Doses Of Acetylsalicylic Acid Research Articles

Physiological healing of chronic gastric ulcer is not impaired by the hydrogen sulphide (H2S)-releasing derivative of acetylsalicylic acid (ATB-340): functional and proteomic approaches.

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 ofpre-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 (6-24mg/kg) or equimolar ASA doses (4-14mg/kg). Ulcer area was assessed macro- and microscopically. Prostaglandin (PG)E2 levels,indicating pharmacological activity of NSAIDsand 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 (24mg/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, andproviding the pharmacological advantage.

Synergistic effects of omega-3 polyunsaturated fatty acids and aspirin in the clinical practice – a narrative review

Abstract The review aimed to illustrate the structure, role and effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) in combination with acetylsalicylic acid (aspirin, ASA) in various clinical cases. This verification of earlier single studies may be a guide in the further treatment of civilization diseases. The results of the presented narrative review suggest that aspirin supplementation with omega-3 fatty acids reduces pro-inflammatory biomarkers in sepsis and acute respiratory distress syndrome. Including adequate amounts of omega 3-PUFAs in therapy, rather than increasing the dose of acetylsalicylic acid, may contribute to beneficial effects in treating thrombosis and preventing myocardial infarction or other cardiovascular diseases, which is particularly important in aspirin-resistant patients. As suggested in the literature, a low daily dose of omega-3 fatty acids was effective in slowing the progression of kidney disease with IgA nephropathy. Aspirin supplementation with omega-3 fatty acids has improved clinical and immunological outcomes in the treatment of periodontitis or the therapy of colorectal cancer tumor lesions. The synergistic effect of both compounds is proposed as a new therapeutic option in the treatment of Parkinson’s disease. Further research into the synergistic effects of omega-3 fatty acids in combination with acetylsalicylic acid may provide a breakthrough in drug dose reduction, ultimately enabling more effective and safer pharmacotherapy for the patient. Therefore, studies on polyunsaturated fatty acids in combination with nonsteroidal anti-inflammatory drugs in vivo are needed.

Angiotensin converting enzyme inhibitors related cough and associated medications

Introduction: Angiotensin-converting enzyme inhibitors (ACEi) are among the main anti-hypertensive medications. While they are generally well tolerated, dry cough is one of their important side effects, with a frequency of up to 10 percent. Medications that are associated with increased ACEi-related cough frequency are not well described. We wanted to evaluate medications that might have an effect on ACEi-related cough.
 Methods: This study was designed as a post-hoc analysis of our previously published study. Patients who were on ACEi were identified, and demographics, comorbidities, laboratory data, and medications were retrieved via electronic medical records. Patients who reported cough and whose cough ceased after ACEi withdrawal were defined as having an "ACEi-related cough." Patients were grouped according to their ACEi-related cough presence.
 Results: One hundred and twenty-one patients were included in the study, of whom 14 experienced ACEi-related coughs. All medications except for low-dose acetylsalicylic acid (ASA) and calcium channel blockers (CCB) were similar between the groups. Low-dose ASA use was significantly higher among patients who experienced ACEi-related cough (50% vs. 16.8%, p = 0.04). On the other hand, CCB use was associated with lower ACEi-related cough (7.7% vs. 35.5%, p = 0.03). Medications other than ASA and CCB, demographics, comorbidities, and laboratory data were similar across the groups.
 Discussion: ACEi-related cough risk is higher among patients on low-dose ASA and lower among patients on CCB. Further studies are needed to demonstrate if there is a “safe” acetylsalicylic acid dose that is not associated with ACEi-related cough.

Early assessment of the pharmacokinetic and pharmacodynamic effects following acetylsalicylic acid loading: toward a definition for acute therapeutic response.

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 650mg 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 30min 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. 686ng/ml plasma ASA cut-off point was associated with > 95% inhibition of serum TxB2, ≤ 7% 1mM AA-induced PA, and ≤ 585 ARU. A modest ~ 50% inhibition of TxB2 inhibition was associated with marked inhibition of 1mM 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.

Variability of the antithrombotic effect of acetylsalicylic acid with the administration of different dosages: reality or myth?

