In vitro model of vitamin D3 (cholecalciferol) synthesis by UV radiation: dose-response relationships

Vitamin D deficiency is a major health concern worldwide. Very little is understood regarding its production in the human body by exposure to UV radiation. In particular, we have no means of predicting how much vitamin D (cholecalciferol) will be produced in the skin after exposure to sunlight. Using a refined in vitro model, we found that there is a nonlinear relationship between UV dose and cholecalciferol synthesis. Two minimal erythemal doses (MED) of UV radiation produced 1.84 microg/mL of cholecalciferol whereas 4 MED produced 2.81 microg/mL. We also found that the production of cholecalciferol is restricted by the initial concentration of its precursor (7-dehydrocholesterol, 7-DHC). For example, using an initial concentration of 7-DHC of 102 microg/mL, the resultant cholecalciferol production was 1.05 microg/mL after receiving 4 MED exposure. Under the same exposure conditions, an initial concentration of 305 microg/mL yielded 2.81 g/mL of cholecalciferol. The data presented in this paper has important implications for humans, including: (1) increasing UV exposure does not result in a proportionate increase in the amount of cholecalciferol that is produced; and (2) the initial concentration of 7-DHC in the skin may impact the amount of cholecalciferol that can be synthesized. When translating these results to population groups, we will discuss how the sun exposure message needs to be carefully formulated to account for such considerations.     

Spectral monitoring of biologically active solar UVB radiation using an in vitro model of vitamin D synthesis

Vitamin D synthetic capacity of sunlight is the most well known beneficial effect of solar UV radiation. The article describes the new method of biological dosimetry of solar (and artificial) UV radiation based on an in vitro model of vitamin D synthesis (D-dosimeter). Particular attention is given to spectrophotometric analysis of the multicomponent mixture of vitamin D photoisomers that has been developed for the most effective use of D-dosimeter in situ.     

Sunbed radiation provokes cutaneous vitamin D synthesis in humans--a randomized controlled trial

We wanted to investigate whether the use of sunbeds with sunlamps emitting mainly UVA and only 0.5% or 1.4% UVB will increase the level of serum 25-hydroxyvitamin D (25(OH)D). In a randomized, controlled, open study on healthy, Caucasian females (> 50 years) sunbed radiation was given as follows: four 6-min sunbed sessions (days 0, 2, 4 and 7) and four 12-min sunbed sessions (days 9, 11, 14 and 16 ) with sunlamps emitting 0.5% UVB (n = 20) or with sunlamps emitting 1.4% UVB (n = 15). The controls (n = 21) had no intervention. Serum levels of 25(OH)D were measured on days 0, 9 and 18 in all three groups. The average increase in serum 25(OH)D from day 0 to day 9 was 12 nmol L(-1) (SD 11 nmol L(-1), P = 0.0002) in the 0.5% UVB group and 27 nmol L(-1) (SD 9 nmol L(-1), P < 0.0001) in the 1.4% UVB group. From day 9 to day 18 a further but not significant increase in serum 25(OH)D of 3 nmol L(-1) (SD 9 nmol L(-1), P = 0.2) in the 0.5% UVB group and 0.6 nmol L(-1) (SD 18 nmol L(-1), P = 0.9) in the 1.4% UVB group was seen. No significant changes were found in the control group. Increasing with UVB dose and exposure time, 37-64% of the sunbed sessions resulted in side effects such as erythema or polymorphic light eruption. The results showed that sunbeds emitting 0.5% and 1.4% UVB increased 25(OH)D serum levels. The increases were dose dependent but reached a plateau after few sessions. Sunbed use as vitamin D source is, however, not generally recommendable due to the well-known carcinogenicity and high frequency of acute side effects.     

A mathematical model for seasonal variability of vitamin D due to solar radiation

It is widely recognized that vitamin D deficiency has detrimental health consequences. The ultraviolet (UV) B radiation increases the serum vitamin D level, expressed by 25-hydroxyvitamin-D(3) [25(OH)D]. An analytical model is presented to calculate the serum 25(OH)D changes throughout a year, caused by the solar exposure variability due to geophysical and habitual factors. The model is tuned by taking into account recent experimental results of serum 25(OH)D changes, after a series of artificial (by fluorescent tubes) UV exposures. The model uses the erythemal and vitamin D weighted irradiances, inferred from the Brewer spectrophotometer and the Kipp and Zonen broad-band meter measurements, carried out in Belsk (52°N, 21°E), Poland, in 2010. The modeled seasonal pattern of the serum 25(OH)D concentration in Polish indoor workers is only slightly different, than in subjects with typical outdoor activity habits, and in those with sun-seeking behavior. A deep minimum in the serum 25(OH)D concentration appears in late winter, regardless of outdoor activity habits. An extra sunbathing to boost the vitamin D level is not worth taking, because of a minor improvement of the vitamin D status, and because of a greater erythema risk. It would be much safer and more effective to maintain an adequate vitamin D level through diet supplements, even in summer, for non sun-seeking subjects.     

