Fundamental & Clinical Pharmacology最新文献

{"title":"Impact of Direct Oral Anticoagulant Uptake on Hospitalizations for Stroke/Transient Ischemic Attack, Intracranial Hemorrhage, and Gastrointestinal Bleeding in Individuals With Atrial Fibrillation: A Population-Based Study","authors":"Tony Antoniou,&nbsp;Daniel McCormack,&nbsp;Tianru Wang,&nbsp;Mina Tadrous,&nbsp;Tara Gomes","doi":"10.1111/fcp.70051","DOIUrl":"10.1111/fcp.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Direct-acting oral anticoagulants (DOACs) have largely replaced warfarin for stroke prevention in patients with atrial fibrillation, yet their population-level impact on health outcomes and costs remains unclear. We examined whether the widespread uptake of DOACs was associated with changes in hospitalization rates and costs for stroke/transient ischemic attack (TIA), intracranial hemorrhage (ICH), and gastrointestinal bleeding among individuals with atrial fibrillation receiving publicly funded anticoagulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a population-based ecological time series study using administrative health data from Ontario, Canada, between 2003 and 2021. We used segmented negative binomial regression and generalized additive models to estimate immediate and post-DOAC uptake trends in hospitalization rates and costs following increased use of DOACs in 2012.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 12,134 hospitalizations for ICH, 59 946 for gastrointestinal bleeding, and 40 724 for stroke/TIA among anticoagulated individuals with atrial fibrillation. Following DOAC uptake, ICH rates (rate ratio [RR]: 0.88; 95% CI: 0.86–0.90) and costs (RR: 0.74; 95% CI: 0.62–0.88) declined immediately, with continued quarterly declines. Gastrointestinal bleeding rates increased initially (RR: 1.17; 95% CI: 1.14–1.20) and declined over time (RR per quarter: 0.99; 95% CI: 0.99–0.99). Gastrointestinal bleeding-related costs did not change significantly. Stroke/TIA rates remained stable, but hospitalization costs declined ($366 per 1000 individuals per quarter; 95% CI: −$562 to −$170).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>DOAC uptake was associated with reduced ICH rates and costs and an initial increase but subsequent decline in gastrointestinal bleeding rates. Despite stable stroke rates, reduced costs suggest potential long-term economic benefits. Our findings support the real-world effectiveness and safety of DOACs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244378","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 and Age Differences in Suspected Bleeding Reporting With Acetyl Salicylic Acid: A Descriptive Study in the Global Pharmacovigilance Database, Vigibase","authors":"Jean-Louis Montastruc,&nbsp;Alessandra Bura-Rivière","doi":"10.1111/fcp.70053","DOIUrl":"10.1111/fcp.70053","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The present study was performed to investigate putative sex differences in the reporting of acetyl salicylic acid (ASA)–related bleeding in the global pharmacovigilance database.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using Vigibase, the global pharmacovigilance database, all bleeding reports with ASA between January 1, 2008, and December 31, 2021, in adults were included. The main bleeding locations with ASA were compared in men versus women. A secondary objective was to analyze possible age differences. Results are presented as reporting odds ratios (RORs) with their 95% confidence interval.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 29 034 bleeding with ASA, the most frequent were gastrointestinal (41.2%), neurological (21.3%), and nasal (13.6%). Higher ROR values were found in men for all bleeding in general (ROR = 1.56 [1.51–1.61]) but also for gastrointestinal, neurological, nasal, and renal locations. Similar trends were found for “serious” reports (except for gastrointestinal bleeding). Neurological fatal reports were more frequently reported in men. These sex differences were also found in all the age categories. Higher ROR values were found in patients from 65 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The risk of total, “serious,” and fatal bleeding reporting with ASA was higher in men than in women and after 65 years. Similar conclusions can be made for the most frequent locations of ASA-associated bleeding: gastrointestinal followed by neurological and nasal ones.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244438","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":"Topical Probiotic Therapy Reduces Chemotherapy-Induced Oral Mucositis: Preclinical Evaluation in a Rat Model","authors":"Buse Kose Demirezen,&nbsp;Eren Demirpolat,&nbsp;Arzu Yay,&nbsp;Ozge Cengiz Mat,&nbsp;Mustafa Ermis","doi":"10.1111/fcp.70050","DOIUrl":"10.1111/fcp.