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 * aplikace a dávkování terapeutické užití škodlivé účinky MeSH
- dvojitá slepá metoda MeSH
- extracelulární vezikuly * metabolismus účinky léků MeSH
- inhibitory agregace trombocytů * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- inhibitory faktoru Xa * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- kardiovaskulární nemoci * krev prevence a kontrola farmakoterapie MeSH
- kombinovaná farmakoterapie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mediátory zánětu krev MeSH
- prospektivní studie MeSH
- proteomika metody MeSH
- rivaroxaban * aplikace a dávkování MeSH
- senioři MeSH
- trombóza krev prevence a kontrola farmakoterapie MeSH
- výsledek terapie MeSH
- zánět krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie 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.
Prokinetika jsou skupinou léčiv, které díky schopnosti stimulace hladké svaloviny zvyšují motilitu trávicího traktu, a to především v jeho proximální části. V současnosti se prokinetika využívají primárně pro léčbu funkční dyspepsie, ale uplatnění mohou nalézt i u jiných indikací. Pozitivního účinku na motilitu dosahují prostřednictvím mechanismů, které jsou v rámci skupiny prokinetik do značné míry heterogenní. Článek poskytuje čtenářům základní přehled informací vztahujícím se k jednotlivým prokinetikům aktuálně registrovaných na trhu v České republice, blíže popisuje jejich farmakologické účinky a diskutuje užití prokinetik v léčbě funkční dyspepsie a refluxní nemoci jícnu, což jsou nejčastější indikace k užití prokinetik v klinické praxi.
Prokinetics are a group of drugs that, due to their ability to stimulate smooth muscle contraction, enhance the motility of the digestive tract, particularly in its proximal part. Currently, prokinetics are primarily used to treat functional dyspepsia, though they may also be prescribed for other indications. They exert their positive effects on motility through mechanisms that vary within this drug class. This article provides readers with a basic overview of the prokinetic agents currently registered on the market in the Czech Republic, describes their pharmacological effects in more detail, and discusses the use of prokinetics in the treatment of functional dyspepsia and gastroesophageal reflux disease, which are the most common indications for the use of prokinetics in clinical practice.
- Klíčová slova
- prokinetika, cinitaprid, itoprid,
- MeSH
- benzamidy aplikace a dávkování farmakologie MeSH
- dyspepsie farmakoterapie MeSH
- gastroezofageální reflux farmakoterapie MeSH
- gastrointestinální látky * aplikace a dávkování klasifikace MeSH
- gastrointestinální motilita * účinky léků MeSH
- gastrointestinální nemoci farmakoterapie MeSH
- lidé MeSH
- metoklopramid farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
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
- bradavice * farmakoterapie terapie MeSH
- dítě * MeSH
- fluoruracil farmakologie terapeutické užití MeSH
- infekce papilomavirem přenos terapie MeSH
- keratinocyty patologie MeSH
- kryoterapie metody MeSH
- kyselina salicylová terapeutické užití MeSH
- kyselina trichloroctová terapeutické užití MeSH
- lasery MeSH
- lidé MeSH
- podofylin farmakologie terapeutické užití MeSH
- Check Tag
- dítě * MeSH
- lidé MeSH
Gynekomastie je benigní zvětšení prsní žlázy u mužů, které může mít významný psychologický dopad, zejména u dětí a adolescentů. Tento článek se zabývá farmakologicky indukovanou gynekomastií a nejčastějšími léky, které mohou přispět k jejímu vzniku. V rámci naší analýzy jsme identifikovali a přezkoumali relevantní studie a kazuistiky publikované v databázi PubMed, které se zabývají různými aspekty gynekomastie u dětských pacientů. Důležitým krokem v prevenci gynekomastie je informovanost zdravotnického personálu, rodičů a pacientů o potenciálních rizicích spojených s užíváním určitých léků. Je nevyhnutelné, aby při předepisovaní léčby byly zohledněny veškeré možné vedlejší účinky, a aby se provedlo důkladné zhodnocení poměru přínosů a rizik. Mimo jiné se doporučuje provádět pravidelné kontroly a hodnocení pacientů, kteří užívají rizikové léky, aby bylo možné včas identifikovat a řešit případné příznaky gynekomastie. Tento článek zdůrazňuje potřebu zvýšené pozornosti k vybraným lékům, které jsou nejčastěji uváděny v odborné literatuře, a multidisciplinární přístup k léčbě. Informovanost o farmakologických rizicích a podpora ze strany zdravotnických odborníků jsou klíčové pro prevenci a zvládnutí tohoto stavu, ale také pro psychologickou pohodu dětských pacientů trpících touto diagnózou.
