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https://www.readbyqxmd.com/read/28548993/muscle-metabolism
#1
Nicolas Tardif, Jonathan Grip, Olav Rooyackers
PURPOSE OF REVIEW: To review the recent findings on metabolic derangements leading to loss of muscle mass and function. RECENT FINDINGS: Several recent studies investigated methods to assess muscle mass and function and its clinical relevance. These are also included. A few studies confirm that a low muscle mass is related to a worse outcome but also a compromised muscle function at discharge is related to long-term survival. A low quality of muscle assessed by the density of muscle from a computed tomography scan is related to mortality...
May 25, 2017: Current Opinion in Critical Care
https://www.readbyqxmd.com/read/28537214/pharmacokinetic-drug-evaluation-of-safinamide-mesylate-for-the-treatment-of-mid-to-late-stage-parkinson-s-disease
#2
Thomas Müller
Patients with Parkinson's disease suffer from a heterogeneous expression of neurotransmitter deficits. They cause an individual variable expression of motor and non-motor symptoms. Thus, drugs with various mechanisms of actions are suitable to counteract these disease related neurotransmitter alterations. Areas covered: This invited review suggests safinamide as an ideal compound for therapy of Parkinson's disease, as its pharmacological profile includes reversible monoamine oxidase B inhibition, blockage of voltage-dependent sodium channels, modulation of calcium channels and abnormal glutamate release...
June 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28536695/cardiac-protection-of-valsartan-on-juvenile-rats-with-heart-failure-by-inhibiting-activity-of-camkii-via-attenuating-phosphorylation
#3
Yao Wu, Feifei Si, Xiaojuan Ji, Kunfeng Jiang, Sijie Song, Qijian Yi
Background. This study was undertaken to determine relative contributions of phosphorylation and oxidation to the increased activity of calcium/calmodulin-stimulated protein kinase II (CaMKII) in juveniles with cardiac myocyte dysfunction due to increased pressure overload. Methods. Juvenile rats underwent abdominal aortic constriction to induce heart failure. Four weeks after surgery, rats were then randomly divided into two groups: one group given valsartan (HF + Val) and the other group given placebo (HF + PBO)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28534087/interspecies-differences-in-pth-mediated-pka-phosphorylation-of-the-epithelial-calcium-channel-trpv5
#4
Mark K van Goor, Sjoerd Verkaart, Teunis J van Dam, Martijn A Huynen, Jenny van der Wijst
The epithelial calcium (Ca(2+)) channel TRPV5 (transient receptor potential vanilloid 5) is expressed in the distal convoluted tubule of the kidney and facilitates active Ca(2+) reabsorption. This process is instrumental for the maintenance of Ca(2+) homeostasis. Therefore, all aspects of TRPV5 function are tightly regulated by the calciotropic parathyroid hormone (PTH). Rabbit (rb)TRPV5 channel activity was shown to be stimulated upon PTH-mediated protein kinase A (PKA) phosphorylation. Since there is incomplete conservation of the PKA consensus motif (RR/QxT) across species, the aim of this study was to extend these findings to humans and characterize the expression and function of human (h)TRPV5...
May 22, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28528667/genetically-encoded-calcium-indicators-as-probes-to-assess-the-role-of-calcium-channels-in-disease-and-for-high-throughput-drug-discovery
#5
John J Bassett, Gregory R Monteith
The calcium ion (Ca(2+)) is an important signaling molecule implicated in many cellular processes, and the remodeling of Ca(2+) homeostasis is a feature of a variety of pathologies. Typical methods to assess Ca(2+) signaling in cells often employ small molecule fluorescent dyes, which are sometimes poorly suited to certain applications such as assessment of cellular processes, which occur over long periods (hours or days) or in vivo experiments. Genetically encoded calcium indicators are a set of tools available for the measurement of Ca(2+) changes in the cytosol and subcellular compartments, which circumvent some of the inherent limitations of small molecule Ca(2+) probes...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28527222/functional-characterization-of-c-terminal-ryanodine-receptor-1-variants-associated-with-central-core-disease-or-malignant-hyperthermia
#6
Remai Parker, Anja H Schiemann, Elaine Langton, Terasa Bulger, Neil Pollock, Andrew Bjorksten, Robyn Gillies, David Hutchinson, Richard Roxburgh, Kathryn M Stowell
BACKGROUND: Central core disease and malignant hyperthermia are human disorders of skeletal muscle resulting from aberrant Ca2+ handling. Most malignant hyperthermia and central core disease cases are associated with amino acid changes in the type 1 ryanodine receptor (RyR1), the skeletal muscle Ca2+-release channel. Malignant hyperthermia exhibits a gain-of-function phenotype, and central core disease results from loss of channel function. For a variant to be classified as pathogenic, functional studies must demonstrate a correlation with the pathophysiology of malignant hyperthermia or central core disease...
