Canadian journal of physiology and pharmacology最新文献

Pseudolymphoma Associated with Calcium Channel Blockers: A FAERS Disproportionality Analysis Comparing Dihydropyridines and Non-Dihydropyridines. 与钙通道阻滞剂相关的假性淋巴瘤：比较二氢吡啶和非二氢吡啶的FAERS歧化分析。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-05-07 DOI: 10.1139/cjpp-2025-0406

Connor Frey

{"title":"Pseudolymphoma Associated with Calcium Channel Blockers: A FAERS Disproportionality Analysis Comparing Dihydropyridines and Non-Dihydropyridines.","authors":"Connor Frey","doi":"10.1139/cjpp-2025-0406","DOIUrl":"https://doi.org/10.1139/cjpp-2025-0406","url":null,"abstract":"Introduction Calcium channel blockers (CCBs), particularly amlodipine, are among the most widely prescribed antihypertensive agents globally. However, no comprehensive disproportionality analysis has quantified this association. This pharmacovigilance study utilized the FDA Adverse Event Reporting System (FAERS) to evaluate the reporting association between CCBs and pseudolymphoma. Methods The FAERS database was parsed through its 14,104,743 adverse event reports. Five CCBs were evaluated: three dihydropyridines (amlodipine, nifedipine, felodipine) and two non-dihydropyridines (diltiazem, verapamil). Disproportionality was quantified using reporting odds ratios. The MedDRA preferred term \"pseudolymphoma\" was employed for case identification. Results Among 319 pseudolymphoma reports, 44 were associated with dihydropyridines and 1 with non-dihydropyridines. Amlodipine demonstrated the strongest signal (ROR 38.08, 95% CI 27.60-52.54; n=42), followed by nifedipine (ROR 18.61, 95% CI 4.64-74.74; n=2). Diltiazem showed a non-significant signal (ROR 5.47, 95% CI 0.77-38.93; n=1). Felodipine and verapamil yielded no reports. Dihydropyridines exhibited 7- to 70-fold greater reporting odds ratios compared with non-dihydropyridines. Conclusions This analysis establishes a robust, though not causal, class-specific safety signal linking dihydropyridine CCBs, particularly amlodipine, to pseudolymphoma risk. The substantial disproportionality suggests a pharmacologically mediated mechanism requiring heightened clinical surveillance, prompt recognition, and timely drug discontinuation to prevent potential malignant transformation.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834070","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

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 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-05-04 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":"https://doi.org/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, 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 (1,833 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":""},"PeriodicalIF":1.3,"publicationDate":"2026-05-04","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

Cost-Effectiveness of Incretin Therapies: A Canadian Lens on Diabetes, Obesity, and Emerging Indications. 肠促胰岛素治疗的成本-效果：加拿大对糖尿病、肥胖和新出现适应症的观察。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-04-21 DOI: 10.1139/cjpp-2025-0248

Luke Awadalla, Siena Iskander, Cherry Chu, Mina Tadrous

引用次数: 0

Cerebral Edema and Brain Death Following Intravenous N-Acetylcysteine Overdose: A Case Report. 静脉注射过量n -乙酰半胱氨酸后脑水肿和脑死亡1例报告。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-04-21 DOI: 10.1139/cjpp-2025-0341

Riley James Hartmann, Sunil Pradhan, Diana Bylyku, Kristine Markieta, James Scozzafava, Scott Lucyk, Mark Yarema

{"title":"Cerebral Edema and Brain Death Following Intravenous N-Acetylcysteine Overdose: A Case Report.","authors":"Riley James Hartmann, Sunil Pradhan, Diana Bylyku, Kristine Markieta, James Scozzafava, Scott Lucyk, Mark Yarema","doi":"10.1139/cjpp-2025-0341","DOIUrl":"https://doi.org/10.1139/cjpp-2025-0341","url":null,"abstract":"N-acetylcysteine (NAC) infusions are rarely associated with cerebral edema. We present a patient that received 1242.2 mg/kg intravenous NAC over 8.3 hours who developed seizures, cerebral edema, and died. A 17-24 year-old female (48.3 kg) presented after an acute acetaminophen ingestion. Their initial presumed five-hour acetaminophen concentration was 591.7 umol/L. Initial ALT and AST were 16 and 21 IU/L, respectively. Due to inconsistencies in the time of ingestion, IV NAC was initiated as a two-step protocol of 150 mg/kg over one hour followed by 15 mg/kg/hr for 20 hours. During treatment, the patient developed vomiting, flushing, and a maculopapular rash. It was discovered that NAC had been administered continuously at 150 mg/kg/hr for 8.3 hours and was stopped. The patient became confused and agitated, and subsequently developed seizures. They were treated with lorazepam, phenytoin, intubation, and propofol. Neuroimaging demonstrated cerebral edema with cerebellar tonsillar herniation. Despite neurocritical care, the patient died 86 hours post-ingestion. The patient's ALT and AST remained normal. Investigations including lumbar puncture and post-mortem toxicology analysis was unremarkable. Clinicians must be aware of the clinical features of supratherapeutic IV NAC dosing errors and potential adverse effects.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763334","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

