Genetic Variations in Cytokines and Cytokine Receptors Associated with Psoriasis Found by Genome-Wide Association

Genetic variants have long been suspected to be important in psoriasis. Recent work has suggested that HLA-Cw6 on chromosome 6 is the risk variant in the PSORS1 [MIM 177900] susceptibility locus that confers the greatest risk for early onset of psoriasis. Although numerous minor susceptibility loci have been identified by linkage analysis, few biologically relevant candidates have been discovered within these intervals. Recent large-scale genome-wide association studies have yielded new candidates in genes encoding cytokines with functional relevance to psoriasis. Polymorphisms within the genes encoding the IL-12 p40 subunit, IL12B, and one of the IL-23 receptor subunits, IL23R, have been replicated in US and European populations and overlap with risk of Crohn's disease. Polymorphisms within the gene encoding IL-13, a Th2 cytokine, also confer risk for psoriasis. Variants of the gene IL15 encoding IL-15 have been identified that associate with psoriasis in a Chinese population. These discoveries pose the challenge of elucidating the role of common genetic variants in susceptibility to and manifestations of psoriasis

Percutaneous Absorption Of Dexamethasone Estimated By A Plasma Radioimmunoassay

Percutaneous absorption of dexamethasone and its effect on the pituitary adrenal axis were measured in vivo in normal human subjects after application to skin. Specific plasma dexamethasone and cortisol radioimmunoassays were used. Following application of 1% dexamethasone on 500cm2 of normal skin, the plasma dexamethasone concentration was maximal at 2 hr, and the average absorption was 0.25% over 8hr; significant cortisol suppression occurred at 2, 4, and 8hr. This technique: (1) provides an accurate assessment of the in vivo absorption of dexamethasone applied to human skin, (2) avoids exposure of the subjects to radioactive steroids, (3) permits estimation of the quantity of unmetabolized steroids absorbed, and (4) serves as a possible model for the development of similar assays for other topical steroids

Cutaneous Blood Flow and Percutaneous Absorption: A Quantitative Analysis Using a Laser Doppler Velocimeter and a Blood Flow Meter

Cutaneous blood flow has been directly quantitated in vivo for the first time without animal death utilizing the rat skin sandwich flap. This was accomplished by conducting experiments that made a direct correlation between two instruments: a laser Doppler velocimeter and an electromagnetic blood flow meter. Data demonstrate that the correlation between these two instruments is high and reproducible (r = 0.96) with a small (1.3%) coefficient of variation. Blood flow to skin in the unmanipulated state varies from 0.7 to 1.2 mls/min in an anesthetized rat. Application of the blood flow correlation to the determination of percutaneous absorption of caffeine across human skin and benzoic acid across rat skin demonstrates that assuming cutaneous blood flow is a particular value day to day in any skin type results in an apparent wide range of total compound absorbed across that skin on independent occasions. Utilizing actual blood flow measurements to calculate the amount of chemical absorbed reduces the range of variability in the total amount of chemical absorbed and provides a more accurate knowledge of events occurring during a particular time of the absorption process. Quantitation of cutaneous blood flow will be useful in physiologic and pharmacologic studies where actual cutaneous blood flow is likely to be important to the processes studied, e.g., delivery of drug to skin, metabolism within the skin, and disposition of drug to blood and skin following topical drug application

Evaluation of Human Skin Reconstituted from Composite Grafts of Cultured Keratinocytes and Human Acellular Dermis Transplanted to Athymic Mice

This study evaluates the use of composite grafts of cultured human keratinocytes and de-epidermalized, acellular human dermis to close full-thickness wounds in athymic mice. Grafts were transplanted onto athymic mice and studied up to 8 wk. Graft take was excellent, with no instances of infection or graft loss. By 1 wk, the human keratinocytes had formed a stratified epidermis that was fused with mouse epithelium, and by 8 wk the grafts resembled human skin and could be freely moved over the mouse dorsum. Immunostaining for keratins 10 and 16 and for involucrin revealed an initial pattern of epithelial immaturity, which by 8 wk had normalized to that of mature unwounded epithelium. Mouse fibroblasts began to infiltrate the acellular dermis as early as 1 wk. By 8 wk fibroblasts had completely repopulated the dermis, and blood vessels were evident in the most superficial papillary projections, Dermal elements, such as rete ridges and elastin fibers, which were present in the starting dermis, persisted for the duration of the experiment. Grafts using keratinocytes from dark-skinned donors as opposed to light-skin donors had foci of pigmentation as early as 1 wk that progressed to homogenous pigmentation of the graft by 6 wk. These results indicate that melanocytes that persist in vitro are able to resume normal function in vivo. Our study demonstrates that composite grafts of cultured keratinocytes combined with acellular dermis are a useful approach for the closure of full-thickness wounds

Clinical Symptoms of Skin, Nails, and Joints Manifest Independently in Patients with Concomitant Psoriasis and Psoriatic Arthritis

