Thromboelastography (TEG), a viscoelastic test for blood coagulation, has been suc- cessfully applied for hemostatic therapy, transfusions, perioperative care, and he- mophilia due to its point-of-care analysis and timely results [9, 10]. Moreover, TEG rapidly measures formation and dynamics of coagulation in blood. TEG has attract- ed increasing amounts of attention for its value in the treatment of ischemic heart and cerebrovascular diseases. Concerning aspirin resistance in CAD, we hypothesized that TEG might contribute to preventing recurrence of thrombosis due to the fact that patient platelet function is able to be monitored by TEG and antiplatelet therapy could be adjusted in time.
Summary: Introduction: The issue of resistance to antiplatelet therapy has raised many questions in the area of neurovascular diseases. The first objective of this work was to determine the prevalence of aspirin resistance in neurovascular patients with clinical non-responsiveness to aspirin treatment and a high-risk of atherothrombotic complications using two interpret- able and independent methods (aggregation and PFA 100). The second objective was to find the correlation between both assays and to evaluate the results in groups at risk for various cerebrovascular diseases. Material and methods: Laboratory tests of aspirin resistance were performed in 79 patients with clinical non-responsiveness to aspirin treatment suffering from neurovascular diseases. Patients were divided into the two groups: expected low risk for aspirin resistance due to the first manifestation of a neurovascular disease (n = 34) and expected high risk due to the second clinical manifestation of a neurovascular disease (n = 45). Results: The prevalence of aspirin resistance in both groups combined as determined by the PFA-100 and CPG techniques were 50.6% and 17.7%, respectively. No correlation was found between the two techniques. Conclusions: No significant prevalence of aspirin resistance was demonstrated by either method despite the heterogeneous pathophysiological mechanisms. However, we are presently unable to provide an accurate opinion on the value of laboratory test result or routine monitoring in clinical neurology.
Aspirin became a cornerstone in the treatment of coronary artery disease and widely used in the secondary prevention of vascular events. Aspirin resistance remains a poorly defined term though clinical definition is failure of the drug to prevent an atherothrombotic event despite the regular intake of appropriate doses is a relatively common problem. Various laboratory parameters assessing its efficacy, like bleeding time, platelet reactivity, thromboxane A2 (TXA2) production and measurement of platelet aggregation have confirmed the lack of its uniform effect on the platelets. Various molecular mechanism responsible for Aspirin resistance include Insufficient suppression of COX-1, over- expression of COX-2 mRNA, Erythrocyte induced platelet activation, Genetic polymorphism of enzymes like COX-1, COX-2 or thromboxane A2 synthase. Clinical factor like non compliance of patient is also responsible for Aspirin resistance. The limitations in understanding Aspirin resistance include difficulties in assessing platelet function and aspirin resistance and contributed to variable reporting of Aspirin resistance. Therefore, the definition of Aspirin resistance requires refinement to include genetic polymorphism of various enzymes responsible for Aspirin resistance. However, various techniques for platelet analysis also require modification to understand Aspirin resistance.
Methods: This was a cross-sectional, interventional study, which was implemented from October to November 2012 at the Hospital Universiti Sains Malaysia (HUSM). Sixty-nine patients with diabetes who were taking aspirin were enrolled. The glycosylated haemoglobin (HbA1c) and C-reactive protein (CRP) levels were measured in these patients. The thromboelastography (TEG) level was measured using a TEG machine by a trained technician employing standard methods. The variables obtained were analysed for prevalence of aspirin resistance, HbA1c, CRP, and TEG level. The Chi-square test (and Fisher exact test where applicable) were used to evaluate the associations between aspirin resistance with glycaemic control (HbA1c) and inflammatory markers (CRP).
tion: a problem termed “aspirin resistance”. Aspirin re- sistance (AR), defined as failure of suppression of thromboxane generation, increases the risk of cardiovas- cular events in a high-risk population . Causes of as- pirin resistance include concurrent use of nonsteroidal anti-inflammatory drugs, such as ibuprofen that may compete with aspirin at the COX-1 receptor site , po- lymorphisms in the COX-1 gene , poor glucose con- trol, body weight and conditions associated with a high platelet turnover [7-10]. Objective of our study was to evaluate the prevalence of AR among subjects with moderate control and its association with inflammatory markers and cytokines.
