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Journal of Nuclear Cardiology :... Jun 2024Myocardial perfusion imaging (MPI) is a powerful tool for the functional assessment of ischemia in patients with suspected or known coronary artery disease (CAD). Given... (Review)
Review
Myocardial perfusion imaging (MPI) is a powerful tool for the functional assessment of ischemia in patients with suspected or known coronary artery disease (CAD). Given that the diagnostic accuracy and prognostic value of MPI and post-test management are highly dependent on achieving an adequate stress vasodilatory response, it is critical to identify those who may not have adequately responded to vasodilator pharmacological stress agents such as adenosine, dipyridamole, and regadenoson. Caffeine, a potent inhibitor of the adenosine receptor, is a compound that can affect vasodilatory hemodynamics, result in false negative studies, and potentially alter management in cases of inaccurate test results. Vasodilator non-responsiveness can be suspected by examining hemodynamics, quantitative positron emission tomography (PET) metrics such as myocardial flow reserve (MFR), and splenic response to stress. Quantitative MFR values of 1-1.2 should raise suspicion for nonresponsiveness in the setting of normal perfusion, along with the absence of a splenic switch off. Newer metrics, such as splenic response ratio, can be used to aid in the identification of potential nonresponders to pharmacologic vasodilators.
Topics: Humans; Vasodilator Agents; Myocardial Perfusion Imaging; Coronary Artery Disease; Exercise Test; Positron-Emission Tomography; Dipyridamole; Coronary Circulation; Adenosine; Purines; Pyrazoles
PubMed: 38518887
DOI: 10.1016/j.nuclcard.2024.101850 -
European Review For Medical and... Mar 2024OBJECTIVE: The primary aim of the present study was to determine the success of single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in...
UNLABELLED
OBJECTIVE: The primary aim of the present study was to determine the success of single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in detecting critical coronary artery disease (CAD) as identified by invasive coronary angiography (ICA), as well as to compare the positive predictive values (PPV) of different stress methods. Our secondary aim was to investigate demographic, laboratory, electrocardiographic, and echocardiographic variables that could predict true positive results. PATIENTS AND METHODS: The study was conducted with 317 consecutive patients. Exercise, dipyridamole, adenosine, or dobutamine were used as stress methods. According to the results of ICA, patients with and without critical CAD were divided into two groups and compared statistically. The independent predictors of true positive results of positive SPECT-MPI were determined using univariate and multivariate logistic regression analysis (MLRA). RESULTS: Among the patients, 129 (40.7%) were found to have critical CAD (+) and 188 (50.3%) critical CAD (-). The PPVs of different stress methods were similar. Age, diabetes, and monocyte to HDL ratio (MHR) were found to be independent predictors of critical CAD in MLRA (p<0.005, p=0.002, and p<0.005, respectively). ROC curve analysis revealed 81.4% sensitivity and 47.3% specificity (AUC: 0.683) at a cut-off of 57 for age and 72.1% sensitivity and 54.3% specificity (AUC: 0.649) for MHR at a cut-off of 9.7. CONCLUSIONS: The true positivity rate of SPECT-MPI is low. Moreover, this rate is much lower for women. The PPVs of different stress methods are similar. Age, presence of diabetes, and MHR ratio are independent predictors for true positive results of SPECT-MPI.
GRAPHICAL ABSTRACT
https://www.europeanreview.org/wp/wp-content/uploads/Graphical-abstract-9.jpg.
Topics: Humans; Female; Aged; Myocardial Perfusion Imaging; Adenosine; Coronary Artery Disease; Dobutamine; Diabetes Mellitus
PubMed: 38497864
DOI: 10.26355/eurrev_202403_35595 -
Hemorrhage induced by antithrombotic agents: new insights from a real-world pharmacovigilance study.Expert Opinion on Drug Safety Apr 2024Hemorrhage represents the most common and serious side effect of antithrombotic agents. Many studies have compared the risk of bleeding between different antithrombotic...
