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Cinacalcet

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https://www.readbyqxmd.com/read/29345311/calcium-sensing-receptor-activates-the-nlrp3-inflammasome-in-ls14-preadipocytes-mediated-by-erk1-2-signaling
#1
Amanda D'Espessailles, Yuly A Mora, Cecilia Fuentes, Mariana Cifuentes
The study of the mechanisms that trigger inflammation in adipose tissue is key to understanding and preventing the cardiometabolic consequences of obesity. We have proposed a model where activation of the G protein-coupled calcium sensing receptor (CaSR) leads to inflammation and dysfunction in adipose cells. Upon activation, CaSR can mediate the expression and secretion of proinflammatory factors in human preadipocytes, adipocytes and adipose tissue explants. One possible pathway involved in CaSR-induced inflammation is the activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome, that promotes maturation and secretion of interleukin (IL)-1β...
January 18, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29325022/large-scale-exome-datasets-reveal-a-new-class-of-adaptor-related-protein-complex-2-sigma-subunit-ap2%C3%AF-mutations-located-at-the-interface-with-the-ap2-alpha-subunit-that-impair-calcium-sensing-receptor-signalling
#2
Caroline M Gorvin, Raghu Metpally, Victoria J Stokes, Fadil M Hannan, Sarath B Krishnamurthy, John D Overton, Jeffrey G Reid, Gerda E Breitwieser, Rajesh V Thakker
Mutations of the sigma subunit of the heterotetrameric adaptor-related protein complex 2 (AP2σ) impair signalling of the calcium-sensing receptor (CaSR), and cause familial hypocalciuric hypercalcaemia type 3 (FHH3). To date, FHH3-associated AP2σ mutations have only been identified at one residue, Arg15. We hypothesized that additional rare AP2σ variants may also be associated with altered CaSR function and hypercalcaemia, and sought for these by analysing >111,995 exomes (>60,706 from ExAc and dbSNP, and 51,289 from the Geisinger Health System-Regeneron DiscovEHR dataset which also contains clinical data)...
January 9, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29313395/formulation-optimization-and-pharmacokinetics-evaluation-of-oral-self-microemulsifying-drug-delivery-system-for-poorly-water-soluble-drug-cinacalcet-and-no-food-effect
#3
Mengyuan Cao, Xu Xue, Xixi Pei, Yiwen Qian, Lan Liu, Lili Ren, Guoguang Chen
The present research indicated that a new self-microemulsifying drug delivery systems (SMEDDS) were used to reduce the food effect of poorly water-soluble drug cinacalcet and enhance the bioavailability in beagle dogs by oral gavage. Ethyl oleate, OP-10 and PEG-200 was selected as the oil phase, surfactant and co-surfactant of cinacalcet-SMEDDS by the solubility and phase diagram studies. Central Composite Design-Response Surface Methodology was used to determine the ratio of surfactant and co-surfactant, the amount of oil for optimizing the SMEDDS formation...
January 9, 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29301445/gallstones-were-associated-with-the-gastrointestinal-adverse-events-of-cinacalcet-in-hemodialysis-patients-with-secondary-hyperparathyroidism
#4
Keiichi Otsuka, Yoichi Ohno, Joji Oshima
This study aimed to investigate the association of gastrointestinal (GI) adverse events of cinacalcet with gallstones in the hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). A total of 23 HD patients under the treatment with cinacalcet and 101 control patients were enrolled in this cross-sectional study. We investigated the prevalence of gallstones and the association of GI adverse events of cinacalcet with gallstones. The prevalence of gallstones was significantly higher in the HD patients with cinacalcet compared with the controls (47...
November 2018: Renal Failure
https://www.readbyqxmd.com/read/29238762/etelcalcetide-injectable-calcimimetic-for-the-treatment-of-secondary-hyperparathyroidism-in-hemodialysis-dependent-patients
#5
P A Ureña Torres, J Bover, M Cohen-Solal
Chronic kidney disease is associated with mineral and bone disorders that are now considered as a syndrome. One of the major complications of this syndrome is secondary hyperparathyroidism (SHPT). SHPT increases bone turnover and the risk of fracture. SHPT is also associated with cardiovascular calcification and high mortality risk. The classical medical therapies of SHPT lack long-term efficacy and have undesirable effects on serum calcium and phosphate levels. Surgical parathyroidectomy is a radical therapeutic solution potentially exposing patients to a permanent state of hypoparathyroidism among other complications...
