Showing papers in "Archives of Dermatological Research in 2010"
TL;DR: It is suggested that polyphenols may favorably supplement sunscreens protection, and may be useful for skin diseases associated with solar UV radiation-induced inflammation, oxidative stress and DNA damage.
Abstract: Epidemiological, clinical and laboratory studies have implicated solar ultraviolet (UV) radiation in various skin diseases including, premature aging of the skin and melanoma and non-melanoma skin cancers. Chronic UV radiation exposure-induced skin diseases or skin disorders are caused by the excessive induction of inflammation, oxidative stress and DNA damage, etc. The use of chemopreventive agents, such as plant polyphenols, to inhibit these events in UV-exposed skin is gaining attention. Chemoprevention refers to the use of agents that can inhibit, reverse or retard the process of these harmful events in the UV-exposed skin. A wide variety of polyphenols or phytochemicals, most of which are dietary supplements, have been reported to possess substantial skin photoprotective effects. This review article summarizes the photoprotective effects of some selected polyphenols, such as green tea polyphenols, grape seed proanthocyanidins, resveratrol, silymarin and genistein, on UV-induced skin inflammation, oxidative stress and DNA damage, etc., with a focus on mechanisms underlying the photoprotective effects of these polyphenols. The laboratory studies conducted in animal models suggest that these polyphenols have the ability to protect the skin from the adverse effects of UV radiation, including the risk of skin cancers. It is suggested that polyphenols may favorably supplement sunscreens protection, and may be useful for skin diseases associated with solar UV radiation-induced inflammation, oxidative stress and DNA damage.
844 citations
TL;DR: A varied inheritance pattern in KD is indicated (predominantly autosomal dominant), linkage loci (chromosomes 2q23 and 7p11), several human leukocyte antigen alleles (HLA-DRB1*15, HLA-DQA1*0104), negative candidate gene case–control association studies and at least 25 dysregulated genes reported in multiple microarray studies.
Abstract: Keloid scarring, also known as keloid disease (KD), is a common, abnormally raised fibroproliferative cutaneous lesion that can occur following even minor skin trauma. The aetiopathogenesis of KD has remained an enigma todate compounded by an ill-defined clinical management. There is strong evidence suggesting a genetic susceptibility in individuals affected by KD, including familial heritability, common occurrence in twins and high prevalence in certain ethnic populations. This review aims to address the genetic aspects of KD that have been described in present literature that include inheritance patterns, linkage studies, case-control association studies, whole genome gene expression microarray studies and gene pathways that were significant in KD. In addition to our clinical and scientific background in KD, we used search engines, Scopus, Scirus and PubMed, which searched for key terms covering various genetic aspects of KD. Additionally, genes reported in seven whole genome gene expression microarray studies were separately compared in detail. Our findings indicate a varied inheritance pattern in KD (predominantly autosomal dominant), linkage loci (chromosomes 2q23 and 7p11), several human leukocyte antigen (HLA) alleles (HLA-DRB1*15, HLA-DQA1*0104, DQ-B1*0501 and DQB1*0503), negative candidate gene case-control association studies and at least 25 dysregulated genes reported in multiple microarray studies. The major pathways reportedly proposed to be involved in KD include apoptosis, mitogen-activated protein kinase, transforming growth factor-beta, interleukin-6 and plasminogen activator inhibitor-1. In summary, involvement of more than one gene is likely to be responsible for susceptibility to KD. A better understanding of the genes involved in KD may potentially lead to the development of more effective diagnostic, therapeutic and prognostic measures.
224 citations
TL;DR: UV radiation is known to activate multiple signalling cascades such as the p38 MAPK, Jun N-terminal kinase, extracellular signal-regulated kinase 1/2 and NFκB pathways in skin cells, which plays a role in mediating the release of cytokines such as TNFα.
Abstract: The sun emits different types of ultraviolet (UV) light. Our skin is a natural target of UV radiation which is involved in vitamin D3 production in our body. UV radiation at high doses is an environmental carcinogen which can elicit skin damage as well as inducing skin cancer. It can mediate inflammatory and immunological reactions through activation of receptors, DNA/RNA damage and production of reactive oxygen species. It is also involved in the release of pro-inflammatory cytokines, of which TNFalpha has been implicated in tumorigenic activities. In order to mediate its effects, UV radiation is known to activate multiple signalling cascades such as the p38 MAPK, Jun N-terminal kinase, extracellular signal-regulated kinase 1/2 and NFkappaB pathways in skin cells. The role each of these pathways plays in mediating the release of cytokines such as TNFalpha remains to be fully characterized. Once the function of these pathways is known, this information may provide for the formulation of therapy which will prevent the release of immunosuppressive cytokines resulting in a reduction in skin cancer formation.
216 citations
TL;DR: Most of the differences between fetal and adult skin were found at the level of dermal extracellular matrix molecules expression, suggesting that dermal components are important in fetal scarless healing.
