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Sample records for vitamin d3 up-regulated

  1. Plasma and milk concentrations of vitamin D3 and 25-hydroxy vitamin D3 following intravenous injection of vitamin D3 or 25-hydroxy vitamin D3.

    OpenAIRE

    Hidiroglou, M; Knipfel, J E

    1984-01-01

    Plasma levels of vitamin D3 or 25-hydroxyvitamin D3 in ewes after administration of a single massive intravenous dose of vitamin D3 (2 X 10(6) IU) or 25-hydroxy vitamin D3 (5 mg) were determined at zero, one, two, three, five, ten and 20 days postinjection. In six ewes injected with vitamin D3 conversion of vitamin D3 to 25-hydroxy vitamin D3 resulted in a six-fold increase in the plasma 25-hydroxy vitamin D3 level within one day. Elevated levels were maintained until day 10 but by day 20 a s...

  2. Tissue content of vitamin D3 and 25-hydroxy vitamin D3 in minipigs after cutaneous synthesis, supplementation and deprivation of vitamin D3

    DEFF Research Database (Denmark)

    Burild, Anders; Frandsen, Henrik Lauritz; Poulsen, Morten

    2015-01-01

    Information regarding the endogenous storages of vitamin D3 after cutaneous vitamin D synthesis compared to oral vitamin D3 supplementation is sparse. Furthermore it is not known whether vitamin D3 can be stored for later use during periods of shortages of vitamin D3. To investigate the endogenous...

  3. Vitamin D3 increases in abdominal subcutaneous fat tissue after supplementation with vitamin D3

    DEFF Research Database (Denmark)

    Didriksen, Allan; Burild, Anders; Jakobsen, Jette

    2015-01-01

    Objective: The objective was to assess the amount of vitamin D-3 stored in adipose tissue after long-term supplementation with high dose vitamin D-3. Design: A cross-sectional study on 29 subjects with impaired glucose tolerance who had participated in a randomized controlled trial with vitamin D-3...... 20 000 IU (500 mu g) per week vs placebo for 3-5 years. Methods: Abdominal subcutaneous fat tissue was obtained by needle biopsy for the measurements of vitamin D-3 and 25-hydroxyvitamin D-3 (25(OH)D-3). Body fat was measured with dual-energy X-ray absorptiometry, and serum 25(OH)D-3 level...... was quantified. Results: In the subjects given vitamin D-3, the median concentrations of serum 25(OH)D-3, fat vitamin D-3, and fat 25(OH)D-3 were 99 nmol/l, 209 ng/g, and 3.8 ng/g, respectively; and correspondingly in the placebo group 62 nmol/l, 32 ng/g, and 2.5 ng/g. If assuming an equal amount of vitamin D-3...

  4. VITAMIN D3: RESEARCH BREAKTHROUGHS AND THERAPEUTIC USE

    Directory of Open Access Journals (Sweden)

    Pohorila М.S.

    2017-12-01

    Full Text Available Vitamin D3 (cholecalciferol, the natural form of vitamin D, is produced in the skin from 7-dehydrocholesterol. The synthesis of vitamin D in the skin is the most important source of vitamin D. Vitamin D can also be taken through nutrition, in the diet, but it is present in only a few food sources, containing relevant levels of vitamin D. 1,25-dihydroxyvitamin D3 [1,25(OH2D3] is the hormonally active form of vitamin D. Novel researches show it generates a number of extraskeletal biological responses including inhibition of variety types cancer progression, effects on cardiovascular disorders and mediates a protection against a number of inflammatory, autoimmune and infection diseases The biological actions of 1,25(OH2D3 are mediated by the VDR. The genomic mechanism of 1,25(OH2D3 action involves the direct binding of 1,25(OH2D3 activated VDR/RXR to specific DNA sequences in and around target genes resulting in either activation or repression of transcription [7] VDR modulates the expression of genes involved in immune function and cytokine production. The VDR and CYP27B1, the enzyme located in kidneys and target organs, are present in immune competent cells, bronchial and pulmonary epithelial cells, among others, and is up-regulated following the ligation of specific toll-like receptors by extracellular pathogens, implicating vitamin D in innate immunity. By binding the VDR, calcitriol induces several endogenous antimicrobial peptides (AMP in monocytes, neutrophils and epithelial cells including cathelicidin LL-37, α-defensin, β defensing and neutrophil gelatinase-associated lipocalin and up-regulates nitric oxide (NO synthase. Since the inflammatory response associated with infections such influenza, pneumonia and sepsis increases both clinical severity and mortality, the ability to reduce inflammation may allow vitamin D to decrease mortality and disease burden in certain infections. Notwithstanding the width of possible vitamin D application

  5. Novel Gemini vitamin D3 analogs

    DEFF Research Database (Denmark)

    Okamoto, Ryoko; Gery, Sigal; Kuwayama, Yoshio

    2014-01-01

    We have synthesized 39 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] analogs having two side chains attached to carbon-20 (Gemini) with various modifications and compared their anticancer activities. Five structure-function rules emerged to identify analogs with enhanced anticancer activity. One...... of these active analogs, BXL-01-0126, was more potent than 1,25(OH)2D3 in mediating 50% clonal inhibition of cancer cell growth. Murine studies found that BXL-01-0126 and 1,25(OH)2D3 had nearly the same potency to raise serum calcium levels. Taken together, BXL-01-0126 when compared to 1,25(OH)2D3 has greater...... anticancer potency, but similar toxicity causing hypercalcemia. We focused on the effect of these compounds on the stimulation of expression of human cathelicidin antimicrobial peptide (CAMP) whose gene has a vitamin D response element in its promoter. Expression of CAMP mRNA and protein increased in a dose...

  6. Translating the role of vitamin D3 in infectious diseases.

    NARCIS (Netherlands)

    Khoo, A.L.; Chai, L.; Koenen, H.J.; Joosten, I.; Netea, M.G.; Ven, A. van der

    2012-01-01

    Vitamin D(3) affects both the innate as well as adaptive immune responses. Epidemiological studies have established that vitamin D(3) deficiency plays an important role in tuberculosis (TB) and viral influenza prevalence as well as susceptibility to active disease in TB. Vitamin D(3) status has been

  7. 21 CFR 582.5953 - Vitamin D3.

    Science.gov (United States)

    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 generally...

  8. Regulation of the vitamin D receptor and cornifin beta expression in vaginal epithelium of the rats through vitamin D3

    Directory of Open Access Journals (Sweden)

    G Abban

    2009-08-01

    Full Text Available The aim of the present study was to determine the respective role of 1,25-dihydroxyvitamin D3 on vaginal epithelium and 1,25-dihydroxyvitamin D3 receptor expression in ovariectomized rats and vitamin D3 treated rats. Bilateral ovariectomies were performed in 20 mature, non-pregnant Wistar female rats. All the animals were divided into 2 groups consisting of 10 rats each. Group I served as control. In group II, animals were injected intramuscularly with vitamin D3 (50, 00 IU/kg. Two weeks after the injections, vaginas of animals in group I and group II were removed removed and processed for immunohistochemistry. Epithelial differentiation, 1,25-dihydroxyvitamin D3 receptor and cornifin b expression were investigated in vaginal epithelium of control group (ovariectomized and vitamin D3 treated rats. Vaginal epithelial cells from vitamin D3 treated animals changed into highly- stratified keratinizing layers. 1,25-dihydroxyvitamin D3 receptor and cornifin b as a marker of squamous differentiation were present in ovariectomized rats treated with 1,25- dihydroxyvitamin D3. In contrast, cornifin b and 1,25-dihydroxyvitamin D3 receptor were absent in all layers of vaginal epithelium in control group. We demonstrated for the first time that 1,25-dihydroxyvitamin D3 induced proliferation of vaginal epithelium consistent with the cornifin b expression and 1,25-dihydroxyvitamin D3 up-regulated 1,25-dihydroxyvitamin D3 receptor expression in vaginal epithelium.

  9. Vitamin D3 a new drug against Candida albicans.

    Science.gov (United States)

    Bouzid, D; Merzouki, S; Bachiri, M; Ailane, S E; Zerroug, M M

    2017-03-01

    In this study, we demonstrate that vitamin D3 had fungicidal activity against Candida albicans. The susceptibility of the yeast strain to the vitamin D3 was investigated by the antimicrobial screening using modified agar diffusion method, minimum fungistatic concentrations (MFCs) and minimum fungicide concentrations (MFCC) of the vitamin D3 were determined by the broth dilution method. The antifungal activity indicted that 100μg/ml of vitamin D3 had a power inhibition in the growth of C. albicans with zone of inhibition 12.5mm and CMFC and CMFs were 1.58±0.0764μg/ml. These values indicate that vitamin D3 can be considered to have fungicide activity. This antifungal effect may be due to the large lipsolubility of vitamin D3 changing the integrity of the cell membrane. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Vitamin D up-regulates the vitamin D receptor by protecting it from proteasomal degradation in human CD4+ T cells

    DEFF Research Database (Denmark)

    Kongsbak, Martin; von Essen, Marina R; Boding, Lasse

    2014-01-01

    The active form of vitamin D3, 1,25(OH)2D3, has significant immunomodulatory properties and is an important determinant in the differentiation of CD4+ effector T cells. The biological actions of 1,25(OH)2D3 are mediated by the vitamin D receptor (VDR) and are believed to correlate with the VDR...... protein expression level in a given cell. The aim of this study was to determine if and how 1,25(OH)2D3 by itself regulates VDR expression in human CD4+ T cells. We found that activated CD4+ T cells have the capacity to convert the inactive 25(OH)D3 to the active 1,25(OH)2D3 that subsequently up......-regulates VDR protein expression approximately 2-fold. 1,25(OH)2D3 does not increase VDR mRNA expression but increases the half-life of the VDR protein in activated CD4+ T cells. Furthermore, 1,25(OH)2D3 induces a significant intracellular redistribution of the VDR. We show that 1,25(OH)2D3 stabilizes the VDR...

  11. Treatment of vitiligo vulgaris with the combination therapy of topical steroid and vitamin D3 compound

    Directory of Open Access Journals (Sweden)

    Yoko Konishi

    2012-06-01

    Full Text Available We reported here two cases of vitiligo vulgaris successfully treated with the combination therapy of topical steroid and vitamin D3 compound and currently maintained by vitamin D3 analog without any adverse effects: skin atrophy, striae or telangiectasia on the exposed areas. The best-known mechanism of topical vitamin D3 analog is the enhancement of keratinocytes differentiation and anti-proliferative effects. Vitamin D3 analog is also reported to suppress T-cell mediated immunity, T-cell skin recruitment, and skin infiltration via down-regulating cutaneous lymphocyte antigen expression. Furthermore, vitamin D3 compounds are known to influence melanocyte maturation and differentiation and also to up-regulate melanogenesis. Autoreactive lymphocytes against melanocytes are one of the causes. Topical vitamin D3 analog may control vitiligo itself, however stronger immunosuppressive effects of topical corticosteroid may contribute to rapid re-pigmentation suppressing auto-reactive lymphocytes. The topical combination therapy is a simple, effective and safe option for vitiligo vulgaris in sun-exposed areas.

  12. Translating the role of vitamin D3 in infectious diseases.

    Science.gov (United States)

    Khoo, Ai Leng; Chai, Louis; Koenen, Hans; Joosten, Irma; Netea, Mihai; van der Ven, André

    2012-05-01

    Vitamin D(3) affects both the innate as well as adaptive immune responses. Epidemiological studies have established that vitamin D(3) deficiency plays an important role in tuberculosis (TB) and viral influenza prevalence as well as susceptibility to active disease in TB. Vitamin D(3) status has been associated with the clinical course of HIV infection and drug interaction with anti-retroviral therapy. This article reviews the immunomodulatory capacity of vitamin D(3) and examines the impact of vitamin D(3) supplementation as a preventive or therapeutic intervention with the intent to uncover its potential therapeutic application in infectious diseases and to identify novel areas for future research. We present a review of randomized, controlled clinical studies conducted in humans which included assessment of the immune function or clinical outcome as study end points. Current data support vitamin D(3) supplementation as risk-modifying intervention in tuberculosis and viral respiratory tract infection, but the optimal dosage regimen remains to be determined. However, to date the knowledge on its role in fungal infection and sepsis is limited although a potential benefit could be harnessed from its ability to curtail the unrestrained pro-inflammatory response and therefore prevent excessive collateral tissue damage.

  13. A new method for the determination of vitamin D-3 and 25-hydroxyvitamin D-3 in meat

    DEFF Research Database (Denmark)

    Jakobsen, Jette; Clausen, I.; Leth, Torben

    2004-01-01

    D-2 was used as internal standard for vitamin D-3 as well as for 25-hydroxyvitamin D-3. Precision for vitamin D-3 was determined in lean meat and lard to 9.1% and 7.1%, respectively. The corresponding values for 25-hydroxyvitamin D-3 were 8.9% and 9.9%. Accuracy was determined in spiked samples...

  14. 25-Hydroxyvitamin D-3 affects vitamin D status similar to vitamin D-3 in pigs - but the meat produced has a lower content of vitamin D

    DEFF Research Database (Denmark)

    Jakobsen, Jette; Maribo, H.; Bysted, Anette

    2007-01-01

    In food databases, the specific contents of vitamin D-3 and 25-hydroxyvitamin D-3 in food have been implemented in the last 10 years. No consensus has yet been established on the relative activity between the components. Therefore, the objective of the present study was to assess the relative...... activity of 25-hydroxyvitamin D-3 compared to vitamin D-3. The design was a parallel study in pigs (n 24), which from an age of 12 weeks until slaughter 11 weeks later were fed approximately 55 mu g vitamin D/d, as vitamin D-3, in a mixture of vitamin D-3 and 25-hydroxyvitamin D-3, or 25-hydroxyvitamin D-3...

  15. How much vitamin D-3 do the elderly need?

    DEFF Research Database (Denmark)

    Viljakainen, H.T.; Palssa, A.; Karkkainen, M.

    2006-01-01

    parathyroid hormone, (S-iPTH) concentrations. Aims of the Study: We studied how serum 25-hydroxy vitamin D (S-25-OHD) concentrations respond to different doses of vitamin D3 supplementation. Secondly to determine the smallest efficient dose to maintain serum 25-OHD concentration above the insufficiency level...... with increasing vitamin D supplementation. The dose-response to supplementation decreased with increasing vitamin D status at baseline, r = -0.513, p = 0.002. S-iPTH tended to decrease in those with highest dose response to supplementation. Conclusions: A clear dose response was noted in S-25-OHD to different......Background: Vitamin D insufficiency poses a problem in many parts of the world, the elderly being an especially vulnerable group. This insufficiency results from an inadequate amount of sunshine and a low dietary intake of vitamin D. Typically, insufficiency is accompanied with high intact...

  16. Vitamin D3 and calcidiol are not equipotent.

    Science.gov (United States)

    Navarro-Valverde, Cristina; Sosa-Henríquez, Manuel; Alhambra-Expósito, Maria Rosa; Quesada-Gómez, José Manuel

    2016-11-01

    Despite the discussion on the optimal threshold of 25-hydroxyvitamin D serum level continues, there is now consensus on the fact that post-menopausal and elderly populations have inadequate Vitamin D serum levels worldwide. The adjustment of these levels is necessary to improve both bone and general health, as it is to optimize bone response to antiresortive treatments. It is recommended, as endorsed by international clinical guides, to use Vitamin D3, the physiological form of Vitamin D, in a dose range between 600-2000IU. It should be administered on a daily basis or on its weekly or monthly equivalents. In Spain, the use of calcidiol (25(OH)D3) at the same dose than Vitamin D3 is the most extended prescription, notwithstanding the available evidence stating that they are not equipotent. This may lead to over-dosage. In order to provide evidence on this circumstance, a convenience study was performed. Four groups of ten post-menopausal osteoporotic women each (average age 67), deficient in Vitamin D ((25(OH)D 37.5±10 nmol/L)) were enrolled. Each group followed a different treatment regimen: (G1) vitamin D3 20μg/day [800IU/day]; (G2) 25 (OH)D3 20μg/day; (G3) 25(OH)D3 266μg/week and (G4) 25(OH)D3 0.266mg every two weeks. 25(OH)D levels were measured for each group at 0, 6 and 12 months, with the following results: G1 (40.5±4.7;80.0±2; 86.2±23.7), G2 (37,2±4.2; 161±21.7;188.0±24.0), G3 (38±3.7;213.5±80.0; 233.0±81.2), G4 (39.5±4;164.5±41,7;210.5±22.2). These data reveal that both metabolites are not equipotent. Calcidiol is faster and 3-6 times more potent to obtain serum levels of 25(OH)D in the medium to long term. This circumstance must be assessed and included in the therapeutic prescription guides for Osteoporosis, since it should be of concern when planning and prescribing treatments to normalize serum levels of 25(OH)D3 and avoid potential adverse impacts. Copyright © 2016. Published by Elsevier Ltd.

  17. 1α,25-dihydroxyvitamin D3 acts via transforming growth factor-β to up-regulate expression of immunosuppressive CD73 on human CD4+ Foxp3- T cells.

    Science.gov (United States)

    Mann, Elizabeth H; Chambers, Emma S; Chen, Yin-Huai; Richards, David F; Hawrylowicz, Catherine M

    2015-11-01

    Vitamin D deficiency is associated with increased incidence and severity of various immune-mediated diseases. Active vitamin D (1α,25-dihydroxyvitamin D3; 1,25(OH)2 D3) up-regulates CD4(+) T-cell expression of the purine ectonucleotidase CD39, a molecule that is associated with the generation of anti-inflammatory adenosine. Here we aimed to investigate the direct impact of 1,25(OH)2 D3 on expression of the downstream ecto-5'-nucleotidase CD73 by human CD4 T cells, and components of the transforming growth factor-β (TGF-β) pathway, which have been implicated in the modulation of CD73 by murine T cells. At 10(-8) to 10(-7) m, 1,25(OH)2 D3 significantly increased expression of CD73 on peripheral human CD4(+) T cells. Although 1,25(OH)2 D3 did not affect the mRNA expression of latent TGF-β1 , 1,25(OH)2 D3 did up-regulate expression of TGF-β-associated molecules [latency-associated peptide (LAP), glycophorin A repetitions predominant (GARP), GP96, neuropilin-1, thrombospondin-1 and αv integrin] which is likely to have contributed to the observed enhancement in TGF-β bioactivity. CD73 was highly co-expressed with LAP and GARP following 1,25(OH)2 D3 treatment, but unexpectedly, each of these cell surface molecules was expressed primarily on CD4(+) Foxp3(-) T cells, rather than CD4(+) Foxp3(+) T cells. Notably, neutralization of TGF-β significantly impaired 1,25(OH)2 D3-mediated induction of CD73. Collectively, we show that 1,25(OH)2 D3 enhances expression of CD73 on CD4(+) Foxp3(-) T cells in a process that is at least partially TGF-β-dependent. These data reveal an additional contributing mechanism by which vitamin D may be protective in immune-mediated disease. © 2015 John Wiley & Sons Ltd.

  18. 1-alpha,25-Dihydroxyvitamin D3 up-regulates the expression of 2 types of human intestinal alkaline phosphatase alternative splicing variants in Caco-2 cells and may be an important regulator of their expression in gut homeostasis.

    Science.gov (United States)

    Noda, Seiko; Yamada, Asako; Nakaoka, Kanae; Goseki-Sone, Masae

    2017-10-01

    Vitamin D insufficiency is associated with a greater risk of osteoporosis and also influences skeletal muscle functions, differentiation, and development. The principal function of vitamin D in calcium homeostasis is to increase the absorption of calcium from the intestine, and the level of alkaline phosphatase (ALP) activity, a differentiation marker for intestinal epithelial cells, is regulated by vitamin D. Intestinal-type ALP is expressed at a high concentration in the brush border membrane of intestinal epithelial cells, and is known to be affected by several kinds of nutrients. Recent reviews have highlighted the importance of intestinal-type ALP in gut homeostasis. Intestinal-type ALP controls bacterial endotoxin-induced inflammation by dephosphorylating lipopolysaccharide and is a gut mucosal defense factor. In this study, we investigated the influence of vitamin D on the expression of 2 types of alternative mRNA variants encoding the human alkaline phosphatase, intestinal (ALPI) gene in human Caco-2 cells as an in vitro model of the small intestinal epithelium. After treatment with 1-alpha,25-dihydroxyvitamin D3, the biologically active form of vitamin D3, there were significant increases in the ALP activities of Caco-2 cells. Inhibitor and thermal inactivation experiments showed that the increased ALP had properties of intestinal-type ALP. Reverse transcription-polymerase chain reaction analysis revealed that expression of the 2 types of alternative mRNA variants from the ALPI gene was markedly enhanced by vitamin D in Caco-2 cells. In conclusion, these findings agree with the hypothesis: vitamin D up-regulated the expression of 2 types of human intestinal alkaline phosphatase alternative splicing variants in Caco-2 cells; vitamin D may be an important regulator of ALPI gene expression in gut homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. 25(OH)D3-enriched or fortified foods are more efficient at tackling inadequate vitamin D status than vitamin D3.

    Science.gov (United States)

    Guo, Jing; Lovegrove, Julie A; Givens, D Ian

    2017-11-27

    The ability to synthesise sufficient vitamin D through sunlight in human subjects can be limited. Thus, diet has become an important contributor to vitamin D intake and status; however, there are only a few foods (e.g. egg yolk, oily fish) naturally rich in vitamin D. Therefore, vitamin D-enriched foods via supplementing the animals' diet with vitamin D or vitamin D fortification of foods have been proposed as strategies to increase vitamin D intake. Evidence that cholecalciferol (vitamin D3) and calcifediol (25(OH)D3) content of eggs, fish and milk increased in response to vitamin D3 supplementation of hens, fish or cows' diets was identified when vitamin D-enrichment studies were reviewed. However, evidence from supplementation studies with hens showed only dietary 25(OH)D3, not vitamin D3 supplementation, resulted in a pronounced increase of 25(OH)D3 in the eggs. Furthermore, evidence from randomised controlled trials indicated that a 25(OH)D3 oral supplement could be absorbed faster and more efficiently raise serum 25(OH)D concentration compared with vitamin D3 supplementation. Moreover, evidence showed the relative effectiveness of increasing vitamin D status using 25(OH)D3 varied between 3·13 and 7·14 times that of vitamin D3, probably due to the different characteristics of the investigated subjects or study design. Therefore, vitamin D-enrichment or fortified foods using 25(OH)D3 would appear to have advantages over vitamin D3. Further well-controlled studies are needed to assess the effects of 25(OH)D3 enriched or fortified foods in the general population and clinical patients.

  20. Vitamin D2 versus vitamin D3 supplementation in hemodialysis patients: a comparative pilot study.

    Science.gov (United States)

    Daroux, Maïté; Shenouda, Milhad; Bacri, Jean-Louis; Lemaitre, Vincent; Vanhille, Philippe; Bataille, Pierre

    2013-01-01

    In patients with chronic kidney disease, vitamin D insufficiency is highly prevalent. It can be corrected by supplementation with either vitamin D(2) or vitamin D3. Recent studies in patients without impaired kidney function suggest that vitamin D(3) is more efficient than vitamin D(2) in correcting vitamin D insufficiency. However, no direct comparison has been made in hemodialysis (HD) patients. Thirty-nine HD patients with serum 25-hydroxyvitamin D (25(OH)D) levels =20 ng/mL were enrolled in this comparative, prospective pilot study. They were divided into 3 groups and treated over a 3-month period. Each patient received oral doses of 200,000 international units (IU) vitamin D per month according to the following treatment schedule: (i) vitamin D(2) in small fractionated doses at each HD session, 3 times per week (group D2S); (ii) vitamin D(2) once a month (group D2M); or (iii) vitamin D(3) once a month (group D3M). Changes in serum 25(OH)D levels were measured at the end of the study. Posttreatment serum 25(OH)D levels increased significantly in all groups. The mean ± SD serum 25(OH)D value for group D3M patients (40 ± 13 ng/mL) was significantly higher than that for groups D2M (25 ± 9 ng/mL, p30 ng/mL in 84% of group D3M patients, but in only 15% and 27% of group D2M and D2S subjects, respectively. Vitamin D(3) is more effective than vitamin D(2) in providing adequate 25(OH)D serum levels in HD patients.

  1. Antidepressants differentially related to 1,25-(OH)(2) vitamin D(3) and 25-(OH) vitamin D(3) in late-life depression

    NARCIS (Netherlands)

    Oude Voshaar, R.C.; Derks, W.J.; Comijs, H.C.; Schoevers, R.A.; Borst, M.H. de; Marijnissen, R.M.

    2014-01-01

    A low plasma 25-OH vitamin D3 level is a universal risk factor for a wide range of diseases and has also been implicated in late-life depression. It is currently unknown whether the biologically active form of vitamin D, that is, 1,25-(OH)2 vitamin D3, is also decreased in late-life depression, or

  2. Vitamin D3 analogs for the treatment of osteoporosis.

    Science.gov (United States)

    Hagino, Hiroshi

    2015-05-01

    Vitamin D supplementation is recommended whenever patients are given therapeutic drugs for osteoporosis, to make their calcium (Ca) balance positive. Vitamin D is converted to 25-hydroxyvitamin D in the liver, and then activated to become 1α,25-dihydroxyvitamin D in the kidneys. The active vitamin D acts in the intestine to stimulate Ca absorption and maintain the Ca balance. 2β-(3-Hydroxypropyloxy)-1α,25-dihydroxyvitamin D3 (eldecalcitol) and 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD) are newly developed vitamin D analogs, with a substitution at the 2 position of 1α,25-dihydroxyvitamin D3 (calcitriol). Eldecalcitol and 2MD share common structural and biological characteristics. Both compounds increase serum Ca levels more markedly than calcitriol, increase bone mineral density (BMD), and improve bone strength in ovariectomized (OVX) rats. In a randomized, placebo-controlled, double-blind, 1 year clinical trial, eldecalcitol dose-dependently increased lumbar and hip BMD and suppressed bone turnover markers in patients with osteoporosis. Whereas, 2MD markedly increased the bone turnover markers, but it did not change the BMD of postmenopausal women with osteopenia in a 1 year clinical trial. After a randomized, double-blind, 3 year fracture-prevention trial comparing it with alfacalcidol, eldecalcitol was approved for the treatment of osteoporosis in Japan. On the other hand, the manufacturer discontinued the clinical development of 2MD. In this review, we discuss the similarities and differences between these 2 compounds, and the reasons why different outcomes resulted from their clinical trials.

  3. [Influence of active vitamine D3 on bones (author's transl)].

    Science.gov (United States)

    Kaneko, N

    1979-12-01

    Influence of 1 alpha-OH-D3, an active vitamine D supplement, on bone cells was studied, histologically and electro-microscopically observing the vitamine D objective bone cell after treatment with the drug in a dose of 50 microgram/kg/day. Light-microscopic findings revealed that osteogenesis gradually became dominant after transient osteoporosis, leading to a disproportional state of the bone remodelling. In electromicroscopy, no morphological changes were observed, though the number of osteoclasts increased five days after treatment. Hypofunctional findings, however, appeared seven and ten days after treatment. On the other hand, findings of distinguishable osteogenesis, e.g. well-developed golgi complex (G), endoplasmic reticulum (ER), mitochondria (M), were observed in the osteoblast and osteocyte, defining the strong influence of vitamine D in a large dose on the osteoblast-osteocyte system. Especially, the osteoblast seemed to be influenced earlier and to a greater degree. We concluded that 1 alpha-OH-D3 in doses of 0.02 and 0.08 microgram/kg/day hardly caused any morphological changes in the bone cell in our experiment.

  4. Identification of vitamin D3 target genes in human breast cancer tissue.

    Science.gov (United States)

    Sheng, Lei; Anderson, Paul H; Turner, Andrew G; Pishas, Kathleen I; Dhatrak, Deepak J; Gill, Peter G; Morris, Howard A; Callen, David F

    2016-11-01

    Multiple epidemiological studies have shown that high vitamin D3 status is strongly associated with improved breast cancer survival. To determine the molecular pathways influenced by 1 alpha, 25-dihydroxyvitamin D3 (1,25D) in breast epithelial cells we isolated RNA from normal human breast and cancer tissues treated with 1,25D in an ex vivo explant system. RNA-Seq revealed 523 genes that were differentially expressed in breast cancer tissues in response to 1,25D treatment, and 127 genes with altered expression in normal breast tissues. GoSeq KEGG pathway analysis revealed 1,25D down-regulated cellular metabolic pathways and enriched pathways involved with intercellular adhesion. The highly 1,25D up-regulated target genes CLMN, SERPINB1, EFTUD1, and KLK6were selected for further analysis and up-regulation by 1,25D was confirmed by qRT-PCR analysis in breast cancer cell lines and in a subset of human clinical samples from normal and cancer breast tissues. Ketoconazole potentiated 1,25D-mediated induction of CLMN, SERPINB1, and KLK6 mRNA through inhibition of 24-hydroxylase (CYP24A1) activity. Elevated expression levels of CLMN, SERPINB1, and KLK6 are associated with prolonged relapse-free survival for breast cancer patients. The major finding of the present study is that exposure of both normal and malignant breast tissue to 1,25D results in changes in cellular adhesion, metabolic pathways and tumor suppressor-like pathways, which support epidemiological data suggesting that adequate vitamin D3 levels may improve breast cancer outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Vitamin D supplementation up-regulates IL-6 and IL-17A gene expression in multiple sclerosis patients.

    Science.gov (United States)

    Naghavi Gargari, Bahar; Behmanesh, Mehrdad; Shirvani Farsani, Zeinab; Pahlevan Kakhki, Majid; Azimi, Amir Reza

    2015-09-01

    Vitamin D regulates gene expression and affects target cell functions. IL-6 and IL-17A are pro-inflammatory cytokines associated with MS pathogenesis. The aim of this study was to investigate the vitamin D effects on the expression level of IL-6 and IL-17A in peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients. Also, we performed a correlation analysis between the gene expression and some clinical features such as serum level of vitamin D and the expanded disability status scale (EDSS). Significant up-regulation of IL-6 and IL-17A gene expression was shown under vitamin D treatment. Also, some gender specific correlations between the gene expression with vitamin D levels were detected in female RR-MS patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Vitamin D3 synthesis in the entire skin surface of dairy cows despite hair coverage

    DEFF Research Database (Denmark)

    Hymøller, Lone; Jensen, Søren Krogh

    2010-01-01

    synthesis in the skin during exposure to sunlight. Different scenarios have been suggested but never tested in cows; for example, that vitamin D3 is synthesized from sebum on the hair and ingested by cows during grooming or that body areas such as the udder and muzzle that have scant hair exclusively...... hair are not comparable with respect to prevention of vitamin D3 synthesis and that cows, like humans, synthesize vitamin D3 evenly over their body surface. That vitamin D3 should be synthesized from sebum on the hair and obtained by cows as a result of grooming is not supported by the findings......How hair-coated animals such as dairy cows synthesize endogenous vitamin D3 during exposure to summer sunlight has been unclear since vitamin D3 and its relation to sunlight was discovered. The fur of fur-bearing animals is thought to be comparable to clothing in humans, which prevents vitamin D3...

  7. Effect of Vitamin D3 Supplementation During Pregnancy on Risk of Persistent Wheeze in the Offspring: A Randomized Clinical Trial.

    Science.gov (United States)

    Chawes, Bo L; Bønnelykke, Klaus; Stokholm, Jakob; Vissing, Nadja H; Bjarnadóttir, Elín; Schoos, Ann-Marie M; Wolsk, Helene M; Pedersen, Tine Marie; Vinding, Rebecca K; Thorsteinsdóttir, Sunna; Arianto, Lambang; Hallas, Henrik W; Heickendorff, Lene; Brix, Susanne; Rasmussen, Morten A; Bisgaard, Hans

    2016-01-26

    Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of vitamin D supplementation to pregnant women is unknown. To determine whether supplementation of vitamin D3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring. A double-blind, single-center, randomized clinical trial conducted within the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. Enrollment began March 2009 with a goal of 708 participants, but due to delayed ethical approval, only 623 women were recruited at 24 weeks of pregnancy. Follow-up of the children (N = 581) was completed when the youngest child reached age 3 years in March 2014. Vitamin D3 (2400 IU/d; n = 315) or matching placebo tablets (n = 308) from pregnancy week 24 to 1 week postpartum. All women received 400 IU/d of vitamin D3 as part of usual pregnancy care. Age at onset of persistent wheeze in the first 3 years of life. Secondary outcomes included number of episodes of troublesome lung symptoms, asthma, respiratory tract infections, and neonatal airway immunology. Adverse events were assessed. Of the 581 children, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16%) in the vitamin D3 group and 57 children (20%) in the control group. Vitamin D3 supplementation was not associated with the risk of persistent wheeze, but the number of episodes of troublesome lung symptoms was reduced, and the airway immune profile was up-regulated (principal component analysis, P = .04). There was no effect on additional end points. Intrauterine death was observed in 1 fetus (interpretation of the study is limited by a wide CI that includes a clinically important protective effect. clinicaltrials.gov Identifier: NCT00856947.

  8. Efficacy and safety of vitamin D3 B.O.N intramuscular injection in Korean adults with vitamin D deficiency

    Directory of Open Access Journals (Sweden)

    Han Seok Choi

    2016-12-01

    Conclusion: Intramuscular injection of vitamin D3 200,000 IU was superior to placebo in terms of its impact on serum 25(OHD concentrations, and is considered to be safe and effective in Korean adults with vitamin D deficiency.

  9. Vitamin D3 in the hemolymph of goliath birdeater spiders (Theraphosa blondi).

    Science.gov (United States)

    Zachariah, Trevor T; Mitchell, Mark A

    2009-06-01

    Vitamin D3 is an important vitamin in vertebrates. This fat-soluble vitamin is associated with the regulation of many physiologic processes, most importantly calcium metabolism. The presence or importance of vitamin D3 has been determined in only a handful of invertebrate species. In this study, hemolymph was collected from six wild-caught, subadult goliath birdeater spiders (Theraphosa blondi) and analyzed for the presence of 25(OH)-vitamin D3, the precursor to the active form of vitamin D3. The metabolite 25(OH)-vitamin D3 was detected in all of the spiders (mean: 5.7 nmol/L, SD: 1.5 nmol/L, range: 3-7 nmol/L). The method by which spiders acquire vitamin D3 is unknown. It is possible, though unlikely, that they synthesize it via exposure to ultraviolet radiation. Many of the invertebrate species upon which theraphosid spiders prey are not known to have high circulating levels of vitamin D3 or its precursors. However, dietary intake is a possible means of vitamin D3 acquisition in this study.

  10. Expression of Inducible Nitric Oxide Synthase is Up-Regulated by Production of 1,25-Dihydroxyvitamin D3 in Bovine Monocytes in Response to Toll-Like Receptor Signaling

    Science.gov (United States)

    In the endocrine pathway of vitamin D signaling 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is produced from 25-hydroxyvitamin D3 [25(OH)D3] by the enzyme CYP27B1 in the kidney. Production of 1,25(OH)2D3 in the kidney functions to regulate gene expression systemically. However, recent studies have show...

  11. Vitamin D receptor gene is epigenetically altered and transcriptionally up-regulated in multiple sclerosis.

    Science.gov (United States)

    Ayuso, Teresa; Aznar, Patricia; Soriano, Luis; Olaskoaga, Ander; Roldán, Miren; Otano, María; Ajuria, Iratxe; Soriano, Gerardo; Lacruz, Francisco; Mendioroz, Maite

    2017-01-01

    Vitamin D deficiency has been linked to increased risk of multiple sclerosis (MS) and poor outcome. However, the specific role that vitamin D plays in MS still remains unknown. In order to identify potential mechanisms underlying vitamin D effects in MS, we profiled epigenetic changes in vitamin D receptor (VDR) gene to identify genomic regulatory elements relevant to MS pathogenesis. Human T cells derived from whole blood by negative selection were isolated in a set of 23 relapsing-remitting MS (RRMS) patients and 12 controls matched by age and gender. DNA methylation levels were assessed by bisulfite cloning sequencing in two regulatory elements of VDR. mRNA levels were measured by RT-qPCR to assess changes in VDR expression between patients and controls. An alternative VDR promoter placed at exon 1c showed increased DNA methylation levels in RRMS patients (median 30.08%, interquartile range 19.2%) compared to controls (18.75%, 9.5%), p-valuemultiple sclerosis, and it is associated with VDR mRNA upregulation. This locus may represent a candidate regulatory element in the genome relevant to MS pathogenesis.

  12. Vitamin D receptor gene is epigenetically altered and transcriptionally up-regulated in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Teresa Ayuso

    Full Text Available Vitamin D deficiency has been linked to increased risk of multiple sclerosis (MS and poor outcome. However, the specific role that vitamin D plays in MS still remains unknown. In order to identify potential mechanisms underlying vitamin D effects in MS, we profiled epigenetic changes in vitamin D receptor (VDR gene to identify genomic regulatory elements relevant to MS pathogenesis.Human T cells derived from whole blood by negative selection were isolated in a set of 23 relapsing-remitting MS (RRMS patients and 12 controls matched by age and gender. DNA methylation levels were assessed by bisulfite cloning sequencing in two regulatory elements of VDR. mRNA levels were measured by RT-qPCR to assess changes in VDR expression between patients and controls.An alternative VDR promoter placed at exon 1c showed increased DNA methylation levels in RRMS patients (median 30.08%, interquartile range 19.2% compared to controls (18.75%, 9.5%, p-value<0.05. Moreover, a 6.5-fold increase in VDR mRNA levels was found in RRMS patients compared to controls (p-value<0.001.An alternative promoter of the VDR gene shows altered DNA methylation levels in patients with multiple sclerosis, and it is associated with VDR mRNA upregulation. This locus may represent a candidate regulatory element in the genome relevant to MS pathogenesis.

  13. Effect of dietary vitamin D 3 supplementation on meat quality of ...

    African Journals Online (AJOL)

    A quadratic equation was used to determine vitamin D3 supplementation levels for optimum shear force value and sensory attributes. Vitamin D3 supplementation did not improve (P>0.05) shear force values of unaged or aged raw and cooked naked neck chicken meat. Shear force values of unaged raw or cooked meat ...

  14. Combined effects of aspirin and vitamin D3 on two OSCC cell lines: a preliminary study.

    Science.gov (United States)

    Xiao, Ting-Ting; Li, Xian; Feng, Jia-Li; Li, Yong

    2018-01-18

    We evaluated the potential effects of aspirin combined with vitamin D3 on cell proliferation and apoptosis in oral cancer cells. Compared to the untreated control or individual drug, the combinations of aspirin and vitamin D3 significantly decreased the rates of cell proliferation by CCK-8 assay, and caused higher rates of cell apoptosis in both CAL-27 and SCC-15 cells by Annexin V-FITC apoptosis assay and flow cytometry. Remarkably, the combined treatment with aspirin and vitamin D3 significantly suppressed the expression of Bcl-2 protein and p-Erk1/2 protein, examined by western blot analysis. Our study demonstrates that aspirin and vitamin D3 have biological activity against two human OSCC cell lines and their activity is synergistic or additive when two drugs used in combination with therapeutic concentrations. The combination of aspirin and vitamin D3 may be an effective approach for inducing cell death in OSCC.

  15. Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder

    NARCIS (Netherlands)

    Feng, J.; Shan, L.; Du, L.; Li, H.; Wang, W.; Wang, T.; Dong, H.; Yue, X.; Xu, Z.; Staal, W.G.; Jia, F.

    2017-01-01

    OBJECTIVE: High prevalence of vitamin D deficiency was previously reported in children with Autism Spectrum Disorder (ASD), but little is known about the efficacy of vitamin D3 treatment in ASD, although data from pilot studies seem promising. We hypothesized that serum vitamin D levels are reduced

  16. Vitamin D3 supplementation in multiple sclerosis: Symptoms and biomarkers of depression.

    Science.gov (United States)

    Rolf, Linda; Muris, Anne-Hilde; Bol, Yvonne; Damoiseaux, Jan; Smolders, Joost; Hupperts, Raymond

    2017-07-15

    Depressive symptoms are common in multiple sclerosis (MS), and both depression and MS have been associated with a poor vitamin D status. As cytokine-mediated inflammatory processes play a role in the pathogenesis of both disorders, we hypothesized that vitamin D3 supplementation reduces depressive symptoms in MS via its immunomodulatory properties. In this randomized pilot study relapsing remitting (RR) MS patients received either vitamin D3 supplementation (n=20; 14.000IU/day) or placebo (n=20) during 48weeks. Pre- and post-supplementation depression scores, measured using the Hospital Anxiety Depression Scale (HADS) depression subscale (HADS-D), showed a significant decrease within the vitamin D3 group (median HADS-D 4.0 to 3.0, p=0.02), a trend towards a decrease within the placebo group (median HADS-D 3.0 to 2.0, p=0.06), but no significantly different reductions between groups (p=0.78). Furthermore, no reductions in pro- and anti-inflammatory cytokine balances, secreted by stimulated leukocytes and CD8+ T cells, were found in the vitamin D3 compared to the placebo arm. Therefore, we found no evidence for a reduction of depressive symptoms or related biomarkers upon vitamin D3 supplementation in RRMS patients in this exploratory study. Whether vitamin D3 supplementation is of benefit in manifest depression in MS needs to be assessed by additional studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Vitamin D(3 availability and functional activity of peripheral blood phagocytes in experimental type 1 diabetes

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    D. О. Labudzynskyi

    2014-04-01

    Full Text Available The study was devoted to identifying the relation between vitamin D3 availability (assessed by the level of circulatory 25OHD3, content of vitamin D3 25-hydroxylase isozymes CYP27A1 and CYP2R1 in hepatic tissue and functional activity of peripheral blood phagocytes in mice with experimental type 1 diabetes. It has been shown that diabetes is accompanied by the development of vitamin D3-deficiency which is characterized by decreased 25OHD3 content in blood serum and determined by changes in tissue expression of the major isoforms of vitamin D3 25-hydroxylase. The level of hepatic CYP27A1 was revealed to be markedly reduced with a concurrent significant augmentation of CYP2R1. Cholecalciferol administration resulted in normalization of tissue levels of both isoforms of vitamin D3 25-hydroxylase and blood serum 25OHD3 content. Diabetes-associated vitamin D3 deficiency correlated with a decrease in phagocytic activity of granulocytes and monocytes, and their ability to produce antibacterial biooxidants such as reactive oxygen and nitrogen forms. Vitamin D3 efficacy to attenuate these abnormalities of immune function was established, indicating an important immunoregulatory role of cholecalciferol in the phagocytic mechanism of antigens elimination implemented by granulocytes and monocytes.

  18. Stability of Vitamin D3 in fortified yoghurt and yoghurt drink (Doogh).

    Science.gov (United States)

    Jafari, Tina; Askari, Gholamreza; Mirlohi, Maryam; Javanmard, Shaghayegh Haghjooy; Faghihimani, Elham; Fallah, Aziz A

    2016-01-01

    Vitamin D deficiency and insufficiency are recognized as a worldwide problem with serious consequences. Fortification of foods with Vitamin D is a certain approach to improve serum Vitamin D status if the stability of vitamin in the foodstuffs was controlled. The purpose of this study was to examine the stability of Vitamin D3 added to low-fat yogurt and yogurt drink "Doogh" during the products shelf-life. Two kinds of Vitamin D3, water- and oil-dispersible forms, suitable for food fortification, were compared to find out whether they show different stability in the products. The products were packed in opaque or translucent containers. The content of Vitamin D3 was determined by high performance liquid chromatography method. Vitamin D was not affected by the heat treatment (pasteurization) and other processes (homogenization and fermentation). Both water- and oil-dispersible forms were stable during the shelf-life of yogurt samples packed in opaque containers. The Vitamin D3 content of yogurt fortified with water-dispersible form and packed in translucent containers was not stable during the shelf-life and significantly reduced after 1, 2, and 3 weeks of storage compared to the day 0. The Vitamin D3 content of samples fortified with the oil-dispersible form packed in the same container was only stable after 1-week and significantly reduced after 2 and 3 weeks of storage. The Vitamin D3 content of Doogh packed in the opaque containers remained stable during the shelf-life while it was not stable in the samples packed in translucent containers. The results suggested that both forms of Vitamin D are suitable for fortification, and opaque container is a better choice for packaging of the product.

  19. Effects of Submaximal Endurance Training and Vitamin D3 Supplementation on Pain Threshold in Diabetic Rats

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    S. Jalal Taherabadi

    2013-07-01

    Full Text Available Background: According to beneficial effects of endurance training and vitamin D3 in diabetes mellitus, purpose of this study is effects submaximal endurance training and vitamin D3 supplementation on pain threshold in streptozotocin induced diabetic rats.Materials and Methods: Male Wistar rats (250±20 g, N=40 were made diabetic by streptozotocin (60 mg/kg, subcutaneously. 72 h after injection diabetes induction was confirmed by tail vein blood glucose concentration (>300 mg/dl. Then animals were divided to five groups: diabetic control (DC, diabetic trained (DT, diabetic -vitamin D (DD, diabetic trained and vitamin D (DTD, and control (C. Animals were submitted to endurance training by treadmill and vitamin D3 treatment (twice aweek, intrapretonally for 4 weeks. 48 h after at the end of exercise and treatment protocol, we used tail-flick to assess the effects of training and vitamin D3 on thermal pain threshold. We used one way ANOVA statistical analysis to compare differences between groups, significance level of p<0.05 was considered.Results: Diabetic induced hyperalgesia were decreased significantly by vitamin D but not 4 weeks endurance exercise training. Concurrent effects of training and vitamin D on thermal pain threshold were not significantly higher than vitamin D effects alone.Conclusion: It is concluded that vitamin D administration given at the time of diabetes induction may be able to restore thermal hyperalgesia. But effects of endurance exercise training needs to more investigation in diabetic rats.

  20. Role of vitamin D3 in modulation of ΔNp63α expression during UVB induced tumor formation in SKH-1 mice.

    Directory of Open Access Journals (Sweden)

    Natasha T Hill

    Full Text Available ΔNp63α, a proto-oncogene, is up-regulated in non-melanoma skin cancers and directly regulates the expression of both Vitamin D receptor (VDR and phosphatase and tensin homologue deleted on chromosome ten (PTEN. Since ΔNp63α has been shown to inhibit cell invasion via regulation of VDR, we wanted to determine whether dietary Vitamin D3 protected against UVB induced tumor formation in SKH-1 mice, a model for squamous cell carcinoma development. We examined whether there was a correlation between dietary Vitamin D3 and ΔNp63α, VDR or PTEN expression in vivo in SKH-1 mice chronically exposed to UVB radiation and fed chow containing increasing concentrations of dietary Vitamin D3. Although we observed differential effects of the Vitamin D3 diet on ΔNp63α and VDR expression in chronically irradiated normal mouse skin as well as UVB induced tumors, Vitamin D3 had little effect on PTEN expression in vivo. While low-grade papillomas in mice exposed to UV and fed normal chow displayed increased levels of ΔNp63α, expression of both ΔNp63α and VDR was reduced in invasive tumors. Interestingly, in mice fed high Vitamin D3 chow, elevated levels of ΔNp63α were observed in both local and invasive tumors but not in normal skin suggesting that oral supplementation with Vitamin D3 may increase the proliferative potential of skin tumors by increasing ΔNp63α levels.

  1. Exposure to Cigarette Smoke Reduces Vitamin D3 in the Blood Stream and Respiratory Tract

    Science.gov (United States)

    ... blood stream and respiratory tract Share | Exposure to cigarette smoke reduces vitamin D3 in the blood stream and respiratory tract Published Online: April 2, 2014 Cigarette smoking and exposure to secondhand smoke have long ...

  2. Effects of 1,25-dihydroxyvitamin D3 and vitamin D3 on the expression of the vitamin D receptor in human skeletal muscle cells

    Science.gov (United States)

    Vitamin D receptor (VDR) expression and action in non-human skeletal muscle have recently been reported in several studies, yet data on the activity and expression of VDR in human muscle cells are scarce. We conducted a series of studies to examine the (1) effect of 1,25-dihydroxyvitamin D3 (1,25(OH...

  3. Neuroprotective role of vitamin D3 in colchicine-induced Alzheimer's ...

    African Journals Online (AJOL)

    Group II: rats with induced AD by icv colchicine injection of 15 lg/rat bilaterally and receiving no treatment. Group III: rats pre-treated with active form of vitamin D3 42 IU/kg/day subcutaneously (s.c.) for one week followed by induction of AD then post-treated with vitamin D3 in the same dose for 3 weeks. Group IV: rats with ...

  4. Vitamin D3supplementation does not modify cardiovascular risk profile of adults with inadequate vitamin D status.

    Science.gov (United States)

    Seibert, Eric; Lehmann, Ulrike; Riedel, Annett; Ulrich, Christof; Hirche, Frank; Brandsch, Corinna; Dierkes, Jutta; Girndt, Matthias; Stangl, Gabriele I

    2017-03-01

    The Nutrition Societies in Germany, Austria, and Switzerland recommend a daily intake of 20 µg vitamin D 3 for adults when endogenous synthesis is absent. The current study aimed to elucidate whether this vitamin D 3 dose impacts cardiovascular risk markers of adults during the winter months. The study was conducted in Halle (Saale), Germany (51 o northern latitude) as a placebo-controlled, double-blinded, randomised trial (from January to April). A total of 105 apparently healthy subjects (male and female, 20-71 years old) were included. Subjects were randomly allocated to two groups. One group received a daily 20-µg vitamin D 3 dose (n = 54), and the other group received a placebo (n = 51) for 12 weeks. Outcome measures included blood pressure, heart rate, concentrations of renin, aldosterone, serum lipids and vascular calcification markers, and haematologic variables such as pro-inflammatory monocytes. Blood pressure and systemic cardiovascular risk markers remained unchanged by vitamin D 3 supplementation, although serum 25-hydroxyvitamin D 3 increased from 38 ± 14 to 73 ± 16 nmol/L at week 12. The placebo and vitamin D groups did not differ in their final cardiovascular risk profile. Daily supplementation of 20 µg vitamin D 3 during winter is unlikely to change cardiovascular risk profile.

  5. UV-Stressed Daphnia pulex Increase Fitness through Uptake of Vitamin D3.

    Science.gov (United States)

    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.

  6. Comparison of metabolism of vitamins D2 and D3 in children with nutritional rickets.

    Science.gov (United States)

    Thacher, Tom D; Fischer, Philip R; Obadofin, Michael O; Levine, Michael A; Singh, Ravinder J; Pettifor, John M

    2010-09-01

    Children with calcium-deficiency rickets may have increased vitamin D requirements and respond differently to vitamin D(2) and vitamin D(3). Our objective was to compare the metabolism of vitamins D(2) and D(3) in rachitic and control children. We administered an oral single dose of vitamin D(2) or D(3) of 1.25 mg to 49 Nigerian children--28 with active rickets and 21 healthy controls. The primary outcome measure was the incremental change in vitamin D metabolites. Baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations ranged from 7 to 24 and 15 to 34 ng/mL in rachitic and control children, respectively (p children with rickets (29 ± 17 and 25 ± 11 ng/mL, respectively) and in control children (33 ± 13 and 31 ± 16 ng/mL, respectively). 1,25(OH)(2)D rose significantly (p children with rickets. By contrast, control children had no significant increase in 1,25(OH)(2)D (19 ± 28 and 16 ± 38 pg/mL after vitamin D(2) and D(3) administration, respectively). We conclude that in the short term, vitamins D(2) and D(3) similarly increase serum 25(OH)D concentrations in rachitic and healthy children. A marked increase in 1,25(OH)(2)D in response to vitamin D distinguishes children with putative dietary calcium-deficiency rickets from healthy children, consistent with increased vitamin D requirements in children with calcium-deficiency rickets. © 2010 American Society for Bone and Mineral Research.

  7. The effect of vitamin D2 and vitamin D3 on intestinal calcium absorption in Nigerian children with rickets.

    Science.gov (United States)

    Thacher, Tom D; Obadofin, Michael O; O'Brien, Kimberly O; Abrams, Steven A

    2009-09-01

    Children with calcium-deficiency rickets have high 1,25-dihydroxyvitamin D values. The objective of the study was to determine whether vitamin D increased calcium absorption. This was an experimental study. The study was conducted at a teaching hospital. Participants included 17 children with nutritional rickets. The participants were randomized to 1.25 mg oral vitamin D(3) (n = 8) or vitamin D(2) (n = 9). Fractional calcium absorption 3 da after vitamin D administration was measured. Mean baseline 25-hydroxyvitamin D concentrations were 20 ng/ml (range 5-31 ng/ml). The increase in 25-hydroxyvitamin D was equivalent after vitamin D(3) (29 +/- 10 ng/ml) or vitamin D(2) (29 +/- 17 ng/ml). Mean 1,25-dihydroxyvitamin D values increased from 143 +/- 76 pg/ml to 243 +/- 102 pg/ml (P = 0.001), and the increase in 1,25-dihydroxyvitamin D did not differ between vitamin D(2) and vitamin D(3) (107 +/- 110 and 91 +/- 102 ng/ml, respectively). The increment in 1,25-dihydroxyvitamin D was explained almost entirely by the baseline 25-hydroxyvitamin D concentration (r(2) = 0.72; P rickets in Nigerian children is not primarily due to vitamin D-deficient calcium malabsorption.

  8. The Vitamin E Analog Gamma-Tocotrienol (GT3 and Statins Synergistically Up-Regulate Endothelial Thrombomodulin (TM

    Directory of Open Access Journals (Sweden)

    Rupak Pathak

    2016-11-01

    Full Text Available Statins; a class of routinely prescribed cholesterol-lowering drugs; inhibit 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR and strongly induce endothelial thrombomodulin (TM; which is known to have anti-inflammatory; anti-coagulation; anti-oxidant; and radioprotective properties. However; high-dose toxicity limits the clinical use of statins. The vitamin E family member gamma-tocotrienol (GT3 also suppresses HMGCR activity and induces TM expression without causing significant adverse side effects; even at high concentrations. To investigate the synergistic effect of statins and GT3 on TM; a low dose of atorvastatin and GT3 was used to treat human primary endothelial cells. Protein-level TM expression was measured by flow cytometry. TM functional activity was determined by activated protein C (APC generation assay. Expression of Kruppel-like factor 2 (KLF2, one of the key transcription factors of TM, was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR. TM expression increased in a dose-dependent manner after both atorvastatin and GT3 treatment. A combined treatment of a low-dose of atorvastatin and GT3 synergistically up-regulated TM expression and functional activity. Finally; atorvastatin and GT3 synergistically increased KLF2 expression. These findings suggest that combined treatment of statins with GT3 may provide significant health benefits in treating a number of pathophysiological conditions; including inflammatory and cardiovascular diseases.

  9. Vitamin D3 concentration correlates with the severity of multiple sclerosis

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    Saeed Shahbeigi

    2013-01-01

    Full Text Available Background: To investigate the possible association between serum 25(OH vitamin D 3 concentration and the severity of disease in Iranian patients with multiple sclerosis (MS and to compare this concentration with a matched control group. Methods: This was an analytical cross-sectional study performed at Jondishapour Neurology Clinic in Tehran, Iran. Patients with relapsing-remitting MS were categorized by disease severity: mild [0≤ Expanded Disability Status Scale (EDSS ≤3], moderate (3.5≤EDSS≤5.5, and severe (6≤EDSS. Serum concentrations of 25(OH vitamin D 3 , calcium, phosphorus, magnesium, and parathyroid hormone were measured in 98 MS patients and 17 healthy age- and sex-matched controls. Fisher′s exact, Kruskal-Wallis, Mann-Whitney U test, and independent t and Spearman rank correlation tests were used. Results: Serum 25(OH vitamin D 3 concentration was significantly lower in patients with MS, especially in the severe MS subgroup, compared with healthy controls (P=0.047. There was a statistically significant inverse correlation between 25(OH vitamin D 3 concentration and EDSS score (P=0.049, R=-0.168 by Spearman rank correlation test, which was observed in women only (P=0.044, R=-0.199. Conclusions: Our findings not only further disclose the lower level of vitamin D in MS patients in comparison with healthy controls, but also support the association between vitamin D and disease severity in MS.

  10. [Correlation between vitamin D receptor genetic polymorphism and 25-hydroxyvitamin D3 in vitamin D deficiency rickets].

    Science.gov (United States)

    Gong, Yi-Gu; Li, Yu-Ning; Zhang, Wei-Hua; Liu, Li-Jun; Kang, Xi-Guang

    2010-07-01

    To study the correlation between vitamin D receptor genetic polymorphism Fokand vitamin D deficiency rickets in children between 1 to 3 years old, and to explore the significance of hereditary factors in the development of vitamin D deficiency rickets. Sixty-two children with vitamin D deficiency rickets and 60 healthy children as a control group were enrolled. Serum levels of 25-hydroxyvitamin D3 were measured using ELISA. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genetic analysis method was used. A restriction fragment length polymorphism in the vitamin D receptor genetic polymorphism Fok I was tested. The frequencies of the vitamin D receptor genotype and allele were compared between the two groups. Serum 25-hydroxyvitamin D3 levels in the rickets group were significantly lower than those in the control group ( 9.1+/-4.1 ng/mL vs 16.1+/-6.9 ng/mL; Ppolymorphism Fok I was more common in the rickets group than in the control group (53% vs 25%; Ppolymorphism Fok I and vitamin D deficiency rickets. This suggests that vitamin D receptor genetic polymorphism might play an important role in determining susceptibility to development of vitamin D deficiency rickets.

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

    Directory of Open Access Journals (Sweden)

    Etienne Cavalier

    2016-05-01

    Full Text Available 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(OHD3 was performed three, five, seven, 14, 30 and 60 days after supplementation. In fed and fast conditions, the 25(OHD3 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.

  12. The nonskeletal effects of vitamin D3 and the threshold limit associated with the risk of health complications.

    Science.gov (United States)

    Mojto, V; Kolcunova, M; Rausova, Z; Chrenova, J; Dedik, L

    2016-01-01

    To evaluate the threshold limit of vitamin D3 associated with the risk of nonskeletal health complications in humans. Vitamin D3 deficiency is primary caused by a reduced sun exposure, consequent limiting of vitamin D3 production in the skin, and low intake of food with this vitamin. Ninety-two adults (25-95 years old) were admitted to III. Internal clinic or examined in outpatient department of The University hospital in Bratislava. Vitamin D3 levels were determined using electrochemical luminescence immunoassay. The least square method for the results processing was used. Vitamin D3 level 16 ng/ml may be threshold limit for the risk of hypertension, ischaemic heart disease, renal insufficiency and diabetes mellitus. A higher occurrence of the observed diseases was in female and male patients with vitamin D3 levelsvitamin D3vitamin D3≥16 ng/ml (40%) was observed. Concerning the men, the highest increase refers to ischaemic heart disease (67%). The limit value of vitamin D3, 16 ng/ml, confirmed the association between vitamin D3 insufficiency and the presence of hypertension, ischaemic heart disease, renal insufficiency and diabetes mellitus. Its relation to age, sex and other variables was detected (Tab. 1, Fig. 5, Ref. 27).

  13. Protective effects of vitamin D3 against d-galactosamine-induced liver injury in rats.

    Science.gov (United States)

    Colakoglu, Neriman; Kuloglu, Tuncay; Ozan, Enver; Kocaman, Nevin; Dabak, Durrin Ozlem; Parlak, Gozde

    2016-08-01

    In this study, we examined liver damage induced by d-galactosamine (d-GaIN) and the protective effects of vitamin D3 in relation to d-GaIN toxicity. Twenty Wistar albino rats were used in this study. The rats were divided into four groups. Group I rats were used as the control group. Group II rats were given a single intraperitoneal injection of d-GaIN. Group III rats were given a single intraperitoneal injection of d-GaIN, intramuscular vitamin D3 for five days. Group IV rats were given intramuscular vitamin D3 for five days. All of rats were euthanized by cervical decapitation on the fifth day of experiment. Upon completion of the experiment, a midsaggital incision was performed, and the livers of all rats were removed and fixed. The livers were processed to perform TUNEL technique and histochemical staining. During the microscope examination, we observed inflamatory cell infiltration, sinusoidal dilatation, and apoptotic bodies due to d-GaIN exposure. In addition, glycogen content of the group II hepatocytes was significantly decreased. Vitamin D3 treatment provided better structural apperance of the livers in group III. TUNEL positive cells were extremly pervasive in the group II livers. The study found group III TUNEL positive cells at a reduced rate in relation to group II due to vitamin D3 treatment. This findings indicate that d-GaIN causes inflamation in the liver. This inflamation triggers the apoptotic process gradually. Vitamin D3 has potency to decrease the severity of d-GaIN-caused structural liver damage. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Immunoregulation of Inflammatory and Inhibitory Cytokines by Vitamin D3 in Patients with Inflammatory Bowel Diseases.

    Science.gov (United States)

    Alhassan Mohammed, H; Mirshafiey, A; Vahedi, H; Hemmasi, G; Moussavi Nasl Khameneh, A; Parastouei, K; Saboor-Yaraghi, A A

    2017-06-01

    Inflammatory bowel disease (IBD) is a group of idiopathic, chronic and relapsing inflammatory conditions of the gastrointestinal tract, caused by an aberrant and exaggerated immunological response in the gut. Supplementation of vitamin D3 in patients with IBD exerts both direct and indirect regulatory roles on the naïve T cells, thereby maintaining a balance between inflammatory and inhibitory cytokines. The direct actions of vitamin D3 on naïve T cells result in the proliferation of more regulatory T cells and inhibitory cytokines such as IL-4, IL-10 and IL-5. The binding of vitamin D to dendritic cells (DCs) through vitamin D receptors inhibits the action of IL-12 on DCs, resulting in the downregulation of Th1 and Th17. On the other hand, this interaction favours Th2 and Treg upregulation and facilitates the maintenance of immune homoeostasis between inflammatory and inhibitory cytokines which is essentially significant in the management of patients with IBD. The aim of this review was to explore the current and mounting scientific evidence on the roles of vitamin D3 in immunoregulation of inflammatory and inhibitory cytokines in patients with IBDs. An extensive literature search was conducted using keywords such as Vitamin D3*, IBD*, inflammatory cytokines*, inhibitory cytokines*, naïve-T-cells* and antigen presenting cells* through PubMed, SCOPUS and MEDLINE search engines. The results of the accumulated bodies of research that have been conducted demonstrate that vitamin D3 plays a major role not only in the immunoregulation of cytokines involved in the pathogenesis of IBDs but also in many other inflammatory disorders. © 2017 The Foundation for the Scandinavian Journal of Immunology.

  15. Up-regulation of OLR1 expression by TBC1D3 through activation of TNFα/NF-κB pathway promotes the migration of human breast cancer cells.

    Science.gov (United States)

    Wang, Bei; Zhao, Huzi; Zhao, Lei; Zhang, Yongchen; Wan, Qing; Shen, Yong; Bu, Xiaodong; Wan, Meiling; Shen, Chuanlu

    2017-11-01

    Metastatic spread of cancer cells is the most life-threatening aspect of breast cancer and involves multiple steps including cell migration. We recently found that the TBC1D3 oncogene promotes the migration of breast cancer cells, and its interaction with CaM enhances the effects of TBC1D3. However, little is known regarding the mechanism by which TBC1D3 induces the migration of cancer cells. Here, we demonstrated that TBC1D3 stimulated the expression of oxidized low density lipoprotein receptor 1 (OLR1), a stimulator of cell migration, in breast cancer cells at the transcriptional level. Depletion of OLR1 by siRNAs or down-regulation of OLR1 expression using pomalidomide, a TNFα inhibitor, significantly decreased TBC1D3-induced migration of these cells. Notably, TBC1D3 overexpression activated NF-κB, a major effector of TNFα signaling, while inhibition of TNFα signaling suppressed the effects of TBC1D3. Consistent with this, NF-κB inhibition using its specific inhibitor caffeic acid phenethyl ester decreased both TBC1D3-induced OLR1 expression and cell migration, suggesting a critical role for TNFα/NF-κB signaling in TBC1D3-induced migration of breast cancer cells. Mechanistically, TBC1D3 induced activation of this signaling pathway on multiple levels, including by increasing the release of TNFα, elevating the transcription of TNFR1, TRAF1, TRAF5 and TRAF6, and decreasing the degradation of TNFR1. In summary, these studies identify the TBC1D3 oncogene as a novel regulator of TNFα/NF-κB signaling that mediates this oncogene-induced migration of human breast cancer cells by up-regulating OLR1. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Dietary vitamin D3 supplements reduce demyelination in the cuprizone model.

    Directory of Open Access Journals (Sweden)

    Stig Wergeland

    Full Text Available Vitamin D is emerging as a probably important environmental risk factor in multiple sclerosis, affecting both susceptibility and disease progression. It is not known to what extent this effect is due to a modulation of peripheral lymphocyte function, or to intrathecal effects of vitamin D. We investigated the effect of dietary vitamin D3 content on de/remyelination in the cuprizone model, which is a well established toxic model of demyelination, with no associated lymphocyte infiltration. The mice received diets either deficient of (<50 IU/kg, or supplemented with low (500 IU/kg, high (6200 IU/kg or very high (12500 IU/kg amounts of vit D3. Cuprizone (0.2% was added to the diet for six weeks, starting two weeks after onset of the experimental diets. Mouse brain tissue was histopathologically evaluated for myelin and oligodendrocyte loss, microglia/macrophage activation, and lymphocyte infiltration after six weeks of cuprizone exposure, and two weeks after discontinuation of cuprizone exposure. High and very high doses of vitamin D3 significantly reduced the extent of white matter demyelination (p = 0.004 and attenuated microglia activation (p = 0.001. No differences in the density of oligodendrocytes were observed between the diet groups. Two weeks after discontinuation of cuprizone exposure, remyelination was only detectable in the white matter of mice receiving diets deficient of or with low vitamin D3 content. In conclusion, high dietary doses of vitamin D3 reduce the extent of demyelination, and attenuate microglia activation and macrophage infiltration in a toxic model of demyelination, independent of lymphocyte infiltration.

  17. Relation of obesity with serum 25 hydroxy vitamin D3 levels in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Ahmet Cimbek

    2012-01-01

    Full Text Available Background: Hypovitaminosis D is associated with diabetes mellitus (DM. Aim of our study was to determine the relation of obesity with vitamin D levels in type 2 diabetic patients. Materials and Methods: We examined 101 type 2 diabetic patients and made a correlation analysis in all parameters. Then we classified our diabetics according to their body-mass indices and compared their 25 hdroxy vitamin D3 levels. Results: We found negative correlation between 25O HD and body mass index (BMI (P: <0.001, r: -0.23. When we classified our diabetics according to their body mass indices as normal, overweight and obese, and compared their 25 hydroxy vitamin D3 levels, we determined that in every BMI group 25 hydroxy vitamin D levels were not found to be significantly different. Conclusion: These results suggest that at least in a Turkish population with type 2 DM vitamin D levels are low and correlate with BMI, but when vitamin D levels are so low, as obesity worsens vitamin D levels does not lessen.

  18. Vitamin D3 and gargling for the prevention of upper respiratory tract infections: a randomized controlled trial

    OpenAIRE

    Goodall, Emma C; Granados, Andrea C; Luinstra, Kathy; Pullenayegum, Eleanor; Coleman, Brenda L; Loeb, Mark; Smieja, Marek

    2014-01-01

    Background We undertook a 2X2 factorial, randomized controlled trial (RCT) to assess whether vitamin D3 supplementation (10,000 international units per week) versus placebo and gargling versus no gargling could prevent viral, clinical upper respiratory tract infection (URTI) in university students. Methods We randomized 600 students into 4 treatment arms: 1) vitamin D3 and gargling, 2) placebo and gargling, 3) vitamin D3 and no gargling, and 4) placebo and no gargling. Students completed week...

  19. Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Joost Smolders

    2010-12-01

    Full Text Available A poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS. Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS patients. In the present study, we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures.Fifteen RRMS patients were supplemented with 20,000 IU/d vitamin D3 for 12 weeks. Vitamin D and calcium metabolism were carefully monitored, and T cell characteristics were studied by flowcytometry. All patients finished the protocol without side-effects, hypercalcaemia, or hypercalciuria. The median vitamin D status increased from 50 nmol/L (31-175 at week 0 to 380 nmol/L (151-535 at week 12 (P<0.001. During the study, 1 patient experienced an exacerbation of MS and was censored from the T cell analysis. The proportions of (naïve and memory CD4+ Tregs remained unaffected. Although Treg suppressive function improved in several subjects, this effect was not significant in the total cohort (P=0.143. An increased proportion of IL-10+ CD4+ T cells was found after supplementation (P=0.021. Additionally, a decrease of the ratio between IFN-γ+ and IL-4+ CD4+ T cells was observed (P=0.035.Twelve week supplementation of high dose vitamin D3 in RRMS patients was well tolerated and did not induce decompensation of calcium metabolism. The skewing towards an anti-inflammatory cytokine profile supports the evidence on vitamin D as an immune-modulator, and may be used as outcome measure for upcoming randomized placebo-controlled trials.Clinicaltrials.gov NCT00940719.

  20. Skin-Derived Vitamin D-3 Protects against Basal Cell Carcinoma

    NARCIS (Netherlands)

    Bijlsma, Maarten F.; Roelink, Henk

    2017-01-01

    UVR in sunlight causes mutations that drive basal cell carcinomas. However, the incidence of these tumors plateaus with prolonged exposure, but the incidence of other skin cancers increases. Makarova et al. now show that vitamin D-3 produced in the skin by UVR protects against its oncogenic effects

  1. Ultraviolet radiation and Vitamin D3 in amphibian health, behaviour, diet and conservation.

    Science.gov (United States)

    Antwis, R E; Browne, R K

    2009-10-01

    Amphibians are currently suffering a period of mass extinction with approximately 20% of species under severe threat and more than 120 species already extinct. In light of this crisis there is an urgency to establish viable ex situ populations and also find the causes of in situ declines. The role of ultraviolet radiation and Vitamin D(3) in amphibian health directly influences both ex situ and in situ populations. Vitamin D(3) can be photosynthesised endogenously via UV-B radiation (UV-B), or acquired through the diet, and then metabolised to calcitriol the biologically active hormonal form. Although, there is a lack of literature concerning Vitamin D(3) requirements and calcitriol synthesis in amphibians, amphibians are likely to have similar Vitamin D(3) requirements and metabolic processes as other vertebrates due to the phylogenetically conservative nature of calcitriol biosynthesis. Deficiencies in calcitriol in amphibians result in nutritional metabolic bone disease (NMBD) and could compromise reproduction and immunity. However, excess biologically active UV radiation has also proven detrimental across all three amphibian life stages and therefore could impact both in situ and ex situ populations. Here we review the role and necessity of UV-B and calcitriol in amphibians and the potential for negative impacts due to excessive exposure to UV radiation. We also identify priorities for research that could provide critical information for maintaining healthy in ex situ and in situ populations of amphibians.

  2. Neuroprotective role of vitamin D3 in colchicine-induced Alzheimerâ ...

    African Journals Online (AJOL)

    Adham R. Mohamed

    2014-06-14

    Jun 14, 2014 ... Abstract Background: Alzheimer's disease (AD) is a complex neurodegenerative disease charac- terized by progressive decline in memory, language and other cognitive functions. Recent studies provide convincing evidence on the role of vitamin D3 on the nervous system. Aim: To investigate the effect of ...

