Topical S-nitrosoglutathione-releasing hydrogel improves healing of rat ischaemic wounds.

Topical application of the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) is known to exert beneficial effects on wound healing. The aim of this study was to evaluate, for the first time, the effect of topical application of GSNO on the healing of ischaemic wounds. Wistar rats were submitted to two parallels incisions on their backs; the skin was separated from the underlying tissue, the incisions were sutured and an excisional wound was made between the parallel incisions to create an ischaemic condition surrounding the wound. The animals were separated into a control group, which received a hydrogel vehicle without GSNO, and a GSNO-treated group, which received a GSNO-containing hydrogel. The animals were treated for 7 days consecutively with one daily application. The GSNO-treated group displayed higher rates of wound contraction and re-epithelization, lower amounts of inflammatory cells, an increase in collagen fibre density and organization and a decrease in the neovascularization compared to control. These results show that topical application of GSNO is effective in the treatment of ischaemic wounds, leading to a significant improvement in the wound healing. Therefore, topical GSNO-containing hydrogels have potential for the therapeutic treatment of ischaemic diabetic and venous ulcers.

The role of indoleamine 2, 3-dioxygenase in lepromatous leprosy immunosuppression.

To elucidate further the possible role of the tryptophan, rate-limiting enzyme indoleamine 2, 3-dioxygenase (IDO) in leprosy, the distribution of IDO-positive cells and IDO activity in the skin biopsies and sera of these patients representing the entire spectrum of the disease were studied. An increased number of macrophages/dendritic cells (DC-lineage IDO(+) cells were found in lepromatous (LL) compared to tuberculoid (BT) and reversal reaction (RR) patients. IDO-positive cells showing CD68 and CD86 surface markers predominated in LL lesions, while higher levels of IDO activity were observed in the sera of LL versus BT patients. Tests revealed an increased IDO message in Mycobacterium leprae-stimulated peripheral blood mononuclear cells (PBMC) by real-time polymerase chain reaction (PCR) and increased IDO expression in M. leprae-stimulated CD14(+) cells of both healthy controls (HC) and LL patients, as evaluated via flow cytometry. Increased M. leprae-induced IDO-protein synthesis was also confirmed by Western blot. Based on our in vitro studies, it was confirmed that M. leprae up-regulated IDO expression and activity in HC and LL monocytes. Interferon (IFN)-γ synergized with M. leprae in promoting IDO expression and activity in monocytes. IDO expression induced by both IFN-γ and M. leprae was abrogated by 1-methyltryptophan (1-MT). Our data suggest that M. leprae chronic infection activates the suppressive molecule IDO which, in turn, contributes to the specific immunosuppression observed in LL leprosy.