Abstract: Healing of early-gestation fetal wounds results in scarless healing. Since the capacity for regeneration is probably inherent to the fetal skin itself, knowledge of the fetal skin composition may contribute to the understanding of fetal wound healing. The aim of this study was to analyze the expression profiles of different epidermal and dermal components in the human fetal and adult skin. In the human fetal skin (ranging from 13 to 22 weeks' gestation) and adult skin biopsies, the expression patterns of several epidermal proteins (K10, K14, K16, K17, SKALP, involucrin), basement membrane proteins, Ki-67, blood vessels and extracellular matrix proteins (fibronectin, chondroitin sulfate, elastin) were determined using immunohistochemistry. The expression profiles of K17, involucrin, dermal Ki-67, fibronectin and chondroitin sulfate were higher in the fetal skin than in adult skin. In the fetal skin, elastin was not present in the dermis, but it was found in the adult skin. The expression patterns of basement membrane proteins, blood vessels, K10, K14, K16 and epidermal Ki-67 were similar in human fetal skin and adult skin. In this systematic overview, most of the differences between fetal and adult skin were found at the level of dermal extracellular matrix molecules expression. This study suggests that, especially, dermal components are important in fetal scarless healing.
124 citations
TL;DR: Results indicate that PAR-2 plays an important role in the pathogenesis of acne by inducing inflammatory mediators in response to proteases secreted from P. acnes.
Abstract: Propionibacterium acnes (P. acnes) has been known to produce various exogenous proteases, however, their role in acne pathogenesis remains largely unknown. Proteases elicit cellular responses, at least in part, via proteinase-activated receptor-2 (PAR-2), which is known to mediate inflammation and immune response. In this study, we investigated whether proteases from P. acnes could activate PAR-2 on keratinocytes and induce pro-inflammatory cytokines, antimicrobial peptides (AMPs), and matrix metalloproteinases (MMPs) via PAR-2 signaling. We examined PAR-2 expression and protease activity in acne lesions using immunofluorescence staining and in situ zymography. The effect of the culture supernatant of P. acnes on Ca2+ signaling in immortalized keratinocytes (HaCaT) was measured using a fluorescence method. HaCaT cells were treated with P. acnes strain ATCC 6919 culture supernatant, with or without pretreatment with serine protease inhibitor or selective PAR-2 antagonist and the gene expression of pro-inflammatory cytokines, AMPs, and MMPs was detected using real-time reverse transcription-polymerase chain reaction. We found that the protease activity and PAR-2 expression were increased in acne lesions. The P. acnes culture supernatant induced calcium signaling in keratinocytes via PAR-2 and stimulated the mRNA expression of interleukin (IL)-1α, -8, tumor necrosis factor (TNF)-α, human beta defensin (hBD)-2, LL-37, MMP-1, -2, -3, -9, and -13 in keratinocytes, which was significantly inhibited by serine protease inhibitor as well as selective PAR-2 specific antagonist. These results indicate that PAR-2 plays an important role in the pathogenesis of acne by inducing inflammatory mediators in response to proteases secreted from P. acnes.
106 citations
TL;DR: Levels of proteases such as PMN elastase, matrix metalloproteinases-2, and MMP-2 were found to be profoundly elevated in chronic when compared with acute wound fluids, and concentrations of IL-1β, IL-6, and IL-8 were shown to be significantly higher in chronic than in acute wounds.
Abstract: Physiological wound repair is a highly regulated, complex process, which leads to formation of new tissue after injury. However, the healing process is not perfect and healing impairments can occur. Delayed healing and formation of chronic wounds has been linked to the excessive production of proteolytic enzymes leading to reduced amounts of growth factors and successive destruction of the extracellular matrix. It has been implied that there is an alteration in the normal control mechanisms regulating the levels of these enzymes. The study presented provides data on the concentration of proteases and cytokines in wound fluid from chronic when compared with acute wounds. Levels of proteases such as PMN elastase, matrix metalloproteinases-2 (MMP-2), and MMP-13 were found to be profoundly elevated in chronic when compared with acute wound fluids. In addition, concentrations of IL-1β, IL-6, and IL-8 were shown to be significantly higher in chronic than in acute wounds. Furthermore, the ability of a wound dressing, consisting of bovine collagen type I, to bind pro-inflammatory cytokines was investigated. Collagen type I was able to bind significant amounts of the pro-inflammatory cytokines in vitro. Thus, it should be able to establish a more physiological wound milieu in vivo and promote healing.
98 citations
TL;DR: Taken together, both PVE and RA prevent UVB-caused injury to keratinocytes, however their efficacy needs to be demonstrated in vivo.
Abstract: Solar radiation is a very important exogenous factor in skin pathogenesis and can lead to the development of a number of skin disorders. UVB irradiation is known to induce oxidative stress, inflammation and especially DNA lesions in exposed cells. It is important, therefore, to identify agents that can offer protection against UVB-caused skin damage. Natural compounds have been studied for their possible ability to control/modulate various lifestyle-related diseases. The application of plant compounds/extracts with screening, antioxidant and anti-inflammatory activities may also successfully protect the skin against UV-caused injury. We assessed the potency of Prunella vulgaris extract (PVE) and its main phenolic acid component, rosmarinic acid (RA), to suppress UVB-induced (295-315 nm) alterations to human keratinocytes HaCaT using a solar simulator. Pre- and post-treatment of HaCaT cells with PVE (5-50 mg/l) and RA (0.18-1.8 mg/l) reduced breakage together with the apoptotic process. PVE and RA also significantly eliminated ROS production and diminished IL-6 release. Taken together, both PVE and RA prevent UVB-caused injury to keratinocytes. However their efficacy needs to be demonstrated in vivo.
93 citations
TL;DR: The results indicate that IL-17F produced by CD4+ T cells causes the inflammation in psoriasis partly through induction of IL-6 in keratinocytes.
