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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
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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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)
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
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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)
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
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