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1. Endothelial‐mesenchymal transition in skeletal muscle: Opportunities and challenges from 3D microphysiological systems

Author

Riccardo Francescato, Matteo Moretti, and Simone Bersini

Subjects
biofabrication, fibrosis, in vitro 3D modeling, organ‐on‐a‐chip, vascularization, Chemical engineering, TP155-156, Biotechnology, TP248.13-248.65, Therapeutics. Pharmacology, RM1-950
Abstract

Abstract Fibrosis is a pathological condition that in the muscular context is linked to primary diseases such as dystrophies, laminopathies, neuromuscular disorders, and volumetric muscle loss following traumas, accidents, and surgeries. Although some basic mechanisms regarding the role of myofibroblasts in the progression of muscle fibrosis have been discovered, our knowledge of the complex cell–cell, and cell–matrix interactions occurring in the fibrotic microenvironment is still rudimentary. Recently, vascular dysfunction has been emerging as a key hallmark of fibrosis through a process called endothelial‐mesenchymal transition (EndoMT). Nevertheless, no effective therapeutic options are currently available for the treatment of muscle fibrosis. This lack is partially due to the absence of advanced in vitro models that can recapitulate the 3D architecture and functionality of a vascularized muscle microenvironment in a human context. These models could be employed for the identification of novel targets and for the screening of potential drugs blocking the progression of the disease. In this review, we explore the potential of 3D human muscle models in studying the role of endothelial cells and EndoMT in muscle fibrotic tissues and identify limitations and opportunities for optimizing the next generation of these microphysiological systems. Starting from the biology of muscle fibrosis and EndoMT, we highlight the synergistic links between different cell populations of the fibrotic microenvironment and how to recapitulate them through microphysiological systems.

Published
2024
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2. Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

