101 results on '"Szanto I"'
Search Results
2. Hormonal Effects on the Expression of Na+/K+-ATPase Beta Subunit During Pregnancy
- Author
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Turi, A., Mullner, N., Szanto, I., Marcsek, Z., Bamberg, Ernst, editor, and Schoner, Wilhelm, editor
- Published
- 1994
- Full Text
- View/download PDF
3. TOPOLOGICAL DESCRIPTION OF A NON-DIFFERENTIABLE BIOECONOMICS MODEL
- Author
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GONZÁLEZ-OLIVARES, E., SÁEZ, E., STANGE, E., and SZÁNTÓ, I.
- Published
- 2005
4. A CUBIC SYSTEM WITH AN INVARIANT TRIANGLE SURROUNDING AT LEAST ONE LIMIT CYCLE
- Author
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Liu, Zhenhai, Sáez, E., and Szántó, I.
- Published
- 2003
5. The NADPH oxidase NOX5 protects against apoptosis in ALK-positive anaplastic large-cell lymphoma cell lines
- Author
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Carnesecchi, S., Rougemont, L. A., Doroshow, J. H., Nagy, M., Mouche, S., Gumy-Pause, F., and Szanto, I.
- Published
- 2015
- Full Text
- View/download PDF
6. Limit cycles and invariant parabola in a kukles system of degree three
- Author
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Zhenhai, Liu, Sáez, E., and Szántó, I.
- Published
- 2008
- Full Text
- View/download PDF
7. Limit cycles in Kukles systems of arbitrary degree with invariant ellipse
- Author
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Chavarriga, J., García, I.A., Sáez, E., and Szántó, I.
- Published
- 2007
- Full Text
- View/download PDF
8. Deficiency in the NADPH oxidase 4 predisposes towards diet-induced obesity
- Author
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Li, Y, Mouche, S, Sajic, T, Veyrat-Durebex, C, Supale, R, Pierroz, D, Ferrari, S, Negro, F, Hasler, U, Feraille, E, Moll, S, Meda, P, Deffert, C, Montet, Krause, K-H, and Szanto, I
- Published
- 2012
- Full Text
- View/download PDF
9. Insulinemia and leptinemia or of undernutrition in geriatric patients: markers of the metabolic syndrome or of undernutrition?
- Author
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Bonin-Guillaume, S, Herrmann, FR, Boillat, D, Szanto, I, Michel, JP, Rohner-Jeanrenaud, F, and Vischer, UM
- Published
- 2006
- Full Text
- View/download PDF
10. Linagliptin Effects on Heart Failure and Related Outcomes in Individuals With Type 2 Diabetes Mellitus at High Cardiovascular and Renal Risk in CARMELINA
- Author
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McGuire D, Alexander J, Johansen O, Perkovic V, Rosenstock J, Cooper M, Wanner C, Kahn S, Toto R, Zinman B, Baanstra D, Pfarr E, Schnaidt S, Meinicke T, George J, von Eynatten M, Marx N, Aizenberg D, Fiorella A, Edgardo N, Belen C, Alonso P, Walter M, Maia K, Guillermo S, Leandro B, Constanza R, Alejandra N, Melina C, Ariel I, Rodrigo C, Alvarez C, Jorge M, Gabriel C, German S, Bartolacci I, Bolobanich G, Tale T, Meritano M, Echeverria M, Gerrini S, Alvarez M, Torrijos N, Berli M, Coggiola J, Castaneda G, Rode R, Milessi R, Roude A, Bono J, Caresani J, Arias V, Westberg J, Allende G, Liberman A, Bordonava A, Almagro S, Gerbaudo C, Schiavi L, Budassi N, Cecilia M, Buncuga M, Carlos S, Osvaldo T, Mercedes S, Calella P, Agustina V, Aljandro M, Alberto D, Fiorella M, Cantero M, Cariganano M, Anadon P, Cartasegna L, Gabriela M, Fernanda A, Alberto R, Chacon C, Jazmin F, Colombo H, Coni E, Mattausch S, Thomsenhall K, della Torre M, Morandini M, Berra F, Margarita H, Commendatore V, Tedesco J, Bolzan P, Cuneo C, Narcisa G, Caputi V, Pablo S, Sandra G, Pacora F, Tinari M, Jure H, Parody M, Toranzo A, Frechtel G, Yohena S, Lovecchio S, Muller C, Martin S, Olivera C, Breyaui M, Bianchi G, Garcia C, Luciana V, Florencia F, Ruben G, Gelersztein E, Rey G, Sanchez C, Fornasari L, Di Pierro L, Giacomi G, Miguel S, Laura T, Gonzalo C, Ramon C, Glenny J, Koretzky M, Porto A, Tiberio O, Ellenberg A, Saurral R, Igarzabal C, Vilamajo O, Matkovich J, de Lapertosa S, Villagra M, Cuzziol G, de la Cruz M, Pinchetti R, Mierez M, Lopez C, Gorosito V, Gabito A, Kleiban A, Grosembacher L, Adrian P, Paula R, Javier G, Kraft F, Andres F, Krynski F, Nicolas P, Marcelo F, Alfredo F, de la Fuente R, Natalia C, Luquez H, Recuero Y, Becchetti N, Ruiz M, Costantino M, Vazquez G, Guzman C, Pelatia P, Maffei L, Sassone S, Yantorno M, Prado G, Khron B, Maldonado N, Gustavo L, Veronica V, Marino J, Elizabeth A, Alejandra C, Oscar R, Azize G, Gallardo M, Escudero M, Vargas E, Ramos H, Lucero C, Najenson M, Crocci I, Chiesa A, Nardone L, Dominguez S, Zanini A, Manghi F, Grossman M, Giudice G, Romeo A, Piskorz D, Miguel C, Susana D, Noeli U, Rosa S, Martin V, Soledad A, Virginia M, Lorena G, Prado A, Veronica L, Eduardo H, Adolfo P, Florencia W, Rista L, Scolari C, Rojas N, Bertolio V, Zarandon R, Jair S, Orlando C, Sanabria H, Ignacio D, Viviana C, Marina R, Sarjanovich R, Scaro G, Huerta C, Mana M, Gutierrez M, Dain A, Gavicola R, Sessa H, Sacripanti J, Felman R, Vilarino P, Sicer M, Lagrutta M, Sala J, Casabella T, Cecilia H, Carlos B, Vines G, Javier R, Vico M, Lanchiotti P, Martella C, Torres L, Villarino A, Molina M, Martinez J, Farias C, Bertola S, Rojas M, Guzman P, Nisi J, Martinez D, Barrionuevo M, Vita N, Lopez A, Vottero E, Giuliano M, Paron L, Vogel D, Mele P, Imposti H, Dominguez A, Zaidman C, Fernando G, Beck M, Beltrame P, Chemello D, Junior R, Abreu A, Fernandes V, Saboia J, Rodrigues L, Carvalho M, Gurgel M, Gadelha D, Ramos C, Borba V, Golbert M, Pitthan M, Golbert L, Valentini R, Canani L, Gross J, Valenti A, Sartori C, Dutra O, Azevedo E, Azevedo A, Vaz R, Vaz H, da Costa F, da Costa L, Panarotto D, Lain F, Camazzola F, Dellomea B, Rech R, Pizzato P, Nunes C, Jaeger C, Silveira D, Wagner L, Machado L, Rea R, de Bem A, Alves J, Jonasson T, Malucelli F, Betti R, Lerario A, Lisboa H, Bem J, Tres G, Tavares C, Nardi A, Pozzatto M, Backes L, Reolao J, Scariot E, Ziguer E, Baldissera D, Griz L, Antunes D, Victor F, Freire K, Barros A, Costi B, Sa M, Carneiro A, Felicio J, Felicio K, Penha P, Ferreira J, Melo F, Alves A, Souza A, Costa L, Pinheiro D, Turatti L, Augusto G, Leanca C, Santomauro A, Forti A, Sena R, Marinho A, Facanha C, de Souza K, de Souza A, de Queiroz W, Leite S, Vieira S, Gubert L, Olsen A, Piazzetta G, Fuck A, Ferreira M, Fortes J, Brandao T, Alves F, Radice E, dos Santos J, de Almeida R, Franco D, Saporito W, Eliaschewitz F, de Siqueira K, Bona R, Genestreti P, de Castro D, Visconti G, Sampaio C, Palhares F, Konigsfeld H, Alves E, Feder C, Leao B, Saraiva J, Rodovalho S, Costa M, Pires N, Figueiredo E, Werner G, Garcia J, de Paiva I, Quirino B, Botelho R, da Silva R, Navarro A, Lourenco C, Pereira A, Arantes F, Boner D, Saad J, Falchetto E, Washizu E, Mandil A, Pimenta N, Tofani F, Fonseca T, Teixeira L, Maia L, Lemos M, Mouco O, Nakazone M, Weiand L, Bohn J, Hissa M, Araripe F, Carvalho F, Cancado G, Wang R, Chacra A, Fusaro A, de Mendonca E, Cercato C, Halpern A, Alves B, Braile M, Sestito R, Mustafa E, Ferreira V, Sbardellini B, de Almeida P, Guimaraes F, Piedade M, Bienert I, Braga J, Daher R, Hirakawa T, Terra E, Farias E, Figueiredo M, Lima L, Moraes K, Avelino I, Flato U, Plavnik F, Portes E, Moreira M, Vendramini M, Veloso R, Padilha M, Rodrigues A, Adam R, Santos S, Sayeg N, Guerrero D, Madeira M, Siqueira J, Pinheiro R, Villacorta A, Mellazi A, Braga T, Kaiser S, Paolino B, Lefterov I, Marinchev A, Angelova S, Klyuchkova N, Lybomirova Z, Kerekovski Y, Kuneva T, Penkova D, Levterov G, Videnova E, Georgieva P, Shinkov A, Borissova A, Vlahov J, Dakovska-Dekova L, Lucheva M, Luchev P, Temelkova M, Borisova K, Tsenov S, Andreeva V, Margaritov V, Arasheva G, Lozanov L, Borisov R, Gorcheva D, Henein S, Whatley S, Boutros M, Kalyniuk N, Berlingieri J, Nisker W, Hoag G, Hepburn D, Harvey M, Manjoo P, Yale J, Sherman M, Tsoukas M, Rehman W, Mason M, Santerre M, De Kock J, Barkhuizen F, Rooke C, Gill C, Kooy J, Burgoyne G, de Kock J, Degen G, Hockman L, Invik R, Roberts P, Ward K, Alasaad H, Susan A, Davies V, Gupta N, Milhalidis J, Grossman L, Agawal N, Yared Z, Rwaheed, Nouhad S, Nahla A, Khandwala H, Warwick A, Wadehra D, Manan A, Vecchiarelli J, Aslam N, Ferrao A, St-Maurice F, Collette R, Davey B, Nawaz S, Coutu B, Costi P, Greiss I, Mansour F, Raymond J, St-Phard W, Nadra I, Della Siega A, Barahona L, Klinke P, Contractor H, Fryer M, Chandra N, Conti B, Telzer L, Sorensen S, Lounsbury N, Martin E, Mitchell L, Pelzer E, Nelson S, Jones M, Cox J, Luco G, Trhoughton T, Labonte R, Chouinard G, Frechette A, Rheaume M, Cusson J, Faucher J, Dery V, Kelly A, Miranda B, Al-Kayssi N, Malette P, Rheault P, Fredette P, Dumas R, Palardy J, Belanger A, Boucher P, Doyon B, Charbonneau J, Bailey G, Odendaal M, Stephan K, Badenhorst J, Knight D, Thurgood A, Johnston M, Cooper-Rosen E, Jagger R, Green M, Weisnagel S, Gangloff A, Bergeron J, Pesant Y, Chevalier P, Woo V, Hurd C, Ruckert G, Lira J, Navarro G, Venegas M, Gonzalez P, Montecinos H, Vidal G, Fernandez M, Varas J, Fernandez C, Aguilar J, Marin R, Kindel C, Yovaniniz P, Gherman O, Aravena M, Carvajal J, Macias E, Corrado P, Lazcano M, Garrido B, Charme G, Carrasco J, Vignolo P, Saavedra S, Gajardo V, Saavedra C, Santamaria D, del Castillo B, Balda I, Zurvarra V, Fu G, Jiang D, Huang H, Wang M, Song J, Lu W, Lin Y, Lu Z, Shi Y, Zhong M, Zhao X, Chen D, Zhang G, He Y, Shi P, Chu K, Gao Q, Deng W, Zhang J, Zhang Y, Chen H, Liu E, Xie Y, Lin R, Tan W, Yuan Z, Wang Y, Ren J, Yu H, Luo M, Ma W, Shi W, Xu H, Xu M, Liu G, Dong Y, Bai B, Guo R, Liu X, Gao Y, Li S, Xu X, Liu P, Dong X, Wang S, Fu F, Jiang Q, Meng C, Yin X, Lu Y, Cui Y, Su G, Miao W, Wei F, Zhao Q, Li Z, Gao X, Lozno H, Prada W, Figueroa W, Ordonez A, Quintero E, Vallejo G, Contreras C, Escobar J, Alvaran J, Ortiz L, Marin M, Montoya C, Mendoza J, Manjarres J, Navarro B, Martinez G, Bonfanti A, Perci X, de la Hoz L, Arroyo J, Rendon C, Lopez J, Escobar N, Franco J, Lozano M, Zapata C, Ibarra L, Barrero A, Sarmiento A, Lozada H, Olitte M, Florez L, Munoz C, Quintero G, Correa G, Ruiz S, Dorado A, Causa A, Palma E, Morales A, Arteaga J, Beltran J, Granados M, Rubio A, Dada F, Bueno W, Rivera R, Corredor K, Romero V, Accini F, Palmera J, Ruiz G, Ortega M, Sanchez A, Lora Y, Cano J, Duque S, Thiriez S, Castano M, Giraldo P, Boljkovac Z, Grcic I, Balen M, Zukanovic S, Jeric M, Dvorscak D, Car S, Knezevic A, Herceg D, Franov B, Miskovic V, Bakula M, Hadak A, Superba M, Rubes J, Gornik I, Hamzic J, Ballek L, Sedlackova L, Hejlova J, Galatikova D, Huskova A, Zak P, Flekac M, Mraz M, Potuznik P, Palova S, Novak P, Okenka L, Matuska J, Rohac F, Vondrak K, Reichert P, Shamasna A, Skopek J, Lejskova M, Jiruska M, Lang P, Podoubsky R, Svobodova J, Cifkova R, Jozifova M, Krajcoviechova A, Wolfhart P, Sulc P, Silhova E, Cechakova M, Machova V, Balkova J, Peterka M, Votocek S, Prosecky R, Valis M, Barton P, Tomek J, Pumprla J, Axmannova M, Vitaskova R, Sincl F, Horanska P, Richter B, Malicherova E, Roderova E, Jenickova P, Winkelmann B, Finger C, Klausmann G, Milek K, Schwabe M, Weiss N, Mahlmann A, Werth S, Schmidt C, Schoell I, London M, Steidl E, Orban K, Taeschner H, Bonigut S, Schiefke I, Schwittay A, Kornmann O, Eich A, Franke S, Kis J, Szobota E, Danos P, Beke E, Grosz A, Csecsei G, Ferenczy J, Filo A, Ferencz I, Mihaly E, Baranyi T, Revesz K, Schlezak J, Harcsa E, Dombroczki Z, Kocsis I, Juhasz E, Literati-Nagy B, Kulcsar E, Bezzeg K, Kemeny V, Peterfai E, Buday B, Keltai K, Balo T, Somogyi A, Nagy G, Oroszlan T, Bagosi Z, Bujtor Z, Tabak A, Ferencz V, Domjan B, Tanczer T, Palinkas A, Karolyi H, Kovacs K, Csaszar I, Palhegyi