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    ABSTRACT: A 49-year-old Caucasian male was referred to the Manchester Psoriasis Service with a 21-year history of severe chronic plaque psoriasis refractory to therapy with topical agents, phototherapy (TL-01), systemic agents (methotrexate, ciclosporin and fumaderm) and the biologic agents adalimumab and ustekinumab, including with concurrent ciclosporin therapy. Relevant history included alcohol excess. There was no family history of demyelination. Following a flare of psoriasis in June 2011, treatment was changed from ustekinumab (90mg dosing regimen) with ciclosporin 2mg/kg/day, to infliximab IV (5mg/kg at week 0, 2, 6, thereafter at 8 week intervals). This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 01/2014; 170(1).
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    ABSTRACT: Eicosapentaenoic acid (EPA), abundant in oily fish, is reported to reduce skin inflammation and provide photoprotection, potential mechanisms include competition with arachidonic acid (AA) for metabolism by cyclooxygenases/lipoxygenases to less pro-inflammatory mediators. We thus examine impact of EPA intake on levels of AA, EPA and their resulting eicosanoids in human skin with or without ultraviolet radiation (UVR) challenge. In a double-blind randomised controlled study, 79 females took 5 g EPA-rich or control lipid for 12 wk. Pre- and post-supplementation, red blood cell and skin polyunsaturated fatty acids were assessed by GC, and eicosanoids from unexposed and UVR-exposed skin by LC-MS/MS. Active supplementation increased red blood cell and dermal EPA versus control (both p < 0.001), lowering relative AA:EPA content (4:1 versus 15:1 and 5:1 versus 11:1, respectively; both p < 0.001). Pre-supplementation, UVR increased PGE2 , 12-hydroxyeicosatetraenoic acids, 12-HEPE (all p < 0.001) and PGE3 (p < 0.05). Post-EPA, PGE2 was reduced in unchallenged skin (p < 0.05) while EPA-derived PGE3 (non-sign) and 12-HEPE (p < 0.01) were elevated post-UVR. Thus, post-EPA, PGE2 :PGE3 was lower in unchallenged (12:1 versus 28:1; p < 0.05) and UVR exposed (12:1 versus 54:1; p < 0.01) skin; 12-hydroxyeicosatetraenoic acids:12-HEPE was lower in UVR-exposed skin (3:1 versus 11:1; p < 0.001). Dietary EPA augments skin EPA:AA content, shifting eicosanoid synthesis towards less pro-inflammatory species, and promoting a regulatory milieu under basal conditions and in response to inflammatory insult.
    Molecular Nutrition & Food Research 12/2013;
  • Nature 12/2013; 504(7478):33.
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    ABSTRACT: For over a century, frogs have been studied across various scientific fields, including physiology, embryology, neuroscience, (neuro)endocrinology, ecology, genetics, behavioural science, evolution, drug development, and conservation biology. In some cases, frog skin has proven very successful as a research model, for example aiding in the study of ion transport through tight epithelia, where it has served as a model for the vertebrate distal renal tubule and mammalian epithelia. However, it has rarely been considered in comparative studies involving human skin. Yet, despite certain notable adaptations that have enabled frogs to survive in both aquatic and terrestrial environments, frog skin has many features in common with human skin. Here we present a comprehensive overview of frog (and toad) skin ontogeny, anatomy, cytology, neuroendocrinology and immunology, with special attention to its unique adaptations as well as to its similarities with the mammalian integument, including human skin. We hope to provide a valuable reference point and a source of inspiration for both amphibian investigators and mammalian researchers studying the structural and functional properties of the largest organ of the vertebrate body.
