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Sample records for 25-hydroxyvitamin d3 25-ohd3

  1. Biliary excretion of radioactivity after intravenous administration of (3H)25-hydroxyvitamin D3 in man

    SciTech Connect

    Ledger, J.E.; Watson, G.J.; Compston, J.E.

    1986-04-01

    The biliary excretion of radioactivity after intravenous (3H)25-hydroxyvitamin D3 was studied in nine patients with T-tube bile drainage. The mean +/- SD 24-hr radioactivity excretion in T-tube bile expressed as a percentage of the administered dose was 6.7 +/- 2.9%; after correction for incomplete bile collection, the value obtained was 16.0 +/- 11.1%. Chloroform solubility of biliary radioactivity increased from 27.4 +/- 8.9% to 72.9 +/- 10.1% following incubation with beta-glucuronidase. High-performance liquid chromatographic analysis of chloroform extracts of bile revealed that most of the eluted radioactivity was more polar than (3H)25-hydroxyvitamin D3. No free (3H)25-hydroxyvitamin D3 was demonstrated. Thus in man, most of the biliary radioactivity excreted following (3H)25-hydroxyvitamin D3 is in the form of water-soluble compounds, mainly glucuronides. However, our results suggest that glucuronides of metabolites other than 25-OHD3 are predominantly formed.

  2. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... (a) Product. 25-Hydroxyvitamin D3 (9,10-secocholesta-5,7,10(19)-triene-3β, 25-diol). (b) Conditions of use. This substance is generally recognized as safe as a source of vitamin D3 activity in feed...

  3. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DRINKING WATER OF ANIMALS Listing of Specific Substances Affirmed as GRAS § 584.725 25-Hydroxyvitamin D3... drinking water of broiler chickens when used in accordance with the limitations in paragraph (c) of this... exceed 69 ppb in feed or 34.5 ppb in drinking water. (ii) Adequate use directions to ensure that...

  4. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DRINKING WATER OF ANIMALS Listing of Specific Substances Affirmed as GRAS § 584.725 25-Hydroxyvitamin D3... drinking water of broiler chickens when used in accordance with the limitations in paragraph (c) of this... exceed 69 ppb in feed or 34.5 ppb in drinking water. (ii) Adequate use directions to ensure that...

  5. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DRINKING WATER OF ANIMALS Listing of Specific Substances Affirmed as GRAS § 584.725 25-Hydroxyvitamin D3... drinking water of broiler chickens when used in accordance with the limitations in paragraph (c) of this... exceed 69 ppb in feed or 34.5 ppb in drinking water. (ii) Adequate use directions to ensure that...

  6. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DRINKING WATER OF ANIMALS Listing of Specific Substances Affirmed as GRAS § 584.725 25-Hydroxyvitamin D3... drinking water of broiler chickens when used in accordance with the limitations in paragraph (c) of this... exceed 69 ppb in feed or 34.5 ppb in drinking water. (ii) Adequate use directions to ensure that...

  7. Human UGT1A4 and UGT1A3 Conjugate 25-Hydroxyvitamin D3: Metabolite Structure, Kinetics, Inducibility, and Interindividual Variability

    PubMed Central

    Wang, Zhican; Wong, Timothy; Hashizume, Takanori; Dickmann, Leslie Z.; Scian, Michele; Koszewski, Nicholas J.; Goff, Jesse P.; Horst, Ronald L.; Chaudhry, Amarjit S.; Schuetz, Erin G.

    2014-01-01

    25-Hydroxyvitamin D3 (25OHD3) is used as a clinical biomarker for assessment of vitamin D status. Blood levels of 25OHD3 represent a balance between its formation rate and clearance by several oxidative and conjugative processes. In the present study, the identity of human uridine 5′-diphosphoglucuronyltransferases (UGTs) capable of catalyzing the 25OHD3 glucuronidation reaction was investigated. Two isozymes, UGT1A4 and UGT1A3, were identified as the principal catalysts of 25OHD3 glucuronidation in human liver. Three 25OHD3 monoglucuronides (25OHD3-25-glucuronide, 25OHD3-3-glucuronide, and 5,6-trans-25OHD3-25-glucuronide) were generated by recombinant UGT1A4/UGT1A3, human liver microsomes, and human hepatocytes. The kinetics of 25OHD3 glucuronide formation in all systems tested conformed to the Michaelis-Menten model. An association between the UGT1A4*3 (Leu48Val) gene polymorphism with the rates of glucuronide formation was also investigated using human liver microsomes isolated from 80 genotyped livers. A variant allele dose effect was observed: the homozygous UGT1A4*3 livers (GG) had the highest glucuronidation activity, whereas the wild type (TT) had the lowest activity. Induction of UGT1A4 and UGT1A3 gene expression was also determined in human hepatocytes treated with pregnane X receptor/constitutive androstane receptor agonists, such as rifampin, carbamazepine, and phenobarbital. Although UGT mRNA levels were increased significantly by all of the known pregnane X receptor/constitutive androstane receptor agonists tested, rifampin, the most potent of the inducers, significantly induced total 25OHD3 glucuronide formation activity in human hepatocytes measured after 2, but not 4 and 24 hours, of incubation. Finally, the presence of 25OHD3-3-glucuronide in both human plasma and bile was confirmed, suggesting that the glucuronidation pathway might be physiologically relevant and contribute to vitamin D homeostasis in humans. PMID:24641623

  8. Model-based meta-analysis for development of a population-pharmacokinetic (PPK) model for Vitamin D3 and its 25OHD3 metabolite using both individual and arm-level data.

    PubMed

    Ocampo-Pelland, Alanna S; Gastonguay, Marc R; French, Jonathan F; Riggs, Matthew M

    2016-04-01

    Clinical studies investigating relationships between D3 and 25OHD3 vary in dosing regimen, assays, demographics, and control of exogenous D3. This leads to uncertain and conflicting exposure-related associations with D3 and 25OHD3. To elucidate this parent-metabolite system, a PPK model was developed to predict mean D3 and 25OHD3 exposure from varied doses and administration routes. Sources of exposure variability related to metabolite baseline, weight, and assay type were explored. Specific search criteria were used in PUBMED to identify public source PK data pertaining to D3 and 25OHD3 in healthy or osteoporotic populations. Overall 57 studies representing 5395 individuals were selected, including 25 individual-level profiles and treatment-arm data. IV, oral, single and multiple dose data were used, with D3 and 25OHD3 dosing. A nonlinear mixed effects model was developed to simultaneously model PK dispositions of D3 and 25OHD3 (NONMEM v7.2), which were described by 2-compartment models with nonlinear and linear clearances, respectively. Proportional and additive assay variances were included on the 25OHD3 prediction. Unit-level random effects were weighted by treatment-arm size. D3 model estimates, relative to bioavailability were: maximum rate of metabolism ([Formula: see text], 1.62 nmol/h), Michaelis-Menten constant ([Formula: see text], 6.39 nmol/L), central volume of distribution ([Formula: see text], 15.5 L), intercompartmental clearance ([Formula: see text], 0.185 L/h), peripheral volume of distribution ([Formula: see text], 2333 L/h), and baseline concentration ([Formula: see text], 3.75 nmol/L). For 25OHD3 ([Formula: see text] = metabolite): [Formula: see text] = 0.0153 L/h, [Formula: see text] = 4.35 L, [Formula: see text] = 6.87 L, [Formula: see text] = 0.0507 L/h. Simulations of 25OHD3 concentration indicated an inverse relationship between 25OHD3 baseline and response, as well as a less than proportional 25OHD3 response. Estimation of assay bias

  9. Chromatographic separation of PTAD-derivatized 25-hydroxyvitamin D3 and its C-3 epimer from human serum and murine skin.

    PubMed

    Teegarden, Matthew D; Riedl, Kenneth M; Schwartz, Steven J

    2015-06-01

    The detection of 25-hydroxyvitamin D at low levels in biological samples is facilitated by the use of chemical derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) in concert with liquid chromatography-tandem mass spectrometry (LC-MS/MS). This mode of analysis is notably hampered by chromatographic co-elution of 25-hydroxyvitamin D3 (25OHD3) and its C-3 epimer (C3epi). The objective of this work was to improve upon current LC-MS/MS methods used for the analysis of PTAD-derivatized 25-hydroxyvitamin D3 by resolving it from C3epi. Additionally, the applicability of this method in human serum and murine skin was investigated. C18 columns of increasing length and varying particle sizes were assessed for performance using a mixed standard of PTAD-derivatized 25OHD3 and C3epi. Serum samples were processed using solid phase extraction, and skin was powdered and extracted for lipophilic compounds. The samples were derivatized with PTAD and subsequently analyzed using isotope dilution LC-MS/MS with atmospheric pressure chemical ionization operated in positive mode. Near baseline resolution of PTAD-25OHD3 from PTAD-C3epi was achieved on a 250mm C18 column with 3μm sized particles. This separation allowed for detection and quantification of both metabolites in serum and skin samples. PTAD-C3epi represented a significant confounding analyte in all samples, and comprised up to 20% of the status measurement in skin. This method is a significant improvement on the chromatography of PTAD-derivatized vitamin D metabolites that could greatly influence the assessment of vitamin D status and C3epi biology in low abundance samples.

  10. Parathyroidectomy reduces 25-hydroxyvitamin D3-1 alpha-hydroxylase activity in the hypocalcemic vitamin D-deficient chick.

    PubMed Central

    Booth, B E; Tsai, H C; Morris, R C

    1977-01-01

    To test the hypothesis that in the vitamin D-deficient state the activity of 25-hydroxyvitamin D3-1 alpha-hydroxylase (25-OHD3-1 alpha-hydroxylase) is modulated by parathyroid hormone and the plasma concentration of phosphate only in the presence of small amounts of 1,25-dihydroxyvitamin D3 (or some other metabolite of vitamin D), we measured the activity of this enzyme 24 h after parathyroidectomy (PTX) in frankly hypocalcemic, vitamin D-deficient chicks that were not supplemented with vitamin D or one of its metabolites. The otherwise predictable complications of PTX in this metabolic setting (hypocalcemia of increasing severity, tetany, moribundity, and death) were prevented by continuous intravenous administration of calcium (as a solution of calcium chloride/calcium gluconate 1:1) through a catheter in the external jugular vein placed at the time of PTX. The findings were as follows: (a) The activity of 25-OHD3-1 alpha-hydroxylase was significantly less in the parathyroidectomized group than in the sham-operated control chicks (P less than 0.001). (b) The reductive effect of PTX on the activity of this enzyme was significantly attenuated when hypophosphatemia was increased in severity by administration of glucose. (c) In the post-PTX state the activity of 25-OHD3-1 alpha-hydroxylase and plasma concentration of phosphate were significantly, inversely related (P less than 0.001). (d) In the sham-operated control group the activity of this enzyme and the plasma concentration of phosphate were not significantly correlated. These findings indicate that in the vitamin D-deficient state, both circulating parathyroid hormone and the plasma concentration of phosphate can significantly modulate the activity of 25-OHD3-1 alpha-hydroxylase in the absence of vitamin D or its metabolites. The findings also suggest that in the vitamin D-deficient state the plasma concentration of phosphate modulates the activity of this enzyme only when the concentration of circulating

  11. Local Sustained Delivery of 25-Hydroxyvitamin D3 for Production of Antimicrobial Peptides

    PubMed Central

    Jiang, Jiang; Chen, Guojun; Shuler, Franklin D.; Wang, Chi-Hwa; Xie, Jingwei

    2015-01-01

    Purpose This study seeks to develop fiber membranes for local sustained delivery of 25-hydroxyvitamin D3 to induce the expression and secretion of LL-37 at or near the surgical site, which provides a novel therapeutic approach to minimize the risk of infections. Methods 25-hydroxyvitamin D3 loaded poly(L-lactide) (PLA) and poly(ε-caprolactone) (PCL) fibers were produced by electrospinning. The morphology of obtained fibers was characterized using atomic force microscope (AFM) and scanning electron microscope (SEM). 25-hydroxyvitamin D3 releasing kinetics were quantified by enzyme-linked immunosorbent assay (ELISA) kit. The expression of cathelicidin (hCAP 18) and LL-37 was analyzed by immunofluorescence staining and ELISA kit. The antibacterial activity test was conducted by incubating pseudomonas aeruginosa in a monocytes’ lysis solution. Results AFM images suggest that the surface of PCL fibers is smooth, however, the surface of PLA fibers is relatively rough, in particular, after encapsulation of 25-hydroxyvitamin D3. The duration of 25-hydroxyvitamin D3 release can last more than 4 weeks for all the tested samples. Plasma treatment can promote the release rate of 25-hydroxyvitamin D3. Human keratinocytes and monocytes express significantly higher levels of hCAP18/LL-37 after incubation with plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers than the cells incubated with around 10 times amount of free drug. After incubation with this fiber formulation for 5 days LL-37 in the lysis solutions of U937 cells can effectively kill the bacteria. Conclusions plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers induce significantly higher levels of antimicrobial peptide production in human keratinocytes and monocytes without producing cytotoxicity. PMID:25773720

  12. Kinetics of intravenously administered 25-hydroxyvitamin D3 in sheep and the effect of exposure to ultraviolet radiation

    SciTech Connect

    Hidiroglou, M.

    1987-09-01

    This report describes studies of 25-hydroxyvitamin D3 (25OHD3) kinetics in 10 yearling crossbred wethers (40 to 52 kg body weight) administered (/sup 3/H) 25-hydroxyvitamin D3 (( /sup 3/H) 250HD3). The wethers were divided into two groups of five before dosing with the labeled compound: Group 1 wethers were exposed 2 h daily for 8 to 10 wk to ultraviolet radiation from fluorescent sunlamps. Plasma 250HD3 increased from 13 to 31 ng/ml by d 25 and then remained at a steady-state concentration until d 70. In the non-ultraviolet-exposed wethers (Group 2), plasma 250HD3 averaged 13.2 ng/ml and did not change over the course of the experiment. Six weeks after the start of the experiment three wethers from each group were injected intravenously with 50 microCi of (/sup 3/H)250HD3, and the other two wethers from each group were similarly dosed 2 wk later. Blood was drawn at suitable time intervals for up to 240 h post-dosing. The kinetic data were satisfied by curve-fitting the data to a two-compartment, pharmacokinetic mathematical model. Individual and mean values for these kinetic analyses are presented with their statistical analyses. Physiological half-life of the tritiated 2500 HD3 in wethers exposed to ultraviolet irradiation was 388 +/- 26.4 h (means +/- SE); in the control it was 393 +/- 29.6 h (P greater than .05). In the wethers exposed to ultraviolet the elimination and clearance rates of 250HD3 were significantly greater than in the control wethers. A two-compartment model provided an acceptable description of 250HD3 disposition kinetics in wethers. Turnover rate constants did not seem to change, but changes were due to increased pool size in the irradiated wethers.

  13. Photoaffinity labeling of serum vitamin D binding protein by 3-deoxy-3-azido-25-hydroxyvitamin D3

    SciTech Connect

    Link, R.P.; Kutner, A.; Schnoes, H.K.; DeLuca, H.F.

    1987-06-30

    3-Deoxy-3-azido-25-hydroxyvitamin D3 was covalently incorporated in the 25-hydroxyvitamin D3 binding site of purified human plasma vitamin D binding protein. Competition experiments showed that 3-deoxy-3-azido-25-hydroxyvitamin D3 and 25-hydroxyvitamin D3 bind at the same site on the protein. Tritiated 3-deoxy-3-azido-25-hydroxyvitamin D3 was synthesized from tritiated 25-hydroxyvitamin D3, retaining the high specific activity of the parent compound. The tritiated azido label bound reversibly to human vitamin D binding protein in the dark and covalently to human vitamin D binding protein after exposure to ultraviolet light. Reversible binding of tritiated 3-deoxy-3-azido-25-hydroxyvitamin D3 was compared to tritiated 25-hydroxyvitamin D3 binding to human vitamin D binding protein. Scatchard analysis of the data indicated equivalent maximum density binding sites with a KD,app of 0.21 nM for 25-hydroxyvitamin D3 and a KD,app of 1.3 nM for the azido derivative. Covalent binding was observed only after exposure to ultraviolet irradiation, with an average of 3% of the reversibly bound label becoming covalently bound to vitamin D binding protein. The covalent binding was reduced 70-80% when 25-hydroxyvitamin D3 was present, indicating strong covalent binding at the vitamin D binding site of the protein. When tritiated 3-deoxy-3-azido-25-hydroxyvitamin D3 was incubated with human plasma in the absence and presence of 25-hydroxyvitamin D3, 12% of the azido derivative was reversibly bound to vitamin D binding protein. After ultraviolet irradiation, four plasma proteins covalently bound the azido label, but vitamin D binding protein was the only protein of the four that was unlabeled in the presence of 25-hydroxyvitamin D3.

  14. Regulation of Mycobacterium-specific mononuclear cell responses by 25-hydroxyvitamin D3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), has been shown to be an important regulator of innate and adaptive immune function. In addition, synthesis of 1,25(OH)2D3 from 25-hydroxyvitamin D3 (25[OH]D3) by the enzyme 1alpha-hydroxylase in monocytes upon activation by TLR...

  15. Treatment of an intramammary bacterial infection with 25-hydroxyvitamin D3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deficiency of serum levels of 25-hydroxyvitamin D3 has been correlated with increased risk of infectious diseases, such as tuberculosis and influenza. A plausible reason for this association is that expression of genes encoding important antimicrobial proteins depends on concentrations of 1,25-dihyd...

  16. 25-Hydroxyvitamin D3-deficiency enhances oxidative stress and corticosteroid resistance in severe asthma exacerbation.

    PubMed

    Lan, Nan; Luo, Guangyan; Yang, Xiaoqiong; Cheng, Yuanyuan; Zhang, Yun; Wang, Xiaoyun; Wang, Xing; Xie, Tao; Li, Guoping; Liu, Zhigang; Zhong, Nanshan

    2014-01-01

    Oxidative stress plays a significant role in exacerbation of asthma. The role of vitamin D in oxidative stress and asthma exacerbation remains unclear. We aimed to determine the relationship between vitamin D status and oxidative stress in asthma exacerbation. Severe asthma exacerbation patients with 25-hydroxyvitamin D3-deficiency (V-D deficiency) or 25-hydroxyvitamin D-sufficiency (V-D sufficiency) were enrolled. Severe asthma exacerbation with V-D-deficiency showed lower forced expiratory volume in one second (FEV1) compared to that with V-D-sufficiency. V-D-deficiency intensified ROS release and DNA damage and increased TNF-α, OGG1 and NFκB expression and NFκB phosphorylation in severe asthma exacerbation. Supplemental vitamin D3 significantly increased the rates of FEV1 change and decreased ROS and DNA damage in V-D-deficiency. Vitamin D3 inhibited LPS-induced ROS and DNA damage and were associated with a decline in TNF-α and NFκB in epithelial cells. H2O2 reduces nuclear translocation of glucocorticoid receptors in airway epithelial cell lines. V-D pretreatment enhanced the dexamethasone-induced nuclear translocation of glucocorticoid receptors in airway epithelial cell lines and monocytes from 25-hydroxyvitamin D3-deficiency asthma patients. These findings indicate that V-D deficiency aggravates oxidative stress and DNA damage, suggesting a possible mechanism for corticosteroid resistance in severe asthma exacerbation.

  17. Independent associations of polymorphisms in vitamin D binding protein (GC) and vitamin D receptor (VDR) genes with obesity and plasma 25OHD3 levels demonstrate sex dimorphism.

    PubMed

    Almesri, Norah; Das, Nagalla S; Ali, Muhallab E; Gumaa, Khalid; Giha, Hayder Ahmed

    2016-04-01

    We investigated a possible association between polymorphisms in vitamin D binding protein (GC) and vitamin D receptor (VDR) genes and obesity in Bahraini adults. For this purpose, 406 subjects with varying body mass indexes (BMIs) were selected. Plasma levels of 25-hydroxyvitamin D3 (25OHD3) were measured by chemiluminescence immunoassay. Six single nucleotide polymorphisms, 2 in the VDR gene (rs731236 TC and rs12721377 AG) and 4 in the GC gene (rs2282679 AC, rs4588 CA, rs7041 GT, and rs2298849 TC), were genotyped by real-time polymerase chain reaction. We found that the rs7041 minor allele (G) and rare genotype (GG) were associated with higher BMI (p = 0.007 and p = 0.012, respectively), but they did not influence 25OHD3 levels. However, the minor alleles of rs2282679 (A) and rs4588 (C) were associated with low 25OHD3 plasma levels (p = 0.039 and p = 0.021, respectively), but not with BMI. Having categorized the subjects based on their sex, we found that (i) rs7041 GG associated with high BMI in females (p = 0.003), (ii) rs4588 CC associated with high BMI in females (p = 0.034) and low 25OHD3 levels in males (p = 0.009), and (iii) rs12721377 AA associated with low 25OHD3 levels in females (p = 0.039). Notably, none of the common haplotypes (6 in the GC gene and 3 in the VDR gene) were associated with BMI. Therefore, polymorphisms in the GC (rs2282679, rs4588, rs7041) and VDR (rs12721377) genes were independently associated with obesity and 25OHD3 levels with a clear sex dimorphism.

  18. Serum 25-Hydroxyvitamin D3 and Mammography Density among Mexican Women.

    PubMed

    Amadou, Amina; Biessy, Carine; Rinaldi, Sabina; Fedirko, Veronika; Assi, Nada; Lajous, Martin; Ortiz-Panozo, Eduardo; Yunes, Elsa; Lopez-Ridaura, Ruy; Torres-Mejia, Gabriela; Romieu, Isabelle

    2016-01-01

    Low circulating levels of vitamin D and high mammographic density (MD) have been associated with higher risk of breast cancer. Although some evidence suggested an inverse association between circulating vitamin D and MD, no studies have investigated this association among Mexican women. We examined whether serum 25-hydroxyvitamin D3 [25(OH)D3] levels were associated with MD in a cross-sectional study nested within the large Mexican Teacher's Cohort. This study included 491 premenopausal women with a mean age of 42.9 years. Serum 25(OH)D3 levels were measured by liquid chromatography/tandem mass spectrometry. Linear regression and non-linear adjusted models were used to estimate the association of MD with serum 25(OH)D3. Median serum 25(OH)D3 level was 27.3 (23.3-32.8) (ng/ml). Forty one (8%) women had 25(OH)D3 levels in the deficient range (< 20 ng/ml). Body mass index (BMI) and total physical activity were significantly correlated with 25(OH)D3 (r = -0.109, P = 0.019 and r = 0.095, P = 0.003, respectively). In the multivariable linear regression, no significant association was observed between 25(OH)D3 levels and MD overall. However, in stratified analyses, higher serum 25(OH)D3 levels (≥27.3 ng/ml) were significantly inversely associated with percent MD among women with BMI below the median (β = -0.52, P = 0.047). Although no significant association was observed between serum 25(OH)D3 and percent MD in the overall population, specific subgroups of women may benefit from higher serum 25(OH)D3 levels. PMID:27564705

  19. Type of dietary fat is associated with the 25-hydroxyvitamin D3 increment in response to vitamin D supplementation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mono- and polyunsaturated fats may have opposing effects on vitamin D absorption. The purpose of this study was to determine whether intakes of different dietary fats are associated with the increase in serum 25-hydroxyvitamin D (25OHD) following supplementation with vitamin D3. This analysis was co...

  20. Role of 25-hydroxyvitamin D3 dose in determining rat 1,25-dihydroxyvitamin D3 production

    SciTech Connect

    Vieth, R.; McCarten, K.; Norwich, K.H. )

    1990-05-01

    To understand the relationships among (1) the dose of 25-hydroxyvitamin D (25(OH)D) in vivo, (2) the activity of 1-hydroxylase in renal mitochondria, and (3) the production of 1,25-dihydroxyvitamin D (1,25(OH)2D) in vivo, we gave rats different chronic or acute doses of 25-hydroxyvitamin D3 (25(OH)D3). We followed the metabolism of intracardially administered (25-hydroxy-26,27-methyl-3H)cholecalciferol (25(OH)(3H)D3) for 24 h before killing by measuring extracts of serum by chromatography. Specific activity of 1-hydroxylase in kidney was measured at death. In rats given 0-2,000 pmol 25(OH)D3 chronically by mouth, there was a dose-dependent decline in the percent of serum radioactivity made up of 1,25-dihydroxy-(26,27-methyl-3H)cholecalciferol (1,25(OH)2(3H)D3) as well as a decline in mitochondrial 1-hydroxylase, and these correlated significantly (r = 0.83, P less than 0.001). Serum %1,25(OH)2(3H)D3 in this experiment ranged from 0.8 to 42%. A small part of this range could be accounted for by a faster metabolic clearance rate (MCR) of 1,25(OH)2D3 from rats supplemented with 25(OH)D3 (MCR, 2.12 +/- 0.10 ml/min) compared with rats restricted in vitamin D (MCR, 0.94 +/- 0.06 ml/min, P less than 0.001). The activity of 1-hydroxylase was by far the major factor determining serum %1,25(OH)2(3H)D3. When different acute doses of 25(OH)D3 were given to rats with identical specific activities of 1-hydroxylase, the resulting 1,25(OH)2D3 concentrations in serum correlated with the 25(OH)D3 dose (r = 0.99, P less than 0.001). We conclude that the behavior of 1-hydroxylase in vivo is analogous to the classic behavior in vitro of an enzyme functioning below its Michaelis constant (Km). The amount of 1-hydroxylase present in renal mitochondria determines the fraction (not simply the quantity) of 25(OH)D metabolized to 1,25(OH)2D3 in vivo.

  1. 25-Hydroxyvitamin D3 Deficiency Independently Predicts Cognitive Impairment in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Tay, Sen Hee; Ho, Chung Shun; Ho, Roger Chun-Man; Mak, Anselm

    2015-01-01

    Objectives Cognitive dysfunction has been reported in 20–80% of SLE patients. Converging evidence has indicated the importance of vitamin D as a neuroimmunomodulator for cognitive function. In this study, we evaluated the relationship between vitamin D and cognitive dysfunction. Methods Consecutive age- and gender-matched SLE patients and healthy controls (HCs) were administered Automated Neuropsychological Assessment Metrics in this cross-sectional study. The primary outcome was the total throughput score (TTS). Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). Levels of 25-hydroxyvitamin D [25(OH)D3 and total 25(OH)D] were measured using Liquid Chromatography-Tandem Mass Spectrometry. Results In total, 61 SLE patients and 61 HCs were studied. SLE patients scored significantly lower than HCs in the TTS (p = 0.004). There were no statistically significant differences in 25(OH)D3 levels, total 25(OH)D levels and total 25(OH)D deficiency between SLE patients and HCs. However, more SLE patients had 25(OH)D3 deficiency compared to HCs [12 (19.7%) versus 2 (3.3%), p = 0.003]. Deficiency of 25(OH)D3 (β = -63.667, SE = 27.456, p = 0.025), but not other vitamin D variables, independently predicted worse TTS after adjusting for age, education, gender, ethnicity, HADS-Total, duration of SLE, SELENA-SLEDAI, SLICC/ACR Damage Index and cumulative steroid dose in SLE patients. Age (β = -4.261, SE = 0.866, p < 0.001) was the only predictor of TTS after adjusting for education, gender, ethnicity, HADS-Total, vitamin D levels or status in HCs. Conclusions Deficiency of 25(OH)D3, a potentially modifiable risk factor, independently predicted cognitive impairment in SLE patients. PMID:26636681

  2. Associations between blood persistent organic pollutants and 25-hydroxyvitamin D3 in pregnancy.

    PubMed

    Morales, Eva; Gascon, Mireia; Martinez, David; Casas, Maribel; Ballester, Ferran; Rodríguez-Bernal, Clara L; Ibarluzea, Jesus; Marina, Loreto Santa; Espada, Mercedes; Goñi, Fernando; Vizcaino, Esther; Grimalt, Joan O; Sunyer, Jordi

    2013-07-01

    Persistent organic pollutants (POPs) are suggested to contribute to lower vitamin D levels; however, studies in humans are scarce and have never focused on pregnancy, a susceptibility period for vitamin D deficiency. We investigated whether serum levels of POPs were associated with circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration in pregnancy. Cross-sectional associations of serum concentrations of eight POPs with plasma 25(OH)D3 concentration were analyzed in 2031 pregnant women participating in the Spanish population-based cohort INfancia y Medio Ambiente (INMA) Project. Serum concentrations of POPs were measured by gas chromatography and plasma 25(OH)D3 concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.3±1.5weeks of gestation). Multivariable regression models were performed to assess the relationship between blood concentrations of POPs and 25(OH)D3. An inverse linear relationship was found between serum concentration of PCB180 and circulating 25(OH)D3. Multivariate linear regression models showed higher PCB180 levels to be associated with lower 25(OH)D3 concentration: quartile Q4 vs. quartile Q1, coefficient=-1.59, 95% CI -3.27, 0.08, p trend=0.060. A non-monotonic inverse relationship was found between the sum of predominant PCB congeners (PCB 180, 153 and 138) and 25(OH)D3 concentration: coefficient (95% CI) for quartile Q2 vs. Q1 [-0.50 (-1.94, 0.94)], quartile Q3 vs. Q1 [-1.56 (-3.11, -0.02)] and quartile Q4 vs. Q1 [-1.21 (-2.80, 0.38)], p trend=0.081. No significant associations were found between circulating 25(OH)D3 and serum levels of p,p'-DDE, p,p'-DDT, HCB, and ß-HCH. Our results suggest that the background exposure to PCBs may result in lower 25(OH)D3 concentration in pregnant women.

  3. Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase.

    PubMed

    Zehnder, D; Bland, R; Williams, M C; McNinch, R W; Howie, A J; Stewart, P M; Hewison, M

    2001-02-01

    The mitochondrial enzyme 25-hydroxyvitamin D(3)-1 alpha-hydroxylase (1 alpha-hydroxylase) plays an important role in calcium homeostasis by catalyzing synthesis of the active form of vitamin D, 1,25-dihydroxyvitamin D(3), in the kidney. However, enzyme activity assays indicate that 1 alpha-hydroxylase is also expressed in a variety of extrarenal tissues; recent cloning of cDNAs for 1 alpha-hydroxylase in different species suggests that a similar gene product is found at both renal and extrarenal sites. Using specific complementary ribonucleic acid probes and antisera to 1 alpha-hydroxylase, we have previously reported the distribution of messenger ribonucleic acid and protein for the enzyme along the mouse and human nephron. Here we describe further immunohistochemical and Western blot analyses that detail for the first time the extrarenal distribution of 1 alpha-hydroxylase in both normal and diseased tissues. Specific staining for 1 alpha-hydroxylase was detected in skin (basal keratinocytes, hair follicles), lymph nodes (granulomata), colon (epithelial cells and parasympathetic ganglia), pancreas (islets), adrenal medulla, brain (cerebellum and cerebral cortex), and placenta (decidual and trophoblastic cells). Further studies using psoriatic skin highlighted overexpression of 1 alpha-hydroxylase throughout the dysregulated stratum spinosum. Increased expression of skin 1alpha-hydroxylase was also associated with sarcoidosis. In lymph nodes and skin from these patients 1 alpha-hydroxylase expression was observed in cells positive for the surface antigen CD68 (macrophages). The data presented here confirm the presence of protein for 1 alpha-hydroxylase in several extrarenal tissues, such as skin, placenta, and lymph nodes. The function of this enzyme at novel extrarenal sites, such as adrenal medulla, brain, pancreas, and colon, remains to be determined. However, the discrete patterns of staining in these tissues emphasizes a possible role for 1 alpha

  4. Serum 25-Hydroxyvitamin D3 Levels Are Associated With Breslow Thickness at Presentation and Survival From Melanoma

    PubMed Central

    Newton-Bishop, Julia A.; Beswick, Samantha; Randerson-Moor, Juliette; Chang, Yu-Mei; Affleck, Paul; Elliott, Faye; Chan, May; Leake, Susan; Karpavicius, Birute; Haynes, Sue; Kukalizch, Kairen; Whitaker, Linda; Jackson, Sharon; Gerry, Edwina; Nolan, Clarissa; Bertram, Chandra; Marsden, Jerry; Elder, David E.; Barrett, Jennifer H.; Bishop, D. Timothy

    2009-01-01

    Purpose A cohort study was carried out to test the hypothesis that higher vitamin D levels reduce the risk of relapse from melanoma. Methods A pilot retrospective study of 271 patients with melanoma suggested that vitamin D may protect against recurrence of melanoma. We tested these findings in a survival analysis in a cohort of 872 patients recruited to the Leeds Melanoma Cohort (median follow-up, 4.7 years). Results In the retrospective study, self-reports of taking vitamin D supplements were nonsignificantly correlated with a reduced risk of melanoma relapse (odds ratio = 0.6; 95% CI, 0.4 to 1.1; P = .09). Nonrelapsers had higher mean 25-hydroxyvitamin D3 levels than relapsers (49 v 46 nmol/L; P = .3; not statistically significant). In the cohort (prospective) study, higher 25-hydroxyvitamin D3 levels were associated with lower Breslow thickness at diagnosis (P = .002) and were independently protective of relapse and death: the hazard ratio for relapse-free survival (RFS) was 0.79 (95% CI, 0.64 to 0.96; P = .01) for a 20 nmol/L increase in serum level. There was evidence of interaction between the vitamin D receptor (VDR) BsmI genotype and serum 25-hydroxyvitamin D3 levels on RFS. Conclusion Results from the retrospective study were consistent with a role for vitamin D in melanoma outcome. The cohort study tests this hypothesis, providing evidence that higher 25-hydroxyvitamin D3 levels, at diagnosis, are associated with both thinner tumors and better survival from melanoma, independent of Breslow thickness. Patients with melanoma, and those at high risk of melanoma, should seek to ensure vitamin D sufficiency. Additional studies are needed to establish optimal serum levels for patients with melanoma. PMID:19770375

  5. Photoactivable analogs for labeling 25-hydroxyvitamin D3 serum binding protein and for 1,25-dihydroxyvitamin D3 intestinal receptor protein

    NASA Technical Reports Server (NTRS)

    Kutner, A.; Link, R. P.; Schnoes, H. K.; DeLuca, H. F.

    1986-01-01

    3-Azidobenzoates and 3-azidonitrobenzoates of 25-hydroxyvitamin D3 as well as 3-deoxy-3-azido-25-hydroxyvitamin D3 and 3-deoxy-3-azido-1,25-dihydroxyvitamin D3 were prepared as photoaffinity labels for vitamin D serum binding protein and 1,25-dihydroxyvitamin D3 intestinal receptor protein. The compounds prepared were easily activated by short- or long-wavelength uv light, as monitored by uv and ir spectrometry. The efficacy of the compounds to compete with 25-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 for the binding site of serum binding protein and receptor, respectively, was studied to evaluate the vitamin D label with the highest affinity for the protein. The presence of an azidobenzoate or azidonitrobenzoate substituent at the C-3 position of 25-OH-D3 significantly decreased (10(4)- to 10(6)-fold) the binding activity. However, the labels containing the azido substituent attached directly to the vitamin D skeleton at the C-3 position showed a high affinity, only 20- to 150-fold lower than that of the parent compounds with their respective proteins. Therefore, 3-deoxy-3-azidovitamins present potential ligands for photolabeling of vitamin D proteins and for studying the structures of the protein active sites.

  6. Primary Human Osteoblasts in Response to 25-Hydroxyvitamin D3, 1,25-Dihydroxyvitamin D3 and 24R,25-Dihydroxyvitamin D3

    PubMed Central

    van der Meijden, Karen; Lips, Paul; van Driel, Marjolein; Heijboer, Annemieke C.; Schulten, Engelbert A. J. M.; den Heijer, Martin; Bravenboer, Nathalie

    2014-01-01

    The most biologically active metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has well known direct effects on osteoblast growth and differentiation in vitro. The precursor 25-hydroxyvitamin D3 (25(OH)D3) can affect osteoblast function via conversion to 1,25(OH)2D3, however, it is largely unknown whether 25(OH)D3 can affect primary osteoblast function on its own. Furthermore, 25(OH)D3 is not only converted to 1,25(OH)2D3, but also to 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) which may have bioactivity as well. Therefore we used a primary human osteoblast model to examine whether 25(OH)D3 itself can affect osteoblast function using CYP27B1 silencing and to investigate whether 24R,25(OH)2D3 can affect osteoblast function. We showed that primary human osteoblasts responded to both 25(OH)D3 and 1,25(OH)2D3 by reducing their proliferation and enhancing their differentiation by the increase of alkaline phosphatase, osteocalcin and osteopontin expression. Osteoblasts expressed CYP27B1 and CYP24 and synthesized 1,25(OH)2D3 and 24R,25(OH)2D3 dose-dependently. Silencing of CYP27B1 resulted in a decline of 1,25(OH)2D3 synthesis, but we observed no significant differences in mRNA levels of differentiation markers in CYP27B1-silenced cells compared to control cells after treatment with 25(OH)D3. We demonstrated that 24R,25(OH)2D3 increased mRNA levels of alkaline phosphatase, osteocalcin and osteopontin. In addition, 24R,25(OH)2D3 strongly increased CYP24 mRNA. In conclusion, the vitamin D metabolites 25(OH)D3, 1,25(OH)2D3 and 24R,25(OH)2D3 can affect osteoblast differentiation directly or indirectly. We showed that primary human osteoblasts not only respond to 1,25(OH)2D3, but also to 24R,25(OH)2D3 by enhancing osteoblast differentiation. This suggests that 25(OH)D3 can affect osteoblast differentiation via conversion to the active metabolite 1,25(OH)2D3, but also via conversion to 24R,25(OH)2D3. Whether 25(OH)D3 has direct actions on osteoblast function needs further

  7. Conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 in renal slices from the rat

    SciTech Connect

    Armbrecht, H.J.; Zenser, T.V.; Davis, B.B.

    1981-07-01

    Isolated renal cortical slices were used to study the conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25)(OH2)D3) by the rat kidney. Production of 1,25-(OH)2D3 and 24,25-(OH)2D3 was linear with time (30-90 min) and tissue weight (40-250 mg). Production of 1,25-(OH)2D3 was greatest (134 +/- 17 pg/mg tissue.h) in animals fed a low calcium, vitamin D-deficient diet. The greatest 24,25-(OH)2D3 production (106 +/- 17 pg/mg tissue.h) was seen in animals fed a high calcium, vitamin D-replete diet, 1,25-(OH)2D3 production was reduced to 23% of maximum by the addition of 1.2% calcium or 0.8% strontium to the vitamin D-deficient, low calcium diet. Production of 1,25-(OH)2D3 and 24,25-(OH)2D3 was greatly reduced in renal cortical slices that had been heated before incubation. Slices of renal medulla produced only small amounts of 1,25-(OH)2D3 compared to slices of renal cortex. These studies provide direct evidence for the production of 1,25-(OH)2D3 and 24,25-(OH)2D3 by the mammalian renal cortex. They also demonstrate that this production may be modulated by dietary calcium, strontium, and vitamin D.

  8. Use of 25-hydroxyvitamin D3 and dietary calcium to improve tenderness of beef from the round of beef cows.

    PubMed

    Carnagey, K M; Huff-Lonergan, E J; Lonergan, S M; Trenkle, A; Horst, R L; Beitz, D C

    2008-07-01

    The objective of this trial was to determine how 25-hydroxyvitamin D(3) (25-OH D(3)) supplementation, altering supplemental dietary calcium, or their combination influence postmortem biochemical and tenderness changes in muscles from the round of mature cows. Twenty-seven Angus cows (3 to 7 yr old) were allotted randomly to 9 pens with 3 cows per pen. Treatments were arranged in a 3 x 3 factorial design with 3 dosages of 25-OH D(3) (0, 250, or 500 mg of 25-OH D(3) administered as a 1-time oral bolus 7 d before slaughter) and 3 percentages of supplemental limestone (0.5, 0.75, and 1.0%) replenished in the diet for 3 d before slaughter and after a 2-wk limestone withdrawal. Plasma samples were obtained during the feeding period. Upon slaughter, adductor, gracilus, pectineus, sartorius, semimembranosus, vastus intermedius, and vastus lateralis muscles were obtained and aged for 1, 3, or 7 d. Calcium concentrations were increased in plasma when 250 or 500 mg of 25-OH D(3) were administered (P D(3) were administered. Concentrations of 25-OH D(3) in meat and in plasma and 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2) D(3)] in plasma were increased when 25-OH D(3) was administered (P D(3) or 1,25-(OH)(2) D(3) in meat or in plasma. Calpastatin activity was affected by treatments only in the gracilus and vastus intermedius muscles (P D(3) has some influence on muscle characteristics known to improve tenderness, but improved tenderness was not observed.

  9. Plasma 25-hydroxyvitamin D(3) concentrations in Hermann's tortoises (Testudo hermanni) exposed to natural sunlight and two artificial ultraviolet radiation sources.

    PubMed

    Selleri, Paolo; Di Girolamo, Nicola

    2012-11-01

    Objective-To determine the effect of various UVB radiation sources on plasma 25-hydroxyvitamin D(3) concentrations in Hermann's tortoises (Testudo hermanni). Animals-18 healthy Hermann's tortoises. Procedures-Tortoises were exposed to sunlight in an outdoor enclosure located in the natural geographic range of Hermann's tortoises (n = 6 tortoises) or a self-ballasted mercury-vapor lamp (6) or fluorescent UVB-emitting lamp (6) in an indoor enclosure for 35 days. Plasma samples were obtained from each tortoise on the first (day 0) and last (day 35) days of the study, and concentrations of 25-hydroxyvitamin D(3) were determined. Amount of UVB radiation in enclosures was measured. Results-Mean ± SD plasma 25-hydroxyvitamin D(3) concentrations for tortoises exposed to the mercury-vapor and fluorescent lamps were significantly lower on day 35 (155.69 ± 80.71 nmol/L and 134.42 ± 51.42 nmol/L, respectively) than they were on day 0 (368.02 ± 119.34 nmol/L and 313.69 ± 109.54 nmol/L, respectively). Mean ± SD plasma 25-hydroxyvitamin D(3) concentration for tortoises exposed to sunlight did not differ significantly between days 0 (387.74 ± 114.56 nmol/L) and 35 (411.51 ± 189.75 nmol/L). Mean day 35 plasma 25-hydroxyvitamin D(3) concentration was significantly higher for tortoises exposed to sunlight versus those exposed to mercury-vapor or fluorescent lamps. Sunlight provided significantly more UVB radiation than did the mercury-vapor or fluorescent lamps. Conclusions and Clinical Relevance-Plasma 25-hydroxyvitamin D(3) concentrations differed between tortoises exposed to sunlight and those exposed to artificial UVB sources. Exposure to sunlight at a latitude similar to that of the natural geographic range is recommended for healthy and calcium-deficient tortoises.

  10. Blood mineral, hormone, and osteocalcin responses of multiparous Jersey cows to an oral dose of 25-hydroxyvitamin D3 or vitamin D3 before parturition.

    PubMed

    Taylor, M S; Knowlton, K F; McGilliard, M L; Seymour, W M; Herbein, J H

    2008-06-01

    Twenty-seven multiparous Jersey cows were randomly assigned to receive an oral bolus containing corn starch (control, CON), corn starch plus 15 mg of 25-hydroxyvitamin D(3) (25-OH), or 15 mg of cholecalciferol (D(3)) at 6 d before expected parturition. Cows were maintained in individual box stalls from 20 d before expected parturition and fed a common diet. Jugular blood samples were collected at -14, -13, -5, -4, -3, -2, -1 d before expected calving, at calving, and at 1, 3, 5, 7, 9, 11, 13, 28, 56, and 84 d postcalving. After calving, cows were housed in 1 pen in a free-stall barn and consumed a common diet. Colorimetric assays were used to analyze Ca, P, and Mg concentrations in serum. Serum concentrations of osteocalcin (OC), an indicator of bone formation, serum 25-hydroxyvitamin D(3), and parathyroid hormone (PTH) were determined in samples obtained from d -5 through d 13. The 9 control multiparous cows and 5 untreated primiparous cows were used to evaluate the effect of parity on the variables that were measured. There was no effect of parity on Ca, PTH, or 25-OH concentration. Compared with second-lactation cows and older cows (>2 lactations), first-lactation cows had greater serum OC (22.3, 32.0, and 48.3 ng/mL, respectively), indicating that younger animals were forming more bone. Blood Ca, P, and Mg decreased near the time of calving and then increased over time. Serum 25-hydroxyvitamin D(3) was greater for cows dosed with 25-OH (119.0 ng/mL) compared with those dosed with D(3) (77.5 ng/mL) or CON (69.3 ng/mL). Cows dosed with 25-OH tended to have lower serum PTH concentration, but treatments did not affect serum Ca, P, or Mg. Serum OC was greater in second-lactation cows compared with cows entering their third or fourth lactation but OC was unaffected by treatment. Although results indicated a 60% increase in serum 25-hydroxyvitamin D(3) due to a single oral dose of 25-OH before calving, the amount administered in this study apparently was not

  11. Simultaneous Quantification of 25-Hydroxyvitamin D3 and 24,25-Dihydroxyvitamin D3 in Rats Shows Strong Correlations between Serum and Brain Tissue Levels.

    PubMed

    Xue, Ying; He, Xin; Li, Huan-De; Deng, Yang; Yan, Miao; Cai, Hua-Lin; Tang, Mi-Mi; Dang, Rui-Li; Jiang, Pei

    2015-01-01

    While vitamin D3 is recognized as a neuroactive steroid affecting both brain development and function, efficient analytical method in determining vitamin D3 metabolites in the brain tissue is still lacking, and the relationship of vitamin D3 status between serum and brain remains elusive. Therefore, we developed a novel analysis method by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to simultaneously quantify the concentrations of 25-hydroxyvitamin D3 (25(OH)D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) in the serum and brain of rats fed with different dose of vitamin D3. We further investigated whether variations of serum vitamin D3 metabolites could affect vitamin D3 metabolite levels in the brain. Serum and brain tissue were analyzed by HPLC-MS/MS with electrospray ionization following derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). The method is highly sensitive, specific, and accurate to quantify 25(OH)D3 and 24,25(OH)2D3 in animal brain tissue. Vitamin D3 metabolites in brain tissue were significantly lower in rats fed with a vitamin D deficiency diet than in rats fed with high vitamin D3 diet. There was also a strong correlation of vitamin D3 metabolites in serum and brain. These results indicate that vitamin D3 status in serum affects bioavailability of vitamin D3 metabolites in the brain. PMID:26713090

  12. Simultaneous Quantification of 25-Hydroxyvitamin D3 and 24,25-Dihydroxyvitamin D3 in Rats Shows Strong Correlations between Serum and Brain Tissue Levels

    PubMed Central

    Xue, Ying; He, Xin; Li, Huan-De; Deng, Yang; Yan, Miao; Cai, Hua-Lin; Tang, Mi-Mi; Dang, Rui-Li; Jiang, Pei

    2015-01-01

    While vitamin D3 is recognized as a neuroactive steroid affecting both brain development and function, efficient analytical method in determining vitamin D3 metabolites in the brain tissue is still lacking, and the relationship of vitamin D3 status between serum and brain remains elusive. Therefore, we developed a novel analysis method by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to simultaneously quantify the concentrations of 25-hydroxyvitamin D3 (25(OH)D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) in the serum and brain of rats fed with different dose of vitamin D3. We further investigated whether variations of serum vitamin D3 metabolites could affect vitamin D3 metabolite levels in the brain. Serum and brain tissue were analyzed by HPLC-MS/MS with electrospray ionization following derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). The method is highly sensitive, specific, and accurate to quantify 25(OH)D3 and 24,25(OH)2D3 in animal brain tissue. Vitamin D3 metabolites in brain tissue were significantly lower in rats fed with a vitamin D deficiency diet than in rats fed with high vitamin D3 diet. There was also a strong correlation of vitamin D3 metabolites in serum and brain. These results indicate that vitamin D3 status in serum affects bioavailability of vitamin D3 metabolites in the brain. PMID:26713090

  13. Summer/winter differences in the serum 25-hydroxyvitamin D3 and parathyroid hormone levels of Japanese women

    NASA Astrophysics Data System (ADS)

    Nakamura, K.; Nashimoto, Mitsue; Yamamoto, Masaharu

    Serum 25-hydroxyvitamin D3 [25(OH)D3] is produced in the skin in response to exposure to ultraviolet radiation, and is a good indicator of vitamin D nutritional status. The aim of this study was to determine summer/winter differences in serum 25(OH)D3 and parathyroid hormone (PTH) in Japanese women and how the summer and winter values are related. The subjects were 122 healthy Japanese women aged 45-81 years (average age: 65.7 years). They were medically examined twice, in September 1997 and February 1999. Serum 25(OH)D3 and intact PTH were determined by high-performance liquid chromatography and a two-site immunoradiometric assay respectively. Lifestyle information was obtained through an interview. The seasonal differences (winter minus summer) in 25(OH)D3 [Δ25(OH)D3] and intact PTH concentrations were -18.8 nmol/l (SD 19.2, P<0.0001) and 0.98pmol/l (SD 1.02, P<0.0001) respectively. The correlation coefficient between summer (x) and winter (y) 25(OH)D3 levels was 0.462 (P<0.0001), with a linearly fitted line of y=0.42x+26.4. This relationship was interpreted as subjects with higher summer 25(OH)D3 values having greater reductions in winter 25(OH)D3 concentrations. There were inter-individual differences in Δ25(OH)D3, although the summer and winter 25(OH)D3 concentrations were well-correlated. Since Δ25(OH)D3 was not associated with any of the lifestyle factors, seasonal differences in the 25(OH)D3 concentrations of an individual appeared to reflect her ability to produce 25(OH)D3 photochemically in the skin. Sun bathing would be a less effective means of attaining adequate vitamin D nutritional status in a person with a small seasonal difference in 25(OH)D3, i.e., one with a low 25(OH)D3 level.

  14. Differential expression of cytokines in response to respiratory syncytial virus infection of calves with high or low circulating 25-hydroxyvitamin D3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deficiency of serum levels of 25-hydroxyvitamin D3 has been related to increased risk of lower respiratory tract infections (LRTI) in children. Respiratory syncytial virus (RSV) is the leading cause of LRTI in infants and young children. The neonatal calf model of RSV infection shares many features ...

  15. Circulating Vitamin D3 and 25-hydroxyvitamin D in Humans: An Important Tool to Define Adequate Nutritional Vitamin D Status

    PubMed Central

    Hollis, Bruce W.; Wagner, Carol L.; Drezner, Mark K.; Binkley, Neil C.

    2007-01-01

    Circulating 25-hydroxyvitamin D [25(OH)D] is generally considered the means by which we define nutritional vitamin D status. There is much debate, however, with respect to what a healthy minimum level of circulation 25(OH)D should be. Recent data using various biomarkers such as intact parathyroid hormone (PTH), intestinal calcium absorption, and skeletal density measurements suggest this minimum level to be 80 nmol (32 ng/mL). Surprisingly, the relationship between circulating vitamin D3 and its metabolic product—25(OH)D3 has not been studied. We investigated this relationship in two separate populations: the first, individuals from Hawaii who received significant sun exposure; the second, subjects from a lactation study who received up to 6,400 IU vitamin D3/day for six months. Results: 1) The relationship between circulating vitamin D3 and 25(OH)D in both groups was not linear, but appeared saturable and controlled; 2) Optimal nutritional vitamin D status appeared to occur when molar ratios of circulating vitamin D3 and 25(OH)D exceeded 0.3; at this point, the Vmax of the 25-hydroxylase appeared to be achieved. This was achieved when circulating 25(OH)D exceeded 100 nmol. We hypothesize that as humans live today, the 25-hydroxylase operates well below its Vmax because of chronic substrate deficiency, namely vitamin D3. When humans are sun (or dietary) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate. Thus, the relationship between circulating vitamin D and 25(OH)D may represent what “normal” vitamin D status should be. PMID:17218096

  16. Exploratory Metabolomics Profiling in the Kainic Acid Rat Model Reveals Depletion of 25-Hydroxyvitamin D3 during Epileptogenesis

    PubMed Central

    Heischmann, Svenja; Quinn, Kevin; Cruickshank-Quinn, Charmion; Liang, Li-Ping; Reisdorph, Rick; Reisdorph, Nichole; Patel, Manisha

    2016-01-01

    Currently, no reliable markers are available to evaluate the epileptogenic potential of a brain injury. The electroencephalogram is the standard method of diagnosis of epilepsy; however, it is not used to predict the risk of developing epilepsy. Biomarkers that indicate an individual’s risk to develop epilepsy, especially those measurable in the periphery are urgently needed. Temporal lobe epilepsy (TLE), the most common form of acquired epilepsy, is characterized by spontaneous recurrent seizures following brain injury and a seizure-free “latent” period. Elucidation of mechanisms at play during epilepsy development (epileptogenesis) in animal models of TLE could enable the identification of predictive biomarkers. Our pilot study using liquid chromatography-mass spectrometry metabolomics analysis revealed changes (p-value ≤ 0.05, ≥1.5-fold change) in lipid, purine, and sterol metabolism in rat plasma and hippocampus during epileptogenesis and chronic epilepsy in the kainic acid model of TLE. Notably, disease development was associated with dysregulation of vitamin D3 metabolism at all stages and plasma 25-hydroxyvitamin D3 depletion in the acute and latent phase of injury-induced epileptogenesis. These data suggest that plasma VD3 metabolites reflect the severity of an epileptogenic insult and that a panel of plasma VD3 metabolites may be able to serve as a marker of epileptogenesis. PMID:27526857

  17. Exploratory Metabolomics Profiling in the Kainic Acid Rat Model Reveals Depletion of 25-Hydroxyvitamin D3 during Epileptogenesis.

    PubMed

    Heischmann, Svenja; Quinn, Kevin; Cruickshank-Quinn, Charmion; Liang, Li-Ping; Reisdorph, Rick; Reisdorph, Nichole; Patel, Manisha

    2016-01-01

    Currently, no reliable markers are available to evaluate the epileptogenic potential of a brain injury. The electroencephalogram is the standard method of diagnosis of epilepsy; however, it is not used to predict the risk of developing epilepsy. Biomarkers that indicate an individual's risk to develop epilepsy, especially those measurable in the periphery are urgently needed. Temporal lobe epilepsy (TLE), the most common form of acquired epilepsy, is characterized by spontaneous recurrent seizures following brain injury and a seizure-free "latent" period. Elucidation of mechanisms at play during epilepsy development (epileptogenesis) in animal models of TLE could enable the identification of predictive biomarkers. Our pilot study using liquid chromatography-mass spectrometry metabolomics analysis revealed changes (p-value ≤ 0.05, ≥1.5-fold change) in lipid, purine, and sterol metabolism in rat plasma and hippocampus during epileptogenesis and chronic epilepsy in the kainic acid model of TLE. Notably, disease development was associated with dysregulation of vitamin D3 metabolism at all stages and plasma 25-hydroxyvitamin D3 depletion in the acute and latent phase of injury-induced epileptogenesis. These data suggest that plasma VD3 metabolites reflect the severity of an epileptogenic insult and that a panel of plasma VD3 metabolites may be able to serve as a marker of epileptogenesis. PMID:27526857

  18. Significance of serum 25-hydroxyvitamin D3 and interleukin-6 levels in immunoglobulin treatment of Kawasaki disease in children

    PubMed Central

    An, Xinjiang; Fu, Mingyu; Tian, Jing; Xue, Ying; Xu, Hui

    2016-01-01

    The aim of the study was to investigate the significance of the level of serum 25-hydroxyvitamin D3 [25-(OH)D3] and interleukin (IL)-6 in serum prior to and after immunoglobulin treatment in children suffering from Kawasaki disease in order to provide a reference for the successful treatment of Kawasaki disease in children. From February, 2013 to February, 2015, 45 patients with Kawasaki disease were enrolled in the observation group. The normal control group comprised 43 healthy volunteers and the feverish control group 46 patients with respiratory infection and fever. Venous blood was collected from each case before and after immunoglobulin treatment and the level of 25-(OH)D3 and IL-6 in the serum were measured using fluorescent quantitative PCR, enzyme-linked immunosorbent assay and western blotting. Before treatment, the level of 25-(OH)D3 in the feverish control group was significantly lower than that of the normal control group, while the level of 25-(OH)D3 in the observation group was significantly higher than that of the normal control group. The level of 25-(OH)D3 in the feverish control group was lower than the IL-6 level in the normal children, but the difference was not statistically significant (P>0.05). The level 25-(OH)D3 in the observation group was significantly higher than the IL-6 level in the normal control group. The serum content of 25-(OH)D3 was significantly higher after the treatment compared to before treatment levels and after treatment IL-6 level was only slightly lower. It was observed that the 25-(OH)D3 level in the observation group was significantly increased after immunoglobulin treatment and this was positively correlated with the effects of the treatment. The IL-6 level had no significant changes after treatment and had little correlation with the treatment effect. The results suggested that 25-(OH)D3 may be involved in the occurrence of Kawasaki disease in children and in the aggravation of the disease to some extent. PMID

  19. Meal conditions affect the absorption of supplemental vitamin D3 but not the plasma 25-hydroxyvitamin D response to supplementation.

    PubMed

    Dawson-Hughes, Bess; Harris, Susan S; Palermo, Nancy J; Ceglia, Lisa; Rasmussen, Helen

    2013-08-01

    It is sometimes assumed that dietary fat is required for vitamin D absorption, although the impact of different amounts of dietary fat on vitamin D absorption is not established. This study was conducted to determine whether the presence of a meal and the fat content of the meal influences vitamin D absorption or the 25-hydroxyvitamin D [25(OH)D] response to supplemental vitamin D3 . Based on earlier studies in rats we postulated that absorption would be greatest in the low-fat meal group. Sixty-two healthy older men and women were randomly assigned to one of three meal groups: no meal, high-fat meal, or low-fat meal; each was given a monthly 50,000 IU vitamin D3 supplement with the test breakfast meal (or after a fast for the no-meal group) and followed for 90 days. Plasma vitamin D3 was measured by liquid chromatography-mass spectroscopy (LC/MS) before and 12 hours after the first dose; plasma 25(OH)D was measured by radioimmunoassay at baseline and after 30 and 90 days. The mean 12-hour increments in vitamin D3 , after adjusting for age and sex, were 200.9 nmol/L in the no-meal group, 207.4 nmol/L in the high-fat meal group, and 241.1 nmol/L in the low-fat meal group (p = 0.038), with the increase in the low-fat group being significantly greater than the increases in the other two groups. However, increments in 25(OH)D levels at 30 and 90 days did not differ significantly in the three groups. We conclude that absorption was increased when a 50,000 IU dose of vitamin D was taken with a low-fat meal, compared with a high-fat meal and no meal, but that the greater absorption did not result in higher plasma 25(OH)D levels in the low-fat meal group.

  20. Novel Mechanism of Negative Regulation of 1,25-Dihydroxyvitamin D3-induced 25-Hydroxyvitamin D3 24-Hydroxylase (Cyp24a1) Transcription

    PubMed Central

    Seth-Vollenweider, Tanya; Joshi, Sneha; Dhawan, Puneet; Sif, Said; Christakos, Sylvia

    2014-01-01

    The SWI/SNF chromatin remodeling complex facilitates gene transcription by remodeling chromatin using the energy of ATP hydrolysis. Recent studies have indicated an interplay between the SWI/SNF complex and protein-arginine methyltransferases (PRMTs). Little is known, however, about the role of SWI/SNF and PRMTs in vitamin D receptor (VDR)-mediated transcription. Using SWI/SNF-defective cells, we demonstrated that Brahma-related gene 1 (BRG1), an ATPase that is a component of the SWI/SNF complex, plays a fundamental role in induction by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) of the transcription of Cyp24a1 encoding the enzyme 25-hydroxyvitamin D3 24-hydroxylase involved in the catabolism of 1,25(OH)2D3. BRG1 was found to associate with CCAAT-enhancer-binding protein (C/EBP) β and cooperate with VDR and C/EBPβ in regulating Cyp24a1 transcription. PRMT5, a type II PRMT that interacts with BRG1, repressed Cyp24a1 transcription and mRNA expression. Our findings indicate the requirement of the C/EBP site for the inhibitory effect of PRMT5 via its methylation of H3R8 and H4R3. These findings indicate that the SWI/SNF complex and PRMT5 may be key factors involved in regulation of 1,25(OH)2D3 catabolism and therefore in the maintenance of calcium homeostasis by vitamin D. These studies also define epigenetic events linked to a novel mechanism of negative regulation of VDR-mediated transcription. PMID:25324546

  1. 25-Hydroxyvitamin D3 1alpha-hydroxylase splice variants in benign and malignant ovarian cell lines and tissue.

    PubMed

    Fischer, Dorothea; Thomé, Marlene; Becker, Steffi; Cordes, Tim; Diedrich, Klaus; Friedrich, Michael; Thill, Marc

    2009-09-01

    Calcitriol is judged to have a positive effect on control of the immune system, cell growth and differentiation and therefore, the prevention of cancer genesis. The aim of this study was to detect any possible differences in the 25-hydroxyvitamin D-1alpha-hydroxylase (1alphaOHase)-expression between benign and malignant ovarian tissue and cell lines. The analysis was conducted quantitatively, by means of nested "touchdown" PCR and Western blot, and qualitatively, with the use of real-time PCR and Western blot. The gene structure was sequenced. Compared to the benign cell line, the malignant cell lines showed a significantly higher expression of 1alphaOHase at the RNA level. A statistically lower expression of the 1alphaOHase protein was found in the malignant tissue. In the malignant cell lines and tissues, divergent bands were detected, which led to various splice variants on sequencing. Their increased expression in malignancy is possibly bound to the reduction of enzyme activity, which may lead to the genesis of ovarian cancer. In the future, preventive and therapeutic activities may result from these findings. PMID:19667158

  2. Effect of 25-hydroxyvitamin D3 on rotavirus replication and gene expressions of RIG-I signalling molecule in porcine rotavirus-infected IPEC-J2 cells.

    PubMed

    Zhao, Ye; Yu, Bing; Mao, Xiangbing; He, Jun; Huang, Zhiqing; Zheng, Ping; Yu, Jie; Han, Guoquan; Liang, Xiaofang; Chen, Daiwen

    2015-01-01

    The study evaluated whether a 25-hydroxyvitamin D3 (25D3) supplementation decreases the replication of rotavirus by the retinoic acid-inducible gene I (RIG-I) signalling pathway in a porcine small intestinal epithelial cell line (IPEC-J2). The results show that IPEC-J2 cells express high baseline levels of 1α-hydroxylase (CYP27B1), which converts inactive 25D3 to the active 1,25-dihydroxyvitamin D3 (1,25D3). Porcine rotavirus (PRV) infection alone resulted in a significant increase in CYP27B1 mRNA, which augmented the production of active vitamin D. Physiological concentrations of 25D3 were found to decrease PRV replication in IPEC-J2 cells. RIG-I plays an important role in the recognition of double-stranded RNA virus by host cells. Upon recognition, RIG-I triggers a series of signalling molecules such as interferon-β (IFN-β) promoter stimulator 1 (IPS-1) leading to the expression of type I interferons (IFN-β). Active 25D3 that was generated by PRV-infected IPEC-J2 cells led to an increased expression of toll-like receptors 3 (TLR3), RIG-I, IPS-1, IFN-β and IFN-stimulated genes 15 (ISG15) with important innate immune functions. Inhibiting CYP27B1 also failed to increase RIG-I, IPS-1, IFN-β and ISG15 mRNA expression. These observations suggest that 25D3 can directly inhibit PRV in IPEC-J2 cells, which requires this active form of vitamin D. The anti-rotavirus effect of 25D3 is mediated at least in part by RIG-I signalling pathways in IPEC-J2 cells.

  3. Availability of 25-hydroxyvitamin D3 to antigen presenting cells controls the balance between regulatory and inflammatory T cell responses

    PubMed Central

    Jeffery, Louisa E.; Wood, Alice M.; Qureshi, Omar S; Hou, Tie Zheng; Gardner, David; Briggs, Zoe; Kaur, Satdip; Raza, Karim; Sansom, David M.

    2012-01-01

    1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, exerts potent effects on several tissues including cells of the immune system, where it affects T cell activation, differentiation and migration. The circulating, inactive form of vitamin D, 25(OH)D3, is generally used as an indication of “vitamin D status”. However, utilization of this precursor depends on its uptake by cells and subsequent conversion by the enzyme 25(OH)D3-1α-hydroxylase (CYP27B1) into active 1,25(OH)2D3. Using human T cells, we now show that addition of inactive 25(OH)D3 is sufficient to alter T cell responses only when dendritic cells (DCs) are present. Mechanistically, CYP27B1 is induced in DCs upon maturation with LPS or upon T cell contact resulting in the generation and release of 1,25(OH)2D3 which subsequently affects T cell responses. In most tissues, vitamin D binding protein (DBP) acts as a carrier to enhance the utilization of vitamin D. However, we show that DBP modulates T cell responses by restricting the availability of inactive 25(OH)D3 to DC. These data indicate that the level of “free” 25(OH)D3 available to DCs determines the inflammatory/regulatory balance of ensuing T cell responses. PMID:23087405

  4. Effects of Dietary Calcium Restriction and Chronic Thyroparathyroidectomy on the Metabolism of [3H]25-Hydroxyvitamin D3 and the Active Transport of Calcium by Rat Intestine

    PubMed Central

    Favus, Murray J.; Walling, Marlin W.; Kimberg, Daniel V.

    1974-01-01

    Previous studies have shown that chronically thyroparathyroidectomized (TPTX) rats, fed a diet with restricted calcium but adequate phosphorus and vitamin D content, have higher levels of intestinal calcium absorption than controls. The results of recent acute experiments have suggested that parathyroid hormone (PTH) may be essential for regulating the renal conversion of 25-hydroxyvitamin D3 (25-OH-D3) to 1,25-dihydroxyvitamin D3 [1,25-(OH)2-D3] in response to dietary calcium deprivation. Since 1,25-(OH)2-D3 is the form of the vitamin thought to be active in the intestine, increases in calcium transport mediated by this metabolite would not be expected to occur in the absence of the parathyroid glands if the preceding model is correct. The present study was undertaken to examine the chronic effects of both dietary calcium restriction and the absence of PTH on the metabolism of [3H]25-OH-D3 and duodenal calcium-active transport in rats given thyroid replacement. These relatively long term studies confirm earlier observations which indicated that the adaptation of calcium absorption to a low calcium intake occurs in both sham-operated and TPTX animals. The present studies also demonstrated that despite reduced levels of 1,25-(OH)2-D3 in the plasma of chronically TPTX animals fed a low calcium diet, the accumulation of this metabolite in at least one target tissue, intestinal mucosa, is identical in both the sham-operated and TPTX groups. A reduced, but continued level of 1,25-(OH)2-D3 production, together with its selective accumulation by intestinal mucosa, probably explains the calcium adaptation which is observed inspite of the chronic absence of the parathyroid glands. PMID:4815079

  5. The association between serum 25-hydroxyvitamin D3 concentration and risk of disease death in men: modification by magnesium intake.

    PubMed

    Mursu, Jaakko; Nurmi, Tarja; Voutilainen, Sari; Tuomainen, Tomi-Pekka; Virtanen, Jyrki K

    2015-04-01

    Low vitamin D status increases the risk of death. Magnesium plays an essential role in vitamin D metabolism and low magnesium intake may predispose to vitamin D deficiency and potentiate the health problems. We investigated whether magnesium intake modifies the serum 25(OH)D3 concentration and its associations with mortality in middle-aged and older men. We included 1892 men aged 42-60 years without cardiovascular disease or cancer at baseline in 1984-1989 from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study. Serum 25(OH)D3 was measured with the high-performance liquid chromatography using coulometric electrode array detection. Magnesium intake was assessed with 4-day food recording. Deaths were ascertained by a computer linkage to the national cause of death register. Deaths due accidents and suicides were excluded. Cox proportional hazards regression models were used to analyze the associations. The multivariate-adjusted hazard ratio (HR) for death in the lowest (<32.1 nmol/L) versus the highest (>49.4 nmol/L) serum 25(OH)D3 tertile was 1.31 (95 % CI 1.07-1.60, Ptrend = 0.01). Stratified by the magnesium intake, the higher risk was observed only in the lower magnesium intake median (<414 mg/day); HR = 1.60 (95 % CI 1.19-2.13, Ptrend = 0.002) in the lowest versus the highest 25(OH)D3 tertile, whereas the corresponding HR = 1.07, 95 % CI 0.75-1.36, Ptrend = 0.63) in the higher magnesium intake median, P for interaction = 0.08. In this cohort of middle-aged and older men low serum 25(OH)D3 concentration was associated with increased risk of death mainly in those with lower magnesium intake.

  6. The Association of Serum 25-Hydroxyvitamin D3 and D2 with Depressive Symptoms in Childhood--A Prospective Cohort Study

    ERIC Educational Resources Information Center

    Tolppanen, Anna-Maija; Sayers, Adrian; Fraser, William D.; Lewis, Glyn; Zammit, Stanley; Lawlor, Debbie A.

    2012-01-01

    Background: Depression in adolescence is common and early onset predicts worse outcome in adulthood. Studies in adults have suggested a link between higher total 25-hydroxyvitamin D [25(OH)D] concentrations and lower risk of depression. Objectives: To investigate (a) the association between serum 25(OH)D[subscript 2] and 25(OH)D[subscript 3]…

  7. Effects of vitamin D2-fortified bread v. supplementation with vitamin D2 or D3 on serum 25-hydroxyvitamin D metabolites: an 8-week randomised-controlled trial in young adult Finnish women.

    PubMed

    Itkonen, Suvi T; Skaffari, Essi; Saaristo, Pilvi; Saarnio, Elisa M; Erkkola, Maijaliisa; Jakobsen, Jette; Cashman, Kevin D; Lamberg-Allardt, Christel

    2016-04-14

    There is a need for food-based solutions for preventing vitamin D deficiency. Vitamin D3 (D3) is mainly used in fortified food products, although the production of vitamin D2 (D2) is more cost-effective, and thus may hold opportunities. We investigated the bioavailability of D2 from UV-irradiated yeast present in bread in an 8-week randomised-controlled trial in healthy 20-37-year-old women (n 33) in Helsinki (60°N) during winter (February-April) 2014. Four study groups were given different study products (placebo pill and regular bread=0 µg D2 or D3/d; D2 supplement and regular bread=25 µg D2/d; D3 supplement and regular bread=25 µg D3/d; and placebo pill and D2-biofortified bread=25 µg D2/d). Serum 25-hydroxyvitamin D2 (S-25(OH)D2) and serum 25-hydroxyvitamin D3 (S-25(OH)D3) concentrations were measured at baseline, midpoint and end point. The mean baseline total serum 25-hydroxyvitamin D (S-25(OH)D=S-25(OH)D2+S-25(OH)D3) concentration was 65·1 nmol/l. In repeated-measures ANCOVA (adjusted for baseline S-25(OH)D as total/D2/D3), D2-bread did not affect total S-25(OH)D (P=0·707) or S-25(OH)D3 (P=0·490), but increased S-25(OH)D2 compared with placebo (P<0·001). However, the D2 supplement was more effective than bread in increasing S-25(OH)D2 (P<0·001). Both D2 and D3 supplementation increased total S-25(OH)D compared with placebo (P=0·030 and P=0·001, respectively), but D2 supplementation resulted in lower S-25(OH)D3 (P<0·001). Thus, D2 from UV-irradiated yeast in bread was not bioavailable in humans. Our results support the evidence that D2 is less potent in increasing total S-25(OH)D concentrations than D3, also indicating a decrease in the percentage contribution of S-25(OH)D3 to the total vitamin D pool. PMID:26864127

  8. Effects of vitamin D2-fortified bread v. supplementation with vitamin D2 or D3 on serum 25-hydroxyvitamin D metabolites: an 8-week randomised-controlled trial in young adult Finnish women.

    PubMed

    Itkonen, Suvi T; Skaffari, Essi; Saaristo, Pilvi; Saarnio, Elisa M; Erkkola, Maijaliisa; Jakobsen, Jette; Cashman, Kevin D; Lamberg-Allardt, Christel

    2016-04-14

    There is a need for food-based solutions for preventing vitamin D deficiency. Vitamin D3 (D3) is mainly used in fortified food products, although the production of vitamin D2 (D2) is more cost-effective, and thus may hold opportunities. We investigated the bioavailability of D2 from UV-irradiated yeast present in bread in an 8-week randomised-controlled trial in healthy 20-37-year-old women (n 33) in Helsinki (60°N) during winter (February-April) 2014. Four study groups were given different study products (placebo pill and regular bread=0 µg D2 or D3/d; D2 supplement and regular bread=25 µg D2/d; D3 supplement and regular bread=25 µg D3/d; and placebo pill and D2-biofortified bread=25 µg D2/d). Serum 25-hydroxyvitamin D2 (S-25(OH)D2) and serum 25-hydroxyvitamin D3 (S-25(OH)D3) concentrations were measured at baseline, midpoint and end point. The mean baseline total serum 25-hydroxyvitamin D (S-25(OH)D=S-25(OH)D2+S-25(OH)D3) concentration was 65·1 nmol/l. In repeated-measures ANCOVA (adjusted for baseline S-25(OH)D as total/D2/D3), D2-bread did not affect total S-25(OH)D (P=0·707) or S-25(OH)D3 (P=0·490), but increased S-25(OH)D2 compared with placebo (P<0·001). However, the D2 supplement was more effective than bread in increasing S-25(OH)D2 (P<0·001). Both D2 and D3 supplementation increased total S-25(OH)D compared with placebo (P=0·030 and P=0·001, respectively), but D2 supplementation resulted in lower S-25(OH)D3 (P<0·001). Thus, D2 from UV-irradiated yeast in bread was not bioavailable in humans. Our results support the evidence that D2 is less potent in increasing total S-25(OH)D concentrations than D3, also indicating a decrease in the percentage contribution of S-25(OH)D3 to the total vitamin D pool.

  9. Photoaffinity labeling of the rat plasma vitamin D binding protein with (26,27-3H)-25-hydroxyvitamin D3 3 beta-(N-(4-azido-2-nitrophenyl)glycinate)

    SciTech Connect

    Ray, R.; Holick, S.A.; Hanafin, N.; Holick, M.F.

    1986-08-26

    It is well recognized that the vitamin D binding protein (DBP) is important for the transport of vitamin D, 25-hydroxyvitamin D (25-OH-D), and its metabolites. In an attempt to better understand the molecular-binding properties of this ubiquitous protein, we designed and synthesized a photoaffinity analogue of 25-OH-D3 and its radiolabeled counterpart. This analogue, 25-hydroxyvitamin D3 3 beta-(N-(4-azido-2-nitrophenyl)glycinate) (25-OH-D3-ANG), was recognized by the rat DBP and was about 10 times less active than 25-OH-D3 in terms of binding. Incubation of (/sup 3/H)25-OH-D3 or (/sup 3/H)25-OH-D3-ANG with rat DBP revealed that both compounds were specifically bound to a protein with a sedimentation coefficient of 4.1 S. Each was displaced with a 500-fold excess of 25-OH-D3. When (/sup 3/H)25-OH-D3-ANG was exposed to UV radiation in the presence of rat DBP followed by the addition of a 500-fold excess of 25-OH-D3, there was no displacement of tritium from the 4.1S peak. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiographic analysis of (/sup 3/H)25-OH-D3-ANG exposed to UV radiation in the presence of rat DBP followed by the addition of a 500-fold excess of 25-OH-D3 revealed one major band with a molecular weight of 52 000. These data provide strong evidence that (/sup 3/H)25-OH-D3-ANG was covalently linked to the rat DBP. This photoaffinity probe should provide a valuable tool for the analysis of the binding site on this transport protein.

  10. A Method for Simultaneous Determination of 25-Hydroxyvitamin D3 and Its 3-Sulfate in Newborn Plasma by LC/ESI-MS/MS after Derivatization with a Proton-Affinitive Cookson-Type Reagent.

    PubMed

    Higashi, Tatsuya; Yokota, Mai; Goto, Ayaka; Komatsu, Kenji; Sugiura, Takahiro; Ogawa, Shoujiro; Satoh, Mamoru; Nomura, Fumio

    2016-01-01

    A method for the simultaneous determination of 25-hydroxyvitamin D3 [25(OH)D3] and its 3-sulfate [25(OH)D3S] in newborn plasma, which is expected to be helpful in the assessment of the vitamin D status, using stable isotope-dilution liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) has been developed and validated. The plasma was pretreated based on the deproteinization and solid-phase extraction, then subjected to derivatization with 4-(4-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD). The derivatization enabled the accurate quantification of 25(OH)D3 without interference from 3-epi-25(OH)D3 and also facilitated the simultaneous determination of the two metabolites by LC/positive ESI-MS/MS. Quantification was based on the selected reaction monitoring with the characteristic fragmentation of the DAPTAD-derivatives during MS/MS. This method was reproducible (intra- and inter-assay relative standard deviations of 7.8% or lower for both metabolites) and accurate (analytical recovery, 95.4-105.6%). The limits of quantification were 1.0 ng/mL and 2.5 ng/mL for 25(OH)D3 and 25(OH)D3S, respectively, when using a 20-μL sample. The developed method was applied to the simultaneous determination of plasma 25(OH)D3 and 25(OH)D3S in newborns; it was recognized that the plasma concentration of 25(OH)D3S is significantly higher than that of 25(OH)D3, and preterm newborns have lower plasma 25(OH)D3S concentrations than full-term newborns. PMID:27656337

  11. A Method for Simultaneous Determination of 25-Hydroxyvitamin D3 and Its 3-Sulfate in Newborn Plasma by LC/ESI-MS/MS after Derivatization with a Proton-Affinitive Cookson-Type Reagent

    PubMed Central

    Higashi, Tatsuya; Yokota, Mai; Goto, Ayaka; Komatsu, Kenji; Sugiura, Takahiro; Ogawa, Shoujiro; Satoh, Mamoru; Nomura, Fumio

    2016-01-01

    A method for the simultaneous determination of 25-hydroxyvitamin D3 [25(OH)D3] and its 3-sulfate [25(OH)D3S] in newborn plasma, which is expected to be helpful in the assessment of the vitamin D status, using stable isotope-dilution liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) has been developed and validated. The plasma was pretreated based on the deproteinization and solid-phase extraction, then subjected to derivatization with 4-(4-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD). The derivatization enabled the accurate quantification of 25(OH)D3 without interference from 3-epi-25(OH)D3 and also facilitated the simultaneous determination of the two metabolites by LC/positive ESI-MS/MS. Quantification was based on the selected reaction monitoring with the characteristic fragmentation of the DAPTAD-derivatives during MS/MS. This method was reproducible (intra- and inter-assay relative standard deviations of 7.8% or lower for both metabolites) and accurate (analytical recovery, 95.4–105.6%). The limits of quantification were 1.0 ng/mL and 2.5 ng/mL for 25(OH)D3 and 25(OH)D3S, respectively, when using a 20-μL sample. The developed method was applied to the simultaneous determination of plasma 25(OH)D3 and 25(OH)D3S in newborns; it was recognized that the plasma concentration of 25(OH)D3S is significantly higher than that of 25(OH)D3, and preterm newborns have lower plasma 25(OH)D3S concentrations than full-term newborns. PMID:27656337

  12. A Method for Simultaneous Determination of 25-Hydroxyvitamin D3 and Its 3-Sulfate in Newborn Plasma by LC/ESI-MS/MS after Derivatization with a Proton-Affinitive Cookson-Type Reagent

    PubMed Central

    Higashi, Tatsuya; Yokota, Mai; Goto, Ayaka; Komatsu, Kenji; Sugiura, Takahiro; Ogawa, Shoujiro; Satoh, Mamoru; Nomura, Fumio

    2016-01-01

    A method for the simultaneous determination of 25-hydroxyvitamin D3 [25(OH)D3] and its 3-sulfate [25(OH)D3S] in newborn plasma, which is expected to be helpful in the assessment of the vitamin D status, using stable isotope-dilution liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) has been developed and validated. The plasma was pretreated based on the deproteinization and solid-phase extraction, then subjected to derivatization with 4-(4-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD). The derivatization enabled the accurate quantification of 25(OH)D3 without interference from 3-epi-25(OH)D3 and also facilitated the simultaneous determination of the two metabolites by LC/positive ESI-MS/MS. Quantification was based on the selected reaction monitoring with the characteristic fragmentation of the DAPTAD-derivatives during MS/MS. This method was reproducible (intra- and inter-assay relative standard deviations of 7.8% or lower for both metabolites) and accurate (analytical recovery, 95.4–105.6%). The limits of quantification were 1.0 ng/mL and 2.5 ng/mL for 25(OH)D3 and 25(OH)D3S, respectively, when using a 20-μL sample. The developed method was applied to the simultaneous determination of plasma 25(OH)D3 and 25(OH)D3S in newborns; it was recognized that the plasma concentration of 25(OH)D3S is significantly higher than that of 25(OH)D3, and preterm newborns have lower plasma 25(OH)D3S concentrations than full-term newborns.

  13. A Method for Simultaneous Determination of 25-Hydroxyvitamin D3 and Its 3-Sulfate in Newborn Plasma by LC/ESI-MS/MS after Derivatization with a Proton-Affinitive Cookson-Type Reagent.

