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https://www.readbyqxmd.com/read/29161764/mechanism-of-doxorubicin-cardiotoxicity-evaluated-by-integrating-multiple-molecular-effects-into-a-biophysical-model
#1
M Fernandez-Chas, M J Curtis, S A Niederer
BACKGROUND AND PURPOSE: Doxorubicin (DOX) is an effective cancer therapeutic agent but causes therapy-limiting cardiotoxicity. The effects of DOX and its metabolite doxorubicinol (DOXL) on individual channels have been well characterised in isolation. However, it is unknown how the action and interaction of affected channels combine to generate the phenotypic cardiotoxic outcome. We sought to develop an in silico model that links drug effects on channels to action potential duration (APD) and intracellular Ca(2+) concentration in order to address this gap in knowledge...
November 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29157817/cardioprotective-action-of-the-aqueous-extract-of-terminalia-arjuna-bark-against-toxicity-induced-by-doxorubicin
#2
Sarah Bishop, Shi J Liu
BACKGROUND: The aqueous extract of Terminalia arjuna (TA) bark (TAAqE) has been shown to have a direct inotropic effect on ventricular myocytes. Active constituents of TAAqE contain various flavonoids and proanthocyanidins, some of which are known to have antioxidant activities. Whether TAAqE affords a cardioprotective action against oxidative stress (OS) remains unclear. PURPOSE: Increased OS is one of the major mechanisms underlying cardiotoxicity induced by doxorubicin (DOX), a commonly-used anticancer agent...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29157021/gastroparesis-pharmacotherapy-and-cardiac-risk
#3
Per M Hellström, Ahmad Al-Saffar
BACKGROUND: Gastroparesis is characterized by abnormal gastric motility and delayed emptying with symptoms of early satiety, postprandial fullness, bloating, nausea, vomiting and abdominal pain. Pharmacological discovery has been lagging because potential drugs often are associated with abnormalities of electrical conduction of the myocardium due to interaction with cardiac ion channels leading to limited pharmaceutical options for development of new drugs. OBJECTIVE: Addresses the safety of drugs for gastroparesis in terms of cardiotoxicity related to the clinical use of prokinetics and antiemetics...
November 20, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/29155283/comparative-analysis-of-media-effects-on-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-in-proarrhythmia-risk-assessment
#4
Derek Schocken, Jayna Stohlman, Jose Vicente, Dulciana Chan, Dakshesh Patel, Murali Krishna Matta, Vikram Patel, Mathew Brock, Daniel Millard, James Ross, David G Strauss, Ksenia Blinova
INTRODUCTION: Cardiotoxicity assessment using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) forms a key component of the Comprehensive in Vitro Proarrhythmia Assay (CiPA). A potentially impactful factor on iPSC-CM testing is the presence of serum in the experimental media. Generally, serum-free media is used to most accurately reproduce "free" drug concentration. However, caution is needed; drug solubility and cardiomyocyte electrophysiology could be affected by media formulation, potentially impacting interpretation of drug-induced effects...
November 16, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29152646/naringin-protects-myocardial-cells-from-doxorubicin%C3%A2-induced-apoptosis-partially-by-inhibiting-the-p38mapk-pathway
#5
Chun-Yan Jian, Han-Bin Ouyang, Xian-Hong Xiang, Jia-Li Chen, Yong-Xin Li, Xin Zhou, Jin-Yang Wang, Yang Yang, En-Yi Zhong, Wen-Hua Huang, Hong-Wu Zhang
Doxorubicin (DOX) has been widely used to treat cancers as a first‑line antitumor drug. However, it causes severe, irreversible, dose‑dependent cardiotoxicity. To evaluate the protective effects of naringin (NRG) on cardiotoxicity, the authors investigated the molecular mechanism of the p38MAPK signaling pathway. H9c2 cells were treated for 24 h by using 5 µmol/l DOX without or with being pretreated by 1 µM NRG for 150 min or by 3 µM SB203580 for 60 min. Cell viability was detected by cell counting kit‑8 assay...
October 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29152433/to-dab-or-not-to-dab-rising-concerns-regarding-the-toxicity-of-cannabis-concentrates
#6
EDITORIAL
Saeed K Alzghari, Victor Fung, Shannon S Rickner, Liza Chacko, Steven W Fleming
Cannabis use is steadily rising in the United States. As the popularity of marijuana rises, new varieties of cannabis-related products are becoming available. Dabs are cannabis concentrates gaining notoriety for their significant amounts of tetrahydrocannabinol (THC) that are ultimately vaporized and inhaled for their effect. Herein, we provide an overview of recent cases of dabbing to bring awareness to the clinicians, of the significant adverse effects associated with dabs including psychosis, neurotoxicity, and cardiotoxicity...
