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https://www.readbyqxmd.com/read/28729311/a-review-of-rate-control-in-atrial-fibrillation-and-the-rationale-and-protocol-for-the-rate-af-trial
#1
Dipak Kotecha, Melanie Calvert, Jonathan J Deeks, Michael Griffith, Paulus Kirchhof, Gregory Yh Lip, Samir Mehta, Gemma Slinn, Mary Stanbury, Richard P Steeds, Jonathan N Townend
BACKGROUND AND OBJECTIVE: Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article , we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity...
July 20, 2017: BMJ Open
https://www.readbyqxmd.com/read/28727807/digoxin-reveals-a-functional-connection-between-hiv-1-integration-preference-and-t-cell-activation
#2
Alexander Zhyvoloup, Anat Melamed, Ian Anderson, Delphine Planas, Chen-Hsuin Lee, Janos Kriston-Vizi, Robin Ketteler, Andy Merritt, Jean-Pierre Routy, Petronela Ancuta, Charles R M Bangham, Ariberto Fassati
HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28720385/differences-of-lipid-membrane-modulation-and-oxidative-stress-by-digoxin-and-21-benzylidene-digoxin
#3
Lilian Nd Silva, Silmara Lg Alves, Jessica Venugopal, Vanessa F Cortes, Herica L Santos, José Afp Villar, Leandro A Barbosa
Cardiotonic steroids (CTS) are compounds which bind to the Na,K-ATPase, leading to its inhibition and in some cases initiating signaling cascades. Long utilized as a treatment for congestive heart disease, CTS have more recently been observed to inhibit proliferation and cause apoptosis in several cancer cell lines. A synthetic derivative of the CTS digoxin, called 21-benzylidene digoxin (21-BD), activates the Na,K-ATPase rather than cause its inhibition, as its parent compound does. Here, the mechanism behind the unique effects of 21-BD are further explored...
July 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28720014/the-impact-of-intrauterine-treatment-on-fetal-tachycardia-a-nationwide-survey-in-japan
#4
Keiko Ueda, Yasuki Maeno, Takekazu Miyoshi, Noboru Inamura, Motoyoshi Kawataki, Mio Taketazu, Masaki Nii, Akiko Hagiwara, Hitoshi Horigome, Makio Shozu, Wataru Shimizu, Satoshi Yasukochi, Hitoshi Yoda, Isao Shiraishi, Heima Sakaguchi, Shinji Katsuragi, Haruhiko Sago, Tomoaki Ikeda
OBJECTIVES: To investigate the clinical course of fetal tachycardia and analyze the impact of intrauterine treatment on the postnatal treatment and patient outcomes. STUDY DESIGN: This was a retrospective review of cases of fetal tachycardia that occurred from 2004 to 2006. Data were collected from questionnaires that were sent to all 750 secondary or tertiary perinatal care centers in Japan. RESULTS: Eighty-two cases (14 with fetal hydrops) were analyzed (supraventricular tachycardia [SVT], n = 52; atrial flutter [AFL], n = 23; and ventricular tachycardia, n = 7)...
July 19, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28711269/development-of-an-isothermal-amplification-based-assay-for-the-rapid-visual-detection-of-salmonella-bacteria
#5
Hai-Bin Liu, Yu-Xuan Zang, Xin-Jun Du, Ping Li, Shuo Wang
The efficient and timely detection of pathogens is a major concern worldwide. The aim of this study was to establish a rapid detection method for Salmonella bacteria in food samples to facilitate timely treatment. Widely used detection methods currently include culture-based methods and PCR-based methods. The former are time consuming, requiring 2 to 3 d, whereas the latter have higher accuracy but are typically complicated, requiring expertise and expensive instruments. In this study, a sensitive and rapid approach for the visual and point-of-use detection of Salmonella bacteria based on recombinase polymerase amplification (RPA) and a lateral-flow (LF) nucleic acid strip was established...
