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Vitamin D3 AND hypercalcemia

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https://www.readbyqxmd.com/read/29517453/suspected-hypervitaminosis-d-in-red-rumped-agouti-dasyprocta-leporina-receiving-a-commercial-rodent-diet
#1
Kadie M Anderson, Albert Lewandowski, Patricia M Dennis
An 8 yr, intact male red-rumped agouti ( Dasyprocta leporina) was evaluated for weight loss. Examination revealed poor body condition, hypercalcemia, elevated serum 25-hydroxyvitamin D, metastatic calcification of soft tissues, and hyperechoic kidneys. The diet, formulated for laboratory rodents, contained elevated levels of vitamin D3 . Histopathology from a female conspecific that died 5 mo prior identified dystrophic mineralization and nephrosclerosis, suggestive of a vitamin D3 toxicity. The male agouti responded well to a dietary reduction in vitamin D3 and calcium...
March 2018: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/29515772/the-c-raf-modulator-rrd-251-enhances-nuclear-c-raf-gsk-3-vdr-axis-signaling-and-augments-1-25-dihydroxyvitamin-d3-induced-differentiation-of-hl-60-myeloblastic-leukemia-cells
#2
Harrison T Supnick, Rodica P Bunaciu, Andrew Yen
Differentiation therapy is used in cancer treatment. Epidemiologic studies showed that higher vitamin D levels are associated with reduced cancer risks. However, the therapeutic doses needed for differentiation are accompanied by hypercalcemia and intolerable pathological sequelae. In the present work we evaluated if RRD-251, a small-molecule, can enhance vitamin D3-induced differentiation of leukemic cells, in the hope of decreasing the needed vitamin D3-dose. We demonstrate that RRD-251 enhances vitamin D3-induced differentiation of leukemic cells, the enrichment of the c-Raf kinase in the nucleus, the binding of nuclear c-Raf to GSK-3, increased phosphorylation of GSK-3 ser 21/9 inhibitory sites, and the binding of GSK-3 to VDR, where GSK-3 inhibition is known to enhance transcriptional activation by VDR...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29476878/low-systemic-exposure-and-calcemic-effect-of-calcipotriol-betamethasone-ointment-in-rats-with-imiquimod-induced-psoriasis-like-dermatitis
#3
Kyosuke Satake, Toru Amano, Tadao Okamoto
Vitamin D3 (VD3 ) analogues-containing ointments are known to occasionally cause hypercalcemia in psoriasis patients, and the frequency of hypercalcemia is suggested to vary based on the VD3 analogue used. In this study, to address the differences in calcemic effects of VD3 -containing ointments, the calcemic effects of marketed VD3 -containing ointments, including calcipotriol (Cal), maxacalcitol (Max), tacalcitol (Tac), calcipotriol/betamethasone dipropionate (Cal/BDP) and maxacalcitol/betamethasone butyrate propionate (Max/BBP) ointments, were evaluated in a rat model of imiquimod-induced dermatitis...
February 21, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29275531/renal-phosphate-handling-and-inherited-disorders-of-phosphate-reabsorption-an-update
#4
REVIEW
Carsten A Wagner, Isabel Rubio-Aliaga, Nati Hernando
Renal phosphate handling critically determines plasma phosphate and whole body phosphate levels. Filtered phosphate is mostly reabsorbed by Na+ -dependent phosphate transporters located in the brush border membrane of the proximal tubule: NaPi-IIa (SLC34A1), NaPi-IIc (SLC34A3), and Pit-2 (SLC20A2). Here we review new evidence for the role and relevance of these transporters in inherited disorders of renal phosphate handling. The importance of NaPi-IIa and NaPi-IIc for renal phosphate reabsorption and mineral homeostasis has been highlighted by the identification of mutations in these transporters in a subset of patients with infantile idiopathic hypercalcemia and patients with hereditary hypophosphatemic rickets with hypercalciuria...
December 23, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29243851/alterations-in-gene-expression-in-vitamin-d-deficiency-down-regulation-of-liver-cyp7a1-and-renal-oat3-in-mice
#5
Holly P Quach, Keumhan Noh, Stacie Y Hoi, Adrie Bruinsma, Geny M M Groothuis, Albert P Li, Edwin C Y Chow, K Sandy Pang
The vitamin D-deficient model, established in the C57BL/6 mouse after 8 weeks of feeding vitamin D-deficient diets in the absence or presence of added calcium, was found associated with elevated levels of plasma parathyroid hormone (PTH) and plasma and liver cholesterol, and a reduction in cholesterol 7α-hydroxylase (Cyp7a1, rate-limiting enzyme for cholesterol metabolism) and renal Oat3 mRNA/protein expression levels. However, there was no change in plasma calcium and phosphate levels. Appraisal of the liver revealed an up-regulation of mRNA expressions of the small heterodimer partner (Shp) and attenuation of Cyp7a1, which contributed to hypercholesterolemia in vitamin D-deficiency...
