A theoretical and experimental study of the temporal reduction in UV protection provided by a facial day cream.

OBJECTIVE: To investigate how the UV protection provided by a facial day cream reduces over the course of a day. METHODS: We developed a theoretical model using a Monte Carlo random sampling approach to estimate the variation in local thickness, and hence local effective SPF, at several different sites over the face. The input variables, which are labelled SPF, average application thickness, homogeneity of the product on the skin and the ability of the product to bind to the skin, allow examination of how these different factors affect the delivered photoprotection. We compared the results of our modelling with experimental determination of the binding of an oil-in-water moisturizing day cream with a rated SPF of 15 at various times over the course of a day by means of UV photography and digital image analysis. RESULTS: We demonstrated good agreement between our theoretical predictions of the temporal reduction in product thickness and the experimental observations. We used our modelling approach to show that a substantial reduction in lifetime UV burden on the face could be achieved by a daycare product delivering 3-fold (or greater) protection over the face. CONCLUSION: Comparison with experimental data confirmed the robustness and validity of our model, which predicts that products intended for daily use need to be formulated carefully and applied uniformly, and to have a half-life of binding to the skin of several hours. Products that bind less well to the skin, or are applied non-uniformly, are likely to be providing inadequate protection with regards to influencing the rate of photoaging of the skin. Our data suggest that after a single, realistic application of a day cream rated SPF15, consumers' faces remain protected to at least an average of 5-fold around the middle of the day, especially pertinent to indoor workers who are likely to be exposed to maximum UV levels as they venture outside during their lunch break.

Optimizing the spectral absorption profile of sunscreens.

OBJECTIVE: To investigate whether sunscreens provide optimal protection by exhibiting a uniform spectral absorption profile throughout the ultraviolet spectrum or by having a spectral profile in which absorption in the UVB waveband is greater than in the UVA region. METHODS: A sunscreen with a flat spectral absorption profile was compared with one of the same SPF in which the SPF to UVA protection was in the ratio of 3 : 1 in terms of protecting against erythema and chronic effects with different action spectra, as well as the total UV burden to the skin. RESULTS: A sunscreen with spectral profile in which absorption in the UVB waveband is greater than in the UVA region confers no benefit in terms of erythema (and endpoints with similar action spectra) than a sunscreen with the same SPF that exhibits uniform absorption at all wavelengths throughout the UV spectrum. More importantly, the '3 : 1 profile' offers inferior protection when endpoints with other action spectra are considered, as well as resulting in a total UV burden to the skin that is about 5 times higher than sunscreen products showing a flat spectral absorption profile. CONCLUSION: It may be tempting to believe that it is beneficial to increase the absorption of sunscreens in the UVB region relative to the UVA to reflect the fact that skin damage is associated more with UVB than UVA exposure. However, this belief is a fallacy and consumers are best served with sunscreens in which the spectral protection profile is uniform at all wavelengths throughout the UV spectrum.

The risk of squamous cell carcinoma in women from exposure to UVA lamps used in cosmetic nail treatment.

BACKGROUND: The use of ultraviolet (UV)A lamps for curing gel nails is widespread in the cosmetic nail industry. A report that two women who had undergone this treatment subsequently developed squamous cell carcinoma (SCC) on the dorsum of hands has prompted some concern about the safety of this procedure. OBJECTIVES: To estimate the number of women who would need to be exposed to UVA nail lamps for one woman to develop SCC on the dorsum of hands, who would not have done so otherwise. METHODS: A mathematical model that combines age and UV exposure was used to compare the risk of developing SCC due to typical sun exposure with the risk of inducing these cancers from exposure to UVA nail lamps. RESULTS: For typical usage, the analysis indicates that tens or hundreds of thousands of women would need to use a UVA nail lamp regularly for one to go on to develop SCC on the dorsum of the hands as a direct consequence. CONCLUSIONS: The risk of inducing an SCC from exposure to UVA nail lamps is very low and one that is likely to be accepted by most women. Even then, the risk can be reduced to virtually zero by wearing fingerless gloves when the hands are being exposed.

An overview analysis of the time people spend outdoors.

