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Aspirin has been known for a long time and currently stays as a cornerstone of antithrombotic therapy in cardiovascular disease. In patients with either acute or chronic coronary syndromes undergoing percutaneous coronary intervention aspirin is mandatory in a dual antiplatelet therapy regimen for prevention of stent thrombosis and/or new ischaemic events. Aspirin is also currently a first-option antithrombotic therapy after an aortic prosthetic valve replacement and is occasionally required in addition to oral anticoagulants after implantation of a mechanical valve. Presumed or demonstrated aspirin hypersensitivity is a main clinical problem, limiting the use of a life-saving medication. In the general population, aspirin hypersensitivity has a prevalence of 0.6%-2.5% and has a plethora of clinical presentations, ranging from aspirin-exacerbated respiratory disease to anaphylaxis. Although infrequent, when encountered in clinical practice aspirin hypersensitivity poses for cardiologists a clinical dilemma, which should never be trivialized, avoiding-as much as possible-omission of the drug. We here review the epidemiology of aspirin hypersensitivity, provide an outline of pathophysiological mechanisms and clinical presentations, and review management options, starting from a characterization of true aspirin allergy-in contrast to intolerance-to suggestion of desensitization protocols.
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Aspirina , Hipersensibilidad a las Drogas , Humanos , Aspirina/efectos adversos , Hipersensibilidad a las Drogas/epidemiología , Inhibidores de Agregación Plaquetaria/efectos adversos , Desensibilización Inmunológica/métodos , Intervención Coronaria Percutánea/efectos adversos , CardiólogosRESUMEN
Metabolomics is an emerging and powerful bioanalytical method supporting clinical investigations. Serum and plasma are commonly used without rational prioritization. Serum is collected after blood coagulation, a complex biochemical process involving active platelet metabolism. This may affect the metabolome and increase the variance, as platelet counts and function may vary substantially in individuals. A multiomics approach systematically investigating the suitability of serum and plasma for clinical studies demonstrated that metabolites correlated well (n = 461, R2 = 0.991), whereas lipid mediators (n = 83, R2 = 0.906) and proteins (n = 322, R2 = 0.860) differed substantially between specimen. Independently, analysis of platelet releasates identified most biomolecules significantly enriched in serum compared to plasma. A prospective, randomized, controlled parallel group metabolomics trial with acetylsalicylic acid administered for 7 days demonstrated that the apparent drug effects significantly differ depending on the analyzed specimen. Only serum analyses of healthy individuals suggested a significant downregulation of TXB2 and 12-HETE, which were specifically formed during coagulation in vitro. Plasma analyses reliably identified acetylsalicylic acid effects on metabolites and lipids occurring in vivo such as an increase in serotonin, 15-deoxy-PGJ2 and sphingosine-1-phosphate and a decrease in polyunsaturated fatty acids. The present data suggest that plasma should be preferred above serum for clinical metabolomics studies as the serum metabolome may be substantially confounded by platelets.
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Aspirina , Plaquetas , Metabolómica , Plasma , Humanos , Plaquetas/metabolismo , Plaquetas/efectos de los fármacos , Metabolómica/métodos , Aspirina/farmacología , Plasma/metabolismo , Plasma/química , Suero/metabolismo , Suero/química , Lisofosfolípidos/sangre , Esfingosina/análogos & derivados , Esfingosina/sangre , Metaboloma/efectos de los fármacos , Tromboxano B2/sangre , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/sangre , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Masculino , Femenino , Estudios Prospectivos , AdultoRESUMEN
This review focuses on the management of reproductive issues in women who have antiphospholipid syndrome (APS) or are carriers of antiphospholipid antibodies (aPL). The importance of aPL detection during preconception counselling relies on their pathogenic potential for placental insufficiency and related obstetric complications. The risk of adverse pregnancy outcomes can be minimized by individualized risk stratification and tailored treatment aimed at preventing placental insufficiency. Combination therapy of low-dose acetylsalicylic acid and heparin is the mainstay of prophylaxis during pregnancy; immunomodulation, especially with hydroxychloroquine, should be considered in refractory cases. Supplementary ultrasound surveillance is useful to detect fetal growth restriction and correctly tailor the time of delivery. The individual aPL profile must be considered in the stratification of thrombotic risk, such as during assisted reproduction techniques requiring hormonal ovarian stimulation or during the follow-up after pregnancy in order to prevent the first vascular event.
