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Cardiac Toxicity

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https://www.readbyqxmd.com/read/28546047/an-impedance-based-approach-using-human-ipsc-derived-cardiomyocytes-significantly-improves-in-vitro-prediction-of-in-vivo-cardiotox-liabilities
#1
Bryan Koci, Gregory Luerman, Anika Duenbostell, Ralf Kettenhofen, Heribert Bohlen, Luke Coyle, Brian Knight, Warren Ku, Walter Volberg, Joseph R Woska, Martha P Brown
Current in vitro approaches to cardiac safety testing typically focus on mechanistic ion channel testing to predict in vivo proarrhythmic potential. Outside of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, structural and functional cardiotoxicity related to chronic dosing effects are of great concern as these effects can impact compound attrition. Development and implementation of an in vitro cardiotoxicity screening platform that effectively identifies these liabilities early in the discovery process should reduce costly attrition and decrease preclinical development time...
May 22, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28545322/cardiovascular-events-during-carfilzomib-therapy-for-relapsed-myeloma-practical-management-aspects-from-two-case-studies
#2
Andrzej J Jakubowiak, Jeanne M DeCara, Khalid Mezzi
Objectives and importance: Patients with multiple myeloma (MM) have an increased risk of cardiovascular comorbidities due to disease burden and treatment-related risk factors. Proteasome inhibitors, including bortezomib and carfilzomib, are effective and generally well tolerated anti-MM agents. However, cardiovascular-related toxicities have been reported with this class of agents, the mechanisms of which are not fully understood. We discuss the practical management of cardiovascular events during carfilzomib therapy for relapsed MM...
May 25, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28542037/long-term-use-of-pegylated-liposomal-doxorubicin-to-a-cumulative-dose-of-4600%C3%A2-mg-m2-in-recurrent-ovarian-cancer
#3
Adam Pendlebury, Robert DeBernardo, Peter G Rose
Pegylated liposomal doxorubicin (PLD) is used widely in gynecologic oncology and other oncology disciplines. Native doxorubicin use is associated with the potential for significant toxicity. Cardiac toxicity in particular limits lifetime dose. PLD has not been shown to be associated with clinical cardiac toxicity. We report on the long-term use of PLD in a patient with recurrent high-grade serous ovarian cancer to a lifetime dose of 4600 mg/m. This therapy was associated with long-term stable disease, good performance status, and minimal adverse effects...
May 24, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28539741/potential-roles-of-kleinhovia-hospita-l-leaf-extract-in-reducing-doxorubicin-acute-hepatic-cardiac-and-renal-toxicities-in-rats
#4
Yulia Yusrini Djabir, M Aryadi Arsyad, Sartini Sartini, Subehan Lallo
BACKGROUND: Doxorubicin (DOX) is a potent chemotherapy agent; however, its use may lead to cardiac, hepatic, and renal dysfunction. Kleinhovia hospita L extract contains antioxidant compounds that have been shown to reduce chemical-induced hepatotoxicity. OBJECTIVES: This study aimed to examine the protective effects of Kleinhovia sp. extract to reduce DOX acute toxicities. MATERIALS AND METHODS: Thirty male rats were assigned to the following groups: Group I as controls, Group II was given DOX i...
April 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/28538107/local-anesthetics-systemic-toxicity-association-with-exparel-bupivacaine-liposome-a-pharmacovigilance-evaluation
#5
Nitish Aggarwal
BACKGROUND: Local Anesthetic Systemic Toxicity (LAST) is a rare life threatening complication usually from intra-arterial or intravenous injection leading to systemic absorption of regional anesthesia drug. The objective of this research was to statistically quantify the association between Exparel (bupivacaine liposome) injectable suspension and LAST. METHODS: Adverse Event Reporting System database of FDA, which houses public and industry submitted adverse event case reports, was queried and analyzed to quantify the passive pharmacovigilance signal for Local Anesthetic Systemic Toxicity as associated with use of bupivacaine Liposome...
May 24, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28533750/characterization-of-cardiovascular-alterations-induced-by-different-chronic-cisplatin-treatments
#6
Esperanza Herradón, Cristina González, José A Uranga, Raquel Abalo, Ma I Martín, Visitacion López-Miranda
In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28531278/cardiovascular-toxic-effects-of-targeted-cancer-therapy
#7
Kazuko Tajiri, Kazutaka Aonuma, Ikuo Sekine
Over the past decade, there has been a major shift in chemotherapy from non-specific cytotoxic drugs to molecular targeted drug therapies. As more molecular targeted therapies are developed, new types of cardiovascular toxicities induced by targeted therapies are a growing problem. Cardiotoxicity induced by the human epidermal growth factor receptor-2 inhibitor trastuzumab manifests as decreased left ventricular ejection fraction. In contrast to anthracycline treatment, most cardiac events occur during trastuzumab treatment, but are reversed quickly when treatment is interrupted and cardiac intervention is established...
