Topical Insulin Accelerates Wound Healing in Diabetes by Enhancing the AKT and ERK Pathways: A Double-Blind Placebo-Controlled Clinical Trial

Background: Wound healing is impaired in diabetes mellitus, but the mechanisms involved in this process are virtually unknown. Proteins belonging to the insulin signaling pathway respond to insulin in the skin of rats. Objective: The purpose of this study was to investigate the regulation of the insulin signaling pathway in wound healing and skin repair of normal and diabetic rats, and, in parallel, the effect of a topical insulin cream on wound healing and on the activation of this pathway. Research Design and Methods: We investigated insulin signaling by immunoblotting during wound healing of control and diabetic animals with or without topical insulin. Diabetic patients with ulcers were randomized to receive topical insulin or placebo in a prospective, double-blind and placebo-controlled, randomized clinical trial (NCT 01295177) of wound healing. Results and Conclusions: Expression of IR, IRS-1, IRS-2, SHC, ERK, and AKT are increased in the tissue of healing wounds compared to intact skin, suggesting that the insulin signaling pathway may have an important role in this process. These pathways were attenuated in the wounded skin of diabetic rats, in parallel with an increase in the time of complete wound healing. Upon topical application of insulin cream, the wound healing time of diabetic animals was normalized, followed by a reversal of defective insulin signal transduction. In addition, the treatment also increased expression of other proteins, such as eNOS (also in bone marrow), VEGF, and SDF-1 alpha in wounded skin. In diabetic patients, topical insulin cream markedly improved wound healing, representing an attractive and cost-free method for treating this devastating complication of diabetes.Sao Paulo Research Foundation (FAPESP)Sao Paulo Research Foundation (FAPESP)National Institute of Science and Technology (INCT)National Institute of Science and Technology (INCT)National Council for Scientific and Technological Development (CNPq)National Council for Scientific and Technological Development (CNPq

Platelet-Rich Plasma as an Additional Therapeutic Option for Infected Wounds with Multi-Drug Rresistant Bacteria: In Vitro Antibacterial Activity Study

PURPOSE: Infected wounds, such as diabetic foot infections, are mostly polymicrobial and microorganisms have high resistance rates to antimicrobials. Infected wounds in diabetic patients have high cost, morbidity, and mortality rates. Based on these facts, there is a need for supportive localized treatment options such as platelet-rich plasma (PRP) implementations. Demonstrating the in vitro antimicrobial effect, our aim was to lead up to clinical trials of localized PRP implementations in infected wounds such as diabetic foot infections. In this study, we aimed to demonstrate the in vitro antibacterial activity of PRP against methicilin-resistant Staphylococcus aureus (MRSA) and three more multi-drug resistant bacteria species that are important and hard-to-treat in wound infections. MATERIALS AND METHODS: In vitro antimicrobial activity of autologous PRP, platelet-poor plasma (PPP), and phosphate-buffered saline (PBS) on methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp., extended spectrum beta lactamase producing Klebsiella pneumoniae, and carbapenem-resistant Pseudomonas aeruginosa was compared by assessment of bacterial growth on agar plates and antimicrobial susceptibility test results. RESULTS: When compared to control group, PRP and PPP significantly suppressed bacterial growth of MRSA, K. pneumoniae, and P. aeruginosa at 1st, 2nd, 5th, and 10th hours of incubation (p \u3c 0.05). VRE was the only bacteria that PRP and PPP showed limited activity against. When compared to PPP, PRP showed higher activity against MRSA, K. pneumoniae, and P. aeruginosa. However, the differences between PRP and PPP were statistically significant only against MRSA and P. aeruginosa at the first hour of incubation. CONCLUSIONS: Emerging PRP and other platelet-derived products seem to be promising alternative tools besides antibiotic treatment, debridement, negative pressure wound therapy, hyperbaric oxygen therapy, and other treatment options for treating diabetic foot infections