33 research outputs found
Impairment of nitrergic relaxation of the sphincter of Oddi in the state of tolerance to nitroglycerine, in experimental hypercholesterolaemia and lovastatin-treatment in rabbits
Role of sensory neurons on pancreatic beta cell function and on development of insulin resistance
Interplay between nitric oxide and VIP in CCK-8-induced phasic contractile activity in the rabbit sphincter of Oddi
Az elhĂzás Ă©s cukorbetegsĂ©g kezelĂ©sĂ©re alkalmas Ăşj molekuláris targetek meghatározása Ă©s validálása = Identification and validation of novel molecular target for obesity and type 2 diabetes
A kutatási tervben megfogalmazott programunk elsĹ‘dleges cĂ©lja az volt, hogy korunk nĂ©pbetegsĂ©gĂ©nek számĂtĂł elhĂzás, metabolikus szindrĂłma Ă©s 2-es tĂpusĂş cukorbetegsĂ©g kialakulásában szerepet játszĂł Ă©lettani Ă©s kĂłrĂ©lettani mechanizmusokat feltárjuk, továbbá gyĂłgyszerfejlesztĂ©si cĂ©lpontokat azonosĂtsunk ezen betegsĂ©gek megelĹ‘zĂ©sĂ©re Ă©s kezelĂ©sĂ©re. A program másodlagos cĂ©lja, a cukorbetegek körĂ©ben nagyon gyakori halálok, a szĂv Ă©s Ă©rrendszeri betegsĂ©gek, elsĹ‘sorban a szĂvritmuszavarok kialakulásának hátterĂ©ben állĂł mechanizmusok tisztázása volt. Munkánk során kĂĽlönbözĹ‘ állatkĂsĂ©rletes modellekben, patkányokon Ă©s nyulakon vizsgáltuk: a CCK szerepĂ©t az atĂpusos antipsychoticumok szedĂ©se okozta sĂşlygyarapodásra; a hyperinsulinaemia hatását a cardialis elektrofiziolĂłgiai paramĂ©terekre. Ăšj DPP-IV gátlĂł vegyĂĽleteket terveztĂĽnk Ă©s szintetizáltunk, majd meghatároztuk hatásosságuk mĂ©rtĂ©kĂ©t. Egy klinikai tanulmányban egĂ©szsĂ©ges önkĂ©nteseken vizsgáltuk az egyszeri dĂłzisban adott olanzapinnak (atĂpusos antipsychoticum), az Ă©tkezĂ©s kiváltotta CCK felszabadulásra gyakorolt hatását. IntĂ©zetĂĽnk izotĂłp laboratĂłriumában Ăşj radioimmunoassay (RIA) eljárásokat fejlesztettĂĽnk ki az OTKA támogatás segĂtsĂ©gĂ©vel a GLP-1, GIP, oxyntomodulin, thrittene Ă©s a corticosterone mĂ©rĂ©sĂ©re. | The primary objective of our proposed project was to explore the physiological and pharmacological basis of the development of obesity, insulin resistance and type-2 diabetes. The secondary objective of our research program was the investigation of the pathophysiological basis of the cardiac complication of the insulin resistance and diabetes. In this program: the role of CCK in the atypical antipsychotic-induced weight gain; the effect of hyperinsulinaemia on the cardiac electrophysiological parameters were investigated in different animal models using rats and rabbits. New chemical entities having DPP-IV blocking activity were designed and synthetized and their potencies were determined. In a clinical trial we investigated the possible role of a single dose of olanzapine, an atypical antipsychotic, on the meal-induced CCK release in healthy volunteers. Furthermore, new radioimmunoassay (RIA) methods were developed in our institute for the measurement of GLP-1, GIP, oxyntomodulin, thrittene and corticosterone with the support of OTKA
Effect of melatonin on the severity of l-arginine-induced experimental acute pancreatitis in rats
AIM: To determine the effect of melatonin pre- and post-treatment on the severity
of L-arginine (L-Arg) -induced experimental pancreatitis in rats. METHODS: Male
Wistar rats (25) were divided into five groups. Those in group A received two
injections of 3.2g/kg body weight L-Arg i.p. at an interval of 1h. In group MA,
the rats were treated with 50 mg/kg body weight melatonin i.p. 30 min prior to
