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Vitamin D3 AND hypercalcemia

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https://www.readbyqxmd.com/read/28913556/high-dose-vitamin-d3-supplementation-decreases-the-number-of-colonic-cd103-dendritic-cells-in-healthy-subjects
#1
Nina Friis Bak, M Bendix, S Hald, L Reinert, M K Magnusson, J Agnholt
PURPOSE: Vitamin D may induce tolerance in the intestinal immune system and has been shown to regulate the phenotype of tolerogenic intestinal dendritic cells (DCs) in vitro. It is unknown whether vitamin D supplementation affects human intestinal DCs in vivo, and we aimed to investigate the tolerability and effect on intestinal CD103(+)DCs of high-dose vitamin D3 treatment in healthy subjects. METHODS: Ten healthy subjects received a total of 480,000 IU oral vitamin D3 over 15 days and colonic biopsies were obtained before and after intervention by endoscopy...
September 14, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28870263/effect-of-maternal-vitamin-d3-supplementation-on-maternal-health-birth-outcomes-and-infant-growth-among-hiv-infected-tanzanian-pregnant-women-study-protocol-for-a-randomized-controlled-trial
#2
Christopher R Sudfeld, Karim P Manji, Christopher P Duggan, Said Aboud, Alfa Muhihi, David M Sando, Fadhlun M Alwy Al-Beity, Molin Wang, Wafaie W Fawzi
BACKGROUND: Vitamin D has significant immunomodulatory effects on both adaptive and innate immune responses. Observational studies indicate that adults infected with HIV with low vitamin D status may be at increased risk of mortality, pulmonary tuberculosis, and HIV disease progression. Growing observational evidence also suggests that low vitamin D status in pregnancy may increase the risk of adverse birth and infant health outcomes. As a result, antiretroviral therapy (ART) adjunct vitamin D3 supplementation may improve the health of HIV-infected pregnant women and their children...
September 4, 2017: Trials
https://www.readbyqxmd.com/read/28835974/-hypercalcemic-crisis-and-hypocalcemic-tetany
#3
REVIEW
C Kasperk
A serum calcium level >3.5 mmol/l together with clinical symptoms such as muscle weakness, fatigue, nausea, vomiting, pancreatitis or even coma are characteristic for a hypercalcemic crisis (HC). Primary hyperparathyroidism (1HPT) and malignancy-associated hypercalcemia are the most frequent causal diseases for a HC. The analysis of serum levels for calcium, phosphorous, intact parathyroid hormone, electrophoresis and renal function parameters indicate which further radiological, scintigraphic or serum diagnostic steps are adequate to identify the cause of the patient's acute situation (i...
August 23, 2017: Der Internist
https://www.readbyqxmd.com/read/28814738/identification-of-novel-non-secosteroidal-vitamin-d-receptor-agonists-with-potent-cardioprotective-effects-and%C3%A2-%C3%AF-%C3%AF-devoid-of-hypercalcemia
#4
Santosh A Khedkar, Mohammed A Samad, Sangita Choudhury, Ji Yoo Lee, Dongsheng Zhang, Ravi I Thadhani, S Ananth Karumanchi, Alan C Rigby, Peter M Kang
Vitamin D regulates many biological processes, but its clinical utility is limited by its hypercalcemic effect. Using a virtual screening platform to search novel chemical probes that activate the vitamin D signaling, we report discovery of novel non-steroidal small-molecule compounds that activate the vitamin D receptor (VDR), but are devoid of hypercalcemia. A lead compound (known as VDR 4-1) demonstrated potent transcriptional activities in a VDR reporter gene assay, and significantly ameliorated cardiac hypertrophy in cell culture studies and in animal models...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801091/how-much-is-too-much-two-contrasting-cases-of-excessive-vitamin-d-supplementation
#5
Sollip Kim, Laura D Stephens, Robert L Fitzgerald
BACKGROUND: In this report, we describe 2 contrasting cases of hypervitaminosis D. CASE PRESENTATION: Patient 1 was a 75-y old man who developed symptomatic hypercalcemia (peak serum calcium concentration of 15.3mg/dl; reference range: 8.5-10.6mg/dl), cardiac injury, and a high total serum vitamin D concentration of 243ng/ml (30-80ng/ml) as a result of daily consumption of prescribed 50,000IU ergocalciferol (vitamin D2) and 500mg calcium-citrate for 1y. Patient 2 was a 60-y old woman who consumed 40,000IU of cholecalciferol (vitamin D3) daily for >10months with a peak total serum vitamin D concentration of 479ng/ml (30-80ng/ml), but did not present with symptoms related to vitamin D toxicity...