Abstract Introduction We rely on the antithrombotic effect of acetylsalicylic acid (ASA) in a number of pathologies, although other beneficial effects are known, such as its anti-inflammatory properties, when administered in higher doses (500mg, 1000mg per os). However, whether the anti-inflammatory effect decreases the antithrombotic potency of ASA is not known. This gap in evidence may lead to an unnecessary use of two drugs (one antithrombotic and one anti-inflammatory) that could be replaced by ASA alone. This scenario presents frequently: post-infarct pericarditis or when in doubt between non-ST segment elevation myocardial infarction vs myopericarditis. In such cases, the use of ASA could assure both antithrombotic and anti-inflammatory effects. Since the antithrombotic effect of ASA is not scientifically proved for higher doses, currently we use ASA 100mg as an antithrombotic agent and ibuprofen as an anti-inflammatory. This experimental study intends to assess whether ASA maintains its antithrombotic effect when administered in an anti-inflammatory dose. Methods Twenty healthy volunteers were recruited. They all had their platelet function assessed in a qualitative manner, using PFA-200 Innovance technology. The volunteers were randomized into four groups, with 5 participants each. The participants of groups 1, 2, 3 and 4 ingested ASA 100mg, 300mg, 500mg and 1000mg respectively, in a blind experiment. One hour after ingestion (peak of action), the volunteers’ platelet function was reassessed. PFA-200 evaluates platelet function through platelet occlusion time (OT), which is measured in milliseconds (ms). Normal platelet function translates into OT of 82-150ms. If the OT is higher than 150ms, the patient is anti-aggregated. Results Prior to ASA administration, 19/20 volunteers had OT within the reference range. Afterwards, in all four groups, volunteers reached OT &amp;gt; 150ms, regardless of the ASA dose administered. Mean OT values for each group were 188ms [SD-23] , 205ms [SD-63], 262ms[SD-44] and 232ms [SD-47], respectively. Overall SD was 32ms. Conclusion ASA maintains its antithrombotic effect when administered in an anti-inflammatory dose. There is no clear correlation between the potency of antithrombotic effect and the ASA dose administered. This was a pilot study that supports the maintenance of the antithrombotic effect of ASA in higher doses, but further and larger studies are required to corroborate these results.

Acetylsalicylic acid as the only pharmacological method for the prevention of preeclampsia: A retrospective study

Background. Preeclampsia (PE) complicates 28% of pregnancies worldwide, negatively impacting the pregnant woman and the fetus. Therefore, its prevention remains relevant. It is believed that the cause of PE, especially early PE, is a placentation disorder. It warrants studying drugs that can improve placenta development. The leadership in this matter is maintained by acetylsalicylic acid, which, according to the ASPRE study, reduced the incidence of PE at 34 weeks of pregnancy by 82%. The use of low molecular weight heparins (LMWH), dipyridamole, and antioxidants for PE prevention remains controversial and continues to be studied by foreign and Russian scientists.&#x0D; Aim. To assess the efficacy of acetylsalicylic acid, LMWH, dipyridamole (Curantyl), and bovine blood derivates (Actovegin) in the Russian population of pregnant women at high risk for PE prevention.&#x0D; Materials and methods. The study included 244 patients. We reviewed the archived case records of 103 patients diagnosed with severe PE, who delivered in 2019 at the State Clinical Hospital №24, and 141 pregnant women from the Maternity clinic №3 at the Veresaev Moscow State Clinical Hospital, where the risk of PE was assessed as high, according to the results of extended combined screening of the first trimester of pregnancy. Eighty-nine pregnant women received acetylsalicylic acid at a dose of 75 mg and 54 at a dose of 150 mg. In addition, 22 patients received LMWH, 6 dipyridamole, and 3 Actovegin. The absolute risks, the risk ratio, and statistical significance when taking drugs in each risk group were calculated to assess the efficacy of acetylsalicylic acid and other drugs for PE prevention in the above risk groups.&#x0D; Results. The resulting weak inverse correlation (r=-0.31) between the PE severity at delivery and the dose of acetylsalicylic acid indicates that an increase in the acetylsalicylic acid dose was associated with a decrease in the PE severity. The effectiveness of combinations of various drugs for PE prevention was assessed by analyzing factor correspondences. Two-dimensional scaling of the most likely combinations showed that most patients received acetylsalicylic acid in the high-risk group with no PE. Additional use of LMWH, Curantyl, and Actovegin did not reduce the risk of PE.&#x0D; Conclusion. Acetylsalicylic acid is the only pharmaceutical method for preventing PE in high-risk groups. Higher doses of acetylsalicylic acid are associated with lower PE severity.

Rapid desensitization to acetylsalicylic acid in patients with ischemic heart disease: 10-year experience of a portuguese allergy department.