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Síndrome Antifosfolípido , Insuficiencia Placentaria , Complicaciones del Embarazo , Femenino , Embarazo , Humanos , Síndrome Antifosfolípido/complicaciones , Reumatólogos , Complicaciones del Embarazo/tratamiento farmacológico , Placenta , Resultado del EmbarazoRESUMEN
BACKGROUND: Sleep deficiencies, such as manifested in short sleep duration or insomnia symptoms, are known to increase the risk for multiple disease conditions involving immunopathology. Inflammation is hypothesized to be a mechanism through which deficient sleep acts as a risk factor for these conditions. Thus, one potential way to mitigate negative health consequences associated with deficient sleep is to target inflammation. Few interventional sleep studies investigated whether improving sleep affects inflammatory processes, but results suggest that complementary approaches may be necessary to target inflammation associated with sleep deficiencies. We investigated whether targeting inflammation through low-dose acetylsalicylic acid (ASA, i.e., aspirin) is able to blunt the inflammatory response to experimental sleep restriction. METHODS: 46 healthy participants (19F/27M, age range 19-63 years) were studied in a double-blind randomized placebo-controlled crossover trial with three protocols each consisting of a 14-day at-home monitoring phase followed by an 11-day (10-night) in-laboratory stay (sleep restriction/ASA, sleep restriction/placebo, control sleep/placebo). In the sleep restriction/ASA condition, participants took low-dose ASA (81 mg/day) daily in the evening (22:00) during the at-home phase and the subsequent in-laboratory stay. In the sleep restriction/placebo and control sleep/placebo conditions, participants took placebo daily. Each in-laboratory stay started with 2 nights with a sleep opportunity of 8 h/night (23:00-07:00) for adaptation and baseline measurements. Under the two sleep restriction conditions, participants were exposed to 5 nights of sleep restricted to a sleep opportunity of 4 h/night (03:00-07:00) followed by 3 nights of recovery sleep with a sleep opportunity of 8 h/night. Under the control sleep condition, participants had a sleep opportunity of 8 h/night throughout the in-laboratory stay. During each in-laboratory stay, participants had 3 days of intensive monitoring (at baseline, 5th day of sleep restriction/control sleep, and 2nd day of recovery sleep). Variables, including pro-inflammatory immune cell function, C-reactive protein (CRP), and actigraphy-estimated measures of sleep, were analyzed using generalized linear mixed models. RESULTS: Low-dose ASA administration reduced the interleukin (IL)-6 expression in LPS-stimulated monocytes (p<0.05 for condition*day) and reduced serum CRP levels (p<0.01 for condition) after 5 nights of sleep restriction compared to placebo administration in the sleep restriction condition. Low-dose ASA also reduced the amount of cyclooxygenase (COX)-1/COX-2 double positive cells among LPS-stimulated monocytes after 2 nights of recovery sleep following 5 nights of sleep restriction compared to placebo (p<0.05 for condition). Low-dose ASA further decreased wake after sleep onset (WASO) and increased sleep efficiency (SE) during the first 2 nights of recovery sleep (p<0.001 for condition and condition*day). Baseline comparisons revealed no differences between conditions for all of the investigated variables (p>0.05 for condition). CONCLUSION: This study shows that inflammatory responses to sleep restriction can be reduced by preemptive administration of low-dose ASA. This finding may open new therapeutic approaches to prevent or control inflammation and its consequences in those experiencing sleep deficiencies. TRIAL REGISTRATION: ClinicalTrials.gov NCT03377543.
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AIMS: The aim of this study was to systematically review whether concurrent treatment with an SSRI and low-dose ASA increases the risk of bleeding compared with treatment with an SSRI alone or ASA alone. METHODS: Medline, Embase, the Cochrane Library, PsycINFO and Web of Science (from database inception to January 2023) were searched according to PICO: P = patients on treatment with an SSRI and/or low-dose ASA; I = intervention: SSRI + ASA; C = comparison: ASA or SSRI alone; O = outcomes: bleeding/major bleeding. The included articles were assessed using checklists. Studies without major risk of bias formed the basis for the conclusions. Extracted data were pooled using random-effects meta-analyses. Certainty of evidence was assessed according to GRADE. RESULTS: Twenty-four studies met the PICO and were included. One randomized and six nonrandomized studies were assessed not to have major risk of bias. Regarding SSRI + ASA vs. ASA only, the pooled hazard ratio of three nonrandomized studies (n = 38 467) was 1.37 (95% confidence interval: 1.10; 1.70; I2 = 0%), and the pooled odds ratio of two nonrandomized studies (n = 28 296) was 0.95 (0.77; 1.19; I2 = 0%). Regarding SSRI + ASA vs. SSRI only, the randomized controlled trial (n = 1048) reported a hazard ratio of 1.82 (0.66; 5.02), the hazard ratio being 1.60 (1.24; 2.06) for ASA vs. placebo in patients without SSRI treatment; and one nonrandomized controlled study (n = 18 920) reported an incidence rate ratio of 1.03 (0.96; 1.12). CONCLUSIONS: The compiled evidence was too uncertain to support an interaction when an SSRI is added to low-dose ASA. Low-dose ASA added to an SSRI may imply an increased risk of bleeding primarily attributable to the initiation of ASA.
