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Experimental Dermatology (experimental + dermatology)
Selected AbstractsPolyamines and hair: a couple in search of perfectionEXPERIMENTAL DERMATOLOGY, Issue 9 2010Yuval Ramot Please cite this paper as: Polyamines and hair: a couple in search of perfection. Experimental Dermatology 2010; 19: 784,790. Abstract:, Polyamines (spermidine, putrescine and spermine) are multifunctional cationic amines that are indispensable for cellular proliferation; of key significance in the growth of rapidly regenerating tissues and tumors. Given that the hair follicle (HF) is one of the most highly proliferative organs in mammalian biology, it is not surprising that polyamines are crucial to HF growth. Indeed, growing (anagen) HFs show the highest activity of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis, while inhibition of ODC, using eflornithine, results in a decreased rate of excessive facial hair growth in vivo and inhibits human scalp hair growth in organ culture. In sheep, manipulation of dietary intake of polyamines also results in altered wool growth. Polyamine-containing nutraceuticals have therefore been proposed as promoters of human hair growth. Recent progress in polyamine research, coupled with renewed interest in the role of polyamines in skin biology, encourages one to revisit their potential roles in HF biology and highlights the need for a systematic evaluation of their mechanisms of action and clinical applications in the treatment of hair disorders. The present viewpoint essay outlines the key frontiers in polyamine-related hair research and defines the major open questions. Moreover, it argues that a renaissance in polyamine research in hair biology, well beyond the inhibition of ODC activity in hirsutism therapy, is important for the development of novel therapeutic strategies for the manipulation of human hair growth. Such targets could include the manipulation of polyamine biosynthesis and the topical administration of selected polyamines, such as spermidine. [source] Genetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A, MC1R and HERC2/OCA2EXPERIMENTAL DERMATOLOGY, Issue 9 2010Maider Ibarrola-Villava Please cite this paper as: Genetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A, MC1R and HERC2/OCA2. Experimental Dermatology 2010; 19: 836,844. Abstract:, The CDKN2A gene is regarded as the major familial malignant melanoma (MM) susceptibility gene. Human pigmentation is one of the main modulators of individual risk of developing MM. Therefore, the genes involved in the determination of skin colour and tanning response are potentially implicated in MM predisposition and may be useful predictors of MM risk in the general population. The human melanocortin-1 receptor gene (MC1R) plays a crucial role in pigmentation and also appears to be important in MM. The OCA2 gene has emerged as a new and significant determinant of human iris colour variation. We present a case,control study in Spanish population including 390 consecutive patients with melanoma and 254 control subjects. Sequence analysis of the entire coding region and genotyping of 5 tag-SNPs in the genomic region of MC1R was performed. We identified 27 variants, two reaching statistical significance [R160W (OR: 4.18, 95% CI: 1.24,14.04, P = 0.02) and D294H (OR: 3.10, 95% CI: 1.37,7.01, P = 0.01)] and we detected two novel non-synonymous changes: V92L and T308M. Odds ratio for carrying two functional variants was 4.25 (95% CI: 2.30,7.84, P = 3.63 × 10,6). Haplotypes of the entire MC1R region have been established, and we observed an enrichment of a rare European haplotype similar to African values carrying variants V92M and I155T. In addition, three potentially functional SNPs were selected in p16/CDKN2A and in the promoter region of OCA2/HERC2. Our data for CDKN2A gene did not reach statistically significant results for any of the two studied alleles. We found that the variant allele A > G of OCA2/HERC2 (rs12913832) was associated with pigmentation features: eye, hair and skin colour; P -values = 1.8 × 10,29, 9.2 × 10,16, 1.1 × 10,3, respectively, validating previous results. [source] Mast cell lines HMC-1 and LAD2 in comparison with mature human skin mast cells , drastically reduced levels of tryptase and chymase in mast cell linesEXPERIMENTAL DERMATOLOGY, Issue 9 2010Sven Guhl Please cite this paper as: Mast cell lines HMC-1 and LAD2 in comparison with mature human skin mast cells , drastically reduced levels of tryptase and chymase in mast cell lines. Experimental Dermatology 2010; 19: 845,847. Abstract:, To circumvent the costly isolation procedure associated with tissue mast cells (MC), two human MC lines, i.e. HMC-1 and LAD2, are frequently employed, but their relation to mature MC is unknown. Here, we quantitatively assessed their expression of MC markers in direct comparison to skin MC (sMC). sMC expressed all lineage markers at highest and HMC-1 cells at lowest levels. LAD2 cells expressed comparable high-affinity IgE receptor , (Fc,RI,) and Fc,RI, but less Fc,RI, than sMC and displayed slightly reduced, but robust Fc,RI-mediated histamine release. Only minor differences were found for total histamine content and c-Kit expression. Huge, and to this level unexpected, differences were found for MC tryptase and chymase, with sMC >>> LAD2 > HMC-1. Taken together, HMC-1 cells represent very immature malignantly transformed MC, whereas LAD2 cells can be considered intermediately differentiated. Because of the minute levels of MC proteases, MC lines can serve as surrogates of tissue MC to a limited degree only. [source] Regenerative medicine in dermatology: biomaterials, tissue engineering, stem cells, gene transfer and beyondEXPERIMENTAL DERMATOLOGY, Issue 8 2010Christina Dieckmann Please cite this paper as: Regenerative medicine in dermatology: biomaterials, tissue engineering, stem cells, gene transfer and beyond. Experimental Dermatology 2010; 19: 697,706. Abstract:, The term ,regenerative medicine' refers to a new and expanding field in biomedical research that focuses on the development of innovative therapies allowing