Introduction. Managing Acetylsalicylic Acid (ASA) hypersensitivity (HS) in patients with ischemic heart disease (IHD) is a challenge. Data on Rapid Desensitization (RD) to ASA is scarce. We aimed to report the outcomes of our 10-year experience with RD to ASA. Methods. Retrospective, observational, single-center study of patients with ASA HS and suspected IHD who underwent RD to ASA between March 2009 and February 2019. Results. Fifty patients were included. ASA HS presentation ranged from urticaria (56%) to anaphylaxis (32%). Regarding cardiologic diagnoses, 40 patients (80%) had acute coronary syndrome and 10 (20%) stable angina. The majority of patients (N = 36.72%) underwent percutaneous coronary intervention. RD to ASA was successful in all patients. Two patients presented a mild HS reaction during the RD, which was promptly treated, and subsequent daily doses of ASA 100 mg were tolerated. Conclusions. In our cohort, RD to ASA in patients with ASA HS and IHD was very effective and safe.

The effects on clinical outcomes of administering medications together or separately in prolonged dual antiplatelet therapy after peripheral revascularisation.

In the current guidelines, dual antiplatelet therapy [acetylsalicylic acid (ASA) + clopidogrel] is recommended for at least three months after peripheral iliac stenting. In this study, we investigated the effect on clinical outcomes of adding ASA in different doses and at different times after peripheral revascularisation. Seventy-one patients were administered dual antiplatelet therapy after successful iliac stenting. Group 1, consisting of 40 patients, was given 75 mg of clopidogrel plus 75 mg of ASA in a single dose in the morning. In group 2, separate doses of 75 mg of clopidogrel (in the morning) and 81 mg of 1 × 1 ASA (in the evening) were started in 31 patients. The demographic data and bleeding rates of the patients after the procedure were recorded. The groups were found to be similar in terms of age, gender and accompanying co-morbid factors (p > 0.05). The patency rate was 100% in the first month in both groups, and it was above 90% at the sixth month. When one-year patency rates were compared, although the first group had higher rates (85.3%), no significant difference was found (p < 0.05). However, there were 10 (24.4%) bleeding events in group 1, and five (12.2%) of these were in the gastrointestinal system, resulting in reduced haemoglobin levels (p = 0.038). ASA doses of 75 mg or 81 mg did not affect one-year patency rates. However, higher bleeding rates were observed in the group that received both clopidogrel and ASA treatment simultaneously (in the morning) despite the lower dose of ASA.

#5268 PREGNANCY OUTCOMES IN DIALYSIS PATIENTS: A TEN-YEAR SERIES FROM A TERTIARY CENTER

Abstract Background and Aims Pregnancy in dialysis patients was almost prohibited a decade ago, as fetal and maternal outcomes were very poor. In the last years, there has been a paradigm shift, as the introduction of intensive hemodialysis (HD) schedules has been associated with an impressive improvement on fetal outcomes, making motherhood a possibility in these women. Nevertheless, pregnancy in women on dialysis remains associated with a high incidence of complications and is extremely demanding for both patients and clinicians. We describe the maternal, obstetric, and perinatal outcomes of pregnancies in women on dialysis followed at the Nephro-Obstetric Clinic at Centro Hospitalar Universitário Lisboa Norte (CHULN). Method Retrospective analysis of pregnancies in women on dialysis and surveilled at the Nephro-Obstetric Clinic at CHULN from 2011 to 2022. Results We considered 17 pregnancies from 16 women. One of the women accounted was submitted to voluntary termination of pregnancy. Mean age was 31.5 ± 6.1 years; 70.6% were Black (n = 11) and 29.4% (n = 5) Caucasian; 58.8% were nulliparous (n = 10). All patients had chronic hypertension (HTN), although only 75.0% were under therapy (12/16). Additionally, 3/16 patients had diabetes and 2/16 hyperthyroidism. The mean of overall renal replacement therapy (RRT) duration was 9.1 ± 8.2 years (dialysis and renal transplantation time), being on dialysis program 43.7 ± 37.5 months before gestation. One patient was on peritoneal dialysis (PD) and two patients started HD during pregnancy. Five patients (31.2%) were exposed to teratogenic drugs during gestation. Pregnancy diagnosis occurred at 13.4 ± 5.6 weeks; 70.6% of the patients were on low dose acetylsalicylic acid (n = 12). HD mean time per week according to each trimester was 13.7 ± 2.8 hours/week, 24.5 ± 7.3 hours/week and 28.0 ± 8.0 hours/week during the 1st/2nd/3rd respectively. Mean pre-dialysis urea was 62.1 ± 28.0 mg/dL during gestation. Regarding maternal outcomes, worsening HTN occurred in 62.5% (n = 10) of patients during the 1st (4/10) and 2nd trimester (7/10) and pre- eclampsia (PE) occurred in 6/16 patients (1 with HELLP syndrome). One patient developed polyhydramnios and another one cholestasis of pregnancy. Premature rupture of membranes (PRM) occurred in 3 patients (at 17, 25 and 36 weeks); One patient asked for medical termination of pregnancy due to severe growth restriction and oligohydramnios at 20 weeks. Stillbirth occurred in 4 gestations (cervical insufficiency in a twin pregnancy, severe congenital fetal cardiopathy in a patient with PE, severe growth restriction and premature rupture of membranes (PRM). In the 2 patients with early PRM, the neonates died in the following week due to severe prematurity complications. Labor was induced in 9 patients, mainly due to PE (7/9). Cesarean was performed in 10/17 patients and mean gestation age at delivery was 29.8 ± 6.6 weeks. Extreme prematurity (&amp;lt;28 weeks) occurred in 3 pregnancies and there were three term babies. Mean birth weight was 1554.0±613.6 grams with 4 newborns having extremely low birth weight (&amp;lt;1000g) and 6 requiring neonatal care. Conclusion Our study reveals that pregnancy in women on dialysis is challenging and still associated with significant maternal, obstetric and perinatal complications. This population was highly heterogenous, with a significant number of patients living under unfavorable social conditions, and with significant comorbidities. The diagnosis of pregnancy took place mainly during the 2nd trimester, preventing early initiation of intensive dialysis schedules which could have significantly improved outcomes. Pregnancy planning, early diagnosis and management by a multidisciplinary experienced team are of paramount importance to improve outcomes and reduce complications.