    PubMed

    Higashi, Tatsuya; Yokota, Mai; Goto, Ayaka; Komatsu, Kenji; Sugiura, Takahiro; Ogawa, Shoujiro; Satoh, Mamoru; Nomura, Fumio

    2016-01-01

    A method for the simultaneous determination of 25-hydroxyvitamin D3 [25(OH)D3] and its 3-sulfate [25(OH)D3S] in newborn plasma, which is expected to be helpful in the assessment of the vitamin D status, using stable isotope-dilution liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) has been developed and validated. The plasma was pretreated based on the deproteinization and solid-phase extraction, then subjected to derivatization with 4-(4-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD). The derivatization enabled the accurate quantification of 25(OH)D3 without interference from 3-epi-25(OH)D3 and also facilitated the simultaneous determination of the two metabolites by LC/positive ESI-MS/MS. Quantification was based on the selected reaction monitoring with the characteristic fragmentation of the DAPTAD-derivatives during MS/MS. This method was reproducible (intra- and inter-assay relative standard deviations of 7.8% or lower for both metabolites) and accurate (analytical recovery, 95.4-105.6%). The limits of quantification were 1.0 ng/mL and 2.5 ng/mL for 25(OH)D3 and 25(OH)D3S, respectively, when using a 20-μL sample. The developed method was applied to the simultaneous determination of plasma 25(OH)D3 and 25(OH)D3S in newborns; it was recognized that the plasma concentration of 25(OH)D3S is significantly higher than that of 25(OH)D3, and preterm newborns have lower plasma 25(OH)D3S concentrations than full-term newborns.

  14. The absence of 25-hydroxyvitamin D3-1α-hydroxylase potentiates the suppression of EAE in mice by ultraviolet light.

    PubMed

    Wang, Yanping; Marling, Steve J; Martino, Victoria M; Prahl, Jean M; Deluca, Hector F

    2016-10-01

    Ultraviolet B (UVB) light suppresses the development of multiple sclerosis (MS) in patients and experimental autoimmune encephalomyelitis (EAE) in mice. Although vitamin D3 is produced by ultraviolet light, the suppression of EAE by narrow band UVB (NBUVB) is independent of vitamin D3. However, it is possible that the NBUVB suppression of EAE can be further influenced by 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). We used NBUVB lamps (10KJ/m(2)) to irradiate both wild type (WT) and 1α-hydroxylase knockout mice (CYP27B1 KO) that were then induced to develop EAE. There was a complete elimination of EAE development by NBUVB in the KO mice. On the other hand, the NBUVB treatment of WT mice reduced but did not eliminate the severity or incidence of EAE. This suggests that the presence of 1,25-dihydroxyvitamin D3 actually counteracts the suppressive effect of NBUVB. In support of this concept, cytokines (IFN-γ, IL-10) and chemokine (CCL-5) mRNA in spinal cord were reduced in wild type or eliminated in the KO mice by the NBUVB. Cytokine mRNA levels in the spinal cord correlated with clinical scores in both WT and KO mice.

  15. Effect of feeding 25-hydroxyvitamin D3 with a negative cation-anion difference diet on calcium and vitamin D status of periparturient cows and their calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Holstein cows (>1 gestation) were fed 1 of 3 diets during the last 13 d of gestation (ranged from 22 to 7 d). The Control diet was formulated to provide 18,000 IU/d of vitamin D3 and had a dietary cation-anion difference (DCAD) of 165 mEq/kg (DCAD = Na + K – Cl – S). The second diet (DCAD+D) provi...

  16. Baculovirus-expressed vitamin D-binding protein-macrophage activating factor (DBP-maf) activates osteoclasts and binding of 25-hydroxyvitamin D(3) does not influence this activity.

    PubMed

    Swamy, N; Ghosh, S; Schneider, G B; Ray, R

    2001-01-01

    Vitamin D-binding protein (DBP) is a multi-functional serum protein that is converted to vitamin D-binding protein-macrophage activating factor (DBP-maf) by post-translational modification. DBP-maf is a new cytokine that mediates bone resorption by activating osteoclasts, which are responsible for resorption of bone. Defective osteoclast activation leads to disorders like osteopetrosis, characterized by excessive accumulation of bone mass. Previous studies demonstrated that two nonallelic mutations in the rat with osteopetrosis have independent defects in the cascade involved in the conversion of DBP to DBP-maf. The skeletal defects associated with osteopetrosis are corrected in these mutants with in vivo DBP-maf treatment. This study evaluates the effects of various forms of DBP-maf (native, recombinant, and 25-hydroxyvitamin D(3) bound) on osteoclast function in vitro in order to determine some of the structural requirements of this protein that relate to bone resorbing activities. Osteoclast activity was determined by evaluating pit formation using osteoclasts, isolated from the long bones of newborn rats, incubated on calcium phosphate coated, thin film, Ostologic MultiTest Slides. Incubation of osteoclasts with ex vivo generated native DBP-maf resulted in a dose dependent, statistically significant, activation of the osteoclasts. The activation was similar whether or not the vitamin D binding site of the DBP-maf was occupied. The level of activity in response to DBP-maf was greater than that elicited by optimal doses of other known stimulators (PTH and 1,25(OH(2)D(3)) of osteoclast function. Furthermore, another potent macrophage activating factor, interferon--gamma, had no effect on osteoclast activity. The activated form of a full length recombinant DBP, expressed in E. coli showed no activity in the in vitro assay. Contrary to this finding, baculovirus-expressed recombinant DBP-maf demonstrated significant osteoclast activating activity. The normal

  17. Novel mechanism of negative regulation of 1,25-dihydroxyvitamin D3-induced 25-hydroxyvitamin D3 24-hydroxylase (Cyp24a1) Transcription: epigenetic modification involving cross-talk between protein-arginine methyltransferase 5 and the SWI/SNF complex.

    PubMed

    Seth-Vollenweider, Tanya; Joshi, Sneha; Dhawan, Puneet; Sif, Said; Christakos, Sylvia

    2014-12-01

    The SWI/SNF chromatin remodeling complex facilitates gene transcription by remodeling chromatin using the energy of ATP hydrolysis. Recent studies have indicated an interplay between the SWI/SNF complex and protein-arginine methyltransferases (PRMTs). Little is known, however, about the role of SWI/SNF and PRMTs in vitamin D receptor (VDR)-mediated transcription. Using SWI/SNF-defective cells, we demonstrated that Brahma-related gene 1 (BRG1), an ATPase that is a component of the SWI/SNF complex, plays a fundamental role in induction by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) of the transcription of Cyp24a1 encoding the enzyme 25-hydroxyvitamin D3 24-hydroxylase involved in the catabolism of 1,25(OH)2D3. BRG1 was found to associate with CCAAT-enhancer-binding protein (C/EBP) β and cooperate with VDR and C/EBPβ in regulating Cyp24a1 transcription. PRMT5, a type II PRMT that interacts with BRG1, repressed Cyp24a1 transcription and mRNA expression. Our findings indicate the requirement of the C/EBP site for the inhibitory effect of PRMT5 via its methylation of H3R8 and H4R3. These findings indicate that the SWI/SNF complex and PRMT5 may be key factors involved in regulation of 1,25(OH)2D3 catabolism and therefore in the maintenance of calcium homeostasis by vitamin D. These studies also define epigenetic events linked to a novel mechanism of negative regulation of VDR-mediated transcription.

  18. Performance evaluation of two immunoassays for 25-hydroxyvitamin D

    PubMed Central

    Li, Lusha; Zeng, Qin; Yuan, Jingjing; Xie, Zhongjian

    2016-01-01

    Although immunoassays in measuring 25-hydroxyvitamin D [25(OH)D] have been improved recently, relatively large differences are still seen between results of 25(OH)D measured by immunoassays and by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In the present studies, we compared two immunoassays with LC-MS/MS for measuring 25(OH)D concentrations. Concentrations of 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] in serum samples from 59 healthy subjects were measured by two immunoassays including Siemens ADVIA Centaur Vitamin D Total (Centaur) and Roche Elecsys Vitamin D Total (Elecsys) and LC-MS/MS. To determine the cross reactivity of Elecsys and Centaur toward 25(OH)D2, a dosage of 200,000 IU vitamin D2 was given after first sampling. Serum samples were obtained 30 days later and concentrations of 25(OH)D2 and 25(OH)D3 were measured again. The results showed poor agreement between the immunoassays and LC-MS/MS in 25(OH)D2 and 25(OH)D3 measurements. The percentage of 25(OH)D2 cross-reactivity was 45.3% for Centaur and 41.2% for Elecsys and there was no significant difference between Centaur and Elecsys. In conclusion, Centaur and Elecsys perform unsatisfactorily in measuring 25(OH)D levels, especially for 25(OH)D2 cross-reactivity. Therefore, clinicians need to be aware of the underestimation of vitamin D status when using these immunoassays for measuring individuals supplemented with vitamin D2. PMID:27257343

  19. A Double-Blind, Placebo Controlled, Randomized Trial to Assess the Impact of a Monthly Administration of 50,000 IU of Vitamin D3 for 6 Months on Serum Levels of 25-Hydroxyvitamin D in Healthy Young Adults

    PubMed Central

    Brunel, E.; Schnitzler, M.; Foidart-Dessalle, M.; Souberbielle, J. C.; Cavalier, E.

    2013-01-01

    In this double blind, unicentre, randomized, placebo controlled study, we evaluated the changes in 25-hydroxyvitamin D (25(OH)D) serum levels in 150 young Belgian adults (18–30 years), monthly supplemented with 50,000 IU of vitamin D (VTD) or placebo for 6 months, from November 2010 to May 2011. At T0, 30% of the population presented 25(OH)D serum levels below 20 ng/mL. In the VTD-treated group, mean serum levels increased from 21.2 ± 8.2 to 30.6 ± 8.8 ng/mL (P < 0.001) at T3mo and to 36.0 ± 9.2 ng/mL (P < 0.001) at T6mo. Despite documented VTD intake, no changes in serum levels were, however, observed in 10% of the treated group. In the placebo group, mean 25(OH)D serum levels decreased from 22.8 ± 8.5 to 14.0 ± 6.9 ng/mL at T3mo (P < 0.001) but returned to values not significantly different from those observed at T0 (23.5 ± 8.6 ng/mL) at T6mo. No difference between serum calcium levels was observed between the groups throughout the study. In conclusion, monthly supplementation with 50,000 UI of VTD in winter can warrant serum 25(OH)D levels above 20 ng/mL in 96.2% of those healthy young adults without inducing unacceptably high 25(OH)D concentration. This supplementation is safe and may be proposed without 25(OH)D testing. PMID:24324493

  20. Quantification of physiological levels of vitamin D₃ and 25-hydroxyvitamin D₃ in porcine fat and liver in subgram sample sizes.

    PubMed

    Burild, Anders; Frandsen, Henrik L; Poulsen, Morten; Jakobsen, Jette

    2014-10-01

    Most methods for the quantification of physiological levels of vitamin D3 and 25-hydroxyvitamin D3 are developed for food analysis where the sample size is not usually a critical parameter. In contrast, in life science studies sample sizes are often limited. A very sensitive liquid chromatography with tandem mass spectrometry method was developed to quantify vitamin D3 and 25-hydroxyvitamin D3 simultaneously in porcine tissues. A sample of 0.2-1 g was saponified followed by liquid-liquid extraction and normal-phase solid-phase extraction. The analytes were derivatized with 4-phenyl-1,2,4-triazoline-3,5-dione to improve the ionization efficiency by electrospray ionization. The method was validated in porcine liver and adipose tissue, and the accuracy was determined to be 72-97% for vitamin D3 and 91-124% for 25-hydroxyvitamin D3 . The limit of quantification was <0.1 ng/g, and the precision varied between 1.4 and 16% depending on the level of spiking. The small sample size required for the described method enables quantification of vitamin D3 and 25-hydroxyvitamin D3 in tissues from studies where sample sizes are limited.

  1. The Association between Plasma 25-Hydroxyvitamin D and Subgroups in Age-Related Macular Degeneration: A Cross-Sectional Study

    PubMed Central

    Singh, Amardeep; Falk, Mads Krüger; Subhi, Yousif; Sørensen, Torben Lykke

    2013-01-01

    Objectives To evaluate potential differences in plasma 25-hydroxyvitamin in subtypes of age-related macular degeneration (AMD), and in patients in Clinical Age-Related Maculopathy Staging (CARMS) group 5 with or without subretinal fibrosis. Methods This single-center cross-sectional study included 178 participants during a period of 20 months. Ninety-five patients belonged to CARMS 5; twelve belonged to CARMS 4; twenty-two belonged to CARMS 2 or 3; and 49 individuals did not have AMD (CARMS 1). Following a structured interview, a detailed bilateral retinal examination was performed and participants were allocated to their respective subgroups in accordance with the Clinical Age-Related Maculopathy Staging system. Plasma 25-hydroxyvitamin D2 and D3 were analyzed using liquid chromatography-tandem mass spectrometry. Genomic DNA was extracted from leukocytes and genotyped for single nucleotide polymorphisms (SNPs) in the vitamin D metabolism. Differences in plasma 25-hydroxyvitamin D were determined in the subgroups as well as between patients in CARMS 5 with or without subretinal fibrosis. Results Plasma 25-hydroxyvitamin D was comparable in patients across CARMS groups 1 to 5 (p = 0.83). In CARMS 5, the presence of subretinal fibrosis was associated with significantly lower concentrations of 25-hydroxyvitamin D as compared to the absence of subretinal fibrosis (47.2 versus 75.6 nmol/L, p<0.001). Patients in CARMS 5 with subretinal fibrosis were more likely to have insufficient levels of 25-hydroxyvitamin D compared to patients without subretinal fibrosis (p = 0.006). No association was found between the SNPs rs10877012, rs2228570, rs4588, or rs7041 and AMD subgroups or plasma 25-hydroxyvitamin levels. Conclusions This study suggests that the presence of subretinal fibrosis in patients belonging to CARMS 5 may be associated with a poor vitamin D status. Our observations warrant further investigation into the role of vitamin D in the development of subretinal

  2. The emerging issue of 25-hydroxyvitamin D in foods

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Scientists at the U.S. Department of Agriculture’s (USDA) Agricultural Research Service and the National Institutes of Health’s Office of Dietary Supplements (ODS) write to notify the nutrition community of concerns and needs regarding measurement of vitamin D’s metabolized form, 25-hydroxyvitamin D...

  3. Cross-talk among structural domains of human DBP upon binding 25-hydroxyvitamin D

    PubMed Central

    Ray, Arjun; Swamy, Narasimha; Ray, Rahul

    2007-01-01

    Serum vitamin D-binding protein (DBP) is structurally very similar to serum albumin (ALB); both have three distinct structural domains and high cysteine-content. Yet, functionally they are very different. DBP possesses high affinity for vitamin D metabolites and G-actin, but ALB does not. It has been suggested that there may be cross-talk among the domains so that binding of one ligand may influence the binding of others. In this study we have employed 2-p-toluidinyl-6-sulphonate (TNS), a reporter molecule that fluoresces upon binding to hydrophobic pockets of DBP. We observed that recombinant domain III possesses strong binding for TNS, which is not influenced by 25-hydroxyvitamin D3 (25-OH-D3), yet TNS-fluorescence of the whole protein is quenched by 25-OH-D3. These results provide a direct evidence of cross-talk among the structural domains of DBP. PMID:18035050

  4. Cloning of a functional 25-hydroxyvitamin D-1α-hydroxylase in zebrafish (Danio rerio)

    PubMed Central

    Chun, Rene F.; Blatter, Elizabeth; Elliott, Stephanie; Fitz-Gibbon, Sorel; Rieger, Sandra; Sagasti, Alvaro; Adams, John S.; Hewison, Martin

    2015-01-01

    Activation of precursor 25-hydroxyvitamin D3 (25D) to hormonal 1,25-dihydroxyvitamin D3 (1,25D) is a pivotal step in vitamin D physiology, catalyzed by the enzyme 25-hydroxyvitamin D-1α-hydroxylase (1α-hydroxylase). To establish new models for assessing the physiological importance of the 1α-hydroxylase-25D-axis, we used Danio rerio (zebrafish) to characterize expression and biological activity of the gene for 1α-hydroxylase (cyp27b1). Treatment of day 5 zebrafish larvae with inactive 25D (5-150 nM) or active 1,25D (0.1-10 nM) induced dose responsive expression (15-95 fold) of the vitamin D-target gene cyp24a1 relative to larvae treated with vehicle, suggesting the presence of Cyp27b1 activity. A full-length zebrafish cyp27b1 cDNA was then generated using RACE and RT-PCR methods. Sequencing of the resulting clone revealed an open reading frame encoding a protein of 505 amino acids with 54% identity to human CYP27B1. Transfection of a cyp27b1 expression vector into HKC-8, a human kidney proximal tubular epithelial cell line, enhanced intracrine metabolism of 25D to 1,25D resulting in greater than 2-fold induction of CYP24A1 mRNA expression and a 25-fold increase in 1,25D production compared to empty vector. These data indicate that we have cloned a functional zebrafish CYP27B1, representing a phylogenetically distant branch from mammals of this key enzyme in vitamin D metabolism. Further analysis of cyp27b1 expression and activity in zebrafish may provide new perspectives on the biological importance of 25D metabolism. PMID:25290078

  5. Low 25-Hydroxyvitamin D Levels Are Associated with Infections and Mortality in Patients with Cirrhosis

    PubMed Central

    Finkelmeier, Fabian; Kronenberger, Bernd; Zeuzem, Stefan; Piiper, Albrecht; Waidmann, Oliver

    2015-01-01

    Background & Aims Vitamin D, best known to regulate bone mineralization, has numerous additional roles including regulation inflammatory pathways. Recently, an increased incidence of 25-hydroxyvitamin D3 (25(OH)D3) deficiency has been found in subjects suffering from liver diseases. We here investigated if low vitamin D levels might be associated with prognosis, inflammation and infectious complications in patients with cirrhosis. Methods We performed a prospective cohort study investigating the relation between 25(OH)D3 levels and stages of cirrhosis, mortality and complications of cirrhosis, including infections. Results 251 patients with cirrhosis were enrolled into the present prospective cohort study. 25(OH)D3 levels were quantified by radioimmunoassay from serum samples obtained at study inclusion. The mean follow-up time was 411 ± 397 days with a range of 1-1382 days. 30 (12.0%) patients underwent liver transplantation and 85 (33.8%) individuals died within the study. The mean serum 25(OH)D3 concentration was 8.93 ± 7.1 ng/ml with a range of 1.0 to 46.0 ng/ml. 25(OH)D3 levels differed significantly between Child Pugh scores and showed a negative correlation with the model of end stage liver disease (MELD) score. Patients with decompensated cirrhosis and infectious complications, had significantly lower 25(OH)D3 levels compared to subjects without complications. Low 25(OH)D3 was associated with mortality in uni- as well as multivariate Cox regression models. Conclusions 25(OH)D3 deficiency is associated with advanced liver disease and low 25(OH)D3 levels are an indicator for a poor outcome and are associated with infectious complications. PMID:26121590

  6. A rapid assay for 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D 24-hydroxylase

    SciTech Connect

    Burgos-Trinidad, M.; Brown, A.J.; DeLuca, H.F. )

    1990-10-01

    A rapid method for the measurement of the 24-hydroxylated metabolites of 25-hydroxy(26,27-3H)vitamin D3 and 1,25-dihydroxy(26,27-3H)vitamin D3 has been developed. This measurement has, in turn, made possible a rapid assay for the 24-hydroxylases of the vitamin D system. The assay involves the use of 26,27-3H-labeled 1,25-dihydroxyvitamin D3 or 25-hydroxyvitamin D3 as the substrate and treatment of the enzyme reaction mixture with sodium periodate, which specifically cleaves the 24-hydroxylated products between carbons 24 and 25, releasing tritiated acetone. The acetone is measured after its separation from the labeled substrate by using a reversed-phase cartridge. The results obtained with this assay were validated by comparison with the results obtained with a well-established high-performance liquid chromatography assay. The activity of the enzyme determined by both methods was equal. This assay has been successfully used for the rapid screening of column fractions during purification of the enzyme and in the screening for monoclonal antibodies to the 24-hydroxylase.

  7. First 25-hydroxyvitamin D assay for general chemistry analyzers.

    PubMed

    Saida, Fakhri B; Chen, Xiaoru; Tran, Kiet; Dou, Chao; Yuan, Chong

    2015-03-01

    25-Hydroxyvitamin D [25(OH)D], the predominant circulating form of vitamin D, is an accurate indicator of the general vitamin D status of an individual. Because vitamin D deficiencies have been linked to several pathologies (including osteoporosis and rickets), accurate monitoring of 25(OH)D levels is becoming increasingly important in clinical settings. Current 25(OH)D assays are either chromatographic or immunoassay-based assays. These assays include HPLC, liquid chromatography-tandem mass spectrometry (LC-MS/MS), enzyme-immunosorbent, immunochemiluminescence, immunofluorescence and radioimmunoassay. All these assays use heterogeneous formats that require phase separation and special instrumentations. In this article, we present an overview of these assays and introduce the first homogeneous assay of 25(OH)D for use on general chemistry analyzers. A special emphasis is put on the unique challenges posed by the 25(OH)D analyte. These challenges include a low detection limit, the dissociation of the analyte from its serum transporter and the inactivation of various binding proteins without phase separation steps.

  8. Pediatric 25-Hydroxyvitamin D Concentrations in Neurofibromatosis Type 1

    PubMed Central

    Stevenson, David A.; Viskochil, David H.; Carey, John C.; Sheng, Xiaoming; Murray, Mary; Moyer-Mileur, Laurie; Shelton, Judd; Roberts, William L.; Bunker, Ashley M.; Hanson, Heather; Bauer, Stephanie; D’Astous, Jacques L.

    2011-01-01

    Objective Low 25-hydroxyvitamin D (25OHD) concentrations have been associated with tumors and osteopenia/fractures in adults with neurofibromatosis type 1 (NF1). We report 25OHD concentrations in 109 children with NF1 and 218 age, sex, geographic location, and time-of-year matched controls. Methods Children with NF1 were recruited (n=109; 2–17yr), and clinical data and dual energy x-ray absorptiometry measurements obtained. 25OHD concentrations were measured in subjects and controls. Results More NF1 individuals (50%) were in the 25OHD insufficient/deficient range (<30ng/ml) compared to controls (36%) (p=0.0129). 25OHD concentrations were higher in individuals with neurofibromas after controlling for age (p=0.0393), and negatively associated with whole body subtotal bone mineral density (BMD) z-scores (p=0.0385). Conclusions More children with NF1 had 25OHD concentrations <30ng/ml, potentially due to increased pigmentation and/or decreased sunlight exposure. In contrast to adults, decreased 25OHD concentrations were not associated with neurofibromas, and there was not a positive association of 25OHD with BMD. PMID:21648285

  9. Supplemental vitamin D3 and zilpaterol hydrochloride. I. Effect on performance, carcass traits, tenderness, and vitamin D metabolites of feedlot steers.

    PubMed

    Korn, K T; Lemenager, R P; Claeys, M C; Engstrom, M; Schoonmaker, J P

    2013-07-01

    Angus × Simmental steers (n = 210; initial BW 314 ± 11 kg) were separated into heavy and light BW blocks and allotted evenly by BW to 6 treatments (3 heavy and 2 light pens per treatment) to determine the effect of supplemental vitamin D3: 0 IU (no D), 250,000 IU for 165 d (long-term D), or 5 × 10(6) IU for 10 d (short-term D) on performance, carcass traits, vitamin D metabolites, and meat tenderness in steers fed either 0 (NZ) or 8.38 mg/kg zilpaterol hydrochloride (ZH) daily for 21 d. Placebo or ZH was added to the diet 24 d, and short-term D was added 13 d before slaughter. Vitamin D3, ZH, and placebo were all removed from the diet 3 d before slaughter. Steers fed ZH tended to have improved overall G:F compared with steers not fed ZH (P < 0.09). Overall performance was not affected by long-term D, with or without ZH (P = 0.11) compared with no D, with or without ZH. Short-term D decreased final BW, ADG, and G:F (P = 0.04) compared with no D, when ZH was not fed. Zilpaterol hydrochloride increased HCW, dressing percentage, and LM area (P < 0.01); and decreased fat thickness, yield grade, and marbling (P < 0.03). Carcass traits were not impacted by long-term D without ZH (P > 0.13), but long-term D with ZH decreased percentage KPH (P < 0.02). Compared with no D, short-term D tended to decrease HCW (P < 0.07), decreased fat thickness (P < 0.01), and tended to increase dressing percentage (P < 0.10) when ZH was not fed, yet did not impact carcass traits when ZH was fed (P < 0.13). Feeding ZH tended to decrease (P < 0.09) LM 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The long-term D treatment increased LM vitamin D3 and 25-hydroxyvitamin D3 (25OHD3) 18- and 5-fold, respectively, when ZH was not fed (P < 0.04) and increased LM 25OHD3 by 4-fold when ZH was fed (P < 0.01). Short-term D increased LM vitamin D3 and 25OHD3 by 52- and 9-fold, respectively, when ZH was not fed (P < 0.01), and by 24- and 9-fold, respectively, when ZH was fed (P < 0.01). Also, short-term D

  10. Supplemental vitamin D3 and zilpaterol hydrochloride. I. Effect on performance, carcass traits, tenderness, and vitamin D metabolites of feedlot steers.

    PubMed

    Korn, K T; Lemenager, R P; Claeys, M C; Engstrom, M; Schoonmaker, J P

    2013-07-01

    Angus × Simmental steers (n = 210; initial BW 314 ± 11 kg) were separated into heavy and light BW blocks and allotted evenly by BW to 6 treatments (3 heavy and 2 light pens per treatment) to determine the effect of supplemental vitamin D3: 0 IU (no D), 250,000 IU for 165 d (long-term D), or 5 × 10(6) IU for 10 d (short-term D) on performance, carcass traits, vitamin D metabolites, and meat tenderness in steers fed either 0 (NZ) or 8.38 mg/kg zilpaterol hydrochloride (ZH) daily for 21 d. Placebo or ZH was added to the diet 24 d, and short-term D was added 13 d before slaughter. Vitamin D3, ZH, and placebo were all removed from the diet 3 d before slaughter. Steers fed ZH tended to have improved overall G:F compared with steers not fed ZH (P < 0.09). Overall performance was not affected by long-term D, with or without ZH (P = 0.11) compared with no D, with or without ZH. Short-term D decreased final BW, ADG, and G:F (P = 0.04) compared with no D, when ZH was not fed. Zilpaterol hydrochloride increased HCW, dressing percentage, and LM area (P < 0.01); and decreased fat thickness, yield grade, and marbling (P < 0.03). Carcass traits were not impacted by long-term D without ZH (P > 0.13), but long-term D with ZH decreased percentage KPH (P < 0.02). Compared with no D, short-term D tended to decrease HCW (P < 0.07), decreased fat thickness (P < 0.01), and tended to increase dressing percentage (P < 0.10) when ZH was not fed, yet did not impact carcass traits when ZH was fed (P < 0.13). Feeding ZH tended to decrease (P < 0.09) LM 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The long-term D treatment increased LM vitamin D3 and 25-hydroxyvitamin D3 (25OHD3) 18- and 5-fold, respectively, when ZH was not fed (P < 0.04) and increased LM 25OHD3 by 4-fold when ZH was fed (P < 0.01). Short-term D increased LM vitamin D3 and 25OHD3 by 52- and 9-fold, respectively, when ZH was not fed (P < 0.01), and by 24- and 9-fold, respectively, when ZH was fed (P < 0.01). Also, short-term D

  11. Effect of 25-Hydroxyvitamin D Status on Serological Response to Influenza Vaccine in Prostate Cancer Patients

    PubMed Central

    Chadha, Manpreet K.; Fakih, Marwan; Muindi, Josephia; Tian, Lili; Mashtare, Terry; Johnson, Candace S.; Trump, Donald

    2015-01-01

    BACKGROUND Epidemiologic data suggest that there is an association between vitamin D deficiency and influenza infection. We conducted a prospective influenza vaccination study to determine the influence of vitamin D status on serological response to influenza vaccine in prostate cancer (CaP) patients. METHODS During the 2006–2007 influenza season, CaP patients treated at Roswell Park Cancer Institute were offered vaccination with the trivalent influenza vaccine (Fluzone®, 2006–2007) and sera collected for hemagglutination inhibition (HI) assay titers before and 3 months after vaccination. Response to vaccination was defined as ≥1:40 titer ratio or a fourfold increase in titer at 3 months, against any of the three strains. Serum 25-hydroxyvitamin D (25-D3) levels were measured using DiaSorin 125I radioimmunoassay kits. RESULTS Thirty-five patients with CaP participated in the study. Median baseline 25-D3 level was 44.88 ng/ml (range: 9.16–71.98 ng/ml) Serological response against any of the three strains was noted in 80%. There was a significant effect of baseline 25-D3 level when tested as a continuous variable in relation to serological response (P = 0.0446). All patients in the upper quartile of 25-D3 level responded by mounting a serological response (P = 0.0344). None of the other baseline variables (age, race, chemotherapy status, or white cell count) had an effect on serological response. CONCLUSIONS In this study in CaP patients, a replete vitamin D status was associated with more frequent serological response to influenza vaccine. PMID:20812224

  12. Triple Quadrupole Versus High Resolution Quadrupole-Time-of-Flight Mass Spectrometry for Quantitative LC-MS/MS Analysis of 25-Hydroxyvitamin D in Human Serum

    NASA Astrophysics Data System (ADS)

    Geib, Timon; Sleno, Lekha; Hall, Rabea A.; Stokes, Caroline S.; Volmer, Dietrich A.

    2016-08-01

    We describe a systematic comparison of high and low resolution LC-MS/MS assays for quantification of 25-hydroxyvitamin D3 in human serum. Identical sample preparation, chromatography separations, electrospray ionization sources, precursor ion selection, and ion activation were used; the two assays differed only in the implemented final mass analyzer stage; viz. high resolution quadrupole-quadrupole-time-of-flight (QqTOF) versus low resolution triple quadrupole instruments. The results were assessed against measured concentration levels from a routine clinical chemiluminescence immunoassay. Isobaric interferences prevented the simple use of TOF-MS spectra for extraction of accurate masses and necessitated the application of collision-induced dissociation on the QqTOF platform. The two mass spectrometry assays provided very similar analytical figures of merit, reflecting the lack of relevant isobaric interferences in the MS/MS domain, and were successfully applied to determine the levels of 25-hydroxyvitamin D for patients with chronic liver disease.

  13. Unique form of rickets with low serum 25-hydroxyvitamin D in two normally nourished children.

    PubMed

    Asami, T; Kawasaki, T; Uchiyama, M

    1995-04-01

    We present an unusual type of rickets involving two children: a 2 year old boy and a 15 month old boy, who presented with marked bowing of the lower extremities and bulging of costochondral junctions. Both children had normal growth, with their height and body weight greater than the 50th and 97th percentile for age. Roentgenograms of their extremities showed the typical changes of vitamin D refractory rickets. Serum alkaline phosphatase levels were elevated and serum levels of calcium and phosphate were both within the normal range. No primary cause for the rickets, including nutritional deficiencies, was found in the two patients. Characteristic findings were persistently low serum 25-hydroxyvitamin D (25-OH-D) and normal 1,25-dihydroxyvitamin D (1,25-(OH)2-D). Improvements in clinical and X-ray findings were observed after either oral administration of 1 alpha-(OH)-D3 (9-15 micrograms per day) or massive vitamin D2 therapy (600,000 IU single injection). The low serum levels of 25-OH-D did not increase unless massive vitamin D2 therapy was also given. These two cases represent a unique form of rickets that does not meet the criteria for any type of previously known rickets. PMID:7793252

  14. Determinants of 25-Hydroxyvitamin D Concentrations in Infants and Toddlers

    PubMed Central

    Michel, Hilary; Olabopo, Flora; Wang, Li; Nucci, Anita; Greenspan, Susan L; Rajakumar, Kumaravel

    2015-01-01

    Background Resurgence of rickets and recognition of excessive prevalence of hypovitaminosis D among all age groups in the western hemisphere have refocused attention on vitamin D nutrition. Objective To examine the prevalence of hypovitaminosis D [25-hydroxyvitamin D [25(OH)D] <30ng/mL] and characterize the determinants of 25(OH)D concentrations in 8- to 24-month-old healthy infants and toddlers living in Pittsburgh, Pennsylvania. Methods Serum 25(OH)D concentrations were measured and dietary intake of vitamin D, mode of feeding, summertime sun exposure characteristics, and skin color (sun-reactive skin type and melanin index) were assessed. Results A total of 111 healthy 8- to 24-month-old children (mean age [±SD] 14.4 [±3.5] months; male, 51%; black, 67%) were studied. Serum 25(OH)D concentration was <30 ng/mL in 16% (n=18) of the children. Median (interquartile) 25(OH)D concentration was lower in children who were ≥ 13 months vs. <13 months of age [35 (31, 40.5) vs. 40 (35.8, 44.3) ng/mL, p=0.013]; with sun-reactive skin type IV and V vs. I, II, and III [36 (31, 41) vs. 44 (36.5, 48.5) ng/mL, p=0.001]; and examined during fall/winter vs. spring/summer [35.5 (32.5, 38.5) vs. 39 (32.5, 44) ng/mL, p=0.05]. Age and skin type were significant independent predictors of 25(OH)D. Conclusions Concentrations of 25(OH)D tend to be lower in infants and toddlers during fall/winter, and in children who are older (≥13 months vs. <13 months of age) and have darker skin tone. Benefits of enhancement of 25(OH)D concentrations during fall/winter and in children with higher sun-reactive skin type need further exploration. PMID:26417213

  15. The influence of latitude on the concentration of vitamin D3 and 25-hydroxy-vitamin D3 in Australian red meat.

    PubMed

    Liu, Jerry; Greenfield, Heather; Strobel, Norbert; Fraser, David R

    2013-10-01

    There is little information on the vitamin D content of Australian red meat or on the possible influence of latitude on this content. To determine the content of vitamin D3 and 25-hydroxy-vitamin D3 (25OHD3), lamb and beef were analysed from 34° S with LC-IT-MS. To investigate the possible influence of latitude on vitamin D in meat, the lean meat and fat from five cuts of beef were analysed from 17° S and 41° S. Lamb contained 0.10μg vitamin D3/100g and 0.20μg 25OHD3/100g lean meat, while beef contained 0.12μg vitamin D3 and 0.27μg 25OHD3/100g (lean meat). Latitude had no effect on the vitamin D3 (P=0.21) or 25OHD3 (P=0.29) content of lean beef, but fat from cattle in the 17° S latitude group contained significantly higher (P<0.01) concentrations of vitamin D3 than fat from the 41° S group of cattle.

  16. Serum 25-Hydroxyvitamin D Levels are not Associated with Adverse Outcomes in Clostridium Difficile Infection

    PubMed Central

    Micic, Dejan; Rao, Krishna; Trindade, Bruno Caetano; Walk, Seth T.; Chenoweth, Elizabeth; Jain, Ruchika; Trivedi, Itishree; Santhosh, Kavitha; Young, Vincent B.; Aronoff, David M.

    2015-01-01

    Clostridium difficile infection (CDI) is a significant source of healthcare-associated morbidity and mortality. This study investigated whether serum 25-hydroxyvitamin D is associated with adverse outcomes from CDI. Patients with CDI were prospectively enrolled. Charts were reviewed and serum 25-hydroxyvitamin D was measured. The primary outcome was a composite definition of severe disease: fever (temperature >38°C), acute organ dysfunction, or serum white blood cell count >15,000 cells/µL within 24-48 hours of diagnosis; lack of response to therapy by day 5; and intensive care unit admission; colectomy; or death within 30 days. Sixty-seven patients were included in the final analysis. Mean (±SD) serum 25-hydroxyvitamin D was 26.1 (±18.54) ng/mL. Severe disease, which occurred in 26 (39%) participants, was not associated with serum 25-hydroxyvitamin D [odds ratio (OR) 1.00; 95% confidence interval (CI) 0.96-1.04]. In the adjusted model for severe disease only serum albumin (OR 0.12; 95%CI 0.02-0.64) and diagnosis by detection of stool toxin (OR 5.87; 95%CI 1.09-31.7) remained independent predictors. We conclude that serum 25-hydroxyvitamin D is not associated with the development of severe disease in patients with CDI. PMID:26500740

  17. Serum 25-hydroxyvitamin D is related to indicators of overall physical fitness in healthy postmenopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inadequate vitamin D status is related to increased adiposity, risk of falls, and muscle weakness, particularly in the elderly. We hypothesized that serum 25-hydroxyvitamin D (25(OH) vitamin D) is related to physical fitness indices (androidal fat, whole body lean mass, balance, strength) in healthy...

  18. 25-hydroxyvitamin D levels and juvenile idiopathic arthritis: is there an association with disease activity?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To examine the association between serum levels of 25-hydroxyvitamin D [25(OH)D] and disease activity in juvenile idiopathic arthritis (JIA), to determine the prevalence of vitamin D (VD) deficiency [25(OH)D=19 ng/ml] and insufficiency [25(OH)D 20-29 ng/ml], and to determine factors associated with ...

  19. Plasma 25-hydroxyvitamin D concentration and risk of type 2 diabetes in women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin D may modify risk of type 2 diabetes; however, the association between vitamin D and type 2 diabetes is uncertain. To determine prospectively the association between 25-hydroxyvitamin D (25-OHD) concentration and risk of incident type 2 diabetes, independent of obesity and other known diabet...

  20. Association between subcutaneous white adipose tissue and serum 25-hydroxyvitamin D in overweight and obese adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Cholecalciferol is known to be deposited in human adipose tissue, but the distribution of 25-hydroxyvitamin D (25(OH)D) in adipose tissue is not known. Objectives: To determine whether 25(OH)D is detectable in subcutaneous white adipose tissue (SWAT) in overweight and obese persons an...

  1. Low 25-hydroxyvitamin D levels and cognitive impairment in hemodialysis patients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    25-hydroxyvitamin D (25[OH]D) deficiency and cognitive impairment are both prevalent in hemodialysis patients in the United States. This study tested the hypothesis that 25(OH)D deficiency may be associated with cognitive impairment because of its vasculoprotective, neuroprotective, and immune-modul...

  2. Plasma 25-Hydroxyvitamin D and Progression to Diabetes in Patients at Risk for Diabetes

    PubMed Central

    Pittas, Anastassios G.; Nelson, Jason; Mitri, Joanna; Hillmann, William; Garganta, Cheryl; Nathan, David M.; Hu, Frank B.; Dawson-Hughes, Bess

    2012-01-01

    OBJECTIVE To investigate the association between vitamin D status, assessed by plasma 25-hydroxyvitamin D, and risk of incident diabetes. RESEARCH DESIGN AND METHODS Prospective observational study with a mean follow-up of 2.7 years in the Diabetes Prevention Program (DPP), a multicenter trial comparing different strategies for prevention of diabetes in patients with prediabetes. We assessed the association between plasma 25-hydroxyvitamin D, measured repeatedly during follow-up, and incident diabetes in the combined placebo (n = 1,022) and intensive lifestyle (n = 1,017) randomized arms of the DPP. Variables measured at multiple study time points (25-hydroxyvitamin D, BMI, and physical activity) entered the analyses as time-varying “lagged” covariates, as the mean of the previous and current visits at which diabetes status was assessed. RESULTS After multivariate adjustment, including for the DPP intervention, participants in the highest tertile of 25-hydroxyvitamin D (median concentration, 30.1 ng/mL) had a hazard ratio of 0.72 (95% CI 0.56–0.90) for developing diabetes compared with participants in the lowest tertile (median concentration, 12.8 ng/mL). The association was in the same direction in placebo (0.70; 0.52–0.94) versus lifestyle arm (0.80; 0.54–1.17). CONCLUSIONS Higher plasma 25-hydroxyvitamin D, assessed repeatedly, was associated with lower risk of incident diabetes in high-risk patients, after adjusting for lifestyle interventions (dietary changes, increased physical activity, and weight loss) known to decrease diabetes risk. Because of the observational nature of the study, the potential association between vitamin D and diabetes needs to be confirmed in intervention studies. PMID:22323410

  3. Bone density parathyroid hormone and 25-hydroxyvitamin D concentrations in middle aged women.

    PubMed Central

    Khaw, K. T.; Sneyd, M. J.; Compston, J.

    1992-01-01

    OBJECTIVE--To examine the relation between bone density and indices of calcium metabolism including parathyroid hormone and 25-hydroxyvitamin D concentrations in middle aged women. DESIGN--A cross sectional study. SETTING AND SUBJECTS--138 women volunteers aged 45-65 with no known osteoporosis and unselected for disease status recruited for a dietary assessment study from the community using general practice registers. Volunteer rate was 20%. MAIN OUTCOME MEASURE--Bone mineral density measured with dual energy x ray absorptiometry. RESULTS--Bone density at the lumbar spine and neck and trochanteric regions of the femur was inversely related to serum intact parathyroid hormone concentrations and positively related to serum 25-hydroxyvitamin D concentrations. These associations were independent of possible confounding factors, including age, body mass index, cigarette smoking habit, menopausal status, and use of diuretics and postmenopausal hormone replacement therapy. These associations were apparent throughout the whole distribution of bone density and 25-hydroxyvitamin D and parathyroid hormone concentrations within the normal range, suggesting a physiological relation. CONCLUSIONS--The findings are consistent with the hypothesis that parathyroid hormone and 25-hydroxyvitamin D concentrations influence bone density in middle aged women. Findings from this study together with other work suggest that the role of vitamin D in osteoporosis should not be neglected. The associations with parathyroid hormone also indicate plausible biological mechanisms. The roughly 5-10% difference in bone density between top and bottom tertiles of serum 25-hydroxyvitamin D concentrations, though not large in magnitude, may have considerable public health implications in terms of prevention of osteoporosis and its sequelae, fractures. PMID:1392857

  4. Association between Subcutaneous White Adipose Tissue and Serum 25-Hydroxyvitamin D in Overweight and Obese Adults

    PubMed Central

    Piccolo, Brian D.; Dolnikowski, Gregory; Seyoum, Elias; Thomas, Anthony P.; Gertz, Erik R.; Souza, Elaine C.; Woodhouse, Leslie R.; Newman, John W.; Keim, Nancy L.; Adams, Sean H.; Van Loan, Marta D.

    2013-01-01

    Cholecalciferol is known to be deposited in human adipose tissue, but it is not known whether 25-hydroxyvitamin D (25(OH)D) is found in detectable concentrations. Therefore, our objective was to determine whether 25(OH)D is detectable in subcutaneous white adipose tissue (SWAT) in overweight and obese persons enrolled in a twelve week energy restricted diet. Baseline and post-intervention gluteal SWAT biopsies were collected from 20 subjects participating in a larger clinical weight loss intervention. LC-MS/MS was utilized to determine SWAT 25(OH)D concentrations. Serum 25(OH)D and 1,25(OH)2D were measured by RIA. Body composition was assessed by dual energy x-ray absorptiometry. SWAT 25(OH)D concentrations were 5.8 ± 2.6 nmol/kg tissue and 6.2 ± 2.7 nmol/kg tissue pre- and post-intervention SWAT, respectively. There was a significant positive association between SWAT 25(OH)D concentration and serum 25(OH)D concentration (r = 0.52, P < 0.01). Both SWAT and serum 25(OH)D concentrations did not significantly change after a twelve-week period of energy restriction with approximately 5 kg of fat loss. In conclusion, we have demonstrated our LC-MS/MS method can detect 25(OH)D3 in human subcutaneous fat tissue from overweight and obese individuals and is consistent with previously reported concentrations in swine. Additionally, our findings of no significant changes in SWAT 25(OH)D3 or serum 25(OH)D after a 6% loss of total body weight and 13% reduction in total fat provides the first human evidence that adipose 25(OH)D does not likely contribute to serum 25(OH)D with moderate weight loss; whether this is also the case with larger amounts of weight loss is unknown. Weight loss alone is not sufficient to increase serum 25(OH)D and increases in dietary or dermal biosynthesis of vitamin D appear to be the most critical contributors to in vitamin D status. PMID:24067385

  5. Plasma 25-hydroxyvitamin D, more so than its epimer, has a linear relationship to leaner body composition across infancy in healthy term infants.

    PubMed

    Hazell, Tom J; Gallo, Sina; Berzina, Ilze; Vanstone, Catherine A; Rodd, Celia; Weiler, Hope A

    2014-10-01

    Vitamin D status positively associates with skeletal muscle mass and function in adolescents. The C-3 alpha epimer of 25-hydroxyvitamin D3 (3-epi-25(OH)D3) is high in infants, yet the potential impacts of 25-hydroxyvitamin D3 (25(OH)D3) and 3-epi-25(OH)D3 on skeletal muscle development are largely unexplored. The objective of this study was (i) to explore how the concentrations of 25(OH)D3 and 3-epi-25(OH)D3 track with body composition (lean mass (LM) and fat mass (FM)) and (ii) to determine the association between 25(OH)D3 and 3-epi-25(OH)D3 in infancy. Healthy breastfed infants (n = 132) were followed from 1 to 12 months of age as part of a vitamin D dose-response study (NCT00381914). Anthropometry and diet were assessed. Body composition was measured with dual-energy X-ray absorptiometry. Plasma 25(OH)D3 and 3-epi-25(OH)D3 concentrations were evaluated using liquid chromatography tandem mass spectrometry. Plasma 25(OH)D3 and 3-epi-25(OH)D3 increased from 1 to 3 months of age and decreased thereafter (p < 0.05). Infants with 25(OH)D3 concentrations above 75 nmol/L did not have a higher LM (g or %; p > 0.273) than those below this cutoff. LM was not associated with 25(OH)D3, whereas LM% was positively associated with 25(OH)D3 (β = 0.03; CI: 0.01 to 0.06; p = 0.006), while accounting for sex, weight-for-age Z-score, protein and fat intake, and age. For FM, the variables accounting for a significant amount of the variation were plasma 25(OH)D3 concentration (β = -2.38; CI: -4.35, -0.41; p = 0.019), weight-for-age Z-score, protein and fat intake, and time. In healthy infants, higher vitamin D status associates with leaner body composition, though the effect is smaller in magnitude relative to growth.

  6. Oral vitamin D supplementation at five times the recommended allowance marginally affects serum 25-hydroxyvitamin D concentrations in dogs.

    PubMed

    Young, Lauren R; Backus, Robert C

    2016-01-01

    Little is known regarding optimal vitamin D status in adult dogs. To date no studies on vitamin D supplementation for improving vitamin D status have been reported for adult dogs. The aims of this study were to identify dogs with low vitamin D status and evaluate an oral dosage of cholecalciferol (D3) for effectiveness in increasing vitamin D status. For this, forty-six privately owned dogs were evaluated. Of the dogs, thirty-three (or 71·7 %) had serum 25-hydroxyvitamin D (25(OH)D) concentrations less than 100 ng/ml, a minimum previously suggested for vitamin D sufficiency in dogs. Subsequently, thirteen dogs were enrolled in a supplementation trial. Dogs were given either a D3 supplement (n 7; 2·3 µg/kg(0·75)) or olive oil placebo (n 6) daily with food. Serum concentrations of 25(OH)D were determined at weeks 1, 3 and 6, and at the trial end. Only at the trial end (weeks 9-10) was 25(OH)D significantly greater (P = 0·05) in supplemented v. placebo dogs. Serum concentrations of 24R,25-dihydroxycholecalciferol determined at the trial end were about 40 % of that of 25(OH)D3 and not significantly different between the groups. Concentrations of parathyroid hormone, ionised Ca, P and creatinine measured in initial and final serum samples indicated supplementation caused no toxicity. We conclude that vitamin D3 supplementation at a dosage near the National Research Council recommended safe-upper limit was not effective for rapidly raising serum 25(OH)D concentrations in healthy, adult dogs. Further work is needed in evaluating the metabolism of orally administered D3 in dogs before dosing recommendations can be made. PMID:27547394

  7. Vitamin D delays breast cancer progression in the PyVMT transgenic mouse model: local conversion of the precursor 25(OH)D3 into 1,25(OH)2D3 is safer and more effective than systemic administration of 1,25(OH)2D3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Metabolic activation of 1,25(OH)2D3 occurs at extra renal sites in several organs, including the breast. The purpose of this study was to determine if this local tumoral 25OHD3-1alphahydroxylase expression modulates any or all of the stages of breast tumor progression. For this purpose we used the...

  8. Reduced level of 25-hydroxyvitamin D in chronic/relapsing Alopecia Areata.

    PubMed

    d'Ovidio, Roberto; Vessio, Margherita; d'Ovidio, Francesco Domenico

    2013-04-01

    Current observations link vitamin D deficiency to many autoimmune diseases. There are limited data on vitamin D in Alopecia Areata, an autoimmune disease which in our experience shows seasonality in most of its remitting-relapsing forms. Our results demonstrate the presence of insufficiency of 25-hydroxyvitamin D (25OH-D) in many patients with various clinical forms, correlated with the expected increase of the values of Parathyroid Hormone (PTH). This could suggest the possible clinical use of vitamin D in the management of this frustrating disease.

  9. 25-Hydroxyvitamin D Can Interfere With a Common Assay for 1,25-Dihydroxyvitamin D in Vitamin D Intoxication

    PubMed Central

    Hawkes, Colin P.; Schnellbacher, Sarah; Singh, Ravinder J.

    2015-01-01

    Context: Vitamin D intoxication is characterized by elevated serum 25-hydroxyvitamin D (25(OH)D) and suppressed serum 1,25-dihydroxvitamin D (1,25(OH)2D). We evaluated two adolescents with hypercalcemia due to vitamin D intoxication; both had elevated serum 1,25(OH)2D by Diasorin RIA, but normal serum 1,25(OH)2D concentrations by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Objective: This study aimed to determine the effect of 25(OH)D2 and 25(OH)D3 on 1,25(OH)2D concentration determined using RIA and LC-MS/MS. Methods: Pools of normal serum and an artificial serum matrix were prepared and aliquots were spiked with >99% pure 25(OH)D2 or 25(OH)D3 (50–700 ng/mL). Samples were maintained at 4°C or heated to 56°C, and the concentrations of vitamin D metabolites were measured by LC-MS/MS and Diasorin RIA. Results: Median 1,25(OH)2D increased by 114% with RIA and 21% with LC-MS/MS with addition of 100 ng/mL 25(OH)D3, and 349% (RIA) and 117% (LC-MS/MS) with 700 ng/mL of 25(OH)D3. Each 1-ng/mL increase in 25(OH)D3 increased 1,25(OH)2D by 0.231 pg/mL (RIA) and 0.121 pg/mL (LC-MS/MS). Spiking with 25(OH)D2 led to similar changes. Heat inactivation of serum, and using an artificial serum matrix, were associated with similar effects of 25(OH)D on 1,25(OH)2D assays. Conclusions: Vitamin D intoxication with high serum levels of 25(OH)D2 or 25(OH)D3 can be associated with elevated levels of 1,25(OH)2D due to interference in a commonly used RIA. A similar but attenuated effect also occurs when 1,25(OH)2D is measured using LC-MS/MS but does not seem to be clinically significant. The basis for this effect on the LC-MS/MS assay is presently uncertain. PMID:26120794

  10. Serum 25-hydroxyvitamin D, calcium, and calcium-regulating hormones in preeclamptics and controls during first day postpartum.

    PubMed

    Dalmar, Ahmed; Raff, Hershel; Chauhan, Suneet P; Singh, Maharaj; Siddiqui, Danish S

    2015-02-01

    The evidence for a link between vitamin D and preeclampsia is conflicting. There is a paucity of studies reporting simultaneous 25-hydroxyvitamin D (inactive form) and 1,25-dihydroxyvitamin D (biologically active form). We investigated if levels of serum 25-hydroxyvitamin D, calcium-regulating hormones (1,25-dihydroxyvitamin D, parathyroid hormone), and calcium differ significantly between preeclamptics and controls. On postpartum day one, 98 subjects (44 with preeclampsia, 54 controls) were recruited among women admitted to the postdelivery unit, and their serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, serum calcium, and serum albumin levels were prospectively measured. The majority of participants (70%) had serum 25-hydroxyvitamin D level<20 ng/mL; 53% had <15 ng/mL. Mean serum 25-hydroxyvitamin D level was similar between cases and controls (p=0.50). Mean total serum calcium adjusted for albumin and magnesium was similar between cases and controls (p=0.78). Mean serum 1,25-dihydroxyvitamin D and parathyroid hormone levels were normal, and there were no differences between cases and controls. The only significant differences found between preeclamptic cases and controls were mean body mass index, parity, and season of blood draw. Vitamin D levels did not differ among preeclamptic cases and controls.

  11. Evaluation of Maternal Serum 25-Hydroxyvitamin D, Paraoxonase 1 Levels, and Neutrophil-to-Lymphocyte Ratio in Spontaneous Preterm Birth

    PubMed Central

    Akkar, Ozlem Bozoklu; Sancakdar, Enver; Karakus, Savas; Yildiz, Caglar; Akkar, Ismail; Arslan, Murat; Sahin, Irfan Oguz; Yenicesu, Ayse Gonca Imir; Cetin, Ali

    2016-01-01

    Background The aim of this study was to evaluate the association of maternal serum 25-hydroxyvitamin D, paraoxonase 1, and neutrophil-to-lymphocyte ratio in women having early spontaneous preterm birth without clinical chorioamnionitis. Material/Methods This study was prospectively administered in women referred to our obstetrics service with preterm labor that resulted in preterm birth (n=35) and term labor that ended in term birth (n=44). The maternal serum levels of 25-hydroxyvitamin D and paraoxonase 1 were measured and neutrophil-to-lymphocyte ratio was calculated. Results The 25-hydroxyvitamin D and paraoxonase 1 levels of the preterm group were significantly lower than those of the term group (p<0.05). The neutrophil-to-lymphocyte ratio value of the preterm group was significantly higher than that of the term group (p<0.05). There was a significant but small positive correlation between the serum levels of 25-hydroxyvitamin D and paraoxonase 1 in the preterm group (r=0.35; p=0.021). Conclusions Decreased maternal serum 25-hydroxyvitamin D and paraoxonase 1 levels and increased neutrophil-to-lymphocyte ratio may have a role in the etiology of spontaneous preterm birth. PMID:27072780

  12. Serum 25-hydroxyvitamin D levels in children with recurrent tonsillitis living in Milan.

    PubMed

    Torretta, S; Marchisio, P; Iofrida, E; Capaccio, P; Pignataro, L

    2015-01-01

    Involvement of 25-hydroxyvitamin D in the etiopathogenesis of tonsillar disease in children is still debated; this study assesses possible differences in serum 25-hydroxyvitamin D levels between 309 Caucasian children (58.1% males; mean age 55.7 ± 31.0 months) living in Milan with a history of recurrent tonsillitis (RT) and healthy controls. Mean serum 25(OH)D levels were significantly reduced in the children with a history of RT (22.0 ± 8.7 ng/mL vs 24.6 ± 7.8 ng/mL; p=0.03), and the proportion of children with insufficient or deficient serum 25(OH)D levels was higher in the RT group (81.5% and 6.5% respectively) than in the control group (75.1% and 3.5%) (not significant). The multivariable model created to test the independent association between serum 25(OH)D levels and a history of RT after adjusting for age and season showed that the association was not significant. Our study failed to find any significant reduction in serum 25(OH)D levels after adjustment for age and season in a case series of children with RT in comparison with healthy controls, which suggests that vitamin D does not play a relevant role in the etiology of pediatric tonsillar infections. PMID:26753657

  13. Predictors of Serum 25-Hydroxyvitamin D Concentrations among a Sample of Egyptian Schoolchildren

    PubMed Central

    2016-01-01

    Objective. To assess the level of 25-hydroxyvitamin D status among a sample of Egyptian schoolchildren and to evaluate predictors of deficiency and insufficiency. Subjects and Methods. A cross-sectional study comprising 200 prepubescent schoolchildren aged from 9 to 11 years was performed. A questionnaire including frequency of midday sun exposure, milk intake, physical activity, and level of maternal education was taken. Body mass index (BMI) was calculated; serum 25-hydroxyvitamin D [25(OH)D], serum calcium, phosphorus, and parathyroid hormone were measured. Results. Vitamin D deficiency [serum 25(OH)D < 20 ng/mL] was detected in 11.5% of subjects while its insufficiency (serum 25(OH)D is between 20 and 29.9 ng/mL) was detected in 15%. Results revealed that obesity, low physical activity, low sun exposure, and low maternal education level are significant predictors of insufficiency, though female gender, low maternal education level, and low milk intake are significant predictors of deficiency. Lower serum phosphorus and higher serum parathyroid hormone were significantly associated with both deficiency and insufficiency (p < 0.05). Conclusion. Vitamin D deficiency and insufficiency are common among schoolchildren in Egypt. Food fortification, vitamin D supplementation, and increasing maternal awareness about the importance of physical activity and exposure of their children to ultraviolet light may help to overcome this problem. PMID:26942211

  14. Effects of sunlight on behavior and 25-hydroxyvitamin D levels in two species of Old World fruit bats

    PubMed Central

    Southworth, Lizabeth O.; Holick, Michael F.; Chen, Tai C.; Kunz, Thomas H.

    2013-01-01

    It has long been accepted that most vertebrate animals meet their vitamin D requirements from exposure of skin to UV-B (UV-B) radiation. Many factors affect this endogenous synthesis of vitamin D, including season, latitude, time of day, age, presence of hair, and degree of skin pigmentation. Most bats roost in dark places by day and forage at night, and thus have little or no potential for sunlight exposure. Notwithstanding, some tropical species are diurnal and are known to roost in the canopy of trees where they may be exposed to sunlight for up to 12 h each day. In this study, two species of captive tropical bats (both species are active at night but one, Rousettus aegyptiacus, roosts in caves, tombs, and buildings, whereas the other, Pteropus hypomelanus, roosts in trees) were evaluated for their ability to endogenously synthesize vitamin D. Following timed periods of sunlight exposure, blood plasma was analyzed using a competitive protein binding assay (CPBA) to determine concentrations of 25-hydroxyvitamin D [25(OH)D], the major circulating vitamin D metabolite. The ability to photoconvert provitamin D (7-dehydrocholesterol, 7-DHC) in the sub-tropical winter was determined using sunlight exposed borosilicate samples of 7-DHC in hourly increments. Finally, both species were evaluated in their preference for a roost site by the release of individuals into sunlight or shade in timed trials. Our results support the hypotheses: (1) when exposed to natural sunlight, both species exhibited an ability to endogenously synthesize vitamin D, although significant differences were found between the two, (2) photoconversion of 7-DHC to previtamin D3 is possible during the mid-day hours of a sub-tropical winter day and (3) captive, cave roosting R. aegyptiacus will choose shaded roost sites while captive P. hypomelanus will show no preference for either shade or sun. PMID:24494054

  15. Effects of Vitamin D Supplementation on Serum 25-Hydroxyvitamin D Concentrations in Cirrhotic Patients: A Randomized Controlled Trial

    PubMed Central

    Pilz, Stefan; Putz-Bankuti, Csilla; Gaksch, Martin; Spindelboeck, Walter; Haselberger, Marius; Rainer, Florian; Posch, Andreas; Kreuzer, Philipp; Stojakovic, Tatjana; Stadlbauer, Vanessa; Obermayer-Pietsch, Barbara; Stauber, Rudolf E.

    2016-01-01

    Background: The liver is crucial for 25-hydroxyvitamin D (25(OH)D) metabolism, and vitamin D deficiency is highly prevalent in patients with cirrhosis and predicts adverse outcomes. We aimed to evaluate whether vitamin D supplementation in patients with cirrhosis is effective in increasing 25(OH)D serum concentrations. Secondary outcome measures included liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), and alkaline phosphatase (AP)), albumin, International Normalized Ratio (INR), bilirubin, the liver fibrosis marker hyaluronic acid, and parameters of mineral metabolism including parathyroid hormone (PTH). Methods: This is a double-center, double-blind, placebo-controlled study conducted from December 2013 to May 2014 at the Medical University of Graz, and the hospital Hoergas-Enzenbach, Austria. We enrolled 36 consecutive patients with cirrhosis and 25(OH)D concentrations below 30 ng/mL. Study participants were randomly allocated to receive either 2800 International Units of vitamin D3 per day as oily drops (n = 18) or placebo (n = 18) for 8 weeks. Results: Thirty-three study participants (mean (SD) age: 60 (9) years; 21% females; 25(OH)D: 15.6 (7.4) ng/mL) completed the trial. The mean treatment effect (95% CI) for 25(OH)D was 15.2 (8.0 to 22.4) ng/mL (p < 0.001). There was no significant effect on any secondary outcome. Conclusions: In this randomized controlled trial, vitamin D supplementation increases 25(OH)D serum concentrations, even in cirrhotic patients. PMID:27171112

  16. Serum 25-hydroxyvitamin D assay. Evalution of chromatographic and non-chromatographic procedures.

    PubMed

    Skinner, R K; Wills, M R

    1977-11-01

    A competitive protein binding assay for serum 25-hydroxyvitamin D is described in which normal human serum is used as the source of binding protein. A serum sample is extracted with diethyl ether/methanol and then chromatographed using silica gel. Validation of the method is reported. Silica gel chromatography is compared with LH20 chromatography. The method is also compared with extraction techniques using diethyl ether and ethanol without subsequent chromatography. It is concluded that chromatography with either silica gel or LH20 is essential. The non-chromatographic methods investigated, in addition to giving much higher values than chromatographic methods, did not meet validation requirements with respect to accuracy and behaviour of samples on dilution.

  17. Metabolism of 25-hydroxyvitamin D in copper-laden rat: A model of Wilson's disease

    SciTech Connect

    Carpenter, T.O.; Pendrak, M.L.; Anast, C.S. Yale Univ. School of Medicine, New Haven, CT )

    1988-02-01

    Wilson's disease results in excess tissue accumulation of copper and is often complicated by skeletal and mineral abnormalities. The authors investigated vitamin D metabolism in rats fed a copper-laden diet rendering hepatic copper content comparable with that found in Wilson's disease. Injection of 25-hydroxyvitamin D{sub 3} (25(OH)D{sub 3}) resulted in reduced 1,25--dihydroxyvitamin D (1,25(OH){sub 2}D) levels in copper-intoxicated rats. In vitro 25(OH)D-1{alpha}-hydroxylase activity was impaired in renal mitochondria from copper-intoxicated animals. Activity was also inhibited in mitochondrial from controls when copper was added to incubation media. Impaired conversion of 25(OH)D to 1,25(OH){sub 2}D occurs in copper intoxication and suggests that altered vitamin D metabolism is a potential factor in the development of bone and mineral abnormalities in Wilson's disease.

  18. The Correlation of Plasma 25-Hydroxyvitamin D Deficiency With Risk of Breast Neoplasms: A Systematic Review

    PubMed Central

    Shekarriz-Foumani, Reza; Khodaie, Faezeh

    2016-01-01

    Context Breast cancer has been considered as one of the most common types of cancer among the women worldwide, and patients with breast neoplasms have been reported with high prevalence of low serum 25-hydroxyvitamin D levels. Objectives Our aim was to evaluate the correlation of plasma 25-hydroxyvitamin D deficiency with breast neoplasms risk among women. Data Sources PubMed database was searched with MeSH (medical subject headings) keywords "vitamin D AND breast neoplasms" which was restricted by original articles written only in English and published from January 1, 2014. Study Selection To find the articles that met eligibility criteria, titles and abstracts were examined. Data Extraction This systematic review was conducted according to PRISMA (preferred reporting items for systematic reviews and meta-analyses) statement. Critical appraising of evidence was performed, using the study quality assessment tools of national institutes of health, national heart, lung and blood institute (NHLBI). Results Overall, 76 potential articles were identified and after screening, 13 articles met eligible criteria for inclusion. Definition of low vitamin D levels varied greatly among studies, making comparisons difficult, but most of them have defined deficiency as 25(OH)D < 20 ng/mL. Evidence was mainly of fair quality. Conclusions This study has provided evidence that vitamin D deficiency has been very prevalent in patients with breast neoplasms, more than comparable matched control population, and risk of breast cancer has increased with low vitamin D levels, suggesting the need for high quality studies that assessed the health consequences attributable to vitamin D deficiency employing standard definitions. PMID:27703645

  19. 25-hydroxyvitamin D in obese youth across the spectrum of glucose tolerance from normal to prediabetes to type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to 1) determine if plasma 25-hydroxyvitamin D (25[OH]D) concentrations differ among obese youth with normal glucose tolerance (NGT) versus prediabetes versus type 2 diabetes and 2) assess the relationships between 25(OH)D and in vivo insulin sensitivity and Beta-cell ...

  20. Plasma 25-Hydroxyvitamin D is Associated with Markers of the Insulin Resistance Phenotype in Non-diabetic Adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined the cross-sectional association between plasma 25-hydroxyvitamin D [25(OH)D] and markers of the insulin resistance phenotype. Plasma 25(OH)D concentrations were measured in 808 non-diabetic participants of the Framingham Offspring Study. Outcome measures included fasting and 2-hour pos...

  1. Dietary calcium and serum 25-hydroxyvitamin D status in relation to bone mineral density among US adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A higher calcium intake is still the primary recommendation for the prevention of osteoporosis, while vitamin D deficiency is often not addressed. To study the relative importance of dietary calcium intake and serum 25-hydroxyvitamin D (25(OH)D) status in regard to hip bone mineral density (BMD) in ...

  2. Association between body weight and composition and plasma 25 hydroxyvitamin D level in the diabetes prevention program

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: We examined associations between body weight and plasma 25-hydroxyvitamin D concentration (25OHD) in prediabetes and sought to estimate the impact of adiposity on these associations. Methods: The study was conducted in the placebo (n = 1082) and intensive lifestyle (n = 1079) groups of ...

  3. Studies on the analysis of 25-hydroxyvitamin D{sub 3} by isotope-dilution liquid chromatography–tandem mass spectrometry using enzyme-assisted derivatisation

    SciTech Connect

    Abdel-Khalik, Jonas; Crick, Peter J.; Carter, Graham D.; Makin, Hugh L.; Wang, Yuqin; Griffiths, William J.

    2014-04-11

    Highlights: • New method for the analysis of 25-hydroxyvitamin D{sub 3} exploiting Girard P derivatisation. • Method also applicable to vitamin D{sub 3}, 1α,25- and 24,25-dihydroxyvitamin D{sub 3}. • By modification of the method 3-epi-25-hydroxyvitamin D{sub 3} can also be analysed. - Abstract: The total serum concentration of 25-hydroxyvitamins D (25-hydroxyvitamin D{sub 3} and 25-hydroxyvitamin D{sub 2}) is currently used as an indicator of vitamins D status. Vitamins D insufficiency is claimed to be associated with multiple diseases, thus accurate and precise reference methods for the quantification of 25-hydroxyvitamins D are needed. Here we present a novel enzyme-assisted derivatisation method for the analysis of vitamins D metabolites in adult serum utilising 25-[26,26,26,27,27,27-{sup 2}H{sub 6}]hydroxyvitamin D{sub 3} as the internal standard. Extraction of 25-hydroxyvitamins D from serum is performed with acetonitrile, which is shown to be more efficient than ethanol. Cholesterol oxidase is used to oxidize the 3β-hydroxy group in the vitamins D metabolites followed by derivatisation of the newly formed 3-oxo group with Girard P reagent. 17β-Hydroxysteroid dehydrogenase type 10 is shown to oxidize selectively the 3α-hydroxy group in the 3α-hydroxy epimer of 25-hydroxyvitamin D{sub 3}. Quantification is achieved by isotope-dilution liquid chromatography–tandem mass spectrometry. Recovery experiments for 25-hydroxyvitamin D{sub 3} performed on adult human serum give recovery of 102–106%. Furthermore in addition to 25-hydroxyvitamin D{sub 3}, 24,25-dihydroxyvitamin D{sub 3} and other uncharacterised dihydroxy metabolites, were detected in adult human serum.

  4. Meal conditions affect the absorption of supplemental vitamin D3 but not the plasma 25-hydroxyvitamin D response to supplementation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is sometimes assumed that dietary fat is required for vitamin D absorption, although the impact of different amounts of dietary fat on vitamin D absorption is not established. This study was conducted to determine whether the presence of a meal and the fat content of the meal influences vitamin D...

  5. Serum 25-hydroxyvitamin D concentrations in dogs - correlation with health and cancer risk.

    PubMed

    Selting, K A; Sharp, C R; Ringold, R; Thamm, D H; Backus, R

    2016-09-01

    25-hydroxyvitamin D (25(OH)D) is important in bone health as well as many diseases including cancer. Supplementation may increase responsiveness of cancer cells to chemotherapy. Serum 25(OH)D, intact parathyroid hormone (iPTH) and canine C-reactive protein (c-CRP) were measured in healthy dogs and dogs with haemoabdomen. Regression analysis determined optimal 25(OH)D concentrations. In healthy dogs (n = 282), mean iPTH concentrations correlated inversely (r(2) = 0.88, P < 0.001) to 25(OH)D concentrations. Variation in both iPTH and c-CRP plateaued at 25(OH)D concentrations of 100-120 ng mL(-1) . Haemoabdomen dogs (n = 63, 43 malignant and 20 benign) had 25(OH)D concentrations ranging from 19.4 to >150 ng mL(-1) . Relative risk of cancer increased with decreasing 25(OH)D concentrations [RR = 3.9 for 25(OH)D below 40 ng mL(-1) (P = 0.0001)]. Serum 25(OH)D concentrations in dogs vary widely, and are influenced by dietary VitD content. Serum vitD measurement can identify dogs for which supplementation may improve health and response to cancer therapy.

  6. Vitamin D and 25-hydroxyvitamin D determination in meats by LC-IT-MS.

    PubMed

    Strobel, Norbert; Buddhadasa, Saman; Adorno, Paul; Stockham, Katherine; Greenfield, Heather

    2013-06-01

    This paper reports a method for the rapid, sensitive and simultaneous analysis of vitamin D (Vit D) and 25-hydroxyvitamin D (25OH-Vit D) in meats. Samples were saponified and underwent solid phase extraction with analysis by normal phase liquid chromatography (LC) with ion trap mass spectroscopy (IT-MS), using positive polarity atmospheric pressure chemical ionisation (APCI). Limits of detection (LOD) and quantification (LOQ) for Vit D and 25OH-Vit D were 0.03 and 0.05 μg/100g respectively. Deuterium labelled Vit D and 25OH-Vit D internal standards were added as surrogates prior to saponification, correcting for extraction inefficiencies and potential MS matrix enhancement or suppression effects. Recoveries using internal/surrogate standard correction ranged from 80% to 100% for all vitamers. Measurement uncertainty ranged from 6% to 15% for all vitamers in this method. This process required only 7.5 g of sample per extraction and a batch of 28 extractions could be completed in six hours.

  7. Cord Blood 25-hydroxyvitamin D and Fetal Growth in the China-Anhui Birth Cohort Study.

    PubMed

    Zhu, Peng; Tong, Shi-lu; Hu, Wen-biao; Hao, Jia-hu; Tao, Rui-xue; Huang, Kun; Mou, Zhe; Zhou, Qi-fan; Jiang, Xiao-min; Tao, Fang-biao

    2015-01-01

    We determined the association of cord blood 25-hydroxyvitamin D [25(OH)D] with birth weight and the risk of small for gestational age (SGA). As part of the China-Anhui Birth Cohort (C-ABC) study, we measured cord blood levels of 25(OH)D in 1491 neonates in Hefei, China. The data on maternal sociodemographic characteristics, health status, lifestyle, birth outcomes were prospectively collected. Multiple regression models were used to estimate the association of 25(OH)D levels with birth weight and the risk of SGA. Compared with neonates in the lowest decile of cord blood 25(OH)D levels, neonates in four deciles (the fourth, fifth, sixth and seventh deciles) had significantly increased birth weight and decreased risk of SGA. Multiple linear regression models showed that per 10 nmol/L increase in cord blood 25(OH)D, birth weight increased by 61.0 g (95% CI: 31.9, 89.9) at concentrations less than 40 nmol/L, and then decreased by 68.5 g (95% CI: -110.5, -26.6) at concentrations from 40 to 70 nmol/L. This study provides the first epidemiological evidence that there was an inverted U shaped relationship between neonatal vitamin D status and fetal growth, and the risk of SGA reduced at moderate concentration. PMID:26450157

  8. Altered mineral metabolism in glucocorticoid-induced osteopenia. Effect of 25-hydroxyvitamin D administration.

    PubMed Central

    Hahn, T J; Halstead, L R; Teitelbaum, S L; Hahn, B H

    1979-01-01

    Parameters of mineral and bone metabolism were studied in 17 patients treated chronically with supraphysiologic doses of glucocorticoids. When compared to 15 matched normal subjects, the patient group exhibited similar serum 25-hydroxyvitamin D (25-OHD) levels, decreased intestinal 47Ca absorption, increased serum immunoreactive parathyroid hormone, and decreased forearm bone mass. Iliac crest bone biopsies revealed a decreased bone formation rate and increased osteoclast number. Treatment with 25-OHD (mean dose 4.03 micrograms/d) and calcium (500 mg/d) in nine patients produced a 46% increase in 47Ca absorption (P less than 0.001) and a 54% decrease in serum immunoreactive parathyroid hormone (P less than 0.001) by 3 mo. In addition, by 12 mo the treatment group exhibited (a) a 13.2 +/- 5.1% increase in metaphyseal (P less than 0.001) and a 2.1 +/- 0.4% increase in diaphyseal (P less than 0.05) forearm bone mass, and (b) significant decreases in cortical and endosteal osteoclast number. Biochemical and bone mass changes persisted through 18 mo. No significant changes in any parameter occurred in eight control patients administered calcium 100 mg/d. It is concluded that treatment with 25-OHD and calcium can significantly improve parameters of mineral and bone metabolism in patients with glucocorticoid-induced osteopenia. PMID:457875

  9. A prospective study of plasma 25-hydroxyvitamin D concentration and prostate cancer risk.

    PubMed

    Deschasaux, Mélanie; Souberbielle, Jean-Claude; Latino-Martel, Paule; Sutton, Angela; Charnaux, Nathalie; Druesne-Pecollo, Nathalie; Galan, Pilar; Hercberg, Serge; Le Clerc, Sigrid; Kesse-Guyot, Emmanuelle; Ezzedine, Khaled; Touvier, Mathilde

    2016-01-28

    Mechanistic hypotheses suggest that vitamin D and the closely related parathyroid hormone (PTH) may be involved in prostate carcinogenesis. However, epidemiological evidence is lacking for PTH and inconsistent for vitamin D. Our objectives were to prospectively investigate the association between vitamin D status, vitamin D-related gene polymorphisms, PTH and prostate cancer risk. A total of 129 cases diagnosed within the Supplémentation en Vitamines et Minéraux Antioxydants cohort were included in a nested case-control study and matched to 167 controls (13 years of follow-up). 25-Hydroxyvitamin D (25(OH)D) and PTH concentrations were assessed from baseline plasma samples. Conditional logistic regression models were computed. Higher 25(OH)D concentration was associated with decreased risk of prostate cancer (ORQ4 v. Q1 0·30; 95 % CI 0·12, 0·77; P trend=0·007). PTH concentration was not associated with prostate cancer risk (P trend=0·4) neither did the studied vitamin D-related gene polymorphisms. In this prospective study, prostate cancer risk was inversely associated with 25(OH)D concentration but not with PTH concentration. These results bring a new contribution to the understanding of the relationship between vitamin D and prostate cancer, which deserves further investigation. PMID:26568368

  10. Low levels of serum 25-hydroxyvitamin D and risk of metabolic syndrome in China

    PubMed Central

    Lu, Yanhui; Liu, Minyan; Pei, Yu; Li, Jian; Tian, Hui; Cheng, Xiaoling; Fang, Fusheng; Sun, Banruo; Xiao, Haiying; Li, Nan; Miao, Xinyu; Li, Chunlin

    2015-01-01

    Recent evidence indicates the potential role of vitamin D in the prevention of Metabolic syndrome (MetSyn). This is an analytical cross sectional study. A total of 3275 subjects were investigated. 25-hydroxyvitamin D(25[OH]D) was detected by electrochemiluminescence immunoassay (ECLIA) technology. Metabolic syndrome was defined according to the definition of International Diabetes Federation (IDF). Among the participants, the prevalence of the MetSyn was 6.0%. The prevalence of vitamin D deficiency and insufficiency was 50.1% and 25.0% respectively. Subjects with MetSyn presented with significantly lower 25(OH)Vit D serum levels compared with non-MetSyn group. The results shows that vitamin D deficiency is common in Chinese adults, and subjects with lower serum 25(OH)D have a higher risk of the MetSyn. The cut-off value of serum 25(OH)D that reflected MetSyn in Chinese adluts was 15.655 ng/mL. PMID:26550327

  11. 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services

    PubMed Central

    Buell, J S.; Dawson-Hughes, B; Scott, T M.; Weiner, D E.; Dallal, G E.; Qui, W Q.; Bergethon, P; Rosenberg, I H.; Folstein, M F.; Patz, S; Bhadelia, R A.; Tucker, K L.

    2010-01-01

    Background: Vitamin D deficiency has potential adverse effects on neurocognitive health and subcortical function. However, no studies have examined the association between vitamin D status, dementia, and cranial MRI indicators of cerebrovascular disease (CVD). Methods: Cross-sectional investigation of 25-hydroxyvitamin D [25(OH)D], dementia, and MRI measures of CVD in elders receiving home care (aged 65–99 years) from 2003 to 2007. Results: Among 318 participants, the mean age was 73.5 ± 8.1 years, 231 (72.6%) were women, and 109 (34.3%) were black. 25(OH)D concentrations were deficient (<10 ng/mL) in 14.5% and insufficient (10–20 ng/mL) in 44.3% of participants. There were 76 participants (23.9%) with dementia, 41 of which were classified as probable AD. Mean 25(OH)D concentrations were lower in subjects with dementia (16.8 vs 20.0 ng/mL, p < 0.01). There was a higher prevalence of dementia among participants with 25(OH)D insufficiency (≤20 ng/mL) (30.5% vs 14.5%, p < 0.01). 25(OH)D deficiency was associated with increased white matter hyperintensity volume (4.9 vs 2.9 mL, p < 0.01), grade (3.0 vs 2.2, p = 0.04), and prevalence of large vessel infarcts (10.1% vs 6.9%, p < 0.01). After adjustment for age, race, sex, body mass index, and education, 25(OH)D insufficiency (≤20 ng/mL) was associated with more than twice the odds of all-cause dementia (odds ratio [OR] = 2.3, 95% confidence interval [CI] 1.2–4.2), Alzheimer disease (OR = 2.5, 95% CI 1.1–6.1), and stroke (with and without dementia symptoms) (OR = 2.0, 95% CI 1.0–4.0). Conclusions: Vitamin D insufficiency and deficiency was associated with all-cause dementia, Alzheimer disease, stroke (with and without dementia symptoms), and MRI indicators of cerebrovascular disease. These findings suggest a potential vasculoprotective role of vitamin D. GLOSSARY 25(OH)D = 25-hydroxyvitamin D; AIREN = Association Internationale pour la Recherché et l'Enseignement en Neurosciences; BMI = body mass index; CI

  12. Circulating 25-Hydroxyvitamin D, Vitamin D Binding Protein, and Risk of Prostate Cancer

    PubMed Central

    Weinstein, Stephanie J.; Mondul, Alison M.; Kopp, William; Rager, Helen; Virtamo, Jarmo; Albanes, Demetrius

    2012-01-01

    We recently reported a significant positive association between 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, and prostate cancer risk. To further elucidate this association, we examined the influence of vitamin D binding protein (DBP), the primary transporter of vitamin D compounds in the circulation. Prediagnostic serum concentrations of DBP were assayed for 950 cases and 964 matched controls with existing 25(OH)D measurements within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), and statistical tests were two-sided. Serum DBP modified the association between serum 25(OH)D and prostate cancer, with higher risk for elevated 25(OH)D levels observed primarily among men having DBP concentrations above the median (OR=1.81, 95% CI 1.18–2.79 for highest vs. lowest quintile, p-trend = 0.001) compared to those with DBP below the median (OR=1.22, 95% CI 0.81–1.84, p-trend 0.97; p-interaction = 0.04). Serum DBP was not associated with prostate cancer risk overall (OR=0.96, 95% CI 0.70–1.33 for highest vs. lowest quintile); however, high serum DBP was associated with significantly decreased risk of prostate cancer in men with lower (

  13. Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects.

    PubMed

    Bellia, Alfonso; Garcovich, Caterina; D'Adamo, Monica; Lombardo, Mauro; Tesauro, Manfredi; Donadel, Giulia; Gentileschi, Paolo; Lauro, Davide; Federici, Massimo; Lauro, Renato; Sbraccia, Paolo

    2013-02-01

    Obesity is frequently characterized by a reduced vitamin D bioavailability, as well as insulin-resistance and a chronic inflammatory response. We tested the hypothesis of an independent relationship between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and several circulating inflammatory markers in a cohort of severely obese individuals. Cross-sectional study was carried out among obese patients undergoing a clinical evaluation before bariatric surgery in our University Hospital. Serum 25(OH)D, fasting and post load glucose and insulin, high-sensitive C-reactive protein (hs CRP), fibrinogen, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin and lipid profile were collected. Insulin-resistance was assessed by insulin sensitivity index (ISI). Total body fat (FAT kg), total percent body fat (FAT%) and truncal fat mass (TrFAT) were assessed with dual-energy X-ray absorptiometry. A total of 147 obese subjects (89 women, 37.8 ± 7.1 years) with mean body mass index (BMI) of 43.6 ± 4.3 kg/m(2) were enrolled. Patients in the lowest tertile of 25(OH)D were significantly more obese with a higher amount of TrFAT, more insulin-resistant, and had higher levels of fasting and post-challenge glucose (p < 0.05 for all). In a multivariate regression analysis, serum 25(OH)D was inversely related to significant levels of hs CRP, IL-6 and TNF-α after accounting for age, gender, season of recruitment, BMI, FAT kg and TrFAT (p < 0.01 for all). In extremely obese subjects, 25(OH)D serum concentrations are inversely associated with several biomarkers of systemic inflammation, regardless of the total quantity of fat mass. PMID:21437585

  14. Low serum concentrations of 25-hydroxyvitamin D in children and adolescents with systemic lupus erythematosus

    PubMed Central

    Peracchi, O.A.B.; Terreri, M.T.R.A.; Munekata, R.V.; Len, C.A.; Sarni, R.O.S.; Lazaretti-Castro, M.; Hilário, M.O.E.

