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1. INTERBLEED: Design of an International Study of Risk Factors for Gastrointestinal Bleeding and Cardiovascular Events After Gastrointestinal Bleeding

Author

Jacqueline Bosch, PhD, Paul Moayyedi, MD, PhD, Marco Alings, MD, PhD, Alvaro Avezum, Jr., MD, PhD, Shrikant I. Bangdiwala, PhD, Alan Barkun, MD, CM, MSc, Federico Cassella, MD, Aloisio Marchi da Rocha, MD, PhD, Irfan Duzen, MD, Robert Enns, MD, Nauzer Forbes, MD, MSc, Leah Hamilton, MSc, Shofiqul Islam, PhD, Mustafa Kilickap, MD, MSc, Paul Kruger, MBBS, Yan Liang, MD, Jose C. Nicolau, MD, Rafael Nunes, MD, PhD, Martin O’Donnell, MD, PhD, Gustavo Oliveira, MD, PhD, Alejandro Rey, MD, Yihong Sun, MD, Thomas Vanassche, MD, Peter Verhamme, MD, Michael Walsh, MD, PhD, Zhenyu Wang, MD, Cynthia Wu, MD, Li Zhao, MD, Jun Zhu, MD, and John W. Eikelboom, MBBS

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: Bleeding is the most common adverse event in those with cardiovascular (CV) disease receiving antithrombotic therapy, and it most commonly occurs in the gastrointestinal (GI) tract. Clinicians often dismiss bleeding as an adverse event that is reversible with effective antithrombotic therapy, but bleeding is associated with substantial morbidity and mortality, most likely mediated through an increased risk of CV events. Reducing the burden of bleeding requires knowledge of the potentially modifiable risk factors for bleeding and the potentially modifiable risk factors for adverse outcomes after bleeding. Methods: INTERBLEED is an international, multicentre, 2-component, observational study, with an incident case-control study examining the risk factors for GI bleeding, and a prospective cohort study of risk factors for CV events after GI bleeding. Cases either have CV disease and present to the hospital with GI bleeding or develop GI bleeding during hospitalization. Controls have CV disease, but no history of GI bleeding. We use a questionnaire to obtain detailed information on known and potential risk factors for GI bleeding and for CV events and outcomes after bleeding. We obtain CV and anthropometric measurements, perform functional and cognitive assessments, and follow participants at 3 months and 12 months. Results: As of April 1, 2022, the study is ongoing in 10 countries at 31 centres and has recruited 2407 cases and 1478 controls. Conclusions: Knowledge of risk factors for bleeding, and risk factors for CV events and functional decline after bleeding, will help develop strategies to prevent bleeding and subsequent complications. Résumé: Contexte: L’hémorragie est l’effet indésirable le plus fréquent chez les patients atteints de maladies cardiovasculaires (CV) qui reçoivent un traitement antithrombotique, et elle survient le plus souvent dans le tractus gastro-intestinal (GI). Les cliniciens considèrent souvent l’hémorragie comme une simple manifestation indésirable réversible par un traitement antithrombotique efficace, mais une morbidité et une mortalité considérables y sont associées, probablement en raison d’un risque accru d’événements CV. Une réduction du fardeau de l’hémorragie nécessite une connaissance des facteurs de risque potentiellement modifiables tant de l’hémorragie que des événements indésirables qui surviennent après l’hémorragie. Méthodologie: INTERBLEED est une étude internationale, observationnelle et multicentrique à deux volets; le premier volet est une étude cas-témoins incidents visant à examiner les facteurs de risque d’hémorragie GI, alors que le second volet est une étude de cohorte prospective visant à examiner les facteurs de risque d’événements CV après une hémorragie GI. Les cas sont des patients atteints de maladies CV qui consultent les services hospitaliers pour une hémorragie GI ou qui présentent une hémorragie GI en cours d’hospitalisation. Les témoins sont des patients atteints de maladies CV, mais sans antécédents d’hémorragie GI. Un questionnaire est utilisé pour obtenir des renseignements détaillés au sujet de facteurs de risque connus et potentiels d’hémorragie GI et d’événements CV et d’autres résultats de santé après une hémorragie. Des mesures cardiovasculaires et anthropométriques ainsi que des évaluations fonctionnelles et cognitives sont réalisées, et les participants sont revus après trois mois et 12 mois. Résultats: En date du 1er avril 2022, l’étude est en cours dans 10 pays et 31 établissements de santé; 2 407 cas et 1 478 témoins ont été recrutés. Conclusions: La connaissance des facteurs de risque d’hémorragie, ainsi que des facteurs de risque d’événements CV et de déclin fonctionnel à la suite d’une hémorragie, aidera à mettre en place des stratégies pour prévenir les hémorragies et les complications qui peuvent en découler.

Published
2022
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2. Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Author