  3. Role of 1,25-dihydroxyvitamin D (vitamin D3 as immunomodulator in recurrent missed miscarriage

    Directory of Open Access Journals (Sweden)

    Zakia Mahdy Ibrahim

    2013-09-01

    Conclusion: Although statistically insignificant, vitamin D3 oral supplementation has resulted in reducing risk of pregnancy loss up to 15% among women with recurrent miscarriage so it is a matter that is worth more attention and large scale studies with larger sample size may result in more significant results.

  4. Vitamin D3 Supplementation and Upper Respiratory Tract Infections in a Randomized, Controlled Trial

    OpenAIRE

    Rees, Judy R.; Hendricks, Kristy; Barry, Elizabeth L.; Peacock, Janet L.; Mott, Leila A.; Sandler, Robert S.; Bresalier, Robert S.; Goodman, Michael; Bostick, Roberd M.; Baron, John A.

    2013-01-01

    In a trial substudy of 1000 IU vitamin D3 supplementation, 759 participants completed daily health diaries for up to 17 months. Supplementation provided no significant reduction in upper respiratory tract infections, colds, or influenza-like illness during winter or overall.

  5. Vitamin D3 is not effective in the treatment of chronic chilblains

    NARCIS (Netherlands)

    Souwer, I.H.; Lagro-Janssen, A.L.M.

    2009-01-01

    BACKGROUND: Chronic chilblains is a common disease causing major restrictions in daily life, nevertheless little is known about effective treatment. In a literature search, we found thin evidence of three interventions: fluocinolone cream, nifedipine and vitamin D3. OBJECTIVE: We have conducted a

  6. Clinicopathological Studies on Vitamin D(3) Toxicity and Therapeutic Evaluation of Aloe vera in Rats.

    Science.gov (United States)

    Chavhan, Sambhaji G; Brar, R S; Banga, H S; Sandhu, H S; Sodhi, S; Gadhave, P D; Kothule, V R; Kammon, A M

    2011-01-01

    A study was conducted to examine the clinical signs, hematological, biochemical and histopathological changes in vitamin D(3) toxicity at a dose rate 2 mg/kg b.wt. of vitamin D(3) and to assess the protective effect of Aloe vera in vitamin D(3) toxicity. The clinical signs observed were anorexia, progressive weight loss, difficulty in movement and respiration, diarrhea, epistaxis, subnormal body temperature and nervous signs before death. Mortality was observed in treated rats between day 10 and day 19 of treatment. The gross postmortem changes observed were severe emaciation, white chalky deposits on epicardial surface of heart, pin point white deposits on cortical surface of kidneys with pale yellow discoloration and diffused white deposits on serosal surface of stomach and intestine with bloody ingesta in lumen. The hematological changes included non-significant increase in hemoglobin and total leukocyte count and significant increase in relative neutrophil count. The biochemical changes observed were significant increase in plasma concentration of calcium, phosphorus and blood urea nitrogen, whereas a significant decrease in the concentration of albumin and total plasma protein was observed. The histopathological lesions included calcification of various organs, viz., tongue, stomach, intestines, kidney, heart, aorta, larynx, trachea, lungs, spleen, choroid plexus arteries of brain and vas deferens. The Aloe vera juice (2.5% in drinking water) has no protective effect on vitamin D(3) toxicity (2 mg/kg b.wt.).

  7. Activated vitamin D3 and pro-activated vitamin D3 attenuate induction of permanent changes caused by neonatal estrogen exposure in the mouse vagina.

    Science.gov (United States)

    Matsuda, Manabu; Kurosaki, Keiko; Okamura, Naomichi

    2014-01-01

    Exposure of mice to a high dose of estrogens including diethylstilbestrol (DES) during the neonatal period modifies the developmental plan of the genital tract, which leads to various permanent changes in physiology, morphology and gene expression. These changes include development of an abnormal vaginal epithelium lined with hyperplastic mucinous cells accompanied by Tff1 gene expression in mice. Here, the influence of vitamin D on the direct effect of estrogen on the developing mouse vagina was examined. The mid-vagina of neonatal mice was cultured in a serum-free medium containing estradiol-17β (E2) and various concentrations of 1,25-dihydroxyvitamin D3 (1,25(OH)2D) ex vivo and then was transplanted under the renal capsule of ovariectomized host mice for 35 days. Exposure to E2 alone caused the vaginal tissue to develop estrogen-independent epithelial hyperplasia and to express TFF1 mRNA, while addition of a low nanomolar amount of 1,25(OH)2D added at the same time as E2 to the culture medium attenuated the effects of estrogen. Expression of vitamin D receptor was also evident in the neonatal mouse vagina. Interestingly, addition of 25-hydroxyvitamin D3, a pro-activated form of vitamin D, at the micromolar level was found to be potent in disrupting the developmental effects of E2, while cholecalciferol was not at least at the dose examined. Correspondingly, expression of Cyp27B1, a kidney-specific 25-hydroxyvitamin D hydroxylase, was evident in the neonatal mouse vagina when examined by RT-PCR. In addition, simultaneous administration of 1,25(OH)2D successfully attenuated DES-induced ovary-independent hyperplasia in the vagina in neonatal mice in vivo. Thus, manipulation of vitamin D influenced the harmful effects of estrogens on mouse vaginal development.

  8. Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25(OH)D3 metabolism.

    Science.gov (United States)

    Mulligan, Jennifer K; Pasquini, Whitney N; Carroll, William W; Williamson, Tucker; Reaves, Nicholas; Patel, Kunal J; Mappus, Elliott; Schlosser, Rodney J; Atkinson, Carl

    2017-01-01

    Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS). Balb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined. Mice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A. VD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3

  9. Whether vitamin D 3 is effective in reducing proteinuria in type 2 diabetic patients?

    Directory of Open Access Journals (Sweden)

    Nooshin Ahmadi

    2013-01-01

    Full Text Available Background: Nowadays Vitamin D deficiency is a notable medical condition world-wide and also in Iran. Since, vitamin D can have renoprotective effect by inhibiting the renin-angiotensin system; it appears that low vitamin D level can worsen the renal injury in diabetic patients. This study demonstrates the effect of vitamin D 3 therapy on reducing proteinuria in diabetic patients with concomitant diabetic nephropathy and vitamin D deficiency after controlling hypertension and use of angiotensin converting enzyme inhibitors (ACEIs or angiotensin II type receptor blockers (ARBs. Materials and Methods: In this randomized double blinded parallel groups clinical trial, 51 diabetic patients with proven nephropathy and vitamin D deficiency/insufficiency and stable hypertension, dyslipidemia, and hyperglycemic treatment were enrolled. The patients were divided randomly into two groups (treatment and placebo group. Patients received oral vitamin D 3 (pearl 50000 IU or placebo one pearl every week for 12 weeks. Patients were assessed at baseline and 12 weeks after intervention from the point of 25(OH D level, and urine albumin/creatinine ration (UACR. Results: Mean serum 25(OH D concentrations were 14.06 ng/ml and 16.05 ng/ml before treatment. Furthermore, after intervention, its levels were risen to71.23 and 17.63 in drug and placebo groups, respectively. Whereas, UACR as the main variable did not change significantly after intervention in both groups ( P = 0.919. Conclusion: According to our finding, there was not a decrease in proteinuria in diabetic patients who received vitamin D for a period of 3 months.

  10. Dental caries and vitamin D3 in children with growth hormone deficiency: A STROBE compliant study.

    Science.gov (United States)

    Wójcik, Dorota; Krzewska, Aleksandra; Szalewski, Leszek; Pietryka-Michałowska, Elżbieta; Szalewska, Magdalena; Krzewski, Szymon; Pels, Elżbieta; Beń-Skowronek, Iwona

    2018-02-01

    Vitamin D may prevent dental caries. To date, no attempts have been made to examine the correlation between the incidence of caries and the concentrations of vitamin D in children with pituitary growth hormone deficiency.The study observed patients of the Department of Endocrinology and Diabetology of the University Paediatric Hospital of the Medical University of Lublin treated with human recombinant growth hormone for pituitary growth hormone deficiency (GHD). The study was conducted between October 2014 and June 2015. The study group consisted of 121 children and adolescents (6-17 years old), including 56 children from rural areas and 65 children from urban areas. The study group was stratified by area of residence.In our study, the increase in vitamin D3 [25(OH)D] levels reduced the D component by 0.66 per each 10 ng/mL of vitamin D3 concentration. The percentage of children with active caries in rural areas is 91.07% (n = 51), which is significantly higher than the percentage of children with active caries in urban areas (81.54%, n = 53).To date, information regarding the potential possibility of reducing the incidence of dental caries by means of increasing the levels of vitamin D was sidelined by paediatricians and dentists alike. Therefore, this aspect of caries prevention should be highlighted.

  11. Vitamin D status assessed by a validated HPLC method: within and between variation in subjects supplemented with vitamin D3

    DEFF Research Database (Denmark)

    Jakobsen, Jette; Bysted, Anette; Andersen, Rikke

    2009-01-01

    -subject variation of vitamin D status in serum samples from four different dietary intervention studies in which subjects (n=92) were supplemented with different doses of vitamin D3 (5-12 g/day) and for different durations (4-20 months). Results. The HPLC method was applicable for 4.0-200 nmol S-25OHD/L, while...... estimated in each of the four human intervention studies did not differ significantly (p=0.55). Hence, the pooled standard deviation was 15.3 nmol 25OHD3/L. In the studies with 6-8 samplings during 7-20 months of supplementation, the within-subject variation was 3.9-7.2 nmol 25OHD3/L, while vitamin D status...... was in the range 47-120 nmol/L. Conclusions. The validated HPLC method was applied in samples from human intervention studies in which subjects were supplemented with vitamin D3. The estimated standard deviation between and within subjects is useful in the forthcoming decision on setting limits for optimal vitamin...

  12. Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption.

    Science.gov (United States)

    Trinko, Joseph R; Land, Benjamin B; Solecki, Wojciech B; Wickham, Robert J; Tellez, Luis A; Maldonado-Aviles, Jaime; de Araujo, Ivan E; Addy, Nii A; DiLeone, Ralph J

    2016-01-01

    The influence of micronutrients on dopamine systems is not well defined. Using mice, we show a potential role for reduced dietary vitamin D3 (cholecalciferol) in promoting diet-induced obesity (DIO), food intake, and drug consumption while on a high fat diet. To complement these deficiency studies, treatments with exogenous fully active vitamin D3 (calcitriol, 10 µg/kg, i.p.) were performed. Nondeficient mice that were made leptin resistant with a high fat diet displayed reduced food intake and body weight after an acute treatment with exogenous calcitriol. Dopamine neurons in the midbrain and their target neurons in the striatum were found to express vitamin D3 receptor protein. Acute calcitriol treatment led to transcriptional changes of dopamine-related genes in these regions in naive mice, enhanced amphetamine-induced dopamine release in both naive mice and rats, and increased locomotor activity after acute amphetamine treatment (2.5 mg/kg, i.p.). Alternatively, mice that were chronically fed either the reduced D3 high fat or chow diets displayed less activity after acute amphetamine treatment compared with their respective controls. Finally, high fat deficient mice that were trained to orally consume liquid amphetamine (90 mg/L) displayed increased consumption, while nondeficient mice treated with calcitriol showed reduced consumption. Our findings suggest that reduced dietary D3 may be a contributing environmental factor enhancing DIO as well as drug intake while eating a high fat diet. Moreover, these data demonstrate that dopamine circuits are modulated by D3 signaling, and may serve as direct or indirect targets for exogenous calcitriol.

  13. Vitamin D3 Induces Tolerance in Human Dendritic Cells by Activation of Intracellular Metabolic Pathways.

    Science.gov (United States)

    Ferreira, Gabriela Bomfim; Vanherwegen, An-Sofie; Eelen, Guy; Gutiérrez, Ana Carolina Fierro; Van Lommel, Leentje; Marchal, Kathleen; Verlinden, Lieve; Verstuyf, Annemieke; Nogueira, Tatiane; Georgiadou, Maria; Schuit, Frans; Eizirik, Décio L; Gysemans, Conny; Carmeliet, Peter; Overbergh, Lut; Mathieu, Chantal

    2015-02-04

    Metabolic switches in various immune cell subsets enforce phenotype and function. In the present study, we demonstrate that the active form of vitamin D, 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), induces human monocyte-derived tolerogenic dendritic cells (DC) by metabolic reprogramming. Microarray analysis demonstrated that 1,25(OH) 2 D 3 upregulated several genes directly related to glucose metabolism, tricarboxylic acid cycle (TCA), and oxidative phosphorylation (OXPHOS). Although OXPHOS was promoted by 1,25(OH) 2 D 3 , hypoxia did not change the tolerogenic function of 1,25(OH) 2 D 3 -treated DCs. Instead, glucose availability and glycolysis, controlled by the PI3K/Akt/mTOR pathway, dictate the induction and maintenance of the 1,25(OH) 2 D 3 -conditioned tolerogenic DC phenotype and function. This metabolic reprogramming is unique for 1,25(OH) 2 D 3 , because the tolerogenic DC phenotype induced by other immune modulators did not depend on similar metabolic changes. We put forward that these metabolic insights in tolerogenic DC biology can be used to advance DC-based immunotherapies, influencing DC longevity and their resistance to environmental metabolic stress. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Vitamin D3 Induces Tolerance in Human Dendritic Cells by Activation of Intracellular Metabolic Pathways

    Directory of Open Access Journals (Sweden)

    Gabriela Bomfim Ferreira

    2015-02-01

    Full Text Available Metabolic switches in various immune cell subsets enforce phenotype and function. In the present study, we demonstrate that the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH2D3, induces human monocyte-derived tolerogenic dendritic cells (DC by metabolic reprogramming. Microarray analysis demonstrated that 1,25(OH2D3 upregulated several genes directly related to glucose metabolism, tricarboxylic acid cycle (TCA, and oxidative phosphorylation (OXPHOS. Although OXPHOS was promoted by 1,25(OH2D3, hypoxia did not change the tolerogenic function of 1,25(OH2D3-treated DCs. Instead, glucose availability and glycolysis, controlled by the PI3K/Akt/mTOR pathway, dictate the induction and maintenance of the 1,25(OH2D3-conditioned tolerogenic DC phenotype and function. This metabolic reprogramming is unique for 1,25(OH2D3, because the tolerogenic DC phenotype induced by other immune modulators did not depend on similar metabolic changes. We put forward that these metabolic insights in tolerogenic DC biology can be used to advance DC-based immunotherapies, influencing DC longevity and their resistance to environmental metabolic stress.

  15. Effect of dietary vitamin D3 supplementation on meat quality of ...

    African Journals Online (AJOL)

    student

    neck chicken meat. Shear force values of unaged raw or cooked meat were optimized at different levels of 3735 (r2=0.832) and 2512 (r2=0.669) IU of vitamin D3 per kg DM feed, respectively. Shear force values of aged raw or cooked .... 24.77 E. The area receives a mean rainfall of less than 400 mm. Experimental designs ...

  16. Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial.

    Science.gov (United States)

    Rees, Judy R; Hendricks, Kristy; Barry, Elizabeth L; Peacock, Janet L; Mott, Leila A; Sandler, Robert S; Bresalier, Robert S; Goodman, Michael; Bostick, Roberd M; Baron, John A

    2013-11-01

    Randomized controlled trials testing the association between vitamin D status and upper respiratory tract infection (URTI) have given mixed results. During a multicenter, randomized controlled trial of colorectal adenoma chemoprevention, we tested whether 1000 IU/day vitamin D(3) supplementation reduced winter episodes and duration of URTI and its composite syndromes, influenza-like illness (ILI; fever and ≥2 of sore throat, cough, muscle ache, or headache) and colds (no fever, and ≥2 of runny nose, nasal congestion, sneezing, sore throat, cough, swollen or tender neck glands). The 2259 trial participants were aged 45-75, in good health, had a history of colorectal adenoma, and had a serum 25-hydroxyvitamin D level ≥12 ng/mL. They were randomized to vitamin D(3) (1000 IU/day), calcium (1200 mg/day), both, or placebo. Of these, 759 participants completed daily symptom diaries. Secondary data included semiannual surveys of all participants. Among those who completed symptom diaries, supplementation did not significantly reduce winter episodes of URTI (rate ratio [RR], 0.93; 95% confidence interval [CI], .79-1.09) including colds (RR, 0.93; 95% CI, .78-1.10) or ILI (RR, 0.95; 95% CI, .62-1.46), nor did it reduce winter days of illness (RR, 1.13; 95% CI, .90-1.43). There was no significant benefit according to adherence, influenza vaccination, body mass index, or baseline vitamin D status. Semiannual surveys of all participants (N = 2228) identified no benefit of supplementation on ILI (odds ratio [OR], 1.14; 95% CI, .84-1.54) or colds (OR, 1.03; 95% CI, .87-1.23). Supplementation with 1000 IU/day vitamin D(3) did not significantly reduce the incidence or duration of URTI in adults with a baseline serum 25-hydroxyvitamin D level ≥12 ng/mL.

  17. Therapeutic effects of systemic vitamin k2 and vitamin d3 on gingival inflammation and alveolar bone in rats with experimentally induced periodontitis.

    Science.gov (United States)

    Aral, Kübra; Alkan, Banu Arzu; Saraymen, Recep; Yay, Arzu; Şen, Ahmet; Önder, Gözde Özge

    2015-05-01

    The synergistic effects of vitamin D3 and vitamin K2 on bone loss prevention have been reported. This study evaluates the effects of vitamin D3 and vitamin K2 supplementation in conjunction with conventional periodontal therapy (scaling and root planing [SRP]) on gingival interleukin (IL)-1β and IL-10, serum bone alkaline phosphatase (B-ALP) and tartrate-resistant acid phosphatase 5b (TRAP-5b), and calcium and alveolar bone levels in rats with experimentally induced periodontitis. Seventy-two rats were divided into the following groups: 1) healthy; 2) periodontitis; 3) SRP; 4) SRP + vitamin D3; 5) SRP + vitamin K2; and 6) SRP + vitamins K2 and D3. Periodontitis was induced by ligature placement for 7 days, and vitamin K2 (30 mg/kg) and/or vitamin D3 (2 μg/kg) were administered for 10 days in the SRP + vitamin D3, SRP + vitamin K2, and SRP + vitamins K2 and D3 groups by oral gavage. On day 18, the animals were sacrificed, serum B-ALP, TRAP-5b, and calcium levels were measured, gingiva specimens were extracted for IL-1β and IL-10 analysis, and distances between the cemento-enamel junction and alveolar bone crest were evaluated. Alveolar bone levels in the periodontitis group were significantly greater than those in the other five groups. No significant differences were found in gingival IL-1β and IL-10, serum B-ALP and TRAP-5b, and calcium and alveolar bone levels between the groups receiving SRP and vitamins and the group receiving SRP alone. Within the limitations of this study, vitamin D3 and K2 alone or in combination did not affect gingival IL-1β and IL-10, serum B-ALP and TRAP-5b levels, or alveolar bone compared with conventional periodontal therapy alone.

  18. Modulation of quail intestinal and egg shell gland calbindin (Mr 28,000) gene expression by vitamin D3, 1,25-dihydroxyvitamin D3 and egg laying.

    Science.gov (United States)

    Striem, S; Bar, A

    1991-02-01

    The effects of vitamin D3 sources, egg production and egg cycle on the genomic expression of calbindin (Mr 28,000) in the intestine and egg shell gland (ESG) of quail were characterized by Northern blot and solution hybridization, using synthetic oligonucleotide probe. In vitamin D3- or 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3)-fed quail, onset of egg production induced duodenal and ESG calbindin mRNA and calbindin synthesis. Duodenal calbindin mRNA was slightly higher during the period of shell calcification as compared with the period during which shells were not formed (ESG inactivity). ESG calbindin mRNA was markedly higher during the period of shell calcification than of ESG inactivity. Increasing dietary intake of [3H]1 alpha-hydroxyvitamin D3 increased the duodenal, but not ESG, content of 1,25-(OH)2D3 and calbindin. Duodenal calbindin and its mRNA were absent in vitamin D-deficient quail and were not affected by egg laying. ESG calbindin in the vitamin D-deficient quail was not affected by egg laying, but calbindin mRNA increased in the vitamin D-deficient birds during shell calcification. The results suggest that: (a) intestinal calbindin mRNA and calbindin are induced and/or regulated, either directly or indirectly, by 1,25-(OH)2D3; (b) intestinal calbindin and its mRNA are further induced at the onset of egg laying by an additional stimulator besides 1,25-(OH)2D3; (c) 1,25-(OH)2D3 is required for the expression of the latter stimulator; (d) ESG calbindin mRNA and calbindin are induced in egg-laying birds by a stimulator associated with the egg cycle; and (e) the induction of ESG calbindin mRNA does not need vitamin D metabolites, but 1,25-(OH)2D3 is required for the translation of the mRNA.

  19. Interleukin-10 but not transforming growth factor-β1 gene expression is up-regulated by vitamin D treatment in multiple sclerosis patients.

    Science.gov (United States)

    Farsani, Zeinab Shirvani; Behmanesh, Mehrdad; Sahraian, Mohammad Ali

    2015-03-15

    Multiple sclerosis (MS) is an inflammatory and autoimmune disease. Variety of different genetics and environmental factors are involved in MS pathology. The epidemiological studies demonstrated that vitamin D has immune and immunomodulating effects on MS disease. Therefore, this study aims to evaluate the effect of vitamin D treatment on the expression of interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) genes in MS patients. We found that, the expression level of IL-10 gene in treated patients was up-regulated 3.84 times more than before treatment, but the expression level of TGF-β1 was not affected by vitamin D treatment. Also, a significant relationship was observed between vitamin D level and EDSS in MS patients. Our results indicated that the increased level of serum vitamin D and IL-10 gene expression may be associated with the reduction of EDSS scores in MS patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Vitamin D3 in cancer prevention and therapy: the nutritional issue.

    Science.gov (United States)

    Chirumbolo, Salvatore

    2015-09-01

    The action of vitamin D3, in its biological form 1α,25(OH)2vitD3 or calcitriol, may be summarized as a steroid-like hormone able to modulate basic functions of cell encompassing energy balance, stress response, mitochondria biogenesis, intracellular calcium oscillations, and replication/apoptosis mechanisms leading to cell survival. Moreover, calcitriol exerts a potent role as an innate and adaptive immune cytokine as immunity is closely related to self-maintenance through its energetic/metabolic balance and homeostasis of cell turnover. Therefore, vitamin D might be the ancestral form of survival hormones developed with calcified vertebrate bearing skeleton in order to survive far from water. This characteristic may suggest that the role of dietary vitamin D in preventing cancer is simply ancillary to the many factors playing a major role in contrasting impairment in energy balance and cell survival. Most probably, the immune role of calcitriol might be included in the maintenance, mostly by adipose tissue, of an anti-inflammatory, tolerant immune status, depending on the immune tolerance and modulation from the gut. A balance closely modulated by the leptin axis, which when impairments in metabolism occur, such as in insulin resistance or obesity, calcitriol is unable to face at this imbalance, while leptin plays a major role and cancer progression may be promoted. Furthermore, this mechanism promotes epithelial/mesenchymal transition-mediated fibrosis, leading to cancer resistance to immune control and drug action. Interestingly, this pathologic picture is triggered by deficiency in vitamin D from the diet. Therefore, a dietary habit including vitamin D sources, besides flavonoids, may ameliorate lifestyle and health span in most individuals, depending on their genetic background.

  1. Efficacy and tolerability of a high loading dose (25,000 IU weekly) vitamin D3 supplementation in obese children with vitamin D insufficiency/deficiency

    NARCIS (Netherlands)

    Radhakishun, Nalini N E; van Vliet, Mariska; Poland, Dennis C W; Weijer, Olivier; Beijnen, Jos H; Brandjes, Dees P M; Diamant, Michaela; von Rosenstiel, Ines A

    2014-01-01

    BACKGROUND: The recommended dose of vitamin D supplementation of 400 IU/day might be inadequate to treat obese children with vitamin D insufficiency. Therefore, we tested the efficacy and tolerability of a high loading dose vitamin D3 supplementation of 25,000 IU weekly in multiethnic obese

  2. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis123

    Science.gov (United States)

    Lambert, Helen; Hart, Kathryn; Smith, Colin P; Bucca, Giselda; Penson, Simon; Chope, Gemma; Hyppönen, Elina; Berry, Jacqueline; Vieth, Reinhold; Lanham-New, Susan

    2012-01-01

    Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. Objective: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. Design: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. Results: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. Conclusions: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3 could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify. PMID:22552031

  3. Microarray analyses of glucocorticoid and vitamin D3 target genes in differentiating cultured human podocytes.

    Directory of Open Access Journals (Sweden)

    Xiwen Cheng

    Full Text Available Glomerular podocytes are highly differentiated epithelial cells that are key components of the kidney filtration units. Podocyte damage or loss is the hallmark of nephritic diseases characterized by severe proteinuria. Recent studies implicate that hormones including glucocorticoids (ligand for glucocorticoid receptor and vitamin D3 (ligand for vitamin D receptor protect or promote repair of podocytes from injury. In order to elucidate the mechanisms underlying hormone-mediated podocyte-protecting activity from injury, we carried out microarray gene expression studies to identify the target genes and corresponding pathways in response to these hormones during podocyte differentiation. We used immortalized human cultured podocytes (HPCs as a model system and carried out in vitro differentiation assays followed by dexamethasone (Dex or vitamin D3 (VD3 treatment. Upon the induction of differentiation, multiple functional categories including cell cycle, organelle dynamics, mitochondrion, apoptosis and cytoskeleton organization were among the most significantly affected. Interestingly, while Dex and VD3 are capable of protecting podocytes from injury, they only share limited target genes and affected pathways. Compared to VD3 treatment, Dex had a broader and greater impact on gene expression profiles. In-depth analyses of Dex altered genes indicate that Dex crosstalks with a broad spectrum of signaling pathways, of which inflammatory responses, cell migration, angiogenesis, NF-κB and TGFβ pathways are predominantly altered. Together, our study provides new information and identifies several new avenues for future investigation of hormone signaling in podocytes.

  4. Interactive effects of vitamin D3 and strontium on performance, nutrient retention and bone mineral composition in laying hens.

    Science.gov (United States)

    Browning, Linda C; Cowieson, Aaron J

    2015-03-30

    Strontium is currently prescribed for patients with osteoporosis to increase bone density and reduce bone fractures but its relevance in animal nutrition is obscure. In order to investigate the effect of supplemental strontium and vitamin D3 on performance, egg quality and skeletal integrity in poultry a total of 108 laying hens, 99 weeks of age, were fed three levels of strontium (0, 500, 1000 mg kg(-1) ) and two levels of vitamin D3 (2500, 5,000 iu kg(-1)) over a 12-week period. There was an improvement (P strontium at 500 mg kg(-1) and a significant increase in egg weight in those hens fed additional vitamin D3 . Supplemental strontium increased phosphorus, sodium and strontium retention in birds fed 2500 iu D3 kg(-1) but reduced phosphorus, sodium and strontium retention in birds fed 5000 iu D3 kg(-1), resulting in an interaction (P strontium and vitamin D3 . Addition of 5000 iu D3 kg(-1) increased egg weight (P strontium supplementation reduced egg weight (P strontium supplementation reduced (P strontium significantly improved egg production and feed efficiency; however, further investigation needs to be undertaken to refine the optimum level of strontium required to maximize hen performance. The interrelationship between strontium and vitamin D3 requires further exploratory study. © 2014 Society of Chemical Industry.

  5. Effect of vitamin D3 on the cytokine synthesizing activity of cells of gingival fluid

    Directory of Open Access Journals (Sweden)

    Ostrovskaya L.Yu.

    2016-09-01

    Full Text Available Purpose: to study the effect of vitamin D3 on cytokine activity of macrophages and monocytes of gingival fluid. Material and methods. The examination and treatment of 42 patients with chronic generalized periodontitis at the age of 45-50 years were conducted. Gingival fluid was obtained from the periodontal pockets of patients. Material processed statistically. Results. Colecalciferol efficacy in inflammation and processes of destruction of periodontal tissue was twice higher than using traditional therapy. Resistance anti-inflammatory effect of the drug was maintained for 6 months, which had been confirmed by clinical and laboratory investigations. Conclusion. The use of applications of vitamin D in the treatment of periodontitis may achieve compensatory restoration of immune protection of the oral cavity.

  6. Role of Map Kinase in Mediating the Effects of Vitamin D3 Metabolites on Growth Plate Chondrocytes

    National Research Council Canada - National Science Library

    Haris, Ehland

    2003-01-01

    .... The process is required for normal long bone growth and in certain kinds of bone repair. Vitamin D3 plays an important regulatory role in chondrocyte differentiation and maturation and therefore is essential for proper endochondral ossification...

  7. Menaquinone-4 (vitamin K2) up-regulates expression of human intestinal alkaline phosphatase in Caco-2 cells.

    Science.gov (United States)

    Noda, Seiko; Yamada, Asako; Tanabe, Rieko; Nakaoka, Kanae; Hosoi, Takayuki; Goseki-Sone, Masae

    2016-11-01

    Alkaline phosphatase (ALP) hydrolyzes several monophosphate esters into inorganic acid and alcohol. In humans, 4 kinds of ALP isozymes have been identified: tissue-nonspecific ALP, intestinal ALP, placental ALP, and germ cell ALP. Intestinal ALP is expressed at a high concentration in the brush border membrane of intestinal epithelial cells and is known to be affected by several kinds of nutrients, such as lipids, but the physiological function of intestinal ALP has remained elusive. Vitamin K is an essential cofactor for the posttranslational carboxylation of glutamate residues into γ-carboxy glutamate. Menaquinone-4 (MK-4) with 4 isoprene units, vitamin K2, has been shown to induce bone-type ALP activity and osteoblastogenesis in human bone marrow cells. In this study, we investigated the effects of MK-4 on the level of ALP activity and expression of ALP messenger RNA in the human colon carcinoma cell line Caco-2, which is known to differentiate into small intestinal epithelial cells in vitro. After treatment with MK-4, there were significant increases in the ALP activities of Caco-2 cells. Inhibitor and thermal inactivation experiments demonstrated that the increased ALP had properties of intestinal-type ALP. Semiquantitative reverse transcription-polymerase chain reaction analysis revealed that expressions of human intestinal ALP and sucrase-isomaltase, which are intestinal differentiation markers, were highly enhanced in Caco-2 cells by MK-4. This is the first report concerning ALP messenger RNA expression induced by vitamin K2 in Caco-2 cells. Further studies on the physiological functions of human intestinal ALP will provide useful data on the novel effects of vitamin K. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Synthesis and structure-activity relationships of TEI-9647 derivatives as Vitamin D3 antagonists.

    Science.gov (United States)

    Takenouchi, Kazuya; Sogawa, Ryo; Manabe, Kenji; Saitoh, Hiroshi; Gao, Qingzhi; Miura, Daishiro; Ishizuka, Seiichi

    2004-05-01

    The Vitamin D(3) lactone analogues, (23S)- and (23R)-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactone (TEI-9647 and TEI-9648) are antagonists of the 1alpha,25-dihydroxyvitamin D(3) (1alpha,25-(OH)(2)D(3)) nuclear receptor (VDR)-mediated differentiation of human leukemia (HL-60) cells. In order to clarify the structure-Vitamin D antagonistic activity relationship, we paid attention to the unique lactone moiety of TEI-9647 and TEI-9648: alpha-exo-methylene-gamma-lactone structure. We synthesized the exo-methylene-modified analogues (methylene saturated, endo-methylene, methylene-deleted, methyl-substituted, dimethyl-substituted, methylene-replaced with dimethyl and cyclopropane) and oxygen-modified analogues (oxygen atom replaced with nitrogen and carbon atom) by convergent method using palladium-catalyzed coupling reaction or direct modification of VD(3) skeleton. The antagonistic activity in HL-60 cell differentiation evaluating system of these analogues revealed that any exo-methylene-modified analogues and nitrogen analogue did not have the antagonistic activity, on the other hand carbon analogue did show. The results suggest that "alpha-exo-methylene carbonyl" structure of VD(3) side-chain is crucial for antagonistic activity. The structure is integral building block of many natural products which have interesting biological and it is thought that Michael-type addition of alpha-exo-methylene carbonyl structure with protein nucleophiles such as cysteine would play an important role for the activities. According to this theory, Michael-type reaction of TEI-9647 and TEI-9648 with cysteine residue in protein related to VDR/VDRE-mediated genomic actions such as VDR would be essential step of the antagonistic action.

  9. A Sleeping Beauty DNA transposon-based genetic sensor for functional screening of vitamin D3 analogues

    DEFF Research Database (Denmark)

    Staunstrup, Nicklas H; Sharma, Nynne; Bak, Rasmus O

    2011-01-01

    methods that allow a comparative evaluation of drug properties. As a new tool in functional screening of vitamin D3 analogues, we describe a genomically integratable sensor for sensitive drug detection. This system facilitates assessment of the pharmacokinetic and pharmadynamic properties of vitamin D3...... analogues. The tri-cistronic genetic sensor encodes a drug-sensoring protein, a reporter protein expressed from an activated sensor-responsive promoter, and a resistance marker....

  10. Efficacy of micellized vs. fat-soluble vitamin D3 supplementation in healthy school children from Northern India.

    Science.gov (United States)

    Marwaha, Raman K; Yenamandra, Vamsi K; Ganie, Mohammed Asraf; Sethuraman, Gomathy; Sreenivas, Vishnubhatla; Ramakrishnan, Lakshmy; Mathur, Sathish K; Sharma, Vinod K; Mithal, Ambrish

    2016-12-01

    Vitamin D deficiency is a widely recognized public health problem. Efficacy of a recently developed micellized form of vitamin D3 has not been studied. Hence, we undertook this study to compare its efficacy with the conventionally used fat-soluble vitamin D3. In this open-labeled nonrandomized pilot study, we recruited 180 healthy children, aged 13-14 years in two groups and supplemented Group A (60 children) with 60,000 IU of fat-soluble vitamin D3/month with milk and Group B (120 children) with 60,000 IU/month of water miscible vitamin D3 under supervision for 6 months. Serum 25(OD)D, parathyroid hormone (PTH), calcium, phosphate, and alkaline phosphatase (ALP) levels were evaluated before and after supplementation in 156 children (54 in Group A and 102 in Group B) who completed the study. We observed a significantly greater increase in the serum 25(OH)D levels in group B as compared to group A (31.8±9.1 ng/mL vs. 23.7±10.4 ng/mL; p20 ng/mL) as against 83.3% children in group A. Serum PTH and ALP levels declined considerably in both the groups following supplementation. Vitamin D supplementation significantly increased the serum 25(OH)D levels in both groups. Miscible form of vitamin D3 appears to be better in achieving higher levels of serum 25(OH)D than that observed with a similar dose of fat-soluble vitamin D3. Further studies with different dose regimens are required to establish its efficacy over the conventionally used fat-soluble vitamin D3.

  11. Effects of the vitamin D3 analog 1 alpha, 25-dihydroxyvitamin D3-3 beta-bromoacetate on rat osteosarcoma cells: comparison with 1 alpha, 25-dihydroxyvitamin D3.

    Science.gov (United States)

    Van Auken, M; Buckley, D; Ray, R; Holick, M F; Baran, D T

    1996-12-01

    The actions of the hormonal form of vitamin D, 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25-(OH)2 D3], are mediated by both genomic and nongenomic mechanisms. Several vitamin D synthetic analogs have been developed in order to identify and characterize the site(s) of action of 1 alpha, 25-(OH)2D3 in many cell types including osteoblastic cells. We have compared the effects of 1 alpha, 25-(OH)2D3 and a novel 1 alpha, 25-(OH)2D3 bromoester analog (1,25-(OH)2-BE) that covalently binds to vitamin D receptors. Rat osteosarcoma cells that possess (ROS 17/2.8) or lack (ROS 24/1) the classic intracellular vitamin D receptor were studied to investigate genomic and nongenomic actions. In ROS 17/2.8 cells plated at low density, the two vitamin D compounds (1 x 10(-8) M) caused increased cell proliferation, as assessed by DNA synthesis and total cell counts. Northern blot analysis revealed that the mitogenic effect of both agents was accompanied by an increase in steady-state osteocalcin mRNA levels, but neither agent altered alkaline phosphatase mRNA levels in ROS 17/2.8 cells. ROS 17/2.8 cells responded to 1,25-(OH)2-BE but not the natural ligand with a significant increase in osteocalcin secretion after 72, 96, 120, and 144 hr of treatment. Treatment of ROS 17/2.8 cells with the bromoester analog also resulted in a significant decrease in alkaline phosphatase-specific activity. To compare the nongenomic effects of 1 alpha, 25-(OH)2D3 and 1,25-(OH)2-BE intracellular calcium was measured in ROS 24/1 cells loaded with the fluorescent calcium indicator Quin 2. At 2 x 10(-8) M, both 1 alpha,25-(OH)2D3 and 1, 25-(OH)2-BE increased intracellular calcium within 5 min. Both the genomic and nongenomic actions of 1,25-(OH)2-BE are similar to those of 1 alpha,25-(OH)2D3, and since 1,25-(OH)2-BE has more potent effects on osteoblast function than the naturally occurring ligand due to more stable binding, this novel vitamin D analog may be useful in elucidating the structure and function

  12. The Effects of Uric Acid, Serum Vitamin D3, and Their Interaction on Parkinson’s Disease Severity

    Directory of Open Access Journals (Sweden)

    Rokhsareh Meamar

    2015-01-01

    Full Text Available Objectives. In current study, the relationships between serum vitamin D3 levels and serum UA concentrations as well as their interaction with severity of PD were evaluated in a sample of Iranian PD patients. Method. In a cross sectional study at the one of the main referral hospitals in central region of Iran, during September to November 2011, 112 patients were recruited. Severity of PD was evaluated sing H&R stages and UPDRS. Results. The Spearman rank correlation coefficient suggests the negative significant association between serum vitamin D3 and UPDRS in patients aged >62 (r=-0.34, P<0.05. No statistically significant association was observed between the UA levels and severity of PD (represented by H&Y categories in different levels of serum vitamin D3 not only in total sample but also in separate age and sex groups. The linear regression coefficients suggested positive association between UA and serum vitamin D3 with UPDRSIII scores while negative relationship between UA and serum vitamin D3 interaction with UPDRSIII; however it was only statistically significant in age group ≤62 (P<0.05. Conclusion. Our study revealed a negative correlation between interaction of serum vitamin D3 and UA with severity of PD; other studies are required to confirm our findings.

  13. Influence of vitamin D status and vitamin D3 supplementation on genome wide expression of white blood cells: a randomized double-blind clinical trial.

    Science.gov (United States)

    Hossein-nezhad, Arash; Spira, Avrum; Holick, Michael F

    2013-01-01

    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). 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)D20 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. 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 nonskeletal health benefits of vitamin D. ClinicalTrials.gov NCT01696409.

  14. Influence of vitamin D status and vitamin D3 supplementation on genome wide expression of white blood cells: a randomized double-blind clinical trial.

    Directory of Open Access Journals (Sweden)

    Arash Hossein-nezhad

    Full Text Available 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.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(OHD20 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.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 nonskeletal health benefits of vitamin D.ClinicalTrials.gov NCT01696409.

  15. Effects of Vitamin D3 and Paricalcitol on Immature Cardiomyocytes: A Novel Role for Vitamin D Analogs in the Prevention of Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Marco Ruggiero

    2013-06-01

    Full Text Available Cardiovascular diseases are more prevalent in patients with chronic kidney disease than in the general population and they are considered the leading cause of death in patients with end-stage renal disease. The discovery that vitamin D3 plays a considerable role in cardiovascular protection has led, in recent years, to an increase in the administration of therapies based on the use of this molecule; nevertheless, several studies warned that an excess of vitamin D3 may increase the risk of hypercalcemia and vascular calcifications. In this study we evaluated the effects of vitamin D3, and of its selective analog paricalcitol, on immature cardiomyocytes. Results show that vitamin D3 induces cAMP-mediated cell proliferation and significant intracellular calcification. Paricalcitol, however, induces cell differentiation, morphological modifications in cell shape and size, and no intracellular calcification. Furthermore, vitamin D3 and paricalcitol differently affect cardiomyoblasts responses to acetylcholine treatment. In conclusion, our results demonstrate that the effects of vitamin D3 and paricalcitol on cardiomyoblasts are different and, if these in vitro observations could be extrapolated in vivo, they suggest that paricalcitol has the potential for cardiovascular protection without the risk of inducing intracellular calcification.

  16. Metabolism of selective 20-epi-vitamin D3 analogs in rat osteosarcoma UMR-106 cells: Isolation and identification of four novel C-1 fatty acid esters of 1α,25-dihydroxy-16-ene-20-epi-vitamin D3.

    Science.gov (United States)

    Flarakos, Caroline Ceailles; Weiskopf, Andrew; Robinson, Matthew; Wang, Guoshun; Vouros, Paul; Sasso, Gino J; Uskokovic, Milan R; Reddy, G Satyanarayana

    2017-03-01

    Analogs of 1α,25-dihydroxyvitamin D3 (S1) with 20-epi modification (20-epi analogs) possess unique biological properties. We previously reported that 1α,25-dihydroxy-20-epi-vitamin D3 (S2), the basic 20-epi analog is metabolized into less polar metabolites (LPMs) in rat osteosarcoma cells (UMR-106) but not in a perfused rat kidney. Furthermore, we also noted that only selective 20-epi analogs are metabolized into LPMs. For example, 1α,25-dihydroxy-16-ene-20-epi-vitamin D3 (S4), but not 1α,25-dihydroxy-16-ene-23-yne-20-epi-vitamin D3 (S5) is metabolized into LPMs. In spite of these novel findings, the unequivocal identification of LPMs has not been achieved to date. We report here on a thorough investigation of the metabolism of S4 in UMR-106 cells and isolated two major LPMs produced directly from the substrate S4 itself and two minor LPMs produced from 3-epi-S4, a metabolite of S4 produced through C-3 epimerization pathway. Using GC/MS, ESI-MS and (1)H NMR analysis, we identified all the four LPMs of S4 as 25-hydroxy-16-ene-20-epi-vitamin D3-1-stearate and 25-hydroxy-16-ene-20-epi-vitamin D3-1-oleate and their respective C-3 epimers. We report here for the first time the elucidation of a novel pathway of metabolism in UMR-106 cells in which both 1α,25(OH)2-16-ene-20-epi-D3 and 1α,25(OH)2-16-ene-20-epi-3-epi-D3 undergo C-1 esterification into stearic and oleic acid esters. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Optimization of vitamins A and D3loading in re-assembled casein micelles and effect of loading on stability of vitamin D3during storage.

    Science.gov (United States)

    Loewen, Anisa; Chan, Benny; Li-Chan, Eunice C Y

    2018-02-01

    The objectives of this study were to apply response surface methodology to optimize fat-soluble vitamin loading in re-assembled casein micelles, and to evaluate vitamin D stability of dry formulations during ambient or accelerated storage and in fortified fluid skim milk stored under refrigeration. Optimal loading of vitamin A (1.46-1.48mg/100mgcasein) was found at 9.7mM phosphate, 5.5mM citrate and 30.0mM calcium, while optimal loading of vitamin D (1.38-1.46mg/100mg casein) was found at 4.9mM phosphate, 4.0mM citrate and 26.1mM calcium. In general, more vitamin D was retained in vitamin D-re-assembled casein micelles than control powders during storage, while vitamin D loss was not different for vitamin D-re-assembled casein micelles and control fortified milks after 21days of refrigerated storage with light exposure. In conclusion, re-assembled casein micelles with high loading efficiency show promise for improving vitamin D stability during dry storage. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Features of Immune and Metabolic Changes in patients with Combined Endocrine Pathology and Vitamin D3 Deficiency

    Directory of Open Access Journals (Sweden)

    Yu.I. Komisarenko

    2014-06-01

    Methods. The examined patients with DM type 1 and type 2 combined with autoimmune thyroiditis had reduced levels of D3 vitamin. They were divided into two groups of 28 and 30 patients respectively. All patients with autoimmune thyroiditis had hypothyroidism. The levels of Th1-cytokine profile (IFN-γ, TNF-α, IL-2, IL-6, IL-12, Th2-profile (IL-4, IL-5 and IL-10 and IL-17 were determined. The amount of vitamin D3 was assessed by the level of 25(OHD. Results. The patients with combined endocrine disorders — DM and autoimmune thyroiditis (with hypothyroidism secondary to vitamin D3 deficiency had a significant increase in the background concentration of Th1-cytokine profile (IFN-γ, TNF-α, IL-2, IL-6, IL-12 and a reduced cytokine concentrations of Th2-cytokine profile (IL-4, IL-5 as well as IL-10 and IL-17. Conclusions. The presence of two endocrine diseases and florid vitamin D3 deficiency leads to an imbalance in the immune status of patients, supports an autoimmune inflammatory process and contributes to the progression or advanced development of complications. Further research may confirm the need for the use of vitamin D3 for the prevention and treatment of multiple endocrinopathy to correct metabolic and immunological changes.

  19. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study.

    Science.gov (United States)

    Bergman, Peter; Norlin, Anna-Carin; Hansen, Susanne; Rekha, Rokeya Sultana; Agerberth, Birgitta; Björkhem-Bergman, Linda; Ekström, Lena; Lindh, Jonatan D; Andersson, Jan

    2012-01-01

    Low serum levels of 25-hydroxyvitamin D(3) are associated with an increased risk of respiratory tract infections (RTIs). Clinical trials with vitamin D(3) against various infections have been carried out but data are so far not conclusive. Thus, there is a need for additional randomised controlled trials of effects of vitamin D(3) on infections. To investigate if supplementation with vitamin D(3) could reduce infectious symptoms and antibiotic consumption among patients with antibody deficiency or frequent RTIs. A double-blind randomised controlled trial. Karolinska University Hospital, Huddinge. 140 patients with antibody deficiency (selective IgA subclass deficiency, IgG subclass deficiency, common variable immune disorder) and patients with increased susceptibility to RTIs (>4 bacterial RTIs/year) but without immunological diagnosis. Vitamin D(3) (4000 IU) or placebo was given daily for 1 year. The primary endpoint was an infectious score based on five parameters: symptoms from respiratory tract, ears and sinuses, malaise and antibiotic consumption. Secondary endpoints were serum levels of 25-hydroxyvitamin D(3), microbiological findings and levels of antimicrobial peptides (LL-37, HNP1-3) in nasal fluid. The overall infectious score was significantly reduced for patients allocated to the vitamin D group (202 points) compared with the placebo group (249 points; adjusted relative score 0.771, 95% CI 0.604 to 0.985, p=0.04). A single study centre, small sample size and a selected group of patients. The sample size calculation was performed using p=0.02 as the significance level whereas the primary and secondary endpoints were analysed using the conventional p=0.05 as the significance level. Supplementation with vitamin D(3) may reduce disease burden in patients with frequent RTIs.

  20. Quantification of vitamin D3 in feed, food, and pharmaceuticals using high-performance liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Schadt, Heiko S; Gössl, Richard; Seibel, Natalie; Aebischer, Claude-P

    2012-01-01

    A rapid, sensitive, and selective method for the quantification of vitamin D3 (cholecalciferol) in solid and liquid food, feed, and tablets based on HPLC/MS/MS has been developed and validated. The sample preparation procedure consists of a quick and robust alkaline saponification and liquid-liquid extraction, followed by direct injection of the organic extract into the HPLC/MS/MS system for analysis without any further concentration, reconstitution, or prepurification steps. The reduction in sample preparation time was achieved by applying a heart-cutting, two-dimensional chromatography technique prior to positive electrospray ionization selected reaction monitoring MS analysis. Total vitamin D3 (sum of previtamin D3 and vitamin D3) was quantified using an isotopically labeled internal standard. The ionization efficiency of previtamin D3 and vitamin D3 in the positive electrospray ionization mode was found to be very similar. The validation experiments included four feed matrixes, three types of tablets, and 12 food matrixes. The obtained recoveries were between 96.1 and 105.3%, and intermediate precision ranged from 1.32 to 15.6% RSD, with HorRat values between 0.07 and 0.65. For all samples, extraction efficiencies were above 95.8%. Analysis of two certified reference materials (SRM 1849 and BCR-122) gave accuracies of 102.4 and 99.8%, respectively.

  1. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial.

    Science.gov (United States)

    Castro, Mario; King, Tonya S; Kunselman, Susan J; Cabana, Michael D; Denlinger, Loren; Holguin, Fernando; Kazani, Shamsah D; Moore, Wendy C; Moy, James; Sorkness, Christine A; Avila, Pedro; Bacharier, Leonard B; Bleecker, Eugene; Boushey, Homer A; Chmiel, James; Fitzpatrick, Anne M; Gentile, Deborah; Hundal, Mandeep; Israel, Elliot; Kraft, Monica; Krishnan, Jerry A; LaForce, Craig; Lazarus, Stephen C; Lemanske, Robert; Lugogo, Njira; Martin, Richard J; Mauger, David T; Naureckas, Edward; Peters, Stephen P; Phipatanakul, Wanda; Que, Loretta G; Sheshadri, Ajay; Smith, Lewis; Solway, Julian; Sullivan-Vedder, Lisa; Sumino, Kaharu; Wechsler, Michael E; Wenzel, Sally; White, Steven R; Sutherland, E Rand

    2014-05-01

    In asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency. To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels. The VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014. After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized. Oral vitamin D3 (100,000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 µg/d). If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 µg/d for 8 weeks, then to 80 µg/d for 8 weeks if asthma control was maintained. The primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of β-agonists, systemic corticosteroids, and health care). Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks (28% [95% CI, 21%-34%] with vitamin D3 vs 29% [95% CI, 23%-35%] with placebo; adjusted hazard ratio, 0.9 [95% CI, 0.6-1.3]). Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 µg/d [95% CI, 102.2-120.4 µg/d] in the vitamin D3 group vs 126

  2. Vitamin D3-induced hypercalcemia increases carbon tetrachloride-induced hepatotoxicity through elevated oxidative stress in mice

    OpenAIRE

    Yoshioka, Hiroki; Usuda, Haruki; Miura, Nobuhiko; Fukuishi, Nobuyuki; Nonogaki, Tsunemasa; Onosaka, Satomi

    2017-01-01

    The aim of this study was to determine whether calcium potentiates acute carbon tetrachloride (CCl4) -induced toxicity. Elevated calcium levels were induced in mice by pre-treatment with cholecalciferol (vitamin D3; V.D3), a compound that has previously been shown to induce hypercalcemia in human and animal models. As seen previously, mice injected with CCl4 exhibited increased plasma levels of alanine aminotransferase, aspartate aminotransferase, and creatinine; transient body weight loss; a...

  3. A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections.

    Science.gov (United States)

    Li-Ng, M; Aloia, J F; Pollack, S; Cunha, B A; Mikhail, M; Yeh, J; Berbari, N

    2009-10-01

    Vitamin D has been shown to be an important immune system regulator. Vitamin D insufficiency during winter may cause increased susceptibility to upper respiratory tract infections (URIs). To determine whether vitamin D supplementation during the winter season prevents or decreases URI symptoms, 162 adults were randomized to receive 50 microg vitamin D3 (2000 IU) daily or matching placebo for 12 weeks. A bi-weekly questionnaire was used to record the incidence and severity of URI symptoms. There was no difference in the incidence of URIs between the vitamin D and placebo groups (48 URIs vs. 50 URIs, respectively, P=0.57). There was no difference in the duration or severity of URI symptoms between the vitamin D and placebo groups [5.4+/-4.8 days vs. 5.3+/-3.1 days, respectively, P=0.86 (95% CI for the difference in duration -1.8 to 2.1)]. The mean 25-hydroxyvitamin D level at baseline was similar in both groups (64.3+/-25.4 nmol/l in the vitamin D group; 63.0+/-25.8 nmol/l in the placebo group; n.s.). After 12 weeks, 25-hydroxyvitamin D levels increased significantly to 88.5+/-23.2 nmol/l in the vitamin D group, whereas there was no change in vitamin D levels in the placebo group. There was no benefit of vitamin D3 supplementation in decreasing the incidence or severity of symptomatic URIs during winter. Further studies are needed to determine the role of vitamin D in infection.

  4. Use of vitamin d3 and its metabolites in broiler chicken feed on performance, bone parameters and meat quality.

    Science.gov (United States)

    Garcia, Ana Flávia Quiles Marques; Murakami, Alice Eiko; Duarte, Cristiane Regina do Amaral; Rojas, Iván Camilo Ospina; Picoli, Karla Paola; Puzotti, Maíra Mangili

    2013-03-01

    The objective of this experiment was to assess the use of different vitamin D metabolites in the feed of broiler chickens and the effects of the metabolites on performance, bone parameters and meat quality. A total of 952 one-day-old male broiler chicks were distributed in a completely randomised design, with four treatments, seven replicates and 34 birds per experimental unit. The treatments consisted of four different sources of vitamin D included in the diet, D3, 25(OH)D3, 1,25(OH)2D3, and 1α(OH)D3, providing 2000 and 1600 IU of vitamin D in the starter (1 to 21 d) and growth phases (22 to 42 d), respectively. Mean weight, feed:gain and weight gain throughout the rearing period were less in animals fed 1α(OH)D3 when compared with the other treatments (p0.05) for various bone parameters. Meat colour differed among the treatments (p>0.05). All of the metabolites used in the diets, with the exception of 1α(OH)D3, can be used for broiler chickens without problems for performance and bone quality, however, some aspects of meat quality were affected.

  5. Quantification of vitamin D3 and its hydroxylated metabolites in waxy leaf nightshade (Solanum glaucophyllum Desf.), tomato (Solanum lycopersicum L.) and bell pepper (Capsicum annuum L.)

    DEFF Research Database (Denmark)

    Jäpelt, Rie Bak; Silvestro, Daniele; Smedsgaard, Jørn

    2013-01-01

    Changes in vitamin D3 and its metabolites were investigated following UVB- and heat-treatment in the leaves of Solanum glaucophyllum Desf., Solanum lycopersicum L. and Capsicum annuum L. The analytical method used was a sensitive and selective liquid chromatography electrospray ionisation tandem...... mass spectrometry (LC–ESI-MS/MS) method including Diels–Alder derivatisation. Vitamin D3 and 25-hydroxy vitamin D3 were found in the leaves of all plants after UVB-treatment. S. glaucophyllum had the highest content, 200ng vitamin D3/g dry weight and 31ng 25-hydroxy vitamin D3/g dry weight......, and was the only plant that also contained 1,25 dihydroxy vitamin D3 in both free (32ng/g dry weight) and glycosylated form (17ng/g dry weight)....

  6. In vitro vitamin K(2) and 1α,25-dihydroxyvitamin D(3) combination enhances osteoblasts anabolism of diabetic mice.

    Science.gov (United States)

    Poon, Christina C W; Li, Rachel W S; Seto, Sai Wang; Kong, Siu Kai; Ho, Ho Pui; Hoi, Maggie P M; Lee, Simon M Y; Ngai, Sai Ming; Chan, Shun Wan; Leung, George P H; Kwan, Yiu Wa

    2015-11-15

    In this study, we evaluated the anabolic effect and the underlying cellular mechanisms involved of vitamin K2 (10 nM) and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) (10 nM), alone and in combination, on primary osteoblasts harvested from the iliac crests of C57BL/KsJ lean (+/+) and obese/diabetic (db/db) mice. A lower alkaline phosphatase (ALP) activity plus a reduced expression of bone anabolic markers and bone formation transcription factors (osteocalcin, Runx2, Dlx5, ATF4 and OSX) were consistently detected in osteoblasts of db/db mice compared to lean mice. A significantly higher calcium deposits formation in osteoblasts was observed in lean mice when compared to db/db mice. Co-administration of vitamin K2 (10 nM) and 1,25(OH)2D3 (10 nM) caused an enhancement of calcium deposits in osteoblasts in both strains of mice. Vitamins K2 and 1,25(OH)2D3 co-administration time-dependently (7, 14 and 21 days) increased the levels of bone anabolic markers and bone formation transcription factors, with a greater magnitude of increase observed in osteoblasts of db/db mice. Combined vitamins K2 plus 1,25(OH)2D3 treatment significantly enhanced migration and the re-appearance of surface microvilli and ruffles of osteoblasts of db/db mice. Thus, our results illustrate that vitamins K2 plus D3 combination could be a novel therapeutic strategy in treating diabetes-associated osteoporosis. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25(OHD3 metabolism.

    Directory of Open Access Journals (Sweden)

    Jennifer K Mulligan

    Full Text Available Patients with chronic rhinosinusitis with nasal polyps (CRSwNP have been shown to be vitamin D3 (VD3 deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af mouse model of chronic rhinosinusitis (Af-CRS.Balb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined.Mice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A.VD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1

  8. Effect of vitamin D3 on mild to moderate persistent asthmatic patients: A randomized controlled pilot study

    Directory of Open Access Journals (Sweden)

    A D Nageswari

    2014-01-01

    Full Text Available Background: Asthma is a common chronic inflammatory disease of the bronchial airways. Well defined treatment options for asthma are very few. The role of vitamin D 3 on asthma is still baffling. Aim: We have examined the effect of vitamin D 3 supplementation in mild to moderate persistent asthma patients. Materials and Methods: We conducted an open labeled, randomized comparative trial in 48 asthma patients. The study duration was about 90 days. The study had a run-in-period of 2 weeks. At the end of run-in-period, patients were divided into two groups: Usual care group (n = 31 patients received budesonide and formoterol and intervention care group (n = 32 patients received vitamin D 3 supplementation along with their regular medicine. Results: The primary outcome of the study was to measure the improvement in forced expiratory volume in 1 second (FEV 1 . Patients in both groups had a significant improvement in FEV 1 at the end of the study. The mean difference in percentage predicted FEV 1 in usual care and intervention care group was 4.95 and 7.07 respectively. Conclusion: The study concluded that adjunctive therapy of vitamin D 3 is effective in asthma patients. The present study will be an evidence based report; however, future studies are warranted in longer duration of time to substantiate the present findings.

  9. The beneficial effects of vitamin D3 on reducing antibody titers against Epstein-Barr virus in multiple sclerosis patients.

    Science.gov (United States)

    Najafipoor, Adeleh; Roghanian, Rasoul; Zarkesh-Esfahani, Sayyed Hamid; Bouzari, Majid; Etemadifar, Masoud

    2015-03-01

    Recently, the relationship between immunoreactivity to Epstein-Barr virus (EBV) and hypo-vitamin D in multiple sclerosis (MS) patients has been described. The aim of this study was to investigate whether vitamin D3 supplementation in MS patients could influence the immune response against latent EBV infection. Forty MS patients were recruited in this study. Twenty-seven patients were supplemented with 50,000 IU/week of vitamin D3 for 6 months and thirteen enrolled as controls. 25-Hydroxyvitamin D (25OHD) levels and IgG titers against EBNA1 and VCA were determined pre- and post-supplementation. All the patients were seropositive for EBV prior to vitamin D supplementation. In this cohort, 22.5% and 47.5% of the MS patients had deficient and insufficient levels of 25OHD, respectively. Our findings confirm that antibody titers against EBV in MS patients rise after the onset of the disease and indicate that vitamin D3 supplementation could limit augmentation of these titers in MS patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Vitamin D3 and gargling for the prevention of upper respiratory tract infections: a randomized controlled trial.

    Science.gov (United States)

    Goodall, Emma C; Granados, Andrea C; Luinstra, Kathy; Pullenayegum, Eleanor; Coleman, Brenda L; Loeb, Mark; Smieja, Marek

    2014-05-19

    We undertook a 2X2 factorial, randomized controlled trial (RCT) to assess whether vitamin D3 supplementation (10,000 international units per week) versus placebo and gargling versus no gargling could prevent viral, clinical upper respiratory tract infection (URTI) in university students. We randomized 600 students into 4 treatment arms: 1) vitamin D3 and gargling, 2) placebo and gargling, 3) vitamin D3 and no gargling, and 4) placebo and no gargling. Students completed weekly electronic surveys and submitted self-collected mid-turbinate nasal flocked swabs during September and October in 2010 or 2011. Symptomatic students also completed an electronic symptom diary. The primary and secondary outcomes were the occurrence of symptomatic clinical URTI and laboratory confirmed URTI respectively. Of 600 participants, 471 (78.5%) completed all surveys while 43 (7.2%) completed none; 150 (25.0%) reported clinical URTI. Seventy participants (23.3%) randomized to vitamin D3 reported clinical URTI compared to 80 (26.7%) randomized to placebo (RR:0.79, CI95:0.61-1.03, p = 0.09). Eighty-five participants (28.3%) randomized to gargling reported clinical URTI compared to 65 participants (21.7%) randomized to the no gargling arm (RR:1.3, CI95:0.92-1.57, p = 0.19). Laboratory testing identified 70 infections (46.7 per 100 URTIs). Vitamin D3 treatment was associated with a significantly lower risk for laboratory confirmed URTI (RR: 0.54, CI95:0.34-0.84, p = 0.007) and with a significantly lower mean viral load measured as log10 viral copies/mL (mean difference: -0.89, CI95: -1.7, -0.06, p = 0.04). Fewer students assigned to gargling experienced laboratory confirmed URTI, however this was not statistically significant (RR:0.82, CI95:0.53-1.26, p = 0.36). These results suggest that vitamin D3 is a promising intervention for the prevention of URTI. Vitamin D3 significantly reduced the risk of laboratory confirmed URTI and may reduce the risk of clinical infections

  11. UHPLC-PDA Assay for Simultaneous Determination of Vitamin D3 and Menaquinone-7 in Pharmaceutical Solid Dosage Formulation

    Directory of Open Access Journals (Sweden)

    Muhammad Jehangir

    2017-01-01

    Full Text Available A newly developed method based on ultrahigh performance liquid chromatography (UHPLC was optimized for the simultaneous determination of vitamin D3 and menaquinone-7 (MK-7 in tablet formulation in the present study. UHPLC separation of vitamin D3 and MK-7 was performed with ACE Excel 2 C18-PFP column (2 μm, 2.1 × 100 mm at 0.6 mL min−1 flow rate, whereas the mobile phase consisted of methanol/water (19:1, v/v, phase A and isopropyl alcohol (99.9%, phase B containing 0.5% triethylamine. Isocratic separation of both the analytes was performed at 40°C by pumping the mobile phases A and B in the ratio of 50:50 (v/v, pH, 6.0. Both analytes were detected at a wavelength of 265 nm and the injection volume was 1.0 μL. The overall runtime per sample was 4.5 min with retention time of 1.26 and 3.64 min for vitamin D3 and MK-7, respectively. The calibration curve was linear from 5.0 to 100 μg mL−1 for vitamin D3 and MK-7 with a coefficient of determination (R2 ≥ 0.9981, while repeatability and reproducibility (expressed as relative standard deviation were lower than 1.46 and 2.21%, respectively. The proposed HPLC method was demonstrated to be simple and rapid for the determination of vitamin D3 and MK-7 in tablets.

  12. Vitamin D3 levels and NLRP3 expression in murine models of obese asthma: association with asthma outcomes.

    Science.gov (United States)

    Zhang, J-H; Chen, Y-P; Yang, X; Li, C-Q

    2017-11-13

    Vitamin D (25(OH)D3) is an essential nutrient that plays a role in the immune system. Serum 25(OH)D3 is found to be associated with asthma. However, the role of vitamin D in obese asthma remains unclear. Therefore, we investigated the association between vitamin D levels and asthma outcomes in a murine model of obese asthma. We also evaluated NLRP3 inflammasome activity in the pathogenesis of obese asthma. We divided 20 male Balb/c mice (3-4 weeks old) into 4 groups: normal control, asthma, obese, and obese asthma and developed an obese asthma mouse model. Airway hyperreactivity, cytokine concentrations, 25(OH)D3 levels, NLRP3 mRNA and IL-1β mRNA expressions were measured. Lung histology and bronchoalveolar lavage fluid (BALF) cell count were also determined. Obese asthma mice showed a significant increase in airway hyper-responsiveness, airway inflammation, pro-inflammatory cytokine levels and NLRP3 mRNA, IL-1β mRNA expression. Both asthma and obese groups had lower 25(OH)D3 levels. Vitamin D levels in obese asthma were the lowest among all groups. Vitamin D levels correlated negatively with body weight, lung resistance levels at 25 mg/mL of methacholine, total inflammatory cells, and IL-1β and IL-17 concentrations in BALF. These data demonstrated an association between serum vitamin D levels and outcomes of obese asthma, and indicated that NLRP3 inflammasome may play a role in this disorder.

  13. 1α,25(OH)2-3-Epi-Vitamin D3, a Natural Physiological Metabolite of Vitamin D3: Its Synthesis, Biological Activity and Crystal Structure with Its Receptor

    Science.gov (United States)

    Molnár, Ferdinand; Sigüeiro, Rita; Sato, Yoshiteru; Araujo, Clarisse; Schuster, Inge; Antony, Pierre; Peluso, Jean; Muller, Christian; Mouriño, Antonio; Moras, Dino; Rochel, Natacha

    2011-01-01

    Background The 1α,25-dihydroxy-3-epi-vitamin-D3 (1α,25(OH)2-3-epi-D3), a natural metabolite of the seco-steroid vitamin D3, exerts its biological activity through binding to its cognate vitamin D nuclear receptor (VDR), a ligand dependent transcription regulator. In vivo action of 1α,25(OH)2-3-epi-D3 is tissue-specific and exhibits lowest calcemic effect compared to that induced by 1α,25(OH)2D3. To further unveil the structural mechanism and structure-activity relationships of 1α,25(OH)2-3-epi-D3 and its receptor complex, we characterized some of its in vitro biological properties and solved its crystal structure complexed with human VDR ligand-binding domain (LBD). Methodology/Principal Findings In the present study, we report the more effective synthesis with fewer steps that provides higher yield of the 3-epimer of the 1α,25(OH)2D3. We solved the crystal structure of its complex with the human VDR-LBD and found that this natural metabolite displays specific adaptation of the ligand-binding pocket, as the 3-epimer maintains the number of hydrogen bonds by an alternative water-mediated interaction to compensate the abolished interaction with Ser278. In addition, the biological activity of the 1α,25(OH)2-3-epi-D3 in primary human keratinocytes and biochemical properties are comparable to 1α,25(OH)2D3. Conclusions/Significance The physiological role of this pathway as the specific biological action of the 3-epimer remains unclear. However, its high metabolic stability together with its significant biologic activity makes this natural metabolite an interesting ligand for clinical applications. Our new findings contribute to a better understanding at molecular level how natural metabolites of 1α,25(OH)2D3 lead to significant activity in biological systems and we conclude that the C3-epimerization pathway produces an active metabolite with similar biochemical and biological properties to those of the 1α,25(OH)2D3. PMID:21483824

  14. 1α,25(OH2-3-epi-vitamin D3, a natural physiological metabolite of vitamin D3: its synthesis, biological activity and crystal structure with its receptor.

    Directory of Open Access Journals (Sweden)

    Ferdinand Molnár

    Full Text Available BACKGROUND: The 1α,25-dihydroxy-3-epi-vitamin-D3 (1α,25(OH2-3-epi-D3, a natural metabolite of the seco-steroid vitamin D3, exerts its biological activity through binding to its cognate vitamin D nuclear receptor (VDR, a ligand dependent transcription regulator. In vivo action of 1α,25(OH2-3-epi-D3 is tissue-specific and exhibits lowest calcemic effect compared to that induced by 1α,25(OH2D3. To further unveil the structural mechanism and structure-activity relationships of 1α,25(OH2-3-epi-D3 and its receptor complex, we characterized some of its in vitro biological properties and solved its crystal structure complexed with human VDR ligand-binding domain (LBD. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we report the more effective synthesis with fewer steps that provides higher yield of the 3-epimer of the 1α,25(OH2D3. We solved the crystal structure of its complex with the human VDR-LBD and found that this natural metabolite displays specific adaptation of the ligand-binding pocket, as the 3-epimer maintains the number of hydrogen bonds by an alternative water-mediated interaction to compensate the abolished interaction with Ser278. In addition, the biological activity of the 1α,25(OH2-3-epi-D3 in primary human keratinocytes and biochemical properties are comparable to 1α,25(OH2D3. CONCLUSIONS/SIGNIFICANCE: The physiological role of this pathway as the specific biological action of the 3-epimer remains unclear. However, its high metabolic stability together with its significant biologic activity makes this natural metabolite an interesting ligand for clinical applications. Our new findings contribute to a better understanding at molecular level how natural metabolites of 1α,25(OH2D3 lead to significant activity in biological systems and we conclude that the C3-epimerization pathway produces an active metabolite with similar biochemical and biological properties to those of the 1α,25(OH2D3.

  15. Active vitamin D3, 1,25-(OH)2D3, protects against macrovasculopathy in a rat model of type 2 diabetes mellitus.

    Science.gov (United States)

    Ma, R; Deng, X L; Du, G L; Li, C; Xiao, S; Aibibai, Y; Zhu, J

    2016-06-03

    To investigate the protective effect of the active form of vitamin D3, 1,25-(OH)2D3, on macrovasculopathy in rats with type 2 diabetes mellitus (T2DM), 8-week-old male Sprague-Dawley rats were randomly divided into control group, T2DM group, and treatment group. The T2DM model was established after 6 weeks by administering an intraperitoneal injection of streptozotocin (30 mg/kg). 1,25-(OH)2D3 was administered by gavage to rats in the treatment group, and an equal volume of peanut oil was administered to rats in the T2DM group. Fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterols were measured in all rats. The morphology of the thoracic aorta was examined, and the expression of tumor necrosis factor alpha (TNF-α), endothelin (ET), endothelial nitric oxide synthase (eNOS), CD54, and CD106 in the thoracic aorta was determined by immunohistochemistry. The expression of FPG, TG, TC, and LDL-C in rats from the T2DM and treatment groups was significantly elevated compared with rats from the control group (P treatment group, while the expression of CD54 was increased only in the T2DM group (P treatment group were lower than those in the T2DM group (P 25-(OH)2D3 may protect the macrovessels from injury in T2DM rats by inhibiting the expression of TNF-α, CD54, and CD106.

  16. Reduced-fat Gouda-type cheese enriched with vitamin D3effectively prevents vitamin D deficiency during winter months in postmenopausal women in Greece.

    Science.gov (United States)

    Manios, Yannis; Moschonis, George; Mavrogianni, Christina; van den Heuvel, Eghm; Singh-Povel, Cécile M; Kiely, Mairead; Cashman, Kevin D

    2017-10-01

    The primary aim of the present study was to examine the effectiveness of daily consumption of vitamin D 3 -enriched, reduced-fat Gouda-type cheese on 25-hydroxyvitamin D (25(OH)D) concentration in postmenopausal women. Health-related quality of life (HRQL) indices were examined as secondary outcomes. This is a single-blinded (i.e., to study participants), randomized, controlled food-based dietary intervention study. A sample of 79 postmenopausal women (55-75 years old) was randomized either to a control group (CG: n = 39) or an intervention group (IG: n = 40) that consumed, as part of their usual diet, 60 g of either non-enriched or vitamin D 3 enriched Gouda-type cheese, respectively, for eight consecutive weeks (i.e., from January to March 2015). Sixty grams of enriched cheese provided a daily dose of 5.7 μg of vitamin D 3 . There was a differential response of mean (95 % CI) serum 25(OH)D levels in the IG and CG, with the former increasing and the latter decreasing significantly over the eight weeks of the trial [i.e., by 5.1 (3.4, 6.9) nmol/L vs. -4.6 (-6.4, -2.8) nmol/L, P D levels  0.1). Consumption of 60 g of vitamin D 3 -enriched, reduced-fat Gouda-type cheese provided a daily dose of 5.7 μg of additional vitamin D 3 and was effective in increasing mean serum 25(OH)D concentration and in counteracting vitamin D deficiency during winter months in postmenopausal women in Greece.

