Assessment of wound healing efficacy and tolerability using CicatrylTM cream based on a suction blister model in healthy subjects

Background: CicatrylTM cream, a topical medical device, is indicated for the treatment of superficial wounds and small skin injuries. Objectives: To assess the efficacy and tolerability of CicatrylTM cream by measuring the recovery of the skin barrier after inducing wounds. Materials & Methods: A suction blister of about 6-mm diameter was induced on the inner side of each forearm of 44 healthy subjects. Using a process of randomisation, CicatrylTM cream was then applied to one wound for a maximum duration of 14 days, while the other wound was left untreated. The primary objective was to evaluate the effect of the test product on wound healing at Day 6, by comparing treated versus untreated wound areas measured by macrophotography. Secondary objectives were to evaluate healing, cutaneous barrier restoration and subjective efficacy of the cream as well as tolerability. Results: The mean wound area (± SD) at Day 6 was significantly smaller for treated wounds compared with untreated wounds (1.76±4.71 vs 15.76±7.61 mm2; p < 0.0001). For treated wounds, wound healing between Days 1 and 6 was 1.6-fold faster compared with untreated wounds (-7.90 vs-4.79 mm2/day; p < 0.0001), and the wounds healed in approximately half the time (6.8 vs 12.2 days for untreated wounds). Cutaneous barrier restoration occurred earlier for treated wounds (Day 6 vs Day 8 for untreated wounds). The cream was well tolerated, and no serious adverse events were observed. Conclusion: CicatrylTM cream improves wound healing, especially within the first six days, if applied in accordance with the manufacturer's instructions.

Cav1.4 calcium channels control cytokine production by human peripheral TH17 cells and psoriatic skin-infiltrating T cells.

BACKGROUND: Type-17 inflammation characterizes psoriasis, a chronic skin disease. Because several inflammatory cytokines contribute to psoriasis pathogenesis, inhibiting the simultaneous production of these cytokines in TH17 cells may be beneficial in psoriasis. We found that Cav1.4, encoded by CACNA1F, was the only Cav1 calcium channel expressed in TH17 cells. OBJECTIVE: We sought to investigate the role of Cav1.4 expression in early TH17-activation events and effector functions, as well as its association with TH17 signature genes in lesional psoriatic (LP) skins. METHODS: Transcriptional gene signatures associated with CACNA1F expression were examined in LP skins by RT-PCR and in situ hybridization. Cav1 inhibitor and/or shRNA lentivectors were used to assess the contribution of Cav1.4 in TH17 activation and effector functions in a 3-dimensional skin reconstruction model. RESULTS: CACNA1F expression correlated with inflammatory cytokine expression that characterizes LP skins and was preferentially associated with RORC expression in CD4+ and CD4- cells from LP biopsies. Nicardipine, a Cav1 channel antagonist, markedly reduced inflammatory cytokine production by TH17 cells from blood or LP skin. This was associated with decreased TCR-induced early calcium events at cell membrane and proximal signaling events. The knockdown of Cav1.4 in TH17 cells impaired cytokine production. Finally, Cav1 inhibition reduced the expression of the keratinocyte genes characteristic of TH17-mediated psoriasis inflammation in human skin equivalents. CONCLUSIONS: Cav1.4 channels promote TH17-cell functions both at the periphery and in inflammatory psoriatic skin.