Andersen et al.  showed that the levels of TXA 2 were extremely low in both aspirin responders and non- responders. However, the levels of soluble P-selectin were significantly higher in non-responders than responders. Resistance to other antiplatelet drugs has also been described. "Clopidogrel resistance" has been documented . Clopidogrel non-responders were defined by an inhibition of ADP [5 and 20 mol/L] induced platelet aggregation that was less than 10% of the baseline value 4 h after clopidogrel 600 mg intake. Semi-responders corre- sponded to patients with an inhibition of 10 to 29%; responders are patients with an inhibition over 30%. Up to 4.7% of the patients undergoing coronary stenting developed thrombotic stent occlusion, despite intensive clopidogrel treatment; the parallel with aspirin resistance seems striking. However, as there is no standard defini- tion of aspirin resistance, comparison between the results of different studies is difficult.
introduced. In the PubMed browsing this term resulted in over 2000 publications. True aspirin resistance is the inabil- ity of aspirin to acetylate Ser259 residue in platelet COX1. The ineffectiveness of aspirin in protecting an individual from acute vascular events is often considered “aspirin resistance” although such cases are very likely related to the fact that aspirin inhibits effectively and selectively only one out of several pathways leading to platelet activation [9, 10]. It fails to inhibit platelet activation induced by strong agonists, like thrombin or high dose of collagen and only partially inhibits ADP induced platelet aggregation. The involvement of such stimuli in platelet activation could be prevalent in atherosclerotic vessel. In many studies non- compliance was not adequately controlled and was not separated from aspirin resistance. Further problem was the lack of laboratory tests that specifically detect the acetyla- tion of COX1. Non-responsiveness to aspirin as measured by laboratory tests non-specific for detecting the effect of aspirin was also confused with aspirin resistance. In a recent study we developed monoclonal antibodies react- ing with acetylated and non-acetylated COX1 (acCOX1 and nacCOX1, respectively) for the first time, and utiliz- ing these antibodies a highly specific and sensitive method that detects 2.5 % of platelet nacCOX1 was developed . Using this method that measures COX1 acetylation by aspirin directly, no aspirin resistance was found among 108 healthy volunteers taking 100 mg enteric-coated aspi- rin daily for 7 days. The same results were obtained by COX1-dependent functional tests, like AA-induced TXB 2
Background: The effect of genetic variants on aspirin resistance (AR) remains controversial. We sought to assess the association of genetic variants with AR and early clinical outcomes in patients with acute ischemic stroke (IS). Methods: A total of 850 acute IS patients were consecutively enrolled. Platelet aggregation was measured before and after a 7 – 10 day aspirin treatment. The sequences of 14 variants of COX-1, COX-2 , GPIb, GPIIIa, P2Y1 and P2Y12 were determined using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR). The primary outcome was early neurological deterioration (END) within 10 days of admission. The secondary outcome was a composite of early recurrent ischemic stroke (ERIS), myocardial infarction (MI) and death within 10 days of admission.
Aspirin may prolong bleeding slightly not more than 1.2 - 2 times of pre-aspirin bleeding time. After discontinuation the bleeding time will become normal on fourth day and platelet aggregatory tests will become normal on eighth day. Aspirin must be stopped at least 1 week before surgery in surgical patients. Aspirin is rapidly converted into salicylic acid in the body.
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A significant proportion of patients at risk for throm- botic episodes fail to achieve an adequate control of platelet aggregability when placed on aspirin therapy. These individuals are at greatly increased risk for cardio- vascular events—in large part because of the metabolic factors that destabilise their platelets—but clinical studies demonstrate some ancillary measures that promote greater platelet stability can notably decrease their risk. Nutraceutical measures, because of their relative safety, affordability and broader protective metabolic impacts, may have particular merit for this purpose.
