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Báo cáo y học: "Comparative efficacy of a secretory phospholipase A2 inhibitor with conventional anti-inflammatory agents in a rat model of antigen-induced 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: Comparative efficacy of a secretory phospholipase A2 inhibitor with conventional anti-inflammatory agents in a rat model of antigen-induced arthritis | Coulthard et al. Arthritis Research Therapy 2011 13 R42 http arthritis-research.eom content 13 2 R42 RESEARCH ARTICLE Open Access Comparative efficacy of a secretory phospholipase A2 inhibitor with conventional anti-inflammatory agents in a rat model of antigen-induced arthritis Liam G Coulthard Jaclyn Costello Brent Robinson Ian A Shiels Stephen M Taylor and Trent M Woodruff Abstract Introduction Previously secretory phospholipase A2 sPLA2 inhibition has been used as an adjunct to conventional rheumatoid arthritis therapy in human clinical trials without significant improvement of arthritic pathology. In this study we compared the efficacy of a potent and orally active group IIa secretory phospholipase A2 inhibitor sPLA2I to conventional anti-arthritic agents infliximab leflunomide and prednisolone in a rat model of antigen-induced arthritis. Methods Initially to establish efficacy and dose-response rats were orally dosed with the sPLA2I 1 and 5 mg kg two days prior to arthritis induction and then daily throughout the 14-day study period. In the second trial rats were orally dosed with the sPLA2I 5 and 10 mg kg day beginning two days after the induction of arthritis at the peak of joint swelling. Separate groups of rats were also dosed with the tumour necrosis factor-alpha TNF-a inhibitor infliximab single 3 mg kg i.v. injection leflunomide 10 mg kg day oral or prednisolone 1 mg kg day oral at this same time point and used as comparative treatments. Results In the pathology prevention trial both 1 and 5 mg kg dose groups of sPLA2I demonstrated a significant reduction in joint swelling and gait disturbances however only the higher 5 mg kg dose resulted in significantly reduced histopathology scores. In the post-induction trial rats dosed with sPLA2I showed a significant improvement in joint swelling and gait scoring whereas none of the conventional therapeutics achieved a significant decrease in both of these two disease markers. Histopathological scoring at the .