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https://www.readbyqxmd.com/read/29344330/developments-in-rare-bone-diseases-and-mineral-disorders
#1
REVIEW
Siobhan Bacon, Rachel Crowley
In the last decade, there have been a number of significant advances made in the field of rare bone diseases. In this review, we discuss the expansion of the classification system for osteogenesis imperfecta (OI) and the resultant increase in therapeutic options available for management of OI. Bisphosphonates remain the most widely used intervention for OI, although the effect on fracture rate reduction is equivocal. We review the other therapies showing promising results, including denosumab, teriparatide, sclerostin, transforming growth factor β inhibition and gene targeted approaches...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29338760/increased-plasmodium-chabaudi-malaria-mortality-in-mice-with-nutritional-iron-deficiency-can-be-reduced-by-short-term-adjunctive-iron-supplementation
#2
Filip C Castberg, Lasse Maretty, Trine Staalsoe, Casper Hempel, Erik Clasen-Linde, Lars Hviid, Jørgen A L Kurtzhals
BACKGROUND: Iron deficiency is the most widespread nutrient deficiency and an important cause of developmental impairment in children. However, some studies have indicated that iron deficiency can also protect against malaria, which is a leading cause of childhood morbidity and mortality in large parts of the world. This has rendered interventions against iron deficiency in malaria-endemic areas controversial. METHODS: The effect of nutritional iron deficiency on the clinical outcome of Plasmodium chabaudi AS infection in A/J mice and the impact of intravenous iron supplementation with ferric carboxymaltose were studied before and after parasite infection...
January 16, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29337188/abrogation-of-fam20c-altered-cell-behaviors-and-bmp-signaling-of-immortalized-dental-mesenchymal-cells
#3
Chao Liu, Nan Zhou, Yu Wang, Hua Zhang, Priyam Jani, Xiaofang Wang, Yongbo Lu, Nan Li, Jing Xiao, Chunlin Qin
FAM20C mutations compromise the mineralization of skeleton and tooth in both human and mouse. Putatively, the mineralization disorder is attributed to the elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus by suppressing the reabsorption of phosphorus in kidney. Besides the regulation on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell behaviors and gene expression through a cell-autonomous manner. To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus...
January 11, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29336609/fibroblast-growth-factor-23-fgf23-gene-polymorphisms-are-associated-with-essential-hypertension-risk-and-blood-pressure-levels-in-chinese-han-population
#4
Peng Cai, Yan Peng, Li Li, Wei Chu, Xukai Wang
In this case-control study, 246 EH patients and 157 healthy controls were selected from Chinese Han population to explore the associations between the fibroblast growth factor 23 (FGF23) gene polymorphisms and essential hypertension (EH).The SequenomMassarray system was used for the genotyping of three FGF23 gene Tag single-nucleotide polymorphisms, namely rs7955866, rs13312756, and rs3812822. The primers were designed by Assay Designer 3.1 software, and then the samples were added to a 384-well plate for the polymerase chain reaction amplification, shrimp alkaline phosphatase reaction, and desalting after extension...
January 16, 2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29334610/phase-ii-study-of-dovitinib-in-patients-with-castration-resistant-prostate-cancer-kcsg-gu11-05
#5
Yoon Ji Choi, Hye Sook Kim, Se Hoon Park, Bong-Seog Kim, Kyoung Ha Kim, Hyo Jin Lee, Hong Suk Song, Dong-Yeop Shin, Ha Young Lee, Hoon-Gu Kim, Kyung Hee Lee, Jae Lyun Lee, Kyong Hwa Park
Purpose: Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC). Materials and Methods: This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500mg/day (5-days-on/2-days-off schedule)...
January 2, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29325796/lcz696-sacubitril-valsartan-an-angiotensin-receptor-neprilysin-inhibitor-attenuates-cardiac-hypertrophy-fibrosis-and-vasculopathy-in-a-rat-model-of-chronic-kidney-disease
#6
Yasunori Suematsu, Wanghui Jing, Ane Nunes, Moti L Kashyap, Mahyar Khazaeli, Nosratola D Vaziri, Hamid Moradi
BACKGROUND: Chronic kidney disease (CKD) is associated with cardiac hypertrophy, fibrosis and increased risk of cardiovascular mortality. LCZ696 (Sacubitril/valsartan) is a promising agent which has shown significant potential in treatment of heart failure. We hypothesized that LCZ696 is more effective than valsartan alone in treatment of cardiovascular abnormalities associated with experimental CKD. METHODS AND RESULTS: Male Sprague Dawley rats underwent 5/6 nephrectomy and were subsequently randomized to no treatment (CKD), 30 mg/kg valsartan (VAL), or 60 mg/kg LCZ696 (LCZ)...
