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Sample records for 25oh vitamin d3

  1. Effect of 24,25-dihydroxyvitamin D3 on 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) metabolism in vitamin D-deficient rats infused with 1,25-(OH)2D3

    SciTech Connect

    Yamato, H.; Matsumoto, T.; Fukumoto, S.; Ikeda, K.; Ishizuka, S.; Ogata, E.

    1989-01-01

    Previous studies revealed that administration of 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) to calcium (Ca)-deficient rats causes a dose-dependent reduction in markedly elevated serum 1,25-(OH)2D3 level. Although the results suggested that the metabolism of 1,25-(OH)2D3 was accelerated by 24,25-(OH)2D3, those experiments could not define whether the enhanced metabolism of 1,25-(OH)2D3 played a role in the reduction in the serum 1,25-(OH)2D3 level. In the present study, in order to address this issue more specifically, serum 1,25-(OH)2D3 was maintained solely by exogenous administration through miniosmotic pumps of 1,25-(OH)2D3 into vitamin D-deficient rats. Thus, by measuring the serum 1,25-(OH)2D3 concentration, the effect of 24,25-(OH)2D3 on the MCR of 1,25-(OH)2D3 could be examined. Administration of 24,25-(OH)2D3 caused a dose-dependent enhancement in the MCR of 1,25-(OH)2D3, and 1 microgram/100 g rat.day 24,25-(OH)2D3, which elevated serum 24,25-(OH)2D3 to 8.6 +/- 1.3 ng/ml, significantly increased MCR and suppressed serum levels of 1,25-(OH)2D3. The effect of 24,25-(OH)2D3 on 1,25-(OH)2D3 metabolism developed with a rapid time course, and the recovery of iv injected (1 beta-3H)1,25-(OH)2D3 in blood was significantly reduced within 1 h. In addition, there was an increase in radioactivity in the water-soluble fraction of serum as well as in urine, suggesting that 1,25-(OH)2D3 is rapidly degraded to a water-soluble metabolite(s). Furthermore, the reduction in serum 1,25-(OH)2D3 was associated with a reduction in both serum and urinary Ca levels. Because the conversion of (3H)24,25-(OH)2D3 to (3H)1,24,25-(OH)2D3 or other metabolites was minimal in these rats, 24,25-(OH)2D3 appears to act without being converted into other metabolites. These results demonstrate that 24,25-(OH)2D3 rapidly stimulates the metabolism of 1,25-(OH)2D3 and reduces its serum level.

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

    PubMed Central

    Rogal, Karolina; Mankowska, Aneta

    2011-01-01

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

  3. Association of serum 25(OH) vitamin D3 concentration with severity of multiple sclerosis

    PubMed Central

    Shahbeigi, Saeed; Pakdaman, Hosein; Fereshtehnejad, Seyed-Mohammad; Nikravesh, Elham; Jalilzadeh, Roghie

    2012-01-01

    Background There is a known inverse association between solar radiation and the prevalence of multiple sclerosis (MS). Some studies have investigated the link between vitamin D and MS. The aim of this study was to investigate the possible association between serum 25(OH) vitamin D3 concentration and the severity of disease in Iranian patients with MS. Methods Patients with relapsing–remitting MS underwent neurological examination, including measurement of Expanded Disability Status Scale (EDSS) score, and were categorized by disease severity into mild (0 ≤ EDSS ≤3), moderate (3.5 ≤ EDSS ≤5.5) and severe (6 ≤ EDSS). Serum concentrations of 25(OH) vitamin D3, calcium, phosphorus, magnesium and parathyroid hormone were also measured. Results A total of 78 (73.1% female) patients with MS were evaluated. The mean (± standard deviation) of age was 33.9 ± 9.2 years. The mean (± standard error) serum concentrations of 25(OH) vitamin D3 were 36.6 ± 5.1 mg/dL, 50.1 ± 12.6 mg/dL and 19.8 ± 6.5 mg/dL in patients with mild, moderate and severe disease, respectively. There was a statistically significant inverse correlation between 25(OH) vitamin D3 concentration and EDSS score (P = 0.016, r= –0.273 by Spearman rank correlation test), which was observed in women only (P = 0.021, r = –0.305). Receiver operating characteristic curve analysis suggested that a serum 25(OH) vitamin D3 concentration cutoff of 16.5 mg/dL could differentiate patients with mild/moderate MS from severe disease with 74.6% accuracy. Conclusion Our findings further support the association between vitamin D and disease severity in MS. PMID:24250862

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

    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

  6. Vitamin D3 Effects on Lipids Differ in Statin and Non-Statin-Treated Humans: Superiority of Free 25-OH D Levels in Detecting Relationships

    PubMed Central

    Kane, Lynn; Moore, Kelly; Lütjohann, Dieter; Bikle, Daniel

    2013-01-01

    Context: Inverse associations between 25-OH vitamin D levels and cardiovascular morbidity and mortality have been reported. Objectives: Our goals were to 1) investigate effects of correcting inadequate D status on lipids, 2) determine whether free 25-OH D is better correlated with lipids than total 25-OH D. Design: A randomized, double-blind placebo-controlled trial was performed. Setting: Participants resided in the general community. Participants: Adults with inadequate D status were randomized to D3: 14 men, 12 women, age 60 ± 8 years (mean ± SD) or placebo: 12 men, 11 women: 59 ±12 years. Intervention: Responses to 12-week oral vitamin D3 titrated (1000–3000 IU/d) to achieve 25-OH D levels ≥25 ng/mL were compared to placebo. Main Outcome Measures: Measurements were 25-OH D (tandem mass spectometry), free 25-OH D (direct immunoassay), lipids (directly measured triglyceride, cholesterol, and subfractions; plant sterols and cholesterol synthesis precursors), and safety labs before and after 6 and 12 weeks D3 or placebo. Data were analyzed by repeated measures ANOVA and linear regression. Results: Vitamin D3 was titrated to 1000 IU/d in 15/26 (58%), to 2000 IU/d in 10, and 3000 IU/d in one patient. D3 had no effect on cholesterol or cholesterol subfractions except for trends for decreases in atorvastatin-treated patients (cholesterol, P = .08; low-density lipoprotein [LDL] cholesterol, P = .05). Decreased campesterol concentrations (P = .05) were seen with D3 but not placebo in statin-treated patients. Relationships between total 25-OH D and lipids were not detected, but inverse linear relationships were detected between free 25-OH D and triglycerides (P = .03 for all participants [n = 49], P = .03 in all statin-treated [n = 19], and P = .0009 in atorvastatin-treated [n = 11]), and between free 25-OH D and LDL cholesterol (P = .08 overall, P = .02 in all statin-treated, and P = .03 for atorvastatin-treated), and total cholesterol (P = .09 overall; P = .04

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

    PubMed

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

    2016-01-01

    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 < 0.05). Compared with that in control group, the expression of TNF-α, ET, eNOS, and CD106 was significantly upregulated in the T2DM group and the treatment group, while the expression of CD54 was increased only in the T2DM group (P < 0.05). Moreover, the levels of TNF-α, CD54, and CD106 in rats from the treatment group were lower than those in the T2DM group (P < 0.05). These data suggest that 1,25-(OH)2D3 may protect the macrovessels from injury in T2DM rats by inhibiting the expression of TNF-α, CD54, and CD106. PMID:27323139

  8. Ca2(+)-channel agonist BAY K8644 mimics 1,25(OH)2-vitamin D3 rapid enhancement of Ca2+ transport in chick perfused duodenum

    SciTech Connect

    de Boland, A.R.; Nemere, I.; Norman, A.W. )

    1990-01-15

    To further understand the molecular mechanism by which 1,25(OH)2-vitamin D3 (1,25(OH)2D3) rapidly stimulates intestinal calcium transport (termed transcaltachia), the effect of the calcium channel agonist BAY K8644 was studied in vascularly perfused duodenal loops from normal, vitamin D-replete chicks. BAY K8644, 2 mu M, was found to stimulate {sup 45}Ca{sup 2+} transport from the lumen to the vascular effluent to the same extent as physiological levels of 1,25(OH)2D3. The sterol and the Ca{sup 2+} channel agonist both increased {sup 45}Ca{sup 2+} transport 70% above control values within 2 min and 200% after 30 min of vascular perfusion. The effect of the Ca{sup 2+} channel agonist was dose dependent. Also, 1,25(OH)2D3-enhanced transcaltachia was abolished by the calcium channel blocker nifedipine. Collectively, these results suggest the involvement of 1,25(OH)2D3 in the activation of basal lateral membrane Ca{sup 2+} channels as an early effect in the transcaltachic response.

  9. Effects of Oxcarbazepine and Levetiracetam on Calcium, Ionized Calcium, and 25-OH Vitamin-D3 Levels in Patients with Epilepsy

    PubMed Central

    Aksoy, Duygu; Güveli, Betül Tekin; Ak, Pelin Doğan; Sarı, Hüseyin; Ataklı, Dilek; Arpacı, Baki

    2016-01-01

    Objective The primary objective of the present study was to further elucidate the effects of oxcarbazepine (OXC) and levetiracetam (LEV) monotherapies on the bone health status of patients with epilepsy. Methods This study included 48 patients who attended our epilepsy outpatient clinic, had a diagnosis of epilepsy, and were undergoing either OXC or LEV monotherapy and 42 healthy control subjects. The demographic and clinical features of the patients, including gender, age, onset of disease, daily drug dosage, and duration of disease, were noted. Additionally, the calcium, ionized calcium, and 25-OH vitamin-D3 levels of the participants were prospectively evaluated. Results The 25-OH vitamin-D3, calcium, and ionized calcium levels of the patients taking OXC were significantly lower than those of the control group. These levels did not significantly differ between the patients taking LEV and the control group, but there was a significant negative relationship between daily drug dose and ionized calcium levels in the LEV patients. Conclusion In the present study, anti-epileptic drugs altered the calcium, ionized calcium, and 25-OH vitamin-D3 levels of epilepsy patients and resulted in bone loss, abnormal mineralization, and fractures. These findings suggest that the calcium, ionized calcium, and 25-OH vitamin-D3 levels of patients with epilepsy should be regularly assessed. PMID:26792043

  10. 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

    PubMed Central

    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

  11. Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60.

    PubMed

    Peacock, M; Liu, G; Carey, M; McClintock, R; Ambrosius, W; Hui, S; Johnston, C C

    2000-09-01

    Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures. A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites, bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a randomized, double-blind, placebo-controlled trial. Bone mineral density (BMD) was measured by dual x-ray absorptiometry and bone structure by radiographs. Calcium biochemistry and bone turnover markers were measured in blood and urine. The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr. Baseline median calcium intake was 546 mg/day, and median serum 25OH vitamin D3 was 59 nmol/L. On placebo, loss of BMD at total hip was 2% and femoral medulla expansion was 3% over 4 yr. Calcium reduced bone loss, secondary hyperparathyroidism, and bone turnover. 25OH vitamin D3 was intermediate between placebo and calcium. Fracture rates and drop-out rates were similar among groups, and there were no serious adverse events with either supplement. A calcium supplement of 750 mg/day prevents loss of BMD, reduces femoral medullary expansion, secondary hyperparathyroidism, and high bone turnover. A supplement of 15 microg/day 25OH vitamin D3 is less effective, and because its effects are seen only at low calcium intakes, suggests that its beneficial effect is to reverse calcium insufficiency. PMID:10999778

  12. Nasal Levels of Antimicrobial Peptides in Allergic Asthma Patients and Healthy Controls: Differences and Effect of a Short 1,25(OH)2 Vitamin D3 Treatment

    PubMed Central

    Thijs, Willemien; Janssen, Kirsten; van Schadewijk, Annemarie M.; Papapoulos, Socrates E.; le Cessie, Saskia; Middeldorp, Saskia; Melissant, Christian F.; Rabe, Klaus F.; Hiemstra, Pieter S.

    2015-01-01

    Background 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(OH)2D3) affects these antimicrobial peptide levels. Methods 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(OH)2D3 on antimicrobial peptides in nasal secretions was assessed in a placebo-controlled cross-over clinical study. Results 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(OH)2D3 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(OH)2D3. Conclusion 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. PMID:26545199

  13. Effects of 1,25(OH)2 D3 and 25(OH)D3 on C2C12 Myoblast Proliferation, Differentiation, and Myotube Hypertrophy.

    PubMed

    van der Meijden, K; Bravenboer, N; Dirks, N F; Heijboer, A C; den Heijer, M; de Wit, G M J; Offringa, C; Lips, P; Jaspers, R T

    2016-11-01

    An adequate vitamin D status is essential to optimize muscle strength. However, whether vitamin D directly reduces muscle fiber atrophy or stimulates muscle fiber hypertrophy remains subject of debate. A mechanism that may affect the role of vitamin D in the regulation of muscle fiber size is the local conversion of 25(OH)D to 1,25(OH)2 D by 1α-hydroxylase. Therefore, we investigated in a murine C2C12 myoblast culture whether both 1,25(OH)2 D3 and 25(OH)D3 affect myoblast proliferation, differentiation, and myotube size and whether these cells are able to metabolize 25(OH)D3 and 1,25(OH)2 D3 . We show that myoblasts not only responded to 1,25(OH)2 D3 , but also to the precursor 25(OH)D3 by increasing their VDR mRNA expression and reducing their proliferation. In differentiating myoblasts and myotubes 1,25(OH)2 D3 as well as 25(OH)D3 stimulated VDR mRNA expression and in myotubes 1,25(OH)2 D3 also stimulated MHC mRNA expression. However, this occurred without notable effects on myotube size. Moreover, no effects on the Akt/mTOR signaling pathway as well as MyoD and myogenin mRNA levels were observed. Interestingly, both myoblasts and myotubes expressed CYP27B1 and CYP24 mRNA which are required for vitamin D3 metabolism. Although 1α-hydroxylase activity could not be shown in myotubes, after treatment with 1,25(OH)2 D3 or 25(OH)D3 myotubes showed strongly elevated CYP24 mRNA levels compared to untreated cells. Moreover, myotubes were able to convert 25(OH)D3 to 24R,25(OH)2 D3 which may play a role in myoblast proliferation and differentiation. These data suggest that skeletal muscle is not only a direct target for vitamin D3 metabolites, but is also able to metabolize 25(OH)D3 and 1,25(OH)2 D3 . J. Cell. Physiol. 231: 2517-2528, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  14. 1α,25(OH)2 Vitamin D3 Modulates Avian T Lymphocyte Functions without Inducing CTL Unresponsiveness

    PubMed Central

    Boodhoo, Nitish; Sharif, Shayan; Behboudi, Shahriar

    2016-01-01

    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. PMID:26910045

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  16. 25(OH)D Is Effective to Repress Human Cholangiocarcinoma Cell Growth through the Conversion of 25(OH)D to 1α,25(OH)2D3

    PubMed Central

    Chiang, Kun-Chun; Yeh, Chun-Nan; Huang, Cheng-Cheng; Yeh, Ta-Sen; S. Pang, Jong-Hwei; Hsu, Jun-Te; Chen, Li-Wei; Kuo, Sheng-Fong; Kittaka, Atsushi; Chen, Tai C.; Juang, Horng-Heng

    2016-01-01

    Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1α,25(OH)2D3, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1α,25(OH)2D3, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1α,25(OH)2D3 has been found in some cancer cells with CYP27B1 expression. In this study, CYP27B1 expression was demonstrated in CCA cells and human CCA specimens. 25(OH)D effectively represses SNU308 cells growth, which was strengthened or attenuated as CYP27B1 overexpression or knockdown. Lipocalcin-2 (LCN2) was also found to be repressed by 25(OH)D. After treatment with 800 ng/mL 25(OH)D, the intracellular 1α,25(OH)2D3 concentration was higher in SNU308 cells with CYP27B1 overexpression than wild type SNU308 cells. In a xenograft animal experiment, 25(OH)D, at a dose of 6 μg/kg or 20 μg/kg, significantly inhibited SNU308 cells’ growth without inducing obvious side effects. Collectively, our results indicated that SNU308 cells were able to convert 25(OH)D to 1α,25(OH)2D3 and 25(OH)D CYP27B1 gene therapy could be deemed as a promising therapeutic direction for CCA. PMID:27529229

  17. 1,25(OH)2D3 increases membrane associated protein kinase C in MDBK cells.

    PubMed

    Simboli-Campbell, M; Franks, D J; Welsh, J

    1992-01-01

    To determine whether 1,25-dihydroxycholecalciferol [1,25(OH)2D3] affects protein kinase C (PKC) activity in kidney, as has been demonstrated in HL-60 cells we measured 1,25(OH)2D3 binding, PKC activity and PKC immunoreactivity in Madin Darby bovine kidney (MDBK) cells, a normal renal epithelial cell line derived from bovine kidney. Our data demonstrate that MDBK cells exhibit specific high affinity binding for 1,25(OH)2D3, indicating the presence of the vitamin D receptor (VDR). Treatment of MDBK cells with 1,25(OH)2D3 for 24 h increased membrane PKC activity and immunoreactivity. The effect of 1,25(OH)2D3 was dose-dependent, with a peak effect observed at 10(-7)M 1,25(OH)2D3. The 1,25(OH)2D3 induced increase in membrane PKC was paralleled by a comparable decrease in cytosolic PKC activity and amount. Although time course studies were consistent with a VDR mediated effect of 1,25(OH)2D3 on PKC protein synthesis, total PKC activity was not increased by 1,25(OH)2D3, suggesting an effect on PKC translocation or localization. These results suggest that 1,25(OH)2D3 modulates PKC mediated events in kidney, a classic target for this steroid hormone.

  18. Activation of RAF-1 through Ras and protein kinase Calpha mediates 1alpha,25(OH)2-vitamin D3 regulation of the mitogen-activated protein kinase pathway in muscle cells.

    PubMed

    Buitrago, Claudia Graciela; Pardo, Veronica González; de Boland, Ana R; Boland, Ricardo

    2003-01-24

    We have previously shown that stimulation of proliferation of avian embryonic muscle cells (myoblasts) by 1alpha,25(OH)(2)-vitamin D(3) (1alpha,25(OH)(2)D(3)) is mediated by activation of the mitogen-activated protein kinase (MAPK; ERK1/2). To understand how 1alpha,25(OH)(2)D(3) up-regulates the MAPK cascade, we have investigated whether the hormone acts upstream through stimulation of Raf-1 and the signaling mechanism by which this effect might take place. Treatment of chick myoblasts with 1alpha,25(OH)(2)D(3) (1 nm) caused a fast increase of Raf-1 serine phosphorylation (1- and 3-fold over basal at 1 and 2 min, respectively), indicating activation of Raf-1 by the hormone. These effects were abolished by preincubation of cells with a specific Ras inhibitor peptide that involves Ras in 1alpha,25(OH)(2)D(3) stimulation of Raf-1. 1alpha,25(OH)(2)D(3) rapidly induced tyrosine de-phosphorylation of Ras-GTPase-activating protein, suggesting that inhibition of Ras-GTP hydrolysis is part of the mechanism by which 1alpha,25(OH)(2)D(3) activates Ras in myoblasts. The protein kinase C (PKC) inhibitors calphostin C, bisindolylmaleimide I, and Ro 318220 blocked 1alpha,25(OH)(2)D(3)-induced Raf-1 serine phosphorylation, revealing that hormone stimulation of Raf-1 also involves PKC. In addition, transfection of muscle cells with an antisense oligodeoxynucleotide against PKCalpha mRNA suppressed serine phosphorylation by 1alpha,25(OH)(2)D(3). The increase in MAPK activity and tyrosine phosphorylation caused by 1alpha,25(OH)(2)D(3) could be abolished by Ras inhibitor peptide, compound PD 98059, which prevents the activation of MEK by Raf-1, or incubation of cell lysates before 1alpha,25(OH)(2)D(3) exposure with an anti-Raf-1 antibody. In conclusion, these results demonstrate for the first time in a 1alpha,25(OH)(2)D(3) target cell that activation of Raf-1 via Ras and PKCalpha-dependent serine phosphorylation plays a central role in hormone stimulation of the MAPK-signaling pathway

  19. Caveolae and caveolin-1 are implicated in 1alpha,25(OH)2-vitamin D3-dependent modulation of Src, MAPK cascades and VDR localization in skeletal muscle cells.

    PubMed

    Buitrago, Claudia; Boland, Ricardo

    2010-07-01

    We previously reported that 1alpha,25(OH)2D3 induces non-transcriptional rapid responses through activation of MAPKs in C2C12 skeletal muscle cells. However, there is little information on the molecular mechanism underlying the initiation of 1alpha,25(OH)2D3 signaling through this pathway. Plasma membrane components have been involved in some non-genomic effects. In this work, we investigated the role of caveolae and caveolin-1 (cav-1) in 1alpha,25(OH)2D3-stimulation of c-Src and MAPKs. When proliferating cells were pretreated with methyl beta cyclodextrin (MbetaCD), a caveolae disrupting agent, under conditions in which cell morphology is not affected and no signs of apoptosis are observed, 1alpha,25(OH)2D3-dependent activation of ERK1/2, p38 MAPK and c-Src was suppressed. Similar results were obtained by siRNA technology whereby silencing of cav-1 expression abolished activation of c-Src and MAPKs induced by the hormone. By confocal immunocytochemistry it was observed that cav-1 colocalizes with c-Src in the periplasma membrane zone at basal conditions. Hormone treatment disrupted the colocalization of these proteins and redistributed them into cytoplasm and nucleus. Co-immunoprecipitation assays corroborated these observations. Changes in VDR localization after 1alpha,25(OH)2D3 exposure were also investigated. Confocal microscopy images showed that the hormone induces VDR translocation to the plasma membrane, and this effect is abolished by MbetaCD. Altogether, these data suggest that caveolae is involved upstream in c-Src-MAPKs activation by 1alpha,25(OH)2D3 and that VDR and cav-1 participate in the rapid signaling elicited by the hormone.

  20. Quantitation of 25-OH-Vitamin-D₂ and 25-OH-Vitamin-D₃ in Urine Using LC-MS/MS.

    PubMed

    Carlow, Dean C; Schofield, Ryan C; Denburg, Michelle

    2016-01-01

    Patients with significant proteinuria represent a unique population with respect to vitamin D status due to the urinary losses of vitamin D-binding protein (DBP) to which >99 % of circulating 25-hydroxy vitamin D (25(OH)D) is bound. Low serum concentrations of 25(OH)D have been found in children and adults with nephrotic syndrome (NS). However, previously described assays developed to quantify the magnitude of urinary loss are technically challenging. This chapter describes a simple and sensitive method to quantify 25(OH)D2 and 25(OH)D3 in urine specimens in a single analytical LC-MS/MS analysis. This assay is more sensitive than previously described radioimmunoassays and offers the ability to quantitate both forms of 25-hydroxy vitamin D. The assay involves no chemical derivitization, has a linear measurement range of 20-1500 pg/mL and displays imprecision (CVs) below 7 % at various concentrations across the analytical measurement range.

  1. Assessing novel prognostic serum biomarkers in advanced pancreatic cancer: the role of CYFRA 21-1, serum amyloid A, haptoglobin, and 25-OH vitamin D3.

    PubMed

    Haas, Michael; Kern, Christoph; Kruger, Stephan; Michl, Marlies; Modest, Dominik P; Giessen, Clemens; Schulz, Christoph; von Einem, Jobst C; Ormanns, Steffen; Laubender, Rüdiger P; Holdenrieder, Stefan; Heinemann, Volker; Boeck, Stefan

    2015-04-01

    The present prospective single-center study investigated the prognostic role of novel serum biomarkers in advanced pancreatic cancer (PC). Patients (pts) with locally advanced or metastatic PC treated with first-line palliative chemotherapy were included. Among others, the serum markers CYFRA 21-1, haptoglobin, serum-amyloid A (SAA), and 25-OH vitamin D3 were determined at baseline and categorized by pre-defined cut-offs [median values (MV), upper limits of normal (ULN), lower limits of normal (LLN), or the natural logarithm (ln)] and correlated with overall survival (OS). Among the 59 pts included, pre-treatment CYFRA 21-1 levels showed a strong correlation with OS independent of the applied cut-off (MV 4.9 ng/ml-14.2 vs. 4.2 months, HR 0.18, p = 0.001; ULN 3.3 ng/ml-14.2 vs. 4.4 months, HR 0.28, p = 0.003; [ln] CYFRA 21-1-HR 0.77, p = 0.013). Lower values of haptoglobin were additionally associated with an improvement in OS (categorized by LLN of 2.05 g/l-10.4 vs. 5.5 months, HR 0.46, p = 0.023; [ln] haptoglobin-HR 0.51, p = 0.036). Pts with baseline SAA values below the MV of 22 mg/l also had a prolonged OS (10.4 vs. 5.0 months, HR 0.47, p = 0.036). For 25-OH vitamin D3 levels, no significant correlation with OS was found. In multivariate analyses, pre-treatment CYFRA 21-1 levels (categorized by MV-HR 0.15, p = 0.032) as well as [ln] haptoglobin (HR 0.30, p = 0.006) retained their independent prognostic significance for OS. CYFRA 21-1, haptoglobin, and SAA might provide useful prognostic information in advanced PC. An external multicenter validation of these results is necessary. PMID:25472579

  2. ERK 5/MAPK PATHWAY HAS A MAJOR ROLE IN 1α,25-(OH)2 VITAMIN D3-INDUCED TERMINAL DIFFERENTIATION OF MYELOID LEUKEMIA CELLS

    PubMed Central

    Wang, Xuening; Pesakhov, Stella; Weng, Ashley; Kafka, Michael; Gocek, Elzbieta; Nguyen, Mai; Harrison, Jonathan S.; Danilenko, Michael; Studzinski, George P.

    2013-01-01

    Vitamin D derivatives, including its physiological form 1α,25(OH)2 vitamin D3 (1,25D), have anti-tumor actions demonstrated in cell culture and confirmatory epidemiological associations are frequently reported. However, their promise for use in the cancer clinic is still incompletely fulfilled, suggesting that a better understanding of the molecular events initiated by these compounds is needed for therapeutic advances. While ERK1/2 has been intensely investigated and is known to transmit signals for cell survival, growth, and differentiation, the role of other MAPK pathways has been studied sporadically. Therefore, we utilized acute myeloid leukemia (AML) cells in culture (HL60 and U937), to determine if ERK5 has a role in 1,25D-induced terminal differentiation which is distinct from the previously shown involvement of ERK1/2. We previously found that inhibition of kinase activity of ERK5 by specific pharmacological inhibitors BIX02189 or XMD8-92 results in higher expression of general myeloid marker CD11b, but a lower expression of the monocytic marker CD14. In contrast, the inhibition of the ERK1/2 pathway by PD98059 or U0126 reduced the expression of all differentiation markers studied. We report here for the first time that the differentiation changes induced by ERK5 inhibitors are accompanied by the inhibition of cell proliferation, and this occurs in the both G1 and G2 phases of the cell cycle. Of note, inhibition of ERK5 auto-phosphorylation by XMD8-92 results in a particularly robust cell cycle arrest in G2 phase in AML cells. This study provides a link between the 1,25D-elevated ERK5 pathway and changes in the cell cycle phase transitions in AML cells. Thus, combinations of vitamin D derivatives and ERK5 inhibitors may be more successful in cancer clinics than 1,25D or analogs alone. PMID:24514755

  3. Interactions between 1alpha,25(OH)2D3 and residues in the ligand-binding pocket of the vitamin D receptor: a correlated fragment molecular orbital study.

    PubMed

    Yamagishi, Kenji; Tokiwa, Hiroaki; Makishima, Makoto; Yamada, Sachiko

    2010-07-01

    To provide physicochemical insight into the role of each residue in the ligand-binding pocket (LBP) of the vitamin D receptor (VDR), we evaluated the energies of the interactions between the LBP residues and 1alpha,25(OH)2D3 by using an ab initio fragment molecular orbital (FMO) method at the Møller-Plesset second-order perturbation (MP2) level. This FMO-MP2 method can be used to correctly evaluate both electrostatic and van der Waals dispersion interactions, and it affords these interaction energies separately. We deduced the nature of each interaction and determined the importance of all the LBP residues involved in ligand recognition by the VDR. We previously reported the results of alanine-scanning mutational analysis (ASMA) of all 34 non-alanine residues lining the LBP of the human VDR. The theoretical results in combination with the ASMA results enabled us to assign the role of each LBP residue. We concluded that electrostatic interactions are the major determinant of the ligand-binding activity and ligand recognition specificity and that van der Waals interactions are important for protein folding and, in turn, for cofactor binding.

  4. Vitamin D deficiency in guinea pigs: exacerbation of bone phenotype during pregnancy and disturbed fetal mineralization, with recovery by 1,25(OH)2D3 infusion or dietary calcium-phosphate supplementation.

    PubMed

    Rummens, K; van Bree, R; Van Herck, E; Zaman, Z; Bouillon, R; Van Assche, F A; Verhaeghe, J

    2002-10-01

    Vitamin D (D) deficiency during human pregnancy appears to disturb fetal growth and mineralization, but fetal development is normal in D-deficient rats and vitamin D receptor gene-ablated mice. We used the guinea pig model to investigate maternal and fetal effects of D deficiency. Pregnant (Pr) and nonpregnant (NPr) animals were fed a D-replete (+D) or D-deficient diet (-D) for 8 weeks. We further studied whether the effects of a -D diet are reversed by continuous 1,25(OH)2D3 infusion (-D+1,25) and/or by a lactose-, Ca- and P-enriched D-deficient diet (-D+Ca/P). Bone analyses included histomorphometry of the proximal tibiae, dual-energy X-ray absorptiometry (DXA), and quantitative computed tomography (QCT) of the femora. Depletion of 25(OH)D3 and 1,25(OH)2D3 levels and the D-deficiency syndrome were more severe in pregnant animals. Indeed, Pr/-D but not NPr/-D guinea pigs were hypophosphatemic, and showed robust increases in growth plate width and osteoid surface and thickness; in addition, bone mineral density on DXA was lower in Pr/-D animals only, which was exclusively in cortical bone on QCT. Bone phenotype was partly normalized in Pr/-D+1,25 and Pr/-D+Ca/P animals. Compared with +D fetuses, -D fetuses had very low or undetectable 25(OH)D3 and 1,25(OH)2D3, were hypercalcemic and hypophosphatemic, and had lower osteocalcin levels. In addition, body weight and total body bone mineral content were 10-15% lower; histomorphometry showed hypertrophic chondrocyte zone expansion and hyperosteoidosis. 1,25(OH)2D3 levels were restored in -D+1,25 fetuses, and the phenotype was partially corrected. Similarly, the fetal +D phenotype was rescued in large part in -D+Ca/P fetuses, despite undetectable circulating 25(OH)D3 and 1,25(OH)2D3. We conclude that pregnancy markedly exacerbates D deficiency, and that augmenting Ca and P intake overrides the deleterious effects of D deficiency on fetal development.

  5. Modifying broiler diets with phytase and vitamin D metabolite (25-OH D(3)): impact on phosphorus in litter, amended soils, and runoff.

    PubMed

    McGrath, Joshua M; Sims, J Thomas; Maguire, Rory O; Saylor, William W; Angel, Roselina

    2010-01-01

    Adding phytase and 25- hydroxycholecalciferol (25-OH D(3)) to broiler diets has been shown effective at reducing total P concentrations in broiler litter. This study was conducted to determine the impact of field application of broiler litter from modified diets on P solubility in litter-amended soils and P losses in runoff. Five broiler diets and their resulting litters were evaluated: a high P diet, a low P diet, each of those basal diets with phytase added, and a low P diet with phytase and 25-OH D(3) added. A field study was initiated at two sites with each of the five broiler litters and a commercial P fertilizer (triple superphosphate [TSP]) applied at the same total P rate (150 kg P ha(-1)) and a control where no P was applied. Soil P was monitored over time at two depths (0-5 cm and 0-15 cm) soils were collected in the spring and fall to perform rainfall simulation studies. Broiler litter or TSP application increased soil water-soluble P and Mehlich 3-P concentrations relative to the control, however there were no consistent differences detected between litter treatments. Results from the rainfall simulation experiments indicate that diet modification with phytase or 25-OH D(3) does not increase the potential for P losses in runoff from amended soils relative to traditional diets. Moreover, broiler diet modification to reduce excreted P could be a potentially effective method for reducing watershed scale P surpluses in areas of intensive broiler production, without raising concerns over soluble P losses from litter-amended soils. PMID:20048320

  6. Vector-averaged gravity-induced changes in cell signaling and vitamin D receptor activity in MG-63 cells are reversed by a 1,25-(OH)2D3 analog, EB1089

    NASA Technical Reports Server (NTRS)

    Narayanan, R.; Smith, C. L.; Weigel, N. L.

    2002-01-01

    Skeletal unloading in an animal hindlimb suspension model and microgravity experienced by astronauts or as a result of prolonged bed rest causes site-specific losses in bone mineral density of 1%-2% per month. This is accompanied by reductions in circulating levels of 1,25-(OH)(2)D(3), the active metabolite of vitamin D. 1,25-(OH)(2)D(3), the ligand for the vitamin D receptor (VDR), is important for calcium absorption and plays a role in differentiation of osteoblasts and osteoclasts. To examine the responses of cells to activators of the VDR in a simulated microgravity environment, we used slow-turning lateral vessels (STLVs) in a rotating cell culture system. We found that, similar to cells grown in microgravity, MG-63 cells grown in the STLVs produce less osteocalcin, alkaline phosphatase, and collagen Ialpha1 mRNA and are less responsive to 1,25-(OH)(2)D(3). In addition, expression of VDR was reduced. Moreover, growth in the STLV caused activation of the stress-activated protein kinase pathway (SAPK), a kinase that inhibits VDR activity. In contrast, the 1,25-(OH)(2)D(3) analog, EB1089, was able to compensate for some of the STLV-associated responses by reducing SAPK activity, elevating VDR levels, and increasing expression of osteocalcin and alkaline phosphatase. These studies suggest that, not only does simulated microgravity reduce differentiation of MG-63 cells, but the activity of the VDR, an important regulator of bone metabolism, is reduced. Use of potent, less calcemic analogs of 1,25-(OH)(2)D(3) may aid in overcoming this defect. Copyright 2002 Elsevier Science Inc.

  7. 1,25(OH)2D3 dependent overt hyperactivity phenotype in klotho-hypomorphic mice

    PubMed Central

    Leibrock, Christina B.; Voelkl, Jakob; Kuro-o, Makoto; Lang, Florian; Lang, Undine E

    2016-01-01

    Klotho, a protein mainly expressed in kidney and cerebral choroid plexus, is a powerful regulator of 1,25(OH)2D3 formation. Klotho-deficient mice (kl/kl) suffer from excessive plasma 1,25(OH)2D3-, Ca2+- and phosphate-concentrations, leading to severe soft tissue calcification and accelerated aging. NH4Cl treatment prevents tissue calcification and premature ageing without affecting 1,25(OH)2D3-formation. The present study explored the impact of excessive 1,25(OH)2D3 formation in NH4Cl-treated kl/kl-mice on behavior. To this end kl/kl-mice and wild-type mice were treated with NH4Cl and either control diet or vitamin D deficient diet (LVD). As a result, plasma 1,25(OH)2D3-, Ca2+- and phosphate-concentrations were significantly higher in untreated and in NH4Cl-treated kl/kl-mice than in wild-type mice, a difference abrogated by LVD. In each, open field, dark-light box, and O-maze NH4Cl-treated kl/kl-mice showed significantly higher exploratory behavior than untreated wild-type mice, a difference abrogated by LVD. The time of floating in the forced swimming test was significantly shorter in NH4Cl treated kl/kl-mice compared to untreated wild-type mice and to kl/kl-mice on LVD. In wild-type animals, NH4Cl treatment did not significantly alter 1,25(OH)2D3, calcium and phosphate concentrations or exploratory behavior. In conclusion, the excessive 1,25(OH)2D3 formation in klotho-hypomorphic mice has a profound effect on murine behavior. PMID:27109615

  8. 1α,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells

    PubMed Central

    Ma, Yingyu; Hu, Qiang; Luo, Wei; Pratt, Rachel N.; Glenn, Sean T.; Liu, Song; Trump, Donald L.; Johnson, Candace S.

    2014-01-01

    Bladder cancer is the fourth most commonly diagnosed cancer in men and eighth leading cause of cancer-related death in the US. Epidemiological and experimental studies strongly suggest a role for 1α,25(OH)2D3 in cancer prevention and treatment. The antitumor activities of 1α,25(OH)2D3 are mediated by the induction of cell cycle arrest, apoptosis, differentiation and the inhibition of angiogenesis and metastasis. MiRNAs play important regulatory roles in cancer development and progression. However, the role of 1α,25(OH)2D3 in the regulation of miRNA expression and the potential impact in bladder cancer has not been investigated. Therefore, we studied 1α,25(OH)2D3-regulated miRNA expression profiles in human bladder cancer cell line 253J and the highly tumorigenic and metastatic derivative line 253J-BV by miRNA qPCR panels. 253 J and 253J-BV cells express endogenous vitamin D receptor (VDR) which can be further induced by 1α,25(OH)2D3. VDR target gene 24-hydroxylase was induced by 1α,25(OH)2D3 in both cell lines, indicating functional 1α,25(OH)2D3 signaling. The miRNA qPCR panel assay results showed that 253J and 253J-BV cells have distinct miRNA expression profiles. Further, 1α,25(OH)2D3 differentially regulated miRNA expression profiles in 253J and 253 J-BV cells in a dynamic manner. Pathway analysis of the miRNA target genes revealed distinct patterns of contribution to the molecular functions and biological processes in the two cell lines. In conclusion, 1α,25(OH)2D3 differentially regulates the expression of miRNAs, which may contribute to distinct biological functions, in human bladder 253J and 253J-BV cells. PMID:25263658

  9. 1,25 (OH)2D3 treatment alters the granulomatous response in M. tuberculosis infected mice

    PubMed Central

    Bhatt, Kamlesh; Rafi, Wasiulla; Shah, Neel; Christakos, Sylvia; Salgame, Padmini

    2016-01-01

    Induction of cathelicidin-mediated antimicrobial pathway against intracellular M. tuberculosis by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, has been documented in vitro. However, in in vivo studies related to inflammatory disorders, 1,25(OH)2D3 has been demonstrated to induce an anti-inflammatory response. We therefore examined whether in the murine model of tuberculosis, the anti-inflammatory effects of 1,25(OH)2D3 would affect the outcome of M. tuberculosis infection. We show here that administration of 1,25(OH)2D3 to M. tuberculosis infected mice led to a change in lung granuloma architecture, characterized by a marked decrease in B cell lymphocytic aggregates. Consistent with the altered granulomas, 1,25(OH)2D3-treated mice also exhibited significantly higher bacterial burden in the lungs compared to the control group. These findings highlight the need to further investigate the effect of vitamin D on host immunity to M. tuberculosis in the context of the granulomatous response. PMID:27698450

  10. Effect of 1,25(OH)2 vitamin D3 and ionized Ca/sup 2 +/ on /sup 45/Ca uptake by primary cultures of aortic myocytes of spontaneously hypertensive and Wistar Kyoto normotensive rats

    SciTech Connect

    Bukoski, R.D.; Xue, H.; McCarron, D.A.

    1987-08-14

    The effect of several regulators of whole animal Ca/sup 2 +/ homeostasis on /sup 45/Ca uptake by primary cultures of aortic myocytes isolated from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats was examined. Exposure of confluent cells to 1.0, 1.25 or 1.50 mM ionized Ca/sup 2 +/ in serum-free medium for seven days resulted in increased /sup 45/Ca uptake at the higher concentrations of Ca/sup 2 +/ in cells of the SHR but not the WKY. 1,25 (OH)2 vitamin D3 (1 ng/ml) for 7 days caused enhanced influx in cells from both the SHR and WKY while parathyroid hormone (1-34) (1 ng/ml) was without effect. The data indicate that humoral factors that serve to regulate whole animal Ca/sup 2 +/ homeostasis may also play a role in the regulation of Ca/sup 2 +/ metabolism of the vascular smooth muscle cell.

  11. 1α,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells.

    PubMed

    Ma, Yingyu; Hu, Qiang; Luo, Wei; Pratt, Rachel N; Glenn, Sean T; Liu, Song; Trump, Donald L; Johnson, Candace S

    2015-04-01

    Bladder cancer is the fourth most commonly diagnosed cancer in men and eighth leading cause of cancer-related death in the US. Epidemiological and experimental studies strongly suggest a role for 1α,25(OH)2D3 in cancer prevention and treatment. The antitumor activities of 1α,25(OH)2D3 are mediated by the induction of cell cycle arrest, apoptosis, differentiation and the inhibition of angiogenesis and metastasis. miRNAs play important regulatory roles in cancer development and progression. However, the role of 1α,25(OH)2D3 in the regulation of miRNA expression and the potential impact in bladder cancer has not been investigated. Therefore, we studied 1α,25(OH)2D3-regulated miRNA expression profiles in human bladder cancer cell line 253J and the highly tumorigenic and metastatic derivative line 253J-BV by miRNA qPCR panels. 253J and 253J-BV cells express endogenous vitamin D receptor (VDR), which can be further induced by 1α,25(OH)2D3. VDR target gene 24-hydroxylase was induced by 1α,25(OH)2D3 in both cell lines, indicating functional 1α,25(OH)2D3 signaling. The miRNA qPCR panel assay results showed that 253J and 253J-BV cells have distinct miRNA expression profiles. Further, 1α,25(OH)2D3 differentially regulated miRNA expression profiles in 253J and 253J-BV cells in a dynamic manner. Pathway analysis of the miRNA target genes revealed distinct patterns of contribution to the molecular functions and biological processes in the two cell lines. In conclusion, 1α,25(OH)2D3 differentially regulates the expression of miRNAs, which may contribute to distinct biological functions, in human bladder 253J and 253J-BV cells. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. PMID:25263658

  12. 1α,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells.

    PubMed

    Ma, Yingyu; Hu, Qiang; Luo, Wei; Pratt, Rachel N; Glenn, Sean T; Liu, Song; Trump, Donald L; Johnson, Candace S

    2015-04-01

    Bladder cancer is the fourth most commonly diagnosed cancer in men and eighth leading cause of cancer-related death in the US. Epidemiological and experimental studies strongly suggest a role for 1α,25(OH)2D3 in cancer prevention and treatment. The antitumor activities of 1α,25(OH)2D3 are mediated by the induction of cell cycle arrest, apoptosis, differentiation and the inhibition of angiogenesis and metastasis. miRNAs play important regulatory roles in cancer development and progression. However, the role of 1α,25(OH)2D3 in the regulation of miRNA expression and the potential impact in bladder cancer has not been investigated. Therefore, we studied 1α,25(OH)2D3-regulated miRNA expression profiles in human bladder cancer cell line 253J and the highly tumorigenic and metastatic derivative line 253J-BV by miRNA qPCR panels. 253J and 253J-BV cells express endogenous vitamin D receptor (VDR), which can be further induced by 1α,25(OH)2D3. VDR target gene 24-hydroxylase was induced by 1α,25(OH)2D3 in both cell lines, indicating functional 1α,25(OH)2D3 signaling. The miRNA qPCR panel assay results showed that 253J and 253J-BV cells have distinct miRNA expression profiles. Further, 1α,25(OH)2D3 differentially regulated miRNA expression profiles in 253J and 253J-BV cells in a dynamic manner. Pathway analysis of the miRNA target genes revealed distinct patterns of contribution to the molecular functions and biological processes in the two cell lines. In conclusion, 1α,25(OH)2D3 differentially regulates the expression of miRNAs, which may contribute to distinct biological functions, in human bladder 253J and 253J-BV cells. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

  13. Vitamin D3 metabolism in dogs.

    PubMed

    Hazewinkel, H A W; Tryfonidou, M A

    2002-11-29

    Plasma concentrations of the main vitamin D(3) metabolites (i.e., 25(OH)D(3), 1,25(OH)(2)D(3), and 24,25(OH)(2)D(3)) were measured in 14 weeks old large- and small-breed dogs (adult body weight 60 kg vs. 6 kg), raised under the same conditions. Levels of 25(OH)D(3) (approx. 22 microg/l) and 1,25(OH)(2)D(3) (approx. 40 ng/l) were similar in both groups, whereas plasma 24,25(OH)(2)D(3) concentrations were lower in large-breed dogs (7 microg/l vs. 70 microg/l, large- vs. small-breed dogs, respectively). The lower plasma 24,25(OH)(2)D(3) concentrations could be explained by the higher plasma GH and IGF-I concentrations in the large- vs. small-breed dogs, and these hormones are known to suppress 24-hydroxylation. Plasma 24,25(OH)(2)D(3) concentrations increased during Ca supplementation in small-breed but not in large-breed dogs (100 microg/l vs. 7 microg/l, respectively). Hypophosphatemia induced by a high dietary Ca content was only seen together with increased plasma 1,25(OH)(2)D(3) concentrations in euparathyroid dogs and not in hypoparathyroid dogs. Hyperparathyroidism due to Ca deficiency was accompanied by increased plasma 1,25(OH)(2)D(3) concentrations and decreased plasma 24,25(OH)(2)D(3) concentrations in both large- and small-breed dogs, together with generalized osteoporosis. Large-breed pups fed on a standard diet supplemented with Ca and P had decreased plasma concentrations of both 25(OH)D(3) and 1,25(OH)(2)D(3), which may indicate an increased clearance of these metabolites; the low plasma concentrations of the di-hydroxylated vitamin D metabolites were considered responsible for the disturbance in cartilage maturation (i.e., osteochondrosis) in these dogs. Even lower concentrations of all vitamin D(3) metabolites were seen in young dogs raised on a vitamin D(3)-deficient diet, and led to disturbed osteoid and cartilage mineralization (i.e., rickets). These studies indicate that there is a hierarchy of factors regulating vitamin D(3) metabolism in dogs

  14. FGF23 Regulates Bone Mineralization in a 1,25(OH)2 D3 and Klotho-Independent Manner.

    PubMed

    Murali, Sathish Kumar; Roschger, Paul; Zeitz, Ute; Klaushofer, Klaus; Andrukhova, Olena; Erben, Reinhold G

    2016-01-01

    Fibroblast growth factor-23 (Fgf23) is a bone-derived hormone, suppressing phosphate reabsorption and vitamin D hormone (1,25(OH)2 D3 ) production in the kidney. It has long been an enigma why lack of Fgf23 or of Klotho, the coreceptor for Fgf23, leads to severe impairment in bone mineralization despite the presence of hypercalcemia and hyperphosphatemia. Using Fgf23(-/-) or Klotho(-/-) mice together with compound mutant mice lacking both Fgf23 or Klotho and a functioning vitamin D receptor, we show that in Klotho(-/-) mice the mineralization defect is solely driven by 1,25(OH)2 D3 -induced upregulation of the mineralization-inhibiting molecules osteopontin and pyrophosphate in bone. In Fgf23(-/-) mice, the mineralization defect has two components, a 1,25(OH)2 D3 -driven component similar to Klotho(-/-) mice and a component driven by lack of Fgf23, causing additional accumulation of osteopontin. We found that FGF23 regulates osteopontin secretion indirectly by suppressing alkaline phosphatase transcription and phosphate production in osteoblastic cells, acting through FGF receptor-3 in a Klotho-independent manner. Hence, FGF23 secreted from osteocytes may form an autocrine/paracrine feedback loop for the local fine-tuning of bone mineralization.

  15. 1,25(OH)2D3 Alters Growth Plate Maturation and Bone Architecture in Young Rats with Normal Renal Function

    PubMed Central

    Idelevich, Anna; Kerschnitzki, Michael; Shahar, Ron; Monsonego-Ornan, Efrat

    2011-01-01

    Whereas detrimental effects of vitamin D deficiency are known over century, the effects of vitamin D receptor activation by 1,25(OH)2D3, the principal hormonal form of vitamin D, on the growing bone and its growth plate are less clear. Currently, 1,25(OH)2D3 is used in pediatric patients with chronic kidney disease and mineral and bone disorder (CKD-MBD) and is strongly associated with growth retardation. Here, we investigate the effect of 1,25(OH)2D3 treatment on bone development in normal young rats, unrelated to renal insufficiency. Young rats received daily i.p. injections of 1 µg/kg 1,25(OH)2D3 for one week, or intermittent 3 µg/kg 1,25(OH)2D3 for one month. Histological analysis revealed narrower tibial growth plates, predominantly in the hypertrophic zone of 1,25(OH)2D3-treated animals in both experimental protocols. This phenotype was supported by narrower distribution of aggrecan, collagens II and X mRNA, shown by in situ hybridization. Concomitant with altered chondrocyte maturation, 1,25(OH)2D3 increased chondrocyte proliferation and apoptosis in terminal hypertrophic cells. In vitro treatment of the chondrocytic cell line ATDC5 with 1,25(OH)2D3 lowered differentiation and increased proliferation dose and time-dependently. Micro-CT analysis of femurs from 1-week 1,25(OH)2D3-treated group revealed reduced cortical thickness, elevated cortical porosity, and higher trabecular number and thickness. 1-month administration resulted in a similar cortical phenotype but without effect on trabecular bone. Evaluation of fluorochrome binding with confocal microscopy revealed inhibiting effects of 1,25(OH)2D3 on intracortical bone formation. This study shows negative effects of 1,25(OH)2D3 on growth plate and bone which may contribute to the exacerbation of MBD in the CKD pediatric patients. PMID:21695192

  16. Prospective Investigation of 25(OH)D3 Serum Concentration Following UVB Narrow Band Phototherapy in Patients with Psoriasis and Atopic Dermatitis.

    PubMed

    Weinhold, Annett; Obeid, Rima; Vogt, Thomas; Reichrath, Jörg

    2016-03-01

    Vitamin D deficiency represents a major health issue. It is a worldwide endemic and is associated with a broad variety of severe diseases. The skin is a key tissue for the human body's vitamin D endocrine system. It represents a target tissue for biologically active vitamin D metabolites. Approximately 90% of the human body's requirements of vitamin D have to be synthesised in the skin by the action of UVB-radiation. However, individual factors that influence a person's cutaneous synthesis of vitamin D are still not well understood. In our present prospective study we investigated the effect of UVB narrow band (UVBnb, 311 nm) and PUVA phototherapy on 25(OH)D3 serum concentration, in patients with psoriasis, atopic dermatitis and a few cases with other dermatoses (n=41). We found that two weeks of UVBnb treatment resulted in an increase of 25(OH)D3 serum concentration from 11.4 to 20.5 ng/ml (p<0.001), while in contrast PUVA-treatment did not significantly alter vitamin D status. These findings question the hypothesis of a relevant vitamin D metabolizing effect of UVA. Psoriasis patients showed a trend for a stronger increase in 25(OH)D3 serum levels following UVBnb compared to patients with atopic dermatitis. Patients with relatively low baseline serum 25(OH)D3 concentrations had a stronger increase in 25(OH)D3 concentrations compared to patients with relatively high 25(OH)D serum concentrations. In general patients with skin types (Fitzpatrick) I and II (median=14.3 ng/ml) had a higher baseline of 25(OH)D3 serum concentration compared to patients with skin types III (median=11.2 ng/ml) or IV-V (median=12.3 ng/ml), although these differences were not statistically significant (p=0.106). Baseline 25(OH)D3 serum concentrations were correlated with presence of genetic variants (SNPs of VDR, CYP2R1, VDBP/GC) that influence vitamin D status, and with other individual factors such as body mass index, age and gender. We also investigated the effect of phototherapy on

  17. Prospective Investigation of 25(OH)D3 Serum Concentration Following UVB Narrow Band Phototherapy in Patients with Psoriasis and Atopic Dermatitis.

    PubMed

    Weinhold, Annett; Obeid, Rima; Vogt, Thomas; Reichrath, Jörg

    2016-03-01

    Vitamin D deficiency represents a major health issue. It is a worldwide endemic and is associated with a broad variety of severe diseases. The skin is a key tissue for the human body's vitamin D endocrine system. It represents a target tissue for biologically active vitamin D metabolites. Approximately 90% of the human body's requirements of vitamin D have to be synthesised in the skin by the action of UVB-radiation. However, individual factors that influence a person's cutaneous synthesis of vitamin D are still not well understood. In our present prospective study we investigated the effect of UVB narrow band (UVBnb, 311 nm) and PUVA phototherapy on 25(OH)D3 serum concentration, in patients with psoriasis, atopic dermatitis and a few cases with other dermatoses (n=41). We found that two weeks of UVBnb treatment resulted in an increase of 25(OH)D3 serum concentration from 11.4 to 20.5 ng/ml (p<0.001), while in contrast PUVA-treatment did not significantly alter vitamin D status. These findings question the hypothesis of a relevant vitamin D metabolizing effect of UVA. Psoriasis patients showed a trend for a stronger increase in 25(OH)D3 serum levels following UVBnb compared to patients with atopic dermatitis. Patients with relatively low baseline serum 25(OH)D3 concentrations had a stronger increase in 25(OH)D3 concentrations compared to patients with relatively high 25(OH)D serum concentrations. In general patients with skin types (Fitzpatrick) I and II (median=14.3 ng/ml) had a higher baseline of 25(OH)D3 serum concentration compared to patients with skin types III (median=11.2 ng/ml) or IV-V (median=12.3 ng/ml), although these differences were not statistically significant (p=0.106). Baseline 25(OH)D3 serum concentrations were correlated with presence of genetic variants (SNPs of VDR, CYP2R1, VDBP/GC) that influence vitamin D status, and with other individual factors such as body mass index, age and gender. We also investigated the effect of phototherapy on

  18. TPA decreases 1,25(OH)2D3 binding and calbindin D-28K in renal (MDBK) cells.

    PubMed

    Simboli-Campbell, M; Gagnon, A M; Franks, D J; Welsh, J

    1992-02-01

    The effect of the phorbol ester TPA (12-O-tetradecanoylphorbol 13-acetate) on vitamin D receptors (VDRs) was studied in MDBK cells, a normal bovine renal epithelial cell line. 24 h treatment of MDBK cells with TPA resulted in down-regulation of VDR number, with no change in the binding affinity for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) or approximate molecular weight determined by fast protein liquid chromatography (FPLC). TPA treatment also reduced the level of calbindin D-28K, a vitamin D-dependent renal protein. 4 alpha-Phorbol 12,13-didecanoate (4 alpha-PDD), an inactive phorbol ester, did not affect either 1,25(OH)2D3 binding or calbindin D-28K levels. TPA elicited a significant decrease in membrane-associated protein kinase C (PKC) activity which coincided with the reduction in VDR number and calbindin D-28K. These data support a link between TPA, PKC activity and vitamin D actions in kidney.

  19. Ion microprobe analysis of bone surface elements: Effects of 1,25(OH)2D3

    SciTech Connect

    Bushinsky, D.A.; Chabala, J.M.; Levi-Setti, R. )

    1989-12-01

    When neonatal mouse calvariae are incubated with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) there is net calcium efflux from the bone into the medium. The effect of this enhanced cell-mediated Ca efflux on the relative concentrations of mineral 23Na, 39K, and 40Ca has not previously been studied. We used an imaging scanning ion microprobe, utilizing secondary ion mass spectrometry, to compare the relative ion concentrations of Na, K, and Ca on the surface, subsurface, and cross-section of cultured bone incubated in the presence of 1,25(OH)2D3 with the ion concentrations in similar regions of bone incubated in unaltered control medium. Changes in mineral ion concentration were correlated with net fluxes of Na, K, and Ca relative to bone. Calvariae incubated in control medium (24 h at pH approximately 7.40) have abundant surface Na and K relative to Ca (Na/Ca, 85 and K/Ca, 68), whereas the subsurface has less Na/Ca (21) and K/Ca (23), and on cross section the ratios of both Na/Ca (2.0) and K/Ca (1.9) decrease further. After incubation with 10(-8) M 1,25(OH)2D3, there is a significant increase in bone surface Na/Ca (154) and K/Ca (141) without a change in these ratios on the subsurface and a small fall in both ratios on cross section. The linear relationship between Na/Ca and K/Ca across the three regions of bone observed in control calvariae did not change with 1,25(OH)2D3 treatment. As determined by flux measurements there is a net efflux of Ca but not Na or K from bone.

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

    PubMed Central

    Zhou, Shuanhu; Geng, Shuo; Glowacki, Julie

    2012-01-01

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

  1. Effects of 1α,25-(OH)2D3 on the formation and activity of osteoclasts in RAW264.7 cells.

    PubMed

    Gu, Jianhong; Tong, Xi-Shuai; Chen, Guo-Hong; Wang, Dong; Chen, Yang; Yuan, Yan; Liu, Xue-Zhong; Bian, Jian-Chun; Liu, Zong-Ping

    2015-08-01

    The hormonally active form of vitamin D3, 1α,25-(OH)2D3, has an important role in bone metabolism. This study examined the effects of 1α,25-(OH)2D3 on the ability of two cytokines, receptor activator of nuclear factor-κB ligand (RANKL) and macrophage-colony stimulating factor (M-CSF), to induce RAW 264.7 cells to form osteoclasts. A TRAP histochemical staining assay and bone resorption analysis were used to identify the rate of formation and activity of osteoclasts. The numbers of osteoclasts formed, and their bone resorption activity, was enhanced by the addition of 1α,25-(OH)2D3. The expression levels of osteoclast-specific proteins that are essential for bone resorption, integrin β3, V-ATPase, CAII, CTSK, TRAP and MMP-9, were detected by western blotting. During 48 h, the expression levels of all these proteins significantly increased. Quantitative real-time polymerase chain reaction was used to determine the expression levels of the transcription factors, c-Fos and NFATcl. The expression levels of c-Fos and NFATc1 also increased 24h after treatment with 1α,25-(OH)2D3. These results suggest that 1α,25-(OH)2D3 can regulate bone metabolism by directly enhancing the formation and maturation of osteoclasts.

