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Fred Chasalow, Lori Pierce-Cohen
We describe a novel steroid, which we have named "Ionotropin." Its unique features are: [1] it has 23 carbon atoms and [2] it is a phosphocholine ester. There are no other known mammalian steroids with either structural feature. Ionotropin cross reacts with digoxin-specific antibodies and may be the long-sought, endogenous, mammalian digoxin-like material (DLM). Using LC-MS, we identified three other phosphocholine steroids in serum. Two of these steroids also cross-react with digoxin specific antibodies...
March 14, 2018: Steroids
Sule Ozbilgin, Derya Aslan Yurtlu, Beyza Küçükoztaş, Gonca Kamacı, Sezen Korkut, Bülent Serhan Yurtlu, M Ensari Güneli, Volkan Hancı, Ali Günerli
Previous studies have shown that cyclodextrin group medicines bind to various drugs. The hypothesis of our study is to determine whether sugammadex could bind to digoxin and delay the cardiovascular toxicity of that drug. Twenty-eight sedated Wistar rats were infused with digoxin at 3 mg/h (0.25 mg/ml). Five minutes after the start of infusion, animals were treated with a bolus of either 16 mg/kg (Sgdx16), 100 mg/kg (Sgdx100), or 1000 mg/kg (Sgdx1000) sugammadex. The control group infusion did not contain sugammadex...
March 16, 2018: Cardiovascular Toxicology
Marie Madsen, Peter Riis Hansen, Lars Bo Nielsen, Renata Martins Cardoso, Miranda van Eck, Tanja Xenia Pedersen
Psoriasis is a chronic inflammatory skin disorder associated with several comorbidities including atherosclerosis. Disease mechanisms that may affect both psoriasis and atherosclerosis include activation of T helper 1 and T helper 17 cells. Imiquimod application is an established mouse model of psoriasis-like skin inflammation. The cardiac glycoside digoxin inhibits the master transcription factor of T helper 17 differentiation, retinoid acid receptor-related orphan nuclear receptor γt, and attenuates interleukin-17-dependent pathologies in mice...
March 12, 2018: American Journal of Pathology
Burak Ozgür, Lasse Saaby, Kristine Langthaler, Birger Brodin
The presented data are related to the research article entitled "Characterization of the IPEC-J2 MDR1 (iP-gp) cell line as a tool for identification of P-gp substrates" by Ozgur et al. (2017) [1]. This data report describes the challenges of investigating the concentration-dependent transport of P-glycoprotein (P-gp) substrates with relatively low aqueous solubility. Thus, we provide solubility data on two prototypical P-gp substrates, digoxin and rhodamine 123, representing P-gp substrates with a relatively low- and high-aqueous solubility, respectively...
February 2018: Data in Brief
Eli Muchtar, Morie A Gertz, Shaji K Kumar, Grace Lin, Barry Boilson, Alfredo Clavell, Martha Q Lacy, Francis K Buadi, Suzanne R Hayman, Prashant Kapoor, David Dingli, S Vincent Rajkumar, Angela Dispenzieri, Martha Grogan
AIM: Digoxin is considered contraindicated in light-chain (AL) amyloidosis, given reports of increased toxicity published 30-50 years ago. We sought to determine the frequency of digoxin toxicity in patients with AL. METHODS: We identified 107 patients with AL amyloidosis who received digoxin between 2000 and 2015. RESULTS: The median age was 65 and the median digoxin dose and estimated glomerular filtration rate were 0.125 mg/d and 55 ml/min/1...
March 12, 2018: Amyloid: the International Journal of Experimental and Clinical Investigation
Eric Shulman, Jay J Chudow, Tina Shah, Krina Shah, Ariel Peleg, Dmitriy Nevelev, Faraj Kargoli, Lynn Zaremski, Cecilia Berardi, Andrea Natale, Jorge Romero, Luigi Di Biase, John Fisher, Andrew Krumerman, Kevin J Ferrick
No previous studies have examined the interaction between body mass index (BMI) and race/ethnicity with the risk of atrial fibrillation (AF). We retrospectively followed 48,323 persons free of AF (43% Hispanic, 37% black, and 20% white; median age 60 years) for subsequent incident AF (ascertained from electrocardiograms). BMI categories included very severely underweight (BMI <15 kg/m2 ), severely underweight (BMI 15.1 to 15.9 kg/m2 ), underweight (BMI 16 to 18.4 kg/m2 ), normal (BMI 18.5 to 24.9 kg/m2 ), overweight (BMI 25...
