Browsing by Author "Gonzalez, Daniel R."

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    Coordinated Endothelial Nitric Oxide Synthase Activation by Translocation and Phosphorylation Determines Flow-Induced Nitric Oxide Production in Resistance Vessels
    (2013) Figueroa, Xavier F.; Gonzalez, Daniel R.; Puebla, Mariela; Acevedo, Juan P.; Rojas-Libano, Daniel; Duran, Walter N.; Boric, Mauricio P.
    Background/Aims: Endothelial nitric oxide synthase (eNOS) is associated with caveolin-1 (Cav-1) in plasma membrane. We tested the hypothesis that eNOS activation by shear stress in resistance vessels depends on synchronized phosphorylation, dissociation from Cav-1 and translocation of the membrane-bound enzyme to Golgi and cytosol. Methods: In isolated, perfused rat arterial mesenteric beds, we evaluated the effect of changes in flow rate (2-10 ml/min) on nitric oxide (NO) production, eNOS phosphorylation at serine 1177, eNOS subcellular distribution and co-immunoprecipitation with Cav-1, in the presence or absence of extracellular Ca2+. Results: Increases in flow induced a biphasic rise in NO production: a rapid transient phase (3-5-min) that peaked during the first 15 s, followed by a sustained phase, which lasted until the end of stimulation. Concomitantly, flow caused a rapid translocation of eNOS from the microsomal compartment to the cytosol and Golgi, paralleled by an increase in eNOS phosphorylation and a reduction in eNOS-Cav-1 association. Transient NO production, eNOS translocation and dissociation from Cav-1 depended on extracellular Ca2+, while sustained NO production was abolished by the PI3K-Akt blocker wortmannin. Conclusions: In intact resistance vessels, changes in flow induce NO production by transient Ca2+-dependent eNOS translocation from membrane to intracellular compartments and sustained Ca2+-independent PI3K-Akt-mediated phosphorylation. (C) 2013 S. Karger AG, Basel
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    Differential role of S-nitrosylation and the NO-cGMP-PKG pathway in cardiac contractility
    (2008) Gonzalez, Daniel R.; Fernandez, Ignacio C.; Ordenes, Pablo P.; Treuer, Adriana V.; Eller, Gisela; Boric, Mauricio P.
    The role of nitric oxide (NO) in cardiac contractility is complex and controversial. Several NO donors have been reported to cause positive or negative inotropism. NO can bind to guanylate cyclase, increasing cGMP production and activating PKG. NO may also directly S-nitrosylate cysteine residues of specific proteins. We used the isolated rat heart preparation to test the hypothesis that the differential inotropic effects depend on the degree of NO production and the signaling recruited. SNAP (S-nitroso-N-acetylpenicillamine), a NO donor, increased contractility at 0.1, 1 and 10 M. This effect was independent of phospholamban phosphorylation, was not affected by PKA inhibition with H-89 (N-[2((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide), but it was abolished by the radical scavenger Tempol (4-hydroxy-[2,2,4,4]-tetramethyl-piperidine-1-oxyl). However, at 100 mu M SNAP reduced contractility, effect reversed to positive inotropism by guanylyl cyclase blockade with ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), and abolished by PKG inhibition with KT5823, but not affected by Tempol. SNAP increased tissue cGMP at 100 M, but not at lower concentrations. Consistently, a cGMP analog also reduced cardiac contractility. Finally, SNAP at 1 mu M increased the level of S-nitrosylation of various cardiac proteins, including the ryanodine receptor. This study demonstrates the biphasic role for NO in cardiac contractility in a given preparation; furthermore, the differential effect is clearly ascribed to the signaling pathways involved. We conclude that although NO is highly diffusible, its output determines the fate of the messenger: low NO concentrations activate redox processes (S-nitrosylation), increasing con-tractility;while the cGMP-PKG pathway is activated at high NO concentrations, reducing contractility. (c) 2007 Elsevier Inc. All rights reserved.