Low-Dose Aspirin after ASPRE—More Questions Than Answers? Current International Approach after PE Screening in the First Trimester

Preeclampsia (PE) is a multi-factorial disorder of pregnancy, and it continues to be one of the leading causes of fetal and maternal morbidity and mortality worldwide. Aspirin is universally recommended for high-risk women to reduce preeclampsia risk. The purpose of this review is to summarize the recommendations of various scientific societies on predicting preeclampsia and their indications for the inclusion of acetylsalicylic acid (ASA) prophylaxis. Fourteen guidelines were compared. The recommended dose, screening method, and gestational age at the start of the test vary depending on the recommendation. The societies are inclined to recommend using increasingly higher doses (&gt;75 mg) of ASA, with many encouraging doses from 100 mg upward. Most societies indicate that the optimal time for implementing aspirin is prior to 16 weeks’ gestation. Following the publication of the Aspirin for Evidence-Based Preeclampsia Prevention (ASPRE) trial results and other papers evaluating the Fetal Medicine Foundation (FMF) screening model, a large number of societies have changed their recommendations from those based on risk factors alone to the ones based on the risk assessment proposed by the FMF. This allows for the detection of a high-risk pregnancy population in whom aspirin will be remarkably effective in preventing preterm PE, thereby decreasing maternal and fetal morbidity.

Complications and outcomes of pregnancy in patients with antiphospholipid antibodies during various treatment methods

Introduction. Antiphospholipid antibodies (APAs) exert multifaceted effects on the course of pregnancy by disrupting microcirculation, affecting the hemostasis, as well as damaging the endothelial membranes, leading to early reproductive loss and development of placenta-associated complications depending on the affected gestation stage. Planning and management of pregnancy in women in the absence of criteria for complete antiphospholipid syndrome (APS) currently remains unresolved issue. The absence of generally accepted treatment standards for this category of patients and inability to substantiate the diagnosis according to the APS classification criteria complicate selection of therapeutic tactics.Aim: to conduct a comparative analysis of therapy-based complications and outcomes of pregnancy in APA carriers.Materials and Methods. During the period 2019–2021 a prospective study of 150 patients who entered pregnancy with aggravated obstetric and gynecological history, serum APA level was examined. Considering the risks of developing obstetric and thrombotic complications, all patients were prescribed prophylactic doses of low molecular weight heparins (LMWHs) and low doses of acetylsalicylic acid (ASA). The patients were divided into 3 groups using a random number generator. Group 1 (n = 50), in addition to the prescribed LMWH (enoxaparin sodium 40 mg 1 time per day) and ASA (150 mg 1 time per day), also underwent plasmapheresis (PF) 4 sessions per 1 course in 6–8, 12–14 and 22–24 weeks of pregnancy; group 2 (n = 50) received courses of intravenous immunoglobulins (IVIG) at a course dose of 300 ml (15 g) simultaneously; group 3 (n = 50) received no additional therapies. Rate of pregnancy complications was comparatively assessed – development of fetal growth retardation (FGR), low birth weight fetus, gestational arterial hypertension (AH), moderate and severe preeclampsia (PE), anemia and delivery outcomes.Results. It was found that in group 3 there was a higher incidence of gestational hypertension (p2,3 &lt; 0.0001), moderate PE (p 1,3 =0.071; p 2,3 = 0.0019), low weight fetus for gestational age (p2,3 = 0.0002) and FGR (p2,3 = 0.003). In group 1, compared with group 2, there were more often observed small weight for gestational age fetus (p1,2 = 0.018) and FGR (p1,2 = 0.024), gestational hypertension (p1,2 = 0.0008), anemia (p1,2 &lt; 0.0001) and latent iron deficiency (p1,2 &lt; 0.0001). Also, groups 2 and 3 vs. group 1 were more likely to have intrahepatic cholestasis during pregnancy (p1,2 = 0.013; p1,3 = 0.003).Conclusion. In the group of patients receiving complex therapy consisting of LMWHs prophylactic doses, low ASA doses and IVIG courses, the risks of developing placenta-associated complications and iron deficiency were reduced compared to other groups indicating about a higher efficiency of this therapy regimen. However, the development of intrahepatic cholestasis during pregnancy was less common in the group of patients receiving PF courses, in contrast to using IVIG courses, which can be accounted for by additional effect of efferent therapeutic methods and should be taken into account in a differentiated approach for management of patients with liver and gallbladder pathology.