Gregory G. Schwartz, Michael Szarek, Vera A. Bittner, Rafael Diaz, Shaun G. Goodman, J. Wouter Jukema, Ulf Landmesser, Patricio López-Jaramillo, Garen Manvelian, Robert Pordy, Michel Scemama, Peter R. Sinnaeve, Harvey D. White, Ph Gabriel Steg, P.h. Gabriel Steg, Deepak L. Bhatt, Robert A. Harrington, Andreas M. Zeiher, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Corinne Hanotin, Guillaume Lecorps, Angèle Moryusef, William J. Sasiela, Jean-François Tamby, Philip E. Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N. Gotcheva, Juan-Carlos Prieto, Huo Yong, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S. Nieminen, Nicolas Danchin, Vakhtang Chumburidze, Nikolaus Marx, Evangelos Liberopoulos, Pablo Carlos Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M. Correa Flores, Rody G. Sy, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony J. Dalby, José Tuñón, H. Asita de Silva, Emil Hagström, Christian Müller, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean F.P. van Diepen, Matthew D. Wilson, Andrew Tze-Kay Yan, Lilia B. Schiavi, Marcelo Garrido, Andrés F. Alvarisqueta, Sonia A. Sassone, Anselmo P. Bordonava, Alberto E. Alves De Lima, Jorge M. Schmidberg, Ernesto A. Duronto, Orlando C. Caruso, Leonardo P. Novaretto, Miguel Angel Hominal, Oscar R. Montaña, Alberto Caccavo, Oscar A. Gomez Vilamajo, Alberto J. Lorenzatti, Luis R. Cartasegna, Gustavo A. Paterlini, Ignacio J. Mackinnon, Guillermo D. Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R. Codutti, Horacio O. Jure, Julio O.E. Bono, Adrian D. Hrabar, Julio A. Vallejos, Rodolfo A. Ahuad Guerrero, Federico Novoa, Cristian A. Patocchi, Cesar J. Zaidman, Maria E. Giuliano, Ricardo D. Dran, Marisa L. Vico, Gabriela S. Carnero, Pablo N. Guzman, Juan C. Medrano Allende, Daniela F. Garcia Brasca, Miguel H. Bustamante Labarta, Sebastian Nani, Eduardo D.S. Blumberg, Hugo R. Colombo, Alberto Liberman, Victorino Fuentealba, Hector L. Luciardi, Gabriel D. Waisman, Mario A. Berli, Ruben O. Garcia Duran, Horacio G. Cestari, Hugo A. Luquez, Jorge A. Giordano, Silvia S. Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon H. Waites, Nicholas Collins, Allan Soward, Chris L.S. Hii, James Shaw, Margaret A. Arstall, John Horowitz, Daniel Ninio, James F. Rogers, David Colquhoun, Romulo E. Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam J. Lehman, Constantine Aroney, Steven G.M. Coverdale, Paul J. Garrahy, Gregory Starmer, Mark Sader, Patrick A. Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Mathias C.M. Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Azra Durak-Nalbantic, Mehmed Kulić, Dusko Vulic, Adis Muslibegovic, Boris Goronja, Gilmar Reis, Luciano Sousa, Jose C. Nicolau, Flavio E. Giorgeto, Ricardo P. Silva, Lilia Nigro Maia, Rafael Rech, Paulo R.F. Rossi, Maria José A.G. Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M. Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler O.N. de Santos, Fernando Neuenschwander, Luiz C. Bodanese, Yorghos L. Michalaros, Freddy G. Eliaschewitz, Maria H. Vidotti, Paulo E. Leaes, Roberto V. Botelho, Sergio Kaiser, Euler Roberto F. Fernandes Manenti, Dalton B. Precoma, Jose C. Moura Jorge, Pedro Silva, Jose A. Silveira, Wladmir Saporito, Jose A. Marin Neto, Gilson S. Feitosa, Luiz Eduardo F. Ritt, Juliana A. de Souza, Fernando Costa, Weimar K.S.B. Souza, Helder J.L. Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V. Todorov, Fedya P. Nikolov, Elena S. Velcheva, Maria L. Tzekova, Haralambi O. Benov, Stanislav L. Petranov, Haralin S. Tumbev, Nina S. Shehova-Yankova, Dimitar T. Markov, Dimitar H. Raev, Mihail N. Mollov, Kostadin N. Kichukov, Katya A. Ilieva-Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M. Mincheva, Petar V. Lazov, Bojidar I. Dimov, Manohara Senaratne, James Stone, Jan Kornder, Stephen Pearce, Danielle Dion, Daniel Savard, Yves Pesant, Amritanshu Pandey, Simon Robinson, Gilbert Gosselin, Saul Vizel, Gordon Hoag, Ronald Bourgeois, Anne Morisset, Eric Sabbah, Bruce Sussex, Simon Kouz, Paul MacDonald, Ariel Diaz, Nicolas Michaud, David Fell, Raymond Leung, Tycho Vuurmans, Christopher Lai, Frank Nigro, Richard Davies, Gustavo Nogareda, Ram Vijayaraghavan, John Ducas, Serge Lepage, Shamir Mehta, James Cha, Robert Dupuis, Peter Fong, Sohrab Lutchmedial, Josep Rodes-Cabau, Hussein Fadlallah, David Cleveland, Thao Huynh, Iqbal Bata, Adnan Hameed, Cristian Pincetti, Sergio Potthoff, Juan C. Prieto, Monica Acevedo, Arnoldo Aguirre, Margarita Vejar, Mario Yañez, Guillermo Araneda, Mauricio Fernandez, Luis Perez, Paola Varleta, Fernando Florenzano, Laura Huidobro, Carlos A. Raffo, Claudia Olivares, Leonardo Nahuelpan, Humberto Montecinos, Jiyan Chen, Yugang Dong, Weijian Huang, Jianzhong Wang, Shi'An Huang, Zhuhua Yao, Xiang Li, Lan Cui, Wenhua Lin, Yuemin Sun, Jingfeng Wang, Jianping Li, Xuelian Zhang, Hong Zhu, Dandan Chen, Lan Huang, Shaohong Dong, Guohai Su, Biao Xu, Xi Su, Xiaoshu Cheng, Jinxiu Lin, Wenxia Zong, Huanming Li, Yi Feng, Dingli Xu, Xinchun Yang, Yuannan Ke, Xuefeng Lin, Zheng Zhang, Zeqi Zheng, Zhurong Luo, Yundai Chen, Chunhua Ding, Yi Zhong, Yang Zheng, Xiaodong Li, Daoquan Peng, Shuiping Zhao, Ying Li, Xuebo Liu, Meng Wei, Shaowen Liu, Yihua Yu, Baiming Qu, Weihong Jiang, Yujie Zhou, Xingsheng Zhao, Zuyi Yuan, Ying Guo, Xiping Xu, Xubo Shi, Junbo Ge, Guosheng Fu, Feng Bai, Weiyi Fang, Xiling Shou, Xiangjun Yang, Jian'An Wang, Meixiang Xiang, Yingxian Sun, Qinghua Lu, Ruiyan Zhang, Jianhua Zhu, Yizhou Xu, Zhongcai Fan, Tianchang Li, Chun Wu, Nicolas Jaramillo, Gregorio Sanchez Vallejo, Diana C. Luna Botia, Rodrigo Botero Lopez, Dora I. Molina De Salazar, Alberto J. Cadena Bonfanti, Carlos Cotes Aroca, Juan Diego Higuera, Marco Blanquicett, Sandra I. Barrera Silva, Henry J. Garcia Lozada, Julian A. Coronel Arroyo, Jose L. Accini Mendoza, Ricardo L. Fernandez Ruiz, Alvaro M. Quintero Ossa, Fernando G. Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A. Urina Triana, Angela M. Fernandez Trujillo, Maja Strozzi, Siniša Car, Melita Jerić, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, Josef Stasek, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Premysl Svab, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H. Poulsen, Bent Raungaard, Peter Clemmensen, Lia E. Bang, Ole May, Morten Bøttcher, Jens D. Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S. Kristensen, Piotr Maria Walichiewicz, Jens D. Lomholdt, Ib C. Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Heikki Huikuri, Juhani Airaksinen Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Florence Leclercq, Abdelkader Belhassane, Nicolas Delarche, Franck Boccara, Franck Paganelli, Jérôme Clerc, Francois Schiele, Victor Aboyans, Vincent Probst, Jacques Berland, Thierry Lefèvre, Bernard Citron, Irakli Khintibidze, Tamaz Shaburishvili, Zurab Pagava, Ramaz Ghlonti, Zaza Lominadze, George Khabeishvili, Rayyan Hemetsberger, Kemala Edward, Ursula Rauch-Kröhnert, Matthias Stratmann, Karl-Friedrich Appel, Ekkehard Schmidt, Heyder Omran, Christoph Stellbrink, Thomas Dorsel, Emmanouil Lianopoulos, Hans Friedrich Vöhringer, Roger Marx, Andreas Zirlik, Detlev Schellenberg, Thomas Heitzer, Ulrich Laufs, Christian Werner, Stephan Gielen, Sebastian Nuding, Bernhard Winkelmann, Steffen Behrens, Karsten Sydow, Mahir Karakas, Gregor Simonis, Thomas Muenzel, Nikos Werner, Stefan Leggewie, Dirk Böcker, Rüdiger Braun-Dullaeus, Nicole Toursarkissian, Michael Jeserich, Matthias Weißbrodt, Tim Schaeufele, Joachim Weil, Heinz Völler, Johannes Waltenberger, Mohammed Natour, Susanne Schmitt, Dirk Müller-Wieland, Stephan Steiner, Lothar Heidenreich, Elmar Offers, Uwe Gremmler, Holger Killat, Werner Rieker, Sotiris Patsilinakos, Athanasios Kartalis, Athanassios Manolis, Dimitrios Sionis, Geargios Chachalis, Ioannis Skoumas, Vasilios Athyros, Panagiotis Vardas, Frangkiskos Parthenakis, John Lekakis, Apostolos Hatzitolios, Sergio R. Fausto Ovando, Juan L. Arango Benecke, Edgar R. Rodriguez De Leon, Bryan P.Y. Yan, David C.W. Siu, Tibor Turi, Bela Merkely, Imre Ungi, Geza Lupkovics, Lajos Nagy, András Katona, István Édes, Gábor Müller, Iván Horvath, Tibor Kapin, Zsolt Szigeti, József Faluközy, Mukund Kumbla, Manjinder Sandhu, Sharath Annam, Naveen Reddy Proddutur, Reddy Regella, Rajendra K. Premchand, Ajaykumar Mahajan, Sudhir Pawar, Atul D. Abhyanakar, Prafulla Kerkar, Ravishankar A. Govinda, Abraham Oomman, Dhurjati Sinha, Sachin N. Patil, Dhiman Kahali, Jitendra Sawhney, Abhijeet B. Joshi, Sanjeev Chaudhary, Pankaj Harkut, Santanu Guha, Sanjay Porwal, Srimannarayana Jujjuru, Ramesh B. Pothineni, Minguel R. Monteiro, Aziz Khan, Shamanna S. Iyengar, Jasprakash Singh Grewal, Manoj Chopda, Mahesh C. Fulwani, Aparna Patange, Patil Sachin, Vijay K. Chopra, Naresh K. Goyal, Rituparna Shinde, Gajendra V. Manakshe, Nitin