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1.

001-es BibID:BIBFORM001011
Első szerző:Bányász Tamás (élettanász)
Cím:Action potencial clamp fingerprints of K+ currents in canine cardiomyocytes : their role in ventricular repolarization / Bányász T., Magyar J., Szentandrássy N., Horváth B., Birinyi P., Szentmiklósi J., Nánási P.
Dátum:2007
Megjegyzések:The aim of the present study was to give a parametric description of the most important K(+) currents flowing during canine ventricular action potential. METHODS: Inward rectifier K(+) current (I(K1)), rapid delayed rectifier K(+) current (I(Kr)), and transient outward K(+) current (I(to)) were dissected under action potential clamp conditions using BaCl(2), E-4031, and 4-aminopyridine, respectively. RESULTS: The maximum amplitude of I(to) was 3.0 +/- 0.23 pA/pF and its integral was 29.7 +/- 2.5 fC/pF. The current peaked 4.4 +/- 0.7 ms after the action potential upstroke and rapidly decayed to zero with a time constant of 7.4 +/- 0.6 ms. I(Kr) gradually increased during the plateau, peaked 7 ms before the time of maximum rate of repolarization (V(max)(-)) at -54.2 +/- 1.7 mV, had peak amplitude of 0.62 +/- 0.08 pA/pF, and integral of 57.6 +/- 6.7 fC/pF. I(K1) began to rise from -22.4 +/- 0.8 mV, peaked 1 ms after the time of V(max)(-) at -58.3 +/- 0.6 mV, had peak amplitude of 1.8 +/- 0.1 pA/pF, and integral of 61.6 +/- 6.2 fC/pF. Good correlation was observed between peak I(K1) and V(max)(-) (r = 0.93) but none between I(Kr) and V(max)(-). Neither I(K1) nor I(Kr) was frequency-dependent between 0.2 and 1.66 Hz. Congruently, I(Kr) failed to accumulate in canine myocytes at fast driving rates. CONCLUSION: Terminal repolarization is dominated by I(K1), but action potential duration is influenced by several ion currents simultaneously. As I(to) was not active during the plateau, and neither I(K1) nor I(Kr) was frequency-dependent, other currents must be responsible for the frequency dependence of action potential duration at normal and slow heart rates in canine ventricular cells.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Acta Physiologica (Oxford, England). - 190 : 3 (2007), p. 189-198. -
További szerzők:Magyar János (1961-) (élettanász) Szentandrássy Norbert (1976-) (élettanász) Horváth Balázs (1981-) (élettanász) Birinyi Péter (1981-) (élettanász) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Nánási Péter Pál (1956-) (élettanász)
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2.

001-es BibID:BIBFORM013054
Első szerző:Harmati Gábor (élettanász)
Cím:Effects of β-adrenoceptor stimulation on delayed rectifier K(+) currents in canine ventricular cardiomyocytes / Harmati G., Bányász T., Bárándi L., Szentandrássy N., Horváth B., Szabó G., Szentmiklósi J., Szénási G., Nánási P., Magyar J.
Dátum:2011
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
isoproterenol
beta adrenerg
canine
cardiomyocyte
ionic current
Megjelenés:British Journal of Pharmacology. - 162 : 4 (2011), p. 890-896. -
További szerzők:Bányász Tamás (1960-) (élettanász) Bárándi László (1984-) (élettanász) Szentandrássy Norbert (1976-) (élettanász) Horváth Balázs (1981-) (élettanász) Szabó G. (orvos) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Szénási Gábor Nánási Péter Pál (1956-) (élettanász) Magyar János (1961-) (élettanász)
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3.