Conformational analysis of model compounds of vitamin D by theoretical calculations

A conformational analysis of two model compounds of vitamin D was carried out by means of theoretical computations, Ab initio calculations were carried out using the standard 6-31G* basis set at the Hartree–Fock (HF) level of theory. In addition, the Møller–Plesset (MP2) correlation treatment was applied on the simplest model. Semiempirical calculations were also performed using the AM1 Hamiltonian. The results predict stable A-ring twist forms with energies in the order of 4–6 kcal/mol relative to the global minimum, significantly higher than those reported from molecular mechanics calculations. In addition, a folded conformation was found by the HF optimizations; however, its stability is predicted to be very poor. Comparison of the theoretical results with experimental data is discussed. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1647–1655, 1997     

Stereoselective synthesis of CD-ring precursors of vitamin D derivatives

Two expedious and useful approaches to the construction of Vitamin D trans-hydrindane building blocks are proposed. These involve the desymmetrization of the anti meso-acetylmethyldivinylcyclopentane 3 which proceeds through either the selective formation of epoxyketone 5 and intramolecular enolate cyclisation or a xanthate groupe transfer mediated radical cyclization to furnish trans-hydrindanes 7 and 16 respectively. Epoxyketone 5 is prepared by means of a three-step reaction process including reduction of the ketone moiety, bishomoallylic alcohol-directed epoxidation and Dess-Martin oxidation. Alternatively, an asymmetric reduction using borane/tetrahydrofuran complex and (R)-2-methyl-CBS-oxazaborolidin made accessible the epoxyketone in good optical purity. The xanthate 16 can undergo a Johnson sulfoximine ketone resolution that allows access to both enantiomers. Various derivatizations of 16 to more elaborated synthetic intermediates are also reported.     

Degradation of ROMP-based bio-renewable polymers by UV radiation

The degradation of a bio-renewable polymer under UV exposure was studied using various methods. Degradation of the bio-renewable polymer increased with increasing exposure time. Enhanced cross-link density in the early stage of degradation was confirmed by Soxhlet extraction. Tensile testing showed a transition from ductile failure to brittle fracture. Surface cracks and embrittlement were primary reasons for most reductions in mechanical properties, such as tensile strength and breaking strain. The effects of degradation were confined to the surface of thick bio-based polymer specimens, confirmed by both SEM and PAS-FTIR. Depth profile studies of degraded samples showed that the concentration of oxidation products, such as hydroxyl and carbonyl groups, varied with depth depending on the diffusion of oxygen.     

Continuous-flow synthesis of activated vitamin D3 and its analogues

An efficient, two-stage, continuous-flow synthesis of 1α,25-(OH)(2)-vitamin D(3) (activated vitamin D(3)) and its analogues was achieved. The developed method afforded the desired products in satisfactory yields using a high-intensity and economical light source, i.e., a high-pressure mercury lamp. In addition, our method required neither intermediate purification nor high-dilution conditions.     

Solar radiation, vitamin D and survival rate of colon cancer in Norway

Solar radiation contributes significantly to the status of serum calcidiol (25-hydroxyvitamin D3, 25-(OH)D3) in humans, even at the high latitudes of northern Norway. Thus, in late summer the serum concentration of calcidiol is roughly 50% larger than that in late winter, when the solar radiation in Norway contains too little ultraviolet radiation to induce any synthesis of vitamin D3 in human skin. This seems to influence the prognosis of colon cancer. We here report that the survival rate of colon cancer in men and women, assessed 18 months after diagnosis, is dependent on the season of diagnosis. A high serum concentration of calcidiol at the time of diagnosis, i.e. at the start of conventional therapy, seems to give an increased survival rate. This agrees with cell and animal experiments reported in the literature, as well as with epidemiological data from some countries relating colon cancer survival with latitude and vitamin D3 synthesis in skin. One possible interpretation of the present data is that, the level of calcidiol, or its derivative calcitriol (1alpha,25-dihydroxyvitamin D3, 1alpha,25-(OH)2D3), may act positively in concert with conventional therapies of colon cancer.     

Determination of vitamin D2 in emulsified nutritional supplements by solid-phase extraction and column-switching high-performance liquid chromatography with UV detection

This paper deals with a method for solid-phase extraction of trace amounts of vitamin D2 (VD2, 19 ng/g) from emulsified nutritional supplements, which contain 50 kinds of compounds, followed by column-switching high-performance liquid chromatography (HPLC) with UV detection at 265 nm. VD2 is present at 1000-20,000,000 times lower concentration than other components. Bond Elut C18 cartridge was chosen as for the emulsified nutritional supplements after comparison with eight other types. A sample solution was applied to the solid-phase extraction cartridge and VD2 was eluted by methanol followed by HPLC. The effects of sample pH, eluent composition and eluate volume on the retention and elution of VD2 on Bond Elut C18 cartridge were examined. The resulting method was simple, rapid (analysis time: approximately 20 min), sensitive (detection limit: approximately 0.1 ng per injection (200 microl) at a signal-to-noise ratio 3:1), and reproducible (relative standard deviation: approximately 6.2%, n=5). The calibration graph for VD2 was linear in the range of 0.1-3 ng per injection (200 microl). Recovery of VD2 was approximately 80% by the standard addition method.     

