[Retinoids in dermatopharmacology]. / Retinoide in der Dermatopharmakologie.

BACKGROUND: Retinoids are important in regulating cell proliferation and differentiation and play an important role in the body, including the skin. OBJECTIVES: Our objective is to review the current medical literature regarding use, effects and side-effects of topical and systemic retinoids used for therapy. METHODS: Pubmed/Medline electronic database was searched for relevant German and English literature. RESULTS: The group of retinoids used for therapeutic purposes includes both naturally occurring and chemically synthesized vitamin A derivates. Because of their influence on keratinization and epithelial differentiation, as well on the proliferation of benign and malignant keratinocytes, retinoids have found a wide application in the field of dermatopharmacology. CONCLUSION: Retinoids are among the most efficacious drugs used in the treatment of dermatological disorders and have a wide range of biological effects. Thorough knowledge about side-effects and comprehensive information for the patient are essential for safe treatment with retinoids.

[Morbihan disease as a special form of rosacea: review of pathogenesis and new therapeutic options]. / Morbus Morbihan als Sonderform der Rosazea: Einblick in die Pathogenese und neue Therapieoptionen.

Morbihan disease is classified as a special form of rosacea, which presents with persistent facial erythema and solid edema because of marked involvement of the lymphatic vessels. The cheeks, nose and forehead are particularly affected. Currently, the treatment options of this cosmetically very disturbing disease are limited. However, every attempt should be made to provide treatment because of the great emotional suffering of the patients. We review some new currently available therapeutic options for Morbihan disease. In our patient, we were able to achieve a significant improvement with systemic isotretinoin 30 mg/day over a period of 12 months.

Dexpanthenol modulates gene expression in skin wound healing in vivo.

Topical application of dexpanthenol is widely used in clinical practice for the improvement of wound healing. Previous in vitro experiments identified a stimulatory effect of pantothenate on migration, proliferation and gene regulation in cultured human dermal fibroblasts. To correlate these in vitro findings with the more complex in vivo situation of wound healing, a clinical trial was performed in which the dexpanthenol-induced gene expression profile in punch biopsies of previously injured and dexpanthenol-treated skin in comparison to placebo-treated skin was analyzed at the molecular level by Affymetrix® GeneChip analysis. Upregulation of IL-6, IL-1ß, CYP1B1, CXCL1, CCL18 and KAP 4-2 gene expression and downregulation of psorasin mRNA and protein expression were identified in samples treated topically with dexpanthenol. This in vivo study might provide new insight into the molecular mechanisms responsible for the effect of dexpanthenol in wound healing and shows strong correlations to previous in vitro data using cultured dermal fibroblasts.

Ultraviolet B radiation and reactive oxygen species modulate interleukin-31 expression in T lymphocytes, monocytes and dendritic cells.

BACKGROUND: Interleukin (IL)-31 is a novel Th2 T-cell cytokine that induces pruritus and dermatitis in transgenic mice. While enhanced mRNA expression of this cytokine is detected in skin samples of inflammatory skin diseases, the regulation of IL-31 expression is poorly understood. OBJECTIVES: To assess the effects of ultraviolet (UV) B radiation and H2O2 on IL-31 mRNA and protein expression in skin and different peripheral blood mononuclear cells (PBMCs). METHODS: The effects of UVB radiation and H2O2, as a prototypic reactive oxygen species, on IL-31 mRNA and protein expression were analysed in various inflammation-related cells and murine skin tissue. RESULTSTreatment of cells with UVB radiation and H2 O2 strongly induced IL-31 mRNA and protein expression in human PBMCs and in the skin of SKH-1 mice. Following exposure to UVB or H2O2, we observed increased expression of IL-31 mRNA in T cells, monocytes, macrophages, and immature and especially mature dendritic cells. H2O2 treatment but not UVB radiation led to a moderate upregulation of IL-31 mRNA expression in epidermal keratinocytes and dermal fibroblasts. Pretreatment of T lymphocytes with the MAPK p38 inhibitor SB203580 or the MEK1 inhibitor U0126 reduced the stimulatory effect of H2O2. These experiments suggest that p38 is involved in the regulation of IL-31 expression in human skin. CONCLUSIONS: Our studies reveal that UVB and reactive oxygen species stimulate the expression of IL-31 in PBMCs and skin, especially in T cells, monocytes and monocyte-derived dendritic cells.

Tacrolimus modulates dendritic cell activation in the sensitization phase of allergic contact dermatitis.

