Effects of calcipotriol on stratum corneum barrier function, hydration and cell renewal in humans

Effendy I, Kwangsukstith C, Chiappe M, Maibach HI. Effects of calcipotriol on stratum corneum barrier function, hydration and cell renewal in humans. British Journal of Dermatology. 1996;135(4):545-549.Calcipotriol, a vitamin D analogue utilized for psoriasis, has irritation as its most frequent reported adverse event, However, studies on its irritant properties in humans have produced conflicting data, This study evaluates the effect of calcipotriol on stratum corneum barrier function, hydration and cell turnover in healthy volunteers, compared with sodium lauryl sulphate (SLS) as a model irritant, Calcipotriol 0.005% ointment and 1% aqueous SLS solution were applied for 60 min once daily for 2 weeks (5 consecutive days weekly) on untreated and on dansyl-chloride-labelled skin. Irritant responses were documented by visual scoring and by measurement of the transepidermal water loss (TEWL) and stratum corneum hydration (electrical capacitance), until day 18. Stratum corneum turnover time (SCTT) was the time in days between staining (day 0) and the disappearance of dansyl fluorescence. SLS caused more erythema, scaling, and a significant TEWL increase for 18 days, In contrast, calcipotriol induced erythema, and slightly but significantly increased TEWL on day 11 only, as compared with the vehicle control (P < 0.05), SLS, but not calcipotriol, caused skin dryness from day 4 to day 18, The shortest SCTT was obtained at SLS-exposed sites (11.2+/-0.7 days: mean +/- SD), Calcipotriol significantly shortened SCTT (16.3 +/- 1.1 days) when compared with its vehicle. Compared with the skin irritation induced by SLS, under these test conditions, calcipotriol is a far weaker irritant on normal human skin, In addition, calcipotriol accelerates stratum corneum turnover to a significantly greater extent than its vehicle

Functional changes in human Stratum corneum induced by topical glycolic acid: Comparison with all-trans retinoic acid

Effendy I, Kwangsukstith C, Lee JY, Maibach HI. Functional changes in human Stratum corneum induced by topical glycolic acid: Comparison with all-trans retinoic acid. Acta Dermato-Venereologica. 1995;75(6):455-458.The effects of topical glycolic acid and all-trans retinoic acid on stratum corneum barrier function and hydration of human skin were investigated in 6 healthy volunteers utilizing non-invasive techniques. In addititon, changes in stratum corneum turnover time induced by the substances were examined using the dansyl chloride fluorescence test. Twelve percent glycolic acid in water and 0.1% retinoic acid in ethanol, respectively, were applied for 60 min once daily, over a period of 2 weeks (5 consecutive days weekly) on dansyl chloride-labelled skin and on untreated skin. During a 10-day application period, both glycolic acid and retinoic acid similarly induced a significant increase in TEWL. However, after discontinuing treatment, TEWL in retinoic acid-exposed skin remained increased, Glycolic acid significantly reduced stratum corneum hydration from day 11 to day 18 (p<0.05), while retinoic acid induced skin dryness after 9 days of treatment, which persisted until day 18 (p<0.005). Whereas glycolic acid rapidly induced an intense erythema implying a direct non-specific inflammatory response, the retinoic acid exposed skin gradually developed erythema. Retinoic acid caused scaling to a greater extent than did glycolic acid, even after treatment cessation. Both glycolic acid and retinoic acid significantly decreased stratum corneum turnover time and stratum cor neum turnover time(50) (the time in days from labelling until approximately 50% of fluorescence disappeared), compared with the vehicle controls. However, glycolic acid shortened stratum corneum turnover time (12.8 +/- 0.9 days) as well as stratum corneum turnover time(50) (7.3 +/- 0.7 d) significantly more than did retinoic acid (15.8 +/- 0.7 d and 9 +/- 0.8 d, respectively). While ethanol (vehicle of retinoic acid) slightly but significantly decreased stratum corneum turnover time (p<0.05), water (vehicle of glycolic acid) did not. This study showed that both glycolic acid and retinoic acid induced certain functional changes in stratum cor neum, mirroring their irritation potential. However, changes at retinoic acid exposed sites appeared longer-lasting, implying a distinct mode of action. An increase in stratum corneum turnover induced by the substances may be, in part, linked with their irritation properties

Effects of all-trans retinoic acid and sodium lauryl sulphate on the permeability of human skin in vitro

Effendy I, Weltfriend S, Kwangsukstith C, Singh P, Maibach H. Effects of all-trans retinoic acid and sodium lauryl sulphate on the permeability of human skin in vitro. British Journal of Dermatology. 1996;135(3):428-432.Recent in vivo investigations have shown that pretreatment with topical all-trans retinoic acid (RA) may diminish the skin response to sodium lauryl sulphate (SLS), This study evaluated the permeation of SLS through human skin after pretreatment with RA, and vice versa, by in vitro methods, The permeability coefficient of SLS (3.24 +/- 0.21 x 10(3) cm/h) and the 24-h cumulative amount of SLS 3.41 +/- 0.6% of dose applied) permeating RA-pretreated skin did not differ significantly from those across untreated skin (control) (P > 0.05). In contrast, the permeability coefficient of RA (0.23 +/- 0.05 x 10(3) cm/h) and its 24-h cumulative amount (0.37 +/- 0.05% of dose applied) penetrating SLS-pretreated skin were significantly greater than these permeating untreated skin (P < 0.05). Thus, an increase in RA penetration was induced by SLS pretreatment; however, pretreating the skin with RA did not inhibit the percutaneous permeation of SLS. Based on previous in vivo findings where RA reduced skin reactions to SLS,(8) one would speculate that RA pretreatment may decrease SLS penetration. However, these penetration data do not necessarily uphold this presumption. Perhaps, other interactions between the substances and the skin, e,g, at cellular levels, may be responsible for the differing skin responses