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oral mucositis (OM) is a debilitating complication of chemotherapy and radiotherapy, characterized by painful ulcerations and inflammation of the oral mucosa. Current treatments provide limited efficacy and often lack regenerative properties. This study aimed to evaluate the therapeutic potential of topically administered probiotics in a rat model of OM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>OM was induced in Sprague–Dawley rats using 5-fluorouracil (5-FU) and acetic acid. Rats were randomized into groups receiving topical formulations of <i>Lactobacillus acidophilus</i>, <i>Lactobacillus reuteri</i>, <i>Bacillus clausii</i>, <i>Bacillus coagulans</i>, <i>Lactobacillus plantarum</i>, sucralfate, triamcinolone, and control. Treatments were applied for 5 consecutive days. OM severity was assessed using macroscopic and histopathological scoring, fibrosis grading, and inflammatory markers (TNF-α, IL-10, PGE₂).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>L. acidophilus</i> and <i>L. reuteri</i> significantly reduced macroscopic and histopathological OM scores compared to controls. <i>L. acidophilus</i> also demonstrated a notable reduction in fibrosis and PGE₂ levels (<i>p</i> &lt; 0.05), suggesting anti-inflammatory and antifibrotic activity. <i>B. clausii</i> and <i>B. coagulans</i> showed moderate efficacy, while sucralfate and triamcinolone reduced mucosal inflammation but were less effective in tissue regeneration. No significant changes in IL-10 were observed across groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Topically applied probiotics, particularly <i>L. acidophilus</i>, exhibit significant therapeutic potential in attenuating chemotherapy-induced OM by modulating inflammation and promoting mucosal healing. These findings support further exploration of localized probiotic therapies as a novel, non-systemic approach to manage OM in clinical settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232396","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":"Acute or Chronic β-Caryophyllene Systemic Administration in Healthy Adult Male Mice Does Not Modulate Anxiety-Like Extinction Behavior Induced by Subsequent Re-Exposure to 3D Maze","authors":"Rayan Fidel Martins Monteiro,&nbsp;Marcos Vinícius Lebrego Nascimento,&nbsp;Klinsmann Thiago Lima,&nbsp;Valdina Solimar Lopes Cardoso,&nbsp;José Ramon Gama Almeida,&nbsp;Wellington Junior Taisho Nagahama Costa,&nbsp;Anderson Valente-Amaral,&nbsp;Bruno Eduardo Godinho Teixeira,&nbsp;Ludmila Santos-Barbosa,&nbsp;Vinicius Teles Shirakura,&nbsp;Gilmara de Nazareth Tavares Bastos","doi":"10.1111/fcp.70049","DOIUrl":"https://doi.org/10.1111/fcp.70049","url":null,"abstract":"<p>Pharmacotherapy for major anxiety disorders continues to present dangerous side effects, complicating precise treatment choices for each patient. In this context, β-caryophyllene (BCP), a selective agonist of the cannabinoid type II receptor (CB2R), is recognized as a safe immunomodulatory drug. CB2R has recently been identified in glutamatergic and dopaminergic neurons, supporting its potential as a pharmacotherapy for mood disorders. Thus, we propose to investigate the effects of systemic BCP treatment (50, 100, and 200 mg/kg) on anxiety-like behavior. To this end, we utilized 92 adult male Swiss mice across two acute and one chronic pharmacological assay using the 3D maze test. In the acute assay, 30 min after treatment (BCP or vehicle), we conducted the One-Trial Protocol (OTP) lasting 12 min and the Two-Trial Protocol (TTP) lasting 12 min (comprising two trials of 5 min, with a 2-min interval between them). In the chronic assay, after 10 days of treatment (once daily; BCP or vehicle), testing was performed over five consecutive days (once daily; 12 min), 30 min after administration of BCP or vehicle. Additionally, locomotion was assessed. Under these conditions, we observed no effects on locomotion, anxiety-like behavior, or anxiety-like extinction behavior following either acute or chronic oral administration of BCP. Furthermore, we propose the use of TTP in the 3D maze as a valuable method for assessing acute pharmacological effects in mice. Lastly, behavioral modulation induced by CB2R agonists, particularly BCP, must be further investigated to better understand its potential neurological treatment applications and associated side effects.