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Po-Hao Chen, Hsien-Yuan Lane, Chieh-Hsin Lin
Neuroleptic malignant syndrome (NMS) is one of the most severe iatrogenic emergencies in clinical service. The symptoms including sudden consciousness change, critical temperature elevation and electrolytes imbalance followed by mutli-organ system failure were common in NMS. In addition to aggressive interventions with intravenous fluid resuscitation and antipyretics, several antidotes have been suggested to prevent further progression of the muscle damage. Dantrolene has been reported to be one of the most effective treatments for NMS...
November 30, 2016: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
Lygia M Malvestio, Mara Rúbia N Celes, Linda A Jelicks, Herbert B Tanowitz, Cibele M Prado
Dystrophin, an important protein of the dystrophin-glycoprotein complex, has been implicated in the pathogenesis of experimental Chagas disease. It is important for the maintenance of cell shape and contraction force transmission. Dystrophin loss has been related to end-stage cardiac myopathies and proposed as a common route for myocardial dysfunction and progression to advanced heart failure. Evidence suggests that calpains, calcium-dependent proteases, digest dystrophin when the calcium concentration is compatible with their activation...
October 11, 2016: Parasitology Research
Jaspinder Kaur, Dileep Kumar, Mostafa Alfishawy, Ricardo Lopez, Issac Sachmechi
Paliperidone, an active metabolite of risperidone, is a new atypical antipsychotic agent. Syndrome of inappropriate antidiuretic hormone (SIADH), neuroleptic malignant syndrome (NMS), and rhabdomyolysis are the uncommon side effects of psychotropic drugs. We report a case of 35-year-old male with schizoaffective disorder who was admitted for acute-on-chronic exacerbation of his psychotic disorder for which intramuscular paliperidone 234 mg injection was given. Two days later, the patient developed hyponatremic seizures secondary to SIADH which was treated with hypertonic saline...
2016: Case Reports in Critical Care
R M Downs, M A Hughes, S T Kinsey, M C Johnson, B L Baumgarner
Caffeine is a widely consumed stimulant that has previously been shown to promote cytotoxic stress and even cell death in numerous mammalian cell lines. Thus far there is little information available regarding the toxicity of caffeine in skeletal muscle cells. Our preliminary data revealed that treating C2C12 myotubes with 5 mM caffeine for 6 h increased nuclear fragmentation and reduced basal and maximal oxygen consumption rate (OCR) in skeletal myotubes. The purpose of this study was to further elucidate the pathways by which caffeine increased cell death and reduced mitochondrial respiration...
October 4, 2016: Biochemical and Biophysical Research Communications
Nico Hartmann, Steffen Pabel, Jonas Herting, Felix Schatter, André Renner, Jan Gummert, Hanna Schotola, Bernhard C Danner, Lars S Maier, Norbert Frey, Gerd Hasenfuss, Thomas H Fischer, Samuel Sossalla
BACKGROUND: Cardiac type 2 ryanodine receptors (RyR2s) play a pivotal role in cellular electrophysiology and contractility. Increased RyR2-mediated diastolic sarcoplasmic reticulum (SR) Ca(2+) release is linked to heart failure (HF) and arrhythmias. Dantrolene, a drug used for the treatment of malignant hyperthermia, is known to stabilize RyRs in skeletal muscle. OBJECTIVE: The purpose of this study was to investigate the effects of dantrolene on arrhythmogenic triggers and contractile function in human atrial fibrillation (AF) and HF cardiomyocytes (CM)...
September 17, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
A Kollmann-Camaiora, E Alsina, A Domínguez, B Del Blanco, M J Yepes, J L Guerrero, A García
Malignant hyperthermia is a hypermetabolic syndrome that appears in susceptible patients after exposure to certain anaesthetic drugs (succinylcholine, inhalation anaesthetics). Its incidence in Spain is 1 in 40,000 adults, with a 10% mortality rate. It is induced by an abnormal regulation of the ryanodine receptors, producing a massive release of calcium from the sarcoplasmic reticulum in the striate muscle. Clinical manifestations include: CO2 increase, tachycardia, haemodynamic instability, metabolic and respiratory acidosis, profuse sweating, hyperpyrexia, CPK increase, myoglobinuria, kidney failure, disseminated intravascular coagulation (DIC), and ending in cardiac arrest...
September 12, 2016: Revista Española de Anestesiología y Reanimación
Kafa Walweel, Ye Win Oo, Derek R Laver
Cardiac output and rhythm depend on the release and the take-up of calcium from the sarcoplasmic reticulum (SR). Excessive diastolic calcium leak from the SR due to dysfunctional calcium release channels (RyR2) contributes to the formation of delayed after-depolarisations, which underlie the fatal arrhythmias that occur in heart failure and inherited syndromes. Calmodulin (CaM) is a calcium-binding protein that regulates target proteins and acts as a calcium sensor. CaM is comprised of two calcium binding EF-hand domains and a flexible linker...