Author

Guillaume Pouessel, Claire Claverie, Julien Labreuche, Jean-Marie Renaudin, Aimée Dorkenoo, Mireille Eb, Anne Moneret-Vautrin, Antoine Deschildre, Stephane Leteurtre, Linus Grabenhenrich, Margitta Worm, Sabine Dölle, Kathrin Scherer, Isidor Hutteger, Morten Christensen, Carsten Bindslev-Jensen, Charlotte Mortz, Esben Eller, Henrik Fomsgaard Kjaer, Leonor Carneiro-Leão, Jenny Badas, Alice Coimbra, Dikla Pivko Levy, Moshe Ben-Shoshan, Ayelet Rimon, Shira Benor, Nicolette J. T. Arends, Nikki Edelbroek, Hans de Groot, Joyce A. M. Emons, H. Kim A. Brand, Dirk Verhoeven, Leonieke N. van Veen, Nicolette W. de Jong, Geunwoong Noh, Eun Ha Jang, Mariona Pascal, Olga Dominguez, Mònica Piquer, Montserrat Alvaro, Rosa Jimenez-Feijoo, Jaime Lozano, Adriana Machinena, Maria del Mar Folqué, Maria Teresa Giner, Ana María Plaza, Paul Turner, Nandinee Patel, Marta Vazquez-Ortiz, Sarah Lindsley, Lucy Walker, Simon Rosenberg, Adriano Mari, Claudia Alessandri, Ivana Giangrieco, Lisa Tuppo, Chiara Rafaiani, Georg Mitterer, Michela Ciancamerla, Rosetta Ferrara, Maria Livia Bernardi, Danila Zennaro, Maurizio Tamburrini, Maria Antonetta Ciardiello, Christian Harwanegg, Antonio Fernandez, Regina Selb, Philippe Egenmann, Michelle Epstein, Karin Hoffmann-Sommergruber, Frits Koning, Martinus Lovik, E. N. Clare Mills, Javier Moreno, Henk van Loveren, Jean-Michel Wal, Susanne Diesner, Cornelia Bergmayr, Barbara Pfitzner, Vera Elisabeth Assmann, Philipp Starkl, David Endesfelder, Thomas Eiwegger, Zsolt Szepfalusi, Heinz Fehrenbach, Erika Jensen-Jarolim, Anton Hartmann, Isabella Pali-Schöll, Eva Untersmayr, Soren Wille, Peter Meyer, Caroline Klingebiel, Jonas Lidholm, Angelica Ehrenberg, Jonas Östling, Isabelle Cleach, Jean-Louis Mège, Joana Vitte, Roberta Aina, Pawel Dubiela, Sabine Pfeifer, Merima Bublin, Christian Radauer, Piotr Humeniuk, Stefan Kabasser, Riccardo Asero, Gador Bogas, Francisca Gomez, Paloma Campo, Maria Salas, Inmaculada Doña, Esther Barrionuevo, Maria Auxiliadora Guerrero, Cristobalina Mayorga, Ana Prieto, Domingo Barber, Maria Jose Torres, Annette Jamin, Andrea Wangorsch, Barbara Ballmer, Stefan Vieths, Stephan Scheurer, Danijela Apostolovic, Jelena Mihailovic, Maja Krstic, Maria Starkhammar, Tanja Cirkovic Velickovic, Carl Hamsten, Marianne van Hage, Francine C. van Erp, Edward F. Knol, Hannah M. Kansen, Bo Pontoppidan, Yolanda Meijer, Cornelis K. van der Ent, André C. Knulst, Rebekah Sayers, Helen Brown, Adnan Custovic, Angela Simpson, Claire Mills, Juliane Schulz, Network for Online Registration of Anaphylaxis (NORA), Jaap Akkerdaas, Muriel Totis, Annabelle Capt, Corinne Herouet-Guicheney, Ronald van Ree, Tushar Banerjee, Antima Banerjee, Mathilde Claude, Grégory Bouchaud, Roberta Lupi, Laure Castan, Olivier Tranquet, Sandra Denery-Papini, Marie Bodinier, Chantal Brossard, Rosella De Poi, Elisa Gritti, Emiliano De Dominicis, Bert Popping, Patrizia Polverino de Laureto, Kati Palosuo, Anna Kaarina Kukkonen, Anna Pelkonen, Mika Mäkelä, Nanju Alice Lee, Johanna Rost, Sridevi Muralidharan, Dianne Campbell, Sam Mehr, Catherine Nock, Joseph Baumert, Steve Taylor, Carla Mastrorilli, Salvatore Tripodi, Carlo Caffarelli, Serena Perna, Andrea Di Rienzo Businco, Ifigenia Sfika, Arianna Dondi, Annamaria Bianchi, Carlotta Povesi Dascola, Giampaolo Ricci, Francesca Cipriani, Nunzia Maiello, Michele Miraglia del Giudice, Tullio Frediani, Simone Frediani, Francesco Macrì, Chiara Pistoletti, Iride Dello Iacono, Maria Francesca Patria, Elena Varin, Diego Peroni, Pasquale Comberiati, Loredana Chini, Viviana Moschese, Sandra Lucarelli, Roberto Bernardini, Giuseppe Pingitore, Umberto Pelosi, Roberta Olcese, Matteo Moretti, Anastasia Cirisano, Diego Faggian, Alessandro Travaglini, Mario Plebani, Maria Carmen Verga, Mauro Calvani, Paolo Giordani, Paolo Maria Matricardi, Noe Ontiveros, Francisco Cabrera-Chavez, Julie Galand, Etienne Beaudouin, The Anaphylaxis Working Group of the French Allergology SocietyThe Anaphylaxis Working Group of the French Allergology Society, Florence Pineau, Shinobu Sakai, Kayoko Matsunaga, Reiko Teshima, Colette Larré, Sandra Denery, Sebastian Tschirner, Valérie Trendelenburg, Gabriele Schulz, Bodo Niggemann, Kirsten Beyer, Youcef Bouferkas, Younes Belabbas, Djamel Saidi, Omar Kheroua, Kamel Eddine El Mecherfi, Malika Guendouz, Abir Haddi, Hanane Kaddouri, Luis Amaral, Ana Pereira, Susana Rodrigues, Mareen Datema, Laurian Jongejan, Michael Clausen, Andre Knulst, Nikolaos Papadopoulos, Marek Kowalski, Frédéric de Blay, Aeilko Zwinderman, Karin Hoffman-Sommergruber, Barbara Ballmer-Weber, Montserrat Fernandez-Rivas, Shan Deng, Jia Yin, Charlotte Eisenmann, Maria Nassiri, Rabea Reinert, Johanna P. M. van der Valk, Roy Gerth van Wijk, Yvonne Vergouwe, Ewout W. Steyerberg, Marit Reitsma, Harry J. Wichers, Huub F. J. Savelkoul, Berber Vlieg-Boerstra, Anthony E. J. Dubois, Fabrícia Carolino, Ana Rodolfo, Josefina Cernadas, Dasha Roa-Medellín, Ana Rodriguez-Fernandez, Joaquín Navarro, Vicente Albendiz, María Luisa Baeza, Sonsoles Intente-Herrero, Andrea Mikkelsen, Kirsten Mehlig, Lauren Lissner, Linda Verrill, Stefano Luccioli, Jolanda van Bilsen, Frieke Kuper, André Wolterbeek, Tanja Rouhani Rankouhi, Lars Verschuren, Hilde Cnossen, Prescilla Jeurink, Johan Garssen, Léon Knippels, Jossie Garthoff, Geert Houben, Winfried Leeman, M. Eleonore Pettersson, Afke M. M. Schins, Gerard H. Koppelman, Boudewjin J. Kollen, Svitlana Zubchenko, Sarah Kuntz, Pablo Mérida, Montserrat Álvaro, Monica Piquer, Carmen Riggioni, Juan Heber Castellanos, Rosa Jimenez, Melanie Cap, Elodie Drumez, Stéphanie Lejeune, Caroline Thumerelle, Clémence Mordacq, Véronique Nève, Sonia Ricò, Margherita Varini, Rita Nocerino, Linda Cosenza, Antonio Amoroso, Margherita Di Costanzo, Carmen Di Scala, Giorgio Bedogni, Roberto Berni Canani, Paul J. Turner, Paloma Poza-Guedes, Ruperto González-Pérez, Inmaculada Sánchez-Machín, Victor Matheu-Delgado, Erik Wambre, Anne-Sofie Ballegaard, Charlotte Madsen, Juliane Gregersen, Katrine Lindholm Bøgh, Philippe Aubert, Michel Neunlist, Antoine Magnan, Daniel Lozano-Ojalvo, Alba Pablos-Tanarro, Leticia Pérez-Rodríguez, Elena Molina, Rosina López-Fandiño, Akila Rekima, Patricia Macchiaverni, Mathilde Turfkruyer, Sebastien Holvoet, Lénaïck Dupuis, Nour Baiz, Isabella Annesi-Maesano, Annick Mercenier, Sophie Nutten, Valérie Verhasselt, Ines Mrakovcic-Sutic, Srdan Banac, Ivana Sutic, Zdenka Baricev-Novakovic, Ingrid Sutic, Valentino Pavisic, Rosa Muñoz-Cano, Teodoríkez Jiménez-Rodríguez, Daniel Corbacho, Jordi Roca-Ferrer, Joan Bartra, Aleksandar Bulog, Vladimir Micovic, Lidia Markiewicz, Agata Szymkiewicz, Anna Szyc, Barbara Wróblewska, Bryan M. Harvey, Lucien F. Harthoorn, A. Wesley Burks, Georgios Rentzos, Anna-Lena Bramstång Björk, Ulf Bengtsson, Colin Barber, Chrystyna Kalicinsky, Christine Breynaert, Lieve Coorevits, Cornelia Jansen, Erna Van Hoeyveld, Kristin Verbeke, Anne-Marie Kochuyt, Rik Schrijvers, Diana Deleanu, Adriana Muntean, Maria Konstantakopoulou, Maria Pasioti, Anastasia Papadopoulou, Anna Iliopoulou, Nikolaos Mikos, Evangelia Kompoti, Eunice Dias de Castro, Borja Bartalomé, Kok Loong Ue, Elizabeth Griffiths, Stephen Till, Kate Grimshaw, Graham Roberts, Anna Selby, Indre Butiene, Jose Ignacio Larco, Ruta Dubakiene, Ana Fiandor, Alessandro Fiocchi, Nikos Papadopoulos, Sigurveig Sigurdardottir, Aline Sprikkelman, Anne-Fleur Schoemaker, Paraskevi Xepapadaki, Thomas Keil, Zizi Cojocariu, Beatriz Secades Barbado, Vasti Iancu, Esozia Arroabarren, Marta Goñi Esarte, Miren Arteaga, Mayra Coutinho Andrade, Denise Borges, Jorge Kalil, Pedro Giavina Bianchi, Rosana Camara Agondi, Rinkesh Kumar Gupta, Akanksha Sharma, Kriti Gupta, Mukul Das, Premendra Dwivedi, Rusudan Karseladze, Liana Jorjoliani, Lali Saginadze, Mariam Tskhakaia, Katia Basello, Gabriele Piuri, Attilio Francesco Speciani, Michela Carola Speciani, Carla Camerotto, Francesco Zinno, Olga Pakholchuk, Svitlana Nedelska, Stefano Pattini, Maria Teresa Costantino, Silvia Peveri, Danilo Villalta, Eleonora Savi, Andrea Costanzi, Vera A. Revyakina, Marina A. Kiseleva, Elena D. Kuvshinova, Inna A. Larkova, Anton A. Shekhetov, Diana Silva, André Moreira, José Plácido, Hanneke van der Kleij, Esther van Twuijver, Robbert Sutorius, Pieter-Jan de Kam, Jenny van Odijk, Helen Lindqvist, Elin Lustig, Amyra Ali Azamar Jácome, Karla Leversia Borjas Aguilar, Miguel García Domínguez, David Alejandro Mendoza Hernández, Cristiano Caruso, Cono Casale, Gian Lodovico Rapaccini, Antonino Romano, Italo De Vitis, Renata