Different responses to homocysteine in primary endothelial cells and 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 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-07 DOI: 10.1139/cjpp-2025-0250

Zuzana Matiko, Roman Moravčík, Michal Zeman

{"title":"Different responses to homocysteine in primary endothelial cells and immortalized endothelial cell line.","authors":"Zuzana Matiko, Roman Moravčík, Michal Zeman","doi":"10.1139/cjpp-2025-0250","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":1.3,"publicationDate":"2026-01-07","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

Endoplasmic reticulum stress, calcium homeostasis, and the aging heart. 内质网应激、钙稳态与心脏老化。

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-2025-0190

Izabela Quest, Marek Michalak

引用次数: 0

Ameliorative effect of roxithromycin against prostate inflammation-induced chronic pelvic pain in a preclinical model. 罗红霉素对前列腺炎引起的慢性盆腔疼痛的改善作用

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0262

Vishnu Prabha P, Prasenjit Das, Sneha Vangaveti, Vijay L Kumar

{"title":"Ameliorative effect of roxithromycin against prostate inflammation-induced chronic pelvic pain in a preclinical model.","authors":"Vishnu Prabha P, Prasenjit Das, Sneha Vangaveti, Vijay L Kumar","doi":"10.1139/cjpp-2025-0262","DOIUrl":"https://doi.org/10.1139/cjpp-2025-0262","url":null,"abstract":"In view of the well-known anti-inflammatory property of roxithromycin, the present study was carried out to evaluate its efficacy in ameliorating prostate inflammation-induced chronic pelvic pain in rat model. Inflammation was induced by single intraprostatic injection of carrageenan where a time course study revealed a peak histology score on day 14. The efficacy study was carried out in four sets of rats, each comprising five groups, which included respective normal and experimental controls (NC, EC). The drugs (roxithromycin 5 and 20 mg/kg, diclofenac 5 mg/kg) were given daily orally and pain score and body weight were evaluated at different time intervals. The prostatic index, vascular permeability, tissue levels of TNF-α and PGE2, thiobarbituric acid reactive substances, glutathione and superoxide dismutase, histology score, and immunoreactivity of COX-2 and iNOS were evaluated on day 14. Like diclofenac, roxithromycin decreased pain score and the rats gained weight during the study period as compared to the EC group. The beneficial effect of roxithromycin was also evident from the dose-dependent restoration of markers of inflammation and oxidative stress. This study shows that by alleviating pain and suppressing inflammation and oxidative stress, roxithromycin has a potential to provide relief in prostatitis.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":"104 ","pages":"1-9"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670535","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

Assessment of human placental microbial signatures in pre-eclampsia using shotgun metagenomics. 使用散弹枪宏基因组学评估子痫前期人类胎盘微生物特征。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0274

Kehinde Samuel Olaniyi, Jagidesa Moodley, Roshila Moodley, Irene Mackraj

{"title":"Assessment of human placental microbial signatures in pre-eclampsia using shotgun metagenomics.","authors":"Kehinde Samuel Olaniyi, Jagidesa Moodley, Roshila Moodley, Irene Mackraj","doi":"10.1139/cjpp-2025-0274","DOIUrl":"10.1139/cjpp-2025-0274","url":null,"abstract":"This study evaluated the presence of bacterial species in the placenta of women with pre-eclampsia and compared with that of normotensive women. One hundred and twenty participants, comprising 60 pre-eclamptic (30 early- and late-onset, respectively) and 60 age-matched normotensive women (30 early and late-gestation normotensive, respectively) were recruited. After informed consent was obtained, the placenta were obtained through caesarean section with sterile and standardized clinical procedures. DNA was extracted from each tissue, and the samples were pooled into six libraries and sequenced on Illumina NextSeq500 using a shotgun metagenomic approach. Bioinformatics was used to analyse the reads with the implementation of Kraken2/MetaPhlAn classification methods and complemented by multi-layered contamination assessment strategy that included frequency-based decontam filtering. Most reads were classified as belonging to the phyla Cutibacterium acnes, Staphylococcus epidermidis, and various Bradyrhizobium species. PE samples showed notable Corynebacterium tuberculostearicum and Pseudomonas species, while Bradyrhizobium and Cutibacterium acnes dominated normotensive samples. Further analysis showed no significant difference between bacterial species of pre-eclamptic and normotensive placental samples. The results show very low levels of bacteria in the placental samples. In addition, a little difference was observed between the bacterial compositions of pre-eclamptic and age-matched normotensive placental tissues, but not statistically significant.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-11"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194101","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

