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001-es BibID:	BIBFORM077036
035-os BibID:	(WoS)000458934000210 (Scopus)85061291471
Első szerző:	Bombicz Mariann (gyógyszerész)
Cím:	The Drug Candidate BGP-15 Delays the Onset of Diastolic Dysfunction in the Goto-Kakizaki Rat Model of Diabetic Cardiomyopathy / Bombicz Mariann, Priksz Daniel, Gesztelyi Rudolf, Kiss Rita, Hollos Nora, Varga Balazs, Nemeth Jozsef, Toth Attila, Papp Zoltan, Szilvassy Zoltan, Juhasz Bela
Dátum:	2019
ISSN:	1420-3049
Megjegyzések:	Background and Aims: Diabetic cardiomyopathy (DCM) is an emerging problem worldwide due to an increase in the incidence of type 2 diabetes. Animal studies have indicated that metformin and pioglitazone can prevent DCM partly by normalizing insulin resistance, and partly by other, pleiotropic mechanisms. One clinical study has evidenced the insulin-senzitizing effect of the drug candidate BGP-15, along with additional animal studies that have confirmed its beneficial effects in models of diabetes, muscular dystrophy and heart failure, with the drug affecting chaperones, contractile proteins and mitochondria. Our aim was to investigate whether the inzulin-senzitizer BGP-15 exert any additive cardiovascular effects compared to metformin or pioglitazone, using Goto-Kakizaki (GotoK) rats. Methods: Rats were divided into five groups: (I) healthy control (Wistar), (II) diseased (GotoK), and GotoK rats treated with: (III) BGP-15, (IV) metformin, and (V) pioglitazone, respectively, for 12 weeks. Metabolic parameters and insulin levels were determined at the endpoint. Doppler echocardiography was carried out to estimate diabetes-associated cardiac dysfunction. Thoracotomy was performed after the vascular status of rats was evaluated using an isolated aortic ring method. Furthermore, western blot assays were carried out to determine expression or phosphorylation levels of selected proteins that take part in myocyte relaxation. Results: BGP-15 restored diastolic parameters (e·/a·, E/e·, LAP, E and A wave) and improved Tei-index compared to untreated GotoK rats. Vascular status was unaffected by BGP-15. Expression of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) and phosphodiesterase 9A (PDE9A) were unchanged by the treatments, but the phosphorylation level of vasodilator-stimulated phosphoprotein (VASP) and phospholamban (PLB) increased in BGP-15-treated rats, in comparison to GotoK. Conclusions: Even though the BGP-15-treatment did not interfere significantly with glucose homeostasis and vascular status, it considerably enhanced diastolic function, by affecting the SERCA/phospholamban pathway in GotoK rats. Although it requires further investigation, BGP-15 may offer a new therapeutic approach in DCM.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk BGP-15 diastolic dysfunction type 2 diabetes Goto-Kakizaki echocardiography
Megjelenés:	Molecules. - 24 : 3 (2019), p. 1-18. -
További szerzők:	Priksz Dániel (1989-) (farmakológus) Gesztelyi Rudolf (1969-) (kísérletes farmakológus) Kiss Rita (1974-) (laboratóriumi diagnosztika szakorvos) Hollós Nóra (1995-) (hallgató) Varga Balázs (1984-) (kísérletes farmakológus) Németh József (1954-) (vegyész, analitikus) Tóth Attila (1971-) (biológus) Papp Zoltán (1965-) (kardiológus, élettanász) Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus) Juhász Béla (1978-) (kísérletes farmakológus)
Pályázati támogatás:	GINOP-2.3.4-15-2016-00002 GINOP
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001-es BibID:	BIBFORM072627
035-os BibID:	(cikkazonosító)771 (scopus)85043576366 (wos)000428309800128
Első szerző:	Kiss Rita (laboratóriumi diagnosztika szakorvos)
Cím:	Insulin-Sensitizer Effects of Fenugreek Seeds in Parallel with Changes in Plasma MCH Levels in Healthy Volunteers / Kiss Rita, Szabó Katalin, Gesztelyi Rudolf, Somodi Sándor, Kovács Péter, Szabó Zoltán, Németh József, Priksz Dániel, Kurucz Andrea, Juhász Béla, Szilvássy Zoltán
Dátum:	2018
ISSN:	1661-6596 1422-0067
Megjegyzések:	In developed, developing and low-income countries alike, type 2 diabetes mellitus (T2DM)is one of the most common chronic diseases, the severity of which is substantially a consequenceof multiple organ complications that occur due to long-term progression of the disease beforediagnosis and treatment. Despite enormous investment into the characterization of the disease, itslong-term management remains problematic, with those afflicted enduring significant degradationin quality-of-life. Current research efforts into the etiology and pathogenesis of T2DM, are focusedon defining aberrations in cellular physiology that result in development of insulin resistance andstrategies for increasing insulin sensitivity, along with downstream effects on T2DM pathogenesis.Ongoing use of plant-derived naturally occurring materials to delay the onset of the disease oralleviate symptoms is viewed by