748 resultados para Aspirin-Mimics
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Introduction & Objectives: Thrombosis of the renal allograft is expected to occur in 1–6% of kidney transplants, and graft loss is expected in almost all cases. Anticoagulant and anti-platelet agents could serve as an adjunctive preventive measure, but sound evidence of benefits are still lacking, in this setting. We therefore assessed the efficacy and safety of anticoagulant and anti-platelet agents, in reducing the rate of renal allograft thrombosis. Methods: A review of the literature was carried out in major databases (MEDLINE, EMBASE and LILACS), with a comprehensive search strategy, to locate all available case series studies of anticoagulant and/or anti-platelet prophylaxis of thrombosis in renal transplantation. The date of the last search was 11 August 2014. We pooled all case series in a proportional meta-analysis. Statistical significance was achieved if the 95% confidence intervals obtained for each intervention did not overlap. Results: Our search strategy retrieved 7160 titles, from which 21 case series were chosen for analysis. A total of 3246 patients were identified (1718 treated with antiplatelet and/or anticoagulant agents, and 1528 non-treated control subjects). Allograft thrombosis occurred in 7.24% (95% CI 3.45 to 12.27%) of the patients receiving no intervention, compared to 3.38% (95% CI 1.45 to 6.1%), 1.2% (95% CI 0.6 to 2.1%) and 0.47% (95% CI 0.001 to 1.79%), in the anticoagulant, aspirin, and aspirin + anticoagulant groups, respectively. Bleeding complication rates were 28.0% (95% CI 15.4 to 42.7%) for anticoagulants, compared to 12.13% (95% CI 0.8 to 33.93%) for aspirin + anticoagulant, 0.31% (95% CI 0.0001 to 1.32%) for aspirin, and 6.1% (95% CI 2.2 to 11.7%) for the control group. Conclusions: Aspirin is more effective in reducing allograft thrombosis, after kidney transplantation, whether alone or in association with an anticoagulant, when compared to no drug prophylaxis, and without higher haemorrhagic complication rates. Anticoagulants, when used alone, do not show a beneficial effect on thrombosis rates, additionally yielding higher bleeding rates.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Bone formation is dependent on the differentiation of osteoblasts from mesenchymal stem cells (MSCs). In addition to serving as progenitors, MSCs reduce inflammation and produce factors that stimulate tissue formation. Upon injury, MSCs migrate to the periodontium, where they contribute to regeneration. We examined the effect of clopidogrel and aspirin on MSCs following induction of periodontitis in rats by placement of ligatures. We showed that after the removal of ligatures, which induces resolution of periodontal inflammation, clopidogrel had a significant effect on reducing the inflammatory infiltrate. It also increased the number of osteoblasts and MSCs. Mechanistically, the latter was linked to increased proliferation of MSCs in vivo and in vitro. When given prior to inducing periodontitis, clopidogrel had little effect on MSC or osteoblasts numbers. Applying aspirin before or after induction of periodontitis did not have a significant effect on the parameters measured. These results suggest that clopidogrel may have a positive effect on MSCs in conditions where a reparative process has been initiated.
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The bone repair process is controlled by complex molecular mechanisms that involve systemic and local factors. Fibrin glue is derived from human plasma and mimics the final pathway of coagulation network. Tranexamic acid inhibits fibrinolysis and prevents or decreases the formation of degradation products of fibrin and fibrinogen. The purpose of this study was to evaluate histologically in rats the effect of tranexamic acid associated with the fibrin glue on bone healing. The experiment used 60 (n = 5) male rats in: GI: Control, GII: fibrin glue, GIII tranexamic acid and GIV /fibrin glue/tranexamic acid. Bone defect (2.5mm diameter) was created in right tibia. The animals were euthanized at 7,14 and 30 days postoperatively, and the pieces were processed with hematoxylin and eosin. The results showed at 7 days post-operative surgical cavity filled with dense connective tissue rich in fibroblasts, permeated by delicate neoformed bone trabeculae in percentage of 70-80% for GI, GII and GIII and GIV to 94.8%. At 14 days post-operative newly formed bone was found between 75-85% for GI, GII and GIII and percentage above 95% for GIV. At 30 days postoperative GI and GIV showed 95-100% of mature bone tissue; GII and GIII in percentage close to 80-90%. Based on the results and methodology is concluded that fibrin / tranexamic acid glue association has positive action on bone repair.