This study correlated assessment tools for evaluating the severity of skin, nail, and joint symptoms in patients with psoriasis (Pso) and psoriatic arthritis (PsA). Adults with plaque Pso (with or without PsA) were enrolled from four U.S. institutions. Patients were evaluated using a novel 10-area Linear Psoriasis Area and Severity Index (XL-PASI), Psoriatic Arthritis Assessment (PsAA), Psoriatic Arthritis Screening and Evaluation Questionnaire (PASE), Nail Assessment (NA) and Joint Assessment (JA) tools, Psoriasis Weighted Extent and Severity Index (PWESI), and Lattice Physician Global Assessment (LS-PGA). Correlations between assessment tools and individual items in the assessment tools were performed. Data from 180 patients (55 with PsA) were analyzed. Highest correlations between tools (r = 0.77–0.88) were between the XL-PASI, PWESI and LS-PGA. Individual items in the XL-PASI correlated with items in the PWESI for extent skin symptoms, but not for all body areas. Overall, correlations were seen between hands and feet, between face and scalp, and between buttocks, chest, and back. Only low correlation was seen between items assessing joint symptoms with items assessing skin symptoms. These data support the notion that the complex phenotype of psoriatic disease requires instruments that assess the severity of skin, nails, and joints separately

DEVELOPMENT and ACCEPTABILITY of A NEW INTERNATIONAL QUALITY of LIFE INSTRUMENT SPECIFIC TO PHYSICAL APPEARANCE: BEAUTYQOL

Data Min Int, Geneva, SwitzerlandLab Sante Publ, Marseilles, FranceNatl Ctr Sci Res, Villeurbanne, FranceUniv Utah, Hlth Sci Ctr, Salt Lake City, UT USAUniversidade Federal de São Paulo, São Paulo, BrazilUniv Tokyo, Bunkyo Ku, Tokyo 113, JapanLOreal Int, Asnieres, FranceUniv Paris 06, Paris, FranceUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

The Effect of Hair Color on the Incorporation of Codeine into Human Hair

The influence of melanin on the binding of xenobiotics in hair will impact the interpretation of drug concentrations determined by hair testing. The purpose of this study was to determine if codeine, as a model compound of abused drugs, would be incorporated into black, brown, blond, or red hair as a function of melanin concentration. Such data would assist in the interpretation of codeine concentrations in hair and help elucidate the potential influence of hair color on incorporation of drugs. Male and female Caucasians with black (n = 6), brown (n = 12), blond (n = 8), or red hair (n = 6) and non-Caucasians with black hair (n = 12) aged 21-40 years were enrolled in the study. Each subject was administered oral codeine phosphate syrup in a dosage of 30 mg three times a day for five days. Twenty-four hours after the end of the treatment period, a 30-mg codeine dose was administered and the subject's plasma area under the concentration time curve (AUC) for codeine was determined. Codeine and melanin were measured in the first 3 cm of hair closest to the vertex region of the scalp prior to and 1, 4, 5, 6, and 7 weeks after dosing. The quantitative and qualitative melanin profiles were determined for each subjects hair to provide an objective measure of hair color. The plasma concentrations of codeine were measured to eliminate differences in the bioavailability and clearance of codeine as factors that might account for the differences in codeine hair concentrations. The subjects were asked not to cut their hair in the vertex region of the scalp or to use any form of chemical treatment on their hair, but otherwise normal hygienic measures were permitted. The mean (± SE) hair codeine concentrations 5 weeks after dosing were 1429 (± 249) pg/mg in black hair; 208 (± 17) pg/mg in brown hair; 99 (± 10) pg/mg in blond hair; and 69 (± 11) in red hair pg/mg. In black hair, codeine concentrations were 2564 (± 170) pg/mg for Asians and 865 (± 162) pg/mg for Caucasians. Similar concentration relationships were observed at weeks 4, 6, and 7. A strong relationship between the hair concentrations of codeine and melanin (R2 = 0.73) was observed. Normalization of the codeine concentration with the melanin concentration reduced the hair color differences observed. These data demonstrate that the interpretation and reporting of hair test results for codeine are influenced by hair color. After this dosing protocol, the proposed federal guideline cutoff of 200 pg/mg of codeine would result in 100% of subjects with black hair and 50% of subjects with brown hair being reported as positive, and subjects with blond or red hair would be reported as negative. The incorporation of these drugs into hair should be studied carefully in humans to ensure the appropriate interpretation of drug concentration

International development of the first quality of life instrument specific to cosmetology and physical appearance: the BeautyQol initiative

Data Mining Int, Geneva, SwitzerlandLab Sante Publ, Marseilles, FranceNatl Ctr Sci Res, Lyon, FranceUniversidade Federal de São Paulo, São Paulo, BrazilUniv Tokyo, Tokyo, JapanLoreal Int, Asnieres, FranceUniv Paris 06, Paris, FranceUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc