Serum vitamin D levels in office workers in a subtropical climate

Vitamin D is necessary to maintain healthy bones, and may prevent other chronic diseases. There is limited information regarding the vitamin D status of people living in climates with relatively high ambient ultraviolet radiation. We therefore aimed to determine serum 25(OH)D levels in a group of office-workers in subtropical Australia. We collected blood from 129 office workers in summer (n = 129) and 175 in winter (91 in both seasons). Serum 25(OH)D was estimated using a commercial chemiluminescent immunoassay and we asked participants to complete questionnaires about sun exposure and diet for the month prior to blood collection. Summer and winter mean serum 25(OH)D was 74 (95% CI 70-77) nmol L(-1) and 54 (95% CI 51-57) nmol L(-1), respectively. In summer, 14% of participants were classed as "insufficient," compared with 51% in winter. High 25(OH)D levels in summer were associated with time spent outdoors in nonpeak UV periods, while in winter high levels were associated with intake of vitamin D from food or supplements. The high prevalence of vitamin D insufficiency observed in this population highlights the need for further examination of the relation between sunlight and vitamin D production to enable more accurate sun exposure recommendations.     

Ultraviolet radiation exposure, vitamin D, and cancer

This paper reviews briefly the evidence for an association between various measures of UV radiation (UVR) exposure and the development of cancer. Issues such as data quality, study design, measurement variation, comparability of studies, and quantification of UV exposure in relation to skin cancer are discussed. A range of exposure, based on skin type, might be appropriate: from 5 min a day three times a week for light-skinned individuals and 10 min a day three times a week for darker-skinned individuals. These exposures translate into 13 h per year, for a light-skinned individual, leading to 650 h of exposure from birth to age 50.     

Standard ultraviolet daylight for nonextreme exposure conditions

The skin is exposed to ultraviolet radiation (UVR) from natural or artificial sources on a daily basis. The effects of chronic low dose exposure merit investigation, even when these effects are neither conspicuous nor clinically assessable. The purpose of the present study was to define a relative spectral UV irradiance that is representative of frequent nonextreme sun exposure conditions and therefore more appropriate for studies of the long-term and daily effects of solar UV on the skin. Solar spectral UV irradiance values were calculated for different dates and locations by using a radiative transfer model. The spectral irradiance values obtained when the solar elevation is lower than 45 degrees were averaged. An important feature is the dUVA (320-400 nm) to dUVB (290-320 nm) irradiance values ratio, which was found to be 27.3 for the overall average. When the months corresponding to extreme irradiance values (low or high) were excluded from the calculations, the dUVA to dUVB ratio ranged from 27.2 to 27.5. The mean spectral irradiance of the model presented here represents environmental UV exposure conditions and can be used both as a standard to investigate the biological effects of a nonextreme UVR and to assess the effectiveness of products for daily skin protection.     

The vitamin D debate: translating controlled experiments into reality for human sun exposure times

Exposure to sunlight, specifically the ultraviolet radiation, has both positive and negative health effects. Maximizing the benefits (vitamin D synthesis) while minimizing the damage is a multifaceted problem in which many of the elements are poorly quantified. Here we show how rigorously conducted large sample size laboratory studies of the effect of ultraviolet radiation dose on vitamin D status can be applied to real-life situations. This was achieved by modeling the radiation incident on different surfaces for different solar locations, and equating with the controlled exposures in the laboratory studies. Results from both model and experimental data show that relatively short exposures of a modest amount of unprotected skin to summer sunlight in northern climes, on a regular basis during lunchtime hours, increases vitamin D to sufficiency status (≥20 ng mL(-1) ) in the white Caucasian population. While both sun exposure conditions and human skin responses are variable in real life, these quantitative findings provide a guide for authorities devising sunlight exposure recommendations.     

