Administration Of Acetylsalicylic Acid Research Articles

Evaluation of the antinociceptive activities of natural propolis extract derived from stingless bee Trigona thoracica in mice.

: Stingless bee propolis is a popular traditional folk medicine and has been employed since ancient times. This study aimed to evaluate the antinociceptive activities of the chemical constituents of aqueous propolis extract (APE) collected by Trigona thoracica in a nociceptive model in mice. : The identification of chemical constituents of APE was performed using high-performance liquid chromatography (HPLC). Ninety-six male Swiss mice were administered APE (400 mg/kg, 1,000 mg/kg, and 2,000 mg/kg) before developing nociceptive pain models. Then, the antinociceptive properties of each APE dose were evaluated in acetic acid-induced abdominal constriction, hot plate test, and formalin-induced paw licking test. Administration of normal saline, acetylsalicylic acid (ASA, 100 mg/kg, orally), and morphine (5 mg/kg, intraperitoneally) were used for the experiments. : HPLC revealed that the APE from Trigona thoracica contained p-coumaric acid (R2 = 0.999) and caffeic acid (R2 = 0.998). Although all APE dosages showed inhibition of acetic acid-induced abdominal constriction, only 2,000 mg/kg was comparable to the result of ASA (68.7% vs. 73.3%, respectively). In the hot plate test, only 2,000 mg/kg of APE increased the latency time significantly compared to the control. In the formalin test, the durations of paw licking were significantly reduced at early and late phases in all APE groups with a decrease from 45.1% to 53.3%. : APE from Trigona thoracica, containing p-coumaric acid and caffeic acid, exhibited antinociceptive effects, which supports its potential use in targeting the prevention or reversal of central and peripheral sensitization that may produce clinical pain conditions.

Initial intravenous immunoglobulin therapy without aspirin for acute Kawasaki disease: a retrospective cohort study with a Bayesian inference

ObjectiveTo clarify the necessity of acetylsalicylic acid (ASA) administration combined with intravenous immunoglobulin (IVIG) therapy in the treatment of acute Kawasaki disease.DesignRetrospective cohort study.SettingMulticentre.ParticipantsThis study included 735 patients with Kawasaki...

Efficacy and Safety of Extended Antithrombotic Therapy in Stable Coronary Artery Disease: Systematic Review of the Literature

Extended dual antithrombotic therapy, which entails the concurrent administration of acetylsalicylic acid and a P2Y12 inhibitor or anticoagulant beyond the initial 12 months of presenting with acute coronary syndrome, has been the subject of considerable research in recent years. The objective of this study was to evaluate the impact of dual antithrombotic therapy in stable coronary artery disease. We conducted a registered (PROSPERO CRD42023394771) assessing the safety and efficacy of antithrombotic therapy published over the past 20 years up to May 2021 in four databases (PubMed, EMBASE, BVSalud /LILACS, Cochrane Reviews). Using the RoB2 tool, we evaluated the risk of bias. We performed a literature search using keywords and identified 95 eligible articles, of which 23 were excluded as duplicates. After applying the inclusion and exclusion criteria, we found 29 articles for a detailed review and assessment of bias by applying the ROB2 toll, and we found that five articles had a low risk of bias. Our analysis found that extended dual antithrombotic therapy reduces ischemic cardiovascular outcomes, but it comes at the cost of an increased risk of bleeding when compared with acetylsalicylic acid monotherapy.

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.