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Aspirina , Inhibidores Selectivos de la Recaptación de Serotonina , Humanos , Aspirina/efectos adversos , Quimioterapia Combinada , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversosRESUMEN
BACKGROUND: There is conflicting evidence on the role of acetylsalicylic acid (ASA) use in the development of cardiac allograft vasculopathy (CAV). METHODS: A nationwide prospective two-center study investigated changes in the coronary artery vasculature by highly automated 3-D optical coherence tomography (OCT) analysis at 1 month and 12 months after heart transplant (HTx). The influence of ASA use on coronary artery microvascular changes was analyzed in the overall study cohort and after propensity score matching for selected clinical CAV risk factors. RESULTS: In total, 175 patients (mean age 52 ± 12 years, 79% male) were recruited. During the 1-year follow-up, both intimal and media thickness progressed, with ASA having no effect on its progression. However, detailed OCT analysis revealed that ASA use was associated with a lower increase in lipid plaque (LP) burden (p = .013), while it did not affect the other observed pathologies. Propensity score matching of 120 patients (60 patient pairs) showed similar results, with ASA use associated with lower progression of LPs (p = .002), while having no impact on layered fibrotic plaque (p = .224), calcification (p = .231), macrophage infiltration (p = .197), or the absolute coronary artery risk score (p = .277). According to Kaplan-Meier analysis, ASA use was not associated with a significant difference in survival (p = .699) CONCLUSION: This study showed a benefit of early ASA use after HTx on LP progression. However, ASA use did not have any impact on the progression of other OCT-observed pathologies or long-term survival.
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Enfermedad de la Arteria Coronaria , Trasplante de Corazón , Placa Aterosclerótica , Humanos , Masculino , Adulto , Persona de Mediana Edad , Femenino , Enfermedad de la Arteria Coronaria/etiología , Estudios Prospectivos , Tomografía de Coherencia Óptica/efectos adversos , Tomografía de Coherencia Óptica/métodos , Aloinjertos/patología , Placa Aterosclerótica/complicaciones , Trasplante de Corazón/efectos adversos , Angiografía CoronariaRESUMEN
BACKGROUND: 1.5 million new HIV infections occurred in 2021, suggesting new prevention methods are needed. Inflammation increases the risk for HIV acquisition by attracting HIV target cells to the female genital tract (FGT). In a pilot study, acetylsalicylic acid (ASA/Aspirin) decreased the proportion of FGT HIV target cells by 35â¯%. However, the mechanism remains unknown. METHODS: Women from Nairobi, Kenya took low-dose ASA (81â¯mg) daily for 6-weeks. Free oxylipins in the plasma were quantified by high-performance liquid chromatography-tandem mass spectroscopy. RESULTS: Oxylipins from 9 fatty acid substrates were detected, with more than one analyte from 4 substrates reduced post-ASA. Summary analysis found ASA downregulated cyclooxygenase and lipoxygenase but not cytochrome P450 activity with a lower n-6/n-3 oxylipin profile, reflecting reduced inflammation post-ASA. CONCLUSIONS: Inflammation is associated with increased lipoxygenase activity and HIV risk. Our data suggests ASA reduces inflammation through downregulation of oxylipins. Understanding how ASA reduces inflammation may lead to novel HIV prevention approaches.
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Despite decades of investigations, the optimal assessment of the "therapeutic response" to early after loading dose of acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between pharmacodynamic (PD) and pharmacokinetic (PK) measurements assessed immediately after ASA administration. Serial PD and PK analyses were performed immediately after a single 162 or 650 mg dose of chewed and swallowed ASA in ten healthy adults. ASA response was defined as > 95% inhibition of serum thromboxane (Tx)B2, < 550 aspirin reaction units (ARU) by VerifyNow Aspirin (VN) test, and ≤ 20% arachidonic acid (AA)-induced platelet aggregation (PA). Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. ASA response measured by VN test and AA-induced PA was achieved within 30 min of ASA administration. A correlation was observed between ARU and AA-induced maximum PA (r = 0.69, p < 0.001), serum TxB2 (r = 0.74 and p < 0.001), and serum TxB2 inhibition (r = 0.79, p < 0.001). In ROC curve analyses, ≤ 558 ARU and ≤ 7% AA-induced PA were associated with > 95% inhibition of TxB2. 686 ng/ml plasma ASA cut-off point was associated with > 95% inhibition of serum TxB2, ≤ 7% 1 mM AA-induced PA, and ≤ 585 ARU. A modest ~ 50% inhibition of TxB2 inhibition was associated with marked inhibition of 1 mM AA-induced platelet aggregation by LTA. Our analyses demonstrated important relationships between pharmacodynamic, and pharmacokinetic parameters measured immediately following oral ASA and cutoff values for ARU and AA-induced PA that is associated with > 95% inhibition of serum TxB2.