BACKGROUND: An important factor in determining our exposure to sunlight, and the consequent impact on skin health and vitamin D status, is the time we spend outdoors. OBJECTIVES: To determine estimates of the typical times per day spent outdoors during weekdays, weekends and holidays during a summer season. METHODS: A number of published studies giving data on the time per day spent outdoors by people were reviewed and a meta-analysis performed. From these data summary estimates of the average time per day outdoors were extracted. RESULTS: Time spent per day outdoors during weekdays and weekends is positively skewed, with a normal distribution of times outdoors during holidays. The median times per day outdoors during weekdays and weekends gave pooled estimates of 1·04 and 1·64 h, respectively. Corresponding values for the pooled estimates of mean times outdoors during these two periods were 1·43 and 2·38 h. The mean time per day outdoors during holiday exposure is 5-6 h. CONCLUSIONS: Summer-long distribution of times spent outdoors on a daily basis exhibits a highly skewed nature that highlights the difference between our adventitious and recreational exposure. Over the course of a summer season, when people are outside, they spend on average of 1-2 h per day outdoors.

Modelling the seasonal variation of vitamin D due to sun exposure.

BACKGROUND: The current interest in vitamin D as a preventive agent in many chronic diseases has led to a reappraisal of adequate sun exposure. Yet just what constitutes adequacy remains to be clearly defined and validated. To do this requires an understanding of how behaviour outdoors during the year translates into seasonal changes in vitamin D status. OBJECTIVES: To develop a model for estimating the changes in serum 25-hydroxyvitamin D [25(OH)D] levels as a consequence of sun exposure throughout the year. METHODS: A novel mathematical model is described that incorporates the changes in serum 25(OH)D following a single, whole-body exposure to solar ultraviolet radiation with daily sun exposure in order to estimate the annual variation in serum 25(OH)D. RESULTS: The model yields results that agree closely with measured data from a large population-based study. Application of the model showed that current advice about 10-20 min of daily sun exposure during the summer months does little in the way of boosting overall 25(OH)D levels, while sufficient sun exposure that could achieve a worthwhile benefit would compromise skin health. CONCLUSIONS: There is little in the way of public health advice concerning the benefits of sun exposure that can be given as an effective means of maintaining adequate vitamin D levels throughout the year. Instead it would seem safer and more effective to fortify more foods with vitamin D and/or to consider the use of supplements during the winter months. Messages concerning sun exposure should remain focused on the detrimental effects of excessive sun exposure and should avoid giving specific advice on what might be 'optimal' sun exposure.

NFAT regulates induction of COX-2 and apoptosis of keratinocytes in response to ultraviolet radiation exposure.

The nuclear factor of activated T cells (NFAT) transcription factors are regulated by calcium/calcineurin signals and play important roles in T cells, muscle, bone, and neural tissue. NFAT is expressed in the epidermis, and although recent data suggest that NFAT is involved in the skin's responses to ultraviolet radiation (UVR), the wavelengths of radiation that activate NFAT and the biological function of UV-activated NFAT remain undefined. We demonstrate that NFAT transcriptional activity is preferentially induced by UVB wavelengths in keratinocytes. The derived action spectrum for NFAT activation indicates that NFAT transcriptional activity is inversely associated with wavelength. UVR also evoked NFAT2 nuclear translocation in a parallel wavelength-dependent fashion and both transcriptional activation and nuclear translocation were inhibited by the calcineurin inhibitor cyclosporin A. UVR also evoked NFAT2 nuclear translocation in three-dimensional skin equivalents. Evidence suggests that COX-2 contributes to UV-induced carcinogenesis. Inhibiting UV-induced NFAT activation in keratinocytes, reduced COX-2 protein induction, and increased UV-induced apoptosis. COX-2 luciferase reporters lacking functional NFAT binding sites were less responsive to UVR, highlighting that NFAT is required for UV-induced COX-2 induction. Taken together, these data suggest that the proinflammatory, antiapoptotic, and procarcinogenic functions of UV-activated COX-2 may be mediated, in part, by upstream NFAT signaling.

Sunscreens as a preventative measure in melanoma: an evidence-based approach or the precautionary principle?

BACKGROUND: Meta-analyses of observational case-control studies have demonstrated no association between sunscreen use and the development of malignant melanoma. OBJECTIVES: To postulate whether modern sunscreens are likely to be effective as a preventative agent in melanoma and, if so, how many cases might be avoided by their use. METHODS: The potential number of melanomas prevented by encouraging the use of modern, high SPF, broad spectrum sunscreens during recreational summer exposure was estimated by combining the prevalence of their use with the relative risk of melanoma in nonusers compared with those people who regularly use these products. RESULTS: Notwithstanding the inherent uncertainties and assumptions that this approach involves, it is shown that significant numbers of melanomas might be avoided by regular sunscreen use during recreational summer sun exposure, and with them appreciable financial, social and emotional costs, even for very modest estimates of the benefit of broad-spectrum sunscreens. CONCLUSIONS: Despite the lack of evidence demonstrating the efficacy of modern sunscreens in preventing melanoma, it is argued that it would be irresponsible not to encourage their use, along with other sun protection strategies, as a means of combating the year-on-year rise in melanoma incidence.

