Purpose. The use of antiplatelet agents in patients hospitalized with ischemic stroke was studied. Methods. Patients with a primary or secondary diagnosis of noncardiogenic, thrombotic ischemic stroke from January 2002 through December 2004 were included in the analysis. Patients were then subdivided into four treatment groups and one no-treatment group based on whether they were charged for any of four antiplatelet regimens (low-dose aspirin [≤325 mg daily], extended-release dipyridamole 200 mg with aspirin 25 mg, clopidogrel 75 mg, and clopidogrel 75 mg [as the bisulfate] plus low-dose aspirin) at any time during hospitalization. Patients who did not receive any of these medications during hospitalization were defined as the no-treatment group. A patient's illness severity was measured and compared with other patients in the data set. Results. A total of 44,108 patients were assigned to the treatment group, and 14,255 patients were assigned to the no-treatment group. In general, longer lengths of stay and higher institutional costs were associated with the no-treatment group. Patients in the no-treatment group consistently displayed more comorbid conditions than did patients in the treatment group. The no-treatment group exhibited higher usage rates of both fibrinolytic agents and vitamin K. More patients in the treatment group were discharged to home or rehabilitation, while more patients in the no-treatment group were either discharged to another nursing facility or died before discharge. Conclusion. A retrospective analysis of a large national hospital database revealed that one quarter of patients who suffered an acute stroke did not receive antiplatelet drugs during their patient stay. Outcomes for such patients were poorer than for patients who had received antiplatelet therapy.

Introdução. A dupla antiagregação plaquetária traz benefícios no tratamento do infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMSST). Há variabilidade intra e interindividual no uso do clopidogrel e isso influencia no benefício do seu uso nesse grupo de pacientes. O objetivo desta pesquisa foi avaliar os efeitos de novo antiagregantes plaquetários (prasugrel e ticagrelor) administrados na sala de emergência (\"upstream\") sobre o resultado angiográfico da angioplastia primária, levando em conta o fluxo coronariano TIMI, o blush miocárdico e a carga de trombo. Métodos. Foi realizado um ensaio clínico, randomizado, cego, com 131 pacientes admitidos com IAMSST. Todos os pacientes receberam ácido acetilsalicílico (AAS). Os pacientes foram randomizados para receber clopidogrel (n=44), prasugrel (n=41) ou ticagrelor (n=46) como dose de ataque ainda na emergência. Todos os pacientes foram submetidos a aspiração manual de trombos. Ao término do procedimento, o resultado angiográfico foi avaliado quanto ao fluxo TIMI, o blush miocárdico e a carga de trombo. Resultados. O fluxo coronariano TIMI >= 1 antes do procedimento foi observado mais frequentemente com o uso de ticagrelor (n = 10, 21,7%) do que com o clopidogrel (n = 1, 2,3%) e prasugrel (n = 5, 12,2%; p = 0,019). O fluxo TIMI coronária no fim do procedimento não diferiu significativamente entre os grupos (p = 0,101). Melhor resultado no que diz respeito ao blush miocárdico foi observada com prasugrel, que produziu um grau de blush III em 85,4% (n = 35) dos pacientes, em comparação com o clopidogrel (54,5%; n = 24) e ticagrelor (67,4%; n = 31; p = 0,025). A carga de trombo pré-procedimento foi maior no grupo de clopidogrel, em que 97,7% (n = 43) dos casos denotaram carga de trombo grau 4/5, enquanto 87,8% (n = 36) do grupo prasugrel tiveram respostas semelhantes, e 80,4% (n = 37) foram observadas no grupo ticagrelor (p = 0,03). Conclusão. Os novos antiagregantes plaquetários ticagrelor e prasugrel parecem exercer efeito sobre o resultado angiográfico dos pacientes submetidos a angioplastia primária. O uso do ticagrelor propiciou menor carga de trombo e um fluxo TIMI melhor no pré-procedimento e