首页 > 最新文献

Basic & Clinical Pharmacology & Toxicology最新文献

英文 中文
Correction to ‘register-based study on prescription renewal without the prescriber meeting the patient’ 更正为 "基于登记册的处方续订研究,处方开具人未与患者见面
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-13 DOI: 10.1111/bcpt.14093

Rönngård-Jalkanen, A, Aarnio, E, Saastamoinen, L, Timonen, J. Register based study on prescription renewal without the prescriber meeting the patient. Basic Clin Pharmacol Toxicol 2024; 135(3): 321-333. doi:10.1111/bcpt.14049

In the above article, the Data Availability Statement is shown as ‘The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethics restrictions’.

The correct statement should be

We apologize for this error.

Rönngård-Jalkanen,A,Aarnio,E,Saastamoinen,L,Timonen,J. 在处方者未与患者见面的情况下进行处方更新的登记研究。Basic Clin Pharmacol Toxicol 2024; 135(3):321-333.doi:10.1111/bcpt.14049在上述文章中,数据可用性声明显示为 "支持本研究结果的数据可向通讯作者索取。由于隐私或伦理方面的限制,这些数据不对外公开"。正确的声明应为:我们对这一错误表示歉意。
{"title":"Correction to ‘register-based study on prescription renewal without the prescriber meeting the patient’","authors":"","doi":"10.1111/bcpt.14093","DOIUrl":"https://doi.org/10.1111/bcpt.14093","url":null,"abstract":"<p>\u0000 <span>Rönngård-Jalkanen, A</span>, <span>Aarnio, E</span>, <span>Saastamoinen, L</span>, <span>Timonen, J</span>. <span>Register based study on prescription renewal without the prescriber meeting the patient</span>. <i>Basic Clin Pharmacol Toxicol</i> <span>2024</span>; <span>135</span>(<span>3</span>): <span>321</span>-<span>333</span>. doi:10.1111/bcpt.14049</p><p>In the above article, the Data Availability Statement is shown as ‘The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethics restrictions’.</p><p>The correct statement should be</p><p>We apologize for this error.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 5","pages":"665"},"PeriodicalIF":2.7,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443535","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}
引用次数: 0
IL-4 promotes chondrogenesis of bone marrow mesenchymal stem cells and blockade of IL-4Rα retards the endochondral ossification during rat embryonic bone development IL-4能促进骨髓间充质干细胞的软骨形成,阻断IL-4Rα能延缓大鼠胚胎骨骼发育过程中的软骨内骨化。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-13 DOI: 10.1111/bcpt.14088
Yimeng Hao, Qinghe Meng, Leilei Chang, Minglong Qiu, Jianxin Han, Zhiqin Wang, Changwei Li, Jing Ma, Xuemei Zhang

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.

白细胞介素-4(IL-4)/IL-4受体α(IL-4Rα)信号通路在复杂的骨形成和骨重塑过程中发挥着重要作用。然而,IL-4/IL-4Rα是否参与胚胎发育过程中的骨骼形成还不完全清楚。我们使用抗IL-4Rα单克隆抗体(抗IL-4Rα mAb)作为一种强大的研究工具,在体外评估IL-4/IL-4Rα在大鼠骨髓间充质干细胞(BMSCs)软骨分化中的潜在作用。同时,我们还探讨了IL-4/IL-4Rα对大鼠胚胎-胎儿发育过程中骨骨化的影响。研究发现,与对照组相比,IL-4 能显著促进 BMSCs 的软骨分化。此外,妊娠大鼠暴露于抗IL-4Rα mAb后,在胎儿骨骼发育过程中观察到了意想不到的现象,包括胎儿胸骨不骨化、长骨骨化中心不完整以及指(趾)骨骨化点数量减少。为了进一步研究这种表型的内在机制,我们以大鼠胸骨为靶器官,从胚胎期胸骨发育的不同时间点入手进行了研究。结果表明,胸骨发育迟缓主要发生在胚胎发育的中后期。这种发育迟缓的特点是间充质干细胞向软骨细胞的分化过程受到抑制,导致骨化中心附近的血管生成减少,成骨细胞不能随血管侵入软骨体中心,初级骨化中心(POC)的形成延迟。总之,我们的研究证明了IL-4/IL-4Rα在胚胎-胎儿发育过程中对BMSCs软骨分化和骨化的重要作用。
{"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}
引用次数: 0
Improving CYP2C19 phenotyping using stereoselective omeprazole and 5-hydroxy-omeprazole metabolic ratios 利用立体选择性奥美拉唑和 5-羟基奥美拉唑代谢比率改进 CYP2C19 表型分析。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-09 DOI: 10.1111/bcpt.14095
Kenza Abouir, Emmanuel Varesio, Julien Déglon, Caroline Samer, Youssef Daali

