Article
Pharmacology & Pharmacy
Simona De Gregori, Annalisa De Silvestri, Barbara Cattadori, Andrea Rapagnani, Riccardo Albertini, Elisa Novello, Monica Concardi, Eloisa Arbustini, Carlo Pellegrini
Summary: Tacrolimus is an immunosuppressant drug used for preventing organ rejection after transplantation. This study suggests that the concentration of tacrolimus in endomyocardial biopsies may be more relevant to the occurrence of acute rejection than the concentration in whole blood. Preliminary results indicate a possible association between low tacrolimus concentrations in endomyocardial biopsies and episodes of acute rejection.
Article
Biochemical Research Methods
Nynke Wijbenga, Marjolein M. Muller, Rogier A. S. Hoek, Bas J. Mathot, Leonard Seghers, Joachim G. J. Aerts, Brenda C. M. de Winter, Daniel Bos, Olivier C. Manintveld, Merel E. Hellemons
Summary: Close monitoring of immunosuppressant levels is essential for preventing complications after lung transplantation. The use of electronic nose technology as a non-invasive alternative for therapeutic drug monitoring shows weak correlation and inaccurate diagnostic and categorization capacity.
JOURNAL OF BREATH RESEARCH
(2023)
Article
Emergency Medicine
Emma L. Chee-How, Nicole M. Acquisto, Y. Victoria Zhang
Summary: The study evaluated the appropriateness of serum sample timing for tacrolimus measurement in the emergency department, finding that many initial TAC measurements were collected inappropriately, resulting in the need for additional measurements within 24 hours and increased unnecessary healthcare costs.
AMERICAN JOURNAL OF EMERGENCY MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Suwasin Udomkarnjananun, Thanee Eiamsitrakoon, Brenda C. M. de Winter, Teun van Gelder, Dennis A. Hesselink
Summary: The measurement of whole blood concentration of tacrolimus has been the primary method for therapeutic drug monitoring, but the pharmacologically active fractions are only a small fraction of the measured concentration. Measuring the intracellular tacrolimus concentration may better reflect its pharmacodynamic effects, but conflicting results have been reported. Improvement of the measurement technique and clinical evaluation are needed before its use in clinical practice.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Huaijun Zhu, Min Wang, Xiaofu Xiong, Yao Du, Danying Li, Zhou Wang, Weihong Ge, Yizhun Zhu
Summary: Inter- and intrapatient variability of tacrolimus exposure is a vital prognostic risk factor for the clinical outcome of liver transplantation. This study aimed to identify potential plasma metabolites associated with the dose-adjusted trough concentration of tacrolimus in liver transplant recipients using a global metabolomic approach. The results showed that microbiota-derived uremic retention solutes, bile acids, steroid hormones, and medium- and long-chain acylcarnitines were the main metabolites associated with the dose-adjusted trough concentration of tacrolimus.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Yuan Liu, Rui Wang, Peizhen Wen, Wenbin An, Jinxin Zheng, Tao Zhang, Pengshan Zhang, Haoyu Wang, Fan Zou, Hui Pan, Junwei Fan, Zhihai Peng
Summary: This study investigated the genetic risk of patients with tacrolimus intolerance after liver transplantation. The results suggested that switching to cyclosporine (SFTC) may increase the risk of dyslipidemia and insulin resistance, while specific SNPs of CYP3A5 gene could be potential genetic risks for tacrolimus intolerance.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Gwendal Coste, Florian Lemaitre
Summary: This review summarizes the evidence on the intra-patient pharmacokinetic variability (IPV) of tacrolimus concentrations in solid organ transplant recipients other than kidney transplantation. It discusses factors influencing IPV, the potential use of IPV as a biomarker for graft outcomes, and strategies to reduce IPV.
Article
Computer Science, Information Systems
Stuart J. Nelson, Allen Flynn, Mark S. Tuttle
Summary: The study aimed to develop an ontology for formalizing drug indications in a computable and comparable manner. A model was created to represent FDA-approved indications as disjuncts of conjuncts of assertions, with logical primitives chosen from 2 categories. The model successfully represented over 99% of approved treatment or prevention label indications, with challenges remaining in workflow design and terminology integration.
JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
(2021)
Article
Surgery
Bastian N. Ruijter, Maarten E. Tushuizen, Dirk J. A. R. Moes, Babs M. de Klerk, Bart van Hoek
Summary: This study evaluated the monitoring method of tacrolimus in stable liver transplant recipients, and found that 4-hour monitoring was not superior to trough monitoring in terms of its effect on renal function, but it was safe to use in an afternoon outpatient clinic.
CLINICAL TRANSPLANTATION
(2022)
Article
Pharmacology & Pharmacy
Natalia Riva, Manuel Ibarra, Zinnia P. Parra-Guillen, Maria Eugenia Galvan, Erika Perez, Guido Trezeguet Renatti, Paulo Caceres Guido, Clarisa Lopez, Nieves Licciardone, Esteban Halac, Marcelo Dip, Alejandro Cruz, Oscar Imventarza, Daniel Buamscha, Inaki F. Troconiz, Paula Schaiquevich
Summary: A population pharmacokinetic model of sublingually administered tacrolimus was developed in paediatric liver transplant patients who cannot swallow capsules. The disposition of tacrolimus was best characterized by a 2-compartment model, with clearance achieving half of the maximum elimination capacity at 4.6 days post-transplantation. Non-sedated patients had an increased first-order absorption rate constant and reduced bioavailability compared to sedated patients.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Environmental Sciences
Stavros Stagakis, Christian Feigenwinter, Roland Vogt, Markus Kalberer
Summary: This study develops a high-resolution bottom-up model that provides hourly maps of urban surface CO2 fluxes, including contributions from buildings, traffic, human respiration, soil respiration, plant respiration, and plant photosynthetic uptake. The model is designed to be simple and flexible, using commonly available data as input, making it transferable to different locations. Applied to Basel, Switzerland, the model captures the dynamic spatiotemporal variability of urban CO2 fluxes and estimates lower emissions from buildings and traffic compared to the local inventory.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Medicine, General & Internal
Tomasz Urbanowicz, Anna Olasinska-Wisniewska, Michal Michalak, Michal Rodzki, Anna Witkowska, Ewa Straburzynska-Migaj, Bartlomiej Perek, Marek Jemielity
Summary: There is a significant correlation between blood cell ratio and tacrolimus overdose, and an NLR above 3.62 may be regarded as a simple indicator of tacrolimus overdose.
Article
Pharmacology & Pharmacy
Binbin Lv, Longshan Liu, Xiaoman Liu, Min Huang, Xiao Chen, Kejing Tang, Changxi Wang, Pan Chen
Summary: In this study, the occurrence of tacrolimus-induced liver injury (tac-DILI) in renal transplant recipients was investigated. The most common type of tac-DILI was found to be the cholestatic pattern. Baseline ALP level, age, and body weight were identified as independent risk factors.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Xiang-Qian Gu, Dan Tang, Ping Wan, Tian Qin, Tai-Hua Yang, Ji Wu, Hao Ji, Jin-Chuan Liu, Feng Xue, Yuan-Jia Tang, Qiang Xia
Summary: The study shows that CYP3A5 gene polymorphism is the major factor influencing tacrolimus pharmacokinetics. Four miRNAs, including miR-29a-3p, miR-99a-5p, miR-532-5p, and miR-26b-5p, are identified as novel regulators of tacrolimus metabolism by affecting CYP3A5 expression through various mechanisms.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Yilei Yang, Xin Huang, Yinping Shi, Rui Yang, Haiyan Shi, Xinmei Yang, Guoxiang Hao, Yi Zheng, Jianning Wang, Lequn Su, Yan Li, Wei Zhao
Summary: A CYP3A5 genotype-dependent drug-drug interaction was found between tacrolimus and nifedipine in Chinese renal transplant patients. Personalized therapy accounting for CYP3A5 genotype detection and therapeutic drug monitoring is necessary for these patients receiving tacrolimus and nifedipine treatment.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Psychology, Clinical
E. Loeb, K. El Asmar, S. Trabado, F. Gressier, R. Colle, A. Rigal, S. Martin, C. Verstuyft, B. Feve, P. Chanson, L. Becquemont, E. Corruble
Summary: This study found that depressed patients have decreased NOS activity compared to healthy controls, and it improves after antidepressant treatment. NOS activity may be a promising biomarker for major depressive episodes in the context of major depressive disorder.