P396 FIBRINOUS PERICARDITIS AND STILL’S DISEASE IN ADULTHOOD: A RARE AND INSIDIOUS COMBINATION

Abstract In 9/2022 we admitted a 69–year–old man with history of hypertension, in therapy with bisoprolol and edoxaban after recent diagnosis of persistent atrial fibrillation, with a minor pericardial effusion at the echocardiogram. He had dyspnea, fever, and atrial fibrillation with elevated cardiac frequency. The echocardiogram showed increased pericardial effusion, circumferential, about 2 cm, with important fibrinous organization, without signs of cardiac tamponade (fig1). Hemocultures and urocultures were repeatedly negative, with significant increase in flogosis parameters. Therapy with high–dose acetylsalicylic acid was started first and then Ibruprofene + colchicine with poor clinical response and persistence of symptoms and effusion. The presence of elevated fever, arthralgias, transient skin rush to the trunk and flogosis indices (CRP 17 mg/dl, ESR 97mm, WBC 11000/ul with 80% neutrophil, ferritin 2200 ng/ml), with negativity of antinucleus antibodies and rheumatoid factor, allowed to place diagnosis of adult Still’s disease (AOSD). High–dose steroid therapy (prednisone 1mg/kg) was initiated with fever regression, progressive normalization of inflammatory indices and spontaneous restoration of sinus rhythm. The 7–day echocardiogram showed almost complete resolution of pericardial fibrinous effusion (fig 2). At 2 months patient remained asymptomatic, no more pericardial effusion, no signs of flogosis. Differential diagnosis of pericarditis is often complex, and therapeutic attitude and prognosis are variable according to etiology. AOSD has a prevalence of about 1/100,000, affects mainly young adults, very late onset cases are rare. Transient, small, salmon–pink, not itchy rashes, usually concurrent with fever, can drive diagnosis, along with major and minor criteria of Yamaguchi. Often patients have serositic involvement with pleuritis or pericarditis, with tamponade needing drainage. Such forms respond well only to steroid treatment. However, cases of fibrinous pericarditis as marked as the one described have not been described; the so important fibrinous component would made an eventual pericardiocentesis difficult. Although infrequent, it is a differential diagnosis that the cardiologist must consider in cases of refractory pericarditis and pericardial effusion.

Low dose acetyl salicylic acid (LDA) mediates epigenetic changes in preeclampsia placental mesenchymal stem cells similar to cells from healthy pregnancy

IntroductionPreeclampsia (PE) affects 2–8% of all pregnancies, and is the leading cause of maternal and fetal morbidity and mortality. We reported on pathophysiological changes in placenta mesenchymal stem cells (P-MSCs) in PE. P-MSCs can be isolated from different layers of the placenta at the interface between the fetus and mother. The ability of MSCs from other sources to be immune licensed as immune suppressor cells indicated that P-MSCs could mitigate fetal rejection. Acetylsalicylic acid (aspirin) is indicated for treating PE. Indeed, low-dose aspirin is recommended to prevent PE in high risk patients. MethodsWe conducted robust computational analyses to study changes in gene expression in P-MSCs from PE and healthy term pregnancies as compared with PE-MSCs treated with low dose acetyl salicylic acid (LDA). Confocal microscopy studied phospho-H2AX levels in P-MSCs. ResultsWe identified changes in >400 genes with LDA, similar to levels of healthy pregnancy. The top canonical pathways that incorporate these genes were linked to DNA repair damage - Basic excision repair (BER), Nucleotide excision repair (NER) and DNA replication. A role for the sumoylation (SUMO) pathway, which could regulate gene expression and protein stabilization was significant although reduced as compared to BER and NER pathways. Labeling for phopho-H2AX indicated no evidence of double strand break in PE P-MSCs. DiscussionThe overlapping of key genes within each pathway suggested a major role for LDA in the epigenetic landscape of PE P-MSCs. Overall, this study showed a new insight into how LDA reset the P-MSCs in PE subjects around the DNA.

