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https://www.readbyqxmd.com/read/28498149/inhibition-of-glutamate-release-by-cilnidipine-in-rat-cerebrocortical-nerve-terminals-synaptosomes
#1
Cheng Wei Lu, Tzu Yu Lin, Shu Kuei Huang, Su Jane Wang
Cilnidipine is an antihypertensive drug that was reported to have a neuroprotective profile. The present study aimed to investigate the effect of cilnidipine on the 4-aminopyridine (4-AP)-induced glutamate release in the rat cerebral cortex using isolated nerve terminals (synaptosomes). Cilnidipine reduced the release of glutamate release induced by 4-AP in a concentration-dependent manner. This inhibitory effect was associated with a reduction in the 4-AP-induced intrasynaptosomal Ca concentration elevation and was not because of an alteration of the synaptosomal membrane potential...
June 14, 2017: Neuroreport
https://www.readbyqxmd.com/read/28490900/complex-management-of-a-patient-with-refractory-primary-erythromelalgia-lacking-a-scn9a-mutation
#2
Sarah A Low, Wendye Robbins, Vivianne L Tawfik
A 41-year-old woman presented with burning and erythema in her extremities triggered by warmth and activity, which was relieved by applying ice. Extensive workup was consistent with adult-onset primary erythromelalgia (EM). Several pharmacological treatments were tried including local anesthetics, capsaicin, ziconotide, and dantrolene, all providing 24-48 hours of relief followed by symptom flare. Interventional therapies, including peripheral and sympathetic ganglion blocks, also failed. Thus far, clonidine and ketamine have been the only effective agents for our patient...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28469577/interference-with-ca-2-dependent-proteolysis-does-not-alter-the-course-of-muscle-wasting-in-experimental-cancer-cachexia
#3
Fabrizio Pin, Valerio G Minero, Fabio Penna, Maurizio Muscaritoli, Roberta De Tullio, Francesco M Baccino, Paola Costelli
Protein hypercatabolism significantly contributes to the onset and progression of muscle wasting in cancer cachexia. In this regard, a major role is played by the ATP-ubiquitin-proteasome-dependent pathway and by autophagy. However, little is known about the relevance of the Ca(2+)-dependent proteolytic system. Since previous results suggested that this pathway is activated in the skeletal muscle of tumor hosts, the present study was aimed to investigate whether inhibition of Ca(2+)-dependent proteases (calpains) may improve cancer-induced muscle wasting...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28456721/investigation-of-the-importance-of-multidrug-resistance-associated-protein-4-mrp4-abcc4-in-the-active-efflux-of-anionic-drugs-across-the-blood-brain-barrier
#4
Kayoko Kanamitsu, Hiroyuki Kusuhara, John D Schuetz, Kenji Takeuchi, Yuichi Sugiyama
The importance of multidrug resistance-associated protein 4 (Mrp4/Abcc4) in limiting the penetration of Mrp4 substrate compounds into the central nervous system across the blood-brain barrier (BBB) was investigated using Mrp4(-/-) mice. Significant ATP-dependent uptake by MRP4 was observed for ochratoxin A, pitavastatin, raltitrexed (Km 43.7 μM), pravastatin, cGMP, 2,4-dichlorophenoxyacetate, and urate. The defect in the Mrp4 gene did not affect the brain-to-plasma ratio (Kp,brain) of quinidine and dantrolene...
April 26, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28444183/calcium-dysregulation-and-cdk5-atm-pathway-involved-in-a-mouse-model-of-fragile-x-associated-tremor-ataxia-syndrome
#5
Gaëlle Robin, José R López, Glenda M Espinal, Susan Hulsizer, Paul J Hagerman, Isaac N Pessah
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurological disorder that affects premutation carriers with 55-200 CGG-expansion repeats (preCGG) in FMR1, presenting with early alterations in neuronal network formation and function that precede neurodegeneration. Whether intranuclear inclusions containing DNA damage response (DDR) proteins, are causally linked to abnormal synaptic function, neuronal growth and survival are unknown. In a mouse that harbors a premutation CGG expansion (preCGG), cortical and hippocampal FMRP expression is moderately reduced from birth through adulthood, with greater FMRP reductions in the soma than in the neurite, despite several-fold elevation of Fmr1 mRNA levels...
April 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28442967/a-case-report-of-suspected-malignant-hyperthermia-where-patient-survived-the-episode
#6
Asif Iqbal, Shoaib Badoo, Ruqsana Naqeeb
Malignant hyperthermia is rare inherited disorder in our part of the world; there are only few cases reported in literature in India who were suspected of having this condition. The overall incidence of malignant hyperthermia during general anesthesia is estimated to range from 1: 5000 to 1: 50,000-100,000 and mortality rate is estimated to be <5% in the presence of standard care. In India, there is no center where in vitro halothane caffeine contraction test is performed to confirm diagnosis in suspected cases...
