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Immunoreactive digoxin-like activity was found in the Chinese medicine, KYUSHIN tablet, taken popularly in Japan without prescription. The antibodies used in the assays of digoxin reacted with Ch'an-su, the major effective component of KYUSHIN, which contained cardiotonic steroids with a chemical structure similar to that of digoxin. One tablet of KYUSHIN had digoxin-like immunoreactivity equivalent to 1.9 micrograms. (TDx analyzer), 1.5 micrograms (Du Pont aca analyzer) and 72 micrograms digoxin (Enzymun-Test, Boehringer). These different equivalencies may be attributed to differences in cross-reactivity of the antibody used in the immunoassays. Two healthy volunteers took two KYUSHIN tablets three times a day, a typical dose, and digoxin-like immunoreactivity reached almost 0.4 microgram/l in 0.5 day. Recently, a competitive digoxin chemiluminescent immunoassay has been developed by Ciba Corning ACS 180. The assay utilizes an acridinium-ester labelled mouse monoclonal digoxin antibody as the tracer. In the extracted solution of KYUSHIN and serum after administration of two tablets, the digoxin-like immunoreactivity value on the Ciba Corning ACS 180 digoxin assay was < 0.10 microgram/l (off-range low). Therapeutic drug monitoring should be interpreted carefully in patients taking Chinese medicines, many of which contain the Ch'an-su component.
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Chronic systemic hypertension causes cardiac pressure overload leading to increased myocardial O(2) consumption. Hypoxia-inducible factor 1 (HIF-1) is a master regulator of O(2) homeostasis. Mouse embryos lacking expression of the O(2)-regulated HIF-1α subunit die at midgestation with severe cardiac malformations and vascular regression. Here we report that Hif1a(f/f);Tie2-Cre conditional knockout mice, which lack HIF-1α expression only in Tie2(+) lineage cells, develop normally, but when subjected to pressure overload induced by transaortic constriction (TAC), they manifest rapid cardiac decompensation, which is accompanied by excess cardiac fibrosis and myocardial hypertrophy, decreased myocardial capillary density, increased myocardial hypoxia and apoptosis, and increased TGF-β signaling through both canonical and noncanonical pathways that activate SMAD2/3 and ERK1/2, respectively, within endothelial cells of cardiac blood vessels. TAC also induces dilatation of the proximal aorta through enhanced TGF-β signaling in Hif1a(f/f);Tie2-Cre mice. Inhibition of TGF-β signaling by treatment with neutralizing antibody or pharmacologic inhibition of MEK-ERK signaling prevented TAC-induced contractile dysfunction and pathological remodeling. Thus, HIF-1 plays a critical protective role in the adaptation of the heart and aorta to pressure overload by negatively regulating TGF-β signaling in endothelial cells. Treatment of wild-type mice with digoxin, which inhibits HIF-1α synthesis, resulted in rapid cardiac failure after TAC. Although digoxin has been used for decades as an inotropic agent to treat heart failure, it does not improve survival, suggesting that the countertherapeutic effects of digoxin observed in the TAC mouse model may have clinical relevance.
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The isoprenoid pathway produces three key metabolites--digoxin (membrane sodium-potassium ATPase inhibitor and regulator of neurotransmitter/aminoacid transport), dolichol (regulates N-glycosylation of proteins) and ubiquinone (free radical scavenger). This was assessed in patients with essential hypertension, familial hypotension, acute coronary artery disease and acute thrombotic strokes. The pathway was also assessed in patients with right hemispheric, left hemispheric and bihemispheric dominance for comparison. In patients with acute coronary artery disease, acute thrombotic stroke, essential hypertension and right hemispheric dominance, there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels and low ubiquinone and high free radical levels. There was also an increase in tryptophan catabolites, reduction in tyrosine catabolites, increase in cholesterol-phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in this group of patients as well as in those with right hemispheric dominance. In patients with familial hypotension and left hemispheric dominance, the patterns were reversed. The role of a dysfunctional isoprenoid pathway and endogenous digoxin in the pathogenesis of essential hypertension and familial hypotension and in thrombotic vascular disease in relation to hemispheric dominance is discussed.
In this study, we have developed a rapid and reliable LC-MS/MS method for the therapeutic monitoring of digoxin in human serum.
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Irish Wolfhound dogs were prospectively randomized to receive pimobendan (Vetmedin®), benazepril HCl (Fortekor®), or methyldigoxin (Lanitop®) monotherapy in a 1:1:1 ratio in a blinded clinical trial. The prospectively defined composite primary endpoint was onset of CHF or sudden death. To assure stringent evaluation of treatment effect, data from dogs complying with the study protocol were analyzed.
