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Báo cáo y học: "Successful tumour necrosis factor (TNF) blocking therapy suppresses oxidative stress and hypoxiainduced mitochondrial mutagenesis in inflammatory arthritis"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài:Successful tumour necrosis factor (TNF) blocking therapy suppresses oxidative stress and hypoxiainduced mitochondrial mutagenesis in inflammatory arthritis. | Biniecka et al. Arthritis Research Therapy 2011 13 R121 http arthritis-research.eom content 13 4 R121 RESEARCH ARTICLE Open Access Successful tumour necrosis factor TNF blocking therapy suppresses oxidative stress and hypoxia-induced mitochondrial mutagenesis in inflammatory arthritis 1 1 1 1 1 2 1 Monika Biniecka Aisling Kennedy Chin T Ng Ting C Chang Emese Balogh Edward Fox Douglas J Veale Ursula Fearon1 and Jacintha N O Sullivan3 Abstract Introduction To examine the effects of tumour necrosis factor TNF blocking therapy on the levels of early mitochondrial genome alterations and oxidative stress. Methods Eighteen inflammatory arthritis patients underwent synovial tissue oxygen tpO2 measurements and clinical assessment of disease activity DAS28-CRP at baseline T0 and three months T3 after starting biologic therapy. Synovial tissue lipid peroxidation 4-HNE T and B cell specific markers and synovial vascular endothelial growth factor VEGF were quantified by immunohistochemistry. Synovial levels of random mitochondrial DNA mtDNA mutations were assessed using Random Mutation Capture RMC assay. Results 4-HNE levels pre post anti TNF-a therapy were inversely correlated with in vivo tpO2 P 0.008 r -0.60 . Biologic therapy responders showed a significantly reduced 4-HNE expression P 0.05 . High 4-HNE expression correlated with high DAS28-CRP P 0.02 r 0.53 tender joint count for 28 joints TJC-28 P 0.03 r 0.49 swollen joint count for 28 joints SJC-28 P 0.03 r 0.50 and visual analogue scale VAS P 0.04 r 0.48 . Strong positive association was found between the number of 4-HNE positive cells and CD4 cells P 0.04 r 0.60 CD8 cells P 0.001 r 0.70 CD20 cells P 0.04 r 0.68 CD68 cells P 0.04 r 0.47 and synovial VEGF expression P 0.01 r 063 . In patients whose in vivo tpO2 levels improved post treatment significant reduction in mtDNA mutations and DAS28-CRP was observed P 0.05 . In contrast in those patients whose tpO2 levels remained the same or reduced at T3 no significant changes