February 2018: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29080636/genetic-diseases-of-vitamin-d-metabolizing-enzymes
#6
REVIEW
Glenville Jones, Marie Laure Kottler, Karl Peter Schlingmann
Vitamin D metabolism involves 3 highly specific cytochrome P450 (CYP) enzymes (25-hydroxylase, 1α-hydroxylase, and 24-hydroxylase) involved in the activation of vitamin D3 to the hormonal form, 1,25-(OH)2D3, and the inactivation of 1,25-(OH)2D3 to biliary excretory products. Mutations of the activating enzymes CYP2R1 and CYP27B1 cause lack of normal 1,25-(OH)2D3 synthesis and result in rickets whereas mutations of the inactivating enzyme CYP24A1 cause build-up of excess 1,25-(OH)2D3 and result in hypercalcemia, nephrolithiasis, and nephrocalcinosis...
December 2017: Endocrinology and Metabolism Clinics of North America
https://www.readbyqxmd.com/read/29076379/low-incidence-of-hypercalcemia-following-combined-calcipotriol-hydrate-betamethasone-dipropionate-ointment-treatment-in-japanese-patients-with-severe-psoriasis-vulgaris
#7
Akimichi Morita, Shinnosuke Muramatsu, Ryoji Kubo, Kyoko Ikumi, Yoko Sagawa, Chiyo Saito, Kan Torii, Emi Nishida
PURPOSE: Topical active vitamin D3 application alone or in combination with topical steroid application is widely used to treat psoriasis. In Japan, combined calcipotriol hydrate/betamethasone dipropionate ointment has been used for patients with psoriasis vulgaris since September 2014. Current evidence regarding the incidence of hypercalcemia due to the use of this combination product, however, is insufficient. We evaluated the incidence of hypercalcemia following combined calcipotriol hydrate/betamethasone dipropionate ointment in patients with severe psoriasis vulgaris...
January 10, 2018: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29075077/bone-histo-morphology-in-chronic-kidney-disease-mineral-bone-disorder
#8
Khuraijam Bembem, Tejinder Singh, Narinder Pal Singh, Alpana Saxena, Shyama Lata Jain
Chronic Kidney Disease-Mineral Bone Disorder(CKD-MBD) is a systemic disorder of the mineral and bone metabolism seen in patients with Chronic Kidney Disease(CKD). It is manifested by either one or a combination of the following: (a) Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism. (b) Abnormalities in bone turnover, mineralization, volume, linear growth, or strength. (c) Vascular or other soft- tissue calcification. Renal osteodystrophy measures the skeletal component of CKD-MBD. To study the histomorphology of bone marrow biopsy in patients with CKD-MBD and correlate the histological features of bone biopsy with the clinicobiochemical parameters...
December 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29074825/-update-on-recent-progress-in-vitamin-d-research-vitamin-d-receptor-and-the-nuclear-receptor-superfamily
#9
REVIEW
Makoto Makishima
The vitamin D receptor(VDR)is a ligand-dependent transcription factor of the nuclear receptor superfamily. VDR belongs to the NR1I subfamily along with other nuclear receptors involved in xenobiotic metabolism, such as pregnane X receptor. The oxysterol receptors liver X receptors α/β and the bile acid receptor farnesoid X receptor belong to the NR1H subfamily, which are closely related to the NR1I subfamily. NR1I and NR1H nuclear receptors form heterodimers with retinoid X receptor. The active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ], acts as a physiological VDR ligand, and regulates various physiological processes, including calcium and bone metabolism, cellular growth and differentiation, immunity, and cardiovascular function...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/29030554/hdx-reveals-the-conformational-dynamics-of-dna-sequence-specific-vdr-co-activator-interactions
#10
Jie Zheng, Mi Ra Chang, Ryan E Stites, Yong Wang, John B Bruning, Bruce D Pascal, Scott J Novick, Ruben D Garcia-Ordonez, Keith R Stayrook, Michael J Chalmers, Jeffrey A Dodge, Patrick R Griffin
The vitamin D receptor/retinoid X receptor-α heterodimer (VDRRXRα) regulates bone mineralization via transcriptional control of osteocalcin (BGLAP) gene and is the receptor for 1α,25-dihydroxyvitamin D3 (1,25D3). However, supra-physiological levels of 1,25D3 activates the calcium-regulating gene TRPV6 leading to hypercalcemia. An approach to attenuate this adverse effect is to develop selective VDR modulators (VDRMs) that differentially activate BGLAP but not TRPV6. Here we present structural insight for the action of a VDRM compared with agonists by employing hydrogen/deuterium exchange...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28913556/high-dose-vitamin-d3-supplementation-decreases-the-number-of-colonic-cd103-dendritic-cells-in-healthy-subjects
#11
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
#12
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
#13
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...
October 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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