R. Cocco, Carolina Aranda, Marcia C. Mallozi, Jackeline F. Motta, Lilian Moraes, Antonio Pastorino, Nelson Rosario, Ekaterini Goudouris, Arnaldo Porto, Neusa F. Wandalsen, Emanuel Sarinho, Flavio Sano, Dirceu Solé, Constantinos Pitsios, Maria Petrodimopoulou, Ekaterini Papadopoulou, Maria Passioti, Meropi Kontogianni, Nino Adamia, Ekaterina Khaleva, Ana Prieto del Prado, George Du Toit, Edyta Krzych, Urszula Samolinska-Zawisza, Konrad Furmanczyk, Aneta Tomaszewska, Filip Raciborski, Agnieszka Lipiec, Piotr Samel-Kowalik, Artur Walkiewicz, Jacek Borowicz, Boleslaw Samolinski, Aimee Lou Nano, Marysia Recto, Maria Luisa Somoza, Natalia Blanca López, Diana Pérez Alzate, Francisco Javier Ruano, Maria Isabel Garcimartín, Elisa Haroun, Maria Vázquez de la Torre, Antonia Rojas, Montserrat López Onieva, Gabriela Canto, Alexandra Rodrigues, Andreia Forno, António Jorge Cabral, Rute Gonçalves, Ilya Vorozhko, Tatyana Sentsova, Olga Chernyak, Svetlana Denisova, Lidia Ilènko, Valery Muhortnich, Caroline Zimmermann, Alexander Rohrbach, Faisal R. Bakhsh, Kollen Boudewijn, Anne-Marie Oomkes-Pilon, Dorien Van Ginkle, Mira Šilar, Anja Jeverica, Tina Vesel, Tadej Avčin, Peter Korošec, Johanna van der Valk, Irene Berends, Nicolette Arends, Maurits van Maaren, Harry Wichers, Joyce Emons, Anthony Dubois, Nicolette de Jong, Oksana Matsyura, Lesya Besh, Chung-Hsiung Huang, Tong-Rong Jan, Gary Stiefel, Jean Tratt, Kerrie Kirk, Fabricia Carolino, Stefania Arasi, Lucia Caminiti, Giuseppe Crisafulli, Chiara Fiamingo, Jlenia Fresta, Giovanni Pajno, Ben Remington, Astrid Kruizinga, W. Marty Blom, Joost Westerhout, Sabina Bijlsma, Joe Baumert, Mark Blankestijn, Henny Otten, Rob Klemans, Anouska D. Michelsen-Huisman, Harmieke van Os-Medendorp, Astrid G. Kruizinga, Astrid Versluis, Gert van Duijn, H. Mary-Lene de Zeeuw-Brouwer, Jacqueline J. M. Castenmiller, Hub P. J. M. Noteborn, Geert F. Houben, Kristian Bravin, David Luyt, Bushra Javed, Phil Couch, Christopher Munro, Phil Padfield, Matt Sperrin, Aideen Byrne, Lizalet Oosthuizen, Carina Kelleher, Fiona Ward, Niamh Brosnan, Graham King, Eva Corbet, Josué Alejandro Huertas Guzmán, Montserrat Bosque García, Oscar Asensio, Laura Valdesoiro Navarrete, Helena Larramona, Xavier Domingo Miró, Katarzyna Pyrz, Moira Austin, Yanne Boloh, Philip Couch, Deirdre Galloway, Pilar Hernandez, Jonathan O’B. Hourihane, Fiona Kenna, Barbara Majkowska-Wojciechowska, Lynne Regent, Marina Themisb, Sabine Schnadt, Aida Semic-Jusufagic, Audrey Dunn Galvin, Tiina Kauppila, Mikael Kuitunen, Nikolaos A. Kitsioulis, Nikolaos Douladiris, Sofia Kostoudi, Ioanna Manolaraki, Dimitris Mitsias, Emmanouil Manousakis, Nikolaos G. Papadopoulos, Rebecca Knibb, Jennifer Hammond, Richard Cooke, Jaakko Yrjänä, Anna-Maija Hanni, Päivi Vähäsarja, Oona Mustonen, Teija Dunder, Petri Kulmala, Eva Lasa, Carmen D’Amelio, Sara Martínez, Alejandro Joral, Gabriel Gastaminza, Maria Jose Goikoetxea, David C. A. Candy, Marleen T. J. Van Ampting, Manon M. Oude Nijhuis, Assad M. Butt, Diego G. Peroni, Adam T. Fox, Jan Knol, Louise J. Michaelis, Ines Padua, Patricia Padrao, Pedro Moreira, Renata Barros, Hanan Sharif, Manzoor Ahmed, Nehad Gomaa, Joris Mens, Koen Smit, Frans Timmermans, Tomaž Poredoš, Anja Koren Jeverica, Marjeta Sedmak, Evgen Benedik, Meta Accetto, Mirjana Zupančič, Glauce Yonamine, Gustavo Soldateli, Bruna Aquilante, Antonio Carlos Pastorino, Cleonir Lui de Moraes Beck, Andrea Keiko Gushken, Mayra de Barros Dorna, Cristiane Nunes dos Santos, Ana Paula Moschione Castro, Abdulhadi Al-Qahtani, Rand Arnaout, Agha Rehan Khaliq, Rashid Amin, Farrukh Sheikh, Jorge Alvarez, Marta Anda, Miriam Palacios, Montserrat De Prada, Carmen Ponce, Bianca Balbino, Riccardo Sibilano, Thomas Marichal, Nicolas Gaudenzio, Hajime Karasuyama, Pierre Bruhns, Mindy Tsai, Laurent L. Reber, Stephen J. Galli, Ana Reis Ferreira, Josefina R. Cernadas, Aida del Campo García, Sara Pereiro Fernández, Nerea Sarmiento Carrera, Fernando Bandrés Sánchez-Cruz, José Ramón Fernández Lorenzo, Stephanie Claus, Claudia Pföhler, Franziska Ruëff, Regina Treudler, Mercedes Escarrer Jaume, Agustin Madroñero, Maria Teresa Guerra Perez, Juan Carlos Julia, Charlotte Hands Plovdiv, Lee Gethings, Jim Langridge, Karine Adel-Patient, Hervé Bernard, Ivona Barcievic-Jones, Raditsa Sokolova, Rumyana Yankova, Mariya Ivanovska, Marianna Murdjeva, Tatyana Popova, Svetlan Dermendzhiev, Martin Karjalainen, Ulrike Lehnigk, Duncan Brown, Julie C. Locklear, Julie Locklear, Ioana Maris, Jonathan Hourihane, Cristina Ornelas, Joana Caiado, Manuel Branco Ferreira, Manuel Pereira-Barbosa, Yolanda Puente, Juan Carlos Daza, Francisco Javier Monteseirin, Natalia Ukleja-Sokolowska, Ewa Gawronska-Ukleja, Magdalena Zbikowska-Gotz, Zbigniew Bartuzi, Lukasz Sokolowski, Aine Adams, Bernard Mahon, Karen English, Nelly Gourdon-Dubois, Laetitia Sellam, Bruno Pereira, Elodie Michaud, Khaled Messaoudi, Bertrand Evrard, Jean-Luc Fauquert, Francisca Palomares, Gador Gomez, Maria Jose Rodriguez, Luisa Galindo, Ana Molina, Lorella Paparo, Maurizio Mennini, Rosita Aitoro, Adam Wawrzeńczyk, Michał Przybyszewski, Anna Wawrzeńczyk, Hulya Ercan Sarıcoban, Meltem Ugras, Zerrin Yalvac, Bertine M. J. Flokstra-de Blok, J. L. van der Velde, Andrea Vereda, Clara Ippolito, Amaranta Traversa, Daniela Adriano, Daniela Manila Bianchi, Silvia Gallina, Lucia Decastelli, Melina Makatsori, Anne Miles, Sonja Posega Devetak, Iztok Devetak, Soraya Ainad Tabet, Jeanette Fisker Trandbohus, Pernille Winther, Hans-Jørgen Malling, Kirsten Skamstrup Hansen, Lene Heise Garvey, Chia-Chi Wang, Yin-Hua Cheng, Chun-Wei Tung, Mariola Dietrich, Ingo Marenholz, Birgit Kalb, Sarah Grosche, Katharina Blümchen, Rupert Schlags, Mareike Price, Sylke Rietz, Jorge Esparza-Gordillo, Susanne Lau, Young-Ae Lee, Ali Almontasheri, Mohammad Al Bahkali, Sahar Elshorbagi, Abdullah Alfhaid, Mashary Altamimi, Eman Madbouly, Hassan Al-Dhekri, Rand K. Arnaout, Maria Basagaña, Sira Miquel, Borja Bartolomé, Bettina Brix, Stefanie Rohwer, Sandra Brandhoff, Alena Berger, Waltraud Suer, Alf Weimann, Cristina Bueno, Laura Martín-Pedraza, Sara Abián, Pablo San Segundo-Acosta, Juan Carlos López-Rodríguez, Rodrigo Barderas, Eva Batanero, Javier Cuesta-Herranz, María Teresa Villalba, Magna Correia, Filipe Benito-Garcia, Cristina Arêde, Susana Piedade, Mário Morais-Almeida, James Hindley, Ross Yarham, Anna Kuklinska-Pijanka, David Gillick, Karine Patient, Martin D. Chapman, Katrine L. Bøgh, Ana Miranda, Eugénia Matos, Anna Sokolova, Huan Rao, Ivona Baricevic-Jones, Frances Smith, Wentong Xue, Helga Magnusdottir, Anna G. Vidarsdottir, Sigrun Lund, Anders Blom Jensen, Bjorn R. Ludviksson, Reyna Simon, Robert Elfont, Sean Bennett, Robert Voyksner, Maria de Lurdes Torre, Songül Yürek, Margaretha A. Faber, Annick Bastiaensen, Evelyne Mangodt, Athina van Gasse, Ine Decuyper, Vito Sabato, Margo M. Hagendorens, Chris H. Bridts, Luc S. De Clerck, Didier Ebo, Susanne Schwarz, Mandy Ziegert, Saskia Albroscheit, Christian Schwager, Skadi Kull, Jochen Behrends, Niels Röckendorf, Frauke Schocker, Andreas Frey, Arne Homann, Wolf-Meinhard Becker, Uta Jappe, Nesrine Zaabat, Sylvia Osscini, Chantal Agabriel, Benoît Sterling, Ania Carsin, Valérie Liabeuf, Monica Maćków, Alina Zbróg, Monica Bronkowska, Justine Courtois, Romy Gadisseur, Catherine Bertholet, Pierre Lukas, Etienne Cavalier, Philippe Delahaut, Birgit Quinting, Margareta Brandt Gertmo, Ewa Ternesten Hasseus, Vladyslava Barzylovych, Júlio Oliveira, Luis F. Ensina, Carolina S. Aranda, Leire Dopazo, Rebeca Lopez, Raquel Perez, Laura Santos-Diez, Agurtzane Bilbao, Juan Miguel Garcia, Ignacio García Núñez, María Ángeles Algaba Mármol, María José Barasona Villarejo, José Antonio Bácter Martos, Marina Suárez Vergara, José María Ignacio García, Agata Michalska, Grzegorz Sergiejko, Robert Zacniewski, Ileana-Maria Ghiordanescu, Cristina Deaconu, Mihaela Popescu, Roxana Silvia Bumbacea, Alkerta Ibranji, Elida Nikolla, Gjustina Loloci, Nanna Juel-Berg, Lau Fabricius Larsen, Lars Kjaergaard Poulsen, João Marcelino, Ricardo Prata, Ana Célia Costa, Fátima Duarte, Marta Neto, Jennifer Santos, Luís Câmara Pestana, Daniel Sampaio, Paola Minale, Paola Dignetti, Donatella Bignardi, Irena Nedelea, Florin-Dan Popescu, Mariana Vieru, Florin-Adrian Secureanu, Carmen Saviana Ganea, Miguel Vieira, José Pedro Moreira Silva, Timothy Watts, Sophia Watts, Marta Lomikovska, Marina Peredelskaya, Natalia Nenasheva, Ivana Filipovic, Zorica Zivkovic, Djordje Filipovic, Jennette Higgs, Amena Warner, and Carla Jones

