Case reports: tinea corporis in a 13-year-old German girl due to Trichophyton schoenleinii.

We report the first case of a tinea corporis with partly profound lesions in a 13-year-old girl on her arms, legs and trunk due to Trichophyton schoenleinii but without any lesion on scalp and hair. Moreover, this is the first case of an infection with Trichophyton schoenleinii in Germany since more than 40 years. The diagnosis was confirmed by microscopy of mycological specimens. Other causes of the skin symptoms could be excluded (atopic dermatitis, bacterial or other fungal infection). Clinical and epidemiological aspects of this anthropophile dermatophyte are briefly reviewed.

An improved and rapid method to construct skin equivalents from human hair follicles and fibroblasts.

To produce sufficient amounts of high quality skin equivalents (SE), either allogenic for dermatopharmacological and dermatotoxicological studies or autologous for transplantation purposes, we established a rapid, easy and cost effective three-dimensional SE model on the basis of human dermal fibroblasts, collagen and freshly plucked hair follicles. Acidic liquid collagen was polymerized with sodium hydroxide in the presence of fibroblasts to form a dermal equivalent (DE) resembling normal human dermis. At 24 h later, freshly plucked hair follicles were implanted into the surface of these DEs after cutting their bulbs off. Another 48 h later, the surface of the SEs was lifted to the air-liquid interface. Fourteen days after implantation, outgrowing keratinocytes from the outer root sheath of the hair follicles completely covered the surface of the SE and built a fully developed, multi-layered and cornified epidermis. Histology and immunofluorescence studies with specific antibodies directed against components of keratinocytes, fibroblasts, cell-adhesion molecules, different extracellular matrix and basement membrane proteins revealed the similarity of our three-dimensional SEs to the in vivo situation in normal human skin. Using autologous cell sources and cell culture media enriched with serum from the respective cell donor, it will be possible to use these SEs for autologous transplantation, thereby reducing the risk of transplant rejection.

Pharmacotherapy of ectoparasitic infections.

Epizoonoses such as scabies, lice and cimicosis are common, vexing disorders that occur worldwide. Historically, many treatment modalities have been employed in the management of these disorders, and most of the drugs described in this review are of historical interest and no longer recommended or in widespread use because of their wide spectrum of adverse effects. More recently, reports documenting resistance against various antiectoparasite drugs, complicated and severe courses of the diseases, and adverse effects of drug therapy have prompted the development of new treatment strategies and drugs for optimal disease management. Because the strategies currently recommended for the treatment of ectoparasites differ worldwide, this review proposes a rational approach to selecting the best therapeutic agent by comparing the pharmacokinetics, pharmacodynamics, drug efficacy and adverse effects. A literature search of the currently Internet accessible libraries PubMed, Medline and Ideal library, of citations of articles found there, and from communications with the Federal Institute for Drugs and Medical Devices, Germany, was conducted based on this approach. One major observation of this literature search is that permethrin is the treatment of choice for lice and scabies in the US and in Great Britain, whereas lindane is still recommended for scabies in most other European countries because of its longer-standing record of effectiveness. Although permethrin has not yet been proven to be more effective than lindane in treating infections with these ectoparasites, it currently appears to have the best efficacy versus safety profile of topical treatments for scabies and lice. Ivermectin is a newer oral drug for the treatment of ectoparasites, which has been used with great success in the treatment of onchocercosis and other endoparasites. Although ivermectin appears to be a promising drug, its role in the treatment of ectoparasitic infections will be clarified as more study data become available. Finally, it is important to emphasise the clinical aspects of ectoparasite therapy and that providing the patient with optimal instructions on the use of topical therapeutics is of great importance in avoiding adverse effects and assuring complete removal of the ectoparasite, thereby avoiding the development of drug-resistance.

13-cis retinoic acid exerts its specific activity on human sebocytes through selective intracellular isomerization to all-trans retinoic acid and binding to retinoid acid receptors.

