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https://www.readbyqxmd.com/read/29339801/cardiac-glycoside-aglycones-inhibit-hiv-1-gene-expression-by-a-mechanism-requiring-mek1-2-erk1-2-signaling
#1
Raymond W Wong, Clifford A Lingwood, Mario A Ostrowski, Tyler Cabral, Alan Cochrane
The capacity of HIV-1 to develop resistance to current drugs calls for innovative strategies to control this infection. We aimed at developing novel inhibitors of HIV-1 replication by targeting viral RNA processing-a stage dependent on conserved host processes. We previously reported that digoxin is a potent inhibitor of this stage. Herein, we identify 12 other cardiac glycoside/aglycones or cardiotonic steroids (CSs) that impede HIV growth in HIV-infected T cells from clinical patients at IC50s (1.1-1.3 nM) that are 2-26 times below concentrations used in patients with heart conditions...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329000/synthesis-of-c3-neoglycosides-of-digoxigenin-and-their-anticancer-activities
#2
Xiao-San Li, Yi-Chang Ren, Yu-Zhou Bao, Jie Liu, Xiao-Kun Zhang, You-Wei Zhang, Xue-Long Sun, Xin-Sheng Yao, Jin-Shan Tang
Cardiac glycosides exhibit significant anticancer effects and the glycosyl substitution at C3 position of digoxigenin is pivotal for their biological activity. In order to study the structure-activity relationship (SAR) of cardiac glycosides toward cancers and explore more potent anticancer agents, a series of C3-O-neoglycosides and C3-MeON-neoglycosides of digoxigenin were synthesized by the Koenigs-Knorr and neoglycosylation method, respectively. In addition, digoxigenin bisdigitoxoside and monodigitoxoside were prepared from digoxin by sodium periodate (NaIO4) oxidation and 6-aminocaproic acid hydrolysis...
January 2, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29317917/assessing-appropriateness-of-drug-therapy-in-older-persons-development-and-application-of-a-medication-assessment-tool-for-long-term-management-of-atrial-fibrillation
#3
Marise Gauci, Francesca Wirth, Liberato Camilleri, Lilian M Azzopardi, Anthony Serracino-Inglott
Background: Atrial fibrillation (AF) is highly prevalent in older persons and is associated with considerable morbidity and mortality. Assessing appropriateness of drug therapy in AF may be facilitated by application of medication assessment tools (MATs). Objective: To develop, psychometrically evaluate and apply an innovative MAT for the long-term management of AF with particular relevance to older persons. Methods: Key recommendations from clinical practice guidelines for the long-term management of AF were selected and review criteria defining appropriate drug therapy were constructed as a 'qualifying statement' followed by a 'standard'...
October 2017: Pharmacy Practice
https://www.readbyqxmd.com/read/29317410/derivation-of-a-system-independent-ki-for-pgp-mediated-digoxin-transport-from-system-dependent-ic50-data-by-accounting-for-the-contribution-of-additional-digoxin-transporters
#4
Aqsaa Chaudhry, Git Chung, Adam Lynn, Akshata Yalvigi, Colin Brown, Harma Ellens, Michael O'Connor, Caroline Lee, Joe Bentz
It has been previously demonstrated that IC50 values for inhibition of digoxin transport across confluent cell monolayers are system-dependent. We have applied the structural mass action kinetics model for P-glycoprotein mediated transport of digoxin across confluent cell monolayers to fit IC50 curves for inhibition of digoxin transport. The model fit digoxin IC50 data from a subset of labs participating in the P-gp IC50 Initiative (2 Caco-2 labs, 1 LLC-PK1-hMDR1-NKI lab and 2 MDCKII-hMDR1-NKI labs), as well as IC50 data for inhibition of digoxin transport through monolayers of primary human proximal tubule cells (HPTC) using eight of the same inhibitors...
January 9, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29316267/elderly-patients-with-suspected-chronic-digoxin-toxicity-a-comparison-of-clinical-characteristics-of-patients-receiving-and-not-receiving-digoxin-fab
#5
Hooman Arbabian, Hwee Min Lee, Andis Graudins
OBJECTIVE: The aim of the present study was to compare clinical features of patients with elevated serum digoxin concentrations who were treated with digoxin-Fab with those where the immunotherapy was not given by a tertiary hospital toxicology service. METHODS: This was a retrospective series of patients with supratherapeutic serum digoxin concentrations referred to the toxicology service from August 2013 to October 2015. Data collected included demographics, presenting complaint, digoxin dose, other medications taken, serum digoxin, potassium and creatinine concentration on presentation and initial and post-digoxin-Fab heart rate...