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2017
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3. Ethyl glucuronide in hair: A 5‐year retrospective cohort study in subjects sanctioned for driving under the influence of alcohol and psychoactive substances

Author

Francesca Freni, Matteo Moretti, Sara Scardo, Claudia Carelli, Claudia Vignali, Maria Cristina Monti, and Luca Morini

Subjects
Male, Adolescent, Alcohol Drinking, Ethanol, Pharmaceutical Science, Glucuronates, Middle Aged, Analytical Chemistry, Humans, Environmental Chemistry, Female, Driving Under the Influence, Biomarkers, Spectroscopy, Hair, Retrospective Studies
Abstract

The evaluation of drinking behaviors can help in limiting high-risk situation, such as driving under the influence (DUI). We investigate ethyl glucuronide in hair (hEtG) levels to evaluate alcohol consumption behavior in subjects followed up after having been charged for DUI of psychoactive substances and/or alcohol. We performed a retrospective observational cohort study on 4328 subjects over 18 years old who underwent hEtG analysis in the period 2015-2019 in the Italian Province of Pavia. hEtG level was used as a proxy for the alcohol consumption behavior. Effects of age, sex, and district on alcohol drinking behavior were investigated with an ordinal logit model. A state sequence analysis was used to study people's alcohol consumption behavior over time. hEtG was found ≥7.0 pg/mg in 22.2% of the drivers (of which 7% has an hEtG ≥30.0 pg/mg). Among positive cases, a prevalence of males (96.3%) aged 35-44 (32.6%), coming from main city and hinterland (38.2%), was observed. The propensity to drink was higher for males (odds ratio [OR] ≈ 2.28, p 0.001) and for subject coming from the district devoted to the cultivation of vineyards. Young age classes have a reduced drinking risk if compared to the drivers over 55 years old (p 0.001). A general decreasing trend over time in hEtG values was observed. Being male, age ≥ 55 years, and coming from rural areas are potential risk factors related to alcohol drinking habits among drivers. Ethyl glucuronide in hair test in the driving license reissuing protocol contributed to decrease alcohol misuse behaviors.