July 12, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28706279/elimination-of-undifferentiated-human-embryonic-stem-cells-by-cardiac-glycosides
#6
Yu-Tsen Lin, Cheng-Kai Wang, Shang-Chih Yang, Shu-Ching Hsu, Hsuan Lin, Fang-Pei Chang, Tzu-Chien Kuo, Chia-Ning Shen, Po-Ming Chiang, Michael Hsiao, Frank Leigh Lu, Jean Lu
An important safety concern in the use of human pluripotent stem cells (hPSCs) is tumorigenic risk, because these cells can form teratomas after an in vivo injection at ectopic sites. Several thousands of undifferentiated hPSCs are sufficient to induce teratomas in a mouse model. Thus, it is critical to remove all residue-undifferentiated hPSCs that have teratoma potential before the clinical application of hPSC-derived cells. In this study, our data demonstrated the cytotoxic effects of cardiac glycosides, such as digoxin, lanatoside C, bufalin, and proscillaridin A, in human embryonic stem cells (hESCs)...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701029/high-risk-prescribing-in-an-irish-primary-care-population-trends-and-variation
#7
Catherine J Byrne, Caitriona Cahir, Carmel Curran, Kathleen Bennett
AIMS: To examine the prevalence of high-risk prescribing (HRP) in community-dwelling adults in Ireland from 2011-2015 using consensus-validated indicators, factors associated with HRP, and variation in HRP between general practitioners (GPs) and dispensing of high-risk prescriptions between pharmacies. METHODS: A repeated cross-sectional national pharmacy claims database study. Prescribing indicators were based on those developed in formal consensus studies and applicable to pharmacy claims data...
July 12, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28693242/bufalin-sensitizes-human-bladder-carcinoma-cells-to-trail-mediated-apoptosis
#8
Kyung-Hwa Kang, Min Ho Han, Jin-Woo Jeong, Cheol Park, Sang-Hyup Lee, Hai Woong Lee, Sang Hoon Hong, Yung Hyun Choi, Su Hyun Hong
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, has garnered interest as it is relatively non-toxic to normal cells, but selectively induces apoptotic cell death in multiple types of transformed or malignant cells. Bufalin is the major digoxin-like immunoreactive component of Sum Su, which is obtained from the skin and parotid venom gland of the toad. Bufalin is known to inhibit cell proliferation and induce apoptosis in a variety of cancer cells. The present study investigated whether bufalin promoted TRAIL-induced apoptotic cell death...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28692216/-digoxin-and-atrial-fibrillation-in-2016
#9
Sarah Théone, Sebastian Carballo, David Carballo, Christophe Marti
Various properties of digoxin have been exploited for decades, amongst which are its positive inotropy used in the treatment of heart failure, and its vagotonic effect used to slow ventricular response to atrial fibrillation. Pharmacologic properties of digoxin are however characterised by a narrow therapeutic interval, and recent observational studies suggest a potential association with increased mortality in patients with atrial fibrillation. As a result and because of available alternative therapeutic strategies, current guidelines do not recommend digoxin as first line treatment of atrial fibrillation...
October 19, 2016: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28688145/therapeutic-concentrations-of-digitoxin-inhibit-endothelial-focal-adhesion-kinase-and-angiogenesis-induced-by-diverse-growth-factors
#10
Annalisa Trenti, Elisabetta Zulato, Lorenza Pasqualini, Stefano Indraccolo, Chiara Bolego, Lucia Trevisi
BACKGROUND AND PURPOSE: Cardiac glycosides are Na(+) /K(+) -ATPases inhibitors used to treat congestive heart failure and cardiac arrhythmias. Epidemiological studies indicate that patients on digitalis therapy are more protected from cancer. Evidence of a selective cytotoxicity against cancer cells has suggested their potential use as anticancer drugs. The effect on angiogenesis of clinically used cardiac glycosides has not been extensively explored. EXPERIMENTAL APPROACH: We studied the effect of digoxin, digitoxin and ouabain on early events of the angiogenic process in human umbilical vein endothelial cells (HUVEC)...
