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- Gronberg, Alvar, et al.
(författare)
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Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers : a randomized, placebo-controlled clinical trial
- 2014
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Ingår i: Wound Repair and Regeneration. - : Wiley. - 1067-1927 .- 1524-475X. ; 22:5, s. 613-621
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Tidskriftsartikel (refereegranskat)abstract
- Venous leg ulcers (VLUs) are one of the most prevalent types of chronic wounds. The aim of this study was to determine the safety and dose-response efficacy of the human synthetic peptide LL-37 in the treatment of hard-to-heal VLUs. This first-in-man trial included 34 participants with VLUs and comprised a 3-week, open-label, run-in period on placebo, followed by a 4-week randomized double-blind treatment phase with twice weekly applications of LL-37 (0.5, 1.6, or 3.2 mg/mL) or placebo, and a 4-week follow-up. The healing rate constants for 0.5 and 1.6 mg/mL of LL-37 were approximately six-and threefold higher than for placebo (p = 0.003 for 0.5 mg/mL and p = 0.088 for 1.6 mg/mL). Square-root transformed wound area data showed improved healing for the 0.5 and 1.6 mg/mL dose groups compared with pretreatment values (p < 0.001 and p = 0.011, respectively). Consistently, treatment with the two lower doses markedly decreased the mean ulcer area (68% for 0.5 mg/mL and 50% for 1.6 mg/mL groups). No difference in healing was observed between the groups receiving 3.2 mg/mL of LL-37 and placebo. There were no safety concerns regarding local or systemic adverse events. In conclusion, topical treatment with LL-37 for chronic leg ulcers was safe and well tolerated with the marked effect on healing predictors at the two lower doses warranting further investigations.
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- Koskela, Anita, 1979-, et al.
(författare)
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Regulation of fibroblast gene expression by keratinocytes in organotypic skin culture provides possible mechanisms for the antifibrotic effect of reepithelialization
- 2010
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Ingår i: Wound Repair and Regeneration. - : The Wound Healing Society. - 1067-1927 .- 1524-475X. ; 18:5, s. 452-459
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the mechanisms behind the antifibrotic effect associated with epidermal regeneration, the expression of 12 fibroblast genes important for the modulation of the extracellular matrix (ECM), as well as alpha-smooth muscle actin, was studied in a keratinocyte-fibroblast organotypic skin culture model. The study was performed over time during epidermal generation and in the presence or absence of the profibrotic factor transforming growth factor-beta. the Presence of epidermal differentiation markers in the model was essentially coherent with that of native skin. Fibroblast gene expression was analyzed with real-time polymerase chain reaction after removal of the epidermal layer. After 2 days of air-exposed culture, 11 out of the 13 genes studied were significantly regulated by keratinocytes in the absence or presence of transforming growth factor-beta. The regulation of connective tissue growth factor, collagen I and III, fibronectin, plasmin system regulators, matrix metalloproteinases and their inhibitors as well as alpha-smooth muscle actin was consistent with a suppression of ECM formation or contraction. Overall, the results support a view that keratinocytes regulate fibroblasts to act catabolically on the ECM in epithelialization processes. This provides possible mechanisms for the clinical observations that reepithelialization and epidermal wound coverage counteract excessive scar formation.
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