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146882","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":"Cholesterol Intake and Atorvastatin Modulate SCD1 and ELOVL6 in Rat Retroperitoneal Adipose Tissue","authors":"Jagoda Drag,&nbsp;Marek Szlosarczyk,&nbsp;Anna Gawedzka,&nbsp;Malgorzata Belczyk,&nbsp;Urszula Hubicka,&nbsp;Malgorzata Knapik-Czajka","doi":"10.1111/fcp.70048","DOIUrl":"10.1111/fcp.70048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Stearoyl-CoA desaturase 1 (SCD1) and elongase 6 (ELOVL6) are key enzymes in the synthesis of monounsaturated fatty acids (MUFA). Gene expression for SCD1 and ELOVL6 is high in the white adipose tissue (WAT) and is regulated at the transcriptional level by various factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to assess the effect of (a) cholesterol-enriched diet and (b) atorvastatin in a hypercholesterolemic state, on the relative mRNA and protein levels and indices for SCD1 and ELOVL6 in rat retroperitoneal WAT (rWAT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The mRNA and protein levels of SCD1 and ELOVL6 were determined using the RT-qPCR and Western blot techniques, respectively. Gas chromatography was used to determine the FA composition, and the SCD1 and ELOVL6 indices were then calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the HC group, the content of SAT decreased, as did the percentage of 14:0, 16:0, and 18:0. Conversely, PUFA content increased, as did the percentage of 18:2 n-6 and the indices for SCD18 and FA elongation compared to the CT group. In the AT group, the mRNA and protein levels of SCD1 increased, whereas the MUFA content and the percentage of 18:1 n-9 decreased compared to the HC group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study showed that a cholesterol-enriched diet increased the SCD1 index, leading to a decrease in SAT as these were used for MUFA synthesis. In contrast, atorvastatin lowered MUFA content, suggesting a protective effect of this compound in the rWAT of hypercholesterolemic rats. Furthermore, atorvastatin increased the expression of SCD1 mRNA and protein but did not affect the SCD1 index.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075143","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":"Nebivolol Mitigates the Pro-Oxidative and Pro-Inflammatory Effects of Cyclophosphamide in the Heart","authors":"Barbara M. Marchetti,&nbsp;Thales M. H. Dourado,&nbsp;Gustavo F. Pimenta,&nbsp;Alessandra O. Silva,&nbsp;Carlos R. Tirapelli","doi":"10.1111/fcp.70047","DOIUrl":"https://doi.org/10.1111/fcp.70047","url":null,"abstract":"<div>\u0000 \u0000 <p>Cyclophosphamide (CP) is an alkylating agent commonly used to treat malignant conditions. However, CP is associated with various adverse effects, one of which is cardiotoxicity. To minimize this toxicity, a common clinical strategy involves combining CP with a cytoprotective agent. One of the main causes of cardiac toxicity from CP is redox imbalance. Nebivolol, an antihypertensive medication that selectively targets β₁-adrenoceptors, has demonstrated cardioprotective effects in certain situations, partly due to its antioxidant properties. In this study, we evaluated whether nebivolol could reduce the harmful effects of CP on the heart. Male C57BL/6 mice were treated with nebivolol (10 mg/kg/day, administered by gavage for 5 days) and subsequently injected with either saline or a single dose of CP (300 mg/kg, via intraperitoneal injection). We assessed pro-oxidative and pro-inflammatory parameters in the left ventricle 24 h after the CP injection. Treatment with CP resulted in increased levels of superoxide (O₂^•−) derived from NADPH-oxidase, upregulation of NOX1 expression, and elevated hydrogen peroxide (H₂O₂) levels and lipoperoxidation. Pretreatment with nebivolol significantly mitigated these pro-oxidative effects. Moreover, nebivolol prevented the increase in COX2 expression induced by CP. Echocardiographic analyses indicated that, despite the molecular changes caused by CP, cardiac function was preserved in the CP-injected mice. In conclusion, nebivolol demonstrates cardioprotective effects against the toxicity of CP by reducing pro-oxidative and pro-inflammatory responses. Thus, nebivolol may represent a novel clinical approach for managing the cardiotoxic effects associated with CP.