the body to replace, restore and regenerate damaged or diseased cells, tissues and organs. It combines several technological approaches including the use of soluble molecules, biomaterials, tissue engineering, gene therapy, stem cell transplantation and the reprogramming of cell and tissue types. Because of its easy accessibility, skin is becoming an attractive model organ for regenerative medicine. Here, we review recent developments in regenerative medicine and their potential relevance for dermatology with a particular emphasis on biomaterials, tissue engineering, skin substitutes and stem cell-based therapies for skin reconstitution in patients suffering from chronic wounds and extensive burns. [source] Prostaglandin D2 production in FM55 melanoma cells is regulated by ,-melanocyte-stimulating hormone and is not related to melanin productionEXPERIMENTAL DERMATOLOGY, Issue 8 2010Mojgan Masoodi Please cite this paper as: Prostaglandin D2 production in FM55 melanoma cells is regulated by ,-melanocyte-stimulating hormone and is not related to melanin production. Experimental Dermatology 2010; 19: 751,753. Abstract:, This study shows that prostaglandins in human FM55 melanoma cells and epidermal melanocytes are produced by COX-1. Prostaglandin production in FM55 melanoma cells was unrelated to that of melanin suggesting that the two processes can occur independently. ,-Melanocyte-stimulating hormone, which had no effect on melanin production in FM55 cells, stimulated PGD2 production in these cells without affecting PGE2. While cAMP pathways may be involved in regulating PGD2 production, our results suggest that ,-MSH acts independently of cAMP, possibly by regulating the activity of lipocalin-type PGD synthase. This ,-MSH-mediated effect may be associated with its role as an immune modulator. [source] Reduction of different inflammatory cell types of the innate immune system in psoriatic skin during etanercept treatmentEXPERIMENTAL DERMATOLOGY, Issue 8 2010Marjan De Groot Please cite this paper as: Reduction of different inflammatory cell types of the innate immune system in psoriatic skin during etanercept treatment. Experimental Dermatology 2010; 19: 754,756. Abstract:, To investigate whether specific markers for innate immunity would diminish with successful treatment in psoriasis, we analyzed lesional and non-lesional skin biopsies taken from patients with moderate to severe psoriasis during 12 weeks of treatment with etanercept in correlation with the clinical response. In the clinical responders (PASI reduction >50%), all markers (CD3, CD68, CD161, elastase, BDCA-2, TNF-,) showed a decline during treatment, indicating a pivotal role for innate immunity in the pathogenesis of psoriasis. [source] Bifidobacterium longum lysate, a new ingredient for reactive skinEXPERIMENTAL DERMATOLOGY, Issue 8 2010Audrey Guéniche Please cite this paper as: Bifidobacterium longum lysate, a new ingredient for reactive skin. Experimental Dermatology 2010; 19: e1,e8. Abstract:, Reactive skin is characterized by marked sensitivity to physical (heat, cold, wind) or chemical (topically applied products) stimuli and by the impairment of the skin barrier's ability to repair itself. Several lines of evidence suggest that beyond their capacity to positively influence the composition of intestinal microbiota, some probiotic bacteria can modulate the immune system both at local and systemic levels, thereby improving immune defense mechanisms and/or down-regulating immune disorders such as allergies and intestinal inflammation. Several recent human clinical trials clearly suggest that probiotic supplementation might be beneficial to the skin. Using a probiotic lysate, Bifidobacterium longum sp. extract (BL), we demonstrated first in vitro, and then in a clinical trial, that this non-replicating bacteria form applied to the skin was able to improve sensitive skin. The effect of BL were evaluated first on two different models. Using ex vivo human skin explant model we found a statistically significant improvement versus placebo in various parameters associated with inflammation such as a decrease in vasodilation, oedema, mast cell degranulation and TNF-alpha release. Moreover, using nerve cell cultures in vitro, we showed that after 6 h of incubation in culture medium (0.3,1%), the probiotic lysate significantly inhibited capsaicin-induced CGRP release by neurones. Then, a topical cream containing the active extract was tested in a randomized, double-blind, placebo-controlled trial. Sixty-six female volunteers with reactive skin were randomly given either the cream with the bacterial extract at 10% (n = 33) or the control cream (n = 33). The volunteers applied the cream to the face, arms and legs twice a day for two months. Skin sensitivity was assessed by stinging test (lactic acid) and skin barrier recovery was evaluated by measuring trans-epidermal water loss following barrier disruption induced by repeated tape-stripping at D1, D29 and D57. The results demonstrated that the volunteers who applied the cream with bacterial extract had a significant decrease in skin sensitivity at the end of the treatment. Moreover, the treatment led to increase skin resistance against physical and chemical aggression compared to the group of volunteers who applied the control cream. Notably, the number of strippings required to disrupt skin barrier function was significantly increased for volunteers treated with the active cream. Clinical and self-assessment scores revealed a significant decrease in skin dryness after 29 days for volunteers treated with the cream containing the 10% bacterial extract. Since in vitro studies demonstrated that, on one hand, isolate sensitive neurones release less CGRP under capsaicin stimulation in the presence of the bacterial extract and, on the other hand, increased skin resistance in volunteers applying the test cream, we speculate that this new ingredient may decrease skin sensitivity by reducing neurone reactivity and neurone accessibility. The results of this studies demonstrate that this specific bacterial extract has a beneficial effect on reactive skin. These