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Monica Jain, David L Krasne, Frederick R Singer, Armando E Giuliano
Parathyromatosis is a rare condition consisting of multiple nodules of benign hyperfunctioning parathyroid tissue scattered throughout the neck and superior mediastinum. As a potential cause of recurrent or persistent hyperparathyroidism, parathyromatosis is a challenging condition to diagnose and treat. The optimal evaluation and management of patients with parathyromatosis is not well established. The reported case involves a patient who was initially diagnosed with primary hyperparathyroidism. The diagnosis of Type 1 parathyromatosis was made after the patient developed recurrent hyperparathyroidism with hypercalcemia and osteoporosis 17 years after the initial operation and underwent two additional operations...
October 14, 2016: Endocrine
Alicja E Grzegorzewska, Mateusz Paciorkowski, Adrianna Mostowska, Bartosz Frycz, Wojciech Warchoł, Ireneusz Stolarek, Marek Figlerowicz, Paweł P Jagodziński
Nephrolithiasis, secondary hyperparathyroidism (sHPT), and cardiovascular complications are associated with disturbances in Ca handling and contribute to morbidity/mortality during haemodialysis (HD). Calcimimetics, activators of the calcium-sensing receptor (CaSR), provide an effective means of reducing parathyroid hormone (PTH) secretion in sHPT. Polymorphism in CaSR gene (CASR) influences Ca-related parameters, however it was not shown in HD patients for CASR rs7652589. The minor allele at this polymorphism modifies the binding sites of transcription factors and CaSR expression...
October 14, 2016: Scientific Reports
Harry Z E Greenberg, Kazi S Jahan, Jian Shi, W-S Vanessa Ho, Anthony P Albert
The present study investigates the effect of commonly used negative and positive allosteric modulators of the calcium-sensing receptor (CaSR) on vascular reactivity. In wire myography studies, increasing [Ca(2+)]o from 1mM to 6mM induced concentration-dependent relaxations of methoxamine-induced pre-contracted rabbit mesenteric arteries, with 6mM [Ca(2+)]o producing almost complete relaxation. [Ca(2+)]o-induced relaxations were attenuated in the presence of the calcilytics Calhex-231 and NPS 2143, and abolished by the removal of the endothelium...
October 8, 2016: European Journal of Pharmacology
G Díaz-Soto, A Rocher, C García-Rodríguez, L Núñez, C Villalobos
The extracellular calcium-sensing receptor (CaSR) is a unique G protein-coupled receptor (GPCR) activated by extracellular Ca(2+) and by other physiological cations including Mg(2+), amino acids, and polyamines. CaSR is the most important master controller of the extracellular Ca(2+) homeostatic system being expressed at high levels in the parathyroid gland, kidney, gut and bone, where it regulates parathyroid hormone (PTH) secretion, vitamin D synthesis, and Ca(2+) absorption and resorption, respectively. Gain and loss of function mutations in the CaSR are responsible for severe disturbances in extracellular Ca(2+) metabolism...
2016: International Review of Cell and Molecular Biology
Fadil M Hannan, Valerie N Babinsky, Rajesh V Thakker
The extracellular calcium (Ca(2+) o)-sensing receptor (CaSR) is a family C G protein-coupled receptor, which detects alterations in Ca(2+) o concentrations and modulates parathyroid hormone secretion and urinary calcium excretion. The central role of the CaSR in Ca(2+) o homeostasis has been highlighted by the identification of mutations affecting the CASR gene on chromosome 3q21.1. Loss-of-function CASR mutations cause familial hypocalciuric hypercalcaemia (FHH), whereas gain-of-function mutations lead to autosomal dominant hypocalcaemia (ADH)...
October 2016: Journal of Molecular Endocrinology
P Chen, P Olsson Gisleskog, J J Perez-Ruixo, J Xiao, J Wilkins, A Narayanan, J P Gibbs, M Melhem
Etelcalcetide is a novel calcimimetic in development for the treatment of secondary hyperparathyroidism (SHPT). A population pharmacokinetic/pharmacodynamic (PK/PD) model was developed relating etelcalcetide exposures to markers of efficacy (parathyroid hormone [PTH]) and safety (calcium) using data from three clinical studies. The semimechanistic model was developed that included allosteric activation pharmacology and understanding of calcium homeostasis. The temporal profiles for all biomarkers were well described by the model...
September 2016: CPT: Pharmacometrics & Systems Pharmacology
Jordi Bover, Pablo Ureña-Torres, José Luis Górriz, María Jesús Lloret, Iara da Silva, César Ruiz-García, Pamela Chang, Mariano Rodríguez, José Ballarín
Cardiovascular (CV) calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD) and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD-MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating) its progression with iatrogenic manoeuvres...
