Non-invasive diffuse reflectance measurements of cutaneous melanin content can predict human sensitivity to ultraviolet radiation.

The diversity of human skin phenotypes and the ubiquitous exposure to ultraviolet radiation (UVR) underscore the need for a non-invasive tool to predict an individual's UVR sensitivity. We analysed correlations between UVR sensitivity, melanin content, diffuse reflectance spectroscopy (DR) and UVR-induced DNA damage in the skin of subjects from three racial/ethnic groups: Asian, black or African American and White. UVR sensitivity was determined by evaluating each subject's response to one minimal erythemal dose (MED) of UVR one day after the exposure. Melanin content was measured using DR and by densitometric analysis of Fontana-Masson staining (FM) in skin biopsies taken from unexposed areas. An individual's UVR sensitivity based on MED was highly correlated with melanin content measured by DR and by FM. Therefore, a predictive model for the non-invasive determination of UVR sensitivity using DR was developed. The MED precision was further improved when we took race/ethnicity into consideration. The use of DR serves as a tool for predicting UVR sensitivity in humans that should be invaluable for determining appropriate UVR doses for therapeutic, diagnostic and/or cosmetic devices.

Investigation of emtricitabine-associated skin pigmentation and safety in HIV-1-infected Japanese patients.

Emtricitabine (FTC) has been reported to cause skin pigmentation (SP), and the incidence of SP associated with FTC varied with ethnicity, with a higher rate in African-American patients (8%). We assessed the incidence of SP in Japanese HIV-1-infected patients receiving combination antiretroviral therapy (cART) with FTC for a period of 48 weeks and confirmed new findings of FTC-associated SP, including pathological characteristics. This was a multicenter, prospective, longitudinal non-randomized study. We evaluated the appearance of SP at 48 weeks as the primary endpoint in 155 Japanese patients, and secondary endpoints included the characteristics of the SP (location, color tone, size, and progression). Six cases (3.9%) of SP occurred at a median of 124 days (range: 7-259 days) within 48 weeks. The SP looked like an isolated dark spot, 1-2 mm in diameter, mainly on the hands and/or feet. The severity of all the SPs was mild. Each SP had disappeared or faded at a median of 112 days (range: 28-315 days) with continued FTC. FTC-associated SP was considered to be lentigo simplex by dermatoscopy and pathological appearance. In summary, the incidence of FTC-associated SP in Japanese patients was 3.9%, and was comparable to the previously reported incidence in Asian patients (4%). FTC-associated SP was not associated with any clinically significant symptoms and has little clinical significance.

Whitening efficacy of plant extracts including orchid extracts on Japanese female skin with melasma and lentigo senilis.

The purpose of this study was to assess the in vivo efficacy of a cosmetic formulation containing plant extracts including orchid extracts, compared to 3% vitamin C derivative formulated with the same excipient, in Japanese female adult volunteers with melasma and/or lentigo senilis. The ethics committee of Osaka National Hospital approved the protocol of the study. Before recruitment, selection and inclusion of a volunteer in this study, signed informed consent was obtained from each volunteer after she was given clear and precise information on the study, enabling her to appreciate the aim of the study and the consequences of her consent. Forty-eight female volunteers aged 30-60 years applied the plant extracts and vitamin C derivative to one side of the face. After repeated application for 8 weeks, efficacy was evaluated clinically by colorimetric measurements and subjectively using a questionnaire. After 8 weeks of treatment, both the clinical evaluations by a dermatologist and the questionnaire surveys by volunteers indicated that the cosmetic formulation containing plant extracts was significantly effective in improving the size, brightness, color intensity, clarity, visibility and global appearance of the pigmented spots, and also the luminosity complexion and skin clarity of the face. The good agreement between the results of clinical evaluations and those of questionnaire surveys showed that the orchid-rich plant extracts possess efficacy similar to vitamin C derivative in whitening the skin as well as melasma and lentigo senilis on the face of Japanese women.

Expression of estrogen receptor beta in normal skin, melanocytic nevi and malignant melanomas.

Sex hormones are known to be associated with increases of melanocytes and melanin production in human skin. However, the expression of estrogen receptor (ERalpha) in melanocytic lesions has been controversial. In 1996, a new subset of estrogen receptor was cloned, and named estrogen receptor beta (ERbeta). We used immunohistochemical staining to characterize the expression of ERalpha and ERbeta in normal skin and in melanocytic lesions. Normal sebaceous glands and hair follicles were positive for ERalpha and ERbeta. Other adnexal structures and constituents in the skin were positive for ERbeta, but not for ERalpha. Melanocytic nevi and malignant melanomas were negative for ERalpha, but both were positive for ERbeta. The ubiquitous expression of ERbeta may play a fundamental role in various normal skin cells and melanocytic tumors.

Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis.