May 15, 2017: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/28527192/in-vitro-evaluation-of-an-injectable-biphasic-calcium-phosphate-bcp-carrier-system-combined-with-recombinant-human-bone-morphogenetic-protein-rhbmp-9
#7
Masako Fujioka-Kobayashi, Benoit Schaller, Yufeng Zhang, Benjamin E Pippenger, Richard J Miron
Bone morphogenetic protein 9 (BMP9) has previously been characterized as the strongest osteoinductive growth factor among the BMP family. The aim of the present study was to evaluate the possibility of combining rhBMP9 with an injectable biphasic calcium phosphate (I-BCP, maxresorb inject®), since I-BCP is an easy to handle biomaterial with ideal properties for bone augmentation procedures. The adsorption potential of rhBMP9 as well as the cell behavior of bone stromal ST2 cells were investigated on cell viability, adhesion, proliferation and osteogenic differentiation for I-BCP combined with/without rhBMP9 in vitro...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28527013/central-activation-metabolites-and-calcium-handling-during-fatigue-with-repeated-maximal-isometric-contractions-in-human-muscle
#8
Simeon P Cairns, Luke A G Inman, Caroline P MacManus, Ingrid G L van de Port, Patricia A Ruell, Jeanette M Thom, Martin W Thompson
PURPOSE: To determine the roles of calcium (Ca(2+)) handling by sarcoplasmic reticulum (SR) and central activation impairment (i.e., central fatigue) during fatigue with repeated maximal voluntary isometric contractions (MVC) in human muscles. METHODS: Contractile performance was assessed during 3 min of repeated MVCs (7-s contraction, 3-s rest, n = 17). In ten participants, in vitro SR Ca(2+)-handling, metabolites, and fibre-type composition were quantified in biopsy samples from quadriceps muscle, along with plasma venous [K(+)]...
May 19, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28522367/qrs-t-wave-and-calcium-alternans-in-a-type-i-diabetic-mouse-model-for-spontaneous-post-myocardial-infarction-ventricular-tachycardia-a-mechanism-for-the-antiarrhythmic-effect-of-statins
#9
Hongwei Jin, Charles M Welzig, Mark Aronovitz, Farzad Noubary, Robert Blanton, Bo Wang, Mohammad Rajab, Alfred Albano, Mark S Link, Sami F Noujaim, Ho-Jin Park, Jonas B Galper
BACKGROUND: The incidence of sudden arrhythmic death is markedly increased in diabetics. OBJECTIVE: Develop a mouse model for Post MI VT in the diabetic heart and determine the mechanism of an antiarrhythmic effect of statins. METHODS: EKG transmitters were implanted in wild type (WT), placebo and pravastatin treated Type I diabetic Akita mice, MIs induced by coronary ligation, Ca(2+) transients studied by optical mapping, Ca(2+) transients and sparks in left VM (VM) by the Ionoptix system and confocal microscopy...
May 15, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28522248/adverse-effects-in-kidney-function-antioxidant-systems-and-histopathology-in-rats-receiving-monosodium-glutamate-diet
#10
María Del Carmen Contini, Ana Fabro, Néstor Millen, Adriana Benmelej, Stella Mahieu
We investigated the effects of adding of monosodium glutamate (MSG) to a standard diet on oxidative stress in kidney, nitric oxide excretion, renal ions handling and blood pressure. We examined the association of these changes with the effects on renal histology. The study was performed on male Wistar rats (5 weeks old) divided into 3 groups: 1) MSG group were fed a diet supplemented with 3g of MSG/kg b.w./day, five days a week, and spontaneous ingestion of a 1% MSG solution during 16 weeks; 2) NaCl group were fed a diet with NaCl (1g/kg b...