May 20, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28527782/protective-roles-of-bioactive-peptides-during-ischemia-reperfusion-injury-from-bench-to-bedside
#8
REVIEW
Dongdong Wu, Jun Wang, Honggang Wang, Ailing Ji, Yanzhang Li
Ischemia-reperfusion (I/R) is a well-known pathological condition which may lead to disability and mortality. I/R injury remains an unresolved and complicated situation in a number of clinical conditions, such as cardiac arrest with successful reanimation, as well as ischemic events in brain and heart. Peptides have many attractive advantages which make them suitable candidate drugs in treating I/R injury, such as low toxicity and immunogenicity, good solubility property, distinct tissue distribution pattern, and favorable pharmacokinetic profile...
May 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28526264/celecoxib-aggravates-cardiac-apoptosis-in-l-name-induced-pressure-overload-model-in-rats-immunohistochemical-determination-of-cardiac-caspase-3-mcl-1-bax-and-bcl-2
#9
Sarah M Mosaad, Sawsan A Zaitone, Abdelazim Ibrahim, Amani A El-Baz, Dina M Abo-Elmatty, Yasser M Moustafa
The mechanism of celecoxib cardiovascular adverse events was earlier investigated; yet in-depth investigations are needed to assess the involvement of its pro-apoptotic effect throughout this process. An in-vivo chronic rat model of pressure overload employing Nʷ-nitro-l-arginine methyl ester (L-NAME) was tested at different time intervals to ensure the occurrence of persistent myocardial apoptosis along with pressure overload. Seven groups of male Wistar rats were assigned as (i) distilled water; (ii-iv) L-NAME (60 mg/kg) for 6, 12 or 16 weeks; (v-vii) L-NAME [16 weeks] + celecoxib (25, 50 or 100 mg/kg), from week 13 to week 16...
May 16, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28522573/lenalidomide-melphalan-dexamethasone-in-newly-diagnosed-patients-with-al-amyloidosis-results-of-a-prospective-phase-2-study-with-long-term-follow-up
#10
Ute Hegenbart, Tilmann Bochtler, Axel Benner, Natalia Becker, Christoph Kimmich, Arnt V Kristen, Jörg Beimler, Ernst Hund, Markus Zorn, Anja Freiberger, Marianne Gawlik, Hartmut Goldschmidt, Dirk Hose, Anna Jauch, Anthony D Ho, Stefan O Schönland
Chemotherapy in light chain amyloidosis aims to normalize the involved free light chain in serum, which leads to an improvement or at least stabilization of organ function in most responding patients. We performed a prospective single center phase 2 trial with 50 untreated patients not eligible for high-dose treatment. The treatment schedule comprised 6 cycles of oral lenalidomide, melphalan and dexamethasone every 4 weeks. After 6 months complete remission was achieved in 9 patients (18%), very good partial remission in 16 (32%) and partial response in 9 (18%)...
May 18, 2017: Haematologica
https://www.readbyqxmd.com/read/28521972/coronary-vasospasm-associated-with-5-fluorouracil-chemotherapy-cardiac-toxicity-or-cardiac-hypersensitivity
#11
Nicholas G Kounis, Ioanna Koniari, Nicholas Patsouras, Nicholas Koutsogiannis, Dimitrios Velissaris, George Soufras, George Hahalis
No abstract text is available yet for this article.
May 12, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28521150/the-effects-of-copper-oxide-nanoparticles-on-dorsoventral-patterning-convergent-extension-and-neural-and-cardiac-development-of-zebrafish
#12
Jia Xu, Qiuping Zhang, Xu Li, Sihui Zhan, Lifeng Wang, Dongyan Chen
Currently, nanoparticles are widely used in biomedicine and industry. CuO nanoparticles (CuO-NPs) are versatile materials in our daily life and their toxicity has drawn extensive attention. In this study, we concentrate on the effect of CuO-NPs on early zebrafish development. The results reveal that CuO-NPs can induce abnormal phenotypes of a smaller head and eyes and delayed epiboly. The gene expression pattern shows that CuO-NPs spatially narrow the expression of dorsal genes chordin and goosecoid and alter the expression of dlx3, ntl and hgg which are related to the cell migration of gastrulation...
May 4, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28516409/survival-after-severe-rhabdomyolysis-following-monensin-ingestion
#13
Michela Blain, Alexander Garrard, Robert Poppenga, Betty Chen, Matthew Valento, Melissa Halliday Gittinger
INTRODUCTION: Monensin is a veterinary antibiotic with a narrow therapeutic window that has led to lethal intoxication in many animal species. Only two prior cases of human toxicity have been reported, both fatal. We present the first case of survival from severe toxicity following monensin ingestion. CASE: A 58-year-old man presented with 8 days of vomiting and abdominal pain. Due to delusions of central nervous system toxoplasmosis, he ingested 300 mg of monensin...
May 17, 2017: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
https://www.readbyqxmd.com/read/28515029/tolvaptan-utilization-in-children-with-chronic-hyponatremia-due-to-inappropriate-antidiuretic-hormone-secretion-siadh-three-case-reports-and-review-of-the-literature
#14
Gerdi Tuli, Daniele Tessaris, Luisa De Sanctis, Patrizia Matarazzo
Hyponatremia is the most common electrolyte disorder among hospitalized patients and it is sometimes considered as a poor outcome predictor. Its correction is thus indicated, even in asymptomatic patients. The conventional treatment is represented by fluid restriction in presence of euvolemia or hypervolemia; whereas loop diuretics are used in some hypervolemic conditions (cardiac heart failure, liver cirrhosis and nephrotic syndrome) and intravenous isotonic or hypertonic solution are administered in hypovolemic conditions...
