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https://www.readbyqxmd.com/read/28742508/clinical-characterization-of-a-novel-calcium-sensing-receptor-genetic-alteration-in-a-greek-patient-with-autosomal-dominant-hypocalcemia-type-1
#1
Anna Papadopoulou, Evangelia Gole, Katerina Melachroinou, Theoni Trangas, Evaggelia Bountouvi, Anastasios Papadimitriou
OBJECTIVE: Autosomal dominant hypocalcemia (ADH) is a rare familial or sporadic syndrome associated with activating mutations in the calcium sensing receptor (CaSR) gene. The aim of this study was to assess the functional significance of a novel CaSR mutation and, moreover, to present the clinical characteristics and the bone mineral density (BMD) progression from early childhood to late puberty in a patient with ADH. DESIGN: Genetic analysis of the CaSR gene was performed in a patient who presented in the neonatal period with hypocalcemic seizures and biochemical features of ADH...
April 2017: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28741586/a-new-mutation-in-the-calcium-sensing-receptor-gene-causing-hypocalcaemia-case-report-of-a-father-and-two-sons
#2
M K Schoutteten, B Bravenboer, S Seneca, K Stouffs, B Velkeniers
BACKGROUND: Regulation of calcium is mediated by parathyroid hormone (PTH) and 1.25-dihydroxyvitamine D3. The calcium-sensing receptor (CaSR) regulates PTH release by a negative feedback system. Gain-of-function mutations in the CaSR gene reset the calcium-PTH axis, leading to hypocalcaemia. PATIENTS AND METHODS: We analysed a family with hypocalcaemia. The proband was a 47-year-old man (index, patient I1), who presented with paraesthesias in both limbs. He has two sons (patient II1 a nd I I2)...
July 2017: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/28731996/-pancreatitis-genes-and-islet-cells-auto-transplant-updates-and-new-horizons
#3
Edgardo D Rivera Rivera
Pancreatitis is an inflammation of the pancreas that can progress from an acute presentation to an acute recurring presentation and eventually to chronic pancreatitis, which is characterized by irreversible morphological changes and scarring of the pancreas. The entity known as hereditary pancreatitis has been recognized in the literature for years and certainly the discovery of the PRSS1 gene in 1996 marked the beginning of a new era of genetic discoveries associated with the disease. Since then, multiple genes have been described as the causing agents of pancreatitis or disease modifiers, some of the most important ones being the PRSS1, SPINK1, CFTR, CASR, CTRC, CLDN2, and CPA1...
April 2017: Revista de Gastroenterología del Perú: órgano Oficial de la Sociedad de Gastroenterología del Perú
https://www.readbyqxmd.com/read/28720371/genetic-risk-factors-for-idiopathic-urolithiasis-a-systematic-review-of-the-literature-and-causal-network-analysis
#4
REVIEW
Kazumi Taguchi, Takahiro Yasui, Dawn Schmautz Milliner, Bernd Hoppe, Thomas Chi
CONTEXT: Urolithiasis has a high prevalence and recurrence rate. Prevention is key to patient management, but risk stratification is challenging. In particular, genetic predisposition for urinary stones is not fully understood. OBJECTIVE: To review current evidence of potential causative genes for idiopathic urolithiasis and map their relationships to one another. This evidence is essential for future establishment of molecular targeted therapy. EVIDENCE ACQUISITION: A systematic literature review from 2007 to 2017 was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines...
February 2017: European Urology Focus
https://www.readbyqxmd.com/read/28712411/calcium-sensing-receptor-casr-is-involved-in-porcine-in-vitro-fertilisation-and-early-embryo-development
#5
C Liu, Y Liu, K Larsen, Y P Hou, H Callesen
It has been demonstrated that extracellular calcium is necessary in fertilisation and embryo development but the mechanism is still not well understood. The present study mainly focussed on the extracellular calcium effector called the calcium-sensing receptor (CASR) and examined its expression in porcine gametes and embryos and its function during fertilisation and early embryo development. By using reverse transcription polymerase chain reaction, CASR was found to be expressed in porcine oocytes, spermatozoa and embryos at different developmental stages...
July 17, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28699522/targeting-human-astrocytes-calcium-sensing-receptors-for-treatment-of-alzheimer-s-disease
#6
Anna Chiarini, Ubaldo Armato, James F Whitfield, Ilaria Dal Pra
Understanding the pathophysiology of Alzheimer's disease (AD) in the principal human neural cells is necessary for finding therapeutics for this illness. To help do this, we have been using freshly cultured functionally normal cerebral cortical adult human astrocytes (NAHAs) and postnatal neurons. The findings show that amyloid-β oligomers (Aβ-os) binding to calcium-sensing receptors (CaSRs) on NAHAs and neuron surfaces trigger signals capable of driving AD pathogenesis. This Aβ•CaSR signalling shifts the amyloid precursor protein (APP) from its α-secretase shedding producing neurotrophic/neuroprotective soluble (s)APPα to its β-secretase cleaving engendering AD-driving Aβ42/Aβ42-os peptides...
