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https://www.readbyqxmd.com/read/29144803/endocrine-manifestations-of-primary-hyperoxaluria
#1
Shatha Murad, Yuval Eisenberg
OBJECTIVE: Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder of oxalate overproduction. It is associated with urolithiasis and nephrocalcinosis which progress to ESRD and systemic oxalosis. As oxalate deposits in tissues, non-parathyroid hormone (nonPTH) mediated hypercalcemia, oxalate osteopathy, primary hypothyroidism and primary hypogonadism develop. In this review, we will present a case of PH1 and provide an overview of this clinical entity and its endocrine manifestations...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29141920/parathyroid-hormone-related-protein-modulates-mice-mesangial-cells-inflammation-and-blunts-apoptosis-by-enhancing-cox-2-expression
#2
Mazène Hochane, Denis Raison, Catherine Coquard, Claire Béraud, Audrey Bethry, Sabrina Danilin, Thierry Massfelder, Mariette Barthelmebs
Mesangial cell (MC) injury is a prominent feature of glomerulonephritis. Activated MC secretes inflammatory mediators which induce cell apoptosis. Parathyroid hormone-related peptide (PTHrP) is a locally active cytokine that enhances cell survival and is upregulated by pro-inflammatory factors in many cell types. The aim of this study was to analyze the regulation of PTHrP expression by inflammatory cytokines, and to evaluate whether PTHrP itself acts as a pro-inflammatory and/or survival factor on male murine MC in primary culture...
November 15, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29125274/pseudohypoparathyroidism
#3
Luisella Cianferotti, Maria L Brandi
The term pseudohypoparathyroidism (PHP) refers to a spectrum of rare disorders of mineral metabolism, characterized by features due to end-organ resistance to PTH. The phenotypes of Albright hereditary osteodystrophy (AHO), originally described as associated to the disease, and progressive osseous heteroplasia, can be associated to the endocrine manifestations of hormonal resistance. Genetic or epigenetic alterations in the complex imprinted GNAS locus, encoding the alpha-subunit of the stimulatory G protein (GSα) and several other transcripts, give rise to the different forms oh PHP, which can be differentiated according to the phenotype, the response to PTH infusion and in vitro assays testing Gsα activity...
November 10, 2017: Minerva Endocrinologica
https://www.readbyqxmd.com/read/29122643/parathyroid-hormone-related-protein-concentration-in-human-serum-and-csf-correlates-with-age
#4
Mark M Kushnir, Lisa K Peterson, Frederick G Strathmann
BACKGROUND: Parathyroid Hormone-Related Protein (PTHrP) is involved in intracellular calcium (Ca) regulation, and has been demonstrated to participate in regulation of Ca in brain cells, activation of neurons, and modulation of pain. However, there are conflicting reports regarding the presence of PTHrP in CSF. DESIGN AND METHODS: PTHrP and Ca were quantified in paired CSF and serum samples using mass spectrometry-based methods. Associations between PTHrP and Ca concentrations with age, sex and concentrations of nine CSF diagnostic markers in a set of 140 paired serum and CSF patient samples were evaluated...
November 6, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/29113980/management-of-endocrine-disease-novel-anabolic-treatments-for-osteoporosis
#5
Ernesto Canalis
Skeletal anabolic agents enhance bone formation, which is determined by the number and function of osteoblasts. Signals that influence the differentiation and function of cells of the osteoblast lineage play a role in the mechanism of action of anabolic agents in the skeleton. Wnts induce the differentiation of mesenchymal stem cells toward osteoblasts, and insulin-like growth factor I (IGF-I) enhances the function of mature osteoblasts. The activity of Wnt and IGF-I is controlled by proteins that bind to the growth factor or to its receptors...