    2014-01-01

    We evaluated the concentrations of 25-hydroxyvitamin D [25(OH)D] in children and adolescents with juvenile systemic lupus erythematosus (JSLE) and associated them with disease duration and activity, use of medication (chloroquine and glucocorticoids), vitamin D intake, calcium and alkaline phosphatase levels, and bone mineral density. Thirty patients with JSLE were evaluated and compared to 30 healthy individuals, who were age and gender matched. Assessment was performed of clinical status, disease activity, anthropometry, laboratory markers, and bone mineral density. The 30 patients included 25 (83.3%) females and 16 (53.3%) Caucasians, with a mean age of 13.7 years. The mean age at diagnosis was 10.5 years and mean disease duration was 3.4 years. Mean levels of calcium, albumin, and alkaline phosphatase were significantly lower in patients with JSLE compared with controls (P<0.001, P=0.006, and P<0.001, respectively). Twenty-nine patients (97%) and 23 controls (77%) had 25(OH)D concentrations lower than 32 ng/mL, with significant differences between them (P<0.001). Fifteen patients (50%) had vitamin D levels <20 ng/mL and 14 had vitamin D levels between 20 and 32 ng/mL. However, these values were not associated with greater disease activity, higher levels of parathormone, medication intake, or bone mineral density. Vitamin D concentrations were similar with regard to ethnic group, body mass index, height for age, and pubertal stage. Significantly more frequently than in controls, we observed insufficient serum concentrations of 25(OH)D in patients with JSLE; however, we did not observe any association with disease activity, higher levels of parathormone, lower levels of alkaline phosphatase, use of medications, or bone mineral density alterations. PMID:25055165

  15. Higher serum 25-hydroxyvitamin D concentrations are related to a reduced risk of depression.

    PubMed

    Jääskeläinen, Tuija; Knekt, Paul; Suvisaari, Jaana; Männistö, Satu; Partonen, Timo; Sääksjärvi, Katri; Kaartinen, Niina E; Kanerva, Noora; Lindfors, Olavi

    2015-05-14

    Vitamin D has been suggested to protect against depression, but epidemiological evidence is scarce. The present study investigated the relationship of serum 25-hydroxyvitamin D (25(OH)D) with the prevalence of depressive and anxiety disorders. The study population consisted of a representative sample of Finnish men and women aged 30-79 years from the Health 2000 Survey. The sample included 5371 individuals, of which 354 were diagnosed with depressive disorder and 222 with anxiety disorder. Serum 25(OH)D concentration was determined from frozen samples. In a cross-sectional study, a total of four indicators of depression and one indicator of anxiety were used as dependent variables. Serum 25(OH)D was the risk factor of interest, and logistic models used further included sociodemographic and lifestyle variables as well as indicators of metabolic health as confounding and/or effect-modifying factors. The population attributable fraction (PAF) was estimated. Individuals with higher serum 25(OH)D concentrations showed a reduced risk of depression. The relative odds between the highest and lowest quartiles was 0.65 (95% CI 0.46, 0.93; P for trend = 0.006) after adjustment for sociodemographic, lifestyle and metabolic factors. Higher serum 25(OH)D concentrations were associated with a lower prevalence of depressive disorder especially among men, younger, divorced and those who had an unhealthy lifestyle or suffered from the metabolic syndrome. The PAF was estimated to be 19% for depression when serum 25(OH)D concentration was at least 50 nmol/l. These results support the hypothesis that higher serum 25(OH)D concentrations protect against depression even after adjustment for a large number of sociodemographic, lifestyle and metabolic factors. Large-scale prospective studies are needed to confirm this finding.

  16. 25-Hydroxyvitamin D and TSH as Risk Factors or Prognostic Markers in Thyroid Carcinoma

    PubMed Central

    Danilovic, Debora Lucia Seguro; Ferraz-de-Souza, Bruno; Fabri, Amanda Wictky; Santana, Nathalie Oliveira; Kulcsar, Marco Aurelio; Cernea, Claudio Roberto; Marui, Suemi; Hoff, Ana Oliveira

    2016-01-01

    Objective The increasing incidence of thyroid nodules demands identification of risk factors for malignant disease. Several studies suggested the association of higher TSH levels with cancer, but influence of 25-hydroxyvitamin D (25OHD) is controversial. This study aimed to identify the relationship of thyroid cancer with higher TSH levels and hypovitaminosis D and to evaluate their influence on prognostic characteristics of papillary thyroid carcinomas (PTC). Methods We retrospectively evaluated 433 patients submitted to thyroidectomy for thyroid nodules. Patients were categorized according to quartiles of TSH and 25OHD levels. Clinicopathological features were analyzed. Results Subjects with thyroid carcinomas were more frequently male and younger compared to those with benign disease. Their median TSH levels were higher and adjusted odds-ratio (OR) for cancer in the highest-quartile of TSH (> 2.4 mUI/mL) was 2.36 (1.36–4.09). Although vitamin D deficiency/insufficiency was prevalent in our cohort (84%), no significant differences in 25OHD levels or quartile distribution were observed between benign and malignant cases. Among 187 patients with PTC, analyses of prognostic features revealed increased risk of lymph nodes metastases for subjects with highest-quartile TSH levels (OR = 3.7, p = 0.029). Decreased 25OHD levels were not overtly associated with poor prognosis in PTC. Conclusions In this cross-sectional cohort, higher TSH levels increased the risk of cancer in thyroid nodules and influenced its prognosis, particularly favoring lymph nodes metastases. On the other hand, no association was found between 25OHD levels and thyroid carcinoma risk or prognosis, suggesting that serum 25OHD determination may not contribute to risk assessment workup of thyroid nodules. PMID:27737011

  17. Low serum concentrations of 25-hydroxyvitamin D in children and adolescents with systemic lupus erythematosus.

    PubMed

    Peracchi, O A B; Terreri, M T R A; Munekata, R V; Len, C A; Sarni, R O S; Lazaretti-Castro, M; Hilário, M O E

    2014-08-01

    We evaluated the concentrations of 25-hydroxyvitamin D [25(OH)D] in children and adolescents with juvenile systemic lupus erythematosus (JSLE) and associated them with disease duration and activity, use of medication (chloroquine and glucocorticoids), vitamin D intake, calcium and alkaline phosphatase levels, and bone mineral density. Thirty patients with JSLE were evaluated and compared to 30 healthy individuals, who were age and gender matched. Assessment was performed of clinical status, disease activity, anthropometry, laboratory markers, and bone mineral density. The 30 patients included 25 (83.3%) females and 16 (53.3%) Caucasians, with a mean age of 13.7 years. The mean age at diagnosis was 10.5 years and mean disease duration was 3.4 years. Mean levels of calcium, albumin, and alkaline phosphatase were significantly lower in patients with JSLE compared with controls (P<0.001, P=0.006, and P<0.001, respectively). Twenty-nine patients (97%) and 23 controls (77%) had 25(OH)D concentrations lower than 32 ng/mL, with significant differences between them (P<0.001). Fifteen patients (50%) had vitamin D levels <20 ng/mL and 14 had vitamin D levels between 20 and 32 ng/mL. However, these values were not associated with greater disease activity, higher levels of parathormone, medication intake, or bone mineral density. Vitamin D concentrations were similar with regard to ethnic group, body mass index, height for age, and pubertal stage. Significantly more frequently than in controls, we observed insufficient serum concentrations of 25(OH)D in patients with JSLE; however, we did not observe any association with disease activity, higher levels of parathormone, lower levels of alkaline phosphatase, use of medications, or bone mineral density alterations.

  18. Are the current Australian sun exposure guidelines effective in maintaining adequate levels of 25-hydroxyvitamin D?

    PubMed

    Kimlin, Michael; Sun, Jiandong; Sinclair, Craig; Heward, Sue; Hill, Jane; Dunstone, Kimberley; Brodie, Alison

    2016-01-01

    An adequate vitamin D status, as measured by serum 25-hydroxyvitamin D (25(OH)D) concentration, is important in humans for maintenance of healthy bones and muscle function. Serum 25(OH)D concentration was assessed in participants from Melbourne, Australia (37.81S, 144.96E), who were provided with the current Australian guidelines on sun exposure for 25(OH)D adequacy (25(OH)D ≥50 nmol/L). Participants were interviewed in February (summer, n=104) and August (winter, n=99) of 2013. Serum 25(OH)D concentration was examined as a function of measures of sun exposure and sun protection habits with control of key characteristics such as dietary intake of vitamin D, body mass index (BMI) and skin colour, that may modify this relationship. The mean 25(OH)D concentration in participants who complied with the current sun exposure guidelines was 67.3 nmol/L in summer and 41.9 nmol/L in winter. At the end of the study, 69.3% of participants who complied with the summer sun exposure guidelines were 25(OH)D adequate, while only 27.6% of participants who complied with the winter sun exposure guidelines were 25(OH)D adequate at the end of the study. The results suggest that the current Australian guidelines for sun exposure for 25(OH)D adequacy are effective for most in summer and ineffective for most in winter. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

  19. 25-Hydroxyvitamin D Concentration, Vitamin D Intake and Joint Symptoms in Postmenopausal Women

    PubMed Central

    Chlebowski, Rowan T.; Johnson, Karen C.; Lane, Dorothy; Pettinger, Mary; Kooperberg, Charles L.; Wactawski-Wende, Jean; Rohan, Tom; Jo O'Sullivan, Mary; Yasmeen, Shagufta; Hiatt, Robert A.; Shikany, James M.; Vitolins, Mara; Khandekar, Janu; Hubbell, F. Allan

    2010-01-01

    Introduction Low 25 hydroxyvitamin D (25(OH) D) concentrations have been associated with radiologic worsening of osteoarthritis in some reports. However, the results are mixed and few studies have evaluated associations between 25(OH) D concentrations and both total vitamin D intake and clinical joint symptoms. Study Design Cross-sectional analyses of information from a subset of 1993 postmenopausal women obtained at baseline entry in the Women's Health Initiative Calcium plus Vitamin D clinical trial. Main Outcome Measures 25(OH) D concentration, total vitamin D intake (diet plus supplements), presence and severity of joint pain and joint swelling. Results The 25(OH) D levels were commonly low with 53% having deficient (< 50 nmol/L) and only 17% having sufficient (> 72 nmol/L) levels. Joint pain (reported by 74%) and joint swelling (reported by 34%) were also commonly reported. 25(OH) D concentrations were modestly correlated with total vitamin D intake (R =0.29, P<0.0001); however, considerable variability in 25(OH) D concentrations for a given vitamin D intake was seen. In adjusted linear regression models, lower serum 25(OH) D concentrations were associated with higher average joint pain score (P=0.01 for trend) with differences most apparent in the lowest 25(OH) D levels sextile. Conclusions Relatively low 25(OH) D levels and a high frequency of joint symptoms were common in this population of postmenopausal women. Total vitamin D intake was only modestly associated with 25(OH) D. Low serum 25(OH) D concentrations were associated with higher joint pain scores. These findings can inform the design of future intervention trials. PMID:21093181

  20. Free 25-Hydroxyvitamin D: Impact of Vitamin D Binding Protein Assays on Racial-Genotypic Associations

    PubMed Central

    Nielson, Carrie M.; Jones, Kerry S.; Chun, Rene F.; Jacobs, Jon M.; Wang, Ying; Hewison, Martin; Adams, John S.; Swanson, Christine M.; Lee, Christine G.; Vanderschueren, Dirk; Pauwels, Steven; Prentice, Ann; Smith, Richard D.; Shi, Tujin; Gao, Yuqian; Schepmoes, Athena A.; Zmuda, Joseph M.; Lapidus, Jodi; Cauley, Jane A.; Schoenmakers, Inez; Orwoll, Eric S.

    2016-01-01

    Context: Total 25-hydroxyvitamin D (25OHD) is a marker of vitamin D status and is lower in African Americans than in whites. Whether this difference holds for free 25OHOD (f25OHD) is unclear, considering reported genetic-racial differences in vitamin D binding protein (DBP) used to calculate f25OHD. Objectives: Our objective was to assess racial-geographic differences in f25OHD and to understand inconsistencies in racial associations with DBP and calculated f25OHD. Design: This study used a cross-sectional design. Setting: The general community in the United States, United Kingdom, and The Gambia were included in this study. Participants: Men in Osteoporotic Fractures in Men and Medical Research Council studies (N = 1057) were included. Exposures: Total 25OHD concentration, race, and DBP (GC) genotype exposures were included. Outcome Measures: Directly measured f25OHD, DBP assessed by proteomics, monoclonal and polyclonal immunoassays, and calculated f25OHD were the outcome measures. Results: Total 25OHD correlated strongly with directly measured f25OHD (Spearman r = 0.84). Measured by monoclonal assay, mean DBP in African-ancestry subjects was approximately 50% lower than in whites, whereas DBP measured by polyclonal DBP antibodies or proteomic methods was not lower in African-ancestry. Calculated f25OHD (using polyclonal DBP assays) correlated strongly with directly measured f25OHD (r = 0.80–0.83). Free 25OHD, measured or calculated from polyclonal DBP assays, reflected total 25OHD concentration irrespective of race and was lower in African Americans than in US whites. Conclusions: Previously reported racial differences in DBP concentration are likely from monoclonal assay bias, as there was no racial difference in DBP concentration by other methods. This confirms the poor vitamin D status of many African-Americans and the utility of total 25OHD in assessing vitamin D in the general population. PMID:27007693

  1. 25-hydroxyvitamin D levels, race, and the progression of kidney disease.

    PubMed

    Melamed, Michal L; Astor, Brad; Michos, Erin D; Hostetter, Thomas H; Powe, Neil R; Muntner, Paul

    2009-12-01

    Black individuals have lower 25-hydroxyvitamin D [25(OH)D] levels and experience a disproportionate burden of ESRD compared with white individuals. Animal studies suggest that vitamin D has renoprotective effects. We evaluated the contribution of low 25(OH)D levels on incidence of ESRD using data from the Third National Health and Nutrition Examination Survey-linked Medicare claims files (n = 13,328). We included baseline (1988 through 1994) measurements of 25(OH)D and assessed the incidence of ESRD through July 31, 2001. Overall, 34% of non-Hispanic black individuals had 25(OH)D levels <15 ng/ml compared with 5% of non-Hispanic white individuals (P < 0.001). During a median of 9.1 yr, 65 participants developed ESRD. After adjustment for demographic, socioeconomic, and clinical and laboratory factors (including diabetes, hypertension, estimated GFR, and albuminuria), participants with 25(OH)D levels <15 ng/ml had a 2.6-fold greater incidence of ESRD than those with levels > or =15 ng/ml (incidence rate ratio 2.64; 95% confidence interval [CI] 1.00 to 7.05; P = 0.05). After adjustment for clinical covariates but not 25(OH)D levels, non-Hispanic black individuals had a 2.83-fold (95% CI 1.03 to 7.77) higher risk for developing ESRD compared with non-Hispanic white individuals. Additional adjustment for 25(OH)D levels reduced the risk by 58% (incidence rate ratio 1.77; 95% CI 0.38 to 8.21). In summary, low 25(OH)D levels associate with development of ESRD even after adjustment for multiple risk factors. Low 25(OH)D levels may account for a substantial proportion of the increased risk for ESRD experienced by black individuals.

  2. Gender dependent association of 25-hydroxyvitamin D and circulating leptin in saudi subjects: influence of dyslipidemia

    PubMed Central

    Al-Daghri, Nasser M; Rahman, Shakilur; Amer, Osama E; Al-Attas, Omar S; McTernan, Philip G; Alokail, Majed S

    2015-01-01

    Background and Objective: Leptin and vitamin D play an important role in obesity development and metabolic effects; however, the association between leptin and vitamin D is not well studied in Saudi subjects. We aimed to examine gender dependent association between serum leptin and 25-OH-VitD in adult Saudi subjects. Subjects and Methods: For this cross-sectional study in a cohort of 259 Saudi adults (100 male, age: 46.4 ± 0.9 yr [mean ± SD]; BMI: 27.8 ± 0.5 Kg/m2) and (159 female, age 46.5 ± 0.7 [mean ± SD]; BMI: 28.4 ± 0.4 Kg/m2) anthropometrics, fasting bloods, and biochemical data were collected. Serum leptin and 25-hydroxyvitamin D (vitamin D or 25-OH-VitD) were quantified using an enzyme-linked immunosorbent assay. Results: Circulating leptin and vitamin D levels were significantly higher in females compared to male (P<0.001 and P<0.01 respectively). Visceral adiposity index (VAI), triglycerides and total cholesterol were significantly higher (P<0.05, P<0.001, and P<0.05, respectively) while HDL-cholesterol were lower (P<0.001) in male compared to female subjects. In males, vitamin D levels were positively associated with leptin (r = 0.196, P<0.05). Conclusion: Vitamin D was positively associated with serum leptin in male Saudi subjects. Additionally, male subjects were found to be dyslipidemic, which might be a responsible factor for this discordant association between vitamin D and leptin in Saudi population. PMID:26379918

  3. Plasma 25-Hydroxyvitamin D During Pregnancy & Small-for-Gestational Age in Black and White Infants

    PubMed Central

    Burris, Heather H; Rifas-Shiman, Sheryl L.; Camargo, Carlos A.; Litonjua, Augusto A.; Huh, Susanna Y.; Rich-Edwards, Janet W.; Gillman, Matthew W.

    2012-01-01

    Purpose In a prospective prenatal cohort study, we examined associations of second trimester and cord plasma 25-hydroxyvitamin D (25[OH]D) with small-for-gestational age (SGA), and the extent to which vitamin D might explain black/white differences in SGA. Methods We studied 1067 white and 236 black mother-infant pairs recruited from 8 obstetrical offices early in pregnancy in Massachusetts. We analyzed 25(OH)D levels using an immunoassay and performed multivariable logistic models to estimate the odds of SGA by category of 25(OH)D level. Results Mean (standard deviation [SD]) second trimester 25(OH)D level was 60 nmol/L (21) and was lower for black (46 nmol/L [22]) than white (62 nmol/L [20]) women. 59 infants were SGA (4.5%) and more black than white infants were SGA (8.5% vs. 3.7%). The odds of SGA were higher with maternal 25(OH)D levels <25 vs. ≥25 nmol/L (adjusted odds ratio [OR] 3.17; 95% confidence interval [CI]:1.16, 8.63). The increased odds of SGA among black vs. white participants decreased from an OR of 2.04(1.04, 4.04) to 1.68(0.82, 3.46) after adjusting for 25(OH)D. Conclusions Second trimester 25(OH)D levels <25 nmol/L were associated with higher odds of SGA. Our data raise the possibility that Vitamin D status may contribute to racial disparities in SGA. PMID:22658824

  4. Higher milk fat content is associated with higher 25-hydroxyvitamin D concentration in early childhood.

    PubMed

    Vanderhout, Shelley M; Birken, Catherine S; Parkin, Patricia C; Lebovic, Gerald; Chen, Yang; O'Connor, Deborah L; Maguire, Jonathon L

    2016-05-01

    Current guidelines for cow's milk consumption in children older than age 2 years suggest 1% or 2% milk to reduce the risk of obesity. Given that milk is the main dietary source of vitamin D for North American children and that vitamin D is fat soluble, we hypothesized 25-hydroxyvitamin D (25(OH)D) concentration to be positively associated with the fat content of milk. The objective was to determine the relationship between the fat content of milk consumed and the serum 25(OH)D concentration; our secondary objective was to explore the role that the volume of milk consumed played in this relationship. We completed a cross-sectional study of children aged 12-72 months in the TARGetKids! research network. Multivariable linear regression was used to test the association between milk fat content and child 25(OH)D, adjusted for clinically relevant covariates. The interaction between volume of milk and fat content was examined. Two thousand eight hundred fifty-seven children were included in the analysis. The fat content of milk was positively associated with 25(OH)D (p = 0.03), and the interaction between the volume of milk consumed and the milk fat content was statistically significant (p = 0.005). Children who drank 1% milk needed 2.46 cups (95% confidence interval (CI) 2.38-2.54) of milk to have a 25(OH)D concentration similar to that of children who drank 1 cup of homogenized milk (3.25% fat). Children who consumed 1% milk had 2.05 (95% CI 1.73-2.42) times higher odds of having a 25(OH)D concentration <50 nmol/L compared with children who consumed homogenized milk. In conclusion, recommendations for children to drink lower-fat milk (1% or 2%) may compromise serum 25(OH)D levels and may require study to ensure optimal childhood health.

  5. The Prevalence of 25-hydroxyvitamin D Deficiency in Japanese Patients with Diabetic Nephropathy.

    PubMed

    Kondo, Masumi; Toyoda, Masao; Miyatake, Han; Tanaka, Eitaro; Koizumi, Masahiro; Komaba, Hirotaka; Kimura, Moritsugu; Umezono, Tomoya; Fukagawa, Masafumi

    2016-01-01

    Objective The purpose of this study was to measure serum 25-hydroxyvitamin D [25(OH)D] levels in Japanese patients with diabetic nephropathy and determine the relationship between 25(OH)D concentrations and various factors. Methods The study subjects included 442 patients with type 2 diabetes. Their serum levels of creatinine, HbA1c, intact-parathyroid hormone, urinary albumin, 25(OH)D, and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured and their estimated glomerular filtration rate (eGFR) was determined. The patients were divided into four groups based on the risk for progression to chronic kidney disease (CKD): low, moderate, high, very high, based on their eGFR and their level of albuminuria. Results The median 25(OH)D level was 14.6 ng/mL; 11% of the patients had 25(OH)D deficiency (<10 ng/mL), and 2% of patients had active vitamin D deficiency, as defined by a 1,25(OH)2D level of <22 pg/mL. The serum 25(OH)D level was correlated with the serum 1,25(OH)2D level in patients with a very high risk for CKD, but not in those with a moderate or high risk for CKD. Conclusion Although the vitamin D levels of the Japanese patients with diabetic nephropathy and CKD were low, the prevalence of vitamin D deficiency, as defined by the 1,25(OH)2D level, was low. Albuminuria, younger age, and female gender were associated with a low 25(OH)D level. The serum level of 25(OH)D should be monitored to assess the vitamin D status of patients with nephropathy and CKD. PMID:27629947

  6. Plasma 25-hydroxyvitamin D concentrations and periodontal disease in postmenopausal women

    PubMed Central

    Millen, Amy E.; Hovey, Kathleen M.; LaMonte, Michael J.; Swanson, Mya; Andrews, Christopher A.; Kluczynski, Melissa A.; Genco, Robert J.; Wactawski-Wende, Jean

    2013-01-01

    Background Vitamin D has anti-inflammatory and anti-microbial properties that, together with its influence on bone health, may confer periodontal benefit. Methods We investigated cross-sectional associations (1997–2000) between plasma 25-hydroxyvitamin D concentrations [25(OH)D] and periodontal measure among 920 postmenopausal women. Chronic measures of disease were defined based on: 1) alveolar crestal height (ACH) measures from intraoral radiographs and tooth loss, and the 2) Center for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) criteria using measures of clinical attachment level (CAL) and probing pocket depth (PD). Acute oral inflammation was assessed by the % of gingival sites that bled upon assessment with a probe. Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) for periodontal disease among participants with adequate ([25(OH)D]≥50 nmol/L) compared to deficient/inadequate ([25(OH)D]<50 nmol/L) vitamin D status adjusted for age, dental visit frequency, and body mass index. Results No association was observed between vitamin D status and periodontal disease defined by ACH and tooth loss (adjusted OR=0.96, 95% CI: 0.68–1.35). In contrast, women with adequate compared to deficient/inadequate vitamin D status had a 33% lower odds (95% CI: 5%–53%) of periodontal disease defined using the CDC/AAP definition and a 42% lower odds (95% CI: 21%-58%) of having ≥50% of gingival sites that bled. Conclusion Vitamin D status was inversely associated with gingival bleeding, an acute measure of oral health and inflammation and inversely associated with clinical categories of chronic periodontal disease that incorporated PD, an indicator of oral inflammation. However, vitamin D was not associated with chronic periodontal disease based on measures of ACH in combination with tooth loss. PMID:23259413

  7. Association of plasma 25-hydroxyvitamin D concentrations and pathogenic oral bacteria in postmenopausal women

    PubMed Central

    Sahli, Michelle W; Wactawski-Wende, Jean; Ram, Pavani K; LaMonte, Michael J.; Hovey, Kathleen M.; Genco, Robert J.; Andrews, Christopher A.; Millen, Amy E.

    2014-01-01

    Background Previous findings of an association between 25-hydroxyvitamin D (25(OH)D) concentrations and periodontal disease, may be partially explained by vitamin D’s antimicrobial properties. To our knowledge, no study has investigated the association between 25(OH)D and pathogenic oral bacteria, a putative cause of periodontal disease. Methods We examined the association between plasma 25(OH)D concentrations and pathogenic oral bacteria among postmenopausal women in the Buffalo Osteoporosis and Periodontal Disease Study (1997–2000), an ancillary study of the Women’s Health Initiative Observational Study. Subgingival plaque samples were assessed using immunofluorescence for the presence of Porphyromonas gingivalis, Tannerella forsythensis, Fusobacterium nucleatum, Prevotella intermedia and Campylobacter rectus. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for prevalent bacteria by quintile (Q) of 25(OH)D concentrations adjusting for age and body mass index. Results Of the 855 participants, 288 (34%) had deficient/inadequate (<50 nmol/L) 25(OH)D concentrations and 497 (58%) had at least one species of pathogenic bacteria. No significant association was found between 25(OH)D and presence of any of these bacteria (adjusted OR for high (Q5) compared to low (Q1) 25(OH)D=0.96; 95% CI: 0.61–1.50, p for trend=0.50). Inverse, although not statistically significant, associations were found between 25(OH)D and more than one species of pathogenic bacteria (adjusted OR for adequate compared to deficient/inadequate 25(OH)D=0.85; 95% CI: 0.60–1.19). Conclusions No association was observed between pathogenic oral bacteria and 25(OH)D concentrations in postmenopausal women. This may be due to the species of bacteria assessed, small effect size or a true absence of an association. PMID:24261910

  8. Association between Plasma 25-Hydroxyvitamin D, Ancestry and Aggressive Prostate Cancer among African Americans and European Americans in PCaP

    PubMed Central

    Steck, Susan E.; Arab, Lenore; Zhang, Hongmei; Bensen, Jeannette T.; Fontham, Elizabeth T. H.; Johnson, Candace S.; Mohler, James L.; Smith, Gary J.; Su, Joseph L.; Trump, Donald L.; Woloszynska-Read, Anna

    2015-01-01

    Background African Americans (AAs) have lower circulating 25-hydroxyvitamin D3 [25(OH)D3] concentrations and higher prostate cancer (CaP) aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OH)D3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs). Methods Plasma 25(OH)D3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) classified as having either ‘high’ or ‘low’ aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OH)D3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR) and 95% confidence intervals (95%CI) for high aggressive CaP by tertile of plasma 25(OH)D3. Results AAs with highest percent African ancestry (>95%) had the lowest mean plasma 25(OH)D3 concentrations. Overall, plasma 25(OH)D3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (ORT3vs.T1: 2.23, 95%CI: 1.26–3.95 among men with low calcium intake, and ORT3vs.T1: 0.19, 95%CI: 0.05–0.70 among men with high calcium intake). Among EAs, the point estimates of the ORs were <1.0 for the upper tertiles with CIs that included the null. Conclusions Among AAs, plasma 25(OH)D3 was associated positively with CaP aggressiveness among men with low calcium intake and inversely among men with high calcium intake. The clinical significance of circulating concentrations of 25(OH)D3 and interactions with calcium intake in the AA population warrants further study. PMID:25919866

  9. Measurement of 25-hydroxyvitamin D2&3 and 1, 25-dihydroxyvitamin D2&3 by Tandem Mass Spectrometry: A Primate Multispecies Comparison

    PubMed Central

    Ziegler, Toni E.; Kapoor, Amita; Hedman, Curtis J.; Binkley, Neil; Kemnitz, Joseph W.

    2015-01-01

    Vitamin D metabolites are widely studied for their roles in bone health, immune functions and other potential physiologic roles in humans. However, the optimal blood levels of vitamin D metabolites are still unclear. Various methods for measuring vitamin D metabolites have been used and recently liquid chromatography tandem mass spectroscopy (LC-MS/MS) has been adopted as the gold standard for vitamin D metabolite measurement. Here we report the use of LC-MS/MS to measure 25-hydroxyvitamin D (25(OH)D2&3), and 1,25-dihydroxyvitamin D (1,25(OH)2D2&3), in three laboratory nonhuman primate species: common marmoset (Callithrix jacchus), rhesus macaque (Macaca mulatta), and cynomolgus macaque (Macaca fascicularis), and compare them to humans using the same technique. The nonhuman primates showed blood levels for 25(OH)D3 and 1,25(OH)2D3 significantly higher than human values with marmosets having the highest levels. Marmoset samples showed significantly more variability among individuals than those from macaques for both metabolites, but all three nonhuman primate species exhibited large variation within species for both 25(OH)D2&3 and 1,25(OH)2D2&3. Marmoset females had significantly lower values than the males for 25(OH)D3, while rhesus males showed a significant decrease in 25(OH)D3 with age. The most striking finding is the variation within species for vitamin D levels even in laboratory primates that have a controlled diet, UV exposure, and in some cases, genetic constraints. Similar variation in 25(OH)D responses to a fixed dose of oral vitamin D supplementation has been reported in humans. We suggest that these species can provide primate models for examining the factors influencing variation in the levels of vitamin D necessary for human and nonhuman primate health. PMID:25845705

  10. 1,25-Dihydroxyvitamin D3 Enhances Innate Immune Responses of Bovine Mammary Epithelial Cells that are Triggered by Toll-like Receptor Signaling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) has been found to play an important role in the bovine innate immune response. 1,25(OH)2D3 is the active vitamin D metabolite and is produced from the major circulating metabolite, 25-hydroxyvitamin D3, by the enzyme 1alpha-hydroxylase (1alpha-OHase)...

  11. New, tritium-release assay for 25-hydroxyvitamin D-1. cap alpha. -hydroxylase

    SciTech Connect

    Brown, A.J.; Perlman, K.; DeLuca, H.F.

    1986-05-01

    A new, rapid assay for 25-hydroxyvitamin D (25-OH-D)-1..cap alpha..-hydroxylase has been developed using 25-OH-(1..cap alpha..-/sup 3/H)D/sub 3/ as substrate. This compound was prepared by reduction of 1-oxo-25-hydroxycyclovitamin D/sub 3/ with (/sup 3/H)NaBH/sub 4/, separation of the 1..cap alpha..- and 1..beta..-hydroxy products by HPLC, subsequent treatments with methylsulfonylchloride and lithium aluminum hydride, cycloreversion, and saponification. The 1..cap alpha..- and 1..beta..-tritiated substrates were tested in the solubilized and reconstituted chick 1..cap alpha..-hydroxylase system. After incubation, the reaction mixture was passed through a reversed phase silica cartridge to separate (/sup 3/H)H/sub 2/O from the labeled substrate. The cartridges were then washed with methanol to elute all vitamin D metabolites, and the amount of 1,25-(OH)/sub 2/(/sup 3/H)D/sub 3/ was measured by HPLC. In addition, identical reaction mixtures using 25-OH-(26,27-/sup 3/H)D/sub 3/ as substrate were extracted and analyzed by HPLC for 1,25-(OH)/sub 2/(/sup 3/H)D/sub 3/. Reactions with 25-OH-(1..cap alpha..-/sup 3/H)D/sub 3/ produced (/sup 3/H)H/sub 2/O comparable to the amount of 1,25-(OH)/sub 2/(26,27-/sup 3/H)D/sub 3/ and negligible (/sup 3/H) in 1,25-(OH)/sub 2/D/sub 3/. Conversely, reactions with 25-OH-(1..beta..-/sup 3/H)D/sub 3/ produced negligible (/sup 3/H)H/sub 2/O but produced 1,25-(OH)/sub 2/(/sup 3/H)D/sub 3/ comparable to that from reactions with 25-OH-(26,27-/sup 3/H)D/sub 3/. The results indicate that 1..cap alpha..-hydroxylation specifically displaces the 1..cap alpha..-hydrogen of 25-OH-D/sub 3/ and that the release of the 1..cap alpha..-/sup 3/H provides an accurate measure of vitamin D 1..cap alpha..-hydroxylation.

  12. Temporal trends and determinants of longitudinal change in 25-hydroxyvitamin D and parathyroid hormone levels.

    PubMed

    Berger, Claudie; Greene-Finestone, Linda S; Langsetmo, Lisa; Kreiger, Nancy; Joseph, Lawrence; Kovacs, Christopher S; Richards, J Brent; Hidiroglou, Nick; Sarafin, Kurtis; Davison, K Shawn; Adachi, Jonathan D; Brown, Jacques; Hanley, David A; Prior, Jerilynn C; Goltzman, David

    2012-06-01

    Vitamin D is essential for facilitating calcium absorption and preventing increases in parathyroid hormone (PTH), which can augment bone resorption. Our objectives were to examine serum levels of 25-hydroxyvitamin D [25(OH)D] and PTH, and factors related to longitudinal change in a population-based cohort. This is the first longitudinal population-based study looking at PTH and 25(OH)D levels. We analyzed 3896 blood samples from 1896 women and 829 men in the Canadian Multicentre Osteoporosis Study over a 10-year period starting in 1995 to 1997. We fit hierarchical models with all available data and adjusted for season. Over 10 years, vitamin D supplement intake increased by 317 (95% confidence interval [CI] 277 to 359) IU/day in women and by 193 (135 to 252) IU/day in men. Serum 25(OH)D (without adjustment) increased by 9.3 (7.3 to 11.4) nmol/L in women and by 3.5 (0.6 to 6.4) nmol/L in men but increased by 4.7 (2.4 to 7.0) nmol/L in women and by 2.7 (-0.6 to 6.2) nmol/L in men after adjustment for vitamin D supplements. The percentage of participants with 25(OH)D levels <50 nmol/L was 29.7% (26.2 to 33.2) at baseline and 19.8% (18.0 to 21.6) at year 10 follow-up. PTH decreased over 10 years by 7.9 (5.4 to 11.3) pg/mL in women and by 4.6 (0.2 to 9.0) pg/mL in men. Higher 25(OH)D levels were associated with summer, younger age, lower body mass index (BMI), regular physical activity, sun exposure, and higher total calcium intake. Lower PTH levels were associated with younger age and higher 25(OH)D levels in both women and men and with lower BMI and participation in regular physical activity in women only. We have observed concurrent increasing 25(OH)D levels and decreasing PTH levels over 10 years. Secular increases in supplemental vitamin D intake influenced both changes in serum 25(OH)D and PTH levels.

  13. Low Serum 25-Hydroxyvitamin D Levels Are Associated with Dry Eye Syndrome

    PubMed Central

    Yoon, Sam Young; Bae, Seok Hyun; Shin, Young Joo; Park, Shin Goo; Hwang, Sang-Hee; Hyon, Joon Young; Wee, Won Ryang

    2016-01-01

    Background Dry eye syndrome (DES) is a common tear film and ocular surface disease that results in discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. Systemic diseases associated with DES include diabetes mellitus, rheumatoid arthritis, depression, anxiety, thyroid disease, allergic diseases, irritable bowel syndrome, chronic pain syndrome, and hyperlipidemia. Interestingly, it has been found that most of these are associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) or inadequate sunlight exposure. Methods In this cross-sectional data analysis, noninstitutionalized adults aged ≥19 years (N = 17,542) who participated in Korean National Health and Nutrition Examination Survey 2010–2012 were included. Information regarding duration of sunlight exposure was collected from the survey participants. Serum 25(OH)D and zinc levels were measured. The confounding variables were age, gender, sunlight exposure time, region of residence, obesity, serum 25(OH)D level, diabetes mellitus, rheumatoid arthritis, depression, thyroid disorder, atopic dermatitis, history of ocular surgery, regular exercise, and walking exercise. Results Mean serum 25(OH)D levels of subjects with and without DES were 16.90 ± 6.0 and 17.52 ± 6.07 (p<0.001). Inadequate sunlight exposure time (odds ratio [OR], 1.554; 95% confidence interval [CI], 1.307–1.848), urban residence (OR, 1.669; 95% CI, 1.456–1.913), indoor occupation (OR, 1.578; 95% CI, 1.389–1.814), and low serum 25(OH)D level (OR, 1.158; 95% CI, 1.026–1.308) were the risk factors for DES. After adjusting for age, sex, obesity, diabetes mellitus, rheumatoid arthritis, depression, thyroid disorder, atopic dermatitis, history of ocular surgery, regular exercise, and occupation, low serum 25(OH)D level (OR, 1.178; 95% CI, 1.010–1.372) and deficient sunlight exposure time (OR, 1.383; 95% CI, 1.094–1.749) were the risk factors for diagnosed DES. Conclusion Low serum 25

  14. Temporal trends and determinants of longitudinal change in 25-hydroxyvitamin D and parathyroid hormone levels.

    PubMed

    Berger, Claudie; Greene-Finestone, Linda S; Langsetmo, Lisa; Kreiger, Nancy; Joseph, Lawrence; Kovacs, Christopher S; Richards, J Brent; Hidiroglou, Nick; Sarafin, Kurtis; Davison, K Shawn; Adachi, Jonathan D; Brown, Jacques; Hanley, David A; Prior, Jerilynn C; Goltzman, David

    2012-06-01

    Vitamin D is essential for facilitating calcium absorption and preventing increases in parathyroid hormone (PTH), which can augment bone resorption. Our objectives were to examine serum levels of 25-hydroxyvitamin D [25(OH)D] and PTH, and factors related to longitudinal change in a population-based cohort. This is the first longitudinal population-based study looking at PTH and 25(OH)D levels. We analyzed 3896 blood samples from 1896 women and 829 men in the Canadian Multicentre Osteoporosis Study over a 10-year period starting in 1995 to 1997. We fit hierarchical models with all available data and adjusted for season. Over 10 years, vitamin D supplement intake increased by 317 (95% confidence interval [CI] 277 to 359) IU/day in women and by 193 (135 to 252) IU/day in men. Serum 25(OH)D (without adjustment) increased by 9.3 (7.3 to 11.4) nmol/L in women and by 3.5 (0.6 to 6.4) nmol/L in men but increased by 4.7 (2.4 to 7.0) nmol/L in women and by 2.7 (-0.6 to 6.2) nmol/L in men after adjustment for vitamin D supplements. The percentage of participants with 25(OH)D levels <50 nmol/L was 29.7% (26.2 to 33.2) at baseline and 19.8% (18.0 to 21.6) at year 10 follow-up. PTH decreased over 10 years by 7.9 (5.4 to 11.3) pg/mL in women and by 4.6 (0.2 to 9.0) pg/mL in men. Higher 25(OH)D levels were associated with summer, younger age, lower body mass index (BMI), regular physical activity, sun exposure, and higher total calcium intake. Lower PTH levels were associated with younger age and higher 25(OH)D levels in both women and men and with lower BMI and participation in regular physical activity in women only. We have observed concurrent increasing 25(OH)D levels and decreasing PTH levels over 10 years. Secular increases in supplemental vitamin D intake influenced both changes in serum 25(OH)D and PTH levels. PMID:22407786

  15. Plasma 25-hydroxyvitamin D and risk of premenstrual syndrome in a prospective cohort study

    PubMed Central

    2014-01-01

    Background Moderate to severe premenstrual syndrome (PMS) affects 8–20 percent of premenopausal women. Previous studies suggest that high dietary vitamin D intake may reduce risk. However, vitamin D status is influenced by both dietary vitamin D intake and sunlight exposure and the association of vitamin D status with PMS remains unclear. Methods We assessed the relation of plasma 25-hydroxyvitamin D (25OHD), total calcium and parathyroid hormone levels with risk of PMS and specific menstrual symptoms in a case–control study nested within the prospective Nurses’ Health Study II. Cases were 401 women free from PMS at baseline who developed PMS during follow-up (1991–2005). Controls were women not experiencing PMS (1991–2005), matched 1:1 with cases on age and other factors. Timed luteal phase blood samples were collected between 1996 and 1999 from cases and controls. We used conditional logistic regression to model the relation of 25OHD levels with risk of PMS and individual menstrual symptoms. Results In analyses of all cases and controls, 25OHD levels were not associated with risk of PMS. However, results differed when the timing of blood collection vs. PMS diagnosis was considered. Among cases who had already been diagnosed with PMS at the time of blood collection (n = 279), 25OHD levels were positively associated with PMS, with each 10 nmol/L change in 25OHD associated with a 13% higher risk. Among cases who developed PMS after blood collection (n = 123), 25OHD levels were unrelated to risk of PMS overall, but inversely related to risk of specific menstrual symptoms. For example, each 10 nmol/L increase was associated with a significant 21% lower risk of breast tenderness (P = 0.02). Total calcium or parathyroid hormone levels were unrelated to PMS. Conclusions 25OHD levels were not associated with overall risk of PMS. The positive association observed among women already experiencing PMS at the time of 25OHD measurement is likely due to

  16. Serum 25 Hydroxyvitamin D, Bone Mineral Density and Fracture Risk Across the Menopause

    PubMed Central

    Greendale, Gail A.; Ruppert, Kristine; Lian, Yinjuan; Randolph, John F.; Lo, Joan C.; Burnett-Bowie, Sherri-Ann; Finkelstein, Joel S.

    2015-01-01

    Context: Low levels of serum 25 Hydroxyvitamin D [25(OH)D] have been linked to greater fracture risk in older women. Objective: This study aimed to determine whether higher 25(OH)D is associated with slower loss of bone mineral density (BMD) and lower fracture risk during the menopausal transition. Design, Setting, and Participants: This was a prospective cohort study at five clinical centers in the United States. Mean age was 48.5 ± 2.7 years. The fracture analysis included 124 women with an incident traumatic fracture, 88 with incident nontraumatic fracture, and 1532 women without incident fractures; average followup was 9.5 years. BMD analysis included 922 women with a documented final menstrual period. Main Outcome Measures: Serum 25(OH)D was measured by liquid chromatography tandem mass spectrometry at the third annual clinic visit. BMD was measured and incident fractures ascertained at each annual visit. Results: The mean 25(OH)D was 21.8 ng/mL; seven-hundred two (43%) of the women had 25(OH)D values <20 ng/mL. There was no significant association between 25(OH)D and traumatic fractures. In multivariate adjusted hazards models, the hazard ratio (HR) for nontraumatic fractures (95% confidence interval [CI]) was 0.72 (0.54–0.96) for each 10-ng/mL increase in 25(OH)D. Comparing women whose 25(OH)D was ≥20 vs <20 ng/mL, the HR (95% CI) for fracture was 0.54 (0.32–0.89). Changes in lumbar spine and femoral neck bone mineral density across menopause were not significantly associated with serum 25(OH)D level. Conclusion: Serum 25(OH)D levels are inversely associated with nontraumatic fracture in mid-life women. Vitamin D supplementation is warranted in midlife women with 25(OH)D levels <20 ng/mL. PMID:25719933

  17. Serum 25-Hydroxyvitamin D Levels: Variability, Knowledge Gaps, and the Concept of a Desirable Range.

    PubMed

    Fuleihan, Ghada El-Hajj; Bouillon, Roger; Clarke, Bart; Chakhtoura, Marlene; Cooper, Cyrus; McClung, Michael; Singh, Ravinder J

    2015-07-01

    Hypovitaminosis D is prevalent worldwide but proportions vary widely between regions, depending on genetic and lifestyle factors, the threshold to define deficiency, and accuracy of 25-hydroxyvitamin D (25OHD) assays used. Latitude, pollution, concealing clothing, sun exposure, gender, dietary habits, and lack of government regulation account for up to 50% in variations in serum 25OHD levels, whereas genetic polymorphisms in the vitamin D pathway account for less than 5%. Organizations/societies have developed guidelines for recommended desirable 25OHD levels and vitamin D doses to reach them, but their applicability across age groups and populations are still debated. This article and the accompanying online Supporting Information highlight sources of variations in circulating 25OHD levels, uncertainties and knowledge gaps, and analytical problems facing 25OHD assays, while keeping efficacy and safety data as the dominant factors when defining a desirable range for 25OHD levels. We propose a desirable range of 20 to 40 ng/mL (50 to 100 nmol/L), provided precise and accurate assays are used. Although slightly lower levels, 15 to 20 ng/mL, may be sufficient for some infants and adults, higher levels, 40 to 60 ng/mL, may still be safe. This desirable range allows physicians to tailor treatment while taking season, lifestyle, vitamin D intake, and other sources of variation into account. We reserve 25OHD measurements for at-risk patients, defined by disease or lifestyle, and the use of 25OHD assays calibrated against the recommended international standards. Most target groups reach desirable target levels by a daily intake of 400 to 600 IU for children and 800 IU for adults. A total daily allowance of vitamin D of up to 1000 IU in the pediatric age groups, and up to 2000 IU in adults, tailored to an individual patient risk profile, is probably safe over long durations. Additional data are needed to validate the proposed range and vitamin D doses

  18. Predictors of 25-hydroxyvitamin D Levels in HIV-infected Patients in Hawai‘i

    PubMed Central

    Chow, Dominic C; Liang, Chin-Yuan; Nakamoto, Beau K; Umaki, Tracie M; Kallianpur, Kalpana J; Shikuma, Cecilia M

    2013-01-01

    HIV-infected individuals are at increased risk for several metabolic diseases, including low 25-hydroxyvitamin D [25(OH)D]. Data on the prevalence and risk factors for low 25(OH)D in HIV patients living in the tropics is scarce. Patients ≥ 40 years old on stable antiretroviral therapy were enrolled from March 2009 to July 2011 in Hawai‘i (latitude 21° North). Chemiluminescent immunoassay (DiaSorin) was used to determine plasma 25(OH)D levels. Patients were grouped by whether 25(OH)D was collected in summer (May 1 – September 30) or winter (October 1 – April 30). Of 158 patients enrolled, 88 (56%) and 70 (44%) were enrolled in winter and summer, respectively. There were 57.6% Caucasians and 88% men. Over-all median (quartile1, quartile3) age was 51 (46, 57) years and median 25(OH)D was 32.4 (24.0, 41.0) ng/ml. Forty-three percent (n=68) had 25(OH)D<30.0 ng/ml. Median 25(OH)D levels were 29.6 (22.0, 38.0) ng/ml in winter and 36.9 (25.0, 44.5) ng/ml in summer (P = .01). Median body mass index (BMI) of winter patients was significantly higher (P = .03). By simple linear regression, log-transformed 25(OH)D was significantly associated with winter visit (β = −.0737, P = .01), ethnicity (Caucasian versus non-Caucasian, β = .1194, P < .01), BMI (β = −.0111, P < .01) and current use of zidovudine (β = −.1233, P = .03). In multiple linear regression, only Caucasian ethnicity (β = .1004, P < .01) and BMI (β = −.0078, P = .02) retained statistical significance. Seasonal variation in 25(OH)D was observed but the significance of winter visit was not preserved in the final multivariate model. Ethnicity and BMI were better predictors of 25(OH)D levels than season in the tropics. PMID:23795329

  19. Serum 25-Hydroxyvitamin D and Cancer Mortality in the NHANES III Study (1988–2006)

    PubMed Central

    Freedman, D. Michal; Looker, Anne C.; Abnet, Christian C.; Linet, Martha S.; Graubard, Barry I.

    2010-01-01

    Vitamin D has been hypothesized to protect against cancer. We followed 16,819 participants in NHANES III from 1988 through 2006, expanding upon an earlier NHANES III study (1988–2000). Using Cox proportional hazard regression models, we examined risk related to baseline serum 25-hydroxyvitamin D (25(OH)D) for total cancer mortality, in both sexes, and by racial/ethnic groups, as well as for site-specific cancers. Because serum was collected in the south in cooler months and the north in warmer months, we examined associations by collection season (“summer/higher latitude” and “winter/lower latitude”). We identified 884 cancer deaths during 225,212 person-years. Overall cancer mortality risks were unrelated to baseline 25(OH)D status in both season/latitude groups, and in non-Hispanic whites, non-Hispanic blacks, and Mexican-Americans. In men, risks were elevated at higher levels (e.g., for ≥100 nmol/L, RR=1.85 (95% CI=1.02–3.35) compared to <37.5 nmol/L). Athough risks were unrelated to 25(OH)D in all women combined, risks significantly decreased with increasing 25(OH)D in the summer/higher latitude group (for ≥100 nmol/L, RR= 0.52 (95% CI=0.25–1.15) compared to <37.5 nmol/L, P-trend=0.03, based on continuous values). We also observed a suggestion of an inverse association with colorectal cancer mortality(P-trend=0.09) and a positive association with lung cancer mortality among males (P-trend=0.03). Our results do not support a the hypothesis that 25(OH)D is associated with reduced cancer mortality. Although cancer mortality in females was inversely associated with 25(OH)D in the summer/higher latitude group, cancer mortality at some sites was increased among men with higher 25(OH)D. These findings argue for caution before increasing 25(OH)D levels to prevent cancer. PMID:20847342

  20. Common Variation in Vitamin D Pathway Genes Predicts Circulating 25-Hydroxyvitamin D Levels among African Americans

    PubMed Central

    Signorello, Lisa B.; Shi, Jiajun; Cai, Qiuyin; Zheng, Wei; Williams, Scott M.; Long, Jirong; Cohen, Sarah S.; Li, Guoliang; Hollis, Bruce W.; Smith, Jeffrey R.; Blot, William J.

    2011-01-01

    Vitamin D is implicated in a wide range of health outcomes, and although environmental predictors of vitamin D levels are known, the genetic drivers of vitamin D status remain to be clarified. African Americans are a group at particularly high risk for vitamin D insufficiency but to date have been virtually absent from studies of genetic predictors of circulating vitamin D levels. Within the Southern Community Cohort Study, we investigated the association between 94 single nucleotide polymorphisms (SNPs) in five vitamin D pathway genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1) and serum 25-hydroxyvitamin D (25(OH)D) levels among 379 African American and 379 Caucasian participants. We found statistically significant associations with three SNPs (rs2298849 and rs2282679 in the GC gene, and rs10877012 in the CYP27B1 gene), although only for African Americans. A genotype score, representing the number of risk alleles across the three SNPs, alone accounted for 4.6% of the variation in serum vitamin D among African Americans. A genotype score of 5 (vs. 1) was also associated with a 7.1 ng/mL reduction in serum 25(OH)D levels and a six-fold risk of vitamin D insufficiency (<20 ng/mL) (odds ratio 6.0, p = 0.01) among African Americans. With African ancestry determined from a panel of 276 ancestry informative SNPs, we found that high risk genotypes did not cluster among those with higher African ancestry. This study is one of the first to investigate common genetic variation in relation to vitamin D levels in African Americans, and the first to evaluate how vitamin D-associated genotypes vary in relation to African ancestry. These results suggest that further evaluation of genetic contributors to vitamin D status among African Americans may help provide insights regarding racial health disparities or enable the identification of subgroups especially in need of vitamin D-related interventions. PMID:22205958

  1. 25-Hydroxyvitamin D and Parathyroid Hormone Levels Are Independently Associated with the Hemoglobin A1c Level of Korean Type 2 Diabetic Patients: The Dong-Gu Study

    PubMed Central

    Choi, Jin-Su; Rhee, Jung-Ae; Nam, Hae-Sung; Jeong, Seul-Ki; Park, Kyeong-Soo; Kim, Hee Nam; Shin, Min-Ho

    2016-01-01

    In type 2 diabetic patients, the relationships between 25-hydroxyvitamin D and parathyroid hormone levels, and glycemic control, remain unclear. We evaluated associations between 25-hydroxyvitamin D, parathyroid hormone, and hemoglobin A1c levels after adjusting for other covariates, including log transformed 25-hydroxyvitamin D levels and log transformed parathyroid hormone levels, in Korean patients with type 2 diabetes. In total, 1,175 patients with type 2 diabetes were selected from 8,857 individuals who completed the baseline survey of the Dong-gu study, conducted in Korea from 2007 to 2010. After adjusting for other covariates, we found that the mean hemoglobin A1c level was inversely associated with the 25-hydroxyvitamin D level (Q1: 7.47% [7.30–7.63], Q2: 7.25% [7.09–7.40], Q3: 7.17% [7.02–7.32], Q4: 7.19% [7.02–7.35]; p for trend = 0.021, p for between groups = 0.050) and the parathyroid hormone level (Q1: 7.35% [7.19–7.51], Q2: 7.34% [7.19–7.50], Q3: 7.28% [7.13–7.43], Q4: 7.09% [6.94–7.24]; p for trend = 0.022, p for between groups = 0.048). However, the mean fasting glucose level was not associated with either the 25-hydroxyvitamin D or parathyroid hormone level. In conclusion, inverse associations were evident between hemoglobin A1c, 25-hydroxyvitamin D and parathyroid hormone levels in Korean patients with type 2 diabetes. The associations remained significant after adjusting for other covariates, including the log transformed 25-hydroxyvitamin D levels and log transformed parathyroid hormone levels. PMID:27362844

  2. Lack of association between serum 25-hydroxyvitamin D levels and cervical human papillomavirus infection in systemic lupus erythematosus.

    PubMed

    García-Carrasco, M; Mendoza-Pinto, C; Munguía-Realpozo, P; Rodríguez-Gallegos, A; Vallejo-Ruiz, V; Muñoz-Guarneros, M; Méndez-Martínez, S; Soto-Santillán, P; Pezzat-Said, E; Reyes-Leyva, J; López-Colombo, A; Ruiz-Argüelles, A; Cervera, R

    2015-05-01

    Our objective was to evaluate whether vitamin D deficiency is associated with cervical human papilloma virus (HPV) infection in women with SLE. This is a cross-sectional study of 67 women with SLE. A structured questionnaire was administered to ascertain the possible risk factors associated with cervical HPV infection. A gynaecological evaluation and cervical cytology screening were made. HPV detection and genotyping was made by PCR and linear array assay. Serum 25 hydroxyvitamin D levels were quantified by chemiluminescence immunoassay. Mean age and disease duration were 44.8 ± 10.6 and 42.5 ± 11.8 years, respectively. Demographic characteristics were similar in patients with and without deficiency (<20 ng/ml and ≥20 ng/ml). There were 28.4% of women with cervical HPV infection and 68.4% had high-risk HPV infections. Patients with 25 hydroxyvitamin D levels <20 ng/ml had a higher prevalence of cervical HPV infection than those with levels ≥20 ng/ml (30.7% vs. 25.8%; p = 0.72). We found no significant difference when high-risk HPV infection was evaluated (36.8% vs. 31.5%; p = 0.73). In conclusion, women with SLE have a high prevalence of vitamin D deficiency and cervical HPV infection. However, we found no association between vitamin D deficiency and cervical HPV.

  3. Modulation of the Bovine Innate Immune Response by Production of 1alpha,25-Dihydroxyvitamin D3 in Bovine Monocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In cattle, the kidney has been the only known site for production of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) from 25-hydroxyvitamin D3 25(OH)D3 by 1alpha-hydroxylase (1alpha-OHase). However, recent studies have shown that human monocytes express 1alpha-OHase and produce 1,25(OH)2D3 in response to to...

  4. Analytical Bias in the Measurement of Serum 25-Hydroxyvitamin D Concentrations Impairs Assessment of Vitamin D Status in Clinical and Research Settings

    PubMed Central

    Black, Lucinda J.; Anderson, Denise; Clarke, Michael W.; Ponsonby, Anne-Louise; Lucas, Robyn M.

    2015-01-01

    Measured serum 25-hydroxyvitamin D concentrations vary depending on the type of assay used and the specific laboratory undertaking the analysis, impairing the accurate assessment of vitamin D status. We investigated differences in serum 25-hydroxyvitamin D concentrations measured at three laboratories (laboratories A and B using an assay based on liquid chromatography-tandem mass spectrometry and laboratory C using a DiaSorin Liaison assay), against a laboratory using an assay based on liquid chromatography-tandem mass spectrometry that is certified to the standard reference method developed by the National Institute of Standards and Technology and Ghent University (referred to as the ‘certified laboratory’). Separate aliquots from the same original serum sample for a subset of 50 participants from the Ausimmune Study were analysed at the four laboratories. Bland-Altman plots were used to visually check agreement between each laboratory against the certified laboratory. Compared with the certified laboratory, serum 25-hydroxyvitamin D concentrations were on average 12.4 nmol/L higher at laboratory A (95% limits of agreement: -17.8,42.6); 12.8 nmol/L higher at laboratory B (95% limits of agreement: 0.8,24.8); and 10.6 nmol/L lower at laboratory C (95% limits of agreement: -48.4,27.1). The prevalence of vitamin D deficiency (defined here as 25-hydroxyvitamin D <50 nmol/L) was 24%, 16%, 12% and 41% at the certified laboratory, and laboratories A, B, and C, respectively. Our results demonstrate considerable differences in the measurement of 25-hydroxyvitamin D concentrations compared with a certified laboratory, even between laboratories using assays based on liquid chromatography-tandem mass spectrometry, which is often considered the gold-standard assay. To ensure accurate and reliable measurement of serum 25-hydroxyvitamin D concentrations, all laboratories should use an accuracy-based quality assurance system and, ideally, comply with international

  5. Analytical Bias in the Measurement of Serum 25-Hydroxyvitamin D Concentrations Impairs Assessment of Vitamin D Status in Clinical and Research Settings.

    PubMed

    Black, Lucinda J; Anderson, Denise; Clarke, Michael W; Ponsonby, Anne-Louise; Lucas, Robyn M

    2015-01-01

    Measured serum 25-hydroxyvitamin D concentrations vary depending on the type of assay used and the specific laboratory undertaking the analysis, impairing the accurate assessment of vitamin D status. We investigated differences in serum 25-hydroxyvitamin D concentrations measured at three laboratories (laboratories A and B using an assay based on liquid chromatography-tandem mass spectrometry and laboratory C using a DiaSorin Liaison assay), against a laboratory using an assay based on liquid chromatography-tandem mass spectrometry that is certified to the standard reference method developed by the National Institute of Standards and Technology and Ghent University (referred to as the 'certified laboratory'). Separate aliquots from the same original serum sample for a subset of 50 participants from the Ausimmune Study were analysed at the four laboratories. Bland-Altman plots were used to visually check agreement between each laboratory against the certified laboratory. Compared with the certified laboratory, serum 25-hydroxyvitamin D concentrations were on average 12.4 nmol/L higher at laboratory A (95% limits of agreement: -17.8,42.6); 12.8 nmol/L higher at laboratory B (95% limits of agreement: 0.8,24.8); and 10.6 nmol/L lower at laboratory C (95% limits of agreement: -48.4,27.1). The prevalence of vitamin D deficiency (defined here as 25-hydroxyvitamin D <50 nmol/L) was 24%, 16%, 12% and 41% at the certified laboratory, and laboratories A, B, and C, respectively. Our results demonstrate considerable differences in the measurement of 25-hydroxyvitamin D concentrations compared with a certified laboratory, even between laboratories using assays based on liquid chromatography-tandem mass spectrometry, which is often considered the gold-standard assay. To ensure accurate and reliable measurement of serum 25-hydroxyvitamin D concentrations, all laboratories should use an accuracy-based quality assurance system and, ideally, comply with international standardisation

  6. Analytical Bias in the Measurement of Serum 25-Hydroxyvitamin D Concentrations Impairs Assessment of Vitamin D Status in Clinical and Research Settings.

    PubMed

    Black, Lucinda J; Anderson, Denise; Clarke, Michael W; Ponsonby, Anne-Louise; Lucas, Robyn M

    2015-01-01

    Measured serum 25-hydroxyvitamin D concentrations vary depending on the type of assay used and the specific laboratory undertaking the analysis, impairing the accurate assessment of vitamin D status. We investigated differences in serum 25-hydroxyvitamin D concentrations measured at three laboratories (laboratories A and B using an assay based on liquid chromatography-tandem mass spectrometry and laboratory C using a DiaSorin Liaison assay), against a laboratory using an assay based on liquid chromatography-tandem mass spectrometry that is certified to the standard reference method developed by the National Institute of Standards and Technology and Ghent University (referred to as the 'certified laboratory'). Separate aliquots from the same original serum sample for a subset of 50 participants from the Ausimmune Study were analysed at the four laboratories. Bland-Altman plots were used to visually check agreement between each laboratory against the certified laboratory. Compared with the certified laboratory, serum 25-hydroxyvitamin D concentrations were on average 12.4 nmol/L higher at laboratory A (95% limits of agreement: -17.8,42.6); 12.8 nmol/L higher at laboratory B (95% limits of agreement: 0.8,24.8); and 10.6 nmol/L lower at laboratory C (95% limits of agreement: -48.4,27.1). The prevalence of vitamin D deficiency (defined here as 25-hydroxyvitamin D <50 nmol/L) was 24%, 16%, 12% and 41% at the certified laboratory, and laboratories A, B, and C, respectively. Our results demonstrate considerable differences in the measurement of 25-hydroxyvitamin D concentrations compared with a certified laboratory, even between laboratories using assays based on liquid chromatography-tandem mass spectrometry, which is often considered the gold-standard assay. To ensure accurate and reliable measurement of serum 25-hydroxyvitamin D concentrations, all laboratories should use an accuracy-based quality assurance system and, ideally, comply with international standardisation

  7. Abnormal parathyroid hormone stimulation of 25-hydroxyvitamin D-1 alpha-hydroxylase activity in the hypophosphatemic mouse. Evidence for a generalized defect of vitamin D metabolism.

    PubMed Central

    Nesbitt, T; Drezner, M K; Lobaugh, B

    1986-01-01

    Abnormal regulation of vitamin D metabolism is a feature of X-linked hypophosphatemic rickets in man and of the murine homologue of the disease in the hypophosphatemic (Hyp)-mouse. We previously reported that mutant mice have abnormally low renal 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) activity for the prevailing degree of hypophosphatemia. To further characterize this defect, we examined whether Hyp-mouse renal 1 alpha-hydroxylase activity responds normally to other stimulatory and inhibitory controls of enzyme function. We studied stimulation by parathyroid hormone (PTH) using: (a) a calcium-deficient (0.02% Ca) diet to raise endogenous PTH; or (b) 24-h continuous infusion of 0.25 IU/h bovine PTH via osmotic minipump. In both cases enzyme activity of identically treated normal mice increased to greater levels than those attained by Hyp-mice. The relative inability of PTH to stimulate 1 alpha-hydroxylase activity is not a function of the hypophosphatemia in the Hyp-mouse since PTH-infused, phosphate-depleted normal mice sustained a level of enzyme activity greater than that of normal and Hyp-mice. In further studies we investigated inhibition of enzyme activity by using: (a) a calcium-loaded (1.2% Ca) diet to suppress endogenous PTH; or (b) 24-h continuous infusion of 0.2 ng/h 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The 1 alpha-hydroxylase activity of normal and Hyp-mice was significantly reduced to similar absolute levels following maintenance on the calcium-loaded diet. Further, infusion of 1,25(OH)2D3 caused a comparable reduction of 1 alpha-hydroxylase activity in normal, Hyp-, and phosphate-depleted normal mice. These observations indicate that the inhibitory control of 1 alpha-hydroxylase by reduced levels of PTH or increased 1,25(OH)2D3 concentrations is intact in the mutants. However, the inability of PTH and hypophosphatemia to stimulate enzyme activity in a manner analogous to that in normal and phosphate-depleted mice indicates

  8. New tritium-release assay for 25-hydroxyvitamin D-1 alpha-hydroxylase

    SciTech Connect

    Brown, A.J.; Perlman, K.; Schnoes, H.K.; DeLuca, H.F.

    1987-08-01

    A new, rapid assay for 1 alpha-hydroxylase has been developed using 25-hydroxy-(1 alpha-/sup 3/H)vitamin D3 as the substrate. Using the solubilized and reconstituted chick 1 alpha-hydroxylase, conversion of this substrate to 1,25-dihydroxyvitamin D3 causes the release of tritium into the aqueous medium. This /sup 3/H/sub 2/O can be easily separated from the labeled substrate by passing the reaction mixture through a reverse-phase silica cartridge. The release of tritium is stereospecific as evidenced by the lack of /sup 3/H/sub 2/O formed when 25-hydroxy-(1 beta-/sup 3/H)vitamin D3 is used as the substrate. In parallel reactions containing the 25-hydroxy-(26,27-/sup 3/H)vitamin D3 substrate, production of labeled 1,25-dihydroxyvitamin D3 was assessed by extraction and high-performance liquid chromatography and found to agree very closely with the amount of /sup 3/H/sub 2/O produced from 25-hydroxy-(1 alpha-/sup 3/H)vitamin D3, validating the accuracy of the new assay. Finally, a major advantage of the tritium-release assay for 1 alpha-hydroxylase is that the results are not affected by further metabolism of the 1,25-dihydroxyvitamin D formed in the incubations.

  9. Transformation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by using Streptomyces sp. strains.

    PubMed Central

    Sasaki, J; Mikami, A; Mizoue, K; Omura, S

    1991-01-01

    To enzymatically synthesize vitamin D derivatives, we screened about 300 Streptomyces sp. strains. Streptomyces sclerotialus FERM BP-1370 and Streptomyces roseoporus FERM BP-1574 were found to have the ability to convert 25-hydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3, respectively, to 1 alpha, 25-dihydroxyvitamin D3. The average rates of 1 alpha hydroxylation of 25-hydroxyvitamin D3 were 6.9 micrograms liter-1 min-1 with FERM BP-1370 and 7.0 micrograms liter-1 min-1 with FERM BP-1574. The specific cytochrome P-450 inhibitors carbon monoxide, SKF-525-A, and metyrapone inhibited the hydroxylation of 1 alpha- and 25-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by FERM BP-1370 and FERM BP-1574. The cytochromes P-450 of these strains were detected by reduced CO difference spectra in the whole-cell suspensions. The appearance of cytochrome P-450 suggests that the cytochromes P-450 of FERM BP-1370 and FERM BP-1574 carry out the hydroxylation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3. PMID:1746944

  10. CYP2R1 Mutations Impair Generation of 25-hydroxyvitamin D and Cause an Atypical Form of Vitamin D Deficiency

    PubMed Central

    Fischer, Philip R.; Singh, Ravinder J.; Roizen, Jeffrey; Levine, Michael A.

    2015-01-01

    Context: Production of the active vitamin D hormone 1,25-dihydroxyvitamin D requires hepatic 25-hydroxylation of vitamin D. The CYP2R1 gene encodes the principal vitamin D 25-hydroxylase in humans. Objective: This study aimed to determine the prevalence of CYP2R1 mutations in Nigerian children with familial rickets and vitamin D deficiency and assess the functional effect on 25-hydroxylase activity. Design and Participants: We sequenced the CYP2R1 gene in subjects with sporadic rickets and affected subjects from families in which more than one member had rickets. Main Outcome Measures: Function of mutant CYP2R1 genes as assessed in vivo by serum 25-hydroxyvitamin D values after administration of vitamin D and in vitro by analysis of mutant forms of the CYP2R1. Results: CYP2R1 sequences were normal in 27 children with sporadic rickets, but missense mutations were identified in affected members of 2 of 12 families, a previously identified L99P, and a novel K242N. In silico analyses predicted that both substitutions would have deleterious effects on the variant proteins, and in vitro studies showed that K242N and L99P had markedly reduced or complete loss of 25-hydroxylase activity, respectively. Heterozygous subjects were less affected than homozygous subjects, and oral administration of vitamin D led to significantly lower increases in serum 25-hydroxyvitamin D in heterozygous than in control subjects, whereas homozygous subjects showed negligible increases. Conclusion: These studies confirm that CYP2R1 is the principal 25-hydroxylase in humans and demonstrate that CYP2R1 alleles have dosage-dependent effects on vitamin D homeostasis. CYP2R1 mutations cause a novel form of genetic vitamin D deficiency with semidominant inheritance. PMID:25942481

  11. Is there a reverse J-shaped association between 25-Hydroxyvitamin D and all-cause mortality? Results from the US Nationally Representative NHANES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The concentration or threshold of 25-Hydroxyvitamin D [25(OH)D] needed to maximally suppress intact serum parathyroid hormone (iPTH) has been suggested as a measure of optimal vitamin D status. Depending upon the definition of maximal suppression of iPTH and the two-phase regression approach used, ...

  12. The reverse J shaped association between serum total 25- hydroxyvitamin D and all-cause mortality: The impact of assay standardization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The impact of standardizing the originally measured serum total 25-hydroxyvitamin D [25(OH)D] values from Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) on the association between 25(OH)D and rate of all-cause mortality was evaluated. Values were standardized to gold ...

  13. UV-dependent production of 25-hydroxyvitamin D{sub 2} in the recombinant yeast cells expressing human CYP2R1

    SciTech Connect

    Yasuda, Kaori; Endo, Mariko; Ikushiro, Shinichi; Kamakura, Masaki; Ohta, Miho; Sakaki, Toshiyuki

    2013-05-03

    Highlights: •We produce 25-hydroxyvitamin D in the recombinant yeast expressing human CYP2R1. •Vitamin D2 is produced in yeast from endogenous ergosterol with UV irradiation. •We produce 25-hydroxyvitamin D2 in the recombinant yeast without added substrate. -- Abstract: CYP2R1 is known to be a physiologically important vitamin D 25-hydroxylase. We have successfully expressed human CYP2R1 in Saccharomyces cerevisiae to reveal its enzymatic properties. In this study, we examined production of 25-hydroxylated vitamin D using whole recombinant yeast cells that expressed CYP2R1. When vitamin D{sub 3} or vitamin D{sub 2} was added to the cell suspension of CYP2R1-expressing yeast cells in a buffer containing glucose and β-cyclodextrin, the vitamins were converted into their 25-hydroxylated products. Next, we irradiated the cell suspension with UVB and incubated at 37 °C. Surprisingly, the 25-hydroxy vitamin D{sub 2} was produced without additional vitamin D{sub 2}. Endogenous ergosterol was likely converted into vitamin D{sub 2} by UV irradiation and thermal isomerization, and then the resulting vitamin D{sub 2} was converted to 25-hydroxyvitamin D{sub 2} by CYP2R1. This novel method for producing 25-hydroxyvitamin D{sub 2} without a substrate could be useful for practical purposes.

  14. An inflection point of serum 25-hydroxyvitamin D for maximal suppression of parathyroid hormone is not evident from multi-site pooled data in children and adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In adults, maximal suppression of serum parathyroid hormone (PTH) has commonly been used to determine the sufficiency of serum 25-hydroxyvitamin D [25(OH) D]. In children and adolescents, the relationship between serum 25(OH) D and PTH is less clear, and most studies reporting a relationship are der...

  15. Three-Phase Model Harmonizes Estimates of the Maximal Suppression of Parathyroid Hormone by 25-Hydroxyvitamin D in Persons 65 Years of Age and Older 1–3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The concentration or threshold of 25-hydroxyvitamin D [25(OH)D] needed to maximally suppress intact serum parathyroid hormone (iPTH) has been suggested as a measure of optimal vitamin D status. Depending upon the definition of maximal suppression of iPTH and the 2-phase regression approach used, 2 d...

  16. Plasma 25-hydroxyvitamin D and progression to diabetes in patients at risk for diabetes: an ancillary analysis in the diabetes prevention program

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We investigated the association between vitamin D status, assessed by plasma 25-hydroxyvitamin D, and risk of incident diabetes. The research design and methods were a prospective observational study with a mean follow-up of 2.7 years in the Diabetes Prevention Program (DPP), a multi-center trial co...

  17. SUMMER AND WINTER VITAMIN D3 LEVELS IN FOUR LEMUR SPECIES HOUSED AT A BRITISH ZOO, WITH REFERENCE TO UVB LEVELS.

    PubMed

    Killick, Rowena; Saunders, Richard; Redrobe, Sharon P

    2015-09-01

    Serum samples were collected from 18 lemurs of four diurnal/cathemeral species housed with outdoor access at Bristol Zoo Gardens (United Kingdom) to test 25-hydroxy-vitamin D3 (25OHD3) levels as part of the veterinary department's preventative health care program. Samples were collected from each lemur in August 2008 (summer) and January 2009 (winter) to examine the effect of season on 25OHD3 levels. The lemurs were fed commercial primate food and a range of fruit and vegetables, and dietary levels of vitamin D3 remained the same throughout the study period. Statistical analysis showed that the lemurs' summer 25OHD3 values (range 26.7 to >150.0 μg/L) were significantly higher than their winter 25OHD3 values (range 11.4-87.1 μg/L). UVB measurements taken during the study period confirmed that UVB levels were significantly higher in summer (mean reading for 1200-1300 GMT time period 153.8 μW/cm2) compared to winter (mean reading for 1200-1300 GMT time period 19.4 μW/cm2). The 25OHD3 levels measured were generally found to be high compared to previously published values from wild (free-ranging) lemurs in Madagascar. The most likely explanation for this was the higher vitamin D3 content of the captive lemurs' diet, as UVB levels at the zoo (latitude 51° north) are substantially lower than those that occur in Madagascar (latitude 12°-26° south). No evidence of vitamin D toxicity or deficiency was found in any of the captive lemurs. The results indicate that vitamin D3 levels in lemurs housed with outdoor access in the United Kingdom and by extension, other regions of similar latitude, vary with seasonal environmental UVB levels, in a similar way to the seasonal variations in vitamin D3 observed in humans living in these regions, but that vitamin D levels in this captive lemur population were adequate compared to wild lemur levels, even in winter.

  18. SUMMER AND WINTER VITAMIN D3 LEVELS IN FOUR LEMUR SPECIES HOUSED AT A BRITISH ZOO, WITH REFERENCE TO UVB LEVELS.

    PubMed

    Killick, Rowena; Saunders, Richard; Redrobe, Sharon P

    2015-09-01

    Serum samples were collected from 18 lemurs of four diurnal/cathemeral species housed with outdoor access at Bristol Zoo Gardens (United Kingdom) to test 25-hydroxy-vitamin D3 (25OHD3) levels as part of the veterinary department's preventative health care program. Samples were collected from each lemur in August 2008 (summer) and January 2009 (winter) to examine the effect of season on 25OHD3 levels. The lemurs were fed commercial primate food and a range of fruit and vegetables, and dietary levels of vitamin D3 remained the same throughout the study period. Statistical analysis showed that the lemurs' summer 25OHD3 values (range 26.7 to >150.0 μg/L) were significantly higher than their winter 25OHD3 values (range 11.4-87.1 μg/L). UVB measurements taken during the study period confirmed that UVB levels were significantly higher in summer (mean reading for 1200-1300 GMT time period 153.8 μW/cm2) compared to winter (mean reading for 1200-1300 GMT time period 19.4 μW/cm2). The 25OHD3 levels measured were generally found to be high compared to previously published values from wild (free-ranging) lemurs in Madagascar. The most likely explanation for this was the higher vitamin D3 content of the captive lemurs' diet, as UVB levels at the zoo (latitude 51° north) are substantially lower than those that occur in Madagascar (latitude 12°-26° south). No evidence of vitamin D toxicity or deficiency was found in any of the captive lemurs. The results indicate that vitamin D3 levels in lemurs housed with outdoor access in the United Kingdom and by extension, other regions of similar latitude, vary with seasonal environmental UVB levels, in a similar way to the seasonal variations in vitamin D3 observed in humans living in these regions, but that vitamin D levels in this captive lemur population were adequate compared to wild lemur levels, even in winter. PMID:26352953

  19. Serum 25-Hydroxyvitamin D and Parathyroid Hormone Levels in Non-Lactating Women with Post-Partum Thyroiditis: The Effect of L-Thyroxine Treatment.

    PubMed

    Krysiak, Robert; Kowalska, Beata; Okopien, Bogusław

    2015-06-01

    Vitamin D deficiency seems to be implicated in the onset and progression of some autoimmune disorders. No previous study has investigated vitamin D homeostasis in post-partum thyroiditis. We compared 25-hydroxyvitamin D and parathyroid hormone (PTH) levels between four groups of non-lactating women who gave birth within 12 months before the beginning of the study: hypothyroid women with post-partum thyroiditis (group A; n = 14), euthyroid females with post-partum thyroiditis (group B; n = 14), women with non-autoimmune hypothyroidism (group C; n = 16) and healthy euthyroid females without thyroid autoimmunity (group D; n = 15). In the second part of the study, groups A and C were treated for 6 months with L-thyroxine. Serum levels of 25-hydroxyvitamin D were lower, while PTH higher in patients with post-partum thyroiditis than in patients without thyroid autoimmunity. They were also lower (25-hydroxyvitamin D) or higher (PTH) in group A than in group B, as well as in group C in comparison with group D. L-thyroxine treatment increased 25-hydroxyvitamin D and reduced PTH levels only in hypothyroid women with post-partum thyroiditis. Baseline levels of 25-hydroxyvitamin D correlated with thyroid antibody titres, thyroid function and circulating PTH levels, while the effect of L-thyroxine on serum levels of this vitamin correlated with the changes in thyroid antibody titres and PTH levels. The results of our study suggest the association of vitamin D status with post-partum thyroiditis and L-thyroxine treatment of this disorder.

  20. Pharmacokinetics of a single oral dose of vitamin D3 (70,000 IU) in pregnant and non-pregnant women

    PubMed Central

    2012-01-01

    Background Improvements in antenatal vitamin D status may have maternal-infant health benefits. To inform the design of prenatal vitamin D3 trials, we conducted a pharmacokinetic study of single-dose vitamin D3 supplementation in women of reproductive age. Methods A single oral vitamin D3 dose (70,000 IU) was administered to 34 non-pregnant and 27 pregnant women (27 to 30 weeks gestation) enrolled in Dhaka, Bangladesh (23°N). The primary pharmacokinetic outcome measure was the change in serum 25-hydroxyvitamin D concentration over time, estimated using model-independent pharmacokinetic parameters. Results Baseline mean serum 25-hydroxyvitamin D concentration was 54 nmol/L (95% CI 47, 62) in non-pregnant participants and 39 nmol/L (95% CI 34, 45) in pregnant women. Mean peak rise in serum 25-hydroxyvitamin D concentration above baseline was similar in non-pregnant and pregnant women (28 nmol/L and 32 nmol/L, respectively). However, the rate of rise was slightly slower in pregnant women (i.e., lower 25-hydroxyvitamin D on day 2 and higher 25-hydroxyvitamin D on day 21 versus non-pregnant participants). Overall, average 25-hydroxyvitamin D concentration was 19 nmol/L above baseline during the first month. Supplementation did not induce hypercalcemia, and there were no supplement-related adverse events. Conclusions The response to a single 70,000 IU dose of vitamin D3 was similar in pregnant and non-pregnant women in Dhaka and consistent with previous studies in non-pregnant adults. These preliminary data support the further investigation of antenatal vitamin D3 regimens involving doses of ≤70,000 IU in regions where maternal-infant vitamin D deficiency is common. Trial registration ClinicalTrials.gov (NCT00938600) PMID:23268736

  1. Seasonal Changes in Vitamin D-Effective UVB Availability in Europe and Associations with Population Serum 25-Hydroxyvitamin D.

    PubMed

    O'Neill, Colette M; Kazantzidis, Andreas; Ryan, Mary J; Barber, Niamh; Sempos, Christopher T; Durazo-Arvizu, Ramon A; Jorde, Rolf; Grimnes, Guri; Eiriksdottir, Gudny; Gudnason, Vilmundur; Cotch, Mary Frances; Kiely, Mairead; Webb, Ann R; Cashman, Kevin D

    2016-01-01

    Low vitamin D status is common in Europe. The major source of vitamin D in humans is ultraviolet B (UVB)-induced dermal synthesis of cholecalciferol, whereas food sources are believed to play a lesser role. Our objectives were to assess UVB availability (Jm(-2)) across several European locations ranging from 35° N to 69° N, and compare these UVB data with representative population serum 25-hydroxyvitamin D (25(OH)D) data from Ireland (51-54° N), Iceland (64° N) and Norway (69° N), as exemplars. Vitamin D-effective UVB availability was modelled for nine European countries/regions using a validated UV irradiance model. Standardized serum 25(OH)D data was accessed from the EC-funded ODIN project. The results showed that UVB availability decreased with increasing latitude (from 35° N to 69° N), while all locations exhibited significant seasonal variation in UVB. The UVB data suggested that the duration of vitamin D winters ranged from none (at 35° N) to eight months (at 69° N). The large seasonal fluctuations in serum 25(OH)D in Irish adults was much dampened in Norwegian and Icelandic adults, despite considerably lower UVB availability at these northern latitudes but with much higher vitamin D intakes. In conclusion, increasing the vitamin D intake can ameliorate the impact of low UVB availability on serum 25(OH)D status in Europe. PMID:27589793

  2. Prevalence and correlates of 25-hydroxyvitamin D deficiency in the Chronic Kidney Disease in Children (CKiD) cohort

    PubMed Central

    McDermott, Kelly; Abraham, Alison G.; Friedman, Lisa Aronson; Johnson, Valerie L.; Kaskel, Frederick J.; Furth, Susan L.; Warady, Bradley A.; Portale, Anthony A.; Melamed, Michal L.