Left External Iliac Artery Aneurysm in horse – Case report

An aneurysm is defined as the abnormal and localized dilation of a blood vessel, which can be congenital or acquired. The main consequence is vessel rupture, leading to hemorrhage, hypovolemic shock, and subsequent sudden death. Clinical signs can also be silent or resemble other pathologies, making the diagnosis complex. This study aims to report the clinical case of a Criollo mare diagnosed with an aneurysm of the left external iliac artery, as well as the treatment and diagnostic methods. During the anamnesis, it was observed that the patient experienced episodes of acute abdominal discomfort with rapid and spontaneous resolution, anorexia, and progressive weight loss for approximately a year. Musculoskeletal evaluation revealed grade III lameness in the left pelvic limb. Rectal palpation revealed a parasagittal increase in volume near the lumbosacral segment with a palpable pulse in the region of the left abdominal aorta. Rectal ultrasound with a linear probe (5.5 MHz) revealed decreased and retrograde blood flow compared to the contralateral vessel, suggesting an aneurysm of the left external iliac artery. The prescribed treatment involved the administration of acepromazine, omeprazole, and acetylsalicylic acid for 90 days. Ultrasonography was essential for the final diagnosis and resolution of the reported case, along with the combination of drugs described in the therapeutic protocol.

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.

Abstract 13963: Redefining the Assessment of “Therapeutic” Platelet Response to Acetylsalicylic Acid

Background: Despite extensive investigations, the optimal assessment of the “therapeutic response” to acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between serum thromboxane (Tx)B 2 ; arachidonic acid (AA)-induced platelet aggregation (PA) by light transmittance aggregometry (LTA); aspirin reaction units (ARU) by VerifyNow aspirin test (VN), and pharmacokinetics (PK). Methods: Serial PD and PK analyses were performed immediately after a single 162 or 650 mg dose of chewed and swallowed ASA in ten healthy volunteers. ASA response was defined as &gt;95% inhibition of serum TxB 2, &lt;550 ARU by VN test and ≤20% AA-induced PA. Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. Results: ASA Response measured by VN, and AA-induced PA was achieved within 30 minutes of ASA administration. A good correlation was observed between VN ARU and 1 mM AA-induced maximum PA (r=0.80, p&lt;0.001), serum TxB 2 (r=0.76, p&lt;0.001), and inhibition of serum TxB 2 (r=0.87, p&lt;0.001). The relation between platelet aggregation and TxB 2 inhibition appears to be dichotomous, with only modest inhibition of TxB 2 (~50% inhibition) associated with marked inhibition of platelet aggregation. ROC curve analyses indicated that ≤558 ARU and ≤7% AA-induced PA were associated with &gt;95% inhibition of TxB 2 . A plasma ASA 686 ng/mL cut-off was associated with &gt;95% inhibition of serum TxB 2 , ≤7% 1 mM AA-induced PA by LTA, and ≤585 ARU. Conclusion: Our study demonstrated an important relationship between PD and PK parameters measured immediately following oral ASA and cutoff values for VN assay and LTA that is associated with &gt;95% inhibition of serum TxB 2 . We demonstrated that ~50% inhibition of TxB 2 is required to reach high levels of platelet function inhibition.

Traumatic Carotid Artery Dissection — A Case Report

AbstractTraumatic carotid artery dissection (TCAD) usually occurs after a direct cervical trauma or blunt trauma that causes hyperextension and excessive rotation of the neck. The most frequent presentation of TCAD is stroke, with 80% of patients developing a stroke in the first week after the trauma. Recent data indicate that symptoms start later in non-survivors (19.5 hours after trauma) compared with survivors (12.5 hours). In this case report, a young boy, 14 years-old, developed TCAD after he fell from his bike. He developed ischemic stroke symptomatology in the eighth day of hospitalization, with full recovery of symtoms after acetylsalicylic acid (AAS) administration. The use of antithrombotic medication is recommended, aiming for better neurological outcomes and prevention of stroke in TCAD patients, as highlighted by our case. However, the treatment recommendations are based on observational studies and expert opinion, owing to the lack of concrete data on the treatment of carotid artery blunt trauma. New studies and data are required to improve diagnosis and treatment of TCAD.

ASA Allergy and Desensitization Protocols in the Management of CAD: A Review of Literature.

