Canadian journal of physiology and pharmacology最新文献_第7页

Different responses to homocysteine in primary endothelial cells and an immortalized endothelial cell line. 原代内皮细胞和永生化内皮细胞系对同型半胱氨酸的不同反应。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0250

Zuzana Matiko, Roman Moravčík, Michal Zeman

{"title":"Different responses to homocysteine in primary endothelial cells and an immortalized endothelial cell line.","authors":"Zuzana Matiko, Roman Moravčík, Michal Zeman","doi":"10.1139/cjpp-2025-0250","DOIUrl":"10.1139/cjpp-2025-0250","url":null,"abstract":"Endothelial cells play a key role in maintaining vascular homeostasis, and disruption of their function contributes to endothelial dysfunction. The underlying mechanisms have been studied using primary endothelial cells (HUVEC) and hybrid endothelial cell line EA.hy926, and their responses to disrupting agents should be similar. In this study, we investigated the effects of elevated homocysteine (HCY) concentrations, a risk factor for endothelial dysfunction development, in both cell types. Using multiple approaches, the inhibitory effect of HCY was consistently observed in HUVEC. In contrast, EA.hy926 cells exhibited increased proliferation and viability at lower doses, whereas the highest dose (10 mM) was inhibitory to both cell types. The bimodal and stimulatory effect of HCY in EA.hy926 cells was abolished by aminooxyacetic acid, a dominant inhibitor of cystathionine beta-synthase suggesting that decreased HCY levels and the formation of glutathione and hydrogen sulfide protected these cells. No such effect was found in HUVEC. The PI3K/Akt and MAPK/ERK signaling pathways were differentially activated in both models, suggesting their differing contributions to the HCY response. These findings reveal the cell-specific mechanisms of HCY-induced endothelial disruption, contributing to a better understanding of the mechanisms underlying endothelial dysfunction.","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":"145917091","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

Personalized pain management: The use of pharmacogenomics in pain treatment strategies. 个性化疼痛管理：药物基因组学在疼痛治疗策略中的应用。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0304

Erika N Scott, Laura P Simonson, Catrina M Loucks

{"title":"Personalized pain management: The use of pharmacogenomics in pain treatment strategies.","authors":"Erika N Scott, Laura P Simonson, Catrina M Loucks","doi":"10.1139/cjpp-2025-0304","DOIUrl":"10.1139/cjpp-2025-0304","url":null,"abstract":"Pain is commonly experienced among Canadians but can be difficult to treat due to complex mechanisms. Several medications used for analgesia (e.g., acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, antidepressants, anticonvulsants), can have variable responses, limiting their safety and effectiveness. Pharmacogenomics studies have uncovered genetic variation found within drug processing (i.e., pharmacokinetic) and response (i.e., pharmacodynamic) pathways that are linked to the development of ineffectiveness and/or adverse effects to analgesics. As a result, several gene-drug associations with strong evidence have been incorporated into clinical practice guidelines. For example, individuals are currently recommended to undergo genetic testing for variation within CYP2C9 (adverse effects to some NSAIDs and anticonvulsants), CYP2D6 (ineffectiveness/adverse effects to some opioids, antidepressants, and anticonvulsants), CYP2C19 (ineffectiveness/adverse effects to some antidepressants), CYP2B6 (adverse effects to some antidepressants), and HLA-A and HLA-B (adverse effects to some anticonvulsants) so that modifications can be made to reduce the likelihood of treatment ineffectiveness/adverse effects. As there is limited evidence for treatment recommendations for all analgesics, and in children and minority ancestral groups, further pharmacogenomics studies are needed to identify additional genetic variation that contributes to undesirable outcomes. Ultimately, pharmacogenomics is helping to develop personalized pain management strategies to improve pain treatment outcomes for all patients.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-10"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194114","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

Opioid agonist treatment dispensing trends between 2018 and 2022 across six Canadian provinces. 2018年至2022年加拿大六个省阿片类激动剂治疗配药趋势

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0171

Ria Garg, Bisola Hamzat, Grace Cheung, Dean Eurich, Jean-Luc Kaboré, Louis de Léséleuc, Zhaoyu Liu, Houssem Missaoui, Jason R Randall, Dana Shearer, David Stock, Joanna Yang, Tara Gomes

