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https://www.readbyqxmd.com/read/29772645/anticancer-activity-of-euplotin-c-isolated-from-the-marine-ciliate-euplotes-crassus-against-human-melanoma-cells
#1
Sara Carpi, Beatrice Polini, Giulio Poli, Gabriela Alcantara Barata, Stefano Fogli, Antonella Romanini, Tiziano Tuccinardi, Graziano Guella, Francesco Paolo Frontini, Paola Nieri, Graziano Di Giuseppe
Cutaneous melanoma is the most serious type of skin cancer, so new cytotoxic weapons against novel targets in melanoma are of great interest. Euplotin C (EC), a cytotoxic secondary metabolite of the marine ciliate Euplotes crassus , was evaluated in the present study on human cutaneous melanoma cells to explore its anti-melanoma activity and to gain more insight into its mechanism of action. EC exerted a marked cytotoxic effect against three different human melanoma cell lines (A375, 501Mel and MeWo) with a potency about 30-fold higher than that observed in non-cancer cells (HDFa cells)...
May 16, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29719463/compound-k-induced-apoptosis-via-endoplasmic-reticulum-ca-2-release-through-ryanodine-receptor-in-human-lung-cancer-cells
#2
Dong-Hyun Shin, Dong-Gyu Leem, Ji-Sun Shin, Joo-Il Kim, Kyung-Tack Kim, Sang Yoon Choi, Myung-Hee Lee, Jung-Hye Choi, Kyung-Tae Lee
Background: Extended endoplasmic reticulum (ER) stress may initiate apoptotic pathways in cancer cells, and ER stress has been reported to possibly increase tumor death in cancer therapy. We previously reported that caspase-8 played an important role in compound K-induced apoptosis via activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation in HL-60 human leukemia cells. The mechanisms leading to apoptosis in A549 and SK-MES-1 human lung cancer cells and the role of ER stress have not yet been understood...
April 2018: Journal of Ginseng Research
https://www.readbyqxmd.com/read/29674523/efficient-high-throughput-screening-by-er-ca-2-measurement-to-identify-inhibitors-of-ryanodine-receptor-ca2-release-channels
#3
Takashi Murayama, Nagomi Kurebayashi, Mari Ikegami-Yuasa, Shuichi Mori, Yukina Suzuki, Ryunosuke Akima, Haruo Ogawa, Junji Suzuki, Kazunori Kanemaru, Hideto Oyamada, Yuji Kiuchi, Masamitsu Iino, Hiroyuki Kagechika, Takashi Sakurai
Genetic mutations in ryanodine receptors (RyRs), Ca2+-release channels in the sarcoplasmic reticulum essential for muscle contractions, cause various skeletal muscle and cardiac diseases. Because the main underlying mechanism of the pathogenesis is overactive Ca2+ release by gain-of-function of the RyR channel, inhibition of RyRs is expected to be a promising treatment for these diseases. Here, to identify inhibitors specific to skeletal muscle type 1 RyR (RyR1), we developed a novel high-throughput screening (HTS) platform using time-lapse fluorescence measurement of Ca2+ concentrations in the endoplasmic reticulum (ER) ([Ca2+]ER)...
April 19, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29672336/cost-benefit-analysis-of-maintaining-a-fully-stocked-malignant-hyperthermia-cart-versus-an-initial-dantrolene-treatment-dose-for-maternity-units
#4
Phi T Ho, Brendan Carvalho, Eric C Sun, Alex Macario, Edward T Riley
BACKGROUND: The Malignant Hyperthermia Association of the United States recommends that dantrolene be available for administration within 10 min. One approach to dantrolene availability is a malignant hyperthermia cart, stocked with dantrolene, other drugs, and supplies. However, this may not be of cost benefit for maternity units, where triggering agents are rarely used. METHODS: The authors performed a cost-benefit analysis of maintaining a malignant hyperthermia cart versus a malignant hyperthermia cart readily available within the hospital versus an initial dantrolene dose of 250 mg, on every maternity unit in the United States...
