Hans Meffert

Determination of the horny layer profile by tape stripping in combination with optical spectroscopy in the visible range as a prerequisite to quantify percutaneous absorption

A new method was developed to determine the horny layer profile of volunteers using tape stripping in combination with UV/visible spectroscopy. The optical absorbance and the weight of corneocyte aggregates were compared as parameters for the determination of the mass of the horny layer particles fixed to the individual tapes. It was shown that the potential disturbances influencing both parameters must be considered critically before calculating the correlation factor, found as R2mean = 0.93 ± 0.05. It was proven that the absorbance in the visible range is better suited than the weight to quantify the amount of corneocyte aggregates removed by a single strip. The new method allows an exact anatomical localization of the individual tapes and all data obtained within the depth profile of the stratum corneum. This was exemplified by the determination of the penetration of chemical and physical UV filters into the horny layer.

High-dose UVA1 therapy for atopic dermatitis: Results of a multicenter trial

BACKGROUND The results of an open, single-center study suggested that phototherapy with high doses of UVA1 radiation (UVA1R; 340-400 nm) is effective for acute, severe exacerbations of atopic dermatitis (AD). OBJECTIVE The purpose of this study was to assess the effectiveness of high-dose UVA1 phototherapy for acute, severe AD in a randomized multicenter trial in direct comparison with topical glucocorticoid therapy. METHODS Patients were treated with high-dose UVA1R (10 days, 130 J/cm2/day; n = 20), topically with fluocortolone (10 days, 1 x daily; n = 17), or with UVA-UVB therapy (10 days, 1 x daily, minimal erythema dose-dependent; n = 16). RESULTS With a clinical scoring system, significant differences in favor of high-dose UVA1R and fluocortolone therapy were observed (p < 0.0001), as compared with UVA-UVB therapy. At day 10, high-dose UVA1R was superior to fluocortolone (p < 0.002) therapy. Serum levels of eosinophil cationic protein and the blood eosinophil count were significantly reduced after high-dose UVA1 or fluocortolone, but not UVA-UVB therapy. CONCLUSION This study confirms the therapeutic effectiveness of high-dose UVA1 monotherapy for treatment of severe exacerbations of AD.

Stable lipid peroxidation products in human skin: detection, ultraviolet light-induced increase, pathogenic importance.

Products of lipid peroxidation (malonaldehyde, Schiff-bases) were detected in human skin. These products were increased after UV-light exposition, on chronically sun-exposed areas as well as with advancing age. Malonaldehyde cross linked epidermal glucose-6-phosphate-dehydrogenase and diminished their activity.

The Influence of Haematoporphyrin Derivative and Visible Light on Murine Skin Graft Survival, Epidermal Langerhans Cells and Stimulation of the Allogeneic Mixed Leucocyte Reaction

The influence of combined photochemical treatment with a haematoporphyrin derivative and visible light on antigen‐presenting cells was evaluated. Treatment of murine skin grafts with this procedure prolonged their subsequent survival on allogeneic recipients. The haematoporphyrin derivative and light decreased the ATPase activity of epidermal Langerhans cells in murine skin. When stimulator cells in a human allogeneic mixed leucocyte reaction were treated with the haemaioporphyrin derivative and light, they lost their stimulatory capacity. It is proposed that the haemaioporphyrin derivative and visible lighl interfere, on analogy with ultraviolet radiation, with the function of antigen‐presenting cells.

Studies on the effects of a high dose UVA-1 radiation therapy on surface markers and function of epidermal Langerhans cells

Recently, high-dose UVA-1 therapy (340–400 nm) was introduced as an effective treatment of severe exacerbated atopic dermatitis. Since the target of this type of radiation in the skin is not known we investigated using the mouse model whether surface markers of the antigen-presenting function of epidermal Langerhans cells are affected by UVA-1 radiation. Even repeated high doses of UVA-1 radiation (up to 50 J/cm2) had no detectable effect on surface ATPase activity and Ia antigen expression on Langerhans cells. Also, the contact allergen oxazolone was presented normally in skin treated with UVA-1 radiation. In contrast, if the mice were injected 1 h before irradiation with 8-methoxypsoralen a dramatic reduction in ATPase activity and Ia antigen expression on Langerhans cells was observed and the induction of contact sensitivity was suppressed (PUVA effect). These results show that epidermal Langerhans cells are not impaired either in structure or function and that these cells probably do not represent the primary target of UVA-1 radiation in the skin. No side effects resulting from a diminished Langerhans cell function should result from high-dose UVA-1 therapy.