Deferoxamine alleviates brain ischemia/reperfusion injury through decreasing LAG-3 and α-Syn expression. 去铁胺通过降低LAG-3和α-Syn的表达减轻脑缺血再灌注损伤。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0114

Amany Mansour, Mahmoud R Abdel-Fadeil, Ahmed Shoyb Mohamed, Rasha Mohamed Samir Sayed, Asmaa A Muhammed

{"title":"Deferoxamine alleviates brain ischemia/reperfusion injury through decreasing LAG-3 and α-Syn expression.","authors":"Amany Mansour, Mahmoud R Abdel-Fadeil, Ahmed Shoyb Mohamed, Rasha Mohamed Samir Sayed, Asmaa A Muhammed","doi":"10.1139/cjpp-2025-0114","DOIUrl":"10.1139/cjpp-2025-0114","url":null,"abstract":"Ischemic stroke is characterized by brain tissue iron accumulation. Alpha-synuclein (α-Syn) is a neuronal protein, its overexpression in ischemic stroke triggers apoptosis. Lymphocyte activation gene-3 (LAG-3), a receptor for α-Syn, enhances its neurotoxic effects. It is split from the cell membrane forming soluble LAG-3 (sLAG-3) in the bloodstream. The expression of LAG-3 in the brain, its relation to iron and α-Syn, as well as the association between serum sLAG-3 levels, iron, α-Syn, and stroke severity remains poorly understood. A case-control study was generated involving 24 patients with acute ischemic stroke and 24 healthy controls. In addition, an experimental study was designed involving 24 Wistar-albino rats. We randomly assigned rats to three groups: sham-operated, brain ischemia, and deferoxamine-treated ischemic rats. Ischemia decreased serum levels of iron, while increased serum levels of α-Syn and sLAG-3. Significant diagnostic performance of serum α-Syn and sLAG-3 was determined using the ROC curve (AUC = 0.962, 83.33% sensitivity, and 95.83% specificity for α-Syn; AUC = 0.755 with 62.50% sensitivity and 87.50% specificity for LAG-3). In rats, ischemia elevated brain tissue iron, α-Syn, and LAG-3 which were reduced following deferoxamine treatment. In conclusion, brain ischemia is associated with iron accumulation that promotes α-Syn expression and aggregation, potentially through increasing LAG-3 expression which improved after deferoxamine injection. In addition, this study illuminates the future beneficial targeting of LAG-3 in brain ischemia.","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":"145660458","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

Sex-specific effects of abdominal aortic constriction on renal cytochrome P450 enzymes and arachidonic acid metabolites in male and female rats. 腹主动脉收缩对雌雄大鼠肾细胞色素P450酶和花生四烯酸代谢物的性别特异性影响。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 Epub Date: 2025-12-16 DOI: 10.1139/cjpp-2025-0157

Samar H Gerges, Sara A Helal, Heidi L Silver, Jason R B Dyck, Ayman O S El-Kadi

{"title":"Sex-specific effects of abdominal aortic constriction on renal cytochrome P450 enzymes and arachidonic acid metabolites in male and female rats.","authors":"Samar H Gerges, Sara A Helal, Heidi L Silver, Jason R B Dyck, Ayman O S El-Kadi","doi":"10.1139/cjpp-2025-0157","DOIUrl":"10.1139/cjpp-2025-0157","url":null,"abstract":"We previously showed that male rats develop more severe cardiac hypertrophy than female rats following abdominal aortic constriction (AAC) and highlighted corresponding changes in cardiac cytochrome P450 (CYP) enzymes and their arachidonic acid (AA) metabolites. In this study, we report sex-specific changes in renal CYP enzymes and AA metabolites after AAC. Kidneys were isolated from adult male and female Sprague-Dawley rats 5 weeks after sham or AAC surgeries. Renal CYP, lipoxygenase, and epoxide hydrolase enzyme levels were measured by PCR and Western blot, and renal microsomal formation of hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) was measured by liquid chromatography-tandem mass spectrometry. Protein levels of CYP2E1 and CYP4F were significantly elevated post-AAC only in female rats, paralleled by a significant increase in their respective metabolites, 19(R)-HETE and 20-HETE. On the other hand, CYP2C23 mRNA levels were significantly decreased only in male rats, with no significant decrease in EETs. Our findings indicate that renal CYP-mediated AA metabolism undergoes sex-specific reprogramming in response to cardiac pressure overload, which may contribute to the observed divergent cardiac remodeling. This research highlights the importance of the kidney-heart axis and supports the potential for sex-specific metabolic targets in the treatment of cardiovascular diseases.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-16"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502222","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