  2. Low 25-OH vitamin D levels at time of diagnosis and recurrence of ovarian cancer.

    PubMed

    Granato, Teresa; Manganaro, Lucia; Petri, Luca; Porpora, Maria Grazia; Viggiani, Valentina; Angeloni, Antonio; Anastasi, Emanuela

    2016-02-01

    The objective of this study was to evaluate the correlation between 25-OH vitamin D and ovarian cancer as a diagnostic marker or recurrence disease marker. We studied the following: (1) 61 women without gynecologic diseases, (2) 45 women affected by benign ovarian disease, (3) 46 women with recent diagnosis of ovarian cancer, (4) 26 follow-up women with recurrent ovarian cancer, and (5) 32 follow-up women with stable ovarian cancer. The 25-OH vitamin D was quantified with LUMIPULSE® G 25-OH vitamin D on LUMIPULSE® G 1200 (Fujirebio, Japan). As a threshold value, identified by ROC curve analysis, 20.2 ng/mL (sensitivity 73.3 %, specificity 84 %) was chosen corresponding to the limit between sufficient and insufficient 25-OH vitamin D according to the WHO. Low 25-OH vitamin D levels were observed in 26 % of women without gynecologic diseases, in 80 % of women with recent diagnosis of ovarian cancer and in 24 % women affected by benign ovarian diseases (p < 0.001). The follow-up study showed an insufficient level of 25-OH vitamin D in 73 % women with recurrent ovarian cancer and in 47 % women with stable ovarian cancer (p < 0.0003). This study showed that patients with ovarian cancer are often insufficient in 25-OH vitamin D compared to women with benign ovarian diseases. The women with recurrent ovarian cancer presented more often low levels compared to women with stable ovarian cancer. This study suggests that 25-OH vitamin D, due to its antiproliferative properties, can be a good marker for ovarian cancer also.

  3. Effects of intramuscular administration of 1α,25(OH)2D3 during skeletal muscle regeneration on regenerative capacity, muscular fibrosis, and angiogenesis.

    PubMed

    Srikuea, Ratchakrit; Hirunsai, Muthita

    2016-06-15

    The recent discovery of the vitamin D receptor (VDR) in regenerating muscle raises the question regarding the action of vitamin D3 on skeletal muscle regeneration. To investigate the action of vitamin D3 on this process, the tibialis anterior muscle of male C57BL/6 mice (10 wk of age) was injected with 1.2% BaCl2 to induce extensive muscle injury. The bioactive form of vitamin D3 [1α,25(OH)2D3] was administered daily via intramuscular injections during the regenerative phase (days 4-7 postinjury). Physiological and supraphysiological doses of 1α,25(OH)2D3 relative to 1 μg/kg muscle wet weight and mouse body weight were investigated. Muscle samples were collected on day 8 postinjury to examine proteins related to vitamin D3 metabolism (VDR, CYP24A1, and CYP27B1), satellite cell differentiation and regenerative muscle fiber formation [myogenin and embryonic myosin heavy chain (EbMHC)], protein synthesis signaling (Akt, p70 S6K1, 4E-BP1, and myostatin), fiber-type composition (fast and slow MHCs), fibrous formation (vimentin), and angiogenesis (CD31). Administration of 1α,25(OH)2D3 at physiological and supraphysiological doses enhanced VDR expression in regenerative muscle. Moreover, CYP24A1 and vimentin expression was increased, accompanying decreased myogenin and EbMHC expression at the supraphysiological dose. However, there was no change in CYP27B1, Akt, p70 S6K1, 4E-BP1, myostatin, fast and slow MHCs, or CD31 expression at any dose investigated. Taken together, administration of 1α,25(OH)2D3 at a supraphysiological dose decreased satellite cell differentiation, delayed regenerative muscle fiber formation, and increased muscular fibrosis. However, protein synthesis signaling, fiber-type composition, and angiogenesis were not affected by either 1α,25(OH)2D3 administration at a physiological or supraphysiological dose. PMID:27032903

  4. Low 25 (OH) vitamin D levels are associated with autoimmune thyroid disease in polycystic ovary syndrome.

    PubMed

    Muscogiuri, Giovanna; Palomba, Stefano; Caggiano, Mario; Tafuri, Domenico; Colao, Annamaria; Orio, Francesco

    2016-08-01

    Low 25(OH) vitamin D levels have been associated with several autoimmune diseases and recently with autoimmune thyroid disease (AITD). The aim of the study was to investigate the association of AITD with 25(OH) vitamin D levels in women with polycystic ovary syndrome (PCOS). Fifty women with PCOS were consecutively enrolled and underwent routine health checkups, which included measurements of 25(OH) vitamin D, anti-thyroid peroxidase (TPO-Ab), anti-thyreoglobulin (TG-Ab) antibodies, FT3, FT4, and TSH. Selecting 50 nmol/L as cut-off point, low 25(OH) vitamin D levels were detected in 23 of 50 patients (46 %). AITD was diagnosed when TPO-Ab levels exceeding 80 U/ml and/or TG-Ab levels exceeding 70 U/ml. AITD was detected in 12 of 50 patients (24 %). The levels of 25(OH) vitamin D were significantly lower in women with PCOS and AITD when compared with women with PCOS and without AITD (p = 0.02). In women with AITD no correlation was found between 25(OH) vitamin D and TG-Ab (r = 0.48; p = 0.16), TPO-Ab (r = 0.43; p = 0.21), TSH (r = 0.38; p = 0.27), FT3 (r = -0.40; p = 0.25) and FT4 levels (r = -0.54; p = 0.10). These findings suggest that low levels of 25(OH) vitamin D were significantly associated with AITD in women with PCOS.

  5. Administration of exogenous 1,25(OH)2D3 normalizes overactivation of the central renin-angiotensin system in 1α(OH)ase knockout mice.

    PubMed

    Zhang, Wei; Chen, Lulu; Zhang, Luqing; Xiao, Ming; Ding, Jiong; Goltzman, David; Miao, Dengshun

    2015-02-19

    Previously, we reported that active vitamin D deficiency in mice causes secondary hypertension and cardiac dysfunction, but the underlying mechanism remains largely unknown. To clarify whether exogenous active vitamin D rescues hypertension by normalizing the altered central renin-angiotensin system (RAS) via an antioxidative stress mechanism, 1-alpha-hydroxylase [1α(OH)ase] knockout mice [1α(OH)ase(-/-)] and their wild-type littermates were fed a normal diet alone or with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or a high-calcium, high-phosphorus "rescue" diet with or without antioxidant N-acetyl-l-cysteine (NAC) supplementation for 4 weeks. Compared with their wild-type littermates, 1α(OH)ase(-/-)mice had high mean arterial pressure, increased levels of renin, angiotensin II (Ang II), and Ang II type 1 receptor, and increased malondialdehyde levels, but decreased anti-peroxiredoxin I and IV proteins and the antioxidative genes glutathione reductase (Gsr) and glutathione peroxidase 4 (Gpx4) in the brain samples. Except Ang II type 1 receptor, these pathophysiological changes were rescued by exogenous 1,25(OH)2D3 or NAC plus rescue diet, but not by rescue diet alone. We conclude that 1,25(OH)2D3 normalizes the altered central RAS in 1α(OH)ase(-/-)mice, at least partially, through a central antioxidative mechanism.

  6. Effects of sun exposure on 25(OH) vitamin D concentration in urban and rural women in Malaysia.

    PubMed

    Nurbazlin, Musa; Chee, Winnie Siew Swee; Rokiah, Pendek; Tan, Alexander Tong Boon; Chew, Yee Yean; Nusaibah, Abd Rahman Siti; Chan, Siew Pheng

    2013-01-01

    Ultraviolet B sunlight exposure is a primary source of vitamin D. There have been reports of low vitamin D status amongst the Malaysian population despite it being a tropical country. This study was conducted to determine the influence of sun exposure on 25(OH)D concentrations in urban and rural women in Malaysia and factors predicting 25(OH)D concentrations. Women aged above 45 years were recruited from urban (n=107) and rural areas (n=293). Subjects were interviewed regarding their outdoor activities and usual outdoor attire over the previous week. 25(OH)D concentrations were analyzed using the vitamin D3 (25-OH) electrochemiluminescence immunoassay. Median (Q1-Q3) age of the participants was 57 (53-61) years old. Median (Q1-Q3) 25(OH)D concentration of rural women was significantly higher [69.5 (59.0-79.1) nmol/L] compared to urban women [31.9 (26.1- 45.5) nmol/L] (p<0.001). Rural women spent more time in the sun compared to urban women (7.83 (3.67-14.7) vs 2.92 (1.17-4.92) hours, p<0.001), although the fraction of body surface area (BSA) exposed to sunlight was significantly higher in the urban group [0.21 (0.21-0.43) vs 0.12 (0.07-0.17), p<0.001]. The calculated sun index (hours of sun exposure per week × fraction of BSA) was significantly higher in rural [0.89 (0.42-1.83)] compared to urban women [0.72 (0.26-1.28)], p=0.018. In the stepwise linear regression, rural dwelling increased the serum 25(OH)D by 31.74 nmol/L and 25(OH)D concentrations increased by 1.93 nmol/L for every unit increment in sun index. Urban women in Malaysia had significantly lower vitamin D status compared to rural women. Rural dwelling and sun index were key factors influencing vitamin D status in Malaysian women.

  7. Modulation of 1alpha,25-dihydroxyvitamin D3-membrane associated, rapid response steroid binding protein expression in mouse odontoblasts by 1alpha,25-(OH)2D3.

    PubMed

    Teillaud, Christophe; Nemere, Ilka; Boukhobza, Florine; Mathiot, Claire; Conan, Nicole; Oboeuf, Martine; Hotton, Dominique; Macdougall, Mary; Berdal, Ariane

    2005-01-01

    The rapid, nongenomic effects of 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3 have been related to a 1,25D3-membrane associated, rapid response steroid binding protein or 1,25D3-[MARRS]bp, with a molecular weight of 65 kDa, in several tissues and species. Currently, no information is available concerning the nongenomic responses to 1alpha,25-(OH)2D3 in dental tissues. In order to investigate the expression of 1,25D3-[MARRS]bp in dental cells, in the presence or absence of 1alpha,25-(OH)2D3, we have used rabbit polyclonal antibodies directed against the N-terminus of the 1,25D3-[MARRS]bp (Ab099) that recognizes the 1alpha,25-(OH)2D3 binding protein in chick intestinal basolateral membranes and a mouse odontoblast-like cell line (MO6-G3). Western blotting and flow cytometric analyses with Ab099 specifically detected 1,25D3-[MARRS]bp in MO6-G3 cells. Moreover, 1,25D3-[MARRS]bp was up-regulated, in vivo, in differentiated dental cells. Electron microscopic analysis confirmed the plasma membrane localization of this binding protein and also showed its intracellular presence. Incubation of MO6-G3 cells with different doses of 1alpha,25-(OH)2D3 for 36 h resulted in an inhibition of 1,25D3-[MARRS]bp expression with a maximal effect at 50 nM steroid. In addition, the culture media of MO6-G3 cells contains immunoreactive 1,25D3-[MARRS]bp. Immunogold positive membrane vesicle-like structures are present in the extracellular matrix of MO6-G3 cells. Altogether, these results indicate that the 1,25D3-[MARRS]bp expression in MO6-G3 cells is modulated by 1alpha,25-(OH)2D3. In conclusion, this 1alpha,25-(OH)2D3 binding protein could play an important role in the rapid, nongenomic responses to 1alpha,25-(OH)2D3 in dental cells.

  8. Super pharmacological levels of calcitriol (1,25-(OH)2D3) inhibits mineral deposition and decreases cell proliferation in a strain dependent manner in chicken mesenchymal stem cells undergoing osteogenic differentiation in vitro

    PubMed Central

    Pande, Vivek V.; Chousalkar, Kapil C.; Bhanugopan, Marie S.; Quinn, Jane C.

    2015-01-01

    The biologically active form of vitamin D3, calcitriol (1,25-(OH)2D3), plays a key role in mineral homeostasis and bone formation and dietary vitamin D3 deficiency is a major cause of bone disorders in poultry. Supplementary dietary cholecalciferol (25-hydroxyvitamin D, 25-OH), the precursor of calcitriol, is commonly employed to combat this problem; however, dosage must be carefully determined as excess dietary vitamin D can cause toxicity resulting in a decrease in bone calcification, hypercalcinemia and renal failure. Despite much research on the therapeutic administration of dietary vitamin D in humans, the relative sensitivity of avian species to exogenous vitamin D has not been well defined. In order to determine the effects of exogenous 1,25-(OH)2D3 during avian osteogenesis, chicken bone marrow-derived mesenchymal stem cells (BM-MSCs) were exposed to varying doses of 1,25-(OH)2D3 during in vitro osteogenic differentiation and examined for markers of early proliferation and osteogenic induction. Similar to humans and other mammals, poultry BM-MSCs were found to be highly sensitive to exogenous 1,25-(OH)2D3 with super pharmacological levels exerting significant inhibition of mineralization and loss of cell proliferation in vitro. Strain related differences were apparent, with BM-MCSs derived from layers strains showing a higher level of sensitivity to 1,25-(OH)2D3 than those from broilers. These data suggest that understanding species and strain specific sensitivities to 1,25-(OH)2D3 is important for optimizing bone health in the poultry industry and that use of avian BM-MSCs are a useful tool for examining underlying effects of genetic variation in poultry. PMID:26500277

  9. Differential response to 1α, 25-dihydroxyvitamin D3 (1α,25(OH)2D3) in non-small cell lung cancer cells with distinct oncogene mutations1

    PubMed Central

    Zhang, Qiuhong; Kanterewicz, Beatriz; Shoemaker, Suzanne; Hu, Qiang; Liu, Song; Atwood, Kristopher; Hershberger, Pamela

    2012-01-01

    We previously demonstrated that non-small cell lung cancer (NSCLC) cells and primary human lung tumors aberrantly express the vitamin D3-catabolizing enzyme, CYP24, and that CYP24 restricts transcriptional regulation and growth control by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) in NSCLC cells. To ascertain the basis for CYP24 dysregulation, we assembled a panel of cell lines that represent distinct molecular classes of lung cancer: Cell lines were selected which harbored mutually exclusive mutations in either the K-ras or the Epidermal Growth Factor Receptor (EGFR) genes. We observed that K-ras mutant lines displayed a basal vitamin D receptor (VDR)lowCYP24high phenotype, whereas EGFR mutant lines had a VDRhighCYP24low phenotype. A mutation-associated difference in CYP24 expression was also observed in clinical specimens. Specifically, K-ras mutation was associated with a median 4.2-fold increase in CYP24 mRNA expression (p = 4.8 × 10−7) compared to EGFR mutation in a series of 147 primary lung adenocarcinoma cases. Because of their differential basal expression of VDR and CYP24, we hypothesized that NSCLC cells with an EGFR mutation would be more responsive to 1,25(OH)2D3 treatment than those with a K-ras mutation. To test this, we measured the ability of 1,25(OH)2D3 to increase reporter gene activity, induce transcription of endogenous target genes, and suppress colony formation. In each assay, the extent of 1,25(OH)2D3 response was greater in EGFR mutation-positive HCC827 and H1975 cells than in K-ras mutation-positive A549 and 128.88T cells. We subsequently examined the effect of combining 1,25(OH)2D3 with erlotinib, which is used clinically in the treatment of EGFR mutation-positive NSCLC. 1,25(OH)2D3/erlotinib combination resulted in significantly greater growth inhibition than either single agent in both the erlotinib-sensitive HCC827 cell line and the erlotinib-resistant H1975 cell line. These data are the first to suggest that EGFR mutations may

  10. 1,25(OH)2D3 Deficiency Induces Colon Inflammation via Secretion of Senescence-Associated Inflammatory Cytokines

    PubMed Central

    Zhi, Chunchun; Shen, Ming; Sun, Weiwei; Miao, Dengshun; Yuan, Xiaoqin

    2016-01-01

    Epidemiological studies showed that 1,25-Dihydroxyvitamin D[1,25(OH)2D3] insufficiency appears to be associated with aging and colon cancer while underlying biological mechanisms remain largely unknown. Inflammatory bowel disease is one of the risk factors for colon cancer. In this study, we investigated whether 1,25(OH)2D3 deficiency has an impact on the colon of 25-hydroxyvitamin D 1α-hydroxylase knockout [Cyp27b1−/−] mice fed on a rescue diet (high calcium, phosphate, and lactose) from weaning to 10 months of age. We found that 1,25(OH)2D3 deficient mice displayed significant colon inflammation phenotypes including shortened colon length, thinned and disordered mucosal structure, and inflammatory cell infiltration. DNA damage, cellular senescence and the production of senescence-associated inflammatory cytokines were also increased significantly in the colon of Cyp27b1−/−mice. Furthermore, the levels of ROS in the colon were increased significantly, whereas the expression levels of antioxidative genes were down-regulated dramatically in the colon of Cyp27b1−/−mice. Taken together, our results demonstrated that 1,25(OH)2D3 deficiency could induce colon inflammation, which may result from increased oxidative stress and DNA damage, subsequently, induced cell senescence and overproduction of senescence-associated secretory factors. Therefore, our findings suggest that 1,25(OH)2D3 may play an important role in preventing the development and progression of colon inflammation and colon cancer. PMID:26790152

  11. Reduced 25-OH vitamin D in patients with autoimmune cytopenias, clinical correlations and literature review.

    PubMed

    Fattizzo, Bruno; Zaninoni, Anna; Giannotta, Juri A; Binda, Francesca; Cortelezzi, Agostino; Barcellini, Wilma

    2016-07-01

    Vitamin D deficiency is widespread in Western Countries and has been found related to autoimmune and hematologic disease incidence and clinical course. We evaluated vitamin D levels, vitamin D receptor (VDR) and T helper (Th)1, Th2 and Th17 immunomodulatory cytokines in patients with immune thrombocytopenic purpura (ITP, N=44), primary autoimmune hemolytic anemia (AIHA, n=35), Evans' syndrome (n=5) and chronic idiopathic neutropenia (CIN, n=19) and also tested vitamin D effect on the in vitro production of anti-erythrocyte autoantibodies. 25-OH-vitamin D levels were significantly lower and vitamin D receptor higher in patients than in controls. Among ITP cases, those with very low vitamin D levels displayed reduced platelet counts, irrespective of the bleeding history. In AIHA patients, LDH values negatively correlated with vitamin D levels in mixed forms, and reticulocyte counts were positively related with vitamin D. Considering treatment, AIHA patients who had been treated with 2 therapy lines or more showed lower mean 25-OH-vitamin D levels than those untreated or treated with one line of therapy only. IL-6, IL-10, IL-17 and IFN-γ levels were higher in patients versus controls, whereas TNF-α was significantly reduced. Finally, vitamin D at concentrations of 10, 20, and 40ng/mL reduced the in vitro production of anti-erythrocyte autoantibodies both in pokeweed-stimulated and unstimulated cultures. In conclusion, vitamin D is reduced in autoimmune cytopenias and correlate with disease severity, supporting its possible protective role against the development of autoimmunity. Literature review showed vitamin D deficiency reports both in onco- and in non onco-hematologic diseases with a relationship with disease severity/activity in myeloid and lymphoid neoplasms, as well as in sickle cell disease. Supplementation has produced weak results in autoimmune and hematologic diseases, and further studies are needed.

  12. Optimal Dose of Vitamin D3 400 I.U. for Average Adults has A Significant Anti-Cancer Effect, While Widely Used 2000 I.U. or Higher Promotes Cancer: Marked Reduction of Taurine & 1α, 25(OH)2D3 Was Found In Various Cancer Tissues and Oral Intake of Optimal Dose of Taurine 175mg for Average Adults, Rather Than 500mg, Was Found to Be A New Potentially Safe and More Effective Method of Cancer Treatment.

    PubMed

    Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

    2016-01-01

    During the past 10 years, the author had found that the optimal dose of Vitamin D3 400 I.U. has safe & effective anticancer effects, while commonly used 2000-5000 I.U. of Vit. D3 often creates a 2-3 time increase in cancer markers. We examined the concentration of Taurine in normal internal organs and in cancer using Bi-Digital O-Ring Test. We found that Taurine levels in normal tissue are 4-6ng. But, the amount of Taurine of average normal value of 5.0-5.25ng was strikingly reduced to 0.0025-0.0028ng in this study of several examples in adenocarcinomas of the esophagus, stomach, pancreas, colon, prostate, and lung, as well as breast cancer. The lowest Taurine levels of 0.0002-0.0005ng were found in so called Zika virus infected babies from Brazil with microcephaly. While Vitamin D3 receptor stimulant 1α, 25 (OH)2D3 in normal tissues was 0.45-0.53ng, they were reduced to 0.025-0.006ng in cancers (1/100th-1/200th of normal value), particularly in various adenocarcinomas. All of these adenocarcinomas had about 1500ng HPV-16 viral infection. In 500 breast cancers, about 97% had HPV-16. The optimal dose of Taurine for average adult has been found to be about 175mg, rather than the widely used 500mg. In addition, since Taurine is markedly reduced to close to 1/1000th-1/2000th of its normal value in these cancer tissues, we examined the effect of the optimal dose of Taurine on cancer patients. Optimal dose of Taurine produced a very significant decrease in cancer-associated parameters, such as Oncogene C-fosAb2 & Integrin α5β1 being reduced to less than 1/1,000th, and 8-OH-dG (which increases in the presence of DNA mutation) reduced to less than 1/10th. The optimal dose of Taurine 175mg for average adult various cancer patient 3 times a day alone provide beneficial effects with very significant anti-cancer effects with strikingly increased urinary excretion of bacteria, viruses, & funguses, asbestos, toxic metals & other toxic substances. However, optimal doses of

  13. Optimal Dose of Vitamin D3 400 I.U. for Average Adults has A Significant Anti-Cancer Effect, While Widely Used 2000 I.U. or Higher Promotes Cancer: Marked Reduction of Taurine & 1α, 25(OH)2D3 Was Found In Various Cancer Tissues and Oral Intake of Optimal Dose of Taurine 175mg for Average Adults, Rather Than 500mg, Was Found to Be A New Potentially Safe and More Effective Method of Cancer Treatment.

    PubMed

    Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

    2016-01-01

    During the past 10 years, the author had found that the optimal dose of Vitamin D3 400 I.U. has safe & effective anticancer effects, while commonly used 2000-5000 I.U. of Vit. D3 often creates a 2-3 time increase in cancer markers. We examined the concentration of Taurine in normal internal organs and in cancer using Bi-Digital O-Ring Test. We found that Taurine levels in normal tissue are 4-6ng. But, the amount of Taurine of average normal value of 5.0-5.25ng was strikingly reduced to 0.0025-0.0028ng in this study of several examples in adenocarcinomas of the esophagus, stomach, pancreas, colon, prostate, and lung, as well as breast cancer. The lowest Taurine levels of 0.0002-0.0005ng were found in so called Zika virus infected babies from Brazil with microcephaly. While Vitamin D3 receptor stimulant 1α, 25 (OH)2D3 in normal tissues was 0.45-0.53ng, they were reduced to 0.025-0.006ng in cancers (1/100th-1/200th of normal value), particularly in various adenocarcinomas. All of these adenocarcinomas had about 1500ng HPV-16 viral infection. In 500 breast cancers, about 97% had HPV-16. The optimal dose of Taurine for average adult has been found to be about 175mg, rather than the widely used 500mg. In addition, since Taurine is markedly reduced to close to 1/1000th-1/2000th of its normal value in these cancer tissues, we examined the effect of the optimal dose of Taurine on cancer patients. Optimal dose of Taurine produced a very significant decrease in cancer-associated parameters, such as Oncogene C-fosAb2 & Integrin α5β1 being reduced to less than 1/1,000th, and 8-OH-dG (which increases in the presence of DNA mutation) reduced to less than 1/10th. The optimal dose of Taurine 175mg for average adult various cancer patient 3 times a day alone provide beneficial effects with very significant anti-cancer effects with strikingly increased urinary excretion of bacteria, viruses, & funguses, asbestos, toxic metals & other toxic substances. However, optimal doses of

  14. Stimulation of zinc transport Caco2 cells by 1,25(OH) sub 2 vitamin D sub 3

    SciTech Connect

    Fleet, J.C.; Bourcier, M.; Turnbull, A.J.; Wood, R.J. )

    1991-03-15

    Evidence exists which suggests that 1,25(OH){sub 2} vitamin D{sub 3} (D3) may stimulate zinc (Zn) absorption in animals and man. The authors have studied this phenomenon by assessing Zn transport across monolayers of the human adenocarcinoma cell line, Caco2. This model has been used previously to examine Zn transport kinetics in vitro. Cells for 18 d and then treated with 10 nM D3 for 3 d transported more Zn than controls when each were incubated with 100 uM Zn for 60 min. Excess calcium, added during the transport study, inhibited both basal and D3-stimulated Zn transport equally, indicating the additional Zn was not transported through the D3-stimulated calcium pathway. Metallothionein mRNA levels increased slowly and progressively in response to 10 nM D3. Quinacrine, a lysosome disrupting agent, when added to the transport buffer 30 min prior to the transport study, completely inhibited D3-stimulated Zn transport. Basal Zn transport was reduced 60% by quinacrine suggesting a lysosomal component to both basal and D3-stimulated Zn transport. These data demonstrate that D3 stimulates a unique Zn transport system which may involve both lysosomes and metallothionein.

  15. Changes of 25-OH-Vitamin D during Overwintering at the German Antarctic Stations Neumayer II and III

    PubMed Central

    Steinach, Mathias; Kohlberg, Eberhard; Maggioni, Martina Anna; Mendt, Stefan; Opatz, Oliver; Stahn, Alexander; Tiedemann, Josefine; Gunga, Hanns-Christian

    2015-01-01

    Purpose Humans in Antarctica face different environmental challenges, such as low ultra-violet radiation, which is crucial for vitamin D production in humans. Therefore we assessed changes in 25-OH-vitamin D serum concentration during 13 months of overwintering at the German Stations Neumayer II and III (2007–2012). We hypothesized that (i) 25-OH-vitamin D serum concentration would significantly decrease, (ii) changes would be affected by age, gender, baseline (i.e. pre-overwintering) fat mass, baseline 25-OH-vitamin D serum concentration, and station residence, and (iii) our results would not differ from similar previous studies in comparable high latitudes. Materials & Methods 25-OH-vitamin D serum concentrations were determined before, after, and monthly during the campaigns from venous blood samples of n = 43 participants (28 men, 15 women). Baseline fat mass was determined via bio impedance analysis and body plethysmography. Data were analyzed for change over time, dependency on independent parameters, and after categorization for sufficiency (>50nmol/l), insufficiency (25-50nmol/l), and deficiency (<25nmol/l). Results were compared with data from similar previous studies. Results We found a significant decrease of 25-OH-vitamin D with dependency on month. Age, gender, fat mass, and station residence had no influence. Only baseline 25-OH-vitamin D serum concentrations significantly affected subsequent 25-OH-vitamin D values. Conclusions Overwinterings at the Antarctic German research stations Neumayer II and III are associated with a decrease in 25-OH-vitamin D serum concentrations, unaffected by age, gender, baseline fat mass, and station residence. Higher baseline vitamin D serum concentrations might protect from subsequent deficiencies. Residence at the Neumayer Stations may lead to lower vitamin D serum concentrations than found in other comparable high latitudes. PMID:26641669

  16. Association Between Serum 25(OH) Vitamin D and the Risk of Cognitive Decline in Older Women

    PubMed Central

    Paudel, Misti; Taylor, Brent C.; Ishani, Areef; Rossom, Rebecca; Yaffe, Kristine; Blackwell, Terri; Lui, Li-Yung; Hochberg, Marc; Ensrud, Kristine E.

    2012-01-01

    Background: Results of prospective studies examining the association between 25 hydroxyvitamin D (25[OH]D) levels and cognitive decline have been inconsistent. We tested the hypothesis that lower 25(OH)D levels are associated with a greater likelihood of cognitive impairment and risk of cognitive decline. Methods: The study is a cross-sectional and longitudinal analysis of a prospective cohort of 6,257 community-dwelling elderly women followed for 4 years. Global cognitive function was measured by the Modified Mini-Mental State Examination and executive function was measured by Trail Making Test Part B (Trails B). Cognitive impairment at baseline was defined as a score >1.5 SD below the sample mean; cognitive decline was defined as decline from baseline to follow-up >1 SD from mean change in score. Results: Women with very low vitamin D levels had an increased odds of global cognitive impairment at baseline: odds ratio (95% confidence interval), 1.60 (1.05–2.42) for women with 25(OH)D <10 ng/mL (25 nmol/L) compared with those with 25(OH)D levels ≥30 ng/mL (75 nmol/L). Compared with women with baseline 25(OH)D level ≥30 ng/mL (75 nmol/L), women with lower levels had an increased risk of global cognitive decline: odds ratio (95% confidence interval), 1.58(1.12–2.22) for women with levels <10 ng/mL (25 nmol/L), and 1.31 (1.04–1.64) for those with levels 10–19.9 ng/mL (25–49 nmol/L). Levels of 25(OH)D were not associated with executive cognitive function. Conclusions: Low 25(OH)D levels among older women were associated with a higher odds of global cognitive impairment and a higher risk of global cognitive decline. PMID:22454371

  17. TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis.

    PubMed

    Bucova, Maria; Suchankova, Magda; Tibenska, Elena; Tedlova, Eva; Demian, Juraj; Majer, Ivan; Novosadova, Helena; Tedla, Miroslav

    2015-01-01

    TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels.

  18. TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis

    PubMed Central

    Bucova, Maria; Suchankova, Magda; Tibenska, Elena; Tedlova, Eva; Demian, Juraj; Majer, Ivan; Novosadova, Helena; Tedla, Miroslav

    2015-01-01

    TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels. PMID:26166951

  19. TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis.

    PubMed

    Bucova, Maria; Suchankova, Magda; Tibenska, Elena; Tedlova, Eva; Demian, Juraj; Majer, Ivan; Novosadova, Helena; Tedla, Miroslav

    2015-01-01

    TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels. PMID:26166951

  20. Histochemical examination of the effects of high-dose 1,25(OH)2D3 on bone remodeling in young growing rats.

    PubMed

    Sun, Jing; Sun, Bao; Wang, Wei; Han, Xiuchun; Liu, Hongrui; Du, Juan; Feng, Wei; Liu, Bo; Amizuka, Norio; Li, Minqi

    2016-08-01

    Vitamin D has an anabolic effect on bone developmental processes and is involved in maintaining skeletal integrity. In recent years, pediatric cases of vitamin D intoxication have attracted attention. Therefore, the aim of this study was to investigate the influence of long-term administration of physiologically-high-dose calcitriol (1,25(OH)2D3) on bone remodeling in young developing rats. Neonatal rats received once-daily subcutaneous injection of calcitriol (250 ng/kg body weight), or PBS only as a control, for 3 weeks. At 1, 2 and 4 weeks' post-administration, rats were sacrificed and fixed by transcardial perfusion with 4 % paraformaldehyde, following which tibiae were extracted for histochemical analysis. Compared with the control group, the number of tartrate-resistant acid phosphatase- and Cathepsin K-positive osteoclasts were significantly increased, and the expression of alkaline phosphatase in osteoblasts was decreased in trabecular bone of rats administered high-dose 1,25(OH)2D3, leading to decreased trabecular bone volume. In addition, the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) was increased, while that of osteoprotegerin was weaker in osteoblasts in the experimental group compared with the control group. Moreover, there was weaker immunoreactivity for EphrinB2 in osteoclasts and EphB4 in osteoblasts of trabecular bone in the experimental group compared with the control group. These findings suggest that long-term use of physiologically-high dose calcitriol may result in bone loss through RANKL/RANK/osteoprotegerin and EphrinB2-EphB4 signaling pathways, and that these negative effects could continue after drug withdrawal. Therefore, optimal limits for vitamin D administration need to be established for children and adolescents. PMID:27255234

  1. Serum 25(OH) Vitamin D Levels in Polish Women during Pregnancies Complicated by Hypertensive Disorders and Gestational Diabetes

    PubMed Central

    Domaracki, Piotr; Sadlecki, Pawel; Odrowaz-Sypniewska, Grazyna; Dzikowska, Ewa; Walentowicz, Pawel; Siodmiak, Joanna; Grabiec, Marek; Walentowicz-Sadlecka, Malgorzata

    2016-01-01

    Background: An association between the level of vitamin D and the risk of pregnancy-related complications remains unclear. The aim of this study was to examine concentrations of 25(OH) vitamin D in Polish women with normal pregnancies and pregnancies complicated by gestational hypertension, preeclampsia or gestational diabetes mellitus (GDM). Moreover, we analyzed an association between maternal serum 25(OH)D and the risk of gestational hypertension, preeclampsia and GDM. Material and Methods: The study included 207 pregnant women, among them 171 with pregnancy-related complications: gestational hypertension (n = 45), preeclampsia (n = 23) or GDM (n = 103). The control group consisted of 36 women with normal pregnancies. Concentrations of serum 25(OH)D were measured at admission to the hospital prior to delivery Results: Patients with hypertension did not differ significantly from the controls in terms of their serum 25(OH)D concentrations (18.20 vs. 22.10 ng/mL, p = 0.15). Highly significant differences were found in 25(OH)D concentrations of women with preeclampsia and the controls (14.75 vs. 22.10 ng/mL, p = 0.0021). GDM was not associated with significant differences in 25(OH)D concentration. A low level of 25(OH)D turned out to be associated with an increased risk of preeclampsia during pregnancy on both univariate and multivariate regression analysis, and was a significant predictor of this condition on ROC (receiver operating characteristic) analysis (AUC = 0.70, p < 0.01). Conclusions: 25(OH)D deficiency is common among pregnant Polish women. Low concentrations of 25(OH)D may play a role in the etiopathogenesis of preeclampsia. Routine assessment of the 25(OH)D level during pregnancy may be crucial for the identification of women at increased risk of preeclampsia. PMID:27690002

  2. New perspectives on vitamin D food fortification based on a modeling of 25(OH)D concentrations

    PubMed Central

    2013-01-01

    Background In Germany, vitamin D intake from food and synthesis in the skin is low, which leads to low 25(OH)D serum concentrations. In contrast to many other countries, general vitamin D food fortification is still prohibited in Germany, although the European Commission published a regulatory framework to harmonize addition of vitamins to foods. Thus the purpose of our study was to develop a vitamin D fortification model, taking into account all vitamin D sources with the goal to fulfill requirements of intake recommendations or preferable 25(OH)D serum concentrations. Finally, the aim was to assess the suitability of different carriers and associated risks. Methods We developed a mathematical bottom-up model of 25(OH)D serum concentrations based on data about vitamin D sources of the German population such as sunlight, food and supplements for all federal states taking seasonal and geographical variations into account. We used this model to calculate the optimal fortification levels of different vitamin D carriers in two approaches. First we calculated required fortification levels based on fixed intake recommendations from e.g. the IOM or the DGE and second based on achieving certain 25(OH)D serum concentrations. Results To lift 25(OH)D serum concentration in Germany to 75 nmol/L, e.g. 100 g bread has to be fortified with 11.3 μg during winter, resulting in a daily vitamin D intake of 23.7 μg. Bread seems to be a suitable carrier for base supply. However, overdose risk with a single fortified product is higher than the risk with several fortified carriers. Conclusions With the model in hand, it is possible to conceive vitamin D fortification strategies for different foodstuffs and model its impact on 25(OH)D serum concentrations. PMID:24261676

  3. 1α,25(OH)2D3 Suppresses the Migration of Ovarian Cancer SKOV-3 Cells through the Inhibition of Epithelial–Mesenchymal Transition

    PubMed Central

    Hou, Yong-Feng; Gao, Si-Hai; Wang, Ping; Zhang, He-Mei; Liu, Li-Zhi; Ye, Meng-Xuan; Zhou, Guang-Ming; Zhang, Zeng-Li; Li, Bing-Yan

    2016-01-01

    Ovarian cancer is the most lethal gynecological malignancy due to its high metastatic ability. Epithelial-mesenchymal transition (EMT) is essential during both follicular rupture and epithelium regeneration. However, it may also accelerate the progression of ovarian carcinomas. Experimental studies have found that 1α,25-dihydroxyvitamin-D3 [1α,25(OH)2D3] can inhibit the proliferation of ovarian cancer cells. In this study, we investigated whether 1α,25(OH)2D3 could inhibit the migration of ovarian cancer cells via regulating EMT. We established a model of transient transforming growth factor-β1(TGF-β1)-induced EMT in human ovarian adenocarcinoma cell line SKOV-3 cells. Results showed that, compared with control, 1α,25(OH)2D3 not only inhibited the migration and the invasion of SKOV-3 cells, but also promoted the acquisition of an epithelial phenotype of SKOV-3 cells treated with TGF-β1. We discovered that 1α,25(OH)2D3 increased the expression of epithelial marker E-cadherin and decreased the level of mesenchymal marker, Vimentin, which was associated with the elevated expression of VDR. Moreover, 1α,25(OH)2D3 reduced the expression level of transcription factors of EMT, such as slug, snail, and β-catenin. These results indicate that 1α,25(OH)2D3 suppresses the migration and invasion of ovarian cancer cells by inhibiting EMT, implying that 1α,25(OH)2D3 might be a potential therapeutic agent for the treatment of ovarian cancer. PMID:27548154

  4. Association between promoter region genetic variants of PTH SNPs and serum 25(OH)-vitamin D level

    PubMed Central

    Al-Daghri, Nasser M; Al-Attas, Omar S; Krishnaswamy, Soundararajan; Yakout, Sobhy M; Mohammed, Abdul Khader; Alenad, Amal M; Chrousos, George P; Alokail, Majed S

    2015-01-01

    Parathyroid hormone (PTH) plays a crucial role in calcium metabolism and skeletal development via altering vitamin D level. Besides, hypersecretion of PTH is implicated in the etiology of osteoporosis. In this study, we analyzed association between promoter region sequence variants of PTH gene and circulating 25-hydroxy-vitamin D (25(OH)D) level. Genotypes of PTH SNPs rs1459015, rs10500783 and rs10500784 and circulating serum 25(OH)D level of healthy adults (N=386) of different nationalities living in Riyadh were determined and relation between the different PTH allelic variants and corresponding mean 25(OH)D values were obtained using Analysis of Variance (ANOVA) and Bonferroni post-hoc test for multiple comparisons. We observed a high prevalence of vitamin D deficiency (<50 nmol/l) among all nationals which ranged from 59% among Indians to 82% among Yemeni. Comparison of the means of 25(OH)D levels corresponding to different genotypes of PTH SNPs indicated that the T allele of SNP rs1459015 was associated with higher 25(OH)D level in the Sudanese (P=0.03), while the T allele of SNP rs10500783 was associated with higher 25(OH)D level in Saudis (P=0.03). Analysis of results also indicated that the Sudanese carriers of the CC genotype of SNP rs1459015 had a higher risk of suffering from vitamin D deficiency (P=0.02). In conclusion, our study indicated significant association between specific PTH gene promoter region variants and altered levels of 25(OH)D and vitamin D deficiency among specific nationals. PMID:26339419

  5. Effects of 25-(OH)D3 on fecal Ca and P excretion, bone mineralization, Ca and P transporter mRNA expression and performance in growing female pigs.

    PubMed

    Regassa, Alemu; Adhikari, Roshan; Nyachoti, Charles M; Kim, Woo Kyun

    2015-01-01

    A study was conducted to examine the effects of 25-hydroxyvitamin D3 (25-(OH)D3) on fecal Ca and P excretion, bone mineralization, performance and the mRNA expression of intestinal transporter genes in growing female pigs. Sixty-day old gilts (n = 24) with an average initial BW of 23.13 ± 1.49 kg were randomly allocated to a control diet (diet 1) containing wheat/corn/soybean meal and 150 IU kg(-1) of Vitamin D3, diet 1 + 50 μg of 25-(OH)D3 kg(-1) (diet 2) and diet 1 + 100 μg of 25-(OH)D3 kg(-1) (diet 3). The pigs were housed in an individual pen and had ad libitum access to feed and water for 42 days, and BWG and feed intake were measured weekly. Measures of bone mineralization and expression of Ca and P transporters mRNA were analyzed using Dual Energy X-Ray Absortiometry (DEXA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Data were analyzed using GLM procedure of the Statistical Analysis System (SAS Institute version 9.2). Fecal Ca and P concentration were significantly reduced (P ≤ 0.05) in pigs fed diets 2 and 3 compared with the control diet. Supplementation of 25-(OH)D3 did not significantly improve bone mineralization, animal performance and intestinal transporters mRNA expression except for SLC34A1, a sodium-dependent phosphate transporter 1. In conclusion, supplementation of 25-(OH)D3 in swine nutrition may not improve animal performance but has the potential to reduce environmental pollution by increasing dietary Ca and P retention while reducing their excretion.

  6. 1,25 (OH)2D3 enhances PTH-induced Ca2+ transients in preosteoblasts by activating L-type Ca2+ channels

    NASA Technical Reports Server (NTRS)

    Li, W.; Duncan, R. L.; Karin, N. J.; Farach-Carson, M. C.

    1997-01-01

    We previously demonstrated electrophysiologically that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] shifts the activation threshold of L-type Ca2+ channels in osteoblasts toward the resting potential and prolongs mean open time. Presently, we used single-cell Ca2+ imaging to study the combined effects of 1,25(OH)2D3 and parathyroid hormone (PTH) during generation of Ca2+ transients in fura 2-loaded MC3T3-E1 cells. Pretreatment with 1,25(OH)2D3 concentrations, which alone did not produce Ca2+ transients, consistently enhanced Ca2+ responses to PTH. Enhancement was dose dependent over the range of 1 to 10 nM and was blocked by pretreatment with 5 microM nitrendipine during pretreatment. A 1,25(OH)2D3 analog that activates L-type channels and shifts their activation threshold also enhanced PTH responses. In contrast, an analog devoid of membrane Ca2+ effects did not enhance PTH-induced Ca2+ transients. The PTH-induced Ca2+ transient involved activation of a dihydropyridine-insensitive cation channel that was inhibited by Gd3+. Together, these data suggest that 1,25(OH)2D3 increases osteoblast responsiveness to PTH through rapid modification of L-type Ca2+ channel gating properties, whose activation enhances Ca2+ entry through other channels such as the PTH-responsive, Gd(3+)-sensitive cation channel.

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

    PubMed Central

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

    2007-01-01

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

  8. Differences in mineral metabolism among nonhuman primates receiving diets with only vitamin D3 or only vitamin D2.

    PubMed

    Marx, S J; Jones, G; Weinstein, R S; Chrousos, G P; Renquist, D M

    1989-12-01

    We tested for differences in aspects of mineral metabolism during the administration of diets with only vitamin D3 or only vitamin D2 in four nonhuman anthropoid primate species [two catarrhini, Macaca fascicularis (crab-eating macaque) and Macaca mulatta (rhesus macaque), and two platyrrhini, Saimiri sciureus (squirrel monkey) and Aotus vociferans (night monkey)]. All four species maintained approximately 2- to 3-fold higher serum 25-hydroxyvitamin D (25OHD) level while receiving vitamin D3 than while receiving similar amounts of vitamin D2. Serum 25OHD in M. mulatta receiving the standard primate dietary supplement of vitamin D3 was high enough (360 +/- 60 vs. 70 +/- 25 nM in vitamin D-supplemented humans; P less than 0.0001) to suggest that this widely used level of vitamin D3 supplementation is excessive for some M. mulatta. Serum 24,25-dihydroxyvitamin D [24,25-(OH)2D] in A. vociferans was uniquely high [P less than 0.01; species mean, 19 +/- 5, 95 +/- 12, and 27 +/- 5 nM in groups receiving diets with 1.5 IU vitamin D3/g, 6.6 IU vitamin D3/g, and 15 IU vitamin D2/g, respectively; mean 24,25-(OH)2D from the other three species pooled across three diets was 7 +/- 5 nM]. We confirmed relative resistance to 1,25-(OH)2D in S. sciureus, manifested by osteomalacia and moderately high serum 1,25-(OH)2D. Serum 1,25-(OH)2D in S. sciureus increased 4-fold (P less than 0.05) when the precursor in serum was changed from 250HD3 to 250HD2, suggesting that this species shows more severe resistance to 1,25-(OH)2D2 than to 1,25-(OH)2D3. In conclusion, we found many differences in vitamin D metabolism among four nonhuman anthropoid primate species. The striking feature in A. vociferans (high, 24,25-(OH)2D without high 25OHD in serum independent of whether diet contained only vitamin D3 or only vitamin D2) should allow determination of whether 24,25-(OH)2D functions as a unique agonist or an inactive metabolite in this species.

  9. Modulation of peritoneal macrophage antimicrobial activity by peritoneal dialysis fluid, Ca++, and 1,25(OH)2D3 in CAPD patients.

    PubMed

    Carozzi, S; Nasini, M G; Schelotto, C; Caviglia, P M; Barocci, S; Cantaluppi, A; Salit, M

    1990-01-01

    Previous in vitro studies showed that Ca++ and 1,25(OH)2D3 modulate peritoneal macrophage (PM0) antimicrobial activity in CAPD patients. Twenty-four CAPD patients were evaluated in vivo (12 who had never had peritonitis, and 12 with an overall peritonitis incidence of more than one episode per 8 patient/months), for the effects of different peritoneal dialysis fluids (PDF) and Ca++ concentrations (1.25, 1.75, and 2.25 mmol/L) on PM0: cytoplasmic Ca++ concentration; superoxide generation; leukotriene B4 (LTB4) release; and bacterial killing for Staphylococcus epidermidis. The same parameters were also evaluated after adding 1,25(OH)2D3 (0.25 microgram/L) to the PDF. Results showed a direct correlation between the PDF Ca++ concentration and PM0 Ca++ levels, superoxide and LTB4 generation, and bacterial killing such that, with 2.25 mmol/L of Ca++, these values were significantly higher than those seen with 1.75 mmol/L. The addition of 1,25(OH)2D3 potentiated the Ca(++)-induced effects. On the other hand, with PDF Ca++ levels of 1,25 mmol/L, an inhibition of the aforementioned parameters was seen. However, this effect was reversed by the addition of 1,25(OH)2D3. These in vivo results confirm the importance of Ca++ and 1,25(OH)2D3 in PM0 antibacterial function in CAPD patients, and may be useful in determining the prophylaxis and therapy of peritonitis.

  10. 1,25(OH)2D3 Promotes the Efficacy of CD28 Costimulation Blockade by Abatacept

    PubMed Central

    Gardner, David H.; Jeffery, Louisa E.; Soskic, Blagoje; Briggs, Zoe; Hou, Tie Zheng; Raza, Karim

    2015-01-01

    Inhibition of the CD28:CD80/CD86 T cell costimulatory pathway has emerged as an effective strategy for the treatment of T cell–mediated inflammatory diseases. However, patient responses to CD28-ligand blockade by abatacept (CTLA-4-Ig) in conditions such as rheumatoid arthritis are variable and often suboptimal. In this study, we show that the extent to which abatacept suppresses T cell activation is influenced by the strength of TCR stimulation, with high-strength TCR stimulation being associated with relative abatacept insensitivity. Accordingly, cyclosporin A, an inhibitor of T cell stimulation via the TCR, synergized with abatacept to inhibit T cell activation. We also observed that 1,25-dihydroxyvitamin D3 enhanced the inhibition of T cell activation by abatacept, strongly inhibiting T cell activation driven by cross-linked anti-CD3, but with no effect upon anti-CD28 driven stimulation. Thus, like cyclosporin A, 1,25-dihydroxyvitamin D3 inhibits TCR-driven activation, thereby promoting abatacept sensitivity. Vitamin D3 supplementation may therefore be a useful adjunct for the treatment of conditions such as rheumatoid arthritis in combination with abatacept to promote the efficacy of treatment. PMID:26276872

  11. 1,25(OH)2D3 and VDR Signaling Pathways Regulate the Inhibition of Dectin-1 Caused by Cyclosporine A in Response to Aspergillus Fumigatus in Human Corneal Epithelial Cells

    PubMed Central

    Xia, Yiping; Zhao, Guiqiu; Lin, Jing; Li, Cui; Cong, Lin; Jiang, Nan; Xu, Qiang; Wang, Qian

    2016-01-01

    Background The objective of this study is to observe whether cyclosporine A (CsA) inhibits the expression of dectin-1 in human corneal epithelial cells infected with Aspergillus fumigatus (A. fumigatus) and to investigate the molecular mechanisms of the inhibition. Methods Immortalized human corneal epithelial cells (HCECs) were pretreated with 1,25(OH)2D3 and VDR inhibitor for 1 h, and then they were pretreated with CsA for 12h. After these pretreatments, the HCECs were stimulated with A. fumigatus and curdlan respectively, and the expression of dectin-1 and proinflammatory cytokines (IL-1β and TNF-α) were detected by RT-PCR, western blot and ELISA. Results Dectin-1 mRNA and dectin-1 protein expression increased when HCECs were stimulated with A. fumigatus or curdlan, and CsA inhibited the dectin-1 expression both in mRNA and protein levels specifically. Dectin-1 and proinflammatory cytokine expression levels were higher when HCECs were pretreated with VDR inhibitor and CsA compared to pretreatment with CsA alone, while dectin-1 and proinflammatory cytokine levels were lower when HCECs were pretreated with 1,25(OH)2D3 and CsA compared to pretreatment with CsA alone. Conclusions These data provide evidence that CsA can inhibit the expression of dectin-1 and proinflammatory cytokines through dectin-1 when HCECs are stimulated by A. fumigatus or curdlan. The active form of vitamin D, 1,25(OH)2D3, and VDR signaling pathway regulate the inhibition of CsA. The inhibition is enhanced by 1,25(OH)2D3, and the VDR inhibitor suppresses the inhibition. PMID:27755569

  12. Suntanning and cutaneous synthesis of vitamin D3.

    PubMed

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

    1990-07-01

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

  13. The Kinetics of Vitamin D3 in the Osteoblastic Cell

    PubMed Central

    Buchanan, James L; Gilbert, Robert; Ou, Yvonne; Nohe, Anja; Schaefer, Rachel

    2014-01-01

    Experimental evidience is presented on the translocation of vitamin D metabolite, 1,25-(OH)2D3, from the membrane to the nucleus in osteoblast progenitor cells. A mathematical model permitting traversal of the cytoplasm at either a fixed velocity or by diffusion is formulated in order to determine whether transport along the cytoskeletal tracks is more consistent with the observed spatial-temporal distribution than diffusion, and it is so found. The model includes reactions in the nucleus involving D3 to form other compounds, such as protegerin, and thus also makes predictions of the concentrations of these compounds in various regions of the cell. PMID:23775045

  14. Performance Evaluation of Siemens ADVIA Centaur and Roche MODULAR Analytics E170 Total 25-OH Vitamin D Assays

    PubMed Central

    Chen, Yu; Kinney, Lois; Božović, Andrea; Smith, Hilary; Tarr, Heather; Diamandis, Eleftherios P.; LeBlanc, Adrien

    2014-01-01

    Objectives To evaluate the newly developed Roche MODULAR Analytics E170 Total Vitamin D and the Siemens ADVIA Centaur® Vitamin D Total assays. Materials and Methods Assays were evaluated using the Clinical and Laboratory Standards Institute protocols. Split patient samples were compared with LC-MS/MS and DiaSorin LIAISON assays (n=79 including 15 specimens with detectable endogenous 25-OH vitamin D2). Assay accuracy was also evaluated using the Vitamin D External Quality Assessment Scheme samples. Results The ADVIA Centaur and E170 assays demonstrated maximum total CVs of 14.1% and 5.9%, respectively. Both showed excellent linearity (R2 >0.99). The ADVIA Centaur assay demonstrated interference with bilirubin at 800 μmol/L, hemolysis at 1.25 g/L, and triglycerides at 2.8 mmol/L. Compared to LC-MS/MS, the ADVIA Centaur assay demonstrated a R2 value of 0.893, average bias of −8.8%; the E170 assay an R2 value of 0.872, average bias of 14.3% with underestimation of 25-OH vitamin D2. Compared to the LIAISON assay, the ADVIA Centaur assay demonstrated an R2 value of 0.781, average bias of −17.3%; the E170 assay an R2 value of 0.823, average bias of 11.4%. The ADVIA Centaur and E170 assays demonstrated a biases of <20% in 10/10 and 8/10 samples, respectively. Conclusions The ADVIA Centaur and E170 vitamin D assays demonstrated acceptable linearity, imprecision, and accuracy. The E170 assay demonstrated consistent underestimation of 25-OH vitamin D2 levels. Compared with LC-MS/MS, the ADVIA Centaur assay demonstrated a higher R2 value and a smaller average bias than the E170 assay. PMID:22705028

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

    PubMed Central

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

    1998-01-01

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

  16. Hepcidin and 1,25(OH)2D3 effectively restore Ca2+ transport in β-thalassemic mice: reciprocal phenomenon of Fe2+ and Ca2+ absorption.

    PubMed

    Kraidith, Kamonshanok; Svasti, Saovaros; Teerapornpuntakit, Jarinthorn; Vadolas, Jim; Chaimana, Rattana; Lapmanee, Sarawut; Suntornsaratoon, Panan; Krishnamra, Nateetip; Fucharoen, Suthat; Charoenphandhu, Narattaphol

    2016-07-01

    Previously, β-thalassemia, an inherited anemic disorder with iron overload caused by loss-of-function mutation of β-globin gene, has been reported to induce osteopenia and impaired whole body calcium metabolism, but the pathogenesis of aberrant calcium homeostasis remains elusive. Herein, we investigated how β-thalassemia impaired intestinal calcium absorption and whether it could be restored by administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or hepcidin, the latter of which was the liver-derived antagonist of intestinal iron absorption. The results showed that, in hemizygous β-globin knockout (BKO) mice, the duodenal calcium transport was lower than that in wild-type littermates, and severity was especially pronounced in female mice. Both active and passive duodenal calcium fluxes in BKO mice were found to be less than those in normal mice. This impaired calcium transport could be restored by 7-day 1,25(OH)2D3 treatment. The 1,25(OH)2D3-induced calcium transport was diminished by inhibitors of calcium transporters, e.g., L-type calcium channel, NCX1, and PMCA1b, as well as vesicular transport inhibitors. Interestingly, the duodenal calcium transport exhibited an inverse correlation with transepithelial iron transport, which was markedly enhanced in thalassemic mice. Thus, 3-day subcutaneous hepcidin injection and acute direct hepcidin exposure in the Ussing chamber were capable of restoring the thalassemia-associated impairment of calcium transport; however, the positive effect of hepcidin on calcium transport was completely blocked by proteasome inhibitors MG132 and bortezomib. In conclusion, both 1,25(OH)2D3 and hepcidin could be used to alleviate the β-thalassemia-associated impairment of calcium absorption. Therefore, our study has shed light on the development of a treatment strategy to rescue calcium dysregulation in β-thalassemia. PMID:27245334

  17. Vitamin D3: a helpful immuno-modulator

    PubMed Central

    Di Rosa, Michelino; Malaguarnera, Michele; Nicoletti, Ferdinando; Malaguarnera, Lucia

    2011-01-01

    The active metabolite of vitamin D, 1α, 25-dihydroxyvitamin D3 [1,25(OH)2D3], is involved in calcium and phosphate metabolism and exerts a large number of biological effects. Vitamin D3 inhibits parathyroid hormone secretion, adaptive immunity and cell proliferation, and at the same time promotes insulin secretion, innate immunity and stimulates cellular differentiation. The role of vitamin D3 in immunoregulation has led to the concept of a dual function as both as an important secosteroid hormone for the regulation of body calcium homeostasis and as an essential organic compound that has been shown to have a crucial effect on the immune responses. Altered levels of vitamin D3 have been associated, by recent observational studies, with a higher susceptibility of immune-mediated disorders and inflammatory diseases. This review reports the new developments with specific reference to the metabolic and signalling mechanisms associated with the complex immune-regulatory effects of vitamin D3 on immune cells. PMID:21896008

  18. Interlaboratory trial for measurement of vitamin D and 25(OH)D in foods and a dietary supplement using liquid chromatography-mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Assessment of total vitamin D intake from foods and dietary supplements (DSs) may be incomplete if 25-hydroxyvitamin D [25(OH)D] intake is not included. However, 25(OH)D data for such intake assessments are lacking, no food or DS reference materials (RMs) are available, and comparison of laboratory...

