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https://www.readbyqxmd.com/read/28322744/basal-ryanodine-receptor-activity-suppresses-autophagic-flux
#1
Tim Vervliet, Isabel Pintelon, Kirsten Welkenhuyzen, Martin D Bootman, Hiroko Bannai, Katsuhiko Mikoshiba, Wim Martinet, Nael Nadif Kasri, Jan B Parys, Geert Bultynck
The inositol 1,4,5-trisphosphate receptors (IP3Rs) and intracellular Ca(2+) signaling are critically involved in regulating different steps of autophagy, a lysosomal degradation pathway. The ryanodine receptors (RyR), intracellular Ca(2+)-release channels mainly expressed in excitable cell types including muscle and neurons, have however not yet been extensively studied in relation to autophagy. Yet, aberrant expression and excessive activity of RyRs in these tissues has been implicated in the onset of several diseases including Alzheimer's disease, where impaired autophagy regulation contributes to the pathology...
March 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28316073/arrhythmic-effects-of-epac-mediated-ryanodine-receptor-activation-in-langendorff-perfused-murine-hearts-are-associated-with-reduced-conduction-velocity
#2
Mengye Li, Sandeep Hothi, Samantha C Salvage, Kamalan Jeevaratnam, Andrew A Grace, Christopher L-H Huang
Recent papers have attributed arrhythmic substrate in murine RyR2-P2328S hearts to reduced action potential (AP) conduction velocities (CV), reflecting acute functional inhibition and/or reduced expression of sodium channels. We explored for acute effects of direct Epac (exchange protein directly activated by cAMP)-mediated ryanodine receptor-2 (RyR2) activation on arrhythmic substrate and CV. Monophasic action potential recordings demonstrated that initial steady (8-Hz) extrinsic pacing elicited ventricular tachycardia (VT) in 0 of 18 Langendorff-perfused wild-type mouse ventricles before pharmacological intervention...
March 18, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28298333/multiple-ampk-activators-inhibit-l-carnitine-uptake-in-c2c12-skeletal-muscle-myotubes
#3
Andy Shaw, Stewart Jeromson, Kenneth R Watterson, John D Pediani, Iain Gallagher, Tim Whalley, Gillian Dreczkowski, Naomi Brooks, Stuart Galloway, D Lee Hamilton
Mutations in the gene that encodes the principal L-Carnitine transporter, OCTN2, can lead to a reduced intracellular L-Carnitine pool and the disease Primary Carnitine Deficiency. L-Carnitine supplementation is used therapeutically to increase intracellular L-Carnitine. As AMPK and insulin regulate fat metabolism and substrate uptake we hypothesised that AMPK activating compounds and insulin would increase L-Carnitine uptake in C2C12 myotubes. The cells express all three OCTN transporters at the mRNA level and immunohistochemistry confirmed expression at the protein level...
March 15, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28292875/in-vivo-ca-2-dynamics-induced-by-ca-2-injection-in-individual-rat-skeletal-muscle-fibers
#4
Mario Wakizaka, Hiroaki Eshima, Yoshinori Tanaka, Hideki Shirakawa, David C Poole, Yutaka Kano
In contrast to cardiomyocytes, store overload-induced calcium ion (Ca(2+)) release (SOICR) is not considered to constitute a primary Ca(2+) releasing system from the sarcoplasmic reticulum (SR) in skeletal muscle myocytes. In the latter, voltage-induced Ca(2+) release (VICR) is regarded as the dominant mechanism facilitating contractions. Any role of the SOICR in the regulation of cytoplasmic Ca(2+) concentration ([Ca(2+)]i) and its dynamics in skeletal muscle in vivo remains poorly understood. By means of in vivo single fiber Ca(2+) microinjections combined with bioimaging techniques, we tested the hypothesis that the [Ca(2+)]i dynamics following Ca(2+) injection would be amplified and fiber contraction facilitated by SOICR...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28290972/malignant-hyperthermia-susceptibility-and-fitness-for-duty
#5
Michael A Lee, Erin B McGlinch, Maria C McGlinch, John F Capacchione
INTRODUCTION: Malignant hyperthermia (MH) is an inherited hypermetabolic condition characterized by uncontrolled calcium release from the sarcoplasmic reticulum of skeletal muscle, usually from exposure to inhaled general anesthetics and/or the depolarizing neuromuscular blocking agent succinylcholine. Multiple case reports now reveal that crises may be precipitated by environmental factors such as exercise or high ambient temperatures. Common signs of an MH crisis include life-threatening hyperthermia, metabolic acidosis, muscle rigidity, and tachycardia...
