tailieunhanh - Báo cáo y học: "Selective amplification of glucocorticoid anti-inflammatory activity through synergistic multi-target action of a combination drug"

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: Selective amplification of glucocorticoid anti-inflammatory activity through synergistic multi-target action of a combination drug. | Available online http content 11 1 R12 Research article Selective amplification of glucocorticoid anti-inflammatory activity through synergistic multi-target action of a combination drug Grant R Zimmermann William Avery Alyce L Finelli Melissa Farwell Christopher C Fraser and Alexis A Borisy CombinatoRx Incorporated First Street Cambridge MA 02142 USA Corresponding author Grant R Zimmermann gzimmermann@ Received 13 Sep 2008 Revisions requested 5 Nov 2008 Revisions received 1 Dec 2008 Accepted 26 Jan 2009 Published 26 Jan 2009 Arthritis Research Therapy 2009 11 R12 doi ar2602 This article is online at http content 11 1 R1 2 2009 Zimmermann et al. licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Open Access Abstract Introduction Glucocorticoids are a mainstay of antiinflammatory therapy but significant adverse effects ultimately limit their utility. Previous efforts to design glucocorticoid structures with an increased therapeutic window have focused on dissociating anti-inflammatory transcriptional repression from adverse effects primarily driven by transcriptional activation. An alternative to this medicinal chemistry approach is a systems biology based strategy that seeks to amplify selectively the antiinflammatory activity of very low dose glucocorticoid in immune cells without modulating alternative cellular networks that mediate glucocorticoid toxicity. Methods The combination of prednisolone and the antithrombotic drug dipyridamole was profiled using in vitro and in vivo models of anti-inflammatory activity and glucocorticoid-induced adverse effects to demonstrate a dissociated activity profile. Results The combination synergistically suppresses .