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https://www.readbyqxmd.com/read/28432788/structure-of-fam20a-reveals-a-pseudokinase-featuring-unique-disulfide-pattern-and-inverted-atp-binding
#1
Jixin Cui, Qinyu Zhu, Hui Zhang, Michael A Cianfrocco, Andres E Leschziner, Jack E Dixon, Junyu Xiao
Mutations in FAM20A cause tooth enamel defects known as Amelogenesis Imperfecta (AI) and renal calcification. We previously showed that Fam20A is a secretory pathway pseudokinase and allosterically activates the physiological casein kinase Fam20C to phosphorylate secreted proteins important for biomineralization (Cui et al., 2015). Here we report the nucleotide-free and ATP-bound structures of Fam20A. Fam20A exhibits a distinct disulfide bond pattern mediated by a unique insertion region. Loss of this insertion due to abnormal mRNA splicing interferes with the structure and function of Fam20A, resulting in AI...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28432640/osteoporosis-bone-mineral-density-and-ckd-mbd-treatment-considerations
#2
REVIEW
Jordi Bover, Lucía Bailone, Víctor López-Báez, Silvia Benito, Paola Ciceri, Andrea Galassi, Mario Cozzolino
Osteoporosis and chronic kidney disease (CKD) have both independently important potential impact on bone health. A significant number of patients with CKD stages 3a-5D have been shown to have low bone mineral density (BMD), leading to a strikingly elevated risk of fractures (mainly hip fractures) and higher associated morbidity and mortality. Mechanical properties of bone beyond age and menopausal status are additionally affected by intrinsic uremic factors. Therefore, we review in this article not only general concepts of osteoporosis and related consequences, but also the diagnostic and therapeutic implications of low BMD and bone fractures in CKD, beyond increased vascular calcification...
April 21, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28432604/phosphate-imbalance-in-patients-with-heart-failure
#3
REVIEW
E C Christopoulou, T D Filippatos, E Megapanou, M S Elisaf, G Liamis
Patients with heart failure often exhibit electrolyte abnormalities, such as hyponatremia or hypokalemia/hyperkalemia. Although not as common as the other electrolyte disturbances observed in patients with heart failure, phosphate imbalance is also of high importance in this population. The aim of this review is to present the mechanisms of low or high phosphate serum levels in patients with heart failure and its role in the pathogenesis and progression of heart dysfunction. Hypophosphatemia in patients with heart failure may be the result of co-existing electrolyte and acid-base abnormalities, pharmacological treatments, decreased intestinal absorption or secondary to sympathetic nervous system activation and co-morbidities, such as diabetes mellitus or heavy alcohol consumption...
April 22, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/28432595/what-animal-models-have-taught-us-about-the-safety-and-efficacy-of-bisphosphonates-in-chronic-kidney-disease
#4
REVIEW
Matthew R Allen, Mohammad W Aref
PURPOSE OF REVIEW: Bisphosphonates (BPs) have long been the gold-standard anti-remodeling treatment for numerous metabolic bone diseases. Since these drugs are excreted unmetabolized through the kidney, they are not recommended for individuals with compromised kidney function due to concerns of kidney and bone toxicity. The goal of this paper is to summarize the preclinical BP work in models of kidney disease with particular focus on the bone, kidney, and vasculature. RECENT FINDINGS: Summative data exists showing positive effects on bone and vascular calcifications with minimal evidence for bone or kidney toxicity in animal models...
April 21, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28432452/fluorescent-angioscopic-imaging-of-calcium-phosphate-tribasic-precursor-of-hydroxyapatite-the-major-calcium-deposit-in-human-coronary-plaques
#5
Takanobu Kobayashi, Osamu Nakagawa, Seiichiro Shirai, Ei Shimoyama, Nobuyuki Hiruta, Yasumi Uchida
Coronary calcification is a risk factor for ischemic heart disease. Hydroxyapatite that is formed by polymerization from calcium phosphate tribasic (CPT) is the major constituent of coronary calcium deposits. If CPT could be visualized, coronary calcification could be predicted and prevented. We discovered that when CPT and collagen I, the main constituent of collagen fibers, are mixed with lac dye (LD) and then exposed to fluorescent light excited at 345 ± 15 nm and emitted at 420 nm, a purple fluorescence that is characteristic of CPT only is elicited...
