Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Targeting AVEN Liquid-Liquid Phase Separation in Colorectal Cancer: Insights From a Raddeanin A-Based Chemical Probe","authors":"Xichao Yu,&nbsp;Hui Wu,&nbsp;Kezhen Guo,&nbsp;Zihao Liu,&nbsp;Lianxin Zhou,&nbsp;Hongjie Wu,&nbsp;Shuyuan Wang,&nbsp;Jiaqi Fu,&nbsp;Xing Cui,&nbsp;Zhifei Fu,&nbsp;Mengjie Guo,&nbsp;Ye Yang","doi":"10.1111/bcpt.70257","DOIUrl":"10.1111/bcpt.70257","url":null,"abstract":"<div>\u0000 \u0000 <p>Mitochondrial dysfunction is a pivotal pathogenic mechanism in colorectal cancer (CRC), which is further exacerbated by dysregulated liquid–liquid phase separation (LLPS). However, the mechanisms underlying mitochondrial dysfunction and LLPS, as well as their therapeutic targeting, remain unclear. Using Raddeanin A as a probe and through multiomics analysis, we identified apoptosis and caspase activation inhibitor (AVEN) as a potential therapeutic target. AVEN was significantly upregulated in CRC tissues and localized near mitochondria-endoplasmic reticulum contact sites (MERCS). Biophysical assays confirmed that AVEN undergoes LLPS via its intrinsically disordered regions (IDRs). Critically, we found that AVEN IDRs orchestrate mitochondrial homeostasis through dual LLPS-dependent mechanisms: inhibiting apoptosis and facilitating post-damage mitochondrial transfer. Furthermore, we identified sumatriptan (SUM) as a potent inhibitor of AVEN IDRs, which demonstrated promising therapeutic efficacy in mouse models and clinical cohorts. Our study highlights the critical role of AVEN in regulating mitochondrial homeostasis via LLPS and suggests that targeting AVEN represents a promising therapeutic strategy for CRC.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148222812","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":"The Imperative of Involving Nurses When Reviewing Psychiatric Medication: a Qualitative Study of Implementing Physician-Led Medication Reviews for Psychiatric Outpatients With Diabetes","authors":"Johan Frederik Mebus Meyer Christensen,&nbsp;Elisabeth Mebus Meyer Christensen,&nbsp;Ulla Christensen,&nbsp;Signe Düring,&nbsp;Gesche Jürgens","doi":"10.1111/bcpt.70259","DOIUrl":"10.1111/bcpt.70259","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>We previously found that implementing medication reviews by a physician specialised in clinical pharmacology at interdisciplinary conferences with prescribing physicians and nurses led to a relative reduction in the number of drugs and potentially inappropriate prescriptions (PIPs) in psychiatric outpatients with diabetes. Adhering to the framework of health technology assessments (HTAs) and to facilitate direct implementation, we subsequently demonstrated the intervention as cost neutral.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to identify contextual, organisational and interprofessional barriers and facilitators in implementing the intervention focusing on nurses' role at interdisciplinary conferences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted semi-structured interviews with available staff and four patients from the intervention group. We conducted a primary thematic analysis with HTA as a framework, while a secondary analysis situated the themes into a contextual understanding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Interdisciplinary dialogue tailors pharmacological recommendations to patients adhering to clinical pragmatism rather than generic prescription guidelines. It enables professional growth and reciprocal learning and levels out an inherent doctor–nurse hierarchy. However, when conferences were online or hybrid, nurses did not benefit to the same extent and had the feeling of being set aside.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Interdisciplinary medication reviews in psychiatry may improve the clinical relevance of pharmacological decision-making and level out an inherent physician–nurse hierarchy in psychiatry.