Canadian journal of physiology and pharmacology最新文献_第8页

Major adverse events related to atorvastatin calcium hydrocarbons: pharmacovigilance study in the FAERS database. 与阿托伐他汀钙碳氢化合物相关的主要不良事件：FAERS数据库中的药物警戒研究。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0288

Kun Yuan, Zi-Tong Huang, Ri-Lang Liu, Zi-Wen Liu, Jie Lv, Can-Can Li, Qian Xu

{"title":"Major adverse events related to atorvastatin calcium hydrocarbons: pharmacovigilance study in the FAERS database.","authors":"Kun Yuan, Zi-Tong Huang, Ri-Lang Liu, Zi-Wen Liu, Jie Lv, Can-Can Li, Qian Xu","doi":"10.1139/cjpp-2025-0288","DOIUrl":"10.1139/cjpp-2025-0288","url":null,"abstract":"This study analyzed safety data for atorvastatin calcium hydrate (ACH) using real-world adverse event reports from the U.S. FDA Adverse Event Reporting System (FAERS, 2004-2024) and the European Medicines Agency's EudraVigilance (EV, 2002-2024). A total of 104 798 ACH-related reports were included: 67 498 from FAERS and 37 300 from EV. Four signal detection algorithms (ROR, PRR, BCPNN, and MGPS) identified 597 significant positive signals, 356 in FAERS and 241 in EV, covering 27 system organ classes. FAERS signals mainly involved metabolic, cardiac, and nervous system disorders, while EV was dominated by examination abnormalities (66 signals, 27.39%) and musculoskeletal disorders (29 signals, 12.03%). Rhabdomyolysis and drug-induced liver injury were major designated medical events in both databases. EV also identified liver failure, hepatocellular injury, and death (1833 cases, 4.91%) as key serious outcomes. Stratified analyses showed elderly patients in FAERS had higher risks of type 2 diabetes and emotional distress. In EV, patients aged ≥65 years accounted for 34.12%, females 49.83% versus males 37.21%, and severe cases reached 94.50%. The study recommends close clinical monitoring for rhabdomyolysis, liver injury, and fatal outcomes, with special attention to liver function and muscle symptoms in elderly, diabetic, emotionally distressed, and female patients.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-15"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834111","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

Microemboli model of vascular cognitive impairment/dementia (VCID) presents with long-term brain tissue hypoxia: relevance to the endothelin (ET) system. 血管性认知障碍/痴呆（VCID）微栓子模型表现为长期脑组织缺氧：与内皮素（ET）系统的相关性

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0350

Weiguo Li, Eda Karakaya, Jazlyn Edwards, Alice Li, Marice K McCrorey, Helen M Butler, Justin P Van Beusecum, Sarah Jamil, Yasir Abdul, Adviye Ergul

{"title":"Microemboli model of vascular cognitive impairment/dementia (VCID) presents with long-term brain tissue hypoxia: relevance to the endothelin (ET) system.","authors":"Weiguo Li, Eda Karakaya, Jazlyn Edwards, Alice Li, Marice K McCrorey, Helen M Butler, Justin P Van Beusecum, Sarah Jamil, Yasir Abdul, Adviye Ergul","doi":"10.1139/cjpp-2025-0350","DOIUrl":"10.1139/cjpp-2025-0350","url":null,"abstract":"Diabetes increases the risk of vascular contributions to cognitive impairment and dementia (VCID). Using a microemboli (ME) model, we found that diabetic rats experience more severe white matter damage and progressive cognitive decline than controls. Moreover, the restoration of endothelial function before ME injection prevents VCID in diabetes. Given that diabetes mediates early endothelial dysfunction, activates the endothelin (ET) system, and the post-mortem brain (b) ET-1 levels correlate with tissue hypoxia in dementia patients, this study investigated the relationship between ET system, hypoxia, and neuroinflammation in this clinically relevant VCID model. While there were no ME-mediated changes or differences between control and diabetic groups in plasma and bET-1 levels, bET-1 levels correlated with hypoxia markers. ETAR expression was reduced by the ISMN (75 mg/kg/day) and cilostazol (60 mg/kg/day) treatment. On the other hand, ETBR expression was lower in the sham diabetic group compared to the sham controls, and ME injection did not have further effect. The treatment restored ETBR expression to comparable levels in the control sham group. These findings suggest a link between the ET system, hypoxia, and neuroinflammation in diabetic VCID. Modulating the ET system may be a viable therapeutic strategy to improve vascular function and prevent VCID.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","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":"147353991","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