findings suggest that new approaches, based on a bacteria lysate, could be developed for the treatment and/or prevention of symptoms related to reactive skin. [source] Efficient and selective tumor cell lysis and induction of apoptosis in melanoma cells by a conditional replication-competent CD95L adenovirusEXPERIMENTAL DERMATOLOGY, Issue 8 2010Lothar F. Fecker Please cite this paper as: Efficient and selective tumor cell lysis and induction of apoptosis in melanoma cells by a conditional replication-competent CD95L adenovirus. Experimental Dermatology 2010; 19: e56,e66. Abstract:, The high mortality of melanoma demands the development of new strategies, and gene therapy may be considered provided improvements in efficacy and selectivity. Overexpression of the death ligand CD95L/FasL has been shown in previous studies as highly effective for apoptosis induction in melanoma cells. For efficient and selective targeting of melanoma, a conditional replication-competent adenoviral vector was constructed (Ad5-FFE-02), which drives CD95L expression by a tetracycline-inducible promoter. For restricting its replication to melanoma cells, the adenoviral E1A gene is controlled by a tyrosinase-derived promoter. Furthermore, adenoviral E1B was deleted and a mutated E1A was used to preferentially support replication in tumor cells. Proving its high selectivity and efficiency, strong expression of E1A and doxycycline-dependent induction of CD95L were characteristic for tyrosinase-positive melanoma cells after Ad5-FFE-02 transduction, whereas absent in non-melanoma cell lines. Importantly, Ad5-FFE-02-mediated cell lysis was restricted to melanoma cells, and induction of apoptosis was found only in tyrosinase and CD95 expressing cells. Finally, the combination of adenoviral replication and CD95L-mediated apoptosis resulted in an enhanced repression of melanoma cell growth. This new adenoviral vector may provide a basis for an efficient targeting of melanoma. [source] Influence of narrowband UVB phototherapy on vitamin D and folate statusEXPERIMENTAL DERMATOLOGY, Issue 8 2010Emanuela Cicarma Please cite this paper as: Influence of narrowband UVB phototherapy on vitamin D and folate status. Experimental Dermatology 2010; 19: e67,e72. Abstract Background:, A variety of studies have shown beneficial effects of different types of phototherapy in skin disorders. Such therapy leads to enhanced cutaneous vitamin D synthesis, which may be one of the mechanisms of action. Furthermore, another nutrient, folate, can probably also be influenced by UV radiation. Objective:, The aim of our study was to investigate the influence of low-dose narrowband UVB (nUVB) phototherapy of patients with psoriasis, atopic eczema and other skin disorders on serum levels of 25(OH) vitamin D (the serum marker for vitamin D status) and on serum and erythrocyte-folate. Methods:, 25(OH) vitamin D (25(OH)D), serum and erythrocyte-folate levels were measured before and after low-dose nUVB (TL-01 tubes) phototherapy of these patients. The spectrum of the TL-01 tube was compared with the solar spectrum, and the efficiency spectra of vitamin D photosynthesis were calculated. Results:, For patients with a high initial 25(OH)D serum level (> 80 nmol/l), no significant (P = 0.36) increase in 25(OH)D levels was seen, in contrast to patients with a low initial level (< 80 nmol/l) where a significant increase (P < 0.001) was observed. The increase was 30,60%, depending on the UVB dose (2.35,13.4 J/cm2). No significant nUVB-effect was found on the erythrocyte and serum-folate level. Conclusion:, Low-dose nUVB treatment gives a significant increase (P < 0.001) of the vitamin D status in persons with low initial levels of 25(OH)D, but no effect on the folate level. [source] Effects of metals on skin permeability barrier recoveryEXPERIMENTAL DERMATOLOGY, Issue 8 2010Mitsuhiro Denda Please cite this paper as: Effects of metals on skin permeability barrier recovery. Experimental Dermatology 2010; 19: e124,e127. Abstract:, We previously demonstrated that the electrical state of the skin surface influences epidermal permeability barrier homeostasis. At the interface between different materials, electrons are localized heterogeneously and induce electrical potential. In the present study, we evaluated the effects of metals on the barrier recovery. When we put pure gold plate on skin immediately after tape stripping, the barrier recovery rate was faster than the control. The acceleration of barrier recovery was blocked when the plate was earthed (grounded). When a plastic membrane was sandwiched between the plate and the skin, the recovery was delayed in comparison with the control. We then used a germanium diode to regulate the current flow between the plate and the earth. When the current was blocked, the barrier recovery was accelerated, but when the current was not blocked, the recovery was not accelerated. These results suggest that localization of electron might affect for the barrier recovery rate. The level of interfacial electric potential would be different due to the electrochemical property of metal. Thus, we next evaluated the effects of other metals. With samarium, zirconium, iridium and silver, the barrier recovery rate was faster than in the case of gold, while a platinum plate induced slower recovery than in the case of gold. There was a significant correlation between work function of each metal and barrier recovery rate. These results suggest that electron donation from outside accelerated the skin barrier recovery. [source] Functional characterization of T cells differentiated in vitro from bone marrow-derived CD34+ cells of psoriatic patients with family historyEXPERIMENTAL DERMATOLOGY, Issue 8 2010Kaiming Zhang Please cite this paper as: Functional characterization of T cells differentiated in vitro from bone marrow-derived CD34+ cells of psoriatic patients with family history. Experimental Dermatology 2010; 19: e128,e135. Abstract Background:, The strong but complex genetic background suggests that inherent and intrinsic rather than exogenous factors have a key role in immunopathogenesis of psoriasis. It