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1,25-dihydroxyvitamin d

Bart L Clarke, Tamara J Vokes, John P Bilezikian, Dolores M Shoback, Hjalmar Lagast, Michael Mannstadt
In hypoparathyroidism, inappropriately low levels of parathyroid hormone lead to unbalanced mineral homeostasis. The objective of this study was to determine the effect of recombinant human parathyroid hormone, rhPTH(1-84), on phosphate and vitamin D metabolite levels in patients with hypoparathyroidism. Following pretreatment optimization of calcium and vitamin D doses, 124 patients in a phase III, 24-week, randomized, double-blind, placebo-controlled study of adults with hypoparathyroidism received subcutaneous injections of placebo or rhPTH(1-84) (50 µg/day, titrated to 75 and then 100 µg/day, to permit reductions in oral calcium and active vitamin D doses while maintaining serum calcium within 2...
October 12, 2016: Endocrine
Daijo Inaguma, Hibiki Shinjo, Akihito Tanaka, Eri Ito, Naoki Kamegai, Akiko Kato, Minami Mizutani, Hiroya Shimogushi, Yasuhiro Otsuka, Asami Takeda, Midori Hasegawa, Yukio Yuzawa
OBJECTIVE: To investigate the correlation between serum 1,25-dihydroxyvitamin D (1,25D) levels and left atrial diameter (LAD) using echocardiography in pre-dialysis chronic kidney disease (CKD). SUBJECTS AND METHODS: From an initial population of 487 patients (109 met the exclusion criteria), a total of 378 patients with CKD stage 3a - 5 who had not undergone dialysis or kidney transplantation were included in the study. The relationship between serum 1,25D levels and LAD was examined...
November 2016: Clinical Nephrology
Lamia Ysmail-Dahlouk, Wafa Nouari, Mourad Aribi
BACKGROUND: Type 1 diabetes (T1D) is associated with an imbalance between inflammation and repair. Recently, the biologically active form of vitamin D3, i.e. 1,25(OH)2D3, has been reported to have potent immunomodulatory effects on both innate and adaptive immune cells, as well as on the production of their specific cytokines. METHODS: We examined the effect of 1,25(OH)2D3 on the production of proinflammatory Th1/Th17 and anti-inflammatory Th2/Treg related cytokines, as well as on the phosphorylation of monocyte-expressed STAT4 and STAT6 at the recent-onset human T1D...
October 4, 2016: Immunology Letters
J J Todd, E M McSorley, L K Pourshahidi, S M Madigan, W Crowe, E J Laird, M Healy, A McNeilly, P J Magee
Vitamin D inadequacy [total 25(OH)D <50 nmol/L] is widespread in athletes. The biologically active metabolite, 1,25-dihydroxyvitamin D, may be involved in regulating inflammation although in vitro findings have not been consistently replicated in human intervention trials. This study, conducted at a latitude of 55°N, aimed to assess inflammatory biomarkers in Gaelic footballers before and after a wintertime vitamin D3 intervention. Samples from a 12-week double-blind, randomized, placebo-controlled trial, in which 42 Gaelic footballers received 3000 IU (75 μg) vitamin D3 daily or placebo via oral spray solutions, were analysed for a range of inflammatory biomarkers...
October 5, 2016: Scandinavian Journal of Medicine & Science in Sports
Long Zhang, Adrienne Tin, Todd Brown, Joseph B Margolick, Mallory D Witt, Frank J Palella, Lawrence Kingsley, Andrew Hoofnagle, Lisa Jacobson, Alison Abraham
We evaluated associations of serum 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) levels in a cohort of HIV-infected and -uninfected men at risk for infection in the United States. Stored samples collected between 1999 and 2008 were tested for vitamin D metabolites between 2014 and 2015. Vitamin D deficiency was defined as a serum concentration of 25[OH]D < 20ng/mL. Multivariate models were used to assess associations of various demographic and clinical factors with vitamin D status...
October 4, 2016: AIDS Research and Human Retroviruses
Kamlesh Bhatt, Wasiulla Rafi, Neel Shah, Sylvia Christakos, Padmini Salgame
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...
October 4, 2016: Scientific Reports
Fatouma Alimirah, Xinjian Peng, Akash Gupta, Liang Yuan, JoEllen Welsh, Michele Cleary, Rajendra G Mehta
The vitamin D receptor (VDR), and its ligand 1α,25-dihydroxyvitamin D3 (1,25D3) prevent breast cancer development and progression, yet the molecular mechanisms governing this are unclear. MicroRNAs (miRNAs) on the other hand, promote or inhibit breast cancer growth. To understand how VDR regulates miRNAs, we compared miRNA expression of wild-type (WT) and VDR knockout (VDRKO) breast cancer cells by a Mouse Breast Cancer miRNA PCR array. Compared to VDR WT cells, expressions of miR-214, miR-199a-3p and miR-199a-5p of the miR-199a/miR-214 cluster were 42, 15, and 10 fold higher in VDRKO cells respectively...