September 11, 2017: Curēus
https://www.readbyqxmd.com/read/29152091/fibroblast-growth-factor-2-mediated-protection-of-cardiomyocytes-from-the-toxic-effects-of-doxorubicin-requires-the-mtor-nrf-2-ho-1-pathway
#7
Navid Koleini, Barbara E Nickel, Jie Wang, Zeinab Roveimiab, Robert R Fandrich, Lorrie A Kirshenbaum, Peter A Cattini, Elissavet Kardami
Background: Cardiotoxic side effects impose limits to the use of anti-tumour chemotherapeutic drugs such as doxorubicin (Dox). There is a need for cardioprotective strategies to prevent the multiple deleterious effects of Dox. Here, we examined the ability of administered fibroblast growth factor-2 (FGF-2), a cardioprotective protein that is synthesized as high and low molecular weight (Hi-, Lo-FGF-2) isoforms, to prevent Dox-induced: oxidative stress; cell death; lysosome dysregulation; and inactivation of potent endogenous protective pathways, such as the anti-oxidant/detoxification nuclear factor erythroid-2-related factor (Nrf-2), heme oxygenase-1 (HO-1) axis...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151290/-early-detection-of-the-cardiotoxicity-induced-by-chemotherapy-drug-through-two-dimensional-speckle-tracking-echocardiography-combined-with-high-sensitive-cardiac-troponin-t
#8
W Wang, Y Kang, X H Shu, X D Shen, B He
Objective: To investigate the clinical value of two-dimensional speckle tracking echocardiography(2D-STE) combined with high-sensitive cardiac troponin T (hs-cTnT) in early detection of the cardiotoxicity induced by chemotherapy drug. Methods: Seventy-five non-Hodgkin's lymphoma patients who received the CHOP regimen were recruited in this study. Conventional echocardiography and 2D-STE were performed on these patients before chemotherapy, the second day after the third course of chemotherapy (during chemotherapy) and the second day after the last course of chemotherapy (after chemotherapy)...
November 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/29147934/an-outbreak-of-poisoning-by-kalanchoe-blossfeldiana-in-cattle-in-northeastern-brazil
#9
Fábio S Mendonça, Naiara C F Nascimento, Valdir M Almeida, Thaiza C Braga, Daniele P Ribeiro, Hisadora A S Chaves, Givaldo B Silva Filho, Franklin Riet-Correa
In the world, Kalanchoe species are primarily ornamentals and houseplants, but some have escaped cultivation and can be found in the field. In Latin America, there are no reports of spontaneous poisoning by Kalanchoe species in animals. This study aimed to describe the epidemiological, clinical, and pathological aspects of an outbreak of poisoning by Kalanchoe blossfeldiana in cattle in the semiarid region of Pernambuco, Brazil. Epidemiological and clinical data were obtained from the owner and veterinarian during technical visits...
November 16, 2017: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/29145955/cardiovascular-complications-of-cancer%C3%A2-therapy-best-practices-in-diagnosis-prevention-and-management-part-2
#10
REVIEW
Hui-Ming Chang, Tochukwu M Okwuosa, Tiziano Scarabelli, Rohit Moudgil, Edward T H Yeh
In this second part of a 2-part review, we will review cancer or cancer therapy-associated systemic and pulmonary hypertension, QT prolongation, arrhythmias, pericardial disease, and radiation-induced cardiotoxicity. This review is based on a MEDLINE search of published data, published clinical guidelines, and best practices in major cancer centers. Newly developed targeted therapy can exert off-target effects causing hypertension, thromboembolism, QT prolongation, and atrial fibrillation. Radiation therapy often accelerates atherosclerosis...