is reasonable to speculate that the dysfunctional activity of psoriatic T cells may partly originate from the abnormal haematopoietic cells. Objectives:, To test if T cells originated from haematopoietic progenitor cells in psoriasis patients display functional alternations similar to previously reported abnormalities of circulating T cells. Methods:, Bone marrow CD34+ haematopoietic cells were isolated from psoriatic patients with family history and healthy subjects, and differentiated into T cells in vitro in the thymic stromal co-culture system. These cells were further subjected to functional comparisons such as in vitro proliferation, secretion of cytokines such as IL-4, IL-8 and IFN,,, and inducing the production of C-myc, Bcl-xL, and Ki67 proteins in human keratinocytes. Results:, While bone marrow-derived CD34+ cells from both patients and healthy volunteers developed into mature T cells within weeks in the thymic environment in vitro, the differentiated T cells from psoriatic patients showed higher proliferation and stronger capacity to secret TH1 cytokines in response to streptococcal superantigen. The differentiated T cells from psoriatic patients, but not from normal controls, induced overexpression of C-myc and Ki67, but not Bcl-XL, in keratinocytes. Conclusions:, T cells differentiated from CD34+ cells of psoriatic patients, but not normal controls, are functionally similar to psoriatic circulating T cells, suggesting that the dysfunctional activity of T cells in psoriatic patients can be traced back to the early development of haematopoietic cells. [source] N -acetylcysteine inhibits chromium hypersensitivity in coadjuvant chromium-sensitized albino guinea pigs by suppressing the effects of reactive oxygen speciesEXPERIMENTAL DERMATOLOGY, Issue 8 2010Bour-Jr Wang Please cite this paper as: N -acetylcysteine inhibits chromium hypersensitivity in coadjuvant chromium-sensitized albino guinea pigs by suppressing the effects of reactive oxygen species. Experimental Dermatology 2010; 19: e191,e200. Abstract Background:, Chromium hypersensitivity is an important issue in occupational skin disease. When hexavalent chromium enters the cell, it can be reduced to trivalent chromium, resulting in the formation of reactive oxygen species (ROS). ROS are considered to play an important role in the progression of allergic contact dermatitis. N -acetylcysteine (NAC) could increase glutathione levels in the skin and act as an antioxidant. Aims:, We attempted to demonstrate that NAC could inhibit chromium hypersensitivity in a coadjuvant chromium-sensitized albino guinea pig model by counteracting the formation of ROS. Methods:, We utilized a coadjuvant chromium-sensitized albino guinea pig model to evaluate both the severity of the skin reaction by intradermal and epicutaneous elicitation tests and the sensitization rate of chromium hypersensitivity in NAC-treated and NAC-untreated albino guinea pigs (GP). Furthermore, three ROS parameters, including H2O2, malondialdehyde (MDA) levels in the skin and the oxygen radical absorbance capacity (ORAC) in plasma, were analyzed in NAC-treated and NAC-untreated coadjuvant chromium-sensitized albino GP. Results:, The severity of the skin reaction in the intradermal and epicutaneous elicitation test significantly diminished when the albino GP were treated with a dose of 1200 mg/kg/day of NAC. This dose also significantly decreased the sensitization rate of chromium hypersensitivity. In addition, treatment with 1200 mg/kg/day of NAC significantly reduced the H2O2 and MDA levels in the skin and significantly increased the ORAC in the plasma of albino GP. Therefore, NAC could be a potential chemopreventative agent to prevent the progression of chromium hypersensitivity. [source] Reproducible pattern of microRNA in normal human skinEXPERIMENTAL DERMATOLOGY, Issue 8 2010Line Marie Holst Please cite this paper as: Reproducible pattern of microRNA in normal human skin. Experimental Dermatology 2010; 19: e201,e205. Abstract:, MicroRNAs (miRNAs) regulate cell growth, differentiation and apoptosis via specific targeting of messenger RNA (mRNA). Aberrant mRNA expression contributes to pathological processes such as carcinogenesis. To take advantage of miRNA profiling in skin disease it is essential to investigate miRNA expression pattern in normal human skin. Here we investigated miRNA expression profiles from skin biopsies of 8 healthy volunteers taken from sun protected and mildly photo damaged skin using the modified protocol for miRNA extraction. We were able to show a constant pattern of miRNA expression between different individuals. We did not find any significant differences in miRNA expression between sun protected and mildly photodamaged skin. These results may be valuable for future design of studies on miRNA expression in skin disease. [source] Vitamin C attenuates ERK signalling to inhibit the regulation of collagen production by LL-37 in human dermal fibroblastsEXPERIMENTAL DERMATOLOGY, Issue 8 2010Hyun Jeong Park Please cite this paper as: Vitamin C attenuates ERK signalling to inhibit the regulation of collagen production by LL-37 in human dermal fibroblasts. Experimental Dermatology 2010; 19: e258,e264. Abstract:, Vitamin C is used as an anti-ageing agent because of its collagen enhancing effects. The precise cellular signalling mechanism of vitamin C is not well known. Here, we investigate the profibrotic mechanism of vitamin C against LL-37. Antimicrobial peptide LL-37 decreases collagen expression at mRNA and protein levels in human dermal fibroblasts (HDFs). The ability of LL-37 to inhibit collagen expression is dependent on phosphorylation of extracellular signal-regulated kinase (ERK). HDFs and human keloid fibroblasts were treated with vitamin C followed by 2 h of LL-37 treatment. Collagen mRNA expression and total soluble collagen production inhibited by LL-37 was enhanced by treatment with 0.5 mm vitamin C. Vitamin C also decreased intracellular reactive oxygen intermediates (ROI) levels that were increased by LL-37. Furthermore, the phosphorylation of ERK was analysed by Western blot following treatment