S. Arraki Zava, F. Maizaud, H. Sayadi, Y. Fromage, P. Marquet, J. B. Woillard, C. Monchaud
In lifelong immunosuppressive therapy, missed doses of prolonged-release tacrolimus are almost inevitable and may reduce drug exposure, compromising transplant outcomes. Using pharmacokinetic models, we simulated delayed and missed doses in virtual kidney and liver transplant recipients. Our simulations showed that a missed dose significantly lowers exposure, with recovery taking 2–4 days. For delays shorter than 12 h, the full dose should be taken immediately; for delays between 12 and 24 h, half the dose should be administered; for a missed dose, 150% should be given at the next intake. These strategies may help maintain therapeutic exposure and preserve transplant outcomes.
{"title":"Managing Delayed or Missed Doses of Prolonged-Release Tacrolimus in Transplant Recipients: Implications for Drug Exposure and Recovery Strategies","authors":"S. Arraki Zava, F. Maizaud, H. Sayadi, Y. Fromage, P. Marquet, J. B. Woillard, C. Monchaud","doi":"10.1111/bcpt.70157","DOIUrl":"https://doi.org/10.1111/bcpt.70157","url":null,"abstract":"<p>In lifelong immunosuppressive therapy, missed doses of prolonged-release tacrolimus are almost inevitable and may reduce drug exposure, compromising transplant outcomes. Using pharmacokinetic models, we simulated delayed and missed doses in virtual kidney and liver transplant recipients. Our simulations showed that a missed dose significantly lowers exposure, with recovery taking 2–4 days. For delays shorter than 12 h, the full dose should be taken immediately; for delays between 12 and 24 h, half the dose should be administered; for a missed dose, 150% should be given at the next intake. These strategies may help maintain therapeutic exposure and preserve transplant outcomes.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659547","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":"Retrospective Analysis of the Use of Oral Ivermectin and 5% Permethrin Cream in Galicia (Spain)","authors":"S. Vazquez-Prieto, A. Vaamonde, E. Paniagua","doi":"10.1111/bcpt.70152","DOIUrl":"https://doi.org/10.1111/bcpt.70152","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659512","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}
Epigallocatechin-3-gallate (EGCG) is a polyphenolic compound with strong antioxidant properties and is abundantly found in green tea. We investigated how EGCG affects the liver injury of high-dose paracetamol in this study. In our study, 56 rats were divided into seven groups (n = 8): healthy control, EGCG (100 mg/kg), paracetamol (2 g/kg), paracetamol + EGCG 25 (2 g/kg + 25 mg/kg), paracetamol + EGCG 50 (2 g/kg + 50 mg/kg), paracetamol + EGCG 100 (2 g/kg + 100 mg/kg) and paracetamol + N-acetyl cysteine (NAC, 2 g/kg + 140 mg/kg). Our findings suggest that high-dose paracetamol induces liver injury through endoplasmic reticulum (ER) stress and that EGCG alleviates liver injury by attenuating ER stress-induced inflammasome signalling.
Romana Santos Gama, Luiz Carlos Passos, Welma Wildes Amorim, Renato Morais Souza, Marcio Galvão Oliveira
This study aimed to evaluate the effectiveness of pharmacist-led medication reviews in reducing the anticholinergic burden of hospitalised patients with cardiovascular diseases (CVDs), to identify which anticholinergic medications were most frequently prescribed or discontinued during hospitalisation and to investigate factors associated with an elevated anticholinergic burden via secondary analysis of the INFAR study. An uncontrolled before-and-after design was used, and medication reviews were performed for all patients so that the anticholinergic burden of medications prescribed to older adults during their hospital stay could be examined. The mean age of the 319 patients was 68.9 years (±6.2), and upon hospital admission, 40.4% were classified as having a high anticholinergic burden, decreasing to 22.6% at discharge. Multivariate analysis at admission indicated that polypharmacy (PR = 2.00; 95% CI = 1.47–2.72) and potentially inappropriate medication (PR = 4.47; 95% CI = 2.10–9.53) were independently associated with a higher anticholinergic burden; however, only inappropriate medication was significantly associated with a high burden (PR = 2.39; 95% CI = 1.54–3.71) at discharge. The results indicate that a clinical pharmacist-led medication review may reduce the anticholinergic burden in older adults with CVD, highlighting the importance of such a review in promoting safer prescribing practices during hospitalisation.
