Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"The Feasibility and Acceptability of a Collaborative Deprescribing Intervention to Reduce Anticholinergic Burden Among Hospitalised Older Patients","authors":"Kinda Ibrahim,&nbsp;Eloise Radcliffe,&nbsp;Edward Hewertson,&nbsp;Andrew Bates,&nbsp;Andy Fox,&nbsp;Emily Smith,&nbsp;Cathrine Mckenzie,&nbsp;Liam Jones,&nbsp;Sara Mckelvie,&nbsp;Ngianga Ii Kandala,&nbsp;Sara McCloskey,&nbsp;Tracey Sach,&nbsp;Stephen Lim","doi":"10.1111/bcpt.70277","DOIUrl":"10.1111/bcpt.70277","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>37%–48% of older patients receive anticholinergic medicines, increasing the risk for falls, delirium, dementia and death. Hospital admission may provide an opportunity for deprescribing to improve outcomes. This study evaluated the feasibility and acceptability of a digital tool to identify anticholinergic medicines and support deprescribing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A pre-post feasibility study was conducted (May–September 2025). Patients aged ≥ 75 with an ACB score of ≥ 3, screened using a digital tool, were recruited. The identified medications were highlighted to the clinical team to prompt a medication review (stop, reduce or switch). Primary outcomes were recruitment and retention. Secondary outcomes included medication and patients’ outcomes, healthcare use and acceptability from qualitative interviews.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Recruitment was challenging; 65 out of 301 patients with ACB ≥ 3 (22%) were eligible, 21 participated, of which 15 (80%) completed follow-up. Mean age was 84.7 years, and intervention costs were £9.33 per patient. Interviews indicated technical and organisational challenges. Mean ACB scores were 3.85 (admission), 3.45 (discharge), 3.0 (1 month) and 3.44 (3 months), with slight changes in cognition and delirium but no changes in depressive symptoms or quality of life.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although acceptable, recruitment and technical challenges limited feasibility. Findings should be interpreted cautiously due to the small sample size, and further refinement is needed before implementation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808223","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":"Low-Dose Fisetin Supplementation and Its Association With Chronic Inflammation in Middle-Aged and Older Adults: Study Protocol for a Triple-Blind, Randomised, Placebo-Controlled Trial","authors":"Juliette Tavenier,&nbsp;Magnus Berglind,&nbsp;Line Fleischer Hach,&nbsp;Louise Westberg Strejby Christensen,&nbsp;Maria Jana Masarikova,&nbsp;Rafal Yahya,&nbsp;Mette Bendtz Lindstrøm,&nbsp;Baker Nawfal Jawad,&nbsp;Anna Zatkova,&nbsp;Rikke Lundsgaard Nielsen,&nbsp;Helle Gybel Juul-Larsen,&nbsp;Thomas Kallemose,&nbsp;Jan Olof Nehlin,&nbsp;Morten Baltzer Houlind,&nbsp;Ove Andersen,&nbsp;Line Jee Hartmann Rasmussen","doi":"10.1111/bcpt.70290","DOIUrl":"10.1111/bcpt.70290","url":null,"abstract":"<p>Systemic chronic inflammation contributes to the development of many age-related chronic diseases and represents a promising target for interventions aiming at promoting healthy aging. Fisetin is a naturally occurring flavonoid with anti-inflammatory, antioxidant and senolytic effects in vitro and in animal models, but evidence from randomised controlled trials in humans is limited. This study is a triple-blind, randomised, placebo-controlled trial designed to investigate the association between daily fisetin supplementation and changes in plasma soluble urokinase plasminogen activator receptor (suPAR) levels, as well as the occurrence and severity of adverse events, in generally healthy middle-aged and older adults, with exploratory evaluation of additional biomarkers and functional outcomes. Participants aged ≥ 50 will be randomised to receive 100 mg of oral fisetin or placebo once daily for 7 weeks. The primary outcome is the between-group difference in the change in plasma levels of suPAR from Baseline to Week 7. The secondary outcome is the between-group difference in the occurrence and severity of adverse events during the study period. In addition, exploratory outcomes will evaluate the association of fisetin supplementation with other soluble and cellular biomarkers of inflammation, aging and cellular senescence, as well as measures of frailty, physical and cognitive function and subjective health.