Acetylsalicylic acid (ASA) hypersensitivity still represents one of the major deals for patients with atherosclerotic cardiovascular disease (ASHD), especially for those requiring percutaneous coronary interventions in the absence of validated alternative options. Despite symptoms after ASA administration being reported in 6-20% of cases, true ASA allergy only represents a minority of the patients, pointing to the importance of challenge tests and potential strategies for tolerance induction. ASA desensitization protocols were proposed several decades ago, with accumulating the literature on their use in patients undergoing PCI either for chronic disease or acute coronary syndromes. Nevertheless, the promising results of the studies and meta-analyses have not been validated so far by the support of large-scale randomized trials or unique indications from guidelines. Therefore, ASA desensitization is still largely unapplied, leaving the management of ASA hypersensitivity to the individualized approach of cardiologists.

Determination of milk concentrations and pharmacokinetics of salicylic acid following acetylsalicylic acid (aspirin) administration in postpartum dairy cows

The objectives of this descriptive study were to 1) describe the pharmacokinetics of salicylic acid (SA) in the milk and plasma of postpartum dairy cattle following oral administration of ace­tylsalicylic acid (ASA) (aspirin); 2) to estimate a recommended milk withdrawal period for dairy cattle treated with ASA; and 3) to determine the impact of ASA administration on plasma prostaglandin E2 metabolite (PGEM) concentrations. Adminis­tration of non-steroidal anti-inflammatory drugs, such as the widely available drug aspirin, or acetylsalicylic acid (ASA), may improve health and milk production in postpartum dairy cows. However, plasma pharmacokinetic data for salicylic acid (SA), the active metabolite of ASA, are unrepresentative of lactating dairy cows and current treatment regimens, and there are cur­rently no published milk residue and minimal pharmacody­namic data available for ASA or SA in dairy cows.

Acute Chest Pain—Diagnostic Accuracy and Pre-hospital Use of Anticoagulants and Platelet Aggregation Inhibitors.

Acute chest pain (aCP) can be a symptom of life-threatening diseases such as acute coronary or aortic syndrome; however, aCP often is not of cardiac origin. The current recommendations for pre-hospital drug treatment in patients with aCP are unclear. We conducted a retrospective cohort study of 822 patients with aCP who were treated by emergency physicians (EP). The causes of aCP were classified as follows: non-ST-segment elevation acute coronary syndrome (NSTE-ACS), acute aortic syndrome, hypertensive crisis, cardiac arrhythmia, musculoskeletal causes, and other causes. The suspected diagnoses on admission were compared with the discharge diagnoses, and the pre-hospital administration of acetylsalicylic acid (ASA) and unfractionated heparin (UFH) was analyzed. It was also investigated which parameters improved diagnostic accuracy. The positive predictive value of diagnosis by an EP was 39.7%. NSTE-ACS was the most common suspected diagnosis (74.7%), but was confirmed in the hospital in only 26.3% of cases. ASA was administered in 51%, UFH in 55%, and both drugs in 46.4% of cases. Many patients whose in-hospital diagnosis was not NSTE-ACS had been treated with anticoagulants before their arrival in the hospital: ASA in 62.9% of cases, UFH in 66.0%, and both in 56.5%. Despite low pre-hospital diagnostic accuracy, ASA and UFH are often given to patients with acute chest pain who are treated by EPs before their arrival in the hospital. The pre-hospital measurement of hsTrop-T might help differentiate NSTE-ACS from other causes of acute chest pain. This is important, because current guidelines do not provide clear recommendations for the pre-hospital pharmacotherapy of NSTE-ACS.

