Az elhízás és cukorbetegség kezelésére alkalmas új molekuláris targetek meghatározása és validálása = Identification and validation of novel molecular target for obesity and type 2 diabetes

A kutatási tervben megfogalmazott programunk elsődleges célja az volt, hogy korunk népbetegségének számító elhízás, metabolikus szindróma és 2-es típusú cukorbetegség kialakulásában szerepet játszó élettani és kórélettani mechanizmusokat feltárjuk, továbbá gyógyszerfejlesztési célpontokat azonosítsunk ezen betegségek megelőzésére és kezelésére. A program másodlagos célja, a cukorbetegek körében nagyon gyakori halálok, a szív és érrendszeri betegségek, elsősorban a szívritmuszavarok kialakulásának hátterében álló mechanizmusok tisztázása volt. Munkánk során különböző állatkísérletes modellekben, patkányokon és nyulakon vizsgáltuk: a CCK szerepét az atípusos antipsychoticumok szedése okozta súlygyarapodásra; a hyperinsulinaemia hatását a cardialis elektrofiziológiai paraméterekre. Új DPP-IV gátló vegyületeket terveztünk és szintetizáltunk, majd meghatároztuk hatásosságuk mértékét. Egy klinikai tanulmányban egészséges önkénteseken vizsgáltuk az egyszeri dózisban adott olanzapinnak (atípusos antipsychoticum), az étkezés kiváltotta CCK felszabadulásra gyakorolt hatását. Intézetünk izotóp laboratóriumában új radioimmunoassay (RIA) eljárásokat fejlesztettünk ki az OTKA támogatás segítségével a GLP-1, GIP, oxyntomodulin, thrittene és a corticosterone mérésére. | 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 a multivitamin preparation supplemented with phytosterol on serum lipids and infarct size in rats fed with normal and high cholesterol diet

BACKGROUND: Although complex multivitamin products are widely used as dietary supplements to maintain health or as special medical food in certain diseases, the effects of these products were not investigated in hyperlipidemia which is a major risk factor for cardiovascular diseases. Therefore, here we investigated if a preparation developed for human use containing different vitamins, minerals and trace elements enriched with phytosterol (VMTP) affects the severity of experimental hyperlipidemia as well as myocardial ischemia/reperfusion injury. METHODS: Male Wistar rats were fed a normal or cholesterol-enriched (2% cholesterol + 0.25% cholate) diet for 12 weeks to induce hyperlipidemia. From week 8, rats in both groups were fed with a VMTP preparation or placebo for 4 weeks. Serum triglyceride and cholesterol levels were measured at week 0, 8 and 12. At week 12, hearts were isolated, perfused according to Langendorff and subjected to a 30-min coronary occlusion followed by 120 min reperfusion to measure infarct size. RESULTS: At week 8, cholesterol-fed rats showed significantly higher serum cholesterol level as compared to normal animals, however, serum triglyceride level did not change. VMTP treatment significantly decreased serum cholesterol level in the hyperlipidemic group by week 12 without affecting triglyceride levels. However, VMTP did not show beneficial effect on infarct size. The inflammatory marker hs-CRP and the antioxidant uric acid were also not significantly different. CONCLUSIONS: This is the first demonstration that treatment of hyperlipidemic subjects with a VMTP preparation reduces serum cholesterol, the major risk factor for cardiovascular disease; however, it does not provide cardioprotection

Signs of in-situ geochemical interactions at the granite–concrete interface of a radioactive waste disposal

Abstract Eleven unique core samples from the National Radioactive Waste Repository of Hungary, Bátaapáti were studied in this work. The samples all cross the granite–concrete interface and have been drilled from around 275 m depth from the surface, 1–15 months after concrete injection. Phase analytical techniques, optical microscopy, SEM-EDS and Raman-spectroscopy were used for the analysis of interactions between granitic rock and cementitious building material. Newly formed phases, Ca-carbonates and titanite, were observed at the interface. Carbonation may reduce the porosity and permeability in the contact zone. The presence of titanite indicates the changing geochemical and thermodynamical constrains along the reaction front of granite–concrete, furthermore, it may help in the validation of future geochemical models. The cementitious material is seen to penetrate among the sheets of biotite mineral in granite which process is probable to cause the attachment of granite and concrete

Multi-round recycling of green waste for the production of iron nanoparticles: synthesis, characterization, and prospects in remediation

Due to the widespread applications of metal nanoparticles (NPs), green synthesis strategies have recently advanced, e.g., methods that utilize extracts made from different plant wastes. A particularly innovative approach to reducing large amounts of available household/agricultural green wastes is their application in nanoparticle generation. Regarding this, the aim of our work was to examine the possibility of upgrading green nanoparticle syntheses from an innovative economic and environmental point of view, namely by investigating the multiple recyclabilities of green tea (GT), coffee arabica (CA), and Virginia creeper ( Parthenocissus quinquefolia ) (VC) waste residues for iron nanoparticle (FeNPs) synthesis. The plant extracts obtained by each extraction round were analyzed individually to determine the amount of main components anticipated to be involved in NPs synthesis. The synthesized FeNPs were characterized by X-ray powder diffraction and transmission electron microscopy. The activity of the generated FeNPs in degrading chlorinated volatile organic compounds (VOC) and thus their future applicability for remediation purposes were also assessed. We have found that VC and especially GT residues could be reutilized in multiple extraction rounds; however, only the first extract of CA was suitable for FeNPs’ generation. All of the obtained FeNPs could degrade VOC with efficiencies GT1-Fe 91.0%, GT2-Fe 83.2%, GT3-Fe 68.5%; CA1-Fe 76.2%; VC1-Fe 88.2%, VC2-Fe 79.7%, respectively, where the number (as in GT3) marked the extraction round. These results indicate that the adequately selected green waste material can be reutilized in multiple rounds for nanoparticle synthesis, thus offering a clean, sustainable, straightforward alternative to chemical methods

Preparation of TiO2–MoO3 composite nanofibers by water-based electrospinning process and their application in photocatalysis

Coupling TiO2 nanofibers with other semiconductor metal oxides can effectively extend the light absorbability of TiO2 to the visible range of the electromagnetic spectrum. This study demonstrates the synthesis of TiO2–MoO3 composite nanofibers via electrospinning using Ti and Mo water-soluble precursors. Aqueous solutions of these precursors were added to a PVP solution in N–N dimethylformamide. The mixture was electrospun, followed by annealing in air at 600 °C obtaining oxide nanofibers. The fibers were characterized via thermogravimetry and differential thermal analysis, X-ray photoelectron spectroscopy, scanning electron microscopy and energy-dispersive X-ray spectroscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy. The diameter of the TiO2–MoO3 fibers was between 90 and 110 nm after annealing, Furthermore, methylene blue dye was used to investigate the photocatalytic activity of the fibers in visible light. TiO2–MoO3 fibers showed the best photocalaytic activity with a rate constant of 0.0018 min−1 while pure TiO2 and MoO3 nanofibers had 0.0009 min−1 and 0.0008 min−1 respectively

Interplay of myosin phosphatase and protein phosphatase-2A in the regulation of endothelial nitric-oxide synthase phosphorylation and nitric oxide production

L