Peter A. Philipsen

Vitamin D Production after UVB Exposure Depends on Baseline Vitamin D and Total Cholesterol but Not on Skin Pigmentation

UVB radiation increases serum vitamin D level expressed as 25-hydroxyvitamin-D(3) (25(OH)D), but the influence of skin pigmentation, baseline 25(OH)D level, and total cholesterol has not been well characterized. To determine the importance of skin pigmentation, baseline 25(OH)D level, and total cholesterol on 25(OH)D production after UVB exposure, 182 persons were screened for 25(OH)D level. A total of 50 participants with a wide range in baseline 25(OH)D levels were selected to define the importance of baseline 25(OH)D level. Of these, 28 non-sun worshippers with limited past sun exposure were used to investigate the influence of skin pigmentation and baseline total cholesterol. The participants had 24% of their skin exposed to UVB (3 standard erythema doses) four times every second or third day. Skin pigmentation and 25(OH)D levels were measured before and after the irradiations. Total cholesterol was measured at baseline. The increase in 25(OH)D level after UVB exposure was negatively correlated with baseline 25(OH)D level (P<0.001) and positively correlated with baseline total cholesterol level (P=0.005), but no significant correlations were found with constitutive or facultative skin pigmentation. In addition, we paired a dark-skinned group with a fair-skinned group according to baseline 25(OH)D levels and found no differences in 25(OH)D increase after identical UVB exposure.

Interdependence between body surface area and ultraviolet B dose in vitamin D production: a randomized controlled trial

Backgroundu2002 Ultraviolet (UV) B radiation increases serum vitamin D level expressed as 25‐hydroxyvitamin‐D3 [25(OH)D], but the relationship to body surface area and UVB dose needs investigation.

Vitamin D production depends on ultraviolet-B dose but not on dose rate: a randomized controlled trial.

Abstract:u2002 Ultraviolet‐B (UV‐B) radiation increases serum vitamin D level expressed as 25‐hydroxyvitamin D3 (25(OH)D), but the dose–response relationship and the importance of dose rate is unclear. Of 172 fair‐skinned persons screened for 25(OH)D, 55 with insufficient baseline 25(OH)Du2003≤u200350u2003nm (mean 31.2u2003nm) were selected and randomized to one of 11 groups of five participants. Each group was exposed to one of four different UV‐B doses: 0.375, 0.75, 1.5 or 3.0 standard erythema dose (SED) for 1, 5, 10 or 20u2003min. All participants had four UV‐B sessions with 2‐ to 3‐day interval with 24% of their skin exposed. Skin pigmentation and 25(OH)D were measured before and after the irradiations. The increase in 25(OH)D after UV‐B exposure (adjusted for baseline 25(OH)D) was positively correlated with the UV‐B dose (Pu2003=u20030.001; R2u2003=u20030.176) but not to dose rate (1–20u2003min). 25(OH)D increased in response to four UV‐B treatments of 3 SED with 24.8u2003nm on average and 14.2u2003nm after four UV‐B treatments of just 0.375 SED. In conclusion, the increase in 25(OH)D after UV‐B exposure depends on the dose but not on the dose rate (1–20u2003min). Further, a significant increase in 25(OH)D was achieved with a very low UV‐B dose.

A small suberythemal ultraviolet B dose every second week is sufficient to maintain summer vitamin D levels: a randomized controlled trial

Backgroundu2002 It is known that ultraviolet (UV) B radiation increases serum 25‐hydroxyvitamin D3 [25(OH)D] level. However, there is uncertainty about the relationship between the maintenance of vitamin D status and UVB.

Topical tacrolimus in combination with simulated solar radiation does not enhance photocarcinogenesis in hairless mice.

Abstract:u2002 Numerous studies have demonstrated the utility of topical tacrolimus ointment in atopic dermatitis. However, there is a concern that local immunosuppression by calcineurin inhibitors may enhance dermal photocarcinogenesis and carcinogenesis. Therefore, we investigated the influence of topical tacrolimus ointment on squamous cell carcinoma formation in hairless female C3.Cg/TifBomTac immunocompetent mice exposed to solar simulated radiation (SSR). In a first experiment, mice (nu2003=u2003200) had tacrolimus applied on their dorsal skin three times weekly followed by SSR (2, 4 or 6 standard erythema doses, SED) 3–4u2003h later. Tacrolimus did not reduce the time to tumor development and in the group receiving 4 SED it even had a protective effect (156u2003days vs 170u2003days, Pu2003=u20030.008). In a second experiment, mice (nu2003=u200350) were irradiated with 6 SED three times weekly for 3u2003months and subsequently treated five times weekly with topical tacrolimus to mimic the use of tacrolimus on sun‐damaged skin. The median time to the first skin tumor was 234u2003days in SSRu2003+u2003tacrolimus group compared with 227u2003days in the only SSR‐irradiated group (Pu2003=u20030.160). In a third experiment, mice (nu2003=u200325) had tacrolimus applied on their dorsal skin every day for 1u2003month, thereafter the group was irradiated with 4 SED three times weekly. The median time to the first skin tumor was 142u2003days in tacrolimusu2003+u2003SSR group compared with 156u2003days in the only SSR‐irradiated group from experiment 1 (Pu2003=u20030.363). We conclude that tacrolimus ointment does not accelerate photocarcinogenesis or induce any dermal carcinogenicity in hairless mice.

Topical pimecrolimus and tacrolimus do not accelerate photocarcinogenesis in hairless mice after UVA or simulated solar radiation.