001-es BibID:BIBFORM030263
035-os BibID:WOS:000168774300010
Első szerző:Jednákovits Andrea
Cím:In vivo and in vitro acute cardiovascular effects of bimoclomol / Andrea Jednákovits, Péter Ferdinándy, László Jaszlits, Tamás Bányász, János Magyar, Péter Szigligeti, Ágnes Körtvély, József A. Szentmiklósi, Péter P. Nánási
Dátum:2000
ISSN:0306-3623
Megjegyzések:Effects of bimoclomol, the novel heat shock protein (HSP) coinducer, was studied in various mammalian cardiac and rabbit aortic preparations. Bimoclomol decreased the ST-segment elevation induced by coronary occlusion in anesthetized dogs (56% and 80% reduction with 1 and 5 mg/kg, respectively). In isolated working rat hearts, bimoclomol increased coronary now (CF), decreased the reduction of cardiac output (CO) and left ventricular developed pressure (LVDP) developing after coronary occlusion, and prevented ventricular fibrillation (VF) during reperfusion. In rabbit aortic preparations, precontracted with phenylephrine, bimoclomol induced relaxation (EC50=214 muM). Bimoclomol produced partial relaxation against 20 mM KCl, however, bimoclomol failed to relax preparations precontracted with serotonin, PGF(2) or angiotensin II. All these effects were evident within a few minutes after application of bimoclomol. A rapid bimoclomol-induced compartmental translocation of the already preformed HSPs may explain the protective action of the compound. (C) 2001 Elsevier Science Inc. All rights reserved.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:General Pharmacology-the Vascular System. - 34 : 5 (2000), p. 363-369. -
További szerzők:Ferdinándy Péter Jaszlits László Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Szigligeti Péter Körtvély Ágnes Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Nánási Péter Pál (1956-) (élettanász)
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4.

001-es BibID:BIBFORM030267
Első szerző:Körtvély Ágnes
Cím:Cardiovascular effects of BRX-005 comparison to bimoclomol / Ágnes Körtvély, Gyula Szigeti, Rudolf Gesztelyi, Judit Zsuga, Tamás Bányász, János Magyar, Péter Szigligeti, László Kovács, Andrea Jednákovits, A. József Szentmiklósi, Péter P. Nánási
Dátum:2000
ISSN:0024-3205
Megjegyzések:Concentration-dependent effects of BRX-005, the novel heat shock protein coinducer, cardioprotective and vasoprotective agent, on intracellular calcium transients and contractility were studied in Langendorff-perfused guinea pig hearts loaded with the fluorescent calcium indicator dye Fura-2. BRX-005 increased peak left ventricular pressure, the rate of force development and relaxation significantly in a concentration-dependent manner. The amplitude of [Ca2+](i) transients was left unaltered by the drug, in contrast to BRX-005, bimoclomol increased both contractility and the amplitude of [Ca2+](i) transients, In canine ventricular cardiomyocytes high concentrations of BRX-005 had no effect on depolarization, whereas bimoclomol suppressed action potential upstroke markedly. In guinea pig pulmonary artery preparations precontracted with phenylephrine, BRX-005 induced concentration-dependent relaxation. This effect of BRX-005 was independent of the integrity of endothelium indicating that vasorelaxant effect of the drug develops directly on vascular smooth muscle, (C) 2000 Elsevier Science Inc. All rights reserved.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Life Sciences. - 67 : 14 (2000), p. 1783-1789. -
További szerzők:Szigeti Gyula (1969-) (élettanász, elektrofiziológus) Gesztelyi Rudolf (1969-) (kísérletes farmakológus) Zsuga Judit (1973-) (neurológus, pszichoterapeuta, egészségügyi szakmanager) Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Szigligeti Péter Kovács László (1939-) (élettanász) Jednákovits Andrea Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Nánási Péter Pál (1956-) (élettanász)
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5.

