Regulation of gap junction function; the role of nitric oxide.

Myocardial ischemia resulting from sudden occlusion of a coronary artery is one of the major causes in the appearance of severe, often life-threatening ventricular arrhythmias. Although the underlying mechanisms of these acute arrhythmias are many and varied, there is no doubt that uncoupling of gap junctions (GJs) play an important role especially in arrhythmias that are generated during phase Ib, and often terminate in sudden cardiac death. In the past decades considerable efforts have been made to explore mechanisms which regulate the function of GJs, and to find new approaches for protection against arrhythmias through the modulation of GJs. These investigations led to the development of GJ openers and inhibitors. The pharmacological modulation of GJs, however, resulted in conflicting results. It is still not clear whether opening or closing of GJs would be advantageous for the ischemic myocardium. Both maneuvers can result in protection, depending on the models, endpoints and the time of opening and closing of GJs. Furthermore, although there is substantial evidence that preconditioning decreases or delays the uncoupling of GJs, the precise mechanisms by which this attains have not yet been elucidated. In our own studies in anesthetized dogs preconditioning suppressed the ischemia and reperfusion-induced ventricular arrhythmias, and this protection was associated with the preservation of GJ function, manifested in less marked changes in electrical impedance, as well as in the maintenance of GJ permeability and phosphorylation of connexin43. Since we have substantial previous evidence that nitric oxide (NO) is an important trigger and mediator of the preconditioning-induced antiarrhythmic protection, we hypothesized that NO, among its several effects, may lead to this protection by influencing cardiac GJs. The hypotheses and theories relating to the pharmacological modulation of GJs will be discussed with particular attention to the role of NO

Analysis of the amino acid composition of pollen and honey

Nowadays, an important direction in food analytical research is the development of methods for detecting honey counterfeiting. The amino acids in honey come mainly from pollen, raising the possibility of origin determination based on the examination of amino acid composition [1]. In our research, the free amino acid composition of single flower honeys and the pollen from their original plants were compared. According to our results, there is no correlation between the amino acid profiles of the pollen and the honeys, which is mainly due to the fact that it is rare that the pollen composition of single flower honeys strongly reflects the flower character. Our results support the hypothesis that proline comes from the bees, and the proline content of the pollen contributes to the high proline content of honey only marginally. Pollen pellet samples also contain large amounts of nectar and glandular secretions in addition to the pollen, and thus have a significantly lower free amino acid content than pollen samples collected directly from the flowers. In the course of the research, the total amino acid content of the pollen pellets was in the 6 to 16% range. Compared to other amino acids, proline was present in a significantly higher proportion in the free form than in the protein-bound form. There are contradictory data in the literature regarding the ability of bees to select among different pollens according to their needs [2, 3]. According to our results, the amino acid composition of pellets selected by the bees reflects their amino acid requirements better than unifloral samples. The rapeseed pellet, which is particularly preferred by the bees, has an amino acid composition that is different from the optimal one, but it has an outstanding essential amino acid content, so it is likely that a quantitative, and not qualitative protein intake regulation is carried out by the bees

Szívvédelem szervetlen nitrátokkal = Cardioprotection with inorganic nitrites

Le temps est l'objet de conflits, dont une bonne part se déroule au sein des organisations de travail. Tel est le point de départ de ce numéro. La lutte, ancienne et bien documentée, entre employeurs et salariés est évidemment au cœur du problème. Son histoire est longue et constitue l’un des éléments à la base même du salariat : la délimitation du temps dévolu au travail, les méthodes de mesure, la régulation des temps de non-travail, etc. ont tous causé des combats acharnés qui se sont trad..

Antiarrhythmiás hatású mechanizmusok in vivo és in vitro tanulmányozása = In vivo and in vitro analysis of antiarrhythmic mechanisms