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808247","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":"Neuroprotective Effects of Senecio brasiliensis Extract Against Chlorpyrifos-Induced Neurotoxicity and Oxidative Stress in Drosophila melanogaster","authors":"Maria Vitória Takemura Mariano,&nbsp;Giany Gabriely Padão dos Santos,&nbsp;Ana Beatriz Guedes de Souza,&nbsp;Thaís de Camargo Neves,&nbsp;Franklin Vinny Medina Nunes,&nbsp;Pedro Henrique Vicenzi,&nbsp;Karen Kich Gomes,&nbsp;Mauro Eugênio Medina Nunes,&nbsp;Marcelo Farina,&nbsp;Jeferson Luis Franco,&nbsp;Thaís Posser","doi":"10.1111/bcpt.70288","DOIUrl":"10.1111/bcpt.70288","url":null,"abstract":"<p>Chlorpyrifos (CP) is an organophosphate insecticide that induces neurotoxicity through acetylcholinesterase (AChE) inhibition and redox imbalance, raising environmental and occupational health concerns. Plant-derived compounds from <i>Senecio brasiliensis</i>, native to the Pampa biome, offer multitarget therapeutic potential. This study evaluated the protective effects of the hydroalcoholic extract of <i>S. brasiliensis</i> (HESB) against CP-induced toxicity in <i>Drosophila melanogaster</i> (Harwich strain). Adult females (3–5 days old) were exposed for 48 h to control (1% sucrose), CP (0.25 ppm), HESB (1 mg/mL) or CP + HESB. CP increased mortality (37.3% ± 6.6%; <i>p</i> &lt; 0.001) and impaired locomotion in the negative geotaxis (17.2 ± 3.0 s; <i>p</i> &lt; 0.001) and footbridge (52.2 ± 5.2 s) assays, decreased AChE, GST and CAT activity (−31.8%, −45.8% and −72.3%, respectively; <i>p</i> = 0.006, 0.025 and 0.006), elevated ROS (+97.0%; <i>p</i> = 0.007), nitrite (+13.1%; <i>p</i> = 0.006) and TBARS (+25.6%; <i>p</i> = 0.010), depleted NPSH (−29.2%; <i>p</i> = 0.003) and PSH (−35.9%; <i>p</i> = 0.013) and reduced cell viability (−17.9%; <i>p</i> = 0.013). HESB co-treatment attenuated all CP-induced alterations, bringing parameters to control-comparable values (<i>p</i> &gt; 0.05). These findings indicate that HESB exerts neuroprotective effects against CP toxicity through modulation of cholinergic function, attenuation of oxidative and nitrosative stress and preservation of thiol homeostasis.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808311","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":"Acute Kidney Injury During Vancomycin Treatment in Adult Patients With Haematologic Malignancies: A Multicentre Retrospective Study","authors":"Yuzhu Wang,&nbsp;Jie Li,&nbsp;Xingyun Hou,&nbsp;Ying Zhang,&nbsp;Chengchun Zuo,&nbsp;Xiaoqiang Ding,&nbsp;Xiaoyu Li,&nbsp;Qianzhou Lv,&nbsp;Hejin Lai,&nbsp;Kunming Pan","doi":"10.1111/bcpt.70297","DOIUrl":"10.1111/bcpt.70297","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acute kidney injury (AKI) during vancomycin treatment remains a rare occurrence in adult patients with haematological malignancies (HMs). The objective of this multicentre study was to investigate the incidence and risk factors for AKI during vancomycin treatment in patients with HM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The present study examined patients who were admitted to hospital and receiving vancomycin therapy between 2009 and 2024 at three tertiary hospitals. The primary outcome was the incidence of AKI during vancomycin treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study comprised a total of 610 out of 982 patients. The incidence of AKI during vancomycin treatment among patients with HM was 13.0% (79/610). Multiple logistic regression analysis revealed that cardiac insufficiency (OR 3.305, 95% CI = 1.498–7.290, <i>p</i> = 0.003), chronic kidney disease (OR 5.074, 95% CI = 1.636–15.735, <i>p</i> = 0.005), hypoalbuminaemia (OR 2.930, 95% CI = 1.515–5.664, <i>p</i> = 0.001), concomitant spironolactone (OR 3.362, 95% CI = 1.586–7.290, <i>p</i> = 0.002) and chemotherapeutic drugs (OR 6.683, 95% CI = 2.025–22.051, <i>p</i> = 0.002) were independent risk factors for AKI during vancomycin treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The occurrence of AKI