July 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28691814/intervention-of-dietary-dipeptide-gamma-l-glutamyl-l-valine-%C3%AE-ev-ameliorates-inflammatory-response-in-a-mouse-model-of-lps-induced-sepsis
#7
MacKenzie E Chee, Kaustav Majumder, Yoshinori Mine
Sepsis, the systemic inflammatory response syndrome (SIRS) with infection is one of the leading causes of death in critically ill patients in the developed world due to the lack of effective antisepsis treatments. This study examined the efficacy of dietary dipeptide gamma-l-glutamyl-l-valine (γ-EV), which was characterized previously as an anti-inflammatory peptide, in an LPS-induced mouse model of sepsis. BALB/c mice were administered γ-EV via oral gavage followed by an intraperitoneal injection of LPS to induce sepsis...
July 10, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28690912/atypical-skeletal-manifestations-of-rickets-in-a-familial-hypocalciuric-hypercalcemia-patient
#8
Bo Wu, Ou Wang, Yan Jiang, Mei Li, Xiaoping Xing, Weibo Xia
Familial hypocalciuric hypercalcemia (FHH) is caused by inactivating mutations in the calcium-sensing receptor (CaSR) gene. The loss of function of CaSR presents with rickets as the predominant skeletal abnormality in mice, but is rarely reported in humans. Here we report a case of a 16-year-old boy with FHH who presented with skeletal manifestations of rickets. To identify the possible pathogenic mutation, the patient was evaluated clinically, biochemically, and radiographically. The patient and his family members were screened for genetic mutations...
2017: Bone Research
https://www.readbyqxmd.com/read/28676564/calcium-intake-and-risk-of-colorectal-cancer-according-to-expression-status-of-calcium-sensing-receptor-casr
#9
Wanshui Yang, Li Liu, Yohei Masugi, Zhi Rong Qian, Reiko Nishihara, NaNa Keum, Kana Wu, Stephanie Smith-Warner, Yanan Ma, Jonathan A Nowak, Fatemeh Momen-Heravi, Libin Zhang, Michaela Bowden, Teppei Morikawa, Annacarolina da Silva, Molin Wang, Andrew T Chan, Charles S Fuchs, Jeffrey A Meyerhardt, Kimmie Ng, Edward Giovannucci, Shuji Ogino, Xuehong Zhang
OBJECTIVE: Although evidence suggests an inverse association between calcium intake and the risk of colorectal cancer, the mechanisms remain unclear. The calcium-sensing receptor (CASR) is expressed abundantly in normal colonic epithelium and may influence carcinogenesis. We hypothesized that calcium intake might be associated with lower risk of CASR-positive, but not CASR-negative, colorectal cancer. DESIGN: We assessed tumour CASR protein expression using immunohistochemistry in 779 incident colon and rectal cancer cases that developed among 136 249 individuals in the Nurses' Health Study and Health Professionals Follow-Up Study...
July 4, 2017: Gut
https://www.readbyqxmd.com/read/28633902/calcium-sensing-receptor-initiating-cystathionine-gamma-lyase-hydrogen-sulfide-pathway-to-inhibit-platelet-activation-in-hyperhomocysteinemia-rat
#10
Yuwen Wang, Ziqing Zhao, Sa Shi, Fei Gao, Jichao Wu, Shiyun Dong, Weihua Zhang, Yanhong Liu, Xin Zhong
Hyperhomocysteinemia (HHcy, high homocysteine) induces the injury of endothelial cells (ECs). Hydrogen sulfide (H2S) protects ECs and inhibits the activation of platelets. Calcium-sensing receptor (CaSR) regulates the production of endogenous H2S. However, whether CaSR inhibits the injury of ECs and the activation of platelets by regulating the endogenous cystathionine-gamma-lyase (CSE, a major enzyme that produces H2S)/H2S pathway in hyperhomocysteinemia has not been previously investigated. Here, we tested the ultrastructure alterations of ECs and platelets, the changes in the concentration of serum homocysteine and the parameters of blood of hyperhomocysteinemia rats were measured...