Reported sun exposure, attitudes to sun protection and perceptions of skin cancer risk: a survey of visitors to Cancer Research UK's SunSmart campaign website.

BACKGROUND: Skin cancer is the most commonly diagnosed cancer in the U.K. With the aim of reducing, and hopefully reversing, the year-on-year rise in skin cancer incidence, SunSmart, the U.K.'s national skin cancer prevention campaign, has been hosted by Cancer Research UK since 2003. OBJECTIVES: To gather data about how much time visitors to the SunSmart website spend in the sun, their preferred forms of sun protection and their use of tools such as sun-reactive skin type and ultraviolet (UV) index. METHODS: The study was carried out using a quantitative on-line survey hosted by Cancer Research UK's SunSmart website (http://www.sunsmart.org.uk) between May and September 2007. RESULTS: Just over 2000 respondents completed the survey. Young adults are more likely to experience sunburn than older adults, a factor that was found to be much more important than individual susceptibility to sunburn. Initiatives such as using the UV index to guide sun exposure and checking skin regularly for unusual changes both appeared to be associated with a lower incidence of recent sunburn. The distribution of time spent outdoors by indoor workers during summer months demonstrated clearly how important recreational exposure is in influencing the overall solar UV burden. CONCLUSIONS: This on-line survey, while not entirely representative of the U.K. population, has highlighted those factors that can be effective in reducing the incidence of sunburn, and presumably skin cancer, and that messages about the secondary prevention of skin cancer clearly have some overlap with those advocating primary prevention.

The influence of HIV infection on the age dependence of squamous cell carcinoma of the skin in South Africa.

BACKGROUND: Cancer incidence typically increases with age, but it is not known whether ethnic characteristics influence the age dependence of squamous cell carcinoma of the skin (SCC). OBJECTIVES: (i) To determine the age dependence of SCC in the black African, coloured and white population groups of South Africa (SA); and (ii) to show whether any differences in the rate of change of age dependence could be influenced by diversity in behaviour and lifestyle, especially with regard to the prevalence of HIV infection, rather than by a fundamental variation in cancer biology between the populations. METHODS: Linear regression analysis was applied to the logarithm of the age-specific incidence rates for SCC v. the logarithm of age between 35 and 74 years. The slopes of the regression (age exponent) were compared for each subset of gender, population group and year of diagnosis (between 2000 and 2010). RESULTS: The most notable feature was the low value of the age exponent in both male and female black African compared with the white and coloured populations. This finding could be explained in part by the difference in the prevalence of HIV infection in the black African population group compared with the white and coloured population groups. CONCLUSIONS: The prevalence of HIV infection in black Africans in SA tends to decrease the apparent age component in SCC compared with the white and coloured population groups. Other factors relating to lifestyle and behaviour that differ between the population groups are also likely to influence the age component in SCC.

Hypersensitivity of human lymphocytes to UV-B and solar irradiation.

T-lymphocytes from three normal human donors, irradiated with broad-spectrum UV-B (peak emission, 312 nm), are 20-fold more sensitive than fibroblasts from four normal donors in a clonogenic assay. We have compared the formation of thymine cyclobutane dimers and pyrimidine-(6-4)-pyrimidone photoproducts following irradiation by UV-C (254 nm) and UV-B and studied killing at doses giving equal dimer formation. UV-B killing of fibroblasts appears to be associated with dipyrimidine photoproduct formation, whereas UV-B killing of lymphocytes is mediated by nondimer damage. Strand breakage following UV-B irradiation measured using the "Comet" assay (single cell gel electrophoresis) reflects this nondimer damage and has kinetics consistent with excisable damage. Lymphocytes from three excision-deficient xeroderma pigmentosum donors show reduced strand breakage and increased killing following UV-B irradiation, compared with lymphocytes from normal donors. We therefore suggest that UV-B kills human lymphocytes by excisable nondimer damage and that xeroderma pigmentosum lymphocytes are defective in its repair. The putative nondimer damage does not appear to be associated with radical attack, and the strand breakage is not a manifestation of apoptosis. A 1-min exposure of human lymphocytes in vitro to natural sunlight is sufficient to produce damage measurable by the Comet assay.

A quantitative study of the effect of terfenadine on cutaneous erythema induced by UVB and UVC radiation.