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    Inhibition of human topoisomerase I and activation of caspase-3 by aza-angucyclinones and arylaminopyrimido[4,5-c]isoquinoline-7,10-quinones
    (SPANDIDOS PUBL LTD, 2012) Monsalve, Francisco A.; Valderrama, Jaime A.; Vasquez, David; Ibacache, Andrea; Rodriguez, Jaime A.; Gonzalez, Daniel R.; Leiva, Elba; Gonzalez, Enrique
    Cancer is the second cause of death in the world after cardiovascular diseases. Cancer cells acquire capacities not present in normal cells, such as self-sufficiency, resistance to antiproliferative stimuli, evasion of apoptosis, unlimited replication, invasiveness and metastasis. Consequently, it is of major interest to explore and develop molecules with anticancer activity directed to specific targets. In this study, we aimed to evaluate two series of polycyclic quinones: aza-angucyclinone and arylaminopyrimido[4,5-c]isoquinoline-7,10-quinones, in their capacity to inhibit human topoisomerase I (TOP1) and to trigger apoptosis through activation of caspase-3. We evaluated the capacity of the two series of polycyclic quinones to inhibit TOP1, using a DNA supercoiled relaxation assay and their capacity to induce apoptosis through the activation of caspase-3 in HL60 cells. Both series of quinones inhibited TOP1 activity over 50%. When we evaluated the pro-apoptotic capacity of both series of quinones, at therapeutically relevant concentrations, the arylaminoquinones ADPA-ICC (methyl 7-(4-methoxyphenyl)amino-1,3-dimethyl-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylate), P4 (9-phenylamino-3,4-dihydrophenanthridine-1,7,10(2H)-trione) and the aza-angucyclinone OH-6H (8-hydroxy-2,4-dimethyl-2H,4H-benzo[g]pyrimido[4,5-c]isoquinoline-1,3,7,12-tetraone) increased the caspase-3 activity by approximately 2-fold over the control. The series of the arylaminoquinones and aza-angucyclinones showed differential antiproliferative capacity. We further identified a group of them that showed antiproliferative capacity possibly through inhibition of TOP1 and by activation of caspase-3. This group of molecules may represent a potential pharmacological tool in treatment against cancer.
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    New NADPH Oxidase 2 Inhibitors Display Potent Activity against Oxidative Stress by Targeting p22phox-p47phox Interactions
    (2023) Treuer, Adriana V.; Faundez, Mario; Ebensperger, Roberto; Hovelmeyer, Erwin; Vergara-Jaque, Ariela; Perera-Sardina, Yunier; Gutierrez, Margarita; Fuentealba, Roberto; Gonzalez, Daniel R.
    NADPH oxidase (NOX2) is responsible for reactive oxygen species (ROS) production in neutrophils and has been recognized as a key mediator in inflammatory and cardiovascular pathologies. Nevertheless, there is a lack of specific NOX2 pharmacological inhibitors. In medicinal chemistry, heterocyclic compounds are essential scaffolds for drug design, and among them, indole is a very versatile pharmacophore. We tested the hypothesis that indole heteroaryl-acrylonitrile derivatives may serve as NOX2 inhibitors by evaluating the capacity of 19 of these molecules to inhibit NOX2-derived ROS production in human neutrophils (HL-60 cells). Of these compounds, C6 and C14 exhibited concentration-dependent inhibition of NOX2 (IC50-1 mu M). These molecules also reduced NOX2-derived oxidative stress in cardiomyocytes and prevented cardiac damage induced by ischemia-reperfusion. Compound C6 significantly reduced the membrane translocation of p47(phox), a cytosolic subunit that is required for NOX2 activation. Molecular docking analyses of the binding modes of these molecules with p47(phox) indicated that C6 and C14 interact with specific residues in the inner part of the groove of p47(phox), the binding cavity for p22(phox). This combination of methods showed that novel indole heteroaryl acrylonitriles represent interesting lead compounds for developing specific and potent NOX2 inhibitors.