BACKGROUND
Hemorrhage represents the most common and serious side effect of antithrombotic agents. Many studies have compared the risk of bleeding between different antithrombotic agents, but analysis of time-to-onset for hemorrhage induced by these drugs is yet sparse.
METHODS
We conducted a retrospective study based on the adverse drug reaction reports on antithrombotic agents collected by the Henan Adverse Drug Reaction Monitoring Center. We assessed the reporting odds ratio to determine the disproportionate reporting signals for bleeding and the Weibull shape parameter was used to evaluate the time-to-onset data.
RESULTS
In the signal detection, crude low molecular weight heparin-hemorrhage was found as a positive signal. The hemorrhage for most antithrombotic agents was random failure profiles. In particular, the hazard of hemorrhage decreased over time for warfarin and clopidogrel and increased for alteplase, nadroparin, and dipyridamole.
CONCLUSION
We found that the risk of bleeding in patients taking Crude low molecular weight heparins was significantly higher compared to other antithrombotic agents, but with a small magnificence, which may be attributed to the severely irrational use of this medication under improper management. Statistics in days, results showed that the risk of bleeding decreased over time for warfarin and clopidogrel and increased for alteplase, nadroparin, and dipyridamole.
Topics: Humans; Fibrinolytic Agents; Warfarin; Nadroparin; Clopidogrel; Tissue Plasminogen Activator; Retrospective Studies; Pharmacovigilance; Hemorrhage; Anticoagulants; Dipyridamole; Drug-Related Side Effects and Adverse Reactions; Platelet Aggregation Inhibitors
PubMed: 38497691
DOI: 10.1080/14740338.2024.2327502 -
Fundamental & Clinical Pharmacology Mar 2024Adenosinergic system has been implicated in the pathophysiology of bipolar disorder and drugs that affect adenosine neurotransmission have shown some efficacy as add-on...
BACKGROUND
Adenosinergic system has been implicated in the pathophysiology of bipolar disorder and drugs that affect adenosine neurotransmission have shown some efficacy as add-on therapy in manic patients.
OBJECTIVE
Thus, the aim of the present study was to screen adenosinergic drugs for antimanic-like effect in methylphenidate (MPH)-induced hyperlocomotion in mice.
METHODS
Male and female Swiss mice received a single allopurinol (50 and 200 mg/kg, ip), dipyridamole (20 mg/kg, ip), or inosine (50 mg/kg, ip) administration before an acute MPH challenge (5 mg/kg, sc). In experiments with repeated treatment, male mice received a daily administration of allopurinol (25 and 50 mg/kg, ip), dipyridamole (20 mg/kg, ip), or inosine (50 mg/kg, ip) for 14 days. Finally, pretreatment with aminophylline (2 mg/kg, sc), an unspecific adenosine receptor antagonist, was used to evaluate a putative adenosinergic mediation. Locomotor activity was measured in the automated activity chamber for 20 min.
RESULTS
Acute and repeated dipyridamole reduced the increase in locomotor activity induced by MPH, while allopurinol and inosine had no effect. Aminophylline blocked the effect of dipyridamole in MPH-induced hyperlocomotion.
CONCLUSION
The present results suggest that dipyridamole may have an antimanic-like effect through adenosine receptors and reinforce the proposal that the adenosine system may be an interesting target for new antimanic drugs.
PubMed: 38472106
DOI: 10.1111/fcp.13001 -
The International Journal of Biological... Mar 2024To evaluate cytokine and soluble programmed death ligand-1 (sPD-L1) levels in the serum and plasma of cancer patients treated with immunotherapy, and to test different...
AIM
To evaluate cytokine and soluble programmed death ligand-1 (sPD-L1) levels in the serum and plasma of cancer patients treated with immunotherapy, and to test different assays.
METHODS
Three Luminex xMAP assays and two ELLA microfluidic cartridges were used to screen 28 immune-related biomarkers in 38 paired serum and citrate-theophylline-adenosine-dipyridamole (CTAD) plasma samples collected from 10 advanced melanoma or non-small cell lung cancer (NSCLC) patients at different time points during immunotherapy.