  17. Effects of the supplementation of vitamin D3 on the growth and vitamin D metabolites in juvenile Siberian sturgeon (Acipenser baerii).

    Science.gov (United States)

    Wang, Liansheng; Xu, Hong; Wang, Yang; Wang, Chang'an; Li, Jinnan; Zhao, Zhigang; Luo, Liang; Du, Xue; Xu, Qiyou

    2017-06-01

    The objective of this study was to evaluate the effects of the supplementation of vitamin D3 on the growth, vitamin D metabolites, and osteocalcin secretion in juvenile Siberian sturgeon (Acipenser baerii). A 90-day growth trial was conducted with juvenile Siberian sturgeon (initial body weight 3.47 ± 0.14 g) fed seven isonitrogenous and isoenergetic practical diets (45% CP and 13% lipid) containing 60 (basal diet), 240, 450, 880, 1670, 3300, or 1.0 × 105 IU/kg feed (D60~D 1.0 × 105) vitamin D3. The results showed that weight gain and specific growth rate increased as the dietary vitamin D3 levels increased from 450 to 3300 IU/kg (P fish fed with D1670 and D3300 diets had higher crude lipid and ash levels than the fish fed the D60 diet (P fish fed D880, D1670, or D3300 diets had higher 25-OH-D3 and 1,25-(OH)2-D3 levels than the fish fed the D60 diet (P fish fed D880, D1670, D3300, or D1.0 × 105 diets had higher osteocalcin levels than the fish fed the D60 diet (P < 0.05). Based on the broken line method analysis of weight gain and osteocalcin, the dietary vitamin D3 requirement of juvenile Siberian sturgeon was estimated to be 1683.30 and 1403.27 IU/kg per diet, respectively.

  18. Effect of vitamin D3 on behavioural and biochemical parameters in diabetes type 1-induced rats.

    Science.gov (United States)

    Calgaroto, Nicéia Spanholi; Thomé, Gustavo Roberto; da Costa, Pauline; Baldissareli, Jucimara; Hussein, Fátima Abdala; Schmatz, Roberta; Rubin, Maribel A; Signor, Cristiane; Ribeiro, Daniela Aymone; Carvalho, Fabiano Barbosa; de Oliveira, Lizielle Souza; Pereira, Luciane Belmonte; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

    2014-08-01

    Diabetes is associated with long-term complications in the brain and reduced cognitive ability. Vitamin D3 (VD3 ) appears to be involved in the amelioration of hyperglycaemia in streptozotocin (STZ)-induced diabetic rats. Our aim was to analyse the potential of VD3 in avoiding brain damage through evaluation of acetylcholinesterase (AChE), Na(+) K(+) -adenosine triphosphatase (ATPase) and delta aminolevulinate dehydratase (δ-ALA-D) activities and thiobarbituric acid reactive substance (TBARS) levels from cerebral cortex, as well as memory in STZ-induced diabetic rats. Animals were divided into eight groups (n = 5): control/saline, control/metformin (Metf), control/VD3 , control/Metf + VD3 , diabetic/saline, diabetic/Metf, diabetic/VD3 and diabetic/Metf + VD3 . Thirty days after treatment, animals were submitted to contextual fear-conditioning and open-field behavioural tests, after which they were sacrificed and the cerebral cortex was dissected. Our results demonstrate a significant memory deficit, an increase in AChE activity and TBARS levels and a decrease in δ-ALA-D and Na(+) K(+) -ATPase activities in diabetic rats when compared with the controls. Treatment of diabetic rats with Metf and VD3 prevented the increase in AChE activity when compared with the diabetic/saline group. In treated diabetic rats, the decrease in Na(+) K(+) -ATPase was reverted when compared with non-treated rats, but the increase in δ-ALA-D activity was not. VD3 prevented diabetes-induced TBARS level and improved memory. Our results show that VD3 can avoid cognitive deficit through prevention of changes in important enzymes such as Na(+) K(+) -ATPase and AChE in cerebral cortex in type 1 diabetic rats. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Dietary vitamin D3 requirement of Chinese yellow-feathered broilers.

    Science.gov (United States)

    Jiang, Shouqun; Jiang, Zongyong; Yang, Kuanmin; Chen, Fang; Zheng, Chuntian; Wang, Li

    2015-09-01

    Three experiments have been conducted to investigate the effects of graded dietary levels of vitamin D3 ( VD3: ) on growth performance, metabolic regulation of calcium (CA), phosphorus (P), and bone development of Chinese yellow-feathered broilers during 3 growth phases: 1 to 21 d, 22 to 42 d, and 43 to 63 d. Dietary Ca and P in the corn-soybean-based diet were adequate. A total of 2,000 1-day-old, 1,600 22-day-old, and 1,600 43-day- old Lingnan yellow male broilers were randomly assigned to 1 of 8 dietary treatments with 5 replicates per treatment (50 birds per replicate for 1 to 21 d, 40 birds for both 22 to 42 d and 43 to 63 d). Dietary levels of VD3 were 100, 200, 300, 400, 500, 600, and 700 IU/kg for treatments 2 to 8 through the addition of VD3 to the basal mash diet which otherwise lacked detectable VD3. Graded doses of VD3 from 0 to 700 IU/kg in the diet produced linear (Pgrowth factor 23, Klotho protein, and parathyroid hormone all decreased with the increasing level of dietary VD3 (Prequirements of Chinese yellow-feathered broilers from 1 to 21 d for optimal tibial ash content were estimated from regression analysis to be 464 IU/kg from 1 to 21 d, 539 IU/kg from 22 to 42 d, and 500 IU/kg from 43 to 63 d. © 2015 Poultry Science Association Inc.

  20. Increase in the dosage amount of vitamin D3 preparations by switching from calcium carbonate to lanthanum carbonate.

    Science.gov (United States)

    Hyodo, Toru; Kawakami, Junko; Mikami, Noriko; Wakai, Haruki; Ishii, Daisuke; Yoshida, Kazunari; Iwamura, Masatsugu; Hida, Miho; Kurata, Yasuhisa

    2014-06-01

    It is widely known that dialysis patients who are administered vitamin D preparations have a better prognosis than patients who are not. In this study, of 22 patients on maintenance dialysis who had been administered calcium (Ca) carbonate in our hospital, we investigated the dosage amount of vitamin D3 preparations after the phosphorus (P) binder was switched from Ca carbonate to the newly developed lanthanum carbonate (LC). After completely switching to LC, the dosage amount of oral vitamin D3 preparation (alfacalcidol equivalent) was significantly increased from 0.094 μg/day to 0.375 μg/day (P = 0.0090). No significant changes were observed in the values of serum corrected Ca, alkaline phosphatase, intact parathyroid hormone and P after switching. The administration of LC enabled complete cessation of the administration of Ca carbonate preparations, and increased the dosage amount of vitamin D3 preparations. Therefore, LC may be a useful P binder to improve patient prognosis. © 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.

  1. Vitamin D3 analog maxacalcitol (OCT) induces hCAP-18/LL-37 production in human oral epithelial cells.

    Science.gov (United States)

    Tada, Hiroyuki; Shimizu, Takamitsu; Nagaoka, Isao; Takada, Haruhiko

    2016-01-01

    Maxacalcitol (22-oxacalcitriol: OCT) is a synthetic vitamin D3 analog with a limited calcemic effect. In this study, we investigated whether OCT increases the production of LL-37/CAP-18, a human cathelicidin antimicrobial peptide, in human gingival/oral epithelial cells. A human gingival epithelial cell line (Ca9-22) and human oral epithelial cell lines (HSC-2, HSC-3, and HSC-4) exhibited the enhanced expression of LL-37 mRNA upon stimulation with OCT as well as active metabolites of vitamins D3 and D2. Among the human epithelial cell lines, Ca9-22 exhibited the strongest response to these vitamin D-related compounds. OCT induced the higher production of CAP-18 (ng/mL order) until 6 days time-dependently in Ca9-22 cells in culture. The periodontal pathogen Porphyromonas gingivalis was killed by treatment with the LL-37 peptide. These findings suggest that OCT induces the production of hCAP-18/LL-37 in a manner similar to that induced by the active metabolite of vitamin D3.

  2. 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

    DEFF Research Database (Denmark)

    Itkonen, Suvi T.; Skaffari, Essi; Saaristo, Pilvi

    2016-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    Piotr Zabul

    2015-06-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  5. Green Tea Polyphenols and Vitamin D3 Protect Bone Microarchitecture in Female Rats with Chronic Inflammation

    Science.gov (United States)

    Our recent study showed that green tea polyphenols (GTP) in conjunction with 1-a-OH¬vit-D3 (vitD3) treatment mitigates lipopolysaccharide (LPS)-induced bone mineral density loss in female rats. This study was undertaken to further explore the mechanism and bone microarchitecture of GTP plus vitD3 in...

  6. Vitamin D receptor in the paraventricular nucleus of the hypothalamus is necessary for beneficial effects of 1,25D[3] on peripheral glucose levels

    Science.gov (United States)

    While a wide range of data correlates low vitamin D levels with type 2 diabetes, few studies examine potential mechanisms by which vitamin D might impact key aspects of metabolism. The active form of 1alpha,25-dihydroxyvitamin D[3] (1,25D[3]; calcitriol) is hydroxylated in the liver and kidney from ...

  7. Winter vitamin D3 supplementation does not increase muscle strength, but modulates the IGF-axis in young children

    DEFF Research Database (Denmark)

    Mortensen, Charlotte; Mølgaard, Christian; Hauger, Hanne

    2018-01-01

    PURPOSE: To explore whether muscle strength, the insulin-like growth factor axis (IGF-axis), height, and body composition were associated with serum 25-hydroxyvitamin D [25(OH)D] and affected by winter vitamin D supplementation in healthy children, and furthermore to explore potential sex...... differences. METHODS: We performed a double-blind, placebo-controlled, dose-response winter trial at 55ºN. A total of 117 children aged 4-8 years were randomly assigned to either placebo, 10, or 20 µg/day of vitamin D3 for 20 weeks. At baseline and endpoint, we measured muscle strength with handgrip...

  8. Immune regulatory effects of high dose vitamin D3 supplementation in a randomized controlled trial in relapsing remitting multiple sclerosis patients receiving IFNβ; the SOLARIUM study.

    Science.gov (United States)

    Muris, Anne-Hilde; Smolders, Joost; Rolf, Linda; Thewissen, Marielle; Hupperts, Raymond; Damoiseaux, Jan

    2016-11-15

    Multiple sclerosis (MS) is characterized by a disturbed immune homeostasis and low serum vitamin D levels are associated with an increased disease activity. While vitamin D has been hypothesized to promote the maintenance of immune homeostasis, vitamin D supplementation could be of benefit to patients with MS. The SOLAR study investigated the effects of high dose vitamin D3 supplementation on clinical outcomes in a randomized controlled trial. Here we present the immune regulatory effects, investigated in the SOLARIUM sub-study. Thirty Dutch relapsing remitting (RR) MS patients treated with IFNβ-1a received high dose vitamin D3 supplementation and 23 patients received placebo during a period of 48weeks. Lymphocytes were phenotypically characterized by flow cytometry and in vitro cytokine secretion was assessed in the presence or absence of 1,25(OH)2D3 using Luminex technology. Changes in immune regulatory parameters were determined within subjects as well as between treatment groups. The proportion of cells in the immune regulatory cell compartment (nTreg, iTreg and Breg) was not altered upon high dose vitamin D3 supplementation. Proportions of T helper subsets were not affected by vitamin D3, except for the proportion of IL4+ Th cells, which decreased in the placebo but not in the vitamin D3 group. T cell cytokine secretion increased, most pronounced for IL5 and latency activated protein of TGFβ, in the placebo group but not in the vitamin D3 group. Lymphocytes remained equally reactive to in vitro 1,25(OH)2D3. In conclusion, high dose vitamin D3 supplementation did not result in a relative increase in lymphocytes with a regulatory phenotype. However, this study supports the hypothesis that vitamin D contributes to the maintenance of immune homeostasis by preventing further disturbance of the T cell compartment early in the disease course of MS. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Low 25(OH) Vitamin D3 Levels Are Associated with Adverse Outcome in Newly-Diagnosed Intensively-Treated Adult Acute Myeloid Leukemia Patients

    Science.gov (United States)

    Lee, Hun Ju; Muindi, Josephia R.; Tan, Wei; Hu, Qiang; Wang, Dan; Liu, Song; Wilding, Gregory E.; Ford, Laurie A.; Sait, Sheila N.J.; Block, Annemarie W.; Adjei, Araba A.; Barcos, Maurice; Griffiths, Elizabeth A; Thompson, James E.; Wang, Eunice S.; Johnson, Candace S; Trump, Donald L.; Wetzler, Meir

    2013-01-01

    Background Several studies suggest that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in acute myeloid leukemia (AML). Methods VD levels were evaluated in 97 consecutive newly diagnosed, intensively-treated AML patients. MicroRNA-expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome. Results Thirty-four (35%) patients had normal 25(OH) vitamin D3 levels (32–100 ng/ml), 34 (35%) insufficient (20–31.9 ng/ml) and 29 (30%) deficient levels (<20 ng/ml). Insufficient/deficient 25(OH) vitamin D3 levels were associated with worse relapse-free survival (RFS) compared to normal vitamin D3 levels. In multivariate analyses, deficient 25(OH) vitamin D3, smoking, European LeukemiaNet Genetic Groups and white blood cell count retained their statistical significance for RFS. A number of microRNAs and SNPs were found to be associated with 25(OH) vitamin D3 level, although none remained significant after multiple test corrections; one 25(OH) vitamin D3 receptor SNP, rs10783219, was associated with lower complete remission rate (p=0.0442), shorter RFS (p=0.0058) and overall survival (p=0.0011). Conclusions It remains to be determined what role microRNA and SNP profiles play in contributing to low 25(OH) vitamin D3 level and/or outcome and whether supplementation will improve AML outcome. PMID:24166051

  10. The ROS-generating and antioxidant systems in the liver of rats treated with prednisolone and vitamin D(3

    Directory of Open Access Journals (Sweden)

    I. O. Shymanskyy

    2014-10-01

    Full Text Available The mechanisms of glucocorticoid-induced disturbances of liver function is currently not fully clarified. Vitamin D3 was previously shown to play an important role in the regulation of impaired oxidative metabolism and detoxification function of the liver associated with the effects of hepatotoxic compounds. The study was undertaken to define the intensity of oxidative metabolism in the rat liver and survival of hepatocytes after prolonged prednisolone administration and to assess whether vitamin D3 is capable to counter glucocorticoid-induced changes. It has been shown that prednisolone (0.5 mg per animal for 30 days leads to 1.6-fold increase in the percentage of necrotic cells among isolated hepatocytes as compared with the control. The glucocorticoid-induced impairment of hepatocellular function was accompanied by enhanced generation of reactive oxygen species (ROS, accumulation of TBA-active products and carbonylated proteins but reduced levels­ of free SH-groups of low molecular weight compounds. It was demonstrated a decrease in the activities of key enzymes of antioxidant system (SOD, catalase, glutathione peroxidase, whereas the activities of pro-oxidant enzymes NAD(PH-quinone oxidoreductase and semicarbazide-sensitive amine oxidase were shown to be increased. Vitamin D3 (and to greater extent in combination with α-tocopherol administration (100 IU on the background of glucocorticoid therapy caused normalizing effects on the level of ROS formation, oxidative modification of biomolecules and activity of antioxidant enzymes resulting in better survival of hepatocytes. These data suggest a potential role of vitamin D3 in the regulation of oxidative metabolism alterations related to hepatotoxic action of glucocorticoids.

  11. 1α,25(OH2 Vitamin D3 Modulates Avian T Lymphocyte Functions without Inducing CTL Unresponsiveness.

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    Nitish Boodhoo

    Full Text Available 1,25-Dihydroxyvitamin D3 (Vitamin D is a naturally synthesized fat soluble vitamin shown to have immunomodulatory, anti-inflammatory and cancer prevention properties in human and murine models. Here, we studied the effects of Vitamin D on the functional abilities of avian T lymphocytes using chicken Interferon (IFN-γ ELISPOT assay, BrdU proliferation assay, Annexin V apoptosis assay and PhosFlow for detecting phosphorylated signalling molecules. The results demonstrate that Vitamin D significantly inhibited the abilities of T lymphocytes to produce IFN-γ and proliferate in vitro (P≤0.05, but retained their ability to undergo degranulation, which is a maker for cytotoxicity of these cells. Similarly, Vitamin D did not inhibit Extracellular signal-Regulated Kinase (ERK 1/2 phosphorylation, a key mediator in T cell signalling, in the stimulated T lymphocytes population, while reduced ERK1/2 phosphorylation levels in the unstimulated cells. Our data provide evidence that Vitamin D has immuno-modulatory properties on chicken T lymphocytes without inducing unresponsiveness and by limiting immuno-pathology can promote protective immunity against infectious diseases of poultry.

  12. Vitamin D3 and androgen receptors in testis and epididymal region of roosters (Gallus domesticus) as affected by epididymal lithiasis.

    Science.gov (United States)

    Oliveira, André G; Dornas, Rubem A P; Kalapothakis, Evanguedes; Hess, Rex A; Mahecha, Germán A B; Oliveira, Cleida A

    2008-12-01

    Epididymal lithiasis is a dysfunction characterized by formation of calcium-rich stones in the epididymal region of roosters, associated with decreased serum testosterone and loss of fertility. The segment most affected by the lithiasis is the efferent ductules, which, in birds, are responsible for reabsorption of calcium and luminal fluid. Therefore, we postulated that epididymal lithiasis could result from local impairment of calcium or fluid homeostasis, culminating in initiation of stone formation. Transepithelial calcium transport depends on vitamin D3 and vitamin D3 receptor (VDR). Based on the fact that VDR are present in efferent ductules, possible changes in the pattern of VDR in roosters affected by the epididymal lithiasis was investigated, to start to gain an understanding of the molecular mechanisms involved in the development of calcium stones. To evaluate the potential impact of androgen reduction, changes in androgen receptor (AR) were also investigated. Both VDR and AR were increased in specific segments of the epididymal region, whereas no alterations were found in the testes of affected animals. The increase in VDR was most likely due to an increase in the number of VDR-positive mononuclear leukocyte infiltrates found in the connective tissue followed by an increase in epithelial receptors. The AR were increased, however, mainly in the epididymal duct epithelium. These results suggest that the vitamin D3 and androgen responsive system may be directly/indirectly involved in the development of the disease.

  13. Dynamics of 1α,25-dihydroxyvitamin D3-dependent chromatin accessibility of early vitamin D receptor target genes.

    Science.gov (United States)

    Seuter, Sabine; Pehkonen, Petri; Heikkinen, Sami; Carlberg, Carsten

    2013-12-01

    The signaling cascade of the transcription factor vitamin D receptor (VDR) is triggered by its specific ligand 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). In this study we demonstrate that in THP-1 human monocytic leukemia cells 87.4% of the 1034 most prominent genome-wide VDR binding sites co-localize with loci of open chromatin. At 165 of them 1α,25(OH)2D3 strongly increases chromatin accessibility and has at further 217 sites weaker effects. Interestingly, VDR binding sites in 1α,25(OH)2D3-responsive chromatin regions are far more often composed of direct repeats with 3 intervening nucleotides (DR3s) than those in ligand insensitive regions. DR3-containing VDR sites are enriched in the neighborhood of genes that are involved in controling cellular growth, while non-DR3 VDR binding is often found close to genes related to immunity. At the example of six early VDR target genes we show that the slope of their 1α,25(OH)2D3-induced transcription correlates with the basal chromatin accessibility of their major VDR binding regions. However, the chromatin loci controlling these genes are indistinguishable in their VDR association kinetics. Taken together, ligand responsive chromatin loci represent dynamically regulated contact points of VDR with the genome, from where it controls early 1α,25(OH)2D3 target genes. © 2013.

  14. LC–MS/MS with atmospheric pressure chemical ionisation to study the effect of UV treatment on the formation of vitamin D3 and sterols in plants

    DEFF Research Database (Denmark)

    Jäpelt, Rie Bak; Silvestro, Daniele; Smedsgaard, Jørn

    2011-01-01

    Some plant species are known to cause calcium intoxification in grazing animals. This has been attributed to the presence of vitamin D3-like activity. However, research into the presence of vitamin D3 in plants has been limited. One reason for this may be limitations in the analytical methods ava...... that vitamin D3 formation in plants is dependent on light exposure.......Some plant species are known to cause calcium intoxification in grazing animals. This has been attributed to the presence of vitamin D3-like activity. However, research into the presence of vitamin D3 in plants has been limited. One reason for this may be limitations in the analytical methods...... available for unambiguous detection and quantification of vitamin D3. This paper presents a new method for determining vitamin D3 and its sterol precursors. The method is based on saponification and extraction followed by solid phase clean-up of the compounds from plant leaves and detection by APCI...

  15. Vitamina D y cáncer: acción antineoplásica de la 1α, 25(OH2 -vitamina D3 Vitamin D and cancer: antineoplastic effects of 1α,25(OH2-vitamin D3

    Directory of Open Access Journals (Sweden)

    Verónica González Pardo

    2012-04-01

    Full Text Available La forma hormonalmente activa de la vitamina D, 1α,25(OH2-vitamina D3 (1α,25(OH2D3, además de desempeñar un rol crucial en el mantenimiento de la homeostasis de calcio en el cuerpo, también regula el crecimiento y la diferenciación de diferentes tipos celulares, incluyendo células cancerosas. Actualmente hay numerosos estudios que investigan los efectos de la hormona en estas células, debido al interés en el uso terapéutico del 1α,25(OH2D3 y de análogos con menor actividad calcémica para el tratamiento o prevención del cáncer. En este trabajo de revisión se describe el sistema endocrino de la vitamina D, su mecanismo de acción, su acción antineoplásica y se provee información sobre los últimos avances en el estudio de nuevos análogos de la hormona con menos actividad calcémica para el tratamiento del cáncer.The hormonal form of vitamin D, 1α,25(OH2-vitamin D3 (1α,25(OH2D3, in addition of playing a central role in the control of calcium homeostasis in the body, regulates the growth and differentiation of different cell types, including cancer cells. At present several epidemiologic and clinical studies investigate the effect of the hormone in these cells due to the interest in the therapeutic use of 1α,25(OH2D3 and analogues with less calcemic activity for prevention or treatment of cancer. This review describes vitamin D endocrine system, its mechanism of action, its antineoplastic activity and provides information about the latest advances in the study of new hormone analogues with less calcemic activity for cancer treatment.

  16. Evaluation of 25 hydroxy vitamin D3 levels in patients with alopecia areata

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    Atiye Oğrum

    2015-03-01

    Full Text Available Background and Design: Current studies link a possible relationship between vitamin D deficiency and many autoimmune diseases. Alopecia areata(AA is a frequent autoimmune dermatological disease. The aim of this study was to investigate the relationship between vitamin D levels and alopecia areata; a frequent autoimmune dermatological disease. Materials and Methods: The 25 hydroxyvitamin D (25 OH D levels of 40 patients with alopecia areata and age, gender and skin phototype matched healthy controls were evaluated. Serum 25 OH D was measured in all subjects, grouped as normal/sufficient (> 30 ng/ml, insufficient (15-30 ng/ml and deficient (0,05. In both groups 97,5% of patients had 25 OH D levels under normal range. Conclusion: Vitamin D levels of patients with AA was similar with the control group This similarity may suggest that a connection between vitamin D and AA does not exist. However, it may also indicate that the relationship between AA and Vitamin D is not via the level but receptor (number and / or structure of vitamin D.

  17. DIFFERENTIATED («SEASON» APPROACH TO THE PROPHYLAXIS OF VITAMIN D3 INSUFFICIENCY IN CHILDREN

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    R.T. Saygitov

    2009-01-01

    Full Text Available Vitamin D is key part of bone tissue metabolism as in children, as in adult. It is considered that the needed quantity of vitamin D is synthesized by skin cells within ultraviolet light. As a result, provision with endogenous vitamin D significantly changes during the year; the maximum can be reached in summer months, lessening in winter. Straight consequence of these changes is insufficient bone mineralization in children. A correction of insufficiency of vitamin D, depending on season, seems to be well-grounded. But still there are some unsolved questions. It’s not clear, when «season» prophylaxis should be started, and how long should it be prolonged. Shall we use fortified food? What criteria can be used for the control of effectiveness of these measures? There is no research on this theme in Russia. Only data from single studies allow supposing that more than a half of Russian children have vitamin D insufficiency.Key words: children, vitamin D, «season» insufficiency, prophylaxis, bone mineral density.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(5:70-79

  18. Simultaneous determination of vitamins A and D3 in dairy products by liquid chromatography-tandem mass spectrometry (LC-MS/MS)

    Science.gov (United States)

    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.

  19. The optimal UV exposure time for vitamin D3 synthesis and erythema estimated by UV observations in Korea

    Science.gov (United States)

    Lee, Y. G.; Koo, J. H.

    2016-12-01

    Solar UV radiation in a wavelength range between 280 to 400 nm has both positive and negative influences on human body. Surface UV radiation is the main natural source of vitamin D, providing the promotion of bone and musculoskeletal health and reducing the risk of a number of cancers and other medical conditions. However, overexposure to surface UV radiation is significantly related with the majority of skin cancer, in addition other negative health effects such as sunburn, skin aging, and some forms of eye cataracts. Therefore, it is important to estimate the optimal UV exposure time, representing a balance between reducing negative health effects and maximizing sufficient vitamin D production. Previous studies calculated erythemal UV and vitamin-D UV from the measured and modelled spectral irradiances, respectively, by weighting CIE Erythema and Vitamin D3 generation functions (Kazantzidis et al., 2009; Fioletov et al., 2010). In particular, McKenzie et al. (2009) suggested the algorithm to estimate vitamin-D production UV from erythemal UV (or UV index) and determined the optimum conditions of UV exposure based on skin type Ⅱ according to the Fitzpatrick (1988). Recently, there are various demands for risks and benefits of surface UV radiation on public health over Korea, thus it is necessary to estimate optimal UV exposure time suitable to skin type of East Asians. This study examined the relationship between erythemally weighted UV (UVEry) and vitamin D weighted UV (UVVitD) from spectral UV measurements during 2006-2010. The temporal variations of the ratio (UVVitD/UVEry) were also analyzed and the ratio as a function of UV index was applied to the broadband UV measured by UV-Biometer at 6 sites in Korea Thus, the optimal UV exposure time for vitamin D3 synthesis and erythema was estimated for diurnal, seasonal, and annual scales over Korea. In summer with high surface UV radiation, short exposure time leaded to sufficient vitamin D and erythema and vice

  20. TRPV6 determines the effect of vitamin D3 on prostate cancer cell growth.

    Directory of Open Access Journals (Sweden)

    V'yacheslav Lehen'kyi

    Full Text Available Despite remarkable advances in the therapy and prevention of prostate cancer it is still the second cause of death from cancer in industrialized countries. Many therapies initially shown to be beneficial for the patients were abandoned due to the high drug resistance and the evolution rate of the tumors. One of the prospective therapeutical agents even used in the first stage clinical trials, 1,25-dihydroxyvitamin D3, was shown to be either unpredictable or inefficient in many cases. We have already shown that TRPV6 calcium channel, which is the direct target of 1,25-dihydroxyvitamin D3 receptor, positively controls prostate cancer proliferation and apoptosis resistance (Lehen'kyi et al., Oncogene, 2007. However, how the known 1,25-dihydroxyvitamin D3 antiproliferative effects may be compatible with the upregulation of pro-oncogenic TRPV6 channel remains a mystery. Here we demonstrate that in low steroid conditions 1,25-dihydroxyvitamin D3 upregulates the expression of TRPV6, enhances the proliferation by increasing the number of cells entering into S-phase. We show that these pro-proliferative effects of 1,25-dihydroxyvitamin D3 are directly mediated via the overexpression of TRPV6 channel which increases calcium uptake into LNCaP cells. The apoptosis resistance of androgen-dependent LNCaP cells conferred by TRPV6 channel is drastically inversed when 1,25-dihydroxyvitamin D3 effects were combined with the successful TRPV6 knockdown. In addition, the use of androgen-deficient DU-145 and androgen-insensitive LNCaP C4-2 cell lines allowed to suggest that the ability of 1,25-dihydroxyvitamin D3 to induce the expression of TRPV6 channel is a crucial determinant of the success or failure of 1,25-dihydroxyvitamin D3-based therapies.

  1. Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Akhirunnesa Mily

    Full Text Available Development of new tuberculosis (TB drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D3 (vitD3 and 4-phenyl butyrate (PBA are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects.To examine if oral adjunctive therapy with 5,000IU vitD3 or 2x500 mg PBA or PBA+vitD3 to standard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients.Adult TB patients (n = 288 were enrolled in a randomized, double-blind, placebo-controlled trial conducted in Bangladesh. Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8. Clinical assessments and sputum smear microscopy were performed weekly up to week 4, fortnightly up to week 12 and at week 24; TB culture was performed at week 0, 4 and 8; concentrations of LL-37 in cells, 25-hydroxyvitamin D3 (25(OHD3 in plasma and ex vivo bactericidal function of monocyte-derived macrophages (MDM were determined at week 0, 4, 8, 12 and additionally at week 24 for plasma 25(OHD3.At week 4, 71% (46/65 of the patients in the PBA+vitD3-group (p = 0.001 and 61.3% (38/62 in the vitD3-group (p = 0.032 were culture negative compared to 42.2% (27/64 in the placebo-group. The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD3-group (p = 0.001 and 2.2 times higher in vitD3-group (p = 0.032 compared to placebo. The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 (p = 0.034. Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo (log rank 11.38, p = 0.01.Adjunct therapy with PBA+vitD3 or vitD3 or PBA to standard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host-directed-therapy in the treatment of TB

  2. Long-Term Vitamin D3 Supplementation Does Not Prevent Colonic Inflammation or Modulate Bone Health in IL-10 Knockout Mice at Young Adulthood

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    Andrea J. Glenn

    2014-09-01

    Full Text Available Inflammatory bowel disease (IBD is an idiopathic disease that can impair bone metabolism. Low vitamin D status has been implicated in its progress. This study used interleukin (IL-10 knockout (KO mice, that develop an intestinal inflammation when housed in a non-sterile environment, to determine if supplementation with vitamin D3 throughout life could mitigate inflammation and attenuate the lower bone mineral content (BMC and density (BMD, and bone strength. Female IL-10 KO mice were randomized 25 or 5000 IU vitamin D3/kg diet throughout pregnancy and lactation. At weaning, offspring received the same or opposite diet as their mother until age three months. Body weight growth was similar among groups within a sex. At three months of age, there were no differences in inflammation and gene expression in the colon of offspring. Male offspring exposed to continuous 25 IU vitamin D3/kg diet had lower (p < 0.001 colonic VDR expression and those exposed only to low vitamin D3 until weaning had higher serum IL-6. There were no differences in femur or vertebral BMC, BMD or bone strength. In summary, long-term exposure to vitamin D3 did not attenuate intestinal inflammation or preserve bone mineral or bone strength. Thus, supplementation with vitamin D3 does not exert anti-inflammatory effects in this mouse model that mimics human inflammatory bowel disease.

  3. Long-term vitamin D3 supplementation does not prevent colonic inflammation or modulate bone health in IL-10 knockout mice at young adulthood.

    Science.gov (United States)

    Glenn, Andrea J; Fielding, Kristina A; Chen, Jianmin; Comelli, Elena M; Ward, Wendy E

    2014-09-22

    Inflammatory bowel disease (IBD) is an idiopathic disease that can impair bone metabolism. Low vitamin D status has been implicated in its progress. This study used interleukin (IL)-10 knockout (KO) mice, that develop an intestinal inflammation when housed in a non-sterile environment, to determine if supplementation with vitamin D3 throughout life could mitigate inflammation and attenuate the lower bone mineral content (BMC) and density (BMD), and bone strength. Female IL-10 KO mice were randomized 25 or 5000 IU vitamin D3/kg diet throughout pregnancy and lactation. At weaning, offspring received the same or opposite diet as their mother until age three months. Body weight growth was similar among groups within a sex. At three months of age, there were no differences in inflammation and gene expression in the colon of offspring. Male offspring exposed to continuous 25 IU vitamin D3/kg diet had lower (p < 0.001) colonic VDR expression and those exposed only to low vitamin D3 until weaning had higher serum IL-6. There were no differences in femur or vertebral BMC, BMD or bone strength. In summary, long-term exposure to vitamin D3 did not attenuate intestinal inflammation or preserve bone mineral or bone strength. Thus, supplementation with vitamin D3 does not exert anti-inflammatory effects in this mouse model that mimics human inflammatory bowel disease.

  4. Model-based meta-analysis for comparing Vitamin D2 and D3 parent-metabolite pharmacokinetics.

    Science.gov (United States)

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

    2017-08-01

    Association of Vitamin D (D3 & D2) and its 25OHD metabolite (25OHD3 & 25OHD2) exposures with various diseases is an active research area. D3 and D2 dose-equivalency and each form's ability to raise 25OHD concentrations are not well-defined. The current work describes a population pharmacokinetic (PK) model for D2 and 25OHD2 and the use of a previously developed D3-25OHD3 PK model [1] for comparing D3 and D2-related exposures. Public-source D2 and 25OHD2 PK data in healthy or osteoporotic populations, including 17 studies representing 278 individuals (15 individual-level and 18 arm-level units), were selected using search criteria in PUBMED. Data included oral, single and multiple D2 doses (400-100,000 IU/d). Nonlinear mixed effects models were developed simultaneously for D2 and 25OHD2 PK (NONMEM v7.2) by considering 1- and 2-compartment models with linear or nonlinear clearance. Unit-level random effects and residual errors were weighted by arm sample size. Model simulations compared 25OHD exposures, following repeated D2 and D3 oral administration across typical dosing and baseline ranges. D2 parent and metabolite were each described by 2-compartment models with numerous parameter estimates shared with the D3-25OHD3 model [1]. Notably, parent D2 was eliminated (converted to 25OHD) through a first-order clearance whereas the previously published D3 model [1] included a saturable non-linear clearance. Similar to 25OHD3 PK model results [1], 25OHD2 was eliminated by a first-order clearance, which was almost twice as fast as the former. Simulations at lower baselines, following lower equivalent doses, indicated that D3 was more effective than D2 at raising 25OHD concentrations. Due to saturation of D3 clearance, however, at higher doses or baselines, the probability of D2 surpassing D3's ability to raise 25OHD concentrations increased substantially. Since 25OHD concentrations generally surpassed 75 nmol/L at these higher baselines by 3 months, there would be no

  5. Pharmacokinetics of alendronate in a combined Alendronate/Vitamin D3 tablet in healthy volunteers using plasma and urine data

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    Chalitpon Na nakorn

    2013-06-01

    Full Text Available Alendronate is indicated for treatment of a variety of bone metabolism disorders. In spite of quite low plasma concentrationsfollowing oral administration, pharmacokinetic study of alendronate based on plasma concentrations had normally been reported for up to 8 h. Due to much longer detectable periods in urine, a number of pharmacokinetic studies have been based upon urinary excretion data. The objective of this study was to determine pharmacokinetics of alendronate following oral administration of combined Alendronate/Vitamin D3 tablet. Blood and urine samples were collected for 10 h after oral administration of a combined Alendronate/Vitamin D3 tablet to healthy volunteers. Alendronate levels in plasma and urine samples were determined by high-performance liquid chromatography (HPLC with fluorescence detection. The analytical method involved co-precipitation of alendronate in plasma or urine samples with calcium and followed by solid-phase extraction (SPE process. Pharmacokinetic parameters were analyzed by the non-compartmental method using WinNonlin. Pharmacokinetics parameters, i.e. Cmax, Tmax, AUC0-10, T1/2, were 56.6±11.8 ng/mL, 1.29±0.39 h, 132.4±46.9 ng·h/mL, and 3.43±2.24 h,respectively. Amount excreted in 10 h urine and maximum excretion rate (Rmax were 578.59±308.9 μg and 143.3±72.8 μg/h, respectively. Although these parameters were different from previously reported values, Rmax obtained at 1.29±0.76 h agreed well with Tmax observed from plasma data. Based upon urinary excretion data, enhanced absorption of alendronate after administration of a combined Alendronate/Vitamin D3 tablet is suggested.

  6. The Correlation of Regulatory T (TReg and Vitamin D3 in Pediatric Nephrotic Syndrome

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    Yunika Nurtyas

    2018-01-01

    Full Text Available Nephrotic syndrome (NS is an autoimmune disease that correlates to the imbalance of regulatory T cells (TReg. This study was aimed to investigate the effect of vitamin D as adjuvant therapy of TReg population in pediatric nephrotic syndrome. This study was designed randomized clinical trial, double blind, with pre- and post-test control groups involving 15 subjects newly diagnosed with NS. Subjects were divided into 2 groups, namely K1 for group treated with prednisone+vitamin D and K2 group for prednisone treatment only. The population of TReg in peripheral blood mononuclear cells (PBMC was analyzed using flowcytometry. Vitamin D serum level was measured through ELISA method. Results showed that there was a significant elevation of TReg (independent t-test, p = 0.010 in K1 group, which was higher than in K2 group. The Pearson test in the K1 group showed that vitamin D level was positively correlated with TReg (p = 0.039, r = 0.779.

  7. The combination of 1α, 25(OH)2 – Vitamin D3, calcium and acetylsalicyclic acid affects azoxymethane-induced aberrant crypt foci and colorectal tumours in rats

    DEFF Research Database (Denmark)

    Mølck, Anne-Marie; Poulsen, Morten; Meyer, Otto A.

    2002-01-01

    Effects of 1alpha,25(OH)(2)-vitamin D(3) and acetylsalicylic acid at various dietary levels of calcium (CaCO(3)) on development of aberrant crypt foci (ACF) and tumours in colon were examined in groups of 16 male F344 rats initiated with azoxymethane and observed for 16 weeks. Calcium was the most...... potent modulator of ACF development. The total number of ACF increased with low calcium and decreased with high calcium. The number of large ACF decreased with any addition of calcium, acetylsalicylic acid and 1alpha,25(OH)(2)-vitamin D(3). High levels of calcium alone or in combination with 1alpha,25(OH......)(2)-vitamin D(3) increased the incidence of tumour-bearing animals. 1alpha,25(OH)(2)-vitamin D(3) and acetylsalicylic acid at 5,000 ppm calcium increased the incidence as well....

  8. A Pathway for the Metabolism of Vitamin D3: Unique Hydroxylated Metabolites Formed during Catalysis with Cytochrome P450scc (CYP11A1)

    National Research Council Canada - National Science Library

    O. Guryev; R. A. Carvalho; S. Usanov; A. Gilep; R. W. Estabrook

    2003-01-01

    Metabolites of vitamin D (D3) (cholecalciferol) are recognized as enzymatically formed chemicals in humans that can influence a wide variety of reactions that regulate a large number of cellular functions...

  9. A randomized clinical trial in vitamin D-deficient adults comparing replenishment with oral vitamin D3 with narrow-band UV type B light: effects on cholesterol and the transcriptional profiles of skin and blood.

    Science.gov (United States)

    Ponda, Manish P; Liang, Yupu; Kim, Jaehwan; Hutt, Richard; Dowd, Kathleen; Gilleaudeau, Patricia; Sullivan-Whalen, Mary M; Rodrick, Tori; Kim, Dong Joo; Barash, Irina; Lowes, Michelle A; Breslow, Jan L

    2017-05-01

    Background: Vitamin D deficiency, defined as a serum 25-hydroxyvitamin D [25(OH)D] concentration vitamin D supplementation does not lower LDL-cholesterol concentrations or raise HDL-cholesterol concentrations. This uncoupling between association and causation may result from a failure of oral vitamin D to mimic the effect of dermally synthesized vitamin D in response to ultraviolet type B (UVB) light.Objective: We tested the hypothesis that, in vitamin D-deficient adults, the replenishment of vitamin D with UVB exposure would lower LDL-cholesterol concentrations compared with the effect of oral vitamin D3 supplementation.Design: We performed a randomized clinical trial in vitamin D-deficient adults and compared vitamin D replenishment between subjects who received oral vitamin D3 (n = 60) and those who received narrow-band UVB exposure (n = 58) ≤6 mo.Results: There was no difference in the change from baseline LDL-cholesterol concentrations between oral vitamin D3 and UVB groups (difference in median of oral vitamin D3 minus that of UVB: 1.5 mg/dL; 95% CI: -5.0, 7.0 mg/dL). There were also no differences within groups or between groups for changes in total or HDL cholesterol or triglycerides. Transcriptional profiling of skin and blood, however, revealed significant upregulation of immune pathway signaling with oral vitamin D3 but significant downregulation with UVB.Conclusions: Correcting vitamin D deficiency with either oral vitamin D3 or UVB does not improve the lipid profile. Beyond cholesterol, these 2 modalities of raising 25(OH)D have disparate effects on gene transcription. This trial was registered at clinicaltrials.gov as NCT01688102. © 2017 American Society for Nutrition.

  10. Relationships of low serum vitamin D3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity

    Directory of Open Access Journals (Sweden)

    McGill Anne-Thea

    2008-01-01

    Full Text Available Abstract Low serum 25 hydroxyvitamin D3 (vitamin D3 is known to perturb cellular function in many tissues, including the endocrine pancreas, which are involved in obesity and type II diabetes mellitus (TIIDM. Vitamin D3 insufficiency has been linked to obesity, whether obesity is assessed by body mass index (BMI or waist circumference (waist. Central obesity, using waist as the surrogate, is associated with the metabolic syndrome (MetSyn, insulin resistance, TIIDM and atherosclerotic cardiovascular disease (CVD. We tested how vitamin D3 was related to measures of fat mass, MetSyn markers, haemoglobin A1c (HbA1c and MetSyn in a cross-sectional sample of 250 overweight and obese adults of different ethnicities. There were modest inverse associations of vitamin D3 with body weight (weight (r = -0.21, p = 0.0009, BMI (r = -0.18, p = 0.005, waist (r = -0.14, p = 0.03, [but not body fat % (r = -0.08, p = 0.24], and HbA1c (r = -0.16, p = 0.01. Multivariable regression carried out separately for BMI and waist showed a decrease of 0.74 nmol/L (p = 0.002 in vitamin D3 per 1 kg/m2 increase in BMI and a decrease of 0.29 nmol/L (p = 0.01 per 1 cm increase in waist, with each explaining approximately 3% of the variation in vitamin D3 over and above gender, age, ethnicity and season. The similar relationships of BMI and waist with vitamin D3 may have been due to associations between BMI and waist, or coincidental, where different mechanisms relating hypovitaminosis D3 to obesity occur concurrently. Previously reviewed mechanisms include that 1 low vitamin D3, may impair insulin action, glucose metabolism and various other metabolic processes in adipose and lean tissue 2 fat soluble-vitamin D3 is sequestered in the large adipose compartment, and low in serum, 3 obese people may be sensitive about their body shape, minimising their skin exposure to view and sunlight (not tested. We showed evidence for the first theory but no evidence to support the second. In

  11. Vitamin D3 Adjuvant Treatment Stimulate Interleukin-10 Expression in Children with Nephrotic Syndrome Without Affecting to Clinical Outcome and Glucocorticoid Receptor Expression

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    Husnul Asariati

    2014-11-01

    Full Text Available Idiopathic nephrotic syndrome (INS is the most glomerular disease that occurred in childhood with high rate morbidity. Glucocorticoid is drug of choice for INS and responsiveness to this drug determined prognosis.Glucocorticoid upregulate transcription of anti-inflammatory cytokines such as IL-4 and IL-10. IL-10 is an anti-inflammatory cytokine and has multiple role in immune response include modulate Th1/Th2 response. Vitamin D3 interact with glucocorticoid signaling. Administered active form of vitamin D3 increase dexamethasone-induced IL-10 expression by regulatory T cells in steroid resistant asthmatic patient. Here we showed increase of CD4+ IL10+ expression after treatment both prednisone only and combination prednison with vitamin D3. Both in new-onset NS or rare relaps NS, combination treatment prednisone + vitamin D3 increase CD4+ IL10+ expression significantly compared to prednisone-only treated group (p= 0.003, which first group (new-onset nephrotic syndrome + prednisone and vitamin D3 treatment showed the most CD4+ IL10+ expression enhancement (9.53±3.89. However this study failed to show a correlation between CD4+ IL-10+ expression after prednisone and vitamin D3 treatment with clinical outcome (linear regression test, p= 0,125. This study also showed that there was a no correlation between CD4+ IL-10+ expression and CD3+ GR expression after prednison + vitamin D3 treatment (p= 0.088. CD4+ IL-10+ expression in new-onset and rarely relapsing nephrotic syndrome patients higher in prednisone + vitamin D3 treated group than prednisone-only treated group. There is no correlation between CD4+ IL-10+ expression and CD3+ GR expression nor CD4+ IL-10+ expression and clinical outcome.

  12. 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

    Science.gov (United States)

    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...

  13. Effect of vitamin D3 on leukocyte infiltration into the brain of C57/BL6 mice with experimental autoimmune encephalomyelitis

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    ghasem Mosayebi

    2006-11-01

    Material and methods: Male C57BL/6 mice were divided into two therapeutic groups (n=8 per group with age and weight-matched as follow: Vitamin D3-treated EAE mice (5μg/kg/every two days of vitamin D3 given i.p. from day -3 until day +19 after disease induction. Non-treated EAE mice (EAE control received vehicle alone with same schedule. In addition, 5 age and weight-matched male C57BL/6 mice served as normal (non-EAE controls. Results: Vitamin D3-treated mice had significantly less clinical score of EAE (3.2±0.8 than non-treated mice (5.3±0.44, (p<0.001. Also, there was a significant difference between vitamin D3-trated and non treated mice (p<0.01 in relation to the number of the infiltrating cells in the brain. Conclusion: These results indicate that vitamin D3 treatment reduces infiltration of leukocytes into the brain of EAE mice, and ameliorate the disease. Thus, vitamin D3 treatment may be of therapeutic value against inflammatory disease processes associated with infiltration of activated mononuclear cells into the tissue.

  14. Effect of high-dose vitamin D3 supplementation on antibody responses against Epstein-Barr virus in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Røsjø, Egil; Lossius, Andreas; Abdelmagid, Nada; Lindstrøm, Jonas C; Kampman, Margitta T; Jørgensen, Lone; Sundström, Peter; Olsson, Tomas; Steffensen, Linn H; Torkildsen, Øivind; Holmøy, Trygve

    2017-03-01

    Elevated antibody levels against Epstein-Barr virus (EBV) and a poor vitamin D status are environmental factors that may interact in relapsing-remitting multiple sclerosis (RRMS) aetiology. To examine effects of high-dose oral vitamin D3 supplementation on antibody levels against EBV nuclear antigen 1 (EBNA1) in RRMS. Serum 25-hydroxyvitamin D3 (25(OH)D) and immunoglobulin G antibody levels against EBNA1 (whole protein and amino acid 385-420 fragment), EBV viral capsid antigen (VCA), cytomegalovirus (CMV) and varicella zoster virus (VZV) were measured in 68 RRMS patients enrolled in a 96-week randomised double-blinded placebo-controlled clinical trial of oral vitamin D3 supplementation (20,000 IU/week) (NCT00785473). The mean 25(OH)D level more than doubled in the vitamin D group and was significantly higher than in the placebo group at study conclusion (123.2 versus 61.8 nmol/L, p vitamin D group from baseline to week 48 ( p = 0.038 and p = 0.004, respectively), but not from baseline to week 96. Vitamin D3 supplementation did not affect antibodies against VCA, CMV or VZV. The results indicate that high-dose oral vitamin D3 supplementation can affect humoral immune responses against the latent EBV antigen EBNA1 in RRMS.

  15. Dexamethasone Enhances 1α,25-Dihydroxyvitamin D3 Effects by Increasing Vitamin D Receptor Transcription*

    Science.gov (United States)

    Hidalgo, Alejandro A.; Deeb, Kristin K.; Pike, J. Wesley; Johnson, Candace S.; Trump, Donald L.

    2011-01-01

    Calcitriol, the active form of vitamin D, in combination with the glucocorticoid dexamethasone (Dex) has been shown to increase the antitumor effects of calcitriol in squamous cell carcinoma. In this study we found that pretreatment with Dex potentiates calcitriol effects by inhibiting cell growth and increasing vitamin D receptor (VDR) and VDR-mediated transcription. Treatment with actinomycin D inhibits Vdr mRNA synthesis, indicating that Dex regulates VDR expression at transcriptional level. Real time PCR shows that treatment with Dex increases Vdr transcripts in a time- and a dose-dependent manner, indicating that Dex directly regulates expression of Vdr. RU486, an inhibitor of glucocorticoids, inhibits Dex-induced Vdr expression. In addition, the silencing of glucocorticoid receptor (GR) abolishes the induction of Vdr by Dex, indicating that Dex increases Vdr transcripts in a GR-dependent manner. A fragment located 5.2 kb upstream of Vdr transcription start site containing two putative glucocorticoid response elements (GREs) was evaluated using a luciferase-based reporter assay. Treatment with 100 nm Dex induces transcription of luciferase driven by the fragment. Deletion of the GRE distal to transcription start site was sufficient to abolish Dex induction of luciferase. Also, chromatin immunoprecipitation reveals recruitment of GR to distal GRE with Dex treatment. We conclude that Dex increases VDR and vitamin D effects by increasing Vdr de novo transcription in a GR-dependent manner. PMID:21868377

  16. Influence of vitamins A, D3 and E status on post-mortem meat quality in steers under winter housing or pasture finishing systems

    DEFF Research Database (Denmark)

    Turner, T; Pickova, J; Ertbjerg, P

    2011-01-01

    We investigated the influence of Swedish recommended vitamins A, D3 and E supplementation levels on muscle tenderness and fatty acid (FA) composition under indoor or outdoor finishing programmes. Swedish Red breed steer calves were divided into vitamin supplemented (n512) and non-supplemented (n515......) groups while on pasture prior to the finishing period. This trial began at the beginning of the winter housing period during which the steers were fed a 55 : 45 dry matter barley : grass silage diet indoors. The indoor finished group was comprised of vitamin supplemented (n56) and non-supplemented (n58......) steers slaughtered after about 155 days on feed. Vitamin supplemented steers were provided with 100 g mineral supplement providing 400 000 IU vitamin A, 100 000 IU D3 and 3000 IU E daily as recommended for Swedish production practices. In spring, outdoor finished vitamin supplemented (n56) and non...

  17. Integrated backscatter for the in vivo quantification of supraphysiological vitamin D(3)-induced cardiovascular calcifications in rats.

    Science.gov (United States)

    Roosens, Bram; Droogmans, Steven; Hostens, Jeroen; Somja, Joan; Delvenne, Eléonore; Hernot, Sophie; Bala, Gezim; Degaillier, Céline; Caveliers, Vicky; Delvenne, Philippe; Lahoutte, Tony; Van Camp, Guy; Cosyns, Bernard

    2011-09-01

    Cardiovascular calcifications are frequently found in the aging population and are independent predictors of future cardiovascular events. Integrated backscatter (IB) of ultrasound reflectivity can easily quantify calcifications. For this purpose, 30 male Wistar rats received 25,000 IU/kg/day of vitamin D(3) (group 1, n = 8), 18,800 IU/kg/day (group 2, n = 8), or injections with the vehicle only (group 3, n = 14), for 10 weeks. Echocardiographic calibrated IB (cIB) was measured and calculated at baseline and after 10 weeks, followed by ex vivo micro-CT and histopathology of the aortic valve, ascending aorta, and myocardium. After 10 weeks, the mean cIB value of the aortic valve was significantly higher for vitamin D(3)-dosed animals compared to controls. The mean cIB value of the ascending aorta and the myocardium was also significantly higher in group 1 compared to group 3. In vivo IB results were confirmed by ex vivo micro-CT and histopathology. In conclusion, IB is a non-ionizing, feasible, and reproducible tool to quantify cardiovascular calcifications in an in vivo rat model. The integration of IB in the standard echocardiographic examination for the quantification of cardiovascular calcifications could be useful for serial evaluation of treatment efficacy and for prognosis assessment.

  18. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial.

    Science.gov (United States)

    Murdoch, David R; Slow, Sandy; Chambers, Stephen T; Jennings, Lance C; Stewart, Alistair W; Priest, Patricia C; Florkowski, Christopher M; Livesey, John H; Camargo, Carlos A; Scragg, Robert

    2012-10-03

    Observational studies have reported an inverse association between serum 25-hydroxyvitamin D (25-OHD) levels and incidence of upper respiratory tract infections (URTIs). However, results of clinical trials of vitamin D supplementation have been inconclusive. To determine the effect of vitamin D supplementation on incidence and severity of URTIs in healthy adults. Randomized, double-blind, placebo-controlled trial conducted among 322 healthy adults between February 2010 and November 2011 in Christchurch, New Zealand. Participants were randomly assigned to receive an initial dose of 200,000 IU oral vitamin D3, then 200,000 IU 1 month later, then 100,000 IU monthly (n = 161), or placebo administered in an identical dosing regimen (n = 161), for a total of 18 months. The primary end point was number of URTI episodes. Secondary end points were duration of URTI episodes, severity of URTI episodes, and number of days of missed work due to URTI episodes. The mean baseline 25-OHD level of participants was 29 (SD, 9) ng/mL. Vitamin D supplementation resulted in an increase in serum 25-OHD levels that was maintained at greater than 48 ng/mL throughout the study. There were 593 URTI episodes in the vitamin D group and 611 in the placebo group, with no statistically significant differences in the number of URTIs per participant (mean, 3.7 per person in the vitamin D group and 3.8 per person in the placebo group; risk ratio, 0.97; 95% CI, 0.85-1.11), number of days of missed work as a result of URTIs (mean, 0.76 days in each group; risk ratio, 1.03; 95% CI, 0.81-1.30), duration of symptoms per episode (mean, 12 days in each group; risk ratio, 0.96; 95% CI, 0.73-1.25), or severity of URTI episodes. These findings remained unchanged when the analysis was repeated by season and by baseline 25-OHD levels. In this trial, monthly administration of 100,000 IU of vitamin D did not reduce the incidence or severity of URTIs in healthy adults. anzctr.org.au Identifier: ACTRN12609000486224.

  19. Effect of monthly vitamin D3 supplementation in healthy adults on adverse effects of earthquakes: randomised controlled trial.

    Science.gov (United States)

    Slow, Sandy; Florkowski, Christopher M; Chambers, Stephen T; Priest, Patricia C; Stewart, Alistair W; Jennings, Lance C; Livesey, John H; Camargo, Carlos A; Scragg, Robert; Murdoch, David R

    2014-12-15

    To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes. Opportunistic addition to an established randomised double blind placebo controlled trial. Christchurch, New Zealand, where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred, which caused widespread destruction, fatalities, and extensive psychological damage. 322 healthy adults (241 women; 81 men) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study (VIDARIS) between February 2010 and November 2011. Participants were randomised to receive an oral dose of either 200,000 IU vitamin D3 monthly for two months then 100,000 IU monthly (n=161) or placebo (n=161) for a total of 18 months. This is a post hoc analysis from the previously published VIDARIS trial. The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011, which was used as the index event. The secondary end point was the number of "psychological" adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial. 308 participants completed the earthquake impact questionnaire (n=152 in the vitamin D group and 156 in the placebo group). There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo. There was also no difference in the overall adverse impact score between treatment groups (χ(2) P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; χ(2) P=0.03). The number of psychological adverse events-such as fatigue, stress, anxiety, and insomnia-that participants reported at their usual monthly appointments was significantly

  20. Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome--a randomised controlled trial.

    Science.gov (United States)

    Witham, M D; Adams, F; McSwiggan, S; Kennedy, G; Kabir, G; Belch, J J F; Khan, F

    2015-03-01

    Low 25-hydroxyvitamin D levels are common in patients with chronic fatigue syndrome; such patients also manifest impaired vascular health. We tested whether high-dose intermittent oral vitamin D therapy improved markers of vascular health and fatigue in patients with chronic fatigue syndrome. Parallel-group, double-blind, randomised placebo-controlled trial. Patients with chronic fatigue syndrome according to the Fukuda (1994) and Canadian (2003) criteria were randomised to receive 100,000 units oral vitamin D3 or matching placebo every 2 months for 6 months. The primary outcome was arterial stiffness measured using carotid-femoral pulse wave velocity at 6 months. Secondary outcomes included flow-mediated dilatation of the brachial artery, blood pressure, cholesterol, insulin resistance, markers of inflammation and oxidative stress, and the Piper Fatigue scale. As many as 50 participants were randomised; mean age 49 (SD 13) years, mean baseline pulse wave velocity 7.8 m/s (SD 2.3), mean baseline office blood pressure 128/78 (18/12) mmHg and mean baseline 25-hydroxyvitamin D level 46 (18) nmol/L. 25-hydroxyvitamin D levels increased by 22 nmol/L at 6 months in the treatment group relative to placebo. There was no effect of treatment on pulse wave velocity at 6 months (adjusted treatment effect 0.0 m/s; 95% CI -0.6 to 0.6; p = 0.93). No improvement was seen in other vascular and metabolic outcomes, or in the Piper Fatigue scale at 6 months (adjusted treatment effect 0.2 points; 95% CI -0.8 to 1.2; p = 0.73). High-dose oral vitamin D3 did not improve markers of vascular health or fatigue in patients with chronic fatigue syndrome. www.controlled-trials.com, ISRCTN59927814. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Neuroprotective and immune effects of active forms of vitamin D3 and docosahexaenoic acid in Alzheimer disease patients

    Directory of Open Access Journals (Sweden)

    Milan Fiala

    2011-12-01

    Full Text Available ABSTRACT:Neurodegenerative diseases, in particular Alzheimer disease (AD, afflict an increasing proportion of the older population with aging. Decreased exposure to sunlight and decreased consumption of fish, fruits, and vegetables, are two epidemiological factors that appear to be related to the pandemic of AD. In addition to replacing simple with complex carbohydrates and avoiding saturated fat, two nutritional components, vitamin D (acting through the endogenous hormonal form 1,25 dihydroxyvitamin D, 1,25D and docosahexaenoic acid (DHA (acting through the docosanoid lipidic modulators resolvins and neuroprotectins have high potential for prevention of Alzheimer disease. 1,25D is a neuroprotective, it acts both directly and indirectly in neurons by improving the clearance of amyloid-beta by macrophages/microglia. Resolvins and neuroprotectins inhibit amyloidogenic processing of amyloid-precursor protein, inflammatory cytokines, and apoptosis. It is likely that the increased consumption of vitamin D and fish oil could prevent neurodegeneration in some subjects by maintaining adequate endocrine, paracrine, and/or autocrine production of 1,25D and the DHA-derived lipidic modulators. Before firm recommendations of the dosage can be proposed, however, the in vivo effects of vitamin D3 and DHA supplementation should be investigated by prospective studies.

  2. The effect of calcium and vitamin D3 supplementation on the healing of the proximal humerus fracture: a randomized placebo-controlled study

    DEFF Research Database (Denmark)

    Doetsch, A M; Faber, J; Lynnerup, N

    2004-01-01

    The purpose of this study was to (1) quantify the healing process of the human osteoporotic proximal humerus fracture (PHF) expressed in terms of callus formation over the fracture region using BMD scanning, and (2) quantify the impact of medical intervention with vitamin D3 and calcium...... demonstrated that it is possible to quantify callus formation of the PHF with sufficiently high precision to demonstrate the positive influence of vitamin D3 and calcium over the first 6 weeks after fracture. Whether this results in more stable fractures, extends to other fracture types, or applies to other...... scan, WHO criteria), and not taking any drugs related to bone formation, including calcium or vitamin D supplementation, were randomly assigned to either oral 800 IU vitamin D3 plus 1 g calcium or placebo, in a double-blind prospective study. We measured biochemical, radiographic, and bone mineral...

  3. Time-course analysis of 3-epi-25-hydroxyvitamin D3 shows markedly elevated levels in early life, particularly from vitamin D supplementation in preterm infants.

    Science.gov (United States)

    Ooms, Nina; van Daal, Henny; Beijers, Antonius M; Gerrits, G Peter J M; Semmekrot, Ben A; van den Ouweland, Johannes M W

    2016-04-01

    An epimeric form of 25-hydroxyvitamin D3 (25(OH)D3) has recently been detected in clinical samples, with relatively high levels in infants. Little is known on 3-epi-25(OH)D3 formation and physiological function. Our objective was to study dynamics of 3-epi-25(OH)D3 formation during infancy. 25(OH)D3 and 3-epi-25(OH)D3 levels were measured by liquid chromatography-tandem mass spectrometry in 22 preterm (aged 34-37 wk), 15 early preterm (aged epi-25(OH)D3 levels were 3 (1-7) nmol/l, epi-25(OH)D3 increased, with highest 3-epi-25(OH)D3 contribution in early preterm infants (up to 55% of total 25(OH)D3 vs. 36% in term infants, P epi-25(OH)D3 normalized to epi-25(OH)D3, increasing the week after starting vitamin D supplementation, until 3 mo of age. Highest levels of 3-epi-25(OH)D3 were found in early preterm infants, supporting the hypothesis that hepatic immaturity plays a role in 3-epi-25(OH)D3 formation.

  4. Vitamin D3 and Monomethyl Fumarate Enhance Natural Killer Cell Lysis of Dendritic Cells and Ameliorate the Clinical Score in Mice Suffering from Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Zaidoon Al-Jaderi

    2015-11-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is a CD4+ T cell mediated inflammatory demyelinating disease that is induced in mice by administration of peptides derived from myelin proteins. We developed EAE in SJL mice by administration of PLP139–151 peptide. The effect of treating these mice with 1α,25-Dihydroxyvitamin D3 (vitamin D3, or with monomethyl fumarate (MMF was then examined. We observed that both vitamin D3 and MMF inhibited and/or prevented EAE in these mice. These findings were corroborated with isolating natural killer (NK cells from vitamin D3-treated or MMF-treated EAE mice that lysed immature or mature dendritic cells. The results support and extend other findings indicating that an important mechanism of action for drugs used to treat multiple sclerosis (MS is to enhance NK cell lysis of dendritic cells.

  5. 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

    OpenAIRE

    Bischoff-Ferrari HA Dawson-Hughes B Stöcklin E Sidelnikov E Willett WC Edel JO Stähelin HB W

    2012-01-01

    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 13.2?±?3.9?ng/mL (mean?±?SD) and a mean age of 61.5?±?7.2 years were randomized to either 20?µg of HyD or 20?µg (800?IU) of vitamin D3 per day in a double blind manner. We measured on 14 visits over 4 months 25(OH)D serum levels blood pressure and se...

  6. The effect of combined resistance exercise training and vitamin D3 supplementation on musculoskeletal health and function in older adults: a systematic review and meta-analysis.

    Science.gov (United States)

    Antoniak, Anneka Elizabeth; Greig, Carolyn A

    2017-07-20

    In older adults, there is a blunted responsiveness to resistance training and reduced muscle hypertrophy compared with younger adults. There is evidence that both exercise training and vitamin D supplementation may benefit musculoskeletal health in older adults, and it is plausible that in combination their effects may be additive. The aim of this systematic review was to evaluate the effectiveness of combined resistance exercise training and vitamin D3 supplementation on musculoskeletal health in older adults. A comprehensive search of electronic databases, including Science Direct, Medline, PubMed, Google Scholar and Cochrane Central Register of Controlled Trials (Cochrane CENTRAL accessed by Wiley Science) was conducted. Eligible studies were randomised controlled trials including men and women (aged ≥65 years or mean age ≥65 years); enlisting resistance exercise training and vitamin D3 supplementation; including outcomes of muscle strength, function, muscle power, body composition, serum vitamin D/calcium status or quality of life comparing results with a control group. The review was informed by a preregistered protocol (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015020157). Seven studies including a total of 792 participants were identified. Studies were categorised into two groups; group 1 compared vitamin D3 supplementation and exercise training versus exercise alone (describing the additive effect of vitamin D3 supplementation when combined with resistance exercise training) and group 2 compared vitamin D3 supplementation and exercise training versus vitamin D3 supplementation alone (describing the additive effect of resistance exercise training when combined with vitamin D3 supplementation).Meta-analyses for group 1 found muscle strength of the lower limb to be significantly improved within the intervention group (0.98, 95% CI 0.73 to 1.24, pvitamin D3 supplementation for the improvement of muscle strength in older adults. For

  7. Maintenance vitamin D3 dosage requirements in Chinese women with post menopausal osteoporosis living in the tropics.

    Science.gov (United States)

    Venugopal, Yogeswari; Hatta, Sharifah F Wan Muhamad; Musa, Nurbazlin; Rahman, Siti Abdul; Ratnasingam, Jeyakantha; Paramasivam, Sharmila Sunita; Lim, Lee Ling; Ibrahim, Luqman; Choong, Karen; Tan, Alexander Tb; Chinna, Karuthan; Chan, Siew Pheng; Vethakkan, Shireene R

    2017-05-01

    Vitamin D3 (cholecalciferol) dose required to maintain sufficiency in non- Caucasian women with postmenopausal osteoporosis (PMO) inthe tropics has not been well studied. Some guidelines mandate 800-1000 IU vitamin D/day but the Endocrine Society (US) advocates 1500-2000 IU/day to maintain 25-hydroxyvitamin-D (25(OH)D) concentration at >75 nmol/L. We aimed to establish oral cholecalciferol dose required to maintain 25(OH)D concentration at >75 nmol/L in PMO Chinese Malaysian women, postulating lower dose requirements amongst light-skinned subjects in the tropics. 90 Chinese Malaysian PMO women in Kuala Lumpur, Malaysia (2°30'N) with baseline serum 25(OH)D levels >=50 nmol/L were recruited. Prior vitamin D supplements were discontinued and subjects randomized to oral cholecalciferol 25,000 IU/4-weekly (Group-A) or 50,000 IU/4-weekly (Group- B) for 16 weeks, administered under direct observation. Serum 25(OH)D, PTH, serum/urinary calcium were measured at baseline, 8 and 16 weeks. Baseline characteristics, including osteoporosis severity, sun exposure (~3 hours/week), and serum 25(OH)D did not differ between treatment arms. After 16 weeks, 91% of women sufficient at baseline, remained sufficient on 25,000 IU/4-weekly compared with 97% on 50,000 IU/4-weekly with mean serum 25(OH)D 108.1±20.4 and 114.7±18.4 SD nmol/L respectively (p=0.273). At trial's end, 39% and 80% of insufficient women at baseline attained sufficiency in Group A and Group B (p=0.057). Neither dose was associated with hyperparathyroidism or toxicity. Despite pretrial vitamin D supplementation and adequate sun exposure, 25.6% Chinese Malaysian PMO women were vitamin D insufficient indicating sunshine alone cannot ensure sufficiency in the tropics. Both ~900 IU/day and ~1800 IU/day cholecalciferol can safely maintain vitamin D sufficiency in >90% of Chinese Malaysian PMO women. Higher doses are required with baseline concentration <75 nmol/L.

  8. Vitamin D3 Supplementation and Antibiotic Consumption - Results from a Prospective, Observational Study at an Immune-Deficiency Unit in Sweden.

    Directory of Open Access Journals (Sweden)

    Anna-Carin Norlin

    Full Text Available 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.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.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.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.

  9. Efficacy of 25-OH Vitamin D3 prophylactic administration for reducing lameness in broilers grown on wire flooring.

    Science.gov (United States)

    Wideman, R F; Blankenship, J; Pevzner, I Y; Turner, B J

    2015-08-01

    Bacterial chondronecrosis with osteomyelitis (BCO) is the most common cause of lameness in commercial broilers. Growing broilers on wire flooring provides an excellent experimental model for reproducibly triggering significant levels of lameness attributable to BCO. In the present study we evaluated the efficacy of adding HyD (25-OH vitamin D3) to the drinking water as a preventative/prophylactic treatment for lameness. Broiler chicks were reared on 5 x 10 ft flat wire floor panels within 6 environmental chambers. Three chambers were supplied with tap water (Control group) and the remaining chambers were supplied with HyD (HyD group: 0.06 mL HyD solution/L water; dosing based on the HyD Solution label to provide 33.9 μg 25-OHD3/L) from d 1 through 56. Feed was provided ad libitum and was formulated to meet or exceed minimum standards for all ingredients, including 5,500 IU vitamin D3/kg. Lameness initially was detected on d 28, and the cumulative incidence of lameness on d 56 was higher in the Control group than in the HyD group (34.7 vs. 22.7%, respectively; P = 0.03; Z-test of proportions; chambers pooled). The most prevalent diagnoses for lame birds were osteochondrosis and osteomyelitis (BCO) of the proximal femora (52%) and tibiae (79%), accompanied by minor incidences of tibial dyschondroplasia (0.33%), spondylolisthesis, or kinky back (0.67%), and twisted legs (1%). Broilers that survived to d 56 without developing lameness did not differ in BW when compared by group within a gender. The wire flooring model imposes a rigorous, sustained challenge that undoubtedly is much more severe than typically would be experienced by broilers under normal commercial conditions. Therefore the encouraging response to HyD supplementation in the present study supports the potential for 25-OH vitamin D3 to attenuate outbreaks of lameness caused by BCO in commercial broiler flocks. © 2015 Poultry Science Association Inc.

  10. ¿Es equivalente la suplementación diaria con vitamina D2 o vitamina D3 en adultos mayores? Is daily supplementation with vitamin D2 equivalent to daily supplementation with vitamin D3 in the elderly?

    Directory of Open Access Journals (Sweden)

    Mariana Seijo

    2012-06-01

    Full Text Available Tanto la equivalencia entre colecalciferol (D3 y ergocalciferol (D2, como las dosis y forma de administración de ambos, son actualmente un tema controvertido. El objetivo de este estudio fue comparar la efectividad de 800 UI/día de D2 (gotas y D3 (comprimidos para alcanzar niveles adecuados de 25 hidroxivitamina D (25OHD (= 30 ng/ml. Veintiún mujeres posmenopáusicas que vivían en la Ciudad de Buenos Aires, edad promedio ( ± DS 77.1 ± 6.8 años fueron incluidas y asignadas en forma aleatoria a uno de los siguientes grupos: GD2 (n = 13: 800 UI (gotas y GD3 (n = 8: 800 UI (comprimidos. Se midió 25OHD sérica (RIA-DIASORIN basal y a los 7, 28 y 45 días del estudio. Basalmente, 19 de las 21 mujeres presentaron niveles de deficiencia de 25(OHD (The equivalence of cholecalciferol (D3 and ergocalciferol (D2 as well as their corresponding doses and administration route remain controversial to date. The aim of this study was to compare the effectiveness of daily supplementation with 800 IU of D2 (drops and D3 (pills on 25-hydroxivitamin D (25OHD levels (= 30 ng/ml. Twenty-one ambulatory postmenopausal women from Buenos Aires City with a mean ( ± SD age of 77.1 ± 6.8 years were included. The participants were randomly assigned to one of the following groups: GD2 (n = 13: 800 IU (drops and GD3 (n = 8: 800 IU (pills. Serum 25OHD levels were measured (RIA-DIASORIN at baseline, and at 7, 28 and 45 days. Nineteen out of twenty one women showed deficient levels of 25OHD at baseline (< 20 ng/ml: GD2: 14.0 ± 4.8 ng/ml and GD3: 13.2 ± 4.9 ng/ml (NS. Whereas only GD3 exhibited an increase (~25% at 7 days, both groups showed a significant increase at the end of the study. However, neither attained adequate 25OHD levels (GD2: 17.4 ± 5.5 vs. GD3:22.9 ± 4.6 ng/ml; p < 0.001. Administration of 800 IU of vitamin D3 during 45 days was more effective than D2 in increasing 25OHD, but both failed to achieve adequate levels of 25OHD (= 30 ng/ml. but neither

  11. Evidence That Loss-of-Function Filaggrin Gene Mutations Evolved in Northern Europeans to Favor Intracutaneous Vitamin D3 Production

    DEFF Research Database (Denmark)

    Thyssen, Jacob P; Bikle, Daniel D; Elias, Peter M

    2014-01-01

    Skin pigmentation lightened progressively to a variable extent, as modern humans emigrated out of Africa, but extreme lightening occurred only in northern Europeans. Yet, loss of pigmentation alone cannot suffice to sustain cutaneous vitamin D3 (VD3) formation at the high latitudes of northern...... UV-B penetration and intracutaneous VD3 formation, the latitude-dependent gradient in FLG mutations, likely together with other concurrent mutations in VD3 metabolic pathways, provide a non-pigment-based mechanism that sustains higher levels of circulating VD3 in northern Europeans. At the time...... that FLG mutations evolved, xerosis due to FLG deficiency was a lesser price to pay for enhanced VD3 production. Yet, the increase in FLG mutations has inadvertently contributed to an epidemic of atopic diseases that has emerged in recent decades....