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    Outcomes of Patients Presenting with Mild Acute Respiratory Distress Syndrome Insights from the LUNG SAFE Study
    (2019) Tai Pham; Neto, Ary Serpa; Pelosi, Paolo; Laffey, John Gerard; De Haro, Candelaria; Angel Lorente, Jose; Bellani, Giacomo; Fan, Eddy; Brochard, Laurent Jean; Pesenti, Antonio; Schultz, Marcus Josephus; Artigas, Antonio; Esteban, Andres; Gattinoni, Luciano; van Haren, Frank; Larsson, Anders; McAuley, Daniel F.; Ranieri, Marco; Rubenfeld, Gordon; Thompson, B. Taylor; Wrigge, Hermann; Slutsky, Arthur S.; Rios, Fernando; Sottiaux, Thierry; Depuydt, Pieter; Lora, Fredy S.; Azevedo, Luciano Cesar; Bugedo, Guillermo; Qiu, Haibo; Gonzalez, Marcos; Silesky, Juan; Cerny, Vladimir; Nielsen, Jonas; Jibaja, Manuel; Matamis, Dimitrios; Luis Ranero, Jorge; Amin, Pravin; Hashemian, S. M.; Clarkson, Kevin; Kurahashi, Kiyoyasu; Villagomez, Asisclo; Zeggwagh, Amine Ali; Heunks, Leo M.; Laake, Jon Henrik; Emmanuel Palo, Jose; Fernandes, Antero do Vale; Sandesc, Dorel; Arabi, Yaasen; Bumbasierevic, Vesna; Nin, Nicolas; Piquilloud, Lise; Abroug, Fekri; McNamee, Lia; Hurtado, Javier; Bajwa, Ed; Dempaire, Gabriel; Sula, Hektor; Nunci, Lordian; Cani, Alma; Zazu, Alan; Dellera, Christian; Insaurralde, Carolina S.; Alejandro, Risso, V; Daldin, Julio; Vinzio, Mauricio; Fernandez, Ruben O.; Cardonnet, Luis P.; Bettini, Lisandro R.; Carboni Bisso, Mariano; Osman, Emilio M.; Setten, Mariano G.; Lovazzano, Pablo; Alvarez, Javier; Villar, Veronica; Pozo, Norberto C.; Grubissich, Nicolas; Plotnikow, Gustavo A.; Vasquez, Daniela N.; Ilutovich, Santiago; Tiribelli, Norberto; Chena, Ariel; Pellegrini, Carlos A.; Saenz, Maria G.; Estenssoro, Elisa; Brizuela, Matias; Gianinetto, Hernan; Gomez, Pablo E.; Cerrato, Valeria, I; Bezzi, Marco G.; Borello, Silvina A.; Loiacono, Flavia A.; Fernandez, Adriana M.; Knowles, Serena; Reynolds, Claire; Inskip, Deborah M.; Miller, Jennene J.; Kong, Jing; Whitehead, Christina; Bihari, Shailesh; Seven, Aylin; Krstevski, Amanda; Rodgers, Helen J.; Millar, Rebecca T.; Mckenna, Toni E.; Bailey, Irene M.; Hanlon, Gabrielle C.; Aneman, Anders; Lynch, Joan M.; Azad, Raman; Neal, John; Woods, Paul W.; Roberts, Brigit L.; Kol, Mark R.; Wong, Helen S.; Riss, Katharina C.; Staudinger, Thomas; Wittebole, Xavier; Berghe, Caroline; Bulpa, Pierre A.; Dive, Alain M.; Verstraete, Rik; Lebbinck, Herve; Vermassen, Joris; Meersseman, Philippe; Ceunen, Helga; Rosa, Jonas, I; Beraldo, Daniel O.; Piras, Claudio; Rampinelli, Adenilton M.; Nassar Jr, Antonio P.; Mataloun, Sergio; Moock, Marcelo; Thompson, Marlus M.; Goncalves, Claudio H.; Antonio, Ana Carolina P.; Ascoli, Aline; Biondi, Rodrigo S.; Fontenele, Danielle C.; Nobrega, Danielle; Sales, Vanessa M.; Abul