Patki, Sumeet Sethi, Vengatesh Munusamy, Sunil Karnaand Sunil Thanvi, Srilakshmi Adhyapak, Chandrakant Patil, Ulhas Pandurangi, Rishabh Mathur, Jugal Gupta, Suhas Kalashetti, Ajit Bhagwat, Bagirath Raghuraman, Shiv Kumar Yerra, Prasant Bhansali, Rohidas Borse, Patil Rahul, Srihari Das, Vinay Kumar, Jabir Abdullakutty, Shireesh Saathe, Priya Palimkar, Jabir Abdullkutty, Shireesh Sathe, Shaul Atar, Michael Shechter, Morris Mosseri, Yaron Arbel, Chorin Ehud, Havakuk Ofer, Chaim Lotan, Uri Rosenschein, Amos Katz, Yaakov Henkin, Adi Francis, Marc Klutstein, Eugenia Nikolsky, Robert Zukermann, Yoav Turgeman, Majdi Halabi, Alon Marmor, Ran Kornowski, Michael Jonas, Offer Amir, Yonathan Hasin, Yoseph Rozenman, Shmuel Fuchs, Vered Zvi, Osamah Hussein, Dov Gavish, Zvi Vered, Yoseph Caraco, Mazen Elias, Naveh Tov, Efrat Wolfovitz, Michael Lishner, Nizar Elias, Giancarlo Piovaccari, Annamaria De Pellegrin, Raffaella Garbelotto, Gabriele Guardigli, Valgimigli Marco, Giovanni Licciardello, Carla Auguadro, Filippo Scalise, Claudio Cuccia, Alessandro Salvioni, Giuseppe Musumeci, Michelle Senni, Paolo Calabrò, Salvatore Novo, Pompilio Faggiano, Marco Metra, Nicoletta B. De Cesare, Sergio Berti, Claudio Cavallini, Enrico Puccioni, Marcello Galvani, Maurizio Tespili, Piermarco Piatti, Michela Palvarini, Giuseppe De Luca, Roberto Violini, Alessandro De Leo, Zoran Olivari, Pasquale Perrone Filardi, Maurizio Ferratini, Vittorio Racca, Kazuoki Dai, Yuji Shimatani, Haruo Kamiya, Kenji Ando, Yoshihiro Takeda, Yoshihiro Morino, Yoshiki Hata, Kazuo Kimura, Koichi Kishi, Ichiro Michishita, Hiroki Uehara, Toshinori Higashikata, Atsushi Hirayama, Keiji Hirooka, Yasuji Doi, Satoru Sakagami, Shuichi Taguchi, Akihiro Koike, Hiroyuki Fujinaga, Shinji Koba, Ken Kozuma, Tomohiro Kawasaki, Yujiro Ono, Masatoshi Shimizu, Yousuke Katsuda, Atsuyuki Wada, Toshiro Shinke, Junya Ako, Kenshi Fujii, Toshiyuki Takahashi, Tomohiro Sakamoto, Koichi Nakao, Yutaka Furukawa, Hiroshi Sugino, Ritsu Tamura, Toshiaki Mano, Masaaki Uematsu, Noriaki Utsu, Kashima Ito, Takuya Haraguchi, Katsuhiko Sato, Yasunori Ueda, Akira Nishibe, Kazuteru Fujimoto, Motomaru Masutani, Jung Han Yoon, Hack-Lyoung Kim, Hun Sik Park, In-Ho Chae, Moo Hyun Kim, Myung Ho Jeong, Seungwoon Rha, Chongjin Kim, Hae Young Kim, Taekjong Hong, Seung-Jea Tahk, Youngkwon Kim, Arija Busmane, Natalija Pontaga, Aldis Strelnieks, Iveta Mintale, Iveta Sime, Zaneta Petrulioniene, Roma Kavaliauskiene, Ruta Jurgaitiene, Gintare Sakalyte, Rimvydas Slapikas, Sigute Norkiene, Nerijus Misonis, Aleksandras Kibarskis, Raimondas Kubilius, Stojko Bojovski, Nensi Lozance, Aleksandar Kjovkaroski, Snezana Doncovska, Tiong Kiam Ong, Sazzli Kasim, Oteh Maskon, Balachandran Kandasamy, Houng B. Liew, Wan Mohd Izani Wan Mohamed, Armando García Castillo, Jorge Carrillo Calvillo, Pedro Fajardo Campos, Juan Carlos Núñez Fragoso, Edmundo Alfredo Bayram Llamas, Marco Antonio Alcocer Gamba, Jaime Carranza Madrigal, Luis Gerardo González Salas, Enrique López Rosas, Belinda González Díaz, Eduardo Salcido Vázquez, Alfredo Nacoud Ackar, Guillermo Antonio Llamas Esperón, Carlos Rodolfo Martínez Sánchez, María Guerrero De Leon, Rodrigo Suarez Otero, Guillermo Fanghänel Salmón, Jesús Antonio Pérez Ríos, José Angel Garza Ruíz, Robert W. Breedveld, Margriet Feenema-Aardema, Alida Borger-Van Der Burg, Pieter A.M. Hoogslag, Harry Suryapranata, Antonius Oomen, Paulus Van Haelst, Margriet Feenema-Aradema, Jacobijne J. Wiersma, Dirk Basart, Ruud M.A. Van Der Wal, Peter Zwart, Pascalle Monraats, Henricus Van Kesteren, Ioannis Karalis, Johan Jukema, Gerardus J.E. Verdel, Bart R.G. Brueren, Roland PTh Troquay, Eric P. Viergever, Nadea Y.Y. Al-Windy, Gerard L. Bartels, Jan H. Cornel, Walter R.M. Hermans, Johannes P.R. Herrman, Robert J. Bos, Reginald G.E.J. Groutars, Coenraad C. Van Der Zwaan, Refik Kaplan, Raymond Lionarons, Eelko Ronner, Bjorn E. Groenemeijer, Patrick N.A. Bronzwaer, Anho A.H. Liem, Bernard J.W.M. Rensing, Marcel J.J.A. Bokern, Remco Nijmeijer, Ferry M.R.J. Hersbach, Frank F. Willems, Antonius T.M. Gosselink, Saman Rasoul, John Elliott, Gerard Wilkins, Raewyn Fisher, Douglas Scott, Hamish Hart, Ralph Stewart, Scott Harding, Ian Ternouth, Nicholas Fisher, Samuel Wilson, Denise Aitken, Russell Anscombe, Laura Davidson, Tadeusz Tomala, Ottar Nygård, Jon Arne Sparby, Kjell Andersen, Lars Gullestad, Jarle Jortveit, Peter S. Munk, Erlend gyllensten Singsaas, Ulf Hurtig, Jorge R. Calderon Ticona, Julio R. Durand Velasquez, Sandra A. Negron Miguel, Enrique S. Sanabria Perez, Jesus M. Carrion Chambilla, Carlos A. Chavez Ayala, Reynaldo P. Castillo Leon, Rolando J. Vargas Gonzales, Jose D. Hernandez Zuniga, Luis A. Camacho Cosavalente, Jorge E. Bravo Mannucci, Javier Heredia Landeo, Nassip C. Llerena Navarro, Yudy M. Roldan Concha, Víctor E. Rodriguez Chavez, Henry A. Anchante Hernandez, Carlos A. Zea Nunez, Walter Mogrovejo Ramos, Arthur Ferrolino, Rosa Allyn G. Sy, Louie Tirador, Generoso Matiga, Raul Martin Coching, Alisa Bernan, Gregorio Rogelio, Dante D. Morales, Edgar Tan, Dennis Jose Sulit, Adrian Wlodarczak, Krystyna Jaworska, Grzegorz Skonieczny, Lidia Pawlowicz, Pawel Wojewoda, Benita Busz-Papiez, Janusz Bednarski, Aleksander Goch, Pawel Staneta, Elzbieta Dulak, Krzysztof Saminski, Wlodzimierz Krasowski, Wanda Sudnik, Aleksander Zurakowski, Marcin Skorski, Roman Lysek, Beata Miklaszewicz, Jacek Kubica, Jan Andrzej Lipko, Edyta Kostarska-Srokosz, Marek Piepiorka, Anna Drzewiecka, Ryszard Sciborski, Arkadiusz Stasiewski, Tomasz Blicharski, Leszek Bystryk, Michal Szpajer, Marek Korol, Tomasz Czerski, Ewa Mirek-Bryniarska, Jacek Gniot, Andrzej Lubinski, Jerzy Gorny, Edward Franek, Grzegorz Raczak, Hanna Szwed, Pedro Monteiro, Jose Mesquita Bastos, Helder H. Pereira, Dinis Martins, Filipe Seixo, Carlos Mendonça, Ana Botelho, Francisca Caetano, Bogdan Minescu, Octavian Istratoaie, Dan N. Tesloianu, Gabriel Cristian, Silviu Dumitrescu, Cristian G.C. Podoleanu, Mircea C.A. Constantinescu, Cristina M. Bengus, Constantin Militaru, Doina Rosu, Irinel R. Parepa, Adrian V. Matei, Tom M. Alexandru, Mihaela Malis, Ioan Coman, Rodica Stanescu-Cioranu, Doina Dimulescu, Yury Shvarts, Olga Orlikova, Zhanna Kobalava, Olga L. Barbarash, Valentin Markov, Nadezhda Lyamina, Alexander Gordienko, Konstantin Zrazhevsky, Alexander Y. Vishnevsky, Victor Gurevich, Raisa Stryuk, Nikita V. Lomakin, Igor Bokarev, Tatiana Khlevchuk, Sergey Shalaev, Larisa Khaisheva, Petr Chizhov, Inna Viktorova, Natalya Osokina, Vladimir Shchekotov, Evgenia Akatova, Galina Chumakova, Igor Libov, Mikhail I. Voevoda, Tatyana V. Tretyakova, Evgeny Baranov, Sergey Shustov, Sergey Yakushin, Ivan Gordeev, Niiaz Khasanov, Olga Reshetko, Tatiana Sotnikova, Olga Molchanova, Konstantin Nikolaev, Liudmila Gapon, Elena Baranova, Zaur Shogenov, Elena Kosmachova, Yuriy Karpov, Anton Povzun, Liudmila Egorova, Vadim V. Tyrenko, Igor G. Ivanov, Masterov Ilya, Sergey Kanorsky, Dragan Simic, Nikola Ivanovic, Goran Davidovic, Nebojsa Tasic, Milika R. Asanin, Stevo Stojic, Svetlana R. Apostolovic, Stevan Ilic, Biljana Putnikovic Tosic, Aleksandar Stankovic, Aleksandra Arandjelovic, Slavica Radovanovic, Branislava Todic, Jovan Balinovac, Dragan V. Dincic, Petar Seferovic, Ana Karadzic, Slobodan Dodic, Sinisa Dimkovic, Tamara Jakimov, Kian-Keong Poh, Hean Yee Ong, Justin Tang I-Shing, Karol Micko, Jan Nociar, Daniel Pella, Peter Fulop, Marian Hranai, Juraj Palka, Juraj Mazur, Ivan Majercák, Andrej Dzupina, František Fazekas, Jozef Gonsorcik, Viliam Bugan, Juraj Selecky, Gabriel Kamensky, Jaroslava Strbova, Rudolf Smik, Andrej Dukat, Peter Olexa, Ivan Žuran, Janez Poklukar, Nataša Černič Šuligoj, Matija Cevc, Henry P. Cyster, Naresh Ranjith, Clive Corbett, Junaid Bayat, Ellen Makoali Makotoko, Hendrik du Toit Theron, Ilse E. Kapp, Matthys M. de V Basson, Hanlie Lottering, Dina Van Aswegen, Louis J. Van Zyl, Peter J. Sebastian, Thayabran Pillay, Jan A. Saaiman, Patrick J. Commerford, Soraya Cassimjee, Garda Riaz, Iftikhar O. Ebrahim, Mahomed Sarvan, Joseph H. Mynhardt, Helmuth Reuter, Rajendran Moodley, Manuel Vida, Angel R. Cequier Fillat, Vicente Bodí Peris, Francisco Fuentes Jimenez, Francisco Marín, Jose M. Cruz Fernández, Rafael Jesus Hidalgo Urbano, Blas Gil-Extremera, Pablo Toledo, Fernando Worner Diz, David Garcia-Dorado, Andres Iñiguez, José Tuñón Fernández, Jose R. Gonzalez-Juanatey, Javier Fernandez Portales, Fernando Civeira Murillo, Laia Matas Pericas, Jose Luis Zamorano, Manuel De Mora Martin, Jordi Bruguera Cortada, Joaquin J. Alonso Martin, Jose Maria Serrano Antolin, José R. De Berrazueta Fernández, José Antonio Vázquez de Prada, Jose Francisco Díaz Fernández, José Alberto García Lledó, Juan Cosín Sales, Javier Botas Rodriguez, Gabriel Gusi Tragant, Amparo Benedicto, Carlos