February 12, 2018: American Journal of Cardiology
Xin-Jun Du, Yu-Xuan Zang, Hai-Bin Liu, Ping Li, Shuo Wang
Listeria monocytogenes is an important food-borne pathogenic bacterium that causes human disease, resulting in economic losses worldwide. The current detection methods for L. monocytogenes are not well suited for direct field testing because they involve complicated, time-consuming operations. A simple, efficient method is vital for L. monocytogenes detection. In this study, we combined isothermal recombinase polymerase amplification (RPA) with a lateral flow (LF) strip to rapidly and reliably detect L. monocytogenes...
March 10, 2018: Journal of Food Science
Mintu P Turakhia
No abstract text is available yet for this article.
March 13, 2018: Journal of the American College of Cardiology
Renato D Lopes, Roberto Rordorf, Gaetano M De Ferrari, Sergio Leonardi, Laine Thomas, Daniel M Wojdyla, Peter Ridefelt, John H Lawrence, Raffaele De Caterina, Dragos Vinereanu, Michael Hanna, Greg Flaker, Sana M Al-Khatib, Stefan H Hohnloser, John H Alexander, Christopher B Granger, Lars Wallentin
BACKGROUND: Digoxin is widely used in patients with atrial fibrillation (AF). OBJECTIVES: The goal of this paper was to explore whether digoxin use was independently associated with increased mortality in patients with AF and if the association was modified by heart failure and/or serum digoxin concentration. METHODS: The association between digoxin use and mortality was assessed in 17,897 patients by using a propensity score-adjusted analysis and in new digoxin users during the trial versus propensity score-matched control participants...
March 13, 2018: Journal of the American College of Cardiology
Naqash J Sethi, Emil E Nielsen, Sanam Safi, Joshua Feinberg, Christian Gluud, Janus C Jakobsen
BACKGROUND: During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless of concomitant heart failure. Our objective was to assess the benefits and harms of digoxin for atrial fibrillation and atrial flutter based on randomized clinical trials. METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, BIOSIS for eligible trials comparing digoxin versus placebo, no intervention, or other medical interventions in patients with atrial fibrillation or atrial flutter in October 2016...
2018: PloS One
Anne Pernille Ofstad, Dan Atar, Lars Gullestad, Gisle Langslet, Odd Erik Johansen
Diabetes and heart failure (HF) are both global epidemics with tremendous costs on society with increased rates of HF hospitalizations and worsened prognosis when co-existing, making it a significant "deadly duo." The evidence for pharmacological treatment of HF in patients with type 2 diabetes mellitus (T2DM) stems typically from either subgroup analyses of patients that were recruited to randomized controlled trials of HF interventions, usually in patients with reduced ejection fraction (EF), or from subgroup analyses of HF patients recruited to cardiovascular (CV) outcome trials (CVOT) of glucose lowering agents involving patients with T2DM...
March 8, 2018: Heart Failure Reviews
Michael V Kjelstrup, Line D F Nielsen, Malthe Hansen-Bruhn, Kurt V Gothelf
The most common method for quantifying small-molecule drugs in blood samples is by liquid chromatography in combination with mass spectrometry. Few immuno-based assays are available for the detection of small-molecule drugs in blood. Here we report on a homogeneous assay that enables detection of the concentration of digoxin spiked into in a plasma sample. The assay is based on a shift in the equilibrium of a DNA strand displacement competition reaction, and can be performed in 30 min for concentrations above 10 nM...
March 6, 2018: Biosensors
Alessandro Capucci, Laura Cipolletta, Federico Guerra, Irene Giannini
The main aim of current research on the field of atrial fibrillation (AF) treatment is to find new antiarrhythmic drugs with less side effects. Areas covered: Dronedarone and vernakalant showed promising result in term of efficacy and safety in selected patients. Ranolazine and colchicine are obtaining a role as a potential antiarrhythmic drug. Ivabradine is used in experimental studies for the rate control of AF. Moreover, new compounds (vanoxerine, moxonidine, budiodarone) are still under investigation. Monoclonal antibodies or selective antagonist of potassium channel are under investigation for long term maintenance of sinus rhythm...
March 6, 2018: Expert Opinion on Emerging Drugs
Deepa Prasad, Joni Steinberg, Christopher Snyder
Introduction Newborn atrial flutter can be treated by medications, pacing, or direct current cardioversion. The purpose is to compare the cost-effectiveness of digoxin, pacing, and direct current cardioversion for the treatment of atrial flutter in neonates. Materials and methods A decision tree model was developed comparing the efficacy and cost of digoxin, pacing, and direct current cardioversion based on a meta-analysis of published studies of success rates of cardioversion of neonatal atrial flutter (age<2 months)...