  19. 1,25(OH)2D3-enhanced hypercalciuria in genetic hypercalciuric stone-forming rats fed a low-calcium diet

    PubMed Central

    Asplin, John R.; Krieger, Nancy S.; Culbertson, Christopher D.; Asplin, Daniel M.; Bushinsky, David A.

    2013-01-01

    The inbred genetic hypercalciuric stone-forming (GHS) rats exhibit many features of human idiopathic hypercalciuria and have elevated levels of vitamin D receptors (VDR) in calcium (Ca)-transporting organs. On a normal-Ca diet, 1,25(OH)2D3 (1,25D) increases urine (U) Ca to a greater extent in GHS than in controls [Sprague-Dawley (SD)]. The additional UCa may result from an increase in intestinal Ca absorption and/or bone resorption. To determine the source, we asked whether 1,25D would increase UCa in GHS fed a low-Ca (0.02%) diet (LCD). With 1,25D, UCa in SD increased from 1.2 ± 0.1 to 9.3 ± 0.9 mg/day and increased more in GHS from 4.7 ± 0.3 to 21.5 ± 0.9 mg/day (P < 0.001). In GHS rats on LCD with or without 1,25D, UCa far exceeded daily Ca intake (2.6 mg/day). While the greater excess in UCa in GHS rats must be derived from bone mineral, there may also be a 1,25D-mediated decrease in renal tubular Ca reabsorption. RNA expression of the components of renal Ca transport indicated that 1,25D administration results in a suppression of klotho, an activator of the renal Ca reabsorption channel TRPV5, in both SD and GHS rats. This fall in klotho would decrease tubular reabsorption of the 1,25D-induced bone Ca release. Thus, the greater increase in UCa with 1,25D in GHS fed LCD strongly suggests that the additional UCa results from an increase in bone resorption, likely due to the increased number of VDR in the GHS rat bone cells, with a possible component of decreased renal tubular calcium reabsorption. PMID:23926184

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

    PubMed

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

    2014-02-01

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

  1. Kidney-specific upregulation of vitamin D3 target genes in ClC-5 KO mice.

    PubMed

    Maritzen, T; Rickheit, G; Schmitt, A; Jentsch, T J

    2006-07-01

    Mutations in ClC-5 cause Dent's disease, a disorder associated with low molecular weight proteinuria, hyperphosphaturia, and kidney stones. ClC-5 is a Cl(-)/H(+)-exchanger predominantly expressed in the kidney, where it facilitates the acidification of proximal tubular endosomes. The reduction in proximal tubular endocytosis resulting from a lack of ClC-5 raises the luminal concentration of filtered proteins and peptides like parathyroid hormone (PTH). The increase in PTH may explain the hyperphosphaturia observed in Dent's disease. Expression profiling, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and hormone measurements were used to investigate whether the disruption of ClC-5 affects other signalling pathways. Although the upregulation of 25(OH)(2)-vitamin D(3) 1alpha-hydroxylase and downregulation of vitamin D(3) 24-hydroxylase suggested an increased formation of 1,25(OH)(2)-vitamin D(3), the concentration of this active metabolite was reduced in the serum of ClC-5 knockout (KO) mice. However, target genes of 1,25(OH)(2)-vitamin D(3) were upregulated in KO kidneys. Expression analysis of intestine and bone revealed that the upregulation of 1,25(OH)(2)-vitamin D(3) target genes was kidney intrinsic and not systemic. In spite of reduced serum levels of 1,25(OH)(2)-vitamin D(3) in ClC-5 KO mice, 1,25(OH)(2)-vitamin D(3) is increased in later nephron segments as a consequence of impaired proximal tubular endocytosis. This leads to a kidney-specific stimulation of 1,25(OH)(2)-vitamin D(3) target genes that may contribute to the pathogenesis of Dent's disease. The activation of genes in distal nephron segments by hormones that are normally endocytosed in the proximal tubule may extend to other pathways like those activated by retinoic acid.

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

    PubMed

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

    2010-10-01

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

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

    PubMed

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

    2013-07-01

    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 dragons fed a diet low in vitamin D can use stored vitamin D and its metabolites to maintain plasma 25(OH)D(3) and 1,25(OH)(2)D(3) concentrations after discontinuing UVb exposure. Blood samples of healthy adult female bearded dragons, exposed to UVb radiation for over 6 months were collected (day 0) after which UVb exposure was discontinued for 83 days and blood was collected. Blood plasma was analysed for concentrations of total Ca, total P, ionized Ca, uric acid, 25(OH)D(3) and 1,25(OH)(2)D(3). There was no significant change in plasma 25(OH)D(3) and 1,25(OH)(2)D(3) concentrations during the study. While total Ca and P in whole blood was found to significantly decrease over time (P < 0.0088 and 0.0016, respectively), values were within the reference range. Plasma ionized Ca tended (P = 0.0525) to decrease during the study. Adult female bearded dragons, previously exposed to UVb, are able to maintain blood vitamin D metabolite concentrations when UVb exposure is discontinued for a period of up to 83 days. PMID:23648288

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

    PubMed

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

    2013-07-01

    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 dragons fed a diet low in vitamin D can use stored vitamin D and its metabolites to maintain plasma 25(OH)D(3) and 1,25(OH)(2)D(3) concentrations after discontinuing UVb exposure. Blood samples of healthy adult female bearded dragons, exposed to UVb radiation for over 6 months were collected (day 0) after which UVb exposure was discontinued for 83 days and blood was collected. Blood plasma was analysed for concentrations of total Ca, total P, ionized Ca, uric acid, 25(OH)D(3) and 1,25(OH)(2)D(3). There was no significant change in plasma 25(OH)D(3) and 1,25(OH)(2)D(3) concentrations during the study. While total Ca and P in whole blood was found to significantly decrease over time (P < 0.0088 and 0.0016, respectively), values were within the reference range. Plasma ionized Ca tended (P = 0.0525) to decrease during the study. Adult female bearded dragons, previously exposed to UVb, are able to maintain blood vitamin D metabolite concentrations when UVb exposure is discontinued for a period of up to 83 days.

  5. 1,25(OH)2D3 attenuates TGF-β1/β2-induced increased migration and invasion via inhibiting epithelial-mesenchymal transition in colon cancer cells.

    PubMed

    Chen, Shanwen; Zhu, Jing; Zuo, Shuai; Ma, Ju; Zhang, Junling; Chen, Guowei; Wang, Xin; Pan, Yisheng; Liu, Yucun; Wang, Pengyuan

    1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been reported to inhibit proliferation and migration of multiple types of cancer cells. However, the mechanism underlying its anti-metastasis effect is not fully illustrated. In this study, the effect of 1,25(OH)2D3 on TGF-β1/β2-induced epithelial-mesenchymal transition (EMT) is tested in colon cancer cells. The results suggest that 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased invasion and migration of in SW-480 and HT-29 cells. 1,25(OH)2D3 also inhibited the cadherin switch in SW-480 and HT-29 cells. TGF-β1/β2-induced increased expression of EMT-related transcription factors was also inhibited by 1,25(OH)2D3. 1,25(OH)2D3 also inhibited the secretion of MMP-2 and MMP-9 and increased expression of F-actin induced by TGF-β1/β2 in SW-480 cells. Taken together, this study suggests that the suppression of EMT might be one of the mechanisms underlying the anti-metastasis effect of 1,25(OH)2D3 in colon cancer cells.

  6. 25 (OH) Vitamin D Levels and Renal Disease Progression in Patients with Type 2 Diabetic Nephropathy and Blockade of the Renin-Angiotensin System

    PubMed Central

    Luño, José; Barrio, Vicente; de Vinuesa, Soledad García; Praga, Manuel; Goicoechea, Marian; Lahera, Vicente; Casas, Luisa; Oliva, Jesús

    2013-01-01

    Summary Background and objectives Experimental studies show that 25 (OH) vitamin D is a suppressor of renin biosynthesis and that vitamin D deficiency has been associated with CKD progression. Patients with type II diabetes and CKD have an exceptionally high rate of severe 25 (OH) vitamin D deficiency; however, it is not known whether this deficiency is a risk factor for progression of diabetic nephropathy. This study aimed to investigate whether there is an association of 25 (OH) vitamin D deficiency with disease progression in type II diabetic nephropathy. Design, setting, participants, & measurements 25 (OH) vitamin D levels were measured at baseline and 4 and 12 months in 103 patients included in a multicenter randomized controlled trial to compare the efficacy of combining an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker with the efficacy of each drug in monotherapy to slow progression of established diabetic nephropathy during 2006–2011. The primary composite endpoint was a >50% increase in baseline serum creatinine, ESRD, or death. All study participants were included in the analysis. Results Fifty-three patients (51.5%) had 25 (OH) vitamin D deficiency (<15 ng/ml). After a median follow-up of 32 months, the endpoint was reached by 23 patients with deficiency (43.4%) and 8 patients without (16%). Multivariate Cox regression analysis adjusted for urinary protein/creatinine ratio, estimated GFR, and baseline aldosterone showed that 25 (OH) vitamin D deficiency was associated with the primary endpoint (hazard ratio, 2.88; 95% confidence interval, 1.84 to 7.67; P=0.04). Conclusions These results show that 25 (OH) vitamin D deficiency is independently associated with a higher risk of the composite outcome in patients with type II diabetic nephropathy. PMID:24135218

  7. Mechanical loading and the synthesis of 1,25(OH)2D in primary human osteoblasts.

    PubMed

    van der Meijden, K; Bakker, A D; van Essen, H W; Heijboer, A C; Schulten, E A J M; Lips, P; Bravenboer, N

    2016-02-01

    local vitamin D metabolism in primary human osteoblasts. Our results suggest that 1,25(OH)2D3 and mechanical loading, both stimuli of the differentiation of osteoblasts, interact at the cellular level.

  8. A Population-Based Model to Consider the Effect of Seasonal Variation on Serum 25(OH)D and Vitamin D Status

    PubMed Central

    Vuistiner, Philippe; Rousson, Valentin; Henry, Hugues; Lescuyer, Pierre; Boulat, Olivier; Gaspoz, Jean-Michel; Mooser, Vincent; Vollenweider, Peter; Waeber, Gerard; Cornuz, Jacques; Paccaud, Fred; Bochud, Murielle; Guessous, Idris

    2015-01-01

    Background. We elaborated a model that predicts the centiles of the 25(OH)D distribution taking into account seasonal variation. Methods. Data from two Swiss population-based studies were used to generate (CoLaus) and validate (Bus Santé) the model. Serum 25(OH)D was measured by ultra high pressure LC-MS/MS and immunoassay. Linear regression models on square-root transformed 25(OH)D values were used to predict centiles of the 25(OH)D distribution. Distribution functions of the observations from the replication set predicted with the model were inspected to assess replication. Results. Overall, 4,912 and 2,537 Caucasians were included in original and replication sets, respectively. Mean (SD) 25(OH)D, age, BMI, and % of men were 47.5 (22.1) nmol/L, 49.8 (8.5) years, 25.6 (4.1) kg/m2, and 49.3% in the original study. The best model included gender, BMI, and sin-cos functions of measurement day. Sex- and BMI-specific 25(OH)D centile curves as a function of measurement date were generated. The model estimates any centile of the 25(OH)D distribution for given values of sex, BMI, and date and the quantile corresponding to a 25(OH)D measurement. Conclusions. We generated and validated centile curves of 25(OH)D in the general adult Caucasian population. These curves can help rank vitamin D centile independently of when 25(OH)D is measured. PMID:26421279

  9. Impact of Vitamin D3 Dietary Supplement Matrix on Clinical Response

    PubMed Central

    Finnell, John S.; Bhandiwad, Anup; Oberg, Erica; Suhaila, Lena; Bradley, Ryan

    2014-01-01

    Context: As a result of research suggesting increased health risk with low serum 25-hydroxycholecalciferol (25(OH)D), health care providers are measuring it frequently. Providers and patients are faced with treatment choices when low status is identified. Objective: To compare the safety and efficacy of three vitamin D3 dietary supplements with different delivery matrices. Setting and Design: A 12-week, parallel group, single-masked, clinical trial was conducted in Seattle, Washington and Kailua Kona, Hawaii. Sixty-six healthy adults with (25(OH)D) <33 ng/mL were randomly assigned to take one of three D3 supplements, ie, a chewable tablet (TAB), an oil-emulsified drop (DROP), or an encapsulated powder (CAP) at a label-claimed dose of 10,000 IU/day. Actual D3 content was assessed by a third party and the results adjusted based on the actual D3 content administered. Mean change in 25(OH)D/mcg D3 administered; difference in the proportion of D3 insufficient participants (ie, 25(OH)D ≤30 ng/mL) reaching sufficiency (ie, 25(OH)D ≥30 ng/mL); and mean change in serum 1, 25-dihydroxycholecalciferol were measured. Results: In two of the three products tested, the measured vitamin D3 content varied considerably from the label-claimed dose. Differences in 25(OH)D/mcg D3 administered were significantly different between groups (P = .04; n = 55). Pairwise comparisons demonstrated DROP resulted in a greater increase than TAB (P < .05) but not than CAP. TAB was not different from CAP. The proportions reaching sufficiency were: 100% (TAB and CAP) and 80% (DROP) (P = .03 between groups; n = 55). 1, 25-Dihydroxycholecalciferol did not change significantly in any group. Conclusions: Oil-emulsified vitamin D3 supplements resulted in a greater mean change in serum 25(OH)D concentration, but fewer patients reaching vitamin D sufficiency, than chewable or encapsulated supplements. PMID:24684456

  10. Vitamin D3 Inhibits Hedgehog Signaling and Proliferation in Murine Basal Cell Carcinomas

    PubMed Central

    Tang, Jean Y.; Xiao, Tony Zheng; Oda, Yuko; Chang, Kris S.; Shpall, Elana; Wu, Angela; So, Po-Lin; Hebert, Jennifer; Bikle, Daniel; Epstein, Ervin H.

    2011-01-01

    Constitutive Hedgehog (HH) signaling underlies several human tumors, including basal cell carcinoma (BCC). Recently, Bijlsma et al (Bijlsma MF, et al. (2006) PLoS Biol 4: 1397–1410) reported a new biologic function for vitamin D3 in suppressing HH signaling in an in vitro model system. Based on that work, we have assessed effects of vitamin D3 on HH signaling and proliferation of murine BCCs in vitro and in vivo. We find that indeed in BCC cells, vitamin D3 blocks both proliferation and HH signaling as assessed by mRNA expression of the HH target gene Gli1. These effects of vitamin D3 on Gli1 expression and on BCC cell proliferation are comparable to the effects of cyclopamine, a known inhibitor of the HH pathway. These results are specific for vitamin D3, since the precursor 7-dehydrocholesterol and the downstream products 25-hydroxy vitamin D3 [25(OH)D] and 1,25-dihydroxy vitamin D3 [1,25(OH)2D] are considerably less effective in reducing either Gli1 mRNA or cellular proliferation. Moreover, these effects seem to be independent of the vitamin D receptor (VDR) since shRNA knock down of VDR does not abrogate the anti HH effects of D3 despite reducing expression of the VDR target gene 24-hydroxylase. Finally, topical vitamin D3 treatment of existing murine BCC tumors significantly decreases Gli1 and Ki67 staining. Thus, topical vitamin D3 acting via its HH inhibiting effect may hold promise as an effective anti-BCC agent. PMID:21436386

  11. Determination of optimal vitamin D3 dosing regimens in HIV-infected paediatric patients using a population pharmacokinetic approach

    PubMed Central

    Foissac, Frantz; Meyzer, Candice; Frange, Pierre; Chappuy, Hélène; Benaboud, Sihem; Bouazza, Naïm; Friedlander, Gérard; Souberbielle, Jean-Claude; Urien, Saïk; Blanche, Stéphane; Tréluyer, Jean-Marc

    2014-01-01

    Aims To investigate 25-hydroxycholecalciferol [25(OH)D] population pharmacokinetics in children and adolescents, to establish factors that influence 25(OH)D pharmacokinetics and to assess different vitamin D3 dosing schemes to reach sufficient 25(OH)D concentrations (>30 ng ml−1). Methods This monocentric prospective study included 91 young HIV-infected patients aged 3 to 24 years. Patients received a 100 000 IU vitamin D3 supplementation. A total of 171 25(OH)D concentrations were used to perform a population pharmacokinetic analysis. Results At baseline 28% of patients had 25(OH)D concentrations below 10 ng ml−1, 69% between 10 and 30 ng ml−1 and 3% above 30 ng ml−1. 25(OH)D pharmacokinetics were best described by a one compartment model with an additional production parameter reflecting the input from diet and sun exposure. The effects of skin phototype and bodyweight were significant on 25(OH)D production before any supplementation. The basal level was 27% lower in non-white skin phototype patients and was slightly decreased with bodyweight. No significant differences in 25(OH)D concentrations were related to antiretroviral drugs. To obtain concentrations between 30 and 80 ng ml−1, patients with baseline concentrations between 10 and 30 ng ml−1 should receive 100 000 IU per 3 months. However, vitamin D deficient patients (<10 ng ml−1) would need an intensive phase of 100 000 IU per 2 weeks (two times) followed 2 weeks later by a maintenance phase of 100 000 IU per 3 months. Conclusions Skin phototype and bodyweight had an influence on the basal production of 25(OH)D. According to 25(OH)D baseline concentrations, dosing schemes to reach sufficient concentrations are proposed. PMID:24902982

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

    PubMed

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

    2016-04-14

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

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

    PubMed

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

    2016-04-14

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

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

    PubMed

    Russell, Meghan

    2012-09-01

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

  15. Vitamin D3 and brain development.

    PubMed

    Eyles, D; Brown, J; Mackay-Sim, A; McGrath, J; Feron, F

    2003-01-01

    Evidence for the presence of the vitamin D receptor in brain implies this vitamin may have some function in this organ. This study investigates whether vitamin D(3) acts during brain development. We demonstrate that rats born to vitamin D(3)-deficient mothers had profound alterations in the brain at birth. The cortex was longer but not wider, the lateral ventricles were enlarged, the cortex was proportionally thinner and there was more cell proliferation throughout the brain. There were reductions in brain content of nerve growth factor and glial cell line-derived neurotrophic factor and reduced expression of p75(NTR), the low-affinity neurotrophin receptor. Our findings would suggest that low maternal vitamin D(3) has important ramifications for the developing brain. PMID:12710973

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

    PubMed Central

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

    2014-01-01

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

  17. Strong association between non alcoholic fatty liver disease (NAFLD) and low 25(OH) vitamin D levels in an adult population with normal serum liver enzymes

    PubMed Central

    2011-01-01

    Background Hypovitaminosis D has been recently recognized as a worldwide epidemic. Since vitamin D exerts significant metabolic activities, comprising free fatty acids (FFA) flux regulation from the periphery to the liver, its deficiency may promote fat deposition into the hepatocytes. Aim of our study was to test the hypothesis of a direct association between hypovitaminosis D and the presence of NAFLD in subjects with various degree of insulin-resistance and related metabolic disorders. Methods We studied 262 consecutive subjects referred to the Diabetes and Metabolic Diseases clinics for metabolic evaluation. NAFLD (non-alcoholic fatty liver disease) was diagnosed by upper abdomen ultrasonography, metabolic syndrome was identified according to the Third Report of National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATPIII) modified criteria. Insulin-resistance was evaluated by means of HOMA-IR. Fatty-Liver-Index, a recently identified correlate of NAFLD, was also estimated. Serum 25(OH)vitamin D was measured by colorimetric method. Results Patients with NAFLD (n = 162,61.8%) had reduced serum 25(OH) vitamin D levels compared to subjects without NAFLD (14.8 ± 9.2 vs 20.5 ± 9.7 ng/ml, p < 0.001, OR 0.95, IC 95% 0.92-0.98). The relationship between NAFLD and reduced 25(OH)vitamin D levels was independent from age, sex, triglycerides, high density lipoproteins (HDL) and glycaemia (p < 0.005) and Fatty Liver Index inversely correlated with low 25(OH) vitamin D regardless sex, age and HOMA-IR (p < 0.007). Conclusions Low 25(OH)vitamin D levels are associated with the presence of NAFLD independently from metabolic syndrome, diabetes and insulin-resistance profile. PMID:21749681

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

    SciTech Connect

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

    1986-08-26

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

  19. Human Pigmentation, Cutaneous Vitamin D Synthesis and Evolution: Variants of Genes (SNPs) Involved in Skin Pigmentation Are Associated with 25(OH)D Serum Concentration.

    PubMed

    Rossberg, Willi; Saternus, Roman; Wagenpfeil, Stefan; Kleber, Marcus; März, Winfried; Reichrath, Sandra; Vogt, Thomas; Reichrath, Jörg

    2016-03-01

    Vitamin D deficiency is common and associated with higher risk for and unfavourable outcome of many diseases. Limited data exist on genetic determinants of serum 25(OH)D concentration. In a cohort of the LURIC study (n=2974, median 25(OH)D concentration 15.5 ng/ml), we tested the hypothesis that variants (SNPs, n=244) of several genes (n=15) involved in different aspects of skin pigmentation, including melanosomal biogenesis (ATP7A, DTNBP1, BLOC1S5, PLDN, PMEL), melanosomal transport within melanocytes (RAB27A, MYO5A, MLPH); or various melanocyte signaling pathways (MC1R, MITF, PAX3, SOX10, DKK1, RACK1, CNR1) are predictive of serum 25(OH)D levels. Eleven SNPs located in 6 genes were associated (p<0.05) with low or high serum 25(OH)D levels, 3 out of these 11 SNPs reached the aimed significance level after correction for multiple comparisons (FDR). In the linear regression model adjusted for sex, body mass index (BMI), year of birth and month of blood sample rs7565264 (MLPH), rs10932949 (PAX3), and rs9328451 (BLOC1S5) showed a significant association with 25(OH)D. The combined impact on variation of 25(OH)D serum levels (coefficient of determination (R(2))) for the 11 SNPs was 1.6% and for the 3 SNPs after FDR 0.3%. In Cox Regression we identified rs2292881 (MLPH) as having a significant association (advantage) with overall survival. Kaplan-Meier analysis did not show any significant impact of individual SNPs on overall survival. In conclusion, these results shed new light on the role of sunlight, skin pigmentation and vitamin D for human evolution. PMID:26977047

  20. Human Pigmentation, Cutaneous Vitamin D Synthesis and Evolution: Variants of Genes (SNPs) Involved in Skin Pigmentation Are Associated with 25(OH)D Serum Concentration.

    PubMed

    Rossberg, Willi; Saternus, Roman; Wagenpfeil, Stefan; Kleber, Marcus; März, Winfried; Reichrath, Sandra; Vogt, Thomas; Reichrath, Jörg

    2016-03-01

    Vitamin D deficiency is common and associated with higher risk for and unfavourable outcome of many diseases. Limited data exist on genetic determinants of serum 25(OH)D concentration. In a cohort of the LURIC study (n=2974, median 25(OH)D concentration 15.5 ng/ml), we tested the hypothesis that variants (SNPs, n=244) of several genes (n=15) involved in different aspects of skin pigmentation, including melanosomal biogenesis (ATP7A, DTNBP1, BLOC1S5, PLDN, PMEL), melanosomal transport within melanocytes (RAB27A, MYO5A, MLPH); or various melanocyte signaling pathways (MC1R, MITF, PAX3, SOX10, DKK1, RACK1, CNR1) are predictive of serum 25(OH)D levels. Eleven SNPs located in 6 genes were associated (p<0.05) with low or high serum 25(OH)D levels, 3 out of these 11 SNPs reached the aimed significance level after correction for multiple comparisons (FDR). In the linear regression model adjusted for sex, body mass index (BMI), year of birth and month of blood sample rs7565264 (MLPH), rs10932949 (PAX3), and rs9328451 (BLOC1S5) showed a significant association with 25(OH)D. The combined impact on variation of 25(OH)D serum levels (coefficient of determination (R(2))) for the 11 SNPs was 1.6% and for the 3 SNPs after FDR 0.3%. In Cox Regression we identified rs2292881 (MLPH) as having a significant association (advantage) with overall survival. Kaplan-Meier analysis did not show any significant impact of individual SNPs on overall survival. In conclusion, these results shed new light on the role of sunlight, skin pigmentation and vitamin D for human evolution.

  1. Gene Expression Profiles in Human and Mouse Primary Cells Provide New Insights into the Differential Actions of Vitamin D3 Metabolites

    PubMed Central

    Tuohimaa, Pentti; Wang, Jing-Huan; Khan, Sofia; Kuuslahti, Marianne; Qian, Kui; Manninen, Tommi; Auvinen, Petri; Vihinen, Mauno; Lou, Yan-Ru

    2013-01-01

    1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) had earlier been regarded as the only active hormone. The newly identified actions of 25-hydroxyvitamin D3 (25(OH)D3) and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) broadened the vitamin D3 endocrine system, however, the current data are fragmented and a systematic understanding is lacking. Here we performed the first systematic study of global gene expression to clarify their similarities and differences. Three metabolites at physiologically comparable levels were utilized to treat human and mouse fibroblasts prior to DNA microarray analyses. Human primary prostate stromal P29SN cells (hP29SN), which convert 25(OH)D3 into 1α,25(OH)2D3 by 1α-hydroxylase (encoded by the gene CYP27B1), displayed regulation of 164, 171, and 175 genes by treatment with 1α,25(OH)2D3, 25(OH)D3, and 24R,25(OH)2D3, respectively. Mouse primary Cyp27b1 knockout fibroblasts (mCyp27b1−/−), which lack 1α-hydroxylation, displayed regulation of 619, 469, and 66 genes using the same respective treatments. The number of shared genes regulated by two metabolites is much lower in hP29SN than in mCyp27b1−/−. By using DAVID Functional Annotation Bioinformatics Microarray Analysis tools and Ingenuity Pathways Analysis, we identified the agonistic regulation of calcium homeostasis and bone remodeling between 1α,25(OH)2D3 and 25(OH)D3 and unique non-classical actions of each metabolite in physiological and pathological processes, including cell cycle, keratinocyte differentiation, amyotrophic lateral sclerosis signaling, gene transcription, immunomodulation, epigenetics, cell differentiation, and membrane protein expression. In conclusion, there are three distinct vitamin D3 hormones with clearly different biological activities. This study presents a new conceptual insight into the vitamin D3 endocrine system, which may guide the strategic use of vitamin D3 in disease prevention and treatment. PMID:24116037

  2. Gestational Vitamin 25(OH)D Status as a Risk Factor for Receptive Language Development: A 24-Month, Longitudinal, Observational Study.

    PubMed

    Tylavsky, Frances A; Kocak, Mehmet; Murphy, Laura E; Graff, J Carolyn; Palmer, Frederick B; Völgyi, Eszter; Diaz-Thomas, Alicia M; Ferry, Robert J

    2015-12-01

    Emerging data suggest that vitamin D status during childhood and adolescence can affect neurocognitive development. The purpose of this study was to investigate whether gestational 25(OH)D status is associated with early childhood cognitive and receptive language development. The Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study (CANDLE) study enrolled 1503 mother-child dyads during the second trimester of healthy singleton pregnancies from Shelby County TN. Among 1020 participants of the total CANDLE cohort for whom 25(OH)D levels were available, mean gestational 25(OH)D level during the second trimester was 22.3 ng/mL (range 5.9-68.4), with 41.7% of values <20 ng/dL. Cognitive and language scaled scores increased in a stair-step manner as gestational 25(OH)D levels in the second trimester rose from <20 ng/dL, through 20-29.99 ng/dL, to ≥30 ng/dL. When controlling for socioeconomic status, race, use of tobacco products, gestational age of the child at birth, and age at the 2-year assessment, the gestational 25(OH)D was positively related to receptive language development (p < 0.017), but not cognitive or expressive language. PMID:26633480

  3. Gestational Vitamin 25(OH)D Status as a Risk Factor for Receptive Language Development: A 24-Month, Longitudinal, Observational Study

    PubMed Central

    Tylavsky, Frances A.; Kocak, Mehmet; Murphy, Laura E.; Graff, J. Carolyn; Palmer, Frederick B.; Völgyi, Eszter; Diaz-Thomas, Alicia M.; Ferry, Robert J.

    2015-01-01

    Emerging data suggest that vitamin D status during childhood and adolescence can affect neurocognitive development. The purpose of this study was to investigate whether gestational 25(OH)D status is associated with early childhood cognitive and receptive language development. The Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study (CANDLE) study enrolled 1503 mother-child dyads during the second trimester of healthy singleton pregnancies from Shelby County TN. Among 1020 participants of the total CANDLE cohort for whom 25(OH)D levels were available, mean gestational 25(OH)D level during the second trimester was 22.3 ng/mL (range 5.9–68.4), with 41.7% of values <20 ng/dL. Cognitive and language scaled scores increased in a stair-step manner as gestational 25(OH)D levels in the second trimester rose from <20 ng/dL, through 20–29.99 ng/dL, to ≥30 ng/dL. When controlling for socioeconomic status, race, use of tobacco products, gestational age of the child at birth, and age at the 2-year assessment, the gestational 25(OH)D was positively related to receptive language development (p < 0.017), but not cognitive or expressive language. PMID:26633480

  4. A Randomized Trial of Vitamin D3 Supplementation in Children: Dose-Response Effects on Vitamin D Metabolites and Calcium Absorption

    PubMed Central

    Laing, E. M.; Hill Gallant, K. M.; Hall, D. B.; McCabe, G. P.; Hausman, D. B.; Martin, B. R.; Warden, S. J.; Peacock, M.; Weaver, C. M.

    2013-01-01

    Context: Changes in serum vitamin D metabolites and calcium absorption with varying doses of oral vitamin D3 in healthy children are unknown. Objective: Our objective was to examine the dose-response effects of supplemental vitamin D3 on serum vitamin D metabolites and calcium absorption in children living at two U.S. latitudes. Design: Black and white children (n = 323) participated in a multisite (U.S. latitudes 34° N and 40° N), triple-masked trial. Children were randomized to receive oral vitamin D3 (0, 400, 1000, 2000, and 4000 IU/d) and were sampled over 12 weeks in winter. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured using RIA and intact PTH (iPTH) by immunoradiometric assay. Fractional calcium absorption was determined from an oral stable isotope 44Ca (5 mg) in a 150-mg calcium meal. Nonlinear and linear regression models were fit for vitamin D metabolites, iPTH, and calcium absorption. Results: The mean baseline 25(OH)D value for the entire sample was 70.0 nmol/L. Increases in 25(OH)D depended on dose with 12-week changes ranging from −10 nmol/L for placebo to 76 nmol/L for 4000 IU. Larger 25(OH)D gains were observed for whites vs blacks at the highest dose (P < .01). Gains for 1,25(OH)2D were not significant (P = .07), and decreases in iPTH were not dose-dependent. There was no dose effect of vitamin D on fractional calcium absorption when adjusted for pill compliance, race, sex, or baseline 25(OH)D. Conclusion: Large increases in serum 25(OH)D with vitamin D3 supplementation did not increase calcium absorption in healthy children living at 2 different latitudes. Supplementation with 400 IU/d was sufficient to maintain wintertime 25(OH)D concentrations in healthy black, but not white, children. PMID:24092833

  5. Vitamin D3 analogs and their 24-oxo metabolites equally inhibit clonal proliferation of a variety of cancer cells but have differing molecular effects.

    PubMed

    Campbell, M J; Reddy, G S; Koeffler, H P

    1997-09-01

    The seco-steroid hormone, 1 alpha, 25 dihydroxyvitamin D3 (1 alpha,25(OH)2D3) binds to a specific nuclear receptor that acts as a ligand-inducible transcription factor. The resulting genomic effects include partial arrest in G0/G1 of the cell cycle and induction of differentiation; these effects have been observed in various types of cancer. Recently, we produced enzymatically the natural 24-oxo metabolites of 1 alpha,25(OH)2D3 and two of its potent synthetic analogs (1 alpha,25-(OH)2-16-ene-D3 and 1 alpha,25-(OH)2-20-epi-D3) using a rat kidney perfusion system. We have found that the 24-oxo metabolites of both 1 alpha,25(OH)2D3 and its analogs have either the same or greater antiproliferative activity against various cancer cells as their parental compounds. Notably, two cell lines (DU-145 (prostate cancer) and MDA-MB-436 [breast cancer]) that were extremely resistant to the antiproliferative effects of vitamin D3 analogs displayed greater sensitivity towards the 24-oxo metabolite of the vitamin D3 analog. Similarly, the 24-oxo metabolites had the capacity to induce differentiation and apoptosis and to diminish the proportion of cells in S phase. Most interestingly, while the analog 1 alpha,25(OH)2-20-epi-D3 induced expression of BRCA1 in MCF-7 breast cancer cells; its 24-oxo metabolite dramatically suppressed BRAC1 expression. Thus, we have shown for the first time that the various biological activities produced by the hormone 1 alpha,25(OH)2D3 and some of its analogs may represent a combination of actions by the hormone 1 alpha,25(OH)2D3 and its natural 24-oxo metabolites.

  6. Role of 1,25-dihydroxyvitamin D3 on intestinal phosphate absorption in rats with a normal vitamin D supply.

    PubMed

    Rizzoli, R; Fleisch, H; Bonjour, J P

    1977-09-01

    In vitamin D-deficient rats, impaired intestinal phosphorus (P) absorption can be corrected by 1,25-dihydroxyvitamin D(3)[1,25-(OH)(2)D(3)]. In the present study, it was investigated whether changes in 1,25-(OH)(2)D(3) production can influence intestinal P transport also in animals with a normal supply of vitamin D. The intestinal P absorption was evaluated in rats using both the in situ duodenal loop technique and the determination of the overall gastrointestinal absorption under three conditions known to influence the production of 1,25-(OH)(2)D(3): (a) variation in dietary P, (b) thyroparathyroidectomy (TPTX) with or without administration of parathyroid hormone (PTH), and (c) treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP). In all circumstances changes in duodenal absorption paralleled the changes in the overall fractional absorption. (a) Lowering dietary P stimulated P absorption. (b) TPTX decreased P absorption. This effect was corrected either by the administration of PTH or by the administration of 1,25-(OH)(2)D(3). (c) EHDP, when given at a dose known to inhibit 1,25-(OH)(2)D(3) formation, decreased the duodenal P absorption in both intact and TPTX animals. This effect was corrected by 1,25-(OH)(2)D(3). In the TPTX-EHDP-treated animals, the administration of PTH did not rectify the low duodenal P absorption. These results support the thesis that, in rats with normal vitamin D supply, variations in the endogenous production of 1,25-(OH)(2)D(3) change the rate of P absorption. However, these changes are in such magnitude that they are of relatively small importance when compared to the effect of variation in the dietary intake of P. These results also strongly suggest that the action of PTH on duodenal P transport is mediated by its effect on 1,25-(OH)(2)D(3) production, inasmuch as the effect of the hormone is abolished after blocking the renal 1-hydroxylation with EHDP.

  7. 1,25(OH) sub 2 D sub 3 and Ca-binding protein in fetal rats: Relationship to the maternal vitamin D status

    SciTech Connect

    Verhaeghe, J.; Thomasset, M.; Brehier, A.; Van Assche, F.A.; Bouillon, R. Institut National de la Sante et de la Recherche Medical )

    1988-04-01

    The autonomy and functional role of fetal 1,25-dihydroxyvitamin D{sub 3} (1,25(OH){sub 2}D{sub 3}) were investigated in nondiabetic and diabetic BB rats fed diets containing 0.85% calcium-0.7% phosphorus or 0.2% calcium and phosphorus and in semistarved rats on the low calcium-phosphorus diet. The changes in maternal and fetal plasma 1,25(OH){sub 2}D{sub 3} were similar: the levels were increased by calcium-phosphorus restriction and decreased by diabetes and semistarvation. Maternal and fetal 1,25(OH){sub 2}D{sub 3} levels were correlated. The vitamin D-dependent calcium-binding proteins (CaBP{sub 9K} and CaBP{sub 28K}) were measured in multiple maternal and fetal tissues and in the placenta of nondiabetic, diabetic, and calcium-phosphorus-restricted rats. The distributions of CaBP{sub 9K} and CaBP{sub 28K} in the pregnant rat were similar to that of the growing rat. The increased maternal plasma 1,25(OH){sub 2}D{sub 3} levels in calcium-phosphorus-restricted rats were associated with higher duodenal CaBP{sub 9K} and renal CaBPs, but placental CaBP{sub 9K} was not different. In diabetic pregnant rats, duodenal CaBP{sub 9K} was not different. In diabetic pregnant rats, duodenal CaBP{sub 9K} tended to be lower, while renal CaBPs were normal; placental CaBP{sub 9K} was decreased. The results indicate that in the rat fetal 1,25(OH){sub 2}D{sub 3} depends on maternal 1,25(OH){sub 2}D{sub 3} or on factors regulating maternal 1,25(OH){sub 2}D{sub 3}. The lack of changes in fetal CaBP in the presence of altered fetal plasma 1,25(OH){sub 2}D{sub 3} levels confirms earlier data showing that 1,25(H){sub 2}D{sub 3} has a limited hormonal function during perinatal development in the rat.

  8. [The role of vitamin D3 in the regulation of the mineral metabolism in experimental type 1 diabetes].

    PubMed

    Labudzynskyi, D O; Lisakovska, O A; Shymanskyy, I A; Riasnyi, V M; Veliky, N N

    2014-01-01

    Diabetes was shown to be associated with a considerable lowering of 25(OH)D3 in blood serum of mice. Vitamin D3 deficiency was correlated with impaired mineral metabolism in bone tissue, indicating the development of secondary osteoporosis. A decrease in weight, length and diameter (diaphysis, proximal metaepiphysis) of tibia in diabetic animals was observed as compared with control. Diabetes caused hypocalcemia, hypophosphatemia and increased enzymatic activity of alkaline phosphatase (ALP) and its isoenzymes in serum. This changes were accompanied by the impairments of vitamin D3 25-hydroxylase isoforms (CYP27A1 and CYP2R1) expression, which are the main enzymes of cholecalciferol biotransformation to 25(OH)D3 - precursor of hormonally active form of vitamin D3. A decrease in bone resorption processes was established after vitamin D3 administration as it is evident from normalization of bone morphometrical parameters and mineral metabolism in diabetic mice. Vitamin D3 ability to counter diabetes-induced alterations in bone tissue can be ascribed, at least in part, to its positive effects on the formation of vitamin D3 hormonally active forms.

  9. Effect of Vitamin D3 Supplementation in Black and in White Children: A Randomized, Placebo-Controlled Trial

    PubMed Central

    Moore, Charity G.; Yabes, Jonathan; Olabopo, Flora; Haralam, Mary Ann; Comer, Diane; Bogusz, Jaimee; Nucci, Anita; Sereika, Susan; Dunbar-Jacob, Jacqueline; Holick, Michael F.; Greenspan, Susan L.

    2015-01-01

    Context: Dosages of vitamin D necessary to prevent or treat vitamin D deficiency in children remain to be clarified. Objective: To determine the effects of vitamin D3 1000 IU/d on serum 25-hydroxyvitamin D [25(OH)D], PTH, and markers of bone turnover (osteocalcin and collagen type 1 cross-linked C-telopeptide) in black children and white children, and to explore whether there is a threshold level of 25(OH)D associated with maximal suppression of serum PTH concentration. Design: Healthy 8- to 14-year-old Pittsburgh-area black (n = 84) and white (n = 73) children not receiving vitamin supplements, enrolled from October through March from 2008 through 2011, were randomized to vitamin D3 1000 IU or placebo daily for 6 months. Results: The mean baseline concentration of 25(OH)D was <20 ng/mL in both the vitamin D-supplemented group and the placebo group (19.8 ± 7.6 and 18.8 ± 6.9 ng/mL, respectively). The mean concentration was higher in the supplemented group than in the placebo group at 2 months (26.4 ± 8.1 vs 18.9 ± 8.1 ng/mL; P < .0001) and also at 6 months (26.7 ± 7.6 vs 22.4 ± 7.3; P = .003), after adjusting for baseline 25(OH)D, race, gender, pubertal status, dietary vitamin D intake, body mass index, and sunlight exposure. Increases were only significant in black children, when examined by race. The association between 25(OH)D and PTH concentrations was inverse and linear, without evidence of a plateau. Overall, vitamin D supplementation had no effect on PTH and bone turnover. Conclusions: Vitamin D3 supplementation with 1000 IU/d in children with mean baseline 25(OH)D concentration <20 ng/mL effectively raised their mean 25(OH)D concentration to ≥20 ng/mL but failed to reach 30 ng/mL. Vitamin D supplementation had no effect on PTH concentrations. PMID:26091202

  10. The Impact of Vitamin D3 Supplementation on Mechanisms of Cell Calcium Signaling in Chronic Kidney Disease.

    PubMed

    Lajdova, Ingrid; Spustova, Viera; Oksa, Adrian; Kaderjakova, Zuzana; Chorvat, Dusan; Morvova, Marcela; Sikurova, Libusa; Marcek Chorvatova, Alzbeta

    2015-01-01

    Intracellular calcium concentration in peripheral blood mononuclear cells (PBMCs) of patients with chronic kidney disease (CKD) is significantly increased, and the regulatory mechanisms maintaining cellular calcium homeostasis are impaired. The purpose of this study was to examine the effect of vitamin D3 on predominant regulatory mechanisms of cell calcium homeostasis. The study involved 16 CKD stages 2-3 patients with vitamin D deficiency treated with cholecalciferol 7000-14000 IU/week for 6 months. The regulatory mechanisms of calcium signaling were studied in PBMCs and red blood cells. After vitamin D3 supplementation, serum concentration of 25(OH)D3 increased (P < 0.001) and [Ca(2+)]i decreased (P < 0.001). The differences in [Ca(2+)]i were inversely related to differences in 25(OH)D3 concentration (P < 0.01). Vitamin D3 supplementation decreased the calcium entry through calcium release activated calcium (CRAC) channels and purinergic P2X7 channels. The function of P2X7 receptors was changed in comparison with their baseline status, and the expression of these receptors was reduced. There was no effect of vitamin D3 on P2X7 pores and activity of plasma membrane Ca(2+)-ATPases. Vitamin D3 supplementation had a beneficial effect on [Ca(2+)]i decreasing calcium entry via CRAC and P2X7 channels and reducing P2X7 receptors expression.

  11. Effect of a combined therapeutic approach of intensive lipid management, omega-3 fatty acid supplementation, and increased serum 25 (OH) vitamin D on coronary calcium scores in asymptomatic adults.

    PubMed

    Davis, William; Rockway, Susie; Kwasny, Mary

    2009-01-01

    The impact of intensive lipid management, omega-3 fatty acid, and vitamin D3 supplementation on atherosclerotic plaque was assessed through serial computed tomography coronary calcium scoring (CCS). Low-density lipoprotein cholesterol reduction with statin therapy has not been shown to reduce or slow progression of serial CCS in several recent studies, casting doubt on the usefulness of this approach for tracking atherosclerotic progression. In an open-label study, 45 male and female subjects with CCS of > or = 50 without symptoms of heart disease were treated with statin therapy, niacin, and omega-3 fatty acid supplementation to achieve low-density lipoprotein cholesterol and triglycerides < or = 60 mg/dL; high-density lipoprotein > or = 60 mg/dL; and vitamin D3 supplementation to achieve serum levels of > or = 50 ng/mL 25(OH) vitamin D, in addition to diet advice. Lipid profiles of subjects were significantly changed as follows: total cholesterol -24%, low-density lipoprotein -41%; triglycerides -42%, high-density lipoprotein +19%, and mean serum 25(OH) vitamin D levels +83%. After a mean of 18 months, 20 subjects experienced decrease in CCS with mean change of -14.5% (range 0% to -64%); 22 subjects experienced no change or slow annual rate of CCS increase of +12% (range 1%-29%). Only 3 subjects experienced annual CCS progression exceeding 29% (44%-71%). Despite wide variation in response, substantial reduction of CCS was achieved in 44% of subjects and slowed plaque growth in 49% of the subjects applying a broad treatment program. PMID:19092644

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

    PubMed

    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.

  13. Vitamin D3 supplementation scheme in HIV-infected patients based upon pharmacokinetic modelling of 25-hydroxycholecalciferol

    PubMed Central

    Foissac, Frantz; Tréluyer, Jean-Marc; Souberbielle, Jean-Claude; Rostane, Hafeda; Urien, Saïk; Viard, Jean-Paul

    2013-01-01

    Aims Vitamin D deficiency is prevalent in HIV-infected patients and has been associated with osteopenia and HIV disease progression. Our aims were to investigate the pharmacokinetics of 25-hydroxycholecalciferol [25(OH)D], the effect of antiretroviral treatment (ARV) and others factors that may influence the pharmacokinetics, and to determine a vitamin D3 dosing scheme to reach the 30 ng ml−1 threshold (defined as 25(OH)D sufficiency). Methods This monocentric retrospective study included 422 HIV-infected patients aged 16 to 85 years. A total of 723 25(OH)D concentrations were available for pharmacokinetic evaluation and a population pharmacokinetic model was developed with MONOLIX 3.2. Results Median 25(OH)D at baseline was 16 ng ml−1 (interquartile range 11–23 ng ml−1) for the total population, 17% of patient had concentrations below 10 ng ml−1, 68% between 10 and 30 ng ml−1 and 15% above 30 ng ml−1. 25(OH)D pharmacokinetics were best described by a one compartment model with an additional endogenous production. The effects of season and skin phototype were significant on production rate. The endogenous production was 20% lower in non-white skin phototype patients and was decreased by 16% during autumn, winter and spring. No significant differences in 25(OH)D concentrations were related to antiretroviral drugs (ARV). To obtain concentrations between 30 and 80 ng ml−1, the dosing recommendation was 100 000 IU every month. Conclusions Season and skin phototype had an influence on the endogenous production of 25(OH)D. However no effect of ARV was found. A dosing scheme to reach sufficient 25(OH)D concentrations is proposed. PMID:23072545

  14. 21 CFR 582.5953 - Vitamin D3.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Vitamin D3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D3. (a) Product. Vitamin D3. (b) Conditions of use. This substance is...

  15. 21 CFR 582.5953 - Vitamin D 3.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Vitamin D 3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D 3. (a) Product. Vitamin D3. (b) Conditions of use. This substance...

  16. 21 CFR 582.5953 - Vitamin D3.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Vitamin D3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D3. (a) Product. Vitamin D3. (b) Conditions of use. This substance is...

  17. 21 CFR 582.5953 - Vitamin D 3.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Vitamin D 3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D 3. (a) Product. Vitamin D3. (b) Conditions of use. This substance...

  18. 21 CFR 582.5953 - Vitamin D3.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Vitamin D3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D3. (a) Product. Vitamin D3. (b) Conditions of use. This substance is...

  19. Retinoid X receptor:vitamin D3 receptor heterodimers promote stable preinitiation complex formation and direct 1,25-dihydroxyvitamin D3-dependent cell-free transcription.

    PubMed Central

    Lemon, B D; Fondell, J D; Freedman, L P

    1997-01-01

    The numerous members of the steroid/nuclear hormone receptor superfamily act as direct transducers of circulating signals, such as steroids, thyroid hormone, and vitamin or lipid metabolites, and modulate the transcription of specific target genes, primarily as dimeric complexes. The receptors for 9-cis retinoic acid and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], RXR and VDR, respectively, as members of this superfamily, form a heterodimeric complex and bind cooperatively to vitamin D responsive elements (VDREs) to activate or repress the transcription of a multitude of genes which regulate a variety of physiological functions. To directly investigate RXR- and VDR-mediated transactivation, we developed a cell-free transcription system for 1,25(OH)2D3 signaling by utilizing crude nuclear extracts and a G-free cassette-based assay. Transcriptional enhancement in vitro was dependent on purified, exogenous RXR and VDR and was responsive to physiological concentrations of 1,25(OH)2D3. We found that RXR and VDR transactivated selectively from VDRE-linked templates exclusively as a heterodimeric complex, since neither receptor alone enhanced transcription in vitro. By the addition of low concentrations of the anionic detergent Sarkosyl to limit cell-free transcription to a single round and the use of agarose gel mobility shift experiments to assay factor complex assembly, we observed that 1,25(OH)2D3 enhanced RXR:VDR-mediated stabilization or assembly of preinitiation complexes to effect transcriptional enhancement from VDRE-linked promoter-containing DNA. PMID:9121440

  20. A novel compound heterozygous ROMK mutation presenting as late onset Bartter syndrome associated with nephrocalcinosis and elevated 1,25(OH)(2) vitamin D levels.

    PubMed

    Sharma, Amita; Linshaw, Micheal A

    2011-08-01

    Bartter syndrome (BS) is a rare renal tubular disorder presenting with hypokalemic metabolic alkalosis, which is classified into five types. KCNJ1 mutations usually cause the neonatal form of BS, type II BS (OMIM 241200). However, this report concerns a female patient with a novel, compound heterozygous KCNJ1 mutation that causes late-onset BS. The unique clinical findings of this case include persistently elevated 1,25(OH)(2) vitamin D levels, possibly due to increase prostaglandin E(2) levels, and medullary nephrocalcinosis. Treatment with COX-2 inhibitors resolved her hypercalciuria and improved her height and weight; renal function remains stable and there is no progression of nephrocalcinosis. PMID:21431899

  1. Mineralization of three-dimensional osteoblast cultures is enhanced by the interaction of 1α,25-dihydroxyvitamin D3 and BMP2 via two specific vitamin D receptors.

    PubMed

    Chen, Jiaxuan; Dosier, Christopher R; Park, Jung Hwa; De, Subhendu; Guldberg, Robert E; Boyan, Barbara D; Schwartz, Zvi

    2016-01-01

    1α,25-Dihydroxyvitamin D3 [1α,25(OH)2D3] and bone morphogenetic protein-2 (BMP2) are both used to stimulate osteoblastic differentiation. 1α,25(OH)2D3 regulates osteoblasts through classical steroid hormone receptor mechanisms and through rapid responses that are mediated by two receptors, the traditional vitamin D receptor (VDR) and protein disulphide isomerase family A member 3 (Pdia3). The interaction between 1α,25(OH)2D3 and BMP2, especially in three-dimensional (3D) culture, and the roles of the two vitamin D receptors in this interaction are not well understood. We treated wild-type (WT), Pdia3-silenced (Sh-Pdia3) and VDR-silenced (Sh-VDR) pre-osteoblastic MC3T3-E1 cells with either 1α,25(OH)2D3, or BMP2, or with 1α,25(OH)2D3 and BMP2 together, and measured osteoblast marker expression in 2D culture and mineralization in a 3D poly(ε-caprolactone)-collagen scaffold model. Quantitative PCR showed that silencing Pdia3 or VDR had a differential effect on baseline expression of osteoblast markers. 1α,25(OH)2D3 + BMP2 caused a synergistic increase in osteoblast marker expression in WT cells, while silencing either Pdia3 or VDR attenuated this effect. 1α,25(OH)2D3 + BMP2 also caused a synergistic increase in Dlx5 in both silenced cell lines. Micro-computed tomography (μCT) showed that the mineralized volume of untreated Sh-Pdia3 and Sh-VDR 3D cultures was greater than that of WT. 1α,25(OH)2D3 reduced mineral in WT and Sh-VDR cultures; BMP2 increased mineralization; and 1α,25(OH)2D3 + BMP2 caused a synergistic increase, but only in WT cultures. SEM showed that mineralized matrix morphology in 3D cultures differed for silenced cells compared to WT cells. These data indicate a synergistic crosstalk between 1α,25(OH)2D3 and BMP2 toward osteogenesis and mineral deposition, involving both VDR and Pdia3.

  2. Dietary vitamin D3 deficiency alters intestinal mucosal defense and increases susceptibility to Citrobacter rodentium-induced colitis.

    PubMed

    Ryz, Natasha R; Lochner, Arion; Bhullar, Kirandeep; Ma, Caixia; Huang, Tina; Bhinder, Ganive; Bosman, Else; Wu, Xiujuan; Innis, Sheila M; Jacobson, Kevan; Vallance, Bruce A

    2015-11-01

    Vitamin D deficiency affects more that 1 billion people worldwide. Although thought to increase risk of bacterial infections, the importance of vitamin D on host defense against intestinal bacterial pathogens is currently unclear since injection of the active form of vitamin D, 1,25(OH)2D3, increased susceptibility to the enteric bacterial pathogen Citrobacter rodentium by suppressing key immune/inflammatory factors. To further characterize the role of vitamin D during bacteria-induced colitis, we fed weanling mice either vitamin D3-deficient or vitamin D3-sufficient diets for 5 wk and then challenged them with C. rodentium. Vitamin D3-deficient mice lost significantly more body weight, carried higher C. rodentium burdens, and developed worsened histological damage. Vitamin D3-deficient mice also suffered greater bacterial translocation to extra-intestinal tissues, including mesenteric lymph nodes, spleen, and liver. Intestinal tissues of infected vitamin D3-deficient mice displayed increased inflammatory cell infiltrates as well as significantly higher gene transcript levels of inflammatory mediators TNF-α, IL-1β, IL-6, TGF-β, IL-17A, and IL-17F as well as the antimicrobial peptide REG3γ. Notably, these exaggerated inflammatory responses accelerated the loss of commensal microbes and were associated with an impaired ability to detoxify bacterial lipopolysaccharide. Overall, these studies show that dietary-induced vitamin D deficiency exacerbates intestinal inflammatory responses to infection, also impairing host defense.

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

    PubMed

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

    2000-01-01

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

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

    SciTech Connect

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

    1981-07-01

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

  5. Serum 25(OH) Vitamin D levels is not associated with disability in multiple sclerosis patients: A case-control study

    PubMed Central

    Nikanfar, Masoud; Taheri-Aghdam, Ali Akbar; Yazdani, Maria; Shaafi, Sheida; Masoudian, Nooshin; Akbari, Hossein; Youhanaee, Parisa; Abbaszadeh, Hamzeh

    2015-01-01

    Background: It seems that serum vitamin D levels are one of the potential environmental factors affecting the severity of multiple sclerosis (MS). In this study, we aim to evaluate vitamin D levels in MS patients and healthy subjects and assess the relationship between vitamin D level and disability. Methods: In this case-control study, 168 rapid relapsing MS patients and 168 matched healthy controls were randomly included in this study. Demographic characteristics and serum vitamin D levels for patients and controls, as well as expanded disability status scale (EDSS), duration of disease and diagnostic lag for patients were evaluated. We followed up patients for 6 months and relapses were recorded. Results: The mean serum vitamin D levels were 19.16 ± 17.37 inpatients and 25.39 ± 19.67 in controls (P = 0.560). The mean serum vitamin D levels were 12.65 ± 13.3 in patients with relapses and 22.08 ± 18.22 in patients without any relapses (P < 0.001). There was no significant correlation between EDSS score and serum vitamin D levels (r = −0.08, P = 0.280). There was a significant positive correlation between EDSS score and disease duration (r = 0.52, P < 0.001). Conclusion: In conclusion, vitamin D level in patients with MS was significantly lower than the healthy subjects, but no significant relationship was found between vitamin D levels and disability. Our findings did not suggest a protective role for serum vitamin D levels against disability. PMID:25874052

  6. Conformational change and enhanced stabilization of the vitamin D receptor by the 1,25-dihydroxyvitamin D3 analog KH1060.

    PubMed Central

    van den Bemd, G C; Pols, H A; Birkenhäger, J C; van Leeuwen, J P

    1996-01-01

    The 1,25-dihydroxyvitamin D3 [1,25-(OH)2vitamin D3] analog KH1060 exerts very potent effects on cell proliferation and cell differentiation via the vitamin D receptor (VDR). However, the activities of KH1060 are not associated with an increased affinity for the VDR. We now show that increased stabilization of the VDR-KH1060 complex could be an explanation for its high potencies. VDR half-life studies performed with cycloheximide-translational blocked rat osteoblast-like ROS 17/2.8 cells demonstrated that, in the absence of ligand, VDR levels rapidly decreased. After 2 hr, less than 10% of the initial VDR level could be measured. In the presence of 1,25-(OH)2vitamin D3, the VDR half-life was 15 hr. After 24 hr. less than 20% of the initial VDR content was detectable, whereas, at this time-point, when the cells were incubated with KH1060 80% of the VDR was still present. Differences in 1,25-(OH)2vitamin D3- and KH1060-induced conformational changes of the VDR could underlie the increased VDR stability. As assessed by limited proteolytic digestion analysis, both 1,25-(OH)2vitamin D3 and KH1060 caused a specific conformational change of the VDR. Compared with 1,25-(OH)2vitamin D3, KH1060 induced a conformational change that led to a far more dramatic protection of the VDR against proteolytic degradation. In conclusion, the altered VDR stability and the possibly underlying change in VDR conformation caused by KH1060 could be an explanation for its enhanced bioactivity. Images Fig. 3 Fig. 4 Fig. 5 Fig. 7 PMID:8855240

  7. 1,25-Dihydroxyvitamin D3 Controls a Cohort of Vitamin D Receptor Target Genes in the Proximal Intestine That Is Enriched for Calcium-regulating Components.

