Skin pharmacology : the official journal of the Skin Pharmacology Society最新文献

Tamol is widely used in the therapy of inflammatory dermatoses. It has pronounced astringent properties and is able to inactivate the neutrophil-derived elastase. Since plasminogen activation and release of mast cell chymase may occur in acute dermatitis, we investigated the inhibitory properties of tamol for these enzymes. Tamol proved to be a potent inhibitor of plasmin and mast cell chymase in concentrations relevant for use in dermatotherapy. The inhibition of mast cell chymase and plasmin by tamol was linear and non-competitive. The inactivation of proteolytic enzymes with the capacity to degrade extracellular-matrix proteins may be one of the major clinical effects of tamol in the treatment of acute inflammatory dermatoses.

We examined the influence of melatonin, serotonin and tryptophan on the basal and delta-aminolevulinic acid (ALA)-induced porphyrin content in HaCaT, SKMel-23 and HepG2 cells. ALA-preincubated and ALA-free cells were fed with medium containing 1 mM melatonin, serotonin or tryptophan. After 24 h the porphyrin content in the cells and in the culture medium was measured. In the three cell lines the inbucation with 1 mM ALA over 24 h increased the porphyrin concentration in all cell lines in different degrees: HepG2 > SKMel-23 > HaCaT cells. In HepG2 cells, neither melatonin, serotonin nor tryptophan influenced ALA-induced porphyrin concentrations significantly, but all three indoles depressed the porphyrin levels in SKMel-23 and HaCaT cells. The indoles may decrease the ALA uptake in HaCat or SKMel-23 cells. Another mechanism could be the inhibition of enzymes converting ALA into porphyrins.

The in vitro antifungal activity of the new hydroxypyridone antimycotic rilopirox has been evaluated against 29 separate clinical isolates of Malassezia (M.) furfur obtained from patients with pityriasis versicolor, seborrhoeic dermatitis or dandruff. Minimum inhibitory concentrations (MICs) of rilopirox were measured by the agar dilution technique and, in comparison, by a recently described microdilution method with colorimetric detection of the MIC end points. Rilopirox was found to be able to inhibit growth of all clinical yeast isolates. For the investigated M. furfur strains MIC values from 12.5 to 50 micrograms ml-1 with a median of 25 micrograms ml-1 were determined by the agar dilution method. Using the microdilution technique, MIC values between 16 and 128 micrograms ml-1 (median 32 micrograms ml-1) were found for the M furfur isolates. It has to be taken into account that with a 0.3% solution concentrations of 300,000 micrograms ml-1 are applied to the skin. Furthermore, due to its extreme low penetration rilopirox is long-term available in the skin in inhibiting concentrations. In comparison with rilopirox, the in vitro susceptibility of M. furfur against the systemically applicable triazole antimycotic itraconazole and clotrimazole, an established topical antifungal, was tested. As expected, low MIC values for these azoles were found by the agar dilution method. The median of the MIC of M. furfur was 0.1 microgram ml-1 for itraconazole, and 6.25 micrograms ml-1 for clotrimazole. The inhibitory effectivity of rilopirox against clinical isolates of M. furfur seems to justify its therapeutic evaluation in clinical trials. This new antifungal may be a useful alternative not only in pityriasis versicolor but also in seborrhoeic dermatitis due to the growth inhibition of M. furfur.

The effect of topical application of clobetasol propionate ointment (0.05% w/v) on the vascular changes induced by intradermal injections of histamine, calcitonin gene-related peptide, substance P, endothelin-1 and compound 48/80 was studied. Clobetasol propionate ointment was applied topically under occlusion to the forearm skin of healthy volunteers and vehicle base was applied to the contralateral forearm. The intradermal injections were made 4 h or, in a separate study, 72 h after topical steroid application. Responses were measured by planimetry and laser Doppler flowmetry. Four hours application of steroid did not significantly alter the responses to any of the vasoactive substances. After 72 hours application, clobetasol propionate significantly increased the size of the endothelin-1-induced area of vasoconstriction (p < 0.02) and significantly reduced the size of the flares induced by endothelin-1 (p < 0.02), substance P (p < 0.009) and compound 48/80 (p < 0.05). We conclude that the most likely explanation of our data is an inhibition by the steroid of cutaneous mast cell function.

