Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"IL-4 promotes chondrogenesis of bone marrow mesenchymal stem cells and blockade of IL-4Rα retards the endochondral ossification during rat embryonic bone development","authors":"Yimeng Hao,&nbsp;Qinghe Meng,&nbsp;Leilei Chang,&nbsp;Minglong Qiu,&nbsp;Jianxin Han,&nbsp;Zhiqin Wang,&nbsp;Changwei Li,&nbsp;Jing Ma,&nbsp;Xuemei Zhang","doi":"10.1111/bcpt.14088","DOIUrl":"10.1111/bcpt.14088","url":null,"abstract":"<p>Interleukin-4 (IL-4)/IL-4 receptor alpha (IL-4Rα) signalling pathways play important roles in the complex process of bone formation and bone remodelling. However, whether IL-4/IL-4Rα participates in skeletogenesis during embryonic development is not completely understood. We used the anti-IL-4Rα monoclonal antibody (anti-IL-4Rα mAb) as a powerful investigational tool to evaluate the potential roles of IL-4/IL-4Rα in the chondrogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) in vitro. Simultaneously, we explored the effect of IL-4/IL-4Rα on bone ossification during rat embryo-fetal development. In this study, we found that, compared to the control group, IL-4 can significantly promote the chondrogenic differentiation of BMSCs. Furthermore, following exposure to anti-IL-4Rα mAb in pregnant rats, unexpected phenomena were observed in fetal bone development, including non-ossification of the fetal sternum, an incomplete ossification centre in long bones and a reduced number of ossification points in digit (toe) bones. To further investigate the underlying mechanism of the phenotype, we studied the rat sternum as the target organ, starting from different time points of sternum development in the embryonic stage. The results indicated that the retardation mainly occurred in the middle and late stages of embryonic development. This retardation was characterized by the inhibition of the differentiation process of mesenchymal stem cells into chondrocytes, resulting in reduced angiogenesis near the ossification centre, failure of osteoblasts to invade the centre of the cartilage body with the blood vessels and delayed formation of the primary ossification centre (POC). Overall, our study demonstrated the significant function of IL-4/IL-4Rα in chondrogenic differentiation of BMSCs and bone ossification during embryo-fetal development.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 6","pages":"693-704"},"PeriodicalIF":2.7,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving CYP2C19 phenotyping using stereoselective omeprazole and 5-hydroxy-omeprazole metabolic ratios","authors":"Kenza Abouir,&nbsp;Emmanuel Varesio,&nbsp;Julien Déglon,&nbsp;Caroline Samer,&nbsp;Youssef Daali","doi":"10.1111/bcpt.14095","DOIUrl":"10.1111/bcpt.14095","url":null,"abstract":"<p>Omeprazole (OME) is a CYP2C19 phenotyping probe, marketed as a racemic <i>(S)</i>/<i>(R)</i> mixture or as an S-enantiomer. Both CYP2C19 and CYP3A4 enzymes mediate (R)-OME hydroxylation to (R)-5-hydroxyomeprazole, while (S)-OME is exclusively hydroxylated via CYP2C19. This study investigates OME and its 5-hydroxymetabolite enantiomers' pharmacokinetics using data from two studies involving healthy volunteers. In Study A, volunteers received OME alone in Session 1, OME combined with voriconazole and fluvoxamine in Session 2 and finally OME with rifampicin in Session 3. In Study B, volunteers received OME alone in Session 1, OME combined with voriconazole in Session 2 and finally OME with fluvoxamine in Session 3. Despite low metabolic ratio values of (S)-OME, detectable modulation of CYP2C19 activity suggests both (R)- and (S)-OME isomers could effectively assess CYP2C19 activity. Further research is needed for precise cut-offs in different phenotype groups.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 6","pages":"755-766"},"PeriodicalIF":2.