Gonzalez-Juanatey, Mercedes Camprubí Potau, Ignacio Plaza Perez, César Morís De La Tassa, Pablo Loma-Osorio Rincon, Javier Balaguer Recena, Juan M. Escudier, Antonio Coca Payeras, Norberto Alonso Orcajo, Pedro Valdivielso, Godwin Constantine, Ruvaiz Haniffa, Nirmali Tissera, Stanley Amarasekera, Chandrike Ponnamperuma, Nimali Fernando, Kaputella Fernando, Jayanthimala Jayawardena, Santharaj Wijeyasingam, Gotabhaya Ranasinghe, Ruvan Ekanayaka, Sepalika Mendis, Vajira Senaratne, Gnanamoorthy Mayurathan, Ajantha Rajapaksha, Thilak Sirisena, Jagath I. Herath, Naomali Amarasena, Stefan Berglund, Gundars Rasmanis, Ola Vedin, Nils Witt, Georgios Mourtzinis, Peter Nicol, Ole Hansen, Stefano Romeo, Steen Agergaard Jensen, Ingemar Torstensson, Ulf Ahremark, Torbjörn Sundelin, Tiziano Moccetti, Francois Mach, Ronald Binde, Oliver Gämperli, Wei-Chuan Tsai, Kwo-Chang Ueng, Wen-Ter Lai, Ming-En Liu, Juey-Jen Hwang, Wei-Hsian Yin, I-Chang Hsieh, Ming-Jer Hsieh, Wei Hsiang Lin, Jen-Yuan Kuo, Tsuei-Yuan Huang, Chih-Yuan Fang, Pinij Kaewsuwanna, Wasant Soonfuang, Woravut Jintapakorn, Apichard Sukonthasarn, Nattawut Wongpraparut, Krisada Sastravaha, Nakarin Sansanayudh, Wirash Kehasukcharoen, Dilok Piyayotai, Paiboon Chotnoparatpat, Ahmet Camsari, Hakan Kultursay, Bulent Mutlu, Murat Ersanli, Mustafa Demirtas, Cevat Kirma, Ertan Ural, Lale Koldas, Oleksandr Karpenko, Alexander Prokhorov, Ihor Vakaluyk, Halyna Myshanych, Dmytro Reshotko, Valeriy Batushkin, Leonid Rudenko, Ihor Kovalskyi, Mykola Kushnir, Vira Tseluyko, Yuriy Mostovoy, Mykola Stanislavchuk, Yulian Kyiak, Yuriy Karpenko, Yaroslav Malynovsky, Andriy Klantsa, Oles Kutniy, Ekaterina Amosova, Viktor Tashchuk, Oleh Leshchuk, Mykola Rishko, Mykola Kopytsya, Andriy Yagensky, Mykola Vatutin, Andriy Bagriy, Olga M. Barna, Olexiy Ushakov, Georgiy Dzyak, Borys Goloborodko, Anatolii Rudenko, Volodymyr Zheleznyy, Jasper Trevelyan, Azfar Zaman, Kaeng Lee, Andrew Moriarty, Rajesh K. Aggarwal, Piers Clifford, Yuk-Ki Wong, Syed M.R. Iqbal, Eduardas Subkovas, Denise Braganza, David Sarkar, Robert Storey, Huw Griffiths, Sam Mcclure, Rangasamy Muthusamy, Simon Smith, John Kurian, Terry Levy, Craig Barr, Honer Kadr, Robert Gerber, Audrius Simaitis, Handrean Soran, Anthony Mathur, Adrian Brodison, Mohammad Ayaz, Muhammad Cheema, Richard Oliver, Simon Thackray, Telal Mudawi, Gohar Rahman, Ayyaz Sultan, Timothy Reynolds, David Sharman, null david Sprigings, Rob Butler, Peter Wilkinson, Gregory Y.H. Lip, Julian Halcox, Sean Gallagher, Nicholas Ossei-Gerning, Gil Vardi, Duccio Baldari, David Brabham, Charles Treasure, Charles Dahl, Bruce Palmer, Alan Wiseman, Abul Khan, Sanjeev Puri, Ann Elizabeth Mohart, Carlos Ince, Enrique Flores, Scott Wright, Shi-Chi Cheng, Michael Rosenberg, William Rogers, Edward Kosinski, Les Forgosh, Jonathan Waltman, Misal Khan, Mohammad Shoukfeh, Georges Dagher, Patrick Cambier, Ira Lieber, Priya Kumar, Cara East, Perry Krichmar, Mian Hasan, Lindsey White, Thomas Knickelbine, Thomas Haldis, Eve Gillespie, Thomas Amidon, David Suh, Imran Arif, Mouhamad Abdallah, Faiq Akhter, Eric Carlson, Michael D'Urso, Fadi El-Ahdab, William Nelson, Katie Moriarty, Barry Harris, Steven Cohen, Luther Carter, Daniel Doty, Kenneth Sabatino, Tariq Haddad, Amir Malik, Sunder Rao, Angel Mulkay, Ion Jovin, Kim Klancke, Vinay Malhotra, Sai K. Devarapalli, Michael Koren, Harish Chandna, George Dodds, Tauqir Goraya, James Bengston, Matthew Janik, Joseph Moran, Andrew Sumner, John Kobayashi, William Davis, Shahram Yazdani, John Pasquini, Maitreya Thakkar, Amarnath Vedere, Wayne Leimbach, James Rider, Sarah fenton, Narendra Singh, Anil V. Shah, Denise Janosik, Carl Pepine, Brett Berman, Joseph Gelormini, Christopher Daniels, Kerensky Richard, Friederike Keating, Nicholas I. Kondo, Sanjay Shetty, Howard Levite, Winfried Waider, Theodore Takata, Mazen Abu-Fadel, Vipul Shah, Rahul Aggarwal, Mark Izzo, Anil Kumar, Brack Hattler, Rose Do, Chad Link, Anna Bortnick, George Kinzfogl, Arnold Ghitis, John Larry, Edward Teufel, Peter Kuhlman, Brent Mclaurin, Wenwu Zhang, Stephen Thew, Jalal Abbas, Matthew White, Othman Islam, Sumeet Subherwal, Nandkishore Ranadive, Babak Vakili, Christian Gring, David Henderson, Timothy Schuchard, Naim Farhat, Geoffrey Kline, Sharan Mahal, Jack Whitaker, Shawn Speirs, Rolf Andersen, Nizar Daboul, Phillip Horwitz, Firas Zahr, George Ponce, Zubair Jafar, Joseph Mcgarvey, Vipul Panchal, Stephen Voyce, Thomas Blok, William Sheldon, Masoud M. Azizad, Carsten Schmalfuss, Mark Picone, Robert Pederson, William Herzog, Keith Friedman, Jason Lindsey, Rosemary Nowins, Eichenlaub Timothy, Parilak Leonard, Norman Lepor, Mahfouz El Shahawy, Howard Weintraub, Anand Irimpen, Alvaro Alonso, Wade May, Daniels Christopher, Thomas Galski, Alan Chu, Freny Mody, Ebrahimi Ramin, Zachary Hodes, Joseph Rossi, Gregory Rose, James Fairlamb, Charles Lambert, Ajit Raisinghani, Antonio Abbate, George Vetrovec, Marilyn King, Charles Carey, Jaime Gerber, Liwa Younis, Hyeun Park, Mladen Vidovich, Thomas Knutson, Dennis Friedman, Fred Chaleff, Arthur Loussararian, Phillip Rozeman, Carey Kimmelstiel, Jeffrey Kuvin, Kevin Silver, Malcolm Foster, Glen Tonnessen, Andrey Espinoza, Mohamadali Amlani, Andreas Wali, Christopher Malozzi, Geert T. Jong, Clara Massey, Keattiyoat Wattanakit, Philip J. O'Donnell, Dinesh Singal, Naseem Jaffrani, Sridhar Banuru, Daniel Fisher, Mark Xenakis, Neal Perlmutter, Ravi Bhagwat, James Strader, Ronald Blonder, Ayim Akyea-Djamson, Ajay Labroo, Kwan Lee, H. John Marais, Edmund Claxton, Robert Weiss, Rohr Kathryn, Martin Berk, Peter Rossi, Parag Joshi, Amit Khera, Ajit S. Khaira, Greg Kumkumian, Steven Lupovitch, Joshua Purow, Stephen Welka, David Hoffman, Stuart Fischer, Eugene Soroka, Donald Eagerton, Samir Pancholy, Michael Ray, Norman Erenrich, Michael Farrar, Stewart Pollock, William J. French, Steve Diamantis, Douglas Guy, Lawrence Gimple, Mark Neustel, Steven Schwartz, Edward Pereira, Seals Albert, Douglas Spriggs, Janet Strain, Suneet Mittal, Anthony Vo, Majed Chane, Jason Hall, Nampalli Vijay, Kapildeo Lotun, F. Martin Lester, Ahed Nahhas, Theodore Pope, Paul Nager, Rakesh Vohra, Mukesh Sharma, Riyaz Bashir, Hinan Ahmed, Michael Berlowitz, Robert Fishberg, Robert Barrucco, Eric Yang, Michael Radin, Daniel Sporn, Dwight Stapleton, Steven Eisenberg, Joel Landzberg, Martin Mcgough, Samir Turk, Michael Schwartz, P. Sandy Sundram, Diwakar Jain, Mark Zainea, Carlos Bayron, Ronald Karlsberg, Suhail Dohad, Henry Lui, William Keen, Donald Westerhausen, Sandeep Khurana, Himanshu Agarwal, Jessica Birchem, William Penny, Mark Chang, Sherrill Murphy, John Henry, Branislav Schifferdecker, John M Gilbert, Gopal Chalavarya, Charles Eaton, John F. Schmedtje, Stuart Christenson, Imran Dotani, Douglas Denham, Alexander Macdonell, Paul Gibson, Aref Rahman, Tammam Al Joundi, Nizar Assi, Gary Conrad, Purushotham Kotha, Michael Love, Gregory Giesler, Howard Rubenstein, Dawood Gamil, Laura Akright, Justine Krawczyk, Joanne Cobler, Terry Wells, James Welker, Robert Foster, Richard Gilmore, Jay Anderson, Douglas Jacoby, Bill Harris, Geraldine Gardner, Ramprasad Dandillaya, Kishor Vora, John Kostis, John Hunter, David Laxson, Eric Ball, Flavia Egydio, Anelise Kawakami, Janaina Oliveira, Julianna Wozniak, Alexander Matthews, Caroline Ratky, Janine Valiris, Lisa Berdan, Anita Hepditch, Kirby Quintero, Tyrus Rorick, Melissa Westbrook, Andrea Pascual, Carla Rovito, Madeleine Bezault, Elodie Drouet, Tabassome Simon, Caroline Alsweiler, Anne Luyten, Julie Butters, Liddy Griffith, Michelle Shaw, Lena Grunberg, Shahidul Islam, Marie-France Brégeault, Nathalie Bougon, Douglas Faustino, Sylvie Fontecave, Judith Murphy, Melanie Verrier, null Veronique Agnetti, Dorthe Andersen, Emmy Badreddine, Mhamed Bekkouche, Cecile Bouancheau, Imane Brigui, Maddy Brocklehurst, Joseph Cianciarulo, Dawn Devaul, Szilvia Domokos, Cecile Gache, Caroline Gobillot, Severine Guillou, Jan Healy, Megan Heath, Gayatri Jaiwal, Carine Javierre, Julien Labeirie, Myriam Monier, Ulises Morales, Asmaa Mrabti, Bicky Mthombeni, Betim Okan, Lucile Smith, Jennifer Sheller, Sebastien Sopena, Valerie Pellan, Fadela Benbernou, Nafissa Bengrait, Maud Lamoureux, Katarina Kralova, Raphael Bejuit, Anthony Coulange, Christelle Berthou, Jérôme Repincay, Christelle Lorenzato, Alexis Etienne, Valerie Gouet, Virginie Loizeau, Mickael Normand, Anne Ourliac, Christelle Rondel, Antony Adamo, Pascale Beltran, Pauline Barraud, Helene Dubois-Gache, Benjamin Halle, Lamia Metwally, Maxime Mourgues, Marc Sotty, Marion Vincendet, Raluca Cotruta, Zhu Chengyue, Dominique Fournie-Lloret, Christine Morrello, Aurelie Perthuis, Patrick Picault, Isabelle Zobouyan, Helen M. Colhoun, Michael A. Dempsey, Mark A. McClanahan, Masira, and Laucevičius, Aleksandras

