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https://www.readbyqxmd.com/read/29780940/colored-floaters-as-a-manifestation-of-digoxin-toxicity
#1
Lynn Shi, Linus D Sun, Jeffrey G Odel
Purpose: Since its report in one patient more than 70 years ago, digitalis-induced colored muscae volitantes have not surfaced again in the literature. We report here a case of digoxin induced colored floaters. Observations: An 89-year-old man on 0.25 mg digoxin daily developed visual hallucinations and colored floaters. He had floaters in the past but now they were in various colors including yellow, green, blue and red, though predominantly in yellow. These "weirdly" shaped little particles wiggled around as if in a viscous solution and casted shadows in his vision...
June 2018: American Journal of Ophthalmology Case Reports
https://www.readbyqxmd.com/read/29778924/cerbera-odollam-toxicity-a-review
#2
REVIEW
Ritesh G Menezes, Muhammad Shariq Usman, Syed Ather Hussain, Mohammed Madadin, Tariq Jamal Siddiqi, Huda Fatima, Pradhum Ram, Syed Bilal Pasha, S Senthilkumaran, Tooba Qadir Fatima, Sushil Allen Luis
Cerbera odollam is a plant species of the Apocynaceae family. It is often dubbed the 'suicide tree' due to its strong cardiotoxic effects, which make it a suitable means to attempt suicide. The plant grows in wet areas in South India, Madagascar, and Southeast Asia; and its common names include Pong-Pong and Othalanga. The poison rich part of the plant is the kernel which is present at the core of its fruit. The bioactive toxin in the plant is cerberin, which is a cardiac glycoside of the cardenolide class...
May 9, 2018: Journal of Forensic and Legal Medicine
https://www.readbyqxmd.com/read/29768713/clinical-drug-drug-interaction-potential-of-bfe1224-prodrug-of-antifungal-ravuconazole-using-two-types-of-cocktails-in-healthy-subjects
#3
Yasuyuki Ishii, Yuko Ito, Shunji Matsuki, Kasumi Sanpei, Osamu Ogawa, Kenji Takeda, Edgar L Schuck, Naoto Uemura
BFE1224, prodrug of ravuconazole, is a novel, once-daily, oral, triazole antifungal drug, and currently in development for the treatment of onychomycosis. The clinical drug-drug interaction (DDI) potential of BFE1224 with cytochrome P450 (CYP) and transporter was assessed by using two types of cocktails in healthy subjects in separate clinical studies. The CYP and transporter cocktails consisted of caffeine/tolbutamide/omeprazole/dextromethorphan/midazolam used in study 1 and digoxin/rosuvastatin used in study 2...
May 16, 2018: Clinical and Translational Science
https://www.readbyqxmd.com/read/29761785/discovery-and-characterization-of-a-prevalent-human-gut-bacterial-enzyme-sufficient-for-the-inactivation-of-a-family-of-plant-toxins
#4
Nitzan Koppel, Jordan E Bisanz, Maria-Eirini Pandelia, Peter J Turnbaugh, Emily P Balskus
Although the human gut microbiome plays a prominent role in xenobiotic transformation, most of the genes and enzymes responsible for this metabolism are unknown. Recently, we linked the two-gene 'cardiac glycoside reductase' ( cgr ) operon encoded by the gut Actinobacterium Eggerthella lenta to inactivation of the cardiac medication and plant natural product digoxin. Here, we compared the genomes of 25 E. lenta strains and close relatives, revealing an expanded 8-gene cgr -associated gene cluster present in all digoxin metabolizers and absent in non-metabolizers...
