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21. Elimination of undifferentiated human embryonic stem cells by cardiac glycosides Full Text available with Trip Pro

-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). This phenomenon was not observed in human bone marrow mesenchymal stem cells (hBMMSCs). Most importantly, digoxin and lanatoside C did not affect the stem cells' differentiation ability. Consistently, the viability of the hESC-derived MSCs, neurons, and endothelium cells was not affected by the digoxin (...) and lanatoside C treatment. Furthermore, the in vivo experiments demonstrated that digoxin and lanatoside C prevented teratoma formation. To the best of our knowledge, this study is the first to describe the cytotoxicity and tumor prevention effects of cardiac glycosides in hESCs. Digoxin and lanatoside C are also the first FDA-approved drugs that demonstrated cytotoxicity in undifferentiated hESCs.

2017 Scientific reports

22. Efficacy and safety of digoxin in patients with heart failure and reduced ejection fraction according to diabetes status: An analysis of the Digitalis Investigation Group (DIG) trial. Full Text available with Trip Pro

Efficacy and safety of digoxin in patients with heart failure and reduced ejection fraction according to diabetes status: An analysis of the Digitalis Investigation Group (DIG) trial. Digoxin is recommended in symptomatic heart failure patients with reduced ejection fraction (HF-REF) in sinus rhythm and refractory to other evidence-based therapy. Although HF-REF patients with diabetes have worse functional status than those without, the effects of digoxin have not been specifically evaluated (...) according to diabetes status.We examined the efficacy and safety of digoxin in HF-REF patients with and without diabetes in the Digitalis Investigation Group trial. Mortality from all-cause, cardiovascular (CV) causes and heart failure (HF), along with HF hospitalisation and suspected digoxin toxicity were analyzed according to diabetes status and randomised treatment assignment.Of the 6800 patients, those with diabetes (n=1933) were older, more often women, had worse clinical status and more co

2016 International journal of cardiology Controlled trial quality: uncertain

23. Elderly patients with suspected chronic digoxin toxicity: A comparison of clinical characteristics of patients receiving and not receiving digoxin-Fab. (Abstract)

Elderly patients with suspected chronic digoxin toxicity: A comparison of clinical characteristics of patients receiving and not receiving digoxin-Fab. 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.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.There were 47 referrals. Digoxin-Fab was administered in 21 cases. It was given more commonly when the heart rate was <51/min or serum potassium was >5.0 mmol/L. Patients receiving digoxin-Fab were more likely to be on maintenance therapy

2018 Emergency medicine Australasia

24. PP087. Deep trial secondary analysis: Digoxin immune fab fragment treatment has additional benefits in endogenous digitalis-like factor positive preeclamptic women. (Abstract)

PP087. Deep trial secondary analysis: Digoxin immune fab fragment treatment has additional benefits in endogenous digitalis-like factor positive preeclamptic women. A double blinded placebo controlled clinical trial of a commercial digoxin immune Fab fragment (DIF) in preeclamptic (PE) women provided some benefit to treated subjects (1). In that study DIF, relative to placebo, prevented a decline in CrCl and lowered levels of endogenous digitalis-like factor (EDLF) activity as measured

2015 Pregnancy Hypertension Controlled trial quality: uncertain

25. Colored floaters as a manifestation of digoxin toxicity Full Text available with Trip Pro

Colored floaters as a manifestation of digoxin toxicity 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.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 (...) symptoms. On subsequent ophthalmic examination, the patient's visual acuity, field testing and color vision improved and he had normal Amsler grid test results.Colored floaters may occur in patients taking cardiac glycosides but this association has not been explored. Unlike optical illusions and visual hallucinations, floaters are entoptic phenomena casting a physical shadow upon the retina and their coloring likely arise from retinal dysfunction. Colored floaters may be a more common visual

2018 American journal of ophthalmology case reports

26. Prophylactic digoxin treatment reduces IL-17 production in vivo in the neonatal calf and moderates RSV-associated disease. Full Text available with Trip Pro

Prophylactic digoxin treatment reduces IL-17 production in vivo in the neonatal calf and moderates RSV-associated disease. Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality in human infants. Bovine RSV infection of neonatal calves is pathologically and immunologically similar to RSV infection in infants, and is therefore a useful preclinical model for testing novel therapeutics. Treatment of severe RSV bronchiolitis relies on supportive care and may include use (...) of bronchodilators and inhaled or systemic corticosteroids. Interleukin-17A (IL-17) is an inflammatory cytokine that plays an important role in neutrophil recruitment and activation. IL-17 is increased in children and rodents with severe RSV infection; and in calves with severe BRSV infection. It is currently unclear if IL-17 and Th17 immunity is beneficial or detrimental to the host during RSV infection. Digoxin was recently identified to selectively inhibit IL-17 production by antagonizing its transcription

