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Dantrolene

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https://www.readbyqxmd.com/read/28808649/the-effect-of-a-single-dose-dantrolene-in-patients-with-vasospasm-following-aneurysmal-subarachnoid-hemorrhage
#1
Masih Sabouri, Mahmood Momeni, Fariborz Khorvash, Majid Rezvani, Homayon Tabesh
BACKGROUND: Cerebral vasospasm is a prolonged, occasionally severe, but reversible narrowing of the cerebral arteries that begins 3 to 5 days after the hemorrhage becomes maximal at 14 days. This study is designed to evaluate the effect of dantrolene on the reduction of vasospasm following aneurysmal subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: This randomized controlled clinical trial was conducted on 32 patients with proven aneurysms in AL-Zahra hospital during 2011-2013...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/28752347/-prolonged-neuroleptic-malignant-syndrome-after-haloperidol-injection
#2
N Wystub, S Heymel, M Fritzenwanger, P C Schulze, R Pfeifer
Neuroleptic malignant syndrome (NMS) is a rare disorder caused by drug-induced dopamine-receptor-blockage or low dopamine concentration in the brain. It is a severe reaction to neuroleptic drugs in antipsychotic therapy. Symptoms in NMS typically consist of fever, muscle rigidity and cognitive changes; laboratory findings include elevated infectious disease markers and creatine kinase as well as signs of rhabdomyolysis. To differentiate NMS from other malignant hyperthermia syndromes identifying the offending drug and clinical history are essential...
July 27, 2017: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/28717166/targeting-cellular-calcium-homeostasis-to-prevent-cytokine-mediated-beta-cell-death
#3
Amy L Clark, Kohsuke Kanekura, Zeno Lavagnino, Larry D Spears, Damien Abreu, Jana Mahadevan, Takuya Yagi, Clay F Semenkovich, David W Piston, Fumihiko Urano
Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697029/malignant-hyperthermia-in-a-morbidly-obese-patient-depletes-community-dantrolene-resources-a-case-report
#4
Fabio Magistris, Jonathan Gamble
During resection of a duodenal carcinoid tumor, a 28-year-old morbidly obese woman developed suspected malignant hyperthermia. This hypermetabolic state posed a diagnostic challenge given the similar intraoperative presentation of carcinoid crisis and malignant hyperthermia. The patient's weight posed therapeutic challenges as massive doses and prolonged administration of dantrolene were required that quickly depleted the available supply. Current dantrolene dosing recommendations are based on actual body weight despite a paucity of literature in obese patients...
July 10, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28687594/reduced-threshold-for-store-overload-induced-ca-2-release-is-a-common-defect-of-ryr1-mutations-associated-with-malignant-hyperthermia-and-central-core-disease
#5
Wenqian Chen, Andrea Koop, Yingjie Liu, Wenting Guo, Jinhong Wei, Ruiwu Wang, David H MacLennan, Robert T Dirksen, S R Wayne Chen
Mutations in the skeletal muscle ryanodine receptor (RyR1) cause malignant hyperthermia (MH) and central core disease (CCD), while mutations in the cardiac ryanodine receptor (RyR2) lead to catecholaminergic polymorphic ventricular tachycardia (CPVT). Most disease-associated RyR1 and RyR2 mutations are located in the N-terminal, central, and C-terminal regions of the corresponding RyR isoform. An increasing body of evidence demonstrates that CPVT-associated RyR2 mutations enhance the propensity for spontaneous Ca(2+) release during store Ca(2+) overload, a process known as store-overload induced Ca(2+) release (SOICR)...
July 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28660414/-stocks-of-dantrolene-in-anesthesia-and-intensive-care-units-in-germany-nationwide-online-survey-with-1673-participants
#6
E Pfenninger, S Heiderich, W Klingler
BACKGROUND: A malignant hyperthermia (MH) crisis is a potentially fatal complication in anesthesia and intensive care units (ICU). Rapid administration and adequate dosage of dantrolene is the only known effective pharmacological and causal treatment of an MH crisis. International anesthesiology societies recommend an initial dose of 2.0-2.5 mg/kg body weight (BW). The necessary total dosage should be titrated up to 10 mg/kg BW depending on the effectiveness. OBJECTIVE: The goal of this study was an analysis of the stocking situation of dantrolene in Germany...
June 28, 2017: Der Anaesthesist
https://www.readbyqxmd.com/read/28630284/differential-interaction-of-dantrolene-glafenine-nalidixic-acid-and-prazosin-with-human-organic-anion-transporters-1-and-3-oat1-oat3
#7
Birgitta C Burckhardt, Maja Henjakovic, Yohannes Hagos, Gerhard Burckhardt
In renal proximal tubule cells, the organic anion transporters 1 and 3 (OAT1 and OAT3) in the basolateral membrane and the multi drug resistance-associated protein 4 (MRP4) in the apical membrane share substrates and co-operate in renal drug secretion. We hypothetized that recently identified MRP4 inhibitors, dantrolene, glafenine, nalidixic acid, and prazosin, also interact with human OAT1 and/or OAT3 stably transfected in HEK293 cells. These four drugs were tested as possible inhibitors of p-[3H]aminohippurate (PAH) and [14C]glutarate uptake by OAT1, and of [3H]estrone-3-sulfate (ES) uptake by OAT3...