May 15, 2018: ELife
https://www.readbyqxmd.com/read/29754673/prevalent-digoxin-use-and-subsequent-risk-of-death-or-hospitalization-in-ambulatory-heart-failure-patients-with-a-reduced-ejection-fraction-findings-from-the-heart-failure-a-controlled-trial-investigating-outcomes-of-exercise-training-hf-action-randomized-controlled
#5
Andrew P Ambrosy, Ankeet S Bhatt, Amanda L Stebbins, Lisa M Wruck, Marat Fudim, Stephen J Greene, William E Kraus, Christopher M O'Connor, Ileana L Piña, David J Whellan, Robert J Mentz
BACKGROUND: Despite more than 200 years of clinical experience and a pivotal trial, recently published research has called into question the safety and efficacy of digoxin therapy in heart failure (HF). METHODS: HF-ACTION (ClinicalTrials.gov Number: NCT00047437) enrolled 2331 outpatients with HF and an EF ≤35% between April 2003 and February 2007 and randomized them to aerobic exercise training versus usual care. Patients were grouped according to prevalent digoxin status at baseline...
May 2018: American Heart Journal
https://www.readbyqxmd.com/read/29743548/combination-of-anti-vascular-agent-dmxaa-and-hif-1%C3%AE-inhibitor-digoxin-inhibits-the-growth-of-melanoma-tumors
#6
Ryszard Smolarczyk, Tomasz Cichoń, Ewelina Pilny, Magdalena Jarosz-Biej, Aleksandra Poczkaj, Natalia Kułach, Stanisław Szala
Vascular disrupting agents as DMXAA inhibit tumor growth only for a short period of time followed by rapid tumor regrowth. Among others, hypoxia and presence of transcription factor HIF-1α are responsible for tumors regrowth. The aim of our study was to investigate the inhibition of murine melanoma growth by combining two agents: anti-vascular - DMXAA and the HIF-1α inhibitor - digoxin and explaining the mechanism of action of this combination. After DMXAA treatment tumor size was reduced only for a limited time...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29741399/enzalutamide-and-analytical-interferences-in-digoxin-assays
#7
Marie Deguigne, Marion Brunet, Chadi Abbara, Alain Turcant, Gaël Le Roux, Bénédicte Lelièvre
OBJECTIVE: We report two cases of elevated digoxin plasma levels in patients receiving enzalutamide. Cases reported: The first patient, an 84-year-old male treated with enzalutamide, was hospitalized due to deterioration in his general state. Atrial fibrillation was discovered and treatment with digoxin was initiated. Supratherapeutic digoxin concentrations (4 µg/L and 3.5 µg/L 3 days later) led to treatment being stopped despite the lack of clinical or biological signs of overdose...
May 9, 2018: Clinical Toxicology
https://www.readbyqxmd.com/read/29738843/transporter-dependent-cytotoxicity-of-antiviral-drugs-in-primary-cultures-of-human-proximal-tubular-cells
#8
Lawrence H Lash, Caroline A Lee, Clynn Wilker, Vishal Shah
The role of plasma membrane transporters in the nephrotoxicity of two antiretroviral drugs, cidofovir and tenofovir, was studied in primary cultures of human proximal tubular (hPT) cells. Cells were grown on Transwell filter inserts to maintain epithelial polarity and access to either the apical or basolateral plasma membrane. The function of relevant membrane transporters, organic anion transporter 1 and 3 (OAT1/3), P-glycoprotein (multidrug resistance protein-1; P-gp or MDR1), and organic cation transporter 2 (OCT2), was validated by measurements of apical-to-basolateral and basolateral-to-apical fluxes of furosemide, digoxin, and metformin, respectively...
May 5, 2018: Toxicology
https://www.readbyqxmd.com/read/29724996/wwox-controls-hepatic-hif1%C3%AE-to-suppress-hepatocyte-proliferation-and-neoplasia
#9
Muhannad Abu-Remaileh, Abed Khalaileh, Eli Pikarsky, Rami I Aqeilan
Liver cancer is one of the most lethal malignancies with very poor prognosis once diagnosed. The most common form of liver cancer is hepatocellular carcinoma (HCC). The WW domain-containing oxidoreductase (WWOX) is a large gene that is often perturbed in a wide variety of tumors, including HCC. WWOX has been shown to act as a tumor suppressor modulating cellular metabolism via regulating hypoxia-inducible factor 1α (HIF-1α) levels and function. Given that WWOX is commonly inactivated in HCC, we set to determine whether specific targeted deletion of murine Wwox affects liver biology and HCC development...