12th Annual Meeting of the North American Section of the International Academy of Cardiovascular Sciences (IACS-NAS). 国际心血管科学学会（IACS-NAS）北美分会第12届年会。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0197

引用次数: 0

Role of endogenous incretin hormones, GLP-1 and GIP, in cardiovascular physiology. 内源性肠促胰岛素激素、GLP-1和GIP在心血管生理中的作用。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0163

Khushali Trivedi, Vernon W Dolinsky

{"title":"Role of endogenous incretin hormones, GLP-1 and GIP, in cardiovascular physiology.","authors":"Khushali Trivedi, Vernon W Dolinsky","doi":"10.1139/cjpp-2025-0163","DOIUrl":"10.1139/cjpp-2025-0163","url":null,"abstract":"Obesity, type 2 diabetes (T2D), and cardiovascular disease are closely related conditions contributing to the global rise in cardiometabolic disease. Incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have emerged as critical regulators of glucose metabolism, pancreatic function, and cardiovascular physiology. However, despite increasing clinical use of GLP-1 receptor agonists and dual GLP-1/GIP agonists, the precise mechanisms by which endogenous incretins influence cardiovascular tissues remain incompletely understood, particularly in the context of obesity and T2D. This review explores the signalling mechanisms and physiological actions of natural endogenous GLP-1 and GIP, with a focus on cardiovascular physiology. Endogenous GLP-1 promotes insulin secretion, β-cell survival, and appetite suppression, and exerts protective effects on the endothelium. GLP-1 also reduces inflammation, enhances nitric oxide production, and improves myocardial glucose utilization during ischemia. Endogenous GIP is involved in insulin secretion, β-cell survival, and adipogenesis. In obesity and T2D, incretin secretion and insulinotropic effects are altered. The therapeutic potential of GLP-1 receptor agonists and emerging dual GLP-1/GIP agonists has been shown to aid in managing metabolic dysfunction and, more recently, in preventing cardiovascular complications.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-13"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997331","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

Incretins in Action: Unlocking New Frontiers from Bench to Bedside. 胰岛素在行动：解锁新领域从实验室到床边。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0110

Nicholas W Carris, Kevin Cowart

引用次数: 0

Electrocardiographic screening for left atrial enlargement in dogs: derivation and validation of an algorithm combining lead II P-wave duration and the Morris index.

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0057

José Luís de Sousa Santana, Marina Pinto Sanches, Laecio da Silva Moura, Yanca Bizerra Souza, Renan Paraguassu de Sá Rodrigues, Ycaro Kylldary Macedo, Eduardo Antônio Lima Oliveira, Bruno Leandro Maranhão Diniz, Cristiane Coelho Costa, Flávio Ribeiro Alves

{"title":"Electrocardiographic screening for left atrial enlargement in dogs: derivation and validation of an algorithm combining lead II P-wave duration and the Morris index.","authors":"José Luís de Sousa Santana, Marina Pinto Sanches, Laecio da Silva Moura, Yanca Bizerra Souza, Renan Paraguassu de Sá Rodrigues, Ycaro Kylldary Macedo, Eduardo Antônio Lima Oliveira, Bruno Leandro Maranhão Diniz, Cristiane Coelho Costa, Flávio Ribeiro Alves","doi":"10.1139/cjpp-2026-0057","DOIUrl":"https://doi.org/10.1139/cjpp-2026-0057","url":null,"abstract":"Combining electrocardiographic measurements may improve identification of dogs requiring echocardiographic assessment. This retrospective diagnostic accuracy study derived a three-category algorithm in 150 dogs and evaluated it in 50 separate validation dogs. Three observers independently measured lead II P-wave duration and the V1 Morris index, with observer A providing the primary analysis. Left atrium-to-aorta ratio (LA/Ao) ≥ 1.6 was the primary outcome; normalized left ventricular internal diameter in diastole (LVIDDN) ≥ 1.7 was evaluated independently as a secondary outcome. Thresholds from 114 reference dogs were 48 and 52 ms for P duration and 3.04 mV·ms for Morris. Positive triage comprised intermediate and high categories. Primary-outcome sensitivity and specificity were 90.6% and 50.0% in derivation and 100% and 85.7% in validation. Validation sensitivity had a 95% confidence interval of 88.1%-100%. The ordinal algorithm area under the curve was 0.961 in validation, compared with 0.868 for P and 0.844 for Morris; paired differences were not significant after Holm adjustment. Secondary-outcome validation sensitivity and specificity were 88.0% and 60.0%. The algorithm provided complementary detection of left atrial enlargement and reproducible measurements across observers, supporting further evaluation as an adjunct to echocardiographic triage.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":"104 ","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":"149262994","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

