Benefits Of Acetylsalicylic Acid Research Articles

Anti-inflammatory activity of 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid in LPS-induced rat model

IntroductionSalicylic acid derivate is very popular for its activity to suppress pain, fever, and inflammation. One of its derivatives is acetylsalicylic acid (ASA) which has been reported repeatedly that, as a non-steroidal anti-inflammatory drug (NSAID), it has a cardioprotective effect. Although ASA has various advantages, several studies have reported that it may induce severe peptic ulcer disease. We recently synthesized a new compound derived from salicylic acid, namely 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid (3-CH2Cl) which still has the benefit of acetylsalicylic acid as an analgesic and antiplatelet, but lacks its harmful side effects (Caroline et al., 2019). In addition, in silico studies of 3-CH2Cl showed a higher affinity towards protein receptor cyclooxygenase-2 (COX-2; PDB: 5F1A) than ASA. We hypothesized that 3-CH2Cl inhibits the COX-2 activity which could presumably decrease the inflammatory responses. However, no knowledge is available on the anti-inflammatory response and molecular signaling of this new compound. Hence, in this study, we investigated the potential functional relevance of 3-CH2Cl in regulating the inflammatory response in lipopolysaccharide (LPS)-induced rats. The results of this study show that this compound could significantly reduce the inflammatory parameter in LPS-induced rats. Material and methodsRats were induced with LPS of 0.5 mg/kg bw intravenously, prior oral administration with vehicle (3% Pulvis Gummi Arabicum / PGA), 500 mg/60 kg body weight (bw; rat dosage converted to human) of 3-CH2Cl and ASA. The inflammatory parameters such as changes in the temperature of septic shock, cardiac blood plasma concentrations of IL-1β and TNF-α (ELISA), blood inflammation parameters, white blood cell concentrations, and lung histopathology were observed. Meanwhile, the stability of 3-CH2Cl powder was evaluated. ResultAfter the administration of 500 mg/60 kg bw of 3-CH2Cl (rat dosage converted to human) to LPS-induced rats, we observed a significant reduction of both TNF-α (5.70+/-1.04 × 103 pg/mL, p=<0.001) and IL-1β (2.32+/-0.28 × 103 pg/mL, p=<0.001) cardiac blood plasma concentrations. Besides, we found a reduction of white blood cell concentration and the severity of lung injury in the 3-CH2Cl group compared to the LPS-induced rat group. Additionally, this compound maintained the rat body temperature within normal limits during inflammation, preventing the rats to undergo septic shock, characterized by hypothermic (t = 120 min.) or hyperthermic (t = 360 min) conditions. Furthermore, 3-CH2Cl was found to be stable until 3 years at 25°C with a relative humidity of 75 ± 5%. Conclusion3-CH2Cl compound inhibited inflammation in the LPS-induced inflammation response model in rats, hypothetically through binding to COX-2, and presumably inhibited LPS-induced NF-κβ signaling pathways. This study could be used as a preliminary hint to investigate the target molecular pathways of 3-CH2Cl as a novel and less toxic therapeutical agent in alleviating the COX-related inflammatory diseases, and most importantly to support the planning and development of clinical trial.

Interactions between the Cyclooxygenase Metabolic Pathway and the Renin-Angiotensin-Aldosterone Systems: Their Effect on Cardiovascular Risk, from Theory to the Clinical Practice.

Coronary artery disease (CAD) and stroke are the most common and serious long-term complications of hypertension. Acetylsalicylic acid (ASA) significantly reduces their incidence and cardiovascular mortality. The RAAS activation plays an important role in pathogenesis of CVD, resulting in increased vascular resistance, proliferation of vascular-smooth-muscle-cells, and cardiac hypertrophy. Drugs acting on the renin-angiotensin-aldosterone system (RAAS) are demonstrated to reduce cardiovascular events in population with cardiovascular disease (CVD). The cyclooxygenase inhibitors limit the beneficial effect of RAAS-inhibitors, which in turn may be important in subjects with hypertension, CAD, and congestive heart failure. These observations apply to most of nonsteroidal anti-inflammatory drugs and ASA at high doses. Nevertheless, there is no strong evidence confirming presence of similar effects of cardioprotective ASA doses. The benefit of combined therapy with low-doses of ASA is—in some cases—significantly higher than that of monotherapy. So far, the significance of ASA in optimizing the pharmacotherapy remains not fully established. A better understanding of its influence on the particular CVD should contribute to more precise identification of patients in whom benefits of ASA outweigh the complication risk. This brief review summarizes the data regarding usefulness and safety of the ASA combination with drugs acting directly on the RAAS.