March 2017: Military Medicine
https://www.readbyqxmd.com/read/28272341/liver-effects-of-clinical-drugs-differentiated-in-human-liver-slices
#6
Alison E M Vickers, Anatoly V Ulyanov, Robyn L Fisher
Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM), diclofenac (DCF, 1 mM) and etomoxir (ETM, 100 μM). Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM) and cyclosporin A (CSA, 10 μM), while GSH was affected more than ATP by methimazole (MMI, 500 μM), terbinafine (TBF, 100 μM), and carbamazepine (CBZ 100 μM)...
March 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28272142/early-development-identification-of-mode-of-action-and-use-of-dantrolene-sodium-the-role-of-keith-ellis-ph-d
#7
Neil A Pollock, Roslyn G Machon, Henry Rosenberg
Dantrolene-a nitrofurantoin derivative-was developed by Snyder et al. in 1967. After initial discovery of its muscle relaxation potential, investigations in a number of species demonstrated dose-dependent reductions in skeletal muscle tone that were long lasting, relatively nontoxic, and free of adverse effects such as respiratory impairment. Ellis et al. then published a number of papers investigating the means by which dantrolene produced these effects. Using a series of classic physiologic models, Ellis investigated potential sites of action for the new drug, eventually narrowing this down to the intracellular calcium-release mechanism...
March 8, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28246924/jsa-guideline-for-the-management-of-malignant-hyperthermia-crisis-2016
#8
REVIEW
(no author information available yet)
Malignant hyperthermia (MH) can be fatal if the crisis is not appropriately treated. It is an inherited disease usually triggered by the administration of volatile inhalational anesthetics and/or succinylcholine, a muscle relaxant. In a patient with suspected MH, the mechanism of calcium release from storage in the sarcoplasmic reticulum in the skeletal muscle is abnormally accelerated. Unexplained hypercarbia representing >55 mmHg of end-tidal carbon dioxide, tachycardia, and muscle rigidity (including masseter muscle rigidity) are early signs of the initiation of MH, because the metabolism is accelerated...
February 28, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/28226201/genomewide-association-study-of-alcohol-dependence-identifies-risk-loci-altering-ethanol-response-behaviors-in-model-organisms
#9
Amy E Adkins, Laura M Hack, Tim B Bigdeli, Vernell S Williamson, G Omari McMichael, Mohammed Mamdani, Alexis Edwards, Fazil Aliev, Robin F Chan, Poonam Bhandari, Richard C Raabe, Joseph T Alaimo, GinaMari G Blackwell, Arden A Moscati, Ryan S Poland, Benjamin Rood, Diana G Patterson, Dermot Walsh, John B Whitfield, Gu Zhu, Grant W Montgomery, Anjali K Henders, Nicholas G Martin, Andrew C Heath, Pamela A F Madden, Josef Frank, Monika Ridinger, Norbert Wodarz, Michael Soyka, Peter Zill, Marcus Ising, Markus M Nöthen, Falk Kiefer, Marcella Rietschel, Joel Gelernter, Richard Sherva, Ryan Koesterer, Laura Almasy, Hongyu Zhao, Henry R Kranzler, Lindsay A Farrer, Brion S Maher, Carol A Prescott, Danielle M Dick, Silviu A Bacanu, Laura D Mathies, Andrew G Davies, Vladimir I Vladimirov, Mike Grotewiel, M Scott Bowers, Jill C Bettinger, Bradley T Webb, Michael F Miles, Kenneth S Kendler, Brien P Riley
BACKGROUND: Alcohol Dependence (AD) shows evidence for genetic liability, but genes influencing risk remain largely unidentified. METHODS: We conducted a genomewide association study in 706 related AD cases and 1748 unscreened population controls from Ireland. We sought replication in 15,496 samples of European descent. We used model organisms to assess the role of orthologous genes in ethanol response behaviors. We tested one primate-specific gene for expression differences in case/control post-mortem brain tissue...
February 22, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28209803/correlation-between-membrane-protein-concentrations-and-transcellular-transport-activity-for-breast-cancer-resistance-protein
#10
Houfu Liu, Liang Huang, Yi Li, Tingting Fu, Xueying Sun, Yan-Yan Zhang, Ruina Gao, Qingfang Chen, Wandong Zhang, Jasminder Sahi, Scott Summerfield, Kelly Dong
Emerging evidence indicates an important role for breast cancer resistance protein (BCRP) in limiting brain penetration of substrate drugs. While in vitro Transwell® assays can provide an indication of BCRP substrate potential, the predictability of these to in vivo brain penetration is still under debate. The present study examines the correlation of BCRP protein concentration and transcellular transport activity across MDCKII monolayers. We expressed human BCRP or murine Bcrp1 in MDCKII wild-type cells using BacMam2 virus transduction...
