Efficacy of selective NCX inhibition by ORM-10103 during simulated ischemia/reperfusion.

In this study we evaluated the effects of selective Na+/Ca2+ exchanger (NCX) inhibition by ORM-10103 on the [Ca2+]i transient (CaT), action potential (AP), and cell viability in isolated canine ventricular cardiomyocytes exposed to a simulated ischemia/reperfusion protocol performed either alone (modeling moderate low-flow ischemia) or with simultaneous strophantidine challenge (modeling more severe low-flow ischemia). CaTs were monitored using a Ca2+-sensitive fluorescent dye, APs were recorded by intracellular microelectrodes, and anaerobic shifts in cellular metabolism were verified via monitoring native NADH fluorescence. Simulated ischemia increased the NADH fluorescence, reduced the amplitudes of the AP and CaT and induced membrane depolarization. APs moderately shortened, CaTs prolonged. Diastolic [Ca2+]i ([Ca2+]iD) level increased significantly during ischemia and further elevated following strophantidine application. Reperfusion normalized the NADH level, the amplitude of the AP and duration of the [Ca2+]i transient, but only partially restored action potential triangulation and the amplitude of the CaT. [Ca2+]iD decreased in untreated, but further increased in strophantidine-treated cells. 10microM ORM-10103 significantly reduced the ischemic [Ca2+]i raise in both untreated and strophantidine-treated cells. During reperfusion ORM-10103 decreased [Ca2+]i and eliminated its diastolic elevation in untreated and strophantidine-treated cardiomyocytes. Following the application of ORM-10103 the detrimental effect of ischemia/reperfusion on cell viability and the reperfusion-induced increase in AP and CaT variabilities were substantially reduced, but ischemia-induced shifts in AP morphology were barely influenced. In conclusion, selective NCX inhibition by ORM-10103 is highly effective against ischemia/reperfusion induced pathologic alterations in [Ca2+]i homeostasis, however, it fails to normalize untoward arrhythmogenic changes in AP morphology

Language wants of English majors in a non-native context.

The main aim of our research was to investigate the language wants of English majors in Hungary. First a questionnaire was administered to 279 students at all the six universities of Hungary where there are students majoring in English language and literature combined with TESOL. The participants were mainly students in the last 2 years of their university studies and their number represented approximately 10% of the target population. The same questionnaire was also completed by 80 students who graduated from one of the universities in Hungary in the past 5 years. The design of the questionnaire was informed by the Common European Framework of Reference prepared by the Education Committee of the European Union (Council of Europe, 2001. Common European Framework of Reference for Teaching, Learning and Assessment. Cambridge University Press, Cambridge). The questionnaire was piloted and validated with think-aloud interviews and test–retest reliability analysis. The results suggest that students use English mainly for academic purposes during their university studies. The most important functions for English majors in their future occupation seem to be expressing their opinion, reading texts on the Internet, conversing with non-native speakers, writing e-mail messages, giving explanations and instructions, and translating oral and written English in a variety of occupations. No major differences between students in different years of study and at different universities in the country were found. The methods applied and the findings concerning the needs of English majors in Hungary might also be relevant for other countries with a similar educational system

Investigation of the cardioprotective effect of selective NCX inhibition in cellular models

Cardiovascular diseases are the leading cause of mortality for both men and women worldwide. In many of the cardiac diseases [Ca2+]i overload is a crucial factor in initiation and progression of the malignant intracellular perturbations leading to cell death. A substantial rise in cellular Na+ content is often the primary initiator of the [Ca2+]i overload, leading to arrhythmogenesis. This pathomechanism is also characteristic of ischemia (and especially reperfusion) or arrhythmia types with genetic origin (e.g. LQT3 syndrome). Indeed, [Ca2+]i overload induced arrhythmias are among the most common cardiac diseases. By its regulatory effect on the cytoplasmic Ca2+ the Na+/Ca2+ exchanger (NCX) has a crucial role in the ionic homeostasis of the heart. In physiological conditions its major role is to remove the excess Ca2+, and to stabilize the cellular Ca2+ content and the magnitude and kinetics of the [Ca2+]i transient. Excessive increase in the inward Na+ current may lead to arrhythmogenesis either via [Na+]i induced [Ca2+]i overload or by significantly prolonging the duration of the action potential (APD). The primary aim of the present project was to investigate in detail the effects of [Ca2+]i overload, induced either by increased late Na+ current or by acute ischemia/reperfusion, on characteristic variables of the [Ca2+]i transient (CaT) and action potential (AP), in isolated canine cardiomyocytes. In order to meet our goals we first developed a simulated ischemia/reperfusion model to be used at the cellular level. (There was minimal related information in the literature.) Next, we applied this model to canine cardiomyocytes and investigated the variables of the APs and CaTs recorded from the cells in several experimental states. When applying the protocol “per se”, ischemia/reperfusion induced changes were relatively moderate, therefore this protocol seems to be appropriate to evaluate the effects of moderate ischemia. In order to model more severe ischemia, the sarcolemmal Na+/K+ ATPase was blocked simultaneously. Compared to the low-flow protocol, the observed changes in [Na+]i and [Ca2+]i homeostasis in strophantidine treated cells were much more dramatic during both ischemia and reperfusion. On the whole, tha major results demonstrate that selective NCX inhibition exhibits considerable protection against the arrhythmogenic effect and cell death due to [Ca2+]i overload when induced by increased late sodium current and ischemia/reperfusion