Abstract: Recently, the important role of T helper 17 (Th17) cells in psoriasis has been clarified; however, the role of IL-17F produced by Th17 cells is still not fully understood. IL-6 exhibits multiple biologic functions, such as regulation of immunological responses including those in psoriatic reactions. Therefore, we examined the production of IL-6 protein in normal human epidermal keratinocytes (NHEKs) stimulated by IL-17F, TNF-α, IL-17A, and IL-17A in combination with TNF-α, and PBS control. We then examined the expression of IL-6 mRNA in mouse skin after intradermal injection of IL-17F. Finally, IL-17F expression in skin biopsy specimens from psoriasis patients was examined by immunohistochemistry. The results showed that IL-17F induced production of IL-6 in NHEKs in a time-dependent manner. This could be attenuated by chimeric inhibitor blocking the IL-17 receptor. The amounts of IL-6 stimulated by IL-17F were much higher than those stimulated by TNF-α or IL-17A. IL-6 was also significantly upregulated via synergistic stimulation with IL-17A plus TNF-α. The expression of IL-6 mRNA 24 h after IL-17F injection in the mouse skin was 3.2-fold higher than that in the control group. Immunohistochemistry of inflammatory cells in the dermis demonstrated a large number of CD4+ T cells showing IL-17F positivity in psoriatic skin lesions, but few or none in non-lesional psoriatic skin. Our results indicate that IL-17F produced by CD4+ T cells causes the inflammation in psoriasis partly through induction of IL-6 in keratinocytes.
86 citations
TL;DR: UVB-induced ROS formation, cell fatality, lipid peroxidation, antioxidant depletion and oxidative DNA damage in HDFa cells is inhibited by sesamol, which, probably through its ROS scavenging activity, shows maximum protection for UVB- induced oxidative damage.
Abstract: The exposure of cells to ultraviolet B radiation (UVB) can induce the production of reactive oxygen species (ROS) which damage cellular components. Free radical scavengers and antioxidants can interfere with the production of ROS. We studied cytotoxicity, intracellular ROS levels, lipid peroxidation, antioxidant status and oxidative DNA damage in cultured human skin dermal fibroblast adult cells (HDFa) exposed to UVB in the presence of sesamol, a natural phenolic compound. The levels of cytotoxicity, intracellular ROS, lipid peroxidation, oxidative DNA damage and apoptotic morphological changes were significantly increased in UVB irradiated HDFa cells. We also observed that the activities of enzymatic antioxidants (superoxide dismutase, catalase and glutathione peroxidase) and the levels of non-enzymatic antioxidant status (GSH) were significantly decreased in UVB irradiated cells. On the other hand, sesamol pretreatment significantly decreased cytotoxicity, intracellular ROS, lipid peroxidation, oxidative DNA damage and apoptotic morphological changes in sesamol-pretreated and UVB-irradiated HDFa cells. We have also observed increased enzymatic and non-enzymatic antioxidants status in sesamol plus UVB-irradiated cells. Among the different doses tested, 80 μM of sesamol shows maximum protection for UVB-induced oxidative damage. In conclusion, UVB-induced ROS formation, cell fatality, lipid peroxidation, antioxidant depletion and oxidative DNA damage in HDFa cells is inhibited by sesamol, which, probably through its ROS scavenging activity.
83 citations
TL;DR: Clinical effects and adverse events of IA in more than 50 reported patients with autoimmune blistering disorders are reviewed and an overview of the available IA systems and treatment protocols is provided and guidelines of a recent consensus of German, Austrian, and Swiss experts are summarized.
Abstract: Immunoadsorption (IA), also termed immunoapheresis, has been established as effective and specific tool advantageous to plasmapheresis to remove immunoglobulin and immune complexes and in cytapheresis, immune cells from the circulation. IA was successfully used in various autoantibody-mediated diseases, e.g. acquired hemophilia, myasthenia gravis, dilated cardiomyopathy, and Guillain-Barre syndrome. In dermatology, IA has been applied as an effective adjuvant treatment for autoimmune bullous diseases. Autoimmune blistering disorders are a heterogeneous group of diseases that are associated with autoantibodies to desmosomal (pemphigus group) and basal membrane zone proteins (pemphigoid group, epidermolysis bullosa acquisita). Because the pathogenic relevance of autoantibodies was clearly demonstrated in the majority of these disorders, removal of autoantibodies, therefore, appears to be a rational therapeutic approach for these patients. IA has been shown to effectively lower the autoantibody levels and leads to rapid clinical responses in patients with immunobullous disorders. Here, clinical effects and adverse events of IA in more than 50 reported patients with autoimmune blistering disorders are reviewed. In addition, an overview of the available IA systems and treatment protocols is provided and guidelines of a recent consensus of German, Austrian, and Swiss experts for the use of IA in autoimmune bullous diseases are summarized.
82 citations
TL;DR: The data of this study provide evidence that DMF is most likely absorbed out of the duodenum into the presystemic circulation and is not completely hydrolysed to MMF before uptake as assumed by others.
Abstract: The aim of this study was to evaluate pharmacokinetic parameters of fumaric acid esters (FAE) in psoriasis patients for the first time. For this prupose new HPLC assays were developed. Additionally, physicochemical parameters of FAE were determined, allowing a better interpretation of the in vivo data. In vivo, monomethylfumarate (MMF) and monoethylfumarate (MEF) were detected after tlag = 120 min. Tmax and cmax of MMF were 210 min and 11.2 μM, respectively, 210 min and 5.2 μM for MEF. The half-life of MMF was 38.7 min, and 25.4 min of MEF. The AUC0–∞ of MMF was 172 min μg ml−1 and 63.6 min μg ml−1 of MEF. Data display median of three subjects. No plasma levels of dimethylfumarate (DMF) or fumaric acid (FA) were detected. The evaluation of physicochemical parameters of FAE showed that only DMF fulfils the criteria of Lipinski’s rule of five. The pKa of MMF was determined as 3.63. The data of this study provide evidence that DMF is most likely absorbed out of the duodenum into the presystemic circulation and is not completely hydrolysed to MMF before uptake as assumed by others.