Relationship between vitamin D status and skin phototype in general adult population

A link between bone mineral density and skin color has been reported recently, and pigmentation has been shown to affect cutaneous vitamin D production. In the present study, we investigated the relationship between phototype, global self-assessed sun exposure, geographical location and vitamin D serum levels in 1191 French adults. When the factors were analyzed separately, individuals with lower phototypes as well as those with lower sun exposure showed significantly lower levels of vitamin D than those with darker phototypes or those with higher sun exposure. However, when factors were analyzed as a whole, the vitamin D status was no longer linked with the phototype, but with sun exposure and geographical location. Since phototypes and global self-assessments of sun exposure were positively linked, our data suggest that lower vitamin D levels in fair-skinned individuals are due to their sun exposure behavior.     

Hydroxylation of a vitamin D A-ring fragment

Summary When the benzoate of (S)-(Z)-2-(5-(tert-butyldimethylsiloxy)-2-methylencyclohexyliden)-ethanol (5) is treated with 2.5 equivalents of Hg(OOCCF₃)₂ in dryTHF, a smooth and selective allylic hydroxylation occurs. The C-1 functionalized vitamin D A-ring synthon6 is isolated in 65 to 70% yield in a single step.

---

Hydroxylierung eines Vitamin D A-Ring-Fragments (Kurze Mitt.)

Zusammenfassung Umsetzung des Benzoats von (S)-(Z)-2-(5-(tert-Butyldimethylsiloxy)-2-methylencyclohexyliden)-ethanol (5) mit 2.5 Äquivalenten Hg(OOCCF₃)₂ in trockenemTHF führt zu einer selektiven allylischen Hydroxylierung. Damit ist das an C-1 funktionalisierte Vitamin D A-Ring-Fragment6 in einem einzigen Schritt in einer Ausbeute von 65 bis 70% zugänglich.

     

A behavioral model for estimating population exposure to solar ultraviolet radiation

Determining the variability of solar UV exposure of different members of a population by direct measurement demands high compliance over an extended period of time by a large number of people. An alternative approach is to model the variables that affect personal exposure and this is the basis of the method reported here, which uses a random sampling technique to explore variability of exposure at different times of the year by habitués. It is shown that there are large variations in daily personal erythemal exposure, more so for indoor workers living in northern Europe than those resident in Florida, which are due not only to seasonal changes in ambient, but just as importantly to seasonal variation in behavior. Not surprisingly, holiday and summer weekend exposure account for the largest daily UV doses. Northern Europeans who take their summer vacation in Florida can double their exposure during this period compared with holidaying at home and this illustrates just how important sun protection measures should be during recreational exposure in areas of high insolation if the annual UV burden is to be sensibly controlled.     

Synthesis of 1alpha-hydroxyvitamin D5 using a modified two wavelength photolysis for vitamin D formation

[reaction: see text] 1Alpha-hydroxyvitamin D5 (1) is a promising chemopreventive agent for breast cancer and is being developed as a drug. We report a synthesis for this vitamin D analogue which uses a photochemical method for the B-ring opening, leading to the conjugated triene system. The precursor 7-dehydrositosteryl acetate (4) obtained through a one-pot, five-step procedure, was completely free of the 4,6-diene isomer that usually forms in the 5,7-diene synthesis. The pre-vitamin isomer (11) was generated using a modified two-wavelength photolysis procedure that increases the yield for this step more than 3-fold compared to classically used photolysis. The 1alpha-hydroxylation step was performed on the 3-triethylsilyl-trans-vitamin D5 (17) obtained via the sulfur dioxide adduct of cis-vitamin D5, in an overall yield of 48%. Photoisomerization and deprotection completed the synthesis.     

