Nunes T, Nygard K, Courchesne M
… +3 more, Whitehead S, Richardson B, Regnault TRH
Can J Physiol Pharmacol
· 2025 May · PMID 40243505
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Fetal growth restriction is implicated in the programming of later-life neurodegeneration. We hypothesized that growth-restricted offspring would show accelerated changes to microglial white matter morphology, relative t...Fetal growth restriction is implicated in the programming of later-life neurodegeneration. We hypothesized that growth-restricted offspring would show accelerated changes to microglial white matter morphology, relative to controls. Control guinea pig sows were fed ad libitum, while maternal nutrient restriction sows received 70% of control diet switched to 90% from mid-gestation. Offspring were sacrificed at ∼26 days (neonate) or ∼110 days (adult) postpartum. Coronal brain sections from the frontal cortex were subject to IBA1 staining for microglial detection and analyzed by machine learning software. At birth, total body weight of growth-restricted offspring was reduced relative to control ( < 0.0001) with postnatal catch-up growth observed. Microglial density was reduced in the corpus callosum of control ( < 0.05) and growth-restricted ( = 0.13) adults, relative to neonates. Adults from both groups showed greater IBA1-positive area in the cingulum and periventricular white matter ( < 0.05) and increased microglial fractal dimension in the corpus callosum ( < 0.10) and periventricular white matter ( < 0.05), relative to neonates. At the time points studied, we report age-related changes in white matter microglial morphology. However, maternal nutrient restriction leading to fetal growth restriction in guinea pigs does not appear to exacerbate these white matter microglia morphological changes as a marker for later-life neurodegeneration.
NAD is an important cofactor involved in regulating many biochemical processes in cells. An imbalance in NAD/NADH ratio is linked to many diseases. NAD is depleted in diabetes, cardiovascular and neurodegenerative diseas...NAD is an important cofactor involved in regulating many biochemical processes in cells. An imbalance in NAD/NADH ratio is linked to many diseases. NAD is depleted in diabetes, cardiovascular and neurodegenerative diseases, and in aging, and is increased in tumor cells. NAD is generated in cells via the de novo, Preiss-Handler, and salvage pathways. Most of the cellular NAD is generated through Nampt activation, a key rate-limiting enzyme that is involved in the salvage pathway. Restoration of NAD/NADH balance offers therapeutic advantages for improving tissue homeostasis and function. NAD is known to benefit and restore the body's physiological mechanisms, including DNA replication, chromatin and epigenetic modifications, and gene expression. Recent studies elucidate the role of NAD in cells utilizing transgenic mouse models. Translational new therapeutics are positioned to utilize the NAD restoration strategies for overcoming the drawbacks that exist in the pharmacological toolkit. The present review highlights the significance of Nampt-NAD axis as a major player in energy metabolism and provides an overview with insights into future strategies, providing pharmacological advantages to address current and future medical needs.
The lack of polygenic scores (PGSs) developed for body mass index (BMI) in children may be problematic because the genetic architecture characterizing BMI changes throughout life. This study aims to describe the genetic...The lack of polygenic scores (PGSs) developed for body mass index (BMI) in children may be problematic because the genetic architecture characterizing BMI changes throughout life. This study aims to describe the genetic susceptibility to obesity in children and to compare two PGSs based on data from adults and children and their association with BMI and discrimination of obesity. The study sample comprises 717 participants aged 4-13 years. Adult- and child-based PGSs were evaluated by examining (1) mean BMI across polygenic score risk categories, (2) the capacity to identify obesity with logistic regression, and (3) the linear association with BMI z-scores using linear regression. Increases in one standardized unit of adult-based PGS were related to a stronger increase in BMI z-score (β = 0.24-0.39) than PGS derived in children (β = 0.21-0.30). The association between obesity and the child score was higher (OR = 1.75-2.33) than that for the adult score (OR = 1.74-2.06) for the age group 4-7 years. The inverse was observed for the age group 8-13 years (OR 1.56-1.79 vs. OR 1.78-2.54). Both adult- and child-based PGSs show strong associations with BMI and risk of obesity, with the adult-based score standing out from 8 years old.