Wahab, Ahmad Yazid Bin H. J.; Ismail, Maizatul; Shindhe, Suresh; Beloncle, Francois; Davies, Kyle G.; Cirone, Rob; Manoharan, Venika; Ismail, Mehvish; Goligher, Ewan C.; Jassal, Mandeep; Nishikawa, Erin; Javeed, Areej; Curley, Gerard; Rittayamai, Nuttapol; Parotto, Matteo; Ferguson, Niall D.; Mehta, Sangeeta; Knoll, Jenny; Pronovost, Antoine; Canestrini, Sergio; Bruhn, Alejandro R.; Garcia, Patricio H.; Aliaga, Felipe A.; Farias, Pamela A.; Yumha, Jacob S.; Ortiz, Claudia A.; Salas, Javier E.; Saez, Alejandro A.; Vega, Luis D.; Labarca, Eduardo F.; Martinez, Felipe T.; Carreno, Nicolas G.; Lora, Pilar; Liu, Haitao; Liu, Ling; Tang, Rui; Luo, Xiaoming; An, Youzhong; Zhao, Huiying; Gao, Yan; Zhai, Zhe; Ye, Zheng L.; Wang, Wei; Li, Wenwen; Li, Qingdong; Zheng, Ruiqiang; Yu, Wenkui; Shen, Juanhong; Li, Xinyu; Yu, Tao; Lu, Weihua; Wu, Ya Q.; Huang, Xiao B.; He, Zhenyang; Lu, Yuanhua; Han, Hui; Zhang, Fan; Sun, Renhua; Wang, Hua X.; Qin, Shu H.; Zhu, Bao H.; Zhao, Jun; Liu, Jian; Li, Bin; Liu, Jing L.; Zhou, Fa C.; Li, Qiong J.; Zhang, Xing Y.; Zhou Li-Xin; Qiang Xin-Hua; Jiang, Liangyan; Gao, Yuan N.; Zhao, Xian Y.; Li, Yuan Y.; Li, Xiao L.; Wang, Chunting; Yao, Qingchun; Yu, Rongguo; Chen, Kai; Shao, Huanzhang; Qin, Bingyu; Huang, Qing Q.; Zhu, Wei H.; Hang, Ai Y.; Hua, Ma X.; Li, Yimin; Xu, Yonghao; Di, Yu D.; Ling, Long L.; Qin, Tie H.; Wang, Shou H.; Qin, Junping; Han, Yi; Zhou, Suming; Vargas, Monica P.; Silesky Jimenez, Juan, I; Gonzalez Rojas, Manuel A.; Solis-Quesada, Jaime E.; Ramirez-Alfaro, Christian M.; Maca, Jan; Sklienka, Peter; Gjedsted, Jakob; Christiansen, Aage; Villamagua, Boris G.; Llano, Miguel; Burtin, Philippe; Buzancais, Gautier; Beuret, Pascal; Pelletier, Nicolas; Mortaza, Satar; Mercat, Alain; Chelly, Jonathan; Jochmans, Sebastien; Terzi, Nicolas; Daubin, Cedric; Carteaux, Guillaume; de Prost, Nicolas; Chiche, Jean-Daniel; Daviaud, Fabrice; Fartoukh, Muriel; Barberet, Guillaume; Biehler, Jerome; Dellamonica, Jean; Doyen, Denis; Arnal, Jean-Michel; Briquet, Anais; Hraiech, Sami; Papazian, Laurent; Follin, Arnaud; Roux, Damien; Messika, Jonathan; Kalaitzis, Evangelos; Dangers, Laurence; Combes, Alain; Au, Siu-Ming; Beduneau, Gaetan; Carpentier, Dorothee; Zogheib, Elie H.; Dupont, Herve; Ricome, Sylvie; Santoli, Francesco L.; Besset, Sebastien L.; Michel, Philippe; Gelee, Bruno; Danin, Pierre-Eric; Goubaux, Bernard; Crova, Philippe J.; Phan, Nga T.; Berkelmans, Frantz; Badie, Julio C.; Tapponnier, Romain; Gally, Josette; Khebbeb, Samy; Herbrecht, Jean-Etienne; Schneider, Francis; Declercq, Pierre-Louis M.; Rigaud, Jean-Philippe; Duranteau, Jacques; Harrois, Anatole; Chabanne, Russell; Marin, Julien; Bigot, Charlene; Thibault, Sandrine; Ghazi, Mohammed; Boukhazna, Messabi; Zein, Salem Ould; Richecoeur, Jack