Standardised tomato extract as an alternative to acetylsalicylic acid in patients with primary hypertension and high cardiovascular risk - a randomised, controlled trial.

IntroductionCardiovascular (CV) diseases remain a leading global cause of death. It has been proven that the use of acetylsalicylic acid (ASA) in secondary prevention reduces the CV risk, while the benefits of ASA in primary prevention have recently been debated. The aim of the study was to compare the antiplatelet effect of standardised tomato extract (STE) and ASA in hypertensive patients with high CV risk.Material and methodsThe study involved high-risk patients with arterial hypertension (AH) randomly assigned to one of two groups: group 1 included 33 patients receiving ASA and group 2 included 32 patients receiving STE. The platelet aggregation was determined using the VerifyNow analyser.ResultsAfter 4 weeks of ASA treatment in group 1, a statistically significant reduction in aspirin reaction units (ARU) was observed (p < 0.001). However, the obese subgroup using ASA (n = 18) did not reveal a significant decrease in ARU (p > 0.05). After 4 weeks of STE treatment in the obese subgroup (n = 14), significant declines in ARU by 8.6% (95% CI: –19.5 to –1.7%; p < 0.05) and in P2Y12 reaction units (PRU) by 7.5% (95% CI: –17.6 to 1.8%; p < 0.05) were observed.ConclusionsThe antiplatelet effect of STE in hypertensive patients may be weight dependent. The group with AH and obesity might have potentially benefitted from STE treatment.

Acetylsalicylic Acid Exhibits Antitumor Effects in Esophageal Adenocarcinoma Cells In Vitro and In Vivo.

Recent observational studies have shown therapeutic benefits of acetylsalicylic acid (ASA) in several types of cancer. We examined whether ASA exerts antitumor activity in esophageal adenocarcinoma (EAC). Human EAC cells (OE33) were treated with ASA (0-5mM) to evaluate proliferation, apoptosis, and migration. In vivo model: OE33-derived tumors were subcutaneously implanted into athymic mice which were allocated to ASA (5 or 50mg/kg/day)/vehicle (5-6 animals/group). Tumor growth was assessed every 2-3days, and after 40days, mice were euthanized. Plasma drug levels were determined by high-performance liquid chromatography. Histological and immunohistochemical (Ki67, activated caspase-3) analysis of tumors were performed. The effect of ASA on tumor prostaglandin E2 (PGE2) levels was also evaluated. In vitro cell proliferation and migration were significantly inhibited while apoptosis increased (p<0.05) by ASA. Although ASA did not induce tumor remission, tumor progression was significantly lower in ASA-treated mice when compared to non-treated animals (478% in mice treated with 5mg/kg/day ASA vs. 2696% control; 748% in mice treated with 50mg/kg/day ASA vs. 2670% control). Maximum tumor inhibition was 92 and 85%, respectively. This effect was associated with a significant decrease of proliferation index in tumors. ASA 5mg/kg/day did not modify tumor PGE2 levels. Whereas tumor PGE2 content in mice treated with ASA 50mg/kg was lower than in control mice, the difference was not significant. Although these results need to be confirmed in other EAC cells, our data suggest a role for ASA in the treatment of this tumor.