The objective assessment of lifetime cumulative ultraviolet exposure for determining melanoma risk

Exposure to ultraviolet radiation has commonly been recognized as the most important environmental risk factor for melanoma. The measurement of UV exposure in humans, however, has proved challenging. Despite the general appreciation that an objective metric for individual UV exposure is needed to properly assess melanoma risk, little attention has been given to the issue of accuracy of UV exposure measurement. The present research utilized a GIS based historical UV exposure model (for which the accuracy of exposure estimates is known) and examined, in the case-control setting, the relative importance of UV exposure compared to self-reported time spent outdoors, in melanoma risk. UV estimates were coupled with residential histories of 820 representative melanoma cases among non-Hispanic white residents under 65 years of age from Los Angeles County and for 877 controls matched to cases by age, sex, race, and neighborhood of residence, to calculate the cumulative lifetime UV exposure and average annual UV exposure. For historical measures, when the participants resided outside the US, we also calculated UV estimates. While there was no increased risk of melanoma associated with self-reported time spent outdoors, the association between annual average UV exposure based on residential history and melanoma risk was substantial, as was the association between cumulative UV exposure based on residential history and melanoma. The time spent in outdoor activities appeared to have no significant effect on melanoma risk in any age strata, however, when adjusted for UV exposure based on residential history, time spent outdoors during young age significantly increased risk for melanoma. While there was some attenuation of risk when we excluded data from people resident overseas (as all other studies we are aware of have done), this did not significantly impact subsequent risk estimates of UV exposure on melanoma.     

Comparisons of estimated economic burdens due to insufficient solar ultraviolet irradiance and vitamin D and excess solar UV irradiance for the United States

Vitamin D sufficiency is required for optimal health, and solar ultraviolet B (UVB) irradiance is an important source of vitamin D. UVB and/or vitamin D have been found in observational studies to be associated with reduced risk for over a dozen forms of cancer, multiple sclerosis, osteoporotic fractures, and several other diseases. On the other hand, excess UV irradiance is associated with adverse health outcomes such as cataracts, melanoma, and nonmelanoma skin cancer. Ecologic analyses are used to estimate the fraction of cancer mortality, multiple sclerosis prevalence, and cataract formation that can be prevented or delayed. Estimates from the literature are used for other diseases attributed to excess UV irradiation, additional cancer estimates, and osteoporotic fractures. These results are used to estimate the economic burdens of insufficient UVB irradiation and vitamin D insufficiency as well as excess UV irradiation in the United States for these diseases and conditions. We estimate that 50,000-63,000 individuals in the United States and 19,000-25,000 in the UK die prematurely from cancer annually due to insufficient vitamin D. The U.S. economic burden due to vitamin D insufficiency from inadequate exposure to solar UVB irradiance, diet, and supplements was estimated at $40-56 billion in 2004, whereas the economic burden for excess UV irradiance was estimated at $6-7 billion. These results suggest that increased vitamin D through UVB irradiance, fortification of food, and supplementation could reduce the health care burden in the United States, UK, and elsewhere. Further research is required to confirm these estimates.     

Rational design of vitamin D3 analogues which selectively restore activity to a vitamin D receptor mutant associated with rickets

[formula: see text] Vitamin D3-resistant rickets (VDRR) is associated with mutations to the Vitamin D receptor (VDR) which effect ligand-dependent transactivation. Some VDRR associated mutants directly disrupt ligand binding. Using the reported VDR-1,25-dihydroxy vitamin D3 (1,25(OH)2D3) cocrystal structure, three 1,25(OH)2D3 analogues were designed to uniquely complement the rickets associated mutant VDR(Arg274-->Leu). The three analogues were 17 to 286 times more potent than 1,25(OH)2D3 with the mutant in cell-based assays and did not substantially activate cellular calcium influx.     

Youth solar ultraviolet radiation exposure, concurrent activities and sun-protective practices: a review

To assist standardization of procedures, facilitate comparisons, and help guide research efforts to optimally inform development of appropriately targeted interventions, there is a need to review methods used to quantify child and adolescent solar ultraviolet radiation (UV) exposure, related outdoor activities and sun-protective practices. This holistic approach is essential for comprehensive research that will provide all-inclusive, informative and meaningful messages for preventive measures of harmful UV exposure. Two databases were searched and 29 studies were retrieved, and these studies report measurement or assessment techniques documenting UV exposure patterns and related outdoor activities. Polysulfone film badges were the main measurement instrument used in 10 studies, with questionnaire, survey data, observation, a model, electronic dosimeters, biological dosimeters, colorimeter and UV colouring labels used in the remaining studies. Methods used to record activities included self-report, parental report, a logbook and observation. Measurement duration and unit of UV exposure varied in most studies, but a method common to 15 studies was measured UV exposure as a percentage of ambient UV. The studies reviewed do not provide sufficient information for the development and evaluation of targeted youth sun protection programs. Studies are required which document precise UV exposure, concurrent activities and sun protection usage for children and adolescents.     