o uso do prasugrel ensejou melhor perfusão miocárdica analisada pelo blush miocárdico. Não houve diferença no fluxo angiográfico TIMI pós procedimento / Introduction. Dual antiplatelet therapy has benefits in the treatment of acute myocardial infarction with ST-segment elevation (STEMI). There is variability intra and inter individual in the use of clopidogrel and this influences the benefit of its use in this group of patients. The objective of this research was to evaluate the angiographic results of Upstream Clopidogrel, Prasugrel, or Ticagrelor For Patients Treated With Primary Angioplasty. Methods. A clinical trial was conducted, randomized, double blind, with 131 patients admitted with STEMI. All patients received acetylsalicylic acid (ASA). Patients were randomized to receive clopidogrel (n = 44), prasugrel (n = 41) or ticagrelor (n = 46) as loading dose even in emergency. All patients were submitted to manual thrombus aspiration. At the end of the procedure, the angiographic result was evaluated for TIMI flow, myocardial blush and thrombus burden. Results. A coronary TIMI flow >= 1 before the percutaneous procedure was observed more frequently with the use of ticagrelor (n=10, 21.7%) than with clopidogrel (n=1, 2.3%) and prasugrel (n=5, 12.2%; p=0.019). The coronary TIMI flow at the end of the procedure did not significantly differ between the groups (p=0.101). A better result with respect to myocardial blush was observed with prasugrel, which yielded a blush grade of III in 85.4% (n=35) of patients, compared with clopidogrel (54.5%; n=24) and ticagrelor (67.4%; n=31; p=0.025). The pre-procedural thrombus burden was found to be of a higher grade in the clopidogrel group, in which 97.7% (n=43) of the cases exhibited thrombus burdens grade 4/5, whereas 87.8% (n=36) of the prasugrel group had similar responses, and 80.4% (n=37) were observed in the ticagrelor group (p=0.03). Conclusions. The novel antiplatelet agents represented by ticagrelor and prasugrel appear to have effect on the angiographic outcome of patients undergoing primary angioplasty. The use of ticagrelor led to a smaller thrombus burden and better TIMI flow at the beginning of the procedure and the use of prasugrel produced a better myocardial perfusion analyzed by myocardial blush. There was no difference in post angioplasty TIMI flow

Introdução. A dupla antiagregação plaquetária traz benefícios no tratamento do infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMSST). Há variabilidade intra e interindividual no uso do clopidogrel e isso influencia no benefício do seu uso nesse grupo de pacientes. O objetivo desta pesquisa foi avaliar os efeitos de novo antiagregantes plaquetários (prasugrel e ticagrelor) administrados na sala de emergência (\"upstream\") sobre o resultado angiográfico da angioplastia primária, levando em conta o fluxo coronariano TIMI, o blush miocárdico e a carga de trombo. Métodos. Foi realizado um ensaio clínico, randomizado, cego, com 131 pacientes admitidos com IAMSST. Todos os pacientes receberam ácido acetilsalicílico (AAS). Os pacientes foram randomizados para receber clopidogrel (n=44), prasugrel (n=41) ou ticagrelor (n=46) como dose de ataque ainda na emergência. Todos os pacientes foram submetidos a aspiração manual de trombos. Ao término do procedimento, o resultado angiográfico foi avaliado quanto ao fluxo TIMI, o blush miocárdico e a carga de trombo. Resultados. O fluxo coronariano TIMI >= 1 antes do procedimento foi observado mais frequentemente com o uso de ticagrelor (n = 10, 21,7%) do que com o clopidogrel (n = 1, 2,3%) e prasugrel (n = 5, 12,2%; p = 0,019). O fluxo TIMI coronária no fim do procedimento não diferiu significativamente entre os grupos (p = 0,101). Melhor resultado no que diz respeito ao blush miocárdico foi observada com prasugrel, que produziu um grau de blush III em 85,4% (n = 35) dos pacientes, em comparação com o clopidogrel (54,5%; n = 24) e ticagrelor (67,4%; n = 31; p = 0,025). A carga de trombo