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Paricalcitol

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https://www.readbyqxmd.com/read/28547797/vitamin-d-receptor-agonists-regulate-ocular-developmental-angiogenesis-and-modulate-expression-of-dre-mir-21-and-vegf
#1
Stephanie L Merrigan, Breandán N Kennedy
BACKGROUND AND PURPOSE: Pathological growth of ocular vasculature networks can underpin visual impairment in neovascular age-related macular degeneration, proliferative diabetic retinopathy and retinopathy of prematurity. Our aim was to uncover novel pharmacological regulators of ocular angiogenesis by phenotype-based screening in zebrafish. EXPERIMENTAL APPROACH: A bioactive chemical library of 465 drugs was screened to identify small molecule inhibitors of ocular hyaloid vasculature (HV) angiogenesis in zebrafish larvae...
May 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28511692/vitamin-d-receptor-activation-reduces-inflammatory-cytokines-and-plasma-micrornas-in-moderate-chronic-kidney-disease-a-randomized-trial
#2
Ladan Mansouri, Kristina Lundwall, Ali Moshfegh, Stefan H Jacobson, Joachim Lundahl, Jonas Spaak
BACKGROUND: Chronic kidney disease (CKD) is a major risk factor for cardiovascular disease (CVD), partly due to endothelial dysfunction and chronic inflammation. Vitamin D treatment in end stage renal disease is suggested to modulate the immune system and lead to improved outcomes. We and others have demonstrated that treatment with vitamin D or activated vitamin D analogues protects the endothelial function in less severe renal disease as well. Since the endothelial protection might be mediated by vitamin D effects on inflammation, we assessed levels of pro-inflammatory cytokines and micro RNAs (miRs) in patients with moderate CKD, treated with an active vitamin D analogue (paricalcitol)...
May 16, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28465762/paricalcitol-pretreatment-attenuates-renal-ischemia-reperfusion-injury-via-prostaglandin-e2-receptor-ep4-pathway
#3
Yu Ah Hong, Keum Jin Yang, So Young Jung, Ki Cheol Park, Hyunsu Choi, Jeong Min Oh, Sang Ju Lee, Yoon Kyung Chang, Cheol Whee Park, Chul Woo Yang, Suk Young Kim, Hyeon Seok Hwang
The protective mechanism of paricalcitol remains unclear in renal ischemia-reperfusion (IR) injury. We investigated the renoprotective effects of paricalcitol in IR injury through the prostaglandin E2 (PGE2) receptor EP4. Paricalcitol was injected into IR-exposed HK-2 cells and mice subjected to bilateral kidney ischemia for 23 min and reperfusion for 24 hr. Paricalcitol prevented IR-induced cell death and EP4 antagonist cotreatment offset these protective effects. Paricalcitol increased phosphorylation of Akt and cyclic AMP responsive element binding protein (CREB) and suppressed nuclear factor-κB (NF-κB) in IR-exposed cells and cotreatment of EP4 antagonist or EP4 small interfering RNA blunted these signals...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28460073/regulation-of-mir-29b-and-mir-30c-by-vitamin-d-receptor-activators-contributes-to-attenuate-uraemia-induced-cardiac-fibrosis
#4
Sara Panizo, Natalia Carrillo-López, Manuel Naves-Díaz, Guillermo Solache-Berrocal, Laura Martínez-Arias, Raúl R Rodrigues-Díez, Amalia Fernández-Vázquez, Carlos Martínez-Salgado, Marta Ruiz-Ortega, Adriana Dusso, Jorge B Cannata-Andía, Isabel Rodríguez
Background.: Uraemic cardiomyopathy, a process mainly associated with increased myocardial fibrosis, is the leading cause of death in chronic kidney disease patients and can be prevented by vitamin D receptor activators (VDRAs). Since some microRNAs (miRNAs) have emerged as regulators of the fibrotic process, we aimed to analyse the role of specific miRNAs in VDRA prevention of myocardial fibrosis as well as their potential use as biomarkers. Methods.: Wistar rats were nephrectomized and treated intraperitoneally with equivalent doses of two VDRAs: calcitriol and paricalcitol...
April 28, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28451892/oral-paricalcitol-expanding-therapeutic-options-for-pediatric-chronic-kidney-disease-patients
#5
EDITORIAL
Michael Freundlich, Carolyn L Abitbol
The complex pathophysiology of progressive chronic kidney disease (CKD) and the development of mineral and bone disorder, abbreviated as CKD-MBD, is of vital importance to a pediatric patient. Paricalcitol, the 19 nor-1,25(OH)2D2 analogue was shown to be effective and safe in the treatment of secondary hyperparathyroidism (SHPT) in adults almost two decades ago. It also significantly improved survival in dialysis patients compared to the standard calcitriol. The successful treatment of CKD-MBD in children is essential if they are to grow and survive into adulthood...
