Dynamics of skin barrier repair following topical applications of miconazole nitrate.

The skin barrier function (SBF) is an important aspect of skin biology, particularly in the elicitation of inflammation. The SBF recovery rate after tape stripping and surfactant challenge can be assessed by measuring the transepidermal water loss (TEWL). Previous clinical studies have shown some inflammatory effect after topical applications of miconazole. The aim of this study was to compare the effect of pastes (petrolatum and 15% zinc oxide) containing or not miconazole nitrate on controlled impaired SBF. Fifteen volunteers were enrolled. In each subject, successive cyanoacrylate skin surface strippings were harvested from 5 sites of the volar forearm until TEWL raised above 15 g/cm(2)/h on all test sites. In addition, one daily soak session with a 0.2% dishwashing liquid further damaged the SBF. Each of the test formulations was applied twice daily for 5 days at two dosages, namely 1 and 2 mg/cm(2), on randomized test sites. Another site remained untreated. TEWL was measured daily for 5 days. A fastened SBF repair was observed on all treated sites, particularly where the largest amount of the products had been applied. A faster SBF recovery rate was obtained at the site receiving the miconazole nitrate paste. We conclude that the occlusive effect of a paste helped mitigate SBF defect. The adjunction of miconazole nitrate improved the efficacy.

Healing effect of ketanserin on chronic leg ulcers in patients with diabetes.

BACKGROUND: The treatment of chronic leg ulcers remains a stubborn problem in many patients. Topical 2% ketanserin ointment, a 5HT2-serotoninergic blocking agent, has been reported to improve healing of decubitus, venous, diabetic and ischaemic ulcers. METHOD: The present double-blind intra-individual comparative study was performed in 12 women with diabetes presenting with at least two similar leg ulcers. In each subject, the two lesions were randomly assigned to be treated for 8 weeks by 2% ketanserin ointment or its unmedicated vehicle. OBJECTIVE: assessments of the dynamics of wound healing were performed using computerized morphometry. Evaluations were performed at 2-week intervals for 8 weeks. RESULTS: A significant decrease in relative wound area was observed on the ketanserin-treated ulcers compared with the placebo group. CONCLUSION: Topical ketanserin is a valuable therapy for difficult-to-treat leg ulcers.

Activity of the triazole antifungal r126638 as assessed by corneofungimetry.

BACKGROUND: R126638 is a novel triazole exhibiting potent in vitro and in vivo antifungal activity against fungal pathogens including dermatophytes and yeasts. OBJECTIVE: To determine the antifungal activity in time in the stratum corneum of healthy volunteers after oral intake of R126638 at a daily dose of 100 or 200 mg for 1 week. METHOD: Sixteen male volunteers were randomly allocated to oral treatment with either 100 or 200 mg of R126638 once daily for 1 week. Five cyanoacrylate skin surface strippings (CSSS) were obtained from the forearm of each subject before drug intake at day 1. CSSS were also collected during treatment at day 2 (24 h after the first drug intake, before the second drug intake), at day 4 (before the fourth drug intake) and at day 7 (10 h after the last drug intake). The post-treatment lingering effect was assessed at day 10 (3 days after treatment) and at day 14 (7 days after treatment). The corneofungimetry bioassay was performed on these CSSS to assess the antifungal profile of R126638. Cells of different fungal species (Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, Candida albicans and Malassezia globosa) were deposited and cultured for 10 days on CSSS in a sterile and controlled environment. The extent of fungal growth on the stratum corneum was determined using computerized image analysis. RESULTS: R126638 clearly reduced the growth of all tested fungal species. The onset of effects of R126638 was evidenced at day 4 when it reached statistical significance for 3 of 5 species. At day 7, significance was reached for 4 of 5 species. During the posttreatment period, R126638 remained effective for 4 of 5 species at day 10, and this activity persisted until day 14 for 2 of 5 species. CONCLUSION: A broad spectrum antifungal activity was rapidly expressed in the stratum corneum after oral intake of R126638. The drug likely reached the upper layers of the stratum corneum by diffusion and persisted in this location for at least 7 days after treatment.

