Eva Maria Valesky

Dimethyl fumarate – only an anti‐psoriatic medication?

Fumaric acid esters have been used successfully in the therapy of psoriasis vulgaris since 1959. In the last 17 years, many of the underlying mechanisms of anti‐psoriatic action, such as a Th1/Th2 shift, a suppression of important leukocyte adhesion molecules, the induction of pro‐apoptotic pathways in T‐cells and recently anti‐angiogenic action, have been discovered. Based on the knowledge of these immunomodulatory characteristics, fumaric acid esters have been shown to be effective or potentially effective in a multitude of dermatological as well as non‐dermatological diseases. The range of new therapeutic targets reaches from multiple sclerosis to illnesses such as necrobiosis lipoidica, granuloma annulare and sarcoidosis. Experimental approaches offer promising, although preliminary, results on the treatment of cancer, malaria, chronic inflammatory lung diseases, and Huntington disease, to name but a few. This valued and well‐known drug mainly prescribed by dermatologists is now experiencing a renaissance far beyond dermatologic applications.

Bacteriological pathogen spectrum of chronic leg ulcers: Results of a multicenter trial in dermatologic wound care centers differentiated by regions

In almost every chronic wound different bacteria species can be detected.

Successful Treatment of Acrodermatitis Continua of Hallopeau with Sequential Combination of Calcipotriol and Tacrolimus Ointments

Acrodermatitis continua of Hallopeau (ACH) is a rare type of pustular psoriasis affecting the digits. We report on a 43-year-old female patient who had been suffering from ACH for more than 20 years. Despite the fact that the disease was localized on one finger during the whole period, several topical and systemic treatments resulted in only temporary or partial improvement of the lesion. Although the monotherapies with calcipotriol and tacrolimus ointments gave no satisfying results in the long-term management of the disease, the combination of both agents led to a continuous improvement of the patient’s skin condition.

Aetiology, comorbidities and cofactors of chronic leg ulcers: retrospective evaluation of 1 000 patients from 10 specialised dermatological wound care centers in Germany

Numerous comorbidities and cofactors have been known to influence wound healing processes. In this multicentre study, clinical data of 1 000 patients with chronic leg ulcers from ten specialised dermatological wound care centers were analysed. The patient cohort comprised 567 females and 433 males with an average age of 69·9 years. The wounds persisted on average for 40·8 months and had a mean size of 43·7 cm2. Venous leg ulcers represented the most common entity accounting for 51·3% of all chronic wounds, followed by mixed‐type ulcers in 12·9% and arterial ulcerations in 11·0% of the patients. Vasculitis was diagnosed in 4·5%, trauma in 3·2%, pyoderma gangrenosum in 2·8%, lymphoedema in 1·7%, neoplasia in 1·0% and delayed post‐surgical wound healing in 0·6% of the included patients. In total, 70·5% of patients suffered from arterial hypertension, 45·2% were obese, 27·2% had non‐insulin dependent diabetes, and 24·4% dyslipidaemia. Altogether 18·4% suffered from metabolic syndrome. Cofactors and comorbidities of patients with chronic leg ulcers have previously been studied but not in detail. Here, we were able to demonstrate the existence of several potentially relevant cofactors, comorbidities of their associations and geographical distributions, which should be routinely examined in patients with chronic leg ulcers and – if possible – treated.

Clinical Application of a Tissue-Cultured Skin Autograft: An Alternative for the Treatment of Non-Healing or Slowly Healing Wounds?

Background: The treatment regime of non-healing or slowly healing wounds is constantly improving. One aspect is surgical defect coverage whereby mesh grafts and keratinocyte suspension are applied. Objective: Tissue-cultured skin autografts may be an alternative for the treatment of full-thickness wounds and wounds that cover large areas of the body surface. Methods: Autologous epidermal and dermal cells were isolated, expanded in vitro and seeded on collagen-elastin scaffolds. The developed autograft was immunohistochemically characterized and subsequently transplanted onto a facial chronic ulceration of a 71-year-old patient with vulnerable atrophic skin. Results: Characterization of the skin equivalent revealed comparability to healthy human skin due to the epidermal strata, differentiation and proliferation markers. Within 138 days, the skin structure at the transplantation site closely correlated with the adjacent undisturbed skin. Conclusion: The present study demonstrates the comparability of the developed organotypic skin equivalent to healthy human skin and the versatility for clinical applications.

Development and Characterization of an Engraftable Tissue-Cultured Skin Autograft: Alternative Treatment for Severe Electrical Injuries.

Background/Aims: Optimizing the treatment regimens of extensive or nonhealing defects is a constant challenge. Tissue-cultured skin autografts may be an alternative to mesh grafts and keratinocyte suspensions that are applied during surgical defect coverage. Methods: Autologous epidermal and dermal cells were isolated, in vitro expanded and seeded on collagen-elastin scaffolds. The developed autograft was immunohistochemically and electron microscopically characterized. Subsequently, it was transplanted onto lesions of a severely burned patient. Results: Comparability of the skin equivalent to healthy human skin could be shown due to the epidermal strata, differentiation, proliferation markers and development of characteristics of a functional basal lamina. Approximately 2 weeks after skin equivalent transplantation the emerging new skin correlated closely to the adjacent normal skin. Conclusion: The present study demonstrates the comparability of the developed organotypic skin equivalent to healthy human skin and its versatility for clinical applications.

Distribution of oxytocin- and vasopressin-immunoreactive neurons in the brain of the eusocial mole rat (Fukomys anselli).