  12. Four-year clinical remission of type 1 diabetes mellitus in two patients treated with sitagliptin and vitamin D3

    Directory of Open Access Journals (Sweden)

    Marcelo Maia Pinheiro

    2016-12-01

    Full Text Available Type 1 diabetes mellitus (T1DM is a chronic disease characterized by autoimmune destruction of pancreatic beta cells and inadequate insulin production. Remission criteria in T1DM take into account serum levels of C-peptide and glycosylated hemoglobin, as well as the dose of insulin administered to the patient. However, remission of T1DM lasting longer than 1 year is rare. We describe here the cases of two young women who presented with positive glutamic acid decarboxylase (GAD antibody and classic clinical manifestations of T1DM. Both patients had a prior history of Hashimoto’s thyroiditis. They were initially treated with a basal-bolus regimen of insulin (glargine and lispro/glulisine. Once their blood glucose levels were controlled, they were started on oral sitagliptin 100 mg and vitamin D3 5000 IU daily. After this therapy, both patients achieved clinical diabetes remission for 4 years, along with a decrease in anti-GAD antibody levels. These benefits were probably associated with immunological effects of these medications. Inhibition of dipeptidyl peptidase 4 (DPP-4 in animal models deregulates Th1 immune response, increases secretion of Th2 cytokines, activates CD4+CD25+FoxP3+ regulatory T-cells and prevents IL-17 production. Vitamin D3 also activates CD4+CD25+FoxP3+ regulatory T-cells, and these medications combined can improve the immune response in patients with new-onset T1DM and probably promote sustained clinical remission.

  13. Glucose-induced insulin secretion in uremia: role of 1 alpha,25(HO)2-vitamin D3.

    Science.gov (United States)

    Allegra, V; Luisetto, G; Mengozzi, G; Martimbianco, L; Vasile, A

    1994-01-01

    To evaluate the role and mechanism of action of calcitriol on glucose-induced insulin secretion in uremia, 17 patients with severe chronic renal failure were studied. Glucose metabolism was investigated by the intravenous glucose tolerance test (IVGTT) before and after treatment for 21 days with 0.5 microgram/day of calcitriol and 500 mg/day of calcium (C+Ca) (6 cases) or 0.5 microgram/day of calcitriol alone (C) (11 cases). After these evaluations the patients on C+Ca were shifted to C and 6 patients on C were shifted to C+Ca, and IVGTT was repeated 21 days after the shift. For each test plasma glucose (G), immunoreactive insulin (IRI) and C-peptide (C-p) were measured at -30, 0, 2, 5, 15, 30, 45, 60 min, and baseline plasma values of 1 alpha,25(HO)2-vitamin D3, C-terminal parathyroid hormone (PTH-C), intact parathyroid hormone (PTH-I), calcitonin, and serum values of total and ionized calcium were dosed. Also, glucose constant decay (K-G), insulin response (IRI area), C-p production (C-p area), insulinogenic index (IGI) and insulin resistance index (RI) were calculated. A historical group of 21 healthy volunteers formed the normal controls. 1 alpha,25(HO)2-vitamin D3 plasma levels in uremic patients before treatment were significantly lower than normal range. As compared to controls, uremic patients showed significantly lower K-G, IRI area and IGI values and significantly higher RI values. After treatment with C or C+Ca, the insulin response improved significantly at 2 and 5 min and G decrement was more marked at 30, 45 and 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Combination of vitamin B12 active forms improved fetal growth in Wistar rats through up-regulation of placental miR-16 and miR-21 levels.

    Science.gov (United States)

    Shah, Tejas; Mishra, Sanjay; More, Amol; Otiv, Suhas; Apte, Kishori; Joshi, Kalpana

    2017-12-15

    Epidemiological studies have indicated importance of folate and vitamin (B12) during pregnancy. Also available evidence on efficacy of B12 forms viz. Cyanocobalamin (Cbl), Methylcobalamin (MeCbl), Adenosylcobalamin (AdCbl) and Hydroxycobalamin (HCbl) in preventing or treating cobalamin deficiency is limited. The present study examines the effect of various forms of B12 in combination with folate during pregnancy and their effect on gestational outcomes. In the present study, we examined the effect of various vitamin B12 forms in presence of recommended folate (RFol: 400μg/day) and high folate (HFol: 5mg/day) on gestational outcomes in female Wistar rats. Dams dosed with excessive folate (HFol group) delivered low birth weight (LBW) offsprings (pB12 supplementation. Excessive folate supplementation and homocysteine levels showed inverse association with placental weight (pB12 supplementation significantly up-regulated placental miR-16 and miR-21, associated with fetal growth which in turn reflected in improved birthweights. Supplementation with vitamin B12 forms, especially combination of active forms of cobalamins: MeCbl+AdCbl significantly increased birth weights (pB12 along with folate during pregnancy had positive impact on the gestational outcomes. We have shown for the first time that combination of active forms of vitamin B12: MeCbl+AdCbl has better efficacy as compared to Cbl, MeCbl, AdCbl and HCbl alone. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The effect of a single oral megadose of vitamin D provided as either ergocalciferol (D2) or cholecalciferol (D3) in alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Knudsen, Mikkel Malham; Jørgensen, S. P.; Lauridsen, A. L.

    2012-01-01

    Objective: The goal of this study was to examine the effects of a single oral dose of 300 000 international units of either ergocalciferol (D2) or cholecalciferol (D3) on the plasma levels of 25-hydroxyvitamin D in patients with alcoholic liver cirrhosis. Methods: Inclusion criteria for this stud...... cirrhosis, a single oral megadose of cholecalciferol was more effective than ergocalciferol in the treatment of vitamin D deficiency. Severe liver disease and low levels of vitamin D-binding protein were predictors for poor treatment outcomes.......=13). Plasma concentrations of 25(OH) vitamin D and vitamin D-binding protein were measured on days 0, 7, 30, and 90. Results: On days 7 and 30, patients from the D3 group had higher vitamin D levels than patients from the D2 group (Pvitamin D levels were found to correlate...... with Child–Pugh scores from patients in the D3 group. For patients in the D2 group, there was a positive correlation between vitamin D and vitamin D-binding protein as indicated by the area under the concentration versus time curves (Spearmen’s ρ=0.64 P

  16. High-dose vitamin D3 reduces deficiency caused by low UVB exposure and limits HIV-1 replication in urban Southern Africans

    Science.gov (United States)

    Coussens, Anna K.; Naude, Celeste E.; Goliath, Rene; Chaplin, George; Wilkinson, Robert J.; Jablonski, Nina G.

    2015-06-01

    Cape Town, South Africa, has a seasonal pattern of UVB radiation and a predominantly dark-skinned urban population who suffer high HIV-1 prevalence. This coexistent environmental and phenotypic scenario puts residents at risk for vitamin D deficiency, which may potentiate HIV-1 disease progression. We conducted a longitudinal study in two ethnically distinct groups of healthy young adults in Cape Town, supplemented with vitamin D3 in winter, to determine whether vitamin D status modifies the response to HIV-1 infection and to identify the major determinants of vitamin D status (UVB exposure, diet, pigmentation, and genetics). Vitamin D deficiency was observed in the majority of subjects in winter and in a proportion of individuals in summer, was highly correlated with UVB exposure, and was associated with greater HIV-1 replication in peripheral blood cells. High-dosage oral vitamin D3 supplementation attenuated HIV-1 replication, increased circulating leukocytes, and reversed winter-associated anemia. Vitamin D3 therefore presents as a low-cost supplementation to improve HIV-associated immunity.

  17. 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.

    Science.gov (United States)

    Bischoff-Ferrari, Heike Annette; Dawson-Hughes, Bess; Stöcklin, Elisabeth; Sidelnikov, Eduard; Willett, Walter Churchill; Edel, John Orav; Stähelin, Hannes Balthasar; Wolfram, Swen; Jetter, Alexander; Schwager, Joseph; Henschkowski, Jana; von Eckardstein, Arnold; Egli, Andreas

    2012-01-01

    To test the effect of 25(OH)D(3) (HyD) compared to vitamin D(3) 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 13.2 ± 3.9 ng/mL (mean ± SD) and a mean age of 61.5 ± 7.2 years were randomized to either 20 µg of HyD or 20 µg (800 IU) of vitamin D(3) per day in a double-blind manner. We measured on 14 visits over 4 months, 25(OH)D serum levels, blood pressure, and seven markers of innate immunity (eotaxin, interleukin [IL]-8, IL-12, interferon gamma-induced protein 10 kDa [IP-10], monocyte chemotactic protein-1 [MCP-1], macrophage inflammatory protein beta [MIP-1β], and "Regulated upon Activation, Normal T-cell Expressed, and Secreted" [RANTES]). At baseline and at 4 months, a test battery for lower extremity function (knee extensor and flexor strength, timed up and go, repeated sit-to-stand) was assessed. All analyses were adjusted for baseline measurement, age, and body mass index. Mean 25(OH)D levels increased to 69.5 ng/mL in the HyD group. This rise was immediate and sustained. Mean 25(OH)D levels increased to 31.0 ng/mL with a slow increase in the vitamin D(3) group. Women on HyD compared with vitamin D(3) had a 2.8-fold increased odds of maintained or improved lower extremity function (odds ratio [OR] = 2.79; 95% confidence interval [CI], 1.18-6.58), and a 5.7-mmHg decrease in systolic blood pressure (p = 0.0002). Both types of vitamin D contributed to a decrease in five out of seven markers of innate immunity, significantly more pronounced with HyD for eotaxin, IL-12, MCP-1, and MIP-1 β. There were no cases of hypercalcemia at any time point. Twenty micrograms (20 µg) of HyD per day resulted in a safe, immediate, and sustained increase in 25(OH)D serum levels in all participants, which may explain its significant benefit on lower extremity function, systolic blood pressure

  18. Effects of High-Dose Vitamin D2 Versus D3 on Total and Free 25-Hydroxyvitamin D and Markers of Calcium Balance

    Science.gov (United States)

    Chun, Rene F.; Ma, Christina; Witzel, Sten; Meyer, Briana; Rafison, Brandon; Swinkels, Leon; Huijs, Tonnie; Pepkowitz, Sam; Holmquist, Brett; Hewison, Martin; Adams, John S.

    2016-01-01

    Context: Controversy persists over: 1) how best to restore low serum 25-hydroxyvitamin D (25D) levels (vitamin D2 [D2] vs vitamin D3 [D3]); 2) how best to define vitamin D status (total [protein-bound + free] vs free 25D); and 3) how best to assess the bioactivity of free 25D. Objective: To assess: 1) the effects of D2 vs D3 on serum total and free 25D; and 2) whether change in intact PTH (iPTH) is more strongly associated with change in total vs free 25D. Design: Participants previously enrolled in a D2 vs D3 trial were matched for age, body mass index, and race/ethnicity. Participants received 50 000 IU of D2 or D3 twice weekly for 5 weeks, followed by a 5-week equilibration period. Biochemical assessment was performed at baseline and at 10 weeks. Setting and Participants: Thirty-eight adults (19 D2 and 19 D3) ≥18 years of age with baseline 25D levels P = .5) and free (5.4 ± 0.8 vs 5.3 ± 1.7 pg/mL; P = .8) 25D levels were similar between D2 and D3 groups. Increases in total (+27.6 vs +12.2 ng/mL; P = .001) and free (+3.6 vs +6.2 pg/mL; P = .02) 25D levels were greater with D3 vs D2. Percentage change in iPTH was significantly associated with change in free (but not total) 25D, without and with adjustment for supplementation regimen, change in 1,25-dihydroxyvitamin D, and change in calcium. Conclusions: D3 increased total and free 25D levels to a greater extent than D2. Free 25D may be superior to total 25D as a marker of vitamin D bioactivity. PMID:27192696

  19. Short-term vitamin D3 supplementation lowers plasma renin activity in patients with stable chronic heart failure : An open-label, blinded end point, randomized prospective trial (VitD-CHF trial)

    NARCIS (Netherlands)

    Schroten, Nicolas F; Ruifrok, Willem P T; Kleijn, Lennaert; Dokter, Martin M; Silljé, Herman H; Lambers Heerspink, Hiddo J; Bakker, Stephan J L; Kema, Ido; van Gilst, Wiek H; van Veldhuisen, Dirk J; Hillege, Hans L; de Boer, Rudolf A

    Background Many chronic heart failure (CHF) patients have low vitamin D (VitD) and high plasma renin activity (PRA), which are both associated with poor prognosis. Vitamin D may inhibit renin transcription and lower PRA. We investigated whether vitamin D3 (VitD3) supplementation lowers PRA in CHF

  20. Effects of dietary addition of vitamins C and D3 on growth and calcium and phosphorus content of pond-cultured channel catfish

    Science.gov (United States)

    Launer, C.A.; Tiemeier, O.W.; Deyoe, C.W.

    1978-01-01

    Fingerling channel catfish, Ictalurus punctatus, were fed one of three diets: one deficient in vitamin C (ascorbic acid), one deficient in vitamin D3 (cholecalciferol), or one containing both vitamins. Semimonthly from May to September and monthly from September to February, calcium and phosphorus were determined in eviscerated bodies and fat-free skeletons by neutron activation analysis. Body weight gains, survival rate, and feed conversion rates were determined for the May to September period. Fish on the three diet regimens showed no significant difference in weight gain, feed conversion, or survival. Interactions between sampling date and diet indicated no correlation between vitamin C or D3 and the calcium and phosphorus in eviscerated bodies and fat-free skeletons of the fish.

  1. Endothelial relaxation mechanisms and nitrative stress are partly restored by Vitamin D3 therapy in a rat model of polycystic ovary syndrome.

    Science.gov (United States)

    Masszi, Gabriella; Benko, Rita; Csibi, Noemi; Horvath, Eszter M; Tokes, Anna-Maria; Novak, Agnes; Beres, Nora Judit; Tarszabo, Robert; Buday, Anna; Repas, Csaba; Bekesi, Gabor; Patocs, Attila; Nadasy, Gyorgy L; Hamar, Peter; Benyo, Zoltan; Varbiro, Szabolcs

    2013-08-06

    In polycystic ovary syndrome (PCOS), metabolic and cardiovascular dysfunction is related to hyperandrogenic status and insulin resistance, however, Vitamin D3 has a beneficial effect partly due to its anti-oxidant capacity. Nitrative stress is a major factor in the development of cardiovascular dysfunction and insulin resistance in various diseases. Our aim was to determine the effects of vitamin D3 in a rat model of PCOS, particularly the pathogenic role of nitrative stress. Female Wistar rats weighing 100-140g were administered vehicle (C), dihydrotestosterone (DHT) or dihydrotestosterone plus vitamin D3 (DHT+D) (n=10 per group). On the 10th week, acetylcholine (Ach) induced relaxation ability of the isolated thoracic aorta rings was determined. In order to examine the possible role of endothelial nitric oxide synthase (eNOS) and cyclooxygenase-2 (COX-2) pathways in the impaired endothelial function, immunohistochemical labeling of aortas with anti-eNOS and anti-COX-2 antibodies was performed. Leukocyte smears, aorta and ovary tissue sections were also immunostained with anti-nitrotyrosine antibody to determine nitrative stress. Relaxation ability of aorta was reduced in group DHT, and vitamin D3 partly restored Ach induced relaxation. eNOS labeling was significantly lower in DHT rats compared to the other two groups, however COX-2 staining showed an increment. Nitrative stress showed a significant increase in response to dihydrotestosterone, while vitamin D3 treatment, in case of the ovaries, was able to reverse this effect. Nitrative stress may play a role in the pathogenesis of PCOS and in the development of the therapeutic effect of vitamin D3. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Low vitamin D3 and high anti-Müllerian hormone serum levels in the polycystic ovary syndrome (PCOS): Is there a link?

    Science.gov (United States)

    Cappy, Hélène; Giacobini, Paolo; Pigny, Pascal; Bruyneel, Aude; Leroy-Billiard, Maryse; Dewailly, Didier; Catteau-Jonard, Sophie

    2016-10-01

    Low vitamin D serum level has been reported in women with polycystic ovary syndrome (PCOS) compared to controls. A few in vitro studies showed that the bioactive form of vitamin D is able to modulate the expression of the anti-Müllerian hormone (AMH) gene. However, in vivo studies failed to demonstrate clearly whether low vitamin D3 serum level is involved in the AMH excess of PCOS. This prospective study evaluates serum vitamin D3 and AMH levels in women with PCOS and in controls, before and after vitamin D supplementation. Among vitamin D deficient patients, 23 patients with PCOS were compared to 27 women with normal ovarian reserve (NOR). The vitamin D deficient patients received a vitamin D supplementation according to the depth of their insufficiency. For the 23 patients with PCOS and the 27 controls, serum AMH assay and serum calciotropic hormone assays [25-hydroxyvitamin D (25[OH]D), 1,25 dihydroxyvitamin D (1,25[OH] 2 D) and parathyroid hormone (PTH)] were performed before and after supplementation. Serum 25(OH)D levels before treatment were statistically lower in PCOS women than in NOR patients (PPCOS patients nor in NOR patients. In both groups, 25(OH)D serum levels were not related to serum AMH levels, serum 1,25(OH) 2 D and serum PTH levels, before and after treatment. We found no evidence that serum calciotropic hormones are linked to circulating AMH levels, particularly in PCOS. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Roth Daniel E

    2012-12-01

    Full Text Available Abstract 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

  4. The effect of combined resistance exercise training and vitamin D3 supplementation on musculoskeletal health and function in older adults: a systematic review and meta-analysis

    OpenAIRE

    Antoniak, Anneka Elizabeth; Greig, Carolyn A.

    2017-01-01

    Objectives In older adults, there is a blunted responsiveness to resistance training and reduced muscle hypertrophy compared with younger adults. There is evidence that both exercise training and vitamin D supplementation may benefit musculoskeletal health in older adults, and it is plausible that in combination their effects may be additive. The aim of this systematic review was to evaluate the effectiveness of combined resistance exercise training and vitamin D3 supplementation on musculosk...

  5. Acute Effects of Vitamin D3 Supplementation on Muscle Strength in Judoka Athletes: A Randomized Placebo-Controlled, Double-Blind Trial.

    Science.gov (United States)

    Wyon, Matthew A; Wolman, Roger; Nevill, Alan M; Cloak, Ross; Metsios, George S; Gould, Douglas; Ingham, Andrew; Koutedakis, Yiannis

    2016-07-01

    Indoor athletes have been shown to be prone to vitamin D3 deficiency. The aim of the study was to examine the acute effects of vitamin D supplementation on muscle function using isokinetic dynamometry. Randomized placebo-controlled, double-blind study. Institutional. Adult male white national level judoka athletes (n = 22) who were involved in full-time training. Exclusion criteria were vitamin supplementation, overseas travel to sunny climes, and/or an injury incurred during the last 3 months before testing. Subjects were randomly allocated to the treatment (150 000IU vitamin D3) or placebo and given blinded supplements by an independent researcher. Participants were tested twice, 8 days apart, on a Monday morning before the start of judo training and after 2 days of rest. A 5 to 7 mL of blood sample was collected followed by isokinetic concentric quadriceps and hamstring muscle function assessments on the right leg at 30 and 200°·s. Repeated-measures analysis of variance was used to analyze isokinetic muscle force and serum 25(OH)D3. Regression to the mean was used to examine changes in 25(OH)D3 levels over the study period. The treatment group demonstrated a significant increase in serum 25(OH)D levels (34%, P ≤ 0.001) and muscle strength (13%, P = 0.01) between days 1 and 8. No significant differences were found for the placebo group for the same period. A single bolus of 150 000IU vitamin D3 had a significant positive effect on serum 25(OH)D levels and muscle function in vitamin D insufficient elite indoor athletes. Serum 25(OH)D3 levels of indoor athletes should be monitored throughout the year and especially during winter months. Beneficial responses, in muscle strength and serum 25(OH)D3, to 1 dose of vitamin D3 supplementation can be observed within 1 week of ingestion. Muscle strength is linked to serum 25(OH)D levels.

  6. The lack of relationships between vitamin D3 metabolites and calcium-binding protein in the eggshell gland of laying birds.

    Science.gov (United States)

    Bar, A; Rosenberg, J; Hurwitz, S

    1984-01-01

    The relationship of the metabolism of vitamin D3 and calcium-binding protein (CaBP) to calcium transport by the eggshell gland (ESG) was assessed in chickens. Plasma or ESG 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) and ESG CaBP were no different between periods of ESG inactivity and of shell calcification. A severe dietary calcium deficiency resulted in increased kidney 25-hydroxycholecalciferol-1-hydroxylase activity (542%), plasma and ESG 1,25(OH)2D3 concentrations (193 and 274%, respectively), but in decreased ESG CaBP (34%), associated with the production of poorly calcified eggs. Significant correlations were found between 25 hydroxycholecalciferol-1-hydroxylase, plasma 1,25(OH)2D3 and ESG 1,25(OH)2D3, but not between ESG 1,25(OH)2D3 and CaBP. Hens with a low shell density had a significantly lower (55%) ESG CaBP than those with high shell density, without any significant change in ESG 1,25(OH)2D3. Significant correlations were found between ESG CaBP and shell calcium. Total receptors for 1,25(OH)2D3 were lower in ESG than in the intestine. The results suggest that CaBP level and calcium transport in the ESG are not regulated by 1,25(OH)2D3.

  7. Vitamin D3 protects against prednisolone-induced liver injury associated with the impairment of the hepatic NF-κB/iNOS/NO pathway.

    Science.gov (United States)

    Lisakovska, Olha; Shymanskyy, Ihor; Mazanova, Anna; Khomenko, Anna; Veliky, Mykola

    2017-04-01

    The study was carried out to define whether prednisolone-induced damage to hepatic cells is accompanied by excessive nitric oxide (NO) levels associated with nuclear factor kappa B (NF-κB)/inducible NO synthase (iNOS) activation and evaluate the efficacy of the treatment with vitamin D3. Histopathological examination, activities of liver transaminases (alanine aminotransferase and aspartate aminotransferase), and cell death assays consistently showed that prednisolone (5 mg/kg body weight, 30 days) induces chronic liver injury in female Wistar rats. Specifically, increased hepatocellular necrosis and caspase-3-dependent apoptosis were observed. Prednisolone enhanced iNOS protein expression, NO generation, and tyrosine nitration in liver cells. Despite unchanged hepatic level of the NF-κB/p65 protein, prednisolone increased inhibitory κB-α (IκB-α) degradation, nuclear translocation, and phosphorylation of NF-κB/p65 at Ser311, indicating that NF-κB activation can be involved in the induction of iNOS/NO. All changes were associated with a 2.9-fold decrease in the serum content of 25-hydroxyvitamin D3 and significant reduction of hepatic vitamin D3 receptor (VDR) expression that points reliably to vitamin D3 deficiency and failures in VDR signaling. Vitamin D3 co-administration (100 IU/rat, 30 days) prevented glucocorticoid-evoked abnormalities in hepatic tissue. In conclusion, prednisolone-induced liver disturbances were associated with the impairment of NF-κB/iNOS/NO responses that can be ameliorated by vitamin D3 treatment through VDR-mediated mechanisms.

  8. Vitamin D3 supplementation increases spine bone mineral density in adolescents and young adults with HIV infection being treated with tenofovir disoproxil fumarate: a randomized, placebo controlled trial

    Science.gov (United States)

    Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized vitamin D3 (VITD3) would increase BMD in adolescents/young adults receiving TDF. Methods: Randomized double-blind placebo-controlled trial of directly observed VITD3 50,000 IU vs. placebo every 4 ...

  9. The vitamin D analogue ED71 but Not 1,25(OH2D3 targets HIF1α protein in osteoclasts.

    Directory of Open Access Journals (Sweden)

    Yuiko Sato

    Full Text Available Although both an active form of the vitamin D metabolite, 1,25(OH2D3, and the vitamin D analogue, ED71 have been used to treat osteoporosis, anti-bone resorbing activity is reportedly seen only in ED71- but not in 1,25(OH2D3 -treated patients. In addition, how ED71 inhibits osteoclast activity in patients has not been fully characterized. Recently, HIF1α expression in osteoclasts was demonstrated to be required for development of post-menopausal osteoporosis. Here we show that ED71 but not 1,25(OH2D3, suppress HIF1α protein expression in osteoclasts in vitro. We found that 1,25(OH2D3 or ED71 function in osteoclasts requires the vitamin D receptor (VDR. ED71 was significantly less effective in inhibiting M-CSF and RANKL-stimulated osteoclastogenesis than was 1,25(OH2D3 in vitro. Downregulation of c-Fos protein and induction of Ifnβ mRNA in osteoclasts, both of which reportedly block osteoclastogenesis induced by 1,25(OH2D3 in vitro, were both significantly higher following treatment with 1,25(OH2D3 than with ED71. Thus, suppression of HIF1α protein activity in osteoclasts in vitro, which is more efficiently achieved by ED71 rather than by 1,25(OH2D3, could be a reliable read-out in either developing or screening reagents targeting osteoporosis.

  10. Effect of vitamin D3 on bone turnover markers in critical illness: post hoc analysis from the VITdAL-ICU study.

    Science.gov (United States)

    Schwetz, V; Schnedl, C; Urbanic-Purkart, T; Trummer, C; Dimai, H P; Fahrleitner-Pammer, A; Putz-Bankuti, C; Christopher, K B; Obermayer-Pietsch, B; Pieber, T R; Dobnig, H; Amrein, K

    2017-12-01

    In this post hoc analysis of the VITdAL-ICU study, an RCT in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml, vitamin D3 did not have a significant effect on β-Crosslaps and osteocalcin. Observational studies have shown accelerated bone loss in ICU survivors. A reversible contributor is vitamin D deficiency. In a post hoc analysis of the VITdAL-ICU study, we evaluated the effect of high-dose vitamin D3 on the bone turnover markers (BTM) β-Crosslaps (CTX) and osteocalcin (OC). The VITdAL-ICU study was a randomized, double-blind, placebo-controlled trial in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml who received placebo or high-dose vitamin D3 (a loading dose of 540,000 IU and starting 1 month after the loading dose five monthly maintenance doses of 90,000 IU). In this analysis on 289 survivors (209 telephone, 80 personal follow-up visits), BTM were analyzed on days 0, 3, 7, 28, and 180; self-reported falls and fractures were assessed. Bone mineral density (BMD) was measured after 6 months. At baseline, CTX was elevated; OC was low in both groups-after 6 months, both had returned to normal. There were no differences between groups concerning BTM, BMD, falls, or fractures. In linear mixed effects models, CTX and OC showed a significant change over time (p < 0.001, respectively), but there was no difference between the vitamin D and placebo group (p = 0.688 and p = 0.972, respectively). Vitamin D supplementation did not have a significant effect on BTM. Further studies should assess the effectiveness of vitamin D on musculoskeletal outcomes in ICU survivors.

  11. Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial.

    Science.gov (United States)

    Martineau, Adrian R; James, Wai Yee; Hooper, Richard L; Barnes, Neil C; Jolliffe, David A; Greiller, Claire L; Islam, Kamrul; McLaughlin, David; Bhowmik, Angshu; Timms, Peter M; Rajakulasingam, Raj K; Rowe, Marion; Venton, Timothy R; Choudhury, Aklak B; Simcock, David E; Wilks, Mark; Degun, Amarjeet; Sadique, Zia; Monteiro, William R; Corrigan, Christopher J; Hawrylowicz, Catherine M; Griffiths, Christopher J

    2015-02-01

    Patients with chronic obstructive pulmonary disease (COPD) often have vitamin D deficiency, which is associated with increased susceptibility to upper respiratory infection-a major precipitant of exacerbation. Multicentre trials of vitamin D supplementation for prevention of exacerbation and upper respiratory infection in patients with COPD are lacking. We therefore investigated whether vitamin D3 (colecalciferol) supplementation would reduce the incidence of moderate or severe COPD exacerbations and upper respiratory infections. We did a randomised, double-blind, placebo-controlled trial of vitamin D3 supplementation in adults with COPD in 60 general practices and four Acute National Health Service Trust clinics in London, UK. Patients were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 or placebo over 1 year in a 1:1 ratio using computer-generated permuted block randomisation. Participants and study staff were masked to treatment assignment. Coprimary outcomes were time to first moderate or severe exacerbation and first upper respiratory infection. Analysis was by intention to treat. A prespecified subgroup analysis was done to assess whether effects of the intervention on the coprimary outcomes were modified by baseline vitamin D status. This trial is registered with ClinicalTrials.gov, number NCT00977873. 240 patients were randomly allocated to the vitamin D3 group (n=122) and placebo group (n=118). Vitamin D3 compared with placebo did not affect time to first moderate or severe exacerbation (adjusted hazard ratio 0·86, 95% CI 0·60-1·24, p=0·42) or time to first upper respiratory infection (0·95, 0·69-1·31, p=0·75). Prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L (0·57, 0·35-0·92, p=0·021), but not in those with baseline 25-hydroxyvitamin D levels of at least 50 nmol/L (1·45, 0

  12. Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of β-catenin signaling

    Science.gov (United States)

    Pálmer, Héctor G.; González-Sancho, José Manuel; Espada, Jesús; Berciano, María T.; Puig, Isabel; Baulida, Josep; Quintanilla, Miguel; Cano, Amparo; de Herreros, Antonio García; Lafarga, Miguel; Muñoz, Alberto

    2001-01-01

    The β-catenin signaling pathway is deregulated in nearly all colon cancers. Nonhypercalcemic vitamin D3 (1α,25-dehydroxyvitamin D3) analogues are candidate drugs to treat this neoplasia. We show that these compounds promote the differentiation of human colon carcinoma SW480 cells expressing vitamin D receptors (VDRs) (SW480-ADH) but not that of a malignant subline (SW480-R) or metastasic derivative (SW620) cells lacking VDR. 1α,25(OH)2D3 induced the expression of E-cadherin and other adhesion proteins (occludin, Zonula occludens [ZO]-1, ZO-2, vinculin) and promoted the translocation of β-catenin, plakoglobin, and ZO-1 from the nucleus to the plasma membrane. Ligand-activated VDR competed with T cell transcription factor (TCF)-4 for β-catenin binding. Accordingly, 1α,25(OH)2D3 repressed β-catenin–TCF-4 transcriptional activity. Moreover, VDR activity was enhanced by ectopic β-catenin and reduced by TCF-4. Also, 1α,25(OH)2D3 inhibited expression of β-catenin–TCF-4-responsive genes, c-myc, peroxisome proliferator-activated receptor δ, Tcf-1, and CD44, whereas it induced expression of ZO-1. Our results show that 1α,25(OH)2D3 induces E-cadherin and modulates β-catenin–TCF-4 target genes in a manner opposite to that of β-catenin, promoting the differentiation of colon carcinoma cells. PMID:11470825

  13. A Randomized Double-Blind Placebo-Controlled Trial of the Effect of Vitamin D3 Supplementation on Breast Density in Premenopausal Women.

    Science.gov (United States)

    Brisson, Jacques; Bérubé, Sylvie; Diorio, Caroline; Mâsse, Benoît; Lemieux, Julie; Duchesne, Thierry; Delvin, Edgar; Vieth, Reinhold; Yaffe, Martin J; Chiquette, Jocelyne

    2017-08-01

    Background: This double-blind, placebo-controlled parallel group trial assessed whether oral supplementation with 1,000, 2,000, or 3,000 IU/day vitamin D3 over one year reduces percent mammographic breast density in premenopausal women.Methods: The trial was conducted between October 2012 and June 2015, among premenopausal female volunteers from Quebec City (Quebec, Canada). Women were randomized with ratio 1:1:1:1 to one of four study arms (1,000, 2,000, or 3,000 IU/day vitamin D3 or placebo). The primary outcome was mean change in percent mammographic breast density. Participants and research team were blinded to study arm assignment.Results: Participants (n = 405) were randomized to receive 1,000 (n = 101), 2,000 (n = 104), or 3,000 IU/day (n = 101) vitamin D3, or a placebo (n = 99). The primary analysis included 391 participants (96, 99, 100, and 96, respectively). After the one-year intervention, mean ± SE change in percent breast density in the arms 1,000 IU/day (-5.5% ± 0.5%) and 2,000 IU/day (-5.9% ± 0.5%) vitamin D3 was similar to that in the placebo arm (-5.7% ± 0.5%) (P values = 1.0). In the 3,000 IU/day vitamin D3 arm, percent breast density also declined but slightly less (-3.8% ± 0.5%) compared with placebo arm (P = 0.03). Adherence to intervention was excellent (92.8%), and reporting of health problems was comparable among study arms (P ≥ 0.95). All participants had normal serum calcium.Conclusions: In premenopausal women, one-year supplementation with 1,000, 2,000, or 3,000 IU/day vitamin D3 resulted in a reduction of percent breast density no greater than that seen with the placebo.Impact: At doses of 1,000-3,000 IU/day, vitamin D supplementation will not reduce breast cancer risk through changes in breast density. Cancer Epidemiol Biomarkers Prev; 26(8); 1233-41. ©2017 AACR. ©2017 American Association for Cancer Research.

  14. Amelioration of altered oxidant/antioxidant balance of Indian water buffaloes with subclinical mastitis by vitamins A, D3, E, and H supplementation.

    Science.gov (United States)

    Dimri, Umesh; Sharma, Mahesh Chandra; Singh, Shanker K; Kumar, Pankaj; Jhambh, Ricky; Singh, Bishwambhar; Bandhyopadhyay, Samiran; Verma, Med Ram

    2013-04-01

    The effect of vitamins A, D3, E, and H supplementation on oxidative stress indices in Indian water buffaloes suffering from subclinical mastitis was investigated. Changes in the total oxidant capacity (TOC), total antioxidant capacity (TAC), nitric oxide (NO), and activities of glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) in milk were evaluated before and after the supplementation of vitamins A, D3, E, and H. The buffaloes suffering from subclinical mastitis revealed remarkable alterations in the milk oxidants/antioxidants balance shifted towards oxidative status. The buffaloes with subclinical mastitis revealed significantly (P ≤ 0.01) higher TOC, NO contents, and CAT activity, while TAC content and GSH-Px activity were significantly (P ≤ 0.01) lower in comparison with the healthy controls. However, SOD activity did not show any significant change. Supplementation of vitamins A, D3, E, and H to these animals revealed significant (P ≤ 0.01) reduction in TOC, NO, and CAT, while a significant (P ≤ 0.01) increase in TAC and GSH-Px activity was also evident. From the present study, it may be concluded that supplementation of these vitamins can help ameliorate the altered milk oxidants/antioxidants balance towards normalcy and, thus, ensue recovery from subclinical mastitis in the Indian water buffaloes.

  15. Vitamin D3 supplementation increases insulin level by regulating altered IP3 and AMPA receptor expression in the pancreatic islets of streptozotocin-induced diabetic rat.

    Science.gov (United States)

    Jayanarayanan, Sadanandan; Anju, Thoppil R; Smijin, Soman; Paulose, Cheramadathikudiyil Skaria

    2015-10-01

    Pancreatic islets, particularly insulin-secreting β cells, share common characteristics with neurons. Glutamate is one of the major excitatory neurotransmitter in the brain and pancreas, and its action is mediated through glutamate receptors. In the present work, we analysed the role of vitamin D3 in the modulation of AMPA receptor subunit and their functional role in insulin release. Radio receptor binding study in diabetic rats showed a significant increase in AMPA receptor density. Insulin AMPA colabelling study showed an altered AMPA GluR2 and GluR4 subunit expression in the pancreatic beta cells. We also found lowered IP3 content and decreased IP3 receptor in pancreas of diabetic rats. The alterations in AMPA and IP3 receptor resulted in reduced cytosolic calcium level concentration, which further blocks Ca(2+)-mediated insulin release. Vitamin D3 supplementation restored the alteration in vitamin D receptor expression, AMPA receptor density and AMPA and IP3 receptor expression in the pancreatic islets that helps to restore the calcium-mediated insulin secretion. Our study reveals the antidiabetic property of vitamin D3 that is suggested to have therapeutic role through regulating glutamatergic function in diabetic rats. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Nasal Levels of Antimicrobial Peptides in Allergic Asthma Patients and Healthy Controls: Differences and Effect of a Short 1,25(OH2 Vitamin D3 Treatment.

    Directory of Open Access Journals (Sweden)

    Willemien Thijs

    Full Text Available Allergy is often accompanied by infections and lower levels of antimicrobial peptides (AMPs. Vitamin D has been shown to increase expression of selected AMPs. In this study we investigated whether antimicrobial peptide levels in nasal secretions of allergic asthma patients are lower than in healthy controls, and whether administration of the active form of vitamin D (1,25(OH2D3 affects these antimicrobial peptide levels.The levels of antimicrobial peptides in nasal secretions were compared between 19 allergic asthma patients and 23 healthy controls. The effect of seven days daily oral treatment with 2 μg 1,25(OH2D3 on antimicrobial peptides in nasal secretions was assessed in a placebo-controlled cross-over clinical study.Levels of neutrophil α-defensins (human neutrophil peptides 1-3; HNP1-3 and lipocalin 2 (LCN2; also known as NGAL were significantly lower in asthmatics, but no differences in LL-37 and SLPI were detected. Treatment with a short-term 1,25(OH2D3 caused a small increase in HNP1-3, but not when the asthma and control groups were analyzed separately. LL-37, LCN2 and SLPI did not change after treatment with 1,25(OH2D3.Levels of the antimicrobial peptides HNP1-3 and LCN2 are lower in nasal secretions in asthmatics and are not substantially affected by a short-term treatment with active vitamin D.

  17. Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Rolf, Linda; Muris, Anne-Hilde; Mathias, Amandine; Du Pasquier, Renaud; Koneczny, Inga; Disanto, Giulio; Kuhle, Jens; Ramagopalan, Sreeram; Damoiseaux, Jan; Smolders, Joost; Hupperts, Raymond

    2017-07-01

    Epstein-Barr virus (EBV) infection and vitamin D insufficiency are potentially interacting risk factors for multiple sclerosis (MS). To investigate the effect of high-dose vitamin D3 supplements on antibody levels against the EBV nuclear antigen-1 (EBNA-1) in patients with relapsing-remitting multiple sclerosis (RRMS) and to explore any underlying mechanism affecting anti-EBNA-1 antibody levels. This study utilized blood samples from a randomized controlled trial in RRMS patients receiving either vitamin D3 (14,000 IU/day; n = 30) or placebo ( n = 23) over 48 weeks. Circulating levels of 25-hydroxyvitamin-D, and anti-EBNA-1, anti-EBV viral capsid antigen (VCA), and anti-cytomegalovirus (CMV) antibodies were measured. EBV load in leukocytes, EBV-specific cytotoxic T-cell responses, and anti-EBNA-1 antibody production in vitro were also explored. The median antibody levels against EBNA-1, but not VCA and CMV, significantly reduced in the vitamin D3 group (526 (368-1683) to 455 (380-1148) U/mL) compared to the placebo group (432 (351-1280) to 429 (297-1290) U/mL; p = 0.023). EBV load and cytotoxic T-cell responses were unaffected. Anti-EBNA-1 antibody levels remained below detection limits in B-cell cultures. High-dose vitamin D3 supplementation selectively reduces anti-EBNA-1 antibody levels in RRMS patients. Our exploratory studies do not implicate a promoted immune response against EBV as the underlying mechanism.

  18. The Associations of Novel Vitamin D3 Metabolic Gene CYP27A1 Polymorphism, Adiponectin/Leptin Ratio, and Metabolic Syndrome in Middle-Aged Taiwanese Males

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    Kai-Hung Cheng

    2015-01-01

    Full Text Available 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.

  19. A Randomised, Double-Blind, Placebo-Controlled Trial with Vitamin D3 in MS: Subgroup Analysis of Patients with Baseline Disease Activity Despite Interferon Treatment

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    J. Åivo

    2012-01-01

    Full Text Available We present a subgroup analysis of the first double-blind, placebo-controlled, randomised trial with vitamin D3 in MS. In the overall study population, there were 34 patients in the vitamin D arm and 32 patients in the placebo arm. All the patients were using interferon-β-1b (IFNB therapy. The subgroup consisted of 15 patients in the vitamin D arm and 15 patients in the placebo arm, who had either at least one relapse during the year preceding the study or enhancing T1 lesions at the baseline MRI scan. We measured the total number of MRI T1 enhancing lesions, the number of new/enlarging T2 lesions and T2 lesion volume (BOD (mm3, EDSS (Expanded Disability Status Scale, annual relapse Rate (ARR, timed 25-foot walk (T25FW, and timed 10-foot tandem walk (TT10W at baseline and at 12 months in the vitamin D-treated and in the placebo-treated patients. There was a statistically significant reduction in the number of T1 enhancing lesions, a smaller T2 lesion volume growth and less new/enlarging T2 brain MRI lesions in the vitamin D3-treated than in the placebo-treated subgroup patients. The MRI results were slightly more pronounced in the subgroup than in the overall study population.

  20. Efficacy of High-Dose Supplementation With Oral Vitamin D3 on Depressive Symptoms in Dialysis Patients With Vitamin D3 Insufficiency: A Prospective, Randomized, Double-Blind Study.

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    Wang, Ying; Liu, Ying; Lian, Yueying; Li, Ning; Liu, Hong; Li, Guanzeng

    2016-06-01

    Psychological problems are common among end-stage renal disease patients undergoing dialysis. We aim to evaluate whether high-dose vitamin D3 (VD3) supplementation has beneficial effects on depressive symptoms in dialysis patients. This prospective, randomized, and double-blind trial includes 746 dialysis patients with depression treated in 3 hospitals in Southeast China. Depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders criteria. Patients were randomly assigned to 52-week treatment of oral 50,000 IU/wk VD3 (cholecalciferol) (test group) or a placebo (control group). The presence of depressive symptoms was evaluated using the Chinese version of Beck Depression Inventory (BDI) II both before and after treatment. Sociodemographic data, clinical data, nutritional indexes, inflammatory biomarkers, and plasma VD3 concentrations were also determined. Finally, 726 patients completed the experiments, including 362 tested patients and 364 controls. After 52 weeks, the depressive symptoms were not significantly improved in the test group (mean BDI II scores changed from -1.1 ± 0.3 to -3.1 ± 0.6) versus the control group. Multivariable logistic regression showed BDI scores were not significantly improved in the test group versus the control group with adjustment for age, sex, comorbidity index, dialysis modality, or (OH)D levels (multivariable-adjusted mean change or MAMC [95% confidence interval (CI)], -2.3 [-2.48 to -1.83]) in the whole dialysis population. After stratification by depression types, the findings do support a significant relationship between the VD3 supplementation and the improvement in BDI II scores in dialysis patients with vascular depression (MAMC [95% CI], -4.4 [-5.08 to -2.76]), but the effect was not significant for major depressive disorders (MAMC [95% CI], -0.9 [-1.52 to -0.63]). The high-dose VD3 supplementation did not significantly reduce the depressive symptoms in our total dialysis population, but

  1. 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.

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    Weiss, W P; Azem, E; Steinberg, W; Reinhardt, T A

    2015-08-01

    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 (16 cows) was formulated to provide 18,000 IU/d of vitamin D3 and had a dietary cation-anion difference (DCAD) of 165mEq/kg (DCAD=Na + K - Cl - S). The second diet (DCAD + D) provided the same amount of vitamin D3 but had a DCAD of -139mEq/kg (17 cows). The third diet (DCAD + 25D) had no supplemental vitamin D3 but provided 6mg/d of 25-(OH) vitamin D3 [25-(OH)D3] with a DCAD of -138mEq/kg (20 cows). Diets were fed until parturition and then all cows were fed a common lactation diet that contained vitamin D3. Negative DCAD diets reduced urine pH, with the greatest decrease occurring with the DCAD + D treatment. Urinary Ca excretion was greatest for cows fed DCAD + 25D followed by cows fed DCAD + D. Urinary pH was negatively correlated with urinary excretion of Ca for cows fed DCAD + D. No such correlation was observed with the DCAD + 25D treatment because substantial excretion of urinary Ca occurred at moderate urinary pH values for that treatment. Cows fed DCAD + 25D had greater serum concentrations of 25-(OH)D3 than other treatments from 5 d after supplementation started through 7 d in milk. Concentrations of 1,25-(OH)2D3 in serum were greatest in DCAD + 25D cows starting at 2 d before calving and continued through 7 d in milk. Serum Ca concentrations 5 d before calving were greatest for cows fed DCAD + 25D, but at other time points before and after parturition treatment did not affect serum Ca. Incidence of clinical hypocalcemia was not statistically different between treatments, but cows fed DCAD + 25 had the highest incidence rate (12.5, 0, and 20% for control, DCAD + D, and DCAD + 25D). Calves born from cows fed DCAD + 25D had greater concentrations of 25-(OH)D3 in serum at birth than calves from other treatments (before colostrum consumption), but concentrations were similar by 3 d of age. Concentrations of 25-(OH)D3 in colostrum and

  2. Effect of Vitamin D3 Supplementation on Respiratory Tract Infections in Healthy Individuals: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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    Vuichard Gysin, Danielle; Dao, Dyda; Gysin, Christian Michael; Lytvyn, Lyubov; Loeb, Mark

    2016-01-01

    Vitamin D supplementation may be a simple preventive measure against respiratory tract infections (RTIs) but evidence from randomized controlled trials is inconclusive. We aimed to systematically summarize results from interventions studying the protective effect of vitamin D supplementation on clinical and laboratory confirmed RTIs in healthy adults and children. Medline, EMBASE, CENTRAL, and CINAHL were screened from inception until present (last updated in January 2016) completed by a search of the grey literature, clinical trial registers and conference abstracts. We included randomized trials comparing vitamin D versus placebo or no treatment. Two independent reviewers were responsible for study selection and data extraction. Cochrane's risk of bias tool and the GRADE approach were used for quality assessment. Estimates were pooled with random-effects models. Heterogeneity was explored by sub-group and meta-regression analyses. Of 2627 original hits, 15 trials including 7053 individuals were ultimately eligible. All used oral cholecalciferol. We found a 6% risk reduction with vitamin D3 supplementation on clinical RTIs, but the result was not statistically significant (RR 0.94; 95% CI 0.88 to 1.00). Heterogeneity was large (I-square 57%) and overall study quality was low. There were too few studies to reliably assess a potential risk reduction of laboratory confirmed RTI. Evidence was insufficient to demonstrate an association between vitamin D supplementation and risk of clinical RTI in sub-groups with vitamin D deficiency. In previously healthy individuals vitamin D supplementation does not reduce the risk of clinical RTIs. However, this conclusion is based on a meta-analysis where the included studies differed with respect to population, baseline vitamin D levels and study length. This needs to be considered when interpreting the results. Future trials should focus on vitamin D deficient individuals and apply more objective and standardized outcome

  3. Levels of 25(OHD3, IL-2, and C-peptide in Children with Type 1 Diabetes Mellitus (T1DM Receiving Vitamin D3 Supplementation

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    Tjahyo Suryanto

    2018-01-01

    Full Text Available Type 1 Diabetes Mellitus (T1DM has become a health problem in many countries. T1DM is the consequence of autoimmune destruction process of β cells. There was relationship between vitamin D deficiency with T1DM. The destruction process was caused by an imbalance of pro-inflammatory and anti-inflammatory cytokines. One of the pro-inflammatory cytokines is IL-2. C-peptide examination to see the function of beta cells due to destruction of pancreatic beta cell. Administration of vitamin D3 supplementation still cause controversy and give varying results. This randomized clinical trial was conducted to determine the levels of 25(OHD3, IL-2, and C-peptide in people with T1DM who received vitamin D3 supplementation. The subjects were 26 children with T1DM, divided into K1 group (received vitamin D3 supplementation and K2 group (received placebo. The results showed higher levels of 25(OHD3 in the K1 group and statistically found a significant difference (p = 0.00. Higher levels of IL-2 and lower C-peptide were obtained in the K1 group and no statistically significant differences were found (p = 0.76 and p= 0.26. The insignificant relationship and the negative correlation were found between 25(OHD3 and IL-2 (p = 0.71; r = - 0.12, 25(OHD3 and C-peptide (p = 0.59; r = -0.16, also levels of IL-2 and C-peptide (p = 0.13; r = -0.44 in children with type 1 diabetes who received vitamin D3 supplementation. From this study can be concluded that administration vitamin D3 supplementation in patients with T1DM can increase levels 25(OHD3 significantly. This increase has not significantly lowered levels of IL-2 and increased levels of C-peptide. However, there was an absolute decrease in the rate of slower C-peptide in the supplemented group than in the placebo group.

  4. Effects of the Administration of 25(OH) Vitamin D3 in an Experimental Model of Chronic Kidney Disease in Animals Null for 1-Alpha-Hydroxylase.

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    Torremadé, Noelia; Bozic, Milica; Goltzman, David; Fernandez, Elvira; Valdivielso, José M

    2017-01-01

    The final step in vitamin D activation is catalyzed by 1-alpha-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is characterized by low levels of both 25(OH)D3 and 1,25(OH)2D3 provoking secondary hyperparathyroidism (2HPT). Therefore, treatments with active or native vitamin D compounds are common in CKD to restore 25(OH)D3 levels and also to decrease PTH. This study evaluates the dose of 25(OH)D3 that restores parathyroid hormone (PTH) and calcium levels in a model of CKD in CYP27B1-/- mice. Furthermore, we compare the safety and efficacy of the same dose in CYP27B1+/+ animals. The dose needed to decrease PTH levels in CYP27B1-/- mice with CKD was 50 ng/g. That dose restored blood calcium levels without modifying phosphate levels, and increased the expression of genes responsible for calcium absorption (TRPV5 and calbindinD- 28K in the kidney, TRPV6 and calbindinD-9k in the intestine). The same dose of 25(OH)D3 did not modify PTH in CYP27B1+/+ animals with CKD. Blood calcium remained normal, while phosphate increased significantly. Blood levels of 25(OH)D3 in CYP27B1-/- mice were extremely high compared to those in CYP27B1+/+ animals. CYP27B1+/+ animals with CKD showed increases in TRPV5, TRPV6, calbindinD-28K and calbindinD-9K, which were not further elevated with the treatment. Furthermore, CYP27B1+/+ animals displayed an increase in vascular calcification. We conclude that the dose of 25(OH)D3 effective in decreasing PTH levels in CYP27B1-/- mice with CKD, has a potentially toxic effect in CYP27B1+/+ animals with CKD.

  5. 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

    Science.gov (United States)

    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...

  6. Bioequivalence of Alendronate and Vitamin D3 in a Combination Tablet Versus Corresponding-Dose Individual Tablets in Healthy Taiwanese Volunteers, Determined Using a Novel Plasma Alendronate Assay

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    D. Hamish Wright, PhD

    2015-12-01

    Conclusions: The combination tablet was considered bioequivalent to coadministration based on ALN AUC0–∞ and unadjusted vitamin D3 parameters. Slight differences for ALN AUC0–last and Cmax (upper 90% CIs outside the bounds were not considered clinically significant. The combination tablet was well tolerated. No serious adverse experiences were reported. © 2015. The Authors. Published by Elsevier Inc. All rights reserved.

  7. Eldecalcitol, an Active Vitamin D3Derivative, Prevents Trabecular Bone Loss and Bone Fragility in Type I Diabetic Model Rats.

    Science.gov (United States)

    Takeda, Satoshi; Saito, Mitsuru; Sakai, Sadaoki; Yogo, Kenji; Marumo, Keishi; Endo, Koichi

    2017-10-01

    Diabetes mellitus is known to adversely affect the bones and be associated with increased fracture risk. We examined whether eldecalcitol (ELD), an active vitamin D 3 derivative, could inhibit the diabetic bone loss in streptozotocin-induced type I diabetic rats. ELD (10, 20, or 40 ng/kg), alfacalcidol (ALF; 25, 50, or 100 ng/kg), or vehicle was administered 5 times per week for 12 weeks from 1 week after diabetes induction. Normal control rats received the vehicle. Bone turnover markers, bone mineral density (BMD), and biomechanical strength of the lumbar spine and femur were measured, and bone histomorphometry was performed. Content of advanced glycation end products (AGEs) in the femoral shaft was also determined. In diabetic rats, serum osteocalcin (OC) concentration was lower and urinary excretion of deoxypyridinoline (DPD) tended to be higher than in normal rats. Areal BMD and maximum load of the lumbar vertebrae and femoral shaft were lower in diabetic rats than in normal rats. All doses of ELD and the highest dose of ALF reduced urinary DPD excretion, but had no effect on serum OC. The 20 and 40 ng/kg doses of ELD prevented decreases in BMD and the highest dose of ELD prevented the reduction in maximum load of the lumbar vertebrae, while ALF did not change these parameters. ELD and ALF did not affect areal BMD or biomechanical strength of the femoral shaft. In diabetic rats, bone volume and trabecular thickness in the trabecular bone of the lumbar vertebrae decreased and trabecular separation increased compared to normal rats. ELD and ALF prevented diabetes-induced deterioration of trabecular microstructure. AGE content in the femoral cortical bone increased in the diabetic rats, and ELD and ALF did not change AGE content compared to the diabetic rats. These results indicated that ELD suppressed bone resorption and prevented trabecular bone loss and deterioration of trabecular microstructure, resulting in prevention of reduction in biomechanical

  8. Associations of Genetic Polymorphisms Relevant to Metabolic Pathway of Vitamin D3 with Development and Prognosis of Childhood Bronchial Asthma.

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    Zhang, Ying; Wang, Zhansheng; Ma, Tongshuai

    2017-08-01

    This study was aimed at investigating the correlation between genetic polymorphisms relevant to metabolic pathway of vitamin D3 (VD3) and susceptibility to childhood bronchial asthma. Altogether 143 childhood patients with bronchial asthma and 143 healthy children of Chinese Han ethnicity were enrolled in this study. The key single-nucleotide polymorphisms (SNPs) were identified by HaploView 4.2 software and selected from previous investigations. Genomic DNAs were isolated from peripheral blood samples by using TaqMan Blood DNA kits. The genotyping of SNPs was performed by TaqMan SNPs genotyping assay. Odds ratios and corresponding 95% confidence intervals were calculated to evaluate the association between SNPs and susceptibility to bronchial asthma. Statistical analyses were conducted by using SPSS 13.0 software. Rs10766197 of CYP2R1, rs7041 and rs4588 of CG, rs4646536 of CYP27B1, rs2228570, rs7975232, and rs1544410 of VDR, as well as rs1805192 and rs10865710 of PPAR were shown to be significantly associated with increased risk of bronchial asthma. Besides, prognosis of childhood bronchial asthma, which was represented as Saint George Respiratory Questionnaire (SGRQ) scoring, was closely linked with CYP2R1 rs10766197, CYP27B1 rs4646536, VDR rs7975232, VDR rs1544410, PPAR rs1805192, and PPAR rs10865710. The haplotype analysis suggested that TA and CG of CG rs7041/rs4588, CA and AG of VDR rs7975232/rs1544410, and CC of PPAR rs1805192/rs10865710 were, respectively, correlated with levels of VD, IL-4, and IL-5. And only haplotypes of VDR showed associations with risk of bronchial asthma during childhood, whereas hardly any significance could be observed between the haplotypes and behavior of quality-of-life (SGRQ) scoring. Significant associations were found between rs10766197 of CYP2R1, rs7041 and rs4588 of CG, rs4646536 of CYP27B1, rs2228570, rs7975232, and rs1544410 of VDR, as well as rs1805192 and rs10865710 of PPAR and susceptibility to and prognosis of

  9. 300,000 IU or 600,000 IU of oral vitamin D3 for treatment of nutritional rickets: a randomized controlled trial.

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    Mittal, Hema; Rai, Sunita; Shah, Dheeraj; Madhu, S V; Mehrotra, Gopesh; Malhotra, Rajeev Kumar; Gupta, Piyush

    2014-04-01

    To evaluate the non-inferiority of a lower therapeutic dose (300,000 IU) in comparison to standard dose (600,000) IU of Vitamin D for increasing serum 25(OH) D levels and achieving radiological recovery in nutritional rickets. Randomized, open-labeled, controlled trial. Tertiary care hospital. 76 children (median age 12 mo) with clinical and radiologically confirmed rickets. Oral vitamin D3 as 300,000 IU (Group 1; n=38) or 600,000 IU (Group 2; n=38) in a single day. Primary: Serum 25(OH)D, 12 weeks after administration of vitamin D3; Secondary: Radiological healing and serum parathormone at 12 weeks; and clinical and biochemical adverse effects. Serum 25(OH)D levels [geometric mean (95% CI)] increased significantly from baseline to 12 weeks after therapy in both the groups [Group 1: 7.58 (5.50–10.44) to 16.06 (12.71– 20.29) ng/mL, Pchildren by 12 weeks. Both groups demonstrated significant (Pchildren after 12 weeks of intervention [Group 1: 20/32 (62.5%); Group 2: 18/28 (64.3%)]. No major clinical adverse effects were noticed in any of the children. Hypercalcemia was documented in 2 children at 4 weeks (1 in each Group) and 3 children at 12 weeks (1 in Group 1 and 2 in Group 2). None of the participants had hypercalciuria or hypervitaminosis D. A dose of 300,000 IU of vitamin D3 is comparable to 600,000 IU, administered orally, over a single day, for treating rickets in under-five children although there is an unacceptably high risk of hypercalcemia in both groups. None of the regime is effective in normalization of vitamin D status in majority of patients, 3 months after administering the therapeutic dose.

  10. Protective Effect of Vitamin D3 and Gp63 Conjugated with Tetanus Toxoid on Outcome of Cutaneous Leishmaniasis Lesions in Balb/C Mice

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    S Soudi

    2006-01-01

    Full Text Available Introduction: GP63 is a major surface protease of Leishmania promastigotes that plays an important role in its virulance. As GP63 on its own can not develop an effective protection against leishmaniasis, the goal of this study was to evaluate the protective effect of GP63 conjugated with tetanus toxoid (TT and Vitamin D3 in susceptible BALB/c mice against cutaneous leishmaniasis. Methods: This study was a basic-applied experimental study performed in Tarbiat Modarres University from September 2002 to April 2005. Cloned virulant Leishmania (L. major [MRHO / IR / 75 / ER] strain was cultured and 5109 cells were harvested. GP63 Molecule was purified and conjugated with TT and conjugated molecule was used for immunization of 8 groups of female BALB/c mice. Results: Results showed that the group of mice receiving conjugated molecule with Vitamin D3 had significant differences from other groups regarding lesion progression (P0.05. The culture of spleen cells showed that the disease did not become systemic in this group. Conclusion: Conjugation of GP63 with TT strengthens cell immunity and its use along with vitamin D3 provokes macrophages activity. This basis can be used for production of an appropriate preparation for protection against Leishmaniasis.

  11. Effects of parenteral gibberellic acid and dietary supplementaion of vitamin D3 on egg quality and physiological characteristics in aged laying hens

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    Waleed M. Razuki

    2014-12-01

    Full Text Available The aim of this study was to determine the effect of parenteral gibberellic acid (GA3 and/or vitamin D3 supplementation in diet on egg quality and blood physiological characteristics in aged laying hens. A total of 270 Lohmann Brown Classic laying hens aging 73-week were randomly assigned to equal three treatment groups (T1, T2 and T3 with equal 3 replicas in each group. The birds of group T1 (control group were injected subcutaneously (SC with sesame oil at 0.2 mL/kg body weight. The birds of group T2 were given with GA3 at 400 µg/kg b.wt., SC, whereas group T3 had diet containing vitamin D3 at 500 IU/kg feed. Relative weight of albumen and egg shell, Haugh unit, shell thickness, serum glucose, serum calcium, serum phosphorous, serum estradiol, and bone calcium absorption were significantly increased in the birds of group T2 and T3. On the other hand, relative weight of yolk, yolk cholesterol, and serum cholesterol were significantly decreased in group T2 and T3 as compared to group T1. However, serum protein and albumen were unaffected in the treatments. In conclusion, the parenteral GA3 and vitamin D3 supplementation in diet could improve egg quality traits and serum blood biochemical perperties in agend laying hens.

  12. Comparison of vitamin D3 serum levels in new diagnosed patients with multiple sclerosis versus their healthy relatives.

    Science.gov (United States)

    Mazdeh, Mehrdokht; Seifirad, Soroush; Kazemi, Niloofar; Seifrabie, Mohammad Ali; Dehghan, Arash; Abbasi, Hamidreza

    2013-05-30

    Multiple risk factors are introduced for Multiple Sclerosis (MS). Recent studies have suggested a possible correlation between vitamin D deficiency and an increase risk of MS. This study was therefore undertaken to compare vitamin D levels in new cases of MS and their relatives as healthy controls. Seventy five new diagnosed MS patients and 100 matched healthy controls among their relatives were enrolled in this study. Two groups were matched for gender, age, season in which serum level of vitamin D was checked and region and diet. Serum levels of 25-hydroxy vitamin D was measured, recorded and analyzed. Seventy five patients (57 female and 18 male) and 100 healthy subjects (75 female and 25 male) were enrolled in this study. The mean serum levels of 25-hydroxy vitamin D in case and control groups were 11.31 and 17.9 ng/ml, respectively (P=0.003). Compared to the healthy subject, serum levels of vitamin D were significantly lower in patients with MS. This difference was only significant in women. Observed difference of vitamin D levels of both groups were significant in summer. This study continues to support the role of vitamin D deficiency in MS.

  13. Comparison of Vitamin D3 Serum Levels in New Diagnosed Patients with Multiple Sclerosis versus Their Healthy Relatives

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    Hamidreza Abbasi

    2013-05-01

    Full Text Available Multiple risk factors are introduced for Multiple Sclerosis (MS. Recent studies have suggested a possible correlation between vitamin D deficiency and an increase risk of MS. This study was therefore undertaken to compare vitamin D levels in new cases of MS and their relatives as healthy controls. Seventy five new diagnosed MS patients and 100 matched healthy controls among their relatives were enrolled in this study. Two groups were matched for gender, age, season in which serum level of vitamin D was checked and region and diet. Serum levels of 25-hydroxy vitamin D was measured, recorded and analyzed. Seventy five patients (57 female and 18 male and 100 healthy subjects (75 female and 25 male were enrolled in this study. The mean serum levels of 25-hydroxy vitamin D in case and control groups were 11.31 and 17.9 ng/ml, respectively (P=0.003. Compared to the healthy subject, serum levels of vitamin D were significantly lower in patients with MS. This difference was only significant in women. Observed difference of vitamin D levels of both groups were significant in summer. This study continues to support the role of vitamin D deficiency in MS.

  14. Vitamin D3 supplementation increases fibroblast growth factor-23 in HIV-infected youth treated with tenofovir disoproxil fumarate

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    Tenofovir (TDF) is associated with phosphaturia and elevated 1,25 dihydroxy vitamin D (1,25-OH(2)D). Fibroblast growth factor-23 causes phosphaturia and increases in response to elevated 1,25-OH(2)D. Vitamin D binding proetin (VDBP) binds to 1,25-OH(2)D, decreasing biologic activity, and is elevated...

  15. The effect of a single high dose vitamin D3 on neutrophilic airway inflammation in nonatopic asthma

    NARCIS (Netherlands)

    De Groot, J.C.; Van Roon, E.N.; Storm, H.; Bel, E.H.; Ten Brinke, A.

    2012-01-01

    Rationale: Vitamin D deficiency has been associated with asthma and increased risk of respiratory tract infections. An infectious origin in its turn, has been proposed for nonatopic asthma (Joseph Ann All Asthma Immun 2003) as well as neutrophilic asthma (Simpson Thorax 2007). Vitamin D enhances

  16. Importance of body weight and skin color in determining appropriate vitamin D3 supplement doses for children and adolescents.

    Science.gov (United States)

    Weishaar, Tom; Rajan, Sonali

    2015-02-01

    Deficiencies in vitamin D directly impact children's health and place minority and obese youth at risk for a range of health issues. The Institute of Medicine (IOM) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium has set both a recommended daily allowance (RDA) for vitamin D supplementation and a population-wide sufficiency target for the biomarker of vitamin D status, serum 25-hydroxyvitamin D (25(OH)D). However, new research suggests that the RDA is not sufficient to meet the target biomarker status for individuals who are heavy or who have dark skin. Our objective was to provide appropriate daily vitamin D supplementation levels for these individuals. Using data derived from the National Health and Nutrition Examination Survey (NHANES) and a recently published dosing formula, we calculated the required supplemental dose of vitamin D to meet the IOM target in children and adolescents. To be sure that 95% of the target population meets the IOM's population-wide biomarker target, some individuals require a daily dose of up to 2,000 international units (IUs) of supplemental vitamin D. Health professionals should work with their patients to encourage lifelong vitamin D supplement use at a dosage sufficient to obtain adequate 25(OH)D levels.

  17. Vitamin D3 Decreases Parathyroid Hormone in HIV-Infected Youth Being Treated With Tenofovir: A Randomized, Placebo-Controlled Trial

    Science.gov (United States)

    Stephensen, Charles B.; Hazra, Rohan; Flynn, Patricia M.; Wilson, Craig M.; Rutledge, Brandy; Bethel, James; Pan, Cynthia G.; Woodhouse, Leslie R.; Van Loan, Marta D.; Liu, Nancy; Lujan-Zilbermann, Jorge; Baker, Alyne; Kapogiannis, Bill G.; Mulligan, Kathleen

    2012-01-01

    Background. The study goal was to determine the effect of vitamin D (VITD) supplementation on tubular reabsorption of phosphate (TRP), parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and C-telopeptide (CTX) in youth infected with human immunodeficiency virus (HIV) receiving and not receiving combination antiretroviral therapy (cART) containing tenofovir disoproxil fumarate (TDF). Methods. This randomized, double-blind, placebo-controlled multicenter trial enrolled HIV-infected youth 18–25 years based on stable treatment with cART containing TDF (n = 118) or no TDF (noTDF; n = 85), and randomized within those groups to vitamin D3, 50 000 IU (n = 102) or placebo (n = 101), administered at 0, 4, and 8 weeks. Outcomes included change in TRP, PTH, BAP, and CTX from baseline to week 12 by TDF/noTDF; and VITD/placebo. Results. At baseline, VITD and placebo groups were similar except those on TDF had lower TRP and higher PTH and CTX. At week 12, 95% in the VITD group had sufficient serum 25-hydroxy vitamin D (25-OHD; ≥20 ng/mL), increased from 48% at baseline, without change in placebo (P vitamin D3 supplementation decreased PTH, regardless of baseline 25-OHD concentration. Clinical Trials Registration. NCT00490412. PMID:22267714

  18. Vitamin D3 deficiency differentially affects functional and disease outcomes in the G93A mouse model of amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Jesse A Solomon

    Full Text Available UNLABELLED: Amyotrophic lateral sclerosis (ALS is a neuromuscular disease characterized by motor neuron death in the central nervous system. Vitamin D supplementation increases antioxidant activity, reduces inflammation and improves motor neuron survival. We have previously demonstrated that vitamin D(3 supplementation at 10× the adequate intake improves functional outcomes in a mouse model of ALS. OBJECTIVE: To determine whether vitamin D deficiency influences functional and disease outcomes in a mouse model of ALS. METHODS: At age 25 d, 102 G93A mice (56 M, 46 F were divided into two vitamin D(3 groups: 1 adequate (AI; 1 IU D(3/g feed and 2 deficient (DEF; 0.025 IU D(3/g feed. At age 113 d, tibialis anterior (TA, quadriceps (quads and brain were harvested from 42 mice (22 M and 20 F, whereas the remaining 60 mice (34 M and 26 F were followed to endpoint. RESULTS: During disease progression, DEF mice had 25% (P=0.022 lower paw grip endurance AUC and 19% (P=0.017 lower motor performance AUC vs. AI mice. Prior to disease onset (CS 2, DEF mice had 36% (P=0.016 lower clinical score (CS vs. AI mice. DEF mice reached CS 2 six days later vs. AI mice (P=0.004, confirmed by a logrank test which revealed that DEF mice reached CS 2 at a 43% slower rate vs. AI mice (HR= .57; 95% CI: 0.38, 1.74; P=0.002. Body weight-adjusted TA (AI: r=0.662, P=0.001; DEF: r=0.622, P=0.006 and quads (AI: r=0.661, P=0.001; DEF: r=0.768; P<0.001 weights were strongly correlated with age at CS 2. CONCLUSION: Vitamin D(3 deficiency improves early disease severity and delays disease onset, but reduces performance in functional outcomes following disease onset, in the high-copy G93A mouse.

  19. D3-??????????????????????? ? ???? ?????????? ?2 ?????? ?????? ?????

    OpenAIRE

    ?????????, ????; ???????, ???????; ??????, ?????????; ?????????????, ????; ??????, ??????

    2011-01-01

    ????? ?????? ??????? ????? ????? ??????????? ?????? ?????? ????? ? ?????? ? ???????? ????? ?????????. ?????????? ???????????? ?????? ?? ?2 ?????? ?????? ????? ??????? ?? D3 ???????????????? ??????? ??????????? ?????? ????????? ????? ?????????? ??? ??? ??????????. ? ????? ????????????? ??????????? ??? ????????? ????????????? ?????????? ???? ?????????? ?????????? ????? ????????? ?????? ???????? ?? D3-????????????????? ???????.

  20. Results of daily oral dosing with up to 60,000 international units (iu) of vitamin D3 for 2 to 6 years in 3 adult males.

