Canadian journal of physiology and pharmacology最新文献_第4页

Validation and predictive performance of a physiologically based single dose pharmacokinetic model of mirtazapine for elderly and pediatric populations. 老年人和儿童米氮平单剂量生理药代动力学模型的验证和预测性能。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0054

Yanhao Liu, Ying Wang, Huan Zhou, Feng Ding

{"title":"Validation and predictive performance of a physiologically based single dose pharmacokinetic model of mirtazapine for elderly and pediatric populations.","authors":"Yanhao Liu, Ying Wang, Huan Zhou, Feng Ding","doi":"10.1139/cjpp-2026-0054","DOIUrl":"https://doi.org/10.1139/cjpp-2026-0054","url":null,"abstract":"This study reports the establishment of a physiological-based pharmacokinetics (PBPK) model to predict the tissue distribution of mirtazapine in the elderly and children. The chemical and pharmacological properties of mirtazapine and absorption, distribution, metabolism, and excretion parameters were collected. The PK-Sim® software was used to develop the PBPK model for predicting the tissue distribution in the adult population extrapolation to the elderly and children. Using the mean fold error (MFE) folding approach, the accuracy of the PBPK model was assessed by comparing the predicted and observed values. The pharmacokinetic data of oral mirtazapine in healthy people were examined for verification. A PBPK model for oral mirtazapine in adults was established and verified using available clinical data. For AUC0-t, Cmax, and T1/2, the MFE ratios between predicted and observed values mainly were between 0.8 and 1.25. Mirtazapine concentrations were higher than venous plasma concentrations in various major tissues. Compared with healthy adults, the elderly and children needed lower dosages of mirtazapine to attain equivalent levels of plasma exposure. The PBPK model was effectively utilized to the pharmacokinetics of mirtazapine and predict its distribution in various age groups. Mirtazapine is used for clinical individualized medication and provides reference and clinical evaluation.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":"104 ","pages":"1-12"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging evidence of trained immunity and inflammatory programming in atherosclerotic cardiovascular disease. 动脉粥样硬化性心血管疾病中训练免疫和炎症程序的新证据。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0149

Ilana S Nazari, Samuel A McFarlane, Meena S Madhur, Allison E Norlander, Edward B Thorp, Matthew J Feinstein

引用次数: 0

Incretin therapy and obesity: current and future pharmacologic possibilities. 肠促胰岛素治疗和肥胖：现在和未来的药理学可能性。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0151

Emory Moss, Kennedy Hawk, Kathrine Lollis, Jennifer N Clements

引用次数: 0

Current clinical application of incretin therapy for obesity management. 肠促胰岛素治疗肥胖症的临床应用现状。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0152

Karlie Skinner, Jennifer N Clements

引用次数: 0

Effect of slow-release hydrogen sulfide donor GYY4137 on vascular smooth muscle and endothelial response in an in vitro ischemia-reperfusion model of rat thoracic aorta. 缓释硫化氢供体GYY4137对体外大鼠胸主动脉缺血再灌注模型血管平滑肌及内皮反应的影响

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 Epub Date: 2025-12-19 DOI: 10.1139/cjpp-2025-0168

Ariyan Teimoori, Halit Güner Orhan, Nargiz Zeynalova, Elif Demirtaş, Oğuzhan Ekin Efe, Huriye Eda Özturan Özer, Selda Emre Aydıngöz