September 14, 2016: Clinical and Experimental Pharmacology & Physiology
Gunchan Paul, Gautam L Parshotam, Rajneesh Garg
Soma (Carisoprodol) is N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; a commonly prescribed, centrally acting skeletal muscle relaxant. Neuroleptic malignant syndrome (NMS) is a potentially life-threatening adverse effect of antipsychotic agents. Although diagnostic criteria for NMS have been established, it should be recognized that atypical presentations occur and more flexible diagnostic criteria than currently mandated, may be warranted. We wish to report a postoperative case of bilateral knee replacement who presented with carisoprodol (Soma) withdrawal resembling NMS that was a diagnostic dilemma...
July 2016: Journal of Anaesthesiology, Clinical Pharmacology
Theresa Cummings, Tara Der, Cengiz Karsli
A series of life-threatening nonanesthetic-related MH reactions in a child was the inspiration for a proactive, novel solution allowing for early prehospital, potentially lifesaving intravenous dantrolene administration. Multidisciplinary collaboration is essential and parent education must be comprehensive and ongoing. This case underlines the importance of considering nonanesthetic MH susceptibility in the child who has a history of unspecified myopathy and who presents with fever and total body stiffness...
August 26, 2016: Paediatric Anaesthesia
Yoshinori Mikami, Kazunori Kanemaru, Yohei Okubo, Takuya Nakaune, Junji Suzuki, Kazuki Shibata, Hiroki Sugiyama, Ryuta Koyama, Takashi Murayama, Akihiro Ito, Toshiko Yamazawa, Yuji Ikegaya, Takashi Sakurai, Nobuhito Saito, Sho Kakizawa, Masamitsu Iino
Status epilepticus (SE) is a life-threatening emergency that can cause neurodegeneration with debilitating neurological disorders. However, the mechanism by which convulsive SE results in neurodegeneration is not fully understood. It has been shown that epileptic seizures produce markedly increased levels of nitric oxide (NO) in the brain, and that NO induces Ca(2+) release from the endoplasmic reticulum via the type 1 ryanodine receptor (RyR1), which occurs through S-nitrosylation of the intracellular Ca(2+) release channel...
September 2016: EBioMedicine
Lea K Seidlmayer, Johannes Kuhn, Annette Berbner, Paula-Anahi Arias-Loza, Tatjana Williams, Mathias Kaspar, Martin Czolbe, Jennifer Q Kwong, Jeffery D Molkentin, Katrin Gertrud Heinze, Elena N Dedkova, Oliver Ritter
AIMS: Elevated levels of inositol 1,4,5-trisphosphate (IP3) in adult cardiac myocytes are typically associated with the development of cardiac hypertrophy, arrhythmias, and heart failure. IP3 enhances intracellular Ca(2+ )release via IP3 receptors (IP3Rs) located at the sarcoplasmic reticulum (SR). We aimed to determine whether IP3-induced Ca(2+ )release affects mitochondrial function and determine the underlying mechanisms. METHODS AND RESULTS: We compared the effects of IP3Rs- and ryanodine receptors (RyRs)-mediated cytosolic Ca(2+ )elevation achieved by endothelin-1 (ET-1) and isoproterenol (ISO) stimulation, respectively, on mitochondrial Ca(2+ )uptake and adenosine triphosphate (ATP) generation...
October 2016: Cardiovascular Research
Dominic J Pileggi, Aaron M Cook
OBJECTIVE: To review evidence for the treatment of neuroleptic malignant syndrome (NMS) and to discuss how to rechallenge patients with neuroleptics when continued pharmacotherapy for chronic psychological illness is required. DATA SOURCES: A PubMed search was conducted through March 2016 using available medical subject heading (MeSH) terms and keywords that included neuroleptic malignant syndrome, treatment, dantrolene, and bromocriptine A manual search of article reference sections followed...
July 15, 2016: Annals of Pharmacotherapy
Rubén J Lopez, Susan Byrne, Mirko Vukcevic, Marijana Sekulic-Jablanovic, Lifen Xu, Marijke Brink, Jay Alamelu, Nicol Voermans, Marc Snoeck, Emma Clement, Francesco Muntoni, Haiyan Zhou, Aleksandar Radunovic, Shehla Mohammed, Elizabeth Wraige, Francesco Zorzato, Susan Treves, Heinz Jungbluth
Malignant hyperthermia is a potentially fatal hypermetabolic disorder triggered by halogenated anesthetics and the myorelaxant succinylcholine in genetically predisposed individuals. About 50% of susceptible individuals carry dominant, gain-of-function mutations in RYR1 [which encodes ryanodine receptor type 1 (RyR1)], though they have normal muscle function and no overt clinical symptoms. RyR1 is predominantly found in skeletal muscle but also at lower amounts in immune and smooth muscle cells, suggesting that RYR1 mutations may have a wider range of effects than previously suspected...