Omeprazole (OME) is a CYP2C19 phenotyping probe, marketed as a racemic (S)/(R) 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.

奥美拉唑(OME)是一种 CYP2C19 表型探针,以外消旋(S)/(R)混合物或 S-对映体的形式销售。CYP2C19 和 CYP3A4 两种酶均介导 (R)-OME 羟化成 (R)-5-羟基奥美拉唑,而 (S)-OME 则完全通过 CYP2C19 羟化。本研究利用两项涉及健康志愿者的研究数据,对 OME 及其 5-羟基代谢物对映体的药代动力学进行了调查。在研究 A 中,志愿者在第一阶段单独服用了奥美拉唑,在第二阶段与伏立康唑和氟伏沙明合用了奥美拉唑,最后在第三阶段与利福平合用了奥美拉唑。在研究 B 中,志愿者在第一环节只接受奥美拉唑治疗,在第二环节接受奥美拉唑与伏立康唑联合治疗,最后在第三环节接受奥美拉唑与氟伏沙明联合治疗。尽管(S)-OME的代谢比值较低,但可检测到对CYP2C19活性的调节,这表明(R)-和(S)-OME异构体均可有效评估CYP2C19活性。需要进一步研究不同表型组的精确临界值。
{"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}
引用次数: 0
Poster 西班牙临床药理学学会第三十二届大会,2024 年 10 月 16-18 日,西班牙圣地亚哥德孔波斯特拉。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-08 DOI: 10.1111/bcpt.14066
<p><b>#8</b></p><p><b>Immune checkpoint inhibitors and metabolic-endocrine disorders in the US FDA adverse event reporting system: Preliminary results</b></p><p>G. Prada Ramallal<sup>1</sup>, L. Romero <sup>2</sup> and R. Nogueiras Álvarez<sup>3</sup></p><p><sup>1</sup><i>Clinical University Hospital of Santiago, A Coruña, Spain;</i> <sup>2</sup><i>Technical Secretariat of the Medical Research Ethics Committee of Galicia (CEImG), Spain;</i> <sup>3</sup><i>University Hospital Galdakao-Usansolo, Vizcaya, Spain</i></p><p><b>Objective:</b> 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).</p><p><b>Material and/or methods:</b> 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.</p><p><b>Results:</b> 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.</p><p><b>Conclusions:</b> 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.</p><p><b>#10</b></p><p><b>Safety of defibrotide in the prevention and treatment of acute respiratory distress syndrome in patients with COVID-19</b></p><p>P. Rodríguez-Fortúnez<sup>1</sup>, A. J. Martínez-Mellado<sup>2</sup>, R. Jara-Rubio<sup>2</sup>, P. Castro-Rebollo<sup
由于招募人数较少,CT 从 HUMV 的单中心试验改为多中心试验,增加了两个试验点。自2022年3月以来,共招募了14名患者;在单一生产中心实施多中心试验,需要在药品生产后进行物流运输,并集中管理样本:结论:对于学术 CT 而言,有坚实和最新科学依据支持的适当设计至关重要。83一项试点、随机、三臂、剂量调查、安慰剂对照、平行研究,以评估使用纳比西莫司(四氢大麻酚 + CBD,Sativex®)进行大麻解毒治疗与常规治疗的对比D.Martínez Bonifacio1、M. Puntes Rodríguez1、P. Molina Perelló1、J. Coimbra Hurtado1、J. Trujols Albet2、X. Roca Tutusaus2 和 R. M. Antonijoan Arbós。Antonijoan Arbós1,31Centre Investigació Medicament (CIM) Institut de Recerca Sant Pau, Barcelona, Spain; 2Department of Psychiatry, Hospital Sant Pau, Barcelona, Spain; 3Department of Clinical Pharmacology, Hospital Sant Pau, Barcelona, SpainObjective:本研究旨在评估纳比西莫司(四氢大麻酚 + CBD,Sativex®)以两种不同剂量与常规治疗相比在减轻大麻依赖者戒断症状方面的效果:16 名寻求住院戒毒的大麻依赖者参加了这项平行、随机、单盲和安慰剂对照临床研究。在为期 9 天的研究中,受试者接受了纳比西莫司(四氢大麻酚 + CBD,Sativex®)低剂量 + 常规治疗;纳比西莫司高剂量 + 常规治疗;或安慰剂 + 常规治疗。戒断症状和渴求分别使用大麻戒断量表(CWS)和大麻渴求视觉模拟量表(VAS-CC)进行评估。CWS 在基线和治疗后第 1-9 天进行测量。主要终点是各组戒断症状和渴求程度与基线相比的平均值。在基线、+26 h和+228 h对血液进行分析,以评估CBD、THC和OH-THC的血浆水平:结果:在 CWS 测试中,与基线的平均结果相比,高剂量(-1.09)比低剂量(-0.86)和安慰剂(-0.54)的降低幅度更大。在 VAS-CC 测试中,与低剂量和安慰剂相比,高剂量的结果有所改善,数值分别为-52.5、-13.77 和-24.55。在药代动力学数据方面,观察到血浆水平与两项测试得分的降低之间存在相关性。这些结果成反比;一个增加,另一个减少:纳比昔莫司可以减轻大麻依赖患者的戒断症状和戒毒渴求。具体来说,与低剂量和安慰剂相比,高剂量的拿比锡莫司能更大程度地减轻戒断症状。