Terfenadine, given in sufficient dose to cause maximum H1 receptor blockade, had no effect on the intensity of UVB or UVC erythema measured with a reflectance instrument at 4, 8, and 24 h after irradiation. Histamine, acting on the H1 receptor, is not a significant mediator of UVB or UVC erythema.

The time course of UVB and UVC erythema.

The time course of ultraviolet erythema was measured using six different exposure doses of UVC and UVB radiation in each of eight adult subjects. The intensity of erythema was measured by reflectance spectrophotometry at 4, 8, 24, 36, and 48 h after irradiation. In five subjects there was no significant difference between the form of the UVB and UVC erythema time-course. In three subjects a significant difference was observed, but this was random rather than systematic between subjects. The results do not confirm the previously reported major differences in time course between the two qualities of radiation.

The 99mTc-DTPA dynamic renal scan with deconvolution analysis.

Dynamic renal studies were performed with 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). The results were analyzed by the method of mathematical deconvolution in order to obtain the impulse response function of the kidney. Regional analysis of the kidney was attempted by evaluating the independent responses of the renal parenchyma and renal pelvis to a bolus injection of 99mTc-DTPA.

Phototoxic potential of thiazide diuretics in normal subjects.

Monochromator phototesting has been carried out in 22 subjects before and 2 weeks after therapy with either bendroflumethiazide (bendrofluazide) or hydrochlorothiazide. An increase in erythemal sensitivity was observed in several subjects in those wave bands that are maximally absorbed by the respective drugs in vitro. Both drugs showed similar phototoxic capabilities, yet in clinical practice, reports of photosensitivity caused by hydrochlorothiazide are much more common than those caused by bendroflumethiazide. One possible reason is suggested.

A comparison of the dose-response relationship for psoralen-UVA erythema and UVB erythema.

Twenty patients with psoriasis were phototested to determine their erythemal responses to UVB and psoralen-UVA (PUVA) (oral 8-methoxypsoralen). The smallest ultraviolet radiation doses to produce erythema (minimal erythema dose and minimal phototoxic dose, respectively) were recorded and dose-response curves were constructed for UVB (24 hours after irradiation) and PUVA (48 hours) using objective measurement. The choice of a 48-hour measurement was validated by phototesting an additional 11 subjects to determine the time course of PUVA erythema. No correlation was demonstrated between minimal erythema dose for UVB, minimal phototoxic dose for PUVA, and sun-reactive skin type. The mean slope of the dose-response curve for UVB erythema was four times steeper than that for PUVA. Psoralen-UVA erythema reached a broad maximum between 48 and 96 hours after irradiation. Using objective methods we have demonstrated that the commonly accepted view of a steep dose-response relationship for PUVA erythema is not valid.

PUVA-induced blisters, complement deposition, and damage to the dermoepidermal junction.

We followed the course of 56 patients receiving psoralen plus long-wave ultraviolet light (PUVA) therapy. Nonhemorrhagic blisters developed on clinically normal skin on the limbs of seven patients. Seeming to be related to friction and trauma, the blisters form as a result of damage to the basal and suprabasal layers. Perilesional skin specimens from all blistered patients contained granular deposits of C3 at the dermoepidermal junction, around the upper dermal blood vessels, or at both sites. The average time for initiation and complete formation of suction blisters was measured in 51 patients at different stages during the course of PUVA treatment. Blister separation was in the lamina lucida, with the pemphigoid antigen in the roof while the blister floor contained the lamina densa, laminin, and type IV collagen. This impaired dermoepidermal adhesion was a general phenomenon that occurred in all PUVA-treated patients. The mechanism remains to be determined.

A comparison of dosimeters used for solar ultraviolet radiometry.

Radiometric measurements of terrestrial sunlight using three different types of broad-band dosimeters were compared with equivalent integrated quantities obtained from simultaneous spectroradiometric measurements. Measurements were made at Durham, UK (55 degrees N) during one day in mid-summer and one day in the autumn. By this means it was possible to encompass a wide range of ultraviolet irradiances. There was close agreement between UV-A irradiance measured using a broad-band radiometer and determined spectroradiometrically over the whole range of irradiances when allowance was made for the spectral sensitivity of the UV-A radiometer. The agreement between erythemally-effective irradiance determined spectroradiometrically and the response of a Robertson-Berger meter showed some non-linearity due to the mismatch between the erythema action spectrum and spectral response of the sensor. There was a similar disparity in agreement between erythemally-effective dose determined spectroradiometrically and the response of polysulphone film for similar reasons. Nevertheless it is concluded that if these latter two dosimeters are calibrated using sunlight, or a solar simulator, as the source, they can yield data which are sufficiently reliable for many applications.