January 8, 2018: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/29317227/prolonged-exposure-to-1-25-oh-2d3-and-high-ionized-calcium-induces-fgf-23-production-in-intestinal-epithelium-like-caco-2-monolayer-a-local-negative-feedback-for-preventing-excessive-calcium-transport
#7
Mayuree Rodrat, Kannikar Wongdee, Nattapon Panupinthu, Jirawan Thongbunchoo, Jarinthorn Teerapornpuntakit, Nateetip Krishnamra, Narattaphol Charoenphandhu
Overdose of oral calcium supplement and excessive intestinal calcium absorption can contribute pathophysiological conditions, e.g., nephrolithiasis, vascular calcification, dementia, and cardiovascular accident. Since our previous investigation has indicated that fibroblast growth factor (FGF)-23 could abolish the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-enhanced calcium absorption, we further hypothesized that FGF-23 produced locally in the enterocytes might be part of a local negative feedback loop to regulate calcium absorption...
January 6, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29311711/association-of-bap-with-urinary-albumin-excretion-in-postmenopausal-but-not-premenopausal-non-ckd-japanese-women
#8
Etsuko Ozaki, Shinsuke Yamada, Nagato Kuriyama, Daisuke Matsui, Isao Watanabe, Teruhide Koyama, Yasuo Imanishi, Masaaki Inaba, Yoshiyuki Watanabe
We investigated whether the phosphate (Pi) load in the circulation causes renal damage in non-CKD women. This cross-sectional study included 1,094 non-CKD Japanese women. Fibroblast growth factor (FGF)-23 as a parameter for the Pi load, bone alkaline phosphatase (BAP) as a bone metabolic marker, and the urinary albumin-to-creatinine ratio (UACR) as an early marker for renal damage were measured. Postmenopausal women exhibited significantly higher levels of serum Pi, FGF-23, BAP, and UACR and significantly lower eGFR than premenopausal women...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29306478/fibroblast-growth-factor-23-is-related-to-profiles-indicating-volume-overload-poor-therapy-optimization-and-prognosis-in-patients-with-new-onset-and-worsening-heart-failure
#9
Jozine M Ter Maaten, Adriaan A Voors, Kevin Damman, Peter van der Meer, Stefan D Anker, John G Cleland, Kenneth Dickstein, Gerasimos Filippatos, Pim van der Harst, Hans L Hillege, Chim C Lang, Marco Metra, Gerjan Navis, Leong Ng, Wouter Ouwerkerk, Piotr Ponikowski, Nilesh J Samani, Dirk J van Veldhuisen, Faiez Zannad, Aeilko H Zwinderman, Martin H de Borst
BACKGROUND: Fibroblast growth factor (FGF) 23 is a hormone that increases urinary phosphate excretion and regulates renal sodium reabsorption and plasma volume. We studied the role of plasma FGF23 in therapy optimization and outcomes in patients with new-onset and worsening heart failure (HF). METHODS: We measured plasma C-terminal FGF23 levels at baseline in 2399 of the 2516 patients included in the BIOlogy Study to Tailored Treatment in Chronic HF (BIOSTAT-CHF) trial...
February 15, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29304245/circulating-adiponectin-modifies-the-fgf23-response-to-vitamin-d-receptor-activation-a-post-hoc-analysis-of-a-double-blind-randomized-clinical-trial
#10
Belinda Spoto, Patrizia Pizzini, Giovanni Tripepi, Francesca Mallamaci, Carmine Zoccali
Background: The fibroblast growth factor 23 (FGF23) response to phosphate load is suppressed in adiponectin gene null mice and substantially amplified in mice overexpressing the same gene and vitamin D receptor (VDR) activation markedly enhances FGF23 gene expression. Methods: We performed an analysis of the static (baseline adiponectin levels) and dynamic (fluctuations in adiponectin levels) interactions of serum adiponectin with the FGF23 response to paricalcitol and placebo in the setting of a double-blind, randomized clinical trial in chronic kidney disease (CKD) patients (NCT01680198)...