Az aritmiák csökkentésére irányuló korábbi munkánk folytatásaként a 2008-2012 kutatási periódusban a következő eredményeket értük el. A gap junkciós (GJ) csatornák szerepét vizsgálva kimutattuk, hogy ezen csatornák iszkémia alatti nyitása és zárása is, paradox módon, csökkenti az iszkémia/reperfúzió okozta kamrai aritmiákat. Elsőként közöltük, hogy a prekondicionálás egyik fő mediátoraként tekintett nitrogén monoxid (NO), a szívizom GJ csatornáit is módosítani képes; in vivo és in vitro kísérleteink eredményei igazolták, hogy a szerves és szervetlen nitritekből származó NO gátolja a GJ csatornák szétkapcsolását és az aritmiák kialakulását. Igazoltuk a GJ csatornák szerepét a szívingerléssel kiváltott késői védőhatásban rámutatva arra, hogy a gyors szívingerlés időfüggő változást okoz mind a GJ csatornákat felépítő Cx43 gén és fehérje, mind más olyan egyéb gének expressziójában, amelyek a késői védőhatás kialakulásáért felelős fehérjéket kódolnak. A NO és a ROS kardioprotekcióban játszott szerepét vizsgáló kísérleteinkben kimutattuk, hogy az iszkémia okozta csökkent NO képződés fokozza az aritmiákat és bármilyen olyan beavatkozás, amely a NO hozzáférhetőségét helyreállítja védőhatású lehet. Kísérleteinkben a nátrium nitrit infúziója jelentős mértékben csökkentette az aritmiákat feltehetően a fehérjék S-nitrozilációja és a ROS-képződés NO általi gátlása révén. A projekt sikeres teljesítését Ph.D. hallgatók és asszisztensek munkája, és az OTKA támogatása tette lehetővé. | Continuing our previous research on protection against arrhythmias our achievements between 2008 and 2012 were as the follows. In studies, aiming to explore the role of gap junctions (GJ), we have shown that the pharmacological modulation of GJs using either GJ openers or blockers reduces arrhythmias, resulting from ischaemia and reperfusion. We were the first to propose that nitric oxide (NO), a key mediator of the preconditioning-induced protection modifies myocardial GJ function. Studies in vivo and in vitro have revealed that both organic and inorganic NO donors attenuate the uncoupling of GJs and this effect plays a role in the protection. We have also shown that GJs are involved in the delayed antiarrhythmic effect of cardiac pacing. Rapid pacing induces time-dependent changes in Cx43 gene and protein expressions, and in the translation of many other genes, encoding proteins involved in the late phase of the protection. In studies, aiming to explore the role of NO and reactive oxygen species (ROS) in cardioprotection, we have found that the ischaemia-induced loss in NO production leads to increased arrhythmia generation and that any manoeuvre which increases NO availability, would result in protection. Sodium nitrite has been found to reduce arrhythmias via the regulation of ROS production and protein S-nitrosylation. The work of young scientists and technical assistants, and the support of the OTKA are largely contributed to the successful completion of the project

Virágporok és mézek aminosav-összetételének vizsgálata

Nowadays, an important direction in food analytical research is the development of methods for detecting honey counterfeiting. The amino acids in honey come mainly from pollen, raising the possibility of origin determination based on the examination of amino acid composition [1]. In our research, the free amino acid composition of single flower honeys and the pollen from their original plants were compared. According to our results, there is no correlation between the amino acid profiles of the pollen and the honeys, which is mainly due to the fact that it is rare that the pollen composition of single flower honeys strongly reflects the flower character. Our results support the hypothesis that proline comes from the bees, and the proline content of the pollen contributes to the high proline content of honey only marginally. Pollen pellet samples also contain large amounts of nectar and glandular secretions in addition to the pollen, and thus have a significantly lower free amino acid content than pollen samples collected directly from the flowers. In the course of the research, the total amino acid content of the pollen pellets was in the 6 to 16% range. Compared to other amino acids, proline was present in a significantly higher proportion in the free form than in the protein-bound form. There are contradictory data in the literature regarding the ability of bees to select among different pollens according to their needs [2, 3]. According to our results, the amino acid composition of pellets selected by the bees reflects their amino acid requirements better than unifloral samples. The rapeseed pellet, which is particularly preferred by the bees, has an amino acid composition that is different from the optimal one, but it has an outstanding essential amino acid content, so it is likely that a quantitative, and not qualitative protein intake regulation is carried out by the bees. © 2019, Wessling International Research and Educational Centre Nonprofit Beneficial Ltd. All rights reserved

Examination of the effect of sodium nitrite on gap junction function during ischaemia and reperfusion in anaesthetized dogs

It has previously been proved that sodium nitrite, infused prior to coronary artery occlusion or before reperfusion, results in marked antiarrhythmic effect in anaesthetized dogs. We have now examined whether this protection involves the modulation of gap junction (GJ) function by nitric oxide (NO), derived from nitrite administration under ischaemic conditions. Two groups of chloralose and urethane anaesthetized dogs, each containing 13 animals, were subjected to a 25 min period occlusion of the left anterior descending (LAD) coronary artery, followed by reperfusion. One group was infused with sodium nitrite (0.2 μmol/kg/min, i.v.), the other group with saline 10 min prior to reperfusion. The severities of arrhythmias and of ischaemia (epicardial ST-segment, total activation time), parallel with changes in myocardial tissue impedance, a measure of electrical coupling of gap junctions, were assessed during the experiments. Compared to the controls, nitrite infusion administered prior to reperfusion significantly attenuated the severity of ischaemia, the ischaemia-induced impedance changes and, consequently, the severity of arrhythmias, occurring during the 1B phase of the occlusion, and increase survival following reperfusion (0% vs. 85%). It is concluded that the marked antiarrhythmic effect of sodium nitrite is partly due, to the preservation of the electrical coupling of GJs by NO