Subjects
Male, Acute coronary syndrome, medicine.medical_specialty, Cardiac & Cardiovascular Systems, Randomization, PCSK9 inhibitor, LOW-DENSITY-LIPOPROTEIN, Antibodies, Monoclonal, Humanized, acute coronary syndrom, Placebo, Gastroenterology, lipoprotein(a), Internal medicine, medicine, Humans, Low-density lipoprotein cholesterol, Aged, Alirocumab, RISK, low-density lipoprotein cholesterol, Science & Technology, biology, business.industry, PCSK9, PCSK9 Inhibitors, Hazard ratio, ALIROCUMAB, acute coronary syndrome, Cholesterol, LDL, Lipoprotein(a), Middle Aged, EFFICACY, medicine.disease, Cardiovascular Diseases, CARDIOVASCULAR-DISEASE, SAFETY, Cardiovascular System & Cardiology, biology.protein, Female, lipids (amino acids, peptides, and proteins), STATIN, low-density lipoprotein, cholesterol PCSK9 inhibitor, CORONARY, Cardiology and Cardiovascular Medicine, business, Life Sciences & Biomedicine, Mace
Abstract

Digital, Background Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402), Ciencias Médicas y de la Salud

Published
2021
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3. List of Contributors

Author

Toshio Asakura, G Avenard, P Boivin, M A Borchardt, George H Brewer, B Chaillot, O Charansonney, M Chassaigne, C Crone, E Dellacherie, Robert D Dick, M Duruble, M A Duvelleroy, Y Gauduel, Michael P Hlastala, Ernesto E Di Iorio, R Itti, P Labrude, J L Martin, A Mayevsky, C Nicolau, L Philippe, George K Radda, Michael P Reilly, C Ropars, J F Stolz, O Stucker, B Tannenbaum, B Teisseire, R Trouve, C R Valeri, E Vicaut, C Vieilledent, C Vigneron, Kaspar H Winterhalter, R D Woodson, E Yoles, and N Zarchin

Published
1986
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4. Significance of Low Hemoglobin Oxygen Affinity

Author

C. Vieilledent, B. Teisseire, C. Nicolau, and Claude Ropars

Subjects
P50, Biochemistry, In vivo, Chemistry, Biophysics, chemistry.chemical_element, Oxygen–haemoglobin dissociation curve, Blood flow, Oxygenation, Hemoglobin, Oxygen affinity, Oxygen
Abstract

Publisher Summary This chapter discusses the significance of low hemoglobin oxygen affinity. The chapter examines the following points: (1) oxygen hemoglobin dissociation curve (ODC), rightward shifts in physiopathology; (2) the response of mathematical models to right ODC shifts; (3) how to obtain in vivo high P50 values; (4) physiological consequences of right ODC shifts in normal animals; and (5) the consequences of high P50 values in pathological models. Lowering the hemoglobin affinity for oxygen is physiologically important whenever a limitation of blood flow or reduction in hemoglobin concentration impair systemic oxygenation. One may conjecture that with conditions of tissue hypoxia, an in vivo decrease in O2 affinity has potential physiological advantages Moreover, in the case of blood flow reduction, high P50 values induce higher tissue oxygenation by increasing oxygen release.

