Az egyes fehérjesejt-integrinek élettani szerepének vizsgálata génhiányos (knockout) egerek segítségével = the physiological role of individual leukocyte integrins studies using genetificient (knockout) mice

A támogatott kutatások során a neutrofil granulociták működését vizsgáltuk genetikai, biokémiai és farmakológiai megközelítésekkel. Legfontosabb tudományos eredményeink alábbiak voltak: 1) A neutrofil granulociták integrinjei önmagukban nem képesek a sejtek teljes aktiválódását létrehozni (Jakus et al., J Immunol 2004; IF: 6.70) 2) A humán genom a korábban feltételezettnél lényegesen több ITAM-tartalmú molekulát kódol (Fodor et al., Immunol Lett 2006; IF: 2.14) 3) Az integrinek jelátvitele ITAM-függő mechanizmusokon keresztül jön létre (Mócsai et al., Nat Immunol 2006; IF: 27.60) 4) Egy új integrin-jelátviteli modell felállítása (Jakus et al., Trends Cell Biol 2007;IF: 12.43) 5) Egér neutrofilek immunkomplex-mediált aktiválódása az FcgammaRIII és az FcgammaRIV együttműködésével jön létre (Jakus et al., J Immunol 2008; IF: 6.29) Ezek az eredmények nagyban járulnak hozzá a neutrofilek működésének és az autoimmun gyulladásos folyamatok patomechanizmusának megértéséhez. | The sponsored research activity focused on the analysis of neutrophil functions by genetic, biochemical and pharmacological approaches. Our most important observations were the following: 1) Neutrophil integrins by themselves are not able to induce full activation of the cells (Jakus et al., J Immunol 2004; IF: 6.70) 2) The human genome contains significantly more ITAM-containing adapters than previousy thought (Fodor et al., Immunol Lett 2006; IF: 2.14) 3) Integrins utilize an ITAM-based signal transduction mechanism (Mócsai et al., Nat Immunol 2006; IF: 27.60) 4) Development of a new integrin signal transduction model (Jakus et al., Trends Cell Biol 2007;IF: 12.43) 5) Activation of murine neutrophils by immune complexes proceeds through a cooperative action of FcgammaRIII and FcgammaRIV (Jakus et al., J Immunol 2008; IF: 6.29) These results will strongly contribute to the understanding of neutrophil functions and the pathomechanism of autoimmune inflammatory diseases

Male gender predisposes to development of endotoxic shock in the rat

Objective: After intravenous (i.v.) injection of lipopolysaccharide (LPS) macrophages release nitric oxide (NO) due to the expression of the inducible NO synthase (iNOS). After LPS NO is abundantly produced also in the cardiovascular system and may contribute to the development of hypotension and shock. Since the immune response, the synthesis of NO and the regulation of blood pressure (BP) differ between males and females, in the present study the effect of LPS on BP, renal function, the plasma and urinary concentration of the metabolites of NO as well as the splenic and aortic expression of the iNOS gene were compared between male and female rats. Methods: BP and renal function were measured in anesthetized rats following the i.v. injection of LPS (E. coli, 4 mg/kg). The NOx and NOx (metabolites of NO=NOx) concentration was measured by the Griess reaction. The iNOS gene expression was studied by RT-PCR. Results: Four hours after LPS, BP of males (n=9) was reduced by 63+/-12 mmHg versus 10+/-4 in females (n=7, P<0.005). Aminoguanidine, a selective inhibitor of iNOS, prevented the reduction of BP in males. The plasma concentration of NOx (P-NOx, mu M) was lower in hypotensive males (128+/-20) than in normotensive females (235+/-29, P<0.005). Males also exhibited lower urinary NO, excretion (UNOxV) after LPS (P<0.001 vs, females). Prior castration of males provided protection against hypotension (fall of BP: -4+/-4 mmHg, n=6, P<0.02 versus males) and resulted in higher P-NOx as well as UNOxV (both P<0.001 versus males and not different from females). Prior ovariectomy (n=5) had no influence on the hemodynamic and NOx response to LPS. Male rats displayed enhanced aortic iNOS/beta-actin ratio relative to females after LPS (n=3 in each group, P<0.05). Conclusions: (1) Male gender may sensitize to LPS-induced shock and (2) sensitivity of males to endotoxin is associated with an attenuated, not exaggerated total rate of NO synthesis

Miért mennek/mentek külföldre a debreceni orvosok? Egy felmérés eredményei | Why would doctors from Debrecen go abroad? Results of a questionnaire