001-es BibID:BIBFORM017197
Első szerző:Szentandrássy Norbert (élettanász)
Cím:Powerful technique to test selectivity of agents acting on cardiac ion channels : the action potential voltage-clamp / Norbert Szentandrássy, Dénes Nagy, Ferenc Ruzsnavszky, Gábor Harmati, Tamás Bányász, János Magyar, A. József Szentmiklósi, Péter P. Nánási
Dátum:2011
ISSN:0929-8673
Megjegyzések:Action potential voltage-clamp (APVC) is a technique to visualize the profile of various currents during the cardiacaction potential. This review summarizes potential applications and limitations of APVC, the properties of the mostimportant ion currents in nodal, atrial, and ventricular cardiomyocytes. Accordingly, the profiles ("fingerprints") of themajor ion currents in canine ventricular myocytes, i.e. in cells of a species having action potential morphology and setof underlying ion currents very similar to those found in the human heart, are discussed in details. The degree ofselectivity of various compounds, which is known to be a critical property of drugs used in APVC experiments, isoverviewed. Thus the specificity of agents known to block sodium (tetrodotoxin, saxitoxin), potassium (chromanol293B, HMR 1556, E-4031, dofetilide, sotalol, 4-aminopyridine, BaCl2), calcium (nifedipine, nisolpidine, nicardipine,diltiazem, verapamil, gallopamil), and chloride (anthracene-9-carboxylic acid, DIDS) channels, the inhibitor of thesodium-calcium exchanger (SEA0400), and the activator of sodium current (veratridine) are accordingly discussed.Based on a theory explaining how calcium current inhibitors block calcium channels, the structural comparison of thestudied substances usually confirmed the results of the literature. Using these predictions, a hypothetical super-selectivecalcium channel inhibitor structure was designed. APVC is a valuable tool not only for studying the selectivity of theknown ion channel blockers, but is also suitable for safety studies to exclude cardiac ion channel actions of any agentunder development.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
action potential
action potential voltage-clamp
Molekuláris Medicina
calcium channel
chemical structure
ion current
ion channel blocker
Molekuláris Medicina
selective calcium channel blocker
Megjelenés:Current Medicinal Chemistry. - 18 : 24 (2011), p. 3737-3756. -
További szerzők:Nagy Dénes (1984-) (vegyész) Ruzsnavszky Ferenc (1984-) (élettanász) Harmati Gábor (1983-) (élettanász) Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Nánási Péter Pál (1956-) (élettanász)
Pályázati támogatás:K 73160
OTKA
CNK 77855
OTKA
K 68457
OTKA
TáMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
A feszültségfüggő K-csatornák szerepe excitábilis sejtekben
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6.

001-es BibID:BIBFORM056832
Első szerző:Szentmiklósi József András (farmakológus, klinikai laboratóriumi szakorvos)
Cím:Chemistry, physiology, and pharmacology of [béta]-adrenergic Mechanisms in the heart : why are [béta]-blocker antiarrhythmics superior? / József A. Szentmiklósi, Norbert Szentandrássy, Bence Hegyi, Balázs Horváth, János Magyar, Tamás Bányász, Péter P. Nánási
Dátum:2015
ISSN:1381-6128
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
[béta]-adrenergic receptors
[béta]-receptor blockers
proarrhythmic mechanisms
antiarrhythmic drugs
cardiac ion currents
cardiac remodeling
Megjelenés:Current Pharmaceutical Design. - 21 : 8 (2015), p. 1030-1041. -
További szerzők:Szentandrássy Norbert (1976-) (élettanász) Hegyi Bence (1987-) (élettanász) Horváth Balázs (1981-) (élettanász) Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Nánási Péter Pál (1956-) (élettanász)
Pályázati támogatás:OTKA-K100151
OTKA
OTKA-PD101171
OTKA
OTKA-K101196
OTKA
OTKA-K109736
OTKA
OTKA-NK104331
OTKA
TÁMOP-4.2.2.A-11/1/KONV-2012-0045
TÁMOP
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7.

