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Medicine: Evidence-Based Research: Plenary Session
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Abstract This session will present new evidence-based data from recently performed clinical trails to be chosen before the meeting. (Presentation 23.3) Nitric oxide donors reduce MMP expression in diabetic skin wound fibroblasts J.W. Burrow, J.A. Koch, D.D. Dean, V.L. Sylvia, University of Texas Health Science Center, San Antonio, TX Patients with diabetes are at risk for developing chronic wounds, particularly on the lower extremities where the condition is commonly called the diabetic foot. Chronic foot wounds are a leading cause of hospital admission amongst diabetic patients and are responsible for 50%–70% of all non-traumatic amputations. The non-healing diabetic foot wound displays pathologically elevated matrix metalloproteinase (MMP) activity. In contrast, the concentration of nitric oxide is significantly reduced in chronic ulcers. Our hypothesis is that nitric oxide down regulates MMP expression in diabetic wounds. MMPs, which are important in wound healing include, the collagenases (MMP-1, -8, -13) and gelatinases (MMP-2, -9). In this study we treated diabetic human skin fibroblasts in vitro and diabetic mouse skin wounds in vivo with nitric oxide donor or inhibitor compounds and measured changes in MMP expression. The nitric oxide donors S-nitroso-N-acetylpenicillamine (SNAP), NOR-3 and S-nitrosoglutathione (SNOG) were used and MMP-1, -2, -8, -9, and -13 expression were examined by real-time PCR. We examined the effects of these compounds on wound healing by assessing rate of wound closure between different experimental treatment groups and between control and diabetic mice. The fast-acting nitric oxide donor NOR-3 had no significant effect, but the relatively slower-acting compounds SNAP and SNOG significantly lowered MMP-9 mRNA expression in both control and diabetic fibroblasts. Additionally, SNAP and SNOG accelerated wound healing in diabetic mice to a rate comparable with that of normal mice. The ability to control MMP-induced tissue destruction by regulating nitric oxide production could provide a novel and effective means of promoting wound repair. Supported by Juvenile Diabetes Research Foundation Grant #5-2005-179. References Bohl-Masters KS, et al. Wound Rep Regen. 2002;10:286–294. Mandal M, et al. Mol Cell Biochem. 2003;252:305–329. |
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