高剂量组表现出最显著的改善,表明剂量-反应关系与所获得的血浆结果一致:酒精浓度和影响的性别差异M.Farré Albaladejo、C. Pérez Mañá、O. Hladun Alvaro、G. De La Rosa Loppacher、D. A. Caicedo、M. C. Argote Oramas、M. M. Anleu De León、S. Martin Sánchez、L. Poyatos Blanco 和 E. Papaseit Fontanet。西班牙巴塞罗那 Autònoma de Barcelona 大学 Trias i Pujol-IGTP 医院临床药理学系:酗酒(BD)是青少年/年轻成年人中一种成熟的饮酒模式,意在醉酒。它是指在短时间内(2 小时)大量饮酒,女性通常在喝完四杯标准酒(40 克),男性通常在喝完五杯标准酒(50 克)后,血液中的酒精浓度(BAC)达到 0.8 克/升,相当于呼出的酒精浓度(BrAC)达到 0.4 毫克/升。在之前的研究中,我们证明在 80 分钟和 120 分钟内饮酒后会出现类似的暴饮暴食现象:研究采用随机、交叉、双重对照和安慰剂对照的方法。我们纳入了 24 名志愿者。女性口服 55 克酒精或安慰剂(10 人),男性口服 70 克酒精或安慰剂(14 人),持续 45 分钟(5 杯,总容量 700 毫升)。研究变量包括生命体征、主观效果(视觉模拟量表(VAS))和 10 小时内测量的 BrAC:结果:饮酒对男女都会产生 BD 发作。两性的酒精浓度(BraCA Cmax 0.62 mg/L)和急性酒精效应(醉酒)相似,但女性的负面效应高于男性。
{"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}
引用次数: 0
Round tables 西班牙临床药理学学会第三十二届大会,2024 年 10 月 16-18 日,西班牙圣地亚哥德孔波斯特拉。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-08 DOI: 10.1111/bcpt.14062
<p>Antoni Vallano Ferraz</p><p><i>Medicines Department, Catalan Healthcare Service, Barcelona, Spain;</i> <i>Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Barcelona, Spain;</i> <i>Healthcare Management of Hospitals, Catalan Institute of Health, Barcelona, Spain</i></p><p>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.</p><p>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.</p><p>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.</p><p>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.</p><p>The pricing and reimbursement (P&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.</p><p>Addressing these multifaceted challenges necessitates an approach based on multiple factors. Enhancing the scientific rigour of clinical trials through robust methodologies and tran
另一个需要考虑的方面是目前可用的大量健康数据。这包括医疗记录、DNA 数据、图像和来自手机健康应用程序的数据。因此,有必要开发能够安全处理这些海量数据的系统,并识别出对我们的健康有用和关键的信息。在全民个人层面利用人工智能与在医疗保健等高风险领域全面部署人工智能之间仍存在巨大差距。虽然在人工智能的应用方面有许多成功的研究,但研究人员的建议与在医疗系统中的实施之间仍有很大差距。由欧盟资助的一项研究[1]对医疗保健生态系统中的主要参与者进行了调查,其中包括医疗保健专业人士、初创公司的经理和顾问。该报告的主要结论之一是,将人工智能融入医疗保健系统不会导致取代医疗保健专业人员。相反,它将增强专业人员影响患者和医疗系统的能力。将人工智能引入医疗保健系统将使这成为可能,这将使医疗保健专业人员能够专注于病人,花更少的时间在行政任务上,花更多的时间在直接提供护理上。预计某些活动将变得更有效率和/或产生更好的结果。预计智能机器还将承担更多的体力、重复性和基本认知任务。此外,还假定到医院就诊的普通病人将有更复杂的需求。最后,假设医疗保健领域将接受并整合具备人工智能和数据科学专业知识的新专业人员。报告的第二部分探讨了促进在医疗保健领域引入和推广人工智能所需的必要变革。它确定了八个关键行动点,包括需要合作以在医疗保健领域提供高质量的人工智能、重新思考教育和技能、加强数据质量、治理、安全性和互操作性、管理变革、投资于新人才和创造新角色、规模化工作、监管、政策制定和问责制以及风险管理和资金。这与西班牙众议院科技办公室于 2022 年 11 月发布的人工智能与健康报告[2]一致,该报告指出了在医疗保健系统中实现可信人工智能所面临的挑战。这些挑战包括开发高质量和无偏见的数据库、开发可靠和安全的人工智能系统、建立明确的监管框架、系统的可解释性和可靠性以及医疗保健系统工作人员的专业转型。总之,虽然已经采取了初步措施将人工智能融入医疗保健系统,但政府必须发挥领导作用,以确保这一实施是安全、可靠和全民可及的。此外,使用该技术的患者和大学医学生都迫切需要掌握必要的知识,以便驾驭人工智能驱动的医疗保健的复杂性。 用人工智能改造医疗保健。对劳动力和组织的影响。 https://eithealth.eu/think-tank-topic/artificial-intelligence-in-healthcare/ (consultado 12-june-2024).[2] Oficina de Ciencia y Tecnología del Congreso de los Diputados. Informe C: Inteligencia artificial y salud. 2022.DOI:10.57952/tcsx-b678.
{"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}
引用次数: 0
Scientific program 西班牙临床药理学学会第三十二届大会,2024 年 10 月 16-18 日,西班牙圣地亚哥德孔波斯特拉。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-08 DOI: 10.1111/bcpt.14065