January 8, 2018: Emergency Medicine Australasia: EMA
https://www.readbyqxmd.com/read/29315692/comprehensive-review-of-cardiovascular-toxicity-of-drugs-and-related-agents
#6
REVIEW
Přemysl Mladěnka, Lenka Applová, Jiří Patočka, Vera Marisa Costa, Fernando Remiao, Jana Pourová, Aleš Mladěnka, Jana Karlíčková, Luděk Jahodář, Marie Vopršalová, Kurt J Varner, Martin Štěrba
Cardiovascular diseases are a leading cause of morbidity and mortality in most developed countries of the world. Pharmaceuticals, illicit drugs, and toxins can significantly contribute to the overall cardiovascular burden and thus deserve attention. The present article is a systematic overview of drugs that may induce distinct cardiovascular toxicity. The compounds are classified into agents that have significant effects on the heart, blood vessels, or both. The mechanism(s) of toxic action are discussed and treatment modalities are briefly mentioned in relevant cases...
January 5, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29300488/atp-binding-cassette-transporter-a-subfamily-8-is-a-sinusoidal-efflux-transporter-for-cholesterol-and-taurocholate-in-mouse-and-human-liver
#7
Kazunari Sasaki, Masanori Tachikawa, Yasuo Uchida, Satoshi Hirano, Fumito Kadowaki, Michitoshi Watanabe, Sumio Ohtsuki, Tetsuya Terasaki
The ATP-binding cassette (ABC) transporter A subfamily 8 (ABCA8) belongs to the ABCA6-like transporters subgroup, which is distinct from the ABCA1-like subgroup in the ABCA family. The expression and function of the short-size human ABCA8 lacking one of the two ATP-binding domains for ATP hydrolysis, which are regularly present in the other ABCA transporters, have been reported. However, the functional differences between the short-size human ABCA8 and full-size human ABCA8 which has the two ATP-binding domains, remain unknown...
January 4, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29285820/maldi-imaging-detects-endogenous-digoxin-in-glioblastoma-cells-infected-by-zika-virus-would-it-be-the-oncolytic-key
#8
Estela de O Lima, Tatiane M Guerreiro, Carlos Fernando O R Melo, Diogo N de Oliveira, Daisy Machado, Marcelo Lancelloti, Rodrigo R Catharino
Recently, microcephaly cases have increased in Americas and have been matter of concern due to Zika virus (ZIKV) recent outbreak. Previous studies have shown that ZIKV-infected progenitor neuronal cells present morphological abnormalities and increased rates of cell death, which may be indicators of microcephaly causes. As recent studies indicate Zika virus' tropism for brain cells, how would a glioblastoma (GBM) lineage behave under ZIKV infection, considering GBM the most common and malignant brain tumor in adults, presenting extreme chemoresistance and high morbidity and mortality rates? The current trend of using genetically engineered oncolytic pathogens as a safe way to eliminate tumors is under development, with trials already in course...
December 28, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/29284111/digoxin-benefit-varies-by-risk-of-heart-failure-hospitalization-applying-the-tufts-mc-hf-risk-model
#9
Jenica N Upshaw, David van Klaveren, Marvin A Konstam, David M Kent
BACKGROUND: Digoxin has been shown to reduce heart failure hospitalizations with a neutral effect on mortality. It is unknown whether there is heterogeneity of treatment effect for digitalis therapy according to predicted risk of heart failure hospitalization. METHODS AND RESULTS: We conducted a post hoc analysis of the Digitalis Investigator Group (DIG) studies, randomized controlled trials of digoxin versus placebo in participants with heart failure and left ventricular ejection fraction less than or equal to 45% (main DIG study, n=6800) or >45% (ancillary DIG study, n=988)...