Pop A, Dănilă M, Giuchici S
… +5 more, Buriman D, Lolescu B, Sturza A, Muntean D, Lascu A
Can J Physiol Pharmacol
· 2025 May · PMID 40048723
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The epicardial adipose tissue (EAT) serves in physiological conditions as a mechanical and thermal myocardial protective layer, as well as a readily available lipid-storage unit. In pathological conditions, EAT expansion...The epicardial adipose tissue (EAT) serves in physiological conditions as a mechanical and thermal myocardial protective layer, as well as a readily available lipid-storage unit. In pathological conditions, EAT expansion becomes deleterious and is currently recognized as an independent risk factor for the progression of cardiovascular diseases. The EAT phenotypic shift from protective to pro-inflammatory/pro-oxidant is facilitated by the presence of metabolic diseases (obesity, metabolic syndrome, and diabetes), which further increase its expansion and dysregulation, favor the occurrence of complications (mainly atrial fibrillation), and promote progression towards heart failure. Glucagon-like peptide-1 (GLP-1) receptor agonists are novel antidiabetic medications belonging to the incretin class that have demonstrated efficacy beyond glycemic control, in terms of weight reduction and cardiorenal protection in patients with type 2 diabetes mellitus. The GLP-1 receptors and glucose-dependent insulinotropic polypeptide (GIP) receptors are expressed in the human EAT and are targeted by an increasing number of pharmacological agonists, with pleiotropic protective effects on EAT structure and function. Herein we review the literature characterizing the benefits of GLP-1 and GIP receptors activation by single and dual agonists with particular emphasis on their effects on EAT and highlight the role of incretin-based therapy for the management of cardiometabolic pathologies.
Diab A, Stack H, McKeown B
… +2 more, Carleton B, Goralski KB
Can J Physiol Pharmacol
· 2025 May · PMID 40048722
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In response to the COVID-19 pandemic, Canadian clinical researchers pivoted their research programs to investigate repurposing drugs, accelerating the development of experimental therapies, and developing novel disease-s...In response to the COVID-19 pandemic, Canadian clinical researchers pivoted their research programs to investigate repurposing drugs, accelerating the development of experimental therapies, and developing novel disease-specific treatments. This systematic review analyzes the trial design, participant characteristics, and reported outcomes of all Health Canada authorized clinical trials of therapeutics to prevent or treat COVID-19 with published results as of March 2023. We conclude that there is a need for adaptive clinical trial designs, broader pan-Canadian clinical trial networks, more targeted participant recruitment to facilitate increased diversity and inclusion, and standardization in reporting participant characteristics, outcome measurement, and follow-up. Finally, guided by our findings, we make recommendations for improved clinical trial designs when faced with an emerging disease.
Can J Physiol Pharmacol
· 2025 May · PMID 39999429
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Doxorubicin is a commonly used chemotherapy that rapidly accumulates in skeletal muscle and disrupts nitric oxide (NO) formation. However, studies investigating these effects have largely been performed in tumour-free mo...Doxorubicin is a commonly used chemotherapy that rapidly accumulates in skeletal muscle and disrupts nitric oxide (NO) formation. However, studies investigating these effects have largely been performed in tumour-free models, therefore it remains unknown whether intramuscular accumulation and disruptions to NO content persist during tumour growth. Female C57bl/6 mice ( = 8/group) were randomly assigned to true control, doxorubicin control, tumour only, or tumour plus doxorubicin groups. Tumours were grown for 21, 24, or 28 days using E0771 cells. Doxorubicin was administered as a single 10 mg/kg intraperitoneal dose on day 21. Doxorubicin accumulation was similar in muscle with and without tumours present. Doxorubicinol, a metabolite of doxorubicin, was elevated ( < 0.05) in 24-day tumour + doxorubicin compared to doxorubicin alone. NO was similar across all groups in muscle; however, tumour NO was 15-fold higher at day 21 compared to 24, or 28 days ( < 0.05). The results confirm that doxorubicin is sequestered in skeletal muscle when a tumour is present, which may impact bioavailability. Tumour growth transiently increased intramuscular doxorubicinol, potentially exacerbating the toxicity of the drug. Earlier stage tumour growth appeared to profoundly elevate NO, which could suggest temporal angiogenesis and vasodilation to facilitate growth.