    2016-01-01

    Background Vitamin D plays an important role in the mineral and bone disorder seen in chronic kidney disease (CKD). Deficiency of 25-hydroxyvitamin D (25OHD) is highly prevalent in the adult CKD population. Methods The prevalence and determinants of 25OHD deficiency (defined as a level <20 ng/ml) were examined longitudinally in 506 children in the CKiD cohort. Predictors of secondary hyperparathyroidism and the determinants of 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were also evaluated. Results Deficiency of 25OHD was observed in 28 % of the cohort at enrollment. Significant predictors of 25OHD deficiency were older age, non-white race, higher body mass index, assessment during winter, less often than daily milk intake, non-use of nutritional vitamin D supplement and proteinuria. Lower values of glomerular filtration rate (GFR), serum 25OHD, calcium and higher levels of FGF23 were significant determinants of secondary hyperparathyroidism. Lower GFR, low serum 25OHD, nephrotic-range proteinuria, and high FGF23 levels were significant determinants of serum 1, 25(OH)2 D levels. Conclusions Deficiency of 25OHD is prevalent in children with CKD and is associated with potentially modifiable risk factors such as milk intake, nutritional vitamin D supplement use, and proteinuria. 25OHD deficiency is a risk factor for secondary hyperparathyroidism and decreased serum 1, 25(OH)2D in children with CKD. PMID:26307635

  3. Sunlight and Other Determinants of Circulating 25-Hydroxyvitamin D Levels in Black and White Participants in a Nationwide US Study

    PubMed Central

    Freedman, D. Michal; Cahoon, Elizabeth K.; Rajaraman, Preetha; Major, Jacqueline M.; Doody, Michele M.; Alexander, Bruce H.; Hoffbeck, Richard W.; Kimlin, Michael G.; Graubard, Barry I.; Linet, Martha S.

    2013-01-01

    Circulating 25-hydroxyvitamin D (25(OH)D), a marker for vitamin D status, is associated with bone health and possibly cancers and other diseases; yet, the determinants of 25(OH)D status, particularly ultraviolet radiation (UVR) exposure, are poorly understood. Determinants of 25(OH)D were analyzed in a subcohort of 1,500 participants of the US Radiologic Technologists (USRT) Study that included whites (n = 842), blacks (n = 646), and people of other races/ethnicities (n = 12). Participants were recruited monthly (2008–2009) across age, sex, race, and ambient UVR level groups. Questionnaires addressing UVR and other exposures were generally completed within 9 days of blood collection. The relation between potential determinants and 25(OH)D levels was examined through regression analysis in a random two-thirds sample and validated in the remaining one third. In the regression model for the full study population, age, race, body mass index, some seasons, hours outdoors being physically active, and vitamin D supplement use were associated with 25(OH)D levels. In whites, generally, the same factors were explanatory. In blacks, only age and vitamin D supplement use predicted 25(OH)D concentrations. In the full population, determinants accounted for 25% of circulating 25(OH)D variability, with similar correlations for subgroups. Despite detailed data on UVR and other factors near the time of blood collection, the ability to explain 25(OH)D was modest. PMID:23292956

  4. Circulating vitamin D binding protein, total, free and bioavailable 25-hydroxyvitamin D and risk of colorectal cancer

    PubMed Central

    Ying, Hou-Qun; Sun, Hui-Ling; He, Bang-Shun; Pan, Yu-Qin; Wang, Feng; Deng, Qi-Wen; Chen, Jie; Liu, Xian; Wang, Shu-Kui

    2015-01-01

    Epidemiological investigation have suggested that there is a significantly inverse association between circulating 25-hydroxyvitamin D (25(OH)D) and the risk for developing colorectal cancer (CRC) in humans. However, little is known about the role of vitamin D binding protein (VDBP) in colorectal carcinogenesis. Blood samples were collected from 212 CRC patients and 212 controls matched with age, gender and blood collection time. We used logistic regression to calculate the odds ratios and 95% confidence intervals for further estimation of the association of the quartiles of VDBP, total, free and bioavailable 25(OH)D with CRC risk. The results revealed that there was no significant association between circulating VDBP concentrations and CRC in the present study, and that a negative association existed between total 25(OH)D and the risk of CRC, which was unchanged after adjustment for VDBP. Higher levels of free and bioavailable 25(OH)D were significantly associated with decreased risk of CRC. After stratifying by VDBP, high levels of total, free and bioavailable 25(OH)D were associated significantly with decreased CRC risk among participants with circulating VDBP below the median. These findings indicate that VDBP is not directly associated with the risk of CRC, but it modulates circulating free and bioavailable 25(OH)D concentration. PMID:25609140

  5. Do studies reporting 'U'-shaped serum 25-hydroxyvitamin D-health outcome relationships reflect adverse effects?

    PubMed

    Grant, William B; Karras, Spyridon N; Bischoff-Ferrari, Heike A; Annweiler, Cedric; Boucher, Barbara J; Juzeniene, Asta; Garland, Cedric F; Holick, Michael F

    2016-01-01

    Several reports describe U-shaped 25-hydroxyvitamin D [25(OH)D] concentration-health outcomes, including musculo-skeletal disorders such as falls and fractures, several cancers, cardiovascular disease (CVD), cognitive function, all-cause mortality rates, birth outcomes, allergic reactions, frailty, and some other disorders. This paper reviews reports of U-shaped outcome associations with vitamin D status for evidence of underlying pathophysiological processes, or of confounding, finding that some U-shaped associations appear to be biologically meaningful, but that many could well reflect confounding by factors such as lifestyle, or hypovitaminosis D-related disease onset being masked by self-supplementation that was begun too late to correct developing health problems but before baseline vitamin D status assessment. However, the various U-shaped associations for allergic reactions may be due to vitamin D modulation of the phenotype of the immune response, shifting the Th1-Th2 balance toward Th2 formation. For prostate cancer, there seems to be little effect of 25(OH)D concentration on incidence; however, there is an inverse correlation between 25(OH)D concentration and mortality rates. Future observational studies, and randomized controlled trial data analyses, should include adjustment for data collected on prior long-term vitamin D supplementation and solar UVB exposure, as well as other potential confounders. PMID:27489574

  6. The Association Between Serum 25-Hydroxyvitamin D Concentration and Consumption Frequencies of Vitamin D Food Sources in Korean Adolescents

    PubMed Central

    Yu, Areum; Kim, Jihye; Kwon, Oran; Oh, Se-Young; Kim, Junghyun

    2013-01-01

    The objectives of this study were to investigate the status of vitamin D in Korean adolescents and to determine the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and consumption frequencies of vitamin D food sources by season (June to November and December to May). The subjects were 1,579 adolescents aged 12-18 years participating in the 2008-2009 Korean National Health and Nutrition Examination Survey (KNHANES). Consumption frequencies of vitamin D food sources were estimated by using a qualitative food frequency questionnaire (FFQ). Thirteen food items were selected as vitamin D food sources including beef, egg, mackerel, tuna, yellow corvine, pollack, anchovy, mushroom, milk, yoghurt, ice cream, all fish and dairy products from the FFQ based on previous research. The data was analyzed using proc survey procedures. The deficiency (5.25-12 ng/mL), inadequacy (12-20 ng/mL) and sufficiency (> 20 ng/mL) proportions of serum 25(OH)D from June to November and December to May were 9.9%, 51.4%, 38.7%, and 39.4%, 51.4%, 9.2%, respectively. Mean serum 25(OH)D concentration was positively related to the consumption frequencies of mackerel, anchovy, all fish and milk. These results suggest high proportion (> 61%) of Korean adolescents were vitamin D deficiency or inadequacy, and serum 25(OH)D was associated with the consumption of vitamin D food sources including fish and milk. PMID:23908977

  7. Circulating 25-hydroxyvitamin D and risk of kidney cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

    PubMed

    Gallicchio, Lisa; Moore, Lee E; Stevens, Victoria L; Ahn, Jiyoung; Albanes, Demetrius; Hartmuller, Virginia; Setiawan, V Wendy; Helzlsouer, Kathy J; Yang, Gong; Xiang, Yong-Bing; Shu, Xiao-Ou; Snyder, Kirk; Weinstein, Stephanie J; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Cai, Qiuyin; Campbell, David S; Chen, Yu; Chow, Wong-Ho; Horst, Ronald L; Kolonel, Laurence N; McCullough, Marjorie L; Purdue, Mark P; Koenig, Karen L

    2010-07-01

    Although the kidney is a major organ for vitamin D metabolism, activity, and calcium-related homeostasis, little is known about whether this nutrient plays a role in the development or the inhibition of kidney cancer. To address this gap in knowledge, the authors examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and kidney cancer within a large, nested case-control study developed as part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 775 kidney cancer cases and 775 age-, sex-, race-, and season-matched controls from 8 prospective cohort studies. Overall, neither low nor high concentrations of circulating 25(OH)D were significantly associated with kidney cancer risk. Although the data showed a statistically significant decreased risk for females (odds ratio = 0.31, 95% confidence interval: 0.12, 0.85) with 25(OH)D concentrations of > or =75 nmol/L, the linear trend was not statistically significant and the number of cases in this category was small (n = 14). The findings from this consortium-based study do not support the hypothesis that vitamin D is inversely associated with the risk of kidney cancer overall or with renal cell carcinoma specifically. PMID:20562187

  8. Seasonal Changes in Vitamin D-Effective UVB Availability in Europe and Associations with Population Serum 25-Hydroxyvitamin D

    PubMed Central

    O’Neill, Colette M.; Kazantzidis, Andreas; Ryan, Mary J.; Barber, Niamh; Sempos, Christopher T.; Durazo-Arvizu, Ramon A.; Jorde, Rolf; Grimnes, Guri; Eiriksdottir, Gudny; Gudnason, Vilmundur; Cotch, Mary Frances; Kiely, Mairead; Webb, Ann R.; Cashman, Kevin D.

    2016-01-01

    Low vitamin D status is common in Europe. The major source of vitamin D in humans is ultraviolet B (UVB)-induced dermal synthesis of cholecalciferol, whereas food sources are believed to play a lesser role. Our objectives were to assess UVB availability (Jm−2) across several European locations ranging from 35° N to 69° N, and compare these UVB data with representative population serum 25-hydroxyvitamin D (25(OH)D) data from Ireland (51–54° N), Iceland (64° N) and Norway (69° N), as exemplars. Vitamin D-effective UVB availability was modelled for nine European countries/regions using a validated UV irradiance model. Standardized serum 25(OH)D data was accessed from the EC-funded ODIN project. The results showed that UVB availability decreased with increasing latitude (from 35° N to 69° N), while all locations exhibited significant seasonal variation in UVB. The UVB data suggested that the duration of vitamin D winters ranged from none (at 35° N) to eight months (at 69° N). The large seasonal fluctuations in serum 25(OH)D in Irish adults was much dampened in Norwegian and Icelandic adults, despite considerably lower UVB availability at these northern latitudes but with much higher vitamin D intakes. In conclusion, increasing the vitamin D intake can ameliorate the impact of low UVB availability on serum 25(OH)D status in Europe. PMID:27589793

  9. Do studies reporting ‘U’-shaped serum 25-hydroxyvitamin D–health outcome relationships reflect adverse effects?

    PubMed Central

    Grant, William B.; Karras, Spyridon N.; Bischoff-Ferrari, Heike A.; Annweiler, Cedric; Boucher, Barbara J.; Juzeniene, Asta; Garland, Cedric F.; Holick, Michael F.

    2016-01-01

    ABSTRACT Several reports describe U-shaped 25-hydroxyvitamin D [25(OH)D] concentration–health outcomes, including musculo-skeletal disorders such as falls and fractures, several cancers, cardiovascular disease (CVD), cognitive function, all-cause mortality rates, birth outcomes, allergic reactions, frailty, and some other disorders. This paper reviews reports of U-shaped outcome associations with vitamin D status for evidence of underlying pathophysiological processes, or of confounding, finding that some U-shaped associations appear to be biologically meaningful, but that many could well reflect confounding by factors such as lifestyle, or hypovitaminosis D-related disease onset being masked by self-supplementation that was begun too late to correct developing health problems but before baseline vitamin D status assessment. However, the various U-shaped associations for allergic reactions may be due to vitamin D modulation of the phenotype of the immune response, shifting the Th1-Th2 balance toward Th2 formation. For prostate cancer, there seems to be little effect of 25(OH)D concentration on incidence; however, there is an inverse correlation between 25(OH)D concentration and mortality rates. Future observational studies, and randomized controlled trial data analyses, should include adjustment for data collected on prior long-term vitamin D supplementation and solar UVB exposure, as well as other potential confounders. PMID:27489574

  10. 25-Hydroxyvitamin D Concentration and Leukocyte Telomere Length in Young Adults: Findings From the Northern Finland Birth Cohort 1966.

    PubMed

    Williams, Dylan M; Palaniswamy, Saranya; Sebert, Sylvain; Buxton, Jessica L; Blakemore, Alexandra I F; Hyppönen, Elina; Jarvelin, Marjo-Riitta

    2016-02-01

    Higher vitamin D status, lower adiposity, and longer telomere length are each reportedly associated with lower risk of several chronic diseases and all-cause mortality. However, direct relationships between vitamin D status (measured by circulating 25-hydroxyvitamin D (25(OH)D) concentration), adiposity, and telomere length are not well established. We conducted a cross-sectional analysis of associations of 25(OH)D and body mass index (BMI; weight (kg)/height (m)(2)) with mean relative leukocyte telomere length (LTL) using data gathered on 5,096 participants from Northern Finland Birth Cohort 1966 at age 31 years (1997). 25(OH)D was not associated with LTL in either basic or confounder/mediator-adjusted models. BMI was inversely associated with LTL after adjustment for potential confounding by age, sex, socioeconomic position, physical activity, diet, smoking, alcohol intake, and use of oral contraceptives (per 1-unit increase in BMI, mean difference in LTL = -0.4%, 95% confidence interval: -0.6, -0.2). The BMI-LTL association was also independent of 25(OH)D and was attenuated slightly, but remained, after adjustment for C-reactive protein, a marker of low-grade inflammation (mean difference in LTL = -0.3%, 95% confidence interval -0.6, -0.1). These findings suggest that vitamin D status is unlikely to be an important determinant of LTL, at least by young adulthood. Inflammation may partly mediate associations of adiposity with LTL.

  11. Relationship between 25-Hydroxyvitamin D Levels and Liver Fibrosis as Assessed by Transient Elastography in Patients with Chronic Liver Disease

    PubMed Central

    Ko, Bong Jin; Kim, Young Seok; Kim, Sang Gyune; Park, Jung Hwan; Lee, Sae Hwan; Jeong, Soung Won; Jang, Jae Young; Kim, Hong Soo; Kim, Boo Sung; Kim, Sun Mi; Kim, Young Don; Cheon, Gab Jin; Lee, Bo Ra

    2016-01-01

    Background/Aims Deficiencies of 25-hydroxyvitamin D (25(OH)D) are prevalent in patients with chronic liver disease (CLD). Liver fibrosis is the main determinant of CLD prognosis. The present study was performed to evaluate the correlation between 25(OH)D levels and liver fibrosis as assessed by transient elastography (TE) in patients with compensated CLD. Methods Serum 25(OH)D levels and liver stiffness were determined in a total of 207 patients who were subjected to the following exclusion criteria: patients with decompensated CLD; patients who had malignancies; patients who were taking medications; and patients who were pregnant. Results The most common etiology was chronic hepatitis B (53.1%). Advanced liver fibrosis (defined by TE [≥9.5 kPa]) was present in 75 patients (36.2%). There was a significant correlation between 25(OH)D deficiency and liver stiffness. Based on the multivariate analysis, the following factors were independently associated with advanced liver fibrosis: 25(OH)D deficiency (odds ratio [OR], 3.46; p=0.004), diabetes mellitus (OR, 3.04; p=0.041), and fibrosis-4 index (OR, 2.01; p<0.001). Conclusions Patients with compensated CLD exhibit a close correlation between vitamin D level and liver stiffness as assessed by TE. Vitamin D deficiency was independently associated with advanced liver fibrosis. PMID:27114415

  12. Association of serum 25-hydroxyvitamin D with race/ethnicity and constitutive skin color in urban schoolchildren

    PubMed Central

    Au, Lauren E.; Harris, Susan S.; Dwyer, Johanna T.; Jacques, Paul F.; Sacheck, Jennifer M.

    2015-01-01

    The objective of this study was to determine the extent to which constitutive skin color explains racial/ethnic differences in serum 25-hydroxyvitamin D (25OHD) concentrations in urban schoolchildren. Analysis of covariance (ANCOVA) was used to determine associations of 25OHD with parent-reported race/ethnicity and constitutive skin color as measured by reflectance colorimeter [individual typology angle (ITA°; higher value corresponds to lighter skin)] in 307 Greater Boston schoolchildren aged 9–15 during October–December 2011. Nearly 60% of all children were inadequate in 25OHD (<20 ng/mL). Prevalence of inadequate 25OHD differed by race/ethnicity (p<0.001): white (46.6%), black (74.5%), Hispanic (64.7%), Asian (88.9%), and multi-racial/other (52.7%). Serum 25OHD increased 0.6 ng/mL per 10° increase in ITA° value (p<0.001). The prediction of 25OHD by race/ethnicity was slightly stronger than the prediction by skin color in separate models (R2=0.19, R2=0.16, respectively). Most of the variability in 25OHD in race/ethnicity was due to constitutive skin color in this group of racially diverse US children. PMID:24945426

  13. Determinants of serum 25 hydroxyvitamin D levels in a nationwide cohort of blacks and non-Hispanic whites

    PubMed Central

    Chan, Jacqueline; Jaceldo-Siegl, Karen

    2012-01-01

    Objective To develop algorithms predicting serum 25 hydroxyvitamin D [s25(OH)D] for a large epidemiological study whose subjects come from large geographic areas, are racially diverse and have a wide range in age, skin types, and month of blood sample collection. This will allow a regression calibration approach to determine s25(OH)D levels replacing the more costly method of collection and analysis of blood samples. Study design and setting Questionnaire data from a sub-sample of 236 non-Hispanic whites (whites) and 209 blacks from the widely dispersed Adventist Health Study-2 (n = 96,000) were used to develop prediction algorithms for races separately and combined. A single blood sample was collected from each subject, at different times throughout the year. Results Models with independent variables age, sex, BMI, skin type, UV season, erythemal zone, total dietary vitamin D intake, and sun exposure factor explained 22 and 31% of the variance of s25(OH)D levels in white and black populations, respectively (42% when combined). UV season and erythemal zone determined from measured UV radiation produced models with higher R2 than season and latitude. Conclusion Combining races with a term for race and using variables with measured UV radiation capture the variance in s25(OH)D levels better than analyzing races separately. PMID:20012182

  14. Seasonal Changes in Vitamin D-Effective UVB Availability in Europe and Associations with Population Serum 25-Hydroxyvitamin D.

    PubMed

    O'Neill, Colette M; Kazantzidis, Andreas; Ryan, Mary J; Barber, Niamh; Sempos, Christopher T; Durazo-Arvizu, Ramon A; Jorde, Rolf; Grimnes, Guri; Eiriksdottir, Gudny; Gudnason, Vilmundur; Cotch, Mary Frances; Kiely, Mairead; Webb, Ann R; Cashman, Kevin D

    2016-08-30

    Low vitamin D status is common in Europe. The major source of vitamin D in humans is ultraviolet B (UVB)-induced dermal synthesis of cholecalciferol, whereas food sources are believed to play a lesser role. Our objectives were to assess UVB availability (Jm(-2)) across several European locations ranging from 35° N to 69° N, and compare these UVB data with representative population serum 25-hydroxyvitamin D (25(OH)D) data from Ireland (51-54° N), Iceland (64° N) and Norway (69° N), as exemplars. Vitamin D-effective UVB availability was modelled for nine European countries/regions using a validated UV irradiance model. Standardized serum 25(OH)D data was accessed from the EC-funded ODIN project. The results showed that UVB availability decreased with increasing latitude (from 35° N to 69° N), while all locations exhibited significant seasonal variation in UVB. The UVB data suggested that the duration of vitamin D winters ranged from none (at 35° N) to eight months (at 69° N). The large seasonal fluctuations in serum 25(OH)D in Irish adults was much dampened in Norwegian and Icelandic adults, despite considerably lower UVB availability at these northern latitudes but with much higher vitamin D intakes. In conclusion, increasing the vitamin D intake can ameliorate the impact of low UVB availability on serum 25(OH)D status in Europe.

  15. 25-Hydroxyvitamin D in pregnancy and genome wide cord blood DNA methylation in two pregnancy cohorts (MoBa and ALSPAC).

    PubMed

    Suderman, M; Stene, L C; Bohlin, J; Page, C M; Holvik, K; Parr, C L; Magnus, M C; Håberg, S E; Joubert, B R; Wu, M C; London, S J; Relton, C; Nystad, W

    2016-05-01

    The aim of the study was to investigate whether maternal mid-pregnancy 25-hydroxyvitamin D concentrations are associated with cord blood DNA methylation. DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip, and maternal plasma 25-hydroxyvitamin D was measured in 819 mothers/newborn pairs participating in the Norwegian Mother and Child Cohort (MoBa) and 597 mothers/newborn pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Across 473,731CpG DNA methylation sites in cord blood DNA, none were strongly associated with maternal 25-hydroxyvitamin D after adjusting for multiple tests (false discovery rate (FDR)>0.5; 473,731 tests). A meta-analysis of the results from both cohorts, using the Fisher method for combining p-values, also did not strengthen findings (FDR>0.2). Further exploration of a set of CpG sites in the proximity of four a priori defined candidate genes (CYP24A1, CYP27B1, CYP27A1 and CYP2R1) did not result in any associations with FDR<0.05 (56 tests). In this large genome wide assessment of the potential influence of maternal vitamin D status on DNA methylation, we did not find any convincing associations in 1416 newborns. If true associations do exist, their identification might require much larger consortium studies, expanded genomic coverage, investigation of alternative cell types or measurements of 25-hydroxyvitamin D at different gestational time points. PMID:26953979

  16. 25-Hydroxyvitamin D in pregnancy and genome wide cord blood DNA methylation in two pregnancy cohorts (MoBa and ALSPAC).

    PubMed

    Suderman, M; Stene, L C; Bohlin, J; Page, C M; Holvik, K; Parr, C L; Magnus, M C; Håberg, S E; Joubert, B R; Wu, M C; London, S J; Relton, C; Nystad, W

    2016-05-01

    The aim of the study was to investigate whether maternal mid-pregnancy 25-hydroxyvitamin D concentrations are associated with cord blood DNA methylation. DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip, and maternal plasma 25-hydroxyvitamin D was measured in 819 mothers/newborn pairs participating in the Norwegian Mother and Child Cohort (MoBa) and 597 mothers/newborn pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Across 473,731CpG DNA methylation sites in cord blood DNA, none were strongly associated with maternal 25-hydroxyvitamin D after adjusting for multiple tests (false discovery rate (FDR)>0.5; 473,731 tests). A meta-analysis of the results from both cohorts, using the Fisher method for combining p-values, also did not strengthen findings (FDR>0.2). Further exploration of a set of CpG sites in the proximity of four a priori defined candidate genes (CYP24A1, CYP27B1, CYP27A1 and CYP2R1) did not result in any associations with FDR<0.05 (56 tests). In this large genome wide assessment of the potential influence of maternal vitamin D status on DNA methylation, we did not find any convincing associations in 1416 newborns. If true associations do exist, their identification might require much larger consortium studies, expanded genomic coverage, investigation of alternative cell types or measurements of 25-hydroxyvitamin D at different gestational time points.

  17. Association between Intake of Sugar-Sweetened Beverages and Circulating 25-Hydroxyvitamin D Concentration among Premenopausal Women

    PubMed Central

    Duchaine, Caroline S.; Diorio, Caroline

    2014-01-01

    Intake of sugar-sweetened beverages has increased in North America and seems to have several adverse health effects possibly through decreased circulating 25-hydroxyvitamin D (25(OH)D) concentrations. The aim of this cross-sectional study was to evaluate the association between sugar-sweetened beverages intake and 25(OH)D concentrations among premenopausal women. Intake of sugar-sweetened beverages including colas, other carbonated beverages and sweet fruit drinks was assessed using a validated food frequency questionnaire among 741 premenopausal women. Plasma concentrations of 25(OH)D were quantified by radioimmunoassay. The association between sugar-sweetened beverages intake and 25(OH)D concentrations was evaluated using multivariate generalized linear models and Spearman correlations. A higher intake of colas was associated with lower mean 25(OH)D levels (67.0, 63.7, 64.7 and 58.5 nmol/L for never, <1, 1–3 and >3 servings/week, respectively; r = −0.11 (p = 0.004)). A correlation was observed between intake of other carbonated beverages and 25(OH)D concentrations but was not statistically significant (r = −0.06 (p = 0.10)). No association was observed between intake of sweet fruit drinks and 25(OH)D concentrations. This study suggests that high intake of colas may decrease 25(OH)D levels in premenopausal women. Considering the high consumption of these drinks in the general population and the possible consequences of vitamin D deficiency on health, this finding needs further investigation. PMID:25072269

  18. Serum 25-Hydroxyvitamin D Concentration Is Independently Inversely Associated with Insulin Resistance in the Healthy, Non-Obese Korean Population

    PubMed Central

    Ock, So Young; Ha, Kyoung Hwa; Kim, Bu Kyung; Kim, Hyeon Chang; Shim, Jee-Seon; Lee, Myung Ha; Yoon, Young Me

    2016-01-01

    Background We evaluated the associations between 25-hydroxyvitamin D (25(OH)D) concentrations in serum and insulin resistance in the healthy Korean population. Methods We conducted this cross-sectional analysis in 1,807 healthy Korean people (628 men and 1,179 women) aged 30 to 64 years in the Cardiovascular and Metabolic Disease Etiologic Research Center study. All participants were assessed for 25(OH)D, fasting glucose, and insulin levels, and completed a health examination and lifestyle questionnaire according to standard procedures. Insulin resistance was defined as the homeostasis model assessment insulin resistance higher than the 75 percentile. Results Compared to those in the highest tertile (≥14.3 ng/mL), the odds ratio (OR) for insulin resistance was 1.37 (95% confidence interval [CI], 1.01 to 1.86) for the 1st tertile (<9.7 ng/mL) and 1.19 (95% CI, 0.08 to 1.62) for the 2nd tertile (9.7 to 14.3 ng/mL) after adjusting for age, gender, waist circumference, alcohol consumption, smoking status, physical exercise, season, and cohort. After stratification of the subjects by adiposity, these associations remained only in non-obese subjects (lowest tertile vs. highest tertile, multivariable OR, 1.64; 95% CI, 1.05 to 2.56). Conclusion Serum 25(OH)D has an independent inverse association with insulin resistance in the healthy, non-obese Korean population, even among people with vitamin D insufficiency. PMID:27535642

  19. Higher Serum 25-Hydroxyvitamin D Concentrations Associate with a Faster Recovery of Skeletal Muscle Strength after Muscular Injury

    PubMed Central

    Barker, Tyler; Henriksen, Vanessa T.; Martins, Thomas B.; Hill, Harry R.; Kjeldsberg, Carl R.; Schneider, Erik D.; Dixon, Brian M.; Weaver, Lindell K.

    2013-01-01

    The primary purpose of this study was to identify if serum 25-hydroxyvitamin D (25(OH)D) concentrations predict muscular weakness after intense exercise. We hypothesized that pre-exercise serum 25(OH)D concentrations inversely predict exercise-induced muscular weakness. Fourteen recreationally active adults participated in this study. Each subject had one leg randomly assigned as a control. The other leg performed an intense exercise protocol. Single-leg peak isometric force and blood 25(OH)D, aspartate and alanine aminotransferases, albumin, interferon (IFN)-γ, and interleukin-4 were measured prior to and following intense exercise. Following exercise, serum 25(OH)D concentrations increased (p < 0.05) immediately, but within minutes, subsequently decreased (p < 0.05). Circulating albumin increases predicted (p < 0.005) serum 25(OH)D increases, while IFN-γ increases predicted (p < 0.001) serum 25(OH)D decreases. Muscular weakness persisted within the exercise leg (p < 0.05) and compared to the control leg (p < 0.05) after the exercise protocol. Serum 25(OH)D concentrations inversely predicted (p < 0.05) muscular weakness (i.e., control leg vs. exercise leg peak isometric force) immediately and days (i.e., 48-h and 72-h) after exercise, suggesting the attenuation of exercise-induced muscular weakness with increasing serum 25(OH)D prior to exercise. Based on these data, we conclude that pre-exercise serum 25(OH)D concentrations could influence the recovery of skeletal muscle strength after an acute bout of intense exercise. PMID:23595134

  20. Relationships between n-3 polyunsaturated fatty acid intake, serum 25 hydroxyvitamin D, food consumption, and nutritional status among adolescents.

    PubMed

    Lopes, Mariana P; Giudici, Kelly V; Marchioni, Dirce M; Fisberg, Regina M; Martini, Lígia A

    2015-08-01

    We have hypothesized that higher n-3 polyunsaturated fatty acid (PUFA) intake is associated with better lipid profile, higher 25 hydroxyvitamin D (25(OH)D) serum concentrations, and healthy food consumption and nutritional status. Thus, this study aimed to evaluate the relationships between n-3 PUFA intake, serum 25(OH)D, lipid profile, nutritional status, and food consumption among adolescents. A total of 198 Brazilian adolescents (51% male), with mean age of 16.3 ± 1.4 years, were enrolled in this cross-sectional study. Blood was collected for 25(OH)D and lipid profile serum measurement. Weight and height were measured, and food consumption was accessed by a 24-hour food record (n = 69). Analysis of variance, the Student t test, and Pearson correlation were performed using SPSS software (SPSS, Chicago, IL, USA). The prevalence of vitamin D inadequacy (25(OH)D, <30 ng/mL) was 71.7%. Serum 25(OH)D negatively correlated with body mass index (r = -0.294; P < .0001) and positively correlated with high-density lipoprotein cholesterol (r = 0.323; P < .0001). N-3 PUFA intake negatively correlated with body mass index (r = -0.286; P = .017), total cholesterol (r = -0.292; P = .015), and low-density lipoprotein cholesterol (r = -0.333; P = .005) and positively correlated with the intake of fat meats and eggs (r = 0.391; P = .006), vegetable proteins (r = 0.297; P = .048), fats/oils (r = 0.574; P < .001), and refined cereals (r = 0.351; P = .006). Vitamin D status and n-3 PUFA intake were related with better nutritional status and favorable lipid profile. Food groups usually found in Brazilian traditional meals (characterized by rice, beans, meat, and vegetables) were associated with higher n-3 PUFA intake, which may contribute to prevent the development of noncommunicable diseases in adolescence and adulthood. PMID:26094211

  1. Dietary phosphorus transcriptionally regulates 25-hydroxyvitamin D-1alpha-hydroxylase gene expression in the proximal renal tubule.

    PubMed

    Zhang, Martin Y H; Wang, Xuemei; Wang, Jonathan T; Compagnone, Nathalie A; Mellon, Synthia H; Olson, Jean L; Tenenhouse, Harriet S; Miller, Walter L; Portale, Anthony A

    2002-02-01

    Synthesis of the hormone 1,25-dihydroxyvitamin D, the biologically active form of vitamin D, occurs in the kidney and is catalyzed by the mitochondrial cytochrome P450 enzyme, 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase). We sought to characterize the effects of changes in dietary phosphorus on the kinetics of renal mitochondrial 1alpha-hydroxylase activity and the renal expression of P450c1alpha and P450c24 mRNA, to localize the nephron segments involved in such regulation, and to determine whether transcriptional mechanisms are involved. In intact mice, restriction of dietary phosphorus induced rapid, sustained, approximately 6- to 8-fold increases in renal mitochondrial 1alpha-hydroxylase activity and renal P450c1alpha mRNA abundance. Immunohistochemical analysis of renal sections from mice fed the control diet revealed the expression of 1alpha-hydroxylase protein in the proximal convoluted and straight tubules, epithelial cells of Bowman's capsule, thick ascending limb of Henle's loop, distal tubule, and collecting duct. In mice fed a phosphorus-restricted diet, immunoreactivity was significantly increased in the proximal convoluted and proximal straight tubules and epithelial cells of Bowman's capsule, but not in the distal nephron. Dietary phosphorus restriction induced a 2-fold increase in P450c1alpha gene transcription, as shown by nuclear run-on assays. Thus, the increase in renal synthesis of 1,25-dihydroxyvitamin D induced in normal mice by restricting dietary phosphorus can be attributed to an increase in the renal abundance of P450c1alpha mRNA and protein. The increase in P450c1alpha gene expression, which occurs exclusively in the proximal renal tubule, is due at least in part to increased transcription of the P450c1alpha gene.

  2. 25-Hydroxyvitamin D level does not reflect intestinal calcium absorption: an assay using strontium as a surrogate marker.

    PubMed

    Camargo, Marília Brasilio Rodrigues; Vilaça, Tatiane; Hayashi, Lilian Fukusima; Rocha, Olguita G Ferreira; Lazaretti-Castro, Marise

    2015-05-01

    There is conflicting evidence as to the optimal serum 25-hydroxyvitamin D [25(OH)D] concentration for intestinal calcium absorption (Abs-Ca). Our purpose was to assess the relationship between vitamin D status and Abs-Ca in postmenopausal women. Fifty volunteers with low bone mass were grouped according to their serum 25(OH)D concentration as follows: mild deficient, <50 nmol/L (DEF) and sufficient, ≥75 nmol/L (SUF). The subjects were submitted to an oral strontium overload test to assess their Abs-Ca. Fasting blood samples were obtained to perform the relevant hormonal and biochemical tests. After the subjects received the test solution, blood samples were drawn at 30, 60, 120, and 240 min to determine the strontium concentrations. Abs-Ca was indirectly expressed as the area under the serum strontium concentration curve (AUC). A repeated measures ANOVA was performed to determine the differences among the groups. Pearson's correlation and multiple linear regression analysis were used to study the associations between the variables. The mean 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations differed between the groups (SUF vs. DEF) as follows: 98.7 ± 18.2 vs. 38.4 ± 8.5 nmol/L (p < 0.001) and 36.2 ± 10.2 vs. 24.9 ± 4.6 pg/mL (p < 0.001), respectively. There was no statistically significant difference between the groups for parathyroid hormone and AUC. Only 1,25(OH)2D influenced the strontium absorption in the last 2 h of the test. In the studied population, no correlation between levels of 25(OH)D and Abs-Ca was found. Only 1,25(OH)2D influenced Abs-Ca as measured by a strontium absorption test.

  3. A prospective study of serum 25-hydroxyvitamin d levels and mortality among African Americans and non-African Americans.

    PubMed

    Signorello, Lisa B; Han, Xijing; Cai, Qiuyin; Cohen, Sarah S; Cope, Elizabeth L; Zheng, Wei; Blot, William J

    2013-01-15

    The beneficial biologic effects attributed to vitamin D suggest a potential to influence overall mortality. Evidence addressing this hypothesis is limited, especially for African Americans who have a high prevalence of vitamin D insufficiency. The authors conducted a nested case-control study within the prospective Southern Community Cohort Study to relate baseline serum levels of 25-hydroxyvitamin D (25(OH)D) with subsequent mortality. Cases were 1,852 participants who enrolled from 2002 to 2009 and died >12 months postenrollment. Controls (n = 1,852) were matched on race, sex, age, enrollment site, and blood collection date. The odds ratios for quartile 1 (<10.18 ng/mL) versus quartile 4 (>21.64 ng/mL) levels of 25(OH)D were 1.60 (95% confidence interval (CI): 1.20, 2.14) for African Americans and 2.11 (95% CI: 1.39, 3.21) for non-African Americans. The effects were strongest for circulatory disease death, where quartile 1 versus quartile 4 odds ratios were 2.53 (95% CI: 1.44, 4.46) and 3.25 (95% CI: 1.33, 7.93) for African Americans and non-African Americans, respectively. The estimated odds of total mortality were minimized in the 25(OH)D range of 35-40 ng/mL. These findings provide support for the hypothesis that vitamin D status may have an important influence on mortality for both African Americans and non-African Americans.

  4. 25-Hydroxyvitamin D Concentration and Leukocyte Telomere Length in Young Adults: Findings From the Northern Finland Birth Cohort 1966

    PubMed Central

    Williams, Dylan M.; Palaniswamy, Saranya; Sebert, Sylvain; Buxton, Jessica L.; Blakemore, Alexandra I. F.; Hyppönen, Elina; Jarvelin, Marjo-Riitta

    2016-01-01

    Higher vitamin D status, lower adiposity, and longer telomere length are each reportedly associated with lower risk of several chronic diseases and all-cause mortality. However, direct relationships between vitamin D status (measured by circulating 25-hydroxyvitamin D (25(OH)D) concentration), adiposity, and telomere length are not well established. We conducted a cross-sectional analysis of associations of 25(OH)D and body mass index (BMI; weight (kg)/height (m)2) with mean relative leukocyte telomere length (LTL) using data gathered on 5,096 participants from Northern Finland Birth Cohort 1966 at age 31 years (1997). 25(OH)D was not associated with LTL in either basic or confounder/mediator-adjusted models. BMI was inversely associated with LTL after adjustment for potential confounding by age, sex, socioeconomic position, physical activity, diet, smoking, alcohol intake, and use of oral contraceptives (per 1-unit increase in BMI, mean difference in LTL = −0.4%, 95% confidence interval: −0.6, −0.2). The BMI-LTL association was also independent of 25(OH)D and was attenuated slightly, but remained, after adjustment for C-reactive protein, a marker of low-grade inflammation (mean difference in LTL = −0.3%, 95% confidence interval −0.6, −0.1). These findings suggest that vitamin D status is unlikely to be an important determinant of LTL, at least by young adulthood. Inflammation may partly mediate associations of adiposity with LTL. PMID:26797572

  5. The association between serum 25-hydroxyvitamin D level and recurrent falls in the elderly population: a cohort study

    PubMed Central

    Ghafouri, Hamed Basir; Zare, Morteza; Bazrafshan, Azam; Modirian, Ehsan; Mousavi, Afkham; Abazarian, Niloofar

    2016-01-01

    Introduction Serum vitamin D concentration is a major contributing factor for increasing the risk of fall and fall-related injuries in older adults. However, when prescribed and supplemented for these populations, the outcomes are controversial, and in several cases no improvement has been reported in reducing the risk of recurrent falls. This study aimed to examine the association between serum vitamin D concentration and recurrent falls in Iranian older adults. Methods This cohort study was conducted in the emergency departments of two university hospitals. A cohort of 82 elderly participants aged over 60 and suffered from an unintentional episode of falling was evaluated six months after their first ED visit. A structured, self-administered checklist was developed to obtain the participants’ demographic and clinical information. Participants also were asked about any recurrent fall experience during follow-up. Results The mean (SD) age of the study population was 75 (8). Over half of the participants were male (57.3%). The mean (median) serum 25-hydroxyvitamin D (25 (OH)D) concentration was 38 (34) ng/ml. Mean serum 25(OH)D levels varied slightly between gender groups (p=0.450). An inverse but insignificant association was found between the age of participants and their serum 25(OH)D levels (r=−0.03, p=0.7). A small but insignificant association also was found between the mean serum 25(OH)D level and the number of recurrent falls in elderly patients irrespective of their age, gender, or physical activity groups (OR=1.008, p=0.992). Conclusion In contrast to previous studies, no significant association of serum 25(OH)D concentration was found with recurrent falls in Iranian older adults.

  6. Associations of vitamin D intake with 25-hydroxyvitamin D in overweight and racially/ethnically diverse US children.

    PubMed

    Au, Lauren E; Rogers, Gail T; Harris, Susan S; Dwyer, Johanna T; Jacques, Paul F; Sacheck, Jennifer M

    2013-11-01

    Overweight children and minorities are at risk of vitamin D deficiency. Little information exists on whether overweight children and minorities who do not meet dietary vitamin D recommendations are at risk for low 25-hydroxyvitamin D (25OHD) status. Vitamin D intake from foods and dietary supplements was estimated in 3,310 children/adolescents who were examined as part of the 2005-2006 National Health and Nutrition Examination Survey. Weight status was dichotomized into healthy weight or overweight/obese. Parent-reported race/ethnicity was categorized as non-Hispanic white, non-Hispanic black, Mexican American, or other. Adjusted logistic regression was used to determine whether children who did not achieve the Estimated Average Requirement (EAR) were at increased risk for inadequate 25OHD. Nearly 75% of children failed to meet the EAR. Overall, not meeting the EAR was associated with inadequate 25OHD (odds ratio=2.5; 95% CI 1.4 to 4.5). However, this association differed by weight status (P=0.02) and race/ethnicity (P=0.02). Overweight/obese children who failed to meet the EAR were five times more likely to be at risk for inadequate 25OHD than overweight/obese children who met it (95% CI 2.0 to 12.7; P<0.001). Non-Hispanic blacks with intakes below the EAR were nearly four times more likely to be at risk for inadequate 25OHD than those who met the EAR (95% CI 1.5 to 9.7; P<0.01). The majority of US children failed to meet current vitamin D recommendations. Overweight/obese and non-Hispanic black children were especially likely to be at risk for inadequate 25OHD when not consuming the EAR. PMID:23916971

  7. Circulating 25-hydroxyvitamin D Levels and Frailty Status in Older Men: The Osteoporotic Fractures in Men Study

    PubMed Central

    Ensrud, Kristine E.; Blackwell, Terri L.; Cauley, Jane A.; Cummings, Steven R.; Barrett-Connor, Elizabeth; Dam, Thuy-Tien L.; Hoffman, Andrew R.; Shikany, James M.; Lane, Nancy E.; Stefanick, Marcia L.; Orwoll, Eric S.; Cawthon, Peggy M.

    2012-01-01

    Objectives To determine the cross-sectional and longitudinal associations of 25-hydroxyvitamin D (25(OH)D) levels with frailty status in older men. Design Prospective cohort study Setting Six U.S. community-based centers Participants 1606 men aged ≥65 years Measurements 25(OH)D (liquid chromatography-tandem mass spectroscopy) and frailty status (criteria similar to those used in the Cardiovascular Health Study) measured at baseline; frailty status assessment repeated an average of 4.6 years later. Frailty status classified as robust, intermediate stage, or frail at baseline; and robust, intermediate stage, frail, or dead at follow-up. Results After adjusting for multiple potential confounders, men with 25(OH)D levels <20.0 ng/mL had a 1.5-fold higher odds (multivariate odds ratio (MOR) 1.47, 95% confidence interval (CI) 1.07–2.02) of greater frailty status at baseline as compared with men with 25(OH)D levels ≥30.0 ng/mL (referent group), while frailty status was similar between men with 25(OH)D levels 20.0–29.9 ng/mL and those with 25(OH)D levels ≥30 ng/mL (MOR 1.02, 95% CI 0.78–1.32). However, among 1267 men not classified as frail at baseline, there was no association between lower baseline 25(OH)D level and odds of greater frailty status at the 4.6 year follow-up. Findings were unchanged when 25(OH)D was expressed in quartiles or as a continuous variable. Conclusion Lower levels of 25(OH)D (levels <20 ng/mL) among community dwelling older men were independently associated with greater evidence of frailty at baseline, but did not predict increased risk of greater frailty status at 4.6 years. PMID:21226680

  8. Circulating levels of 25-hydroxyvitamin D and risk of breast cancer: a nested case-control study

    PubMed Central

    2013-01-01

    Introduction Experimental evidence suggests a protective role for circulating 25-hydroxyvitamin D (25(OH)D) in breast cancer development, but the results of epidemiological studies have been inconsistent. Methods We conducted a case-control study nested within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Mammary Screening Cohort. Blood samples were collected at enrollment, and women were followed up for breast cancer ascertainment. In total, 1,585 incident breast cancer cases were individually-matched to 2,940 controls. Of these subjects, 678 cases and 1,208 controls contributed two repeat blood samples, at least one year apart. Circulating levels of 25(OH)D were measured, and multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Results No association was observed between circulating levels of 25(OH)D and overall breast cancer risk (multivariate-adjusted model OR = 0.94, 95% CI = 0.76-1.16 for the highest vs. lowest quintile, ptrend = 0.30). The temporal reliability of 25(OH)D measured in repeat blood samples was high (intraclass correlation coefficients for season-adjusted 25(OH)D > 0.70). An inverse association between 25(OH)D levels and breast cancer risk was observed among women who were ≤ 45 years of age (ORQ5-Q1 = 0.48, 95% CI = 0.30-0.79, ptrend = 0.01) or premenopausal at enrollment (ORQ5-Q1 = 0.67, 95% CI = 0.48-0.92, ptrend = 0.03). Conclusions Circulating 25(OH)D levels were not associated with breast cancer risk overall, although we could not exclude the possibility of a protective effect in younger women. Recommendations regarding vitamin D supplementation should be based on considerations other than breast cancer prevention. PMID:23442740

  9. The Effect of Serum 25-Hydroxyvitamin D on Elevated Homocysteine Concentrations in Participants of a Preventive Health Program

    PubMed Central

    Pham, Truong-Minh; Ekwaru, John Paul; Mastroeni, Silmara S.; Mastroeni, Marco F.; Loehr, Sarah A.; Veugelers, Paul J.

    2016-01-01

    Both lower serum 25-hydroxyvitamin D [25(OH)D] and elevated homocysteine concentrations are potential risk factors for cardiovascular disease (CVD). A recent analysis of the National Health and Nutrition Examination Survey reported an inverse association of serum 25(OH)D with homocysteine, however, the longitudinal relationship has yet to be investigated. We hypothesized and examined whether a temporal increase in 25(OH)D concentrations is paralleled by a reduction in the risk for elevated homocysteine. We analyzed data of 4475 participants with repeated assessments of serum 25(OH)D and homocysteine concentrations who enrolled in a preventive health program that encourages vitamin D supplementation and monitors serum 25(OH)D and homocysteine concentrations. We defined elevated homocysteine as concentrations greater than 13 micromoles per liter. Logistic regression was applied to assess the association of temporal changes in serum 25(OH)D with the risk of elevated homocysteine. We observed an inverse gradient whereby greater increases in 25(OH)D concentrations were associated with a lower prevalence of elevated homocysteine. Relative to those without temporal increases in 25(OH)D, participants who showed improvements in their serum 25(OH)D concentrations of “<25”, “25–50”, “50–75”, and “≥75” nanomoles per liter at follow up were 0.92 (95% confidence interval: 0.62–1.37), 0.52 (0.33–0.80), 0.34 (0.20–0.58), and 0.32 (0.19–0.54) times as likely to have elevated homocysteine, respectively. These observations suggest that temporal improvements in vitamin D status reduce serum homocysteine concentrations, and therefore may potentially contribute to the primary prevention of CVD. PMID:27548258

  10. Plasma 25-Hydroxyvitamin D Is Related to Protein Signaling Involved in Glucose Homeostasis in a Tissue-Specific Manner

    PubMed Central

    Parker, Lewan; Levinger, Itamar; Mousa, Aya; Howlett, Kirsten; de Courten, Barbora

    2016-01-01

    Vitamin D has been suggested to play a role in glucose metabolism. However, previous findings are contradictory and mechanistic pathways remain unclear. We examined the relationship between plasma 25-hydroxyvitamin D (25(OH)D), insulin sensitivity, and insulin signaling in skeletal muscle and adipose tissue. Seventeen healthy adults (Body mass index: 26 ± 4; Age: 30 ± 12 years) underwent a hyperinsulinemic-euglycemic clamp, and resting skeletal muscle and adipose tissue biopsies. In this cohort, the plasma 25(OH)D concentration was not associated with insulin sensitivity (r = 0.19, p = 0.56). However, higher plasma 25(OH)D concentrations correlated with lower phosphorylation of glycogen synthase kinase-3 (GSK-3) αSer21 and βSer9 in skeletal muscle (r = −0.66, p = 0.015 and r = −0.53, p = 0.06, respectively) and higher GSK-3 αSer21 and βSer9 phosphorylation in adipose tissue (r = 0.82, p < 0.01 and r = 0.62, p = 0.042, respectively). Furthermore, higher plasma 25(OH)D concentrations were associated with greater phosphorylation of both protein kinase-B (AktSer473) (r = 0.78, p < 0.001) and insulin receptor substrate-1 (IRS-1Ser312) (r = 0.71, p = 0.01) in adipose tissue. No associations were found between plasma 25(OH)D concentration and IRS-1Tyr612 phosphorylation in skeletal muscle and adipose tissue. The divergent findings between muscle and adipose tissue with regard to the association between 25(OH)D and insulin signaling proteins may suggest a tissue-specific interaction with varying effects on glucose homeostasis. Further research is required to elucidate the physiological relevance of 25(OH)D in each tissue. PMID:27754361

  11. Narrow-band ultraviolet B treatment boosts serum 25-hydroxyvitamin D in patients with psoriasis on oral vitamin D supplementation.

    PubMed

    Ala-Houhala, Meri J; Karppinen, Toni; Vähävihu, Katja; Kautiainen, Hannu; Dombrowski, Yvonne; Snellman, Erna; Schauber, Jürgen; Reunala, Timo

    2014-03-01

    A course of treatment with narrow-band ultraviolet B (NB-UVB) improves psoriasis and increases serum 25-hydroxyvitamin D (25(OH)D). In this study 12 patients with psoriasis who were supplemented with oral cholecalciferol, 20 µg daily, were given a course of NB-UVB and their response measured. At baseline, serum 25(OH)D was 74.14 ± 22.9 nmol/l. At the 9th exposure to NB-UVB 25(OH)D had increased by 13.2 nmol/l (95% confidence interval (95% CI) 7.2-18.4) and at the 18th exposure by 49.4 nmol/l (95% CI 35.9-64.6) above baseline. Psoriasis Area Severity Index score improved from 8.7 ± 3.5 to 4.5 ± 2.0 (p < 0.001). At baseline, psoriasis lesions showed low vitamin D metabolizing enzyme (CYP27A1, CYP27B1) and high human β-defensin-2 mRNA expression levels compared with those of the healthy subjects. In conclusion, NB-UVB treatment significantly increases serum 25(OH)D in patients with psoriasis who are taking oral vitamin D supplementation, and the concentrations remain far from the toxicity level. Healing psoriasis lesions show similar mRNA expression of vitamin D metabolizing enzymes, but higher antimicrobial peptide levels than NB-UVB-treated skin in healthy subjects.

  12. Relationships between n-3 polyunsaturated fatty acid intake, serum 25 hydroxyvitamin D, food consumption, and nutritional status among adolescents.

    PubMed

    Lopes, Mariana P; Giudici, Kelly V; Marchioni, Dirce M; Fisberg, Regina M; Martini, Lígia A

    2015-08-01

    We have hypothesized that higher n-3 polyunsaturated fatty acid (PUFA) intake is associated with better lipid profile, higher 25 hydroxyvitamin D (25(OH)D) serum concentrations, and healthy food consumption and nutritional status. Thus, this study aimed to evaluate the relationships between n-3 PUFA intake, serum 25(OH)D, lipid profile, nutritional status, and food consumption among adolescents. A total of 198 Brazilian adolescents (51% male), with mean age of 16.3 ± 1.4 years, were enrolled in this cross-sectional study. Blood was collected for 25(OH)D and lipid profile serum measurement. Weight and height were measured, and food consumption was accessed by a 24-hour food record (n = 69). Analysis of variance, the Student t test, and Pearson correlation were performed using SPSS software (SPSS, Chicago, IL, USA). The prevalence of vitamin D inadequacy (25(OH)D, <30 ng/mL) was 71.7%. Serum 25(OH)D negatively correlated with body mass index (r = -0.294; P < .0001) and positively correlated with high-density lipoprotein cholesterol (r = 0.323; P < .0001). N-3 PUFA intake negatively correlated with body mass index (r = -0.286; P = .017), total cholesterol (r = -0.292; P = .015), and low-density lipoprotein cholesterol (r = -0.333; P = .005) and positively correlated with the intake of fat meats and eggs (r = 0.391; P = .006), vegetable proteins (r = 0.297; P = .048), fats/oils (r = 0.574; P < .001), and refined cereals (r = 0.351; P = .006). Vitamin D status and n-3 PUFA intake were related with better nutritional status and favorable lipid profile. Food groups usually found in Brazilian traditional meals (characterized by rice, beans, meat, and vegetables) were associated with higher n-3 PUFA intake, which may contribute to prevent the development of noncommunicable diseases in adolescence and adulthood.

  13. Dietary products consumption in relation to serum 25-hydroxyvitamin D and selenium level in Saudi children and adults

    PubMed Central

    Al-Daghri, Nasser M; Al-Attas, Omar; Yakout, Sobhy; Aljohani, Naji; Al-Fawaz, Hanan; Alokail, Majed S

    2015-01-01

    Vitamin D deficiency is a global health threat that has been associated with several chronic diseases. Selenium is an essential trace element because of role in major metabolic processes, immune function, thyroid hormone metabolism, male infertility, neoplasms and cardiovascular disease. We aimed to investigate for the first time in the Saudi population the association between vitamin D and selenium status with various dietary products consumption. A total of 259 children and 95 adults were included in this cross-sectional study. We estimated the consumption frequencies of various dietary food products using a qualitative food frequency questionnaire (FFQ) and also measured serum levels of 25-hydroxyvitamin D and selenium. Associations between variables of interest were assessed. Vitamin D deficiency and insufficiency were observed in 80% of the boys, 90% of the girls, 64% of men and 50% of women. Modest associations were found between mean serum 25 (OH) D concentration and consumption frequencies of fresh milk in children (r=0.11; P<0.05), more specifically in girls (r=0.12; P<0.05), and to the overall consumption of dairy products in women (r=0.12; P<0.05). Vitamin D status was also inversely associated with selenium in adults (r=-0.43; P<0.05). There was a significant correlation between delta changes of serum selenium, triglycerides and HDL levels (P-values <0.05). Vitamin D and selenium levels are modestly associated with dietary products consumption. Changes in selenium levels were associated with increased serum triglyceride levels, indicating a potential biomarker for cardiovascular risk and dyslipidemia. The widespread vitamin D deficiency observed in the present study highlight the need for adequate fortification of dairy products. PMID:25785131

  14. Serum 25-hydroxyvitamin D response to vitamin D3 supplementation 50,000 IU monthly in youth with HIV-1 infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Context: Vitamin D deficiency and insufficiency occur frequently in youth with HIV infection, particularly among those receiving the antiretroviral drug efavirenz. Optimal vitamin D dosing for treatment is unclear. Objective: Measure change in 25-hydroxy vitamin D (25-OHD) concentration from basel...

  15. Oral supplementation with 25(OH)D3 versus vitamin D3: effects on 25(OH)D levels, lower extremity function, blood pressure, and markers of innate immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To test the effect of 25(OH)D3 (HyD) compared to vitamin D3 on serum 25-hydroxyvitamin D levels (25(OH)D), lower extremity function, blood pressure, and markers of innate immunity. Twenty healthy postmenopausal women with an average 25(OH)D level of 13.23.9 ng/mL (meanSD) and a mean age of 61.57.2 y...

  16. Serum 25-hydroxyvitamin-D responses to multiple UV exposures from solaria: inferences for exposure to sunlight.

    PubMed

    McKenzie, Richard; Scragg, Robert; Liley, Ben; Johnston, Paul; Wishart, John; Stewart, Alistair; Prematunga, Roshani

    2012-07-01

    We investigate the relationship between blood serum 25-hydroxyvitamin D (25(OH)D) and UV exposure from two artificial sources. We then use the results to test the validity of the action spectrum for vitamin D production, and to infer the production from summer and winter sunlight. The results are based on a two-arm randomised clinical trial of biweekly UV exposure for 12 weeks using two different types of dermatological booths: one emitting primarily UV-A radiation, and the other emitting primarily UV-B radiation (booth A and booth B respectively). In terms of the vitamin D production per unit erythema, one of the booths mimics summer noon sunlight, while the other mimics winter noon sunlight. Blood samples were taken before and after the exposures. For all participants, the phototherapy booth treatments arrested the usual wintertime decline in 25(OH)D, and for most the treatments from either booth resulted in significant increases. The increases were highly non-linear and there was a high degree of variability in 25(OH)D and its response to UV from person to person. By the end of the 12 week period, the mean increase was >30 nmol l(-1) from a cumulative exposure of 17 SED from the UV-A booth, and twice that for the UV-B booth for which the cumulative exposure was 268 SED. Assuming a logarithmic relationship between UV and vitamin D, the results for the two booths show no obvious inconsistency in the action spectrum for pre-vitamin D production. However, further measurements with similar exposures from each booth are required to confirm its validity. A model was developed to describe the increases in serum 25(OH)D resulting from the UV exposures, which differed markedly between the two booths. The deduced initial rate of increase of 25(OH)D was approximately 5 nmol l(-1) per SED. From the large increases in 25(OH)D from each booth, along with knowledge of the spectral distribution of sunlight and assuming the currently-accepted action spectrum for photo

  17. Serum 25-Hydroxyvitamin D Status and Longitudinal Changes in Weight and Waist Circumference: Influence of Genetic Predisposition to Adiposity.

    PubMed

    Larsen, Sofus C; Ängquist, Lars; Moldovan, Max; Huikari, Ville; Sebert, Sylvain; Cavadino, Alana; Ahluwalia, Tarunveer Singh; Skaaby, Tea; Linneberg, Allan; Husemoen, Lise Lotte N; Toft, Ulla; Pedersen, Oluf; Hansen, Torben; Herzig, Karl-Heinz; Jarvelin, Marjo-Riitta; Power, Chris; Hyppönen, Elina; Heitmann, Berit L; Sørensen, Thorkild I A

    2016-01-01

    Studies of the relationship between serum 25-hydroxyvitamin D (25(OH)D) and changes in measures of adiposity have shown inconsistent results, and interaction with genetic predisposition to obesity has rarely been examined. We examined whether 25(OH)D was associated with subsequent annual changes in body weight (ΔBW) or waist circumference (ΔWC), and whether the associations were modified by genetic predisposition to a high BMI, WC or waist-hip ratio adjusted for BMI (WHRBMI). The study was based on 10,898 individuals from the Danish Inter99, the 1958 British Birth Cohort and the Northern Finland Birth Cohort 1966. We combined 42 adiposity-associated Single Nucleotide Polymorphisms (SNPs) into four scores indicating genetic predisposition to BMI, WC and WHRBMI, or all three traits combined. Linear regression was used to examine the association between serum 25(OH)D and ΔBW or ΔWC, SNP-score × 25(OH)D interactions were examined, and results from the individual cohorts were meta-analyzed. In the meta-analyses, we found no evidence of an association between 25(OH)D and ΔBW (-9.4 gram/y per 10 nmol/L higher 25(OH)D [95% CI: -23.0, +4.3; P = 0.18]) or ΔWC (-0.06 mm/y per 10 nmol/L higher 25(OH)D [95% CI: -0.17, +0.06; P = 0.33]). Furthermore, we found no statistically significant interactions between the four SNP-scores and 25(OH)D in relation to ΔBW or ΔWC. Thus, in view of the narrow CIs, our results suggest that an association between 25(OH)D and changes in measures of adiposity is absent or marginal. Similarly, the study provided evidence that there is either no or very limited dependence on genetic predisposition to adiposity. PMID:27077659

  18. Determinants of serum 25-hydroxyvitamin D concentration in Finnish children: the Physical Activity and Nutrition in Children (PANIC) study.

    PubMed

    Soininen, Sonja; Eloranta, Aino-Maija; Lindi, Virpi; Venäläinen, Taisa; Zaproudina, Nina; Mahonen, Anitta; Lakka, Timo A

    2016-03-28

    We studied vitamin D intake, serum 25-hydroxyvitamin D (S-25(OH)D) concentration, determinants of S-25(OH)D and risk factors for S-25(OH)D <50 nmol/l in a population sample of Finnish children. We studied 184 girls and 190 boys aged 6-8 years, analysed S-25(OH)D by chemiluminescence immunoassay and assessed diet quality using 4-d food records and other lifestyle factors by questionnaires. We analysed the determinants of S-25(OH)D using linear regression and risk factors for S-25(OH)D <50 nmol/l using logistic regression. Mean dietary intake of vitamin D was 5·9 (sd 2·1) µg/d. Altogether, 40·8 % of children used no vitamin D supplements. Of all children, 82·4 % did not meet the recommended total vitamin D intake of 10 µg/d. Milk fortified with vitamin D was the main dietary source of vitamin D, providing 48·7 % of daily intake. S-25(OH)D was <50 nmol/l in 19·5 % of children. Consumption of milk products was the main determinant of S-25(OH)D in all children (standardised regression coefficient β=0·262; P<0·001), girls (β=0·214; P=0·009) and boys (β=0·257; P=0·003) in multivariable models. Vitamin D intake from supplements (β=0·171; P=0·035) and age (β=-0·198; P=0·015) were associated with S-25(OH)D in girls. Children who drank ≥450 g/d of milk, spent ≥2·2 h/d in physical activity, had ≥13·1 h/d of daylight time or were examined in autumn had reduced risk for S-25(OH)D <50 nmol/l. Insufficient vitamin D intake was common among Finnish children, one-fifth of whom had S-25(OH)D <50 nmol/l. More attention should be paid to the sufficient intake of vitamin D from food and supplements, especially among children who do not use fortified milk products. PMID:26836317

  19. Clinical and microbiological outcome in septic patients with extremely low 25-hydroxyvitamin D levels at initiation of critical care.

    PubMed

    De Pascale, G; Vallecoccia, M S; Schiattarella, A; Di Gravio, V; Cutuli, S L; Bello, G; Montini, L; Pennisi, M A; Spanu, T; Zuppi, C; Quraishi, S A; Antonelli, M

    2016-05-01

    A relationship between vitamin D status and mortality in patients in intensive care units (ICU) has been documented. The present study aims to describe the clinical profile and sepsis-related outcome of critically ill septic patients with extremely low (<7 ng/mL) vitamin D levels at ICU admission. We conducted an observational study in the ICU of a teaching hospital including all patients admitted with severe sepsis/septic shock and undergoing 25-hydroxyvitamin D (25(OH)D) testing within the first 24 hours from admission. We studied 107 patients over 12 months. At ICU admission vitamin D deficiency (≤20 ng/mL) was observed in 93.5% of the patients: 57 (53.3%) showed levels <7 ng/mL. As primary outcome, sepsis-related mortality rate was higher in patients with vitamin D levels <7 ng/mL (50.9% versus 26%). Multivariate regression analysis showed that vitamin D concentration <7 ng/mL on ICU admission (p 0.01) and higher mean SAPS II (p <0.01) score were independent predictors of sepsis-related mortality. Patients with very low vitamin D levels suffered higher rate of microbiologically confirmed infections but a lower percentage of microbiological eradication with respect to patients whose values were >7 ng/mL (80.7% versus 58%, p 0.02; 35.3% versus 68%; p 0.03, respectively). Post hoc analysis showed that, in the extremely low vitamin D group, the 52 patients with pneumonia showed a longer duration of mechanical ventilation (9 days (3.75-12.5 days) versus 4 days (2-9 days), p 0.04) and the 66 with septic shock needed vasopressor support for a longer period of time (7 days (4-10 days) versus 4 days (2-7.25 days), p 0.02). Our results suggest that in critical septic patients extremely low vitamin D levels on admission may be a major determinant of clinical outcome. Benefits of vitamin D replacement therapy in this population should be elucidated. PMID:26721785

  20. Does serum 25-hydroxyvitamin D influence muscle development during puberty in girls? A 7-year longitudinal study.

    PubMed

    Wang, Ru; Alen, Markku; Yu, Zhusheng; Wiklund, Petri; Cheng, Shu Mei; Törmäkangas, Timo; Chen, Peijie; Cheng, Sulin

    2013-01-01

    Vitamin D is well known for its regulatory role in calcium and phosphate homeostasis, but its role in muscle mass and strength during growth remains inconclusive. We explored the association of serum 25-hydroxyvitamin D (25(OH)D) with muscle development in girls from 11 to 18-years old. Whole body lean tissue mass (LMWB), appendicular lean mass (aLM), muscle cross-sectional area at the lower leg (mCSA), maximal voluntary contraction of elbow flexors (MVC elbow) and knee extensors (MVC knee) were assessed in 217 girls aged 10-13 years (at baseline), 215 in 2-year and 226 in 7.5-year follow-up. Serum concentration of 25(OH)D and intact parathyroid hormone (PTH) were analyzed retrospectively and girls were categorized according to their 25(OH)D levels (consistently insufficient 25(OH)D GLL <50 nmol/l and consistently sufficient GHH >50 nmol/l from baseline to 7-year follow-up). We found that 25(OH)D level declined until menarche (p<0.05) while LMWB, aLM, mCSA, MVC elbow and MVC knee continued to increase (p<0.001 for all) post menarche. At pre-menarche, the GLL (n = 34) had higher LMWB and aLM than the GHH (n = 21, p<0.05), while post-menarche the GHH (n = 15) had a greater catch-up gain in LMWB (p = 0.004), aLM (p = 0.001) and mCSA (p = 0.027) compared to the GLL (n = 65) over the first 2-year period. At the age of 18, no differences in muscle mass/strength between the low (n = 151) and high (n = 77) levels of 25(OH)D groups were found. This finding was independent of vitamin D receptor genotype and other confounders. In conclusion, our results showed that levels of 25(OH)D have no significant negative influence on the development of muscle mass and strength during pubertal growth both with longitudinal and cross-sectional comparison. On the contrary, our results suggest that the temporary negative association between 25(OH)D and muscle mass arises as a consequence of fast growth prior to menarche, and this negative association is diminished through catch-up growth

  1. Fracture Risk in Relation to Serum 25-Hydroxyvitamin D and Physical Activity: Results from the EPIC-Norfolk Cohort Study

    PubMed Central

    Julian, Cristina; Lentjes, Marleen A. H.; Huybrechts, Inge; Wareham, Nick; Khaw, Kay-Tee

    2016-01-01

    Vitamin D deficiency and physical inactivity have been associated with bone loss and fractures, but their combined effect has scarcely been studied either in younger or older adults. Therefore, we aimed to assess the associations between physical activity, age and 25-hydroxyvitamin D (25(OH)D) status separately and in combination with the incidence of fracture risk in the EPIC-Norfolk cohort study. Baseline (1993–1998) self-reported physical activity and serum 25(OH)D concentrations at follow-up (1998–2000) were collected in 14,624 men and women (aged 42–82 y between 1998 and 2000). Fracture incidence was ascertained up to March 2015. Cox proportional hazard model was used to determine HRs of fractures by plasma 25(OH)D (<30, 30 to <50, 50 to <70, 70 to <90, >90 nmol/L), age (<65 y and >65 y) and physical activity (inactive and active) categories, by follow-up time per 20 nmol/L increase in serum 25(OH)D and to explore age-25(OH)D and physical activity-25(OH)D interactions. The age-, sex-, and month-adjusted HRs (95% CIs) for all fractures (1183 fractures) by increasing vitamin D category were not significantly different. With additional adjustment for body mass index, smoking status, alcohol intake, supplement use and history of fractures, the fracture risk was 29% lower in those participants with 50 to 70 nmol/L compared with those in the lowest quintile (<30 nmol/L). Physical inactivity based on a single baseline assessment was not associated with fracture risk. Vitamin D status appeared inversely related to fractures in middle aged adults. In older adults, the relationship between vitamin D status and fracture risk was observed to be J-shaped. Clinical and public health practice in vitamin D supplementation could partially explain these findings, although definitive conclusions are difficult due to potential changes in exposure status over the long follow up period. PMID:27749911

  2. The predictive factors of low serum 25-hydroxyvitamin D and vitamin D deficiency in patients with systemic lupus erythematosus.

    PubMed

    Sumethkul, Kittiwan; Boonyaratavej, Smonporn; Kitumnuaypong, Tasanee; Angthararuk, Sungchai; Cheewasat, Patcharin; Manadee, Naruimon; Sumethkul, Vasant

    2013-06-01

    Vitamin D is a steroid hormone with pleiotropic effects. The association between serum 25-hydroxyvitamin D level [25(OH) D] and lupus nephritis are not clearly known. We aim to determine serum 25(OH) D levels in patients with inactive SLE, active SLE without lupus nephritis (LN) and active SLE with LN and to identify clinical predictor of vitamin D deficiency. One hundred and eight SLE patients were included. Patients were classified as Group (Gr) 1, 2 and 3 if they had SLE disease activity index (SLEDAI) <3, ≥ 3 but no LN and ≥ 3 with LN. Important baseline characteristics were collected. 25(OH) D was measured by high performance liquid chromatography (HPLC). SLEDAI in Gr1, Gr2 and Gr3 was 0.7 (0.9), 5.6 (2.3) and 9.2 (5.2), respectively. 43.5 % had vitamin D insufficiency and 29.6 % had vitamin D deficiency. Mean 25(OH) D in each groups was 28.3 (8.0), 26.7 (9.5) and 19.9 (7.6) ng/ml (p < 0.001 comparing Gr1 and 3) (p = 0.003 comparing Gr2 and 3). Vitamin D deficiency was found in 11.1, 22.2 and 55.6 % of Gr1, 2 and 3. Linear regression analysis found that 25(OH) D was significantly correlated with serum albumin (r = 0.28, p = 0.004), inversely correlated with SLEDAI (r = -0.22, p = 0.03) and urinary protein creatinine index (UPCI) (r = -0.28, p = 0.005), but not with sun exposure score, body mass index and estimated GFR. Only UPCI was significantly inversely correlated with 25(OH) D (p = 0.02) from multiple linear regression. LN was a significant predictor of vitamin D deficiency from multivariate logistic regression (OR 5.97; p = 0.006). Vitamin D deficiency and insufficiency was found in 93 and 86 % of LN with proteinuria ≥ and <500 mg/day. We conclude that SLE patients with LN have significantly lower vitamin D level than inactive SLE and active SLE without LN. Hence, nephritis is a significant predictor of vitamin D deficiency in SLE patients.

  3. Serum 25-Hydroxyvitamin D, Transitions between Frailty States, and Mortality among Older Adults: The Invecchiare in Chianti Study

    PubMed Central

    Shardell, Michelle; D’Adamo, Christopher; Alley, Dawn E; Miller, Ram R; Hicks, Gregory E; Milaneschi, Yuri; Semba, Richard D; Cherubini, Antonio; Bandinelli, Stefania; Ferrucci, Luigi

    2011-01-01

    OBJECTIVES Frailty is a dynamic geriatric syndrome characterized by decreased reserve and increased vulnerability. Low serum 25-hydroxyvitamin D [25(OH)D] concentrations in older adults are associated with many physiological changes that portend frailty and its consequences. We aimed to assess whether serum 25(OH)D concentrations relate to transitions between the states of robustness, prefrailty, and frailty, and to mortality. DESIGN, SETTING, and PARTICIPANTS Adults aged≥65 years (N=1,155) enrolled in Invecchiare in Chianti (InCHIANTI), a prospective cohort study in Tuscany, Italy. MEASUREMENTS Serum 25(OH)D concentrations measured at baseline and frailty state (robust, prefrail, frail) assessed at baseline and at three and six years post enrollment. Vital status was also determined at three and six years post enrollment. RESULTS The median (interquartile range) 25(OH)D concentration was 16.0 (10.4—25.6) ng/mL (multiply by 2.496 to convert to nmol/L). Prefrail participants with 25(OH)D<20 ng/mL were 8.9% (95% Confidence Interval [CI], 2.5—15.2%) more likely to die, 3.0% (95%CI, −5.6—14.6%) more likely to become frail, and 7.7% (95%CI, −3.5—18.7%) less likely to become robust than prefrail participants with 25(OH)D≥20 ng/mL. Among prefrail participants, each 5 ng/mL decrement of continuous 25(OH)D was associated with 1.46 times higher odds of dying (95%CI, 1.18—2.07) and 1.13 higher odds of incident frailty (95%CI, 0.90—1.39) versus recovery of robustness. Transitions from robustness or frailty were not associated with 25(OH)D. CONCLUSION Results provide evidence that prefrailty is an “at risk” state from which older adults with high 25(OH)D are more likely to recover than to decline. However, high 25(OH)D was not associated with recovery from frailty. Thus, 25(OH)D should be investigated as a potential therapy to treat prefrailty and prevent further decline. PMID:22283177

  4. 25-Hydroxyvitamin D insufficiency discriminates cardiovascular risk factors accumulation in peri-pubertal boys undergoing overweight screening.

    PubMed

    Di Nisio, Andrea; De Toni, Luca; D'Addato, Elvio; Pizzo, Maria R; Sabatino, Pasquale; Foresta, Carlo

    2016-08-01

    The aim of this study was to evaluate the possible association between cardiometabolic risk factors accumulation and vitamin D status in a cohort of Italian normal weight and overweight male children. 108 boys enrolled in an andrological health prevention project underwent physical examination, anthropometric measurements, and fasting blood sampling. Serum blood glucose, HDL-cholesterol, triglycerides, parathyroid hormone, and 25-hydroxyvitamin D (25(OH)D) were measured. Cardiovascular risk factors were defined according to the National Cholesterol Education Program Adult Treatment Panel III modified for age. Lean and overweight subjects differed in terms of waist circumference (P < 0.001), HDL-cholesterol (P = 0.001), triglycerides (P = 0.001), systolic blood pressure (P < 0.001) and diastolic blood pressure (P = 0.002). Both groups had similar mean 25(OH)D levels (P = 0.160) and were below the sufficiency threshold: indeed only 24 % of normal weight had 25(OH)D ≥30 ng/ml, and even less in the overweight/obese group (8 %, P = 0.03 vs. normal weight). A significant accumulation of risk factors in course of 25(OH)D insufficiency was detected in both the whole cohort and in the normal weight group (P = 0.003 and P = 0.04, respectively) with odd ratios of 1.31 (1.16-1.49 95%CI) and 1.41 (1.18-1.69 95%CI), respectively. In course of vitamin D deficiency, the odd ratios were 2.24 (1.34-3.77 95%CI, P = 0.003) in the whole cohort and 2.40 (1.27-4.82 95%CI, P = 0.03) in lean subjects. We reported a considerable occurrence of cardiovascular risk factors in course of hypovitaminosis D in overweight/obese boys and even in lean subjects, which normally would not have been further evaluated by considering the sole BMI-related parameters. In this regard, 25(OH)D levels appear as a potential discriminating parameter able to identify male children at higher health risk.

  5. Effects of Fok-I polymorphism in vitamin D receptor gene on serum 25-hydroxyvitamin D, bone-specific alkaline phosphatase and calcaneal quantitative ultrasound parameters in young adults.

    PubMed

    Tanabe, Rieko; Kawamura, Yuka; Tsugawa, Naoko; Haraikawa, Mayu; Sogabe, Natsuko; Okano, Toshio; Hosoi, Takayuki; Goseki-Sone, Masae

    2015-01-01

    Several genes have been implicated as genetic determinants of osteoporosis. Vitamin D receptor (VDR) is an intracellular hormone receptor that specifically binds to the biologically active form of vitamin D, 1-alpha, 25- dihydroxyvitamin D3 [1, 25(OH)2D], and mediates its effects. One of the most frequently studied single nucleotide polymorphisms is the restriction fragment length polymorphism (RFLP) Fok-I (rs2228570). The presence of a Fok-I site, designated f, allows protein translation to initiate from the first ATG. An allele lacking the site (ATG>ACG: designated F), initiates from a second ATG site. In the present study, we explored the effect of the VDR Fok-I genotype on associations among serum bone-specific alkaline phosphatase (ALP), 25- hydroxyvitamin D3 [25(OH)D], 1, 25(OH)2D, and the dietary nutrient intake in healthy young Japanese subjects (n=193). Dietary nutrient intakes were calculated based on 3-day food records before the day of blood examinations. Quantitative ultrasound (QUS) parameters at the right calcaneus (heel bone) were measured. The allele frequencies were 0.622 for the F allele and 0.378 for the f allele in all subjects. Grouped by the VDR genotype, a significant positive correlation between the levels of serum bone-specific ALP and 25(OH)D was observed in the FF-type (p=0.005), but not in the ff-type. In addition, there was a significant positive correlation between the level of serum 25(OH)D and osteo-sono assessment index (OSI) in the FF-type (p=0.008), but not in the ff-type. These results suggest that the level of circulating 25(OH)D is an important factor when assessing the VDR Fok-I polymorphism to prevent osteoporosis. PMID:26078251

  6. Effects of Fok-I polymorphism in vitamin D receptor gene on serum 25-hydroxyvitamin D, bone-specific alkaline phosphatase and calcaneal quantitative ultrasound parameters in young adults.

    PubMed

    Tanabe, Rieko; Kawamura, Yuka; Tsugawa, Naoko; Haraikawa, Mayu; Sogabe, Natsuko; Okano, Toshio; Hosoi, Takayuki; Goseki-Sone, Masae

    2015-01-01

    Several genes have been implicated as genetic determinants of osteoporosis. Vitamin D receptor (VDR) is an intracellular hormone receptor that specifically binds to the biologically active form of vitamin D, 1-alpha, 25- dihydroxyvitamin D3 [1, 25(OH)2D], and mediates its effects. One of the most frequently studied single nucleotide polymorphisms is the restriction fragment length polymorphism (RFLP) Fok-I (rs2228570). The presence of a Fok-I site, designated f, allows protein translation to initiate from the first ATG. An allele lacking the site (ATG>ACG: designated F), initiates from a second ATG site. In the present study, we explored the effect of the VDR Fok-I genotype on associations among serum bone-specific alkaline phosphatase (ALP), 25- hydroxyvitamin D3 [25(OH)D], 1, 25(OH)2D, and the dietary nutrient intake in healthy young Japanese subjects (n=193). Dietary nutrient intakes were calculated based on 3-day food records before the day of blood examinations. Quantitative ultrasound (QUS) parameters at the right calcaneus (heel bone) were measured. The allele frequencies were 0.622 for the F allele and 0.378 for the f allele in all subjects. Grouped by the VDR genotype, a significant positive correlation between the levels of serum bone-specific ALP and 25(OH)D was observed in the FF-type (p=0.005), but not in the ff-type. In addition, there was a significant positive correlation between the level of serum 25(OH)D and osteo-sono assessment index (OSI) in the FF-type (p=0.008), but not in the ff-type. These results suggest that the level of circulating 25(OH)D is an important factor when assessing the VDR Fok-I polymorphism to prevent osteoporosis.

  7. High frequency of deficient consumption and low blood levels of 25-hydroxyvitamin D in HIV-1-infected adults from São Paulo city, Brazil.

    PubMed

    Sales, Stephanie Hael; Matta, Sandra Maria; da Matta, Sandra; da Silva, Daniela Cardeal; Assone, Tatiane Assone; Fonseca, Luiz Augusto M; Duarte, Alberto J S; Casseb, Jorge

    2015-01-01

    Micronutrient deficiency is common in patients with HIV/AIDS, usually caused by mal-absorption and/or drug interactions. 25-hydroxyvitamin D is of fundamental importance for the homeostasis of musculoskeletal health. The current study aimed to evaluate the nutritional status of HIV-infected subjects in order to make their nutritional diagnoses, including their vitamin D blood levels, and to estimate their consumption of vitamin D. The study included 98 HIV-1-infected subjects, followed at University of São Paulo Medical School - HC-FMUSP. We performed a nutritional evaluation, along with the determination of patients' serum 25-hydroxyvitamin D and calcium concentration, biochemical analyses, and an anthropometric assessment. In the medical interview a 24-hour food recall was used (R24) to estimate daily calorie intake, macronutrients, calcium, and vitamin D. A high level of vitamin D deficiency was observed in our patients: 83.4% of them had levels below 30 ng/ml; they also presented an increased risk of cardiovascular disease, along with a high consumption of dietary fat. Factors related to the virus itself and to the use of antiretroviral drugs may have contributed for the low vitamin D levels seen in our HIV-1-infected patients.

  8. Vitamin D in a Northern Canadian First Nation Population: Dietary Intake, Serum Concentrations and Functional Gene Polymorphisms

    PubMed Central

    Larcombe, Linda; Mookherjee, Neeloffer; Slater, Joyce; Slivinski, Caroline; Singer, Matthew; Whaley, Chris; Denechezhe, Lizette; Matyas, Sara; Turner-Brannen, Emily; Nickerson, Peter; Orr, Pamela

    2012-01-01

    The wide spectrum of vitamin D activity has focused attention on its potential role in the elevated burden of disease in a northern Canadian First Nations (Dené) cohort. Vitamin D insufficiency, and gene polymorphisms in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) have been implicated in susceptibility to infectious and chronic diseases. The objectives of this study were to determine the contribution of vitamin D from food, and measure the serum concentrations of 25-hydroxyvitamin D3 (25-OHD3) and VDBP in Dené participants. Single nucleotide polymorphisms (SNPs) associated with the dysregulation of the innate immune response were typed and counted. Potential correlations between the SNPs and serum concentrations of 25-OHD3 and VDBP were evaluated. Venous blood was collected in summer and winter over a one-year period and analyzed for 25-OHD3 and VDBP concentrations (N = 46). A questionnaire was administered to determine the amount of dietary vitamin D consumed. Sixty-one percent and 30% of the participants had 25-OHD3 serum concentrations <75 nmol/L in the winter and summer respectively. Mean vitamin D binding protein concentrations were within the normal range in the winter but below normal in the summer. VDBP and VDR gene polymorphisms affect the bioavailability and regulation of 25-OHD3. The Dené had a high frequency of the VDBP D432E-G allele (71%) and the Gc1 genotype (90%), associated with high concentrations of VDBP and a high binding affinity to 25-OHD3. The Dené had a high frequency of VDR Fok1-f allele (82%), which has been associated with a down-regulated Th1 immune response. VDBP and VDR polymorphisms, and low winter 25-OHD3 serum concentrations may be risk factors for infectious diseases and chronic conditions related to the dysregulation of the vitamin D pathway. PMID:23185470

  9. Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women.