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148222827","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":"Effects of Celecoxib and Etoricoxib on the Pharmacokinetics and Pharmacological Effects of Orally Administered Tramadol: A Randomised Controlled Trial","authors":"Tuukka Saarikoski,&nbsp;Teijo I. Saari,&nbsp;Janne T. Backman,&nbsp;Mikko Niemi,&nbsp;Pertti J. Neuvonen,&nbsp;Klaus T. Olkkola,&nbsp;Kari Laine","doi":"10.1111/bcpt.70261","DOIUrl":"10.1111/bcpt.70261","url":null,"abstract":"<p>Tramadol is a widely used analgesic whose bioactivation to O-desmethyltramadol is primarily mediated by cytochrome P450 2D6 (CYP2D6). Genetic variability and drug–drug interactions affecting CYP2D6 may influence tramadol pharmacokinetics and pharmacological effects. Cyclooxygenase-2 inhibitors are frequently co-administered with tramadol in multimodal analgesia, but their potential to affect tramadol disposition and effects remains incompletely characterised. Celecoxib has been reported to act as a weak inhibitor of CYP2D6 in vivo. This randomised, single-blind, placebo-controlled crossover study evaluated the effects of 8-day pretreatment with celecoxib or etoricoxib (200 and 120 mg once daily, respectively), compared with placebo, on the pharmacokinetics and pharmacological effects of a single 100 mg oral dose of tramadol in 12 healthy volunteers. Plasma concentrations of tramadol and O-desmethyltramadol were measured, and pharmacological effects were assessed using visual analogue scales, psychomotor testing (digit symbol substitution test) and cold pressor pain models. Celecoxib pretreatment did not change tramadol exposure but reduced the formation of O-desmethyltramadol, decreasing the geometric mean AUC ratio (GMR) of O-desmethyltramadol to tramadol (AUC_m/AUC_p) by 24% relative to placebo (90% CI, 0.69–0.84; <i>p</i> &lt; 0.001). Etoricoxib had minimal effects on tramadol exposure or metabolism (GMR 0.92; 90% CI, 0.84–1.02; <i>p</i> = 0.13). In conclusion, celecoxib modestly inhibited the bioactivation of tramadol, but not etoricoxib. Differences in pharmacological effects were negligible.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70261","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216284","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":"Detection of Anti-Infliximab and Anti-Adalimumab Antibodies Below Manufacture's Threshold in a TDM Cohort Using Signal-to-Noise Ratio","authors":"Lise Pedersen","doi":"10.1111/bcpt.70258","DOIUrl":"10.1111/bcpt.70258","url":null,"abstract":"&lt;p&gt;Therapeutic drug monitoring (TDM) of anti-drug antibodies (ADA) and drug concentrations is used to optimize tumour necrosis factor-α inhibitor therapy [&lt;span&gt;1&lt;/span&gt;]. The development of ADA against infliximab or adalimumab increases the risk of reduced clinical response and infusion reactions [&lt;span&gt;2&lt;/span&gt;]. When ADA accelerates drug clearance resulting in undetectable drug levels, patients risk a secondary loss of response to treatment necessitating a treatment change [&lt;span&gt;3&lt;/span&gt;]. Appropriate positivity thresholds of ADA representing drug clearance are therefore critical. Manufacturers of ADA assays provide default positivity thresholds, derived under controlled experimental conditions using drug-naïve samples [&lt;span&gt;4&lt;/span&gt;], that may not reflect real-world TDM samples originating from patients who have already been exposed to the drug and may contain circulating drug, ADA, or both. Consequently, manufacturer-defined thresholds may not be optimal for clinical TDM. The lack of standardization of ADA assay provides a further challenge, leading to inconsistent immunogenicity reporting across studies. Using the WHO reference panels for ADA in method validation is a step towards harmonizing ADA assays [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Recently, Nice et al. showed the benefits of validating and lowering the positivity thresholds for a commercial ADA assay thereby obtaining a better detection of clinically meaningful anti-adalimumab [&lt;span&gt;6&lt;/span&gt;]. At Holbaek Hospital, infliximab and adalimumab drug levels and corresponding ADA have been measured in paired samples using commercial enzyme-linked immunosorbent (ELISA) assays as part of a TDM service since 2019. In the TDM samples with undetectable drug concentrations and ADA classified as ‘negative’ using the manufacturer default positivity threshold, optical density (OD) values more than 2–3 times above the OD value of the negative control were sometimes observed.