October 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28647736/no-severe-hypercalcemia-with-daily-vitamin-d3-supplementation-of-up-to-30-%C3%A2%C2%B5g-during-the-first-year-of-life
#6
Saara Valkama, Elisa Holmlund-Suila, Maria Enlund-Cerullo, Jenni Rosendahl, Helena Hauta-Alus, Otto Helve, Timo Hytinantti, Heli Viljakainen, Sture Andersson, Outi Mäkitie
BACKGROUND: Vitamin D supplementation is widely recommended for infants, but the optimal dose remains unclear. High intake may result in hypercalcemia. METHODS: We evaluated the incidence of hypercalcemia during the first year of life in a cohort of 987 healthy children who received 10 or 30 μg of vitamin D3 supplementation daily. Ionized calcium (Ca-ion) was analyzed at 6 and 12 months, and serum 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) concentration at 12 months...
2017: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/28591703/vitamin-d-receptor-activation-reduces-vcap-xenograft-tumor-growth-and-counteracts-erg-activity-despite-induction-of-tmprss2-erg
#7
Justin M Roberts, Rebeca San Martin, D Badrajee Piyarathna, James G MacKrell, Guilherme V Rocha, Jeffery A Dodge, Cristian Coarfa, Venkatesh Krishnan, David R Rowley, Nancy L Weigel
Whether vitamin D is chemopreventive and/or has potential therapeutically in prostate cancer is unresolved. One confounding factor is that many prostate cancers express a TMPRSS2:ERG fusion gene whose expression is increased both by androgens and by vitamin D receptor (VDR) activation. Two challenges that limit VDR agonist use clinically are hypercalcemia and the cooperation of VDR with ERG to hyper-induce the 1α,25-dihydroxyvitamin D3 metabolizing enzyme, CYP24A1, thus reducing VDR activity. Using the VCaP TMPRSS2:ERG positive cell line as a model, we found that a nonsecosteroidal CYP24A1 resistant VDR agonist, VDRM2, substantially reduces growth of xenograft tumors without inducing hypercalcemia...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28458767/evaluation-of-vitamin-d3-intakes-up-to-15-000-international-units-day-and-serum-25-hydroxyvitamin-d-concentrations-up-to-300-nmol-l-on-calcium-metabolism-in-a-community-setting
#8
S M Kimball, N Mirhosseini, M F Holick
Supplementation by the general public with vitamin D at doses above the Tolerable Upper Level of Intake (UL) is becoming quite common. The objective of the current analysis was to characterize the effect of vitamin D supplementation at doses up to 15,000 IU/d in a community-based program on vitamin D status, calcium homeostasis as well as on kidney, liver and immune function. We evaluated data collected for 3,882 participants in a community program for whom there were blood measurements at program entry and at follow-up within 6-18 months between 2013 and 2015...
2017: Dermato-endocrinology
https://www.readbyqxmd.com/read/28448545/vitamin-d3-induced-hypercalcemia-increases-carbon-tetrachloride-induced-hepatotoxicity-through-elevated-oxidative-stress-in-mice
#9
Hiroki Yoshioka, Haruki Usuda, Nobuhiko Miura, Nobuyuki Fukuishi, Tsunemasa Nonogaki, Satomi Onosaka
The aim of this study was to determine whether calcium potentiates acute carbon tetrachloride (CCl4) -induced toxicity. Elevated calcium levels were induced in mice by pre-treatment with cholecalciferol (vitamin D3; V.D3), a compound that has previously been shown to induce hypercalcemia in human and animal models. As seen previously, mice injected with CCl4 exhibited increased plasma levels of alanine aminotransferase, aspartate aminotransferase, and creatinine; transient body weight loss; and increased lipid peroxidation along with decreased total antioxidant power, glutathione, ATP, and NADPH...
2017: PloS One
https://www.readbyqxmd.com/read/28433267/dose-response-effects-of-supplementation-with-calcifediol-on-serum-25-hydroxyvitamin-d-status-and-its-metabolites-a-randomized-controlled-trial-in-older-adults
#10
Anouk M M Vaes, Michael Tieland, Margot F de Regt, Jonas Wittwer, Luc J C van Loon, Lisette C P G M de Groot
BACKGROUND & AIMS: Oral supplementation with vitamin D is recommended for older adults to maintain a sufficient 25-hydroxyvitamin D (25(OH)D) status throughout the year. While supplementation with vitamin D2 or D3 is most common, alternative treatment regimens exist which require further investigation with respect to increasing 25(OH)D concentration. We investigated the dose-response effects of supplementation with calcifediol compared to vitamin D3 and assessed the dose which results in mean serum 25(OH)D3 concentrations between 75 and 100 nmol/L...