December 25, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/29274283/mechanistic-and-structural-insight-into-promiscuity-based-metabolism-of-cardiac-drug-digoxin-by-gut-microbial-enzyme
#10
Kundan Kumar, Shubham K Jaiswal, Gaurao V Dhoke, Gopal N Srivastava, Ashok K Sharma, Vineet K Sharma
The recent advances in microbiome studies have revealed the role of gut microbiota in altering the pharmacological properties of oral drugs, which contributes to patient-response variation and undesired effect of the drug molecule. These studies are essential to guide us for achieving the desired efficacy and pharmacological activity of the existing drug molecule or for discovering novel and more effective therapeutics. However, one of the main limitations is the lack of atomistic details on the binding and metabolism of these drug molecules by gut-microbial enzymes...
December 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29273768/small-molecule-tfeb-pathway-agonists-that-ameliorate-metabolic-syndrome-in-mice-and-extend-c-elegans-lifespan
#11
Chensu Wang, Hanspeter Niederstrasser, Peter M Douglas, Rueyling Lin, Juan Jaramillo, Yang Li, Nathaniel W Olswald, Anwu Zhou, Elizabeth A McMillan, Saurabh Mendiratta, Zhaohui Wang, Tian Zhao, Zhiqaing Lin, Min Luo, Gang Huang, Rolf A Brekken, Bruce A Posner, John B MacMillan, Jinming Gao, Michael A White
Drugs that mirror the cellular effects of starvation mimics are considered promising therapeutics for common metabolic disorders, such as obesity, liver steatosis, and for ageing. Starvation, or caloric restriction, is known to activate the transcription factor EB (TFEB), a master regulator of lipid metabolism and lysosomal biogenesis and function. Here, we report a nanotechnology-enabled high-throughput screen to identify small-molecule agonists of TFEB and discover three novel compounds that promote autophagolysosomal activity...
December 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29246961/first-line-antiarrhythmic-transplacental-treatment-for-fetal-tachyarrhythmia-a-systematic-review-and-meta-analysis
#12
REVIEW
Tarek Alsaied, Shankar Baskar, Munes Fares, Fares Alahdab, Richard J Czosek, Mohammad Hassan Murad, Larry J Prokop, Allison A Divanovic
BACKGROUND: There is no consensus on the most effective and best tolerated first-line antiarrhythmic treatment for fetal tachyarrhythmia. The purpose of this systematic review and meta-analysis was to compare the efficacy, safety, and fetal-maternal tolerance of first-line monotherapies for fetal supraventricular tachycardia and atrial flutter. METHODS AND RESULTS: A comprehensive search of several databases was conducted through January 2017. Only studies that made a direct comparison between first-line treatments of fetal tachyarrhythmia were included...
December 15, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29242064/hypoxia-inducible-factor-1-in-clinical-and-experimental-aortic-aneurysm-disease
#13
Wei Wang, Baohui Xu, Haojun Xuan, Yingbin Ge, Yan Wang, Lixin Wang, Jianhua Huang, Weiguo Fu, Sara A Michie, Ronald L Dalman
OBJECTIVE: Mural angiogenesis and macrophage accumulation are two pathologic hallmarks of abdominal aortic aneurysm (AAA) disease. The heterodimeric transcription factor hypoxia-inducible factor 1 (HIF-1) is an essential regulator of angiogenesis and macrophage function. In this study, we investigated HIF-1 expression and activity in clinical and experimental AAA disease. METHODS: Human aortic samples were obtained from 24 AAA patients and six organ donors during open abdominal surgery...
December 11, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/29220885/indexes-of-the-erythropoietin-level-in-the-blood-plasma-of-chronic-heart-failure-patients-with-anemia
#14
Kamala Kh Zahidova
BACKGROUND: Anemia aggravates the disease course and the survival rate of chronic heart failure (CHF) patients. The purpose of the study was to investigate the level of erythropoietin (EPO) in CHF patients with anemic syndrome, with the aim to more accurately assess the severity of the disease and its treatment, depending on the anemia degree. METHODS: Patients with ischemic CHF of I-IV functional class (FC) with and without anemia were examined (total number of patients=208, patients with anemia=174)...
December 7, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29218869/chemical-reaction-vector-embeddings-towards-predicting-drug-metabolism-in-the-human-gut-microbiome
#15
Emily K Mallory, Ambika Acharya, Stefano E Rensi, Peter J Turnbaugh, Roselie A Bright, Russ B Altman
Bacteria in the human gut have the ability to activate, inactivate, and reactivate drugs with both intended and unintended effects. For example, the drug digoxin is reduced to the inactive metabolite dihydrodigoxin by the gut Actinobacterium E. lenta, and patients colonized with high levels of drug metabolizing strains may have limited response to the drug. Understanding the complete space of drugs that are metabolized by the human gut microbiome is critical for predicting bacteria-drug relationships and their effects on individual patient response...
