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001-es BibID:	BIBFORM041490
035-os BibID:	(Wos)000251331300008 (Scopus)36349018414
Első szerző:	Brugós László (tüdőgyógyász, klinikai immunológus, allergológus)
Cím:	Modulation of adenosine-induced response in the guinea pig trachea duirng long-term caffeine treatment : possible role of epthelium / László Brugós, Rudolf Gesztelyi, Judit Zsuga, Ágnes Cseppentő, Ilona Benkő, Zoltán Galajda, György Deák, Sándor Sipka, Tamás Rőszer, Péter Kovács, Mária Szilasi, István Édes, András József Szentmiklósi
Dátum:	2007
ISSN:	1347-8613
Megjegyzések:	The responses to adenosine were studied on isolated, methacholine-precontracted tracheal strips of guinea pigs in the course of long-term caffeine or solvent treatment. Guinea pigs were fed caffeine for 10 weeks (average serum caffeine concentration: 39.1 ± 3.9 ?M). In epithelium-intact tracheal preparations (EITPs), sensititization to adenosine-induced relaxation (AIR) developed. It attained a maximum in week 1 of caffeine treatment, and then its level diminished and disappeared completely by weeks 4 - 6. In epithelium-denuded tracheal preparations (EDTPs), an increase in the sensitivity to adenosine was observed from week 1 to week 10 (a 4 - 6-fold reduction in EC50). Use of a coaxial bioassay system confirmed the role of epithelium in this process. The enhancement of the AIR of the EITPs was not modified by inhibitors of cyclooxygenase and lipoxygenase. Following depletion of the neuropeptides by acute capsaicin pretreatment, the AIR of the EITPs was strongly enhanced after caffeine treatment for 6 weeks. In chronically caffeine-treated EITPs, the inhibition of neutral endopeptidase led to dramatic reduction of the AIR. On the basis of the results by inhibiting nitric oxide synthase, it can be supposed that nitric oxide released from EITPs of long-lasting caffeine-treated animals operated as a constrictor agent. Our results show that chronic caffeine treatment gives rise to an initial sensitization to adenosine of the EITPs, this being followed by the development of a specific adaptive process in the epithelial cells, which counterbalances the increased tracheal sensitivity to adenosine.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Journal Of Pharmacological Sciences. - 105 : 3 (2007), p. 279-290. -
További szerzők:	Gesztelyi Rudolf (1969-) (kísérletes farmakológus) Zsuga Judit (1973-) (neurológus, pszichoterapeuta, egészségügyi szakmanager) Cseppentő Ágnes (1953-) (orvos) Benkő Ilona (1954-) (orvos, farmakológus) Galajda Zoltán (1962-) (szívsebész, érsebész) Deák György (1954-) (polimer kémikus) Sipka Sándor (1945-) (laboratóriumi szakorvos) Röszer Tamás (1979-) (orvos, biológus) Kovács Péter (1939-) (farmakológus) Szilasi Mária (1953-) (tüdőgyógyász, klinikai immunológus, allergológus, belgyógyász) Édes István (1952-) (kardiológus) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos)
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001-es BibID:	BIBFORM057912
Első szerző:	Gesztelyi Rudolf (kísérletes farmakológus)
Cím:	Positive inotropic effect of the inhibition of cyclic GMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase (PDE2) on guinea pig left atria in eu- and hyperthyroidism / R. Gesztelyi, J. Zsuga, P. Hajdú, J. Zs. Szabó, A. Cseppentő, A. J. Szentmiklósi
Dátum:	2003
ISSN:	0231-5882
Megjegyzések:	The significance of PDE2 on the atrial inotropy was studied in eu- and hyperthyroidism. The contractile force was measured and negative inotropic capacity of N6-cyclopentyladenosine (CPA) was determined on left atria isolated from 8-day thyroxine- or solvent-treated guinea pigs, in the presence or absence of EHNA (adenosine deaminase and PDE2 inhibitor) or NBTI (nucleoside transporter inhibitor). EHNA was administered to inhibit PDE2, while NBTI was used to model the accumulation of endogenous adenosine. The reduction of the contractile force caused by EHNA was smaller in the thyroxine-treated atria than in the solvent-treated samples. Contrary, NBTI induced a decrease in the contractile force without significant difference between the two groups. In addition, EHNA enhanced the efficiency of CPA in thyroxine-treated atria and did not affect it in solvent-treated samples, while the response to CPA was decreased by NBTI in all atria, especially in hyperthyroidism. On the basis of greater retention of the contractile force and sustained/enhanced responsiveness to CPA in the presence of EHNA we conclude that PDE2's inhibition has a significant positive inotropic effect in guinea pig atria and this effect is proven to be augmented in hyperthyroidism.
