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Meng-Lin Liu, Meng-Long Wang, Jing-Jun Lv, Jie Wei, Jun Wan
Adriamycin (ADR) is a chemotherapeutic drug used to treat tumors in a clinical setting. However, its use is limited by a side effect of cardiotoxicity. Glibenclamide (Gli), an inhibitor of mitochondrial ATP-dependent potassium (K-ATP) channels, blocks the cardioprotective effects of mitochondrial K-ATP channel openers and induces apoptosis in rodent pancreatic islet β-cell lines. However, little is known about the role of Gli in ADR-induced cardiotoxicity. The present study was designed to investigate the impact of Gli on ADR-induced cardiotoxicity in rats...
April 2018: Experimental and Therapeutic Medicine
Swetha Sangomla, Mohd Aslam Saifi, Amit Khurana, Chandraiah Godugu
Doxorubicin (DOX) is one of the most commonly used anticancer drugs but its use has been limited due to constraints of cardiotoxic side effects. The precise mechanism underlying cardiotoxicity is not yet fully understood but oxidative stress has been found to be a primary mechanism behind this. In addition, DOX induced cardiotoxicity also shows involvement of proinflammatory cytokines such as IL-6 and TNF-α. Since oxidative stress plays major role in DOX induced cardiotoxicity, different antioxidants have been tried to prevent cardiotoxicity of DOX...
May 2018: Journal of Trace Elements in Medicine and Biology
Nikunjkumar Patel, Oliver Hatley, Alexander Berg, Klaus Romero, Barbara Wisniowska, Debra Hanna, David Hermann, Sebastian Polak
Drug-induced cardiac arrhythmia, especially occurrence of torsade de pointes (TdP), has been a leading cause of attrition and post-approval re-labeling and withdrawal of many drugs. TdP is a multifactorial event, reflecting more than just drug-induced cardiac ion channel inhibition and QT interval prolongation. This presents a translational gap in extrapolating pre-clinical and clinical cardiac safety assessment to estimate TdP risk reliably, especially when the drug of interest is used in combination with other QT-prolonging drugs for treatment of diseases such as tuberculosis...
March 14, 2018: AAPS Journal
Monica Samuel Avila, Silvia Moreira Ayub-Ferreira, Mauro Rogerio de Barros Wanderley Junior, Fatima das Dores Cruz, Sara Michelly Gonçalves Brandão, Vagner Oliveira Carvalho Rigaud, Marilia Higushi-Dos-Santos, Ludhmila Abrahão Hajjar, Roberto Kalil Filho, Paulo Marcelo Hoff, Marina Sahade, Marcela S M Ferrari, Romulo Leopoldo de Paula Costa, Max Senna Mano, Cecilia Beatriz Bittencourt Viana Cruz, Maria Cristina Abduch, Marco Stephan Lofrano Alves, Guilherme Veiga Guimaraes, Victor Sarli Issa, Marcio Sommer Bittencourt, Edimar Alcides Bocchi
BACKGROUND: Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with β-blockers remains controversial. OBJECTIVE: The aim of this prospective, randomized, double-blind, placebo-controlled study was to evaluate the role of carvedilol in preventing ANT cardiotoxicity. METHODS: We randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m2 ) to receive carvedilol or placebo until chemotherapy completion...
March 3, 2018: Journal of the American College of Cardiology
Tanaya Vaidya, Robert M Straubinger, Sihem Ait-Oudhia
PURPOSE: Trastuzumab combined with Doxorubicin (DOX) demonstrates significant clinical activity in human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC). However, emergence of treatment resistance and trastuzumab associated cardiotoxicity remain clinical challenges. In an effort to improve patient outcome, we have developed and evaluated novel tri-functional immunoliposomes (TFIL) that target HER2-receptors on BC cells and CD3-receptors on T-lymphocytes, and deliver DOX...
March 13, 2018: Pharmaceutical Research
Arivalagan Pugazhendhi, Thomas Nesakumar Jebakumar Immanuel Edison, Bharath Kumar Velmurugan, Joe Antony Jacob, Indira Karuppusamy
Doxorubicin (Dox) is a valuable anticancer drug for hematologic and solid tumors. Yet, it can cause multi-organ toxicities in various patients. Since toxicity evaluation is a major criterion to discuss for every experiment, the current mini-review focuses on the toxicity of Dox to multiple organs and suggests the most probable mechanism. Though several mechanisms have been suggested, the role of oxidative stress remains elusive among other mechanisms and remains the most probable mechanism for cardiotoxic effect of Dox...
March 10, 2018: Life Sciences
Esra Metin, Pelin Mutlu, Ufuk Gunduz
BACKGROUND: Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells are also affected, just like cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks. OBJECTIVE: The aim in this study was targeted co-delivery of doxorubicin (Dox) which is an anticancer agent and D-α-Tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS or simply TPGS) to breast cancer cells...