{"title":"Effect of slow-release hydrogen sulfide donor GYY4137 on vascular smooth muscle and endothelial response in an in vitro ischemia-reperfusion model of rat thoracic aorta.","authors":"Ariyan Teimoori, Halit Güner Orhan, Nargiz Zeynalova, Elif Demirtaş, Oğuzhan Ekin Efe, Huriye Eda Özturan Özer, Selda Emre Aydıngöz","doi":"10.1139/cjpp-2025-0168","DOIUrl":"10.1139/cjpp-2025-0168","url":null,"abstract":"Ischemia-reperfusion (IR) injury of vascular grafts used in coronary artery bypass surgery can compromise outcomes. This study examined whether GYY4137, a slow-release hydrogen sulfide donor, protects against IR-induced vascular damage in rat thoracic aorta. Twenty male Sprague-Dawley rats (21-22 months old) were randomly assigned to Control, IR, IR + GYY4137 (100 µM), and IR + GYY4137 (300 µM) groups. To induce IR injury, aortic rings were incubated in nitrogen-gassed saline at 4 °C for 24 h, then exposed to sodium hypochlorite (200 µM) at 37 °C for 30 min. Vascular function was evaluated in organ baths; malondialdehyde, glutathione, and caspase-3 were quantified. IR injury markedly impaired contraction and endothelium-dependent relaxation, which GYY4137 did not restore. In contrast, IR increased malondialdehyde (p = 0.02), which fell to near-control with both 100 µM (p = 0.008) and 300 µM GYY4137 (p = 0.012). IR lowered glutathione (p = 0.012) was restored by 300 µM GYY4137 (p = 0.004). Likewise, caspase-3 rose (p = 0.02) but returned to near-control with both 100 µM (p = 0.004) and 300 µM GYY4137 (p = 0.02). In conclusion, GYY4137 reduces oxidative stress and apoptosis markers without improving vascular dysfunction in an IR model of rat thoracic aorta. This disparity underscores the complex pathophysiology of vascular IR injury, where cellular-level protection does not readily translate to functional recovery.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-10"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High fructose consumption induces cardiac dysfunction and vascular abnormalities. 高果糖摄入会引起心功能障碍和血管异常。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 Epub Date: 2025-12-04 DOI: 10.1139/cjpp-2025-0249

Paramjit S Tappia, Elle Garriock, Bram Ramjiawan, Mohammed H Moghadasian

{"title":"High fructose consumption induces cardiac dysfunction and vascular abnormalities.","authors":"Paramjit S Tappia, Elle Garriock, Bram Ramjiawan, Mohammed H Moghadasian","doi":"10.1139/cjpp-2025-0249","DOIUrl":"10.1139/cjpp-2025-0249","url":null,"abstract":"Fructose is a simple sugar or monosaccharide, which is abundant in nature and commonly used in food industry as a strong natural sweetener. The growing epidemic of high fructose consumption has been linked to increased prevalence of obesity, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and cardiovascular disease. Increasing evidence indicates that high dietary fructose can exert direct effects on the heart as well as the vasculature. Several underlying mechanisms involving metabolic disturbances, oxidative stress, and inflammation have been demonstrated to induce cardiac dysfunction and vascular abnormalities. Accordingly, the intent of this review is to discuss the metabolic consequences of increased fructose consumption and to provide an overview of the mechanisms associated with fructose-enriched diet-induced cardiovascular abnormalities. A description of some novel interventions that attenuate both cardiac and vascular dysfunction subsequent to fructose over consumption is also provided. The high intakes of fructose present a public health hazard, and thus, there is a pressing need to increase public awareness on the harmful health effects, including cardiovascular health, of high intake of foods and beverages enriched with fructose. Furthermore, the supplementation of processed foods and beverages with fructose additives needs regulation.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-10"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cannabivarin and tetrahydrocannabivarin modulate nociception via vanilloid channels and cannabinoid-like receptors in Caenorhabditis elegans. 大麻素和四氢大麻素通过香草样通道和大麻素样受体调节秀丽隐杆线虫的伤害感受。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 Epub Date: 2025-12-04 DOI: 10.1139/cjpp-2025-0243