March 6, 2018: Cardiology in the Young
Morgan E Gibbs, Laura A Wilt, Kaitlyn V Ledwitch, Arthur G Roberts
P-glycoprotein (Pgp) is a multidrug resistance transporter that limits the penetration of a wide range of neurotherapeutics into the brain including opioids. The diphenylpropylamine opioids methadone and loperamide are structurally similar, but loperamide has about a 4-fold higher Pgp-mediated transport rate. In addition to these differences, they showed significant differences in their effects on Pgp-mediated ATP hydrolysis. The activation of Pgp-mediated ATP hydrolysis by methadone was monophasic, while loperamide activation of ATP hydrolysis was biphasic implying methadone has a single binding site and loperamide has two binding sites on Pgp...
February 27, 2018: Journal of Pharmaceutical Sciences
Zhuo Yu, Hai Feng, Xuehua Sun, Yunhui Zhuo, Man Li, Zhenhua Zhou, Lingying Huang, Yun Jiang, Xiaojun Zhu, Xin Zhang, Fan Le, Chao Zheng, Alfred Szelok Cheng, Yueqiu Gao
Hepatocellular carcinoma (HCC) is one of the most aggressive malignant tumors, of which treatment options are limited especially in advanced stage. Bufalin, the major digoxin-like component of the traditional Chinese medicine Chansu, exhibits significant antitumor activities in hepatoma cells, but the potential mechanism is obscure. Cell cycle-related kinase (CCRK) is recently identified to be a crucial oncogenic master regulator to drive hepatocarcinogenesis. Here we investigated the molecular function of bufalin on CCRK-regulated signaling pathway, and expounded the underlying mechanism in HCC suppression...
March 1, 2018: Scientific Reports
Azmil H Abdul-Rahim, Li Shen, Christopher J Rush, Pardeep S Jhund, Kennedy R Lees, John J V McMurray
AIMS: To evaluate the effects of digoxin in patients with the newly described phenotype of heart failure (HF) and mid-range ejection fraction (HFmrEF), attributed to mild left ventricular systolic dysfunction. METHODS AND RESULTS: We carried out a retrospective analysis of the Digitalis Investigation Group (DIG) trial which had 7788 patients available for analysis with a left ventricular ejection fraction (LVEF) ranging between 3% and 85%. We compared the effect of digoxin to placebo in three mutually exclusive groups of patients defined by LVEF category: <40% (HF with reduced LVEF, HFrEF, n = 5874), 40-49% (HFmrEF, n = 1195) and ≥50% (HF with preserved LVEF, HFpEF, n = 719)...
March 1, 2018: European Journal of Heart Failure
Elena V Bouzinova, Lise Hangaard, Christian Staehr, Aleksandra Mazur, Avelino Ferreira, Alexander Chibalin, Shaun L Sandow, Zijian Xie, Christian Aalkjaer, Vladimir V Matchkov
AIMS: The Na,K-ATPase is involved in a large number of regulatory activities including cSrc-dependent signalling. Upon inhibition of the Na,K-ATPase with ouabain, cSrc activation is shown to occur in many cell types. This study tests the hypothesis that acute potentiation of agonist-induced contraction by ouabain is mediated through Na,K-ATPase-cSrc signalling-dependent sensitization of vascular smooth muscle cells to Ca2+ . METHODS: Agonist-induced rat mesenteric small artery contraction was examined in vitro under isometric conditions and in vivo in anaesthetized rats...
February 26, 2018: Acta Physiologica
Blair McNamara, Jennefer Russo, Sarina Chaiken, Janet Jacobson, Jennifer Kerns
OBJECTIVE: We sought to qualitatively understand patients' experiences with digoxin as a step before dilation and evacuation (D&E). STUDY DESIGN: We recruited English-speaking women from one abortion health center where digoxin is routinely used before D&E. We interviewed participants one to three weeks after the D&E about physical and emotional experiences with digoxin and understanding of its purpose. Using grounded theory, we analyzed transcripts iteratively, identifying themes from interviews; we stopped recruitment when we reached thematic saturation...
February 22, 2018: Contraception
Adam Oesterle, Benjamin Weber, Roderick Tung, Niteesh K Choudhry, Jagmeet P Singh, Gaurav A Upadhyay
BACKGROUND: Although post-operative atrial fibrillation is common after non-cardiac surgery, there is a paucity of data regarding prophylaxis. We sought to determine if pharmacologic prophylaxis reduces the incidence of post-operative atrial fibrillation after non-cardiac surgery. METHODS: We performed an electronic search of Ovid MEDLINE, the Cochrane central register of controlled trials database, and SCOPUS from inception to 9/7/2016 and included prospective randomized studies in which patients in sinus rhythm underwent non-cardiac surgery and examined the incidence of post-operative atrial fibrillation as well as secondary safety outcomes...
February 21, 2018: American Journal of Medicine
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