September 2017: Drugs of Today
https://www.readbyqxmd.com/read/29216631/effect-of-cinacalcet-combined-with-calcitriol-on-the-clinical-outcome-and-bone-metabolism-in-patients-on-hemodialysis-with-severe-secondary-hyperparathyroidism
#6
Fang Yuan, Xing Chen, Chang Wang, Zheng Li, Hong Liu
OBJECTIVE: To observe the clinical outcome and the effect of bone metabolism of cinacalcet combined with calcitriol in maintenance hemodialysis (MHD) patients with severe secondary hyperparathyroidism (SHPT). METHODS: Thirty MHD patients with SHPT were enrolled into the study. All patients were given cinacalcet 25-75 mg and 0.5 μg calcitriol daily. Serum Ca, P, intact parathyroid hormone (iPTH), and bone metabolic markers were measured. The clinical symptoms and their changes were investigated...
December 7, 2017: Blood Purification
https://www.readbyqxmd.com/read/29192005/successful-reversal-of-furosemide-induced-secondary-hyperparathyroidism-with-cinacalcet
#7
Tarak Srivastava, Shahryar Jafri, William E Truog, Judith Sebestyen VanSickle, Winston M Manimtim, Uri S Alon
Secondary hyperparathyroidism (SHPT) is a rare complication of furosemide therapy that can occur in patients treated with the loop diuretic for a long period of time. We report a 6-month-old 28-weeks premature infant treated chronically with furosemide for his bronchopulmonary dysplasia, who developed hypocalcemia and severe SHPT, adversely affecting his bones. Discontinuation of the loop diuretic and the addition of supplemental calcium and calcitriol only partially reversed the SHPT, bringing serum parathyroid hormone level down from 553 to 238 pg/mL...
December 2017: Pediatrics
https://www.readbyqxmd.com/read/29124559/hungry-bone-syndrome-two-weeks-after-starting-cinacalcet-a-call-for-caution
#8
Sahar H Koubar, Abd Assalam Qannus, Walid Medawar, Ali K Abu-Alfa
Cinacalcet is an effective and safe alternative to parathyroidectomy in end stage renal disease (ESRD) patients with secondary hyperparathyroidism. Hypocalcemia is a known complication of treatment that is usually readily reversible upon discontinuation of the drug. It rarely manifests severely and symptomatically requiring hospital admission. We present the case of a 55 year old man with severe, symptomatic and prolonged hypocalcemia that occurred 2 weeks after starting cinacalcet. Cinacalcet induced a state of pharmacological parathyroidectomy with subsequent hungry bone syndrome...
November 9, 2017: CEN Case Reports
https://www.readbyqxmd.com/read/29108515/long-term-use-of-cinacalcet-in-kidney-transplant-recipients-with-hypercalcemic-secondary-hyperparathyroidism-a-single-center-prospective-study
#9
Vasileios Zavvos, Lamprini Fyssa, Marios Papasotiriou, Evangelos Papachristou, Theodoros Ntrinias, Eirini Savvidaki, Dimitrios S Goumenos
OBJECTIVES: Persistent secondary hyperparathyroidism is common after successful kidney transplant, with concomitant hypercalcemia and hypophosphatemia potentially leading to reduced graft survival and increased cardiovascular risk. Cinacalcet, a calcimimetic agent that activates the calcium-sensing receptors in parathyroid glands, is a therapeutic option. In this study, we assessed the long-term treatment effects of cinacalcet for a period of up to 5 years in a cohort of kidney transplant recipients...
October 31, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29093248/-effect-of-cinacalcet-combined-with-low-dose-calcitriol-on-clinical-outcome-and-bone-metabolism-in-patients-with-severe-secondary-hyperparathyroidism
#10
Fang Yuan, Xing Chen, Chang Wang, An Zhou, Hong Liu
To observe the clinical outcome and the effect of the combination of cinacalcet hydrochloride with low-dose calcitriol on bone metabolism in maintenance hemodialysis (MHD) patients with severe secondary hyperparathyroidism (SHPT).
