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Ugeskrift For Laeger Apr 2024Pre-eclampsia affects 3-4% of pregnancies and is associated with maternal and infant mortality and morbidity. High-risk pregnancies in Denmark are recommended... (Review)
Review
Pre-eclampsia affects 3-4% of pregnancies and is associated with maternal and infant mortality and morbidity. High-risk pregnancies in Denmark are recommended prophylactic low-dose acetylsalicylic acid (LDA). If new screening algorithms are implemented, LDA will be recommended to around 10% of pregnant women. The use of LDA may slightly increase the risk of minor bleeding disturbances. Otherwise, there is a lot of promising data regarding the safety of LDA use during pregnancy, as argued in this review.
Topics: Humans; Pre-Eclampsia; Pregnancy; Aspirin; Female; Platelet Aggregation Inhibitors
PubMed: 38704715
DOI: 10.61409/V10230682 -
PloS One 2023Endothelial cells synthesize biochemical signals to coordinate a response to insults, resolve inflammation and restore barrier integrity. Vascular cells release a...
Endothelial cells synthesize biochemical signals to coordinate a response to insults, resolve inflammation and restore barrier integrity. Vascular cells release a variety of vasoactive bioactive lipid metabolites during the inflammatory response and produce pro-resolving mediators (e.g., Lipoxin A4, LXA4) in cooperation with leukocytes and platelets to bring a halt to inflammation. Aspirin, used in a variety of cardiovascular and pro-thrombotic disorders (e.g., atherosclerosis, angina, preeclampsia), potently inhibits proinflammatory eicosanoid formation. Moreover, aspirin stimulates the synthesis of pro-resolving lipid mediators (SPM), so-called Aspirin-Triggered Lipoxins (ATL). We demonstrate that cytokines stimulated a time- and dose-dependent increase in PGI2 (6-ketoPGF1α) and PGE2 formation that is blocked by aspirin. Eicosanoid production was caused by cytokine-induced expression of cyclooxygenase-2 (COX-2). We also detected increased production of pro-resolving LXA4 in cytokine-stimulated endothelial cells. The R-enantiomer of LXA4, 15-epi-LXA4, was enhanced by aspirin, but only in the presence of cytokine challenge, indicating dependence on COX-2 expression. In contrast to previous reports, we detected arachidonate 5-lipoxygenase (ALOX5) mRNA expression and its cognate protein (5-lipoxygenase, 5-LOX), suggesting that endothelial cells possess the enzymatic machinery necessary to synthesize both pro-inflammatory and pro-resolving lipid mediators independent of added leukocytes or platelets. Finally, we observed that, endothelial cells produced LTB4 in the absence of leukocytes. These results indicate that endothelial cells produce both pro-inflammatory and pro-resolving lipid mediators in the absence of other cell types and aspirin exerts pleiotropic actions influencing both COX and LOX pathways.
Topics: Humans; Aspirin; Cyclooxygenase 2; Endothelial Cells; Lipoxins; Inflammation; Eicosanoids; Cytokines
PubMed: 37098090
DOI: 10.1371/journal.pone.0283163 -
Wiley Interdisciplinary Reviews.... Sep 2020Epidemiological data indicate that long-term low dose aspirin administration has a protective effect against the occurrence of colorectal cancer, both in sporadic and in... (Review)
Review
Epidemiological data indicate that long-term low dose aspirin administration has a protective effect against the occurrence of colorectal cancer, both in sporadic and in hereditary forms of the disease. The mechanisms underlying this protective effect, however, are incompletely understood. The molecular events that lead to protection have been partly defined, but remain to be fully characterized. So far, however, approaches based on evolutionary dynamics have not been discussed much, but can potentially offer important insights. The aim of this review is to highlight this line of investigation and the results that have been obtained. A core observation in this respect is that aspirin has a direct negative impact on the growth dynamics of the cells, by influencing the kinetics of tumor cell division and death. We discuss the application of mathematical models to experimental data to quantify these parameter changes. We then describe further mathematical models that have been used to explore how these aspirin-mediated changes in kinetic parameters influence the probability of successful colony growth versus extinction, and how they affect the evolution of the tumor during aspirin administration. Finally, we discuss mathematical models that have been used to investigate the selective forces that can lead to the rise of mismatch-repair deficient cells in an inflammatory environment, and how this selection can be potentially altered through aspirin-mediated interventions. This article is categorized under: Models of Systems Properties and Processes > Mechanistic Models Analytical and Computational Methods > Analytical Methods Analytical and Computational Methods > Computational Methods.