E, Engelhalter G, Horthy R, Vanko E, Szabo G, Sipos G, Szigyarto M, Sebo N, Paragh G, Zsiros N, Szentimrei R, Pal D, Kobling T, Szanto I, Varadi Z, Bajnok L, Szujo S, Nemes O, Bajnok A, Mezosi E, Bodis B, Marton Z, Konyves L, Farago M, Kiss G, Kiss O, Nagy E, Takacs R, Nyitray S, Abraham G, Fehertemplomi K, Deak L, Dezso E, Karneili E, Deeb D, Zloczower M, Mahmid R, Zolotov S, Hochberg I, Elias M, Goldstein L, Poletaev V, Rock W, Koren O, Saliba W, Wolf F, Adawi F, Nimer A, Mosenzon O, Raz I, Potekhin M, Cahn A, Yulian T, Zvulunov E, Israel H, Shpitz D, Bar-Or I, Chananashvili L, Irena L, Dessau H, Halabe A, Vishlitzky V, Nabriski D, Baraf L, Itelman M, Schiff E, Willner N, Fireman-Klein E, Svistunov V, Dotan Y, Pavlichev O, Saig L, Bashkin A, Kuyantseva E, Gershkov S, Nodelman M, Arbel Y, Bogomolny N, Leshem-Rubinow E, Rofe M, Chorin E, Havkuk O, Wainstein J, Feldman D, Fujino Y, Kitamura H, Toriumi Y, Ishiguro H, Naganuma T, Shu S, Suzuki K, Hirota Y, Hayashi T, Hozawa K, Fukui T, Abe Y, Yamauchi K, Maruyama M, Matsumura S, Kozuma R, Nagai Y, Kihara Y, Maeda H, Nakanishi K, Iitsuka T, Hatori M, Shinozaki Y, Akiyama D, Kawabe M, Takei M, Sato A, Kawai Y, Kitajima K, Ide M, Sato N, Morisaki H, Nakashima K, Takayanagi H, Watanabe H, Iwahashi N, Tsujimoto M, Hibuse K, Hata T, Ueno K, Tatsuma H, Wakida Y, Ito T, Mizuno R, Fujita H, Konishi N, Kanehira T, Watanabe R, Miyaoka H, Okada T, Yamamoto M, Okita S, Murakami H, Todo Y, Umeoka F, Hori K, Shiraishi K, Tada F, Shimizu T, Tamai J, Sasaki C, Okuzima Y, Yasuda M, Iwaita Y, Tanaka K, Rha S, Na J, Cho D, Cho Y, Hwang E, Choi T, Won K, Kim H, Kim S, Oh D, Lee J, Choi H, Chung H, Park H, Suh Y, Kim Y, Kim N, Kim K, An J, Kim J, Park K, Kwak S, Kim M, Hwangbo Y, Lee D, Hong A, Kim L, Oh C, Moon S, Jung C, Jin J, Hyun B, Yang Y, Kong S, Yoon K, Yang H, Hong T, Oh J, Park J, Lee H, Choi J, Ahn J, Han S, Park W, Jo S, Suh S, An W, Park M, Lee S, Kim D, Jin H, Seo J, Chung C, Lim J, Huh J, Park I, Yu S, Sim N, Khan S, Albakari N, Sivaraman J, Manaf K, Maharuddin I, Nagendram S, Ali N, Abdul Latiff N, Othman N, Sarip S, Chew E, Mohamed S, Aziz N, Hui K, Lin L, Velaiutham S, Khir A, Lee L, Manikam S, Chooi K, Chang M, Ooi C, Anthony J, Seganathirajah M, Ng O, Ismail N, Cheah C, Ramanathan G, Mui N, Wen F, Choo T, Bin Ruhani A, Jamaludin S, Abidin S, Nor F, Abu Hassan M, Hanari N, Ahmad N, Suan M, Zainul N, Ali S, Sridhar G, Han C, Chin A, Vin L, Kadir K, Zain A, Hussain N, Pusparajah P, Lozano F, Gomez A, Zaccari E, Vigil A, Preciado C, de Leon M, Parra M, Cervantes A, Aguirre E, Orozco E, Gonzalez S, Elizondo R, Flores E, Guerrero M, Flores F, Sanchez J, Perez F, Rodriguez J, Martinez L, Marquez D, Gutierrez B, Flores M, Real M, Campos P, Garcia P, Rios M, Romero E, Perez Z, Tarabay C, Munoz L, Farias J, Gonzalez J, Palestino N, Sanchez L, Carrillo G, Ordonez N, Pech C, Andrade M, Euan J, Ortegon M, Garcia S, Orozco J, Vazquez H, Herrera R, Perez E, Arango A, Ibarra M, Gonzales L, Esperano J, Quintana L, Salazar I, Ruiz L, Barron C, Ballesteros C, Cervera L, Hercilla E, Gomez H, Mesa J, Herrera P, Rodriguez M, Ochoa R, Mora E, Charles C, Silva R, Mijangos J, Diaz C, Zavala C, Baron P, Bernal A, Martinez F, Tlapale M, Ramirez E, Basila A, Munguia R, Tello M, Martinez M, Mulder H, van der Graaff P, Nawaz A, Keller I, Schoofs M, Smak-Gregoor P, Al-Windy N, Bulut S, de Jong J, Maas A, Schaardenburgh P, Imholz B, Heijster J, Hoogenberg K, Smit C, Kooy A, Huvers F, Landewe-Cleuren S, Kars M, van Moorsel D, Wolffenbuttel B, Lutgens H, Schutte E, Gansevoort R, Idzerda N, Westerink J, Weijmans M, Berg J, van Kleef M, Slob M, Jaspers N, Hovens M, Monajemi H, Kobielusz-Gembala I, Zmuda W, Adamczyk M, Konieczny M, Strzelecka-Sosik A, Nowacka E, Krzyzagorska E, Sekulska M, CzajkowskaKaczmarek E, Kaczmarek B, Opawska K, Dabrowska M, Kus W, Wrzesien-Kus A, Piotrowski G, Hotlos L, Ocicka-Kozakiewicz A, Jurowiecki J, Stasinska T, Karczewicz-Janowska J, Jaruga J, ZytkiewiczJaruga D, Krupinska E, Pupek-Musialik D, Bogdanski P, Szulinska M, Skrypnik D, Skokowska E, Bojarska-Los M, Giermkowska-Samek M, Pirog M, Wojnowski L, Jelinska A, Gradzka M, Danyluk A, Lysek R, Sliwinska T, Podrazka-Szczepaniak A, Barney M, Tomczyk A, Necki M, Malicka J, Dudzinska M, KiszczakBochynska E, Markiewicz A, Galbas K, Paciorkowski A, Mazur S, Mazur M, Chmielowski A, Swiatek A, Sobocka B, Wis J, Jozefowska M, Kaczmarek M, Timler M, Cieplucha Z, Lazuka L, Lazuka N, Wittek A, Spyra J, Jasiel-Wojculewicz H, Stefanski A, Wierucki L, Hanczuk A, Misiura M, Szmygel K, Kolcowa O, Orlowska-Kunikowska E, Rutkowski M, Ignaszewska-Wyrzykowska A, Popenda G, Maciejewska J, Mostowy A, WojteckaGrabka M, Grazyna M, Wieslaw K, Barbara K, Kramarczuk E, Wojciech C, Jaroslaw H, Ewa B, Karas P, Agnieszka S, Hanna C, Justyna S, Piotr K, Wozniak I, Mateusz W, Katarzyna W, Jacek F, Andrzej J, Cymerman K, Gmytrasiewicz M, Zambrzycki J, Krysiak-Kowaluk H, Klodawska K, Klszczewski Z, Zieleniewski J, Opadczuk P, Urbanska K, Faran-Grabowska K, Szczepanik T, Siegel A, Kleczek A, Kincel K, Nowak D, Slowik-Gomulka L, Watemborska-Matuszyk G, Lampart J, Strozik-Krecichwost A, Dziewit T, Broncel M, Wojcik-Odyniec J, Jakubczyk E, Wierzbicka K, Witowicz A, Jedrych B, Korczyk P, Socik-Pojawa M, Monteiro P, Monteiro S, Mendes P, Soares F, Mendes S, Leite L, Vicente J, Santos M, Ferreira A, Alves P, Rosario F, Garrao A, Duarte L, Rogado C, Duarte R, Laginha T, Matos P, Raposo J, Mariz J, Teixeira J, Capela C, Leitao A, Cardiga R, Alface M, Augusto S, Basto L, Cunha A, Rei D, Dantas J, Verdasca I, Andrade L, Silva A, Suarez M, Dias V, Silva J, Pereira N, Goncalves M, Goncalves A, Silveira A, Sampaio A, Dias A, Diogo M, Vilaca C, Cif A, Calin T, Elena S, Crisan C, Adina S, Ramona S, Anghel V, Simona C, Turcu L, Mihaela V, Cosma D, Cristina H, Marius-Calin H, Negrisanu G, Andreea-Andrada M, Maria-Mihaela V, Camelia T, Oana P, Monia A, Onaca A, Mircea O, Mot A, Stolea V, Elena N, Barbonta D, Cristian B, Oana S, Popescu A, Madalina M, Coman A, Anca C, Constantinescu S, Mircea C, Diaconu-Sotropa M, Ene D, Pintilei E, Mihai G, Delia R, Toarba I, Simona H, Negru D, Flaminzeanu F, Iulian C, Maria-Cristina C, Doros R, Cleo S, Sorin B, Demian L, Mihai S, Raul B, Ioana A, Nicolau A, Cosmin P, Isabela G, Elena C, Ileana T, Valuyskikh E, Miroshnichenko E, Klementyeva N, Zelman O, Chumakova G, Vigel A, Leonova N, Pergaeva Y, Stefanovskaya O, Pushkareva S, Antoshkina L, Zheleznova N, Iveitsman, Barbarash O, Zvereva T, Zhuravleva E, Zavyrylina I, Usoltceva E, Savostyanova Y, Kupriyanova T, Krivoshapova K, Kondyukova N, Inozemceva A, Argunova Y, Tsyba L, Belenky D, Mariich O, Terekhova A, Tsygankova O, Kuznetsova E, Nagibovich G, Ivchenko Y, Dobronravov V, Dobronravov A, Bush M, Trofimenko I, Vishnevsky A, Zikov V, Kositsyn D, Palzman Z, Spiridonova T, Rodina N, Polozhentsev S, Mamedova L, Panov A, Abesadze I, Alugishvili M, Ivashkin V, Drapkina O, Korneeva O, Zyatenkova E, Glinkina I, Poluboyarinova I, Gurova O, Raykhman A, Vertkin A, Rodykova I, Shamaeva K, Petrovskaya T, Uzueva E, Milovanov Y, Milovanova S, Milovanova L, Markina M, Dobrosmyslov I, Markov V, Afanasiev S, Babich E, Belokopytova N, Demyanov S, Maximov A, Maximov I, Rebrova T, Shtatolkina M, Masin A, Demko A, Chuyko O, Pronina A, Charf G, Akatova E, Urlaeva I, Nikolin O, Khovaeva Y, Ermachkova L, Burdina E, Shvalb P, Suchkov I, Pshennikov A, Gryaznov S, Rymar O, Dolinskaya Y, Bahareva Y, Mustafina S, Sherbakova L, Ovsyannikova A, Bolshakova O, Polunicheva E, Dora S, Agafyina A, Yashina A, Vasilieva I, Yakhontova P, Selivanova S, Kargapoltseva O, Shilina N, Bayramova G, Sorokin I, Astamirova K, Kuchuk P, Koniushenko D, Malykh N, Dvorkin M, Krovelets T, Konovalova K, Seeber M, van Niekerk F, Siebert H, Steenkamp W, Wiid S, Noeth M, Siebert R, Breedt J, Bouwer J, Kapp C, Venter T, Rayner B, Trinder Y, Rheeder P, 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Satyavolu S, Dev D, Yalamanchili H, Sumeyye C, Fernandes H, Chaleff F, Jancko M, Trenche S, Kaplan W, Wilcox S, Goisse M, Rua M, Black J, Chapman K, Suh D, Yan L, Song D, Chanara S, Houchin V, McKeinness A, Sotolongo R, Gutierrez K, Miranda-Palma B, Solano M, Jain M, Needell J, Banerjee A, Jarratt M, Hantel S, Lees K, Welty F, Freedman S, Parhofer K, Birkeland K, McGill J, Tijssen J, Clemmensen P, Pehrson S, Grande P, Januzzi J, Wood M, Petrie M, Sairanen T, Tatlisumak T, Soinne L, Kase C, Turan T, Mann J, Agarwal R, Fogarty D, Navaneethan S, Srinivas T, Forsmark C, Frossard J, Gelrud A, Mayerle J, Lee R, Heist R, Sullivan R, Buchbinder E, Chodak G, Edelman M, Thompson V, Coles A, and CARMELINA Investigators
- Subjects
cardiovascular disease ,type 2 diabetes mellitus ,heart failure ,chronic kidney diseases - Abstract
Background: Individuals with type 2 diabetes mellitus are at increased risk for heart failure (HF), particularly those with coexisting atherosclerotic cardiovascular disease and/or kidney disease. Some but not all dipeptidyl peptidase-4 inhibitors have been associated with increased HF risk. We performed secondary analyses of HF and related outcomes with the dipeptidyl peptidase-4 inhibitor linagliptin versus placebo in CARMELINA (The Cardiovascular and Renal Microvascular Outcome Study With Linagliptin), a cardiovascular outcomes trial that enrolled participants with type 2 diabetes mellitus and atherosclerotic cardiovascular disease and/or kidney disease. Methods: Participants in 27 countries with type 2 diabetes mellitus and concomitant atherosclerotic cardiovascular disease and/or kidney disease were randomized 1:1 to receive once daily oral linagliptin 5 mg or placebo, on top of standard of care. All hospitalization for HF (hHF), cardiovascular outcomes, and deaths were prospectively captured and centrally adjudicated. In prespecified and post hoc analyses of HF and related events, Cox proportional hazards models adjusting for region and baseline history of HF were used. Recurrent hHF events were analyzed using a negative binomial model. In a subset of participants with left ventricular ejection fraction captured within the year before randomization, HF-related outcomes were assessed in subgroups stratified by left ventricular ejection fraction > or 50%. Results: CARMELINA enrolled 6979 participants (mean age, 65.9 years; estimated glomerular filtration rate, mL/min per 1.73m(2); hemoglobin A1c, 8.0%; 62.9% men; diabetes mellitus duration, 14.8 years), including 1873 (26.8%) with a history of HF at baseline. Median follow-up was 2.2 years. Linagliptin versus placebo did not affect the incidence of hHF (209/3494 [6.0%] versus 226/3485 [6.5%], respectively; hazard ratio [HR], 0.90; 95% CI, 0.74-1.08), the composite of cardiovascular death/hHF (HR, 0.94; 95% CI, 0.82-1.08), or risk for recurrent hHF events (326 versus 359 events, respectively; rate ratio, 0.94; 95% CI, 0.75-1.20). There was no heterogeneity of linagliptin effects on hHF by history of HF at baseline, baseline estimated glomerular filtration rate or urine albumin-creatinine ratio, or prerandomization left ventricular ejection fraction. Conclusions: In a large, international cardiovascular outcome trial in participants with type 2 diabetes mellitus and concomitant atherosclerotic cardiovascular disease and/or kidney disease, linagliptin did not affect the risk of hHF or other selected HF-related outcomes, including among participants with and without a history of HF, across the spectrum of kidney disease, and independent of previous left ventricular ejection fraction. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01897532.
