High blood pressure. Causes, symptoms, treatments

Antimicrobial resistance profile of Enterococcus species isolated from intestinal tracts of hospitalized patients in Jimma, Ethiopia.


In this study, a beta-adrenergic blocker in combination with digoxin provided marginal protection against atrial fibrillation/flutter after coronary artery surgery. The economic comparison of patients who did and did not develop atrial fibrillation/flutter indicates that prevention of these arrhythmias can have a significant impact on length of hospital stay and cost of this common surgical procedure.

The population pharmacokinetics parameters of levosimendan in this patient group were comparable to those obtained by traditional methods in healthy volunteers and patients with mild heart failure. Bodyweight influenced the clearance and the central volume of distribution, which in practice is accounted for by weight adjusting doses. None of the other covariates, including digoxin and beta-blocking agents, significantly influenced the pharmacokinetics of levosimendan.

Cardiac glycosides (CGs), prescribed to treat cardiovascular alterations, display potent anti-cancer activities. Despite their well-established target, the sodium/potassium (Na(+)/K(+))-ATPase, downstream mechanisms remain poorly elucidated. UNBS1450 is a hemi-synthetic cardenolide derived from 2″-oxovorusharin extracted from the plant Calotropis procera, which is effective against various cancer cell types with an excellent differential toxicity. By comparing adherent and non-adherent cancer cell types, we validated Mcl-1 as a general and early target of UNBS1450. A panel of CGs including cardenolides ouabain, digitoxin and digoxin as well as bufadienolides cinobufagin and proscillaridin A allowed us to generalize our findings. Our results show that Mcl-1, but not Bcl-xL nor Bcl-2, is rapidly downregulated prior to induction of apoptosis. From a mechanistic point of view, we exclude an effect on transcription and demonstrate involvement of a pathway affecting protein stability and requiring the proteasome in the early CG-induced Mcl-1 downregulation, without the involvement of caspases or the BH3-only protein NOXA. Strategies aiming at preventing UNBS1450-induced Mcl-1 downregulation by overexpression of a mutated, non-ubiquitinable form of the protein or the use of the proteasome inhibitor MG132 inhibited the compound's ability to induce apoptosis. Altogether our results point at Mcl-1 as a ubiquitous factor, downregulated by CGs, whose modulation is essential to achieve cell death.

To determine the proportion of patients newly initiated on selected cardiovascular medications with baseline assessment and follow-up laboratory monitoring and compare the prevalence of laboratory testing for drugs with and without BBWs and guidelines.

Quinidine is known to reduce the renal clearance of digoxin, but this effect does not completely explain the influence of quinidine on the total clearance of digoxin. We therefore studied the effect of quinidine administration on biliary clearance of digoxin in five patients with atrial fibrillation. Biliary clearance of digoxin under steady state conditions before and during treatment with quinidine was investigated using a duodenal-marker-perfusion technique. Quinidine caused an average 42% (range 21-65%, P less than 0.02) reduction of the measured biliary clearance of digoxin. We conclude that the biliary effect adds to the previously demonstrated inhibitory effect of quinidine on the renal clearance of digoxin and helps to explain the decrease in total clearance of the drug. This is the first demonstration in man of a pharmacokinetic drug interaction at the level of biliary excretion.

mRNA expression of eight CYPs and Pgp was investigated in TC7 and parental Caco-2 (Caco-2p) cell monolayers using RT-PCR. The CYP3A kinetics was determined in microsomes from both cell lines. The transport, metabolism and efflux of terfenadine and its metabolites were investigated in TC7 monolayers.

Azimilide is an investigational Class III antiarrhythmic that has been developed for treating both supraventricular and ventricular tachyarrhythmias. Similar to other Class III antiarrhythmics, azimilide prolongs myocardial repolarization in a dose-dependent manner by increasing the action potential duration, QT interval, and effective refractory period. The most frequent reported side effect is headache, with rare serious adverse events of early reversible neutropenia and Torsades de Pointes. In long-term follow up, the patient withdrawal rate has been low. Azimilide has very predictable pharmacokinetics, is predominantly hepatically metabolized, and has no significant drug interactions with digoxin or warfarin. In animal models, azimilide has been shown to be very effective in suppressing both atrial and ventricular tachyarrhythmias, decreasing the defibrillation energy requirement, and preventing post-myocardial infarction ventricular tachycardia and fibrillation. Clinically, in a series of 4 double-blind, randomized, placebo-controlled trials, the Azimilide Supraventricular Arrhythmia Program which included over 1000 patients and approximately 70% with structural heart disease, azimilide showed a significant prolongation in the time to first recurrence of paroxysmal supraventricular tachycardia or atrial fibrillation/flutter. With respect to ventricular tachyarrhythmias, the AzimiLide post-Infarct surVival Evaluation Trial was a large randomized, multinational, prospective, placebo-controlled study in recent survivors of myocardial infarction at high risk for sudden cardiac death. After 1 year of follow-up, this study showed no statistical difference in all-cause mortality between placebo and azimilide. However, azimilide did statistically reduce the incidence of new atrial fibrillation. Further trials are necessary to evaluate the efficacy of azimilide in patients with symptomatic ventricular arrhythmias.