March 31, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28345770/effect-of-1-25-oh-2-d3-and-20-oh-d3-on-interleukin-1%C3%AE-stimulated-interleukin-6-and-8-production-by-human-gingival-fibroblasts
#11
V Nakashyan, D A Tipton, A Karydis, R Livada, S H Stein
BACKGROUND AND OBJECTIVE: Vitamin D-1,25(OH)2 D3 or 1,25D3-maintains healthy osseous tissue, stimulates the production of the antimicrobial peptide cathelicidin and has anti-inflammatory effects, but it can cause hypercalcemia. Evidence links diminished serum levels of 1,25D3 with increased gingival inflammation. Periodontitis progression is associated with increased local production of inflammatory mediators by immune cells and gingival fibroblasts. These include interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8, both regulated by signaling pathways, including NF-κB and MAPK/AP-1...
March 27, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28324001/cyp3a4-induction-by-rifampin-an-alternative-pathway-for-vitamin-d-inactivation-in-patients-with-cyp24a1-mutations
#12
Colin Patrick Hawkes, Dong Li, Hakon Hakonarson, Kevin E Meyers, Kenneth E Thummel, Michael A Levine
Context: The P450 enzyme CYP24A1 is the principal inactivator of vitamin D metabolites. Biallelic loss-of-function mutations in CYP24A1 are associated with elevated serum levels of 1,25-dihydroxyvitamin D3 with consequent hypercalcemia and hypercalciuria and represent the most common form of idiopathic infantile hypercalcemia (IIH). Current management strategies for this condition include a low-calcium diet, reduced dietary vitamin D intake, and limited sunlight exposure. CYP3A4 is a P450 enzyme that inactivates many drugs and xenobiotics and may represent an alternative pathway for inactivation of vitamin D metabolites...
May 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28304097/improved-screening-test-for-idiopathic-infantile-hypercalcemia-confirms-residual-levels-of-serum-24-25-oh-2-d3-in-affected-patients
#13
Martin Kaufmann, Nicole Morse, Billy Joe Molloy, Donald P Cooper, Karl Peter Schlingmann, Arnaud Molin, Marie Laure Kottler, J Christopher Gallagher, Laura Armas, Glenville Jones
CYP24A1 mutations are now accepted as a cause of idiopathic infantile hypercalcemia (IIH). A rapid liquid-chromatography tandem mass spectrometry (LC-MS/MS)-based blood test enabling measurement of the 25-OH-D3 :24,25-(OH)2 D3 ratio (R) can identify IIH patients on the basis of reduced C24-hydroxylation of 25-OH-D3 by CYP24A1 in vivo. Although values of this ratio are significantly elevated in IIH, somewhat surprisingly, serum 24,25-(OH)2 D3 remains detectable. The current study explores possible explanations for this including: residual CYP24A1 enzyme activity in individuals with certain CYP24A1 genotypes, expression of alternative C24-hydroxylases, and the possibility of isobaric contamination of the 24,25-(OH)2 D3 peak on LC-MS/MS...
July 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28294593/effect-of-vitamin-d-replacement-in-primary-hyperparathyroidism-with-concurrent-vitamin-d-deficiency-a-systematic-review-and-meta-analysis
#14
Huai Heng Loh, Lee Ling Lim, Anne Yee, Huai Seng Loh, Shireene R Vethakkan
INTRODUCTION: We conducted a meta-analysis to assess the effects of vitamin D replacement on biochemical and skeletal parameters in subjects with mild primary hyperparathyroidism (PHPT) and coexistent vitamin D deficiency. EVIDENCE ACQUISITION: A systematic search of all English-language medical literature published from 1980 till May 2016 using Pubmed, Embase and Ovid was performed. Nine observational studies were evaluated after fulfilling the inclusion and exclusion criteria...
March 14, 2017: Minerva Endocrinologica
https://www.readbyqxmd.com/read/28183335/efficacy-of-vitamin-d3-supplementation-in-reducing-incidence-of-pulmonary-tuberculosis-and-mortality-among-hiv-infected-tanzanian-adults-initiating-antiretroviral-therapy-study-protocol-for-a-randomized-controlled-trial
#15
Christopher R Sudfeld, Ferdinand Mugusi, Said Aboud, Tumaini J Nagu, Molin Wang, Wafaie W Fawzi
BACKGROUND: HIV-infected adults initiating antiretroviral therapy (ART) in sub-Saharan Africa continue to experience high rates of morbidity and mortality during the initial months of treatment. Observational studies in high-income and resource-limited settings indicate that HIV-infected adults with low vitamin D levels may be at increased risk of mortality, HIV disease progression, and incidence of pulmonary tuberculosis (TB). As a result, vitamin D3 supplementation may improve survival and treatment outcomes for HIV-infected adults initiating ART...