Dual parallel mass spectrometry for lipid and vitamin D analysis

There are numerous options for mass spectrometric analysis of lipids, including different types of ionization, and a wide variety of experiments using different scan modes that can be conducted. Atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) provide complementary types of information that are both desirable. However, the duty cycle of the mass spectrometer places limits on the number of experiments that can be performed, and instruments usually employ only one type of ionization at a time. This work describes the approaches we have used that employ two mass spectrometers in parallel or in a column-switching configuration that allows multiple ionization modes and types of experiments to be conducted simultaneously during a single chromatographic run. These data demonstrate how use of two systems can reduce or eliminate the need for repeat injections and repetitive experiments. Approaches are described that employ two mass spectrometers connected in parallel as detectors for a single chromatographic system (LC1/MS2) or that employ two liquid chromatographs and two mass spectrometers in a column-switching arrangement (LC2/MS2). Examples of LC1/MS2 analyses of triacylglycerols (TAGs), sphingolipids, and vitamin D are given, as well as an example of an LC2/MS2 experiment that is used to perform analysis of both polar and non-polar lipids in a total lipid extract.     

Computational model for vitamin D deficiency using hair mineral analysis

Vitamin D deficiency is prevalent in the Arabian Gulf region, especially among women. Recent studies show that the vitamin D deficiency is associated with a mineral status of a patient. Therefore, it is important to assess the mineral status of the patient to reveal the hidden mineral imbalance associated with vitamin D deficiency. A well-known test such as the red blood cells is fairly expensive, invasive, and less informative. On the other hand, a hair mineral analysis can be considered an accurate, excellent, highly informative tool to measure mineral imbalance associated with vitamin D deficiency. In this study, 118 apparently healthy Kuwaiti women were assessed for their mineral levels and vitamin D status by a hair mineral analysis (HMA). This information was used to build a computerized model that would predict vitamin D deficiency based on its association with the levels and ratios of minerals. The first phase of the proposed model introduces a novel hybrid optimization algorithm, which can be considered as an improvement of Bat Algorithm (BA) to select the most discriminative features. The improvement includes using the mutation process of Genetic Algorithm (GA) to update the positions of bats with the aim of speeding up convergence; thus, making the algorithm more feasible for wider ranges of real-world applications. Due to the imbalanced class distribution in our dataset, in the second phase, different sampling methods such as Random Under-Sampling, Random Over-Sampling, and Synthetic Minority Oversampling Technique are used to solve the problem of imbalanced datasets. In the third phase, an AdaBoost ensemble classifier is used to predicting the vitamin D deficiency. The results showed that the proposed model achieved good results to detect the deficiency in vitamin D.     

Development and optimization of an LC-MS/MS-based method for simultaneous quantification of vitamin D2 , vitamin D3 , 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3