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster","authors":"","doi":"10.1111/bcpt.14066","DOIUrl":"10.1111/bcpt.14066","url":null,"abstract":"&lt;p&gt;&lt;b&gt;#8&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Immune checkpoint inhibitors and metabolic-endocrine disorders in the US FDA adverse event reporting system: Preliminary results&lt;/b&gt;&lt;/p&gt;&lt;p&gt;G. Prada Ramallal&lt;sup&gt;1&lt;/sup&gt;, L. Romero &lt;sup&gt;2&lt;/sup&gt; and R. Nogueiras Álvarez&lt;sup&gt;3&lt;/sup&gt;&lt;/p&gt;&lt;p&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;i&gt;Clinical University Hospital of Santiago, A Coruña, Spain;&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt;&lt;i&gt;Technical Secretariat of the Medical Research Ethics Committee of Galicia (CEImG), Spain;&lt;/i&gt; &lt;sup&gt;3&lt;/sup&gt;&lt;i&gt;University Hospital Galdakao-Usansolo, Vizcaya, Spain&lt;/i&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Objective:&lt;/b&gt; Immune checkpoint inhibitors (ICIs) have gained importance in cancer treatment because of their potential to contribute to long-term remission and cure. Although the benefits outweigh the risks, potential serious side effects must be considered, such as immune-related metabolic-endocrine adverse events (AEs). These AEs may correlate with increased progression-free survival and overall survival in ICIs; however, their role as predictive biomarkers is underexplored. Our study aimed to characterize the spectrum, frequency and clinical characteristics of immune-related metabolic-endocrine AEs, as well as other non-specific AEs, associated with ICIs and reported to the FDA Adverse Event Reporting System (FAERS).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Material and/or methods:&lt;/b&gt; Data were collected from the FAERS database covering the period from the first quarter of 2012 to the fourth quarter of 2023. The definition relied on System Organ Class and Preferred Terms by the Medical Dictionary for Regulatory Activities (MedDRA). A preliminary descriptive analysis was then performed using R software (version 4.2.3). A Sankey diagram was built with the networkD3 package.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The total number of AEs in FAERS related to the selected drugs was 209 065. AEs were more common in men (53.9%) than women (34.8%). People over 65 years of age account for 40.1% of total AEs. Endocrine disorders represented 8.0% with 16 665 results. Metabolic disorders represented 9.6% with 19 983 results. The most common endocrine AEs were hypothyroidism (27.4%), adrenal insufficiency (18.6%) and hypophysitis (12.7%). The most common metabolic AEs were decreased appetite (27.9%), dehydration (12.6%) and hyponatremia (10.8%). These findings align with previous studies.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; This study explores the incidence of metabolic-endocrine AEs associated with ICIs treatment. The results show particularly high rates among older people and men. These findings provide a reliable basis for further comprehensive AEs' investigations. To establish reliable biomarkers for predicting the effectiveness of anti-tumour treatment, additional research and advanced statistical analyses are necessary.&lt;/p&gt;&lt;p&gt;&lt;b&gt;#10&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Safety of defibrotide in the prevention and treatment of acute respiratory distress syndrome in patients with COVID-19&lt;/b&gt;&lt;/p&gt;&lt;p&gt;P. Rodríguez-Fortúnez&lt;sup&gt;1&lt;/sup&gt;, A. J. Martínez-Mellado&lt;sup&gt;2&lt;/sup&gt;, R. Jara-Rubio&lt;sup&gt;2&lt;/sup&gt;, P. Castro-Rebollo&lt;sup","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 S1","pages":"25-72"},"PeriodicalIF":2.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Round tables","authors":"","doi":"10.1111/bcpt.14062","DOIUrl":"10.1111/bcpt.14062","url":null,"abstract":"&lt;p&gt;Antoni Vallano Ferraz&lt;/p&gt;&lt;p&gt;&lt;i&gt;Medicines Department, Catalan Healthcare Service, Barcelona, Spain;&lt;/i&gt; &lt;i&gt;Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Barcelona, Spain;&lt;/i&gt; &lt;i&gt;Healthcare Management of Hospitals, Catalan Institute of Health, Barcelona, Spain&lt;/i&gt;&lt;/p&gt;&lt;p&gt;The evolving landscape of drug authorization processes in the European Union (EU), with several actions to accelerate regulatory process and the access to innovative medicines, has been a response to the pressing need for increased access to innovative medicines, particularly for rare diseases, and unmet medical conditions. While this flexibility has undoubtedly expedited the availability of potentially life-saving treatments, based more in expectative that in robust evidence, it has concurrently ushered in a host of challenges that warrant careful consideration.