Photo-degradation of PADC by UV radiation at various wavelengths

The effects of ultraviolet (UV) photons at different wavelengths (namely UVA, UVA + B and UVC) on PADC (polyallyl diglycol carbonate) were investigated in this study. The chemical modifications were studied by Fourier Transform Infrared (FTIR) spectrometry and the corresponding nano-mechanical properties were also determined. The scission process could be revealed by the decreasing net absorbance at particular wavelengths in the infrared (IR) spectra. On the other hand, the cross-linking was indicated by the increased hardness and reduced modulus determined with a nanoindenter. UVA caused no chemical modifications as most of the UV photons in this range were not absorbed by PADC. Both UVA + B and UVC irradiation caused scission of the chemical bonds, which was also manifested by the faster chemical etching rates. The bulk etch rate increased from 1.37 to 5.73 μm/h for 60 h of UVA + B exposure for 3 h of chemical etching, and increased to 5.13 μm/h for 60 h of UVC exposure. For 3 h of etching, the bulk etch rate remained unchanged for UVC exposures longer than 20 h. The saturation of the bulk etch rate was due to formation of cross-linked structures on the surface of the PADC samples. It was also observed that a UVC exposure caused a comparatively higher bulk etch rate at the beginning of etching. However, the bulk etch rate decreased with the depth of the PADC sample due to the lower rate of oxygen diffusion into deeper regions.     

An enantioselective synthesis of the A-ring synthon for vitamin D3 metabolites by chemicoenzymatic approach

The A-ring synthon for vitamin D3 metabolites having 1α hydroxyl group is synthesized starting from a chiral monoester 6 enzymatically generated.     

Palladium-catalyzed synthesis of dienynes related to vitamin D from enol triflates

This note describes a simple synthesis of Lythgoe-type dienynes based on palladium catalyzed coupling of kinetic Grundmann's ketone enol triflate and acetylenic compounds containing the vitamin D A-ring fragment.     

Study of UV radiation dose received by the Spanish population

Excess exposure to UV radiation can affect our health by causing sunburn, skin cancer, etc. It is therefore useful to determine the UV dosage received by people as a way of protecting them from the possible negative effects that this kind of radiation can cause. In this work, the personal outdoor percentage, which shows the time spent in outdoor activities, as well as personal UV doses, has been calculated by means of global UV radiation on a horizontal plane. A database of average daily UVB radiation on the horizontal plane given by the National Institute of Meteorology has been used. In this work we evaluate the standard erythema dose of the Spanish population throughout the year.     

Ultraviolet radiation, vitamin D and risk of prostate cancer and other diseases

Most common diseases appear to result from complex, poorly understood interactions between genetic and environmental factors. Relatively few factors have been unequivocally linked with disease risk or outcome. Evidence from various studies using different experimental approaches has been interpreted as showing that, apart from its harmful effects on the pathogenesis of the common skin cancers, ultraviolet radiation (UVR) may exert a beneficial effect on development of various internal cancers and other pathologies. This concept is supported by parallel studies showing that hypovitaminosis D is linked with increased risk of various diseases including insulin resistance and multiple sclerosis. These findings suggest that, first, host factors such as skin pigmentation that affect UVR-induced synthesis of vitamin D and, second, polymorphism in genes that mediate the effectiveness of vitamin D action are susceptibility candidates for a variety of diseases. Collectively, these data suggest the hypothesis that, via effects on vitamin D synthesis, UVR exposure has beneficial effects on susceptibility and outcome to a variety of complex diseases. We describe evidence from studies in various diseases, but mainly from prostate cancer patients, that supports this hypothesis, but we emphasize that, although supportive data are available, the concept is unproven. Indeed, other explanations are possible. However, given the potentially important public health implications of the hypothesis and the potential for the development of novel therapeutic modalities, we believe the concept is worthy of further investigation.     

Photoimmunology: the mechanisms involved in immune modulation by UV radiation

Ultraviolet radiation (UVR) may be the most prevalent agent that man encounters in his environment. As a result, certain biological adaptations take advantage of the beneficial effects of UVR exposure, e.g. the photoactivation steps involved in vitamin D metabolism. In this regard, UVR plays an important role in maintaining our good health; however, it must be noted that UVR is potentially the most harmful naturally occurring agent in our environment. Thus, it appears that several mechanisms have evolved to protect us against the detrimental effects of UVR overexposure. Although epidermal melaninization or "tanning" may be the most obvious example of these processes, we would argue that adoptive mechanisms within the immune system also provide protection against UVR-induced skin damage. It is now known that UVR affects the distribution and functional activities of various immunocompetent cells within the skin, as well as modifying the production of inflammatory and hematopoietically active cytokines. This review will focus on the known mechanisms involved in the immune modulatory effects of UVR and how adoptive immune responses to UVR-induced skin damage contribute to specific pathological processes.     

Direct photolysis of chlorophenols in aqueous solutions by UV radiation from excilamps

Direct photolysis of 2- and 4-chlorophenol and 2,4-dichlorophenol in aqueous solutions by UV radiation from XeBr (282 nm) and KrCl (222 nm) excilamps at various pH values was subjected to a comparative study.