Pathogenetic mechanisms in androgenetic alopecia are not yet fully understood; however, it is commonly accepted that androgens like testosterone (T) and 5α-dihydrotestosterone (5α-DHT) inhibit hair follicle activity with early induction of the catagen. Thus, we investigated the influence of T and 5α-DHT on proliferation, cell death and bcl-2/bax expression in cultured dermal papilla cells (DPC) from nonbalding scalp regions of healthy volunteers. T and 5α-DHT induced apoptosis in DPC in a dose-dependent and time-related manner; in addition a necrotic effect due to T at 10–5M was found. Interestingly, bcl-2 protein expression was decreased in T- and 5α-DHT-treated cells, leading to an increase in the bax/bcl-2 ratio. In addition, T and 5α-DHT induced proteolytic cleavage of caspase 8 and inhibited proliferation of DPC at 10–5M. High concentrations of T and 5α-DHT were needed to induce apoptotic effects in DPC. These data suggest that DPC from nonbalding scalp regions do have the capacity to undergo apoptosis, but need a high androgen stimulus. The present study provides an interesting new pathogenetic approach in androgenetic alopecia.

The hair follicle and its appendages are important target structures for hormones. Plasma levels, local hormone metabolism and differential receptor expression regulate hair growth and hair cycling as well as sebaceous gland function. Even minor imbalances in this system, e.g. abnormal expression of hair follicle‐associated isoenzymes, may cause clinical symptoms such as hair loss, seborrhoea or hirsutism.Conventional therapeutic strategies, which aim to control peripheral hyperandrogenism, include systemic administration of androgen inhibitors (e.g. oral contraceptives, GnRH analogues), peripheral androgen blockers (CPA, CMA, glutamide, finasteride) as well as topical application of estrogens. As our knowledge about hormone systems and their complex interactions increases, new molecules are gaining importance: rosiglitazone and metformin are compounds which increase the sensitivity to insulin, topical application of minoxidil has been shown to regulate perifollicular blood flow and vascularization, and anti‐inflammatory compounds can as well be beneficial in the treatment of androgenetic alopecia.Because such therapies are, still, rather unspecific, current research focuses on the development of individualized strategies which allow to specifically treat the various manifestations caused by hormone‐related disorders. From our perspective, the aims of future drug development are as follows.In the first place, the identification of new targets, possibly beyond sex steroids in the narrow sense is highly important. Components of the POMC‐system, for example, have been shown to regulate cell differentiation and also hair cycling.And secondly, to develop drug delivery systems, which allow to specifically directing active compounds to target structures. Such improved drug delivery may allow to reduce side‐effects and to increase the efficacy of current therapies. Studies by our group and others suggest that microparticles, due to their ability to aggregate in the hair follicle openings, are promising drug delivery systems. In fact, we recently reported that the penetration depths of transcutaneously applied microparticles into the follicular duct depends on the size of the particles and on the dimension of the hair follicle, suggesting that particle‐based drug delivery systems allow to selectively target hair follicle compartments such as the entry level of the sebaceous duct or the bulge region.

Human hair and nails, like all other organs, undergo chronological aging. Age-associated changes in growth, color, and structure of the hair and nails are common. In contrast to the aging process of the skin, the gerontobiological course of hair and nails has not been investigated comprehensively. Investigations on signaling pathways important for melanogenesis of the hair follicle improve our understanding of processes involved in hair greying. Differences in the structure and quality of the nails at an advanced age are determined mainly by age-dependent variations in lipid content of the nail plates. However, it is important to recognize age-dependent processes in hair shafts and nails and to distinguish between chronological aging and pathological changes. The possibilities to improve these aging processes have, primarily, to be seen in the field of external cosmetic procedures. Since the effect of preexisting hormonal substitution treatment has not yet been adequately investigated, it can be regarded as critical to evaluate the confirmed benefits and possible risks of such treatment either for hair or for nail quality improvement.

Haare und Nägel zeigen beim Menschen, wie die übrigen Organe, chronologische, sog. intrinsische, aber auch extrinsische Alterungsprozesse. Alterungsabhängige Veränderungen in Wachstum, Farbe und Struktur der Haare und Nägel sind häufig zu beobachten. Im Gegensatz zu Alterungsprozessen an der Haut sind die gerontobiologischen Vorgänge an Haaren und Nägeln noch nicht umfassend untersucht. Untersuchungen zu Signalwegen im Haarfollikel, die an der Melanogenese beteiligt sind, helfen, unser Verständnis über Mechanismen, die zum Ergrauen der Haare führen, zu entwickeln. Veränderungen des Lipidgehalts in Nägeln bedingen Unterschiede der Struktur und Qualität der Nägel im höheren Lebensalter. Wichtig ist es, altersgerechte Prozesse an Haaren und Nägeln zu kennen und von pathologischen Veränderungen abzugrenzen. Die Möglichkeiten der Verbesserung altersbedingter Veränderungen liegen heute noch vorwiegend auf dem Gebiet der kosmetischen, externen Behandlung. Da die Wirkung einer bereits auf dem Gebiet der Alterungsprävention praktizierten hormonellen Substitution noch nicht hinreichend untersucht ist, gilt es kritisch den nachweislichen Nutzen und mögliche Risiken einer solchen systemischen Behandlung abzuwägen.