    Science.gov (United States)

    McCullough, Patrick; Amend, Jeffrey

    2017-10-01

    In the 1930's and 1940's, vitamin D was reported to be an effective treatment for a number of diseases, including asthma, psoriasis, rheumatoid arthritis, rickets and tuberculosis. High doses were used, 60,000 to 300,000 IU a day for asthma, and 200,000 to 600,000 IU a day for rheumatoid arthritis. Toxicity from hypercalcemia occurred after prolonged oral dosing with these supraphysiologic doses. Assays for measuring vitamin D in the blood were not available, and blood levels of vitamin D associated with hypercalcemia were unknown. A 2011 report on vitamin D toxicity showed that hypercalcemia resolved when 25-hydroxyvitamin D (25OHD) blood levels dropped below 400ng/ml in 2 patients with blood levels ranging from 645ng/ml to 1220ng/ml after accidental ingestion of massive doses of vitamin D. We now know that vitamin D is made in the skin in amounts ranging up to 25,000 IU a day with exposure to UVB radiation. There is little data on the safety and blood levels of 25OHD and calcium after prolonged daily intake of amounts of vitamin D in this range. In this report, one subject took increasing daily doses of vitamin D3 for 6 years starting in April 2009: 6500 IU for 6 months; increasing to 10,000 IU for 13 months; 20,000 IU for 24 months; 40,000 IU for 12 months; 50,000 IU for 10 months, and 60,000 IU since October 2014. 25OHD blood levels were 28, 81, 204, 216, 225, 166, and 218ng/ml. Subject 2 began 10,000 IU in Nov 2011, increased to 20,000 IU in Feb 2014, 25,000 IU in June 2014, and 30,000 IU in Oct 2014, and then decreased to 20,000 IU in June 2015. 25OHD blood levels were 96.6, 161.1 and 106.9ng/ml. He reported marked clinical improvement in his asthma. Subject 3 started on daily 10,000 IU in Sept 2013, increasing to 20,000 IU on Nov 2013. 25OHD blood levels were 31.4, 102, 164, 148, and 143ng/ml. No one developed hypercalcemia or any adverse events. The major finding of this case series is prolonged daily dosing of vitamin D3 with doses of 10,000 to 60,000 IU

  1. Patient preference and acceptability of calcium plus vitamin D3 supplementation: a randomised, open, cross-over trial

    NARCIS (Netherlands)

    den Uyl, D.; Geusens, P.P.; van Berkum, F.N.; Houben, H.H.; Jebbink, M.C.; Lems, W.F.

    2010-01-01

    Preference for a drug formulation is important in adherence to long-term medication for chronic illnesses such as osteoporosis. We investigated the preference for and acceptability of chewable tablet containing calcium and vitamin D (Calci Chew D

  2. Independent and combined effects of calcium-vitamin D3 and exercise on bone structure and strength in older men: an 18-month factorial design randomized controlled trial.

    Science.gov (United States)

    Kukuljan, Sonja; Nowson, Caryl A; Sanders, Kerrie M; Nicholson, Geoff C; Seibel, Markus J; Salmon, Jo; Daly, Robin M

    2011-04-01

    Exercise and calcium-vitamin D are independently recognized as important strategies to prevent osteoporosis, but their combined effects on bone strength and its determinants remain uncertain. To assess whether calcium-vitamin D(3) fortified milk could enhance the effects of exercise on bone strength, structure, and mineral density in middle-aged and older men. An 18-month factorial design randomized controlled trial in which 180 men aged 50-79 years were randomized to the following: exercise + fortified milk; exercise; fortified milk; or controls. Exercise consisted of progressive resistance training with weight-bearing impact activities performed 3 d/week. Men assigned to fortified milk consumed 400 ml/d of 1% fat milk containing 1000 mg/d calcium and 800 IU/d vitamin D(3). Changes in bone mineral density (BMD), bone structure, and strength at the lumbar spine (LS), proximal femur, mid-femur, and mid-tibia measured by dual energy x-ray absorptiometry and/or quantitative computed tomography. There were no exercise-by-fortified milk interactions at any skeletal site. Main effect analysis showed that exercise led to a 2.1% (95% confidence interval, 0.5-3.6) net gain in femoral neck section modulus, which was associated with an approximately 1.9% gain in areal BMD and cross-sectional area. Exercise also improved LS trabecular BMD [net gain 2.2% (95% confidence interval, 0.2-4.1)], but had no effect on mid-femur or mid-tibia BMD, structure, or strength. There were no main effects of the fortified milk at any skeletal site. A community-based multi-component exercise program successfully improved LS and femoral neck BMD and strength in healthy older men, but providing additional calcium-vitamin D(3) to these replete men did not enhance the osteogenic response.

  3. PROTECTIVE EFFECT OF VITAMIN D3 IN METHYLPREDNISOLONE ACETATE (MPA INDUCED LOSS OF BONE METABOLISM MARKERS AND BONE MINERAL DENSITY IN THE LUMBAR SPINE OF RAT

    Directory of Open Access Journals (Sweden)

    I. Ragerdi-Kashani

    2007-05-01

    Full Text Available Although some vitamins have been shown to prevent glucocorticoids induced osteoporosis in short time, the magnitude of this effect remains to be clarified. The aim of this study was to evaluate protective effect of vitamin D3 on methylprednisolone acetate (MPA induced osteoporosis in rats. Twenty-four male Sprague Dawley rats were randomly divided into four groups: Group A (n = 6, was a base line control or normal animals. Group B (n = 6, was treated only normal saline, group C (n = 6, was treated MPA (0.2 mg/kg subcutaneously for 4 weeks (3 times per a week and finally group D (n = 6 were administered MPA resemble to group C and treated by Vitamin D3 (0.1 µg/kg dissolved in ethanol daily. Level of calcium, osteocalcin and acid phosphatase in serum were measured before and after treatment. Also, bone mineral density (BMD of lumber vertebrae was measured by dual energy X-ray absorptiometry. The results showed that the serum calcium level unaffected by MPA in all groups before and after treatment, but the serum osteocalcin level and bone mineral density of lumbar vertebrae were significantly (P < 0.05 decreased in group C compared with groups A and B. In group D serum osteocalcin level increased again significantly (P < 0.05 but increasing of BMD and bone mineral content were not significant. The findings indicate that by using of vitamin D3 in MPA treated rats could increase bone formation and decrease bone resorption.

  4. Vitamin D3 levels and NLRP3 expression in murine models of obese asthma: association with asthma outcomes

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    J-H. Zhang

    2017-11-01

    Full Text Available Vitamin D (25(OHD3 is an essential nutrient that plays a role in the immune system. Serum 25(OHD3 is found to be associated with asthma. However, the role of vitamin D in obese asthma remains unclear. Therefore, we investigated the association between vitamin D levels and asthma outcomes in a murine model of obese asthma. We also evaluated NLRP3 inflammasome activity in the pathogenesis of obese asthma. We divided 20 male Balb/c mice (3–4 weeks old into 4 groups: normal control, asthma, obese, and obese asthma and developed an obese asthma mouse model. Airway hyperreactivity, cytokine concentrations, 25(OHD3 levels, NLRP3 mRNA and IL-1β mRNA expressions were measured. Lung histology and bronchoalveolar lavage fluid (BALF cell count were also determined. Obese asthma mice showed a significant increase in airway hyper-responsiveness, airway inflammation, pro-inflammatory cytokine levels and NLRP3 mRNA, IL-1β mRNA expression. Both asthma and obese groups had lower 25(OHD3 levels. Vitamin D levels in obese asthma were the lowest among all groups. Vitamin D levels correlated negatively with body weight, lung resistance levels at 25 mg/mL of methacholine, total inflammatory cells, and IL-1β and IL-17 concentrations in BALF. These data demonstrated an association between serum vitamin D levels and outcomes of obese asthma, and indicated that NLRP3 inflammasome may play a role in this disorder.

  5. Scenario for adequate cutaneous vitamin D 3 synthesis due to solar radiation in Poland for people with phototype II and III

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    Joanna Narbutt

    2016-12-01

    Full Text Available Introduction. The limited outdoor activity of contemporary people results in deficiency of vitamin D. An adequate vitamin D level cannot be achieved due to random insolation. A scenario of pro-healthy outdoor behavior is needed that takes into account climatic conditions in Poland. Objective . To present the outdoor activity scenario in Poland for people with phototype II and III to get an adequate vitamin D 3 dose without the risk of erythema. Material and methods. The paper presents the results of mathematical simulations of UV doses received by persons with phototype II and III in the spring/summer season in Poland (Jastrzębia Góra, Zakopane. The following scenarios are examined: using all the time a sunscreen with SPF30, short sunbathing without photo-protection and application of a sunscreen with SPF30 for the rest of the day. Results. During late spring and summer in Poland it is possible to get a vitamin D 3 dose of 2000 IU due to solar radiation without the risk of erythema. For persons with phototype II and III short (20–30 min near-noon exposure without photo-protection then application of sunscreen with SPF30 for the rest of the time spent outdoors is recommended. Clothing should allow insolation of at least 1/4 of the whole skin area. Conclusions . Avoiding near-noon solar radiation or using sunscreens with high SPF always while staying on the sun does not allow one to obtain a proper vitamin D status.

  6. A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon β-1b in patients with multiple sclerosis.

    Science.gov (United States)

    Soilu-Hänninen, Merja; Aivo, Julia; Lindström, Britt-Marie; Elovaara, Irina; Sumelahti, Marja-Liisa; Färkkilä, Markus; Tienari, Pentti; Atula, Sari; Sarasoja, Taneli; Herrala, Lauri; Keskinarkaus, Irma; Kruger, Johanna; Kallio, Timo; Rocca, Maria A; Filippi, Massimo

    2012-05-01

    To study the safety and efficacy of vitamin D3 as an add on therapy to interferon β-1b (IFNB) in patients with multiple sclerosis (MS). 1 year, double blind, placebo controlled, randomised study in 66 MS patients. The primary outcomes were T2 burden of disease (BOD) on MRI scans, proportion of patients with serum levels of 25-hydroxyvitamin D (25(OH)D) ≥85 nmol/l or intact parathyroid hormone (PTH) ≤20 ng/l, and number of adverse events. Secondary outcomes were number of MRI enhancing T1 lesions and new T2 lesions, annual relapse rate, changes in the Expanded Disability Status Scale score, timed 25 foot walk test and timed 10 foot tandem walk tests. Median change in BOD was 287 mm(3) in the placebo group and 83 mm(3) in the vitamin D group (p=0.105). Serum levels of 25(OH)D increased from a mean of 54 (range 19-82) nmol/l to 110 (range 67-163) nmol/l in the vitamin D group. 84% of patients reached a serum 25(OH)D level >85 nmol/l in the vitamin D group and 3% in the placebo group (pvitamin D group showed fewer new T2 lesions (p=0.286) and a significantly lower number of T1 enhancing lesions (p=0.004), as well as a tendency to reduced disability accumulation (p=0.071) and to improved timed tandem walk (p=0.076). There were no significant differences in adverse events or in the annual relapse rate. Vitamin D3 add on treatment to IFNB reduces MRI disease activity in MS. EudraCT number 2007-001958-99 and ClinicalTrialsGov number NCT01339676.

  7. 1(OH vitamin D3 supplementation improves the sensitivity of the immune-response during Peg-IFN/RBV therapy in chronic hepatitis C patients-case controlled trial.

    Directory of Open Access Journals (Sweden)

    Yasuteru Kondo

    Full Text Available OBJECTIVE: 1,25(OH2 vitamin D3 can affect immune cells. However, the mechanism responsible for the favorable effects of 1(OH vitamin D3, which becomes 1,25(OH2 vitamin D3 in the liver, is not clear. The aim of this study is to analyze the immunological response of 1(OH vitamin D3 supplementation in CH-C patients. DESIGN: Forty-two CH-C patients were treated with 1(OH vitamin D3/Peg-IFNα/RBV. Forty-two case-matched controls were treated with Peg-IFNα/RBV. The expression of Interferon-stimulated genes (ISGs-mRNA in the liver biopsy samples and JFH-1 replicating Huh-7 cells were quantified by real-time PCR. Ten kinds of cytokines in the plasma were quantified during treatment by using a suspension beads array. A trans-well co-culture system with peripheral blood mononuclear cells (PBMCs and Huh-7 cells was used to analyze the effect of 1(OH vitamin D3. The activities of the Th1 response were compared between subjects treated with 1(OH vitamin D3/Peg-IFN/RBV and those treated with Peg-IFN/RBV therapy alone. RESULTS: 1(OH vitamin D3/Peg-IFN/RBV treatment could induce rapid viral reduction, especially in IL28B T/T polymorphism. Several kinds of cytokines including IP-10 were significantly decreased after 4 weeks of 1(OH vitamin D3 treatment (p<0.05. Th1 responses in the subjects treated with 1(OH vitamin D3/Peg-IFN/RBV were significantly higher than those treated with Peg-IFN/RBV at 12 weeks after Peg-IFN/RBV therapy (p<0.05. The expression of ISGs in the patient's liver biopsy samples was significantly lower than in those treated without 1(OH vitamin D3 (p<0.05. CONCLUSION: 1(OH vitamin D3 could improve the sensitivity of Peg-IFN/RBV therapy on HCV-infected hepatocytes by reducing the IP-10 production from PBMCs and ISGs expression in the liver.

  8. The role of receptor topology in the vitamin D3 uptake and Ca{sup 2+} response systems

    Energy Technology Data Exchange (ETDEWEB)

    Morrill, Gene A., E-mail: gene.morrill@einstein.yu.edu; Kostellow, Adele B.; Gupta, Raj K.

    2016-09-02

    The steroid hormone, vitamin D{sub 3}, regulates gene transcription via at least two receptors and initiates putative rapid response systems at the plasma membrane. The vitamin D receptor (VDR) binds vitamin D{sub 3} and a second receptor, importin-4, imports the VDR-vitamin D{sub 3} complex into the nucleus via nuclear pores. Here we present evidence that the Homo sapiens VDR homodimer contains two transmembrane (TM) helices ({sup 327}E – D{sup 342}), two TM “half-helix” ({sup 264}K − N{sup 276}), one or more large channels, and 16 cholesterol binding (CRAC/CARC) domains. The importin-4 monomer exhibits 3 pore-lining regions ({sup 226}E – L{sup 251}; {sup 768}V – G{sup 783}; {sup 876}S – A{sup 891}) and 16 CRAC/CARC domains. The MEMSAT algorithm indicates that VDR and importin-4 may not be restricted to cytoplasm and nucleus. VDR homodimer TM helix-topology predicts insertion into the plasma membrane, with two 84 residue C-terminal regions being extracellular. Similarly, MEMSAT predicts importin-4 insertion into the plasma membrane with 226 residue extracellular N-terminal regions and 96 residue C-terminal extracellular loops; with the pore-lining regions contributing gated Ca{sup 2+} channels. The PoreWalker algorithm indicates that, of the 427 residues in each VDR monomer, 91 line the largest channel, including two vitamin D{sub 3} binding sites and residues from both the TM helix and “half-helix”. Cholesterol-binding domains also extend into the channel within the ligand binding region. Programmed changes in bound cholesterol may regulate both membrane Ca{sup 2+} response systems and vitamin D{sub 3} uptake as well as receptor internalization by the endomembrane system culminating in uptake of the vitamin D{sub 3}-VDR-importin-4 complex into the nucleus.

  9. Vitamin D3-Loaded Nanostructured Lipid Carriers as a Potential Approach for Fortifying Food Beverages; in Vitro and in Vivo Evaluation

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    Maryam Mohammadi

    2017-04-01

    Full Text Available Purpose: Nanostructured lipid carriers (NLCs composed of solid lipid and oil are a new generation of lipid nanoparticles which have exhibited some merits over traditional used lipid nanoparticles in fortifying food and beverages and nutraceuticals delivery systems such as liposomes and solid lipid nanoparticles. Methods: In this study, Precirol and Compritol as solid lipids, Miglyol and Octyloctanoat as liquid lipids, Tween80, Tween20 and Poloxamer407 as surfactants were used to prepare vitamin D3-loaded NLC dispersion using hot homogenization method. The particle size and size distribution for all formulations were evaluated by immediately after production and during a storage period of 60 days. Results: The Precirol-based NLC showed superiority over Compritol-based NLC in the point of physical stability. Results clearly suggested that an optimum concentration of 3% of Poloxamer407 or 2% of Tween20 was sufficient to cover the surface of nanoparticles effectively and prevent agglomeration during the homogenization process. Octyloctanoat was introduced for the first time as a good substituent for Miglyol in the preparation of NLC formulations. The vitamin D3 Intestinal absorption enhanced by the incorporating in NLCs. Conclusion: It was concluded that NLC showed a promising approach for fortifying beverages by lipophilic nutraceuticals such as vitamin D.

  10. Selective upregulation of the expression of plasma membrane calcium ATPase isoforms upon differentiation and 1,25(OH)2D3-vitamin treatment of colon cancer cells.

    Science.gov (United States)

    Ribiczey, Polett; Papp, Béla; Homolya, László; Enyedi, Ágnes; Kovács, Tünde

    2015-08-14

    We have previously presented co-expression of the plasma membrane calcium ATPase isoforms 4b (PMCA4b) and 1b (PMCA1b) in colon carcinoma cells, and selective upregulation of PMCA4b during differentiation initiated by short chain fatty acids or post-confluent growth. Here we show that the induction of PMCA4b expression is a characteristic feature of the post-confluency-induced differentiation of both enterocyte-type and goblet cell-type colon cancer cells. Vitamin D3 (1,25(OH)2D3) is a well-known regulator of intestinal Ca(2+) absorption and of basic cell functions such as growth and differentiation in various cell types. As PMCA proteins are involved both in intestinal Ca(2+) absorption and adenocarcinoma cell differentiation, we investigated the effect of 1,25(OH)2D3 on PMCA expression in enterocyte-like colon carcinoma cells, and monitored its effect on the expression of various differentiation markers. 1,25(OH)2D3 stimulated PMCA1b, but not PMCA4b expression without modulating the expression of the majority of the differentiation markers examined. Caco-2 cells differentiated in post-confluent cultures present normal enterocyte-like intestinal epithelial phenotype. To better understand the role of PMCA proteins in vectorial Ca(2+) transport by enterocytes, we also studied their subcellular localization in mature polarized Caco-2 cells. Both PMCA isoforms were located to the basolateral membrane, and the PMCA-specific immunofluorescent signal was significantly higher in vitamin D3-treated cells, underlining the 1,25(OH)2D3-induced upregulation of PMCA (presumably 1b isoform) expression in differentiated Caco-2 cells. We suggest that while PMCA1b has a housekeeping function in colon cancer cells, PMCA4b participates in the reorganization of the Ca(2+) signalling machinery during cell differentiation. The subcellular localization of PMCA1b and its selective 1,25(OH)2D3-dependent upregulation indicate that this isoform may have a specific role in 1,25(OH)2D3

  11. Clinical review: Effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: a systematic review and meta-analysis.

    Science.gov (United States)

    Seida, Jennifer C; Mitri, Joanna; Colmers, Isabelle N; Majumdar, Sumit R; Davidson, Mayer B; Edwards, Alun L; Hanley, David A; Pittas, Anastassios G; Tjosvold, Lisa; Johnson, Jeffrey A

    2014-10-01

    Observational studies report consistent associations between low vitamin D concentration and increased glycemia and risk of type 2 diabetes, but results of randomized controlled trials (RCTs) are mixed. The objective of the study was to systematically review RCTs that report on the effects of vitamin D supplementation on glucose homeostasis or diabetes prevention. Sources of data for the study were MEDLINE, EMBASE, SCOPUS, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment, and Science Citation Index from inception to June 2013. Study selection was trials that compared vitamin D3 supplementation with placebo or a non-vitamin D supplement in adults with normal glucose tolerance, prediabetes, or type 2 diabetes. Two reviewers collected data and assessed trial quality using the Cochrane Risk of Bias tool. Random-effects models were used to estimate mean differences (MDs) and odds ratios. The main outcomes of interest were homeostasis model assessment of insulin resistance, homeostasis model assessment of β-cell function, hemoglobin A1c levels, fasting blood glucose, incident diabetes, and adverse events. Thirty-five trials (43 407 patients) with variable risk of bias were included. Vitamin D had no significant effects on insulin resistance [homeostasis model assessment of insulin resistance: MD -0.04; 95% confidence interval (CI) -0.30 to 0.22, I-squared statistic (I(2)) = 45%], insulin secretion (homeostasis model of β-cell function: MD 1.64; 95% CI -25.94 to 29.22, I(2) = 40%), or hemoglobin A1c (MD -0.05%; 95% CI -0.12 to 0.03, I(2) = 55%) compared with controls. Four RCTs reported on the progression to new diabetes and found no effect of vitamin D (odds ratio 1.02; 95% CI 0.94 to 1.10, I(2) = 0%). Adverse events were rare, and there was no evidence of publication bias. Evidence from available trials shows no effect of vitamin D3 supplementation on glucose homeostasis or diabetes prevention

  12. Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU per day on biochemical responses and the wellbeing of patients

    Directory of Open Access Journals (Sweden)

    Hu Amanda

    2004-07-01

    Full Text Available Abstract Background For adults, vitamin D intake of 100 mcg (4000 IU/day is physiologic and safe. The adequate intake (AI for older adults is 15 mcg (600 IU/day, but there has been no report focusing on use of this dose. Methods We compared effects of these doses on biochemical responses and sense of wellbeing in a blinded, randomized trial. In Study 1, 64 outpatients (recruited if summer 2001 25(OHD Results In Study 1, basal summer 25-hydroxyvitamin D [25(OHD] averaged 48 ± 9 (SD nmol/L. Supplementation for more than 6 months produced mean 25(OHD levels of 79 ± 30 nmol/L for the 15 mcg/day group, and 112 ± 41 nmol/L for the 100 mcg/day group. Both doses lowered plasma parathyroid hormone with no effect on plasma calcium. Between December and February, wellbeing score improved more for the 100-mcg/day group than for the lower-dosed group (1-tail Mann-Whitney p = 0.036. In Study 2, 25(OHD averaged 39 ± 9 nmol/L, and winter wellbeing scores improved with both doses of vitamin D (two-tail p Conclusion The highest AI for vitamin D brought summertime 25(OHD to >40 nmol/L, lowered PTH, and its use was associated with improved wellbeing. The 100 mcg/day dose produced greater responses. Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing response, particularly for those on the lower dose. This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin D.

  13. Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial).

    Science.gov (United States)

    Avenell, Alison; MacLennan, Graeme S; Jenkinson, David J; McPherson, Gladys C; McDonald, Alison M; Pant, Puspa R; Grant, Adrian M; Campbell, Marion K; Anderson, Frazer H; Cooper, Cyrus; Francis, Roger M; Gillespie, William J; Robinson, C Michael; Torgerson, David J; Wallace, W Angus

    2012-02-01

    Vitamin D or calcium supplementation may have effects on vascular disease and cancer. Our objective was to investigate whether vitamin D or calcium supplementation affects mortality, vascular disease, and cancer in older people. The study included long-term follow-up of participants in a two by two factorial, randomized controlled trial from 21 orthopedic centers in the United Kingdom. Participants were 5292 people (85% women) aged at least 70 yr with previous low-trauma fracture. Participants were randomly allocated to daily vitamin D(3) (800 IU), calcium (1000 mg), both, or placebo for 24-62 months, with a follow-up of 3 yr after intervention. All-cause mortality, vascular disease mortality, cancer mortality, and cancer incidence were evaluated. In intention-to-treat analyses, mortality [hazard ratio (HR) = 0.93; 95% confidence interval (CI) = 0.85-1.02], vascular disease mortality (HR = 0.91; 95% CI = 0.79-1.05), cancer mortality (HR = 0.85; 95% CI = 0.68-1.06), and cancer incidence (HR = 1.07; 95% CI = 0.92-1.25) did not differ significantly between participants allocated vitamin D and those not. All-cause mortality (HR = 1.03; 95% CI = 0.94-1.13), vascular disease mortality (HR = 1.07; 95% CI = 0.92-1.24), cancer mortality (HR = 1.13; 95% CI = 0.91-1.40), and cancer incidence (HR = 1.06; 95% CI = 0.91-1.23) also did not differ significantly between participants allocated calcium and those not. In a post hoc statistical analysis adjusting for compliance, thus with fewer participants, trends for reduced mortality with vitamin D and increased mortality with calcium were accentuated, although all results remain nonsignificant. Daily vitamin D or calcium supplementation did not affect mortality, vascular disease, cancer mortality, or cancer incidence.

  14. In Vitro Differentiation of Preosteoblast-Like Cells, MC3T3-E1, to Adipocytes Is Enhanced by 1,25(OH2 Vitamin D3

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    Elisha Pendleton

    2017-06-01

    Full Text Available Osteoblasts and adipocytes originate from common mesenchymal progenitor cells and are controlled by specific transcription factors. While 1,25-dihydroxyvitamin D3 (vitamin D is known to be an important factor for osteoblast differentiation, there are conflicting reports regarding its effect on adipogenesis. In this study, we attempted to understand the effect of exposure of preosteoblasts (MC3T3-E1 to adipogenic media with and without vitamin D and determined the expression of adipogenic genes during this process. Our studies show that while transdifferentiation of preosteoblasts occurred on exposure to adipogenic media, the effect of vitamin D treatment was synergistic resulting in several hundred fold increase in adipocyte transcription factors C/EBPα and peroxisome proliferator-activated receptor-gamma (P < 0.001 along with an increase in markers of adipogenesis and accumulation of lipid droplets in cells. Vitamin D treatment was also accompanied by 100-fold to 700-fold increases in vitamin D receptor expression during the treatment period (P < 0.001. To determine how the effect of vitamin D might compare to other genetic manipulations that promote adipogenic differentiation, we stably knocked down retinoblastoma expression in MC3T3-E1 cells. Recent studies have suggested retinoblastoma (Rb1 tumor suppressor gene function to be critical to maintain osteoblasts function and inhibit adipocyte differentiation. We exposed MC3T3-E1 cells with reduced Rb1 expression to adipogenic media and found an increase in adipogenic differentiation when compared to cells with a full complement of Rb dosage. However, the extent of the change was not as dramatic as seen with vitamin D. These studies show that preosteoblasts are sensitive and respond to these manipulations that favor the adipocytic phenotype. While vitamin D is not known to directly affect targets in adipogenesis, our observations may have resulted from the malleability of preosteoblast

  15. Supplementation of docosahexaenoic acid (DHA), vitamin D3 and uridine in combination with six weeks of cognitive and motor training in prepubescent children: a pilot study

    DEFF Research Database (Denmark)

    Hansen, Solvejg Lis; Ritterband-Rosenbaum, Anina; Voigt, Camilla B.

    2017-01-01

    program with dietary supplementation consisting of 500 mg docosahexaenoic acid (DHA), 10 μg vitamin D3 and 1000 mg uridine (DDU-supplement) in 16 prepubescent children (age 8–11 years). Methods We designed a randomized, placebo-controlled, double-blinded study lasting 6 weeks in which DDU-supplement...... tests were performed. Results Fourteen of the 16 children completed the intervention and ingested the supplement as required. 6 weeks DDU-supplementation resulted in a significant increase in the blood concentration of vitamin D2+3 and DHA (p = 0.023 and p ...Background Learning and memory have been shown to be influenced by combination of dietary supplements and exercise in animal models, but there is little available evidence from human subjects. The aim of this pilot study was to investigate the effect of combining a motor- and cognitive exercise...

  16. Blood vitamin D(3) metabolite concentrations of adult female bearded dragons (Pogona vitticeps) remain stable after ceasing UVb exposure

    NARCIS (Netherlands)

    Oonincx, D G A B; van de Wal, M D; Bosch, Guido; Stumpel, J B G; Heijboer, A C; van Leeuwen, J P T M; Hendriks, W H; Kik, M

    Vitamin D deficiency can lead to several health problems collectively called metabolic bone disease (MBD). One commonly kept reptile species prone to develop MBD if managed incorrectly is the bearded dragon (Pogona vitticeps). This study aimed to determine the extent to which adult female bearded

  17. Blood vitamin D(3) metabolite concentrations of adult female bearded dragons (Pogona vitticeps) remain stable after ceasing UVb exposure

    NARCIS (Netherlands)

    Oonincx, D.G.A.B.; Wal, van de M.D.; Bosch, G.; Stumpel, J.B.G.; Heijboer, A.C.; Leeuwen, van J.P.T.M.; Hendriks, W.H.; Kik, M.

    2013-01-01

    Vitamin D deficiency can lead to several health problems collectively called metabolic bone disease (MBD). One commonly kept reptile species prone to develop MBD if managed incorrectly is the bearded dragon (Pogona vitticeps). This study aimed to determine the extent to which adult female bearded

  18. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis.

    Science.gov (United States)

    Burton, J M; Kimball, S; Vieth, R; Bar-Or, A; Dosch, H-M; Cheung, R; Gagne, D; D'Souza, C; Ursell, M; O'Connor, P

    2010-06-08

    Low vitamin D status has been associated with multiple sclerosis (MS) prevalence and risk, but the therapeutic potential of vitamin D in established MS has not been explored. Our aim was to assess the tolerability of high-dose oral vitamin D and its impact on biochemical, immunologic, and clinical outcomes in patients with MS prospectively. An open-label randomized prospective controlled 52-week trial matched patients with MS for demographic and disease characteristics, with randomization to treatment or control groups. Treatment patients received escalating vitamin D doses up to 40,000 IU/day over 28 weeks to raise serum 25-hydroxyvitamin D [25(OH)D] rapidly and assess tolerability, followed by 10,000 IU/day (12 weeks), and further downtitrated to 0 IU/day. Calcium (1,200 mg/day) was given throughout the trial. Primary endpoints were mean change in serum calcium at each vitamin D dose and a comparison of serum calcium between groups. Secondary endpoints included 25(OH)D and other biochemical measures, immunologic biomarkers, relapse events, and Expanded Disability Status Scale (EDSS) score. Forty-nine patients (25 treatment, 24 control) were enrolled [mean age 40.5 years, EDSS 1.34, and 25(OH)D 78 nmol/L]. All calcium-related measures within and between groups were normal. Despite a mean peak 25(OH)D of 413 nmol/L, no significant adverse events occurred. Although there may have been confounding variables in clinical outcomes, treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls. High-dose vitamin D (approximately 10,000 IU/day) in multiple sclerosis is safe, with evidence of immunomodulatory effects. This trial provides Class II evidence that high-dose vitamin D use for 52 weeks in patients with multiple sclerosis does not significantly increase serum calcium levels when compared to patients not on high-dose supplementation. The trial, however, lacked statistical precision and the

  19. Nuclear xenobiotic receptor pregnane X receptor locks corepressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) onto the CYP24A1 promoter to attenuate vitamin D3 activation.

    Science.gov (United States)

    Konno, Yoshihiro; Kodama, Susumu; Moore, Rick; Kamiya, Nobuhiro; Negishi, Masahiko

    2009-02-01

    We have studied the molecular mechanism by which the nuclear xenobiotic receptors pregnane X receptor (PXR) and constitutive active/androstane receptor (CAR) regulate transcription of the vitamin D(3) 24-hydroxylase (CYP24A1) gene. In the absence of vitamin D(3), PXR activates the CYP24A1 gene by directly binding to and transactivating vitamin D-response elements (VDREs) within its promoter. Vitamin D(3) activates the CYP24A1 promoter by dissociating the corepressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) from the vitamin D receptor (VDR) on those VDREs. PXR strongly represses vitamin D(3) activation of the CYP24A1 gene, in which PXR indirectly binds to and prevents vitamin D(3)-dependent dissociation of SMRT from the CYP24A1 promoter. The degree of the PXR-mediated locking of SMRT depends on the relative concentration of vitamin D(3) to the human PXR activator rifampicin; SMRT increased its dissociation as this ratio increased. CAR is also found to prevent dissociation of SMRT from the CYP24A1 promoter. Thus, our present study defines the novel molecular mechanism by which PXR and CAR mediate drug interactions with vitamin D(3) to regulate the CYP24A1 gene. Pxr(+/+) and Pxr(-/-) mice were continuously treated with mouse PXR activator PCN to evaluate the hypothesis that induction of the Cyp24a1 gene is responsible for the loss of bone mineral density often observed in patients treated continuously with PXR-activating drugs. PCN-dependent loss of mineral density is observed in the metaphyseal bones of only the Pxr(+/+) mice. This loss, however, does not correlate with the expression levels of the Cyp24a1 gene in these mice.

  20. Interspecies differences in plasma concentrations of 25-hydroxyvitamin D3 and dermal Vitamin D synthesis of kiwi (Apteryx mantelli), tuatara (Sphenodon punctatus), and New Zealand sea lions (Phocarctos hookeri).

    Science.gov (United States)

    Kale, Madhumita S; Dittmer, Keren E; Roe, Wendi D; Gartrell, Brett D

    2017-07-28

    Vitamin D plays a central role in calcium homeostasis of most vertebrates, and is obtained in different species through diet, dermal synthesis, or a combination of both. The aim of this study was to determine the predominant routes of Vitamin D synthesis in three disparate species, brown kiwi (Apteryx mantelli), tuatara (Sphenodon punctatus), and New Zealand sea lions (Phocarctos hookeri). We surveyed plasma concentrations of 25-hydroxyvitamin D2 and D3, analysed environmental conditions and life history factors, and determined the ability of skin samples to synthesise Vitamin D3 on exposure to ultraviolet-B radiation. There was variation in the plasma/serum 25-hydroxyvitamin D3 concentrations between and within the species studied, with wild kiwi having the lowest concentrations and NZ sea lions the highest. Kiwi skin produced small but measurable amounts of Vitamin D3, while tuatara skin produced Vitamin D3 concentrations higher than that of kiwi. New Zealand sea lion skin produced the highest amount of Vitamin D3 and differed from the other two species in this study in that Vitamin D3 was present in skin before UV-B exposure. The results from this study show that all three species studied retained the ability to use both dietary and dermal sources of Vitamin D, although there was interspecies variation in the magnitude of dermal synthesis. Comparisons between these species show that there are differences in their Vitamin D pathways, but suggest that there are more factors contributing to these pathways than might be expected solely from life history characteristics.

  1. Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial.

    Science.gov (United States)

    Kampman, Margitta T; Steffensen, Linn H; Mellgren, Svein I; Jørgensen, Lone

    2012-08-01

    High vitamin D levels may reduce the risk of relapses and disease progression in multiple sclerosis. This 96-week randomised controlled trial was designed to assess the effect of vitamin D(3) supplementation on bone mineral density in persons with multiple sclerosis. Supplementation with 20,000 IU vitamin D(3) weekly raised median serum 25-hydroxy vitamin D (25[OH]D) to 121 nmol/L. The modified intention to treat analysis included 35 persons in the vitamin D(3) group and 33 in the placebo group. Participants were age 21 to 50 years and fully ambulatory (median Expanded Disability Status Scale (EDSS) 2.5). We studied the effect of supplementing vitamin D(3) on the exploratory outcomes annualised relapse rate (ARR), EDSS, multiple sclerosis functional composite (MSFC) components, grip strength, and fatigue. After 96 weeks, there was no significant difference between groups in ARR (absolute difference 0.10, 95% CI -0.07 to 0.27; p = 0.25), EDSS (absolute difference -0.01, 95% CI -0.35 to 0.35; p = 0.97), MSFC components, grip strength, or fatigue. Supplementation with 20,000 IU vitamin D(3) weekly did not result in beneficial effects on the measured multiple sclerosis-related outcomes. This study was not powered to address clinical outcomes, but none of the results were suggestive of an effect in this unselected population of fully ambulatory persons with multiple sclerosis.

  2. Effect of High-Dose Vitamin D3 Intake on Ambulation, Muscular Pain and Bone Mineral Density in a Woman with Multiple Sclerosis: A 10-Year Longitudinal Case Report

    NARCIS (Netherlands)

    Van Amerongen, B.M.; Feron, F.

    2012-01-01

    Mounting evidence correlate vitamin D3 (cholecalciferol) supplementation or higher serum levels of vitamin D (25(OH)D) with a lower risk of developing multiple sclerosis (MS), reduced relapse rate, slower progression or fewer new brain lesions. We present here the case of a woman who was diagnosed

  3. Vitamin D (25-0H D3) status and pathological response to neoadjuvant chemotherapy in stage II/III breast cancer: Data from the NEOZOTAC trial (BOOG 10-01)

    NARCIS (Netherlands)

    Charehbili, A.; Hamdy, N. A. T.; Smit, V. T. H. B. M.; Kessels, L.; van Bochove, A.; van Laarhoven, H. W.; Putter, H.; Meershoek-Klein Kranenbarg, E.; van Leeuwen-Stok, A. E.; van der Hoeven, J. J. M.; van de Velde, C. J. H.; Nortier, J. W. R.; Kroep, J. R.

    2016-01-01

    Serum levels of 25-OH vitamin D3 (vitamin D) have been shown to be prognostic for disease-free survival in patients with breast cancer. We investigated the predictive value of these levels for pathological response after neoadjuvant chemotherapy in patients with breast cancer taking part in the

  4. Vitamin D (25-0H D3) status and pathological response to neoadjuvant chemotherapy in stage II/III breast cancer: Data from the NEOZOTAC trial (BOOG 10-01)

    NARCIS (Netherlands)

    Charehbili, A.; Hamdy, N.A.; Smit, V.T.; Kessels, L; Bochove, A. van; Laarhoven, H.W.M. van; Putter, H.; Meershoek-Klein Kranenbarg, E.; Leeuwen-Stok, A.E. van; Hoeven, J.J.M. van der; Velde, C.J. van de; Nortier, J.W.; Kroep, J.R.

    2016-01-01

    BACKGROUND: Serum levels of 25-OH vitamin D3 (vitamin D) have been shown to be prognostic for disease-free survival in patients with breast cancer. We investigated the predictive value of these levels for pathological response after neoadjuvant chemotherapy in patients with breast cancer taking part

  5. Polyvalent immunoglobulins with vitamin D3 and vitamin B12 in the treatment of Sjogren's syndrome in a vegetarian with stomatitis, glossodynia, xerostomia, and elevated antinuclear antibodies: Case report
.

    Science.gov (United States)

    Cuny, Clemens; Vaerst, Barbara; Gabrielpillai, Jennis; Tahtali, Aykut; Balster, Sven; Lissner, Reinhard; Woodcock, Barry G

    2018-01-01

    Sjogren's syndrome, involving sicca symptoms with xerostomia, stomatitis, and considerable pain is a difficult-to-treat autoimmune disease where the treatment options are limited and, as in the case of methotrexate, have a low therapeutic index. This case report concerns a male patient, aged 75 years and vegetarian, with Sjogren's syndrome subsequently confirmed by salivary gland biopsy. Serum antinuclear antibodies (ANA) were elevated (1 : 320). Low serum vitamin B12 and iron levels could be improved after 20 days using vitamin B12 and iron oral supplements. Despite symptomatic treatment, xerostomia, glossitis, and glossodynia were still present, at times marked, after 12 months when the ANA titer was unchanged. Following treatment with an anti-inflammatory polyvalent immunoglobulin formulation (Lactobin®N, 7 g daily), a bovine colostrum concentrate given orally in combination with oral vitamin D3 (2,000 IU daily), sicca symptoms and xerostomia progressively decreased and at day 750 were confined to occasional and minor glossitis of the upper lip. This case report demonstrates the satisfactory control of Sjogren's syndrome using oral polyvalent immunoglobulins with vitamin D3. In contrast to treatment options involving antimalarial drugs and methotrexate, there are no safety issues in patients tolerant to milk products.
.

  6. Network of nuclear receptor ligands in multiple sclerosis: Common pathways and interactions of sex-steroids, corticosteroids and vitamin D3-derived molecules.

    Science.gov (United States)

    Rolf, Linda; Damoiseaux, Jan; Hupperts, Raymond; Huitinga, Inge; Smolders, Joost

    2016-09-01

    Sex-steroids, corticosteroids and vitamin D3-derived molecules have all been subject to experimental studies and clinical trials in a plethora of autoimmune diseases. These molecules are all derived from cholesterol metabolites and are ligands for nuclear receptors. Ligation of these receptors results in direct regulation of multiple gene transcription involved in general homeostatic and adaptation networks, including the immune system. Indeed, the distinct ligands affect the function of both myeloid and lymphoid cells, eventually resulting in a less pro-inflammatory immune response which is considered beneficial in autoimmune diseases. Next to the immune system, also the central nervous system is prone to regulation by these nuclear receptor ligands. Understanding of the intricate interactions between sex-steroids, corticosteroids and vitamin D3 metabolites, on the one hand, and the immune and central nervous system, on the other hand, may reveal novel approaches to utilize these nuclear receptor ligands to full extent as putative treatments in multiple sclerosis, the prototypic immune-driven disease of the central nervous system. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Roosters affected by epididymal lithiasis present local alteration in vitamin D3, testosterone and estradiol levels as well as estrogen receptor 2 (beta) expression.

    Science.gov (United States)

    Oliveira, André G; Dornas, Rubem A P; Praes, Lílian C; Hess, Rex A; Mahecha, Germán A B; Oliveira, Cleida A

    2011-09-01

    Epididymal lithiasis is a reproductive dysfunction of roosters that is associated with loss of fertility and is characterized by the formation of calcium stones in the lumen of the efferent ductules of the epididymal region. The efferent ductules of birds are responsible for the reabsorption of the fluid coming from the testis as well as luminal calcium. It has been hypothesized that the epididymal stone formation may be related to the impairment of local fluid or calcium homeostasis, which depends on hormones such as estradiol (E(2)). Therefore, this study aimed to investigate possible alterations in the expression of ERα (ESR1) and ERβ (ESR2) in the epididymal region of roosters affected by epididymal lithiasis. The study was performed by immunohistochemistry and western blotting assays. In addition, the concentrations of E(2), vitamin D3, and testosterone, which are also key hormones in maintenance of calcium homeostasis, were determined in the plasma and epididymal region, by ELISA. It was observed that ESR2 expression is increased in all segments of the epididymal region of affected roosters, whereas ESR1 levels are not altered. Moreover, the hormone concentration profiles were changed, as in the epididymal region of roosters with lithiasis the E(2) levels were increased and vitamin D3 as well as testosterone concentrations were significantly decreased. These results suggest that a hormonal imbalance may be involved with the origin and progression of the epididymal lithiasis, possibly by affecting the local fluid or calcium homeostasis.

  8. Dynamics of Bone Metabolism Markers Serum Level in Children with Bronchial Asthma on the Background of Vitamin D3 and Calcium Salt Supplementation

    Directory of Open Access Journals (Sweden)

    A.O. Vertehel

    2016-03-01

    Full Text Available The aim: to optimize the diagnosis of the calcium-phosphorus metabolism disorders and to control the effectiveness of therapeutic and prophylactic use of vitamin D and calcium in children with bronchial asthma. Materials and methods. A total of 120 children in 2 groups, 60 subjects in each, were examined: 1 — children with bronchial asthma; 2 — apparently healthy children (control group. Two courses of therapy with solution of vitamin D3 and calcium carbonate/citrate were applied: 4 weeks — 2,000 IU and 1,000 mg per day, respectively; 8 weeks — 1,000 IU and 500 mg a day, respectively. Results. Among children with bronchial asthma, there was a decrease in the number of patients with normal serum levels of total calcium (P < 0.05, osteocalcin (P < 0.05, parathyroid hormone (P < 0.05, collagen type 1 C-telopeptides (P < 0.05, 25(OHD (P < 0.05, alkaline phosphatase activity (P < 0.05. After 1 month of therapy, the number of children with normal alkaline phosphatase activity (P < 0.05, osteocalcin (P < 0.05, collagen type 1 C-telopeptides (P < 0.05 increased; in 3 months — total calcium (P < 0.05, 25(OHD (P < 0.05. Conclusions. The use of vitamin D3 and calcium solution normalizes bone metabolism parameters in children with bronchial asthma. The optimal time to control the effectiveness of medical recovery of bone metabolism in children with bronchial asthma is 3 months.

  9. 20-Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes.

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    Zorica Janjetovic

    Full Text Available The side chain of vitamin D3 is hydroxylated in a sequential manner by cytochrome P450scc (CYP11A1 to form 20-hydroxycholecalciferol, which can induce growth arrest and differentiation of both primary and immortalized epidermal keratinocytes. Since nuclear factor-kappaB (NF-kappaB plays a pivotal role in the regulation of cell proliferation, differentiation and apoptosis, we examined the capability of 20-hydroxycholecalciferol to modulate the activity of NF-kappaB, using 1,25-dihydroxycholecalciferol (calcitriol as a positive control. 20-hydroxycholecalciferol inhibits the activation of NFkappaB DNA binding activity as well as NF-kappaB-driven reporter gene activity in keratinocytes. Also, 20-hydroxycholecalciferol induced significant increases in the mRNA and protein levels of the NF-kappaB inhibitor protein, IkappaB alpha, in a time dependent manner, while no changes in total NF-kappaB-p65 mRNA or protein levels were observed. Another measure of NF-kappaB activity, p65 translocation from the cytoplasm into the nucleus was also inhibited in extracts of 20-hydroxycholecalciferol treated keratinocytes. Increased IkappaB alpha was concomitantly observed in cytosolic extracts of 20-hydroxycholecalciferol treated keratinocytes, as determined by immunoblotting and immunofluorescent staining. In keratinocytes lacking vitamin D receptor (VDR, 20-hydroxycholecalciferol did not affect IkappaB alpha mRNA levels, indicating that it requires VDR for its action on NF-kappaB activity. Comparison of the effects of calcitrol, hormonally active form of vitamin D3, with 20-hydrocholecalciferol show that both agents have a similar potency in inhibiting NF-kappaB. Since NF-kappaB is a major transcription factor for the induction of inflammatory mediators, our findings indicate that 20-hydroxycholecalciferol may be an effective therapeutic agent for inflammatory and hyperproliferative skin diseases.

  10. Vitamin D-3 and vitamin K-1 supplementation of Dutch postmenopausal women with normal and low bone mineral densities : effects on serum 25-hydroxyvitamin D and carboxylated osteocalcin

    NARCIS (Netherlands)

    Schaafsma, A; Muskiet, FAJ; Storm, H; Hofstede, GJH; Pakan, [No Value; Van der Veer, E

    Objective: Improvement of vitamin D and K status of about 60-y-old postmenopausal Dutch women. Design: In a randomized study postmenopausal women with normal (T-score >-1; n = 96) and low (T-score less than or equal to-1; n = 45) bone mineral density (BMD) of the lumbar spine, were supplemented with

  11. Medium doses of daily vitamin D decrease falls and higher doses of daily vitamin D3 increase falls: A randomized clinical trial.

    Science.gov (United States)

    Smith, Lynette M; Gallagher, J Christopher; Suiter, Corinna

    2017-10-01

    Falls are a serious health problem in the aging population. Because low levels of vitamin D have been associated with increased fall rates, many trials have been performed with vitamin D; two meta-analyses showed either a small effect or no effect of vitamin D on falls. We conducted a study of the effect of vitamin D on serum 25 hydroxyvitamin D (25OHD) and data on falls was collected as a secondary outcome. In a 12-month double blind randomized placebo trial, elderly women, mean age 66 years, were randomized to one of seven daily oral doses of vitamin D or placebo. The main inclusion criterion for study was a baseline serum 25OHDvitamin D on falls followed a U-shaped curve whether analyzed by dose or serum 25OHD levels. There was no decrease in falls on low vitamin D doses 400, 800 IU, a significant decrease on medium doses 1600, 2400,3200 IU (p=0.020) and no decrease on high doses 4000, 4800 IU compared to placebo (p=0.55). When compared to 12-month serum 25OHD quintiles, the faller rate was 60% in the lowest quintile <25ng/ml (<50nmol/L), 21% in the low middle quintile 32-38ng/ml (80-95nmo/L), 72% in the high middle quintile 38-46ng/ml (95-115nmo/L) and 45% in the highest quintile 46-66ng/ml (115-165nmol/L). In the subgroup with a fall history, fall rates were 68% on low dose, 27% on medium doses and 100% on higher doses. Fall rates on high doses were increased compared to medium doses (Odds Ratio 5.6.95% CI: 2.1-14.8). In summary, the maximum decrease in falls corresponds to a 12- month serum 25OHD of 32-38ng/ml (80-95nmol/L) and faller rates increase as serum 25OHD exceed 40-45ng/ml (100-112.5nmol/L). The Tolerable upper limit (TUL) recently increased in 2010 from 2000 to 4000 IU/day may need to be reduced in elderly women especially in those with a fall history. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Effect of 1,25-Dihydroxy Vitamin D3 on the Expression of Interleukin-17 and -21 in an Asthma Mice Model

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    RJ Lin

    2015-09-01

    Full Text Available Objective: To explore the effect of 1,25-dihydroxy vitamin D3 (1,25(OH2D3 on the expression of interleukin (IL-17 and IL-21 in asthma by establishing an asthma mice model. Methods: Forty female Kunming mice were randomly divided into normal control group (group A, n = 10, asthma group (group B, n = 10, 1,25(OH2D3 intervention group (group C, n = 10 and dexamethasone treatment group (group D, n = 10. Asthma mice model was established and subsequently treated with different intervention. The airway lesions in mice were observed and the serum IL-17, IL-21 and immunoglobulin E (IgE levels were determined using the enzyme-linked immunosorbent assay (ELISA method. Immunohistochemical method was used to detect the expression of IL-17 and IL-21 in lung tissues. Results:Serum IL-17 and IgE levels in groups B, C and D were remarkably higher than those in group A, especially in group B (F = 31.276, 18.677, p < 0.01. However, serum IL-21 level in group A was the highest, significantly higher than the other three groups (F = 22.406, p < 0.01. Immunohistochemical test revealed that the expression of IL-17 in group B was significantly higher than that in groups A, C and D, while IL-21 was strongly expressed in groups A and D but weakly expressed in group B. Conclusion: In the pathogenesis of asthma, 1,25(OH2D3 intervention can reduce the expression of IL-17 but elevate the expression of IL-21, suggesting it has a certain effect on asthma.

  13. Noncalcemic adverse effects and withdrawals in randomized controlled trials of long-term vitamin D2 or D3 supplementation: a systematic review and meta-analysis.

    Science.gov (United States)

    Malihi, Zarintaj; Wu, Zhenqiang; Mm Lawes, Carlene; Scragg, Robert

    2017-12-01

    Recent randomized controlled trials (RCTs) provide evidence for a possible beneficial impact of vitamin D supplementation on health outcomes beyond bone health, but there are few reviews of noncalcemic adverse effects from long-term supplementation. The aims of this systematic review of vitamin D supplementation in RCTs were as follows: to determine whether all adverse effects, when combined, are reported equally between treatment arms; to identify the most common noncalcemic adverse effects reported; and to ascertain whether withdrawal rates, as a marker of clinical adverse effects, differ between treatment arms. The MEDLINE Ovid, Embase, and Cochrane Library databases were searched systematically up to May 2016. Randomized controlled trials that met the following criteria were selected: administered vitamin D2 or D3 supplements for a minimum supplementation or follow-up period of 24 weeks, had a placebo/control group, and were conducted among adults (≥ 18 y). Two researchers independently screened studies for eligibility, extracted data, and carried out quality assessment of selected studies. A total of 128 studies with 52 297 participants were identified. A random-effects model was used to calculate risk ratios in a meta-analysis. Long-term vitamin D2 or D3 supplementation, compared with placebo, did not increase all adverse effects, when combined, as reported in 62 studies with 19 389 participants (relative risk [RR] = 0.97; 95%CI, 0.92-1.02). Vitamin D also did not increase the risk of the most common noncalcemic adverse effects: gastrointestinal symptoms were reported in 27 studies with 9189 participants (RR = 1.01; 95%CI, 0.87-1.17), and dermatological symptoms were reported in 8 studies with 1695 participants (RR = 1.33; 95%CI, 0.82-2.15). Vitamin D did not increase withdrawals from 123 studies with 41 861 participants (RR = 1.03; 95%CI, 0.96-1.09). However, participants given vitamin D were more likely to report withdrawals than

  14. Determinação de 25-hidroxivitamina D2 e D3 em plasma por CLAE-DAD Determination of 25-hidroxy-vitamin D2 and D3 in plasma by HPLC-DAD

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    Daiana Manuele Kich

    2012-10-01

    Full Text Available INTRODUÇÃO: O interesse pela vitamina D nos últimos anos teve aumento significativo. Estudos epidemiológicos realizados têm demonstrado um crescente aumento da deficiência de vitamina D entre a população. O marcador diagnóstico de escolha para determinar os níveis de vitamina D é a concentração de 25-hidroxivitamina D (25(OHD, com suas frações D2 (25(OHD2 e D3 (25(OHD3. OBJETIVO: Desenvolver uma metodologia analítica empregando cromatografia líquida de alta eficiência com detector de arranjo de diodos (CLAE-DAD para a determinação de 25(OHD3 e 25(OHD2 em plasma. MATERIAIS E MÉTODOS: 25(OHD3 e 25(OHD2 foram extraídos das amostras de plasma com hexano, utilizando-se dodecafenona como padrão interno (PI. Utilizou-se coluna analítica ACE 5 C18 com partículas de 5 µm e dimensões de 150 × 4,6 mm, fase móvel metanol-água (80:20; v/v e quantificação em 265 nm. RESULTADOS: A exatidão foi entre 98,4 e 107,5%. A precisão intraensaios esteve entre 6,5% e 9,2% para 25(OHD3 e entre 3,7% e 8,7% para 25(OHD2. A precisão interensaios esteve entre 2,9% e 6% para 25(OHD3 e entre 4% e 4,5% para 25(OHD2. O limite inferior de quantificação foi 10 ng/ml. As concentrações encontradas em amostras de 32 pacientes idosos estiveram entre 10,1 e 32,4 ng/ml, caracterizando deficiência de vitamina D nesse grupo. DISCUSSÃO O método foi capaz de quantificar 25(OHD2 e 25(OHD3 com uma preparação de amostra relativamente simples e rápida. O método foi seletivo, com separação adequada dos metabólitos e do padrão interno e sem presença de interferentes. CONCLUSÃO: O método desenvolvido apresenta desempenho analítico adequado e pode ser aplicado em condições clínicas.INTRODUCTION: The interest in vitamin D has increased significantly in recent years. Epidemiological studies conducted over the past 25 years have shown a steady increase in vitamin D deficiency. The diagnostic marker of choice to determine vitamin D levels is the

  15. Monochromatic excimer light versus combination of topical steroid with vitamin D3 analogue in the treatment of nonsegmental vitiligo: a randomized blinded comparative study.

    Science.gov (United States)

    Abdel Latif, Azmy Ahmed; Ibrahim, Shady Mahmoud Attia

    2015-01-01

    Vitiligo is a difficult disease to treat, socially stigmatizing its patients. Monochromatic excimer light (MEL) was developed for use in dermatology and adapted for the treatment of vitiligo. Comparing the efficacy of MEL versus topical combination therapy of vitamin D3 analogue and steroid in the treatment of nonsegmental vitiligo. Forty-four patients with localized and stable nonsegmental vitiligo participated in the present study. In each patient, two lesions were selected and divided randomly into two groups, group A was treated with daily topical combination of calcipotriol and betamethasone and group B was treated with biweekly sessions of MEL for 3 months. Efficacy based on repigmentation percentages were blindly evaluated by two independent physicians and patient's satisfaction. There was significant improvement in both treatment modalities at the end of the study, but without significant differences in both groups. There was a significant difference between both groups regarding the onset of repigmentation (p-value vitiligo. © 2015 Wiley Periodicals, Inc.

  16. Daily supplementation with 15 μg vitamin D2compared with vitamin D3to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial.

    Science.gov (United States)

    Tripkovic, Laura; Wilson, Louise R; Hart, Kathryn; Johnsen, Sig; de Lusignan, Simon; Smith, Colin P; Bucca, Giselda; Penson, Simon; Chope, Gemma; Elliott, Ruan; Hyppönen, Elina; Berry, Jacqueline L; Lanham-New, Susan A

    2017-08-01

    Background: There are conflicting views in the literature as to whether vitamin D 2 and vitamin D 3 are equally effective in increasing and maintaining serum concentrations of 25-hydroxyvitamin D [25(OH)D], particularly at lower doses of vitamin D. Objective: We aimed to investigate whether vitamin D 2 or vitamin D 3 fortified in juice or food, at a relatively low dose of 15 μg/d, was effective in increasing serum total 25(OH)D and to compare their respective efficacy in South Asian and white European women over the winter months within the setting of a large randomized controlled trial. Design: A randomized, double-blind, placebo-controlled food-fortification trial was conducted in healthy South Asian and white European women aged 20-64 y ( n = 335; Surrey, United Kingdom) who consumed placebo, juice supplemented with 15 μg vitamin D 2 , biscuit supplemented with 15 μg vitamin D 2 , juice supplemented with 15 μg vitamin D 3 , or biscuit supplemented with 15 μg vitamin D 3 daily for 12 wk. Serum 25(OH)D was measured by liquid chromatography-tandem mass spectrometry at baseline and at weeks 6 and 12 of the study. Results: Postintervention in the 2 ethnic groups combined, both the vitamin D 3 biscuit and the vitamin D 3 juice groups showed a significantly greater absolute incremental change (Δ) in total 25(OH)D when compared with the vitamin D 2 biscuit group [Δ (95% CI): 15.3 nmol/L (7.4, 23.3 nmol/L) ( P vitamin D 2 juice group [Δ (95% CI): 16.3 nmol/L (8.4, 24.2 nmol/L) ( P vitamin D relevant to public health recommendations (15 μg) and in vehicles relevant to food-fortification strategies, vitamin D 3 was more effective than vitamin D 2 in increasing serum 25(OH)D in the wintertime. Vitamin D 3 may therefore be a preferential form to optimize vitamin D status within the general population. This trial was registered at www.controlled-trials.com as ISRCTN23421591. © 2017 American Society for Nutrition.

  17. Effect of High-Dose Vitamin D3 Intake on Ambulation, Muscular Pain and Bone Mineral Density in a Woman with Multiple Sclerosis: A 10-Year Longitudinal Case Report

    Directory of Open Access Journals (Sweden)

    François Feron

    2012-10-01

    Full Text Available Mounting evidence correlate vitamin D3 (cholecalciferol supplementation or higher serum levels of vitamin D (25(OHD with a lower risk of developing multiple sclerosis (MS, reduced relapse rate, slower progression or fewer new brain lesions. We present here the case of a woman who was diagnosed with MS in 1990. From 1980 to 2000, her ability to walk decreased from ~20 to 1 km per day. Since January 2001, a vitamin D3 supplement was ingested daily. The starting dose was 20 mcg (800 IU/day and escalated to 100 mcg (4000 IU/day in September 2004 and then to 150 mcg (6000 IU/day in December 2005. Vitamin D3 intake reduced muscular pain and improved ambulation from 1 (February 2000 to 14 km/day (February 2008. Vitamin D intake over 10 years caused no adverse effects: no hypercalcaemia, nephrolithiasis or hypercalciuria were observed. Bowel problems in MS may need to be addressed as they can cause malabsorption including calcium, which may increase serum PTH and 1,25(OH2D levels, as well as bone loss. We suggest that periodic assessment of vitamin D3, calcium and magnesium intake, bowel problems and the measurement of serum 25(OHD, PTH, Ca levels, UCa/Cr and bone health become part of the integral management of persons with MS.

  18. Regulatory multitasking of tolerogenic dendritic cells – lessons taken from Vitamin D3-treated tolerogenic dendritic cells

    Directory of Open Access Journals (Sweden)

    Tatjana eNikolic

    2013-05-01

    Full Text Available Tolerogenic dendritic cells (DCs work through silencing of differentiated antigen-specific T cells, activation and expansion of naturally occurring T regulatory cells (Tregs, transfer of regulatory properties to T cells and the differentiation of naïve T cells into Tregs. Due to an operational definition based on T cell activation assays, the identity of tolerogenic DCs has been a matter of debate and it need not represent a specialized DC subset. Human tolerogenic DCs generated in vitro using inhibitory cytokines, growth factors, natural immunomodulators or genetic manipulation have been effective and several of these tolerogenic DCs are currently being tested for clinical use. Ex vivo generated tolerogenic DCs reduce activation of naïve T cells using various means, promote a variety of regulatory T cells and most importantly, frequently show stable inhibitory phenotypes upon repetitive maturation with inflammatory factors. Yet, tolerogenic DCs differ with respect to the phenotype or the number of regulatory mechanisms they employ to modulate the immune system. In our experience, tolerogenic DCs generated using the biologically active form of vitamin D (VD3-DCs, alone or combined with dexamethasone are proficient in their immunoregulatory functions. These tolerogenic DCs show a stable maturation-resistant semi-mature phenotype with low expression of activating co-stimulatory molecules, no production of the IL-12 family of cytokines and high expression of inhibitory molecules and IL-10. VD3-DCs induce increased apoptosis of effector T cells and induce antigen-specific regulatory T cells, which work through linked suppression ensuring infectious tolerance. Lessons learned on VD3-DCs help understanding the contribution of different pattern recognition receptors (PRRs and secondary signals to the tolerogenic function and how a cross-talk between DCs and T cells translates into immune regulation.

  19. Short-term vitamin D3 supplementation lowers plasma renin activity in patients with stable chronic heart failure: an open-label, blinded end point, randomized prospective trial (VitD-CHF trial).

    Science.gov (United States)

    Schroten, Nicolas F; Ruifrok, Willem P T; Kleijn, Lennaert; Dokter, Martin M; Silljé, Herman H; Lambers Heerspink, Hiddo J; Bakker, Stephan J L; Kema, Ido P; van Gilst, Wiek H; van Veldhuisen, Dirk J; Hillege, Hans L; de Boer, Rudolf A

    2013-08-01

    Many chronic heart failure (CHF) patients have low vitamin D (VitD) and high plasma renin activity (PRA), which are both associated with poor prognosis. Vitamin D may inhibit renin transcription and lower PRA. We investigated whether vitamin D3 (VitD3) supplementation lowers PRA in CHF patients. We conducted a single-center, open-label, blinded end point trial in 101 stable CHF patients with reduced left ventricular ejection fraction. Patients were randomized to 6 weeks of 2,000 IU oral VitD3 daily or control. At baseline, mean age was 64 ± 10 years, 93% male, left ventricular ejection fraction 35% ± 8%, and 56% had VitD deficiency. The geometric mean (95% CI) of 25-hydroxyvitamin D3 increased from 48 nmol/L (43-54) at baseline to 80 nmol/L (75-87) after 6 weeks in the VitD3 treatment group and decreased from 47 nmol/L (42-53) to 44 nmol/L (39-49) in the control group (P CHF patients had VitD deficiency and high PRA levels. Six weeks of supplementation with 2,000 IU VitD3 increased 25-hydroxyvitamin D3 levels and decreased PRA and plasma renin concentration. Copyright © 2013 Mosby, Inc. All rights reserved.

  20. Real-life use of vitamin D3-fortified bread and milk during a winter season: the effects of CYP2R1 and GC genes on 25-hydroxyvitamin D concentrations in Danish families, the VitmaD study

    DEFF Research Database (Denmark)

    Nissen, Ioanna; Vogel, Ulla Birgitte; Ravn-Haren, Gitte

    2014-01-01

    Common genetic variants rs10741657 and rs10766197 in CYP2R1 and rs4588 and rs842999 in GC and a combined genetic risk score (GRS) of these four variants influence late summer 25-hydroxyvitamin D (25(OH)D) concentrations. The objectives were to identify those who are most at risk of developing low...... vitamin D status during winter and to assess whether vitamin D3-fortified bread and milk will increase 25(OH)D concentrations in those with genetically determined low 25(OH)D concentrations at late summer. We used data from the VitmaD study. Participants were allocated to either vitamin D3-fortified bread...... 25(OH)D concentrations and carriage of 0-8 risk alleles (p vitamin D intake and the increase in 25(OH)D concentrations among carriers of 0...

  1. Vitamin D(3) at 50x AI attenuates the decline in paw grip endurance, but not disease outcomes, in the G93A mouse model of ALS, and is toxic in females.

    Science.gov (United States)

    Gianforcaro, Alexandro; Solomon, Jesse A; Hamadeh, Mazen J

    2013-01-01

    We previously demonstrated that dietary vitamin D(3) at 10x the adequate intake (AI) attenuates the decline in functional capacity in the G93A mouse model of ALS. We hypothesized that higher doses would elicit more robust changes in functional and disease outcomes. To determine the effects of dietary vitamin D(3) at 50xAI on functional outcomes (motor performance, paw grip endurance) and disease severity (clinical score), as well as disease onset, disease progression and lifespan in the transgenic G93A mouse model of ALS. Starting at age 25 d, 100 G93A mice (55 M, 45 F) were provided ad libitum with either an adequate (AI; 1 IU D(3)/g feed) or high (HiD; 50 IU D(3)/g feed) vitamin D(3) diet. HiD females consumed 9% less food corrected for body weight vs. AI females (P = 0.010). HiD mice had a 12% greater paw grip endurance over time between age 60-141 d (P = 0.015), and a 37% greater score during disease progression (P = 0.042) vs. AI mice. Although HiD females had a non-significant 31% greater CS prior to disease onset vs. AI females, they exhibited a significant 20% greater paw grip endurance AUC (P = 0.020) when corrected for clinical score. Dietary D(3) supplementation at 50x the adequate intake attenuated the decline in paw grip endurance, but did not influence age at disease onset, hindlimb paralysis or endpoint in the transgenic G93A mouse model of ALS. Furthermore, females may have reached the threshold for vitamin D(3) toxicity as evidence by reduced food intake and greater disease severity prior to disease onset.

  2. Safety and Efficacy of Banaba-Moringa oleifera-Green Coffee Bean Extracts and Vitamin D3 in a Sustained Release Weight Management Supplement.

    Science.gov (United States)

    Stohs, Sidney J; Kaats, Gilbert R; Preuss, Harry G

    2016-04-01

    This 60-day, 30-subject pilot study examined a novel combination of ingredients in a unique sustained release (Carbopol matrix) tablet consumed twice daily. The product was composed of extracts of banaba leaf, green coffee bean, and Moringa oleifera leaf and vitamin D3. Safety was assessed using a 45-measurement blood chemistry panel, an 86-item self-reported Quality of Life Inventory, bone mineral density, and cardiovascular changes. Efficacy was assessed by calculating a body composition improvement index (BCI) based on changes in dual energy X-ray absorptiometry measured fat mass (FM) and fat-free mass (FFM) as well as between the study group (SG) and a historical placebo group. No changes occurred in any blood chemistry measurements. Positive changes were found in the Quality of Life (QOL) inventory composite scores. No adverse effects were observed. Decreases occurred in FM (p = 0.004) and increases in FFM (p = 0.009). Relative to the historical placebo group, the SG lost more FM (p negative BCI of -2.7 lb. compared with a positive BCI in the SG of 3.4 lb., a 6.1 discordance (p = 0.0009). The data support the safety and efficacy of this unique product and demonstrate importance of using changes in body composition versus scale weight and BMI. © 2016 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd.

  3. Vitamin D3-Supplemented Yogurt Drink Improves Insulin Resistance and Lipid Profiles in Women with Gestational Diabetes Mellitus: A Randomized Double Blinded Clinical Trial.

    Science.gov (United States)

    Li, Qin; Xing, Baoheng

    2016-01-01

    Our study aimed to examine the effects of daily consumption of vitamin D3-supplemented yogurt (VDY) drink on insulin resistance and lipid profiles in pregnant gestational diabetes mellitus (GDM) patients. Participants aged 24-32 years in their second trimester were randomly assigned to consume either plain yogurt or VDY daily for 16 weeks. Metabolic and lipid profiles including levels of fasting plasma glucose (FPG), serum insulin, triacylglycerol (TAG), total cholesterol (TC) and low-density lipoprotein (LDL) were assessed at baseline (week 0) and end of trial (week 16). After 16 weeks of intervention, insulin-related variables including FPG and serum insulin levels were markedly lower in VDY group participants. Insulin resistance parameters, such as homeostasis model of assessment of insulin resistance and β cell function, were also significantly reduced in VDY group participants. Moreover, levels of TAG, TC and LDL, as well as the TC to high-density lipoprotein ratio, had also significantly decreased in the VDY group. Daily consumption of VDY drink improves insulin resistance and lipid profiles in women with GDM. © 2016 S. Karger AG, Basel.

  4. Development of a validated UPLC method for simultaneous estimation of both free and entrapped (in solid lipid nanoparticles) all-trans retinoic acid and cholecalciferol (vitamin D3) and its pharmacokinetic applicability in rats.

    Science.gov (United States)

    Kumar, Manoj; Sharma, Gaurav; Singla, Dinesh; Singh, Sukhjeet; Sahwney, Sudhir; Chauhan, Anurag S; Singh, Gagandeep; Kaur, Indu Pal

    2014-03-01

    A sensitive ultra-performance liquid chromatography (UPLC) method was developed for simultaneous estimation of all-trans retinoic acid (ATRA) and cholecalciferol (vitamin D3) in rat plasma. The method was validated over the linear range of 1.0-5000ng/ml (r(2)=0.999) for both vitamins with a limit of detection of 0.5ng/ml. Chromatographic separation was achieved using liquid-liquid extraction (LLE) on an Acquity BEH RP 18 column (2.1mm×50mm, I.D. 1.7μm), with mobile phase comprising of acetonitrile:methanol:water (90:8:2, v/v/v), at a flow rate of 0.20ml/min and a total run time of 5min. Intra and inter-day variability (RSD) was ≤3.1%, and the accuracy varied between 95.4-99.9% and 95.3-101.1% respectively, for ATRA and 98.5-100.8% and 99.3-101.7%, respectively for vitamin D3. High recovery of ≥96.0% for ATRA and ≥87.80% for vitamin D3 was achieved. ATRA and vitamin D3 were stable in plasma under different storage and processing conditions. The method was applied to estimate the total drug content and entrapment efficiency of ATRA and vitamin D3 loaded solid lipid nanoparticles (SLNs). Concentration of these two agents was determined in rat plasma after simultaneous subcutaneous administration in free form or when loaded into SLNs thus establishing pharmacokinetic application of the developed procedure. Results indicated an improvement in AUC0-∞ by 5.4 times and 29.4 times for ATRA and vitamin D3, respectively, upon their incorporation into SLNs. Simultaneous administration of these two vitamins and their improved and prolonged bioavailability has scope for their use in treatment and control of tuberculosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Efeitos do Ácido L-Glutâmico e da Vitamina D3 nos Fêmures e Tibiotarsos de Pintos de Corte Effects of L-Glutamic Acid and Vitamin D3 on Femur and Tibiotarsus of Broiler Chicks

    Directory of Open Access Journals (Sweden)

    Fernanda Alvares da Silva

    2001-12-01

    Full Text Available Um experimento foi conduzido com o objetivo de estudar os efeitos de três níveis (5, 10 e 15% de ácido L-glutâmico (L-Glu e quatro níveis (0, 5000, 10.000 e 15.000 UI/kg de vitamina D3 (VD nos parâmetros ósseos de pintos de corte machos, Hubbard. Os animais foram criados em baterias aquecidas e alimentados, à vontade, com dietas de aminoácidos purificados de 1 a 14 dias de idade. O experimento foi realizado em esquema fatorial, em delineamento inteiramente casualizado 3 x 4, com quatro repetições de sete aves cada. Observaram-se comprimentos máximos (37,61 e 50,36 mm, com 9,51% de L-Glu e 15.000 UI de VD e 9,99% de L-Glu e 15.000 UI de VD, para o fêmur e tibiotarso, respectivamente. O diâmetro do fêmur (3,62 mm e tibiotarso (3,17 mm aumentou até o nível máximo estimado, de 10,49% de L-Glu e 15.000 UI de VD, e 11,04% de L-Glu e 15.000 UI de VD, respectivamente. A resistência máxima estimada para o fêmur (52,47 kgf/mm foi determinada com 7,57% de L-Glu e 8.978 UI, e a do tibiotarso (43,35 kgf/mm com 6,24% de L-Glu e 12.591 UI de VD. Não foi observado efeito de tratamento nas concentrações de proteínas colagenosas (PC no fêmur, que foi constante e igual a 23,44 mg/100 g. As menores concentrações de proteínas não-colagenosas (PNC (2,5 mg/100 g e 2,15 mg/100 g foram obtidas com 9,32% e 9,73% de L-Glu, no fêmur e tibiotarso, respectivamente. As maiores concentrações de proteínas totais (PT no fêmur e tibiotarso foram de 30,04 mg/100 g e 30,03 mg/100 g. As aves alimentadas com 10% de L-Glu apresentaram adequado desenvolvimento dos ossos, baixas concentrações de PNC nos ossos e menor incidência de problemas de pernas.An experiment was conducted to study the effects of three levels (5, 10 and 15% of L-Glutamic Acid (L-Glu and four levels (0, 5000, 10,000 and 15,000 IU/kg of diet of vitamin D3 (VD on bone parameters of 14 days male broilers, Hubbard. They were fed purified amino acid diets and reared in electrically

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

    Science.gov (United States)

    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...