TL;DR: It is proposed that a new way of considering the pathergy reaction is to see it as an aberration of the skin’s innate reactivity from a homeostatic reactive mode closely coupled to tissue healing to an abnormal destructive/inflammatory mode.
Abstract: Pathergy is the term used to describe hyper-reactivity of the skin that occurs in response to minimal trauma. A positive skin pathergy test (SPT), characterised by erythematous induration at the site of the needle stick with a small pustule containing sterile pus at its centre, is among the criteria required for a diagnosis of Behcet's disease (BD) and in certain population has been shown to be highly specific for this condition. Problems with standardising the induction manoeuvre for the SPT as well as the method of assessment of the response have limited the usefulness of the SPT in the clinical setting. Extensive investigation into histopathological and immunological aspects of pathergy has led to a number of hypotheses relating to the aetiology of the skin pathergy reaction and the disease itself, but the cause is considered to be unknown. Pathergy lesions, the development of new skin lesions or the aggravation of existing ones following trivial trauma, are also reported in pyoderma gangrenosum and has been noted in other neutrophilic dermatoses such as Sweet's syndrome. The response of such patient groups to the systematic application of the SPT has not been described. We propose that a new way of considering the pathergy reaction is to see it as an aberration of the skin's innate reactivity from a homeostatic reactive mode closely coupled to tissue healing to an abnormal destructive/inflammatory mode. Our understanding of BD and other similar conditions would profit by more detailed mechanistic knowledge of skin homeostasis to minimal trauma in both health and disease through a more structured and systematic use of the SPT.
TL;DR: Immunohistological studies and cell culture experiments indicate that dysbalances in elastin turnover are associated with pathological degradative processes including increased elastolytic activity that finally lead to loss of elastic fibres in the mid-dermis.
Abstract: The clinical as well as histological data of 79 mid-dermal elastolysis (MDE) patients reported in the literature were evaluated. MDE is an acquired skin condition of the elastic tissue predominantly manifesting on the trunk and proximal extremities of young women. Most commonly observed skin changes include patches of well-circumscribed fine wrinkles (type I) and perifollicular papular protrusions (type II). Rarely, MDE may also occur with persistent reticular erythema and wrinkling (type III). The critical diagnostic histopathological feature of MDE is the selective loss of elastic fibres in the mid-dermis. Mild lymphohistiocytic infiltrates, elastophagocytosis of elastic fibres by macrophages, and even multinucleate giant cells are occasionally observed in MDE lesions. Immunohistological studies and cell culture experiments indicate that dysbalances in elastin turnover are associated with pathological degradative processes including increased elastolytic activity that finally lead to loss of elastic fibres in the mid-dermis. First-line differential diagnoses may include closely related conditions such as anetoderma, annular elastolytic giant cell granuloma, cutis laxa acquisita and pseudoxanthoma elasticum-like papillary dermal elastolysis. Future therapeutic approaches in MDE patients should focus on agents that are able to block increased elastase activity and induce elastin synthesis.
TL;DR: The GABA ligand and its GABAA R may play a role for the pathogenesis of psoriasis as well as for pruritus in this disease.
Abstract: Psoriasis is a chronic inflammatory disease in which pruritus is a common symptom. Pruritus may be associated with the gamma-aminobutyric acid (GABA) system. The distribution of GABA and its GABAA receptor (R) was studied in involved and non-involved psoriatic skin, as well as normal healthy control skin, using an immunohistochemistry technique. Pruritus was determined using a visual analog scale. Inflammatory cells immunoreactive for the GABA ligand and the GABAA R were increased (P < 0.01, respectively) in the involved skin. Cells stained for GABA ligand were mostly macrophages with some lymphocytes, while cells stained for GABAA R were macrophages, neutrophils or lymphocytes. There was a positive correlation when comparing GABA ligand (P = 0.05) and GABAA R (P < 0.05) expressing inflammatory cells, with pruritus. The GABA ligand and its GABAA R may play a role for the pathogenesis of psoriasis as well as for pruritus in this disease.
TL;DR: The results have led to the conclusion that the excessive production of ECM in the KF cells could be blocked and/or rapidly decreased by curcumin.
Abstract: Keloid is a fibrotic disease characterized by abnormal accumulation of extracellular matrix (ECM) in the dermis It is a late spreading skin overgrowth and may be considered a plastic surgeon’s nightmare In nature, curcuminoid is composed of curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (bDMC) Curcuminoids have been found to inhibit fibrosis However, their role in the synthesis of ECM in the keloid fibroblasts (KFs) has remained unclear In this series of studies, a total of seven primary KFs cultures were used as the KFs model for investigating the inhibitory effect of curcuminoids on the expression of ECM and TGF-β1 A sensitive and reproducible HPLC method was developed to provide a quantitative analysis on the cellular uptake of curcuminoids onto the KF cells The level of ECM in the primary KFs was elevated The elevation of ECM and TGF-β1/p-SMAD-2 level was substantially blocked by the cellular uptake of curcumin in a dose-dependent manner in all the seven primary KFs The results have led to the conclusion that the excessive production of ECM in the KF cells could be blocked and/or rapidly decreased by curcumin
TL;DR: A potential role for FAP-α and DPPIV in the invasive behavior of keloids is suggested, rather than by modulating inflammation or ECM production, which is considered to be a novel treatment option to prevent keloid progression.