Published
2022
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4. Genetic individual identification from dried urine spots: A complementary tool to drug monitoring and anti‐doping testing

Author

Pierangela Grignani, Alessandro Manfredi, Maria Cristina Monti, Matteo Moretti, Luca Morini, Silvia Damiana Visonà, Paolo Fattorini, Carlo Previderè, Grignani, Pierangela, Manfredi, Alessandro, Monti, Maria Cristina, Moretti, Matteo, Morini, Luca, Visonà, Silvia Damiana, Fattorini, Paolo, and Previderè, Carlo

Subjects
Male, drug monitoring, DUS, STR, genetic identification, urine manipulation, Reproducibility of Results, Pharmaceutical Science, Body Fluids, Specimen Handling, Analytical Chemistry, Humans, Environmental Chemistry, Female, Dried Blood Spot Testing, Drug Monitoring, Spectroscopy
Abstract

The collection of liquid biological matrices onto paper cards (dried matrix spots [DMS]) is becoming an alternative sampling strategy. The stability over time of molecules of interest for therapeutic, sport drug monitoring, and forensic toxicology on DMS has been recently investigated representing a reliable alternative to conventional analytical techniques. When a tampering of a urine sample in drug monitoring or doping control cases is suspected, it could be relevant to know whether genetic profiles useful for individual identification could be generated from urine samples spotted onto paper (dried urine spot [DUS]). To understand the influence of sex, storage conditions, and time on the quality and quantity of the DNA, five female and ten male urine samples were dispensed onto Whatman 903 paper and sampled after different storage conditions over time, from 1 to 12 weeks. Direct PCR was performed starting from 2-mm punches collected from each spot amplifying a panel of markers useful for individual identification. The female DUS stored in different conditions produced genetic profiles fully matching the reference samples. The same result was obtained for the male DUS but using urine 30X concentrated by centrifugation instead of the original samples. Our data show that this approach is valid for genetic individual identification of urine samples spotted onto paper cards up to 12 weeks after deposition and could be easily incorporated in anti-doping or drug screening protocols to help on the suspicion of evidence tampering or to solve questions on the reliability of samples collection.

Published
2022
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6. A liquid chromatography-tandem mass spectrometry method for the determination of cocaine and metabolites in blood and in dried blood spots collected from postmortem samples and evaluation of the stability over a 3-month period

Author

Angelo Groppi, Antonio Marco Maria Osculati, Ilaria Tomaciello, Luca Tajana, Luca Morini, Matteo Moretti, Silvia Damiana Visonà, Francesca Freni, and Claudia Vignali

Subjects
Pharmaceutical Science, Tandem mass spectrometry, 030226 pharmacology & pharmacy, 01 natural sciences, Analytical Chemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cocaethylene, Cocaine, Limit of Detection, Tandem Mass Spectrometry, Liquid chromatography–mass spectrometry, medicine, Humans, Environmental Chemistry, Solid phase extraction, Chromatography, High Pressure Liquid, Spectroscopy, Dried Blood Spot Testing, Detection limit, Chromatography, Solid Phase Extraction, 010401 analytical chemistry, Reproducibility of Results, 0104 chemical sciences, Dried blood spot, chemistry, Benzoylecgonine, Autopsy, medicine.drug
Abstract

The aims of this study were (1) to identify and quantify cocaine (COC), benzoylecgonine (BE), ecgonine methyl ester (EME), and cocaethylene (CE) in DBS; (2) to compare dried blood spots (DBSs) analytical results with the routine blood analyses; (3) to monitor analytes stability on DBS within a 3-month period. Eighty-five μL of blood from postmortem cases were put on a card for DBS analysis and kept in the dark, at room temperature. Samples were extracted through solid-phase extraction (SPE) cartridges and injected in the liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. The analytical procedure is simple, sensitive, and specific. Limits of detection (LODs) and quantification (LOQs) were calculated at 1.0 and 5.0 ng/mL(g) for COC and CE, and at 0.5 and 2 ng/mL for EME and BE, respectively. Validation parameters fulfilled all the acceptance criteria. Fifty-five postmortem cases were evaluated. Eighteen cases were positive for COC (44-2456 ng/mL) and BE (228-4700 ng/mL), 12 for EME (92-1500 ng/mL), and 11 cases for CE (11-273 ng/mL). Stability was evaluated on 8 cases collected in the period January 2017-January 2018. For each case, 5 DBSs were collected at T0. Four DBSs were analyzed within the 4 following weeks and 1 sample was analyzed after 3 months. The concentrations on DBSs, stored at room temperature, always matched the ones obtained on blood samples kept at -20°C (

Published
2018
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7. Rational Design of Prevascularized Large 3D Tissue Constructs Using Computational Simulations and Biofabrication of Geometrically Controlled Microvessels

Author

Matteo Moretti, Junji Fukuda, Matilde Bongio, Simone Bersini, Chiara Arrigoni, Giuseppe Talò, and Junko Enomoto

Subjects
Vascular Endothelial Growth Factor A, 0301 basic medicine, Materials science, VEGF receptors, Shear force, Biomedical Engineering, Pharmaceutical Science, 02 engineering and technology, Biomaterials, 03 medical and health sciences, Tissue engineering, Angiopoietin-1, Human Umbilical Vein Endothelial Cells, Bioreactor, Humans, Computer Simulation, Cell Line, Transformed, Tissue Engineering, Tissue Scaffolds, biology, technology, industry, and agriculture, Rational design, Hydrogels, Mesenchymal Stem Cells, 021001 nanoscience & nanotechnology, 030104 developmental biology, Vascular network, Microvessels, Self-healing hydrogels, biology.protein, 0210 nano-technology, Biofabrication, Biomedical engineering
Abstract

A major challenge in the development of clinically relevant 3D tissue constructs is the formation of vascular networks for oxygenation, nutrient supply, and waste removal. To this end, this study implements a multimodal approach for the promotion of vessel-like structures formation in stiff fibrin hydrogels. Computational simulations have been performed to identify the easiest microchanneled configuration assuring normoxic conditions throughout thick cylindrical hydrogels (8 mm height, 6 mm ∅), showing that in our configuration a minimum of three microchannels (600 μm ∅), placed in a non-planar disposition, is required. Using small hydrogel bricks with oxygen distribution equal to the microchanneled configuration, this study demonstrates that among different culture conditions, co-culture of mesenchymal and endothelial cells supplemented with ANG-1 and VEGF leads to the most developed vascular network. Microchanneled hydrogels have been then cultured in the same conditions both statically and in a bioreactor for 7 d. Unexpectedly, the combination between shear forces and normoxic conditions is unable to promote microvascular networks formation in three-channeled hydrogels. Differently, application of either shear forces or normoxic conditions alone results in microvessels outgrowth. These results suggest that to induce angiogenesis in engineered constructs, complex interactions between several biochemical and biophysical parameters have to be modulated.

Published
2016
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8. Fabrication of multi-well chips for spheroid cultures and implantable constructs through rapid prototyping techniques

Author

Alessia Di Giancamillo, Francesco Piraino, Giuseppe M. Peretti, Marco Rasponi, Matteo Moretti, Raymond J. Kemp, Silvia Lopa, Arianna B. Lovati, Lorenzo Moroni, and Clelia Di Caro

Subjects
Cell type, Polydimethylsiloxane, Cell, Spheroid, Bioengineering, Nanotechnology, Chondrogenesis, Applied Microbiology and Biotechnology, Glycosaminoglycan, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Tissue engineering, In vivo, medicine, Biotechnology, Biomedical engineering
Abstract

Three-dimensional (3D) culture models are widely used in basic and translational research. In this study, to generate and culture multiple 3D cell spheroids, we exploited laser ablation and replica molding for the fabrication of polydimethylsiloxane (PDMS) multi-well chips, which were validated using articular chondrocytes (ACs). Multi-well ACs spheroids were comparable or superior to standard spheroids, as revealed by glycosaminoglycan and type-II collagen deposition. Moreover, the use of our multi-well chips significantly reduced the operation time for cell seeding and medium refresh. Exploiting a similar approach, we used clinical-grade fibrin to generate implantable multi-well constructs allowing for the precise distribution of multiple cell types. Multi-well fibrin constructs were seeded with ACs generating high cell density regions, as shown by histology and cell fluorescent staining. Multi-well constructs were compared to standard constructs with homogeneously distributed ACs. After 7 days in vitro, expression of SOX9, ACAN, COL2A1, and COMP was increased in both constructs, with multi-well constructs expressing significantly higher levels of chondrogenic genes than standard constructs. After 5 weeks in vivo, we found that despite a dramatic size reduction, the cell distribution pattern was maintained and glycosaminoglycan content per wet weight was significantly increased respect to pre-implantation samples. In conclusion, multi-well chips for the generation and culture of multiple cell spheroids can be fabricated by low-cost rapid prototyping techniques. Furthermore, these techniques can be used to generate implantable constructs with defined architecture and controlled cell distribution, allowing for in vitro and in vivo investigation of cell interactions in a 3D environment.