    Biological Reviews 12/2013;
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    Dermatology and therapy. 12/2013;
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    ABSTRACT: Skin cancer is a major public health concern and the primary aetiological factor in the majority of skin cancers is UVR exposure. Ultraviolet radiation not only induces potentially mutagenic DNA damage, but also suppresses cell mediated immunity (CMI), allowing cancerous cells to escape destruction and progress to tumours. A considerable proportion of an individual's annual sun exposure is obtained outside the vacation period when topical and physical measures for photoprotection are irregularly used. Certain nutrients could provide an adjunctive protective role and evidence is accruing from experimental studies to support their use in abrogation of photoimmunosuppression. Moreover, developments in clinical research methods to evaluate impact of solar simulated radiation on cutaneous CMI allow the immune protective potential of nutritional agents to be examined in humans in vivo. This article summarises the mediation of CMI and its suppression by UVR, evaluates the methodology for quantitative assessment in vivo, reviews the human studies reported on nutritional abrogation of photoimmunosuppression including recent randomised controlled trials, and discusses the mechanisms of photoprotection by the nutrients. This includes, in addition to antioxidants, novel studies of omega-3 polyunsaturated fatty acids and nicotinamide.
    Photodermatology Photoimmunology and Photomedicine 11/2013;
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    ABSTRACT: Photodynamic therapy (PDT) is an established treatment for superficial basal cell carcinoma (BCC). Organ transplant recipients (OTRs) are at increased risk of BCC. We investigated the efficacy of PDT in OTRs and compared the recurrence rate to the non-transplanted population. We conducted a retrospective casenote review of all patients undergoing PDT for the treatment of BCC in our centre from 2003 to 2013. Three hundred and twenty-two BCCs from 103 patients underwent PDT during this period. There is no significant difference in BCC recurrence following PDT in OTRs (22.6 %) versus non-transplant patients (15.2 %) (p = 0.18). PDT is an efficacious treatment for BCC in OTRs with no significant evidence of inferiority compared to non-transplanted patients. Our findings require corroboration in a larger study.
    Lasers in Medical Science 10/2013;
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    ABSTRACT: Currently, efficacious treatments for chemotherapy-induced alopecia (hair loss) are lacking, and incidences of permanent hair loss following high-dose chemotherapy are on the increase. In this article, we describe mechanisms by which the pharmacological defense status of the hair follicle might be enhanced, thereby reducing the accumulation of cytotoxic cancer drugs and preventing or reducing hair loss and damage. We believe this could be achieved via the selective increase in ATP-binding cassette (ABC) transporter expression within the hair follicle epithelium, following application of topical agonists for regulatory nuclear receptors. Clinical application would require the development of hair follicle-targeted formulations, potentially utilizing nanoparticle technology. This novel approach has the potential to yield entirely new therapeutic options for the treatment and management of chemotherapy-induced alopecia, providing significant psychological and physical benefit to cancer patients.
    Trends in Pharmacological Sciences 10/2013;
  • Journal of Crohn s and Colitis 09/2013;
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    ABSTRACT: The hair follicle (HF) is a continuously remodelled mini-organ that cycles between growth (anagen), regression (catagen) and relative quiescence (telogen). Since the anagen-catagen transformation of micro-dissected human scalp HFs can be observed in organ culture permits the study of the unknown controls of autonomous, rhythmic tissue remodelling of the HF which intersects developmental, chronobiological and growth-regulatory mechanisms. The hypothesis, that the peripheral clock system is involved in the hair cycle transition, i.e. the anagen-to-catagen transformation, was tested. We show that, in the absence of central clock influences, isolated, organ-cultured human HFs show circadian changes in the gene and protein expression of core clock genes (CLOCK, BMAL1, Period1) and clock-controlled genes (c-Myc, NR1D1, CDKN1A), with Period1 expression being hair cycle-dependent. Knock-down of either BMAL1 or Period1 in human anagen HFs significantly prolonged. This provides evidence that peripheral core clock genes modulate human HF cycling, and are an integral component of the human hair cycle clock. Specifically, our study identifies BMAL1 and Period1 as potential therapeutic targets for modulating human hair growth.Journal of Investigative Dermatology accepted article preview online, 4 September 2013; doi:10.1038/jid.2013.366.
    Journal of Investigative Dermatology 09/2013;
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