本研究旨在评估药师主导的药物评价在减少心血管疾病（cvd）住院患者抗胆碱能负担方面的有效性，确定住院期间最常开具或停药的抗胆碱能药物，并通过对INFAR研究的二次分析调查与抗胆碱能负担升高相关的因素。采用不受控制的前后对照设计，并对所有患者进行药物评价，以便检查老年人住院期间处方的抗胆碱能药物负担。319例患者的平均年龄为68.9岁（±6.2岁），入院时40.4%的患者被归为抗胆碱能负荷高，出院时降至22.6%。入院时的多因素分析显示，多药（PR = 2.00, 95% CI = 1.47-2.72）和可能不适当的用药（PR = 4.47, 95% CI = 2.10-9.53）与较高的抗胆碱能负担独立相关；然而，只有用药不当与出院时的高负担显著相关（PR = 2.39; 95% CI = 1.54-3.71）。结果表明，临床药师主导的药物审查可能会减少老年心血管疾病患者的抗胆碱能负担，强调了这种审查在促进住院期间更安全的处方实践中的重要性。
{"title":"Reducing Anticholinergic Burden in Hospitalised Older Adults: Analysis From the INFAR Study","authors":"Romana Santos Gama, Luiz Carlos Passos, Welma Wildes Amorim, Renato Morais Souza, Marcio Galvão Oliveira","doi":"10.1111/bcpt.70160","DOIUrl":"10.1111/bcpt.70160","url":null,"abstract":"<p>This study aimed to evaluate the effectiveness of pharmacist-led medication reviews in reducing the anticholinergic burden of hospitalised patients with cardiovascular diseases (CVDs), to identify which anticholinergic medications were most frequently prescribed or discontinued during hospitalisation and to investigate factors associated with an elevated anticholinergic burden via secondary analysis of the INFAR study. An uncontrolled before-and-after design was used, and medication reviews were performed for all patients so that the anticholinergic burden of medications prescribed to older adults during their hospital stay could be examined. The mean age of the 319 patients was 68.9 years (±6.2), and upon hospital admission, 40.4% were classified as having a high anticholinergic burden, decreasing to 22.6% at discharge. Multivariate analysis at admission indicated that polypharmacy (PR = 2.00; 95% CI = 1.47–2.72) and potentially inappropriate medication (PR = 4.47; 95% CI = 2.10–9.53) were independently associated with a higher anticholinergic burden; however, only inappropriate medication was significantly associated with a high burden (PR = 2.39; 95% CI = 1.54–3.71) at discharge. The results indicate that a clinical pharmacist-led medication review may reduce the anticholinergic burden in older adults with CVD, highlighting the importance of such a review in promoting safer prescribing practices during hospitalisation.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676194","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}
Gadolinium-based contrast agents, widely used in magnetic resonance imaging, raise safety concerns due to their potential cytotoxic and genotoxic effects, especially at high doses or repeated exposures. In this study, the cytogenotoxic potential of gadoteric acid in NIH3T3 fibroblast cells was evaluated using in vitro and in silico approaches. NIH3T3 cells were treated with increasing concentrations of gadoteric acid. Cytotoxicity was evaluated by MTS assay and genotoxicity by comet assay; hydrogen peroxide (75 μM) was used as a positive control. In addition, the interaction of gadoteric acid with DNA topoisomerase IIα, DNA topoisomerase IIβ, DNA polymerase β, and B-DNA was examined by molecular docking. MTS assay results showed a dose-dependent decrease in cell viability with an IC50 of 28.19 mM. Comet assay revealed significant DNA damage only at the highest concentration (56.38 mM) (p < 0.05), which also caused marked cytotoxicity. Thus, the observed DNA damage likely resulted from cytotoxicity stress rather than direct strand breaks. In silico docking predicted a high binding affinity of gadoteric acid for DNA polymerase β (−11.7 kcal/mol) and other DNA-related targets. However, these predictions require experimental validation. Overall, gadoteric acid exhibited dose-dependent cytotoxicity and limited genotoxicity at high concentrations, suggesting that DNA damage occurs secondary to cytotoxic effects rather than a direct genotoxic mechanism.