    PubMed

    Pfeifer, M; Begerow, B; Minne, H W; Nachtigall, D; Hansen, C

    2001-04-01

    Calcium supplementation is effective in reducing blood pressure in various states of hypertension, including pregnancy-induced hypertension and preeclampsia. In addition, calcitropic hormones are associated with blood pressure. The hypothesis is that short-term therapy with calcium and vitamin D(3) may improve blood pressure as well as secondary hyperparathyroidism more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D(3) (cholecalciferol) and calcium on blood pressure and biochemical measures of bone metabolism were studied. The sample consisted of 148 women (mean +/- SD age, 74 +/- 1 yr) with a 25-hydroxycholecalciferol (25OHD(3)) level below 50 nmol/L. They received either 1200 mg calcium plus 800 IU vitamin D(3) or 1200 mg calcium/day. We measured intact PTH, 25OHD(3), 1,25-dihydroxyvitamin D(3), blood pressure, and heart rate before and after treatment. Compared with calcium, supplementation with vitamin D(3) and calcium resulted in an increase in serum 25OHD(3) of 72% (P < 0.01), a decrease in serum PTH of 17% (P = 0.04), a decrease in systolic blood pressure (SBP) of 9.3% (P = 0.02), and a decrease in heart rate of 5.4% (P = 0.02). Sixty subjects (81%) in the vitamin D(3) and calcium group compared with 35 (47%) subjects in the calcium group showed a decrease in SBP of 5 mm Hg or more (P = 0.04). No statistically significant difference was observed in the diastolic blood pressures of the calcium-treated and calcium- plus vitamin D(3)-treated groups (P = 0.10). Pearson coefficients of correlation between the change in PTH and the change in SBP were 0.49 (P < 0.01) for the vitamin D(3) plus calcium group and 0.23 (P < 0.01) for the calcium group. A short-term supplementation with vitamin D(3) and calcium is more effective in reducing SBP than calcium alone. Inadequate vitamin D(3) and calcium intake could play a contributory role in the pathogenesis and progression of hypertension and cardiovascular disease in

  10. A simultaneous quantitative method for vitamins A, D and E in human serum using liquid chromatography-tandem mass spectrometry.

    PubMed

    Albahrani, Ali A; Rotarou, Victor; Roche, Peter J; Greaves, Ronda F

    2016-05-01

    Non-classical roles of fat-soluble vitamins (FSVs) in many pathologies including cancer have been identified. There is also evidence of hormonal interactions between two of these vitamins, A and D. As a result of this enhanced clinical association with disease, translational clinical research and laboratory requests for FSV measurement has significantly increased. However there are still gaps in the analytical methods available for the measurement of these vitamins. This study aimed to develop a method for simultaneous quantification of 25-hydroxyvitamin-D2 (25-OHD2), 25-hydroxyvitamin-D3 (25-OHD3) and its 3-epimer (epi-25-OHD3), retinol and α-tocopherol in human serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The procedure was developed and validated across two LC-MS/MS platforms, using commercial calibrators referenced to certified reference materials, controls, and deuterated internal standards. The samples were prepared by liquid-liquid extraction prior to injection and LC separation (using a Pursuit-PFP column) on two Agilent MS/MS systems (6410 and 6490) in electrospray ionisation positive mode with multiple reaction monitoring. Identification and quantification of 25-OHD3 from its 3-epimer as well as 25-OHD2, retinol and α-tocopherol were achieved. The dynamic ranges were 4-160 nmol/L for 25-OHD2 and epi-25-OHD3, 4-200 nmol/L for 25-OHD3, 0.1-4.0μmol/L for retinol and 4-70μmol/L for α-tocopherol with correlation (r(2)) of 0.997-0.998. Based on participation in an external quality assurance program, the overall performance of the simultaneous methods were: imprecision (CV%) and inaccuracy (average bias) 3.0% and 3.2 nmol/L, respectively, for 25-OHD3; 5.0% and 0.04μmol/L, respectively, for retinol; and 4.7% and 0.2μmol/L, respectively, for α-tocopherol. In summary, two simple LC-MS/MS methods were successfully developed and validated for the simultaneous quantification of the three vitamin D metabolites (25-OHD2, 25-OHD3 and 3

  11. Positive correlation between circulating cathelicidin antimicrobial peptide (hCAP18/LL-37) and 25-hydroxyvitamin D levels in healthy adults

    PubMed Central

    2012-01-01

    Background Transcription of the cathelicidin antimicrobial peptide (CAMP) gene is induced by binding of the bioactive form of vitamin D, 1,25-dihydroxyvitamin D, to the vitamin D receptor. Significant levels of the protein hCAP18/LL-37 are found in the blood and may protect against infection and/or sepsis. We hypothesized that serum vitamin D levels may modulate the circulating levels of hCAP18. Only three studies have shown a positive correlation between circulating 25-hydroxyvitamin D and hCAP18 levels. Here we provide additional evidence for such a correlation in healthy, middle-aged adults. Findings Serum levels of 25-hydroxyvitamin D [25(OH)D] and plasma levels of hCAP18 were determined in 19 healthy middle-aged (mean of 50.1 years) adult men and women. Plasma hCAP18 concentrations correlated with serum 25(OH)D concentrations in subjects with 25(OH)D levels ≤ 32 ng/ml (r = 0.81, p < 0.005) but not in subjects with concentrations > 32 ng/ml (r = 0.19, p = 0.63). Conclusions We conclude that plasma hCAP18 levels correlate with serum 25(OH)D levels in subjects with concentrations of 25(OH)D ≤ 32 ng/ml as opposed to those with concentrations > 32 ng/ml and that vitamin D status may regulate systemic levels of hCAP18/LL-37. PMID:23095332

  12. Very Low Levels of 25-Hydroxyvitamin D Are Not Associated With Immunologic Changes or Clinical Outcome in South African Patients With HIV-Associated Cryptococcal Meningitis

    PubMed Central

    Jarvis, Joseph N.; Bicanic, Tihana; Loyse, Angela; Meintjes, Graeme; Hogan, Louise; Roberts, Chrissy H.; Shoham, Shmuel; Perfect, John R.; Govender, Nelesh P.; Harrison, Thomas S.

    2014-01-01

    Background. Vitamin D deficiency is associated with impaired immune responses and increased susceptibility to a number of intracellular pathogens in individuals infected with human immunodeficiency virus (HIV). It is not known whether such an association exists with Cryptococcus neoformans. Methods. Levels of 25-hydroxyvitamin D (25[OH]D) were measured in 150 patients with cryptococcal meningitis (CM) and 150 HIV-infected controls in Cape Town, South Africa, and associations between vitamin D deficiency and CM were examined. The 25-hydroxyvitamin D levels and cryptococcal notifications were analyzed for evidence of reciprocal seasonality. Associations between 25(OH)D levels and disease severity, immune responses, and microbiological clearance were investigated in the patients with CM. Results. Vitamin D deficiency (plasma 25[OH]D ≤50 nmol/L) was present in 74% of patients. Vitamin D deficiency was not associated with CM (adjusted odds ratio, 0.93 [95% confidence interval, .6–1.6]; P = .796). Levels of 25(OH)D showed marked seasonality, but no reciprocal seasonality was seen in CM notifications. No significant associations were found between 25(OH)D levels and fungal burden or levels of tumor necrosis factor α, interferon γ, interleukin 6, soluble CD14, or neopterin in cerebrospinal fluid. Rates of fungal clearance did not vary according to vitamin D status. Conclusions. Vitamin D deficiency does not predispose to the development of CM, or lead to impaired immune responses or microbiological clearance in HIV-infected patients with CM. PMID:24825871

  13. Antenatal endotoxin disrupts lung vitamin D receptor and 25-hydroxyvitamin D 1α-hydroxylase expression in the developing rat.

    PubMed

    Mandell, Erica; Seedorf, Gregory J; Ryan, Sharon; Gien, Jason; Cramer, Scott D; Abman, Steven H

    2015-11-01

    Vitamin D [vit D; 1,25-(OH)2D] treatment improves survival and lung alveolar and vascular growth in an experimental model of bronchopulmonary dysplasia (BPD) after antenatal exposure to endotoxin (ETX). However, little is known about lung-specific 1,25-(OH)2D3 regulation during development, especially regarding maturational changes in lung-specific expression of the vitamin D receptor (VDR), 1α-hydroxylase (1α-OHase), and CYP24A1 during late gestation and the effects of antenatal ETX exposure on 1,25-(OH)2D3 metabolism in the lung. We hypothesized that vit D regulatory proteins undergo maturation regulation in the late fetal and early neonatal lung and that prenatal exposure to ETX impairs lung growth partly through abnormal endogenous vit D metabolism. Normal fetal rat lungs were harvested between embryonic day 15 and postnatal day 14. Lung homogenates were assayed for VDR, 1α-OHase, and CYP24A1 protein contents by Western blot analysis. Fetal rats were injected on embryonic day 20 with intra-amniotic ETX, ETX + 1,25-(OH)2D3, or saline and delivered 2 days later. Pulmonary artery endothelial cells (PAECs) from fetal sheep were assessed for VDR, 1α-OHase, and CYP24A1 expression after treatment with 25-(OH)D3, 1,25-(OH)2D3, ETX, ETX + 25-(OH)D3, or ETX + 1,25-(OH)2D3. We found that lung VDR, 1α-OHase, and CYP2741 protein expression dramatically increase immediately before birth (P < 0.01 vs. early fetal values). Antenatal ETX increases CYP24A1 expression (P < 0.05) and decreases VDR and 1α-OHase expression at birth (P < 0.001), but these changes are prevented with concurrent vit D treatment (P < 0.001). ETX-induced reduction of fetal PAEC growth and tube formation and lung 1α-OHase expression are prevented by vit D treatment (P < 0.001). We conclude that lung VDR, 1α-OHase, and CYP24A1 protein content markedly increase before birth and that antenatal ETX disrupts lung vit D metabolism through downregulation of VDR and increased vit D catabolic enzyme

  14. A systematic review of the influence of skin pigmentation on changes in the concentrations of vitamin D and 25-hydroxyvitamin D in plasma/serum following experimental UV irradiation.

    PubMed

    Xiang, Fan; Lucas, Robyn; de Gruijl, Frank; Norval, Mary

    2015-12-01

    Defining whether skin pigmentation influences vitamin D photosynthesis is important for delivering accurate public health messages. Current evidence is contradictory. We undertook a systematic review of the published literature to examine the association between skin pigmentation and change in blood concentrations of vitamin D and 25-hydroxyvitamin D following experimental UV irradiation. Twelve studies fulfilled the inclusion criteria: human study in vivo with non-diseased participants; controlled artificial UV radiation; vitamin D or 25-hydroxyvitamin D measured in serum or plasma; full text in English. In seven studies, vitamin D photosynthesis was reduced in dark-skinned compared with fairer-skinned individuals. In the remaining five studies, only one of which was published after 1990, there was no difference in vitamin D photosynthesis according to skin type. The disparities in these results may be due to small sample sizes and variations in study methodology, including the source, dose and frequency of UV irradiation, phototype classification, and analysis of vitamin D and 25-hydroxyvitamin D. Of these, the spectrum emitted by the UV lamps may be significant. No study considered potential modifying factors, such as relevant genetic polymorphisms. On balance, we conclude that pigmented skin has less effective photoproduction of vitamin D and 25-hydroxyvitamin D. The quantity of sun exposure needed for dark-skinned, compared with light-skinned, people to achieve vitamin D sufficiency remains uncertain.

  15. Two-dimensional liquid chromatography coupled to tandem mass spectrometry for vitamin D metabolite profiling including the C3-epimer-25-monohydroxyvitamin D3.

    PubMed

    Mena-Bravo, A; Priego-Capote, F; Luque de Castro, M D

    2016-06-17

    A method based on automated on-line solid phase extraction coupled to two-dimensional liquid chromatography with tandem mass spectrometry detection (SPE-2DLC-MS/MS) is here reported for vitamin D metabolite profiling in human serum with absolute quantitation. Two-dimensional LC was configured with two complementary analytical columns, pentafluorophenyl (PFP) and C18 phases, for determination of 25 hydroxyvitamin D3 epimers and the resting bioactive metabolites of vitamin D (D3 and D2)-25-hydroxyvitamin D2, 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D2 and 24,25-dihydroxyvitamin D3. Quantitative determination was supported on the use of a stable isotopic labelled internal standard for each analyte and the resulting method was validated by analysis of a standard reference material certified by the National Institute of Standards & Technology (NIST-972a) and 5 samples provided by the vitamin D External Quality Assurance Scheme (DEQAS). The limits of detection were between 9 and 90pg/mL for the eight analytes, and precision, expressed as relative standard deviation, was lower than 11.6%. Two-dimensional LC has shown to be the key to discriminate between 25 hydroxyvitamin D3 epimers in a quantitative analysis also involving dihydroxyvitamin D metabolites.

  16. Metabolism and pharmacokinetics of 24,25-dihydroxyvitamin D3 in the vitamin D3-replete rat

    SciTech Connect

    Jarnagin, K.; Zeng, S.Y.; Phelps, M.; DeLuca, H.F.

    1985-11-05

    The time course of in vivo metabolism of 24,25-dihydroxyvitamin D3 in rats has been examined. Several tissues were surveyed in an effort to discover new metabolites of 24,25-dihydroxyvitamin D3 and to estimate the concentrations of previously identified metabolites. Rapidly growing male rats were dosed with 24,25-dihydroxyvitamin D3 orally until plasma concentrations of 24,25-dihydroxyvitamin D3 were at steady state. 24,25-Dihydroxyvitamin (3-TH)D3 was then administered. At 10 min and 1, 6, 15, 24, 96, and 192 h after dosing, the animals were killed, and plasma, liver, intestine, and bones were analyzed with a newly developed gradient straight-phase high performance liquid chromatography system. The high performance liquid chromatography system is capable of base-line resolution of most of the major vitamin D metabolites. 24,25-Dihydroxyvitamin D3 clearance from plasma, liver, and kidney but not intestine followed a two-compartment model. 24,25-Dihydroxyvitamin D3 disappeared from plasma with a half-life of 0.55 h (fast phase) and 73.8 h (slow phase). Only two lipid-soluble metabolites of 24,25-dihydroxyvitamin D3 were detected: 24-oxo-25-hydroxyvitamin D3 and 1,24,25-trihydroxyvitamin D3. These compounds circulate at very low concentrations in the plasma (50 pg/ml of plasma).

  17. The role of 25-hydroxyvitamin D deficiency in promoting insulin resistance and inflammation in patients with Chronic Kidney Disease: a randomised controlled trial

    PubMed Central

    2009-01-01

    Background Approximately 50% of patients with stage 3 Chronic Kidney Disease are 25-hydroxyvitamin D insufficient, and this prevalence increases with falling glomerular filtration rate. Vitamin D is now recognised as having pleiotropic roles beyond bone and mineral homeostasis, with the vitamin D receptor and metabolising machinery identified in multiple tissues. Worryingly, recent observational data has highlighted an association between hypovitaminosis D and increased cardiovascular mortality, possibly mediated via vitamin D effects on insulin resistance and inflammation. The main hypothesis of this study is that oral Vitamin D supplementation will ameliorate insulin resistance in patients with Chronic Kidney Disease stage 3 when compared to placebo. Secondary hypotheses will test whether this is associated with decreased inflammation and bone/adipocyte-endocrine dysregulation. Methods/Design This study is a single-centre, double-blinded, randomised, placebo-controlled trial. Inclusion criteria include; estimated glomerular filtration rate 30-59 ml/min/1.73 m2; aged ≥18 on entry to study; and serum 25-hydroxyvitamin D levels <75 nmol/L. Patients will be randomised 1:1 to receive either oral cholecalciferol 2000IU/day or placebo for 6 months. The primary outcome will be an improvement in insulin sensitivity, measured by hyperinsulinaemic euglycaemic clamp. Secondary outcome measures will include serum parathyroid hormone, cytokines (Interleukin-1β, Interleukin-6, Tumour Necrosis Factor alpha), adiponectin (total and High Molecular Weight), osteocalcin (carboxylated and under-carboxylated), peripheral blood mononuclear cell Nuclear Factor Kappa-B p65 binding activity, brachial artery reactivity, aortic pulse wave velocity and waveform analysis, and indirect calorimetry. All outcome measures will be performed at baseline and end of study. Discussion To date, no randomised controlled trial has been performed in pre-dialysis CKD patients to study the correlation

  18. Disordered regulation of renal 25-hydroxyvitamin D-1alpha-hydroxylase gene expression by phosphorus in X-linked hypophosphatemic (hyp) mice.

    PubMed

    Azam, Nasreen; Zhang, Martin Y H; Wang, Xuemei; Tenenhouse, Harriet S; Portale, Anthony A

    2003-08-01

    X-linked hypophosphatemic (Hyp) mice exhibit hypophosphatemia, impaired renal phosphate reabsorption, defective skeletal mineralization, and disordered regulation of vitamin D metabolism: In Hyp mice, restriction of dietary phosphorus induces a decrease in serum concentration of 1,25-dihydroxyvitamin D and renal activity of 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase), and induces an increase in renal activity of 25-hydroxyvitamin D-24-hydroxylase (24-hydroxylase). In contrast, in wild-type mice, phosphorus restriction stimulates renal 1alpha-hydroxylase gene expression and suppresses that of 24-hydroxylase. To determine the molecular basis for the disordered regulation of vitamin D metabolism in Hyp mice, we determined renal mitochondrial 1alpha-hydroxylase activity and the renal abundance of p450c1alpha and p450c24 mRNA in wild-type and Hyp mice fed either control, low-, or high-phosphorus diets for 5 d. In wild-type mice, phosphorus restriction increased 1alpha-hydroxylase activity and p450c1alpha mRNA expression by 6-fold and 3-fold, respectively, whereas in the Hyp strain the same diet induced changes of similar magnitude but opposite in direction. Phosphorus supplementation was without effect in wild-type mice, whereas in Hyp mice the same diet induced 3-fold and 2-fold increases, respectively, in enzyme activity and p450c1alpha mRNA abundance. In wild-type mice, both renal 1alpha-hydroxylase activity and p450c1alpha mRNA abundance varied inversely and significantly with serum phosphorus concentrations, whereas in Hyp mice the relationship between both renal parameters and serum phosphorus concentration was direct. In Hyp mice, phosphorus restriction induced a significant increase in renal p450c24 mRNA abundance, in contrast to the lack of effect observed in wild-type mice. The present findings demonstrate that regulation of both the p450c1alpha and p45024 genes by phosphorus is disordered in Hyp mice at the level of renal 1alpha

  19. Association of Arsenic and Metals with Concentrations of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D among Adolescents in Torreón, Mexico

    PubMed Central

    Zamoiski, Rachel D.; Guallar, Eliseo; García-Vargas, Gonzalo G.; Rothenberg, Stephen J.; Resnick, Carol; Andrade, Marisela Rubio; Steuerwald, Amy J.; Parsons, Patrick J.; Weaver, Virginia M.; Navas-Acien, Ana

    2014-01-01

    Background: Limited data suggest that lead (Pb), cadmium (Cd), and uranium (U) may disrupt vitamin D metabolism and inhibit production of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active vitamin D metabolite, from 25-hydroxyvitamin D [25(OH)D] in the kidney. Objectives: We evaluated the association between blood lead (BPb) and urine arsenic (As), Cd, molybdenum (Mo), thallium (Tl), and U with markers of vitamin D metabolism [25(OH)D and 1,25(OH)2D]. Methods: We conducted a cross-sectional study of 512 adolescents in Torreón, a town in Mexico with a Pb smelter near residential areas. BPb was measured using atomic absorption spectrometry. Urine As, Cd, Mo, Tl, and U were measured using inductively coupled plasma mass spectrometry. Serum 25(OH)D and 1,25(OH)2D were measured using a chemiluminescent immunoassay and a radioimmunoassay, respectively. Multivariable linear models with vitamin D markers as the outcome were used to estimate associations of BPb and creatinine-corrected urine As and metal concentrations with serum vitamin D concentrations, controlling for age, sex, adiposity, smoking, socioeconomic status, and time outdoors. Results: Serum 25(OH)D was positively associated with urine Mo and Tl [1.5 (95% CI: 0.4, 2.6) and 1.2 (95% CI: 0.3, 2.1) ng/mL higher with a doubling of exposure, respectively]. Serum 1,25(OH)2D was positively associated with urine As and U [3.4 (95% CI: 0.9, 5.9) and 2.2 (95% CI: 0.7, 3.7) pg/mL higher, respectively], with little change in associations after additional adjustment for serum 25(OH)D. Pb and Cd were not associated with 25(OH)D or 1,25(OH)2D concentrations. Conclusions: Overall, our findings did not support a negative effect of As or metal exposures on serum 1,25(OH)2D concentrations. Additional research is needed to confirm positive associations between serum 1,25(OH)2D and urine U and As concentrations and to clarify potential underlying mechanisms. Citation: Zamoiski RD, Guallar E, García-Vargas GG, Rothenberg SJ

  20. Relationship between homeostasis model assessment of insulin resistance and beta cell function and serum 25-hydroxyvitamin D in non-diabetic Korean adults

    PubMed Central

    Yoon, Hyun; Jeon, Dae Jung; Park, Chang Eun; You, Hye Sook; Moon, Ae Eun

    2016-01-01

    The purpose of this study is to look at these relationships in non-diabetic Korean adults. This study was based on data from the KNHANES V-1, which is representative of the population of Korea. A total of 5,492 participants (≥20 years in age) without type 1 or type 2 diabetes, assessed for serum 25-hydroxyvitamin D [25(OH)D], fasting blood glucose and insulin, as well as anthropometric variables, were included in the analyses. The key study results were as follows: First, vitamin D status [vitamin D deficient, 25(OH)D <25 nM; vitamin D insufficient, 25(OH)D ≥25, <50 nM; vitamin D sufficient, 25(OH)D ≥50 nM] was inversely associated with homeostasis model assessment of insulin resistance (HOMA-IR) and beta cell function (HOMA-B) in model 2 (adjusted for age and gender) and 3 (further adjusted for smoking, alcohol drinking, regular exercise, systolic and diastolic blood pressure, waist circumference, and body mass index). Second, in model 4, when further adjusted for total cholesterol, triglycerides, and HDL-C, vitamin D status was inversely associated with HOMA-B. However, association of vitamin D status and HOMA-IR was no longer significant. In conclusion, vitamin D was inversely associated with beta cell function in non-diabetic Korean adults but was not associated with insulin resistance.

  1. A Randomised, Cross-Over Study to Estimate the Influence of Food on the 25-Hydroxyvitamin D₃ Serum Level after Vitamin D₃ Supplementation.

    PubMed

    Cavalier, Etienne; Jandrain, Bernard; Coffiner, Monte; Da Silva, Stéphanie; De Niet, Sophie; Vanderbist, Francis; Souberbielle, Jean-Claude

    2016-01-01

    Vitamin D₃ is known to be liposoluble and its release could be a factor limiting the rate of absorption. It was presumed that the presence of fat could favor absorption of vitamin D₃. However, as bioavailability is related not only to the active molecules but also to the formulations and excipients used, the optimization of the pharmaceutical form of vitamin D₃ is also important. The objective of this study was to evaluate if there is a food effect on absorption when a high dose of vitamin D₃ is completely solubilized in an oily solution. In the present cross-over study, 88 subjects were randomized and received a single dose of 50,000 IU of vitamin D₃ in fasting state or with a standardized high-fat breakfast. Assessment of serum concentrations of 25 hydroxyvitamin D₃ (25(OH)D₃) was performed three, five, seven, 14, 30 and 60 days after supplementation. In fed and fast conditions, the 25(OH)D₃ serum concentrations were significantly higher than the baseline value three days after administration and remained significantly higher during the first month. No significant difference between fasting vs. fed conditions was observed. It is therefore concluded that the vitamin D₃ absorption from an oily solution was not influenced by the presence or absence of a meal. PMID:27213447

  2. The contributions of solar ultraviolet radiation exposure and other determinants to serum 25-hydroxyvitamin D concentrations in Australian adults: the AusD Study.

    PubMed

    Kimlin, Michael G; Lucas, Robyn M; Harrison, Simone L; van der Mei, Ingrid; Armstrong, Bruce K; Whiteman, David C; Kricker, Anne; Nowak, Madeleine; Brodie, Alison M; Sun, Jiandong

    2014-04-01

    The Quantitative Assessment of Solar UV [ultraviolet] Exposure for Vitamin D Synthesis in Australian Adults (AusD) Study aimed to better define the relationship between sun exposure and serum 25-hydroxyvitamin D (25(OH)D) concentration. Cross-sectional data were collected between May 2009 and December 2010 from 1,002 participants aged 18-75 years in 4 Australian sites spanning 24° of latitude. Participants completed the following: 1) questionnaires on sun exposure, dietary vitamin D intake, and vitamin D supplementation; 2) 10 days of personal ultraviolet radiation dosimetry; 3) a sun exposure and physical activity diary; and 4) clinical measurements and blood collection for 25(OH)D determination. Our multiple regression model described 40% of the variance in 25(OH)D concentration; modifiable behavioral factors contributed 52% of the explained variance, and environmental and demographic or constitutional variables contributed 38% and 10%, respectively. The amount of skin exposed was the single strongest contributor to the explained variance (27%), followed by location (20%), season (17%), personal ultraviolet radiation exposure (8%), vitamin D supplementation (7%), body mass index (weight (kg)/height (m)(2)) (4%), and physical activity (4%). Modifiable behavioral factors strongly influence serum 25(OH)D concentrations in Australian adults. In addition, latitude was a strong determinant of the relative contribution of different behavioral factors.

  3. The AusD Study: a population-based study of the determinants of serum 25-hydroxyvitamin D concentration across a broad latitude range.

    PubMed

    Brodie, A M; Lucas, R M; Harrison, S L; van der Mei, I A F; Armstrong, B; Kricker, A; Mason, R S; McMichael, A J; Nowak, M; Whiteman, D C; Kimlin, M G

    2013-05-01

    Observational studies suggest that people with a high serum 25-hydroxyvitamin D (25(OH)D) concentration may have reduced risk of chronic diseases such as osteoporosis, multiple sclerosis, type 1 diabetes, cardiovascular disease, and some cancers. The AusD Study (A Quantitative Assessment of Solar UV Exposure for Vitamin D Synthesis in Australian Adults) was conducted to clarify the relationships between ultraviolet (UV) radiation exposure, dietary intake of vitamin D, and serum 25(OH)D concentration among Australian adults residing in Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S), and Hobart (42.8°S). Participants aged 18-75 years were recruited from the Australian Electoral Roll between 2009 and 2010. Measurements were made of height, weight, waist:hip ratio, skin, hair, and eye color, blood pressure, and grip strength. Participants completed a questionnaire on sun exposure and vitamin D intake, together with 10 days of personal UV dosimetry and an associated sun-exposure and physical-activity diary that was temporally linked to a blood test for measurement of 25(OH)D concentration. Ambient solar UV radiation was also monitored at all study sites. We collected comprehensive, high-quality data from 1,002 participants (459 males, 543 females) assessed simultaneously across a range of latitudes and through all seasons. Here we describe the scientific and methodological issues considered in designing the AusD Study. PMID:23524036

  4. Predictors of Vitamin D-Containing Supplement Use in the Australian Population and Associations between Dose and Serum 25-Hydroxyvitamin D Concentrations

    PubMed Central

    Black, Lucinda J.; Jacoby, Peter; Nowson, Caryl A.; Daly, Robin M.; Lucas, Robyn M.

    2016-01-01

    Despite concerns about vitamin D deficiency in the Australian population, little is known about the prevalence and predictors of vitamin D-containing supplement use. We described the use of vitamin D-containing supplements, and investigated associations between supplemental vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D) concentrations, using a single 24-h dietary recall from the 2011–2013 Australian Health Survey (n = 12,153; ages ≥ 2 years). Multiple regression models were used to investigate predictors of vitamin D-containing supplement use in adults, and associations between dose and serum 25(OH)D concentrations/vitamin D sufficiency (≥50 nmol/L), adjusting for potential confounders. The prevalence of vitamin D-containing supplement use was 10%, 6% and 19% in children, adolescents and adults, respectively. Predictors of vitamin D-containing supplement use in adults included being female, advancing age, higher educational attainment, higher socio-economic status, not smoking, and greater physical activity. After adjusting for potential confounders, a 40 IU (1 µg) increase in vitamin D intake from supplements was associated with an increase of 0.41 nmol/L in serum 25(OH)D concentrations (95% CI 0.35, 0.47; p < 0.001). However, the prevalence of vitamin D-containing supplement use was generally low in the Australian population, particularly for single vitamin D supplements, with most supplement users obtaining only low levels of vitamin D from other supplement types. PMID:27338462

  5. Maternal Hypercalcemia Due to Failure of 1,25-Dihydroxyvitamin-D3 Catabolism in a Patient With CYP24A1 Mutations

    PubMed Central

    Hsiao, Edward C.; O'Donnell, Betsy; Salmeen, Kirsten; Nussbaum, Robert; Krebs, Michael; Baumgartner-Parzer, Sabina; Kaufmann, Martin; Jones, Glenville; Bikle, Daniel D.; Wang, YongMei; Mathew, Allen S.; Shoback, Dolores; Block-Kurbisch, Ingrid

    2015-01-01

    Context: Calcium metabolism changes in pregnancy and lactation to meet fetal needs, with increases in 1,25-dihydroxyvitamin D [1,25-(OH)2D] during pregnancy playing an important role. However, these changes rarely cause maternal hypercalcemia. When maternal hypercalcemia occurs, further investigation is essential, and disorders of 1,25-(OH)2D catabolism should be carefully considered in the differential diagnosis. Case: A patient with a childhood history of recurrent renal stone disease and hypercalciuria presented with recurrent hypercalcemia and elevated 1,25-(OH)2D levels during pregnancy. Laboratory tests in the fourth pregnancy showed suppressed PTH, elevated 1,25-(OH)2D, and high-normal 25-hydroxyvitamin D levels, suggesting disordered vitamin D metabolism. Analysis revealed low 24,25-dihydroxyvitamin D3 and high 25-hydroxyvitamin D3 levels, suggesting loss of function of CYP24A1 (25-hydroxyvitamin-D3-24-hydroxylase). Gene sequencing confirmed that she was a compound heterozygote with the E143del and R396W mutations in CYP24A1. Conclusions: This case broadens presentations of CYP24A1 mutations and hypercalcemia in pregnancy. Furthermore, it illustrates that patients with CYP24A1 mutations can maintain normal calcium levels during the steady state but can develop hypercalcemia when challenged, such as in pregnancy when 1,25-(OH)2D levels are physiologically elevated. PMID:26097993

  6. Supplemental vitamin D increases serum cytokines in those with initially low 25-hydroxyvitamin D: a randomized, double blind, placebo-controlled study.

    PubMed

    Barker, Tyler; Rogers, Victoria E; Levy, Mark; Templeton, Jenna; Goldfine, Howard; Schneider, Erik D; Dixon, Brian M; Henriksen, Vanessa T; Weaver, Lindell K

    2015-02-01

    The purpose of this study was to determine if vitamin D status before supplementation influences the cytokine response after supplemental vitamin D. Forty-six reportedly healthy adults (mean(SD); age, 32(7) y; body mass index (BMI), 25.3(4.5) kg/m(2); serum 25-hydroxyvitamin D (25(OH)D), 34.8(12.2) ng/mL) were randomly assigned (double blind) to one of three groups: (1) placebo (n=15), or supplemental vitamin D (cholecalciferol) at (2) 4000 (n=14) or (3) 8000IU (n=17). Supplements were taken daily for 35days. Fasting blood samples were obtained before (Baseline, Bsl) and 35-days after (35-d) supplementation. Serum 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), cytokines, and intact parathyroid hormone with calcium were measured in each blood sample. Supplemental vitamin D increased serum 25(OH)D (4000IU, ≈29%; 8000IU, ≈57%) and 1,25(OH)D (4000IU, ≈12%; 8000IU, ≈38%) without altering intact parathyroid hormone or calcium. The vitamin D metabolite increases in the supplemental vitamin D groups (n=31) were dependent on initial levels as serum 25(OH)D (r=-0.63, p<0.05) and 1,25(OH)D (r=-0.45, p<0.05) at Bsl correlated with their increases after supplementation. Supplemental vitamin D increased interferon (IFN)-γ and interleukin (IL)-10 in subjects that were vitamin D insufficient (serum 25(OH)D<29ng/mL) compared to sufficient (serum 25(OH)D⩾30ng/mL) at Bsl. We conclude that supplemental vitamin D increase a pro- and anti-inflammatory cytokine in those with initially low serum 25(OH)D. PMID:25461390

  7. Changes in vitamin D supplement use and baseline plasma 25-hydroxyvitamin D concentration predict 5-y change in concentration in postmenopausal women.

    PubMed

    Kluczynski, Melissa A; Wactawski-Wende, Jean; Platek, Mary E; DeNysschen, Carol A; Hovey, Kathleen M; Millen, Amy E

    2012-09-01

    Few studies have prospectively examined predictors of change in plasma concentrations of 25-hydroxyvitamin D [25(OH)D]. We sought to determine the predictors of 5-y change in 25(OH)D. Plasma 25(OH)D concentrations were assessed at baseline (1997-2000) and 5 y later (2002-2005) in 668 postmenopausal women enrolled in the Osteoporosis and Periodontal Disease Study. Baseline and changes in demographic, dietary, lifestyle, and health-related factors were tested as predictors of change in 25(OH)D concentrations by using multivariable linear regression. The mean 5-y change in 25(OH)D (mean ± SD) was 7.7 ± 0.7 nmol/L (P < 0.001). In our predictive model (n = 643), predictors explained 31% of the variance in change in 25(OH)D concentrations and included baseline 25(OH)D, baseline and change in vitamin D supplementation and physical activity, change in season of blood draw, BMI, whole-body T score, and baseline hormone therapy use. Baseline 25(OH)D and change in vitamin D supplementation explained the most variation (25%) in 25(OH)D. Exploratory analyses showed a borderline significant interaction between tertiles of baseline 25(OH)D and change in vitamin D supplementation over time (P = 0.06). The greatest mean increase in 25(OH)D (22.9 ± 16.8 nmol/L), with adjustment for other statistically significant predictors, occurred in women whose baseline 25(OH)D concentration was ≤51.0 nmol/L (tertile 1) and who increased supplementation use over time. These results confirm the importance of supplementation in increasing 25(OH)D concentrations in aging women, even after other statistically significant predictors are controlled for. These data also suggest that this is especially true among aging women with inadequate 25(OH)D (e.g., <50 nmol/L). PMID:22833661

  8. Serum 25-hydroxyvitamin D, vitamin D binding protein, and risk of colorectal cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

    PubMed Central

    Weinstein, Stephanie J.; Purdue, Mark P.; Smith-Warner, Stephanie A.; Mondul, Alison M.; Black, Amanda; Ahn, Jiyoung; Huang, Wen-Yi; Horst, Ronald L.; Kopp, William; Rager, Helen; Ziegler, Regina G.; Albanes, Demetrius

    2014-01-01

    The potential role of vitamin D in cancer prevention has generated substantial interest, and laboratory experiments indicate several anti-cancer properties for vitamin D compounds. Prospective studies of circulating 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, suggest an inverse association with colorectal cancer risk, but with some inconsistencies. Furthermore, the direct or indirect impact of the key transport protein, vitamin D binding protein (DBP), has not been examined. We conducted a prospective study of serum 25(OH)D and DBP concentrations and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, based on 476 colorectal cancer cases and 476 controls, matched on age, sex, race, and date of serum collection. All subjects underwent sigmoidoscopic screening at baseline and once during follow-up. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Circulating 25(OH)D was inversely associated with colorectal cancer (OR=0.60, 95% CI 0.38-0.94 for highest versus lowest quintile, p-trend 0.01). Adjusting for recognized colorectal cancer risk factors and accounting for seasonal vitamin D variation did not alter the findings. Neither circulating DBP nor the 25(OH)D:DBP molar ratio, a proxy for free circulating 25(OH)D, was associated with risk (OR=0.82, 95% CI 0.54-1.26, and OR=0.79, 95% CI 0.52-1.21, respectively), and DBP did not modify the 25(OH)D association. The current study eliminated confounding by colorectal cancer screening behavior, and supports an association between higher vitamin D status and substantially lower colorectal cancer risk, but does not indicate a direct or modifying role for DBP. PMID:25156182

  9. Seasonal variation in the serum 25-hydroxyvitamin D levels of young and elderly active and inactive adults in São Paulo, Brazil

    PubMed Central

    Maeda, Sergio Setsuo; Saraiva, Gabriela Luporini; Hayashi, Lilian Fukusima; Cendoroglo, Maysa Seabra; Ramos, Luiz Roberto; Corrêa, Marcelo de Paula; Henrique de Mesquita, Carlos; Lazaretti-Castro, Marise

    2013-01-01

    Objective: To evaluate the 25-hydroxyvitamin D [25(OH)D] concentrations in individuals in the city of São Paulo belonging to different age groups and exhibiting specific behavioral characteristics and to correlate the 25(OH)D concentration with the level of UV radiation (UVR). Patients and Methods: A total of 591 individuals were included, distributed as follows: 177 were living in institutions (NURSING, 76.2 ± 9.0 y old), 243 were part of the community elderly (COMMUNITY, 79.6 ± 5.3 y old), 99 were enrolled in a physical activity program targeting the elderly (ACTIVE, 67.6 ± 5.4 y old) and 72 were young (YOUNG, 23.9 ± 2.8 y old). Blood samples from all individuals were collected throughout the year. UVR measurements were taken by an official meteorology institution. Results: The UVR values varied throughout the year, following a sinusoidal-like pattern. Because of the Earth’s orbit, we hypothesized that there would be cyclic patterns for the 25(OH)D and UVR values that repeat every 12 mo. The general formula is represented by the equation P1+P2⋅sin(−2⋅π12⋅(t−P3)) The mean 25(OH)D concentration and the amplitude of the variation were significantly higher for the YOUNG and ACTIVE groups than for the COMMUNITY and NURSING groups. The nadir for UVR was in June, whereas the nadir for the 25(OH)D concentration was in the spring, corresponding to a delay of one season. Conclusions: There was seasonal variation in the 25(OH)D concentration for all the groups studied; however, the amplitude of the variation was higher for the groups of young and physically active people, possibly due to the higher level of sunlight exposure for these groups. The lowest 25(OH)D concentration was detected in the spring. PMID:24494057

  10. Role of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D level in Egyptian female patients with systemic lupus erythematosus.

    PubMed

    Emerah, Ahmed A; El-Shal, Amal S

    2013-11-01

    Recently, several studies have demonstrated the role of vitamin D receptor (VDR) polymorphisms in the development of systemic lupus erythematosus (SLE). We aimed to evaluate VDR (ApaI, BsmI, and FokI) gene polymorphisms and haplotypes as a risk factors and/or activity markers for SLE, and whether they influence 25-hydroxyvitamin (25(OH) D) level. One hundred and seven SLE patients and 129 controls were enrolled in this study. Disease activity in SLE patients was assessed using Disease Activity Index. Polymorphisms of VDR gene were detected using polymerase chain reaction restriction fragment length polymorphism. Serum 25(OH) D levels were measured using ELISA. We found that ApaI AA genotype, BsmI B allele, Bb, BB genotypes, FokI F allele and FF genotype frequencies of VDR were increased in SLE group. There were significant associations of VDR ApaI AA, BsmI BB, and FokI FF genotypes with lupus nephritis and higher SLE activity scores. Moreover, serum 25(OH) D levels were increased in SLE patients carrying FokI ff genotype compared with patients carrying FF genotype. VDR haplotypes aBF and ABF were associated with SLE risk. The ABF haplotype was associated with higher SLE activity scores and lower serum 25(OH) D concentrations. We observed that the presence of leuko/lymphopenia, renal disorders, higher SLE activity scores and higher anti-dsDNA levels were accompanied by a significant decrease of serum 25(OH)D concentrations. We concluded that The VDR genes polymorphisms, haplotypes, and decreased 25(OH) D levels were associated with risk and more activity scores of SLE.

  11. The Effect of Changing Serum 25-Hydroxyvitamin D Concentrations on Metabolic Syndrome: A Longitudinal Analysis of Participants of a Preventive Health Program.

    PubMed

    Pham, Truong-Minh; Ekwaru, John Paul; Setayeshgar, Solmaz; Veugelers, Paul J

    2015-08-28

    Several studies have shown that a poor vitamin D status may increase the risk of developing metabolic syndrome, which leaves the question whether improving one's vitamin D status may reduce the risk for the syndrome. Here we investigate the effect of temporal changes in serum 25-hydroxyvitamin D (25(OH)D) concentrations on metabolic syndrome among Canadians enrolled in a preventive health program that promotes vitamin D supplementation. We accessed and analyzed data of 6682 volunteer participants with repeated observations on serum 25(OH)D concentrations and metabolic syndrome. We applied logistic regression to quantify the independent contribution of baseline serum 25(OH)D and temporal increases in serum 25(OH)D to the development of metabolic syndrome. In the first year in the program, participants, on average, increased their serum 25(OH)D concentrations by 37 nmol/L. We observed a statistical significant inverse relationship of increases in serum 25(OH)D with risk for metabolic syndrome. Relative to those without improvements, those who improved their serum 25(OH)D concentrations with less 25 nmol/L, 25 to 50 nmol/L, 50 to 75 nmol/L, and more 75 nmol/L had respectively 0.76, 0.64, 0.59, 0.56 times the risk for metabolic syndrome at follow up. These estimates were independent of the effect of baseline serum 25(OH)D concentrations on metabolic syndrome. Improvement of vitamin D status may help reduce the public health burden of metabolic syndrome, and potential subsequent health conditions including type 2 diabetes and cardiovascular disease.

  12. The Relationship Between Serum 25-Hydroxyvitamin D Levels and Nuclear Cataract in the Carotenoid Age-Related Eye Study (CAREDS), an Ancillary Study of the Women's Health Initiative

    PubMed Central

    Rao, Prethy; Millen, Amy E.; Meyers, Kristin J.; Liu, Zhe; Voland, Rickie; Sondel, Sheri; Tinker, Lesley; Wallace, Robert B.; Blodi, Barbara A.; Binkley, Neil; Sarto, Gloria; Robinson, Jennifer; LeBlanc, Erin; Mares, Julie A.

    2015-01-01

    Purpose. To investigate the relationship between serum 25-hydroxyvitamin D (25[OH]D) levels and nuclear cataract among participants of the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative (WHI) Observational Study (OS). Methods. Nuclear cataract was assessed from slit lamp photographs (2001–2004) taken 6 years after collecting serum analyzed for 25(OH)D levels at WHI baseline (1994–1998) in 1278 CAREDS participants age 50 to 79 years. Multivariate (age, iris color, smoking, pulse pressure) odds ratios (ORs) for nuclear cataract (nuclear opacities > level 4 or cataract extraction) by quintiles of serum 25(OH)D were estimated using logistic regression. Results. No significant association was observed between serum 25(OH)D and nuclear cataract among women of all ages (age-adjusted OR [95% confidence interval (CI)] 0.97 [0.65–1.45]). However, there was a significant age interaction (P for interaction = 0.04). There were no significant associations in the women 70 years or older. In women younger than 70 years, we observed an inverse association between serum 25(OH)D and nuclear cataract (multivariate adjusted ORs [95% CI] 0.54 [0.29–0.99] and 0.66 [0.36–1.20] for quintiles 4 and 5 vs. 1, respectively; P = 0.03). Further adjustment for 25(OH)D determinants (body mass index, vitamin D intake, and UVB exposure) attenuated this association. Conclusions. Serum 25(OH)D levels were unrelated to nuclear opacities in this study sample. However, exploratory analyses suggest a protective association in women younger than 70 years. Further investigations of the relationship between vitamin D and nuclear lens opacities are warranted. PMID:26132781

  13. 25-Hydroxyvitamin D Insufficiency and Deficiency is Associated With HIV Disease Progression and Virological Failure Post-Antiretroviral Therapy Initiation in Diverse Multinational Settings

    PubMed Central

    Havers, Fiona; Smeaton, Laura; Gupte, Nikhil; Detrick, Barbara; Bollinger, Robert C.; Hakim, James; Kumarasamy, Nagalingeswaran; Andrade, Adriana; Christian, Parul; Lama, Javier R.; Campbell, Thomas B.; Gupta, Amita

    2014-01-01

    Background. Low 25-hydroxyvitamin D (25(OH)D) has been associated with increased HIV mortality, but prospective studies assessing treatment outcomes after combination antiretroviral therapy (cART) initiation in resource-limited settings are lacking. Methods. A case-cohort study (N = 411) was nested within a randomized cART trial of 1571 cART-naive adults in 8 resource-limited settings and the United States. The primary outcome (WHO stage 3/4 disease or death within 96 weeks of cART initiation) was met by 192 cases, and 152 and 29 cases met secondary outcomes of virologic and immunologic failure. We studied prevalence and risk factors for baseline low 25(OH)D (<32 ng/mL) and examined associated outcomes using proportional hazard models. Results. Low 25(OH)D prevalence was 49% and ranged from 27% in Brazil to 78% in Thailand. Low 25(OH)D was associated with high body mass index (BMI), winter/spring season, country-race group, and lower viral load. Baseline low 25(OH)D was associated with increased risk of human immunodeficiency virus (HIV) progression and death (adjusted hazard ratio (aHR) 2.13; 95% confidence interval [CI], 1.09–4.18) and virologic failure (aHR 2.42; 95% CI, 1.33–4.41). Conclusions. Low 25(OH)D is common in diverse HIV-infected populations and is an independent risk factor for clinical and virologic failure. Studies examining the potential benefit of vitamin D supplementation among HIV patients initiating cART are warranted. PMID:24799602

  14. Serum 25-hydroxyvitamin D levels and incident diabetes mellitus type 2: a competing risk analysis in a large population-based cohort of older adults.

    PubMed

    Schöttker, Ben; Herder, Christian; Rothenbacher, Dietrich; Perna, Laura; Müller, Heiko; Brenner, Hermann

    2013-03-01

    Plausible mechanisms of how vitamin D deficiency may contribute to the development of diabetes mellitus have been proposed but longitudinal cohort studies have yielded heterogeneous results. In 7,791 initially diabetes-free participants of a German population-based cohort, aged 50-74 years, adjusted Cox regression models were employed to estimate hazard ratios (HR) with 95 % confidence intervals (CI) for the association of serum 25-hydroxyvitamin D (25(OH)D) quintiles and incident diabetes. Dose-response relationships were assessed with restricted cubic spline curves. Additionally, analyses accounting for the competing risks of diabetes and death were performed. During 8 years of follow-up, 829 study participants developed diabetes. In women, diabetes risk was significantly increased in the lowest 25(OH)D quintile (HR, 1.38; 1.09-1.75) and non-significantly increased in the 2nd quintile (HR, 1.24; 0.98-1.55) compared to women in 25(OH)D quintiles 3-5. The dose-response relationship showed a non-linear inverse association with risk starting to increase at 25(OH)D levels below 70 nmol/L (statistically significant: below 40 nmol/L). In men, 25(OH)D levels were not associated with diabetes incidence. Renal dysfunction was an effect modifier with a more than doubled diabetes risk in 25(OH)D quintile 1 and an about 1.5-fold risk in quintile 2 compared to quintiles 3-5 if subjects had renal dysfunction. The observed associations were not influenced by the competing risk of death. In this large cohort study of older adults, serum 25(OH)D levels were inversely associated with incident diabetes in women but not in men. The association was particularly strong in subjects with renal dysfunction.

  15. The Influence of Health and Lifestyle Characteristics on the Relation of Serum 25-Hydroxyvitamin D With Risk of Colorectal and Breast Cancer in Postmenopausal Women

    PubMed Central

    Neuhouser, Marian L.; Manson, JoAnn E.; Millen, Amy; Pettinger, Mary; Margolis, Karen; Jacobs, Elizabeth T.; Shikany, James M.; Vitolins, Mara; Adams-Campbell, Lucile; Liu, Simin; LeBlanc, Erin; Johnson, Karen C.; Wactawski-Wende, Jean

    2012-01-01

    The authors’ objective was to discern whether lifestyle or health-related factors were confounders, effect modifiers, or irrelevant with regard to understanding observational associations of serum 25-hydroxyvitamin D (25(OH)D) with colorectal and breast cancer. The authors conducted nested case-control studies of colorectal cancer (310 cases, 310 controls) and breast cancer (1,080 cases, 1,080 controls) in the Women’s Health Initiative Calcium and Vitamin D Clinical Trial (1994–2005). Case-control matching factors included age, latitude, race/ethnicity, and blood collection date. Serum 25(OH)D was assayed in baseline fasting blood. Conditional logistic regression was used to estimate odds ratios for each cancer by serum 25(OH)D concentration, comparing the relative effects of successively adding body mass index, physical activity, and other health and lifestyle characteristics particular to each cancer. In models with matching factors only, low (vs. high) serum 25(OH)D was associated with a colorectal cancer odds ratio of 2.72 (95% confidence interval (CI): 1.55, 4.77) and a breast cancer odds ratio of 1.33 (95% CI: 1.02, 1.72). In multivariate-adjusted models for colorectal cancer, the association strengthened (OR = 4.45, 95% CI: 1.96, 10.10). However, in multivariate-adjusted breast cancer models, associations were no longer significant (OR = 1.06, 95% CI: 0.78, 1.43). Adjusting for health and lifestyle characteristics has differential effects depending on the cancer site; when modeling such relations, investigators should take these factors into account. PMID:22362582

  16. Optimal Vitamin D Supplementation Doses that Minimize the Risk for Both Low and High Serum 25-Hydroxyvitamin D Concentrations in the General Population

    PubMed Central

    Veugelers, Paul J.; Pham, Truong-Minh; Ekwaru, John Paul

    2015-01-01

    The Recommended Dietary Allowance (RDA) is the nutrient intake considered to be sufficient to meet the requirements of 97.5% of the population. Recent reports revealed a statistical error in the calculation of the RDA for vitamin D opening the question of what the recommendation should be. We took a dual approach to answer this question: (1) we aggregated 108 published estimates on vitamin D supplementation and vitamin D status; and (2) we analyzed 13,987 observations of program participants. The aggregation of published data revealed that 2909 IU of vitamin D per day is needed to achieve serum 25-hydroxyvitamin D (25(OH)D) concentrations of 50 nmol/L or more in 97.5% of healthy individuals. For normal weight, overweight and obese program participants this was 3094, 4450 and 7248 IU respectively. These supplementation doses would also result in 2.5% of normal weight, overweight and obese participants having 25(OH)D concentrations above 210, 200 and 214 nmol/L respectively. As these concentrations are high, an approach that minimizes the risk for both low and high concentrations seems desirable. With this approach we estimated, for example, that doses of 1885, 2802 and 6235 IU per day are required for normal weight, overweight and obese individuals respectively to achieve natural 25(OH)D concentrations (defined as 58 to 171 nmol/L). In conclusion, the large extent of variability in 25(OH)D concentrations makes a RDA for vitamin D neither desirable nor feasible. We therefore propose recommendations be articulated in the form of an optimal intake that minimizes the risk for both low and high serum 25(OH)D concentrations. This contribution includes body weight specific recommendations for optimal intakes for various combinations of lower and upper 25(OH)D concentration targets. PMID:26690210

  17. Standardizing serum 25-hydroxyvitamin D data from four Nordic population samples using the Vitamin D Standardization Program protocols: Shedding new light on vitamin D status in Nordic individuals.

    PubMed

    Cashman, Kevin D; Dowling, Kirsten G; Škrabáková, Zuzana; Kiely, Mairead; Lamberg-Allardt, Christel; Durazo-Arvizu, Ramon A; Sempos, Christopher T; Koskinen, Seppo; Lundqvist, Annamari; Sundvall, Jouko; Linneberg, Allan; Thuesen, Betina; Husemoen, Lise Lotte N; Meyer, Haakon E; Holvik, Kristin; Grønborg, Ida M; Tetens, Inge; Andersen, Rikke

    2015-11-01

    Knowledge about the distributions of serum 25-hydroxyvitamin D (25(OH)D) concentrations in representative population samples is critical for the quantification of vitamin D deficiency as well as for setting dietary reference values and food-based strategies for its prevention. Such data for the European Union are of variable quality making it difficult to estimate the prevalence of vitamin D deficiency across member states. As a consequence of the widespread, method-related differences in measurements of serum 25(OH)D concentrations, the Vitamin D Standardization Program (VDSP) developed protocols for standardizing existing serum 25(OH)D data from national surveys around the world. The objective of the present work was to apply the VDSP protocols to existing serum 25(OH)D data from a Danish, a Norwegian, and a Finnish population-based health survey and from a Danish randomized controlled trial. A specifically-selected subset (n 100-150) of bio-banked serum samples from each of the studies were reanalyzed for 25(OH)D by LC-MS/MS and a calibration equation developed between old and new 25(OH)D data, and this equation was applied to the entire data-sets from each study. Compared to estimates based on the original serum 25(OH)D data, the percentage vitamin D deficiency (< 30 nmol/L) decreased by 21.5% in the Danish health survey but by only 1.4% in the Norwegian health survey; but was relatively unchanged (0% and 0.2%) in the Finish survey or Danish RCT, respectively, following VDSP standardization. In conclusion, standardization of serum 25(OH)D concentrations is absolutely necessary in order to compare serum 25(OH)D concentrations across different study populations, which is needed to quantify and prevent vitamin D deficiency.

  18. Optimal Vitamin D Supplementation Doses that Minimize the Risk for Both Low and High Serum 25-Hydroxyvitamin D Concentrations in the General Population.

    PubMed

    Veugelers, Paul J; Pham, Truong-Minh; Ekwaru, John Paul

    2015-12-04

    The Recommended Dietary Allowance (RDA) is the nutrient intake considered to be sufficient to meet the requirements of 97.5% of the population. Recent reports revealed a statistical error in the calculation of the RDA for vitamin D opening the question of what the recommendation should be. We took a dual approach to answer this question: (1) we aggregated 108 published estimates on vitamin D supplementation and vitamin D status; and (2) we analyzed 13,987 observations of program participants. The aggregation of published data revealed that 2909 IU of vitamin D per day is needed to achieve serum 25-hydroxyvitamin D (25(OH)D) concentrations of 50 nmol/L or more in 97.5% of healthy individuals. For normal weight, overweight and obese program participants this was 3094, 4450 and 7248 IU respectively. These supplementation doses would also result in 2.5% of normal weight, overweight and obese participants having 25(OH)D concentrations above 210, 200 and 214 nmol/L respectively. As these concentrations are high, an approach that minimizes the risk for both low and high concentrations seems desirable. With this approach we estimated, for example, that doses of 1885, 2802 and 6235 IU per day are required for normal weight, overweight and obese individuals respectively to achieve natural 25(OH)D concentrations (defined as 58 to 171 nmol/L). In conclusion, the large extent of variability in 25(OH)D concentrations makes a RDA for vitamin D neither desirable nor feasible. We therefore propose recommendations be articulated in the form of an optimal intake that minimizes the risk for both low and high serum 25(OH)D concentrations. This contribution includes body weight specific recommendations for optimal intakes for various combinations of lower and upper 25(OH)D concentration targets.

  19. Why the minimum desirable serum 25-hydroxyvitamin D level should be 75 nmol/L (30 ng/ml).

    PubMed

    Vieth, Reinhold

    2011-08-01

    The Institutes of Medicine (IOM) recently revised the recommended dietary allowances (RDA) for vitamin D, to maintain serum 25-hydroxyvitamin D (25(OH)D) at or above 50 nmol/L, to sustain bone density, calcium absorption, and to minimize risk of osteomalacia and rickets. However there are compelling reasons why 25(OH)D should preferably exceed 75 nmol/L: (A) Scrutiny of actual data specified by the IOM relating 25(OH)D to bone density and osteomalacia shows the desirable minimum 25(OH)D to be 75 nmol/L (30 ng/mL). (B) Humans are primates, optimized through evolution to inhabit tropical latitudes, with serum 25(OH)D over 100 nmol/L. (C) Epidemiologic relationships show health benefits if 25(OH)D levels exceed 70 nmol/L; these include fewer falls, better tooth attachment, less colorectal cancer, improved depression and wellbeing. Some studies of populations at high-latitude relate higher 25(OH)D to risk of prostate cancer, pancreatic cancer or mortality. Those relationships are attributable to the dynamic fluctuations in 25(OH)D specific to high latitudes, and which can be corrected by maintaining 25(OH)D at steady, high levels throughout the year, the way they are in the tropics. (D) There are now many clinical trials that show benefits and/or no adversity with doses of vitamin D that raise serum 25(OH)D to levels beyond 75 nmol/L. Together, the evidence makes it very unlikely that further research will change the conclusion that risk of disease with serum 25(OH)D higher than 75 nmol/L is lower than the risk of disease if the serum 25(OH)D is approximately 53 nmol/L. PMID:21872808

  20. Midgestation maternal serum 25-hydroxyvitamin D level and soluble fms-like tyrosine kinase 1/placental growth factor ratio as predictors of severe preeclampsia.

    PubMed

    Woodham, Padmashree Chaudhury; Brittain, Julia E; Baker, Arthur M; Long, D Leann; Haeri, Sina; Camargo, Carlos A; Boggess, Kim A; Stuebe, Alison M

    2011-12-01

    Recent studies have shown that low serum 25-hydroxyvitamin D (25[OH]D) level is a risk factor for preeclampsia. The clinical significance of in vitro findings that vitamin D regulates vascular endothelial growth factor production is unclear. We sought to determine whether there is an association between midgestation serum 25(OH)D levels and angiogenic factor activity and to compare their predictive value for the development of severe preeclampsia. We conducted a nested case-control study of women with severe preeclampsia (n=41) versus women with uncomplicated term birth (n=123) who had second trimester genetic screening (15-20 weeks). Using banked frozen serum, we measured levels of 25(OH)D, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, and placental growth factor and compared their correlations and predictive values. We found no correlation between serum 25(OH)D and angiogenic factors levels. 25(OH)D alone was comparable to vascular endothelial growth factor and soluble fms-like tyrosine kinase 1/placental growth factor ratio as a predictive marker for severe preeclampsia. A composite of both 25(OH)D level and soluble fms-like tyrosine kinase 1/placental growth factor ratio was more predictive than either alone (area under curve: 0.83 versus 0.74 and 0.67, respectively). In conclusion, combining midpregnancy 25(OH)D level with soluble fms-like tyrosine kinase 1/placental growth factor ratio provides a better prediction for the development of severe preeclampsia. PMID:21986503

  1. Vitamin D Intake and Season Modify the Effects of the GC and CYP2R1 Genes on 25-Hydroxyvitamin D Concentrations123

    PubMed Central

    Engelman, Corinne D.; Meyers, Kristin J.; Iyengar, Sudha K.; Liu, Zhe; Karki, Chitra K.; Igo, Robert P.; Truitt, Barbara; Robinson, Jennifer; Sarto, Gloria E.; Wallace, Robert; Blodi, Barbara A.; Klein, Michael L.; Tinker, Lesley; LeBlanc, Erin S.; Jackson, Rebecca D.; Song, Yiqing; Manson, JoAnn E.; Mares, Julie A.; Millen, Amy E.

    2013-01-01

    Vitamin D deficiency {defined by the blood concentration of 25-hydroxyvitamin D [25(OH)D]} has been associated with many adverse health outcomes. Genetic and nongenetic factors account for variation in 25(OH)D, but the role of interactions between these factors is unknown. To assess this, we examined 1204 women of European descent from the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women’s Health Initiative Observational Study. Twenty-nine single nucleotide polymorphisms (SNPs) in 4 genes, GC, CYP2R1, DHCR7, and CYP24A1, from recent meta-analyses of 25(OH)D genome-wide association studies were genotyped. Associations between these SNPs and 25(OH)D were tested using generalized linear regression under an additive genetic model adjusted for age, blood draw month, and ancestry. Results were stratified by season of blood draw and, separately, vitamin D intake for the 6 SNPs showing a significant association with 25(OH)D at the P < 0.01 level. Two nonsynonymous SNPs in GC and 4 SNPs in CYP2R1 were strongly associated with 25(OH)D in individuals whose blood was drawn in summer (P ≤ 0.002) but not winter months and, independently, in individuals with vitamin D intakes ≥400 (P ≤ 0.004) but not <400 IU/d (10 μg/d). This effect modification, if confirmed, has important implications for the design of genetic studies for all health outcomes and for public health recommendations and clinical practice guidelines regarding the achievement of adequate vitamin D status. PMID:23190755

  2. Short communication: artificial ultraviolet B light exposure increases vitamin D levels in cow plasma and milk.

    PubMed

    Jakobsen, Jette; Jensen, Søren Krogh; Hymøller, Lone; Andersen, Elisabeth Wreford; Kaas, Poul; Burild, Anders; Jäpelt, Rie Bak

    2015-09-01

    The number of dairy cows without access to pasture or sunlight is increasing; therefore, the content of vitamin D in dairy products is decreasing. Ultimately, declining vitamin D levels in dairy products will mean that dairy products are a negligible source of natural vitamin D for humans. We tested the ability of a specially designed UVB lamp to enhance the vitamin D3 content in milk from dairy cows housed indoors. This study included 16 cows divided into 4 groups. Each group was exposed daily to artificial UVB light simulating 1, 2, 3, or 4 h of summer sun at 56°N for 24 d, and the group with simulated exposure to 2 h of summer sun daily continued to be monitored for 73 d. We found a significant increase in 25-hydroxyvitamin D3 (25OHD3) levels in plasma as well as vitamin D3 and 25OHD3 levels in milk after daily exposure for 24 d in all treatment groups. Extending daily exposure to artificial UVB light to 73 d did not lead to an increase of vitamin D3 or 25OHD3 level in the milk. In conclusion, the change in production facilities for dairy cows providing cows with no access to pasture and sunlight causes a decrease of vitamin D levels in dairy products. This decrease may be prevented by exposing cows to artificial UVB light in the stable. PMID:26117346

  3. Short communication: artificial ultraviolet B light exposure increases vitamin D levels in cow plasma and milk.

    PubMed

    Jakobsen, Jette; Jensen, Søren Krogh; Hymøller, Lone; Andersen, Elisabeth Wreford; Kaas, Poul; Burild, Anders; Jäpelt, Rie Bak

    2015-09-01

    The number of dairy cows without access to pasture or sunlight is increasing; therefore, the content of vitamin D in dairy products is decreasing. Ultimately, declining vitamin D levels in dairy products will mean that dairy products are a negligible source of natural vitamin D for humans. We tested the ability of a specially designed UVB lamp to enhance the vitamin D3 content in milk from dairy cows housed indoors. This study included 16 cows divided into 4 groups. Each group was exposed daily to artificial UVB light simulating 1, 2, 3, or 4 h of summer sun at 56°N for 24 d, and the group with simulated exposure to 2 h of summer sun daily continued to be monitored for 73 d. We found a significant increase in 25-hydroxyvitamin D3 (25OHD3) levels in plasma as well as vitamin D3 and 25OHD3 levels in milk after daily exposure for 24 d in all treatment groups. Extending daily exposure to artificial UVB light to 73 d did not lead to an increase of vitamin D3 or 25OHD3 level in the milk. In conclusion, the change in production facilities for dairy cows providing cows with no access to pasture and sunlight causes a decrease of vitamin D levels in dairy products. This decrease may be prevented by exposing cows to artificial UVB light in the stable.

  4. Increases in summer serum 25-hydroxyvitamin D (25OHD) concentrations in elderly subjects in São Paulo, Brazil vary with age, gender and ethnicity

    PubMed Central

    2010-01-01

    Background Hypovitaminosis D is a common condition among elderly individuals in temperate-climate countries, with a clear seasonal variation on 25 hydroxyvitamin D levels, increasing after summer and decreasing after winter, but there are few data from sunny countries such as Brazil. Many factors can interfere on vitamin D cutaneous synthesis. We aimed at studying the 25OHD variations during winter and summer in an outdoor physically active elderly population living in São Paulo city, and analysed their determining factors. Methods Ninety-nine individuals (52 women and 47 men, from 55 to 83 years old) from different ethnic groups were selected from an outdoor physical activity group. Data are reported as Mean ± SD, and we used Pearson Linear Correlation, Student's t-test for non-related samples, Chi-square (χ²) test and One-way ANOVA for analysis. Results Mean 25OHD value for the whole group was 78.9 ± 30.9 nmol/L in the winter and 91.6 ± 31.7 nmol/L in the summer (p = 0.005). Mean winter serum 25OHD concentrations were not different between men and women (81.2 ± 30.1 nmol/L vs. 76.7 ± 31.8 nmol/L, respectively), and 19.2% of the individuals showed values < 50 nmol/L. In the summer, we noticed an increase only for men (107.6 ± 31.4 nmol/L) compared to women (76.7 ± 24.0 nmol/L), and 6.5% showed values < 50 nmol/L. A decrease in the mean PTH in the summer compared to the winter was noticed, with PTH levels showing a relationship with 25OHD concentrations only in the winter (r = -0.208, p = 0.041). White individuals showed an increase in mean serum 25OHD in the summer (p = 0.016) which was not noticed for other ethnic groups (Asians, native Brazilians and blacks). An increase in 25OHD values in the summer was observed in the age groups ranging from 51-60 and 61-70 years old (p < 0.05), but not in the age group from 71 years old on. Conclusions 25OHD values increased during the summer in elderly residents of São Paulo, but to different extents depending on

  5. Low 25-Hydroxyvitamin D Concentrations Predict Incident Depression in Well-Functioning Older Adults: The Health, Aging, and Body Composition Study

    PubMed Central

    Sink, Kaycee M.; Tooze, Janet A.; Atkinson, Hal H.; Cauley, Jane A.; Yaffe, Kristine; Tylavsky, Frances A.; Rubin, Susan M.; Simonsick, Eleanor M.; Kritchevsky, Stephen B.; Houston, Denise K.

    2015-01-01

    Background. Cross-sectional studies suggest that low 25-hydroxyvitamin D (25[OH]D) may be a risk factor for depression; however, there are few prospective studies. We examined the association between 25(OH)D and depressive symptoms in community-dwelling persons aged 70–79 years in the Health, Aging, and Body Composition (Health ABC) Study (n = 2598). Methods. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale (CES-D) at baseline and 2-, 3- and 4-year follow-up. Serum 25(OH)D was measured at 1-year follow-up and categorized as <20, 20–<30, and ≥30 ng/mL. Mixed models were used to examine change in CES-D scores according to 25(OH)D categories. The association between 25(OH)D categories and incident depression (CES-D short score ≥10 or antidepressant medication use) were assessed using Cox proportional hazards models. Analyses were adjusted for socio-demographic and behavioral characteristics, season, and chronic conditions. Results. Thirty-three percent of participants had 25(OH)D <20ng/mL. Serum 25(OH)D was not associated with CES-D scores at baseline (p = .51); however, CES-D scores increased over time and were significantly associated with 25(OH)D at 2-year (p = .003) and 4-year follow-up (p < .001). Among 2,156 participants free of depression at the 1-year follow-up, the cumulative incidence of depression was 26.9%. Participants with 25(OH)D <20ng/mL were at greater risk of developing depression (HR [95% CI]: 1.65 [1.23–2.22]) over 4 years of follow-up compared with those with 25(OH)D ≥30ng/mL. Conclusion. Low 25(OH)D was independently associated with a greater increase in depressive symptom scores and incident depression in community-dwelling older adults. PMID:25326643

  6. Impact of Circulating Vitamin D Binding Protein Levels on the Association Between 25-Hydroxyvitamin D and Pancreatic Cancer Risk: A Nested Case-Control Study

    PubMed Central

    Weinstein, Stephanie J.; Stolzenberg-Solomon, Rachael Z.; Kopp, William; Rager, Helen; Virtamo, Jarmo; Albanes, Demetrius

    2012-01-01

    High concentrations of circulating 25-hydroxyvitamin D [25(OH)D] have been associated with elevated pancreatic cancer risk. As this is contrary to an expected inverse association between vitamin D status and cancer, we examined whether vitamin D binding protein (DBP), the primary carrier of vitamin D compounds in circulation, plays a role in this relationship. Prediagnostic serum DBP and 25(OH)D were studied in relation to risk of pancreatic cancer in a nested case-control study of 234 pancreatic cancer cases and 234 controls in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression, and statistical tests were two-sided. We found that DBP and 25(OH)D were correlated (r=0.27; p<0.0001), and DBP was inversely associated with pancreatic cancer risk (OR=0.66, 95% CI=0.39–1.12, for the highest vs. lowest quartile; p-trend=0.02). Importantly, this association appeared to have a threshold between quartiles 2–4 and quartile 1, and was primarily evident among men with concurrent high 25(OH)D concentrations (OR=0.33, 95% CI=0.16–0.70 for highest vs. lowest quartile; p-trend=0.002), with no association in men with lower serum 25(OH)D (OR=1.28, 95% CI=0.62–2.61 for highest vs. lowest quartile, p-trend 0.63, p-interaction= 0.01). Men with higher 25(OH)D concentrations and serum DBP below the median showed greatly elevated risk of pancreatic cancer (OR=5.01, 95% CI 2.33–10.78, for highest vs. lowest quartile; p-trend < 0.0001), while risk was weakly inversely associated with serum 25(OH)D when DBP concentrations were higher (p-interaction = 0.001). Taken together, our findings indicate that higher DBP concentrations may sequester more 25(OH)D and reduce free 25(OH)D bioavailability. Simultaneous examination of DBP and 25(OH)D may be important in determining the association of vitamin D with cancer risk. PMID:22232734

  7. Circulating 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Concentrations and Postoperative Infections in Cardiac Surgical Patients: The CALCITOP-Study

    PubMed Central

    Zittermann, Armin; Kuhn, Joachim; Ernst, Jana B.; Becker, Tobias; Larisch, Julia; Dreier, Jens; Knabbe, Cornelius; Börgermann, Jochen; Gummert, Jan F.

    2016-01-01

    Background Vitamin D has immunomodulatory properties and seems to reduce the risk of infections. Whether low vitamin D concentrations are independent risk factors for nosocomial postoperative infections in surgical patients remains to be studied in detail. Methods In 3,340 consecutive cardiac surgical patients, we investigated the association of circulating 25-hydroxyvitamin D (25OHD; indicator of nutritional vitamin D status) and 1,25-dihydroxyvitamin D (1,25[OH]2D; active vitamin D hormone) with nosocomicial infections. The primary endpoint was a composite of thoracic wound infection, sepsis, and broncho-pulmonary infection. Vitamin D status was measured on the last preoperative day. Infections were assessed until discharge. Logistic regression analysis was used to examine the association between vitamin D metabolite concentrations and the composite endpoint. Results The primary endpoint was reached by 5.6% (n = 186). In patients who reached and did not reach the endpoint, in-hospital mortality was 13.4% and 1.5%, respectively (P<0.001). Median (IQR) 25OHD and 1,25(OH)2D concentrations were 43. 2 (29.7–61.9) nmol/l and 58.0 (38.5–77.5) pmol/l, respectively. Compared with the highest 1,25(OH)2D quintile (>81.0 pmol/l), the multivariable–adjusted odds ratio of infection was 2.57 (95%CI:1.47–4.49) for the lowest 1,25(OH)2D quintile (<31.5 pmol/l) and 1.85 (95%CI:1.05–3.25) for the second lowest quintile (31.5–49.0 pmol/l). There was no significant association between 25OHD concentrations and the primary endpoint. Conclusions Our data indicate an independent association of low 1,25(OH)2D levels with the risk of postoperative infections in cardiac surgical patients. Future studies should pay more attention on the clinical relevance of circulating 1,25(OH)2D and its regulation. PMID:27355377

  8. Circulating 25-Hydroxyvitamin D, IRS1 Variant rs2943641, and Insulin Resistance: Replication of a Gene–Nutrient Interaction in 4 Populations of Different Ancestries

    PubMed Central

    Zheng, Ju-Sheng; Parnell, Laurence D.; Smith, Caren E.; Lee, Yu-Chi; Jamal-Allial, Aziza; Ma, Yiyi; Li, Duo; Tucker, Katherine L.; Ordovás, José M.; Lai, Chao-Qiang

    2014-01-01

    BACKGROUND Associations of either insulin receptor substrate 1 (IRS1) variants or circulating 25-hydroxyvitamin D [25(OH)D] with type 2 diabetes (T2D) and insulin resistance (IR) are inconsistent. This study sought to determine whether circulating 25(OH)D modulates the association of a potentially functional variant at IRS1 (rs2943641) with insulin resistance. METHOD Interaction between IRS1 rs2943641 and circulating 25(OH)D on homeostasis model assessment for IR (HOMA-IR) was examined in the Boston Puerto Rican Health Study (BPRHS) (n = 1144). Replication was performed in the African-American (n = 1126), non-Hispanic white (n = 1967), and Hispanic (n = 1241) populations of the Multi-Ethnic Study of Atherosclerosis (MESA) with genotypes of 3 IRS1 variants, rs2972144, rs1515104, and rs2673142, which are tag single nucleotide polymorphisms (SNPs) and in strong linkage disequilibrium with rs2943641. RESULTS Higher circulating 25(OH)D was associated with lower risk of T2D and IR in BPRHS women homozygous for minor allele rs2943641T. Consistently, in each of 3 MESA populations, HOMA-IR and insulin decreased more evidently with higher circulating 25(OH)D in women of the rs2943641TT genotype than in carriers of the major allele (rs2943641C). Metaanalysis indicated significant and consistent interactions between circulating 25(OH)D and IRS1 variants on HOMA-IR (log transformed) [pooled β = −0.008, 95% CI: −0.016 to −0.001, P interaction = 0.004] and insulin (log transformed) (pooled β = −0.006, 95% CI: −0.011 to −0.002, P interaction = 0.023) in 3065 women of the 4 populations. CONCLUSIONS Participants with different genotypes of IRS1 rs2943641 exhibit differential benefit from high circulating 25(OH)D for the reduction of insulin resistance and T2D risk. This gene–nutrient interaction, which appears to be limited to women, warrants further examination in randomized controlled trials of vitamin D supplementation. PMID:24255076

  9. Sustained Increase of 25-Hydroxyvitamin D Levels in Healthy Young Women during Wintertime after Three Suberythemal UV Irradiations—The MUVY Pilot Study

    PubMed Central

    Biersack, Maria Gudrun; Hajdukiewicz, Malgorzata; Uebelhack, Ralf; Franke, Leonora; Piazena, Helmut; Klaus, Pascal; Höhne-Zimmer, Vera; Braun, Tanja; Buttgereit, Frank; Burmester, Gerd-Rüdiger; Detert, Jacqueline

    2016-01-01

    Objectives Vitamin D (VitD) deficiency is a health problem prevalent not only in the elderly but also in young adults. The primary objective of our observational pilot study “MUVY” (Mood, UVR, Vitamin D in Young women) was to test both the short-term and long-term effects of a series of three suberythemal UV radiation (UVR) exposures on the VitD status and well-being of young healthy women during winter in a repeat measure design. Methods 20 healthy young women (Fitzpatrick skin types I–III, aged 21–25 years) received three full body broad band UVR exposures with an escalating erythemally weighted dose schedule during one week in winter, and completed self-report questionnaires monitoring symptoms of depression (Beck Depression Inventory, BDI) and affective state/well-being (Profile of Mood States, POMS) at baseline and three days after the last UVR exposure. 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in serum at baseline, and at study days 8, 36 and 50. Results Mean baseline 25(OH)D level was 54.3 nmol/L (standard deviation (s.d.) = 24.1), with seven women having VitD deficient status. Relevant symptoms of depression, as indicated by low BDI total scores (0–8), were absent. After the three UVR exposures the increment of 25(OH)D was an average of 13.9 nmol/L (95% confidence interval (CI) = 9.4–18.4) and 26.2 pmol/L (95%CI = 7.2–45.1) for 1,25(OH)2D. Δ25(OH)D, and corresponding baseline levels were significantly and inversely associated (rho = -0.493, p = 0.027). Only 25(OH)D remained significantly increased above baseline for at least six weeks after the last UVR exposure. A strong inverse correlation of the POMS subscale “Vigor/Activity” and the increment in 1,25(OH)2D was found (rho = -0.739, p<0.001) at day 8. Conclusions Three suberythemal whole body UVR exposures during one week are a simple and suitable method for improving 25(OH)D levels during winter, for at least six weeks, and especially in

  10. Pretreatment Serum Concentrations of 25-Hydroxyvitamin D and Breast Cancer Prognostic Characteristics: A Case-Control and a Case-Series Study

    PubMed Central

    Yao, Song; Sucheston, Lara E.; Millen, Amy E.; Johnson, Candace S.; Trump, Donald L.; Nesline, Mary K.; Davis, Warren; Hong, Chi-Chen; McCann, Susan E.; Hwang, Helena; Kulkarni, Swati; Edge, Stephen B.; O'Connor, Tracey L.; Ambrosone, Christine B.

    2011-01-01

    Background Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity. Methods and Findings In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08–0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22–0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses. Conclusion In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant

  11. Changing Incidence of Serum 25-Hydroxyvitamin D Values Above 50 ng/mL: A 10-Year Population-Based Study

    PubMed Central

    Dudenkov, Daniel V.; Yawn, Barbara P.; Oberhelman, Sara S.; Fischer, Philip R.; Singh, Ravinder J.; Cha, Stephen S.; Maxson, Julie A.; Quigg, Stephanie M.; Thacher, Tom D.

    2015-01-01

    Objective To determine the incidence trend of 25-hydroxyvitamin D [25(OH)D] values >50 ng/mL and associated toxicity. Patients and Methods We conducted a retrospective, population-based study in Olmsted County, MN, from January 1, 2002 through December 31, 2011 (10 years) using the Rochester Epidemiology Project. Individuals were eligible if they resided in Olmsted County, MN, during the study period and had a measured 25(OH)D value >50 ng/mL (>125 nmol/L). The date of the first 25(OH)D value >50 ng/mL was considered the index date for incidence determination. Hypercalcemia, the primary vitamin D toxicity, was considered potentially associated with the 25(OH)D concentration if measured within 3 months of the 25(OH)D measurement, and such cases had medical record review. Results Of 20,308 total 25(OH)D measurements, 1714 (8.4%), 123 (0.6%), and 37 (0.2%) unique persons had 25(OH)D values >50, ≥80, and ≥100 ng/mL, respectively. The age- and sex-adjusted incidence of 25(OH)D values >50 ng/mL increased from 9 to 233 per 100,000 person-years from 2002 to 2011 (P<.001), respectively, and was greatest in persons of age ≥65 years (P<.001) and in females (P<.001). Serum 25(OH)D values were not significantly related with serum calcium values or with the risk of hypercalcemia. Medical record review identified four cases (0.2%) where 25(OH)D values >50 ng/mL were associated temporally with hypercalcemia, but only one had clinical toxicity associated with the highest observed 25(OH)D value of 364 ng/mL. Conclusion The incidence of 25(OH)D values >50 ng/mL increased significantly between 2002 and 2011, without a corresponding increase in acute clinical toxicity. PMID:25939935

  12. Evidence for Threshold Effects of 25-Hydroxyvitamin D on Glucose Tolerance and Insulin Resistance in Black and White Obese Postmenopausal Women12

    PubMed Central

    Sorkin, John D.; Vasaitis, Tadas Sean; Streeten, Elizabeth; Ryan, Alice S.; Goldberg, Andrew P.

    2014-01-01

    We identified normal vs. abnormal 25-hydroxyvitamin D [25(OH)D] concentrations by examining the relation of 25(OH)D to non-bone–related measures (plasma glucose, insulin resistance, lipids, blood pressure, fitness, obesity, and regional adiposity) and asking whether there is a 25(OH)D concentration above and below which the relation between 25(OH)D and outcome changes. We examined the relation between 25(OH)D and outcome by race to see whether race-specific normal ranges are needed, and we examined the role of insulin-like growth factor-1 (IGF-1) in modulating the relation between 25(OH)D and outcome. In a cross-sectional study of 239 overweight and obese, sedentary postmenopausal women without diabetes (83 black, 156 white), outcome measures included plasma lipids, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), IGF-1, parathyroid hormone (PTH), aerobic fitness, body composition, subcutaneous abdominal and visceral fat, and blood pressure. We identified threshold effects in the association between 25(OH)D and these variables using piecewise linear regressions. We found that 25(OH)D was inversely related to fasting glucose, fasting and 2-h insulin, HOMA-IR, visceral abdominal fat, percentage fat, PTH, and triglycerides. Evidence for a threshold effect of 25(OH)D was found for 2-h glucose, 2-h insulin, fasting insulin, and HOMA-IR. There was no evidence suggesting the need for race-specific normal 25(OH)D concentrations. IGF-1 modulated the relation between 25(OH)D and outcome but only below, and not above, a threshold 25(OH)D concentration. Our findings suggest a threshold effect of 25(OH)D on glucose–insulin metabolism such that 25(OH)D ≥ ∼26 μg/L (65.0 pmol/L) supports normal glucose homeostasis and that the same cut point defining normal 25(OH)D concentration can be used in black and white women. This study was registered at clinicaltrials.gov as NCT01798030. PMID:24717362

  13. Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study

    PubMed Central

    McDonnell, Sharon L.; Baggerly, Carole; French, Christine B.; Baggerly, Leo L.; Garland, Cedric F.; Gorham, Edward D.; Lappe, Joan M.; Heaney, Robert P.