Published
2015
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9. Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

Author

Georgios Rentzos, Esben Eller, Annick Mercenier, Magna Correia, Pedro Moreira, Linda Verrill, Mário Morais-Almeida, Frauke Schocker, Carsten Bindslev-Jensen, Ulrike Lehnigk, Andreas Frey, Lars Verschuren, Anna-Lena Bramstång Björk, Lene Heise Garvey, Elena Molina, Katrine L. Bøgh, J. L. van der Velde, Montserrat Alvaro, Phil Padfield, Niamh Brosnan, Nelly Gourdon-Dubois, Christian Harwanegg, Manuel Branco Ferreira, Songül Yürek, Amyra Ali Azamar Jácome, Rashid Amin, José Ramón Fernández Lorenzo, Kirsten Beyer, Florin-Adrian Secureanu, Charlotte Bernhard Madsen, Julie Galand, Claudia Pföhler, Rabea Reinert, Heinz Fehrenbach, Anton Hartmann, Maria Salas, Arne Homann, Rand Arnaout, Sarah Lindsley, Nerea Sarmiento Carrera, Patrícia Padrão, Berber Vlieg-Boerstra, Alkerta Ibranji, Benoît Sterling, Maria Auxiliadora Guerrero, Maria L. Baeza, Maurizio Tamburrini, Eva Untersmayr, Tanja Cirkovic Velickovic, Farrukh Sheikh, Sarah Kuntz, Sara Martínez, Kriti Gupta, Maria de Lurdes Torre, Yvonne Vergouwe, Ross Yarham, Faisal R. Bakhsh, Marta Vazquez-Ortiz, João Marcelino, Tullio Frediani, Ricardo Prata, Anna Kaarina Kukkonen, Gustavo Soldateli, Ines Mrakovčić-Šutić, Elodie Drumez, Cristina Ornelas, Maria Vazquez de La Torre, Renata Barros, Agata Szymkiewicz, Aneta Tomaszewska, Stefanie Rohwer, Charlotte Eisenmann, Adriana Muntean, Matteo Moretti, Johanna P. M. van der Valk, Birgit Quinting, Stefan Kabasser, David Gillick, Michał Przybyszewski, Grzegorz Sergiejko, Antonio Jorge Cabral, Alba Pablos-Tanarro, Robert Elfont, Marit Reitsma, Roxana Silvia Bumbăcea, Nelson Rosario, Maria Livia Bernardi, Cristiane N. Santos, Christian Radauer, Sandra Denery-Papini, Geert F. Houben, Nicolette W. de Jong, Marta Anda, Alexander Rohrbach, Teodorikez Wilfox Jimenez-Rodriguez, María Teresa Villalba, Karine Patient, Harmieke van Os-Medendorp, Kathrin Scherer, Marta Goñi Esarte, Svetlan Dermendzhiev, Jossie Garthoff, Michelle M. Epstein, Catherine Bertholet, Bruna Pultrini Aquilante, Didier G. Ebo, Roberta Aina, Jorge Kalil, Petri Kulmala, Lars K. Poulsen, Barbara Ballmer, H. Mary-Lene de Zeeuw-Brouwer, Karin Hoffman-Sommergruber, Winfried Leeman, Anne Miles, Nehad Gomaa, Maria Teresa Costantino, Evelyne Mangodt, Maria Konstantakopoulou, Rosa Jimenez, Attilio Francesco Speciani, Helga Magnusdottir, Inmaculada Sánchez-Machín, H. Kaddouri, Raquel Perez, Astrid Versluis, Anthony E. J. Dubois, Anja Koren Jeverica, Zdenka Barićev-Novaković, Joost Westerhout, A.M. Plaza, Júlio Oliveira, Pierre Lukas, Oksana Matsyura, Giuseppe Pingitore, Mira Silar, Huub F. J. Savelkoul, Urszula Samolinska-Zawisza, Chantal Brossard, Ana Reis Ferreira, Reiko Teshima, Serena Perna, Mariola Dietrich, Dirk Verhoeven, Fiona Kenna, Paloma Poza-Guedes, Cristobalina Mayorga, Pilar Hernandez, Roberto Bernardini, Roberto Berni Canani, Maria Francesca Patria, Mariana Vieru, Julie Locklear, Esther van Twuijver, Marina A. Kiseleva, H. Kim A. Brand, Gabriele Schulz, Ileana-Maria Ghiordanescu, Nikolaos G. Papadopoulos, Danijela Apostolovic, Maria del Mar Folqué, Eva Lasa, Mohammad Al Bahkali, Arianna Dondi, Sofia Kostoudi, Simon Rosenberg, Véronique Nève, Rumyana Yankova, Barbara Ballmer-Weber, Maria Jose Goikoetxea, María José Barasona Villarejo, Teija Dunder, Tina Vesel, Elisa Gritti, Marianne van Hage, Laure Castan, Etienne Beaudouin, Margherita Di Costanzo, Natalia Ukleja-Sokołowska, Matthew Sperrin, Paul Turner, Saskia Albroscheit, Rebeca Lopez, Sonja Posega Devetak, Francisca Palomares, Laetitia Sellam, Jennifer Hammond, Astrid G. Kruizinga, Konrad Furmanczyk, Patricia Macchiaverni, Olga Pakholchuk, I V Vorozhko, Ania Carsin, Aleksandar Bulog, Joris Mens, Bianca Balbino, James P. Hindley, Jaap H. Akkerdaas, Jonathan Hourihane, Hilde Cnossen, Tatyana A Popova, Rupert Schlags, Natalia Nenasheva, A. Ehrenberg, Sigurveig T. Sigurdardottir, Anna Iliopoulou, Clara Ippolito, Piotr Samel-Kowalik, Paloma Campo, Gador Bogas, Constantinos Pitsios, Sarah Grosche, Karla Leversia Borjas Aguilar, Amena Warner, Birgit Kalb, Lénaïck Dupuis, Harry J. Wichers, Diana Silva, Gabriele Piuri, Linus Grabenhenrich, Emanuel Sarinho, M. Eleonore Pettersson, Rodrigo Barderas, Gary Stiefel, E. N. Clare Mills, Lali Saginadze, Ruta Dubakiene, Francesca Cipriani, Mindy Tsai, Marina Themisb, Michela Ciancamerla, Rebecca Knibb, Ruperto González-Pérez, Marina Peredelskaya, André C. Knulst, Irene Berends, S N Denisova, Montserrat Fernandez-Rivas, Paolo Maria Matricardi, Daniel Sampaio, Giorgio Bedogni, Sira Miquel, Koen Smit, Stefania Arasi, Sylvia Osscini, Justine Courtois, Cristina Deaconu, Srdan Banac, Kirsten Hansen, Jennette Higgs, Charlotte Hands Plovdiv, Carlotta Povesi Dascola, Noe Ontiveros, Rik Schrijvers, Carla Mastrorilli, Maria Passioti, Sebastian Tschirner, Bjorn R. Ludviksson, Joana Caiado, Daniel Corbacho, Sophie Nutten, Agustin Madroñero, Marina Suárez Vergara, Boudewjin J. Kollen, Catherine J Nock, Johanna Rost, Agnieszka Lipiec, Skadi Kull, Geert Houben, Carlo Caffarelli, Jordi Roca-Ferrer, Bolesław Samoliński, Isabelle Cleach, Colette Larré, Aideen Byrne, Corinne Herouet-Guicheney, Jonas Lidholm, Vera Assmann, W. Marty Blom, Adriano Mari, Adam T. Fox, Giuseppe Crisafulli, Afke M. M. Schins, Anastasia Papadopoulou, Flávio Sano, Richard Cooke, Franziska Ruëff, L Jorjoliani, Rebekah Sayers, Anne-Marie Kochuyt, Borja Bartalomé, Anne Moneret-Vautrin, Juan Carlos Julia, Jelena Mihailovic, Katarzyna Pyrz, Kollen Boudewijn, Margherita Varini, Paolo Giordani, Claudia Alessandri, Johanna van der Valk, Antoine Deschildre, Mariam Tskhakaia, Rosina López-Fandiño, Omar Kheroua, Nicolette J. T. Arends, Alina Zbróg, Chung-Hsiung Huang, Andrea Wangorsch, Ulf Bengtsson, Jim Langridge, Dasha Roa-Medellín, Jose Ignacio Larco, Bert Popping, Ana Prieto del Prado, José Antonio Bácter Martos, Rita Nocerino, Sophia Watts, Elisa Haroun, Danilo Villalta, Lee A. Gethings, María Ángeles Algaba Mármol, Ewa Gawrońska-Ukleja, Cornelia Jansen, André Moreira, V A Revyakina, Robert Zacniewski, Xavier Domingo Miró, Francesco Macrì, Mayra de Barros Dorna, Akanksha Sharma, Stephen J. Till, Ali Almontasheri, Chrystyna Kalicinsky, Robbert Sutorius, Akila Rekima, Mark A. Blankestijn, Nicolette Arends, Chiara Pistoletti, Merima Bublin, Manuel Pereira-Barbosa, Reyna Simon, Martin Karjalainen, Sam Mehr, Tushar Banerjee, Carmen Riggioni, Bertrand Evrard, Antonio Carlos Pastorino, Lidia Ilènko, Nikolaos Douladiris, Miguel Vieira, Erik Wambre, Francisco Cabrera-Chavez, Nikos G. Papadopoulos, Piotr Humeniuk, Gert van Duijn, Francesco Zinno, Young-Ae Lee, Lisa Tuppo, Hans de Groot, Léon M.J. Knippels, Pawel Dubiela, Henrik Fomsgaard Kjaer, Andrea Vereda, Djamel Saidi, Kok Loong Ue, Henk Van Loveren, Maria Jose Rodriguez, Marta Lomikovska, Elodie Michaud, Josefina Cernadas, Carmen Ponce, Marysia Recto, Frances Smith, Hassan Al-Dhekri, Shinobu Sakai, Thomas Eiwegger, Ana Rodolfo, Diego Peroni, Nikki Edelbroek, Waltraud Suer, Jenny van Odijk, Irena Nedelea, Borja Bartolomé, Lauren Lissner, Marjeta Sedmak, Annette Jamin, Italo De Vitis, Bo Pontoppidan, Annabelle Capt, Diego G. Peroni, Susana Rodrigues, Juan Carlos López-Rodríguez, David Endesfelder, Lesya Besh, Danila Zennaro, Charlotte G. Mortz, Kati Palosuo, María José Torres, Esozia Arroabarren, Lynne Regent, Laura Valdesoiro Navarrete, Ana Molina, Agha Rehan Khaliq, Phil Couch, Ana Miranda, Thomas Marichal, Riccardo Asero, Denise Borges, Dikla Pivko Levy, Miriam Palacios, Mireille Eb, Stephen J. Galli, Karin Hoffmann-Sommergruber, Anna Gudrun Vidarsdottir, Ifigenia Sfika, André Wolterbeek, Mauro Calvani, Edward F. Knol, Joyce A. M. Emons, Anne-Marie Oomkes-Pilon, Montserrat Bosque García, Daniel Lozano-Ojalvo, Filip Raciborski, Deirdre Galloway, Nanna Juel-Berg, Margareta Brandt Gertmo, Cornelia Bergmayr, Rob Klemans, Juliane Gregersen, Yolanda Meijer, Bettina Brix, Susanne Lau, Karine Adel-Patient, Hanneke van der Kleij, Mareike Price, Jean-Louis Mege, Lizalet Oosthuizen, Agurtzane Bilbao, Indre Butiene, Antonino Romano, Colin Barber, Rosana Camara Agondi, Nour Baïz, Soraya Ainad Tabet, Peter Korošec, Laurian Jongejan, Francine C. van Erp, José Pedro Moreira Silva, Nandinee Patel, Jaime Lozano, Prescilla V. Jeurink, Artur Walkiewicz, Bryan M. Harvey, Tiina J. Kauppila, Aida Semic-Jusufagic, Marianna Murdjeva, Miren Arteaga, Y. Bouferkas, Geunwoong Noh, Henny G. Otten, Sabine Dölle, Christopher Munro, O Dominguez, Gerard H. Koppelman, Leonieke N. van Veen, Vasti Iancu, Georg Mitterer, Patrizia Polverino de Laureto, Juliane Schulz, Ewa Ternesten Hasseus, Caroline Zimmermann, Ivona Barcievic-Jones, Shira Benor, Susanne Schwarz, Eun Ha Jang, Josefina Rodrigues Cernadas, Tadej Avcin, Joseph L. Baumert, Pernille Winther, Stéphane Leteurtre, Gabriela Canto, Louise J Michaelis, Jorge Alvarez, Gabriel Gastaminza, Michela Carola Speciani, Rute Gonçalves, Leire Dopazo, Evgen Benedik, Susanne C. Diesner, Luc S. De Clerck, A. Wesley Burks, Maurits S. van Maaren, Salvatore Tripodi, Philippe Aubert, Kamel Eddine El Mecherfi, Aline B. Sprikkelman, Ana Prieto, Margitta Worm, Edyta Krzych, Maja Krstic, Iride Dello Iacono, Melanie Cap, Alf Weimann, Maria Nassiri, Niels Röckendorf, Vladyslava Barzylovych, Marcia C. Mallozi, Pierre Bruhns, Jeanette Fisker Trandbohus, Ekaterini Papadopoulou, Vicente Albendiz, Timothy Watts, Uta Jappe, Javier Moreno, Maria Carmen Verga, Beatriz Secades Barbado, Carmen Di Scala, Roy Gerth van Wijk, Vladimir Mićović, Esther Barrionuevo, Giampaolo Ricci, Luisa Galindo, Ana Paula Beltran Moschione Castro, Oona Mustonen, Jia Yin, Lucia Caminiti, Jorge Esparza-Gordillo, N Adamia, Anna-Maija Hanni, Romy Gadisseur, Stefano Luccioli, Regina Treudler, Rosetta Ferrara, M. Guendouz, Jaakko Yrjänä, Philipp Starkl, Premendra D. Dwivedi, Javier Cuesta-Herranz, Johan Garssen, Ekaterini Goudouris, Sridevi Muralidharan, Kate Grimshaw, Carolina Sanchez Aranda, Ioana Maris, Manzoor Ahmed, Hajime Karasuyama, Stephanie Claus, Chantal Agabriel, Karen English, Dorien Van Ginkle, Eleonora Savi, Loredana Chini, Ine I. Decuyper, Sabine Schnadt, Valérie Trendelenburg, Jean-Luc Fauquert, Maurizio Mennini, Nikolaos Mikos, Ana Célia Costa, Steve L. Taylor, A. A. Schoemaker, Sara Abián, Margo M. Hagendorens, Andrea Di Rienzo Businco, Melina Makatsori, Eugénia Matos, Lucy Walker, Nikolaos A. Kitsioulis, David Alejandro Mendoza Hernández, Maria Starkhammar, Djordje Filipovic, Aine Adams, Mukul Das, Sonsoles Intente-Herrero, Natalia Blanca López, Marek L. Kowalski, Diana Deleanu, Bernard P. Mahon, Jean-Michel Wal, Lucia Decastelli, Mihaela Popescu, Aimee Lou Nano, Eva Batanero, Tong-Rong Jan, Yolanda Puente, Jacek Borowicz, Aimée Dorkenoo, J. Östling, Mashary Altamimi, Michel Neunlist, Zerrin Yalvaç, Sonia Ricò, Wentong Xue, Linda Cosenza, David C. A. Candy, Robert D. Voyksner, Montserrat De Prada, Abdulhadi Al-Qahtani, Sébastien Holvoet, Wolf-Meinhard Becker, Meropi D. Kontogianni, Bruno Pereira, F. Pineau, Eva Corbet, Kirsten Mehlig, Rosella De Poi, Jolanda H. M. van Bilsen, José Luís Plácido, Hans-Jørgen Malling, Chia-Chi Wang, Philip Couch, Kerrie Kirk, Agata Michalska, Sylke Rietz, Mariya Ivanovska, Victor Matheu-Delgado, Carl Hamsten, Francisca Gómez, Neusa Falbo Wandalsen, Mika J. Mäkelä, Tatyana Sentsova, Kristian Bravin, Philippe Delahaut, Hervé Bernard, Leonor Carneiro-Leão, Michele Miraglia del Giudice, Elena D. Kuvshinova, Jochen Behrends, Caroline Klingebiel, Meta Accetto, Claire Mills, Mariona Pascal, Miguel García Domínguez, Huan Rao, Carmen Saviana Ganea, Umberto Pelosi, Stefano Pattini, Bodo Niggemann, Annamaria Bianchi, Laura Martín-Pedraza, Anna Selby, Cristina Bueno, Stefan Vieths, Luis Felipe Ensina, Florin-Dan Popescu, Antonio Fernandez, Soren Wille, Erna Van Hoeyveld, Carina Kelleher, Athina L. Van Gasse, Anders Blom Jensen, Zorica Zivkovic, Moshe Ben-Shoshan, Sara Pereiro Fernández, Ronald van Ree, Antima Banerjee, Pablo Merida, Mandy Ziegert, Barbara Wróblewska, Morten Christensen, Gador Gomez, Pablo San Segundo-Acosta, Khaled Messaoudi, Anne-Sofie Ravn Ballegaard, Mikael Kuitunen, David Luyt, Vito Sabato, Nesrine Zaabat, Svitlana Zubchenko, Julien Labreuche, Elin Lustig, Katharina Blumchen, Guillaume Pouessel, Ana Fiandor, Stéphanie Lejeune, Paola Dignetti, Helen Brown, Anastasia Cirisano, Evangelia Kompoti, Anna Sokolova, Mercedes Escarrer Jaume, Shan Deng, Dirceu Solé, Chiara Fiamingo, Alessandro Travaglini, Nicolas Gaudenzio, Zbigniew Bartuzi, Antonia Rojas, Roberta Olcese, Nanju Alice Lee, Sandra Brandhoff, Lucien F. Harthoorn, Anna Maria Szyc, Andrea Costanzi, Sabine Pfeifer, Emiliano De Dominicis, Chiara Rafaiani, Yin-Hua Cheng, Elida Nikolla, Ignacio García Núñez, Diego Faggian, Lieve Coorevits, Ayelet Rimon, Erika Jensen-Jarolim, Jacqueline J.M. Castenmiller, Kristin Verbeke, Sean Bennett, Paraskevi Xepapadaki, Glauce Hiromi Yonamine, Anna Wawrzeńczyk, Rusudan Karseladze, Emmanouil Manousakis, Fiona Ward, Ivana Filipovic, Marie Bodinier, Viviana Moschese, Pedro Giavina Bianchi, Alice Coimbra, Alena Berger, Anton A. Shekhetov, Monica Maćków, Philippe Egenmann, Oscar Asensio, Lidia Hanna Markiewicz, Chun-Wei Tung, Zsolt Szépfalusi, Jan Knol, Frits Koning, Carolina S. Aranda, Annick Bastiaensen, Giovanni Battista Pajno, Leticia Pérez-Rodríguez, Ewout W. Steyerberg, Riccardo Sibilano, Valérie Verhasselt, Roberta Lupi, Lukasz Sokolowski, Adam Wawrzeńczyk, Dimitris I. Mitsias, Andreia Forno, Antoine Magnan, Christian Schwager, Ioanna Manolaraki, Alessandro Fiocchi, Tanja Rouhani Rankouhi, Carla Jones, Ana Pereira, Hannah M. Kansen, Michael Clausen, D. Bignardi, Assad M. Butt, Julie C. Locklear, Katrine Lindholm Bøgh, Valery Muhortnich, María Teresa Giner, Juan Miguel Garcia, Maria Luisa Somoza, Raditsa Sokolova, Maria Pasioti, Mirjana Zupancic, Joana Vitte, Duncan Brown, Arnaldo Porto, M. Turfkruyer, Lau Fabricius Larsen, Filipe Benito-Garcia, Mayra Coutinho Andrade, Meltem Ugras, Ingrid Sutic, Rand K. Arnaout, Etienne Cavalier, Marta Neto, Grégory Bouchaud, Elena Varin, Bushra Javed, Carla Camerotto, Monica Bronkowska, Cristiano Caruso, Luís Amaral, Jackeline F. Motta, Sahar Elshorbagi, Cornelis K. van der Ent, Alexandra Rodrigues, Silvia Peveri, Juan Heber Castellanos, Muriel Totis, Joan Bartra, Gjustina Loloci, Ivana Giangrieco, Ekaterina Khaleva, Joaquín Navarro, Kayoko Matsunaga, Jlenia Fresta, Jonathan O'b Hourihane, Sabina Bijlsma, Ana Rodriguez-Fernandez, Rosita Aitoro, Daniela Manila Bianchi, Rosa Jimenez-Feijoo, Mario Plebani, Marleen T. J. Van Ampting, Anthony E.J. Dubois, Clémence Mordacq, Simone Frediani, Martin Chapman, Helena Larramona, Fabrícia Carolino, Yanne Boloh, Ivona Baricevic-Jones, Mathilde Claude, Caroline Thumerelle, Päivi Vähäsarja, Mareen R. Datema, Abdullah Alfhaid, Diana Perez Alzate, Laura Santos-Diez, Graham King, Maria Teresa Guerra Perez, Jean-Marie Renaudin, Frieke Kuper, Josué Alejandro Huertas Guzmán, Harry Wichers, Thomas Keil, A. Haddi, Jennifer Santos, Regina Selb, Aida del Campo García, Maria Basagaña, Valentino Pavišić, Angela Simpson, Chris H. Bridts, Susana Piedade, Silvia Gallina, Isabella Pali-Schöll, Inês Pádua, Margaretha A. Faber, Frédéric de Blay, Luís Câmara Pestana, Ben Remington, Anna S. Pelkonen, Sandra Lucarelli, Ivana Šutić, Olivier Tranquet, Montserrat López Onieva, Antonio Amoroso, Paola Minale, Katia Basello, George Du Toit, Daniela Adriano, Adnan Custovic, Zbikowska-Gotz M, Domingo Barber, Inmaculada Doña, Christine Breynaert, Hanan Sharif, Manon M. Oude Nijhuis, Sandra Denery, Bertine M. J. Flokstra-de Blok, Rinkesh Kumar Gupta, Pieter-Jan de Kam, Dianne E. Campbell, Carmen M. D'Amelio, Nunzia Maiello, Ingo Marenholz, José María Ignacio García, Helen Lindqvist, Lilian Moraes, Cleonir Lui de Moraes Beck, Eunice Dias de Castro, Cono Casale, Barbara Majkowska-Wojciechowska, Maria Petrodimopoulou, Andrea Mikkelsen, Hub P. J. M. Noteborn, Hulya Ercan Saricoban, Moira Austin, Martinus Løvik, Graham Roberts, Isabella Annesi-Maesano, Aeilko H. Zwinderman, Sigrun H. Lund, Anouska D. Michelsen-Huisman, Fernando Bandrés Sánchez-Cruz, Francisco Javier Ruano, Valérie Liabeuf, Eman Madbouly, Pasquale Comberiati, Maria Isabel Garcimartin, Stephan Scheurer, Inna A. Larkova, Jean Tratt, Renata Rodrigues Cocco, Younes Belabbas, Lorella Paparo, Elizabeth Griffiths, Gian Lodovico Rapaccini, Audrey Dunn Galvin, Zizi Cojocariu, Isidor Hutteger, Claire Claverie, S.M. Nedelska, Anna Kuklinska-Pijanka, Jenny Badas, Mónica Piquer, Iztok Devetak, A.K.F. Gushken, Frans Timmermans, Adriana Machinena, Francisco Javier Monteseirin, Amaranta Traversa, Fátima Cabral Duarte, Tomaž Poredoš, Peter Meyer, Cristina Arêde, Rosa Muñoz-Cano, Barbara Pfitzner, Alejandro Joral, Juan Carlos Daza, Laurent L. Reber, Olga Chernyak, and Maria Antonetta Ciardiello