</p>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038050","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":"Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies","authors":"Dominique Mesquita e Silva,&nbsp;Laís de Souza Lacerda,&nbsp;Andrea de Souza Andrioli,&nbsp;Wilson Rodrigues Braz,&nbsp;Lara Melo Campos,&nbsp;Mayara Rodrigues Brandão de Paiva,&nbsp;Frederico Pittella,&nbsp;Rodrigo Luiz Fabri,&nbsp;Guilherme Diniz Tavares","doi":"10.1111/fcp.70046","DOIUrl":"10.1111/fcp.70046","url":null,"abstract":"<p>This review highlights the integration of drug repurposing and nanotechnology-driven delivery strategies as innovative approaches to enhance the antifungal activity of statins against mucosal candidiasis, providing a framework for future translational research and clinical application. The rising prevalence of antifungal resistance and virulence factors of <i>Candida albicans</i> underscore the limitations of current therapies. Statins, commonly used as lipid-lowering agents, have emerged as attractive repurposed drug candidates due to their ability to interfere with fungal ergosterol biosynthesis and Ras-mediated signaling pathways. However, repurposed statins face major translational barriers, including poor water solubility, limited mucosal bioavailability, and dose-dependent systemic toxicity. Nanotechnology-driven delivery platforms offer versatile solutions to these challenges, enabling site-directed delivery, improved stability, enhanced permeability, and controlled release. Lipid and polymeric nanocarriers, particularly chitosan-based nanoparticles, enable controlled release and prolonged mucosal retention, making them suitable for localized antifungal therapy. This review explores the integration of statin repurposing with advanced drug delivery strategies as a novel therapeutic paradigm for mucosal candidiasis. Updated evidence demonstrating the antifungal potential of nano-formulated statins is summarized, in conjunction with a general overview of design aspects relevant to optimizing delivery systems. Although still in early stages of investigation, this synergistic approach holds promise for overcoming resistance mechanisms and reducing the recurrence rates associated with existing antifungals. Ultimately, leveraging drug repurposing alongside nanotechnology may accelerate the translation of statin-based antifungal therapies into clinical practice, providing an innovative and cost-effective avenue to broaden the therapeutic arsenal against mucosal <i>Candida</i> infections.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033140","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":"No Impact of Vancomycin MIC, AUC, or AUC/MIC in Enterococcus faecium Bacteremia","authors":"Anne Limelette,&nbsp;Thibaut Tromeur,&nbsp;Rami Rhaiem,&nbsp;Morgane Bonnet,&nbsp;Yohan N'Guyen","doi":"10.1111/fcp.70039","DOIUrl":"https://doi.org/10.1111/fcp.70039","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There is no clear pharmacokinetic and pharmacodynamic (PK/PD) target during vancomycin-susceptible <i>Enterococcus faecium</i> bacteremia (EFB).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To investigate whether in-hospital mortality was associated with susceptibility to amoxicillin or vancomycin minimum inhibitory concentration (MIC) of the strain and with area under the curve over 24 h (AUC) and AUC/MIC during EFBs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>All <i>E. faecium</i> strains isolated from blood cultures performed between January 1, 2017, and December 31, 2022, were included, and clinicobiological data were retrospectively extracted from corresponding medical records. The Vancomycin MICs were estimated using the VITEK 2 automated system. AUC was calculated among patients who received vancomycin during their first episode of EFB with available data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two hundred fifteen <i>E. faecium</i> strains not susceptible to amoxicillin had been isolated in 207 patients (125 male, median age 69 [1–98] years) with biliary and digestive tract diseases, hematologic malignancies, or COVID-19 in 124 (59.9%), 35 (16.9%), and 17 (8.2%) cases, respectively. The median vancomycin MIC was 0.5 [0.5–2] mg/L, and 67 patients (32.3%) died during the hospitalization. In-hospital mortality was not associated with susceptibility to amoxicillin (<i>p</i> = 0.14) or vancomycin MIC (<i>p</i> = 0.07) of the strain. Neither mean AUC (592.7 versus 521.7mgh/L) nor mean AUC/MIC ratio (1066.5 versus 1000.5) was associated with in-hospital mortality (<i>p</i> = 0.17 and <i>p</i> = 0.54, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Besides amoxicillin susceptibility and vancomycin MIC of the strain, there was no significant association between in-hospital mortality and vancomycin AUC or AUC/MIC. Retrospective observational studies focusing on in-hospital mortality among patients with severe comorbidities may not be adequate for the determination of the PK/PD target of vancomycin.