April 27, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28442557/high-phosphate-induces-a-pro-inflammatory-response-by-vascular-smooth-muscle-cells-modulation-by-vitamin-d-derivatives
#6
Julio M Martínez-Moreno, Carmen Herencia, Addy Montes de Oca, Juan M Díaz-Tocados, Noemi Vergara, Mª José Gomez, Silvia D López-Argüello, Antonio Camargo, Esther Peralbo-Santaella, Maria E Rodríguez-Ortiz, Antonio Canalejo, Mariano Rodriguez, Juan R Muñoz-Castañeda, Yolanda Almaden
In chronic kidney disease patients, high phosphate (HP) levels are associated to cardiovascular disease, the major cause of morbidity and mortality. Since serum phosphate has been independently correlated with inflammation, the present study aimed to investigate an independent direct effect of HP as a pro-inflammatory factor in VSMCs. A possible modulatory effect of vitamin D was also investigated. The study was performed in an in vitro model of human aortic smooth muscle cells (HASMCs). Incubation of cells in a HP (3...
April 25, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28436117/early-introduction-of-oral-paricalcitol-in-renal-transplant-recipients-an-open-label-randomized-study
#7
Hege Kampen Pihlstrøm, Franscesca Gatti, Clara Hammarström, Ivar Anders Eide, Monika Kasprzycka, Junbai Wang, Guttorm Haraldsen, My Hanna Sofia Svensson, Karsten Midtvedt, Geir Mjøen, Dag Olav Dahle, Anders Hartmann, Hallvard Holdaas
In stable renal transplant recipients with hyperparathyroidism, previous studies have indicated that vitamin D agonist treatment might have anti-proteinuric effects. Animal studies indicate possible anti-fibrotic and anti-inflammatory effects. Early introduction of paricalcitol in de-novo renal transplant recipients might reduce proteinuria and prevent progressive allograft fibrosis. We performed a single-centre, prospective, randomized, open-label trial investigating effects of paricalcitol 2μg/day added to standard care...
April 24, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28423536/jmjd3-suppresses-stem-cell-like-characteristics-in-breast-cancer-cells-by-downregulation-of-oct4-independently-of-its-demethylase-activity
#8
Jing Xun, Dekun Wang, Long Shen, Junbo Gong, Ruifang Gao, Lingfang Du, Antao Chang, Xiangrong Song, Rong Xiang, Xiaoyue Tan
Epigenetic regulator JMJD3 plays an important role in both tumor progression and somatic cell reprogramming. Here, we explored the effect of JMJD3 on the stem cell-like characteristics of breast cancer and its underlying mechanism involving stemness-related transcription factor Oct4. Our data revealed that, in breast cancer cells lines and an orthotopic xenograph mouse model of breast cancer, ectopic overexpression of JMJD3 suppressed stem cell-like characteristics of breast cancer cells, whereas knockdown of JMJD3 promoted these characteristics...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28380670/improved-regeneration-and-de-novo-bone-formation-in-a-diabetic-zebrafish-model-treated-with-paricalcitol-and-cinacalcet
#9
Filipe R Carvalho, Ana R Fernandes, M Leonor Cancela, Paulo J Gavaia
Bone changes related to diabetes have been well stablished, but few strategies have been developed to prevent this growing health problem. In our work, we propose to investigate the effects of calcitriol as well as of a vitamin D analog (paricalcitol) and a calcimimetic (cinacalcet), in fin regeneration and de novo mineralization in a zebrafish model of diabetes. Following exposure of diabetic transgenic Tg(ins:nfsb-mCherry) zebrafish to calcitriol, paricalcitol and cinacalcet, caudal fins were amputated to assess their effects on tissue regeneration...
April 5, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28332096/efficacy-and-safety-of-paricalcitol-in-children-with-stages-3-to-5-chronic-kidney-disease
#10
Nicholas J A Webb, Gary Lerner, Bradley A Warady, Katherine M Dell, Larry A Greenbaum, Gema Ariceta, Bernd Hoppe, Peter Linde, Ho-Jin Lee, Ann Eldred, Matthew B Dufek
BACKGROUND: Elevated intact parathyroid hormone (iPTH) levels can contribute to morbidity and mortality in children with chronic kidney disease (CKD). We evaluated the pharmacokinetics, efficacy, and safety of oral paricalcitol in reducing iPTH levels in children with stages 3-5 CKD. METHODS: Children aged 10-16 years with stages 3-5 CKD were enrolled in two phase 3 studies. The stage 3/4 CKD study characterized paricalcitol pharmacokinetics and compared the efficacy and safety of paricalcitol with placebo followed by an open-label period...