pré-procedimento foi maior no grupo de clopidogrel, em que 97,7% (n = 43) dos casos denotaram carga de trombo grau 4/5, enquanto 87,8% (n = 36) do grupo prasugrel tiveram respostas semelhantes, e 80,4% (n = 37) foram observadas no grupo ticagrelor (p = 0,03). Conclusão. Os novos antiagregantes plaquetários ticagrelor e prasugrel parecem exercer efeito sobre o resultado angiográfico dos pacientes submetidos a angioplastia primária. O uso do ticagrelor propiciou menor carga de trombo e um fluxo TIMI melhor no pré-procedimento e o uso do prasugrel ensejou melhor perfusão miocárdica analisada pelo blush miocárdico. Não houve diferença no fluxo angiográfico TIMI pós procedimento / Introduction. Dual antiplatelet therapy has benefits in the treatment of acute myocardial infarction with ST-segment elevation (STEMI). There is variability intra and inter individual in the use of clopidogrel and this influences the benefit of its use in this group of patients. The objective of this research was to evaluate the angiographic results of Upstream Clopidogrel, Prasugrel, or Ticagrelor For Patients Treated With Primary Angioplasty. Methods. A clinical trial was conducted, randomized, double blind, with 131 patients admitted with STEMI. All patients received acetylsalicylic acid (ASA). Patients were randomized to receive clopidogrel (n = 44), prasugrel (n = 41) or ticagrelor (n = 46) as loading dose even in emergency. All patients were submitted to manual thrombus aspiration. At the end of the procedure, the angiographic result was evaluated for TIMI flow, myocardial blush and thrombus burden. Results. A coronary TIMI flow >= 1 before the percutaneous procedure was observed more frequently with the use of ticagrelor (n=10, 21.7%) than with clopidogrel (n=1, 2.3%) and prasugrel (n=5, 12.2%; p=0.019). The coronary TIMI flow at the end of the procedure did not significantly differ between the groups (p=0.101). A better result with respect to myocardial blush was observed with prasugrel, which yielded a blush grade of III in 85.4% (n=35) of patients, compared with clopidogrel (54.5%; n=24) and ticagrelor (67.4%; n=31; p=0.025). The pre-procedural thrombus burden was found to be of a higher grade in the clopidogrel group, in which 97.7% (n=43) of the cases exhibited thrombus burdens grade 4/5, whereas 87.8% (n=36) of the prasugrel group had similar responses, and 80.4% (n=37) were observed in the ticagrelor group (p=0.03). Conclusions. The novel antiplatelet agents represented by ticagrelor and prasugrel appear to have effect on the angiographic outcome of patients undergoing primary angioplasty. The use of ticagrelor led to a smaller thrombus burden and better TIMI flow at the beginning of the procedure and the use of prasugrel produced a better myocardial perfusion analyzed by myocardial blush. There was no difference in post angioplasty TIMI flow

Clopidogrel is an antiplatelet drug prescribed to prevent stent thrombosis after a percutaneous coronary intervention (PCI). Previous evidence suggests that some widely prescribed statins may inhibit the antiplatelet effects of clopidogrel via competitive metabolism of its activating enzyme cytochrome P450 3A4 (CYP3A4). / The objective was to investigate the possibility of an interaction post-PCI between statins and clopidogrel. / We carried out a population-based cohort study identifying 10,491 patients using clopidogrel post-PCI (2001-2004). The outcome was a composite of death of any cause, myocardial infarction, unstable angina, repeat revascularization, and cerebrovascular events. We found that co-prescription of CYP3A4-metabolized statins (hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.79-1.15), or non-CYP3A4-metabolized statins (HR 0.82, 95% CI 0.63-1.07) with clopidogrel was not associated with increase in adverse outcomes. / We observed no evidence of interaction between clopidogrel and statins in a large population cohort of PCI patients, suggesting unlikelihood of an important interaction.