Despite the variations of length and type of hair (vellus or terminal), the growth of human hair in all body sites is cyclic. Phases of active hair growth, or anagen, are separated by periods of quiescence, or telogen. The duration of both phases varies greatly depending on the body site. Whether hairs are in anagen/telogen at the time of hair removal is important because only anagen hairs are particularly sensible to physical insults. Photo-epilation is a technique for long-term removal of unwanted hair by thermal destruction of the hair follicle and its reproductive system (stems cells). As melanin is the main chromophor existing in hair follicles the corresponding wavelength spectrum would range from ultraviolet up to infrared light. Furthermore longer wavelengths are preferred as the cromophor lies deep in the skin and the penetration of light is increasing with the wavelength. Thus, in the range of 600-1100 nm melanin absorption may be used for selective photothermolysis of hair follicles. Yet to be resolved questions for permanent destruction are the location of the key follicular target and the possible influence of the hair growth cycle on photothermolysis-induced hair removal. An overview on the individual physiology of the hair follicle is given to discuss the latest strategies for photo-epilation.

Increased cell volume, accumulation of lipid droplets in the cytoplasm, and nuclear degeneration are phenomena indicating terminal differentiation of human sebocytes followed by holocrine secretion and cell death. The molecular pathways of natural and induced sebocyte elimination are still unknown, however. In this study, SZ95 sebocytes were found to exhibit DNA fragmentation after a 6 h culture followed by increased lactate dehydrogenase release after 24 h, indicating cell damage. With the help of morphologic studies and using Oil Red detection of cellular lipids, cell enlargement, accumulation of lipid droplets in the cytoplasm, and nuclear fragmentation could be observed under treatment with arachidonic acid. Staurosporine, a potent inhibitor of phospholipid Ca2+ -dependent protein kinase, increased externalized phosphatidylserine levels on SZ95 sebocytes, detected by annexin V/propidium iodide flow cytometry, as early as after 1 h, whereas dose-dependent reduction of bcl-2 mRNA and protein expression, enhanced DNA fragmentation, and increased caspase 3 levels, detected by caspase 3 inhibitor/propidium iodide flow cytometry, were found after 6 h of treatment. SZ95 sebocyte death was detected as early as after 6 h of SZ95 sebocyte treatment with high staurosporine concentrations (10(-6) -10(-5) M). 5alpha-Dihydrotestosterone (10(-8) -10(-5) M) did not affect externalized phosphatidylserine levels and DNA fragmentation in SZ95 sebocytes but slightly decreased lactate dehydrogenase cell release. Neither acitretin nor 13-cis retinoic acid (10(-8) -10(-5) M) affected externalized phosphatidylserine levels, DNA fragmentation, and lactate dehydrogenase cell release, despite the increased caspase 3 levels under treatment with 13-cis retinoic acid. The combined staurosporine and 13-cis retinoic acid treatment enhanced DNA fragmentation in SZ95 sebocytes to the same magnitude as in cells only treated with staurosporine. In conclusion, SZ95 sebocytes in vitro undergo apoptosis, which can be enhanced by the terminal differentiation inductor arachidonic acid or by staurosporine and leads to cell death. 5alpha-Dihydrotestosterone inhibits SZ95 sebocyte death without involving apoptotic pathways, and retinoids did not affect the programmed death of human sebocytes. The latter result fits well with the currently reported inability of normal skin cells to undergo apoptosis after treatment with retinoids, in contrast to their malignant counterparts.

The importance of apoptosis in hair follicle cycling is still not clearly understood, however, its regulation in follicular keratinocytes (FK) during bulb regression (catagen) may be essential for hair regrowth. So far, the control of FK apoptosis remains unknown. In this study, the anti-inflammatory cytokine IL-4 was found to induce apoptosis dose and time dependently in cultured human FK, in contrast to other agents known to inhibit hair growth such as IL-1alpha, IL-1beta, TNFalpha and TGFbeta, as shown by DNA fragmentation. On the other hand, cytokines reported to be involved in hair follicle cycling including IL-4 were not able to induce apoptosis in dermal papilla cells (DPC), in contrast to staurosporine. This PKC inhibitor revealed dose-dependent apoptotic signals not only for DPC but also for FK in vitro. In further experiments the expression of apoptosis regulating proteins, possibly involved in catagen formation, was analyzed in FK and DPC. However, no striking difference in RNA expression was seen in either cell population under culture conditions and after incubation with IL-4. We conclude, therefore, that IL-4 mediated apoptosis may participate in regulating catagen formation in the hair follicle, acting selectively on cultured FK and being independent of bcl-2 and bax expression.

We report a 5-year-old boy presenting with multiple elastic type nevi and osteopoikilosis who was diagnosed as having Buschke-Ollendorff syndrome at an early age. Connective tissue lesions may present as the main symptom of varying clinical entities with different outcomes. Differential diagnosis includes papular elastorrhexis, fibroelastolytic papules of the neck, papular acne scars, and late onset focal dermal elastosis. Rare genodermatoses, i.e. Buschke-Ollendorff syndrome, pseudoxanthoma elasticum, juvenile hyaline fibromatosis and familiar cutaneous collagenoma should be carefully evaluated to provide appropriate genetic counseling and to avoid unnecessary treatment procedures.

The coexistence of vascular and pigmented nevi was first described as phakomatosis pigmentovascularis (PPV) by Ota et al. in 1947.1 Since then, about 80 cases of PPV have been reported, mainly in the Japanese literature. A patient with PPV type IIa is described, and the classification and putative pathogenesis of this disorder are reviewed.