MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Experimental Dermatology' source. Wed, 08 Feb 2012 13:12:30 +0100 http://www.medworm.com/index.php?rid=5659830&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01466.x (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5659830 Fri, 03 Feb 2012 05:00:00 +0100 5659830 http://www.medworm.com/index.php?rid=5659829&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01467.x AbstractPeroxisome Proliferator‐activated receptors‐α (PPARs‐α) are nuclear receptors with anti‐inflammatory properties. Zinc gluconate is efficient in the treatment of several inflammatory dermatoses. The aim of our work was to determine whether the modulation of PPAR‐α expression and activity could be one of the mechanisms of action of zinc gluconate anti‐inflammatory activity in inflammatory dermatoses. Thus, we used ex vivo skin explants incubated with Lipopolysaccharide (LPS), a pro‐inflammatory molecule, with or without zinc gluconate. We evaluated PPAR‐α protein expression using immunohistochemistry, PPAR‐α DNA binding activity using an ELISA‐like technique, and PPAR‐α mRNA levels using quantitative PCR. On the one hand, we found that PPAR‐α epidermal ... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5659829 Wed, 01 Feb 2012 05:00:00 +0100 5659829 http://www.medworm.com/index.php?rid=5647928&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01465.x AbstractThe aim of this study was to assess the effects of ultraviolet B (UVB) irradiation on microRNA (miRNA) expression in normal human keratinocytes. Global miRNA expression profiles of primary cultures of normal human keratinocytes 4 and 24 hours post‐irradiation were studied using miRNA microarray with further confirmation by real‐time PCR. We found that upon 30 or 60 mJ/cm2 of UVB radiation, the expression of 44 miRNAs were up‐ or downregulated more than 2‐fold compared to non‐irradiated keratinocytes. MiRNAs were either up‐ or downregulated after 4 hours, and then either returned to normal levels or remained affected after 24 hours, resulting in 4 distinct patterns of miRNA expression change. It appears that acute exposure of keratinocytes to UVB radiation results in sev... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5647928 Wed, 01 Feb 2012 05:00:00 +0100 5647928 http://www.medworm.com/index.php?rid=5638553&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01463.x AbstractSebocytes originate from the same lineage as keratinocytes and both cell types may have similarities in terms of growth and differentiation. We were interested in studying the behaviour of human sebocytes when cultured in conditions validated for epidermal reconstruction. For this purpose, we established a HPV16‐E6/7‐immortalized human sebocyte cell line (SEBO662) growing in keratinocyte defined media.Post‐confluent SEBO662 cells in monolayers express the early sebocyte marker, cytokeratin 7 (K7), do not express Epithelia Membrane Antigen (EMA) and do not exhibit strong lipogenic activity. However, when placed at the air‐liquid interface, SEBO662 multilayers spontaneously differentiate into a sebaceous‐like structure as shown by the strong polarized expression of the late... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5638553 Sun, 29 Jan 2012 17:36:02 +0100 5638553 http://www.medworm.com/index.php?rid=5638558&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01462.x AbstractMicroRNAs are short non‐coding RNAs that regulate gene expression. Previously, in a genome‐wide screen we found deregulation of microRNA expression in psoriasis skin. MicroRNA‐21 (miR‐21) is one of the microRNAs significantly up‐regulated in psoriasis skin lesions. In order to identify the cell type responsible for the increased miR‐21 level, we compared expression of miR‐21 in epidermal cells and dermal T cells between psoriasis and healthy skin and found elevated levels of miR‐21 in psoriasis in both cell types. In cultured T cells, expression of miR‐21 increased markedly upon activation. In order to explore the function of miR‐21 in primary human T helper cells, we inhibited miR‐21 using a tiny seed‐targeting LNA‐antimiR. Specific inhibition of miR‐21... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5638558 Fri, 27 Jan 2012 05:00:00 +0100 5638558 http://www.medworm.com/index.php?rid=5638557&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01458.x This study may provide valuable information to establish a culture method of human DPCs for cell‐based therapy. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5638557 Fri, 27 Jan 2012 05:00:00 +0100 5638557 http://www.medworm.com/index.php?rid=5638556&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01459.x AbstractEpidermal keratinocytes produce and secrete antimicrobial peptides which subsequently form a chemical shield on the skin surface. Cathelicidins are one family of antimicrobial peptides in skin with various further immune functions. Consequently, dysfunction of these peptides has been implicated in the pathogenesis of inflammatory skin disease. In particular, the cathelicidin LL‐37 is overexpressed in inflamed skin in psoriasis, binds to extracellular self‐DNA released from dying cells and converts self‐DNA in a potent stimulus for plasmacytoid dendritic cells (pDCs). Subsequently, pDCs secrete type‐I interferons and trigger an auto‐inflammatory cascade. Paradoxically, therapies targeting the vitamin D pathway such as vitamin D analogues or UVB phototherapy ameliorate cuta... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5638556 Fri, 27 Jan 2012 05:00:00 +0100 5638556 http://www.medworm.com/index.php?rid=5638555&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01460.x AbstractPsoriasis is an inflammatory skin disease often associated with obesity. The anti‐inflammatory adipokine vaspin, a suggested serine proteinase inhibitor of the serpin family, is discussed as a new link between inflammation and obesity. Here we demonstrate that ‐ different from healthy controls ‐ vaspin serum levels in psoriatic patients were BMI‐independent. Moreover, we could identify keratinocytes as the major source of vaspin in skin. Vaspin expression in lesional psoriatic skin was reduced compared to uninvolved skin as shown by immunohistochemistry and RT‐PCR. In aggregate we report on the cellular source of vaspin in skin and its expression in psoriasis. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5638555 Fri, 27 Jan 2012 05:00:00 +0100 5638555 http://www.medworm.com/index.php?rid=5638554&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01461.x AbstractMalignant melanoma is a tumour characterized by the uncontrolled proliferation of melanocytes, mainly in skin, but also in eyes. Its incidence is rising each year. To improve the diagnosis and treatment of the tumour, it is essential to develop new effective methods to early detect and characterize melanoma. Previously, we demonstrated in a single‐shot study that it was possible to map free radicals of melanin pigments using an electron paramagnetic resonance (EPR)‐based method. Furthermore, we demonstrated that X‐Band (9 GHz) EPR spectrometry was an accurate tool to assess the growth stage of a pigmented tumour. The aim of the present study was to investigate the ability of EPR imaging to detect and localize melanin pigments inside melanin phantoms, B16 melanoma tumor models... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5638554 Fri, 27 Jan 2012 05:00:00 +0100 5638554 http://www.medworm.com/index.php?rid=5628749&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01457.x AbstractThe hair cycle and its control remain today an object of debate. A number of factors have been identified which can modulate this process, but its choreography remains elusive. For years, the hunt for the conductor has been on, but nobody ever caught him. Intuitively, the process being considered as cyclic, an automaton controlling this cycle should be looked for, by analogy with a clock. However, the putative hair follicle oscillator that would control hair cycle failed to be identified and characterized. In fact, we have revealed that human hair follicle has an autonomous behavior and that the transitions from one phase to the next occur independently for each follicle, after time intervals given stochastically by a lognormal distribution characterized by a mean and a variance. F... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5628749 Thu, 26 Jan 2012 17:56:57 +0100 5628749 http://www.medworm.com/index.php?rid=5620181&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01455.x AbstractOrange peel extract appears to exhibit beneficial effects on skin whitening, inflammation, UVB protection, as well as keratinocyte proliferation. In the present study, we determine whether topical hesperidin influences epidermal permeability barrier function and its underlying mechanisms. Hairless mice were treated topically with 2% hesperidin or 70% ethanol alone twice daily for 6 days. At the end of treatment, basal barrier function as well as transepidermal water loss (TEWL) was measured 2 and 4 hours post barrier disruption. Epidermal proliferation and differentiation were evaluated by immunohistochemical staining and Western blot analysis. Additionally, lamellar body density and secretion were assessed by electron microscopy. Although there were no significant differences in b... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5620181 Mon, 23 Jan 2012 17:36:08 +0100 5620181 http://www.medworm.com/index.php?rid=5620183&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01453.x AbstractA calcium gradient in skin epidermis is known to regulate epidermal differentiation. In cultures of human epidermal keratinocytes (NHEK), induction of calcium‐dependent differentiation is associated with phosphorylation of ErbB receptors, including the epidermal growth factor receptor (EGFR). The activation of EGFR triggers the induction of activator protein 1 (AP‐1) proteins necessary for keratinocyte terminal differentiation. Interestingly, an in vitro long‐term calcium treatment revealed the activation of different ErbB receptors with different timings, which is consistent with the differential localization of each receptor in the skin layers in vivo. In the current study, the regulatory relationship between ErbB receptor activation and induction of AP‐1 proteins in calc... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5620183 Mon, 23 Jan 2012 05:00:00 +0100 5620183 http://www.medworm.com/index.php?rid=5620182&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01454.x In this study, we examined the role of periostin in the process of cutaneous wound repair using periostin‐deficient mice and by analyzing the effects of periostin on dermal fibroblasts. We first determined the expression profile and localization of periostin in a well characterized wound repair model mice. Periostin was robustly deposited in the granulation tissues beneath the extended epidermal wound edges and at the dermal‐epidermal junctions in wounded mice. Moreover, periostin‐deficient mice exhibited delayed in vivo wound repair, which could be improved by direct administration of exogenous periostin. In vitro analyses revealed that loss of periostin impaired proliferation and migration of dermal fibroblasts, but exogenous supplementation or enforced periostin expression enhance... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5620182 Mon, 23 Jan 2012 05:00:00 +0100 5620182 http://www.medworm.com/index.php?rid=5608938&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01452.x AbstractFailure to execute an apoptotic program is one of the critical steps and a common mechanism promoting tumorogenesis. Immediate early responsive gene 3 (IER3) has been shown to be upregulated in several cancers. IER3 is a stress induced gene, which upregulation leads to reduction in production of reactive oxygen species (ROS) protecting malignant cells from apoptosis. We observed that malignant lymphocytes from patients with Sézary syndrome (SzS) were resistant to pro‐apoptotic dose of tumor necrosis factor‐α (TNF‐α). The aim of this study was to investigate the role of IER3 in the mechanism of such resistance. CD4+ CD26‐ lymphocytes from the peripheral blood of patients with SzS and healthy controls were negatively selected using CD4 and CD26 magnetic beads and analyzed ... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5608938 Fri, 20 Jan 2012 17:32:21 +0100 5608938 http://www.medworm.com/index.php?rid=5597806&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01447.x AbstractIn the 1970s studies of tissue architecture and cell proliferation were used to formulate a new model of epidermal homeostasis. This asserted that the tissue was maintained by long lived, slow cycling, self‐renewing stem cells that generate a short lived population of transit amplifying (TA) cells which undergo terminal differentiation after a set number of cell divisions. In the epidermis, it was further hypothesized that the tissue was organized into clonal epidermal proliferative units (EPU) comprising a central stem cell with surrounding transit amplifying cells, which maintain the overlying differentiated cell layers. The stem/TA and EPU hypotheses have been widely influential. Here we first revaluate older literature, finding numerous studies which conflict with the EPU mod... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5597806 Tue, 17 Jan 2012 18:00:14 +0100 5597806 http://www.medworm.com/index.php?rid=5608942&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01449.x AbstractThe S100 fused‐type proteins are thought to be involved in the barrier formation and function of the skin. Mutations in the profilaggrin gene, one of the best investigated members of this family, are known to be major risk factors for ichthyosis vulgaris and atopic dermatitis. Recently, we identified human filaggrin‐2 as a new member of the S100 fused‐type protein family. To get further insight into its function here the murine filaggrin‐2 was analyzed as a possible orthologue. The 5’ and 3’ ends of the mouse filaggrin‐2 cDNA of the BALB/c strain were sequenced and confirmed an organization typical for S100 fused‐type proteins. Murine filaggrin‐2 showed an expression pattern mainly in keratinizing epithelia in the upper cell layers both on mRNA and protein level. ... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5608942 Tue, 17 Jan 2012 05:00:00 +0100 5608942 http://www.medworm.com/index.php?rid=5608941&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01448.x In this study we show that activation of YB‐1 by S102‐phosphorylation and nuclear translocation is increased during melanoma progression using a human tissue microarray with 100 melanocytic lesions. Furthermore, we analyzed the mechanisms governing the expression and activity of YB‐1 in melanoma cells. We show that the PI3K/AKT and p53 signaling, growth factors and chemotherapeutic agents increase YB‐1 promoter activity. This, however, resulted in no or only modest increase in YB‐1 protein expression. We show that the MAPK and PI3K/AKT signaling pathways, both activated in melanoma cells, as well as p53 overexpression increase YB‐1 S102‐phosphorylation, whereas NFκB signaling inhibits phosphorylation. Overexpression of YB‐1 in melanoma cells inhibits translation efficiency... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5608941 Tue, 17 Jan 2012 05:00:00 +0100 5608941 http://www.medworm.com/index.php?rid=5608940&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01450.x AbstractKeloids are characterized by extreme fibroblastic overgrowth of unknown pathogenesis after skin injury. Previous studies, mostly in non‐Caucasian populations, suggest that p53 mutations may be involved. To substantiate this, we performed DNA sequence analysis of exons 4‐8 of the p53 gene and immunohistochemical staining of p53 protein in archived keloidal tissue samples from 23 Caucasian patients. In contrast to previous reports, we found mutated p53 in keloidal tissue in a minority of cases (2/23; 12%). The G allele frequency and C allele frequency at the p53 polymorphic codon 72 was 0.72 (33/46) and 0.28 (13/46), respectively, in our study, a finding that was similar to the 0.77 (184/240) vs. 0.23 (56/240) (P=0.4580; χ2 test) observed in the Hap Map data of a European popula... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5608940 Tue, 17 Jan 2012 05:00:00 +0100 5608940 http://www.medworm.com/index.php?rid=5608939&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01451.x The objective of our work was to identify RCM parameters able to quantify in vivo dermis papilla density and epidermis pigmentation potentially applicable in clinical studies. The study included 111 healthy female volunteers with phototype I to VI. Photo‐exposed and photo‐protected anatomical sites were imaged. The effect of age was also assessed. Four epidermis components were specifically investigated: stratum corneum, stratum spinosum, basal epidermal layer, and dermo‐epidermal junction. Laser power, diameter of corneocytes and upper spinous keratinocytes, brightness of upper spinous and interpapillary spinous keratinocytes, number of dermal papillae and papillary contrast were systematically assessed. Papillary contrast measured at the dermo‐epidermal junction appeared to be a ... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5608939 Tue, 17 Jan 2012 05:00:00 +0100 5608939 http://www.medworm.com/index.php?rid=5597808&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01445.x AbstractMicroRNAs are non‐coding RNA molecules modulating gene expression post‐transcriptionally. FFPE is a standard preservation method often used in clinical practices, but induces RNA degradation. Extracting high quality RNA from human skin can be challenging as skin contains high levels of RNases. As microRNAs are 19‐23 nucleotides long and lack a poly‐A tail, they may be less prone to RNA degradation than mRNAs. We investigated whether microRNAs in psoriatic FFPE samples reliably reflect microRNA expression in samples less prone to RNA degradation such as fresh‐frozen (FS) and Tissue‐Tek‐embedding (OCT). We found a strong correlation of the microRNA expression‐levels between all preservation methods of matched psoriatic skin samples (rs ranging from 0.91–0.95 (P<0... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5597808 Mon, 16 Jan 2012 05:00:00 +0100 5597808 http://www.medworm.com/index.php?rid=5597807&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01446.x We describe an unusual xeroderma pigmentosum (XP) patient with a mutation in XP complementation group G, representing only the third reported Japanese XP‐G patient. A 40‐year‐old male (XP3HM), born from consanguineous parents experienced sun sensitivity and pigmentary changes of sun‐exposed skin since childhood. He developed a squamous cell carcinoma on his lower lip at the age of 40. He has neither neurological abnormalities nor Cockayne syndrome. The primary fibroblasts of the patient were hypersensitive to killing by UV (D0=0.6 J/m2) and the post‐UV unscheduled DNA synthesis was 8% of normal. Host cell reactivation complementation analysis implicated XP complementation group G. We identified a novel homozygous mutation (c.194T>C) in a conserved portion of the XPG(ERCC5) gen... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5597807 Mon, 16 Jan 2012 05:00:00 +0100 5597807 http://www.medworm.com/index.php?rid=5581934&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01412.x Abstract:  Atopic eczema and psoriasis are common skin diseases. While it is well established that the pathogenesis of these diseases varies, both are characterized by impairment in epidermal barrier function and abnormal IL‐17 expression in the skin and peripheral blood. Recent findings indicated that filaggrin is essential during barrier formation and its insufficiency underlies the pathogenesis of atopic eczema. Filaggrin downregulation has also been reported in psoriasis. It is clear that Th1/Th2 bias influences expression of the protein, but an analysis of the effects of interleukin‐17 (IL‐17) on the expression of the protein and profilaggrin‐processing enzymes has not yet been reported. In addition, the effect of the cytokine on components of functional epidermal barrier, t... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5581934 Fri, 13 Jan 2012 22:25:00 +0100 5581934 http://www.medworm.com/index.php?rid=5581931&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01443.x We describe the case of a man with a lower leg amputation who presented HS‐like lesions on his leg stump after wearing a leg prosthesis. Although pilonidal sinus‐like disease could not be excluded we diagnosed him with HS‐like lesions, induced by prosthesis‐related friction. We argue that this case supports the concept that mechanical friction and a warm humid microclimate by occlusion contribute to HS development. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5581931 Fri, 13 Jan 2012 22:24:17 +0100 5581931 http://www.medworm.com/index.php?rid=5581933&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01441.x In conclusion, our data reveal a novel role for phosphorylated FAK (Y397/925) in PV development involving HER isoforms, Src and mTOR kinases. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5581933 Wed, 11 Jan 2012 05:00:00 +0100 5581933 http://www.medworm.com/index.php?rid=5581932&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01442.x In conclusion, HAL express high affinity for epidermis and sebaceous gland epithelium, and MAL for actinically damaged skin, which raises future perspectives for improved selectivity in PDT. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5581932 Wed, 11 Jan 2012 05:00:00 +0100 5581932 http://www.medworm.com/index.php?rid=5560239&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01438.x AbstractUltraviolet (UV) radiation contained in sunlight is considered a major risk in the induction of skin cancer. While mast cells are best known for their role in allergic responses they have also been shown to play a crucial role in suppressing the anti‐tumour immune response following UV exposure. Evidence is now emerging that UV may also trigger mast cell release of cutaneous tissue remodelling and pro‐angiogenic factors. In this review, we will focus on the cellular and molecular mechanisms by which UV recruits and then activates mast cells to initiate and promote skin cancer development. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5560239 Wed, 04 Jan 2012 05:00:00 +0100 5560239 http://www.medworm.com/index.php?rid=5572238&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01440.x AbstractDrug resistance is arguably the most important challenge in cancer therapy. Here, doxorubicin induced profound of NF‐κB activation in melanoma cells with a maximum (3.5‐fold) at concentrations relevant in vivo. This was followed by transcriptional induction of several gene products involved in tumor progression. A novel IKKα inhibitor (BAY32‐5915) was identified and characterized, and doxorubicin‐induced NF‐κB activation was assessed following inhibition of IKKα or IKKβ by small‐molecular compounds. While the IKKα inhibitor did not affect doxorubicin‐induced NF‐κB activation, this process was completely abrogated when the IKKβ inhibitor, KINK‐1, was used. Moreover, inhibition of IKKβ, but not IKKα, led to significantly increased apoptosis in response to ... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5572238 Sun, 01 Jan 2012 05:00:00 +0100 5572238 http://www.medworm.com/index.php?rid=5560238&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2012.01439.x AbstractSirtuins (SIRT) are NAD+‐dependent deacetylases and ADP‐ribosyltransferases that play a critical role in metabolism and epigenetics. SIRT3 and SIRT4 are of particular interest because they are localized in the mitochondria where energy is generated and their expression is inversely proportional to each other. Here, we report data, for the first time, demonstrating the presence of SIRT4 in normal human epidermal keratinocytes (NHEK) and confirm that its expression is inversely related to SIRT3 in these cells and that they follow a temporal cycle. Further, UVB radiation modified their expression, as well as ATP and H2O2 levels. These deviations from the normal sirtuin cycles after UVB exposure can be an epigenetic indicator of lower metabolism levels. (Source: Experimental Dermat... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5560238 Sun, 01 Jan 2012 05:00:00 +0100 5560238 http://www.medworm.com/index.php?rid=5524860&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01437.x Abstract8‐methoxypsoralen plus UVA (PUVA) photochemotherapy is an effective treatment for many skin diseases including psoriasis. However, its exact mechanism of therapeutic action is incompletely understood. Previously, in K5.hTGFβ1 transgenic psoriatic mice, we found that PUVA induces Foxp3+CD25+CD4+ regulatory T cells in both lymph node and spleen. Now, in the same model, we investigated whether cutaneous lymphocyte‐associated antigen (CLA) mediates PUVA’s effect on homing of CD25+CD4+ T cells to the lymph nodes of K5.hTGFβ1 transgenic mice. We found that a low dose of topical PUVA maximally increased the proportion of CLA+CD25+CD4+ T cells in the lymph nodes by up to 8‐fold. We also observed an increased number of Foxp3+CD25+ T cells in the skin of the mice after PUVA treatme... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5524860 Thu, 22 Dec 2011 06:00:18 +0100 5524860 http://www.medworm.com/index.php?rid=5524864&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01433.x AbstractItch accompanies various skin diseases. As a number of mediators other than histamine can be involved in the itch sensation, H1 receptor antagonists are not necessarily effective in treating itch. External application of anti‐pruritic drugs is occasionally used as an alternative therapy for pruritic skin conditions, such as pruritus on primary non‐diseased, non‐inflamed skin. Even so, the actual effects of these drugs on the itch sensation have yet to be studied in detail. To verify the anti‐pruritic effects of crotamiton, capsaicin, and a corticosteroid on the itch sensation, we examined the inhibitory effects of these drugs on various pruritogen‐induced scratching behaviors in mice. Topical application of 10% crotamiton moderately inhibited histamine‐, serotonin‐, a... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5524864 Tue, 20 Dec 2011 05:00:00 +0100 5524864 http://www.medworm.com/index.php?rid=5524863&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01434.x AbstractA proteomic analysis of Stratum Corneum (SC) samples of normal healthy skin revealed the presence of more than 70 proteins by 2D‐electrophoresis. The majority of these proteins to our knowledge have not yet been described in normal SC. We analyzed by Western Blot the levels of twenty five proteins in the SC taken from postmenopausal and dry skin compared to young and normal skin respectively. In postmenopausal skin, there was a significantly increased amount of Heat Shock Protein 27 (HSP27), Plakoglobin (PKG) and Desmoglein1 (DSG1) whereas Transglutaminase 3 (TGM3), ApolipoproteinD (APOD) and Acid Ceramidase (ASAH1) levels were significantly reduced compared to the SC of young skin. We confirmed Corneodesmosin (CDSN) as a marker of dry skin. In addition, we showed for the first t... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5524863 Tue, 20 Dec 2011 05:00:00 +0100 5524863 http://www.medworm.com/index.php?rid=5524862&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01435.x AbstractPeroxisome proliferator‐activated receptors (PPARs), which are members of the nuclear hormone receptor superfamily, are a family of ligand‐activated transcription factors that consists of three isotypes (PPAR α, δ, and γ). PPAR activity was previously thought to be limited to lipid metabolism and glucose homeostasis; however, intensive studies of PPARα/γ in recent years have revealed their importance in age‐related inflammation and photoaging as regulators of cytokines, matrix metalloproteinases (MMPs), and nuclear factor‐kappa B (NF‐κB). We evaluated the ability of the PPARα/γ activator 5,7‐dimethoxyflavone (5,7‐DMF) to inhibit ultraviolet B (UVB)‐induced MMP expression in Hs68 human skin fibroblasts.Hs68 cells were treated with 5,7‐DMF and then exposed t... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5524862 Tue, 20 Dec 2011 05:00:00 +0100 5524862 http://www.medworm.com/index.php?rid=5524861&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01436.x AbstractPosttranscriptional managing of RNA plays a key role in the intricate network of cellular pathways that regulate our genes. Numerous small RNA species have emerged as crucial regulators of RNA processing and translation. Among these, microRNAs (miRNAs) regulate protein synthesis through specific interactions with target RNAs, and are believed to play a role in almost any cellular process and tissue. Skin is no exception, and miRNAs are intensively studied for their role in skin homeostasis and as potential triggers of disease. For use in skin and many other tissues, therapeutic RNA managing by small RNA technologies is now widely explored. Despite the easy accessibility of skin, the natural barrier properties of skin have challenged genetic intervention studies, and unique tools fo... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5524861 Tue, 20 Dec 2011 05:00:00 +0100 5524861 http://www.medworm.com/index.php?rid=5504969&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01432.x AbstractInterferon‐γ (IFNγ)‐induced collapse of hair follicle (HF) immune privilege (IP) is a key element in the pathogenesis of alopecia areata. In this pilot study, we investigated whether the immunosuppressive neuropeptide, calcitonin gene‐related peptide (CGRP), can protect from and/or restore IFNγ‐induced HF IP‐collapse. After showing that human scalp HFs express CGRP receptor‐like (CRLR) immunoreactivity, anagen HFs were cultured in the presence of IFNγ, with CGRP added before or after. Adding CGRP after IFNγ administration (“restoration assay”) failed to downregulate IFNγ‐induced ectopic MHC class I expression, while MHC class II expression was reduced. However, administering CGRP before IFNγ application (“protection assay”) significantly reduced the IFN... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5504969 Fri, 16 Dec 2011 05:59:37 +0100 5504969 http://www.medworm.com/index.php?rid=5504970&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01431.x AbstractSkin barrier function is indispensable to prevent the uncontrolled loss of water and solutes and to protect the body from external assaults. To fulfill this function keratinocytes undergo a complex pathway of differentiation which terminates in the formation of the stratum corneum. Additionally, tight junctions (TJs), which are cell‐cell junctions localized in the stratum granulosum, are involved in the barrier function of the skin. Important biological and clinical roles of TJs are strongly suggested by altered TJ protein levels and distribution in skin diseases like psoriasis, ichthyosis, and atopic dermatitis. Because these skin diseases show alterations of differentiation and TJs, it was suggested that changes in TJs might simply be a consequence of altered differentiation. H... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5504970 Thu, 15 Dec 2011 05:00:00 +0100 5504970 http://www.medworm.com/index.php?rid=5494972&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01406.x Abstract:  Lipo‐PGE1 [EGLANDIN®; a lipid microsphere‐incorporated prostaglandin E1 (PGE1)] stimulates angiogenesis and promotes the healing of skin ulcers. Because the effects of Lipo‐PGE1 on cutaneous wound healing are not completely understood, we investigated the ability of Lipo‐PGE1 to affect in vivo wound healing and regulate the migration of human dermal fibroblasts (HDFs). In a murine wound model, Lipo‐PGE1 reduced the wound size compared with control mice. Lipo‐PGE1 significantly increased HDF migration in a dose‐ and time‐dependent manner. Lipo‐PGE1 markedly increased the expression of CXC chemokine receptor 4 (CXCR4), which controls the migration of HDFs, at the mRNA and protein levels. Small interfering RNA (siRNA)‐mediated knockdown of CXCR4 inhibited Lip... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5494972 Tue, 13 Dec 2011 06:09:10 +0100 5494972 http://www.medworm.com/index.php?rid=5494971&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01398.x Abstract:  There are multiple techniques and methods to assess peripheral vascular function in vivo but not without limitations. More discriminative, sensitive and also practical evaluation strategies are needed to fully characterize the peripheral vascular function. In the present work, a new quantitative descriptor, the ‘elimination half‐life time’ was developed from flow‐related variables as a non‐invasive microcirculatory rate parameter to describe vascular dynamics. Fifty‐four healthy volunteers and six type 2 diabetic patients, both genders, were submitted to a dynamical procedure consisting in the inhalation of a 100% saturated atmosphere of oxygen for 10 min. The tcpO2 and microcirculatory blood flow [Laser Doppler Flowmetry (LDF)] were measured in a randomly select... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5494971 Tue, 13 Dec 2011 06:08:55 +0100 5494971 http://www.medworm.com/index.php?rid=5494970&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01418.x (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5494970 Tue, 13 Dec 2011 06:08:43 +0100 5494970 http://www.medworm.com/index.php?rid=5476652&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01429.x AbstractThe aim was to investigate the feasibility of using iontophoresis for the cutaneous delivery of the E‐selectin antagonist CGP69669A, a sialyl Lewisx‐glycomimetic with potential activity against inflammatory skin diseases. The effects of current density and formulation on iontophoretic transport were evaluated in porcine and human skin in vitro. Cumulative permeation of CGP69669A increased with current density (69.73±9.51, 113.97±26.80 and 160.44±13.79 μg/cm2 at 0.1, 0.3 and 0.5 mA/cm2, respectively) and drug concentration (37.42±13.13, 78.96±23.13 and 160.44±13.79 μg/cm2, at 1, 3 and 5 mg/ml, respectively). In contrast, passive delivery was negligible. Although permeation from a 2% hydroxyethyl cellulose gel was lower than that from aqueous solution, skin deposition –... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5476652 Tue, 06 Dec 2011 05:00:00 +0100 5476652 http://www.medworm.com/index.php?rid=5476651&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01430.x AbstractStrains of mice vary in their susceptibility to ultra‐violet (UV) radiation‐induced skin tumors. Some strains of hairless mice (homozygous for the spontaneous Hrhr mutation) are particularly susceptible to these tumors. The skin tumors that develop in hairless mice resemble, both at the morphologic and molecular levels, UV‐induced squamous cell carcinomas (SCC) and their precursors in human. The most commonly employed hairless mice belong to the SKH1 stock. However, these mice are outbred and their genetic background is not characterized, which makes them a poor model for genetic studies. We have developed a new inbred strain from outbred SKH1 mice that we named SKHIN/Sprd (now at generation F31). In order to characterize the genetic background of this new strain, we genoty... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5476651 Thu, 01 Dec 2011 05:00:00 +0100 5476651 http://www.medworm.com/index.php?rid=5457838&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01425.x AbstractIn mammals, the skin can form complex global and local patterns to meet diverse functional requirements in different parts of the body. To date, the fundamental principles that underlie skin patterning remain poorly understood due to the involvement of multiple interacting processes. Genes involved in the planar cell polarity (PCP) signalling pathway, which is capable of polarizing cells within the planar plane of an epithelium, can control the orientation and differentiation of hair follicles, underlining their involvement in skin pattern formation. Here, we summarize recent progress that has been made to understand the PCP signalling pathway and its function in mammalian skin, including its role in hair follicle morphogenesis, ciliogenesis, and wound healing. We argue that dissec... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5457838 Thu, 01 Dec 2011 05:00:00 +0100 5457838 http://www.medworm.com/index.php?rid=5457842&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01421.x AbstractThe nervous system takes part in skin homeostasis and interacts with skin cells. In in vitro organotypic skin models, these interactions are lost due to absence of nerve endings. We have developed an in vitro organotypic skin model based on a re‐innervated human skin explant using primary sensory neurons from the dorsal root ganglia of rats. After 10 days of co‐culture between skin explant and neurons, a dense network of nerve fibres was observed. The epidermis and dermis presented nerve fibres associated with cellular body from sensory neurons introduced in the co‐culture. Epidermal thickness, cell density and quality of re‐innervated skin explant were all higher when skin explants were re‐innervated by sensory neurons at 10 days of culture. Proliferation of epidermal ce... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5457842 Tue, 29 Nov 2011 05:00:00 +0100 5457842 http://www.medworm.com/index.php?rid=5457841&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01422.x AbstractAdult stem cells could be small sources of neurons or other cellular types for regenerative medicine and tissue engineering. Recently, pluripotent stem cells have been extracted from skin tissue, which opened a new accessible source for research. To routinely obtain a high yield of functional neurons from adult human skin stem cells with defined serum‐free medium. Stem cells from abdominal skin were cultured in serum‐free medium. To differentiate them, we used a defined medium containing growth factors. Differentiated cells were identified using the following methods: 1) Oil‐red‐O staining for adipocytes, immunocytochemistry with antibodies recognising 2) neurofilaments and PGP9.5 for neural differentiation, 3) glial fibrillary acidic protein (GFAP) for glial differentiatio... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5457841 Tue, 29 Nov 2011 05:00:00 +0100 5457841 http://www.medworm.com/index.php?rid=5457840&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01423.x AbstractConsidering the clinical and genetic heterogeneity of psoriasis which may translate into distinct disease pathology and treatment response, correct typing of the main candidate gene HLA‐C is critical but not trivial. In order to facilitate genotyping, we compared established techniques with our newly developed tool. Here, we propose that typing of four single nucleotide polymorphic markers within the HLA‐C region correctly determines HLA‐Cw*06:02 genotypes in psoriatic cases and healthy controls in a population of Caucasian origin. Typing of the SNPs presented herein proved to be precise, reliable, time and cost effective and requiring low amount of DNA. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5457840 Tue, 29 Nov 2011 05:00:00 +0100 5457840 http://www.medworm.com/index.php?rid=5457839&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01424.x AbstractFor finite dose skin absorption experiments, a homogeneous donor distribution over the skin surface is usually assumed. However, the influence of the surface distribution on skin absorption is still unknown. The aim of this study was to evaluate the influence of the application area on the permeation of drugs during finite dose skin absorption experiments in static Franz diffusion cells. Permeation experiments with stained aqueous drug formulations were conducted and the application area was determined by a suitable, objective, automated computational approach.The permeation of caffeine is strongly dependent on the application area. The variability between single experiments decreased when including the application area. For the lipophilic flufenamic acid this was not the case. The... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5457839 Tue, 29 Nov 2011 05:00:00 +0100 5457839 http://www.medworm.com/index.php?rid=5422239&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01382.x In this study, we investigated the presence and activity of the recently identified absent in melanoma 2 (AIM2) inflammasome in human keratinocytes. We were able to show that an AIM2 inflammasome is active in human keratinocytes. IL‐1 production by keratinocytes plays a pivotal role in inflammatory processes in the skin. Activation of the AIM2 inflammasome in keratinocytes represents another potential trigger factor for the development and maintenance of inflammatory skin diseases. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5422239 Sat, 19 Nov 2011 05:50:50 +0100 5422239 http://www.medworm.com/index.php?rid=5422238&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01391.x Abstract:  Thymic stromal lymphopoietin (TSLP) is an interleukin‐7‐like cytokine expressed by epithelial cells and reported to be involved in allergic diseases and atopic eczema. The presence of several predicted α‐helical regions in TSPL, a structure characterizing many classical antimicrobial peptides (AMPs), prompted us to investigate whether TSLP exerts antimicrobial activities. Recombinant human TSLP exerted antimicrobial activity, particularly against Gram‐negative bacteria. Using synthetic overlapping peptide 20‐mers of TSLP, it was demonstrated that the antimicrobial effect is primarily mediated by the C‐terminal region of the protein. MKK34 (MKKRRKRKVTTNKCLEQVSQLQGLWRRFNRPLLK), a peptide spanning a C‐terminal α‐helical region in TSLP, showed potent antimicrobia... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5422238 Sat, 19 Nov 2011 05:50:39 +0100 5422238 http://www.medworm.com/index.php?rid=5422237&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01389.x Abstract:  Scalp pruritus is a common complaint that is considered a diagnostically and therapeutically challenging situation. Scalp skin has a unique neural structure that contains densely innervated hair follicles and dermal vasculature. In spite of the recent advances in our understanding of itch pathophysiology, scalp itching has not been studied as yet. In this review, we summarize the current knowledge on the neurobiology of scalp and hair follicles as well as itch mediators and provide a putative mechanism for scalp itch with special emphasis on neuroanatomy and pathophysiology. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5422237 Sat, 19 Nov 2011 05:50:27 +0100 5422237 http://www.medworm.com/index.php?rid=5422227&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01420.x AbstractAn intact keratin 5 / keratin 14 intermediate filament cytoskeleton is vital for the integrity of basal keratinocytes and for development and maintenance of epidermal structures. In epidermolysis bullosa simplex Dowling‐Meara (EBS‐DM) patients, heterozygous mutations in the keratin 14 gene in keratinocytes cause a cytoskeletal collapse leading to fragile cells susceptible to cellular stress. The primary aim of this work was to extend analysis of differentially expressed genes in an EBS‐DM model cell line to obtain insights into the molecular consequences resulting from the keratin 14 mutation. In a first step, suppression subtractive hybridization (SSH), a powerful technology to enrich for differentially expressed genes, was used to identify genes whose up‐regulation may be... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5422227 Sat, 19 Nov 2011 05:49:37 +0100 5422227 http://www.medworm.com/index.php?rid=5524865&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01419.x In this study, we demonstrate the antifibrotic effects of local administration of latency‐associated peptide (LAP), a linker propeptide that specifically converts the active form of TGF‐β1 to the inactive from, in the bleomycin (BLM)‐induced scleroderma mouse model. Histologically, co‐injection of BLM and LAP into the dorsal skin prevented proinflammatory and later sclerotic responses, features seen in mice injected with BLM alone or together with PBS as control. In addition, the skin sites co‐injected with BLM and LAP showed a marked decrease in mast cell infiltration. Isoform‐specific ELISA and real‐time RT‐PCR revealed transient decreases in connective tissue growth factor and collagen α1(I) mRNA expression 2 weeks after the co‐injection, preceded by a decrease in ... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5524865 Fri, 18 Nov 2011 05:00:00 +0100 5524865 http://www.medworm.com/index.php?rid=5504971&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01420.x Abstract:  An intact keratin 5/keratin 14 intermediate filament cytoskeleton is vital for the integrity of basal keratinocytes and for the development and maintenance of epidermal structures. In patients with epidermolysis bullosa simplex Dowling‐Meara (EBS‐DM), heterozygous mutations in the keratin 14 gene in keratinocytes cause a cytoskeletal collapse leading to fragile cells susceptible to cellular stress. The primary aim of this work was to extend analysis of differentially expressed genes in an EBS‐DM model cell line to obtain insights into the molecular consequences resulting from the keratin 14 mutation. In a first step, suppression subtractive hybridization (SSH), a powerful technology to enrich for differentially expressed genes, was used to identify genes whose up‐regul... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5504971 Fri, 18 Nov 2011 05:00:00 +0100 5504971 http://www.medworm.com/index.php?rid=5422228&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01419.x In this study, we demonstrate the anti‐fibrotic effects of local administration of latency‐associated peptide (LAP), a linker propeptide that specifically converts the active form of TGF‐β1 to the inactive from, in the bleomycin (BLM)‐induced scleroderma mouse model. Histologically, co‐injection of BLM and LAP into the dorsal skin prevented proinflammatory and later sclerotic responses, features seen in mice injected with BLM alone or together with PBS as control. In addition, the skin sites co‐injected with BLM and LAP showed a marked decrease in mast cell infiltration. Isoform‐specific ELISA and real time RT‐PCR revealed transient decreases in connective tissue growth factor (CTGF) and collagen α1(I) mRNA expression 2 weeks after the co‐injection, preceded by a decrea... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5422228 Fri, 18 Nov 2011 05:00:00 +0100 5422228 http://www.medworm.com/index.php?rid=5476657&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01415.x We report that the tetrapeptide PKEK (Pro‐Lys‐Glu‐Lys) can exert skin whitening effects based on one in vitro and four double‐blinded vehicle‐controlled in vivo studies. (i) Treatment of human keratinocytes with PKEK significantly reduced UVB‐stimulated mRNA expression of interleukin (IL)‐6, IL‐8 and TNF‐α and, most importantly, proopiomelanocorticotropin (POMC), i.e. a gene encoding the pigmentation‐inducing soluble mediator α‐ (α‐MSH). (ii) PKEK treatment significantly inhibited UVB‐induced upregulation of genes encoding for IL‐1α, IL‐6, IL‐8, TNF‐α as well as POMC and tyrosinase in 10 healthy volunteers pretreated with PKEK for 4 weeks once daily. (iii) In a study enrolling 39 Caucasian women, facial pigment spots significantly faded after 6 we... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5476657 Tue, 08 Nov 2011 05:00:00 +0100 5476657 http://www.medworm.com/index.php?rid=5476656&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01416.x Abstract:  In human skin, ultraviolet radiation (UVR)‐induced erythema is characterized by the inflammatory and angiogenic activation of dermal endothelial cells. Recently, it has been shown that the release of angiopoietin‐2 (Ang‐2) from cytoplasmic storages of activated endothelial cells is crucial for the induction of inflammation and angiogenesis. Therefore, we hypothesized that UVR exposure induces the release of Ang‐2 from endothelial cells controlling the early steps of erythema formation. In an in vivo study, suction blister fluids generated from UV‐irradiated skin showed significantly increased concentrations of Ang‐2, vascular endothelial growth factor (VEGF) and tumor necrosis factor‐α (TNFα). Likewise, in vitro UVR exposure of human dermal microvascular endoth... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5476656 Tue, 08 Nov 2011 05:00:00 +0100 5476656 http://www.medworm.com/index.php?rid=5476653&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01411.x Abstract:  The antimicrobial treatment of wounds is still a major problem. Tissue‐tolerable electrical plasma (TTP) is a new approach for topical microbial disinfection of the skin surface. The aim of the present study was to investigate the influence of TTP on a carotenoid profile in relation to skin physiology parameters (epidermal barrier function, stratum corneum (SC) hydration, surface temperature and irritation parameters). We were interested in the interaction of TTP and the antioxidative network, as well as the consequences for skin physiology parameters. These parameters are also indicative of TTP safety in vivo. For plasma application, ‘Kinpen 09’ was used (surface exposure 30–43°C) for 3 s. Beta‐carotene and water profiles were assessed by in vivo Raman microspect... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5476653 Tue, 08 Nov 2011 05:00:00 +0100 5476653 http://www.medworm.com/index.php?rid=5386858&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01411.x Conclusions:  The induction of reactive oxygen species is probably the major contributor of TTP‐efficacy in skin disinfection. Skin physiology parameters were influenced without damaging the skin or skin functions, indicating the safety of TTP under in vivo conditions. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5386858 Tue, 08 Nov 2011 05:00:00 +0100 5386858 http://www.medworm.com/index.php?rid=5386857&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01413.x AbstractUV‐induced skin cancers comprise a major problem in organ transplant recipients (OTRs). Cyclosporin A, a calcineurin inhibitor, is used as a standard immunosuppressant and clearly increases the skin cancer risk. Azathioprine does not appear to result in such an increase in skin cancer risk and mTOR inhibitors are associated with an even lesser skin cancer risk. The underlying molecular mechanisms of these clinically important differences among immunosuppressants are still unclear and may relate to other than immunological effects. Insights may be gained by the multistep skin cancer theory and xeroderma pigmentosum, where defective nucleotide excision repair (NER) results in a cellular mutator phenotype and cutaneous carcinogenesis. This viewpoint assay summarizes current knowledg... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5386857 Tue, 08 Nov 2011 05:00:00 +0100 5386857 http://www.medworm.com/index.php?rid=5386856&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01412.x AbstractAtopic eczema and psoriasis are common skin diseases. While it is well established that the pathogenesis of these diseases vary, both are characterised by impairment in epidermal barrier function and abnormal IL‐17 expression in the skin and peripheral blood. Recent findings indicated that filaggrin is essential during barrier formation and its insufficiency underlies the pathogenesis of atopic eczema. Filaggrin downregulation has also been reported in psoriasis. It is clear that Th1/Th2 bias influences expression of the protein, but an analysis of the effects of interleukin‐17 on the expression of the protein and profilaggrin processing enzymes has not yet been reported. In addition, the effect of the cytokine on components of functional epidermal barrier: tight junctions, adh... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5386856 Tue, 08 Nov 2011 05:00:00 +0100 5386856 http://www.medworm.com/index.php?rid=5386855&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01414.x Conclusion:  UVB irradiation of endogenous photosensitizers produced singlet oxygen that in turn changes the absorption of those molecules. Being an important prerequisite, the changed absorption may either reduce or increase singlet oxygen production. An increase of singlet oxygen generation may initiate a vicious cycle that has the potential to amplify UVB or UVA mediated effects in skin cells. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5386855 Tue, 08 Nov 2011 05:00:00 +0100 5386855 http://www.medworm.com/index.php?rid=5386854&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01415.x We report that the tetrapeptide PKEK (Pro‐Lys‐Glu‐Lys) can exert skin whitening effects based on one in‐vitro and four double blinded vehicle controlled in‐vivo studies:(i) Treatment of human keratinocytes with PKEK significantly reduced UVB stimulated mRNA expression of interleukin (IL)‐6, IL‐8 and TNF‐α, and, most importantly, proopiomelanocorticotropin (POMC), i.e. a gene encoding the pigmentation inducing soluble mediator α melanocyte stimulating hormone (α‐MSH). (ii) PKEK treatment significantly inhibited UVB‐induced upregulation of genes encoding for IL‐1α, IL‐6, IL‐8, TNF‐α as well as POMC and tyrosinase in 10 healthy volunteers pretreated with PKEK for 4 weeks once daily.(iii) In a study enrolling 39 Caucasian women, facial pigment spots signi... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5386854 Tue, 08 Nov 2011 05:00:00 +0100 5386854 http://www.medworm.com/index.php?rid=5386853&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01416.x AbstractIn human skin, ultraviolet radiation (UVR)‐induced erythema is characterized by the inflammatory and angiogenic activation of dermal endothelial cells. Recently, it has been shown that the release of angiopoietin‐2 (Ang‐2) from cytoplasmic storages of activated endothelial cells is crucial for the induction of inflammation and angiogenesis. Therefore, we hypothesized that UVR exposure induces the release of Ang‐2 from endothelial cells controlling the early steps of erythema formation. In an in vivo study, suction blister fluids generated from UV‐irradiated skin showed significantly increased concentrations of Ang‐2, vascular endothelial growth factor (VEGF) and tumor necrosis factor‐α (TNFα). Likewise, in vitro UVR exposure of human dermal microvascular endothelial... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5386853 Tue, 08 Nov 2011 05:00:00 +0100 5386853 http://www.medworm.com/index.php?rid=5386861&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01408.x In this study, we investigated the effect of AGEs on the production of MMP‐9 in HaCaT keratinocytes and characterized the signal transduction pathways activated by AGEs that are involved in MMP‐9 regulation. We showed that AGE‐BSA increased MMP‐9 expression in HaCaT cells at both the protein and mRNA levels. The stimulatory effect of AGE‐BSA on MMP‐9 was attenuated by inhibitors of extracellular‐signal regulated kinase (ERK1/2, U0126), p38 mitogen‐activated protein kinase (MAPK, SB203580), and NF‐κB, but not c‐Jun N‐terminal kinase. Furthermore, receptor for AGE (RAGE) was expressed in keratinocytes, and incubation with AGE‐BSA resulted in significant upregulation of RAGE expression in a dose‐dependent manner. Silencing of the RAGE gene prevented AGE‐BSA‐indu... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5386861 Fri, 04 Nov 2011 04:00:00 +0100 5386861 http://www.medworm.com/index.php?rid=5386860&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01409.x AbstractThe purpose of this study was to test the hypothesis that obese diabetic mice exhibit marked skin fragility, which is caused by increased oxidative stress and increased matrix metalloproteinase (MMP) gene expression in the subcutaneous adipose tissue. Scanning electron microscopy of skin samples from Tsumura‐Suzuki obese diabetic (TSOD) mice revealed thinner collagen bundles, and decreased density and convolution of the collagen fibers. Furthermore, skin tensile strength measurements confirmed that the dorsal skin of TSOD mice was more fragile to tensile force than that of non‐obese mice. The mRNA expressions of heme oxygenase 1 (Hmox1), a marker of oxidative stress, Mmp2 and Mmp14 were increased in the adipose tissue of TSOD mice. Antioxidant experiments were subsequently perf... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5386860 Fri, 04 Nov 2011 04:00:00 +0100 5386860 http://www.medworm.com/index.php?rid=5386859&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01410.x In conclusion, icatibant induces histamine mediated wheal and flare responses which may be reduced in severity by prophylactic administration an H1‐antihistamine. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5386859 Fri, 04 Nov 2011 04:00:00 +0100 5386859 http://www.medworm.com/index.php?rid=5386852&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01417.x Conclusion:  Our results suggest that pimecrolimus can be effective in restoring the epidermal barrier in patients with atopic dermatitis at least in part by its impact on expression of genes, which are important for the normal barrier function of skin. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5386852 Tue, 01 Nov 2011 04:00:00 +0100 5386852 http://www.medworm.com/index.php?rid=5386865&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01404.x AbstractWound infection is a form of host damage resulting from an imbalance in pathogen virulence and the host immune response. However, at present, diagnosis is based solely on bacterial numbers or inflammatory signs and is therefore not precise. Thus, infection diagnosis requires indicators of both of these factors. We focused on wound fluid because it includes both bacteria and host cells. The purpose of this study was to establish biomarkers that reflect both bacterial and host factors using the reverse transcription‐polymerase chain reaction method on the centrifugal precipitation of wound fluids (wound fluid RT‐PCR). We created full thickness wounds in animal models of the three groups: control, colonization and infection, which were conditioned by administration of different co... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5386865 Mon, 31 Oct 2011 04:00:00 +0100 5386865 http://www.medworm.com/index.php?rid=5386864&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01405.x AbstractThe non‐invasive differentiation of dermal elastic fibres from solar elastosis in vivo is of great interest in dermatologic research, especially for efficacy testing of anti‐ageing products. To date, no studies on multiphoton excited fluorescence lifetime characteristics of human elastic fibres and solar elastosis are reported.The goal of the present work was the identification of differential criteria for elastic fibres and solar elastosis by the analysis of fluorescence decay curves acquired by time‐correlated single photon counting in vivo multiphoton tomography.For this purpose, fluorescence lifetime measurements (FLIM) were performed with 47 volunteers of different age groups at sun‐protected and sun‐exposed localizations.Bi‐exponential curve fitting was applied to... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5386864 Mon, 31 Oct 2011 04:00:00 +0100 5386864 http://www.medworm.com/index.php?rid=5386863&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01406.x AbstractLipo‐PGE1 [EGLANDIN®; a lipid microsphere‐incorporated prostaglandin E1 (PGE1)] stimulates angiogenesis and promotes the healing of skin ulcers. Because the effects of Lipo‐PGE1 on cutaneous wound healing are not completely understood, we investigated the ability of Lipo‐PGE1 to affect in vivo wound healing and regulate the migration of human dermal fibroblasts (HDFs). In a murine wound model, Lipo‐PGE1 reduced the wound size compared with control mice. Lipo‐PGE1 significantly increased HDF migration in a dose‐ and time‐dependent manner. Lipo‐PGE1 markedly increased the expression of CXC chemokine receptor 4 (CXCR4), which controls the migration of HDFs, at the mRNA and protein levels. Small interfering RNA (siRNA)‐mediated knockdown of CXCR4 inhibited Lipo‐P... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5386863 Mon, 31 Oct 2011 04:00:00 +0100 5386863 http://www.medworm.com/index.php?rid=5386862&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01407.x This study suggests that dermal perivascular sites act as a niche of mesenchymal stem cells in human scalp skin, which are easily accessible and useful in regenerative medicine. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5386862 Mon, 31 Oct 2011 04:00:00 +0100 5386862 http://www.medworm.com/index.php?rid=5347637&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01403.x Conclusion:  These findings provide a new insight into the participation of C3a in the sensitization phase of CS immune responses. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5347637 Wed, 26 Oct 2011 11:42:30 +0100 5347637 http://www.medworm.com/index.php?rid=5476654&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01401.x Abstract:  The underlying mechanism of immune privilege in hair follicle cell dermal papilla (DP) and sheath (DS) populations is not well understood, and the responsiveness of hair follicle dermal cells to pro‐inflammatory challenge presently remains unknown. In this work, we describe acute NF‐κB activation in human DS, DP and dermal fibroblast (DF) cells challenged with TNF‐alpha and IL1‐beta. In contrast, the DS and DP cells revealed an unexpected tolerance to bacterial LPS challenge relative to DF cells. Understanding follicle cell responses to typical pro‐inflammatory stimuli is critical for diseases where collapse of hair follicle immune privilege is observed, and to further applications in autologous stem cell/wound healing therapeutics. (Source: Experimental Dermatology... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5476654 Mon, 24 Oct 2011 04:00:00 +0100 5476654 http://www.medworm.com/index.php?rid=5347640&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01400.x AbstractThe promise of mesotherapy is maintenance and/or recovery of a youthful skin with a firm, bright and moisturized texture. Currently applied medications employ microinjections of hyaluronic acid, vitamins, minerals and amino acids into the superficial layer of the skin. However, the molecular and cellular processes underlying mesotherapy are still elusive. Here we analyzed the effect of five distinct medication formulas on pivotal parameters involved in skin aging, i.e. collagen expression, cell proliferation, and morphological changes using normal human skin fibroblast cultures in vitro. Whereas in the presence of hyaluronic acid, NCTF135®, and NCTF135HA® cell proliferation was comparable to control cultures, however with higher expression of collagen type‐1, matrix metalloprot... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5347640 Mon, 24 Oct 2011 04:00:00 +0100 5347640 http://www.medworm.com/index.php?rid=5347639&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01401.x AbstractThe underlying mechanism of immune privilege in hair follicle cell dermal papilla (DP) and sheath (DS) populations is not well understood, and the responsiveness of hair follicle dermal cells to pro‐inflammatory challenge is presently unknown. In this work, we describe acute NF‐kappaB activation in human DS, DP and dermal fibroblast (DF) cells challenged with TNF‐alpha and IL1‐beta. By contrast the DS and DP cells revealed an unexpected tolerance to bacterial LPS challenge relative to DF cells. Understanding follicle cell responses to typical pro‐inflammatory stimuli is critical for diseases where collapse of hair follicle immune privilege is observed, and to further applications in autologous stem cell /wound healing therapeutics. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5347639 Mon, 24 Oct 2011 04:00:00 +0100 5347639 http://www.medworm.com/index.php?rid=5347638&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01402.x AbstractWhite adipose tissue is known to be involved in numerous physiological processes such as insulin‐mediated functions, lipid and glucose metabolism, vascular changes and coagulation. These processes are mainly mediated by adipokines which are secreted from either adipocytes or cells of the stromal‐vascular fraction of adipose tissue.In obesity a shift in the production of adipokines can mediate the development of associated diseases such as metabolic syndrome and vascular complications such as artherosclerosis, myocardial infarction or stroke which are known comorbidities of psoriasis, too.As obesity is a frequently seen comorbidity in psoriasis patients, adipokines could be involved in the pathogenesis of psoriasis and/or its comorbidities either dependently or independently fro... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5347638 Mon, 24 Oct 2011 04:00:00 +0100 5347638 http://www.medworm.com/index.php?rid=5335931&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01399.x In this study, we investigated the 1) ROS production, 2) potential sites of ROS production, 3) expression of cell surface molecules, 4) secretion of cytokines, 5) and ROS‐dependent protein carbonylation in chemical‐treated HaCaT cells. Treatment of HaCaT cells with 2,4‐dinitrochlorobenzene (DNCB) and benzalkonium chloride (BKC) increased ROS levels in a time and dose‐dependent manner, as determined with dichlorodihydrofluorescein diacetate (CM‐H2DCFDA), without reducing cell viability. Potential sources of ROS production were evaluated with pre‐treatment of diphenylene iodonium (DPI), an inhibitor of NADPH oxidase; rotenone, an inhibitor of the mitochondrial electron transport chain complex; or allopurinol, a xanthine oxidase inhibitor. DNCB‐induced ROS was related to both ... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5335931 Sat, 22 Oct 2011 04:56:15 +0100 5335931 http://www.medworm.com/index.php?rid=5476655&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01399.x In this study, we investigated the (i) ROS production; (ii) potential sites of ROS production; (iii) expression of cell surface molecules; (iv) secretion of cytokines; and (v) ROS‐dependent protein carbonylation in chemical‐treated human keratinocyte cell line (HaCaT) cells. Treatment of HaCaT cells with 2,4‐dinitrochlorobenzene (DNCB) and benzalkonium chloride (BKC) increased ROS levels in a time‐ and dose‐dependent manner, as determined with dichlorodihydrofluorescein diacetate (CM‐H2DCFDA), without reducing cell viability. Potential sources of ROS production were evaluated with pretreatment of diphenylene iodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; rotenone, an inhibitor of the mitochondrial electron transport chain complex or... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5476655 Fri, 21 Oct 2011 04:00:00 +0100 5476655 http://www.medworm.com/index.php?rid=5335932&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01398.x AbstractThere are multiple techniques and methods to assess peripheral vascular function in vivo but not without limitations. More discriminative, sensitive and also practical evaluation strategies are needed to fully characterize the peripheral vascular function. In the present work, a new quantitative descriptor the “elimination half‐life time” was developed from flow related variables as a non‐invasive microcirculatory rate parameter to describe vascular dynamics. 54 healthy volunteers and 6 type 2 diabetic patients, both genders, were submitted to a dynamical procedure consisting in the inhalation of a 100% saturated atmosphere of oxygen for 10 minutes. TcpO2 and microcirculatory blood flow (LDF) were measured in a randomly selected leg with a Periflux 5000 system before, durin... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5335932 Fri, 21 Oct 2011 04:00:00 +0100 5335932 http://www.medworm.com/index.php?rid=5324085&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01396.x AbstractThe effects of the histamine H4 receptor antagonist JNJ7777120 were evaluated in a model of acute skin inflammation induced by local application of croton oil. The influence of strain on the effect of JNJ7777120 was investigated in four different mouse strains (CD‐1, NMRI, BALB/c and C57BL/6J). In CD‐1 mice JNJ777720 (30‐100 mg/kg subcutaneously, s.c.) exerted a dose‐dependent inhibition of croton oil‐induced ear inflammation and polymorphonuclear leukocyte infiltration, as confirmed by histological evaluation of ear tissues. JNJ7777120 (30‐100 mg/kg) did not reduce ear edema in NMRI, BALB/c or C57BL/6J mice. The positive control, dexamethasone (2 mg/kg s.c.) induced significant antiinflammatory effects only in CD‐1 and NMRI mice. In these strains also the histamine H... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5324085 Tue, 18 Oct 2011 05:09:36 +0100 5324085 http://www.medworm.com/index.php?rid=5324086&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01397.x AbstractPrevious studies have reported that repeated solar and artificial UVB (280‐320 nm) and UVA (320‐400 nm) exposuresan modify acquired melanocytic nevi (AMN). We therefore investigated the clinical, dermoscopic, histological and immunohistochemical changes of AMN exposed to UVB and UVA radiation. Twenty healthy volunteers with at least 3 AMN on the trunk were enrolled in the present study and randomised into two groups to receive equally effective doses of narrow‐ band (NB)‐UVB or UVA1. Three exposures per week were delivered for a total of four weeks. During exposures, one AMN was left unprotected, a second one was shielded with an opaque adhesive tape and the third nevus was covered with a commercial sunscreen. After the irradiation cycle, the AMN were surgically removed and... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5324086 Mon, 17 Oct 2011 04:00:00 +0100 5324086 http://www.medworm.com/index.php?rid=5314592&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01365.x In conclusion, Chk1 and FANCD2 function downstream of ATR in a non‐redundant manner for the establishment and maintenance of psoralen photoactivation‐induced senescence. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5314592 Sat, 15 Oct 2011 05:07:55 +0100 5314592 http://www.medworm.com/index.php?rid=5408186&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01384.x Abstract:  Tumor necrosis factor (TNF)‐α is known to play a pivotal role in the pathogenesis of psoriasis. TNF‐α has been shown to act directly on keratinocytes, thereby inducing the production of various kinds of chemokines, which contributes to the infiltration of leucocytes into the psoriatic lesions. Recent studies have shown that both interleukin (IL)‐17 and IL‐27 are increased in psoriatic lesional tissue. However, the interactions between TNF‐α, IL‐17 and IL‐27 in chemokine production by keratinocytes have not been fully elucidated. Here, we examined in human keratinocytes how TNF‐α, IL‐17 and IL‐27 affect production of chemokines that are involved in the pathogenesis of psoriasis. We found that IL‐17 and IL‐27 exert opposite effects on TNF‐α‐media... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5408186 Tue, 11 Oct 2011 04:00:00 +0100 5408186 http://www.medworm.com/index.php?rid=5408185&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01390.x In this study, we stimulated primary keratinocytes with the TLR3‐ligand polyI:C. This induced a toxic effect shown by up‐regulation of the alarmin high‐mobility group protein B1 and reduced responses in a MTT‐assay. PolyI:C was a potent inducer of proinflammatory cytokines, and both these responses and the cytotoxic effects were found to be TLR3 dependent, as demonstrated by the use of siRNA for TLR3. Interestingly, co‐stimulation with oligodeoxynucleotides (ODNs) inhibited all polyI:C induced effects. This inhibition was found to be mediated by the competition of endocytic uptake of polyI:C and ODNs. We have found polyI:C induced cytotoxicity and proinflammatory responses to be dependent of TLR3 and that this may be inhibited by ODNs. With these findings, we see a promising pote... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5408185 Tue, 11 Oct 2011 04:00:00 +0100 5408185 http://www.medworm.com/index.php?rid=5408184&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01392.x In conclusion, CRABP‐II and FABP5 expression were imbalanced in ATRA‐resistant COLO 16 cells. 5‐Aza‐enhanced CRABP‐II expression and unmethylation in CRABP‐II promoter region suggest the methylation of certain CRABP‐II regulatory gene(s) in COLO 16 cells. As neither restoration of CRABP‐II expression nor the increased CRABP‐II versus FABP5 ratio can overcome ATRA resistance of COLO 16 cells, additional ATRA‐resistant mechanism(s) may present in human c‐SCCs and COLO 16 cells would be of value in addressing this issue. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5408184 Tue, 11 Oct 2011 04:00:00 +0100 5408184 http://www.medworm.com/index.php?rid=5304519&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01384.x AbstractTNF‐α is known to play a pivotal role in the pathogenesis of psoriasis. TNF‐α has been shown to act directly on keratinocytes, thereby inducing the production of various kinds of chemokines, which contributes to the infiltration of leukocytes into the psoriatic lesions. Recent studies have shown that both IL‐17 and IL‐27 are increased in psoriatic lesional tissue. However, the interactions between TNF‐α, IL‐17 and IL‐27 in chemokine production by keratinocytes have not been fully elucidated. Here, we examined in human keratinocytes how TNF‐α, IL‐17 and IL‐27 affect production of chemokines that are involved in the pathogenesis of psoriasis. We found that IL‐17 and IL‐27 exert opposite effects on TNF‐α‐mediated chemokine production. This suggests tha... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5304519 Tue, 11 Oct 2011 04:00:00 +0100 5304519 http://www.medworm.com/index.php?rid=5304518&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01385.x AbstractSelection for targeted therapies in melanoma is currently based on the search for mutations in selected genes. We aimed at evaluating the interest of signalling and chemosensitivity studies in addition to genotyping for assessing the best suitable treatment in an individual patient. We extracted genomic DNA and melanoma cells from tumor tissue of a skin metastasis of a 17 year‐old woman with stage IV melanoma progressing despite 3 successive lines of treatment. Despite the absence of mutation in BRAF, NRAS cKIT, the MPAK pathway was activated and a significant response to sorafenib, a mitogen‐activated protein kinase (MAPK)/RAF inhibitor, was found in signaling and chemosensitivity assays. A treatment combining sorafenib and dacarbazine produced a partial response for 9 months,... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5304518 Tue, 11 Oct 2011 04:00:00 +0100 5304518 http://www.medworm.com/index.php?rid=5304517&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01386.x AbstractGiven that metastasized melanoma is a fatal disease in most cases, it is tempting to develop strategies to a priori prevent metastasis. We have stimulated the pulmonary innate immune system by macrophage‐activating lipopeptide‐2 (MALP‐2), a specific agonist at toll‐like receptor (TLR) 2/6, and investigated its impact on experimental melanoma metastasis. In C57BL/6 mice, intratracheal application of MALP‐2 induced a profound influx of neutrophils and macrophages into the lung, which peaked after 24h (6‐fold increase) and returned to baseline within 72h. Further analysis revealed that MALP‐2 also markedly induced VCAM‐1 expression on pulmonary blood vessels. In vitro experiments demonstrated that this adhesion molecule mediates binding of B16F10 melanoma cells. Furthe... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5304517 Tue, 11 Oct 2011 04:00:00 +0100 5304517 http://www.medworm.com/index.php?rid=5304516&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01387.x We describe a novel GLMN mutation in an Italian family with GVM in which some members present with the less commonly observed phenotype of solitary lesions. A second somatic “hit” mutation in GLMN was not discovered in our family. We further provide histological, immunohistochemical, and electron microscopic data exhibiting the classic features of GVM. The diagnosis of GVM is critical due to distinction from venous malformations and blue rubber bleb nevus syndrome, which may demonstrate clinical similarities but require different treatment. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5304516 Tue, 11 Oct 2011 04:00:00 +0100 5304516 http://www.medworm.com/index.php?rid=5304515&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01388.x AbstractCentella asiatica (C. asiatica) is a pharmacological plant in South Asia. It has been demonstrated that C. asiatica extracts containing various pentacyclic triterpenes exert healing effects, especially wound healing and collagen synthesis in skin. However, there are few studies on the effect of C. asiatica extracts on stress‐induced premature senescence (SIPS). To determine whether H2O2‐induced senescence is affected by C. asiatica extracts we performed senescence analysis on cultured human dermal fibroblasts (HDFs). We also analysed whole gene expression level using microarrays and showed that 39 mRNAs are differentially expressed in H2O2‐induced HDFs with and without treatment with C. asiatica extracts. These genes regulate apoptosis, gene silencing, cell growth, transcript... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5304515 Tue, 11 Oct 2011 04:00:00 +0100 5304515 http://www.medworm.com/index.php?rid=5304514&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01389.x AbstractScalp pruritus is a common complaint that is considered a diagnostically and therapeutically challenging situation. Scalp skin has a unique neural structure that contains densely innervated hair follicles and dermal vasculature. In spite of the recent advances in our understanding of itch pathophysiology, scalp itching has not been studied as yet. In this review, we summarize the current knowledge on the neurobiology of scalp and hair follicles as well as itch mediators and provide a putative mechanism for scalp itch with special emphasis on neuroanatomy and pathophysiology. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5304514 Tue, 11 Oct 2011 04:00:00 +0100 5304514 http://www.medworm.com/index.php?rid=5304513&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01390.x In this study we stimulated primary keratinocytes with the TLR3‐ligand polyI:C. This induced a toxic effect shown by up‐regulation of the alarmin high mobility group protein B1 and reduced responses in a MTT‐assay. PolyI:C was a potent inducer of proinflammatory cytokines, and both these responses and the cytotoxic effects were found to be TLR3 dependent, as demonstrated by the use of siRNA for TLR3. Interestingly, co‐stimulation with oligodeoxynucleotides (ODNs) inhibited all polyI:C induced effects. This inhibition was found to be mediated by competition of endocytic uptake of polyI:C and ODNs.We have found polyI:C induced cytotoxicity and proinflammatory responses to be dependent of TLR3, and that this may be inhibited by ODNs. With these findings we see a promising potential fo... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5304513 Tue, 11 Oct 2011 04:00:00 +0100 5304513 http://www.medworm.com/index.php?rid=5304512&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01391.x Conclusion  We here describe a novel antimicrobial role for TSLP. The antimicrobial activity is primarily mediated by the C‐terminal part of the protein. In combination with the previously known cytokine function of TSLP, our result indicates dual functions of the molecule and a previously unknown role in host defense. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5304512 Tue, 11 Oct 2011 04:00:00 +0100 5304512 http://www.medworm.com/index.php?rid=5304511&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01392.x In conclusion, CRABP‐II and FABP5 expression were imbalanced in ATRA‐resistant COLO 16 cells. 5‐Aza‐enhanced CRABP‐II expression and unmethylation in CRABP‐II promoter region suggest the methylation of certain CRABP‐II regulatory gene(s) in COLO 16 cells. Since neither restoration of CRABP‐II expression nor the increased CRABP‐II versus FABP5 ratio can overcome ATRA resistance of COLO 16 cells, additional ATRA resistant mechanism(s) may present in human c‐SCCs and COLO 16 cells would be of value in addressing this issue. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5304511 Tue, 11 Oct 2011 04:00:00 +0100 5304511 http://www.medworm.com/index.php?rid=5304510&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01393.x This article provides a review of the basic concepts and players of the innate immune system and will present some of the newer data defining the innate immune networks effectively regulating the immune homeostasis and immune effector mechanisms with special focus on the skin as one of the organs involved in regulating the immune interface between the environment and the organism. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5304510 Tue, 11 Oct 2011 04:00:00 +0100 5304510 http://www.medworm.com/index.php?rid=5304509&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01394.x AbstractWe assessed the ability of ebselen, a glutathione peroxidase mimic, to reduce pigmentation in various models. In murine B16 melanocytes, 25 μM ebselen inhibited melanogenesis and induced a depolymerisation of actin filaments. In co‐cultures of B16 melanocytes with BDVII keratinocytes, a pre‐treatment of melanocytes with ebselen resulted in a strong inhibition of melanosome transfer to keratinocytes, as shown under optical and electron microscopy. In reconstructed epidermis, topical 0.5% ebselen led to a 2‐fold decrease of melanin without affecting the density of active melanocytes. A similar result was obtained with topical 0.5% ebselen in black guinea pig ears. Ebselen induced a decrease of epidermal melanin parallel to a localisation of melanin and melanosomes in the basal... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5304509 Tue, 11 Oct 2011 04:00:00 +0100 5304509 http://www.medworm.com/index.php?rid=5304521&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01382.x In this study we investigated the presence and activity of the recently identified AIM2 inflammasome in human keratinocytes. We were able to show that an AIM2 inflammasome is active in human keratinocytes. IL‐1 production by keratinocytes plays a pivotal role in inflammatory processes in the skin. Activation of the AIM2 inflammasome in keratinocytes represents another potential trigger factor for the development and maintenance of inflammatory skin diseases. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5304521 Mon, 10 Oct 2011 04:00:00 +0100 5304521 http://www.medworm.com/index.php?rid=5304520&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01383.x AbstractHuman skin equivalents (SEs) are popular 3‐dimensional (D) cell culture systems in fundamental and applied dermatology. They have been made to contain dendritic cells, but so far no study on the incorporation of potentially anti‐inflammatory dermal macrophages has been performed. Here we show that monocyte‐derived dermal‐type macrophages, can be introduced into a rigid scaffold with dermal fibroblasts. They maintain their cell surface markers CD163, DC‐SIGN/CD209 and HLA‐DR, which discriminates them from monocytes and dendritic cells. They retain the ability to produce the anti‐inflammatory cytokine IL‐10 in response to LPS and to phagocytose latex beads. We thus demonstrate the feasibility of creating macrophage‐fibroblast 3D cultures, as a first step towards gen... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5304520 Mon, 10 Oct 2011 04:00:00 +0100 5304520 http://www.medworm.com/index.php?rid=5304508&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01395.x AbstractDespite recent developments there is a high medical need for new treatment options for chronic inflammatory dermatoses like allergic contact dermatitis (ACD) and psoriasis. Particularly more predictive skin inflammation models are required to facilitate the process of drug discovery.Murine contact hypersensitivity (CHS) models adequately reflect ACD and are also used to characterize therapeutic approaches for psoriasis. Using the hapten 2,4‐dinitrofluorobenzene (DNFB) we established new subacute and subchronic DNFB‐induced CHS models in C57BL/6 mice, which more closely reflect the characteristics of chronic T cell‐dependent inflammatory dermatoses as pronounced keratinocyte proliferation, strong hypervascularization, immune cell infiltration and overexpression of T helper cel... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5304508 Sat, 01 Oct 2011 04:00:00 +0100 5304508 http://www.medworm.com/index.php?rid=5237847&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01352.x (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5237847 Thu, 22 Sep 2011 07:05:46 +0100 5237847 http://www.medworm.com/index.php?rid=5237846&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01348.x (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5237846 Thu, 22 Sep 2011 07:05:45 +0100 5237846 http://www.medworm.com/index.php?rid=5237845&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01363.x (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5237845 Thu, 22 Sep 2011 07:05:15 +0100 5237845 http://www.medworm.com/index.php?rid=5314590&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01380.x Abstract:  Tobacco smoke is known to be an element contributing to accelerate premature skin ageing. Cysteine‐rich 61 (Cyr61) is a member of the connective tissue factor CCN (Cyr61, CTGF and Nov) family, and early growth response‐1 (Egr‐1) is a generally expressed member of the zinc‐finger family of transcription factors. To investigate the regulatory potential of Egr‐1 on expression of Cyr61 by smoking, this study examined the hypothesis that cigarette smoke‐induced Egr‐1 induces expression of Cyr61 in human skin dermal fibroblasts (HSDF). HSDF were exposed to different concentrations of cigarette smoke extract (CSE) for 24 h; a cytotoxicity assay was then performed for the detection of cell proliferation. Results of Western blot and reverse transcription‐polymerase ch... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5314590 Tue, 06 Sep 2011 04:00:00 +0100 5314590 http://www.medworm.com/index.php?rid=5314589&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01381.x Abstract:  To define the potential involvement of polymorphisms in the 3′untranslated region (3′UTR) of the prostaglandin synthetase‐2 (PTGS‐2) gene to non‐melanoma skin cancer (NMSC) predisposition after transplantation, we screened for genetic variant, relevant parts of this region. It contains binding sites for trans‐acting factors, an alternative polyadenylation site and putative target sequences for miRNAs. Variant +8473T>C did not appear to play a functional role in the regulation of gene expression in human keratinocyte‐transfected cells. In addition to the well‐known +8473T>C, we identified four polymorphisms: +8293G>C, +10259T>G, +10267G>A and +10335G>A. No allele frequency differences were observed between cases and controls neither for +8473T&... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5314589 Tue, 06 Sep 2011 04:00:00 +0100 5314589 http://www.medworm.com/index.php?rid=5196557&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01380.x AbstractTobacco smoke is known to be an element contributing to accelerated premature skin aging. Cysteine‐rich 61 (Cyr61) is a member of the connective tissue factor CCN (Cyr61, CTGF, and Nov) family and early growth response‐1 (Egr‐1) is a generally expressed member of the zinc‐finger family of transcription factors. To investigate the regulatory potential of Egr‐1 on expression of Cyr61 by smoking, this study examined the hypothesis that cigarette smoke‐induced Egr‐1 induces expression of Cyr61 in human skin dermal fibroblasts (HSDF).HSDF were exposed to different concentrations of cigarette smoke extract (CSE) for 24 hours; a cytotoxicity assay was then performed for detection of cell proliferation. Results of Western blot and reverse transcription‐polymerase chain reac... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5196557 Mon, 05 Sep 2011 23:00:00 +0100 5196557 http://www.medworm.com/index.php?rid=5314591&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01379.x In this study, we found that PD significantly inhibited melanin synthesis at low concentrations. These effects were further demonstrated by the PD‐induced inhibition of cAMP production, phosphorylation of the cAMP‐response element‐binding protein and expression of microphthalmia‐associated transcription factor and its downstream genes, tyrosinase, tyrosinase‐related proteins‐1 and Dct/tyrosinase‐related proteins‐2, suggesting that PD inhibits melanogenesis through the downregulation of cAMP signalling. Furthermore, PD induced significant morphological changes in melanocytes, namely, the retraction of dendrites. A small GTPase assays revealed that PD stimulated an increase in GTP‐bound Rho content, one of downstream molecules of cAMP, but not in Rac or CDC42 content. Moreo... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5314591 Sat, 03 Sep 2011 04:00:00 +0100 5314591 http://www.medworm.com/index.php?rid=5314587&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01377.x Abstract:  The coincidence of skin tumors and elevated mast cell (MC) numbers has been known for many years. However, it has remained controversial whether, in this context, MCs promote or inhibit tumor growth. Addressing this problem, different melanoma and squamous cell carcinoma cell lines were co‐cultivated with primary, dermal MC for 24 h and gene or protein expression of cytokines tumor necrosis factor (TNF‐α), interleukin‐6 (IL‐6) and interleukin‐8 (IL‐8) estimated. Co‐culture with MCs led to an increase in IL‐8 gene expression and IL‐8 protein release from melanoma cells and IL‐6 and IL‐8 gene expression and protein release from squamous cell carcinoma cells, respectively. Moreover induction of IL‐6 and IL‐8 was primarily regulated by MC‐derived TNF... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5314587 Sat, 03 Sep 2011 04:00:00 +0100 5314587 http://www.medworm.com/index.php?rid=5184135&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01377.x AbstractThe coincidence of skin tumours and elevated mast cell (MC) numbers has been known for many years. However, it has remained controversial whether in this context MCs promote or inhibit tumour growth.Addressing this problem, different melanoma and squamous cell carcinoma cell lines were co‐cultivated with primary, dermal MC for 24 hours, and gene or protein expression of cytokines tumour necrosis factor (TNFα), interleukin‐6 (IL‐6) and interleukin‐8 (IL‐8) estimated.Co‐culture with MCs led to an increase in IL‐8 gene expression and IL‐8 protein release from melanoma cells and IL‐6 and IL‐8 gene expression and protein release from squamous cell carcinoma cells, respectively. Moreover induction of IL‐6 and IL‐8 was primarily regulated by MC‐derived TNF‐α.... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5184135 Fri, 02 Sep 2011 23:00:00 +0100 5184135 http://www.medworm.com/index.php?rid=5184134&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01378.x This study suggests that, compared to pemphigus, BP shows more Th17 cell‐related inflammation and less Treg‐related regulation. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5184134 Fri, 02 Sep 2011 23:00:00 +0100 5184134 http://www.medworm.com/index.php?rid=5196556&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01381.x AbstractTo define the potential involvement of polymorphisms in the 3′Untranslated Region (3′UTR) of the prostaglandin syntethase‐2 (PTGS‐2) gene to non‐melanoma skin cancer (NMSC) predisposition after transplantation, we screened for genetic variants relevant parts of this region. It contains binding sites for trans‐acting factors, an alternative polyadenylation site, and putative target sequences for miRNAs.Variant +8473T>C did not appear to play a functional role in the regulation of gene expression in human keratinocytes (HaCat) transfected cells. In addition to the well‐known +8473T>C, we identified four polymorphisms: +8293G>C, +10259T>G, +10267G>A and +10335G>A. No allele frequency differences were observed between cases and controls neither for +8473... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5196556 Wed, 31 Aug 2011 23:00:00 +0100 5196556 http://www.medworm.com/index.php?rid=5184133&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01379.x In this study, we found that PD significantly inhibited melanin synthesis at low concentrations. These effects were further demonstrated by the PD‐induced inhibition of cAMP production, phosphorylation of the CRE binding protein (CREB) and expression of microphthalmia‐associated transcription factor (MITF) and its downstream genes, tyrosinase, Tyrp‐1 and Dct/Tyrp‐2, suggesting that PD inhibits melanogenesis through the downregulation of cAMP signaling. Furthermore, PD induced significant morphological changes in melanocytes, namely, the retraction of dendrites. A small GTPase assays revealed that PD stimulated an increase in GTP‐bound Rho content, one of downstream molecules of cAMP, but not in Rac or CDC42 content. Moreover, a Rho inhibitor (C3 exoenzyme) and a Rho kinase inhibi... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5184133 Wed, 31 Aug 2011 23:00:00 +0100 5184133 http://www.medworm.com/index.php?rid=5175895&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01376.x AbstractAlthough fumaric acid esters (FAE) have a decade‐long firm place in the therapeutic armamentarium for psoriasis, their pleiotropic mode of action is not yet fully understood. While most previous studies have focused on the effects of FAE on leukocytes, we have addressed their activity on macro‐ and microvascular endothelial cells.As detected both on mRNA and protein levels, dimethylfumarate effected a profound reduction of TNFα‐induced expression of E‐selectin (CD62E), ICAM‐1 (CD54) and VCAM‐1 (CD106) on two different endothelial cell populations in a concentration‐dependent manner. Other endothelial surface receptors including P‐selectin (CD62P), PECAM‐1 (CD31) and CD144 were not affected by DMF, even at concentrations as high as 200 μM.This reduction of severa... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5175895 Tue, 30 Aug 2011 14:56:50 +0100 5175895 http://www.medworm.com/index.php?rid=5314588&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01375.x Abstract:  PCR‐based clonality assay of rearranged T‐cell receptor genes gamma and beta (TCRG and TCRB) in a number of cases could be essential to discriminate between cutaneous T‐cell lymphomas and reactive lymphoproliferative lesions in the skin. However, extraction of good‐quality DNA from skin specimens (especially formalin‐fixed paraffin‐embedded) remains a challenge. Common procedures, being labour‐intensive and time‐consuming and requiring toxic solvents such as phenol and chloroform, still may end up with DNA sample of insufficient quality. We herewith present a simple and efficient method for DNA isolation based on ammonia extraction of tissue, followed by neutralization and simultaneous salting out of proteins with acetic acid. We have analysed 30 samples – 24... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5314588 Mon, 29 Aug 2011 04:00:00 +0100 5314588 http://www.medworm.com/index.php?rid=5175898&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01374.x AbstractHand dermatitis describes inflammatory skin condition localized to the hands. Nurses working at hospital settings are prone to develop hand dermatitis. The current study aimed to evaluate if certain genetic polymorphisms were associated with development of atopic eczema or non‐atopic hand dermatitis in Taiwanese population. Nurses of Kaohsiung Medical University Hospital were recruited. Atopic eczema, non‐atopic hand dermatitis, and normal control groups were identified. The serine protease inhibitor Kazal type 5 (SPINK5), filaggrin, and interleukin‐31 (IL‐31) gene variants were compared between the diseased and control groups. Our results showed that rs2303070 T allele of SPINK5 (assuming recessive model; OR=3.58, 95% CI 1.63‐7.84; p=0.0014) and rs7977932 G allele of IL�... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5175898 Sun, 28 Aug 2011 23:00:00 +0100 5175898 http://www.medworm.com/index.php?rid=5175896&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01375.x AbstractPCR‐based clonality assay of rearranged T‐cell receptor genes gamma and beta (TCRG and TCRB) in a number of cases could be essential to discriminate between cutaneous T‐cell lymphomas and reactive lymphoproliferative lesions in the skin. However, extraction of good quality DNA from skin specimens (especially formalin fixed paraffin embedded) remains a challenge. Common procedures being labor intensive, time consuming and requiring toxic solvents like phenol and chloroform, still may end up with DNA sample of insufficient quality. We herewith present a simple and efficient method of DNA isolation based on ammonia extraction of tissue, followed by neutralization and simultaneous salting out of proteins with acetic acid. We have analyzed 30 samples ‐ 24 fresh (16 skin, 2 splee... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5175896 Sun, 28 Aug 2011 23:00:00 +0100 5175896 http://www.medworm.com/index.php?rid=5143965&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01367.x Abstract:In psychophysical experiments, humans use different verbal responses to pruritic and algesic chemical stimuli to indicate the different qualities of sensation they feel. A major challenge for behavioral models in the mouse of chemical itch and pain in humans is to devise experimental protocols that provide the opportunity for the animal to exhibit a multiplicity of responses as well. One basic criterion is that chemicals that evoke primarily itch or pain in humans should elicit different types of responses when applied in the same way to the mouse. Meeting this criterion is complicated by the fact that the type of behavioral responses exhibited by the mouse depends in part on the site of chemical application such as the nape of the neck which evokes only scratching with the hind p... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5143965 Sat, 20 Aug 2011 15:42:26 +0100 5143965 http://www.medworm.com/index.php?rid=5335933&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01364.x In this study, we investigated whether a long‐standing hyperglycaemic condition including type 2 DM impairs skin barrier homoeostasis in proportion to the duration and its pathomechanism. We utilized the Otsuka Long‐Evans Tokushima Fatty (OLETF) rats as an animal model of long‐standing hyperglycaemia and Long‐Evans Tokushima Otsuka rats as a control strain. We confirmed that a long‐standing hyperglycaemia delayed skin barrier homoeostasis, which correlated with haemoglobin A1c levels. OLETF rats as a long‐standing hyperglycaemia model exhibited decreased epidermal lipid synthesis and antimicrobial peptide expression with increasing age. Decreased epidermal lipid synthesis accounted for decreased lamellar body production. In addition, OLETF rats had significantly higher serum le... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5335933 Wed, 17 Aug 2011 04:00:00 +0100 5335933 http://www.medworm.com/index.php?rid=5143968&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01364.x Conclusions/interpretation:  A long‐standing hyperglycemic condition impairs skin barrier function including permeability and antimicrobial barriers by accelerating skin aging process in proportion to the duration of hyperglycemia, which could be a major pathophysiology underlying cutaneous complications of DM. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5143968 Tue, 16 Aug 2011 23:00:00 +0100 5143968 http://www.medworm.com/index.php?rid=5143967&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01365.x In conclusion, Chk1 and FANCD2 function downstream of ATR in a non‐redundant manner for the establishment and maintenance of psoralen photoactivation‐induced senescence. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5143967 Tue, 16 Aug 2011 23:00:00 +0100 5143967 http://www.medworm.com/index.php?rid=5143966&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01366.x In this study, mouse epithelial cells (MECs) and mouse dermal cells (MDCs) were grafted onto the dorsal skin of nude mice using the chamber, flap, or patch assays. Comparisons were conducted based upon gross, scanning electron microscopic, and histological observations. MDCs alone induced hair follicle reconstitution with production of hairs yielding false‐positive results caused by contamination by hair follicle remnants. Neither primary MECs nor cultured MDCs alone formed hair follicles but did result in hair follicle formation when mixed together. Frozen MECs or MDCs resulted in decreased hair follicle inductive activity but could still regenerate hairs. The hair patch assay was the quickest model (20±3 days) to determine if cell mixtures would reconstitute hair follicles that produc... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5143966 Tue, 16 Aug 2011 23:00:00 +0100 5143966 http://www.medworm.com/index.php?rid=5126430&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01362.x AbstractEstrogen (17β estradiol) and the dietary antioxidants resveratrol, genistein and S‐equol, an isoflavone produced from the gut biotransformation of soy daidzein, are effective agents to reduce aging in skin. It is widely held that these antioxidants scavenge free radicals to prevent skin damage. However, the evidence to date suggest that the primary mechanism of action of these antioxidants is to activate estrogen receptor β (ERβ), which in turn enhances the expression of antioxidant enzymes and inhibits the expression of Snail, a transcription factor that regulates keratinocyte cell proliferation and migration. Based on their selectivity, ERβ agents provide a treatment option for aging skin without the potential safety issues associated with estrogen therapy. (Source: Experim... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5126430 Sun, 14 Aug 2011 00:05:29 +0100 5126430 http://www.medworm.com/index.php?rid=5119949&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01349.x (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5119949 Fri, 12 Aug 2011 16:58:21 +0100 5119949 http://www.medworm.com/index.php?rid=5119948&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01338.x Abstract:  Adult stem cells in rapidly renewing tissues have been classically defined as rare, relatively quiescent cells with the unique capacity to constantly self‐renew and regenerate tissues during homeostasis. Although this view remains firmly embedded in the skin field, particularly in the area of hair follicle stem cell biology, it has been challenged by a number of notable publications in 2007. These papers leave an uncomfortable feeling with the reader if one believes that stem cells and transit amplifying cells are two polar opposites and ‘never the twain shall meet.’ Even if you do not subscribe to this extreme view, the implications appear to be far‐reaching given that the majority of techniques devised for stem cell identification have used the fundamental tenet that... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5119948 Fri, 12 Aug 2011 16:57:52 +0100 5119948 http://www.medworm.com/index.php?rid=5225712&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01362.x Abstract:  Oestrogen (17β estradiol) and the dietary antioxidants resveratrol, genistein and S‐equol, an isoflavone produced from the gut biotransformation of soy daidzein, are effective agents to reduce ageing in skin. It is widely held that these antioxidants scavenge free radicals to prevent skin damage. However, the evidence to date suggests that the primary mechanism of action of these antioxidants is to activate oestrogen receptor β (ERβ), which in turn enhances the expression of antioxidant enzymes and inhibits the expression of snail, a transcription factor that regulates keratinocyte cell proliferation and migration. Based on their selectivity, ERβ agents provide a treatment option for ageing skin without the potential safety issues associated with oestrogen therapy. (Sour... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5225712 Fri, 12 Aug 2011 04:00:00 +0100 5225712 http://www.medworm.com/index.php?rid=5126431&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01361.x This study investigated if sweat glands were hypertrophied in axillary hyperhidrotic patients and if mechanisms associated with fluid transport were found in all types of axillary sweat glands. The occurrence of apoeccrine sweat glands was also investigated. Axillary skin biopsies from control and hyperhidrosis patients were examined using immunohistochemistry, image analysis and immunofluorescence microscopy. Results showed that glands were not hypertrophied, and that only the clear cells in the eccrine glands expressed proteins associated with fluid transport. There was no evidence of the presence of apoeccrine glands in the tissues investigated. Preliminary findings suggest the eccrine gland secretory clear cell as the main source of fluid transport in hyperhidrosis. (Source: Experiment... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5126431 Thu, 11 Aug 2011 23:00:00 +0100 5126431 http://www.medworm.com/index.php?rid=5225713&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01359.x Abstract:  Hailey–Hailey disease (HHD) is an autosomal dominant disorder characterized by suprabasal cutaneous cell separation (acantholysis) leading to the development of erosive and oozing skin lesion. Micro RNAs (miRNAs) are endogenous post‐transcriptional modulators of gene expression with critical functions in health and disease. Here, we evaluated whether the expression of specific miRNAs may play a role in the pathogenesis of HHD. Here, we report that miRNAs are expressed in a non‐random manner in Hailey–Hailey patients. miR‐125b appeared a promising candidate for playing a role in HHD manifestation. Both Notch1 and p63 are part of a regulatory signalling whose function is essential for the control of keratinocyte proliferation and differentiation and of note, the expres... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5225713 Sat, 06 Aug 2011 04:00:00 +0100 5225713 http://www.medworm.com/index.php?rid=5196558&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01360.x Abstract:  To elucidate the possible involvement of nitric oxide (NO) derived from inducible NO synthase (iNOS) in the pathogenesis of patients with allergic rhinitis, we used an animal model of atopic dermatitis (AD) induced by epicutaneous sensitization and analysed the differences in ear thickness, the frequency of scratching and plasma levels of ovalbumin‐specific immunoglobulin E (OVA‐IgE), transforming growth factor (TGF)‐β, tumor necrosis factor (TNF)‐α, adrenocorticotropic hormone (ACTH) and α‐melanocyte‐stimulating hormone (α‐MSH) between control and iNOS−/− mice. Eight‐week‐old control and iNOS−/− male C57BL/6j mice were sensitized three times with OVA antigen. Before and after the last skin sensitization, the number of scratching incidents and the... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5196558 Fri, 05 Aug 2011 23:00:00 +0100 5196558 http://www.medworm.com/index.php?rid=5097938&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01359.x AbstractHailey‐Hailey disease (HHD) is an autosomal dominant disorder characterized by suprabasal cutaneous cell separation (acantholysis) leading to the development of erosive and oozing skin lesion. Micro RNAs (miRNAs) are endogenous post‐transcriptional modulators of gene expression with critical functions in health and disease. Here, we evaluated whether the expression of specific miRNAs may play a role in the pathogenesis of HHD. Here, we report that miRNAs are expressed in a non‐random manner in Hailey‐Hailey patients. miR‐125b appeared a promising candidate for playing a role in HHD manifestation. Both Notch1 and p63 are part of a regulatory signaling whose function is essential for the control of keratinocyte proliferation and differentiation and of note, the expression o... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5097938 Fri, 05 Aug 2011 23:00:00 +0100 5097938 http://www.medworm.com/index.php?rid=5097937&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01360.x AbstractTo elucidate the possible involvement of nitric oxide (NO) derived from inducible NO‐synthase (iNOS) in the pathogenesis of patients with allergic rhinitis, we used an animal model of atopic dermatitis (AD) induced by epicutaneous sensitization and analyzed the differences in ear thickness, the frequency of scratching, and plasma levels of OVA‐specific immunoglobulin E (OVA‐IgE), transforming growth factor (TGF)‐β, tumor necrosis factor (TNF)‐α, adrenocorticotropic hormone (ACTH) and α‐melanocyte stimulating hormone (α‐MSH) between control and iNOS‐/‐ mice. Eight‐week‐old control and iNOS‐/‐ male C57BL/6j mice were sensitized three times with ovalbumin (OVA) antigen. Before and after the last skin sensitization, the number of scratching behaviors and t... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5097937 Sun, 31 Jul 2011 23:00:00 +0100 5097937 http://www.medworm.com/index.php?rid=5070306&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01358.x In this study, we characterized copy number changes of NAV3 in 24 basal cell cancers (BCCs), 8 squamous cell cancers (SCCs), and 8 non‐malignant inflammatory skin lesions by fluorescent in situ hybridization (FISH). To identify genes affected by NAV3, we used oligo siRNA gene silencing and gene microarrays to analyze gene expression profiles at several time points post transfection in primary human keratinocytes.We found NAV3 copy number loss and decreased protein expression in 21% of the BCCs and 25% of the SCCs. In the nodular/superficial BCC subgroup, low‐level NAV3 amplification was also observed. NAV3 aberrations were independent of the known chromosome 6 amplifications in BCC. Chromosome 12 polysomy was detected in 33% and 25% of the invasive type of BCC and SCC, respectively. Si... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5070306 Thu, 28 Jul 2011 01:48:38 +0100 5070306 http://www.medworm.com/index.php?rid=5225714&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01357.x Abstract:  Th2‐dominated immune responses are believed to contribute to the pathogenesis of atopic dermatitis (AD). IL‐4 and IL‐13 are typical pleiotropic Th2 cytokines that play a central role in IgE‐dependent inflammatory reactions. Single‐nucleotide polymorphisms (SNPs) in IL‐4 and IL‐13 have been reported in patients with allergic disease from numerous countries. Gene–gene interactions among genes have been identified in patients with asthma, although negative results have been reported. To investigate the associations of SNPs in these genes and the interactions between these genes in AD, we genotyped 23 SNPs of the IL‐4, IL‐13, IL‐4R, IL‐13Rα1 and IL‐13Rα2 genes for 1089 case‐control samples (631 AD patients and 458 controls) and analysed the SNPs and h... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5225714 Wed, 27 Jul 2011 04:00:00 +0100 5225714 http://www.medworm.com/index.php?rid=5070311&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01353.x AbstractWe investigated the effect of topical epigallocatechin‐3‐gallate (EGCG) on testosterone (T)‐induced hair loss in mice. Marked hair loss was observed at the T‐injected site and topical EGCG significantly reduced the hair loss (p < 0.05). TUNEL staining showed apoptosis of follicular epithelial cells in the T‐injected groups where topical EGCG was found to significantly diminish T‐induced apoptosis (p < 0.05). Topical EGCG down‐regulated the T‐induced expression of androgen receptor, but did not down‐regulate 17ß‐hydroxysteroid dehydrogenase (HSD) and 3ß‐HSD expression. Analysis using liquid chromatography tandem mass spectrometry (LC‐MS/MS) on serum and tissue samples revealed no significant difference in T and dihydrotestosterone (DHT) concentrations... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5070311 Tue, 26 Jul 2011 23:00:00 +0100 5070311 http://www.medworm.com/index.php?rid=5070310&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01354.x AbstractSkin is constantly exposed to physical and chemical stressors. The exposure of keratinocytes to ultraviolet B (UVB) irradiation causes epidermal damage via induction of apoptosis. Erythroid differentiation regulator 1 (Erdr1) modulates growth and survival of cells under various stressful conditions, but the function of Erdr1 in human keratinocyte apoptosis has not been investigated so far. Here, we investigated the effect of Erdr1 on UVB‐induced apoptosis in human keratinocytes and also examined the underlying regulatory mechanism. First, Erdr1 expression was detected in human primary keratinocytes and normal human skin tissues. Expression of Erdr1 was enhanced in human keratinocytes following UVB irradiation. Knock‐down of Erdr1 led to resistance to UVB‐induced apoptosis. Al... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5070310 Tue, 26 Jul 2011 23:00:00 +0100 5070310 http://www.medworm.com/index.php?rid=5070309&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01355.x AbstractA balanced proteolytic activity in the epidermis is vital to maintain epidermal homeostasis and barrier function. Distinct protease‐inhibitor systems are operating in different epidermal layers. In the uppermost layer, the stratum corneum, kallikrein‐like proteases and their inhibitors are responsible for desquamation of the cornified keratinocytes, thus regulating the integrity of the epidermal barrier. Following discovery and characterisation of the human multidomain inhibitor LEKTI (lympho‐epithelial Kazal‐type related inhibitor, encoded by hspink5), several new members of the Kazal‐type inhibitor family have been identified. Here we describe expression and regulation of murine SPINK12, a potential orthologue of human LEKTI2. Its expression was analysed by RT‐PCR and... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5070309 Tue, 26 Jul 2011 23:00:00 +0100 5070309 http://www.medworm.com/index.php?rid=5070308&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01356.x AbstractThree major difficulties must be overcome to establish a quantitative method for melanosomal transfer analysis: i) establishing a three‐dimensional co‐culture reassuring direct melanocyte to keratinocyte transfer, ii) separation of melanocytes and keratinocytes following co‐culture, and iii) melanosome quantification in each cell population. Melanocytes and keratinocytes are cultured on the opposite sides of the porous membrane of hanging cell inserts (1 μm pores, 2 106 pores/cm2). Cell separation is performed after 3 days of co‐culture by simple trypsinisation. Melanosome quantification in separated cell populations was accomplished by an ELISA‐like method using gp‐100 as the antigen. Melanocytes and keratinocytes come into “direct” contact through the pores and m... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5070308 Tue, 26 Jul 2011 23:00:00 +0100 5070308 http://www.medworm.com/index.php?rid=5070307&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01357.x AbstractTh2‐dominated immune responses are believed to contribute to the pathogenesis of atopic dermatitis (AD). IL‐4 and IL‐13 are typical pleiotropic Th2 cytokines that play a central role in IgE‐dependent inflammatory reactions. Single nucleotide polymorphisms (SNPs) in IL‐4 and IL‐13 have been reported in allergic disease patients from numerous countries. Gene‐gene interactions among genes have been identified in asthma patients, although negative results have been reported.To investigate the associations of SNPs in these genes and the interactions between these genes in AD, we genotyped 23 SNPs of the IL‐4, IL‐13, IL‐4R, IL‐13Rα1, and IL‐13Rα2 genes for 1,089 case‐control samples (631 AD patients and 458 controls) and analysed the SNPs and haplotypes in the... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5070307 Tue, 26 Jul 2011 23:00:00 +0100 5070307 http://www.medworm.com/index.php?rid=5039801&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01351.x AbstractNumerous wrinkles are observed in the skin of streptozotocin (STZ)‐induced type 1 diabetic rats, which are similar to those seen in vitamin A‐deficient (VAD) rats. Retinoic acid (RA), the active form of vitamin A, promotes the production of collagen in dermis and induces cell growth and inhibition of epidermal differentiation in skin tissues. Normal skin function is maintained by the extracellular matrix (ECM)‐degrading enzymes, matrix metalloproteinase (MMP) and hyaluronidase (HAase). The current study is the first comparison of MMP and HAase activities in skin tissues of type 1 diabetic, VAD and RA‐treated animal models. In skin tissues of type 1 diabetic and VAD rats or VAD mice, both MMP‐2 and HAase activities increased as compared with controls. In contrast, MMP and ... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5039801 Wed, 20 Jul 2011 16:25:19 +0100 5039801 http://www.medworm.com/index.php?rid=5161864&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01351.x This study is the first comparison of MMP and HAase activities in skin tissues of type 1 diabetic, VAD and RA‐treated animal models. In skin tissues of type 1 diabetic and VAD rats or VAD mice, both MMP‐2 and HAase activities increased as compared with controls. In contrast, MMP and HAase activities were reduced in the skin tissues of RA‐treated mice. Blood retinol levels in type 1 diabetic rats were lower than controls. These results indicate a close relationship between type 1 diabetes and vitamin A‐deficiency on MMP and HAase in skin tissues, suggesting that type 1 diabetic rats could be vitamin A‐deficient. Vitamin A‐derived RA might be a significant regulator of ECM‐degrading enzyme expression and diabetic symptoms. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5161864 Mon, 18 Jul 2011 23:00:00 +0100 5161864 http://www.medworm.com/index.php?rid=5039802&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01350.x AbstractUVA‐induced gene expression is supposed to be a hallmark for inflammation, immunosuppression and in long‐terms cancer formation. In previous studies, we have shown for keratinocytes that physiological doses of UVA radiation result in upregulation of gene expression mediated by ceramide formation from sphingolipids/cholesterol rich microdomains (rafts) which can be blocked by preloading keratinocytes with cholesterol or plant sterols. Here, we show that besides stigmasterol and ß‐sitosterol also sterols like 14‐dehydroergosterol, ergosterol‐peroxide and 29‐norcycloartenol inhibit the UVA response. Moreover, we present evidence that natural material derived triterpenoids such as oleanolic acid can abrogate UVA induced gene expression by raft stabilization. This effect de... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5039802 Mon, 18 Jul 2011 23:00:00 +0100 5039802 http://www.medworm.com/index.php?rid=5030494&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01347.x Abstract:Epidermal basement membrane forms anchoring complex composed of hemidesmosomes, anchoring filaments, lamina densa and anchoring fibrils to link epidermis to dermis. However, the anchoring complex is rarely formed in skin equivalent models, probably due to degradation of extracellular matrix (ECM) proteins and heparan sulfate chains by matrix metalloproteinases (MMPs) and heparanase, respectively. To explore the roles of ECM proteins and heparan sulfate in anchoring complex assembly, we used specific inhibitors of MMPs and heparanase, and the formation of anchoring complex was analyzed in terms of polarized deposition of collagen VII, BP180 and β4 integrin at the dermal‐epidermal junction (DEJ) by means of immunohistochemistry and transmission electron microscopy (TEM). The depo... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5030494 Sat, 16 Jul 2011 16:17:43 +0100 5030494 http://www.medworm.com/index.php?rid=5020880&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01331.x (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5020880 Wed, 13 Jul 2011 16:37:14 +0100 5020880 http://www.medworm.com/index.php?rid=5020873&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01346.x Abstract:To elucidate the mechanisms of severe itch in atopic dermatitis, we investigated the role of leukotriene B4, a potent itch mediator, in spontaneous itch‐related behavior in NC mice with atopic dermatitis‐like skin lesions. Topical application of the BLT leukotriene B4 receptor antagonist ONO‐4057 inhibited spontaneous itch‐related behavior. The concentration of leukotriene B4 was significantly increased in the lesional skin. The expression levels of 5‐lipoxygenase were also elevated in the lesional skin, yet present throughout the epidermis of both healthy and lesional skin. These results suggest a role for leukotriene B4 in chronic dermatitis‐related itch. Sphingosylphosphorylcholine was increased in the epidermis of the lesional skin. Moreover, intradermal injection ... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5020873 Wed, 13 Jul 2011 16:36:36 +0100 5020873 http://www.medworm.com/index.php?rid=5109552&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01347.x Abstract:  Epidermal basement membrane forms anchoring complex composed of hemidesmosomes, anchoring filaments, lamina densa and anchoring fibrils to link epidermis to dermis. However, the anchoring complex is rarely formed in skin equivalent models, probably because of degradation of extracellular matrix (ECM) proteins and heparan sulfate chains by matrix metalloproteinases (MMPs) and heparanase, respectively. To explore the roles of ECM proteins and heparan sulfate in anchoring complex assembly, we used specific inhibitors of MMPs and heparanase, and the formation of anchoring complex was analysed in terms of polarized deposition of collagen VII, BP180 and β4 integrin at the dermal–epidermal junction (DEJ) by means of immunohistochemistry and transmission electron microscopy (TEM). ... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5109552 Tue, 12 Jul 2011 23:00:00 +0100 5109552 http://www.medworm.com/index.php?rid=5132228&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01345.x Abstract:  We synthesized a novel derivative of a well‐known skin‐lightening compound niacinamide, N‐nicotinoyl dopamine (NND). NND did not show inhibitory effects of tyrosinase and melanin synthesis in B16F10 mouse melanoma cells. However, NND retains high antioxidant activity without affecting viability of cells. In a reconstructed skin model, topical applications of 0.05% and 0.1% NND induced skin lightening and decreased melanin production without affecting the viability and morphology of melanocytes and overall tissue histology. Moreover, no evidence for skin irritation or sensitization was observed when 0.1% NND emulsion was applied onto the skin of 52 volunteers. The effect of NND on skin lightening was further revealed by pigmented spot analyses of human clinical trial. Ove... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5132228 Mon, 11 Jul 2011 23:00:00 +0100 5132228 http://www.medworm.com/index.php?rid=5109551&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01346.x Abstract:  To elucidate the mechanisms of severe itch in atopic dermatitis, we investigated the role of leukotriene B4, a potent itch mediator, in spontaneous itch‐related behaviour in NC mice with atopic dermatitis‐like skin lesions. Topical application of the BLT leukotriene B4 receptor antagonist ONO‐4057 inhibited spontaneous itch‐related behaviour. The concentration of leukotriene B4 was significantly increased in the lesional skin. The expression levels of 5‐lipoxygenase were also elevated in the lesional skin, yet present throughout the epidermis of both healthy and lesional skin. These results suggest a role for leukotriene B4 in chronic dermatitis‐related itch. Sphingosylphosphorylcholine (SPC) was increased in the epidermis of the lesional skin. Moreover, intraderma... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5109551 Mon, 11 Jul 2011 23:00:00 +0100 5109551 http://www.medworm.com/index.php?rid=5020878&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01341.x In this study, we analyzed statistically skin atrophy experiments retrospectively to ascertain 1.) the earliest time point, at which skin atrophy is significantly induced, and 2.) whether the differences between the GC treatment groups change until the end of the experiment. We show here that the treatment duration of rat skin atrophy models might be reduced to 5 days for economical and ethical reasons. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5020878 Mon, 11 Jul 2011 23:00:00 +0100 5020878 http://www.medworm.com/index.php?rid=5020877&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01342.x AbstractUltraviolet radiation (UVR) effects on skin have been extensively studied. However, mitochondrial dysfunction and superoxide (O2•‐) production have only been studied using cell cultures, which are useful models, but do not consider the crosstalk between tissues or cellular differentiation.We aimed to evaluate the usefulness of fluorescent dyes to study skin ex vivo. Mitochondrial alterations were evaluated in epidermal cells isolated from UVR‐exposed mice. Furthermore, a combination of dyes and antibodies was tested to analyze specific skin cell types.UVR caused a decrease in the percentage of total cells with polarized mitochondria, but did not change the mitochondrial O2•‐ production. However, this production was increased significantly in DiOC6+ cells. Furthermore, it ... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5020877 Mon, 11 Jul 2011 23:00:00 +0100 5020877 http://www.medworm.com/index.php?rid=5020876&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01343.x In this study, we explored an inhibitory effect of statins on CCL20/CCR6 interaction. We demonstrated that IL‐1β, TNF‐α, and IL‐17A significantly increased CCL20 production from HaCaT cells. However, these increments were markedly inhibited by fluvastatin and simvastatin, but not by pravastatin. In the chemotaxis migration assay, pretreatment with fluvastatin and simvastatin inhibited the migration of human CD4+ T cells toward CCL20. However, the level of CCR6 surface expression in memory CD4+ T cells was not affected. Our results suggest that not all, but specific types of statins may be of benefit in alleviating psoriasis partially via interrupting CCL20/CCR6 chemotactic interaction, the mechanism which may eventually lessen the infiltration of Th17 cells. (Source: Experimental D... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5020876 Mon, 11 Jul 2011 23:00:00 +0100 5020876 http://www.medworm.com/index.php?rid=5020875&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01344.x AbstractHidradenitis suppurativa is a chronically relapsing skin disorder with onset after puberty and is characterized by inflammatory lesions in hair follicle and apocrine sweat gland bearing skin that manifests as abscesses with formation of cysts and sinus tracts.Hedgehog family genes are required in normal embryonic skin, hair follicle, sebaceous and sweat gland development. Mutations of hedgehog pathway in adult skin have previously been found in basal cell carcinomas and in alopecia as well as in epidermal cysts and in odontogenic keratocysts. Therefore we suggested that the hedgehog pathway might play a role in formation of sinus tracts and cysts as newly formed structures in hidradenitis suppurativa patients.None of the sinus tracts or cysts in 81 hidradenitis suppurativa histolog... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5020875 Mon, 11 Jul 2011 23:00:00 +0100 5020875 http://www.medworm.com/index.php?rid=5020874&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01345.x Abstract:We synthesized a novel derivative of a well known skin lightening compound niacinamide, N‐Nicotinoyl dopamine (NND). NND did not show inhibitory effects of tyrosinase and melanin synthesis in B16F10 mouse melanoma cells. However, NND retains high anti‐oxidant activity without affecting viability of cells. In a reconstructed skin model, topical applications of 0.05 and 0.1% NND induced skin lightening and decreased melanin production without affecting the viability and morphology of melanocytes and overall tissue histology. Moreover, no evidence for skin irritation or sensitization was observed when 0.1% NND emulsion was applied onto the skin of 52 volunteers. The effect of NND on skin lightening was further revealed by pigmented spot analyses of human clinical trial. Overall, ... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5020874 Mon, 11 Jul 2011 23:00:00 +0100 5020874 http://www.medworm.com/index.php?rid=5020879&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01326.x Conclusions:  Our findings indicate that EcN alters the local allergen‐induced immune response by increase of Foxp3+ cells and by favouring an immunoregulatory cytokine pattern. Thus, oral administration of EcN might be an effective strategy in prevention and potentially therapy of allergic inflammatory skin diseases. (Source: Experimental Dermatology) Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5020879 Sun, 10 Jul 2011 23:00:00 +0100 5020879 http://www.medworm.com/index.php?rid=5009987&cid=s_31739_12_f&fid=31739&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1600-0625.2011.01327.x Abstract:  The human cathelicidin antimicrobial peptide LL‐37 regulates apoptosis of several cell types. Defective apoptosis of skin fibroblasts may contribute to systemic sclerosis (SSc). Here, we show that LL‐37 inhibited apoptosis of SSc fibroblasts and identified the signalling pathways by which LL‐37 mediates apoptosis. Immunohistochemistry showed that cathelicidin expression was enhanced in SSc patients compared with healthy controls. In addition, LL‐37 decreased sodium nitroprusside (SNP)‐induced apoptosis of SSc fibroblasts. LL‐37 significantly increased expression of Bcl‐2 and decreased levels of BAX protein. Pretreatment with LL‐37 decreased activation of caspase‐3 following SNP‐treatment. Moreover, exposure of SSc fibroblasts to LL‐37 resulted in increase... Experimental Dermatology journals http://www.medworm.com/rss/comments.php?id=5009987 Wed, 06 Jul 2011 23:00:00 +0100 5009987