Published
1986
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6. Incorporation of Allosteric Effectors of Hemoglobin in Red Blood Cells. Biochemical and Physiological Effects

Author

C. Nicolau, Claude Ropars, and B. Teisseire

Subjects
P50, chemistry, Biochemistry, Allosteric regulation, Biophysics, chemistry.chemical_element, Bohr effect, Hemoglobin, Partial pressure, Biology, Oxygen, Intracellular, Microcirculation
Abstract

Publisher Summary This chapter reviews the biochemical and physiological effects of the incorporation of allosteric effectors of hemoglobin in red blood cells. The amount of O2 that can be released in a particular organ depends on the critical O2 partial pressure characteristic for the organ and on the architecture of the microvasculature. This O2 release capacity is controlled by the microcirculation and molecular parameters of the intracellular Hb. The O2 release capacity can be enhanced by an increase in the co-operability of the Hb molecule; and/or by right shifting of the entire O2-binding curve toward higher O2 partial pressures. An abnormally high affinity of hemoglobin for oxygen shifts the O2-binding curve to the left and the P50 (O2 partial pressure at which 50% saturation of hemoglobin occurs) decreases causing a lower oxygen release to the tissues. In human RBC, the right-shift is controlled by several allosteric mechanisms, such as Bohr effect, 2, 3-bis-phosphoglycerate (DPG), and CO2-binding.

Published
1986
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7. Layer upon layer: Imaging techniques of bladder matrix stone: A case report.

Author

Paredes C, Paño B, Sebastià C, Padulles B, Rodríguez L, Borrell-Vega J, and Nicolau C

Abstract

Matrix lithiasis within the bladder is an extremely rare and diagnostically challenging condition, characterized by its atypical presentation and complex imaging appearance. We report the case of a 69-year-old woman with nonspecific urinary symptoms, including hematuria and abdominal pain. Initial ultrasonography revealed an echogenic lesion on the bladder wall, leading to further investigations using computed tomography (CT) and magnetic resonance imaging (MRI). CT imaging initially delineated the lesion's structure, revealing a complex, multilayered cystic mass. Subsequent MRI provided detailed insights into the internal architecture of the mass, further elucidating its layered structure. Although a parasitic etiology was initially suspected, matrix lithiasis was later confirmed. This case highlights the critical role of a comprehensive imaging strategy in diagnosing rare urological conditions and emphasizes the importance of multimodal imaging in differentiating potential diagnoses., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Published
2024
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8. Primarian fallopian tube carcinoma: Clinical and radiological keys for diagnosis.

Author

Zhan D, Saavedra H, Torne A, Saco A, Cabedo L, Nicolau C, and Sebastia C

Abstract

Primary fallopian tube carcinoma (PFTC) is seldom diagnosed preoperatively and is often mistaken for epithelial ovarian carcinoma (EOC). This report details a case of primary high-grade serous carcinoma (HGSC) of the fallopian tube, highlighting radiological and clinical indicators to aid in accurate diagnosis and avoid misdiagnosis. A 46-year-old premenopausal woman presented with symptoms and a transvaginal ultrasound (TVUS) indicating a malignant ovarian tumor. Further imaging with CT and MRI revealed a solid-cystic mass suggestive of a fallopian tube tumor rather than an ovarian origin. Oncological surgery confirmed the presence of a high-grade serous carcinoma in the fallopian tube. This case underscores the diagnostic challenges of PFTC and the superior sensitivity and specificity of MRI over CT and US in distinguishing adnexal lesions. Key MRI features such as the sausage-shaped mass and associated hematosalpinx were crucial in differentiating PFTC from EOC. The report emphasizes the importance of considering PFTC in differential diagnoses of adnexal masses to ensure accurate preoperative identification., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Published
2024
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9. The role of contrast enhanced ultrasound in the differential diagnosis of segmental testicular infarction.

Author

Peradejordi Font MR, Vas D, Trias Puigsureda I, Moreno Rojas JM, Ribal Caparrós MJ, and Nicolau Molina C

Abstract

A 43-year-old male presented to the emergency department with acute left testicular pain. Physical exam showed a tender left testicle and epididymis with mild swelling. Doppler and contrast enhanced ultrasound revealed a heterogeneous, avascular lesion with hyper vascularized surrounding. Follow-up contrast enhanced ultrasound performed a few days later showed persistence of the sparsely vascularized lesion with more hypoechoic echo structure. Despite the tumor markers being negative, a necrotic tumor could not be ruled out and a left orchiectomy was performed. Pathology report described an extensive segmental testicular infarction with no evidence of malignant tissue. We present the ultrasound and pathology findings, differential diagnostic pearls and clinical perspective of segmental testicular infarction., (© 2021 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Published
2021
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10. Clinical and radiological findings for small renal masses under active surveillance.

Author

Ajami T, Sebastia C, Corominas D, Ribal MJ, Nicolau C, Alcaraz A, and Musquera M

Subjects
Aged, Carcinoma, Renal Cell diagnostic imaging, Disease Progression, Female, Follow-Up Studies, Humans, Kidney Neoplasms diagnostic imaging, Male, Prognosis, Retrospective Studies, Carcinoma, Renal Cell pathology, Diagnostic Tests, Routine methods, Image Processing, Computer-Assisted methods, Kidney Neoplasms pathology, Tomography, X-Ray Computed methods, Watchful Waiting methods
Abstract

Objective: To analyze the experience performing active surveillance (AS) of small renal masses (SRMs) in our center and to correlate the evolution of SRMs under AS with clinical and radiological findings., Methods: Patients on AS between January 2012 until May 2020 for SRMs in our center have been included. Growth rate (GR) per year was analyzed and correlated with radiographic features. Patients with growth kinetics higher than 5mm/year during follow up were offered active treatment., Results: 73 patients were included in AS: the mean age was 75.7 years, a mean initial tumour size of 21.2 mm, and a mean growth rate of 2.05 mm/year. Around 60 % had an ASA score of 3. The tumor size did not change over time in 43% of cases; in 4% we noticed a regression in size and in 52% of cases growth during follow-up (38% 1-5mm/year and 14% more than 5 mm/year). Delayed active treatment was indicated in 16 (21%) of cases. Treatment applied was as following: 2 radiofrequency ablations, 6 radical and 8 partial nephrectomies. A weak correlation was found between initial size and growth rate (r = 0.38, P = 0.02). No significant association was detected regarding any of the analyzed radiological findings and GR. With a mean follow up time of 33 months none of the patients presented metastatic progression., Conclusion: Active surveillance is a feasible option for management of SRMs in selected patients without jeopardizing oncological safety. In our series, no clinical or radiological characteristics for predicting tumour growth were found., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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11. Evaluation of soils under the influence of coal mining and a thermoelectric plant in the city of Candiota and vicinity, Brazil.

Author

de Souza MR, Garcia ALH, Dalberto D, Nicolau C, Gazzineu AL, Grivicich I, Boaretto F, Picada JN, de Souza GMS, Chytry P, Dias JF, Corrêa DS, and da Silva J

Subjects
Animals, Brazil, Cell Line, Cities, Coal toxicity, Coal Mining methods, Comet Assay methods, Cricetulus, DNA Damage drug effects, Environmental Monitoring methods, Micronucleus Tests methods, Mutagenesis drug effects, Mutagens toxicity, Power Plants, Seasons, Coal analysis, Soil chemistry
Abstract

Coal burning generates gases, particles, and condensation by-products that are harmful to soil, water, and to the atmosphere. The aim of this study was to characterize and identify the cytotoxic and mutagenic potential of soil samples from the cities of Aceguá, Bagé, Candiota and Pinheiro Machado, near a large coal-fired power plant. Our study describes soil characteristics and contributes to the evaluation of the genotoxic activity of coal mining and burning, using the Comet Assay and Micronucleus test in V79 cells, as well as mutagenicity assays with Salmonella typhimurium strains. Comet Assay results show that the winter soil samples of Candiota and Pinheiro Machado induced a significant increase of the Damage Index for cells, as well as for the Aceguá summer sample. The micronucleus test did not detect differences between cities and seasons. A component analysis indicates associations between results obtained in Comet Assay and Ti and phenanthene concentrations for Pinheiro Machado during the winter, and Al for Aceguá during the summer and Zn during the winter. Results of Salmonella/microsome assays were negative, only Candiota and Pinheiro Machado samples showed a statistical increase of his + colonies in TA102. Our work describes biological data on these cells exposed to coal-contaminated soil, confirming the sensitivity of the Comet Assay in V79 cells and Salmonella/microsome assay for the evaluation of the effects of complex mixtures. These findings help to understand the spatial distribution of contaminants in the local soil related to a power plant, which is important for planning public safety actions., (Copyright © 2021. Published by Elsevier B.V.)

Published
2021
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12. Interprofessional and interdisciplinary collaboration for early phase oncological clinical trials in academia-Myo-inositoltrispyrophophate as model.