April 21, 2017: International Journal of Cardiovascular Imaging
https://www.readbyqxmd.com/read/28431773/atypical-moyamoya-syndrome-with-brain-calcification-and-stenosis-of-abdominal-aorta-and-renal-arteries
#6
Hideki Uchikawa, Katsunori Fujii, Mayuko Fujita, Tomoko Okunushi, Naoki Shimojo
Moyamoya syndrome is a progressive cerebrovascular disease that is characterized by stenosis of the terminal portion of the internal carotid artery and its main branches, in combination with an accompanying disease. We herein describe an 8-year-old boy exhibiting transient loss of consciousness, who had recurrent seizures in infancy with progressive brain calcification. On admission, he was alert but magnetic resonance angiography showed bilateral stenosis of the whole internal carotid artery and proliferation of vascular collaterals, and brain CT revealed calcification on bilateral putamen...
April 18, 2017: Brain & Development
https://www.readbyqxmd.com/read/28431628/clinical-and-quantitative-analysis-of-patients-with-crowned-dens-syndrome
#7
Teruyuki Takahashi, Masato Tamura, Toshiaki Takasu, Satoshi Kamei
BACKGROUND: Crowned dens syndrome (CDS) is a radioclinical entity defined by calcium deposition on the transverse ligament of atlas (TLA). In this study, the novel semi-quantitative diagnostic criteria for CDS to evaluate the degree of calcification on TLA by cervical CT are proposed. METHOD: From January 2010 to September 2014, 35 patients who were diagnosed with CDS by cervical CT were adopted as subjects in this study. Based on novel criteria, calcium deposition on TLA was classified into "Stage" and "Grade", to make a score, which was evaluated semi-quantitatively...
May 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28431214/interferon-%C3%AE-released-by-activated-cd8-t-lymphocytes-impairs-the-calcium-resorption-potential-of-osteoclasts-in-calcified-human-aortic-valves
#8
Edit Nagy, Yang Lei, Eduardo Martínez-Martínez, Simon C Body, Florian Schlotter, Michael Creager, Alexander Assmann, Kamal Khabbaz, Peter Libby, Göran K Hansson, Elena Aikawa
Calcium content in patients with calcific aortic valve disease (CAVD) correlates with the severity of stenosis. In CAVD, activated T lymphocytes localize with osteoclast regions; however, the functional consequences of this association remain unknown. We hypothesized that CD8(+) T cells modulate calcification in CAVD. Explanted CAVD valves (n = 52) dissected into noncalcified and calcified portions were subjected to mRNA extraction, real-time quantitative PCR, enzyme-linked immunosorbent assay, and immunohistochemical analyses...
April 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28430540/demystifying-orbital-emergencies-a-pictorial-review
#9
Viet D Nguyen, Achint K Singh, Wilson B Altmeyer, Bundhit Tantiwongkosi
Imaging of the orbit plays an important role in the workup of orbital emergencies. Orbital imaging is particularly useful in the emergency department, where clinical history and physical examination may be limited or delayed until the exclusion or treatment of more life-threatening conditions. Cross-sectional orbital imaging with multidetector computed tomography (CT) and magnetic resonance (MR) imaging is commonly performed in addition to ultrasonography. In an emergent setting, CT is the preferred modality when evaluating for intraorbital foreign bodies, fractures, or calcifications within a mass lesion...
April 21, 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/28430186/independence-of-nutrient-limitation-and-carbon-dioxide-impacts-on-the-southern-ocean-coccolithophore-emiliania-huxleyi
#10
Marius N Müller, Thomas W Trull, Gustaaf M Hallegraeff
Future oceanic conditions induced by anthropogenic greenhouse gas emissions include warming, acidification and reduced nutrient supply due to increased stratification. Some parts of the Southern Ocean are expected to show rapid changes, especially for carbonate mineral saturation. Here we compare the physiological response of the model coccolithophore Emiliania huxleyi (strain EHSO 5.14, originating from 50(o)S, 149(o)E) with pH/CO2 gradients (mimicking ocean acidification ranging from 1 to 4 × current pCO2 levels) under nutrient-limited (nitrogen and phosphorus) and -replete conditions...
