Photoprotection Lautenschlager, Stephan, Dr; Wulf, Hans Christian, Prof; Pittelkow, Mark R, Prof
Lancet,
08/2007, Volume:
370, Issue:
9586
Journal Article, Book Review
Peer reviewed
Summary Sun exposure is the main cause of photocarcinogenesis, photoageing, and photosensitivity; thus, photoprotection is an important issue. In a skin cancer prevention strategy, behavioural ...measures—eg, wearing sun protective clothes and a hat and reducing sun exposure to a minimum—should be preferred to sunscreens. Often this solution is deemed to be unacceptable in our global, outdoor society, and sunscreens could become the predominant mode of sun protection for various societal reasons (eg, healthiness of a tan, relaxation in the sun). The application of a liberal quantity of sunscreen has been shown to be by far the most important factor for effectiveness of the sunscreen, followed by the uniformity of application and the specific absorption spectrum of the agent used. The sunscreen market—crowded by numerous products—shows various differences worldwide. Nevertheless, sunscreens should not be abused in an attempt to increase time in the sun to a maximum. Controversies about safety of sunscreens and clinical recommendations are discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A Mayo Clinic analysis of melanoma distribution showed a high frequency of lesions on the heel and fewer lesions on the front of the foot than shown in a Japanese study that indicated that melanomas ...may be most common in weight-bearing areas of the plantar surface.
Background Calciphylaxis is characterized by ischemic cutaneous ulceration, high mortality, and ineffective treatment. Methods We conducted a retrospective study of 64 patients with calciphylaxis ...(including 49 dialysis patients age- and sex-matched to 98 dialysis controls). Results The estimated 1-year survival rate of calciphylaxis was 45.8%. Risk factors for calciphylaxis included obesity, liver disease, systemic corticosteroid use, calcium-phosphate product more than 70 mg2 /dL2 , and serum aluminum greater than 25 ng/mL. Survival rates were similar for 16 patients who received parathyroidectomy and 47 who did not. An estimated 1-year survival rate of 61.6% was observed for 17 patients receiving surgical debridement compared with 27.4% for the 46 who did not ( P = .008). Limitations The study was limited by its retrospective design and there was no control group for the 15 nondialysis cases. Conclusions Calciphylaxis is multifactorial and usually fatal. Prevention of calciphylaxis may include correction of risk factors identified in this study. Surgical debridement was associated with improved survival, but parathyroidectomy was not.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To report on the survival and the associations of treatments upon survival of patients with calciphylaxis seen at a single center.
Using the International Classification of Diseases, Ninth Revision ...diagnosis code of 275.49 and the keyword "calciphylaxis" in the dismissal narrative, we retrospectively identified 101 patients with calciphylaxis seen at our institution between January 1, 1999, through September 20, 2014, using a predefined, consensus-developed classification scheme.
The average age of patients was 60 years: 81 (80.2%) were women; 68 (68.0%) were obese; 19 (18.8%) had stage 0 to 2 chronic kidney disease (CKD), 19 (18.9%) had stage 3 or 4 CKD; 63 (62.4%) had stage 5 or 5D (dialysis) CKD. Seventy-five patients died during follow-up. Six-month survival was 57%. Lack of surgical debridement was associated with insignificantly lower 6-month survival (hazard ratio HR=1.99; 95% CI, 0.96-4.15; P=.07) and significantly poorer survival for the entire duration of follow-up (HR=1.98; 95% CI, 1.15-3.41; P=.01), which was most pronounced in stage 5 or 5D CKD (HR=1.91; 95% CI, 1.03-3.56; P=.04). Among patients with stage 5/5D CKD, subtotal parathyroidectomy (performed only in patients with hyperparathyroidism) was associated with better 6-month (HR=0.12; 95% CI, 0.02-0.90; P=.04) and overall survival (HR= 0.37; 95% CI, 0.15-0.87; P=.02).
Calciphylaxis is associated with a high mortality rate. Significantly effective treatments included surgical debridement and subtotal parathyroidectomy in patients with stage 5/5D CKD with hyperparathyroidism. Treatments with tissue-plasminogen activator, sodium thiosulfate, and hyperbaric oxygen therapy were not associated with higher mortality.
Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while ...many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The presence of an autocrine adrenergic and cholinergic intra/intercellular signal transduction network in the human epidermis contributes significantly to homeostatic and compensatory responses ...regulating vital functions in keratinocytes and melanocytes. The ligands produced control autocrine and paracrine loops to initiate responses through cognate receptors expressed within the same or adjacent cells. The epidermal adrenergic signal controls calcium homeostasis, cell growth, differentiation, motility, and pigmentation via the β2 and α1 adrenoceptors. The cholinergic system is highly complex comprising both nicotinic and muscarinic receptors with multiple subtypes and this system plays an important role in keratinocyte cell cycle progression, differentiation, directional migration, adhesion, and apoptotic secretion. Moreover, lymphocytes also express adrenergic and cholinergic receptors. Both types of signal transduction receptors are coupled to classical intracellular second messenger pathways, including cAMP-, cGMP-, and calcium-mediated downstream responses. To date, it has been recognized that several dermatoses such as psoriasis, atopic dermatitis, Mal de Meleda, vitiligo, palmoplantar pustulosis, and pemphigus may be mediated, in part, by the non-neuronal adrenergic/cholinergic systems. A detailed understanding of the physiology and pathophysiology of the adrenergic/cholinergic network in the skin could offer the development of specific drugs for novel treatment modalities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pemphigus vulgaris (PV) is a mucocutaneous blistering disease characterized by IgG autoantibodies against the stratified squamous epithelium. Current understanding of PV pathophysiology does not ...explain the mechanism of acantholysis in patients lacking desmoglein antibodies, which justifies a search for novel targets of pemphigus autoimmunity. We tested 264 pemphigus and 138 normal control sera on the multiplexed protein array platform containing 701 human genes encompassing many known keratinocyte cell-surface molecules and members of protein families targeted by organ-non-specific PV antibodies. The top 10 antigens recognized by the majority of test patients' sera were proteins encoded by the DSC1, DSC3, ATP2C1, PKP3, CHRM3, COL21A1, ANXA8L1, CD88 and CHRNE genes. The most common combinations of target antigens included at least one of the adhesion molecules DSC1, DSC3 or PKP3 and/or the acetylcholine receptor CHRM3 or CHRNE with or without the MHC class II antigen DRA. To identify the PV antibodies most specific to the disease process, we sorted the data based on the ratio of patient to control frequencies of antigen recognition. The frequency of antigen recognition by patients that exceeded that of control by 10 and more times were the molecules encoded by the CD33, GP1BA, CHRND, SLC36A4, CD1B, CD32, CDH8, CDH9, PMP22 and HLA-E genes as well as mitochondrial proteins encoded by the NDUFS1, CYB5B, SOD2, PDHA1 and FH genes. The highest specificity to PV showed combinations of autoantibodies to the calcium pump encoded by ATP2C1 with C5a receptor plus DSC1 or DSC3 or HLA-DRA. The results identified new targets of pemphigus autoimmunity. Novel autoantibody signatures may help explain individual variations in disease severity and treatment response, and serve as sensitive and specific biomarkers for new diagnostic assays in PV patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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