    PubMed

    Lee, Seong Min; Riley, Erin M; Meyer, Mark B; Benkusky, Nancy A; Plum, Lori A; DeLuca, Hector F; Pike, J Wesley

    2015-07-17

    1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) plays an integral role in calcium homeostasis in higher organisms through its actions in the intestine, kidney, and skeleton. Interestingly, although several intestinal genes are known to play a contributory role in calcium homeostasis, the entire caste of key components remains to be identified. To examine this issue, Cyp27b1 null mice on either a normal or a high calcium/phosphate-containing rescue diet were treated with vehicle or 1,25(OH)2D3 and evaluated 6 h later. RNA samples from the duodena were then subjected to RNA sequence analysis, and the data were analyzed bioinformatically. 1,25(OH)2D3 altered expression of large collections of genes in animals under either dietary condition. 45 genes were found common to both 1,25(OH)2D3-treated groups and were composed of genes previously linked to intestinal calcium uptake, including S100g, Trpv6, Atp2b1, and Cldn2 as well as others. An additional distinct network of 56 genes was regulated exclusively by diet. We then conducted a ChIP sequence analysis of binding sites for the vitamin D receptor (VDR) across the proximal intestine in vitamin D-sufficient normal mice treated with vehicle or 1,25(OH)2D3. The residual VDR cistrome was composed of 4617 sites, which was increased almost 4-fold following hormone treatment. Interestingly, the majority of the genes regulated by 1,25(OH)2D3 in each diet group as well as those found in common in both groups contained frequent VDR sites that likely regulated their expression. This study revealed a global network of genes in the intestine that both represent direct targets of vitamin D action in mice and are involved in calcium absorption.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  9. 1Alpha,25-(OH)2D3 acts in the early phase of osteoblast differentiation to enhance mineralization via accelerated production of mature matrix vesicles.

    PubMed

    Woeckel, V J; Alves, R D A M; Swagemakers, S M A; Eijken, M; Chiba, H; van der Eerden, B C J; van Leeuwen, J P T M

    2010-11-01

    1Alpha,25-dihydroxyitamin D(3) (1,25D3) deficiency leads to impaired bone mineralization. We used the human pre-osteoblastic cell line SV-HFO, which forms within 19 days of culture an extracellular matrix that starts to mineralize around day 12, to examine the mechanism by which 1,25D3 regulates osteoblasts and directly stimulates mineralization. Time phase studies showed that 1,25D3 treatment prior to the onset of mineralization, rather than during mineralization led to accelerated and enhanced mineralization. This is supported by the observation of unaltered stimulation by 1,25D3 even when osteoblasts were devitalized just prior to onset of mineralization and after 1,25D3 treatment. Gene Chip expression profiling identified the pre-mineralization and mineralization phase as two strongly distinctive transcriptional periods with only 0.6% overlap of genes regulated by 1,25D3. In neither phase 1,25D3 significantly altered expression of extracellular matrix genes. 1,25D3 significantly accelerated the production of mature matrix vesicles (MVs) in the pre-mineralization. Duration rather than timing determined the extent of the 1,25D3 effect. We propose the concept that besides indirect effects via intestinal calcium uptake 1,25D3 directly accelerates osteoblast-mediated mineralization via increased production of mature MVs in the period prior to mineralization. The accelerated deposition of mature MVs leads to an earlier onset and higher rate of mineralization. These effects are independent of changes in extracellular matrix protein composition. These data on 1,25D3, mineralization, and MV biology add new insights into the role of 1,25D3 in bone metabolism and emphasize the importance of MVs in bone and maintaining bone health and strength by optimal mineralization status.

  10. Retention of bone strength by feeding of milk and dairy products in ovariectomized rats: involvement of changes in serum levels of 1alpha, 25(OH)2D3 and FGF23.

    PubMed

    Tanabe, Rieko; Haraikawa, Mayu; Sogabe, Natsuko; Sugimoto, Aoi; Kawamura, Yuka; Takasugi, Satoshi; Nagata, Masashi; Nakane, Ayako; Yamaguchi, Akira; Iimura, Tadahiro; Goseki-Sone, Masae

    2013-06-01

    The current study compared the effects of milk, yogurt or whey on the bone strength, body composition and serum biomarkers. Forty 12-week-old female Sprague-Dawley rats were ovariectomized (OVX), and another nine rats received a sham operation (Sham-Cont). After a 1-week recovery period, the OVX rats were divided into four dietary groups: OVX-control group (OVX-Cont), 17% skimmed milk powder diet group (OVX-Milk), 17% powdered fermented milk diet group (OVX-Yogurt) and 12% whey powder and 6% whey protein extract diet group (OVX-Whey) (n=10 in each group). The protein, nitrogen, fat, calcium and phosphorus contents of the experimental diets were adjusted to be similar to the control diet (AIN-93M). Eighty-four days after the beginning of the experimental diet, the total bone mineral density and bone mineral contents of lumbar vertebrae were significantly higher in the OVX-Milk and OVX-Whey groups than in the OVX-Cont group. Furthermore, the level of 1alpha, 25-dihydroxyvitamin D3 [1alpha, 25(OH)2D3] was significantly lower, while the serum level of FGF23 was significantly higher in the OVX-Milk, OVX-Yogurt and OVX-Whey groups than in the OVX-Cont group. These findings suggest that milk and the dairy products could improve bone metabolism in a postmenopausal animal model at least partly through changing the balance between 1alpha, 25(OH)2D3 and FGF23.

  11. Use of Vitamin D3 and Its Metabolites in Broiler Chicken Feed on Performance, Bone Parameters and Meat Quality

    PubMed Central

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

    2013-01-01

    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 (p<0.05). No significant differences were noted among the treatments (p>0.05) 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. PMID:25049804

  12. In vitro effects of 1α,25(OH)₂D₃-glycosides from Solbone A (Solanum glaucophyllum leaves extract; Herbonis AG) compared to synthetic 1α,25(OH)₂D₃ on myogenesis.

    PubMed

    Gili, Valeria; Pardo, Verónica Gonzalez; Ronda, Ana C; De Genaro, Pablo; Bachmann, Heini; Boland, Ricardo; de Boland, Ana Russo

    2016-05-01

    The presence of glycoside derivatives of 1α,25(OH)2D3 endows plants to gradual release of the free bioactive form of 1α,25(OH)2D3 from its glycoconjugates by endogenous animal tissue glycosidases. This results in increased half-life of the hormone in blood when purified plant fractions are administered for therapeutic purposes. In this work, we evaluated the role 1α,25(OH)2D3-glycosides enriched natural product (Solbone A) from Solanum glaucophyllum leaf extract compared with synthetic 1α,25(OH)2D3 on myogenic differentiation in C2C12 myoblasts. For these, differentiation markers and myogenic parameters were studied in C2C12 myoblasts. Results showed that Solbone A, likewise the synthetic hormone, increased creatine kinase activity at day 2 after differentiation induction (60%, p<0.05). Solbone A and synthetic 1α,25(OH)2D3 increased vitamin D3 receptor protein expression at 10nM (50% and 30%, respectively) and the transcription factor myogenin (80%, p<0.05). However, tropomyosin expression was not affected by both compounds. In addition, myosin heavy chain (MHC) protein expression was increased 30% at day 2 of differentiation. Solbone A or synthetic 1α,25(OH)2D3 had no effects on myogenin nor MHC cell localization. Cellular mass increased with myogenesis progression, being Solbone A more effective than synthetic 1α,25(OH)2D3. Finally, Solbone A, as well as synthetic 1α,25(OH)2D3, augmented the index fusion of cultured muscle fibers. In conclusion, these results demonstrated that Solbone A exhibit at least equal or greater effects on early myoblast differentiation as synthetic hormone, suggesting that plant glycosides could be an effective, accessible and cheaper substitute for synthetic 1α,25(OH)2D3 to promote muscle growth. PMID:26968127

  13. High-dose vitamin D3 supplementation is a requisite for modulation of skin-homing markers on regulatory T cells in HIV-infected patients.

    PubMed

    Khoo, Ai-Leng; Koenen, Hans J P M; Michels, Meta; Ooms, Sharon; Bosch, Marjolein; Netea, Mihai G; Joosten, Irma; van der Ven, André J A M

    2013-02-01

    Vitamin D(3) is known to have an effect on the immune function. We investigated the immunomodulatory capability of vitamin D(3) in HIV-infected patients and studied the expression of chemokine receptors on regulatory T cells (Treg). Vitamin D(3)-deficient HIV-1-seropositive subjects were treated with cholecalciferol (vitamin D(3)) at a dose of 800 IU daily for 3 months (n=9) or 25,000 IU weekly for 2 months (n=7). Peripheral blood mononuclear cells (PBMCs) were isolated and analyzed for skin-homing (CCR4 and CCR10) and gut-homing (CCR9 and integrin α(4)β(7)) marker expression on Treg, by flow cytometry, before and after supplementation. Serum 25(OH)D(3) and parathyroid hormone (PTH) levels were determined at baseline and after the treatment period. Weekly doses of 25,000 IU cholecalciferol effectively achieved the optimal target serum 25(OH)D(3) concentration of >75 nmol/liter (30 ng/ml) in HIV-infected patients. High-dose cholecalciferol supplementation differentially influenced skin-homing markers on Treg with an increased level of CCR10 expression and while a reduction in CCR4 expression level was observed together with a lower percentage of Treg expressing CCR4. For both dosing regimens, there were no significant differences in the expression of gut-homing markers, CCR9, and integrin α(4)β(7). High-dose vitamin D(3) supplementation is needed to reverse vitamin D(3) deficiency in HIV-infected individuals and this results in modulation of skin-homing markers but not gut-homing markers expression on Treg. At a standard dose of 800 IU/day, vitamin D(3) is not effective in achieving an optimal 25(OH)D(3) concentration in patients with an underlying T cell dysfunction and is unable to exert any immunomodulatory effects.

  14. Serum Vitamin D3 Level in Patients with Female Pattern Hair Loss

    PubMed Central

    Banihashemi, Mahnaz; Nahidi, Yalda; Meibodi, Naser Tayyebi; Jarahi, Lida; Dolatkhah, Mojgan

    2016-01-01

    Background: Female pattern hair loss (FPHL) is the most common cause of alopecia in women, characterized by diffuse nonscarring hair loss in frontal, central, and parietal areas of the scalp. Pathophysiology of FPHL is still not well known, and it is probably a multifactorial genetic trait. FPHL is also observed in women without increased androgen levels, which raises the likelihood of androgen-independent mechanisms and explains the lack of response to antiandrogen treatments in some patients. Vitamin D is a factor that has recently been considered in dealing with these patients. The purpose of this study was to evaluate the serum levels of Vitamin D in patients with FPHL and compare it with healthy controls. Methods: In this case-control study, 45 women with FPHL were evaluated as well as the same number of healthy women matched for age, hours spent under sunlight per day, and body mass index. Serum 25(OH) D3 level was measured using ELISA. Results: 60% of FPHL patients were in 15–30 years old age group with the mean standard deviation (SD) age of 29.11 (7.30) years. In the majority of patients (66.7%), severity of hair loss was Ludwig I. Mean (SD) serum Vitamin D3 level in patient and control group was 13.45 (8.40) and 17.16 (8.96), respectively. T-test showed a significant difference between the two groups in terms of Vitamin D3 serum levels (P = 0.04). Conclusions: This study indicated the correlation between the incidence of FPHL and decreased serum levels of Vitamin D3. It is recommended to evaluate serum Vitamin D3 levels as well as other hormone assays in these patients. PMID:27625563

  15. Serum Vitamin D3 Level in Patients with Female Pattern Hair Loss

    PubMed Central

    Banihashemi, Mahnaz; Nahidi, Yalda; Meibodi, Naser Tayyebi; Jarahi, Lida; Dolatkhah, Mojgan

    2016-01-01

    Background: Female pattern hair loss (FPHL) is the most common cause of alopecia in women, characterized by diffuse nonscarring hair loss in frontal, central, and parietal areas of the scalp. Pathophysiology of FPHL is still not well known, and it is probably a multifactorial genetic trait. FPHL is also observed in women without increased androgen levels, which raises the likelihood of androgen-independent mechanisms and explains the lack of response to antiandrogen treatments in some patients. Vitamin D is a factor that has recently been considered in dealing with these patients. The purpose of this study was to evaluate the serum levels of Vitamin D in patients with FPHL and compare it with healthy controls. Methods: In this case-control study, 45 women with FPHL were evaluated as well as the same number of healthy women matched for age, hours spent under sunlight per day, and body mass index. Serum 25(OH) D3 level was measured using ELISA. Results: 60% of FPHL patients were in 15–30 years old age group with the mean standard deviation (SD) age of 29.11 (7.30) years. In the majority of patients (66.7%), severity of hair loss was Ludwig I. Mean (SD) serum Vitamin D3 level in patient and control group was 13.45 (8.40) and 17.16 (8.96), respectively. T-test showed a significant difference between the two groups in terms of Vitamin D3 serum levels (P = 0.04). Conclusions: This study indicated the correlation between the incidence of FPHL and decreased serum levels of Vitamin D3. It is recommended to evaluate serum Vitamin D3 levels as well as other hormone assays in these patients.

  16. Effect of 25(OH) vitamin D reference method procedure (RMP) alignment on clinical measurements obtained with the IDS-iSYS chemiluminescent-based automated analyzer.

    PubMed

    Simpson, Christine A; Cusano, Anna Maria; Bihuniak, Jessica; Walker, Joanne; Insogna, Karl L

    2015-04-01

    The Vitamin D Standardization Program (VDSP) has identified ID-LC/MS/MS as the reference method procedure (RMP) for 25(OH) vitamin D and NIST Standard SRM2972 as the standard reference material (SRM). As manufacturers align their products to the RMP and NIST standard, a concern is that results obtained in aligned assays will be divergent from those obtained with pre-alignment assays. The Immunodiagnostic Systems Ltd., chemiluminescent, 25(OH) vitamin D iSYS platform assay, was recently harmonized to the RMP. To determine the impact of standardization on results obtained with iSYS reagents, 119 single donor serum samples from eight different disease categories were analyzed in four non-standardized and two standardized iSYS assays. There were strong correlations between the four non-standardized and two standardized assays with Spearman's rank r values between 0.975 and 0.961 and four of the eight r values were >0.97. R(2) values for the eight best-fit linear regression equations ranging between 0.947 and 0.916. None of the slopes were found to be significantly different from one another. Bland-Altman plots showed that the bias was comparable when each of the four non-standardized assays was compared to either of the standardized assays. When the data were segregated in values between 6 and 49ng/mL (15-122nmol/L) or between 50 and 100ng/mL (125-250nmol/L) significant associations remained between results obtained with non-standardized and standardized calibrators regardless of the absolute value. When five recent DEQAS unknowns were analyzed in one non-standardized and one standardized assay the mean percent difference from the NIST target in values obtained using standardized vs. non-standardized calibrators were not significantly different. Finally, strong and statistically significant associations between the results were obtained using non-standardized and standardized assays for six of eight clinical conditions. The only exceptions were hypocalcemia and breast

  17. Effect of 25(OH) vitamin D reference method procedure (RMP) alignment on clinical measurements obtained with the IDS-iSYS chemiluminescent-based automated analyzer.

    PubMed

    Simpson, Christine A; Cusano, Anna Maria; Bihuniak, Jessica; Walker, Joanne; Insogna, Karl L

    2015-04-01

    The Vitamin D Standardization Program (VDSP) has identified ID-LC/MS/MS as the reference method procedure (RMP) for 25(OH) vitamin D and NIST Standard SRM2972 as the standard reference material (SRM). As manufacturers align their products to the RMP and NIST standard, a concern is that results obtained in aligned assays will be divergent from those obtained with pre-alignment assays. The Immunodiagnostic Systems Ltd., chemiluminescent, 25(OH) vitamin D iSYS platform assay, was recently harmonized to the RMP. To determine the impact of standardization on results obtained with iSYS reagents, 119 single donor serum samples from eight different disease categories were analyzed in four non-standardized and two standardized iSYS assays. There were strong correlations between the four non-standardized and two standardized assays with Spearman's rank r values between 0.975 and 0.961 and four of the eight r values were >0.97. R(2) values for the eight best-fit linear regression equations ranging between 0.947 and 0.916. None of the slopes were found to be significantly different from one another. Bland-Altman plots showed that the bias was comparable when each of the four non-standardized assays was compared to either of the standardized assays. When the data were segregated in values between 6 and 49ng/mL (15-122nmol/L) or between 50 and 100ng/mL (125-250nmol/L) significant associations remained between results obtained with non-standardized and standardized calibrators regardless of the absolute value. When five recent DEQAS unknowns were analyzed in one non-standardized and one standardized assay the mean percent difference from the NIST target in values obtained using standardized vs. non-standardized calibrators were not significantly different. Finally, strong and statistically significant associations between the results were obtained using non-standardized and standardized assays for six of eight clinical conditions. The only exceptions were hypocalcemia and breast

  18. Induction of apoptosis and inhibition of prostate and breast cancer growth by BGP-15, a new calcipotriene-derived vitamin D3 analog.

    PubMed

    Berkovich, Liron; Ben-Shabat, Shimon; Sintov, Amnon C

    2010-07-01

    The role of vitamin D3 in cancer prevention and its potential as an anticancer therapeutic agent have been researched and are well established. However, the clinical use of the natural vitamin D3 metabolite, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3 or calcitriol] is limited by a possible cause of hypercalcemia and hypercalciuria. A new 24-chloro calcipotriene-based vitamin D3 analog (BGP-15) was synthesized and examined for antiproliferative activity in the androgen-dependent cell lines of prostate cancer (LNCaP) and breast cancer (MCF-7). The new analog led to significant decrease in cell viability in cultured LNCaP and MCF-7 cell lines compared with calcipotriene and 1,25(OH)2D3. We observed elevated vitamin D receptor protein levels in both LNCaP and MCF-7 cells, which were treated with 5 micromol/l of 1,25(OH)2D3, calcipotriene or BGP-15 for 20 h, indicating vitamin D receptor-binding ability. Treatments of LNCaP and MCF-7 cells with 5 micromol/l BGP-15 and calcipotriene for 20 h generated procaspase-3 cleavage and therefore, apoptosis. Interestingly, BGP-15, and to a lesser extent calcipotriene, but not 1,25(OH)2D3, activated caspase-3 in MCF-7 cells, a cell line that normally lacks this specific caspase (and procaspase). It is presumed that management of MCF-7 with BGP-15 modulates procaspase-3 expression and cleavage, and a subsequent activation of caspase-3. Similar treatments of LNCaP cells induced procaspase-9 cleavage and therefore caspase-9 activation, whereas similar treatments of MCF-7 cells failed to induce caspase-9 activation. Cytochrome c release was, however, detected in both cell lines, LNCaP and MCF-7. In-vivo results suggested that BGP-15 (similar to its parent drug) did not cause calcium-related toxic side effects after chronic treatment.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. Vitamin D3 pretreatment regulates renal inflammatory responses during lipopolysaccharide-induced acute kidney injury.

    PubMed

    Xu, Shen; Chen, Yuan-Hua; Tan, Zhu-Xia; Xie, Dong-Dong; Zhang, Cheng; Zhang, Zhi-Hui; Wang, Hua; Zhao, Hui; Yu, De-Xin; Xu, De-Xiang

    2015-01-01

    Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury. PMID:26691774

  1. Effect of vitamin D3 on lifespan in Caenorhabditis elegans.

    PubMed

    Messing, Jennifer A; Heuberger, Roschelle; Schisa, Jennifer A

    2013-12-01

    Vitamin D is an essential micronutrient, necessary for human health. To determine if Caenorhabditis elegans (C. elegans) could function as an effective model to study the mechanisms of action of vitamin D, we asked if vitamin D3 affects C. elegans lifespan. Multiple factors positively impact lifespan in this system including dietary restriction and vitamin E. In addition, the C. elegans DAF-12 nuclear hormone receptor is homologous to the vitamin D receptor in humans and is therefore a candidate for a functional vitamin D receptor. It was hypothesized that vitamin D3 supplementation would increase the lifespan of C. elegans in a DAF-12-dependent manner. Dose-response curves were completed, and results indicate that exposure to 1,000 µg/ml vitamin D3 significantly increased the lifespan of wild-type worms by up to 39% (p<0.001). The daf-12 mutants exposed to 1,000 µg/ml vitamin D3 lived significantly longer than daf-12 controls exposed to 0 µg/ml (p<0.001), but among worms exposed to 1,000 µg/ml vitamin D3, wild type lived significantly longer than daf-12 (p<0.01). The data suggest that vitamin D3 can interact with multiple receptors, possibly implicating the NHR family of nuclear hormone receptors related to DAF-12. This research is the first to our knowledge to utilize C. elegans as a model to study the impact of vitamin D3 on longevity and supports the use of this model system to increase our understanding of vitamin D function at the cellular level, its role in cellular health, and its potential medicinal utility in humans.

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

    PubMed

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

    2013-08-01

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

  3. Determinants of Vitamin D Levels in Italian Children and Adolescents: A Longitudinal Evaluation of Cholecalciferol Supplementation versus the Improvement of Factors Influencing 25(OH)D Status.

    PubMed

    Stagi, Stefano; Pelosi, Paola; Strano, Massimo; Poggi, Giovanni; Manoni, Cristina; de Martino, Maurizio; Seminara, Salvatore

    2014-01-01

    Objective. This paper aims to assess 25(OH)D levels in Italian children and adolescents identifying risk factors for 25(OH)D deficiency and to evaluate whether a normal 25(OH)D value can be restored in 25(OH)D-deficient patients. Methods. We evaluated 25(OH)D levels in 679 Italian children and adolescents (≤10, 11-20, 21-30, and >30 ng/mL were defined as severe deficiency, deficiency, insufficiency, and sufficiency, resp.). Of these, 365 25(OH)D-deficient were followed up for 1 year; 205 were treated with cholecalciferol (Arm A: 400 I.U.) and 160 by improving the environmental variables influencing 25(OH)D levels (Arm B). Results. At cross-sectional evaluation, 11.3% showed sufficiency, 30.0% insufficiency, and 58.7% 25(OH)D deficiency. Mean 25(OH)D was 19.08 ± 8.44 ng/mL. At the enrollment time (T 0), no difference was found between Arms A and B with respect to distribution and 25(OH)D levels. At end time (T 1) 26.0% (29.7% in Arm A versus 20.6% in Arm B) showed sufficiency, 38.4% (42.0% versus 34.4%) insufficiency, and 35.6% (28.3% versus 45.0%) 25(OH)D deficiency. Mean 25(OH)D level was 23.71 ± 6.83 ng/mL. Conclusions. Neither changes of lifestyle nor 400 I.U. cholecalciferol supplementation alone appears to be sufficient to restore adequate 25(OH)D levels.

  4. The effect of 14 weeks of vitamin D3 supplementation on antimicrobial peptides and proteins in athletes.

    PubMed

    He, Cheng-Shiun; Fraser, William D; Tang, Jonathan; Brown, Kirsty; Renwick, Stephen; Rudland-Thomas, Jay; Teah, James; Tanqueray, Ellie; Gleeson, Michael

    2016-01-01

    Heavy training is associated with increased respiratory infection risk and antimicrobial proteins are important in defence against oral and respiratory tract infections. We examined the effect of 14 weeks of vitamin D3 supplementation (5000 IU/day) on the resting plasma cathelicidin concentration and the salivary secretion rates of secretory immunoglobulin A (SIgA), cathelicidin, lactoferrin and lysozyme in athletes during a winter training period. Blood and saliva were obtained at the start of the study from 39 healthy men who were randomly allocated to vitamin D3 supplement or placebo. Blood samples were also collected at the end of the study; saliva samples were collected after 7 and 14 weeks. Plasma total 25(OH)D concentration increased by 130% in the vitamin D3 group and decreased by 43% in the placebo group (both P = 0.001). The percentage change of plasma cathelicidin concentration in the vitamin D3 group was higher than in the placebo group (P = 0.025). Only in the vitamin D3 group, the saliva SIgA and cathelicidin secretion rates increased over time (both P = 0.03). A daily 5000 IU vitamin D3 supplement has a beneficial effect in up-regulating the expression of SIgA and cathelicidin in athletes during a winter training period, which could improve resistance to respiratory infections.

  5. Serum level of vitamin D3 in cutaneous melanoma

    PubMed Central

    de Oliveira, Renato Santos; de Oliveira, Daniel Arcuschin; Martinho, Vitor Augusto Melão; Antoneli, Célia Beatriz Gianotti; Marcussi, Ludmilla Altino de Lima; Ferreira, Carlos Eduardo dos Santos

    2014-01-01

    Objective To compare the level of vitamin D3 in cutaneous melanoma patients, with or without disease activity, with reference values and with patients from a general hospital. Methods The serum levels of vitamin D3 were measured in cutaneous melanoma patients, aged 20 to 88 years, both genders, from January 2010 to December 2013. The samples from the general group were processed at Hospital Israelita Albert Einstein (control group). Data analysis was performed using the Statistics software. Results A total of 100 patients were studied, 54 of them men, with mean age of 54.67 years, and 95 Caucasian. Out of these 100 patients, 17 had active disease. The average levels of vitamin D3 in the melanoma patients were lower than the level considered sufficient, but above the average of the control group. Both groups (with or without active disease) of patients showed a similar distribution of vitamin D3 deficiency. Conclusion Vitamin D3 levels in melanoma patients were higher than those of general patients and lower than the reference level. If the reference values are appropriate, a large part of the population had insufficient levels of vitamin D, including those with melanoma, or else, this standard needs to be reevaluated. No difference in vitamin D3 levels was found among melanoma patients with or without active disease. More comprehensive research is needed to assess the relation between vitamin D and melanoma. PMID:25628199

  6. Relationship between Body Mass Composition, Bone Mineral Density, Skin Fibrosis and 25(OH) Vitamin D Serum Levels in Systemic Sclerosis.

    PubMed

    Corrado, Addolorata; Colia, Ripalta; Mele, Angiola; Di Bello, Valeria; Trotta, Antonello; Neve, Anna; Cantatore, Francesco Paolo

    2015-01-01

    A reduced bone mineral density (BMD) is observed in several rheumatic autoimmune diseases, including Systemic Sclerosis (SSc); nevertheless, data concerning the possible determinants of bone loss in this disease are not fully investigated. The aim of this study is to evaluate the relationship between BMD, body mass composition, skin sclerosis and serum Vitamin D levels in two subsets of SSc patients. 64 post-menopausal SSc patients, classified as limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc, were studied. As control, 35 healthy post-menopausal women were recruited. Clinical parameters were evaluated, including the extent of skin involvement. BMD at lumbar spine, hip, femoral neck and body mass composition were determined by dual-energy X-ray absorptiometry. Serum calcium, phosphorus, alkaline phosphatase, urine pyridinium cross-links, intact parathyroid hormone and 25-hydroxyvitamin D (25OHD) were measured. BMD at spine, femoral neck and total hip was significantly lower in SSc patients compared to controls. In dcSSc subset, BMD at spine, femoral neck and total hip was significantly lower compared to lcSSc. No differences in both fat and lean mass were found in the three study groups even if patients with dcSSc showed a slightly lower total body mass compared to healthy controls. Total mineral content was significantly reduced in dSSc compared to both healthy subjects and lcSSc group. Hypovitaminosis D was observed both in healthy post-menopausal women and in SSc patients, but 25OHD levels were significantly lower in dcSSc compared to lcSSc and inversely correlated with the extent of skin thickness. These results support the hypothesis that the extent of skin involvement in SSc patients could be an important factor in determining low circulating levels of 25OHD, which in turn could play a significant role in the reduction of BMD and total mineral content. PMID:26375284

  7. Relationship between Body Mass Composition, Bone Mineral Density, Skin Fibrosis and 25(OH) Vitamin D Serum Levels in Systemic Sclerosis

    PubMed Central

    Corrado, Addolorata; Colia, Ripalta; Mele, Angiola; Di Bello, Valeria; Trotta, Antonello; Neve, Anna; Cantatore, Francesco Paolo

    2015-01-01

    A reduced bone mineral density (BMD) is observed in several rheumatic autoimmune diseases, including Systemic Sclerosis (SSc); nevertheless, data concerning the possible determinants of bone loss in this disease are not fully investigated. The aim of this study is to evaluate the relationship between BMD, body mass composition, skin sclerosis and serum Vitamin D levels in two subsets of SSc patients. 64 post-menopausal SSc patients, classified as limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc, were studied. As control, 35 healthy post-menopausal women were recruited. Clinical parameters were evaluated, including the extent of skin involvement. BMD at lumbar spine, hip, femoral neck and body mass composition were determined by dual-energy X-ray absorptiometry. Serum calcium, phosphorus, alkaline phosphatase, urine pyridinium cross-links, intact parathyroid hormone and 25-hydroxyvitamin D (25OHD) were measured. BMD at spine, femoral neck and total hip was significantly lower in SSc patients compared to controls. In dcSSc subset, BMD at spine, femoral neck and total hip was significantly lower compared to lcSSc. No differences in both fat and lean mass were found in the three study groups even if patients with dcSSc showed a slightly lower total body mass compared to healthy controls. Total mineral content was significantly reduced in dSSc compared to both healthy subjects and lcSSc group. Hypovitaminosis D was observed both in healthy post-menopausal women and in SSc patients, but 25OHD levels were significantly lower in dcSSc compared to lcSSc and inversely correlated with the extent of skin thickness. These results support the hypothesis that the extent of skin involvement in SSc patients could be an important factor in determining low circulating levels of 25OHD, which in turn could play a significant role in the reduction of BMD and total mineral content. PMID:26375284

  8. Circadian rhythm of serum 25 (OH) vitamin D, calcium and phosphorus levels in the treatment and management of type-2 diabetic patients.

    PubMed

    Masood, Tariq; Kushwaha, Rajeev S; Singh, Ranjana; Sailwal, Shivani; Pandey, Himanshu; Varma, Amit; Singh, Raj K; Cornelissen, Germaine

    2015-02-01

    The circadian time structure of serum 25 (OH) vitamin D (25-OHD), calcium (Ca) and phosphorus (P) may prove to be helpful in prevention, efficacy and management of diabetes mellitus. Ten newly diagnosed patients with type-2 diabetes mellitus (6 men and 4 women), 30-65 years of age, and 10 age-matched clinically healthy volunteers (7 men and 3 women) were synchronized for one week with diurnal activity from about 06:00 to about 22:00 and nocturnal rest. Breakfast was served around 08:00, lunch around 13:30 and dinner around 20:00. Drugs/nutraceuticals known to affect the vitamin D-calcium metabolism and status were not taken. Blood samples were collected at 6-h intervals for 24 h under standardized, 24-h synchronized conditions. Serum 25-OHD, Ca, P, Ca-P product and Ca-P ratio were determined. A marked circadian variation was demonstrated for 25-OHD in healthy volunteers (p = 0.030) and of borderline statistical significance in the diabetic patients (p = 0.083) by population-mean cosinor analysis. Similarly, healthy volunteers showed borderline significance for serum Ca, P and Ca-P ratio. The circadian acrophase of Ca occurred later in the patients as compared to healthy controls. Mapping the circadian rhythm (an important component of the broader time structure or chronome, which includes a.o., trends with age and extra-circadian components) of vitamin D and calcium is needed for exploring their role as markers in the treatment and management of diabetic patients. PMID:25788054

  9. High-Dose Vitamin D3 Supplementation in Children and Young Adults with HIV: A Randomized, Placebo-Controlled Trial

    PubMed Central

    Stallings, Virginia A.; Schall, Joan I.; Hediger, Mary L.; Zemel, Babette S.; Tuluc, Florin; Dougherty, Kelly A.; Samuel, Julia L.; Rutstein, Richard M.

    2014-01-01

    Background Suboptimal vitamin D status is prevalent in HIV-infected patients and associated with increased risk of disease severity and morbidity. We aimed to determine 12-mo safety and efficacy of daily 7000IU vitamin D3 (vitD3) vs placebo to sustain increased serum 25-hydroxyvitamin D (25(OH)D) and improve immune status in HIV-infected subjects. Methods This was a double-blind trial of perinatally- (PHIV) or behaviorally-acquired (BHIV) HIV-infected subjects (5.0–24.9y). Safety, 25(OH)D-related parameters, and immune status were assessed at baseline, 3, 6, and 12 months. Results Fifty-eight subjects enrolled (67% male, 85% African-American, 64% BHIV) and 50 completed with no safety concerns. In unadjusted analyses, there were no differences between randomization groups at baseline; at 3, 6, and 12 months, 25(OH)D was higher with supplementation than baseline and higher than with placebo (P<0.05). In adjusted mixed models, in the supplementation group, the fixed effect of 25(OH)D was higher (P<0.001). Percentage of naïve T helper cells (Th naïve%) were significantly (P<0.01) and T helper cells (CD4%) marginally (P<0.10) increased with supplementation in those taking highly active antiretroviral therapy (HAART), and RNA viral load was reduced (P ≤ 0.05). In exploratory linear models, change in 25(OH)D predicted RNA viral load at 3 and 12 months and CD4% at 3 months (P<0.05). Conclusions Daily 7000IU vitD3 for 12 months was safe in HIV-infected subjects and effective in increasing 25(OH)D. Supplementation improved in some clinically important HIV immune markers in subjects on HAART. Adjunct therapy with high-dose, daily vitD3 for HIV-infected subjects and for those on/off HAART requires further investigation. PMID:24988118

  10. Developmental Vitamin D3 deficiency alters the adult rat brain.

    PubMed

    Féron, F; Burne, T H J; Brown, J; Smith, E; McGrath, J J; Mackay-Sim, A; Eyles, D W

    2005-03-15

    There is growing evidence that Vitamin D(3) (1,25-dihydroxyvitamin D(3)) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D(3) deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The aim of the current study was to examine if there were any permanent outcomes into adulthood when the offspring of Vitamin D(3) deficient dams were restored to a normal diet. The brains of adult rats were examined at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning. Compared to controls animals that were exposed to transient early Vitamin D(3) deficiency had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). We conclude that transient early life hypovitaminosis D(3) not only disrupts brain development but leads to persistent changes in the adult brain. In light of the high incidence of hypovitaminosis D(3) in women of child-bearing age, the public health implications of these findings warrant attention. PMID:15763180

  11. Effect of dietary calcium and 1,25-(OH)2D3 on the expression of calcium transport genes in calbindin-D9k and -D28k double knockout mice.

    PubMed

    Ko, Sang-Hwan; Choi, Kyung-Chul; Oh, Goo Taeg; Jeung, Eui-Bae

    2009-02-01

    The phenotypes of calbindin-D9k (CaBP-9k) and -28k (CaBP-28k) single knockout (KO) mice are similar to wild-type (WT) mice due to the compensatory action of other calcium transport proteins. In this study, we generated CaBP-9k/CaBP-28k double knockout (DKO) mice in order to investigate the importance of CaBP-9k and CaBP-28k in active calcium processing. Under normal dietary conditions, DKO mice did not exhibit any changes in phenotype or the expression of active calcium transport genes as compared to WT or CaBP-28k KO mice. Under calcium-deficient dietary conditions, the phenotype and expression of calcium transport genes in CaBP-28k KO mice were similar to WT, whereas in DKO mice, serum calcium levels and bone length were decreased. The intestinal and renal expression of transient receptor potential vanilloid member 6 (TRPV6) mRNA was significantly decreased in DKO mice fed a calcium-deficient diet as compared to CaBP-28k KO or WT mice, and DKO mice died after 4 weeks on a calcium-deficient diet. Body weight, bone mineral density (BMD) and bone length were significantly reduced in all mice fed a calcium and 1,25-(OH)(2)D(3)-deficient diet, as compared to a normal diet, and none of the mice survived more than 4 weeks. These results indicate that deletion of CaBP-28k alone does not affect body calcium homeostasis, but that deletion of CaBP-9k and CaBP-28k has a significant effect on calcium processing under calcium-deficient conditions, confirming the importance of dietary calcium and 1,25-(OH)(2)D(3) during growth and development.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  14. Regulation of human tonsillar T-cell proliferation by the active metabolite of vitamin D3.

    PubMed Central

    Nunn, J D; Katz, D R; Barker, S; Fraher, L J; Hewison, M; Hendy, G N; O'Riordan, J L

    1986-01-01

    We have examined the effects of 1,25(OH)2D3 on T-cell populations isolated by buoyant density and E rosetting from human tonsils. Cell proliferation was assessed by measuring the incorporation of 125iododeoxyuridine; interleukin-2 (IL-2) production was measured using an IL-2-dependent cell line, and the number of 1,25(OH)2D3 receptors was measured by whole-cell nuclear association assay. At a concentration of 10(-7) M, 1,25(OH)2D3 inhibited mitogen-induced T-cell proliferation in all E+ T-cell populations. This effect was more pronounced in the cells from the intermediate and high density layers and was reflected both in cell proliferative responses and in relative IL-2 synthesis. By adding the 1,25(OH)2D3 during the course of the mitogen assay, we demonstrated that activation of the T cell precedes the 1,25(OH)2D3-mediated inhibition. Cells that had been preincubated with mitogen in the presence of the 1,25(OH)2D3 were refractory to further stimulation by mitogens. Receptors for 1,25(OH)2D3 could not be detected in unstimulated T cells. However, activation led to the expression of high-affinity receptors for 1,25(OH)2D3. Co-incubation of the cells with mitogen and 1,25(OH)2D3 increased the number of receptors compared with mitogen alone. The effects provide further evidence for the hypothesis that 1,25(OH)2D3 is an important potential modulator of the immune system through its action on T cells. Taking our observations in conjunction with the known capacity of monocytes to hydroxylate the precursor metabolite (and thus synthesize the active form of cholecalciferol), the results support the suggestion that 1,25(OH)2D3 plays a role as a local mediator of mononuclear phagocyte-T cell interaction in human lymphomedullary tissues. PMID:3026959

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

    SciTech Connect

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

    1985-03-01

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

  16. Influence of Vitamin D Status and Vitamin D3 Supplementation on Genome Wide Expression of White Blood Cells: A Randomized Double-Blind Clinical Trial

    PubMed Central

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

    2013-01-01

    Background Although there have been numerous observations of vitamin D deficiency and its links to chronic diseases, no studies have reported on how vitamin D status and vitamin D3 supplementation affects broad gene expression in humans. The objective of this study was to determine the effect of vitamin D status and subsequent vitamin D supplementation on broad gene expression in healthy adults. (Trial registration: ClinicalTrials.gov NCT01696409). Methods and Findings A randomized, double-blind, single center pilot trial was conducted for comparing vitamin D supplementation with either 400 IUs (n = 3) or 2000 IUs (n = 5) vitamin D3 daily for 2 months on broad gene expression in the white blood cells collected from 8 healthy adults in the winter. Microarrays of the 16 buffy coats from eight subjects passed the quality control filters and normalized with the RMA method. Vitamin D3 supplementation that improved serum 25-hydroxyvitamin D concentrations was associated with at least a 1.5 fold alteration in the expression of 291 genes. There was a significant difference in the expression of 66 genes between subjects at baseline with vitamin D deficiency (25(OH)D<20 ng/ml) and subjects with a 25(OH)D>20 ng/ml. After vitamin D3 supplementation gene expression of these 66 genes was similar for both groups. Seventeen vitamin D-regulated genes with new candidate vitamin D response elements including TRIM27, CD83, COPB2, YRNA and CETN3 which have been shown to be important for transcriptional regulation, immune function, response to stress and DNA repair were identified. Conclusion/Significance Our data suggest that any improvement in vitamin D status will significantly affect expression of genes that have a wide variety of biologic functions of more than 160 pathways linked to cancer, autoimmune disorders and cardiovascular disease with have been associated with vitamin D deficiency. This study reveals for the first time molecular finger prints that help explain the

  17. Hepatocellular carcinoma cells express 25(OH)D-1α-hydroxylase and are able to convert 25(OH)D to 1α,25(OH)₂D, leading to the 25(OH)D-induced growth inhibition.

    PubMed

    Chiang, Kun-Chun; Yen, Cho-Li; Yeh, Chun-Nan; Hsu, Jun-Te; Chen, Li-Wei; Kuo, Sheng-Fong; Wang, Shang-Yu; Sun, Chi-Chin; Kittaka, Atsushi; Chen, Tai C; Yeh, Ta-Sen; Hsu, Shu-Yuan; Juang, Horng-Heng

    2015-11-01

    Hepatocellular carcinoma (HCC) is the most diagnosed liver cancer without effective treatments available for advanced HCC. Vitamin D is getting popular due to its anti-cancer characteristics. However, the clinical application of 1α,25(OH)2D, the active form of vitamin, is hampered by its hypercalcemia side effect. 1α,25(OH)2D is converted from 25(OH)D, the index of serum vitamin D status, by CYP27B1, which is originally found in kidneys but recently detected in non-renal tissues. 25(OH)D has been shown to repress some cancers expressing CYP27B1 due to the local conversion of 25(OH)D to 1α,25(OH)2D, which works in a intra-, auto-, or paracrine manner and thus minimizes the risk of hypercalcemia. In this study, we found CYP27B1 expression in human hepatocyte, HCC, and HepG2 cells. As we treated HepG2 cells with 25(OH)D, the 1α,25(OH)2D target gene CYP24A1 expression was increased and was further upregulated as CYP27B1 transfection or downregulated as CYP27B1 knockdown. Other 1α,25(OH)2D target genes in HepG2 cells, p21 and p27 were also stimulated by 25(OH)D after CYP27B1 transfection. Further, 25(OH)D could inhibit HepG2 cells growth, which was potentiated by CYP27B1 transfection. Collectively, we showed for the first time that HCC expressed CYP27B1 and was able to covert 25(OH)D to 1α,25(OH)2D in vitro, thus responsive to 25(OH)D treatment. Our data justifies the application of 25(OH)D and CYP27B1 gene transfection therapy in further HCC treatment studies.

  18. Changes in the vitamin D endocrine system and bone turnover after oral vitamin D3 supplementation in healthy adults: results of a randomised trial

    PubMed Central

    2012-01-01

    Background There is uncertainty as to which intake of vitamin D is needed to suppress PTH and maintain normal bone metabolism throughout winter at northern latitudes. We aimed to investigate whether four weeks’ daily supplementation with 10 μg vitamin D3 from fish oil produced a greater change in serum vitamin D metabolites, parathyroid hormone, and bone turnover in healthy adults compared with solid multivitamin tablets. Furthermore, it was studied whether age, gender, ethnic background, body mass index, or serum concentrations at baseline predicted the magnitude of change in these parameters. Methods Healthy adults aged 19–48 years living in Oslo, Norway (59°N) were randomised to receive a daily dose of 10 μg vitamin D3 given as fish oil capsules or multivitamin tablets during four weeks in late winter. Serum samples from baseline and after 28 days were analysed for 25-hydroxyvitamin D (s-25(OH)D), 1,25-dihydroxyvitamin D (s-1,25(OH)2D), intact parathyroid hormone (s-iPTH), and osteoclast-specific tartrate-resistant acid phosphatase 5b (s-TRACP). Fifty-five eligible participants completed the intervention (74% of those randomised). Results S-25(OH)D increased by mean 34.1 (SD 13.1) nmol/l, p < 0.001; s-iPTH decreased by mean 1.2 (SD 2.5) pmol/l, p = 0.001; s-1,25(OH)2D increased by mean 13 (SD 48) pmol/l, p = 0.057; and s-TRACP increased by mean 0.38 (SD 0.33) U/l, p < 0.001. For all these parameters, there was no difference between fish oil and multivitamin formulation. Baseline concentrations were the only independent predictors of changes in biochemical parameters. Conclusions Four weeks of daily supplementation with 10 μg vitamin D3 decreased mean s-iPTH and increased s-TRACP concentration, and this did not differ by mode of administration. Our results suggest an increased bone resorption following vitamin D supplementation in young individuals, despite a decrease in parathyroid hormone levels. Trial Registration Clinical

  19. Vitamin D3 and cardiovascular function in rats.

    PubMed Central

    Weishaar, R E; Simpson, R U

    1987-01-01

    We have previously identified a receptor for 1,25-dihydroxyvitamin D3 in myocardial cells (Simpson, R.U. 1983. Circulation. 68:239.). To establish the relevance of this observation, we evaluated the role of the prohormone vitamin D3 in regulating cardiovascular function. In rats maintained on a vitamin D3-deficient diet for nine weeks, increases in systolic blood pressure (BP) and serum creatine phosphokinase (CPK) were observed. These increases coincided with a reduction of serum calcium from 10.3 to 5.6 mg/dl. However, while serum calcium remained depressed throughout the study, increases in BP and serum CPK were transient. After nine weeks of vitamin D3-depletion, but not after six weeks, ventricular and vascular muscle contractile function were also markedly enhanced. The increase in ventricular contractile function could not be prevented by maintaining serum calcium at 9.0 mg/dl during the period of D3-depletion. These observations suggest a primary role for the vitamin D3-endocrine system in regulating cardiovascular function. PMID:3034981

  20. 1,25-Dihydroxyvitamin D3 Enhances Innate Immune Responses of Bovine Mammary Epithelial Cells that are Triggered by Toll-like Receptor Signaling

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  1. 21 CFR 172.380 - Vitamin D3.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the... crystallization. (b) Vitamin D3 meets the specifications of the Food Chemicals Codex, 5th ed. (2004), pp....

  2. 21 CFR 172.380 - Vitamin D 3;.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the... crystallization. (b) Vitamin D3 meets the specifications of the Food Chemicals Codex, 5th ed. (2004), pp....

  3. 21 CFR 172.380 - Vitamin D 3.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the United States Pharmacopeial.../federal-register/cfr/ibr-locations.html. (c) The additive may be used as follows: (1) At levels not to...-dehydrocholesterol produced from cholesterol and is purified by crystallization. (b) Vitamin D3 meets...

  4. 21 CFR 172.380 - Vitamin D3.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the... crystallization. (b) Vitamin D3 meets the specifications of the Food Chemicals Codex, 5th ed. (2004), pp....

  5. 21 CFR 172.380 - Vitamin D3.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the... crystallization. (b) Vitamin D3 meets the specifications of the Food Chemicals Codex, 5th ed. (2004), pp....

  6. 25(OH)D Is Effective to Repress Human Cholangiocarcinoma Cell Growth through the Conversion of 25(OH)D to 1α,25(OH)₂D₃.

    PubMed

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

    2016-01-01

    Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1α,25(OH)₂D₃, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1α,25(OH)₂D₃, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1α,25(OH)₂D₃ has been found in some cancer cells with CYP27B1 expression. In this study, CYP27B1 expression was demonstrated in CCA cells and human CCA specimens. 25(OH)D effectively represses SNU308 cells growth, which was strengthened or attenuated as CYP27B1 overexpression or knockdown. Lipocalcin-2 (LCN2) was also found to be repressed by 25(OH)D. After treatment with 800 ng/mL 25(OH)D, the intracellular 1α,25(OH)₂D₃ concentration was higher in SNU308 cells with CYP27B1 overexpression than wild type SNU308 cells. In a xenograft animal experiment, 25(OH)D, at a dose of 6 μg/kg or 20 μg/kg, significantly inhibited SNU308 cells' growth without inducing obvious side effects. Collectively, our results indicated that SNU308 cells were able to convert 25(OH)D to 1α,25(OH)₂D₃ and 25(OH)D CYP27B1 gene therapy could be deemed as a promising therapeutic direction for CCA. PMID:27529229

  7. Vitamin D(3) receptor ablation alters mammary gland morphogenesis.

    PubMed

    Zinser, Glendon; Packman, Kathryn; Welsh, JoEllen

    2002-07-01

    Postnatal mammary gland morphogenesis is achieved through coordination of signaling networks in both the epithelial and stromal cells of the developing gland. While the major proliferative hormones driving pubertal mammary gland development are estrogen and progesterone, studies in transgenic and knockout mice have successfully identified other steroid and peptide hormones that impact on mammary gland development. The vitamin D(3) receptor (VDR), whose ligand 1,25-dihydroxyvitamin D(3) is the biologically active form of vitamin D(3), has been implicated in control of differentiation, cell cycle and apoptosis of mammary cells in culture, but little is known about the physiological relevance of the vitamin D(3) endocrine system in the developing gland. In these studies, we report the expression of the VDR in epithelial cells of the terminal end bud and subtending ducts, in stromal cells and in a subset of lymphocytes within the lymph node. In the terminal end bud, a distinct gradient of VDR expression is observed, with weak VDR staining in proliferative populations and strong VDR staining in differentiated populations. The role of the VDR in ductal morphogenesis was examined in Vdr knockout mice fed high dietary Ca(2+) which normalizes fertility, serum estrogen and neonatal growth. Our results indicate that mammary glands from virgin Vdr knockout mice are heavier and exhibit enhanced growth, as evidenced by higher numbers of terminal end buds, greater ductal outgrowth and enhanced secondary branch points, compared with glands from age- and weight-matched wild-type mice. In addition, glands from Vdr knockout mice exhibit enhanced growth in response to exogenous estrogen and progesterone, both in vivo and in organ culture, compared with glands from wild-type mice. Our data provide the first in vivo evidence that 1,25-dihydroxyvitamin D(3) and the VDR impact on ductal elongation and branching morphogenesis during pubertal development of the mammary gland. Collectively

  8. Randomized placebo-controlled trial of high-dose prenatal third-trimester vitamin D3 supplementation in Bangladesh: the AViDD trial

    PubMed Central

    2013-01-01

    Background Antenatal vitamin D status may be associated with the risk of adverse pregnancy and neonatal outcomes; however, the benefits of vitamin D supplementation during pregnancy remain unknown. Methods We conducted a double-blind placebo-controlled randomized trial to evaluate the effect of high-dose prenatal 3rd trimester vitamin D3 supplementation on maternal and neonatal (cord blood) serum 25-hydroxyvitamin D (25(OH)D) concentration (primary biochemical efficacy outcome) and maternal serum calcium concentration (primary safety measure). Eligibility criteria were pregnant women aged 18 to <35 years, at 26 to 29 weeks gestation, and residing in Dhaka, Bangladesh. 160 women were randomized by 1:1 allocation to one of two parallel intervention groups; placebo (n = 80) or 35,000 IU/week of vitamin D3 (n = 80) until delivery. All participants, study personnel and study investigators were blind to treatment allocation. Results Mean maternal 25(OH)D concentration was similar in the vitamin D and placebo groups at baseline (45 vs. 44 nmol/L; p = 0.66), but was significantly higher in the vitamin D group vs. placebo group among mothers at delivery (134 vs. 38 nmol/L; p < 0.001) and newborns (cord blood: 103 vs. 39; p < 0.001). In the vitamin D group, 95% of neonates and 100% of mothers attained 25(OH)D >50 nmol/L, versus 21% mothers and 19% of neonates in the placebo group. No participants met criteria for hypercalcemia, there were no known supplement-related adverse events, and major pregnancy outcomes were similar between groups. Conclusions Antenatal 3rd-trimester vitamin D3 supplementation (35,000 IU/week) significantly raised maternal and cord serum 25(OH)D concentrations above 50 nmol/L in almost all participants without inducing hypercalcemia or other observed safety concerns. Doses up to 35,000 IU/week may be cautiously used in further research aimed at establishing the clinical effects and safety of vitamin D3 supplementation in

  9. 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

    PubMed Central

    van Amerongen, Barbara M.; Feron, François

    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 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(OH)2D 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(OH)D, PTH, Ca levels, UCa/Cr and bone health become part of the integral management of persons with MS. PMID:23202962

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

    PubMed

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

    2004-11-01

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

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

    PubMed Central

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

    2012-01-01

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

  12. Effect of 12-Week Vitamin D Supplementation on 25[OH]D Status and Performance in Athletes with a Spinal Cord Injury.

    PubMed

    Flueck, Joelle Leonie; Schlaepfer, Max Walter; Perret, Claudio

    2016-09-22

    (1) BACKGROUND: studies with able-bodied athletes showed that performance might possibly be influenced by vitamin D status. Vitamin D seems to have a direct impact on neuromuscular function by docking on vitamin D receptors in the muscle tissue. Additionally, a high prevalence of vitamin D deficiency was shown not only in infants and in the elderly but also in healthy adults and spinal cord injured individuals. Therefore, the aim of our study was to investigate whether a vitamin D dose of 6000 IU daily over 12 weeks would be sufficient to increase vitamin D status in indoor wheelchair athletes to a normal or optimal vitamin D level and whether vitamin D deficiency is associated with an impairment in muscle performance in these individuals; (2) METHODS: vitamin D status was assessed in indoor elite wheelchair athletes in order to have a baseline measurement. If vitamin D status was below 75 nmol/L, athletes were supplemented with 6000 IU of vitamin D daily over 12 weeks. A vitamin D status over 75 nmol/L was supplemented with a placebo supplement. Vitamin D status, as well as a Wingate test and an isokinetic dynamometer test, were performed at baseline and after six and 12 weeks; (3) RESULTS: 20 indoor elite wheelchair athletes participated in this double-blind study. All of these athletes showed an insufficient vitamin D status at baseline and were, therefore, supplemented with vitamin D. All athletes increased vitamin D status significantly over 12 weeks and reached an optimal level. Wingate performance was not significantly increased. Isokinetic dynamometer strength was significantly increased but only in the non-dominant arm in isometric and concentric elbow flexion; (4) CONCLUSION: a dose of 6000 IU of vitamin D daily over a duration of 12 weeks seems to be sufficient to increase vitamin D status to an optimal level in indoor wheelchair athletes. It remains unclear, whether upper body performance or muscle strength and vitamin D status are associated with each

  13. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats.

    PubMed

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

    2016-01-01

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

  14. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats

    PubMed Central

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

    2016-01-01

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

  15. Vitamin D expenditure is not altered in pregnancy and lactation despite changes in vitamin D metabolite concentrations

    PubMed Central

    Jones, Kerry S; Assar, Shima; Prentice, Ann; Schoenmakers, Inez

    2016-01-01

    Pregnancy and lactation are associated with changes in vitamin D and calcium metabolism but the impact of these changes on vitamin D expenditure is unknown. We measured plasma 25(OH)D3 half-life with a stable-isotope tracer and investigated relationships with vitamin D metabolites in pregnant, lactating and ‘non-pregnant, non-lactating’ (NPNL) women. Vitamin D metabolites, vitamin D binding protein (DBP), PTH and 25(OH)D3 half-life were measured in third-trimester pregnant women (n22) and repeated during lactation 12 weeks post-partum (n14) and twice in NPNL women (n23 and n10, respectively) in rural Gambia where calcium intakes are low with little seasonality in UVB-exposure. 25(OH)D3 half-life was not significantly different between groups (mean(SD): 20.6(6.8), 22.6(7.7), 18.0(4.7) and 17.7(9.5) days in pregnant, lactating and NPNL women, respectively). Plasma 25(OH)D3, 1,25(OH)2D, and DBP were higher in pregnancy, and calculated free-25(OH)D3 and PTH were lower (P < 0.05). In lactation, 25(OH)D3 and 24,25(OH)2D3 were lower compared to pregnant (P < 0.001, P = 0.02) and NPNL women (P = 0.04, P = 0.07). Significant associations were observed between half-life and 25(OH)D3 (+ve) in pregnancy, and in all groups between 25(OH)D3 and free-25(OH)D3 (+ve) and PTH and 25(OH)D3 (−ve) (P < 0.0001). These data suggest that adaptive changes in pregnancy and lactation occur that prevent pronounced changes in vitamin D expenditure. PMID:27222109

  16. Randomized, blinded trial of vitamin D3 for treating aromatase inhibitor-associated musculoskeletal symptoms (AIMSS).

    PubMed

    Shapiro, Alice C; Adlis, Susan A; Robien, Kim; Kirstein, Mark N; Liang, Shuang; Richter, Sara A; Lerner, Rachel E

    2016-02-01

    The purpose of the study was to evaluate the efficacy and safety of vitamin D3 at 4000 IU/day as a treatment option for aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) when compared with the usual care dose of 600 IU D3. We conducted a single site randomized, double-blind, phase 3 clinical trial in women with AIMSS comparing change in symptoms, reproductive hormones and AI pharmacokinetics. Postmenopausal women ≥18 years with stages I-IIIA breast cancer, taking AI and experiencing AIMSS [breast cancer prevention trial symptom scale-musculoskeletal (BCPT-MS) subscale ≥1.5] were admitted. Following randomization, 116 patients had a run-in period of 1 month on 600 IU D3, then began the randomized assignment to either 600 IU D3 (n = 56) or 4000 IU D3 (n = 57) daily for 6 months. The primary endpoint was a change in AIMSS from baseline (after 1 month run-in) on the BCPT-MS (general MS pain, joint pain, muscle stiffness, range for each question: 0 = not at all to 4 = extremely). Groups had no statistically significant differences demographically or clinically. There were no discernable differences between the randomly allocated treatment groups at 6 months in measures of AIMSS, pharmacokinetics of anastrozole and letrozole, serum levels of reproductive hormones, or adverse events. We found no significant changes in AIMSS measures between women who took 4000 IU D3 daily compared with 600 IU D3. The 4000 IU D3 did not adversely affect reproductive hormone levels or the steady state pharmacokinetics of anastrozole or letrozole. In both groups, serum 25(OH)D remained in the recommended range for bone health (≥30 ng/mL) and safety (<50 ng/mL). PMID:26868123

  17. Randomized, blinded trial of vitamin D3 for treating aromatase inhibitor-associated musculoskeletal symptoms (AIMSS).