March 22, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28325259/vitamin-d-analogues-potential-use-in-cancer-treatment
#11
REVIEW
Michael J Duffy, Alyson Murray, Naoise C Synnott, Norma O'Donovan, John Crown
The vitamin D receptor (VDR) is a member of the thyroid-steroid family of nuclear transcription factors. Following binding of the active form of vitamin D, i.e., 1,25(OH)2D3 (also known as calcitriol) and interaction with co-activators and co-repressors, VDR regulates the expression of several different genes. Although relatively little work has been carried out on VDR in human cancers, several epidemiological studies suggest that low circulating levels of vitamin D are associated with both an increased risk of developing specific cancer types and poor outcome in patients with specific diagnosed cancers...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28303937/vitamin-d-inhibits-lymphangiogenesis-through-vdr-dependent-mechanisms
#12
Saleh Yazdani, Fariba Poosti, Luis Toro, Johannes Wedel, Rik Mencke, Katarina Mirković, Martin H de Borst, J Steven Alexander, Gerjan Navis, Harry van Goor, Jacob van den Born, Jan-Luuk Hillebrands
Excessive lymphangiogenesis is associated with cancer progression and renal disease. Attenuation of lymphangiogenesis might represent a novel strategy to target disease progression although clinically approved anti-lymphangiogenic drugs are not available yet. VitaminD(VitD)-deficiency is associated with increased cancer risk and chronic kidney disease. Presently, effects of VitD on lymphangiogenesis are unknown. Given the apparently protective effects of VitD and the deleterious associations of lymphangiogenesis with renal disease, we here tested the hypothesis that VitD has direct anti-lymphangiogenic effects in vitro and is able to attenuate lymphangiogenesis in vivo...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261302/the-vitamin-d-analogue-paricalcitol-attenuates-hepatic-ischemia-reperfusion-injury-through-down-regulation-of-toll-like-receptor-4-signaling-in-rats
#13
Min Sung Kim, Soyoung Lee, Namhee Jung, Kiho Lee, Jinwoo Choi, Sang-Hoon Kim, Jinhyun Jun, Won-Mee Lee, Yeonsoo Chang, Donghee Kim
INTRODUCTION: Recent studies have revealed that vitamin D and its synthetic analogues have a protective effect on experimental ischemia/reperfusion (I/R) models in several organs, but little is known about its effect on the liver. The aim of this study was to evaluate the beneficial effects of vitamin D in a model of liver I/R in rats, focusing on Toll-like receptor (TLR) 4 signaling, which has been shown to be involved in I/R injury. MATERIAL AND METHODS: Twenty-four male Wistar rats were randomized into four groups: Saline + Sham, Saline + I/R, Paricalcitol + Sham, and Paricalcitol + I/R...
March 1, 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28073343/risk-factors-and-clinical-course-of-hungry-bone-syndrome-after-total-parathyroidectomy-in-dialysis-patients-with-secondary-hyperparathyroidism
#14
Lo-Yi Ho, Ping-Nam Wong, Ho-Kwan Sin, Yuk-Yi Wong, Kwok-Chi Lo, Shuk-Fan Chan, Man-Wai Lo, Kin-Yee Lo, Siu-Ka Mak, Andrew Kui-Man Wong
BACKGROUND: Hungry bone syndrome (HBS) is an important postoperative complication after parathyroidectomy for severe secondary hyperparathyroidism (SHPT). There is, however, little data in the literature on its detailed clinical course, and the associated risk factors remain controversial. METHODS: We did a single-center retrospective study on 62 consecutive dialysis patients who underwent total parathyroidectomy for SHPT to examine the risk factors, clinical course and outcome...
January 10, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28017524/active-vitamin-d-treatment-in-ckd-patients-raises-serum-sclerostin-and-this-effect-is-modified-by-circulating-pentosidine-levels
#15
C Torino, P Pizzini, S Cutrupi, G Tripepi, F Mallamaci, R Thadhani, C Zoccali
BACKGROUND AND AIMS: 1,25(OH)2Vitamin D increases the expression of the sclerostin gene. Whether vitamin D receptor activation (VDRA) influences serum sclerostin in CKD and whether compounds interfering with VDRA like Advanced Glycosylation End Products (AGEs) may alter the sclerostin response to VDRA is unknown. METHODS AND RESULTS: Eighty-eight stage G3-4 CKD patients randomly received 2 μg paricalcitol (PCT)/day (n = 44) or placebo (n = 44) for 12 weeks...
