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https://www.readbyqxmd.com/read/28645356/-endocrine-control-of-serum-phosphate-from-the-discoveries-of-phosphatonins-to-novel-therapies
#1
A Linglart, C Chaussain
Phosphate is absorbed through the gut, stored in the bone and reabsorbed through the proximal renal tubule. More importantly, PTH and FGF23 have been identified as the main phosphaturic factors that control the expression of the phosphate co-transporters NaPi-IIa et IIc. By allowing the adjustment of the urinary phosphate reabsorption, these two phosphatonins play a major role in bone and tooth mineralization and growth. Recently, novel therapies have successfully targeted the FGF23 signaling pathway to treat the hypophosphatemia in patients affected with molecular defects of this pathway (mutations in the PHEX gene)...
October 2016: Annales D'endocrinologie
https://www.readbyqxmd.com/read/28630637/evaluation-of-circulating-srage-in-osteoporosis-according-to-bmi-adipokines-and-fracture-risk-a-pilot-observational-study
#2
Emanuela Galliera, Monica Gioia Marazzi, Carmine Gazzaruso, Pietro Gallotti, Adriana Coppola, Tiziana Montalcini, Arturo Pujia, Massimiliano M Corsi Romanelli
BACKGROUND: Osteoporosis is a systemic metabolic disease based on age-dependent imbalance between the rates of bone formation and bone resorption. Recent studies on the pathogenesis of this disease identified that bone remodelling impairment, at the base of osteoporotic bone fragility, could be related to protein glycation, in association to oxidative stress. The glycation reactions lead to the generation of glycation end products (AGEs) which, in turn, accumulates into bone, where they binds to the receptor for AGE (RAGE)...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28630081/calcium-sensing-receptor-genotype-and-response-to-cinacalcet-in-patients-undergoing-hemodialysis
#3
Sharon M Moe, Leah Wetherill, Brian Scott Decker, Dongbing Lai, Safa Abdalla, Jin Long, Matteo Vatta, Tatiana M Foroud, Glenn M Chertow
BACKGROUND AND OBJECTIVES: We tested the hypothesis that single nucleotide polymorphisms (SNPs) in the calcium-sensing receptor (CASR) alter the response to the calcimimetic cinacalcet. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed DNA samples in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial, a randomized trial comparing cinacalcet to placebo on a background of usual care. Of the 3883 patients randomized, 1919 (49%) consented to DNA collection, and samples from 1852 participants were genotyped for 18 CASR polymorphisms...
June 19, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28619026/elevated-serum-fibroblast-growth-factor-23-levels-as-an-indicator-of-lower-extremity-atherosclerotic-disease-in-chinese-patients-with-type-2-diabetes-mellitus
#4
Xingxing He, Xiang Hu, Xiaojing Ma, Hang Su, Lingwen Ying, Jiahui Peng, Xiaoping Pan, Yuqian Bao, Jian Zhou, Weiping Jia
BACKGROUND: Recently, basic and clinical studies have provided evidence supporting the relationship between circulating levels of fibroblast growth factor (FGF) 23 and the development of atherosclerosis. Given that diabetes is an established risk factor for lower extremity atherosclerotic disease (LEAD), the goal of the present study was to explore the relationship between serum FGF23 levels and LEAD, as well as the related factors, in Chinese patients with type 2 diabetes mellitus (T2DM)...
June 15, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28614212/phosphaturic-mesenchymal-tumors-clinicopathologic-immunohistochemical-and-molecular-analysis-of-22-cases-expanding-their-morphologic-and-immunophenotypic-spectrum
#5
Abbas Agaimy, Michael Michal, Simion Chiosea, Fredrik Petersson, Ladislav Hadravsky, Glenn Kristiansen, Raymund E Horch, Jan Schmolders, Arndt Hartmann, Florian Haller, Michal Michal
Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm of uncertain histogenesis that has been linked to tumor-induced osteomalacia (TIO) since 1959. The neoplastic cells produce increased amount of FGF23 which results in TIO via uncontrolled renal loss of phosphate (phosphaturia), and consequently diminished bone mineralization. To date, ∼300 cases have been reported. Although there is increasing evidence that PMT can be diagnosed by reproducible histopathologic features, firm diagnosis has been often restricted to cases associated with TIO and, hence, diagnosis of "nonphosphaturic variants" remained challenging...