New hypoglycemic effects of indorenate mediated by the 5-HT1a and 5-HT2a receptors: in vivo and in silico studies. 吲哚酸由5-HT1a和5-HT2a受体介导的新降糖作用：体内和计算机研究

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0027

Abraham Giacoman-Martínez, Julio César Almanza-Pérez, Francisco Javier Alarcón-Aguilar, Wendoline Rosiles-Alanís, Santiago Villafaña, Rodrigo Romero-Nava, Karla Aidee Aguayo-Cerón, Fengyang Huang, Enrique Hong

{"title":"New hypoglycemic effects of indorenate mediated by the 5-HT1a and 5-HT2a receptors: in vivo and in silico studies.","authors":"Abraham Giacoman-Martínez, Julio César Almanza-Pérez, Francisco Javier Alarcón-Aguilar, Wendoline Rosiles-Alanís, Santiago Villafaña, Rodrigo Romero-Nava, Karla Aidee Aguayo-Cerón, Fengyang Huang, Enrique Hong","doi":"10.1139/cjpp-2025-0027","DOIUrl":"10.1139/cjpp-2025-0027","url":null,"abstract":"The treatment of metabolic syndrome (MS), characterized by type 2 diabetes, obesity, dyslipidemias, and cardiovascular problems, requires integral treatment. In addition to its central activity, serotonin also has peripheral effects, implying regulation of blood glucose and insulin levels. Indorenate is a serotonin analog with antihypertensive properties and possible activity on the metabolism of carbohydrates. However, its effect on glucose levels has not been explored, which is relevant in searching for the indorenate's potential as an alternative to treatment of MS. This investigation aimed to study the effects of indorenate on glycemia through in vivo and in silico assays. In normal rats, indorenate was co-administrated with two serotoninergic antagonists: pelanserin (5-HT2a antagonist) and WAY-100635 (5-HT1a antagonist). Indorenate caused a hypoglycemic effect in normal rats. Pelanserin and WAY-100635 inhibited this effect. In diabetic rats, indorenate increased insulin levels. In addition, indorenate decreased glycemia in an euglycemic clamp test, while pelanserin inhibited this effect. In silico, indorenate exhibited a higher affinity and interactions than serotonin for 5-HT2a and 5HT1a receptors. The data suggest that the hypoglycemic effect of indorenate requires the participation of the 5-HT2a receptor and partially of the 5-HT1a receptor. Finding drugs with beneficial multimodal effects for blood pressure and glycemic control, such as indorenate, might be relevant for treating MS and its associated pathologies.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-12"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573262","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

Clozapine and pharmacogenomics testing: opportunities and challenges for personalized treatment in schizophrenia. 氯氮平和药物基因组学测试：精神分裂症个性化治疗的机遇和挑战。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 Epub Date: 2025-12-01 DOI: 10.1139/cjpp-2025-0174

Muhammad Abdur Rahman Khoodoruth, Mohamed Adil Shah Khoodoruth

{"title":"Clozapine and pharmacogenomics testing: opportunities and challenges for personalized treatment in schizophrenia.","authors":"Muhammad Abdur Rahman Khoodoruth, Mohamed Adil Shah Khoodoruth","doi":"10.1139/cjpp-2025-0174","DOIUrl":"10.1139/cjpp-2025-0174","url":null,"abstract":"Clozapine remains the gold standard for treatment-resistant schizophrenia (TRS), offering unparalleled efficacy but accompanied by significant interindividual variability in response and risk of severe adverse effects. Pharmacogenomics (PGx), the study of how genetic variations influence drug response, has transformed treatment for other medications like warfarin but remains underutilized in clozapine prescribing. This review synthesizes current evidence on the potential of PGx to enhance clozapine treatment by improving the prediction of therapeutic response, metabolism, and adverse drug reactions. Key genetic markers, such as variants in serotonin receptor genes (e.g., HTR2A and HTR3A), metabolism-related enzymes (CYP1A2), and immune-related genes (HLA-DQB1 and HLA-B*59:01), show promise in guiding personalized clozapine prescribing. However, economic, educational, and systemic challenges, particularly in Canada, hinder broader implementation. PGx testing in psychiatry is available but lacks standardization in cost, accessibility, and test panels. Additionally, PGx research remains Eurocentric, with limited data on Indigenous and diverse populations. In Canada, initiatives like Go-PGx reflect growing national interest, but mental health applications remain minimal. Bridging research with practice through inclusive research, clinician education, artificial intelligence and machine learning, and cost-effectiveness analyses may help unlock PGx's full potential for over 200 000 Canadians living with schizophrenia.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-6"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367482","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