Do we need antiplatelet therapy in thrombocytosis? Pro

SummaryThrombocytosis (defined as platelets &gt;450 × 109/l) has several aetiologies. After having excluded spurious thrombocytosis (e. g., due to microspherocytes, schistocytes, cryoglobulins, or bacteria), the differential diagnosis of true thrombocytosis encompasses secondary causes (as diverse as inflammation, infection, malignancy, iron deficiency, or asplenia), primary hereditary (rare forms of familial thrombocytosis) and primary acquired entities (either in the context of a myelodys-plastic syndrome or more frequently a myeloproliferative neoplasia). This manuscript addresses the following aspects: 1) diagnostic approach to thrombocytosis; 2) various mechanisms leading to a high platelet count; 3) potential of some of these mechanisms to modulate platelet function, producing hyper-reactive platelets and thus exerting a direct impact on the thrombotic risk; 4) indication of anti-thrombotic treatment in patients with thrombocytosis. There is a single prospective randomized clinical trial showing the benefit of acetyl-salicylic acid in polycythaemia vera. For other types of primary thrombocytosis and for secondary forms, treatment decisions have to be individualized according to the patient thrombotic and bleeding risks, taking into account the mechanism causing thrombocytosis. This manuscript discusses experimental and clinical data suggesting that besides patients with essential thrombocythaemia and other forms of primary thrombocytosis also those with thrombocytosis in the context of chronic inflammation, malignancy, or exposure to high altitude might benefit from anti-platelet treatment.

Effects of low-dose acetylsalicylic acid and atherosclerotic vascular diseases on the outcome in patients with severe sepsis or septic shock

Sepsis and its sequelae of multiple organ failure is one of the leading causes of death in the industrial countries. Several studies have shown that patients who are treated with low-dose acetyl salicylic acid (ASA) for secondary prevention of atherothrombosis may have a lower risk to develop organ failure in the case of critical illness. The benefit of ASA is probably due to an inhibition of platelet activation as well as an increase in the formation of anti-inflammatory lipoxin A4. On the other hand, the effect of ASA could be – at least partially – an indirect one, caused by atherosclerotic vascular diseases as the cause of ASA treatment. Atherosclerosis is considered as a moderate systemic inflammation and we hypothesise that this chronic condition could have an impact on the outcome in sepsis. To get more information on the benefit of ASA in critically ill patients and on possible interference with atherosclerotic vascular diseases, we analysed the medical records of 886 septic patients who were admitted to the surgical intensive care unit (ICU) of a university hospital. Logistic regression analysis indicated that patients who were treated during the ICU stay with ASA (100 mg/d) had a significantly lower mortality. Odds ratios (ORs; with 95% confidential intervals) of 0.56 (0.37–0.84) and 0.57 (0.39–0.83) were calculated for ICU and hospital mortality, respectively. In contrast, statin treatment did not have significant effect on mortality. Diagnosis of atherosclerotic vascular diseases according to ICD classification did not influence ICU mortality but lowered hospital mortality (OR = 0.71 (0.52–0.99)). Subgroup analysis provided preliminary evidence that clopidogrel when given as only anti-platelet drug may have a similar benefit as ASA, but the combination of ASA and clopidogrel failed to improve the outcome. The time course of plasma fibrinogen and procalcitonin levels indicate that ASA seems to reduce the activation of haemostasis and increase the resolution of inflammation. It is concluded that prospective interventional studies should be done to test the use of ASA as novel therapeutic approach in critically ill patients.

Prevención primaria con aspirina

The benefit of acetylsalicylic acid and other antiplatelet drugs in secondary prevention is well established, however it use in primary prevention continues to be controversial. On the one hand, the benefit obtained is very near the potential damage arising from its use (mainly gastrointestinal bleeding), and on the other, the net benefit is less, given that its aim is to prevent the occurrence of vascular events in situations with a lower baseline risk.Antiplatelet treatment with aspirin in primary prevention has been evaluated in clinical trials and several meta-analyses, comparing its efficacy with a placebo, and with results noted for their heterogeneity.The mechanisms of action of different antiplatelet drugs, as well as the existing evidence with aspirin in primary prevention, the directions for its use by different Scientific Societies, and the cost/benefit of the intervention are reviewed.

¿Antiagregamos adecuadamente a los pacientes diabéticos tipo 2?