RESULTS
Twenty-three of 28 biomarkers were detected both in serum and plasma by at least one of the assays, including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, GM-CSF, IFN-γ, TNF-α, VEGF, IP-10, MCP-1, eotaxin, fractalkine, G-CSF, IFN-α, IL-1RA, IL-13, IL-17A, MIP-1β and sPD-L1. Conversely, FGF-2 and IL-1α were not detected in both matrices; GRO-α factor and EGF were detected only in serum and MIP-1α only in plasma. sPD-L1, MCP-1, IFN-γ, IL-8, MIP-1β and VEGF were, respectively, 1.15-, 1.44-, 1.83-, 2.43-, 2.82-, 6.72-fold higher in serum, whereas IL-10, IL-4, IL-2 and IL-5 were 1.05-, 1.19-, 1.92- and 2.17-fold higher, respectively, in plasma. IP-10 levels were higher in plasma but, as well as for VEGF, the bias serum versus plasma varied depending on the assay used (IP-10: -5.7% to -145%; VEGF: 115% to 165%). No significant differences were found for the remaining nine analyzed cytokines.
CONCLUSION
The cytokine and sPD-L1 levels may differ between serum and plasma samples collected from cancer patients treated with immunotherapy, and the results obtained can be influenced by the different characteristics of the tested assays. The standardization of pre-analytical and analytical procedures is therefore needed for the future implementation of these circulating biomarkers in clinical practice.
Topics: Humans; Cytokines; Interleukin-10; Chemokine CCL4; Carcinoma, Non-Small-Cell Lung; Chemokine CXCL10; Interleukin-2; Interleukin-4; Interleukin-5; Interleukin-8; Ligands; Vascular Endothelial Growth Factor A; Lung Neoplasms; Biomarkers
PubMed: 38407953
DOI: 10.1177/03936155231226234 -
Pharmaceutics Feb 2024Human serum alpha-1-acid glycoprotein (AAG) is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic...
Human serum alpha-1-acid glycoprotein (AAG) is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic substances. The sialic acid groups that terminate the N-glycan chains of AAG have been reported to change in response to numerous health conditions and may have an impact on the binding of drugs to AAG. In this study, we quantified the binding between native and desialylated AAG and seven drugs from different pharmacotherapeutic groups (carvedilol, diltiazem, dipyridamole, imipramine, lidocaine, propranolol, vinblastine) using microscale thermophoresis (MST). This method was chosen due to its robustness and high sensitivity, allowing precise quantification of molecular interactions based on the thermophoretic movement of fluorescent molecules. Detailed glycan analysis of native and desialylated AAG showed over 98% reduction in sialic acid content for the enzymatically desialylated AAG. The MST results indicate that desialylation generally alters the binding affinity between AAG and drugs, leading to either an increase or decrease in values, probably due to conformational changes of AAG caused by the different sialic acid content. This effect is also reflected in an increased denaturation temperature of desialylated AAG. Our findings indicate that desialylation impacts free drug concentrations differently, depending on the binding affinity of the drug with AAG relative to human serum albumin (HSA). For drugs such as dipyridamole, lidocaine, and carvedilol, which have a higher affinity for AAG, desialylation significantly changes free drug concentrations. In contrast, drugs such as propranolol, imipramine, and vinblastine, which have a strong albumin binding, show only minimal changes. It is noteworthy that the free drug concentration of dipyridamole is particularly sensitive to changes in AAG concentration and glycosylation, with a decrease of up to 15% being observed, underscoring the need for dosage adjustments in personalized medicine.
