Szoboravatás

INAUGURATION OF A STATUE OF DR. GYULA ELISCHER (1875–1939) IN THE SCULPTURE GARDEN OF DEBRECEN UNIVERSITY’S CAMPUS. he brief text highlights the inauguration, on November 8, 2014, of a bust of Gyula Elischer of hurzóbánya on the campus of the University of Debrecen. he text ofers a description of the life career of the world-famous radiologist professor, Hungary’s irst radiographer, his professional achievements and printed publications. he text also underscores the fact that Professor Elischer – like many other doctors of the heroic age of radiology – sacriiced his life in the service of science and of his fellow human beings

Vese ischemia/reperfúziós károsodásának gátlása RNS interferencia segítségével = RNA interference (RNAi) to limit kidney ischemia/reperfusion injury.

Az RNS interferencia a génterápia új, ígéretes területe. Korábbi kísérleteink során elsőként alkalmaztuk ezt az új technológiát a vese ischemia-reperfúzós károsodásának gátlására (Hamar: PNAS, 2004, US.Apps - 20080227733). Az intenzív osztályon bekövetkezett haláleset kb. 30%-a a vese oxigénhiányos károsodásának következménye. Az oxigénhiányos állapotban elszenvedett szövetkárosodást kiterjedésében, súlyosságában meghaladhatja a véráramlás újbóli megindulását követő reperfúziós károsodás. A reperfúziós során keletkező oxigén szabadgyökök következtében súlyos oxidatív stressz okoz károsodást, és a sejtek programozott sejthalál (apoptózis) útján pusztulnak el. Ezért kísérleteink célja a vese reperfúziós károsodásának csökkentése. A FAS apoptózis receptor termelődését gátoló kezelésünk javította a veseműködést és a túlélést. A szabadgyök-termelő enzim kaszkád első elemét a NADPH-oxidáz (NOX-2,4) enzim termelődését gátló siRNS sejtkultúrában és egér-modellen javította a túlélést, a vese-működést. Kísérleteink során továbbá vizsgáljuk, az siRNS bejuttatásának leghatékonyabb módját, és az esetleges mellékhatásokat is. Eredményeinket két közleményben foglaltuk össze. A célszervbe-sejtbe történő bejuttatás hatékonyságának növelésében, sejt-specifikus célzott bevitel kifejlesztésében segítségünkre van Judy Liebermannal (Harvard Medical School, Boston, USA) akivel együttműködésben fejlesztettük ki az RNS interferencia alkalmazását egér máj és vese betegségek kezelésére. | RNA interference is a new, promising field of gene-therapy. We were the first, to apply this technique to inhibit reperfusion injury of the kidney (Hamar: PNAS, 2004, US.Apps - 20080227733). Renal oxygen depletion is a leading cause of death at the Intensive Care Units (ICU). Reperfusion injury following reconstitution of blood supply may substantially exceed the damage due to oxygen deficiency (ischemic injury). Oxygen radicals, produced during reperfusion induce a severe oxidative stress, and cells are lost through programmed cell death (apoptosis). Thus, our aim is to reduce reperfusion injury of the kidney. Inhibition of FAS apoptosis receptor improved renal function and survival. Inhibition of NADPH-oxidase (NOX-2,4) - the first enzyme of the oxidative radical producing enzyme cascade improved renal function, and cell survival in cell culture and mouse model. We summarized our data in 2 publications. Furthermore, we investigate the most effective way of targeting the siRNA in the right cell, and possible side-effects of siRNA in collaboration with Judy Liebermann (Harvard Medical School, Boston, USA), with whom we have developed application of RNA interference in mice for renal and liver diseases

Magnesium-dependent atpase as a possibility for the investigation of deponating environmental loads in a hepatocyte model

Chemicals that load the environment can be chlorobenzenes with massive chemical stability. They induce a dose-dependent toxic effect in the cells of affected tissues, and because of their high frequency of occurrence in the food chain, they can be used as expositors in environmental exposure models. In this work, we wanted to investigate the magnesium-dependent ATPase activity of chlorobenzenes in hepatocytes

A fibrocyte model for monitoring environmental chemicals

Human activity affects all elements of the Earth's environment and the system of relationships between them. Chlorobenzenes created during chemicalization are capable of modulating the adaptation potential of biological organisms and because of their high frequency of occurrence in the food chain, they can be used as expositors in environmental exposure models. It is necessary to develop a biological model system suitable for the investigation of environmental pollutant chemical agents, which indicates changes quickly and easily

Multiple Binding Sites for Melatonin on Kv1.3

AbstractMelatonin is a small amino acid derivative hormone of the pineal gland. Melatonin quickly and reversibly blocked Kv1.3 channels, the predominant voltage-gated potassium channel in human T-lymphocytes, acting from the extracellular side. The block did not show state or voltage dependence and was associated with an increased inactivation rate of the current. A half-blocking concentration of 1.5mM was obtained from the reduction of the peak current. We explored several models to describe the stoichiometry of melatonin-Kv1.3 interaction considering one or four independent binding sites per channel. The model in which the occupancy of one of four binding sites by melatonin is sufficient to block the channels gives the best fit to the dose-response relationship, although all four binding sites can be occupied by the drug. The dissociation constant for the individual binding sites is 8.11mM. Parallel application of charybdotoxin and melatonin showed that both compounds can simultaneously bind to the channels, thereby localizing the melatonin binding site out of the pore region. However, binding of tetraethylammonium to its receptor decreases the melatonin affinity, and vice versa. Thus, the occupancy of the two separate receptor sites allosterically modulates each other

