BACKGROUND: Despite secondary prevention with aspirin, patients with stable cardiovascular disease (CVD) remain at elevated long-term risk of major adverse cardiovascular events. The Cardiovascular Outcomes in People Using Anticoagulant Strategies (COMPASS) double-blind, randomized clinical trial demonstrated that aspirin plus low-dose rivaroxaban (COMPASS regime) significantly decreased the incidence of major adverse cardiovascular events by 24% compared with aspirin alone. However, the mechanisms underlying these potential synergistic/nonantithrombotic effects remain elusive. Extracellular vesicles (EVs) are crucial messengers regulating a myriad of biological/pathological processes and are highly implicated in CVD. OBJECTIVES: We hypothesized that circulating EV profiles reflect the cardioprotective properties of the COMPASS regime. METHODS: A cohort of stable CVD patients (N = 40) who participated in the COMPASS trial and were previously randomized to receive aspirin were prospectively recruited and assigned a revised regimen of open-label aspirin plus rivaroxaban. Blood samples were obtained at baseline (aspirin only) and 6-month follow-up. Plasma EV concentration, size, and origin were analyzed by nanoparticle tracking analysis and flow cytometry. EVs were enriched by ultracentrifugation for proteomic analysis. RESULTS: The COMPASS regime fundamentally altered small (<200 nm) and large (200-1000 nm) EV concentration and size compared with aspirin alone. Crucially, levels of platelet-derived and myeloperoxidase-positive EVs became significantly decreased at follow-up. Comparative proteomic characterization further revealed a significant decrease in highly proinflammatory protein expression at follow-up. CONCLUSION: The observed changes in EV subpopulations, together with the differential protein expression profiles, suggest amelioration of an underlying proinflammatory and prothrombotic state upon dual therapy, which may be of clinical relevance toward understanding the fundamental mechanism underlying the reported superior cardiovascular outcomes associated with this antithrombotic regimen.
- MeSH
- Aspirin * administration & dosage therapeutic use adverse effects MeSH
- Double-Blind Method MeSH
- Extracellular Vesicles * metabolism drug effects MeSH
- Platelet Aggregation Inhibitors * administration & dosage adverse effects therapeutic use MeSH
- Factor Xa Inhibitors * administration & dosage adverse effects therapeutic use MeSH
- Cardiovascular Diseases * blood prevention & control drug therapy MeSH
- Drug Therapy, Combination * MeSH
- Middle Aged MeSH
- Humans MeSH
- Inflammation Mediators blood MeSH
- Prospective Studies MeSH
- Proteomics methods MeSH
- Rivaroxaban * administration & dosage MeSH
- Aged MeSH
- Thrombosis blood prevention & control drug therapy MeSH
- Treatment Outcome MeSH
- Inflammation blood MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Burkholderia cenocepacia are considered emerging pathogens classified as a public health problem due to extensive antimicrobial resistance. Therefore, the discovery of new therapeutic strategies has become crucial. This study aimed to evaluate the antimicrobial activity of gallic acid and methyl gallate against non-fermenting bacteria. The study included five clinical isolates of Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Burkholderia cenocepacia. The minimum inhibitory concentrations of gallic acid and methyl gallate were determined by the broth microdilution method. Growth curves, metabolic activity, and biofilm formation of each bacterial strain in the presence or absence of phenolic compounds were performed. Finally, the therapeutic efficacy of the compounds was evaluated using an in vivo model. Gallic acid and methyl gallate showed antibacterial activity against bacterial strains in a concentration range of 64 to 256 μg/mL, both compounds reduced bacterial growth and metabolic activity of the strains, even at subinhibitory concentrations. Only, methyl gallate exhibited activity to inhibit the formation of bacterial biofilms. Moreover, gallic acid and methyl gallate increased larval survival by up to 60% compared to 30% survival of untreated larvae in a bacterial infection model in Galleria mellonella. Our results highlight the potential of gallic acid and methyl gallate as therapeutic alternatives for infections by emerging non-fermentative bacteria.
Virové bradavice jsou celosvětově časté onemocnění způsobené lidským papilomavirem, který má řadu genotypů. Mnoho z těchto virů je komenzálních a u imunokompetentních hostitelů nevyvolávají žádné projevy. Za vhodných podmínek některé způsobují klinické změny na kůži nebo na sliznicích v anogenitální či orofaryngeální oblasti. U dětí se nejčastěji setkáváme s verruca vulgaris, verruca plantaris a verruca plana. Řada těchto projevů samovolně vymizí, problémem jsou perzistentní či úporně recidivující bradavice. Léčbou se snažíme nejen zlikvidovat viditelné změny za minimalizace bolesti a bez jizvení, ale také o prevenci recidivy ať již v místě původní bradavice nebo kdekoli jinde na těle.