Simultaneous and accurate measurement of vitamin D and 25-hydroxyvitamin D in biological samples is a barrier limiting our ability to define "optimal" vitamin D status. Thus, our goal was to optimize conditions and evaluate an LC-MS method for simultaneous detection and quantification of vitamin D(2) , vitamin D(3) , 25-hydroxyvitamin D(2) and 25-hydroxyvitamin D(3) in serum. Extraction and separation of vitamin D forms were achieved using acetone liquid-liquid extraction and by a reversed phase C8 column, respectively. Detection was performed on a triple quadrupole tandem mass spectrometer (QQQ-MS/MS) equipped with atmospheric pressure photo ionization source. The LOQs for all analytes tested were 1 ng/mL for hydroxylated molecules and 2 ng/mL for the parent vitamin Ds. RSD at lower LOQ (2 ng/mL) and in medium (80 ng/mL) and high (200 ng/mL) quality control samples did not exceed 20 and 15% CV, respectively. Accuracy of the method for determination of hydroxylated molecules was also validated using National Institutes of Standards and Technology standard samples and found to be in the range of 90.9-111.2%. In summary, a sensitive and reproducible method is reported for simultaneous quantification of vitamin D(2) , vitamin D(3) , 25-hydroxyvitamin D(2) and 25-hydroxyvitamin D(3) molecules in biological samples.     

Effect of gender, season, and vitamin D status on bone biochemical markers in Saudi diabetes patients

Biochemical bone turnover markers (BTMs) provide important information on the diagnosis, therapy and monitoring of metabolic bone diseases. They are evident before measurable changes in bone mineral density (BMD) take place. A total of 35 adult Saudi patients (23 males; 12 females) with type 2 diabetes and diagnosed to be vitamin D deficient were recruited in this prospective study. Here we investigated the effects of gender, season, and vitamin D status on bone biochemical markers of bone remodeling. Anthropometry and blood samples were collected at different intervals. Metabolic parameters and bone biomarkers were measured routinely and by ELISA. Both males and females had a significant increase in their vitamin D status over time, but no significant changes in the bone biomarkers were observed in females. In males there was a significant increase in circulating levels of corrected calcium and OPN (p = 0.004 and 0.01 respectively) and a significant decrease in crosslaps (p = 0.005). In all subjects there was a modest but significant positive relationship between vitamin D status and OC (R = 0.34; p = 0.04). In conclusion, our study demonstrates that changes in bone remodeling markers are affected by season, gender, and possibly vitamin D status. This gender difference may well reflect the physiologic pathway responsible for the higher peak bone mass achieved in males compared to females.     

Characterization of chiral building blocks for vitamin D metabolites by DSC

The enantiometric purity of a vitamin D₃ metabolite was determined more exactly by means of DSC than by¹ H-NMR. The melting curve was analysed by the partial area method based on the Schröder-van Laar equation. In order to find a suitable method for separation(R)-2,3-dihydroxy-3-methylbutylp-toluenesulfonate from the racemate, the phase diagram of the enantiomers was evaluated from DSC results. The occurrence of a racemic compound was confirmed by an X-ray diffraction investigation of the racemate and the enantiomers. The conclusions are discussed in comparison with the results of previous investigations.

---

Zusammenfassung Die Enantiomeren-Reinheit des Vitamin D3-Metaboliten (R)-2,3-Dihydroxy-3-methylbutyl-p-toluensulfonat (R-I) lässt sich durch DSC genauer als mittels¹ H-NMR ermitteln. Dazu wird die Schmelzkurve nach der Partialflächenmethode ausgewertet, die auf der Schröder-van Laar'schen Gleichung beruht.Zum Auffinden einer geeigneten Methode für die Abtrennung des R-Enantiomeren aus dem Racemat wurde das Phasendiagramm der Enantiomeren aus DSC-Messungen konstruiert. Das Vorliegen einer racemischen Verbindung wurde durch Röntgenbeugungsuntersuchungen von Racemat und reinen Enantiomeren bestätigt. Die Ergebnisse werden mit denen früherer Untersuchungen verglichen.

---

D₃ , . , -. (R) -2,3--- -- , . . .

     

Calculated NMR as a tool for structural elucidation of jungianol and mutisianthol

Theoretical methods were used for the correct structure assignments of the natural products jungianol and mutisianthol. A three stage protocol for the calculation was used: a conformational search using molecular mechanics (MM3), a DFT (B3LYP) structure optimization and ab initio (HF/GIAO) or DFT (B3LYP/GIAO) calculation of magnetic properties.