2019 PLoS ONE

27. Digoxin and Mortality in Patients With Atrial Fibrillation Full Text available with Trip Pro

Digoxin and Mortality in Patients With Atrial Fibrillation Digoxin is widely used in patients with atrial fibrillation (AF).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.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. The authors investigated the independent association between serum digoxin concentration and mortality after multivariable adjustment.At baseline, 5,824 (32.5%) patients were receiving digoxin. Baseline digoxin use was not associated with an increased risk of death (adjusted hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 0.96 to 1.23; p = 0.19). However, patients with a serum digoxin concentration ≥1.2 ng/ml had a 56

2018 EvidenceUpdates

28. Changes in cardiac glycoside receptor sites, 86rubidium uptake and intracellular sodium concentrations in the erythrocytes of patients receiving digoxin during the early phases of treatment of cardiac failure in regular rhythm and of atrial fibrillation. Full Text available with Trip Pro

Changes in cardiac glycoside receptor sites, 86rubidium uptake and intracellular sodium concentrations in the erythrocytes of patients receiving digoxin during the early phases of treatment of cardiac failure in regular rhythm and of atrial fibrillation. 1 Measurements of the binding of 12-alpha-[3H]-digoxin to the membranes of intact erythrocytes, erythrocytic 86rubidium uptake and intraerythrocytic sodium concentrations have been made in the red cells of patients receiving digoxin (...) in the short-term for atrial fibrillation or cardiac failure in regular rhythm. 2 During the first few days of treatment [3H]-digoxin binding and 86rubidium uptake fall and intraerythrocytic sodium concentrations rise. 3 Subsequently parallel fluctuations occur in [3H]-digoxin binding and 86rubidium uptake but not in intraerythrocytic sodium concentrations and the significance of the fluctuations is discussed. 4 The values of all three measurements correlate significantly with the response of the heart

1979 British journal of clinical pharmacology

29. The uptake of cardiac glycosides by intestinal smooth muscle of the guinea-pig in relation to digitalis receptors Full Text available with Trip Pro

The uptake of cardiac glycosides by intestinal smooth muscle of the guinea-pig in relation to digitalis receptors 1. The accumulation and release of (3)H-digitoxin, (3)H-digoxin and (3)H-ouabain by isolated guinea-pig intestinal smooth muscle has been studied and compared with a pharmacological action due to inhibition of the sodium pump.2. The uptake of labelled cardiac glycosides can be described by means of an exponential function. The t of uptake was similar for the three compounds and did (...) not depend on the concentration.3. Analysis of the curve relating the uptake of cardiac glycosides at equilibrium to the bath concentration enabled a non-saturable and a saturable binding site to be distinguished.4. In contrast to the uptake observations, the onset of the pharmacological effect was dependent on the concentration, and furthermore the t((1/2)) for this effect was shorter.5. The release of cardiac glycosides proceeded more slowly than the uptake.6. The uptake of a labelled glycoside

1970 British journal of pharmacology

30. Role of endogenous digitalis-like factors in the clinical manifestations of severe preeclampsia: a sytematic review. (Abstract)

Role of endogenous digitalis-like factors in the clinical manifestations of severe preeclampsia: a sytematic review. Endogenous digitalis-like factor(s), originally proposed as a vasoconstrictor natriuretic hormone, was discovered in fetal and neonatal blood accidentally because it cross-reacts with antidigoxin antibodies (ADAs). Early studies using immunoassays with ADA identified the digoxin-like immuno-reactive factor(s) (EDLF) in maternal blood as well, and suggested it originated (...) in the feto-placental unit. Mammalian digoxin-like factors have recently been identified as at least two classes of steroid compounds, plant derived ouabain (O), and several toad derived bufodienolides, most prominent being marinobufagenin (MBG). A synthetic pathway for MBG has been identified in mammalian placental tissue. Elevated maternal and fetal EDLF, O and MBG have been demonstrated in preeclampsia (PE), and inhibition of red cell membrane sodium, potassium ATPase (Na, K ATPase (NKA)) by EDLF

2018 Clinical science (London, England : 1979)

31. Effect of digitalis level on readmission and mortality rate among heart failure reduced ejection fraction patients. Full Text available with Trip Pro