A model has been developed to determine the effectiveness of topical antipruritics. It utilizes controlled, experimentally induced itch and has demonstrated the effectiveness of the direct action on cutaneous receptor sites of a topical anesthetic, benzocaine, in a topical antipruritic formulation, and has been used to differentiate between two effective topical antipruritics. Three studies are presented: The first study examined the reliability of the experimentally induced itch. Several indices of reliability were computed from the data of this first study. Cronbach's alpha was 0.92. Winer's theta also was 0.92. Simple test-retest reliability, computed at intervals of 29 min, 1 day, and 6-7 days, resulted in Pearson correlations of 0.84, 0.73, and 0.60, respectively. In the second study, the model differentiated statistically between the itch relief resulting from the topical application of a formulation with 6% benzocaine and the same formulation without benzocaine. The third study examined 2 known topical antipruritics: one containing 6% benzocaine and the other 1% hydrocortisone. Both topical antipruritics were found to relieve itch; however, the benzocaine antipruritic produced statistically significantly greater itch relief in more subjects than the hydrocortisone antipruritic at both 1 and 30 min after application. These results demonstrate that OTC antipruritics can be differentiated for effectiveness.

Erythromycin with or without additional zinc acetate is used topically in the treatment of acne vulgaris. A potential effect of zinc on the stratum corneum penetration of erythromycin was investigated in human volunteers. Skin surface washings and tape strippings from the skin of the back were collected after drug applications in 12 subjects for quantification of erythromycin levels. Zinc acetate increased the amount remaining on the back skin at 6 h after application from 40 +/- 19 to 56 +/- 15% of the dose and, vice versa, reduced the amount in stratum corneum strips from 22 +/- 7 to 18 +/- 7%, both with statistical significance. The effect varied with body region. Zinc acetate thus provided to prolong the residence time of erythromycin on the skin.

In the present study we have investigated the effects of diethylene glycol monoethyl ether (Transcutol) in combination with theophylline, caffeine and dyphylline and alone on 3T3 mouse fibroblast proliferation. These three xanthines (1-0.01 mM) inhibited fibroblast proliferation by themselves. Enhancement of the effect was detected by addition of 1 and 0.1 mM Transcutol. Transcutol alone also displayed a dose-dependent inhibition (2-0.01 mM) of both 3T3 and human normal and psoriatic fibroblasts, although normal human fibroblasts were the least sensitive to Transcutol antiproliferative activity. Transcutol was assessed for its antiproliferative effects on YAC lymphoma and P-815 mastocytoma human cell lines. Transcutol inhibited cell proliferation of both these cell lines, being more effective towards P-815 mastocytoma (at 2 mM it displayed 3.95-fold vs. 2.4-fold inhibition towards YAC lymphoma). In conclusion, we have shown that Transcutol has antiproliferative effects on 3T3 murine, human normal and psoriatic fibroblasts and tumour cell lines. In addition it enhances xanthine antiproliferative effects on 3T3 fibroblasts. Therefore it might be a useful topical drug alone or in combination with xanthines in the treatment of skin hyperproliferative disorders.

Previously, we described methods for measuring in vivo antimicrobial activity in which the resident bacterial flora of the forearm is expanded by occlusion with an impermeable plastic film, test agents are applied and quantitative cultures are obtained at varying time points. This methodology allows for an in vivo quantitative assessment of antimicrobial effects directed against a dense flora comprised primarily of staphylococci. This method may not be applicable to situations in which there is a high density of multiple species of bacteria. We describe herein new methods which permit in vivo determination of antimicrobial activity against a dense, mixed flora. Swabs moistened with a dilute nonionic detergent are used to remove bacteria from the subject's axilla or groin which are then translocated to the subject's forearm. Occlusion of the forearm with a large, sterile plastic chamber provides the necessary humid environment to yield a dense flora (10(5)-10(6) CFU) consisting of gram-positive cocci, gram-positive coryneforms and gram-negative rods. In this manner, multiple test sites are created on each forearm allowing for the simultaneous evaluation of multiple antimicrobial agents in a single subject. This method allows for the evaluation of the immediate, as well as sustained, in vivo bactericidal effect of an antimicrobial agent against a dense mixed flora with quantitative cultures obtained at varying time points after application of the test agent. Furthermore, ecological pressures which select for resistant organisms or allow for an overgrowth of nonsensitive bacteria can be evaluated by determining the composition of the flora after single or repeated applications of a test agent. The testing methodologies described herein can provide relevant information regarding the antimicrobial effectiveness of an agent in a variety of situations such as use against the axillary flora (including its utility as a deodorant), use as a perineal cleanser for critically ill, hospitalized patients and use in situations where a dense mixed flora exists, e.g. stasis ulcers and infected intertriginous dermatoses.