The combination of optical clearing and LSFM has new applications in dermatology and dermatological research by allowing 3D visualization and analysis of whole human skin biopsies.
OBJECTIVE: The main function of skin is to protect the body from external aggressions. Over time, normal skin ageing is accelerated by external stresses such as smoking, pollution, chemical products and radiation. UV light, in particular UVA, causes DNA damage, apoptosis and morphological modifications, which are responsible for both premature ageing and cancer. The aim of this study was to establish a discriminatory and sufficiently reproducible cutaneous model for evaluating UVA damage, to enable testing for effectiveness of potentially protective compounds. METHODS: The cutaneous model is based on Human skin explants irradiated with UVA. Deleterious effects on epidermis were observed and quantified by haematoxylin-eosin staining and by immunofluorescence of ɣ-H2Ax, cytokeratin 5, involucrin and loricrin protein. Dermis deterioration was evaluated by transmission electronic microscopy and zymography in situ. RESULTS:We were able to observe and quantify deleterious effects associated with UVA irradiation: epidermal and dermal disruption, appearance of Sunburn cells, increased DNA damage and induced apoptosis. The use of this model in the evaluation of protective compounds was first confirmed using sunscreens, then further validated with a panel of active ingredients which showed beneficial effects on epidermis morphology and DNA integrity after UVA exposure. CONCLUSION: We have developed a model and a standardized protocol, based on the use of human skin explants,
Dermatomyositis-related panniculitis (DP) manifests as red subcutaneous, firm and tender plaques, usually on the arms, buttocks, thighs and abdomen. DP is commonly described in textbooks yet there are few reports in the medical literature and there are no guidelines on its best management. Here we present a case of a patient with DP of the neck region. Case Description: A 66-year-old African American woman with a three-year history of dermatomyositis with high titer antinuclear antibody, characteristic pattern of rash, and muscle weakness presented with progressive neck swelling, neck pain, dysphagia, and dyspnea over a period of two months. Physical examination revealed extensive woody induration of the anterior neck region, mild tenderness on palpation on the right side, and decreased range of motion of the neck. CT scan demonstrated extensive soft tissue infiltration in the neck and mediastinum, pleural thickening, as well as a new 1.5 centimeter right lower lobe pulmonary nodule with irregular borders not previously seen on CT scan three months prior. PET scan demonstrated inflammation throughout the mediastinum and into the chest, but no area demonstrated significant avidity consistent with cancer. Flow cytometry was also negative. Histological examination of a neck biopsy demonstrated lobular panniculitis. Based on the histological appearance, a diagnosis of DP was made. Treatment with corticosteroids, dapsone, and colchicine resolved the DP and controlled the dermatomyositis symptoms. Repeat CT scan showed largely complete resolution of the pleural thickening, pulmonary nodule, and mediastinal mass. Conclusion: While cutaneous involvement of dermatomyositis is well described, subcutaneous involvement is a rarely reported clinical finding. This is the first report describing DP in the neck and mediastinal region. The parallel response to corticosteroids in the panniculitis and myositis suggest these processes share a related pathogenesis.
Background Klotho is a protein known for its beneficial effects on longevity. Centcyamine is an alkaloid present in certain plants whose extracts have an anti‐inflammatory effect. Skin fibroblasts are essential to the formation and structure of the dermis. Objective Centcyamine is an indole‐based alkaloid composed of coumaric acid, a resveratrol precursor and methoxytryptamine, which can be both a precursor, or a derivative, of melatonin. Given these building blocks and their well‐known bioactivities, it was of interest to explore the potential benefits of using this aryl‐alkaloid, in cosmetic skincare applications. Methods We tested cultured normal human dermal fibroblasts (NHDF) in vitro to observe how supplementation with centcyamine improves properties of the cells to counteract the effect of ageing. The expression of genes and proteins of interest was quantified. The effect on doubling time and cell function was evaluated following treatment of the cells over several replication cycles. Skin firmness, red spot index and skin isotropy were measured with Dynaskin®, Visia® and Primos® equipment, respectively, and compared over two months in a vehicle‐controlled clinical trial on 60 persons. Results Centcyamine activates the expression of the gene KL and the related protein Klotho in dermal fibroblasts. Moreover, centcyamine slows the replicative ageing process of fibroblasts in culture. These cells retain cellular functions identical to those of young cells: the synthesis of lamin B1, a crucial regulatory protein of proliferation, as well as of collagen I and elastin is retained in aged cells. The clinical data are shown to improve skin isotropy in a majority of subjects, to reduce the red spot intensity and to maintain skin firmness in the treated group vs. the vehicle. Conclusion The alkaloid centcyamine induces changes in the metabolism of the ageing process of human dermal fibroblasts. The up‐to‐now unobserved implication of both Klotho and lamin B1 to maintain homeostasis of the skin opens new venues for the prevention of age‐related changes in skin structure. The in vitro and clinical data, while not demonstrated to be causally related, converge towards a common goal of skin repair and slower ageing processes.
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