PSYCHOLOGICAL MEDICINE
(2022)
Article
Psychology, Clinical
Romain Colle, Khalil El Asmar, Celine Verstuyft, Pierre-Marie Lledo, Francoise Lazarini, Kenneth Chappell, Eric Deflesselle, Abd El Kader Ait Tayeb, Bruno Falissard, Emmanuelle Duron, Samuel Rotenberg, Jean-Francois Costemale-Lacoste, Denis J. David, Florence Gressier, Alain M. Gardier, Thomas Hummel, Laurent Becquemont, Emmanuelle Corruble
Summary: The study found significant differences in olfactory performance between depressed patients and healthy controls, but after venlafaxine treatment, some patients showed improvements in olfaction, which were mediated by the alleviation of depressive symptoms.
PSYCHOLOGICAL MEDICINE
(2022)
Article
Medical Laboratory Technology
Kenneth Chappell, Bruno Francou, Christophe Habib, Thomas Huby, Marco Leoni, Aurelien Cottin, Florian Nadal, Eric Adnet, Eric Paoli, Christophe Oliveira, Celine Verstuyft, Anne Davit-Spraul, Pauline Gaignard, Elise Lebigot, Jean-Charles Duclos-Vallee, Jacques Young, Peter Kamenicky, David Adams, Andoni Echaniz-Laguna, Emmanuel Gonzales, Claire Bouvattier, Agnes Linglart, Veronique Picard, Emilie Bergoin, Emmanuel Jacquemin, Anne Guiochon-Mantel, Alexis Proust, Jerome Bouligand
Summary: This study reports 5 years of experience in using the Galaxy platform for high-throughput sequencing data analysis in a clinical laboratory setting. The results demonstrate that Galaxy is a suitable platform with great potential to benefit patient care in a clinical laboratory setting.
CLINICAL CHEMISTRY
(2022)
Article
Clinical Neurology
Vianney Poinsignon, Romain Colle, Khalil El Asmar, Indira Mendez-David, Denis J. David, Abd El Kader Ait Tayeb, Kenneth Chappell, Florence Gressier, Hugo Herrero, Bruno Feve, Laurent Becquemont, Emmanuelle Corruble, Celine Verstuyft
Summary: The study assessed the association between the HTR4 genetic polymorphism rs1345697 and improvement in depressive symptoms and remission after antidepressant treatment in MDE patients. Results indicated that GG homozygous patients had lower improvements in depressive symptoms and 2-fold lower remission rates compared to allele A carriers.
JOURNAL OF AFFECTIVE DISORDERS
(2022)
Article
Psychology, Clinical
Abd El Kader Ait Tayeb, Romain Colle, Khalil El-Asmar, Kenneth Chappell, Cecile Acquaviva-Bourdain, Denis J. David, Severine Trabado, Philippe Chanson, Bruno Feve, Laurent Becquemont, Celine Verstuyft, Emmanuelle Corruble
Summary: This study found that patients with major depressive episodes have lower levels of peripheral acetyl-l-carnitine (ALC) and higher levels of l-carnitine compared to healthy controls. After antidepressant treatment, these imbalances are restored, and the severity of mitochondrial dysfunction may predict the response to treatment.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Rheumatology
France X. Mariette, O. Hermine, P-L Tharaux, M. Resche-Rigon, R. Porcher, P. Ravaud
Summary: Treatment with sarilumab did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival.
LANCET RHEUMATOLOGY
(2022)
Article
Genetics & Heredity
Simon Verdez, Quentin Thomas, Philippine Garret, Celine Verstuyft, Emilie Tisserant, Antonio Vitobello, Frederic Tran Mau-Them, Christophe Philippe, Marc Bardou, Maxime Luu, Abderrahmane Bourredjem, Patrick Callier, Christel Thauvin-Robinet, Nicolas Picard, Laurence Faivre, Yannis Duffourd
Summary: In addition to identifying causal genetic variants in the diagnosis of Mendelian disorders, exome sequencing can detect numerous variants relevant to clinical care. This information can be used to improve future health outcomes for patients and their at-risk relatives, such as preventing late-onset genetic disorders and identifying differential drug efficacy and safety.