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- 2019
11. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk The CARMELINA Randomized Clinical Trial
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S, Park W, Jo S, Suh S, An W, Park M, Lee S, Kim D, Jin H, Seo J, Chung C, Lim J, Huh J, Park I, Yu S, Sim N, Khan S, Albakari N, Sivaraman J, Manaf K, Maharuddin I, Nagendram S, Ali N, Abdul Latiff N, Othman N, Sarip S, Chew E, Mohamed S, Aziz N, Hui K, Lin L, Velaiutham S, Khir A, Lee L, Manikam S, Chooi K, Chang M, Ooi C, Anthony J, Seganathirajah M, Ng O, Ismail N, Cheah C, Ramanathan G, Mui N, Wen F, Choo T, Bin Ruhani A, Jamaludin S, Abidin S, Nor F, Abu Hassan M, Hanari N, Ahmad N, Suan M, Zainul N, Ali S, Sridhar G, Han C, Chin A, Vin L, Kadir K, Zain A, Hussain N, Pusparajah P, Lozano F, Gomez A, Zaccari E, Vigil A, Preciado C, de Leon M, Parra M, Cervantes A, Aguirre E, Orozco E, Gonzalez S, Elizondo R, Flores E, Guerrero M, Flores F, Sanchez J, Perez F, Rodriguez J, Martinez L, Marquez D, Gutierrez B, Flores M, Real M, Campos P, Garcia P, Rios M, Romero E, Perez Z, Tarabay C, Munoz L, Farias J, Gonzalez J, Palestino N, Sanchez L, Carrillo G, Ordonez N, Pech C, Andrade M, 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L, Ocicka-Kozakiewicz A, Jurowiecki J, Stasinska T, Karczewicz-Janowska J, Jaruga J, ZytkiewiczJaruga D, Krupinska E, Pupek-Musialik D, Bogdanski P, Szulinska M, Skrypnik D, Skokowska E, Bojarska-Los M, Giermkowska-Samek M, Pirog M, Wojnowski L, Jelinska A, Gradzka M, Danyluk A, Lysek R, Sliwinska T, Podrazka-Szczepaniak A, Barney M, Tomczyk A, Necki M, Malicka J, Dudzinska M, KiszczakBochynska E, Markiewicz A, Galbas K, Paciorkowski A, Mazur S, Mazur M, Chmielowski A, Swiatek A, Sobocka B, Wis J, Jozefowska M, Kaczmarek M, Timler M, Cieplucha Z, Lazuka L, Lazuka N, Wittek A, Spyra J, Jasiel-Wojculewicz H, Stefanski A, Wierucki L, Hanczuk A, Misiura M, Szmygel K, Kolcowa O, Orlowska-Kunikowska E, Rutkowski M, Ignaszewska-Wyrzykowska A, Popenda G, Maciejewska J, Mostowy A, WojteckaGrabka M, Grazyna M, Wieslaw K, Barbara K, Kramarczuk E, Wojciech C, Jaroslaw H, Ewa B, Karas P, Agnieszka S, Hanna C, Justyna S, Piotr K, Wozniak I, Mateusz W, Katarzyna W, Jacek F, Andrzej J, Cymerman K, 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Abesadze I, Alugishvili M, Ivashkin V, Drapkina O, Korneeva O, Zyatenkova E, Glinkina I, Poluboyarinova I, Gurova O, Raykhman A, Vertkin A, Rodykova I, Shamaeva K, Petrovskaya T, Uzueva E, Milovanov Y, Milovanova S, Milovanova L, Markina M, Dobrosmyslov I, Markov V, Afanasiev S, Babich E, Belokopytova N, Demyanov S, Maximov A, Maximov I, Rebrova T, Shtatolkina M, Masin A, Demko A, Chuyko O, Pronina A, Charf G, Akatova E, Urlaeva I, Nikolin O, Khovaeva Y, Ermachkova L, Burdina E, Shvalb P, Suchkov I, Pshennikov A, Gryaznov S, Rymar O, Dolinskaya Y, Bahareva Y, Mustafina S, Sherbakova L, Ovsyannikova A, Bolshakova O, Polunicheva E, Dora S, Agafyina A, Yashina A, Vasilieva I, Yakhontova P, Selivanova S, Kargapoltseva O, Shilina N, Bayramova G, Sorokin I, Astamirova K, Kuchuk P, Koniushenko D, Malykh N, Dvorkin M, Krovelets T, Konovalova K, Seeber M, van Niekerk F, Siebert H, Steenkamp W, Wiid S, Noeth M, Siebert R, Breedt J, Bouwer J, Kapp C, Venter T, Rayner B, Trinder Y, Rheeder P, Delport E, Mathijs S, Soma P, van Zyl D, Strydom M, Marais A, Badat A, Hansa S, Fourie D, Walton T, Engelbrecht J, Jansen J, Roos J, du Toit S, Lehloenya K, van Zyl L, van Zyl F, Naude M, Mookadam M, van der Merwe A, Trokis J, Lombard L, Coetzee K, Ismail S, Bruning H, Latiff G, Yasmin O, Pillay T, Mohamed Z, Dawood S, Stapelberg A, Abrahams P, Jurgens J, van Heerden P, Swart E, Botha C, Meeding J, Hemus A, Oosthuysen W, Visagie G, Fourie N, Hutton P, van der Merwe N, Chelin N, Everton T, Duki M, Ghila N, Joshi M, Hira M, Madueno F, Martinez B, Sebastian N, Mercadal L, Isbert S, Gonzalez I, Asencio J, Figueras M, Rivas M, Garcia H, Fusalba A, Geat D, Cambra G, Sastre J, Castro F, Mas A, Portillo C, Serrano I, Hernandez S, Fajardo F, Juan C, Ferrer J, Peralta F, Padin C, Mauricio D, Madorell B, San Miguel F, Pedrol N, Trescoli C, Montanana C, Gonzalo M, Capellan J, Estrella A, Martinez C, Montesinos I, Loscos A, Coronado J, Perez J, Castillo B, Alonso C, Quesada V, Teruel J, Perez S, Lama M, del Rio E, Zlova T, Ponomarenko K, Karpenko O, Bezuglova S, Mitskevych L, Kizim S, Nevolina I, Katerenchuk V, Liudmyla B, Ivan K, Rudyk I, Olena M, Anna I, Ganna B, Topchii I, Semenovykh P, Yulia Y, Mykhalchyshyn G, Kirienko D, Kobiliak N, Bodnar, Mykhalchyshyn, Pertseva N, Olena G, Tomashkevych H, Korpachev V, Prybyla O, Kovalchuk A, Kushnarova N, Zinych O, Tseluyko V, Andriy Z, Olga R, Mankovskyy B, Zherdova N, Lykhoshapko O, Logoida P, Godlevska O, Olena V, Olga C, Gyrina O, Alifer O, Dozhuk K, Pekhenko V, Gorobets N, Korneichuk A, Makarenko E, Martynyuk L, Martynuyk O, Stanislavchuk M, Larysa P, Natalia S, Botsyurko V, Kostitska I, Dzeman O, Ablitsov Y, Ivaseiko S, Konovart O, Sandurska S, Vendzilovych Y, Samoylov O, Iryna C, Rozhkivska L, Ulyanchenko I, Kateryna V, Orlenko V, Ivaskina K, Tronko M, Tronko K, Pashkovska N, Stankova N, Vynnychenko L, Bolotnikova N, Demokhova N, Reshotko D, Popova A, Dr Bogdana, Tetiana S, Svitlana D, Oksana R, Vlasenko M, Litvinova S, Semenyuk I, Fishchuk O, Mostovoy Y, Tkachenko T, Ovcharuk M, Rasputina L, Vakaliuk I, Tymochko N, Drapchak I, Petrovska L, Lai W, Yen H, Voon W, Lin T, Cheng K, Chiu C, Chu C, Hsu P, Chiang C, Li Y, Kuo C, Lin S, Chao T, Yu W, Sung S, Wang K, Lu T, Shih K, Wu C, Chiang F, Hwang J, Tsai C, Juang J, Jeng J, Tang S, Lai C, Cheng C, Hsieh I, Hsieh M, Chen C, Lee C, Pai P, Ko P, Wang T, Chen T, Wu H, Chang S, Chen K, Hsieh L, Chou C, Jiang J, Lee M, Huang J, Chen J, Chiu K, Tsai L, Chen P, Saxena M, Collier D, Vaidya B, Harman S, Ramell M, Davies M, Chatterjee S, Meakin L, Quinn M, Bain S, Mallipedhi A, Min T, Bashir J, Blagden M, Ali J, McCrimmon R, Brennan G, Malcolm E, McDonald D, Pearson E, Illsley G, Darzy K, Winocour P, Hanif W, Cockwell P, Charlton M, Thekkepat S, Howat I, Devers M, Patrick J, Wyatt N, Smith C, Singh B, Nicholas J, Gillani S, Green F, Bell E, Boyle J, MacKin S, Livingstone R, Arif A, Syed M, Hammoud J, Sparks J, Anderson M, Tumey R, Condit J, Reddy M, Abalos-Galito M, Rebecca J, Barker T, Seaton B, Campbell E, Kompanik H, Jayson L, Huffman C, Bialow M, McDonnell G, McCaffrey J, Manis C, DeLuca E, Levins J, Bartlett M, Anorga K, Franco M, Gentry P, Hodge D, Pohil R, Rschultz, Leggett R, Blair L, Gisler J, Niegos F, Osburn M, Parma K, Schendel S, Stines L, Winnie M, Wu P, Canales J, Yu J, Cornett G, Beavins J, Hyde D, Zapinski D, Johnson T, Levinson D, Ahmed A, Kenny B, Kuehl A, Bates C, Jantzi C, Ananthula P, Shafer J, Louthan J, Bays A, Stapleton A, Staton P, Strum D, Taylor P, Smith A, Rapp R, Bao S, Randolph C, MacGillivray B, Schuster R, Harden T, Barnella C, Dunnam T, Whiles R, Bolick C, Brockmyre A, Plucker S, Marshall C, Poteet C, Morin D, Tavel E, Averill N, McFann A, Purcell D, Dixon T, Corey E, Goss J, Drescher R, Irfan M, Naeem M, Egelhof R, Mehta P, Koehler T, Walia J, Fernandez J, Bedel G, Preet R, Bhuchar S, Ahmed F, Onyema D, Benchabbat A, Kohanbash L, Miller P, Lalinde M, Carrithers E, Patterson R, Raube-Miceli A, Martinez A, Harris B, Levy R, Siev E, Berlin H, DiMattia M, Sugimoto D, Dugas J, Benson M, Stegemoller R, Schmoll M, Kinnaman S, O'Connor T, Powel T, Rudolph L, Lewiecki M, Best E, Chavez J, Garcia M, Cohen R, Colman D, Ocampo M, Heaney L, Rappley G, Quezada I, Santos V, Nikfarjam A, Reyes M, Rodriguez R, Josephs L, Hernandez R, Flores P, Espinoza L, Mejia W, Pedraza Z, Castaneda R, Laguerre J, Cook R, Patel R, Werner H, Blank R, Small S, Andersen J, Holmes D, Farmer M, Wiener V, Pharr W, Bray B, Beekman J, Anderson A, Andrawis N, Gabra N, Moche T, Marty S, Galvez O, Reyes R, Garcia R, Lerma G, Pliquin B, Mayfield R, Durham N, Phillips R, Baran A, Kondo N, Dempsey S, Kufs W, Laddis T, Zimmer K, Van Depol M, Dweck L, Kestler M, Werner N, Ashraf M, Quick A, Schallert G, Sligh T, Trueba P, Batista J, Martinez T, Moya J, Amarales V, Santos E, Torres P, Diaz T, Diaz J, Hodish I, Else T, Buras E, Moratis A, Valika S, Rahman A, Malalis W, Box E, Box P, Kerwood B, Nagaeva J, Metz C, Hinnant J, Griswell D, Philbeck A, Dukkipati R, Shaarawy R, Patak R, Kaye W, Steinsapir J, Horowitz B, Denenberg M, Reynolds C, Jenkinsdr M, Adlakha A, Hicklin H, Peelman J, Lerman S, Lamkin S, Smith S, Gould G, Cheung D, Stephen Z, Leigh T, Norwood P, Chelsea F, Trejo R, Neolms K, Bache R, Dinnerstein A, Sachson R, Aronoff S, Mendez A, Brooks S, Jones L, Dorfman S, Schill J, Leuck, Miklius A, Maw K, Hahn J, Gamarra L, Buynak R, Smith M, Ames J, Volom P, Anderson R, Desouza C, Shivaswamy V, Lefebvre G, Schweppe L, Berenguer R, Nelson R, Mas L, Gonzalez N, Palacio J, Bartkowiak A, Dilling J, Jordan T, Geishauser J, Jordan R, Arias E, Griffin C, Fisher M, Bryant C, Schnitz W, Kipgen W, Kasper J, Lopez R, Wright E, Thomas J, Weinstein D, Emerick G, Mendelson R, Aqua K, Lafaille J, Seco G, Garcia G, Cubillas M, de Souza J, Schneider A, Tjaden J, Goswami G, Schubart U, Kishore P, Bravo W, Guerrero J, Bertoli-Avella M, Reyes C, Dominguez M, Ramos S, Columbie A, Ares-Romero P, Hechavarria J, Villaverde M, Doyle N, Sherrod T, Krishnaswamy K, Aamir S, Giddaluri P, Guevara S, Kazmi P, Thomas P, Popeil L, Albright D, Pimentel S, Mould E, Cox M, Alderson T, Conrow J, Sandberg J, Raam S, Suresh B, Lafave J, Lorenz T, Johnston J, Fereidouni S, Mahadevan A, West R, Nelson A, Scott K, Ansari S, Khan B, Rastogi A, Saumell F, Gonzalez G, Torres E, Elias R, Hart T, Lozano J, Gudavilla G, Savin V, Khan A, Wiegmann T, Goel A, Gomes M, Fernandez-Gonzalez M, Gustavo F, Ivan C, Chiong R, Llerena S, Jimenez M, Oram D, George D, Lewis J, Kiefer J, Dollman A, Edje L, Pastor F, Kandath D, Lorch D, Graves A, Powell R, Hooker T, Shah S, Gomez N, Miranda F, Rosales J, Bayona I, Gomez Y, Guedes R, Rodriguez Y, Wahlen J, Jonathan W, Spencer H, Michael W, Kumar U, Govindariju K, Ordonez S, Aguirre H, Sulur P, Agarwal N, Peters L, Kaviani B, Fomenko O, Firek A, Loreen W, Ronald F, Olha F, Parrillo J, Janovitz R, Hutchinson R, Delgado E, Ashley A, Robinson S, Barbel-Johnson K, Timothy L, William C, Al-Karadsheh A, Hooper L, Suarez J, Perez D, Guerrero V, Tung D, Loo C, Sodolak K, Michaelis C, Jackson R, Covington D, Wise J, Tran T, Messina T, Torres D, Falcone J, Barettella M, Patel K, Ribo A, Mattews T, Amendolare D, McGeehan J, Corder C, Black C, Hearne S, Bounds C, Cinderella J, Etherton J, Kiem S, Treuth M, Burke B, Tivikaran V, Howard S, Miller C, Neff H, Giullian J, Mcrae J, Surratt D, Phillips J, Kretchmar J, Valdes M, Cruz J, Navarro E, Zewail A, Tai-Chi-Kwo, Stevens J, Diane S, Kim T, Gregory L, Neal S, William S, Sangrigoli R, Gejer E, Stoller S, Jeffrey D, Colar S, Kenneth W, Farris N, Mooney S, Jamal A, Nitin B, Syed R, Andrew Y, Christopher W, Abid R, Claudio G, Mojtaba M, Amna R, Michael B, Vincent T, Cherlin R, Ashton R, Pudi K, Julian W, Stephen K, Ronald A, Frias J, Kelly S, Hsia S, Clemens P, Cara H, Farley B, Raible L, Oliveros O, Hafeez H, Pecci P, Bagga-Malhotra S, Reza R, Jamal M, Mulgado M, Guevara A, Vela M, Ochoa H, Melliza T, Pena G, Awua-Larbi S, Shafi M, Alausa T, Polster S, Earl J, McNeill R, Farrington C, Carr K, Nabat M, Matthew S, Yvette E, Handelsman Y, Delkhah S, Ismail Y, Janna C, Akhtar A, Neiman A, Blumenthal S, Colleen V, Schmidt D, Ashraf E, Bhargava A, Khoo T, Langel C, Theuma P, Wright D, Fitzgerald K, Hitchcock J, Capasso-Gulve E, Wolff E, Umpierrez G, Priyathama V, Francisco P, Dawn S, Quraishi A, Kahn B, Ferro F, Hertz B, Phelps J, Campbell A, Downing J, Pangtay D, Pangatay S, Villagran-Solis K, Haseeb M, Rettig K, Kwan R, Cox R, Slimak V, So A, Schmedtje J, Chang A, Douglas Z, McGarity W, Jestel J, Kanade P, Julie J, Asher R, Canaan Y, Perez A, Alonso I, Cutchin R, Koser A, Adeola Y, Brito S, Stocks J, Frandsen B, Weigelt M, Stehouwer E, Ince C, Stephen P, Shadi B, Jeffrey C, Thethi T, Carpio G, McDuffie R, Moreau C, Stell C, Katalenich B, McKendall-Lewis C, Htun W, Conroy K, Lovre D, Galagan R, Olmeda C, Sihota A, Barton A, Beasley R, Nankivel P, Aberle M, Machin I, Porras J, Rodriguez D, Albornoz A, Haidar A, Lopez-Santini R, Rivero G, Robins G, Colyar L, Hutchins C, Sturm D, Hart K, Phillips T, Montgomery C, Albrecht W, Fehlis K, Overman D, Box M, Villarreal-Martinez D, David-Svatek D, Ajani D, Shaikh Z, Wheeler K, Brown M, Ghosh C, Bandukwala I, Kleber S, Madden J, Bishara M, Perry K, Paoli-Bruno J, Abreu E, Espiritu R, Zmeili O, Christensen T, Grubb S, Beloff S, Caugh A, van Dijk C, Yalavarthy R, DeGraauw J, Fabian S, Gillum D, Corrigan G, Singh H, Jensen K, DeMore S, Montague T, Zieve F, Levy J, Fredrickson S, Tarkington P, Chapla P, Salacata A, Walls U, Iyer R, Nguyen K, Lettman J, Appleman B, Safavie F, Scaliem L, Eder F, Maklad S, Schlaen B, Molstead J, Hartwell J, Hubish D, Little R, Rando K, Kelly R, Drury M, Young P, Wininger S, Harman A, Daza R, Robbin S, Sanchez M, Rivera I, Garcia-Estrada M, Iglesias N, Dobs A, Andrade A, Falkowski S, Parrott T, Koon A, Wood T, Burkett E, Chavous K, Gupta A, Estes C, Loud D, Rhodes S, Chen M, Bromley L, Palma R, Kattan D, Kirk U, Tatu H, Stamatin R, Lupea S, Frasie M, Colfer H, Kane L, Teklinski A, Gadowski G, Levanovich P, Saba F, Confident L, Hossain S, Steinberg B, Philippe B, Choroenthkongtrakal S, Boccalano F, Anand R, Syam V, Manohar A, Suresh P, Madhusudhan P, Patel P, Cambier P, Klonaris J, Cheng W, Fisher S, Schelle M, Reese L, McLean S, Poock J, Hoens J, Rosie A, Welshons R, Dean J, Kuhlman P, Luke R, Lohrbauer L, Cunningham M, Buday P, Lehmann M, Chrzanowski K, Fletcher A, Hargrove J, Harris F, Debs-Perez G, Maiquez A, Cordoves L, Georgescu M, Tayoun H, Munoz F, Ortiz D, Munoz G, Hamzeh I, Misra A, Zhang L, Forgosh L, Loria K, Roncari C, Hommerding J, Morris G, Lebron C, Blake K, LaVenture K, Lange C, Levinson L, Baungarten T, Edevante S, Shawley S, Moyer H, Elliott K, Iachini K, Rajan R, Davis C, Shattuck A, Simon W, Lakin G, Secrist N, Buth D, Steere D, Talbot K, Singh N, Mascolo R, Sloan S, Kmetzo J, Brown J, Carter L, Lawrence M, Arauz-Pacheco C, Lender D, Kozlow W, Cavanaugh L, Wilson J, Gujja P, Akhter F, Khan M, Mohammed A, Satyavolu S, Dev D, Yalamanchili H, Sumeyye C, Fernandes H, Chaleff F, Jancko M, Trenche S, Kaplan W, Wilcox S, Goisse M, Rua M, Black J, Chapman K, Suh D, Yan L, Song D, Chanara S, Houchin V, McKeinness A, Sotolongo R, Gutierrez K, Miranda-Palma B, Solano M, Jain M, Needell J, Banerjee A, Jarratt M, Hantel S, Lees K, Welty F, Freedman S, Parhofer K, Birkeland K, McGill J, Tijssen J, Clemmensen P, Pehrson S, Grande P, Januzzi J, Wood M, Petrie M, Sairanen T, Tatlisumak T, Soinne L, Kase C, Turan T, Mann J, Agarwal R, Fogarty D, Navaneethan S, Srinivas T, Forsmark C, Frossard J, Gelrud A, Mayerle J, Lee R, Heist R, Sullivan R, Buchbinder E, Chodak G, Edelman M, Thompson V, Coles A, and CARMELINA Investigators