Abstract 6124: Recombinant apurinic/apyrimidinic endonuclease-1/redox factor-1 plus acetylsalicylic acid combination therapy inhibits tumorigenesis in an orthotopic xenograft murine model of triple-negative breast cancer

Abstract Triple-negative breast cancer (TNBC) is characterized with hormone receptor negative and frequently exhibits inherently aggressive clinical behavior, resulting in poor prognoses. TNBCs are highly heterogenic, leading to obstacles in identifying new therapeutic targets and performing targeted therapy. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1), a multifunctional protein, is mainly involved in DNA repair and redox regulation; it is upregulated in various cancers and is extracellularly secreted because of hyperacetylation. We previously reported that hyperacetylation induced APE1/Ref-1 release causes apoptosis in TNBCs. In the current study, we aimed to assess the therapeutic efficacy of combination treatment involving recombinant human APE1/Ref-1 (rhAPE1/Ref-1) plus acetylsalicylic acid (ASA) in TNBC xenograft mice. ASA co-treatment was used to induce and lasting acetylation of rhAPE1/Ref-1. For in vivo analysis, we constructed an orthotopic xenograft in vivo model of TNBC by using MDA-MB-231 cells. We performed combination therapy involving intravenous injection of purified rhAPE1/Ref-1 (1 mg/kg) and oral administration of ASA (20 mg/kg) thrice a week for 6 weeks in TNBC xenograft mice. This rhAPE1/Ref-1 plus ASA combination therapy inhibited tumor formation and growth, without damaging liver or kidney tissue, and decreased plasma levels of the cancer marker CEA and breast cancer-specific markers CA27-29 and CA15-3 in the TNBC xenograft mice. The TNBC group, which underwent combination therapy, had more apoptotic cells and greater inflammatory cell infiltration in tumor tissues than the vehicle group did. Additionally, in tumor tissue of TNBC with combination therapy exhibits increased apoptosis following upregulation of Bax, cleaved-caspase-3, and cleaved-PARP. Thus, we found that rhAPE1/Ref-1 plus ASA combination therapy enhanced antitumor effects in TNBCs via inflammatory cell infiltration and apoptosis signaling pathways. Our findings indicate the therapeutic potential of rhAPE1/Ref-1 plus ASA combination therapy for TNBC. Citation Format: Yu Ran Lee, Hee Kyoung Joo, Eun-Ok Lee, Sungmin Kim, Hao Jin, Yeon Hee Choi, Eun Ju Choi, Byeong Hwa Jeon. Recombinant apurinic/apyrimidinic endonuclease-1/redox factor-1 plus acetylsalicylic acid combination therapy inhibits tumorigenesis in an orthotopic xenograft murine model of triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6124.

Acetylsalicylic Acid Is Not Associated With Improved Clinical Outcomes After Microsurgical Breast Reconstruction

IntroductionMicrovascular 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. MethodsA 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. ResultsOne 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). ConclusionsPostoperative 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.

Protective Effect of Irsogladine against Aspirin-Induced Mucosal Injury in Human Induced Pluripotent Stem Cell-Derived Small Intestine