{"title":"Opioid agonist treatment dispensing trends between 2018 and 2022 across six Canadian provinces.","authors":"Ria Garg, Bisola Hamzat, Grace Cheung, Dean Eurich, Jean-Luc Kaboré, Louis de Léséleuc, Zhaoyu Liu, Houssem Missaoui, Jason R Randall, Dana Shearer, David Stock, Joanna Yang, Tara Gomes","doi":"10.1139/cjpp-2025-0171","DOIUrl":"10.1139/cjpp-2025-0171","url":null,"abstract":"Opioid agonist treatment (OAT) is the recommended first-line therapy for individuals with opioid use disorder. The availability of different products and prescribing guidance for OAT has rapidly evolved in recent years. Therefore, we conducted a repeated cross-sectional study using pharmacy dispensing data from six Canadian provinces to examine trends in methadone and buprenorphine use between January 2018 and December 2022. Monthly population-adjusted rates of OAT recipients were calculated by province, and annual cohorts were stratified by demographic characteristics and OAT type. Prevalence of OAT use varied across provinces, ranging from 1.03 per 1000 in Quebec to 3.59 per 1000 in British Columbia. Increases in OAT use between 2018 and 2022 were observed in Alberta (3.00-3.75 per 1000) and Manitoba (1.68-2.39 per 1000), while rates remained relatively stable elsewhere. OAT use was highest among adults aged 25-44 years, males, and residents of lower-income neighbourhoods. A notable shift toward buprenorphine prescribing was observed across all provinces, with 45%-74% of OAT recipients dispensed a buprenorphine product in 2022. These cross-provincial differences in OAT rates likely reflect variations in opioid use disorder prevalence, prescribing practices, and access to care.","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":"146212145","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

Placental hypoxia and oxidative stress responses to smokeless tobacco use in Alaska Native participants in the MAW study. 在MAW研究中，阿拉斯加土著参与者对无烟烟草使用的胎盘缺氧和氧化应激反应。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0271

Katherine M Kennedy, Jessica G Wallace, Kathryn R Koller, Christi A Patten, Timothy K Thomas, Neil J Murphy, Christie A Flanagan, Christine A Hughes, Alison C Holloway, Deborah M Sloboda

{"title":"Placental hypoxia and oxidative stress responses to smokeless tobacco use in Alaska Native participants in the MAW study.","authors":"Katherine M Kennedy, Jessica G Wallace, Kathryn R Koller, Christi A Patten, Timothy K Thomas, Neil J Murphy, Christie A Flanagan, Christine A Hughes, Alison C Holloway, Deborah M Sloboda","doi":"10.1139/cjpp-2025-0271","DOIUrl":"10.1139/cjpp-2025-0271","url":null,"abstract":"Cigarette smoking is associated with numerous adverse pregnancy outcomes, due in part to polycyclic aromatic hydrocarbons and free radicals produced by combustion. Less is known about the impact of smokeless tobacco (ST) use during pregnancy. Alaska Native women report higher rates of cigarette and ST use during pregnancy than non-Native women. We investigated oxidative stress and hypoxia pathways in term placentae from Alaska Native women who did (commercial or iqmik; n = 10) or did not (n = 18) use ST during pregnancy. Despite substantial maternal exposure to nicotine, placentae of women who used ST had similar mRNA levels of antioxidant enzymes and markers of hypoxia compared to those who did not use tobacco. Although mRNA levels of angiogenesis markers vegf and vegfr2 were similar between groups, vegfr1 mRNA levels are increased in placentae of women using ST compared to women who did not use tobacco. Together these results suggest that, while ST use may not have as significant an effect on oxidative stress pathways in the placenta as cigarette smoking, an effect is present. It is not clear what this limited effect may have on the developing fetus.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-7"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917060","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

Next-generation therapeutics and renaissance of legacy drugs targeting the endothelin system. 针对内皮素系统的新一代疗法和传统药物的复兴。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0068

Anthony P Davenport, Majid Anwar, Rhoda E Kuc, Lena Brynne, Anne-Kristina Mercier, Magnus Åstrand, Peter J Greasley, Philip Ambery, Janet J Maguire