in adult patients with HM during vancomycin treatment is a prevalent issue and is associated with a number of clinical and treatment-related factors. HM patients with cardiac dysfunction, chronic kidney disease, hypoalbuminaemia or concomitant spironolactone, chemotherapeutic agents may have a higher risk of AKI during vancomycin treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808227","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":"Poisoning With Toxic Alcohols in Denmark","authors":"Thomas Jacobsen,&nbsp;Anja Julie Huusom,&nbsp;Tonny Studsgaard Petersen,&nbsp;Stinna Skaaby,&nbsp;Paula Edeusa Cristina Hammer","doi":"10.1111/bcpt.70291","DOIUrl":"https://doi.org/10.1111/bcpt.70291","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Poisoning with ethylene glycol and methanol remains a recurrent problem in Scandinavia. This study aimed to describe the epidemiology, exposure circumstances, clinical characteristics and management of toxic alcohol poisonings reported to the Danish Poison Information Centre to support preventive initiatives and improve toxicological counselling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>All calls concerning confirmed or suspected ingestion of ethylene glycol or methanol registered by the Danish Poison Information Centre between 2006 and 2022 were reviewed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 592 exposures involving ethylene glycol (85%) or methanol were identified. Children accounted for 25% of exposures and adults for 61%, with a predominance of males (73%). Accidental ingestion accounted for 71% of exposures. In more than 60% of cases, the Danish Poison Information Centre assessed a risk of moderate to potentially fatal poisoning. Hospitalization was recommended in approximately 70% of cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Ethylene glycol poisoning was more common than methanol poisoning and was primarily associated with accidental ingestion of engine coolant products following inappropriate storage or handling. Many patients were referred for hospital evaluation because risk assessment relied mainly on circumstantial information suggesting potential severe poisoning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Toxic alcohol poisoning in Denmark is primarily caused by accidental ethylene glycol ingestion. Rapid blood analysis of toxic alcohols may reduce delayed treatment and unnecessary hospitalization.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785036","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":"CCL19 and CCL21 Display Reciprocal Dependence on R209 in ECL2 of CCR7 for Receptor Activation, Relating to Differences in the Chemokine N-Terminal Region","authors":"Mette Marie Rosenkilde,&nbsp;Brian F. Volkman,&nbsp;Francis C. Peterson,&nbsp;Christopher T. Veldkamp,&nbsp;Gertrud Malene Hjortø","doi":"10.1111/bcpt.70289","DOIUrl":"https://doi.org/10.1111/bcpt.70289","url":null,"abstract":"<p>CCL19 and CCL21 interact differentially with their shared receptor CCR7. A key amino acid important for CCL19-mediated receptor activation is arginine 209 (R209) in extracellular loop 2 (ECL2) of CCR7. CCL21 activation of CCR7, in contrast, does not depend on R209. Using chimeric versions of CCL19 and CCL21, we investigate the importance of the N-terminal region, core domain and C-terminal region of CCL19 and CCL21 in contributing to this distinction. Overall, signalling via G_αi and β-arrestin2 recruitment induced by CCL19 and all variants containing the N-terminal region of CCL19 is negatively impacted by substituting arginine 209 with an alanine (R209A), whereas signalling induced by ligands with the N-terminal region of CCL21 is either unaffected or positively affected by this substitution. Of interest, the R209A substitution greatly improves the ability of CCL21 and all chemokine variants carrying the N-terminal region of CCL21 to induce β-arrestin2 recruitment by CCR7, with a general two-fold increase in efficacy at 100-nM chemokine concentrations. Our data fit with the proposed model for CCL19 and CCL21 docking at CCR7, where the more negatively charged N-terminus of CCL19 contacts R209 during insertion into the CCR7 binding pocket, while CCL21 contacts the binding pocket in a different manner.