July 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28685495/effects-of-metformin-and-furosemide-on-rosuvastatin-pharmacokinetics-in-healthy-volunteers-implications-for-their-use-as-probe-drugs-in-a-transporter-cocktail
#11
Peter Stopfer, Thomas Giessmann, Kathrin Hohl, Ashish Sharma, Naoki Ishiguro, Mitchell E Taub, Arvid Jungnik, Dietmar Gansser, Thomas Ebner, Fabian Müller
BACKGROUND: In a recently described probe drug cocktail for clinically relevant drug transporters containing digoxin, furosemide, metformin and rosuvastatin, mutual interactions were essentially absent except for increases in the systemic exposure of rosuvastatin. To optimize the cocktail, we further examined the dose dependence of the effects of metformin and furosemide on rosuvastatin pharmacokinetics. METHODS: This was a randomized, open label, single center, six-treatment, six-period, six-sequence crossover trial...
July 6, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28683704/pharmacokinetic-monitoring-of-chronic-treatment-with-digoxin-from-primary-health-care
#12
Emma M García-Iranzo, Francisco J Rodríguez-Lucena, Carmen Matoses-Chirivella, Ana García-Monsalve, Ana Cristina Murcia-López, Andrés Navarro-Ruiz
INTRODUCTION: The serum digoxin concentration (SDC) should be between 0.8 and 2 ng/ml. The objective is to assess the pharmacokinetic monitoring of SDC performed from primary healthcare (PH) in patients with chronic treatment. METHODS: Cross-sectional retrospective study of patients with chronic treatment with digoxin belonging to the department of a General University Hospital.Data were analized: age, sex, diagnosis, number of serum digoxin concentration determinations, date and origin of the request for monitoring, analytical result and pharmacokinetic assessment are collected...
July 1, 2017: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/28682565/-digoxin-poisoning-new-prospects-for-therapy
#13
Alfonsina Marino, Lorenzo Giordano, Francesco Ardu
The filter has been approved by the Food and Drug Administration for the removal of beta-2 microglobulin in patient undergoing hemodialysis. We used the filter (the patient agrees) off label, in the course of digitalis intoxication and we have shown that the filter is capable of removing the drug effectively.
April 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28666993/digoxin-use-and-subsequent-clinical-outcomes-in-patients-with-atrial-fibrillation-with-or-without-heart-failure-in-the-engage-af-timi-48-trial
#14
Alon Eisen, Christian T Ruff, Eugene Braunwald, Rose A Hamershock, Basil S Lewis, Christian Hassager, Tze-Fan Chao, Jean Yves Le Heuzey, Michele Mercuri, Howard Rutman, Elliott M Antman, Robert P Giugliano
BACKGROUND: Digoxin is widely used in patients with atrial fibrillation despite the lack of randomized controlled trials. Observational studies report conflicting results regarding its association with mortality, perhaps because of residual confounding by the presence of heart failure (HF). METHODS AND RESULTS: In the ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trial, clinical outcomes of patients with atrial fibrillation with and without HF were examined by baseline digoxin use during a median follow-up of 2...
June 30, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28654904/digoxin-induced-anemia-among-patients-with-atrial-fibrillation-and-heart-failure-clinical-data-analysis-and-drug-gene-interaction-network
#15
Yubi Lin, Siqi He, Ruiling Feng, Zhe Xu, Wanqun Chen, Zifeng Huang, Yang Liu, Qianhuan Zhang, Bin Zhang, Kejian Wang, Shulin Wu
Digoxin is widely used to treat various heart conditions. In order to clarify the association between digoxin and anemia adverse reaction, we inspected case reports submitted to the FDA Adverse Event Reporting System (FAERS) between January 2004 and December 2015. These reports involved 75618 atrial fibrillation patients and 15699 heart failure patients. Compared to other therapies, digoxin treatment was significantly more likely to be concurrent with anemia adverse reaction among both atrial fibrillation patients (pooled OR = 1...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28652884/drug-absorption-related-nephrotoxicity-assessment-on-an-intestine-kidney-chip
#16
Zhongyu Li, Wentao Su, Yujuan Zhu, Tingting Tao, Dong Li, Xiaojun Peng, Jianhua Qin
Drug absorption in the intestine is tightly related to drug-induced nephrotoxicity, which is a relatively common side effect in clinical practice. It highlights a great need to develop predictive models with high accuracy in the early stage during new drug discovery and development. Herein, we presented a novel intestine-kidney chip, which recapitulated drug absorption in the intestine and its resultant drug toxicity on the kidney. This work aims to provide an integrated tool for accurate assessment of drug absorption-related nephrotoxicity in vitro...