with vitamin C and LL-37. Vitamin C turned off phosphorylation of ERK that was induced by LL-37. Ets-1 transcriptional factor, which is involved in the regulation of collagen expression by LL-37, was also inhibited by vitamin C. This study shows that vitamin C enhances collagen production by inhibiting the ERK pathway induced by LL-37. [source] Deposition of chromatin-IgG complexes in skin of nephritic MRL-lpr/lpr mice is associated with increased local matrix metalloprotease activitiesEXPERIMENTAL DERMATOLOGY, Issue 8 2010Annica Hedberg Please cite this paper as: Deposition of chromatin-IgG complexes in skin of nephritic MRL-lpr/lpr mice is associated with increased local matrix metalloprotease activities. Experimental Dermatology 2010; 19: e265,e274. Abstract:, Chromatin-IgG complexes appear as electron dense structures (EDS) in glomerular basement membranes in lupus nephritis. Here, we present results of comparative analyses of the composition of EDS in murine lupus dermatitis and nephritis. One focus was to perform an analytical approach to understand why such complex structures bind skin basement membrane components. Transcription of skin membrane-encoding genes was analysed to see if expression of such genes was increased, eventually indicating that binding capacity of immune complexes increased when dermatitis developed. Variations in matrix metalloprotease 2 (MMP2), MMP9 and Dnase1 mRNA levels and enzymatic activities were correlated with circulatory chromatin-IgG complexes and deposition in skin. We also examined if glomerular deposits of EDS predicted similar deposits in skin of (NZB × NZW)F1 or MRL-lpr/lpr mice, as we observed chromatin-IgG complexes in capillary lumina in skin and glomeruli in both strains. EDS consisting of chromatin fragments and IgG were found sub-epidermally in skin with LE-like lesions of end-stage nephritic MRL-lpr/lpr mice. Dermal MMP-encoding genes were up-regulated during disease progression, and gelatinolytic activity was increased in affected skin. Dnase1 mRNA level and total nuclease activity remained stable in skin during the disease, in contrast to progressive loss of renal Dnase1 mRNA and total renal nuclease activity during development of nephritis. Loss of renal Dnase1 may explain release of chromatin fragments, while increased MMP activity may disrupt membranes making them accessible for chromatin fragment-IgG complexes. Circulatory chromatin-IgG complexes, and up-regulated intradermal MMP activity may be crucial for deposition of immune complexes in skin of lupus-prone mice. [source] About the cutaneous targets of bexarotene in CTCL patientsEXPERIMENTAL DERMATOLOGY, Issue 8 2010Anne Chantal Knol Please cite this paper as: About the cutaneous targets of bexarotene in CTCL patients. Experimental Dermatology 2010; 19: e299,e301. Abstract:, There are several approved therapies for cutaneous T-cell lymphoma (CTCL). The retinoids are one of the major biologic response modifiers used in CTCL, producing good response rates but few complete responses. Bexarotene has been demonstrated to act on malignant T-cells by inducing their apoptosis, but nothing is known about its role on keratinocytes and Langerhans cells. Immunohistochemical analysis using CD1a, HLA-DR, ICAM-1 (activation markers), CD95 and CD40 (apoptosis markers) was conducted on frozen sections of bexarotene-exposed cutaneous explants and skin biopsy specimens from patients treated with bexarotene. None of the studied markers was significantly modulated both on cutaneous explants and on skin biopsy specimens after treatment with bexarotene, compared to controls. Langerhans cells and keratinocytes do not appear to play a central role in the therapeutic control of CTCL by bexarotene therapy. The main bexarotene's target thus remains T-cells by inducing their apoptosis, a mechanism that is different from the other retinoids used in CTCL. [source] Fluorescence induction of protoporphyrin IX by a new 5-aminolevulinic acid nanoemulsion used for photodynamic therapy in a full-thickness ex vivo skin modelEXPERIMENTAL DERMATOLOGY, Issue 8 2010Tim Maisch Please cite this paper as: Fluorescence induction of protoporphyrin IX by a new 5-aminolevulinic acid nanoemulsion used for photodynamic therapy in a full-thickness ex vivo skin model. Experimental Dermatology 2010; 19: e302,e305. Abstract:, An ex vivo porcine skin model was utilized to analyse the penetration of 5-aminolevulinic acid (5-ALA) contained in a nanoemulsion-based formulation BF-200 ALA (10% 5-ALA-hydrochloride) versus 16% aminolevulinate methyl ester-hydrochloride in a commercially cream (MAL cream) by fluorescence microscopy of their common metabolite protoporphyrin IX (PpIX) after 3, 5, 8 and 12 h. Fluorescence signals of PpIX in pig skin treated with BF-200 ALA were stronger than those for MAL cream. At 8 and 12 h, the PpIX fluorescence signals were 4.8- and 5.0-fold higher than those measured after MAL cream application. Fluorescence signals of PpIX after application of BF-200 ALA were detected in deeper tissue layers of the epidermis than after application of MAL cream (97.2 ± 5.7 ,m for BF-200 ALA vs 42.0 ± 4.2 ,m for MAL cream). These data implicate that BF-200 ALA in photodynamic therapy might lead to a superior therapeutically effect of intraepidermal (in situ) squamous cell carcinomas. [source] Gene expression demonstrates increased resilience toward harmful inflammatory stimuli in the proliferating epidermis of human skin woundsEXPERIMENTAL DERMATOLOGY, Issue 8 2010K. Markus Roupé Please cite this paper as: Gene expression demonstrates increased resilience toward harmful inflammatory stimuli in the proliferating epidermis of human skin wounds. Experimental Dermatology 2010; 19: e329,e332. Abstract:, We examined the epidermal gene expression during the proliferative phase of wound healing. Matrix metalloproteases were the group of proteases most prominently up-regulated in skin wounds, whereas serine protease inhibitors were the most strongly up-regulated protease inhibitors. Furthermore, we found down-regulation of genes involved in the extrinsic pathway of apoptosis. This together with the