PHARMACOGENOMICS JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Benjamin Portal, Flora Vasile, Jonathan Zapata, Camille Lejards, Abd El Kader Ait Tayeb, Romain Colle, Celine Verstuyft, Emmanuelle Corruble, Nathalie Rouach, Bruno P. Guiard
Summary: Studies suggest that astrocytic connexins (Cx) play an important role in regulating high brain functions and may be involved in psychiatric disorders and the therapeutic activity of antidepressant drugs. This study found that Cx inactivation affects the efficacy of antidepressant drugs in a mouse model of depression, and the combination of VENLA and CBX increases the risk of relapse.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Kenneth Chappell, Abd El Kader Ait Tayeb, Romain Colle, Jerome Bouligand, Khalil El-Asmar, Florence Gressier, Severine Trabado, Denis Joseph David, Bruno Feve, Laurent Becquemont, Emmanuelle Corruble, Celine Verstuyft
Summary: This study found that genetic variants of ARRB1 may influence the response to antidepressant drug treatment in depressed patients. The analysis of rare variants showed significant associations with changes in HDRS scores and remission. The results suggest that beta-arrestin 1 and genetic variants of ARRB1 may serve as useful clinical biomarkers for clinical improvement following antidepressant drug treatment in depressed individuals.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Solene Marie, Louise Breuil, Zacharias Chalampalakis, Laurent Becquemont, Celine Verstuyft, Anne-Lise Lecoq, Fabien Caille, Philippe Gervais, Vincent Lebon, Claude Comtat, Michel Bottlaender, Nicolas Tournier
Summary: Organic Anion-Transporting Polypeptides (OATPs) play an important role in controlling the liver uptake of drugs. However, the functional importance of OATPs in whole-body pharmacokinetics (WBPK) is not well understood. This study used dynamic whole-body positron emission tomography (DWB-PET) to investigate the impact of OATPs on liver uptake and WBPK of glyburide. The results showed that inhibition of OATPs led to decreased liver uptake of glyburide, but had negligible effect on its tissue distribution in nonhepatic organs.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Kenneth Chappell, Romain Colle, Jerome Bouligand, Severine Trabado, Bruno Feve, Laurent Becquemont, Emmanuelle Corruble, Celine Verstuyft
Summary: Genetic variants in the MAOA and MAOB genes are associated with clinical improvement and plasma 5HIAA/5HT ratio in patients treated with antidepressant drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Julie Bertrand, Aurelie Barrail-Tran, Lucie Fayette, Rada Savic, Cecile Goujard, Elina Teicher, Caroline Barau, Alain Pruvost, Anne-Marie Taburet, France Mentre, Celine Verstuyft, A. Barrail-Tran, A. Brunet, M. -J. Commoy, S. Couffin-Cadiergues, D. Descamps, X. Duval, C. Goujard, C. Le Guellec, F. Mentre, G. Nembot, A. -M. Taburet, B. Vrijens, G. Nembot, G. Unal, F. Mentre, X. Panhard, R. Savic, B. Vrijens
Summary: A model was established to predict the plasma concentrations of Tenofovir and emtricitabine, and it was found that the clearance of these drugs decreases with age, but is not significantly associated with specific gene polymorphisms. The model can be used to predict the concentrations of TFV-DP and FTC-TP after switching to alternative regimens.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Psychology, Clinical
Abd El Kader Ait Tayeb, Romain Colle, Kenneth Chappell, Khalil El-Asmar, Cecile Acquaviva-Bourdain, Denis J. David, Severine Trabado, Philippe Chanson, Bruno Feve, Laurent Becquemont, Celine Verstuyft, Emmanuelle Corruble