- Abstract
IMPORTANCE Type 2 diabetes is associated with increased cardiovascular (CV) risk. Prior trials have demonstrated CV safety of 3 dipeptidyl peptidase 4 (DPP-4) inhibitors but have included limited numbers of patients with high CV risk and chronic kidney disease. OBJECTIVE To evaluate the effect of linagliptin, a selective DPP-4 inhibitor, on CV outcomes and kidney outcomes in patients with type 2 diabetes at high risk of CV and kidney events. DESIGN, SETTING, AND PARTICIPANTS Randomized, placebo-controlled, multicenter noninferiority trial conducted from August 2013 to August 2016 at 605 clinic sites in 27 countries among adults with type 2 diabetes, hemoglobin A(1c) of 6.5% to 10.0%, high CV risk (history of vascular disease and urine-albumin creatinine ratio [UACR] > 200mg/g), and high renal risk (reduced eGFR and micro-or macroalbuminuria). Participants with end-stage renal disease (ESRD) were excluded. Final follow-up occurred on January 18, 2018. INTERVENTIONS Patients were randomized to receive linagliptin, 5 mg once daily (n = 3494), or placebo once daily (n = 3485) added to usual care. Other glucose-lowering medications or insulin could be added based on clinical need and local clinical guidelines. MAIN OUTCOMES AND MEASURES Primary outcomewas time to first occurrence of the composite of CV death, nonfatalmyocardial infarction, or nonfatal stroke. Criteria for noninferiority of linagliptin vs placebo was defined by the upper limit of the 2-sided 95% CI for the hazard ratio (HR) of linagliptin relative to placebo being less than 1.3. Secondary outcome was time to first occurrence of adjudicated death due to renal failure, ESRD, or sustained 40% or higher decrease in eGFR from baseline. RESULTS Of 6991 enrollees, 6979 (mean age, 65.9 years; eGFR, 54.6 mL/min/1.73m2; 80.1% with UACR > 30mg/g) received at least 1 dose of study medication and 98.7% completed the study. During a median follow-up of 2.2 years, the primary outcome occurred in 434 of 3494 (12.4%) and 420 of 3485 (12.1%) in the linagliptin and placebo groups, respectively, (absolute incidence rate difference, 0.13 [95% CI,-0.63 to 0.90] per 100 person-years) (HR, 1.02; 95% CI, 0.89-1.17; P
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- 2019
12. Expression of NOX1, a superoxide-generating NADPH oxidase, in colon cancer and inflammatory bowel disease
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Szanto, I, Rubbia-Brandt, L, Kiss, P, Steger, K, Banfi, B, Kovari, E, Herrmann, F, Hadengue, A, and Krause, K-H
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- 2005
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13. Coexistence of limit cycles and invariant algebraic curves for a Kukles system
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Chavarriga, J., Sáez, E., Szántó, I., and Grau, M.
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- 2004
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14. Treatment of bile leak following laparoscopic cholecystectomy: the significance of the bile duct of Luschka
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Asztalos, I., Gamal, E.M., Metzger, P., Szanto, I., Altorjay, A., Voros, A., Rozsa, I., and Kiss, J.
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- 1998
15. A cubic Kolmogorov system with six limit cycles
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Lloyd, N.G., Pearson, J.M., Saéz, E, and Szántó, I.
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- 2002
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16. Three limit cycles for a first-order exothermic chemical reaction in a continuous stirred-tank reactor
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Saez, E, Szanto, I, and Monsalve, A
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- 2000
17. High-Throughput Screening of Saliva for Early Detection of Oral Cancer: A Pilot Study
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Szanto, I., primary, Mark, L., additional, Bona, A., additional, Maasz, G., additional, Sandor, B., additional, Gelencser, G., additional, Turi, Z., additional, and Gallyas, F., additional
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- 2012
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18. Expression of mRNA for ROS-generating NADPH oxidases in the aging stomach
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SALLES, N, primary, SZANTO, I, additional, HERRMANN, F, additional, ARMENIAN, B, additional, STUMM, M, additional, STAUFFER, E, additional, MICHEL, J, additional, and KRAUSE, K, additional
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- 2005
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19. Neuronal expression of the NADPH oxidase NOX4, and its regulation in mouse experimental brain ischemia
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Vallet, P., primary, Charnay, Y., additional, Steger, K., additional, Ogier-Denis, E., additional, Kovari, E., additional, Herrmann, F., additional, Michel, J.-P., additional, and Szanto, I., additional
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- 2005
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20. Commentary: The Association Between Insulin Resistance, Depression, and Dementia
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Vischer, U., primary, Szanto, I., additional, and Michel, J.-P., additional
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- 2004
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21. Expression of an α7 duplicate nicotinic acetylcholine receptor-related protein in human leukocytes
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Villiger, Y., primary, Szanto, I., additional, Jaconi, S., additional, Blanchet, C., additional, Buisson, B., additional, Krause, K.-H., additional, Bertrand, D., additional, and Romand, J.-A., additional
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- 2002
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22. New developments in Krebs mixer-settler technology
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Sonntag, A. A., primary, Szanto, I., additional, and Goodman, D. A., additional
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- 1992
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23. An existence of inequality on a fine focus
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Saez, E., primary and Szanto, I., additional
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- 1990
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24. Cubic Kolmogorov system with invariant straight lines
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Saez, E., Szanto, I., and Gonzalez-Olivares, E.
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- 2001
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25. 35th Annual Meeting of the European Association for the Study of Diabetes
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Melander, A., Olsson, J., Lindberg, G., Salzman, A., Howard, T., Stang, P., Lydick, E., Emslie-Smith, A., Boyle, D. I. R., Evans, J. M. M., Macdonald, T. M., Bain, J., Sullivan, F., Juhl, C., Pørksen, N., Sturis, J., Hollingdal, M., Pincus, S., Veldhuis, J., Dejgaard, A., Schmitz, O., Kristensen, J. S., Frandsen, K. B., Bayer, Th., Müller, P., Dunning, B. E., Paladini, S., Gutierrez, C., Deacon, R., Valentin, M., Grunberger, G., Weston, W. M., Patwardhan, R., Rappaport, E. B., Sargeant, L. A., Wareham, N. J., Khaw, K. T., Zethelius, Björn, Lithell, Hans, Hales, C. Nicholas, Berne, Christian, Lakka, H.-M., Oksanen, L., Tuomainen, T.-P., Kontula, K., Salonen, J. T., Dekker, J. M., de Boks, P., de Vegt, F., Stehouwer, C. D. A., Nijpels, G., Bouter, L. M., Heine, R. J., Bruno, G., Cavallo-Perin, P., Bargero, G., D’Errico, N., Borra, M., Macchia, G., Pagano, G., Newton, R. W., Ruta, D. A., New, J. P., Wallace, C., Roxburgh, M. A., Young, R. J., Vaughan, N. J. A., Elliott, P., Brennan, G., Devers, M., MacAlpine, R., Steinke, D., Lawson, D. H., Decallonne, B., Casteels, K., Gysemans, C., Bouillon, R., Mathieu, C., Linn, Thomas, Strate, Christine, Schneider, Kerstin, Funda, D. P., Jirsa, M., Kozáková, H., Kaas, A., Kofronová, O., Tlaskalová-Hogenová, H., Buschard, K., Wanka, H., Hartmann, A., Kuttler, B., Rasmussen, S. B., Sørensen, T. S., Markholst, H., Petersen, J. S., Karounos, D., Dyrberg, T., Mabley, J. G., Haskó, G., Szabó, C., Seissler, J., Nguyen, T. B. T., Steinbrenner, H., Scherbaum, W. A., Cipriani, R., Gabriele, A., Sensi, M., Guidobaldi, L., Pantellini, F., Cerrito, M. G., Scarpa, S., Di Mario, U., Morano, S., Ceolotto, G., Iori, E., Baritono, E., Del Prato, S., Semplicini, A., Trevisan, R., Zerbini, G., Meregalli, G., Asnaghi, V., Tentori, F., Maestroni, A., Mangili, R., Marescotti, C., Vedovato, M., Tiengo, A., Tadjieva, J., Mankovsky, B. N., Van Aken, S., Raes, A., Vande Walle, J., Matthys, D., Craen, M., Hansen, H. P., Lund, S. S., Rossing, P., Jensen, T., Parving, H.-H., Andersen, S., Tarnow, L., Hansen, B. V., Trautner, C., Haastert, B., Ennenbach, N., Willich, S., Tabák, Á. Gy., Orchard, T. J., Spranger, J., Preissner, K. T., Schatz, H., Pfeiffer, A., Cantón, A., Burgos, R., Hernández, C., Lecube, A., Mesa, J., Segura, R. M., Mateo, C., Simó, R., Fathallah, L., Greene, D. A., Obrosova, I., Gilbert, R. E., Kelly, D. J., Cox, A. J., Berka-Wilkinson, J. L., Taylor, H. R., Panagiotopoulos, S., Lee, V., Jerums, G., Cooper, M. E., Hitman, G. A., Aganna, E., Ogunkolade, W. B., Rema, M., Deepa, R., Shanthi-Rani, C. S., Barakat, K., Kumarajeewa, T. R., Cassell, P. G., McDermott, M. F., Mohan, V., Ways, K., Bursell, S., Devries, T., Woodworth, J., Alatorre, C., King, G., Aiello, L. P., Karisen, A. E., Pavlovic, D., Nielsen, K., Jensen, J., Andersen, H. U., Pociot, F., Mandrup-Poulsen, T., Eizirik, D. L., Nerup, J., Lortz, S., Tiedge, M., Lenzen, S., Lally, F. J., Bone, A. J., Darville, M. I., Ho, Y.-S., Sternesjö, J., Sandler, S., Chen, M.-C., Schuit, F., Pipeleers, D. G., Merezak, S., Hardikar, A., Hoet, J. J., Remacle, C., Reusens, B., Bréant, B., Garofano, A., Czernichow, P., Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., Yamauchi, T., Nakano, R., Komeda, K., Eto, K., Tobe, K., Kimura, S., Kadowaki, T., Ide, T., Murakami, K., Tsunoda, M., Mochizuki, T., Ozanne, S. E., Nave, B. T., Wang, C. L., Dorling, M. W., Petry, C. J., Koopmans, S. J., van der Bent, C., Que, I., Radder, J. K., Sebokova, E., Sana, A. K., Klimes, I., Ruderman, N., Morviducci, L., Pastore, L., Morelli, S., Sagratella, E., Zorretta, D., Buongiomo, A., Tamburrano, G., Giaccari, A., Martinenghi, Sabina, De Angelis, Gabriella Cusella, Ravasi, Flavio, Bifari, Francesco, Bordignon, Claudio, Falqui, Luca, Kessler, A., Dransfeld, O., Sasson, S., Tomas, E., Zorzano, A., Eckel, J., Thorsby, P., Rosenfalck, A. M., Kjems, L., Hanssen, K. F., Madsbad, S., Birkeland, K. I., Hamilton-Wessler, M., Markussen, J., Bergman, R. N., Melki, V., Hanaire-Broutin, H., Bessières-Lacombe, S., Tauber, J.-P., Home, P. D., Lindholm, A., Riis, A., Rosenstock, J., Schwartz, S., Clark, C., Edwards, M., Donley, D., Swift, P., Mortensen, H. B., Lynggaard, H., Hougaard, P., Cull, C. A., Neil, H. A. W., Frighi, V., Manley, S. E., Holman, R. R., Turner, R. C., Steiner, G., Davis, W. A., Weeraratna, T., Bruce, D. G., Davis, T. M. E., Vergès, B., Duvillard, L., Pont, F., Florentin, E., Gambert, Ph., Benko, B., Ljubić, S., Turk, Z., Granić, M., März, W., Wollschläger, H., Klein, G., Neiss, A., Wehling, M., Huxtable, S. J., Saker, P. J., Walker, M., Frayling, T. M., Levy, J. C., O’Rahilly, S., Hattersley, A. T., McCarthy, M. I., Orecchio, A., Giacchini, A., Dominici, R., Canettieri, G., Trinti, B., Zani, M., Andreoli, M., Sciacchitano, S., de Silva, A. M., Whitecross, K., Pasco, J., Kotowicz, M., Nicholson, G., Zimmet, P., Boyko, E. J., Collier, G. R., Frittitta, L., Pizzuti, A., Argiolas, A., Graci, S., Goldfine, I. D., Bozzali, M., Ercolino, T., Costanzo, B., Iacoviello, L., Tassi, V., Trischitta, V., Wauters, M., Rankinen, T., Mertens, I., Chagnon, M., Bouchard, C., Van Gaal, L., Sivenius, K., Valve, R., Hakkarainen, V., Niskanen, L., Laakso, M., Uusitupa, M., Beridze, N., Japaridze, M., Kurashvili, R., Dundua, M., Kebuladze, G., Kazakhashvili, N., Offley-Shore, B., Thomas, B., Ghebremeskel, K., Crawford, M., Lowy, C., Eriksson, Ulf J., Martin Simán, C., Wisse, Bert, Gittenberger-de Groot, Adriana C., Wentzel, P., Eriksson, U. J., Wender-Ożegowska, E., Drews, K., Biczysko, R., Bronisz, A., Rość, D., Graczykowska-Koczorowska, A., Kotschy, M., Sokup, A., Kohnert, K. D., Besch, W., Strese, J., Frick, U., Zander, E., Kemer, W., Škrha, J., Kvasnička, J., Kalvodová, B., Hilgertová, J., Schatteman, K., Goossens, F., Scharpé, S., De Leeuw, I., Hendriks, D., Legakis, I. N., Panayiotou, D., Mountokalakis, Th. D., Enderle, M. 