up-regulation of inhibitors of leukocyte serine proteases likely represents a protective step to ensure survival of keratinocytes in the inflammatory wound environment. The down-regulation of proapoptotic genes in the extrinsic pathway of apoptosis was not accompanied by a down-regulation of receptors indicating that the keratinocytes in skin wounds did not become less responsive to external stimuli. Examining the transcription factor binding sites in the promoters of the most differentially expressed genes between normal skin and skin wounds a significant overrepresentation of binding sites were found for STAT-5, SRY and members of the FOXO-family of transcription factors. [source] Differential expression of antimicrobial peptides in margins of chronic woundsEXPERIMENTAL DERMATOLOGY, Issue 7 2010Stefanie Dressel Please cite this paper as: Differential expression of antimicrobial peptides in margins of chronic wounds. Experimental Dermatology 2010; 19: 628,632. Abstract:, Skin wounds usually heal without major infections, although the loss of the mechanical epithelial barrier exposes the tissue to various bacteria. One reason may be the expression of antimicrobial peptides (AMP) of which some [human ,-defensins (hBD) and LL-37] were recently shown to support additionally certain steps of wound healing. There are no studies which have compared expression patterns of different classes of AMP in chronic wounds. The aim of our study was therefore to analyse the expression profile of hBD-2, hBD-3, LL-37, psoriasin and RNase 7 by immunohistochemistry from defined wound margins of chronic venous ulcers. We detected a strong induction of psoriasin and hBD-2 in chronic wounds in comparison with healthy skin. Except for stratum corneum, no expression of RNase 7 and LL-37 was detected in the epidermis while expression of hBD-3 was heterogeneous. Bacterial swabs identified Staphylococcus aureus and additional bacterial populations, but no association between colonization and AMP expression was found. The differential expression of AMP is noteworthy considering the high bacterial load of chronic ulcers. Clinically, supplementation of AMP with the capability to enhance wound healing besides restricting bacterial overgrowth could present a physiological support for treatment of disturbed wound healing. [source] Functional characterization of highly adherent CD34+ keratinocytes isolated from human skinEXPERIMENTAL DERMATOLOGY, Issue 7 2010Araika Gutiérrez-Rivera Please cite this paper as: Functional characterization of highly adherent CD34+ keratinocytes isolated from human skin. Experimental Dermatology 2010; 19: 685,688. Abstract:, Compared to murine models, data on cells responsible for the homeostasis of human epidermis are scarce and often contradictory. Given the conflicting results and the availability of clinical grade protocols to purify CD34 cells from a given tissue, we pursued to phenotypically characterize human epidermal CD34+ population. After magnetic separation of whole skin CD34+ and CD34, cell fractions and selection for cells highly adherent to extracellular matrix, both CD34± fractions retained the ability to form a stratified epidermis in organotypic cultures and presented similar in vitro migratory phenotypes. However CD34, cells showed higher clonogenic potential and in vitro proliferative capacity. These results indicated that CD34, cell fraction contains stem/early progenitor cells, while CD34+ cells might be a transit-amplifying precursor for hair follicle (HF) sheath cells. The ability to isolate living cells using differential cell adhesion and surface markers provides an opportunity to study cells from different morphological regions of the HF. [source] Image-processing chain for a three-dimensional reconstruction of basal cell carcinomas,EXPERIMENTAL DERMATOLOGY, Issue 7 2010Patrick Scheibe Please cite this paper as: Image-processing chain for a three-dimensional reconstruction of basal cell carcinomas. Experimental Dermatology 2010; 19: 689,691. Abstract:, Basal cell carcinoma (BCC) is the most common malignant skin cancer. For a deeper insight into the specific growth patterns of the tumorous tissue in BCC, we have focused on the development of a novel automated image-processing chain for 3D reconstruction of BCC using histopathological serial sections. For fully automatic delineation of the tumor within the tissue, we apply a fuzzy c-means segmentation method. We used a novel multi-grid form of the non-linear registration introduced by Braumann and Kuska in 2005 effectively suppressing registration runs into local minima (possibly caused by diffuse nature of the tumor). Our method was successfully applied in a proof-of-principle study for automated reconstruction. [source] Functional skin adaptation in infancy , almost complete but not fully competentEXPERIMENTAL DERMATOLOGY, Issue 6 2010Joachim W. Fluhr Please cite this paper as: Functional skin adaptation in infancy , almost complete but not fully competent. Experimental Dermatology 2010; 19: 483,492. Abstract:, Early postnatal life is a period of active functional reorganization and cutaneous physiological adaptation to the extrauterine environment. Skin as the outermost organ of mammalians is endowed of multiple functions such as protection, secretion, absorption and thermoregulation. Birth stimulates the epidermal barrier maturation and the skin surface acidification especially in premature infants. In full-term infants the developed stratum corneum accomplishes competent barrier function, in contrast to prematures. Complete barrier maturation in preterm infants is fulfilled by 2,4 weeks of the postnatal life. However, in preterms with 23,25 weeks gestational age this process takes longer. Versatile regulatory mechanisms, namely skin surface acidity, calcium ion gradient and nuclear hormone receptors/ligands are interrelated in the complex postnatal newborn adaptation. The skin of newborns is adjusting quickly to the challenging environmental conditions of the postpartum. However, certain functions, for example, microcirculation, continue to develop even beyond the neonatal period, that