PubMed: 38399284
DOI: 10.3390/pharmaceutics16020230 -
Journal of Cardiovascular Development... Jan 2024To improve the efficacy over antiplatelet monotherapy, dual antiplatelet therapy (DAPT) has been increasingly adopted in the management of non-cardioembolic stroke. For... (Review)
Review
To improve the efficacy over antiplatelet monotherapy, dual antiplatelet therapy (DAPT) has been increasingly adopted in the management of non-cardioembolic stroke. For minor ischemic stroke and high-risk transient ischemic attack, the aspirin-clopidogrel combination is now recommended for acute short-term treatment, whereas aspirin-ticagrelor combination may be considered in selected patients, especially those with resistance to clopidogrel. For long-term stroke prevention, aspirin-dipyridamole combination has been used as an alternative to antiplatelet monotherapy, and aspirin or clopidogrel combined with cilostazole may be prescribed for added protection in high-risk patients. In this paper, we review the development of DAPT from a historical perspective and describe the findings from major clinical trials published up until the end of 2023. Using the 2021 American Heart Association guideline for secondary stroke prevention as a basis for our recommendations, we further discuss areas of controversy and more recent developments to provide an updated review for clinicians to consider in their daily practice.
PubMed: 38392262
DOI: 10.3390/jcdd11020048 -
Journal of the American Heart... Feb 2024Resting coronary flow velocity (CFV) in the mid-distal left anterior descending coronary artery can be easily assessed with transthoracic echocardiography. In this... (Observational Study)
Observational Study
BACKGROUND
Resting coronary flow velocity (CFV) in the mid-distal left anterior descending coronary artery can be easily assessed with transthoracic echocardiography. In this observational study, the authors sought to assess the relationship between resting CFV, CFV reserve (CFVR), and outcome in patients with chronic coronary syndromes.
METHODS AND RESULTS
In a prospective multicenter study design, the authors retrospectively analyzed 7576 patients (age, 66±11 years; 4312 men) with chronic coronary syndromes and left ventricular ejection fraction ≥50% referred for dipyridamole stress echocardiography. Recruitment (years 2003-2021) involved 7 accredited laboratories, with interobserver variability <10% for CFV measurement at study entry. Baseline peak diastolic CFV was obtained by pulsed-wave Doppler in the mid-distal left anterior descending coronary artery. CFVR (abnormal value ≤2.0) was assessed with dipyridamole. All-cause death was the only end point. The mean CFV of the left anterior descending coronary artery was 31±12 cm/s. The mean CFVR was 2.32±0.60. During a median follow-up of 5.9±4.3 years, 1121 (15%) patients died. At multivariable analysis, resting CFV ≥32 cm/s was identified by a receiver operating curve as the best cutoff and was independently associated with mortality (hazard ratio [HR], 1.24 [95% CI, 1.10-1.40]; <0.0001) together with CFVR ≤2.0 (HR, 1.78 [95% CI, 1.57-2.02]; <0.0001), age, diabetes, history of coronary surgery, and left ventricular ejection fraction. When both CFV and CFVR were considered, the mortality rate was highest in patients with resting CFV ≥32 cm/s and CFVR ≤2.0 and lowest in patients with resting CFV <32 cm/s and CFVR >2.0.
CONCLUSIONS
High resting CFV is associated with worse survival in patients with chronic coronary syndromes and left ventricular ejection fraction ≥50%. The value is independent and additive to CFVR. The combination of high resting CFV and low CFVR is associated with the worst survival.
Topics: Male; Humans; Middle Aged; Aged; Prospective Studies; Retrospective Studies; Stroke Volume; Ventricular Function, Left; Coronary Vessels; Dipyridamole; Coronary Circulation; Echocardiography, Stress; Blood Flow Velocity
PubMed: 38362899
DOI: 10.1161/JAHA.123.031270 -
Pakistan Journal of Medical Sciences 2024To investigate the effect of flunarizine combined with ginkgo leaf extract and dipyridamole injection (GDI) on hemorheology of elderly patients with vertigo.
OBJECTIVE
To investigate the effect of flunarizine combined with ginkgo leaf extract and dipyridamole injection (GDI) on hemorheology of elderly patients with vertigo.