2016: Science Signaling
Sevtap Hekimoğlu Şahin, Mustafa İnan, Burhan Aksu, Naci Öner, Alkin Çolak, Ahmet Güzel
Malignant hyperthermia (MH) is a rare and potentially life threatening fatal complication of anaesthesia. We present a 2-year-old boy with late onset MH after colon interposition to replace the oesophagus under sevoflurane anaesthesia. The patient was treated with intravenous dantrolene sodium as well as cooling and controlled ventilation. Despite treatment, the patient developed cardiopulmonary arrest at 21 hours after the operation and died. It should be kept in mind that post-operative MH may develop during these types of operations with ischaemia-reperfusion injuries...
December 2015: Turkish Journal of Anaesthesiology and Reanimation
Cheng Wei Lu, Tzu Yu Lin, Shu Kuei Huang, Su Jane Wang
The glutamatergic system may be involved in the effects of neuroprotectant therapies. Echinacoside, a phenylethanoid glycoside extracted from the medicinal Chinese herb Herba Cistanche, has neuroprotective effects. This study investigated the effects of echinacoside on 4-aminopyridine-evoked glutamate release in rat cerebrocortical nerve terminals (synaptosomes). Echinacoside inhibited Ca(2+)-dependent, but not Ca(2+)-independent, 4-aminopyridine-evoked glutamate release in a concentration-dependent manner...
2016: International Journal of Molecular Sciences
Stephen J Gleich, Kim Strupp, Robert T Wilder, Daryl J Kor, Randall Flick
BACKGROUND: Malignant hyperthermia (MH) is a rare anesthetic pharmacogenetic disorder that can be difficult to detect in its earliest phases. Prompt treatment is known to improve outcomes. The modern anesthesia information management systems (AIMS) collect enormous amounts of data. However, data lack context and are not able to provide real-time guidance. Utilizing our AIMS, we developed the capacity to incorporate decision support. AIMS: We describe the creation and evaluation of a real-time detection tool for MH...
September 2016: Paediatric Anaesthesia
Laxmikant S Deshpande, Robert E Blair, Kristin F Phillips, Robert J DeLorenzo
Organophosphate (OP) chemicals include nerve agents and pesticides, and there is a growing concern of OP-based chemical attacks against civilians. Current antidotes are essential in limiting immediate mortality associated with OP exposure. However, further research is needed to identify the molecular mechanisms underlying long-term neurological deficits following survival of OP toxicity in order to develop effective therapeutics. We have developed rat survival models of OP-induced status epilepticus (SE) that mimic chronic mortality and morbidity following OP intoxication...
June 2016: Annals of the New York Academy of Sciences
Hitoshi Uchinoumi, Yi Yang, Tetsuro Oda, Na Li, Katherina M Alsina, Jose L Puglisi, Ye Chen-Izu, Razvan L Cornea, Xander H T Wehrens, Donald M Bers
Diastolic calcium (Ca) leak via cardiac ryanodine receptors (RyR2) can cause arrhythmias and heart failure (HF). Ca/calmodulin (CaM)-dependent kinase II (CaMKII) is upregulated and more active in HF, promoting RyR2-mediated Ca leak by RyR2-Ser2814 phosphorylation. Here, we tested a mechanistic hypothesis that RyR2 phosphorylation by CaMKII increases Ca leak by promoting a pathological RyR2 conformation with reduced CaM affinity. Acute CaMKII activation in wild-type RyR2, and phosphomimetic RyR2-S2814D (vs. non-phosphorylatable RyR2-S2814A) knock-in mouse myocytes increased SR Ca leak, reduced CaM-RyR2 affinity, and caused a pathological shift in RyR2 conformation (detected via increased access of the RyR2 structural peptide DPc10)...
September 2016: Journal of Molecular and Cellular Cardiology
Keisuke Kameda, Kazuhiro Watarai, Kenji Takahashi, Tomohisa Shoko, Masayoshi Koinuma, Goro Ikushima
Since 2012, Matsudo City Hospital has increased the number of pharmacists stationed in the ward on weekday mornings at the emergency care center, the intensive care unit (ICU) and the high care unit (HCU). Multidisciplinary joint meetings and joint conferences are conducted in the emergency care center, and patient and drug information is shared. A 20-year-old man was transferred to our hospital after a traffic accident. He was diagnosed with subarachnoid hemorrhage and brain contusion. He exhibited violent movement and intense restlessness...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Laxmikant S Deshpande, Robert E Blair, Beverly A Huang, Kristin F Phillips, Robert J DeLorenzo
Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10mg/kg, i...
July 2016: Neurotoxicology and Teratology
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