BACKGROUND: Knowledge of the effect of topically applied calcineurin antagonists such as tacrolimus on the sensitization phase of allergic contact dermatitis is currently limited. OBJECTIVE: To investigate tacrolimus-dependent immunomodulation on gene expression alterations in human antigen-presenting cells which are stimulated with small-molecular-weight contact allergens. METHODS: Monocyte-derived dendritic cells (moDC) and THP-1 cells were stimulated with the contact sensitizer cinnamic aldehyde (CAld) and compared with the very strong experimental sensitizer 2,4,6-trinitrobenzene sulfonic acid (TNBS) in vitro. Quantitative PCR analysis was used to detect gene expression changes, particularly of interleukin (IL) 8, as an indicator of differential dendritic cell (DC) gene expression after sensitizer stimulation in the absence or presence of tacrolimus and betamethasone at two different concentrations. RESULTS: DC activation was clearly demonstrated by a significant IL-8 upregulation after 24 h, whereas tacrolimus or betamethasone alone did not affect IL-8 baseline expression. Betamethasone and, to a lesser extent, tacrolimus led to a marked reduction of chemical-induced IL-8 expression by TNBS and CAld. CONCLUSION: The results of the present study support the hypothesis that the calcineurin inhibitor tacrolimus has modulatory effects on human antigen-presenting cells during the sensitization phase of allergic contact dermatitis. In addition, moDC as well as THP-1 cells may serve as a system to study immune-modulating effects of drugs such as glucocorticoids or calcineurin antagonists.

Soluble immune receptor serum levels are associated with age, but not with clinical phenotype or disease severity in childhood atopic dermatitis.

BACKGROUND: Soluble immune receptors (SIRs) have been proposed as biomarkers in patients with atopic dermatitis (AD). However, their clinical applicability in affected children has rarely been studied. OBJECTIVE: To assess the diagnostic usefulness of serum SIRs in childhood AD by correlating the obtained receptor profiles with serological parameters and clinical features such as age, AD phenotype and disease severity. METHODS: We investigated 100 children with AD. The sCD14, sCD23, sCD25, sCD30, total IgE (tIgE) and eosinophilic cationic protein (ECP) were determined using sera of all children. The clinical phenotype was classified as extrinsic AD (ADe) or intrinsic AD (ADi) by the presence of allergen-specific IgE antibodies. RESULTS: A total of 55 male and 45 female children were recruited. The sCD23, sCD25 and sCD30 serum levels revealed significant age-dependency. At a mean SCORAD of 40 (range 8-98), none of the evaluated SIRs was correlated to disease severity. In all, 73% of patients suffered from ADe while 27% showed the ADi phenotype. None of the analysed SIRs differed significantly between ADe and ADi patients, while tIgE and ECP levels were elevated in the ADe subgroup. CONCLUSION: The current study provides evidence that sCD23, sCD25 and sCD30 serum levels are highly age-dependent. Serum concentrations of all investigated SIRs did not significantly correlate with disease severity in children with AD and were not differentially expressed in patients of different AD phenotypes. Therefore, we believe that the studied SIRs cannot be regarded as clinically useful biomarkers for the assessment of childhood AD.

[Anaphylaxis in childhood and adolescence]. / Anaphylaxie im Kindes- und Jugendalter.

Anaphylaxis represents a severe, systemic and potentially fatal hypersensitivity reaction that severely impairs the life of affected children and their caregivers. With an estimated life time prevalence of 0.05% to 2%, it is not a rare disease. Therefore every physician caring for children at risk for anaphylaxis should be familiar with this disease pattern. Foods are the most frequent triggers in children; less frequent causes include drugs and insect venom. Particularly in case of idiopathic anaphylaxis, systemic mastocytosis should be ruled out as a potential differential diagnosis in this age group as well. First line emergency treatment consists of parenteral epinephrine in a weight-adjusted dosage, and after cardiovascular stabilization systemic antihistamines and corticosteroids as well as inhaled beta-mimetics can be administered. Affected patients, their relatives and other caregivers should receive extensive training in order to guarantee an adequate emergency management of anaphylactic children.

Physician assessment of stroke risk in hypertensive patients in the Middle East and Africa: results of the action survey.

OBJECTIVES: In the absence of reliable, contemporary national data, the ACTION survey was designed to: a) provide preliminary data on stroke risk in the MEA (Middle East and Africa); b) describe the contribution of specific cardiovascular risk factors; 3) assess blood pressure (BP) control. DESIGN AND PATIENTS: This was a multi-center observational study in nine countries in the MEA region. From 2003 to 2005, 562 physicians from a variety of specialties recorded observations of cardiovascular risk factors in 4,747 hypertensive patients, aged 54-80 years. The 10-year absolute stroke risk was calculated using a scoring system based on the Framingham Heart Study observations, and comparisons made with an age-matched cohort. RESULTS: The mean 10-year stroke risk was estimated at 22.7% and was significantly higher for men (25.4%) than for women (19.5%) (P < .001) and for diabetics (28.2%) than for non-diabetics (19.4%) (P < .001). Compared with an age-matched Framingham cohort, the estimated stroke risk in our population was almost double, and was significantly higher for females (212%) than for males (192%) (P < .001). Hypertension, diabetes, left ventricular hypertrophy, and smoking were major contributing risk factors, as were physical inactivity and elevated cholesterol. Blood pressure was controlled in only 18% of the population and in 12% of diabetics. CONCLUSION: Physicians of all specialties were willing to participate in stroke risk assessment. The risk of stroke in hypertensive patients in the MEA region is high, and is higher than would be predicted using Framingham data, particularly for females. Hypertension appears to be poorly controlled in more than 80% of hypertensive patients in the MEA region.