<p><b>WEDNESDAY 16 OCTOBER 2024</b></p><p>10:00–14:00<b>    ANNUAL MEETING OF RESEARCH ETHICS COMMITTEES</b></p><p>Spanish Agency of Medicines and Medical Devices and Spanish Society of Clinical Pharmacology</p><p>15:30–18:30<b>    PRE-CONGRESS WORKSHOPS AND SEMINARS</b></p><p><b>“Next-generation of “deep” medicine: A look from machine learning to generative AI”</b></p><p>Guillermo Prada Ramallal. <i>Clinical Pharmacologist, Hospital Clínico Universitario, Santiago de Compostela</i>.</p><p>Laura Romero Sánchez. <i>Technical Secretary of Research Ethics Committee of Galicia</i>, <i>Gerencia del Servicio Gallego de Salud</i>.</p><p><b>“Drafting and requesting competitive projects”</b></p><p>Joaquín Sáez Peñataro. <i>Clinical Pharmacologist, Hospital Clínic, Barcelona</i>.</p><p>Paula López Vázquez. <i>Clinical Pharmacologist, Dirección Xeral de Asistencia Sanitaria-Servizo Galego de Saúde</i>.</p><p><b>“Professional opportunities for the specialty of clinical pharmacology”</b></p><p>Joaquín Sáez Peñataro. <i>Clinical Pharmacologist, Hospital Clínic, Barcelona</i>.</p><p><b>“Evaluation of the therapeutic value of medicines: controversies and future perspectives”</b></p><p>Arantxa Sancho López. <i>Clinical Pharmacologist, Head of Medical-Scientific Department of Farmaindustria</i>.</p><p>Emilio Vargas Castrillón. <i>Professor of Pharmacology, Head of Clinical Pharmacology Department, Hospital Clínico San Carlos, Universidad Complutense, Madrid</i>.</p><p>Pedro Zapater Hernández<i>. Head of Section of Clinical Pharmacology Department, Hospital General Universitario Dr. Balmis, Universidad Miguel Hernández, Alicante</i>.</p><p>Alejandro García Solís. <i>Therapeutic Positioning Reporting Area and Health Technology Assessment, Spanish Agency of Medicines and Medical Devices</i>.</p><p><b>“Medicines in special situations”</b></p><p>Concepción Payares Herrera. <i>Clinical Pharmacologist, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid</i>.</p><p>Imma Danés Carreras. <i>Head of section of Clinical Pharmacology Department, Hospital Universitario Vall d'Hebron, Barcelona</i>.</p><p>19:00      <b>INAUGURATION OF THE CONGRESS</b></p><p>Antònia Agustí Escasany. <i>President of the Spanish Society of Clinical Pharmacology</i>.</p><p>Emilio Vargas Castrillón. <i>President of the Organizing Committee of the XXXII Congress of the Spanish Society of Clinical Pharmacology</i>.</p><p>Guillermo Prada Ramallal<i>. President of the Scientific Committee of the XXXII Congress of the Spanish Society of Clinical Pharmacology</i>.</p><p>Carmen Durán. <i>General Director of Public Health, Consejería de Sanidad Gobierno Gallego</i>.</p><p>19:30<b>      INAUGURAL CONFERENCE</b></p><p><b>“Novelties in therapeutics: Advanced therapies and other innovations”</b></p><p>Cristina Avendaño Solá. Head of Clinical Pharmacology Department, Hospital Puerta de Hierro, Majadahonda, Universidad Autónoma, Madrid.</p><p>20:30<b>      WELCOME COCKTAIL</b></p><p><b>THURSDAY 17 OCTOBER
