The findings of this study support the use of TVR twice daily regardless of fibrosis stage or IL28B genotype, thus offering the potential of simplified TVR dosing to G1 HCV-infected patients, including those with advanced fibrosis or cirrhosis. The authors thank the patients and investigators who participated in the phase 3 study for their participation and support; the members of the Janssen telaprevir team (in particular, J. Mrus, E. O’Neil, I. Dierynck, A. Ghys, and Y. Wyckmans) for their input; and the members of the data and safety monitoring board: chairperson
Francesco Negro, MD; Dominique Larrey, MD; Tim Friede, PhD; and Christian Funck-Brentano, MD, PhD. Writing Idelalisib assistance was provided by Sally Gray (Gardiner-Caldwell Communications, Macclesfield, England) and funded by Janssen Pharmaceuticals. “
“The mammalian gastrointestinal tract harbors a dense and diverse community of an estimated 10−100 trillion micro-organisms1, 2 and 3 consisting of 500−1000 different
species, of which the vast majority are bacteria.2 and 4 It is well accepted that in inflammatory bowel disease (IBD), the mucosal immune system reacts inappropriately toward the commensal microbiota.5 No particular microbial species has been consistently linked to IBD pathogenesis or prevention; however, some symbiotic bacterial species have been shown HSP targets to prevent inflammatory host responses.2, 6, 7, 8 and 9
Numerous animal models have been generated to experimentally investigate human IBD,10 including erosive models of acute colitis (eg, dextran sodium sulfate [DSS]-induced colitis), spontaneous models of chronic colonic, and/or small bowel inflammation induced by targeted gene deletion (eg, interleukin [IL]10−/− mice) or induction by disruption of T-cell homeostasis (eg, Rag1−/− mice). 10 As chronic colitis results from a dysregulated immune response to components of the normal intestinal Gefitinib manufacturer microbiota, it is reasonable to suggest that the T-cell−dependent models are significantly more relevant to human disease than are the erosive models of acute colitis, if one wishes to investigate the immunologic mechanisms inducing, perpetuating, or preventing chronic colitis. 10 Microbe-associated molecular pattern, such as lipopolysaccharide (LPS) or flagellins, are recognized by different pattern recognition receptors. However, there is a dichotomic role for Toll-like receptor (TLR) in intestinal inflammation. 11 For example, IL2−/−MyD88−/− mice develop colitis independent of TLR signaling, and IL10−/−MyD88−/− mice remain healthy, indicating an inflammation promoting effect of MyD88-dependent TLR.