May 15, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28509762/beetroot-juice-increases-human-muscle-force-without-changing-ca2-handling-proteins
#11
Jamie Whitfield, Daniel Gamu, George J F Heigenhauser, Luc J C van Loon, Lawrence L Spriet, A Russell Tupling, Graham P Holloway
Dietary inorganic nitrate (NO3) supplementation improves skeletal muscle (SkM) contractile efficiency, and while rodent literature has suggested improvements in calcium handling or redox modifications as likely explanations, the direct mechanism-of-action in humans remains unknown. PURPOSE: To examine the effects of 7-d of beetroot juice (BRJ) supplementation on SkM contractile characteristics and function. METHODS: Recreationally active males (n=8) underwent transcutaneous electrical muscle stimulation of the vastus lateralis for evaluation of contractile characteristics before (pre) and after (post) 7-d of BRJ supplementation (280 mL/day, ~26 mmol NO3)...
May 15, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28497395/cardio-protective-effects-of-qishen-granule-on-sarcoplasmic-reticulum-ca-2-handling-in-heart-failure-rats
#12
Ling-Hui Lu, Chun Li, Qi-Yan Wang, Qian Zhang, Yi Zhang, Hui Meng, Yong Wang, Wei Wang
OBJECTIVES: To assess the effects of Qishen Granule (, QSG) on sarcoplasmic reticulum (SR) Ca(2+) handling in heart failure (HF) model of rats and to explore the underlying molecular mechanisms. METHODS: HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham (n=10), model (n=10), QSG (n=12, 2.2 g/kg daily) and metoprolol groups (n=12, 10.5 mg/kg daily). The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing...
May 11, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28487987/g-protein-phosphorylated-gata4-and-vegf-expression-in-the-hearts-of-transgenic-mice-overexpressing-%C3%AE-1-and-%C3%AE-2-adrenergic-receptors
#13
Hyun-Jin Tae, Natalia Petrashevskaya, In Hye Kim, Joon Ha Park, Jae-Chul Lee, Moo-Ho Won, Yang Hee Kim, Ji Hyeon Ahn, Jinseu Park, Soo Young Choi, Yong Hwan Jeon
β1- and β2-adrenergic receptors (ARs) regulate cardiac contractility, calcium handling and protein phosphorylation. The present study aimed to examine the expression levels of vascular endothelial growth factor A (VEGF‑A) and several G proteins, and the phosphorylation of transcription factor GATA binding protein 4 (GATA4), by western blot analysis, using isolated hearts from 6 month‑old transgenic (TG) mice that overexpress β1AR or β2AR. Cardiac contractility/relaxation and heart rate was increased in both β1AR TG and β2AR TG mouse hearts compared with wild type; however, no significant differences were observed between the β1‑ and β2AR TG mouse hearts...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28482850/mutant-tdp-43-does-not-impair-mitochondrial-bioenergetics-in-vitro-and-in-vivo
#14
Hibiki Kawamata, Pablo Peixoto, Csaba Konrad, Gloria Palomo, Kirsten Bredvik, Meri Gerges, Federica Valsecchi, Leonard Petrucelli, John M Ravits, Anatoly Starkov, Giovanni Manfredi
BACKGROUND: Mitochondrial dysfunction has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Functional studies of mitochondrial bioenergetics have focused mostly on superoxide dismutase 1 (SOD1) mutants, and showed that mutant human SOD1 impairs mitochondrial oxidative phosphorylation, calcium homeostasis, and dynamics. However, recent reports have indicated that alterations in transactivation response element DNA-binding protein 43 (TDP-43) can also lead to defects of mitochondrial morphology and dynamics...