Corbin S, Lavallée M, Pradhan P
… +9 more, Thibault M, Méthot J, Djiokeng L, Bérard A, Piché M, Gimenes F, Darveau R, Cloutier I, Leclerc J
Can J Physiol Pharmacol
· 2025 May · PMID 39983100
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Adverse events among drug users are frequent during hospital stay. Causality assessment of adverse events was poorly documented by healthcare professionals in a hospital setting.Adverse events among drug users are frequent during hospital stay. Causality assessment of adverse events was poorly documented by healthcare professionals in a hospital setting.
Striatal medium spiny neurons (MSN) form two subpopulations (MSN-D and MSN-D) according to the expression of dopamine D or D receptors and their target regions. The activation of postsynaptic histamine H and H receptors...Striatal medium spiny neurons (MSN) form two subpopulations (MSN-D and MSN-D) according to the expression of dopamine D or D receptors and their target regions. The activation of postsynaptic histamine H and H receptors increases MSN-D and MSN-D excitability. Since MSN also express H receptors (HRs), in this work we explored the effect of their activation on MSN firing. Electrophysiological recordings (whole-cell patch-clamp, current-clamp mode) were conducted on forebrain slices from infantile rats (12-16 postnatal days). In both MSN-D and MSN-D perfusion with the HR agonist immepip (1 µmol/L) increased neuronal firing evoked by current injection, an effect reproduced by R-α-methylhistamine (1 µmol/L) and prevented by the antagonist clobenpropit (10 µmol/L). Blockade of N- or P/Q-type voltage-activated calcium channels by ω-conotoxin-GVIA (1 µmol/L) or ω-agatoxin-TK (400 nmol/L) increased MSN firing but did not preclude the immepip effect. The potassium channel blockers 4-aminopyridine (1 mmol/L) and tetraethylammonium (300 µmol/L) increased neuronal firing and prevented the immepip action. Likewise, the K7 channel blocker XE-991 (10 µmol/L) and the muscarinic receptor agonist carbachol (10 µmol/L) increased MSN firing frequency and occluded the immepip effect. These data indicate that the activation of postsynaptic HRs facilitates MSN-D and MSN-D firing by inhibiting K7 potassium channels.
Filho A, Akolkar G, Lima L
… +6 more, Stoyell-Conti F, Bernardes N, Irigoyen M, Singal P, De Angelis K, Dias DS
Can J Physiol Pharmacol
· 2025 May · PMID 39938071
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Doxorubicin is known for its significant cardiotoxicity, in part due to increased oxidative stress (OS). In addition, preclinical models have shown that doxorubicin induces skeletal muscle atrophy. While vitamin C has be...Doxorubicin is known for its significant cardiotoxicity, in part due to increased oxidative stress (OS). In addition, preclinical models have shown that doxorubicin induces skeletal muscle atrophy. While vitamin C has been recognized as a valuable pharmacological intervention to mitigate cardiac toxicity, its effect on doxorubicin-induced skeletal muscle atrophy remains to be determined. Therefore, the aim of this study was to investigate the effects of vitamin C on skeletal muscle of rats exposed to doxorubicin. Indeed, doxorubicin caused a reduction in body weight and gastrocnemius muscle weight, accompanied by an increase in hydrogen peroxide, protein oxidation, and lipid peroxidation in the gastrocnemius muscle. On the other hand, vitamin C was able to prevent the loss of skeletal muscle mass as well as the increase in markers of OS. In addition, negative correlations were found between gastrocnemius muscle mass and markers of cellular damage. In conclusion, vitamin C appears to be a protective agent against doxorubicin-induced skeletal muscle atrophy and OS. This suggests its potential application as a prophylactic measure for patients undergoing doxorubicin treatment.