&lt;/p&gt;&lt;p&gt;One of the foremost concerns pertains to the level of uncertainty tolerated during the approval of new medications. Notably, the approval of numerous oncological drugs based on surrogate endpoints, without concrete evidence of meaningful improvements in overall survival or quality of life, underscores the delicate balance between expediency and robust evidence. Furthermore, the emergence of additional toxicities associated with many of these approved drugs raises pertinent questions about the net clinical benefit conferred by these treatments.&lt;/p&gt;&lt;p&gt;The adoption of methodologies in clinical trials that permit early termination in response to favourable interim analyses introduces a layer of complexity, as premature cessation can inadvertently overestimate treatment effects, especially in the absence of rigorous blinding or controlled designs. This underscores the imperative for stringent scrutiny of trial data to ensure the reliability and generalizability of findings.&lt;/p&gt;&lt;p&gt;In parallel, drugs catering to niche patient populations, such as orphan medicinal products (OMPs) and advanced therapy medicinal products (ATMPs), often grapple with methodological limitations in clinical trials, resulting in approvals that are underpinned by scant evidence of efficacy and safety. This poses a considerable challenge for healthcare providers tasked with the management of the intricacies of treatment decisions in such contexts.&lt;/p&gt;&lt;p&gt;The pricing and reimbursement (P&amp;R) landscape, too, is fraught with complexities, as stakeholders endeavour to strike a delicate balance between ensuring equitable access to innovative therapies and safeguarding the fiscal sustainability of healthcare systems. Manufacturers' propensity to overestimate the cost-effectiveness of their products often leads to disparate pricing and reimbursement decisions across jurisdictions, exacerbating disparities in patient access.&lt;/p&gt;&lt;p&gt;Addressing these multifaceted challenges necessitates an approach based on multiple factors. Enhancing the scientific rigour of clinical trials through robust methodologies and tran","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 S1","pages":"9-14"},"PeriodicalIF":2.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scientific program","authors":"","doi":"10.1111/bcpt.14065","DOIUrl":"10.1111/bcpt.14065","url":null,"abstract":"&lt;p&gt;&lt;b&gt;WEDNESDAY 16 OCTOBER 2024&lt;/b&gt;&lt;/p&gt;&lt;p&gt;10:00–14:00&lt;b&gt;    ANNUAL MEETING OF RESEARCH ETHICS COMMITTEES&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Spanish Agency of Medicines and Medical Devices and Spanish Society of Clinical Pharmacology&lt;/p&gt;&lt;p&gt;15:30–18:30&lt;b&gt;    PRE-CONGRESS WORKSHOPS AND SEMINARS&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;“Next-generation of “deep” medicine: A look from machine learning to generative AI”&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Guillermo Prada Ramallal. &lt;i&gt;Clinical Pharmacologist, Hospital Clínico Universitario, Santiago de Compostela&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;Laura Romero Sánchez. &lt;i&gt;Technical Secretary of Research Ethics Committee of Galicia&lt;/i&gt;, &lt;i&gt;Gerencia del Servicio Gallego de Salud&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;b&gt;“Drafting and requesting competitive projects”&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Joaquín Sáez Peñataro. &lt;i&gt;Clinical Pharmacologist, Hospital Clínic, Barcelona&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;Paula López Vázquez. &lt;i&gt;Clinical Pharmacologist, Dirección Xeral de Asistencia Sanitaria-Servizo Galego de Saúde&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;b&gt;“Professional opportunities for the specialty of clinical pharmacology”&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Joaquín