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001-es BibID:	BIBFORM107283
035-os BibID:	(WOS)000578238700017 (Scopus)85075798185
Első szerző:	Tóth Emese (molekuláris biológus)
Cím:	Novel mitochondrial transition pore inhibitor N-methyl-4-isoleucine cyclosporin is a new therapeutic option in acute pancreatitis / Emese Tóth, József Maléth, Noémi Závogyán, Júlia Fanczal, Anna Grassalkovich, Réka Erdős, Petra Pallagi, Gergő Horváth, Laszló Tretter, Emese Réka Bálint, Zoltán Rakonczay Jr., Viktória Venglovecz, Péter Hegyi
Dátum:	2019
ISSN:	0022-3751 1469-7793
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Journal Of Physiology-London. - 597 : 24 (2019), p. 5879-5898. -
További szerzők:	Maléth József Závogyán Noémi Fanczal Júlia Grassalkovich Anna Erdős Réka Pallagi Petra Horváth Gergő Tretter László Bálint Emese Réka Rakonczay Zoltán Venglovecz Viktória Hegyi Péter Jenő (belgyógyász)
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001-es BibID:	BIBFORM127848
035-os BibID:	(Scopus)85206849180 (WoS)001333699700001
Első szerző:	Venglovecz Viktória
Cím:	Restoring CFTR function with Orkambi decreases the severity of alcohol-induced acute pancreatitis / Viktória Venglovecz, Anna Grassalkovich, Emese Tóth, Attila Ébert, Eleonóra Gál, Marietta Margaréta Korsós, József Maléth, Zoltán Rakonczay, Zsolt Galla, Péter Monostori, Péter Hegyi
Dátum:	2024
ISSN:	0022-3751 1469-7793
Megjegyzések:	Abstract: Heavy alcohol intake is one of the most common causes of acute pancreatitis (AP). We have previously shown that ethanol (EtOH) decreases the expression and activity of the cystic fibrosis transmembrane conductance regulator (CFTR), which plays a key role in alcohol-induced AP development. The prescription drug, Orkambi (a combination of ivacaftor and lumacaftor) can correct impaired CFTR function and expression in cystic fibrosis (CF) patients. Thus, the present study aimed to investigate whether Orkambi can mitigate alcohol-induced AP. Intact guinea-pig pancreatic ducts were pre-treated with different concentrations of ethanol (EtOH; 30, 50 and 100 mm) for 12 h alone or in combination with ivacaftor (VX770) and/or lumacaftor (VX-809), and CFTR expression and activity were evaluated by immunostaining and by the patch clamp technique, respectively. Alcoholic AP was induced in Orkambi-treated guinea-pigs, and standard laboratory and histological parameters were measured. Ivacaftor and lumacaftor alone or in combination dose-dependently restored the apical expression and activity of CFTR after EtOH treatment in vitro. Oral administration of Orkambi reduced the severity of alcohol-induced AP and restored impaired CFTR activity and expression. Orkambi is able to restore the CFTR defect caused by EtOH and decreases the severity of alcohol-induced pancreatitis. This is the first in vivo pre-clinical evidence of Orkambi efficacy in the treatment of alcohol-induced AP. (Figure presented.). Key points: Acute pancreatitis is one of the leading causes of hospital admission among gastrointestinal diseases in which the lack of a specific drug therapy plays a crucial role. The cystic fibrosis transmembrane conductance regulator (CFTR) plays an essential role in pancreatic ductal HCO3-secretion; inappropriate CFTR function, as seen in heavy alcohol consumption, increases the risk of pancreatitis development. CFTR modulators are able to prevent the inhibitory effect of ethanol and reduce pancreatic ductal injury and the severity of alcohol-induced pancreatitis. CFTR modulators present a novel option in the pharmacotherapy of alcohol-induced pancreatitis by enhancing pancreatic functions or preventing recurrence.
Tárgyszavak:	Orvostudományok Egészségtudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk CFTR ethanol Orkambi pancreatitis
Megjelenés:	Journal Of Physiology-London. - 602 : 22 (2024), p. 6153-6170. -
További szerzők:	Grassalkovich Anna Tóth Emese (1990-) (molekuláris biológus) Ébert Attila Gál Eleonóra Korsós Marietta Margaréta Maléth József Rakonczay Zoltán Galla Zsolt Monostori Péter Hegyi Péter
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