April 2017: Saudi Journal of Anaesthesia
https://www.readbyqxmd.com/read/28442565/mind-the-magnesium-in-dantrolene-suppression-of-malignant-hyperthermia
#7
Stephen C Cannon
No abstract text is available yet for this article.
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28435065/influence-of-er-leak-on-resting-cytoplasmic-ca-2-and-receptor-mediated-ca-2-signalling-in-human-macrophage
#8
Janice A Layhadi, Samuel J Fountain
Mechanisms controlling endoplasmic reticulum (ER) Ca(2+) homeostasis are important regulators of resting cytoplasmic Ca(2+) concentration ([Ca(2+)]cyto) and receptor-mediated Ca(2+) signalling. Here we investigate channels responsible for ER Ca(2+) leak in THP-1 macrophage and human primary macrophage. In the absence of extracellular Ca(2+) we employ ionomycin action at the plasma membrane to stimulate ER Ca(2+) leak. Under these conditions ionomycin elevates [Ca(2+)]cyto revealing a Ca(2+) leak response which is abolished by thapsigargin...
April 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28422845/response-to-benzodiazepines-and-the-clinical-course-in-malignant-catatonia-associated-with-schizophrenia-a-case-report
#9
Kazutaka Ohi, Aki Kuwata, Takamitsu Shimada, Toshiki Yasuyama, Yusuke Nitta, Takashi Uehara, Yasuhiro Kawasaki
BACKGROUND: Malignant catatonia (MC) is a disorder consisting of catatonic symptoms, hyperthermia, autonomic instability, and altered mental status. Neuroleptic malignant syndrome (NMS) caused by antipsychotics is considered a variant of MC. Benzodiazepine (BZD) medications are safe and effective treatments providing rapid relief from MC. This case study reports a detailed clinical course of a case of MC associated with schizophrenia initially diagnosed as NMS that responded successfully to BZDs but not to dantrolene...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28418433/capsaicin-presynaptically-inhibits-glutamate-release-through-the-activation-of-trpv1-and-calcineurin-in-the-hippocampus-of-rats
#10
Cheng Wei Lu, Tzu Yu Lin, Ting Yang Hsie, Shu Kuei Huang, Su Jane Wang
Capsaicin is the major ingredient in hot peppers of the plant Capsicum genus with neuroprotective effects in several preclinical models; its effect on glutamate release has been investigated in the rat hippocampus using isolated nerve terminals (synaptosomes) and brain slices. In a synaptosomal preparation, capsaicin dose-dependently reduced 4-aminopyridine-evoked Ca(2+)-dependent glutamate release, with an IC50 of approximately 11 μM. This inhibition was blocked by capsazepin, an antagonist of TRPV1, which was found to be colocalized with the vesicle marker protein synaptophysin in synaptosomes using double immunostaining...
April 18, 2017: Food & Function
https://www.readbyqxmd.com/read/28373535/dantrolene-requires-mg-2-to-arrest-malignant-hyperthermia
#11
Rocky H Choi, Xaver Koenig, Bradley S Launikonis
Malignant hyperthermia (MH) is a clinical syndrome of skeletal muscle that presents as a hypermetabolic response to volatile anesthetic gases, where susceptible persons may develop lethally high body temperatures. Genetic predisposition mainly arises from mutations on the skeletal muscle ryanodine receptor (RyR). Dantrolene is administered to alleviate MH symptoms, but its mechanism of action and its influence on the Ca(2+) transients elicited by MH triggers are unknown. Here, we show that Ca(2+) release in the absence of Mg(2+) is unaffected by the presence of dantrolene but that dantrolene becomes increasingly effective as cytoplasmic-free [Mg(2+)] (free [Mg(2+)]cyto) passes mM levels...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28330759/amiodarone-reduces-depolarization-evoked-glutamate-release-from-hippocampual-synaptosomes
#12
Chia Yu Chang, Chi Feng Hung, Shu Kuei Huang, Jinn Rung Kuo, Su Jane Wang
Decreased brain glutamate level has emerged as a new therapeutic approach for epilepsy. This study investigated the effect and mechanism of amiodarone, an anti-arrhythmic drug with antiepileptic activity, on glutamate release in the rat hippocampus. In a synaptosomal preparation, amiodarone reduced 4-aminopyridine-evoked Ca(2+)-dependent glutamate release and cytosolic Ca(2+) concentration elevation. Amiodarone did not affect the 4-aminopyridine-evoked depolarization of the synaptosomal membrane potential or the Na(+) channel activator veratridine-evoked glutamate release, indicating that the amiodarone-mediated inhibition of glutamate release is not caused by a decrease in synaptosomal excitability...
March 8, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28322744/basal-ryanodine-receptor-activity-suppresses-autophagic-flux
#13
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...
May 15, 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
May 2017: Anesthesiology
https://www.readbyqxmd.com/read/28246924/jsa-guideline-for-the-management-of-malignant-hyperthermia-crisis-2016
#20
(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...
April 2017: Journal of Anesthesia
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