February 10, 2017: Trials
https://www.readbyqxmd.com/read/28174131/application-of-vitamin-d-and-vitamin-d-analogs-in-acute-myelogenous-leukemia
#16
REVIEW
Huynh Cao, Yi Xu, Rosalia de Necochea-Campion, David J Baylink, Kimberly J Payne, Xiaolei Tang, Christina Ratanatharathorn, Yong Ji, Saied Mirshahidi, Chien-Shing Chen
Acute myeloid leukemia (AML) is characterized by the accumulation of malignant, transformed immature hematopoietic myeloid precursors that have lost their ability to differentiate and proliferate normally. Current treatment for AML requires intensive cytotoxic chemotherapy and results in significant morbidity and mortality, especially in older patients. Effective and better-tolerated treatment is urgently needed. Studies have shown that 1α,25-dihydroxyvitamin D3 (1,25-D3, active VD3) or vitamin D analogs (VDAs) can potently differentiate AML cells in vitro and ex vivo, which led to early clinical trials in AML and myelodysplastic syndrome patients...
June 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28109821/calcium-pyrophosphate-deposition-disease-revealing-a-hypersensitivity-to-vitamin-d
#17
Pauline Baudart, Arnaud Molin, Johann Cesini, Glenville Jones, Martin Kaufmann, Marie Laure Kottler, Christian Marcelli
OBJECTIVE: Hypersensitivity to vitamin D (HVD) due to a loss of function mutation of the CYP24A1 gene, which encodes vitamin D catabolizing enzyme was initially described as a cause of acute hypercalcemia in children and chronic renal diseases in adults. METHODS: We describe the first case of a patient presenting a calcium pyrophosphate deposition disease (CPDD) revealing a HVD. RESULTS: An abnormality of phospho-calcic metabolism was discovered during the course of an etiological workup for CPDD in a 52-year-old patient...
May 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28077342/can-stoss-therapy-be-used-in-children-with-vitamin-d-deficiency-or-insufficiency-without-rickets
#18
Cemil Koçyiğit, Gönül Çatlı, Gülberat İnce, Elif Büşra Özkan, Bumin Nuri Dündar
OBJECTIVE: Stoss vitamin D treatment has been recommended for its non-skeletal benefits in adults, but there is a lack of data on the optimal dose of vitamin D stoss therapy in children with vitamin D deficiency/insufficiency without rickets. This study aimed to compare efficiency/side effects of two different stoss therapy regimens (10 000 IU/kg and 300 000 IU vitamin D3) administered in children with vitamin D deficiency/insufficiency without rickets. METHODS: Sixty-four children who had vitamin D deficiency/insufficiency were studied...
June 1, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/28012936/results-of-daily-oral-dosing-with-up-to-60-000-international-units-iu-of-vitamin-d3-for-2-to-6-years-in-3-adult-males
#19
Patrick McCullough, Jeffrey Amend
In the 1930's and 1940's, vitamin D was reported to be an effective treatment for a number of diseases, including asthma, psoriasis, rheumatoid arthritis, rickets and tuberculosis. High doses were used, 60,000 to 300,000 IU a day for asthma, and 200,000 to 600,000 IU a day for rheumatoid arthritis. Toxicity from hypercalcemia occurred after prolonged oral dosing with these supraphysiologic doses. Assays for measuring vitamin D in the blood were not available, and blood levels of vitamin D associated with hypercalcemia were unknown...
December 21, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27919743/dual-antiplasmodial-activity-of-vitamin-d3-and-its-analog-22-oxacalcitriol-by-direct-and-indirect-mechanisms
#20
Kiichi Yamamoto, Moritoshi Iwagami, Takenori Seki, Shigeyuki Kano, Nobuo Ota, Manabu Ato
Recent evidence suggests that 1α,25-dihydroxyvitamin D3 (calcitriol, VD3), the active form of vitamin D (VD), can inhibit the proliferation of microorganisms. In the present study, we conducted in vitro experiments and utilized in vivo murine models to investigate the antimalarial activity of VD3 and its analog, 22-oxacalcitriol (22-OCT), which was designed to cause less hypercalcemia than VD3. VD3 and 22-OCT treatments effectively resolved a Plasmodium chabaudi (Pc) infection in wild-type mice. Reduced parasitemia was observed during the acute phase of infection in the presence of VD3 and 22-OCT, followed by a delayed peak during the chronic stage of infection...
April 2017: Parasitology International
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