R.; Combaux, Daniele M.; Grelon, Fabien; Le Moal, Charlene; Sauvadet, Elise P.; Robine, Adrien; Lemiale, Virginie; Reuter, Danielle; Dres, Martin; Demoule, Alexandre; Goldgran-Toledano, Dany; Baboi, Loredana; Guerin, Claude; Lohner, Ralph; Krassler, Jens; Schaefer, Susanne; Zacharowski, Kai D.; Meybohm, Patrick; Reske, Andreas W.; Simon, Philipp; Hopf, Hans-Bernd F.; Schuetz, Michael; Baltus, Thomas; Papanikolaou, Metaxia N.; Papavasilopoulou, Theonymfi G.; Zacharas, Giannis A.; Ourailogloy, Vasilis; Mouloudi, Eleni K.; Massa, Eleni, V; Nagy, Eva O.; Stamou, Electra E.; Kiourtzieva, Ellada, V; Oikonomou, Marina A.; Avila, Luis E.; Cortez, Cesar A.; Citalan, Johanna E.; Jog, Sameer A.; Sable, Safal D.; Shah, Bhagyesh; Gurjar, Mohan; Baronia, Arvind K.; Memon, Mohammedfaruk; Muthuchellappan, Radhakrishnan; Ramesh, Venkatapura J.; Shenoy, Anitha; Unnikrishnan, Ramesh; Dixit, Subhal B.; Rhayakar, Rachana, V; Ramakrishnan, Nagarajan; Bhardwaj, Vallish K.; Mahto, Heera L.; Sagar, Sudha, V; Palaniswamy, Vijayanand; Ganesan, Deeban; Jamaati, Hamidreza; Heidari, Farshad; Meaney, Edel A.; Nichol, Alistair; Knapman, Karl M.; O'Croinin, Donall; Dunne, Eimhin S.; Breen, Dorothy M.; Jaafar, Rola F.; Dwyer, Rory; Amir, Fahd; Ajetunmobi, Olaitan O.; O'Muircheartaigh, Aogan C.; Black, Colin S.; Treanor, Nuala; Collins, Daniel, V; Altaf, Wahid; Zani, Gianluca; Fusari, Maurizio; Spadaro, Savino; Volta, Carlo A.; Graziani, Romano; Brunettini, Barbara; Palmese, Salvatore; Formenti, Paolo; Umbrello, Michele; Lombardo, Andrea; Pecci, Elisabetta; Botteri, Marco; Savioli, Monica; Protti, Alessandro; Mattei, Alessia; Schiavoni, Lorenzo; Tinnirello, Andrea; Todeschini, Manuel; Giarratano, Antonino; Cortegiani, Andrea; Sher, Sara; Rossi, Anna; Antonelli, Massimo M.; Montini, Luca M.; Casalena, Paolo; Scafetti, Sergio; Panarello, Giovanna; Occhipinti, Giovanna; Patroniti, Nicolo; Pozzi, Matteo; Biscione, Roberto R.; Poli, Michela M.; Raimondi, Ferdinando; Albiero, Daniela; Crapelli, Giulia; Beck, Eduardo; Pota, Vincenzo; Schiavone, Vincenzo; Molin, Alexandre; Tarantino, Fabio; Monti, Giacomo; Frati, Elena; Mirabella, Lucia; Cinnella, Gilda; Fossali, Tommaso; Colombo, Riccardo; Pattarino, Pierpaolo Terragni Ilaria; Mojoli, Francesco; Braschi, Antonio; Borotto, Erika E.; Cracchiolo, Andrea N.; Palma, Daniela M.; Raponi, Francesco; Foti, Giuseppe; Vascotto, Ettore R.; Coppadoro, Andrea; Brazzi, Luca; Floris, Leda; Iotti, Giorgio A.; Venti, Aaron; Yamaguchi, Osamu; Takagi, Shunsuke; Maeyama, Hiroki