This resubmission with substantially sharpened goals and experimental design based on considerable new preliminary data now fully addresses the reviewers' questions. Building on promising preliminary data, we shall define the dose effects of alanyl-glutamine relative to glutamine, glucose, and other glutamine derivatives (including acetyl-glutamine) both in vitro and in vivo. Specifically, in vitro studies will examine intestinal epithelial repair, differentiation and prevention of apoptosis. In vivo studies will examine cyclic AMP and cyclic GMP-mediated secretory diarrhea induced by the toxins of V. cholerae and ST of E. coli, respectively, and the inflammatory, destructive enteritis induced by C. difficile toxin A or cytotoxic chemotherapy. Our overall goal for this first year is to have essential in vitro and in vivo data to support pilot human studies of alanyl-glutamine's effectiveness. Success will open commercial development of an effective new ORNT product for enhancing intestinal repair and absorptive function that could have relevance across a diverse range of human and animal applications.
NOT AVAILABLE
| Carneiro, Benedito A; Fujii, Jun; Brito, Gerly A C et al. (2006) Caspase and bid involvement in Clostridium difficile toxin A-induced apoptosis and modulation of toxin A effects by glutamine and alanyl-glutamine in vivo and in vitro. Infect Immun 74:81-7 |
| Brito, Gerly A C; Carneiro-Filho, Benedito; Oria, Reinaldo B et al. (2005) Clostridium difficile toxin A induces intestinal epithelial cell apoptosis and damage: role of Gln and Ala-Gln in toxin A effects. Dig Dis Sci 50:1271-8 |
| Carneiro-Filho, Benedito A; Oria, Reinaldo B; Wood Rea, Katie et al. (2004) Alanyl-glutamine hastens morphologic recovery from 5-fluorouracil-induced mucositis in mice. Nutrition 20:934-41 |