EGFR and MMP-9 are associated with neointimal hyperplasia in systemic-to-pulmonary shunts in children with complex cyanotic heart disease

Systemic-to-pulmonary shunt malfunction contributes to morbidity in children with complex congenital heart disease after palliative procedure. Neointimal hyperplasia might play a role in the pathogenesis increasing risk for shunt obstruction. The aim was to evaluate the role of epidermal growth factor receptor (EGFR) and matrix-metalloproteinase 9 (MMP-9) in the formation of neointimal within shunts. Immunohistochemistry was performed with anti-EGFR and anti-MMP-9 on shunts removed at follow-up palliative or corrective procedure. Whole-genome single-nucleotide polymorphisms genotyping was performed on DNA extracted from patients´ blood samples and allele frequencies were compared between the group of patients with shunts displaying severe stenosis (≥ 40% of lumen) and the remaining group. Immunohistochemistry detected EGFR and MMP-9 in 24 of 31 shunts, located mainly in the luminal area. Cross-sectional area of EGFR and MMP-9 measured in median 0.19 mm2 (IQR 0.1–0.3 mm2) and 0.04 mm2 (IQR 0.03–0.09 mm2), respectively, and correlated positively with the area of neointimal measured on histology (r = 0.729, p < 0.001 and r = 0.0479, p = 0.018, respectively). There was a trend of inverse correlation between the dose of acetylsalicylic acid and the degree of EGFR, but not MMP-9, expression within neointima. Certain alleles in epidermal growth factor (EGF) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were associated with increased stenosis and neointimal hyperplasia within shunts. EGFR and MMP-9 contribute to neointimal proliferation in SP shunts of children with complex cyanotic heart disease. SP shunts from patients carrying certain risk alleles in the genes encoding for EGF and TIMP-1 displayed increased neointima.

Limited effect of over-the-counter doses of ibuprofen on mechanisms regulating muscle hypertrophy during resistance training in young adults.

We have previously shown that maximal over-the-counter doses of ibuprofen, compared with low doses of acetylsalicylic acid, reduce muscle hypertrophy in young individuals after 8 wk of resistance training. Because the mechanism behind this effect has not been fully elucidated, we here investigated skeletal muscle molecular responses and myofiber adaptations in response to acute and chronic resistance training with concomitant drug intake. Thirty-one young (aged 18-35 yr) healthy men (n = 17) and women (n = 14) were randomized to receive either ibuprofen (IBU; 1,200 mg daily; n = 15) or acetylsalicylic acid (ASA; 75 mg daily; n = 16) while undergoing 8 wk of knee extension training. Muscle biopsies from the vastus lateralis were obtained before, at week 4 after an acute exercise session, and after 8 wk of resistance training and analyzed for mRNA markers and mTOR signaling, as well as quantification of total RNA content (marker of ribosome biogenesis) and immunohistochemical analysis of muscle fiber size, satellite cell content, myonuclear accretion, and capillarization. There were only two treatment × time interaction in selected molecular markers after acute exercise (atrogin-1 and MuRF1 mRNA), but several exercise effects. Muscle fiber size, satellite cell and myonuclear accretion, and capillarization were not affected by chronic training or drug intake. RNA content increased comparably (∼14%) in both groups. Collectively, these data suggest that established acute and chronic hypertrophy regulators (including mTOR signaling, ribosome biogenesis, satellite cell content, myonuclear accretion, and angiogenesis) were not differentially affected between groups and therefore do not explain the deleterious effects of ibuprofen on muscle hypertrophy in young adults.NEW & NOTEWORTHY Here we show that mTOR signaling, fiber size, ribosome biogenesis, satellite cell content, myonuclear accretion, and angiogenesis were not differentially affected between groups undergoing 8 wk of resistance training with concomitant anti-inflammatory medication (ibuprofen versus low-dose aspirin). Atrogin-1 and MuRF-1 mRNA were more downregulated after acute exercise in the low-dose aspirin group than in the ibuprofen group. Taken together it appears that these established hypertrophy regulators do not explain the previously reported deleterious effects of high doses of ibuprofen on muscle hypertrophy in young adults.