Background and Objectives: Acetylsalicylic acid (ASA) is widely used for preventing cerebrovascular and cardiovascular diseases. Gastrointestinal (GI) tract injury is one of the major complications of aspirin use, potentially leading to severe GI bleeding. However, no drugs for preventing aspirin-induced small intestinal injury have been developed. The aim of this study was to establish a human experimental model for investigating aspirin-induced small intestinal mucosal injury. In addition, we evaluated the protective effect of Irsogladine against aspirin-induced small intestinal mucosal injury using human induced pluripotent stem cell-derived 2D monolayer crypt-villus structural small intestine (2D-hiPSC-SI). Materials and Methods: Human iPS cell-derived intestinal organoids were seeded and cultured in Air-liquid interface. The permeability of 2D-hiPSC-SI was evaluated using Lucifer yellow. Changes in structure and mucosal permeability of 2D-hiPSC-SI after addition of aspirin were confirmed over time, and changes in intestinal epithelium-related markers were evaluated by real-time qPCR and Immunofluorescence staining. The effect of Irsogladine on prevention of aspirin mucosal injury was examined by adding Irsogladine to the culture medium. Results: Cultured 2D-hiPSC-SI showed multi-lineage differentiation into small intestinal epithelium comprised of absorptive cells, goblet cells, enteroendocrine cells, and Paneth cells, which express CD10, MUC2, chromogranin A, and lysozyme, respectively. RNA in situ hybridization revealed intestinal stem cells that express Lgr5. ASA administration induced an increase in the mucosal permeability of 2D-hiPSC-SI. ASA-injured 2D-hiPSC-SI showed decreased mRNA expression of multi-lineage small intestinal cell markers as well as intestinal stem cell marker Lgr5. Administration of Irsogladine on the basal side of the 2D-hiPSC-SI resulted in significant increases in Mki67 and Muc2 mRNA expression by 2D-hiPSCs at 48 h compared with the control group. Administration of 400 µg/mL Irsogladine to the ASA-induced small intestinal injury model resulting in significantly decreased mucosal permeability of 2D-hiPSC-SI. In immunofluorescence staining, Irsogladine significantly increased the fluorescence intensity of MUC2 under normal conditions and administration of 400 µg/mL ASA. Conclusions: we established a novel ASA-induced small intestinal injury model using human iPSC-derived small intestine. Irsogladine maintains mucosal permeability and goblet cell differentiation against ASA-induced small intestinal injury.

Hypothetical interventions on emergency ambulance and prehospital acetylsalicylic acid administration in myocardial infarction patients presenting without chest pain

BackgroundMyocardial infarction (MI) patients presenting without chest pain are a diagnostic challenge. They receive suboptimal prehospital management and have high mortality. To elucidate potential benefits of improved management, we analysed expected outcome among non-chest pain MI patients if hypothetically they (1) received emergency ambulances/acetylsalicylic acid (ASA) as often as observed for chest pain patients, and (2) all received emergency ambulance/ASA.MethodsWe sampled calls to emergency and non-emergency medical services for patients hospitalized with MI within 24 h and categorized calls as chest pain/non-chest pain. Outcomes were 30-day mortality and a 1-year combined outcome of re-infarction, heart failure admission, and mortality. Targeted minimum loss-based estimation was used for all statistical analyses.ResultsAmong 5418 calls regarding MI patients, 24% (1309) were recorded with non-chest pain. In total, 90% (3689/4109) of chest pain and 40% (525/1309) of non-chest pain patients received an emergency ambulance, and 73% (2668/3632) and 37% (192/518) of chest pain and non-chest pain patients received prehospital ASA. Providing ambulances to all non-chest pain patients was not associated with improved survival. Prehospital administration of ASA to all emergency ambulance transports of non-chest pain MI patients was expected to reduce 30-day mortality by 5.3% (CI 95%: [1.7%;9%]) from 12.8% to 7.4%. No significant reduction was found for the 1-year combined outcome (2.6% CI 95% [− 2.9%;8.1%]). In comparison, the observed 30-day mortality was 3% among ambulance-transported chest pain MI patients.ConclusionsOur study found large differences in the prehospital management of MI patients with and without chest pain. Improved prehospital ASA administration to non-chest pain MI patients could possibly reduce 30-day mortality, but long-term effects appear limited. Non-chest pain MI patients are difficult to identify prehospital and possible unintended effects of ASA might outweigh the potential benefits of improving the prehospital management. Future research should investigate ways to improve the prehospital recognition of MI in the absence of chest pain.

Determination of milk concentrations and pharmacokinetics of salicylic acid following acetylsalicylic acid (aspirin) administration in postpartum dairy cows.