Effect of digitalis level on readmission and mortality rate among heart failure reduced ejection fraction patients. Digitalis has been used for over 200 years to treat patients with heart failure, and evidence supports its use to improve clinical symptoms and quality of life, but not survival. The objective of this retrospective study was to evaluate the effects of digitalis on readmission and mortality in patients with heart failure with reduced ejection fraction (HFrEF) who were receiving (...) current guideline recommended medical therapy.We reviewed medical record data from a retrospective cohort study of 1047 patients admitted to the hospital from 2005 to 2014 with decompensated HFrEF. 244 received digitalis, at some point during patient trajectory, and 803 never received digitalis. The primary outcomes of interest were the length of stay in hospital, readmission rates after discharge at 1, 6, 12, and 24 months and the overall mortality rate, at the same time points.We studied the effects

2018 Heart & Lung

32. Bacteria colonising Penstemon digitalis show volatile and tissue-specific responses to a natural concentration range of the floral volatile linalool Full Text available with Trip Pro

Bacteria colonising Penstemon digitalis show volatile and tissue-specific responses to a natural concentration range of the floral volatile linalool Bacteria on floral tissue can have negative effects by consuming resources and affecting nectar quality, which subsequently could reduce pollinator visitation and plant fitness. Plants however can employ chemical defences to reduce bacteria density. In North American, bee-pollinated Penstemon digitalis, the nectar volatile S-(+)-linalool can (...) influence plant fitness, and terpenes such as linalool are known for their antimicrobial properties suggesting that it may also play a role in plant-microbe interactions. Therefore, we hypothesized linalool could affect bacterial growth on P. digitalis plants/flowers. Because P. digitalis emits linalool from nectar and nectary tissue but not petals, we hypothesised that the effects of linalool could depend on tissue of origin due to varying exposure. We isolated bacteria from nectary tissue, petals

2018 Chemoecology

33. Oleandrin: A cardiac glycosides with potent cytotoxicity Full Text available with Trip Pro

Oleandrin: A cardiac glycosides with potent cytotoxicity Cardiac glycosides are used in the treatment of congestive heart failure and arrhythmia. Current trend shows use of some cardiac glycosides in the treatment of proliferative diseases, which includes cancer. Nerium oleander L. is an important Chinese folk medicine having well proven cardio protective and cytotoxic effect. Oleandrin (a toxic cardiac glycoside of N. oleander L.) inhibits the activity of nuclear factor kappa-light-chain

2013 Pharmacognosy reviews

34. [Plasma levels of cardiac glycosides and the electrocardiogram during moderately rapid and slow digitalization with beta-methyl-digoxin in normal volunteers (author's transl)]. (Abstract)

[Plasma levels of cardiac glycosides and the electrocardiogram during moderately rapid and slow digitalization with beta-methyl-digoxin in normal volunteers (author's transl)]. 4822437 1974 06 12 2015 11 19 0012-0472 99 8 1974 Feb Deutsche medizinische Wochenschrift (1946) Dtsch. Med. Wochenschr. [Plasma levels of cardiac glycosides and the electrocardiogram during moderately rapid and slow digitalization with beta-methyl-digoxin in normal volunteers (author's transl)]. 329-32 Belz G G GG (...) Rudofsky G G Belz G G ger Clinical Trial Comparative Study Journal Article Randomized Controlled Trial Glykosid-Plasmaspiegel und Elektrokardiogramm während mittelschneller und langsamer Sättigung mit beta-Methyldigoxin bei gesunden Probanden. Germany Dtsch Med Wochenschr 0006723 0012-0472 73K4184T59 Digoxin MLT4718TJW Rubidium IM Administration, Oral Adult Digoxin administration & dosage adverse effects blood metabolism pharmacology Dose-Response Relationship, Drug Electrocardiography Erythrocytes

1974 Deutsche medizinische Wochenschrift (1946) Controlled trial quality: uncertain

35. The acute changes seen in cardiac glycoside receptor sites, 86rubidium uptake and intracellular sodium concentrations in the erythrocytes of patients during the early phases of digoxin therapy are not found during chronic therapy: pharmacological and ther Full Text available with Trip Pro

The acute changes seen in cardiac glycoside receptor sites, 86rubidium uptake and intracellular sodium concentrations in the erythrocytes of patients during the early phases of digoxin therapy are not found during chronic therapy: pharmacological and ther 1 Measurements of the binding of 12-alpha-[3H]-digoxin to the membranes of intact erythrocytes, erythrocyte 86rubidium uptake and intraerythrocytic sodium concentrations have been made in the red cells of various groups of patients--those who (...) have not received digoxin, those during the early phases of treatment, those during chronic (greater than 2 months) treatment, and those toxic. 2 The values of those measurements in the patients in the early phases of therapy and in the toxic patients differed significantly from those of the untreated patients. 3 However, the values in the chronically treated patients were not different from those of the untreated patients. 4 The results suggest that the biochemical pharmacological effects