November 23, 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28002889/variability-in-response-to-albuminuria-lowering-drugs-true-or-random
#16
Sergei I Petrykiv, Dick de Zeeuw, Frederik Persson, Peter Rossing, Ron T Gansevoort, Gozewijn D Laverman, Hiddo J L Heerspink
AIMS: Albuminuria-lowering drugs have shown different effect size in different individuals. Since urine albumin levels are known to vary considerably from day-to-day, we questioned whether the between-individual variability in albuminuria response after therapy initiation reflects a random variability or a true response variation to treatment. In addition, we questioned whether the response variability is drug dependent. METHODS: To determine whether the response to treatment is random or a true drug response, we correlated in six clinical trials the change in albuminuria during placebo or active treatment (on-treatment) with the change in albuminuria during wash-out (off-treatment)...
June 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27989797/vitamin-d-receptor-agonist-vs-105-directly-modulates-parathyroid-hormone-expression-in-human-parathyroid-cells-and-in-5-6-nephrectomized-rats
#17
Kaichiro Sawada, J Ruth Wu-Wong, Yung-Wu Chen, Jerry L Wessale, Genta Kanai, Takatoshi Kakuta, Masafumi Fukagawa
Vitamin D receptor (VDR) agonists (VDRAs) are commonly used to treat secondary hyperparathyroidism (SHPT) associated with chronic kidney disease (CKD). Current VDRA therapy often causes hypercalcemia, which is a critical risk for vascular calcification. Previously we have shown that a novel VDRA, VS-105, effectively suppresses serum parathyroid hormone (PTH) without affecting serum calcium levels in 5/6 nephrectomized (NX) uremic rats. However, it is not known whether VS-105 directly regulates PTH gene expression...
March 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27856633/effects-of-vitamin-d-receptor-activation-and-dietary-sodium-restriction-on-residual-albuminuria-in-ckd-the-virtue-ckd-trial
#18
RANDOMIZED CONTROLLED TRIAL
Charlotte A Keyzer, G Fenna van Breda, Marc G Vervloet, Maarten A de Jong, Gozewijn D Laverman, Marc H Hemmelder, Wilbert M T Janssen, Hiddo J Lambers Heerspink, Arjan J Kwakernaak, Stephan J L Bakker, Gerjan Navis, Martin H de Borst
Reduction of residual albuminuria during single-agent renin-angiotensin-aldosterone blockade is accompanied by improved cardiorenal outcomes in CKD. We studied the individual and combined effects of the vitamin D receptor activator paricalcitol (PARI) and dietary sodium restriction on residual albuminuria in CKD. In a multicenter, randomized, placebo (PLAC)-controlled, crossover trial, 45 patients with nondiabetic CKD stages 1-3 and albuminuria >300 mg/24 h despite ramipril at 10 mg/d and BP<140/90 mmHg were treated for four 8-week periods with PARI (2 μg/d) or PLAC, each combined with a low-sodium (LS) or regular sodium (RS) diet...
April 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27827962/cholecalciferol-additively-reduces-serum-parathyroid-hormone-and-increases-vitamin-d-and-cathelicidin-levels-in-paricalcitol-treated-secondary-hyperparathyroid-hemodialysis-patients
#19
RANDOMIZED CONTROLLED TRIAL
Jing-Quan Zheng, Yi-Chou Hou, Cai-Mei Zheng, Chien-Lin Lu, Wen-Chih Liu, Chia-Chao Wu, Ming-Te Huang, Yuh-Feng Lin, Kuo-Cheng Lu
BACKGROUND: Active Vitamin D analogues are used clinically for prevention and treatment of secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients. Nutritional vitamin D supplementation is used for additional local parathyroid (PTH) suppression, with lower incidence of hypercalcemia and hyperphosphatemia. This study evaluates the possible beneficial effects of combined vitamin D treatment (paricalcitol and cholecalciferol). METHODS: Sixty HD patients with serum parathyroid hormone (iPTH) >300 pg/mL were enrolled...
November 5, 2016: Nutrients
https://www.readbyqxmd.com/read/27818277/comparison-of-the-effects-of-novel-vitamin-d-receptor-analog-vs-105-and-paricalcitol-on-chronic-kidney-disease-mineral-bone-disorder-in-an-experimental-model-of-chronic-kidney-disease
#20
Hideki Fujii, Yuriko Yonekura, Kentaro Nakai, Keiji Kono, Shunsuke Goto, Shinichi Nishi
When using vitamin D, the most important clinical problems are hypercalcemia, hyperphosphatemia, and vascular calcification. VS-105 is a novel vitamin D receptor (VDR) analog. In the present study, we compared the effects of VS-105 and paricalcitol on chronic kidney disease-mineral bone disorder (CKD-MBD) in a CKD rat model. We used male Sprague-Dawley (SD) rats and performed 5/6 nephrectomy at 8-9 weeks. At 10 weeks, the rats were classified into five groups and administered vehicle, low-dose paricalcitol (LP, 0...
March 2017: Journal of Steroid Biochemistry and Molecular Biology
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