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H., Telting, D., van der Zon, G. C. M., Dorrestijn, J., Maassen, J. A., Clapham, J. C., Holder, J. C., Tomlinson, K. M., Pickavance, L., Buckingham, R., Wilding, J., Jacinto, S. M., Harrold, J., Ljung, B., Kjellstedt, A., Thalén, P., Widdowson, P., Williams, G., Oakes, N., Aoki, K., Saito, T., Satoh, S., Mukasa, K., Kaneshiro, M., Kawasaki, S., Hoshino, K., Okamura, A., Sekihara, H., Smith, U., Johansson, A., Nilsson, E., Olausson, T., Nakazawa, T., Suzuki, M., Martinez, J., Murado, P., Azal, Ö., Yönem, A., Çakır, B., Polat, Z., Kutlu, M., Çorakçı, A., Bayraktar, M., Gürlek, A., Koray, Z., Damian, M. S., Linn, T., Laube, H., Arzner, S., Meißner, H.-P., Giunti, S., Comune, M., Cassader, M., Conte, M. R., Sacchi, C., Musso, G., Mecca, F., Depetris, N., Gambino, R., Perin, P. Cavallo, Kawakami, S., Sandqvist, M., Jansson, P.-A., Šindelka, G., Widimský, J., Haas, T., Prázný, M., Mari, A., Nolan, J. J., Uusitupa, M. I. J., Karşıdağ, K., Hacıhanefioğlu, B., Dinççağ, N., Drivsholm, T., Palacios, R. T., Vølund, A., Pedersen, Oluf B., Letiexhe, M. R., Scheen, A. J., Quiñones Galvan, A., Simeoni, M., Basu, A., Uosukainen, A., Mäkimattila, S., Schlenzka, A., Adler, A. I., Levy, J., Stevens, R., Matthews, D., Holman, R., Boland, B. J., Jeanjean, M., Hermans, M. P., Maudoigt, C., Tonglet, R., Robert, A., Quiñones-Galvan, A., Cini, G., Galetta, F., Sanna, G., Gernone, F., Janssen, M. J., Gonera, R. K., Wolffenbuttel, B. H. R., de Leeuw, P. W., Schaper, N. C., Molęda, P., Kuczerowski, R., Czech, A., Tatoń, J., Taddei, S., Patiag, D., Qu, X., Wilkes, M., Gray, S., Seale, J. P., Donnelly, R., Campión, J., Maestro, B., Dávila, N., Carranza, M. C., Calle, C., Hales, C. N., Fernández-Real, J. M., Grasa, M., Pugeat, M., Barret, C., Ricart, W., Lindmark, S., Olsson, T., Tufvesson, M., Loeblein, K., Mehnert, B., Haering, H. U., Rave, Klaus, Heise, Tim, Clauson, Per, Hirschberger, Sabine, Heinemann, Lutz, Claret, M., Nadal, B., Truc, A., Rossi, L., Hildebrand, P., Ketterer, S., Beglinger, C., Keller, U., Gyr, K., Parvin, S., Overkamp, D., Vayreda, M., González-Huix, F., G-Huix, F., Zavaroni, I., Gasparini, P., Massironi, P., Zuccarelli, A., Delsignore, R., Reaven, G. M., Sheu, W. H. H., Lee, W. J., Chen, Y.-T., Iraklianou, S., Tournis, S., Volonakis, I., Spylopoulou, M., Bilianou, E., Melidonis, A., Foussas, S., Güler, Serdar, çakir, Bekir, Demi̇rbaş, Berrin, Gürsoy, Gül, Serter, Rüştü, Aral, Yalçin, Morton, G., Lee, S., Fahey, R., de Silva, A., Cai, X. J., Buckingham, R. E., Arch, J. R. S., Wilson, S., Clausen, J. T., Kristensen, P., Nielsen, P. F., Wulff, B. S., Thim, L., Holness, M. J., Sugden, M. C., Fryer, L. G. D., Munns, M. J., Mannucci, E., Ognibene, A., Cremasco, F., Bardini, G., Mencucci, A., Ciani, S., Pierazzuoli, E., Tsuchihashil, K., Rigalleau, V., Delafaye, C., Baillet, L., Vergnot, V., Brunou, P., Gatta, B., Gin, H., Felber, J. P., Munger, R., Assimacopoulos, F., Bobbioni, E., Golay, A., Wilken, M., Larsen, F. S., Buckley, D., Molina, L. M., Marquez, L., Arbeo, A., Hernandez, C., Kofod, H., Damholt, A. B., Buchan, A., Márquez, L., Luque, M. A., Sarti, L., Sutton, P. J., Behle, K., Heimesaat, M. M., Hüfner, M., Gravholt, Claus Højbjerg, Mølier, Niels, Christiansen, Jens Sandahl, Schmitz, Ole, Deacon, C. F., Brock, B., Knudsen, L. B., Agersø, H., Huusfeldt, P. O., Kelly, C. M. N., Brunn, C., Schioos, J., Sewing, S., Lemansky, P., Wawro, S., Mest, H. J., Taguchi, T., Motoshima, H., Yoshizato, K., Guenifi, Amel, Henriksson, M., Johansson, J., Shafqat, J., Tally, M., Wahren, J., Jömvall, H., Ekberg, K., Rigler, R., Pramanik, A., Kratz, G., Johansson, B.-L., Uhlén, M., Jörnvall, H., Forst, T., Dufayet De La Tour, D., Kunt, T., Pfützner, A., Goitom, K., Pohlmann, T., Schneider, S., Johansson, B. L., Löbig, M., Engelbach, M., Beyer, J., Ekman, Bertil, Nyström, Fredrik, Arnqvist, Hans J., Halvatsiotis, P. G., Meek, S., Bigelow, M., Nair, K. S., Maghsoudi, S., Fisker, S., Vølund, A. A., Jörgensen, J. O. L., Christiansen, J. S., Hilsted, J., Mazerkina, N. A., Tiulpakov, A. N., Gorelyshev, S. K., Peterkova, V. A., Macut, D. J., Dieguez, C., Casanueva, F. F., Catalina, P. F., Mallo, F., Andrade, A., García-Mayor, R. V. G., Popova, V. V., ter Maaten, J. C., Popp-Snijders, C., Madsen, L., Ukropec, J., Bergene, E., Rnstan, A. C., Berge, R., Arner, P., Wahl, G., Häring, H., Bryson, J. M., Curtis, S. E., Caterson, I. D., Winzell, M. Sörhede, Svensson, H., Ahnén, B., Holm, C., Phillips, C., Madigan, C., Owens, D., Collins, P., Johnson, A., Tomkin, G. H., Cabezas, M. Castro, van Oostrom, A. J. H. H. M., Erkelens, D. W., Summers, L. K. M., Fielding, B. A., Ilic, V., Clark, M. L., Frayn, K. N., Pietzsch, J., Julius, U., Nitzsche, S., Fischer, S., Lindgren, C., Amrot-Fors, L., Hoffmann, M. M., Luft, D., Schmülling, R.-M., D’Adamo, M., Leonetti, F., Paoloni, A., Ribaudo, M. C., Basso, M. S., Elmore, U., Restuccia, A., Sbraccia, P., Emilsson, V., O’Dowd, J., Heyman, R., Cawthorne, M. A., Pelikánová, T., Kazdová, L., Žák, A., Chvojková, Š., Özer, E. M., Kadıoğlu, P., Korugan, Ü., Hatemi, H., Rivellese, A. A., Dullaart, R. P. F., Riemens, S. C., Sluiter, W. J., van Tol, A., Farnier, M., Megnien, S., Turpin, G., Stulp, B. K., Brambilla, P., Brunelli, A., Riva, M. C., Manzoni, P., de Poli, S., Riboni, S., Stolk, R. P., Meijer, R., Wink, O., Zelissen, P. M. J., van Gils, A. P. G., Grobbee, D. 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W., Taverna, M., Guerre-Millo, M., Chevalier, A., Pacher, N., Slama, G., Gorshunska, M., Buyken, A. E., Heitkamp, G., Kabir, M., Oppert, J. M., Wursch, P., Bruzzo, F., Rahman, M. H., Fatima, K., Ahmed, S., Mondal, H. N., Yilmaz, M., Öztok, U., Karakoç, A., Çakır, N., Düzgün, E., Yetkin, İ., Arslan, M., Şardaş, S., Wilding, John, Géloën, A., Baret, G., Dalmaz, Y., Peyronnet, J., Clémenceau, B., Martignat, L., Lalain, S., Gouin, E., Kenda-Ropson, N., Miller, A. O. A., You, S., Aguilera, E., Recasens, M., Flores, L., Ricart, M. J., Fernández-Cruz, L., Esmatjes, E., Crenier, L., Noël, C., Le Moine, A., Mahy, M., Danguy, A., Kiss, R., Goldman, M., Bracci, C., De Haan, B., Nilsson, K., Deschamps, J. Y., Glagoličová, A., Smrčková, I., Dieterle, C., Illner, W. D., Land, W., Feldmeier, H., Scheuer, R., Lalli, C., Di Loreto, C., Ellringmann, U., Balks, H. J., v. zur Mühlen, A., Dengler, R., Weissenborn, K., Rasmussen, B. M., Ørskov, L., Watson, J., Owen, G., Barrett, G., Ingleby, J., Weiss, M., Deary, I., Cavan, D., Kerr, D., Bruneiii, A., Cuce’, A., Elsing, H. G., Kühne, D., Quinn, N. D., Warner, D. P., Buysschaert, M., Jamal, R., O’Brien, T., Latare, P., Mullen, J., Rein, A., Wargo, M., Parkes, J. L., Ginsberg, B., Sotiropoulos, A., Peppas, Th. A., Kotsini, V., Apostolou, O., Bousboulas, S., Michailidis, E., Sawala, M., Pappas, S., Nilsson, P. M., Nilsson, J. Å., Berglund, G., Molins, T., Esteban, J. I., Genescà, J., Paris, I., Haufroid, V., Selvais, Ph., Petit, J. M., Duong, M., Grappin, M., Guiguet, M., Rudoni, S., Portier, H., Brun, J. M., Bagg, W., Plank, L., Drury, P. L., Sharpe, N., Braatvedt, G. D., Carrascosa, J. M., Molero, J. C., Fermίn, Y., Andrés, A., Satrústegui, J., Rietzsch, H., Patzak, A., Schwanebeck, U., Simpson, H., Robertson-Mackay, F., Montegriffo, E., Fox, C., Chiasson, J.-L., Josse, R. G., Dorman, J. M., Gerstein, H. C., Lau, D., Leiter, L. A., Maheux, P., Meneilly, G. S., Murphy, L., Rodger, N. W., Ross, S. A., Ryan, E., Yale, J.-F., Wolever, T. M. S., Haller, T., Elias, I., Segal, P., Standi, E., Rybka, J., Sencer, E., Satman, I., Schlcnzka, A., Vakkilainen, J., Tsaglis, H., Ioannidis, I., Giakoumaki, A., Amantou, A., Komitopoulos, N., Georgiou, S., Varsamis, E., Katsilambros, N., El Gayar, M., Shereba, N., Botros, R., Fikry, R., Jackson, D., Balme, M., Silva-Nunes, J., Alves, J., Bogalho, P., Gardete-Correia, L., Nunes-Corrêa, J., Kot’átková, A., Němcová, D., Vrbíková, J., Zamrazil, V., Meyer, L., Delbachian, I., Lehert, P., Cugnardey, N., Drouin, P., Guerci, B., Wagner, O. F., Jones, N. P., Vallance, S. E., Thompson, K. A., Miller, A. K., Inglis, A. M. L., Patterson, S., Jorkasky, D., Freed, M. I., Mathisen, A. L., Schneider, R., Rubin, C., Houser, V., Beebe, K. L., Kortboyer, J. M., Eckland, D. J. A., Cranmer, H., Mori, Y., Kurokawa, N., Komiya, H., Horikoshi, H., Yokoyama, J., Tajima, N., Ikeda, Y., Bakst, A., Hemyari, P., Lönnqvist, F., Owen, S., Vikramadithyan, R. K., Chakrabarti, R., Misra, P., Prem Kumar, M., Sunil Kumar, K. B., Ghosh, A., Rajagopalan, R., Goldstein, B., Katoh, S., Tsuruoka, N., Hata, S., Matsushima, M., Ikemoto, S., Inoue, Y., Edwards, G., Fonseca, V., Biswas, N., Bakris, G., Viberti, G., Rebuck, A. S., Weill, S., Abel, M. G., Klappoth, W., Brodesser, A., Linkeschowa, R., Pushparaj, P., Tan, C. H., Tan, B. K. H., Bahner, A., Parker, J., Waite, G., Lipson, V., Nahar, N., Rokeya, B., Parveen, S., Nur-e-Alam, M., Mosihuzzaman, M., Hansen, A. Kornerup, Lepore°, M., Kurzhals, R., Pampanelli°, S., Fanelli°, C. G., Bolli°, G. B., Ratner, R. E., Hirsch, I. B., Mecca, T. E., Wilson, C. A., Mohideen, P., Mudaliar, S., Deutsch, R., Ciaraldi, T., Armstrong, D., Kim, B., Morrill, B., Sha, X., Henry, R., Meyer, B. H., Scholtz, H. E., van Niekerk, N., Rosenkranz, B., Schoenle, E., Witthaus, Elke, Bradley, Clare, Stewart, John, Barbeau, M., Myers, S., Flora, D., DiMarchi, R., Chance, R., Plum, A., Larsen, P. S., Larsen, U. D., Kristensen, J. B., Jansen, J. A., Olsen, B., Mortensen, H., Hylleberg, B., Jacobsen, L. V., Gall, M.-A., Søgaard, B., Ewing, F. M., Ireland, R. H., Hoogwerf, B., Raskin, P., Jovanovic, L., Leiter, L., Boss, A. H., Bott, U., Ebrahim, S., Hirschberger, S., Leukel, P., Sieber, H. J., McGill, J., Kilo, C., Kamp, N. M., Wutte, A., Le Thai, F., Balarac, N., Allicar, M. P., Cazeneuve, B., Augendre, B., Wise, S. D., Seah, E. S., Koivisto, V., Torlone, E., Del Sindaco, P., Ciofetta, M., Hedman, C., Orre Pettersson, A.-C., Lindström, T., Cernigoi, A. M., Kong, N., Kitchen, M. M., Ryder, R. E. J., Petkova, M., Angelova-Gateva, P., Malone, J., Arora, V., Bue-Valleskey, J., Pein, M., Diebler, F., Roach, P., Gudat, U., Dreyer, M., Hanusch, U., Ristic, S., McLeod, J., Hirschberg, Y., Garreffa, S., Keilson, L., Mather, S., Gagen, K., Chen, W., Dragonas, N., Chuang, L. M., Juang, J. H., Wu, H. P., Chiang, Y. D., Li, K. L., Jorgensen, L. N., Tai, T. Y., Cheatham, W. W., Kennedy, F., Woo, V., Jain, R., Boss, A., Moses, R., Clauson, P., Fischer, T., Björk, S., Østergaard, A., Langendorf, K. W., Hatorp, V., Hasslacher, C., Farrar, N. S., Chambers, N. J., Denyer, G. S., Johnston, G. A. R., Hashiguchi, S., Jönsson, A., Hallengren, B., Rydberg, T., Herbaut, C., Turc, A., Mourand, I., Chevassus, H., Molinier, N., Christensen, A.-B. L., Mathiesen, E. R., Stage, E., Damm, P., Boivin, S., Gross, P., Pennington, M., Harder, T., Kohlhoff, R., Dörner, G., Rohde, W., Plagemann, A., Ferdeghini, M., Murru, S., Maffei, M., Cecchetti, P., Dunne, F., Brydon, P., Smith, T., Proffitt, M., Holder, R., Gee, H., Goulis, D. G., Teoh, T. G., Asatiani, N., Elphick, A., Natsvlishvili, M., Chanturia, T., Shelestova, E., Ramazashvili, M., Hod, M., Cederberg, J., Casi, A. Leunda, Pampfer, S., De Hertogh, R., Hinck, L., Aly, S., Bertie, J., Botta, R. M., Imbergamo, M. P., Impiccichè, M. G., Todaro, B., Greco, D., Ekbom, P., Clausen, P., Feldt-Rasmussen, U., Feldt-Rasmussen, B., Mølsted Pedersen, L., Nørgaard, K., Svenningsen, A., Nielsen, L., Zmudzińska, M., Ziętek, I., Min, Y., Crawford, M. A., Bozzoni, F., Corubolo, C., Borrello, E., Di Biase, N., Spagnolo, S., Hawthorne, G., Sen, D., Bagust, A., Maier, W., Currie, C. J., Sailesh, S., Patel, V., Hayes, D., Cockrill, B., Gatling, W., Budd, S., Mullee, M. A., Savill, A. W., Smithers, M. G., Davies, R. R., Sandford, A., Stutz, L., Vadstrup, S., Simonsen, V., Musaeus, L., Molsing, B., Lyholm, B., Turner, B. C., Jenkins, E., Hejlesen, O. J., Andreassen, S., Hovorka, R., Cavan, D. A., Klinge, A., Strauss, K. W., Guthrie, R., Testa, M., Zimmerman, R., Sandberg, M., Steinfatt, H., Hardenberg, R., Gottsmann, M., König, A., Schmauß, S., Hierl, F. X., Renders, C. M., Valk, G. D., van Eijk, J. Th. M., van der Wal, G., Jermendy, G., Hídvégi, T., Müller, U. A., Junghänel, J., Köhler, S., Köhler, C., Schumann, M., Use, G., de Valk, H. W., Blankestijn, J. G., de Bruin, H. J., Bottomley, J., Gillam, S., Holmes, J., Murphy, M., Madani, S. F., Müller, R., Hunger Dathe, W., Grüßer, M., Roien, D., Hussain, M., Vibe-Petersen, J., Braun, A., Schiel, R., Höfer, A., Leppert, K., Trento, M., Passera, P., Tomalino, M., Bajardi, M., Vaccari, P., Pagnozzi, F., Pomero, F., Molinatti, G. M., Porta, M., Blaauwwiekel, E. E., Hania, M., Scholten-Jaegers, S. M. H. J., Links, T. 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- Published
- 1999
- Full Text
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26. New developments in Krebs mixer-settler technology
- Author
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Sonntag, A., Szanto, I., and Goodman, D.