安东尼奥-卡尔卡斯-桑苏安马德里拉巴斯大学医院.Alberto Borobia Pérez.马德里拉巴斯大学医院.Cristina Avendaño Sola.马德里马亚达洪达 Puerta de Hierro 大学医院.Francisco Abad Santos.14:00-15:30 午餐15:30-17:00 第二场圆桌会议 "慢性病、多种疗法和健康结果 "主持人:Mª Estrella Barceló Colomer.加泰罗尼亚健康研究所巴塞罗那市初级医疗管理和社区医疗医学领域临床药理学家。Gerencia de Atención Primaria del Servicio Cántabro de Salud 初级医疗临床药理学部临床药理学家。15:35-15:55 "慢性病和多重用药的流行病学 "Arturo González Quintela.内科专家,圣地亚哥-德孔波斯特拉大学医院内科主任。15:55-16:15 "多重用药和停药 "比阿特丽斯-蒙特罗-埃拉斯金。16:15-16:35 "多药治疗慢性病患者的健康状况 "Rosendo Bugarín González.家庭医生,Monforte de Lemos 健康中心,Servicio Galego de Saúde.16:35-17:00:35-17:00 讨论17:00-17:30 茶歇、海报展和网络交流17:30-19:30 西班牙临床药理学会大会21:00 大会晚宴202 年 10 月 18 日星期四9:00-10:30 第二场口头交流主持:玛丽亚-德尔-玛-加西亚-赛伊斯。桑坦德 Marqués de Valdecilla 大学医院临床药理学部主任。10:30-11:00 茶歇、海报展和网络交流11:00-13:00 第三圆桌会议 "人工智能在医学中的应用:技术、研究、教育和伦理 "主持人:埃米利奥-巴尔加斯-卡斯特里隆(Emilio Vargas Castrillón)。马德里康普斯顿大学圣卡洛斯医院临床药理学系主任、药理学教授。11:05-11:25 "生成式人工智能在医学中的应用 "Senén Barro Ameneiro.11:25-11:45 "人工智能在药物流行病学研究中的应用:米格尔-安赫尔-马西亚-马丁内斯(Miguel Ángel Maciá Martínez)。公共卫生系统数据库药物流行病学研究协调员,西班牙药品和医疗器械管理局药物流行病学和药物警戒司药物流行病学领域负责人。11:45-12:05 "在医疗保健领域广泛应用人工智能的挑战 "Maria José Carreira Nouche.圣地亚哥-德孔波斯特拉大学智能技术独特研究中心,圣地亚哥-德孔波斯特拉卫生研究所基金会:监管与伦理 "胡安-迪亚斯-加西亚。预防医学和公共卫生数据专家,安达卢西亚公共卫生系统保护官员,安达卢西亚生物医学研究伦理协调委员会成员。12:25-13:00 讨论13:00-13:30 闭幕会议 "批准药品所需的证据:我们是否正在见证范式的转变?"费尔南多-德安德烈斯-特雷利斯。马德里康普斯顿大学药理学和毒理学系名誉教授。13:30-14:00 颁奖和闭幕式最佳研究工作奖(最佳交流奖),由西班牙 Chiesi 公司赞助。最佳科学期刊论文奖,由礼来公司赞助。西班牙临床药理学会主席。西班牙临床药理学会第三十二届大会组委会主席。西班牙临床药理学会第三十二届大会科学委员会主席。加列戈政府卫生委员会公共卫生总监。
{"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}
引用次数: 0
COMMITTEES 西班牙临床药理学学会第三十二届大会,2024 年 10 月 16-18 日,西班牙圣地亚哥德孔波斯特拉。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-08 DOI: 10.1111/bcpt.14061
{"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}
引用次数: 0
Oral Communications 西班牙临床药理学学会第三十二届大会,2024 年 10 月 16-18 日,西班牙圣地亚哥德孔波斯特拉。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-08 DOI: 10.1111/bcpt.14063
<p><b>#44</b></p><p><b>Late adverse events in patients treated with CAR T-cell for aggressive B-cell non-Hodgkin Lymphoma: A prospective, multicentre, real-world study</b></p><p>L. Camacho-Arteaga<sup>1,2</sup>, G. Iacoboni<sup>1,3</sup>, M. Kwon<sup>4,5,6</sup>, R. Hernani<sup>7,8</sup>, L. López-Corral<sup>9,10</sup>, L. M. Leguízamo-Martínez<sup>11,12,13</sup>, M. Guerreiro<sup>14</sup>, C. Alonso-Martínez<sup>1</sup>, P. Barba<sup>1,3,2</sup> and A. Agustí<sup>1,2</sup></p><p><sup>1</sup><i>Hospital Universitari Vall d'Hebron, Barcelona, Spain;</i> <sup>2</sup><i>Universitat Autònoma de Barcelona, Barcelona, Spain;</i> <sup>3</sup><i>Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain;</i> <sup>4</sup><i>Hospital General Universitario Gregorio Marañón, Madrid, Spain;</i> <sup>5</sup><i>Institute of Health Resarch Gregorio Marañón, Madrid, Spain;</i> <sup>6</sup><i>Universidad Complutense de Madrid, Madrid, Spain;</i> <sup>7</sup><i>Hospital Clínico Universitario, Valencia, Spain;</i> <sup>8</sup><i>INCLIVA Research Institute, Valencia, Spain;</i> <sup>9</sup><i>Hospital Universitario de Salamanca, IBSAL, CIBERONC, Salamanca, Spain;</i> <sup>10</sup><i>Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca, Spain;</i> <sup>11</sup><i>Hospital Clinic of Barcelona, Barcelona, Spain;</i> <sup>12</sup><i>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain;</i> <sup>13</sup><i>Universitat de Barcelona, Barcelona, Spain;</i> <sup>14</sup><i>Hospital Universitari i Politecnic La Fe, Valencia, Spain</i></p><p><b>Objective</b>: 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.</p><p><b>Material and/or methods</b>: 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.</p><p><b>Results</b>: 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