March 13, 2018: Anti-cancer Agents in Medicinal Chemistry
C Vignesh, Madhan Kumar, Ramesh Venkataraman, Senthilkumar Rajagopal, Nagarajan Ramakrishnan, Babu K Abraham
Overdose of cardiovascular medications such as beta blockers and calcium channel blockers cause impaired cardiac contractility, vasoplegia, and/or rhythm disturbances. In addition to conventional management of limiting absorption, increasing elimination and hemodynamic support intravenous (IV) calcium infusion, hyperinsulinemia-euglycemia therapy, glucagon infusion, and IV lipid emulsion have been tried. Extracorporeal circulatory assist device support has been reported as a rescue therapy in overdose refractory to maximal medical therapy...
February 2018: Indian Journal of Critical Care Medicine
Jessica M Scott, Tormod S Nilsen, Dipti Gupta, Lee W Jones
Cardio-oncology is an emerging discipline focused predominantly on the detection and management of cancer treatment-induced cardiac dysfunction (cardiotoxicity), which predisposes to development of overt heart failure or coronary artery disease. The direct adverse consequences, as well as those secondary to anticancer therapeutics, extend beyond the heart, however, to affect the entire cardiovascular-skeletal muscle axis (ie, whole-organism cardiovascular toxicity). The global nature of impairment creates a strong rationale for treatment strategies that augment or preserve global cardiovascular reserve capacity...
March 13, 2018: Circulation
Constance A Mitchell, Subham Dasgupta, Sharon Zhang, Heather M Stapleton, David C Volz
Triphenyl phosphate (TPHP) is an unsubstituted aryl phosphate ester used as a flame retardant and plasticizer within the United States. Using zebrafish as a model, the objectives of this study were to rely on 1) mRNA-sequencing to uncover pathways disrupted following embryonic TPHP exposure and 2) high-content screening to identify nuclear receptor ligands that enhance or mitigate TPHP-induced cardiotoxicity. Based on mRNA-sequencing, TPHP exposure from 24 to 72 h post fertilization (hpf) resulted in a concentration-dependent increase in the number of transcripts significantly affected at 72 hpf, and pathway analysis revealed that five out of nine nuclear receptor pathways were associated with the retinoid X receptor (RXR)...
February 24, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Mehdi Ait Laaradia, Moulay Abdelmonaim El Hidan, Fatimazahra Marhoume, Btissam Bouimeja, Sara Oufquir, Zahra Sokar, Ali Boumezzough, Abderrahman Chait
The present study investigated the toxic effects of B. lienhardi venom, at the histological, hematological, biochemical and motor skill levels following a subcutaneous injection of different doses of venom. The LD50 of B. lienhardi scorpion venom was found to be 0.27 mg/Kg by subcutaneous injection route. The results clearly indicate that B. lienhardi venom induces massive tissue damages in the organs, such as lungs, heart, kidneys and liver together with hematological impairments manifested by decreased levels of both red and white series...
March 8, 2018: Toxicon: Official Journal of the International Society on Toxinology
Ray W Squires, Adam M Shultz, Joerg Herrmann
PURPOSE OF REVIEW: Cancer patients nearly universally experience a decline in quality of life, with fatigue and reduced exercise tolerance as cardinal reflections. A routine exercise program can improve these signs and symptoms as well as overall outcomes. The review provides an updated overview of the field and its translation to clinical practice. RECENT FINDINGS: A wealth of clinical studies have documented the safety and benefits of exercise after and during cancer therapy, and pilot and larger-scale studies are currently ongoing to integrate exercise into the treatment program for cancer patients undergoing active therapy (EXACT pilot, OptiTrain, and TITAN study)...
March 10, 2018: Current Oncology Reports
Lisha Zhao, Xufeng Tao, Yan Qi, Lina Xu, Lianhong Yin, Jinyong Peng
Clinical application of doxorubicin (DOX) is limited because of its cardiotoxicity. Thus, exploration of effective lead compounds against DOX-induced cardiotoxicity is necessary. The aim of the present study was to investigate the effects and possible mechanisms of dioscin against DOX-induced cardiotoxicity. The in vitro model of DOX- treated H9C2 cells and the in vivo models of DOX-treated rats and mice were used in this study. The results showed that discoin markedly increased H9C2 cell viability, decreased the levels of CK, LDH, and improved histopathological and electrocardio- gram changes in rats and mice to protect DOX-induced cardiotoxicity...
March 6, 2018: Redox Biology
Keith Pfannenstiel, Reid Hayward
Though highly effective, doxorubicin (DOX) use is limited by a dose-dependent cardiotoxicity. The purpose of the study was to determine whether resistance training (RT) would protect against DOX-induced cardiac dysfunction and determine if any observed functional preservation is a result of reduced lipid peroxidation or a preservation of the cardiac myosin heavy chain (MHC) isoform distribution. Rats were resistance trained or remained sedentary (SED) for 12 weeks, then treated with 12.5 mg/kg DOX or 0.9% saline...