- Abstract
This paper presents the most recent developments in mixer-settler technology directed towards treating higher throughputs, increasing efficiencies and providing further improvement in SX technology with a new concept: the submerged launder. Industrial plants built in the last past few years and using these improvements are described.
- Published
- 1992
- Full Text
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27. Limit Cycles of a Cubic Kolmogorov System
- Author
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Lloyd, N. G., Pearson, J. M., Saez, E., and Szanto, I.
- Published
- 1996
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28. Activation of Deoxycytidine Kinase during Inhibition of DNA Synthesis by 2-Chloro-2'-Deoxyadenosine (Cladribine) in Human Lymphocytes
- Author
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Sasvari-Szekely, M., Spasokoukotskaja, T., Szoke, M., Csapo, Z., Turi, A., Szanto, I., Eriksson, S., and Staub, M.
- Published
- 1998
- Full Text
- View/download PDF
29. 35th Annual Meeting of the European Association for the Study of Diabetes : Brussels, Belgium, 28 September-2 October 1999
- Author
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Melander, A., Olsson, J., Lindberg, G., Salzman, A., Howard, T., Stang, P., Lydick, E., Emslie-Smith, A., Boyle, D. I. R., Evans, J. M. M., Macdonald, T. M., Bain, J., Sullivan, F., Ad Darts Memo, Morris For The Collaboration, Juhl, C., Porksen, N., Sturis, J., Hollingdal, M., Pincus, S., Veldhuis, J., Dejgaard, A., Schmitz, O., Kristensen, J. S., Frandsen, K. B., Bayer, Th, Muller, P., Dunning, B. E., Paladini, S., Gutierrez, C., Deacon, R., Valentin, M., Grunberger, G., Weston, W. M., Patwardhan, R., Rappaport, E. B., Sargeant, L. A., Wareham, N. J., Khaw, K. T., Zethelius, Bjorn, Lithell, Hans, Hales, C. Nicholas, Berne, Christian, Lakka, H-M, Oksanen, L., Tuomainen, T-P, Kontula, K., Salonen, J. T., Dekker, J. M., Boks, P., Vegt, F., Stehouwer, C. D. A., Nijpels, G., Bouter, L. M., Heine, R. J., Bruno, G., Cavallo-Perin, P., Bargero, G., D Errico, N., Borra, M., Macchia, G., Pagano, G., Newton, R. W., Ruta, D. A., New, J. P., Wallace, C., Roxburgh, M. A., Young, R. J., Vaughan, N. 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J., Quinones Galvan, A., Simeoni, M., Basu, A., Uosukainen, A., Makimattila, S., Schlenzka, A., Adler, A. I., Levy, J., Stevens, R., Matthews, D., Holman, R., Boland, B. J., Jeanjean, M., Hermans, M. P., Maudoigt, C., Tonglet, R., Robert, A., Cini, G., Galetta, F., Sanna, G., Gernone, F., Janssen, M. J., Gonera, R. K., Wolffenbuttel, B. H. R., Leeuw, P. W., Schaper, N. C., Moleda, P., Kuczerowski, R., Czech, A., Taton, J., Taddei, S., Patiag, D., Qu, X., Wilkes, M., Gray, S., Seale, J. P., Donnelly, R., Campion, J., Maestro, B., Davila, N., Carranza, M. C., Calle, C., Hales, C. N., Fernandez-Real, J. M., Grasa, M., Pugeat, M., Barret, C., Ricart, W., Lindmark, S., Olsson, T., Tufvesson, M., Loeblein, K., Mehnert, B., Haering, H. U., Rave, Klaus, Heise, Tim, Clauson, Per, Hirschberger, Sabine, Heinemann, Lutz, Claret, M., Nadal, B., Truc, A., Rossi, L., Hildebrand, P., Ketterer, S., Beglinger, C., Keller, U., Gyr, K., Parvin, S., Overkamp, D., Vayreda, M., Gonzalez-Huix, F., G-Huix, F., Zavaroni, I., Gasparini, P., Massironi, P., Zuccarelli, A., Delsignore, R., Reaven, G. M., Sheu, W. H. H., Lee, W. J., Chen, Y-T, Iraklianou, S., Tournis, S., Volonakis, I., Spylopoulou, M., Bilianou, E., Melidonis, A., Foussas, S., Guler, Serdar, Cakir, Bekir, Demi Rbas, Berrin, Gursoy, Gul, Serter, Rustu, Aral, Yalcin, Morton, G., Lee, S., Fahey, R., Silva, A., Cai, X. J., Buckingham, R. E., Arch, J. R. S., Wilson, S., Clausen, J. T., Kristensen, P., Nielsen, P. F., Wulff, B. S., Thim, L., Holness, M. J., Sugden, M. C., Fryer, L. G. D., Munns, M. 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J., Taguchi, T., Motoshima, H., Yoshizato, K., Guenifi, Amel, Henriksson, M., Johansson, J., Shafqat, J., Tally, M., Wahren, J., Jomvall, H., Ekberg, K., Rigler, R., Pramanik, A., Kratz, G., Johansson, B-L, Uhlen, M., Jornvall, H., Forst, T., Dufayet La Tour, D., Kunt, T., Pfutzner, A., Goitom, K., Pohlmann, T., Schneider, S., Johansson, B. L., Lobig, M., Engelbach, M., Beyer, J., Ekman, Bertil, Nystrom, Fredrik, Arnqvist, Hans J., Halvatsiotis, P. G., Meek, S., Bigelow, M., Nair, K. S., Maghsoudi, S., Fisker, S., Volund, A. A., Jorgensen, J. O. L., Christiansen, J. S., Hilsted, J., Mazerkina, N. A., Tiulpakov, A. N., Gorelyshev, S. K., Peterkova, V. A., Macut, D. J., Dieguez, C., Casanueva, F. F., Catalina, P. F., Mallo, F., Andrade, A., Garcia-Mayor, R. V. G., Popova, V. V., Ter Maaten, J. C., Popp-Snijders, C., Madsen, L., Ukropec, J., Bergene, E., Rnstan, A. C., Berge, R., Arner, P., Wahl, G., Haring, H., Bryson, J. M., Curtis, S. E., Caterson, I. D., Winzell, M. Sorhede, Svensson, H., Ahnen, B., Holm, C., Phillips, C., Madigan, C., Owens, D., Collins, P., Johnson, A., Tomkin, G. H., Cabezas, M. Castro, Oostrom, A. J. H. H. M., Erkelens, D. W., Summers, L. K. M., Fielding, B. A., Ilic, V., Clark, M. L., Frayn, K. N., Pietzsch, J., Julius, U., Nitzsche, S., Fischer, S., Lindgren, C., Amrot-Fors, L., Hoffmann, M. M., Luft, D., Schmulling, R-M, D Adamo, M., Leonetti, F., Paoloni, A., Ribaudo, M. C., Basso, M. S., Elmore, U., Restuccia, A., Sbraccia, P., Emilsson, V., O Dowd, J., Heyman, R., Cawthorne, M. A., Pelikanova, T., Kazdova, L., Zak, A., Chvojkova, S., Ozer, E. M., Kadioglu, P., Korugan, U., Hatemi, H., Rivellese, A. A., Dullaart, R. P. F., Riemens, S. C., Sluiter, W. J., Tol, A., Farnier, M., Megnien, S., Turpin, G., Cerivastatin Combination Therapy Study Group, Stulp, B. K., Brambilla, P., Brunelli, A., Riva, M. C., Manzoni, P., Poli, S., Riboni, S., Stolk, R. P., Meijer, R., Wink, O., Zelissen, P. M. J., Gils, A. P. G., Grobbee, D. 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W., Taverna, M., Guerre-Millo, M., Chevalier, A., Pacher, N., Slama, G., Gorshunska, M., Buyken, A. E., Heitkamp, G., Kabir, M., Oppert, J. M., Wursch, P., Bruzzo, F., Rahman, M. H., Fatima, K., Ahmed, S., Mondal, H. N., Yilmaz, M., Oztok, U., Karakoc, A., Cakir, N., Duzgun, E., Yetkin, I., Arslan, M., Sardas, S., Wilding, John, Geloen, A., Baret, G., Dalmaz, Y., Peyronnet, J., Clemenceau, B., Martignat, L., Lalain, S., Gouin, E., Kenda-Ropson, N., Miller, A. O. A., You, S., Aguilera, E., Recasens, M., Flores, L., Ricart, M. J., Fernandez-Cruz, L., Esmatjes, E., Crenier, L., Noel, C., Le Moine, A., Mahy, M., Danguy, A., Kiss, R., Goldman, M., Bracci, C., Haan, B., Nilsson, K., Deschamps, J. Y., Glagolicova, A., Smrckova, I., Dieterle, C., Illner, W. D., Land, W., Feldmeier, H., Scheuer, R., Lalli, C., Di Loreto, C., Ellringmann, U., Balks, H. J., V Zur Muhlen, A., Dengler, R., Weissenborn, K., Rasmussen, B. M., Orskov, L., Watson, J., Owen, G., Barrett, G., Ingleby, J., Weiss, M., Deary, I., Cavan, D., Kerr, D., Bruneiii, A., Cuce, A., Elsing, H. G., Kuhne, D., Quinn, N. D., Warner, D. P., Buysschaert, M., Jamal, R., O Brien, T., Latare, P., Mullen, J., Rein, A., Wargo, M., Parkes, J. L., Ginsberg, B., Sotiropoulos, A., Peppas, Th A., Kotsini, V., Apostolou, O., Bousboulas, S., Michailidis, E., Sawala, M., Pappas, S., Nilsson, P. M., Nilsson, J. A., Berglund, G., Molins, T., Esteban, J. I., Genesca, J., Paris, I., Haufroid, V., Selvais, Ph, Petit, J. M., Duong, M., Grappin, M., Guiguet, M., Rudoni, S., Portier, H., Brun, J. M., Bagg, W., Plank, L., Drury, P. L., Sharpe, N., Braatvedt, G. D., Carrascosa, J. M., Molero, J. C., Fermίn, Y., Andres, A., Satrustegui, J., Rietzsch, H., Patzak, A., Schwanebeck, U., Simpson, H., Robertson-Mackay, F., Montegriffo, E., Fox, C., Chiasson, J-L, Josse, R. G., Dorman, J. M., Gerstein, H. C., Lau, D., Leiter, L. A., Maheux, P., Meneilly, G. 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A., Cranmer, H., Mori, Y., Kurokawa, N., Komiya, H., Horikoshi, H., Yokoyama, J., Tajima, N., Ikeda, Y., Bakst, A., Hemyari, P., Lonnqvist, F., Owen, S., Vikramadithyan, R. K., Chakrabarti, R., Misra, P., Prem Kumar, M., Sunil Kumar, K. B., Ghosh, A., Rajagopalan, R., Goldstein, B., Katoh, S., Tsuruoka, N., Hata, S., Matsushima, M., Ikemoto, S., Inoue, Y., Edwards, G., Fonseca, V., Biswas, N., Bakris, G., Viberti, G., Rebuck, A. S., Weill, S., Abel, M. G., Klappoth, W., Brodesser, A., Linkeschowa, R., Pushparaj, P., Tan, C. H., Tan, B. K. H., Bahner, A., Parker, J., Waite, G., Lipson, V., Nahar, N., Rokeya, B., Parveen, S., Nur-E-Alam, M., Mosihuzzaman, M., Hansen, A. Kornerup, Kurzhals, R., Ratner, R. E., Hirsch, I. B., Mecca, T. E., Wilson, C. A., Mohideen, P., Mudaliar, S., Deutsch, R., Ciaraldi, T., Armstrong, D., Kim, B., Morrill, B., Sha, X., Henry, R., Meyer, B. H., Scholtz, H. E., Niekerk, N., Rosenkranz, B., Schoenle, E., Hoe, Study Group, Witthaus, Elke, Bradley, Clare, Stewart, John, Barbeau, M., Myers, S., Flora, D., Dimarchi, R., Chance, R., Plum, A., Larsen, P. S., Larsen, U. D., Kristensen, J. B., Jansen, J. A., Olsen, B., Mortensen, H., Hylleberg, B., Jacobsen, L. V., Gall, M-A, Sogaard, B., Ewing, F. M., Ireland, R. H., Hoogwerf, B., Raskin, P., Jovanovic, L., Leiter, L., Boss, A. H., Bott, U., Ebrahim, S., Hirschberger, S., Leukel, P., Sieber, H. J., Mcgill, J., Kilo, C., Kamp, N. M., Wutte, A., Le Thai, F., Balarac, N., Allicar, M. P., Cazeneuve, B., Augendre, B., Wise, S. D., Seah, E. S., Koivisto, V., Torlone, E., Del Sindaco, P., Ciofetta, M., Hedman, C., Orre Pettersson, A-C, Lindstrom, T., Cernigoi, A. M., Kong, N., Kitchen, M. M., Ryder, R. E. 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30. Application of the krebs solvent extraction system to copper hydrometallurgy.