April 21, 2017: ISME Journal
https://www.readbyqxmd.com/read/28429560/is-there-a-role-for-newer-biomarkers-in-chronic-kidney-disease-mineral-and-bone-disorder-management
#11
Sven-Jean Tan, Michael Mx Cai
The current management of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) relies largely on clinical judgement and assessment of biochemical parameters including serum calcium, phosphate and intact parathyroid hormone concentrations. In the past two decades, there has been a leap in the understanding of the pathophysiology of CKD-MBD, leading to the discovery of novel biomarkers. The potential utility of these markers in this clinical setting is an area of intense investigation. In the absence of any guidelines aiding the clinician's understanding and application of these markers, we summarise the current available literature surrounding fibroblast growth factor-23, α-Klotho, sclerostin and serum calcification propensity testing and their respective assays in the context of CKD-MBD management...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28429551/the-role-of-calcium-and-non-calcium-based-phosphate-binders-in-chronic-kidney-disease
#12
Grahame J Elder, Jacqueline Center
Rising levels of serum phosphate occur late in the course of chronic kidney disease (CKD) and have been easy targets for nephrologists to treat using phosphate binding drugs, as well as fertile ground for the pharmaceutical industry, for meta-analysis and for the earnest pontifications of guideline writers. Unfortunately, the evidence does little to support this focus, which might be better applied to earlier, adaptive hormonal changes, and to phosphate balance rather than serum phosphate levels. Nevertheless, phosphate binders are ubiquitously prescribed to patients on dialysis, and often prescribed to patients with earlier stages of CKD; for which there is no evidence of benefit and some evidence that calcium-based binders (CBBs) and possibly non-CBBs may cause more harm than placebo...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28429550/parathyroid-hormone-targets-in-chronic-kidney-disease-and-managing-severe-hyperparathyroidism
#13
Carmel M Hawley, Stephen G Holt
Appropriate targets for parathyroid hormone (PTH) in patients with chronic kidney disease (CKD) stages 3-5D are controversial, as are the means by which these targets might be achieved. Secondary hyperparathyroidism is linked to symptoms like bone pain and itch, in addition to less clinically overt issues like bone fragility as well as vascular and soft tissue calcification which may lead to adverse hard endpoints, particularly fracture and death. Recognized therapies for managing a rising PTH include vitamin D analogues, with or without calcimimetic (where available), in addition to management of serum mineral concentrations with diet, binders and dialysis...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28429548/is-serum-phosphate-a-useful-target-in-patients-with-chronic-kidney-disease-and-what-is-the-role-for-dietary-phosphate-restriction
#14
Nigel D Toussaint, Stephen G Holt
A complex system of endocrine and paracrine signals exists to control phosphate balance. Dysregulation of these systems in patients with chronic kidney disease has serious clinical consequences. Whilst observational studies have shown associations between higher serum phosphate levels and poor clinical outcomes, the direction of causality has not been demonstrated. Whether there is a target level of serum phosphate remains controversial and no randomized trials to date have proved that strategies to lower extracellular phosphate actually improve clinical outcomes...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28429547/the-use-of-bone-turnover-markers-in-chronic-kidney-disease-mineral-and-bone-disorders
#15
Cherie Chiang
Bone turnover markers assist in fracture risk prediction, management and monitoring of osteoporosis in patients without chronic kidney disease (CKD). The use in CKD-mineral bone disorder (MBD) has been limited as many of these markers and breakdown products are renally excreted, including the most commonly used and well standardized procollagen type I N propeptide and C-terminal cross-linking telopeptide of type I collagen. Of the markers unaffected by renal function, bone specific alkaline phosphatase is associated with mortality and fracture rate in CKD subjects and is now available on several automated analysers...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28429546/should-nephrologists-consider-vascular-calcification-screening