    PubMed

    Shapiro, Alice C; Adlis, Susan A; Robien, Kim; Kirstein, Mark N; Liang, Shuang; Richter, Sara A; Lerner, Rachel E

    2016-02-01

    The purpose of the study was to evaluate the efficacy and safety of vitamin D3 at 4000 IU/day as a treatment option for aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) when compared with the usual care dose of 600 IU D3. We conducted a single site randomized, double-blind, phase 3 clinical trial in women with AIMSS comparing change in symptoms, reproductive hormones and AI pharmacokinetics. Postmenopausal women ≥18 years with stages I-IIIA breast cancer, taking AI and experiencing AIMSS [breast cancer prevention trial symptom scale-musculoskeletal (BCPT-MS) subscale ≥1.5] were admitted. Following randomization, 116 patients had a run-in period of 1 month on 600 IU D3, then began the randomized assignment to either 600 IU D3 (n = 56) or 4000 IU D3 (n = 57) daily for 6 months. The primary endpoint was a change in AIMSS from baseline (after 1 month run-in) on the BCPT-MS (general MS pain, joint pain, muscle stiffness, range for each question: 0 = not at all to 4 = extremely). Groups had no statistically significant differences demographically or clinically. There were no discernable differences between the randomly allocated treatment groups at 6 months in measures of AIMSS, pharmacokinetics of anastrozole and letrozole, serum levels of reproductive hormones, or adverse events. We found no significant changes in AIMSS measures between women who took 4000 IU D3 daily compared with 600 IU D3. The 4000 IU D3 did not adversely affect reproductive hormone levels or the steady state pharmacokinetics of anastrozole or letrozole. In both groups, serum 25(OH)D remained in the recommended range for bone health (≥30 ng/mL) and safety (<50 ng/mL).

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

    MedlinePlus

    ... respiratory tract Share | Exposure to cigarette smoke reduces vitamin D3 in the blood stream and respiratory tract ... be understood as to how smoke causes inflammation. Vitamin D3 has anti-inflammatory and anti-bacterial effects. ...

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

    PubMed

    Coussens, Anna K; Wilkinson, Robert J; Martineau, Adrian R

    2015-07-01

    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(OH)D3 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(OH)D3 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(OH)D3 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(OH)D3 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. Effect of 12-Week Vitamin D Supplementation on 25[OH]D Status and Performance in Athletes with a Spinal Cord Injury.

    PubMed

    Flueck, Joelle Leonie; Schlaepfer, Max Walter; Perret, Claudio

    2016-01-01

    (1) BACKGROUND: studies with able-bodied athletes showed that performance might possibly be influenced by vitamin D status. Vitamin D seems to have a direct impact on neuromuscular function by docking on vitamin D receptors in the muscle tissue. Additionally, a high prevalence of vitamin D deficiency was shown not only in infants and in the elderly but also in healthy adults and spinal cord injured individuals. Therefore, the aim of our study was to investigate whether a vitamin D dose of 6000 IU daily over 12 weeks would be sufficient to increase vitamin D status in indoor wheelchair athletes to a normal or optimal vitamin D level and whether vitamin D deficiency is associated with an impairment in muscle performance in these individuals; (2) METHODS: vitamin D status was assessed in indoor elite wheelchair athletes in order to have a baseline measurement. If vitamin D status was below 75 nmol/L, athletes were supplemented with 6000 IU of vitamin D daily over 12 weeks. A vitamin D status over 75 nmol/L was supplemented with a placebo supplement. Vitamin D status, as well as a Wingate test and an isokinetic dynamometer test, were performed at baseline and after six and 12 weeks; (3) RESULTS: 20 indoor elite wheelchair athletes participated in this double-blind study. All of these athletes showed an insufficient vitamin D status at baseline and were, therefore, supplemented with vitamin D. All athletes increased vitamin D status significantly over 12 weeks and reached an optimal level. Wingate performance was not significantly increased. Isokinetic dynamometer strength was significantly increased but only in the non-dominant arm in isometric and concentric elbow flexion; (4) CONCLUSION: a dose of 6000 IU of vitamin D daily over a duration of 12 weeks seems to be sufficient to increase vitamin D status to an optimal level in indoor wheelchair athletes. It remains unclear, whether upper body performance or muscle strength and vitamin D status are associated with each

  1. Effect of 12-Week Vitamin D Supplementation on 25[OH]D Status and Performance in Athletes with a Spinal Cord Injury

    PubMed Central

    Flueck, Joelle Leonie; Schlaepfer, Max Walter; Perret, Claudio

    2016-01-01

    (1) Background: studies with able-bodied athletes showed that performance might possibly be influenced by vitamin D status. Vitamin D seems to have a direct impact on neuromuscular function by docking on vitamin D receptors in the muscle tissue. Additionally, a high prevalence of vitamin D deficiency was shown not only in infants and in the elderly but also in healthy adults and spinal cord injured individuals. Therefore, the aim of our study was to investigate whether a vitamin D dose of 6000 IU daily over 12 weeks would be sufficient to increase vitamin D status in indoor wheelchair athletes to a normal or optimal vitamin D level and whether vitamin D deficiency is associated with an impairment in muscle performance in these individuals; (2) Methods: vitamin D status was assessed in indoor elite wheelchair athletes in order to have a baseline measurement. If vitamin D status was below 75 nmol/L, athletes were supplemented with 6000 IU of vitamin D daily over 12 weeks. A vitamin D status over 75 nmol/L was supplemented with a placebo supplement. Vitamin D status, as well as a Wingate test and an isokinetic dynamometer test, were performed at baseline and after six and 12 weeks; (3) Results: 20 indoor elite wheelchair athletes participated in this double-blind study. All of these athletes showed an insufficient vitamin D status at baseline and were, therefore, supplemented with vitamin D. All athletes increased vitamin D status significantly over 12 weeks and reached an optimal level. Wingate performance was not significantly increased. Isokinetic dynamometer strength was significantly increased but only in the non-dominant arm in isometric and concentric elbow flexion; (4) Conclusion: a dose of 6000 IU of vitamin D daily over a duration of 12 weeks seems to be sufficient to increase vitamin D status to an optimal level in indoor wheelchair athletes. It remains unclear, whether upper body performance or muscle strength and vitamin D status are associated with each

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

    SciTech Connect

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

    1990-05-01

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

  3. Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis.

    PubMed

    Li, Mei; Hener, Pierre; Zhang, Zhikun; Kato, Shigeaki; Metzger, Daniel; Chambon, Pierre

    2006-08-01

    We have demonstrated that cytokine thymic stromal lymphopoietin (TSLP), whose expression is rapidly induced upon keratinocyte-selective ablation of retinoid X receptors (RXRs) -alpha and -beta in the mouse (RXRalphabeta(ep-/-) mice), plays a key role in initiating a skin and systemic atopic dermatitis-like phenotype. We show here that topical application of the physiologically active ligand [1alpha,25-(OH)(2)D(3); calcitriol] of the vitamin D receptor, or of its low-calcemic analog MC903 (calcipotriol; Dovonex), induces TSLP expression in epidermal keratinocytes, which results in an atopic dermatitis-like syndrome mimicking that seen in RXRalphabeta(ep-/-) mutants and transgenic mice overexpressing TSLP in keratinocytes. Furthermore, topical application of retinoic acid receptor RARgamma-selective agonist BMS961 also induces TSLP expression either on its own or synergistically with 1alpha,25-(OH)(2)D(3). Our data demonstrate that RXR/vitamin D receptor and RXR/retinoic acid receptor-gamma heterodimers and their ligands cell-autonomously control the expression of TSLP in epidermal keratinocytes of the mouse. We propose molecular mechanisms through which vitamin D3 and retinoic acid signalings could be involved in the pathogenesis of atopic diseases.

  4. Safety and Efficacy of High-Dose Daily Vitamin D3 Supplementation in Children and Young Adults Infected With Human Immunodeficiency Virus

    PubMed Central

    Dougherty, Kelly A.; Schall, Joan I.; Zemel, Babette S.; Tuluc, Florin; Hou, Xiaoling; Rutstein, Richard M.; Stallings, Virginia A.

    2014-01-01

    Background Suboptimal vitamin D (vitD) status is common in children and young adults infected with human immunodeficiency virus (HIV). The vitD supplemental dose needed to normalize vitD status in this population is unknown. Methods In this double-blind trial, subjects infected with HIV ages 8.3 to 24.9 years were randomized to vitD3 supplementation of 4000 IU/day or 7000 IU/day and evaluated at 6 and 12 week for changes in vitD status and HIV indicators. A dose was considered unsafe if serum calcium was elevated (above age and sex-specific range) associated with elevated serum 25 hydroxyvitamin D (25(OH)D); >160 ng/mL). Results At baseline, 95% of subjects (n = 44; 43% with perinatally acquired HIV, 57% with behaviorally acquired HIV) had a suboptimal serum 25(OH)D concentration of <32 ng/mL (mean ± standard deviation, 19.3 ± 7.4; range, 4.4–33.6 ng/mL). After 12 weeks (main outcome) of D3 supplementation, both D3 doses were safe and well tolerated, with no evidence of elevation of serum calcium concentrations or deterioration in HIV immunologic or virologic status. Sufficient vitD status, defined as serum 25(OH)D ≥32 ng/mL, was achieved in 81% of all subjects, and only the 7000 IU/day group (86%) achieved this a priori efficacy criterion in >80% of subjects. Change in serum 25(OH)D did not differ between HIV acquisition groups. Conclusions A 7000 IU/day D3 supplementation was safe and effective in children and young adults infected with HIV. PMID:26625449

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

    PubMed

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

    2013-07-01

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

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

    PubMed

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

    2013-07-01

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

  7. Providing vitamin D to confined sheep by oral supplementation vs ultraviolet irradiation

    SciTech Connect

    Hidiroglou, M.; Karpinski, K.

    1989-03-01

    Serial vitamin D3 (D3) and 25-hydroxyvitamin D3 (25 OH D3) concentrations of plasma were measured in confined, shorn sheep that had either been supplemented with vitamin D3 (50 micrograms/d) or exposed daily to ultraviolet irradiation (UVI). In the sheep administered D3 orally, plasma D3 increased continuously until d 35. This was followed by small fluctuations of the plasma D3 concentrations until a plateau was reached after 56 d of supplementation (.94 ng/ml plasma). Plasma 25 OH D3 concentrations increased continuously and plateaued between d 65 to 75 at about 21 ng/ml plasma. In the UVI sheep, plasma D3 and 25 OH D3 concentrations increased continuously for the first 49 d, then plateaued at 2.03 ng D3 and 29.6 ng 25 OH D3/ml. When a plateau was reached in plasma 25 OH D3 concentrations in both treatment groups, a /sup 3/H-labeled tracer dose of 25 OH D3 was given i.v., and disappearance of the /sup 3/H-labeled 25 OH D3 was followed. The UVI group had a faster decline in specific activities during the first exponential phase but a slower decline during the prolonged terminal elimination phase. These differences are reflected in the intercompartmental transfer rates. Our data indicate that UVI is as effective as oral vitamin D3 supplementation for improving vitamin D status of confined sheep.

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

    PubMed

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

    2013-10-01

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

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

    PubMed

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

    2016-01-01

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

  10. Serum 25–Hydroxyvitamin D3 and Mammography Density among Mexican Women

    PubMed Central

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

    2016-01-01

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

  11. 1α,25-Dihydroxyvitamin D3 Regulates Mitochondrial Oxygen Consumption and Dynamics in Human Skeletal Muscle Cells.

    PubMed

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

    2016-01-15

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

  12. 1α,25-Dihydroxyvitamin D3 Regulates Mitochondrial Oxygen Consumption and Dynamics in Human Skeletal Muscle Cells.

    PubMed

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

    2016-01-15

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

  13. Sunlight regulates the cutaneous production of vitamin D3 by causing its photodegradation

    SciTech Connect

    Webb, A.R.; DeCosta, B.R.; Holick, M.F.

    1989-05-01

    Exposure to sunlight initiates the formation of vitamin D3 in skin as the UV B radiation in the solar spectrum causes the photoconversion of 7-dehydrocholesterol to previtamin D3. A heat-induced isomerization then converts previtamin D3 to vitamin D3 over a period of days. A number of irradiation products of vitamin D3 are known to form upon irradiation with high intensity UV radiation, but the effect of subsequent exposures to sunlight on the vitamin D3 formed in skin is not known. To investigate this phenomenon, human skin containing vitamin D3 was exposed to sunlight in Boston. A model system of (/sup 3/H)vitamin D3 in methanol was also used to study the effects of sunlight on vitamin D3 throughout the year. Vitamin D3 proved to be exquisitely sensitive to sunlight, and once formed in the skin, exposure to sunlight resulted in its rapid photodegradation to a variety of photoproducts, including 5,6-transvitamin D3, suprasterol I, and suprasterol II.

  14. 24-Hydroxylase in Cancer: Impact on Vitamin D-based Anticancer Therapeutics

    PubMed Central

    Luo, Wei; Hershberger, Pamela A.; Trump, Donald L.; Johnson, Candace S.

    2013-01-01

    The active vitamin D hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plays a major role in regulating calcium homeostasis and bone mineralization. 1,25(OH)2D3 also modulates cellular proliferation and differentiation in a variety of cell types. 24-hydroxylase, encoded by the CYP24A1 gene, is the key enzyme which converts 1,25(OH)2D3 to less active calcitroic acid. Nearly all cell types express 24-hydroxylase, the highest activity being observed in the kidney. There is increasing evidence linking the incidence and prognosis of certain cancers to low serum 25 (OH)D3 levels and high expression of vitamin D 24-hydroxylase supporting the idea that elevated CYP24A1 expression may stimulate degradation of vitamin D metabolites including 25-(OH)D3 and 1,25(OH)2D3. The over expression of CYP24A1 in cancer cells may be a factor affecting 1,25(OH)2D3 bioavailability and anti-proliferative activity pre-clinically and clinically. The combination of 1,25(OH)2D3 with CYP24A1 inhibitors enhances 1,25(OH)2D3 mediated signaling and anti-proliferative effects and may be useful in overcoming effects of aberrant CYP24 expression. PMID:23059474

  15. Formation of fatty acid esterified vitamin D3 in rat skin by exposure to ultraviolet radiation

    SciTech Connect

    Takada, K.

    1983-04-01

    The formation of fatty acid esters of vitamin D3 was demonstrated in rat skin exposed to artificial ultraviolet rays by using multi-dimensional high-performance liquid chromatography, ultraviolet spectrophotometry, and gas-liquid chromatography-mass spectrometry. This result indicated that the fatty acid esters of 7-dehydrocholesterol in rat skin (at least 80% of 7-dehydrocholesterol in rat skin is esterified) is also isomerized into vitamin D3 ester in vivo. The initial percentage of the esterified form was 84.3% and this did not significantly change up to the time when about half of the skin total vitamin D3 disappeared (2 days). Consequently, it was speculated that the vitamin D3 ester was delivered into the blood circulation from skin without having been hydrolyzed. This was supported by the presence of vitamin D3 ester in rat plasma exposed to ultraviolet radiation. In addition, in connection with the study of the restriction of vitamin D3 synthesis, distribution of total vitamin D3 in rat skin exposed to ultraviolet irradiation in vivo was compared with that in isolated skin exposed to ultraviolet radiation. The dermal layer of the isolated skin contained about 4 times more total vitamin D3 than that of in vivo skin. This finding suggests not only that ultraviolet rays could not penetrate deeply into the in vivo skin, but that the restriction of cutaneous synthesis of vitamin D3 observed in vivo may arise from this reduced penetration of ultraviolet rays.

  16. Estimation and fortification of vitamin D3 in pasteurized process cheese.

    PubMed

    Upreti, P; Mistry, V V; Warthesen, J J

    2002-12-01

    The objective of this study was to develop methods for the estimation and fortification of vitamin D3 in pasteurized Process cheese. Vitamin D3 was estimated using alkaline saponification at 70 degrees C for 30 min, followed by extraction with petroleum ether:diethyl ether (90:10 vol/vol) and HPLC. The retention time for vitamin D3 was approximately 9 min. A standard curve with a correlation coefficient of 0.972 was prepared for quantification of vitamin D3 in unknown samples. In the second phase of the study, pasteurized Process cheeses fortified with commercial water- or fat-dispersible forms of vitamin D3 at a level of 100 IU per serving (28 g) were manufactured. There was no loss of vitamin D3 during Process cheese manufacture, and the vitamin was uniformly distributed. No losses of the vitamin occurred during storage of the fortified cheeses over a 9-mo period at 21 to 29 degrees C and 4 to 6 degrees C. There was an approximately 25 to 30% loss of the vitamin when cheeses were heated for 5 min in an oven maintained at 232 degrees C. Added vitamin D3 did not impart any off flavors to the Process cheeses as determined by sensory analysis. There were no differences between the water- and fat-dispersible forms of the vitamin in the parameters measured in fortified cheeses.

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

    NASA Astrophysics Data System (ADS)

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

    Serum 25-hydroxyvitamin D3 [25(OH)D3] is produced in the skin in response to exposure to ultraviolet radiation, and is a good indicator of vitamin D nutritional status. The aim of this study was to determine summer/winter differences in serum 25(OH)D3 and parathyroid hormone (PTH) in Japanese women and how the summer and winter values are related. The subjects were 122 healthy Japanese women aged 45-81 years (average age: 65.7 years). They were medically examined twice, in September 1997 and February 1999. Serum 25(OH)D3 and intact PTH were determined by high-performance liquid chromatography and a two-site immunoradiometric assay respectively. Lifestyle information was obtained through an interview. The seasonal differences (winter minus summer) in 25(OH)D325(OH)D3] and intact PTH concentrations were -18.8 nmol/l (SD 19.2, P<0.0001) and 0.98pmol/l (SD 1.02, P<0.0001) respectively. The correlation coefficient between summer (x) and winter (y) 25(OH)D3 levels was 0.462 (P<0.0001), with a linearly fitted line of y=0.42x+26.4. This relationship was interpreted as subjects with higher summer 25(OH)D3 values having greater reductions in winter 25(OH)D3 concentrations. There were inter-individual differences in Δ25(OH)D3, although the summer and winter 25(OH)D3 concentrations were well-correlated. Since Δ25(OH)D3 was not associated with any of the lifestyle factors, seasonal differences in the 25(OH)D3 concentrations of an individual appeared to reflect her ability to produce 25(OH)D3 photochemically in the skin. Sun bathing would be a less effective means of attaining adequate vitamin D nutritional status in a person with a small seasonal difference in 25(OH)D3, i.e., one with a low 25(OH)D3 level.

  18. SAFETY AND EFFICACY OF HIGH DOSE DAILY VITAMIN D3 SUPPLEMENTATION IN CHILDREN AND YOUNG ADULTS WITH SICKLE CELL DISEASE

    PubMed Central

    Dougherty, Kelly A.; Bertolaso, Chiara; Schall, Joan I.; Smith-Whitley, Kim; Stallings, Virginia A.

    2015-01-01

    Suboptimal vitamin D (vitD) status (<32 ng/ml) is ubiquitous among African American children with type SS sickle cell disease (SCD-SS). The vitD supplemental dose to normalize vitD status is unknown. Five to 20-year-old African-American children with (n=21) and without (n=23) SCD-SS were randomized to vitD3 supplementation (4,000 or 7,000 IU/day) and evaluated at 6- and 12-weeks for changes in vitD and SCD status. A dose was considered unsafe if serum calcium was elevated associated with elevated serum 25 hydroxyvitamin D (25(OH)D)). At baseline 95% of subjects with SCD-SS and 87% of healthy controls had suboptimal vitD status (mean ± SD, 19.2 ± 7.2 and 22.3 ± 9.3 ng/ml, respectively). After 12-weeks supplementation, both D3 doses were safe and well tolerated. Neither group achieved the a priori efficacy criterion of 25(OH)D ≥ 32 ng/ml in >80% of subjects (45% in SCD-SS and 63% in controls). However for both subjects with SCD-SS and healthy subjects by 12-weeks, deficient (< 20 ng/ml) vitD status was eliminated only in those receiving 7,000 IU/d. For subjects with SCD-SS, by 12-weeks there was a significant (all P<0.05) increase in fetal hemoglobin, decrease in HS-CRP, and reduction in the percentage of subjects with a high platelet count. PMID:25985241

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

    SciTech Connect

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

    1985-11-05

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

  20. A liposomal model that mimics the cutaneous production of vitamin D3. Studies of the mechanism of the membrane-enhanced thermal isomerization of previtamin D3 to vitamin D3

    NASA Technical Reports Server (NTRS)

    Tian, X. Q.; Holick, M. F.

    1999-01-01

    We reported previously that the rate of previtamin D3 (preD3) <==> vitamin D3 isomerization was enhanced by about 10 times in the skin compared with that in organic solvents. To elucidate the mechanism by which the rate of this reaction is enhanced in the skin, we developed a liposomal model that mimicked the enhanced isomerization of preD3 to vitamin D3 that was described in human skin. Using this model we studied the effect of changing the polarity of preD3 as well as changing the chain length and the degree of saturation of liposomal phospholipids on the kinetics of preD3 <==> vitamin D3 isomerization. We found that a decrease in the hydrophilic interaction of the preD3 with liposomal phospholipids by an esterification of the 3beta-hydroxy of preD3 (previtamin D3-3beta-acetate) reduced the rate of the isomerization by 67%. The addition of a hydroxyl on C-25 of the hydrophobic side chain (25-hydroxyprevitamin D3), which decreased the hydrophobic interaction of preD3 with the phospholipids, reduced the rate by 87%. In contrast, in an isotropic n-hexane solution, there was little difference among the rates of the conversion of preD3, its 3beta-acetate, and 25-hydroxy derivatives to their corresponding vitamin D3 compounds. We also determined rate constants (k) of preD3 <==> vitamin D3 isomerization in liposomes containing phosphatidylcholines with different carbon chain lengths. The rates of the reaction were found to be enhanced as the number of carbons (Cn) in the hydrocarbon chain of the phospholipids increased from 10 to 18. In conclusion, these results support our hypothesis that amphipathic interactions between preD3 and membrane phospholipids stabilize preD3 in its "cholesterol like" cZc-conformer, the only conformer of preD3 that can convert to vitamin D3. The stronger these interactions were, the more preD3 was likely in its cZc conformation at any moment and the faster was the rate of its conversion to vitamin D3.

  1. Comparison of analysis of vitamin D3 in foods using ultraviolet and mass spectrometric detection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A method for analysis of vitamin D3 in commonly fortified foods and in fish, which contains endogenous vitamin D3, was developed by combining the best aspects of two official methods. The ethyl ether/petroleum ether extraction procedure from AOAC 992.26 was combined with the chromatographic separat...

  2. Vitamin D3 alters microglia immune activation by an IL-10 dependent SOCS3 mechanism.

    PubMed

    Boontanrart, Mandy; Hall, Samuel D; Spanier, Justin A; Hayes, Colleen E; Olson, Julie K

    2016-03-15

    Microglia become activated immune cells during infection or disease in the central nervous system (CNS). However, the mechanisms that downregulate activated microglia to prevent immune-mediated damage are not completely understood. Vitamin D3 has been suggested to have immunomodulatory affects, and high levels of vitamin D3 have been correlated with a decreased risk for developing some neurological diseases. Recent studies have demonstrated the synthesis of active vitamin D3, 1,25-dihydroxyvitamin D3, within the CNS, but its cellular source and neuroprotective actions remain unknown. Therefore, we wanted to determine whether microglia can respond to vitamin D3 and whether vitamin D3 alters immune activation of microglia. We have previously shown that microglia become activated by IFNγ or LPS or by infection with virus to express pro-inflammatory cytokines, chemokines, and effector molecules. In this study, activated microglia increased the expression of the vitamin D receptor and Cyp27b1, which encodes the enzyme for converting vitamin D3 into its active form, thereby enhancing their responsiveness to vitamin D3. Most importantly, the activated microglia exposed to vitamin D3 had reduced expression of pro-inflammatory cytokines, IL-6, IL-12, and TNFα, and increased expression of IL-10. The reduction in pro-inflammatory cytokines was dependent on IL-10 induction of suppressor of cytokine signaling-3 (SOCS3). Therefore, vitamin D3 increases the expression of IL-10 creating a feedback loop via SOCS3 that downregulates the pro-inflammatory immune response by activated microglia which would likewise prevent immune mediated damage in the CNS. PMID:26943970

  3. Vitamin D3 alters microglia immune activation by an IL-10 dependent SOCS3 mechanism.

    PubMed

    Boontanrart, Mandy; Hall, Samuel D; Spanier, Justin A; Hayes, Colleen E; Olson, Julie K

    2016-03-15

    Microglia become activated immune cells during infection or disease in the central nervous system (CNS). However, the mechanisms that downregulate activated microglia to prevent immune-mediated damage are not completely understood. Vitamin D3 has been suggested to have immunomodulatory affects, and high levels of vitamin D3 have been correlated with a decreased risk for developing some neurological diseases. Recent studies have demonstrated the synthesis of active vitamin D3, 1,25-dihydroxyvitamin D3, within the CNS, but its cellular source and neuroprotective actions remain unknown. Therefore, we wanted to determine whether microglia can respond to vitamin D3 and whether vitamin D3 alters immune activation of microglia. We have previously shown that microglia become activated by IFNγ or LPS or by infection with virus to express pro-inflammatory cytokines, chemokines, and effector molecules. In this study, activated microglia increased the expression of the vitamin D receptor and Cyp27b1, which encodes the enzyme for converting vitamin D3 into its active form, thereby enhancing their responsiveness to vitamin D3. Most importantly, the activated microglia exposed to vitamin D3 had reduced expression of pro-inflammatory cytokines, IL-6, IL-12, and TNFα, and increased expression of IL-10. The reduction in pro-inflammatory cytokines was dependent on IL-10 induction of suppressor of cytokine signaling-3 (SOCS3). Therefore, vitamin D3 increases the expression of IL-10 creating a feedback loop via SOCS3 that downregulates the pro-inflammatory immune response by activated microglia which would likewise prevent immune mediated damage in the CNS.

  4. 1alpha,25-Dihydroxyvitamin D(3) triggered vitamin D receptor and farnesoid X receptor-like effects in rat intestine and liver in vivo.

    PubMed

    Chow, Edwin C Y; Maeng, Han-Joo; Liu, Shanjun; Khan, Ansar A; Groothuis, Geny M M; Pang, K Sandy

    2009-11-01

    1alpha,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), a natural ligand of the vitamin D receptor (VDR), was found to increase the rat ileal Asbt and bile acid absorption. The effects of VDR, whose expression is low in liver, on hepatic transporters and enzymes are unknown. Protein and mRNA levels of target genes in the small intestine, colon and liver after intraperitoneal dosing of 1,25(OH)(2)D(3) (0-2.56 nmol/kg/day for 4 days) to the rat were determined by Western blotting and qPCR, respectively. The 1,25(OH)(2)D(3) treatment increased total Cyp3a protein and Cyp3a1 mRNA expressions in the proximal small intestine, and the short heterodimer partner (SHP), the fibroblast growth factor 15 (FGF15), organic solute transporter (Ostalpha and Ostbeta) mRNA and Asbt protein expressions in the ileum. About 50% higher portal bile acid concentration (65.1+/-14.9 vs 41.9+/-7.8 microm, p<0.05) and elevated expressions of the hepatic farnesoid X receptor (FXR) and SHP mRNA resulted with 1,25(OH)(2)D(3) treatment. Increased Bsep and Ostalpha mRNA expressions in liver and a>50% reduction in the Cyp7a1 protein level (p<0.05) and cholesterol metabolism in rat liver microsomes (p=0.002), likely consequences of the bile acid-FXR-SHP cascade and activation of the signaling pathway for Cyp7a1 inhibition by FGF15, were found. Increased hepatic multidrug resistance-associated protein (Mrp3) and multidrug resistance protein 1a (Mdr1a) mRNA and P-gp protein were also observed. It was concluded that the changes in hepatic transporters and enzymes in the rat were indirect, secondary effects of the liver FXR-SHP cascade due to increased intestinal absorption of bile acids and elevated levels of FGF15, events that led to the activation of FXR.

  5. A Randomized Controlled Trial on the Effect of Vitamin D3 on Inflammation and Cathelicidin Gene Expression in Ulcerative Colitis Patients

    PubMed Central

    Sharifi, Amrollah; Hosseinzadeh-Attar, Mohammad Javad; Vahedi, Homayoon; Nedjat, Saharnaz

    2016-01-01

    Background: Inflammatory bowel disease (IBD) is an intestinal chronic inflammatory condition and includes Crohn's disease (CD) and ulcerative colitis (UC). It has been proposed that Vitamin D supplementation may have a beneficial role in IBD. Aim: To characterize the effects of Vitamin D on cathelicidin (hCAP/LL37) gene expression, ESR, and serum hs-CRP levels. Materials and Methods: Ninety UC patients on remission were randomized to receive 300,000 IU intramuscular Vitamin D or 1 mL normal saline as placebo, respectively. Before and 90 days after intervention, serum levels of 25 (OH)-Vitamin D3, PTH, Calcium, ESR, and hs-CRP were measured. Cathelicidin gene expression was also quantified using qRT-PCR. Results: Baseline serum 25-OH-Vitamin D3 levels were not different between the two groups and after intervention, increased only in Vitamin D group (P < 0.001). Hs-CRP levels were lower in Vitamin D group after intervention (Before: 3.43 ± 3.47 vs 3.86 ± 3.55 mg/L, P = 0.56; after: 2.31 ± 2.25 vs 3.90 ± 3.97 mg/L, P = 0.023). ESR decreased significantly in Vitamin D group (Before: 12.4 ± 6.1 vs 12.1 ± 5.3 mm/h, P = 0.77; after: 6.7 ± 4.5 vs 11.4 ± 5.5 mm/h, P < 0.001). The mean fold change in hCAP18 gene expression in Vitamin D group was significantly higher than placebo group. (Mean ± SD: 3.13 ± 2.56 vs 1.09 ± 0.56; median ± interquartile range: 2.17 ± 3.81 vs 0.87 ± 0.53, P < 0.001). Conclusion: Decreases in ESR and hs-CRP levels and increase in LL37 gene expression support the hypothesis that Vitamin D supplementation may have a beneficial role in UC patients. PMID:27488327

  6. Characterization of the translocation process of vitamin D3 from the skin into the circulation.

    PubMed

    Tian, X Q; Chen, T C; Lu, Z; Shao, Q; Holick, M F

    1994-08-01

    The cutaneous synthesis of vitamin D3 and the subsequent translocation of vitamin D3 into the circulation are two key steps in the vitamin D endocrine system. To study the kinetic aspects of cutaneous synthesis and translocation of vitamin D3, both in vitro and in vivo chicken models have been developed. To assess the capacity of chicken skin to generate vitamin D3, the concentrations of 7-dehydrocholesterol (7-DHC) in different skin areas were determined. It was found that the highest concentration of 7-DHC was in the leg skin (3524 +/- 937 ng cm-2), which was about 30 times greater than that in the back (120 +/- 62 ng cm-2). Whole body exposure of chickens to UV-B radiation (0.5 J cm-2) resulted in the production of previtamin D3 (preD3) in the skin of the legs and feet (43 +/- 7 and 54 +/- 17 ng cm-2, respectively), whereas no preD3 was detected in the back skin. In vitro, at 40 C, the forward (k1) and reverse (k2) rate constants of the preD3<-->vitamin D3 reaction in the leg skin were greatly increased compared to those in n-hexane (k1, 0.367 vs. 0.0369 h-1; k2, 0.042 vs. 0.0059 h-1). In vivo, the determined rate constants k1, k2, and k3 for the consecutive reactions preD3<-->vitamin D3-->vitamin D3 were 0.257, 0.034, and 0.114 h-1, respectively. To evaluate the circulating concentration of vitamin D3 in response to UV-B radiation, chicken legs were irradiated. The time course revealed a 4-fold increase in the circulating concentration of vitamin D3, with a peak about 30 h postradiation. No appreciable amount of preD3 could be detected in the circulation in the early hours after UV-B radiation, suggesting the existence of a process responsible for the specific translocation of vitamin D3 from the skin into the circulation. PMID:8033813

  7. Vitamin D Promotes Odontogenic Differentiation of Human Dental Pulp Cells via ERK Activation

    PubMed Central

    Woo, Su-Mi; Lim, Hae-Soon; Jeong, Kyung-Yi; Kim, Seon-Mi; Kim, Won-Jae; Jung, Ji-Yeon

    2015-01-01

    The active metabolite of vitamin D such as 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) is a well-known key regulatory factor in bone metabolism. However, little is known about the potential of vitamin D as an odontogenic inducer in human dental pulp cells (HDPCs) in vitro. The purpose of this study was to evaluate the effect of vitamin D3 metabolite, 1α,25(OH)2D3, on odontoblastic differentiation in HDPCs. HDPCs extracted from maxillary supernumerary incisors and third molars were directly cultured with 1α,25(OH)2D3 in the absence of differentiation-inducing factors. Treatment of HDPCs with 1α,25(OH)2D3 at a concentration of 10 nM or 100 nM significantly upregulated the expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein1 (DMP1), the odontogenesis-related genes. Also, 1α,25(OH)2D3 enhanced the alkaline phosphatase (ALP) activity and mineralization in HDPCs. In addition, 1α,25(OH)2D3 induced activation of extracellular signal-regulated kinases (ERKs), whereas the ERK inhibitor U0126 ameliorated the upregulation of DSPP and DMP1 and reduced the mineralization enhanced by 1α,25(OH)2D3. These results demonstrated that 1α,25(OH)2D3 promoted odontoblastic differentiation of HDPCs via modulating ERK activation. PMID:26062551

  8. Noncalcemic actions of 1,25-dihydroxyvitamin D3 and clinical applications.

    PubMed

    Holick, M F

    1995-08-01

    Vitamin D is absolutely essential for the maintenance of a healthy skeleton. Without vitamin D, children develop rickets and adults exacerbate their osteoporosis and develop osteomalacia. Casual exposure to sunlight is the major source of vitamin D for most people. During exposure to sunlight, ultraviolet B photons photolyze cutaneous stores of 7-dehydrocholesterol to previtamin D3. Previtamin D3 undergoes a thermal isomerization to form vitamin D3. Increased skin pigmentation, changes in latitude, time of day, sunscreen use, and aging can have a marked influence on the cutaneous production of vitamin D3. Once vitamin D3 is formed in the skin or ingested in the diet, it must be hydroxylated in the liver and kidney to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. It is now recognized that a wide variety of tissues and cells, both related to calcium metabolism and unrelated to calcium metabolism, are target sites for 1,25(OH)2D3. 1,25(OH)2D3 stimulates intestinal calcium absorption and mobilizes stem cells to mobilize calcium stores from bone. Noncalcemic tissues that possess receptors for 1,25(OH)2D3 respond to the hormone in a variety of ways. Of great interest is that 1,25(OH)2D3 is a potent antiproliferative and prodifferentiation mediator. As a result, 1,25(OH)2D3 and its analogs have wide clinical application in such diverse clinical disorders as rheumatoid and psoriatic arthritis; diabetes mellitus type I; hypertension; cardiac arrhythmias; seizure disorders; cancers of the breast, prostate, and colon; some leukemias and myeloproliferative disorders; chemotherapy-induced hair loss; and skin rejuvenation as well as skin diseases like psoriasis and ichthyosis.

  9. Noncalcemic actions of 1,25-dihydroxyvitamin D3 and clinical applications.

    PubMed

    Holick, M F

    1995-08-01

    Vitamin D is absolutely essential for the maintenance of a healthy skeleton. Without vitamin D, children develop rickets and adults exacerbate their osteoporosis and develop osteomalacia. Casual exposure to sunlight is the major source of vitamin D for most people. During exposure to sunlight, ultraviolet B photons photolyze cutaneous stores of 7-dehydrocholesterol to previtamin D3. Previtamin D3 undergoes a thermal isomerization to form vitamin D3. Increased skin pigmentation, changes in latitude, time of day, sunscreen use, and aging can have a marked influence on the cutaneous production of vitamin D3. Once vitamin D3 is formed in the skin or ingested in the diet, it must be hydroxylated in the liver and kidney to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. It is now recognized that a wide variety of tissues and cells, both related to calcium metabolism and unrelated to calcium metabolism, are target sites for 1,25(OH)2D3. 1,25(OH)2D3 stimulates intestinal calcium absorption and mobilizes stem cells to mobilize calcium stores from bone. Noncalcemic tissues that possess receptors for 1,25(OH)2D3 respond to the hormone in a variety of ways. Of great interest is that 1,25(OH)2D3 is a potent antiproliferative and prodifferentiation mediator. As a result, 1,25(OH)2D3 and its analogs have wide clinical application in such diverse clinical disorders as rheumatoid and psoriatic arthritis; diabetes mellitus type I; hypertension; cardiac arrhythmias; seizure disorders; cancers of the breast, prostate, and colon; some leukemias and myeloproliferative disorders; chemotherapy-induced hair loss; and skin rejuvenation as well as skin diseases like psoriasis and ichthyosis. PMID:8579891

  10. Vitamin D and inflammation

    PubMed Central

    Cannell, John J; Grant, William B; Holick, Michael F

    2014-01-01

    Several studies found an inverse relationship between 25-hydroxyvitamin D [25(OH)D] and markers of inflammation. A controversy exists as to whether vitamin D lowers inflammation or whether inflammation lowers 25(OH)D concentrations. Certainly 25(OH)D concentrations fall after major surgery. However, is this due to inflammation lowering 25(OH)D or is 25(OH)D being metabolically cleared by the body to quell inflammation. We searched the literature and found 39 randomized controlled trials (RCT) of vitamin D and markers of inflammation. Seventeen found significantly reduced inflammatory markers, 19 did not, one was mixed and one showed adverse results. With few exceptions, studies in normal subjects, obesity, type 2 diabetics, and stable cardiovascular disease did not find significant beneficial effects. However, we found that 6 out of 7 RCTS of vitamin D3 in highly inflammatory conditions (acute infantile congestive heart failure, multiple sclerosis, inflammatory bowel disease, cystic fibrosis, SLE, active TB and evolving myocardial infarction) found significant reductions. We found baseline and final 25(OH)D predicted RCTs with significant reduction in inflammatory markers. Vitamin D tends to modestly lower markers of inflammation in highly inflammatory conditions, when baseline 25(OH)D levels were low and when achieved 25(OH)D levels were higher. Future inquiries should: recruit subjects with low baseline 25(OH)D levels, subjects with elevated markers of inflammation, subjects with inflammatory conditions, achieve adequate final 25(OH)D levels, and use physiological doses of vitamin D. We attempted to identify all extant randomized controlled trials (RCTs) of vitamin D that used inflammatory markers as primary or secondary endpoints. PMID:26413186

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

    PubMed Central

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

    2008-01-01

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

  12. 1,25-(OH){sub 2}-vitamin D{sub 3} prevents activation of hepatic stellate cells in vitro and ameliorates inflammatory liver damage but not fibrosis in the Abcb4{sup −/−} model

    SciTech Connect

    Reiter, Florian P.; Hohenester, Simon; Nagel, Jutta M.; Wimmer, Ralf; Artmann, Renate; Wottke, Lena; Makeschin, Marie-Christine; Mayr, Doris; Rust, Christian; Trauner, Michael; Denk, Gerald U.

    2015-04-03

    Background/Purpose of the study: Vitamin D{sub 3}-deficiency is common in patients with chronic liver-disease and may promote disease progression. Vitamin D{sub 3}-administration has thus been proposed as a therapeutic approach. Vitamin D{sub 3} has immunomodulatory effects and may modulate autoimmune liver-disease such as primary sclerosing cholangitis. Although various mechanisms of action have been proposed, experimental evidence is limited. Here we test the hypothesis that active 1,25-(OH){sub 2}-vitamin D{sub 3} inhibits activation of hepatic stellate cells (HSC) in vitro and modulates liver-injury in vivo. Methods: Proliferation and activation of primary murine HSC were assessed by BrdU- and PicoGreen{sup ®}-assays, immunoblotting, immunofluorescence-microscopy, quantitative-PCR, and zymography following calcitriol-treatment. Wild-type and ATP-binding cassette transporter b4{sup −/−} (Abcb4{sup −/−})-mice received calcitriol for 4 weeks. Liver-damage, inflammation, and fibrosis were assessed by serum liver-tests, Sirius-red staining, quantitative-PCR, immunoblotting, immunohistochemistry and hydroxyproline quantification. Results: In vitro, calcitriol inhibited activation and proliferation of murine HSC as shown by reduced α-smooth muscle actin and platelet-derived growth factor-receptor-β-protein-levels, BrdU and PicoGreen®-assays. Furthermore, mRNA-levels and activity of matrix metalloproteinase 13 were profoundly increased. In vivo, calcitriol ameliorated inflammatory liver-injury reflected by reduced levels of alanine aminotransferase in Abcb4{sup −/−}-mice. In accordance, their livers had lower mRNA-levels of F4/80, tumor necrosis factor-receptor 1 and a lower count of portal CD11b positive cells. In contrast, no effect on overall fibrosis was observed. Conclusion: Calcitriol inhibits activation and proliferation of HSCs in vitro. In Abcb4{sup −/−}-mice, administration of calcitriol ameliorates inflammatory liver-damage but has

  13. Systemic treatments with the low-calcemic 1,25(OH)(2)D(3) analogs JKF or QW increase both the morphological and biochemical responses to estradiol-17beta in rat tibiae.

    PubMed

    Somjen, D; Katzburg, S; Posner, G H; Livne, E; Kaye, A M

    2007-04-15

    We demonstrated previously that daily injection for 3 days of the less calcemic vitamin D analogs: JK 1624 F(2)-2 (JKF) and QW 1624F(2)-2 (QW) followed by estradiol-17beta (E(2)) in female rats upregulated creatine kinase-specific activity (CK) in skeletal tissues. In this study, we evaluated both histomorphological and biochemical changes due to a regime of 4 days treatment with JKF or QW, followed by injection of E(2) on day 5, repeated for 2.5 months. Ovariectomized female rats (Ovx) were injected 2 weeks after surgery, with JKF or QW at 0.2 ng/g BW followed by injections of E(2) (1 microg/rat) on day 5 of each week for 2.5 months. Rats were sacrificed 24 h after the last injection and bones were analyzed. JKF alone decreased growth plate width, increased % total bone volume (%TBV), with no change in cortical thickness. In contrast, QW restored growth plate width and %TBV with no change in cortical thickness. Combined with E(2), JKF restored %TBV and growth plate width but with no change in cortical thickness, while QW restored significantly all parameters including cortical thickness. Moreover, there was also an increase in the responsiveness of CK to E(2) in epiphyseal cartilage and diaphyseal bone but not in uterus. Thus, vitamin D less calcemic analogs increased responsiveness to E(2) morphologically as well as biochemically. We, therefore, conclude that combined treatment of less calcemic analogs vitamin D and E(2) might be superior for treatment of bone damage caused by ovariectomy in female rats and might be applied for post-menopausal osteoporosis.

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

    PubMed

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

    2008-06-01

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

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

    PubMed Central

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

    2016-01-01

    Background: 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. Materials and Methods: 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. Results: 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. Conclusion: 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. PMID:27110549

  16. 25-Hydroxyvitamin D Can Interfere With a Common Assay for 1,25-Dihydroxyvitamin D in Vitamin D Intoxication

    PubMed Central

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

    2015-01-01

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

  17. Investigating causality in the association between 25(OH)D and schizophrenia

    PubMed Central

    Taylor, Amy E.; Burgess, Stephen; Ware, Jennifer J.; Gage, Suzanne H.; Richards, J. Brent; Davey Smith, George; Munafò, Marcus R.

    2016-01-01

    Vitamin D deficiency is associated with increased risk of schizophrenia. However, it is not known whether this association is causal or what the direction of causality is. We performed two sample bidirectional Mendelian randomization analysis using single nucleotide polymorphisms (SNPs) robustly associated with serum 25(OH)D to investigate the causal effect of 25(OH)D on risk of schizophrenia, and SNPs robustly associated with schizophrenia to investigate the causal effect of schizophrenia on 25(OH)D. We used summary data from genome-wide association studies and meta-analyses of schizophrenia and 25(OH)D to obtain betas and standard errors for the SNP-exposure and SNP-outcome associations. These were combined using inverse variance weighted fixed effects meta-analyses. In 34,241 schizophrenia cases and 45,604 controls, there was no clear evidence for a causal effect of 25(OH)D on schizophrenia risk. The odds ratio for schizophrenia per 10% increase in 25(OH)D conferred by the four 25(OH)D increasing SNPs was 0.992 (95% CI: 0.969 to 1.015). In up to 16,125 individuals with measured serum 25(OH)D, there was no clear evidence that genetic risk for schizophrenia causally lowers serum 25(OH)D. These findings suggest that associations between schizophrenia and serum 25(OH)D may not be causal. Therefore, vitamin D supplementation may not prevent schizophrenia. PMID:27215954

  18. The Effects of Fat-soluble Vitamin Administration on Plasma Vitamin Status of Nursing Pigs Differ When Provided by Oral Administration or Injection

    PubMed Central

    Jang, Y. D.; Lindemann, M. D.; Monegue, H. J.; Stuart, R. L.

    2014-01-01

    Four experiments were conducted to investigate the effect of fat-soluble vitamin administration to sows or newborn pigs on plasma vitamin status. In Exp. 1 and 2, a total of 24 and 43 newborn pigs were allotted to control and vitamin treatments (vitamin D3 with variable addition of vitamins A and E) orally or by i.m. injection. In Exp. 3, pigs from Exp. 2 were allotted to 2 treatments (±vitamins D3 and E in drinking water) for 14 d postweaning. In Exp. 4, twenty-four gestating sows were used for 2 treatments (±injection of a vitamin D3/A/E product 2 wk prepartum). In Exp. 1 and 2, when vitamin D3 was administrated orally or by i.m. injection on d 1 of age, pigs had increased plasma 25-hydroxycholecalciferol (25-OH D3) concentration 10 d after administration compared with control pigs (p<0.05). The injectable administration with vitamin D3 and E was able to achieve higher plasma 25-OH D3 (p<0.05) and α-tocopherol (p<0.05) concentrations than oral administration. At weaning, the pigs in the injection group had higher plasma 25-OH D3 concentration than those in the other groups in both studies (p<0.05). In Exp. 3, water supplementation of vitamin D3 and E postweaning increased plasma 25-OH D3 and α-tocopherol concentrations at d 14 postweaning (p<0.01). In Exp. 4, when sows were injected with the vitamin D3 product prepartum, serum 25-OH D3 concentrations of sows at farrowing (p<0.01), and in their progeny at birth (p<0.01) and weaning (p<0.05) were increased. These results demonstrated that fat-soluble vitamin administration to newborn pigs increased plasma 25-OH D3 concentration regardless of administration routes and α-tocopherol concentration by the injectable route, and that water supplementation of vitamin D3 and E to nursery pigs increased plasma 25-OH D3 and α-tocopherol concentrations. Additionally, injecting sows with vitamin D3 prepartum increased 25-OH D3 in sows and their offspring. If continued research demonstrates that the serum levels of 25-OH D

  19. Effects of pharmacological doses of Vitamin D3 on mineral balance and profiles of plasma Vitamin D3 metabolites in horses.

    PubMed

    Harmeyer, Johein; Schlumbohm, Christina

    2004-05-01

    Metabolism and functions of Vitamin D in horses differ from those in humans, pigs and rats. In horses, calcidiol and calcitriol concentrations in blood plasma are remarkably low (<10 nmol L(-1); 20-40 pmol L(-1), respectively). When a toxic amount of Vitamin D(3) is administered, the responsiveness of calcium and calcitriol concentrations in blood plasma is much reduced compared to the other domestic animal species but inorganic phosphate (Pi) response is much more marked, leading to an increase of the Ca x Pi product. Also, soft tissue calcifications have been observed to develop in horses during Vitamin D(3) intoxication. It was suggested that the elevation of the Ca x Pi product may play a causative role in this calcification process. To test this assumption, two horses were treated with 40,000 IU kg(-1) of Vitamin D(3) whilst dietary uptake of Ca and Pi was restricted to prevent or to diminish the increase of the Ca x Pi product. Distribution, number and severity of calcification centres were considerably less in these horses than in the control animals of a previous experiment which had received the same amount of Vitamin D(3) but where Ca and Pi intake was not restricted. It appears from these findings that in horses, the increase of the Ca x Pi product in blood plasma during a Vitamin D intoxication contributes to the soft tissue calcifications. It is further concluded that in the event of a Vitamin D intoxication, it is recommended to restrict the Ca and Pi uptake immediately. The authors believe that this may help to prevent or at least diminish soft tissue calcifications which are often fatal to the horse due to nephrocalcinosis.

  20. The Synthesis of Active Metabolites and Analogues of Vitamin D3

    NASA Astrophysics Data System (ADS)

    Yakhimovich, R. I.

    1980-04-01

    The literature date on the synthesis of the active metabolites and analogues of vitamin D3 (cholecalciferol), which play an important role in regulating the homeostatis of calcium in the organism, are reviewed. The bibliography includes 150 references.

  1. Primary vitamin D target genes allow a categorization of possible benefits of vitamin D₃ supplementation.

    PubMed

    Carlberg, Carsten; Seuter, Sabine; de Mello, Vanessa D F; Schwab, Ursula; Voutilainen, Sari; Pulkki, Kari; Nurmi, Tarja; Virtanen, Jyrki; Tuomainen, Tomi-Pekka; Uusitupa, Matti

    2013-01-01

    Vitamin D deficiency has been associated with an increased risk of developing a number of diseases. Here we investigated samples from 71 pre-diabetic individuals of the VitDmet study, a 5-month high dose vitamin D3 intervention trial during Finnish winter, for their changes in serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations and the expression of primary vitamin D target genes in peripheral blood mononuclear cells and adipose tissue. A negative correlation between serum concentrations of parathyroid hormone and 25(OH)D3 suggested an overall normal physiological vitamin D response among the participants. The genes CD14 and thrombomodulin (THBD) are up-regulated primary vitamin D targets and showed to be suitable gene expression markers for vitamin D signaling in both primary tissues. However, in a ranking of the samples concerning their expected response to vitamin D only the top half showed a positive correlation between the changes of CD14 or THBD mRNA and serum 25(OH)D3 concentrations. Interestingly, this categorization allows unmasking a negative correlation between changes in serum concentrations of 25(OH)D3 and the inflammation marker interleukin 6. We propose the genes CD14 and THBD as transcriptomic biomarkers, from which the effects of a vitamin D3 supplementation can be evaluated. These biomarkers allow the classification of subjects into those, who might benefit from a vitamin D3 supplementation, and others who do not.

  2. 1,25 Dihydroxyvitamin D3 Inhibits TGFβ1-Mediated Primary Human Cardiac Myofibroblast Activation

    PubMed Central

    Meredith, Anna; Boroomand, Seti; Carthy, Jon; Luo, Zongshu; McManus, Bruce

    2015-01-01

    Aims Epidemiological and interventional studies have suggested a protective role for vitamin D in cardiovascular disease, and basic research has implicated vitamin D as a potential inhibitor of fibrosis in a number of organ systems; yet little is known regarding direct effects of vitamin D on human cardiac cells. Given the critical role of fibrotic responses in end stage cardiac disease, we examined the effect of active vitamin D treatment on fibrotic responses in primary human adult ventricular cardiac fibroblasts (HCF-av), and investigated the relationship between circulating vitamin D (25(OH)D3) and cardiac fibrosis in human myocardial samples. Methods and Results Interstitial cardiac fibrosis in end stage HF was evaluated by image analysis of picrosirius red stained myocardial sections. Serum 25(OH)D3 levels were assayed using mass spectrometry. Commercially available HCF-av were treated with transforming growth factor (TGF)β1 to induce activation, in the presence or absence of active vitamin D (1,25(OH)2D3). Functional responses of fibroblasts were analyzed by in vitro collagen gel contraction assay. 1,25(OH)2D3 treatment significantly inhibited TGFβ1-mediated cell contraction, and confocal imaging demonstrated reduced stress fiber formation in the presence of 1,25(OH)2D3. Treatment with 1,25(OH)2D3 reduced alpha-smooth muscle actin expression to control levels and inhibited SMAD2 phosphorylation. Conclusions Our results demonstrate that active vitamin D can prevent TGFβ1-mediated biochemical and functional pro-fibrotic changes in human primary cardiac fibroblasts. An inverse relationship between vitamin D status and cardiac fibrosis in end stage heart failure was observed. Collectively, our data support an inhibitory role for vitamin D in cardiac fibrosis. PMID:26061181

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

    PubMed

    Konishi, Yoko; Yamanaka, Keiichi; Mizutani, Hitoshi

    2012-01-01

    We report 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.

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

    SciTech Connect

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

    1985-06-01

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

  5. Vitamin D, steroid hormones, and autoimmunity.

    PubMed

    Cutolo, Maurizio; Paolino, Sabrina; Sulli, Alberto; Smith, Vanessa; Pizzorni, Carmen; Seriolo, Bruno

    2014-05-01

    The endogenous serum metabolite of vitamin D (calcitriol, 1,25(OH)2 D3 ) is considered a true steroid hormone (D hormone), and like glucocorticoids (GCs) and gonadal hormones, may exert several immunomodulatory activities. Serum vitamin D deficiency (25(OH) D), and therefore reduced 1,25(OH)2 D3 availability, is considered a risk factor for several chronic/inflammatory or autoimmune conditions, including infectious diseases, type 1 diabetes, multiple sclerosis, and especially autoimmune rheumatic diseases (ARD). In ARD in particular, 1,25(OH)2 D3 regulates both innate and adaptive immunity, potentiating the innate response (antimicrobial activity) but reducing adaptive immunity (antigen presentation, T and B cell activities). Regarding a possible synergism between vitamin D and GCs, several studies show that 1,25(OH)2 D3 has significant additive effects on dexamethasone-mediated inhibition of human lymphocyte and monocyte proliferation. Conversely, vitamin D deficiency seems to play a role in increasing autoantibody production by B cells, and seasonal vitamin D declines may trigger flares in ARD, as recently shown. Finally, 1,25(OH)2 D3 seems to reduce aromatase activity and limit the negative effects related to increased peripheral estrogen metabolism (cell proliferation, B cell overactivity).

  6. What Is Vitamin D3 and Its Potential Use in Dermatology?

    PubMed

    Sánchez-Armendáriz, Karen; García-Gil, Ana; Domínguez-Cherit, Judith

    2016-01-01

    There are many clinical studies that show the importance of vitamin D in multiple skin disorders. Understanding the molecular elements of cathelicidin expression might lead to new treatments and help explain mechanisms of current therapies. Overall, current data are generating many questions and expectations and require larger trials to confirm the therapeutic use of vitamin D3 supplementation. Vitamin D now represents a vast and promising field of research to dermatologists. PMID:27502255

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

    PubMed

    Connelly, Sandra J; Walling, Kelly; Wilbert, Steven A; Catlin, Diane M; Monaghan, Cailin E; Hlynchuk, Sofiya; Meehl, Pamela G; Resch, Lauren N; Carrera, J Valerie; Bowles, Stephanie M; Clark, Michael D; Tan, Loraine T; Cody, Jeremy A

    2015-01-01

    Ultraviolet radiation is known to be highly variable in aquatic ecosystems. It has been suggested that UV-exposed organisms may demonstrate enough phenotypic plasticity to maintain the relative fitness of natural populations. Our long-term objective is to determine the potential photoprotective effect of vitamin D3 on Daphnia pulex exposed to acute or chronic UV radiation. Herein we report our initial findings in this endeavor. D. pulex survival and reproduction (fitness) was monitored for 5 d as a proof of concept study. Significantly higher fitness was observed in the D. pulex with D3 than those without (most extreme effects observed were 0% survival in the absence of D3 and 100% with 10 ppm D3). Vitamin D3 was isolated from the culture media, the algal food (Pseudokirchneriella), and the D. pulex and quantified using high performance liquid chromatography (HPLC). Vitamin D3 was fluorescently labeled using a phenothiazinium dye and added to cultures of D. pulex. Images demonstrating the uptake of D3 into the tissues and carapace of the D. pulex were acquired. Our initial findings suggest a positive role for D3 in ecosystems as both UV-stressed algae and Daphnia sequester D3, and D. pulex demonstrate increased fitness in the presence of D3.

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

    PubMed Central

    Walling, Kelly; Wilbert, Steven A.; Catlin, Diane M.; Monaghan, Cailin E.; Hlynchuk, Sofiya; Meehl, Pamela G.; Resch, Lauren N.; Carrera, J. Valerie; Bowles, Stephanie M.; Clark, Michael D.