Nasim Rahmani, Jesus D Castaño, Francis Beaudry

{"title":"Cannabivarin and tetrahydrocannabivarin modulate nociception via vanilloid channels and cannabinoid-like receptors in Caenorhabditis elegans.","authors":"Nasim Rahmani, Jesus D Castaño, Francis Beaudry","doi":"10.1139/cjpp-2025-0243","DOIUrl":"10.1139/cjpp-2025-0243","url":null,"abstract":"Cannabis has attracted growing interest for its therapeutic potential, especially in pain management. This study explores the antinociceptive effects of two promising non-psychoactive cannabinoids, cannabivarin (CBV) and tetrahydrocannabivarin (THCV), using Caenorhabditis elegans, a nematode model that expresses homologs of mammalian cannabinoid and vanilloid receptors. Thermotaxis assays were employed to quantify the antinociceptive effects of CBV and THCV in C. elegans. Wild-type animals were exposed to increasing concentrations of each compound to establish dose-response relationships. To investigate potential molecular targets, additional experiments were performed using mutant strains deficient in vanilloid receptor homologs (OCR-2 and OSM-9) and cannabinoid receptor homologs (NPR-19 and NPR-32). Mass spectrometry-based proteomics combined with network biology analyses were used to identify the biological pathways associated with drug response. Results confirmed that both compounds elicit dose-dependent antinociceptive effects. Mutant analyses support the involvement of vanilloid and cannabinoid signaling pathways in mediating these responses. These findings highlight the potential of CBV and THCV as non-psychoactive analgesic agents and support further research into their mechanisms of action and translational relevance for mammalian pain management.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-13"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vascular dysfunction in renal injury and cognitive dysfunction: the central role of endothelin-1. 肾损伤和认知功能障碍中的血管功能障碍：内皮素-1的中心作用。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0030

Marice K McCrorey, Lada Palygina, Helen M Butler, Justin P Van Beusecum

{"title":"Vascular dysfunction in renal injury and cognitive dysfunction: the central role of endothelin-1.","authors":"Marice K McCrorey, Lada Palygina, Helen M Butler, Justin P Van Beusecum","doi":"10.1139/cjpp-2026-0030","DOIUrl":"10.1139/cjpp-2026-0030","url":null,"abstract":"Chronic kidney disease (CKD) is strongly associated with cognitive impairment and dementia, yet the vascular pathways linking renal injury to cognitive dysfunction remain incompletely defined. The kidney and brain rely on high-flow microvascular circuits and specialized endothelial barriers, rendering both organs vulnerable to endothelial dysfunction. Endothelin-1 (ET-1), a potent vasoactive peptide, is primarily produced by vascular endothelial cells but can also be produced by other cell types including fibroblasts and smooth muscle cells. ET-1 is becoming increasingly recognized as a convergent driver of endothelial and microvascular dysfunction across cardiovascular end-organs. In the kidney, dysregulation of the endothelin (ET) system promotes vasoconstriction, endothelial dysfunction, oxidative stress, and inflammation, accelerating the progression of CKD. In the brain, dysregulation of the ET system contributes to cerebral hypoperfusion, impaired neurovascular coupling, blood-brain-barrier disruption, and neuroinflammation. In this review, we synthesize evidence supporting ET system signaling as a mechanistic and translational bridge between renal and cerebral microvascular dysfunction and discuss how shared cardiometabolic and autoimmune risk factors may amplify ET signaling, thereby worsening kidney-brain outcomes. Lastly, we highlight the therapeutic opportunities and limitations of ET receptor antagonism, emphasizing the need for receptor- and cell-type-specific interventions to mitigate multi-organ vascular injury and preserve cognitive function in patients with CKD.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-14"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stem cells and nanomaterials for cardiac regeneration: integrating multi-omics for precision therapeutics. 干细胞和纳米材料用于心脏再生：整合多组学用于精确治疗。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0173

Amartya Nandi, Gautam Sharma, Elika Verma, Keshav Narayan Alagarsamy, Sanjiv Dhingra