February 28, 2018: Journal of Cardiovascular Pharmacology
Anzel Bahadır, Ayşe Ceyhan, Özlem Öz Gergin, Betül Yalçın, Menekşe Ülger, Tuğçe Merve Özyazgan, Arzu Yay
OBJECTIVE: Cisplatin (CDDP) has been known to be an effective antineoplastic drug; however, it has a cardiotoxic effect. Curcumin (CMN) and beta-carotene (BC) have been suggested to protect biological systems against CDDP-induced damage. The current study was conducted to evaluate the possible protective roles of CMN and BC on CDDP-induced cardiotoxicity in rat cardiac tissues. METHODS: A total of 49 adult female Wistar albino rats were equally divided into seven groups as follows: control (no medication), sesame oil (1 mg/kg), CDDP (single dose injection two times as once a week, 5 mg/kg/week), BC (100 mg/kg), CDDP+BC (pretreated BC for 30 min before CDDP injection), CMN (200 mg/kg), and CDDP+CMN (pretreated CMN for 30 min before CDDP injection)...
March 2018: Anatolian Journal of Cardiology
Suparna C Clasen, Joyce W Wald
PURPOSE OF REVIEW: We aim to summarize the effect of cancer therapy-related cardiotoxicity on the development of left ventricular (LV) dysfunction. RECENT FINDINGS: We discuss commonly used cancer therapeutics that have the potential for both acute and delayed cardiotoxicity. LV dysfunction from cancer therapies may be found by routine cardiac imaging prior to clinical manifestations of heart failure (HF) and we discuss the current multi-modality approaches for early detection of toxicity with the use of advanced echocardiographic parameters including strain techniques...
March 8, 2018: Current Cardiology Reports
Sebastian Polak, Klaus Romero, Alexander Berg, Nikunjkumar Patel, Masoud Jamei, David Hermann, Debra Hanna
Cardiotoxicity is among the top drug safety concerns, and is of specific interest in tuberculosis, where this is a known or potential adverse event of current and emerging treatment regimens. As there is a need for a tool, beyond the QT interval, to quantify cardiotoxicity early in drug development, an empirical decision tree based classifier was developed to predict the risk of Torsades de pointes (TdP). The cardiac risk algorithm was developed using pseudo-electrocardiogram (ECG) outputs derived from cardiac myocyte electromechanical model simulations of increasing concentrations of 96 reference compounds which represented a range of clinical TdP risk...
March 8, 2018: Journal of Pharmacokinetics and Pharmacodynamics
Michela Pecoraro, Michele Ciccarelli, Antonella Fiordelisi, Guido Iaccarino, Aldo Pinto, Ada Popolo
Doxorubicin (DOXO) administration induces alterations in Connexin 43 (Cx43) expression and localization, thus, inducing alterations in chemical and electrical signal transmission between cardiomyocytes and in intracellular calcium homeostasis even evident after a single administration. This study was designed to evaluate if Diazoxide (DZX), a specific opener of mitochondrial KATP channels widely used for its cardioprotective effects, can fight DOXO-induced cardiotoxicity in a short-time mouse model. DZX (20 mg/kg i...
March 7, 2018: International Journal of Molecular Sciences
Chhanda Bose, Sanjay Awasthi, Rajendra Sharma, Helen Beneš, Martin Hauer-Jensen, Marjan Boerma, Sharda P Singh
Breast cancer is the most common malignancy in women of the Western world. Doxorubicin (DOX) continues to be used extensively to treat early-stage or node-positive breast cancer, human epidermal growth factor receptor-2 (HER2)-positive breast cancer, and metastatic disease. We have previously demonstrated in a mouse model that sulforaphane (SFN), an isothiocyanate isolated from cruciferous vegetables, protects the heart from DOX-induced toxicity and damage. However, the effects of SFN on the chemotherapeutic efficacy of DOX in breast cancer are not known...
2018: PloS One
Mouna Ben Kilani, Soufia Naccache, Rami Tlili, Dorra Mbarek, Salma Longo, Youssef Ben Ameur, Mohamed Rachid Boujnah
Class Ic antiarrythmic overdose is associated with a relatively high mortality. We presenta case report regarding a suicidal intoxication of an 18-year old female with a medical history of Wolff-Parkinson-White syndrome. The preliminary examination highlighted a profound cardiovascular collapse. The electrocardiogram showed a PR interval extended to 360 ms. The QRS complexes were enlarged to 360 ms with a right bundle brunch block appearance associated with left posterior hemibloc. There were repolarization abnormalities such as elevation of the J-point, convex ST segment and biphasic T wave in the right precordial leads ("Brugada-Like ECG pattern")...
June 2017: La Tunisie Médicale
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