{"title":"Gadoteric Acid Induces Dose-Dependent DNA Damage and Enzyme Binding in Fibroblast Cells","authors":"İbrahim Halil Kenger","doi":"10.1111/bcpt.70150","DOIUrl":"https://doi.org/10.1111/bcpt.70150","url":null,"abstract":"<div>\u0000 \u0000 <p>Gadolinium-based contrast agents, widely used in magnetic resonance imaging, raise safety concerns due to their potential cytotoxic and genotoxic effects, especially at high doses or repeated exposures. In this study, the cytogenotoxic potential of gadoteric acid in NIH3T3 fibroblast cells was evaluated using in vitro and in silico approaches. NIH3T3 cells were treated with increasing concentrations of gadoteric acid. Cytotoxicity was evaluated by MTS assay and genotoxicity by comet assay; hydrogen peroxide (75 μM) was used as a positive control. In addition, the interaction of gadoteric acid with DNA topoisomerase IIα, DNA topoisomerase IIβ, DNA polymerase β, and B-DNA was examined by molecular docking. MTS assay results showed a dose-dependent decrease in cell viability with an IC<sub>50</sub> of 28.19 mM. Comet assay revealed significant DNA damage only at the highest concentration (56.38 mM) (<i>p</i> < 0.05), which also caused marked cytotoxicity. Thus, the observed DNA damage likely resulted from cytotoxicity stress rather than direct strand breaks. In silico docking predicted a high binding affinity of gadoteric acid for DNA polymerase β (−11.7 kcal/mol) and other DNA-related targets. However, these predictions require experimental validation. Overall, gadoteric acid exhibited dose-dependent cytotoxicity and limited genotoxicity at high concentrations, suggesting that DNA damage occurs secondary to cytotoxic effects rather than a direct genotoxic mechanism.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659545","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}
Ahmed I. Soliman, Jean Wactawski-Wende, Amy E. Millen, Kathleen M. Hovey, Michael J. LaMonte
Aims
Examine the association between proton pump inhibitor (PPI) use and plasma levels of four biomarkers of haemostasis: fibrinogen, von Willebrand factor (vWF), high-sensitivity CRP (hs-CRP) and plasminogen activator inhibitor-1 (PAI-1) in postmenopausal women.
Methods
We conducted a cross-sectional analysis on 200 women in the Buffalo Osteoporosis and Periodontitis study Year 17 visit. PPI use was assessed using medication inventories, and biomarkers were measured using frozen plasma samples. Linear regression was used to estimate mean differences for each biomarker according to PPI use (yes/no) and duration (≤ 1 year, > 1 year). Logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for having a high versus low level of each biomarker. Models were adjusted for major cardiovascular risk factors to account for potential confounding.
Results
PPI users had non-statistically significant higher levels of vWF (mean difference = 52.9 mIU/mL, p = 0.38) and log hs-CRP (mean difference = 0.1 mg/L, p = 0.5) compared to non-users. PPI users for > 1 year had non-statistically significant higher odds of having a high level of vWF (OR = 1.08, 95% CI: 0.51–2.31) and hs-CRP (OR = 1.16, 95% CI: 0.58–2.33) compared to non-users.
Conclusions
There was no significant association between PPI use and measured plasma haemostatic markers.
{"title":"Proton Pump Inhibitors and Biomarkers of Haemostasis in Postmenopausal Women: The Buffalo OsteoPerio Study","authors":"Ahmed I. Soliman, Jean Wactawski-Wende, Amy E. Millen, Kathleen M. Hovey, Michael J. LaMonte","doi":"10.1111/bcpt.70156","DOIUrl":"https://doi.org/10.1111/bcpt.70156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Examine the association between proton pump inhibitor (PPI) use and plasma levels of four biomarkers of haemostasis: fibrinogen, von Willebrand factor (vWF), high-sensitivity CRP (hs-CRP) and plasminogen activator inhibitor-1 (PAI-1) in postmenopausal women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a cross-sectional analysis on 200 women in the Buffalo Osteoporosis and Periodontitis study Year 17 visit. PPI use was assessed using medication inventories, and biomarkers were measured using frozen plasma samples. Linear regression was used to estimate mean differences for each biomarker according to PPI use (yes/no) and duration (≤ 1 year, > 1 year). Logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for having a high versus low level of each biomarker. Models were adjusted for major cardiovascular risk factors to account for potential confounding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PPI users had non-statistically significant higher levels of vWF (mean difference = 52.9 mIU/mL, <i>p</i> = 0.38) and log hs-CRP (mean difference = 0.1 mg/L, <i>p</i> = 0.5) compared to non-users. PPI users for > 1 year had non-statistically significant higher odds of having a high level of vWF (OR = 1.08, 95% CI: 0.51–2.31) and hs-CRP (OR = 1.16, 95% CI: 0.58–2.33) compared to non-users.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>There was no significant association between PPI use and measured plasma haemostatic markers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659546","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}
Vasospasm of arterial grafts remains a critical problem in coronary artery bypass grafting (CABG), contributing to perioperative ischemia and graft failure. This study evaluates the antispastic effects of combining the ROCK inhibitor fasudil and isosorbide dinitrate (ISDN) on the human internal mammary artery (IMA).