Subjects
Pulmonary and Respiratory Medicine, Allergy, medicine.medical_specialty, 030504 nursing, business.industry, Immunology, RC581-607, medicine.disease, Meeting Abstracts, 03 medical and health sciences, 0302 clinical medicine, Food allergy, 030225 pediatrics, Family medicine, medicine, Immunology and Allergy, Immunologic diseases. Allergy, 0305 other medical science, business, Anaphylaxis
Published
2017
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10. VA-086 methacrylate gelatine photopolymerizable hydrogels: A parametric study for highly biocompatible 3D cell embedding

Author

Paola Occhetta, Marco Rasponi, Laura Russo, Roberta Visone, Laura Cipolla, and Matteo Moretti

Subjects
food.ingredient, Materials science, Metals and Alloys, Biomedical Engineering, Methacrylate, Gelatin, Biomaterials, 3D cell culture, food, Photopolymer, Tissue engineering, Self-healing hydrogels, Ceramics and Composites, Photoinitiator, Prepolymer, Biomedical engineering
Abstract

The ability to replicate in vitro the native extracellular matrix (ECM) features and to control the three-dimensional (3D) cell organization plays a fundamental role in obtaining functional engineered bioconstructs. In tissue engineering (TE) applications, hydrogels have been successfully implied as biomatrices for 3D cell embedding, exhibiting high similarities to the natural ECM and holding easily tunable mechanical properties. In the present study, we characterized a promising photocrosslinking process to generate cell-laden methacrylate gelatin (GelMA) hydrogels in the presence of VA-086 photoinitiator using a ultraviolet LED source. We investigated the influence of prepolymer concentration and light irradiance on mechanical and biomimetic properties of resulting hydrogels. In details, the increasing of gelatin concentration resulted in enhanced rheological properties and shorter polymerization time. We then defined and validated a reliable photopolymerization protocol for cell embedding (1.5% VA-086, LED 2 mW/cm2) within GelMA hydrogels, which demonstrated to support bone marrow stromal cells viability when cultured up to 7 days. Moreover, we showed how different mechanical properties, derived from different crosslinking parameters, strongly influence cell behavior. In conclusion, this protocol can be considered a versatile tool to obtain biocompatible cell-laden hydrogels with properties easily adaptable for different TE applications.

Published
2014
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11. In vivoevaluation of bone deposition in macroporous titanium implants loaded with mesenchymal stem cells and strontium-enriched hydrogel

Author

Silvia Lopa, Camilla Recordati, Francesco Segatti, Giuseppe Talò, David Mercuri, Sara Previdi, Luigi Zagra, Matteo Moretti, and Arianna B. Lovati

Subjects
Biomaterials, Fluorescence-lifetime imaging microscopy, Decellularization, Materials science, In vivo, Mesenchymal stem cell, Biomedical Engineering, Histology, Implant, Progenitor cell, Osseointegration, Biomedical engineering
Abstract

Bone–implant integration represents a major requirement to grant implant stability and reduce the risk of implant loosening. This study investigates the effect of progenitor cells and strontium-enriched hydrogel on the osseointegration of titanium implants. To mimic implant–bone interaction, an ectopic model was developed grafting Trabecular Titanium™ (TT) implants into decellularized bone seeded with human bone marrow mesenchymal stem cells (hBMSCs). TT was loaded or not with strontium-enriched amidated carboxymethylcellulose (CMCA) hydrogel and/or hBMSCs. Constructs were implanted subcutaneously in athymic mice and osteodeposition was investigated with microcomputed tomography (micro-CT), scanning electron microscopy (SEM), and pull-out test at 4, 8, and 12 weeks. Fluorescence imaging was performed at 8 and 12 weeks, histology at 4 and 8 weeks. Micro-CT demonstrated the homogeneity of the engineered bone in all groups, supporting the reproducibility of the ectopic model. Fluorescence imaging, histology, SEM and pull-out mechanical testing showed superior tissue ingrowth in TT implants loaded with both strontium-enriched CMCA and hBMSCs. In our model, the synergic action of the bioactive hydrogel and hBMSCs increased both the bone deposition and TT integration. Thus, we suggest that using orthopedic prosthetic implant preloaded with strontium-enriched CMCA and seeded with BMSCs could represent a valid single-step surgical strategy to improve implant osseointegration. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 448–456, 2015.

Published
2014
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12. Generating Multicompartmental 3D Biological Constructs Interfaced through Sequential Injections in Microfluidic Devices

Author

Roberta Visone, Alberto Redaelli, Giovanni Stefano Ugolini, Marco Rasponi, and Matteo Moretti

Subjects
0301 basic medicine, Novel technique, Materials science, Microfluidics, Cell Culture Techniques, Biomedical Engineering, Pharmaceutical Science, Biocompatible Materials, Nanotechnology, 02 engineering and technology, Molding (process), Controlled studies, composite 3D constructs, Biomaterials, 03 medical and health sciences, chemistry.chemical_compound, Lab-On-A-Chip Devices, Microfluidic channel, Dimethylpolysiloxanes, biofabrication, microfluidics, microtissues, organs-on-chip, 3003, microtissues, Polydimethylsiloxane, Hydrogels, 021001 nanoscience & nanotechnology, organs-on-chip, 030104 developmental biology, chemistry, Self-healing hydrogels, 0210 nano-technology, Biofabrication, Biomedical engineering
Abstract

A novel technique is presented for molding and culturing composite 3D cellular constructs within microfluidic channels. The method is based on the use of removable molding polydimethylsiloxane (PDMS) inserts, which allow to selectively and incrementally generate composite 3D constructs featuring different cell types and/or biomaterials, with a high spatial control. The authors generate constructs made of either stacked hydrogels, with uniform horizontal interfaces, or flanked hydrogels with vertical interfaces. The authors also show how this technique can be employed to create custom-shaped endothelial barriers and monolayers directly interfaced with 3D cellular constructs. This method dramatically improves the significance of in vitro 3D biological models, enhancing mimicry and enabling for controlled studies of complex biological districts.