Abstract: Keloid scars are common benign fibroproliferative reticular dermal lesions with unknown etiology and ill-defined management with high rate of recurrence post surgery. The progression of keloids is characterized by increased deposition of extracellular matrix proteins, invasion into the surrounding healthy skin and inflammation. Fibroblasts are considered to be the key cellular mediators of fibrogenesis in keloid scars. Fibroblast activation protein alpha (FAP-α) and dipeptidyl peptidase IV (DPPIV) are proteases located at the plasma membrane promoting cell invasiveness and tumor growth and have been previously associated with keloid scars. Therefore, in this study we analyzed in further detail the expression of FAP-α in keloid fibroblasts compared to control skin fibroblasts. Dermal fibroblasts were obtained from punch-biopsies from the active margin of four keloids and four control skin samples. Flow cytometry was used to analyze FAP-α expression and the CytoSelect® 24-Well Collagen I Cell Invasion Assay was applied to study fibroblast invasion. Secretion of extracellular matrix (ECM) proteins was investigated by multiplexed particle-based flow cytometric assay and enzyme-linked immunosorbent assay. We found an increased expression of FAP-α in keloid fibroblasts compared to control skin fibroblasts (p < 0.001). Inhibition of FAP-α/DPPIV activity using the irreversible inhibitor H2N-Gly-Pro diphenylphosphonate reduced the increased invasiveness of keloid fibroblasts (p < 0.001) indicating that keloid invasion may be partly FAP-α/DPPIV mediated. FAP-α/DPPIV inhibition had no effect, (a) on the synthesis of the ECM proteins procollagen type I C-terminal peptide and fibronectin, (b) on the production of fibroblast growth factor or vascular endothelial growth factor, (c) on the expression of the proinflammatory cytokines interleukin-6 (IL-6), interleukin 8 (IL-8) or monocyte chemotactic protein-1. These results suggest a potential role for FAP-α and DPPIV in the invasive behavior of keloids. FAP-α and DPPIV may increase the invasive capacity of keloid fibroblasts rather than by modulating inflammation or ECM production. Since FAP-α expression is restricted to reactive fibroblasts in wound healing and normal adult tissues are generally FAP-α negative, inhibiting FAP-α/DPPIV activity may be a novel treatment option to prevent keloid progression.
TL;DR: The addition of tamoxifen, a non-steroidal anti-estrogen, usually used in breast cancer, to standard treatment may lead to improved wound healing in keloids by decreasing the expression of TGF-β1, with the consequent inhibitions of both fibroblast proliferation and collagen production.
Abstract: As acute burn patients have experienced increasing survival rates, the number of patients who need specific care due to aberrant scarring is also increasing. The burned skin often responds with fibrotic tissue proliferation, which can lead to a hypertrophic scar or a keloid. Non-physiologic scars are mostly not acceptable for the burn patient. Intradermal and topical therapy in burns comprise the treatment of the skin injury and its possible texture, elasticity and color alterations with the aid of active substances that result in fibroblastic modulation. An alteration of cytokine levels may mediate these effects, and evidences suggest that keloid scar formation may be mediated, in part, by deranged growth factor activity, including that of transforming growth factor (TGF)-β1. The addition of tamoxifen, a non-steroidal anti-estrogen, usually used in breast cancer, to standard treatment may lead to improved wound healing in keloids by decreasing the expression of TGF-β1, with the consequent inhibitions of both fibroblast proliferation and collagen production. Topical tamoxifen citrate chemical treatment has been shown to improve scarring. However, prospective studies must be undertaken to validate the inclusion of tamoxifen into standard clinical practice.
TL;DR: Optical coherence tomography assessment of psoriatic plaques may provide a useful method for non-invasive in vivo method to follow the evolution of psoriasis lesions and the measurements correlate with several other parameters of disease severity.
Abstract: Epidermal thickness (ET) has been suggested as a surrogate measure of psoriasis severity. Optical coherence tomography (OCT) is a recent imaging technology that provides real-time skin images to a depth of 1.8 mm with a micrometre resolution. OCT may provide an accurate in vivo measure of ET. It is, therefore, speculated that OCT may be used in the assessment of psoriasis vulgaris. A total of 23 patients with psoriasis vulgaris were systematically evaluated by OCT imaging and skin biopsy during treatment. Biopsies were graded for disease severity, and additional evaluation was done by the physician via psoriasis area and severity index (PASI) score, and by the patient through measures such as self-administered PASI, psoriasis life stress inventory index and dermatology life quality index. ET was calculated from OCT images. In comparison to normal skin, psoriasis appeared with a more irregular surface with a stronger entrance signal, a serrated dermo-epidermal junction was found and a less signal intensity in the dermis as shown in OCT images. ET measured in untreated plaques was thicker reflecting epidermal hyperproliferation and inflammation. The changes were significantly correlated with the biopsy grading (r (2) = 0.41, p = 0.001) and ET significantly decreased with treatment (p = 0.0001). ET correlated significantly with self-reported measures of disease severity, but not with physician-assessed global PASI. The data suggest that OCT may be used to measure ET in psoriasis and the measurements correlate with several other parameters of disease severity. This implies that OCT assessment of psoriatic plaques may provide a useful method for non-invasive in vivo method to follow the evolution of psoriasis lesions.