    2015-01-01

    Ultraviolet radiation is known to be highly variable in aquatic ecosystems. It has been suggested that UV-exposed organisms may demonstrate enough phenotypic plasticity to maintain the relative fitness of natural populations. Our long-term objective is to determine the potential photoprotective effect of vitamin D3 on Daphnia pulex exposed to acute or chronic UV radiation. Herein we report our initial findings in this endeavor. D. pulex survival and reproduction (fitness) was monitored for 5 d as a proof of concept study. Significantly higher fitness was observed in the D. pulex with D3 than those without (most extreme effects observed were 0% survival in the absence of D3 and 100% with 10 ppm D3). Vitamin D3 was isolated from the culture media, the algal food (Pseudokirchneriella), and the D. pulex and quantified using high performance liquid chromatography (HPLC). Vitamin D3 was fluorescently labeled using a phenothiazinium dye and added to cultures of D. pulex. Images demonstrating the uptake of D3 into the tissues and carapace of the D. pulex were acquired. Our initial findings suggest a positive role for D3 in ecosystems as both UV-stressed algae and Daphnia sequester D3, and D. pulex demonstrate increased fitness in the presence of D3. PMID:26147286

  9. A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1).

    PubMed

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

    2003-12-01

    Metabolites of vitamin D3 (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. The metabolism of D3 has been extensively studied, and a role for three different mitochondrial cytochrome P450s (CYP24A, CYP27A, and CYP27B1) has been described that catalyze the formation of the 24(OH), 25(OH), and 1(OH) metabolites of D3, respectively. The hormone 1,25-dihydroxyvitamin D3 has been most extensively studied and is widely recognized as a regulator of calcium and phosphorous metabolism. Hydroxylated metabolites of D3 interact with the nuclear receptor and thereby influence growth, cellular differentiation, and proliferation. In this article, we describe in vitro experiments using purified mitochondrial cytochrome P450scc (CYP11A1) reconstituted with the iron-sulfer protein, adrenodoxin, and the flavoprotein, adrenodoxin reductase, and show the NADPH and time-dependent formation of two major metabolites of D3 (i.e., 20-hydroxyvitamin D3 and 20,22-dihydroxyvitamin D3) plus two unknown minor metabolites. In addition, we describe the metabolism of 7-dehydrocholesterol by CYP11A1 to a single product identified as 7-dehydropregnenolone. Although the physiological importance of these hydroxylated metabolites of D3 and their in vivo formation and mode of action remain to be determined, the rate with which they are formed by CYP11A1 in vitro suggests an important role.

  10. Metabolism of 20-hydroxyvitamin D3 by mouse liver microsomes.

    PubMed

    Cheng, Chloe Y S; Slominski, Andrzej T; Tuckey, Robert C

    2014-10-01

    20-Hydroxyvitamin D3 [20(OH)D3], the major product of CYP11A1 action on vitamin D3, is biologically active and like 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can inhibit proliferation and promote differentiation of a range of cells, and has anti-inflammatory properties. However, unlike 1,25(OH)2D3, it does not cause toxic hypercalcemia at high doses and is therefore a good candidate for therapeutic use to treat hyperproliferative and autoimmune disorders. In this study we analyzed the ability of mouse liver microsomes to metabolize 20(OH)D3. The two major products were identified from authentic standards as 20,24-dihydroxyvitamin D3 [20,24(OH)2D3] and 20,25-dihydroxyvitamin D3 [20,25(OH)2D3]. The reactions for synthesis of these two products from 20(OH)D3 displayed similar Km values suggesting that they were catalyzed by the same cytochrome P450. Some minor metabolites were produced by reactions with higher Km values for 20(OH)D3. Some metabolites gave mass spectra suggesting that they were the result of hydroxylation followed by dehydrogenation. One product had an increase in the wavelength for maximum absorbance from 263nm seen for 20(OH)D3, to 290nm, suggesting a new double bond was interacting with the vitamin D-triene chromophore. The two major products, 20,24(OH)2D3 and 20,25(OH)2D3 have both previously been shown to have higher potency for inhibition of colony formation by melanoma cells than 20(OH)D3, thus it appears that metabolism of 20(OH)D3 by mouse liver microsomes can generate products with enhanced activity. PMID:25138634

  11. Metabolism of 20-hydroxyvitamin D3 by mouse liver microsomes

    PubMed Central

    Cheng, Chloe Y.S.; Slominski, Andrzej T.; Tuckey, Robert C.

    2014-01-01

    20-Hydroxyvitamin D3 [20(OH)D3], the major product of CYP11A1 action on vitamin D3, is biologically active and like 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can inhibit proliferation and promote differentiation of a range of cells, and has anti-inflammatory properties. However, unlike 1,25(OH)2D3, it does not cause toxic hypercalcemia at high doses and is therefore a good candidate for therapeutic use to treat hyperproliferative and autoimmune disorders. In this study we analyzed the ability of mouse liver microsomes to metabolize 20(OH)D3. The two major products were identified from authentic standards as 20,24-dihydroxyvitamin D3 [20,24(OH)2D3] and 20,25-dihydroxyvitamin D3 [20,25(OH)2D3]. The reactions for synthesis of these two products from 20(OH)D3 displayed similar Km values suggesting that they were catalyzed by the same cytochrome P450. Some minor metabolites were produced by reactions with higher Km values for 20(OH)D3. Some metabolites gave mass spectra suggesting that they were the result of hydroxylation followed by dehydrogenation. One product had an increase in the wavelength for maximum absorbance from 263 nm seen for 20(OH)D3, to 290 nm, suggesting a new double bond was interacting with the vitamin D-triene chromophore. The two major products, 20,24(OH)2D3 and 20,25(OH)2D3 have both previously been shown to have higher potency for inhibition of colony formation by melanoma cells than 20(OH)D3, thus it appears that metabolism of 20(OH)D3 by mouse liver microsomes can generate products with enhanced activity. PMID:25138634

  12. Single high-dose vitamin D at birth corrects vitamin D deficiency in infants in Mexico.

    PubMed

    Moodley, Amaran; Spector, Stephen A

    2015-05-01

    This study examined the prevalence of vitamin D deficiency in mothers and infants in Tijuana, Mexico and determined the effect of a single oral dose of 50,000 IU vitamin D3 at birth on 25-hydroxyvitamin D (25[OH]D) levels during infancy. Healthy infants were randomized to receive vitamin D3 or placebo at birth. At birth 23% of infants were vitamin D deficient and 77% had vitamin D insufficiency (mean 25[OH]D level 18.9 ng/ml); 10% of mothers were vitamin D deficient and 61% were insufficient. Infants receiving vitamin D3 had higher 25(OH)D levels at two months (N = 29; 33.9 versus 24.2 ng/ml) and six months (N = 21; 36.5 versus 27.4 ng/ml). Exclusively breastfed infants had lower 25(OH)D levels at two months (14.9 versus 33.4 ng/ml). Vitamin D deficiency is common in infants and mothers in Tijuana, Mexico. A single dose of vitamin D3 at birth was safe and significantly increased 25(OH)D levels during infancy.

  13. A role for interleukin-1 alpha in the 1,25 dihydroxyvitamin D3 response in mammary epithelial cells.

    PubMed

    Maund, Sophia L; Shi, Lihong; Cramer, Scott D

    2013-01-01

    Breast cancer is the most common non-cutaneous malignancy in American women, and better preventative strategies are needed. Epidemiological and laboratory studies point to vitamin D3 as a promising chemopreventative agent for breast cancer. Vitamin D3 metabolites induce anti-proliferative effects in breast cancer cells in vitro and in vivo, but few studies have investigated their effects in normal mammary epithelial cells. We hypothesized that 1,25(OH)2D3, the metabolically active form of vitamin D3, is growth suppressive in normal mouse mammary epithelial cells. In addition, we have previously established a role for the cytokine interleukin-1 alpha (IL1α) in the anti-proliferative effects of 1,25(OH)2D3 in normal prostate cells, and so we hypothesized that IL1α is involved in the 1,25(OH)2D3 response in mammary cells. Evaluation of cell viability, clonogenicity, senescence, and induction of cell cycle regulators p21 and p27 supported an anti-proliferative role for 1,25(OH)2D3 in mammary epithelial cells. Furthermore, 1,25(OH)2D3 increased the intracellular expression of IL1α, which was necessary for the anti-proliferative effects of 1,25(OH)2D3 in mammary cells. Together, these findings support the chemopreventative potential of vitamin D3 in the mammary gland and present a role for IL1α in regulation of mammary cell proliferation by 1,25(OH)2D3.

  14. A Role for Interleukin-1 Alpha in the 1,25 Dihydroxyvitamin D3 Response in Mammary Epithelial Cells

    PubMed Central

    Maund, Sophia L.; Shi, Lihong; Cramer, Scott D.

    2013-01-01

    Breast cancer is the most common non-cutaneous malignancy in American women, and better preventative strategies are needed. Epidemiological and laboratory studies point to vitamin D3 as a promising chemopreventative agent for breast cancer. Vitamin D3 metabolites induce anti-proliferative effects in breast cancer cells in vitro and in vivo, but few studies have investigated their effects in normal mammary epithelial cells. We hypothesized that 1,25(OH)2D3, the metabolically active form of vitamin D3, is growth suppressive in normal mouse mammary epithelial cells. In addition, we have previously established a role for the cytokine interleukin-1 alpha (IL1α) in the anti-proliferative effects of 1,25(OH)2D3 in normal prostate cells, and so we hypothesized that IL1α is involved in the 1,25(OH)2D3 response in mammary cells. Evaluation of cell viability, clonogenicity, senescence, and induction of cell cycle regulators p21 and p27 supported an anti-proliferative role for 1,25(OH)2D3 in mammary epithelial cells. Furthermore, 1,25(OH)2D3 increased the intracellular expression of IL1α, which was necessary for the anti-proliferative effects of 1,25(OH)2D3 in mammary cells. Together, these findings support the chemopreventative potential of vitamin D3 in the mammary gland and present a role for IL1α in regulation of mammary cell proliferation by 1,25(OH)2D3. PMID:24244740

  15. Vitamin D₃ metabolites enhance the NLRP3-dependent secretion of IL-1β from human THP-1 monocytic cells.

    PubMed

    Tulk, Sarah E; Liao, Kuo-Chieh; Muruve, Daniel A; Li, Yan; Beck, Paul L; MacDonald, Justin A

    2015-05-01

    Vitamin D3 has emerged as an important regulator of the immune system. With metabolic enzymes for vitamin D3 activation and vitamin D receptors (VDR) now identified in a variety of immune cells, the active vitamin D3 metabolite 1,25(OH)2D3, is thought to possess immunomodulatory properties. We examined whether 1,25(OH)2D3 might also enhance the NLRP3-dependent release of mature IL-1β from macrophages. PMA-differentiated THP-1 cells were stimulated with vitamin D3 metabolites and assessed for CYP27, CYP24, NLRP3, ASC, pro-caspase-1 expression by western blot and real-time qPCR as well as inflammasome activation with pro-inflammatory cytokine IL-1β release measured by ELISA. Exposure to 1,25(OH)2D3 had no effect on the basal expression levels of VDR; however, CYP27A1 transcript was suppressed and CYP24A1 transcript was substantively elevated. Both 1,25(OH)2D3 - and 25(OH)D3 induced IL-1β release from THP-1 cells, and these effects were blocked with application of the caspase-1 inhibitor YVAD and the NLRP3 inhibitors glyburide and Bay 11-7082. Interestingly, 1,25 (OH)2D3 exposure reduced NLRP3 protein expression but had no effect on ASC or pro-caspase-1 protein levels. The increase in mature IL-1β elicited by 1,25(OH)2D3 was modest compared to that found for ATP or C. difficile toxins. However, co-treatment of THP-1 cells with ATP and 1,25(OH)2D3 resulted in more IL-1β secretion than ATP or 1,25(OH)2D3 alone. PMID:25639477

  16. Vitamin D₃ metabolites enhance the NLRP3-dependent secretion of IL-1β from human THP-1 monocytic cells.

    PubMed

    Tulk, Sarah E; Liao, Kuo-Chieh; Muruve, Daniel A; Li, Yan; Beck, Paul L; MacDonald, Justin A

    2015-05-01

    Vitamin D3 has emerged as an important regulator of the immune system. With metabolic enzymes for vitamin D3 activation and vitamin D receptors (VDR) now identified in a variety of immune cells, the active vitamin D3 metabolite 1,25(OH)2D3, is thought to possess immunomodulatory properties. We examined whether 1,25(OH)2D3 might also enhance the NLRP3-dependent release of mature IL-1β from macrophages. PMA-differentiated THP-1 cells were stimulated with vitamin D3 metabolites and assessed for CYP27, CYP24, NLRP3, ASC, pro-caspase-1 expression by western blot and real-time qPCR as well as inflammasome activation with pro-inflammatory cytokine IL-1β release measured by ELISA. Exposure to 1,25(OH)2D3 had no effect on the basal expression levels of VDR; however, CYP27A1 transcript was suppressed and CYP24A1 transcript was substantively elevated. Both 1,25(OH)2D3 - and 25(OH)D3 induced IL-1β release from THP-1 cells, and these effects were blocked with application of the caspase-1 inhibitor YVAD and the NLRP3 inhibitors glyburide and Bay 11-7082. Interestingly, 1,25 (OH)2D3 exposure reduced NLRP3 protein expression but had no effect on ASC or pro-caspase-1 protein levels. The increase in mature IL-1β elicited by 1,25(OH)2D3 was modest compared to that found for ATP or C. difficile toxins. However, co-treatment of THP-1 cells with ATP and 1,25(OH)2D3 resulted in more IL-1β secretion than ATP or 1,25(OH)2D3 alone.

  17. The action spectrum for vitamin D3: initial skin reaction and prolonged exposure.

    PubMed

    van Dijk, Arjan; den Outer, Peter; van Kranen, Henk; Slaper, Harry

    2016-07-01

    Vitamin D3 photosynthesis in the skin is formulated as a set of reaction equations, including side-reactions to lumisterol, tachysterol and toxisterols, and the accompanying reverse reactions, isomerisation of previtamin D3 to vitamin D3 and photodegradation of vitamin D3. The solution of this set is given for the stationary irradiance spectrum. The effective action spectrum for the instantaneous vitamin D3 production changes shape as a function of exposure, and therefore, no single action spectrum can be used. We assessed the action spectrum for unexposed skin and for skin that has been exposed to 7.5 Standard Erythemal Doses (SED). We constructed two new estimates: (1) the RIVM action spectrum, based on absorption spectra, quantum yields and skin transmission spectra, and (2) the modified QUT action spectrum, which is adjusted for self-absorption and skin transmission. For previously unexposed skin, the modified QUT action spectrum gives a qualitatively similar, but larger estimate than the RIVM action spectrum. We have not been able to solve the lack of quantitative agreement between the vitamin D production estimates from the three action spectrum estimates (RIVM, modified QUT and CIE). All new action spectra have stronger emphasis on the short wavelengths than the CIE action spectrum. We showed that, for wavelengths larger than 300 nm, the bandwidth that was used in the experiment that formed the basis of the CIE action spectrum, gives a red-shift of about 1 nm. Generally, with the formation of previtamin D3, the return reaction to provitamin D3 limits the production of vitamin D3. After some exposure, the new action spectrum has negative values for the longer wavelengths in the UVB. For the RIVM action spectrum, this happens after 7.5 SED, for the modified QUT action spectrum already after 1.25 SED, and after 7.5 SED the net production rate is largely cancelled. Thus prolonged exposure of previously unexposed skin saturates vitamin D3 formation. For maximum

  18. 25-Hydroxyvitamin D3 Deficiency Independently Predicts Cognitive Impairment in Patients with Systemic Lupus Erythematosus

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  3. Calcitonin and vitamin D3 have high therapeutic potential for improving diabetic mandibular growth.

    PubMed

    Abbassy, Mona A; Watari, Ippei; Bakry, Ahmed S; Ono, Takashi; Hassan, Ali H

    2016-03-01

    The goal of this study was to assess the effect of the intermittent combination of an antiresorptive agent (calcitonin) and an anabolic agent (vitamin D3) on treating the detrimental effects of Type 1 diabetes mellitus (DM) on mandibular bone formation and growth. Forty 3-week-old male Wistar rats were divided into four groups: the control group (normal rats), the control C+D group (normal rats injected with calcitonin and vitamin D3), the diabetic C+D group (diabetic rats injected with calcitonin and vitamin D3) and the diabetic group (uncontrolled diabetic rats). An experimental DM condition was induced in the male Wistar rats in the diabetic and diabetic C+D groups using a single dose of 60 mg·kg(-1) body weight of streptozotocin. Calcitonin and vitamin D3 were simultaneously injected in the rats of the control C+D and diabetic C+D groups. All rats were killed after 4 weeks, and the right mandibles were evaluated by micro-computed tomography and histomorphometric analysis. Diabetic rats showed a significant deterioration in bone quality and bone formation (diabetic group). By contrast, with the injection of calcitonin and vitamin D3, both bone parameters and bone formation significantly improved (diabetic C+D group) (P < 0.05). These findings suggest that these two hormones might potentially improve various bone properties. PMID:27025264

  4. Calcitonin and vitamin D3 have high therapeutic potential for improving diabetic mandibular growth.

    PubMed

    Abbassy, Mona A; Watari, Ippei; Bakry, Ahmed S; Ono, Takashi; Hassan, Ali H

    2016-03-30

    The goal of this study was to assess the effect of the intermittent combination of an antiresorptive agent (calcitonin) and an anabolic agent (vitamin D3) on treating the detrimental effects of Type 1 diabetes mellitus (DM) on mandibular bone formation and growth. Forty 3-week-old male Wistar rats were divided into four groups: the control group (normal rats), the control C+D group (normal rats injected with calcitonin and vitamin D3), the diabetic C+D group (diabetic rats injected with calcitonin and vitamin D3) and the diabetic group (uncontrolled diabetic rats). An experimental DM condition was induced in the male Wistar rats in the diabetic and diabetic C+D groups using a single dose of 60 mg·kg(-1) body weight of streptozotocin. Calcitonin and vitamin D3 were simultaneously injected in the rats of the control C+D and diabetic C+D groups. All rats were killed after 4 weeks, and the right mandibles were evaluated by micro-computed tomography and histomorphometric analysis. Diabetic rats showed a significant deterioration in bone quality and bone formation (diabetic group). By contrast, with the injection of calcitonin and vitamin D3, both bone parameters and bone formation significantly improved (diabetic C+D group) (P < 0.05). These findings suggest that these two hormones might potentially improve various bone properties.

  5. Calcitonin and vitamin D3 have high therapeutic potential for improving diabetic mandibular growth

    PubMed Central

    Abbassy, Mona A; Watari, Ippei; Bakry, Ahmed S; Ono, Takashi; Hassan, Ali H

    2016-01-01

    The goal of this study was to assess the effect of the intermittent combination of an antiresorptive agent (calcitonin) and an anabolic agent (vitamin D3) on treating the detrimental effects of Type 1 diabetes mellitus (DM) on mandibular bone formation and growth. Forty 3-week-old male Wistar rats were divided into four groups: the control group (normal rats), the control C+D group (normal rats injected with calcitonin and vitamin D3), the diabetic C+D group (diabetic rats injected with calcitonin and vitamin D3) and the diabetic group (uncontrolled diabetic rats). An experimental DM condition was induced in the male Wistar rats in the diabetic and diabetic C+D groups using a single dose of 60 mg·kg−1 body weight of streptozotocin. Calcitonin and vitamin D3 were simultaneously injected in the rats of the control C+D and diabetic C+D groups. All rats were killed after 4 weeks, and the right mandibles were evaluated by micro-computed tomography and histomorphometric analysis. Diabetic rats showed a significant deterioration in bone quality and bone formation (diabetic group). By contrast, with the injection of calcitonin and vitamin D3, both bone parameters and bone formation significantly improved (diabetic C+D group) (P < 0.05). These findings suggest that these two hormones might potentially improve various bone properties. PMID:27025264

  6. Syntheses of 24R,25-dihydroxy-(6,19,19-3H)vitamin D3 and 24R,25-dihydroxy-(6,19,19-2H)vitamin D3

    SciTech Connect

    Yamada, S.; Shimizu, M.; Fukushima, K.; Niimura, K.; Maeda, Y. )

    1989-08-01

    24R,25-Dihydroxy-(6,19,19-3H)vitamin D3 with a specific activity of 54 Ci/mmol and 24R,25-dihydroxy-(6,19,19-2H)vitamin D3 with 2.6 deuterium atoms/mol were synthesized in four steps starting from 24R,25-Dihydroxyvitamin D3 via its sulfur dioxide adduct.

  7. Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor.

    PubMed

    Claro da Silva, Tatiana; Hiller, Christian; Gai, Zhibo; Kullak-Ublick, Gerd A

    2016-10-01

    Vitamin D3 regulates genes critical for human health and its deficiency is associated with an increased risk for osteoporosis, cancer, diabetes, multiple sclerosis, hypertension, inflammatory and immunological diseases. To study the impact of vitamin D3 on genes relevant for the transport and metabolism of nutrients and drugs, we employed next-generation sequencing (NGS) and analyzed global gene expression of the human-derived Caco-2 cell line treated with 500nM vitamin D3. Genes involved in neuropeptide signaling, inflammation, cell adhesion and morphogenesis were differentially expressed. Notably, genes implicated in zinc, manganese and iron homeostasis were largely increased by vitamin D3 treatment. An ∼10-fold increase in ceruloplasmin and ∼4-fold increase in haptoglobin gene expression suggested a possible association between vitamin D and iron homeostasis. SLC30A10, the gene encoding the zinc and manganese transporter ZnT10, was the chiefly affected transporter, with ∼15-fold increase in expression. SLC30A10 is critical for zinc and manganese homeostasis and mutations in this gene, resulting in impaired ZnT10 function or expression, cause manganese intoxication, with Parkinson-like symptoms. Our NGS results were validated by real-time PCR in Caco-2 cells, as well as in duodenal biopsies taken from healthy human subjects treated with 0.5μg vitamin D3 daily for 10 days. In addition to increasing gene expression of SLC30A10 and the positive control TRPV6, vitamin D3 also increased ZnT10 protein expression, as indicated by Western blot and cytofluorescence. In silico identification of potential vitamin D responsive elements (VDREs) in the 5'-flanking region of the SLC30A10 promoter and dual-luciferase reporter assay showed enhanced promoter activity in the presence of vitamin D receptor (VDR) and retinoid X receptor (RXR) constructs, as well as vitamin D3, but not when one of these factors was absent. Electrophoretic mobility shift assay (EMSA) and

  8. Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor.

    PubMed

    Claro da Silva, Tatiana; Hiller, Christian; Gai, Zhibo; Kullak-Ublick, Gerd A

    2016-10-01

    Vitamin D3 regulates genes critical for human health and its deficiency is associated with an increased risk for osteoporosis, cancer, diabetes, multiple sclerosis, hypertension, inflammatory and immunological diseases. To study the impact of vitamin D3 on genes relevant for the transport and metabolism of nutrients and drugs, we employed next-generation sequencing (NGS) and analyzed global gene expression of the human-derived Caco-2 cell line treated with 500nM vitamin D3. Genes involved in neuropeptide signaling, inflammation, cell adhesion and morphogenesis were differentially expressed. Notably, genes implicated in zinc, manganese and iron homeostasis were largely increased by vitamin D3 treatment. An ∼10-fold increase in ceruloplasmin and ∼4-fold increase in haptoglobin gene expression suggested a possible association between vitamin D and iron homeostasis. SLC30A10, the gene encoding the zinc and manganese transporter ZnT10, was the chiefly affected transporter, with ∼15-fold increase in expression. SLC30A10 is critical for zinc and manganese homeostasis and mutations in this gene, resulting in impaired ZnT10 function or expression, cause manganese intoxication, with Parkinson-like symptoms. Our NGS results were validated by real-time PCR in Caco-2 cells, as well as in duodenal biopsies taken from healthy human subjects treated with 0.5μg vitamin D3 daily for 10 days. In addition to increasing gene expression of SLC30A10 and the positive control TRPV6, vitamin D3 also increased ZnT10 protein expression, as indicated by Western blot and cytofluorescence. In silico identification of potential vitamin D responsive elements (VDREs) in the 5'-flanking region of the SLC30A10 promoter and dual-luciferase reporter assay showed enhanced promoter activity in the presence of vitamin D receptor (VDR) and retinoid X receptor (RXR) constructs, as well as vitamin D3, but not when one of these factors was absent. Electrophoretic mobility shift assay (EMSA) and

  9. Aortic calcification produced by vitamin D3 plus nicotine.

    PubMed

    Niederhoffer, N; Bobryshev, Y V; Lartaud-Idjouadiene, I; Giummelly, P; Atkinson, J

    1997-01-01

    Calcification of the elastic arteries of the young rat by treatment with vitamin D and nicotine (VDN) has been proposed as an animal model of arterial calcification associated with age and age-related vascular pathology in man. The calcium-binding protein, S-100, which is found in human atherosclerotic lesions was associated with medial calcification of the aorta in VDN rats, especially in cases of severe calcification. Calcification (total calcium content: 366 +/- 87, n = 12 in VDN vs. 24 +/- 2 micromol g(-1) aortic dry weight in controls, n = 13) involved elastocalcinosis leading to elastolysis as revealed by a fall in the amount of desmosine and isodesmosine in the aortic wall (266 +/- 17 and 254 +/- 15 in VDN vs. 655 +/- 56 and 588 +/- 30 microg g(-1) aortic dry weight in controls). The decrease in elastin was associated with an increase in the stiffness of the aortic wall (elastic modulus: 15.1 +/- 1.8 in VDN vs. 6.7 +/- 0.5 10(6) dyn cm(-2) in controls), an increase in end-systolic stress (central systolic aortic pressure: 152 +/- 6 in VDN vs. 136 +/- 2 mm Hg in controls) (at a normotensive mean pressure level) and left ventricular hypertrophy (heart weight/body weight 2.51 +/- 0.10 in VDN vs. 2.24 +/- 0.07 g kg(-1) in controls). In conclusion, the mechanisms and consequences of aortic calcification in VDN show several similarities with calcification occurring in human athero- and arteriosclerosis.

  10. Variability of pre-vitamin D3 effectiveness of UV appliances for skin tanning.

    PubMed

    Sayre, Robert M; Dowdy, John C; Shepherd, James G

    2010-07-01

    While there is limited documentation that certain indoor tanning lamps effectively produce vitamin D, the diversity of such devices has not been extensively surveyed. This study compares the spectral effectiveness of a variety of tanning units, and solar spectra, for ultraviolet (UV) photosynthesis of pre-vitamin D3 (preD3) and UV induced erythema. Well-established techniques exist for the calculation of spectral effectiveness for photobiological responses that have defined action spectra. Using spectroradiometric data from sunlamp measurements, and standard solar reference spectra, we computed effective irradiances using the CIE action spectrum for the production of preD3 in human skin and the ISO/CIE human erythema reference action spectrum. We found, as with sunlight at different times or latitude, the preD3 and erythemal effectiveness of sunlamps varied as a function of the UV-B proportion of the spectrum. Ratios of sunlamp preD3 to erythemal effectiveness ranged from approximately 0.5 to nearly 2.0, similar to ratios for sunlight. Optimal risk to benefit conditions for preD3 from solar UV exposure occurs under high solar altitude, low zenith angle, midday midsummer sunlight. Analogous optimal preD3 exposure conditions are provided by low to intermediate pressure sunlamps with greater UV-B spectral overlap with the preD3 action spectrum. Similar to low altitude or high latitude sunlight, high pressure tanning units, filtered for negligible UV-B emissions, have insignificant vitamin D benefit. We conclude that while vitamin D can be made by both UVB exposure from indoor tanning units and by exposure UVB from sunlight, the effect is also comparably variable. Unlike sunlight, indoor tanning offers privacy and environmental conditions for practical full body exposure, lowering the requisite exposure per skin surface area, and device timers limit the potential of overexposure. Guidance for optimal use of tanning sources for vitamin D benefit is needed.

  11. Autocrine TGFbeta signaling mediates vitamin D3 analog-induced growth inhibition in breast cells.

    PubMed

    Yang, L; Yang, J; Venkateswarlu, S; Ko, T; Brattain, M G

    2001-09-01

    In this study, we address whether TGFbeta signaling mediates vitamin D3 analog-induced growth inhibition in nonmalignant and malignant breast cells. Normal mammary epithelial cells (184), immortalized nonmalignant mammary epithelial cells (184A1 and MCF10A), and breast cancer cells (early passage MCF7: MCF7E) were sensitive to the inhibitory effects of vitamin D3 analogs (EB1089 and MC1288) while late passage MCF7 breast cancer (MCF7L) cells were relatively resistant. A similar pattern of sensitivity to TGFbeta was observed with these cells. Thus, the sensitivity to the vitamin D3 analogs correlated with the sensitivity to TGFbeta. MCF7L TGFbetaRII-transfected cells, which have autocrine TGFbeta activity, were more sensitive to EB1089 than MCF7L cells. TGFbeta neutralizing antibody was found to block the inhibitory effects of these analogs. These results are consistent with the idea that autocrine TGFbeta signaling mediates the anti-proliferative effects of the vitamin D3 analogs in these cells. The expression of TGFbeta isoforms and/or TGFbeta receptors was induced by the analogs in the vitamin D3 and TGFbeta sensitive cells. Vitamin D3 analogs did not induce TGFbeta or TGFbeta receptor expression in the resistant MCF7L cells. Therefore, EB1089 induces autocrine TGFbeta activity through increasing expression of TGFbeta isoforms and/or TGFbeta receptors. In addition, EB1089 induced nuclear VDR protein levels in the sensitive 184A1 cells but not in the resistant MCF7L cells. 184A1 cells were more sensitive to EB1089-induced VDR-dependent transactivation than MCF7L cells as measured by a luciferase reporter construct containing the VDRE, indicating a defect of VDR signaling in MCF7L cells. Smad3, a TGFbeta signaling mediator, coactivated VDR-dependent transactivation in 184A1 cells but not in MCF7L cells. These results indicate that Smad3 coactivates VDR to further enhance TGFbeta signaling and vitamin D3 signaling in the sensitive 184A1 cells. The results also

  12. Intestinal absorption of triglyceride and vitamin D3 in aged and young rats

    SciTech Connect

    Holt, P.R.; Dominguez, A.A.

    1981-12-01

    (3H)Trioleyl glycerol (TO) and (14C)vitamin D3 were perfused intraduodenally for 5 hr in aged (19-21 months) and young adult (4-5 months) Sprague-Dawley rats. The rate of intestinal uptake from the gastrointestinal lumen and transport into the body of these lipids were decreased in the aged animals. Since the distribution of TO lipolytic products in the lumen was unchanged, reduced intestinal uptake rate probably occurred at the mucosal membrane. Furthermore, in the aged rats, the rate of transintestinal transport of both trioleyl glycerol and vitamin D3 was impaired. No evidence for impaired mucosal TO reesterification or for accumulation of vitamin D3 metabolites was found, suggesting that intestinal lipid accumulation resulted from a defect in lipoprotein assembly or in discharge from the mucosal cell. Impaired absorption of lipids may contribute to malnutrition and osteopenia of advancing age.

  13. The inhibitory kinetics and mechanism of dietary vitamins D3 and B2 on xanthine oxidase.

    PubMed

    Lin, Suyun; Zhang, Guowen; Liao, Yijing; Gong, Deming

    2016-06-15

    Dietary guidelines to promote health are usually based on the patterns' prediction on disease risk of foods and nutrients. Overactivity of xanthine oxidase (XO) is the underlying cause of gout. Herein, the inhibitory kinetics and mechanism of dietary vitamins D3 and B2 on XO were investigated by multispectroscopic methods and a molecular modeling technique. The results showed that vitamin D3 competitively inhibited XO with an inhibition constant of 26.93 ± 0.42 μM by inserting into the active cavity of XO interacting with the surrounding amino acid residues through hydrogen bond and van der Waals forces. Vitamin D3 bound to XO thereby induced the structural compactness of XO which in turn hindered the binding of substrate xanthine to cause the inhibition on XO. Vitamin B2 exhibited a mixed-type inhibition by binding to the vicinity of the active cavity with an inhibition constant of 37.76 ± 0.87 μM through hydrophobic interactions and a feeble hydrogen bond, and it induced the unfolding of the XO structure and an increase of the flexible loops (β-turns and random coils) which might move to cover the active pocket and reduce the binding of the substrate xanthine, and then lead to a lower catalytic activity of the enzyme. In addition, vitamins D3 and B2 showed a synergistic effect on inhibiting the activity of XO in a certain range of concentration. These findings may provide new insights into the inhibitory mechanism of vitamins D3 and B2 on XO and functional research of the vitamins in the supplementary treatment of gout.

  14. The inhibitory kinetics and mechanism of dietary vitamins D3 and B2 on xanthine oxidase.

    PubMed

    Lin, Suyun; Zhang, Guowen; Liao, Yijing; Gong, Deming

    2016-06-15

    Dietary guidelines to promote health are usually based on the patterns' prediction on disease risk of foods and nutrients. Overactivity of xanthine oxidase (XO) is the underlying cause of gout. Herein, the inhibitory kinetics and mechanism of dietary vitamins D3 and B2 on XO were investigated by multispectroscopic methods and a molecular modeling technique. The results showed that vitamin D3 competitively inhibited XO with an inhibition constant of 26.93 ± 0.42 μM by inserting into the active cavity of XO interacting with the surrounding amino acid residues through hydrogen bond and van der Waals forces. Vitamin D3 bound to XO thereby induced the structural compactness of XO which in turn hindered the binding of substrate xanthine to cause the inhibition on XO. Vitamin B2 exhibited a mixed-type inhibition by binding to the vicinity of the active cavity with an inhibition constant of 37.76 ± 0.87 μM through hydrophobic interactions and a feeble hydrogen bond, and it induced the unfolding of the XO structure and an increase of the flexible loops (β-turns and random coils) which might move to cover the active pocket and reduce the binding of the substrate xanthine, and then lead to a lower catalytic activity of the enzyme. In addition, vitamins D3 and B2 showed a synergistic effect on inhibiting the activity of XO in a certain range of concentration. These findings may provide new insights into the inhibitory mechanism of vitamins D3 and B2 on XO and functional research of the vitamins in the supplementary treatment of gout. PMID:27241164

  15. Low-calcium diets increase both production and clearance of 1,25-dihydroxyvitamin D3 in rats

    SciTech Connect

    Fox, J.; Bunker, J.E.; Kamimura, M.; Wong, P.F. )

    1990-02-01

    Administration of large doses of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to animals induces 1,25(OH)2D3 side-chain oxidative pathways. This study determined if the elevated plasma 1,25(OH)2D3 seen in rats fed low-Ca diets is associated not only with an increased production rate (PR) but also with an increased metabolic clearance rate (MCR) of the hormone. In vitamin D-replete rats fed a Ca-deficient diet for 3-4 wk, the PR increased 21-fold, plasma levels 15-fold, and the MCR by 37%. The increased MCR in Ca-deficient rats was associated with a 48% increase in hepatic microsomal UDP glucuronyl transferase enzyme activity, whereas 1,25(OH)2D3 catabolism by homogenates of liver and small intestinal mucosa was unchanged. In contrast to the effects of low-Ca diets, acute (7 h) pharmacological elevation of plasma 1,25(OH)2D3 to 1.5 ng/ml in normal rats did not influence the MCR. Thus chronically elevated 1,25(OH)2D3 levels are necessary to stimulate clearance. In conclusion, 1,25(OH)2D3 clearance in rats can be stimulated not only by chronic pharmacological doses of 1,25(OH)2D3 but also by the physiological stimulus of a low-Ca diet. Hence, plasma 1,25(OH)2D3 levels can be regulated by changes in both PR and MCR.

  16. Vitamin D3 Supplemental Treatment for Mania in Youth with Bipolar Spectrum Disorders

    PubMed Central

    Sikoglu, Elif M.; Navarro, Ana A. Liso; Starr, Debra; Dvir, Yael; Nwosu, Benjamin Udoka; Czerniak, Suzanne M.; Rogan, Ryan C.; Castro, Martha C.; Edden, Richard A. E.; Frazier, Jean A.

    2015-01-01

    Abstract Objective: We aimed to determine the effect of an open-label 8 week Vitamin D3 supplementation on manic symptoms, anterior cingulate cortex (ACC) glutamate, and γ-aminobutyric acid (GABA) in youth exhibiting symptoms of mania; that is, patients with bipolar spectrum disorders (BSD). We hypothesized that an 8 week Vitamin D3 supplementation would improve symptoms of mania, decrease ACC glutamate, and increase ACC GABA in BSD patients. Single time point metabolite levels were also evaluated in typically developing children (TD). Methods: The BSD group included patients not only diagnosed with BD but also those exhibiting bipolar symptomology, including BD not otherwise specified (BD-NOS) and subthreshold mood ratings (Young Mania Rating Scale [YMRS] ≥8 and Clinical Global Impressions - Severity [CGI-S] ≥3). Inclusion criteria were: male or female participants, 6–17 years old. Sixteen youth with BSD exhibiting manic symptoms and 19 TD were included. BSD patients were asked to a take daily dose (2000 IU) of Vitamin D3 (for 8 weeks) as a supplement. Neuroimaging data were acquired in both groups at baseline, and also for the BSD group at the end of 8 week Vitamin D3 supplementation. Results: Baseline ACC GABA/creatine (Cr) was lower in BSD than in TD (F[1,31]=8.91, p=0.007). Following an 8 week Vitamin D3 supplementation, in BSD patients, there was a significant decrease in YMRS scores (t=−3.66, p=0.002, df=15) and Children's Depression Rating Scale (CDRS) scores (t=−2.93, p=0.01, df=15); and a significant increase in ACC GABA (t=3.18, p=0.007, df=14). Conclusions: Following an 8 week open label trial with Vitamin D3, BSD patients exhibited improvement in their mood symptoms in conjunction with their brain neurochemistry. PMID:26091195

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

    PubMed

    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. PMID:27291692

  18. Polymorphism of 14C vitamin D3 binding protein in cattle and water buffalo serum.

    PubMed

    Masina, P; Ramunno, L; Iannelli, D

    1978-01-01

    Cattle and water buffalo sera labelled with vitamin D3[14C] (300 and 480 individual samples respectively) were subjected to starch gel electrophoresis followed by autoradiography in an attempt to identify a possible polymorphism of the proteins capable of binding this vitamin. Three phenotypes controlled by two codominant autosomal alleles were identified in cattle while in water buffalo six phenotypes controlled by three codominant autosomal alleles were observed.

  19. Response of keloid fibroblasts to Vitamin D3 and quercetin treatment - in vitro study.

    PubMed

    Mathangi Ramakrishnan, K; Babu, M; Lakshmi Madhavi, M S

    2015-09-30

    Keloid scars continue to pose a challenge to clinicians as the treatment armamentarium lacks a formidable agent to tackle them. We have undertaken an in vitro study based on the mechanism of action of Vitamin D3 and quercetin on isolated keloid fibroblasts. Dose-dependent action on the reduction of cellular proliferation, collagen synthesis and induction of apoptosis by Vitamin D3 and quercetin are analyzed and probable mechanism of action is elaborated. This study thus opens up newer avenues in tackling keloid scars effectively. PMID:27279805

  20. Response of keloid fibroblasts to Vitamin D3 and quercetin treatment - in vitro study

    PubMed Central

    Mathangi Ramakrishnan, K.; Babu, M.; Lakshmi Madhavi, M.S.

    2015-01-01

    Summary Keloid scars continue to pose a challenge to clinicians as the treatment armamentarium lacks a formidable agent to tackle them. We have undertaken an in vitro study based on the mechanism of action of Vitamin D3 and quercetin on isolated keloid fibroblasts. Dose-dependent action on the reduction of cellular proliferation, collagen synthesis and induction of apoptosis by Vitamin D3 and quercetin are analyzed and probable mechanism of action is elaborated. This study thus opens up newer avenues in tackling keloid scars effectively. PMID:27279805

  1. In vivo activation of the intracrine vitamin D pathway in innate immune cells and mammary tissue during a bacterial infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is an important regulator of immune function. The enzyme that synthesizes 1,25(OH)2D3 from 25-hydroxyvitamin D3 is 1alpha-hydroxylase (1alpha-OHase; CYP27B1). Several in vitro studies have shown that TLR signaling induces expre...

  2. Evolutionary importance for the membrane enhancement of the production of vitamin D3 in the skin of poikilothermic animals.

    PubMed

    Holick, M F; Tian, X Q; Allen, M

    1995-04-11

    The photoproduction of vitamin D in the skin was essential for the evolutionary development of terrestrial vertebrates. During exposure to sunlight, previtamin D3 formed in the skin is isomerized to vitamin D3 (calciol) by a temperature-dependent process. Since early land vertebrates were poikilothermic, the relatively slow conversion of previtamin D3 to vitamin D3 at ambient temperature put them at serious risk for developing vitamin D deficiency, thus leading to a poorly mineralized skeleton that could have ultimately halted further evolutionary development of vertebrates on land. We evaluated the rate of isomerization of previtamin D3 to vitamin D3 in the skin of iguanas and found the isomerization rate was enhanced by 1100% and 1700% at 25 degrees C and 5 degrees C, respectively. It is likely that the membrane entrapment of previtamin D3 in its s-cis,s-cis conformation is responsible for the markedly enhanced conversion of previtamin D3 to vitamin D3. The membrane-enhanced production of vitamin D3 ensures the critical supply of vitamin D3 to poikilothermic animals such as iguanas.

  3. Effects of vitamin D3 stimulation of thioredoxin-interacting protein in hepatocellular carcinoma

    PubMed Central

    Hamilton, James P.; Potter, James J.; Koganti, Lahari; Meltzer, Stephen J.; Mezey, Esteban

    2014-01-01

    Aim Thioredoxin-interacting protein (TXNIP) promotes oxidative stress by inactivating thioredoxin (TXN). This protein is involved in diverse disease processes, including insulin resistance, atherosclerosis and carcinogenesis. The aim of the present study was to measure the expression and function of TXNIP in in vitro models of liver disease, as well as in primary human hepatocellular carcinoma (HCC) tissue specimens. In addition, we wanted to determine the effects of vitamin D3-induced TXNIP stimulation in HCC-derived cell lines. Methods TXNIP expression was measured by quantitative reverse transcription polymerase chain reaction and western blots. TXNIP expression was stimulated by vitamin D exposure and by transfection. Cell proliferation, apoptosis and reactive oxygen species were determined by standard assays. Results TXNIP expression levels were low in HCC cell lines, and vitamin D3 stimulated TXNIP expression in vitro. In HCC cells transfected with a TXNIP expression vector or treated with exogenous vitamin D3, there was a reduction in cell proliferation and an increase in apoptosis. Cells expressing TXNIP were markedly susceptible to oxidative injury induced by cobalt chloride or bacterial lipopolysaccharide. TXNIP expression was reduced or absent in a majority of primary human HCC specimens relative to matching, non-cancerous liver tissue. Conclusion TXNIP expression is low or absent in human HCC specimens and HCC-derived cell lines. Vitamin D3 stimulates TXNIP expression, resulting in diminished proliferation and enhanced apoptosis. Liver cells expressing TXNIP are primed for oxidative injury. These findings suggest that stimulation of TXNIP expression, by factors such as vitamin D3, may attenuate carcinogenesis in patients with chronic liver disease. PMID:24451003

  4. Vitamin D Metabolism and Action in Human Marrow Stromal Cells: Effects of Chronic Kidney Disease

    PubMed Central

    Zhou, Shuanhu; LeBoff, Meryl S.; Waikar, Sushrut S.; Glowacki, Julie

    2012-01-01

    Human marrow stromal cells (hMSCs) are targets of 1! ,25-dihydroxyvitamin D [1! ,25(OH)2D3] action to promote their differentiation to osteoblasts, but they also participate in vitamin D metabolism by converting 25-dihydroxyvitamin D3 [25(OH)D3] to 1! ,25(OH)2D3 by 1α-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is associated with impaired renal biosynthesis of 1! ,25(OH)2D, low bone mass, and increased fracture risk. We tested whether CKD influences hMSCs' responses to vitamin D3 metabolites. The hMSCs were obtained from tissues discarded during arthroplasty for hip osteoarthrosis, including a subject who had been undergoing hemodialysis for 2+ years. There was a significant positive correlation between in vitro stimulation of osteoblastogenesis (alkaline phosphatase activity) by 1! ,25(OH)2D3 and subjects' estimated glomerular filtration rate (eGFR, r=0.47, p=0.015, n=26, 56–83 years of age). Osteoblastogenesis was stimulated in hMSCs from both the hemodialysis and control subjects by 1! ,25(OH)2D3 (10 ! M), 25(OH)D3 (100 ! M), or D3 (1000 ! M). Thus, vitamin D metabolism may play an autocrine/paracrine role in osteoblast differentiation of hMSCs. These findings suggest that in CKD patients 25(OH)D-sufficiency may play an important role in skeletal health; osteoblastic bone formation in CKD patients may not be optimal unless there is sufficient serum 25(OH)D substrate for the MSCs to synthesize and respond to local 1! ,25(OH)2D. PMID:22989482

  5. Safety and Efficacy of High-dose Daily Vitamin D3 Supplementation in Children and Young Adults With Sickle Cell Disease.

    PubMed

    Dougherty, Kelly A; Bertolaso, Chiara; Schall, Joan I; Smith-Whitley, Kim; Stallings, Virginia A

    2015-07-01

    Suboptimal vitamin D (vit D) status (<32 ng/mL) is ubiquitous among African American children with type SS sickle cell disease (SCD-SS). The vit D supplemental dose to normalize vit D status is unknown. Five to 20-year-old African American children with (n=21) and without (n=23) SCD-SS were randomized to vit D3 supplementation (4000 or 7000 IU/d) and evaluated at 6 and 12 weeks for changes in vit D and SCD status. A dose was considered unsafe if serum calcium was elevated associated with elevated serum 25 hydroxyvitamin D (25(OH)D). At baseline 95% of subjects with SCD-SS and 87% of healthy controls had suboptimal vit D status (mean±SD, 19.2±7.2 and 22.3±9.3 ng/mL, respectively). After 12 weeks supplementation, both D3 doses were safe and well tolerated. Neither group achieved the a priori efficacy criterion of 25(OH)D≥32 ng/mL in >80% of subjects (45% in SCD-SS and 63% in controls). However, for both subjects with SCD-SS and healthy subjects by 12 weeks, deficient (<20 ng/mL) vit D status was eliminated only in those receiving 7000 IU/d. For subjects with SCD-SS, by 12 weeks there was a significant (all P<0.05) increase in fetal hemoglobin, decrease in high-sensitivity C-reactive protein, and reduction in the percentage of subjects with a high platelet count.

  6. Differential skeletal responses of hindlimb unloaded rats on a vitamin D-deficient diet to 1,25-dihydroxyvitamin D3 and its analog, seocalcitol (EB1089)

    NASA Technical Reports Server (NTRS)

    Narayanan, Ramesh; Allen, Matthew R.; Gaddy, Dana; Bloomfield, Susan A.; Smith, Carolyn L.; Weigel, Nancy L.

    2004-01-01

    Conditions of disuse in bed rest patients, as well as microgravity experienced by astronauts are accompanied by reduced mechanical loading, reduced calcium absorption, and lower serum levels of 1,25(OH)2D3 (1,25-D), the active metabolite of vitamin D, all contributing to bone loss. To determine whether 1,25-D or a less calcemic analog, Seocalcitol or EB1089 (1 alpha,25-dihydroxy-22,24-diene-24,26,27-trihomovitamin D3) can alleviate bone loss in a rat hindlimb unloading model of disuse osteopenia, mature male rats originally on a vitamin D replete diet containing 1.01% calcium were transferred to a vitamin D-deficient diet containing 0.48% calcium and then tail suspended and treated for 28 days with vehicle, 0.05 microg/kg 1,25-D, or 0.05 microg/kg EB1089. The vitamin D-deficient diet caused a substantial decrease in bone mineral density (-8%), which may be compounded by hindlimb unloading (-10%). Exogenous 1,25-D not only prevented the bone loss but also increased the bone mineral density to greater than the baseline level (+7%). EB1089 was less effective in preventing bone loss. Analysis of site and cell-specific effects of 1,25-D and EB1089 revealed that 1,25-D was more active than EB1089 in the intestine, the site of calcium absorption, and in inducing osteoclastogenesis and bone resorption whereas EB1089 was more effective in inducing osteoblast differentiation. These studies suggest that elevating circulating 1,25-D levels presumably increasing calcium absorption can counteract bone loss induced by disuse or microgravity with its associated reductions in circulating 1,25-D and decreased calcium absorption.

  7. Effects of vitamin D2 or D3 supplementation on glycaemic control and cardiometabolic risk among people at risk of type 2 diabetes: results of a randomized double‐blind placebo‐controlled trial

    PubMed Central

    Menon, R. K.; Sharp, S. J.; Mannan, N.; Timms, P. M.; Martineau, A. R.; Rickard, A. P.; Boucher, B. J.; Chowdhury, T. A.; Griffiths, C. J.; Greenwald, S. E.; Griffin, S. J.; Hitman, G. A.

    2016-01-01

    Aims To investigate the effect of short‐term vitamin D supplementation on cardiometabolic outcomes among individuals with an elevated risk of diabetes. Methods In a double‐blind placebo‐controlled randomized trial, 340 adults who had an elevated risk of type 2 diabetes (non‐diabetic hyperglycaemia or positive diabetes risk score) were randomized to either placebo, 100 000 IU vitamin D2 (ergocalciferol) or 100 000 IU vitamin D3 (cholecalciferol), orally administered monthly for 4 months. The primary outcome was change in glycated haemoglobin (HbA1c) between baseline and 4 months, adjusted for baseline. Secondary outcomes included: blood pressure; lipid levels; apolipoprotein levels; C‐reactive protein levels; pulse wave velocity (PWV); anthropometric measures; and safety of the supplementation. Results The mean [standard deviation (s.d.)] 25‐hydroxyvitamin D [25(OH)D]2 concentration increased from 5.2 (4.1) to 53.9 (18.5) nmol/l in the D2 group, and the mean (s.d.) 25(OH)D3 concentration increased from 45.8 (22.6) to 83.8 (22.7) nmol/l in the D3 group. There was no effect of vitamin D supplementation on HbA1c: D2 versus placebo: −0.05% [95% confidence interval (CI) −0.11, 0.02] or −0.51 mmol/mol (95% CI −1.16, 0.14; p = 0.13); D3 versus placebo: 0.02% (95% CI −0.04, 0.08) or 0.19 mmol/mol (95% CI −0.46, 0.83; p = 0.57). There were no clinically meaningful effects on secondary outcomes, except PWV [D2 versus placebo: −0.68 m/s (95% CI −1.31, −0.05); D3 versus placebo −0.73 m/s (95% CI −1.42, −0.03)]. No important safety issues were identified. Conclusions Short‐term supplementation with vitamin D2 or D3 had no effect on HbA1c. The modest reduction in PWV with both D2 and D3 relative to placebo suggests that vitamin D supplementation has a beneficial effect on arterial stiffness. PMID:26700109

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

    PubMed

    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. PMID:19555772

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

    PubMed

    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.). PMID:21430919

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

    PubMed

    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.

  11. Voltammetric determination of vitamin D3 with a rotating glassy carbon electrode.

    PubMed

    Hernández Méndez, J; Sánchez Pérez, A; Delgado Zamarreño, M; Hernández Garcia, M L

    1988-01-01

    A voltamperometric study (DC and DP) on the electroanalytical behaviour of vitamin D(3) in a methanolic solution using LiClO(4) as the supporting electrolyte and working with a glassy carbon electrode was carried out. Vitamin D(3) exhibits an oxidation wave (DC) or peak (DP) at potentials close to +1.1 V (versus SCE). The optimum experimental conditions for the best reproducibility of the voltamperometric signal were determined and the different parameters affecting the electrochemical process were studied. The electrochemical process was seen to be irreversible and, under certain conditions, adsorption of vitamin D(3) onto the electrode surface was observed. A voltamperometric procedure for the determination of vitamin D(3) in a concentration range of 2 x 10(-6) - 2 x 10(-4) M is proposed. The detection limit is of the order of 2 x 10(-6) M and the relative standard deviations are 1.1% (DC) and 2.6% (DP), respectively.

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

    PubMed

    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.).

  13. Formulation of Nanoliposomal Vitamin D3 for Potential Application in Beverage Fortification

    PubMed Central

    Mohammadi, Maryam; Ghanbarzadeh, Babak; Hamishehkar, Hamed

    2014-01-01

    Purpose: Vitamin D, a liposoluble vitamin has many benefits on health. Encapsulation of bioactives in lipid-based carrier systems like nanoliposomes preserves their native properties against oxidation over time along with providing its stable aqueous dispersion. Methods: In the current study, vitamin D3 nanoliposomes were prepared using thin-film hydration-sonication method and fully characterized by different instrumental techniques. Results: According to FTIR and DSC results, no interaction was observed between encapsulated nutraceutical and liposome constituents. The particle size and size distribution (Span value) were calculated 82–90 nm and 0.70–0.85, respectively. TEM analysis showed nano sized globular and bilayer vesicles. In all formations, the encapsulation efficiency of vitamin D3 was calculated more than 93%. Addition of cholesterol to lecithin bilayer increased the negative zeta potential from -29 to -43mV. Conclusion: The results of this study concluded that the liposomal nanoparticles may be introduced as a suitable carrier for fortification of beverages with vitamin D3. PMID:25671191

  14. Vitamin D3 Supplementation and Childhood Diarrhea: A Randomized Controlled Trial

    PubMed Central

    Maroof, Zabihullah; Chandramohan, Daniel; Bruce, Jane; Mughal, M. Zulf; Bhutta, Zulfiqar; Walraven, Gijs; Masher, Mohammad I.; Ensink, Jeroen H.J.; Manaseki-Holland, Semira

    2013-01-01

    OBJECTIVE: To investigate the effect of vitamin D3 supplementation on the incidence and risk for first and recurrent diarrheal illnesses among children in Kabul, Afghanistan. METHODS: This double-blind placebo-controlled trial randomized 3046 high-risk 1- to 11-month-old infants to receive 6 quarterly doses of oral vitamin D3 (cholecalciferol 100 000 IU) or placebo in inner city Kabul. Data on diarrheal episodes (≥3 loose/liquid stools in 24 hours) was gathered through active and passive surveillance over 18 months of follow-up. Time to first diarrheal illness was analyzed by using Kaplan-Meier plots. Incidence rates and hazard ratios (HRs) were calculated by using recurrent event Poisson regression models. RESULTS: No significant difference existed in survival time to first diarrheal illness (log rank P = .55). The incidences of diarrheal episodes were 3.43 (95% confidence interval [CI], 3.28–3.59) and 3.59 per child-year (95% CI, 3.44–3.76) in the placebo and intervention arms, respectively. Vitamin D3 supplementation was found to have no effect on the risk for recurrent diarrheal disease in either intention-to-treat (HR, 1.05; 95% CI, 0.98–1.17; P = .15) or per protocol (HR, 1.05; 95% CI, 0.98–1.12; P = .14) analyses. The lack of preventive benefit remained when the randomized population was stratified by age groups, nutritional status, and seasons. CONCLUSIONS: Quarterly supplementation with vitamin D3 conferred no reduction on time to first illness or on the risk for recurrent diarrheal disease in this study. Similar supplementation to comparable populations is not recommended. Additional research in alternative settings may be helpful in elucidating the role of vitamin D3 supplementation for prevention of diarrheal diseases. PMID:24019420

  15. Vitamin D status in Egyptian patients with juvenile-onset systemic lupus erythematosus.

    PubMed

    Garf, Kamal El; Marzouk, Huda; Farag, Yomna; Rasheed, Laila; Garf, Ayman El

    2015-09-01

    There are scanty data on the prevalence of vitamin D deficiency and its relation to disease activity among patients with juvenile-onset systemic lupus erythematosus (JoSLE) in the Middle East and North Africa, an area known to be endemic for vitamin D deficiency and insufficiency. The aim of this study was, therefore, to study vitamin D status and its relation to disease activity and parameters in Egyptian patients with JoSLE. Serum levels of 25(OH) D3 in 70 JoSLE patients were compared to 40 age-, sex-, and body mass index-matched healthy controls. The 25(OH) D3 was determined by enzyme-linked immunosorbent assay. Information regarding the medical history, clinical symptoms, and signs was registered at the time of serum sampling. Disease activity of SLE was evaluated according to the SLEDAI score. The mean level of serum 25(OH) D3 was 12 ± 3.7 in JoSLE patients compared to 21 ± 3.5 ng/mL in normal controls (p < 0.001). Forty percent (28/70) of the JoSLE patients has severe 25(OH) D3 deficiency (≤10 ng/mL), and 60 % of the JoSLE patients has 25(OH) D3 insufficiency (≤30 ng/mL). None of the JoSLE patients has 25(OH) D3 level >30 ng/mL. There was no significant correlation between serum levels of 25(OH) D3 and the demographic data, medication used, and some laboratory data of patients with JoSLE. Disease activity score in our patients was insignificantly correlated with serum levels of 25(OH) D3. In spite of vitamin D supplementation in Egyptian JoSLE patients and the presence of vitamin D insufficiency in the control group, there are still significantly lower levels of vitamin D in JoSLE compared to normal controls.

