MC1R pathways) would provide an up-to-date, superior mouse model able to mimic molecular aetiology of human melanoma to investigate the functions and mechanisms of other genes such as MITF, B-Raf, MC1R etc involved in the development of human melanoma.

The mechanism of action of IPL in acne treatment is not clearly understood, but an immunomodulatory role has been suggested. Furthermore, inflammatory cytokines and matrix degrading enzymes play a key role in acne pathogenesis. Therefore, curbing the production of these mediators may assist acne resolution. In photorejuvenation studies, IPL has been shown to induce the expression of a key immunomodulatory cytokine, TGF-β. Interestingly, TGF-β has been demonstrated to mediate immunosuppression, inhibition of keratinocyte proliferation and MMP-1 repression through a Smad3-mediated signalling pathway. Therefore, we sought to investigate the in vivo effects of IPL used for acne treatment. Biopsies obtained from 20 patients with inflammatory acne vulgaris at baseline and post-IPL treatment (48 hrs after the first treatment and 1 week after the final treatment) were immunohistochemically analysed to investigate the expression of TGF-β1, TGF-β2, TGF-β3, Smad3, MMP-1 and IL-8. Digital images were semi-qualitatively assessed using image analysis software. In addition, quantitative PCR analysis of TGF-β1, Smad3 and IL-8 was performed on biopsies from seven cases. Immunohistochemical analysis demonstrated that IPL elicited a statistically significant increase in epidermal TGF-β1 expression. However, no statistically significant difference was observed in the expression of TGF-β2/β3. Increased nuclear immunolocalisation of Smad3 was demonstrated in the post-IPL biopsies, which was statistically significant. Although not statistically significant, both IL-8 and MMP-1 expression showed a downward trend in the majority of cases. No statistically significant change was detected in the gene expression of TGF-β1, Smad3 and IL-8, which may be attributed to the small sample in which PCR was carried out. The data from this study suggests that Smad3-mediated TGF-β1 signalling may play a role in IPL-induced resolution of acne vulgaris. The therapeutic effect of TGF-β1 in inflammatory acne vulgaris could be attributed to its immunosuppressive effect and its ability to inhibit matrix degradation and keratinocyte proliferation.

Thyroid dysfunction is frequently associated with skin and hair diseases; however, the underlying pathogenic mechanisms are poorly understood. Pathological activation of the thyroid stimulating hormone receptor (TSHR) is the key feature of both hyper- and hypo-thyrodism. Expression of the (TSHR) has been reported in several extra-thyroidal locations including adipose tissue, bone and skin fibroblasts. TSHR expression may explain the association between the thyroid and skin disease. The TSHR can also be activated by a newly discovered glycoprotein hormone, known as thyrostimulin. This hormone is composed of a dimer of unique α 2 and β 5 subunits. Although thyrostimulin has not been detected in the circulation. However, both subunits have been shown to be expressed in different tissues including the skin. The aim of this study is to examine the expression of the TSHR and thyrostimulin in the skin. In addition, to investigate the expression of a variant form of the TSHR in human and mouse skin and, other mouse tissues. RT-PCR using primers specific for the full length receptor and the truncated variant revealed that although the variant was widely expressed in mouse tissues including skin, it was not found in human skin. The full length receptor and thyrostimulin were found to be co-expressed in eye, testis and skin. Immunohistochemistry of frozen skin and thyroid sections using commercially available antibodies against the extracellular (A9) and transmembrane domains (A7) of TSHR demonstrates that TSHR is not expressed in the epidermis but expressed in dermal fibroblasts and in myoepithelium around sweat glands. A new β5 antibody was characterised by western blotting and immunohistochemistry for future investigation of β5 expression in the skin. These data suggest a functional role for TSHR signalling possibly via thyrostimulin in the skin and that the variant form,although potentially present in some tissues, is unlikely to be important in human skin.

Human skin forms a biologically active barrier and maintains vital protective functions through continuous regeneration of cells within its outermost layer, the epidermis. In healthy skin, renewal of epithelial cells is a tightly regulated process in which the epidermal growth factor receptor (EGFR or HER1) and its various ligands are involved. The biological role of other EGFR family members (HER2–4) in normal and diseased human skin has gained less interest. The purpose of this work was to investigate the expression and contribution of different HERs in cultured epidermis and psoriatic skin. Epidermal regeneration was studied by fluorescence imaging of a skin explant model exposed to anti-psoriatic drugs, HER ligands or HER-blocking molecules. EGFR, HER2 and HER3 were all markedly expressed with an in vivo-like immunostaining pattern in cultured neoepidermis, whereas only low amounts of HER4 were detected at protein and mRNA levels. Re-epithelialization was associated with receptor activation. Application of HER-selective tyrosine kinase inhibitors and monoclonal antibodies reduced the proliferative activity, receptor phosphorylation and radial outgrowth from normal skin explants. Similar anti-dynamic effects were obtained with HER kinase inhibition of neoepidermis generated from psoriatic skin. Among the HER receptors, EGFR seemed to be the dominant subtype during epithelialization in vitro although HER2 and HER3 were also involved. HER2 probably functioned as a co-receptor for the kinase-deficient HER3 in neoepidermis. In vivo, expression of HER4 mRNA was detected in normal and uninvolved psoriatic skin but was virtually absent in lesional skin, a potentially important finding for HER signalling in psoriasis. This thesis demonstrates the utility of combined dynamic and biochemical analyses of re-epithelialization and highlights the role of EGFR and other HERs for epidermal growth. It also underscores the potential of HER-directed inhibition to control hyperproliferative states of the epidermis.

