ABSTRACT
Background Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized. Objectives This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PRE dicting bleeding Complications in patients undergoing stent Implantation and Sub sequent Dual Anti Platelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting. Methods Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT. Results Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity. Conclusions Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT. (AU)
Subject(s)
Humans , Cardiovascular Diseases/prevention & control , Nutrition Assessment , Diet, Food, and NutritionABSTRACT
Iron oxide nanoparticles, with diameters around 12nm, were synthesized by coprecipitation method. The magnetic properties indicate a superparamagnetic behavior with a coercive field of 9.7Oe and a blocking temperature of 118K. Both aqueous and solid magnetoliposomes containing magnetite nanoparticles have sizes below 150nm, suitable for biomedical applications. Interaction between both types of magnetoliposomes and models of biological membranes was proven. A new antitumor compound, a diarylurea derivative of thienopyridine, active against breast cancer, was incorporated in both aqueous and solid magnetoliposomes, being mainly located in the lipid membrane. A promising application of these magnetoliposomes in oncology is anticipated, allowing a combined therapeutic approach, using both chemotherapy and magnetic hyperthermia.
Subject(s)
Ferric Compounds/chemistry , Liposomes/chemistry , Magnetite Nanoparticles/chemistry , Breast Neoplasms , Humans , Hyperthermia, Induced , Pyridines/chemistry , TemperatureABSTRACT
The damaging consequences of oxidative stress are known to be involved in several pathologies. So, the development of new drugs that can aid cells to cope with excessive levels of free radicals still assumes great relevance. Here, we investigated the antioxidant properties of four novel di(hetero)arylamines (named MJQ1, MJQ3, MJQ4 and MJQ5), sharing a common benzo[b]thiophene nucleus (an indole analogue), against oxidative damage induced to H9c2 myoblasts. Cell proliferation, evaluated by the sulforhodamine B assay, was not compromised by the presence of any of these compounds for concentrations below 50 µM (at 24 h) and 1 µM (72 h). Moreover, all of them showed a dose-dependent protective effect against tert-butylhydroperoxide (t-BHP)-induced cell death for concentrations in the nanomolar range. Their ability to scavenge free radicals seems to account for their protective effects, as they were able to prevent almost completely, at 25 nM, t-BHP-induced intracellular ROS formation, assessed by DCF fluorescence. Furthermore, their relatively high partition coefficient values are indicative of their ability to easily permeate lipid membranes and act intracellularly. Additionally, these novel diarylamines led to a reduction, between 60-70%, of the amount of DNA strand breaks induced by t-BHP, evaluated by the Comet assay, and lipid peroxidation (TBARS assay) induced by the oxidant pair ascorbate/iron. In all these parameters, which show their ability to prevent the oxidation of the main biomolecules, their protective role was superior to the traditional antioxidant Trolox. Although the mechanisms underlying the action of these diarylamines are currently under investigation, the data obtained so far reveals their high pharmacological potential as antioxidant molecules.