The effects of metformın, acetylsalıcylıc acıd and ıbuprofen on telomerase enzyme actıvıty: ınhıbıtory effect of ıbuprofen

Telomerase enzyme is necessary for the elongation of telomeres while telomerase being critical for aging and cancer. Metformin, ibuprofen, and acetylsalicylic acid used in this research are drugs that millions of people already use and that many are likely to use in future. In this study, the effects of these drugs on telomerase activity of Mus musculus swiss albino mice in liver tissue were investigated and the telomerase activity was measured with a PCR-ELISA based kit. In the study a possible connection between telomerase enzyme activity and activities of antioxidant enzymes was also investigated by determining the activity of superoxide dismutase (SOD) and catalase enzymes. The data obtained show that metformin slightly decreased telomerase enzyme activity in low dose application; however, this change was not statistically significant. In ibuprofen application, there was a significant inhibitory effect when high doses were used; whereas, there was a slight inhibitory effect at low doses. In acetylsalicylic acid application, a slight activator effect was detected; it was not statistically significant, though. Metformin was observed to increase catalase and SOD activities in general while low and high doses of acetyl salicylic acid showed different effects. In addition, ibuprofen caused a statistically significant increase in liver SOD values. It is important to note that this study demonstrated a significant inhibitory effect of ibuprofen on telomerase enzyme activity in animal models..

Monitoring the Antiplatelet Therapy Efficacy in Patients with Acute Ischemic Stroke.

Stroke is one of the leading causes of morbidity and mortality in populations of developed countries. Ischemic strokes account for 85 - 90% of all strokes, with the majority of strokes of non-cardioembolic pathogenesis. Platelet aggregation plays a key role in arterial thrombus formation. Therefore, effective antiplatelet therapy plays a key role in secondary prevention. Acetylsalicylic acid (ASA) is the main drug of choice, and clopidogrel therapy is another recommended treatment option. Monitoring of the efficacy of antiplatelet therapy has been intensively studied in patients with coronary artery disease in the context of coronary stent implantation. It is not yet part of the routine procedure in patients with stroke [1-3]. This study investigated the efficacy of antiplatelet therapy with ASA and clopidogrel using optical and impedance aggregometry in 42 consecutive patients with acute ischemic stroke. Patients were treated with throm-bolysis at baseline and platelet function was examined 24 hours after administration, focusing on the occurrence of platelet hyperaggregability and assessing the efficacy of any chronically administered antiplatelet therapy. Subsequently, patients were administered a loading dose of ASA or clopidogrel followed by a check of its efficacy 24 hours after administration. In the following days, the maintenance dose of the drug was continued and regular laboratory monitoring of treatment efficacy was performed every 24 hours. In patients with atherothrombotic stroke indicated for antiplatelet therapy, monitoring of residual platelet activity allowed for detection of potentially atrisk patients. These were 35% (9% borderline ineffective) of patients taking ASA and 55% (18% borderline ineffective) of patients treated with clopidogrel. The dose was adjusted, increased the administered treatment and no recurrence of stroke was observed in this study group at 1-year follow-up. Personalized antiplatelet therapy based on platelet function tests appears to be a useful method to reduce the risk of recurrent vascular events.

Asetil Salisilik Asit Solüsyonlarında Ön Çimlendirmenin Havuç Tohumlarının Tuz Stresi Altında Çimlenme ve Çıkışı Üzerine Etkileri

Bu araştırmada asetil salisik asit (ASA) solüsyonun farklı dozlarında ön çimlendirmenin “Nantes” havuç çeşidi (Daucus corata L.) tohumlarının tuz stresi altında çimlenme ve çıkış performansları üzerine etkileri laboratuar koşullarında araştırılmıştır. Tohumlar, ASA solüsyonları içerisinde 24 saat süreyle iklim dolabında ön çimlendirme işlemine tabi tutulmuştur. Bu işlemden sonra ön çimlendirme ve kontrol grubu olarak iki gruba ayrılmıştır. Her iki grup 0, 50, 100 ve 150 mM NaCl stresine maruz bırakılarak, ASA uygulamasının tuzluk sterine tepkileri incelenmiştir. Araştırma sonucunda yüksek tuz konsantrasyonunun (150 mM NaCl) havuç tohumlarının çimlenmesini azalttığı, yüksek dozdaki ASA ön uygulamalarının tohumların çimlenme ve çıkış parametrelerini etkilediği belirlenmiştir. Sonuçlara göre ön uygulamalar arasında doz x tuz interaksiyonunda 150 mg/L ASA uygulmasında 0 ve 50 mM NaCl interaksiyonunda %93 ile en yüksek çimlenme oranı belirlenmiştir. ASA uygulamalarının, düşük ve yüksek tuzluluğa sahip yetiştirme ortamlarında tohumların çimlenme oranında artış sağladığı ve başarılı bir şekilde kullanılabileceği ön görülmüştür.