May 17, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/28510119/genetic-epidemiology-of-titin-truncating-variants-in-the-etiology-of-dilated-cardiomyopathy
#15
REVIEW
Ali M Tabish, Valerio Azzimato, Aris Alexiadis, Byambajav Buyandelger, Ralph Knöll
Heart failure (HF) is a complex clinical syndrome defined by the inability of the heart to pump enough blood to meet the body's metabolic demands. Major causes of HF are cardiomyopathies (diseases of the myocardium associated with mechanical and/or electrical dysfunction), among which the most common form is dilated cardiomyopathy (DCM). DCM is defined by ventricular chamber enlargement and systolic dysfunction with normal left ventricular wall thickness, which leads to progressive HF. Over 60 genes are linked to the etiology of DCM...
May 5, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28508834/a-dosimetric-analysis-of-cardiac-dose-with-or-without-active-breath-coordinator-moderate-deep-inspiratory-breath-hold-in-left-sided-breast-cancer-radiotherapy
#16
Beena Kunheri, Sanketh Kotne, Sneha S Nair, Dinesh Makuny
BACKGROUND AND AIM: Cardiac toxicity is a major concern for left breast tangential field irradiation. The left ventricle and left anterior descending (LAD) artery are suggested to be radiosensitive and radiation to these structures leads to late lethal cardiotoxicity. Moderate deep inspiration breath hold (mDIBH) during radiation treatment delivery helps in reducing the cardiac dose. This study compares dosimetric parameters of heart with and without active breath coordinator (ABC) mDIBH during tangential field breast cancer radiation...
January 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28507459/spironolactone-ameliorates-the-cardiovascular-toxicity-induced-by-concomitant-trastuzumab-and-thoracic-radiotherapy
#17
Guler Yavas, Esin Celik, Cagdas Yavas, Cagdas Elsurer, Rengin Elsurer Afsar
AIM: We aimed to evaluate impact of spironolactone (S) on cardiovascular toxicity of concomitant use of radiotherapy (RT) and trastuzumab (T). BACKGROUND: S, an aldosterone receptor antagonist, is known to ameliorate the cardiac damage. S ameliorates anthracycline -induced cardiotoxicity, there is no data regarding to effect of S on both T and radiation-induced cardiotoxicity. MATERIALS/METHODS: Eighty rats were divided into eight groups: group (G) 1 was defined as control group...
July 2017: Reports of Practical Oncology and Radiotherapy
https://www.readbyqxmd.com/read/28506439/clinical-review-loperamide-toxicity
#18
REVIEW
Peter E Wu, David N Juurlink
Loperamide is a nonprescription opioid widely used for the treatment of diarrhea. Although it is relatively safe at therapeutic doses, increasing reports describe its misuse and abuse at very high doses either for euphoric effects or to attenuate symptoms of opioid withdrawal. Life-threatening loperamide toxicity can result from the relatively new clinical syndrome of loperamide-induced cardiac toxicity. These patients are often young and may present in cardiac arrest or with unheralded, recurrent syncope in conjunction with ECG abnormalities, including marked QT-interval prolongation, QRS-interval widening, and ventricular dysrhythmias...
May 13, 2017: Annals of Emergency Medicine
https://www.readbyqxmd.com/read/28503984/the-genotoxic-effect-of-oxcarbazepine-on-mice-blood-lymphocytes
#19
Huma Akbar, Ajmal Khan, Imdadullah Mohammadzai, Muhammad Khisroon, Ilham Begum
This study was conducted to assess the amount of DNA damage caused by Oxcarbazepine (OXC) through single cell gel electrophoresis (SCGE) technique/comet assay. OXC derived from dibenzazepine series is an effective second generation antiepileptic drug (AED) for both children and adults. Side effects like genotoxic effects of AEDs are of prime importance resulting from toxic metabolites, free radicals and reactive oxygen species (ROS). Forty Eight adult male Bagg's albino mice (BALB/c) were randomly classified into eight groups, each comprising of six animals...
May 15, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/28503840/a-critical-note-on-treatment-of-a-severe-diltiazem-intoxication-high-dose-calcium-and-glucagon-infusions
#20
N M Van Veggel, G J Van der Veen, T C Jansen, E M Westerman
The morbidity and mortality of a severe calcium channel blocker intoxication is high due to serious toxic cardiac effects. Its treatment is supported by low-quality evidence from heterogeneous literature. We describe a case of a severe diltiazem intoxication and critically appraise the efficacy and role of high-dose calcium and glucagon infusions. A 53-year-old woman was admitted to the emergency department with a cardiogenic shock with complete AV block, not responding to atropine, isoprenaline and an external pacemaker...
May 15, 2017: Basic & Clinical Pharmacology & Toxicology
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