is, up to the age of 14,17 weeks. Different environmental factors (for instance, dry and cold climate, diapers and cosmetic care procedures) influence the postnatal development of skin functional parameters such as stratum corneum hydration and the permeability barrier especially in premature infants. The aim of this article is to summarize the current knowledge on skin physiology in newborn and infants with a practical approach and to discuss the possible clinical consequences. This review offers the readership a critical and practical overview of skin physiology in newborns and infants. It emphasizes possible new research fields in neonatal and infantile skin physiology. [source] Prevalence of the MspI and Ile462Val SNPs of Cytochrome P-450 1A1 in Hidradenitis SuppurativaEXPERIMENTAL DERMATOLOGY, Issue 6 2010Ansgar Lukowsky Please cite this paper as: Prevalence of the MspI and Ile462Val SNPs of Cytochrome P-450 1A1 in Hidradenitis Suppurativa. Experimental Dermatology 2010; 19: 541,542. Abstract:, Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease that affects the hair follicles in the axillary, perianal and inguinal area. Its cause and pathogenesis are unknown, but cigarette smoking increases the risk of developing HS conceivably by accumulating toxic metabolites in sweat. The xenobiotic compounds from tobacco are metabolized by the cytochromes P-450. The cytochrome P-450 1A1 (CYP1A1), one of the most active isoenzymes, harbours several polymorphisms. Two of them, MspI and Ile462Val single nucleotide polymorphism (SNP), are associated with enhanced activity and inducibility. Performing direct DNA sequencing, we investigated the frequencies of these SNP in 51 patients with HS, 45 of these were smokers. We found similar overall SNP rates in our patients in comparison with previous data for Caucasian or German controls. Obviously, there is no relation between the occurrence of these SNPs and the risk of developing HS. [source] Human melanocytes can be isolated, propagated and expanded from plucked anagen hair folliclesEXPERIMENTAL DERMATOLOGY, Issue 6 2010Christina Dieckmann Please cite this paper as: Human melanocytes can be isolated, propagated and expanded from plucked anagen hair follicles. Experimental Dermatology 2010; 19: 543,545. Abstract:, Herein, we report a technically simple method for isolation and culture of human follicular melanocytes based on explant cultures of epilated hair follicles. This technique does not require any surgical intervention and allows the isolation and cultivation of follicular melanocytes from a comparatively small amount of raw material. Generally, 30,60 human anagen hair follicles have been plucked from the scalp of healthy donors and cultivated under low oxygen pressure (5%). After a short period of time cells of various types were growing out from the outer root sheath (ORS) of the hair follicles. Under the selected culture conditions, most of the cells other than melanocytes have been eliminated and a nearly 100% pure population of melanocytes has been achieved, as confirmed by immunohistochemical analyses for melanocyte-specific markers, for example, Tyrosinase-1, S-100 and premelanosomal antigens. These melanocytes derived from the ORS were proliferating for up to 2 months. [source] Is there a ,gut,brain,skin axis'?EXPERIMENTAL DERMATOLOGY, Issue 5 2010Petra Arck Please cite this paper as: Is there a ,gut,brain,skin axis'? Experimental Dermatology 2010; 19: 401,405. Abstract:, Emerging evidence arising from interdisciplinary research supports the occurrence of communication axes between organs, such as the brain,gut or brain,skin axis. The latter is employed in response to stress challenge, along which neurogenic skin inflammation and hair growth inhibition is mediated. We now show that ingestion of a Lactobacillus strain in mice dampens stress-induced neurogenic skin inflammation and the hair growth inhibition. In conclusion, we are introducing a hypothesis, encouraged by our pilot observations and resting upon published prior evidence from the literature, which amalgamates previously proposed partial concepts into a new, unifying model, i.e. the gut,brain,skin axis. This concept suggests that modulation of the microbiome by deployment of probiotics can not only greatly reduce stress-induced neurogenic skin inflammation but even affect a very complex cutaneous phenomenon of (mini-) organ transformation, i.e. hair follicle cycling. These observations raise the intriguing prospect that feeding of just the right kind of bacteria can exert profound beneficial effects on skin homoeostasis, skin inflammation, hair growth and peripheral tissue responses to perceived stress. [source] Novel ELISA systems for antibodies to desmoglein 1 and 3: correlation of disease activity with serum autoantibody levels in individual pemphigus patientsEXPERIMENTAL DERMATOLOGY, Issue 5 2010Enno Schmidt Please cite this paper as: Novel ELISA systems for antibodies to desmoglein 1 and 3: correlation of disease activity with serum autoantibody levels in individual pemphigus patients. Experimental Dermatology 2010; 19: 458,463. Abstract:, Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are intraepidermal blistering skin diseases. PV is characterised by autoantibodies directed against desmoglein (Dsg) 3 and in patients with the mucocutaneous variant also against Dsg 1, whereas in PF, only Dsg 1 is targeted. Here, ectodomains of Dsg 3 and Dsg 1 were recombinantly expressed in a human cell line (HEK293) and applied as authentic solid phases in ELISA test systems. Autoantibodies against Dsg 3 and/or Dsg 1 could be detected in 71 (100%) of 71 PV sera and against Dsg 1 in 48 (96%) of 50 PF sera. Control sera showed reactivity with Dsg 3 and Dsg 1 in 0.2% and 0.7%, respectively, of 401 healthy blood donors and in 2.1% of 48 randomly selected patients with bullous pemphigoid. No reactivity with Dsg 1 and 3 was detected in 21 patients with linear IgA disease. For both pemphigus variants, a statistically significant correlation between clinical severity and autoantibody levels was observed as demonstrated for 10 PV and 5 PF patients. In