Absztrakt: Bevezetés: Számos hiedelem van az orvosok elvándorlásával kapcsolatban. A legfontosabb az, hogy szinte kizárólag az anyagiakról lenne szó. Számos kevésbé anyagi jellegű, így talán könnyebben megoldható tényező is szerepet játszhat az elvándorlásban. Módszer: Egy 37 kérdésből álló kérdőívet küldtünk ki a korábban Debrecenben végzett kollégáknak. Összesen 82-en küldtek vissza értékelhető kérdőívet. Eredmények: Kollégáink átlagosan 32 évesen távoztak. A legnépszerűbb célország az Egyesült Államok volt, de oda sokan mentek kutatni is. Európában a legnépszerűbb öt ország sorrendben: Svédország, Németország, Egyesült Királyság, Svájc és Norvégia volt. Felmérésünkben a legnépszerűbb öt szakma sorrendben: családorvos, belgyógyász, aneszteziológia/intenzív terápia, laboratóriumi orvos/patológus, sebész voltak. Ami a kinti munka tervezett időtartamát illeti, a kimenetelkor a kollégák körülbelül negyede egészen rövid távra (<2 év) tervezett. Amikor most megkérdeztük őket, jelentősen nőtt a hosszabb távot, sőt végleges kint maradást (most 38%) tervezők aránya. Amikor az eltávozás okait kutattuk, az életpálya/jövőkép hiánya volt a legfőbb ok. A fizetés, az életminőség, családi okok és a kalandvágy csak ezt követte. Az elégedettséget okozó (optimális) havi bért átlagosan 1,3 millió Ft-ra, a reális bért átlagosan 486 ezer Ft-ra becsülték. Következtetések: Bár a visszatérést a megkérdezettek jelentős része nem látja reálisnak, nem mondható el, hogy a fizetés lenne a legfőbb vagy az egyetlen oka az elvándorlásnak. Számos nem anyagi jellegű tényező áll az eltávozás és a „vissza nem térés” hátterében, amit pozitív hozzáállással relatíve könnyebben meg lehetne változtatni. Orv Hetil. 2017; 158(37): 1458–1468. | Abstract: Introduction: Numerous beliefs have arisen in relation to the emigration of doctors. First of all, in most cases emigration has been attributed to, almost exclusively, low salaries. There are a number of non-financial issues that could possibly be more easily addressed. Method: In order to get closer to these issues, we sent out a 37-item questionnaire to doctors, who originally graduated from the University of Debrecen. Altogether 82 of them sent back the questionnaire. Results: The mean age at the time of emigration was 32 years. The most popular destination was the United States, however, many colleagues left for the US to do research, as well as clinical practice. Among the European countries, the most popular ones were Sweden, Germany, United Kingdom, Switzerland and Norway. The five most popular clinical specialties were general practice, internal medicine, anesthesiology/intensive care, laboratory/pathology and surgery. With respect to the planned duration of working abroad, at the time of emigration one-fourth of our colleagues planned very short (<2 years) stay. When we asked them now, 38% plans much longer, even indefinite stay. The most common reasons of emigration were also assessed. The most common one was the lack of career track, followed by low salary, quality of life, family issues and adventurousness. Interestingly, burnout and “gratuities” were at the end of the list. A mean 1.3 million HUF per month would make our colleagues satisfied but they think that a mean 486.000 HUF would be realistic and would keep most doctors within the country. As far as university education is concerned, our colleagues agreed that the basic medical knowledge of Hungarian doctors is excellent, but their practical skills are much worse. Conclusions: Although returning to Hungary would be unrealistic by most colleagues, low salaries are definitely not the most important or exclusive reason for leaving the country. These issues are rather complex, there are numerous non-financial issues, which could be addressed much easier by expressing a positive attitude. Orv Hetil. 2017; 158(37): 1458–1468

Káosz elméleti kutatás véges számú teljesitmény kapcsolókat tartalmazó, nemlineáris. dinamikus, szabályozott rendszerekben = Research with Chaos Theory in Nonlinear, Dynamic, Feedback Controlled Systems Containing Finite Number of Power Switches

A kutatás négy témakörben folyt. Kaotikus tartományban működő nemlineáris villamos hajtás stabilis trajektóriára állítása témában a legfontosabb eredmény az volt, hogy a motor árammal arányos jelhez külső periodikus fűrészfog alakú jelet adva el lehetett érni a jel meredekségének megváltoztatásával, hogy a rendszerre ható külső jelek (terhelő nyomaték, tápfeszültség, fordulatszám alapjel) terének egy általunk megválasztott széles tartományában a rendszer stabilis maradjon, míg ugyanitt a fűrészfog alakú jel nélkül a rendszer kaotikus, labilis állapotba került. A megújuló energiák témában az ultranagy fordulatszámú gép szabályozásával, egy új kombinált napelem-termikus rendszer elméleti, szimulációs és kísérleti vizsgálatával és a mikrogridek feszültségszabályozásával foglalkoztunk. A pulzus szélesség modulációs eljárásokkal kapcsolatban egyes irodalmi állításokkal szemben bizonyítottuk, hogy jelentős egyenáramú komponens is felléphet. Francia, olasz és japán kooperációban végzett kutatás során a konverterek által generált harmonikusokat csökkentő két módszert dolgoztuk ki. Az eredményeket 45 cikkben publikáltuk. Egy kivételével valamennyi angol nyelvű és három kivételével valamennyi külföldön jelent meg Európa, Amerika, Ázsia és Afrika országaiban. | The research has had four topics. The most important result in the topic dealing with the connection to a stable orbit of a chaotic trajectory of nonlinear electrical drive operating in chaotic region was as follows: The system remain stable in wide range of the input signals (load torque, supply voltage, speed reference signal) selected by us provided that, the slope of an input periodical saw tooth signal added to the signal proportional to the motor current has been change. Otherwise the system remained operating in chaotic state without the application the saw tooth signal. In the renewable energy topic the control of ultra-high speed machine and the theoretical and simulation, test of the new combined solar-thermal system as well as voltage control of micro-grids were the research fields. Contrary to the statements found in the relevant literature dealing with the pulse width modulation it has been proved that considerable amount of DC-DC current can be generated. Two methods for suppressing harmonics generated by the electrical energy conversion have been developed in French, Italian, and Japanese cooperation. The research results have been published in 45 papers. All of them but one was written in English and they were published outside of Hungary in Europe, Asia, America, and Africa except three of them