The objectives of this descriptive study were to (1) describe the pharmacokinetics of salicylic acid (SA) in the milk and plasma of postpartum dairy cattle following oral administration of acetylsalicylic acid (ASA; aspirin), (2) to estimate a recommended milk withdrawal period for dairy cattle treated with ASA, and (3) to determine the effect of ASA administration on plasma prostaglandin E2 metabolite (PGEM) concentrations. Primiparous (n = 3) and multiparous (n = 7) postpartum Holstein dairy cows received 2 oral treatments with ASA at 200 mg/kg of body weight, 24 h apart. Concentrations of SA in plasma and milk from 0 h through 120 h after ASA administration were analyzed using ultra performance liquid chromatography triple quadrupole mass spectrometry and a milk withdrawal period was estimated using the United States Food and Drug Administration Milk Discard App in R. Two withdrawal periods were estimated: (1) a whole-herd treatment scenario with no dilution factor and (2) an individual animal treatment scenario with a bulk tank factor included in analysis. Plasma PGEM concentrations in samples from 0 h to 24 h after ASA administration were determined using a commercially available competitive ELISA. Milk SA concentrations were undetected in all cows by 48 h after the last ASA treatment. Secondary peaks were observed in plasma at 58 and 82 h after the last treatment and in milk at 87 h after the last treatment. In the absence of a tolerance for SA in milk, the estimated milk withdrawal periods were (1) 156 h for the whole-herd treatment scenario and (2) 120 h for the individual animal treatment scenario. Plasma PGEM concentrations were reduced compared with baseline for up to 12 h after ASA administration, with the greatest reduction observed at 2 h. Results from this study suggest that the current milk withhold recommendation for dairy cattle administered ASA may need revision to 120 h (5 d) and that ASA administration may mitigate postpartum inflammation through reduction in prostaglandin production for up to 12 h after treatment. Pharmacokinetic and milk withdrawal data from this study will inform future recommendations for extra-label use of aspirin in postpartum dairy cows. Further research is required to determine the basis for the secondary SA peaks and to elucidate the long-term effects of ASA administration on dairy cow health.

ИЗМЕНЕНИЕ ПОКАЗАТЕЛЕЙ ЭЛЕКТРОКАРДИОГРАММЫ КРЫС ПОД ВЛИЯНИЕМ АЦЕТИЛСАЛИЦИЛОВОЙ КИСЛОТЫ И ЕЕ КОМПЛЕКСНЫХ СОЕДИНЕНИЙ С МЕТАЛЛАМИ

The effect of acetylsalicylic acid (ASA) and its complex compounds with cobalt, zinc, nickel and manganese met- als at doses of 5, 10 and 20 mg/kg on the electrocardiographic parameters of rats was studied. It was shown that after administration of ASA and the tested salicylates to animals in all the studied doses, there was a statistically significant increase in the duration of the QRS complex relative to the values of this indicator in the control group of animals, most pronounced after administration of cobalt salicylate at a dose of 20 mg/kg both relative to the values of this indicator in the control group and in animals treated with ASA. The analysis of the duration of the QT interval also showed an increase in this indicator in animals of all groups, but the most pronounced after the introduction of manganese salicy- late. It was found that the tested salicylates have not only more pronounced, but often qualitatively new cardiotropic effects compared to ASA.

Platelet function testing using the Multiplate analyzer after administration of aspirin in Aachen minipigs.