Published
2017
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13. Selective effects of a 4-oxystilbene derivative on wild and mutant neuronal chick α7 nicotinic receptor

Author

Matteo Moretti, Cecilia Gotti, Laura Maggi, Fabrizio Eusebi, Francesco Clementi, Eleonora Palma, and B. Balestra

Subjects
Pharmacology, Agonist, Methyllycaconitine, medicine.medical_specialty, medicine.drug_class, Biology, Receptor antagonist, Molecular biology, chemistry.chemical_compound, Nicotinic agonist, Ganglion type nicotinic receptor, Endocrinology, nervous system, chemistry, Internal medicine, Epibatidine, medicine, Alpha-4 beta-2 nicotinic receptor, Receptor, medicine.drug
Abstract

1. We assessed the pharmacological activity of triethyl-(beta-4-stilbenoxy-ethyl) ammonium (MG624), a drug that is active on neuronal nicotinic receptors (nicotinic AChR). Experiments on the major nicotinic AChR subtypes present in chick brain, showed that it inhibits the binding of [125I]-alphaBungarotoxin (alphaBgtx) to the alpha7 subtype, and that of [3H]-epibatidine (Epi) to the alpha4beta2 subtype, with Ki values of respectively 106 nM and 84 microM. 2. MG624 also inhibited ACh elicited currents (I(ACh)) in the oocyte-expressed alpha7 and alpha4beta2 chick subtypes with half-inhibitory concentrations (IC50) of respectively 109 nM and 3.2 microM. 3. When tested on muscle-type AChR, it inhibited [125I]-alphaBgtx binding with a Ki of 32 microM and ACh elicited currents (I(ACh)) in the oocyte-expressed alpha1beta1gammadelta chick subtype with an IC50 of 2.9 microM. 4. The interaction of MG624 with the alpha7 subtype was investigated using an alpha7 homomeric mutant receptor with a threonine-for-leucine 247 substitution (L247T alpha7). MG624 did not induce any current in oocytes expressing the wild type alpha7 receptor, but did induce large currents in the oocyte-expressed L247T alpha7 receptor. The MG624 elicited current (I(MG62)) has an EC50 of 0.2 nM and a Hill coefficient nH of 1.9, and is blocked by the nicotinic receptor antagonist methyllycaconitine (MLA). 5. These binding and electrophysiological studies show that MG624 is a potent antagonist of neuronal chick alpha7 nicotinic AChR, and becomes a competitive agonist following the mutation of the highly conserved leucine residue 247 located in the M2 channel domain.

Published
1999
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14. 4-Oxystilbene compounds are selective ligands for neuronal nicotinic α Bungarotoxin receptors

Author

Luigi Villa, Cecilia Gotti, Matteo Moretti, Giuseppe Rossoni, Francesco Clementi, B. Balestra, G.E. Rovati, Laura Maggi, Marco Pallavicini, and Ferruccio Berti

Subjects
Pharmacology, medicine.medical_specialty, Neurotransmission, Biology, Molecular biology, Nicotinic acetylcholine receptor, Endocrinology, Nicotinic agonist, Epibatidine, Internal medicine, medicine, Homomeric, Receptor, Acetylcholine, medicine.drug, Acetylcholine receptor
Abstract

1. Starting from the structure of an old 4-oxystilbene derivate with ganglioplegic activity (MG624), we synthesized two further derivates (F2 and F3) and two stereoisomers of F3 (F3A and F3B), and studied their selective effect on neuronal nicotinic acetylcholine receptor (AChR) subtypes. 2. MG 624, F3, F3A and F3B inhibited of 125I-alphaBungarotoxin (alphaBgtx) binding to neuronal chick optic lobe (COL) membranes, with nM affinity, but inhibited 125I-alphaBgtx binding to TE671 cell-expressed muscle-type AChR only at much higher concentrations. 3. We immobilized the alpha7, beta2 and beta4 containing chick neuronal nicotinic AChR subtypes using anti-subunit specific antibodies. MG 624, F3, F3A and F3B inhibited 125I-alphaBgtx binding to the alpha7-containing receptors with nM affinity, but inhibited 3H-Epi binding to beta2-containing receptors only at very high concentrations (more than 35 microM); their affinity for the beta4-containing receptors was ten times more than for the beta2-containing subtype. 4. Both MG624 and F3 compounds inhibited the ACh evoked currents in homomeric oocyte-expressed chick alpha7 receptors with an IC50 of respectively 94 and 119 nM. 5. High doses of both MG 624 and F3 depressed the contractile response to vagus nerve stimulation in guinea pig nerve-stomach preparations although at different IC50s (49.4 vs 166.2 microM) The effect of MG624 on rat nerve-hemidiaphragm preparations was 33 times less potent than that of F3 (IC50 486 vs 14.5 microM). 6. In conclusion, MG624 and F3 have a high degree of antagonist selectivity for neuronal nicotinic alphaBgtx receptors containing the alpha7 subunit.

Published
1998
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15. Detection of antibody classes and subpopulations in Myasthenia gravis patients using a new nonradioactive enzyme immunoassay

Author

Matteo Moretti, Francesco Clementi, Cecilia Gotti, Socrates J. Tzartos, B. Balestra, and Renato Mantegazza

Subjects
animal structures, Physiology, medicine.drug_class, Immunoprecipitation, Monoclonal antibody, Immunoglobulin G, Immunoenzyme Techniques, Epitopes, Cellular and Molecular Neuroscience, Physiology (medical), Myasthenia Gravis, medicine, Humans, Antibodies, Blocking, Autoantibodies, Acetylcholine receptor, biology, medicine.diagnostic_test, business.industry, Antibodies, Monoclonal, Bungarotoxins, Enzymes, Immobilized, medicine.disease, Precipitin Tests, Myasthenia gravis, Titer, Immunoglobulin M, Immunoassay, Immunology, Acetylcholinesterase, biology.protein, Polystyrenes, Binding Sites, Antibody, Neurology (clinical), Antibody, business
Abstract

To investigate the presence of antibodies in myasthenia gravis (MG) patients, we have developed a new reproducible and sensitive enzyme immunoassay (EIA-AChR), in which a β subunit-specific monoclonal antibody (mAb 73) immobilizes fetal calf acetylcholine receptors (AChRs). We tested 92 MG patients (42 with positive and 50 with negative antibody titers), 60 healthy controls, and 40 controls with other autoimmune diseases. EIA-AChR detected immunoglobulin G (IgG) titers in all of the seropositive samples, with a significant correlation between these and those obtained using the traditional immunoprecipitation method. Moreover, 5 seronegative patients at immunoprecipitation assay were positive at EIA-AChR. EIA-AChR was also useful in revealing: (1) a seropositive patient subpopulation with generalized MG who had Abs directed against α-Bungarotoxin binding sites; and (2) patients with IgM directed against fetal calf AChR (detected in 13 seronegative and 16 seropositive MG patients, and in 6 of the patients with other autoimmune diseases). © 1997 John Wiley & Sons, Inc. Muscle Nerve20: 800–808, 1997

Published
1997
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16. Pharmacology and Biophysical Properties of α7 and α7 - α8 α-Bungarotoxin Receptor Subtypes Immunopurified from the Chick Optic Lobe

Author

M. Ballivet, Daniel Bertrand, Wolfgang Hanke, K. Maury, Matteo Moretti, Francesco Clementi, and Cecilia Gotti

Subjects
Agonist, biology, medicine.drug_class, General Neuroscience, Protein subunit, Xenopus, Alpha (ethology), Bungarotoxin, biology.organism_classification, Molecular biology, Biochemistry, Polyclonal antibodies, biology.protein, medicine, Homomeric, Receptor
Abstract

Two chick optic lobe alpha-bungarotoxin receptor subtypes (alpha 7 and alpha 7-alpha 8) were immunopurified using polyclonal antibodies raised against synthetic peptides of chick alpha 7 and alpha 8 alpha-bungarotoxin receptor subunits. The alpha 7 subtype contained the M(r) 57,000 alpha 7 subunit, and represented 60-70% of the alpha-bungarotoxin receptors; the alpha 7-alpha 8 subtype contained the M(r) 57,000 alpha 7 and alpha 8 subunits, and represented only 20-25% of the receptors. Both subtypes also had an additional M(r) 52,000 subunit. The affinity of these subtypes for alpha-bungarotoxin as well as antagonists was similar. However, the alpha 7-alpha 8 subtype displayed consistently higher affinities for agonists. When reconstituted in planar lipid bilayers, the alpha 7-alpha 8 subtype displayed several conductance states of 10-50 pS; the alpha 7 subtype had only one conductance state of 45 pS. The alpha 7-alpha 8 subtype was activated by lower agonist concentrations than the alpha 7 subtype. When expressed in Xenopus oocytes, the alpha 8 subunit formed functional homomeric receptors that desensitized rapidly. These channels were blocked by alpha-bungarotoxin and displayed a higher affinity for agonists than the alpha 7 homomeric receptor. Taken together, these data indicate that at least two alpha-bungarotoxin subtypes are present in the chick optic lobe. They operate as ligand-gated channels and display different agonist sensitivities and kinetics/conductance properties.

Published
1994
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