Viral warts are a common disease worldwide caused by the human papillomavirus, which has a number of genotypes. Many of these viruses are commensal and do not cause any symptoms in immunocompetent hosts. Under appropriate conditions, however, some cause clinical changes on the skin or mucous membranes in the anogenital or oropharyngeal part. Verruca vulgaris, verruca plantaris and verruca plana are most often encountered in children. Many of these manifestations disappear on their own, the problem is persistent or stubbornly recurring warts. With the treatment, we try not only to eliminate visible changes while minimizing pain and without scarring, but also to prevent recurrence, whether at the site of the original wart or anywhere else on the body.
- MeSH
- Warts * drug therapy therapy MeSH
- Child * MeSH
- Fluorouracil pharmacology therapeutic use MeSH
- Papillomavirus Infections transmission therapy MeSH
- Keratinocytes pathology MeSH
- Cryotherapy methods MeSH
- Salicylic Acid therapeutic use MeSH
- Trichloroacetic Acid therapeutic use MeSH
- Lasers MeSH
- Humans MeSH
- Podophyllin pharmacology therapeutic use MeSH
- Check Tag
- Child * MeSH
- Humans MeSH
IMPORTANCE: The Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure (ARIES-HM3) study demonstrated that aspirin may be safely eliminated from the antithrombotic regimen after HeartMate 3 (HM3 [Abbott Cardiovascular]) left ventricular assist device (LVAD) implantation. This prespecified analysis explored whether conditions requiring aspirin (prior percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], stroke, or peripheral vascular disease [PVD]) would influence outcomes differentially with aspirin avoidance. OBJECTIVE: To analyze aspirin avoidance on hemocompatibility-related adverse events (HRAEs) at 1 year after implant in patients with a history of CABG, PCI, stroke, or PVD. DESIGN, SETTING, AND PARTICIPANTS: This was an international, multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial including patients implanted with a de novo HM3 LVAD across 51 centers. Data analysis was conducted from April to July 2024. INTERVENTIONS: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg per day) or placebo, in addition to a vitamin K antagonist (VKA) targeted to an international normalized ratio of 2 to 3 in both groups. MAIN OUTCOMES AND MEASURES: Primary end point (assessed for noninferiority) was a composite of survival free of any nonsurgical (>14 days after implant) HRAEs including stroke, pump thrombosis, bleeding, and arterial peripheral thromboembolism at 12 months. Secondary end points included nonsurgical bleeding, stroke, and pump thrombosis events. RESULTS: Among 589 of 628 patients (mean [SD] age, 57.1 [13.7] years; 456 male [77.4%]) who contributed to the primary end point analysis, a history of PCI, CABG, stroke, or PVD was present in 41% (240 of 589 patients). There was no interaction between the presence of an atherosclerotic vascular condition and effect of aspirin compared with placebo (P for interaction= .23). The preset 10% noninferiority margin was not crossed for the studied subgroup of patients. Thrombotic events were rare, with no differences between aspirin and placebo in patients with and without vascular disease (P for interaction = .77). Aspirin treatment was associated with a higher rate of nonsurgical major bleeding events in the group with prior vascular condition history compared with those without aspirin (rate ratio for placebo compared with aspirin, 0.52; 95% CI, 0.35-0.79). CONCLUSIONS AND RELEVANCE: Results of this prespecified analysis of the ARIES-HM3 randomized clinical trial demonstrate that in patients with advanced heart failure who have classical indications for antiplatelet therapy use at the time of LVAD implantation, aspirin avoidance was safe and not associated with increased thrombosis risk. Importantly, elimination of aspirin was associated with no increased thrombosis but a reduction in nonsurgical bleeding events in patients with a history of PCI, CABG, stroke, or PVD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069156.
