摘要:

In vivo histamine release in cutaneous allergic reactions was chronologically examined using the skin microdialysis technique. Antigen challenge was made in ovalbumin-sensitized guinea pigs 1 h after the implantation of the microdialysis probe. A marked histamine release after intradermal injection of ovalbumin solution was observed in the early phase (up to 40 min). No isolated delayed histamine release was observed thereafter over 8 h. Also, in an atopic volunteer, a marked release of histamine after intradermal injection of mite extract was observed only in the early phase, although erythema and induration at the site of injection were continuously observed in the late phase (up to 4 h). These findings suggest that the skin microdialysis technique is a useful, simple technique for chronological determination of chemical mediators released in the allergic skin in vivo.

ISSN:1660-5527    

DOI:10.1159/000211334

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

In this article, a new in vitro model system is presented with a multilayer membrane system serving as acceptor. Matrix-stabilized membranes are applied with dodecanol as lipid and collodion as matrix. Using the drug dithranol it was shown that the acceptor system can be varied over a wide range by changing the dodecanol content of the membranes and by addition of the hydrophilic substance propylene glycol to the membranes. It was demonstrated that the variability of the acceptor system can be used to adapt the penetration profiles of dithranol in a six-layer membrane system to those in excised human skin. It is shown that it is possible to study the penetration of dithranol from different semisolid formulations using the ‘adapted’ model system.

ISSN:1660-5527    

DOI:10.1159/000211335

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Benzoyl peroxide (BzPO) has been the most widely used topical agent for acne since the 1960s. This is true despite numerous reports that BzPO can enhance the development of carcinomas from murine epidermal papillo-mas. Because activation of protein kinase C (PKC) is considered to mediate cellular responses to other epidermal tumor promotors, we wished to investigate the relationship between BzPO and PKC in cultured human epidermal keratinocytes (NHEK). We assayed (a) direct effects of BzPO on PKC activity in a cell-free system using semipurified human keratinocyte PKC, (b) BzPO effects on the subcellular distribution of PKC, and (c) BzPO modulation of NHEK proliferation and phorbol ester-induced differentiation. NHEK maintained in serum-free media (0.15 mMCa2+) were treated with concentrations of BzPO in acetone from 100 nM to 500 μM, with concentrations of acetone not exceeding 0.1%. No short-term translocation of PKC from cytosol to membrane was observed at any BzPO concentration. BzPO did not downregulate subcellular levels of PKC activity after 24 h of exposure. BzPO did not significantly antagonize phorbol ester-induced inhibition of proliferation or differentiation but did weakly antagonize Ca2+-induced differentiation. Consistent with a PKC-mediated mechanism for Ca2+-induced differentiation, BzPO inhibited both human and murine PKC in a cell-free system. These results suggest that BzPO does not promote malignant conversion through a PKC-dependent mechanism, and in fact, inhibits PKC activity in vitro.

ISSN:1660-5527    

DOI:10.1159/000211336

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The effect of selenium on the lethal action of ultraviolet radiations and on the lipid peroxidation induced by exposures to ultraviolet A (320-400 nm; 360kJ·m-2) and ultraviolet B (290-320 nm; 2 kJ·m-2) have been measured in cultured human skin fibroblasts. The experiments have been performed with either pure selenium or a spring water containing selenium and other trace elements (zinc and strontium). For cells cultured in a standard medium containing 10% fetal calf serum, no effect of selenium or spring water addition to the culture medium was observed on the lethality or on the peroxi-dative process induced by ultraviolet A and B radiations. Concurrently, there was no detectable increase of the seleno-dependent glutathione peroxidase activity. For cells previously depleted in selenium by a culture in a medium containing only 2% serum, a protective effect of selenium can be detected. Depending on the fibroblast donor, we observed (1) a protective effect on lethality of dividing fibroblasts induced by ultraviolet A radiations, (2) a protective effect on lipid peroxidation induced by ultraviolet A radiations on dividing or quiescent fibroblasts and (3) an increase in glutathione peroxidase activity in fibroblasts.

ISSN:1660-5527    

DOI:10.1159/000211337

出版商:S. Karger AG    

年代:1995

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000211338

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Cyclosporine A (CsA) has been shown to be an effective therapeutic agent for a wide variety of cutaneous diseases yet its exact mechanism of action is still unclear, although one well-defined effect of CsA is the inhibition of T-cell-derived cytokine expression. We recently demonstrated in vitro that CsA inhibits cell proliferation and suppresses cytokine gene expression in keratinocytes. In this study, we report the in vivo effects of CsA on skin cytokine gene expression as determined by reverse-transcriptase polymerase chain reaction. C57BL6 mice (female, 8-10 weeks old) were subcutaneously injected with CsA in olive oil (0, 5 and 10 mg/kg) every other day for 3 weeks. Treatment with 5 mg/kg CsA inhibited both interleu-kin (IL)-1α and tumor necrosis factor α gene expression by about 70 and 90%, respectively, relative to vehicle control levels. However, IL-6 gene expression did not significantly change. Injection of 10 mg/kg CsA inhibited expression of all three genes by 80-90% relative to control levels. These data show that CsA can inhibit constitutive cytokine gene expression in mouse skin.

ISSN:1660-5527    

DOI:10.1159/000211339

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Porphyria cutanea tarda (PCX) is characterized by cutaneous symptoms in association with hepatic accumulation and urinary excretion of mainly uro- and heptacarboxyporphyrins. 24 PCX patients excreting urinary porphyrins between 1.9 and 5.8 μmol/24 h (normal < 0.2) were treated with chloroquine at a dose of 125 mg twice a week. During the first phase of therapy urinary porphyrin excretion transiently increased 1.1- to 2.9-fold indicating a phase of mobilization. A slight initial elevation was also found regarding the activities of serum amino-transferases reflecting the hepatotoxic effect of chloroquine. Xhe clinical symptoms disappeared after a period ranging from 2 to 6 months, and after an average of 12 months the porphyrin excretion in all patients had returned to nearly normal values.

ISSN:1660-5527    

DOI:10.1159/000211340

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Adult female Wistar rats divided into two groups (6 animals each) were subcutaneously treated with 105 units/day recombinant human interferon-α2b (hrIFN-α2b) and corresponding quantities of the vehicle, respectively, over a period of 7 days. Microsomal protein, P450 content, and the activities of ami-nopyrine-N-demethylase (ADM), 7-ethoxyresorufm-O-de-ethylase (7-ERO-D) and of erythromycin-N-demethylase (EMDM) were determined in the liver microsomes. Moreover, 7-ERO-D and EMDM activities were determined in the skin microsomes of the treated animals. In the liver microsomes hrIFN-α2b caused a statistically significant increase in ADM activity and a statistically significant decrease in 7-ERO-D and EMDM activities, as compared to the controls. However, in the pooled skin microsomes 7-ERO-D activity showed a trend to increase under the administration of hrIFN-α2b, whereas EMDM activity could not be detected in the treated or the control animals. The results of the present study indicate that hrIFN-α2b is capable of affecting the activities of P450-dependent isozymes in the rat liver and skin in a different manner. Our findings support the hypothesis that clinically relevant interactions may occur during the concomitant administration of hrIFN-α2b and other compounds that are metabolized by hepatic and cutaneous P450 monooxyge

ISSN:1660-5527    

DOI:10.1159/000211341

出版商:S. Karger AG    

年代:1995

数据来源: Karger