Experimental dermatology
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Experimental dermatology · Aug 2005
DeoxyArbutin: a novel reversible tyrosinase inhibitor with effective in vivo skin lightening potency.
Modulation of melanogenesis in the melanocytes can be achieved using chemicals that share structural homologies with the substrate tyrosine and as thus competitively inhibit the catalytic function of tyrosinase. We have developed a new tyrosinase inhibitor, deoxyArbutin (dA), based on this premise. DeoxyArbutin demonstrates effective inhibition of mushroom tyrosinase in vitro with a Ki that is 10-fold lower that hydroquinone (HQ) and 350-fold lower than arbutin. ⋯ Results from a panel of safety tests supported the overall establishment of dA as an actionable molecule. In a human clinical trial, topical treatment of dA for 12 weeks resulted in a significant or slight reduction in overall skin lightness and improvement of solar lentigines in a population of light skin or dark skin individuals, respectively. These data demonstrate that dA has potential tyrosinase inhibitory activity that can result in skin lightening and may be used to ameliorate hyperpigmentary lesions.
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Experimental dermatology · Aug 2005
Stratum corneum hydration and flexibility are useful parameters to indicate clinical severity of congenital ichthyosis.
To determine any correlation between the stratum corneum barrier function and the phenotypic severity of congenital ichthyosis, we studied stratum corneum hydration, flexibility, thickness and transepidermal water loss (TEWL) in patients with congenital ichthyosis. Seven patients with congenital ichthyosis aged 2-46 years and age-matched controls were included in the present study. We divided seven patients into two groups; patients with non-bullous type (non-bullous congenital ichthyosiform erythroderma patients) and patients with the bullous type of congenital ichthyosis (bullous congenital ichthyosiform erythroderma and ichthyosis bullosa of Siemens). ⋯ A significant, positive correlation was also observed between the VAS score and stratum corneum thickness. There was a positive correlation between the VAS score and TEWL on both the extensor and flexor sides of the forearm and back. We conclude that stratum corneum hydration, flexibility and thickness measured by the corneometer, and TEWL on the arm may be a useful indicator of the severity of ichthyosis phenotype.
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Experimental dermatology · Jun 2005
Atopic dermatitis-like pruritic skin inflammation caused by feeding a special diet to HR-1 hairless mice.
Dry skin/barrier dysfunction is considered to be one of the characteristic features of atopic dermatitis (AD). When HR-1 hairless mice are fed a special diet, HR-AD, dry red skin is induced. We examined whether HR-AD-fed mouse could be used as a model for AD by showing itch-associated scratching behaviour and by analysing the immunological change. ⋯ The skin barrier dysfunction in HR-AD-fed mice is closely associated with the development of AD-like pruritus. Changes in the immunological parameters observed may be the consequence of skin barrier dysfunction. Our findings suggest that HR-AD-fed mouse could be used as a dry skin-based experimental model for AD.
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Experimental dermatology · Mar 2005
Inhibition of scratching behaviour caused by contact dermatitis in histidine decarboxylase gene knockout mice.
A neuronal system dedicated to itch consists of primary afferent and spinothalamic projection neurons. Histamine is thought to be one of the main mediators for the transmission of itch sensation. However, there are little available information on the role of histamine in scratching behaviour and sensory transmission of atopic dermatitis and chronic eczema. ⋯ The expression of c-Fos was specifically upregulated in HDC (+/+) mice in lamina I of the spinal dorsal horn following repeated DCP application. Scratching behaviour in chronic contact dermatitis in mice was thought mainly mediated with histamine. The afferent pathway of sensation in chronic contact dermatitis model may connect with the central nervous system through lamina I of the spinal dorsal horn.
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Experimental dermatology · Jul 2004
Measurement of cytokine expression and Langerhans cell migration in human skin following suction blister formation.
Contact allergen-induced migration of epidermal Langerhans cells (LCs) to draining lymph nodes is dependent upon receipt by LCs of at least two cytokine signals provided by tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta. It has been reported previously that intradermal injection of healthy human volunteers with homologous TNF-alpha or IL-1beta each induces a significant reduction in LC frequency, as measured in epidermal sheets prepared from 6-mm punch biopsies. In the current experiments, we have compared the frequency of LCs in punch biopsies with those obtained concurrently in epidermal sheets from the roofs of suction blisters isolated from the sun-protected buttock skin of healthy adult volunteers. ⋯ However, this technique provides an opportunity to profile induced changes in the cutaneous cytokine environment, with cytokine expression measured by a multiple cytokine array system. Using this technique, intradermal injection of IL-1beta was found to cause a marked upregulation of proinflammatory cytokines including TNF-alpha, IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1) and the anti-inflammatory cytokine IL-10 in fluid from suction blisters raised at the site of injection. In conclusion, the suction blister technique appears to be a powerful tool for measurement of induced changes in cutaneous cytokines.