Methods
IMA rings (n = 208) from 94 CABG patients were investigated in a myograph. Relaxation to fasudil (−3.5 log M), ISDN (−4 log M) and their combination (FI solution) was assessed after precontraction with potassium chloride (KCl 30 mM) or U46619 (10−8 M). The preventive effects of FI solution on the contraction induced by KCl or U46619 were studied. ROCK2 protein and cGMP levels were measured using Western blot and ELISA.
Results
FI solution demonstrated superior relaxation compared to either drug alone against KCl or U46619 (p < 0.001). Pretreatment with FI inhibited the contraction by KCl and U46619, significantly higher than that with either drug alone (p < 0.0001). FI also reduced ROCK2 expression (p = 0.0001) and elevated cGMP levels (p = 0.0002).
Conclusions
The combination of fasudil and ISDN effectively prevents and relieves IMA vasospasm mediated by both voltage-operated and receptor-operated calcium channels, with a long-lasting vasorelaxing effect. The FI solution offers a novel approach for preventing and relieving IMA spasm in CABG.
{"title":"Significant Antispastic Effect of Combined Fasudil and Isosorbide Dinitrate on Internal Mammary Artery in Coronary Artery Bypass Grafting","authors":"You-Feng Zhang, Hai-Tao Hou, Qin Yang, Guo-Wei He","doi":"10.1111/bcpt.70148","DOIUrl":"https://doi.org/10.1111/bcpt.70148","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Vasospasm of arterial grafts remains a critical problem in coronary artery bypass grafting (CABG), contributing to perioperative ischemia and graft failure. This study evaluates the antispastic effects of combining the ROCK inhibitor fasudil and isosorbide dinitrate (ISDN) on the human internal mammary artery (IMA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>IMA rings (<i>n</i> = 208) from 94 CABG patients were investigated in a myograph. Relaxation to fasudil (−3.5 log M), ISDN (−4 log M) and their combination (FI solution) was assessed after precontraction with potassium chloride (KCl 30 mM) or U46619 (10<sup>−8</sup> M). The preventive effects of FI solution on the contraction induced by KCl or U46619 were studied. ROCK2 protein and cGMP levels were measured using Western blot and ELISA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>FI solution demonstrated superior relaxation compared to either drug alone against KCl or U46619 (<i>p</i> < 0.001). Pretreatment with FI inhibited the contraction by KCl and U46619, significantly higher than that with either drug alone (<i>p</i> < 0.0001). FI also reduced ROCK2 expression (<i>p</i> = 0.0001) and elevated cGMP levels (<i>p</i> = 0.0002).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The combination of fasudil and ISDN effectively prevents and relieves IMA vasospasm mediated by both voltage-operated and receptor-operated calcium channels, with a long-lasting vasorelaxing effect. The FI solution offers a novel approach for preventing and relieving IMA spasm in CABG.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"138 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659680","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}
Ragnhild Bergene Skråstad, Øyvind Salvesen, Trine Naalsund Andreassen, Trond Oskar Aamo, Kristian Hveem, Steinar Krokstad, Olav Spigset
Background
Phosphatidylethanol 16:0/18:1 (PEth) is a widely used alcohol marker, but how sex, body size and composition and kidney function affect the dose–response relationship between alcohol consumption and PEth is not fully understood.
Objective
The aim of the study was to investigate whether sex, age, body size and composition and kidney function influence the estimate of alcohol consumed at a given PEth concentration.
Methods
This is a longitudinal population-based cohort study including 24 902 participants from the Trøndelag Health Study (HUNT4). Associations were assessed using a regression model.
Findings
When analysed together, sex and soft lean mass were statistically significant independent predictors of alcohol consumption at a given PEth concentration. To achieve the same PEth concentration as a female, a male with identical body composition could on average consume 21% more alcohol, according to our model. Independent of sex, a person with 10% higher soft lean mass could consume 3.9% more alcohol to achieve the same PEth concentration. When soft lean mass was excluded, height and body weight became significant predictors.
Conclusions
Sex, body composition and body size may have an impact on the dose–response relationship between alcohol consumption and PEth concentration. Thus, these factors will contribute to the uncertainty when estimating ethanol intake from a given PEth concentration.