February 16, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28181698/calcium-uptake-via-mitochondrial-uniporter-contributes-to-palmitic-acid-induced-apoptosis-in-mouse-podocytes
#11
Zeting Yuan, Aili Cao, Hua Liu, Henjiang Guo, Yingjun Zang, Yi Wang, Yunman Wang, Hao Wang, Peihao Yin, Wen Peng
Podocytes are component cells of the glomerular filtration barrier, and their loss by apoptosis is the main cause of proteinuria that leads to diabetic nephropathy (DN). Therefore, insights into podocyte apoptosis mechanism would allow a better understanding of DN pathogenesis and thus help develop adequate therapeutic strategies. Here, we investigated the molecular mechanism of palmitic acid-inhibited cell death in mouse podocytes, and found that palmitic acid increased cell death in a dose- and time-dependent manner...
February 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28166109/whether-to-proceed-with-deep-brain-stimulator-battery-change-in-a-patient-with-signs-of-potential-sepsis-and-parkinson-hyperpyrexia-syndrome-a-case-report
#12
Chyong-Jy Joyce Liu, Anica Crnkovic, John Dalfino, Leina Yoko Singh
Parkinsonism-hyperpyrexia syndrome (PHS) is a neurologic emergency associated with anti-Parkinson medication withdrawal; however, its clinical presentation mimics sepsis. We describe the case of a 69-year-old man with advanced Parkinson disease who presented for exchange of the depleted battery in his subthalamic deep brain stimulator. The patient's preoperative symptoms of fever, rigidity, altered consciousness, and autonomic instability presented a dilemma whether to proceed with battery exchange to treat PHS or postpone surgery due to potential sepsis...
February 3, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28149827/a-case-of-rapid-progression-of-postoperative-hyperthermia-dantrolene-or-not-dilemma
#13
Marzieh R Honardar, Jesus Rubio, Sanjay M Bhananker
Malignant hyperthermia (MH) is an extremely rare and life-threatening differential diagnosis of postoperative fever. We present an 8-month-old child scheduled for elective outpatient procedure who rapidly developed high fever, tachycardia, and respiratory acidosis shortly after transfer to the postanesthesia care unit. MH hotline expert recommended administering dantrolene, but there was no evidence of hypermetabolism or lactic acidosis. The patient remained clinically stable after admission to the pediatric intensive care unit and was discharged home the next day...
October 2016: International Journal of Critical Illness and Injury Science
https://www.readbyqxmd.com/read/28138998/current-and-prospective-sights-in-mechanism-of-deoxynivalenol-induced-emesis-for-future-scientific-study-and-clinical-treatment
#14
REVIEW
Liangkai Chen, Zhao Peng, Andreas K Nüssler, Liegang Liu, Wei Yang
Deoxynivalenol (DON), one of trichothecene mycotoxins produced by the fungus Fusarium, is commonly detected in cereal foods and in secondary food production across the world. Lower concentrations of DON induce a dose-related feed refusal (anorexia), whereas it acts as a potent emetic agent at higher levels. DON-induced emesis in humans and livestock can be observed and recorded in both undeveloped and developed regions such as Lixian, Guide and Huangzhong in China and Illinois in the USA. Some studies with different animal models (pigs and minks) suggested that DON could change expressions of 5-hydroxytryptamine, peptide YY, neuropeptide Y2 receptor and nucleobindin-2/nesfatin-1 in plasma and different areas of the brain...
January 31, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28132918/ciproxifan-a-histamine-h3-receptor-antagonist-and-inverse-agonist-presynaptically-inhibits-glutamate-release-in-rat-hippocampus
#15
Cheng-Wei Lu, Tzu-Yu Lin, Chia-Ying Chang, Shu-Kuei Huang, Su-Jane Wang
Ciproxifan is an H3 receptor antagonist and inverse agonist with antipsychotic effects in several preclinical models; its effect on glutamate release has been investigated in the rat hippocampus. In a synaptosomal preparation, ciproxifan reduced 4-aminopyridine (4-AP)-evoked Ca(2+)-dependent glutamate release and cytosolic Ca(2+) concentration elevation but did not affect the membrane potential. The inhibitory effect of ciproxifan on 4-AP-evoked glutamate release was prevented by the Gi/Go-protein inhibitor pertussis toxin and Cav2...