Journal Article•
TL;DR: The often unremarkable clinical presentation of NM necessitates physicians and patients to be wary of new or changing lesions and dermoscopy may help increase suspicion in early NM because dermoscopic features are typically more suggestive of malignancy than clinical ones.
Abstract: Background: Nodular melanoma (NM), representing 15% to 30% of all melanomas, constitutes nearly half of all melanomas thicker than 2 mm. Nodular melanoma frequently lacks clinical features seen in other melanoma subtypes and has a faster growth rate. We reviewed a series of cases of NM that was less than 1.3 mm thicktoidentifyhistorical,clinical,anddermoscopicfactors that may facilitate earlier diagnosis of NM, with the hope of reducing its associated morbidity and mortality. Observations:The thin NM lesions we analyzed had a rathersubtleclinicalappearance,oftenlackingtheABCD (asymmetry, border irregularity, color variegation, and diameter greater than 6 mm) criteria. On dermoscopy, mostlesionshadahomogeneousdisorganizedasymmetric pattern or a featureless pattern with atypical vessels. Althoughmanydermoscopicfeaturesseeninothermelanomasubtypeswerefrequentlyabsent,somefeaturessuch as a blue-white veil, structureless areas, and atypical vascular structures were often identified. Conclusions: The often unremarkable clinical presentation of NM necessitates physicians and patients to be wary of new or changing lesions. Dermoscopy may help increasesuspicioninearlyNMbecausedermoscopicfeatures are typically more suggestive of malignancy than clinical ones. We hope that secondary prevention efforts combined with prompt dermatologic consultations will allow for the timely diagnosis and management of NM. Arch Dermatol. 2010;146(3):311-318
TL;DR: The findings suggest that psoriasis is associated with bacteraemia, with distinct taxonomic groups present in guttate and chronic plaque psoriatic subtypes.
Abstract: Evidence exists that microorganisms, particularly in the throat and skin, play a role in the pathogenesis of psoriasis. The aim of this study was to investigate whether evidence for the presence of bacteria, including Streptococcus pyogenes, can be demonstrated in the peripheral blood of patients with guttate and/or chronic plaque psoriasis. Peripheral blood samples from 20 patients with psoriasis, seven guttate, six chronic plaque and seven chronic plaque with associated guttate flare and from 16 control subjects were studied for the presence of bacteria by PCR using universal 16S ribosomal DNA primers and specific primers for S. pyogenes. Sequence analysis of amplified 16S rRNA sequences was used to determine taxonomic identity. Ribosomal bacterial DNA was detected in the blood of all 20 patients with psoriasis, but in none of the controls. Streptococci were detected in six of seven patients with guttate psoriasis, but none had staphylococci. In contrast, staphylococci were identified in 9 of 13 patients with chronic plaque psoriasis, whilst only 2 demonstrated streptococci. In three psoriasis patients, species other than streptococci and staphylococci were identified. These findings suggest that psoriasis is associated with bacteraemia, with distinct taxonomic groups present in guttate and chronic plaque psoriatic subtypes. The causes of the bacteraemia and its implications in psoriasis have yet to be determined.
TL;DR: Subjects sustained a total of 18–21 months of wrinkle correction with a repeat treatment at 6–9 months and needed substantially less filler for repeat treatment than for initial treatment, indicating that retreatment at this timepoint may be beneficial to patients.
Abstract: Many patients elect to have repeat treatments with hyaluronic acid dermal fillers to maintain wrinkle correction, but the clinical performance of these products after repeat treatments has not been formally assessed. The primary objective of this study was to evaluate the effectiveness of Juvederm injectable gel (Juvederm Ultra, Juvederm Ultra Plus, and Juvederm 30) through 1 year after repeat treatment of nasolabial folds (NLFs) that were previously treated with Juvederm or Zyplast 6–9 months prior to the repeat treatment. Upon completion of the pivotal IDE clinical trial for Juvederm, five of the original 11 study sites were selected to participate in an extended follow-up evaluation, and a total of 80 subjects were enrolled. For the Juvederm-treated NLFs in each treatment group, the median injection volume was 1.5–1.6 mL for initial treatment but only 0.5–0.6 mL for the repeat treatment (p 24 weeks) and 0.7–0.9 (mild) at 4 weeks after repeat treatment. At 48 weeks post-repeat treatment, the mean NLF scores were 1.1–1.3 (mild), and 78–90% of subjects were considered responders (≥1 point improvement). Thus, subjects sustained a total of 18–21 months of wrinkle correction with a repeat treatment at 6–9 months and needed substantially less filler (60% less) for repeat treatment than for initial treatment, indicating that retreatment at this timepoint may be beneficial to patients.
TL;DR: Previous reports suggesting the potential role for CXCR3 in the pathophysiology of plaque psoriasis, by mediating the recruitment of plasmacytoid dendritic cells and T cells into the developing lesions are supported.
