Validation of an in vivo wound healing model for the quantification of pharmacological effects on epidermal regeneration.

BACKGROUND: Non-invasive assessment methods such as measurement of the transepidermal water loss (TEWL) allow a continuous follow-up of cutaneous processes with impairment of the epidermal barrier function. OBJECTIVE: The aim of the trial was to establish an in vivo model for the assessment of drug effects on epidermal regeneration. METHODS: Twenty healthy volunteers were included in this double-blind randomized trial. After setting four suction blisters on the volar aspect of the forearm, the epidermis was removed to create a standardized subepidermal wound. Thereafter the wounds were treated topically for 6 h daily during 14 days. The following treatments were to be compared: a clobetasol 17-propionate preparation under occlusion, a corticoid-free cream under occlusion, no treatment and occlusion (aluminium chamber), no treatment and no occlusion. Daily measurement of TEWL above the wounds was performed. RESULTS: The 0.05% clobetasol 17-propionate preparation caused a dramatic delay in TEWL decrease, whereby the untreated unoccluded field showed a continuous decrease over the observed period of 14 days. Occlusion and corticoid-free treatment led to a weak but significant delay of TEWL decrease when compared to the untreated unoccluded test field. CONCLUSION: This model seems to describe re-epithelialization in a reliable manner and can be used for in vivo assessment of drug effects on migrating and proliferating epithelial cells.

Comparison of the effects of calcipotriol, prednicarbate and clobetasol 17-propionate on normal skin assessed by ultrasound measurement of skin thickness.

In this study, we investigated the effect of calcipotriol, prednicarbate and clobetasol 17-propionate on skin thickness over a treatment period of 6 weeks. The study was conducted as a controlled, randomized, double-blind comparison. The influence of these drugs on normal skin under occlusive conditions was assessed visually and by measuring skin thickness using 20 MHz B mode ultrasound. Both topically applied glucocorticosteroids lead to a significant decrease in skin thickness. In contrast to the glucocorticosteroid-induced atrophy, calcipotriol application on normal skin leads to an increase in skin thickness in all volunteers. The effect remains constant for the duration of treatment. The cause of this increase seems to be an irritative reaction of the skin which was histologically investigated in one volunteer. The histological features of this reaction are characteristic for a subacute dermatitis. The implications of these findings for the therapeutic mechanism of calcipotriol are discussed.

[Imaging subcutaneous atrophy in circumscribed scleroderma with 20 MHz B-scan ultrasound]. / Darstellung der subkutanen Atrophie bei der zirkumskripten Sklerodermie im 20-MHz-B-scan Ultraschall.

The technique of 20-MHz B-scan sonography is non-invasive and allows quantification of the different compartments of the skin. Seven patients with atrophic linear circumscribed scleroderma and one patient with guttate circumscribed scleroderma were examined by ultrasound. All patients were found to have a total or subtotal loss of subcutaneous fatty tissue, whereas the thickness of the dermis remained almost unchanged. These findings should lead to further investigation of the pathophysiological mechanism involved in subcutaneous atrophy in circumscribed scleroderma.

Effects of azelaic acid on sebaceous gland, sebum excretion rate and keratinization pattern in human skin. An in vivo and in vitro study.

The effects of azelaic acid (AZA) on the epidermis of 47 individuals (12 with normal skin, 15 with seborrheic skin and 20 suffering from acne) and on in vitro cultured keratinocytes are reported. Topical application of a 20% AZA cream significantly improved the lesions of acne patients, but failed to induce clinically detectable changes in normal or seborrheic epidermis. Complementary investigations clearly showed that AZA treatment failed to induce specific changes in sebum composition, excretion rate, or in the size of sebaceous glands, but modified epidermal keratinization. Keratohyalin granules and tonofilament bundles were reduced in size and number, mitochondria were swollen and the rough endoplasmic reticulum of malpighian keratinocytes enlarged. The infundibular epidermis of acne individuals showed marked reduction of the horny layer thickness, widening of the horny cell cytoplasm, transitional corneal cells, normalization of filaggrin distribution, and the comedo contained few bacteria and spores. In vitro, AZA exerted marked time- and dose-dependent antiproliferative cytostatic effects on cultured keratinocytes, with a 50% inhibitory dose of 20 mM, decreased some keratinocyte proteins (highly soluble fractions S2, keratohyalin macroaggregate R2, and non-cross-linked fibrous protein S4) and a 95 kD and a 35 kD protein of the cytosolic fraction. Mitochondria were frequently damaged and the rough endoplasmic reticulum enlarged. Our results indicate that AZA is an antikeratinizing agent, displaying antiproliferative cytostatic effects on keratinocytes and modulating the early and terminal phases of epidermal differentiation.