摘要:

In order to define the respective involvement of steroidogenesis enzymes subtypes in the control of hair follicle homeostasis, we evaluated, by semiquantitative RT/PCR, the expression levels of mRNAs coding for 17 β-hydroxysteroid dehydrogenase type 1 and type 2, 3β-hydroxysteroid dehydrogenase, Cyt.P450-aromatase, steroid 5α-reductase type 1 and type 2 and 11 β-hydroxysteroid dehydrogenase. These assays were performed for several components of the pilosebaceous unit (PSU); fresh plucked anagen hairs, sebaceous glands and primary culture of dermal papilla, as well as other tissues involved in an active steroid metabolism (human testis, liver, placenta, prostate, ovary, uterus and adrenals) as controls. We found that plucked hair (i.e. mainly keratinocytes from the inner and outer root sheaths) expressed: (1) very high levels of 17β-hydroxysteroid dehydrogenase type 2 corresponding to levels found in liver and placenta; (2) high levels of steroid 5-α-reductase type 1 corresponding to levels found in testis, liver and ovary, and moderate levels of 17 β-hydroxysteroid dehydrogenase type 1, which corresponded to the expression in testis, prostate and uterus. In contrast, Cyt.P450-aromatase, 3β-hydroxysteroid dehydrogenase and steroid 5α-reductase type 2 were poorly expressed in the pilosebaceous unit as compared with other tissues. Interestingly, expression patterns of these enzymes in primary cultures of dermal papilla were distinctive since 5α-reductase type 1 and 11 β-hydroxysteroid dehydrogenase were the only mRNA detected. Taken together, these results suggest that not only sebaceous gland but also outer root sheath keratinocytes may contribute, through the activity of the steroid 5α-reductase type 1, to the pathogenesis of androgen-depende

ISSN:1660-5527    

DOI:10.1159/000211412

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

It has been previously reported that minoxidil inhibits the activity of lysyl hydroxylase (LH), an enzyme which catalyzes the formation of hydroxylysine, which is necessary for proper maturation of collagen at the transcriptional and enzymatic levels. Using the reverse transcriptase-polymerase chain reaction, we confirmed that this inhibition occurred at least at the transcriptional level. Furthermore, we took advantage of this sensitive and rapid method to perform a quantitative structure activity relation study using several compounds structurally related to minoxidil. We found that when the C6 of the pyrimidinyl moiety was substituted, it had to be by a tertiary nitrogen, i.e. an N-piperidin ring for the inhibition of LH mRNA synthesis to be observed. Surprisingly, however, we found that 2,4-diamino-pyrimidin-3-oxide, a new compound lacking an organic moiety para to the nitroxide oxygen, also retained a high inhibitory effect on LH mRNA expression, comparable to that of minoxidil. We thus conclude that the presence of a substituent para to the nitroxide oxygen is dispensable for inhibition of LH mRNA to be observed in vitro. This brings new insights into the design of therapeutic agents useful in any condition where an overproduction of mature collagen is unwanted, i.e. accelerated wound healing, keloids and localized scleroderma.

ISSN:1660-5527    

DOI:10.1159/000211413

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

A new method for an objective assessment of the gloss of human skin is presented. The refiectometric measuring set-up complies with DIN 67530. The principle of this new method is based on a contactless determination of the skin’s reflection of light from a tungsten filament lamp, recorded at an angle of 60° by a silicon photocell. In a comparative study with 30 test persons it was discovered that the forehead, with 2.70 standardised reflectometer units (RU; SD ± 0.59 RU), displayed a significantly higher gloss than the lower arm (1.99 RU, SD 0.28 RU, p < 0.0001). In an investigation into the influence of four different cream bases on the skin gloss it could be determined that the value depends on the percentage of grease, the water concentration and the consistency of the respective base. The method presented permits a fast, contactless, randomly repeatable objective assessment of skin gloss. Since the acceptance of cosmetics and pharmaceutical products depends not least on their skin gloss effect, this method can provide valuable information when estimating the success of old and new produ

ISSN:1660-5527    

DOI:10.1159/000211414

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Effective methods of fungal treatment involve reduction in fungal infections and host inflammatory responses. Naftifine (NF), a topical antifungal agent, is highly active in vitro and in vivo against a wide range of pathogenic fungi. Additionally NF has been shown to inhibit polymorphonuclear leukocyte (PMN) chemotaxis and respiratory burst activity in an irreversible dose-dependent and time-dependent manner. Since leukocyte adherence to endothelia is believed to be one of the initial crucial events in the recruitment of circulating leukocytes to the site of inflammation, we have investigated the in vitro effect of NF on PMN adherence to nylon fiber, BSA-coated glass chamber or polystyrene, and endothelial mono-layers via three adherence assays. All three assays demonstrated a statistically significant reduction (p < 0.01-0.001) in PMN adherence to the respective media. In particular, NF (at 30-60 μg/ml) significantly inhibited PMN adherence to endothelial monolayers (p < 0.01) as measured spectrophotometrically by the uptake of rose bengal stain. Therefore, NF inhibits PMN adherence to endothelia in our in vitro model system. This inhibition may constitute part of the anti-inflammatory effect of NF