clinicians as particularly desirable due to well-established efficacyand minimal toxicity of such preparations, along with generally lower per-patient costs, in comparisonto many modern pharmaceuticals. A particularly attractive candidate in this respect, is fenugreek,a plant that has been used as a flavouring in human diet through recorded history. The presentstudy assessed the insulin-sensitizing effect of fenugreek seeds in a cohort of human volunteers, andtested a hypothesis that melanin-concentrating hormone (MCH) acts as a critical determinant ofthis effect. A test of the hypothesis was undertaken using a hyperinsulinemic euglycemic glucoseclamp approach to assess insulin sensitivity in response to oral administration of a fenugreek seedpreparation to healthy subjects. Outcomes of these evaluations demonstrated significant improvementin glucose tolerance, especially in patients with impaired glucose responses. Outcome data furthersuggested that fenugreek seed intake-mediated improvement in insulin sensitivity correlated withreduction in MCH levels.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk hyperinsulinemic euglycemic glucose clamp (HEGC) fenugreek melanin-concentrating hormone (MCH) RIA type 2 diabetes clinical pilot study
Megjelenés:	International Journal Of Molecular Sciences. - 19 : 3 (2018), p. 1-17. -
További szerzők:	Szabó Katalin (1989-) (táplálkozástudományi szakember) Gesztelyi Rudolf (1969-) (kísérletes farmakológus) Somodi Sándor (1977-) (belgyógyász) Kovács Péter (1947-) (belgyógyász, kardiológus, klinikai farmakológus) Szabó Zoltán (1973-) (belgyógyász, kardiológus) Németh József (1954-) (vegyész, analitikus) Priksz Dániel (1989-) (farmakológus) Kurucz Andrea (1984-) (orvos) Juhász Béla (1978-) (kísérletes farmakológus) Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus)
Pályázati támogatás:	GINOP-2.3.4-15-2016-00002 GINOP AGR-PIAC-13-1-2013-0008 Egyéb
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001-es BibID:	BIBFORM085888
035-os BibID:	(cikkazonosító)2124 (scopus)85082286798 (wos)000529890200220
Első szerző:	Wachal Zita
Cím:	Retinoprotection by BGP-15, a Hydroximic Acid Derivative, in a Type II Diabetic Rat Model Compared to Glibenclamide, Metformin, and Pioglitazone / Wachal Zita, Bombicz Mariann, Priksz Dániel, Hegedűs Csaba, Kovács Diána, Szabó Adrienn Mónika, Kiss Rita, Németh József, Juhász Béla, Szilvássy Zoltán, Varga Balázs
Dátum:	2020
ISSN:	1661-6596 1422-0067
Megjegyzések:	High blood glucose and the consequential ischemia-reperfusion (I/R) injury damage vessels of the retina, deteriorating its function, which can be clearly visualized by electroretinography (ERG). The aim of the present study was to evaluate the possible retinoprotective effects of systemic BGP-15, an emerging drug candidate, in an insulin resistant animal model, the Goto-Kakizaki rat, and compare these results with well-known anti-diabetics such as glibenclamide, metformin, and pioglitazone, which even led to some novel conclusions about these well-known agents. Experiments were carried out on diseased animal model (Goto-Kakizaki rats). The used methods include weight measurement, glucose-related measurements?like fasting blood sugar analysis, oral glucose tolerance test, hyperinsulinemic euglycemic glucose clamp (HEGC), and calculations of different indices from HEGC results?electroretinography and Western Blot. Beside its apparent insulin sensitization, BGP-15 was also able to counteract the retina-damaging effect of Type II diabetes comparable to the aforementioned anti-diabetics. The mechanism of retinoprotective action may include sirtuin 1 (SIRT1) and matrix metalloproteinase 9 (MMP9) enzymes, as BGP-15 was able to elevate SIRT1 and decrease MMP9 expression in the eye. Based on our results, this emerging hydroximic acid derivative might be a future target of pharmacological developments as a potential drug against the harmful consequences of diabetes, such as diabetic retinopathy.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk electroretinography (ERG) Goto-Kakizaki rat pioglitazone metformin glibenclamide BGP diabetic retinopathy
Megjelenés:	International Journal Of Molecular Sciences. - 21 : 6 (2020), p. 1-19. -
További szerzők:	Bombicz Mariann (1987-) (gyógyszerész) Priksz Dániel (1989-) (farmakológus) Hegedűs Csaba (1983-) (Molekuláris biológus, Cera-Med Kft. Debrecen) Kovács Diána Klára (1985-) (Molekuláris biológus) Szabó Adrienn Mónika (1982-) (orvos) Kiss Rita (1974-) (laboratóriumi diagnosztika szakorvos) Németh József (1954-) (vegyész, analitikus) Juhász Béla (1978-) (kísérletes farmakológus) Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus) Varga Balázs (1984-) (kísérletes farmakológus)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00043 GINOP EFOP-3.6.3-VEKOP-16-2017-00009 EFOP NKFIH-1150-6/2019 NKFIH
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