April 19, 2018: Anesthesiology
https://www.readbyqxmd.com/read/29660904/ryanodine-receptor-antagonism-alleviates-skeletal-muscle-ischemia-reperfusion-injury-by-modulating-tnf-%C3%AE-and-il-10
#5
Hai-Peng Lin, Yan-Qing Zheng, Zhi-Ping Zhou, Gao-Xiong Wang, Ping-Fan Guo
BACKGROUND: Intracellular calcium overload has been implicated in various pathological conditions including ischemia reperfusion injury. This study aims to explore the effect and probable mechanism of dantrolene, a ryanodine receptor and intracellular calcium antagonist, on the skeletal muscle ischemia reperfusion injury. MATERIALS AND METHODS: SD rats were randomly divided into three groups: sham group which underwent anaesthesia and exposure of femoral vein, reperfusion group that received 2 h ischemia and the amount of diluent via femoral vein before 4 h reperfusion, dantrolene group that underwent 2 h ischemia and was given 2 mg/kg dantrolene via femoral vein before 4 h reperfusion...
April 13, 2018: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29608462/management-of-a-patient-with-a-history-of-nonanesthesia-related-malignant-hyperthermia-undergoing-laparoscopic-cholecystectomy-a-case-report
#6
Emily P Nelson, Margaret E Dorlon, Tamas A Szabo, Jonathan B Trollinger, Crystal Johnson-Mann, Gearin Broderick, Robert D Warters
A 36-year-old African American with a medical history of nonanesthesia-related malignant hyperthermia (MH) who was taking chronic oral dantrolene therapy presented with right upper quadrant pain for a laparoscopic cholecystectomy. A multidisciplinary perioperative plan was implemented with the goal of avoiding triggering an MH episode or rhabdomyolysis. He developed a postoperative left brachial vein thrombus of unclear etiology, possibly related to dantrolene administration or his underlying susceptibility to MH...
March 30, 2018: A&A practice
https://www.readbyqxmd.com/read/29600483/updated-guide-for-the-management-of-malignant-hyperthermia
#7
Sheila Riazi, Natalia Kraeva, Philip M Hopkins
PURPOSE: This continuing professional development module aims to prepare anesthesiologists for the timely recognition and management of a malignant hyperthermia (MH) reaction, which is crucial for averting its life-threatening complications and ultimately for the patient's survival. PRINCIPAL FINDINGS: Malignant hyperthermia is a genetic disorder of skeletal muscle cells affecting myoplasmic calcium homeostasis. It can present with nonspecific signs of a hypermetabolic reaction, which can be fatal if treatment, including administration of dantrolene sodium, is not implemented promptly...
March 29, 2018: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/29548378/dantrolene-for-treatment-of-suspected-neuroleptic-malignant-syndrome
#8
Colleen J Whyte, Jamie M Rosini
No abstract text is available yet for this article.
March 2018: Journal of Emergency Nursing: JEN: Official Publication of the Emergency Department Nurses Association
https://www.readbyqxmd.com/read/29547840/high-throughput-screen-of-drug-repurposing-library-identifies-inhibitors-of-sarcocystis-neurona-growth
#9
Gregory D Bowden, Kirkwood M Land, Roberta M O'Connor, Heather M Fritz
The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S...
February 16, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29540372/atrial-infarction-induced-spontaneous-focal-discharges-and-atrial-fibrillation-in-sheep-role-of-dantrolene-sensitive-aberrant-ryanodine-receptor-calcium-release
#10
Uma Mahesh R Avula, Jonathan J Hernandez, Masatoshi Yamazaki, Carmen R Valdivia, Antony Chu, Alvaro Rojas-Pena, Kuljeet Kaur, Roberto Ramos-Mondragón, Justus M Anumonwo, Stanley Nattel, Héctor H Valdivia, Jérôme Kalifa
BACKGROUND: The mechanisms underlying spontaneous atrial fibrillation (AF) associated with atrial ischemia/infarction are incompletely elucidated. Here, we investigate the mechanisms underlying spontaneous AF in an ovine model of left atrial myocardial infarction (LAMI). METHODS AND RESULTS: LAMI was created by ligating the atrial branch of the left anterior descending coronary artery. ECG loop recorders were implanted to monitor AF episodes. In 7 sheep, dantrolene-a ryanodine receptor blocker-was administered in vivo during the 8-day observation period (LAMI-D, 2...