November 14, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29145932/lipid-emulsion-more-than-reversing-bupivacaine-cardiotoxicity-potential-organ-protection
#11
Negar Motayagheni, Sheshanna Phan, Ala Nozari, Anthony Atala
Efforts to develop a treatment for bupivacaine cardiotoxicity led to the discovery that Intralipid, a popular brand of intravenous lipid emulsion, could be used not only as an effective treatment for anesthetic-induced cardiac arrest, but also as a means of reversing many other toxicities. Contradictory data exist regarding the mechanism of action of lipid emulsion, a combination of fatty acids traditionally used in parenteral nutrition. Some researchers attribute the effects to lipophilicity and the individual characteristics of the lipids, while other data demonstrate a direct empowering mechanism through cellular upstream and downstream pathways...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29142197/proteotoxicity-in-cardiac-amyloidosis-amyloidogenic-light-chains-affect-the-levels-of-intracellular-proteins-in-human-heart-cells
#12
Esther Imperlini, Massimiliano Gnecchi, Paola Rognoni, Eduard Sabidò, Maria Chiara Ciuffreda, Giovanni Palladini, Guadalupe Espadas, Francesco Mattia Mancuso, Margherita Bozzola, Giuseppe Malpasso, Veronica Valentini, Giuseppina Palladini, Stefania Orrù, Giovanni Ferraro, Paolo Milani, Stefano Perlini, Francesco Salvatore, Giampaolo Merlini, Francesca Lavatelli
AL amyloidosis is characterized by widespread deposition of immunoglobulin light chains (LCs) as amyloid fibrils. Cardiac involvement is frequent and leads to life-threatening cardiomyopathy. Besides the tissue alteration caused by fibrils, clinical and experimental evidence indicates that cardiac damage is also caused by proteotoxicity of prefibrillar amyloidogenic species. As in other amyloidoses, the damage mechanisms at cellular level are complex and largely undefined. We have characterized the molecular changes in primary human cardiac fibroblasts (hCFs) exposed in vitro to soluble amyloidogenic cardiotoxic LCs from AL cardiomyopathy patients...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142174/evaluation-system-for-arrhythmogenic-potential-of-drugs-using-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-and-gene-expression-analysis
#13
Arisa Higa, Hirotaka Hoshi, Yuka Yanagisawa, Emi Ito, Gaku Morisawa, Jun-Ichi Imai, Shinya Watanabe, Motoki Takagi
In recent years, human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) have been widely used to develop evaluation systems for drug cardiotoxicity, including the arrhythmia caused by QT prolongation. To accurately assess the arrhythmogenic potential of drugs, associated with QT prolongation, we developed an evaluation system using hiPS-CMs and gene expression analysis. hiPS-CMs were treated with 8 arrhythmogenic and 17 non-arrhythmogenic drugs at several concentrations for 24 hr to comprehensively analyze gene expression...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29141899/atypical-g-protein-%C3%AE-5-promotes-cardiac-oxidative-stress-apoptosis-and-fibrotic-remodeling-in-response-to-multiple-cancer-chemotherapeutics
#14
Biswanath Maity, Sreemoyee Chakraborti, Arnab Pramanick, Sudipta Saha, Somnath Singha Roy, Arnab Ray Chaudhuri, Madhusudan Das, Sujoy Ghosh, Adele Stewart
The clinical use of multiple classes of cancer chemotherapeutics is limited by irreversible, dose-dependent, and sometimes life-threatening cardiotoxicity. We report here that, though distinct in their mechanisms of action, doxorubicin, paclitaxel, and 5-FU all induce rapid and robust upregulation of atypical G protein Gβ5 in the myocardium, correlating with oxidative stress, myocyte apoptosis, and the accumulation of pro-inflammatory and pro-fibrotic cytokines. In ventricular cardiac myocytes (VCM), Gβ5 deficiency provided substantial protection against the cytotoxic actions of chemotherapeutics, including reductions in oxidative stress and simultaneous attenuation of ROS-dependent activation of the ATM and CaMKII pro-apoptotic signaling cascades...
November 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/29140569/single-cell-functional-analysis-of-stem-cell-derived-cardiomyocytes-on-micropatterned-flexible-substrates
#15
Jan David Kijlstra, Dongjian Hu, Peter van der Meer, Ibrahim J Domian
Human pluripotent stem-cell derived cardiomyocytes (hPSC-CMs) hold great promise for applications in human disease modeling, drug discovery, cardiotoxicity screening, and, ultimately, regenerative medicine. The ability to study multiple parameters of hPSC-CM function, such as contractile and electrical activity, calcium cycling, and force generation, is therefore of paramount importance. hPSC-CMs cultured on stiff substrates like glass or polystyrene do not have the ability to shorten during contraction, making them less suitable for the study of hPSC-CM contractile function...