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Aspirina , Inhibidores de Agregación Plaquetaria , Adulto , Humanos , Aspirina/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Tromboxano B2 , Agregación Plaquetaria , Tromboxanos , Ácido Araquidónico/farmacología , PlaquetasRESUMEN
VerifyNow (VN) test is a less laborious method to assess pharmacodynamics (PD) compared to light transmittance aggregometry (LTA). VN assay has not been used to study the immediate PD effects of acetylsalicylic acid (ASA). Ten healthy volunteers were randomly assigned to a single 162 or 650 mg dose of chewed and swallowed ASA. Pharmacodynamic and pharmacokinetic measurements were performed at baseline and serially up to 60 min after ASA administration. Onset by VN was 20 ± 7 min with 162 mg and 13 ± 7 min with 650 mg ASA (p = .07). Onset by 1 mM AA-induced PA was 13 ± 12 min with 162 mg and 7 ± 3 min with 650 mg ASA (p=NS). VN correlated with AA-induced PA (r = 0.80, p < .001) and serum TxB2 levels (r = 0.76, p < .001). 95% inhibition of serum TxB2 was achieved at 38 ± 22 min and 22 ± 8 min with the 162 and 650 mg ASA, respectively (p = .08). The onset and extent of the antiplatelet effect of 650 mg ASA is numerically faster and greater than the 162 mg dose. VN identifies the onset, extent, and dose response to ASA therapy. The ease of using VN should facilitate multicenter PD investigations of ASA.
Aspirin (acetylsalicylic acid) is an important drug widely used to prevent adverse ischemic events in patients with cardiovascular disease. Platelet aggregation and thromboxane B2 levels in blood samples by complex laboratory methods are used to assess platelet response to aspirin. VerifyNow assay is a simple laboratory test that has not been used to assess the immediate effect of aspirin. In this study, conducted in 10 healthy volunteers, we compared the immediate platelet response to aspirin by serially assessing platelet aggregation by aggregometry and VerifyNow assay, and thromboxane B2 levels. We also measured plasma levels of acetylsalicylic acid and salicylic acid. Our study demonstrated that the VerifyNow Aspirin test identifies the onset, extent, and dose-response to aspirin therapy. The ease of using the VerifyNow test should facilitate multicenter pharmacodynamic investigations of aspirin.
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Aspirina , Inhibidores de Agregación Plaquetaria , Humanos , Aspirina/farmacología , Aspirina/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacocinética , Agregación PlaquetariaRESUMEN
Administration of acetylsalicylic acid (ASA) at early stage after surgery for spontaneous intracerebral hemorrhage (SICH) may increase the risk of postoperative intracranial bleeding (PIB), because of potential inhibition of platelet function. This study aimed to investigate whether early ASA administration after surgery was related to increased risk of PIB. This retrospective study enrolled SICH patients receiving surgery from September 2019 to December 2022 in seven medical institution. Based on postoperative ASA administration, patients who continuously received ASA more than three days within seven days post-surgery were identified as ASA users, otherwise as non-ASA users. The primary outcome was symptomatic PIB events within seven days after surgery. Incidence of PIB was compared between ASA users and non-ASA users using survival analysis. This study included 744 appropriate patients from 794 SICH patients. PIB occurred in 42 patients. Survival analysis showed no statistical difference between ASA users and non-ASA users in incidence of PIB (P = 0.900). Multivariate Cox analysis demonstrated current smoker (hazard ratio [HR], 2.50, 95%CI, 1.33-4.71, P = 0.005), dyslipidemia (HR = 3.03; 95%CI, 1.31-6.99; P = 0.010) and pre-hemorrhagic antiplatelet therapy (HR = 3.05; 95% CI, 1.64-5.68; P < 0.001) were associated with PIB. Subgroup analysis manifested no significant difference in incidence of PIB between ASA users and non-ASA users after controlling the effect from factors of PIB (i.e., sex, age, current smoker, regular drinker, dyslipidemia, pre-hemorrhagic antiplatelet therapy and hematoma location). This study revealed that early ASA administration to SICH patients after surgery was not related to increased risk of PIB.
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Aspirina , Hemorragia Cerebral , Inhibidores de Agregación Plaquetaria , Humanos , Masculino , Femenino , Aspirina/efectos adversos , Aspirina/administración & dosificación , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Hemorragia Posoperatoria/epidemiología , Factores de Riesgo , Adulto , Hemorragias Intracraneales/epidemiologíaRESUMEN
Secondary prevention of patients with chronic coronary syndrome is based on the long-term use of a single anti-aggregating drug which is traditionally represented by acetylsalicylic acid (ASA) in light of the results of studies and meta-analyses which have demonstrated a clear anti-ischaemic efficacy against of an acceptable increase in the risk of bleeding, especially intracranial and gastrointestinal bleeding. The availability of drugs such as clopidogrel, which inhibits platelet activity through the P2Y12 receptor pathway, has called into question this paradigm, also in consideration of the fact that the scientific evidence that supports the use of ASA in secondary prevention is based on dated studies with some limitations. Over the last few years, randomized trials have demonstrated how clopidogrel has an efficacy profile comparable to that of ASA and a safety profile that is sometimes even better. In light of the new evidence, it is therefore legitimate to ask whether in this clinical scenario, ASA should still be considered the drug of choice or whether clopidogrel could represent the preferable alternative.