Post-Ischemic Renal Fibrosis Progression Is Halted by Delayed Contralateral Nephrectomy : The Involvement of Macrophage Activation

(1) Background: Successful treatment of acute kidney injury (AKI)-induced chronic kidney disease (CKD) is unresolved. We aimed to characterize the time-course of changes after contralateral nephrectomy (Nx) in a model of unilateral ischemic AKI-induced CKD with good translational utility. (2) Methods: Severe (30 min) left renal ischemia-reperfusion injury (IRI) or sham operation (S) was performed in male Naval Medical Research Institute (NMRI) mice followed by Nx or S one week later. Expression of proinflammatory, oxidative stress, injury and fibrotic markers was evaluated by RT-qPCR. (3) Results: Upon Nx, the injured kidney hardly functioned for three days, but it gradually regained function until day 14 to 21, as demonstrated by the plasma urea. Functional recovery led to a drastic reduction in inflammatory infiltration by macrophages and by decreases in macrophage chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) mRNA and most injury markers. However, without Nx, a marked upregulation of proinflammatory (TNF-α, IL-6, MCP-1 and complement-3 (C3)); oxidative stress (nuclear factor erythroid 2-related factor 2, NRF2) and fibrosis (collagen-1a1 (Col1a1) and fibronectin-1 (FN1)) genes perpetuated, and the injured kidney became completely fibrotic. Contralateral Nx delayed the development of renal failure up to 20 weeks. (4) Conclusion: Our results suggest that macrophage activation is involved in postischemic renal fibrosis, and it is drastically suppressed by contralateral nephrectomy ameliorating progression

Perceived Autonomy Support and Motivation in Young People: A Comparative Investigation of Physical Education and Leisure-Time in Four Countries

Physical education focuses on the development of sports skills as well as fitness for health. In Central European countries there has been a shift in these focuses since the fall of Communism to follow internationally-recognised health-related physical activity recommendations, similar to Western European countries. In this study we investigated the extent to which motivation from school physical education transfers to leisure-time physical activity providing autonomy support by three social agents: school (physical education teachers), family and peers. Our study utilised the Aetological Approach (AA), Ecological Model (EM) and the Trans-Contextual Model (TCM) that consists of the Theory of Planned Behaviour (TPB) and the Self-Determination Theory (SDT) to explore how autonomous motivation is transferred between contexts (physical education, leisure-time and current behaviour). Nine-hundred and seventy-four students aged 11–18 (55% girls) participated in our study from four countries: Hungary, United Kingdom, Romania and Slovakia. A prospective research design was employed, and questionnaires were administered at three time points. Using 7-point Likert scales, attitude, usefulness, and affectiveness were measured. Furthermore, subjective norms and perceived behavioural control (PBC) were tested within TPB. Autonomous and controlling motivation were measured within SDT by administering the Behavioural Regulation in Exercise questionnaires (BREQ and BREQ-2). Finally, past physical activity, intention and current physical activity behaviours were tested. Results indicated that perceived autonomy support from family and friends predicted autonomous motivation towards leisure-time physical activity in all four countries. However, teachers’ behaviour in some Eastern European countries did not predict this transfer. In general, in line with previous literature, boys reported more physical activity than girls. A strong influencing factor in the path model was that past behaviour predicted current behaviour, and according to that factor, boys reported being more active than girls.Boys also perceived more support from PE teachers than girls which was likely to have influenced their autonomous motivation in PE, which in turn transferred to leisure time. We discuss these results in the context of theories exploring the role of motivation and social environment on children’s choices related to physical activity. In conclusion, we suggest providing more autonomy support, especially by schools, for the enhancement of autonomous motivation of young people to promote their leisure time physical activity

Effects of 1-year anti-TNF-α therapies on bone mineral density and bone biomarkers in rheumatoid arthritis and ankylosing spondylitis

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Effects of 1-year anti-TNF-α therapy on vascular function in rheumatoid arthritis and ankylosing spondylitis

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