January 27, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28111173/cardiac-expression-of-ryanodine-receptor-subtype-3-a-strategic-component-in-the-intracellular-ca-2-release-system-of-purkinje-fibers-in-large-mammalian-heart
#16
Rebecca E Daniels, Kazi T Haq, Lawson S Miller, Elizabeth W Chia, Masahito Miura, Vincenzo Sorrentino, John J McGuire, Bruno D Stuyvers
BACKGROUND: Three distinct Ca(2+) release channels were identified in dog P-cells: the ryanodine receptor subtype 2 (RyR2) was detected throughout the cell, while the ryanodine receptor subtype 3 (RyR3) and inositol phosphate sensitive Ca(2+) release channel (InsP3R) were found in the cell periphery. How each of these channels contributes to the Ca(2+) cycling of P-cells is unclear. Recent modeling of Ca(2+) mobilization in P-cells suggested that Ca(2+) sensitivity of Ca(2+)induced Ca(2+)release (CICR) was larger at the P-cell periphery...
January 20, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28098197/dantrolene-versus-amiodarone-for-cardiopulmonary-resuscitation-a-randomized-double-blinded-experimental-study
#17
Thomas Wiesmann, Dennik Freitag, Wolfgang Dersch, Daphne Eschbach, Marc Irqsusi, Thorsten Steinfeldt, Hinnerk Wulf, Carsten Feldmann
Dantrolene was introduced for treatment of malignant hyperthermia. It also has antiarrhythmic properties and may thus be an alternative to amiodarone for the treatment of ventricular fibrillation (VF). Aim of this study was to compare the return of spontaneous circulation (ROSC) with dantrolene and amiodarone in a pig model of cardiac arrest. VF was induced in anesthetized pigs. After 8 min of untreated VF, chest compressions and ventilation were started and one of the drugs (amiodarone 5 mg kg(-1), dantrolene 2...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28079659/suspected-malignant-hyperthermia-in-the-setting-of-hypothermic-circulatory-arrest-for-type-a-aortic-dissection-repair-a-case-report
#18
Bryant Bunting, Joshua Knight, Stephen M McHugh
Malignant Hyperthermia (MH) is a life-threatening biochemical process of hypermetabolism brought about in susceptible individuals by a triggering drug or event. Type A aortic dissections are surgical emergencies requiring cardiopulmonary bypass and frequently deep hypothermic circulatory arrest. We present a case of suspected MH in a patient undergoing emergent repair of a type A aortic dissection. Upon arrival at our institution, the patient had multiple signs of MH. However, no known triggering agent had been administered...
March 1, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28079567/cardiac-calcium-release-channel-ryanodine-receptor-2-regulation-by-halogenated-anesthetics
#19
Derek R Laver, John Attia, Christopher Oldmeadow, Anthony W Quail
BACKGROUND: Halogenated anesthetics activate cardiac ryanodine receptor 2-mediated sarcoplasmic reticulum Ca release, leading to sarcoplasmic reticulum Ca depletion, reduced cardiac function, and providing cell protection against ischemia-reperfusion injury. Anesthetic activation of ryanodine receptor 2 is poorly defined, leaving aspects of the protective mechanism uncertain. METHODS: Ryanodine receptor 2 from the sheep heart was incorporated into artificial lipid bilayers, and their gating properties were measured in response to five halogenated anesthetics...
March 2017: Anesthesiology
https://www.readbyqxmd.com/read/28035645/reflex-arc-of-the-teeth-clenching-induced-pressor-response-in-rats
#20
Ichiro Shoji, Takehito Kemuriyama, Megumi Tandai-Hiruma, Satoshi Maruyama, Akimasa Tashiro, Hidetaka Yokoe, Yasuhiro Nishida
Although "teeth clenching" induces pressor response, the reflex tracts of the response are unknown. In this study, dantrolene administration inhibited teeth clenching generated by electrical stimulation of the masseter muscles and completely abolished the pressor response. In addition, trigeminal ganglion block or hexamethonium administration completely abolished the pressor response. Local anesthesia of molar regions significantly reduced the pressor response to 27 ± 10%. Gadolinium (mechanoreceptor blocker of group III muscle afferents) entrapment in masticatory muscles also significantly reduced the pressor response to 62 ± 7%...
December 29, 2016: Journal of Physiological Sciences: JPS
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