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OBJECTIVES: Early assessment of pregnant individuals for risk of preterm preeclampsia (PE) is possible at the 11-14 week ultrasound visit using a validated multiple marker algorithm, allowing timely use of preventative low-dose acetylsalicylic acid (LDA) in high-risk patients. With no established early screening program for preterm PE in Canada, our objectives were to assess the acceptability and operational impact of routine screening for preterm PE during the 11-14 week ultrasound visit, evaluate uptake and adherence to LDA when recommended, and assess screening performance. METHODS: A prospective implementation study of preterm PE screening among pregnant patients at the ultrasound unit of a tertiary obstetric centre in Toronto, Canada. RESULTS: A total of 1057 patients were screened, with an acceptance rate of 87.1%. First-trimester ultrasound appointment time increased by a median time of 7 minutes (Interquartile range 6-9). By 16 weeks gestation, 88.7% of high-risk patients had started LDA, with adherence of 88.7%â94.6% from 16â36 weeks. Satisfaction with counselling was ≥7/10 in more than 95% of patients. There were 7 cases of preterm PE (0.73%), 3 in the low-risk group (0.35%), and 4 in the high-risk group (4.1%). When accounting for LDA use, the treatment-adjusted detection rate was 78.6%. CONCLUSIONS: We demonstrate successful implementation of a validated, effective screening and prevention program for preterm PE as a first step in the implementation of a broader program adaptable for cultural, access/equity considerations, and marker availability.
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Preeclampsia , Embarazo , Recién Nacido , Femenino , Humanos , Preeclampsia/diagnóstico , Preeclampsia/prevención & control , Preeclampsia/tratamiento farmacológico , Estudios Prospectivos , Aspirina/uso terapéutico , Primer Trimestre del Embarazo , Factores de Riesgo , Biomarcadores , Factor de Crecimiento Placentario , Arteria UterinaRESUMEN
Gastric ulcers affect approx. 10% of population. Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (ASA) predispose to or impair the physiologically complex healing of pre-existing ulcers. Since H2S is an endogenous cytoprotective molecule, we hypothesized that new H2S-releasing ASA-derivative (ATB-340) could overcome pathological impact of NSAIDs on GI regeneration.Clinically translational gastric ulcers were induced in Wistar rats using state-of-the-art microsurgical model employing serosal application of acetic acid. This was followed by 9 days long i.g. daily treatment with vehicle, ATB-340 (6-24 mg/kg) or equimolar ASA doses (4-14 mg/kg). Ulcer area was assessed macro- and microscopically. Prostaglandin (PG)E2 levels, indicating pharmacological activity of NSAIDs and 8-hydroxyguanozine content, reflecting nucleic acids oxidation in serum/gastric mucosa, were determined by ELISA. Qualitative and/or quantitative pathway-specific alterations at the ulcer margin were evaluated using real-time PCR and mass spectrometry-based proteomics.ASA, unlike ATB-340, dose-dependently delayed/impaired gastric tissue recovery, deregulating 310 proteins at the ulcer margin, including Ras signalling, wound healing or apoptosis regulators. ATB-340 maintained NSAIDs-specific cyclooxygenase-inhibiting capacity on systemic and GI level but in time-dependent manner. High dose of ATB-340 (24 mg/kg daily), but not ASA, decreased nucleic acids oxidation and upregulated anti-oxidative/anti-inflammatory heme oxygenase-1, 24-dehydrocholesterol reductase or suppressor of cytokine signalling (SOCS3) at the ulcer margin.Thus, ASA impairs the physiological healing of pre-existing gastric ulcers, inducing the extensive molecularly functional and proteomic alterations at the wound margin. H2S-releasing ATB-340 maintains the target activity of NSAIDs with limited impact on gastric PGE2 signalling and physiological GI regeneration, enhancing anti-inflammatory and anti-oxidative response, and providing the pharmacological advantage.