Urológiai elváltozások nőgyógyászati tumoros betegeknél

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Ductular reaction correlates with fibrogenesis but does not contribute to liver regeneration in experimental fibrosis models

BACKGROUND AND AIMS: Ductular reaction is a standard component of fibrotic liver tissue but its function is largely unknown. It is supposed to interact with the matrix producing myofibroblasts and compensate the declining regenerative capacity of hepatocytes. The relationship between the extent of fibrosis-ductular reaction, proliferative activity of hepatocytes and ductular reaction were studied sequentially in experimental hepatic fibrosis models. METHODS: Liver fibrosis/cirrhosis was induced in wild type and TGFbeta overproducing transgenic mice by carbon tetrachloride and thioacetamide administration. The effect of thioacetamide was modulated by treatment with imatinib and erlotinib. The extent of ductular reaction and fibrosis was measured by morphometry following cytokeratin 19 immunofluorescent labeling and Picro Sirius staining respectively. The proliferative activity of hepatocytes and ductular reaction was evaluated by BrdU incorporation. The temporal distribution of the parameters was followed and compared within and between different experimental groups. RESULTS: There was a strong significant correlation between the extent of fibrosis and ductular reaction in each experimental group. Although imatinib and erlotinib temporarily decreased fibrosis this effect later disappeared. We could not observe negative correlation between the proliferation of hepatocytes and ductular reaction in any of the investigated models. CONCLUSIONS: The stringent connection between ductular reaction and fibrosis, which cannot be influenced by any of our treatment regimens, suggests that there is a close mutual interaction between them instead of a unidirectional causal relationship. Our results confirm a close connection between DR and fibrogenesis. However, since the two parameters changed together we could not establish a causal relationship and were unable to reveal which was the primary event. The lack of inverse correlation between the proliferation of hepatocytes and ductular reaction questions that ductular reaction can compensate for the failing regenerative activity of hepatocytes. No evidences support the persistent antifibrotic property of imatinib or erlotinib

A juxtaglomeruláris apparátus parakrin szabélyozása: Funkcionális és morfológiai összefüggések normál és kóros körülmények között = Paracrine Control of the Juxtaglomerular Apparatus: Functional and Morphological Correlations in Health and Disease

Speciális technika kifejlesztésével és a két foton lézermikroszkóp segítségével elsőként tettük láthatóvá in vivo a patkány vese afferens arteriola disztális szakaszán található endotheliális fenesztrációt. Kimértük a fenesztrált terület nagyságát és bizonyítottuk annak életkortól, illetve a szervezet aktuális állapotától függő változását. Real time formában nyomon követtük a renin granulumok ezen keresztüli keringésbe jutását. Igazoltuk, hogy a filtráció már a glomerulust megelőző disztális afferens arteriola szakaszban megkezdődik. Vizualizáltuk a juxtaglomeruláris apparátus intersticiális folyadék mozgását és kimutattuk, hogy a juxtaglomeruláris apparátusba folyadék filtrálódik az afferens arteriolából, a mesangiumon keresztül a glomerulusból, illetve a glomerulusból a macula densan keresztül a disztális tubulusba. Ezek az eredmények alapvetően megkérdőjelezik a juxtaglomeruláris apparátus működésére és jelentőségére vonatkozó eddigi elképzeléseinket. A fenesztráció kialakulását, illetve a hozzátartozó nanocsatornák morfológiáját atomerőmikroszkópiával analizáltuk sejttenyészetben. Az angiotenzin II és a vaszkuláris endotheliális növekedési faktor (VEGF) fokozta a fenesztrumok képződését az AT1, illetve a VEGFR-2 receptoron keresztül. E folyamat függ a p38 aktiválódásától. A fenesztráció fokozódása együtt járt a 40kD-os dextran áteresztőképesség növekedésével és a sejtréteg elektromos impedancia csökkenésével. | With a special technical development and the use of two photon laser microscopy, for the first time, in vivo, we managed to visualize the endothelial fenestration at the distal section of the afferent arteriole in rat kidney. The area of the fenestrated section was measured and its change depending on age and actual condition was demonstrated. The passage of the renin granules into the circulation via these fenestrations were followed in real time. We documented that filtration already starts at the distal part of the afferent arteriole before glomerulus. The interstitial fluid movement in the juxtaglomerular apparatus was visualized. It was also shown that in JGA, fluid is filtered via afferent arteriole, mesangium, glomerulus and macula densa into the distal tubule. These findings basically question our understanding about the function and importance of JGA. The development of fenestration and the morphology of the related nanochannels were analyzed in the cell culture with the help of AFM. Angiotensin II and Vascular Endothelial Growth Factor (VEGF) increased fenestrates via AT1 and VEGFR-2 receptors. This process is p38 dependent. Increase in fenestration was accompanied by increase in permeability to 40kD dextran and decrease in cell layer electrical impedance