Fukomys anselli, also known as Ansells mole rat, is a subterranean, highly social (so‐called eusocial) rodent that lives in Africa. These mole rats typically form multigenerational families consisting of a single monogamous breeding pair and their nonreproductive offspring. Research on other mammals suggests that oxytocin (OT) and vasopressin (VP) as well as the distribution of OT‐ and VP‐receptors may influence social behavior and pair bonding. Recent studies on eusocial naked mole rats have shown a possible relation between sociality and OT‐immunoreactive (OT‐ir) processes. In this study, we examined expression patterns of OT and VP in the brains of F. anselli and the common Sprague‐Dawley (SD) laboratory rat. As in other species, the majority of OT‐ir and VP‐ir neurons was found in the paraventricular (Pa) and supraoptic (SO) nuclei, and scattered labeling throughout the preoptic and anterior hypothalamic areas. We found no difference in either quality or quantity of OT‐ and VP‐ir neurons between individuals of different social and reproductive ranks. Equally unexpected was the finding of specific OT‐immunoreactivity in neurons of the mammillary complex of F. anselli that was not found in SD rats. Further studies are needed to determine whether these mammillary OT‐ir neurons are causally related to monogamy in F. anselli and whether these correlates of monogamy are found in other species. Anat Rec, 2012.

Cutaneous leishmaniasis: Clinical report of two cases and review of the recent literature

With 1–1.5 million cases reported every year cutaneous leishmaniasis represents an increasing health problem. The course of cutaneous leishmaniasis varies from a single self‐healing ulcer to a persistent ulcer or progressive mucosal disease with nasopharyngeal destruction. An enormous array of topical and systemic treatment modalities has been endorsed. The response to treatment depends on the species of parasite as well as the hosts immunological and genetic status. Species‐specific treatment guidelines based on evidence from controlled studies are highly desirable. We present two cases of cutaneous leishmaniasis, one in a child and one during pregnancy, reviewing various diagnostic and therapeutic measures with special attention to problems in young and pregnant patients.

Dimethylfumarate inhibits melanoma cell proliferation via p21 and p53 induction and bcl-2 and cyclin B1 downregulation

Recent evidence suggests that dimethylfumarate (DMF), known as a highly potent anti-psoriatic agent, might have anti-tumorigenic properties in melanoma. It has recently been demonstrated that DMF inhibits melanoma proliferation by apoptosis and cell cycle inhibition and therefore inhibits melanoma metastasis. Nonetheless, the underlying mechanisms remain to be evaluated. To elucidate the effects of DMF on melanoma cell lines (A375, SK-Mel), we first performed cytotoxicity assays. No significant lactatedehydogenase (LDH) release could be found. In further analysis, we showed that DMF suppresses melanoma cell proliferation in a concentration-dependent manner. To examine whether these effects are conveyed by apoptotic mechanisms, we studied the amount of apoptotic nucleosomes and caspase 3/7 activity using ELISA analysis. Significant apoptosis was induced by DMF in both cell lines, and this could be paralleled with bcl-2 downregulation and PARP-1 cleavage. We also performed cell cycle analysis and found that DMF induced concentration-dependent arrests of G0/G1 as well as G2/M. To examine the underlying mechanisms of cell cycle arrest, we analyzed the expression profiles of important cell cycle regulator proteins such as p53, p21, cyclins A, B1, and D1, and CDKs 3, 4, and 6. Interestingly, DMF induced p53 and p21 yet inhibited cyclin B1 expression in a concentration-dependent manner. Other cell cycle regulators were not influenced by DMF. The knockdown of DMF induced p53 via siRNA led to significantly reduced apoptosis but had no influence on cell cycle arrest. We examined the adhesion of melanoma cells on lymphendothelial cells during DMF treatment and found a significant reduction in interaction. These data provide evidence that DMF inhibits melanoma proliferation by reinduction of important cell cycle inhibitors leading to a concentration-dependent G0/G1 or G2/M cell cycle arrest and induction of apoptosis via downregulation of bcl-2 and induction of p53 and PARP-1 cleavage. Hence, DMF might be an interesting agent in the treatment of melanoma and is worth further investigation in vivo.

Besondere Indikationen der Vakuumversiegelungstherapie in der Dermatochirurgie

ZusammenfassungIn den letzten Jahren hat die Vakuumversiegelung von akuten und chronischen Wunden in der Dermatochirurgie immer mehr Anhänger gefunden. Gerade bei nicht heilenden diabetischen, chronisch venösen oder auch arteriellen Ulzerationen im Fuß- und Unterschenkelbereich ist diese Technik ein fester Bestandteil der Behandlungsoptionen. Aber auch in der Versorgung von großen Exzisionswunden, beispielsweise nach der Entfernung großer Tumoren, wird die Vakuumtherapie vorzugsweise zur Induktion von Granulationsgewebe und Verkleinerung des Wunddefekts vor Spalt- oder Vollhauttransplantation oder lokaler Lappenplastik verwendet. Neben diesen allseits bekannten Anwendungsmöglichkeiten kann die Vakuumversiegelung auch für „neue“ oder seltenere Anwendungen gute Dienste leisten, von denen einige in diesem Übersichtsbeitrag dargestellt werden sollen.AbstractIn recent years negative pressure wound therapy (NPWT) has gained more and more supporters in dermatologic surgery. NPWT has become one of the standard therapeutic options, especially for non-healing diabetic, venous and arterial ulcers of the legs. When managing large wounds after tumor surgery, NPWT is frequently used to induce granulation tissue and reduce wound size before the wound is closed with split- or full-thickness skin grafts or local flaps. In addition to these well-established uses, NPWT can be also employed for a variety of “new” or rare indications, some of which are presented in this review.