&lt;/p&gt;&lt;p&gt;The ADA signal-to-noise (S/N) ratio, a continuous measure, has been proposed as an alternative and more sensitive means of characterizing ADA responses [&lt;span&gt;7, 8&lt;/span&gt;]. In this study, S/N ratios were calculated from all ADA OD values obtained between 2019 and 2025 to explore the use of S/N as a supplementary measure to detect low-titre ADA. Validation of the S/N ratio included determination of limit of detection, precision and linearity of the S/N response using the WHO standards available for infliximab and adalimumab ADA.&lt;/p&gt;&lt;p&gt;Serum concentrations of infliximab and adalimumab and anti-infliximab/adalimumab were quantified using ELISA kits from Promonitor (Grifols Diagnostic Solutions Inc., 10 808 Willow Ct., San Diego, CA 92127, USA) according to the manufacturer's instructions. Infliximab (Reference: 5060230000) and Promonitor adalimumab (Reference: 5080230000) ELISA kits followed a 1:200 sample dilution. Absence of drug is defined as &lt; 0.2 mg/L and &lt; 0.3 mg/L for infliximab and adalimumab, respectively. Anti-inflixim","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203900","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":"Correction to “6-Nitrodopamine Potentiates Catecholamine-Induced Ca2+i Release in Human Aortic Smooth Muscle and Modulates Vascular Smooth Muscle Contractility”","authors":"","doi":"10.1111/bcpt.70263","DOIUrl":"10.1111/bcpt.70263","url":null,"abstract":"<p>\u0000 <span>J. Britto-Júnior</span>, <span>A. T. Lima</span>, <span>S. Qiao</span>, et al., “ <span>6-Nitrodopamine Potentiates Catecholamine-Induced Ca²⁺_i Release in Human Aortic Smooth Muscle and Modulates Vascular Smooth Muscle Contractility</span>,” <i>Basic &amp; Clinical Pharmacology &amp; Toxicology</i> <span>138</span>, no. <span>4</span> (<span>2026</span>): e70224, https://doi.org/10.1111/bcpt.70224.\u0000 </p><p>The article title “6-Nitrodopamine Potentiates Catecholamine-Induced Ca²⁺_i Release in Human Aortic Smooth Muscle and Modulates Vascular Smooth Muscle Contractility” was missing one word. This should have read “6-Nitrodopamine Potentiates Catecholamine-Induced Ca²⁺_i Release in Human Aortic Smooth Muscle Cells and Modulates Vascular Smooth Muscle Contractility”.</p><p>The online version of this article has been corrected accordingly.</p><p>We apologize for this error.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161540","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":"Efficacy and Safety of the Traditional Chinese Medicine Yunnan Baiyao in the Treatment of Diabetic Foot Ulcers: a Multicentre, Randomised Clinical Trial","authors":"Ying Zhang,&nbsp;Jinghui Zhao,&nbsp;Ershun Huang,&nbsp;Yunfeng Li,&nbsp;Xiankun Yin,&nbsp;Jun Zhang,&nbsp;Yanming Lin,&nbsp;Hua Zhang,&nbsp;Chunlei Zhang,&nbsp;Lu Tie,&nbsp;Wenhui Wang,&nbsp;Long Zhang","doi":"10.1111/bcpt.70253","DOIUrl":"10.1111/bcpt.70253","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetic foot ulcers (DFUs) constitute an increasing clinical challenge, driven by the escalating prevalence of diabetes and the paucity of effective therapies. This multicentre, randomised, open-label, blinded-endpoint trial investigated the efficacy and safety of Yunnan Baiyao (YNBY), a traditional Chinese medicine, as an adjunctive therapy for DFUs. Patients with DFUs (Wagner Grade 3 or 4) from three hospitals were randomised 2:2:1 to YNBY powder, YNBY ointment and control groups, all receiving standard of care. A total of 117 patients completed the trial. The 2-week percentage of wound area reduction (PWAR) was significantly higher in YNBY powder (61.5%) and YNBY ointment (70.0%) groups than that in the control group (46.4%, <i>p</i> &lt; 0.01). The 1-week PWAR was almost doubled in the YNBY powder group (36.1%) and the YNBY ointment group (42.9%) relative to the control group (19.5%, <i>p</i> &lt; 0.05). The percentage of complete healing within 8 weeks (control group, 25.0%; powder group, 54.2%; ointment group, 61.9%) did not reach statistical significance. No significant differences were observed between the YNBY powder and ointment groups. The adjunctive use of YNBY powder or ointment with standard therapy significantly accelerates wound closure. This effective, inexpensive, easy-to-apply traditional medicine can serve as an effective adjunct to standard DFUs care.