  7. Common variants in CYP2R1 and GC genes are both determinants of serum 25-hydroxyvitamin D concentrations after UVB irradiation and after consumption of vitamin D3-fortified bread and milk during winter in Denmark

    DEFF Research Database (Denmark)

    Nissen, Ioanna; Vogel, Ulla; Ravn-Haren, Gitte

    2014-01-01

    Background: Little is known about how the genetic variation in vitamin D modulating genes influences ultraviolet (UV)B–induced 25-hydroxyvitamin D [25(OH)D] concentrations. In the Food with vitamin D (VitmaD) study, we showed that common genetic variants rs10741657 and rs10766197 in 25-hydroxylase...... or 7.5 standard erythema doses during a 10-d period in winter. The VitmaD study included 201 healthy Danish families who were given vitamin D3–fortified bread and milk or placebo for 6 mo during the winter. Results: After UVB treatments, rs10741657 in CYP2R1 and rs4588 in GC predicted UVB-induced 25(OH...

  8. The Effect of Vitamin D3 Alone and Mixed with IFN-γ on Tachyzoites of Toxoplasma Gondii (RH Strain Proliferation and Nitric Oxide (NO Production in Infected Macrophages of BALB/C Mice

    Directory of Open Access Journals (Sweden)

    E Al-Kawaz

    2010-09-01

    Full Text Available Introduction: Toxoplasma gondii is an obligatory interacelullar parasite that infects nucleated cells in its intermediate hosts. The aim of the present study was to determine the effect of vitamin D3 on the multiplication of T. gondii in peritoneal macrophage of Balb/c mice and nitric oxide production by macrophages. Methods: According to usage of vitamin D3 (one dose or seven doses and INFγ in vitro and in vivo, this study was divided into four experiments. In all experiments, the macrophages were col­lected from peritoneum and cultured in RPMI-1640. Then the supernatants were collected after 24 h and their nitric oxide was measure. After 96 h, the macrophages were collected and stained and the number of tachyzoites was measured. Results: The first experiment (the mice were infected with tachyzoites and after 2 h, got one dose vita­min D3 intraperitonealy showed the best results. The mean of tachyzoites per macrophages was 2.37, and mean ± SD of nitric oxide was 187.8 ± 9.Discussion: High-level production of nitric oxide may be related to the only one injection of vita­min D3. The injection in long time might suppress the immune system.

  9. The effect of combined resistance exercise training and vitamin D3 supplementation on musculoskeletal health and function in older adults: a systematic review and meta-analysis

    National Research Council Canada - National Science Library

    Anneka Elizabeth Antoniak; Carolyn A Greig

    2017-01-01

    .... There is evidence that both exercise training and vitamin D supplementation may benefit musculoskeletal health in older adults, and it is plausible that in combination their effects may be additive...

  10. Novel regulation of 25-hydroxyvitamin D3 24-hydroxylase (24(OH)ase) transcription by glucocorticoids: cooperative effects of the glucocorticoid receptor, C/EBP beta, and the Vitamin D receptor in 24(OH)ase transcription.

    Science.gov (United States)

    Dhawan, Puneet; Christakos, Sylvia

    2010-08-15

    Glucocorticoid-induced bone loss has been proposed to involve direct effects on bone cells as well as alterations in calcium absorption and excretion. Since vitamin D is important for the maintenance of calcium homeostasis, in the present study the effects of glucocorticoids on vitamin D metabolism through the expression of 24(OH)ase, an enzyme involved in the catabolism of 1,25(OH)(2)D(3), were examined. Injection of vitamin D replete mice with dexamethasone (dex) resulted in a significant induction in 24(OH)ase mRNA in kidney, indicating a regulatory effect of glucocorticoids on vitamin D metabolism. Whether glucocorticoids can affect 24(OH)ase transcription is not known. Here we demonstrate for the first time a glucocorticoid receptor (GR) dependent enhancement of 1,25(OH)(2)D(3)-induced 24(OH)ase transcription. Dex treatment of GR and vitamin D receptor (VDR) transfected COS-7 cells and dex treatment of osteoblastic cells (in which VDR and GR are present endogenously) potentiated 1,25(OH)(2)D(3)-induced 24(OH)ase transcription. In addition, GR was found to cooperate with C/EBP beta to enhance VDR-mediated 24(OH)ase transcription. Using the rat 24(OH)ase promoter with the C/EBP site mutated, GR-mediated potentiation of 1,25(OH)(2)D(3)-induced 24(OH)ase transcription was inhibited. Immunoprecipitation indicated that that GR can interact with C/EBP beta and ChIP/re-ChIP analysis showed that C/EBP beta and GR bind simultaneously to the 24(OH)ase promoter. These findings indicate a novel mechanism whereby glucocorticoids can alter VDR-mediated 24(OH)ase transcription through functional cooperation between C/EBP beta and GR that results in an enhanced ability of C/EBP beta to cooperate with VDR in the regulation of 24(OH)ase. (c) 2010 Wiley-Liss, Inc.

  11. Moderate Amounts of Vitamin D3 in Supplements are Effective in Raising Serum 25-Hydroxyvitamin D from Low Baseline Levels in Adults: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Susan J Whiting

    2015-04-01

    Full Text Available There is controversy surrounding the designation of vitamin D adequacy as defined by circulating levels of the metabolite 25-hydroxyvitamin D (25(OHD. Depending on the cutoff level chosen, dietary intakes of vitamin D may or may not provide sufficient impact upon vitamin D status measured as improvement in serum levels of 25(OHD. We sought to examine whether modest daily doses (5–20 μg as found in fortified foods or multivitamin supplements had a measureable impact on vitamin D status, defined as moving from below to above 50 nmol/L, or from less than 30 nmol/L to above 30 nmol/L. Published literature was searched for relevant articles describing randomized controlled trials. Exclusion criteria were: studies not involving humans; review articles; studies lacking blood level data pre- and post-treatment; no control group; bolus treatments (weekly, monthly, yearly; vitamin D <5 μg or >20 μg; baseline 25(OHD ≥75 nmol/L; subjects not defined as healthy; studies <8 weeks; and age <19 years. Of the 127 studies retrieved, 18 publications with 25 separate comparisons met criteria. The mean rate constant, defined as change in 25(OHD in nmol/L per μg vitamin D administered, was calculated as 2.19 ± 0.97 nmol/L per μg. There was a significant negative correlation (r = −0.65, p = 0.0004 between rate constant and administered dose. To determine impact of the dose reflecting the Estimated Average Requirement (EAR of 10 μg administered in nine studies (10 comparisons, in every case mean 25(OHD status rose either from “insufficient” (30–50 nmol/L to “sufficient” (>50 nmol/L or from “deficient” (<30 nmol/L to “insufficient” (>30 but <50 nmol/L. Our study shows that when baseline levels of groups were <75 nmol/L, for every microgram of vitamin D provided, 25(OHD levels can be raised by 2 nmol/L; and further, when groups were deficient or insufficient in vitamin D, there was significant value in providing additional 10 μg per day of

  12. Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial

    Science.gov (United States)

    Objective: To determine the effect of vitamin D (VITD) supplementation on tubular reabsorption of phosphate (TRP), serum parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and C telopeptide (CTX) in HIV-infected youth receiving and not receiving tenofovir-containing cART (TDF). Design: Ra...

  13. Vitamin D3 influence the Th1/Th2 ratio in C57BL/6 induced model of experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Maryam Soleimani

    2014-10-01

    Results: By using ELISA and RT-PCR the brain level of TNF-α, IL-10, IL-4 and IL-12 determined. Significant decrease of clinical symptoms in trial group which received vitamin D was seen comparing to control animals (P

  14. PENGARUH PEMBERIAN VITAMIN D3 (CALCITRIOL TERHADAP KADAR TGF β1 DAN IL-6 PADA PASIEN PENYAKIT GINJAL KRONIK STADIUM V

    Directory of Open Access Journals (Sweden)

    Rahma Anindita

    2017-06-01

    Full Text Available Penyebab utama morbiditas dan mortalitas pada pasien PGK adalah insiden kardiovaskuler yang didasari oleh proses aterosklerosis. Penurunan kadar TGF-β1 dan IL-6 dengan kalsifikasi vaskuler yang selanjutnya berkembang menjadi plak arteriosklerotik. Vitamin D menekan pada jalur aktivasi NF-ĸB sehingga mempunyai sifat anti inflamasi. Penelitian ini bertujuan untuk mengetahui pengaruh suplementasi vitamin D terhadap kadar TGF-β1 dan IL-6 pada pasien penyakit ginjal kronik stadium v yang menjalani hemodialisis. Penelitian ini merupakan penelitianeksperimen dengan randomisasi, sampel 30 orang, dibagi menjadi kelompok kontrol diberikan plasebo dan perlakuan diberikan calcitriol 1x0,5 μg peroral selama 4 minggu. Analisis statistik menggunakan SPSS 22for windows. Karakteristik penelitian yang berupa variabel kualitatif, uji homogenitas dilakukan menggunakan uji Chi Square. Uji beda dua rerata menggunakan uji t dengan signifikansi p <0,05. Hasil penelitian menunjukkan pemberian calcitriol 1x0,5 μg peroral jika dibandingkan placebo secara bermakna menurunkan kadarTGF-β1 (-1672,64±4217,61vs 7539,95±6435,86; p = 0,001, dan menurunkan kadar IL-6(- 1,45±3,14vs 4,20±2,83; p = 0,001. Pemberian suplementasi vitamin D dapat menurunkan kadar TGF-β1 dan menurunkan kadar IL-6 pada pasien penyakit ginjal kronik stadium V yang menjalani hemodialisis   Kata kunci: Vitamin D, TGF-β1, IL-6, Penyakit Ginjal Kronis

  15. Gene expression profiles in human and mouse primary cells provide new insights into the differential actions of vitamin D3 metabolites

    DEFF Research Database (Denmark)

    Tuohimaa, Pentti; Wang, Jing-Huan; Khan, Sofia

    2013-01-01

    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...... 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...

  16. Ceramide-induced TCR up-regulation

    DEFF Research Database (Denmark)

    Menné, C; Lauritsen, Jens Peter Holst; Dietrich, J

    2000-01-01

    inhibitors indicated that ceramide-induced TCR up-regulation was most probably mediated by serine/threonine protein phosphatase 2A. Analyses of T cell variants demonstrated that TCR up-regulation was dependent on the presence of an intact CD3gamma L-based motif and thus acted on TCR engaged in the recycling......The TCR is a constitutively recycling receptor meaning that a constant fraction of TCR from the plasma membrane is transported inside the cell at the same time as a constant fraction of TCR from the intracellular pool is transported to the plasma membrane. TCR recycling is affected by protein...... kinase C activity. Thus, an increase in protein kinase C activity affects TCR recycling kinetics leading to a new TCR equilibrium with a reduced level of TCR expressed at the T cell surface. Down-regulation of TCR expression compromises T cell activation. Conversely, TCR up-regulation is expected...

  17. Determination of vitamins D2 and D3 in selected food matrices by online high-performance liquid chromatography-gas chromatography-mass spectrometry (HPLC-GC-MS).

    Science.gov (United States)

    Nestola, Marco; Thellmann, Andrea

    2015-01-01

    An online normal-phase liquid chromatography-gas chromatography-mass spectrometry (HPLC-GC-MS) method was developed for the determination of vitamins D2 and D3 in selected food matrices. Transfer of the sample from HPLC to GC was realized by large volume on-column injection; detection was performed with a time-of-flight mass spectrometer (TOF-MS). Typical GC problems in the determination of vitamin D such as sample degradation or sensitivity issues, previously reported in the literature, were not observed. Determination of total vitamin D content was done by quantitation of its pyro isomer based on an isotopically labelled internal standard (ISTD). Extracted ion traces of analyte and ISTD showed cross-contribution, but non-linearity of the calibration curve was not determined inside the chosen calibration range by selection of appropriate quantifier ions. Absolute limits of detection (LOD) and quantitation (LOQ) for vitamins D2 and D3 were calculated as approximately 50 and 150 pg, respectively. Repeatability with internal standard correction was below 2 %. Good agreement between quantitative results of an established high-performance liquid chromatography with UV detection (HPLC-UV) method and HPLC-GC-MS was found. Sterol-enriched margarine was subjected to HPLC-GC-MS and HPLC-MS/MS for comparison, because HPLC-UV showed strong matrix interferences. HPLC-GC-MS produced comparable results with less manual sample cleanup. In summary, online hyphenation of HPLC and GC allowed a minimization in manual sample preparation with an increase of sample throughput.

  18. Administration of vitamin D 3 induces CNPase and myelin oligodendrocyte glycoprotein expression in the cerebral cortex of the murine model of cuprizone-induced demyelination

    Directory of Open Access Journals (Sweden)

    Farhad Mashayekhi

    2016-10-01

    Full Text Available In the central nervous system (CNS the main proteins of myelin are proteolipid protein (PLP, myelin basic protein (MBP, myelin oligodendrocyte glycoprotein (MOG and CNPase. Myelin oligodendrocyte glycoprotein is a minor component of the myelin sheath, but is an important autoantigen linked to the pathogenesis of multiple sclerosis (MS. CNPase is expressed exclusively by oligodendrocytes in the CNS, and the appearance of CNPase seems to be one of the earliest events of oligodendrocyte differentiation and myelination. In this study the effects of vitamin D on total protein concentration, CNPase and MOG expression in the cerebral cortex of the murine model of cuprizone-induced demyelination was investigated. The mice were treated by cuprizone for five weeks in order to induce demyelination. The mice were then divided into 3 groups. The first group was injected intraperitoneally (IP with vitamin D diluted in olive oil in the amount of 5 µg/kg/daily body weight. The second group (SHAM was injected IP with olive oil and the third group was left without any injection as the control group (n = 11 for each group. After five weeks the mice were killed and the cerebral cortex was collected and the expression of CNPase and MOG was studied by Western blot. Total protein concentration in the vitamin D injected, SHAM and control groups were 0.918 ± 0.003, 0917 ± 0.004 and 0.916 ± 0.004 g/l, respectively (p > 0.05. However, a significant increase in the MOG and CNPase expression was seen in vitamin D injected group as compared to SHAM and control groups. It is concluded that vitamin D plays a role in the process of remyelination by increasing MOG and CNPase expression in the cortex.

  19. Phenylbutyrate Is Bacteriostatic against Mycobacterium tuberculosis and Regulates the Macrophage Response to Infection, Synergistically with 25-Hydroxy-Vitamin D3.

    Directory of Open Access Journals (Sweden)

    Anna K Coussens

    2015-07-01

    Full Text Available Adjunctive vitamin D treatment for pulmonary tuberculosis enhances resolution of inflammation but has modest effects on bacterial clearance. Sodium 4-phenylbutyrate (PBA is in clinical use for a range of conditions and has been shown to synergise with vitamin D metabolites to upregulate cathelicidin antimicrobial peptide (CAMP expression. We investigated whether clinically attainable plasma concentrations of PBA (0.4-4 mM directly affect Mycobacterium tuberculosis (Mtb growth and human macrophage and PBMC response to infection. We also tested the ability of PBA to enhance the immunomodulatory actions of the vitamin D metabolite 25(OHD3 during infection and synergistically inhibit intracellular Mtb growth. PBA inhibited Mtb growth in broth with an MIC99 of 1 mM, which was reduced to 0.25 mM by lowering pH. During human macrophage infection, PBA treatment restricted Mtb uptake, phagocytic receptor expression and intracellular growth in a dose-dependent manner. PBA independently regulated CCL chemokine secretion and induced expression of the antimicrobial LTF (lactoferrin, the anti-inflammatory PROC (protein C and multiple genes within the NLRP3 inflammasome pathway. PBA co-treatment with 25(OHD3 synergistically modulated expression of numerous vitamin D-response genes, including CAMP, CYP24A1, CXCL10 and IL-37. This synergistic effect was dependent on MAPK signalling, while the effect of PBA on LTF, PROC and NLRP3 was MAPK-independent. During PBA and 25(OHD3 co-treatment of human macrophages, in the absence of exogenous proteinase 3 (PR3 to activate cathelicidin, Mtb growth restriction was dominated by the effect of PBA, while the addition of PR3 enhanced growth restriction by 25(OHD3 and PBA co-treatment. This suggests that PBA augments vitamin D-mediated cathelicidin-dependent Mtb growth restriction by human macrophages and independently induces antimicrobial and anti-inflammatory action. Therefore through both host-directed and bacterial

  20. Differential gene expression by 1,25(OH)2D3in an endometriosis stromal cell line.

    Science.gov (United States)

    Ingles, Sue Ann; Wu, Liang; Liu, Benjamin T; Chen, Yibu; Wang, Chun-Yeh; Templeman, Claire; Brueggmann, Doerthe

    2017-10-01

    Endometriosis is a common female reproductive disease characterized by invasion of endometrial cells into other organs, frequently causing pelvic pain and infertility. Alterations of the vitamin D system have been linked to endometriosis incidence and severity. To shed light on the potential mechanism for these associations, we examined the effects of 1,25(OH) 2 D 3 on gene expression in endometriosis cells. Stromal cell lines derived from endometriosis tissue were treated with 1,25(OH) 2 D 3 , and RNA-seq was used to identify genes differentially expressed between treated and untreated cells. Gene ontology and pathway analyses were carried out using Partek Flow and Ingenuity software suites, respectively. We identified 1627 genes that were differentially expressed (886 down-regulated and 741 up-regulated) by 1,25(OH) 2 D 3 . Only one gene, CYP24A1, was strongly up-regulated (369-fold). Many genes were strongly down-regulated. 1,25(OH) 2 D 3 treatment down-regulated several genetic pathways related to neuroangiogenesis, cellular motility, and invasion, including pathways for axonal guidance, Rho GDP signaling, and matrix metalloprotease inhibition. These findings support a role for vitamin D in the pathophysiology of endometriosis, and provide new targets for investigation into possible causes and treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. The content of calcium and vitamin D3 in patients with morbid obesity before and after surgical treatment depending on the type of surgery

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    Ya.S. Bereznitsky

    2017-11-01

    Full Text Available Background. Obesity is the global problem of mankind. Overweight and obesity are among the five major risk factors for death. In the modern world, the problem of obesity is also discussed in the context of noncommunicable diseases, leading to significant difficulties for society. All obese patients are at risk of vitamin D deficiency and the development of secondary hyperparathyroidism, especially patients with morbid obesity. The purpose was to analyze the dynamics of changes in the levels of vitamin 25(OHD and calcium in patients with morbid obesity before and after biliopancreatic diversion (BPD in the modification of Hess-Marceau and sleeve gastrectomy. Materials and methods. Prospectively, 57 patients with morbid obesity and concomitant metabolic syndrome aged 21 to 62 years (mean age 40.00 ± 1.38 years were examined, they underwent surgery and were monitored at the surgical department 1 of the Dnepropetrovsk Medical Academy of Ministry of Health of Ukraine for 3 or more years after the operation. The distribution of patients in groups was carried out taking into account the applied method of surgical treatment. Clinical group 1 included 29 (50.9 % patients with BPD; group II — 28 (49.1 % patients with sleeve gastrectomy. In all patients, the levels of calcium and vitamin 25(OHD in the blood serum were determined. Evaluation of the study results was carried out in the dynamics of observation — at the first visit and within 3 years after surgery. Results. Analysis of the dynamics of morbid obesity after surgical treatment showed general trends to a significant (from p 0.05. Conclusions. The established direct correlation between the levels of vitamin D and calcium in the blood serum of patients who underwent BPD with the length of the common loop testified to the effectiveness of the BPD technique developed during the study (increasing the length of the common loop up to 1 m, the application of which led to a decrease in disturbances of

  2. Efeito da vitamina D3 e 25-hidroxi-colecalciferol sobre o desempenho, o rendimento de carcaça e a morfologia intestinal de frangos de corte¹ Effect of vitamin D3 and 25-hidroxicholecalciferol on performance, carcass yield and intestinal morphology in broiler chickens

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    Jerônimo Ávito Gonçalves de Brito

    2010-12-01

    of vitamin D from two sources (vitamin D3 and 25-OHD3 on diets for broiler chickens raised in cages. It was used 1,500 line Cobb-700 male chicks at one day of age, housed in metal cages (100, with appliances and management fitted for bird raising. In each growing phase (starter, from 1 to 21 days; growing, from 22 to 38 days, and finishing, from 39 to 45 days, it was evaluated four levels (programs of vitamin D supplementation (20/16/10; 37.5/30/18.8; 87.5/70/43.8 and 137.5/110/68.8 mg/kg ration from two sources. The two additional treatments consisted of combination of the two sources (D3 + 25-OHD3 at different proportions (50+37.7/40+30/25+18.8 and 50+70/40+56/25+35 mg/kg ration for starter, growing and finishing phases, respectively. It was used a complete random experimental design, in a 2 × 4 + 2 (sources × levels + aditionals and 10 replicates per treatment. The diets were based on corn and soybean meal, with supplementation of phytase (500 ftu/kg, following the recommendations of the national tables of nutritional requirements of non-ruminant animals. The performance and carcass characteristics as well as the intestinal morphology of the birds were evaluated. Vitamin-D supplementation at the starter phase improved weight gain and feed conversion of the birds. Greater weight gain and feed intake at 45 days of age were observed for the group of birds of the additional treatment associations. Carcass yield increased with the use of 25-OHD3. When compared to the single supplementation of vitamin D sources, the additional treatments promoted more benefits for most of the evaluated characteristics. The addition of 25-OHD3 in rations containing vitamin D3 improves performance characteristics of broilers.

  3. Vitamins

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    Ruiz-Roso, Baltasar

    1998-08-01

    Full Text Available A thermal treatment is an intrinsic part of most food processing procedures and may be employed to inactive enzimes and toxic '• factors, to change texture and flavour or to preserve. The vitamin degree of transformation or destruction in cooking methods depends on the temperature and on the time of exposure to this temperature. Oxigen, light and transition metals frequently play an active role in accelerating or promoting vitamin losses. Both chemical change and difussion proceed more rapidly as the temperature is raised. An advantage of deep frying consists of the fact that the temperature within the food does not exceed the temperature of the steam under the crust, and that frying times are in general very short compared to other cooking procedures. Another advantages may be the low content of dissolved oxygen in frying fats, and also in its high tocopherol content. There is no leaching of water-soluble vitamins in deep-frying. Speaking of vitamin stability we have to keep in mind that the concept of vitamins is a more physiological concept than a chemical one. The stability itself is not a property of the various vitamins but rather of the various chemical compounds sometimes called vitamers, of which a certain vitamin group consists. For practical purposes, vitamin losses should be considered only in foods wich substantially contribute to the vitamin supply of single people or population groups. There is little data in the literature about vitamin changes in deep-frying of food. However published experimental data on vitamin loses show that deep-frying is one of the most protective cooking procedures. For example, in ours results the vitamin C losses of stewed vegetable foods were twice higher than that of fried ones, (raw potatoes containing 19 mg/100g fresh weight, 13 mg/100 fried in olive oil, and 5 mg/100g stewed in the same oil.

  4. Effects of Chronic Vitamin D3 Hormone Administration on Anxiety-Like Behavior in Adult Female Rats after Long-Term Ovariectomy

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    Julia Fedotova

    2017-01-01

    Full Text Available The present preclinical study was created to determine the therapeutic effects of vitamin D hormone treatment as an adjunctive therapy alone or in a combination with low dose of 17β-estradiol (17β-E2 on anxiety-like behavior in female rats with long-term absence of estrogen. Accordingly, the aim of the current study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg subcutaneously, SC, once daily, for 14 days on the anxiety-like state after long-term ovariectomy in female rats. Twelve weeks postovariectomy, cholecalciferol was administered to ovariectomized (OVX rats and OVX rats treated with 17β-E2 (0.5 µg/rat SC, once daily, for 14 days. Anxiety-like behavior was assessed in the elevated plus maze (EPM and the light/dark test (LDT, and locomotor and grooming activities were tested in the open field test (OFT. Cholecalciferol at two doses of 1.0 and 2.5 mg/kg alone or in combination with 17β-E2 produced anxiolytic-like effects in OVX rats as evidenced in the EPM and the LDT, as well as increased grooming activity in the OFT. Our results indicate that cholecalciferol, at two doses of 1.0 and 2.5 mg/kg, has a profound anxiolytic-like effects in the experimental rat model of long-term estrogen deficiency.

  5. Predictive value of age and serum parathormone and vitamin d3 levels for postoperative hypocalcemia after total thyroidectomy for nontoxic multinodular goiter.

    Science.gov (United States)

    Erbil, Yesim; Bozbora, Alp; Ozbey, Nese; Issever, Halim; Aral, Feríhan; Ozarmagan, Selçuk; Tezelman, Serdar

    2007-12-01

    Age, postoperative serum parathormone (PTH) level, and preoperative serum 25-hydroxyvitamin D(3) (25-OHD) level predict postoperative hypocalcemia after total thyroidectomy. Prospective clinical trial. Tertiary referral center. One hundred thirty patients with nontoxic multinodular goiter. Patients were divided into 2 groups according to the postoperative serum calcium level. Group 1 (n = 32) consisted of patients with a postoperative serum calcium level of 8 mg/dL or less, and group 2 (n = 98) consisted of patients with a postoperative serum calcium level higher than 8 mg/dL. The preoperative serum 25-OHD level and preoperative and postoperative serum calcium and PTH levels were determined. The number of patients developing hypocalcemia and prediction of postoperative hypocalcemia by the serum 25-OHD and PTH levels. Hypocalcemia developed in 32 patients (24.6%) (group 1). The preoperative serum 25-OHD level and postoperative serum calcium and PTH levels in group 1 were significantly lower than in group 2 (P = .001). With logistic regression analysis, factors that were predictive of postoperative hypocalcemia included a preoperative serum 25-OHD level less than 15 ng/mL (P postoperative serum PTH level less than 10 pg/mL (P = .01; odds ratio, 16.4), and being older than 50 years (P = .01; odds ratio, 4.6). Age, a low preoperative serum 25-OHD level, and a low postoperative serum PTH level are significantly associated with postoperative hypocalcemia. The low preoperative serum 25-OHD level was more significant than the low postoperative serum PTH level in the prediction of postoperative hypocalcemia.

  6. 1,25-Dihydroxyvitamin-D3 Induces Avian β-Defensin Gene Expression in Chickens.

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    Long Zhang

    Full Text Available Host defense peptides (HDPs play a critical role in innate immunity. Specific modulation of endogenous HDP synthesis by dietary compounds has been regarded as a novel approach to boost immunity and disease resistance in animal production. 1,25-dihydroxy vitamin D3 (1,25D3 is well known as a powerful HDP inducer in humans, but limited information about the effect of 1,25D3 on HDPs in poultry is available. Here, we sought to examine whether 1,25D3 could stimulate avian β-defensin (AvBD expression in chickens. We used chicken embryo intestinal epithelial cells (CEIEPCs and peripheral blood mononuclear cells (PBMCs to study the effect of 1,25D3 on the expression of AvBDs. We observed that 1,25D3 is able to up-regulate the expression of several AvBDs in CEIEPCs and PBMCs, whereas it increased the amounts of AvBD4 mRNA in CEIEPCs only in the presence of lipopolysaccharide (LPS. On the other hand, LPS treatment not only inhibited the expression of CYP24A1 but also altered the expression pattern of VDR in CEIEPCs. Furthermore, AvBDs were not directly regulated by 1,25D3, as cycloheximide completely blocked 1,25D3-induced expression of AvBDs. Our observations suggest that 1,25D3 is capable of inducing AvBD gene expression and is a potential antibiotic alternative through augmentation of host innate immunity as well as disease control in chickens.

  7. Time course of 25(OHD3 vitamin D3 as well as PTH (parathyroid hormone during fracture healing of patients with normal and low bone mineral density (BMD

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    Wöfl Christoph

    2013-01-01

    Full Text Available Abstract Background Until now the exact biochemical processes during healing of metaphyseal fractures of healthy and osteoporotic bone remain unclear. Especially the physiological time courses of 25(OHD3 (Vitamin D as well as PTH (Parathyroid Hormone the most important modulators of calcium and bone homeostasis are not yet examined sufficiently. The purpose of this study was to focus on the time course of these parameters during fracture healing. Methods In the presented study, we analyse the time course of 25(OHD3 and PTH during fracture healing of low BMD level fractures versus normal BMD level fractures in a matched pair analysis. Between March 2007 and February 2009 30 patients older than 50 years of age who had suffered a metaphyseal fracture of the proximal humerus, the distal radius or the proximal femur were included in our study. Osteoporosis was verified by DEXA measuring. The time courses of 25(OHD3 and PTH were examined over an eight week period. Friedmann test, the Wilcoxon signed rank test and the Mann-Withney U test were used as post-hoc tests. A p-value ≤ 0.05 was considered significant. Results Serum levels of 25(OHD3 showed no differences in both groups. In the first phase of fracture healing PTH levels in the low BMD level group remained below those of the normal BMD group in absolute figures. Over all no significant differences between low BMD level bone and normal BMD level bone could be detected in our study. Conclusions The time course of 25(OHD3 and PTH during fracture healing of patients with normal and low bone mineral density were examined for the first time in humans in this setting and allowing molecular biological insights into fracture healing in metaphyseal bones on a molecural level. There were no significant differences between patients with normal and low BMD levels. Hence further studies will be necessary to obtain more detailed insight into fracture healing in order to provide reliable decision criteria for

  8. Tumor-produced versican V1 enhances hCAP18/LL-37 expression in macrophages through activation of TLR2 and vitamin D3 signaling to promote ovarian cancer progression in vitro.

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    Dong Li

    Full Text Available Tumor-associated macrophages have been shown to promote tumor growth. They may have an obligatory function in angiogenesis, invasion, and metastasis through release of inflammatory mediators. Their presence in ovarian cancer has been correlated with poor prognosis in these patients. The human cationic antimicrobial protein-18 (hCAP18/LL-37 was originally identified as an effector molecule of the innate immune system. It is released by innate immune cells, such as macrophages, to combat microorganisms. Previous studies have characterized the hCAP18/LL-37 as a growth factor that has been shown to promote ovarian tumor progression. However, the role hCAP18/LL-37 has in macrophage-promoted ovarian tumor development and how its expression is controlled in this context remains poorly understood. Here, we demonstrate in co-culture experiments of macrophages and ovarian cancer cells a significant increase in the in vitro proliferation and invasiveness of the tumor cells is observed. These enhanced growth and invasion properties correlated with hCAP18/LL-37 induction. HCAP18/LL-37 expression was diminished by addition of two neutralizing antibodies, TLR2 or TLR6, as well as Cyp27B1 or VDR inhibitors. Furthermore, either the TLR2 or TLR6 antibody reduced vitamin D3 signaling and tumor cell progression in vitro. Addition of Cyp27B1 or VDR inhibitors abrogated TLR2/6 activation-induced expression of hCAP18/LL-37 in macrophages. Knockdown of tumor-produced versican V1 by RNAi in these tumor cells led to a decreased induction of hCAP18/LL-37 in macrophages. Versican V1 knockdown also inhibited TLR2 and vitamin D3 signaling, as well as growth and invasiveness of these tumor cells in the in vitro co-culture. In summary, we have found that versican V1 enhances hCAP18/LL-37 expression in macrophages through activation of TLR2 and subsequent vitamin D-dependent mechanisms which promote ovarian tumor progression in vitro.

  9. Vitamin D Test

    Science.gov (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Vitamin D Tests Share this page: Was this page helpful? Also known as: Ergocalciferol (Vitamin D 2 ); Cholecalciferol (Vitamin D 3 ); Calcidiol (25- ...

  10. Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults with HIV Infection Being Treated with Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    Havens, Peter L; Stephensen, Charles B; Van Loan, Marta D; Schuster, Gertrud U; Woodhouse, Leslie R; Flynn, Patricia M; Gordon, Catherine M; Pan, Cynthia G; Rutledge, Brandy; Harris, D Robert; Price, Georgine; Baker, Alyne; Meyer, William A; Wilson, Craig M; Hazra, Rohan; Kapogiannis, Bill G; Mulligan, Kathleen

    2017-08-21

    Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized vitamin D3 (VITD3) would increase BMD in youth receiving TDF. Randomized double-blind placebo-controlled trial of directly observed VITD3 vs. placebo every 4 weeks for 48 weeks in youth ages 16-24 years with HIV, viral load <200 copies/mL, taking TDF-containing combination antiretroviral therapy (TDF-cART) for ≥180 days. Participants (N=214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg, plus monthly randomized VITD3 50,000 IU (N=109) or placebo (N=105). Outcome was change from baseline to week 48 in lumbar spine BMD (LSBMD). Data presented are median (Q1, Q3). Participants were age 22.0 (21.0, 23.0) years, 84% male, and 74% black/African American. At baseline 62% had 25-hydroxy vitamin D [25-OHD] <20 ng/mL. Multivitamin adherence was 49 (29, 69)%, and VITD3/placebo adherence 100 (100, 100)%. Vitamin D intake was 2020 (1914, 2168) and 284 (179, 394) IU/day, and serum 25-OHD concentration was 36.9 (30.5, 42.4) and 20.6 (14.4, 25.8) ng/mL at 48 weeks in VITD3 and placebo groups, respectively (P<0.001). From baseline to week 48, LSBMD increased by 1.15 (-0.75, 2.74)% in the VITD3 group (N=99; P<0.001) and 0.09 (-1.49, 2.61)% in the placebo group (N=89; P=0.25), without between-group difference (P=0.12). VITD3 group changes occurred with baseline 25-OHD <20 ng/mL (1.17 (-0.82, 2.90)%; P=0.004) and ≥20 ng/mL (0.93 (-0.26, 2.15)%; P=0.033). For youth taking TDF-cART, LSBMD increased through 48 weeks with VITD3 plus multivitamin, but not with placebo plus multivitamin, independent of baseline vitamin D status.

  11. Vitamins

    Science.gov (United States)

    ... fruits, like oranges cantaloupe strawberries tomatoes broccoli cabbage kiwi fruit sweet red peppers previous continue Vitamin D ... leafy green vegetables dairy products, like milk and yogurt broccoli soybean oil When your body gets this ...

  12. Vitamins

    Science.gov (United States)

    ... broccoli, Brussels sprouts, and asparagus) Dark leafy vegetables (spinach, kale, collards, and turnip greens) Fish, liver, beef, and eggs WATER-SOLUBLE VITAMINS Biotin: Chocolate Cereal Egg yolk Legumes ...

  13. Vitamin D Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... forms of vitamin D that are important for nutrition: vitamin D2 and vitamin D3. Vitamin D2 mainly comes ... from: http://www.merckmanuals.com/home/disorders-of-nutrition/vitamins/vitamin-d National Cancer Institute [Internet]. Bethesda (MD): ...

  14. 1, 25(OH)2D3 Inhibits Hepatocellular Carcinoma Development Through Reducing Secretion of Inflammatory Cytokines from Immunocytes

    Science.gov (United States)

    Guo, Jian; Ma, Zhenhua; Ma, Qingyong; Wu, Zheng; Fan, Ping; Zhou, Xiaojie; Chen, Lulu; Zhou, Shuang; Goltzman, David; Miao, Dengshun; Wu, Erxi

    2014-01-01

    Epidemiological and clinical studies have indicated that low vitamin D activity is not only associated with an increased cancer risk and a more aggressive tumor growth, but also connected with an aggravated liver damage caused by chronic inflammation. Meanwhile, increasing evidence has demonstrated that 1,25(OH)2D3 (the most biologically active metabolite of vitamin D) can inhibit inflammatory response in some chronic inflammatory associated cancer, which is considered to have the anti-tumor potency. However, the interaction between 1,25(OH)2D3 and inflammation during hepatocellular carcinoma (HCC) initiation and progression is not yet clear. Here, we report an anti-tumorigenesis effect of 1,25(OH)2D3 via decreasing inflammatory cytokine secretion in HCC and hypothesize the possible underlying mechanism. Firstly, we show that the enhanced tumor growth is associated with elevated inflammatory cytokine IL-6 and TNF-α in 1α(OH)ase gene-knockout mice. Secondly, 1,25(OH)2D3 can inhibit vitamin D receptor (VDR) shRNA interfered tumor cell growth through decreasing inflammatory cytokine secretion in vitro and in vivo. Finally, using p27kip1 gene knock-out mouse model, we demonstrate that the effect of 1,25(OH)2D3 in inhibiting immune cell related inflammatory cytokine secretion, exerts in a p27kip1 gene dependent way. Collectively, 1,25(OH)2D3 inhibits HCC development through up-regulating the expression of p27kip1 in immune cell and reducing inflammatory cytokine production. PMID:23992309

  15. Roles of 1,25(OH2D3 and Vitamin D Receptor in the Pathogenesis of Rheumatoid Arthritis and Systemic Lupus Erythematosus by Regulating the Activation of CD4+ T Cells and the PKCδ/ERK Signaling Pathway

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    Xiao-Jie He

    2016-12-01

    Full Text Available Background/Aims: The study aims to elucidate the roles of 1,25(OH2D3 and vitamin D receptor (VDR in the pathogenesis of rheumatoid arthritis (RA and systemic lupus erythematosus (SLE by regulating the activation of CD4+ T cells and the PKCδ/ERK signaling pathway. Methods: From January 2013 to December 2015, a total of 130 SLE patients, 137 RA patients and 130 healthy controls were selected in this study. Serum levels of 1,25(OH2D3 and VDR mRNA expression were detected by ELISA and real-time fluorescence quantitative PCR (RT-qPCR. Density gradient centrifugation was performed to separate peripheral blood mononuclear cells (PBMCs. CD4+ T cells were separated using magnetic activated cell sorting (MACS. CD4+T cells in logarithmic growth phase were collected and assigned into 9 groups: the normal control group, the normal negative control (NC group, the VDR siRNA group, the RA control group, the RA NC group, the VDR over-expressed RA group, the SLE control group, the SLE NC group, and the VDR over-expressed SLE group. The mRNA and protein expressions of VDR, PKCδ, ERK1/2, CD11a, CD70 and CD40L were detected by RT-qPCR and Western blotting. Bisulfite genomic sequencing was conducted to monitor the methylation status of CD11a, CD70 and CD40L. Results: Compared with healthy controls, serum 1,25(OH2D3 level and VDR mRNA expression in peripheral blood were decreased in SLE patients and RA patients. With the increase of concentrations of 1,25(OH2D3 treatment, the VDR mRNA expression and DNA methylation levels of CD11a, CD70 and CD40L were declined, while the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L were elevated in SLE, RA and normal CD4+T cells. Compared with the SLE contro, RA control, SLE NC and RA NC groups, the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L decreased but DNA methylation levels of CD11a, CD70 and CD40L increased in the VDR over-expressed SLE group and VDR over-expressed RA group. However, compared with the normal

  16. UV dependent vitamin D syntheses. UV exposure time balancing for optimum production of the vitamins D3 status in the human body. Final report; UV-abhaengige Vitamin D Synthese. Bilanzierung der Expositionszeit durch UV zur Produktion des optimalen Vitamin D{sub 3}-Bedarfes im menschlichen Koerper. Schlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Knuschke, P.; Lehmann, B.; Pueschel, A.; Roensch, H.

    2012-10-15

    UV-dependent vitamin D{sub 3} synthesis - balancing of UV exposure time and the production of an optimal vitamin D{sub 3} status in men The adverse health effects on human skin and eyes by UV radiation have been well known for years. They are known to the public, too. Increased exposures by the UV-B fraction of solar radiation cause e.g. sun burn as an acute skin reaction or an increased risk on skin cancer as a chronic effect. Radiation of the same spectral UV-B range is necessary to induce the essential vitamin D metabolism in men. The UV-induced vitamin D synthesis in the skin supplies the body with more than 90 % while our typical nutrition contributes no more than 10 %. These photobiological effects are diametrically opposed. Therefore, up to now there are contradictory recommendations to the public concerning the health effects of solar UV exposure. The aim of this research project was to evaluate the quantitative and qualitative relations of UV exposure and the vitamin D status in men taking into account different conditions in the population. In result, well-balanced recommendations on optimal UV exposures for the different fractions of the population should be elaborated, realizing health protection aspects against detrimental UV effects. A literature survey (updated in 2011) summarizes the current knowledge on the vitamin D metabolism, on the effects of the hormone vitamin D and on the stage of the current discussion on the optimal vitamin D status. In a number of studies of this project the effects of UV exposure on the vitamin D status (25OH-vitamin D{sub 3} und 1,25OH-vitamin D{sub 3}) were investigated. Exposure parameters were the photobiologically effective UV dose (with respect to the minimal erythema dose MED = individual sun burn dose in each investigated volunteer) and the extent of the exposed skin area: face and hands (like everyday conditions) or whole body respectively. Serial UV exposures were applied by natural solar UV radiation or by

  17. T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism.

    Science.gov (United States)

    Edfeldt, Kristina; Liu, Philip T; Chun, Rene; Fabri, Mario; Schenk, Mirjam; Wheelwright, Matthew; Keegan, Caroline; Krutzik, Stephan R; Adams, John S; Hewison, Martin; Modlin, Robert L

    2010-12-28

    We investigated the mechanisms by which T-cell cytokines are able to influence the Toll-like receptor (TLR)-induced, vitamin D-dependent antimicrobial pathway in human monocytes. T-cell cytokines differentially influenced TLR2/1-induced expression of the antimicrobial peptides cathelicidin and DEFB4, being up-regulated by IFN-γ, down-regulated by IL-4, and unaffected by IL-17. The Th1 cytokine IFN-γ up-regulated TLR2/1 induction of 25-hydroxyvitamin D-1α-hydroxylase (i.e., CYP27B1), leading to enhanced bioconversion of 25-hydroxyvitamin D(3) (25D(3)) to its active metabolite 1,25D(3). In contrast, the Th2 cytokine IL-4, by itself and in combination with the TLR2/1 ligand, induced catabolism of 25D(3) to the inactive metabolite 24,25D(3), and was dependent on expression of vitamin D-24-hydroxylase (i.e., CYP24A1). Therefore, the ability of T-cell cytokines to differentially control monocyte vitamin D metabolism represents a mechanism by which cell-mediated immune responses can regulate innate immune mechanisms to defend against microbial pathogens.

  18. Primary 1,25-dihydroxyvitamin D3 response of the interleukin 8 gene cluster in human monocyte- and macrophage-like cells.

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    Jussi Ryynänen

    Full Text Available Genome-wide analysis of vitamin D receptor (VDR binding sites in THP-1 human monocyte-like cells highlighted the interleukin 8 gene, also known as chemokine CXC motif ligand 8 (CXCL8. CXCL8 is a chemotactic cytokine with important functions during acute inflammation as well as in the context of various cancers. The nine genes of the CXCL cluster and the strong VDR binding site close to the CXCL8 gene are insulated from neighboring genes by CCCTC-binding factor (CTCF binding sites. Only CXCL8, CXCL6 and CXCL1 are expressed in THP-1 cells, but all three are up-regulated primary 1,25-dihydroxyvitamin D3 (1,25(OH2D3 target genes. Formaldehyde-assisted isolation of regulatory elements sequencing analysis of the whole CXCL cluster demonstrated 1,25(OH2D3-dependent chromatin opening exclusively for the VDR binding site. In differentiated THP-1 cells the CXCL8 gene showed a 33-fold higher basal expression, but is together with CXCL6 and CXCL1 still a primary 1,25(OH2D3 target under the control of the same genomic VDR binding site. In summary, both in undifferentiated and differentiated THP-1 cells the genes CXCL8, CXCL6 and CXCL1 are under the primary control of 1,25(OH2D3 and its receptor VDR. Our observation provides further evidence for the immune-related functions of vitamin D.

  19. Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal osteopenic women following a one-year double-blind RCT and on osteoblast-osteoclast co-cultures.

    Science.gov (United States)

    Maria, Sifat; Swanson, Mark H; Enderby, Larry T; D'Amico, Frank; Enderby, Brianna; Samsonraj, Rebekah M; Dudakovic, Amel; van Wijnen, Andre J; Witt-Enderby, Paula A

    2017-01-26

    This one-year double blind randomized control trial assessed the effects of nightly melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7; MSDK) on bone mineral density (BMD) and quality of life (QOL) in postmenopausal osteopenic women (ages 49-75). Compared to placebo, MSDK treatment increased BMD in lumbar spine (4.3%) and left femoral neck (2.2%), with an upward trend for total left hip (p=0.069). MSDK increased serum P1NP levels and reduced bone turnover (CTx:P1NP). Psychometric analyses indicated that mood and sleep quality improved for the MSDK group. MSDK-exposed human mesenchymal stem cells (hMSCs) and human peripheral blood monocytes (hPBMCs) plated in transwells or layered demonstrated increases in osteoblastogenesis, decreases in osteoclastogenesis, increases in OPG (TNFRSF11B) and decreases in RANKL (TNFSF11) levels. In transwell osteoblasts, MSDK increased pERK1/2 (MAPK1/MAPK3) and RUNX2 levels; decreased ERK5 (MAPK7); and did not affect the expression of NFκB (NFKB1) and β1integrin (ITGB1). In layered osteoblasts, MSDK also decreased expression of the metabolic proteins PPARγ (PPARG) and GLUT4 (SLC2A4). In adipose-derived human MSCs, MSDK induced osteoblastogenesis. These findings provide both clinical and mechanistic support for the use of MSDK for the prevention or treatment of osteopenia, osteoporosis or other bone-related diseases.

  20. Flow cytometry detection of vitamin D receptor changes during vitamin D treatment in Crohn's disease.

    Science.gov (United States)

    Bendix, M; Dige, A; Deleuran, B; Dahlerup, J F; Jørgensen, S P; Bartels, L E; Husted, L B; Harsløf, T; Langdahl, B; Agnholt, J

    2015-07-01

    Crohn's disease (CD) is a chronic inflammatory disease associated with a dysregulated T cell response towards intestinal microflora. Vitamin D has immune modulatory effects on T cells through the nuclear vitamin D receptor (VDR) in vitro. It is unclear how oral vitamin D treatment affects VDR expression. The aim of this study was to establish a flow cytometry protocol, including nuclear and cytoplasmic VDR expression, and to investigate the effects of vitamin D treatment on T cell VDR expression in CD patients. The flow cytometry protocol for VDR staining was developed using the human acute monocytic leukaemia cell line (THP-1). The protocol was evaluated in anti-CD3/CD28-stimulated peripheral blood mononuclear cells (PBMCs) from vitamin D3- (n = 9) and placebo-treated (n = 9) CD patients. Anti-VDR-stained PBMCs were examined by flow cytometry, and their cytokine production was determined by cytokine bead array. VDR, CYP27B1 and RXRα mRNA expression levels in CD4(+) T cells were measured by quantitative reverse transcriptase polymerase chain reaction. The flow cytometry protocol enabled detection of cytoplasmic and nuclear VDR expression. The results were confirmed by confocal microscopy and supported by correlation with VDR mRNA expression. VDR expression in CD4(+) T cells increased following stimulation. This VDR up-regulation was inhibited with 30% by vitamin D treatment compared to placebo in CD patients (P = 0027). VDR expression was correlated with in-vitro interferon-γ production in stimulated PBMCs (P = 0.01). Flow cytometry is a useful method with which to measure intracellular VDR expression. Vitamin D treatment in CD patients reduces T cell receptor-mediated VDR up-regulation. © 2015 British Society for Immunology.

  1. Association of T-regulatory cells and CD23/CD21 expression with vitamin D in children with asthma.

    Science.gov (United States)

    Chary, Anchoju Vijayendra; Hemalatha, Rajkumar; Murali, Machiraju Vasudeva; Jayaprakash, Dodle; Kumar, Bharathraj Dinesh

    2016-05-01

    Children with asthma have low vitamin D levels; however, we do not know whether low vitamin D is associated with impaired T-regulatory (Treg) cell population or high IgE receptors (CD23 and CD21) on B cells. To examine Treg cell function, CD23 and CD21 receptors, vitamin D, and vitamin D-regulating enzymes in children with asthma. Sixty children (2-6 years old) with asthma and 60 age-matched healthy children were selected as study participants. After collecting demographic and clinical data, blood samples were collected. Treg cells and CD23/CD21 expressions were evaluated by flow cytometry, 25-hydroxyvitamin D3 (25[OH]D3) was quantified by high-performance liquid chromatography, and cytokines and total IgE were estimated by enzyme-linked immunosorbent assay. Messenger RNA (mRNA) expressions of FOXP3, CD23, CD21, vitamin D receptors, and vitamin D-regulating enzymes were assessed by reverse transcription-polymerase chain reaction. The 25(OH)D3 concentrations and proportion of Treg cells were lower (P asthma. In contrast, the proportions of B cells with CD23 and CD21 expression were higher (P asthma compared with controls. Interleukin 10 and transforming growth factor β were also altered in asthma. The mRNA expression of CD23, CD21, and vitamin D receptors was up-regulated, whereas mRNA expression of vitamin D-regulating enzymes, CYP2R1, CYP27B1, and vitamin D binding protein (except CYP24A1) were up-regulated among children with asthma. The current study found impaired Treg cell population and high numbers of B cells with IgE receptors (CD23 and CD21) and altered regulatory cytokines in children with asthma, suggesting impaired immune regulation. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. 1α,25(OH)2D3Analog, MART-10, Inhibits Neuroendocrine Tumor Cell Metastasis After VEGF-A Stimulation.

    Science.gov (United States)

    Chiang, Kun-Chun; Yeh, Chun-Nan; Pang, Jong-Hwei S; Hsu, Jun-Te; Yeh, Ta-Sen; Chen, Li-Wei; Kuo, Sheng-Fong; Takano, Masashi; Chen, Tai C; Kittaka, Atsushi; Hsieh, Po-Jen; Juang, Horng-Heng

    2017-11-01

    Pancreatic neuroendocrine tumors (PanNETs) are usually diagnosed in an advanced stage. Most patients with PanNETs die of metastasis. Vascular endothelial growth factor-A (VEGF-A) is a strong stimulator of angiogenesis and tumor metastasis. We aimed to investigate the effect of MART-10 [19-nor-2α-(3-hydroxypropyl)-1α,25(OH) 2 D 3 ], a 1α,25-dihydroxy-vitamin D3 (1α,25(OH) 2 D 3 ) analog, on PanNET cell metastasis after VEGF-A stimulation. Migration and invasion assays, western blot, and immunofluorescent staining were applied in this study. VEGF-A increased PanNET cell migration and invasion, which was attenuated by 1α,25(OH) 2 D 3 and MART-10. VEGF-A treatment stimulated epithelial-mesenchymal transition (EMT) of PanNET cells. During this process, expression of snail family transcriptional repressor 1 and 2, and fibronectin was up-regulated. 1α,25(OH) 2 D 3 and MART-10 counteracted VEGF-A-induced EMT. In addition, expression of neuropilin 1, a key protein in VEGF-A signaling, was down-regulated by 1α,25(OH) 2 D 3 and MART-10. Furthermore, synthesis of F-actin was increased by VEGF-A and reduced by 1α,25(OH) 2 D 3 and MART-10. Our data indicate that MART-10 could be deemed a promising drug for PanNET treatment. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Using D3.js

    OpenAIRE

    Holloway, Keenan

    2017-01-01

    There's no escaping the fact that data visualization is hot right now. Everyone wants to tell their data's story visually, whether it be through a map, chart, or more detailed presentation. The difficulty is there are so many different tools that solve this, each one with their own benefits and limitations. D3.js is an awesome tool for handling this task -- which is the approach we've used for the sites like the Nation's Report Card, BlueCross BlueShield of North Carolina, GlobalChange, and o...

  4. Three-year follow-up of serum 25-hydroxyvitamin D, parathyroid hormone, and bone mineral density in nursing home residents who had received 12 months of daily bread fortification with 125 μg of vitamin D3

    Science.gov (United States)

    2013-01-01

    Background We conducted a single-arm clinical trial in institutionalized seniors, on the effects of high-dose vitamin D3-fortified bread daily intake (clinicaltrials.gov registration NCT00789503). Methods At 1 and 3 years after the dietary fortification was stopped, serum 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and bone mineral density were measured in 23 of the original study subjects, aged 60-82 years who had consumed bread buns (100 g) fortified with 320 mg elemental calcium and 125 μg (5,000 IU) vitamin D3 daily for one year. Results At the end of the 1-year supplementation phase (receiving vitamin D3 fortified bread daily), mean (SD) serum 25(OH)D was 127.3 ± 37.8 nmol/L (baseline for this follow-up). At 1-year follow-up, the serum 25(OH)D was 64.9 ± 24.8 nmol/L (p = 0.001, vs. baseline); and at 3-year follow-up it was 28.0 ± 15.0 nmol/L (p = 0.001 vs. baseline). Serum PTH was 18.8 ± 15.6 pg/ml at baseline while at Year 3 it was 48.4 ± 18.4 pg/ml (p = 0.001 vs. baseline). Lumbar spine BMD did not change from baseline to Year 3. However, by Year 3, hip BMD had decreased (0.927 ± 0.130 g/cm2 vs. 0.907 ± 0.121 g/cm2, p = 0.024). Conclusion Vitamin D nutritional status exhibits a long half-life in the body, and a true steady-state plateau may not even be reached 1 year after a discontinuation in dose. Furthermore, once the need for vitamin D has been established, based on a low baseline serum 25(OH)D concentrations, the appropriate action is to maintain corrective vitamin D supplementation over the long term. Trial registration Clinical trial registration number: NCT00789503 PMID:24120120

  5. Curcumin induces human cathelicidin antimicrobial peptide gene expression through a vitamin D receptor-independent pathway

    DEFF Research Database (Denmark)

    Guo, Chunxiao; Rosoha, Elena; Lowry, Malcolm B

    2013-01-01

    The vitamin D receptor (VDR) mediates the pleiotropic biologic effects of 1α,25 dihydroxy-vitamin D(3). Recent in vitro studies suggested that curcumin and polyunsaturated fatty acids (PUFAs) also bind to VDR with low affinity. As potential ligands for the VDR, we hypothesized that curcumin...... cancer cell line HT-29 and keratinocyte cell line HaCaT. We demonstrated that PUFAs failed to induce CAMP or CYP24A1 mRNA expression in all three cell lines, but curcumin up-regulated CAMP mRNA and protein levels in U937 cells. Curcumin treatment induced CAMP promoter activity from a luciferase reporter...... construct lacking the VDR binding site and did not increase binding of the VDR to the CAMP promoter as determined by chromatin immunoprecipitation assays. These findings indicate that induction of CAMP by curcumin occurs through a vitamin D receptor-independent manner. We conclude that PUFAs and curcumin do...

  6. Worldwide status of vitamin D nutrition

    NARCIS (Netherlands)

    Lips, P.T.A.M.

    2010-01-01

    The vitamin D status depends on the production of vitamin D3 in the skin under the influence of ultraviolet radiation and vitamin D intake through the diet or vitamin D supplements. The serum 25-hydroxyvitamin D (25(OH)D) concentration is the parameter of choice for the assessment of vitamin D

  7. Role of vitamin D derivatives in intestinal tissue of patients with inflammatory bowel diseases.

    Science.gov (United States)

    Martinesi, Maria; Ambrosini, Stefano; Treves, Cristina; Zuegel, Ulrich; Steinmeyer, Andreas; Vito, Annese; Milla, Monica; Bonanomi, Andrea G; Stio, Maria

    2014-09-01

    The adhesion molecule expression and matrix metalloproteinases (MMPs) are proposed to be major factors for intestinal injury mediated by T cells in (IBD) and are up-regulated in intestinal mucosa of IBD patients. To investigate the effect of vitamin D derivatives on adhesion molecules and MMPs in colonic biopsies of IBD patients. Biopsies from inflamed and non-inflamed tract of terminal ileum and colon and PBMC from the same IBD patients were cultured with or without vitamin D derivatives. MMP activity and adhesion molecule levels were determined. 1,25(OH)2D3 and ZK 191784 significantly decrease ICAM-1 protein levels in the biopsies obtained only from the inflamed region of intestine of UC patients, while MAdCAM-1 levels decrease in the presence of 1,25(OH)2D3 in the non-inflamed region, and, in the presence of ZK, in the inflamed one. In CD patients 1,25(OH)2D3 and ZK decrease ICAM-1 and MAdCAM-1 in the biopsies obtained from the non-inflamed and inflamed regions, with the exception of ICAM-1 in the inflamed region in the presence of 1,25(OH)2D3. The expression of MMP-9, MMP-2, and MMP-3 decreases in the presence of vitamin D derivatives in UC and CD with the exception of 1,25(OH)2D3 that does not affect the levels of MMP-9 and MMP-2 in CD. Vitamin D derivatives always affect MMP-9, MMP-2 and ICAM-1 in PBMC of UC and CD patients. Based on the increased expression of ICAM-1, MAdCAM-1 and MMP-2,-9,-3 in IBD, our study suggests that vitamin D derivatives may be effective in the management of these diseases. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  8. Vitamin D3 receptor ( VDR gene rs2228570 (Fok1 and rs731236 (Taq1 variants are not associated with the risk for multiple sclerosis: results of a new study and a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Elena García-Martín

    Full Text Available BACKGROUND: Some epidemiological, genetic, and experimental data suggest a possible role of vitamin D in the pathogenesis of multiple sclerosis (MS and in experimental autoimmune encephalomyelitis. Data on the possible contribution of several single nucleotide polymorphisms (SNP in the vitamin D receptor (VDR gene to the risk for MS are controversial. Several studies suggested an interaction between some SNPs in the VDR gene and HLADRB1*1501 in the risk for MS. OBJECTIVES: The aim of this study was to investigate a possible influence of the SNPs rs2228570 and rs731236 in the VDR gene in the risk for MS. A secondary objective was to address the possible interactions between VDR genes and HLADRB1*1501. METHODS: We analyzed the allelic and genotype frequency of VDR rs2228570, rs731236, and HLADRB1*1501 (rs3135388 in 303 patients with MS and 310 healthy controls, using TaqMan Assays. We also conducted a meta-analysis, that was carried out by using the software Meta-Disc 1.1.1 (http://www.hrc.es/investigacion/metadisc.html; Unit of Clinical Statistics, Hospital Ramón y Cajal, Madrid, Spain. Heterogeneity between studies in terms of degree of association was tested using the Q-statistic. RESULTS: VDR rs2228570 and rs731236 allelic and genotype frequencies did not differ significantly between MS patients and controls, and were unrelated with the age of onset of MS, gender, and course of MS. HLADRB1*1501 showed a high association with the risk of developing MS 4.76(95% C.I.  = 3.14-7.27; p<0.0001. The meta-analysis, after excluding data of one study that was responsible of heterogeneity for rs731236 polymorphism, showed lack of relation of both SNPs with the risk for MS. HLADRB1*1501 showed lack of interaction with VDR rs2228570 and rs731236 in increasing MS risk. CONCLUSIONS: These results suggest that VDR rs2228570 and rs731236 polymorphisms are not related with the risk for MS, and did not confirm interaction between these VDR SNPs and HLADRB1

  9. Study protocol: High-protein nutritional intervention based on β-hydroxy-β-methylbutirate, vitamin D3 and calcium on obese and lean aged patients with hip fractures and sarcopenia. The HIPERPROT-GER study.

    Science.gov (United States)

    Malafarina, Vincenzo; Uriz-Otano, Francisco; Gil-Guerrero, Lucía; Iniesta, Raquel; Zulet, M Angeles; Martinez, J Alfredo

    2013-10-01

    Loss of muscle strength is associated with falls, which, in turn, are the main cause of hip fractures in elderly people. The factors that most influence loss of strength in elderly people are a decrease in muscle mass, i.e. sarcopenia, and an increase in fat, i.e. obesity. A prospective randomized clinical trial among patients who have undergone an operation for a traumatic hip fracture and who are aged 65 or above will be implemented. We shall compare a control diet against a high-protein diet enriched with β-hydroxy-βmethylbutirate, calcium and vitamin D. The diet will be administered during 30 days of hospitalization in the orthopaedic geriatric rehabilitation unit. There will be 50 patients in each arm of the study. The main objective is to assess whether the experimental diet, together with rehabilitation, improves functional recovery, measured on the Barthel index. Secondary objectives are to assess changes in body composition and the prevalence of sarcopenia, obesity and mortality one year after the hip fracture. We shall also assess whether there is a relationship between specific inflammatory markers, sarcopenia and functional recovery. Ageing is accompanied by changes in body composition that increase the risk of falls and progressive functional loss. These factors are a public health problem because they are highly associated with disability in older people. The present study seeks to gain knowledge of those factors that are most often associated with the onset of disability and those that can be modified through diet. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Up-regulation of reciprocal inhibition by explosive strength training

    DEFF Research Database (Denmark)

    Geertsen, Svend Sparre; Jensen, Jesper Lundbye; Nielsen, Jens Bo

    of 26 ± 7 years strength trained the ankle dorsiflexor muscles 3 times a week for 4 weeks. Each training session consisted of 4 sets of 16 isometric dorsiflexions with the aim of increasing force as rapidly as possible, separated by 4min rest periods. Test sessions were conducted before, immediately...... by 6% before the training and by 22% after the training, which was a statistically significant difference (pstrength training in order to ensure efficient suppression of the antagonist...... in the ankle plantarflexors at the onset of dorsiflexion is larger the quicker the movement, we hypothesized that DRI may be up-regulated when subjects are trained to perform dorsiflexion movements as quickly as possible.   For this purpose, 15 healthy human subjects (7 male, 8 female) with an average age...

  11. Rediscovering vitamin D

    African Journals Online (AJOL)

    2010-11-08

    Nov 8, 2010 ... as rickets in children and osteomalacia in adults. In the. 1940s it became mandatory in the United States to fortify milk with vitamin D3, which resulted in a dramatic decline in the incidence of rickets. Consequently, most of the early research focused on the role of vitamin D in regulating calcium balance ...

  12. Vitamin D and allergies

    Directory of Open Access Journals (Sweden)

    Gafvelin Guro

    2013-01-01

    Full Text Available An increasing amount of evidence has established that the biologically active form of vitamin D, 1,25-dihydroxy vitamin D3, possesses immunoregulatory properties. Vitamin D exerts its effects through binding to the nuclear vitamin D receptor (VDR, which is expressed by cells of the immune system. Most of the immunological effects mediated by vitamin D-VDR are regulatory, inhibiting adaptive immune responses. It has become apparent that the incidence of vitamin D insufficiency is surprisingly high in the general population. A link between low vitamin D serum levels and the increased prevalence of allergic diseases has been proposed. This possible connection has been investigated in numerous studies on associations between vitamin D serum concentrations and different allergic conditions, as well as studies on the effect of vitamin D supplementation. Although there is some evidence for a protective role of vitamin D in asthma, no consensus on the role of vitamin D in allergic disease has yet been reached. Still, treatment strategies involving vitamin D supplementation to risk groups, combinatorial corticosteroid and vitamin D treatment in asthma and vitamin D as an immunomodulator in allergen specific immunotherapy show promise for the future.

  13. The Vitamin D for Enhancing the Immune System in Cystic Fibrosis (DISC trial: Rationale and design of a multi-center, double-blind, placebo-controlled trial of high dose bolus administration of vitamin D3 during acute pulmonary exacerbation of cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Vin Tangpricha

    2017-06-01

    Full Text Available Vitamin D deficiency is highly prevalent in children and adults with cystic fibrosis (CF. Recent studies have found an association between vitamin D status and risk of pulmonary exacerbations in children and adults with CF. The ongoing Vitamin D for enhancing the Immune System in Cystic fibrosis (DISC study, a multi-center, double-blind, randomized, placebo-controlled trial, will test the hypothesis of whether high dose vitamin D given as a single oral bolus of 250,000 IU to adults with CF during a pulmonary exacerbation followed by a maintenance dose of vitamin D will improve time to next pulmonary exacerbation and re-hospitalization, improve survival and lung function compared to placebo and reduce the rates of pulmonary exacerbation. Subjects will be randomized 1:1 at each clinical site to vitamin D or placebo within 72 h of hospital admission for pulmonary exacerbation. Clinical follow-up visits will occur at 1, 2, 3, and 7 days, and 1, 3, 6 and 12 months after randomization. Blood and sputum will be collected and determination of clinical outcomes will be assessed at each visit. The primary endpoint will be the time to next pulmonary exacerbation requiring antibiotics, re-hospitalization or death. The secondary endpoints will include lung function assessed by forced expiratory volume in 1 s (FEV1, blood markers of inflammatory cytokines, anti-microbial peptide expression by peripheral blood mononuclear cells and circulating concentrations in blood. Other exploratory endpoints will examine the phenotype of neutrophils and monocyte/macrophages in sputum. Nutritional status will be assessed by 3 day food records and food frequency questionnaire.

  14. Sunlight and Vitamin D

    Science.gov (United States)

    Wacker, Matthias; Holick, Michael F.

    2013-01-01

    Vitamin D is the sunshine vitamin that has been produced on this earth for more than 500 million years. During exposure to sunlight 7-dehydrocholesterol in the skin absorbs UV B radiation and is converted to previtamin D3 which in turn isomerizes into vitamin D3. Previtamin D3 and vitamin D3 also absorb UV B radiation and are converted into a variety of photoproducts some of which have unique biologic properties. Sun induced vitamin D synthesis is greatly influenced by season, time of day, latitude, altitude, air pollution, skin pigmentation, sunscreen use, passing through glass and plastic, and aging. Vitamin D is metabolized sequentially in the liver and kidneys into 25-hydroxyvitamin D which is a major circulating form and 1,25-dihydroxyvitamin D which is the biologically active form respectively. 1,25-dihydroxyvitamin D plays an important role in regulating calcium and phosphate metabolism for maintenance of metabolic functions and for skeletal health. Most cells and organs in the body have a vitamin D receptor and many cells and organs are able to produce 1,25-dihydroxyvitamin D. As a result 1,25-dihydroxyvitamin D influences a large number of biologic pathways which may help explain association studies relating vitamin D deficiency and living at higher latitudes with increased risk for many chronic diseases including autoimmune diseases, some cancers, cardiovascular disease, infectious disease, schizophrenia and type 2 diabetes. A three-part strategy of increasing food fortification programs with vitamin D, sensible sun exposure recommendations and encouraging ingestion of a vitamin D supplement when needed should be implemented to prevent global vitamin D deficiency and its negative health consequences. PMID:24494042

  15. Associations of maternal circulating 25-hydroxyvitamin D3 concentration with pregnancy and birth outcomes.

    Science.gov (United States)

    Rodriguez, A; García-Esteban, R; Basterretxea, M; Lertxundi, A; Rodríguez-Bernal, C; Iñiguez, C; Rodriguez-Dehli, C; Tardón, A; Espada, M; Sunyer, J; Morales, E

    2015-11-01

    To investigate the association of maternal circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration with pregnancy and birth outcomes. Prospective cohort study. Four geographical areas of Spain, 2003-2008. Of 2382 mother-child pairs participating in the INfancia y Medio Ambiente (INMA) Project. Maternal circulating 25(OH)D3 concentration was measured in pregnancy (mean [SD] 13.5 [2.2] weeks of gestation). We tested associations of maternal 25(OH)D3 concentration with pregnancy and birth outcomes. Gestational diabetes mellitus (GDM), preterm delivery, caesarean section, fetal growth restriction (FGR) and small-for-gestational age (SGA), anthropometric birth outcomes including weight, length and head circumference (HC). Overall, 31.8% and 19.7% of women had vitamin D insufficiency [25(OH)D3 20-29.99 ng/ml] and deficiency [25(OH)D3 < 20 ng/ml], respectively. After adjustment, there was no association between maternal 25(OH)D3 concentration and risk of GDM or preterm delivery. Women with sufficient vitamin D [25(OH)D3 ≥ 30 ng/ml] had a decreased risk of caesarean section by obstructed labour compared with women with vitamin D deficiency [relative risk (RR) = 0.60, 95% CI 0.37, 0.97). Offspring of mothers with higher circulating 25(OH)D3 concentration tended to have smaller HC [coefficient (SE) per doubling concentration of 25(OH)D3, -0.10 (0.05), P = 0.038]. No significant associations were found for other birth outcomes. This study did not find any evidence of an association between vitamin D status in pregnancy and GDM, preterm delivery, FGR, SGA and anthropometric birth outcomes. Results suggest that sufficient circulating vitamin D concentration [25(OH)D3 ≥ 30 ng/ml] in pregnancy may reduce the risk of caesarean section by obstructed labour. © 2014 Royal College of Obstetricians and Gynaecologists.

  16. The D3 Middleware Architecture

    Science.gov (United States)

    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. 1,25-dihydroxyvitamin D3 modulates cytokine production induced by Candida albicans: impact of seasonal variation of immune responses

    NARCIS (Netherlands)

    Khoo, A.L.; Chai, L.; Koenen, H.J.P.M.; Kullberg, B.J.; Joosten, I.; Ven, A.J.A.M. van der; Netea, M.G.

    2011-01-01

    BACKGROUND: Our interest in immunological effects produced by vitamin D(3) (1,25(OH)(2)D(3)) and its therapeutic potential prompted us to examine the role of 1,25(OH)(2)D(3) on cytokine production by Candida albicans. METHODS: Peripheral blood mononuclear cells (PBMC) with stimulated C. albicans and

  18. 21 CFR 172.380 - Vitamin D3.

    Science.gov (United States)

    2010-04-01

    ... manufactured by ultraviolet irradiation of 7-dehydrocholesterol produced from cholesterol and is purified by... § 105.66 of this chapter. (5) At levels not to exceed 81 IU per 30 grams in cheese and cheese products as defined under § 170.3(n)(5) of this chapter, excluding cottage cheese, ricotta cheese, and hard...

  19. Effects of 1,25-dihydroxyvitamin D3 on IL-17/IL-23 axis, IFN-γ and IL-4 expression in systemic lupus erythematosus induced mice model

    Directory of Open Access Journals (Sweden)

    Fatemeh Faraji

    2016-04-01

    Conclusion: Our findings showed that vitamin D3 supplementation in lupus induced mice through modulating the expression rate of some inflammatory cytokines diminished the inflammatory conditions in SLE.

  20. Vitamin D vitamers affect vitamin D status differently in young healthy males

    DEFF Research Database (Denmark)

    Jakobsen, Jette; Wreford Andersen, Elisabeth Anne; Christensen, Tue

    2018-01-01

    Dietary intake of vitamin D includes vitamin D3 (vitD3), 25-hydroxyvitamin D3 (25OH-D3), and vitamin D2 (vitD2). However, the bioactivity of the different species has not been scientifically established. The hypothesis in this study was that vitD3, 25OH-D3, and vitD2 have an equal effect on 25......-hydroxyvitamin D in serum (vitamin D status). To test our hypothesis, we performed a randomized, crossover study. Twelve young males consumed 10 µg/day vitD3 during a four-week run-in period, followed by 3 × 6 weeks of 10 µg/day vitD3, 10 µg/day 25OH-D3, and 10 µg/day vitD2. The content of vitD3, vitD2, 25OH-D3......, and 25-hydroxyvitamin D2 (25OH-D2) in serum was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The hypothesis that the three sources of vitamin D affect vitamin D status equally was rejected. Based on the assumption that 1 µg vitD3/day will show an increase in vitamin D status...