    2016-01-01

    Background Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with a lower risk of multiple cancer types across a range of 25(OH)D concentrations. Objectives To investigate whether the previously reported inverse association between 25(OH)D and cancer risk could be replicated, and if a 25(OH)D response region could be identified among women aged 55 years and older across a broad range of 25(OH)D concentrations. Methods Data from two cohorts representing different median 25(OH)D concentrations were pooled to afford a broader range of 25(OH)D concentrations than either cohort alone: the Lappe cohort (N = 1,169), a randomized clinical trial cohort (median 25(OH)D = 30 ng/ml) and the GrassrootsHealth cohort (N = 1,135), a prospective cohort (median 25(OH)D = 48 ng/ml). Cancer incidence over a multi-year period (median: 3.9 years) was compared according to 25(OH)D concentration. Kaplan-Meier plots were developed and the association between 25(OH)D and cancer risk was examined with multivariate Cox regression using multiple 25(OH)D measurements and spline functions. The study included all invasive cancers excluding skin cancer. Results Age-adjusted cancer incidence across the combined cohort (N = 2,304) was 840 cases per 100,000 person-years (1,020 per 100,000 person-years in the Lappe cohort and 722 per 100,000 person-years in the GrassrootsHealth cohort). Incidence was lower at higher concentrations of 25(OH)D. Women with 25(OH)D concentrations ≥40 ng/ml had a 67% lower risk of cancer than women with concentrations <20 ng/ml (HR = 0.33, 95% CI = 0.12–0.90). Conclusions 25(OH)D concentrations ≥40 ng/ml were associated with substantial reduction in risk of all invasive cancers combined. PMID:27049526

  14. Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA)

    PubMed Central

    Shin, Youn Ho; Yu, Jinho; Kim, Kyung Won; Ahn, Kangmo; Hong, Seo-Ah; Lee, Eun; Yang, Song-I; Jung, Young-Ho; Kim, Hyung Young; Seo, Ju-Hee; Kwon, Ji-Won; Kim, Byoung-Ju; Kim, Hyo-Bin; Shim, Jung Yeon; Kim, Woo Kyung; Song, Dae Jin; Lee, So-Yeon; Lee, Soo Young; Jang, Gwang Cheon; Suh, Dong In; Yang, Hyeon-Jong; Kim, Bong Sung; Choi, Suk-Joo; Oh, Soo-Young; Kwon, Ja-Young; Lee, Kyung-Ju; Park, Hee Jin; Lee, Pil Ryang; Won, Hye-Sung

    2013-01-01

    Purpose Previous studies suggest that the concentration of 25-hydroxyvitamin D [25(OH)D] in cord blood may show an inverse association with respiratory tract infections (RTI) during childhood. The aim of the present study was to examine the influence of 25(OH)D concentrations in cord blood on infant RTI in a Korean birth cohort. Methods The levels of 25(OH)D in cord blood obtained from 525 Korean newborns in the prospective COhort for Childhood Origin of Asthma and allergic diseases were examined. The primary outcome variable of interest was the prevalence of RTI at 6-month follow-up, as diagnosed by pediatricians and pediatric allergy and pulmonology specialists. RTI included acute nasopharyngitis, rhinosinusitis, otitis media, croup, tracheobronchitis, bronchiolitis, and pneumonia. Results The median concentration of 25(OH)D in cord blood was 32.0 nmol/L (interquartile range, 21.4 to 53.2). One hundred and eighty neonates (34.3%) showed 25(OH)D concentrations less than 25.0 nmol/L, 292 (55.6%) showed 25(OH)D concentrations of 25.0-74.9 nmol/L, and 53 (10.1%) showed concentrations of ≥75.0 nmol/L. Adjusting for the season of birth, multivitamin intake during pregnancy, and exposure to passive smoking during pregnancy, 25(OH)D concentrations showed an inverse association with the risk of acquiring acute nasopharyngitis by 6 months of age (P for trend=0.0004). Conclusion The results show that 89.9% of healthy newborns in Korea are born with vitamin D insufficiency or deficiency (55.6% and 34.3%, respectively). Cord blood vitamin D insufficiency or deficiency in healthy neonates is associated with an increased risk of acute nasopharyngitis by 6 months of age. More time spent outdoors and more intensified vitamin D supplementation for pregnant women may be needed to prevent the onset of acute nasopharyngitis in infants. PMID:24244212

  15. The Association between Maternal 25-Hydroxyvitamin D Concentration during Gestation and Early Childhood Cardio-metabolic Outcomes: Is There Interaction with Pre-Pregnancy BMI?

    PubMed Central

    Hrudey, E. Jessica; Reynolds, Rebecca M.; Oostvogels, Adriëtte J. J. M.; Brouwer, Ingeborg A.; Vrijkotte, Tanja G. M.

    2015-01-01

    Both maternal 25-hydroxyvitamin D(25OHD) status and pre-pregnancy BMI(pBMI) may influence offspring cardio-metabolic outcomes. Lower 25OHD concentrations have been observed in women with both low and high pBMIs, but the combined influence of pBMI and 25OHD on offspring cardio-metabolic outcomes is unknown. Therefore, this study investigated the role of pBMI in the association between maternal 25OHD concentration and cardio-metabolic outcomes in 5-6 year old children. Data were obtained from the ABCD cohort study and 1882 mother-child pairs were included. The offspring outcomes investigated were systolic and diastolic blood pressure, heart rate, BMI, body fat percentage(%BF), waist-to-height ratio, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, glucose, C-peptide, and insulin resistance(HOMA2-IR). 62% of the C-peptide samples were below the detection limit and were thus imputed using survival analysis. Models were corrected for maternal and offspring covariates and tested for interaction with pBMI. Interaction with pBMI was observed in the associations with insulin resistance markers: in offspring of overweight mothers(≥25.0kg/m2), a 10 nmol/L increase in maternal 25OHD was associated with a 0.007(99%CI:-0.01,-0.001) nmol/L decrease in C-peptide and a 0.02(99%CI:-0.03,-0.004) decrease in HOMA2-IR. When only non-imputed data were analyzed, there was a trend for interaction in the relationship but the results lost significance. Interaction with pBMI was not observed for the other outcomes. A 10 nmol/L increase in maternal 25OHD was significantly associated with a 0.13%(99%CI:-0.3,-0.003) decrease in %BF after correction for maternal and child covariates. Thus, intrauterine exposure to both low 25OHD and maternal overweight may be associated with increased insulin resistance in offspring, while exposure to low 25OHD in utero may be associated with increased offspring %BF with no interactive effects from pBMI. Due to the limitations of this study

  16. The cutaneous photosynthesis of previtamin D3: a unique photoendocrine system

    SciTech Connect

    Holick, M.F.

    1981-07-01

    The skin has been recognized as the site for the sun-mediated photosynthesis of vitamin D3; until recently, however, very little was known about either the sequence of events leading to the formation of vitamin D3 in human skin or the factors that regulate the synthesis of this hormone. It is now established that, during exposure to sunlight, the cutaneous reservoir of 7-dehydrocholesterol (principally in the stratum Malpighii) converts to previtamin D3. Once this thermally labile previtamin is formed, it undergoes a temperature-dependent isomerization to vitamin D3 over a period of 3 days. The plasma vitamin-D binding protein preferentially translocates vitamin D3 from the skin into the circulation. During prolonged exposure to the sun, the accumulation of previtamin D3 is limited to about 10 to 15% of the original 7-dehydrocholesterol content because the previtamin photoisomerizes to 2 biologically inert photoproducts, lumisterol3 and tachysterol3. Increases in either latitude or the melanin concentration in the skin diminish the epidermal synthesis of previtamin D3. A single total body exposure to 3 minimal erythemal doses of ultraviolet radiation increased the vitamin-D3 levels in the serum 25-hydroxyvitamin-D levels after 7 days. The unique mechanism for the cutaneous synthesis, storage, and steady release of vitamin D3 into the circulation prompted an investigation into the potential therapeutic benefits of using the skin as the site for the synthesis and absorption of vitamin-D3 metabolites.

  17. Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with autism spectrum disorder.

    PubMed

    Coşkun, Salih; Şimşek, Şeref; Camkurt, Mehmet Akif; Çim, Abdullah; Çelik, Sercan Bulut

    2016-08-22

    Vitamin D is implicated in several aspects of human physiology, and polymorphisms in the vitamin D receptor gene (VDR) are associated with a variety of neuropsychiatric disorders. The aims of this study are to determine whether VDR polymorphisms are associated with autism spectrum disorder (ASD), to examine serum 25-hydroxyvitamin D (25(OH)D) levels in ASD, and to explore whether VDR polymorphisms influence serum 25(OH)D levels. We investigated 480 subjects (237 children with ASD and 243 healthy controls) for the following VDR polymorphisms: TaqI, BsmI, FokI, ApaI, and Cdx2.Within the same samples, 25(OH)D levels were available only for 85 patients and 82 controls. The Cdx-2 variation was shown to deviate from Hardy-Weinberg equilibrium in the controls and was therefore excluded from the study. We found that the frequency of rare FokI TT, TaqI CC, and BsmI AA genotypes differed significantly between children with ASD and the controls (p=0.042, p=0.016, p=0.038, respectively). After correction for multiple testing, only the TaqI CC genotype remained significant. Further analysis using a recessive model showed that rare genotypes of these polymorphisms were significantly higher in patients compared to controls (p=0.045, p=0.005 and p=0.031, respectively). However, no significant association was found between ApaI and ASD. We found serum 25(OH)D levels to be significantly higher in children with ASD (p<0.001) and that the FokI polymorphism had an effect on serum 25(OH)D levels in children with ASD (p=0.041). Additionally, we found the haplotype GTTT (BsmI/TaqI/FokI/ApaI) conferred an increased risk for developing ASD (p=0.022; odds ratio [95% confidence interval]=2.322 [1.105-4.879]). This is the first clinical study evaluating the association between serum 25(OH)D levels and VDR polymorphisms in children with ASD. Our results demonstrated a significant association between TaqI, BsmI, and FokI polymorphisms and ASD and showed for the first time that FokI polymorphisms

  18. Suntanning and cutaneous synthesis of vitamin D3.

    PubMed

    Matsuoka, L Y; Wortsman, J; Hollis, B W

    1990-07-01

    Skin tanning is the melanization of the epidermis induced by excessive sunlight exposure. Since melanin absorbs preferentially the wavelengths around 300 nm and the cutaneous synthesis of vitamin D3 is stimulated by the same wavelengths (290 to 320 nm, ultraviolet light B [UVB]), we investigated the effect of tanning on vitamin D3 formation. Vitamin D3 and 25 hydroxyvitamin D (25-OH-D) serum levels were measured during midwinter (untanned state) in seven healthy subjects. Blood was obtained immediately before whole body exposure to UVB in a phototherapy unit, and again 24 hours later. The study was repeated in the same subjects during midsummer (tanned state) using the same UVB dose. Serum vitamin D3 increased in the untanned state from 1.7 +/- 0.4 ng/ml (mean +/- SE) to 11 +/- 1.5 ng/ml following UVB (p less than 0.001). In the tanned state, basal serum vitamin D3 was significantly higher: 9.6 +/- 2.8 ng/ml (p less than 0.04 basal untanned versus basal tanned), and exhibited minimal rise after UVB to 14.3 +/- 4.1 ng/ml (p greater than 0.1 for tanned basal versus post UVB tanned). Tanning was also associated with significantly higher serum 25-OH-D levels: 22.5 +/- 2.9 ng/ml (untanned) versus 36.9 +/- 4.7 ng/ml (tanned) (p less than 0.02). Thus excessive solar exposure produces, besides erythema and tanning, the resetting of the vitamin D3 synthetic mechanism with blunting of the response to UVB.

  19. Photoaffinity labeling of human serum vitamin D binding protein and chemical cleavage of the labeled protein: Identification of an 11. 5-kDa peptide containing the putative 25-hydroxyvitamin D sub 3 binding site

    SciTech Connect

    Ray, R.; Holick, M.F. ); Bouillon, R.; Baelen, H.V. )

    1991-07-30

    In this paper, the authors describe photoaffinity labeling and related studies of human serum vitamin D binding protein (hDBP) with 25-hydroxyvitamin D{sub 3} 3{beta}-3{prime}-(N-(4-azido-2-nitrophenyl)amino)propyl ether (25-ANE) and its radiolabeled counterpart, i.e., 25-hydroxyvitamin D{sub 3} 3{beta}-3{prime}-(N-(4-azido-2-nitro-(3,5-{sup 3}H)phenyl)amino)propyl ether ({sup 3}H-25-ANE). They have carried out studies to demonstrate that (1) 25-ANE competes with 25-OH-D{sub 3} for the binding site of the latter in hDBP and (2) {sup 3}H-25-ANE is capable of covalently labeling the hDBP molecule when exposed ot UV light. Treatment of a sample of purified hDBP, labeled with {sup 3}H-25-ANE, with BNPS-skatole produced two Coomassie Blue stained peptide fragments, and the majority of the radioactivity was assoicated with the smaller of the two peptide fragments (16.5 kDa). On the other hand, cleavage of the labeled protein with cyanogen bromide produced a peptide (11.5 kDa) containing most of the covalently attached radioactivity. Considering the primary amino acid structure of hDBP, this peptide fragment (11.5 kDa) represents the N-terminus through residue 108 of the intact protein. Thus, the results tentatively identify this segment of the protein containing the binding pocket for 25-OH-D{sub 3}.

  20. Occurrence of Vitamin 25(OH)D3 Insufficiency in Young Women with Metabolic Syndrome

    PubMed Central

    Rogal, Karolina; Mankowska, Aneta

    2011-01-01

    Vitamin D insufficiency is prevalent and may be associated with higher risk for metabolic syndrome. Low serum 25-hydroxyvitamin D3 is known to perturb cellular function in many tissues, including the endocrine pancreas, which are involved in the pathogenesis of obesity and type 2 diabetes. This study examined the vitamin 25(OH)D3 concentration and its relationship with the metabolic syndrome among 52 young women aged 20-40 yrs with overweight and obese. As defined by revised International Diabetes Federation (IDF 2005) criteria, 27 of the 52 women had the metabolic syndrome (52%). Women with MS had significantly lower mean concentration of vitamin 25(OH)D3. Vitamin D insufficiency was more prevalent in women with MS, compared with those who did not fulfill the criteria for this syndrome (63% vs 37%, respectively) as well as among women with metabolic syndrome mild deficiency occurred much more frequently than in without MS (58% vs 26%, respectively). When serum concentrations of 25(OH)D3 were categorized in tertiles, there was a decreasing prevalence of MS in women with increasing concentrations of 25(OH)D3. The study findings suggest that insufficiency of vitamin 25(OH)D3 is more common in women with excessive body weight and metabolic syndrome than in women with excessive body weight without metabolic syndrome.

  1. Diminished internalization and action of 1,25-dihydroxyvitamin D3 in dermal fibroblasts cultured from New World primates

    SciTech Connect

    Adams, J.S.; Gacad, M.A.; Baker, A.J.; Kheun, G.; Rude, R.K.

    1985-06-01

    We investigated the occurrence of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3)-resistant osteomalacia in the New World primate colony of Saguinus imperator at the Los Angeles Zoo. The mean serum concentration of 1,25-(OH)2D3 was elevated 5-fold in the New World primates compared to that in their Old World counterparts. The specific internalization of 0.6 nM (/sup 3/H)1,25-(OH)2D3 by cultured dermal fibroblasts from New World primates was reduced 75% compared to that by cells from Old World primates or man. The decrease in hormone uptake resulted from a decrease in the number of high affinity intracellular binding sites for 1,25-(OH)2D3 and apparently caused a 90-95% reduction in 1,25-(OH)2D3-induced 25-hydroxyvitamin-D3-24-hydroxylase activity. There was no alteration in the capacity or avidity of New World primate serum for 1,25-(OH)2D3 compared to that of serum from Old World primates. These data suggest that the occurrence of vitamin D-resistant osteomalacia in New World primates is the result of decreased high affinity, receptor-mediated uptake of 1,25-(OH)2D3 by the target cell.

  2. The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism

    PubMed Central

    Slominski, Andrzej; Semak, Igor; Zjawiony, Jordan; Wortsman, Jacobo; Li, Wei; Szczesniewski, Andre; Tuckey, Robert C.

    2008-01-01

    We show that cytochrome P450scc (CYP11A1) in either a reconstituted system or in isolated adrenal mitochondria can metabolize vitamin D3. The major products of the reaction with reconstituted enzyme were 20-hydroxycholecalciferol and 20,22-dihydroxycholecalciferol, with yields of 16 and 4%, respectively, of the original vitamin D3 substrate. Trihydroxycholecalciferol was a minor product, likely arising from further metabolism of dihydroxycholecalciferol. Based on NMR analysis and known properties of P450scc we propose that hydroxylation of vitamin D3 by P450scc occurs sequentially and stereospecifically with initial formation of 20(S)-hydroxyvitamin D3. P450scc did not metabolize 25-hydroxyvitamin D3, indicating that modification of C25 protected it against P450scc action. Adrenal mitochondria also metabolized vitamin D3 yielding 10 hydroxyderivatives, with UV spectra typical of vitamin D triene chromophores. Aminogluthimide inhibition showed that the three major metabolites, but not the others, resulted from P450scc action. It therefore appears that non-P450scc enzymes present in the adrenal cortex to some extent contribute to metabolism of vitamin D3. We conclude that purified P450scc in a reconstituted system or P450scc in adrenal mitochondria can add one hydroxyl group to vitamin D3 with subsequent hydroxylation being observed for reconstituted enzyme but not for adrenal mitochondria. Additional vitamin D3 metabolites arise from the action of other enzymes in adrenal mitochondria. These findings appear to define novel metabolic pathways involving vitamin D3 that remain to be characterized. PMID:16098191

  3. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats.

    PubMed

    Boyan, Barbara D; Hyzy, Sharon L; Pan, Qingfen; Scott, Kayla M; Coutts, Richard D; Healey, Robert; Schwartz, Zvi

    2016-01-01

    Osteoarthritis (OA) in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OH)D3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] accumulates in articular cartilage following injection of [3H]-25(OH)D3. Previously, we showed that 24R,25(OH)2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH)2D3 in maintaining cartilage health. We examined the ability of 24R,25(OH)2D3 to prevent degenerative changes in articular cartilage in an OA-like environment and the potential mechanisms involved. In vitro, rat articular chondrocytes were treated with IL-1β with and without 24R,25(OH)2D3 or 1α,25(OH)2D3. 24R,25(OH)2D3 but not 1α,25(OH)2D3 blocked the effects of IL-1β in a dose-dependent manner, and its effect was partially mediated through the TGF-β1 signaling pathway. In vivo, unilateral anterior cruciate ligament transections were performed in immunocompetent rats followed by intra-articular injections of 24R,25(OH)2D3 or vehicle (t = 0, 7, 14, 21 days). Tissues were harvested on day 28. Joints treated with vehicle had changes typical of OA whereas joints treated with 24R,25(OH)2D3 had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH)2D3 protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis. PMID:27575371

  4. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats

    PubMed Central

    Boyan, Barbara D.; Hyzy, Sharon L.; Pan, Qingfen; Scott, Kayla M.; Coutts, Richard D.; Healey, Robert; Schwartz, Zvi

    2016-01-01

    Osteoarthritis (OA) in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OH)D3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] accumulates in articular cartilage following injection of [3H]-25(OH)D3. Previously, we showed that 24R,25(OH)2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH)2D3 in maintaining cartilage health. We examined the ability of 24R,25(OH)2D3 to prevent degenerative changes in articular cartilage in an OA-like environment and the potential mechanisms involved. In vitro, rat articular chondrocytes were treated with IL-1β with and without 24R,25(OH)2D3 or 1α,25(OH)2D3. 24R,25(OH)2D3 but not 1α,25(OH)2D3 blocked the effects of IL-1β in a dose-dependent manner, and its effect was partially mediated through the TGF-β1 signaling pathway. In vivo, unilateral anterior cruciate ligament transections were performed in immunocompetent rats followed by intra-articular injections of 24R,25(OH)2D3 or vehicle (t = 0, 7, 14, 21 days). Tissues were harvested on day 28. Joints treated with vehicle had changes typical of OA whereas joints treated with 24R,25(OH)2D3 had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH)2D3 protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis. PMID:27575371

  5. Vitamin D Intake and Serum 25-Hydroxyvitamin D Levels in Korean Adults: Analysis of the 2009 Korea National Health and Nutrition Examination Survey (KNHANES IV-3) Using a Newly Established Vitamin D Database

    PubMed Central

    Yoo, Kyoungok; Cho, Jinah; Ly, Sunyung

    2016-01-01

    Vitamin D is important for maintaining bone health and may prevent various diseases (i.e., cardiovascular disease and cancer). The aim of this study was to estimate vitamin D intakes of Korean adults using the Korea National Health and Nutrition Examination Survey (KNHANES, 2009) data and a newly established vitamin D database. KNHANES (2009) participants (n = 4541; 2021 men; 2520 women) aged ≥20 years were included. Dietary vitamin D intake, serum 25-hydroxyvitamin D (25(OH)D), and the relationship between vitamin D intake and serum 25(OH)D were evaluated. In men and women, vitamin D intakes were 4.00 ± 0.17 µg/day and 2.6 ± 0.1 µg/day respectively, and serum 25(OH)D concentrations were 19.78 ± 0.33 ng/mL and 17.10 ± 0.26 ng/mL respectively. Serum 25(OH)D concentrations of men aged <50 years and women aged >20 years were under 20 ng/mL. After adjusting for confounding factors, the positive relationship between vitamin D intake and serum 25(OH)D was observed in total subjects (p < 0.05), excluding participants ≥50 years old. The main food sources for vitamin D among Korean adults were fish/shellfish (71.34%) and egg (14.89%). Korean adults should increase their serum 25(OH)D concentrations by increasing vitamin D intake. PMID:27690097

  6. Assessing the relationship between vitamin D3 and stratum corneum hydration for the treatment of xerotic skin.

    PubMed

    Russell, Meghan

    2012-09-01

    Vitamin D(3) has been called the "sunshine" vitamin since the formation of vitamin D is mediated by exposure to sunlight. Vitamin D(3) is linked to many health benefits, however serum levels of vitamin D(3) have been decreasing over the last few decades and the lower levels of vitamin D(3) may have consequences on normal physiology. We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and stratum corneum conductance as well as the effect of topical application of cholecalciferol (vitamin D(3)) on dry skin. Eighty three subjects were recruited and blood serum levels and skin conductance measurements were taken after a one week washout. A correlation was observed between vitamin D levels and skin moisture content, individuals with lower levels of vitamin D had lower average skin moisture. Subsequently, a 3-week split leg, randomized, vehicle controlled clinical study was conducted on a subset of 61 of the above individuals who were identified with non-sufficient vitamin D serum levels. Topical supplementation with cholecalciferol significantly increased measurements of skin moisturization and resulted in improvements in subjective clinical grading of dry skin. Taken together our finding suggest a relationship between serum vitamin D(3) (25(OH)D) levels and hydration of the stratum corneum and further demonstrate the skin moisture benefit from topical application of vitamin D(3).

  7. Histone Deacetylation Mediates the Rejuvenation of Osteoblastogenesis by the Combination of 25(OH)D3 and Parathyroid Hormone in MSCs from Elders

    PubMed Central

    Zhou, Shuanhu; Geng, Shuo; Glowacki, Julie

    2012-01-01

    Vitamin D metabolites are important effectors of bone and mineral homeostasis. Human bone marrow stromal cells (hMSCs) are targets of 1α,25-dihydroxyvitamin D [1α, 25(OH)2D] action to promote their differentiation to osteoblasts. Osteoblastogenesis is also stimulated by 25-hydroxyvitamin D [25(OH)D], an effect that requires conversion to 1α, 25(OH)2D3 by 25-hydroxyvitamin D3 1α-hydroxylase (CYP27B1). These findings support an autocrine/paracrine role of vitamin D metabolism in osteoblastogenesis of hMSCs. In this study, we assessed whether and by what mechanisms osteoblastogenesis could be rejuvenated with hMSCs from elders. First, knockdown studies with VDR-siRNA showed that both the pro-differentiation and anti-proliferative effects of 1α, 25(OH)2D3 required VDR. Second, 100 nM 25(OH)D3 (p<0.01 vs. control, ANOVA) and 100 nM PTH1-34 (p<0.05) significantly stimulated alkaline phosphatase activity (a measure of osteoblastogenesis), with a synergistic effect when combined (p<0.001). Scriptaid, an inhibitor of histone deacetylase, blocked the effect of 25(OH)D3 and PTH on osteoblastogenesis. Scriptaid alone downregulated VDR in hMSCs. These data demonstrate that histone deacetylation is required for the synergistic effect of 25(OH)D3 and PTH on osteoblastogenesis in hMSCs. Both VDR siRNA and Scriptaid dowregulated VDR mRNA and inhibited osteoblastogenesis. Thus, epigenetic regulation of the VDR may be central to rejuvenating osteoblastogenesis in hMSCs from elders. PMID:22982627

  8. Sequestration and microsomal C-25 hydroxylation of (/sup 3/H)-vitamin D3 by the rat liver

    SciTech Connect

    Gascon-Barre, M.; Elbaz, H.; Therrien-Ferland, D.

    1985-03-01

    A study of the vitamin D3 (D3) 25-hydroxylase was undertaken in an in vivo-in vitro model. (/sup 3/H)-D3 (0.7, 1.0, 10, or 100 nmol/100 g of body weight) was injected into the portal vein and the liver was excised 18 seconds later. The liver homogenate was then submitted to differential centrifugation and the amount of (/sup 3/H)-D3 incorporated in the subcellular fractions was evaluated. The microsomal fraction was also incubated in vitro and the appearance of (/sup 3/H)-25-hydroxyvitamin D3 (25(OH)D3) was determined by high performance liquid chromatography (HPLC). Results showed that the fractional liver (/sup 3/H)-D3 uptake varied between 37 percent and 48 percent of the dose injected. The intracellular distribution of (/sup 3/H)-D3 showed that most of the vitamin was incorporated into the microsomal fraction (45% to 50% of the intracellular (/sup 3/H)-D3) except at the highest dose of (/sup 3/H)-D3 where the cytosolic fraction contained the highest amount (56.4%) of the incorporated vitamin. Mathematical analysis of the intracellular (/sup 3/H)-D3 distribution showed that the microsomal fraction was the only subcellular fraction that was found to incorporate (/sup 3/H)-D3 in relation to the total liver uptake of the vitamin. The apparent Michaelis-Menten kinetics of the (/sup 3/H)-D3-25-hydroxylase showed that with substrate concentration of up to 88.5 nM, the apparent Km and Vmax were 28.2 nM and 25.8 fentomoles (fmol) X min-1 X mg microsomal pro-1, respectively, but the reaction lost considerable efficiency with higher substrate concentrations.

  9. Measurement of vitamin D3 metabolites in smelter workers exposed to lead and cadmium

    PubMed Central

    Chalkley, S. R.; Richmond, J.; Barltrop, D.

    1998-01-01

    OBJECTIVES: To investigate the effects of lead and cadmium on the metabolic pathway of vitamin D3. METHODS: Blood and urinary cadmium and urinary total proteins were measured in 59 smelter workers occupationally exposed to lead and cadmium. In 19 of these workers, the plasma vitamin D3 metabolites, (25-hydroxycholecalciferol (25 OHD3), 24R, 25-dihydroxycholecalciferol (24R,25(OH)2D3) and 1 alpha,25- dihydroxycholecalciferol (1 alpha, 25(OH)2D3)) were measured together with blood lead. Vitamin D3 metabolites were measured by radioimmunoassay, (RIA), lead and cadmium by atomic absorption spectrophotometry, and total proteins with a test kit. RESULTS: Ranges for plasma 25(OH)D3, 24R,25(OH)2D3 and 1 alpha,25(OH)2D3 were 1.0-51.9 ng/ml, 0.6-5.8 ng/ml, and 0.1-75.7 pg/ml, respectively. Ranges for blood lead were 1-3.7 mumol/l, (21-76 micrograms/dl), blood cadmium 6- 145 nmol/l, and urinary cadmium 3-161 nmol/l. Total proteins in random urine samples were 2.1-32.6 mg/dl. Concentrations of lead and cadmium in blood showed no correlation (correlation coefficient -0.265) but there was a highly significant correlation between blood and urinary cadmium. Concentrations for 24R,25(OH)2D3 were depressed below the normal range as blood and urinary cadmium increased, irrespective of lead concentrations. High cadmium concentrations were associated with decreased plasma 1 alpha,25(OH)2D3 when lead concentrations were < 1.9 mumol/l and with above normal plasma 1 alpha,25(OH)2D3 when lead concentrations were > 1.9 mumol/l, Kruskal-Wallis analysis of variance (K-W ANOVA) chi 2 = 10.3, p = 0.006. Plasma 25(OH)D3 was negatively correlated with both urinary total proteins and urinary cadmium, but showed no correlation with plasma 24R,25(OH)2D3, 1 alpha,25(OH)2D3, blood lead, or blood cadmium. CONCLUSION: Continuous long term exposure to cadmium may result in a state of equilibrium between blood and urinary cadmium. Cadmium concentrations in blood could be predicted from the cadmium

  10. Cdx-2 polymorphism in Vitamin D Receptor gene was associated with serum 25-hydroxyvitamin D levels, bone mineral density and fracture in middle-aged and elderly Chinese women.

    PubMed

    Ling, Yan; Lin, Huandong; Aleteng, Qiqige; Ma, Hui; Pan, Baishen; Gao, Jian; Gao, Xin

    2016-05-15

    The aim of the current study was to examine the relationship between Cdx-2 polymorphism in the promoter region of the VDR gene and serum 25-hydroxyvitamin D (25(OH)D) levels, bone mineral density (BMD) and fracture in Chinese population. This was a cross-sectional study, which included 738 individuals (428 women and 310 men) aged 45 years or older. In women, the association of Cdx-2 polymorphism with serum 25(OH)D levels was significant adjusting for age, BMI, estimated glomerular filtration rate, menopausal status and season of blood collection (P = 0.002). Cdx-2 polymorphism was associated with lumbar spine BMD adjusted for age, BMI, menopausal status and serum 25(OH)D in women (P = 0.005). But it was not associated with femoral neck BMD or total hip BMD in women. In women, Cdx-2 polymorphism was also associated with fracture adjusted for age, BMI, menopausal status, serum 25(OH)D and total hip BMD (P = 0.03). Carriers of AA and AG genotypes was associated with a higher odds of fracture compared with the carriers of GG genotype (OR = 2.14, 95% CI 1.04-4.42 and OR = 1.90, 95% CI 1.03-3.51). In men, Cdx-2 polymorphism was not associated with serum 25(OH)D levels, BMD or fracture. Our results indicate that the association of Cdx-2 polymorphism in the VDR gene with serum 25(OH)D levels, BMD and fracture may have sex differences. Cdx-2 polymorphism in the VDR gene may affect the serum 25(OH)D concentrations and the risk of osteoporosis and fracture in middle-aged and elderly Chinese women. PMID:26970179

  11. Genetic associations with 25-hydroxyvitamin D deficiency in HIV-1-infected youth: fine-mapping for the GC/DBP gene that encodes the vitamin D-binding protein.

    PubMed

    Porter, Travis R; Li, Xuelin; Stephensen, Charles B; Mulligan, Kathleen; Rutledge, Brandy; Flynn, Patricia M; Lujan-Zilbermann, Jorge; Hazra, Rohan; Wilson, Craig M; Havens, Peter L; Tang, Jianming

    2013-01-01

    Serum 25-hydroxyvitamin D [25(OH)D] is often deficient (<12 ng/ml) or insufficient (<20 ng/ml) in youth living with human immunodeficiency virus type 1 infection (YLH). Based on evidence from multiple genome-wide association studies, we hypothesized that genetic factors associated with 25(OH)D deficiency should be readily detectable in YLH even when controlling for other known factors, including use of the antiretroviral drug efavirenz (EFV). Genotyping by bi-directional sequencing targeted 15 single nucleotide polymorphisms (SNPs) at the GC/DBP locus, with a focus on coding and regulatory variants, as well as those repeatedly reported in the literature. Three intronic SNPs (rs222016, rs222020, and rs222029) in a conserved haplotype block had unequivocal association signals (false discovery rate ≤ 0.006). In particular, the minor allele G for rs222020 was highly unfavorable among 192 YLH (99 African-Americans and 93 others), as gauged by relatively low likelihood for 25(OH)D sufficiency at enrollment (odds ratio = 0.31, p = 9.0 × 10(-4)). In a reduced multivariable model, race, season, latitude, body mass index, exposure to EFV, and rs222020-G were independent factors that collectively accounted for 38% of variance in the log10-transformed 25(OH)D concentration (p < 0.0001). Interaction terms were evident for rs222020-G × season (p < 0.001), latitude × season (especially fall and winter; p < 0.01), and race × EFV use (p = 0.024). Overall, variance in serum 25(OH)D is substantially attributable to multiple factors, but the exact contribution of genetic and non-genetic factors can be obscured by partial overlaps and frequent interactions.

  12. Genetic associations with 25-hydroxyvitamin D deficiency in HIV-1-infected youth: fine-mapping for the GC/DBP gene that encodes the vitamin D-binding protein

    PubMed Central

    Porter, Travis R.; Li, Xuelin; Stephensen, Charles B.; Mulligan, Kathleen; Rutledge, Brandy; Flynn, Patricia M.; Lujan-Zilbermann, Jorge; Hazra, Rohan; Wilson, Craig M.; Havens, Peter L.; Tang, Jianming

    2013-01-01

    Serum 25-hydroxyvitamin D [25(OH)D] is often deficient (<12 ng/ml) or insufficient (<20 ng/ml) in youth living with human immunodeficiency virus type 1 infection (YLH). Based on evidence from multiple genome-wide association studies, we hypothesized that genetic factors associated with 25(OH)D deficiency should be readily detectable in YLH even when controlling for other known factors, including use of the antiretroviral drug efavirenz (EFV). Genotyping by bi-directional sequencing targeted 15 single nucleotide polymorphisms (SNPs) at the GC/DBP locus, with a focus on coding and regulatory variants, as well as those repeatedly reported in the literature. Three intronic SNPs (rs222016, rs222020, and rs222029) in a conserved haplotype block had unequivocal association signals (false discovery rate ≤ 0.006). In particular, the minor allele G for rs222020 was highly unfavorable among 192 YLH (99 African–Americans and 93 others), as gauged by relatively low likelihood for 25(OH)D sufficiency at enrollment (odds ratio = 0.31, p = 9.0 × 10-4). In a reduced multivariable model, race, season, latitude, body mass index, exposure to EFV, and rs222020-G were independent factors that collectively accounted for 38% of variance in the log10-transformed 25(OH)D concentration (p < 0.0001). Interaction terms were evident for rs222020-G × season (p < 0.001), latitude × season (especially fall and winter; p < 0.01), and race × EFV use (p = 0.024). Overall, variance in serum 25(OH)D is substantially attributable to multiple factors, but the exact contribution of genetic and non-genetic factors can be obscured by partial overlaps and frequent interactions. PMID:24294218

  13. Vitamin D2 is much less effective than vitamin D3 in humans.

    PubMed

    Armas, Laura A G; Hollis, Bruce W; Heaney, Robert P

    2004-11-01

    Vitamins D(2) and D(3) are generally considered to be equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitamin D(2)) available in the U.S. market. The relative potencies of vitamins D(2) and D(3) were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the time course of serum vitamin D and 25-hydroxyvitamin D (25OHD) over a period of 28 d and measuring the area under the curve of the rise in 25OHD above baseline. The two calciferols produced similar rises in serum concentration of the administered vitamin, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60.2 ng.d/ml (150.5 nmol.d/liter) for vitamin D(2) and 204.7 (511.8) for vitamin D(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1. Vitamin D(2) potency is less than one third that of vitamin D(3). Physicians resorting to use of vitamin D(2) should be aware of its markedly lower potency and shorter duration of action relative to vitamin D(3).

  14. Effect of weekly high-dose vitamin D3 supplementation on serum cholecalciferol concentrations in pregnant women.

    PubMed

    Dimitris, Michelle C; Perumal, Nandita; Craig-Barnes, Hayley A; Leadley, Michael; Mahmud, Abdullah A; Baqui, Abdullah H; Roth, Daniel E

    2016-04-01

    Vitamin D status is conventionally defined by the serum concentration of 25-hydroxyvitamin D. However, it has been proposed that the serum cholecalciferol concentration (D3) also determines functional vitamin D sufficiency. The objective of this study was to describe the effect of weekly high-dose vitamin D3 supplementation on inter-dose serum D3 in pregnant women. We conducted a sub-study of a completed randomized double-blind placebo-controlled trial of vitamin D3 (35,000 IU/week) supplementation in late pregnancy (AViDD trial) in Dhaka, Bangladesh. This study included pregnant women enrolled at 26-29 weeks gestation who fully adhered to the prenatal supplement intervention for ≥8 consecutive weeks and for whom serum samples were available for D3 analysis (n=65). Serum D3 was uniformly low at enrolment. Mean D3 increased and was maximal at 1 day after vitamin D dose administration (152.09nmol/L, SD 25.11nmol/L) and remained significantly higher in VitD vs. Pl at 7 days (29.59nmol/L vs. 1.92nmol/L, p=0.007). Daily average of the group mean D3 during the week following dosing was 66.97nmol/L in VitD versus 2.13nmol/L in Pl. In conclusion, serum D3 remained significantly elevated throughout the week following ≥8 consecutive weekly doses of 35,000 IU D3 in pregnant women. However, the clinically significant minimum threshold of serum D3 remains to be established.

  15. Structural evidence for enhancement of sequential vitamin D3 hydroxylation activities by directed evolution of cytochrome P450 vitamin D3 hydroxylase.

    PubMed

    Yasutake, Yoshiaki; Fujii, Yoshikazu; Nishioka, Taiki; Cheon, Woo-Kwang; Arisawa, Akira; Tamura, Tomohiro

    2010-10-01

    Vitamin D(3) hydroxylase (Vdh) isolated from actinomycete Pseudonocardia autotrophica is a cytochrome P450 (CYP) responsible for the biocatalytic conversion of vitamin D(3) (VD(3)) to 1α,25-dihydroxyvitamin D(3) (1α,25(OH)(2)VD(3)) by P. autotrophica. Although its biological function is unclear, Vdh is capable of catalyzing the two-step hydroxylation of VD(3), i.e. the conversion of VD(3) to 25-hydroxyvitamin D(3) (25(OH)VD(3)) and then of 25(OH)VD(3) to 1α,25(OH)(2)VD(3), a hormonal form of VD(3). Here we describe the crystal structures of wild-type Vdh (Vdh-WT) in the substrate-free form and of the highly active quadruple mutant (Vdh-K1) generated by directed evolution in the substrate-free, VD(3)-bound, and 25(OH)VD(3)-bound forms. Vdh-WT exhibits an open conformation with the distal heme pocket exposed to the solvent both in the presence and absence of a substrate, whereas Vdh-K1 exhibits a closed conformation in both the substrate-free and substrate-bound forms. The results suggest that the conformational equilibrium was largely shifted toward the closed conformation by four amino acid substitutions scattered throughout the molecule. The substrate-bound structure of Vdh-K1 accommodates both VD(3) and 25(OH)VD(3) but in an anti-parallel orientation. The occurrence of the two secosteroid binding modes accounts for the regioselective sequential VD(3) hydroxylation activities. Moreover, these structures determined before and after directed evolution, together with biochemical and spectroscopic data, provide insights into how directed evolution has worked for significant enhancement of both the VD(3) 25-hydroxylase and 25(OH)VD(3) 1α-hydroxylase activities.

  16. 1α,25-Dihydroxyvitamin D3 Regulates Mitochondrial Oxygen Consumption and Dynamics in Human Skeletal Muscle Cells.

    PubMed

    Ryan, Zachary C; Craig, Theodore A; Folmes, Clifford D; Wang, Xuewei; Lanza, Ian R; Schaible, Niccole S; Salisbury, Jeffrey L; Nair, K Sreekumaran; Terzic, Andre; Sieck, Gary C; Kumar, Rajiv

    2016-01-15

    Muscle weakness and myopathy are observed in vitamin D deficiency and chronic renal failure, where concentrations of the active vitamin D3 metabolite, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), are low. To evaluate the mechanism of action of 1α,25(OH)2D3 in skeletal muscle, we examined mitochondrial oxygen consumption, dynamics, and biogenesis and changes in expression of nuclear genes encoding mitochondrial proteins in human skeletal muscle cells following treatment with 1α,25(OH)2D3. The mitochondrial oxygen consumption rate (OCR) increased in 1α,25(OH)2D3-treated cells. Vitamin D3 metabolites lacking a 1α-hydroxyl group (vitamin D3, 25-hydroxyvitamin D3, and 24R,25-dihydroxyvitamin D3) decreased or failed to increase OCR. 1α-Hydroxyvitamin D3 did not increase OCR. In 1α,25(OH)2D3-treated cells, mitochondrial volume and branching and expression of the pro-fusion protein OPA1 (optic atrophy 1) increased, whereas expression of the pro-fission proteins Fis1 (fission 1) and Drp1 (dynamin 1-like) decreased. Phosphorylated pyruvate dehydrogenase (PDH) (Ser-293) and PDH kinase 4 (PDK4) decreased in 1α,25(OH)2D3-treated cells. There was a trend to increased PDH activity in 1α,25(OH)2D3-treated cells (p = 0.09). 83 nuclear mRNAs encoding mitochondrial proteins were changed following 1α,25(OH)2D3 treatment; notably, PDK4 mRNA decreased, and PDP2 mRNA increased. MYC, MAPK13, and EPAS1 mRNAs, which encode proteins that regulate mitochondrial biogenesis, were increased following 1α,25(OH)2D3 treatment. Vitamin D receptor-dependent changes in the expression of 1947 mRNAs encoding proteins involved in muscle contraction, focal adhesion, integrin, JAK/STAT, MAPK, growth factor, and p53 signaling pathways were observed following 1α,25(OH)2D3 treatment. Five micro-RNAs were induced or repressed by 1α,25(OH)2D3. 1α,25(OH)2D3 regulates mitochondrial function, dynamics, and enzyme function, which are likely to influence muscle strength. PMID:26601949

  17. 1α,25-Dihydroxyvitamin D3 Regulates Mitochondrial Oxygen Consumption and Dynamics in Human Skeletal Muscle Cells.

    PubMed

    Ryan, Zachary C; Craig, Theodore A; Folmes, Clifford D; Wang, Xuewei; Lanza, Ian R; Schaible, Niccole S; Salisbury, Jeffrey L; Nair, K Sreekumaran; Terzic, Andre; Sieck, Gary C; Kumar, Rajiv

    2016-01-15

    Muscle weakness and myopathy are observed in vitamin D deficiency and chronic renal failure, where concentrations of the active vitamin D3 metabolite, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), are low. To evaluate the mechanism of action of 1α,25(OH)2D3 in skeletal muscle, we examined mitochondrial oxygen consumption, dynamics, and biogenesis and changes in expression of nuclear genes encoding mitochondrial proteins in human skeletal muscle cells following treatment with 1α,25(OH)2D3. The mitochondrial oxygen consumption rate (OCR) increased in 1α,25(OH)2D3-treated cells. Vitamin D3 metabolites lacking a 1α-hydroxyl group (vitamin D3, 25-hydroxyvitamin D3, and 24R,25-dihydroxyvitamin D3) decreased or failed to increase OCR. 1α-Hydroxyvitamin D3 did not increase OCR. In 1α,25(OH)2D3-treated cells, mitochondrial volume and branching and expression of the pro-fusion protein OPA1 (optic atrophy 1) increased, whereas expression of the pro-fission proteins Fis1 (fission 1) and Drp1 (dynamin 1-like) decreased. Phosphorylated pyruvate dehydrogenase (PDH) (Ser-293) and PDH kinase 4 (PDK4) decreased in 1α,25(OH)2D3-treated cells. There was a trend to increased PDH activity in 1α,25(OH)2D3-treated cells (p = 0.09). 83 nuclear mRNAs encoding mitochondrial proteins were changed following 1α,25(OH)2D3 treatment; notably, PDK4 mRNA decreased, and PDP2 mRNA increased. MYC, MAPK13, and EPAS1 mRNAs, which encode proteins that regulate mitochondrial biogenesis, were increased following 1α,25(OH)2D3 treatment. Vitamin D receptor-dependent changes in the expression of 1947 mRNAs encoding proteins involved in muscle contraction, focal adhesion, integrin, JAK/STAT, MAPK, growth factor, and p53 signaling pathways were observed following 1α,25(OH)2D3 treatment. Five micro-RNAs were induced or repressed by 1α,25(OH)2D3. 1α,25(OH)2D3 regulates mitochondrial function, dynamics, and enzyme function, which are likely to influence muscle strength.

  18. A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia.

    PubMed

    Zabul, Piotr; Wozniak, Michal; Slominski, Andrzej T; Preis, Krzysztof; Gorska, Magdalena; Korozan, Marek; Wieruszewski, Jan; Zmijewski, Michal A; Zabul, Ewa; Tuckey, Robert; Kuban-Jankowska, Alicja; Mickiewicz, Wieslawa; Knap, Narcyz

    2015-01-01

    A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F(2t)-isoprostane were significantly higher in preeclamptic patients relative to the control (3.05 vs. 2.00 ng/mg creatinine). Surprisingly enough, plasma levels of 25-hydroxyvitamin D3 in both study groups were below the clinical reference range with no significant difference between the groups. In vitro study performed on isolated placental mitochondria and placental cell line showed that suicidal self-oxidation of cytochrome P450scc may lead to structural disintegration of heme, potentially contributing to enhancement of oxidative stress phenomena in the course of preeclampsia. As placental cytochrome P450scc pleiotropic activity is implicated in the metabolism of free radical mediated arachidonic acid derivatives as well as multiple Vitamin D3 hydroxylations and progesterone synthesis, we propose that Vitamin D3 might act as a competitive inhibitor of placental cytochrome P450scc preventing the production of lipid peroxides or excess progesterone synthesis, both of which may contribute to the etiopathogenesis of preeclampsia. The proposed molecular mechanism is in accord with the preliminary clinical observations on the surprisingly high efficacy of high-dose Vitamin D3 supplementation in prevention and treatment of preeclampsia. PMID:26068234

  19. A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia

    PubMed Central

    Zabul, Piotr; Wozniak, Michal; Slominski, Andrzej T.; Preis, Krzysztof; Gorska, Magdalena; Korozan, Marek; Wieruszewski, Jan; Zmijewski, Michal A.; Zabul, Ewa; Tuckey, Robert; Kuban-Jankowska, Alicja; Mickiewicz, Wieslawa; Knap, Narcyz

    2015-01-01

    A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F2t-isoprostane were significantly higher in preeclamptic patients relative to the control (3.05 vs. 2.00 ng/mg creatinine). Surprisingly enough, plasma levels of 25-hydroxyvitamin D3 in both study groups were below the clinical reference range with no significant difference between the groups. In vitro study performed on isolated placental mitochondria and placental cell line showed that suicidal self-oxidation of cytochrome P450scc may lead to structural disintegration of heme, potentially contributing to enhancement of oxidative stress phenomena in the course of preeclampsia. As placental cytochrome P450scc pleiotropic activity is implicated in the metabolism of free radical mediated arachidonic acid derivatives as well as multiple Vitamin D3 hydroxylations and progesterone synthesis, we propose that Vitamin D3 might act as a competitive inhibitor of placental cytochrome P450scc preventing the production of lipid peroxides or excess progesterone synthesis, both of which may contribute to the etiopathogenesis of preeclampsia. The proposed molecular mechanism is in accord with the preliminary clinical observations on the surprisingly high efficacy of high-dose Vitamin D3 supplementation in prevention and treatment of preeclampsia. PMID:26068234

  20. A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia.

    PubMed

    Zabul, Piotr; Wozniak, Michal; Slominski, Andrzej T; Preis, Krzysztof; Gorska, Magdalena; Korozan, Marek; Wieruszewski, Jan; Zmijewski, Michal A; Zabul, Ewa; Tuckey, Robert; Kuban-Jankowska, Alicja; Mickiewicz, Wieslawa; Knap, Narcyz

    2015-06-09

    A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F(2t)-isoprostane were significantly higher in preeclamptic patients relative to the control (3.05 vs. 2.00 ng/mg creatinine). Surprisingly enough, plasma levels of 25-hydroxyvitamin D3 in both study groups were below the clinical reference range with no significant difference between the groups. In vitro study performed on isolated placental mitochondria and placental cell line showed that suicidal self-oxidation of cytochrome P450scc may lead to structural disintegration of heme, potentially contributing to enhancement of oxidative stress phenomena in the course of preeclampsia. As placental cytochrome P450scc pleiotropic activity is implicated in the metabolism of free radical mediated arachidonic acid derivatives as well as multiple Vitamin D3 hydroxylations and progesterone synthesis, we propose that Vitamin D3 might act as a competitive inhibitor of placental cytochrome P450scc preventing the production of lipid peroxides or excess progesterone synthesis, both of which may contribute to the etiopathogenesis of preeclampsia. The proposed molecular mechanism is in accord with the preliminary clinical observations on the surprisingly high efficacy of high-dose Vitamin D3 supplementation in prevention and treatment of preeclampsia.

  1. Optimal vitamin D3 daily intake of 2000IU inferred from modeled solar exposure of ancestral humans in Northern Tanzania.

    PubMed

    Krzyścin, Janusz W; Guzikowski, Jakub; Rajewska-Więch, Bonawentura

    2016-06-01

    Recently, high serum 25-hydroxyvitamin D concentration (~110nmol/L) was found in the Hadza tribe still keeping ancient hunter-gather life style. This level could serve as optimal vitamin D level that was built during millennia of human evolution. The personal vitamin D3 effective solar exposures of the Hadza adults are estimated using radiative model simulations with input from the satellite observations over lake Eyasi (3.7°S, 35.0°E). The calculations are carried out assuming the Hadza typical clothing habits and specific scenarios of the out-door activity comprising early morning and late afternoon working time in sun and prolonged midday siesta in the shade. The modeled doses received by the Hadza are converted to the vitamin D3 effective daily doses pertaining to the lighter skinned persons. We propose a novel formula to get adequate vitamin D level - exposure of 1/3 MED around local noon to 1/3 part of the whole body during warm sub-period of the year in the low- and mid-latitude regions. Such daily solar exposure is equivalent to ~2000IU of vitamin D3 taken orally. For many contemporary humans with limited out-door activity habit achieving such daily norm requires vitamin D3 supplementation of 2000IU throughout the whole year. PMID:27043260

  2. The efficacy of a vitamin D(3) metabolite for improving the myofibrillar tenderness of meat from Bos indicus cattle.

    PubMed

    Lawrence, R W; Doyle, J; Elliott, R; Loxton, I; McMeniman, J P; Norton, B W; Reid, D J; Tume, R W

    2006-01-01

    The influence of a once only administration of a metabolite of vitamin D(3) (HY·D(®)-25-hydroxy vitamin D(3)) on myofibrillar meat tenderness in Australian Brahman cattle was studied. Ninety-six Brahman steers of three phenotypes (Indo-Brazil, US and US/European) and with two previous hormonal growth promotant (HGP) histories (implanted or not implanted with Compudose(®)) were fed a standard feedlot ration for 70d. Treatment groups of 24 steers were offered daily 10g/head HY·D(®) (125mg 25-hydroxyvitamin D(3)) for 6, 4, or 2d before slaughter. One other group of 24 steers was given the basal diet without HY·D(®). Feed lot performance, blood and muscle samples and carcass quality data were collected at slaughter. Calcium, magnesium, potassium, sodium, iron and Vitamin D(3) metabolites were measured in plasma and longissimus dorsi muscle. Warner-Bratzler (WB) shear force (peak force, initial yield) and other objective meat quality measurements were made on the longissimus dorsi muscle of each steer after ageing for 1, 7 and 14d post-mortem at 0-2°C. There were no significant effects of HY·D(®) supplements on average daily gain (ADG, 1.28-1.45kg/d) over the experimental period. HY·D(®) supplements given 6d prior to slaughter resulted in significantly higher (P<0.05) initial yield values compared to supplements given 2d prior to slaughter. Supplementation had no significant effect on meat colour, ultimate pH, sarcomere length, cooking loss, instron compression or peak force. There was a significant treatment (HY·D(®)) by phenotype/HGP interaction for peak force (P=0.028), in which Indo-Brazil steers without previous HGP treatment responded positively (increased tenderness) to HY·D(®) supplements at 2d when compared with Indo-Brazil steers previously given HGP. There were no significant effects of treatment on other phenotypes. HY·D(®) supplements did not affect muscle or plasma concentrations of calcium, potassium or sodium, but did significantly

  3. The efficacy of a vitamin D(3) metabolite for improving the myofibrillar tenderness of meat from Bos indicus cattle.

    PubMed

    Lawrence, R W; Doyle, J; Elliott, R; Loxton, I; McMeniman, J P; Norton, B W; Reid, D J; Tume, R W

    2006-01-01

    The influence of a once only administration of a metabolite of vitamin D(3) (HY·D(®)-25-hydroxy vitamin D(3)) on myofibrillar meat tenderness in Australian Brahman cattle was studied. Ninety-six Brahman steers of three phenotypes (Indo-Brazil, US and US/European) and with two previous hormonal growth promotant (HGP) histories (implanted or not implanted with Compudose(®)) were fed a standard feedlot ration for 70d. Treatment groups of 24 steers were offered daily 10g/head HY·D(®) (125mg 25-hydroxyvitamin D(3)) for 6, 4, or 2d before slaughter. One other group of 24 steers was given the basal diet without HY·D(®). Feed lot performance, blood and muscle samples and carcass quality data were collected at slaughter. Calcium, magnesium, potassium, sodium, iron and Vitamin D(3) metabolites were measured in plasma and longissimus dorsi muscle. Warner-Bratzler (WB) shear force (peak force, initial yield) and other objective meat quality measurements were made on the longissimus dorsi muscle of each steer after ageing for 1, 7 and 14d post-mortem at 0-2°C. There were no significant effects of HY·D(®) supplements on average daily gain (ADG, 1.28-1.45kg/d) over the experimental period. HY·D(®) supplements given 6d prior to slaughter resulted in significantly higher (P<0.05) initial yield values compared to supplements given 2d prior to slaughter. Supplementation had no significant effect on meat colour, ultimate pH, sarcomere length, cooking loss, instron compression or peak force. There was a significant treatment (HY·D(®)) by phenotype/HGP interaction for peak force (P=0.028), in which Indo-Brazil steers without previous HGP treatment responded positively (increased tenderness) to HY·D(®) supplements at 2d when compared with Indo-Brazil steers previously given HGP. There were no significant effects of treatment on other phenotypes. HY·D(®) supplements did not affect muscle or plasma concentrations of calcium, potassium or sodium, but did significantly

  4. A protective role of dietary vitamin D3 in rat colon carcinogenesis.

    PubMed

    Mokady, E; Schwartz, B; Shany, S; Lamprecht, S A

    2000-01-01

    The aim of the present work was to gain insight into a putative anticancer effect of dietary vitamin D3 (cholecalciferol) in a rat model of colon carcinogenesis. Male rats were assigned to three different dietary groups. The dietary regimens were based on a standard murine-defined diet (AIN-76A) or a stress diet containing 20% fat, reduced Ca2+ concentration, a high phosphorus-to-Ca2+ ratio, and either low or high vitamin D3 content. Colorectal cancer was induced by administration of the procarcinogen 1,2-dimethylhydrazine (DMH). Blood Ca2+, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and 25-hydroxyvitamin D3 [25(OH)D3] levels were measured in DMH-treated rats and in respective weight- and age-matched dietary control groups. Colonic epithelial proliferation was assessed by determining thymidine kinase (TK) activity, bromodeoxyuridine (BrdUrd) incorporation into crypt cell DNA, and the mean labeling index along the colonic crypt continuum. Maintenance of rats on the stress diet either unmodified or supplemented with vitamin D3 in the absence of carcinogen treatment provoked a time-dependent rise in colonic TK activity and hyperproliferation of colonic epithelium. DMH treatment of rats maintained on the standard diet caused a marked increase in the proliferative indexes of colonic epithelium and in expansion of the crypt proliferative compartment. TK activity and the crypt mitotic zone were significantly augmented in the animal group fed the stress diet. Supplementary vitamin D3 abrogated the stress diet-enhanced colonic responses to the carcinogenic insult. Colon tumor multiplicity was fourfold higher in animals fed the stress diet than in animals maintained on a standard diet. The marked rise in colonic tumor multiplicity and adenocarcinoma incidence in rats fed the stress diet was obliterated by supplemental dietary vitamin D3. Cumulatively, the present results indicate that dietary vitamin D3 impedes the neoplastic process in murine large intestine and strengthen the

  5. Evaluating the clinical and physiological effects of long term ultraviolet B radiation on guinea pigs (Cavia porcellus).

    PubMed

    Watson, Megan K; Stern, Adam W; Labelle, Amber L; Joslyn, Stephen; Fan, Timothy M; Leister, Katie; Kohles, Micah; Marshall, Kemba; Mitchell, Mark A

    2014-01-01

    Vitamin D is an important hormone in vertebrates. Most animals acquire this hormone through their diet, secondary to exposure to ultraviolet B (UVB) radiation, or a combination thereof. The objectives for this research were to evaluate the clinical and physiologic effects of artificial UVB light supplementation on guinea pigs (Cavia porcellus) and to evaluate the long-term safety of artificial UVB light supplementation over the course of six months. Twelve juvenile acromelanic Hartley guinea pigs were randomly assigned to one of two treatment groups: Group A was exposed to 12 hours of artificial UVB radiation daily and Group B received only ambient fluorescent light for 12 hours daily. Animals in both groups were offered the same diet and housed under the same conditions. Blood samples were collected every three weeks to measure blood chemistry values, parathyroid hormone, ionized calcium, and serum 25-hydroxyvitamin D3 (25-OHD3) levels. Serial ophthalmologic examinations, computed tomography scans, and dual energy x-ray absorptiometry scans were performed during the course of the study. At the end of the study the animals were euthanized and necropsied. Mean ± SD serum 25-OHD3 concentrations differed significantly in the guinea pigs (p<0.0001) between the UVB supplementation group (101.49±21.81 nmol/L) and the control group (36.33±24.42 nmol/L). An increased corneal thickness in both eyes was also found in the UVB supplementation compared to the control group (right eye [OD]: p<0.0001; left eye [OS]: p<0.0001). There were no apparent negative clinical or pathologic side effects noted between the groups. This study found that exposing guinea pigs to UVB radiation long term significantly increased their circulating serum 25-OHD3 levels, and that this increase was sustainable over time. Providing guinea pigs exposure to UVB may be an important husbandry consideration that is not currently recommended. PMID:25517408

  6. Evaluating the Clinical and Physiological Effects of Long Term Ultraviolet B Radiation on Guinea Pigs (Cavia porcellus)

    PubMed Central

    Watson, Megan K.; Stern, Adam W.; Labelle, Amber L.; Joslyn, Stephen; Fan, Timothy M.; Leister, Katie; Kohles, Micah; Marshall, Kemba; Mitchell, Mark A.

    2014-01-01

    Vitamin D is an important hormone in vertebrates. Most animals acquire this hormone through their diet, secondary to exposure to ultraviolet B (UVB) radiation, or a combination thereof. The objectives for this research were to evaluate the clinical and physiologic effects of artificial UVB light supplementation on guinea pigs (Cavia porcellus) and to evaluate the long-term safety of artificial UVB light supplementation over the course of six months. Twelve juvenile acromelanic Hartley guinea pigs were randomly assigned to one of two treatment groups: Group A was exposed to 12 hours of artificial UVB radiation daily and Group B received only ambient fluorescent light for 12 hours daily. Animals in both groups were offered the same diet and housed under the same conditions. Blood samples were collected every three weeks to measure blood chemistry values, parathyroid hormone, ionized calcium, and serum 25-hydroxyvitamin D3 (25-OHD3) levels. Serial ophthalmologic examinations, computed tomography scans, and dual energy x-ray absorptiometry scans were performed during the course of the study. At the end of the study the animals were euthanized and necropsied. Mean ± SD serum 25-OHD3 concentrations differed significantly in the guinea pigs (p<0.0001) between the UVB supplementation group (101.49±21.81 nmol/L) and the control group (36.33±24.42 nmol/L). An increased corneal thickness in both eyes was also found in the UVB supplementation compared to the control group (right eye [OD]: p<0.0001; left eye [OS]: p<0.0001). There were no apparent negative clinical or pathologic side effects noted between the groups. This study found that exposing guinea pigs to UVB radiation long term significantly increased their circulating serum 25-OHD3 levels, and that this increase was sustainable over time. Providing guinea pigs exposure to UVB may be an important husbandry consideration that is not currently recommended. PMID:25517408

  7. An evaluation of the effects of added vitamin D3 in maternal diets on sow and pig performance.

    PubMed

    Flohr, J R; Tokach, M D; Dritz, S S; DeRouchey, J M; Goodband, R D; Nelssen, J L; Bergstrom, J R

    2014-02-01

    A total of 84 sows (PIC 1050) and their litters were used to determine the effects of supplementing maternal diet with vitamin D3 on sow and pig performance, serum 25-hydroxyvitamin D3 (25(OH)D3), milk vitamin D3, neonatal bone mineralization, and neonatal tissue vitamin D3. After breeding, sows were randomly assigned to 1 of 3 dietary vitamin D3 treatments (1,500, 3,000, or 6,000 IU/kg of complete diets). Sows were bled on d 0 and 100 of gestation and at farrowing and weaning (d 21). Pig BW was recorded at birth and weaning, and serum was collected from 2 pigs/litter at birth, on d 10 and at weaning. A total of 54 pigs (18/treatment) were euthanized at birth and necropsied to sample bones and tissues. Sow and suckling pig performance and neonatal bone ash and bone density did not differ among maternal vitamin D3 treatments; however, sow 25(OH)D3 and milk vitamin D3 increased (linear, P < 0.01) with increasing maternal vitamin D3 supplementation. Piglet serum 25(OH)D3 increased (quadratic, P < 0.03) with increased maternal vitamin D3. Neonatal kidney vitamin D3 tended (quadratic, P = 0.08) to decrease with increasing maternal vitamin D3, but liver vitamin D3 tended (linear, P = 0.09) to increase with increasing maternal vitamin D3. At weaning, a subsample of 180 pigs (PIC 327 × 1050) were used in a 3 × 2 split plot design for 35 d to determine the effects of maternal vitamin D3 and 2 levels of dietary vitamin D3 (1,800 or 18,000 IU/kg) from d 0 to 10 postweaning on nursery growth and serum 25(OH)D3. Overall (d 0 to 35), nursery ADG and G:F were not affected by either concentration of vitamin D3, but ADFI tended (quadratic, P < 0.06) to decrease with increasing maternal vitamin D3 as pigs from sows fed 3,000 IU had lower ADFI compared with pigs from sows fed 1,500 or 6,000 IU/kg. Nursery pig serum 25(OH)D3 increased with increasing maternal vitamin D3 (weaning) on d 0 (linear, P < 0.01), and maternal × diet interactions (P < 0.01) were observed on d 10 and 21

  8. 1,25(OH)2D3 Deficiency Induces Colon Inflammation via Secretion of Senescence-Associated Inflammatory Cytokines

    PubMed Central

    Zhi, Chunchun; Shen, Ming; Sun, Weiwei; Miao, Dengshun; Yuan, Xiaoqin

    2016-01-01

    Epidemiological studies showed that 1,25-Dihydroxyvitamin D[1,25(OH)2D3] insufficiency appears to be associated with aging and colon cancer while underlying biological mechanisms remain largely unknown. Inflammatory bowel disease is one of the risk factors for colon cancer. In this study, we investigated whether 1,25(OH)2D3 deficiency has an impact on the colon of 25-hydroxyvitamin D 1α-hydroxylase knockout [Cyp27b1−/−] mice fed on a rescue diet (high calcium, phosphate, and lactose) from weaning to 10 months of age. We found that 1,25(OH)2D3 deficient mice displayed significant colon inflammation phenotypes including shortened colon length, thinned and disordered mucosal structure, and inflammatory cell infiltration. DNA damage, cellular senescence and the production of senescence-associated inflammatory cytokines were also increased significantly in the colon of Cyp27b1−/−mice. Furthermore, the levels of ROS in the colon were increased significantly, whereas the expression levels of antioxidative genes were down-regulated dramatically in the colon of Cyp27b1−/−mice. Taken together, our results demonstrated that 1,25(OH)2D3 deficiency could induce colon inflammation, which may result from increased oxidative stress and DNA damage, subsequently, induced cell senescence and overproduction of senescence-associated secretory factors. Therefore, our findings suggest that 1,25(OH)2D3 may play an important role in preventing the development and progression of colon inflammation and colon cancer. PMID:26790152

  9. Gene Expression Profiles in Human and Mouse Primary Cells Provide New Insights into the Differential Actions of Vitamin D3 Metabolites

    PubMed Central

    Tuohimaa, Pentti; Wang, Jing-Huan; Khan, Sofia; Kuuslahti, Marianne; Qian, Kui; Manninen, Tommi; Auvinen, Petri; Vihinen, Mauno; Lou, Yan-Ru

    2013-01-01

    1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) had earlier been regarded as the only active hormone. The newly identified actions of 25-hydroxyvitamin D3 (25(OH)D3) and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) broadened the vitamin D3 endocrine system, however, the current data are fragmented and a systematic understanding is lacking. Here we performed the first systematic study of global gene expression to clarify their similarities and differences. Three metabolites at physiologically comparable levels were utilized to treat human and mouse fibroblasts prior to DNA microarray analyses. Human primary prostate stromal P29SN cells (hP29SN), which convert 25(OH)D3 into 1α,25(OH)2D3 by 1α-hydroxylase (encoded by the gene CYP27B1), displayed regulation of 164, 171, and 175 genes by treatment with 1α,25(OH)2D3, 25(OH)D3, and 24R,25(OH)2D3, respectively. Mouse primary Cyp27b1 knockout fibroblasts (mCyp27b1−/−), which lack 1α-hydroxylation, displayed regulation of 619, 469, and 66 genes using the same respective treatments. The number of shared genes regulated by two metabolites is much lower in hP29SN than in mCyp27b1−/−. By using DAVID Functional Annotation Bioinformatics Microarray Analysis tools and Ingenuity Pathways Analysis, we identified the agonistic regulation of calcium homeostasis and bone remodeling between 1α,25(OH)2D3 and 25(OH)D3 and unique non-classical actions of each metabolite in physiological and pathological processes, including cell cycle, keratinocyte differentiation, amyotrophic lateral sclerosis signaling, gene transcription, immunomodulation, epigenetics, cell differentiation, and membrane protein expression. In conclusion, there are three distinct vitamin D3 hormones with clearly different biological activities. This study presents a new conceptual insight into the vitamin D3 endocrine system, which may guide the strategic use of vitamin D3 in disease prevention and treatment. PMID:24116037

  10. The Impact of Vitamin D3 Supplementation on Muscle Function among HIV-Infected Children and Young Adults: A Randomized Controlled Trial

    PubMed Central

    Brown, Justin C.; Schall, Joan I.; Rutstein, Richard M.; Leonard, Mary B.; Zemel, Babette S.; Stallings, Virginia A.

    2015-01-01

    Objectives We tested the hypothesis that daily vitD3 supplementation increases neuromuscular motor skills, jump power, jump energy, muscular force, and muscular strength. Methods This was a secondary analysis of a randomized controlled trial of 12-months of oral 7,000 IU/day vitD3 supplementation or placebo among 56 persons living with HIV aged 9–25 years. Neuromuscular motor skills were quantified using the Bruininks-Oseretsky Test of Motor Proficiency. Power was quantified using peak jump power, and energy was quantified using peak jump height. Muscular force was quantified using isometric ankle plantar- and dorsiflexion, isokinetic knee flexion and extension. Muscular strength was quantified using isometric handgrip strength. Results After 12-months, serum 25-hydroxyvitamin D [25(OH)D] was higher with supplementation versus placebo (β=12.1 ng/mL; P<0.001). In intention-to-treat analyses, supplementation improved neuromuscular motor skills versus placebo (β=1.14; P=0.041). We observed no effect of supplementation on jump power, jump energy, muscular force, or muscular strength outcomes versus placebo. Conclusions Among HIV-infected children and young adults supplementation with daily high-dose vitD3 increased concentration of serum 25(OH)D and improved neuromuscular motor skills versus placebo. PMID:26032206

  11. Simultaneous determination of vitamins A and D3 in dairy products by liquid chromatography-tandem mass spectrometry (LC-MS/MS)

    NASA Astrophysics Data System (ADS)

    Barakat, I. S. A.; Hammouri, M. K.; Habib, I.

    2015-10-01

    A potential method for simultaneous determination of vitamin A and vitamin D3 (25- hydroxyvitamin D3) in fresh milk samples is addressed. The method is based on combination of high performance liquid chromatography and mass spectrometry during the course of analysis. The method applied for determination of vitamins A and D3 on eighteen (18) different fresh milk samples using liquid chromatography along with tandem -mass spectrometry. The work describes the suitability of the proposed method for the simultaneous determination of both vitamins using LC-MS/MS as a specific and quantitative technique. The vitamins of milk were separated by C18 Thermo gold column(100mm × 4.6mm × 5 μm) with a flow rate of 1ml/min (using an isocratic mobile phase). The method was validated using duplicate analyses, relative recovery experiment, and comparative analysis with control samples. Liquid- liquid extraction was employed as a pre-concentration step with n-hexane - dichloromethane mixture (90%:10%) as an extraction solvent. The molecular ions (m/z) appeared near 286 and 385nm and for the base peaks were appeared near 255 and 355nm for vitamins A and D3. Good correlation coefficients were obtained, 0.9999 for vitamin D3 and 0.9994 for vitamin A. The limit of detection and the limit of quantification were found to be 0.09ng/ml and 0.54ng/ml for vitamin D3 and 0.32ng/ml and 1.8ng/ml and for vitamin A. The proposed method showed excellent recoveries, about 98% for both vitamins A and D3.

  12. Differences in mineral metabolism among nonhuman primates receiving diets with only vitamin D3 or only vitamin D2.

    PubMed

    Marx, S J; Jones, G; Weinstein, R S; Chrousos, G P; Renquist, D M

    1989-12-01

    We tested for differences in aspects of mineral metabolism during the administration of diets with only vitamin D3 or only vitamin D2 in four nonhuman anthropoid primate species [two catarrhini, Macaca fascicularis (crab-eating macaque) and Macaca mulatta (rhesus macaque), and two platyrrhini, Saimiri sciureus (squirrel monkey) and Aotus vociferans (night monkey)]. All four species maintained approximately 2- to 3-fold higher serum 25-hydroxyvitamin D (25OHD) level while receiving vitamin D3 than while receiving similar amounts of vitamin D2. Serum 25OHD in M. mulatta receiving the standard primate dietary supplement of vitamin D3 was high enough (360 +/- 60 vs. 70 +/- 25 nM in vitamin D-supplemented humans; P less than 0.0001) to suggest that this widely used level of vitamin D3 supplementation is excessive for some M. mulatta. Serum 24,25-dihydroxyvitamin D [24,25-(OH)2D] in A. vociferans was uniquely high [P less than 0.01; species mean, 19 +/- 5, 95 +/- 12, and 27 +/- 5 nM in groups receiving diets with 1.5 IU vitamin D3/g, 6.6 IU vitamin D3/g, and 15 IU vitamin D2/g, respectively; mean 24,25-(OH)2D from the other three species pooled across three diets was 7 +/- 5 nM]. We confirmed relative resistance to 1,25-(OH)2D in S. sciureus, manifested by osteomalacia and moderately high serum 1,25-(OH)2D. Serum 1,25-(OH)2D in S. sciureus increased 4-fold (P less than 0.05) when the precursor in serum was changed from 250HD3 to 250HD2, suggesting that this species shows more severe resistance to 1,25-(OH)2D2 than to 1,25-(OH)2D3. In conclusion, we found many differences in vitamin D metabolism among four nonhuman anthropoid primate species. The striking feature in A. vociferans (high, 24,25-(OH)2D without high 25OHD in serum independent of whether diet contained only vitamin D3 or only vitamin D2) should allow determination of whether 24,25-(OH)2D functions as a unique agonist or an inactive metabolite in this species.

  13. Effect of dietary vitamin D3 (cholecalciferol) on colon carcinogenesis induced by 1,2-dimethylhydrazine in male Fischer 344 rats.

    PubMed

    Comer, P F; Clark, T D; Glauert, H P

    1993-01-01

    This study examined the effect of increasing dietary vitamin D on chemically induced colon carcinogenesis. Male Fischer 344 rats were first injected with 1,2-dimethylhydrazine (200 mg/kg) and then fed one of five dietary levels of vitamin D as cholecalciferol (250, 1,000, 2,000, 4,000, and 10,000 IU/kg diet) for nine months. Dietary vitamin D3 had no effect on weight gain. Plasma 25-hydroxyvitamin D3 levels were similar for the 1,000 and 2,000 IU/kg groups but varied in a dose-related manner for the other groups. Vitamin D did not significantly alter the tumor incidence in either the distal or the proximal colon. No significant differences in the labeling index were found in either the proximal or the distal colon. Within the distal colon, the proliferative zone increased in a dose-related manner. Distribution of labeled cells within the crypt compartments was not affected by dietary vitamin D. Bone and serum minerals in general were unaffected by dietary vitamin D. This study shows that, at this level of dietary calcium, vitamin D did not affect 1,2-dimethylhydrazine-induced colon carcinogenesis.

  14. The Associations of Novel Vitamin D3 Metabolic Gene CYP27A1 Polymorphism, Adiponectin/Leptin Ratio, and Metabolic Syndrome in Middle-Aged Taiwanese Males

    PubMed Central

    Liu, Chia-Chu; Huang, Chun-Nung; Lee, Yung-Chin; Chu, Chih-Sheng; Chang, Chu-Fen; Kuo, Po-Lin; Lai, Wen-Ter

    2015-01-01

    Metabolic syndrome (MetS) confers increased risks of cardiovascular disease (CVD). Both vitamin D3 and adipocytokines (especially adiponectin and leptin) have a great impact on CVD and MetS. In vitamin D3 metabolism, the vitamin D3 25-hydroxylase (CYP27A1) and 25-hydroxyvitamin D3 1-alpha-hydroxylase (CYP27B1) are two key enzymes. This study aimed to examine the influence of vitamin D3 CYP27 single nucleotide polymorphisms (SNPs) on adipocytokines and MetS. Cross-sectional data and DNA samples were collected from male volunteers (n = 649, age: 55.7 ± 4.7 years). Two tagging SNPs, CYP27A1 rs4674344 and CYP27B1 rs10877012, were selected from the HapMap project. MetS was significantly associated with the CYP27A1 rs4674344 SNP (P = 0.04) and the ratio of adiponectin/leptin (A/L ratio) was most correlated to the CYP27A1 rs4674344 SNP, appearing to be significantly lower in T-carriers than in AA subjects (3.7 ± 4.0 versus 5.1 ± 6.0, P = 0.001) and significantly negatively associated after adjustment. For each MetS component associated with the CYP27A1 rs4674344 SNP, the A/L ratios were significantly negative in preclinical stage (condition not meeting the individual criteria), except the blood pressure. In conclusion, CYP27A1 rs4674344 SNP, A/L ratio, and MetS are significantly associated and T-carriers might have a higher risk of developing MetS due to low A/L ratios in the preclinical stage. PMID:25628655

  15. Vitamin D3 Supplementation and Antibiotic Consumption – Results from a Prospective, Observational Study at an Immune-Deficiency Unit in Sweden

    PubMed Central

    Norlin, Anna-Carin; Hansen, Susanne; Wahren-Borgström, Emilie; Granert, Carl

    2016-01-01

    Background Vitamin D supplementation has been proposed to improve clinical symptoms during respiratory tract infections (RTIs), but results from randomized, placebo-controlled trials (RCT) are inconclusive. Previously, we performed an RCT in patients with various immune-disorders and observed that supplementation with 4000 IU vitamin D/day during 12 months significantly reduced antibiotic consumption and RTIs. This formed the basis for new guidelines at our unit; i.e. patients with insufficient levels of 25-hydroxyvitamin D (≤75 nmol/L) are now offered vitamin D supplementation. The aim of this prospective follow-up study was to evaluate the outcome of these new recommendations with regard to antibiotic consumption in our unit. Method 277 patients with insufficiency were supplemented with vitamin D3, 1500–1600 IU/day for 12 months. Each patient was its own control and data on antibiotic consumption was monitored 12 months before and 12 months after initiation of vitamin D3 supplementation. Results Vitamin D3 supplementation resulted in a significantly reduced antibiotic consumption, from 20 to 15 days/patient (p<0.05). The number of antibiotic-free patients increased from 52 to 81 after vitamin D3 supplementation; OR 1.79; 95% CI 1.20–2.66 (p<0.01). The number of antibiotic-prescriptions decreased significantly, a finding that mainly was attributed to a reduction of respiratory tract antibiotics (p<0.05). Subgroup analysis showed that only patients without immunoglobulin substitution (n = 135) had a significant effect of vitamin D supplementation. Conclusion Vitamin D3 supplementation of 1600 IE /day is safe to use in immunodeficient patients with 25-OHD levels less than 75 nmol/L and significantly reduced the antibiotic consumption in patients without immunoglobulin substitution. PMID:27657724

  16. The D3 Middleware Architecture

    NASA Technical Reports Server (NTRS)

    Walton, Joan; Filman, Robert E.; Korsmeyer, David J.; Lee, Diana D.; Mak, Ron; Patel, Tarang

    2002-01-01

    DARWIN is a NASA developed, Internet-based system for enabling aerospace researchers to securely and remotely access and collaborate on the analysis of aerospace vehicle design data, primarily the results of wind-tunnel testing and numeric (e.g., computational fluid-dynamics) model executions. DARWIN captures, stores and indexes data; manages derived knowledge (such as visualizations across multiple datasets); and provides an environment for designers to collaborate in the analysis of test results. DARWIN is an interesting application because it supports high-volumes of data. integrates multiple modalities of data display (e.g., images and data visualizations), and provides non-trivial access control mechanisms. DARWIN enables collaboration by allowing not only sharing visualizations of data, but also commentary about and views of data. Here we provide an overview of the architecture of D3, the third generation of DARWIN. Earlier versions of DARWIN were characterized by browser-based interfaces and a hodge-podge of server technologies: CGI scripts, applets, PERL, and so forth. But browsers proved difficult to control, and a proliferation of computational mechanisms proved inefficient and difficult to maintain. D3 substitutes a pure-Java approach for that medley: A Java client communicates (though RMI over HTTPS) with a Java-based application server. Code on the server accesses information from JDBC databases, distributed LDAP security services, and a collaborative information system. D3 is a three tier-architecture, but unlike 'E-commerce' applications, the data usage pattern suggests different strategies than traditional Enterprise Java Beans - we need to move volumes of related data together, considerable processing happens on the client, and the 'business logic' on the server-side is primarily data integration and collaboration. With D3, we are extending DARWIN to handle other data domains and to be a distributed system, where a single login allows a user

  17. SAFETY AND EFFICACY OF HIGH DOSE DAILY VITAMIN D3 SUPPLEMENTATION IN CHILDREN AND YOUNG ADULTS WITH SICKLE CELL DISEASE

    PubMed Central

    Dougherty, Kelly A.; Bertolaso, Chiara; Schall, Joan I.; Smith-Whitley, Kim; Stallings, Virginia A.

    2015-01-01

    Suboptimal vitamin D (vitD) status (<32 ng/ml) is ubiquitous among African American children with type SS sickle cell disease (SCD-SS). The vitD supplemental dose to normalize vitD status is unknown. Five to 20-year-old African-American children with (n=21) and without (n=23) SCD-SS were randomized to vitD3 supplementation (4,000 or 7,000 IU/day) and evaluated at 6- and 12-weeks for changes in vitD and SCD status. A dose was considered unsafe if serum calcium was elevated associated with elevated serum 25 hydroxyvitamin D (25(OH)D)). At baseline 95% of subjects with SCD-SS and 87% of healthy controls had suboptimal vitD status (mean ± SD, 19.2 ± 7.2 and 22.3 ± 9.3 ng/ml, respectively). After 12-weeks supplementation, both D3 doses were safe and well tolerated. Neither group achieved the a priori efficacy criterion of 25(OH)D ≥ 32 ng/ml in >80% of subjects (45% in SCD-SS and 63% in controls). However for both subjects with SCD-SS and healthy subjects by 12-weeks, deficient (< 20 ng/ml) vitD status was eliminated only in those receiving 7,000 IU/d. For subjects with SCD-SS, by 12-weeks there was a significant (all P<0.05) increase in fetal hemoglobin, decrease in HS-CRP, and reduction in the percentage of subjects with a high platelet count. PMID:25985241

  18. Super pharmacological levels of calcitriol (1,25-(OH)2D3) inhibits mineral deposition and decreases cell proliferation in a strain dependent manner in chicken mesenchymal stem cells undergoing osteogenic differentiation in vitro

    PubMed Central

    Pande, Vivek V.; Chousalkar, Kapil C.; Bhanugopan, Marie S.; Quinn, Jane C.