The growing epidemic of opioid misuse presents numerous challenges for healthcare practitioners and patients alike as friction exists between ease of use and efficacy, and potential for overuse and addiction. With over 8...The growing epidemic of opioid misuse presents numerous challenges for healthcare practitioners and patients alike as friction exists between ease of use and efficacy, and potential for overuse and addiction. With over 82 000 deaths related to opioid overdose in North America in 2020, it is imperative to gain a better understanding of the underlying mechanisms behind the addiction process, as well as the current methods being used in the arsenal against this disease. The current best pharmacological approaches for mediating opioid use disorder are methadone, buprenorphine, naltrexone, and naloxone, which act on opioid receptors to produce diverse effects based upon the patients' needs. The variety of effects that these drugs produce, which include removing opioid withdrawal, reversing overdose effects, and blocking opioid properties, makes this arsenal of therapeutics a global necessity in addressing the opioid use epidemic. Accordingly, this narrative review provides a summary of the available data regarding the physiological processes by which opioid addiction takes place and discusses the current and future potential of interventional methods used to mitigate opioid use disorder. The mechanisms of action and subsequent functional outcomes must be understood to reduce the number of opioid-related deaths worldwide.
Can J Physiol Pharmacol
· 2025 Oct · PMID 39919269
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As our understanding of acute coronary syndromes (ACS) has increased, we have been able to better delineate the unique pathologies that cause ACS. This review article on the common causes of ACS in females explores the a...As our understanding of acute coronary syndromes (ACS) has increased, we have been able to better delineate the unique pathologies that cause ACS. This review article on the common causes of ACS in females explores the atherosclerotic pathologies of plaque rupture and plaque erosion, and non-atherosclerotic pathologies of SCAD, MINOCA, and Takotsubo cardiomyopathy. It reviews the literature on the link between estrogen and its protection against both atherosclerotic risk factors and induction of plaque vulnerability. This review also explores the mechanistic plausibility that estrogen may contribute to the increased risk of SCAD, MINOCA, and Takotsubo cardiomyopathy-although these mechanisms remain under investigation. Whilst there is still much to be researched about these pathologies, an analysis of the biological impact of sex hormones at the molecular level has helped identify links between mechanisms suggesting a possible unifying pathology between plaque erosion, MINOCA, and microvascular spasm. In this way, a new paradigm for ACS as an equilibrium between thrombus-stabilisation and thrombus-dissolution states is also explored in this article. What has become evident is that the attempt to understand the common causes of ACS in females has resulted also in a deeper understanding of atherosclerotic ACS in males, and highlighted areas of exciting further discovery.
Kesavan K, Panchakshari S, Abdelwahab H
… +2 more, Rabelo E, Chaudhary KR
Can J Physiol Pharmacol
· 2025 Mar · PMID 39841976
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A growing body of evidence suggest that the stem cell antigen-1 expressing (Sca-1) cells in the heart may be the cardiac endothelial stem/progenitor cells. Their endothelial cell (EC) functions, and their role in right v...A growing body of evidence suggest that the stem cell antigen-1 expressing (Sca-1) cells in the heart may be the cardiac endothelial stem/progenitor cells. Their endothelial cell (EC) functions, and their role in right ventricle (RV) physiology and pathophysiology of right heart failure (RHF) remains poorly defined. This study investigated EC characteristics of rat cardiac Sca-1 cells, assessed spatial distribution and studied changes in Sca-1 cells during RV remodelling in monocrotaline (MCT) model of pulmonary hypertension and RV remodeling. First, flow-cytometry analysis of adult male and female Sprague Dawley (SD) and Fischer CDF rat heart cells was performed, and we observed that the majority of Sca-1 cells also expressed CD31, an EC marker. Furthermore, Sca-1 cells showed acetylated low-density lipoprotein (ac-LDL) uptake and lectin binding similar to CD31 cells from the same heart. The Sca-1 cells also demonstrated network formation when plated on Matrigel. In the MCT treated rats, we observed increase in RV hypertrophy that correlated with the reduction in the abundance of Sca-1CD31 cells in the RV. Together, the cardiac Sca-1 cells in the heart are endothelial stem/progenitor-like cells. These cells have higher abundance in the RV and may play a role in RV adaptation.