November 7, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29081380/paratharmone-related-protein-peptide-a-novel-prognostic-diagnostic-and-therapeutic-marker-in-head-neck-cancer
#6
S Sen, P Dasgupta, G Kamath, H S Srikanth
Parathyroid hormone-related protein (PTHrP) is a promising modality of assessment of different critical features of cancer. It is a protein member of parathyroid hormone family, secreted by certain physiologic cells and by malignant tumors in an increased amount. Recent studies have confirmed that PTHrP massively contributes to malignant behaviour of oral cancers-cell proliferation, migration and invasiveness. Strong correlation was found between PTHrP overexpression and local bone invasion and percentage of tumor cells in metastatic nodes...
November 3, 2017: Journal of Stomatology, Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/29073831/pthrp-gradients-affect-the-progression-of-mesenchymal-stem-cell-chondrogenesis-and-hypertrophy
#7
Niamh Fahy, Oliver Gardner, Mauro Alini, Martin James Stoddart
INTRODUCTION: Mesenchymal stem cells (MSCs) are considered a promising cell source for cartilage repair strategies due to their chondrogenic differentiation potential. However, their in-vitro tendency to progress towards hypertrophy limits their clinical use. This unfavourable result may be due to the fact that MSCs used in tissue engineering approaches are all at the same developmental stage, and have lost crucial spatial and temporal signalling cues. In this study, we sought to investigate the effect of a spatial parathyroid hormone-related protein (PTHrP) signalling gradient on the chondrogenic differentiation of MSCs and progression to hypertrophy...
October 26, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29067279/first-report-of-small-cell-lung-cancer-with-pthrp-induced-hypercalcemic-pancreatitis-causing-disconnected-duct-syndrome
#8
Eric M Montminy, Stephen W Landreneau, Jordan J Karlitz
Here we report a patient diagnosed with small cell lung cancer after first presenting with parathyroid hormone-related peptide-induced hypercalcemic pancreatitis and developed walled-off necrosis that resulted in disruption of the main pancreatic duct. Disconnected duct syndrome (DDS) is a rare syndrome that occurs when the main pancreatic duct exocrine flow is disrupted resulting in leakage of pancreatic enzymes and further inflammatory sequela. To date, no prior reports have described DDS occurring with paraneoplastic reactions...
October 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29064243/development-of-potent-protease-resistant-agonists-of-the-parathyroid-hormone-receptor-with-broad-%C3%AE-residue-distribution
#9
Ross W Cheloha, Bingming Chen, Niyanta N Kumar, Tomoyuki Watanabe, Robert G Thorne, Lingjun Li, Thomas J Gardella, Samuel H Gellman
The parathyroid hormone receptor 1 (PTHR1) is a member of the B-family of GPCRs; these receptors are activated by long polypeptide hormones and constitute targets of drug development efforts. Parathyroid hormone (PTH, 84 residues) and PTH-related protein (PTHrP, 141 residues) are natural agonists of PTHR1, and an N-terminal fragment of PTH, PTH(1-34), is used clinically to treat osteoporosis. Conventional peptides in the 20-40-mer length range are rapidly degraded by proteases, which may limit their biomedical utility...
October 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29056680/animal-models-of-cancer-associated-hypercalcemia
#10
REVIEW
Nicole A Kohart, Said M Elshafae, Justin T Breitbach, Thomas J Rosol
Cancer-associated hypercalcemia (CAH) is a frequently-occurring paraneoplastic syndrome that contributes to substantial patient morbidity and occurs in both humans and animals. Patients with CAH are often characterized by markedly elevated serum calcium concentrations that result in a range of clinical symptoms involving the nervous, gastrointestinal and urinary systems. CAH is caused by two principle mechanisms; humorally-mediated and/or through local osteolytic bone metastasis resulting in excessive calcium release from resorbed bone...