共对 952 份样本进行了分析,其中 6% 的样本出现了突变。2023 年 1 月至 2024 年 5 月期间,共收到 834 份样本用于研究 DPYD 基因(6% 出现突变)。临床药理学纳入了治疗调整/修改建议。此外,还对患者进行了 23 项研究,以分析其他基因(CYP2C19、CYP2C9、CYP2D6 TPMT-NUDT15、SLCO1B1)。精神健康(46%)和消化系统(17%)是主要申请者。共分析了 78 个基因(28% 为突变基因)。根据指南(CPIC、DPWG、SEFF)的临床建议,CYP2C19变异数量最多,为1A级:结论:在多学科参与下编写报告可改进对基因结果的解释,并提供更准确的临床建议,包括对相互作用等其他因素的评估。将禁忌症/处方修改提醒纳入病历有助于提高患者的安全性。#42接受 GLP-1 类似物治疗的 2 型糖尿病患者生活质量的变化C.Roca Martínez1、P. M. López Vázquez2、A. Salgado Barreira1、J. R. González Juanatey3 和 J. Seijas Amigo31美国加州大学洛杉矶分校。Seijas Amigo31Universidade de Santiago de Compostela, Santiago, Spain; 2Servicio Galego de Saúde, Dirección Xeral Asistencia Sanitaria, Santiago, Spain; 3Servicio de Cardiología, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago, SpainObjective:评估 GLP-1 类似物对患者整体健康的影响,重点关注生活质量的变化:在 13 家医疗中心开展了一项观察研究。研究对象包括开始接受 aGLP-1 治疗的 2 型糖尿病和肥胖症患者。进行了为期 44 周的随访,包括在研究开始和结束时测量人体测量参数(体重指数、腹部直径和体重变化)、实验室参数(葡萄糖、HbA1c、肌酐、c-LDL、非 HDL、c-HDL 和甘油三酯)以及两份生活质量问卷(EQ-5D-5L 和 SF-12)。研究获得了加利西亚伦理委员会的批准:共纳入 135 名受试者(54% 为男性,平均年龄 61.5 岁)。28.9%的患者接受了皮下注射的塞马鲁肽,31.1%接受了口服塞马鲁肽,34.8%接受了度拉鲁肽,5.2%接受了其他药物(利拉鲁肽和艾塞那肽)。多项实验室指标、体重指数、腹部直径和体重均有显著改善。初始评分和第44周评分显示,EQ-5D指数(0.7 ± 0.2 vs. 0.8 ± 0.2; p &lt; 0.001)、EQ-VAS(58.3 ± 22.4 vs. 65.3 ± 21.3; p &lt; 0.01)和 SF-12 身体部分得分(PCS)(39.8 ± 11.6 vs. 44.5 ± 12;p &lt;0.001),但 SF-12 精神部分得分(MCS)(49.4 ± 12.9 vs. 52.3 ± 11.5;p = 0.146)则没有变化。亚组分析显示,只有口服塞马鲁肽的患者在治疗44周后,EQ-VAS(p = 0.045)和EQ-5D(p = 0.005)有显著改善:结论:GLP-1 类似物在现实生活中能明显改善 2 型糖尿病和肥胖症患者的生活质量和临床疗效。Puñet Valls1,2, M. Umbria Vivancos1, G. Puig Comas1,2, J. M. Fontanet Sacristán1,2, M. Gasol Boncompte1,2 and A. Vallano Ferraz1,3,21Servei Català de la Salut, Barcelona, Spain; 2Universitat Autònoma de Barcelona, Barcelona, Spain; 3Institut Català de Salut, Barcelona, SpainObjective:个性化肿瘤学是由特定肿瘤分子改变的识别所驱动的,它已导致精准肿瘤药物的商业化。本研究探讨了与精准肿瘤治疗相关的处方模式和相关支出的演变:我们进行了一项观察性、回顾性队列研究,分析了加泰罗尼亚卫生服务机构在 2013 年至 2023 年期间对实体瘤进行精准肿瘤治疗的情况。研究使用了加泰罗尼亚医疗服务机构患者和治疗登记处(RPT)的数据,以收集有关接受治疗的患者、肿瘤、可采取行动的分子靶点、药物、患者总体生存率和治疗成本的信息:10年间,共有11 498名患者接受了精准肿瘤药物治疗。每年接受治疗的患者人数从 2013 年的 719 人增至 2023 年的 2873 人。开始治疗时的平均年龄为 63.62 岁(±12.83 岁),其中 57.66% 为男性。最常见的肿瘤是结直肠癌(40%)、非小细胞肺癌(33%)和黑色素瘤(12%)。确定的分子靶点包括 RAS(43%)、表皮生长因子受体(28%)、BRAF(17%)和 ALK(6%)。使用的主要药物包括西妥昔单抗(2791 例患者,24.27%)、帕尼单抗(1935 例患者,18.41%)和厄洛替尼(1312 例患者,11.41%)。平均总生存期为 20.7 个月(±23.78)个月,从 26.6 个月(±20.
{"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}
引用次数: 0
An overview of major depression disorder: The endocannabinoid system as a potential target for therapy 重度抑郁症概述:作为潜在治疗靶点的内源性大麻素系统。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-06 DOI: 10.1111/bcpt.14089
Sergio Zarazúa-Guzmán, Jorge Genaro Vicente-Martínez, Juan Manuel Pinos-Rodríguez, Jaime Iván Arevalo-Villalobos