METHODS
Clinical data of 105 elderly patients with vertigo who were treated in The First People's Hospital of Lin'an District from June 2019 to December 2022 were retrospectively selected. Of them, 54 patients received flunarizine combined with GDI (Study group) while 51 patients received flunarizine treatment alone (Control group). The treatment effect and adverse reactions of the two groups, functional rehabilitation before and after treatment, including the Simplified Vertigo Symptom Score Scale (VSS-SF), Berg Balance Scale (BBS), and Dizziness Handicap Inventory (DHI) were measured. Hemodynamics including blood flow velocity (Vm) of basilar artery (BA), left vertebral artery (LVA), and right vertebral artery (RVA) before and after treatment were also assessed.
RESULTS
The total efficacy of the treatment in the study group was higher than that in the control group (94.4 % . 75.9%; P<0.05). After the treatment, the Vm of the BA, LVA, and RVA was increased in both groups compared to before treatment, and the increase was greater in the study group than in the control group (P<0.05). In addition, the BBS scores of the two groups after the treatment were higher than before the treatment, while the DHI and VSS-SF scores were lower than before the treatment. BBS scores of the study group were higher than those of the control group, while the DHI and VSS-SF scores were lower than those of the control group (P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the study group (5.6%) and the control group (2.0%; P>0.05).
CONCLUSIONS
The combination of flunarizine and GDI in elderly patients with vertigo can effectively regulate hemodynamics of the patient, reduce the degree of vertigo, improve balance, and have a significant overall therapeutic effect without increasing the risk of adverse reactions.
PubMed: 38356833
DOI: 10.12669/pjms.40.3.8456 -
Blood Advances Mar 2024Adult T-cell leukemia/lymphoma (ATL) is triggered by infection with human T-cell lymphotropic virus-1 (HTLV-1). Here, we describe the reprogramming of pyrimidine...
Adult T-cell leukemia/lymphoma (ATL) is triggered by infection with human T-cell lymphotropic virus-1 (HTLV-1). Here, we describe the reprogramming of pyrimidine biosynthesis in both normal T cells and ATL cells through regulation of uridine-cytidine kinase 2 (UCK2), which supports vigorous proliferation. UCK2 catalyzes the monophosphorylation of cytidine/uridine and their analogues during pyrimidine biosynthesis and drug metabolism. We found that UCK2 was overexpressed aberrantly in HTLV-1-infected T cells but not in normal T cells. T-cell activation via T-cell receptor (TCR) signaling induced expression of UCK2 in normal T cells. Somatic alterations and epigenetic modifications in ATL cells activate TCR signaling. Therefore, we believe that expression of UCK2 in HTLV-1-infected cells is induced by dysregulated TCR signaling. Recently, we established azacitidine-resistant (AZA-R) cells showing absent expression of UCK2. AZA-R cells proliferated normally in vitro, whereas UCK2 knockdown inhibited ATL cell growth. Although uridine and cytidine accumulated in AZA-R cells, possibly because of dysfunction of pyrimidine salvage biosynthesis induced by loss of UCK2 expression, the amount of UTP and CTP was almost the same as in parental cells. Furthermore, AZA-R cells were more susceptible to an inhibitor of dihydroorotic acid dehydrogenase, which performs the rate-limiting enzyme of de novo pyrimidine nucleotide biosynthesis, and more resistant to dipyridamole, an inhibitor of pyrimidine salvage biosynthesis, suggesting that AZA-R cells adapt to UCK2 loss by increasing de novo pyrimidine nucleotide biosynthesis. Taken together, the data suggest that fine-tuning pyrimidine biosynthesis supports vigorous cell proliferation of both normal T cells and ATL cells.
Topics: Adult; Humans; Pyrimidines; Uridine; Cell Proliferation; Cytidine; Human T-lymphotropic virus 1; Pyrimidine Nucleotides; Receptors, Antigen, T-Cell; T-Lymphocytes
PubMed: 38190613
DOI: 10.1182/bloodadvances.2023011131