N.; Watanabe, Eizo; Yamaji, Yoshihiro; Shimizu, Kazuyoshi; Shiozaki, Kyoko; Futami, Satoru; Ryosuke, Sekine; Saito, Koji; Kameyama, Yoshinobu; Ueno, Keiko; Izawa, Masayo; Okuda, Nao; Suzuki, Hiroyuki; Harasawa, Tomofumi; Nasu, Michitaka; Takada, Tadaaki; Ito, Fumihito; Nunomiya, Shin; Koyama, Kansuke; Abe, Toshikazu; Andoh, Kohkichi; Kusumoto, Kohei; Hirata, Akira; Takaba, Akihiro; Kimura, Hiroyasu; Matsumoto, Shuhei; Higashijima, Ushio; Honda, Hiroyuki; Aoki, Nobumasa; Imai, Hiroshi; Ogino, Yasuaki; Mizuguchi, Ichiko; Ichikado, Kazuya; Nitta, Kenichi; Mochizuki, Katsunori; Hashida, Tomoaki; Tanaka, Hiroyuki; Nakamura, Tomoyuki; Niimi, Daisuke; Ueda, Takeshi; Kashiwa, Yozo; Uchiyama, Akinori; Sabelnikovs, Olegs; Oss, Peteris; Haddad, Youssef; Liew, Kong Y.; Namendys-Silva, Silvio A.; Jarquin-Badiola, Yves D.; Sanchez-Hurtado, Luis A.; Gomez-Flores, Saira S.; Marin, Maria C.; Lemus, Jordana S.; Fierro, Jonathan M.; Ramirez Cervantes, Mavy; Flores Mejia, Francisco Javier; Dector, Dulce; Rojas, Alejandro; Gonzalez, Daniel R.; Estrella, Claudia R.; Sanchez-Medina, Jorge R.; Ramirez-Gutierrez, Alvaro; George, Fernando G.; Aguirre, Janet S.; Buensuseso, Juan A.; Poblano, Manuel; Dendane, Tarek; Balkhi, Hicham; Elkhayari, Mina; Samkaoui, Nacer; Ezzouine, Hanane; Benslama, Abdellatif; Amor, Mourad; Maazouzi, Wajdi; Cimic, Nedim; Beck, Oliver; Bruns, Monique M.; Schouten, Jeroen A.; Rinia, Myra; Raaijmakers, Monique; Van Wezel, Hellen M.; Heines, Serge J.; Strauch, Ulrich; Buise, Marc P.; Simonis, Fabienne D.; Goodson, Jennifer C.; Browne, Troy S.; Navarra, Leanlove; Hunt, Anna; Hutchison, Robyn A.; Bailey, Mathew B.; Newby, Lynette; McArthur, Colin; Kalkoff, Michael; Mcleod, Alex; Casement, Jonathan; Hacking, Danielle J.; Andersen, Finn H.; Dolva, Merete S.; Barratt-Due, Andreas; Noremark, Kim Andre L.; Soreide, Eldar; Sjobo, Brit A.; Guttormsen, Anne B.; Leon Yoshido, Hector H.; Zumaran Aguilar, Ronald; Montes Oscanoa, Fredy A.; Alisasis, Alain U.; Robles, Joanne B.; Pasanting-Lim, Rossini Abbie B.; Tan, Beatriz C.; Andruszkiewicz, Pawel; Jakubowska, Karina; Coxo, Cristina M.; Alvarez, Antonio M.; Oliveira, Bruno S.; Montanha, Gustavo M.; Barros, Nelson C.; Pereira, Carlos S.; Messias, Antonio M.; Monteiro, Jorge M.; Araujo, Ana M.; Catorze, Nuno T.; Marum, Susan M.; Bouw, Maria J.; Gomes, Rui M.; Brito, Vania A.; Castro, Silvia; Estilita, Joana M.; Barros, Filipa M.; Serra, Isabel M.; Martinho, Aurelia M.; Tomescu, Dana R.; Marcu, Alexandra; Bedreag, Ovidiu H.; Papurica, Marius; Corneci, Dan E.; Negoita, Silvius Ioan; Grigoriev, Evgeny; Gritsan, Alexey, I; Gazenkampf, Andrey A.; Almekhlafi, Ghaleb; Albarrak, Mohamad M.; Mustafa, Ghanem M.; Maghrabi, Khalid A.; Salahuddin, Nawal; Aisa, Tharwat M.; Al Jabbary, Ahmed S.; Tabhan, Edgardo; Trinidad, Olivia A.; Al Dorzi, Hasan M.; Bolon, Stefan; Smith, Oliver; Mancebo, Jordi; Aguirre-Bermeo, Hernan; Lopez-Delgado, Juan C.; Esteve, Francisco; Rialp, Gemma; Forteza, Catalina; Albaiceta, Guillermo M.; De