2018: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/29210311/the-role-of-gut-microbiota-in-the-modulation-of-drug-action-a-focus-on-some-clinically-significant-issues
#16
Diego Currò
A healthy gut microbiota is necessary for the normal operation of several body functions, including gastrointestinal sensitivity and motility, lipid and glucid metabolism, immune surveillance, and host behavior. In addition, intestinal bacteria contribute to determining the pharmacological properties of several drugs by producing different drug metabolizing enzymes. Areas covered: Four enzymatic processes are discussed: prodrug activation; drug inactivation; drug deconjugation; and hydrolysis of natural glycosides with further metabolism of released aglycones...
December 6, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29208503/maternal-complications-induced-by-digoxin-treatment-of-fetal-tachycardia-a-retrospective-series-of-18-cases
#17
S Moatassim, S Touleimat, T Hazelzet, M-D Brasseur, A Diguet, I Durand, E Verspyck
OBJECTIVE: To evaluate maternal tolerance to digoxin, used alone or associated to other antiarrhythmic drugs in the management of fetal tachycardia. PATIENTS AND METHODS: This retrospective study was conducted at Rouen University Hospital between January 2009 and July 2016. All women who have received a treatment by either digoxin alone or associated with another antiarrhythmic drug for fetal tachycardia were included in the study. Maternal cardiac and extracardiac adverse effects were reported and comparisons between electrocardiograms before and during treatment with digoxin alone were performed...
December 2, 2017: Journal of Gynecology Obstetrics and Human Reproduction
https://www.readbyqxmd.com/read/29202630/concurrent-new-drug-prescriptions-and-prognosis-of-early-breast-cancer-studies-using-the-danish-breast-cancer-group-clinical-database
#18
Deirdre Cronin-Fenton, Timothy L Lash, Thomas P Ahern, Per Damkier, Peer Christiansen, Bent Ejlertsen, Henrik T Sørensen
BACKGROUND: Myriad reports suggest that frequently used prescription drugs alter the viability of breast cancer cells in pre-clinical studies. Routine use of these drugs, therefore, may impact breast cancer prognosis, and could have important implications for public health. METHODS: The Danish Breast Cancer Group (DBCG) clinical database provides high-quality prospectively collected data on breast cancer diagnosis, treatment, and routine follow-up for breast cancer recurrence...
December 5, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29187799/appropriateness-of-digoxin-measurement-in-hospitalized-patients
#19
Seyma Oncu, Ayse Gelal, Ozgur Aslan, Reyhan S Ucku
Introduction: Measurement of serum digoxin concentrations before steady-state is reached results in a falsely low concentration, and may affect treatment safety. We evaluated the proportion of serum digoxin measurements performed before steady-state is reached and the reasons for inappropriate sampling in hospitalized patients. Materials and methods: Electronic medical records of patients hospitalized between January 2011 and December 2015 treated with oral digoxin, that had more than one digoxin measurement were included...
February 15, 2018: Biochemia Medica: časopis Hrvatskoga Društva Medicinskih Biokemičara
https://www.readbyqxmd.com/read/29174246/incidence-of-drug-induced-torsades-de-pointes-with-intravenous-amiodarone
#20
Jayaprakash Shenthar, Jayasheelan Mambally Rachaiah, Vivek Pillai, Siva Sankara Chakali, Vidhyakar Balasubramanian, Manjunath Chollenhalli Nanjappa
AIM: To define the incidence, presentation, and outcomes of drug-induced Torsades de Pointes (TdP) with intravenous (IV) amiodarone. METHODS: From January 2014 to August 2016 a total of 268 patients received IV amiodarone, 142 for ventricular tachycardia, 104 for atrial flutter/fibrillation, and 22 for incessant atrial tachycardia. A uniform dosing of amiodarone to yield 1gm/day was used in all patients. RESULTS: Four of the 268 patients (M:F 1:3) with mean age of 51...
November 2017: Indian Heart Journal
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