September 27, 2016: Experimental Cell Research
Máté Fort Molnár, Rita Török, Levente Szalárdy, Evelin Sümegi, László Vécsei, Péter Klivényi
Huntington's disease is an autosomal dominant progressive neurodegenerative disease, which results in a decreased quality of life and an early death. A high prevalence of vitamin D deficiency was first described in a 2013 study in patients with manifest Huntington's disease, where serum vitamin D level was found to be associated with motor capabilities of the patients. Our objective was to investigate the effect of a high-dose vitamin D3 supplementation on a transgenic mouse model of Huntington's disease. Our study was performed on N171-82Q Huntington's disease transgenic mice in age- and gender-matched groups...
2016: Acta Neurobiologiae Experimentalis
Shunsuke Goto, Hideki Fujii, Keiji Kono, Kentaro Watanabe, Kentaro Nakai, Shinichi Nishi
Fibroblast growth factor 23 (FGF23) is regulated by sustained phosphate supplementation and restriction. However, few studies have investigated FGF23 levels in patients with Fanconi syndrome. Therefore, we evaluated intact and C-terminal FGF23 and FGF23-associated parameters in four patients with Fanconi syndrome. Serum intact and C-terminal FGF23 levels were extremely low. Although serum phosphate and 1,25-dihydroxyvitamin D levels improved to or above the normal range within 1 year of treatment with oral phosphate and calcitriol, serum FGF23 levels remained low...
October 2016: Clinical Kidney Journal
Geoffrey N Hendy, Lucie Canaff
The human calcium-sensing receptor gene (CASR) has 8 exons, and localizes to chromosome 3q. Exons 1A and 1B encode alternative 5'-untranslated regions (UTRs) that splice to exon 2 encoding the AUG initiation codon. Exons 2-7 encode the CaSR protein of 1078 amino acids. Promoter P1 has TATA and CCAAT boxes upstream of exon 1A, and promoter P2 has Sp1/3 motifs at the start site of exon 1B. Exon 1A transcripts from the P1 promoter are reduced in parathyroid tumors and colon carcinomas. Studies of colon carcinomas and neuroblastomas have emphasized the importance of epigenetic changes-promoter methylation of the GC-rich P2 promoter, histone acetylation-as well as involvement of microRNAs in bringing about CASR gene silencing and reduced CaSR expression...
2016: Frontiers in Physiology
Maria Matar, Laila Al-Shaar, Joyce Maalouf, Mona Nabulsi, Asma Arabi, Mahmoud Choucair, Hani Tamim, Ghada El-Hajj Fuleihan
BACKGROUND: Little is known about the changes in calciotropic hormones during puberty and their relationship to bone mass during this critical period for skeletal accretion. OBJECTIVES: Investigate changes in calciotropic hormones, IGF1, body composition and their associations with bone metabolism in adolescents. METHODS: Post-hoc analyses from data on 335 healthy school children, ages 10-17 years, with hypovitaminosis D, who participated in a vitamin D randomized controlled trial...
September 27, 2016: Journal of Clinical Endocrinology and Metabolism
Rui Zhou, Juw Won Park, Rene F Chun, Thomas S Lisse, Alejandro J Garcia, Kathryn Zavala, Jessica L Sea, Zhi-Xiang Lu, Jianzhong Xu, Yi Xing, John S Adams, Martin Hewison
Traditionally recognized as an RNA splicing regulator, heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC1/C2) can also bind to double-stranded DNA and function in trans as a vitamin D response element (VDRE)-binding protein. As such, hnRNPC1/C2 may couple transcription induced by the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) with subsequent RNA splicing. In MG63 osteoblastic cells, increased expression of the 1,25(OH)2D target gene CYP24A1 involved immunoprecipitation of hnRNPC1/C2 with CYP24A1 chromatin and RNA...
September 26, 2016: Nucleic Acids Research
Mohammad Reza Shiri-Shahsavar, Abbas Mirshafiee, Karim Parastouei, Abbas Ebrahimi-Kalan, Saeed Yekaninejad, Farid Soleymani, Reza Chahardoli, Ramin Mazaheri Nezhad Fard, Ali Akbar Saboor-Yaraghi
Vitamins are immunologically interesting due to their significant immunomodulatory activities. Experimental autoimmune encephalomyelitis (EAE) is one of the most commonly used experimental models for studying autoimmune disorder in multiple sclerosis (MS). The aim of this study was to evaluate the protective and ameliorative effects of novel combination of all-trans retinoic acid (ATRA), 1,25-dihydroxyvitamin D3 (D3), and docosahexaenoic acid (DHA) on EAE-specific determinants and target gene expressions. Mice were randomly categorized into three groups before EAE induction [non-treated EAE (Group E), treated EAE (Group T), and healthy mice (Group H)]...
