(from the application): The long term objective of this research is to determine if Simulium vittatum erythema protein (SVEP), a potent vasodilator protein that evolved in insect saliva to increase blood flow in skin, can be used therapeutically in human diseases associated with inadequate skin blood perfusion. The specific objectives of this proposed pilot project are to elucidate the specific cellular binding site of SVEP in skin, to test its mechanism of action, and to assess its efficacy for increasing the rate and/or strength of surgically-induced wound healing. In vivo injected rSVEP, will be localized in skin punch biopsies by immunohistochemical staining. Glyburide, a specific inhibitor of ATP dependent potassium channels (K+ATP), will be co-injected with increasing concentrations of rSVEP to evaluate the presence and level of inhibition of perfusion. Intralesional injections of rSVEP in both open and closed wounds, administered intradermally or subcutaneously will be used to test the hypothesis that increased blood perfusion induced by rSVEP improves wound repair. The outcome will be determined using objective, quantitative measures of perfusion and wound recovery. These data will consist of 1) scanning laser Doppler imaging for quantitative changes in skin perfusion, 2) tensiometry for wound strength of closed wounds, 3) planimetry for rates of contraction, epithelialization, and total healing of open wounds, 4) histopathology for assessing the inflammatory and repair stages of healing, 5) immunohistochemistry to detect angiogenesis. The data from this pilot study will provide the foundation for further elucidation of the pharmacology of SVEP action and for investigating the effects of vasodilatory therapy on such problematic wounds as decubital ulcers, diabetic foot ulcers and severely traumatized wounds.