May 3, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29721508/risk-factors-for-failure-of-direct-current-cardioversion-in-patients-with-type-2-diabetes-mellitus-and-atrial-fibrillation
#10
Handrean Soran, Moulinath Banerjee, Jamal B Mohamad, Safwaan Adam, Jan Hoong Ho, Shakawan M Ismaeel, Shaishav Dhage, Akheel A Syed, Ibrahem M A Abdulla, Naveed Younis, Rayaz A Malik
Introduction: Type 2 diabetes mellitus (T2DM) is a well-recognised risk factor for cardiovascular disease and the prevalence of atrial fibrillation (AF) is higher among patients with T2DM. Direct current cardioversion (DCCV) is an important management option in persistent AF. We sought to determine independent risk factors for immediate and short-term outcomes of DCCV for treatment of AF in patients with T2DM. Methods: Retrospective outcome analysis of DCCV for persistent AF in 102 T2DM patients compared with 102 controls...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29719229/digoxin-suppresses-pyruvate-kinase-m2-promoted-hif-1%C3%AE-transactivation-in-steatohepatitis
#11
Xinshou Ouyang, Sheng-Na Han, Ji-Yuan Zhang, Evangelos Dioletis, Balazs Tamas Nemeth, Pal Pacher, Dechun Feng, Ramon Bataller, Joaquin Cabezas, Peter Stärkel, Joan Caballeria, Rebecca LePine Pongratz, Shi-Ying Cai, Bernd Schnabl, Rafaz Hoque, Yonglin Chen, Wei-Hong Yang, Irma Garcia-Martinez, Fu-Sheng Wang, Bin Gao, Natalie Julia Torok, Richard Glenn Kibbey, Wajahat Zafar Mehal
No abstract text is available yet for this article.
May 1, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29709579/new-insights-in-the-in-vitro-characterisation-and-molecular-modelling-of-the-p-glycoprotein-inhibitory-promiscuity
#12
Giovanni Bocci, Amélie Moreau, Philippe Vayer, Claire Denizot, Olivier Fardel, Yannick Parmentier
The presence of several binding sites for both substrates and inhibitors is yet a poorly explored thematic concerning the assessment of the drug-drug interactions risk due to interactions of multiple drugs with the human transport protein P-glycoprotein (P-gp or MDR1, gene ABCB1). In this study we measured the inhibitory behaviour of a set of known drugs towards P-gp by using three different probe substrates (digoxin, Hoechst 33,342 and rhodamine 123). A structure-based model was built to unravel the different substrates binding sites and to rationalize the cases where drugs were not inhibiting all the substrates...
April 27, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29690635/quantitative-analysis-of-four-catechins-from-green-tea-extract-in-human-plasma-using-ultra-performance-liquid-chromatography-tandem-mass-spectrometry-for-pharmacokinetic-studies
#13
Jeong-Eun Park, Tae-Eun Kim, Kwang-Hee Shin
Green tea is consumed as a beverage worldwide and has beneficial effects, such as a lower risk of cardiovascular disease and cancer. A quantitative analysis of the beneficial components in plasma is important for understanding the potential health benefits of green tea. Four catechins—epigallocatechin-3-gallate (EGCG), epicatechin-3-gallate (ECG), epigallocatechin (EGC), and epicatechin (EC)—which account for the majority of the components of green tea, were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)...
April 23, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29678986/detecting-risk-of-postural-hypotension-drop-derivation-and-validation-of-a-prediction-score-for-primary-care
#14
Christopher Elles Clark, Daniel Thomas, Fiona C Warren, David J Llewellyn, Luigi Ferrucci, John L Campbell
OBJECTIVES: Falls are a common problem in older people. Postural hypotension contributes to falls but is often asymptomatic. In the absence of symptoms, postural hypotension is only infrequently checked for in clinical practice. We undertook this study to derive, validate and explore the prospective associations of a prediction tool to identify people likely to have unrecognised postural hypotension. DESIGN AND SETTING: Cross-sectional and prospective multivariable cohort analysis...