conclusion, the use of the ectodomains of Dsg 3 and 1 as target antigens expressed in a human cell line resulted in sensitive and specific ELISA systems for both diagnosis and monitoring of PV and PF. [source] Increased levels of serum IL-31 in chronic spontaneous urticaria,EXPERIMENTAL DERMATOLOGY, Issue 5 2010Ulrike Raap Please cite this paper as: Increased levels of serum IL-31 in chronic spontaneous urticaria. Experimental Dermatology 2010; 19: 464,466. Abstract:, IL-31 represents a novel cytokine involved in pruritic skin diseases including atopic dermatitis (AD). We, therefore, aimed at investigating IL-31 levels in chronic spontaneous urticaria (CU). We included 46 patients with CU, 26 non-atopic skin healthy subjects as negative and 28 patients with AD as positive controls. IL-31 serum levels were analysed using commercial ELISA kit. IL-31 serum levels were higher in patients with CU compared to healthy controls (P < 0.001), but lower compared to patients with AD (P < 0.001). There was no difference in IL-31 serum levels in autologous serum skin test positive or negative CU patients and patients with infectious trigger factors including helicobacter pylori infection. IL-31 serum levels may play a role in the pathophysiology of CU. This is supported by the finding that not all patients with CU respond to antihistamine treatment but to the treatment with immunosuppressive drugs. [source] Atopic eczema or atopiform dermatitisEXPERIMENTAL DERMATOLOGY, Issue 4 2010Jan D. Bos Please cite this paper as: Atopic eczema or atopiform dermatitis. Experimental Dermatology 2010. Abstract:, Age period prevalence of atopic eczema (AE), a very common skin disease, has increased during the past decennia. This expansion seems to be ending in wealthy countries, while an increase is observed in developing nations, for which there is no firm explanation. Recent steps in understanding AE are the detection of skin barrier related filaggrin null mutations in approximately 25% of patients and the recognition of IL-31 as a molecule possibly involved in the itch (pruritus). Also interesting are the recognition of thymus and activation-regulated chemokine (TARC) and proliferating-inducing ligand (APRIL), as being associated with AE severity and activity. Immunocentric and corneocentric views on pathogenesis (the inside-outside paradigm) and the diagnostic entity atopiform dermatitis (AFD) are discussed here. We emphasize that diagnosing AE is not simple but challenging. We accentuate that a diagnosis of AE is only possible when there is allergen-specific IgE. Advice as to the need for elimination of allergens and adjustment of lifestyle are only proficient in patients having atopy and true AE, not in those having AFD. [source] Exploration of the functional hierarchy of the basal layer of human epidermis at the single-cell level using parallel clonal microcultures of keratinocytesEXPERIMENTAL DERMATOLOGY, Issue 4 2010Nicolas O. Fortunel Please cite this paper as: Exploration of the functional hierarchy of the basal layer of human epidermis at the single-cell level using parallel clonal microcultures of keratinocytes. Experimental Dermatology 2010. Abstract:, The basal layer of human epidermis contains both stem cells and keratinocyte progenitors. Because of this cellular heterogeneity, the development of methods suitable for investigations at a clonal level is dramatically needed. Here, we describe a new method that allows multi-parallel clonal cultures of basal keratinocytes. Immediately after extraction from tissue samples, cells are sorted by flow cytometry based on their high integrin-,6 expression and plated individually in microculture wells. This automated cell deposition process enables large-scale characterization of primary clonogenic capacities. The resulting clonal growth profile provided a precise assessment of basal keratinocyte hierarchy, as the size distribution of 14-day-old clones ranged from abortive to highly proliferative clones containing 1.7 × 105 keratinocytes (17.4 cell doublings). Importantly, these 14-day-old primary clones could be used to generate three-dimensional reconstructed epidermis with the progeny of a single cell. In long-term cultures, a fraction of highly proliferative clones could sustain extensive expansion of >100 population doublings over 14 weeks and exhibited long-term epidermis reconstruction potency, thus fulfilling candidate stem cell functional criteria. In summary, parallel clonal microcultures provide a relevant model for single-cell studies on interfollicular keratinocytes, which could be also used in other epithelial models, including hair follicle and cornea. The data obtained using this system support the hierarchical model of basal keratinocyte organization in human interfollicular epidermis. [source] Patterns in naevoid skin disease: development, disease and modellingEXPERIMENTAL DERMATOLOGY, Issue 3 2010Stephen J. Gilmore Please cite this paper as: Patterns in naevoid skin disease: development, disease and modelling. Experimental Dermatology 2010; 19: 240,245. Abstract:, The aetiology of pattern-formation in human naevoid skin disease remains unknown. However, it is likely that the majority of previously proposed mechanisms , those that simply rely on passive clonal trafficking in embryogenesis , are incomplete. A more comprehensive explanation for pattern-formation in naevi invokes the principle of self-organization. We define two types of patterning: anatomical and functional. Anatomical patterning is where the abnormal clone is limited to regions of pathologic skin, while functional patterning is where the abnormal clone and pathologic skin are spatially uncorrelated. From a theoretical perspective self-organized naevoid patterns may be either secondary to local interactions between normal and aberrant genotypes or due to the interaction between aberrant genotypes and the presence of normal embryonic patterning cues. The latter possibility suggests the critical observation and analysis of patterns in naevoid skin disease may lead to unique insights into key aspects of early human embryogenesis. [source] | ||||||||||