摘要:

Dithranol is highly effective in the treatment of psoriasis. The drug inhibits keratinocyte hyperproliferation, granulocyte function and, in addition, may exert an immunosuppressive effect. Free radicals, histamine, eicosanoids and platelet-activating factor have been shown to be involved in dithranol-induced dermatitis, and the oxidation products of the drug are responsible for the staining. Our experimental data suggest that extracellularly generated oxygen free radicals are responsible for both the antipsoriatic and irritative effect of the drug. Furthermore, we could recently provide evidence that extracellularly generated superoxide anion radical also induces an active adaptation mechanism resulting in increased tolerance to dithranol upon repeated application. This adaptive process may explain the requirement for increasing dithranol concentrations to maintain the antipsoriatic efficacy, and also the beneficial effect of other antipsoriatic modalities such as UV-B on dithranol-induced dermatitis. The recognition of this adaptive mechanism may open future prospects to overcome some limitations concerning the practical use of dithranol.

ISSN:1660-5527    

DOI:10.1159/000210836

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The kinetics and extent of uptake of ciclosporin in various strata of hairless mouse skin upon topical application of several ciclosporin formulations were determined by in vitro diffusion cell experiments. The ciclosporin formulations tested included a hydroalcoholic solution, an oil-in-water emulsion and two liposomal systems. The accumulation of drug in stratum corneum is in the order: ‘skin lipid’ liposomes > ‘phospholipid’ liposomes > emulsion > hydroalcoholic solution. The total combined amount of drug in the deeper skin strata and the receiver compartment followed the order: hydroalcoholic solution > > ‘phospholipid’ liposomes > ‘skin lipid’ liposomes > emulsion. The results suggest that topically applied liposomes, particularly those prepared from lipid mixutres having compositions similar to the stratum corneum, may provide sustained, enhanced levels of ciclosporin in the stratum corneum (the reservoir) while minimizing high levels in strata associated with blood and

ISSN:1660-5527    

DOI:10.1159/000210837

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The possible utility of DuP 654, a potent 5-lipoxygenase inhibitor, for treating human inflammatory skin disease was investigated in murine skin treated with 1.0 mg arachidonic acid (AA). When DuP 654 was applied to murine skin treated with AA, it inhibited the resulting inflammation and influx of cells. High performance liquid chromatography and radioimmunoassay analysis of lipid extracts from AA-treated ears indicated that the influx of polymorphonuclear leukocytes (PMN) was temporally preceded by an appearance of significant amounts of 5-HETE (6.7 ± 1.4 ng/ear) and Leukotriene B4 LTB4 0.92 ± 0.2 ng/ear) when compared with extracts of untreated ears (5-HETE, 02 ± 0.3 ng/ear; LTB4, < 0.1 ng/ear). The levels of the 5-lipoxygenase products were reduced by treatment with 10 µg/ear DuP 654. Lipid extracts from AA-treated ears contain chemotactic activity for human PMN and this chemotactic activity in the AA-treated ears could be reduced but not eliminated by immunosorption with anti-LTB4 antibodies coupled to protein A-agarose. The appearance of the chemotactic activity was inhibited by DuP 654. Taken together, these data suggest that DuP 654 may have utility in human inflammatory skin dise

ISSN:1660-5527    

DOI:10.1159/000210838

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The possible utility of DuP 654, a potent 5-lipoxygenase inhibitor, for treating human inflammatory skin disease was investigated in murine skin treated with 1.0 mg arachidonic acid (AA). When DuP 654 was applied to murine skin treated with AA, it inhibited the resulting inflammation and influx of cells. High performance liquid chromatography and radioimmunoassay analysis of lipid extracts from AA-treated ears indicated that the influx of polymorphonuclear leukocytes (PMN) was temporally preceded by an appearance of significant amounts of 5-HETE (6.7 ± 1.4 ng/ear) and Leukotriene B4 LTB4 0.92 ± 0.2 ng/ear) when compared with extracts of untreated ears (5-HETE, 02 ± 0.3 ng/ear; LTB4, < 0.1 ng/ear). The levels of the 5-lipoxygenase products were reduced by treatment with 10 µg/ear DuP 654. Lipid extracts from AA-treated ears contain chemotactic activity for human PMN and this chemotactic activity in the AA-treated ears could be reduced but not eliminated by immunosorption with anti-LTB4 antibodies coupled to protein A-agarose. The appearance of the chemotactic activity was inhibited by DuP 654. Taken together, these data suggest that DuP 654 may have utility in human inflammatory skin dise

ISSN:1660-5527    

DOI:10.1159/000316427

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Amide hydrolysis of indomethacin was investigated in rabbit skin using the isolated perfused rabbit ear model. Indomethacin was applied topically on the surface area of 4 rabbit ears using a 1 % alcoholic solution (Elmetacin®). Indomethacin and its hydrolytic product N-deschloro-benzoyl-indomethacin (DBI) were determined in the venous efflux. The concentrations of indomethacin and DBI increased during the first 160 min and remained constant thereafter, the concentrations amounting from 0.041 ± 0.001 to 0.497 ± 0.018 nmol/min/cm2 (indomethacin) and from 0.84 ± 0.03 to 3.24 ± 0.31 pmol/min/cm2 (DBI). Thus steady state was reached with both substances, indicating a formation of DBI in the range of 0.65–2.01 %. Considering the low hydrolytic turnover rate, the limited efficacy of topically applied indomethacin in the treatment of skin diseases does not seem to be due to extensive metabolic inactivation via amide hydrolysis in this target

ISSN:1660-5527    

DOI:10.1159/000210839

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000210840

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000210841

出版商:S. Karger AG    

年代:1990

数据来源: Karger