Sáez Peñataro. &lt;i&gt;Clinical Pharmacologist, Hospital Clínic, Barcelona&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;b&gt;“Evaluation of the therapeutic value of medicines: controversies and future perspectives”&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Arantxa Sancho López. &lt;i&gt;Clinical Pharmacologist, Head of Medical-Scientific Department of Farmaindustria&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;Emilio Vargas Castrillón. &lt;i&gt;Professor of Pharmacology, Head of Clinical Pharmacology Department, Hospital Clínico San Carlos, Universidad Complutense, Madrid&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;Pedro Zapater Hernández&lt;i&gt;. Head of Section of Clinical Pharmacology Department, Hospital General Universitario Dr. Balmis, Universidad Miguel Hernández, Alicante&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;Alejandro García Solís. &lt;i&gt;Therapeutic Positioning Reporting Area and Health Technology Assessment, Spanish Agency of Medicines and Medical Devices&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;b&gt;“Medicines in special situations”&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Concepción Payares Herrera. &lt;i&gt;Clinical Pharmacologist, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;Imma Danés Carreras. &lt;i&gt;Head of section of Clinical Pharmacology Department, Hospital Universitario Vall d'Hebron, Barcelona&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;19:00      &lt;b&gt;INAUGURATION OF THE CONGRESS&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Antònia Agustí Escasany. &lt;i&gt;President of the Spanish Society of Clinical Pharmacology&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;Emilio Vargas Castrillón. &lt;i&gt;President of the Organizing Committee of the XXXII Congress of the Spanish Society of Clinical Pharmacology&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;Guillermo Prada Ramallal&lt;i&gt;. President of the Scientific Committee of the XXXII Congress of the Spanish Society of Clinical Pharmacology&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;Carmen Durán. &lt;i&gt;General Director of Public Health, Consejería de Sanidad Gobierno Gallego&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;19:30&lt;b&gt;      INAUGURAL CONFERENCE&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;“Novelties in therapeutics: Advanced therapies and other innovations”&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Cristina Avendaño Solá. Head of Clinical Pharmacology Department, Hospital Puerta de Hierro, Majadahonda, Universidad Autónoma, Madrid.&lt;/p&gt;&lt;p&gt;20:30&lt;b&gt;      WELCOME COCKTAIL&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;THURSDAY 17 OCTOBER","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 S1","pages":"5-8"},"PeriodicalIF":2.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COMMITTEES","authors":"","doi":"10.1111/bcpt.14061","DOIUrl":"10.1111/bcpt.14061","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 S1","pages":"3-4"},"PeriodicalIF":2.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral Communications","authors":"","doi":"10.1111/bcpt.14063","DOIUrl":"10.1111/bcpt.14063","url":null,"abstract":"&lt;p&gt;&lt;b&gt;#44&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Late adverse events in patients treated with CAR T-cell for aggressive B-cell non-Hodgkin Lymphoma: A prospective, multicentre, real-world study&lt;/b&gt;&lt;/p&gt;&lt;p&gt;L. Camacho-Arteaga&lt;sup&gt;1,2&lt;/sup&gt;, G. Iacoboni&lt;sup&gt;1,3&lt;/sup&gt;, M. Kwon&lt;sup&gt;4,5,6&lt;/sup&gt;, R. Hernani&lt;sup&gt;7,8&lt;/sup&gt;, L. López-Corral&lt;sup&gt;9,10&lt;/sup&gt;, L. M. Leguízamo-Martínez&lt;sup&gt;11,12,13&lt;/sup&gt;, M. Guerreiro&lt;sup&gt;14&lt;/sup&gt;, C. Alonso-Martínez&lt;sup&gt;1&lt;/sup&gt;, P. Barba&lt;sup&gt;1,3,2&lt;/sup&gt; and A. Agustí&lt;sup&gt;1,2&lt;/sup&gt;&lt;/p&gt;&lt;p&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;i&gt;Hospital Universitari Vall d'Hebron, Barcelona, Spain;&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt;&lt;i&gt;Universitat Autònoma de