[Assessment of the photosensitization potential of zinc gluconate]. / Evaluation du potentiel photosensibilisant du gluconate de zinc.

INTRODUCTION: Tolerance and clinical efficacy of zinc gluconate are well documented, however, no study have evaluated its photosensitizing potential. It is well known that many treatments of acne are photosensitizing. Evaluation of the photosensitizing potential of zinc gluconate was the aim of this study. PATIENTS AND METHOD: Two open, monocentric studies were carried out with acneic volunteers. The methodology used in this study was an adaptation from that existing for the evaluation of the photosensitizing potential of topical products. In the study of phototoxic potential, volunteers were exposed to 20 J/cm2 UVA and to 0.75 times MED, before and after administration of zinc gluconate. Clinical and colorimetric evaluations of reactions were then carried out 1, 24, 48 and 72 hrs after exposure. In the photoallergic potential study, during the first week of the induction phase, the volunteers were exposed to 2 times MED, and to 3 times the MED during the second and third week. Then during the challenge phase, they were exposed t o4 J/cm2 UVA and to 0.75 times MED. Zinc gluconate was administered throughout the study. Clinical and colorimetric evaluations of reactions were carried out 24, 48 and 72 hrs after exposure, only during the challenge phase. RESULTS: The majority of clinical scores measured on scales at 6 and 5 levels were equal to 0 and 0.5 (evaluation of the phototoxic potential) or all equal to 0 (evaluation of the photoallergic potential). Thus zinc gluconate did not induce phototoxic or photosensitive reactions, whatever the ultraviolet type used. DISCUSSION: Since zinc gluconate does not induce any photosensitive reaction, it could be prescribed during periods of exposure to sun.

Echographic assessment of corticosteroid-induced skin-thinning, including echogenicity measurement.

BACKGROUND/AIMS: Skin atrophy is one of the main side effects of long-term topical corticosteroid therapy. It has already been studied through ultrasound skin-thickness measurement. In this study, the quantification of dermal echogenicity was introduced to provide new information on this phenomenon. METHODS: Skin thinning induced by topical application (without occlusion) of the superpotent corticosteroid clobetasol propionate (0.05% lotion), was assessed by means of ultrasonography in terms of thickness and echogenicity. 15 healthy volunteers were treated for 6 weeks, 1 daily, 5 days a week on the forearms. RESULTS: The thinning showed a biphasic pattern, with a 1st period of rapid change (about 15% of thinning in a week) followed by a period of slower but significant change. Skin thickness returned to baseline values 3 weeks after the end of treatment. Dermal echogenicity, which represents the mean intensity of the ultrasound signals reflected by the dermis, was found to follow the same variations, increasing strongly during the 1st week, then more slowly. The 2 parameters are correlated and probably reflect the same physiological modifications responsible for skin thinning, i.e., a reduction in glycosaminoglycan synthesis (leading to a drastic fall in dermal water content) and vasoconstriction. CONCLUSION: This sensitive and non invasive method enables us to identify the effects of clobetasol propionate on the healthy dermis in the absence of any clinical signs of thinning.

Colorimetric assessment of the effects of azelaic acid on light-induced skin pigmentation.

A 20% azelaic acid (AZA) cream is currently used as a therapeutic agent in the treatment of acne vulgaris. Therefore, this product is intended to be applied on frequently or continuously sun-exposed skin. In certain disorders of hyperpigmentation, AZA has been reported to have a depigmenting effect as well, while showing no significant activity on normal skin. It has been suggested that AZA selectively inhibits hyperactive or malignant melanocytes. Knowing that light-stimulated melanocytes are in a state of hyperactivity, it seemed worthwhile to investigate AZA activity on light-induced skin pigmentation. This study aimed to assess the activity of 20% AZA cream on light-induced skin pigmentation in 10 subjects. There were 5 test zones, all located on the middle of the back: 2 were treated with AZA cream, 2 others with the vehicle and 1 was left untreated. Each product was applied twice daily, 5 days a week, for 4 weeks on one zone, and for 5 weeks on the other. In the middle of the fourth week, the tested zones were exposed to ultraviolet B (UVB) + UVA + visible light, with a total of 3 times the minimal erythema dose distributed progressively over 3 consecutive days. Seven and 10 days after the last irradiation, the induced photopigmentation was assessed by colorimetric and visual means. Compared with its vehicle, the AZA cream had neither a depigmenting effect nor a preventive effect on the light-acquired skin pigmentation. Moreover, interrupting or continuing the AZA treatment after skin irradiation had no influence on the resulting pigmentation.