The Effect of Low Doses of Acetylsalicylic Acid on the Occurrence of Rectal Aberrant Crypt Foci.

Background and Objectives: Aberrant crypt foci (ACF) are one of the earliest putative preneoplastic and, in some cases, neoplastic lesions in human colons. Many studies have confirmed the reduction of ACFs and colorectal adenomas after treatment with acetylsalicylic acid (ASA) commonly referred to as ASA; however, the minimum effective dose of ASA and the duration of use has not been fully elucidated. The objective of our study was to assess the significance of low dose ASA (75-mg internally once daily) to study the chemopreventive effect of ASA in ACF and adenomas development in patients taking this drug for a minimum period of 10 years. Materials and&amp;nbsp;Methods: Colonoscopy, combined with rectal mucosa staining with 0.25% methylene blue, was performed on 131 patients. The number of rectal ACF in the colon was divided into three groups: ACF &lt; 5; ACF 5-10; and ACF &gt; 10. Patients were divided into two groups: the "With ASA" group (the study group subjects taking ASA 75-mg daily for 10 years); and "Without ASA" group (control group subjects not taking ASA chronically). The incidence of different types of rectal ACF and colorectal polyps in both groups of subjects was analysed and ascertained. Results: Normal ACF was found in 12.3% in the study group vs. 87.7% control group, hyperplastic 22.4% vs. 77.6%, dysplastic 25% vs. 75%, mixed 0% vs. 100%. Treatment with ASA affects the occurrence of colorectal adenomas. The amount of dysplastic ACFs was lower in the study group than in the control group. The increase in dysplastic ACFs decreases with age in both groups, with the increase greater in those not taking ASA. Conclusions: Patients who take persistent, chronic (&gt;10 years) low doses of ASA have a lower total number of all types of rectal ACFs and adenomas compared to the control group.

70 Comparative study between PIMS and Kawasaki disease

BackgroundKawasaki disease (kDa) is a multisystemic vasculitis affecting medium and small vessels with a predilection for the coronary arteries. It appears to be very similar to the pediatric multisystemic inflammatory syndrome (PIMS), which is a post-infectious inflammatory condition occurring after SARS-COV2 infection. Although these two entities have clinical and biological similarities, marked differences are identified. The aim of this study is to compare the two conditions in order to highlight the specific criteria of each of these related entities and to describe their demographic, clinical, biological and therapeutic characteristics in our context.MethodSingle center prospective observational study from January 2021 to March 2022 was conducted, comparing children admitted for PIMS on the basis of persistent fever, inflammatory syndrome, and positive COVID-19 IgG serology to patients hospitalized for kDa according to American Heart Association criteria.Results42 cases were recruited, among them 24 PIMS and 18 kDa, with a male predominance. The average age was 5 years for PIMS and 2 years and 7 months for kDa. All had a persistant fever with an average duration of 8 days as reason for consultation. Conjunctivitis was found in 88% of kDa vs 75% of PIMS and cheilitis in 94% of kDa vs 75% of PIMS. Skin rash, extremity involvement, cervical adenopathy were reported in both pathologies with respective percentages of 62.5%, 17.4% and 25% for PIMS vs 61.1%, 33.3% and 33.3% for kDa. Abdominal pain was reported in 54.2% of PIMS patients vs 5.6% of kDa. All patients had an inflammatory syndrome. The mean sedimentation rate was 67 mm at the first h in PIMS and 99 mm at the first h in kDa. The mean CRP was 147 mg/l in PIMS vs 132 mg/l in kDa. Lymphopenia was predominant in PIMS with 33% vs 11% in kDa. Cardiac enzymes were higher in PIMS with 29% of myocarditis and 15% of coronary dilatation vs 16.7% of coronary involvement in kDa. All PIMS patients received immunoglobulin infusion IV-IG, corticosteroid therapy, and an antiplatelet agent, whereas patients with kDa received IV-IG and acetyl salicylic acid in anti-inflammatory doses. Apyrexia was obtained at day 1 of treatment in the majority of patients, whereas 5.6% of kDa had persistent aneurysm.ConclusionPIMS cases predominated over kDa cases during this pandemic period. The distinction between the two entities could be difficult given the clinico-biological similarities. Abdominal pain was significantly more frequent in PIMS patients, whereas lymphopenia and myocarditis were not. The prognosis was better in PIMS.