Despite its potent biologic effect on human sebocytes, 13-cis retinoic acid exhibits low binding affinity for cellular retinoic acid binding proteins and nuclear retinoid receptors. Hence, 13-cis retinoic acid may represent a pro-drug possibly acting through all-trans isomerization. In this study, marked isomerization of 13-cis retinoic acid has been confirmed in cultured SZ95 sebocytes showing 2- to 15-fold higher levels of all-trans retinoic acid at 12-72 h, as measured by high performance liquid chromatography. In contrast, only low amounts of all-trans retinoic acid were converted intracellularly to its 13-cis isoform. 9-cis retinoic acid was not detected after either 13-cis retinoic acid or all-trans retinoic acid treatment. The rapid isomerization of 13-cis retinoic acid to high levels of all-trans retinoic acid was a sebocyte-specific event, as no significant isomerization of 13-cis retinoic acid to all-trans retinoic acid occurred in HaCaT keratinocytes. De novo mRNA expression of cytochrome P450 1A1, a major xenobiotic metabolizing enzyme, in SZ95 sebocytes was induced by all-trans retinoic acid, but not by 13-cis retinoic acid. In addition, mRNA levels of cellular retinoic acid-binding protein II, which is supposed to regulate the concentration of intracellular all-trans retinoic acid, rapidly increased under all-trans retinoic acid treatment (30 min-6 h), whereas the 13-cis retinoic acid effect was markedly weaker and delayed. Both 13-cis retinoic acid and all-trans retinoic acid suppressed mRNA expression of cytochrome P450 1A2. In parallel experiments, 13-cis retinoic acid significantly reduced SZ95 sebocyte proliferation at 10-7 M, show- ing 30-40% inhibition after 9 d. All-trans retinoic acid and 9-cis retinoic acid exhibited similar anti-proliferative effects. AGN 193109, a pan-antagonist of the retinoic acid receptors, antagonized the anti-proliferative activity of all retinoic acid isomers tested in a concentration-dependent manner with complete abolishment at ratios of 1:10 13-cis retinoic acid and 1:1 all-trans retinoic acid. Coincubation of SZ95 sebocytes with 13-cis retinoic acid and AGN 193109 did not alter the intracellular concentration of 13-cis retinoic acid and its isomerization profile. In contrast, the retinoid X receptor antagonist CD 3507 did not affect the inhibition of SZ95 sebocyte proliferation induced by retinoic acids. Our findings indicate: (i) a selective 13-cis retinoic acid isomerization to all-trans retinoic acid in the intracellular compartment of SZ95 sebocytes; (ii) a reduced all-trans retinoic acid inactivation process after 13-cis retinoic acid treatment as compared with treatment with all-trans retinoic acid; and (iii) a retinoic acid receptor-mediated inhibition of SZ95 sebocyte proliferation. These data explain the sebocyte-specific activity of 13-cis retinoic acid and support a pro-drug/drug relation between 13-cis retinoic acid and all-trans retinoic acid.

Important drug interactions in dermatology.

Drug interactions can occur at any step from absorption to elimination of a drug, and can induce adverse as well as beneficial effects. Since systemic drugs are increasingly available and important in the treatment of dermatological diseases, a variety of possible interactions between concomitantly administered drugs have to be considered by dermatologists. The xenobiotic-metabolising enzyme system cytochrome P450 (CYP) is involved in the metabolism of many drugs, regulating their plasma concentrations and activities. Furthermore, the adverse effects of many drugs depend on the basal activity and inducibility of particular CYP isoenzymes in an individual patient. Since drug therapy in dermatological practice is of increasing complexity, and an increasing number of potent systemic drugs have become commonly used therapeutic agents, this review focuses on the following topics with the aim of optimising dermatological drug therapy. In the first section, all the different types of drug interactions that can occur through pharmacokinetic and pharmacodynamic mechanisms are introduced briefly, and then discussed systematically with special reference to drugs important for dermatologists. Then, the network of drug interactions that may occur from absorption to elimination is presented. The most important drug interactions mediated by CYP isoenzymes are listed. Finally, the importance of pharmacogenetics for the development of new drugs and its potential impact on the optimisation of individual therapy regimens is discussed.

Vitamin D3 and its synthetic analogue secocholestra-trien-1,2, 24-triol influence the metabolism and the isomerization of retinoic acid in human keratinocytes.

Vitamin D and vitamin A acid share metabolic pathways thereby influencing their benefit as a given drug. Little is known concerning their metabolic interactions in epidermal cells. We compared the influence of 1,25-dihydroxycholecalciferol (vitamin D3 - VD3) and its synthetic analogue secocholestra-trien-1,3,24-triol (tacalcitol - TAC) in combination with different calcium concentrations (Ca) on the metabolism and the isomerization of retinoic acid (RA) in cultured primary human keratinocytes. After preincubation with 0.09, 0.6 and 1.2 mM Ca for 24 h, followed by the addition of 10(-6), 10(-8) or 10(-10) M VD3 or TAC, we added 10(-5) M 13-cis-RA (isotretinoin). 24 h later, concentrations of RA isomers and oxidated RA metabolites were measured by RP-HPLC. VD3 (10(-6) M) inhibited the isomerization of 13-cis-RA to all-trans-RA (tretinoin) and 9-cis-RA independently from the Ca concentration in the culture medium. 10(-6)-10(-10) M TAC equally inhibit the 4-hydroxylation of all-trans-RA significantly (12.8 vs. 6.7% of total RA), thereby reducing the amount of irreversible inactivated 4-oxo-all-trans-RA, leading to a higher persistence of all-trans-RA, the active hormone. Both VD3 and its analogue TAC influence the metabolism of RA, a well-known regulator of epithelial cell proliferation and differentiation processes, in two distinct ways. Further studies are necessary to test the hypothesis that the hormone activity of RA can be increased by concomitant treatment with VD3 which prolongs the persistence of 13-cis-RA, and TAC elevating the intracellular concentration of all-trans-RA.