Processing and statistical analysis of laser Doppler data applied to the assessment of systemic anti-inflammatory drugs.

Continuous laser Doppler measurements of methyl nicotinate-induced skin inflammation have been used to evaluate the activities of three oral non-steroidal anti-inflammatory drugs, indomethacin 50 mg (Indocid), tiaprofenic acid 100 mg (Surgam) and sodium acetylsalicylate 1 g (Catalgine). They were compared in a single-blind, randomized, intra-individual comparison (N = 16) versus placebo (lactose). One hour after each drug was ingested, four concentrations of methyl nicotinate were applied to the subject's forearms. Simultaneous skin blood flow (SBF) measurements were then carried out on the four tested zones, by use of four calibrated laser Doppler flowmeters. Computerized processing of recorded SBF levels provided data related to flow amplitude, kinetics and magnitude (area under the curve) of the reactions. A detailed statistical analysis was performed to establish the selectivity of this type of test and the following points were demonstrated: adjustment of SBF data to baseline did not improve precision, data had to be log-transformed before analysis, and magnitude data gave the best product discrimination. Under the conditions of this study, i.e. one hour after oral administration and for the indicated doses, the tested products could be classified, in terms of anti-inflammatory activity, as follows: Lactose less than Indomethacin 50 mg = Tiaprofenic acid 100 mg less than Sodium acetylsalicylate 1 g.

Objective assessment of topical corticosteroids and non-steroidal anti-inflammatory drugs in methyl-nicotinate-induced skin inflammation.

The aim of this study was to compare the activities of the two main classes of topical anti-inflammatory drugs in methyl-nicotinate-induced skin inflammation, using a new methodology based on laser-Doppler velocimetry. Six topical non-steroidal anti-inflammatory drugs (NSAIDs) (bufexamac, diclofenac, ibuprofen, indomethacin, phenylbutazone and niflumic acid) and three topical corticosteroids (clobetasol propionate, hydrocortisone and hydrocortisone butyrate) were tested. Drugs were commercially available (except indomethacin) and were applied under occlusion for 4 h to the forearms of 16 healthy male volunteers. Thirty minutes after excess drug removal, skin inflammation was induced by a 1-min application of methyl nicotinate (3 mM). This was repeated 44 h later. Each methyl-nicotinate application was followed by continuous skin blood flow recordings over 1 h. Overall, NSAIDs proved more effective than corticosteroids in inhibiting methyl-nicotinate-induced increases in skin blood flow. Diclofenac and indomethacin showed a potent prolonged inhibitory effect. Different types of activity were observed in the corticosteroid group: (a) At 30 min, hydrocortisone and hydrocortisone butyrate moderately inhibited methyl-nicotinate reactions whereas clobetasol propionate produced no detectable effects; (b) at 44 h, clobetasol propionate produced a significant inhibition whereas hydrocortisone butyrate and hydrocortisone exhibited either weak or no inhibitory action at all. These pharmacodynamic discrepancies between the corticosteroids tested could be related to differences in drug affinity to cutaneous receptors and in vasoconstrictive potency.

Objective assessment of topical anti-inflammatory drug activity on experimentally induced nickel contact dermatitis: comparison between visual scoring, colorimetry, laser Doppler velocimetry and transepidermal water loss.

Four topical anti-inflammatory drugs were investigated for their effect on allergic contact dermatitis. Nickel dermatitis was chosen for its high incidence in European healthy volunteers. Experimental lesions were treated twice daily with two steroids, two non-steroidal anti-inflammatory drugs and a blank base for 4.5 days without occlusion. The influence of treatments was assessed by daily visual grading and one site was left untreated for comparison over the same period. To quantify drug activities objectively, skin colour (colorimetry), skin blood flow (laser Doppler velocimetry) and transepidermal water loss (evaporimetry) were measured before drugs were first applied, then 6 hr after the last application. As expected, only Dermoval cream significantly improved the spontaneous clinical evolution in comparison with the other creams (Hydrocortisone Aster à 1%. Parfenac, indomethacin 2.5% and Skinbase) and the untreated site. Colorimetric parameter a* (redness) and L* (luminance) showed more differences between treatments than the other criteria and a close relationship was obtained between these two parameters and skin blood flow, all three being highly correlated to visual grading. Transepidermal water loss appeared less related to clinical improvement but this parameter could prove helpful for detecting compounds which could be irritant to diseased skin.