May 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/28645513/atrial-fibrillation-current-therapies
#17
REVIEW
Romain Pariaut
A rate control or a rhythm control strategy can be applied to the management of atrial fibrillation. Rate control of atrial fibrillation consists of decreasing the ventricular response rate by limiting the number of supraventricular impulses that can travel through the atrioventricular node. The goal of decreasing heart rate in dogs with atrial fibrillation is usually achieved with a combination of the calcium channel blocker diltiazem and digoxin. Rhythm control of atrial fibrillation encompasses pharmacologic and nonpharmacologic methods to terminate the arrhythmia and restore sinus rhythm...
June 20, 2017: Veterinary Clinics of North America. Small Animal Practice
https://www.readbyqxmd.com/read/28644688/intraosseous-administration-of-antidotes-a-systematic-review
#18
Audrée Elliott, Pierre-André Dubé, Amélie Cossette-Côté, Laura Patakfalvi, Eric Villeneuve, Martin Morris, Sophie Gosselin
CONTEXT: Intraosseous (IO) access is an established route of administration in resuscitation situations. Patients with serious poisoning presenting to the emergency department may require urgent antidote therapy. However, intravenous (IV) access is not always readily available. OBJECTIVE: This study reviews the current evidence for IO administration of antidotes that could be used in poisoning. The primary outcome was mortality as a surrogate of efficacy. Secondary outcomes included hemodynamic variables, electrocardiographic variables, neurological status, pharmacokinetics outcomes, and adverse effects as defined by each article...
June 23, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28643402/clinical-findings-in-right-ventricular-noncompaction-in-hypoplastic-left-heart-syndrome
#19
Monique M Gardner, Meryl S Cohen
BACKGROUND: Noncompaction is a poorly understood form of cardiomyopathy that typically affects the left ventricle and may be associated with congenital heart disease. Right ventricular noncompaction (RVNC) may occur when the left ventricle is affected but is rarely seen in isolation. RVNC may have clinical significance affecting surgical and long-term outcomes. We describe the diagnosis and clinical course in three patients at our institution. METHODS: We performed a retrospective review of patients diagnosed with RVNC over a 12-month period at our institution and reviewed their imaging and clinical course...
June 23, 2017: Congenital Heart Disease
https://www.readbyqxmd.com/read/28633895/synthesis-of-meon-neoglycosides-of-digoxigenin-with-6-deoxy-and-2-6-dideoxy-d-glucose-derivatives-and-their-anticancer-activity
#20
Dong-Dong Wang, Xiao-San Li, Yu-Zhou Bao, Jie Liu, Xiao-Kun Zhang, Xin-Sheng Yao, Xue-Long Sun, Jin-Shan Tang
Cardiac glycosides show anticancer activities and their deoxy-sugar chains are vital for their anticancer effects. In order to study the structure-activity relationship (SAR) of cardiac glycosides toward cancers and get more potent anticancer agents, a series of MeON-neoglycosides of digoxigenin was synthesized and evaluated. First, ten 6-deoxy- and 2,6-dideoxy-d-glucopyranosyl donors were synthesized starting from methyl α-d-glucopyranoside and 2-deoxy-d-glucose. Meanwhile, the digoxigenin was obtained by acidic hydrolysis of commercially available digoxin as glycosyl acceptor...
August 1, 2017: Bioorganic & Medicinal Chemistry Letters
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