摘要:

There is much evidence to support the theory that keratino-cytes and dermal fibroblasts actively participate in inflammatory reactions by the production of proinflamrnatory mediators or cytokines. We investigated the neutrophil chemotactic activity in conditioned media of cultured epidermal cells and dermal fibroblasts, and found that an epidermal cell-derived factor induced fibroblasts to produce a neutrophil chemotactic factor. This neutrophil chemotactic factor was identified as interleukin-8 (IL-8) by the elution position on HPLC and by a neutralization test that uses monoclonal anti-IL-8 antibody (14E4). The epidermal cell-derived factor was fractionated together with thymocyte-proliferating activity on Sephadex G-75 gel chromatography followed by HPLC. It was blocked specifically by anti-interleukin-1 (IL-1) α antibody, which indicates that this factor was IL-1α. Since a variety of inflammatory dermatoses is characterized by the infiltration of neutro-phils into the skin, induction of IL-8 production in fibroblasts by epidermal cells may play an important role in inflammatory skin diseases.

ISSN:0302-3427    

DOI:10.1159/000211129

出版商:S. Karger AG    

年代:1993

数据来源: Karger

ISSN:0302-3427    

DOI:10.1159/000211130

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

We have conducted studies using primary mouse epidermal keratinocyte and whole hair follicle cultures to investigate the mechanism of the hypertrichotic activity of potassium channel openers. In a time course study, the extent of stimulation of epidermal keratinocyte DNA synthesis by minoxidil increased as the rate of DNA synthesis in control cultures declined. Minoxidil stimulation of DNA synthesis in 7-day cultures required prolonged (> 1 day) exposure to the agent. Pinacidil and diazoxide also stimulated DNA synthesis in mouse epidermal keratinocyte cultures. In addition, minoxidil, pinacidil, diazoxide, and cromakalim stimulated DNA synthesis in whole-organ cultures of mouse hair follicles. These results suggest that potassium channel openers retard the loss of proliferative activity of differentiating keratinocytes and support the hypothesis that these agents stimulate hair growth through a direct effect on hair follicles.

ISSN:0302-3427    

DOI:10.1159/000211131

出版商:S. Karger AG    

年代:1993

数据来源: Karger

ISSN:0302-3427    

DOI:10.1159/000211132

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Prednicarbate (PC) is a nonhalogenated derivative of prednisolone which is used for the local treatment of corticoid-sensitive skin diseases. In this study, the pharmacokinetics and the metabolism of PC in humans are investigated after cutaneous ointment application (75 mg PC) and after systemic oral administration (40 mg PC) in 8 healthy volunteers. In addition, the possible suppression of endogenous cortisol secretion by both application forms was monitored. After oral administration no intact PC, but significant levels of the first metabolite prednisolone-17-ethylcarbon-ate (PRED-17-EC) were determined. PRED-17-EC was further metabolized with a half life of 1.6 h to prednisolone. After percutaneous administration neither PC nor other known metabolites could be detected system-ically. The low systemic bioavailability after dermal application was also reflected in an unchanged cortisol secretion pattern. According to animal studies our metabolic studies in humans suggest that the prednisolone-17-ester PRED-17-EC, which has a receptor binding affinity comparable to that of dexamethasone is the pharmacologically active compound. As PRED-17-EC subsequently undergoes an inactivation step to the low active prednisolone this may be the reason for the dissociation of good local efficacy and low systemic side effects.

ISSN:0302-3427    

DOI:10.1159/000211133

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The bioactivity of a novel topical glucocorticosteroid, mometasone furoate 0.1 % fatty cream was compared with betamethasone dipropionate 0.05% cream and betametasone valerate 0.1% cream. An ultraviolet light (UV-B)-induced inflammation assay in humans was used, and the combined effect of a single, open application of the corticosteroids was evaluated. Reduction of UV-B induced inflammation was monitored by laser Doppler blood flowmetry, clinical skin scoring and skin reflectance spectrophotometry. Skin scoring and reflectance spectrophotometry were found unsuitable because one of the cream vehicles contained titanium dioxide which shielded skin erythema. Laser Doppler blood flowmetry showed that mometasone furoate 0.1 % fatty cream was more than twofold better in reducing UV-B-induced inflammation than betamethasone dipropionate 0.05% cream and betametasone valerate 0.1 % cream, and that the effect was sustained for at least 24 h after a single application.

