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Cannabidiol negatively modulates adenosine A2A receptor functioning in living cells
- Nuria Sánchez-Fernández, Laura Gómez-Acero, Laura I. Sarasola, Josep Argerich, Andy Chevigné, Kenneth A. Jacobson, Francisco Ciruela, Víctor Fernández-Dueñas, Ester Aso
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- Journal:
- Acta Neuropsychiatrica , First View
- Published online by Cambridge University Press:
- 22 August 2023, pp. 1-5
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Objectives:
Cannabidiol (CBD) is a phytocannabinoid with great potential in clinical applications. The mechanism(s) of action of CBD require further investigation. Previous studies suggested that adenosine A2A receptors (A2ARs) could play a role in CBD-induced effects. Here, we evaluated the ability of CBD to modify the function of A2AR.
Methods:We used HEK-293T cells transfected with the cDNA encoding the human A2AR and Gαs protein, both modified to perform bioluminescence-based assays. We first assessed the effect of CBD on A2AR ligand binding using an A2AR NanoLuciferase sensor. Next, we evaluated whether CBD modified A2AR coupling to mini-Gαs proteins using the NanoBiT™ assay. Finally, we further assessed CBD effects on A2AR intrinsic activity by recording agonist-induced cAMP accumulation.
Results:CBD did not bind orthosterically to A2AR but reduced the coupling of A2AR to Gαs protein and the subsequent generation of cAMP.
Conclusion:CBD negatively modulates A2AR functioning.
4423 Impact of Gender on High On-Treatment Platelet Reactivity (HPR) and Major Adverse Cardiovascular Events (MACEs) in Caribbean Hispanic patients using Clopidogrel
- Hector Jose Nunez Medina, Jorge Duconge, Luis A. Velez, Laura I. Fernandez, Orlando Arce
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, pp. 109-110
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OBJECTIVES/GOALS: The use of P2Y12 receptor inhibitors like Clopidogrel is crucial in the prevention of thrombotic events in patients with coronary artery disease, peripheral arterial disease, and cerebrovascular disease. Variation in the level of platelet inhibition is present in many patients, and it is associated with the occurrence of major adverse cardiovascular events (MACEs). The term High-on treatment platelet reactivity (HTRP) is used to describe impaired antiplatelet inhibition while on Clopidogrel. Multiple factors have been associated with the presence of HTPR in patients with CAD and PAD, including CYP2C19 loss of function polymorphism, drug-drug interactions, and medical comorbidities. Gender differences are another factor that might influence the levels of platelet inhibition while on Clopidogrel and hence, HTPR. Differences by Gender exist in platelet biology, count, and activation. The evidence for the influence of Gender in HTPR is limited, but a possible association has been described. In this study, we described the association of Gender with HTPR and Major Adverse Cardiovascular Events (MACEs) occurrence. The data is from a sample of Hispano-Caribbean patients on Clopidogrel therapy alone or in combination with Aspirin that were retrospectively evaluated from an ongoing trial in Puerto Rico. The result of this study provided evidence of the influence that Gender has on antiplatelet therapy function and MACEs occurrence. METHODS/STUDY POPULATION: The population in the study consisted of Hispano-Caribbean patients using Clopidogrel alone or in combination with Aspirin for coronary artery disease, peripheral arterial disease, or cerebrovascular disease. The sample was obtained from multiple hospital institutions with cardiovascular services in Puerto Rico during the years 2016-2019. Patients were part of the ongoing trial, “Adopting a precision medicine paradigm in Puerto Rico: leveraging ancestral diversity to identify predictors of Clopidogrel response in Caribbean Hispanics.” The sample size consisted of 150 patients. Participants were recruited during routine medical care, pre-admission evaluation for elective cardiac procedures, or during hospitalization in the participating institutions. Platelet reactivity testing was performed with the system Verify Now® to determine PRU values, and High on-treatment platelet reactivity was defined as PRU ≥208. One year after recruitment, the patients were re-evaluated for the occurrence of MACEs. The association of the variables HTPR, occurrence of MACEs, and Gender were assessed using logistic regression in addition to the role of HTPR and Gender for predicting MACE occurrence. The analysis was done using the statistic software Intellectus ©. RESULTS/ANTICIPATED RESULTS: The sample consisted of 67 females and 83 males with and Mean age of 67.87 years and 61.11 years, respectively. The prevalence of HTPR in the sample was 32.67 % (n = 49) with 36% (n = 24) for females, and 30%(n = 25) for males. The mean PRU values were 179.54 for females and 170.81 for males. The percentage of MACEs one year after recruitment was 29.33 % (n = 44) with 43% on females (n = 19), and 57% on males (n = 25). Logistic regression for Gender predicting HTPR was non-significant with a χ2(2) = 0.55, p = .758, and McFadden R2 = 0.00. Also, logistic regression for the effects of Gender and HTPR on the Odds of MACEs occurrence was not significant based on a model with an alpha of 0.05, χ2(2) = 1.99, p = .370, and McFadden R2 = 0.01. DISCUSSION/SIGNIFICANCE OF IMPACT: The sample consisted of 67 females and 83 males with and Mean age of 67.87 years and 61.11 years, respectively. The prevalence of HTPR in the sample was 32.67 % (n = 49) with 36% (n = 24) for females, and 30%(n = 25) for males. The mean PRU values were 179.54 (±70.42) for females and 170.81(±64.89) for males. The percentage of MACEs one year after recruitment was 29.33 % (n = 44) with 43% on females (n = 19), and 57% on males (n = 25). Logistic regression for Gender predicting HTPR was non-significant with a χ2(2) = 0.55, p = .758, and McFadden R2 = 0.00. Also, logistic regression for the effects of Gender and HTPR on the odds of MACEs occurrence was not significant based on a model with an alpha of 0.05, χ2(2) = 1.99, p = .370, and McFadden R2 = 0.01.