001-es BibID:BIBFORM056739
Első szerző:Szentmiklósi József András (farmakológus, klinikai laboratóriumi szakorvos)
Cím:The janus face of adenosine : antiarrhythmic and proarrhythmic actions / A. József Szentmiklósi, Zoltán Galajda, Ágnes Cseppentő, Rudolf Gesztelyi, Zsolt Susán, Bence Hegyi, Péter P. Nánási
Dátum:2015
ISSN:1381-6128
Megjegyzések:Adenosine is a ubiquitous, endogenous purine involved in a variety of physiological and pathophysiological regulatory mechanisms. Adenosine has been proposed as an endogenous antiarrhythmic substance to prevent hypoxia/ischemia-induced arrhythmias. Adenosine (and its precursor, ATP) has been used in the therapy of various cardiac arrhythmias over the past six decades. Its primary indication is treatment of paroxysmal supraventricular tachycardia, but it can be effective in other forms of supraventricular and ventricular arrhythmias, like sinus node reentry based tachycardia, triggered atrial tachycardia, atrioventricular nodal reentry tachycardia, or ventricular tachycardia based on a cAMP-mediated triggered activity. The main advantage is the rapid onset and the short half life (1- 10 sec). Adenosine exerts its antiarrhythmic actions by activation of A1 adenosine receptors located in the sinoatrial and atrioventricular nodes, as well as in activated ventricular myocardium. However, adenosine can also elicit A2A, A2B and A3 adenosine receptor-mediated global side reactions (flushing, dyspnea, chest discomfort), but it may display also proarrhythmic actions mediated by primarily A1 adenosine receptors (e.g. bradyarrhythmia or atrial fibrillation). To avoid the non-specific global adverse reactions, A1 adenosine receptor- selective full agonists (tecadenoson, selodenoson, trabodenoson) have been developed, which agents are currently under clinical trial. During long-term administration with orthosteric agonists, adenosine receptors can be internalized and desensitized. To avoid desensitization, proarrhythmic actions, or global adverse reactions, partial A1 adenosine receptor agonists, like CVT-2759, were developed. In addition, the pharmacologically "silent" site- and event specific adenosinergic drugs, such as adenosine regulating agents and allosteric modulators, might provide attractive opportunity to increase the effectiveness of beneficial actions of adenosine and avoid the adverse reactions.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Adenosinergic drugs
antiarrhythmic action
proarrhythmic effect
adenosine A1 receptor activators
partial A1 adenosine receptor agonists
adenosine regulators
allosteric receptor modulators
drug development
Megjelenés:Current Pharmaceutical Design. - 21 : 8 (2015), p. 965-976. -
További szerzők:Galajda Zoltán (1962-) (szívsebész, érsebész) Cseppentő Ágnes (1953-) (orvos) Gesztelyi Rudolf (1969-) (kísérletes farmakológus) Susán Zsolt (1983-) (sebész) Hegyi Bence (1987-) (élettanász) Nánási Péter Pál (1956-) (élettanász)
Pályázati támogatás:TÁMOP-4.2.2.A-11/1/KONV-2012-0045
TÁMOP
Sebészet Kutatócsoport
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8.

001-es BibID:BIBFORM020347
035-os BibID:WOS:000294414700008
Első szerző:Szentmiklósi József András (farmakológus, klinikai laboratóriumi szakorvos)
Cím:Xanthine derivatives in the heart : blessed or cursed? / Szentmiklosi A. J., Cseppento A., Gesztelyi R., Zsuga J., Kortvely A., Harmati G., Nanasi P. P.
Dátum:2011
ISSN:0929-8673
Megjegyzések:Methylxanthines, such as theophylline, have been used to treat cardiorespiratory disorders, whereas caffeine is the most widely consumed psychoactive agent in various soft drinks. Because of the worldwide use of these drugs and the recently synthesized xanthine derivatives, an intensive research on the cardiac actions of these substances is under progress. This review focuses on the molecular mechanisms involved in the actions of xanthine derivatives with special reference to their adenosine receptor antagonistic properties. The main basic and human studies on the action of xanthines on impulse initiation and conduction, as well as the electrophysiological and mechanical activity of the working myocardium will be overviewed. The potential beneficial and harmful actions of the methylxanthines will be discussed in light of the recent experimental and clinical findings. The pharmacological features and clinical observations with adenosine receptor subtype-specific xanthine antagonists are also the subject of this paper. Based on the adenosine receptor-antagonistic activity of these compounds, it can be raised that xanthine derivatives might inhibit the cardioprotective action of endogenous adenosine on various subtypes (A(1), A(2A), A(2B) and A(3)) of adenosine receptors. Adenosine is an important endogenous substance with crucial role in the regulation of cardiac function under physiological and pathological conditions (preconditioning, postconditioning, ischemia/reperfusion injury). Recent clinical studies show that acute administration of caffeine or theophylline can inhibit various types of preconditioning in human subjects. There are no human studies, however, for the cardiovascular actions of long-term administration of these drugs. Upregulation of adenosine receptors and increased effectiveness of adenosine receptor-related cardiovascular functions have been observed after long-lasting treatment with methylxanthines. In addition, there are data indicating that blood adenosine level increases after long-term caffeine administration. Since the salutary actions (and also the adverse reactions) of a number of xanthine derivatives are repeatedly shown, the main goal is the development of novel structures that mimic the actions of the conventional methylxanthines as lead compounds, but their adenosine receptor subtype-specificity is higher, their water solubility is optimal, and the unwanted reactions are minimized.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Current Medicinal Chemistry. - 18 : 24 (2011), p. 3695-3706. -
További szerzők:Cseppentő Ágnes (1953-) (orvos) Gesztelyi Rudolf (1969-) (kísérletes farmakológus) Zsuga Judit (1973-) (neurológus, pszichoterapeuta, egészségügyi szakmanager) Körtvély Ágnes Harmati Gábor (1983-) (élettanász) Nánási Péter Pál (1956-) (élettanász)
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9.