L-Arg administration. In group AM, the rats received the same dose of melatonin
1h after L-Arg was given. In group M, a single dose of melatonin was administered
as described previously. In group C the control animals received physiological
saline injections i.p. All rats were exsanguinated 24 h after the second L-Arg
injection. RESULTS: L-Arg administration caused severe necrotizing pancreatitis
confirmed by the significant elevations in the serum amylase level, the
pancreatic weight/body weight ratio (pw/bw), the pancreatic IL-6 content and the
myeloperoxidase activity, relative to the control values. Elevation of the serum
amylase level was significantly reduced in rats given melatonin following L-Arg
compared to rats injected with L-Arg only. The activities of the pancreatic
antioxidant enzymes (Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase (CAT))
were significantly increased 24 h after pancreatitis induction. Melatonin given
in advance of L-Arg significantly reduced the pancreatic CAT activity relative to
that in the rats treated with L-Arg alone. In the liver, L-Arg significantly
increased the lipid peroxidation level, and the glutathione peroxidase and
Cu/Zn-SOD activities, whereas the Mn-SOD activity was reduced as compared to the
control rats. Melatonin pre-treatment prevented these changes. CONCLUSION:
Melatonin is an antioxidant that is able to counteract some of the L-Arg-induced
changes during acute pancreatitis, and may therefore be helpful in the supportive
therapy of patients with acute necrotizing pancreatitis
A hiperkoleszterinemiához Ă©s az inzulin rezisztenciához társult iszkĂ©miás szĂvbetegsĂ©g kezelĂ©sĂ©nek Ăşj farmakoterápiás stratĂ©giái. EndogĂ©n kardioprotektĂv mechanizmusok farmakolĂłgiai kihasználása = Novel pharmacotherapeutic strategies of ishaemic heart disease associated with hypercholesterolaemia and insulin resistance. Pharmacological exploitation of endogenous cardioproctective mechanisms
A kutatás során fĂ©ny derĂĽlt arra, hogy az insulin rezisztenciához társult iszkĂ©miás szĂvbetegsĂ©g farmakoterápiája során egy Ăşjonnan felismert endogĂ©n insulin Ă©rzĂ©kenyĂtĹ‘ mechanizmus, a HISS (hepatic insulin sensitizing substance) mechanizmus igen fontos lehet. FelderĂtettĂĽk, hogy ez a mechanizmus NO donorokkal Ă©s ciklikus GMP foszfodiĂ©szteráz gátlĂłkkal a terápia számára kiaknázhatĂł. BizonyĂtottuk azt is, hogy az emlĂtett gyĂłgyszercsoportok kĂĽlönbözĹ‘ tagjai alacsonyabb dĂłzisban kĂ©pesek insulin Ă©rzĂ©kenyĂtĹ‘ hatást elĂ©rni, mint ''klasszikus'' indikáciĂłikban (hypertonia, congestĂv szĂvelĂ©gtelensĂ©g, iszkĂ©miás szĂvbetegsĂ©g. Az eredmĂ©nyek alapján gyĂłgyszerfejlesztĂ©si folyamatok indultak meg. | The resuts achieved revealed the potential of a novel endogenous insulin sensitizing mechanism, the HISS process: hepatic insulin sensitizing substance mechanism) in treatment and prevention of cardiovascular disease underpinned by the insulin resistance syndrome. Our findings provided evidence for the use of cyclic GMP phosphodiesterase inhibitors and nitric oxide donors as tools for pharmacological exploitation of this mechanism. Moreover, it has also benn shown that drugs in these groups acieve insulin sensitization at doses much lower than those necessary to produce effects in theis ''classical'' indications such as sustained arterial hypertension, congestive heart failure and ischaemic heart disease. The resulds obtained promoted two drug development pharmaceutical projects