June 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28630081/calcium-sensing-receptor-genotype-and-response-to-cinacalcet-in-patients-undergoing-hemodialysis
#11
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/28623466/increases-in-circulating-amino-acids-with-in-feed-antibiotics-correlated-with-gene-expression-of-intestinal-amino-acid-transporters-in-piglets
#12
Miao Yu, Chunlong Mu, Yuxiang Yang, Chuanjian Zhang, Yong Su, Zan Huang, Kaifan Yu, Weiyun Zhu
In-feed antibiotics have been commonly used to promote the growth performance of piglets. The antibiotics can increase protein utilization, but the underlying mechanism is largely unknown. The present study investigated the effects of in-feed antibiotics on intestinal AA transporters and receptors to test the hypothesis that the alteration of circulating AA profiles may be concomitant with the change of intestinal AA transporters and receptors. Sixteen litters of piglets at day 7 started to receive creep feed with (Antibiotic) or without (Control) antibiotic...
June 16, 2017: Amino Acids
https://www.readbyqxmd.com/read/28615947/treatment-of-secondary-hyperparathyroidism-the-clinical-utility-of-etelcalcetide
#13
REVIEW
Mario Cozzolino, Andrea Galassi, Ferruccio Conte, Michela Mangano, Luca Di Lullo, Antonio Bellasi
Secondary hyperparathyroidism (SHPT), a very frequent, severe, and worsening complication of chronic kidney disease, is characterized by high serum parathyroid hormone (PTH), parathyroid gland hyperplasia, and disturbances in mineral metabolism. Clinically, SHPT shows renal osteodystrophy, vascular calcification, cardiovascular damage, and fatal outcome. Calcium-sensing receptor (CaSR) is the main physiological regulator of PTH secretion; its activation by calcium rapidly inhibits PTH. Another important player in regulating mineral metabolism is vitamin D receptor (VDR), which is under the influence of vitamin D and influences the intestinal absorption of calcium and phosphate, PTH gene expression, and bone calcium mobilization...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28609763/calcium-sensing-receptor-genetic-polymorphisms-and-risk-of-developing-nephrolithiasis-in-a-chinese-population
#14
Qi Ding, Bo Fan, Ying Shi, Zhijiang Fan, Li Ding, Feng Li, Wenjian Tu, Xiaohua Jin, Chao Qin, Qiang Cao, Qinbo Yuan, Jing Wang, Jun Ouyang
OBJECTIVE: To evaluate the association between calcium-sensing receptor (CaSR) Arg990Gly (rs1042636, A > G), Ala986Ser (rs1801725, G > T) polymorphisms, and urolithiasis risk. METHODS: Polymorphisms mentioned above were genotyped in a hospital-based case-control study of 615 patients diagnosed with nephrolithiasis and 315 kidney stone-free controls in a Chinese population using the SNaPshot method. RESULTS: The results indicated a significantly increased risk associated with CaSR Arg990Gly GG genotypes (OR 1...
June 14, 2017: Urologia Internationalis
https://www.readbyqxmd.com/read/28597792/implications-of-the-calcium-sensing-receptor-in-ischemia-reperfusion
#15
François Paquot, Justine Huart, Jean-Olivier Defraigne, Jean-Marie Krzesinski, François Jouret
The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) which was first isolated from bovine parathyroid glands. Its complex structure has been well characterized, which helped to better understand its function. The CaSR activity can be modulated by various ligands, either activators (also called "calcimimetics") or inhibitors (or "calcilytics"). The main role of the CaSR concerns Ca(2+) homeostasis. In bone, intestine and kidney, the CaSR acts as a sensor for extracellular ionized Ca(2+) concentration ([Ca(2+)]e) to keep it stable...
April 2017: Acta Cardiologica
https://www.readbyqxmd.com/read/28575322/mutant-mice-with-calcium-sensing-receptor-casr-activation-have-hyperglycemia-that-is-rectified-by-calcilytic-therapy
#16
Valerie N Babinsky, Fadil M Hannan, Reshma D Ramracheya, Quan Zhang, M Andrew Nesbit, Alison Hugill, Liz Bentley, Tertius A Hough, Elizabeth Joynson, Michelle Stewart, Abhishek Aggarwal, Maximilian Prinz-Wohlgenannt, Caroline M Gorvin, Enikö Kallay, Sara Wells, Roger D Cox, Duncan Richards, Patrik Rorsman, Rajesh V Thakker
The calcium-sensing receptor (CaSR) is a family C G-protein-coupled receptor (GPCR) that plays a pivotal role in extracellular calcium homeostasis. The CaSR is also highly expressed in pancreatic islet α- and β-cells that secrete glucagon and insulin, respectively. To determine whether the CaSR may influence systemic glucose homeostasis, we characterized a mouse model with a germline gain-of-function CaSR mutation, Leu723Gln, referred to as Nuclear flecks (Nuf). Heterozygous- (CasrNuf/+) and homozygous-affected (CasrNuf/Nuf) mice were shown to have hypocalcemia in association with impaired glucose tolerance and insulin secretion...