Barcelona, Barcelona, Spain;&lt;/i&gt; &lt;sup&gt;3&lt;/sup&gt;&lt;i&gt;Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain;&lt;/i&gt; &lt;sup&gt;4&lt;/sup&gt;&lt;i&gt;Hospital General Universitario Gregorio Marañón, Madrid, Spain;&lt;/i&gt; &lt;sup&gt;5&lt;/sup&gt;&lt;i&gt;Institute of Health Resarch Gregorio Marañón, Madrid, Spain;&lt;/i&gt; &lt;sup&gt;6&lt;/sup&gt;&lt;i&gt;Universidad Complutense de Madrid, Madrid, Spain;&lt;/i&gt; &lt;sup&gt;7&lt;/sup&gt;&lt;i&gt;Hospital Clínico Universitario, Valencia, Spain;&lt;/i&gt; &lt;sup&gt;8&lt;/sup&gt;&lt;i&gt;INCLIVA Research Institute, Valencia, Spain;&lt;/i&gt; &lt;sup&gt;9&lt;/sup&gt;&lt;i&gt;Hospital Universitario de Salamanca, IBSAL, CIBERONC, Salamanca, Spain;&lt;/i&gt; &lt;sup&gt;10&lt;/sup&gt;&lt;i&gt;Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca, Spain;&lt;/i&gt; &lt;sup&gt;11&lt;/sup&gt;&lt;i&gt;Hospital Clinic of Barcelona, Barcelona, Spain;&lt;/i&gt; &lt;sup&gt;12&lt;/sup&gt;&lt;i&gt;Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain;&lt;/i&gt; &lt;sup&gt;13&lt;/sup&gt;&lt;i&gt;Universitat de Barcelona, Barcelona, Spain;&lt;/i&gt; &lt;sup&gt;14&lt;/sup&gt;&lt;i&gt;Hospital Universitari i Politecnic La Fe, Valencia, Spain&lt;/i&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Objective&lt;/b&gt;: Acute adverse events after CAR T-cell infusion are well known, but less information is available about long-term toxicities and their incidence. Our research aimed to describe the occurrence of any late adverse event (AE) in patients with an aggressive B-cell non-Hodgkin lymphoma (NHL) treated with CD19 CAR-T cells.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Material and/or methods&lt;/b&gt;: A prospective, observational study was carried out in six Spanish centres from 1 September 2018 to 31 December 2022. All adult patients diagnosed with an aggressive B-cell NHL treated with a commercial CAR T-cell product (tisagenlecleucel or axicabtagene ciloleucel) who had not received any other treatment for their disease at 3 months post-infusion were included. Late AEs were defined as those that either persisted or occurred beyond 3 months post-infusion. Incidence and severity of late AE episodes were analysed.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results&lt;/b&gt;: A total of 172 infused patients were evaluated with a median follow-up of 13.9 months (IQR8.2–23.8). One hundred thirty-five (78.5%) patients experienced at least one late AE of any grade, being infection episodes with an incidence of 5.63 per 100 person-months, [CI 95% 4.50–7.04], the most frequent, followed by neutropenia (3.59 per 100 person-months [CI 95% 2.89–4.53]) and thrombocytopenia (2.24 per 100 person-months [CI 95% 1.65–3.02]). There were no differences in the late AEs incidence betwee","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 S1","pages":"15-24"},"PeriodicalIF":2.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An overview of major depression disorder: The endocannabinoid system as a potential target for therapy","authors":"Sergio Zarazúa-Guzmán,&nbsp;Jorge Genaro Vicente-Martínez,&nbsp;Juan Manuel Pinos-Rodríguez,&nbsp;Jaime Iván Arevalo-Villalobos","doi":"10.1111/bcpt.14089","DOIUrl":"10.1111/bcpt.14089","url":null,"abstract":"<p>Major depressive disorder is the psychiatric disease with the highest global prevalence, impacting social functioning and decreasing the quality of life. The partial pathophysiological knowledge of the disease, the economic burden and the low remission rates are sufficient justification to carry out an update on the subject in the search for new therapeutic approaches and targets. The endocannabinoid system has been linked to the development of depression, and its stimulation or antagonism is a promising approach in the treatment of major depressive disorder. Cannabidiol (CBD) and its properties have been widely studied recently; its analgesic, anti-inflammatory, antineoplastic and neuroprotective roles have even been reported in animal models and clinical trials, achieving its approved use for certain neurodegenerative pathologies. The use of CBD in depression biomodels and clinical trials has not been the exception, and here we contrast the current evidence of its administration and pharmacology against the pathological mechanisms of major depressive disorder.