Abstract: In psoriasis, leukocytes that infiltrate skin lesions have been shown to be involved in the pathogenesis of this disease. Previous investigations reporting the presence of CXCR3(+) T lymphocytes in psoriatic lesional skin have suggested a role of this receptor in the recruitment of T cells into the lesion. The purpose of this study was to quantify the mRNA levels of CXCR3 and to perform a systematic analysis of the cell populations that express CXCR3 in human lesional and non-lesional psoriatic biopsies. We showed by real-time reverse transcriptase-polymerase chain reaction that the mRNA levels of CXCR3 and its ligands, CXCL9-11, were significantly elevated in psoriatic lesions, as compared to non-lesional samples. Serial cryostat sections of psoriasis skin biopsies were evaluated by immunohistochemistry. The number of CXCR3(+) cells was low in non-lesional tissues. Quantitative image analysis demonstrated significant increases in the number of both epidermal and dermal CXCR3(+) cells in lesional compared with non-lesional biopsies. The majority of CXCR3(+) cells were located in the dermis of the lesional skin and 74% were demonstrated to be CD3(+) T lymphocytes. A small number of CXCR3(+) cells were CD68(+) myeloid cells. In addition, we found that nearly all BDCA-2(+) plasmacytoid dendritic cells in the psoriatic biopsies were CXCR3(+). These findings support and extend prior reports suggesting the potential role for CXCR3 in the pathophysiology of plaque psoriasis, by mediating the recruitment of plasmacytoid dendritic cells and T cells into the developing lesions.
TL;DR: The studies demonstrate the presence of a permeability barrier abnormality in Sjögren–Larsson syndrome, which localizes to the stratum corneum interstices and can be attributed to abnormalities in lamellar body formation and secretion.
Abstract: Sjogren–Larsson syndrome is a genetic disease characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene coding for fatty aldehyde dehydrogenase, an enzyme necessary for oxidation of fatty aldehydes and fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with Sjogren–Larsson syndrome to better understand how the enzymatic deficiency results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion studies showed abnormal movement of tracer into the extracellular spaces of the stratum corneum consistent with a leaky water barrier. The barrier defect could be attributed to the presence of abnormal lamellar bodies, many with disrupted limiting membranes or lacking lamellar contents. Entombed lamellar bodies were present in the cytoplasm of corneocytes suggesting blockade of lamellar body secretion. At the stratum granulosum–stratum corneum interface, non-lamellar material displaced or replaced secreted lamellar membranes, and in the stratum corneum, the number of lamellar bilayers declined and lamellar membrane organization was disrupted by foci of lamellar/non-lamellar phase separation. These studies demonstrate the presence of a permeability barrier abnormality in Sjogren–Larsson syndrome, which localizes to the stratum corneum interstices and can be attributed to abnormalities in lamellar body formation and secretion.
TL;DR: Evaluated in vivo the effects of micropuncture injections of stabilized hyaluronic acid-based gel of non-animal origin (NASHA, Restylane Vital) on skin elasticity, a major aspect of skin ageing, and treatment with NASHA significantly increased skin firmness and improved its viscoelastic recovery capacities.
Abstract: The purpose of this study was to evaluate in vivo the effects of micropuncture injections of stabilized hyaluronic acid-based gel of non-animal origin (NASHA™, Restylane Vital™) on skin elasticity, a major aspect of skin ageing. Patients (n = 19) underwent a series of three treatment sessions, spaced 4 weeks apart, with NASHA injected into the lower facial cheeks. Using the suction principle, 12 parameters describing the viscoelastic properties of the skin were assessed, before each treatment session and at follow-up visits 4 and 16 weeks after the last treatment. Treatment with NASHA significantly increased skin firmness and improved its viscoelastic recovery capacities. The most significant differences from baseline were noted at the end of the study. The changes observed in this study may underlie some of the cosmetic improvements noted after treatment with NASHA.
TL;DR: Findings indicate that UVB stimulates functional KIT expression in human melanocytes via the up-regulation of MITF which is, in turn, due to the activation of p38 and CREB.
Abstract: KIT is an essential receptor that modulates melanocyte function and whose function is disrupted in several pigmentary disorders. However, little is known about the effects of a single UVB exposure on the expression of KIT and two important regulatory transcription factors, MITF and AP-2α, in human melanocytes. We found that a single UVB exposure of human melanocytes induces an early decrease and a subsequent increase in functional KIT expression in concert with up-regulated MITF expression. The increased MITF expression was accompanied by a markedly stimulated and prolonged phosphorylation of p38/CREB. The UVB-stimulated expression of KIT could be completely abolished by a p38 inhibitor, concomitant with a reduced phosphorylation of CREB and a down-regulation of MITF expression. Interestingly, in non-UVB exposed human melanocytes, a MEK inhibitor stimulated the phosphorylation of p38/CREB which was associated with an increased production of MITF and KIT in a pattern similar to that induced by UVB. These findings indicate that UVB stimulates functional KIT expression in human melanocytes via the up-regulation of MITF which is, in turn, due to the activation of p38 and CREB.
TL;DR: This review summarizes the current knowledge of the involvement of TJ and TJ proteins in mammalian skin in functions ascribed to TJ in simple epithelia, such as barrier function, polarity, gene expression, proliferation, differentiation, and vesicle transport.
Abstract: A variety of tight junction (TJ) proteins including claudins, occludin, tricellulin, zonula occludens-proteins and junctional adhesion molecules have been identified in complex localization patterns in mammalian epidermis. Their expression and/or localization is frequently altered in skin diseases including skin tumors. However, our understanding of the function(s) of TJ and TJ proteins in the skin is, even though rapidly increasing, still limited. This review summarizes our current knowledge of the involvement of TJ and TJ proteins in mammalian skin in functions ascribed to TJ in simple epithelia, such as barrier function, polarity, gene expression, proliferation, differentiation, and vesicle transport.
TL;DR: Therapies targeting vitamin D3 signaling may provide new approaches for infectious and inflammatory skin diseases by affecting both innate and adaptive immune functions.