{"title":"Next-generation therapeutics and renaissance of legacy drugs targeting the endothelin system.","authors":"Anthony P Davenport, Majid Anwar, Rhoda E Kuc, Lena Brynne, Anne-Kristina Mercier, Magnus Åstrand, Peter J Greasley, Philip Ambery, Janet J Maguire","doi":"10.1139/cjpp-2026-0068","DOIUrl":"https://doi.org/10.1139/cjpp-2026-0068","url":null,"abstract":"Endothelin-1 (ET-1) was discovered in 1988, followed by identification of ETA and ETB receptors in 1990, enabling rapid development of the first endothelin receptor antagonists (bosentan, ambrisentan, and macitentan) for pulmonary arterial hypertension, a condition marked by elevated ET-1. Nearly a decade later, a new therapeutic wave began with the ETB agonist sovateltide (2021) for cerebral ischemic stroke, demonstrating the benefits of ETB activation. More recent antagonist development has shifted toward ETA-selective agents to preserve ETB function. Clazosentan (ETA) for cerebral vasospasm and aprocitentan (ETA/ETB) for resistant hypertension extended endothelin-targeted therapy into more common diseases. In kidney disease, sparsentan (AT1/ETA) and atrasentan (ETA) have both been approved for IgA nephropathy, with atrasentan succeeding after earlier failed trials. Repurposing has become a major strategy in G protein-coupled receptor drug development. This review outlines approaches for identifying legacy endothelin compounds suitable for new indications, using zibotentan, now combined with dapagliflozin to reduce fluid retention as an example. Kidney disease remains a central focus of current trials, which include new ETA-selective diosuxentan and monoclonal antibody getagozumab, and the ETB peptide antagonist vodudeutentan. The review summarizes recent pharmacology and clinical data and highlights emerging strategies for next-generation endothelin-pathway therapeutics.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":"104 ","pages":"1-16"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359715","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

Correction: Pharmacological safety of dimethoxy curcumin-human serum albumin conjugate for potential therapeutic purpose. 更正：用于潜在治疗目的的二甲氧基姜黄-人血清白蛋白偶联物的药理学安全性。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0077

Mejo C Korah, V S Harikrishnan, S Deepa, Anil Arya, A Sabareeswaran, P V Mohanan, Lissy K Krishnan

引用次数: 0

Inhibition of ADAMTS1 and ATP citrate lyase attenuates connexin-43 degradation and HFrEF. 抑制ADAMTS1和ATP柠檬酸裂解酶可减弱连接蛋白43的降解和HFrEF。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0162

Yu-Ting Zheng, Suresh C Tyagi

{"title":"Inhibition of ADAMTS1 and ATP citrate lyase attenuates connexin-43 degradation and HFrEF.","authors":"Yu-Ting Zheng, Suresh C Tyagi","doi":"10.1139/cjpp-2025-0162","DOIUrl":"10.1139/cjpp-2025-0162","url":null,"abstract":"Human genome- and transcriptome-wide analyses revealed that 56% of heart failure cases have unknown causes. Interestingly, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is one of those causes. Previously, we have shown a robust increase in the degradation of a disintegrin and metalloproteinase (ADAM) and connexin-43 (Cx43) in human end-stage heart failure with reduced ejection fraction (HFrEF). We also observed Cx43 degradation and blood-heart barrier leakage during HFrEF in mice. Although Cx43 coordinates mitochondrial fusion-fission with myocyte contraction-relaxation, respectively, the mechanism is unclear. Interestingly, inhibition of mitochondrial ATP citrate lyase (ACYLi, a lipid-lowering agent) causes HFpEF, but its role in HFrEF is unknown. We hypothesize that during HFrEF, activation of ADAMTS1 degrades Cx43, causing dyssynchronous endothelial-myocyte-mitochondrial contraction coupling, as well as myocyte slippage during contraction and HFrEF. Because HFrEF is more prevalent in males than females, we created chronic cardiopulmonary volume overload by aorta-vena cava fistula (AVF) below the kidney in male wild-type (C57BL/6J) mice aged 12 weeks. By serial echocardiography, we observed HFrEF after 16 weeks. The ADAMTS1 inhibitor (epigallocatechin gallate) or ACYLi (hydroxycitric acid lactone) was administered in drinking water at the same time as AVF. Also, to assess interoceptive inhibition via Piezo channels, we ganglionally denervated the heart prior to AVF. By gel-specific substrate zymography, we measured NGAL, MMP2, MMP9, ADAMTS1, ADAMTS14, and TMPRSS2. The levels of Cx43, ADAMTS1, mitochondrial Drp1 (fission protein), and ACYL were measured by Western blot analysis. The results suggest that ADAMTS1 is activated during HFrEF. Connexin-43 degradation and mitochondrial mitophagy were increased by an increase in Drp1. The therapeutic effects of ADAMTS1 and ACYL inhibitors for systolic HFrEF are suggested.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":"104 ","pages":"1-7"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637987","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