    2015-01-01

    The biologically active form of vitamin D3, calcitriol (1,25-(OH)2D3), plays a key role in mineral homeostasis and bone formation and dietary vitamin D3 deficiency is a major cause of bone disorders in poultry. Supplementary dietary cholecalciferol (25-hydroxyvitamin D, 25-OH), the precursor of calcitriol, is commonly employed to combat this problem; however, dosage must be carefully determined as excess dietary vitamin D can cause toxicity resulting in a decrease in bone calcification, hypercalcinemia and renal failure. Despite much research on the therapeutic administration of dietary vitamin D in humans, the relative sensitivity of avian species to exogenous vitamin D has not been well defined. In order to determine the effects of exogenous 1,25-(OH)2D3 during avian osteogenesis, chicken bone marrow-derived mesenchymal stem cells (BM-MSCs) were exposed to varying doses of 1,25-(OH)2D3 during in vitro osteogenic differentiation and examined for markers of early proliferation and osteogenic induction. Similar to humans and other mammals, poultry BM-MSCs were found to be highly sensitive to exogenous 1,25-(OH)2D3 with super pharmacological levels exerting significant inhibition of mineralization and loss of cell proliferation in vitro. Strain related differences were apparent, with BM-MCSs derived from layers strains showing a higher level of sensitivity to 1,25-(OH)2D3 than those from broilers. These data suggest that understanding species and strain specific sensitivities to 1,25-(OH)2D3 is important for optimizing bone health in the poultry industry and that use of avian BM-MSCs are a useful tool for examining underlying effects of genetic variation in poultry. PMID:26500277

  19. Safety and Efficacy of High-Dose Daily Vitamin D3 Supplementation in Children and Young Adults Infected With Human Immunodeficiency Virus

    PubMed Central

    Dougherty, Kelly A.; Schall, Joan I.; Zemel, Babette S.; Tuluc, Florin; Hou, Xiaoling; Rutstein, Richard M.; Stallings, Virginia A.

    2014-01-01

    Background Suboptimal vitamin D (vitD) status is common in children and young adults infected with human immunodeficiency virus (HIV). The vitD supplemental dose needed to normalize vitD status in this population is unknown. Methods In this double-blind trial, subjects infected with HIV ages 8.3 to 24.9 years were randomized to vitD3 supplementation of 4000 IU/day or 7000 IU/day and evaluated at 6 and 12 week for changes in vitD status and HIV indicators. A dose was considered unsafe if serum calcium was elevated (above age and sex-specific range) associated with elevated serum 25 hydroxyvitamin D (25(OH)D); >160 ng/mL). Results At baseline, 95% of subjects (n = 44; 43% with perinatally acquired HIV, 57% with behaviorally acquired HIV) had a suboptimal serum 25(OH)D concentration of <32 ng/mL (mean ± standard deviation, 19.3 ± 7.4; range, 4.4–33.6 ng/mL). After 12 weeks (main outcome) of D3 supplementation, both D3 doses were safe and well tolerated, with no evidence of elevation of serum calcium concentrations or deterioration in HIV immunologic or virologic status. Sufficient vitD status, defined as serum 25(OH)D ≥32 ng/mL, was achieved in 81% of all subjects, and only the 7000 IU/day group (86%) achieved this a priori efficacy criterion in >80% of subjects. Change in serum 25(OH)D did not differ between HIV acquisition groups. Conclusions A 7000 IU/day D3 supplementation was safe and effective in children and young adults infected with HIV. PMID:26625449

  20. Effects of 25-(OH)D3 on fecal Ca and P excretion, bone mineralization, Ca and P transporter mRNA expression and performance in growing female pigs.

    PubMed

    Regassa, Alemu; Adhikari, Roshan; Nyachoti, Charles M; Kim, Woo Kyun

    2015-01-01

    A study was conducted to examine the effects of 25-hydroxyvitamin D3 (25-(OH)D3) on fecal Ca and P excretion, bone mineralization, performance and the mRNA expression of intestinal transporter genes in growing female pigs. Sixty-day old gilts (n = 24) with an average initial BW of 23.13 ± 1.49 kg were randomly allocated to a control diet (diet 1) containing wheat/corn/soybean meal and 150 IU kg(-1) of Vitamin D3, diet 1 + 50 μg of 25-(OH)D3 kg(-1) (diet 2) and diet 1 + 100 μg of 25-(OH)D3 kg(-1) (diet 3). The pigs were housed in an individual pen and had ad libitum access to feed and water for 42 days, and BWG and feed intake were measured weekly. Measures of bone mineralization and expression of Ca and P transporters mRNA were analyzed using Dual Energy X-Ray Absortiometry (DEXA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Data were analyzed using GLM procedure of the Statistical Analysis System (SAS Institute version 9.2). Fecal Ca and P concentration were significantly reduced (P ≤ 0.05) in pigs fed diets 2 and 3 compared with the control diet. Supplementation of 25-(OH)D3 did not significantly improve bone mineralization, animal performance and intestinal transporters mRNA expression except for SLC34A1, a sodium-dependent phosphate transporter 1. In conclusion, supplementation of 25-(OH)D3 in swine nutrition may not improve animal performance but has the potential to reduce environmental pollution by increasing dietary Ca and P retention while reducing their excretion.

  1. Serum 25-Hydroxyvitamin D in Patients with Major Depressive Disorder

    PubMed Central

    DANA-ALAMDARI, Leila; KHEIROURI, Sorayya; NOORAZAR, Seyed Gholamreza

    2015-01-01

    Background: We investigated the association between serum 25(OH) D levels and depressive symptoms in patients with major depressive disorder (MDD). Methods: Eighty-five adults, 44 drug free patients with MDD and 41 apparently healthy controls, participated in the study. The Hamilton Depression Rating Scale was used to assess severity of major depression. Mental health of the controls was assessed according to DSM-IV criteria. Stress level of the participants was assessed by the Holmes and Rahe stress scale. Serum 25(OH) D levels was measured by immunochemiluminescence assay. Vitamin D deficiency was defined as a serum 25(OH) D concentration of lower than 20 ng/ml. Results: Depressed patients had the higher levels of stress. There was a positive correlation between stress level and disease severity (r= 0.32, P= 0.03). In total participants, mean percentage of vitamin D deficiency was 77.6% with 75% in patients and 80.5% in the healthy subjects. There were no differences between the two groups in serum 25(OH) D levels and percentage of subjects with the vitamin deficiency. A negative correlation was observed between disease severity and serum 25(OH) D level of patients with depression episodes < 2 y (r= −0.38, P = 0.08) and winter samples (samples collected and measured from December to march, r= −0.62, P = 0.004). Conclusion: Serum 25(OH) D levels were not associated with depression. However, the inverse relationship between levels of vitamin D and depressive symptoms in current depression episodes and in sun-deprived season warrants further investigation. PMID:26284211

  2. Serum 25-hydroxyvitamin D and functional outcomes in the elderly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this paper is to consider key evidence that treatment of vitamin D insufficiency has measurable clinical benefits for the musculoskeletal system in the elderly. The outcomes considered are increased bone mass, decreased rates of bone loss, improved muscle performance, reduced risk o...

  3. High-Dose Vitamin D3 Supplementation in Children and Young Adults with HIV: A Randomized, Placebo-Controlled Trial

    PubMed Central

    Stallings, Virginia A.; Schall, Joan I.; Hediger, Mary L.; Zemel, Babette S.; Tuluc, Florin; Dougherty, Kelly A.; Samuel, Julia L.; Rutstein, Richard M.

    2014-01-01

    Background Suboptimal vitamin D status is prevalent in HIV-infected patients and associated with increased risk of disease severity and morbidity. We aimed to determine 12-mo safety and efficacy of daily 7000IU vitamin D3 (vitD3) vs placebo to sustain increased serum 25-hydroxyvitamin D (25(OH)D) and improve immune status in HIV-infected subjects. Methods This was a double-blind trial of perinatally- (PHIV) or behaviorally-acquired (BHIV) HIV-infected subjects (5.0–24.9y). Safety, 25(OH)D-related parameters, and immune status were assessed at baseline, 3, 6, and 12 months. Results Fifty-eight subjects enrolled (67% male, 85% African-American, 64% BHIV) and 50 completed with no safety concerns. In unadjusted analyses, there were no differences between randomization groups at baseline; at 3, 6, and 12 months, 25(OH)D was higher with supplementation than baseline and higher than with placebo (P<0.05). In adjusted mixed models, in the supplementation group, the fixed effect of 25(OH)D was higher (P<0.001). Percentage of naïve T helper cells (Th naïve%) were significantly (P<0.01) and T helper cells (CD4%) marginally (P<0.10) increased with supplementation in those taking highly active antiretroviral therapy (HAART), and RNA viral load was reduced (P ≤ 0.05). In exploratory linear models, change in 25(OH)D predicted RNA viral load at 3 and 12 months and CD4% at 3 months (P<0.05). Conclusions Daily 7000IU vitD3 for 12 months was safe in HIV-infected subjects and effective in increasing 25(OH)D. Supplementation improved in some clinically important HIV immune markers in subjects on HAART. Adjunct therapy with high-dose, daily vitD3 for HIV-infected subjects and for those on/off HAART requires further investigation. PMID:24988118

  4. Effect of Vitamin D3 Supplementation in Black and in White Children: A Randomized, Placebo-Controlled Trial

    PubMed Central

    Moore, Charity G.; Yabes, Jonathan; Olabopo, Flora; Haralam, Mary Ann; Comer, Diane; Bogusz, Jaimee; Nucci, Anita; Sereika, Susan; Dunbar-Jacob, Jacqueline; Holick, Michael F.; Greenspan, Susan L.

    2015-01-01

    Context: Dosages of vitamin D necessary to prevent or treat vitamin D deficiency in children remain to be clarified. Objective: To determine the effects of vitamin D3 1000 IU/d on serum 25-hydroxyvitamin D [25(OH)D], PTH, and markers of bone turnover (osteocalcin and collagen type 1 cross-linked C-telopeptide) in black children and white children, and to explore whether there is a threshold level of 25(OH)D associated with maximal suppression of serum PTH concentration. Design: Healthy 8- to 14-year-old Pittsburgh-area black (n = 84) and white (n = 73) children not receiving vitamin supplements, enrolled from October through March from 2008 through 2011, were randomized to vitamin D3 1000 IU or placebo daily for 6 months. Results: The mean baseline concentration of 25(OH)D was <20 ng/mL in both the vitamin D-supplemented group and the placebo group (19.8 ± 7.6 and 18.8 ± 6.9 ng/mL, respectively). The mean concentration was higher in the supplemented group than in the placebo group at 2 months (26.4 ± 8.1 vs 18.9 ± 8.1 ng/mL; P < .0001) and also at 6 months (26.7 ± 7.6 vs 22.4 ± 7.3; P = .003), after adjusting for baseline 25(OH)D, race, gender, pubertal status, dietary vitamin D intake, body mass index, and sunlight exposure. Increases were only significant in black children, when examined by race. The association between 25(OH)D and PTH concentrations was inverse and linear, without evidence of a plateau. Overall, vitamin D supplementation had no effect on PTH and bone turnover. Conclusions: Vitamin D3 supplementation with 1000 IU/d in children with mean baseline 25(OH)D concentration <20 ng/mL effectively raised their mean 25(OH)D concentration to ≥20 ng/mL but failed to reach 30 ng/mL. Vitamin D supplementation had no effect on PTH concentrations. PMID:26091202

  5. Safety and Efficacy of High-dose Daily Vitamin D3 Supplementation in Children and Young Adults With Sickle Cell Disease.

    PubMed

    Dougherty, Kelly A; Bertolaso, Chiara; Schall, Joan I; Smith-Whitley, Kim; Stallings, Virginia A

    2015-07-01

    Suboptimal vitamin D (vit D) status (<32 ng/mL) is ubiquitous among African American children with type SS sickle cell disease (SCD-SS). The vit D supplemental dose to normalize vit D status is unknown. Five to 20-year-old African American children with (n=21) and without (n=23) SCD-SS were randomized to vit D3 supplementation (4000 or 7000 IU/d) and evaluated at 6 and 12 weeks for changes in vit D and SCD status. A dose was considered unsafe if serum calcium was elevated associated with elevated serum 25 hydroxyvitamin D (25(OH)D). At baseline 95% of subjects with SCD-SS and 87% of healthy controls had suboptimal vit D status (mean±SD, 19.2±7.2 and 22.3±9.3 ng/mL, respectively). After 12 weeks supplementation, both D3 doses were safe and well tolerated. Neither group achieved the a priori efficacy criterion of 25(OH)D≥32 ng/mL in >80% of subjects (45% in SCD-SS and 63% in controls). However, for both subjects with SCD-SS and healthy subjects by 12 weeks, deficient (<20 ng/mL) vit D status was eliminated only in those receiving 7000 IU/d. For subjects with SCD-SS, by 12 weeks there was a significant (all P<0.05) increase in fetal hemoglobin, decrease in high-sensitivity C-reactive protein, and reduction in the percentage of subjects with a high platelet count.

  6. Vitamin D3 metabolism in dogs.

    PubMed

    Hazewinkel, H A W; Tryfonidou, M A

    2002-11-29

    Plasma concentrations of the main vitamin D(3) metabolites (i.e., 25(OH)D(3), 1,25(OH)(2)D(3), and 24,25(OH)(2)D(3)) were measured in 14 weeks old large- and small-breed dogs (adult body weight 60 kg vs. 6 kg), raised under the same conditions. Levels of 25(OH)D(3) (approx. 22 microg/l) and 1,25(OH)(2)D(3) (approx. 40 ng/l) were similar in both groups, whereas plasma 24,25(OH)(2)D(3) concentrations were lower in large-breed dogs (7 microg/l vs. 70 microg/l, large- vs. small-breed dogs, respectively). The lower plasma 24,25(OH)(2)D(3) concentrations could be explained by the higher plasma GH and IGF-I concentrations in the large- vs. small-breed dogs, and these hormones are known to suppress 24-hydroxylation. Plasma 24,25(OH)(2)D(3) concentrations increased during Ca supplementation in small-breed but not in large-breed dogs (100 microg/l vs. 7 microg/l, respectively). Hypophosphatemia induced by a high dietary Ca content was only seen together with increased plasma 1,25(OH)(2)D(3) concentrations in euparathyroid dogs and not in hypoparathyroid dogs. Hyperparathyroidism due to Ca deficiency was accompanied by increased plasma 1,25(OH)(2)D(3) concentrations and decreased plasma 24,25(OH)(2)D(3) concentrations in both large- and small-breed dogs, together with generalized osteoporosis. Large-breed pups fed on a standard diet supplemented with Ca and P had decreased plasma concentrations of both 25(OH)D(3) and 1,25(OH)(2)D(3), which may indicate an increased clearance of these metabolites; the low plasma concentrations of the di-hydroxylated vitamin D metabolites were considered responsible for the disturbance in cartilage maturation (i.e., osteochondrosis) in these dogs. Even lower concentrations of all vitamin D(3) metabolites were seen in young dogs raised on a vitamin D(3)-deficient diet, and led to disturbed osteoid and cartilage mineralization (i.e., rickets). These studies indicate that there is a hierarchy of factors regulating vitamin D(3) metabolism in dogs

  7. Influence of Vitamin D Status and Vitamin D3 Supplementation on Genome Wide Expression of White Blood Cells: A Randomized Double-Blind Clinical Trial

    PubMed Central

    Hossein-nezhad, Arash; Spira, Avrum; Holick, Michael F.

    2013-01-01

    Background Although there have been numerous observations of vitamin D deficiency and its links to chronic diseases, no studies have reported on how vitamin D status and vitamin D3 supplementation affects broad gene expression in humans. The objective of this study was to determine the effect of vitamin D status and subsequent vitamin D supplementation on broad gene expression in healthy adults. (Trial registration: ClinicalTrials.gov NCT01696409). Methods and Findings A randomized, double-blind, single center pilot trial was conducted for comparing vitamin D supplementation with either 400 IUs (n = 3) or 2000 IUs (n = 5) vitamin D3 daily for 2 months on broad gene expression in the white blood cells collected from 8 healthy adults in the winter. Microarrays of the 16 buffy coats from eight subjects passed the quality control filters and normalized with the RMA method. Vitamin D3 supplementation that improved serum 25-hydroxyvitamin D concentrations was associated with at least a 1.5 fold alteration in the expression of 291 genes. There was a significant difference in the expression of 66 genes between subjects at baseline with vitamin D deficiency (25(OH)D<20 ng/ml) and subjects with a 25(OH)D>20 ng/ml. After vitamin D3 supplementation gene expression of these 66 genes was similar for both groups. Seventeen vitamin D-regulated genes with new candidate vitamin D response elements including TRIM27, CD83, COPB2, YRNA and CETN3 which have been shown to be important for transcriptional regulation, immune function, response to stress and DNA repair were identified. Conclusion/Significance Our data suggest that any improvement in vitamin D status will significantly affect expression of genes that have a wide variety of biologic functions of more than 160 pathways linked to cancer, autoimmune disorders and cardiovascular disease with have been associated with vitamin D deficiency. This study reveals for the first time molecular finger prints that help explain the

  8. A Randomized Trial of Vitamin D3 Supplementation in Children: Dose-Response Effects on Vitamin D Metabolites and Calcium Absorption

    PubMed Central

    Laing, E. M.; Hill Gallant, K. M.; Hall, D. B.; McCabe, G. P.; Hausman, D. B.; Martin, B. R.; Warden, S. J.; Peacock, M.; Weaver, C. M.

    2013-01-01

    Context: Changes in serum vitamin D metabolites and calcium absorption with varying doses of oral vitamin D3 in healthy children are unknown. Objective: Our objective was to examine the dose-response effects of supplemental vitamin D3 on serum vitamin D metabolites and calcium absorption in children living at two U.S. latitudes. Design: Black and white children (n = 323) participated in a multisite (U.S. latitudes 34° N and 40° N), triple-masked trial. Children were randomized to receive oral vitamin D3 (0, 400, 1000, 2000, and 4000 IU/d) and were sampled over 12 weeks in winter. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured using RIA and intact PTH (iPTH) by immunoradiometric assay. Fractional calcium absorption was determined from an oral stable isotope 44Ca (5 mg) in a 150-mg calcium meal. Nonlinear and linear regression models were fit for vitamin D metabolites, iPTH, and calcium absorption. Results: The mean baseline 25(OH)D value for the entire sample was 70.0 nmol/L. Increases in 25(OH)D depended on dose with 12-week changes ranging from −10 nmol/L for placebo to 76 nmol/L for 4000 IU. Larger 25(OH)D gains were observed for whites vs blacks at the highest dose (P < .01). Gains for 1,25(OH)2D were not significant (P = .07), and decreases in iPTH were not dose-dependent. There was no dose effect of vitamin D on fractional calcium absorption when adjusted for pill compliance, race, sex, or baseline 25(OH)D. Conclusion: Large increases in serum 25(OH)D with vitamin D3 supplementation did not increase calcium absorption in healthy children living at 2 different latitudes. Supplementation with 400 IU/d was sufficient to maintain wintertime 25(OH)D concentrations in healthy black, but not white, children. PMID:24092833

  9. Leptin stimulates fibroblast growth factor 23 expression in bone and suppresses renal 1alpha,25-dihydroxyvitamin D3 synthesis in leptin-deficient mice.

    PubMed

    Tsuji, Kiyomi; Maeda, Toyonobu; Kawane, Tetsuya; Matsunuma, Ayako; Horiuchi, Noboru

    2010-08-01

    Leptin is the LEP (ob) gene product secreted by adipocytes. We previously reported that leptin decreases renal expression of the 25-hydroxyvitamin D(3) 1alpha-hydroxylase (CYP27B1) gene through the leptin receptor (ObRb) by indirectly acting on the proximal tubules. This study focused on bone-derived fibroblast growth factor 23 (FGF-23) as a mediator of the influence of leptin on renal 1alpha-hydroxylase mRNA expression in leptin-deficient ob/ob mice. Exposure to leptin (200 ng/mL) for 24 hours stimulated FGF-23 expression by primary cultured rat osteoblasts. Administration of leptin (4 mg/kg i.p. at 12-hour intervals for 2 days) to ob/ob mice markedly increased the serum FGF-23 concentration while significantly reducing the serum levels of calcium, phosphate, and 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. Administration of FGF-23 (5 microg i.p. at 12-hour intervals for 2 days) to ob/ob mice suppressed renal 1alpha-hydroxylase mRNA expression. The main site of FGF-23 mRNA expression was the bone, and leptin markedly increased the FGF-23 mRNA level in ob/ob mice. In addition, leptin significantly reduced 1alpha-hydroxylase and sodium-phosphate cotransporters (NaP(i)-IIa and NaP(i)-IIc) mRNA levels but did not affect Klotho mRNA expression in the kidneys of ob/ob mice. Furthermore, the serum FGF-23 level and renal expression of 1alpha-hydroxylase mRNA were not influenced by administration of leptin to leptin receptor-deficient (db/db) mice. These results indicate that leptin directly stimulates FGF-23 synthesis by bone cells in ob/ob mice, suggesting that inhibition of renal 1,25(OH)(2)D(3) synthesis in these mice is at least partly due to elevated bone production of FGF-23.

  10. Randomized placebo-controlled trial of high-dose prenatal third-trimester vitamin D3 supplementation in Bangladesh: the AViDD trial

    PubMed Central

    2013-01-01

    Background Antenatal vitamin D status may be associated with the risk of adverse pregnancy and neonatal outcomes; however, the benefits of vitamin D supplementation during pregnancy remain unknown. Methods We conducted a double-blind placebo-controlled randomized trial to evaluate the effect of high-dose prenatal 3rd trimester vitamin D3 supplementation on maternal and neonatal (cord blood) serum 25-hydroxyvitamin D (25(OH)D) concentration (primary biochemical efficacy outcome) and maternal serum calcium concentration (primary safety measure). Eligibility criteria were pregnant women aged 18 to <35 years, at 26 to 29 weeks gestation, and residing in Dhaka, Bangladesh. 160 women were randomized by 1:1 allocation to one of two parallel intervention groups; placebo (n = 80) or 35,000 IU/week of vitamin D3 (n = 80) until delivery. All participants, study personnel and study investigators were blind to treatment allocation. Results Mean maternal 25(OH)D concentration was similar in the vitamin D and placebo groups at baseline (45 vs. 44 nmol/L; p = 0.66), but was significantly higher in the vitamin D group vs. placebo group among mothers at delivery (134 vs. 38 nmol/L; p < 0.001) and newborns (cord blood: 103 vs. 39; p < 0.001). In the vitamin D group, 95% of neonates and 100% of mothers attained 25(OH)D >50 nmol/L, versus 21% mothers and 19% of neonates in the placebo group. No participants met criteria for hypercalcemia, there were no known supplement-related adverse events, and major pregnancy outcomes were similar between groups. Conclusions Antenatal 3rd-trimester vitamin D3 supplementation (35,000 IU/week) significantly raised maternal and cord serum 25(OH)D concentrations above 50 nmol/L in almost all participants without inducing hypercalcemia or other observed safety concerns. Doses up to 35,000 IU/week may be cautiously used in further research aimed at establishing the clinical effects and safety of vitamin D3 supplementation in

  11. Vitamin D3 and brain development.

    PubMed

    Eyles, D; Brown, J; Mackay-Sim, A; McGrath, J; Feron, F

    2003-01-01

    Evidence for the presence of the vitamin D receptor in brain implies this vitamin may have some function in this organ. This study investigates whether vitamin D(3) acts during brain development. We demonstrate that rats born to vitamin D(3)-deficient mothers had profound alterations in the brain at birth. The cortex was longer but not wider, the lateral ventricles were enlarged, the cortex was proportionally thinner and there was more cell proliferation throughout the brain. There were reductions in brain content of nerve growth factor and glial cell line-derived neurotrophic factor and reduced expression of p75(NTR), the low-affinity neurotrophin receptor. Our findings would suggest that low maternal vitamin D(3) has important ramifications for the developing brain. PMID:12710973

  12. Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia.

    PubMed

    Colby, Jennifer K; Abdulnour, Raja-Elie E; Sham, Ho Pan; Dalli, Jesmond; Colas, Romain A; Winkler, Jeremy W; Hellmann, Jason; Wong, Blenda; Cui, Ye; El-Chemaly, Souheil; Petasis, Nicos A; Spite, Matthew; Serhan, Charles N; Levy, Bruce D

    2016-07-01

    Acute lung injury is a life-threatening condition caused by disruption of the alveolar-capillary barrier leading to edema, influx of inflammatory leukocytes, and impaired gas exchange. Specialized proresolving mediators biosynthesized from essential fatty acids, such as docosahexaenoic acid, have tissue protective effects in acute inflammation. Herein, we found that the docosahexaenoic acid-derived mediator resolvin D3 (RvD3): 4S,11R,17S-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid was present in uninjured lungs, and increased significantly 24 to 72 hours after hydrochloric acid-initiated injury. Because of its delayed enzymatic degradation, we used aspirin-triggered (AT)-RvD3: 4S,11R,17R-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid, a 17R-epimer of RvD3, for in vivo experiments. Histopathological correlates of acid injury (alveolar wall thickening, edema, and leukocyte infiltration) were reduced in mice receiving AT-RvD3 1 hour after injury. AT-RvD3-treated mice had significantly reduced edema, as demonstrated by lower wet/dry weight ratios, increased epithelial sodium channel γ expression, and more lymphatic vessel endothelial hyaluronan receptor 1-positive vascular endothelial growth factor receptor 3-positive lymphatic vessels. Evidence for counterregulation of NF-κB by RvD3 and AT-RvD3 was seen in vitro and by AT-RvD3 in vivo. Increases in lung epithelial cell proliferation and bronchoalveolar lavage fluid levels of keratinocyte growth factor were observed with AT-RvD3, which also promoted cutaneous re-epithelialization. Together, these data demonstrate protective actions of RvD3 and AT-RvD3 for injured mucosa that accelerated restoration of epithelial barrier and function. PMID:27171898

  13. "Scrubbing" Data for D3M

    ERIC Educational Resources Information Center

    Mercurius, Neil

    2005-01-01

    Data-driven decision-making (D3M) appears to be the new buzz phrase for this century, the information age. On the education front, teachers and administrators are engaging in data-centered dialog in grade-level meetings, lounges, hallways, and classrooms as they brainstorm toward closing the gap in student achievement. Clearly, such discussion…

  14. 42 CFR 52d.3 - Eligibility.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.3 Eligibility. To be eligible for a grant under this part, an applicant..., affiliated teaching hospital, or specialized cancer institute; and (b) Located in a State, the District...

  15. 42 CFR 52d.3 - Eligibility.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.3 Eligibility. To be eligible for a grant under this part, an applicant..., affiliated teaching hospital, or specialized cancer institute; and (b) Located in a State, the District...

  16. 42 CFR 52d.3 - Eligibility.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.3 Eligibility. To be eligible for a grant under this part, an applicant..., affiliated teaching hospital, or specialized cancer institute; and (b) Located in a State, the District...

  17. 42 CFR 52d.3 - Eligibility.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.3 Eligibility. To be eligible for a grant under this part, an applicant..., affiliated teaching hospital, or specialized cancer institute; and (b) Located in a State, the District...

  18. 42 CFR 52d.3 - Eligibility.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.3 Eligibility. To be eligible for a grant under this part, an applicant..., affiliated teaching hospital, or specialized cancer institute; and (b) Located in a State, the District...

  19. Changes in the vitamin D endocrine system and bone turnover after oral vitamin D3 supplementation in healthy adults: results of a randomised trial

    PubMed Central

    2012-01-01

    Background There is uncertainty as to which intake of vitamin D is needed to suppress PTH and maintain normal bone metabolism throughout winter at northern latitudes. We aimed to investigate whether four weeks’ daily supplementation with 10 μg vitamin D3 from fish oil produced a greater change in serum vitamin D metabolites, parathyroid hormone, and bone turnover in healthy adults compared with solid multivitamin tablets. Furthermore, it was studied whether age, gender, ethnic background, body mass index, or serum concentrations at baseline predicted the magnitude of change in these parameters. Methods Healthy adults aged 19–48 years living in Oslo, Norway (59°N) were randomised to receive a daily dose of 10 μg vitamin D3 given as fish oil capsules or multivitamin tablets during four weeks in late winter. Serum samples from baseline and after 28 days were analysed for 25-hydroxyvitamin D (s-25(OH)D), 1,25-dihydroxyvitamin D (s-1,25(OH)2D), intact parathyroid hormone (s-iPTH), and osteoclast-specific tartrate-resistant acid phosphatase 5b (s-TRACP). Fifty-five eligible participants completed the intervention (74% of those randomised). Results S-25(OH)D increased by mean 34.1 (SD 13.1) nmol/l, p < 0.001; s-iPTH decreased by mean 1.2 (SD 2.5) pmol/l, p = 0.001; s-1,25(OH)2D increased by mean 13 (SD 48) pmol/l, p = 0.057; and s-TRACP increased by mean 0.38 (SD 0.33) U/l, p < 0.001. For all these parameters, there was no difference between fish oil and multivitamin formulation. Baseline concentrations were the only independent predictors of changes in biochemical parameters. Conclusions Four weeks of daily supplementation with 10 μg vitamin D3 decreased mean s-iPTH and increased s-TRACP concentration, and this did not differ by mode of administration. Our results suggest an increased bone resorption following vitamin D supplementation in young individuals, despite a decrease in parathyroid hormone levels. Trial Registration Clinical

  20. Automated D/3 to Visio Analog Diagrams

    2000-08-10

    ADVAD1 reads an ASCII file containing the D/3 DCS MDL input for analog points for a D/3 continuous database. It uses the information in the files to create a series of Visio files representing the structure of each analog chain, one drawing per Visio file. The actual drawing function is performed by Visio (requires Visio version 4.5+). The user can configure the program to select which fields in the database are shown on the diagrammore » and how the information is to be presented. This gives a visual representation of the structure of the analog chains, showing selected fields in a consistent manner. Updating documentation can be done easily and the automated approach eliminates human error in the cadding process. The program can also create the drawings far faster than a human operator is capable, able to create approximately 270 typical diagrams in about 8 minutes on a Pentium II 400 MHz PC. The program allows for multiple option sets to be saved to provide different settings (i.e., different fields, different field presentations, and /or different diagram layouts) for various scenarios or facilities on one workstation. Option sets may be exported from the Windows registry to allow duplication of settings on another workstation.« less

  1. Effect of 24,25-dihydroxyvitamin D3 on 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) metabolism in vitamin D-deficient rats infused with 1,25-(OH)2D3

    SciTech Connect

    Yamato, H.; Matsumoto, T.; Fukumoto, S.; Ikeda, K.; Ishizuka, S.; Ogata, E.

    1989-01-01

    Previous studies revealed that administration of 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) to calcium (Ca)-deficient rats causes a dose-dependent reduction in markedly elevated serum 1,25-(OH)2D3 level. Although the results suggested that the metabolism of 1,25-(OH)2D3 was accelerated by 24,25-(OH)2D3, those experiments could not define whether the enhanced metabolism of 1,25-(OH)2D3 played a role in the reduction in the serum 1,25-(OH)2D3 level. In the present study, in order to address this issue more specifically, serum 1,25-(OH)2D3 was maintained solely by exogenous administration through miniosmotic pumps of 1,25-(OH)2D3 into vitamin D-deficient rats. Thus, by measuring the serum 1,25-(OH)2D3 concentration, the effect of 24,25-(OH)2D3 on the MCR of 1,25-(OH)2D3 could be examined. Administration of 24,25-(OH)2D3 caused a dose-dependent enhancement in the MCR of 1,25-(OH)2D3, and 1 microgram/100 g rat.day 24,25-(OH)2D3, which elevated serum 24,25-(OH)2D3 to 8.6 +/- 1.3 ng/ml, significantly increased MCR and suppressed serum levels of 1,25-(OH)2D3. The effect of 24,25-(OH)2D3 on 1,25-(OH)2D3 metabolism developed with a rapid time course, and the recovery of iv injected (1 beta-3H)1,25-(OH)2D3 in blood was significantly reduced within 1 h. In addition, there was an increase in radioactivity in the water-soluble fraction of serum as well as in urine, suggesting that 1,25-(OH)2D3 is rapidly degraded to a water-soluble metabolite(s). Furthermore, the reduction in serum 1,25-(OH)2D3 was associated with a reduction in both serum and urinary Ca levels. Because the conversion of (3H)24,25-(OH)2D3 to (3H)1,24,25-(OH)2D3 or other metabolites was minimal in these rats, 24,25-(OH)2D3 appears to act without being converted into other metabolites. These results demonstrate that 24,25-(OH)2D3 rapidly stimulates the metabolism of 1,25-(OH)2D3 and reduces its serum level.

  2. Metabolism of 20-hydroxyvitamin D3 by mouse liver microsomes.

    PubMed

    Cheng, Chloe Y S; Slominski, Andrzej T; Tuckey, Robert C

    2014-10-01

    20-Hydroxyvitamin D3 [20(OH)D3], the major product of CYP11A1 action on vitamin D3, is biologically active and like 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can inhibit proliferation and promote differentiation of a range of cells, and has anti-inflammatory properties. However, unlike 1,25(OH)2D3, it does not cause toxic hypercalcemia at high doses and is therefore a good candidate for therapeutic use to treat hyperproliferative and autoimmune disorders. In this study we analyzed the ability of mouse liver microsomes to metabolize 20(OH)D3. The two major products were identified from authentic standards as 20,24-dihydroxyvitamin D3 [20,24(OH)2D3] and 20,25-dihydroxyvitamin D3 [20,25(OH)2D3]. The reactions for synthesis of these two products from 20(OH)D3 displayed similar Km values suggesting that they were catalyzed by the same cytochrome P450. Some minor metabolites were produced by reactions with higher Km values for 20(OH)D3. Some metabolites gave mass spectra suggesting that they were the result of hydroxylation followed by dehydrogenation. One product had an increase in the wavelength for maximum absorbance from 263nm seen for 20(OH)D3, to 290nm, suggesting a new double bond was interacting with the vitamin D-triene chromophore. The two major products, 20,24(OH)2D3 and 20,25(OH)2D3 have both previously been shown to have higher potency for inhibition of colony formation by melanoma cells than 20(OH)D3, thus it appears that metabolism of 20(OH)D3 by mouse liver microsomes can generate products with enhanced activity. PMID:25138634

  3. Metabolism of 20-hydroxyvitamin D3 by mouse liver microsomes

    PubMed Central

    Cheng, Chloe Y.S.; Slominski, Andrzej T.; Tuckey, Robert C.

    2014-01-01

    20-Hydroxyvitamin D3 [20(OH)D3], the major product of CYP11A1 action on vitamin D3, is biologically active and like 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can inhibit proliferation and promote differentiation of a range of cells, and has anti-inflammatory properties. However, unlike 1,25(OH)2D3, it does not cause toxic hypercalcemia at high doses and is therefore a good candidate for therapeutic use to treat hyperproliferative and autoimmune disorders. In this study we analyzed the ability of mouse liver microsomes to metabolize 20(OH)D3. The two major products were identified from authentic standards as 20,24-dihydroxyvitamin D3 [20,24(OH)2D3] and 20,25-dihydroxyvitamin D3 [20,25(OH)2D3]. The reactions for synthesis of these two products from 20(OH)D3 displayed similar Km values suggesting that they were catalyzed by the same cytochrome P450. Some minor metabolites were produced by reactions with higher Km values for 20(OH)D3. Some metabolites gave mass spectra suggesting that they were the result of hydroxylation followed by dehydrogenation. One product had an increase in the wavelength for maximum absorbance from 263 nm seen for 20(OH)D3, to 290 nm, suggesting a new double bond was interacting with the vitamin D-triene chromophore. The two major products, 20,24(OH)2D3 and 20,25(OH)2D3 have both previously been shown to have higher potency for inhibition of colony formation by melanoma cells than 20(OH)D3, thus it appears that metabolism of 20(OH)D3 by mouse liver microsomes can generate products with enhanced activity. PMID:25138634

  4. High Affinity Dopamine D3 Receptor (D3R)-Selective Antagonists Attenuate Heroin Self-Administration in Wild-Type but not D3R Knockout Mice

    PubMed Central

    2015-01-01

    The dopamine D3 receptor (D3R) is a promising target for the development of pharmacotherapeutics to treat substance use disorders. Several D3R-selective antagonists are effective in animal models of drug abuse, especially in models of relapse. Nevertheless, poor bioavailability, metabolic instability, and/or predicted toxicity have impeded success in translating these drug candidates to clinical use. Herein, we report a series of D3R-selective 4-phenylpiperazines with improved metabolic stability. A subset of these compounds was evaluated for D3R functional efficacy and off-target binding at selected 5-HT receptor subtypes, where significant overlap in SAR with D3R has been observed. Several high affinity D3R antagonists, including compounds 16 (Ki = 0.12 nM) and 32 (Ki = 0.35 nM), showed improved metabolic stability compared to the parent compound, PG648 (6). Notably, 16 and the classic D3R antagonist SB277011A (2) were effective in reducing self-administration of heroin in wild-type but not D3R knockout mice. PMID:26203768

  5. 21 CFR 582.5953 - Vitamin D3.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Vitamin D3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D3. (a) Product. Vitamin D3. (b) Conditions of use. This substance is...

  6. 21 CFR 582.5953 - Vitamin D 3.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Vitamin D 3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D 3. (a) Product. Vitamin D3. (b) Conditions of use. This substance...

  7. 21 CFR 582.5953 - Vitamin D3.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Vitamin D3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D3. (a) Product. Vitamin D3. (b) Conditions of use. This substance is...

  8. 21 CFR 582.5953 - Vitamin D 3.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Vitamin D 3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D 3. (a) Product. Vitamin D3. (b) Conditions of use. This substance...

  9. 21 CFR 582.5953 - Vitamin D3.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Vitamin D3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D3. (a) Product. Vitamin D3. (b) Conditions of use. This substance is...

  10. Cosmic D- and DF-strings from D3D3: Black strings and BPS limit

    SciTech Connect

    Kim, Taekyung; Kim, Yoonbai; Kyae, Bumseok; Lee, Jungjai

    2008-03-15

    We study D- and DF-strings in a D3D3 system by using Dirac-Born-Infeld type action. In the presence of an electric flux from the transverse direction, we discuss gravitating thick D-string solutions of a spatial manifold, S{sup 2}xR{sup 1}, in which straight D-strings stretched along the R{sup 1} direction are attached to the south and north poles of the two-sphere. There is a horizon along its equator, which means the structure of black strings is formed. We also discuss the BPS limit for thin parallel D- and DF-strings in both flat and curved spacetime. We obtain the BPS sum rule for an arbitrarily-separated multistring configuration with a Gaussian type tachyon potential. At the site of each thin BPS D(F)-string, the pressure takes a finite value. We find that there exists a maximum deficit angle {pi} in the conical geometry induced by thin BPS D- and DF-strings.

  11. Structure of the Human Dopamine D3 Receptor in Complex with a D2/D3 Selective Antagonist

    SciTech Connect

    Chien, Ellen Y.T.; Liu, Wei; Zhao, Qiang; Katritch, Vsevolod; Han, Gye Won; Hanson, Michael A.; Shi, Lei; Newman, Amy Hauck; Javitch, Jonathan A.; Cherezov, Vadim; Stevens, Raymond C.

    2010-11-30

    Dopamine modulates movement, cognition, and emotion through activation of dopamine G protein-coupled receptors in the brain. The crystal structure of the human dopamine D3 receptor (D3R) in complex with the small molecule D2R/D3R-specific antagonist eticlopride reveals important features of the ligand binding pocket and extracellular loops. On the intracellular side of the receptor, a locked conformation of the ionic lock and two distinctly different conformations of intracellular loop 2 are observed. Docking of R-22, a D3R-selective antagonist, reveals an extracellular extension of the eticlopride binding site that comprises a second binding pocket for the aryl amide of R-22, which differs between the highly homologous D2R and D3R. This difference provides direction to the design of D3R-selective agents for treating drug abuse and other neuropsychiatric indications.

  12. HoxD3 accelerates wound healing in diabetic mice

    SciTech Connect

    Hansen, Scott L.; Myers, Connie A.; Charboneau, Aubri; Young, David M.; and Boudreau, Nancy

    2003-12-01

    Poorly healing diabetic wounds are characterized by diminished collagen production and impaired angiogenesis. HoxD3, a homeobox transcription factor that promotes angiogenesis and collagen synthesis, is up-regulated during normal wound repair whereas its expression is diminished in poorly healing wounds of the genetically diabetic (db/db) mouse. To determine whether restoring expression of HoxD3 would accelerate diabetic wound healing, we devised a novel method of gene transfer, which incorporates HoxD3 plasmid DNA into a methylcellulose film that is placed on wounds created on db/db mice. The HoxD3 transgene was expressed in endothelial cells, fibroblasts, and keratinocytes of the wounds for up to 10 days. More importantly, a single application of HoxD3 to db/db mice resulted in a statistically significant acceleration of wound closure compared to control-treated wounds. Furthermore, we also observed that the HoxD3-mediated improvement in diabetic wound repair was accompanied by increases in mRNA expression of the HoxD3 target genes, Col1A1 and beta 3-integrin leading to enhanced angiogenesis and collagen deposition in the wounds. Although HoxD3-treated wounds also show improved re-epithelialization as compared to control db/db wounds, this effect was not due to direct stimulation of keratinocyte migration by HoxD3. Finally, we show that despite the dramatic increase in collagen synthesis and deposition in HoxD3-treated wounds, these wounds showed normal remodeling and we found no evidence of abnormal wound healing. These results indicate that HoxD3 may provide a means to directly improve collagen deposition, angiogenesis and closure in poorly healing diabetic wounds.

  13. Developmental Vitamin D3 deficiency alters the adult rat brain.

    PubMed

    Féron, F; Burne, T H J; Brown, J; Smith, E; McGrath, J J; Mackay-Sim, A; Eyles, D W

    2005-03-15

    There is growing evidence that Vitamin D(3) (1,25-dihydroxyvitamin D(3)) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D(3) deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The aim of the current study was to examine if there were any permanent outcomes into adulthood when the offspring of Vitamin D(3) deficient dams were restored to a normal diet. The brains of adult rats were examined at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning. Compared to controls animals that were exposed to transient early Vitamin D(3) deficiency had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). We conclude that transient early life hypovitaminosis D(3) not only disrupts brain development but leads to persistent changes in the adult brain. In light of the high incidence of hypovitaminosis D(3) in women of child-bearing age, the public health implications of these findings warrant attention. PMID:15763180

  14. ACC deaminase activity in avirulent Agrobacterium tumefaciens D3.

    PubMed

    Hao, Youai; Charles, Trevor C; Glick, Bernard R

    2011-04-01

    Some plant-growth-promoting bacteria encode the enzyme 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, which breaks down ACC, the direct precursor of ethylene biosynthesis in all higher plants, into ammonia and α-ketobutyrate and, as a result, reduces stress ethylene levels in plants caused by a wide range of biotic and abiotic stresses. It was previously shown that ACC deaminase can inhibit crown gall development induced by Agrobacterium tumefaciens and can partially protect plants from this disease. Agrobacterium tumefaciens D3 has been previously reported to contain a putative ACC deaminase structural gene (acdS) and a regulatory gene (acdR = lrpL). In the present study, it was found that A. tumefaciens D3 is an avirulent strain. ACC deaminase activity and its regulation were also characterized. Under gnotobiotic conditions, wild-type A. tumefaciens D3 was shown to be able to promote plant root elongation, while the acdS and lrpL double mutant strain A. tumefaciens D3-1 lost that ability. When co-inoculated with the virulent strain, A. tumefaciens C58, in wounded castor bean plants, both the wild-type A. tumefaciens D3 and the mutant A. tumefaciens D3-1 were found to be able to significantly inhibit crown gall development induced by A. tumefaciens C58. PMID:21491979

  15. Serum level of vitamin D3 in cutaneous melanoma

    PubMed Central

    de Oliveira, Renato Santos; de Oliveira, Daniel Arcuschin; Martinho, Vitor Augusto Melão; Antoneli, Célia Beatriz Gianotti; Marcussi, Ludmilla Altino de Lima; Ferreira, Carlos Eduardo dos Santos

    2014-01-01

    Objective To compare the level of vitamin D3 in cutaneous melanoma patients, with or without disease activity, with reference values and with patients from a general hospital. Methods The serum levels of vitamin D3 were measured in cutaneous melanoma patients, aged 20 to 88 years, both genders, from January 2010 to December 2013. The samples from the general group were processed at Hospital Israelita Albert Einstein (control group). Data analysis was performed using the Statistics software. Results A total of 100 patients were studied, 54 of them men, with mean age of 54.67 years, and 95 Caucasian. Out of these 100 patients, 17 had active disease. The average levels of vitamin D3 in the melanoma patients were lower than the level considered sufficient, but above the average of the control group. Both groups (with or without active disease) of patients showed a similar distribution of vitamin D3 deficiency. Conclusion Vitamin D3 levels in melanoma patients were higher than those of general patients and lower than the reference level. If the reference values are appropriate, a large part of the population had insufficient levels of vitamin D, including those with melanoma, or else, this standard needs to be reevaluated. No difference in vitamin D3 levels was found among melanoma patients with or without active disease. More comprehensive research is needed to assess the relation between vitamin D and melanoma. PMID:25628199

  16. Induction of the Angiogenic Phenotype by Hox D3

    PubMed Central

    Boudreau, Nancy; Andrews, Catherine; Srebrow, Anabella; Ravanpay, Ali; Cheresh, David A.

    1997-01-01

    Angiogenesis is characterized by distinct phenotypic changes in vascular endothelial cells (EC). Evidence is provided that the Hox D3 homeobox gene mediates conversion of endothelium from the resting to the angiogenic/invasive state. Stimulation of EC with basic fibroblast growth factor (bFGF) resulted in increased expression of Hox D3, integrin αvβ3, and the urokinase plasminogen activator (uPA). Hox D3 antisense blocked the ability of bFGF to induce uPA and integrin αvβ3 expression, yet had no effect on EC cell proliferation or bFGF-mediated cyclin D1 expression. Expression of Hox D3, in the absence of bFGF, resulted in enhanced expression of integrin αvβ3 and uPA. In fact, sustained expression of Hox D3 in vivo on the chick chorioallantoic membrane retained EC in this invasive state and prevented vessel maturation leading to vascular malformations and endotheliomas. Therefore, Hox D3 regulates EC gene expression associated with the invasive stage of angiogenesis. PMID:9314544

  17. Vitamin D3 and cardiovascular function in rats.

    PubMed Central

    Weishaar, R E; Simpson, R U

    1987-01-01

    We have previously identified a receptor for 1,25-dihydroxyvitamin D3 in myocardial cells (Simpson, R.U. 1983. Circulation. 68:239.). To establish the relevance of this observation, we evaluated the role of the prohormone vitamin D3 in regulating cardiovascular function. In rats maintained on a vitamin D3-deficient diet for nine weeks, increases in systolic blood pressure (BP) and serum creatine phosphokinase (CPK) were observed. These increases coincided with a reduction of serum calcium from 10.3 to 5.6 mg/dl. However, while serum calcium remained depressed throughout the study, increases in BP and serum CPK were transient. After nine weeks of vitamin D3-depletion, but not after six weeks, ventricular and vascular muscle contractile function were also markedly enhanced. The increase in ventricular contractile function could not be prevented by maintaining serum calcium at 9.0 mg/dl during the period of D3-depletion. These observations suggest a primary role for the vitamin D3-endocrine system in regulating cardiovascular function. PMID:3034981

  18. Vitamin D3: a helpful immuno-modulator

    PubMed Central

    Di Rosa, Michelino; Malaguarnera, Michele; Nicoletti, Ferdinando; Malaguarnera, Lucia

    2011-01-01

    The active metabolite of vitamin D, 1α, 25-dihydroxyvitamin D3 [1,25(OH)2D3], is involved in calcium and phosphate metabolism and exerts a large number of biological effects. Vitamin D3 inhibits parathyroid hormone secretion, adaptive immunity and cell proliferation, and at the same time promotes insulin secretion, innate immunity and stimulates cellular differentiation. The role of vitamin D3 in immunoregulation has led to the concept of a dual function as both as an important secosteroid hormone for the regulation of body calcium homeostasis and as an essential organic compound that has been shown to have a crucial effect on the immune responses. Altered levels of vitamin D3 have been associated, by recent observational studies, with a higher susceptibility of immune-mediated disorders and inflammatory diseases. This review reports the new developments with specific reference to the metabolic and signalling mechanisms associated with the complex immune-regulatory effects of vitamin D3 on immune cells. PMID:21896008

  19. Predicted 25-hydroxyvitamin D score and incident type 2 diabetes in the Framingham Offspring Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accumulating evidence suggests that vitamin D is involved in the development of type 2 diabetes (T2D). Our objective was to examine the relation between vitamin D status and incidence of T2D. We used a subsample of 1972 Framingham Offspring Study participants to develop a regression model to predict...

  20. Predicted 25-hydroxyvitamin D Score and incident type 2 diabetes in the Framingham Offspring Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accumulating evidence suggests that vitamin D is involved in the development of type 2 diabetes (T2D). Our objective was to examine the relation between vitamin D status and incidence of T2D. We used a subsample of 1972 Framingham Offspring Study participants to develop a regression model to predict...

  1. Levels of 25-hydroxyvitamin D in familial longevity: the Leiden Longevity Study

    PubMed Central

    Noordam, Raymond; de Craen, Anton J.M.; Pedram, Pardis; Maier, Andrea B.; Mooijaart, Simon P.; van Pelt, Johannes; Feskens, Edith J.; Streppel, Martinette T.; Slagboom, P. Eline; Westendorp, Rudi G.J.; Beekman, Marian; van Heemst, Diana

    2012-01-01

    Background: Low levels of 25(OH) vitamin D are associated with various age-related diseases and mortality, but causality has not been determined. We investigated vitamin D levels in the offspring of nonagenarians who had at least one nonagenarian sibling; these offspring have a lower prevalence of age-related diseases and a higher propensity to reach old age compared with their partners. Methods: We assessed anthropometric characteristics, 25(OH) vitamin D levels, parathyroid hormone levels, dietary vitamin D intake and single nucleotide polymorphisms (SNPs) associated with vitamin D levels. We included offspring (n = 1038) of nonagenarians who had at least one nonagenarian sibling, and the offsprings’ partners (n = 461; controls) from the Leiden Longevity Study. We included age, sex, body mass index, month during which blood sampling was performed, dietary and supplemental vitamin D intake, and creatinine levels as possible confounding factors. Results: The offspring had significantly lower levels of vitamin D (64.3 nmol/L) compared with controls (68.4 nmol/L; p = 0.002), independent of possible confounding factors. There was no difference in the levels of parathyroid hormone between groups. Compared with controls, the offspring had a lower frequency of a genetic variant in the CYP2R1 gene (rs2060793) (p = 0.04). The difference in vitamin D levels between offspring and controls persisted over the 2 most prevalent genotypes of this SNP. Interpretation: Compared with controls, the offspring of nonagenarians who had at least one nonagenarian sibling had a reduced frequency of a common variant in the CYP2R1 gene, which predisposes people to high vitamin D levels; they also had lower levels of vitamin D that persisted over the 2 most prevalent genotypes. These results cast doubt on the causal nature of previously reported associations between low levels of vitamin D and age-related diseases and mortality. PMID:23128285

  2. Targeting dietary vitamin D intakes and plasma 25-hydroxyvitamin D in healthy infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin D nutrition has become one of the most widely discussed issues in modern medicine. Ongoing research has challenged traditional views of the role of vitamin D as limited to bone health. A large number of recent studies have raised compelling and as yet unanswered questions about optimal dieta...

  3. Associations between Serum 25-hydroxyvitamin D and Lipids, Lipoprotein Cholesterols, and Homocysteine

    PubMed Central

    Glueck, Charles J.; Jetty, Vybhav; Rothschild, Matan; Duhon, Gregory; Shah, Parth; Prince, Marloe; Lee, Kevin; Goldenberg, Michael; Kumar, Ashwin; Goldenberg, Naila; Wang, Ping

    2016-01-01

    Background: Serum 25(OH) vitamin D levels are inversely associated with cardiovascular disease (CVD) mortality, mediated in part by independent positive relationships with high-density lipoprotein cholesterol (HDLC) and inverse relationships with low-density lipoprotein cholesterol (LDLC), triglyceride, and homocysteine. Aims: In this study, we assessed relationships between fasting serum vitamin D and lipids, lipoprotein cholesterols, and homocysteine. Materials and Methods: We studied 1534 patients sequentially referred to our center from 2007 to 2016. Fasting serum total 25(OH) vitamin D, plasma cholesterol, triglyceride, HDLC, LDLC, and homocysteine were measured. Stepwise regression models were used with total cholesterol, triglyceride, HDLC, LDLC, and homocysteine as dependent variables and explanatory variables age, race, gender, body mass index (BMI), and serum vitamin D levels. Relationships between quintiles of serum vitamin D and triglycerides, HDLC, LDLC, and homocysteine were assessed after covariance adjusting for age, race, gender, and BMI. Results: Fasting serum vitamin D was positively correlated with age, HDLC, and White race, and was inversely correlated with BMI, total and LDL cholesterol, triglyceride, and fasting serum homocysteine (P ≤ 0.0001 for all). Serum vitamin D was a significant independent inverse explanatory variable for total cholesterol, triglyceride, and LDL cholesterol, and accounted for the largest amount of variance in serum total cholesterol (partial R2 =3.6%), triglyceride (partial R2 =3.1%), and LDLC (partial R2 =2.9%) (P < 0.0001 for all). Serum vitamin D was a significant positive explanatory variable for HDLC (partial R2 = 1.4%, P < 0.0001), and a significant inverse explanatory variable for homocysteine (partial R2 = 6.0–12.6%). Conclusions: In hyperlipidemic patients, serum vitamin D was a significant independent inverse determinant of total cholesterol, LDLC, triglyceride, and homocysteine, and a significant independent positive determinant of HDLC. Thus, serum vitamin D might be protective against CVD. PMID:27583236

  4. Maternal 25-hydroxyvitamin D and its association with childhood atopic outcomes and lung function

    PubMed Central

    Wills, A K; Shaheen, S O; Granell, R; Henderson, A J; Fraser, W D; Lawlor, D A

    2013-01-01

    Background It has been suggested that maternal vitamin D status in pregnancy influences the risk of asthma and atopy in the offspring. The epidemiological evidence to support these claims is conflicting and may reflect chance findings and differences in how vitamin D was assessed. Objective To examine the association between blood total maternal 25-hydroxy vitamin D (25(OH)D) concentrations in pregnancy and offspring asthma, atopy and lung function in the largest birth cohort study to date. Methods Participants were largely of white European origin and resident in the South West of England. We examined the associations of maternal 25(OH)D concentrations in pregnancy with the following outcomes in the offspring: wheeze, asthma, atopy, eczema, hayfever, at mean age 7.5 years (n = 3652–4696 depending on outcome), IgE at 7 years (n = 2915) and lung function and bronchial responsiveness at mean age 8.7 years (n = 3728–3784). Results Sixty-eight per cent of mothers had sufficient (> 50 nmol/L) concentrations of 25(OH)D, 27% were insufficient (27.5–49.99 nmol/L) and 5% were deficient (< 27.5 nmol/L). There was no evidence to suggest that maternal 25(OH)D concentration in pregnancy was associated with any respiratory or atopic outcome in the offspring. These findings remained after adjustment for season of measurement and for potential confounders. There was also no evidence that these relationships followed a non-linear form and no evidence that either deficient or high concentrations of maternal 25(OH)D were associated with atopic or respiratory outcomes. Conclusions We found no evidence that maternal blood 25(OH)D concentration in pregnancy is associated with childhood atopic or respiratory outcomes. PMID:24074336

  5. Cardiorespiratory fitness in older adult women: relationships with serum 25-hydroxyvitamin D.

    PubMed

    Ellis, Amy C; Alvarez, Jessica A; Gower, Barbara A; Hunter, Gary R

    2014-12-01

    Previous studies suggest that circulating 25(OH)D may favorably influence cardiorespiratory fitness and fat oxidation. However, these relationships have not been examined in older adult women of different ethnic groups. The objectives of this study were to determine whether serum 25(OH)D is related to cardiovascular fitness (VO2max) in sedentary women ages ≥60 years and to determine whether these associations differ between African Americans (AA) and European Americans (EA). A secondary aim was to determine whether serum 25(OH)D is correlated with respiratory quotient (RQ) during submaximal exercise. This cross-sectional analysis included 67 AA and EA women ages 60-74 years. VO2max was measured by a modified Bruce graded treadmill protocol, and measurements were adjusted for percent fat and lean body mass assessed by air displacement plethysmography. Indirect calorimetry was used to measure RQ at rest and during four submaximal exercise tests. Fasting blood samples were obtained to quantify serum 25(OH)D. Serum 25(OH)D was associated with VO2max (ml/kg LBM/min) independent of percent body fat (r = 0.316, p = 0.010). However, subgroup analysis revealed that this relationship was specific to AA (r = 0.727, p = 0.005 for AA; r = 0.064, p = 0.643 for EA). In all subjects combined, 25(OH)D was inversely correlated (p < 0.01) with all measures of submaximal RQ. Higher serum 25(OH)D was associated with greater cardiorespiratory fitness in older adult AA women. Among both AA and EA, inverse associations between serum 25(OH)D and RQ suggest that women with higher levels of circulating vitamin D also demonstrated greater fat oxidation during submaximal exercise.

  6. 25 Hydroxyvitamin D Deficiency and Its Relationship to Autoimmune Thyroid Disease in the Elderly

    PubMed Central

    Muscogiuri, Giovanna; Mari, Daniela; Prolo, Silvia; Fatti, Letizia M.; Cantone, Maria Celeste; Garagnani, Paolo; Arosio, Beatrice; Di Somma, Carolina; Vitale, Giovanni

    2016-01-01

    Background: Low 25(OH) vitamin D levels have been associated with several autoimmune diseases and recently with autoimmune thyroiditis (AT). The aim of the study was to investigate the association of AT with low 25(OH) vitamin D levels in the elderly. Methods: One hundred sixty-eight elderly subjects (mean age: 81.6 ± 9.4 years) were enrolled. Serum levels of 25(OH) vitamin D, anti-thyroid peroxidase (TPO-Ab), anti-thyroglobulin (TG-Ab) antibodies, free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were measured. Results: The prevalence of AT was significantly higher in subjects with vitamin D deficiency (25(OH) vitamin D < 20 ng/mL) when compared with subjects with normal 25(OH) vitamin D (25(OH) vitamin D ≥ 20 ng/mL) levels (28% vs. 8%, respectively, p = 0.002). Patients with AT and vitamin D deficiency had a comparable hormonal profile compared to patients with AT and vitamin D sufficiency in terms of TSH (p = 0.39), FT3 (p = 0.30), FT4 (p = 0.31), TG-Ab (0.44) and TPO-Ab (0.35). Interestingly, a significant correlation between 25(OH) vitamin D and TPO-Ab (r = −0.27, p = 0.03) and FT3 (r = 0.35, p = 0.006) has been found in subjects with AT while no correlation was found between 25(OH) vitamin D levels and TG-Ab (r = −0.15, p = 0.25), TSH (r = −0.014, p = 0.09) and FT4 (r = 0.13, p = 0.32). Conclusions: These findings suggest that vitamin D deficiency was significantly associated with AT in the elderly. Therefore, the screening for AT should be suggested in subjects with vitamin D deficiency. PMID:27571093

  7. Cardiorespiratory fitness in older adult women: relationships with serum 25-hydroxyvitamin D

    PubMed Central

    Alvarez, Jessica A.; Gower, Barbara A.; Hunter, Gary R.

    2014-01-01

    Previous studies suggest that circulating 25(OH)D may favorably influence cardiorespiratory fitness and fat oxidation. However, these relationships have not been examined in older adult women of different ethnic groups. The objectives of this study were to determine whether serum 25(OH)D is related to cardiovascular fitness (VO2max) in sedentary women ages ≥60 years and to determine whether these associations differ between African Americans (AA) and European Americans (EA). A secondary aim was to determine whether serum 25(OH)D is correlated with respiratory quotient (RQ) during submaximal exercise. This cross-sectional analysis included 67 AA and EA women ages 60–74 years. VO2max was measured by a modified Bruce graded treadmill protocol, and measurements were adjusted for percent fat and lean body mass assessed by air displacement plethysmography. Indirect calorimetry was used to measure RQ at rest and during four submaximal exercise tests. Fasting blood samples were obtained to quantify serum 25(OH)D. Serum 25(OH)D was associated with VO2max (ml/kg LBM/min) independent of percent body fat (r = 0.316, p = 0.010). However, subgroup analysis revealed that this relationship was specific to AA (r = 0.727, p = 0.005 for AA; r = 0.064, p = 0.643 for EA). In all subjects combined, 25(OH)D was inversely correlated (p < 0.01) with all measures of submaximal RQ. Higher serum 25(OH)D was associated with greater cardiorespiratory fitness in older adult AA women. Among both AA and EA, inverse associations between serum 25(OH)D and RQ suggest that women with higher levels of circulating vitamin D also demonstrated greater fat oxidation during submaximal exercise. PMID:24563162

  8. Factors Affecting 25-Hydroxyvitamin D Concentration in Response to Vitamin D Supplementation

    PubMed Central

    Mazahery, Hajar; von Hurst, Pamela R.

    2015-01-01

    Sun exposure is the main source of vitamin D. Due to many lifestyle risk factors vitamin D deficiency/insufficiency is becoming a worldwide health problem. Low 25(OH)D concentration is associated with adverse musculoskeletal and non-musculoskeletal health outcomes. Vitamin D supplementation is currently the best approach to treat deficiency and to maintain adequacy. In response to a given dose of vitamin D, the effect on 25(OH)D concentration differs between individuals, and it is imperative that factors affecting this response be identified. For this review, a comprehensive literature search was conducted to identify those factors and to explore their significance in relation to circulating 25(OH)D response to vitamin D supplementation. The effect of several demographic/biological factors such as baseline 25(OH)D, aging, body mass index(BMI)/body fat percentage, ethnicity, calcium intake, genetics, oestrogen use, dietary fat content and composition, and some diseases and medications has been addressed. Furthermore, strategies employed by researchers or health care providers (type, dose and duration of vitamin D supplementation) and environment (season) are other contributing factors. With the exception of baseline 25(OH)D, BMI/body fat percentage, dose and type of vitamin D, the relative importance of other factors and the mechanisms by which these factors may affect the response remains to be determined. PMID:26121531

  9. 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin D deficiency has potential adverse effects on neurocognitive health and subcortical function. However, no studies have examined the association between vitamin D status, dementia, and cranial magnetic resonance imaging (MRI) indicators of cerebrovascular disease (CVD). Cross-sectional inves...

  10. Automated immunoassays for 25-hydroxyvitamin D (25-OHD): do plasticisers interfere?

    PubMed

    Carter, G D; Jones, J; Ketheeswaran, M; Shannon, J; Singh, B; Kearney, E; Berry, J L

    2015-04-01

    The international quality assessment scheme for vitamin D metabolites (DEQAS) was established in 1989. The scheme involves the quarterly distribution of 5 serum samples prepared from blood collected in plain plastic bags. Following transfer of the donors to a clinic using different bags, sera were found to contain a contaminant that interfered in both the local LC-MS/MS assay and the NIST reference measurement procedure for 25-OHD. It seemed likely that the contaminant was a substance, possibly a plasticiser, leached from the plastic bag. It was subsequently suggested that the unidentified contaminant might also cause interference in certain automated non-extraction assays for 25-OHD. This was investigated in 3 automated immunoassays by comparing serum 25-OHD results from blood collected simultaneously into plain glass tubes and plastic bags. There was no significant difference in results, indicating that the leached substance had no effect on any of the 3 immunoassays examined. PMID:25448742

  11. [Vitamin D, determinant of bone and extrabone health. Importance of vitamin D supplementation in milk and dairy products].

    PubMed

    Navarro Valverde, Cristina; Quesada Gómez, José Manuel

    2015-04-07

    Vitamin D is obtained mainly from ultraviolet irradiation of 7-dehydrocholesterol in the skin to form cholecalciferol (vitamin D3), and minimally from diet, unless vitamin D fortified food is taken, mainly enriched milk. In some countries, vitamin D is added to diet as ergocalciferol (vitamin D2). In the liver, vitamin D3 is hydroxylated to form 25-hydroxyvitamin D3 (marker of body nutritional status of vitamin D). Subsequently, in the kidney, 25OHD3 is hydroxylated to form 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). By VDR stimulation, (1,25)OH)2D3 controls calcium homeostasis and bone health and, what is more, many other cells and tissues including skin, muscle, cardiovascular and immune systems as well as glucose homeostasis. Thus, about 3% of the human genome is regulated by this hormone. Association and recent intervention studies describe beneficial effects on bone, cardiovascular disease, hypertension, diabetes mellitus type 2,colorectal cancer, breast cancer, multiple sclerosis, immune function inflammation etc. A minimum target for public health should be to achieve serum 25OHD levels above 20 ng/ml to ensure optimum status for bone health. However, levels above 30 ng/ml should be reached to achieve other health goals. Paradoxically, inadequacy (or even deficiency) in vitamin D levels is highly prevalent in children and youth in Spain. This deficit persists in adults, as well as in postmenopausal women (osteoporotic or not) and the elderly (especially amongst those institutionalized). Seasonal variation barely normalizes serum 25OHD levels after summer-autumn. Treated postmenopausal osteoporotic women also show high prevalence of inadequate levels of vitamin D, a major contributor to antiresortive treatments failure. A normalization of serum vitamin D enables diet to provide the calcium necessary to achieve a good bone health and an adequate response to antiresortive drugs. Given the difficulty to get adequate levels of vitamin D by UV irradiation and diet, a

  12. Effect of vitamin D3 on lifespan in Caenorhabditis elegans.

    PubMed

    Messing, Jennifer A; Heuberger, Roschelle; Schisa, Jennifer A

    2013-12-01

    Vitamin D is an essential micronutrient, necessary for human health. To determine if Caenorhabditis elegans (C. elegans) could function as an effective model to study the mechanisms of action of vitamin D, we asked if vitamin D3 affects C. elegans lifespan. Multiple factors positively impact lifespan in this system including dietary restriction and vitamin E. In addition, the C. elegans DAF-12 nuclear hormone receptor is homologous to the vitamin D receptor in humans and is therefore a candidate for a functional vitamin D receptor. It was hypothesized that vitamin D3 supplementation would increase the lifespan of C. elegans in a DAF-12-dependent manner. Dose-response curves were completed, and results indicate that exposure to 1,000 µg/ml vitamin D3 significantly increased the lifespan of wild-type worms by up to 39% (p<0.001). The daf-12 mutants exposed to 1,000 µg/ml vitamin D3 lived significantly longer than daf-12 controls exposed to 0 µg/ml (p<0.001), but among worms exposed to 1,000 µg/ml vitamin D3, wild type lived significantly longer than daf-12 (p<0.01). The data suggest that vitamin D3 can interact with multiple receptors, possibly implicating the NHR family of nuclear hormone receptors related to DAF-12. This research is the first to our knowledge to utilize C. elegans as a model to study the impact of vitamin D3 on longevity and supports the use of this model system to increase our understanding of vitamin D function at the cellular level, its role in cellular health, and its potential medicinal utility in humans.

  13. Improvement of maternal vitamin D status with 25-hydroxycholecalciferol positively impacts porcine fetal skeletal muscle development and myoblast activity.

    PubMed

    Hines, E A; Coffey, J D; Starkey, C W; Chung, T K; Starkey, J D

    2013-09-01

    There is little information available regarding the influence of maternal vitamin D status on fetal skeletal muscle development. Therefore, we investigated the effect of improved vitamin D status resulting from 25-hydroxycholecalciferol (25OHD3) supplementation of dams on fetal skeletal muscle developmental characteristics and myoblast activity using Camborough 22 gilts (n = 40) randomly assigned to 1 of 2 corn-soybean meal-based diets. The control diet (CTL) contained 2,500 IU cholecalciferol (D3)/kg diet, whereas the experimental diet contained 500 IU D3/kg diet plus 50 µg 25OHD3/kg diet. Gilts were fed 2.7 kg of their assigned diet once daily beginning 43 d before breeding through d 90 of gestation. On gestational d 90 (± 1), fetal LM and semitendinosus muscle samples were collected for analysis of developmental characteristics and myoblast activity, respectively. No treatment difference was observed in fetal LM cross-sectional area (P = 0.25). Fetuses from 25OHD3-supplemented gilts had more LM fibers (P = 0.04) that tended to be smaller in cross-sectional area compared with CTL fetuses (P = 0.11). A numerical increase in the total number of Pax7+ myoblasts was also observed in fetuses from 25OHD3-supplemented gilts (P = 0.12). Myoblasts derived from the muscles of fetuses from 25OHD3-fed dams displayed an extended proliferative phase in culture compared with those from fetuses of dams fed only D3 (P < 0.0001). The combination of additional muscle fibers and Pax7+ myoblasts with prolonged proliferative capacity could enhance the postnatal skeletal muscle growth potential of fetuses from 25OHD3-supplemented gilts. These data highlight the importance of maternal vitamin D status on the development of fetal skeletal muscle.

  14. Impairment of cytokine production in mice fed a vitamin D3-deficient diet.

    PubMed Central

    Kankova, M; Luini, W; Pedrazzoni, M; Riganti, F; Sironi, M; Bottazzi, B; Mantovani, A; Vecchi, A

    1991-01-01

    C57Bl/6 female mice fed a Vitamin D (VIT-D)-deficient diet had serum levels of 25-hydroxyvitamin D decreasing with the time of diet exposure (3 and 8 weeks). Cytokine production (IL-6, TNF and IL-1) by peritoneal macrophages cultured in vitro with a standard stimulus, LPS, evaluated in the supernatants as biological activity, was significantly reduced in VIT-D-deficient animals. The defect in monokine production was partial and was evident at suboptimal LPS concentrations and incubation times. I-A antigen expression, induced in macrophages by in vitro exposure to IFN-gamma, was not modified in VIT-D-deficient mice, but IFN-gamma-inducible macrophage cytotoxicity to tumour target cells was significantly decreased in VIT-D-deficient animals. Moreover, basal and Poly I:C-induced NK activity was not modified by VIT-D deficiency. Thus, macrophage functions, such as cytokine production and tumour cytotoxicity induction, are down-modulated in vitro by VIT-D deprivation. To give more support to the relevance of VIT-D availability for cytokine production, TNF and IL-6 have been evaluated in the sera of control and VIT-D-deficient mice given LPS as a model stimulus. Serum peak levels of both cytokines were at least halved in VIT-D-deprived mice. Thus, VIT-D deficiency may represent a model of partial defect of monokine production. PMID:1655638

  15. D3-Brane Model Building and the Supertrace Rule.

    PubMed

    Bena, Iosif; Graña, Mariana; Kuperstein, Stanislav; Ntokos, Praxitelis; Petrini, Michela

    2016-04-01

    A common way to obtain standard-model-like Lagrangians in string theory is to place D3-branes inside flux compactifications. The bosonic and fermionic masses and couplings of the resulting gauge theory are determined by the ten-dimensional metric and the fluxes, respectively, and the breaking of supersymmetry is soft. However, not any soft-supersymmetry-breaking Lagrangian can be obtained this way since the string theory equations of motion impose certain relations between the soft couplings. We show that for D3-branes in background fluxes, these relations imply that the sums of the squares of the boson and of the fermion masses are equal and that, furthermore, one- and two-loop quantum corrections do not spoil this equality. This makes the use of D3-branes for constructing computationally controllable models for physics beyond the standard model problematic. PMID:27104696

  16. D3-Brane Model Building and the Supertrace Rule.

    PubMed

    Bena, Iosif; Graña, Mariana; Kuperstein, Stanislav; Ntokos, Praxitelis; Petrini, Michela

    2016-04-01

    A common way to obtain standard-model-like Lagrangians in string theory is to place D3-branes inside flux compactifications. The bosonic and fermionic masses and couplings of the resulting gauge theory are determined by the ten-dimensional metric and the fluxes, respectively, and the breaking of supersymmetry is soft. However, not any soft-supersymmetry-breaking Lagrangian can be obtained this way since the string theory equations of motion impose certain relations between the soft couplings. We show that for D3-branes in background fluxes, these relations imply that the sums of the squares of the boson and of the fermion masses are equal and that, furthermore, one- and two-loop quantum corrections do not spoil this equality. This makes the use of D3-branes for constructing computationally controllable models for physics beyond the standard model problematic.

  17. Taming supersymmetric defects in 3d-3d correspondence

    NASA Astrophysics Data System (ADS)

    Gang, Dongmin; Kim, Nakwoo; Romo, Mauricio; Yamazaki, Masahito

    2016-07-01

    We study knots in 3d Chern-Simons theory with complex gauge group {SL}(N,{{C}}), in the context of its relation with 3d { N }=2 theory (the so-called 3d-3d correspondence). The defect has either co-dimension 2 or co-dimension 4 inside the 6d (2,0) theory, which is compactified on a 3-manifold \\hat{M}. We identify such defects in various corners of the 3d-3d correspondence, namely in 3d {SL}(N,{{C}}) CS theory, in 3d { N }=2 theory, in 5d { N }=2 super Yang-Mills theory, and in the M-theory holographic dual. We can make quantitative checks of the 3d-3d correspondence by computing partition functions at each of these theories. This Letter is a companion to a longer paper [1], which contains more details and more results.

  18. Vitamin D(3) receptor ablation alters mammary gland morphogenesis.

    PubMed

    Zinser, Glendon; Packman, Kathryn; Welsh, JoEllen

    2002-07-01

    Postnatal mammary gland morphogenesis is achieved through coordination of signaling networks in both the epithelial and stromal cells of the developing gland. While the major proliferative hormones driving pubertal mammary gland development are estrogen and progesterone, studies in transgenic and knockout mice have successfully identified other steroid and peptide hormones that impact on mammary gland development. The vitamin D(3) receptor (VDR), whose ligand 1,25-dihydroxyvitamin D(3) is the biologically active form of vitamin D(3), has been implicated in control of differentiation, cell cycle and apoptosis of mammary cells in culture, but little is known about the physiological relevance of the vitamin D(3) endocrine system in the developing gland. In these studies, we report the expression of the VDR in epithelial cells of the terminal end bud and subtending ducts, in stromal cells and in a subset of lymphocytes within the lymph node. In the terminal end bud, a distinct gradient of VDR expression is observed, with weak VDR staining in proliferative populations and strong VDR staining in differentiated populations. The role of the VDR in ductal morphogenesis was examined in Vdr knockout mice fed high dietary Ca(2+) which normalizes fertility, serum estrogen and neonatal growth. Our results indicate that mammary glands from virgin Vdr knockout mice are heavier and exhibit enhanced growth, as evidenced by higher numbers of terminal end buds, greater ductal outgrowth and enhanced secondary branch points, compared with glands from age- and weight-matched wild-type mice. In addition, glands from Vdr knockout mice exhibit enhanced growth in response to exogenous estrogen and progesterone, both in vivo and in organ culture, compared with glands from wild-type mice. Our data provide the first in vivo evidence that 1,25-dihydroxyvitamin D(3) and the VDR impact on ductal elongation and branching morphogenesis during pubertal development of the mammary gland. Collectively

  19. The Kinetics of Vitamin D3 in the Osteoblastic Cell

    PubMed Central

    Buchanan, James L; Gilbert, Robert; Ou, Yvonne; Nohe, Anja; Schaefer, Rachel

    2014-01-01

    Experimental evidience is presented on the translocation of vitamin D metabolite, 1,25-(OH)2D3, from the membrane to the nucleus in osteoblast progenitor cells. A mathematical model permitting traversal of the cytoplasm at either a fixed velocity or by diffusion is formulated in order to determine whether transport along the cytoskeletal tracks is more consistent with the observed spatial-temporal distribution than diffusion, and it is so found. The model includes reactions in the nucleus involving D3 to form other compounds, such as protegerin, and thus also makes predictions of the concentrations of these compounds in various regions of the cell. PMID:23775045

  20. Ghost-Free, Finite, Fourth-Order D=3 Gravity

    NASA Astrophysics Data System (ADS)

    Deser, S.

    2009-09-01

    Canonical analysis of a recently proposed linear+quadratic curvature gravity model in D=3 establishes its pure, irreducibly fourth derivative, quadratic curvature limit as both ghost-free and power-counting UV finite, thereby maximally violating standard folklore. This limit is representative of a generic class whose kinetic terms are conformally invariant in any dimension, but it is unique in simultaneously avoiding the transverse-traceless graviton ghosts plaguing D>3 quadratic actions as well as double pole propagators in its other variables. While the two-term model is also unitary, its additional mode’s second-derivative nature forfeits finiteness.

  1. Evaluation of the efficacy of vitamin D3 or its metabolites on thiram-induced tibial dyschondroplasia in chickens.

    PubMed

    Rath, N C; Kannan, L; Pillai, P B; Huff, W E; Huff, G R; Horst, R L; Emmert, J L

    2007-10-01

    Two trials were conducted to determine if thiram-induced tibial dyschondroplasia (TD) in chickens was linked to a vitamin D deficiency and calcium homeostasis dysregulation, and whether feeding vitamin D fortified diets may prevent it. Day-old chickens were given grower diets containing different vitamin D products throughout the experiment until necropsy on day 16. Half of the birds in each feed group received thiram at levels of 100 ppm (trial 1) or 50 ppm (trial 2) between days 7-9 to induce TD. The birds were weighed, bled, and euthanized to determine TD incidences and severity by examining the growth plates. Tibial bones were used to measure biomechanical strength and ash content. Blood concentrations of 25-hydroxyvitamin D, Ca, P, alkaline phosphatase, and creatine kinase were measured in serum that showed no differences between different groups. Thiram reduced body weight and induced TD regardless of any vitamin D treatment to the same extent as untreated birds.

  2. 21 CFR 172.380 - Vitamin D3.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the... crystallization. (b) Vitamin D3 meets the specifications of the Food Chemicals Codex, 5th ed. (2004), pp....

  3. 21 CFR 172.380 - Vitamin D 3;.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the... crystallization. (b) Vitamin D3 meets the specifications of the Food Chemicals Codex, 5th ed. (2004), pp....

  4. 21 CFR 172.380 - Vitamin D 3.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the United States Pharmacopeial.../federal-register/cfr/ibr-locations.html. (c) The additive may be used as follows: (1) At levels not to...-dehydrocholesterol produced from cholesterol and is purified by crystallization. (b) Vitamin D3 meets...

  5. 21 CFR 172.380 - Vitamin D3.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the... crystallization. (b) Vitamin D3 meets the specifications of the Food Chemicals Codex, 5th ed. (2004), pp....

  6. 21 CFR 172.380 - Vitamin D3.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the... crystallization. (b) Vitamin D3 meets the specifications of the Food Chemicals Codex, 5th ed. (2004), pp....

  7. Quantum Electrodynamics in d=3 from the ε Expansion.

    PubMed

    Di Pietro, Lorenzo; Komargodski, Zohar; Shamir, Itamar; Stamou, Emmanuel

    2016-04-01

    We study quantum electrodynamics in d=3 coupled to N_{f} flavors of fermions. The theory flows to an IR fixed point for N_{f} larger than some critical number N_{f}^{c}. For N_{f}≤N_{f}^{c}, chiral-symmetry breaking is believed to take place. In analogy with the Wilson-Fisher description of the critical O(N) models in d=3, we make use of the existence of a fixed point in d=4-2ε to study the three-dimensional conformal theory. We compute, in perturbation theory, the IR dimensions of fermion bilinear and quadrilinear operators. For small N_{f}, a quadrilinear operator can become relevant in the IR and destabilize the fixed point. Therefore, the epsilon expansion can be used to estimate N_{f}^{c}. An interesting novelty compared to the O(N) models is that the theory in d=3 has an enhanced symmetry due to the structure of 3D spinors. We identify the operators in d=4-2ε that correspond to the additional conserved currents at d=3 and compute their infrared dimensions. PMID:27081967

  8. Quantum Electrodynamics in d=3 from the ε Expansion.

    PubMed

    Di Pietro, Lorenzo; Komargodski, Zohar; Shamir, Itamar; Stamou, Emmanuel

    2016-04-01

    We study quantum electrodynamics in d=3 coupled to N_{f} flavors of fermions. The theory flows to an IR fixed point for N_{f} larger than some critical number N_{f}^{c}. For N_{f}≤N_{f}^{c}, chiral-symmetry breaking is believed to take place. In analogy with the Wilson-Fisher description of the critical O(N) models in d=3, we make use of the existence of a fixed point in d=4-2ε to study the three-dimensional conformal theory. We compute, in perturbation theory, the IR dimensions of fermion bilinear and quadrilinear operators. For small N_{f}, a quadrilinear operator can become relevant in the IR and destabilize the fixed point. Therefore, the epsilon expansion can be used to estimate N_{f}^{c}. An interesting novelty compared to the O(N) models is that the theory in d=3 has an enhanced symmetry due to the structure of 3D spinors. We identify the operators in d=4-2ε that correspond to the additional conserved currents at d=3 and compute their infrared dimensions.