Topics: Aspirin; Cell Cycle Checkpoints; Cell Proliferation; Evolution, Molecular; Humans; Models, Theoretical; Neoplasms
PubMed: 32163237
DOI: 10.1002/wsbm.1487 -
Hematology. American Society of... Dec 2020Venous thromboembolism (VTE; deep vein thrombosis and/or pulmonary embolism) is a well-established cause of morbidity and mortality in the medical and surgical patient... (Review)
Review
Venous thromboembolism (VTE; deep vein thrombosis and/or pulmonary embolism) is a well-established cause of morbidity and mortality in the medical and surgical patient populations. Clinical research in the prevention and treatment of VTE has been a dynamic field of study, with investigations into various treatment modalities ranging from mechanical prophylaxis to the direct oral anticoagulants. Aspirin has long been an inexpensive cornerstone of arterial vascular disease therapy, but its role in the primary or secondary prophylaxis of VTE has been debated. Risk-benefit tradeoffs between aspirin and anticoagulants have changed, in part due to advances in surgical technique and postoperative care, and in part due to the development of safe, easy-to-use oral anticoagulants. We review the proposed mechanisms in which aspirin may act on venous thrombosis, the evidence for aspirin use in the primary and secondary prophylaxis of VTE, and the risk of bleeding with aspirin as compared with anticoagulation.
Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Hemorrhage; Humans; Male; Venous Thromboembolism
PubMed: 33275727
DOI: 10.1182/hematology.2020000150 -
JACC. Cardiovascular Interventions Feb 2021
Topics: Aspirin; Humans; Pharmaceutical Preparations; Platelet Aggregation Inhibitors; Stents; Treatment Outcome
PubMed: 33602440
DOI: 10.1016/j.jcin.2020.12.040 -
Current Hypertension Reports Feb 2020To review the rationale and biological plausibility and discuss the current research on novel interventions for the prevention of preeclampsia. (Review)
Review
PURPOSE OF REVIEW
To review the rationale and biological plausibility and discuss the current research on novel interventions for the prevention of preeclampsia.
RECENT FINDINGS
Preeclampsia affects up to 8% of pregnancies worldwide and remains a major cause of maternal and neonatal morbidity and mortality. Multiple medications have been investigated or repurposed as potential effective interventions for preeclampsia prevention. Aspirin is currently the only drug for which there is some evidence of benefit for preeclampsia prevention, and its use is recommended by professional societies for pregnancies at risk. Statins have shown promise for prevention of preeclampsia in animal models and human pilot studies, without any trend or concerns for safety signals or teratogenicity. The use of metformin has also gained popularity in experimental studies, but observations from randomized clinical trials were not consistent on its utility as a possible intervention for preeclampsia prevention. While initial studies evaluating esomeprazole were promising, randomized trials failed to show benefit. Contemporary research shows exciting new opportunities for prophylactic treatment for preeclampsia, to prevent this debilitating and life-threatening disease.
Topics: Animals; Aspirin; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Pre-Eclampsia; Pregnancy
PubMed: 32052203
DOI: 10.1007/s11906-020-1026-8 -
PloS One 2015Antiplatelet therapy is widely used for the primary or secondary prevention of stroke. Drugs like clopidogrel have emerged as alternatives for traditional antiplatelet... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND AND PURPOSE
Antiplatelet therapy is widely used for the primary or secondary prevention of stroke. Drugs like clopidogrel have emerged as alternatives for traditional antiplatelet therapy, and dual therapy with clopidogrel and aspirin is of particular interest. We conducted this meta-analysis to systematically review studies about dual therapy comparing monotherapy with aspirin alone.