August 29, 2016: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
Pia Villarroel, Pamela Mattar, Amanda D'Espessailles, Marco Arrese, Andrea Arreguin, Cecilia Fuentes, Marcela Reyes, Mariana Cifuentes
The calcium sensing receptor (CaSR) is expressed in human adipose cells, and its activation may associate with adipose tissue (AT) dysfunction. We evaluated whether CaSR stimulation influences adipocyte triglyceride (TG) and fatty acid binding protein 4 (aP2) content, and hepatocyte TGs and proinflammatory cytokine expression. The effect of the calcimimetic cinacalcet on TGs (fluorimetry), lipogenic genes (qPCR) and aP2 (immunoblot) was evaluated in LS14 adipocytes or AT. In the human HepG2 hepatic cell line, we assessed CaSR expression and cinacalcet effect on TGs and lipogenic and proinflammatory genes...
October 1, 2016: Archives of Biochemistry and Biophysics
Corrado Vitale, Francesca Bermond, Amelia Rodofili, Giorgio Soragna, Cristina Marcuccio, Alberto Tricerri, Martino Marangella
Primary hyperparathyroidism (PHPT) may favor nephrolithiasis mainly through an increase in calcium and phosphate urinary excretion. Cinacalcet exhibits good efficacy to control hypercalcemia in PHPT, but it is not so far known whether it might be a useful tool to prevent stone recurrences. Of 67 patients with PHPT and recurrent nephrolithiasis, 55 underwent parathyroidectomy (PTX) and 12, not eligible to PTX, were prescribed Cinacalcet. All the patients were evaluated for mineral metabolism, including estimation of state of saturation for calcium oxalate (CaOx) and brushite (bsh), both at baseline and after either PTX or Cinacalcet...
July 2016: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
Jacek Zawierucha, Jolanta Małyszko, Jacek Małyszko, Teresa Dryl-Rydzyńska, Tomasz Prystacki, Wojciech Marcinkowski
Secondary hyperparathyroidism (sHPT) is a common complication being a consequence of metabolic disorders associated with chronic kidney disease (CKD). Treatment of the sHPT should lead to calcium-phosphate management stabilization and parathyroid hormone levels reduction. The phosphate binders, synthetic vitamin D analogs and calcimimetics are used in sHPT treatment. In this paper we analyzed the results of three month paricalcitol treatment of 36 hemodialysis patients with sHPT (serum iPTH> 500 pg/ml). 11 patients have additionally received cinacalcet...
2016: Przegla̧d Lekarski
Priyesh Chauhan, Neil J Gittoes, Tarekegn Geberhiwot
A man aged 72 years with long-standing primary hyperparathyroidism (HPT), a background of recurrent bilateral renal stones and failed parathyroid surgery is described. During the 27 months preceding treatment, episodes of renal colic became increasingly frequent and he required multiple surgical interventions. Given the lack of medical therapies to definitively treat his symptoms, he was started on a trial of the calcimimetic, Cinacalcet. Cinacalcet has previously been shown to reduce hypercalcaemia in patients with primary HPT...
2016: BMJ Case Reports
Raju Subramanian, Xiaochun Zhu, M Benjamin Hock, Bethlyn J Sloey, Benjamin Wu, Sarah F Wilson, Ogo Egbuna, J Greg Slatter, Jim Xiao, Gary L Skiles
Etelcalcetide (AMG 416) is a novel synthetic peptide calcium-sensing receptor activator in clinical development as an intravenous calcimimetic for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on hemodialysis. Etelcalcetide is composed of seven D-aminoacids with an L-cysteine linked to a D-cysteine by a disulfide bond. A single intravenous dose of [(14)C]etelcalcetide (10 mg; 26.3 kBq; 710 nCi) was administered to patients with CKD on hemodialysis to elucidate the pharmacokinetics, biotransformation, and excretion of etelcalcetide in this setting...
August 12, 2016: Clinical Pharmacokinetics
Noah K Yuen, Shubha Ananthakrishnan, Michael J Campbell
Renal hyperparathyroidism (rHPT) is a common complication of chronic kidney disease characterized by elevated parathyroid hormone levels secondary to derangements in the homeostasis of calcium, phosphate, and vitamin D. Patients with rHPT experience increased rates of cardiovascular problems and bone disease. The Kidney Disease: Improving Global Outcomes guidelines recommend that screening and management of rHPT be initiated for all patients with chronic kidney disease stage 3 (estimated glomerular filtration rate, < 60 mL/min/1...