</p>\u0000 <p><b>Trial registration:</b> https://clinicaltrials.gov/, NCT06197412 (Registration Date: 12/17/2023)</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155137","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":"Astragaloside IV Ameliorates Allergic Rhinitis Comorbid With Asthma by Inhibiting the Antigen-Presenting Function of B Cells","authors":"Ruizhi Wang,&nbsp;Junhai Chen,&nbsp;Fan Ye,&nbsp;Yiwen Li,&nbsp;Tianzhu Chen,&nbsp;Min Dai,&nbsp;Kun Zhang,&nbsp;Qintai Yang,&nbsp;Min Zhou","doi":"10.1111/bcpt.70247","DOIUrl":"10.1111/bcpt.70247","url":null,"abstract":"<div>\u0000 \u0000 <p>Astragaloside IV (AST) is one of the main active components of <i>Astragalus membranaceus</i> (Fisch.) Bunge, possessing definite immunomodulatory properties. However, its efficacy and mechanism remain unclear in allergic rhinitis comorbid with asthma (ARCA). This study aims to investigate whether AST can improve ARCA by inhibiting antigen presentation. An ARCA mouse model was established to assess airway allergic symptoms; serum inflammatory factors were detected by ELISA, airway tissue pathology by HE, PAS and Masson staining and inflammatory factor expression, antigen-presenting cell activation and JAK2/STAT1 pathway activity by WB, IHC and IF. AST improved airway allergic symptoms, downregulated the expression of OVA-sIgE and IL-4 and upregulated the expression of OVA-sIgG. It also alleviated eosinophil infiltration, goblet cell metaplasia and collagen fibre proliferation and inhibited the expression of ECP, CD3e, CD4 and IL-4 in airway tissues. The antigen-presenting function of B cells in the airway tissues of ARCA mice was activated, while AST inhibited this function. Moreover, AST downregulated the expression of p-JAK2, STAT1, p-STAT1 and MHC II in airway tissues. In conclusion, B cells are the key effector cells mediating antigen presentation in the challenge phase of ARCA. AST can inhibit the antigen-presenting function of B cells via regulating the JAK2/STAT1 signalling pathway, thereby alleviating the Th2-type inflammatory response in ARCA.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148363","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":"Quantifying the Impact of Discrepancies Between Actual and Recorded Blood Sampling Times on Bayesian Forecasting for Area Under the Concentration–Time Curve Estimation of Vancomycin","authors":"Tomoyuki Yamada,&nbsp;Kazutaka Oda,&nbsp;Yoko Hiyama,&nbsp;Takashi Ueda,&nbsp;Hirokazu Furusho,&nbsp;Tomomi Katanoda,&nbsp;Takashi Tomita,&nbsp;Hiroaki Matsuo,&nbsp;Takeshi Ide,&nbsp;Sachiko Jingami,&nbsp;Yusuke Kusaka,&nbsp;Hirofumi Jono","doi":"10.1111/bcpt.70254","DOIUrl":"10.1111/bcpt.70254","url":null,"abstract":"<div>\u0000 \u0000 <p>The effect of discrepancies in sampling time on the accuracy of area under the concentration–time curve (AUC) estimation remains unclear. We evaluated how discrepancies between actual and recorded blood sampling times impact vancomycin AUC estimation using one-point (trough) and two-point (trough and peak) strategies in critically ill patients. In total, 25 patients at five Japanese hospitals were enrolled; 21 underwent sampling on Day 1 (AUC_day1) and 14 on Days 3–5 (AUC_ss). Reference AUCs were calculated using trapezoidal methods. Bayesian forecasting estimated AUCs from one- or two-point sampling. Systematic trough (≤ 4 h earlier) and peak (−1 to +4 h) time discrepancies were introduced. Predictive performance was defined as estimated/reference AUC ratios within an acceptable range of 0.9–1.1. For AUC_day1, two-point sampling was more robust to trough discrepancies than one-point sampling (acceptable interquartile range [IQR] up to 105 vs. 30 min) but highly sensitive to peak timing (acceptable IQR −20 and +10 min). For AUC_ss, similar trends were observed. Overall, two-point sampling offers superior robustness against trough discrepancies. However, because peak sampling is highly sensitive to timing errors, if the exact peak sampling time cannot be verified, clinicians may consider remeasuring the concentration or switching to one-point trough sampling.