{"title":"Impact of Sex, Age, Body Composition and Kidney Function on the Relationship Between Self-Reported Alcohol Consumption and Phosphatidylethanol—Data From the HUNT Study","authors":"Ragnhild Bergene Skråstad, Øyvind Salvesen, Trine Naalsund Andreassen, Trond Oskar Aamo, Kristian Hveem, Steinar Krokstad, Olav Spigset","doi":"10.1111/bcpt.70141","DOIUrl":"10.1111/bcpt.70141","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Phosphatidylethanol 16:0/18:1 (PEth) is a widely used alcohol marker, but how sex, body size and composition and kidney function affect the dose–response relationship between alcohol consumption and PEth is not fully understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of the study was to investigate whether sex, age, body size and composition and kidney function influence the estimate of alcohol consumed at a given PEth concentration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a longitudinal population-based cohort study including 24 902 participants from the Trøndelag Health Study (HUNT4). Associations were assessed using a regression model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>When analysed together, sex and soft lean mass were statistically significant independent predictors of alcohol consumption at a given PEth concentration. To achieve the same PEth concentration as a female, a male with identical body composition could on average consume 21% more alcohol, according to our model. Independent of sex, a person with 10% higher soft lean mass could consume 3.9% more alcohol to achieve the same PEth concentration. When soft lean mass was excluded, height and body weight became significant predictors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Sex, body composition and body size may have an impact on the dose–response relationship between alcohol consumption and PEth concentration. Thus, these factors will contribute to the uncertainty when estimating ethanol intake from a given PEth concentration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12669429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653347","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}
Adnan Taan Al Khafaji, Ali Mohammed Barakat, Akram Jooda Al Zaidy, Ali Adnan Taan, Raed Fanoukh Aboqader Al-Aouadi
Cardiovascular diseases (CVDs) remain a leading global cause of mortality, necessitating novel therapeutic strategies to address myocardial injury, adverse remodelling and impaired cardiomyocyte regeneration. Exosomes, nanoscale extracellular vesicles secreted by nearly all cell types, have emerged as pivotal mediators of intercellular communication, influencing cardiac physiology and pathology through their cargo of nucleic acids, proteins and lipids. These vesicles participate actively in processes such as cytoprotection, angiogenesis, apoptosis regulation and immune modulation, which are critical for cardiac repair and regeneration. Recent preclinical and clinical studies highlight the promising regenerative capabilities of exosomes, especially those derived from stem cells and immune cells, positioning them as innovative therapeutic tools and diagnostic biomarkers in CVD management. Despite their potential advantages over traditional cell therapies, including lower immunogenicity and enhanced targeting, several hurdles remain before exosomes can be routinely applied in clinical practice. Challenges include the lack of standardized isolation and characterization protocols, heterogeneity of exosome populations, inefficient cargo loading methods, off-target biodistribution and safety concerns related to immune response and infectious risk. Ongoing research aims to overcome these obstacles to realize exosomes' full potential in cardiovascular regenerative medicine, with diagnostic applications currently representing a nearer-term goal.
{"title":"Exosomes in Cardiovascular Disease: Emerging Roles, Therapeutic Potential and Translational Challenges","authors":"Adnan Taan Al Khafaji, Ali Mohammed Barakat, Akram Jooda Al Zaidy, Ali Adnan Taan, Raed Fanoukh Aboqader Al-Aouadi","doi":"10.1111/bcpt.70151","DOIUrl":"10.1111/bcpt.70151","url":null,"abstract":"<p>Cardiovascular diseases (CVDs) remain a leading global cause of mortality, necessitating novel therapeutic strategies to address myocardial injury, adverse remodelling and impaired cardiomyocyte regeneration. Exosomes, nanoscale extracellular vesicles secreted by nearly all cell types, have emerged as pivotal mediators of intercellular communication, influencing cardiac physiology and pathology through their cargo of nucleic acids, proteins and lipids. These vesicles participate actively in processes such as cytoprotection, angiogenesis, apoptosis regulation and immune modulation, which are critical for cardiac repair and regeneration. Recent preclinical and clinical studies highlight the promising regenerative capabilities of exosomes, especially those derived from stem cells and immune cells, positioning them as innovative therapeutic tools and diagnostic biomarkers in CVD management. Despite their potential advantages over traditional cell therapies, including lower immunogenicity and enhanced targeting, several hurdles remain before exosomes can be routinely applied in clinical practice. Challenges include the lack of standardized isolation and characterization protocols, heterogeneity of exosome populations, inefficient cargo loading methods, off-target biodistribution and safety concerns related to immune response and infectious risk. Ongoing research aims to overcome these obstacles to realize exosomes' full potential in cardiovascular regenerative medicine, with diagnostic applications currently representing a nearer-term goal.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145628257","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}
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