2016: Permanente Journal
Willemijn Y van der Plas, Anton F Engelsman, Akin Özyilmaz, Anouk N van der Horst-Schrivers, Kornelis Meijer, Gooitzen M van Dam, Robert A Pol, Martin H de Borst, Schelto Kruijff
BACKGROUND: Hyperparathyroidism (HPT), both secondary and tertiary, is common in patients with end-stage renal disease, and is associated with severe bone disorders, cardiovascular complications, and increased mortality. Since the introduction of calcimimetics in 2004, treatment of HPT has shifted from surgery to predominantly medical therapy. OBJECTIVE: The aim of this study was to evaluate the impact of this change of management on the HPT patient population before undergoing (sub-)total parathyroidectomy (PTx)...
July 26, 2016: Annals of Surgical Oncology
Rosemary Masterson, Susan Blair, Kevan R Polkinghorne, Kenneth K Lau, Michael Lian, Boyd J Strauss, John G Morgan, Peter Kerr, Nigel D Toussaint
Introduction Higher calcium dialysate is recommended for quotidian nocturnal hemodialysis (NHD) (≥6 nights/week) to maintain bone health. It is unclear what the optimal calcium dialysate concentration should be for alternate night NHD. We aimed to determine the effect of low calcium (LC) versus high calcium (HC) dialysate on cardiovascular and bone parameters in this population. Methods A randomized controlled trial where participants were randomized to LC (1.3 mmol/L, n = 24) or HC dialysate (1.6 or 1...
June 30, 2016: Hemodialysis International
David Granjon, Olivier Bonny, Aurélie Edwards
We developed a model of calcium homeostasis in the rat in order to better understand the impact of dysfunctions such as primary hyperparathyroidism and vitamin D deficiency on calcium balance. The model accounts for the regulation of calcium intestinal uptake, bone resorption, and renal reabsorption by parathyroid hormone (PTH), vitamin D3, and Ca2+ itself. It is the first such model to incorporate recent findings regarding the role of the calcium sensing receptor (CaSR) in the kidney, the presence of a rapidly exchangeable pool in bone, and the delayed response of vitamin D3 synthesis...
June 29, 2016: American Journal of Physiology. Renal Physiology
Zdeněk Adam, Karel Starý, Jozef Kubinyi, Kateřina Zajíčková, Zdeněk Řehák, Renata Koukalová, Miroslav Tomíška, Martina Doubková, Jiří Prášek, Eva Pourová, Zdeňka Čermáková, Luděk Pour, Marta Krejčí, Viera Sandecká, Eva Ševčíková, Sabina Ševčíková, Zdeněk Král, Aleš Čermák
UNLABELLED: The concentration of calcium is carefully maintained under physiological conditions with parathormone, calcitonin and 1,25-dihydroxyvitamin D at appropriate levels. There are multiple causes that may bring about increased concentrations of calcium which exceed physiological values. Increased production of parathormone in parathyroid glands is only one of the possible causes. Malignant diseases are a very frequent cause of hypercalcemia, due to their creating mediators which stimulate osteoclasts and thereby osteolysis...
2016: Vnitr̆ní Lékar̆ství
Ahmed Chelouan, Rocío Recio, Lorenzo G Borrego, Eleuterio Álvarez, Noureddine Khiar, Inmaculada Fernández
A new type of chiral sulfinamide phosphinate catalysts with up to three stereogenic centers, readily accessible from commercially available starting materials, is reported. The naphthyl derivative SulPhos proved to be highly efficient in the organocatalytic asymmetric imine reduction, leading to a wide range of arylmethylamines in high yields with up to 99% ee under 10% catalyst loading. The synthetic utility of this method was demonstrated by the expeditious enantioselective synthesis of the calcimimetic NPS-R568...
July 1, 2016: Organic Letters
Nobuo Nagano, Takaaki Tsutsui
Calcimimetics act as positive allosteric modulators of the calcium-sensing receptor (CaSR), thereby decreasing parathyroid hormone (PTH) secretion from the parathyroid glands. On the other hand, negative allosteric modulators of the CaSR with stimulatory effect on PTH secretion are termed calcilytics. The calcimimetic cinacalcet hydrochloride (cinacalcet) is the world's first allosteric modulator of G protein-coupled receptor to enter the clinical market. Cinacalcet just tunes the physiological effects of Ca(2+), an endogenous ligand, therefore, shows high selectivity and low side effects...
June 2016: Clinical Calcium
Daniela Riccardi, Giovanna Valenti
The ability to monitor changes in the ionic composition of the extracellular environment is a crucial feature that has evolved in all living organisms. The cloning and characterization of the extracellular calcium-sensing receptor (CaSR) from the mammalian parathyroid gland in the early 1990s provided the first description of a cellular, ion-sensing mechanism. This finding demonstrated how cells can detect small, physiological variations in free ionized calcium (Ca(2+)) in the extracellular fluid and subsequently evoke an appropriate biological response by altering the secretion of parathyroid hormone (PTH) that acts on PTH receptors expressed in target tissues, including the kidney, intestine, and bone...
July 2016: Nature Reviews. Nephrology
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