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.

重度抑郁症是全球发病率最高的精神疾病,影响社会功能,降低生活质量。对该疾病病理生理学的部分了解、经济负担和较低的缓解率足以证明有理由对该主题进行更新,以寻找新的治疗方法和目标。内源性大麻素系统与抑郁症的发病有关,刺激或拮抗内源性大麻素系统是治疗重度抑郁症的一种很有前景的方法。近来,人们对大麻二酚(CBD)及其特性进行了广泛的研究;其镇痛、抗炎、抗肿瘤和神经保护作用甚至已在动物模型和临床试验中得到报道,并获准用于治疗某些神经退行性病变。CBD 在抑郁症生物模型和临床试验中的应用也不例外,在此,我们对比了当前 CBD 针对重度抑郁症病理机制的用药和药理学证据。
{"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}
引用次数: 0
Cytotoxicity, genotoxicity and mutagenicity of mixed ternary mononuclear Mg complex based on valproic acid with 1,10-phenanthroline in Saccharomyces cerevisiae and V79 cells 基于丙戊酸和 1,10-菲罗啉的混合三元单核镁复合物在酿酒酵母和 V79 细胞中的细胞毒性、遗传毒性和致突变性。
IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-04 DOI: 10.1111/bcpt.14091
Julia Vanini, Gabriel Berbigier Rodrigues, André Luiz Mendes Juchem, Temenouga Nikolova Guecheva, Sidnei Moura, Françoise Dumas, João Antonio Pêgas Henriques, Iuri Marques de Oliveira

