Human keratinocyte growth factor-2 (KGF-2) is a member of the fibroblast growth factor family that promotes healing of experimental small intestinal ulceration and colitis. The aim of this study was to determine whether repifermin, a truncated form of recombinant human KGF-2, reverses abnormalities in colonic mucosal transport in a murine model of dextran sulfate sodium (DSS)-induced colitis. Male Swiss-Webster mice were given 4% DSS in drinking water for 7 days and then normal drinking water for 3 days. Repifermin (5 mg kg(-1), i.p.) or vehicle was administered daily for 7 days starting on Day 4 of DSS exposure. On Day 10, net ion transport was measured electrophysiologically in colonic mucosal sheets. Repifermin significantly reduced DSS-induced colonic inflammation measured by tissue myeloperoxidase activity. Concurrently, in colonic tissue taken from mice treated with repifermin, there was a normalization of basal potential difference and short circuit current, and an improvement in the secretory responses to stimulation of muscarinic and ganglionic cholinoceptors. In control mice, repifermin did not interact directly with colonic epithelial cells or intramural neurones to induce immediate changes in net electrogenic transport. The results suggest that repifermin therapy may improve the mucosal electrogenic transport that is impaired during colitis.
Delivering effective drugs at sufficiently high concentrations to the area of infection is a standard treatment for infectious disease, such as endophthalmitis. This is currently done by empirical trans pars plana intravitreal injection of both antibiotics directed against gram-positive and gram-negative microorganisms and steroids. However, injections by needles repeatedly may increase the risks of intraocular infection and hemorrhage, as well as retinal detachment. This article explores the alternative of using biodegradable polymers as scleral plugs for a long-term drug release in vivo. To manufacture plugs, poly(lactide-glycolide) copolymers were first mixed with vancomycin, amikacin, and dexamethasone. The mixture was compressed and sintered at 55 degrees C to form scleral plugs 1.4 mm in diameter. Biodegradable scleral plugs released high concentrations of antibiotics (well above the minimum inhibitory concentrations, MIC) and steroids in vivo for the period of time needed to treat intraocular infection. In addition, no major complications such as infectious or sterile endophthalmitis, retinal detachment, ocular phthisis, or uvea protrusion at sclerotomy site were observed throughout the experiment. The sclerotomy wound healed after total degradation of the scleral implants without leakage or local necrosis. Antibiotic/steroid-impregnated biodegradable scleral plugs may have a potential role in the treatment of various intraocular infections.
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