The sodium-calcium exchange (NCX) plays a pivotal role in regulating contractility and electrical activity in the heart. However, the effects of NCX blockers on ventricular arrhythmias are still controversial. We examined the effects of KB-R7943 (KBR) and SEA0400 (SEA), two NCX blockers, on aconitine-induced arrhythmias in guinea pigs using the ECG recordings and the current-clamp method. Using Luo's and Rudy's computer model (1991 Circ Res 68:1501-1526) for ventricular myocytes, we simulated abnormal membrane activity produced by NCX inhibition. In the whole-animal model, KBR in a dose range of 1 to 30 mg/kg (intravenous) suppressed aconitine-induced arrhythmias dose-dependently, but 10 mg/kg of SEA did not suppress these arrhythmias. There was a difference in isolated ventricular myocytes also. KBR (10 M) suppressed abnormal electrical activity induced by aconitine, but SEA (100 M) did not show such effects. KBR (10 M) significantly changed the shape of the action potential configurations (action potential duration at 50% repolarization), but SEA (1-100 M) did not change these configurations. In the computer simulation study, the aconitine-induced abnormal electrical activity was mimicked by a negative shift of the kinetics of Na ϩ channels, and this was followed by additional suppression of NCX activity by 90% (mimicking the effect of NCX inhibitors), which enhanced abnormal membrane activity. Our results indicate that the inhibition of aconitine-induced arrhythmias by KBR, not by SEA, might result from a mechanism other than the inhibition of NCX, and thus the involvement of the NCX system plays an insignificant role in the aconitine-induced arrhythmias.
The research was conducted to investigate the in vitro antimicrobial and cytotoxic activities of leaves and flowers extract extracted from Lippia alba. Disc diffusion technique was used for in vitro antibacterial and antifungal screening. Zones of inhibition were observed in disc diffusion for antibacterial screening against 4 Gram-positive pathogenic and 6 Gram-negative pathogenic bacteria. Among crude extracts chloroform extract showed good activity against all test organisms. A Large zone of inhibition was observed (18 mm) against Vibrio parahaemolyticus. In antifungal screening, the compound showed mild to moderate zones of inhibition against four tested organisms. A Large zone of inhibition was observed against Aspergillus niger (13 mm). Cytotoxic activities of crude extracts were determined using Brine shrimp lethality Bioassay and LC50 values of standard Vincristin sulphate as positive control, n-hexane and crude ethanol extracts were found to be 5, 15 and 20 microg mL(-1), respectively.
The Na + -Ca 2+ exchange (NCX) system plays a pivotal role in regulating intracellular Ca 2+ concentration in cardiomyocytes, neuronal cells, kidney and a variety of other cells. It performs a particularly important function in regulating cardiac contractility and electrical activity. One of the leading NCX inhibitors is KB-R9743 (KBR) that appears to exhibit selectivity for Ca 2+ -influx-mode NCX activity (reverse mode of NCX). In this article we reviewed pharmacology of KBR and provide a brief summary of studies with other NCX inhibitors, such as SEA0400 (SEA) and SN-6 (SN). Potential clinical usefulness of KBR and other NCX inhibitors is still controversial but the reviewed findings may be helpful in designing more selective and clinically useful NCX inhibitors for the treatment of cardiac, neuronal and kidney diseases. the electrogenic movement of 3 Na + ions into and one Ca 2+ ion out of the cells (52,92), thus transporting net one positive charge (inward current) inside the cell per cycle. This movement is called the forward mode or Ca 2+ exit mode or Ca 2+ efflux mode operation of NCX.Under ischemic conditions, however, oxidative phosphorylation rapidly ceases, while anaerobic glycolysis, the net products of which are lactate and protons, is accelerating. This process leads to acidosis that decreases intracellular pH (pH i ). This intracellular acidosis increases [Na + ] i through the Na + -H + exchange (NHE) system or other sources of Na + entry (11). A rise in [Na + ] i , from whatever source, affects NCX by decreasing the driving force for Ca 2+ exit and/or increasing the driving force for Ca 2+ entry. This, in turn, leads to an increases in [Ca 2+ ] i favoring the entry of one Ca 2+ in exchange for 3 Na + ions out of the cells, thus moving net one positive charge (outward current) out of the cells per cycle. This process is called reverse mode, or Ca 2+ entry mode, or Ca 2+ influx mode of the NCX. This process of accumulation of Ca 2+ inside the cells leads to Ca 2+ overload that is observed with ischemia-reperfusion, ouabain-, veratridine-, or aconitine-induced arrhythmias and simulated ischemia in the whole animals, multi-cellular preparations and isolated myocytes of heart, brain or kidney (2)(3)(4)10,15,19,28,33,35,72,91,113,117,123). KBR is regarded as selective inhibitor of reverse mode of NCX. The role of NCX and the effects of KBR in each organ are described in respective sections.The purpose of the present review is to survey the recent progress in the research on a new class of drugs known as NCX inhibitors. KBR is the leading member of this class. This review article covers recent advances in the development and activity of KBR and briefly describes other NCX inhibitors, such as SEA0400 and SN-6. Additional information on NCX and KBR can be found in other reports (10,13,15,21,28,35,85,94,113,116).
Worldwide Internet addiction is a newly emerging mental health and social issue among the youths causing neurological complications, psychological disturbances and social problems. Internet addicts make the Internet urgency more vital than family, friends and work. Several studies exposed that anxiety, backache, blurred vision, dry eyes, headache, sleep disturbance, depression, poor academic performance etc. are results of Internet addiction. Therefore, the objective of this study was to determine the Internet addiction as well as its psychological distress and depression among university undergraduate students of Bangladesh. The study was conducted among 475 students selected from five universities of Bangladesh from July 2015 to September 2015. The selected universities were
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