001-es BibID:BIBFORM016601
Első szerző:Szentmiklósi József András (farmakológus, klinikai laboratóriumi szakorvos)
Cím:Novel trends in the treatment of cardiovascular disorders : site- and event- selective adenosinergic drugs. / Szentmiklósi A. J., Cseppento A., Harmati G., Nánási P. P.
Dátum:2011
ISSN:0929-8673
Megjegyzések:This review focuses on the potential role of site- and event-selective adenosinergic drugs in the treatment of cardiovascular diseases. Adenosine is released from the myocardium and vessels in response to various forms of stress and acts on four receptor subtypes (A1, A2A, A2B and A3). Adenosine is an important endogenous substance with important homeostatic activity in the regulation of cardiac function and circulation. Adenosine receptors are also involved in the modulation of various cellular events playing crucial role in physiological and pathological processes of the cardiovascular system. These actions are associated to activation of distinct adenosine receptor subtypes, therefore drugs targeting specific adenosine receptors might be promising therapeutic tools in treatment of several disorders including various forms of cardiac arrhythmia, myocardial ischemia-reperfusion injury, angina pectoris, chronic heart failure, etc. Recently, in addition to subtype-specific adenosine receptor agonists and antagonists, a number of substances that enhance adenosine receptor activation locally at the site where the release of endogenous adenosine is the most intensive have been developed. Thus global actions of adenosine receptor agonists and antagonists, as well as desensitization or down-regulation following chronic administration of these orthosteric compounds can possibly be avoided. We discuss the chemical, pharmacological and clinical features of these compounds: (1) inhibitors of membrane adenosine transporters (NBTI, dipyridamole), (2) inhibitors of adenosine deaminase (coformycin, EHNA), (3) inhibitors of adenosine kinase (tubercidin, aristeromycin), (4) inhibitors of AMP deaminase (GP3269), (5) activators of 5'- nucleotidase (methotrexate), (6) adenosine regulators (acadesine) and (7) allosteric adenosine receptor modulators (PD81723, LUF6000). The development of this type of substances might offer a novel therapeutic approach for treating cardiovascular diseases in the near future.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Site and event specific action
adenosinergic drugs
membrane adenosine transport
adenosine deaminase
adenosine kinase
AMP deaminase
5'-nucleotidase
adenosine regulators
allosteric receptor modulators
Megjelenés:Current Medicinal Chemistry. - 18 : 8 (2011), p. 1164-1187. -
További szerzők:Cseppentő Ágnes (1953-) (orvos) Harmati Gábor (1983-) (élettanász) Nánási Péter Pál (1956-) (élettanász)
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