1979 British journal of clinical pharmacology

36. Recent changes in biological availability of digoxin. Effect of an alteration in 'Lanoxin' tablets. Full Text available with Trip Pro

Recent changes in biological availability of digoxin. Effect of an alteration in 'Lanoxin' tablets. 4818143 1974 05 28 2018 11 13 0007-0769 36 1 1974 Jan British heart journal Br Heart J Recent changes in biological availability of digoxin. Effect of an alteration in 'Lanoxin' tablets. 85-9 Shaw T R TR Howard M R MR Hamer J J eng Journal Article England Br Heart J 0370634 0007-0769 73K4184T59 Digoxin 8W8T17847W Urea AIM IM Biopharmaceutics Body Weight Digoxin administration & dosage blood

1974 British Heart Journal

37. Biological availability of digoxin from Lanoxin produced in the United Kingdom. Full Text available with Trip Pro

Biological availability of digoxin from Lanoxin produced in the United Kingdom. Though established quality control standards were maintained, the bioavailability of digoxin from Lanoxin tablets produced in the United Kingdom fell in 1969, and was restored in 1972. After 1.5 mg doses of representative batches, tablets made between 1969 and 1972 produced mean values for area under the 50 hours plasma concentration/time curve of 36.6 ng/ml/hr and four-day urinary excretion of 340 mug, compared (...) with respective values of 67.5 ng/ml/hr and 696 mug for recently produced tablets.After 0.5 mg doses of four recent independently produced batches of Lanoxin tablets no significant between-batch difference was found for area under the plasma concentration/time curve or cumulative urinary excretion.Absorption of digoxin from batches of Lanoxin manufactured since May 1972 is uniform and consistent. Content uniformity is an inadequate measure of tablet quality, and consistent digoxin bioavailability cannot

1973 British medical journal Controlled trial quality: uncertain

38. Digoxin Discontinuation and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction. (Abstract)

Digoxin Discontinuation and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction. The deleterious effects of discontinuation of digoxin on outcomes in ambulatory patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) receiving angiotensin-converting enzyme inhibitors are well-documented.The authors sought to determine the relationship between digoxin discontinuation and outcomes in hospitalized patients with HFrEF receiving more contemporary guideline (...) -directed medical therapies including beta-blockers and mineralocorticoid receptor antagonists.Of the 11,900 hospitalized patients with HFrEF (EF ≤45%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 3,499 received pre-admission digoxin, which was discontinued in 721 patients. Using propensity scores for digoxin discontinuation, estimated for each of the 3,499 patients, a matched cohort of 698 pairs of patients

2019 Journal of the American College of Cardiology

39. Influence of OATP1B1 and OATP1B3 mutations and glomerular filtration rate on trough serum digoxin concentration in the Chinese population: A prospective cohort study. Full Text available with Trip Pro

Influence of OATP1B1 and OATP1B3 mutations and glomerular filtration rate on trough serum digoxin concentration in the Chinese population: A prospective cohort study. Polymorphisms of organic anion transporting polypeptides (OATPs) have been reported to affect trough serum digoxin concentration (SDC). However, the association of these polymorphisms with trough SDC in Chinese heart failure patients has not been studied. We aim to explore whether OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G (...) >A influence trough SDC in Chinese heart failure patients and to make clinical recommendations.Chinese patients (n = 104) diagnosed with heart failure under long-term digoxin therapy (0.125 mg daily) were enrolled in this study. Blood samples were collected for the analysis of trough SDC (immunofluorescence) and the polymorphisms of OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G>A (PCR-RFLP and Sanger sequencing).Patients with glomerular filtration rate (GFR) under 30 mL/min had significantly higher

2019 Medicine

40. Digoxin Use and Associated Adverse Events Among Older Adults. (Abstract)

Digoxin Use and Associated Adverse Events Among Older Adults. Over the past 2 decades, guidelines for digoxin use have changed significantly. However, little is known about the national-level trends of digoxin use, hospitalizations for toxicity, and subsequent outcomes over this time period.To describe digoxin prescription trends, we conducted a population-level, cohort study using data from IQVIA, Inc.'s National Prescription Audit (2007-2014) for patients aged ≥65 years. Further (...) , in a national cohort of Medicare fee-for-service beneficiaries aged ≥65 years in the United States, we assessed temporal trends of hospitalizations associated with digoxin toxicity and the outcomes of these hospitalizations between 1999 and 2013.From 2007 through 2014, the number of digoxin prescriptions dispensed decreased by 46.4%; from 8,099,856 to 4,343,735. From 1999 through 2013, the rate of hospitalizations with a principal or secondary diagnosis of digoxin toxicity decreased from 15 to 2 per 100,000

2019 American Journal of Medicine

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