- Author
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Kohler K.C., Extraction metallurgy 85 London 09-Sep-8512-Sep-85, Sonntag A.A., Szanto I., Kohler K.C., Extraction metallurgy 85 London 09-Sep-8512-Sep-85, Sonntag A.A., and Szanto I.
31. New developments in KREBS mixer settler technology.
- Author
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Sonntag A.A., Goodman D.A., Szanto I., Sonntag A.A., Goodman D.A., and Szanto I.
- Abstract
The most recent developments in KREBS technology directed towards treating higher throughputs, increasing efficiencies and providing further improvement in SX technology with a new concept, the submerged launder, are presented., The most recent developments in KREBS technology directed towards treating higher throughputs, increasing efficiencies and providing further improvement in SX technology with a new concept, the submerged launder, are presented.
32. On the construction of certain Dulac functions
- Author
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Saez, E., primary and Szanto, I., additional
- Published
- 1988
- Full Text
- View/download PDF
33. Investigation of calcitonin (CT) binding to its receptors (CTR) in MCF-7 human breast cancer cell line
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Vincze, B., Lőrincz, I., Pályi, I., Kerpel-Fronius, S., Számel, I., Szántó, I., Svastics, E., and Sugár, J.
- Published
- 1987
- Full Text
- View/download PDF
34. THE ROLE OF VARIABLE PARAMETERS IN THE CONTINUOUS X-RAY DIFFRACTION ANALYSIS OF STRUCTURAL CHANGE PHENOMENA
- Author
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Szanto, I
- Published
- 1965
35. NADPH oxidases in healthy white adipose tissue and in obesity: function, regulation, and clinical implications.
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Jornayvaz FR, Gariani K, Somm E, Jaquet V, Bouzakri K, and Szanto I
- Subjects
- Humans, Animals, Insulin Resistance, Oxidation-Reduction, Mice, Diabetes Mellitus, Type 2 metabolism, Adipocytes metabolism, Obesity metabolism, NADPH Oxidases metabolism, Adipose Tissue, White metabolism, Reactive Oxygen Species metabolism
- Abstract
Reactive oxygen species, when produced in a controlled manner, are physiological modulators of healthy white adipose tissue (WAT) expansion and metabolic function. By contrast, unbridled production of oxidants is associated with pathological WAT expansion and the establishment of metabolic dysfunctions, most notably insulin resistance and type 2 diabetes mellitus. NADPH oxidases (NOXs) produce oxidants in an orderly fashion and are present in adipocytes and in other diverse WAT-constituent cell types. Recent studies have established several links between aberrant NOX-derived oxidant production, adiposity, and metabolic homeostasis. The objective of this review is to highlight the physiological roles attributed to diverse NOX isoforms in healthy WAT and summarize current knowledge of the metabolic consequences related to perturbations in their adequate oxidant production. We detail WAT-related alterations in preclinical investigations conducted in NOX-deficient murine models. In addition, we review clinical studies that have employed NOX inhibitors and currently available data related to human NOX mutations in metabolic disturbances. Future investigations aimed at understanding the integration of NOX-derived oxidants in the regulation of the WAT cellular redox network are essential for designing successful redox-related precision therapies to curb obesity and attenuate obesity-associated metabolic pathologies., (© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)
- Published
- 2024
- Full Text
- View/download PDF
36. Case report: Initial atypical skeletal symptoms and dental anomalies as first signs of Gardner syndrome: the importance of genetic analysis in the early diagnosis.
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Antal G, Zsigmond A, Till Á, Orsi E, Szanto I, Büki G, Kereskai L, Herbert Z, Hadzsiev K, and Bene J
- Subjects
- Humans, Female, Adolescent, Tooth Abnormalities genetics, Tooth Abnormalities pathology, Tooth Abnormalities diagnosis, Early Diagnosis, Pedigree, Gardner Syndrome genetics, Gardner Syndrome diagnosis, Gardner Syndrome pathology, Genetic Testing
- Abstract
Background: Gardner syndrome is a rare genetic cancer predisposition disorder characterized by intestinal polyposis, multiple osteomas, and soft and hard tissue tumors. Dental anomalies are present in approximately 30%-70% of patients with Gardner syndrome and can be discovered during routine dental examinations. However, sometimes the diagnosis is challenging due to the high clinical variability and incomplete clinical picture. Herein, we report a family with various dental and bone anomalies, in which the definitive diagnosis was established with the help of a comprehensive genetic analysis based on state-of-the-art next-generation sequencing technology. Case presentation: A 17-year-old female index patient presented with dental (caries, impacted, retained and anteriorly located teeth) and atypical bone anomalies not resembling Gardner syndrome. She was first referred to our Genetic Counselling Unit at the age of 11 due to an atypical bone abnormality identified by a panoramic X-ray. Tooth 3.6 was surgically removed and the histopathology report revealed a Paget's disease-like bone metabolic disorder with mixed osteoblastic and osteoclastic activity of the mandible. A small lumbar subcutaneous tumor was discovered by physical examination. Ultrasound examination of the tumor raised the possibility of a soft tissue propagation of chondromatosis. Her sister, 2 years younger at the age of 14, had some benign tumors (multiple exostoses, odontomas, epidermoid cysts) and impacted teeth. Their mother had also skeletal symptoms. Her lower teeth did not develop, the 9th-10th ribs were fused, and she complained of intermittent jaw pain. A cranial CT scan showed fibrous dysplasia on the cranial bones. Whole exome sequencing identified a heterozygous pathogenic nonsense mutation (c.4700C>G; p.Ser1567*) in the APC gene in the index patient's DNA. Targeted sequencing revealed the same variant in the DNA of the other affected family members (the sister and the mother). Conclusion: Early diagnosis of this rare, genetically determined syndrome is very important, because of the potentially high malignant transformation of intestinal polyps. Dentists should be familiar with the typical maxillofacial features of this disorder, to be able to refer patients to genetic counseling. Dental anomalies often precede the intestinal polyposis and facilitate the early diagnosis, thereby increasing the patients' chances of survival. Genetic analysis may be necessary in patients with atypical phenotypic signs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Antal, Zsigmond, Till, Orsi, Szanto, Büki, Kereskai, Herbert, Hadzsiev and Bene.)
- Published
- 2024
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37. Non-pain-related complaints of paediatric patients after dental treatment under general anaesthesia.
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Radacsi A, Sandor B, Farkas N, Kovesi T, Szanto I, and Katona K
- Subjects
- Child, Humans, Child Behavior, Dental Care, Anesthesia, General adverse effects, Anesthesia, Dental adverse effects
- Abstract
Aim: To investigate the prevalence, duration, and severity of non-pain-related complaints after dental treatment under general anaesthesia (DTGA) and to identify correlating factors from patient's characteristics and treatment., Methods: Parents/caregivers of children treated under general anaesthesia were asked to fill in a dichotomous questionnaire during hospitalisation and the postoperative week. Several complaints were evaluated in relation to factors associated with dental treatment and general anaesthesia., Conclusion: Postoperative morbidity after DTGA is common. Patients and their parents should be informed about the possibility of experiencing mild to moderate complaints, and adverse events that may last up to 7 days.
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- 2023
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38. Pain-related complaints of paediatric patients after dental treatment under general anaesthesia.
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Radacsi A, Katona K, Farkas N, Kovesi T, Szanto I, and Sandor B
- Subjects
- Humans, Child, Cross-Sectional Studies, Anesthesia, Local, Dental Care, Pain, Postoperative, Anesthesia, General adverse effects
- Abstract
Aim: To identify factors related to postoperative pain and to recognise strategies to reduce this pain after dental treatment under general anaesthesia., Methods: Cross-sectional observational study. Children treated under general ansesthesia reported pain daily using the Wong Baker FACES® Pain Rating Scale. Their parents/caregivers filled in a related Yes/No questionnaire during hospitalisation and the first postoperative week. The duration and severity of pain were evaluated in relation to various factors., Conclusion: A well-established protocol is indicated to reduce operation time. Patients and their parents should be informed about the possibility of constantly subsiding postoperative pain that may last for a week. As additional local anaesthesia during general anaesthesia (GA) does not provide postoperative pain reduction in deciduous tooth extraction cases, its administration could be omitted.
- Published
- 2023
- Full Text
- View/download PDF
39. NADPH Oxidases Connecting Fatty Liver Disease, Insulin Resistance and Type 2 Diabetes: Current Knowledge and Therapeutic Outlook.
- Author
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Nascè A, Gariani K, Jornayvaz FR, and Szanto I
- Abstract
Nonalcoholic fatty liver disease (NAFLD), characterized by ectopic fat accumulation in hepatocytes, is closely linked to insulin resistance and is the most frequent complication of type 2 diabetes mellitus (T2DM). One of the features connecting NAFLD, insulin resistance and T2DM is cellular oxidative stress. Oxidative stress refers to a redox imbalance due to an inequity between the capacity of production and the elimination of reactive oxygen species (ROS). One of the major cellular ROS sources is NADPH oxidase enzymes (NOX-es). In physiological conditions, NOX-es produce ROS purposefully in a timely and spatially regulated manner and are crucial regulators of various cellular events linked to metabolism, receptor signal transmission, proliferation and apoptosis. In contrast, dysregulated NOX-derived ROS production is related to the onset of diverse pathologies. This review provides a synopsis of current knowledge concerning NOX enzymes as connective elements between NAFLD, insulin resistance and T2DM and weighs their potential relevance as pharmacological targets to alleviate fatty liver disease.
- Published
- 2022
- Full Text
- View/download PDF
40. NADPH Oxidase 4 (NOX4) in Cancer: Linking Redox Signals to Oncogenic Metabolic Adaptation.
- Author
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Szanto I
- Subjects
- Humans, Hypoxia, NADPH Oxidase 1 metabolism, NADPH Oxidase 4 genetics, NADPH Oxidase 4 metabolism, Oxidation-Reduction, Reactive Oxygen Species metabolism, NADPH Oxidases metabolism, Neoplasms
- Abstract
Cancer cells can survive and maintain their high proliferation rate in spite of their hypoxic environment by deploying a variety of adaptative mechanisms, one of them being the reorientation of cellular metabolism. A key aspect of this metabolic rewiring is the promotion of the synthesis of antioxidant molecules in order to counter-balance the hypoxia-related elevation of reactive oxygen species (ROS) production and thus combat the onset of cellular oxidative stress. However, opposite to their negative role in the inception of oxidative stress, ROS are also key modulatory components of physiological cellular metabolism. One of the major physiological cellular ROS sources is the NADPH oxidase enzymes (NOX-es). Indeed, NOX-es produce ROS in a tightly regulated manner and control a variety of cellular processes. By contrast, pathologically elevated and unbridled NOX-derived ROS production is linked to diverse cancerogenic processes. In this respect, NOX4, one of the members of the NOX family enzymes, is of particular interest. In fact, NOX4 is closely linked to hypoxia-related signaling and is a regulator of diverse metabolic processes. Furthermore, NOX4 expression and function are altered in a variety of malignancies. The aim of this review is to provide a synopsis of our current knowledge concerning NOX4-related processes in the oncogenic metabolic adaptation of cancer cells.
- Published
- 2022
- Full Text
- View/download PDF
41. Course induced dexterity development and cerebellar grey matter growth of dentistry students: a randomised trial.
- Author
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Siman B, Janszky J, Perlaki G, Fazekas A, Sandor B, Katona K, Marada G, and Szanto I
- Subjects
- Adolescent, Adult, Clinical Competence, Female, Humans, Longitudinal Studies, Male, Students, Young Adult, Dentistry, Gray Matter physiology, Motor Skills, Psychomotor Performance
- Abstract
This study primarily focuses on the assessment of dentistry students' improvement of manual skills resulting from their participation in courses. We aimed to prove that systematic manual skills development significantly improves dexterity. We hypothesized that the dexterity training regimen improves manual dexterity demonstrated by the HAM-Man (Hamburg Assessment Test for Medicine-Manual Dexterity) test scores and CGM (cerebellar grey matter) growth. Thirty volunteers were randomly divided into two equal groups (study and control). Firstly, volunteers were examined by the HAM-Man test and baseline MRI scans. Afterwards, a manual skills development course was launched for the "study group". Secondly, all the manual skills of the students were evaluated longitudinally, by the HAM-Man test. Simultaneously, the follow-up MRI scans were taken to observe morphologic changes in the cerebellum. The Wilcoxon signed-rank test and Student Paired t-test were used for statistical analyses. Value p < 0.05 was considered significant. After the training, significant growth of CGM as well as improvement on manual skill assessment tests, were found in the study group. Training courses are suitable for preparing students with low levels of dexterity for performing demanding tasks. The improvement is demonstrable by a wire bending test and by bilateral CGM enlargement as well.
- Published
- 2021
- Full Text
- View/download PDF
42. Beta-Cell-Specific Expression of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 5 Aggravates High-Fat Diet-Induced Impairment of Islet Insulin Secretion in Mice.
- Author
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Bouzakri K, Veyrat-Durebex C, Holterman C, Arous C, Barbieux C, Bosco D, Altirriba J, Alibashe M, Tournier BB, Gunton JE, Mouche S, Bietiger W, Forterre A, Berney T, Pinget M, Christofori G, Kennedy C, and Szanto I
- Subjects
- Animals, Cells, Cultured, Diet, High-Fat adverse effects, Female, Humans, Insulin Secretion drug effects, Male, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, NADPH Oxidase 5 metabolism, Islets of Langerhans metabolism, NADPH Oxidase 5 genetics
- Abstract
Aims: Nicotinamide adenine dinucleotide phosphate oxidases (NOX-es) produce reactive oxygen species and modulate β-cell insulin secretion. Islets of type 2 diabetic subjects present elevated expression of NOX5. Here, we sought to characterize regulation of NOX5 expression in human islets in vitro and to uncover the relevance of NOX5 in islet function in vivo using a novel mouse model expressing NOX5 in doxycycline-inducible, β-cell-specific manner (RIP/rtTA/NOX5 mice). Results: In situ hybridization and immunohistochemistry employed on pancreatic sections demonstrated NOX5 messenger ribonucleic acid (mRNA) and protein expressions in human islets. In cultures of dispersed islets, NOX5 protein was observed in somatostatin-positive (δ) cells in basal (2.8 m M glucose) conditions. Small interfering ribonucleic acid (siRNA)-mediated knockdown of NOX5 in human islets cultured in basal glucose concentrations resulted in diminished glucose-induced insulin secretion (GIIS) in vitro . However, when islets were preincubated in high (16.7 m M ) glucose media for 12 h, NOX5 appeared also in insulin-positive (β) cells. In vivo , mice with β-cell NOX5 expression developed aggravated impairment of GIIS compared with control mice when challenged with 14 weeks of high-fat diet. Similarly, in vitro palmitate preincubation resulted in more severe reduction of insulin release in islets of RIP/rtTA/NOX5 mice compared with their control littermates. Decreased insulin secretion was most distinct in response to theophylline stimulation, suggesting impaired cyclic adenosine monophosphate (cAMP)-mediated signaling due to increased phosphodiesterase activation. Innovation and Conclusions: Our data provide the first insight into the complex regulation and function of NOX5 in islets implying an important role for NOX5 in δ-cell-mediated intraislet crosstalk in physiological circumstances but also identifying it as an aggravating factor in β-cell failure in diabetic conditions.