A special group to be considered are patients with dual antiplatelet resistance as these patients bear the greatest risk of major adverse events, such as stent thrombosis. In accordance with previous studies we identified a pre- valence of 8.5% to be dual low responders. An analysis of the RECLOSE trial cohort showed a prevalence of 6% with dual resistance to ASA and clopidogrel . This dual non-responsiveness was an independent risk factor and led to markedly higher rates of DES thrombosis (11.1%) as compared to isolated ASA (2.3%) or clopido- grel non-responsiveness (2.2%) . Other data revealed a prevalence of 10.4% dual low response and suggest a high cardiovascular risk after PCI for these patients with the need for intensified antiplatelet therapy and follow- up . As a consequence not only CLR should be identified to determine the patients’ risk, but ALR is relevant to the clinical outcome as well.
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evaluate if ADP levels could be of importance in the iden- tification of patients with increased risk of myocardial inf- arction in the future. Why did the patients with aspirin resistance have higher ADP levels? It is possible that this was the result of a more pronounced cardiac ischemia. However, ADP levels did not correlate with either CKMB or troponin T levels. Another explanation could be that subgroups of patients are more dependent on the ADP positive feedback system than on the thromboxane sys- tem, and therefore more aspirin resistant. Then our find- ing of increased ADP levels may reflect an increased ADP release from platelets. These patents may benefit more from inhibitors of ADP mediated platelet activation than aspirin.
Background: Prognostic factors are associated with the risk of future health outcomes in individuals with a particular health condition. The prognostic ability of such factors is increasingly being assessed in both primary research and systematic reviews. Systematic review methodology in this area is continuing to evolve, reflected in variable approaches to key methodological aspects. The aim of this article was to (i) explore and compare the methodology of systematic reviews of prognostic factors undertaken for the same clinical question, (ii) to discuss implications for review findings, and (iii) to present recommendations on what might be considered to be ‘ good practice ’ approaches. Methods: The sample was comprised of eight systematic reviews addressing the same clinical question, namely whether ‘ aspirin resistance ’ (a potential prognostic factor) has prognostic utility relative to future vascular events in patients on aspirin therapy for secondary prevention. A detailed comparison of methods around study identification, study selection, quality assessment, approaches to analysis, and reporting of findings was undertaken and the implications discussed. These were summarised into key considerations that may be transferable to future systematic reviews of prognostic factors.
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This is the first study of clopidogrel and aspirin resistance among patients undergoing cerebrovascular stent placement and suggests that point-of-care aggregometry is feasible. Two prior small studies addressed aggregometry testing for abcix- imab during cerebrovascular stent placement. 8,9 In coronary literature, there have been many reports of clopidogrel and aspirin resistance, with the finding that high poststent platelet reactivity may be a predictor of recurrent coronary events and stent thrombosis. 6,10-13 In our study, we were unable to corre- late percentage platelet inhibition to stent thrombosis, re-ste- nosis, or any clinical outcome. However, because follow-up management was not standardized, subsequent dosage and duration of antiplatelet drug therapy may have been influ- enced by aggregometry results at the time of stent placement. Although we found no relationship between the dose or timing of clopidogrel administration and platelet inhibition, others have recently shown that higher dose clopidogrel load- ing (600 mg) can produce greater platelet inhibition in coro- nary patients. 14-16 Differences in the studies may explain this
To further confirm these data, we xenotransplanted PANC-1 cells orthotopically to the pancreas of immunodeficient mice followed by treatment with aspirin or gemcitabine. Aspirin was used in a dose of 200 mg/kg, according to a publication, in which the same concentration was successfully used for the treatment of mice with orthotopically growing PANC-1 xenografts . The administration of aspirin or gemcitabine alone decreased tumor growth, but the combination of both agents significantly inhibited tumor formation (Figure 6A). These results are reflected by the survival time of mice of each group, which was significantly longer in the combination group (Figure 6B). Also, there was a significant longer survival of gemcitabine-treated mice upon co-treatment with aspirin. No macroscopic metastases were detected in the livers and lungs, but we observed two mice in the control group and one mouse in the gemcitabine group with celiac implantation metastasis, while no metastases were detected in the aspirin and combination groups (data not shown). While aspirin had no obvious side effects, as evident from measures of body weight, plasma creatinine and urea nitrogen, gemcitabine alone or combined with aspirin significantly reduced the body weight and increased the plasma creatinine levels (Figure 6C, 6D). In contrast, liver necrosis was not induced by any treatment (Figure S5). Immunohistochemical staining of xenograft tissue from treated mice revealed a reduction in SOX2, CD133, p65 and TNF-α, as well as the ECM components fibronectin and collagen, and more pronounced effects were observed following combination treatment (Figure 6E).