ISSN:0302-3427    

DOI:10.1159/000211134

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Published data (mainly from rodent skin) suggest a correlation between compounds which inhibit protein kinase C (PKC), have anti-inflammatory or antitumor characteristics and possess antipsoriatic potential. We have investigated the effects of topical application of sphingosine (a naturally occurring PKC inhibitor), isoquinoline (a component of coal tar which showed antipsoriatic capacities in the mouse tail model) and tannic acid (a plant phenol with antitumor activity) on human skin. In each case we have assessed (a) the level of induction of ornithine decarboxylase (ODC) following Sellotape® stripping as an indicator for potential PKC inhibition in vivo, and (b) its effects on the lesions of chronic plaque psoriasis. The control group consisted of 18 healthy volunteers, used for the ODC induction experiments (0.0/0.1/0.2 M sphingosine in ethanol, 100% coal tar and 0/50 mM tannic acid in acetone) and 17 psoriatic patients used for double-blind scoring of two randomly selected lesions (0.0/0.1 M sphingosine in ethanol, 0.0/0.2% isoquinoline in white vaseline/lanette wax cream 50%/50% and 0/10% tannic acid in lanette wax cream) and also for some of the ODC induction experiments (0.0/0.2% isoquinoline and 0/10% tannic acid). Biopsies were taken 8 h after stripping and ODC activity was assessed by measurement of 14CO2 release. Lesions were scored with a modified psoriasis area and severity index on days 0,7 (isoquinoline and tannic acid), 13 (sphingosine) and 21 (isoquinoline and tannic acid). Application of 0.1 or 0.2 M sphingosine resulted in a decrease of ODC activity of 52% and 66%, respectively (p 0.05). All compounds failed to show significant improvement of the psoriatic lesions. Therefore we may conclude that ‘theoretical’ antipsoriatic agents may be limited in practice by cytotoxicity and hence a narrow therapeutic index, poor penetration and lack of specificity. Further, a marked difference between the effects of these compounds on the skin of different species increases the difficulty of predicting antipsoriatic acti

ISSN:0302-3427    

DOI:10.1159/000211135

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

This study compared in man the in vivo barrier function of stratum corneum in three racial groups: black, Caucasian and Asian, by two noninvasive technics. They were transepidermal water loss (TEWL) determination measured with an evaporimeter and laser Doppler velocimetry (LDV) to measure the lag time before the vasodilatation induced by application of methyl nicotinate (10 μl of 0.5% solution in ethanol/propylene glycol 95/5 v/v). Both methods were performed simultaneously on each forearm of 7 black, 8 Caucasian and 6 Asian subjects before and after removal of the stratum corneum by stripping. TEWL measurements were higher (p < 0.01) in Asians and Blacks compared to Caucasians. Stripping (8 or 12 strips) increased TEWL in all groups; TEWL increase percentage was higher (p < 0.05) in Asians compared to Caucasians. Vasodilatation lag times assessed by LDV showed that skin permeability was more important in Asians (p < 0.01) and in Caucasians (p black. Our study showed that, with both noninvasive methods, removal of the stratum corneum increased permeability, with racial differences

ISSN:0302-3427    

DOI:10.1159/000211136

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

We present a combined method of culturing pathogenic der-matophytes and yeasts on human stratum corneum. Topical marketed antifungals are applied in vivo, and the stratum corneum is removed by cyanoacrylate skin surface strippings. After inoculation of the test organism, the extent of fungal growth is measured, indicating by comparison with controls the level of inhibitory effect of the antifungal. Other samples of stratum corneum collected at different time intervals after the arrest of antimicrobial treatment are used to evaluate the lingering effect of the drug. The combination of the data gained by these approaches close to the in vivo situation is used to introduce a classification of antifungals.

ISSN:0302-3427    

DOI:10.1159/000211137

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Recent data have shown both synergistic and inhibitory effects between calcitonin gene-related peptide (CGRP) and substance P (SP) on inflammation and flare responses. The modulatory effects of CGRP on the itch, flare and weal responses following intracutaneous injections of SP and histamine were studied in 10 healthy volunteers. The only change in itch responsiveness observed was a significant prolongation of itch latency following SP when preceded 10 min earlier by a CGRP injection. No influence on flare and weal was observed.

ISSN:0302-3427    

DOI:10.1159/000211138

出版商:S. Karger AG    

年代:1993

数据来源: Karger