March 2018: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/29522712/identification-of-enzymes-responsible-for-dantrolene-metabolism-in-the-human-liver-a-clue-to-uncover-the-cause-of-liver-injury
#11
Takayuki Amano, Tatsuki Fukami, Takuo Ogiso, Daisuke Hirose, Jeffrey P Jones, Tsuyoshi Taniguchi, Miki Nakajima
Dantrolene is used for malignant hyperthermia during anesthesia, and it sometimes causes severe liver injury as a side effect. Dantrolene is metabolized to acetylaminodantrolene, which is formed via the reduction of dantrolene to aminodantrolene and subsequent acetylation. Formation of hydroxylamine during the metabolic process may be associated with liver injury. We identified the enzymes responsible for dantrolene metabolism in humans to elucidate the mechanism of liver injury. Dantrolene reductase activity was not detected in human liver microsomes, but it was detected in cytosol...
May 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29521222/evaluation-of-drug-transport-in-mdckii-wild-type-mdckii-mdr1-mdckii-bcrp-and-caco-2-cell-lines
#12
Rao Mukkavilli, Gajanan Jadhav, Subrahmanyam Vangala
BACKGROUND: Drug transporters function as gatekeepers and modulate drug access into body and various tissues. Thus, a thorough and precise understanding of transporter liability for compound uptake and efflux is critical during drug development. METHODS: In the present study, we assessed the apparent permeability (Papp) and compared efflux ratio of various compounds in stably transfected Madin-Darby Canine Kidney (MDCKII) cells overexpressing human P-gp (MDCKII-MDR1), human BCRP (MDCKII-BCRP), wild-type (MDCKII-WT), and Caco-2 cell monolayers...
2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29480319/-abortive-course-of-malignant-hyperthermia-following-preclinical-induction-of-general-anesthesia-using-succinylcholine
#13
D Helf, D Schneiderbanger, C K Markus, S Johannsen, F Schuster
In a 59-year-old woman with a perforating eyeball injury to the right eye, the emergency physician induced a preclinical general anesthesia with propofol, fentanyl and the depolarizing muscle relaxant succinylcholine. Anesthesia was maintained using propofol and remifentanil infusion throughout the preoperative period and the subsequent surgical procedure. Postoperatively, isolated rhabdomyolysis with an increase in serum creatine kinase to >20,000 U/l was observed. The diagnosis of malignant hyperthermia (MH) susceptibility could be confirmed in the patient 4 months after the acute event by the in vitro contracture test and detection of the MH causative mutation p...
April 2018: Der Anaesthesist
https://www.readbyqxmd.com/read/29464848/corm-401-induces-calcium-signalling-no-increase-and-activation-of-pentose-phosphate-pathway-in-endothelial-cells
#14
Patrycja Kaczara, Bartosz Proniewski, Christopher Lovejoy, Kamil Kus, Roberto Motterlini, Andrey Y Abramov, Stefan Chlopicki
Carbon monoxide-releasing molecules (CO-RMs) induce nitric oxide (NO) release (which requires NADPH), and Ca2+ -dependent signalling; however, their contribution in mediating endothelial responses to CO-RMs is not clear. Here, we studied the effects of CO liberated from CORM-401 on NO production, calcium signalling and pentose phosphate pathway (PPP) activity in human endothelial cell line (EA.hy926). CORM-401 induced NO production and two types of calcium signalling: a peak-like calcium signal and a gradual increase in cytosolic calcium...
April 2018: FEBS Journal
https://www.readbyqxmd.com/read/29431655/fentanyl-induces-rapid-onset-hyperalgesic-priming-type-i-at-peripheral-and-type-ii-at-central-nociceptor-terminals
#15
Dioneia Araldi, Eugen V Khomula, Luiz F Ferrari, Jon D Levine
Systemic fentanyl induces hyperalgesic priming, long-lasting neuroplasticity in nociceptor function characterized by prolongation of inflammatory mediator hyperalgesia. To evaluate priming at both nociceptor terminals, we studied, in male Sprague Dawley rats, the effect of local administration of agents that reverse type I (protein translation) or type II [combination of Src and mitogen-activated protein kinase (MAPK)] priming. At the central terminal, priming induced by systemic, intradermal, or intrathecal fentanyl was reversed by the combination of Src and MAPK inhibitors, but at the peripheral terminal, it was reversed by the protein translation inhibitor...