Metabolic therapy for cardiovascular diseases with propionyl L-carnitine. 丙酰左旋肉碱对心血管疾病的代谢治疗。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0241

Naranjan S Dhalla, Khushman Kaur, Vijayan Elimban, Paul Ganguly

{"title":"Metabolic therapy for cardiovascular diseases with propionyl L-carnitine.","authors":"Naranjan S Dhalla, Khushman Kaur, Vijayan Elimban, Paul Ganguly","doi":"10.1139/cjpp-2025-0241","DOIUrl":"10.1139/cjpp-2025-0241","url":null,"abstract":"Propionyl L-carnitine (PPLC), a short-chain fatty acid derivative of carnitine, has been reported to produce beneficial effects in various cardiovascular diseases such as maladaptive cardiac hypertrophy, heart failure, ischemic heart disease, different types of cardiomyopathies and peripheral artery disease. Although all these cardiovascular diseases have diverse epidemiology and pathophysiology, both clinical and preclinical studies have indicated the role of oxidative stress, Ca2+-handling defects and metabolic abnormalities in their development and progression. In heart failure due to myocardial infarction, treatment with PPLC attenuated the inhibition of Na+-K+ ATPase and Na+-Ca2+ exchange activities. PPLC therapy of animals with diabetic cardiomyopathy improved Ca2+-handling abnormalities in cardiomyocytes by affecting the entry of Ca2+ through sarcolemma and regulating the sarcoplasmic reticular Ca2+-pump activities. The improvement of cardiac function recovery by PPLC treatment in ischemia-reperfused hearts was associated with its ability to antagonize the deleterious effects of palmitoyl L-carnitine on Ca2+-handling proteins. Treatment of peripheral artery disease with PPLC increased blood flow by affecting the vascular endothelium and smooth muscle functions in lower limbs. These observations support the view that PPLC improves cardiovascular function in diseased conditions by promoting mitochondrial metabolism, reducing oxidative stress and preventing Ca2+-handling abnormalities.","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":"147321372","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

Abstracts for The 2025 Scientific Meeting of the Canadian Society of Pharmacology and Therapeutics. 加拿大药理学和治疗学学会2025年科学会议摘要。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0282

引用次数: 0

Association of stromal cell-derived factor 1α and interferon-γ-induced protein 10 with Fontan pathophysiology. 基质细胞衍生因子1α和干扰素γ诱导蛋白10与Fontan病理生理的关系。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0238

Ashim K Bagchi, Yixiu Liu, Sanjiv Dhigra, Amir Ravandi, Pawan K Singal, Ashish H Shah

{"title":"Association of stromal cell-derived factor 1α and interferon-γ-induced protein 10 with Fontan pathophysiology.","authors":"Ashim K Bagchi, Yixiu Liu, Sanjiv Dhigra, Amir Ravandi, Pawan K Singal, Ashish H Shah","doi":"10.1139/cjpp-2025-0238","DOIUrl":"10.1139/cjpp-2025-0238","url":null,"abstract":"Despite restoration of systemic and pulmonary circulation and normalized oxygen saturation, patients with Fontan circulation experience frailty, exercise intolerance, and impaired exercise hemodynamics. Altered cytokine-chemokine profiles have been reported, but their relationship with Fontan pathophysiology remains poorly defined. Adult Fontan patients and matched controls were assessed for frailty, cardiopulmonary exercise capacity, and resting/exercise-augmented hemodynamics. Plasma cytokine-chemokine concentrations were measured using multiplex ELISA. Twenty Fontan patients (mean age 28.8 ± 9.8 years; 35% female) and 20 controls (29.7 ± 6.0 years; 30% female) were studied. Fontan patients had longer 5 × sit-to-stand test (9.6 ± 3.1 vs. 5.7 ± 1.3 s; p < 0.0001), lower VO2max (% predicted), and reduced stroke index, cardiac index, and cardiac power index. TNF-α, IL-1β, IL-6, IFN-γ, IL-8, IP-10, MCP-1, and SDF-1α were elevated in Fontan patients, while IL-10 and MIP-1α were not different. SDF-1α and IP-10 correlated with frailty, impaired oxygen uptake, and hemodynamic parameters. Elevated SDF-1α and IP-10 are associated with frailty and impaired exercise hemodynamics in Fontan patients. These novel findings suggest a role for inflammation in Fontan-associated dysfunction and warrant further investigation.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-10"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148194531","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