- MeSH
- Aspirin * therapeutic use MeSH
- Atherosclerosis MeSH
- Stroke prevention & control MeSH
- Double-Blind Method MeSH
- Fibrinolytic Agents therapeutic use MeSH
- Platelet Aggregation Inhibitors therapeutic use MeSH
- Percutaneous Coronary Intervention methods MeSH
- Hemorrhage chemically induced MeSH
- Middle Aged MeSH
- Humans MeSH
- Heart-Assist Devices * MeSH
- Prospective Studies MeSH
- Aged MeSH
- Heart Failure MeSH
- Thrombosis prevention & control MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comment MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
Proximal femur fractures (PFF) pose a major challenge in elderly patients with severe comorbidities and receiving antithrombotic therapy since according to the latest guidelines the surgery should be performed as soon as possible, preferably within 24 hours, to reduce mortality and morbidity. This review outlines the practical approach to surgical management of PFF that relies on increasing evidence of safety of early surgery in patients with PFF receiving antiplatelet and anticoagulant therapy. We have also used information from the existing evidence-based guidelines for elective/planned surgery in patients with antithrombotic therapy. The practical approach can be summarised as follows: • Antiplatelet therapy - discontinuation of acetylsalicylic acid (ASA) and clopidogrel in monotherapy or in combination is not necessary prior to surgery. In case of bleeding, antifibrinolytic therapy is recommended as well as administration of platelet concentrate which is rarely needed. • In patients taking warfarin, reversal of its effects is recommended by early administration of vitamin K to allow surgery to be performed within 24 hours. Prothrombin complex concentrate (PCC) as a second-line drug is reserved for extreme cases only. Warfarin therapy is resumed 24 hours after surgery. • Direct oral anticoagulants must be discontinued 24-48 hours prior to surgery, possibly longer depending on the type of drug, time of administration of the last dose, and renal function. In extreme cases, an antidote (idarucizumab, off-label andexanet) can be administered prior to surgery, or PCC in case they are unavailable. Anticoagulation therapy is resumed in 24-48 hours. • Neuraxial anaesthesia is possible when ASA is taken by the patient and in case of effective warfarin reversal. • In early surgery and rapid restart of anticoagulant therapy, bridging therapy with LMWH is not indicated except for in cases with extreme risk of thrombosis. Key words: proximal femur fracture, antiplatelet therapy, anticoagulant therapy, perioperative management.
- MeSH
- Anticoagulants * adverse effects administration & dosage therapeutic use MeSH
- Aspirin adverse effects therapeutic use administration & dosage MeSH
- Femoral Fractures surgery MeSH
- Proximal Femoral Fractures MeSH
- Platelet Aggregation Inhibitors * adverse effects therapeutic use MeSH
- Humans MeSH
- Warfarin adverse effects therapeutic use administration & dosage MeSH
- Check Tag
- Humans MeSH
- Publication type
- English Abstract MeSH
- Journal Article MeSH
- Review MeSH
The antioxidant activity of Scorzonera parviflora Jacq. roots were assessed by measuring their ability to scavenge ABTS and DPPH radicals. Bioactivity-guided fractionation was utilized to identify the compound(s) responsible for this activity. The most active phase, ethyl acetate, was isolated using column chromatography. The resulting fractions were then purified using preparative TLC on reverse phase and semi-preparative HPLC. The structures of the pure compounds were elucidated by spectral analysis (MS and 1H, 13C, 2D-NMR). Three undescribed phenolic acid derivatives, namely parvifloric acid A (1), B (2), and C (3), and one new sesquiterpene lactone, parviflorin (4) together with seven known compounds were isolated and identified as scopolin (5), scopoletin (6), caffeic acid (7), protocatechuic acid (8), 4,5-O-dicaffeoylquinic acid (9) 3,5-O-dicaffeoylquinic acid (10), and 3,5-O-dicaffeoylquinic acid methyl ester (11). Finally, the pure compounds obtained were tested to evaluate their antioxidant capacities, using ABTS and DPPH radical scavenging potencies. The highest activity was observed with 3,5-O-dicaffeoylquinic acid (10), followed by its methyl ester.
- MeSH
- Antioxidants * pharmacology isolation & purification chemistry MeSH
- Phytochemicals pharmacology isolation & purification MeSH
- Hydroxybenzoates * isolation & purification pharmacology chemistry MeSH
- Plant Roots * chemistry MeSH
- Molecular Structure MeSH
- Scorzonera * chemistry MeSH
- Sesquiterpenes pharmacology isolation & purification chemistry MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit. METHODS: We conducted a trial involving patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all the patients who had undergone randomization); the primary safety outcome, major bleeding, was assessed in the on-treatment population (all the patients who had undergone randomization and received at least one dose of the assigned trial drug, with follow-up censored 5 days after permanent discontinuation of trial medication for any reason). RESULTS: We included 4012 patients with a mean (±SD) age of 76.8±7.6 years and a mean CHA2DS2-VASc score of 3.9±1.1 (scores range from 0 to 9, with higher scores indicating a higher risk of stroke); 36.1% of the patients were women. After a mean follow-up of 3.5±1.8 years, stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per patient-year) and in 86 patients in the aspirin group (1.24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007). In the on-treatment population, the rate of major bleeding was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P = 0.001). Fatal bleeding occurred in 5 patients in the apixaban group and 8 patients in the aspirin group. CONCLUSIONS: Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; ARTESIA ClinicalTrials.gov number, NCT01938248.).