ObjectiveTo estimate how many type 2 diabetic patients receive antiplatelet therapy according to the American Diabetes Association (ADA) guidelines on primary and secondary prevention. DesignA descriptive, cross-sectional study based on information in medical records. A random sample of 170 type 2 diabetics seen in an urban Health Centre was studied. MeasurementsThe data collected including, age, sex, antiplatelet therapy according to the ADA, antiplatelet therapy indicated, cardiovascular risk factors, cardiovascular disease, and other clinical parameters. ResultsOf the subjects analysed, 56.9% were males, and the mean age was 67.8 years. The majority of patients (71.2%) were on primary prevention, and 44.4% of the diabetics were receiving adequate antiplatelet therapy according to the ADA. Among the subjects on secondary prevention, 90.9% received adequate antiplatelet therapy, while only 25.7% of those on primary prevention received it, which was significant. The most used antiplatelet drug was acetylsalicylic acid (ASA). ConclusionsA large proportion of diabetes on primary prevention does not receive adequate antiplatelet therapy, according to the ADA. However, patients on secondary prevention receive sufficient antiplatelet treatment. The benefits of ASA in reducing cardiovascular disease are well documented in patients with cardiovascular disease. On the other hand, the role of antiplatelet therapy in diabetics on primary prevention is not clear and is the subject of discussion. From 2006 to 2011, the ADA has modified the recommendation level of primary prevention antiplatelet therapy, thus decreasing the percentage of patients that may be given antiplatelet therapy with ASA, to the extent that it increases the cardiovascular risk calculation required for its indication.

Hypertension in diabetes: A call to action

The Canadian Hypertension Education Program, Blood Pressure Canada, Canadian Hypertension Society, Heart and Stroke Foundation of Canada, Canadian Diabetes Association, College of Family Physicians of Canada, Canadian Pharmacists Association and the Canadian Council of Cardiovascular Nurses call on Canadian health care professionals to redouble efforts to help patients achieve treatment targets (blood pressure less than 130 mmHg systolic and less than 80 mmHg diastolic) in people with diabetes. Treatment of high blood pressure in people with diabetes results in large reductions in death and disability within a short period of time and needs to be a therapeutic priority. Achieving blood pressure targets requires sustained lifestyle modification, and three or more drugs including a diuretic are often required. Antihypertensive treatment in people with diabetes is one of the few medical treatments estimated to reduce overall health costs. The cost of treatment is less than the cost of complications prevented. Blood pressure needs to be assessed at all visits and home blood pressure assessment is encouraged. Management strategies need to include assessment and management of cardiovascular risks including smoking, unhealthy eating, physical inactivity, abdominal obesity, dyslipidemia as well as dysglycemia. The risks and benefits of acetylsalicylic acid in primary prevention of cardiovascular disease are uncertain in people with hypertension and diabetes. Intensive individualized lifestyle modification is recommended to prevent and treat hypertension, dyslipidemia, dysglycemia and other vascular risks in people with diabetes.

Questions non résolues concernant la stratification du risque et la prise en charge des patients atteints de maladie coronarienne subissant une chirurgie vasculaire majeure

The purpose of this article, with a specific focus on patients undergoing vascular surgery, is to review controversial issues related to mechanisms of perioperative myocardial infarction (MI), coronary artery disease detection, and strategies to reduce perioperative complications. We propose explanations for the many conflicting results that have recently emerged in the literature.Source documents: We searched MEDLINE and reviewed all relevant manuscripts and scientific statements regarding management of patients undergoing non-cardiac surgery.Identification and prevention of ischemia in patients undergoing vascular surgery remains controversial. While the identification of preoperative ischemia is a marker of a higher perioperative risk, the value of identifying such ischemia has been questioned. We believe this may be, at least in part, due to our limited understanding of perioperative MI. Appropriate management of patients, based on the results of such testing, is likely the key to improving outcomes, and deserves further investigation. Efforts aimed at reducing the ischemic consequences of severe coronary plaques (by revascularization or beta-blocker therapy) have yielded conflicting results. The use of high doses of preoperative beta-blocker therapy may be harmful. Some studies suggest a promising role for statin therapy. Benefits of acetylsalicylic acid must be weighted against the risk of bleeding.Many questions remain unanswered about the impact of detecting inducible ischemia, and the role of revascularization or beta-blockers in patients undergoing vascular surgery. A better understanding of the pathophysiology of perioperative MI is critical, in order to identify the best approach to improve cardiac outcomes in these patients.

Does One Pill a Day Keep the Colonoscopist Away?

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