Investigating the combined effects of jadomycin B and celecoxib against triple-negative breast cancer using zebrafish larval xenografts. 研究jadomycin B和塞来昔布联合治疗斑马鱼异种移植三阴性乳腺癌的效果。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 Epub Date: 2025-12-23 DOI: 10.1139/cjpp-2025-0117

Hailey M Stack, Michael G Morash, Brendan T McKeown, Lee D Ellis, Kerry B Goralski

{"title":"Investigating the combined effects of jadomycin B and celecoxib against triple-negative breast cancer using zebrafish larval xenografts.","authors":"Hailey M Stack, Michael G Morash, Brendan T McKeown, Lee D Ellis, Kerry B Goralski","doi":"10.1139/cjpp-2025-0117","DOIUrl":"10.1139/cjpp-2025-0117","url":null,"abstract":"Breast cancer affects one in eight Canadian women over their lifetime. Triple-negative breast cancer (TNBC) represents 10%-20% of all advanced stage breast cancers, often developing multidrug resistance (MDR), commonly resulting in treatment failure. Jadomycin B (JB), a natural product of Streptomyces venezuelae, maintains cytotoxicity against MDR TNBCs, and its activity is enhanced when combined with selective cyclooxygenase-2 inhibitor, celecoxib (CXB) in vitro. Our objectives were to evaluate the toxicity and anticancer effects of JB combined with CXB using zebrafish larval xenografts as a model system. Fluorescent human TNBC MDA-MB-231 cells (231-enhanced green fluorescent protein (EGFP)) were generated and characterized for zebrafish larval xenografts. A maximum tolerated dose (MTD) in zebrafish larvae were determined for JB (20 µM) and CXB (5 µM). Zebrafish embryos were xenotransplanted with 50-100 231-EGFP cells and treated with the MTDs of JB and CXB alone or in combination. The combination of JB and CXB resulted in a 75% reduction in 231-EGFP fluorescence intensity, significantly higher than reductions caused by either drug alone (39% for JB, 15% for CXB) (p < 0.05). This study demonstrates that combining JB with CXB enhances anticancer activity in a zebrafish larval xenograft model of human TNBC, validating effects previously determined in vitro.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-8"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502176","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

Untangling the heart-brain connection in Parkinson's disease: emerging mechanisms and models. 解开帕金森病的心脑连接：新出现的机制和模型。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0223

Alessandra Martello, Vincenzo Lionetti

{"title":"Untangling the heart-brain connection in Parkinson's disease: emerging mechanisms and models.","authors":"Alessandra Martello, Vincenzo Lionetti","doi":"10.1139/cjpp-2025-0223","DOIUrl":"10.1139/cjpp-2025-0223","url":null,"abstract":"Cardiovascular autonomic dysfunction (CVAD) is a prevalent yet underrecognized nonmotor manifestation of Parkinson's disease (PD) that adversely affects morbidity, prognosis, and quality of life. Framed by the heart-brain axis, this review examines bidirectional interactions between neurodegeneration and cardiovascular control, synthesizing clinical and preclinical evidence from 2015 to 2025. We searched PubMed for English-language studies addressing autonomic involvement in PD and cardiovascular outcomes; of 1035 records identified, more than 240 met inclusion criteria following removal of duplicates, commentaries, and off-topic articles. Consistent clinical observations include orthostatic hypotension, diminished heart rate variability, impaired baroreflex sensitivity, and blood pressure lability, though heterogeneity in acquisition protocols and analytics limits comparability. Experimental models reveal mechanistic leads but often lack integration of central and peripheral endpoints, sex-inclusive cohorts, aging variables, and longitudinal designs. We highlight methodological constraints, particularly the interpretive limits of HRV, anesthesia effects in preclinical work, and inconsistent preprocessing, and outline priorities for standardized, multimodal approaches that couple neural markers with cardiovascular readouts. Advancing an integrative, translational framework may enable earlier diagnosis, robust autonomic biomarkers, risk stratification across \"body-first\" and \"brain-first\" trajectories, and targeted interventions, including neuromodulation and metabolic strategies, aimed at mitigating CVAD and potentially modifying PD progression.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-19"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548187","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