Treatment of radiation-relapsing primary cutaneous B-cell lymphoma with an anti-CD20 monoclonal antibody.

Primary cutaneous B cell lymphomas have a high recurrence rate after treatment with surgery and/or local radiation therapy. Two men are described in whom radiotherapy-relapsing cutaneous B-cell lymphomas were successfully treated with the monoclonal anti-CD20 antibody rituximab. Both patients had a complete response with no recurrence at follow-up at 17 and 24 months for the large B-cell lymphoma of the leg and the follicle centre cell lymphoma, respectively. These are two of the few cases in the literature showing that rituximab is an effective and well-tolerated treatment for radiotherapy-relapsing primary cutaneous B cell lymphoma.

[The effect of low molecular weight substances on the human skin. Molecular mechanisms and their consequences]. / Die Wirkung kleinmolekularer Substanzen auf die menschliche Haut. Molekulare Mechanismen und Konsequenzen.

Interactions between low molecular weight compounds with cells of the skin result in reactions with different proteins which enable the uptake, metabolism and efflux of these compounds. It is unlikely, that small molecular weight compounds can achieve pharmacological concentrations within cells by diffusion alone. The pattern of influx proteins of keratinocytes is different from that of hepatocytes. If the balance between these systems is disturbed, the skin may become unable to function as a protective organ which can result in diseases including cancer or-more frequently-allergic contact dermatitis. Recent investigations of the sensitization to fragrances and p-phenylenediamine are discussed. An improved understanding of the metabolism of low molecular weight compounds can lead to new therapeutic strategies. One example is the introduction of photodynamic therapy with topical applied porphyrin precursors.

Current and future directions in the treatment of metastatic malignant melanoma.

Recently treatment strategies in advanced malignant melanoma have significantly changed. Due to high response rates (e.g. more than 50% for the Dartmouth-regimen), combination chemotherapy has been the standard therapy in several oncological and dermatooncological centers in the USA and Europe. For the last three years different prospective randomized phase III trials failed to achieve similar results. There was no benefit in overall survival and in response duration in comparison to single agent chemotherapy. Currently, randomized clinical trials seem to be the best approach for the clinical treatment of metastatic melanoma. In this review several novel strategies against malignant melanoma are discussed with focus on the role of single agent chemotherapy and biochemotherapy.

GAF film dosimetry of a tandem positioned beta-emitting intravascular brachytherapy source train.

Coronary artery brachytherapy may require treatment of lesions longer than a single source length. A treatment option is tandem positioning of the single source. This study presents relative dosimetric measurements of a cardiovascular brachytherapy source and the dosimetric characteristics in the junction region of tandem treatments. Measurements were carried out using a Novoste Beta Cath 90Sr/90Y 40 mm beta source in a plastic water phantom. Radiochromic MD-55-2 film, calibrated using both 6 MV photon and 6 MeV electron beams from a linear accelerator, was used as the dosimeter. Dose distributions around a single source and in the junction region of tandem irradiation were measured. Measurements of the near field dose as close as 1.2 mm from the source are presented. Significant over- or underdoses in the junction region of tandem irradiation were quantified. At a radial distance of 2 mm from the longitudinal axis of the source, the dose value in the middle of the junction region, normalized to the dose at 2 mm midline single source, was about 182% for a 2-seed overlap and 16% for a 2-seed gap, respectively. Dose distributions in the junction region as a function of source overlap and radial distance have fairly high gradients and exhibit characteristic patterns. The fraction of prescription dose was found to have a sigmoidal dependence on overlap size, for radial distances ranging between 1.2 and 3 mm. The parameters of these sigmoids, quantified as functions of radial distance, could be used to provide quick and reasonable over/underdose estimates, given any potential overlap or gap in the junction area, with an uncertainty within 10%.

[Array technology in skin pharmacology and allergology]. / Arraytechnologien in der Dermatopharmazie und Allergologie.

Because of their variable application, microarrays are currently used in different areas of research and development, such as skin pharmacology and allergology. Microarrays are plane carriers, on whose surface a variety of known DNA-molecules and proteins were immobilised. Transcripts can be detected by cDNA- and oligonucleotid-arrays and proteins of activated genes can be discovered using antibody microarrays. Detection of allergen-specific IgE from human serum can be performed using allergen chips. Since many details of the molecular mechanism and pathogenesis of skin cancer and inflammatory skin diseases and the effect of xenobiotics on cells of the human skin are still not known, array-technologies are a powerful tool to identify novel marker genes and offer the possibility of develop new therapeutic strategies as well as prognosis- and diagnosis-systems.