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155141","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":"Prescribing Patterns in Fatal Intoxications Involving Zopiclone and Alprazolam: An Observational Register-Based Study","authors":"Lova Tralla,&nbsp;Sara Gustavsson,&nbsp;Carl Söderberg,&nbsp;Anna K. Jönsson,&nbsp;Fredrik C. Kugelberg","doi":"10.1111/bcpt.70256","DOIUrl":"10.1111/bcpt.70256","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Zopiclone was recently identified as a frequent contributor to fatal drug-intoxications in Sweden. However, characteristics of misuse and factors associated with prescribed use remain insufficiently described. Alprazolam has a more established misuse profile.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of the study was to describe and compare characteristics of fatal intoxications positive for zopiclone or alprazolam, focusing on prescription status and factors associated with prescribed drug use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fatal intoxications between 2012 and 2020 with zopiclone and/or alprazolam in blood were identified using the Swedish Cause of Death Register and the Swedish forensic medicine database. Prescriptions within 1 year before death, and health and sociodemographic data were obtained from national registers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1270 zopiclone cases, 84% were prescribed users compared to 22% of 1532 alprazolam cases. For both substances, prescribed use was associated with female sex (zopiclone: aOR = 1.68, 95% CI = 1.22–2.30; alprazolam: aOR = 2.04, 95% CI = 1.54–2.71), suicide relative to accidental intoxication (zopiclone: aOR = 1.61, 95% CI = 1.11–2.33; alprazolam: aOR = 3.21, 95% CI = 2.16–4.75) and age ≥ 46 years (zopiclone: aOR = 2.26, 95% CI = 1.45–3.54; alprazolam: aOR = 3.20, 95% CI = 2.29–4.46). Psychiatry-contact and previous self-harm were associated with prescribed zopiclone use, but not alprazolam.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Fatal intoxications involving zopiclone differ from alprazolam. While factors associated with prescribed use were often shared, substance-specific preventative strategies could be beneficial.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155130","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":"Toxicity Test of Total Particulate Matter in Mainstream Cigarette Smoke Based on Lung-Hepatocyte Vascularised Microfluidic Chip.","authors":"Rui Li, Su Zhou, Gang Li, Minyang Gu, Dan Gao, Liming Tang, Da Wu, Zhen Feng","doi":"10.1111/bcpt.70238","DOIUrl":"10.1111/bcpt.70238","url":null,"abstract":"<p><p>Microfluidic chips have relatively short test cycles, and their ability to reproduce tissue structure, environment and function with a certain degree of complexity greatly improves the accuracy of toxicity test models. In this study, a vascularised microfluidic chip containing lung-hepatocytes was constructed to test the toxicity of total particulate matter (TPM) in mainstream cigarette smoke. After exposure to TPM for 3 consecutive days, there was a significant increase in LDH release from chip cells, significant changes in the MUC5AC and ZO-1 proteins of Calu-3 and a significant increase in the relative expression level of the CYP1A1 gene of HepG2 in a dose-dependent manner. These results indicate that TPM can penetrate through Calu-3 cultured at the air-liquid interface in the upper chamber of the chip and HUVEC in the middle chamber, affecting HepG2 in the lower chamber. This reflects the entire in vivo exposure process of TPM under 3D conditions. The chip constructed in this study can assess key toxicological endpoints of TPM. It not only simulates the primary pulmonary response to TPM but also captures the subsequent hepatic metabolic activation. This provides a more comprehensive and physiologically relevant toxicity assessment and offers a new method for TPM toxicity testing.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 6","pages":"e70238"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947253","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}