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Antiinflamatorios no Esteroideos , Aspirina , Mucosa Gástrica , Sulfuro de Hidrógeno , Proteómica , Ratas Wistar , Úlcera Gástrica , Cicatrización de Heridas , Animales , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismo , Aspirina/farmacología , Ratas , Proteómica/métodos , Sulfuro de Hidrógeno/metabolismo , Sulfuro de Hidrógeno/farmacología , Masculino , Cicatrización de Heridas/efectos de los fármacos , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Antiinflamatorios no Esteroideos/farmacología , Dinoprostona/metabolismo , Enfermedad Crónica , Relación Dosis-Respuesta a Droga , Modelos Animales de Enfermedad , Naproxeno/análogos & derivadosRESUMEN
Compound L-36, a new derivative of 6H-1,3,4-thiadiazine, was studied in in vitro and in vivo experiments. This compound exhibits high antiplatelet and antithrombogenic activity. In in vitro experiments, compound L-36 by its antiplatelet activity (by IC50) was superior to acetylsalicylic acid by 9.4 times. In in vivo experiments, compound L-36 by its ED50 value was close to the comparison drug. On the model of pulmonary artery thrombosis, compound L-36 ensured better survival of experimental animals than acetylsalicylic acid. Morphological studies showed that compound L-36 effectively attenuated the thrombosis processes in the pulmonary tissue induced by intravenous injection of a thrombogenic mixture (epinephrine and collagen).
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Aspirina , Fibrinolíticos , Inhibidores de Agregación Plaquetaria , Agregación Plaquetaria , Tiadiazinas , Animales , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/química , Tiadiazinas/farmacología , Tiadiazinas/química , Fibrinolíticos/farmacología , Fibrinolíticos/química , Agregación Plaquetaria/efectos de los fármacos , Aspirina/farmacología , Masculino , Trombosis/tratamiento farmacológico , Trombosis/prevención & control , Ratas , Arteria Pulmonar/efectos de los fármacos , Colágeno , Epinefrina/farmacología , Ratones , Plaquetas/efectos de los fármacosRESUMEN
BACKGROUND: Although acetylsalicylic acid has been widely used for decades to treat and prevent various diseases, its potential effects on endometrial receptivity and subsequent pregnancy rates are still controversial due to conflicting data: many reports have shown positive effects of acetylsalicylic acid, whereas others have found that it has no effect. Furthermore, the direct effects of acetylsalicylic acid on various functions of normal endometrial cells, especially endometrial stem cells, and their underlying molecular mechanisms have not yet been proven. Recently, studies have revealed that a reduced number of active stem/progenitor cells within endometrial tissue limits cyclic endometrial regeneration and subsequently decreases pregnancy success rates, suggesting that endometrial stem cells play a critical role in endometrial regeneration and subsequent endometrial receptivity. METHODS: We assessed whether aspirin treatment can inhibit various endometrial stem cell functions related to regenerative capacity, such as self-renewal, migration, pluripotency/stemness, and differentiation capacity, in vitro. Next, we evaluated whether SERPINB2 regulates the effects of aspirin on endometrial stem cell functions by depleting SERPINB2 expression with specific shRNA targeting SERPINB2. To further investigate whether aspirin also inhibits various endometrial stem cell functions in vivo, aspirin was administered daily to mice through intraperitoneal (i.p.) injection for 7 days. RESULTS: In addition to its previously identified roles, to the best of our knowledge, we found for the first time that acetylsalicylic acid directly inhibits various human endometrial stem cell functions related to regenerative capacity (i.e., self-renewal, migration, differentiation, and capacity) through its novel target gene SERPINB2 in vitro. Acetylsalicylic acid exerts its function by suppressing well-known prosurvival pathways, such as Akt and/or ERK1/2 signaling, through a SERPINB2 signaling cascade. Moreover, we also found that acetylsalicylic acid markedly inhibits regenerative capacity-related functions in endometrial stem cells within tissue. CONCLUSIONS: We have found that acetylsalicylic acid has diverse effects on various endometrial stem cell functions related to regenerative capacity. Our findings are a critical step toward the development of more effective therapeutic strategies to increase the chances of successful pregnancy. Video Abstract.
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Aspirina , Células Madre , Embarazo , Femenino , Animales , Ratones , Humanos , Aspirina/farmacología , Aspirina/metabolismo , Endometrio/metabolismo , Transducción de Señal , Diferenciación CelularRESUMEN
INTRODUCTION: Microvascular thrombosis with resultant flap loss remains a devastating complication in autologous breast reconstruction. While acetylsalicylic acid (ASA) for prevention of microvascular thrombosis is commonly administered postoperatively, clinical evidence supporting this practice remains insufficient. Here, we investigate the association of postoperative ASA administration with differences in clinical outcomes following microsurgical breast reconstruction. METHODS: A prospectively maintained database was queried to identify patients who had undergone microsurgical breast reconstruction. Patients were categorized based on whether they had received postoperative ASA for 30 d (Group 1) or had not received ASA (Group 2). Patient demographics, reconstructive outcomes, complications, and transfusion requirements were retrieved. RESULTS: One hundred thirty six patients with a mean age of 49.5 y and a mean body mass index of 28.5 kg/m2 who had undergone a total of 216 microsurgical breast reconstructions were included. No significant differences were noted with regard to patient demographics with the exceptions of increased rates of neoadjuvant chemotherapy and delayed reconstruction in Group 1. There were no significant differences in the rates of postoperative complications including breast hematoma, mastectomy skin flap necrosis, partial flap necrosis, seroma, and deep venous thrombosis between patients who did or did not receive ASA postoperatively. Similarly, no difference was noted regarding postoperative blood transfusion rates (Group 1: 9.9% versus Group 2: 9.1%; P = 0.78). Finally, patients in Group 1 had significantly longer hospital stays (Q1 = 4, median = 4.5, Q3 = 5). CONCLUSIONS: Postoperative ASA administration is not associated with improved postoperative clinical outcomes. The use of ASA routinely after autologous breast reconstruction does not appear to be a necessity in practice.