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784991","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":"Genotype-Dependent Effects of Mechanical Stretch and GATA4-Targeted Compound 3i-1262 in Cardiomyopathy Patient–Derived hiPSC-Cardiomyocytes","authors":"Saana Pohjavaara,&nbsp;Sini M. Kinnunen,&nbsp;Heikki Ruskoaho,&nbsp;Katriina Aalto-Setälä,&nbsp;Mika J. Välimäki,&nbsp;Virpi Talman","doi":"10.1111/bcpt.70284","DOIUrl":"https://doi.org/10.1111/bcpt.70284","url":null,"abstract":"<p>Genetic hypertrophic and dilated cardiomyopathies (HCM and DCM, respectively) are characterised by structural and functional abnormalities that can lead to heart failure. However, current therapies mainly reduce symptoms. Patient-derived human induced pluripotent stem cell (hiPSC)–derived cardiomyocytes provide a valuable platform to study genotype-specific pathophysiology and pharmacology. We subjected hiPSC-cardiomyocytes from healthy individuals and from patients carrying pathogenic <i>MYBPC3</i> (HCM) or <i>LMNA</i> (DCM) mutations to cyclic mechanical stretch, with or without the GATA4-targeted anti-hypertrophic compound 3i-1262, and assessed hypertrophy-associated, mechanosensitive and metabolism-related genes by qPCR, and hypertrophy-related proteins by Western blotting. Compared to control, HCM cardiomyocytes displayed higher basal expression of <i>NPPB</i> and <i>MYH7</i>, whereas DCM cardiomyocytes exhibited lower basal expression of <i>NPPB</i> and <i>NPPA</i>. Mechanical stretching induced <i>NPPB</i> and <i>MYH7</i> upregulation in control cardiomyocytes, delayed <i>MYH7</i> upregulation in HCM cardiomyocytes and <i>NPPA</i> downregulation in DCM cardiomyocytes. Other mechanosensitive genes, such as <i>GAL</i>, <i>CSRP3</i> and <i>SLC16A9</i>, also exhibited genotype- and time-dependent regulation. In control cardiomyocytes, 3i-1262 produced limited modulation of stretch-induced gene expression but showed little or no effect in patient-derived cardiomyocytes. These findings demonstrate that cardiomyopathy mutations influence gene and protein expression, responses to mechanical stretch and 3i-1262, underscoring the value of patient-derived hiPSC-cardiomyocytes in disease modelling and drug discovery.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784867","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":"Discrepancies in Vancomycin Clearance Estimation Among Renal Function Models in Patients With Low Serum Creatinine Levels: A Pilot Study","authors":"Yuki Nakano,&nbsp;Toshinori Hirai,&nbsp;Rintaro Sogawa,&nbsp;Hirotsugu Hasuwa,&nbsp;Chisato Shimanoe","doi":"10.1111/bcpt.70287","DOIUrl":"https://doi.org/10.1111/bcpt.70287","url":null,"abstract":"<div>\u0000 \u0000 <p>Vancomycin dosing is guided by population pharmacokinetic models that consider renal function. However, low serum creatinine (Scr) levels may reflect heterogeneous conditions and lead to inaccurate vancomycin clearance. This study evaluated the predictive ability of different population pharmacokinetic models for vancomycin clearance in low Scr settings. This single-centre retrospective study included hospitalised patients aged ≥18 years who received intravenous vancomycin. Predicted vancomycin clearance was calculated using population pharmacokinetic models across six scenarios incorporating creatinine clearance (Ccr), serum albumin, reduced muscle mass, Scr rounding and Japanese cystatin C–based estimated glomerular filtration rate (eGFR_{Japanese, Cys-C}). Agreement was evaluated using concordance correlation coefficients (CCC) and Bland–Altman analysis. Among the six scenarios (<i>n</i> = 24), the Ccr-based model exhibited the best agreement (CCC = 0.79). Models based on eGFR_{Japanese, Cys-C} or rounded-up Scr systematically underestimated clearance under augmented renal clearance. In those with a body mass index ≥25 kg/m², clearance increased more substantially, and a similar trend was observed in patients aged &lt;70 years. In patients with low Scr, Ccr-based models showed better agreement with two-point estimated vancomycin clearance. In obese or younger patients with low Scr, two-point estimated vancomycin clearance may be a practical approach for vancomycin dosing.