  1. Effects of fractionated colostrum replacer and vitamins A, D, and E on haptoglobin and clinical health in neonatal Holstein calves challenged with Mycobacterium avium ssp. paratuberculosis

    Science.gov (United States)

    Thirty Holstein calves were obtained from two dairy farms in central Iowa at birth and randomly assigned to one of six treatment groups: 1) colostrum deprived (CD), no vitamins; 2) colostrum replacer (CR), no vitamins; 3) CR, vitamin A; 4) CR, vitamin D3; 5) CR, vitamin E; 6) CR, vitamins A, D3, E, ...

  2. Vitamin D supplementation for chronic liver diseases in adults

    DEFF Research Database (Denmark)

    Bjelakovic, Goran; Nikolova, Dimitrinka; Bjelakovic, Marko

    2017-01-01

    BACKGROUND: Vitamin D deficiency is often reported in people with chronic liver diseases. Therefore, improving vitamin D status could have a beneficial effect on people with chronic liver diseases. OBJECTIVES: To assess the beneficial and harmful effects of vitamin D supplementation in people...... that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults with chronic liver diseases. Vitamin D could have been administered as supplemental vitamin D (vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol)), or an active form of vitamin D (1α...... in the remaining nine trials were vitamin D insufficient (less than 20 ng/mL). All trials administered vitamin D orally. Mean duration of vitamin D supplementation was 0.5 years and follow-up was 0.6 years. Eleven trials (831 participants; 40% women; mean age 52 years) tested vitamin D3, one trial (18 men; mean...

  3. Hypovitaminosis D3, Leukopenia, and Human Serotonin Transporter Polymorphism in Anorexia Nervosa and Bulimia Nervosa

    Directory of Open Access Journals (Sweden)

    Anna Tasegian

    2016-01-01

    Full Text Available Vitamin D3 has been described to have different extraskeletal roles by acting as parahormone in obesity, diabetes, cancer, cognitive impairment, and dementia and to have important regulatory functions in innate immunity. There are no studies showing extraskeletal changes associated with hypovitaminosis D3 in eating disorders. Methods. We have analyzed the blood of 18 patients affected by anorexia nervosa and bulimia nervosa collected over a 15-month period. We performed a panel of chemical and clinical analyses: the assay of vitamin D3, the immunoblotting of vitamin D receptor and peroxisome proliferator-activated receptor gamma, and the genotyping of 5-hydroxytryptamine transporter linked polymorphic region. Results. We choose 18 patients with a normal blood test profile such as thyroid hormones, hepatic and renal parameters, triglycerides, proteins, vitamin B12, and folic acid. Among these emerged the case of a woman with long-term anorexia nervosa and the case of a woman with long-term bulimia nervosa both complicated by anxiety and depression, severe hypovitaminosis D3, decrease of vitamin D receptor, leukopenia, and 5-hydroxytryptamine transporter linked polymorphic region short allele. Conclusion. The results induce hypothesising that the severe hypovitaminosis D3 might be responsible for the lack of the inflammatory response and the depressive symptoms in patients with long-term eating disorders.

  4. Hypovitaminosis D3, Leukopenia, and Human Serotonin Transporter Polymorphism in Anorexia Nervosa and Bulimia Nervosa.

    Science.gov (United States)

    Tasegian, Anna; Curcio, Francesco; Dalla Ragione, Laura; Rossetti, Francesca; Cataldi, Samuela; Codini, Michela; Ambesi-Impiombato, Francesco Saverio; Beccari, Tommaso; Albi, Elisabetta

    2016-01-01

    Vitamin D3 has been described to have different extraskeletal roles by acting as parahormone in obesity, diabetes, cancer, cognitive impairment, and dementia and to have important regulatory functions in innate immunity. There are no studies showing extraskeletal changes associated with hypovitaminosis D3 in eating disorders. Methods. We have analyzed the blood of 18 patients affected by anorexia nervosa and bulimia nervosa collected over a 15-month period. We performed a panel of chemical and clinical analyses: the assay of vitamin D3, the immunoblotting of vitamin D receptor and peroxisome proliferator-activated receptor gamma, and the genotyping of 5-hydroxytryptamine transporter linked polymorphic region. Results. We choose 18 patients with a normal blood test profile such as thyroid hormones, hepatic and renal parameters, triglycerides, proteins, vitamin B12, and folic acid. Among these emerged the case of a woman with long-term anorexia nervosa and the case of a woman with long-term bulimia nervosa both complicated by anxiety and depression, severe hypovitaminosis D3, decrease of vitamin D receptor, leukopenia, and 5-hydroxytryptamine transporter linked polymorphic region short allele. Conclusion. The results induce hypothesising that the severe hypovitaminosis D3 might be responsible for the lack of the inflammatory response and the depressive symptoms in patients with long-term eating disorders.

  5. Induction of regulatory dendritic cells by dexamethasone and 1alpha,25-Dihydroxyvitamin D(3)

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Gad, Monika; Walter, Mark R

    2004-01-01

    Dendritic cells (DC) modulated to induce T cell hyporesponsiveness have promising potential in immunotherapy of autoimmune disorders and for the prevention of allograft rejection. While studying the effect of immunosuppressive agents on the maturation of DC we found that 1alpha,25-Dihydroxyvitami...... D(3) the active form of Vitamin D(3) (D(3)) in combination with dexamethasone (Dex) has a synergistic effect on LPS-induced maturation of DC. Monocyte-derived DCs cultured with D(3) and Dex during LPS-induced maturation have a low stimulatory effect on allogeneic T cells comparable...

  6. Vitamins as hormones.

    Science.gov (United States)

    Reichrath, J; Lehmann, B; Carlberg, C; Varani, J; Zouboulis, C C

    2007-02-01

    system is documented by the fact that the skin is both the site of vitamin D (3)- and 1,25-dihydroxyvitamin D (3) [1, 25(OH) (2)D (3)]-synthesis and a target organ for 1,25(OH) (2)D (3). 1,25(OH) (2)D (3) is not only essential for mineral homeostasis and bone integrity, but also for numerous further physiologic functions including regulation of growth and differentiation in a broad variety of normal and malignant tissues, including cells derived from prostate, breast and bone. In keratinocytes and other cell types, 1,25(OH) (2)D (3) regulates growth and differentiation. Consequently, vitamin D analogues have been introduced for the treatment of the hyperproliferative skin disease psoriasis. Other newly detected functions of vitamin D analogues include profound effects on the immune system as well as protection against cancer and other diseases, including autoimmune and infectious diseases, in various tissues. Current investigation of the biological effects of vitamin D analogues are likely to lead to new therapeutic applications that, besides cancer prevention, may include the prevention and treatment of infectious as well as of inflammatory skin diseases. This review summarizes existing knowledge on vitamins A and D, the major vitamin-hormones of the skin.

  7. Placental vitamin D metabolism and its associations with circulating vitamin D metabolites in pregnant women.

    Science.gov (United States)

    Park, Heyjun; Wood, Madeleine R; Malysheva, Olga V; Jones, Sara; Mehta, Saurabh; Brannon, Patsy M; Caudill, Marie A

    2017-12-01

    Background: Little is known about placental vitamin D metabolism and its impact on maternal circulating vitamin D concentrations in humans. Objective: This study sought to advance the current understanding of placental vitamin D metabolism and its role in modulating maternal circulating vitamin D metabolites during pregnancy. Design: Nested within a feeding study, 24 healthy pregnant women (26-29 wk of gestation) consumed a single amount of vitamin D (511 IU/d from diet and a cholecalciferol supplement) for 10 wk. Concentrations of placental and blood vitamin D metabolites and placental messenger RNA (mRNA) abundance of vitamin D metabolic pathway components were quantified. In addition, cultured human trophoblasts were incubated with 13 C-cholecalciferol to examine the intracellular generation and secretion of vitamin D metabolites along with the regulation of target genes. Results: In placental tissue, 25-hydroxyvitamin D 3 [25(OH)D 3 ] was strongly correlated ( r = 0.83, P vitamin D metabolic components and circulating vitamin D metabolites [i.e., LDL-related protein 2 ( LRP2 , also known as megalin) with 25(OH)D 3 and the C3 epimer of 25(OH)D 3 [3-epi-25(OH)D 3 ]; cubilin ( CUBN ) with 25(OH)D 3 ; 25-hydroxylase ( CYP2R1 ) with 3-epi-25(OH)D 3 ; 24-hydroxylase ( CYP24A1 ) with 25(OH)D 3 , 3-epi-25(OH)D 3 , and 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]; and 1α-hydroxylase [( CYP27B1 ) with 3-epi-25(OH)D 3 and 1,25(OH) 2 D 3 ]. Notably, in vitro experiments with trophoblasts showed increased production and secretion of 25(OH)D 3 and higher CYP24A1 gene transcript abundance in response to cholecalciferol treatment. Conclusions: The numerous associations of many of the placental biomarkers of vitamin D metabolism with circulating vitamin D metabolites among pregnant women [including a CYP27B1 -associated increase in 1,25(OH) 2 D 3 ] and the evidence of trophoblast production and secretion of vitamin D metabolites, especially 25(OH)D 3 , suggest that the placenta

  8. 25 (OH) D3 levels, incidence and recurrence of different clinical forms of BPPV.

    Science.gov (United States)

    Maslovara, Sinisa; Butkovic Soldo, Silva; Sestak, Anamarija; Milinkovic, Katarina; Rogic-Namacinski, Jasna; Soldo, Anamarija

    2017-06-11

    Benign Paroxysmal Positional Vertigo (BPPV) is the most common cause of dizziness in the general population. It is a condition with potential impact of reduced levels of vitamin D on its recurrent attacks. The aim of this study was to measure the serum levels of 25-hydroxyvitamin D3 (25-OH D3) in patients with BPPV and determine whether there is a difference in the serum levels of vitamin D3 between patients with and without recurrence, as well as between the different clinical forms of BPPV. The study included 40 patients who came to the regular medical examination, diagnosed with PC-BPPV based on the positive Dix-Hallpike's test. All patients underwent Epley manoeuvre after the diagnosis. Patients were classified according to current guidelines for levels of vitamin D3 in the serum in three groups: the deficiency, insufficiency and adequate level. The average serum level of 25-OH D3 among respondents was 20.78ng/mL, indicating a lack or insufficiency of the aforementioned 25-OH D3. According to the levels of 25-OH D3, most patients suffer from deficiency (47.5%). 7 (17.5%) respondents had adequate blood level of 25-OH D3, and 14 (35%) respondents suffer from insufficiency. A significant difference was not found in the serum level of 25-OH D3 between patients with and without BPPV recurrence. There was a significant difference in the serum levels of 25-OH D3 in comparison to the clinical form of the disease. Lower 25-OH D3 values were found in patients with canalithiasis compared to those with cupulolithiasis. There were no significant differences in the vitamin D3 serum level in patients with and without recurrence. The study showed a low level of serum vitamin D3 in most patients, indicating the need for supplemental therapy. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  9. 7 CFR 15d.3 - Compliance.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Compliance. 15d.3 Section 15d.3 Agriculture Office of the Secretary of Agriculture NONDISCRIMINATION IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.3 Compliance. The Director of the Office of Civil Rights shall...

  10. Vitamin D Supplementation in Submariners

    Science.gov (United States)

    2008-12-02

    solar exposure since the melanin absorbs some of the UV energy required to manufacture vit D3.65 At higher latitudes, such as New York, winter...Philadelphia, Penn: Lippincott Williams and Wilkins; 1999:315-319. 24. Carlberg C, Polly P. Gene regulation by vitamin D3. Crit Rev Eukaryot Gene

  11. Overestimation of 25-hydroxyvitamin D3 by increased ionisation efficiency of 3-epi-25-hydroxyvitamin D3 in LC-MS/MS methods not separating both metabolites as determined by an LC-MS/MS method for separate quantification of 25-hydroxyvitamin D3, 3-epi-25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in human serum.

    Science.gov (United States)

    van den Ouweland, Johannes M W; Beijers, Antonius M; van Daal, Henny

    2014-09-15

    An LC-MS/MS method was developed for simultaneous quantification of 25-hydroxyvitamin D3 (25(OH)D3), 3-epi-25(OH)D3, and 25(OH)D2 in human serum. Sample preparation consisted of protein precipitation followed by off-line SPE. Calibration curves for each vitamin D metabolite were constructed in phosphate-buffered saline with 60 g/L albumin including its corresponding stable isotope labelled (SIL) internal standard. A pentafluorophenyl (PFP) analytical column was used to resolve 25(OH)D3 from 25(OH)D2 and 3-epi-25(OH)D3, followed by SRM registration using positive ESI-MS/MS. Accuracy was assessed from measurement of samples with NIST reference method procedure (RMP) assigned values. The PFP LC-MS/MS method was compared to an in-house C18 column LC-MS/MS method, not resolving 25(OH)D3 from 3-epi-25(OH)D3, using adult and newborn samples. Intra-assay and inter-assay coefficients of variation were less than 4% and 7.5%, respectively for all three vitamin D metabolites; lower limits of quantification were 1, 1 and 2 nmol/L and linearity of methods were 1-500, 1-200 and 2-500 nmol/L for 25(OH)D3, 3-epi-25(OH)D3 and 25(OH)D2, respectively. The PFP LC-MS/MS method showed minimal bias to the NIST RMP. Method comparison revealed that in the C18 LC-MS/MS method, the 3-epi-25(OH)D3 concentration is overestimated inadvertently not only from co-elution of both analytes, but also by an additional 30-40% higher ionisation efficiency of 3-epi-25(OH)D3 when compared to 25(OH)D3. This accurate LC-MS/MS method allows the simultaneous measurement of 25(OH)D3, 3-epi-25(OH)D3, and 25(OH)D2 in human serum. Due to increased ionisation efficiency, the contribution of the 3-epi-25(OH)D3 metabolite to the total 25(OH)D3 concentration is significantly overestimated in MS methods that do not resolve 3-epi-25(OH)D3 from 25(OH)D3 and may compromise its use in infant samples known to have significant amounts of 3-epi-25(OH)D3. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Effects of 1,25-dihydroxyvitamin D3 on pathological changes in rats with diabetic cardiomyopathy

    OpenAIRE

    Zeng, Xiaoyun; Yu, Xintian; Xiao, Shan; Yao, Hua; Zhu, Jun

    2017-01-01

    Background The role of 1,25-dihydroxyvitamin D3 (vitamin D) in the apoptosis of diabetic cardiomyopathy (DCM) is unclear. This study is to investigate the effects of vitamin D on the pathological changes in rats with DCM. Methods Rats were randomly divided into the control, model, and treatment groups. DCM model was established by the high-fat and -sugar diet. Plasma glucose, body weight, heart weight, heart weight index, and serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK...

  13. Characterization of the autocrine/paracrine function of vitamin D in human gingival fibroblasts and periodontal ligament cells.

    Directory of Open Access Journals (Sweden)

    Kaining Liu

    Full Text Available BACKGROUND: We previously demonstrated that 25-hydroxyvitamin D(3, the precursor of 1α,25-dihydroxyvitamin D(3, is abundant around periodontal soft tissues. Here we investigate whether 25-hydroxyvitamin D(3 is converted to 1α,25-dihydroxyvitamin D(3 in periodontal soft tissue cells and explore the possibility of an autocrine/paracrine function of 1α,25-dihydroxyvitamin D(3 in periodontal soft tissue cells. METHODOLOGY/PRINCIPAL FINDINGS: We established primary cultures of human gingival fibroblasts and human periodontal ligament cells from 5 individual donors. We demonstrated that 1α-hydroxylase was expressed in human gingival fibroblasts and periodontal ligament cells, as was cubilin. After incubation with the 1α-hydroxylase substrate 25-hydroxyvitamin D(3, human gingival fibroblasts and periodontal ligament cells generated detectable 1α,25-dihydroxyvitamin D(3 that resulted in an up-regulation of CYP24A1 and RANKL mRNA. A specific knockdown of 1α-hydroxylase in human gingival fibroblasts and periodontal ligament cells using siRNA resulted in a significant reduction in both 1α,25-dihydroxyvitamin D(3 production and mRNA expression of CYP24A1 and RANKL. The classical renal regulators of 1α-hydroxylase (parathyroid hormone, calcium and 1α,25-dihydroxyvitamin D(3 and Porphyromonas gingivalis lipopolysaccharide did not influence 1α-hydroxylase expression significantly, however, interleukin-1β and sodium butyrate strongly induced 1α-hydroxylase expression in human gingival fibroblasts and periodontal ligament cells. CONCLUSIONS/SIGNIFICANCE: In this study, the expression, activity and functionality of 1α-hydroxylase were detected in human gingival fibroblasts and periodontal ligament cells, raising the possibility that vitamin D acts in an autocrine/paracrine manner in these cells.

  14. Vitamin D4 in mushrooms.

    Science.gov (United States)

    Phillips, Katherine M; Horst, Ronald L; Koszewski, Nicholas J; Simon, Ryan R

    2012-01-01

    An unknown vitamin D compound was observed in the HPLC-UV chromatogram of edible mushrooms in the course of analyzing vitamin D(2) as part of a food composition study and confirmed by liquid chromatography-mass spectrometry to be vitamin D(4) (22-dihydroergocalciferol). Vitamin D(4) was quantified by HPLC with UV detection, with vitamin [(3)H] itamin D(3) as an internal standard. White button, crimini, portabella, enoki, shiitake, maitake, oyster, morel, chanterelle, and UV-treated portabella mushrooms were analyzed, as four composites each of a total of 71 samples from U.S. retail suppliers and producers. Vitamin D(4) was present (>0.1 µg/100 g) in a total of 18 composites and in at least one composite of each mushroom type except white button. The level was highest in samples with known UV exposure: vitamin D enhanced portabella, and maitake mushrooms from one supplier (0.2-7.0 and 22.5-35.4 µg/100 g, respectively). Other mushrooms had detectable vitamin D(4) in some but not all samples. In one composite of oyster mushrooms the vitamin D(4) content was more than twice that of D(2) (6.29 vs. 2.59 µg/100 g). Vitamin D(4) exceeded 2 µg/100 g in the morel and chanterelle mushroom samples that contained D(4), but was undetectable in two morel samples. The vitamin D(4) precursor 22,23-dihydroergosterol was found in all composites (4.49-16.5 mg/100 g). Vitamin D(4) should be expected to occur in mushrooms exposed to UV light, such as commercially produced vitamin D enhanced products, wild grown mushrooms or other mushrooms receiving incidental exposure. Because vitamin D(4) coeluted with D(3) in the routine HPLC analysis of vitamin D(2) and an alternate mobile phase was necessary for resolution, researchers analyzing vitamin D(2) in mushrooms and using D(3) as an internal standard should verify that the system will resolve vitamins D(3) and D(4).

  15. Vitamin D4 in mushrooms.

    Directory of Open Access Journals (Sweden)

    Katherine M Phillips

    Full Text Available An unknown vitamin D compound was observed in the HPLC-UV chromatogram of edible mushrooms in the course of analyzing vitamin D(2 as part of a food composition study and confirmed by liquid chromatography-mass spectrometry to be vitamin D(4 (22-dihydroergocalciferol. Vitamin D(4 was quantified by HPLC with UV detection, with vitamin [(3H] itamin D(3 as an internal standard. White button, crimini, portabella, enoki, shiitake, maitake, oyster, morel, chanterelle, and UV-treated portabella mushrooms were analyzed, as four composites each of a total of 71 samples from U.S. retail suppliers and producers. Vitamin D(4 was present (>0.1 µg/100 g in a total of 18 composites and in at least one composite of each mushroom type except white button. The level was highest in samples with known UV exposure: vitamin D enhanced portabella, and maitake mushrooms from one supplier (0.2-7.0 and 22.5-35.4 µg/100 g, respectively. Other mushrooms had detectable vitamin D(4 in some but not all samples. In one composite of oyster mushrooms the vitamin D(4 content was more than twice that of D(2 (6.29 vs. 2.59 µg/100 g. Vitamin D(4 exceeded 2 µg/100 g in the morel and chanterelle mushroom samples that contained D(4, but was undetectable in two morel samples. The vitamin D(4 precursor 22,23-dihydroergosterol was found in all composites (4.49-16.5 mg/100 g. Vitamin D(4 should be expected to occur in mushrooms exposed to UV light, such as commercially produced vitamin D enhanced products, wild grown mushrooms or other mushrooms receiving incidental exposure. Because vitamin D(4 coeluted with D(3 in the routine HPLC analysis of vitamin D(2 and an alternate mobile phase was necessary for resolution, researchers analyzing vitamin D(2 in mushrooms and using D(3 as an internal standard should verify that the system will resolve vitamins D(3 and D(4.

  16. 25-hydroxyvitamin D circulates in different fractions of calf plasma if the parent compound is vitamin D2 or vitamin D3 respectively

    DEFF Research Database (Denmark)

    Hymøller, Lone; Jensen, Søren Krogh

    2016-01-01

    dairy cows with sufficient vitamin D. However, choosing the most efficient route and form of supplementation requires insight into how different vitamin D metabolites are transported in the body of cattle. There are two forms of vitamin D: vitamin D2 (D2) and vitamin D3 (D3). Vitamin D2 originates from......Vitamin D has become one of the most discussed nutrients in human nutrition, which has led to an increased interest in milk as a vitamin D source. Problems related to fortifying milk with synthetic vitamin D can be avoided by securing a high content of natural vitamin D in the milk by supplying...

  17. Vitamin D metabolism and effects on pluripotency genes and cell differentiation in testicular germ cell tumors in vitro and in vivo

    DEFF Research Database (Denmark)

    Blomberg Jensen, Martin; Jørgensen, Anne; Nielsen, John Erik

    2012-01-01

    and express pluripotency factors (NANOG/OCT4). Vitamin D (VD) is metabolized in the testes, and here, we examined VD metabolism in TGCT differentiation and pluripotency regulation. We established that the VD receptor (VDR) and VD-metabolizing enzymes are expressed in human fetal germ cells, CIS, and invasive......) downregulated NANOG and OCT4 through genomic VDR activation in EC-derived NTera2 cells and, to a lesser extent, in seminoma-derived TCam-2 cells, and up-regulated brachyury, SNAI1, osteocalcin, osteopontin, and fibroblast growth factor 23. To test for a possible therapeutic effect in vivo, NTera2 cells were...... xenografted into nude mice and treated with 1,25(OH)(2)D(3), which induced down-regulation of pluripotency factors but caused no significant reduction of tumor growth. During NTera2 tumor formation, down-regulation of VDR was observed, resulting in limited responsiveness to cholecalciferol and 1,25(OH)(2)D(3...

  18. 25-Hydroxyvitamin D3-deficiency enhances oxidative stress and corticosteroid resistance in severe asthma exacerbation.

    Directory of Open Access Journals (Sweden)

    Nan Lan

    Full Text Available 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.

  19. Mechanisms of Hypoxic Up-Regulation of Versican Gene Expression in Macrophages.

    Directory of Open Access Journals (Sweden)

    Fattah Sotoodehnejadnematalahi

    Full Text Available Hypoxia is a hallmark of many pathological tissues. Macrophages accumulate in hypoxic sites and up-regulate a range of hypoxia-inducible genes. The matrix proteoglycan versican has been identified as one such gene, but the mechanisms responsible for hypoxic induction are not fully characterised. Here we investigate the up-regulation of versican by hypoxia in primary human monocyte-derived macrophages (HMDM, and, intriguingly, show that versican mRNA is up-regulated much more highly (>600 fold by long term hypoxia (5 days than by 1 day of hypoxia (48 fold. We report that versican mRNA decay rates are not affected by hypoxia, demonstrating that hypoxic induction of versican mRNA is mediated by increased transcription. Deletion analysis of the promoter identified two regions required for high level promoter activity of luciferase reporter constructs in human macrophages. The hypoxia-inducible transcription factor HIF-1 has previously been implicated as a key potential regulator of versican expression in hypoxia, however our data suggest that HIF-1 up-regulation is unlikely to be principally responsible for the high levels of induction observed in HMDM. Treatment of HMDM with two distinct specific inhibitors of Phosphoinositide 3-kinase (PI3K, LY290042 and wortmannin, significantly reduced induction of versican mRNA by hypoxia and provides evidence of a role for PI3K in hypoxic up-regulation of versican expression.

  20. Dopamine D3 receptor ligands for drug addiction treatment: update on recent findings.

    Science.gov (United States)

    Le Foll, Bernard; Collo, Ginetta; Rabiner, Eugenii A; Boileau, Isabelle; Merlo Pich, Emilio; Sokoloff, Pierre

    2014-01-01

    The dopamine D3 receptor is located in the limbic area and apparently mediates selective effects on motivation to take drugs and drug-seeking behaviors, so that there has been considerable interest on the possible use of D3 receptor ligands to treat drug addiction. However, only recently selective tools allowing studying this receptor have been developed. This chapter presents an overview of findings that were presented at a symposium on the conference Dopamine 2013 in Sardinia in May 2013. Novel neurobiological findings indicate that drugs of abuse can lead to significant structural plasticity in rodent brain and that this is dependent on the availability of functional dopamine D3 autoreceptor, whose activation increased phosphorylation in the ERK pathway and in the Akt/mTORC1 pathway indicating the parallel engagement of a series of intracellular signaling pathways all involved in cell growth and survival. Preclinical findings using animal models of drug-seeking behaviors confirm that D3 antagonists have a promising profile to treat drug addiction across drugs of abuse type. Imaging the D3 is now feasible in human subjects. Notably, the development of (+)-4-propyl-9-hydroxynaphthoxazine ligand used in positron emission tomography (PET) studies in humans allows to measure D3 and D2 receptors based on the area of the brain under study. This PET ligand has been used to confirm up-regulation of D3 sites in psychostimulant users and to reveal that tobacco smoking produces elevation of dopamine at the level of D3 sites. There are now novel antagonists being developed, but also old drugs such as buspirone, that are available to test the D3 hypothesis in humans. The first results of clinical investigations are now being provided. Overall, those recent findings support further exploration of D3 ligands to treat drug addiction. © 2014 Elsevier B.V. All rights reserved.

  1. A holographic bound for D3-brane

    Energy Technology Data Exchange (ETDEWEB)

    Momeni, Davood; Myrzakul, Aizhan; Myrzakulov, Ratbay [Eurasian National University, Eurasian International Center for Theoretical Physics, Astana (Kazakhstan); Eurasian National University, Department of General Theoretical Physics, Astana (Kazakhstan); Faizal, Mir [University of British Columbia-Okanagan, Irving K. Barber School of Arts and Sciences, Kelowna, BC (Canada); University of Lethbridge, Department of Physics and Astronomy, Lethbridge, AB (Canada); Bahamonde, Sebastian [University College London, Department of Mathematics, London (United Kingdom)

    2017-06-15

    In this paper, we will regularize the holographic entanglement entropy, holographic complexity and fidelity susceptibility for a configuration of D3-branes. We will also study the regularization of the holographic complexity from the action for a configuration of D3-branes. It will be demonstrated that for a spherical shell of D3-branes the regularized holographic complexity is always greater than or equal to the regularized fidelity susceptibility. Furthermore, we will also demonstrate that the regularized holographic complexity is related to the regularized holographic entanglement entropy for this system. Thus, we will obtain a holographic bound involving regularized holographic complexity, regularized holographic entanglement entropy and regularized fidelity susceptibility of a configuration of D3-brane. We will also discuss a bound for regularized holographic complexity from action, for a D3-brane configuration. (orig.)

  2. DMPD: Mechanism of age-associated up-regulation in macrophage PGE2 synthesis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15331118 Mechanism of age-associated up-regulation in macrophage PGE2 synthesis. Wu...e-associated up-regulation in macrophage PGE2 synthesis. PubmedID 15331118 Title Mechanism of age-associated... up-regulation in macrophage PGE2 synthesis. Authors Wu D, Meydani SN. Publicatio

  3. Natural vitamin D content in animal products.

    Science.gov (United States)

    Schmid, Alexandra; Walther, Barbara

    2013-07-01

    Humans derive most vitamin D from the action of sunlight in their skin. However, in view of the current Western lifestyle with most daily activities taking place indoors, sun exposure is often not sufficient for adequate vitamin D production. For this reason, dietary intake is also of great importance. Animal foodstuffs (e.g., fish, meat, offal, egg, dairy) are the main sources for naturally occurring cholecalciferol (vitamin D-3). This paper therefore aims to provide an up-to-date overview of vitamin D-3 content in various animal foods. The focus lies on the natural vitamin D-3 content because there are many countries in which foods are not regularly fortified with vitamin D. The published data show that the highest values of vitamin D are found in fish and especially in fish liver, but offal also provides considerable amounts of vitamin D. The content in muscle meat is generally much lower. Vitamin D concentrations in egg yolks range between the values for meat and offal. If milk and dairy products are not fortified, they are normally low in vitamin D, with the exception of butter because of its high fat content. However, as recommendations for vitamin D intake have recently been increased considerably, it is difficult to cover the requirements solely by foodstuffs.

  4. Vitamin D and Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Muyesser Saykı Arslan

    2014-10-01

    Full Text Available Accumulating evidence demonstrated that the active form of vitamin D, 1,25(OH2D3, has an antiproliferative, anti-apopitotic and prodifferentiating effects in several tumour types in preclinical studies. Several studies reported the impact of vitamin D on cancer risk particularly in breast and colorectal cancer however, its effect on thyroid cancer is less known. This review focuses on the relationship of vitamin D and thyroid cancer under the light of the litherature. Thyroid cancer is the most common endocrine cancer and also vitamin D deficiency is a common condition throughout the world. Some clinical studies showed that vitamin D deficiency is higher in patients with thyroid cancer. Preclinical studies evidenced that vitamin D has an effect on differentiation, reduction in tumor burden, and prevention of metastatic growth in thyroid cancer used alone or in combination with anticancer drugs. However, further clinical studies are needed to understand its impact on prognosis of thyroid cancer.

  5. Vitamin A supplementation and risk of atopy

    DEFF Research Database (Denmark)

    Kiraly, Nicholas; Balde, Aliu; Lisse, Ida Marie

    2013-01-01

    The World Health Organization recommends high-dose vitamin A supplementation (VAS) for children above six months of age in low-income countries. VAS has been associated with up-regulation of the Th2 response. We aimed to determine if VAS is associated with atopy in childhood....

  6. Dimensional reduction for D3-brane moduli

    Energy Technology Data Exchange (ETDEWEB)

    Cownden, Brad [Department of Physics & Astronomy, University of Manitoba,Winnipeg, Manitoba R3T 2N2 (Canada); Frey, Andrew R. [Department of Physics & Astronomy, University of Manitoba,Winnipeg, Manitoba R3T 2N2 (Canada); Department of Physics, University of Winnipeg,Winnipeg, Manitoba R3B 2E9 (Canada); Marsh, M.C. David [Department of Applied Mathematics and Theoretical Physics, University of Cambridge,Cambridge, CB3 0WA (United Kingdom); Underwood, Bret [Department of Physics, Pacific Lutheran University,Tacoma, WA 98447 (United States)

    2016-12-28

    Warped string compactifications are central to many attempts to stabilize moduli and connect string theory with cosmology and particle phenomenology. We present a first-principles derivation of the low-energy 4D effective theory from dimensional reduction of a D3-brane in a warped Calabi-Yau compactification of type IIB string theory with imaginary self-dual 3-form flux, including effects of D3-brane motion beyond the probe approximation, and find the metric on the moduli space of brane positions, the universal volume modulus, and axions descending from the 4-form potential. As D3-branes may be considered as carrying either electric or magnetic charges for the self-dual 5-form field strength, we present calculations in both duality frames. Our results are consistent with, but extend significantly, earlier results on the low-energy effective theory arising from D3-branes in string compactifications.

  7. Suppression of murine experimental autoimmune encephalomyelitis development by 1,25-dihydroxyvitamin D3 with autophagy modulation.

    Science.gov (United States)

    Zhen, Chao; Feng, Xuedan; Li, Zhe; Wang, Yabo; Li, Bin; Li, Lin; Quan, Moyuan; Wang, Gaoning; Guo, Li

    2015-03-15

    Multiple sclerosis (MS) has been associated with a history of sub-optimal exposure to ultraviolet light, implicating vitamin D3 as a possible protective agent. We evaluated whether 1,25(OH)2D3 attenuates the progression of experimental autoimmune encephalomyelitis (EAE), and explored its potential mechanisms. EAE was induced in C57BL/6 mice via immunization with MOG35-55, and some mice received 1,25(OH)2D3. 1,25(OH)2D3 inhibited EAE progression. Additionally, 1,25(OH)2D3 reduced inflammation, demyelination, and neuron loss in the spinal cord. The protective effect of 1,25(OH)2D3 was associated with significantly elevated expression of Beclin1, increased Bcl-2/Bax ratio, and decreased LC3-II accumulation. Thus, 1,25(OH)2D3 may represent a promising new MS treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. 1,25-Dihydroxyvitamin D3 inhibits the differentiation and migration of T(H17 cells to protect against experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Jae-Hoon Chang

    Full Text Available BACKGROUND: Vitamin D(3, the most physiologically relevant form of vitamin D, is an essential organic compound that has been shown to have a crucial effect on the immune responses. Vitamin D(3 ameliorates the onset of the experimental autoimmune encephalomyelitis (EAE; however, the direct effect of vitamin D(3 on T cells is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In an in vitro system using cells from mice, the active form of vitamin D(3 (1,25-dihydroxyvitamin D(3 suppresses both interleukin (IL-17-producing T cells (T(H17 and regulatory T cells (Treg differentiation via a vitamin D receptor signal. The ability of 1,25-dihydroxyvitamin D(3 (1,25(OH(2D(3 to reduce the amount of IL-2 regulates the generation of Treg cells, but not T(H17 cells. Under T(H17-polarizing conditions, 1,25(OH(2D(3 helps to increase the numbers of IL-10-producing T cells, but 1,25(OH(2D(3's negative regulation of T(H17 development is still defined in the IL-10(-/- T cells. Although the STAT1 signal reciprocally affects the secretion of IL-10 and IL-17, 1,25(OH(2D(3 inhibits IL-17 production in STAT1(-/- T cells. Most interestingly, 1,25(OH(2D(3 negatively regulates CCR6 expression which might be essential for T(H17 cells to enter the central nervous system and initiate EAE. CONCLUSIONS/SIGNIFICANCE: Our present results in an experimental murine model suggest that 1,25(OH(2D(3 can directly regulate T cell differentiation and could be applied in preventive and therapeutic strategies for T(H17-mediated autoimmune diseases.

  9. Data visualization with D3.js cookbook

    CERN Document Server

    Zhu, Nick Qi

    2013-01-01

    Packed with practical recipes, this is a step-by-step guide to learning data visualization with D3 with the help of detailed illustrations and code samples.If you are a developer familiar with HTML, CSS, and JavaScript, and you wish to get the most out of D3, then this book is for you. This book can also serve as a desktop quick-reference guide for experienced data visualization developers.

  10. MDP Up-Regulates the Gene Expression of Type I Interferons in Human Aortic Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Xiumei Xie

    2012-03-01

    Full Text Available Muramyldipeptide (MDP, the minimum essential structure responsible for the immuno-adjuvant activity of peptidoglycan, is recognized by intracellular nuclear-binding oligomerization domain 2 (NOD2. Here, we obtained evidence that the treatment of human aortic endothelial cells (HAECs with MDP up-regulated the gene expression of type I interferons in a dose- and time-dependent manner. MDP also up-regulated the expression of the receptor NOD2, suggesting that MDP may induce a positive feedback response. The up-regulation of interferons was not dependent on the TNFa signaling, as HAECs did not express TNFa with the stimulation of MDP, and TNFa neutralizing antibody did not decrease the induction of IFNs induced by MDP. RT-PCR results showed that HAECs expressed the gene transcripts of interferon regulatory factor (IRF 1, 2, 3, 9. The western blot results showed that MDP induced the phosphorylation of IRF3. These results suggested that MDP induced the up-regulation of gene transcript of interferons through the activation of IRF3 signaling pathway. Meanwhile, MDP induced the gene expression of pro-inflammatory cytokines, including IL-1ß, IL-8, and MCP-1. Taken together, these results suggested that HAECs may play roles in the anti-infection immune response and in the induction of innate immunity.

  11. Cotton Benzoquinone Reductase: Up-regulation During Early Cotton Fiber Developement

    Science.gov (United States)

    Benzoquinone reductase (BR; EC 1.6.5.7) is an enzyme that catalyzes the bivalent redox reactions of quinones without the production of free radical intermediates. Using 2-D PAGE comparisons, two proteins were found to be up-regulated in wild-type cotton ovules during the fiber initiation stage but ...

  12. Plasma concentrations of 25-hydroxyvitamin D among Jordanians: Effect of biological and habitual factors on vitamin D status

    OpenAIRE

    Mallah, Eyad M; Hamad, Mohammad F; ElManaseer, Mays A; Qinna, Nidal A; Idkaidek, Nasir M; Arafat, Tawfiq A; Matalka, Khalid Z

    2011-01-01

    Abstract Background Vitamin D is cutaneously synthesized following sun exposure (vitamin D3) as well as it is derived from dietary intake (vitamin D3 and D2). Vitamin D2 and D3 are metabolized in the liver to 25-hydroxyvitamin D (25(OH)D). This metabolite is considered the functional indicator of vitamin D stores in humans. Since Jordan latitude is 31°N, cutaneous synthesis of vitamin D3 should be sufficient all year round. However, many indications reveal that it is not the case. Thus, this ...

  13. Effect of 1,24R-dihydroxyvitamin D3 on the growth of human keratinocytes.

    LENUS (Irish Health Repository)

    Matsumoto, K

    1990-02-01

    The effect of 1,24R-dihydroxyvitamin D3 (1,24R(OH)2D3), a synthetic analogue of a biologically active form of vitamin D3 (1,25-dihydroxyvitamin D3, 1,25(OH)2D3), on the growth of human keratinocytes cultured in serum-free medium was investigated. The growth of cultured normal human keratinocytes was inhibited by 65% by 10(-8)M 1,24R(OH)2D3 and by 90% by 10(-7)M 1,24(OH)2D3. It inhibited cell growth almost completely at 10(-6)M. The DNA synthesis of keratinocytes was also inhibited with 1,24R(OH)2D3 by 27% at 10(-8)M, 59% at 10(-7)M, and 92% at 10(-6)M. The inhibition of cell growth and DNA synthesis were more remarkable by 1,24R(OH)2D3 than by 1,25(OH)2D3. 1,24R(OH)2D3 also inhibited the growth of keratinocytes derived from patients with psoriasis vulgaris; the growth inhibitory effect was again more remarkable with 1,24R(OH)2D3 than with 1,25(OH)2D3. The viability and protein synthesis of keratinocytes were not affected by 1,24R(OH)2D3, suggesting that the growth inhibitory effect is due to its biological activity, not to cytotoxicity. The binding of [3H]-labeled 1,25(OH)2D3 to its receptor in the cytosolic fraction of cultured keratinocytes was competitively substituted by unlabeled 1,24R(OH)2D3 as well as 1,25(OH)2D3, suggesting that 1,24R(OH)2D3 binds to the 1,25(OH)2D3 receptor. It was found that the affinity of 1,24R(OH)2D3 for the receptor was slightly higher than that of 1,25(OH)2D3. These results demonstrate that 1,24R(OH)2D3 functions as a potent growth inhibitor in vitro in human keratinocytes from both normal and psoriatic epidermis, and it possesses a higher affinity for the 1,25(OH)2D3 receptor in cultured human keratinocytes. The difference in affinity of 1,24R(OH)2D3 for the 1,25(OH)2D3 receptor correlates with its greater inhibition of keratinocyte growth than 1,25(OH)2D3. 1,24R(OH)2D3 may be useful in the treatment of psoriasis.

  14. The emerging role of m-TOR up-regulation in brain Astrocytoma.

    Science.gov (United States)

    Ryskalin, Larisa; Limanaqi, Fiona; Biagioni, Francesca; Frati, Alessandro; Esposito, Vincenzo; Calierno, Maria Teresa; Lenzi, Paola; Fornai, Francesco

    2017-05-01

    The present manuscript is an overview of various effects of mTOR up-regulation in astrocytoma with an emphasis on its deleterious effects on the proliferation of Glioblastoma Multiforme. The manuscript reports consistent evidence indicating the occurrence of mTOR up-regulation both in experimental and human astrocytoma. The grading of human astrocytoma is discussed in relationship with mTOR up-regulation. In the second part of the manuscript, the biochemical pathways under the influence of mTOR are translated to cell phenotypes which are generated by mTOR up-regulation and reverted by its inhibition. A special section is dedicated to the prominent role of autophagy in mediating the effects of mTOR in glioblastoma. In detail, autophagy inhibition produced by mTOR up-regulation determines the fate of cancer stem cells. On the other hand, biochemical findings disclose the remarkable effects of autophagy activators as powerful inducers of cell differentiation with a strong prevalence towards neuronal phenotypes. Thus, mTOR modulation acts on the neurobiology of glioblastoma just like it operates in vivo at the level of brain stem cell niches by altering autophagy-dependent cell differentiation. In the light of such a critical role of autophagy we analyzed the ubiquitin proteasome system. The merging between autophagy and proteasome generates a novel organelle, named autophagoproteasome which is strongly induced by mTOR inhibitors in glioblastoma cells. Remarkably, when mTOR is maximally inhibited the proteasome component selectively moves within autophagy vacuoles, thus making the proteasome activity dependent on the entry within autophagy compartment.

  15. Vitamin K

    Science.gov (United States)

    Vitamins are substances that your body needs to grow and develop normally. Vitamin K helps your body by making proteins for ... blood clotting. If you don't have enough vitamin K, you may bleed too much. Newborns have ...

  16. Vitamin A

    Science.gov (United States)

    Vitamins are substances that your body needs to grow and develop normally. Vitamin A plays a role in your Vision Bone growth Reproduction Cell functions Immune system Vitamin A is an antioxidant. It can come from ...

  17. Vitamin C

    Science.gov (United States)

    Vitamins are substances that your body needs to grow and develop normally. Vitamin C is an antioxidant. It is important for ... promotes healing and helps the body absorb iron. Vitamin C comes from fruits and vegetables. Good sources ...

  18. Vitamin E

    Science.gov (United States)

    Vitamins are substances that your body needs to grow and develop normally. Vitamin E is an antioxidant. It plays a role ... immune system and metabolic processes. Good sources of vitamin E include Vegetable oils Margarine Nuts and seeds ...

  19. Vitamin D

    Science.gov (United States)

    Vitamins are substances that your body needs to grow and develop normally. Vitamin D helps your body absorb calcium. Calcium is ... main building blocks of bone. A lack of vitamin D can lead to bone diseases such as ...

  20. (D3)-bar and dS

    Energy Technology Data Exchange (ETDEWEB)

    Bergshoeff, Eric A. [Van Swinderen Institute for Particle Physics and Gravity,University of Groningen, Nijenborgh 4, 9747 AG Groningen (Netherlands); Dasgupta, Keshav [Ernest Rutherford Physics Building, McGill University,3600 University Street, Montréal QC, H3A 2T8 (Canada); Department of Physics, Stanford University,Stanford, CA 94305 (United States); Kallosh, Renata [Department of Physics, Stanford University,Stanford, CA 94305 (United States); Proeyen, Antoine Van [Instituut voor Theoretische Fysica, KU Leuven,Celestijnenlaan 200D, B-3001 Leuven (Belgium); Wrase, Timm [Institute for Theoretical Physics, TU Wien,Wiedner Hauptstr. 8-10, A-1040 Vienna (Austria)

    2015-05-12

    The role of the (D3)-bar brane in providing de Sitter vacua with spontaneously broken supersymmetry in the KKLT construction is clarified. The first step in this direction was explained in (http://dx.doi.org/10.1103/PhysRevD.68.046005, http://dx.doi.org/10.1088/1475-7516/2003/10/013): it was shown there that in the GKP background the bosonic contributions to the vacuum energy from the DBI and WZ term cancel for a D3 brane, but double for a (D3)-bar brane, leading to de Sitter vacua. The next step was taken in (http://dx.doi.org/10.1007/JHEP12(2014)117) where the analogous mechanism of the doubling (cancelation) of the (D3)-bar (D3) DBI and WZ terms was discovered in the presence of Volkov-Akulov fermions living on the brane, in a flat supergravity background. Here we confirm this mechanism of doubling/cancelation for the (D3)-bar /D3 brane in the GKP supergravity background preserving N=1, d=4 supersymmetry. We find that imaginary self-dual G{sub (3)} flux of type (2,1) nicely removes the SU(3) fermion triplet by giving it a large mass, while leaving the Volkov-Akulov goldstino, which is the SU(3) singlet, massless. This makes the de Sitter landscape in D-brane physics clearly related to de Sitter vacua in effective d=4 supergravity with a nilpotent multiplet and spontaneously broken supersymmetry.

  1. Vitamin D, sub-inflammation and insulin resistance. A window on a potential role for the interaction between bone and glucose metabolism.

    Science.gov (United States)

    Garbossa, Stefania Giuliana; Folli, Franco

    2017-06-01

    Vitamin D is a key hormone involved in the regulation of calcium/phosphorous balance and recently it has been implicated in the pathogenesis of sub-inflammation, insulin resistance and obesity. The two main forms of vitamin D are cholecalciferol (Vitamin D3) and ergocalciferol (Vitamin D2): the active form (1,25-dihydroxyvitamin D) is the result of two hydroxylations that take place in liver, kidney, pancreas and immune cells. Vitamin D increases the production of some anti-inflammatory cytokines and reduces the release of some pro-inflammatory cytokines. Low levels of Vitamin D are also associated with an up-regulation of TLRs expression and a pro-inflammatory state. Regardless of the effect on inflammation, Vitamin D seems to directly increase insulin sensitivity and secretion, through different mechanisms. Considering the importance of low grade chronic inflammation in metabolic syndrome, obesity and diabetes, many authors hypothesized the involvement of this nutrient/hormone in the pathogenesis of these diseases. Vitamin D status could alter the balance between pro and anti-inflammatory cytokines and thus affect insulin action, lipid metabolism and adipose tissue function and structure. Numerous studies have shown that Vitamin D concentrations are inversely associated with pro-inflammatory markers, insulin resistance, glucose intolerance and obesity. Interestingly, some longitudinal trials suggested also an inverse association between vitamin D status and incident type 2 diabetes mellitus. However, vitamin D supplementation in humans showed controversial effects: with some studies demonstrating improvements in insulin sensitivity, glucose and lipid metabolism while others showing no beneficial effect on glycemic control and on inflammation. In conclusion, although the evidences of a significant role of Vitamin D on inflammation, insulin resistance and insulin secretion in the pathogenesis of obesity, metabolic syndrome and type 2 diabetes, its potential

  2. Vitamin E

    Science.gov (United States)

    ... heart disease References Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academies Press. Washington, DC, 2000. ...

  3. Vitamin D content in human breast milk

    DEFF Research Database (Denmark)

    Við Streym, Susanna; Højskov, Carsten S; Møller, Ulla Kristine

    2016-01-01

    ) and cholecalciferol (vitamin D3) (vitamin D) and 25-hydroxivitamin D2 plus D3 (25-hydroxyvitamin D [25(OH)D]) in foremilk and hindmilk during the first 9 mo of lactation and identified indexes of importance to the concentrations. DESIGN: We collected blood and breast-milk samples from mothers at 2 wk (n = 107), 4 mo......, (n = 90), and 9 mo (n = 48) postpartum. Blood samples from infants were collected 4 and 9 mo after birth. We measured concentrations of vitamin D metabolites in blood and milk samples with the use of liquid chromatography-tandem mass spectrometry. RESULTS: Concentrations of vitamin D and 25(OH......)D concentrations (P taking vitamin D supplements had higher concentrations than did nonusers. Medians (IQRs) of infant daily intake through breast milk of vitamin D and 25(OH)D were 0.10 μg (0.02-0.40 μg) and 0.34 μg (0...

  4. [Vitamine D in patients with osteoporosis: sufficient or necessary?].

    Science.gov (United States)

    Ferrari, Serge

    2007-06-13

    Vitamin D is essential for intestinal calcium absorption, bone mineralisation and plays an important role in neuromuscular functions. Vitamin D insufficiency is highly prevalent among postmenopausal women with osteoporosis and in the elderly. In turn, supplements of vitamin D3 (cholecalciferol), and to a lesser extent vitamin D2 (ergocalciferol), may decrease falls and fracture risk by 25%. Despite some recent negative studies, the actual question is not to know whether vitamin D is necessary, but rather how much vitamin D is sufficient to prevent secondary hyperparathyroidism, falls and fractures. Moreover, the risk of osteoporosis and of fragility fractures may be influenced by genetic variation in the vitamin D receptor (VDR).

  5. Influence of vitamin D on cell cycle, apoptosis, and some apoptosis related molecules in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Nafise Tabasi

    2015-11-01

    Full Text Available Objective(s:Genetic and environmental factors are involved in the pathogenesis of systemic lupus erythematosus (SLE. Autoreactive lymphocytes are cleared through apoptosis and any disturbance in the apoptosis or clearance of apoptotic cells may disturb tolerance and lead to autoimmunity. Vitamin D has anti-proliferative effects and controls cell cycle progression. In this study we investigated the effects of vitamin D on cell cycle and apoptosis induction in lupus patients. Materials and Methods:Isolated peripheral blood mononuclear cells (PBMCs from 25 SLE patients were cultured in the presence of 50 nM of 1,25(OH2D3; then one part of the cells were stained with FITC labeled Annexin V and PI and were analyzed for apoptosis determination. For gene expression assessment of FasL, Bcl-2 and Bax, RNA was extracted from one another part of the cells, cDNA was synthesized and gene expression analysis was performed using Real time PCR. An additional part of the cells were treated with PI and the cell cycle was analyzed using flowcytometer. Results: The mean number of early apoptotic cells in vitamin D treated cells decreased significantly (18.48±7.9% compared to untreated cells (22.02±9.4% (P=0.008. Cell cycle analysis showed a significant increase in G1 phase in vitamin D treated cells (67.33±5.2% compared to non treated ones (60.77±5.7% (P =0.02. Vitamin D up-regulated the expression levels of Bcl-2 by (18.87 fold increase, and down-regulated expression of Bax (23% and FasL (25%. Conclusion:Vitamin D has regulatory effects on cell cycle progression, apoptosis and apoptosis related molecules in lupus patients.

  6. D=3 unification of curious supergravities

    Energy Technology Data Exchange (ETDEWEB)

    Duff, M.J. [Theoretical Physics, Blackett Laboratory, Imperial College London,London SW7 2AZ (United Kingdom); Mathematical Institute University of Oxford, Andrew Wiles Building,Woodstock Road, Radcliffe Observatory Quarter, Oxford, OX2 6GG (United Kingdom); Ferrara, S. [Theoretical Physics Department, CERN,CH-1211 Geneva (Switzerland); INFN - Laboratori Nazionali di Frascati,Via Enrico Fermi 40, I-00044 Frascati (Italy); Department of Physics and Astronomy andMani L. Bhaumik Institute for Theoretical Physics, UCLA,Los Angeles CA 90095-1547 (United States); Marrani, A. [Museo Storico della Fisica e Centro Studi e Ricerche “Enrico Fermi”,Via Panisperna 89A, I-00184, Roma (Italy); Dipartimento di Fisica e Astronomia “Galileo Galilei”,Università di Padova and INFN, Sez. di Padova,Via Marzolo 8, I-35131 Padova (Italy); Theoretical Physics Department, CERN,CH-1211 Geneva (Switzerland)

    2017-01-09

    We consider the dimensional reduction to D=3 of four maximal-rank supergravities which preserve minimal supersymmetry in D=11, 7, 5 and 4. Such “curious” theories were investigated some time ago, and the four-dimensional one corresponds to an N=1 supergravity with 7 chiral multiplets spanning the seven-disk manifold. Recently, this latter theory provided cosmological models for α-attractors, which are based on the disk geometry with possible restrictions on the parameter α. A unified picture emerges in D=3, where the Ehlers group of General Relativity merges with the S-, T- and U- dualities of the D=4 parent theories.

  7. D = 3 Unification of Curious Supergravities

    CERN Document Server

    Duff, M.J.; Marrani, A.

    2017-01-09

    We consider the dimensional reduction to D = 3 of four maximal-rank supergravities which preserve minimal supersymmetry in D = 11, 7, 5 and 4. Such "curious" theories were investigated some time ago, and the four-dimensional one corresponds to an N = 1 supergravity with 7 chiral multiplets spanning the seven-disk manifold. Recently, this latter theory was considered to provide cosmological models for alpha-attractors, which are based on the disk geometry with possible restrictions on the parameter alpha. A unified picture emerges in D = 3, where the Ehlers group of General Relativity merges with the S-, T- and U- dualities of the D = 4 parent theories.

  8. Vitamin D supplementation for prevention of mortality in adults

    DEFF Research Database (Denmark)

    Bjelakovic, Goran; Gluud, Lise Lotte; Nikolova, Dimitrinka

    2014-01-01

    Available evidence on the effects of vitamin D on mortality has been inconclusive. In a recent systematic review, we found evidence that vitamin D3 may decrease mortality in mostly elderly women. The present systematic review updates and reassesses the benefits and harms of vitamin D...... supplementation used in primary and secondary prophylaxis of mortality....

  9. SPARC is up-regulated during skeletal muscle regeneration and inhibits myoblast differentiation

    DEFF Research Database (Denmark)

    Petersson, Stine Juhl; Jørgensen, Louise Helskov; Andersen, Ditte C

    2013-01-01

    Skeletal muscle repair is mediated primarily by the muscle stem cell, the satellite cell. Several factors, including extracellular matrix, are known to regulate satellite cell function and regeneration. One factor, the matricellular Secreted Protein Acidic and Rich in Cysteine (SPARC) is highly up......-regulated during skeletal muscle disease, but its function remains elusive. In the present study, we demonstrate a prominent yet transient increase in SPARC mRNA and protein content during skeletal muscle regeneration that correlates with the expression profile of specific muscle factors like MyoD, Myf5, Myf6......, Myogenin, NCAM, CD34, and M-Cadherin, all known to be implicated in satellite cell activation/proliferation following muscle damage. This up regulation was detected in more cell types. Ectopic expression of SPARC in the muscle progenitor cell line C2C12 was performed to mimic the high levels of SPARC seen...

  10. Gene up-regulation in response to predator kairomones in the water flea, Daphnia pulex

    Directory of Open Access Journals (Sweden)

    Okada Yasukazu

    2010-04-01

    Full Text Available Abstract Background Numerous cases of predator-induced polyphenisms, in which alternate phenotypes are produced in response to extrinsic stimuli, have been reported in aquatic taxa to date. The genus Daphnia (Branchiopoda, Cladocera provides a model experimental system for the study of the developmental mechanisms and evolutionary processes associated with predator-induced polyphenisms. In D. pulex, juveniles form neckteeth in response to predatory kairomones released by Chaoborus larvae (Insecta, Diptera. Results Previous studies suggest that the timing of the sensitivity to kairomones in D. pulex can generally be divided into the embryonic and postembryonic developmental periods. We therefore examined which of the genes in the embryonic and first-instar juvenile stages exhibit different expression levels in the presence or absence of predator kairomones. Employing a candidate gene approach and identifying differentially-expressed genes revealed that the morphogenetic factors, Hox3, extradenticle and escargot, were up-regulated by kairomones in the postembryonic stage and may potentially be responsible for defense morph formation. In addition, the juvenile hormone pathway genes, JHAMT and Met, and the insulin signaling pathway genes, InR and IRS-1, were up-regulated in the first-instar stage. It is well known that these hormonal pathways are involved in physiological regulation following morphogenesis in many insect species. During the embryonic stage when morphotypes were determined, one of the novel genes identified by differential display was up-regulated, suggesting that this gene may be related to morphotype determination. Biological functions of the up-regulated genes are discussed in the context of defense morph formation. Conclusions It is suggested that, following the reception of kairomone signals, the identified genes are involved in a series of defensive phenotypic alterations and the production of a defensive phenotype.

  11. Neural cell adhesion molecule is a cardioprotective factor up-regulated by metabolic stress.

    OpenAIRE

    Nagao, Kazuya; Ono, Koh; Iwanaga, Yoshitaka; Tamaki, Yodo; Kojima, Yoji; Horie, Takahiro; Nishi, Hitoo; Kinoshita, Minako; Kuwabara, Yasuhide; Hasegawa, Koji; Kita, Toru; KIMURA, TAKESHI

    2010-01-01

    Screening for cell surface proteins up-regulated under stress conditions may lead to the identification of new therapeutic targets. To search for genes whose expression was enhanced by treatment with oligomycin, a mitochondrial-F(0)F(1) ATP synthase inhibitor, signal sequence trapping was performed in H9C2 rat cardiac myoblasts. One of the genes identified was that for neural cell adhesion molecule (NCAM, CD56), a major regulator of development, cell survival, migration, and neurite outgrowth...

  12. Rapid systemic up-regulation of genes after heat-wounding and electrical stimulation

    Science.gov (United States)

    Davies, E.; Vian, A.; Vian, C.; Stankovic, B.

    1997-01-01

    When one leaf of a tomato plant is electrically-stimulated or heat-wounded, proteinase inhibitor genes are rapidly up-regulated in distant leaves. The identity of the systemic wound signal(s) is not yet known, but major candidates include hormones transmitted via the phloem or the xylem, the electrically-stimulated self-propagating electrical signal in the phloem (the action potential, AP), or the heat-wound-induced surge in hydraulic pressure in the xylem evoking a local change in membrane potential in adjacent living cells (the variation potential, VP). In order to discriminate between these signals we have adopted two approaches. The first approach involves applying stimuli that evoke known signals and determining whether these signals have similar effects on the "model" transcripts for proteinase inhibitors (pin) and calmodulin (cal). Here we show that a heat wound almost invariably evokes a VP, while an electrical stimulation occasionally evokes an AP, and both of these signals induce accumulation of transcripts encoding proteinase inhibitors. The second approach involves identifying the array of genes turned on by heat-wounding. To this end, we have constructed a subtractive library for heat-wounded tissue, isolated over 800 putatively up-regulated clones, and shown that all but two of the fifty that we have analyzed by Northern hybridization are, indeed, up-regulated. Here we show the early kinetics of up-regulation of three of these transcripts in the terminal (4th) leaf in response to heat-wounding the 3rd leaf, about 5 cm away. Even though these transcripts show somewhat different time courses of induction, with one peaking at 30 min, another at 15 min, and another at 5 min after flaming of a distant leaf, they all exhibit a similar pattern, i.e., a transient period of transcript accumulation preceding a period of transcript decrease, followed by a second period of transcript accumulation.

  13. Up-regulation and clinical significance of serine protease kallikrein 6 in colon cancer.

    Science.gov (United States)

    Kim, Jong-Tae; Song, Eun Young; Chung, Kyung-Sook; Kang, Min Ah; Kim, Jae Wha; Kim, Sang Jick; Yeom, Young Il; Kim, Joo Heon; Kim, Kyo Hyun; Lee, Hee Gu

    2011-06-15

    Kallikrein-related peptidase 6 (KLK6) encodes a trypsin-like serine protease that is up-regulated in several cancers, although the putative functions of KLK6 in cancer have not been elucidated. In the current study, overexpression of KLK6 was identified in colon cancer, and the possibility that KLK6 may be a suitable candidate as a tumor marker was examined. Messenger RNA (mRNA) transcript levels and protein up-regulation of KLK6 in colon cancer tissues was examined using reverse transcriptase-polymerase chain reaction, immunohistochemistry, and clinicopathologic analyses. Cell proliferation, invasiveness, and antiapoptotic activity were determined in colon cancer cells that were transfected with small-interfering RNA (siRNA) of KLK6. KLK6 mRNA was up-regulated significantly in tumor tissues compared with nontumor regions. KLK6 protein was strongly expressed in adenocarcinomas but was not expressed in normal mucosa or in premalignant dysplastic lesions. Sera from patients with colon cancer revealed an increase in KLK6 secretion (0.25 μg/mL; P = .031) compared with noncancer cells (0.19 μg/mL). Clinicopathologic and immunohistochemical studies of 143 patients with colon cancer revealed a significant correlation between KLK6 expression and Dukes disease stage (P = .005). High KLK6 expression was associated significantly with shorter overall (P = .001) and recurrence-free survival (P = .001). The rates of proliferation and invasiveness were decreased by 50% in cells that were transfected with KLK6 siRNA. The overexpression of KLK6 led to decreased activity of the E-cadherin promoter. KLK6 was up-regulated significantly in tissues and sera from patients with colon cancer and was associated closely with a poor prognosis, suggesting that KLK6 may be used as a potential biomarker and a therapeutic target for colon cancer. Copyright © 2010 American Cancer Society.

  14. The Emerging Role of Vitamin D in Cancer Risk Reduction

    Science.gov (United States)

    2003-01-01

    dihydroxyvitamin D3 inhibits rat colon cancer development during the post initiation period (173). Both 1,25(OH)2D and a synthetic analog reduce...Akerstrom G. Reduced parathyroid vitamin D receptor messenger ribonucleic acid levels in primary and secondary hyperparathyroidism . J Clin...dietary vitamin D3 in rat colon carcinogenesis. Nutr Cancer 2000;38(1):65-73. 41. Holick MF. 1,25-Dihydroxyvitamin D3 and the skin: a unique

  15. Vitamin D compounds inhibit cancer stem-like cells and induce differentiation in triple negative breast cancer.

    Science.gov (United States)

    Shan, Naing Lin; Wahler, Joseph; Lee, Hong Jin; Bak, Min Ji; Gupta, Soumyasri Das; Maehr, Hubert; Suh, Nanjoo

    2017-10-01

    Triple-negative breast cancer is one of the least responsive breast cancer subtypes to available targeted therapies due to the absence of hormonal receptors, aggressive phenotypes, and the high rate of relapse. Early breast cancer prevention may therefore play an important role in delaying the progression of triple-negative breast cancer. Cancer stem cells are a subset of cancer cells that are thought to be responsible for tumor progression, treatment resistance, and metastasis. We have previously shown that vitamin D compounds, including a Gemini vitamin D analog BXL0124, suppress progression of ductal carcinoma in situ in vivo and inhibit cancer stem-like cells in MCF10DCIS mammosphere cultures. In the present study, the effects of vitamin D compounds in regulating breast cancer stem-like cells and differentiation in triple-negative breast cancer were assessed. Mammosphere cultures, which enriches for breast cancer cells with stem-like properties, were used to assess the effects of 1α,25(OH)2D3 and BXL0124 on cancer stem cell markers in the triple-negative breast cancer cell line, SUM159. Vitamin D compounds significantly reduced the mammosphere forming efficiency in primary, secondary and tertiary passages of mammospheres compared to control groups. Key markers of cancer stem-like phenotype and pluripotency were analyzed in mammospheres treated with 1α,25(OH)2D3 and BXL0124. As a result, OCT4, CD44 and LAMA5 levels were decreased. The vitamin D compounds also down-regulated the Notch signaling molecules, Notch1, Notch2, Notch3, JAG1, JAG2, HES1 and NFκB, which are involved in breast cancer stem cell maintenance. In addition, the vitamin D compounds up-regulated myoepithelial differentiating markers, cytokeratin 14 and smooth muscle actin, and down-regulated the luminal marker, cytokeratin 18. Cytokeratin 5, a biomarker associated with basal-like breast cancer, was found to be significantly down-regulated by the vitamin D compounds. These results suggest that

  16. Identification and analysis of Phytophthora cactorum genes up-regulated during cyst germination and strawberry infection.

    Science.gov (United States)

    Chen, Xiaoren; Klemsdal, Sonja Sletner; Brurberg, May Bente

    2011-10-01

    The oomycete Phytophthora cactorum can cause economically important diseases on numerous host plants worldwide, such as crown rot on strawberry. To explore the molecular mechanisms underlying the pathogenicity of P. cactorum on strawberry, transcriptional analysis of P. cactorum during strawberry infection and cyst germination was performed by applying suppression subtractive hybridization (SSH) and effector-specific differential display (ESDD) techniques. Two SSH cDNA libraries were generated, enriched for P. cactorum genes expressed during infection or during cyst germination, respectively, and 137 unique differentially expressed genes were identified. To specifically select RxLR effector genes from P. cactorum, ESDD was performed using RxLR and EER motif-based degenerate primers. Eight RxLR effector candidate genes as well as 67 other genes were identified out of 124 selected fragments. The expression levels of 20 putatively up-regulated genes were further analyzed using real-time RT-PCR, showing that, indeed 19 of these 20 genes were up-regulated during at least one of the studied developmental stages or during strawberry crown invasion, relative to the mycelium. This study provides a first overview of P. cactorum genes that are up-regulated immediately prior to or during strawberry infection and also provides a novel method for selecting RxLR effector genes from the unsequenced genome of P. cactorum.

  17. Gene and functional up-regulation of the BCRP/ABCG2 transporter in hepatocellular carcinoma.

    Science.gov (United States)

    Sukowati, Caecilia Hc; Rosso, Natalia; Pascut, Devis; Anfuso, Beatrice; Torre, Giuliano; Francalanci, Paola; Crocè, Lory S; Tiribelli, Claudio

    2012-11-15

    The Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of ABC transporters proteins super family responsible of drug resistance. Since data on ABCG2 expression in liver malignances are scanty, here we report the expression of ABCG2 in adult human hepatocellular carcinoma (HCC) in both in vivo and in vitro models with different degree of malignancy. In cell lines derived from human hepatocellular carcinoma, ABCG2 gene expression was assessed by reverse transcription quantitative real time PCR and function by Hoechst 33342 efflux assay; protein content was assessed by SDS-PAGE Western blot. ABCG2 expression was found to be highest in the most undifferentiated cell lines, and this was related with a higher functional activity. ABCG2 expression was sensitive to antineoplastic drugs since exposure to 5 μM doxorubicin for 24 hours resulted in significant up-regulations of ABCG2 in all cell lines, particularly in those lines with low basal ABCG2 expression (pexpression was also investigated in 51 adult liver tissues with HCC and related cirrhosis; normal liver tissue was used as control. ABCG2 gene expression was higher in HCC than both cirrhotic paired tissue and normal tissue. This up-regulation was greater (pexpression and differentiation stage both in human and HCC derived cell lines. The rapid up-regulation of ABCG2 to exposure to doxorubicin emphasizes the importance of this transporter in accounting for drug resistance in liver tumors.

  18. Netrin-1 up-regulation in inflammatory bowel diseases is required for colorectal cancer progression.

    Science.gov (United States)

    Paradisi, Andrea; Maisse, Carine; Coissieux, Marie-May; Gadot, Nicolas; Lépinasse, Florian; Delloye-Bourgeois, Céline; Delcros, Jean-Guy; Svrcek, Magali; Neufert, Clemens; Fléjou, Jean-François; Scoazec, Jean-Yves; Mehlen, Patrick

    2009-10-06

    Chronic inflammation and cancer are intimately associated. This is particularly true for inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, which show a major increased risk for colorectal cancer. While the understanding of the molecular pathogenesis of IBD has recently improved, the mechanisms that link these chronic inflammatory states to colorectal cancer development are in large part unknown. One of these mechanisms is NF-kappaB pathway activation which in turn may contribute to tumor formation by providing anti-apoptotic survival signals to the epithelial cells. Based on the observation that netrin-1, the anti-apoptotic ligand for the dependence receptors DCC and UNC5H is up-regulated in colonic crypts in response to NF-kappaB, we show here that colorectal cancers from inflammatory bowel diseases patients have selected up-regulation of netrin-1. Moreover, we demonstrate that this inflammation-driven netrin-1 up-regulation is causal for colorectal cancer development as interference with netrin-1 autocrine loop in a mouse model for ulcerative colitis-associated colorectal cancer, while showing no effect on inflammation, inhibits colorectal cancer progression.

  19. Hepatotoxicity of piperazine designer drugs: up-regulation of key enzymes of cholesterol and lipid biosynthesis.

    Science.gov (United States)

    Arbo, Marcelo Dutra; Melega, Simone; Stöber, Regina; Schug, Markus; Rempel, Eugen; Rahnenführer, Jörg; Godoy, Patricio; Reif, Raymond; Cadenas, Cristina; de Lourdes Bastos, Maria; Carmo, Helena; Hengstler, Jan G

    2016-12-01

    The piperazine derivatives most frequently consumed for recreational purposes are 1-benzylpiperazine, 1-(3,4-methylenedioxybenzyl) piperazine, 1-(3-trifluoromethylphenyl) piperazine and 1-(4-methoxyphenyl) piperazine. Generally, they are consumed as capsules, tablets or pills but also in powder or liquid forms. Currently, the precise mechanism by which piperazine designer drugs induce hepatotoxicity and whether they act by a common pathway is unclear. To answer this question, we performed a gene array study with rat hepatocytes incubated with the four designer drugs. Non-cytotoxic concentrations were chosen that neither induce a decrease in reduced glutathione or ATP depletion. Analysis of the gene array data showed a large overlap of gene expression alterations induced by the four drugs. This 'piperazine designer drug consensus signature' included 101 up-regulated and 309 down-regulated probe sets (p designer drugs. Regarding the down-regulated probe sets, only one gene was common to all four piperazine derivatives, the betaine-homocysteine-S-methyltransferase 2. Analysis of transcription factor binding sites of the 'piperazine designer drug consensus signature' identified the sterol regulatory element binding protein (SREBP-1) as strongly overrepresented in the up-regulated genes. SREBP transcription factors are known to regulate multiple genes of cholesterol metabolism. In conclusion, the present study shows that piperazine designer drugs act by up-regulating key enzymes of cholesterol biosynthesis which is likely to increase the risk of phospholipidosis and steatosis.

  20. Bimodal Influence of Vitamin D in Host Response to Systemic Candida Infection-Vitamin D Dose Matters

    NARCIS (Netherlands)

    Lim, J.H.N.; Ravikumar, S.; Wang, Y.M.; Thamboo, T.P.; Ong, L.; Chen, J.; Goh, J.G.; Tay, S.H.; Chengchen, L.; Win, M.S.; Leong, W.; Lau, T.; Foo, R.; Mirza, H.; Tan, K.S.; Sethi, S.; Khoo, A.L.; Chng, W.J.; Osato, M.; Netea, M.G.; Chai, L.Y.

    2015-01-01

    Vitamin D level is linked to susceptibility to infections, but its relevance in candidemia is unknown. We aimed to investigate the in vivo sequelae of vitamin D3 supplementation in systemic Candida infection. Implicating the role of vitamin D in Candida infections, we showed that candidemic patients

  1. Vitamin Chart

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Vitamin Chart KidsHealth / For Teens / Vitamin Chart Print en español Tabla de las vitaminas Type Benefits Sources Quantity Vitamin A Vitamin A prevents eye problems, promotes a ...

  2. Vitamin D: present and future.

    Science.gov (United States)

    Varsavsky, M; Alonso, G; García-Martín, A

    2014-10-01

    In recent years has been a growing interest by vitamin D, not only for its important role in the bone mineral metabolism, but also by the extra-osseous effects. Most of the scientific societies consider that deposits are sufficient if the serum concentration of 25-OH vitamin D is above 30ng/ml and are considered deficient if levels are below 20ng/ml. The majority of studies found that supplements of calcium plus vitamin D have a positive effect in reducing the risk of fracture and the risk of falls in the elderly, although several specifies that doses should be 700-1.000 IU daily. The treatment of the deficit can be performed with vitamin D2, D3 as well as calcidiol or the active metabolite calcitriol. In certain pathologies also selective vitamin D receptor activators can be used. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  3. 1, 25(OH)2D3 Inhibits Hepatocellular Carcinoma Development Through Reducing Secretion of Inflammatory Cytokines from Immunocytes

    OpenAIRE

    Guo, Jian; Ma, Zhenhua; Ma, Qingyong; Wu, Zheng; Fan, Ping; Zhou, Xiaojie; Chen, Lulu; Zhou, Shuang; Goltzman, David; Miao, Dengshun; Wu, Erxi

    2013-01-01

    Epidemiological and clinical studies have indicated that low vitamin D activity is not only associated with an increased cancer risk and a more aggressive tumor growth, but also connected with an aggravated liver damage caused by chronic inflammation. Meanwhile, increasing evidence has demonstrated that 1,25(OH)2D3 (the most biologically active metabolite of vitamin D) can inhibit inflammatory response in some chronic inflammatory associated cancer, which is considered to have the anti-tumor ...