May 8, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28473749/amyloid-%C3%AE-exposed-human-astrocytes-overproduce-phospho-tau-and-overrelease-it-within-exosomes-effects-suppressed-by-calcilytic-nps-2143-further-implications-for-alzheimer-s-therapy
#15
Anna Chiarini, Ubaldo Armato, Emanuela Gardenal, Li Gui, Ilaria Dal Prà
The two main drivers of Alzheimer's disease (AD), amyloid-β (Aβ) and hyperphosphorylated Tau (p-Tau) oligomers, cooperatively accelerate AD progression, but a hot debate is still ongoing about which of the two appears first. Here we present preliminary evidence showing that Tau and p-Tau are expressed by untransformed cortical adult human astrocytes in culture and that exposure of such cells to an Aβ42 proxy, Aβ25-35, which binds the calcium-sensing receptor (CaSR) and activates its signaling, significantly increases intracellular p-Tau levels, an effect CaSR antagonist (calcilytic) NPS 2143 wholly hinders...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28469494/studying-dyadic-structure-function-relationships-a-review-of-current-modeling-approaches-and-new-insights-into-ca-2-mis-handling
#16
Mary M Maleckar, Andrew G Edwards, William E Louch, Glenn T Lines
Excitation-contraction coupling in cardiac myocytes requires calcium influx through L-type calcium channels in the sarcolemma, which gates calcium release through sarcoplasmic reticulum ryanodine receptors in a process known as calcium-induced calcium release, producing a myoplasmic calcium transient and enabling cardiomyocyte contraction. The spatio-temporal dynamics of calcium release, buffering, and reuptake into the sarcoplasmic reticulum play a central role in excitation-contraction coupling in both normal and diseased cardiac myocytes...
2017: Clinical Medicine Insights. Cardiology
https://www.readbyqxmd.com/read/28461171/connecting-mitochondrial-dynamics-and-life-or-death-events-via-bcl-2-family-proteins
#17
REVIEW
Abdel Aouacheria, Stephen Baghdiguian, Heather M Lamb, Jason D Huska, Fernando J Pineda, J Marie Hardwick
The morphology of a population of mitochondria is the result of several interacting dynamical phenomena, including fission, fusion, movement, elimination and biogenesis. Each of these phenomena is controlled by underlying molecular machinery, and when defective can cause disease. New understanding of the relationships between form and function of mitochondria in health and disease is beginning to be unraveled on several fronts. Studies in mammals and model organisms have revealed that mitochondrial morphology, dynamics and function appear to be subject to regulation by the same proteins that regulate apoptotic cell death...
April 28, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28455288/cardiac-myofibrillar-contractile-properties-during-the-progression-from-hypertension-to-decompensated-heart-failure
#18
Laurin M Hanft, Craig A Emter, Kerry S McDonald
Heart failure arises, in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, calcium handling, and myofibrillar function. However, little is known about the changes in myofibrillar contractile properties during the progression from hypertension to decompensated heart failure. The aim of this study was to provide a comprehensive assessment of myofibrillar functional properties from health to heart disease. A rodent model of uncontrolled hypertension was used to test the hypothesis that myocytes in compensated hearts exhibit increased force, higher rates of force development, faster loaded shortening, and greater power output; however, with progression to overt heart failure we predicted marked depression in these contractile properties...
April 28, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28439258/diabetic-cardiomyopathy-an-immunometabolic-perspective
#19
REVIEW
Paras K Mishra, Wei Ying, Shyam Sundar Nandi, Gautam K Bandyopadhyay, Kaushik K Patel, Sushil K Mahata
The heart possesses a remarkable inherent capability to adapt itself to a wide array of genetic and extrinsic factors to maintain contractile function. Failure to sustain its compensatory responses results in cardiac dysfunction, leading to cardiomyopathy. Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction in the absence of hypertension and coronary artery disease. Changes in substrate metabolism, oxidative stress, endoplasmic reticulum stress, formation of extracellular matrix proteins, and advanced glycation end products constitute the early stage in DCM...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28426939/high-throughput-agonist-shift-assay-development-for-the-analysis-of-m1-positive-allosteric-modulators
#20
Michelle F Homsher, Douglas C Beshore, Jason Cassaday, Brian Squadroni, Elizabeth Mohammed, Michelle Hartnett, Stephen Day, Lei Ma, David Pechter, Michelle D Smith, Fredrick Monsma, Paul Zuck, Michael F Finley, Victor N Uebele, Jeffrey D Hermes
Agonist shift assays feature cross-titrations of allosteric modulators and orthosteric ligands. Information generated in agonist shift assays can include a modulator's effect on the orthosteric agonist's potency (alpha) and efficacy (beta), as well as direct agonist activity of the allosteric ligand (tauB) and the intrinsic binding affinity of the modulator to the unoccupied receptor (KB). Because of the heavy resource demand and complex data handling, these allosteric parameters are determined infrequently during the course of a drug discovery program and on a relatively small subset of compounds...
April 1, 2017: SLAS Discovery
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