Author

Grossmann R, Schneider MA, Linecker M, Lehn JM, Nicolau C, Traber M, Tay F, Vicente D, Jetter A, Mollet A, Szucs T, Graf R, Clavien PA, and Limani P

Subjects
Animals, Humans, Antineoplastic Agents therapeutic use, Clinical Trials as Topic, Inositol Phosphates therapeutic use, Neoplasms drug therapy, Tumor Hypoxia drug effects
Published
2020
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13. Base excision repair (OGG1 and XRCC1) and metabolism (PON1) gene polymorphisms act on modulation of DNA damage and immune parameters in tobacco farmers.

Author

Kahl VFS, Simon D, de Souza MR, da Rosa VH, Nicolau C, Da Silva FR, Kvitko K, Peres A, Dorneles GP, de Souza CT, Dias JF, and Da Silva J

Subjects
Adult, Case-Control Studies, Farmers statistics & numerical data, Female, Humans, Interleukin-6 blood, Lymphocytes drug effects, Lymphocytes metabolism, Lymphocytes pathology, Male, Occupational Exposure adverse effects, Occupational Exposure analysis, Tumor Necrosis Factor-alpha blood, Aryldialkylphosphatase genetics, DNA Damage, DNA Glycosylases genetics, Inflammation Mediators blood, Polymorphism, Genetic, Nicotiana adverse effects, X-ray Repair Cross Complementing Protein 1 genetics
Abstract

Pesticides are one of the most frequently investigated chemical, due to their multiple uses in agricultural and public health areas. This study evaluates lymphocytes CBMN (cytokinesis-block micronucleus cytome assay), inflammatory markers, inorganic elements in blood samples, and the relationship of these parameters with XRCC1Arg194Trp, OGG1Ser326Cys and PON1Gln192Arg polymorphisms in a population of tobacco farmers. The study population comprised 129 agricultural workers exposed to pesticides and 91 nonexposed. Farmers had significantly increased NPB (nuclear plasmatic bridge), MN (micronucleus) and NBUD (nuclear bud) frequencies, as well as IL-6 (interleukin 6) and TNF-α (tumor necrosis factor alpha) serum levels, and decreased cytokines CD4+/CD8+ ratio. In the exposed group, XRCC1 Trp/- was correlated with decreased NDI (nuclear division index), and OGG1 Cys/- was associated with higher levels of NPB and decreased levels of IL-6. The combined effects of PON1 Arg/- and XRCC1 Arg/Arg were associated with increased NPB frequencies. In addition, the combination of PON1 Arg/- with XRCC1 Trp/- or OGG1 Cys/- influenced in increased levels of necrosis in farmers. Furthermore, tobacco farmers showed a positive correlation between TNF-α levels and NPB, CD4+/CD8+ ratio and NBUD; and IL-6 levels with both MN and NDI. The duration of years of work at tobacco fields was correlated positively with NBUD frequency. Sulfur, chlorine and potassium were found at increased levels in the exposed group when compared to the nonexposed one. These findings provide evidence that tobacco farmers' exposure have increased DNA damage and alter the immune system's response, and that XRCC1 and OGG1 polymorphisms could influence both biomarkers results., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Published
2018
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15. Magnetic resonance imaging of adenoma malignum of the uterine cervix with pathologic correlation: a case report.

Author

Castán Senar A, Paño B, Saco A, and Nicolau C

Abstract

Adenoma malignum (AM) is considered a rare subtype of cervical adenocarcinoma. Although previous reports have described magnetic resonance findings, none of these reports evaluated the utility of diffusion-weighted imaging in the differential diagnosis of AM and other multicystic cervical lesions. We present a case report of an AM that did not show restriction on the apparent diffusion coefficient map, which can be explained by the low cellularity of the tumor. This is consistent with the proper correlation between the diffusion imaging and histopathology of the tumor. In this way, AM can present with high apparent diffusion coefficient values, as in benign cervical lesions. Therefore, the combination of a solid multicystic lesion that invades the cervical stroma on T2-weighted magnetic resonance images and the absence of restriction on the apparent diffusion coefficient map are very suggestive of AM.

Published
2016
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16. Evaluation of regional hepatic perfusion (RHP) by contrast-enhanced ultrasound in patients with cirrhosis.

Author

Berzigotti A, Nicolau C, Bellot P, Abraldes JG, Gilabert R, García-Pagan JC, and Bosch J

Subjects
Adult, Blood Flow Velocity, Case-Control Studies, Catheterization, Female, Hepatic Veins diagnostic imaging, Humans, Liver Circulation, Liver Cirrhosis physiopathology, Male, Middle Aged, Phospholipids, Prospective Studies, Reproducibility of Results, Sulfur Hexafluoride, Ultrasonography, Contrast Media, Liver Cirrhosis diagnostic imaging, Microbubbles
Abstract

Background & Aims: Ultrasonographic contrast agents allow the assessment of myocardial and renal perfusion through the analysis of refill kinetics after microbubbles rupture. This study evaluated the feasibility of contrast-enhanced ultrasonographic (CEUS) estimations of regional hepatic perfusion in patients with cirrhosis, and its correlation with clinical and hemodynamic parameters., Methods: Fifty-five patients with cirrhosis undergoing hepatic vein catheterization were included. Hepatic perfusion was studied by CEUS (using Contrast Coherent Imaging) during a continuous i.v. infusion of microbubbles (SonoVue®); after their rupture (high insonation power), tissue refill was digitally recorded and time-intensity curves were electronically calculated on a region of interest of the right hepatic lobe. Regional hepatic perfusion (RHP) was calculated as microbubbles velocity×microbubble concentration. During hepatic vein catheterization, we measured hepatic blood flow by indocyanine green (ICG) infusion, hepatic venous pressure gradient (HVPG), and cardiac output (Swan-Ganz catheter)., Results: RHP was higher in patients than in healthy controls (5.1±3.7 vs. 3.4±0.7, p=0.003), and correlated with MELD (R=0.403, p=0.002), Child-Pugh score (R=0.348, p=0.009), and HVPG (R=0.279, p=0.041). RHP inversely correlated with ICG extraction (R=-0.346, p=0.039), ICG intrinsic clearance (R=-0.327, p=0.050), and ICG clearance (R=0.517, p=0.001), and directly correlated with hyperdynamic syndrome markers (cardiac index R=0.422, p=0.003; mean arterial pressure R=-0.405, p=0.004; systemic vascular resistance R=-0.496, p=0.001)., Conclusions: RHP increases in patients with cirrhosis and correlates with the degree of liver failure and hyperdynamic syndrome. RHP increases along with liver functional reserve decrease, suggesting that RHP increase occurs mainly through anatomical/functional shunts. RHP by CEUS is a feasible novel, objective, quantitative, non-invasive tool, potentially useful for the estimation of hepatic perfusion in patients with cirrhosis., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Published
2011
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17. [Prevalence of cardiovascular disease in uraemia and relevance of cardiovascular risk factors].

Author

Collado S, Coll E, Deulofeu R, Guerrero L, Pons M, Cruzado JM, de la Torre B, Vera M, Azqueta M, Nicolau C, and Cases A

Subjects
Aged, Aged, 80 and over, Arginine analogs & derivatives, Arginine blood, Biomarkers, Blood Proteins analysis, Cardiovascular Diseases blood, Cardiovascular Diseases diagnostic imaging, Comorbidity, Cross-Sectional Studies, Diabetes Complications epidemiology, Female, Humans, Hyperhomocysteinemia epidemiology, Hyperlipidemias epidemiology, Kidney Transplantation, Male, Middle Aged, Postoperative Complications epidemiology, Prevalence, Risk Factors, Smoking epidemiology, Stroke Volume, Ultrasonography, Uremia blood, Cardiovascular Diseases epidemiology, Uremia epidemiology
Abstract

Aim: To evaluate the prevalence of cardiovascular disease (CVD) and its association with cardiovascular risk factors, as well as their control in end-stage renal disease (ESRD) patients under maintenance hemodialysis (HD)., Patients and Methods: A total of 265 patients with ESRD on maintenance HD from a University Hospital and 4 dialysis units were included in this multicenter and cross-sectional study that analyzed the prevalence of CVD and the possible association with classic and new cardiovascular risk factors. Usual biochemical and haemathological parameters were analyzed, as well as plasma levels of homocysteine, troponin-I, BNP, lipoprotein(a), C reactive protein, IL-6, fibrinogen, asymmetrical dimethylarginine (ADMA), advanced oxidation protein products (AOPP), malondialdehyde, adiponectin, osteoprotegerin, and fetuin. In a subset of patients an echocardiography and carotid artery Doppler echography were also performed., Results: The prevalence of CVD was 52.8%. Factors positively associated with prevalent CVD were age, BMI, left ventricular hypertrophy, hypertension, dyslipidemia and diabetes mellitus, dialysis vintage, Charlson s comorbility index, levels of fibrinogen, osteoprotegerin, BNP and CRP, as well as carotid intima-media thickness, left ventricular mass and pulse pressure. Factors negatively associated with prevalent CVD were: previous renal transplant, ejection fraction or levels of LDL-c and phosphorous. In the multivariate analysis dyslipidemia, left ventricular hypertrophy, age and LDL-c (negatively) were associated with CVD., Conclusions: In HD patients the prevalence of CVD is high and is associated with the presence of cardiovascular risk factors and subclinical CVD.