February 3, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29301137/associations-of-fibroblast-growth-factor-23-with-markers-of-inflammation-and-leukocyte-transmigration-in-chronic-kidney-disease
#11
Carin Wallquist, Ladan Mansouri, Mattias Norrbäck, Britta Hylander, Stefan H Jacobson, Tobias E Larsson, Joachim Lundahl
BACKGROUND: Patients with chronic kidney disease (CKD) show elevated levels of inflammatory markers and have an increased risk of infections as well as cardiovascular morbidity. Recent studies have implied effects of fibroblast growth factor 23 (FGF23) on inflammation in CKD. We analyzed potential correlations between levels of FGF23 with pro-inflammatory chemokines and markers of leukocyte transmigration in CKD patients. METHODS: One hundred three patients with CKD 2-5ND and 54 healthy controls, had biochemical markers in blood and urine analyzed according to routine protocol...
January 4, 2018: Nephron
https://www.readbyqxmd.com/read/29298794/severe-fgf23-based-hypophosphataemic-osteomalacia-due-to-ferric-carboxymaltose-administration
#12
Klara Klein, Shonda Asaad, Michael Econs, Janet E Rubin
Ferric carboxymaltose (FCM) is a novel iron formulation increasingly prescribed due to its effectiveness and fast infusion time. FCM administration can cause an asymptomatic hypophosphataemia secondary to fibroblast growth factor 23 (FGF23) dysregulation. In patients with chronic iron needs, however, a severe, long-lasting hypophosphataemia can lead to osteomalacia with associated bone pain. Lack of awareness of this complication results in delayed time to diagnosis and significant morbidity. We report a case of a patient with Crohn's disease and chronic iron-deficiency anaemia receiving multiple doses of FCM who developed severe hypophosphataemic osteomalacia with urinary phosphate loss and increased FGF23...
January 3, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29284239/the-potential-impact-of-the-hypovitaminosis-d-on-metabolic-complications-in-obese-adolescents-preliminary-results
#13
Malgorzata Wojcik, Dominika Janus, Anna Kalicka-Kasperczyk, Krystyna Sztefko, Jerzy B Starzyk
INTRODUCTION AND OBJECTIVE: Vitamin D deficiency is common in obesity; however, its contribution in the development of metabolic complications remains uncertain. The aim of the study was to examine the relationships between vitamin D status and metabolic complications. MATERIAL AND METHODS: The results of blood pressure measurements, biochemical tests and ultrasound of the liver were compared in both groups. The study was conducted at the Children's University Hospital in Krakow, Poland...
December 23, 2017: Annals of Agricultural and Environmental Medicine: AAEM
https://www.readbyqxmd.com/read/29281993/vitamin-e-protects-against-extraskeletal-calcification-in-uremic-rats-fed-high-fat-diets
#14
Rafael Rios, Ana I Raya, Carmen Pineda, Mariano Rodriguez, Ignacio Lopez, Escolastico Aguilera-Tejero
BACKGROUND: High fat diets are implicated in the pathogenesis of metabolic syndrome, obesity and renal disease. Previous studies have revealed that high fat diets promote vascular calcification in uremic rats. Moreover, vitamin E has been shown to prevent uremic calcifications in genetically obese Zucker rats fed standard diet. The objective of this study was to investigate the influence of vitamin E supplementation on the development of extraskeletal calcifications in non-obese (wild type) uremic rats fed high fat diets...
December 28, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/29279421/-bone-derived-hormones-and-their-systemic-regulation
#15
Yuichi Takashi, Seiji Fukumoto, Toshio Matsumoto
Bone has several functions such as supporting our body, protecting internal organs and contributing to hematopoiesis. Recently, it has been revealed that bone also works as an endocrine tissue and systemically regulates functions of other organs. It has been reported that fibroblast growth factor 23(FGF23)regulates phosphate metabolism and osteocalcin affect glucose/energy metabolism. In addition, sclerostin, interleukin-11(IL-11)and lipocalin 2 have been also found to be bone-derived humoral factors. Further investigation concerning the network systems among multiple organs via bone-derived hormones may lead to the development of new drugs...