Melanin plays an important role in protecting the skin against UV radiation, and melanomas and basal/squamous cell carcinomas occur more frequently in individuals with fair/light skin. We previously reported that levels of melanin correlate inversely with amounts of DNA damage induced by UV in normal human skin of different racial/ethnic groups. We have now separately examined DNA damage in the upper and lower epidermal layers in various types of skin before and after exposure to UV and have measured subsequent apoptosis and phosphorylation of p53. The results show that two major mechanisms underlie the increased photocarcinogenesis in fair/light skin. First, UV-induced DNA damage in the lower epidermis (including keratinocyte stem cells and melanocytes) is more effectively prevented in darker skin, suggesting that the pigmented epidermis is an efficient UV filter. Second, UV-induced apoptosis is significantly greater in darker skin, which suggests that UV-damaged cells may be removed more efficiently in pigmented epidermis. The combination of decreased DNA damage and more efficient removal of UV-damaged cells may play a critical role in the decreased photocarcinogenesis seen in individuals with darker skin.

Mechanisms of skin tanning in different racial/ethnic groups in response to ultraviolet radiation.

Ultraviolet radiation stimulates pigmentation in human skin, but the mechanism(s) whereby this increase in melanin production (commonly known as tanning) occurs is not well understood. Few studies have examined the molecular consequences of UV on human skin of various racial backgrounds in situ. We investigated the effects of UV on human skin of various races before and at different times after a single 1 minimal erythemal dose UV exposure. We measured the distribution of DNA damage that results, as well as the melanin content/distribution and the expression of various melanocyte-specific genes. The density of melanocytes at the epidermal:dermal junction in different types of human skin are remarkably similar and do not change significantly within 1 wk after UV exposure. The expression of melanocyte-specific proteins (including TYR (tyrosinase), TYRP1 (tyrosinase-related protein 1), DCT (tyrosinase-related protein 2), MART1 (melanoma antigens recognized by T-cells) gp100 (Pmel17/silver), and MITF (micropthalmia transcription factor)) increased from 0 to 7 d after UV exposure, but the melanin content of the skin increased only slightly. The most significant change, however, was a change in the distribution of melanin from the lower layer upwards to the middle layer of the skin, which was more dramatic in the darker skin. These results provide a basis for understanding the origin of different skin colors and responses to UV within different races.

Melkersson-Rosenthal syndrome caused by saprodontia: a case report.

A 24-year-old female patient with Melkersson-Rosenthal syndrome (MRS) in association with saprodontia is reported. She presented with lower labial swelling and left facial edema. Histological examination of the involved oral mucosa showed a noncaseating epithelioid granuloma. Results from the laboratory and imaging examinations were normal or negative. Her orofacial swelling disappeared after treatment of the saprodontia of the left first molar.

The inhibitory effect of androgen and sex-hormone-binding globulin on the intracellular cAMP level and tyrosinase activity of normal human melanocytes.

The effect of androgens on human melanocytes has not been well clarified. We studied the effects of androgens on normal human melanocytes in the presence or absence of sex-hormone-binding globulin (SHBG), which complexes with those hormones. Immunohistochemically, testosterone and SHBG co-localized on the cell membrane. Androgens such as testosterone, 5alpha-dihydrotestosterone, and methyltrienolone (R1881, a potent synthetic androgen), reduced intracellular cAMP levels after treatment with SHBG, but hydrocortisone had no effect. We also found that testosterone and R1881 slightly suppressed tyrosinase activity in melanocytes when treated with SHBG, although they had no effect on the expression of tyrosinase at the transcriptional or translational level, as measured by semi-quantitative reverse transcriptase-polymerase chain reaction and by Western blot analysis, respectively. Our results suggest that androgens may modulate tyrosinase activity at the posttranslational level through the cell membrane signaling pathway.

UV-induced DNA damage and melanin content in human skin differing in racial/ethnic origin.

DNA damage induced by UV radiation is a critical event in skin photocarcinogenesis. However, the role of racial/ethnic origin in determining individual UV sensitivity remains unclear. In this study, we examined the relationships between melanin content and DNA damage induced by UV exposure in situ in normal human skin of different racial/ethnic groups, phototypes, and UV sensitivities. The minimal erythema dose (MED) was established for each subject exposed to UVA/UVB radiation, and skin was biopsied before as well as 7 min, 1 day, and 1 wk after UV exposure. There was great variation among individuals in the amount of DNA damage incurred and rates of its removal. The results show that after exposure to 1 MED of UV, the skin of subjects from all groups suffered significant DNA damage, and that increasing content of constitutive melanin inversely correlated with the amount of DNA damage. It is clear from these results that measured erythemal UV sensitivity of the skin (MED) is a more useful predictor of DNA photodamage than is racial/ethnic origin or skin phototype and that rates of DNA damage removal following UV radiation may be the critical determinant of the UV sensitivity (including predisposition to cancer) of the skin.