Aerobic exercise (AE) is associated with a significant hypoglycemia risk in individuals with type 1 diabetes mellitus (T1DM). However, the mechanisms in the liver and skeletal muscle governing exercise-induced hypoglycem...Aerobic exercise (AE) is associated with a significant hypoglycemia risk in individuals with type 1 diabetes mellitus (T1DM). However, the mechanisms in the liver and skeletal muscle governing exercise-induced hypoglycemia in T1DM are poorly understood. This study examined the effects of a 60-min bout of AE on hepatic and muscle glucose metabolism in T1DM rats. Nineteen male Sprague-Dawley rats were divided into sedentary (SC; = 5) and T1DM (DSC; = 14) groups. T1DM rats were subcategorized into pre-exercise (DPRE; = 6) and post-exercise (DPOST; = 8). DPOST were sacrificed immediately after 60 min of AE. Results demonstrate that DPOST animals experienced reductions in BG following 30 and 60 min of AE compared to pre-exercise. Both DPRE and DPOST animals exhibited lower hepatic glycogen content, while muscle glycogen did not differ, suggesting impaired glycogenolysis in T1DM. Hepatic glucose-6-phosphatase content, and muscle and hepatic protein kinase B phosphorylation were significantly greater in DPOST animals, suggesting elevated gluconeogenesis and insulin stimulation during exercise. Glycogen phosphorylase activity did not differ between groups. These data suggest that drops in BG during AE in T1DM were due to lower glycogen levels in the liver and muscle and a lack of muscle glycogen utilization; leading to a reliance on gluconeogenesis and BG.
Polson S, Thornburg J, McNair B
… +6 more, Cook C, Straight E, Fontana K, Hoopes C, Nair S, Bruns DR
Can J Physiol Pharmacol
· 2025 Mar · PMID 39693609
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Diabetic cardiomyopathy (DCM) is a growing clinical entity and major health burden characterized by comorbid diabetes mellitus and heart failure. DCM has been commonly associated with impaired function of the left ventri...Diabetic cardiomyopathy (DCM) is a growing clinical entity and major health burden characterized by comorbid diabetes mellitus and heart failure. DCM has been commonly associated with impaired function of the left ventricle (LV); however, DCM likely also occurs in the right ventricle (RV) which has distinct physiology and pathophysiology from the LV. RV dysfunction is the strongest determinant of mortality in several clinical contexts yet remains poorly studied in diabetes. We investigated RV-specific pathophysiology using two models of diabetes-a well-characterized type 2 diabetes (T2DM) model of high-fat diet and low-dose streptozotocin (STZ) in the mouse and a large animal model of type I diabetes in domestic pigs rendered diabetic with STZ. RV global and systolic function deteriorated with diabetes, alongside hypertrophic and fibrotic remodeling. We report evidence of impaired RV insulin sensitivity, dysregulated RV metabolic gene expression, and impaired mitochondrial dynamics. Importantly, while some of these outcomes were similar to those widely reported in the LV, others were not, such as unchanged antioxidant gene expression and regulators of fatty acid uptake. Importantly, these RV-specific changes occurred in both male and female T2DM mice, together emphasizing the importance of distinguishing the RV from the LV when studying DCM and begging the consideration of RV-specific therapies.
Han W, Morris R, Bu K
… +3 more, Zhu T, Huang H, Cheng F
Can J Physiol Pharmacol
· 2025 Feb · PMID 39620731
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The FDA Adverse Event Reporting System (FAERS) is a large-scale repository of reports concerning adverse drug events (ADEs). The same published clinical study or report may be reviewed by multiple companies or healthcare...The FDA Adverse Event Reporting System (FAERS) is a large-scale repository of reports concerning adverse drug events (ADEs). The same published clinical study or report may be reviewed by multiple companies or healthcare professionals and reported separately to the FDA, leading to a significant presence of duplicate reports in FAERS. These duplicate records can result in the identification of false associations between a given drug and an ADE. In this study, we first assessed the consistency of drug and ADE information in FAERS reports from Alzheimer's disease patients. Our findings showed greater congruence in drug-related information compared to ADE-related information, likely due to the greater heterogeneity and variety of terms or phrases used to describe ADEs. We then demonstrated that text comparison methods are effective in identifying duplicate records based on literature citations, testing 10 different comparison functions for their overall efficacy. Token-based methods (such as COSINE, QGRAM, and JACCARD), edit-based approaches (including OSA, LV, and DL), and sequence-based techniques like LCS have proven highly effective in accurately detecting identical publications within free text, demonstrating both high sensitivity and specificity. These results offer valuable insights for identifying duplicate FAERS reports and improving the reliability of detected associations between drugs and ADEs.
Marijanovic GV, Stojanovic AZ, Nikolic MR
… +2 more, Jakovljevic VLJ, Vulovic TV
Can J Physiol Pharmacol
· 2025 Feb · PMID 39586069
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This study aimed to examine the effect of thiopental monotherapy as well as its combination with different agents used in anesthesia induction, on cardiac function and redox state of rats with type 1 diabetes mellitus (T...This study aimed to examine the effect of thiopental monotherapy as well as its combination with different agents used in anesthesia induction, on cardiac function and redox state of rats with type 1 diabetes mellitus (T1DM). A total of 40 male rats were used in this study and randomly divided into five groups: thiopental (TIO), fentanyl + thiopental (FEN + TIO), remifentanil + thiopental (REM + TIO), midazolam + thiopental (MID + TIO), and dexmedetomidine + thiopental (DEX + TIO). Animals were anesthetized by intraperitoneal injection of thiopental 85 mg/kg, fentanyl 0.005 mg/kg, remifentanil 0.04 mg/kg, midazolam 2.5 mg/kg, and dexmedetomidine 0.05 mg/kg of body weight. Four weeks after T1DM induction, all animals were subjected to a short narcosis of tested anesthetic, sacrificed by cervical dislocation and the hearts were retrogradely perfused according to Langendorff technique. Our research demonstrated that most combined anesthetics negatively influenced cardiodynamic parameters and redox state in diabetic rats. However, significantly improved cardiac contractility associated with enhanced antioxidative capacity was achieved in the combination of TIO with REM, which distinguishes this anesthetic combination as the therapy with the most pronounced positive effect on cardiac function in state of T1DM.
Kahlon S, Sleet M, Sujka J
… +4 more, Docimo S, DuCoin C, Dimou F, Mhaskar R
Can J Physiol Pharmacol
· 2025 Feb · PMID 39561352
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Integrating artificial intelligence (AI) into healthcare prompts the need to measure its proficiency relative to human experts. This study evaluates the proficiency of ChatGPT, an OpenAI language model, in offering guida...Integrating artificial intelligence (AI) into healthcare prompts the need to measure its proficiency relative to human experts. This study evaluates the proficiency of ChatGPT, an OpenAI language model, in offering guidance concerning bariatric surgery compared to bariatric surgeons. Five clinical scenarios representative of diverse bariatric surgery situations were given to American Society for Metabolic and Bariatric Surgery (ASMBS)-accredited bariatric surgeons and ChatGPT. Both groups proposed medical or surgical management for the patients depicted in each scenario. The outcomes from both the surgeons and ChatGPT were examined and matched with the clinical benchmarks set by the ASMBS. There was a high degree of agreement between ChatGPT and physicians on the three simpler clinical scenarios. There was a positive correlation between physicians' and ChatGPT answers for not recommending surgery. ChatGPT's advice aligned with ASMBS guidelines 60% of the time, in contrast to bariatric surgeons, who consistently aligned with the guidelines 100% of the time. ChatGPT showcases potential in offering guidance on bariatric surgery, but it does not have the comprehensive and personalized perspective that doctors exhibit consistently. Enhancing AI's training on intricate patient situations will bolster its role in the medical field.
Can J Physiol Pharmacol
· 2025 Jan · PMID 39481122
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Jadomycin B, a natural product isolated from , exerts an anti-cancer effect on human triple negative breast cancer cells in vitro and has anti-tumoral effects in vivo in animal models of breast cancer. One proposed mecha...Jadomycin B, a natural product isolated from , exerts an anti-cancer effect on human triple negative breast cancer cells in vitro and has anti-tumoral effects in vivo in animal models of breast cancer. One proposed mechanism for this anti-cancer effect is through interaction with topoisomerase 2 (TOP2). Based on the previously described interactions between jadomycin B and TOP2 we hypothesized that jadomycin B will act additively with TOP2 poisons and produce a similar functional outcome in eliciting cell cycle arrest. Combined treatments of jadomycin B and the TOP2 poisons doxorubicin or mitoxantrone produced moderately synergistic to additive cytotoxicity (combination index values ranging from 0.72-0.94) in MDA-MB-231 cells. In comparison, combined mitoxantrone and doxorubicin produced additive cytotoxicity (combination index values 0.96-1.11). Jadomycin B combined with the proteosome inhibitor MG132 had additive cytotoxicity (combination index values 0.76-1.18). In contrast, mitoxantrone or doxorubicin cytotoxicity was antagonized by MG132 (combination index values 1.21-2.31). Jadomycin B treatment arrested cells in S-phase ( = 0.0024) as opposed to mitoxantrone which caused G/M-phase arrest ( < 0.0001). In conclusion, jadomycin B interacts differently than known TOP2 poisons in combination, supporting a novel pharmacological mechanism(s) of action for jadomycin B cytotoxicity.