- Published
- 2020
- Full Text
- View/download PDF
43. H 2 O 2 Metabolism in Normal Thyroid Cells and in Thyroid Tumorigenesis: Focus on NADPH Oxidases.
- Author
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Szanto I, Pusztaszeri M, and Mavromati M
- Abstract
Thyroid hormone synthesis requires adequate hydrogen peroxide (H
2 O2 ) production that is utilized as an oxidative agent during the synthesis of thyroxin (T4) and triiodothyronine (T3). Thyroid H2 O2 is generated by a member of the family of NADPH oxidase enzymes (NOX-es), termed dual oxidase 2 (DUOX2). NOX/DUOX enzymes produce reactive oxygen species (ROS) as their unique enzymatic activity in a timely and spatially regulated manner and therefore, are important regulators of diverse physiological processes. By contrast, dysfunctional NOX/DUOX-derived ROS production is associated with pathological conditions. Inappropriate DUOX2-generated H2 O2 production results in thyroid hypofunction in rodent models. Recent studies also indicate that ROS improperly released by NOX4, another member of the NOX family, are involved in thyroid carcinogenesis. This review focuses on the current knowledge concerning the redox regulation of thyroid hormonogenesis and cancer development with a specific emphasis on the NOX and DUOX enzymes in these processes.- Published
- 2019
- Full Text
- View/download PDF
44. Comparison of fractionation strategies for offline two-dimensional liquid chromatography tandem mass spectrometry analysis of proteins from mouse adipose tissue.
- Author
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Sajic T, Varesio E, Szanto I, and Hopfgartner G
- Subjects
- Animals, Male, Mice, Adipose Tissue metabolism, Chromatography, Liquid methods, Proteomics methods, Tandem Mass Spectrometry methods
- Abstract
In the frame of protein identification from mouse adipose tissue, two strategies were compared for the offline elution of peptides from a strong cation exchange (SCX) column in two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS/MS) analyses. First, the salt gradient (using K(+) as displacing agent) was evaluated from 25 to 500mM KCl. Then, a less investigated elution mode using a pH gradient (using citric acid and ammonium hydroxide) was carried out from pH 2.5 to 9.0. Equal amounts of peptide digest derived from mouse adipose tissue were loaded onto the SCX column and fractionated according to the two approaches. A total of 15 fractions were collected in two independent experiments for each SCX elution strategy. Then, each fraction was analyzed on a nanoLC-MS/MS platform equipped with a column-switching unit for desalting and enrichment. No substantial differences in peptide quality characteristics (molecular weight, isoelectric point, or GRAVY [grand average of hydropathicity] index distributions) were observed between the two datasets. The pH gradient approach was found to be superior, with 27.5% more unique peptide identifications and 10% more distinct protein identifications compared with the salt-based elution method. In conclusion, our data imply that the pH gradient SCX fractionation is more desirable for proteomics analysis of entire adipose tissue., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
45. NADPH oxidase 4 deficiency reduces aquaporin-2 mRNA expression in cultured renal collecting duct principal cells via increased PDE3 and PDE4 activity.
- Author
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Féraille E, Dizin E, Roth I, Derouette JP, Szanto I, Martin PY, de Seigneux S, and Hasler U
- Subjects
- 1-Methyl-3-isobutylxanthine, Animals, Aquaporin 2 genetics, Arginine Vasopressin metabolism, Blotting, Western, Cyclic AMP metabolism, Kidney Tubules, Collecting cytology, Mice, NADPH Oxidase 4, Quinolones, RNA, Messenger genetics, RNA, Small Interfering genetics, Real-Time Polymerase Chain Reaction, Rolipram, Signal Transduction physiology, Aquaporin 2 metabolism, Cyclic Nucleotide Phosphodiesterases, Type 3 metabolism, Cyclic Nucleotide Phosphodiesterases, Type 4 metabolism, NADPH Oxidases deficiency, RNA, Messenger metabolism, Reactive Oxygen Species metabolism
- Abstract
The final control of renal water reabsorption occurs in the collecting duct (CD) and relies on regulated expression of aquaporin-2 (AQP2) in principal CD cells. AQP2 transcription is primarily induced by type 2 vasopressin receptor (V2R)-cAMP-protein kinase A (PKA) signaling but also by other factors, including TonEBP and NF-κB. NAPDH oxidase 4 (NOX4) represents a major source of reactive oxygen species (ROS) in the kidney. Because NOX-derived ROS may alter PKA, TonEBP and NF-κB activity, we examined the effects of NOX4 depletion on AQP2 expression. Depleted NOX4 expression by siRNA (siNOX4) in mpkCCDcl4 cells attenuated increased AQP2 mRNA expression by arginine vasopressin (AVP) but not by hypertonicity, which induces both TonEBP and NF-κB activity. AVP-induced AQP2 expression was similarly decreased by the flavoprotein inhibitor diphenyleneiodonium. siNOX4 altered neither TonEBP nor NF-κB activity but attenuated AVP-inducible cellular cAMP concentration, PKA activity and CREB phosphorylation as well as AQP2 mRNA expression induced by forskolin, a potent activator of adenylate cyclase. The repressive effect of siNOX4 on AVP-induced AQP2 mRNA expression was abolished by the non-selective phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX) and was significantly decreased by selective PDE antagonists cilostamide and rolipram, but not vinpocetine, which respectively target PDE3, PDE4 and PDE1. Thus, by inhibiting PDE3 and PDE4 activity NOX4-derived ROS may contribute to V2R-cAMP-PKA signaling and enhance AQP2 transcription.
- Published
- 2014
- Full Text
- View/download PDF
46. STAT6 promotes bi-directional modulation of PKM2 in liver and adipose inflammatory cells in rosiglitazone-treated mice.
- Author
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Sajic T, Hainard A, Scherl A, Wohlwend A, Negro F, Sanchez JC, and Szanto I
- Subjects
- Adipose Tissue cytology, Adipose Tissue drug effects, Animals, Liver cytology, Liver drug effects, Mice, Mice, Knockout, Rosiglitazone, Signal Transduction drug effects, Thyroid Hormone-Binding Proteins, Adipose Tissue metabolism, Carrier Proteins metabolism, Liver metabolism, Membrane Proteins metabolism, Proteome metabolism, STAT6 Transcription Factor metabolism, Signal Transduction physiology, Thiazolidinediones pharmacology, Thyroid Hormones metabolism
- Abstract
STAT6 interacts with PPARγ to elicit macrophage polarization towards an anti-inflammatory, insulin-sensitizing phenotype. Mice deficient in STAT6 display liver lipid accumulation (hepatosteatosis). Rosiglitazone (RSG), a PPARγ agonist, ameliorates hepatosteatosis and enhances insulin sensitivity. To elucidate the role of STAT6 in PPARγ action on hepatosteatosis we compared liver proteomes of RSG-treated wild type and STAT6-deficient mice and we identified pyruvate kinase M2 (PKM2), a glycolysis and proliferation-regulating enzyme that displayed STAT6-dependent expression. RSG induced PKM2 within inflammatory cells in liver but suppressed its expression in adipose tissue. RSG diminished hepatosteatosis and oxidative stress, enhanced fat accumulation and improved insulin sensitivity in STAT6-deficient mice. Our data reveal a complex interaction between STAT6 and PPARγ in the regulation of liver and adipose tissue lipid depot distribution and design STAT6 as a novel link between inflammatory cell metabolism and adipocyte and hepatocyte function.
- Published
- 2013
- Full Text
- View/download PDF
47. NADPH-oxidase 4 protects against kidney fibrosis during chronic renal injury.
- Author
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Nlandu Khodo S, Dizin E, Sossauer G, Szanto I, Martin PY, Feraille E, Krause KH, and de Seigneux S
- Subjects
- Animals, Antioxidants metabolism, Apoptosis, Atrophy, Capillaries pathology, Fibrosis, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Kidney Diseases genetics, Kidney Diseases pathology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, NADPH Oxidase 2, NADPH Oxidase 4, NF-E2-Related Factor 2 metabolism, Oxidative Stress, Ureteral Obstruction, Vascular Endothelial Growth Factor A metabolism, Kidney pathology, Kidney Diseases enzymology, Membrane Glycoproteins metabolism, NADPH Oxidases metabolism
- Abstract
NADPH oxidases synthesize reactive oxygen species that may participate in fibrosis progression. NOX4 and NOX2 are NADPH oxidases expressed in the kidneys, with the former being the major renal isoform, but their contribution to renal disease is not well understood. Here, we used the unilateral urinary obstruction model of chronic renal injury to decipher the role of these enzymes using wild-type, NOX4-, NOX2-, and NOX4/NOX2-deficient mice. Compared with wild-type mice, NOX4-deficient mice exhibited more interstitial fibrosis and tubular apoptosis after obstruction, with lower interstitial capillary density and reduced expression of hypoxia-inducible factor-1α and vascular endothelial growth factor in obstructed kidneys. Furthermore, NOX4-deficient kidneys exhibited increased oxidative stress. With NOX4 deficiency, renal expression of other NOX isoforms was not altered but NRF2 protein expression was reduced under both basal and obstructed conditions. Concomitant deficiency of NOX2 did not modify the phenotype exhibited by NOX4-deficient mice after obstruction. NOX4 silencing in a mouse collecting duct (mCCD(cl1)) cell line increased TGF-β1-induced apoptosis and decreased NRF2 protein along with expression of its target genes. In addition, NOX4 silencing decreased hypoxia-inducible factor-1α and expression of its target genes in response to hypoxia. In summary, these results demonstrate that the absence of NOX4 promotes kidney fibrosis, independent of NOX2, through enhanced tubular cell apoptosis, decreased microvascularization, and enhanced oxidative stress. Thus, NOX4 is crucial for the survival of kidney tubular cells under injurious conditions.
- Published
- 2012
- Full Text
- View/download PDF
48. Comparison of three detergent-free protein extraction protocols for white adipose tissue.
- Author
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Sajic T, Hopfgartner G, Szanto I, and Varesio E
- Subjects
- Animals, Blotting, Western methods, Chloroform chemistry, Detergents chemistry, Male, Methanol chemistry, Mice, Proteins chemistry, Sucrose chemistry, Trifluoroethanol chemistry, Water chemistry, Adipose Tissue, White metabolism, Centrifugation methods, Chemical Fractionation methods, Proteins isolation & purification
- Abstract
A comparative study of three detergent-free protein extraction protocols--a differential centrifugal fractionation, a delipidation protocol based on the Bligh and Dyer method, and the trifluoroethanol addition as cosolvent to an aqueous buffer--was performed on white adipose tissue. The performance of the protocols directly compatible with liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was evaluated based on the total protein extraction yield and the protein recovery from different functional and cellular compartments. The most suitable method for the extraction of white adipose tissue proteins from a wide range of cellular and structural compartments was the delipidation protocol based on the Bligh and Dyer method., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
49. Differential proteomic analysis of STAT6 knockout mice reveals new regulatory function in liver lipid homeostasis.
- Author
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Iff J, Wang W, Sajic T, Oudry N, Gueneau E, Hopfgartner G, Varesio E, and Szanto I
- Subjects
- Animals, Computer Simulation, Fatty Acid-Binding Proteins genetics, Fatty Acid-Binding Proteins metabolism, Female, Gene Expression, Heat-Shock Proteins, Immunohistochemistry, Isotope Labeling, Male, Mass Spectrometry methods, Mice, Mice, Inbred BALB C, Mice, Knockout, Promoter Regions, Genetic, Proteome metabolism, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, STAT6 Transcription Factor genetics, Signal Transduction, Suppressor of Cytokine Signaling 3 Protein, Suppressor of Cytokine Signaling Proteins genetics, Suppressor of Cytokine Signaling Proteins metabolism, Lipid Metabolism physiology, Liver metabolism, Proteomics methods, STAT6 Transcription Factor metabolism
- Abstract
Increased inflammatory signaling is a key feature of metabolic disorders. In this context, the role of increased pro-inflammatory signals has been extensively studied. By contrast, no efforts have been dedicated to study the contrasting scenario: the attenuation of anti-inflammatory signals and their role in metabolic homeostasis. IL-4 and IL-13 are anti-inflammatory cytokines signaling through the Signal Transducer and Activator of Transcription 6 (STAT6). Our study was aimed at evaluating the lack of STAT6 signaling on liver homeostasis. To this end we analyzed the liver proteome of wild type and STAT6 knock-out mice using 2D nanoscale LC-MS/MS with iTRAQ labeling technique. The coordinated changes in proteins identified by this quantitative proteome analysis indicated disturbed lipid homeostasis and a state of hepatocellular stress. Most significantly, the expression of the liver fatty acid binding protein (FABP1) was increased in the knock-out mice. In line with the elevated FABP1 expression we found latent liver lipid accumulation in the STAT6-deficient mice which was further aggravated when mice were challenged by a high fat diet. In conclusion, our study revealed a so far uncharacterized role for STAT6 in regulating liver lipid homeostasis and demonstrates the importance of anti-inflammatory signaling in the defense against the development of liver steatosis.
- Published
- 2009
- Full Text
- View/download PDF
50. The central melanocortin system directly controls peripheral lipid metabolism.
- Author
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Nogueiras R, Wiedmer P, Perez-Tilve D, Veyrat-Durebex C, Keogh JM, Sutton GM, Pfluger PT, Castaneda TR, Neschen S, Hofmann SM, Howles PN, Morgan DA, Benoit SC, Szanto I, Schrott B, Schürmann A, Joost HG, Hammond C, Hui DY, Woods SC, Rahmouni K, Butler AA, Farooqi IS, O'Rahilly S, Rohner-Jeanrenaud F, and Tschöp MH
- Subjects
- Adipocytes cytology, Adipocytes metabolism, Adipose Tissue cytology, Adipose Tissue metabolism, Animals, Behavior, Animal physiology, Eating, Glucose metabolism, Humans, Insulin metabolism, Melanocyte-Stimulating Hormones administration & dosage, Melanocyte-Stimulating Hormones metabolism, Mice, Mice, Knockout, Rats, Rats, Sprague-Dawley, Receptor, Melanocortin, Type 4 genetics, Receptor, Melanocortin, Type 4 metabolism, Receptors, Melanocortin, alpha-MSH administration & dosage, alpha-MSH analogs & derivatives, alpha-MSH metabolism, Central Nervous System metabolism, Lipid Metabolism, Melanocortins metabolism, Signal Transduction physiology
- Abstract
Disruptions of the melanocortin signaling system have been linked to obesity. We investigated a possible role of the central nervous melanocortin system (CNS-Mcr) in the control of adiposity through effects on nutrient partitioning and cellular lipid metabolism independent of nutrient intake. We report that pharmacological inhibition of melanocortin receptors (Mcr) in rats and genetic disruption of Mc4r in mice directly and potently promoted lipid uptake, triglyceride synthesis, and fat accumulation in white adipose tissue (WAT), while increased CNS-Mcr signaling triggered lipid mobilization. These effects were independent of food intake and preceded changes in adiposity. In addition, decreased CNS-Mcr signaling promoted increased insulin sensitivity and glucose uptake in WAT while decreasing glucose utilization in muscle and brown adipose tissue. Such CNS control of peripheral nutrient partitioning depended on sympathetic nervous system function and was enhanced by synergistic effects on liver triglyceride synthesis. Our findings offer an explanation for enhanced adiposity resulting from decreased melanocortin signaling, even in the absence of hyperphagia, and are consistent with feeding-independent changes in substrate utilization as reflected by respiratory quotient, which is increased with chronic Mcr blockade in rodents and in humans with loss-of-function mutations in MC4R. We also reveal molecular underpinnings for direct control of the CNS-Mcr over lipid metabolism. These results suggest ways to design more efficient pharmacological methods for controlling adiposity.
- Published
- 2007
- Full Text
- View/download PDF
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