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With the increasing number of implantable cardioverter-defibrillator (ICD) implantations in patients with sustained ventricular tachyarrhythmias, there is a growing interest in typical complications associated with this therapy. We analyzed the reasons and the incidence of inadequate therapy deliveries in 100 patients with epicardial (n = 27) or transvenous (n = 73) ICDs during a follow-up period of 10 +/- 8 months. A total of 21 of 100 patients received inadequate therapies. The most common reason was sinus tachycardia in eleven patients. Additional unnecessary shocks were avoided by reprogramming and application of beta-blockers. Lead failures caused the erroneous detection and defibrillation of ventricular fibrillation without any preceding clinical symptoms in four patients with an epicardial and in one patient with a transvenous ICD. All patients underwent successful surgical revision of their system. Atrial fibrillation with rapid ventricular response triggered inadequate shocks in four patients. Following digoxin administration no patient had additional inadequate shocks. In one patient non-sustained tachycardias caused unnecessary defibrillations. These results demonstrate that inadequate defibrillations are a common complication in patients after ICD-placement. The performance of x-ray, stress testing, and Holter monitoring on a regular basis may facilitate early diagnosis of possible reasons for unnecessary therapy deliveries. The improvement of detection and memory functions in future ICD-generations appears to be mandatory as well.
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Retrospective case series using patient records of Equine University Clinic of Utrecht University and Rossdales Equine Hospital, Newmarket.
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Using four different digoxin kits, it was disclosed that the majority of various samples including amniotic fluid, cord blood, and serum from neonates contained substantial levels of digoxin-like immunoreactive substance. The differences in data seemed to be due to the range of epitopes which are recognized by antidigoxin antiserum. The day-to-day studies on sera serially obtained from infants at birth to 48 days old revealed that the level of the substance (0.31 +/- 0.12 ng/ml) in sera of the 1-day-old neonates rapidly declined to the level of 0.1 ng/ml by the 2nd postnatal wk and thereafter gradually declined. The immunological specificity and accuracy of the detection of digoxin-like immunoreactive substance was confirmed by a sample dilution test, a recovery test for standard digoxin, and an absorption test with antidigoxin antiserum. The amniotic fluid and cord blood also contained four to eight times more of a digitoxin-like immunoreactive substance than they did digoxin-like immunoreactive substance. A significant correlation was observed between the levels of digoxin-like immunoreactive substance and of digitoxin-like immunoreactive substance (p less than 0.01).
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Atrial fibrillation is a common, but potentially preventable, complication following coronary artery bypass graft (CABG) surgery.
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Since we have previously shown that the ratio of the 17.5-/22-kDa GH1 transcripts correlates with severity of the IGHD II phenotype, our findings here suggest that selected previously unconsidered agents could possibly reduce the severity of IGHD II, while other agents could possibly exacerbate the disease phenotype.
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A digoxin-like immunoreactive substance (DLIS) has been reported in the amniotic fluid. Since radioimmunoassay kits are standardized using serum-based standards, we hypothesized that measurement of DLIS may be an artifact related to the low protein content of amniotic fluid. We analyzed 12 amniotic fluid samples before and after supplementation with lyophilized human serum. The means +/- SDs for DLIS (nmol/l) at protein concentrations of 0, 32 and 63 g/l were 1.4 +/- 0.16, 0.6 +/- 0.09, and 0.4 +/- 0.09 nmol/l, respectively. We, therefore, hypothesize that DLIS in amniotic fluid may in part be explained by a technical artifact.
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Sensory neurons mediate diabetic peripheral neuropathy. Using a mouse model of diabetic peripheral neuropathy (BKS.Cg-m+/+Lepr(db)/J (db/db) mice) and cultured dorsal root ganglion (DRG) neurons, the present study showed that hyperglycemia downregulated miR-146a expression and elevated interleukin-1 receptor-activated kinase (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) levels in DRG neurons. In vitro, elevation of miR-146a by miR-146a mimics in DRG neurons increased neuronal survival under high-glucose conditions. Downregulation and elevation of miR-146a in DRG neurons, respectively, were inversely related to IRAK1 and TRAF6 levels. Treatment of diabetic peripheral neuropathy with sildenafil, a phosphodiesterase type 5 inhibitor, augmented miR-146a expression and decreased levels of IRAK1 and TRAF6 in the DRG neurons. In vitro, blockage of miR-146a in DRG neurons abolished the effect of sildenafil on DRG neuron protection and downregulation of IRAK1 and TRAF6 proteins under hyperglycemia. Our data provide the first evidence showing that miR-146a plays an important role in mediating DRG neuron apoptosis under hyperglycemic conditions.