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Neoplasias de la Mama , Mamoplastia , Trombosis , Humanos , Persona de Mediana Edad , Femenino , Mastectomía/efectos adversos , Aspirina/efectos adversos , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/complicaciones , Mamoplastia/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Trombosis/complicaciones , Necrosis , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIMS: It is well known that elevated cholesterol is associated with enhanced platelet aggregation and patients suffering from familial hypercholesterolemia (FH) have a high risk of thrombotic cardiovascular events. Although decreasing cholesterol level is associated with attenuation of platelet hyperactivity, there are currently no data on the effect of convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9ab) on platelet reactivity in FH. The aim of the study was to analyse the impact of different therapies including PCSK9ab on platelet aggregation in FH. METHODS: This study enrolled all 15 patients treated in the University Hospital Hradec Králové for FH. PCSK9ab have been administered in 12 of 15 patients while 8 patients were also undergoing lipid apheresis. Blood samples from all patients including pre- and post-apheresis period were tested for platelet aggregation triggered by 7 inducers, and the effect of 3 clinically used drugs (acetylsalicylic acid, ticagrelor and vorapaxar) was compared as well. RESULTS: Although apheresis decreased the reactivity of platelets in general, platelet responses were not different between non-apheresis patients treated with PCSK9ab and apheresis patients (post-apheresis values) with the exception of ristocetin. However, when compared to age-matched healthy population, FH patients had significantly lower platelet aggregation responses to 4 out of 7 used inducers and higher profit from 2 out of 3 used antiplatelet drugs even after exclusion of FH patients regularly receiving conventional antiplatelet treatment. CONCLUSION: This study showed for the first time the suitability of PCSK9ab treatment for reduction of platelet reactivity in FH patients.
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OBJECTIVES: To investigate the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for pre-eclampsia in a Danish population and compare screening performance with that of the current Danish strategy, which is based on maternal risk factors. METHODS: This was a prospective study of women with a singleton pregnancy attending for their first-trimester ultrasound scan and screening for aneuploidies at six Danish university hospitals between May 2019 and December 2020. Prenatal data on maternal characteristics and medical history were recorded, and measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum pregnancy-associated plasma protein-A (PAPP-A) and serum placental growth factor (PlGF) were collected without performing a risk assessment for pre-eclampsia. Information on acetylsalicylic acid use was recorded. After delivery, pregnancy outcome, including gestational age at delivery and pre-eclampsia diagnosis, was recorded. Pre-eclampsia risk assessment for each woman was calculated blinded to outcome using the FMF screening algorithm following adjustment to the Danish population. Detection rates (DRs) of the FMF algorithm were calculated for a fixed screen-positive rate (SPR) of 10% and for the SPR achieved in the current Danish screening. RESULTS: A total of 8783 pregnant women were included, with a median age of 30.8 (interquartile range (IQR), 28.1-33.9) years. The majority were white (95%), naturally conceiving (90%), non-smokers (97%) and had no family history of pre-eclampsia (96%). The median body mass index was 23.4 (IQR, 21.2-26.6) kg/m2 . A complete risk assessment including maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A was available for 8156 women (92.9%). In these women, UtA-PI was measured bilaterally with a median value of 1.58 (IQR, 1.27-1.94) and the median resting MAP of 80.5 (IQR, 76.1-85.4) mmHg in two consecutive measurements. Among these, 303 (3.7%) developed pre-eclampsia, including 55 (0.7%) cases of pre-eclampsia with delivery < 37 weeks of gestation and 16 (0.2%) cases of pre-eclampsia with delivery < 34 weeks. At a SPR of 10%, combined screening using the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A had a DR of 77.4% (95% CI, 57.6-97.2%) for pre-eclampsia with delivery < 34 weeks, 66.8% (95% CI, 54.4-79.1%) for pre-eclampsia with delivery < 37 weeks and 44.1% (95% CI, 38.5-49.7%) for pre-eclampsia with delivery at any gestational age. The current Danish screening strategy using maternal risk factors detected 25.0% of women with pre-eclampsia with delivery < 34 weeks and 19.6% of women with pre-eclampsia with delivery < 37 weeks at a SPR of 3.4%. When applying the FMF algorithm including maternal characteristics, MAP, UtA-PI and PlGF at the fixed SPR of 3.4%, the DRs were 60.5% (95% CI, 36.9-84.1%) for PE with delivery < 34 weeks and 45.2% (95% CI, 32.0-58.5%) for PE with delivery < 37 weeks. CONCLUSION: In this large Danish multicenter study, the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A predicted 77.4% of cases with pre-eclampsia with delivery < 34 weeks and 66.8% of cases with pre-eclampsia with delivery < 37 weeks of gestation at a SPR of 10%, suggesting that the performance of the algorithm in a Danish cohort matches that in other populations. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Preeclampsia , Diagnóstico Prenatal , Embarazo , Femenino , Humanos , Preeclampsia/epidemiología , Estudios Prospectivos , Proteína Plasmática A Asociada al Embarazo , Factor de Crecimiento Placentario , Presión Arterial , Arteria Uterina/diagnóstico por imagen , Biomarcadores , Flujo Pulsátil , Dinamarca/epidemiologíaRESUMEN
BACKGROUND: Encephalomyocarditis virus (EMCV) has been isolated from many animals, frequently as the cause of fatal myocarditis, but pigs are the most susceptible domestic specie. The virus was isolated in swine farms since 1958 in Panama and Europe from cases of sudden death in young pigs, and the main origin of outbreaks has been assumed to be local rodent populations. There is no treatment for the disease. CASE PRESENTATION: The clinical case describes an outbreak of encephalomyocarditis virus in a farrowing (farm A) and a weaning (farm B) site, with mortality that reached 24.2% in suckling piglets and 7.7% in weaners. The farms were located in an endemic Italian area, and the outbreak was characterised by high mortality with sudden death and clinical signs due to heart failure (trembling, dispnea and fever). The rodents control program was the key action in managing the outbreak. However, in the weaning site, the lack of rodent program in some unexplored areas of the barn (false ceiling) was responsible of a longer time of resolution of the outbreak. An unusual support treatment approach from human medicine suggestion was also applied using acetylsalicylic acid for its antiphlogistic and antithrombotic effects. CONCLUSIONS: To control the rodent population in a pig farm is often difficult and requires a deep knowledge also of the rodents habits. Considering the lack of treatment for the disease and the absence of available vaccines in several Countries, acetylsalicylic acid might be of interest for further studies as an important support for pigs' recovery.
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Virus de la Encefalomiocarditis , Enfermedades de los Porcinos , Humanos , Animales , Porcinos , Granjas , Brotes de Enfermedades/veterinaria , Italia/epidemiologíaRESUMEN
The use of acetylsalicylic acid (ASA) is problematic in subjects with histories of hypersensitivity reactions (HRs) to it or with cross-reactive types of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. We sought to evaluate the efficacy of low-dose ASA challenge (LDAC) and desensitization to allow ASA therapy at an antiplatelet dose in patients with atherosclerotic cardiovascular disease (ASCVD) or multiple related risk factors and histories of HRs to ASA or ≥ 2 chemically unrelated NSAIDs. We studied prospectively all patients with such histories and ≥ 3 risk factors for ASCVD (group I), chronic coronary syndrome (CCS, group II), and acute coronary syndrome (ACS) with indication for ASA desensitization (group III). Patients from groups I and II underwent LDACs (cumulative dose of 110 mg), while those from group III were desensitized (cumulative dose of 100.1 mg). We evaluated 103 patients: 62 from group I, 24 from group II, and 17 from group III. Eighty-two of the 86 patients from the first two groups underwent LDACs and 2 reacted. Subsequently, 22 (27.5%) of the 80 patients with negative LDACs were administered dual antiplatelet therapy with ASA after successful percutaneous coronary interventions, thus sparing desensitizations. The remaining 4 patients with CCS and all 17 patients from group III were successfully desensitized. In this pragmatic study, LDAC proved to be a safe and reliable diagnostic tool for identifying patients with histories of HRs to ASA or ≥ 2 different NSAIDs who can tolerate ASA at antiplatelet doses. Routine LDAC is advisable in all patients at high risk for ASCVD or with CCS who report HRs to ASA or ≥ 2 NSAIDs. ASA desensitization remains a safe and effective option in patients with ACS. Study flow-chart. ASCVD atherosclerotic cardiovascular disease; CCS chronic coronary syndrome; ACS acute coronary syndrome; ASA acetylsalicylic acid; DAPT dual antiplatelet therapy; PCI percutaneous coronary intervention; NSAIDs nonsteroidal anti-inflammatory drugs; NERD NSAID-exacerbated respiratory disease; NECD NSAID-exacerbated cutaneous disease; NIUAA NSAID-induced urticaria-angioedema or anaphylaxis; SNIUAA single NSAID-induced urticaria-angioedema or anaphylaxis; SNIDHR single NSAID-induced delayed hypersensitivity reaction.