Sharma P, Varghese Gupta S, Bhatt P
… +4 more, Kandukuru A, Cheng F, Upadhyay G, Sutariya V
Can J Physiol Pharmacol
· 2024 Dec · PMID 39435747
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The purpose of this study was to determine the relationship between triptans (sumatriptan, rizatriptan, and zolmitriptan) and cardiovascular (CV) adverse events with data from the FDA Adverse Event Reporting System (FAER...The purpose of this study was to determine the relationship between triptans (sumatriptan, rizatriptan, and zolmitriptan) and cardiovascular (CV) adverse events with data from the FDA Adverse Event Reporting System (FAERS). FAERS database was used to collect data on triptans from 1997 to 2023. Disproportionality methods were utilized to quantify triptan-associated CV events and to identify the potential risk. The reporting odds ratio was used to identify the risk signals. CV outcomes related to age, sex, clinical results, and other factors were also examined for triptans; 820 reports involving the triptans were recognized as CV adverse events out of total of 12 699 reports that were gathered from on FAERS database. Women reported more CV adverse events with rizatriptan and zolmitriptan as compared to men. The CV adverse event risk was highest among individuals aged 18-64. Clinical outcome analysis showed that sumatriptan carries a higher CV risk than rizatriptan and zolmitriptan, and most deaths and serious cases have been documented for sumatriptan. The patients prescribed sumatriptan or zolmitriptan were at a higher risk of reporting CV events for chest pain and chest discomfort, compared to rizatriptan. This finding may provide support for the clinical observation and risk evaluation of triptan treatment.
Kandukuru A, Sharma P, Verghese Gupta S
… +2 more, Nkembo A, Sutariya V
Can J Physiol Pharmacol
· 2024 Dec · PMID 39431859
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Norepinephrine-dopamine reputake inhibitors (NDRIs), including bupropion, methylphenidate, atomoxetine, and reboxetine, are commonly prescribed for psychiatric disorders such as narcolepsy, attention-deficit/hyperactivit...Norepinephrine-dopamine reputake inhibitors (NDRIs), including bupropion, methylphenidate, atomoxetine, and reboxetine, are commonly prescribed for psychiatric disorders such as narcolepsy, attention-deficit/hyperactivity disorder, and depression. Cardiovascular adverse events have been reported to the FDA despite their effectiveness. This pharmacovigilance study analyzed cardiovascular adverse events associated with NDRIs using the FDA Adverse Event Reporting System data from January 2004 to December 2021. A retrospective analysis of adverse event reports was conducted, employing time-trend analysis and disproportionality evaluation to assess cardiovascular risks. Bupropion had the greatest reported odds ratios (RORs) for tachycardia (ROR = 4.2, 95% CI: 4.0-4.4) and hypertension (ROR = 3.5, 95% CI: 3.3-3.7), while methylphenidate showed greater ROR for arrhythmias (ROR = 2.8, 95% CI: 2.6-3.0) and palpitations (ROR = 3.1, 95% CI: 2.9-3.3). Reboxetine had signals for palpitations (ROR = 3.0, 95% CI: 2.8-3.2) and myocardial infarction (ROR = 2.7, 95% CI: 2.5-2.9), whereas atomoxetine revealed signals for hypertension (ROR = 2.9, 95% CI: 2.7-3.1) and syncope (ROR = 2.5, 95% CI: 2.3-2.7). Time-trend analysis revealed temporal variability in the cardiovascular risks connected with NDRIs. Our research elucidates cardiovascular safety profiles for NDRIs, highlighting the necessity for continuous pharmacovigilance. The observed variations in adverse events emphasize the need for ongoing surveillance to mitigate potential cardiovascular risks and enhance patient safety and treatment outcomes.