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- By Dag Aarsland, Angelo Antonini, Liana G. Apostolova, Marek Balaz, Roger A. Barker, Oscar Bernal-Pacheco, Mona K. Beyer, Başar Bilgiç, Daniel J. Burdick, Jessica Calleo, K. Ray Chaudhuri, Jeffrey Cummings, Turi O. Dalaker, Christine Daniels, Kathy Dujardin, Sheila R. Eichenseer, Murat Emre, Hubert H. Fernandez, Adam Gerstenecker, Christopher G. Goetz, Haşmet A. Hanağası, Kristina Røkenes Karlsen, Jaime Kulisevsky, Albert F. G. Leentjens, James B. Leverenz, Irene Litvan, Elisabet Londos, Laura Marsh, Saül Martínez-Horta, Pablo Martinez-Martin, Benjamin T. Mast, Brit Mollenhauer, Pouya Movahed, Agneta Nordberg, Javier Pagonabarraga, Irena Rektorova, Per Svenningsson, Alexander I. Tröster, Carolina Villa-Bonomo, Jens Volkmann, Ryan R. Walsh, Daniel Weintraub, Caroline H. Williams-Gray, Henrik Zetterberg
- Edited by Dag Aarsland, Jeffrey Cummings, Daniel Weintraub, University of Pennsylvania, K. Ray Chaudhuri
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- Book:
- Neuropsychiatric and Cognitive Changes in Parkinson's Disease and Related Movement Disorders
- Published online:
- 05 August 2013
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- 29 August 2013, pp vii-x
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- By Maricela Alarcón, Laura A. Baker, Trygve Bakken, Serena Bezdjian, Andrew W. Bergen, Laura J. Bierut, Andrew C. Chen, C. Robert Cloninger, David W. Craig, Anibal Cravchik, Raymond R. Crowe, Carlos Cruchaga, Joseph F. Cubells, Marcella Devoto, Stephen H. Dinwiddie, Howard J. Edenberg, Josephine Elia, Craig A. Erickson, Thomas V. Fernandez, Xiaowu Gai, Elliot Gershon, Daniel H. Geschwind, Alison M. Goate, Hugh M. D. Gurling, Hakon Hakonarson, Sarah M. Hartz, Akiko Hayashi-Takagi, Jinger Hoop, Hanna Jaaro-Peled, Atsushi Kamiya, John S. K. Kauwe, Walter H. Kaye, John R. Kelsoe, Karestan C. Koenen, Mary Jeanne Kreek, Francesca Lantieri, James F. Leckman, Ondrej Libiger, Falk W. Lohoff, Michael J. Lyons, Christopher J. McDougle, Andrew McQuillin, Kathleen Ries Merikangas, Maria G. Motlagh, Pablo R. Moya, Dennis L. Murphy, Eric J. Nestler, Alexander B. Niculescu, David A. Nielsen, Khendra I. Peay, Bernice Porjesz, James B. Potash, R. Arlen Price, Dmitri Proudnikov, Adrian Raine, Madhavi Rangaswamy, William Renthal, Akira Sawa, Nicholas J. Schork, Saurav Seshadri, Shelley D. Smith, Wanli W. Smith, Toshinobu Takeda, Ardesheer Talati, Yi-Lang Tang, Kiara Timpano, Ali Torkamani, Catherine Tuvblad, Myrna M. Weissman, Jens R. Wendland, Jennifer Wessel, Peter S. White, Vadim Yuferov, Tyler Zink
- Edited by John I. Nurnberger, Jr, Wade Berrettini, University of Pennsylvania School of Medicine
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- Book:
- Principles of Psychiatric Genetics
- Published online:
- 05 October 2012
- Print publication:
- 13 September 2012, pp vii-x