June 13, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28614116/parathyroid-hormone-and-the-regulation-of-renal-tubular-calcium-transport
#6
Benjamin Ko
PURPOSE OF REVIEW: Renal tubule excretion of calcium is carefully and complexly regulated. At the center of this process, parathyroid hormone (PTH) is the chief regulator of renal calcium reabsorption. This review outlines our current understanding of PTH's effects on renal tubular calcium transport, focusing on the more recent discoveries beyond its direct regulation of epithelial Ca channel transient receptor potential vanilloid 5 (TRPV5) and looking at its interaction with sodium transport and the hormones fibroblast growth factor 23 (FGF23) and klotho...
June 12, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28611350/fgf23-is-synthesised-locally-by-renal-tubules-and-activates-injury-primed-fibroblasts
#7
Edward R Smith, Sven-Jean Tan, Stephen G Holt, Tim D Hewitson
In kidney disease, higher circulating levels of the mineral-regulating hormone fibroblast growth factor (FGF)-23 are predictive of disease progression but direct pathogenic effects on the kidney are unknown. We sought evidence of local renal synthesis in response to unilateral ureteric obstruction in the mouse, and pro-fibrotic actions of FGF23 on the fibroblast in vitro. Acute tubulointerstitial injury due to unilateral ureteric obstruction stimulated renal FGF23 synthesis by tubules, and downregulated inactivating proprotein convertases, without effects on systemic mineral metabolism...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28609833/pth-regulation-of-fgf23-fragments-a-tail-in-two-acts
#8
Larry J Suva, Peter A Friedman
No abstract text is available yet for this article.
April 29, 2017: Endocrinology
https://www.readbyqxmd.com/read/28600887/therapeutic-effects-of-fgf23-c-tail-fc-in-a-murine-pre-clinical-model-of-x-linked-hypophosphatemia-via-the-selective-modulation-of-phosphate-reabsorption
#9
Kristen Johnson, Kymberly Levine, Joseph Sergi, Jean Chamoun, Rachel Roach, Jackie Vekich, Mike Favis, Mark Horn, Xianjun Cao, Brian Miller, William Snyder, Dikran Aivazian, William Reagan, Edwin Berryman, Jennifer Colangelo, Victoria Markiewicz, Cedo Bagi, Thomas P Brown, Anthony Coyle, Moosa Mohammadi, Jeanne Magram
Fibroblast growth factor 23 (FGF23) is the causative factor of X-linked hypophosphatemia (XLH), a genetic disorder effecting 1:20,000 that is characterized by excessive phosphate excretion, elevated FGF23 levels and a rickets/osteomalacia phenotype. FGF23 inhibits phosphate reabsorption and suppresses 1α,25-dihydroxyvitamin D (1,25D) biosynthesis, analytes that differentially contribute to bone integrity and deleterious soft tissue mineralization. As inhibition of ligand broadly modulates downstream targets, balancing efficacy and unwanted toxicity is difficult when targeting the FGF23 pathway...
June 10, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28600880/klotho-lacks-a-fgf23-independent-role-in-mineral-homeostasis
#10
Olena Andrukhova, Jessica Bayer, Christiane Schüler, Ute Zeitz, Sathish K Murali, Sibel Ada, Jose M Alvarez-Pez, Alina Smorodchenko, Reinhold G Erben
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone regulating vitamin D hormone production and renal handling of minerals by signaling through a FGF receptor/αKlotho (Klotho) receptor complex. Whether Klotho has FGF23-independent effects on mineral homeostasis is a controversial issue. Here, we aimed to shed more light on this controversy by comparing male and female triple knockout mice with simultaneous deficiency in Fgf23 and Klotho and a nonfunctioning vitamin D receptor (VDR) (Fgf23/Klotho/VDR) with double (Fgf23/VDR, Klotho/VDR, and Fgf23/Klotho) and single Fgf23, Klotho and VDR mutants...