  16. Redox regulation of cAMP levels by ascorbate in 1,25-dihydroxy- vitamin D3-induced differentiation of HL-60 cells.

    PubMed Central

    López-Lluch, G; Burón, M I; Alcaín, F J; Quesada, J M; Navas, P

    1998-01-01

    1alpha,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] induces differentiation to monocyte-macrophage lineage of several leukaemic cell lines such as HL-60, U937, M1 and Mono Mac 6. Ascorbate also modulates growth and differentiation of different animal cells in culture. We have previously reported the stimulating effect of ascorbate on 1, 25-(OH)2D3-induced HL-60 cell differentiation. We show here that 1, 25-(OH)2D3 induces a transient increase in cAMP levels in these cells, and ascorbate significantly increases these cAMP levels. Ascorbate alone does not have any effect. Other cAMP-increasing agents such as isobutylmethylxanthine, forskolin and prostaglandin E2 maintain high levels of cAMP at 48 h of incubation and also enhance differentiation along the monocytic pathway induced by 1, 25-(OH)2D3, as revealed by specific differentiation markers, demonstrating the importance of cAMP in the differentiation process. It is also shown that the presence of ascorbate and its free radical (AFR) during 1,25-(OH)2D3-induced differentiation significantly decreases cytoplasmic NADH levels compared with those induced by 1,25-(OH)2D3 in HL-60 cells. The results indicate that NADH is an inhibitor of adenylate cyclase in these cells. AFR is an electron acceptor of the trans-plasma-membrane electron-transport system, and NADH is the electron donor. Through this system, ascorbate and AFR keep levels of NADH low, thereby decreasing its inhibitory effect on adenylate cyclase activity and so increasing cAMP synthesis. We also demonstrate that other ascorbate derivatives, such as ascorbate 2-phosphate and dehydroascorbate, both of which are unable to produce AFR, do not alter intracellular NADH levels during 1, 25-(OH)2D3-induced differentiation. Also, ascorbate and AFR increase specific differentiation markers (CD14 and NitroBlue Tetrazolium reduction) but neither ascorbate 2-phosphate nor dehydroascorbate show this enhancing activity. In summary, we propose that the effect of ascorbate on 1,25

  17. High serum vitamin D levels reduce the risk for nonalcoholic fatty liver disease in healthy men independent of metabolic syndrome.

    PubMed

    Rhee, Eun-Jung; Kim, Mee Kyoung; Park, Se Eun; Park, Cheol-Young; Baek, Ki Hyun; Lee, Won-Young; Kang, Moo Il; Park, Sung-Woo; Kim, Sun-Woo; Oh, Ki Won

    2013-01-01

    Recent studies suggest an association of vitamin D with obesity, diabetes and cardiovascular diseases. We analyzed the association of serum vitamin D level assessed by 25-hydroxyvitamin D3 {25(OH)D3 } with nonalcoholic fatty liver disease (NAFLD) in apparently healthy men. We performed a cross-sectional study of 6,567 Korean men who participated in a health screening program, evaluating the association of serum 25(OH)D3 levels with the risk of NAFLD assessed by abdominal ultrasonogram. Of the participants, 43.6% had NAFLD and 21.1% had metabolic syndrome. Age, serum calcium, and aspartate aminotransferase levels showed weak but significant positive correlations with 25(OH)D3 level; total cholesterol, triglycerides, low-density lipoprotein cholesterol and fasting insulin level showed weak but significant negative correlations with 25(OH)D3 level. The mean 25(OH)D3 level was significantly lower in participants with NAFLD than in those without (38.7 ± 9.0 vs. 39.7 ± 9.7 nmol/L, p < 0.001). When participants were divided into tertiles based on mean 25(OH)D3 level, the proportion with NAFLD significantly increased as mean 25(OH)D3 level decreased (40.0, 45.0 and 45.9%, p for linear trend < 0.001). Multiple logistic regression analyses with NAFLD as the dependent variable showed that the tertiles with lower 25(OH)D3 levels had a significantly increased risk for NAFLD compared with the highest tertile, even after adjusting for body mass index and metabolic syndrome (OR 1.247 and 1.408 vs. the highest tertile, p < 0.001). Thus, participants with higher serum 25(OH)D3 showed a significantly reduced risk for NAFLD compared with the low 25(OH)D3 groups, independent of obesity and metabolic syndrome.

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

    SciTech Connect

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

    1987-06-30

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

  19. [Correction by vitamin D3 of disturbed metabolism in patients with diabetes mellitus types 1 and 2].

    PubMed

    Komisarenko, Iu I

    2014-01-01

    Vitamin D deficiency is an increasingly recognized public health problem of population as a whole and against a background of different chronic diseases. The aim of the study was to determine the status of D-vitamin, mineral, carbohydrate and lipid metabolism in patients with diabetes 1 and 2 types and in the case of vitamin D3 application. The data on the impact of vitamin D3 deficiency on mineral, carbohydrate and lipid metabolism, as well as on pancreatic beta-cells functional activity in patients with diabetes mellitus types 1 and 2 are presented. Certain reasons that lead to the disruption of vitamin D3 metabolism in patients with diabetes mellitus and the results of vitamin D3 application in clinics are discussed.

  20. Cyclic changes of vitamin D and PTH are primarily regulated by solar radiation: 5-year analysis of a German (50 degrees N) population.

    PubMed

    Reusch, J; Ackermann, H; Badenhoop, K

    2009-05-01

    Cutaneous vitamin D precursor production depends on UV-exposure and is ineffective in most regions above latitudes of 50 degrees in winter. We hypothesized whether the cyclic course of vitamin D levels can be modelled with sunshine duration and would affect parathyroid hormone concentrations, but not calcium in a large patient population. We investigated 13330 blood samples from 6099 in- and out patients for 25(OH)D3, 1,25(OH)2D3, PTH, and total Ca in Frankfurt, Germany over 6.5 years. Vitamin D deficiency [25(OH)D3 <10 ng/ml] was found in 12.23% and vitamin D insufficiency [25(OH)D3 <20 ng/ml] in 40.62% of all the blood samples and more frequently during winter. We observed a significant difference between men and women, children and adults, migrants and local residents. Cycling of the curve was significantly related to Julian day for 25(OH)D3 and parathyroid hormone (PTH), but not for 1,25(OH)2D3 and Ca. The peak concentration of 25(OH)D3 was found at Aug 16th and correlated well with the length of day whereas PTH is inversely related with 25(OH)D (3). Seasonal cycling of 25(OH)D3-levels correlated significantly with Julian Day and inversely with PTH. This tight feed back ensures stable Ca concentrations within narrow limits. We conclude that changes in vitamin D levels are mainly regulated by solar radiation and to a lesser degree by other factors such as nutrition. PMID:19241329

  1. Protective effect of 1,25-dihydroxyvitamin D3 on ethanol-induced intestinal barrier injury both in vitro and in vivo.

    PubMed

    Chen, Shan-Wen; Ma, Yuan-Yuan; Zhu, Jing; Zuo, Shuai; Zhang, Jun-Ling; Chen, Zi-Yi; Chen, Guo-Wei; Wang, Xin; Pan, Yi-Sheng; Liu, Yu-Cun; Wang, Peng-Yuan

    2015-09-01

    Studies have suggested the role of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in protecting intestinal barrier function from injuries induced by multiple reagents. Vitamin D deficiency was reported to be associated with poor prognosis in patients with alcoholic liver disease (ALD). This study is designed to investigate the effect of 1,25(OH)2D3 on ethanol-induced intestinal barrier dysfunction and the underlying mechanisms utilizing Caco-2 cell monolayers and a mouse model with acute ethanol injury. In Caco-2 monolayers, ethanol significantly increased monolayer permeability, disrupted TJ distribution, increased phosphorylation level of MLC, and induced generation of ROS compared with controls. However, pre-treatment with 1,25(OH)2D3 greatly ameliorated the ethanol-induced barrier dysfunction, TJ disruption, phosphorylation level of MLC, and generation of ROS compared with ethanol-exposed monolayers. Mice fed with vitamin d-sufficient diet had a higher plasma level of 25(OH)D3 and were more resistant to ethanol-induced acute intestinal barrier injury compared with the vitamin d-deficient group. These results suggest that the suppression of generation of ROS and increased phosphorylation level of MLC might be one of the mechanisms underlying the protective effect of 1,25(OH)2D3 on ethanol-induced intestinal barrier injury and provide evidence for the application of vitamin D as therapeutic factors against ethanol-induced gut leakiness.

  2. 1,25-Dihydroxyvitamin D3 Suppresses Inflammation-Induced Expression of Plasminogen Activator Inhibitor-1 by Blocking Nuclear Factor-κB Activation

    PubMed Central

    Chen, Yunzi; Kong, Juan; Sun, Tao; Li, George; Szeto, Frances L.; Liu, Weicheng; Deb, Dilip K.; Wang, Youli; Zhao, Qun; Thadhani, Ravi; Li, Yan Chun

    2011-01-01

    Plasminogen activator inhibitor (PAI)-1 is a major fibrinolytic inhibitor. High PAI-1 is associated with increased renal and cardiovascular disease risk. Previous studies demonstrated PAI-1 down-regulation by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), but the molecular mechanism remains unknown. Here we show that exposure of mouse embryonic fibroblasts to TNFα or LPS led to a marked induction of PAI-1, which was blunted by 1,25(OH)2D3, NF-κB inhibitor or p65 siRNA, suggesting the involvement of NF-κB in 1,25(OH)2D3-induced repression. In mouse Pai-1 promoter a putative cis-κB element was identified at −299. EMSA and ChIP assays showed that TNF-α increased p65/p50 binding to this κB site, which was disrupted by 1,25(OH)2D3. Luciferase reporter assays showed that PAI-1 promoter activity was induced by TNFα or LPS, and the induction was blocked by 1,25(OH)2D3. Mutation of the κB site blunted TNFα, LPS or 1,25(OH)2D3 effects. 1,25(OH)2D3 blocked IκBα degradation and arrested p50/p65 nuclear translocation. In mice LPS stimulated PAI-1 expression in the heart and macrophages, and the stimulation was blunted by pre-treatment with a vitamin D analog. Together these data demonstrate that 1,25(OH)2D3 down-regulates PAI-1 by blocking NF-κB activation. Inhibition of PAI-1 production may contribute to the reno- and cardio-protective effects of vitamin D. PMID:21176770

  3. Regulation of calcitonin gene transcription by vitamin D metabolites in vivo in the rat.

    PubMed Central

    Naveh-Many, T; Silver, J

    1988-01-01

    Calcitonin is secreted by the C cells of the thyroid in response to a raised serum calcium, and acts on bone to lower serum calcium. The C cells have specific receptors for the dihydroxymetabolite of vitamin D3, 1,25(OH)2D3. Moreover, calcitonin stimulates the synthesis of 1,25(OH)2D3 in the kidney. Parathyroid hormone (PTH), the third calciotrophic hormone, is also trophic to the renal synthesis of 1,25(OH)2D3, and in turn 1,25(OH)2D3 inhibits PTH gene transcription and synthesis. We report here the marked inhibition of calcitonin gene transcription by the injection of physiologically relevant doses of 1,25(OH)2D3 to normal rats that did not raise serum calcium. Calcitonin mRNA levels after 100 pmol 1,25(OH)2D3 decreased to 6% of basal at 6 h and 4% at 48 h, and a dose response showed a marked effect even after 12.5 pmol 1,25(OH)2D3, with no appreciably greater effect with larger doses (up to 200 pmol). Control genes, actin, thyroglobulin (thyroid follicular cells), somatostatin (thyroid C-cells) were not affected by 1,25(OH)2D3. Gel blots showed that 1,25(OH)2D3 decreased calcitonin mRNA levels without any change in its size. In vitro nuclear transcription showed that 1,25(OH)2D3-treated (100 pmol) rats' calcitonin transcription was 10% of control, while thyroglobulin and actin were 100%. We propose that calcium is the major regulator of PTH and calcitonin secretion, while 1,25(OH)2D3 is an important regulator of PTH and calcitonin gene transcription. We believe this to be the first demonstration of an effect of 1,25(OH)2D3 on the C cells thereby establishing a new target organ and site of action of vitamin D. Calcitonin is trophic to 1,25(OH)2D3 synthesis, which in turn inhibits calcitonin synthesis, which are the components of a new endocrinological feedback loop. Images PMID:2891728

  4. A randomized study on the effect of Vitamin D3 supplementation on skeletal muscle morphology and Vitamin D receptor concentration in older women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies examining whether vitamin D supplementation increases muscle mass or muscle-specific vitamin D receptor (VDR) concentration are lacking. Our objective was to determine whether vitamin D3 4000 IU/d alters muscle fiber cross-sectional area (FCSA) and intramyonuclear VDR concentration over 4 mo...

  5. Determination of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in human serum using liquid chromatography with tandem mass spectrometry.

    PubMed

    Fang, Huiling; Yu, Songlin; Cheng, Qian; Cheng, Xinqi; Han, Jianhua; Qin, Xuzhen; Xia, Liangyu; Jiang, Xiaomei; Qiu, Ling

    2016-08-01

    Vitamin D plays important roles in skeletal metabolism and many other diseases, including chronic renal failure, hypoparathyroidism, sarcoidosis and rickets. 1α,25-dihydroxy vitamin D (1α,25(OH)2D), the active form of vitamin D, exhibits an extremely low serum concentration, which makes its quantification very challenging. High performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) is considered to be the "gold standard" for the determination of these chemicals, which are found in low concentrations in the serum, but conventionally, it needs tedious sample pretreatment procedures, such as solid phase extraction and derivatization. Herein, we describe a simple and rapid HPLC-MS/MS method for the simultaneous quantification of 1α,25-dihydroxy vitamin D3 (1α,25(OH)2D3) and 1α,25-dihydroxy vitamin D2 (1α,25(OH)2D2). The analytes were extracted from the matrix by liquid-liquid extraction, centrifuged to dryness and reconstituted with 75% methanol. Lithium acetate was employed to improve the ionization efficiency of 1α,25(OH)2D. The assay was sensitive with a low limit of quantitation of 10.0pg/mL for both 1α,25(OH)2D3 and 1α,25(OH)2D2 using a 0.5mL sample aliquot. Linearity was obtained over the range of 10.0pg/mL to 500pg/mL. Both the inter-assay and intra-assay precisions were <15%, and the analytical recoveries were within 100±5%. The performance evaluation of this assay demonstrated that it was a practical, sensitive and specific method for measuring the serum 1α,25(OH)2D3 and 1α,25(OH)2D2 concentrations. PMID:27240300

  6. Identification and regulation of 1,25-dihydroxyvitamin D3 receptor activity and biosynthesis of 1,25-dihydroxyvitamin D3. Studies in cultured bovine aortic endothelial cells and human dermal capillaries.

    PubMed Central

    Merke, J; Milde, P; Lewicka, S; Hügel, U; Klaus, G; Mangelsdorf, D J; Haussler, M R; Rauterberg, E W; Ritz, E

    1989-01-01

    Because 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been shown to play roles in both proliferation and differentiation of novel target cells, the potential expression of 1,25(OH)2D3 receptor (VDR) activity was investigated in cultured bovine aortic endothelial cells (BAEC). Receptor binding assays performed on nuclear extracts of BAEC revealed a single class of specific, high-affinity VDR that displayed a 4.5-fold increase in maximal ligand binding (Nmax) in rapidly proliferating BAEC compared with confluent, density-arrested cells. When confluent BAEC were incubated with activators of protein kinase C (PKC), Nmax increased 2.5-fold within 6-24 h and this upregulation was prevented by sphingosine, an inhibitor of PKC, as well as by actinomycin D or cycloheximide. Immunohistochemical visualization using a specific MAb disclosed nuclear localized VDR in venular and capillary endothelial cells of human skin biopsies, documenting the expression of VDR, in vivo, and validating the BAEC model. Finally, additional experiments indicated that BAEC formed the 1,25(OH)2D3 hormonal metabolite from 25(OH)D3 substrate, in vitro, and growth curves of BAEC maintained in the presence of 10(-8) M 1,25(OH)2D3 showed a 36% decrease in saturation density. These data provide evidence for the presence of a vitamin D microendocrine system in endothelial cells, consisting of the VDR and a 1 alpha-hydroxylase enzyme capable of producing 1,25(OH)2D3. That both components of this system are coordinately regulated, and that BAEC respond to the 1,25(OH)2D3 hormone by modulating growth kinetics, suggests the existence of a vitamin D autocrine loop in endothelium that may play a role in the development and/or functions of this pathophysiologically significant cell population. Images PMID:2542376

  7. Association of vitamin D3 with alveolar bone regeneration in dogs.

    PubMed

    Hong, Hsiang-Hsi; Yen, Tzung-Hai; Hong, Adrienne; Chou, Ting-An

    2015-06-01

    Designed sockets prepared on the mandibles of nine Beagle dogs were divided into three groups: Calcitriol +Alloplast, Alloplast and Empty. Five of the nine dogs received Vit.D3 and calcium supplement (Vit.D/Ca group), while the other four dogs without supplements were assigned to Non-Vit.D/Ca group. After 4 weeks, the extent of vertical ridge resorption (VRR), bone density (density), new bone formation (NBF) and implant stability quotient (ISQ) were measured. Following systemic Vit.D/Ca administration, the Empty subgroup showed significant differences from the Calcitriol + Alloplast subgroup on variants NBF/Density/VRR and the Alloplast subgroup on items NBF/Density/ISQ/VRR. Alternatively, the Calcitriol + Alloplast subgroup revealed higher values of NBF/Density/ISQ (P < 0.001) and a lower VRR value (P = 0.001) than the Alloplast subgroup. Although there were no significant differences in NBF (P = 0.349), density (P = 0.796), ISQ (P = 0.577) and VRR (0.979) comparisons on alloplast treatment between the Vit.D/Ca and Non-Vit.D/Ca groups, local application with Calcitriol + Alloplast demonstrated better NBF/Density/ISQ (P = 0.02 to <0.001) effects than which of Alloplast subgroups. Consequently, the results showed that both systemic and local vitamin D3 treatment might accelerate bone regeneration in dogs. Within the using dose, systemic vitamin D3 treatment displayed a superior stimulating effect than local vitamin D3 application did.

  8. Effects of vitamin D metabolites on healing of low phosphate, vitamin D-deficient induced rickets in rats.

    PubMed

    Atkin, I; Pita, J C; Ornoy, A; Agundez, A; Castiglione, G; Howell, D S

    1985-01-01

    A model of low-phosphate, vitamin D-deficient rachitic rats was used to compare the effects of 1 alpha(OH)D3, 1,25(OH)2D3, and 24,25(OH)2D3 on cartilage and bone. The rats were maintained for 3 weeks on a high-calcium, low-phosphate, vitamin D-deficient diet, during which period they developed severe rickets. The rachitic rats were injected for 2 or 3 consecutive days with a physiologic dose of either metabolite. Other littermates were given a single dose of 50,000 IU of cholecalciferol in combination with a normal diet. Samples of cartilage fluid (Cfl) and of blood were removed prior to sacrifice for biochemical studies of some parameters of calcification. These parameters were correlated with the results of light and electron microscopic studies of the growth plate cartilage and bone. Treatment with 1 alpha (OH)D3 or with 1,25(OH)2D3, in spite of increasing Ca and P levels in the Cfl, induced only partial healing of the rickets. In contrast, 24,25(OH)2D3 or vitamin D with a normal diet resulted in complete morphologic and biochemical healing of the rickets. Transmission electron microscopic (TEM) studies have shown partial mineralization of the wide hypertrophic zone of the growth plate following treatment with 1 alpha(OH)D3 or with 1,25(OH)2D3. Mineralization was more complete with 24,25(OH)2D3 treatment. The results of this study emphasize the importance of 24,25(OH)2D3 for normal endochondral bone formation and mineralization.

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

    PubMed

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

    2013-07-01

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

  10. Vitamin D and the skin: an ancient friend, revisited.

    PubMed

    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 introduced for the treatment of the hyperproliferative skin disease psoriasis. Recently, sebocytes were identified as 1,25(OH)(2)D(3)-responsive target cells, indicating that vitamin D analogues may be effective in the treatment of acne. Other new functions of vitamin D analogues include profound effects on the immune system as well as in various tissues protection against cancer and other diseases, including autoimmune and infectious diseases. It can be speculated that the investigation of biological effects of vitamin D analogues will lead to new therapeutic applications that, besides cancer prevention, may include the prevention and treatment of infectious as well as of inflammatory skin diseases. Additionally, it can be assumed that dermatological recommendations on sun protection and health campaigns for skin cancer prevention will have to be re-evaluated to guarantee a sufficient vitamin D status.

  11. Regulation of Dendritic Cell Function by Vitamin D

    PubMed Central

    Barragan, Myriam; Good, Misty; Kolls, Jay K.

    2015-01-01

    Studies over the last two decades have revealed profound immunomodulatory aspects of vitamin D on various aspects of the immune system. This review will provide an overview of Vitamin D metabolism, a description of dendritic cell subsets, and highlight recent advances on the effects of vitamin D on dendritic cell function, maturation, cytokine production and antigen presentation. The active form of vitamin D, 1,25(OH)2D3, has important immunoregulatory and anti-inflammatory effects. Specifically, the 1,25(OH)2D3-Vitamin D3 complex can affect the maturation and migration of many dendritic cell subsets, conferring a special immunoregulatory role as well as tolerogenic properties affecting cytokine and chemokine production. Furthermore, there have been many recent studies demonstrating the effects of Vitamin D on allergic disease and autoimmunity. A clear understanding of the effects of the various forms of Vitamin D will provide new opportunities to improve human health. PMID:26402698

  12. Dietary diallyl disulfide supplementation attenuates ethanol-mediated pulmonary vitamin D speciate depletion in C57Bl/6 mice

    PubMed Central

    McCaskill, Michael L.; Hottor, Henry T.; Sapkota, Muna; Wyatt, Todd A.

    2016-01-01

    Background Slightly more than 5 % of the United States population heavily consumes ethanol, i.e., more than 14 drinks for men and 7 drinks for women a week. Chronic ethanol consumption can result in increased liver disease, reduced recovery from burn injury, and more frequent and severe respiratory infections. Chronic ethanol over-consumption also leads to vitamin D dysmetabolism and depletion. Vitamin D is a fat-soluble pro-hormone that regulates musculoskeletal health, cellular proliferation/differentiation, and innate and adaptive immune response. Methods In this study, C57BL/6 mice were fed 20 % ethanol in their water ad libitum for 7 weeks. Some mice were fed either a standard chow or a modified diet containing 0.15 μg/day of diallyl disulfide (DADS). Whole blood, lung tissue, and bronchial alveolar lavage fluid (BALF) were collected at sacrifice and analyzed for 25(OH) D3, 1,25 (OH)2D3, vitamin D receptor VDR, CYP2E1, and CYP27B1 levels. Results Ethanol reduced 25(OH) D3 and 1,25 (OH)2D3 in lung tissue and BALF on average 31 %. The largest ethanol-mediated reduction was in the 1,25 (OH)2D3 (42 %) measured in the BALF. Dietary supplementation of DADS restored BALF and lung tissue protein of 25(OH) D3 and 1,25(OH)2D3 to control levels. Chronic ethanol consumption also resulted in tissue increases of vitamin D response (VDR) protein, Cyp2E1, and reductions in vitamin D-activating enzyme CYP27B1. All three of these effects were attenuated by dietary supplementation of DADS. Conclusions In conclusion, the pulmonary metabolic disturbances mediated by chronic ethanol consumption as measured by 1,25(OH)2D3 protein levels, epithelial lining fluid, and lung tissue can be ameliorated by dietary supplementation of DADS in C57BL/6 mice. PMID:27536382

  13. 19F NMR study on the complex of fluorinated vitamin D derivatives with vitamin D receptor: elucidation of the conformation of vitamin D ligands accommodated in the receptor.

    PubMed

    Morizono, Daisuke

    2011-12-28

    Nuclear receptors mediate allosteric communications where ligand binding initiates a cascade of signal transduction. The interaction of vitamin D with vitamin D receptor (VDR) was investigated by (19)F NMR spectroscopy of the complexes of three fluorinated vitamin D derivatives with the full-length rat VDR-LBD. In the (19)F NMR spectra of the VDR-ligand complexes, the A-ring of 4,4-difluoro-1,25(OH)2D3 was revealed to adopt β-conformation in the VDR in solution, and the spectra were shown to be dependent on the dissociation constant. While the complex of 4,4-difluoro-1,25(OH)2D3 with VDR exhibited a clear distinguishable (19)F NMR spectrum, those of (19)F-1,25(OH)2D3 stereoisomers, which have 10-fold higher VDR affinity than 4,4-difluoro-1,25(OH)2D3, did not. The solid-phase NMR technique was useful for (19)F-1,25(OH)2D3 stereoisomers. The fluorinated vitamin D derivatives showed marked changes in the chemical shift (Δ4-19.7 ppm) upon VDR-complex formation, and the ab initio MO method suggested that van der Waals interactions play a major role in the complex formation.

  14. The Current Recommended Vitamin D Intake Guideline for Diet and Supplements During Pregnancy Is Not Adequate to Achieve Vitamin D Sufficiency for Most Pregnant Women

    PubMed Central

    Field, Catherine J.; Kaplan, Bonnie J.; Rabi, Doreen M.; Maggiore, Jack A.; O’Beirne, Maeve; Hanley, David A.; Eliasziw, Misha; Dewey, Deborah; Weinberg, Amy; Ross, Sue J.

    2016-01-01

    Background The aims of this study were to determine if pregnant women consumed the recommended vitamin D through diet alone or through diet and supplements, and if they achieved the current reference range vitamin D status when their reported dietary intake met the current recommendations. Methods Data and banked blood samples collected in second trimester from a subset of 537 women in the APrON (Alberta Pregnant Outcomes and Nutrition) study cohort were examined. Frozen collected plasma were assayed using LC-MS/MS (liquid chromatography-tandem mass spectrometry) to determine 25(OH)D2, 25(OH)D3, 3-epi-25(OH)D3 concentrations. Dietary data were obtained from questionnaires including a Supplement Intake Questionnaire and a 24-hour recall of the previous day’s diet. Results Participants were 87% Caucasian; mean (SD) age of 31.3 (4.3); BMI 25.8 (4.7); 58% were primiparous; 90% had education beyond high school; 80% had a family income higher than CAN $70,000/year. 25(OH)D2, 25(OH)D3, and 3-epi-25(OH)D3) were identified in all of the 537 plasma samples;3-epi-25(OH)D3 contributed 5% of the total vitamin D. The median (IQR) total 25(OH)D (D2+D3) was 92.7 (30.4) nmol/L and 20% of women had 25(OH)D concentration < 75 nmol/L. The median (IQR) reported vitamin D intake from diet and supplements was 600 (472) IU/day. There was a significant relationship between maternal reported dietary vitamin D intake (diet and supplement) and 25(OH)D and 3-epi-25(OH)D3 concentrations in an adjusted linear regression model. Conclusions We demonstrated the current RDA (600 IU/ day) may not be adequate to achieve vitamin D status >75 nmol/L in some pregnant women who are residing in higher latitudes (Calgary, 51°N) in Alberta, Canada and the current vitamin D recommendations for Canadian pregnant women need to be re-evaluated. PMID:27367800

  15. Supranutritional oral supplementation with vitamin D3 and calcium and the effects on beef tenderness.

    PubMed

    Scanga, J A; Belk, K E; Tatum, J D; Smith, G C

    2001-04-01

    Ultimate meat tenderness can be influenced by numerous preslaughter and postmortem management techniques. Increased levels of intracellular Ca2+, through postmortem injection, infusion, or marination, have been shown to improve the tenderness of cooked meat products. Oral supplementation with vitamin D3 effectively increases serum Ca2+ and has been hypothesized to increase muscle Ca2+ content, the activity of muscle proteases, and thus the tenderness of cooked beef. Individual Charolais x Hereford heifers (n = 191) were assigned to an unsupplemented control group or groups that were supplemented via oral bolus (for dose regulation purposes) with one of seven levels of vitamin D3 (1, 2, 3, 4, or 5 x 10(6) IU D3/d, 2 x 10(6) IU DS/d plus 75 g CaCO3 or 4 x 106 IU D3/d plus 75 g CaCO3) for 2, 4, 6, or 8 d antemortem. Individual feedlot performance, serum Ca2+ levels, and carcass data were collected, and eight longissimus steaks/carcass were used to obtain Warner-Bratzler shear force values measured at 2, 7, 14, and 21 d postmortem for longissimus steaks cooked to 70 degrees or 85 degrees C. Cattle supplemented with 4 x 10(6) IU D3/d plus 75 g of CaCO3 had lower daily feed intake (as-fed) and reduced (P < 0.05) average daily gains compared with controls during the 8-d supplementation period. Additionally, supplemented cattle had numerically higher dressing percentages, possibly due to less fill at the time of slaughter, because carcass weights and USDA yield grades did not differ (P > 0.05) across treatment groups. Supplementation with 1, 2, 3, 4, or 5 x 10(6) IU D3/d, for 2 or more days, increased (P < 0.05) serum Ca2+ concentrations compared with controls. Whereas cattle that received additional dietary Ca2+ in the form of CaCO3 had the lowest blood serum Ca2+ concentration. Although blood serum Ca2+ was increased, supplementation with any level of vitamin D3 for any length of time up to 8 d did not improve (P > 0.05) Warner-Bratzler shear force at 2, 7, 14, or 21 d

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  17. 1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system

    PubMed Central

    Li, Yan Chun; Kong, Juan; Wei, Minjie; Chen, Zhou-Feng; Liu, Shu Q.; Cao, Li-Ping

    2002-01-01

    Inappropriate activation of the renin-angiotensin system, which plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis, may represent a major risk factor for hypertension, heart attack, and stroke. Mounting evidence from clinical studies has demonstrated an inverse relationship between circulating vitamin D levels and the blood pressure and/or plasma renin activity, but the mechanism is not understood. We show here that renin expression and plasma angiotensin II production were increased severalfold in vitamin D receptor–null (VDR-null) mice, leading to hypertension, cardiac hypertrophy, and increased water intake. However, the salt- and volume-sensing mechanisms that control renin synthesis are still intact in the mutant mice. In wild-type mice, inhibition of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] synthesis also led to an increase in renin expression, whereas 1,25(OH)2D3 injection led to renin suppression. We found that vitamin D regulation of renin expression was independent of calcium metabolism and that 1,25(OH)2D3 markedly suppressed renin transcription by a VDR-mediated mechanism in cell cultures. Hence, 1,25(OH)2D3 is a novel negative endocrine regulator of the renin-angiotensin system. Its apparent critical role in electrolytes, volume, and blood pressure homeostasis suggests that vitamin D analogues could help prevent or ameliorate hypertension. PMID:12122115

  18. Cholecalciferol (Vitamin D3) Improves Myelination and Recovery after Nerve Injury

    PubMed Central

    Chabas, Jean-Francois; Stephan, Delphine; Marqueste, Tanguy; Garcia, Stephane; Lavaut, Marie-Noelle; Nguyen, Catherine; Legre, Regis; Khrestchatisky, Michel

    2013-01-01

    Previously, we demonstrated i) that ergocalciferol (vitamin D2) increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii) that cholecalciferol (vitamin D3) improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i) to assess which form – ergocalciferol versus cholecalciferol – and which dose were the most efficient and ii) to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle), and compared to unlesioned rats (Control). Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day), cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i) the number of preserved or newly formed axons in the proximal end, ii) the mean axon diameter in the distal end, and iii) neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral nerve or

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

    PubMed

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

    2016-04-01

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

  20. Activation of the fructose 1,6-bisphosphatase gene by 1,25-dihydroxyvitamin D3 during monocytic differentiation.

    PubMed Central

    Solomon, D H; Raynal, M C; Tejwani, G A; Cayre, Y E

    1988-01-01

    Cells from the human leukemia cell line HL-60 undergo terminal monocyte-like differentiation after exposure to either the active circulating form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], or phorbol 12-myristate 13-acetate. Little is known about the genes that regulate monocytic differentiation. Using clonal variant cells of HL-60 origin, we constructed a cDNA library enriched for genes that are induced by 1,25-(OH)2D3. We now report that in HL-60, the fructose 1,6-bisphosphatase (FBPase; D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) gene is activated during 1,25-(OH)2D3-induced monocytic differentiation. This gene encodes two closely related mRNAs; one, activated by 1,25-(OH)2D3 at an early stage of HL-60 differentiation, encodes a protein that has homology to mammalian FBPase, a key enzyme in gluconeogenesis, although it does not exhibit its classical enzymatic activity. A second mRNA is activated by 1,25-(OH)2D3 mainly in peripheral blood monocytes. This mRNA is present in kidney as a unique transcript and encodes a protein with FBPase activity. Our data also show that this FBPase-encoding mRNA can be activated during monocytic maturation since it was detected in human alveolar macrophages. Images PMID:2842796

  1. Relationship of calcium absorption with 25(OH)D and calcium intake in children with rickets.

    PubMed

    Thacher, Tom D; Abrams, Steven A

    2010-11-01

    Nutritional rickets has long been considered a disease caused by vitamin D deficiency, but recent data indicate that inadequate dietary calcium intake is an important cause of rickets, particularly in tropical countries. Children with rickets due to calcium deficiency do not have very low 25(OH)D concentrations, and serum 1,25(OH)(2) D values are markedly elevated. Studies of Nigerian children with rickets demonstrated they have high fractional calcium absorption. A high-phytate diet was demonstrated to increase calcium absorption compared with the fasting state, and enzymatic dephytinization did not significantly improve calcium absorption. When given vitamin D, children with rickets have a marked increase in 1,25(OH)(2) D concentrations without any change in fractional calcium absorption. No positive relationship was found between fractional calcium absorption and serum 25(OH)D concentrations in children on low-calcium diets. More research is needed to understand the interaction between calcium and vitamin D and the role of vitamin D in calcium absorption.

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

    PubMed Central

    Pacini, Stefania; Morucci, Gabriele; Branca, Jacopo J. V.; Aterini, Stefano; Amato, Marcello; Gulisano, Massimo; Ruggiero, Marco

    2013-01-01

    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. PMID:23749205

  3. Synthesis of novel vitamin D3 analog with an additional ring annulated to A and seco-B rings.

    PubMed

    Sokolowska, Katarzyna; Sicinski, Rafal R

    2014-09-01

    A simple method for the synthesis of yet unknown 5E-vitamin D3 analogs with an additional six-membered ring connecting C-6 and C-19 was developed. Ring-closing metathesis (RCM) was used for efficient formation thereof from the corresponding 5E-isomers of 6-alkenyl vitamin D3 compounds which in turn were prepared from the 6-oxo-3,5-cyclovitamin D3. Reinvestigation of the Grignard reactions of this latter compound as well as the following acid-catalyzed cycloreversions showed discrepancies with the literature data describing the course of such processes.

  4. Synthesis of novel vitamin D3 analog with an additional ring annulated to A and seco-B rings.

    PubMed

    Sokolowska, Katarzyna; Sicinski, Rafal R

    2014-09-01

    A simple method for the synthesis of yet unknown 5E-vitamin D3 analogs with an additional six-membered ring connecting C-6 and C-19 was developed. Ring-closing metathesis (RCM) was used for efficient formation thereof from the corresponding 5E-isomers of 6-alkenyl vitamin D3 compounds which in turn were prepared from the 6-oxo-3,5-cyclovitamin D3. Reinvestigation of the Grignard reactions of this latter compound as well as the following acid-catalyzed cycloreversions showed discrepancies with the literature data describing the course of such processes. PMID:24928728

  5. Immune-modifying properties of topical vitamin D: Focus on dendritic cells and T cells.

    PubMed

    Gorman, Shelley; Judge, Melinda A; Hart, Prue H

    2010-07-01

    Topical creams containing the active form of vitamin D (1,25-dihydroxyvitamin D3; 1,25(OH)2D3) or analogues of this compound are currently used with some success to treat skin conditions including psoriasis and vitiligo. As well as targeting inflammatory processes in the skin, topical application of 1,25(OH)2D3 also affects the function of immune cells in the skin and draining lymph nodes. Topically applied 1,25(OH)2D3 reduces the number of dendritic cells in the skin, resulting in suppressed immunity and in particular reduced contact hypersensitivity (CHS) responses. Topical 1,25(OH)2D3 may also promote the migration of dendritic cells from the skin to the draining lymph nodes. Skin application of 1,25(OH)2D3 prevented the inflammatory effects of UVB irradiation on lymph node hypertrophy, when cell numbers were examined 4 days after skin treatment. In contrast, when 1,25(OH)2D3 was applied to UVB irradiated skin, there was no reversal in the suppression of CHS responses caused by UVB irradiation. Instead, 1,25(OH)2D3 had an additive effect with UVB to suppress CHS responses to a greater degree than UVB alone. In these studies, 1,25(OH)2D3 was applied to the treated skin of BALB/c mice immediately following UVB irradiation. Finally, topical 1,25(OH)2D3 also enhanced the number and suppressive activity of CD4+CD25+ regulatory T cells in the lymphatic tissue draining skin.

  6. 25(OH)D Status of Elite Athletes with Spinal Cord Injury Relative to Lifestyle Factors

    PubMed Central

    Pritchett, Kelly; Pritchett, Robert; Ogan, Dana; Bishop, Phil; Broad, Elizabeth; LaCroix, Melissa

    2016-01-01

    Background: Due to the potential negative impact of low Vitamin D status on performance-related factors and the higher risk of low Vitamin D status in Spinal Cord Injury (SCI) population, research is warranted to determine whether elite athletes with SCI have sufficient 25(OH)D levels. The purposes of this study were to examine: (1) the seasonal proportion of vitamin D insufficiency among elite athletes with SCI; and (2) to determine whether lifestyle factors, SCI lesion level, and muscle performance/function are related to vitamin D status in athletes with SCI. Methods: Thirty-nine members of the Canadian Wheelchair Sports Association, and the US Olympic Committee Paralympic program from outdoor and indoor sports were recruited for this study. Dietary and lifestyle factors, and serum 25(OH)D concentrations were assessed during the autumn (October) and winter (February/March). An independent t-test was used to assess differences in 25(OH)D status among seasons, and indoor and outdoor sports in the autumn and winter, respectively. Results: Mean ± SD serum 25(OH)D concentration was 69.6 ± 19.7 nmol/L (range from 30 to 107.3 nmol/L) and 67.4 ± 25.5 nmol/L (range from 20 to 117.3 nmol/L)in the autumn and winter, respectively. In the autumn, 15.4% of participants were considered vitamin D deficient (25(OH)D < 50 nmol/L) whereas 51.3% had 25(OH)D concentrations that would be considered insufficient (<80 nmol/L). In the winter, 15.4% were deficient while 41% of all participants were considered vitamin D insufficient. Conclusion: A substantial proportion of elite athletes with SCI have insufficient (41%–51%) and deficient (15.4%) 25(OH)D status in the autumn and winter. Furthermore, a seasonal decline in vitamin D status was not observed in the current study. PMID:27322316

  7. Calcium effects and systemic exposure of vitamin D3 analogues after topical treatment of active vitamin D3-containing ointments in rats.

    PubMed

    Hosomi, Atsushi; Hirabe, Maho; Tokuda, Takuya; Nakamura, Hiroaki; Amano, Toru; Okamoto, Tadao

    2016-10-01

    Topical agents containing vitamin D3 (VD3) analogues such as calcipotriol, maxacalcitol and tacalcitol and the combination of calcipotriol/betamethasone dipropionate (betamethasone) are prescribed for patients with psoriasis. However, they are known to occasionally cause hypercalcemia, and the frequency of hypercalcemia is suggested to vary according to the VD3 analogue used. In this study, to address the reason for these differences, the calcemic effects of maxacalcitol-, calcipotriol- and calcipotriol/betamethasone-containing ointments in rats were evaluated. The serum calcium levels in rats treated with ointments containing maxacalcitol, but not calcipotriol or calcipotriol/betamethasone, were significantly elevated, which is consistent with clinical observations. The serum concentration of VD3 analogue in rats treated with ointments containing calcipotriol and calcipotriol/betamethasone was lower than that in rats treated with maxacalcitol-containing ointment. Thus, the calcemic effects appear to be associated with the systemic exposure of VD3 analogues in rats. To understand the mechanism underlying the different systemic exposures of VD3 analogues, skin permeation and metabolic stability of VD3 analogues were evaluated. The cumulative amount of calcipotriol permeated through rat skin was significantly lower than that of maxacalcitol. On the other hand, the metabolic clearance of calcipotriol in rat hepatocytes was higher than that of maxacalcitol. Similar results were obtained using human skin and human hepatocytes. The current study demonstrates that the lower calcemic effects of calcipotriol- and calcipotriol/betamethasone-containing ointments are caused by the low systemic exposure of calcipotriol according to low skin permeability and rapid hepatic elimination after topical application.

  8. CD8+ T cells are not necessary for 1α,25-dihydroxyvitamin D3 to suppress experimental autoimmune encephalomyelitis in mice

    PubMed Central

    Meehan, Terrence F.; DeLuca, Hector F.

    2002-01-01

    In addition to its role in calcium and phosphorous homeostasis, 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3] appears to be a modulator of the immune system. Administration of 1,25-(OH)2D3 prevents disease in several autoimmune animal models, including experimental autoimmune encephalomyelitis (EAE). The vitamin D receptor is believed to mediate this activity. Among cells of the immune system, CD8+ T cells have the highest levels of the vitamin D receptor. Because CD8+ T cells have been implicated as both suppressors and effectors of the inflammation associated with multiple sclerosis and EAE, we examined the question of whether the 1,25-(OH)2D3 suppression of EAE occurs through a CD8+ T cell-dependent mechanism. To test this hypothesis, mice that are homozygous knockouts for the α chain of the CD8 receptor and have been characterized as lacking functional CD8+ T cells (CD8+ −/−) were provided 1,25-(OH)2D3 in their diet before EAE induction. Although CD8+ −/− mice fed the same diet lacking 1,25-(OH)2D3 have a high incidence of EAE, EAE did not occur in CD8+ −/− mice fed the diet containing 1,25-(OH)2D3. We conclude that CD8+ T cells neither are needed nor do they play a role in the prevention of EAE by 1,25-(OH)2D3. PMID:11929984

  9. Research resource: whole transcriptome RNA sequencing detects multiple 1α,25-dihydroxyvitamin D(3)-sensitive metabolic pathways in developing zebrafish.

    PubMed

    Craig, Theodore A; Zhang, Yuji; McNulty, Melissa S; Middha, Sumit; Ketha, Hemamalini; Singh, Ravinder J; Magis, Andrew T; Funk, Cory; Price, Nathan D; Ekker, Stephen C; Kumar, Rajiv

    2012-09-01

    The biological role of vitamin D receptors (VDR), which are abundantly expressed in developing zebrafish (Danio rerio) as early as 48 h after fertilization, and before the development of a mineralized skeleton and mature intestine and kidney, is unknown. We probed the role of VDR in developing zebrafish biology by examining changes in expression of RNA by whole transcriptome shotgun sequencing (RNA-seq) in fish treated with picomolar concentrations of the VDR ligand and hormonal form of vitamin D(3), 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2)D(3))].We observed significant changes in RNAs of transcription factors, leptin, peptide hormones, and RNAs encoding proteins of fatty acid, amino acid, xenobiotic metabolism, receptor-activator of NFκB ligand (RANKL), and calcitonin-like ligand receptor pathways. Early highly restricted, and subsequent massive changes in more than 10% of expressed cellular RNA were observed. At days post fertilization (dpf) 2 [24 h 1α,25(OH)(2)D(3)-treatment], only four RNAs were differentially expressed (hormone vs. vehicle). On dpf 4 (72 h treatment), 77 RNAs; on dpf 6 (120 h treatment) 1039 RNAs; and on dpf 7 (144 h treatment), 2407 RNAs were differentially expressed in response to 1α,25(OH)(2)D(3). Fewer RNAs (n = 481) were altered in dpf 7 larvae treated for 24 h with 1α,25(OH)(2)D(3) vs. those treated with hormone for 144 h. At dpf 7, in 1α,25(OH)(2)D(3)-treated larvae, pharyngeal cartilage was larger and mineralization was greater. Changes in expression of RNAs for transcription factors, peptide hormones, and RNAs encoding proteins integral to fatty acid, amino acid, leptin, calcitonin-like ligand receptor, RANKL, and xenobiotic metabolism pathways, demonstrate heretofore unrecognized mechanisms by which 1α,25(OH)(2)D(3) functions in vivo in developing eukaryotes.

  10. Quantifying the vitamin D3 synthesizing potential of UVB lamps at specific distances over time.

    PubMed

    Schmidt, Debra A; Mulkerin, Diane; Boehm, Daniel R; Ellersieck, Mark R; Lu, Zhiren; Campbell, Matthew; Chen, Tai C; Holick, Michael F

    2010-01-01

    The purpose of this study was to quantify the ultraviolet B (UVB) output and in vitro previtamin D(3) synthesis over time from various artificial light sources. Three incandescent lamps, T-Rex Active UVHeat 160 watt spot, T-Rex Active UVHeat 160 watt flood, and ZooMed PowerSun 160 watt flood, and two 1.2 m fluorescent lamps, Sylvania Blacklight 350 BL and ZooMed Reptisun 5.0, were studied. Total UVB irradiance and concentration of previtamin D synthesized using an in vitro ampoule model were quantified initially and at monthly intervals for 1 year. Incandescent lamps were measured at distances of 0.9 and 1.5 m while fluorescent lamps were measured at distances of 30.5 and 45.7 cm at the lamp's center, using both the radiometer and ampoules. Fluorescent lamp irradiance was also measured at the lamp's ends. Data were analyzed as a repeated measures split-plot in time using SAS with all mean differences determined using Least Squares Means. Incandescent lamp irradiance differences were seen at various distances. The UVHeat lamps had consistently higher previtamin D(3) production and irradiance readings compared with the PowerSun lamp. Reptisun 5.0 was consistently higher in UVB irradiance over Sylvania BL 350 at both 30.5 and 45.7 cm. However, there were no differences when comparing conversion of 7-dehydrocholesterol to previtamin D(3). Irradiance differences were detected between the centers and ends of the fluorescent lamps. Until UVB requirements for vitamin D(3) synthesis in animals are determined, it is impossible to state that one light is superior to another.

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

    PubMed

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

    2016-06-01

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

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

    PubMed

    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.

  13. [Is daily supplementation with vitamin D2 equivalent to daily supplementation with vitamin D3 in the elderly?].

    PubMed

    Seijo, Mariana; Mastaglia, Silvina; Brito, Graciela; Somoza, Julia; Oliveri, Beatriz

    2012-01-01

    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 (X ± 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 succeeded in achieving adequate levels of 25OHD (= 30 ng/ml).

  14. Exposure to UV Wavelengths in Sunlight Suppresses Immunity. To What Extent is UV-induced Vitamin D3 the Mediator Responsible?

    PubMed

    Hart, Prue H; Gorman, Shelley

    2013-02-01

    Reduced immunity following exposure of skin to UV radiation (UVR) may explain the positive latitude gradient measured for a number of autoimmune diseases (greater incidence of disease with residence at higher latitudes), including multiple sclerosis, allergic asthma and diabetes. Humans obtain >80% of their vitamin D3 by exposure of skin to UVR in sunlight. In experimental models, both vitamin D3-dependent and vitamin D3-independent pathways have been implicated in the mechanisms of UVR-induced systemic suppression of immunity. However, where does the balance of control lie? How important is vitamin D3 other than providing a biomarker of sun exposure? Are other molecules/pathways activated by UVR more important? Murine and human studies suggest many molecules may play a role and their participation may vary with different diseases and the time of UVR exposure or vitamin D3 sufficiency/deficiency. Although low vitamin D3 levels have been associated with increased prevalence and progression of human autoimmune diseases, the benefits of supplementation with vitamin D3 have not been definitive. Vitamin D3 levels are a measure of past sun exposure but vitamin D3-dependent and vitamin D3-independent immunosuppressive effects of UVR may play a role in control of autoimmune diseases.

  15. Exposure to UV Wavelengths in Sunlight Suppresses Immunity. To What Extent is UV-induced Vitamin D3 the Mediator Responsible?

    PubMed Central

    Hart, Prue H; Gorman, Shelley

    2013-01-01

    Reduced immunity following exposure of skin to UV radiation (UVR) may explain the positive latitude gradient measured for a number of autoimmune diseases (greater incidence of disease with residence at higher latitudes), including multiple sclerosis, allergic asthma and diabetes. Humans obtain >80% of their vitamin D3 by exposure of skin to UVR in sunlight. In experimental models, both vitamin D3-dependent and vitamin D3-independent pathways have been implicated in the mechanisms of UVR-induced systemic suppression of immunity. However, where does the balance of control lie? How important is vitamin D3 other than providing a biomarker of sun exposure? Are other molecules/pathways activated by UVR more important? Murine and human studies suggest many molecules may play a role and their participation may vary with different diseases and the time of UVR exposure or vitamin D3 sufficiency/deficiency. Although low vitamin D3 levels have been associated with increased prevalence and progression of human autoimmune diseases, the benefits of supplementation with vitamin D3 have not been definitive. Vitamin D3 levels are a measure of past sun exposure but vitamin D3-dependent and vitamin D3-independent immunosuppressive effects of UVR may play a role in control of autoimmune diseases. PMID:23592888

  16. TAZ regulates cell proliferation and sensitivity to vitamin D3 in intrahepatic cholangiocarcinoma.

    PubMed

    Xiao, Heng; Tong, Rongliang; Yang, Beng; Lv, Zhen; Du, Chengli; Peng, Chuanhui; Ding, Chaofeng; Cheng, Shaobing; Zhou, Lin; Xie, Haiyang; Wu, Jian; Zheng, Shusen

    2016-10-28

    The transcriptional coactivator with PDZ binding motif (TAZ) is reported as one of the nuclear effectors of Hippo-related pathways. TAZ is found overexpressed in many primary tumors and could regulate many biological processes. However, little is known about the role of TAZ in Intrahepatic Cholangiocarcinoma (ICC). In this study, we found that TAZ is expressed more in ICC tissues than in peritumoral tissue, and a robust expression of TAZ is correlated with a lower overall survival rate of ICC patients after hepatectomy. TAZ knockdown results in an increase in cell apoptosis, a promotion of cell-cycle arrest and a decrease in tumor size and weight in vivo through an increased expression of p53. Vitamin D3 can also inhibit cell proliferation by promoting p53 expression in ICC cells. A reduction in TAZ can also enhance the sensitivity of tumor cells to vitamin D by regulating the p53/CYP24A1 pathway. In conclusion, TAZ is associated with the proliferation and drug-resistance of ICC cells, and could be a novel therapeutic target for the treatment of ICC.

  17. The enhanced hypercalcemic response to 20-epi-1,25-dihydroxyvitamin D3 results from a selective and prolonged induction of intestinal calcium-regulating genes.

    PubMed

    Zella, Lee A; Meyer, Mark B; Nerenz, Robert D; Pike, J Wesley

    2009-08-01

    20-Epi-1,25-dihydroxyvitamin D(3) (20-epi-1,25(OH)(2)D(3)) is a vitamin D analog that exhibits unique biologic properties. The mechanism(s) responsible for these activities remains unclear. Here we explore the ability of 20-epi-1,25(OH)(2)D(3) to induce calcemic responses in mice in vivo and identify a potential mechanism. Surprisingly, the levels of calcemia induced at 24 h after single injections of equivalent doses of 1,25(OH)(2)D(3) or 20-epi-1,25(OH)(2)D(3) were similar, suggesting that both compounds were equal in both potency and efficacy. This similarity was also observed at genes involved in calcium homeostasis including, S100g (calbindin D9K), Trpv6, Cldn2 (claudin 2), Trpv5, and Tnfsf11 (Rankl) as well as Cyp24a1. Despite this, the activities of the two compounds at 48 h were strikingly different. Thus, whereas the activity of 1,25-dihydroxyvitamin D(3) declined at this time point, the response to 20-epi-1,25(OH)(2)D(3) was increased. This unique profile was not due to an exaggerated induction of calcium regulating genes in the intestine, kidney, or bone but to a sustained action on these genes in the intestine. This conclusion was supported by studies using in vivo chromatin immunoprecipitation analysis, which revealed a prolonged presence of vitamin D receptor and RNA polymerase II at the Trpv6 and Cyp24a1 promoters and a sustained increase in histone 4 acetylation in these gene regions as well. We conclude that 20-epi-1,25(OH)(2)D(3) displays superagonist properties largely as a result of its duration of action in the intestine. This action is likely due to a decrease in the rate of intestinal-specific degradation of the ligand rather than to an increase in the functional stability of the vitamin D receptor.

  18. The effect of a single, large bolus of vitamin D in healthy adults over the winter and following year: a randomized, double-blind, placebo-controlled trial

    PubMed Central

    Kearns, MD; Binongo, JNG; Watson, D; Alvarez, JA; Lodin, D; Ziegler, TR; Tangpricha, V

    2014-01-01

    BACKGROUND/OBJECTIVES Although single, high doses of vitamin D effectively maintain vitamin D sufficiency in several populations, no studies have evaluated healthy adults over winter, during which vitamin D status declines. This study investigated whether high-dose vitamin D3 given once to healthy adults before winter will (1) prevent the wintertime decline in vitamin D status, (2) promote vitamin D sufficiency 1 year following the dose and (3) prevent the rise of parathyroid hormone (PTH) concentrations. SUBJECTS/METHODS In this double-blind, placebo-controlled trial, we assessed plasma 25(OH)D and PTH concentrations at baseline, 5, 90 and 365 days after drug administration in 28 healthy adults. In all, >80% of subjects returned at each time point. RESULTS At baseline, the young, healthy participants had a mean plasma 25(OH)D concentration of 17.5 ± 6.1 ng/ml. Only two subjects exhibited plasma 25(OH)D concentrations >30 ng/ml. At 5 days, subjects randomized to vitamin D3 had a higher mean plasma 25(OH)D concentration compared with the placebo group (39.1 vs 19.1 ng/ml, P<0.001). Plasma 25(OH)D concentrations returned to baseline at 90 and 365 days in the vitamin D3 group and remained unchanged in the placebo group. PTH and calcium concentrations were unrelated to changes in 25(OH)D levels and similar between groups over time. CONCLUSIONS A dose of 250 000 IU of vitamin D3 given once in November resulted in a robust increase in plasma 25(OH)D after 5 days, but it was unable to sustain this increase after 90 days. A larger or more frequent dosing regimen may be needed for long-term vitamin D sufficiency. PMID:25271011

  19. Regulation of inflammation-primed activation of macrophages by two serum factors, vitamin D3-binding protein and albumin.

    PubMed Central

    Yamamoto, N; Kumashiro, R; Yamamoto, M; Willett, N P; Lindsay, D D

    1993-01-01

    A very small amount (0.0005 to 0.001%) of an ammonium sulfate [50% saturated (NH4)2SO4]-precipitable protein fraction of alpha 2-globulin efficiently supported inflammation-primed activation of macrophages. This fraction contains vitamin D3-binding protein essential for macrophage activation. Comparative macrophage activation studies with fetal calf serum, alpha 2-globulin fraction, 50% (NH4)2SO4 precipitate, and purified bovine vitamin D3-binding protein revealed that fetal calf serum and alpha 2-globulin fraction appear to contain an inhibitor for macrophage activation while ammonium sulfate precipitate contains no inhibitor. This inhibitor was found to be serum albumin. When bovine serum albumin (25 micrograms/ml) was added to a medium supplemented with 0.0005 to 0.05% (NH4)2SO4 precipitate or 1 to 10 ng of vitamin D3-binding protein per ml, activation of macrophages was inhibited. PMID:8225612

  20. 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.).

    PubMed

    Jäpelt, Rie Bak; Silvestro, Daniele; Smedsgaard, Jørn; Jensen, Poul Erik; Jakobsen, Jette

    2013-06-01

    Changes in vitamin D(3) 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 D(3) and 25-hydroxy vitamin D(3) were found in the leaves of all plants after UVB-treatment. S. glaucophyllum had the highest content, 200 ng vitamin D(3)/g dry weight and 31 ng 25-hydroxy vitamin D(3)/g dry weight, and was the only plant that also contained 1,25 dihydroxy vitamin D(3) in both free (32 ng/g dry weight) and glycosylated form (17 ng/g dry weight).

  1. 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.).

    PubMed

    Jäpelt, Rie Bak; Silvestro, Daniele; Smedsgaard, Jørn; Jensen, Poul Erik; Jakobsen, Jette

    2013-06-01

    Changes in vitamin D(3) 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 D(3) and 25-hydroxy vitamin D(3) were found in the leaves of all plants after UVB-treatment. S. glaucophyllum had the highest content, 200 ng vitamin D(3)/g dry weight and 31 ng 25-hydroxy vitamin D(3)/g dry weight, and was the only plant that also contained 1,25 dihydroxy vitamin D(3) in both free (32 ng/g dry weight) and glycosylated form (17 ng/g dry weight). PMID:23411232

  2. Effects of vitamin D supplementation during pregnancy on neonatal vitamin D and calcium concentrations: a systematic review and meta-analysis.