June 19, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28619610/forecasting-gastrointestinal-precipitation-and-oral-pharmacokinetics-of-dantrolene-in-dogs-using-an-in-vitro-precipitation-testing-coupled-with-in-silico-modeling-and-simulation
#8
Atsushi Kambayashi, Jennifer B Dressman
The aim of the current research was to determine the precipitation kinetics of dantrolene sodium using canine biorelevant in vitro testing and to model the precipitation kinetics by appropriately coupling the data with an in silico tool adapted for dogs. The precipitation profiles of dantrolene sodium solutions were obtained with the in vitro paddle apparatus at a revolution rate of 50 rpm. The in silico prediction tool was designed using STELLA software and the predicted plasma concentration profiles of dantrolene using the in vitro precipitation data were compared with the observed in vivo pharmacokinetics in beagle dogs...
June 12, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28596111/high-fat-diet-disrupts-endoplasmic-reticulum-calcium-homeostasis-in-the-rat-liver
#9
Emily S Wires, Kathleen A Trychta, Susanne Bäck, Agnieszka Sulima, Kenner C Rice, Brandon K Harvey
BACKGROUND & AIMS: Disruption to endoplasmic reticulum (ER) calcium homeostasis has been implicated in obesity, however, the ability to longitudinally monitor ER calcium fluctuations has been challenging with prior methodologies. We recently described the development of a Gaussia luciferase (GLuc)- based reporter protein responsive to ER calcium depletion (GLuc-SERCaMP) and investigated the effect of a high fat diet on ER calcium homeostasis. METHODS: A GLuc-based reporter cell line was treated with palmitate, a free fatty acid (FFA)...
June 5, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28571205/postoperative-malignant-hyperthermia-a-medical-emergency-a-case-report-and-review-of-literature
#10
Amit Kumar Sinha, Poonam Kumari, Maheshkumar Manilal Vaghela, Chandni Sinha, Bindey Kumar
Malignant hyperthermia is a rare life threatening pharmacological disorder. Preoperative clinical diagnosis is not possible. Due to its rarity and severity, it must be taken as an important differential diagnosis for postoperative hyperthermia. We hereby report a case of postoperative malignant hyperthermia in a four-year-old female child, who was operated for type 1 choledochal cyst and had difficult postoperative sequel. We lost that child due to unavailability of Dantrolene sodium in emergency drug cart.
April 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28568606/coupling-of-excitation-to-ca-2-release-is-modulated-by-dysferlin
#11
Valeriy Lukyanenko, Joaquin M Muriel, Robert J Bloch
KEY POINTS: Dysferlin, the protein missing in limb girdle muscular dystrophy 2B and Miyoshi myopathy, concentrates in transverse tubules of skeletal muscle, where it stabilizes voltage-induced Ca(2+) transients against loss after osmotic shock injury (OSI). Local expression of dysferlin in dysferlin-null myofibres increases transient amplitude to control levels and protects them from loss after OSI. Inhibitors of ryanodine receptors (RyR1) and L-type Ca(2+) channels protect voltage-induced Ca(2+) transients from loss; thus both proteins play a role in injury in dysferlin's absence...
August 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28549333/endoplasmic-reticulum-er-stress-and-camp-pka-pathway-mediated-zn-induced-hepatic-lipolysis
#12
Yu-Feng Song, Christer Hogstrand, Chuan-Chuan Wei, Kun Wu, Ya-Xiong Pan, Zhi Luo
The present study was performed to determine the effect of Zn exposure influencing endoplasmic reticulum (ER) stress, explore the underlying molecular mechanism of Zn-induced hepatic lipolysis in a fish species of significance for aquaculture, yellow catfish Pelteobagrus fulvidraco. We found that waterborne Zn exposure evoked ER stress and unfolded protein response (UPR), and activated cAMP/PKA pathway, and up-regulated hepatic lipolysis. The increase in ER stress and lipolysis were associated with activation of cAMP/PKA signaling pathway...
September 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28498149/inhibition-of-glutamate-release-by-cilnidipine-in-rat-cerebrocortical-nerve-terminals-synaptosomes
#13
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
#14
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
#15
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
#16
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 was investigated using Mrp4(-/-) mice. Significant adenosine triphosphate-dependent uptake by MRP4 was observed for ochratoxin A, pitavastatin, raltitrexed (Km = 43.7 μM), pravastatin, cyclic guanosine monophosphate, 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 27, 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
#17
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
#18
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
#19
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
#20
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
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