June 10, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28596573/fibroblast-growth-factor-23-weakens-chemotaxis-of-human-blood-neutrophils-in-microfluidic-devices
#11
Ke Yang, Hagit Peretz-Soroka, Jiandong Wu, Ling Zhu, Xueling Cui, Michael Zhang, Claudio Rigatto, Yong Liu, Francis Lin
Neutrophil trafficking in tissues critically regulates the body's immune response. Neutrophil migration can either play a protective role in host defense or cause health problems. Fibroblast growth factor 23 (FGF23) is a known biomarker for chronic kidney disease (CKD) and was recently shown to impair neutrophil arrest on endothelium and transendothelial migration. In the present study, we further examined the effect of FGF23 on human blood neutrophil chemotaxis using two new microfluidic devices. Our results showed that chemotaxis of FGF23 pre-treated neutrophils to a fMLP gradient, in the presence or absence of a uniform FGF23 background, is quantitatively lower compared to the control cells...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28594289/hypoxic-3d-cellular-network-construction-replicates-ex-vivo-the-phenotype-of-primary-human-osteocytes
#12
Saba Choudhary, Qiaoling Sun, Ciaran Mannion, Yair Kissin, Jenny Zilberberg, Woo Young Lee
Osteocytes are deeply embedded in the mineralized matrix of bone and are non-proliferative, making them a challenge to isolate and maintain using traditional in vitro culture methods without sacrificing their inimitable phenotype. We studied the synergistic effects of two microenvironmental factors that are vital in retaining, ex vivo, the phenotype of primary human osteocytes: hypoxia and 3D cellular network. In order to recapitulate the lacunocanalicular structure of bone tissue, we assembled and cultured primary human osteocytic cells with biphasic calcium phosphate microbeads in a microfluidic perfusion culture device...
June 8, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28585906/elevation-of-plasma-oncostatin-m-in-heart-failure
#13
Damien Gruson, Benjamin Ferracin, Sylvie A Ahn, Michel F Rousseau
AIM: Oncostatin M (OSM) is an inflammatory cytokine of the gp130 family. OSM could participate in adverse cardiovascular remodeling through regulation of FGF23. MATERIALS & METHODS: OSM levels were determined in 80 heart failure patients with reduced left ventricular ejection fraction (HFrEF). RESULTS: OSM levels are significantly increased in HFrEF patients compared with healthy subjects. We have also demonstrated that, in HFrEF patients, plasma OSM levels are correlated to parathyroid hormone PTH(1-84) and 1,25(OH)2D, two other biomarkers related to bone and mineral metabolism and associated to adverse cardiovascular outcomes...
June 6, 2017: Future Cardiology
https://www.readbyqxmd.com/read/28577750/-strategies-aiming-to-control-hyperphosphatemia-in-chronic-kidney-disease
#14
Pablo Antonio Ureña Torres
Chronic kidney disease is known to be associated with phosphate retention. The mechanisms are complex and the early increase in serum phosphate levels in chronic kidney disease is not strictly related to the dietary phosphate load or to the degree of phosphate retention. It also implicates the activity of intestinal sodium-phosphate cotransporters, the degree of bone turnover and the retention and/or phosphate release from the skeleton, and the feedback mechanisms regulating the phosphaturia. Indeed, the increase in serum phosphate levels is only a reflection of underlying complex mechanisms, and many important factors play a role including parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23), and others...
April 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28570402/genetic-factors-involved-in-mandibular-prognathism
#15
Anna Doraczynska-Kowalik, Kamil H Nelke, Wojciech Pawlak, Maria M Sasiadek, Hanna Gerber
Mandibular prognathism is defined as an abnormal forward projection of the mandible beyond the standard relation to the cranial base and it is usually categorized as both a skeletal Class III pattern and Angle Class III malocclusion. The etiology of mandibular prognathism is still uncertain, with various genetic, epigenetic, and environmental factors possibly involved. However, many reports on its coexistence in both twins and segregation in families suggest the importance of genetic influences. A multifactorial and polygenic background with a threshold for expression or an autosomal dominant mode with incomplete penetrance and variable expressivity are the most probable inheritance patterns...