Summary: This study aimed to assess the metabolomic profiles of 38 acylcarnitines in patients with major depression before and after treatment compared to healthy controls. The results showed that depressed patients had lower levels of medium- and long-chain acylcarnitines before treatment, but these levels increased after 6 months of treatment and became similar to those of controls. Furthermore, there was a negative correlation between the levels of medium- and long-chain acylcarnitines and depression severity.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Genetics & Heredity
Daniela Matuozzo, Estelle Talouarn, Astrid Marchal, Peng Zhang, Jeremy Manry, Yoann Seeleuthner, Yu Zhang, Alexandre Bolze, Matthieu Chaldebas, Baptiste Milisavljevic, Adrian Gervais, Paul Bastard, Takaki Asano, Lucy Bizien, Federica Barzaghi, Hassan Abolhassani, Ahmad Abou Tayoun, Alessandro Aiuti, Ilad Alavi Darazam, Luis M. Allende, Rebeca Alonso-Arias, Andres Augusto Arias, Gokhan Aytekin, Peter Bergman, Simone Bondesan, Yenan T. Bryceson, Ingrid G. Bustos, Oscar Cabrera-Marante, Sheila Carcel, Paola Carrera, Giorgio Casari, Khalil Chaibi, Roger Colobran, Antonio Condino-Neto, Laura E. Covill, Ottavia M. Delmonte, Loubna El Zein, Carlos Flores, Peter K. Gregersen, Marta Gut, Filomeen Haerynck, Rabih Halwani, Selda Hancerli, Lennart Hammarstroem, Nevin Hatipoglu, Adem Karbuz, Sevgi Keles, Christele Kyheng, Rafael Leon-Lopez, Jose Luis Franco, Davood Mansouri, Javier Martinez-Picado, Ozge Metin Akcan, Isabelle Migeotte, Pierre-Emmanuel Morange, Guillaume Morelle, Andrea Martin-Nalda, Giuseppe Novelli, Antonio Novelli, Tayfun Ozcelik, Figen Palabiyik, Qiang Pan-Hammarstroem, Rebeca Perez de Diego, Laura Planas-Serra, Daniel E. Pleguezuelo, Carolina Prando, Aurora Pujol, Luis Felipe Reyes, Jacques G. Riviere, Carlos Rodriguez-Gallego, Julian Rojas, Patrizia Rovere-Querini, Agatha Schlueter, Mohammad Shahrooei, Ali Sobh, Pere Soler-Palacin, Yacine Tandjaoui-Lambiotte, Imran Tipu, Cristina Tresoldi, Jesus Troya, Diederik van de Beek, Mayana Zatz, Pawel Zawadzki, Saleh Zaid Al-Muhsen, Mohammed Faraj Alosaimi, Fahad M. Alsohime, Hagit Baris-Feldman, Manish J. Butte, Stefan N. Constantinescu, Megan A. Cooper, Clifton L. Dalgard, Jacques Fellay, James R. Heath, Yu-Lung Lau, Richard P. Lifton, Tom Maniatis, Trine H. Mogensen, Horst von Bernuth, Alban Lermine, Michel Vidaud, Anne Boland, Jean-Francois Deleuze, Robert Nussbaum, Amanda Kahn-Kirby, France Mentre, Sarah Tubiana, Guy Gorochov, Florence Tubach, Pierre Hausfater, C. O. V. I. D. Human Genetic Effort, Isabelle Meyts, Shen-Ying Zhang, Anne Puel, Luigi D. Notarangelo, Stephanie Boisson-Dupuis, Helen C. Su, Bertrand Boisson, Emmanuelle Jouanguy, Jean-Laurent Casanova, Qian Zhang, Laurent Abel, Aurelie Cobat
Summary: Through a genome-wide rare variant burden association analysis, it was found that there is an association between at-risk variants in the TLR7 gene and rare loss-of-function variants in TLR3-dependent type I interferon immunity genes. These findings suggest that rare variants in TLR3- and TLR7-dependent type I interferon immunity genes may underlie life-threatening COVID-19 in patients under 60 years old.
Review
Biochemistry & Molecular Biology
Abd El Kader Ait Tayeb, Vianney Poinsignon, Kenneth Chappell, Jerome Bouligand, Laurent Becquemont, Celine Verstuyft
Summary: Major depressive disorder (MDD) is the leading cause of global disability, but its pathophysiology is not yet fully understood, especially due to its clinical and biological heterogeneity. Oxidative stress plays a crucial role in MDD, and this narrative review identifies biomarkers of oxidative stress in MDD patients based on disease stage and clinical features. Antioxidant enzyme modifications and decreased levels of non-enzymatic antioxidants were found in MDD patients, along with increased reactive oxygen species and oxidative damage products. Interestingly, antidepressant treatment normalized these changes. This suggests the importance of oxidative stress biomarkers in MDD care and the potential for new therapeutic targets.