Cima-Iglesias, Sara; Seoane-Quiroga, Leticia; Ceniceros-Barros, Alexandra; Ruiz-Aguilar, Antonio L.; Claraco-Vega, Luis M.; Alfonso Soler, Juan; del Carmen Lorente, Maria; Hermosa, Cecilia; Gordo, Federico; Prieto-Gonzalez, Miryam; Lopez-Messa, Juan B.; Perez, Manuel P.; Perez, Cesar P.; Montoiro Allue, Raquel; Roche-Campo, Ferran; Ibanez-Santacruz, Marcos; Temprano, Susana; Pintado, Maria C.; De Pablo, Raul; Aroa Gomez, Pilar Ricart; Rodriguez Ruiz, Silvia; Iglesias Moles, Silvia; Teresa Jurado, Ma; Arizmendi, Alfons; Piacentini, Enrique A.; Franco, Nieves; Honrubia, Teresa; Perez Cheng, Meisy; Perez Losada, Elena; Blanco, Javier; Yuste, Luis J.; Carbayo-Gorriz, Cecilia; Cazorla-Barranquero, Francisca G.; Alonso, Javier G.; Alda, Rosa S.; Algaba, Angela; Navarro, Gonzalo; Cereijo, Enrique; Diaz-Rodriguez, Esther; Pastor Marcos, Diego; Alvarez Montero, Laura; Herrera Para, Luis; Jimenez Sanchez, Roberto; Blasco Navalpotro, Miguel Angel; Diaz Abad, Ricardo; Montiel Gonzalez, Raquel; Parrilla Toribio, Dacil; Castro, Alejandro G.; Artiga, Maria Jose D.; Penuelas, Oscar; Roser, Tomas P.; Olga, Moreno F.; Gallego Curto, Elena; Manzano Sanchez, Rocio; Imma, Vallverdu P.; Elisabet, Garcia M.; Claverias, Laura; Magret, Monica; Pellicer, Ana M.; Rodriguez, Lucia L.; Sanchez-Ballesteros, Jesus; Gonzalez-Salamanca, Angela; Jimenez, Antonio G.; Huerta, Francisco P.; Sotillo Diaz, Juan Carlos J.; Bermejo Lopez, Esther; Llinares Moya, David D.; Tallet Alfonso, Alec A.; Eugenio Luis, Palazon Sanchez; Sanchez Cesar, Palazon; Rafael, Sanchez, I; Virgilio, Corcoles G.; Recio, Noelia N.; Adamsson, Richard O.; Rylander, Christian C.; Holzgraefe, Bernhard; Broman, Lars M.; Wessbergh, Joanna; Persson, Linnea; Schioler, Fredrik; Kedelv, Hans; Tibblin, Anna Oscarsson; Appelberg, Henrik; Hedlund, Lars; Helleberg, Johan; Eriksson, Karin E.; Glietsch, Rita; Larsson, Niklas; Nygren, Ingela; Nunes, Silvia L.; Morin, Anna-Karin; Kander, Thomas; Adolfsson, Anne; Zender, Herve O.; Leemann-Refondini, Corinne; Elatrous, Souheil; Bouchoucha, Slaheddine; Chouchene, Imed; Ouanes, Islem; Ben Souissi, Asma; Kamoun, Salma; Demirkiran, Oktay; Aker, Mustafa; Erbabacan, Emre; Ceylan, Ilkay; Girgin, Nermin Kelebek; Ozcelik, Menekse; Unal, Necmettin; Meco, Basak Ceyda; Akyol, Onat O.; Derman, Suleyman S.; Kennedy, Barry; Parhar, Ken; Srinivasa, Latha; Hopkins, Phil; Mellis, Clare; Kakar, Vivek; Hadfield, Dan; Vercueil, Andre; Humphreys, Sally K.; Ferguson, Andrew; Mckee, Raymond; Raj, Ashok S.; Fawkes, Danielle A.; Watt, Philip; Twohey, Linda; Jha, Rajeev R.; Thomas, Matthew; Morton, Alex; Kadaba, Varsha; Smith, Mark J.; Hormis, Anil P.; Kannan, Santhana G.; Namih, Miriam; Reschreiter, Henrik; Camsooksai, Julie; Kumar, Alek; Rugonfalvi, Szabolcs; Nutt, Christopher; Oneill, Orla; Seasman, Colette; Dempsey, Ged; Scott, Christopher