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- By Jane E. Adcock, Yahya Aghakhani, A. Anand, Eva Andermann, Frederick Andermann, Alexis Arzimanoglou, Sandrine Aubert, Nadia Bahi-Buisson, Carman Barba, Agatino Battaglia, Geneviève Bernard, Nadir E. Bharucha, Laurence A. Bindoff, William Bingaman, Francesca Bisulli, Thomas P. Bleck, Stewart G. Boyd, Andreas Brunklaus, Harry Bulstrode, Jorge G. Burneo, Laura Canafoglia, Laura Cantonetti, Roberto H. Caraballo, Fernando Cendes, Kevin E. Chapman, Patrick Chauvel, Richard F. M. Chin, H. T. Chong, Fahmida A. Chowdhury, Catherine J. Chu-Shore, Rolando Cimaz, Andrew J. Cole, Bernard Dan, Geoffrey Dean, Alessio De Ciantis, Fernando De Paolis, Rolando F. Del Maestro, Irissa M. Devine, Carlo Di Bonaventura, Concezio Di Rocco, Henry B. Dinsdale, Maria Alice Donati, François Dubeau, Michael Duchowny, Olivier Dulac, Monika Eisermann, Brent Elliott, Bernt A. Engelsen, Kevin Farrell, Natalio Fejerman, Rosalie E. Ferner, Silvana Franceschetti, Robert Friedlander, Antonio Gambardella, Hector H. Garcia, Serena Gasperini, Lorenzo Genitori, Gioia Gioi, Flavio Giordano, Leif Gjerstad, Daniel G. Glaze, Howard P. Goodkin, Sidney M. Gospe, Andrea Grassi, William P. Gray, Renzo Guerrini, Marie-Christine Guiot, William Harkness, Andrew G. Herzog, Linda Huh, Margaret J. Jackson, Thomas S. Jacques, Anna C. Jansen, Sigmund Jenssen, Michael R. Johnson, Dorothy Jones-Davis, Reetta Kälviäinen, Peter W. Kaplan, John F. Kerrigan, Autumn Marie Klein, Matthias Koepp, Edwin H. Kolodny, Kandan Kulandaivel, Ruben I. Kuzniecky, Ahmed Lary, Yolanda Lau, Anna-Elina Lehesjoki, Maria K. Lehtinen, Holger Lerche, Michael P. T. Lunn, Snezana Maljevic, Mark R. Manford, Carla Marini, Bindu Menon, Giulia Milioli, Eli M. Mizrahi, Manish Modi, Márcia Elisabete Morita, Manuel Murie-Fernandez, Vivek Nambiar, Lina Nashef, Vincent Navarro, Aidan Neligan, Ruth E. Nemire, Charles R. J. C. Newton, John O'Donavan, Hirokazu Oguni, Teiichi Onuma, Andre Palmini, Eleni Panagiotakaki, Pasquale Parisi, Elena Parrini, Liborio Parrino, Ignacio Pascual-Castroviejo, M. Scott Perry, Perrine Plouin, Charles E. Polkey, Suresh S. Pujar, Karthik Rajasekaran, R. Eugene Ramsey, Rahul Rathakrishnan, Roberta H. Raven, Guy M. Rémillard, David Rosenblatt, M. Elizabeth Ross, Abdulrahman Sabbagh, P. Satishchandra, Swati Sathe, Ingrid E. Scheffer, Philip A. Schwartzkroin, Rod C. Scott, Frédéric Sedel, Michelle J. Shapiro, Elliott H. Sherr, Michael Shevell, Simon D. Shorvon, Adrian M. Siegel, Gagandeep Singh, S. Sinha, Barbara Spacca, Waney Squier, Carl E. Stafstrom, Bernhard J. Steinhoff, Andrea Taddio, Gianpiero Tamburrini, C. T. Tan, Raymond Y. L. Tan, Erik Taubøll, Robert W. Teasell, Mario Giovanni Terzano, Federica Teutonico, Suzanne A. Tharin, Elizabeth A. Thiele, Pierre Thomas, Paolo Tinuper, Dorothée Kasteleijn-Nolst Trenité, Sumeet Vadera, Pierangelo Veggiotti, Jean-Pierre Vignal, J. M. Walshe, Elizabeth J. Waterhouse, David Watkins, Ruth E. Williams, Yue-Hua Zhang, Benjamin Zifkin, Sameer M. Zuberi
- Edited by Simon D. Shorvon, Frederick Andermann, Renzo Guerrini
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- The Causes of Epilepsy
- Published online:
- 05 March 2012
- Print publication:
- 14 April 2011, pp ix-xvi
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