February 28, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29416471/a-successful-anesthetic-approach-in-a-patient-with-schwartz-jampel-syndrome
#16
Fernando Calado de Oliveira Camacho, Tânia Marina Lopes Amaral, Joana Irene de Barros Mourão
Schwartz-Jampel syndrome (SJS) is a rare genetic condition that is characterized by several musculoskeletal abnormalities, such as myotonia, joint contractures, and facial dysmorphisms. Patients with this syndrome can present an anesthetic challenge, due to an increased risk of developing malignant hyperthermia (MH) and the possibility of encountering a difficult airway. Several precautions must be taken when general anesthesia is required, such as the avoidance of potential triggers for MH, continuous core temperature, and end-tidal CO2 monitoring, assuring that dantrolene is readily available...
January 2018: Saudi Journal of Anaesthesia
https://www.readbyqxmd.com/read/29402414/camkii-mediated-phosphorylation-of-ryr2-plays-a-crucial-role-in-aberrant-ca-2-release-as-an-arrhythmogenic-substrate-in-cardiac-troponin-t-related-familial-hypertrophic-cardiomyopathy
#17
Shinichi Okuda, Yoko Sufu-Shimizu, Takayoshi Kato, Masakazu Fukuda, Shigehiko Nishimura, Tetsuro Oda, Shigeki Kobayashi, Takeshi Yamamoto, Sachio Morimoto, Masafumi Yano
AIMS: Cardiac Troponin T (TnT) mutation-linked familial hypertrophic cardiomyopathy (FHC) is known to cause sudden cardiac death at a young age. Here, we investigated the role of the Ca2+ release channel of the cardiac sarcoplasmic reticulum (SR), ryanodine receptor (RyR2), in the pathogenic mechanism of lethal arrhythmia in FHC-related TnT-mutated transgenic mice (TG; TnT-delta160E). METHODS AND RESULTS: In TG cardiomyocytes, the Ca2+ spark frequency (SpF) was much higher than that in non-TG cardiomyocytes...
February 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29399547/caffeine-neuroprotective-mechanism-against-%C3%AE-amyloid-neurotoxicity-in-shsy5y-cell-line-involvement-of-adenosine-ryanodine-and-n-methyl-d-aspartate-receptors
#18
Mojtaba Keshavarz, Majid Reza Farrokhi, Atena Amiri
Purpose: Some reports have shown neuroprotective effects of caffeine in several neurodegenerative disorders. However, its mechanism of action is not completely clear. Therefore, the aim of this study was to explore the interference of ryanodine, N-methyl-D-aspartate (NMDA) and adenosine modulators with the neuroprotective effects of caffeine against β-amyloid (Aβ) neurotoxicity in the SHSY5Y cells. Methods: The SHSY5Y cells were treated with Aβ23-35 (20µM) and/or caffeine (0.6 and 1mM), or both for 24 hours...
December 2017: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29355282/malignant-hyperthermia-and-ryanodine-receptor-type-1-gene-ryr1-mutation-in-a-family-in-singapore
#19
Daphne Wy Li, Poh San Lai, Delice W Lee, Rita Yy Yong, Tat Leang Lee
INTRODUCTION: Sporadic clinical episodes of malignant hyperthermia (MH) that develop during general anaesthesia (GA) have been reported in Singapore. However, there is no published local report of a confirmed case of MH susceptibility (MHS) by skeletal muscle contracture tests and/or molecular tests. MATERIALS AND METHODS: We report 2 patients from an extended family who developed signs of clinical MH while under GA. The MH episodes were successfully treated with intravenous dantrolene sodium...
December 2017: Annals of the Academy of Medicine, Singapore
https://www.readbyqxmd.com/read/29335475/discontinuous-ventilator-weaning-of-patients-with-acute-sci
#20
Wout Füssenich, Sven Hirschfeld Araujo, Birgitt Kowald, Allard Hosman, Marc Auerswald, Roland Thietje
STUDY DESIGN: Retrospective, single centre cohort study. OBJECTIVES: To determine factors associated with ventilator weaning success and failure in patients with acute spinal cord injury (SCI); determine length of time and attempts required to wean from the ventilator successfully and determine the incidence of pneumonia. SETTING: BG Klinikum Hamburg, Level 1 trauma centre, SCI Department, Germany. METHODS: From 2010 until 2017, 165 consecutive patients with cervical SCI, initially dependent on a ventilator, were included and weaned discontinuously via tracheal cannula...
January 16, 2018: Spinal Cord
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