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During the hospital stays, 192 ADRs were identified in 183 patients (5.8% of the sample). Cardiovascular and arrhythmic complications (20.3% of all ADRs) were the most frequent ADRs, followed by gastrointestinal (18.8%), dermatologic and allergic (12.5%), hemorrhagic (11.5%), and electrolyte (9.9%) disturbances. Adverse drug reactions were recorded in 101 (7.4%) of 1363 depressed patients and in 82 (4.6%) of 1771 nondepressed patients (P =.001). After adjusting for potential confounders, depression was associated with a significantly higher rate of ADRs (odds ratio, 1.58; 95% confidence interval, 1.14-2.20; P =.006). This effect seemed more pronounced in women (odds ratio, 1.85; 95% confidence interval, 1.16-2.95) than in men (odds ratio, 1.38; 95% confidence interval, 0.85-2.34).
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Overall 75 patients with rheumatic mitral heart disease were examined for the effect of the clinical and echocardiography characteristics of central and intracardiac hemodynamics on the efficacy of the use of digoxin. The development of digoxin resistance in patients with the predominance of stenosis of the mitral opening depended to the greatest degree on the duration of heart decompensation, area of the mitral opening and duration of the phase of left ventricle relaxation; in patients with the predominance of mitral insufficiency, it depended on the level of endosystolic stress, pressure of left ventricle filling and duration of the phase of isometric left ventricle contraction. Based on the calculation of the information content of the parameters under study, a prognostic table was made. The use of the table allowed forecasting the development of glycoside resistance in 77.6% of cases.
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Studies in the fetal lamb have shown that atrial pacing beyond a rate of 300-320 beats/min may be associated with dramatic changes of venous blood velocity waveforms, an increase of venous pressure by up to 75%, hydrops, polyhydramnios and placental edema. The aim of our study was to determine the 'critical' heart rate frequency in the human fetus. In 11 fetuses (five with and six without hydrops) with supraventricular tachycardia, pulsed wave Doppler analysis of flow velocity waveforms of the inferior vena cava, the ductus venosus and the left hepatic vein were performed before and after drug treatment. In ten cases cardioversion was achieved by in utero antiarrhythmic drug therapy; in one case treated with digoxin and flecainide the supraventricular tachycardia was decreased to 160-190 beats/min with disappearance of hydrops. Before intrauterine treatment of supraventricular tachycardia, pulsatile reversal of blood flow in the inferior vena cava, ductus venosus and left hepatic vein was visible, with monophasic forward flow during systole and reversed flow during diastole in ten of 11 fetuses. One fetus with supraventricular tachycardia of 195 beats/min showed a normal biphasic forward flow pattern. During drug-induced sinus rhythm, a normal biphasic forward venous blood flow pattern was shown in all ten cases. In five cases pulsatile reversal was demonstrated during a drug-induced reduction of the heart rate from 280 to 210 beats/min and a normal biphasic forward flow velocity waveform appeared during supraventricular tachycardia below 210 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)
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As compared with the conventional therapy and the use of each drug alone, a combination of the ACEI enalapril and the AT1-antagonist losartan promotes a more significant increase in the satisfaction of the patients with their vital activity, in the critical rate of their self-assessment of the "internal picture" of disease, and leads to a greater improvement of the quality of their life as a whole.
In this article, we review the current literature regarding the pathophysiology and management of RIP and discuss the risks and benefits associated with each option, which includes ketoconazole (KTZ), 5-α-reductase inhibitors and other hormonal therapies, phosphodiesterase type 5 (PDE5) inhibitors, intracavernosal sympathomimetic injection, oral sympathomimetic agents, and other investigational therapies.
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A prospective, observational study of 1318 consecutive anticoagulated patients with nonvalvular atrial fibrillation, recruited between June 2013 and March 2014. We analyzed the patients' general characteristics, management, and antiarrhythmic therapy.
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To compare the effects of ACE inhibitors and digoxin on 1-year mortality, morbidity, and physical function among patients aged 85 years.
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Limited to English-language journals with no limitation set on the year of publication for clinical trials, meta-analyses, and reviews.
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Hawthorn is an herb indicated for treating cardiac illness. Because a patient taking digoxin may also take hawthorn, we investigated potential interference of hawthorn in serum digoxin measurements using immunoassays as well as pharmacodynamic interaction between hawthorn and digoxin. Hawthorn contains alkaloids that are structurally similar to digoxin and may interfere with serum digoxin measurement using immunoassays. In addition, hawthorn has cardioactive properties similar to digoxin.