 Methods: Thirty SHPT patients were enrolled to receive treatment of cinacalcet combined with low-dose calcitriol, with inclusion criteria as follows: maintenance on MHD>6 months; serum intact parathyroid hormone (iPTH)>600 pg/mL; parathyroid glands with more than 1 nodules by ultrasonography; traditional therapy with no effects...
October 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29078759/endothelin-a-receptor-blocker-and-calcimimetic-in-the-adenine-rat-model-of-chronic-renal-insufficiency
#11
Suvi Törmänen, Ilkka Pörsti, Päivi Lakkisto, Ilkka Tikkanen, Onni Niemelä, Timo Paavonen, Jukka Mustonen, Arttu Eräranta
BACKGROUND: We studied whether endothelin receptor antagonist and calcimimetic treatments influence renal damage and kidney renin-angiotensin (RA) components in adenine-induced chronic renal insufficiency (CRI). METHODS: Male Wistar rats (n = 80) were divided into 5 groups for 12 weeks: control (n = 12), 0.3% adenine (Ade; n = 20), Ade + 50 mg/kg/day sitaxentan (n = 16), Ade + 20 mg/kg/day cinacalcet (n = 16), and Ade + sitaxentan + cinacalcet (n = 16)...
October 27, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/29067991/does-combination-of-paricalcitol-with-cinacalcet-in-secondary-hyperparathyroidism-in-hemodialysis-treatment-make-sense
#12
Jacek Zawierucha, Jolanta Małyszko, Jacek Małyszko, Tomasz Prystacki, Wojciech Marcinkowski, Teresa Dryl-Rydzyńska
INTRODUCTION    Secondary hyperparathyroidism (SHPT) is a common hormonal disorder associated with  chronic kidney disease (CKD). SHPT treatment should lead to reduction of parathormon concentration by calcimimetics or active vitamin D administration and calcium-phosphate metabolism stabilization. In the event of failure of conservative treatment complete or partial parathyroid resection should be considered.  OBJECTIVES    The aim of the study was assessement of beneficial effects of treatment with paricalcitol and cinacalcet simultaneously versus paricalcitol alone...
October 25, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/29064176/calciphylaxis-after-parathyroidectomy
#13
Sathish Karmegam, Anupkumar Shetty
A 60-year-old African American man with end stage renal disease on hemodialysis (HD) for the past 2.5 years developed severe hyperparathyroidism. Other past medical history included atrial fibrillation, type II diabetes mellitus, hypertension, gout, pericardial effusion needing pericardial window, deep vein thrombosis, mitral insufficiency, and cardiomyopathy with implantable cardioversion device placement. His parathyroid hormone (PTH) level peaked at 4,191 pg/mL despite being on cinacalcet, sevelamer, and paricalcitol...
October 2017: Hemodialysis International
https://www.readbyqxmd.com/read/29051042/bone-disease-in-primary-hyperparathyroidism
#14
Polyzois Makras, Athanasios D Anastasilakis
Primary hyperparathyroidism (PHPT) is a disease of high bone turnover, decreased bone mineral density (BMD) especially at cortical sites, and increased risk of fractures at all skeletal sites. Early diagnosis during the last decades resulted in milder forms of bone involvement. New methods of imaging and validation such as high resolution peripheral quantitative computed tomography and trabecular bone score provide evidence of disturbed bone microarchitecture and explain further the increased risk of fractures at both cortical and trabecular skeletal sites...
October 16, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29047366/the-use-of-cinacalcet-hinders-the-diagnosis-of-parathyroid-carcinoma-in-a-chronic-dialysis-patient-a-case-report
#15
Daisuke Takada, Tatsuo Tsukamoto, Miho Fuse, Shinpei Kada, Motoko Yanagita
BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common complication in patients receiving chronic dialysis therapy. Although cinacalcet can control parathyroid function and bone turnover, preventing ectopic calcification remains challenging. Cinacalcet can also suppress PTH secretion due to parathyroid carcinoma in the same way as it does for parathyroid hyperplasia in the uremic condition. We present a case of parathyroid carcinoma partially controlled by cinacalcet, in which tumorous calcinosis was successfully resolved by total parathyroidectomy...
