Phase II clinical trials have reported that acute treatment of surgical skin wounds with the therapeutic peptide alpha Connexin Carboxy-Terminus 1 (αCT1) improves cutaneous scar appearance by 47% 9-month postsurgery. While Cx43 and ZO-1 have been identified as molecular targets of αCT1, the mode-of-action of the peptide in scar mitigation at cellular and tissue levels remains to be further characterized. Scar histoarchitecture in αCT1 and vehicle-control treated skin wounds within the same patient were compared using biopsies from a Phase I clinical trial at 29-day postwounding. The sole effect on scar structure of a range of epidermal and dermal variables examined was that αCT1-treated scars had less alignment of collagen fibers relative to control wounds-a characteristic that resembles unwounded skin. The with-in subject effect of αCT1 on scar collagen order observed in Phase I testing in humans was recapitulated in Sprague-Dawley rats and the IAF hairless guinea pig. Transient increase in histologic collagen density in response to αCT1 was also observed in both animal models. Mouse NIH 3T3 fibroblasts and primary human dermal fibroblasts treated with αCT1 in vitro showed more rapid closure in scratch wound assays, with individual cells showing decreased directionality in movement. of 19 |MONTGOMERY ET al. | METHODS | Peptide sequencesαCT1 peptide corresponds to a short sequence at the Cx43 CT linked to an antennapedia internalization sequence (RQPKIWFPNRRKPWKKRPRPDDLEI) as first described An agent-based computational model parameterized with fibroblast motility data predicted collagen alignments in simulated scars consistent with that observed experimentally in human and the animal models. In conclusion, αCT1 prompts decreased directionality of fibroblast movement and the generation of a 3D collagen matrix postwounding that is similar to unwounded skin-changes that correlate with longterm improvement in scar appearance.
Background Multimodal perioperative pain-management protocols have contributed to the success of elective total joint replacement in orthopedic surgery. General or neuraxial anesthesia for arthroplasty is accompanied by complications such as pruritis, nausea, and vomiting. Dexamethasone has been demonstrated to be a safe perioperative antiemetic. This study evaluates the benefit of low-dose intravenous dexamethasone used in the perioperative period to prevent postoperative nausea and vomiting. Methods Two scheduled doses of 8 mg of dexamethasone 12 hours apart after total hip arthroplasty or total knee arthroplasty were given to a dexamethasone group (n = 492) and were retrospectively compared with a no-dexamethasone group (n = 364) based on the use of antiemetics in the postoperative period. Frequency of antiemetic use in both groups was compared using a zero-inflated fixed-model Poisson distribution. Additional analysis included need for opioid analgesic, administration of diphenhydramine, and postoperative infection rates at 30 and 90 days. Results The dexamethasone group was found to have a significant reduction in need for the rescue antiemetic ondansetron ( P = .00194). There was an associated reduction in length of stay for the treatment group (mean 1.83 days) relative to the control group (mean 2.17 days) ( P < .001). There was no significant difference in postoperative infection rates at 30 or 90 days after arthroplasty. Conclusions Dexamethasone is a safe adjunct to perioperative protocol that may reduce nausea, thus improving patient satisfaction. There is an associated reduction in length of stay that may reduce cost of hospitalization.
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