Abstract: Constant exposure to a wide variety of microbial pathogens represents a major challenge for our skin. Antimicrobial peptides (AMPs) are mediators of cutaneous innate immunity and protect primarily against microbial infections. Cathelicidins were among the first AMPs identified in human skin and recent evidence suggests that they exert a dual role in innate immune defense: At first, due to their antimicrobial activity they kill pathogens directly. In addition, these peptides initiate a potent host response to infection resulting in cytokine release, inflammation and a cellular response. Disturbed cathelicidin expression and function was observed in several common inflammatory skin diseases, such as psoriasis where cathelicidin peptide converts inert self-DNA and self-RNA into an autoimmune stimulus. In atopic dermatitis decreased levels of cathelicidin facilitating microbial superinfections have been discussed. Furthermore, abnormally processed cathelicidin peptides induce inflammation and a vascular response in rosacea. Until recently, the molecular mechanisms underlying cathelicidin regulation were unknown. Recently, the vitamin D3 pathway was identified as the major regulator of cathelicidin expression. Consequently, vitamin D3 entered the spotlight as an immune modulator with impact on both innate and adaptive immunity. Therapies targeting vitamin D3 signaling may provide new approaches for infectious and inflammatory skin diseases by affecting both innate and adaptive immune functions.
TL;DR: Protection afforded by the extract of Rhodiola rosea L. roots to reduced glutathione levels, glyceraldehyde-3-phosphate dehydrogenase activity, and thiobarbituric acid reactive substances levels in cultured human keratinocytes exposed to different oxidative insults is measured.
Abstract: Keratinocytes are cells strongly exposed to oxidative stress, but normally good equipped for antioxidant responses. However, it has long been suggested that exogenous antioxidants could play a useful role in minimizing the adverse skin responses associated with such oxidant species. In this work it was paid attention to the extract of Rhodiola rosea L. roots by using the phytocomplex as a whole because of the important activity of its composition and mutual distribution of its components. We have measured the protection afforded by the extract to reduced glutathione levels, glyceraldehyde-3-phosphate dehydrogenase activity, and thiobarbituric acid reactive substances levels in cultured human keratinocytes (NCTC 2544) exposed to different oxidative insults: Fe(II)/ascorbate, Fe(II)/H(2)O(2), and tert-butyl-hydroperoxide. We also have investigated the influence of the R. rosea extract on the production of intracellular reactive oxygen species and on the activity of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase). Furthermore, we have demonstrated that R. rosea extract was able to increase in a time- and dose-dependent manner the activity of the trans plasma membrane oxido reductase activity as an indirect evaluation of the intracellular redox status and this effect was already evident with small concentration of the extract and in a long time. As a result, NCTC 2544 are able to better counteract to several oxidative insults if incubated with R. rosea extract demonstrating a very good antioxidant activity of this phytocomplex.
TL;DR: Culture of sebocytes provides a new insight into the participation of dihydrotestosterone (DHT) in the production of inflammatory cytokines in acne and suggests that DHT may not only be involved in sebum production but also in production of proinflammatory cytokine in acne.
Abstract: Acne is a complex, chronic and common skin disorder of pilosebaceous units. Hyperkeratinization of keratinocytes, increased sebum excretion from sebocytes via androgen stimulation and inflammatory cytokines are the major factors involved in the pathophysiology of acne. In addition, it is known that keratinocytes play an important role in acne synthesizing a number of inflammatory cytokines. However, the nature of the association between inflammatory cytokines and sebocytes in acne remains unclear. Culture of sebocytes provides a new insight into the participation of dihydrotestosterone (DHT) in the production of inflammatory cytokines in acne. To examine the possible involvement of DHT in the production of inflammatory cytokines in the cultured sebocytes, we used immunohistochemistry and RT-PCR to compare the expression of interleukin-1 (IL-1), IL-6, tumor necrosis factor-α (TNF-α). Upregulation of IL-6 and TNF-α in immunohistochemistry, and increase in RNA amplification for IL-6 and TNF-α were observed after addition of DHT compared with the control. This study suggests that DHT may not only be involved in sebum production but also in production of proinflammatory cytokines in acne.
TL;DR: It is found that the same mutation could lead to different phenotypes even in the same family and did not establish a clear correlation between genotypes and phenotypes, useful for functional studies of the protein and to define a diagnostic strategy for mutation screening of the ADAR1 gene.
Abstract: Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant cutaneous disorder characterized by a mixture of hyperpigmented and hypopigmented macules of various sizes on the extremities and caused by the mutations of adenosine deaminase acting on RNA1 (ADAR1) gene. We screened 14 unrelated families or sporadic cases for mutation in the full coding sequence of this gene. Eight novel heterozygous mutations of ADAR1 and four known mutations were identified, including four missense mutations (p.R26K, p.Y1192D, p.R916Q, p.R1155W), six frameshift mutations (p.N205fsX217, p.V211fsX217, p.V404fsX417, p.I914fsX927, p.L1053fsX1076, p.L1070fs1092), and two nonsense mutations (p.R474X, p.R1096X). Interestingly, we failed to detect any mutations of ADAR1 in one family. Including our data, there are now 93 different mutations reported in 105 independent patients that we have tabulated. From the review of clinical features in these reports, we found that the same mutation could lead to different phenotypes even in the same family and did not establish a clear correlation between genotypes and phenotypes. Finally this study is useful for functional studies of the protein and to define a diagnostic strategy for mutation screening of the ADAR1 gene.