April 13, 2017: Veterinary Sciences
https://www.readbyqxmd.com/read/29050201/htlv-1-viral-oncogene-hbz-induces-osteolytic-bone-disease-in-transgenic-mice
#11
Alison K Esser, Daniel A Rauch, Jingyu Xiang, John C Harding, Nicole A Kohart, Michael H Ross, Xinming Su, Kevin Wu, Devra Huey, Yalin Xu, Kiran Vij, Patrick L Green, Thomas J Rosol, Stefan Niewiesk, Lee Ratner, Katherine N Weilbaecher
Adult T-cell leukemia/lymphoma (ATL) is an aggressive T cell malignancy that occurs in HTLV-1 infected patients. Most ATL patients develop osteolytic lesions and hypercalcemia of malignancy, causing severe skeletal related complications and reduced overall survival. The HTLV-1 virus encodes 2 viral oncogenes, Tax and HBZ. Tax, a transcriptional activator, is critical to ATL development, and has been implicated in pathologic osteolysis. HBZ, HTLV-1 basic leucine zipper transcription factor, promotes tumor cell proliferation and disrupts Wnt pathway modulators; however, its role in ATL induced osteolytic bone loss is unknown...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049872/optimal-dosing-and-delivery-of-pth-and-its-analogues-for-osteoporosis-and-hypoparathyroidism-translating-the-pharmacology
#12
REVIEW
D Tay, S Cremers, J P Bilezikian
In primary hyperparathyroidism (PHPT), bone loss results from the resorptive effects of excess parathyroid hormone (PTH). Under physiological conditions, PTH has actions that are more targeted to homeostasis and to bone accrual. The predominant action of PTH, either catabolic, anabolic, or homeostatic, can be understood in molecular and pharmacokinetic terms. When administered intermittently, PTH increases bone mass, but when present continuously and in excess (e.g., PHPT), bone loss ensues. This dual effect of PTH depends not only on the dosing regimen, continuous or intermittent, but also on how the PTH molecule interacts with various states of its receptor (PTH/PTHrP receptor) influencing downstream signaling pathways differentially...
October 19, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28954822/dual-roles-of-parathyroid-hormone-related-protein-in-tgf-%C3%AE-1-signaling-and-fibronectin-up-regulation-in-mesangial-cells
#13
Su-Zhen Wu, Si-Jun Yang, Hong-Min Chen, Fang-Fang Peng, Hong Yu, Joan C Krepinsky, Bai-Fang Zhang
Little is known about the cross-talk between parathyroid hormone (PTH) related protein (PTHrP) and TGF-β1 in mesangial cells (MCs). Our results showed that PTHrP treatment (≤3 h) induced internalization of PTH1R (PTH/PTHrP receptor)-TβRII (TGF-β type 2 receptor) complex and suppressed TGF-β1-mediated Smad2/3 activation and fibronectin (FN) up-regulation. However, prolonged PTHrP treatment (12-48 h) failed to induce PTH1R-TβRII association and internalization. Total protein levels of PTH1R and TβRII were unaffected by PTHrP treatment...
October 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28914969/autocrine-and-paracrine-regulation-of-the-murine-skeleton-by-osteocyte-derived-parathyroid-hormone-related-protein
#14
Niloufar Ansari, Patricia Wm Ho, Blessing Crimeen-Irwin, Ingrid J Poulton, Athena R Brunt, Mark R Forwood, Paola Divieti Pajevic, Jonathan H Gooi, T John Martin, Natalie A Sims
Parathyroid hormone-related protein (PTHrP) and parathyroid hormone (PTH) have N-terminal domains that bind a common receptor, PTHR1. N-terminal PTH (teriparatide) and now a modified N-terminal PTHrP (abaloparatide) are US Food and Drug Administration (FDA)-approved therapies for osteoporosis. In physiology, PTHrP does not normally circulate at significant levels, but acts locally, and osteocytes, cells residing within the bone matrix, express both PTHrP and the PTHR1. Because PTHR1 in osteocytes is required for normal bone resorption, we determined how osteocyte-derived PTHrP influences the skeleton...