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832378","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":"Leveraging Fiber Photometry to Decipher Neural Circuits Underlying Anxiety in Mice","authors":"Salma R. Abdennebi,&nbsp;Nour El Haya Touihri,&nbsp;Emmanuelle Corruble,&nbsp;Denis J. David,&nbsp;Indira Mendez-David","doi":"10.1111/fcp.70043","DOIUrl":"https://doi.org/10.1111/fcp.70043","url":null,"abstract":"<p>Anxiety disorders rank among the most prevalent mental health conditions worldwide, significantly affecting patients' lives. They are frequently comorbid with other psychiatric disorders, often exacerbating their severity. Current pharmacological treatments; selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines, remain limited in efficacy and are associated with undesirable side effects, underscoring the urgent need for alternative therapeutic approaches. However, progress in developing new treatments has been hindered by an incomplete understanding of the neural mechanisms underlying these disorders. Bridging this knowledge gap requires advanced research tools capable of providing deeper insight into the neural circuits involved in anxiety. Fiber photometry (FP) has emerged as a powerful and cost-effective technique for measuring neural activity in freely moving animal models. By enabling real-time monitoring of calcium dynamics in specific neural populations within defined brain regions, this method offers invaluable insights into both normal physiological processes and pathological states. In this review, we first present an accessible introduction to FP, detailing its apparatus, procedures, and key advantages and limitations. We then conducted a comprehensive analysis of 39 studies indexed in PubMed that have employed FP to investigate neural circuits implicated in anxiety. Our review reveals the techniques' significant contributions across different research domains, including physiological (33%), pathological (53%), and dual-purpose studies (13%). Beyond summarizing its utility, our goal is to make FP more accessible to researchers. By providing a foundational guide for its integration into future scientific projects, we aim to facilitate advances in anxiety research and contribute to the development of novel therapeutic strategies.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814655","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":"Repurposing Asparaginase Therapy to Target Cisplatin-Resistant Cancer Cells","authors":"Jiantao Wang,&nbsp;Nasim Pouryaghoub,&nbsp;Robert Strauss,&nbsp;Jiri Bartek,&nbsp;Si Min Zhang,&nbsp;Sean G. Rudd","doi":"10.1111/fcp.70044","DOIUrl":"https://doi.org/10.1111/fcp.70044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cisplatin and its derivatives remain a cornerstone in the treatment of solid malignancies. Resistance is a major factor limiting their clinical utility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>In the present study, we set out to interrogate therapeutic approaches to target cisplatin-resistant cancer cells. We focused on therapies exploiting metabolic pathways that are altered in drug-resistant cells. We sought to find an existing therapy that has monotherapy efficacy against cisplatin-resistant cancer cells that can also re-sensitize to cisplatin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used lung and ovarian cancer cell lines with acquired resistance to cisplatin together with drug sensitivity assays, conducted both with monotherapies and cisplatin combinations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We show that cancer cell lines with acquired resistance to cisplatin have altered levels of enzymes involved in glutamine metabolism, which can result in differential sensitivity to targeted agents. We show that expression of one of these enzymes—the glutamate-cystine antiporter SLC7A11, up-regulated 6-fold in a cisplatin-resistant lung cancer cell line—has potential prognostic significance in lung cancer but not ovarian cancer. After identifying a common dependency of cisplatin-resistant cancer cells upon extracellular glutamine, we then evaluate the utility of the long-standing anti-leukemic therapy asparaginase (ASNase)—which possesses both asparaginase and glutaminase activity—as a potential approach. We show ASNase preferentially inhibits the proliferation of cisplatin-resistant cancer cells and can potentially re-sensitize these cells to cisplatin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results underpin the prevalence of altered metabolism in cisplatin-resistant cells and highlight the potential utility of re-purposing ASNase to target these cells, warranting further investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811256","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}