Abstract:u2002 Pimecrolimus and tacrolimus are topical calcineurin inhibitors developed specifically for the treatment of atopic eczema. Experience with long‐term use of topical calcineurin inhibitors is limited and the risk of rare but serious adverse events remains a concern. We have previously demonstrated the absence of carcinogenic effect of tacrolimus alone and in combination with simulated solar radiation (SSR) on hairless mice. The aim of this study is to determine whether pimecrolimus accelerates photocarcinogenesis in combination with SSR or pimecrolimus and tacrolimus accelerate photocarcinogenesis in combination with UVA. We used 11 groups of 25 hairless female C3.Cg/TifBomTac immunocompetent mice (nu2003=u2003275). Pimecrolimus cream or tacrolimus ointment was applied on their dorsal skin three times weekly followed by SSR (2, 4, or 6 standard erythema doses, SED) or UVA (25u2003J/cm2) 3–4u2003h later. This was done up to 365u2003days in the SSR‐treated groups and up to 500u2003days in the UVA‐treated groups. Pimecrolimus did not accelerate the time for development of the first, second or third tumor in any of the groups. Median time to the first tumor was 240u2003days for the control‐2SED group compared with pimecrolimus‐2SED group (233u2003days), control‐4SED group (156u2003days) compared with pimecrolimus‐4SED group (163u2003days) and control‐6SED group (162u2003days) compared with pimecrolimus‐6SED group (170u2003days). Only one mouse in each of the three UVA groups developed a tumor. We conclude that pimecrolimus in combination with SSR and both pimecrolimus and tacrolimus in combination with UVA do not accelerate photocarcinogenesis in hairless mice.

Increase in serum 25-hydroxyvitamin-D3 in humans after solar exposure under natural conditions compared to artificial UVB exposure of hands and face

Vitamin D studies are often performed under controlled laboratory conditions and the findings may be difficult to translate to natural conditions. We aimed to determine and compare the doses of natural solar ultraviolet radiation (UVR) with doses of artificial UVB radiation of hands and face needed to increase serum 25-hydroxyvitamin-D(3) (25(OH)D). Furthermore, we aimed to investigate the natural course of 25(OH)D due to solar exposure from April to September. 46 Caucasian volunteers were included. 17 volunteers received solar UVR (Group 1) in their natural Danish environment. Individual daily solar UVR doses in standard erythema doses (SEDs) were determined with personal wristwatch UV-dosimeters. 29 volunteers (Group 2) received artificial UVB doses of 6 SEDs (N = 14) and 3 SEDs (N = 15) on hands and face during late-winter/early-spring when outdoor UVB is negligible. 25(OH)D-levels were determined around every second week during study periods. Solar-UVR doses and sun-exposure diaries with information of sun-exposed areas were available from 8 volunteers and used for comparison with artificial UVB doses. However no significant solar-induced Δ25(OH)D was observed when sun-exposed areas were limited to hands and face. Instead the earliest period (week 17-19) with significant Δ25(OH)D, occurring after a mean of 2 days of sun-exposing more than hands and face, was used to estimate an approximate UVR dose required to increase 25(OH)D. This estimate resulted in a dose of 4.1 solar SEDs required to increase 25(OH)D by 1 nmol l(-1). The artificial dose of 6 SEDs of only hands and face significantly increased 25(OH)D and resulted in a dose of 0.52 SEDs required to increase 25(OH)D significantly by 1 nmol l(-1). Artificial UVB was thus at least 8 times more efficient in increasing 25(OH)D than solar UVR at a UV-exposed area consisting of approximately hands and face. Solar UVR exposure of larger areas may lead to enhanced efficacy but was not relevant for this comparison. Significant solar-induced Δ25(OH)D was present earliest at April 8, maximal by early August and decreased by late August.

Photocarcinogenesis and toxicity of benzoyl peroxide in hairless mice after simulated solar radiation

Please cite this paper as: Photocarcinogenesis and toxicity of benzoyl peroxide in hairless mice after simulated solar radiation. Experimental Dermatology 2009;

Topical hydrocortisone, clobetasol propionate, and calcipotriol do not increase photocarcinogenesis induced by simulated solar irradiation in hairless mice

Please cite this paper as: Topical hydrocortisone, clobetasol propionate, and calcipotriol do not increase photocarcinogenesis induced by simulated solar irradiation in hairless mice. Experimental Dermatology 2010; 19: 973–979.

High death rate in mice treated topically with diclofenac

Abstract:u2002 Recently, 3% diclofenacnatrium gel (diclofenac) was introduced for the treatment of actinic keratoses. Data on photocarcinogenesis of topical diclofenac are limited, and we wished to investigate whether topical diclofenac can accelerate photocarcinogenesis using simulated solar radiation (SSR). Diclofenac was applied topically on the backs of hairless, female, C3.Cg/TifBomTac immunocompetent mice three times weekly followed by ultraviolet radiation (2, 3, or 4 Standard Erythema Dose) until death. There was a significant difference in survival between diclofenac‐treated groups and control groups (Pu2003<u20030.0001). Physical examination of the diclofenac‐treated mice showed peptic ulcers, oesophageal ulcers and gastrointestinal bleeding. To be sure that these side effects were not caused by topical absorption without oral ingestion, one group of mice was wearing Elizabethian collars and was single housed. Nevertheless, these mice also had gastrointestinal side effects. We terminated the experiment after 151u2003days when only a few mice remained in the diclofenac‐treated groups and most had symptoms of discomfort and weight loss. No tumors developed as a result of the early termination.