Prolongation of the survival of skin grafts in mice by PUVA treatment

The combined application of psoralen and UVA radiation to skin grafts induced a prolongation of the survival time of the grafts in mice. This was observed using the H-Y barrier, an allogeneic barrier without H-2 disparities, and a strong H-2 incompatible barrier. The effect is probably due to a reduction of antigen-presenting cells, or to other, unknown mechanisms.

Prolongation of skin graft survival in mice by in vitro PUVA treatment and failure of induction of specific immunological memory by PUVA-treated grafts

SummaryTreatment of murine skin grafts in vitro with 8-methoxypsoralen and longwave ultraviolet radiation prolonged their subsequent survival on allogeneic recipients, but not in cases where the recipients had been presensitized by a former skin graft of the same donor strain. In contrast to normal skin, grafts pretreated with 8-methoxypsoralen and longwave ultraviolet radiation were not able to induce an immunological memory as revealed by a second transplantation of normal skin. The results show that primary and secondary skin graft rejections can be affected by the combined action of psoralen and ultraviolet radiation.

PUVA therapy damages psoriatic and normal lymphoid cells within milliseconds

SummaryResults of previous investigations have indicated that photochemotherapy (PUVA) attacks membranes of target cells. Using the combination of a stopped-flow technique and laser irradiation we were able to prove that the fast PUVA effect is explainable solely by the membrane damage. Lymphoid cells of healthy persons or psoriatics were taken, within 1 ms mixed with 8-methoxy-psoralen (8-MOP) at concentrations of 1.0, 0.1, and 0.05 μg/ml, and then irradiated by a 337-nm laser pulse (0.5 mJ/cm2) lasting some picoseconds. Approximately 1 ms after administration of 8-MOP to the cell surface at least 10% of the cells were damaged, as could be judged using the standard trypan blue exclusion test. This happened at 8-MOP concentrations of 1.0 or 0.1 μg/ml plus laser irradiation, but a concentration of 0.05 μg/ml 8-MOP plus laser exposure did not cause any effect within 8 ms after mixing. There was no difference between using lymphoid cells from healthy persons or from psoriatics. The fact that only a very short time is necessary before cell damage occurs means that, as far as the fast PUVA effect is concerned, a photochemical reaction involving nuclear DNA can be discounted.

Untersuchungen zum Wirkungsmechanismus von Dithranol: Erhöhte Lipidperoxydation und Enzymhemmung

The results reported in connection with previously published data suggest the importance of increased lipid peroxidation in the epidermis after Dithranol treatment. Malonaldehyde, one of the main prod

Die Behandlung der Psoriasis capillitii mit Dithranol

Dithranol kann in den gebräuchlichen Fettgrundlagen am behaarten Kopf nicht angewendet werden und ist in abwaschbaren Zubereitungen zumindest in Deutschland wenig im Gebrauch. Mögliche Gründe dafür könnten sein, daß die Anwendung zu wenig bekannt ist, die Wirkung unterschätzt und Nebenwirkungen überschätzt werden. Wir haben deshalb die Fachliteratur zunächst nach Studien, dann nach Rezepturvorschlägen und Anwendungsempfehlungen und schließlich nach Berichten über Nebenwirkungen durchgesehen. Wir listen auf, welche dithranolhaltigen Fertigpräparate zur Kopfbehandlung in den europäischen Nachbarländern verfügbar sind, dazu die Empfehlungen für den Gebrauch und Warnhinweise für Nebenwirkungen.