Corneofungimetry bioassay on Malassezia spp. under ketoconazole and desonide influences.

BACKGROUND: Glucocorticoids can boost some Malassezia-driven dermatoses. However, both antifungals and topical corticosteroids improve lesions of seborrheic dermatitis. OBJECTIVE: To revisit the topical activity of the antifungal ketoconazole and the corticosteroid desonide on Malassezia growth on human stratum corneum. MATERIAL AND METHODS: The computer-assisted corneofungimetry bioassay was used to compare the growth of M. furfur, M. globosa and M. restricta on human stratum corneum coated with olive oil. Four blinded gel formulations were tested. They contained either 2% ketoconazole, 0.05% desonide or a combination of 2% ketoconazole and 0.05% desonide; one gel was unmedicated. Untreated stratum corneum and specimens coated with a 2% ketoconazole cream were used as negative and positive comparators, respectively. A total of 45 samples (15 M. furfur, 15 M. globosa, and 15 M. restricta) were used for each test formulation in this randomized, double-blind study. RESULTS: The 2% ketoconazole gel and cream and the combination of 2% ketoconazole and 0.05% desonide formulation abated similarly and significantly the M. furfur, M. globosa and M. restricta growth. The 3 species were similarly sensitive to these formulations. By contrast, no significant inhibitory effect was yielded by the 0.05% desonide gel and the vehicle. CONCLUSION: The presence of 0.05% desonide does not impair or improve the Malassezia susceptibility to 2% ketoconazole when growing on lipid-enriched human stratum corneum.

Comparative anti-dandruff efficacy between a tar and a non-tar shampoo.

A randomized double-blind clinical study was conducted on two groups of 30 volunteers using either a non-tar shampoo (2% salicylic acid, 0.75% piroctone olamine and 0.5% elubiol) or a 0.5% coal tar shampoo. Subjects were diagnosed as having moderate to marked dandruff. The study consisted of a 3-week washout, followed by a 4-week treatment and a 4-week posttreatment regression phase. The clinical evaluations and subject self-assessments showed that the non-tar shampoo was as effective as the tar shampoo. Both received high approval ratings (> or =70%). Biometrological methods proved to be more sensitive than clinical evaluations to assess the efficacy of the shampoos. The non-tar shampoo yielded a significantly better reduction of Malassezia spp. counts (p<0.02) during the treatment phase and reduced the spontaneous increase in squamometry values (p< 0.01) during the posttreatment phase. It is concluded that a formulation associating salicylic acid, piroctone olamine and elubiol exhibited increased beneficial effects compared to the coal tar shampoo.

A randomized, placebo-controlled trial of topical retinol in the treatment of cellulite.

BACKGROUND: Cellulite occurs to varying degrees on the thighs and buttocks of many otherwise healthy women. Among the many purported treatments for cellulite, only a handful have been tested in clinical trials. OBJECTIVE: The aim of this study was to critically explore the reputed effect of topical retinol in the treatment of cellulite. MATERIALS AND METHODS: The study compared the effect of topical retinol to a placebo formulation in a left-right randomized trial in order to eliminate the massage-effect. The study was conducted in 15 women aged from 26 to 44 years who had requested liposuction to improve mild to moderate cellulite. RESULTS: After 6-months of treatment, skin elasticity was increased by 10.7% while viscosity was decreased by 15.8% at the retinol-treated site. Such an effect on the tensile properties of skin was more prominent where the mattress phenomenon was the only evidence of cellulite. The lumpy-bumpy appearance of the skin showed either little response or was not responsive to the treatment. Although gross microanatomical differences were not disclosed between the comparative sites at completion of the study, evidence for a shift in the phenotype of connective tissue cells was obtained. The main retinol-related change consisted of a 2- to 5-fold increase in the number of factor XIIIa+ dendrocytes both in the dermis and fibrous strands of the hypodermis. CONCLUSIONS: We hypothesize that the functional and phenotypic changes seen in this study were linked and represent the result of a direct or indirect modulating effect of retinol on cellulite. Such features ultimately improve the resting tensions inside the skin which should in turn smooth the skin surface.