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thromboxane B2 (Tx-M) were measured in urine by mass spectrometry during continuing administration of aspirin. To define the relationship of aspirin intake to endogenous prostacyclin biosynthesis, sequential urines were initially collected in individuals prior to, during, and subsequent to administration of aspirin. Despite inter- and intra-individual variations, PGI-M excretion was significantly reduced by aspirin. However, full mass
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on collagen (5 mg/ml)-induced aggregation to see if they con- tributed to the inhibitory actions of 1, which might explain its greater potency than aspirin. Isosorbide, salicylic acid, isosorbide-2,5-disalicylate and isosorbide-5-salicylate (see Figure 1b) were incubated in PRP in the concentration range 10–300 mm before triggering aggregation. None of the hydrolysis products significantly inhibited aggregation induced by collagen (5 mg/ml) (n = 3 at 11 concentration levels). The compounds were also co-incubated in the pres- ence of aspirin to see if they potentiated its actions (either pharmacologically or by affecting disposition). None of the compounds affected aspirin’s activity apart from isosorbide- disalicylate, which trended non-significantly towards an attenuation of aspirin’s inhibitory effect (maximally 10%) when co-incubated in the range 50–500 mm.
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Our finding of reduced all-cause mortality in the A + D group at 12months follow-up is somewhat puzzling. Previ- ously two large, randomised, studies [8,9] have shown A + D to be effective for secondary stroke prevention, but all- cause mortality was not reduced. Furthermore, in TIA patients The American-Canadian Co-Operative Study Group (21) has demonstrated that after a mean follow-up of 25 months there was no difference in mortality, stroke or retinal infarction between patients randomised to aspirin plus placebo or aspirin plus dipyridamole. There are several explanations for this discrepancy between our results and previous data. One explanation could be that the present study was non-randomised in contrast to pre- vious randomised trials, which means that our results must be interpreted with extreme caution. In previous studies [8,9,21] the mean follow-up was between 24 months and 3.5 years in comparison with 12-months follow-up in the present study. During longer follow-up, risk factors for car- diovascular mortality may be more impending and may counteract the early positive effects of A + D.
ABSTRACT Safe drinking water is the need of human as well as plants and animals. The emerging technology, emerging processes and emerging products have also given birth to emerging pollutants. A number of emerging as well as priority pollutants have been listed across the globe. Every year new pollutants are added to the priority pollutants list. The focus of the nations and environmental agencies across the world is now shifting to safer environment. Only safer environments can guarantee longetivity to the planet. Pharmaceuticals and pharmaceutical pollutants have also been listed as priority pollutants. Though the concentration may be less in some cases still their removal from water is a priority due to harmful effects these pollutants cause on the human health. Some contaminants cannot be removed by the conventional treatment methods hence special treatment has to be done. There are different Advance Oxidation Processes. Ultrasound is one such advance oxidation process which offers several benefits over the conventional oxidation processes. The degradation of drug Aspirin was studied using ultrasound. Aspirin is a listed priority pollutant. The occurrence of Aspirin has also been reported. Though Aspirin maybe beneficial to human health still excess quantity cannot be tolerated by human health and there are side effects of excess quantity. Comparative degradation under natural and induced conditions was studied employing a probe system under different conditions. Under all the induced conditions of study the drug showed good degradation response. The process can be one possible option for reducing priority pollutants from water.
There is increasing concern that aspirin is linked to cerebral haem- orrhages that may be primary or secondary. Again these are pre- dicted by its known actions on platelets and small blood vessels. It is well known that aspirin can cause gastric haemorrhages, prob- ably via its anti-prostaglandin actions, and that these can be fatal. As aspirin has a range of pharmacological effects it is possible that it will be found to influence the progress of different dementias in different ways, either beneficially or adversely.
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