Direct biological effects of fractional ultrapulsed CO2 laser irradiation on keratinocytes and fibroblasts in human organotypic full-thickness 3D skin models.

Molecular effects of various ablative and non-ablative laser treatments on human skin cells-especially primary effects on epidermal keratinocytes and dermal fibroblasts-are not yet fully understood. We present the first study addressing molecular effects of fractional non-sequential ultrapulsed CO2 laser treatment using a 3D skin model that allows standardized investigations of time-dependent molecular changes ex vivo. While histological examination was performed to assess morphological changes, we utilized gene expression profiling using microarray and qRT-PCR analyses to identify molecular effects of laser treatment. Irradiated models exhibited dose-dependent morphological changes resulting in an almost complete recovery of the epidermis 5 days after irradiation. On day 5 after laser injury with a laser fluence of 100 mJ/cm2, gene array analysis identified an upregulation of genes associated with tissue remodeling and wound healing (e.g., COL12A1 and FGF7), genes that are involved in the immune response (e.g., CXCL12 and CCL8) as well as members of the heat shock protein family (e.g., HSPB3). On the other hand, we detected a downregulation of matrix metalloproteinases (e.g., MMP3), differentiation markers (e.g., LOR and S100A7), and the pro-inflammatory cytokine IL1α.Overall, our findings substantiate the understanding of time-dependent molecular changes after CO2 laser treatment. The utilized 3D skin model system proved to be a reliable, accurate, and reproducible tool to explore the effects of various laser settings both on skin morphology and gene expression during wound healing.

Molecular effects of fractional ablative erbium:YAG laser treatment with multiple stacked pulses on standardized human three-dimensional organotypic skin models.

The molecular changes in gene expression following ablative laser treatment of skin lesions, such as atrophic scars and UV-damaged skin, are not completely understood. A standardized in vitro model of human skin, to study the effects of laser treatment on human skin, has been recently developed. Therefore, the aim of the investigation was to examine morphological and molecular changes caused by fractional ablative erbium:YAG laser treatment on an in vitro full-thickness 3D standardized organotypic model of human skin. A fractional ablative erbium:YAG laser was used to irradiate organotypic human 3D models. Laser treatments were performed at four different settings using a variety of stacked pulses with similar cumulative total energy fluence (60 J/cm2). Specimens were harvested at specified time points and real-time PCR (qRT-PCR) and microarray studies were performed. Frozen sections were examined histologically. Three days after erbium:YAG laser treatment, a significantly increased mRNA expression of matrix metalloproteinases and their inhibitors (MMP1, MMP2, MMP3, TIMP1, and TIMP2), chemokines (CXCL1, CXCL2, CXCL5, and CXCL6), and cytokines such as IL6, IL8, and IL24 could be detected. qRT-PCR studies confirmed the enhanced mRNA expression of IL6, IL8, IL24, CXCLs, and MMPs. In contrast, the mRNA expression of epidermal differentiation markers, such as keratin-associated protein 4, filaggrin, filaggrin 2, and loricrin, and antimicrobial peptides (S100A7A, S100A9, and S100A12) as well as CASP14, DSG2, IL18, and IL36ß was reduced. Four different settings with similar cumulative doses have been tested (N10%, C10%, E10%, and W25%). These laser treatments resulted in different morphological changes and effects on gene regulations. Longer pulse durations (1000 µs) especially had the strongest impact on gene expression and resulted in an upregulation of genes, such as collagen-1A2, collagen-5A2, and collagen-6A2, as well as FGF2. Histologically, all treatment settings resulted in a complete regeneration of the epidermis 3 days after irradiation. Fractional ablative erbium:YAG laser treatment with a pulse stacking technique resulted in histological alterations and shifts in the expression of various genes related to epidermal differentiation, inflammation, and dermal remodeling depending on the treatment setting applied. A standardized in vitro 3D model of human skin proved to be a useful tool for exploring the effects of various laser settings both on skin morphology and gene expression during wound healing. It provides novel data on the gene expression and microscopic architecture of the exposed skin. This may enhance our understanding of laser treatment at a molecular level.

[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.

[Pemphigus erythematosus]. / Pemphigus erythematosus mit Übergang in einen Pemphigus foliaceus.

Pemphigus erythematosus, also known as Senear-Usher syndrome, was originally described as a variant of pemphigus with features of lupus erythematosus but regarded today as a localized form of pemphigus foliaceus and considered an autoimmune bullous disease. The autoantigen is desmoglein 1, a desmosomal adhesion protein in keratinocytes. A 69-year-old man presented with a 3-month history of erosions and blisters on the cheeks, which then also appeared on the trunk. Clinical and histopathologic criteria as well as immunofluorescence studies lead to the diagnosis of pemphigus erythematosus with transition to pemphigus foliaceus.

[Iodine allergy]. / Jodallergie.

We report on a patient with an iodine allergy. He developed a delayed cutaneous reaction after receiving an iodinated radiographic contrast media and at the same time topical disinfection with povidone-iodine. In the patch- and intradermal tests he showed positive results with various radiographic contrast media, povidone- iodine and iodine, but not with povidone.

[Lymphomatoid papulosis in a 2 1/2-year-old boy]. / Lymphomatoide Papulose bei einem 2 1/2-jährigen Jungen.

Lymphomatoid papulosis (LyP) is a rare cutaneous lymphoproliferative disorder that has malignant histologic features and a benign clinical course. LyP is classified according to the WHO/EORTC classification for cutaneous lymphoma as a CD30-positive lymphoproliferative disorder. Few previous reports have detailed features of LyP in pediatric and adolescent patients, but LyP very rarely presents in early childhood. A 2 1/2-year-old boy presented with a 1-year history of recurrent papular and nodular lesions on the face and trunk. Clinical and histopathologic criteria lead to the diagnosis lymphomatoid papulosis.

Regulation of gene expression by retinoids.

Vitamin A serves as substrate for the biosynthesis of several derivates (retinoids) which are important for cell growth and cell differentiation as well as for vision. Retinoic acid is the major physiologically active form of vitamin A regulating the expression of different genes. At present, hundreds of genes are known to be regulated by retinoic acid. This regulation is very complex and is, in turn, regulated on many levels. To date, two families of retinoid nuclear receptors have been identified: retinoic acid receptors and retinoid X receptors, which are members of the steroid hormone receptor superfamily of ligand-activated transcription factors. In order to regulate gene expression, all-trans retinal needs to be oxidized to retinoic acid. All-trans retinal, in turn, can be produced during oxidation of all-trans retinol or in a retinol-independent metabolic pathway through cleavage of ß-carotene with all-trans retinal as an intermediate metabolite. Recently it has been shown that not only retinoic acid is an active form of vitamin A, but also that all-trans retinal can play an important role in gene regulation. In this review we comprehensively summarize recent literature on regulation of gene expression by retinoids, biochemistry of retinoid receptors, and molecular mechanisms of retinoid-mediated effects on gene regulation.