidate the profile of somatic mtDNA mutations in different grades of gliomas and correlate it with clinical phenotype. Materials & methods: Forty histopathologically confirmed glioma tissue samples and their matched blood were collected and subjected for mtDNA sequencing. Results & conclusion: About 75% of the gliomas harbored at least one somatic mutation in the mtDNA gene, and 45% of these mutations were pathogenic. Mutations were scattered across the mtDNA genome, and the commonest nonsynonymous mutations were located at complex I and IV of the mitochondrial respiratory chain. These findings may have implication for future research to determine the mitochondrial energetics and its downstream metabolomics on gliomas.
Assuntos
Genoma Mitocondrial , Glioma , DNA Mitocondrial/genética , Glioma/genética , Humanos , Mitocôndrias/genética , Mutação/genéticaRESUMO
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
BACKGROUND: External ventricular drainage (EVD) has been widely used for the purpose of cerebrospinal fluid (CSF) diversion at Hospital Kuala Lumpur (HKL). METHOD: This prospective observational study was conducted in HKL from December 2006 to December 2008 among patients who were subjected for EVD, following strict inclusion and exclusion criteria. RESULTS: The frequency of EVD-related infection was as high as 32.2% (95% CI 23.3% to 42.57%) among 87 patients studied. This study clearly demonstrates that tunnelling the catheter for more than 5 cm under the scalp, from the burr hole to the exit site of the skin, carried a significantly lower risk of infection compared with tunnelling the catheter for 5 cm or less (OR = 0.184, 95% CI 0.083 to 0.406, P < 0.001). The majority of cases (19 out of 28) with EVD-related infection occurred among patients catheterised for more than 10 days (OR = 0.334, 95% CI 0.171 to 0.652, P < 0.001). CONCLUSION: The technique of subgaleal tunnelling of more than 5cm and the duration of the ventricular catheterisation of 10 days and less should be implemented as standardised protocol at health institutions to reduce the risk of EVD-related infections.