June 2, 2017: Endocrinology
https://www.readbyqxmd.com/read/28518143/calcium-sensing-receptor-protects-high-glucose-induced-energy-metabolism-disorder-via-blocking-gp78-ubiquitin-proteasome-pathway
#17
Yuehong Wang, Ping Gao, Can Wei, Hongzhu Li, Li Zhang, Yajun Zhao, Bo Wu, Ye Tian, Weihua Zhang, Lingyun Wu, Rui Wang, Changqing Xu
Diabetic cardiomyopathy (DCM) is a major complication and fatal cause of the patients with diabetes. The calcium sensing receptor (CaSR) is a G protein-coupled receptor, which is involved in maintaining calcium homeostasis, regulating cell proliferation and apoptosis, and so on. In our previous study, we found that CaSR expression, intracellular calcium levels and cardiac function were all significantly decreased in DCM rats; however, the exact mechanism are not clear yet. The present study revealed the protective role of CaSR in myocardial energy metabolism disorder induced by high glucose (HG) as well as the underlying mechanism...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28515208/glucocorticoid-responsive-lymphocytic-parathyroiditis-and-hypocalciuric-hypercalcemia-due-to-autoantibodies-against-the-calcium-sensing-receptor-a-case-report-and-literature-review
#18
Li Song, Liping Liu, R Tyler Miller, Shirley X Yan, Nancy Jackson, Shelby A Holt, Naim M Maalouf
OBJECTIVE: Autoimmune lymphocytic parathyroiditis and acquired hypocalciuric hypercalcemia associated with autoantibodies against the calcium-sensing receptor (anti-CaSR) are rare and poorly understood conditions. Here, we describe a patient with acquired parathyroid hormone (PTH)-dependent hypercalcemia with associated hypocalciuria, found to have true lymphocytic parathyroiditis on histopathology, and circulating anti-CaSR antibodies in serum. DESIGN AND METHODS: A 64-year-old woman was referred to our clinic for persistent hypercalcemia after a subtotal parathyroidectomy...
July 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28508378/population-pharmacokinetic-and-pharmacodynamic-modeling-of-etelcalcetide-in-patients-with-chronic-kidney-disease-and-secondary-hyperparathyroidism-receiving-hemodialysis
#19
Ping Chen, Adimoolam Narayanan, Benjamin Wu, Per Olsson Gisleskog, John P Gibbs, Andrew T Chow, Murad Melhem
INTRODUCTION: Etelcalcetide is a novel calcimimetic that binds and activates calcium-sensing receptors (CaSRs) for the treatment of secondary hyperparathyroidism (SHPT). METHODS: To assess titrated dosing regimens, population pharmacokinetic (PK) and PK/pharmacodynamic (PKPD) modeling of etelcalcetide was performed using NONMEM 7.2. In this analysis, plasma etelcalcetide, serum parathyroid hormone (PTH) and calcium (Ca) concentration-time data were collected from five phase I, II, and III clinical trials following single or multiple intravenous doses of etelcalcetide ranging from 2...
May 15, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28506888/calcium-sensing-receptor-erk-signaling-promotes-odontoblastic-differentiation-of-human-dental-pulp-cells
#20
Hiroyuki Mizumachi, Shinichiro Yoshida, Atsushi Tomokiyo, Daigaku Hasegawa, Sayuri Hamano, Asuka Yuda, Hideki Sugii, Suguru Serita, Hiromi Mitarai, Katsuaki Koori, Naohisa Wada, Hidefumi Maeda
Activation of the G protein-coupled calcium-sensing receptor (CaSR) has crucial roles in skeletal development and bone turnover. Our recent study has identified a role for activated CaSR in the osteogenic differentiation of human periodontal ligament stem cells. Furthermore, odontoblasts residing inside the tooth pulp chamber play a central role in dentin formation. However, it remains unclear how CaSR activation affects the odontoblastic differentiation of human dental pulp cells (HDPCs). We have investigated the odontoblastic differentiation of HDPCs exposed to elevated levels of extracellular calcium (Ca) and strontium (Sr), and the contribution of CaSR and the L-type voltage-dependent calcium channel (L-VDCC) to this process...
May 12, 2017: Bone
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