    PubMed

    Yang, Na; Wang, Linlin; Li, Zhixia; Chen, Sen; Li, Nan; Ye, Rongwei

    2015-07-01

    We conducted a meta-analysis to review the effects of vitamin D supplementation during pregnancy on neonatal 25-hydroxyvitamin D (25(OH)D) and calcium concentrations. Randomized controlled trials that supplemented subjects with vitamin D2 or D3 during pregnancy and reported cord blood 25(OH)D or calcium concentrations were included. A random-effect model was used to pool the data. Subgroup analyses were performed to explore the sources of heterogeneity. We searched PubMed, Web of Science, and Cochrane Library for relevant publications. Among 1768 publications identified by our search strategy, 13 studies met our inclusion criteria. Cord blood 25(OH)D concentration was significantly increased by maternal vitamin D supplementation (mean difference, 22.48 nmol/L; 95% confidence interval, 15.90-29.06 nmol/L) with high heterogeneity (I2 = 98.8%, P < .0001). No effects on cord blood calcium concentration was reported (mean difference, 0.05 mmol/L; 95% confidence interval, -0.04-0.13 mmol/L). Supplementation regimens and the different control groups may be the major sources of heterogeneity. Vitamin D supplementation during pregnancy can improve cord blood 25(OH)D concentration in women with low 25(OH)D concentration, but does not affect cord blood calcium concentration. Future researches are needed to evaluate the effect of maternal vitamin D supplementation in women with a normal 25(OH)D concentration and explore the combined effects of vitamin D, calcium, and multivitamins.

  3. Epigenome-wide effects of vitamin D and their impact on the transcriptome of human monocytes involve CTCF

    PubMed Central

    Seuter, Sabine; Neme, Antonio; Carlberg, Carsten

    2016-01-01

    The physiological functions of vitamin D are mediated by its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) activating the transcription factor vitamin D receptor (VDR). In THP-1 human monocytes we demonstrated epigenome-wide effects of 1,25(OH)2D3 at 8979 loci with significantly modulated chromatin accessibility. Maximal chromatin opening was observed after 24 h, while after 48 h most sites closed again. The chromatin-organizing protein CTCF bound to 14% of the 1,25(OH)2D3-sensitive chromatin regions. Interestingly, 1,25(OH)2D3 affected the chromatin association of CTCF providing an additional mechanism for the epigenome-wide effects of the VDR ligand. The 1,25(OH)2D3-modulated transcriptome of THP-1 cells comprised 1284 genes, 77.5% of which responded only 24 h after stimulation. During the 1,25(OH)2D3 stimulation time course the proportion of down-regulated genes increased from 0% to 44.9% and the top-ranking physiological function of the respective genes shifted from anti-microbial response to connective tissue disorders. The integration of epigenomic and transcriptomic data identified 165 physiologically important 1,25(OH)2D3 target genes, including HTT and NOD2, whose expression can be predicted primarily from epigenomic data of their genomic loci. Taken together, a large number of 1,25(OH)2D3-triggered epigenome-wide events precede and accompany the transcriptional activation of target genes of the nuclear hormone. PMID:26715761

  4. Mechanisms regulating osteoblast response to surface microtopography and vitamin D

    NASA Astrophysics Data System (ADS)

    Bell, Bryan Frederick, Jr.

    A comprehensive understanding of the interactions between orthopaedic and dental implant surfaces with the surrounding host tissue is essential in the design of advanced biomaterials that better promote bone growth and osseointegration of implants. Dental implants with roughened surfaces and high surface energy are well known to promote osteoblast differentiation in vitro and promote increased bone-to-implant contact in vivo. In addition, increased surface roughness increases osteoblasts response to the vitamin D metabolite 1alpha,25(OH)2D3. However, the exact mechanisms mediating cell response to surface properties and 1alpha,25(OH)2D3 are still being elucidated. The central aim of the thesis is to investigate whether integrin signaling in response to rough surface microtopography enhances osteoblast differentiation and responsiveness to 1alpha,25(OH)2D3. The hypothesis is that the integrin alpha5beta1 plays a role in osteoblast response to surface microtopography and that 1alpha,25(OH) 2D3 acts through VDR-independent pathways involving caveolae to synergistically enhance osteoblast response to surface roughness and 1alpha,25(OH) 2D3. To test this hypothesis the objectives of the studies performed in this thesis were: (1) to determine if alpha5beta 1 signaling is required for osteoblast response to surface microstructure; (2) to determine if increased responsiveness to 1alpha,25(OH)2D 3 requires the vitamin D receptor, (3) to determine if rough titanium surfaces functionalized with the peptides targeting integrins (RGD) and transmembrane proteoglycans (KRSR) will enhance both osteoblast proliferation and differentiation, and (4) to determine whether caveolae, which are associated with integrin and 1alpha,25(OH)2D3 signaling, are required for enhance osteogenic response to surface microstructure and 1alpha,25(OH)2D 3. The results demonstrate that integrins, VDR, and caveolae play important roles in mediating osteoblast response to surface properties and 1alpha,25

  5. 1,25-dihydroxyvitamin D3 and its nuclear receptor repress human α1(I) collagen expression and type I collagen formation

    PubMed Central

    Potter, James J.; Liu, Xiaopu; Koteish, Ayman; Mezey, Esteban

    2013-01-01

    Background Vitamin D deficiency is common in chronic liver disease particularly in those with severe liver fibrosis. Aims: To determine the effect of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on the human α1(I) collagen promoter and collagen formation by human stellate LX-2 cells and the mechanism of the effect of the vitamin D receptor (VDR) on the promoter. Methods Type I collagen was assessed by measurements of collagen mRNA and collagen protein and by transfection experiments. Binding of VDR to the α1(I) collagen promoter was determined by EMSA and ChIP assays. Results 1,25-(OH)2D3 decreased human α1(I) collagen mRNA and protein and the secretion of type I collagen by stellate cells after exposure to TGFβ1. Furthermore, 1,25-(OH)2D3 inhibited TGFβ1–induced activation of the α1(I) collagen promoter in transfected LX-2 cells. The effect of 1, 25-(OH)2D3 is mediated by the VDR, which binds at a proximal Sp1 site and also at a newly identified distal site on the collagen promoter. A VDR expression vector reduced the activities of the collagen promoter in transfected LX-2 cells. Conclusions 1,25-(OH)2D3 inhibits type I collagen formation in human stellate cells. The effect of 1,25-(OH)2D3 is mediated by its receptor which binds at a proximal Sp1.1 site and at a newly identified distal site on the collagen promoter. Correction of vitamin D deficiency in patients with chronic liver disease is a potential therapy to inhibit progression of fibrosis. PMID:23413886

  6. Effect of vitamin D3 in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats.

    PubMed

    George, Naijil; Kumar, T Peeyush; Antony, Sherin; Jayanarayanan, S; Paulose, C S

    2012-10-28

    Diabetes mellitus is a growing health problem worldwide and is associated with severe liver complications. The aim of the present study is to analyse the status of metabolic and free-radical-scavenging enzymes and second messengers in the liver of streptozotocin (STZ)-induced diabetic rats, and to determine the hepatoprotective role of vitamin D(3). All studies were performed using the liver of adult male Wistar rats. Gene expression studies were carried out using real-time PCR with specific probes. Second messenger levels were determined using (3)H-labelled Biotrak assay kits, and glucose uptake assay with D-[(14)C]glucose. The present results show that there was a decrease in hepatic glucose uptake, malate dehydrogenase activity, glycogen content, inositol triphosphate (IP(3)) and cyclic GMP levels, and superoxide dismutase, glutathione peroxidase, phospholipase C, cyclic AMP-responsive element-binding protein, vitamin D receptor (VDR) and insulin receptor (INSR) gene expression in the diabetic rats when compared with the controls (all P < 0·05), while cyclic AMP levels and GLUT2 expression were increased (P < 0·05). Treatment of the diabetic rats with vitamin D(3) and insulin reversed the altered parameters to near control values. In conclusion, the data suggest a novel role of vitamin D(3) in restoring impaired liver metabolism in STZ-induced diabetic rats by regulating glucose uptake, storage and metabolism. We demonstrated that the restoring effect of vitamin D(3) is mediated through VDR modulation, thereby improving signal transduction and controlling free radicals in the liver of diabetic rats. These data suggest a potential role for vitamin D(3) in the treatment of diabetes-associated hepatic complications.

  7. Nanoemulsion delivery systems for oil-soluble vitamins: Influence of carrier oil type on lipid digestion and vitamin D3 bioaccessibility.

    PubMed

    Ozturk, Bengu; Argin, Sanem; Ozilgen, Mustafa; McClements, David Julian

    2015-11-15

    The influence of carrier oil type on the bioaccessibility of vitamin D3 encapsulated within oil-in-water nanoemulsions prepared using a natural surfactant (quillaja saponin) was studied using a simulated gastrointestinal tract (GIT) model: mouth; stomach; small intestine. The rate of free fatty acid release during lipid digestion decreased in the following order: medium chain triglycerides (MCT) > corn oil ≈ fish oil > orange oil > mineral oil. Conversely, the measured bioaccessibility of vitamin D3 decreased in the following order: corn oil ≈ fish oil > orange oil > mineral oil > MCT. These results show that carrier oil type has a considerable impact on lipid digestion and vitamin bioaccessibility, which was attributed to differences in the release of bioactives from lipid droplets, and their solubilization in mixed micelles. Nanoemulsions prepared using long chain triglycerides (corn or fish oil) were most effective at increasing vitamin bioaccessibility. PMID:25977056

  8. Nanoemulsion delivery systems for oil-soluble vitamins: Influence of carrier oil type on lipid digestion and vitamin D3 bioaccessibility.

    PubMed

    Ozturk, Bengu; Argin, Sanem; Ozilgen, Mustafa; McClements, David Julian

    2015-11-15

    The influence of carrier oil type on the bioaccessibility of vitamin D3 encapsulated within oil-in-water nanoemulsions prepared using a natural surfactant (quillaja saponin) was studied using a simulated gastrointestinal tract (GIT) model: mouth; stomach; small intestine. The rate of free fatty acid release during lipid digestion decreased in the following order: medium chain triglycerides (MCT) > corn oil ≈ fish oil > orange oil > mineral oil. Conversely, the measured bioaccessibility of vitamin D3 decreased in the following order: corn oil ≈ fish oil > orange oil > mineral oil > MCT. These results show that carrier oil type has a considerable impact on lipid digestion and vitamin bioaccessibility, which was attributed to differences in the release of bioactives from lipid droplets, and their solubilization in mixed micelles. Nanoemulsions prepared using long chain triglycerides (corn or fish oil) were most effective at increasing vitamin bioaccessibility.

  9. Interleukin-1α mediates the antiproliferative effects of 1,25-dihydroxyvitamin D3 in prostate progenitor/stem cells.

    PubMed

    Maund, Sophia L; Barclay, Wendy W; Hover, Laura D; Axanova, Linara S; Sui, Guangchao; Hipp, Jason D; Fleet, James C; Thorburn, Andrew; Cramer, Scott D

    2011-08-01

    Vitamin D(3) is a promising preventative and therapeutic agent for prostate cancer, but its implementation is hampered by a lack of understanding about its mechanism of action. Upon treatment with 1α,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3), vitamin D(3)], the metabolically active form of vitamin D(3), adult prostate progenitor/stem cells (PrP/SC) undergo cell-cycle arrest, senescence, and differentiation to an androgen receptor-positive luminal epithelial cell fate. Microarray analyses of control- and vitamin D(3)-treated PrP/SCs revealed global gene expression signatures consistent with induction of differentiation. Interestingly, one of the most highly upregulated genes by vitamin D(3) was the proinflammatory cytokine interleukin-1α (IL-1α). Systems biology analyses supported a central role for IL-1α in the vitamin D(3) response in PrP/SCs. siRNA-mediated knockdown of IL-1α abrogated vitamin D(3)-induced growth suppression, establishing a requirement for IL-1α in the antiproliferative effects of vitamin D(3) in PrP/SCs. These studies establish a system to study the molecular profile of PrP/SC differentiation, proliferation, and senescence, and they point to an important new role for IL-1α in vitamin D(3) signaling in PrP/SCs.

  10. Genetic Ancestry, Skin Reflectance and Pigmentation Genotypes in Association with Serum Vitamin D Metabolite Balance

    PubMed Central

    Wilson, Robin Taylor; Roff, Alanna N.; Dai, P. Jenny; Fortugno, Tracey; Douds, Jonathan; Chen, Gang; Grove, Gary L.; Nikiforova, Sheila Ongeri; Barnholtz-Sloan, Jill; Frudakis, Tony; Chinchilli, Vernon M.; Hartman, Terryl J.; Demers, Laurence M.; Shriver, Mark D.; Canfield, Victor A.; Cheng, Keith C.

    2012-01-01

    Background Lower serum vitamin D (25(OH)D) among individuals with African ancestry is attributed primarily to skin pigmentation. However, the influence of genetic polymorphisms controlling for skin melanin content has not been investigated. Therefore, we investigated differences in non-summer serum vitamin D metabolites according to self-reported race, genetic ancestry, skin reflectance and key pigmentation genes (SLC45A2 and SLC24A5). Materials and Methods Healthy individuals reporting at least half African American or half European American heritage were frequency matched to one another on age (+/− 2 years) and sex. 176 autosomal ancestry informative markers were used to estimate genetic ancestry. Melanin index was measured by reflectance spectrometry. Serum vitamin D metabolites (25(OH)D3, 25(OH)D2 and 24,25(OH)2D3) were determined by high performance liquid chromatography (HPLC) tandem mass spectrometry. Percent 24,25(OH)2D3 was calculated as a percent of the parent metabolite (25(OH)D3). Stepwise and backward selection regression models were used to identify leading covariates. Results Fifty African Americans and 50 European Americans participated in the study. Compared with SLC24A5 111Thr homozygotes, individuals with the SLC24A5 111Thr/Ala and 111Ala/Ala genotypes had respectively lower levels of 25(OH)D3 (23.0 and 23.8 nmol/L lower, p-dominant=0.007), and percent 24,25(OH)2D3 (4.1 and 5.2 percent lower, p-dominant=0.003), controlling for tanning bed use, vitamin D/fish oil supplement intake, race/ethnicity, and genetic ancestry. Results were similar with melanin index adjustment, and were not confounded by glucocorticoid, oral contraceptive, or statin use. Conclusions The SLC24A5 111Ala allele was associated with lower serum vitamin 25(OH)D3 and lower percent 24,25(OH)2D3, independently from melanin index and West African genetic ancestry. PMID:23525585

  11. Stimulation by 1,25-dihydroxyvitamin D3 of in vitro mineralization induced by osteoblast-like MC3T3-E1 cells

    SciTech Connect

    Matsumoto, T.; Igarashi, C.; Takeuchi, Y.; Harada, S.; Kikuchi, T.; Yamato, H.; Ogata, E. )

    1991-01-01

    Although vitamin D is essential for mineralization of bone, it is as yet unclear whether vitamin D has a direct stimulatory effect on the bone mineralization process. In the present study, the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on in vitro mineralization mediated by osteoblast-like MC3T3-E1 cells was examined. MC3T3-E1 cells continued to grow after they reached confluency, and DNA content and alkaline phosphatase activity increased linearly until about 16 days of culture, whereas 45Ca accumulation into cell and matrix layer remained low. After this period, DNA content plateaued, and 45Ca accumulation increased sharply. Histological examination by von Kossa staining revealed that calcium was accumulated into extracellular matrix. In addition, needle-shaped mineral crystals similar to hydroxyapatite crystals could be demonstrated in between collagen fibrils by electron microscopy. Thus, MC3T3-E1 cells differentiate in vitro into cells with osteoblastic phenotype and exhibit mineralization. When MC3T3-E1 cells were treated with 1,25(OH)2D3 at this stage of culture, there was a dose-dependent stimulation of 45Ca accumulation by 1,25(OH)2D3, and a significant stimulation of 45Ca accumulation was observed with 3 x 10(-10) M 1,25(OH)2D3. Although 1,25(OH)2D3 enhanced alkaline phosphatase activity and collagen synthesis at the early phase of culture, it did not affect any of these parameters at the late phase when 1,25(OH)2D3 stimulated mineralization. Neither 24,25-dihydroxyvitamin D3 nor human PTH(1-34) affected mineralization in the presence or absence of 1,25(OH)2D3. These results demonstrate that 1,25(OH)2D3 stimulates matrix mineralization induced by osteoblastic MC3T3-E1 cells, and are consistent with the possibility that 1,25(OH)2D3 has a direct stimulatory effect on bone mineralization process.

  12. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis(e–Pub ahead of print)(LOE Classification)

    PubMed Central

    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.

    2010-01-01

    Objective: 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. Methods: 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. Results: 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 413nmol/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. Conclusions: High-dose vitamin D (∼10,000 IU/day) in multiple sclerosis is safe, with evidence of immunomodulatory effects. Classification of evidence: 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

  13. [Simultaneous determination of vitamins A, D3 and E in infant formula and adult nutritions by online two-dimensional liquid chromatography].

    PubMed

    Zhang, Yanhai; Qibule, Hasi; Jin, Yan; Wang, Jia; Ma, Wenli

    2015-03-01

    A rapid method for the simultaneous determination of vitamins A, D3 and E in infant formula and adult nutritions has been developed using online two-dimensional liquid chromatography (2D-LC). First of all, C8 and polar embedded C18 columns were chosen as the first and second dimensional column respectively according to hydrophobic-subtraction model, which constituted excellent orthogonal separation system. The detection wavelengths were set at 263 nm for vitamin D3, 296 nm for vitamin E and 325 nm for vitamin A. The purification of vitamin D3 and quantifications of vitamins A and E were completed simultaneously in the first dimensional separation using the left pump of Dual Gradient LC (DGLC) with methanol, acetonitrile and water as mobile phases. The heart-cutting time window of vitamin D3 was confirmed according to the retention time of vitamin D3 in the first dimensional separation. The elute from the first dimensional column (1-D column) which contained vitamin D3 was collected by a 500 µL sample loop and then taken into the second dimensional column (2-D column) by the right pump of DGLC with methanol, acetonitrile and water as mobile phases. The quantification of vitamin D3 was performed in the second dimensional separation with vitamin D2 as internal standard. At last, this method was applied for the analysis of the three vitamins in milk powder, cheese and yogurt. The injected sample solution with no further purification was pre-treated by hot-saponification using 1. 25 kg/L KOH solution and extracted by petroleum ether solvent. The recoveries of vitamin D3 spiked in all samples were 75.50%-85.00%. There was no statistically significant difference for the results between this method and standard method through t-test. The results indicate that vitamins A, D3 and E in infant formula and adult fortified dairy can be determined rapidly and accurately with this method.

  14. Dietary Vitamin D and Its Metabolites Non-Genomically Stabilize the Endothelium.

    PubMed

    Gibson, Christopher C; Davis, Chadwick T; Zhu, Weiquan; Bowman-Kirigin, Jay A; Walker, Ashley E; Tai, Zhengfu; Thomas, Kirk R; Donato, Anthony J; Lesniewski, Lisa A; Li, Dean Y

    2015-01-01

    Vitamin D is a known modulator of inflammation. Native dietary vitamin D3 is thought to be bio-inactive, and beneficial vitamin D3 effects are thought to be largely mediated by the metabolite 1,25(OH)2D3. Reduced serum levels of the most commonly measured precursor metabolite, 25(OH)D3, is linked to an increased risk of multiple inflammatory diseases, including: cardiovascular disease, arthritis, multiple sclerosis, and sepsis. Common to all of these diseases is the disruption of endothelial stability and an enhancement of vascular leak. We previously performed an unbiased chemical suppressor screen on a genetic model of vascular instability, and identified cholecalciferol (D3, dietary Vitamin D3) as a factor that had profound and immediate stabilizing and therapeutic effects in that model. In this manuscript we show that the presumed inactive sterol, D3, is actually a potent and general mediator of endothelial stability at physiologically relevant concentrations. We further demonstrate that this phenomenon is apparent in vitamin D3 metabolites 25(OH)D3 and 1,25(OH)2D3, and that the effects are independent of the canonical transcription-mediated vitamin D pathway. Our data suggests the presence of an alternative signaling modality by which D3 acts directly on endothelial cells to prevent vascular leak. The finding that D3 and its metabolites modulate endothelial stability may help explain the clinical correlations between low serum vitamin D levels and the many human diseases with well-described vascular dysfunction phenotypes. PMID:26469335

  15. Deglycosylation of serum vitamin D3-binding protein leads to immunosuppression in cancer patients.

    PubMed

    Yamamoto, N; Naraparaju, V R; Asbell, S O

    1996-06-15

    Serum vitamin D3-binding protein (Gc protein) can be converted by beta-galactosidase of B cells and sialidase of T cells to a potent macrophage activating factor, a protein with N-acetylgalactosamine as the remaining sugar moiety. Thus, Gc protein is the precursor of the macrophage activating factor (MAF). Treatment of Gc protein with immobilized beta-galactosidase and sialidase generates an extremely high titered MAF, Gc-MAF. When peripheral blood monocytes/macrophages of 52 patients bearing various types of cancer were incubated with 100 pg/ml of GcMAF, the monocytes/macrophages of all patients were efficiently activated. However, the MAF precursor activity of patient plasma Gc protein was found to be severely reduced in about 25% of this patient population. About 45% of the patients had moderately reduced MAF precursor activities. Loss of the precursor activity was found to be due to deglycosylation of plasma Gc protein by alpha-N-acetylgalactosaminidase detected in the patient's bloodstream. The source of the enzyme appeared to be cancerous cells. Radiation therapy decreased plasma alpha-N-acetylgalactosaminidase activity with concomitant increase of precursor activity. This implies that radiation therapy decreases the number of cancerous cells capable of secreting alpha-N-acetylgalactosaminidase. Both alpha-N-acetylgalactosaminidase activity and MAF precursor activity of Gc protein in patient bloodstream can serve as diagnostic and prognostic indices. PMID:8665521

  16. Structural modification of serum vitamin D3-binding protein and immunosuppression in AIDS patients.

    PubMed

    Yamamoto, N; Naraparaju, V R; Srinivasula, S M

    1995-11-01

    A serum glycoprotein, vitamin D3-binding protein (Gc protein), can be converted by beta-galactosidase of stimulated B lymphocytes and sialidase of T lymphocytes to a potent macrophage-activating factor (MAF), a protein with N-acetylgalactosamine as the remaining sugar moiety. Thus, Gc protein is a precursor for MAF. Treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generates an extremely high-titered MAF (GcMAF). When peripheral blood monocytes/macrophages of 46 HIV-infected patients were treated with GcMAF (100 pg/ml), the monocytes/macrophages of all patients were efficiently activated. However, the MAF precursor activity of plasma Gc protein was low in 16 (35%) of of these patients. Loss of the MAF precursor activity appeared to be due to deglycosylation of plasma Gc protein by alpha-N-acetylgalactosaminidase found in the patient blood stream. Levels of plasma alpha-N-acetylgalactosaminidase activity in individual patients had an inverse correlation with the MAF precursor activity of their plasma Gc protein. Thus, precursor activity of Gc protein and alpha-N-acetylgalactosaminidase activity in patient blood can serve as diagnostic and prognostic indices. PMID:8573395

  17. Combining Aspirin with Cholecalciferol (Vitamin D3) – A Potential New Tool for Controlling Possum Populations

    PubMed Central

    Morgan, David R.; Arrow, Jane; Smith, Mark P.

    2013-01-01

    The introduced Australian brushtail possum is a major vertebrate pest in New Zealand, with impacts on conservation and agriculture being managed largely through poisoning operations. Cholecalciferol (vitamin D3) is registered for use in controlling possums and despite its many advantages it is expensive and relatively inhumane. Combination of a high proportion of aspirin with a low proportion of cholecalciferol was effective in killing high proportions of groups of acclimatised, caged possums: this is attributed to both an unexpectedly high toxicity of the type of cholecalciferol used, and a proposed synergistic mechanism between the two compounds. Death was caused by localised damage to heart ventricles by aspirin, and inhibition of tissue repair by both aspirin and cholecalciferol. The observed toxicosis had lower impact on the welfare of possums than either compound administered alone, particularly aspirin alone. Residue analyses of bait remains in the GI tract suggested a low risk of secondary poisoning by either compound. The combination of cholecalciferol and aspirin has the potential to meet key requirements of cost-effectiveness and humaneness in controlling possum populations, but the effect of the combination in non-target species has yet to be tested. PMID:23950982

  18. The role of vitamin D3 upregulated protein 1 in thioacetamide-induced mouse hepatotoxicity

    SciTech Connect

    Kwon, Hyo-Jung; Lim, Jong-Hwan; Han, Jong-Tak; Lee, Sae-Bhom; Yoon, Won-Kee; Nam, Ki-Hoan; Choi, In-Pyo; Kim, Dae-Yong; Won, Young-Suk; Kim, Hyoung-Chin

    2010-11-01

    Thioacetamide (TA) is a commonly used drug that can trigger acute hepatic failure (AHF) through generation of oxidative stress. Vitamin D3 upregulated protein 1 (VDUP1) is an endogenous inhibitor of thioredoxin, a ubiquitous thiol oxidoreductase, that regulates cellular redox status. In this study, we investigated the role of VDUP1 in AHF using a TA-induced liver injury model. VDUP1 knockout (KO) and wild-type (WT) mice were subjected to a single intraperitoneal TA injection, and various parameters of hepatic injury were assessed. VDUP1 KO mice displayed a significantly higher survival rate, lower serum alanine aminotransferase and aspartate aminotransferase levels, and less hepatic damage, compared to WT mice. In addition, induction of apoptosis was decreased in VDUP1 KO mice, with the alteration of caspase-3 and -9 activities, Bax-to-Bcl-2 expression ratios, and mitogen activated protein kinase (MAPK) signaling pathway. Importantly, analysis of TA bioactivation revealed lower plasma clearance of TA and covalent binding of [{sup 14}C]TA to liver macromolecules in VDUP1 KO mice. Furthermore, the level of oxidative stress was significantly less in VDUP1 KO mice than in their WT counterparts, as evident from lipid peroxidation assay. These results collectively indicate that VDUP1 deficiency protects against TA-induced acute liver injury via lower bioactivation of TA and antioxidant effects.

  19. Comparison of biologically effective spectra for erythema and pre-vitamin D3 synthesis

    NASA Astrophysics Data System (ADS)

    Parisi, A. V.; Turnbull, D. J.; Turner, J.

    2009-01-01

    The short wavelength cut-off (λc), the wavelength of the maximum spectral UV (λMax) of spectral pre-vitamin D3 effective solar UV irradiance (UVD3), and the spectral erythemal UV (UVEry) were compared at 5-min intervals over a 6-month period at solar zenith angles (SZA) ranging from 4.7° to 80°. Averaged over the entire period, λc for UVD3 is higher by 1.05 nm than that for UVEry. The λMax is higher for UVD3 compared to UVEry for SZA < ~50°. For higher SZA (>55°), the ratio of λMax for UVD3 to that for UVEry is less than 1. As the erythemal action spectrum extends into the UVA, the ratio of UVD3 to UVEry irradiances decreases with increasing SZA, along with a decrease in the ratio of λMax for UVD3 compared to UVEry. The changes in λc and λMax influence both personal UVD3 and UVEry exposure and, to take this into account, a dual calibration technique for polysulphone dosimeters has been developed to simultaneously provide measurements of both types of exposure.

  20. Vitamin D3 May Ameliorate the Ketoconazole Induced Adrenal Injury: Histological and Immunohistochemical Studies on Albino Rats

    PubMed Central

    Khalil, Mahmoud Salah

    2015-01-01

    Ketoconazole (KZ) is used widely for treating the superficial, systemic fungal activities and hyperandrogenemic states. Its uses are limited by its deleterious effect on histological structure and function of the adrenal cortex. This study investigates whether vitamin D3 supplement can ameliorate the morphological changes induced by KZ. Thirty four adult male albino rats were randomized into control group (Group I) which was subdivided into: control 1 (n=7) and control 2 (n=7): In control 1, rats were intraperitoneal (I.P) injected once with 1 ml of polyethylene glycol-400 for 15 consecutive days and control 2 rats were injected I.P with (1 μg/kg) of vitamin D3 for the same period. Group II (n=10): rats were I.P injected with KZ (10 mg/100 g of body weight) once daily for 15 days; Group III (n=10): rats were I.P concomitantly injected with KZ and vitamin D3 similar doses to animals in groups II and control 2 respectively. Blood samples were collected to determine plasma ACTH, corticosterone and aldosterone levels. The right adrenal specimens sections were stained with Haematoxylin & Eosin and Masson Trichrome for histological studies and treated with Bax, Ubiquitin and vitamin D receptors for immunohistochemical studies. KZ induced adrenal cortical morphological changes in forms of disturbed adrenocorticocyte cytological architecture, nuclear changes, and intracellular lipid accumulation. KZ also increased adrenal Bax and Ub but decreased the vitamin D receptors immunopositive staining expression, in addition to increased plasma ACTH as well as decreased corticosterone and aldosterone levels. These changes were ameliorated by supplementing with vitamin D3. PMID:26379312

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

    PubMed Central

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

    1974-01-01

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

  2. Optimal vitamin D status and serum parathyroid hormone concentrations in African American women123

    PubMed Central

    Aloia, John F; Talwar, Sonia A; Pollack, Simcha; Feuerman, Martin; Yeh, James K

    2009-01-01

    Background Optimal vitamin D status for the prevention of osteoporosis has been inferred from examinations of the serum 25-hydroxyvitamin D [25(OH)D] concentration below which there is an increase in serum parathyroid hormone (PTH). Objective The objectives of the study were to ascertain whether a threshold for serum 25(OH)D exists below which serum PTH increases and whether persons with 25(OH)D above this threshold have lower rates of bone loss than do persons with 25(OH)D below the threshold. Design The relation of serum 25(OH)D to serum PTH was analyzed in 208 African American women studied longitudinally for 3 y. These healthy women in midlife were randomly assigned to receive placebo or 800 IU vitamin D3/d; after 2 y, the vitamin D3 supplementation was increased to 2000 IU/d. Both groups received calcium supplements to ensure an adequate calcium intake. A systematic literature review found a wide range of threshold values in part due to varied calcium intake. Results A Loess plot suggested a breakpoint between 40 and 50 nmol/L for serum 25(OH)D. A line-line model was fitted to the data, and it showed a spline knot at 44 nmol/L. A heuristic approach verified that PTH does not decline as rapidly when the serum concentration of 25(OH)D is >40 nmol/L as when it is <40 nmol/L. We found no significant difference in rates of bone loss between persons with 25(OH)D concentrations above and below 40 nmol/L. Conclusion Although a threshold for 25(OH)D can be identified, we suggest that it should not be used to recommend optimal vitamin D status. PMID:16960175

  3. Vitamin D and Mortality.

    PubMed

    Pilz, Stefan; Grübler, Martin; Gaksch, Martin; Schwetz, Verena; Trummer, Christian; Hartaigh, Bríain Ó; Verheyen, Nicolas; Tomaschitz, Andreas; März, Winfried

    2016-03-01

    In this narrative review, we aim to summarize and discuss the current evidence linking vitamin D and mortality. Low 25-hydroxyvitamin D [25(OH)D] concentrations are associated with an increased risk of mortality. This has been shown in different cohort studies including general populations, as well as various patient cohorts. Some single-study results and meta-analyses indicate that the shape of the relationship between 25(OH)D and mortality follows a U- or a reverse J-shaped curve. Interassay and laboratory differences are, however, a limitation of most previous surveys, and standardization of 25(OH)D measurements is needed for future investigations. Apart from observational data, it has been documented in meta-analyses of randomized controlled trials that vitamin D3 supplementation is associated with a moderate, yet statistically significant, reduction in mortality. This latter finding must be interpreted in light of some limitations such as incomplete follow-up data, but such a reduction of mortality with vitamin D3 supplementation as the finding of meta-analyses of randomized controlled trials strongly argues for the benefits and, importantly, also the safety of vitamin D. PMID:26977039

  4. Serum 25(OH)D seasonality in urologic patients from central Italy.

    PubMed

    Calgani, Alessia; Iarlori, Marco; Rizi, Vincenzo; Pace, Gianna; Bologna, Mauro; Vicentini, Carlo; Angelucci, Adriano

    2016-09-01

    Hypovitaminosis D is increasingly recognized as a cofactor in several diseases. In addition to bone homeostasis, vitamin D status influences immune system, muscle activity and cell differentiation in different tissues. Vitamin D is produced in the skin upon exposure to UVB rays, and sufficient levels of serum 25(OH)D are dependent mostly on adequate sun exposure, and then on specific physiologic variables, including skin type, age and Body Mass Index (BMI). In contrast with common belief, epidemiologic data are demonstrating that hypovitaminosis D must be a clinical concern not only in northern Countries. In our study, we investigated vitamin D status in a male population enrolled in a urology clinic of central Italy. In addition, we evaluated the correlation between vitamin D status and UVB irradiance measured in our region. The two principal pathologies in the 95 enrolled patients (mean age 66years) were benign prostate hypertrophy and prostate carcinoma. >50% of patients had serum 25(OH)D values in the deficient range (<20ng/mL), and only 16% of cases had serum vitamin D concentration higher than 30ng/mL (optimal range). The seasonal stratification of vitamin D concentrations revealed an evident trend with the minimum mean value recorded in April and a maximum mean value obtained in September. UVB irradiance measured by pyranometer in our region (Abruzzo, central Italy) revealed a large difference during the year, with winter months characterized by an UV irradiance about tenfold lower than summer months. Then we applied a mathematical model in order to evaluate the expected vitamin D production according to the standard erythemal dose measured in the different seasons. In winter months, the low available UVB radiation and the small exposed skin area resulted not sufficient to obtain the recommended serum doses of vitamin D. Although in summer months UVB irradiance was largely in excess to produce vitamin D in the skin, serum vitamin D resulted sufficient in

  5. Inter-relationship of vitamins A, D and K in incidence of renal calcification in A/J mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Matrix gamma-carboxyglutamic acid protein (MGP), a vitamin K-dependent protein, is involved in regulation of tissue calcification. In mice, 9-cis retinoic acid (9-cis RA) mitigates 1alpha, 25 dihydroxyvitamin D3 [1,25(OH)2D3]-induced renal calcification. It is not known if the mechanism(s) underlyin...

  6. A pilot randomized, controlled trial of vitamin D repletion to determine if endothelial function improves in patients with systemic lupus erythematosus

    PubMed Central

    Kamen, Diane L; Oates, Jim

    2015-01-01

    The endothelium is important not only in regulating vascular tone but also in modulating inflammation. Patients with systemic lupus erythematosus (SLE) have deficits in these endothelial functions. Vitamin D is a nuclear hormone that regulates vascular endothelial nitric oxide synthase activity and expression. Many SLE patients have insufficient levels of vitamin D. The effect of this hormone on vascular endothelial function in SLE patients is not known. This study was designed to determine the effect size of repleting vitamin D levels on endothelial function in patients with SLE and vitamin D deficiency. SLE patients with 25(OH) vitamin D (25(OH)D) levels < 20 ng/ml were randomized to oral vitamin D3 (D3) doses that did or did not raise 25(OH)D levels to ≥ 32 ng/ml. Endothelial function was measured with flow-mediated dilation (FMD) before and after 16 weeks of vitamin D3 supplementation. Half of those who achieved 25(OH)D levels of ≥32 ng/ml experienced increases in FMD, while none of those with continued low 25(OH)D levels did. Those with increases in FMD had significantly higher final 25(OH)D levels. Using the effect size from this study, future studies designed to test the effect of repleting 25(OH)D on FMD in vitamin D deficient SLE patients will require 35 patients in each group. These results suggest a potential role for vitamin D in SLE-related endothelial dysfunction and that an adaptive multi-arm treat-to-target serum level trial design may increase the efficiency and likelihood of success of such a study. PMID:26351776

  7. Acute fluid shifts influence the assessment of serum vitamin D status in critically ill patients

    PubMed Central

    2010-01-01

    Introduction Recent reports have highlighted the prevalence of vitamin D deficiency and suggested an association with excess mortality in critically ill patients. Serum vitamin D concentrations in these studies were measured following resuscitation. It is unclear whether aggressive fluid resuscitation independently influences serum vitamin D. Methods Nineteen patients undergoing cardiopulmonary bypass were studied. Serum 25(OH)D3, 1α,25(OH)2D3, parathyroid hormone, C-reactive protein (CRP), and ionised calcium were measured at five defined timepoints: T1 - baseline, T2 - 5 minutes after onset of cardiopulmonary bypass (CPB) (time of maximal fluid effect), T3 - on return to the intensive care unit, T4 - 24 hrs after surgery and T5 - 5 days after surgery. Linear mixed models were used to compare measures at T2-T5 with baseline measures. Results Acute fluid loading resulted in a 35% reduction in 25(OH)D3 (59 ± 16 to 38 ± 14 nmol/L, P < 0.0001) and a 45% reduction in 1α,25(OH)2D3 (99 ± 40 to 54 ± 22 pmol/L P < 0.0001) and i(Ca) (P < 0.01), with elevation in parathyroid hormone (P < 0.0001). Serum 25(OH)D3 returned to baseline only at T5 while 1α,25(OH)2D3 demonstrated an overshoot above baseline at T5 (P < 0.0001). There was a delayed rise in CRP at T4 and T5; this was not associated with a reduction in vitamin D levels at these time points. Conclusions Hemodilution significantly lowers serum 25(OH)D3 and 1α,25(OH)2D3, which may take up to 24 hours to resolve. Moreover, delayed overshoot of 1α,25(OH)2D3 needs consideration. We urge caution in interpreting serum vitamin D in critically ill patients in the context of major resuscitation, and would advocate repeating the measurement once the effects of the resuscitation have abated. PMID:21110839

  8. Vitamin D and UV exposure in chronic kidney disease

    PubMed Central

    Krause, Rolfdieter

    2013-01-01

    With loss of renal function and decreasing glomerula filtration rate the serum levels of 25-hydroxyvitamin D [25(OH)D] as well as 1,25-dihydroxyvitamin D [1,25 (OH)2 D] often decrease simultaneously. In representative groups of German patients on renal replacement therapy (hemodialysis, peritoneal dialysis, kidney transplantation) our group retrospectively analyzed the vitamin D status over a period of 12 y (1995‒2006). Only 11% of patients had a serum level of 25(OH)D that was > 30 ng/ml, more than 70% had a level of 25(OH)D < 20 ng/ml. In clinical trials we used sun-simulating artificial lamps to produce vitamin D3 in the skin. Partial-body irradiation (15% of body surface) was used during the routine hemodialysis treatment. Whole-body UV exposure was done in a standing position three times a week before the hemodialysis treatment. With both procedures we observed an increase of the serum level of 25(OH)2D3 by approx. 35–50% over a period of 2‒3 mo, maintenance of trabecular bone mineral density and a normalization of systolic and diastolic blood pressure. Heart rate variability improved during the whole-body radiation intervention period by 20‒25%. Patients who continued the whole-body irradiation regularly two or three times before starting the routine hemodialysis session had maintained normal levels of circulating 25(OH)D3 and of 1,25(OH)2D3. Therefore, from our data it can be recommended that intermittent suberythemal UVB exposure with a sun-simulation spectrum is effective to treat and/or protect against vitamin D deficiency in chronic and end-stage kidney disease patients. PMID:24494043

  9. The effect of place of residence and lifestyle on vitamin D deficiency in pregnancy: Comparison of eastern and western parts of Turkey

    PubMed Central

    Gür, Esra Bahar; Turan, Gülüzar Arzu; Tatar, Sümeyra; Gökduman, Ayşe; Karadeniz, Muammer; Çelik, Gülnaz; Genç, Mine; Güçlü, Serkan

    2014-01-01

    Objective The aim of this study was to determine the prevalence and the predictive factors of vitamin D deficiency in pregnancy and the compliance with “The National Vitamin D Support Program” at Turkey’s easternmost and westernmost provinces. Material and Methods Lifestyles of women at 24–28 weeks of pregnancy were assessed using a questionnaire form, and serum 25-hydroxyvitamin D3 (25(OH)D3) levels were measured. Results Vitamin D deficiency (≤20 ng/mL) in pregnant women had a prevalence of 27.8% in İzmir and 76.3% in Erzurum. The compliance of “The National Vitamin D Support Program” was 8% in İzmir and 32.6% in Erzurum. Clothing style, fish consumption, seaside holiday duration, and 1200 IU/day vitamin D replacement had an effect on 25(OH)D3 levels in pregnant subjects in İzmir, whereas only holiday duration and 1200 IU/day vitamin D replacement affected 25(OH)D3 levels in Erzurum. However, when a threshold for 25(OH)D3 level was considered ≥32 ng/mL, lifestyles did not affect 25(OH)D3 level. Conclusion The effect of lifestyle on 25(OH)D3 level in pregnancy is limited, especially in cold regions. We recommended increasing the compliance with “The National Vitamin D Support Program” at the follow-up of all pregnant women, irrespective of region and season. PMID:25317042

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

    PubMed

    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.

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

    PubMed

    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. PMID:27356607

  12. Vitamin D3 inhibits lipopolysaccharide-induced placental inflammation through reinforcing interaction between vitamin D receptor and nuclear factor kappa B p65 subunit.

    PubMed

    Chen, Yuan-Hua; Yu, Zhen; Fu, Lin; Wang, Hua; Chen, Xue; Zhang, Cheng; Lv, Zheng-Mei; Xu, De-Xiang

    2015-06-12

    It is increasingly recognized that vitamin D3 (VitD3) has an anti-inflammatory activity. The present study investigated the effects of maternal VitD3 supplementation during pregnancy on LPS-induced placental inflammation and fetal intrauterine growth restriction (IUGR). All pregnant mice except controls were intraperitoneally injected with LPS (100 μg/kg) daily from gestational day (GD)15-17. In VitD3 + LPS group, pregnant mice were orally administered with VitD3 (25 μg/kg) before LPS injection. As expected, maternal LPS exposure caused placental inflammation and fetal IUGR. Interestingly, pretreatment with VitD3 repressed placental inflammation and protected against LPS-induced fetal IUGR. Further analysis showed that pretreatment with VitD3, which activated placental vitamin D receptor (VDR) signaling, specifically suppressed LPS-induced activation of nuclear factor kappa B (NF-κB) and significantly blocked nuclear translocation of NF-κB p65 subunit in trophoblast gaint cells of the labyrinth layer. Conversely, LPS, which activated placental NF-κB signaling, suppressed placental VDR activation and its target gene expression. Moreover, VitD3 reinforced physical interaction between placental VDR and NF-κB p65 subunit. The further study demonstrates that VitD3 inhibits placental NF-κB signaling in VDR-dependent manner. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity. Overall, the present study provides evidence for roles of VDR as a key regulator of placental inflammation.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-06-09

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  17. Protective Effect of Topical Vitamin D3 against Photocarcinogenesis in a Murine Model

    PubMed Central

    Kim, Ji Seok; Jung, Minyoung; Yoo, Jiyeon; Choi, Eung Ho; Park, Byung Cheol; Kim, Myung Hwa

    2016-01-01

    Background Although the incidence of non-melanoma skin cancer is increasing, there are no effective practical preventive measures other than avoiding sun exposure. Objective To elucidate the protective effect of topical application of biologically active vitamin D3 (calcitriol) on skin cancer development caused by exposure to ultraviolet (UV). Methods Groups of hairless mice were topically treated with either calcitriol or vehicle immediately after exposure to UVB and UVA three times weekly for the initial 20 weeks, and without UV exposure in the following 6 weeks. Tumor number was counted and biopsies were done for histopathologic analysis. The changes of cyclobutane pyrimidine dimer (CPD) were evaluated 1 hour and 11 hours after short term of UV exposure and application of calcitriol. For safety evaluation, blood test and body weights were evaluated at 23rd and 25th week. Results Total tumor count and number of tumors less than 3 mm in size tended to be fewer in calcitriol group, and tumors more than 3 mm in size showed significantly lower tumor formation rate in calcitriol group. Single application of calcitriol reduced CPD at 1 hour and 11 hours after UV exposure. Histopathologic analysis showed tumors with lower grade malignancy in calcitriol group which suggested a delay in tumor progression. However, serum levels of calcium and phosphate in calcitriol group were above normal range, and weight loss was found. Conclusion Topical calcitriol may suppress the formation and progression of UV-induced non-melanoma skin cancer by enhancing the repair mechanism of UV damage. PMID:27274628

  18. Early indicators of survival following exposure to mustard gas: Protective role of 25(OH)D.

    PubMed

    Das, Lopa M; Binko, Amy M; Traylor, Zachary P; Duesler, Lori R; Dynda, Scott M; Debanne, Sara; Lu, Kurt Q

    2016-04-25

    The use of sulfur mustard (SM) as a chemical weapon for warfare has once again assumed center stage, endangering civilian and the military safety. SM causes rapid local skin vesication and late-onset systemic toxicity. Most studies on SM rely on obtaining tissue and blood for characterizing burn pathogenesis and assessment of systemic pathology, respectively. However the present study focuses on developing a non-invasive method to predict mortality from high dose skin SM exposure. We demonstrate that exposure to SM leads to a dose dependent increase in wound area size on the dorsal surface of mice that is accompanied by a progressive loss in body weight loss, blood cytopenia, bone marrow destruction, and death. Thus our model utilizes local skin destruction and systemic outcome measures as variables to predict mortality in a novel skin-based model of tissue injury. Based on our recent work using vitamin D (25(OH)D) as an intervention to treat toxicity from SM-related compounds, we explored the use of 25(OH)D in mitigating the toxic effects of SM. Here we show that 25(OH)D offers protection against SM and is the first known demonstration of an intervention that prevents SM-induced mortality. Furthermore, 25(OH)D represents a safe, novel, and readily translatable potential countermeasure following mass toxic exposure. PMID:26940683

  19. Quantifying UV exposure, vitamin D status and their relationship in a group of high school students in an alpine environment.

    PubMed

    Gröbner, Matthias; Gröbner, Julian; Hülsen, Gregor

    2015-02-01

    The relationship between personal UV exposure and vitamin D status was studied among 7 high school students from Davos, Switzerland from March to August 2013. The personal UV exposure was monitored using electronic dosimeters, while blood samples were taken at monthly intervals to determine the serum concentration of 25-hydroxyvitamin D3 (25(OH)D3). During school days students were exposed to 1.7% of the ambient UV irradiance, while 85% of the cumulative UV dose was obtained on weekends and holidays. Insufficient vitamin D levels in March (9 ng ml(-1) 25(OH)D3) rose to 25(OH)D3 concentrations of over 40 ng ml(-1), meeting sufficient levels in August. The increase in vitamin D levels among 5 high school students correlated well (r = 0.89) with their measured personal UV exposure, yielding a mean increase in serum 25(OH)D3 concentration of 0.38 ± 0.22 ng ml(-1) per 100 J m(-2) of vitamin D-weighted UV exposure, a value consistent with other studies. During certain periods of the study, increases in vitamin D status and UV doses differed from the average of the whole study, implying that other factors must influence vitamin D metabolism.

  20. Vitamin D status predicts reproductive fitness in a wild sheep population

    PubMed Central

    Handel, Ian; Watt, Kathryn A.; Pilkington, Jill G.; Pemberton, Josephine M.; Macrae, Alastair; Scott, Philip; McNeilly, Tom N.; Berry, Jacqueline L.; Clements, Dylan N.; Nussey, Daniel H.; Mellanby, Richard J.

    2016-01-01

    Vitamin D deficiency has been associated with the development of many human diseases, and with poor reproductive performance in laboratory rodents. We currently have no idea how natural selection directly acts on variation in vitamin D metabolism due to a total lack of studies in wild animals. Here, we measured serum 25 hydroxyvitamin D (25(OH)D) concentrations in female Soay sheep that were part of a long-term field study on St Kilda. We found that total 25(OH)D was strongly influenced by age, and that light coloured sheep had higher 25(OH)D3 (but not 25(OH)D2) concentrations than dark sheep. The coat colour polymorphism in Soay sheep is controlled by a single locus, suggesting vitamin D status is heritable in this population. We also observed a very strong relationship between total 25(OH)D concentrations in summer and a ewe’s fecundity the following spring. This resulted in a positive association between total 25(OH)D and the number of lambs produced that survived their first year of life, an important component of female reproductive fitness. Our study provides the first insight into naturally-occurring variation in vitamin D metabolites, and offers the first evidence that vitamin D status is both heritable and under natural selection in the wild. PMID:26757805

  1. Vitamin D receptor expression in human bone tissue and dose-dependent activation in resorbing osteoclasts

    PubMed Central

    Zarei, Allahdad; Morovat, Alireza; Javaid, Kassim; Brown, Cameron P

    2016-01-01

    The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor (VDR), we examined their response to different concentrations of 25-hydroxy vitamin D3 [25(OH)D3] (100 or 500 nmol·L−1) and 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] (0.1 or 0.5 nmol·L−1) metabolites in cell cultures. Specifically, CD14+ monocytes were cultured in charcoal-stripped serum in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Tartrate-resistant acid phosphatase (TRAP) histochemical staining assays and dentine resorption analysis were used to identify the size and number of osteoclast cells, number of nuclei per cell and resorption activity. The expression of VDR was detected in human bone tissue (ex vivo) by immunohistochemistry and in vitro cell cultures by western blotting. Quantitative reverse transcription-PCR (qRT-PCR) was used to determine the level of expression of vitamin D-related genes in response to vitamin D metabolites. VDR-related genes during osteoclastogenesis, shown by qRT-PCR, was stimulated in response to 500 nmol·L−1 of 25(OH)D3 and 0.1–0.5 nmol·L−1 of 1,25(OH)2D3, upregulating cytochrome P450 family 27 subfamily B member 1 (CYP27B1) and cytochrome P450 family 24 subfamily A member 1 (CYP24A1). Osteoclast fusion transcripts transmembrane 7 subfamily member 4 (tm7sf4) and nuclear factor of activated T-cell cytoplasmic 1 (nfatc1) where downregulated in response to vitamin D metabolites. Osteoclast number and resorption activity were also increased. Both 25(OH)D3 and 1,25(OH)2D3 reduced osteoclast size and number when co-treated with RANKL and M-CSF. The evidence for VDR expression in resorbing osteoclasts in vivo and low-dose effects of 1,25(OH)2D3 on osteoclasts in vitro

  2. Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption123

    PubMed Central

    Land, Benjamin B.; Wickham, Robert J.; Maldonado-Aviles, Jaime; de Araujo, Ivan E.; Addy, Nii A.

    2016-01-01

    Abstract 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. PMID:27257625

  3. Vitamin D inhibits development of liver fibrosis in an animal model but cannot ameliorate established cirrhosis.

    PubMed

    Abramovitch, Shirley; Sharvit, Efrat; Weisman, Yosef; Bentov, Amir; Brazowski, Eli; Cohen, Gili; Volovelsky, Oded; Reif, Shimon

    2015-01-15

    1,25(OH)2D3, the active form of vitamin D, has an antiproliferative and antifibrotic effect on hepatic stellate cells. Our aim was to investigate the potential of 1,25(OH)2D3 to inhibit the development of liver fibrosis and to ameliorate established fibrosis in vivo. The antifibrotic effect of 1,25(OH)2D3 was investigated in a thioacetamide (TAA) model (as a preventive treatment and as a remedial treatment) and in a bile duct ligation model. In the preventive model, rats received simultaneously intraperitoneum injection of TAA and/or 1,25(OH)2D3 for 10 wk. In the remedial model, rats were treated with TAA for 10 wk and then received 1,25(OH)2D3 or saline for 8 wk. Fibrotic score was determined by Masson staining. Collagen I, α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase-1 (TIMP1), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) expression were measured by Western blot analysis and real-time PCR. Hypercalemia was detected by chemistry measurements. Preventive treatment of 1,25(OH)2D3 significantly suppressed liver fibrosis both macroscopically and microscopically and significantly lowered the fibrotic score of the TAA + 1,25(OH)2D3 group compared with the TAA group. 1,25(OH)2D3 significantly inhibited expression of PDGF and TGF-β by ∼50% and suppressed the expression of collagen Iα1, TIMP1, and α-SMA by approximately three-, two-, and threefold, respectively. In contrast, 1,25(OH)2D3 was inefficient in amelioration of established liver fibrosis. Administration of 1,25(OH)2D3 to bile duct ligation rats led to a high mortality rate probably caused by hypercalcemia. We conclude that 1,25(OH)2D3 may be considered as a potential preventive treatment in an in vivo model but failed to ameliorate established cirrhosis.

  4. A lentiviral vector-based genetic sensor system for comparative analysis of permeability and activity of vitamin D3 analogues in xenotransplanted human skin.

    PubMed

    Staunstrup, Nicklas Heine; Bak, Rasmus O; Cai, Yujia; Svensson, Lars; Petersen, Thomas K; Rosada, Cecilia; Stenderup, Karin; Bolund, Lars; Mikkelsen, Jacob Giehm

    2013-03-01

    Vitamin D3 analogues are widely used topical and oral remedies for various ailments such as psoriasis, osteoporosis and secondary hyperparathyroidism. In topical treatment, high skin permeability and cellular uptake are key criteria for beneficial effects due to the natural barrier properties of skin. In this study, we wish to establish an in vivo model that allows the comparison of permeability and activity of vitamin D3 analogues in human skin. We generate a bipartite, genetic sensor technology that combines efficient lentivirus-directed gene delivery to xenotransplanted human skin with vitamin D3-induced expression of a luciferase reporter gene and live imaging of animals by bioluminescence imaging. Based on the induction of a transcriptional activator consisting of the vitamin D receptor fused to the Gal4 DNA-binding domain, the vitamin D3-responsive sensor facilitates non-invasive and rapid assessment of permeability and functional properties of vitamin D3 analogues. By topical application of a panel of vitamin D3 analogues onto 'sensorized' human skin, the sensor produces a drug-induced readout with a magnitude and persistence that allow a direct comparative analysis of different analogues. This novel genetic tool has great potential as a non-invasive in vivo screening system for further development and refinement of vitamin D3 analogues.

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

    PubMed

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

    2015-04-01

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

  6. [Vitamin D-dependent type-1 rickets: diagnosis and treatment of a further case].

    PubMed

    Pela, I; Bini, R; Seracini, D

    1996-01-01

    We describe a child with vitamin D dependent rickets type 1, who developed clinical signs of the disease at three months of age. The principal manifestations were hypocalcemia and seizure with EEG abnormalities. The circulating level of 1 alpha, 25 (OH)2D3 was low despite a normal level of 25 (OH)D3 and an adequate vitamin D supplementation. The patient responded to calcium gluconate infusions and pharmacologic doses of 1 alpha, 25 (OH)2D3 and a normalization of calcemia was obtained. After six months the therapy was progressively reduced to physiological dosage with optimal metabolic control. The patient is now 2.5 years old and receive a maintenance dose of calcitriol of 0.125 mcg/day. His clinical, biochemical and radiologic features are normal. PMID:8767587

  7. Comparable vitamin D3 metabolism in the endometrium of patients with recurrent spontaneous abortion and fertile controls.

    PubMed

    Tavakoli, Maryam; Salek-Moghaddam, Alireza; Jeddi-Tehrani, Mahmood; Talebi, Saeed; Kazemi-Sefat, Golnaz-Ensieh; Vafaei, Sedigheh; Mohammadzadeh, Afsaneh; Sheikhhassani, Shahrzad; Zarnani, Amir-Hassan

    2015-05-01

    Vitamin D exerts important roles during pregnancy, and its deficiency may be associated with several pregnancy complications, including pregnancy loss, yet no data are available for molecules involved in vitamin D metabolism in patients with unexplained recurrent spontaneous abortion. In this study, we investigated possible difference in endometrial expression of vitamin D3 receptor (VDR), 1α-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1) in women with recurrent spontaneous abortion (n = 8) and healthy controls (n = 8). Gene expression of VDR, CYP27B1, and CYP24A1 was determined by real-time PCR, while VDR and CYP27B1 proteins were localized by immunohistochemistry and their abundance was validated by Western blot. We found that both patient and control groups expressed comparable levels of endometrial VDR, CYP27B1, and CYP24A1 transcripts. In line with the gene-expression results, CYP27B1 and different isoforms of VDR protein were present at the same abundance in the endometria of both groups. No significant alteration in VDR and CYP27B1 immunoreactivity pattern was found in the endometrium of patients compared to fertile controls, however. The results of the present study, therefore, do not support the hypothesis of differential expression of key molecules involved in vitamin D3 metabolism in the endometrium of recurrent spontaneous abortion patients and fertile controls.

  8. A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy.

    PubMed

    Owens, Daniel J; Sharples, Adam P; Polydorou, Ioanna; Alwan, Nura; Donovan, Timothy; Tang, Jonathan; Fraser, William D; Cooper, Robert G; Morton, James P; Stewart, Claire; Close, Graeme L

    2015-12-15

    Skeletal muscle is a direct target for vitamin D. Observational studies suggest that low 25[OH]D correlates with functional recovery of skeletal muscle following eccentric contractions in humans and crush injury in rats. However, a definitive association is yet to be