The Journal of investigative dermatology
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J. Invest. Dermatol. · Aug 2015
Comparative StudyDifferential Changes in the Peptidergic and the Non-Peptidergic Skin Innervation in Rat Models for Inflammation, Dry Skin Itch, and Dermatitis.
Skin innervation is a dynamic process that may lead to changes in nerve fiber density during pathological conditions. We have investigated changes in epidermal nerve fiber density in three different rat models that selectively produce chronic itch (the dry skin model), or itch and inflammation (the dermatitis model), or chronic inflammation without itch (the CFA model). In the epidermis, we identified peptidergic fibers-that is, immunoreactive (IR) for calcitonin gene-related peptide or substance P—and non-peptidergic fibers—that is, IR for P2X3. ⋯ In contrast, the density of epidermal non-peptidergic fibers was not increased, except for a small but significant increase in the dry skin model. Chronic inflammation showed an increased density of peptidergic fibers without itch, indicating that increased nerve fiber density is not invariably associated with itch. The finding that different types of skin pathology induced differential changes in nerve fiber density may be used as a diagnostic tool in humans, through skin biopsies, to identify different types of pathology and to monitor the effect of therapies.
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J. Invest. Dermatol. · May 2015
Review Meta AnalysisPlacebo effects on itch: a meta-analysis of clinical trials of patients with dermatological conditions.
Although placebo contributes to the effects of treatment for various symptoms and conditions, its effect on itch has rarely been investigated. In this meta-analysis, the magnitude of the placebo effect on itch was systematically investigated in clinical trials including patients with chronic itch due to atopic dermatitis, psoriasis, or chronic idiopathic urticaria. From searches in four databases, 34 articles were included in the quantitative analyses. Placebo treatment significantly decreased itch (1.3 out of 10, 95% confidence interval 1.02-1.61) compared with baseline itch (effect size 0.55), indicating that placebo effects have a considerable role in these patients' treatment.
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J. Invest. Dermatol. · Apr 2015
Protective effect of MFG-E8 after cutaneous ischemia-reperfusion injury.
We recently demonstrated that the secreted glycoprotein and integrin-ligand MFG-E8 promotes cutaneous wound healing by enhancing angiogenesis. Several studies have identified potential roles for MFG-E8 in regulation of ischemia-reperfusion (I/R) injury in the brain, kidney, and liver. Our objective was to assess the role of MFG-E8 in the formation of skin ulcers using a murine model of cutaneous I/R injury-cutaneous pressure ulcers. ⋯ The number of M1 macrophages and the amount of proinflammatory mediators monocyte chemotactic protein-1,induced nitric oxide synthase, IL-6, tumor necrosis factor-α, and IL-1β in the wound area were reduced by the administration of rMFG-E8. We conclude that MFG-E8 may inhibit the formation of pressure ulcers induced by cutaneous I/R injury by regulating angiogenesis and inflammation. Exogenous application of MFG-E8 might have therapeutic potential for cutaneous I/R injuries, including decubitus ulcers and Raynaud's phenomenon-induced digital ulcers.
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J. Invest. Dermatol. · Feb 2015
Identification of p38β as a therapeutic target for the treatment of Sézary syndrome.
Cutaneous T-cell lymphomas (CTCLs) represent a group of hematopoietic malignancies that home to the skin and have no known molecular basis for disease pathogenesis. Sézary syndrome (SS) is the leukemic variant of CTCL. Currently, CTCL is incurable, highlighting the need for new therapeutic modalities. ⋯ Further analysis identified p38 as a potential therapeutic target that is overexpressed in SS patients and decreased by synergistic-inhibitor treatment. This target was verified through small-molecule inhibition of p38, leading to cell death in both SS cell lines and patient cells. These data establish p38 as a SS biomarker and a potential therapeutic target for the treatment of CTCL.