Análise do perfil hemostático e do risco tromboembólico em cães submetidos ao tratamento com prednisona

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ultra-estrutura e função plaquetária em indivíduos normais e pacientes com aterosclerose obliterante periférica

Pós-graduação em Patologia - FMB

Influência das alterações físicas e químicas sobre a função plaquetária e a expressão da GPIIbIIa em concentrados de plaquetas caninos estocados

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudos estruturais experimentais e teóricos com proteínas do veneno da serpente Bothrops jararacussu

Pós-graduação em Ciências Biológicas (Genética) - IBB

Planejamento, síntese e avaliação farmacológica de novos compostos 1,2,5-oxadiazol-2-n-óxido úteis como preventivos de aterotrombose

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hemostatic profile and thromboembolic risk in healthy dogs treated with prednisone: a randomized controlled trial

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Crystallization and preliminary X-ray diffraction studies of an L-amino-acid oxidase from Lachesis muta venom

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antiplatelet drugs reduce the immunoinflammatory response in a rat model of periodontal disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Aplicação de testes hemostáticos na avaliação do risco trombótico em cadelas com carcinoma mamário

Pós-graduação em Medicina Veterinária - FMVZ

Síntese, caracterização e avaliação farmacológica de derivados N-acilhidrazônicos para a prevenção de aterotrombose

Atherosclerosis is a chronic inflammatory disease characterized by accumulation of lipid and fibrous components in arterial vessels, giving rise to atheromas. Development of Atheromatou plaques leads to arterial steatosis, triggering ischemic events. Atherotrombosis has a strong correlation with atherosclerosis, where rupture of atheromatous plaques cause release of vessel wall's pro-thrombotic components, activating platelet aggregation and thromosis. Due to the major role played by platelets on thrombus-embolic conditions, drugs that inhibit platelet aggregation demonstrate great relevance for atherothrombosis prevention, reducing patient mortality. Currently, there are a variety of drugs acting on several different targets, preventing platelet activation. However, these therapies demosntrate side effects such as thrombocytopenia, neutropenia, hemorrhage and low oral availability. Thus, the application of molecular modifications such as hybridization can produce novel, more efficient antiplatelet aggregation inhibitors. In this project we describe the synthesis and characterization of novel N-acilhydrazone compounds, acting through multiple mechanisms such as platelet calcium chelation and nitric oxide donation by furoxanic subunits. Furthermore, we demonstrate that such compounds exhibit biological activity in in vivo bleeding time, in vitro antiplatelet aggregation and in vivo antinociceptive assays. Therefore, novel N-acilhydrazone compounds demonstrate potential as antiplatelet drugs for atherothrombosis prevention.

Participação do óxido nítrico na fisiopatologia da doença renal crônica

Nitric oxide (NO) is a free radical gas, inorganic, which has seven electrons of nitrogen and oxygen eight, possessing an unpaired electron. This radical is produced from L-arginine by a reaction mediated by the enzyme NO synthase. NO it is about a radical of who acts abundant on a variety of biological processes, particularly when produced by endothelial cells plays a significant role in cardiovascular control, as a modulator of peripheral vascular resistance and platelet aggregation. This free radical has also a neurotransmitter and mediator of the immune system. NO kidney function has been considered in many physiological functions such as: (a) regulation of hemodynamics and glomerular function tubuloglomerular, (b) participation in pressure natriuresis (c) maintaining medullar perfusion (d) inhibiting sodium reabsorption tubular, and (e) acting as a modulator of the activity of the sympathetic nervous system. Given these functions, the occurrence of its deficiency is associated with chronic kidney disease (CKD) in vasoconstriction and consequently glomerular hypertension, high blood pressure (HBP), proteinuria and progression of renal dysfunction. This work has the scope to describe the role of NO in renal physiology and pathophysiology of CKD.

Avaliação das alterações hemorrágicas e tromboembólicas em cães com doença renal crônica

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hemocompatibility of poly(epsilon-caprolactone) lipid-core nanocapsules stabilized with polysorbate 80-lecithin and uncoated or coated with chitosan

The hemocompatibility of nanoparticles is of critical importance for their systemic administration as drug delivery systems. Formulations of lipid-core nanocapsules, stabilized with polysorbate 80-lecithin and uncoated or coated with chitosan (LNC and LNC-CS), were prepared and characterized by laser diffraction (D[4,3]: 129 and 134 nm), dynamic light scattering (119 nm and 133 nm), nanoparticle tracking (D50: 124 and 139 nm) and particle mobility (zeta potential: -15.1 mV and + 9.3 mV) analysis. In vitro hemocompatibility studies were carried out with mixtures of nanocapsule suspensions in human blood at 2% and 10% (v/v). The prothrombin time showed no significant change independently of the nanocapsule surface potential or its concentration in plasma. Regarding the activated partial thromboplastin time, both suspensions at 2% (v/v) in plasma did not influence the clotting time. Even though suspensions at 10% (v/v) in plasma decreased the clotting times (p < 0.05), the values were within the normal range. The ability of plasma to activate the coagulation system was maintained after the addition of the formulations. Suspensions at 2% (v/v) in blood showed no significant hemolysis or platelet aggregation. In conclusion, the lipid-core nanocapsules uncoated or coated with chitosan are hemocompatible representing a potential innovative nanotechnological formulation for intravenous administration. (C) 2012 Elsevier B. V. All rights reserved.

Thrombin-Receptor Antagonist Vorapaxar in Acute Coronary Syndromes

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.)