{"title":"Stem cells and nanomaterials for cardiac regeneration: integrating multi-omics for precision therapeutics.","authors":"Amartya Nandi, Gautam Sharma, Elika Verma, Keshav Narayan Alagarsamy, Sanjiv Dhingra","doi":"10.1139/cjpp-2026-0173","DOIUrl":"https://doi.org/10.1139/cjpp-2026-0173","url":null,"abstract":"Cardiovascular diseases (CVDs) are one of the leading causes of mortality worldwide, with myocardial infarction (MI) resulting in irreversible loss of cardiomyocytes and progressive cardiac dysfunction. Clinical interventions primarily restore perfusion and alleviate symptoms yet fail to regenerate the damaged myocardium. Stem cell-based therapeutics have emerged as effective and promising regenerative strategies, largely mediated through paracrine signaling, immunomodulation, and cellular replacement. However, poor cell survival, inadequate engraftment, and functional immaturity of stem cell-derived cardiomyocytes limits their clinical efficacy. Advances in nanotechnology and multi-omics provide powerful tools to address these challenges. Nanomaterials such as gold nanoparticles, graphene derivatives, and MXenes enhance stem cell retention, survival, and electromechanical integration by mimicking the native ECM and enabling targeted delivery of therapeutic molecules. Concurrently, transcriptomic and proteomic profiling offer insights into mechanisms of stem cell-mediated cardiac repair and molecular pathways governing their behavior. Stem cell-based clinical trials demonstrate modest therapeutic benefits, emphasizing the need for integrative, precision-driven strategies. The convergence of stem cell biology, nanomaterial engineering, and multi-omics technologies represents transformative approaches to overcoming limitations and advancing cardiovascular regeneration. This integrative framework holds potential to enable data-driven, personalized therapies to improve functional recovery and long-term outcomes in patients with CVDs.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":"104 ","pages":"1-14"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

QT interval prolongation in the coronary intensive care unit: prevalence, associated drugs, and clinical-genetic risk factors. 冠状动脉重症监护病房QT间期延长：患病率、相关药物和临床遗传危险因素

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0276

Gozde Akturk, Ahmet Anil Baskurt, Ahmet Okay Caglayan, Fazilet Karapinar, Elcin Bora, Ayfer Ulgenalp, Hulya Ellidokuz, Nezihi Baris, Sule Kalkan

{"title":"QT interval prolongation in the coronary intensive care unit: prevalence, associated drugs, and clinical-genetic risk factors.","authors":"Gozde Akturk, Ahmet Anil Baskurt, Ahmet Okay Caglayan, Fazilet Karapinar, Elcin Bora, Ayfer Ulgenalp, Hulya Ellidokuz, Nezihi Baris, Sule Kalkan","doi":"10.1139/cjpp-2025-0276","DOIUrl":"10.1139/cjpp-2025-0276","url":null,"abstract":"We aimed to investigate the prevalence of QTc interval prolongation (QTcIP), QTc-prolonging drug exposure, and associated clinical and genetic risk factors in adult patients hospitalized in the Coronary Intensive Care Unit. This observational cohort study included 207 patients hospitalized for ≥24 h. Clinical, laboratory, and electrocardiographic data were analyzed, and QTcIP was defined using sex-specific thresholds (>470 ms in women, >450 ms in men). In addition, 33 genes were analyzed using an arrhythmia next-generation sequencing panel. QTcIP was detected in 31 patients (15.0%). Proton pump inhibitors were the most commonly used QTc-prolonging drugs (96.1%), while QTcIP was most frequently observed among patients receiving sertraline; however, the number of exposed patients was small. Acute coronary syndrome, myocardial infarction, and the presence of hypertension were significantly associated with QTcIP (p < 0.05). In two patients with QTcIP, likely pathogenic, heterozygous variants were identified in the SCN5A and LMNA genes. In four additional patients, variants of unknown significance were detected in the RYR2, TTN, KCNH2, and GPD1L genes. These findings suggest that QTc prolongation in clinical practice may occur in the context of diverse clinical conditions and rare genetic variants. Careful clinical monitoring remains essential when initiating QTc-prolonging medications, particularly in patients with cardiovascular comorbidities.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-11"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0