Knowledge of platelet function in pigs and the effectiveness of antiplatelet therapy is important to ensure proper transferability from animal studies to humans. Our aim was to (1) characterize baseline platelet function of Aachen minipigs using the bedside Multiplate analyzer, (2) compare baseline platelet function with Göttingen minipigs, and (3) characterize platelet inhibition within the first 5 minutes after intravenous administration of acetylsalicylic acid (ASA). We characterized the baseline platelet function and hematological parameters in 9 Aachen minipigs. Historical data of 8 unmedicated Göttingen minipigs were used for comparison of baseline values. Platelet inhibition in Aachen minipigs was tested 1–5 minutes after intravenous administration of 500 mg ASA. Multiplate examinations included the following tests: ASPI test (to assess the effect of ASA), adenosine-diphosphate-test (ADP test) and thrombin receptor activating peptide test (TRAP test). Median values and interquartile range (IQR) of the Multiplate baseline tests in Aachen minipigs were as follows: ASPI: 39 U (IQR = 21–71), ADP: 70 U (IQR = 48–73), and TRAP: 8 U (IQR = 6–9), whereas the values in Göttingen minipigs were as follows: ASPI: 70.5 U (IQR = 60–78), ADP: 51 U (IQR = 45–66), and TRAP: 6.5 U (IQR = 4–8). ASPI values of Göttingen minipigs were significantly higher than those of Aachen minipigs (p = 0.046). Intravenous administration of ASA in Aachen minipigs resulted in significant platelet inhibition after 1 minute, which remained stable over a period of 5 minutes (p≤0.038). Aachen minipigs appeared to have a high variance in arachidonic acid-mediated platelet aggregation. In Aachen minipigs, intravenous ASA administration resulted in immediate platelet inhibition.

Personalized allocation of acetylsalicylic acid therapy for secondary prevention of coronary artery disease.

BackgroundA single-daily dose of 75 mg of acetylsalicylic acid inhibits 100% of thromboxane-B2 synthesis within 30–60 min. Thromboxane-B2 synthesis then recovers slowly as new platelets are released from the bone marrow. Normally, only 10% of the platelets are replaced daily by new platelets entering circulation. Hence, 24 h after a dose of acetylsalicylic acid, thromboxane-B2 synthesis is still suppressed by more than 90%. Hence, there is an adequate anti-platelet effect even after 24 h of acetylsalicylic acid intake. However, some patients treated with once-daily acetylsalicylic acid may have an incomplete 24-h suppression of thromboxane-B2 synthesis due to increased platelet turnover. The response could be improved in such patients by twice-daily acetylsalicylic acid administration. This study aimed to identify such a group of patients who would benefit from a twice-daily dose of acetylsalicylic acid.Materials and methodsSerum thromboxane-B2 levels were measured in 79 patients with coronary artery disease receiving 75 mg of acetylsalicylic acid for secondary prophylaxis. Serum levels of thromboxane-B2 were measured after 4 and 24 h of acetylsalicylic acid intake. Patients were then classified into three groups: steady suppression group (serum thromboxane B2 is adequately suppressed at 4 and 24 h), i.e., adequate response to acetylsalicylic acid; fast recovery group (more than 10% rise in serum thromboxane-B2 levels at 24-h when compared to at 4-h) and non-responders (serum thromboxane-B2 levels of >3,100 pg/ml after 4 h of acetylsalicylic acid intake). Patients in the fast recovery group were given twice-daily acetylsalicylic acid and thromboxane-B2 levels were re-measured.ResultsA total of 20 patients (24.3%) had steady suppression of thromboxane-B2 and 11 patients (13.9%) belonged to the fast recovery group, i.e., thromboxane-B2 levels were adequately suppressed at 4 h but had recovered by more than 10% at 24 h; which was adequately suppressed by twice-daily acetylsalicylic acid (p 0.004). A total of 48 patients (60.8%) were non-responders.ConclusionTwice-daily acetylsalicylic acid may be beneficial if serum thromboxane-B2 levels at 4 h are <3,100 and >3,100 pg/ml at 24 h. If thromboxane-B2 levels at 4 and 24 h is <3100 pg/ml but if there is a >10% rise in serum thromboxane B2 at 24 h as compared to that at 4 h, then twice-daily acetylsalicylic acid should be considered. However, if thromboxane-B2 at 4 and 24 h is >3,100 pg/ml consider switching over to a P2Y12 inhibitor.

Exacerbation risk of Shortened and Prolonged Administration of Acetylsalicylic Acid on the Lipid Profile of Wistar Rats

Exacerbation risk of Shortened and Prolonged Administration of Acetylsalicylic Acid on the Lipid Profile of Wistar Rats