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Von Zeit zu Zeit wird man mit Pressemeldungen konfrontiert, die besagen, dass jemand unter der Behandlung mit Retinoiden depressiv wurde oder gar Selbstmord begangen habe. Ein typisches Beispiel wurde Anfang 2002 berichtet. Ein 15-Jahriger raste mit einem gestohlenen Flugzeug in ein Bankhochhaus in Florida. Die Polizei vermutete, er habe aus Sympathie mit Bin Laden so gehandelt. Wenige Tage spater berichteten die Medien, dass der 15-jahrige Charles Bishop das Medikament Accutane® zur Behandlung von Akne genommen habe und moglicherweise dadurch depressiv geworden sei. Solche Meldungen verunsichern Patienten und Arzt gleichermasen. Gibt es einen Zusammenhang zwischen der Einnahme von Retinoiden und Depression?

Uber lange Jahrzehnte galt der menschliche Magen wegen seines sauren Milieus als ein unwirtliches und ungeeignetes Terrain fur eine bakterielle Besiedelung.

• Compared with the antipsoriatic retinoid etretinate, the new aromatic retinoid acitretin represents an important advance due to its rapid elimination kinetics. Since in psoriasis vulgaris retinoids are used predominantly in combination regimens, we investigated the therapeutic efficacy of acitretin and UV-B compared with placebo and UV-B in a double-blind, randomized multicenter trial in 82 patients with severe psoriasis. They were treated with 35 mg of the study medication during the first 4 weeks of therapy and 25 mg thereafter, concomitantly with UV-B irradiation in increasing energy doses. Forty patients who underwent therapy with acitretin and UV-B and 38 patients who underwent therapy with placebo and UV-B were evaluated for efficacy. The target variables—psoriasis severity index and total UV-B dose—were reported at intervals of 2 weeks over a maximum period of 8 weeks. At the end of treatment, the psoriasis severity index decrease was 79% in the acitretin and UV-B group and 35% in the placebo and UV-B group. The response rate, defined as greater than or equal to a 75% decrease of the psoriasis severity index, was 60% for the combination treatment and only 24% for the control treatment. This treatment response was achieved with markedly lower cumulative UV-B energy. The median cumulative UV-B energy applied to reach 75% clinical improvement was 11.8 J/cm 2 vs 6.9 J/ cm 2 . Side effects showed a similar pattern in both groups. Our data show that the acitretin dramatically improves the results of UV-B treatment in patients with severe psoriasis. In addition, it markedly decreases the effective cumulative UV-B dose, thereby reducing the potential long-term hazards of UV irradiation. We conclude that the acitretin plus UV-B combination treatment represents a highly effective therapeutic regimen in severe psoriasis. ( Arch Dermatol . 1990;126:482-486)

A sodium dodecylsulfate-polyacrylamide electrophoretic method, which in contrast to other biochemical procedures, e.g. differential salt precipitation or ion exchange chromatography and molecular sieve chromatography, is applicable to smallest amounts of protein, is shown to be suitable for the determination of the collagen types from small skin samples, such as routine skin biopsies. After urea extraction, the tissue samples are cleaved with cyanogen bromide. The resulting CNBr peptides derived from the different alpha-chains are resolved in 12% SDS-polyacrylamide gels. Densitometric profiles of the gel electrophoretic patterns correspond to the collagen type content of the tissue specimens. Comparing fetal to adult skin, the higher content of type III collagen in the case of fetal skin can be demonstrated.

An in vitro study of the conversion of procollagen to collagen was carried out by culturing embryonic chicken calvaria and labeling them with [3,4-3H]proline and [35S]cysteine. A pulse experiment in the presence of α,α'-dipyridyl, an iron chelator, was used to accumulate procollagen in the tissue. The presence of procollagen was demonstrated by the incorporation of [35S]cysteine and by its chromatographic behavior on CM-cellulose under denaturing conditions. Using a parallel sample for a subsequent chase experiment in the absence of α,α'-dipyridyl, only traces of procollagen were found in the tissue, since [35S]cysteine had disappeared and radioactive material chromatographed with the authentic α chains of lathyritic rat skin collagen. It is proposed that the conversion of procollagen to collagen is paralleled by the release of procollagen peptides into the culture medium, indicating a single step enzymatic cleavage. These peptides were isolated from the culture medium, and their molecular weights were determined as 18,000 for a [35S]cysteine-containing and 12,000 for a [35S]cysteine-free peptide. Both values are within the size range expected for peptides cleaved from procollagen chains of molecular weights between 110,000 and 120,000.