#16
Rathika Krishnasamy, Eugenie Pedagogos
Vascular calcification (VC) has been widely discussed over the last few decades and is associated with significant morbidity and mortality among patients with chronic kidney disease. Importantly, these patients have premature and rapidly progressive calcification when compared with the general population. VC is an active and complex process that is closely regulated by a growing list of inducers and inhibitors. VC can be detected using several non-invasive modalities including plain radiography, echocardiogram and computed tomography scans...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28429336/effects-of-a-curcumin-based-supplementation-in-asymptomatic-subjects-with-low-bone-density-a-preliminary-24-week-supplement-study
#17
A Riva, S Togni, L Giacomelli, F Franceschi, R Eggenhoffner, B Feragalli, G Belcaro, M Cacchio, H Shu, M Dugall
OBJECTIVE: Osteopenia is a chronic bone condition characterized by decreased calcification, density, or bone mass that, if untreated, can lead to osteoporosis and bone fractures. Although its increasing prevalence, nowadays osteopenia is not adequately prevented and managed. In this study, we evaluated the efficacy, in term of changes in bone density, and safety of an oral formulation based on turmeric phytosome (Meriva®), in subjects suffering from low bone density. PATIENTS AND METHODS: 57 otherwise healthy subjects with low bone density were enrolled in this pilot, supplement study...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28429221/associations-of-osteocalcin-osteoprotegerin-and-calcitonin-with-inflammation-biomarkers-in-atherosclerotic-plaques-of-coronary-arteries
#18
Ya V Polonskaya, E V Kashtanova, I S Murashov, A M Volkov, A V Kurguzov, A M Chernyavsky, Yu I Ragino
We studied associations of osteocalcin, osteoprotegerin, and calcitonin with markers of inflammation in atherosclerotic plaques in coronary arteries and assessed the influence of these biomolecules on calcification of atherosclerotic plaques. The initial stage of calcification of atherosclerotic plaques is characterized by activation of inflammatory processes, which is seen from increased levels of proinflammatory biomarkers (IL-6, IL 8, TNF-α, and IL-1β). Progressive calcification of atherosclerotic plaques is accompanied by insignificant accumulation of calcitonin and osteoprotegerin...
April 21, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28428650/routine-mammography-an-opportunity-for-the-diagnosis-of-chronic-degenerative-diseases-a-cross-sectional-study
#19
Flávio Augusto Teixeira Ronzani, Filomena Maria Kirchmaier, Nathália Mussi Monteze, Edson José de Carvalho Magacho, Marcus Gomes Bastos, Natália Maria da Silva Fernandes
OBJECTIVE: The aim of this study was to evaluate breast arterial calcification (BAC) detected on routine mammography, analyzing its association with chronic degenerative disease. MATERIALS AND METHODS: This was a cross-sectional study involving women treated at a specialized outpatient clinic for high-risk hypertension, diabetes, or chronic kidney disease, as well as volunteers who participated in a study to validate a method of screening for occult renal disease...
March 2017: Radiologia Brasileira
https://www.readbyqxmd.com/read/28428481/serum-tartrate-resistant-acid-phosphatase-5b-levels-are-associated-with-the-severity-and-extent-of-coronary-atherosclerosis-in-patients-with-coronary-artery-disease
#20
Taichirou Morisawa, Akihiro Nakagomi, Keiichi Kohashi, Yoshiki Kusama, Wataru Shimizu
AIMS: Tartrate-resistant acid phosphatase (TRACP)-5b and osteoprotegerin (OPG) are specific and sensitive markers of bone resorption in patients with rheumatoid arthritis (RA) and chronic kidney disease (CKD). The TRACP-5b level is associated with the severity of RA and CKD, while the OPG level is associated with the severity of coronary atherosclerosis and calcification, and can predict a poor outcome in patients with coronary artery disease (CAD). However, the impact of TRACP-5b on coronary atherosclerosis in CAD patients remains unclear...
April 19, 2017: Journal of Atherosclerosis and Thrombosis
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