September 15, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28901584/the-primary-cilium-as-a-signaling-nexus-for-growth-plate-function-and-subsequent-skeletal-development
#15
REVIEW
Emily R Moore, Christopher R Jacobs
The primary cilium is a solitary, antenna-like sensory organelle with many important roles in cartilage and bone development, maintenance, and function. The primary cilium's potential role as a signaling nexus in the growth plate makes it an attractive therapeutic target for diseases and disorders associated with bone development and maintenance. Many signaling pathways that are mediated by the cilium - such as Hh, Wnt, Ihh/PTHrP, TGFβ, BMP, FGF, and Notch - are also known to influence endochondral ossification, primarily by directing growth plate formation and chondrocyte behavior...
September 13, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28901272/disorders-of-mechanisms-of-calcium-metabolism-control-as-potential-risk-factors-of-prostate-cancer
#16
Dorota Skrajnowska, Barbara Bobrowska-Korczak, Andrzej Tokarz
Prostate cancer significantly affects the overall morbidity and mortality of malignant tumours in highly developed countries. Important risk factors include family predisposition and regional, racial and dietary determinants. The scientific literature contains a great deal of data on the role of calcium and dairy products in general in the process of neoplastic transformation of the prostate. This is most likely linked to the fact that changes in the concentration of calcium ions control such varied life processes as secretion of hormones and neurotransmitters, the level of cyclic nucleotides, and cell growth, division and differentiation...
September 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28864069/pthrp-is-essential-for-normal-morphogenetic-and-functional-development-of-the-murine-placenta
#17
Chloe Duval, Mark R Dilworth, Simon J Tunster, Susan J Kimber, Jocelyn D Glazier
No abstract text is available yet for this article.
October 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28836858/investigational-anabolic-agents-for-the-treatment-of-osteoporosis-an-update-on-recent-developments
#18
REVIEW
Anastasia D Dede, Polyzois Makras, Athanasios D Anastasilakis
Teriparatide, a PTH analogue, was the first anabolic agent to be approved for the treatment of osteoporosis in 2002. Abaloparatide was also recently approved by the FDA. The need for other anabolic agents is still unmet. Areas covered: In this review, we discuss target molecules and recent advances in the field of anabolic therapy for osteoporosis. PTH and PTHrP analogues binding to the PTH receptor and different routes of administration of teriparatide to avoid the burden of daily subcutaneous injections are discussed...
October 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28751994/hypercalcemia-in-lung-cancer-due-to-simultaneously-elevated-pthrp-and-ectopic-calcitriol-production-first-case-report
#19
Saed Nemr, Sunitha Alluri, Dhivya Sundaramurthy, Daniel Landry, Gregory Braden
Calcitriol-mediated hypercalcemia has been reported in malignant lymphomas and granulomatous diseases but not in lung carcinoma. We describe a patient with squamous cell lung carcinoma with hypercalcemia and elevated calcitriol levels. A 60-year-old Caucasian male patient with stage IIIB squamous cell lung cancer developed hypercalcemia at 14.8 mg/dL two years after receiving chemotherapy and radiotherapy where labs showed a serum intact PTH: 7 pg/mL, PTHrP: 30 pmol/L, 1,25-hydroxyvitamin D (calcitriol): 76 pg/mL, and 25-hydroxyvitamin D levels: <4 ng/mL...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/28743854/-new-methods-for-the-evaluation-of-bone-quality-bone-anabolic-agents-and-bone-quality
#20
Norio Yamamoto, Hiroyuki Tsuchiya
Teriparatide(TPTD)products that can be used clinically in Japan include a daily subcutaneous injection form produced by genetic engineering and a weekly subcutaneous injectable TPTD acetate form produced by chemical synthesis. Published reports indicate that both forms exhibit excellent antifracture efficacy, and as the only anabolic agents that promote osteogenesis, TPTD products now occupy a prominent position. However, the two forms differ considerably, not only in frequency of administration, but also in mechanism of action...
2017: Clinical Calcium
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