Efeito do treinamento físico aeróbio na reatividade vascular da artéria ilíaca em camundongos LDL-/-
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Pós-graduação em Odontologia - FOAR
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Maximum-likelihood decoding is often the optimal decoding rule one can use, but it is very costly to implement in a general setting. Much effort has therefore been dedicated to find efficient decoding algorithms that either achieve or approximate the error-correcting performance of the maximum-likelihood decoder. This dissertation examines two approaches to this problem. In 2003 Feldman and his collaborators defined the linear programming decoder, which operates by solving a linear programming relaxation of the maximum-likelihood decoding problem. As with many modern decoding algorithms, is possible for the linear programming decoder to output vectors that do not correspond to codewords; such vectors are known as pseudocodewords. In this work, we completely classify the set of linear programming pseudocodewords for the family of cycle codes. For the case of the binary symmetric channel, another approximation of maximum-likelihood decoding was introduced by Omura in 1972. This decoder employs an iterative algorithm whose behavior closely mimics that of the simplex algorithm. We generalize Omura's decoder to operate on any binary-input memoryless channel, thus obtaining a soft-decision decoding algorithm. Further, we prove that the probability of the generalized algorithm returning the maximum-likelihood codeword approaches 1 as the number of iterations goes to infinity.
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In this paper we use a coupled ocean-atmosphere model to investigate the impact of the interruption of Agulhas leakage of Indian ocean water on the tropical Atlantic, a region where strong coupled ocean-atmosphere interactions occur. The effect of a shut down of leakage of Indian ocean water is isolated from the effect of a collapse of the MOC. In our experiments, the ocean model is forced with boundary conditions in the southeastern corner of the domain that correspond to no interocean exchange of Indian ocean water into the Atlantic. The southern boundary condition is taken from the Levitus data and ensures an MOC in the Atlantic. Within this configuration, instead of warm and salty Indian ocean water temperature (cold) and salinity (fresh) anomalies of southern ocean origin propagate into the South Atlantic and eventually reach the equatorial region, mainly in the thermocline. This set up mimics the closure of the ""warm water path"" in favor of the ""cold water path"". As part of the atmospheric response, there is a northward shift of the intertropical convergence zone (ITCZ). The changes in trade winds lead to reduced Ekman pumping in the equatorial region. This leads to a freshening and warming of the surface waters along the equator. Especially in the Cold Tongue region, the cold and fresh subsurface anomalies do not reach the surface due to the reduced upwelling. The anomaly signals are transported by the equatorial undercurrent and spread away from the equator within the thermocline. Part of the anomaly eventually reaches the Tropical North Atlantic, where it affects the Guinea Dome. Surprisingly, the main effect at the surface is small on the equator and relatively large at the Guinea Dome. In the atmosphere, the northward shift of the ITCZ is associated with a band of negative precipitation anomalies and higher salinities over the Tropical South Atlantic. An important implication of these results is that the modified water characteristics due to a shut down of the Agulhas leakage remain largely unaffected when crossing the equatorial Atlantic and therefore can affect the deepwater formation in the North Atlantic. This supports the hypothesis that the Agulhas leakage is an important source region for climate change and decadal variability of the Atlantic.
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Objective: The aim of this study is to investigate the effects of pregabalin on the behavior of rats under the influence of ketamine, an NMDA receptor antagonist that mimics the symptoms of schizophrenia. Methods: Rats were injected with saline or 25 mg/kg ketamine intraperitoneally. After that, behavior modifications were investigated by the evaluation of stereotypy and hyperlocomotion, after treating rats with pregabalin (at doses of 30 mg/kg or 100 mg/kg) or placebo (saline solution). Results: The administration of pregabalin reduced ketamine-induced hyperlocomotion. However, neither doses of pregabalin had a significant effect on ketamine-induced stereotypy. Conclusion: This is the first study to investigate the effects of pregabalin using an animal model of psychosis. Furthermore, our results indicate that behavioral changes induced by ketamine in rats can be reversed with the use of pregabalin, suggesting its potential to treat psychotic symptoms.
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BACKGROUND Vorapaxar is a new oral protease-activated receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. METHODS In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5010 vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. CONCLUSIONS In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.)
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Background The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated. Methods In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel. Results At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P = 0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P = 0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group. Conclusions Among patients with unstable angina or myocardial infarction without ST- segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.)