  4. 1,25-Dihydroxyvitamin D3 inhibits cytokine production by human blood monocytes at the post-transcriptional level

    DEFF Research Database (Denmark)

    Müller, K; Haahr, P M; Diamant, M

    1992-01-01

    D3, and the synthetic analogue MC 903 ('Calcipotriol') were examined in parallel. 1,25-(OH)2D3 dose-dependently inhibited the production of IL-alpha, IL-6 and TNF-alpha by Escherichia coli lipopolysaccharide (LPS)-stimulated monocytes, without affecting superoxide production. MC 903 had comparable...... was not caused by impaired production of mRNA. Taken together, the study demonstrates a vitamin D-induced inhibitory effect of LPS-driven monokine production, which is most likely a vitamin D-receptor mediated phenomenon exerted at a post-transcriptional, presecretory level. Impaired monokine production may...

  5. Vitamin D-binding protein controls T cell responses to vitamin D

    DEFF Research Database (Denmark)

    Kongsbak, Martin; von Essen, Marina Rode; Levring, Trine Bøegh

    2014-01-01

    BACKGROUND: In vitro studies have shown that the active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), can regulate differentiation of CD4+ T cells by inhibiting Th1 and Th17 cell differentiation and promoting Th2 and Treg cell differentiation. However, the serum concentration of 1......,25(OH)2D3 is far below the effective concentration of 1,25(OH)2D3 found in in vitro studies, and it has been suggested that 1,25(OH)2D3 must be produced locally from the inactive precursor 25-hydroxyvitamin D3 (25(OH)D3) to affect ongoing immune responses in vivo. Although it has been reported...... that activated T cells express the 25(OH)D-1α-hydroxylase CYP27B1 that converts 25(OH)D3 to 1,25(OH)2D3, it is still controversial whether activated T cells have the capacity to produce sufficient amounts of 1,25(OH)2D3 to affect vitamin D-responsive genes. Furthermore, it is not known how the vitamin D...

  6. Mutations in BALB mitochondrial DNA induce CCL20 up-regulation promoting tumorigenic phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Sligh, James [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Janda, Jaroslav [University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Jandova, Jana, E-mail: jjandova@email.arizona.edu [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States)

    2014-11-15

    Highlights: • Alterations in mitochondrial DNA are commonly found in various human cancers. • Mutations in BALB mitochondrial DNA induce up-regulation of chemokine CCL20. • Increased growth and motility of mtBALB cells is associated with CCL20 levels. • mtDNA changes in BALB induce in vivo tumor growth through CCL20 up-regulation. • Mutations in mitochondrial DNA play important roles in keratinocyte neoplasia. - Abstract: mtDNA mutations are common in human cancers and are thought to contribute to the process of neoplasia. We examined the role of mtDNA mutations in skin cancer by generating fibroblast cybrids harboring a mutation in the gene encoding the mitochondrial tRNA for arginine. This somatic mutation (9821insA) was previously reported in UV-induced hyperkeratotic skin tumors in hairless mice and confers specific tumorigenic phenotypes to mutant cybrids. Microarray analysis revealed and RT-PCR along with Western blot analysis confirmed the up-regulation of CCL20 and its receptor CCR6 in mtBALB haplotype containing the mt-Tr 9821insA allele compared to wild type mtB6 haplotype. Based on reported role of CCL20 in cancer progression we examined whether the hyper-proliferation and enhanced motility of mtBALB haplotype would be associated with CCL20 levels. Treatment of both genotypes with recombinant CCL20 (rmCCL20) resulted in enhanced growth and motility of mtB6 cybrids. Furthermore, the acquired somatic alteration increased the in vivo tumor growth of mtBALB cybrids through the up-regulation of CCL20 since neutralizing antibody significantly decreased in vivo tumor growth of these cells; and tumors from anti-CCL20 treated mice injected with mtBALB cybrids showed significantly decreased CCL20 levels. When rmCCL20 or mtBALB cybrids were used as chemotactic stimuli, mtB6 cybrids showed increased motility while anti-CCL20 antibody decreased the migration and in vivo tumor growth of mtBALB cybrids. Moreover, the inhibitors of MAPK signaling and NF

  7. A physiologically based pharmacokinetic model of vitamin D ...

    Science.gov (United States)

    See attached 1. Please explain the nature of the study that resulted in this paper or presentation. This study presents an application of PBPK modeling to describe the formation of Vitamin D3. Recently, there has been a surge of interest in the health benefits of Vitamin D3, from heart health to cancer. Despite its importance, a PBPK model for Vitamin D3 does not exist in the literature. Due to its anti-inflammatory properties, Vitamin D3 is being prescribed to patients suffering diverse chronic illnesses. Because of its importance in several conditions, we thought it was important to understand its metabolic formation from precursors and distribution in the body. Time course data from the literature following the effect of oral supplementation in healthy adults was used to develop the first PBPK model for Vitamin D formation. 2. Why was this study done? The goal of this paper was to develop a PBPK model describing the metabolic formation of Vitamin D (as Vitamin D3) when receiving oral supplementation. In the process of developing the PBPK model, several novel concepts were used. For example, due to the extreme lipophilic nature of this vitamin (derived from cholesterol), partition coefficients were varied as a function of dose and time. Also, the regulation of enzymatic metabolism by its product (Vitamin D) was also examined. The result was a very different approach used, and a PBPK model that describes an essential vitamin in the body. 3. What is t

  8. Modulation of Mycobacterium bovis-Specific Responses of Bovine Peripheral Blood Mononuclear Cells by 1,25-Dihydroxyvitamin D3

    Science.gov (United States)

    Waters, W. R.; Nonnecke, B. J.; Rahner, T. E.; Palmer, M. V.; Whipple, D. L.; Horst, R. L.

    2001-01-01

    Historically, administration of vitamin D has been considered beneficial in the treatment of tuberculosis. The interaction of this vitamin {i.e., 1,25-dihdroxyvitamin D3 [1,25(OH)2D3]} with the antitubercular immune response, however, is not clear. In the present study, in vitro recall responses of peripheral blood mononuclear cells (PBMC) from cattle infected with Mycobacterium bovis were used to study the immune-modulatory effects of 1,25(OH)2D3 on M. bovis-specific responses in vitro. Addition of 1 or 10 nM 1,25(OH)2D3 inhibited M. bovis-specific proliferative responses of PBMC from M. bovis-infected cattle, affecting predominately the CD4+ cell subset. In addition, 1,25(OH)2D3 inhibited M. bovis-specific gamma interferon (IFN-γ) production yet enhanced M. bovis-specific nitric oxide (NO) production. Lymphocyte apoptosis, measured by flow cytometry using annexin-V staining, was diminished by addition of 1,25(OH)2D3 to PBMC cultures. These findings support the current hypothesis that 1,25(OH)2D3 enhances mycobacterial killing by increasing NO production, a potent antimicrobial mechanism of activated macrophages, and suggest that 1,25(OH)2D3 limits host damage by decreasing M. bovis-induced IFN-γ production. PMID:11687464

  9. 25-Hydroxyvitamin D3 1-Alpha-Hydroxylase-Dependent Stimulation of Renal Klotho Expression by Spironolactone

    Directory of Open Access Journals (Sweden)

    Ioana Alesutan

    2013-11-01

    Full Text Available Background: Klotho, a transmembrane protein, protease and hormone mainly expressed in kidney, is required for the suppression of 1,25(OH2D3-generating 25-hydroxyvitamin D3 1-alpha-hydroxylase (Cyp27b1 by FGF23. Conversely, 1,25(OH2D3 stimulates, by activating the vitamin D3 receptor (Vdr, the expression of klotho, thus establishing a negative feedback loop. Klotho protects against renal and vascular injury. Klotho deficiency accelerates aging and early death, effects at least partially due to excessive formation of 1,25(OH2D3 and subsequent hyperphosphatemia. Klotho expression is inhibited by aldosterone. The present study explored the interaction of aldosterone and DOCA as well as the moderately selective mineralocorticoid receptor antagonist spironolactone on klotho expression. Methods: mRNA levels were determined utilizing quantitative RT-PCR in human embryonic kidney cells (HEK293 or in renal tissues from mice without or with prior mineralocorticoid (aldosterone or DOCA and/or spironolactone treatment. In HEK293 cells, protein levels were determined by western blotting. The experiments in HEK293 cells were performed without or with silencing of CYP27B1, of vitamin D3 receptor (VDR or of mineralocorticoid receptor (NR3C2. Results: In HEK293 cells aldosterone and in mice DOCA significantly decreased KLOTHO gene expression, effects opposed by spironolactone treatment. Spironolactone treatment alone significantly increased KLOTHO and CYP27B1 transcript levels in HEK293 cells (24 hours and mice (8 hours or 5 days. Moreover, spironolactone significantly increased klotho and CYP27B1 protein levels in HEK293 cells (48 hours. Reduced NR3C2 expression following silencing did not significantly affect KLOTHO and CYP27B1 transcript levels in presence or absence of spironolactone. Silencing of CYP27B1 and VDR significantly blunted the stimulating effect of spironolactone on KLOTHO mRNA levels in HEK293 cells. Conclusion: Besides blocking the effects of

  10. The Natural Antimicrobial Enzyme Lysozyme is Up-Regulated in Gastrointestinal Inflammatory Conditions

    Directory of Open Access Journals (Sweden)

    Carlos A. Rubio

    2014-01-01

    Full Text Available The cells that line the mucosa of the human gastrointestinal tract (GI, that is, oral cavity, oesophagus, stomach, small intestine, large intestine, and rectum are constantly challenged by adverse micro-environmental factors, such as different pH, enzymes, and bacterial flora. With exception of the oral cavity, these microenvironments also contain remnant cocktails of secreted enzymes and bacteria from upper organs along the tract. The density of the GI bacteria varies, from 103/mL near the gastric outlet, to 1010/mL at the ileocecal valve, to 1011 to 1012/mL in the colon. The total microbial population (ca. 1014 exceeds the total number of cells in the tract. It is, therefore, remarkable that despite the prima facie inauspicious mixture of harmful secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To counteract the hostile microenvironment, the GI epithelia react by speeding cell exfoliation (the GI mucosa has a turnover time of two to three days, by increasing peristalsis, by eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial compounds, such as defensin-5 and lysozyme. Only recently, lysozyme was found up-regulated in Barrett’s oesophagitis, chronic gastritis, gluten-induced atrophic duodenitis (coeliac disease, collagenous colitis, lymphocytic colitis, and Crohn’s colitis. This up-regulation is a response directed to the special types of bacteria recently detected in these diseases. The aim of lysozyme up-regulation is to protect individual mucosal segments to chronic inflammation. The molecular mechanisms connected to the crosstalk between the intraluminal bacterial flora and the production of lysozyme released by the GI mucosae, are discussed. Bacterial resistance continues to exhaust our supply of commercial antibiotics. The potential use of lysozyme to treat infectious diseases is receiving much attention.

  11. Up-regulation of acyl-coenzyme A:cholesterol acyltransferase (ACAT) in nephrotic syndrome.

    Science.gov (United States)

    Vaziri, Nosratola D; Liang, Kaihui

    2002-05-01

    We have previously demonstrated that hypercholesterolemia in rats with puromycin-induced nephrotic syndrome (NS) is associated with up-regulation of hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and relative down-regulation of cholesterol 7alpha-hydroxylase (Ch-7alpha), which represent the rate-limiting steps in cholesterol biosynthesis and catabolism. Expression of HMG-CoA reductase is inhibited and Ch-7alpha is augmented by intracellular free cholesterol, which is avidly esterified by acyl-CoA:cholesterol acyltransferase (ACAT). Therefore, we hypothesized that NS may result in up-regulation of hepatic ACAT. Hepatic tissue ACAT mRNA (Northern blot), protein (Western blot) and enzymatic activity were determined in rats with puromycin-induced NS, placebo-treated control rats and Nagase hypoalbuminemic (NAG) rats. The NS group exhibited heavy proteinuria, hypoalbuminemia, normal creatinine clearance, severe hypercholesterolemia and hypertriglyceridemia. Despite severe hypoalbuminemia, NAG rats with inherited hypoalbuminemia exhibited only a mild elevation of plasma cholesterol and triglycerides. Severe hypercholesterolemia in the NS group was coupled with depressed liver tissue free cholesterol concentration and marked increases in hepatic ACAT mRNA, protein and enzymatic activity. In contrast, ACAT mRNA and protein contents of the liver were normal and ACAT activity was mildly elevated in the NAG group. NS results in marked up-regulation of hepatic ACAT, which is primarily due to proteinuria and not hypoalbuminemia, since the latter alone, as seen in NAG rats, does not significantly impact ACAT expression. Elevated ACAT in NS can contribute to dysregulation of cholesterol biosynthesis and catabolism by limiting the normal cholesterol signaling involved in regulation of these processes.

  12. Proteasome Inhibitor Up Regulates Liver Antioxidative Enzymes in Rat Model of Alcoholic Liver Disease

    Science.gov (United States)

    Bardag-Gorce, Fawzia; Oliva, Joan; Lin, Andrew; Li, Jun; French, Barbara A.; French, Samuel W.

    2010-01-01

    Oxidative stress occurs in the liver of rats fed alcohol chronically due to ethanol metabolism by CYP2E1, causing liver injury. The proteasome is considered as an antioxidant defense in the cell because of its activity in removing damaged and oxidized proteins, but a growing body of evidence shows that proteasome inhibitor treatment, at a non toxic low dose, provides protection against oxidative stress. In the present study, rats were fed ethanol for 4 weeks and were treated with the proteasome inhibitor PS-341 (Bortezomib, Velcade®). Exposure to proteasome inhibitor elicited the elevation of antioxidative defense by enhancing the levels of mRNA and protein expression transcripts of glutathione reductase (GSR), glutathione synthetase (GSS), glutathione peroxidase 2 (GPX2), and superoxide dismutase 2 (SOD2) in the liver of rats fed ethanol chronically, while ethanol alone did not increase these genes mRNA. Our results also showed that glutamate cysteine ligase catalytic subunit (GCLC), a rate-limiting enzyme in glutathione biosynthesis, was also up regulated in the liver of rats fed ethanol and injected with PS-431. Nrf2 mRNA level was significantly decreased in the liver of ethanol fed rats, as well as in the livers of animal fed ethanol and treated with proteasome inhibitor, indicating that the mechanism by which proteasome inhibitor up regulates the antioxidant response element is not due to regulation of Nrf2. However, ATF4, a major regulator of antioxidant response elements, was significantly up regulated by proteasome inhibitor treatment. The beneficial effects of proteasome inhibitor treatment also reside in the reversibility of the drug because the proteasome activity was significantly increased 72h post treatment. In conclusion, proteasome inhibitor treatment used at a non toxic low dose has potential protective effects against oxidative stress due to chronic ethanol feeding. PMID:21036165

  13. Neural cell adhesion molecule is a cardioprotective factor up-regulated by metabolic stress.

    Science.gov (United States)

    Nagao, Kazuya; Ono, Koh; Iwanaga, Yoshitaka; Tamaki, Yodo; Kojima, Yoji; Horie, Takahiro; Nishi, Hitoo; Kinoshita, Minako; Kuwabara, Yasuhide; Hasegawa, Koji; Kita, Toru; Kimura, Takeshi

    2010-06-01

    Screening for cell surface proteins up-regulated under stress conditions may lead to the identification of new therapeutic targets. To search for genes whose expression was enhanced by treatment with oligomycin, a mitochondrial-F(0)F(1) ATP synthase inhibitor, signal sequence trapping was performed in H9C2 rat cardiac myoblasts. One of the genes identified was that for neural cell adhesion molecule (NCAM, CD56), a major regulator of development, cell survival, migration, and neurite outgrowth in the nervous system. Immunohistochemical analyses in a mouse myocardial infarction model revealed that NCAM was strongly expressed in residual cardiac myocytes in the infarcted region. Increased expression of NCAM was also found during the remodeling period in a rat model of hypertension-induced heart failure. Lentivirus-mediated knockdown of NCAM decreased the cell growth and survival following oligomycin treatment in H9C2 cells. In primary rat neonatal cardiac myocytes, NCAM was also found to be up-regulated and played a protective role following oligomycin treatment. Analyses of downstream signaling revealed that knockdown of NCAM significantly decreased the basal AKT phosphorylation level. In contrast, NCAM mimetic peptide P2d activated AKT and significantly reduced oligomycin-induced cardiomyocyte death, which was abolished by treatment with the PI3K inhibitor LY-294002 as well as overexpression of the dominant-negative AKT mutant. These findings demonstrate that NCAM is a cardioprotective factor up-regulated under metabolic stress in cardiomyocytes and augmentation of this signal improved survival. (c) 2009 Elsevier Ltd. All rights reserved.

  14. Erbb2 up-regulation of ADAM12 expression accelerates skin cancer progression.

    Science.gov (United States)

    Rao, Velidi H; Vogel, Kristen; Yanagida, Jodi K; Marwaha, Nitin; Kandel, Amrit; Trempus, Carol; Repertinger, Susan K; Hansen, Laura A

    2015-10-01

    Solar ultraviolet (UV) radiation can cause severe damage to the skin and is the primary cause of most skin cancer. UV radiation causes DNA damage leading to mutations and also activates the Erbb2/HER2 receptor through indirect mechanisms involving reactive oxygen species. We hypothesized that Erbb2 activation accelerates the malignant progression of UV-induced skin cancer. Following the induction of benign squamous papillomas by UV exposure of v-ras(Ha) transgenic Tg.AC mice, mice were treated topically with the Erbb2 inhibitor AG825 and tumor progression monitored. AG825 treatment reduced tumor volume, increased tumor regression, and delayed the development of malignant squamous cell carcinoma (SCC). Progression to malignancy was associated with increased Erbb2 and ADAM12 (A Disintegin And Metalloproteinase 12) transcripts and protein, while inhibition of Erbb2 blocked the increase in ADAM12 message upon malignant progression. Similarly, human SCC and SCC cell lines had increased ADAM12 protein and transcripts when compared to normal controls. To determine whether Erbb2 up-regulation of ADAM12 contributed to malignant progression of skin cancer, Erbb2 expression was modulated in cultured SCC cells using forced over-expression or siRNA targeting, demonstrating up-regulation of ADAM12 by Erbb2. Furthermore, ADAM12 transfection or siRNA targeting revealed that ADAM12 increased both the migration and invasion of cutaneous SCC cells. Collectively, these results suggest Erbb2 up-regulation of ADAM12 as a novel mechanism contributing to the malignant progression of UV-induced skin cancer. Inhibition of Erbb2/HER2 reduced tumor burden, increased tumor regression, and delayed the progression of benign skin tumors to malignant SCC in UV-exposed mice. Inhibition of Erbb2 suppressed the increase in metalloproteinase ADAM12 expression in skin tumors, which in turn increased migration and tumor cell invasiveness. © 2014 Wiley Periodicals, Inc.

  15. Steroids up-regulate p66Shc longevity protein in growth regulation by inhibiting its ubiquitination.

    Directory of Open Access Journals (Sweden)

    Santosh Kumar

    2011-01-01

    Full Text Available p66Shc, an isoform of Shc adaptor proteins, mediates diverse signals, including cellular stress and mouse longevity. p66Shc protein level is elevated in several carcinomas and steroid-treated human cancer cells. Several lines of evidence indicate that p66Shc plays a critical role in steroid-related carcinogenesis, and steroids play a role in its elevated levels in those cells without known mechanism.In this study, we investigated the molecular mechanism by which steroid hormones up-regulate p66Shc protein level. In steroid-treated human prostate and ovarian cancer cells, p66Shc protein levels were elevated, correlating with increased cell proliferation. These steroid effects on p66Shc protein and cell growth were competed out by the respective antagonist. Further, actinomycin D and cyclohexamide could only partially block the elevated p66Shc protein level by steroids. Treatment with proteasomal inhibitors, but not lysosomal protease inhibitor, resulted in elevated p66Shc protein levels, even higher than that by steroids. Using prostate cancer cells as a model, immunoprecipitation revealed that androgens and proteasomal inhibitors reduce the ubiquitinated p66Shc proteins.The data collectively indicate that functional steroid receptors are required in steroid up-regulation of p66Shc protein levels in prostate and ovarian cancer cells, correlating with cell proliferation. In these steroid-treated cells, elevated p66Shc protein level is apparently in part due to inhibiting its ubiquitination. The results may lead to an impact on advanced cancer therapy via the regulation of p66Shc protein by up-regulating its ubiquitination pathway.

  16. Myostatin signaling is up-regulated in female patients with advanced heart failure.

    Science.gov (United States)

    Ishida, Junichi; Konishi, Masaaki; Saitoh, Masakazu; Anker, Markus; Anker, Stefan D; Springer, Jochen

    2017-07-01

    Myostatin, a negative regulator of skeletal muscle mass, is up-regulated in the myocardium of heart failure (HF) and increased myostatin is associated with weight loss in animal models with HF. Although there are disparities in pathophysiology and epidemiology between male and female patients with HF, it remains unclear whether there is gender difference in myostatin expression and whether it is associated with weight loss in HF patients. Heart tissue samples were collected from patients with advanced heart failure (n=31, female n=5) as well as healthy control donors (n=14, female n=6). Expression levels of myostatin and its related proteins in the heart were evaluated by western blotting analysis. Body mass index was significantly lower in female HF patients than in male counterparts (20.0±4.2 in female vs 25.2±3.8 in male, p=0.04). In female HF patients, both mature myostatin and pSmad2 were significantly up-regulated by 1.9 fold (p=0.05) and 2.5 fold (p<0.01) respectively compared to female donors, while expression of pSmad2 was increased by 2.8 times in male HF patients compared to male healthy subjects, but that of myostatin was not. There was no significant difference in protein expression related to myostatin signaling between male and female patients. In this study, myostatin and pSmad2 were significantly up-regulated in the failing heart of female patients, but not male patients, and female patients displayed lower body mass index. Enhanced myostatin signaling in female failing heart may causally contribute to pathogenesis of HF and cardiac cachexia. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Vitamin D: modulator of the immune system.

    Science.gov (United States)

    Baeke, Femke; Takiishi, Tatiana; Korf, Hannelie; Gysemans, Conny; Mathieu, Chantal

    2010-08-01

    1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the active form of vitamin D, is known to regulate calcium and phosphorus metabolism, thus being a key-player in bone-formation. However 1,25(OH)(2)D(3) also has a physiological role beyond its well-known role in skeletal homeostasis. Here, we describe 1,25(OH)(2)D(3) as an immunomodulator targeting various immune cells, including monocytes, macrophages, dendritic cells (DCs), as well as T-lymphocytes and B-lymphocytes, hence modulating both innate and adaptive immune responses. Besides being targets, immune cells express vitamin D-activating enzymes, allowing local conversion of inactive vitamin D into 1,25(OH)(2)D(3) within the immune system. Taken together, these data indicate that 1,25(OH)(2)D(3) plays a role in maintenance of immune homeostasis. Several epidemiological studies have linked inadequate vitamin D levels to a higher susceptibility of immune-mediated disorders, including chronic infections and autoimmune diseases. This review will discuss the complex immune-regulatory effects of 1,25(OH)(2)D(3) on immune cells as well as its role in infectious and autoimmune diseases, more in particular in tuberculosis and type 1 diabetes (T1D). Copyright 2010 Elsevier Ltd. All rights reserved.

  18. Utilization of Wind Turbines for Up-regulation of Power Grids

    DEFF Research Database (Denmark)

    Juelsgaard, Morten; Bendtsen, Jan Dimon; Wisniewski, Rafal

    2013-01-01

    of convex problems, where the load is distributed among several turbines in a farm. Thereafter, we present an optimization scheme that guarantees a lower limit for the overproduction period and subsequently propose an adaptive implementation that is robust against parameter uncertainties.......This work considers the use of wind turbines for aiding up-regulation of an electrical grid, by employing temporary overproduction with respect to available power. We present a simple model describing a turbine, and show how the possible period of overproduction can be maximized by solving a series...

  19. Hydrosoluble vitamins.

    Science.gov (United States)

    Chawla, Jasvinder; Kvarnberg, David

    2014-01-01

    The hydrosoluble vitamins are a group of organic substances that are required by humans in small amounts to prevent disorders of metabolism. Significant progress has been made in our understanding of the biochemical, physiologic and nutritional aspects of the water-soluble vitamins. Deficiency of these particular vitamins, most commonly due to inadequate nutrition, can result in disorders of the nervous system. Many of these disorders have been successfully prevented in developed countries; however, they are still common in developing countries. Of the hydrosoluble vitamins, the nervous system depends the most on vitamins B and C (ascorbic acid) for proper functioning. The B group vitamins include thiamin (vitamin B1), riboflavin (vitamin B2), niacin or niacinamide (vitamin B3), pantothenic acid (vitamin B5), pyridoxine or pyridoxal (vitamin B6) and cobalamin (vitamin B12). Clinical findings depend upon the deficiency of the underlying vitamin; generally, deficiency symptoms are seen from a combination rather than an isolated vitamin deficiency. True hereditary metabolic disorders and serious deficiency-associated diseases are rare and in general limited to particular geographic regions and high-risk groups. Their recognition is truly important as that determines the appropriate therapeutic management. The general availability of vitamins to practically everyone and several national health programs have saved many lives and prevented complications. However, there has been some apprehension for several decades about how harmless generous dosages of these vitamins are. Overt overdosages can cause vitamin toxicity affecting various body systems including the nervous system. Systemically, vitamin toxicity is associated with nonspecific symptoms, such as nausea, vomiting, diarrhea, and skin rash which are common with any acute or chronic vitamin overdose. At a national level, recommended daily allowances for vitamins become policy statements. Nutrition policy has far

  20. Vitamin D in plants: a review of occurrence, analysis, and biosynthesis

    DEFF Research Database (Denmark)

    Jäpelt, Rie Bak; Jakobsen, Jette

    2013-01-01

    The major function of vitamin D in vertebrates is maintenance of calcium homeostasis, but vitamin D insufficiency has also been linked to an increased risk of hypertension, autoimmune diseases, diabetes, and cancer. Therefore, there is a growing awareness about vitamin D as a requirement for opti......The major function of vitamin D in vertebrates is maintenance of calcium homeostasis, but vitamin D insufficiency has also been linked to an increased risk of hypertension, autoimmune diseases, diabetes, and cancer. Therefore, there is a growing awareness about vitamin D as a requirement...... for optimal health. Vitamin D3 is synthesized in the skin by a photochemical conversion of provitamin D3, but the necessary rays are only emitted all year round in places that lie below a 35° latitude. Unfortunately, very few food sources naturally contain vitamin D and the general population as a results...... fail to meet the requirements. Fish have the highest natural content of vitamin D expected to derive from an accumulation in the food chain originating from microalgae. Microalgae contain both vitamin D3 and provitamin D3, which suggests that vitamin D3 exist in the plant kingdom and vitamin D3 has...

  1. SYNTHESIS OF 25-HYDROXYVITAMIN D3 CONJUGATE WITH KEYHOLE LIMPET HEMOCYANIN AND OBTAINING OF IMMUNE SERA

    Directory of Open Access Journals (Sweden)

    А. O. Mazanova

    2015-08-01

    Full Text Available The study was aimed at obtaining polyclonal antibodies that recognize 25-Hydroxyvitamin D3, for their further specifications and applications in immunochemical test systems of 25-Hydroxyvitamin D3, determination in blood serum. We used the methods of chemical synthesis of immunoconjugates (modified carbodiimide method using N´-ethyl carbodiimide, thin layer chromatography, gel filtration and indirect immunoenzyme analysis ELISA. The work describes the stages of the synthesis of 25-Hydroxyvitamin D3, immunoconjugate with keyhole limpet hemocyanin (KLH, which was used for receiving immune sera. As a result of mouse and rabbit immunization antisera were obtained and antibody titers against 25-Hydroxyvitamin D3, were tested by immunoenzyme assay. It was demonstrated that the titer of specific antibodies was higher in rabbits compared with mice. The resulting polyclonal antibodies can be used for the development of immunochemical test systems for screening studies of 25-Hydroxyvitamin D3, content in human blood serum as a marker of vitamin D3 availability.

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

    Science.gov (United States)

    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. M2 macrophages promote beta-cell proliferation by up-regulation of SMAD7.

    Science.gov (United States)

    Xiao, Xiangwei; Gaffar, Iljana; Guo, Ping; Wiersch, John; Fischbach, Shane; Peirish, Lauren; Song, Zewen; El-Gohary, Yousef; Prasadan, Krishna; Shiota, Chiyo; Gittes, George K

    2014-04-01

    Determination of signaling pathways that regulate beta-cell replication is critical for beta-cell therapy. Here, we show that blocking pancreatic macrophage infiltration after pancreatic duct ligation (PDL) completely inhibits beta-cell proliferation. The TGFβ superfamily signaling inhibitor SMAD7 was significantly up-regulated in beta cells after PDL. Beta cells failed to proliferate in response to PDL in beta-cell-specific SMAD7 mutant mice. Forced expression of SMAD7 in beta cells by itself was sufficient to promote beta-cell proliferation in vivo. M2, rather than M1 macrophages, seem to be the inducers of SMAD7-mediated beta-cell proliferation. M2 macrophages not only release TGFβ1 to directly induce up-regulation of SMAD7 in beta cells but also release EGF to activate EGF receptor signaling that inhibits TGFβ1-activated SMAD2 nuclear translocation, resulting in TGFβ signaling inhibition. SMAD7 promotes beta-cell proliferation by increasing CyclinD1 and CyclinD2, and by inducing nuclear exclusion of p27. Our study thus reveals a molecular pathway to potentially increase beta-cell mass through enhanced SMAD7 activity induced by extracellular stimuli.

  4. Neural cell 3D microtissue formation is marked by cytokines' up-regulation.

    Directory of Open Access Journals (Sweden)

    Yinzhi Lai

    Full Text Available Cells cultured in three dimensional (3D scaffolds as opposed to traditional two-dimensional (2D substrates have been considered more physiologically relevant based on their superior ability to emulate the in vivo environment. Combined with stem cell technology, 3D cell cultures can provide a promising alternative for use in cell-based assays or biosensors in non-clinical drug discovery studies. To advance 3D culture technology, a case has been made for identifying and validating three-dimensionality biomarkers. With this goal in mind, we conducted a transcriptomic expression comparison among neural progenitor cells cultured on 2D substrates, 3D porous polystyrene scaffolds, and as 3D neurospheres (in vivo surrogate. Up-regulation of cytokines as a group in 3D and neurospheres was observed. A group of 13 cytokines were commonly up-regulated in cells cultured in polystyrene scaffolds and neurospheres, suggesting potential for any or a combination from this list to serve as three-dimensionality biomarkers. These results are supportive of further cytokine identification and validation studies with cells from non-neural tissue.

  5. Ski diminishes TGF-β1-induced myofibroblast phenotype via up-regulating Meox2 expression.

    Science.gov (United States)

    Chen, Zhaowei; Li, Wenjing; Ning, Yan; Liu, Tong; Shao, Jingxiang; Wang, Yaojun

    2014-12-01

    The aim of the present work was to investigate the mechanism of transforming growth factor (TGF)-β1 and Sloan-Kettering Institute (Ski) in the pathogenesis of hypertrophic scars (HS). Wound healing is an inherent process, but the aberrant wound healing of skin injury may lead to HS. There has been growing evidence suggesting a role for TGF-β1 and Ski in the pathogenesis of fibrosis. The MTT assay was used to detect the cell proliferation induced by TGF-β1. The Ski gene was transduced into cells with an adenovirus, and then the function of Ski in cell proliferation and differentiation was observed. Ski mRNA levels were measured by RT-PCR. Western blotting was used to detect the protein expression of α-SMA, E-cadherin, Meox1, Meox2, Zeb1 and Zeb2. TGF-β1 can promote human skin fibroblast (HSF) cell proliferation in a time-dependent manner, but the promoting effect could be suppressed by Ski. TGF-β1 also induces the formation of the myofibroblast phenotype and the effect of TGF-β1 could be diminished by Ski. Also, Ski modulates the cardiac myofibroblast phenotype and function through suppression of Zeb2 by up-regulating the expression of Meox2. Ski diminishes the myofibroblast phenotype induced by TGF-β1 through the suppression of Zeb2 by up-regulating the expression of Meox2. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Hypothalamic L-Histidine Decarboxylase Is Up-Regulated During Chronic REM Sleep Deprivation of Rats.

    Directory of Open Access Journals (Sweden)

    Gloria E Hoffman

    Full Text Available A competition of neurobehavioral drives of sleep and wakefulness occurs during sleep deprivation. When enforced chronically, subjects must remain awake. This study examines histaminergic neurons of the tuberomammillary nucleus of the posterior hypothalamus in response to enforced wakefulness in rats. We tested the hypothesis that the rate-limiting enzyme for histamine biosynthesis, L-histidine decarboxylase (HDC, would be up-regulated during chronic rapid eye movement sleep deprivation (REM-SD because histamine plays a major role in maintaining wakefulness. Archived brain tissues of male Sprague Dawley rats from a previous study were used. Rats had been subjected to REM-SD by the flowerpot paradigm for 5, 10, or 15 days. For immunocytochemistry, rats were transcardially perfused with acrolein-paraformaldehyde for immunodetection of L-HDC; separate controls used carbodiimide-paraformaldehyde for immunodetection of histamine. Immunolocalization of histamine within the tuberomammillary nucleus was validated using carbodiimide. Because HDC antiserum has cross-reactivity with other decarboxylases at high antibody concentrations, titrations localized L-HDC to only tuberomammillary nucleus at a dilution of ≥ 1:300,000. REM-SD increased immunoreactive HDC by day 5 and it remained elevated in both dorsal and ventral aspects of the tuberomammillary complex. Our results suggest that up-regulation of L-HDC within the tuberomammillary complex during chronic REM-SD may be responsible for maintaining wakefulness.

  7. Angiotensin II up-regulates monocarboxylate transporters expression in the rat adrenal gland.

    Science.gov (United States)

    Kirat, D; Shousha, S

    2016-01-11

    Angiotensin II (Ang II) is a major regulator of aldosterone secretion in the adrenal zona glomerulosa because it up-regulates the expression of a large number of genes involved in aldosterone biosynthesis. The transport of acetate across adrenocortical cells is a crucial step in the de novo synthesis of cholesterol, the steroid precursor of aldosterone. However, whether Ang II can affect this transport remains unknown. The current study aims to investigate the effect of in vivo infusion of Ang II on monocarboxylate transporters (MCT1, MCT2, and MCT4) gene expression in the rat adrenal gland. Immunohistochemical analysis and real-time PCR were used to examine the expression of MCTs at the protein and mRNA levels, respectively. The immunohistochemical analysis showed that higher numbers of cells expressed MCT1, MCT2, and MCT4 proteins in the zona glomerulosa and zona fasiculata of the adrenal cortex of Ang II-infused rats. Furthermore, real-time PCR indicated that in vivo infusion of Ang II increased the mRNA levels of MCT1, MCT2, and MCT4 in the rat adrenal gland. MCT up-regulation might maximize the intracellular transport of acetate in response to the stimulatory effect of Ang II on aldosterone secretion by the adrenal zona glomerulosa..

  8. Artemisia Extract Improves Insulin Sensitivity in Women With Gestational Diabetes Mellitus by Up-Regulating Adiponectin.

    Science.gov (United States)

    Sun, Xia; Sun, Hong; Zhang, Jing; Ji, Xianghong

    2016-12-01

    Gestational diabetes mellitus (GDM) has affected a great number of pregnant women worldwide. Artemisia extracts have been found to exhibit a potent antidiabetic effect in the treatment of type 2 diabetes mellitus. We aimed to examine the effects of Artemisia extract on insulin resistance and lipid profiles in pregnant GDM patients. Patients in their second trimester were randomly assigned to the Artemisia extract group (AE) or to a placebo group (PO). They were instructed to consume either AE or PO daily for a period of 10 weeks. Glucose and insulin profiles and adiponectin level were assessed at baseline (week 0) and after the treatment (week 10). Compared to the PO group, fasting plasma glucose, serum insulin levels, homeostasis model of assessment of insulin resistance (HOMA-IR), and β-cell function (HOMA-B) were significantly reduced in the AE group participants. Moreover, levels of circulating adiponectin were also significantly up-regulated in the AE group, which also positively contributed to improved insulin sensitivity. Daily administration of Artemisia extract improves insulin sensitivity by up-regulating adiponectin in women with gestational diabetes mellitus. © 2016, The American College of Clinical Pharmacology.

  9. Honey constituents up-regulate detoxification and immunity genes in the western honey bee Apis mellifera.

    Science.gov (United States)

    Mao, Wenfu; Schuler, Mary A; Berenbaum, May R

    2013-05-28

    As a managed pollinator, the honey bee Apis mellifera is critical to the American agricultural enterprise. Recent colony losses have thus raised concerns; possible explanations for bee decline include nutritional deficiencies and exposures to pesticides and pathogens. We determined that constituents found in honey, including p-coumaric acid, pinocembrin, and pinobanksin 5-methyl ether, specifically induce detoxification genes. These inducers are primarily found not in nectar but in pollen in the case of p-coumaric acid (a monomer of sporopollenin, the principal constituent of pollen cell walls) and propolis, a resinous material gathered and processed by bees to line wax cells. RNA-seq analysis (massively parallel RNA sequencing) revealed that p-coumaric acid specifically up-regulates all classes of detoxification genes as well as select antimicrobial peptide genes. This up-regulation has functional significance in that that adding p-coumaric acid to a diet of sucrose increases midgut metabolism of coumaphos, a widely used in-hive acaricide, by ∼60%. As a major component of pollen grains, p-coumaric acid is ubiquitous in the natural diet of honey bees and may function as a nutraceutical regulating immune and detoxification processes. The widespread apicultural use of honey substitutes, including high-fructose corn syrup, may thus compromise the ability of honey bees to cope with pesticides and pathogens and contribute to colony losses.

  10. Utrophin up-regulation by an artificial transcription factor in transgenic mice.

    Directory of Open Access Journals (Sweden)

    Elisabetta Mattei

    2007-08-01

    Full Text Available Duchenne Muscular Dystrophy (DMD is a severe muscle degenerative disease, due to absence of dystrophin. There is currently no effective treatment for DMD. Our aim is to up-regulate the expression level of the dystrophin related gene utrophin in DMD, complementing in this way the lack of dystrophin functions. To this end we designed and engineered several synthetic zinc finger based transcription factors. In particular, we have previously shown that the artificial three zinc finger protein named Jazz, fused with the appropriate effector domain, is able to drive the transcription of a test gene from the utrophin promoter "A". Here we report on the characterization of Vp16-Jazz-transgenic mice that specifically over-express the utrophin gene at the muscular level. A Chromatin Immunoprecipitation assay (ChIP demonstrated the effective access/binding of the Jazz protein to active chromatin in mouse muscle and Vp16-Jazz was shown to be able to up-regulate endogenous utrophin gene expression by immunohistochemistry, western blot analyses and real-time PCR. To our knowledge, this is the first example of a transgenic mouse expressing an artificial gene coding for a zinc finger based transcription factor. The achievement of Vp16-Jazz transgenic mice validates the strategy of transcriptional targeting of endogenous genes and could represent an exclusive animal model for use in drug discovery and therapeutics.

  11. Vitamin D Signaling Modulators in Cancer Therapy.

    Science.gov (United States)

    Luo, Wei; Johnson, Candace S; Trump, Donald L

    2016-01-01

    The antiproliferative and pro-apoptotic effects of 1α,25-dihydroxycholecalciferol (1,25(OH)2D3, 1,25D3, calcitriol) have been demonstrated in various tumor model systems in vitro and in vivo. However, limited antitumor effects of 1,25D3 have been observed in clinical trials. This may be attributed to a variety of factors including overexpression of the primary 1,25D3 degrading enzyme, CYP24A1, in tumors, which would lead to rapid local inactivation of 1,25D3. An alternative strategy for improving the antitumor activity of 1,25D3 involves the combination with a selective CYP24A1 inhibitor. The validity of this approach is supported by numerous preclinical investigations, which demonstrate that CYP24A1 inhibitors suppress 1,25D3 catabolism in tumor cells and increase the effects of 1,25D3 on gene expression and cell growth. Studies are now required to determine whether selective CYP24A1 inhibitors+1,25D3 can be used safely and effectively in patients. CYP24A1 inhibitors plus 1,25D3 can cause dose-limiting toxicity of vitamin D (hypercalcemia) in some patients. Dexamethasone significantly reduces 1,25D3-mediated hypercalcemia and enhances the antitumor activity of 1,25D3, increases VDR-ligand binding, and increases VDR protein expression. Efforts to dissect the mechanisms responsible for CYP24A1 overexpression and combinational effect of 1,25D3/dexamethasone in tumors are underway. Understanding the cross talk between vitamin D receptor (VDR) and glucocorticoid receptor (GR) signaling axes is of crucial importance to the design of new therapies that include 1,25D3 and dexamethasone. Insights gained from these studies are expected to yield novel strategies to improve the efficacy of 1,25D3 treatment. © 2016 Elsevier Inc. All rights reserved.

  12. Vitamin K

    Science.gov (United States)

    ... diabetes (Antidiabetes drugs)Vitamin K1 might decrease blood sugar. Diabetes medications are also used to lower blood sugar. Taking vitamin K1 along with diabetes medications might cause your blood sugar to go ...

  13. Vitamin D Receptor (VDR) Gene Polymorphisms (FokI, BsmI) and their Relation to Vitamin D Status in Pediatrics ��eta Thalassemia Major

    OpenAIRE

    Elhoseiny, Shereen Mohamed; Morgan, Dalia Saber; Rabie, Asmaa Mohamed; Bishay, Samer Tharwat

    2015-01-01

    Vitamin D is critical for calcium, phosphate homeostasis and for mineralization of the skeleton, especially during periods of rapid growth. Vitamin D Deficiency leads to rickets (in children) and osteomalacia (in adults). Expression and activation of the vitamin D receptor (VDR) are necessary for the effects of vitamin D, in which several single nucleotide polymorphisms have been identified especially (FokI, BsmI). In this study serum 25 (OH) vitamin D3 levels were estimated by Enzyme Linked ...

  14. Metabolic stability of 3-epi-1α,25-dihydroxyvitamin D3 over 1 α 25-dihydroxyvitamin D3: metabolism and molecular docking studies using rat CYP24A1.

    Science.gov (United States)

    Rhieu, Steve Y; Annalora, Andrew J; Wang, Guochun; Flarakos, Caroline C; Gathungu, Rose M; Vouros, Paul; Sigüeiro, Rita; Mouriño, Antonio; Schuster, Inge; Palmore, G Tayhas R; Reddy, G Satyanarayana

    2013-10-01

    3-epi-1α,25-dihydroxyvitamin D3 (3-epi-1α,25(OH)2D3), a natural metabolite of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), exhibits potent vitamin D receptor (VDR)-mediated actions such as inhibition of keratinocyte growth or suppression of parathyroid hormone secretion. These VDR-mediated actions of 3-epi-1α,25(OH)2D3 needed an explanation as 3-epi-1α,25(OH)2D3, unlike 1α,25(OH)2D3, exhibits low affinity towards VDR. Metabolic stability of 3-epi-1α,25(OH)2D3 over 1α,25(OH)2D3 has been hypothesized as a possible explanation. To provide further support for this hypothesis, we now performed comparative metabolism studies between 3-epi-1α,25(OH)2D3 and 1α,25(OH)2D3 using both the technique of isolated rat kidney perfusion and purified rat CYP24A1 in a cell-free reconstituted system. For the first time, these studies resulted in the isolation and identification of 3-epi-calcitroic acid as the final inactive metabolite of 3-epi-1α,25(OH)2D3 produced by rat CYP24A1. Furthermore, under identical experimental conditions, it was noted that the amount of 3-epi-calcitroic acid produced from 3-epi-1α,25(OH)2D3 is threefold less than that of calcitroic acid, the analogous final inactive metabolite produced from 1α,25(OH)2D3 . This key observation finally led us to conclude that the rate of overall side-chain oxidation of 3-epi-1α,25(OH)2D3 by rat CYP24A1 leading to its final inactivation is slower than that of 1α,25(OH)2D3. To elucidate the mechanism responsible for this important finding, we performed a molecular docking analysis using the crystal structure of rat CYP24A1. Docking results suggest that 3-epi-1α,25(OH)2D3, unlike 1α,25(OH)2D3, binds to CYP24A1 in an alternate configuration that destabilizes the formation of the enzyme-substrate complex sufficiently to slow the rate at which 3-epi-1α,25(OH)2D3 is inactivated by CYP24A1 through its metabolism into 3-epi-calcitroic acid. Copyright © 2013 Wiley Periodicals, Inc.

  15. Vitamin C

    Science.gov (United States)

    ... to stomach upset and diarrhea. Large doses of vitamin C supplementation are not recommended during pregnancy. They can lead ... gov/pubmed/23440782 . Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academies ...

  16. Quantizations of D = 3 Lorentz symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Lukierski, J. [University of Wroclaw, Institute for Theoretical Physics, Wroclaw (Poland); Tolstoy, V.N. [University of Wroclaw, Institute for Theoretical Physics, Wroclaw (Poland); Skobeltsyn Institute of Nuclear Physics, Lomonosov Moscow State University, Moscow (Russian Federation)

    2017-04-15

    Using the isomorphism o(3; C) ≅ sl(2; C) we develop a new simple algebraic technique for complete classification of quantum deformations (the classical r-matrices) for real forms o(3) and o(2,1) of the complex Lie algebra o(3; C) in terms of real forms of sl(2; C): su(2), su(1,1) and sl(2; R). We prove that the D = 3 Lorentz symmetry o(2,1) ≅ su(1,1) ≅ sl(2; R) has three different Hopf-algebraic quantum deformations, which are expressed in the simplest way by two standard su(1,1) and sl(2; R) q-analogs and by simple Jordanian sl(2; R) twist deformation. These quantizations are presented in terms of the quantum Cartan-Weyl generators for the quantized algebras su(1,1) and sl(2; R) as well as in terms of quantum Cartesian generators for the quantized algebra o(2,1). Finally, some applications of the deformed D = 3 Lorentz symmetry are mentioned. (orig.)

  17. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats.

    Directory of Open Access Journals (Sweden)

    Barbara D Boyan

    Full Text Available Osteoarthritis (OA in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OHD3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH2D3] accumulates in articular cartilage following injection of [3H]-25(OHD3. Previously, we showed that 24R,25(OH2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH2D3 in maintaining cartilage health. We examined the ability of 24R,25(OH2D3 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(OH2D3 or 1α,25(OH2D3. 24R,25(OH2D3 but not 1α,25(OH2D3 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(OH2D3 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(OH2D3 had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH2D3 protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis.

  18. Serum vitamin D metabolites in colorectal cancer patients receiving cholecalciferol supplementation: correlation with polymorphisms in the vitamin D genes.

    Science.gov (United States)

    Muindi, Josephia R; Adjei, Araba A; Wu, Zengru R; Olson, Isabel; Huang, Huayi; Groman, Adrienne; Tian, Lili; Singh, Prashant K; Sucheston, Lara E; Johnson, Candace S; Trump, Donald L; Fakih, Marwan G

    2013-08-01

    Cholecalciferol (D(3)) supplementation results in variable increases in serum 25(OH)D(3) levels, however, the influence of genetic polymorphisms on these variable responses is unclear. We measured serum 25(OH)D(3), 24,25(OH)(2)D(3), 1,25(OH)2D(3) and VDBP levels in 50 colorectal cancer (CRC) patients before and during 2,000 IU daily oral D(3) supplementation for six months and in 263 archived CRC serum samples. Serum PTH levels and PBMC 24-OHase activity were also measured during D(3) supplementation. TagSNPs in CYP2R1, CYP27A1, CYP27B1, CYP24A1, VDR, and GC genes were genotyped in all patients, and the association between these SNPs and serum vitamin D(3) metabolites levels before and after D(3) supplementation was analyzed. The mean baseline serum 25(OH)D(3) level was less than 32 ng/mL in 65 % of the 313 CRC patients. In the 50 patients receiving D(3) supplementation, serum levels of 25(OH)D(3) increased (p = 0.008), PTH decreased (p = 0.036) and 24,25(OH)(2)D(3), 1,25(OH)(2)D(3), VDBP levels and PBMC 24-OHase activity were unchanged. GC SNP rs222016 was associated with high 25(OH)D(3) and 1,25(OH)(2)D(3) levels at baseline while rs4588 and rs2282679 were associated with lower 25(OH)D(3) and 1,25(OH)(2)D(3) levels both before and after D(3) supplementation. CYP2R1 rs12794714 and rs10500804 SNPs were significantly associated with low 25(OH)D(3) levels after supplementation but not with baseline 25(OH)D(3). Our results show that D(3) supplementation increased 25(OH)D(3) levels in all patients. GC rs4588 and rs2283679 SNPs were associated with increased risk of vitamin D(3) insufficiency and suboptimal increase in 25(OH)D(3) levels after D(3) supplementation. Individuals with these genotypes may require higher D(3) supplementation doses to achieve vitamin D(3) sufficiency.

  19. Targeted delivery of 1,25-dihydroxyvitamin D3 to colon tissue and identification of a major 1,25-dihydroxyvitamin D3 glycoside from Solanumglaucophyllum plant leaves.

    Science.gov (United States)

    Zimmerman, Duane R; Koszewski, Nicholas J; Hoy, Derrel A; Goff, Jesse P; Horst, Ronald L

    2015-04-01

    the 1,3-diglycoside is one of the major forms of 1,25D3 found in the leaf. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Autophagy up-regulation by early weaning in the liver, spleen and skeletal muscle of piglets.

    Science.gov (United States)

    Zhang, Shaojin; Li, Xiao; Li, Lei; Yan, Xianghua

    2011-07-01

    Autophagy, a catabolic process responsible for the degradation of cytosolic components and the preservation of cellular homeostasis in virtually all eukaryotic organisms, is up-regulated when nutrient supplies are limited. However, whether early weaning induces autophagy in infants is not completely clear. In the present study, we used piglets as the early-weaning model to examine the autophagic activity in different tissues in response to nutrient status. Western blot analysis demonstrated that microtubule-associated protein 1 light chain 3-II, a promising marker protein for macroautophagy, was expressed at a notably higher level at 12 and 24 h weaning treatments than without weaning treatment (P weaning treatments (P early weaning may be helpful for the physiological system, which controls the balance of energy and nutrients for basic cell functions in the piglet model.

  1. Lipopolysaccharide-induced pulpitis up-regulates TRPV1 in trigeminal ganglia.

    Science.gov (United States)

    Chung, M-K; Lee, J; Duraes, G; Ro, J Y

    2011-09-01

    Tooth pain often accompanies pulpitis. Accumulation of lipopolysaccharides (LPS), a product of Gram-negative bacteria, is associated with painful clinical symptoms. However, the mechanisms underlying LPS-induced tooth pain are not clearly understood. TRPV1 is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and hyperalgesia under inflammation or injury. Although TRPV1 is expressed in pulpal afferents, it is not known whether the application of LPS to teeth modulates TRPV1 in trigeminal nociceptors. By assessing the levels of protein and transcript of TRPV1 in mouse trigeminal ganglia, we demonstrate that dentinal application of LPS increases the expression of TRPV1. Our results suggest that the up-regulation of TRPV1 in trigeminal nociceptors following bacterial infection could contribute to hyperalgesia under pulpitis conditions.

  2. Axl receptor tyrosine kinase is up-regulated in metformin resistant prostate cancer cells.

    Science.gov (United States)

    Bansal, Nitu; Mishra, Prasun J; Stein, Mark; DiPaola, Robert S; Bertino, Joseph R

    2015-06-20

    Recent epidemiological studies showed that metformin, a widely used anti-diabetic drug might prevent certain cancers. Metformin also has an anti-proliferative effect in preclinical studies of both hematologic malignancies as well as solid cancers and clinical studies testing metformin as an anti-cancer drug are in progress. However, all cancer types do not respond to metformin with the same effectiveness or acquire resistance. To understand the mechanism of acquired resistance and possibly its mechanism of action as an anti-proliferative agent, we developed metformin resistant LNCaP prostate cancer cells. Metformin resistant LNCaP cells had an increased proliferation rate, increased migration and invasion ability as compared to the parental cells, and expressed markers of epithelial-mesenchymal transition (EMT). A detailed gene expression microarray comparing the resistant cells to the wild type cells revealed that Edil2, Ereg, Axl, Anax2, CD44 and Anax3 were the top up-regulated genes and calbindin 2 and TPTE (transmembrane phosphatase with tensin homology) and IGF1R were down regulated. We focused on Axl, a receptor tyrosine kinase that has been shown to be up regulated in several drug resistance cancers. Here, we show that the metformin resistant cell line as well as castrate resistant cell lines that over express Axl were more resistant to metformin, as well as to taxotere compared to androgen sensitive LNCaP and CWR22 cells that do not overexpress Axl. Forced overexpression of Axl in LNCaP cells decreased metformin and taxotere sensitivity and knockdown of Axl in resistant cells increased sensitivity to these drugs. Inhibition of Axl activity by R428, a small molecule Axl kinase inhibitor, sensitized metformin resistant cells that overexpressed Axl to metformin. Inhibitors of Axl may enhance tumor responses to metformin and other chemotherapy in cancers that over express Axl.

  3. Up-Regulated Expression of Matrix Metalloproteinases in Endothelial Cells Mediates Platelet Microvesicle-Induced Angiogenesis.

    Science.gov (United States)

    Sun, Cheng; Feng, Shi-Bin; Cao, Zheng-Wang; Bei, Jun-Jie; Chen, Qiang; Zhao, Wei-Bo; Xu, Xian-Jie; Zhou, Zhou; Yu, Zheng-Ping; Hu, Hou-Yuan

    2017-01-01

    Platelet microvesicles (PMVs) contribute to angiogenesis and vasculogenesis, but the mechanisms underlying these contributions have not been fully elucidated. In the present study, we investigated whether PMVs regulate the angiogenic properties of endothelial cells (ECs) via mechanisms extending beyond the transport of angiogenic regulators from platelets. In vitro Matrigel tube formation assay and in vivo Matrigel plug assay were used to evaluate the pro-angiogenic activity of PMVs. The effects of PMVs on the migration of human umbilical vein endothelial cells (HUVECs) were detected by transwell assay and wound-healing assay. Real-time PCR and western blot were conducted to examine mRNA and protein expression of pro-angiogenic factors in HUVECs. Matrix metalloproteinase (MMP) activity was assayed by gelatin zymography. Moreover, the effects of specific MMP inhibitors were tested. PMVs promoted HUVEC capillary-like network formation in a dose-dependent manner. Meanwhile, PMVs dose-dependently facilitated HUVEC migration. Levels of MMP-2 and MMP-9 expression and activity were up-regulated in HUVECs stimulated with PMVs. Inhibition of MMPs decreased their pro-angiogenic and pro-migratory effects on HUVECs. Moreover, we confirmed the pro-angiogenic activity of PMVs in vivo in mice with subcutaneous implantation of Matrigel, and demonstrated that blockade of MMPs attenuated PMV-induced angiogenesis. The findings of our study indicate that PMVs promote angiogenesis by up-regulating MMP expression in ECs via mechanism extending beyond the direct delivery of angiogenic factors. © 2017 The Author(s). Published by S. Karger AG, Basel.

  4. A-to-I RNA Editing Up-regulates Human Dihydrofolate Reductase in Breast Cancer.

    Science.gov (United States)

    Nakano, Masataka; Fukami, Tatsuki; Gotoh, Saki; Nakajima, Miki

    2017-03-24

    Dihydrofolate reductase (DHFR) plays a key role in folate metabolism and is a target molecule of methotrexate. An increase in the cellular expression level of DHFR is one of the mechanisms of tumor resistance to methotrexate. The present study investigated the possibility that adenosine-to-inosine RNA editing, which causes nucleotide conversion by adenosine deaminase acting on RNA (ADAR) enzymes, might modulate DHFR expression. In human breast adenocarcinoma-derived MCF-7 cells, 26 RNA editing sites were identified in the 3'-UTR of DHFR. Knockdown of ADAR1 decreased the RNA editing levels of DHFR and resulted in a decrease in the DHFR mRNA and protein levels, indicating that ADAR1 up-regulates DHFR expression. Using a computational analysis, miR-25-3p and miR-125a-3p were predicted to bind to the non-edited 3'-UTR of DHFR but not to the edited sequence. The decrease in DHFR expression by the knockdown of ADAR1 was restored by transfection of antisense oligonucleotides for these miRNAs, suggesting that RNA editing mediated up-regulation of DHFR requires the function of these miRNAs. Interestingly, we observed that the knockdown of ADAR1 decreased cell viability and increased the sensitivity of MCF-7 cells to methotrexate. ADAR1 expression levels and the RNA editing levels in the 3'-UTR of DHFR in breast cancer tissues were higher than those in adjacent normal tissues. Collectively, the present study demonstrated that ADAR1 positively regulates the expression of DHFR by editing the miR-25-3p and miR-125a-3p binding sites in the 3'-UTR of DHFR, enhancing cellular proliferation and resistance to methotrexate. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Up-regulated expression of extracellular matrix remodeling genes in phagocytically challenged trabecular meshwork cells.

    Directory of Open Access Journals (Sweden)

    Kristine M Porter

    Full Text Available Cells in the trabecular meshwork (TM, the tissue responsible for draining aqueous humor out of the eye, are known to be highly phagocytic. Phagocytic function in TM cells is thought to play an important role in the normal functioning of the outflow pathway. Dysfunction of phagocytosis could lead to abnormalities of outflow resistance and increased intraocular pressure (IOP. However, the molecular mechanisms triggered by phagocytosis in TM cells are completely unknown.Gene expression profile analysis of human TM cells phagocytically challenged to E. coli or pigment under physiological and oxidative stress environment were performed using Affymetrix U133 plus 2.0 array and analyzed with Genespring GX. Despite the differential biological response elicited by E. coli and pigment particles, a number of genes, including MMP1, MMP3, TNFSF11, DIO2, KYNU, and KCCN2 showed differential expression with both phagocytic ligands in all conditions. Data was confirmed by qPCR in both human and porcine TM cells. Metacore pathway analysis and the usage of recombinant adenovirus encoding the dominant negative mutant of IkB identified NF-κB as a transcription factor mediating the up-regulation of at least MMP1 and MMP3 in TM cells with phagocytosis. In-gel zymography demonstrated increased collagenolytic and caseinolytic activities in the culture media of TM cells challenge to E. coli. In addition, collagenolytic I activity was further confirmed using the self-quenched fluorescent substrate DQ-Collagen I.Here we report for the first time the differential gene expression profile of TM cells phagocytically challenged with either E. coli or pigment. Our data indicate a potential role of phagocytosis in outflow pathway tissue homeostasis through the up-regulation and/or proteolytic activation of extracellular matrix remodeling genes.

  6. Propofol up-regulates Mas receptor expression in dorsal root ganglion neurons.

    Science.gov (United States)

    Cao, Lijun; Xun, Junmei; Jiang, Xinghua; Tan, Rong

    2013-08-01

    Mas is a functional binding site for angiotensin (Ang)-(1-7), a critical component of the renin-angiotensin system that is involved in processing nociceptive information. A recent study reported the localization of Mas in rat dorsal root ganglia (DRG) and demonstrated that Ang-(1-7) produced a dose-dependent peripheral antinociceptive effect in rats through the Mas receptor by an opioid-independent mechanism. In the present study, we for the first time examined the effect of propofol on Mas expression in cultured DRG neurons. We treated rat DRG neurons with propofol at different concentrations (0.1, 0.5, 1, 5 or 10 microM) for different length of time (0.5, 1, 2, 4 or 6 h) with or without transcription inhibitor actinomycin D or different kinase inhibitors. Propofol increased the Mas receptormRNA level in a statistically significant dose- and time-dependent manner within 4 h, which led to dose-dependent up-regulation of the Mas receptor protein level as well as Ang-(1-7) binding on the cell membrane. Actinomycin D (1 mg/ml) and p38 mitogen-activated protein kinase inhibitor PD169316 (25 microM) completely abolished the effect of propofol on Mas receptor expression in DRG neurons. In conclusion, we demonstrate that propofol markedly up-regulates Mas receptor expression at the transcription level in DRG neurons by a p38 MAPK-dependent mechanism. This study provides new insights into the mechanisms of action of propofol in peripheral antinociception, and suggests a new regulatory mechanism on the Ang-(1-7)/Mas axis in the peripheral nervous system.

  7. Rapamycin up-regulates triglycerides in hepatocytes by down-regulating Prox1.

    Science.gov (United States)

    Kwon, Sora; Jeon, Ji-Sook; Kim, Su Bin; Hong, Young-Kwon; Ahn, Curie; Sung, Jung-Suk; Choi, Inho

    2016-02-27

    Although the prolonged use of rapamycin may cause unwanted side effects such as hyperlipidemia, the underlying mechanism remains unknown. Prox1 is a transcription factor responsible for the development of several tissues including lymphatics and liver. There is growing evidences that Prox1 participates in metabolism in addition to embryogenesis. However, whether Prox1 is directly related to lipid metabolism is currently unknown. HepG2 human hepatoma cells were treated with rapamycin and total lipids were analyzed by thin layer chromatography. The effect of rapamycin on the expression of Prox1 was determined by western blotting. To investigate the role of Prox1 in triglycerides regulation, siRNA and overexpression system were employed. Rapamycin was injected into mice for 2 weeks and total lipids and proteins in liver were measured by thin layer chromatography and western blot analysis, respectively. Rapamycin up-regulated the amount of triglyceride and down-regulated the expression of Prox1 in HepG2 cells by reducing protein half-life but did not affect its transcript. The loss-of-function of Prox1 was coincident with the increase of triglycerides in HepG2 cells treated with rapamycin. The up-regulation of triglycerides by rapamycin in HepG2 cells reverted to normal levels by the compensation of Prox1 using the overexpression system. Rapamycin also down-regulated Prox1 expression but increased triglycerides in mouse liver. This study suggests that rapamycin can increase the amount of triglycerides by down-regulating Prox1 expression in hepatocytes, which means that the mammalian target of rapamycin (mTOR) signaling is important for the regulation of triglycerides by maintaining Prox1 expression.

  8. Smoking-mediated up-regulation of GAD67 expression in the human airway epithelium.

    Science.gov (United States)

    Wang, Guoqing; Wang, Rui; Ferris, Barbara; Salit, Jacqueline; Strulovici-Barel, Yael; Hackett, Neil R; Crystal, Ronald G

    2010-10-29

    The production of gamma-amino butyric acid (GABA) is dependent on glutamate decarboxylases (GAD65 and GAD67), the enzymes that catalyze the decarboxylation of glutamate to GABA. Based on studies suggesting a role of the airway epithelial GABAergic system in asthma-related mucus overproduction, we hypothesized that cigarette smoking, another disorder associated with increased mucus production, may modulate GABAergic system-related gene expression levels in the airway epithelium. We assessed expression of the GABAergic system in human airway epithelium obtained using bronchoscopy to sample the epithelium and microarrays to evaluate gene expression. RT-PCR was used to confirm gene expression of GABAergic system gene in large and small airway epithelium from heathy nonsmokers and healthy smokers. The differences in the GABAergic system gene was further confirmed by TaqMan, immunohistochemistry and Western analysis. The data demonstrate there is a complete GABAergic system expressed in the large and small human airway epithelium, including glutamate decarboxylase, GABA receptors, transporters and catabolism enzymes. Interestingly, of the entire GABAergic system, smoking modified only the expression of GAD67, with marked up-regulation of GAD67 gene expression in both large (4.1-fold increase, p smoking. In the context that GAD67 is the rate limiting enzyme in GABA synthesis, the correlation of GAD67 gene expression with MUC5AC expressions suggests that the up-regulation of airway epithelium expression of GAD67 may contribute to the increase in mucus production observed in association with cigarette smoking. NCT00224198; NCT00224185.

  9. Low-level laser irradiation stimulates tenocyte migration with up-regulation of dynamin II expression.

    Directory of Open Access Journals (Sweden)

    Wen-Chung Tsai

    Full Text Available Low-level laser therapy (LLLT is commonly used to treat sports-related tendinopathy or tendon injury. Tendon healing requires tenocyte migration to the repair site, followed by proliferation and synthesis of the extracellular matrix. This study was designed to determine the effect of laser on tenocyte migration. Furthermore, the correlation between this effect and expression of dynamin 2, a positive regulator of cell motility, was also investigated. Tenocytes intrinsic to rat Achilles tendon were treated with low-level laser (660 nm with energy density at 1.0, 1.5, and 2.0 J/cm(2. Tenocyte migration was evaluated by an in vitro wound healing model and by transwell filter migration assay. The messenger RNA (mRNA and protein expressions of dynamin 2 were determined by reverse transcription/real-time polymerase chain reaction (real-time PCR and Western blot analysis respectively. Immunofluorescence staining was used to evaluate the dynamin 2 expression in tenocytes. Tenocytes with or without laser irradiation was treated with dynasore, a dynamin competitor and then underwent transwell filter migration assay. In vitro wound model revealed that more tenocytes with laser irradiation migrated across the wound border to the cell-free zone. Transwell filter migration assay confirmed that tenocyte migration was enhanced dose-dependently by laser. Real-time PCR and Western-blot analysis demonstrated that mRNA and protein expressions of dynamin 2 were up-regulated by laser irradiation dose-dependently. Confocal microscopy showed that laser enhanced the expression of dynamin 2 in cytoplasm of tenocytes. The stimulation effect of laser on tenocytes migration was suppressed by dynasore. In conclusion, low-level laser irradiation stimulates tenocyte migration in a process that is mediated by up-regulation of dynamin 2, which can be suppressed by dynasore.

  10. Vitamine D analogue-based therapies for psoriasis.

    Science.gov (United States)

    O'Neill, J L; Feldman, S R

    2010-05-01

    Topical vitamin D3 analogues are a mainstay of treatment in mild to moderate plaque psoriasis. Vitamin D3 analogues exert their effect in psoriasis via binding nuclear vitamin D3 receptors on genes involved in cellular proliferation, differentiation and inflammation. Currently available synthetic vitamin D3 analogues include calcipotriol, maxacalcitol, tacalcitol and calcitriol. These agents are only minimally systemically absorbed and therefore have few systemic side effects. Local irritation is the most frequently noted side effect and can be managed by combining vitamin D3 analogues with other topical or systemic therapies, such as topical corticosteroids or narrow-band UVB phototherapy. The use of a vitamin D agent helps improve the efficacy of topical corticosteroids for psoriasis and helps minimize the potential for adverse events associated with topical corticosteroid treatment. Care should be taken when combining with other topical therapies due to potential inactivation of either agent. Topical vitamin D3 analogues can be a cost-effective addition to a psoriasis treatment regimen, especially when compliance is encouraged by the tolerability of these agents and more costly systemic agents are avoided. Copyright (c) 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

  11. Insecticide-Mediated Up-Regulation of Cytochrome P450 Genes in the Red Flour Beetle (Tribolium castaneum

    Directory of Open Access Journals (Sweden)

    Xiao Liang

    2015-01-01

    Full Text Available Some cytochrome P450 (CYP genes are known for their rapid up-regulation in response to insecticide exposures in insects. To date, however, limited information is available with respect to the relationships among the insecticide type, insecticide concentration, exposure duration and the up-regulated CYP genes. In this study, we examined the transcriptional response of eight selected CYP genes, including CYP4G7, CYP4Q4, CYP4BR3, CYP12H1, CYP6BK11, CYP9D4, CYP9Z5 and CYP345A1, to each of four insecticides in the red flour beetle, Tribolium castaneum. Reverse transcription quantitative PCR (RT-qPCR revealed that CYP4G7 and CYP345A1 can be significantly up-regulated by cypermethrin (1.97- and 2.06-fold, respectively, permethrin (2.00- and 2.03-fold and lambda-cyhalothrin (1.73- and 1.81-fold, whereas CYP4BR3 and CYP345A1 can be significantly up-regulated by imidacloprid (1.99- and 1.83-fold when 20-day larvae were exposed to each of these insecticides at the concentration of LC20 for 24 h. Our studies also showed that similar levels of up-regulation can be achieved for CYP4G7, CYP4BR3 and CYP345A1 by cypermethrin, permethrin, lambda-cyhalothrin or imidacloprid with approximately one fourth of LC20 in 6 h. Our study demonstrated that up-regulation of these CYP genes was rapid and only required low concentrations of insecticides, and the up-regulation not only depended on the CYP genes but also the type of insecticides. Our results along with those from previous studies also indicated that there were no specific patterns for predicting the up-regulation of specific CYP gene families based on the insecticide classification.

  12. Vitamin D deficiency decreases survival of bacterial meningoencephalitis in mice.

    Science.gov (United States)

    Djukic, Marija; Sostmann, Nadine; Bertsch, Thomas; Mecke, Marianne; Nessler, Stefan; Manig, Anja; Hanisch, Uwe-Karsten; Triebel, Jakob; Bollheimer, L Cornelius; Sieber, Cornel; Nau, Roland

    2015-01-07

    Meningoencephalitis caused by Escherichia coli is associated with high rates of mortality and risk of neurological sequelae in newborns and infants and in older or immunocompromised adults. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D. In vivo, we studied the effects of vitamin D3 on survival and the host's immune response in experimental bacterial meningoencephalitis in mice after intracerebral E. coli infection. To produce different systemic vitamin D3 concentrations, mice received a low, standard, or high dietary vitamin D3 supplementation. Bacterial titers in blood, spleen, and brain homogenates were determined. Leukocyte infiltration was assessed by histological scores, and tissue cytokine or chemokine concentrations were measured. Mice fed a diet with low vitamin D3 concentration died earlier than control animals after intracerebral infection. Vitamin D deficiency did not inhibit leukocyte recruitment into the subarachnoid space and did not lead to an increased density of bacteria in blood, spleen, or brain homogenates. The release of proinflammatory interleukin (IL)-6 was decreased and the release of anti-inflammatory IL-10 was increased in mice fed a diet with high vitamin D3 supplementation. Our observations suggest a detrimental role of vitamin D deficiency in bacterial central nervous system infections. Vitamin D may exert immune regulatory functions.

  13. Vitamin D and the skin: an ancient friend, revisited.

    Science.gov (United States)

    Reichrath, Jörg

    2007-07-01

    Most vertebrates need vitamin D to develop and maintain a healthy mineralized skeleton. However, 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D(3)], the biologically active vitamin D metabolite, exerts a multitude of important physiological effects independent from the regulation of calcium and bone metabolism. We know today that the skin has a unique role in the human body's vitamin D endocrine system. It is the only site of vitamin D photosynthesis, and has therefore a central role in obtaining a sufficient vitamin D status. Additionally, the skin has the capacity to synthesize the biologically active vitamin D metabolite 1,25(OH)(2)D(3), and represents an important target tissue for 1,25(OH)(2)D(3). In keratinocytes and other cell types, 1,25(OH)(2)D(3) regulates growth and differentiation. Consequently, vitamin D analogues have been i