May 31, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28558021/interactions-of-sclerostin-with-fgf23-soluble-klotho-and-vitamin-d-in-renal-transplantation
#16
Lida Tartaglione, Marzia Pasquali, Silverio Rotondi, Maria Luisa Muci, Cristiana Leonangeli, Alessio Farcomeni, Valeria Fassino, Sandro Mazzaferro
Relationships of Sclerostin, a bone anti-anabolic protein, with biomarkers of mineral bone disorders in chronic kidney disease are still unsettled, in particular in kidney transplant (KTR). In 80 KTR patients (31F/49M, 54.7±10.3 years) we studied the relationships of serum Sclerostin with eGFR, Calcium, Phosphate, Alkaline Phosphatase (AP), intact Parathyroid hormone (iPTH), soluble alpha-Klotho (sKlotho), intact Fibroblast Growth Factor 23 (iFGF23), 25-hydroxyvitamin D(25D) and 1,25-dihydroxyvitamin D (1,25D)...
2017: PloS One
https://www.readbyqxmd.com/read/28554171/clearance-of-sclerostin-osteocalcin-fibroblast-growth-factor-23-and-osteoprotegerin-by-dialysis
#17
Nicholas Carlson, Ole H Mortensen, Mette Axelsen, Robert S Pedersen, James G Heaf
INTRODUCTION: Fibroblast growth factor (FGF23), sclerostin, osteocalcin, and osteoprotegerin are important factors that control mineral bone metabolism. End-stage renal disease is associated with the pronounced dysregulation of mineral bone metabolism; however, the impact and clearance of mineral bone metabolism factors during dialysis remain largely undescribed. METHODS: In a cross-sectional study, 10 chronic hemodialysis patients were treated with hemodialysis for 8 h using a high-flux filter and a dialysate bath of 50% calculated total body water continuously recycled at a rate of 500 mL/min...
2017: Blood Purification
https://www.readbyqxmd.com/read/28543687/effect-of-a-single-intravenous-zoledronic-acid-administration-on-biomarkers-of-acute-kidney-injury-aki-in-patients-with-osteoporosis-a-pilot-study
#18
C Cipriani, J Pepe, C Clementelli, R Manai, L Colangelo, V Fassino, L Nieddu, S Minisola
AIMS: The pilot study was designed to evaluate the early effect of intravenous (iv) zoledronic acid (ZA) on renal function. METHODS: Five mg iv ZA was administered to 23 patients with osteoporosis (17 women and 6 men, mean age 73±7 SD years). Urinary NGAL, KIM-1, and MCP-1, plasma (p) MCP-1 and serum (s) IL-18, serum calcium (sCa), Creatinine clearance (CrCl), parathyroid hormone (PTH), plasma C-terminal FGF23 (pFGF23), serum (s) Klotho, calcium excretion (CaEx) and renal threshold phosphate concentration/GFR (TmPO4/GFR) were assessed at baseline, 24 hours (h) and day (d) 30 after administration...
May 25, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28535521/fibroblast-growth-factor-23-mineral-metabolism-and-beyond
#19
Alexander Grabner, Sandro Mazzaferro, Giuseppe Cianciolo, Stefanie Krick, Irene Capelli, Silverio Rotondi, Claudio Ronco, Gaetano La Manna, Christian Faul
Patients affected by chronic kidney disease (CKD) exhibit a high risk of cardiovascular mortality that is poorly explained by traditional risk factors. There is a growing awareness about the role of derangement of mineral metabolism that is currently accepted as a trigger and sustainer of cardiovascular disease (CVD) in CKD patients. The synthetic definition of CKD mineral and bone disorder (CKD-MBD) split the concept that the indexes of mineral metabolism extend their effects beyond the bone until the vascular wall and metabolic milieu of CKD patients through complex pathways...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28527242/-small-cell-lung-cancer-associated-with-multiple-paraneoplastic-syndromes
#20
Diana L Franco, Leslie Thomas
We report the case of a patient presenting with multiple severe electrolyte disturbances who was subsequently found to have small cell lung cancer. Upon further evaluation, she demonstrated three distinct paraneoplastic processes, including the syndrome of inappropriate antidiuretic hormone, Fanconi syndrome, and an inappropriate elevation in fibroblast growth factor-23 (FGF23). The patient underwent one round of chemotherapy, but she was found to have progressive disease. After 36 days of hospitalization, the patient made the decision to enter hospice care and later she expired...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
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