METHODS
Randomized controlled trials were searched in PubMed (1966-May, 2015), EMBASE (1947-May, 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (1948-May, 2015), WHO International Clinical Trial (ICTRP) (2004-May, 2015), China Biology Medicine disc (CBM disc) (1978-May, 2015) and were included into the final analysis according to the definite inclusion criteria mentioned in the study selection section. Risk ratio (RR) was pooled with 95% confidence interval (CI) for dichotomous data. The heterogeneity was considered significant if the χ2 test was significant (P value < 0.10) or the I2 > 50.00%. Subgroup analyses were carried out on the long and short time periods, the race and region.
RESULTS
We included 5 studies involving 24,084 patients. A pooled analysis showed that dual therapy with clopidogrel and aspirin had a lower stroke incidence than monotherapy in both the short term and long term (RR = 0.69, 95% CI: 0.59-0.82, P <0.05; RR = 0.84, 95% CI: 0.72-0.98, P = 0.03, respectively). With regard to safety, dual therapy had a higher risk of bleeding than monotherapy for both periods (RR = 1.51, 95% CI: 1.03-2.23, P = 0.04; RR = 1.54, 95% CI: 1.32-1.79, P<0.05, respectively).
CONCLUSIONS
Dual therapy with clopidogrel and aspirin could be a preferable choice to prevent stroke in patients who have had a previous stroke or transient ischemic attack, as well as those who are at high risk for stroke. And the effect of dual therapy seems to be more obvious for short-term. However, it is associated with a higher risk of bleeding.
Topics: Aspirin; Clopidogrel; Female; Hemorrhage; Humans; Male; Stroke; Ticlopidine
PubMed: 26270530
DOI: 10.1371/journal.pone.0135372 -
Clinical Pharmacokinetics Apr 2022Aspirin is one of the most widely used medicines. Although aspirin is commonly utilized for the treatment of several medical conditions, its broadest uptake is for the... (Review)
Review
Aspirin is one of the most widely used medicines. Although aspirin is commonly utilized for the treatment of several medical conditions, its broadest uptake is for the prevention of recurrent ischemic events in patients with atherosclerotic disease. Its mechanism of action of inhibiting platelet activation via blockade of thromboxane A production is unique and is not covered by any other antiplatelet agents. While plain, uncoated, immediate-release aspirin is used in acute settings to help assure rapid absorption, enteric-coated aspirin formulations dominate current chronic use, particularly in North America, including for secondary prevention of cardiovascular events. The unmet needs with current aspirin formulations include a high risk of gastrointestinal (GI) adverse events with plain aspirin, which enteric-coated formulations are not able to overcome, and subject to erratic absorption leading to reduced drug bioavailability. These observations underscore the need for aspirin formulations with a more favorable safety and efficacy profile. Phospholipid-aspirin complex (PL-ASA) is a novel formulation designed to address these needs. It is associated with reduced local acute GI injury compared with plain aspirin, and predictable absorption resulting in more reliable platelet inhibition compared with enteric-coated tablets. This review explores the rationale and pharmacologic profile of PL-ASA intended to address the unmet needs for aspirin therapy.
Topics: Aspirin; Blood Platelets; Humans; Phospholipids; Platelet Aggregation Inhibitors; Tablets, Enteric-Coated
PubMed: 35060092
DOI: 10.1007/s40262-021-01090-2 -
JACC. Cardiovascular Interventions May 2024
Topics: Humans; Aspirin; Drug Administration Schedule; Hemorrhage; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 38811106
DOI: 10.1016/j.jcin.2024.04.020 -
Thrombosis and Haemostasis Mar 2022
Topics: Aspirin; Cardiovascular Diseases; Humans; Platelet Aggregation Inhibitors; Primary Prevention; Secondary Prevention
PubMed: 35052007
DOI: 10.1055/s-0041-1740639