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 6","pages":"669-684"},"PeriodicalIF":2.7,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxicity, genotoxicity and mutagenicity of mixed ternary mononuclear Mg complex based on valproic acid with 1,10-phenanthroline in Saccharomyces cerevisiae and V79 cells","authors":"Julia Vanini,&nbsp;Gabriel Berbigier Rodrigues,&nbsp;André Luiz Mendes Juchem,&nbsp;Temenouga Nikolova Guecheva,&nbsp;Sidnei Moura,&nbsp;Françoise Dumas,&nbsp;João Antonio Pêgas Henriques,&nbsp;Iuri Marques de Oliveira","doi":"10.1111/bcpt.14091","DOIUrl":"10.1111/bcpt.14091","url":null,"abstract":"<p>Valproic acid (VA) is a widely used drug for the treatment of diseases affecting the central nervous system. Due to its epigenetic modulatory potential, it has been studied for possible therapeutic application in anticancer therapies. However, the VA exhibits different side effects in its application. Thus, synthetic coordination complexes with valproate can generate promising candidates for new active drugs with reduced toxicity. In this sense, we investigated the genotoxic and mutagenic potential of the sodium valproate and of the mixed ternary mononuclear Mg complex based on VA with 1,10-phenanthroline (Phen) ligand - [Mg (Valp)₂Phen], in <i>Saccharomyces cerevisiae</i> and V79 cells. The MTT and clonal survival assays in V79 cells indicated that the Mg complex has higher cytotoxicity than sodium valproate. A similar cytotoxicity profile is observed in yeast. This fact is possibly due to the intercalation capacity of [Mg(Valp)₂Phen], inducing DNA strand breaks, as observed in the comet assay and micronucleus test. In this sense, members of the NER, HR, NHEJ and TLS repair pathways are required for the repair of DNA lesions induced by [Mg(Valp)₂Phen]. Interestingly, BER proteins apparently increase the cytotoxic potential of the drug. Furthermore, the [Mg(Valp)₂Phen] showed higher cytotoxicity in V79 cells and yeast when compared to sodium valproate indicating applicability as a cytotoxic agent.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 6","pages":"767-781"},"PeriodicalIF":2.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Epigallocatechin-3-gallate(−) protects Chang liver cells against ethanol-induced cytotoxicity and apoptosis","authors":"","doi":"10.1111/bcpt.14086","DOIUrl":"10.1111/bcpt.14086","url":null,"abstract":"<p><b>RETRACTION</b>: S. Kaviarasan, N. Ramamurthy, P. Gunasekaran, E. Varalakshmi and C. V. Anuradha, “Epigallocatechin-3-gallate(-) Protects Chang Liver Cells against Ethanol-induced Cytotoxicity and Apoptosis,” <i>Basic &amp; Clinical Pharmacology &amp; Toxicology</i> 100, No. 3 (2007): 151–156, https://doi.org/10.1111/j.1742-7843.2006.00036.x.</p><p>The above article, published online on 16 January 2007 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editors-in-Chief, Jens Lykkesfeldt and Ulf Simonsen; the Nordic Association for the Publication of BCPT (formerly the Nordic Pharmacological Society); and John Wiley &amp; Sons Ltd. The retraction has been agreed due to concerns that the images presented in Figure 2a–c are duplicates of images published earlier by the same author group in another journal. Although two of the duplicate images appear to represent the same experiment, the image presented in Figure 2c of this article represents a different treatment to that of the duplicate image in the earlier article. Furthermore, several of the control and EtOH values presented in Table 1 and the flow cytometry panels presented in Figure 3a,b are identical to those shown in the earlier article. As a result, the editors consider the results and conclusions of this article to be invalid. The authors were informed of the decision to retract; however, all but one were unavailable for comment. Elango Varalakshmi stated that she did not consent to be listed as an author for this publication.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 5","pages":"664"},"PeriodicalIF":2.7,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}