Tárgyszavak:	Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	General Physiology and Biophysics. - 22 : 4 (2003), p. 501-513. -
További szerzők:	Zsuga Judit (1973-) (neurológus, pszichoterapeuta, egészségügyi szakmanager) Hajdu Péter (1975-) (biofizikus) Szabó Judit Zsuzsanna (farmakológus, klinikai laboratóriumi szakorvos) Cseppentő Ágnes (1953-) (orvos) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos)
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM028062
Első szerző:	Gesztelyi Rudolf (kísérletes farmakológus)
Cím:	Special sensitization pattern in adenosine-induced myocardial responses after thyroxine-treatment / Gesztelyi Rudolf, Zsuga Judit, Cseppentő Ágnes, Bajza Ágnes, Varga Angelika, Szabó Zs. Judit, Szentmiklósi József A.
Dátum:	2003
Megjegyzések:	Chronic thyroxine treatment reduces the susceptibility of atrial myocardium to adenosine. While the possible role of membrane adenosine receptors in this action is supported by several studies, the involvement of intracellular adenosine mechanisms has not been defined. The present experiments were carried out in electrically driven euthyroid and hyperthyroid guinea pig atrial myocardium. The extracellular and intracellular actions of adenosine were analyzed pharmacologically by the use of specific blockers of membrane adenosine transport and intracellular adenosine deaminase (ADA). The involvement of phosphoprotein phosphatase, phospholamban, and sarcoplasmic reticulum Ca2+ ATPase (SERCA) in the adenosine-induced responses was also studied. The major findings were as follows: i) pD(2)- and E(max)-values for adenosine-induced decrease of mechanical activity were significantly reduced after an 8-day thyroxine treatment in atrial tissues; ii) in atria of thyroxine-treated animals, membrane purine transport inhibitors (dipyridamole, NBTI) induced similar leftward shifts in concentration-response curves for adenosine in both euthyroid and hyperthyroid atrial myocardium without altering the depressed E(max) values; iii) the leftward displacement evoked by inhibitors of intracellularly located ADA (coformycin, EHNA) was more striking in hyperthyroid than euthyroid myocardia. ADA inhibitors induced a complete reversal of the maximum adenosine actions; iv) inhibition by cantharidin of phosphoprotein phosphatases (after inhibition of ADA) reduced the adenosine-induced responses. This inhibition was stronger in hyperthyroid atria; v) pharmacological elimination of sarcoplasmic reticulum Ca2+ ATPase by cyclopiazonic acid did not alter the cardiac responses to adenosine and this was independent of thyroid status. It is suggested that distinct modulation of the extra- and intracellular adenosine actions is present in eu- and hyperthyroid hearts. In the latter, a predominance of intracellular adenosine mechanisms can be proposed.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Journal of pharmacological sciences 91 : 4 (2003), p. 295-304. -
További szerzők:	Zsuga Judit (1973-) (neurológus, pszichoterapeuta, egészségügyi szakmanager) Cseppentő Ágnes (1953-) (orvos) Bajza Ágnes (1970-) (biológus) Varga Angelika (1977-) (biológus) Szabó Judit Zsuzsanna (farmakológus, klinikai laboratóriumi szakorvos) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos)
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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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