  9. A liposomal model that mimics the cutaneous production of vitamin D3. Studies of the mechanism of the membrane-enhanced thermal isomerization of previtamin D3 to vitamin D3

    NASA Technical Reports Server (NTRS)

    Tian, X. Q.; Holick, M. F.

    1999-01-01

    We reported previously that the rate of previtamin D3 (preD3) <==> vitamin D3 isomerization was enhanced by about 10 times in the skin compared with that in organic solvents. To elucidate the mechanism by which the rate of this reaction is enhanced in the skin, we developed a liposomal model that mimicked the enhanced isomerization of preD3 to vitamin D3 that was described in human skin. Using this model we studied the effect of changing the polarity of preD3 as well as changing the chain length and the degree of saturation of liposomal phospholipids on the kinetics of preD3 <==> vitamin D3 isomerization. We found that a decrease in the hydrophilic interaction of the preD3 with liposomal phospholipids by an esterification of the 3beta-hydroxy of preD3 (previtamin D3-3beta-acetate) reduced the rate of the isomerization by 67%. The addition of a hydroxyl on C-25 of the hydrophobic side chain (25-hydroxyprevitamin D3), which decreased the hydrophobic interaction of preD3 with the phospholipids, reduced the rate by 87%. In contrast, in an isotropic n-hexane solution, there was little difference among the rates of the conversion of preD3, its 3beta-acetate, and 25-hydroxy derivatives to their corresponding vitamin D3 compounds. We also determined rate constants (k) of preD3 <==> vitamin D3 isomerization in liposomes containing phosphatidylcholines with different carbon chain lengths. The rates of the reaction were found to be enhanced as the number of carbons (Cn) in the hydrocarbon chain of the phospholipids increased from 10 to 18. In conclusion, these results support our hypothesis that amphipathic interactions between preD3 and membrane phospholipids stabilize preD3 in its "cholesterol like" cZc-conformer, the only conformer of preD3 that can convert to vitamin D3. The stronger these interactions were, the more preD3 was likely in its cZc conformation at any moment and the faster was the rate of its conversion to vitamin D3.

  10. Swiss-cheese D3- D7 soft SUSY breaking

    NASA Astrophysics Data System (ADS)

    Misra, Aalok; Shukla, Pramod

    2010-03-01

    We address issues related to (i) a proposal for resolving a long-standing tension between large volume cosmology and phenomenology as regards reconciliation of requirements of different gravitino masses within the same string-theoretic framework, as well as (ii) evaluation of soft supersymmetry breaking terms and open-string moduli masses in the context of type IIB large volume compactifications involving orientifolds of the Swiss-cheese Calabi-Yau WCP[1,1,1,6,9] with a single mobile space-time filling D3-brane and stacks of D7-branes wrapping the "big" divisor Σ as well as supporting D7-brane fluxes. In addition, we also include perturbative α-corrections and non-perturbative world-sheet instanton corrections to the Kähler potential as well as Euclidean D3-instanton superpotential. First, using the toric data for the aforementioned Swiss-cheese Calabi-Yau and GLSM techniques, we obtain in the large volume limit, the geometric Kähler potential for the big (and small) divisor(s) in terms of derivatives of genus-two Siegel theta functions. Next, we show that as the mobile space-time filling D3-brane moves from a particular non-singular elliptic curve embedded in the Swiss-cheese Calabi-Yau to another non-singular elliptic curve, it is possible to obtain 10 12 GeV gravitino during the primordial inflationary era as well as, e.g., a TeV gravitino in the present era, within the same set up for the same volume of the Calabi-Yau stabilized at around 10ls6. Then by constructing local (i.e. localized around the location of the mobile D3-brane in the Calabi-Yau) appropriate involutively-odd harmonic one-form on the big divisor that lies in coker(H∂¯,-(0,1)(CY)→iH∂¯,-(0,1)(Σ)) and extremizing the potential, we show that it is possible to obtain an O(1)g from the wrapping of D7-branes on the big divisor due to competing contributions from the Wilson line moduli relative to the divisor volume modulus. To permit gaugino condensation, we take the rigid limit of the

  11. Nonperturbative gluon and ghost propagators in d = 3

    SciTech Connect

    Papavassiliou, Joannis

    2011-05-23

    We study the nonperturbative gluon and ghost propagators in d = 3 Yang-Mills, using the Schwinger-Dyson equations of the pinch technique. The use of the Schwinger mechanism leads to the dynamical generation of a gluon mass, which, in turn, gives rise to an infrared finite gluon propagator and ghost dressing function. The propagators obtained are in very good agreement with the results of SU(2) lattice simulations.

  12. Role of the D3 dopamine receptor in nicotine sensitization.

    PubMed

    Smith, Laura N; Bachus, Susan E; McDonald, Craig G; Smith, Robert F

    2015-08-01

    Adolescent cigarette use is associated with reduced quitting success and continued smoking in adulthood. Interestingly, polymorphisms of the dopamine D3 receptor (DRD3) gene have been associated with smoking behavior, and the receptor is expressed in an age- and brain region-dependent manner that suggests relevance to addiction. Here, we investigate the possible role of dopamine-related receptors, including DRD3 and an intriguing splice variant known as D3nf, in nicotine-induced sensitization. In adolescent and adult male rats, we examined (1) alterations occurring in dopamine receptor-related mRNAs (DRD1, DRD2, DRD3 and D3nf) at two time points during a sensitizing regimen of nicotine and (2) whether DRD3 antagonism either during the initial treatment (induction) or at a later challenge exposure (expression) is able to block nicotine sensitization. Nicotine-induced changes were seen for DRD3 and D3nf mRNAs in the nucleus accumbens shell early in repeated exposure in both age groups. DRD3 antagonism only blocked the induction of sensitization in adolescents and did not block the expression of sensitization in either age group. Adolescents and adults showed opposite DRD1 mRNA responses to nicotine treatment, while no age- and nicotine-related changes in DRD2 mRNA were observed. These data reveal important age-dependent regulation of DRD1- and DRD3-related mRNAs during the course of nicotine exposure. Furthermore, they highlight a requirement for DRD3 signaling in the development of adolescent nicotine sensitization, suggesting it may represent an appropriate target in the prevention of nicotine dependence initiated at this age.

  13. A simultaneous 2D/3D autostereo workstation

    NASA Astrophysics Data System (ADS)

    Chau, Dennis; McGinnis, Bradley; Talandis, Jonas; Leigh, Jason; Peterka, Tom; Knoll, Aaron; Sumer, Aslihan; Papka, Michael; Jellinek, Julius

    2012-03-01

    We present a novel immersive workstation environment that scientists can use for 3D data exploration and as their everyday 2D computer monitor. Our implementation is based on an autostereoscopic dynamic parallax barrier 2D/3D display, interactive input devices, and a software infrastructure that allows client/server software modules to couple the workstation to scientists' visualization applications. This paper describes the hardware construction and calibration, software components, and a demonstration of our system in nanoscale materials science exploration.

  14. Dopamine D2/D3 receptor availability and venturesomeness.

    PubMed

    Bernow, Nina; Yakushev, Igor; Landvogt, Christian; Buchholz, Hans-Georg; Smolka, Michael N; Bartenstein, Peter; Lieb, Klaus; Gründer, Gerhard; Vernaleken, Ingo; Schreckenberger, Mathias; Fehr, Christoph

    2011-08-30

    The construct of impulsivity is considered as a major trait of personality. There is growing evidence that the mesolimbic dopamine system plays an important role in the modulation of impulsivity and venturesomeness, the two key components within the impulsivity-construct. The aim of the present study was to explore an association between trait impulsivity measured with self-assessment and the dopaminergic neurotransmission as measured by positron emission tomography (PET) in a cohort of healthy male subjects. In vivo D2/D3 receptor availability was determined with [(18)F]fallypride PET in 18 non-smoking healthy subjects. The character trait impulsivity was measured using the Impulsiveness-Venturesomeness-Empathy questionnaire (I7). Image processing and statistical analysis was performed on a voxel-by-voxel basis using statistical parametric mapping (SPM) software. The I7 subscale venturesomeness correlated positively with the D2/D3 receptor availability within the left temporal cortex and the thalamus. Measures on the I7 subscale impulsiveness and empathy did not correlate with the D2/D3 receptor availability in any brain region investigated. Our results suggest the involvement of extrastriatal dopaminergic neurotransmission in venturesomeness, a component of impulsivity. PMID:21689908

  15. Metabolism of 20-Hydroxyvitamin D3 and 20,23-Dihydroxyvitamin D3 by Rat and Human CYP24A1

    PubMed Central

    Tieu, Elaine W.; Li, Wei; Chen, Jianjun; Kim, Tae-Kang; Ma, Dejian; Slominski, Andrzej T.; Tuckey, Robert C.

    2015-01-01

    CYP11A1 hydroxylates vitamin D3 producing 20S-hydroxyvitamin D3 [20(OH)D3] and 20S,23-dihydroxyvitamin D3 [20,23(OH)2D3] as the major and most characterized metabolites. Both display immuno-regulatory and anti-cancer properties while being non-calcemic. A previous study indicated 20(OH)D3 can be metabolized by rat CYP24A1 to products including 20S,24-dihydroxyvitamin D3 [20,24(OH)2D3] and 20S,25-dihydroxyvitamin D3, with both producing greater inhibition of melanoma colony formation than 20(OH)D3. The aim of this study was to characterize the ability of rat and human CYP24A1 to metabolize 20(OH)D3 and 20,23(OH)2D3. Both isoforms metabolized 20(OH)D3 to the same dihydroxyvitamin D species with no secondary metabolites being observed. Hydroxylation at C24 produced both enantiomers of 20,24(OH)2D3. For rat CYP24A1 the preferred initial site of hydroxylation was at C24 whereas the human enzyme preferred C25. 20,23(OH)2D3 was initially metabolized to 20S,23,24-trihydroxyvitamin D3 and 20S,23,25-trihydroxyvitamin D3 by rat and human CYP24A1 as determined by NMR, with both isoforms showing a preference for initial hydroxylation at C25. CYP24A1 was able to further oxidize these metabolites in a series of reactions which included the cleavage of C23-C24 bond, as indicated by high resolution mass spectrometry of the products, analogous to the catabolism of 1,25(OH)2D3 via the C24-oxidation pathway. Similar catalytic efficiencies were observed for the metabolism of 20(OH)D3 and 20,23(OH)2D3 by human CYP24A1 and were lower than for the metabolism of 1,25(OH)2D3. We conclude that rat and human CYP24A1 metabolizes 20(OH)D3 producing only dihydroxyvitamin D3 species as products which retain biological activity, whereas 20,23(OH)2D3 undergoes multiple oxidations which include cleavage of the side chain. PMID:25727742

  16. Effect of vitamin D status improvement with 25-hydroxycholecalciferol on skeletal muscle growth characteristics and satellite cell activity in broiler chickens.

    PubMed

    Hutton, K C; Vaughn, M A; Litta, G; Turner, B J; Starkey, J D

    2014-08-01

    Skeletal muscle satellite cells (SC) play a critical role in the hypertrophic growth of postnatal muscle. Increases in breast meat yield have been consistently observed in broiler chickens fed 25-hydroxycholecalciferol (25OHD3), but it is unclear whether this effect is mediated by SC. Thus, our objective was to determine the effect of vitamin D status improvement by replacing the majority of dietary vitamin D3 (D3) with 25OHD3 on SC activity and muscle growth characteristics in the pectoralis major (PM) and the biceps femoris (BF) muscles. Day-old, male Ross 708 broiler chickens (n = 150) were fed 1 of 2 corn and soybean meal-based diets for 49 d. The control diet (CTL) contained 5,000 IU D3 per kg of diet and the experimental diet (25OHD3) contained 2,240 IU D3 per kg of diet + 2,760 IU 25OHD3 per kg of diet. Ten birds per treatment were harvested every 7 d. Two hours before harvest, birds were injected intraperitoneally with 5'-bromo-2'deoxyuridine (BrdU) to label mitotically active cells. Blood was collected from each bird at harvest to measure circulating concentrations of 25OHD3, a marker of vitamin D status. The PM and BF muscles were weighed and processed for cryohistological determination of skeletal muscle fiber cross-sectional area, enumeration of Myf-5+ and Pax7+ SC, and mitotically active (BrdU+) SC using immunofluorescence microscopy. Circulating 25OHD3 concentrations were greater in 25OHD3-fed birds on d 7, 14, 21, 28, 35, 42, and 49 when compared with CTL (P < 0.001). Growth performance and feed efficiency did not differ among dietary treatments (P > 0.10). Improved vitamin D status as a result of feeding 25OHD3 increased the number of mitotically active (Pax7+;BrdU+) SC (P = 0.01) and tended to increase the density of Pax7+ SC (P = 0.07) in the PM muscles of broilers on d 21 and 35, respectively. Broiler chickens fed 25OHD3 also tended to have greater Myf-5+ SC density (P = 0.09) on d 14, greater total nuclear density (P = 0.05) on d 28, and a

  17. Recent update of the RPLUS2D/3D codes

    NASA Technical Reports Server (NTRS)

    Tsai, Y.-L. Peter

    1991-01-01

    The development of the RPLUS2D/3D codes is summarized. These codes utilize LU algorithms to solve chemical non-equilibrium flows in a body-fitted coordinate system. The motivation behind the development of these codes is the need to numerically predict chemical non-equilibrium flows for the National AeroSpace Plane Program. Recent improvements include vectorization method, blocking algorithms for geometric flexibility, out-of-core storage for large-size problems, and an LU-SW/UP combination for CPU-time efficiency and solution quality.

  18. Recombination of H(3+) and D(3+) ions with electrons

    NASA Technical Reports Server (NTRS)

    Johnsen, R.; Gougousi, T.; Golde, M. F.

    1994-01-01

    Flowing-afterglow measurements in decaying H3(+) or D3(+) plasmas suggest that de-ionization does not occur by simple binary recombination of a single ion species. We find that vibrational excitation of the ions fails to provide an explanation for the effect, contrary to an earlier suggestion. Instead, we suggest that collisional stabilization of H3** Rydberg molecules by ambient electrons introduces an additional dependence on electron density. The proposed mechanism would permit plasma de-ionization to occur without the need for dissociative recombination by the mechanism of potential-surface crossings.

  19. 78 FR 77384 - DSM Nutritional Products; Filing of Food Additive Petition (Animal Use)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-23

    ... in vitamin D formulations, including 25-hydroxyvitamin D 3 , used in animal food. DATES: Submit... for the safe use of ethoxyquin as a chemical preservative in vitamin D formulations, including...

  20. Vitamin D Test

    MedlinePlus

    ... limited. Home Visit Global Sites Search Help? Vitamin D Tests Share this page: Was this page helpful? Also known as: Ergocalciferol (Vitamin D 2 ); Cholecalciferol (Vitamin D 3 ); Calcidiol (25-hydroxyvitamin ...

  1. 750 GeV diphotons from a D3-brane

    NASA Astrophysics Data System (ADS)

    Heckman, Jonathan J.

    2016-05-01

    Motivated by the recently reported diphoton excess at 750 GeV observed by both CMS and ATLAS, we study string-based particle physics models which can accommodate this signal. Quite remarkably, although Grand Unified Theories in F-theory tend to impose tight restrictions on candidate extra sectors, the case of a probe D3-brane near an E-type Yukawa point naturally leads to a class of strongly coupled models capable of accommodating the observed signature. In these models, the visible sector is realized by intersecting 7-branes, and the 750 GeV resonance is a scalar modulus associated with motion of the D3-brane in the direction transverse to the Standard Model 7-branes. Integrating out heavy 3-7 string messenger states leads to dimension five operators for gluon fusion production and diphoton decays. Due to the unified structure of interactions, these models also predict that there should be additional decay channels to ZZ and Zγ. We also comment on models with distorted unification, where both the production mechanism and decay channels can differ.

  2. The dopamine D3 receptor gene and posttraumatic stress disorder.

    PubMed

    Wolf, Erika J; Mitchell, Karen S; Logue, Mark W; Baldwin, Clinton T; Reardon, Annemarie F; Aiello, Alison; Galea, Sandro; Koenen, Karestan C; Uddin, Monica; Wildman, Derek; Miller, Mark W

    2014-08-01

    The dopamine D3 receptor (DRD3) gene has been implicated in schizophrenia, autism, and substance use-disorders and is related to emotion reactivity, executive functioning, and stress-responding, processes impaired in posttraumatic stress disorder (PTSD). The aim of this candidate gene study was to evaluate DRD3 polymorphisms for association with PTSD. The discovery sample was trauma-exposed White, non-Hispanic U.S. veterans and their trauma-exposed intimate partners (N = 491); 60.3% met criteria for lifetime PTSD. The replication sample was 601 trauma-exposed African American participants living in Detroit, Michigan; 23.6% met criteria for lifetime PTSD. Genotyping was based on high-density bead chips. In the discovery sample, 4 single nucleotide polymorphisms (SNPs), rs2134655, rs201252087, rs4646996, and rs9868039, showed evidence of association with PTSD and withstood correction for multiple testing. The minor alleles were associated with reduced risk for PTSD (OR range = 0.59 to 0.69). In the replication sample, rs2251177, located 149 base pairs away from the most significant SNP in the discovery sample, was nominally associated with PTSD in men (OR = 0.32). Although the precise role of the D3 receptor in PTSD is not yet known, its role in executive functioning and emotional reactivity, and the sensitivity of the dopamine system to environmental stressors could potentially explain this association. PMID:25158632

  3. The Dopamine D3 Receptor Gene and Posttraumatic Stress Disorder

    PubMed Central

    Wolf, Erika J.; Mitchell, Karen S.; Logue, Mark W.; Baldwin, Clinton T.; Reardon, Annemarie F.; Aiello, Alison; Galea, Sandro; Koenen, Karestan C.; Uddin, Monica; Wildman, Derek; Miller, Mark W.

    2014-01-01

    The dopamine D3 receptor (DRD3) gene has been implicated in schizophrenia, autism, and substance use-disorders and is related to emotion reactivity, executive functioning, and stress-responding, processes impaired in posttraumatic stress disorder (PTSD). This aim of this candidate gene study was to evaluate DRD3 polymorphisms for association with PTSD. The discovery sample was trauma-exposed white, non-Hispanic veterans and their trauma-exposed intimate partners (N = 491); 60% met criteria for lifetime PTSD. The replication sample was 601 trauma-exposed African American participants; 24% met criteria for lifetime PTSD. Genotyping was based on high-density bead chips. In the discovery sample, four single nucleotide polymorphisms (SNPs), rs2134655, rs201252087, rs4646996, and rs9868039, showed evidence of association with PTSD and withstood correction for multiple testing. The minor alleles were associated with reduced risk for PTSD (odds ratio range: 0.59 – 0.69). In the replication sample, rs2251177, located 149 base pairs away from the most significant SNP in the discovery sample, was nominally associated with PTSD in men (odds ratio: 0.32). Although the precise role of the D3 receptor in PTSD is not yet known, its role in executive functioning and emotional reactivity, and the sensitivity of the dopamine system to environmental stressors, could potentially explain this association. PMID:25158632

  4. 16 CFR Appendix D3 to Part 305 - Water Heaters-Oil

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Water Heaters-Oil D3 Appendix D3 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS ENERGY AND WATER... RULEâ) Pt. 305, App. D3 Appendix D3 to Part 305—Water Heaters—Oil Range Information Capacity First...

  5. Interactive initialization of 2D/3D rigid registration

    SciTech Connect

    Gong, Ren Hui; Güler, Özgür; Kürklüoglu, Mustafa; Lovejoy, John; Yaniv, Ziv

    2013-12-15

    Purpose: Registration is one of the key technical components in an image-guided navigation system. A large number of 2D/3D registration algorithms have been previously proposed, but have not been able to transition into clinical practice. The authors identify the primary reason for the lack of adoption with the prerequisite for a sufficiently accurate initial transformation, mean target registration error of about 10 mm or less. In this paper, the authors present two interactive initialization approaches that provide the desired accuracy for x-ray/MR and x-ray/CT registration in the operating room setting. Methods: The authors have developed two interactive registration methods based on visual alignment of a preoperative image, MR, or CT to intraoperative x-rays. In the first approach, the operator uses a gesture based interface to align a volume rendering of the preoperative image to multiple x-rays. The second approach uses a tracked tool available as part of a navigation system. Preoperatively, a virtual replica of the tool is positioned next to the anatomical structures visible in the volumetric data. Intraoperatively, the physical tool is positioned in a similar manner and subsequently used to align a volume rendering to the x-ray images using an augmented reality (AR) approach. Both methods were assessed using three publicly available reference data sets for 2D/3D registration evaluation. Results: In the authors' experiments, the authors show that for x-ray/MR registration, the gesture based method resulted in a mean target registration error (mTRE) of 9.3 ± 5.0 mm with an average interaction time of 146.3 ± 73.0 s, and the AR-based method had mTREs of 7.2 ± 3.2 mm with interaction times of 44 ± 32 s. For x-ray/CT registration, the gesture based method resulted in a mTRE of 7.4 ± 5.0 mm with an average interaction time of 132.1 ± 66.4 s, and the AR-based method had mTREs of 8.3 ± 5.0 mm with interaction times of 58 ± 52 s. Conclusions: Based on the

  6. "big" Divisor D3/D7 Swiss-Cheese Phenomenology

    NASA Astrophysics Data System (ADS)

    Misra, Aalok

    We review progress made over the past couple of years in the field of Swiss-Cheese Phenomenology involving a mobile spacetime filling D3-brane and stack(s) of fluxed D7-branes wrapping the "big" (as opposed to the "small") divisor in (the orientifold of (a) Swiss-Cheese Calabi-Yau. The topics reviewed include reconciliation of large volume cosmology and phenomenology, evaluation of soft supersymmetry breaking parameters, one-loop RG-flow equations' solutions for scalar masses, obtaining fermionic (possibly first two generations' quarks/leptons) mass scales in the {O}(MeV--GeV)-regime as well as (first two generations') neutrino masses (and their one-loop RG flow) of around an eV. The heavy sparticles and the light fermions indicate the possibility of "split SUSY" large volume scenario.

  7. Wear and friction behavior of Zr implanted D3 steel

    SciTech Connect

    Akbas, N.; Saklakoglu, I.E.; Monteiro, O.R.; Brown, I.G.

    2001-08-23

    Multicharged, pure, high current and pulsed ion beams of Zr have been extracted from a metal vapor vacuum arc (MEVVA) source and implanted into AISI D3 (C: 2-2,35%, Mn: 0,60%, Si: 0,60%, Cr: 11-13,50%, Ni: 0,30%, W: 1%, V: 1%) tool steel samples at the 3,6.1016, 5.1016 and 1.1017 ions/cm2 doses. The wear resistance and friction coefficient have been estimated using pin-on-disc wear tests. Implantation of Zr decreased the wear loss and friction coefficient. RBS, AES and SEM Microprobe analyses were used as a guide for explanation of implantation's effects.

  8. Modulation of 1alpha,25-dihydroxyvitamin D3-membrane associated, rapid response steroid binding protein expression in mouse odontoblasts by 1alpha,25-(OH)2D3.

    PubMed

    Teillaud, Christophe; Nemere, Ilka; Boukhobza, Florine; Mathiot, Claire; Conan, Nicole; Oboeuf, Martine; Hotton, Dominique; Macdougall, Mary; Berdal, Ariane

    2005-01-01

    The rapid, nongenomic effects of 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3 have been related to a 1,25D3-membrane associated, rapid response steroid binding protein or 1,25D3-[MARRS]bp, with a molecular weight of 65 kDa, in several tissues and species. Currently, no information is available concerning the nongenomic responses to 1alpha,25-(OH)2D3 in dental tissues. In order to investigate the expression of 1,25D3-[MARRS]bp in dental cells, in the presence or absence of 1alpha,25-(OH)2D3, we have used rabbit polyclonal antibodies directed against the N-terminus of the 1,25D3-[MARRS]bp (Ab099) that recognizes the 1alpha,25-(OH)2D3 binding protein in chick intestinal basolateral membranes and a mouse odontoblast-like cell line (MO6-G3). Western blotting and flow cytometric analyses with Ab099 specifically detected 1,25D3-[MARRS]bp in MO6-G3 cells. Moreover, 1,25D3-[MARRS]bp was up-regulated, in vivo, in differentiated dental cells. Electron microscopic analysis confirmed the plasma membrane localization of this binding protein and also showed its intracellular presence. Incubation of MO6-G3 cells with different doses of 1alpha,25-(OH)2D3 for 36 h resulted in an inhibition of 1,25D3-[MARRS]bp expression with a maximal effect at 50 nM steroid. In addition, the culture media of MO6-G3 cells contains immunoreactive 1,25D3-[MARRS]bp. Immunogold positive membrane vesicle-like structures are present in the extracellular matrix of MO6-G3 cells. Altogether, these results indicate that the 1,25D3-[MARRS]bp expression in MO6-G3 cells is modulated by 1alpha,25-(OH)2D3. In conclusion, this 1alpha,25-(OH)2D3 binding protein could play an important role in the rapid, nongenomic responses to 1alpha,25-(OH)2D3 in dental cells.

  9. Effects of 1,25(OH)2 D3 and 25(OH)D3 on C2C12 Myoblast Proliferation, Differentiation, and Myotube Hypertrophy.

    PubMed

    van der Meijden, K; Bravenboer, N; Dirks, N F; Heijboer, A C; den Heijer, M; de Wit, G M J; Offringa, C; Lips, P; Jaspers, R T

    2016-11-01

    An adequate vitamin D status is essential to optimize muscle strength. However, whether vitamin D directly reduces muscle fiber atrophy or stimulates muscle fiber hypertrophy remains subject of debate. A mechanism that may affect the role of vitamin D in the regulation of muscle fiber size is the local conversion of 25(OH)D to 1,25(OH)2 D by 1α-hydroxylase. Therefore, we investigated in a murine C2C12 myoblast culture whether both 1,25(OH)2 D3 and 25(OH)D3 affect myoblast proliferation, differentiation, and myotube size and whether these cells are able to metabolize 25(OH)D3 and 1,25(OH)2 D3 . We show that myoblasts not only responded to 1,25(OH)2 D3 , but also to the precursor 25(OH)D3 by increasing their VDR mRNA expression and reducing their proliferation. In differentiating myoblasts and myotubes 1,25(OH)2 D3 as well as 25(OH)D3 stimulated VDR mRNA expression and in myotubes 1,25(OH)2 D3 also stimulated MHC mRNA expression. However, this occurred without notable effects on myotube size. Moreover, no effects on the Akt/mTOR signaling pathway as well as MyoD and myogenin mRNA levels were observed. Interestingly, both myoblasts and myotubes expressed CYP27B1 and CYP24 mRNA which are required for vitamin D3 metabolism. Although 1α-hydroxylase activity could not be shown in myotubes, after treatment with 1,25(OH)2 D3 or 25(OH)D3 myotubes showed strongly elevated CYP24 mRNA levels compared to untreated cells. Moreover, myotubes were able to convert 25(OH)D3 to 24R,25(OH)2 D3 which may play a role in myoblast proliferation and differentiation. These data suggest that skeletal muscle is not only a direct target for vitamin D3 metabolites, but is also able to metabolize 25(OH)D3 and 1,25(OH)2 D3 . J. Cell. Physiol. 231: 2517-2528, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  10. Highly Selective Dopamine D3 Receptor (D3R) Antagonists and Partial Agonists Based on Eticlopride and the D3R Crystal Structure: New Leads for Opioid Dependence Treatment.

    PubMed

    Kumar, Vivek; Bonifazi, Alessandro; Ellenberger, Michael P; Keck, Thomas M; Pommier, Elie; Rais, Rana; Slusher, Barbara S; Gardner, Eliot; You, Zhi-Bing; Xi, Zheng-Xiong; Newman, Amy Hauck

    2016-08-25

    The recent and precipitous increase in opioid analgesic abuse and overdose has inspired investigation of the dopamine D3 receptor (D3R) as a target for therapeutic intervention. Metabolic instability or predicted toxicity has precluded successful translation of previously reported D3R-selective antagonists to clinical use for cocaine abuse. Herein, we report a series of novel and D3R crystal structure-guided 4-phenylpiperazines with exceptionally high D3R affinities and/or selectivities with varying efficacies. Lead compound 19 was selected based on its in vitro profile: D3R Ki = 6.84 nM, 1700-fold D3R versus D2R binding selectivity, and its metabolic stability in mouse microsomes. Compound 19 inhibited oxycodone-induced hyperlocomotion in mice and reduced oxycodone-induced locomotor sensitization. In addition, pretreatment with 19 also dose-dependently inhibited the acquisition of oxycodone-induced conditioned place preference (CPP) in rats. These findings support the D3R as a target for opioid dependence treatment and compound 19 as a new lead molecule for development. PMID:27508895

  11. Association study of dopamine D3 receptor gene and schizophrenia

    SciTech Connect

    Kennedy, J.L.; Billett, E.A.; Macciardi, F.M.

    1995-12-18

    Several groups have reported an association between schizophrenia and the MscI polymorphism in the first exon of the dopamine D3 receptor gene (DRD3). We studied this polymorphism using a North American sample (117 patients plus 188 controls) and an Italian sample (97 patients plus 64 controls). In the first part of the study, we compared allele frequencies of schizophrenia patients and unmatched controls and observed a significant difference in the total sample (P = 0.01). The second part of the study involved a case control approach in which each schizophrenia patient was matched to a control of the same sex, and of similar age and ethnic background. The DRD3 allele frequencies of patients and controls revealed no significant difference between the two groups in the Italian (N = 53) or the North American (N = 54) matched populations; however, when these two matched samples were combined, a significant difference was observed (P = 0.026). Our results suggest that the MscI polymorphism may be associated with schizophrenia in the populations studied. 32 refs., 2 tabs.

  12. Ammonia Induces Autophagy through Dopamine Receptor D3 and MTOR.

    PubMed

    Li, Zhiyuan; Ji, Xinmiao; Wang, Wenchao; Liu, Juanjuan; Liang, Xiaofei; Wu, Hong; Liu, Jing; Eggert, Ulrike S; Liu, Qingsong; Zhang, Xin

    2016-01-01

    Hyperammonemia is frequently seen in tumor microenvironments as well as in liver diseases where it can lead to severe brain damage or death. Ammonia induces autophagy, a mechanism that tumor cells may use to protect themselves from external stresses. However, how cells sense ammonia has been unclear. Here we show that culture medium alone containing Glutamine can generate milimolar of ammonia at 37 degrees in the absence of cells. In addition, we reveal that ammonia acts through the G protein-coupled receptor DRD3 (Dopamine receptor D3) to induce autophagy. At the same time, ammonia induces DRD3 degradation, which involves PIK3C3/VPS34-dependent pathways. Ammonia inhibits MTOR (mechanistic target of Rapamycin) activity and localization in cells, which is mediated by DRD3. Therefore, ammonia has dual roles in autophagy: one to induce autophagy through DRD3 and MTOR, the other to increase autophagosomal pH to inhibit autophagic flux. Our study not only adds a new sensing and output pathway for DRD3 that bridges ammonia sensing and autophagy induction, but also provides potential mechanisms for the clinical consequences of hyperammonemia in brain damage, neurodegenerative diseases and tumors.

  13. 2D/3D registration algorithm for lung brachytherapy

    SciTech Connect

    Zvonarev, P. S.; Farrell, T. J.; Hunter, R.; Wierzbicki, M.; Hayward, J. E.; Sur, R. K.

    2013-02-15

    Purpose: A 2D/3D registration algorithm is proposed for registering orthogonal x-ray images with a diagnostic CT volume for high dose rate (HDR) lung brachytherapy. Methods: The algorithm utilizes a rigid registration model based on a pixel/voxel intensity matching approach. To achieve accurate registration, a robust similarity measure combining normalized mutual information, image gradient, and intensity difference was developed. The algorithm was validated using a simple body and anthropomorphic phantoms. Transfer catheters were placed inside the phantoms to simulate the unique image features observed during treatment. The algorithm sensitivity to various degrees of initial misregistration and to the presence of foreign objects, such as ECG leads, was evaluated. Results: The mean registration error was 2.2 and 1.9 mm for the simple body and anthropomorphic phantoms, respectively. The error was comparable to the interoperator catheter digitization error of 1.6 mm. Preliminary analysis of data acquired from four patients indicated a mean registration error of 4.2 mm. Conclusions: Results obtained using the proposed algorithm are clinically acceptable especially considering the complications normally encountered when imaging during lung HDR brachytherapy.

  14. D3-instantons, mock theta series and twistors

    NASA Astrophysics Data System (ADS)

    Alexandrov, Sergei; Manschot, Jan; Pioline, Boris

    2013-04-01

    The D-instanton corrected hypermultiplet moduli space of type II string theory compactified on a Calabi-Yau threefold is known in the type IIA picture to be determined in terms of the generalized Donaldson-Thomas invariants, through a twistorial construction. At the same time, in the mirror type IIB picture, and in the limit where only D3-D1-D(-1)-instanton corrections are retained, it should carry an isometric action of the S-duality group SL(2, {Z} ). We prove that this is the case in the one-instanton approximation, by constructing a holomorphic action of SL(2, {Z} ) on the linearized twistor space. Using the modular invariance of the D4-D2-D0 black hole partition function, we show that the standard Darboux coordinates in twistor space have modular anomalies controlled by period integrals of a Siegel-Narain theta series, which can be canceled by a contact transformation generated by a holomorphic mock theta series.

  15. Thesis Abstract Levels and forms of vitamin D in broilers diets.

    PubMed

    Mesquita, F R; Silva, M I A; Bertechini, A G

    2016-05-09

    This study aimed to evaluate the concentration effects of two vitamin D isoforms, cholecalciferol (D3) and 25-hydroxycholecalciferol (25-OHD3) in broilers diets on performance, bone and physiological features of these birds. Of a total of 1920 one-day-old male chicks Cobb-500 were used from commercial hatchery, reared under bed creation systems. The animals were distributed in six treatments and eight replicates with 40 birds per treatment in a completely randomized design. The following vitamin D supplementation levels were applied: 70 and 87.5 μg/kg feed in initial phase; 56 and 70 μg/kg feed during the growth phase, and 35 and 47.35 μg/kg of feed in final phase of creation, obtained from two forms (D3 and 25-OHD3). The treatments consisted of supplementation of two levels from each isolated source and their associations (60% D3 + 40% 25-OHD3) according to the study phases. In the metabolism assay, 480 birds (14 and 35 days of age) were separated to be used for evaluation of calcium (Ca) and phosphorus (P) retention and excretion during the periods of 19 to 21 days and 40 to 42 days of age. The diets were based on corn and soybean meal, with supplementation of phytase (500 FTU/kg). The performance, bone characteristics, plasma levels, bone radiographic density, carcass yield, and P and Ca retention were evaluated. In the initial creation phase, we observed an increased P excretion by broilers fed diets supplemented with vitamin D3 (P < 0.05). In addition, the association between the two vitamin D isoforms resulted in higher retention of Ca and P than the birds fed diets supplemented only with vitamin D3 (P < 0.05), and higher P retention when compared to birds fed diets supplemented with 25-OHD3 (P < 0.05). Dietary supplemental 25-OHD3 at 87.5 μg/kg resulted in higher plasma levels of Ca in relation to the same supplemented source with 70 μg/kg at 21 days of age (P < 0.05). In the final phase, the birds fed diets supplemented with vitamin D3 presented the

  16. Thesis Abstract Levels and forms of vitamin D in broilers diets.

    PubMed

    Mesquita, F R; Silva, M I A; Bertechini, A G

    2016-01-01

    This study aimed to evaluate the concentration effects of two vitamin D isoforms, cholecalciferol (D3) and 25-hydroxycholecalciferol (25-OHD3) in broilers diets on performance, bone and physiological features of these birds. Of a total of 1920 one-day-old male chicks Cobb-500 were used from commercial hatchery, reared under bed creation systems. The animals were distributed in six treatments and eight replicates with 40 birds per treatment in a completely randomized design. The following vitamin D supplementation levels were applied: 70 and 87.5 μg/kg feed in initial phase; 56 and 70 μg/kg feed during the growth phase, and 35 and 47.35 μg/kg of feed in final phase of creation, obtained from two forms (D3 and 25-OHD3). The treatments consisted of supplementation of two levels from each isolated source and their associations (60% D3 + 40% 25-OHD3) according to the study phases. In the metabolism assay, 480 birds (14 and 35 days of age) were separated to be used for evaluation of calcium (Ca) and phosphorus (P) retention and excretion during the periods of 19 to 21 days and 40 to 42 days of age. The diets were based on corn and soybean meal, with supplementation of phytase (500 FTU/kg). The performance, bone characteristics, plasma levels, bone radiographic density, carcass yield, and P and Ca retention were evaluated. In the initial creation phase, we observed an increased P excretion by broilers fed diets supplemented with vitamin D3 (P < 0.05). In addition, the association between the two vitamin D isoforms resulted in higher retention of Ca and P than the birds fed diets supplemented only with vitamin D3 (P < 0.05), and higher P retention when compared to birds fed diets supplemented with 25-OHD3 (P < 0.05). Dietary supplemental 25-OHD3 at 87.5 μg/kg resulted in higher plasma levels of Ca in relation to the same supplemented source with 70 μg/kg at 21 days of age (P < 0.05). In the final phase, the birds fed diets supplemented with vitamin D3 presented the

  17. Exposure to Cigarette Smoke Reduces Vitamin D3 in the Blood Stream and Respiratory Tract

    MedlinePlus

    ... respiratory tract Share | Exposure to cigarette smoke reduces vitamin D3 in the blood stream and respiratory tract ... be understood as to how smoke causes inflammation. Vitamin D3 has anti-inflammatory and anti-bacterial effects. ...

  18. Interactive client side data visualization with d3.js

    NASA Astrophysics Data System (ADS)

    Rodzianko, A.; Versteeg, R.; Johnson, D. V.; Soltanian, M. R.; Versteeg, O. J.; Girouard, M.

    2015-12-01

    Geoscience data associated with near surface research and operational sites is increasingly voluminous and heterogeneous (both in terms of providers and data types - e.g. geochemical, hydrological, geophysical, modeling data, of varying spatiotemporal characteristics). Such data allows scientists to investigate fundamental hydrological and geochemical processes relevant to agriculture, water resources and climate change. For scientists to easily share, model and interpret such data requires novel tools with capabilities for interactive data visualization. Under sponsorship of the US Department of Energy, Subsurface Insights is developing the Predictive Assimilative Framework (PAF): a cloud based subsurface monitoring platform which can manage, process and visualize large heterogeneous datasets. Over the last year we transitioned our visualization method from a server side approach (in which images and animations were generated using Jfreechart and Visit) to a client side one that utilizes the D3 Javascript library. Datasets are retrieved using web service calls to the server, returned as JSON objects and visualized within the browser. Users can interactively explore primary and secondary datasets from various field locations. Our current capabilities include interactive data contouring and heterogeneous time series data visualization. While this approach is very powerful and not necessarily unique, special attention needs to be paid to latency and responsiveness issues as well as to issues as cross browser code compatibility so that users have an identical, fluid and frustration-free experience across different computational platforms. We gratefully acknowledge support from the US Department of Energy under SBIR Award DOE DE-SC0009732, the use of data from the Lawrence Berkeley National Laboratory (LBNL) Sustainable Systems SFA Rifle field site and collaboration with LBNL SFA scientists.

  19. Dopamine D3 Receptor Inactivation Attenuates Cocaine-Induced Conditioned Place Preference in Mice

    PubMed Central

    Song, Rui; Zhang, Hai-Ying; Peng, Xiao-Qing; Su, Rui-Bin; Yang, Ri-Fang; Li, Jin; Xi, Zheng-Xiong; Gardner, Eliot L.

    2013-01-01

    The dopamine (DA) D3 receptor (D3R) has received much attention in medication development for treatment of addiction. However, the functional role of the D3R in drug reward and addiction has been a matter of debate. We recently reported that D3 receptor-knockout (D3−/−) mice display increased vulnerability to cocaine self-administration, which we interpret as a compensatory response to attenuated cocaine reward after D3R deletion. Here we report that D3−/− mice displayed attenuated cocaine-induced conditioned place response (CPP) compared to wild-type mice. Similarly, blockade of brain D3Rs by YQA-14, a novel DA D3 receptor antagonist, significantly and dose-dependently inhibits acquisition and expression of cocaine-induced CPP in WT mice, but not in D3−/− mice. These findings suggest that: 1) D3Rs play an important role in mediating cocaine’s rewarding effects; and 2) YQA-14 is a highly potent and selective D3R antagonist in vivo, which deserves further study as a candidate for treatment of cocaine addiction. PMID:23643749

  20. 42 CFR 51d.3 - Who is eligible for an award under this subpart?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Who is eligible for an award under this subpart? 51d.3 Section 51d.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MENTAL HEALTH AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.3 Who is eligible for...

  1. 42 CFR 51d.3 - Who is eligible for an award under this subpart?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Who is eligible for an award under this subpart? 51d.3 Section 51d.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MENTAL HEALTH AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.3 Who is eligible for...

  2. 42 CFR 51d.3 - Who is eligible for an award under this subpart?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Who is eligible for an award under this subpart? 51d.3 Section 51d.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MENTAL HEALTH AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.3 Who is eligible for...

  3. 42 CFR 51d.3 - Who is eligible for an award under this subpart?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Who is eligible for an award under this subpart? 51d.3 Section 51d.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MENTAL HEALTH AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.3 Who is eligible for...

  4. 42 CFR 51d.3 - Who is eligible for an award under this subpart?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Who is eligible for an award under this subpart? 51d.3 Section 51d.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MENTAL HEALTH AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.3 Who is eligible for...

  5. Sunlight regulates the cutaneous production of vitamin D3 by causing its photodegradation

    SciTech Connect

    Webb, A.R.; DeCosta, B.R.; Holick, M.F.

    1989-05-01

    Exposure to sunlight initiates the formation of vitamin D3 in skin as the UV B radiation in the solar spectrum causes the photoconversion of 7-dehydrocholesterol to previtamin D3. A heat-induced isomerization then converts previtamin D3 to vitamin D3 over a period of days. A number of irradiation products of vitamin D3 are known to form upon irradiation with high intensity UV radiation, but the effect of subsequent exposures to sunlight on the vitamin D3 formed in skin is not known. To investigate this phenomenon, human skin containing vitamin D3 was exposed to sunlight in Boston. A model system of (/sup 3/H)vitamin D3 in methanol was also used to study the effects of sunlight on vitamin D3 throughout the year. Vitamin D3 proved to be exquisitely sensitive to sunlight, and once formed in the skin, exposure to sunlight resulted in its rapid photodegradation to a variety of photoproducts, including 5,6-transvitamin D3, suprasterol I, and suprasterol II.

  6. UV-Stressed Daphnia pulex Increase Fitness through Uptake of Vitamin D3.

    PubMed

    Connelly, Sandra J; Walling, Kelly; Wilbert, Steven A; Catlin, Diane M; Monaghan, Cailin E; Hlynchuk, Sofiya; Meehl, Pamela G; Resch, Lauren N; Carrera, J Valerie; Bowles, Stephanie M; Clark, Michael D; Tan, Loraine T; Cody, Jeremy A

    2015-01-01

    Ultraviolet radiation is known to be highly variable in aquatic ecosystems. It has been suggested that UV-exposed organisms may demonstrate enough phenotypic plasticity to maintain the relative fitness of natural populations. Our long-term objective is to determine the potential photoprotective effect of vitamin D3 on Daphnia pulex exposed to acute or chronic UV radiation. Herein we report our initial findings in this endeavor. D. pulex survival and reproduction (fitness) was monitored for 5 d as a proof of concept study. Significantly higher fitness was observed in the D. pulex with D3 than those without (most extreme effects observed were 0% survival in the absence of D3 and 100% with 10 ppm D3). Vitamin D3 was isolated from the culture media, the algal food (Pseudokirchneriella), and the D. pulex and quantified using high performance liquid chromatography (HPLC). Vitamin D3 was fluorescently labeled using a phenothiazinium dye and added to cultures of D. pulex. Images demonstrating the uptake of D3 into the tissues and carapace of the D. pulex were acquired. Our initial findings suggest a positive role for D3 in ecosystems as both UV-stressed algae and Daphnia sequester D3, and D. pulex demonstrate increased fitness in the presence of D3.

  7. UV-Stressed Daphnia pulex Increase Fitness through Uptake of Vitamin D3

    PubMed Central

    Walling, Kelly; Wilbert, Steven A.; Catlin, Diane M.; Monaghan, Cailin E.; Hlynchuk, Sofiya; Meehl, Pamela G.; Resch, Lauren N.; Carrera, J. Valerie; Bowles, Stephanie M.; Clark, Michael D.

    2015-01-01

    Ultraviolet radiation is known to be highly variable in aquatic ecosystems. It has been suggested that UV-exposed organisms may demonstrate enough phenotypic plasticity to maintain the relative fitness of natural populations. Our long-term objective is to determine the potential photoprotective effect of vitamin D3 on Daphnia pulex exposed to acute or chronic UV radiation. Herein we report our initial findings in this endeavor. D. pulex survival and reproduction (fitness) was monitored for 5 d as a proof of concept study. Significantly higher fitness was observed in the D. pulex with D3 than those without (most extreme effects observed were 0% survival in the absence of D3 and 100% with 10 ppm D3). Vitamin D3 was isolated from the culture media, the algal food (Pseudokirchneriella), and the D. pulex and quantified using high performance liquid chromatography (HPLC). Vitamin D3 was fluorescently labeled using a phenothiazinium dye and added to cultures of D. pulex. Images demonstrating the uptake of D3 into the tissues and carapace of the D. pulex were acquired. Our initial findings suggest a positive role for D3 in ecosystems as both UV-stressed algae and Daphnia sequester D3, and D. pulex demonstrate increased fitness in the presence of D3. PMID:26147286

  8. 1,25(OH)2D3 increases membrane associated protein kinase C in MDBK cells.

    PubMed

    Simboli-Campbell, M; Franks, D J; Welsh, J

    1992-01-01

    To determine whether 1,25-dihydroxycholecalciferol [1,25(OH)2D3] affects protein kinase C (PKC) activity in kidney, as has been demonstrated in HL-60 cells we measured 1,25(OH)2D3 binding, PKC activity and PKC immunoreactivity in Madin Darby bovine kidney (MDBK) cells, a normal renal epithelial cell line derived from bovine kidney. Our data demonstrate that MDBK cells exhibit specific high affinity binding for 1,25(OH)2D3, indicating the presence of the vitamin D receptor (VDR). Treatment of MDBK cells with 1,25(OH)2D3 for 24 h increased membrane PKC activity and immunoreactivity. The effect of 1,25(OH)2D3 was dose-dependent, with a peak effect observed at 10(-7)M 1,25(OH)2D3. The 1,25(OH)2D3 induced increase in membrane PKC was paralleled by a comparable decrease in cytosolic PKC activity and amount. Although time course studies were consistent with a VDR mediated effect of 1,25(OH)2D3 on PKC protein synthesis, total PKC activity was not increased by 1,25(OH)2D3, suggesting an effect on PKC translocation or localization. These results suggest that 1,25(OH)2D3 modulates PKC mediated events in kidney, a classic target for this steroid hormone.

  9. Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis.

    PubMed

    Wang, Tiantian; Shan, Ling; Du, Lin; Feng, Junyan; Xu, Zhida; Staal, Wouter G; Jia, Feiyong

    2016-04-01

    Vitamin D may play an important role in the etiology of Autism Spectrum Disorders (ASD). Vitamin D is regarded as a neuroactive steroid affecting brain development and function. It plays an essential role in myelination, which is important for connectivity in the brain. Studies have shown that decreased vitamin D levels in patients, decreased maternal vitamin D levels during pregnancy, and decreased exposure to solar UVB might increase the risk for ASD. In addition, autism symptoms and global functioning may improve after vitamin D supplementation. Here, we sought to aggregate information from previous publications on vitamin D levels and ASD, in order to achieve a higher statistical power and thereby to determine the validity of vitamin D deficiency as a risk factor for ASD. For this meta-analysis, 11 studies met the inclusion and exclusion criteria, accounting for a total of 870 ASD patients and 782 healthy controls. Levels of serum 25(OH) D in participants with ASD were significantly lower than controls, suggesting that lower vitamin D level might be a risk factor for ASD. PMID:26514973

  10. Seasonal variations of 25 hydroxyvitamin D and parathyroid hormone in Ushuaia (Argentina), the southernmost city of the world.

    PubMed

    Oliveri, M B; Ladizesky, M; Mautalen, C A; Alonso, A; Martinez, L

    1993-01-01

    Serum levels of calcium, phosphorus, alkaline phosphatase, 250HD, 1.25(OH)2D and PTH were studied in a group of 42 children aged 8.5 +/- 1.8 years (X +/- SD) from the city of Ushuaia (latitude 55 degrees S), at both the end of the winter and the end of summer. Calcium, phosphorus, alkaline phosphatase and 1.25(OH)2D serum levels were not different in summer and winter. The levels of serum 25OHD were significantly higher in summer (18.4 +/- 7.3 ng/ml) than in winter (9.8 +/- 3.8 ng/ml P < 0.001). The levels of 25OHD in children with fair or dark skin were similar in winter but were significantly higher in children with fair skin in summer (20.0 +/- 7.2 ng/l vs 15.3 +/- 5.1 ng/ml (P < 0.05). Serum levels of PTH were higher in winter (58.2 +/- 30.5 pg/ml) than in summer (47.9 +/- 28.3 pg/ml) (P < 0.03). The results demonstrate the existence of a population with low serum levels of 25OHD in winter. The higher levels of PTH in winter when serum 25OHD levels are lower could be the cause of the lack of seasonal variation in serum calcium and 1.25(OH)2D levels. Further studies are needed to establish whether these changes besides increasing the incidence of rickets, could also affect the mineral density of the skeleton in the population of this vitamin-D-deficient area.

  11. Associations between serum 25-hydroxyvitamin D and bone turnover markers in a population based sample of German children.

    PubMed

    Thiering, E; Brüske, I; Kratzsch, J; Hofbauer, L C; Berdel, D; von Berg, A; Lehmann, I; Hoffmann, B; Bauer, C P; Koletzko, S; Heinrich, J

    2015-01-01

    Severe vitamin D deficiency is known to cause rickets, however epidemiological studies and RCTs did not reveal conclusive associations for other parameters of bone health. In our study, we aimed to investigate the association between serum levels of 25(OH) vitamin D and bone turnover markers in a population-based sample of children. 25(OH)D, calcium (Ca), osteocalcin (OC), and β-Crosslaps (β-CTx) were measured in 2798 ten-year-old children from the German birth cohorts GINIplus and LISAplus. Linear regression was used to determine the association between bone turnover markers and 25(OH)D levels. 25(OH)D, OC, and β-CTx showed a clear seasonal variation. A 10 nmol/l increase in 25(OH)D was significantly associated with a 10.5 ng/l decrease (p < 0.001) in β-CTx after adjustment for design, sex, fasting status, time of blood drawn, BMI, growth rate, and detectable testosterone/estradiol. For OC alone no significant association with 25(OH)D was observed, whereas the β-CTx-to-OC ratio was inversely associated with 25(OH)D (-1.7% change, p < 0.001). When stratifying the analyses by serum calcium levels, associations were stronger in children with Ca levels below the median. This study in school-aged children showed a seasonal variation of 25(OH)D and the bone turnover markers OC and β-CTx. Furthermore a negative association between 25(OH)D and the bone resorption marker β-CTx was observed. PMID:26667774

  12. Seasonal Epidemiology of Serum 25-Hydroxyvitamin D Concentrations among Healthy Adults Living in Rural and Urban Areas in Mongolia

    PubMed Central

    Bromage, Sabri; Rich-Edwards, Janet W.; Tselmen, Daria; Baylin, Ana; Houghton, Lisa A.; Baasanjav, Nachin; Ganmaa, Davaasambuu

    2016-01-01

    Many factors put Mongolians at risk of vitamin D deficiency. Despite low levels observed in Mongolian children and pregnant women, there are few data published on the vitamin D status of non-pregnant adults. Between summer 2011 and winter 2013, paired summer and winter blood samples were collected from 320 healthy men and women (20–58 years) living in eight Mongolian provinces. Mean serum 25(OH)D concentrations were 22.5 ng/mL (95% CI: 14.5, 32.5) in summer and 7.7 ng/mL (95% CI: 4.6, 10.8) in winter, with a distribution (<10/10–20/20–30/≥30 ng/mL) of 3.1%/39.3%/39.6%/17.9% in summer and 80.1%/19.5%/0.3%/0.0% in winter. Residents of the capital, Ulaanbaatar, had lower levels in both seasons than any other region, whereas residents of the Gobi desert had the highest. In summer, indoor workers had significantly lower levels than outdoor workers (−2.3 ng/mL; 95% CI: −4.1, −5.7) while levels in males exceeded those in females (4.0 ng/mL; 95% CI: 2.3, 5.7). Effects of region, occupation, and sex were also significant in multivariable regression. In conclusion, Mongolian adults had extremely low serum 25(OH)D, particularly in winter, when 80.1% had concentrations below 10 ng/mL. These results indicate a need for effective vitamin D interventions for the Mongolian adult population, particularly among women and residents of Ulaanbaatar. PMID:27669291

  13. Chemoprevention activity of 25-hydroxyvitamin D in the MMTV-PyMT mouse model of breast cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Development of oncologic conditions is often linked to inadequate vitamin D status. The chemoprevention ability of this molecule is of high interest for breast cancer, the most common malignancy in women worldwide. Current effective vitamin D analogs including the naturally occurring active metabol...

  14. Seasonal Epidemiology of Serum 25-Hydroxyvitamin D Concentrations among Healthy Adults Living in Rural and Urban Areas in Mongolia.

    PubMed

    Bromage, Sabri; Rich-Edwards, Janet W; Tselmen, Daria; Baylin, Ana; Houghton, Lisa A; Baasanjav, Nachin; Ganmaa, Davaasambuu

    2016-01-01

    Many factors put Mongolians at risk of vitamin D deficiency. Despite low levels observed in Mongolian children and pregnant women, there are few data published on the vitamin D status of non-pregnant adults. Between summer 2011 and winter 2013, paired summer and winter blood samples were collected from 320 healthy men and women (20-58 years) living in eight Mongolian provinces. Mean serum 25(OH)D concentrations were 22.5 ng/mL (95% CI: 14.5, 32.5) in summer and 7.7 ng/mL (95% CI: 4.6, 10.8) in winter, with a distribution (<10/10-20/20-30/≥30 ng/mL) of 3.1%/39.3%/39.6%/17.9% in summer and 80.1%/19.5%/0.3%/0.0% in winter. Residents of the capital, Ulaanbaatar, had lower levels in both seasons than any other region, whereas residents of the Gobi desert had the highest. In summer, indoor workers had significantly lower levels than outdoor workers (-2.3 ng/mL; 95% CI: -4.1, -5.7) while levels in males exceeded those in females (4.0 ng/mL; 95% CI: 2.3, 5.7). Effects of region, occupation, and sex were also significant in multivariable regression. In conclusion, Mongolian adults had extremely low serum 25(OH)D, particularly in winter, when 80.1% had concentrations below 10 ng/mL. These results indicate a need for effective vitamin D interventions for the Mongolian adult population, particularly among women and residents of Ulaanbaatar. PMID:27669291

  15. Pharmacological targeting of dopamine D3 receptors: Possible clinical applications of selective drugs.

    PubMed

    Pich, Emilio Merlo; Collo, Ginetta

    2015-09-01

    Dopamine D3 receptors have been pharmacologically engaged in humans since the development of the first antipsychotics and ergot-derivative dopamine (DA) agonists, even without knowing it. These agents were generally non-selective, developed primarily to target D2 receptors. In the last 10 years the understanding of the clinical implication of D3 receptors has been progressing also due to the identification of D3 gene polymorphisms, the use of more selective PET ligands such as [(11)C]-(+)-PHNO and the learning regarding the clinical use of the D3-preferential D2/D3 agonists ropinirole and pramipexole. A new specific neuroplasticity role of D3 receptor regarding dendrite arborisation outgrowth in dopaminergic neurons was also proposed to support, at least in part, the slowing of disease observed in subjects with Parkinson׳s Disease treated with DA agonists. Similar mechanisms could be at the basis of the antidepressant-like effects observed with DA agonists when co-administered with standard of care. Severe adverse event occurring with the use of anti-parkinsonian DA agonists in predisposed subjects, i.e., impulse control disorders, are now suggested to be putatively related to overactive D3 receptors. Not surprisingly, blockade of D3 receptors was proposed as treatment for addictive disorders, a goal that could be potentially achieved by repositioning buspirone, an anxiolytic drug with D3-preferential antagonistic features, or with novel selective D3 antagonists or partial agonists currently in development for schizophrenia. At the moment ABT-925 is the only selective D3 antagonist tested in schizophrenic patients in Phase II, showing an intriguing cognitive enhancing effects supported by preclinical data. Finally, exploratory pharmacogenetic analysis suggested that ABT-925 could be effective in a subpopulation of patients with a polymorphism on the D3 receptor, opening to a possible personalised medicine approach. PMID:26298833

  16. Noncalcemic actions of 1,25-dihydroxyvitamin D3 and clinical applications.

    PubMed

    Holick, M F

    1995-08-01

    Vitamin D is absolutely essential for the maintenance of a healthy skeleton. Without vitamin D, children develop rickets and adults exacerbate their osteoporosis and develop osteomalacia. Casual exposure to sunlight is the major source of vitamin D for most people. During exposure to sunlight, ultraviolet B photons photolyze cutaneous stores of 7-dehydrocholesterol to previtamin D3. Previtamin D3 undergoes a thermal isomerization to form vitamin D3. Increased skin pigmentation, changes in latitude, time of day, sunscreen use, and aging can have a marked influence on the cutaneous production of vitamin D3. Once vitamin D3 is formed in the skin or ingested in the diet, it must be hydroxylated in the liver and kidney to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. It is now recognized that a wide variety of tissues and cells, both related to calcium metabolism and unrelated to calcium metabolism, are target sites for 1,25(OH)2D3. 1,25(OH)2D3 stimulates intestinal calcium absorption and mobilizes stem cells to mobilize calcium stores from bone. Noncalcemic tissues that possess receptors for 1,25(OH)2D3 respond to the hormone in a variety of ways. Of great interest is that 1,25(OH)2D3 is a potent antiproliferative and prodifferentiation mediator. As a result, 1,25(OH)2D3 and its analogs have wide clinical application in such diverse clinical disorders as rheumatoid and psoriatic arthritis; diabetes mellitus type I; hypertension; cardiac arrhythmias; seizure disorders; cancers of the breast, prostate, and colon; some leukemias and myeloproliferative disorders; chemotherapy-induced hair loss; and skin rejuvenation as well as skin diseases like psoriasis and ichthyosis.

  17. Noncalcemic actions of 1,25-dihydroxyvitamin D3 and clinical applications.

    PubMed

    Holick, M F

    1995-08-01

    Vitamin D is absolutely essential for the maintenance of a healthy skeleton. Without vitamin D, children develop rickets and adults exacerbate their osteoporosis and develop osteomalacia. Casual exposure to sunlight is the major source of vitamin D for most people. During exposure to sunlight, ultraviolet B photons photolyze cutaneous stores of 7-dehydrocholesterol to previtamin D3. Previtamin D3 undergoes a thermal isomerization to form vitamin D3. Increased skin pigmentation, changes in latitude, time of day, sunscreen use, and aging can have a marked influence on the cutaneous production of vitamin D3. Once vitamin D3 is formed in the skin or ingested in the diet, it must be hydroxylated in the liver and kidney to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. It is now recognized that a wide variety of tissues and cells, both related to calcium metabolism and unrelated to calcium metabolism, are target sites for 1,25(OH)2D3. 1,25(OH)2D3 stimulates intestinal calcium absorption and mobilizes stem cells to mobilize calcium stores from bone. Noncalcemic tissues that possess receptors for 1,25(OH)2D3 respond to the hormone in a variety of ways. Of great interest is that 1,25(OH)2D3 is a potent antiproliferative and prodifferentiation mediator. As a result, 1,25(OH)2D3 and its analogs have wide clinical application in such diverse clinical disorders as rheumatoid and psoriatic arthritis; diabetes mellitus type I; hypertension; cardiac arrhythmias; seizure disorders; cancers of the breast, prostate, and colon; some leukemias and myeloproliferative disorders; chemotherapy-induced hair loss; and skin rejuvenation as well as skin diseases like psoriasis and ichthyosis. PMID:8579891

  18. Characterization of D-3-hydroxybutyrylcarnitine (ketocarnitine): an identified ketosis-induced metabolite.

    PubMed

    Soeters, Maarten R; Serlie, Mireille J; Sauerwein, Hans P; Duran, Marinus; Ruiter, Jos P; Kulik, Willem; Ackermans, Mariëtte T; Minkler, Paul E; Hoppel, Charles L; Wanders, Ronald J A; Houten, Sander M

    2012-07-01

    Hydroxybutyrylcarnitine (HB-carnitine) is a metabolite that has been associated with insulin resistance and type 2 diabetes mellitus. It is currently unknown whether HB-carnitine can be produced from D-3-hydroxybutyrate (D-3HB), a ketone body; but its formation from L-3-HB-CoA, a fatty acid β-oxidation intermediate, is well established. We aimed to assess which stereoisomers of 3-HB-carnitine are present in vivo. Ketosis and increased fatty acid oxidation were induced in 12 lean healthy men by a 38-hour fasting period. The D-3HB kinetics (stable isotope technique) and stereoisomers of muscle 3-HB-carnitine (high-performance liquid chromatography/ultra-performance liquid chromatography-tandem mass spectrometry) were measured. Muscle D-3HB-carnitine content was much higher compared with L-3HB-carnitine. In addition, muscle D-3HB-carnitine correlated significantly with D-3-HB production. Following the finding that a ketone body can be converted into a carnitine ester in vivo, we show in vitro that D-3-HB can be converted into HB-carnitine (ketocarnitine) via an acyl-CoA synthetase reaction in several tissues including human muscle. During fasting, HB-carnitine in muscle is derived mainly from the ketone body D-3HB. The role of D-3HB-carnitine synthesis in metabolism remains to be elucidated.

  19. Methamphetamine-induced locomotor activity and behavioral sensitization: are dopamine d3 receptors involved?

    PubMed

    Jones, C D; Bartee, J A; Leite-Browning, M L; Blackshear, M A

    2007-05-15

    Drug sensitization is a behavioral phenomenon that occurs following repeated administration of methamphetamine (METH) and similar CNS stimulants. The mechanism of drug sensitization is unknown, but is believed to be due to downregulation of dopamine D3 receptors. It is hypothesized that repeated administration of dopamine D3 agonists results in downregulation of D3 receptors in methamphetamine-induced (METH-IND) sensitization. Furthermore, repeated administration of dopamine D3 antagonists and METH cause upregulation of D3 receptors and block METH-IND sensitization. The objective of this study was to determine the role of D3 receptors in METH-IND sensitization. To test these hypotheses, male mice received chronic injections (i.p.) of 2 mg/kg of the dopamine D3 agonist, PD128907 plus 0.5 mg/kg of METH or 8 mg/kg of D3 antagonist, U99194A and 0.5 mg\\kg of METH daily for 7-days. Drugs were withdrawn on day 8, and METH-IND sensitization was determined on day 18. Locomotor activity was measured for 75 minutes immediately after METH administration in an activity monitor. Acute administration of PD128907 decreased METH-IND locomotion, p < 0. 01, and acute U99194A increased it. However, chronic administration of these drugs did not alter the locomotor effects of METH (p > 0.05). These findings support in-part the hypothesis that dopamine D3 receptors are downregulated in METH-IND sensitization.

  20. Formation of fatty acid esterified vitamin D3 in rat skin by exposure to ultraviolet radiation

    SciTech Connect

    Takada, K.

    1983-04-01

    The formation of fatty acid esters of vitamin D3 was demonstrated in rat skin exposed to artificial ultraviolet rays by using multi-dimensional high-performance liquid chromatography, ultraviolet spectrophotometry, and gas-liquid chromatography-mass spectrometry. This result indicated that the fatty acid esters of 7-dehydrocholesterol in rat skin (at least 80% of 7-dehydrocholesterol in rat skin is esterified) is also isomerized into vitamin D3 ester in vivo. The initial percentage of the esterified form was 84.3% and this did not significantly change up to the time when about half of the skin total vitamin D3 disappeared (2 days). Consequently, it was speculated that the vitamin D3 ester was delivered into the blood circulation from skin without having been hydrolyzed. This was supported by the presence of vitamin D3 ester in rat plasma exposed to ultraviolet radiation. In addition, in connection with the study of the restriction of vitamin D3 synthesis, distribution of total vitamin D3 in rat skin exposed to ultraviolet irradiation in vivo was compared with that in isolated skin exposed to ultraviolet radiation. The dermal layer of the isolated skin contained about 4 times more total vitamin D3 than that of in vivo skin. This finding suggests not only that ultraviolet rays could not penetrate deeply into the in vivo skin, but that the restriction of cutaneous synthesis of vitamin D3 observed in vivo may arise from this reduced penetration of ultraviolet rays.

  1. Characterization of the translocation process of vitamin D3 from the skin into the circulation.

    PubMed

    Tian, X Q; Chen, T C; Lu, Z; Shao, Q; Holick, M F

    1994-08-01

    The cutaneous synthesis of vitamin D3 and the subsequent translocation of vitamin D3 into the circulation are two key steps in the vitamin D endocrine system. To study the kinetic aspects of cutaneous synthesis and translocation of vitamin D3, both in vitro and in vivo chicken models have been developed. To assess the capacity of chicken skin to generate vitamin D3, the concentrations of 7-dehydrocholesterol (7-DHC) in different skin areas were determined. It was found that the highest concentration of 7-DHC was in the leg skin (3524 +/- 937 ng cm-2), which was about 30 times greater than that in the back (120 +/- 62 ng cm-2). Whole body exposure of chickens to UV-B radiation (0.5 J cm-2) resulted in the production of previtamin D3 (preD3) in the skin of the legs and feet (43 +/- 7 and 54 +/- 17 ng cm-2, respectively), whereas no preD3 was detected in the back skin. In vitro, at 40 C, the forward (k1) and reverse (k2) rate constants of the preD3<-->vitamin D3 reaction in the leg skin were greatly increased compared to those in n-hexane (k1, 0.367 vs. 0.0369 h-1; k2, 0.042 vs. 0.0059 h-1). In vivo, the determined rate constants k1, k2, and k3 for the consecutive reactions preD3<-->vitamin D3-->vitamin D3 were 0.257, 0.034, and 0.114 h-1, respectively. To evaluate the circulating concentration of vitamin D3 in response to UV-B radiation, chicken legs were irradiated. The time course revealed a 4-fold increase in the circulating concentration of vitamin D3, with a peak about 30 h postradiation. No appreciable amount of preD3 could be detected in the circulation in the early hours after UV-B radiation, suggesting the existence of a process responsible for the specific translocation of vitamin D3 from the skin into the circulation. PMID:8033813

  2. Reduced sleep duration mediates decreases in striatal D2/D3 receptor availability in cocaine abusers.

    PubMed

    Wiers, C E; Shumay, E; Cabrera, E; Shokri-Kojori, E; Gladwin, T E; Skarda, E; Cunningham, S I; Kim, S W; Wong, T C; Tomasi, D; Wang, G-J; Volkow, N D

    2016-01-01

    Neuroimaging studies have documented reduced striatal dopamine D2/D3 receptor (D2/D3R) availability in cocaine abusers, which has been associated with impaired prefrontal activity and vulnerability for relapse. However, the mechanism(s) underlying the decreases in D2/D3R remain poorly understood. Recent studies have shown that sleep deprivation is associated with a downregulation of striatal D2/D3R in healthy volunteers. As cocaine abusers have disrupted sleep patterns, here we investigated whether reduced sleep duration mediates the relationship between cocaine abuse and low striatal D2/D3R availability. We used positron emission tomography with [(11)C]raclopride to measure striatal D2/D3R availability in 24 active cocaine abusers and 21 matched healthy controls, and interviewed them about their daily sleep patterns. Compared with controls, cocaine abusers had shorter sleep duration, went to bed later and reported longer periods of sleep disturbances. In addition, cocaine abusers had reduced striatal D2/D3R availability. Sleep duration predicted striatal D2/D3R availability and statistically mediated the relationship between cocaine abuse and striatal D2/D3R availability. These findings suggest that impaired sleep patterns contribute to the low striatal D2/D3R availability in cocaine abusers. As sleep impairments are similarly observed in other types of substance abusers (for example, alcohol and methamphetamine), this mechanism may also underlie reductions in D2/D3R availability in these groups. The current findings have clinical implications suggesting that interventions to improve sleep patterns in cocaine abusers undergoing detoxification might be beneficial in improving their clinical outcomes. PMID:26954979

  3. Reduced sleep duration mediates decreases in striatal D2/D3 receptor availability in cocaine abusers

    PubMed Central

    Wiers, C E; Shumay, E; Cabrera, E; Shokri-Kojori, E; Gladwin, T E; Skarda, E; Cunningham, S I; Kim, S W; Wong, T C; Tomasi, D; Wang, G-J; Volkow, N D

    2016-01-01

    Neuroimaging studies have documented reduced striatal dopamine D2/D3 receptor (D2/D3R) availability in cocaine abusers, which has been associated with impaired prefrontal activity and vulnerability for relapse. However, the mechanism(s) underlying the decreases in D2/D3R remain poorly understood. Recent studies have shown that sleep deprivation is associated with a downregulation of striatal D2/D3R in healthy volunteers. As cocaine abusers have disrupted sleep patterns, here we investigated whether reduced sleep duration mediates the relationship between cocaine abuse and low striatal D2/D3R availability. We used positron emission tomography with [11C]raclopride to measure striatal D2/D3R availability in 24 active cocaine abusers and 21 matched healthy controls, and interviewed them about their daily sleep patterns. Compared with controls, cocaine abusers had shorter sleep duration, went to bed later and reported longer periods of sleep disturbances. In addition, cocaine abusers had reduced striatal D2/D3R availability. Sleep duration predicted striatal D2/D3R availability and statistically mediated the relationship between cocaine abuse and striatal D2/D3R availability. These findings suggest that impaired sleep patterns contribute to the low striatal D2/D3R availability in cocaine abusers. As sleep impairments are similarly observed in other types of substance abusers (for example, alcohol and methamphetamine), this mechanism may also underlie reductions in D2/D3R availability in these groups. The current findings have clinical implications suggesting that interventions to improve sleep patterns in cocaine abusers undergoing detoxification might be beneficial in improving their clinical outcomes. PMID:26954979

  4. Condensin II Subunit dCAP-D3 Restricts Retrotransposon Mobilization in Drosophila Somatic Cells

    PubMed Central

    Schuster, Andrew T.; Sarvepalli, Kavitha; Murphy, Eain A.; Longworth, Michelle S.

    2013-01-01

    Retrotransposon sequences are positioned throughout the genome of almost every eukaryote that has been sequenced. As mobilization of these elements can have detrimental effects on the transcriptional regulation and stability of an organism's genome, most organisms have evolved mechanisms to repress their movement. Here, we identify a novel role for the Drosophila melanogaster Condensin II subunit, dCAP-D3 in preventing the mobilization of retrotransposons located in somatic cell euchromatin. dCAP-D3 regulates transcription of euchromatic gene clusters which contain or are proximal to retrotransposon sequence. ChIP experiments demonstrate that dCAP-D3 binds to these loci and is important for maintaining a repressed chromatin structure within the boundaries of the retrotransposon and for repressing retrotransposon transcription. We show that dCAP-D3 prevents accumulation of double stranded DNA breaks within retrotransposon sequence, and decreased dCAP-D3 levels leads to a precise loss of retrotransposon sequence at some dCAP-D3 regulated gene clusters and a gain of sequence elsewhere in the genome. Homologous chromosomes exhibit high levels of pairing in Drosophila somatic cells, and our FISH analyses demonstrate that retrotransposon-containing euchromatic loci are regions which are actually less paired than euchromatic regions devoid of retrotransposon sequences. Decreased dCAP-D3 expression increases pairing of homologous retrotransposon-containing loci in tissue culture cells. We propose that the combined effects of dCAP-D3 deficiency on double strand break levels, chromatin structure, transcription and pairing at retrotransposon-containing loci may lead to 1) higher levels of homologous recombination between repeats flanking retrotransposons in dCAP-D3 deficient cells and 2) increased retrotransposition. These findings identify a novel role for the anti-pairing activities of dCAP-D3/Condensin II and uncover a new way in which dCAP-D3/Condensin II influences local

  5. Condensin II subunit dCAP-D3 restricts retrotransposon mobilization in Drosophila somatic cells.

    PubMed

    Schuster, Andrew T; Sarvepalli, Kavitha; Murphy, Eain A; Longworth, Michelle S

    2013-10-01

    Retrotransposon sequences are positioned throughout the genome of almost every eukaryote that has been sequenced. As mobilization of these elements can have detrimental effects on the transcriptional regulation and stability of an organism's genome, most organisms have evolved mechanisms to repress their movement. Here, we identify a novel role for the Drosophila melanogaster Condensin II subunit, dCAP-D3 in preventing the mobilization of retrotransposons located in somatic cell euchromatin. dCAP-D3 regulates transcription of euchromatic gene clusters which contain or are proximal to retrotransposon sequence. ChIP experiments demonstrate that dCAP-D3 binds to these loci and is important for maintaining a repressed chromatin structure within the boundaries of the retrotransposon and for repressing retrotransposon transcription. We show that dCAP-D3 prevents accumulation of double stranded DNA breaks within retrotransposon sequence, and decreased dCAP-D3 levels leads to a precise loss of retrotransposon sequence at some dCAP-D3 regulated gene clusters and a gain of sequence elsewhere in the genome. Homologous chromosomes exhibit high levels of pairing in Drosophila somatic cells, and our FISH analyses demonstrate that retrotransposon-containing euchromatic loci are regions which are actually less paired than euchromatic regions devoid of retrotransposon sequences. Decreased dCAP-D3 expression increases pairing of homologous retrotransposon-containing loci in tissue culture cells. We propose that the combined effects of dCAP-D3 deficiency on double strand break levels, chromatin structure, transcription and pairing at retrotransposon-containing loci may lead to 1) higher levels of homologous recombination between repeats flanking retrotransposons in dCAP-D3 deficient cells and 2) increased retrotransposition. These findings identify a novel role for the anti-pairing activities of dCAP-D3/Condensin II and uncover a new way in which dCAP-D3/Condensin II influences local

  6. Serum 25–Hydroxyvitamin D3 and Mammography Density among Mexican Women

    PubMed Central

    Amadou, Amina; Biessy, Carine; Rinaldi, Sabina; Fedirko, Veronika; Assi, Nada; Lajous, Martin; Ortiz-Panozo, Eduardo; Yunes, Elsa; Lopez-Ridaura, Ruy; Torres-Mejia, Gabriela; Romieu, Isabelle

    2016-01-01

    Low circulating levels of vitamin D and high mammographic density (MD) have been associated with higher risk of breast cancer. Although some evidence suggested an inverse association between circulating vitamin D and MD, no studies have investigated this association among Mexican women. We examined whether serum 25−hydroxyvitamin D3 [25(OH)D3] levels were associated with MD in a cross-sectional study nested within the large Mexican Teacher's Cohort. This study included 491 premenopausal women with a mean age of 42.9 years. Serum 25(OH)D3 levels were measured by liquid chromatography/tandem mass spectrometry. Linear regression and non-linear adjusted models were used to estimate the association of MD with serum 25(OH)D3. Median serum 25(OH)D3 level was 27.3 (23.3–32.8) (ng/ml). Forty one (8%) women had 25(OH)D3 levels in the deficient range (< 20 ng/ml). Body mass index (BMI) and total physical activity were significantly correlated with 25(OH)D3 (r = −0.109, P = 0.019 and r = 0.095, P = 0.003, respectively). In the multivariable linear regression, no significant association was observed between 25(OH)D3 levels and MD overall. However, in stratified analyses, higher serum 25(OH)D3 levels (≥27.3 ng/ml) were significantly inversely associated with percent MD among women with BMI below the median (β = −0.52, P = 0.047). Although no significant association was observed between serum 25(OH)D3 and percent MD in the overall population, specific subgroups of women may benefit from higher serum 25(OH)D3 levels. PMID:27564705

  7. Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle

    SciTech Connect

    Simpson, R.U.; Thomas, G.A.; Arnold, A.J.

    1985-07-25

    Cytosols from cultured myoblast cells prepared in high salt possesses receptor like proteins for 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) that sediment in the 3.2 S region of sucrose gradients. These receptors were characterized as having high affinity for 1,25-(OH)2D3 and are in low capacity. Analog competition for receptor binding revealed that 1,25-(OH)2D3 was more potent than 24,25-(OH)2D3, or 25-(OH)2D3 for displacement of 1,25-(OH)2(TH)D3 from these 3.2 S region sedimenting receptors. Furthermore, the receptor proteins had affinity for DNA and eluted from Sephacryl S-200 as a macromolecule with Stokes radius (Rs) of 32 A. High salt cytosol from collagenase-dispersed skeletal muscle cells was also found to possess a 3.2 S 1,25-(OH)2D3 receptor-like protein. The 1,25-(OH)2D3 receptor concentration was found to down-regulate by 50-70% when cells were stimulated to differentiate to myotubes by lowering fetal calf serum to 5% of the medium. Moreover, the authors demonstrated that 1,25-(OH)2D3 can inhibit DNA synthesis and cell proliferation of the G-8 myoblast cells in a dose-dependent manner. The data support the possibility that muscle is a target tissue for 1,25-(OH)2D3 and the hormone may act to initiate terminal differentiation of myoblast cells.

  8. Vitamin D3 pretreatment regulates renal inflammatory responses during lipopolysaccharide-induced acute kidney injury.

    PubMed

    Xu, Shen; Chen, Yuan-Hua; Tan, Zhu-Xia; Xie, Dong-Dong; Zhang, Cheng; Zhang, Zhi-Hui; Wang, Hua; Zhao, Hui; Yu, De-Xin; Xu, De-Xiang

    2015-01-01

    Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury. PMID:26691774

  9. Targeted delivery of 1,25-dihydroxyvitamin D3 to colon tissue and identification of a major 1,25-dihydroxyvitamin D3 glycoside from Solanumglaucophyllum plant leaves.

    PubMed

    Zimmerman, Duane R; Koszewski, Nicholas J; Hoy, Derrel A; Goff, Jesse P; Horst, Ronald L

    2015-04-01

    Leaves of the Solanum glaucophyllum (Sg) plant, indigenous to South America, have long been known for their calcinogenic toxicity in ruminant animals. It was determined the leaves contained glycosidic derivatives of 1,25-dihydroxyvitamin D3 (1,25D3) and liberation of the free hormone by rumen bacterial populations elicited a hypercalcemic response. Our interest in the leaves is predicated on the concept that the glycoside forms of 1,25D3 would target release of the active hormone in the lower gut of non-ruminant mammals. This would provide a means of delivering 1,25D3 directly to the colon, where the hormone has been shown to have beneficial effects in models of inflammatory bowel disease (IBD) and colon cancer. We fed mice for 10 days with variable amounts of Sg leaf. Feeding 7-333μg leaf/day produced no changes in plasma Ca(2+) and 1,25D3 concentrations, and only at ≥1000μg leaf/day did these values become significantly elevated compared to controls. Gene expression studies from colon tissue indicated a linear relationship between the amount of leaf consumed and expression of the Cyp24a1 gene. In contrast, Cyp24a1 gene expression in the duodenums and ileums of these mice was unchanged compared to controls. One of the major 1,25D3-glycosides was isolated from leaves following extraction and purification by Sep-Pak cartridges and HPLC fractionation. Ultraviolet absorbance was consistent with modification of the 1-hydroxyl group, and positive ion ESI mass spectrometry indicated a diglycoside of 1,25D3. 2-Dimensional NMR analyses were carried out and established the C1 proton of the A-ring was interacting with a C1' sugar proton, while the C3 proton of the A-ring was linked with a second C1' sugar proton. The structure of the isolated compound is therefore consistent with a β-linked 1,3-diglycoside of 1,25D3. Thus, Sg leaf administered to mice at up to 333 ug/day can elicit colon-specific enhancement of Cyp24a1 gene expression without inducing hypercalcemia, and

  10. 16 CFR Appendix D3 to Part 305 - Water Heaters-Oil

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Water Heaters-Oil D3 Appendix D3 to Part 305... DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER PRODUCTS REQUIRED... Part 305—Water Heaters—Oil Range Information CAPACITY FIRST HOUR RATING Range of Estimated...

  11. Comparison of analysis of vitamin D3 in foods using ultraviolet and mass spectrometric detection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    <