J.; Ellis, Helen E.; Mckechnie, Stuart; Hutton, Paula J.; Di Tomasso, Nora N.; Vitale, Michela N.; Griffin, Ruth O.; Dean, Michael N.; Cranshaw, Julius H.; Willett, Emma L.; Ioannou, Nicholas; Gillis, Sarah; Csabi, Peter; Macfadyen, Rosaleen; Dawson, Heidi; Preez, Pieter D.; Williams, Alexandra J.; Boyd, Owen; de Gordoa, Laura Ortiz-Ruiz; Bramall, Jon; Symmonds, Sophie; Chau, Simon K.; Wenham, Tim; Szakmany, Tamas; Toth-Tarsoly, Piroska; Mccalman, Katie H.; Alexander, Peter; Stephenson, Lorraine; Collyer, Thomas; Chapman, Rhiannon; Cooper, Raphael; Allan, Russell M.; Sim, Malcolm; Wrathall, David W.; Irvine, Donald A.; Zantua, Kim S.; Adams, John C.; Burtenshaw, Andrew J.; Sellors, Gareth P.; Welters, Ingeborg D.; Williams, Karen E.; Hessell, Robert J.; Oldroyd, Matthew G.; Battle, Ceri E.; Pillai, Suresh; Kajtor, Istvan; Sivashanmugavel, Mageswaran; Okane, Sinead C.; Donnelly, Adrian; Frigyik, Aniko D.; Careless, Jon P.; May, Martin M.; Stewart, Richard; Trinder, T. John; Hagan, Samantha J.; Cole, Jade M.; MacFie, Caroline C.; Dowling, Anna T.; Bhowmick, Kaushik; Nunez, Edgardo; Pittini, Gustavo; Rodriguez, Ruben; Imperio, Maria C.; Santos, Cristina; Franca, Ana G.; Ebeid, Alejandro; Deicas, Alberto; Serra, Carolina; Uppalapati, Aditya; Kamel, Ghassan; Banner-Goodspeed, Valerie M.; Beitler, Jeremy R.; Mukkera, Satyanarayana Reddy; Kulkarni, Shreedhar; Lee, Jarone; Mesar, Tomaz; Shinn, John O., III; Gomaa, Dina; Tainter, Christopher; Yeatts, Dale J.; Warren, Jessica; Lanspa, Michael J.; Miller, Russel R.; Grissom, Colin K.; Brown, Samuel M.; Bauer, Philippe R.; Gosselin, Ryan J.; Kitch, Barrett T.; Cohen, Jason E.; Beegle, Scott H.; Choudry, Shazia; Gueret, Renaud M.; Tulaimat, Aiman; Stigler, William; Batra, Hitesh; Huff, Nidhi G.; Lamb, Keith D.; Oetting, Trevor W.; Mohr, Nicholas M.; Judy, Claine; Saito, Shigeki; Kheir, Fayez; Schlichting, Adam B.; Delsing, Angela; Crouch, Daniel R.; Elmasri, Mary; Ismail, Dina; Dreyer, Kyle R.; Blakeman, Thomas C.; Baron, Rebecca M.; Grijalba, Carolina Quintana; Hou, Peter C.; Seethala, Raghu; Aisiku, Imo; Henderson, Galen; Frendl, Gyorgy; Hou, Sen-Kuang; Owens, Robert L.; Schomer, Ashley; Bumbasirevic, Vesna; Jovanovic, Bojan; Surbatovic, Maja; Veljovic, Milic
    Background: Patients with initial mild acute respiratory distress syndrome are often underrecognized and mistakenly considered to have low disease severity and favorable outcomes. They represent a relatively poorly characterized population that was only classified as having acute respiratory distress syndrome in the most recent definition. Our primary objective was to describe the natural course and the factors associated with worsening and mortality in this population.