Gynecomastia is a benign enlargement of breast tissue in males that can have significant psychological impacts, especially in children and adolescents. This article focuses on pharmacologically induced gynecomastia and the most common medications that may contribute to its development. In our analysis, we identified and examined relevant studies and case reports published in the PubMed database that discuss various aspects of gynecomastia in pediatric patients. An important step in the prevention of gynecomastia is the awareness of healthcare professionals, parents, and patients regarding the potential risks associated with the use of certain medications. It is essential that all possible side effects are considered when prescribing treatment and that a thorough assessment of the benefits and risks is conducted. Additionally, it is recommended to carry out regular check-ups and evaluations of patients who are taking high-risk medications to identify and address any symptoms of gynecomastia in a timely manner. This article emphasizes the need for increased attention to selected medications commonly cited in the scientific literature and a multidisciplinary approach to treatment. Awareness of pharmacological risks and support from healthcare professionals are crucial for the prevention and management of this condition, as well as for the psychological well-being of pediatric patients suffering from this diagnosis.
- MeSH
- antikonvulziva farmakologie škodlivé účinky MeSH
- antipsychotika farmakologie škodlivé účinky MeSH
- dítě MeSH
- gynekomastie * etiologie MeSH
- isoniazid farmakologie škodlivé účinky MeSH
- lidé MeSH
- metoklopramid farmakologie škodlivé účinky MeSH
- nežádoucí účinky léčiv * farmakoterapie MeSH
- omeprazol farmakologie škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
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
- bradavice * terapie MeSH
- dítě * MeSH
- imunoterapie metody MeSH
- infekce papilomavirem farmakoterapie terapie MeSH
- keratinocyty účinky léků MeSH
- kryoterapie metody MeSH
- kyselina salicylová farmakologie terapeutické užití MeSH
- lasery MeSH
- lidé MeSH
- retinoidy farmakologie terapeutické užití MeSH
- Check Tag
- dítě * MeSH
- lidé 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 * terapeutické užití MeSH
- ateroskleróza MeSH
- cévní mozková příhoda prevence a kontrola MeSH
- dvojitá slepá metoda MeSH
- fibrinolytika terapeutické užití MeSH
- inhibitory agregace trombocytů terapeutické užití MeSH
- koronární angioplastika metody MeSH
- krvácení chemicky indukované MeSH
- lidé středního věku MeSH
- lidé MeSH
- podpůrné srdeční systémy * MeSH
- prospektivní studie MeSH
- senioři MeSH
- srdeční selhání MeSH
- trombóza prevence a kontrola MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- komentáře MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie 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
- antikoagulancia * škodlivé účinky aplikace a dávkování terapeutické užití MeSH
- Aspirin škodlivé účinky terapeutické užití aplikace a dávkování MeSH
- fraktury femuru chirurgie MeSH
- fraktury proximálního femuru MeSH
- inhibitory agregace trombocytů * škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- warfarin škodlivé účinky terapeutické užití aplikace a dávkování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy 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
- antioxidancia * farmakologie izolace a purifikace chemie MeSH
- fytonutrienty farmakologie izolace a purifikace MeSH
- hydroxybenzoáty * izolace a purifikace farmakologie chemie MeSH
- kořeny rostlin * chemie MeSH
- molekulární struktura MeSH
- Scorzonera * chemie MeSH
- seskviterpeny farmakologie izolace a purifikace chemie MeSH
- Publikační typ
- časopisecké články 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
- antikoagulancia * škodlivé účinky terapeutické užití MeSH
- Aspirin * škodlivé účinky terapeutické užití MeSH
- cévní mozková příhoda * etiologie prevence a kontrola MeSH
- dvojitá slepá metoda MeSH
- embolie * etiologie prevence a kontrola MeSH
- fibrilace síní * komplikace diagnóza MeSH
- inhibitory faktoru Xa škodlivé účinky terapeutické užití MeSH
- krvácení chemicky indukované MeSH
- lidé MeSH
- pyridony škodlivé účinky MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Geografické názvy
- Kanada MeSH