The collagen in localized and systemic scleroderma skin was studied by light microscopy with silver impregnation (50 patients), electron microscopy (14 patients), and immunofluorescence microscopy using specific antibodies against Type I and Type III collagens (12 patients). In the cellular stage, the dermis and adipose tissue revealed perivascular or diffuse cellular infiltrates (mostly lymphocytes, plasma cells, and macrophages), accompanied by deposition of Type III collagen. The lower dermis also showed an increase in Type III collagen. In the fibrotic stage, the papillary layer showed a reduction and/or clumping of Type III collagen as compared to normal skin. The lower dermis and the adipose tissue revealed compact collagen consisting exclusively of Type I collagen or a mixture of Type I and Type III collagen. The pattern of Type III collagen distribution was similar to that of reticulin, thus suggesting that at least some reticulin fibrils may represent Type III collagen.

The collagen type composition of normal and pathologic scars was examined in comparison with normal skin from the same individual. Particular care was taken to separate scar tissue from adjacent normal dermis. After urea extraction, the tissue specimens were cleaved with cyanogen bromide. The presence of the dermal collagen types I and III was deduced from the electrophoretic distribution patterns of the CNBr peptides in 12% SDS-polyacrylamide gels. The intensity of the type III specific peptide bands correlates with the type III content of the samples. Using this method, the presence of both type I and type III collagen can be proved in normal as well as pathologic scars. The type III content in older normal scars is slightly increased, whereas the type III content of pathologic scars is significantly increased in comparison with the type III content of normal skin. The electrophoretic CNBr peptide distribution pattern of pathologic scar tissue is almost the same as that of fetal skin. Both are clearly different from the peptide pattern of normal adult skin.

The human dermis consists of two morphologically different layers. A loose meshwork of thin collagenous fibres is characteristic for the adventitial dermis with includes the papillary and the periadnexal dermis. Thick, coarse collagen bundles are the main feature of the reticular dermis. Two different collagens, type I and type III occur in the dermis as shown previously by biochemical analyses. Antibodies specific for type I collagen or type III collagen and their corresponding precursors were used in indirect immunofluorescence tests to localize the various collagens in frozen sections of normal adult skin. Whereas type I collagen is found in all dermal layers, the main part of type III collagen can be found within the adventitial dermis. Antibodies against the precursor of type I collagen stain only a bandlike region immediately beneath the epidermis. Antibodies against the precursor of type III collagen stain the same regions as antibodies against the helical part of type III collagen.

The nature of collagen from 2 cases of dermatofibrosarcoma protuberans was studied. For this purpose, the tumor tissue was carefully separated from adjacent normal dermis. The collagen types comprised in the tumor were identified by CM-cellulose chromatographic and SDS-gel electrophoretic analysis of the component alpha-chains. Semiquantitative evaluation of the relative type III content was established by separation of the cyanogen bromide peptides on gels of 12% polyacrylamide in SDS. These studies showed that dermatofibrosarcoma protuberans contains alpha 1(I)-, alpha 2-, and alpha 1(III)-chains as well, and corresponding type I- and type III-related CNBr peptides. Comparing the collagen from dermatofibrosarcoma protuberans to that of normal skin, the relatively increased type III content in the case of dermatofibrosarcoma protuberans becomes apparent.

Mit der Entdeckung der Sulfonamide und des Penizillins durch Domagk bzw. Fleming in den 30er Jahren dieses Jahrhunderts war zum ersten Mal die Moglichkeit gegeben, mit Substanzen, die selektiv die Zellen niedriger Lebewesen schadigten und fur den Menschen weitgehend atoxisch waren, Bakterien wirksam auch innerhalb des Organismus zu bekampfen. Schon wenige Jahre nach Einfuhrung der Sulfonamide und des Penizillins entwickelte sich jedoch bei einigen vorher gut auf die Behandlung ansprechenden Keimarten eine zunehmende Antibiotika-Resistenz, wobei vor allem die Penizillinresistenz zu nennen ist, welche die Bekampfung des Staphylokokkenhospitalismus der 50er Jahre sehr schwierig gestaltete.

Antibodies against two types of species specific determinants, designated P and S, can be differentiated in rabbit antisera against acid soluble calf skin collagen. Using the passive hemagglutination inhibition technique, they were localized with collagen α-chains, with peptides obtained by treatment of the α-chains with cyanogen bromide and with fragments isolated from collagenolytic digests of native collagen. The P-determinant is labile to proteolytic attack (pronase, chymotrypsin, pepsin). It was detected in a 300 A region at the C-terminus of both types of α-chains. The S-determinant is resistant to proteases and was found to occur in an interior region of the α2-chain. The serological activity is contained in one of the collagenolytic peptides.