- / -

Data from studies looking at the use of systemic vitamin D and omega-3 fatty acids independently in the treatment of psoriasis has shown that both these supplements have at least a modest effect when taken in above average doses. Recent advances in the understanding of the pathophysiology of psoriasis as well as the immunomodulatory and anti-inflammatory properties of these supplements suggest that they could have an additive effect in treating this life-long disease. The proposed study is a randomized placebo-controlled trial that aims to explore this supposition by supplying demographically diverse subjects, who have varying levels of psoriasis severity, with 4g of Omacor® fish oil (1.8g EPA + 1.5g DHA) and 4000IU of vitamin D3 (cholecalciferol) or placebo pills on top of their existing treatment regimen. The subjects will have a baseline evaluation and the trial will run for 1 year with 12 week follow up intervals. Every 12 weeks the subjects will have a clinician calculate their current PASI score and have blood drawn to measure vitamin D levels. Investigators will analyze the overall percent reduction of an individual’s PASI score as well as the mean final PASI scores of the intervention and control groups. The data from this study will provide information that could add another safe, inexpensive, and effective treatment modality to the dermatologist’s arsenal.

INTRODUCTION: Vulvar lichen sclerosus (LS) is characterized by thinning of the epithelium, and whitening of the vulvar skin which can lead to the characteristic symptoms of burning and itching. There is no cure for vulvar LS and topical corticosteroids are first-line treatment. The aims of this thesis are to propose a study to determine whether topical combination therapy with an ultra-potent corticosteroid and calcineurin inhibitor leads to greater improvement in symptoms and clinical appearance of disease than traditional first-line treatment with an ultra-potent corticosteroid alone, and to evaluate relapse rates between the combination therapy group compared to the topical corticosteroid only group. REVIEW OF LITERATURE: The ultra-potent corticosteroid clobetasol propionate is currently the first-line treatment for women with LS however not all patients achieve remission, and many patients have relapses. Topical calcineurin inhibitors such as tacrolimus are considered to be second-line treatments for vulvar LS and may eliminate the side effects of thinning that can occur with long-term therapy with corticosteroids. METHODS: A single-center randomized control trial will be conducted with post-menopausal women recruited from the dermatology and gynecology at Boston Medical Center. The patients will be randomized to either three months treatment with daily clobetasol propionate in the morning and tacrolimus ointment in the evening, or clobestasol propionate in the morning with a vehicle ointment in the evening. The patients will be evaluated for improvement in symptoms of burning and itching, and for clinical appearance of erythema, whitening of the skin, and hyperkeratosis, purpuric lesions and excoriations. The patients will also be followed for a year post-treatment for signs of relapse. CONCLUSION: The incidence of vulvar LS is increasing and may be under-reported. Though corticosteroids are an effective treatment for most patients, combination therapy with topical tacrolimus may increase the proportion of patients who achieve remission for vulvar LS and will improve their quality of life.

Thesis (M.A.)--Boston University

This thesis sets out to demonstrate the significant contribution to the field of podiatric dermatology, through the use of various forms of published documentary evidence, made by the author. In addition to the published papers submitted, a content analysis of British podiatric literature over a period of 21 years has mapped the emergence and development of the specialism of podiatric dermatology within the United Kingdom. This work demonstrates a significant increase in professional interest within this area during this period. This is evidenced through increased reporting of dermatological topics within podiatry journals in terms of related news items, advertisements and editorials. This is accompanied by an increasing number of case studies, peerreviewed papers and continuing professional development articles evident within the literature. The author has presented within this thesis a suite of fifty published articles along with verifiable evidence of professional activities related to the promotion and development of podiatric dermatology. Collectively this evidence represents a significant contribution to the development and evolution of dermatology as a specialist area within podiatry in the United Kingdom over the last fifteen years.

Anaplastic large-cell lymphoma (ALCL) is a CD30 + lymphoproliferative disorder that may manifest with skin involvement.1 We present a rare case of Agent Orange-induced ALCL with cutaneous involvement of the hand, surgical excision, and follow-up treatment.