- MeSH
- Anticoagulants * adverse effects therapeutic use MeSH
- Aspirin * adverse effects therapeutic use MeSH
- Stroke * etiology prevention & control MeSH
- Double-Blind Method MeSH
- Embolism * etiology prevention & control MeSH
- Atrial Fibrillation * complications diagnosis MeSH
- Factor Xa Inhibitors adverse effects therapeutic use MeSH
- Hemorrhage chemically induced MeSH
- Humans MeSH
- Pyridones adverse effects MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
- Geographicals
- Canada MeSH
Povídka o aspirinu je napínavá a komplikovaná. Pokusili jsme se rozklíčovat úlohu hlavních hrdinů, ale i široké pole biologických účinků kyseliny acetylsalicylové, superléku, jehož použití by dnes odpovědné instituce neschválily, a který i přesto patří k nejužívanějším lékům na Zemi i mimo ni (používali jej kosmonauté projektu Apollo na bolesti zubů). Snažili jsme se co nejvíce používat původní zdroje literatury s cílem narovnat některé dezinformace vyskytující se kolem tohoto tématu. Autoři jsou si vědomi, že Aspirin je chráněný název, který však v běžné lidské mluvě „zlidověl“.
The story of aspirin is exciting and complicated. We tried to decipher the role of the main characters, as well as a wide field of pharmacological roles of acetylsalicylic acid, a super-drug, which would not be approved by responsible institutions today but which is still one of the most used medicines on the Earth, as well as in the space (it was used by the astronauts in the Apollo project). Original literature sources were used as much as possible to clean up some misinformation around the topic. The authors are aware that Aspirin is a trademarked name but it has become "popular" in common human speech.
- MeSH
- Aspirin history therapeutic use MeSH
- Phytotherapy history MeSH
- Plant Bark MeSH
- Pharmaceutical Preparations * history MeSH
- Humans MeSH
- Drug Discovery history MeSH
- Salix MeSH
- Check Tag
- Humans MeSH
- Publication type
- Historical Article MeSH
The story of aspirin is exciting and complicated. We tried to decipher the role of the main characters, as well as a wide field of pharmacological roles of acetylsalicylic acid, a super-drug, which would not be approved by responsible institutions today but which is still one of the most used medicines on the Earth, as well as in the space (it was used by the astronauts in the Apollo project). Original literature sources were used as much as possible to clean up some misinformation around the topic. The authors are aware that Aspirin is a trademarked name but it has become "popular" in common human speech.
- MeSH
- Analgesics chemistry MeSH
- Antipyretics chemistry MeSH
- Aspirin * pharmacology therapeutic use MeSH
- Phytotherapy * methods MeSH
- Platelet Aggregation Inhibitors chemistry MeSH
- Pharmaceutical Preparations * chemistry history MeSH
- Humans MeSH
- Salicylates chemistry pharmacology therapeutic use MeSH
- Salix chemistry physiology MeSH
- Check Tag
- Humans MeSH
The effective treatment of inflammatory diseases, particularly their chronic forms, is a key task of modern medicine. Herein, we report the synthesis and evaluation of biocompatible polymer conjugates based on N-2-(hydroxypropyl)methacrylamide copolymers enabling the controlled release of acetylsalicylic acid (ASA)-based anti-inflammatory drugs under specific stimuli. All polymer nanotherapeutics were proposed as water-soluble drug delivery systems with a hydrodynamic size below 10 nm ensuring suitability for the parenteral application and preventing opsonization by the reticuloendothelial system. The nanotherapeutics bearing an ester-bound ASA exhibited long-term release of the ASA/salicylic acid mixture, while the nanotherapeutics carrying salicylic acid hydrazide (SAH) ensured the selective release of SAH in the acidic inflammatory environment thanks to the pH-sensitive hydrazone bond between the polymer carrier and SAH. The ASA- and SAH-containing nanotherapeutics inhibited both cyclooxygenase isoforms and/or the production of pro-inflammatory mediators. Thanks to their favorable design, they can preferentially accumulate in the inflamed tissue, resulting in reduced side effects and lower dosage, and thus more effective and safer treatment.
- MeSH
- Acrylamides chemistry pharmacology administration & dosage MeSH
- Anti-Inflammatory Agents pharmacology administration & dosage chemistry MeSH
- Aspirin * administration & dosage pharmacology chemistry MeSH
- Prostaglandin-Endoperoxide Synthases metabolism MeSH
- Cyclooxygenase Inhibitors pharmacology administration & dosage chemistry MeSH
- Delayed-Action Preparations * MeSH
- Inflammation Mediators metabolism MeSH
- Mice MeSH
- Nanoparticles * chemistry MeSH
- Drug Carriers chemistry MeSH
- Polymers * chemistry administration & dosage MeSH
- Drug Liberation MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