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784084","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":"Long-Term Persistence and Treatment Changes of Antihypertensive Therapy: A 5-Year Cohort Study","authors":"Amal Asiri,&nbsp;Sumaira Mubarik,&nbsp;Jens H. J. Bos,&nbsp;Catharina C. M. Schuiling-Veninga,&nbsp;Eelko Hak,&nbsp;Katja Taxis","doi":"10.1111/bcpt.70286","DOIUrl":"https://doi.org/10.1111/bcpt.70286","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To estimate persistence with antihypertensive therapy (AHT) and describe treatment changes and associated factors among persistent patients over 5 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a longitudinal cohort study using the IADB.nl pharmacy database in the Netherlands, including adults who initiated AHT between 2014 and 2018 after a 2-year washout. Persistence was assessed annually using a ±45-day window around each treatment anniversary. Among patients persistent throughout follow-up, treatment changes were classified yearly as no change, switching, intensification or de-intensification. A Markov model estimated transitions between treatment states, and logistic regression evaluated baseline factors associated with treatment changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 22 027 starters (mean age 58.1 years, 51.1% women), annual persistence declined from 88.8% in year 1 to 80.7% in year 5, with 52.7% remaining persistent over 5 years. Treatment changes were most frequent in the first year, when 53.5% of persistent patients underwent intensification, de-intensification, or switching, and declined thereafter. The probability of remaining in the same state was high, particularly for ‘no change’ state (0.86). Female sex, combination therapy initiation and initiating on beta-blockers or calcium-channel blockers were associated with treatment changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Antihypertensive pharmacotherapy is frequently modified early after initiation, followed by increasing long-term treatment stability among persistent users.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753810","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":"Sex-Specific Relationships Between Nociceptin/Orphanin FQ Peptide (NOP) Receptors and Alcohol Drinking: Longitudinal PET Studies in Cynomolgus Monkeys","authors":"Paul W. Czoty,&nbsp;Kiran K. Solingapuram Sai,&nbsp;Mack D. Miller,&nbsp;Michael D. Moore,&nbsp;Paul J. Myburgh,&nbsp;Laura R. Grace,&nbsp;Joshua N. Prete,&nbsp;Phillip M. Epperly","doi":"10.1111/bcpt.70282","DOIUrl":"10.1111/bcpt.70282","url":null,"abstract":"<div>\u0000 \u0000 <p>Drugs that interact with brain nociceptin/orphanin FQ (NOP) receptors can decrease ethanol consumption in preclinical models of alcohol use disorder (AUD). Studies using positron emission tomography (PET imaging) in humans with AUD reported lower levels of NOP receptors compared to controls. Here, uptake of the NOP receptor–selective PET radiotracer [¹¹C]NOP-1A was measured in monkeys (six males, five females) when ethanol-naïve and again after a 4-month induction procedure plus 6 months of ethanol drinking (22 h/day, 5 days/week). Although there were no sex differences in brain uptake of [¹¹C]NOP-1A before ethanol self-administration, sex differences were observed in relationships between [¹¹C]NOP-1A uptake and ethanol-related measures. Baseline [¹¹C]NOP-1A uptake in the orbitofrontal cortex in males and caudate nucleus in females predicted future ethanol intakes. Moreover, chronic ethanol self-administration produced changes in [¹¹C]NOP-1A uptake in AUD-related brain areas. Increases in uptake were observed in the putamen of both sexes and in the nucleus accumbens and amygdala of males; females showed a decrease in the insula. Changes in [¹¹C]NOP-1A uptake in the orbitofrontal cortex, putamen and hypothalamus of males and caudate nucleus of females were related to ethanol intake. These results demonstrate bidirectional relationships between brain NOP receptors and ethanol self-administration and provide evidence of subtle sex differences in these interactions.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719805","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}