April 20, 2018: BMJ Open
https://www.readbyqxmd.com/read/29678842/biotin-at-high-concentration-interferes-with-the-loci-digoxin-assay-but-the-petinia-phenytoin-assay-is-not-affected
#15
Joe J Rodriguez, Fernando Acosta, Lavern Bourgeois, Amitava Dasgupta
Many automated immunoassays incorporate biotinylated antibodies and streptavidin-coated magnetic beads in the assay design. Biotin at elevated concentrations may interfere with these immunoassays. We evaluated potential interference of biotin on serum digoxin (LOCI assay utilizing biotinylated antibody) and phenytoin (PETINIA assay; no biotinylated antibody) measurements using the Vista 1500 analyzer. Aliquots of drug-free serum pool were supplemented with various biotin concentrations (range: 1 ng/mL to 250 ng/mL) followed by measuring apparent digoxin and phenytoin levels using appropriate immunoassays...
March 2018: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/29675974/value-of-digoxin-in-patients-with-heart-failure-new-pieces-to-the-puzzle
#16
EDITORIAL
Dirk J van Veldhuisen, Michiel Rienstra, Peter van der Meer
No abstract text is available yet for this article.
April 20, 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29675426/a-novel-method-for-drug-screen-to-regulate-g-protein-coupled-receptors-in-the-metabolic-network-of-alzheimer-s-disease
#17
Yang Li, Wei Zheng, Wuyun Qiqige, Shujuan Cao, Jishou Ruan, Yanping Zhang
Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder and the pathogenesis of AD is poorly understood. G protein-coupled receptors (GPCRs) are involved in numerous key AD pathways and play a key role in the pathology of AD. To fully understand the pathogenesis of AD and design novel drug therapeutics, analyzing the connection between AD and GPCRs is of great importance. In this paper, we firstly build and analyze the AD-related pathway by consulting the KEGG pathway of AD and a mass of literature and collect 25 AD-related GPCRs for drug discovery...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29665130/optimization-of-a-drug-transporter-probe-cocktail-potential-screening-tool-for-transporter-mediated-drug-drug-interactions
#18
Peter Stopfer, Thomas Giessmann, Kathrin Hohl, Sabine Hutzel, Sven Schmidt, Dietmar Gansser, Naoki Ishiguro, Mitchell E Taub, Ashish Sharma, Thomas Ebner, Fabian Müller
AIMS: Previous pharmacokinetic characterization of a transporter probe cocktail containing digoxin (P-gp), furosemide (OAT1, OAT3), metformin (OCT2, MATE1, MATE2-K) and rosuvastatin (OATP1B1, OATP1B3, BCRP) in healthy subjects showed increases in rosuvastatin systemic exposure compared to rosuvastatin alone. In this trial, the doses of metformin and furosemide as putative perpetrators were reduced to eliminate their drug-drug interaction (DDI) with rosuvastatin. METHODS: In a randomized, open label, single center, five-treatment, five-period crossover trial, 30 healthy male subjects received as reference treatments separately 0...
April 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29660142/use-of-digoxin-in-atrial-fibrillation-one-step-further-in-the-mortality-controversy-from-the-affirm-study
#19
Richard Charnigo, Paul Khairy, Jing Guo, Azadeh Shohoudi, Claude S Elayi
BACKGROUND: Whether there is a causal association between digoxin and mortality among patients with atrial fibrillation (AF), with or without congestive heart failure (HF), has been controversial; in particular, two prior analyses of data from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial have yielded conflicting results. We sought to investigate how digoxin impacts mortality, in the full AFFIRM cohort and for various subgroups, by applying marginal structural modeling (MSM) to AFFIRM data...
April 16, 2018: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/29653073/a-zebrafish-heart-failure-model-for-assessing-therapeutic-agents
#20
Xiao-Yu Zhu, Si-Qi Wu, Sheng-Ya Guo, Hua Yang, Bo Xia, Ping Li, Chun-Qi Li
Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection...
March 20, 2018: Zebrafish
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