Development of novel GI-centric prostaglandin E receptor type 4 (EP4) agonist prodrugs as treatment for ulcerative colitis and other intestinal inflammatory diseases.

Prostaglandin E receptor type 4 (EP4) agonists have been shown to be effective in treating experimental ulcerative colitis (UC) in animals and in human clinical trials, but their development has been impeded by unacceptable systemic side effects. In this study, a series of methylene phosphate prodrugs of a highly potent and selective prostaglandin EP4 receptor agonist were designed to target and remain localized in the gastrointestinal (GI) tract after either oral or rectal instillation. The prodrugs were designed to be converted to liberate active EP4 agonist by intestinal alkaline phosphate (IAP), a ubiquitous enzyme found at the luminal of the intestinal wall thus exposing the colon epithelial barrier while reducing systemic exposure to the active agonist.

Bolstering connectedness through peer support: Randomized-controlled trial of a web-based peer support program for adolescents with inflammatory bowel disease.

Background: Inflammatory bowel disease (IBD) is a chronic autoimmune disease often diagnosed during adolescence. IBD negatively impacts all aspects of health-related quality of life, resulting in physical, emotional, social, school, and work functioning challenges. Adolescents have identified the need for peer support in managing their disease and promoting positive health outcomes.

A2B adenosine receptor-triggered intracellular calcium mobilization: Cell type-dependent involvement of Gi, Gq, Gs proteins and protein kinase C.

Activation of PLCβ enzymes by G and G proteins is a common mechanism to trigger cytosolic Ca increase. We and others reported that G inhibitor FR900358 (FR) can inhibit both and G- and, surprisingly, G-mediated intracellular Ca mobilization. Thus, the G-G-PLCβ-Ca signaling axis depends entirely on the presence of active G, which reasonably explained FR-inhibited G-induced Ca release.

Pregnancy and age differentially affect stiffness, injury susceptibility, and composition of murine uterosacral ligaments.

Pelvic organ prolapse is a debilitating condition that diminishes quality of life, and it has been linked to pregnancy and aging. Injury of the uterosacral ligaments (USLs), which provide apical support to the pelvic organs, is a major cause of uterine prolapse. In this study, we examined the effect of pregnancy and age on the apparent elastic modulus, susceptibility to collagen damage, and extracellular matrix (ECM) composition of the murine USL.