Chitosan dressing promotes healing in third degree burns in mice: gene expression analysis shows biphasic effects for rapid tissue regeneration and decreased fibrotic signaling.

Burns are a significant health challenge and healing can result in scar formation. Chitosan, a derivative of chitin, has been used to promote wound healing. In this study we used gene expression profiling in a mouse model of full thickness cutaneous burn to assess the benefits of treating with a chitosan lactate dressing. Three days after wounding mice treated with chitosan showed increased expression of genes associated with formation of granulation tissue. At a later time point, seven days after wounding, genes that initially showed increased expression were now down-regulated, and there was increased expression of genes involved in remodeling suggesting that the chitosan treatment results in accelerated healing. Quantitative RT-PCR showed modulated mRNA levels for TGFß1 by the chitosan dressing. TGFß1 initially promotes healing but extended activity can result in scarring. Importantly we found that expression was elevated at day three, but decreased at day seven suggesting that chitosan treatment will not result in scar formation, and may even be beneficial in preventing scar formation. Additionally, the biphasic regulation of expression of TGFß1 could be a powerful biomarker for future studies of the wound-healing potential of chitosan based and other treatments for burn wounds.

The addition of sirolimus to cyclosporine and steroids inhibits the anti-equine antibody response in renal transplant recipients treated with antithymocyte globulin.

Polyclonal antibodies, such as equine antithymocyte globulin (ATGAM), are known to induce antibody formation. This study evaluated the in vivo effect of sirolimus on antibody formation associated with the use of equine antithymocyte globulin in renal transplant recipients. Recipients of either a living-related donor or cadaveric renal allograft received azathioprine (AZA) (n = 15), mycophenolate mofetil (MMF) (n = 12), or sirolimus (n = 15) in addition to baseline immunosuppression with corticosteroids, cyclosporine, and equine antithymocyte globulin. Immediately before transplantation and weekly for at least 1 month, sequential serum specimens were tested for the presence of human anti-equine antibody using an enzyme-linked immunosorbent assay (ELISA). Anti-equine antibody formation was significantly different among the three treatment groups. Fewer patients receiving MMF (17%, p = 0.007 vs. AZA) and sirolimus (13%, p = 0.003 vs. AZA) developed anti-equine antibody compared with AZA (66%). There was no significant difference (p = 0.81) in the sensitization to equine antithymocyte globulin when comparing the patients receiving MMF or sirolimus. In the sensitized patients, high anti-equine antibody titers (>1 : 500) were more common in those receiving AZA (n = 3) than MMF (n = 0) or sirolimus (n = 1). Compared to AZA, sirolimus, when given in combination with cyclosporine A, significantly reduced anti-equine antibody formation to a degree similar to MMF.