ISSN:1660-5527    

DOI:10.1159/000211415

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The accidental or therapeutic exposure of human skin to ionizing radiation is known to cause the radiation syndrome with its various manifestations. The aim of the study was to investigate the potential radioprotective effects of the protein-free hemodialysate Actovegin. After exposure to X-rays (single dose, 6 Gy), 70% of the cells died. In the presence of the hemodialysate, irradiation did not lead to cell death. Instead a slight increase in cell number was observed. A 5-fold increased cell number was found after 6 days when the cells were treated with the hemodialysate alone. To elucidate molecular mechanisms of the observed biological effects the correlation between the expression of the epidermal growth factor receptor (EGFR) and the demonstrated growth activation was investigated. Radiation alone resulted in a clear induction of EGFR, whereas the combination of irradiation and Actovegin treatment led to a strong downregulation after 2 days. Thus, the hemodialysate suppressed one of the radiation-induced effects. Further investigations have to elucidate the role of other proteins which are involved in the signal transduction cascade of tyrosine kinases (e.g. Ras, Raf, MAP kinases) leading to the transcription factor AP-1 in response to radiation under Actovegin treatment.

ISSN:1660-5527    

DOI:10.1159/000211416

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The effects of mild inflammation induced by topical chloroform treatment on plasma extravasation and mast cell response were studied in normal innervated and denervated rat skin. In the absence of inflammation, the reduction in plasma protein extravasation in response to noxious heat was 31.2% in denervated skin compared to the innervated skin. In the presence of inflammation, the reduction in this response was 52.5% in denervated skin compared to the innervated skin. During inflammation, mast cells became abundant, highly degranulated and migrated to the lower dermal tissue forming large aggregations. The ultrastructural observations showed a close anatomical relationship between mast cells and vesicle-containing nerve profiles. These results indicate that repeated topical chloroform treatment of the rat skin induces neurogenic vascular inflammation accompanied by an increase in mast cell response.

ISSN:1660-5527    

DOI:10.1159/000211417

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Skin mast cells and basophilic leukocytes are known as key elements of acute and subacute IgE-mediated immune responses of the skin. The present paper investigated pharmacological aspects of signal transduction pathways of both cell types using activators and inhibitors of protein kinase C (PKC). The nonselective inhibitor K252a suppressed FcεRI-mediated histamine release from basophils and skin mast cells dose-dependently with IC50 values of 0.01 and 0.28 μmol/l. However, preincubation of both cell populations with kinase inhibitors showing in vitro selectivity for PKC (Ro 31-7549, calphostin C, GF 109203X) revealed a distinct modulation of cell response: IgE-mediated mediator release was inhibited only in skin mast cells, whereas in experiments with basophils a concentration-dependent potentiation of exocytosis was observed. Further evidence for heterogenous biochemical signals following activation of both cell types derived from studies with the phorbol ester TPA. With respect to acute and late-phase IgE-mediated skin reactions, we suggest that distinct signal transduction mechanisms at the level of PKC (isozymes) in basophils and skin mast cells might reflect their functional heterogeneit

ISSN:1660-5527    

DOI:10.1159/000211418

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The effect of dose and enzymatic inhibition on the percutaneous absorption and metabolism of benzocaine was studied in vitro in the hairless guinea pig. At the dose level of 2 μg/cm2, benzocaine was rapidly absorbed and extensively metabolized (80%) by acetyltransferase. As the applied dose of benzocaine was increased to 40 and 200 μg/cm2, N-acetylation of benzocaine decreased to 44 and 34%, respectively, suggesting saturation of the acetyltransferase system. Total 14C absorption after benzocaine application was not significantly different between control and enzyme-inhibited skin and therefore does not appear to be affected by the extent of benzocaine metabolism during percutaneous penetration. Skin provides a significant first-pass metabolic effect for therapeutic doses of percutaneously absorbed benzocaine, and the primary metabolite formed, acetylbenzocaine, is biologically activ

ISSN:1660-5527    

DOI:10.1159/000211419

出版商:S. Karger AG    

年代:1996

数据来源: Karger