November 15, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/29135673/myocardial-cobalt-levels-are-elevated-in-the-setting-of-total-hip-arthroplasty
#16
Cody C Wyles, T Carson Wright, Melanie C Bois, Md Shahrier Amin, Ahmed Fayyaz, Sarah M Jenkins, Saranya P Wyles, Patrick L Day, David L Murray, Robert T Trousdale, Nandan S Anavekar, William D Edwards, Joseph J Maleszewski
BACKGROUND: Arthroplasty implants commonly contain elemental metal that may undergo wear-related release. Recently, cases of hip implant-associated myocardial injury have been reported. However, we are not aware of any previous study that has systematically measured myocardial metal levels or examined the relationship with total hip arthroplasty (THA). METHODS: Archives of our institution were queried for autopsies of individuals who had undergone THA between 1990 and 2013...
November 15, 2017: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/29133306/quaking-inhibits-doxorubicin-mediated-cardiotoxicity-through-regulation-of-cardiac-circular-rna-expression
#17
Shashi K Gupta, Ankita Garg, Christian Bär, Shambhabi Chatterjee, Ariana Foinquinos, Hendrik Milting, Katrin Streckfuss-Bömeke, Jan Fiedler, Thomas Thum
Rationale: RNA-binding proteins (RBPs) have been described to be expressed and regulated in various organs including the heart. Little is known about the role of RBPs in heart failure induced by the chemotherapy drug doxorubicin and their interaction with circular RNAs. Objective: We aimed to identify key RBPs involved in doxorubicin-mediated heart failure and to elucidate their function. Methods and Results: Global transcriptome profiling from murine myocardium exposed to doxorubicin identified five differentially expressed RBPs...
November 13, 2017: Circulation Research
https://www.readbyqxmd.com/read/29133031/chloroquine-upregulates-trail-trailr2-expression-and-potentiates-doxorubicin-anti-tumor-activity-in-thioacetamide-induced-hepatocellular-carcinoma-model
#18
Sahar A Helmy, Mohamed El-Mesery, Amro El-Karef, Laila A Eissa, Amal M El Gayar
Impaired apoptosis and systemic toxicity of chemotherapeutic drugs make cancer treatment suboptimal. Thus, there is urgency for drug repurposing which facilitates discovery of safe and effective combination therapy. This study aimed to evaluate chloroquine's (CQ) ability to trigger TRAIL/TRAILR2 apoptotic pathway in thioacetamide (TAA)-induced hepatocellular carcinoma (HCC) either alone or in combination with doxorubicin (DOX). Moreover, its ability to attenuate DOX-induced cardiotoxicity was investigated. TAA was injected in male Sprague Dawely rats (200 mg/kg; ip; 2 times/week) for 16 weeks...
November 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29131861/delivery-of-epirubicin-via-slow-infusion-as-a-strategy-to-mitigate-chemotherapy-induced-cardiotoxicity
#19
Fang Yang, Qiao Lei, Lu Li, Jian Chang He, Jiajia Zeng, Chunxiang Luo, Sai-Ching Jim Yeung, Runxiang Yang
BACKGROUND: Continuous infusion of doxorubicin has been a strategy to reduce cardiotoxicity. Epirubicin is another anthracycline in common clinical use. However, evidence is lacking regarding whether this strategy can reduce cardiotoxicity of epirubicin without compromising antineoplastic efficacy. DESIGN AND METHODS: Healthy rats were randomized into groups: epirubicin (8 mg/kg) delivered intraperitoneally via micro osmotic pumps (MOP), epirubicin (8 mg/kg) by intraperitoneal (IP) bolus injection, and placebo control...
2017: PloS One
https://www.readbyqxmd.com/read/29129433/nanoparticulate-specific-effects-of-silver-on-teleost-cardiac-contractility
#20
Neal Ingraham Callaghan, Kenneth Javier Williams, J Craig Bennett, Tyson James MacCormack
Silver nanoparticles (nAg), due to their biocidal properties, are common in medical applications and are used in more consumer products than any other engineered nanomaterial. This growing abundance, combined with their ability to translocate across the epithelium and bioaccumulate, suggests that internalized nAg may present a risk of toxicity to many organisms in the future. However, little experimentation has been devoted to cardiac responses to acute nAg exposure, even though nAg is known to disrupt ion channels even when ionic Ag(+) does not...
November 9, 2017: Environmental Pollution
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