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 Saccharomyces cerevisiae 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.

丙戊酸(VA)是一种广泛用于治疗影响中枢神经系统疾病的药物。由于其具有表观遗传调节潜力,人们一直在研究将其用于抗癌疗法的可能性。然而,VA 在应用中表现出不同的副作用。因此,与丙戊酸钠合成配位复合物可以产生具有减毒作用的新型活性药物。因此,我们研究了丙戊酸钠以及基于丙戊酸钠与 1,10-菲罗啉(Phen)配体的混合三元单核镁络合物 [Mg (Valp)2Phen] 在酿酒酵母和 V79 细胞中的遗传毒性和诱变潜力。在 V79 细胞中进行的 MTT 和克隆存活试验表明,镁复合物的细胞毒性高于丙戊酸钠。在酵母中也观察到类似的细胞毒性。这可能是由于[Mg(Valp)2Phen]具有插层能力,可诱导 DNA 链断裂,正如在彗星试验和微核试验中观察到的那样。从这个意义上说,[Mg(Valp)2Phen]诱导的 DNA 损伤修复需要 NER、HR、NHEJ 和 TLS 修复途径的成员。有趣的是,BER 蛋白显然增加了该药物的细胞毒性潜力。此外,与丙戊酸钠相比,[Mg(Valp)2Phen] 在 V79 细胞和酵母中显示出更高的细胞毒性,这表明它可用作细胞毒剂。
{"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)<sub>2</sub>Phen], 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)<sub>2</sub>Phen], 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)<sub>2</sub>Phen]. Interestingly, BER proteins apparently increase the cytotoxic potential of the drug. Furthermore, the [Mg(Valp)<sub>2</sub>Phen] 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}
引用次数: 0
期刊
Basic & Clinical Pharmacology & Toxicology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1