Point mutations of ATP-binding cassette (ABC) proteins are a common cause of human diseases. Available crystal structures indicate a similarity in the architecture of several members of this protein family. Their molecular architecture makes these proteins vulnerable to mutation, when critical structural elements are affected. The latter preferentially involve the two transmembrane domain (TMD)...

Inhibition of drug efflux pumps such as P-glycoprotein represents a versatile approach for overcoming multidrug resistance in tumor therapy. Although numerous compounds have been identified as being able to inhibit P-glycoprotein, only little is known on the molecular basis of the drug–protein interaction. This article gives an overview of the different pharmacoinformatic approaches we used to ...

successful internal cardioversion, and its prevention by intravenous sotalol. Heart 1999; 82: 319–24. [16] Bianconi L, Mennuni M, Lukic V, Castro A, Chieffi M, Santini M. Effects of oral propafenone administration before cardioversion of chronic atrial fibrillation: a placebocontrolled study. J Am Coll Cardiol 1996; 28: 700–6. [17] Capucci A, Villani GQ, Aschieri D, Rosi A, Piepoli MF. Oral ami...

Three cases are presented who died suddenly while being continuously monitored on ambulatory Holter ECG. Two patients with coronary artery disease and severe left ventricular dysfunction after multiple myocardial infarctions died instantly from ventricular fibrillation; this was preceded by a rapid uniform ventricular tachycardia in one patient with normal Q-T interval and by polymorphous ventr...

In this study, we tested a series of 12 previously identified, highly effective propafenone-type multidrug resistance (MDR) modulators for their possible undesirable effects on cardiac tissue. We used rat papillary muscle preparations and quantitatively determined the potency of these substances to block action potential (AP) upstroke velocity (Vmax) and to prolong APD50. Simultaneously, the ef...

Management (AFFIRM) trial, which may shed indirect light on the merit of use of amiodarone on the grounds of its superior efficacy. On the other hand, a longer duration of follow-up would allow sufficient time for development of amiodarone organ toxicity with its attendant significant costs. The major adverse effects of sotalol and propafenone are predominantly seen early in the treatment cours...