2018: Clinical Calcium
https://www.readbyqxmd.com/read/29259745/identification-of-an-indazole-based-pharmacophore-for-the-inhibition-of-fgfr-kinases-using-fragment-led-de-novo-design
#16
Lewis D Turner, Abbey J Summers, Laura O Johnson, Margaret A Knowles, Colin W G Fishwick
Structure-based drug design (SBDD) has become a powerful tool utilized by medicinal chemists to rationally guide the drug discovery process. Herein, we describe the use of SPROUT, a de novo-based program, to identify an indazole-based pharmacophore for the inhibition of fibroblast growth factor receptor (FGFR) kinases, which are validated targets for cancer therapy. Hit identification using SPROUT yielded 6-phenylindole as a small fragment predicted to bind to FGFR1. With the aid of docking models, several modifications to the indole were made to optimize the fragment to an indazole-containing pharmacophore, leading to a library of compounds containing 23 derivatives...
December 14, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29244678/oncogenic-osteomalacia-secondary-to-a-metastatic-phosphaturic-mesenchymal-tumor-in-the-talus-a-case-report-and-review-of-the-literature
#17
Keith T Aziz, Edward F McCarthy, Carol D Morris
CASE: We report the case of a 50-year-old woman with oncogenic osteomalacia secondary to a metastatic phosphaturic mesenchymal tumor (PMT) that presented, to our knowledge, with the first reported lesion in the talus. CONCLUSION: Oncogenic osteomalacia is a rare condition with a unique serum biochemical profile that requires a high index of suspicion for diagnosis. A PMT is a rare neoplasm that can lead to oncogenic osteomalacia through secretion of fibroblast growth factor 23...
April 2017: JBJS Case Connector
https://www.readbyqxmd.com/read/29228885/multiplex-analysis-of-serum-hormone-and-cytokine-in-patients-with-cervical-copll-towards-understanding-the-potential-pathogenic-mechanisms
#18
Guo-Dong Cai, Zhuang-Chen Zhu, Jun-Qin Wang, Guang Chen, Zeng Wang, Chen-Song Yang, Gui-Xin Sun
Cervical ossification of the posterior longitudinal ligament (cOPLL) is one of the major causes of myelopathy. However, the mechanism underlying remains elusive. In the present study, using MILLIPLEX magnetic bead panel, we investigated four serum hormones and six serum cytokines in cOPLL patients and healthy subjects. The results showed that tumor necrosis factore-α (TNF-α) were significantly increased, and DDK-1 was significantly decreased in the serum from male and female cOPLL patients compared with those from healthy controls, respectively...
October 2017: Growth Factors
https://www.readbyqxmd.com/read/29223639/extensive-phenotyping-of-the-orofacial-and-dental-complex-in-crouzon-syndrome
#19
Alexander Khominsky, Robin Yong, Sarbin Ranjitkar, Grant Townsend, Peter J Anderson
OBJECTIVES: Fibroblast growth factor receptor 2 (FGFR2) C342Y/+ mutation is a known cause of Crouzon syndrome that is characterised by craniosynostosis and midfacial hypoplasia. Our aim was to conduct extensive phenotyping of the maxillary, mandibular and dental morphology associated with this mutation. MATERIALS AND METHODS: Morphometric data were obtained from 40 mice, representing two genotypes (Crouzon and wild-type) and two sexes (males and females) (n=10 in each group)...
October 27, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/29208626/the-effect-of-extended-release-niacin-on-markers-of-mineral-metabolism-in-ckd
#20
Rakesh Malhotra, Ronit Katz, Andrew Hoofnagle, Andrew Bostom, Dena E Rifkin, Ruth Mcbride, Jeffrey Probstfield, Geoffrey Block, Joachim H Ix
BACKGROUND AND OBJECTIVES: Niacin downregulates intestinal sodium-dependent phosphate transporter 2b expression and reduces intestinal phosphate transport. Short-term studies have suggested that niacin lowers serum phosphate concentrations in patients with CKD and ESRD. However, the long-term effects of niacin on serum phosphate and other mineral markers are unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Trial was a randomized, double-blind, placebo-controlled trial testing extended release niacin in persons with prevalent cardiovascular disease...
January 6, 2018: Clinical Journal of the American Society of Nephrology: CJASN
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