Published
2010
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18. Induction of autoantibodies to murine P-glycoprotein: consequences on drug sensitivity in MDR cancer cells and on the expression of mdr genes in organs.

Author

Perrin L, Gatouillat G, Balasse E, Odot J, Nicolau C, Tosi PF, and Madoulet C

Subjects
ATP Binding Cassette Transporter, Subfamily B biosynthesis, ATP Binding Cassette Transporter, Subfamily B, Member 1 biosynthesis, ATP-Binding Cassette Transporters biosynthesis, Animals, Antibiotics, Antineoplastic pharmacology, Antineoplastic Agents, Phytogenic pharmacology, Cell Line, Tumor, Doxorubicin pharmacology, Female, Liposomes, Mice, Organ Specificity, Peptides immunology, Vinblastine pharmacology, ATP Binding Cassette Transporter, Subfamily B, Member 1 immunology, Autoantibodies biosynthesis, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Genes, MDR
Abstract

Overexpression of the 170 kDa plasma membrane P-glycoprotein (P-gp) represents the most common MDR mechanism in chemotherapy. In this work, specific autoantibodies to fragments from extracellular loops 1, 2, and 4 of the murine MDR1 P-gp were elicited in mice using synthetic palmitoylated peptides reconstituted in liposomes and alum. The highest IgG level was observed after the third immunization and the immune response against lipopeptides was still detected more than 200 days after immunizations. Immunocytochemichal studies revealed that these antibodies were specific for P-gp. When incubated with P-gp-expressing MDR cell lines, serum from immunized mice restored sensitivity to either doxorubicin or vinblastine, or had no effect in a cell type specific manner, suggesting that several mechanisms may occur in the establishment of the MDR phenotype. The expression of mdr1 and mdr3 genes was unchanged in organs from mice immunized with palmitoylpeptides grafted on liposomes. These results suggest that the induction of autoantibodies to P-gp is a safe strategy to overcome MDR in cancer chemotherapy.

Published
2007
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19. Human erythrocytes bearing electroinserted CD4 neutralize infection in vitro by primary isolates of human immunodeficiency virus type 1.

Author

Tosi PF, Schwartz D, Sharma U, Mouneimne Y, Hannig J, Li G, McKinley G, Grieco M, Flexner CW, Lazarte J, Norse D, Nicolau C, and Volsky DJ

Subjects
Acquired Immunodeficiency Syndrome blood, Binding, Competitive, CD4 Antigens genetics, Cells, Cultured, Coculture Techniques, Electroporation, Erythrocyte Membrane metabolism, HIV Core Protein p24 analysis, Humans, Kinetics, Recombinant Proteins metabolism, Virus Replication, CD4 Antigens metabolism, CD4-Positive T-Lymphocytes virology, Erythrocytes virology, HIV-1 physiology
Abstract

Human erythrocytes bearing electroinserted full-length CD4 (RBC-CD4) can bind and fuse with a laboratory strain of human immunodeficiency virus type 1 (HIV-1) or with T cells infected by HIV-1. Here we show that RBC-CD4 neutralize primary HIV-1 strains in an assay of cocultivation of peripheral blood mononuclear cells (PBMC) from HIV-1-infected persons with uninfected PBMC. RBC-CD4 inhibited viral p24 core antigen accumulation in these cocultures up to 10,000-fold compared with RBC alone. Viral p24 accumulation was inhibited equally well when measured in culture supernatants or in call extracts. The inhibition was dose-dependent and long-lived. Two types of recombinant CD4 tested in parallel were largely ineffective. The neutralization of primary HIV-1 by RBC-CD4 in vitro was demonstrated in PBMC cultures from 21 of a total of 23 patients tested at two independent sites. RBC-CD4 may offer a route to blocking HIV-1 infection in vivo.

Published
1996

20. Immune response against the murine mdri protein induced by vaccination with synthetic lipopeptides in liposomes.

Author

Tosi PF, Radu D, and Nicolau C

Subjects
Amino Acid Sequence, Animals, Autoantibodies immunology, Autoantibodies pharmacology, Doxorubicin metabolism, Doxorubicin pharmacology, Drug Resistance, Epitopes immunology, Leukemia L1210, Lipid A, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Palmitic Acid, Palmitic Acids immunology, Peptide Fragments chemistry, Peptide Fragments immunology, Tumor Cells, Cultured, ATP Binding Cassette Transporter, Subfamily B, Member 1 immunology, Autoantibodies blood, Immunization, Lipoproteins immunology, Liposomes
Abstract

Intrinsically, or after exposure to chemotherapeutic drugs, many cancer cells overexpress a class of high molecular weight membrane glycoproteins associated with the multidrug resistance (mdr) of these cells. This report describes an immunization protocol eliciting autoantibodies specific to extracellular epitopes of the murine mdr 1 P-glycoprotein (Pgp). Synthetic peptides with the sequences of extracellular loops of murine Pgp were covalently coupled with four palmitic acid moieties per peptide molecule. These "lipopeptides" were reconstituted in the bilayer of liposomes containing lipid A and used to immunize mice. Antibodies against the lipopeptides corresponding to loop 2 and 4 were elicited in sera of immunized mice. They reacted specifically with extracellular epitopes of the naturally occurring murine Pgp. After interaction with resistant cancer cells, the antibodies induced an average 50% increase in cellular accumulation of doxorubicin and Bodipy-verapamil. In the presence of these antibodies the resistance of L1210 mdr cells was reduced from an LD50 of 4 x 10(-5) M to 5 x 10(-7) M doxorubicin.

Published
1995
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21. Signal transduction in SF9 insect cells: endocytosis of recombinant CD4 after phorbol ester treatment.

Author

Grebenkämper K and Nicolau C

Subjects
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Animals, Antigens, CD biosynthesis, CD4 Antigens biosynthesis, Calmodulin antagonists & inhibitors, Cell Line, Cell Membrane immunology, Cell Membrane metabolism, Humans, Isoquinolines pharmacology, Kinetics, Piperazines pharmacology, Protein Kinase C antagonists & inhibitors, Recombinant Proteins biosynthesis, Recombinant Proteins metabolism, Spodoptera, Sulfonamides pharmacology, Time Factors, Transfection, Antigens, CD metabolism, CD4 Antigens metabolism, Endocytosis drug effects, Signal Transduction, Tetradecanoylphorbol Acetate pharmacology
Abstract

In Spodoptera frugiperda (Sf9) insect cells infected with a recombinant baculovirus carrying a gene construct encoding human CD4 endocytosis of CD4 is induced after stimulation with phorbol-12-myristate-13-acetate (PMA). Stimulation of endocytosis with PMA reduced the amount of full-length CD4 on the plasma membrane of Sf9 cells by 50% after 2 hours. Endocytosis of CD4 is blocked after intracellular delivery by cationic liposomes of a monoclonal antibody directed against a cytoplasmic sequence of CD4. Endocytosis is also blocked by the calmodulin inhibitor W7. The PKC inhibitor H7 does not inhibit PMA-induced endocytosis. A truncated CD4, in which the last 32 C-terminal amino acids were deleted did, not respond to PMA. Our results show that PMA can stimulate the calmodulin-dependent signal transduction for endocytosis of full-length CD4 in Sf9 cells. Phosphorylation of CD4 in Sf9 cells was not detectable after PMA treatment and PKC is not required for endocytosis.

Published
1995
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23. Electro-insertion of xeno-glycophorin into the red blood cell membrane.

Author

Mouneimne Y, Tosi PF, Gazitt Y, and Nicolau C

Subjects
Animals, Avidin, Biotin, Enzyme-Linked Immunosorbent Assay, Erythrocyte Membrane analysis, Fluorescein-5-isothiocyanate, Fluoresceins, Fluorescent Dyes, Glycophorins analysis, Humans, Mice, Microscopy, Fluorescence, Thiocyanates, Electricity, Erythrocyte Membrane metabolism, Glycophorins metabolism, Sialoglycoproteins metabolism
Abstract

The electroporation technique, with field strengths slightly below the critical value Ec for electroporation of red blood cells (RBC), enables the insertion of xeno-proteins into the RBC membrane without damaging the cells. The electro-insertion has been used to insert biotinylated human glycophorin into human RBC membrane and human glycophorin into murine RBC membrane. Binding anti-human glycophorin antibody (10F7) to the murine RBC bearing human glycophorin indicates extracellular orientation of inserted glycophorin. Insertion of about 10(5) glycophorin molecule per cell has been estimated by whole cell ELISA.

Published
1989
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