October 18, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/29046478/cinacalcet-corrects-hypercalcemia-in-mice-with-an-inactivating-g%C3%AE-11-mutation
#16
Sarah A Howles, Fadil M Hannan, Caroline M Gorvin, Sian E Piret, Anju Paudyal, Michelle Stewart, Tertius A Hough, M Andrew Nesbit, Sara Wells, Stephen Dm Brown, Roger D Cox, Rajesh V Thakker
Loss-of-function mutations of GNA11, which encodes G-protein subunit α11 (Gα11), a signaling partner for the calcium-sensing receptor (CaSR), result in familial hypocalciuric hypercalcemia type 2 (FHH2). FHH2 is characterized by hypercalcemia, inappropriately normal or raised parathyroid hormone (PTH) concentrations, and normal or low urinary calcium excretion. A mouse model for FHH2 that would facilitate investigations of the in vivo role of Gα11 and the evaluation of calcimimetic drugs, which are CaSR allosteric activators, is not available...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/28993865/two-year-cortical-and-trabecular-bone-loss-in-ckd-5d-biochemical-and-clinical-predictors
#17
H H Malluche, M-C Monier-Faugere, G Blomquist, D L Davenport
This prospective two-year study of patients on chronic dialysis measured changes in bone mineral density (BMD). Patients with higher baseline BMD and shorter dialysis vintage lost more bone. Treatment with anti-hypertensives acting on the central nervous system was protective against bone loss. Baseline serum levels of sclerostin and bone-specific alkaline phosphatase predicted bone loss. INTRODUCTION: This prospective 2-year study of chronic kidney disease on dialysis (CKD-5D) patients assessed trabecular and cortical bone loss at the hip and spine and examined potential demographic, clinical, and serum biochemical predictors of bone loss...
October 9, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28992983/primary-hyperparathyroidism
#18
REVIEW
Manuel Muñoz-Torres, Antonia García-Martín
Primary hyperparathyroidism (PHPT) is a common endocrinological process, characterized by chronic elevation of serum concentrations of calcium and parathyroid hormone (PTH). Many years ago, the most frequent forms of clinical presentation were symptomatic renal or skeletal disease with moderate or severe hypercalcemia; however, currently, most patients have few symptoms and mild hypercalcemia. A new form of presentation called normocalcemic PHPT has also been described but clinical consequences are not well established...
October 6, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28991002/estimating-the-effect-of-preventable-treatment-discontinuation-on-health-outcomes
#19
M A Brookhart, D Reams, P J Dluzniewski, A Kshirsagar, L Walsh, B D Bradbury
BACKGROUND: There is increased interest in studying the effects of medication adherence on health outcomes. However, if patients appropriately stop treatment because of side effects and treatment failure, it is neither possible nor clinically meaningful to estimate the effect of full medication adherence. METHODS: We present an analysis designed to estimate the effect of non-medical (preventable) discontinuation of cinacalcet, an oral medication approved to treat secondary hyperparathyroidism in patients with end stage renal disease on dialysis on mortality and heart failure...
October 4, 2017: Epidemiology
https://www.readbyqxmd.com/read/28980761/parathyroid-nodular-hyperplasia-and-responsiveness-to-drug-therapy-in-renal-secondary-hyperparathyroidism-an-open-question
#20
REVIEW
Carlo Vulpio, Maurizio Bossola
The goal of the pharmacological therapy in secondary hyperparathyroidism (SHPT) is to reduce serum levels of parathyroid hormone and phosphorus, to correct those of calcium and vitamin D, to arrest or reverse the parathyroid hyperplasia. However, when nodular hyperplasia or an autonomous adenoma develops, surgery may be indicated. We reviewed the literature with the aim of defining if the echographic criteria predictive of unresponsiveness of SHPT to calcitriol therapy are valid also in the cinacalcet era and if drug therapy may reverse nodular hyperplasia of parathyroid gland (PTG)...
October 5, 2017: Therapeutic Apheresis and Dialysis
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