September 19, 2016: Journal of Molecular Neuroscience: MN
Masumi Kondo, Masao Toyoda, Han Miyatake, Eitaro Tanaka, Masahiro Koizumi, Hirotaka Komaba, Moritsugu Kimura, Tomoya Umezono, Masafumi Fukagawa
Objective The purpose of this study was to measure serum 25-hydroxyvitamin D [25(OH)D] levels in Japanese patients with diabetic nephropathy and determine the relationship between 25(OH)D concentrations and various factors. Methods The study subjects included 442 patients with type 2 diabetes. Their serum levels of creatinine, HbA1c, intact-parathyroid hormone, urinary albumin, 25(OH)D, and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured and their estimated glomerular filtration rate (eGFR) was determined...
2016: Internal Medicine
Xiao-Li Dong, Si-Si Cao, Li-Ping Zhou, Liya Denney, Man-Sau Wong, Hao-Tian Feng
Our previous studies found that different extracts or fractions of Fructus ligustri lucidi (FLL) played different roles in altering the regulation of bone and mineral metabolism in different animal models. The present study was designed to compare the actions of FLL ethanol (EE) and water extracts (WE) on bone and mineral metabolism in a 6-month-old mature ovariectomized (OVX) rat model. Our results showed that FLL extracts did not significantly improve systematic Ca balance in mature OVX rats. However, EE, but not WE treatment, significantly increased serum 1,25(OH)2D3 levels in mature OVX rats...
2016: American Journal of Chinese Medicine
Teppei Sakoh, Masaru Nakayama, Takuya Tsuchihashi, Ryota Yoshitomi, Shigeru Tanaka, Eisuke Katafuchi, Akiko Fukui, Yui Shikuwa, Naohiko Anzai, Takanari Kitazono, Kazuhiko Tsuruya
OBJECTIVE: In patients with preserved kidney function, a positive association of fibroblast growth factor 23 (FGF23) with serum uric acid (SUA) has been reported; however, the relationship in overall chronic kidney disease (CKD) patients has not been investigated. No report has examined the relationship between FGF23 and uric acid clearance (CUA). The aim of the present study was to determine whether FGF23 is independently associated with urate metabolism in patients with CKD stages 1-5...
October 2016: Metabolism: Clinical and Experimental
Wenjie Liu, Huiyuan Li, Yating Hao, Yang Li, Mingen Lv, Feng Xue, Xiaofan Liu, Lei Zhang, Renchi Yang
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease. 1α, 25-dihydroxyvitamin D3 [1,25(OH)2D3] and vitamin D receptor (VDR) play important immune-suppressive roles in immune system. It has been reported that serum 1,25(OH)2D3 were lower in ITP patients. In this study, we evaluated local 1,25(OH)2D3 level and VDR mRNA expression further, and determined whether 1,25(OH)2D3/VDR were correlated with T cell dysfunction in ITP patients. We found that 1,25(OH)2D3/VDR levels were decreased in active ITP patients, and 1,25(OH)2D3 had significant anti-inflammatory effects on ITP patients, including both anti-proliferation of peripheral blood mononuclear cells (PBMCs) and reversing the abnormal T cells polarization...
October 2016: Molecular Immunology
Peter J Tebben, Ravinder J Singh, Rajiv Kumar
Hypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D...
October 2016: Endocrine Reviews
Rong Li, Jinsu Huang, Meili Ma, Yuqing Lou, Yanwei Zhang, Lixia Wu, David W Chang, Picheng Zhao, Qianggang Dong, Xifeng Wu, Baohui Han
Stem-like cells in solid tumors are purported to contribute to cancer development and poor treatment outcome. The abilities to self-renew, differentiate, and resist anticancer therapies are hallmarks of these rare cells, and steering them into lineage commitment may be one strategy to curb cancer development or progression. Vitamin D is a prohormone that can alter cell growth and differentiation and may induce the differentiation cancer stem-like cells. In this study, octamer-binding transcription factor 4 (OCT4)-positive/Nanog homeobox (Nanog)- positive lung adenocarcinoma stem-like cells (LACSCs) were enriched from spheroid cultured SPC-A1 cells and differentiated by a two-stage induction (TSI) method, which involved knockdown of hypoxia-inducible factor 1-alpha (HIF1α) expression (first stage) followed by sequential induction with 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3, VD3) and suberoylanilide hydroxamic acid (SAHA) treatment (second stage)...
August 31, 2016: Oncotarget
J P Mansell, M Cooke, M Read, H Rudd, A I Shiel, K Wilkins, M Manso
Chitinase 3-like 1, otherwise known as YKL-40, is a secreted glycoprotein purported to have a role in extracellular matrix metabolism. The first mammalian cell type found to express YKL-40 was the human osteosarcoma-derived osteoblast, MG63. In that first study the active vitamin D3 metabolite, 1,25-dihydroxycholecalciferol (1,25D), stimulated YKL-40 expression, thereby indicating that a vital factor for skeletal health promoted YKL-40 synthesis by bone forming cells. However, when these MG63 cells were exposed to 1,25D they were also exposed to serum, a rich source of the pleiotropic lipid mediator, lysophosphatidic acid (LPA)...
September 2016: Biochimie
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