FundaÃÃo de Amparo à Pesquisa do Estado do Cearà / CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O gÃnero Lonchocarpus à bastante conhecido e amplamente estudado, porÃm nÃo hà registros na literatura cientÃfica dos usos farmacolÃgicos da espÃcie Lonchocarpus sericeus (Poir.) Kunth, (Leguminosae Papilionaceae). Estudos quÃmicos demonstraram que a fraÃÃo hexÃnica das cascas das raÃzes de L. sericeus (FLS) à rica nas chalconas: lonchocarpina (LCC) e derricina (DRC). O objetivo deste trabalho foi investigar os efeitos tÃxicos e as aÃÃes farmacolÃgicas da FLS e de sua chalconas LCC e DRC. A DL50 para FLS em camundongos foi de 781,5 mg/kg por v.o. e 446,2 mg/kg, por via i.p. A FLS e a DRC mostraram efeito inibitÃrio concentraÃÃo-dependente sobre o desenvolvimento embrionÃrio de ovos de ouriÃo-do-mar Lytechinus variegatus. A FLS, LCC e DRC apresentaram ainda atividade citotÃxica sobre cÃlulas de leucemia linfocÃtica de origem humana. A FLS, administrada por via sistÃmica, apresentou atividade antiedematogÃnica nos modelos de edema de pata induzidos por carragenina (Cg) e levedura de cerveja, mas nÃo sobre aqueles induzidos por dextrano ou bradicinina. O efeito da FLS no edema por Cg nÃo foi modificado pela associaÃÃo com a indometacina ou L-NAME, mostrando que a mesma parece nÃo interferir com a via da COX ou do sistema NO. Entretanto, este efeito da FLS foi potencializado pela pentoxifilina (PTX) evidenciando uma possÃvel inibiÃÃo da FDE e/ou da sÃntese de citocinas inflamatÃrias como o TNF-alfa. Apesar de ter inibido significativamente a migraÃÃo de neutrÃfilos na cavidade peritoneal de ratos induzida por Cg, a FLS apresentou um efeito inibitÃrio bem maior sobre Ãquela induzida por fMLP, demonstrando que a mesma alÃm de bloquear a sÃntese e/ou liberaÃÃo de mediadores inflamatÃrios como PGs, LTs e citocinas, pode tambÃm bloquear uma das etapas da migraÃÃo ou ainda, inibir alguma das molÃcula de adesÃo envolvidas neste processo. A FLS tambÃm reduziu o dano tissular induzido por Ãcido acÃtico em ratos, evidenciado atravÃs de seu efeito inibitÃrio sobre a atividade da MPO. Entretanto, a mesma nÃo foi capaz de suprimir a formaÃÃo do tecido de granulaÃÃo, induzida por pellet de algodÃo, onde as PGs desempenham um papel essencial. A atividade antinociceptiva da FLS tambÃm foi observada em modelos experimentais de dor como teste das contorÃÃes abdominais induzidas pelo Ãcido acÃtico e teste da formalina, em camundongos. Todavia, a FLS nÃo modificou a resposta nociceptiva ao estÃmulo tÃrmico no teste da placa quente. Este efeito antinociceptivo da FLS independe do sistema opiÃide e da via do NO, e tambÃm nÃo envolve a participaÃÃo do componente adrÃnergico, porÃm alÃm de outros mecanismos, a inibiÃÃo da FDE e/ou da sÃntese de citocinas como TNF-alfa parecem exercer um papel importante na antinocicepÃÃo da FLS. A atividade antiagregante plaquetÃra da FLS, LCC e DRC tambÃm foi estudada e os resultados demonstraram que as mesmas possuem efeito inibitÃrio da agregaÃÃo in vitro em plasma humano rico em plaquetas, frente aos agonistas ADP, colÃgeno, trombina, Ãcido araquidÃnico e adrenalina. O efeito antiagregante plaquetÃrio da FLS, LCC e DRC foi potencializado pela PTX, um inibidor da fosfodiesterase de AMPc, mas nÃo pela L-arginina ou pelo Ãcido acetilsalicÃlico. Desta forma, a FLS possui atividade citotÃxica, antiinflamatÃria, analgÃsica e antiagregante plaquetÃria. Estes efeitos parecem ser mediados pelas chalconas LCC e DRC, presentes na FLS. / The Lonchocarpus genus is well known and much studied though there is no record on scientific publications about the pharmacological properties of the species Lonchocarpus sericeus (Poir.) Kunth, (Leguminosae Papilionaceae). Chemical research determined that the hexanic fraction from root bark of L. sericeus (FLS) is rich in two chalcones: lonchocarpin (LCC) and dericin (DRC). This workâs purpose was to investigate the toxical effects and the pharmacological actions of FLS and its chalcones LCC e DRC. The LD50 of FLS in mice was 781,5 mg/kg, p.o. and 446,2 mg/kg, i.p. FLS and DRC showed concentration-dependent inhibition on the development of the sea urchin Lytechinus variegatus eggs. Additionaly, FLS, LCC and DRC showed cytotoxic activity on human lymphocytic leukemia cells. Sistemically administered FLS demonstrated anti-edematogenic activity on carragenan (Cg)- and yeast-induced rat paw edema models, but did not show any effect on dextran- or bradikinin-induced rat paw edema models. The FLS effect on Cg model was not modified by treatment with indomethacin or L-NAME what implies that it seems not to affect COX or NO pathways. Notwithstanding, this FLS effect was indeed potentiated by pentoxifylline (PTX) suggesting a possible phosphodiesterase (PDE) or TNF-alfa like cytokines inhibition. Even though FLS significantly inhibited the Cg-induced neutrophil migration on peritoneal cavity of rats, it showed a even stronger inhibitory effect upon fMLP-induced neutrophil migration on peritoneal cavity. This demonstrates that FLS, besides blocking the synthesis or liberation of inflammation mediators such as PG, LT and cytokines can also block one of the migration steps or maybe some of the adhesion molecules involved. FLS also reduced tissue damage induced by acetic acid in rats, demonstrated by its ability to inhibit myeloperoxidase (MPO) activity. However, FLS was not capable of blocking cotton pellet induced granulation tissue formation, which is dependet on PG. FLS antinociceptive activity was observed in experimental pain models, such as the acetic acid-induced abdominal contractions and formalin test, both in mice. Nevertheless, FLS did not modify nociceptive response to thermic stimuli in the hot plate model. FLS antinociceptive effect does not depend on opioid or NO release, and equally is independent from adrenergic activity, though it seems to involve PDE and/or TNF-alfa and other cytokines inhibition. Anti-platelet activity of FLS, LCC and DRC was also studied and all of them showed in vitro platelet aggregation inhibition in platelet-rich human plasma, upon ADP, collagen, thrombin, arachidonic acid or adrenalin agonist addition. FLS, LCC and DRC anti-platelet effect was potentiated by PTX, a PDE inhibitor, but not by L-arginine or aspirin. In conclusion, FLS possess cytotoxic, anti-inflammatory, analgesic and anti-platelet activities. These effects seem to be mediated by the chalcones LCC e DRC, present in FLS.

No description available.

Noventa e seis pacientes com diabetes melito do tipo 2 foram randomizados para receberem ou não abciximab durante o implante eletivo de stent coronário, com o objetivo de determinar se esse inibidor da glicoproteína IIb/IIIa reduz a hiperplasia intimal intra-stent, avaliada pelo ultra-som intracoronário, aos seis meses de evolução. A análise volumétrica mostrou que o abciximab não reduz o volume de obstrução intra-stent nestes pacientes [41,3% (DP21,0%) versus 40,5% (DP18,3%), p=0,853]. / Ninety-six type 2 diabetics were randomly assigned to receive abciximab or no abciximab at the time of elective stent implantation to determine whether this IIb/IIIa glycoprotein inhibitor would reduce in-stent intimal hyperplasia, measured by intravascular ultrasound, at 6-month follow-up. Volumetric analysis showed that abciximab was not associated with a reduction of in-stent volume obstruction in diabetic patients [41.3% (DP21.0%) versus 40.5% (DP18.3%), p=0.853).

Noventa e seis pacientes com diabetes melito do tipo 2 foram randomizados para receberem ou não abciximab durante o implante eletivo de stent coronário, com o objetivo de determinar se esse inibidor da glicoproteína IIb/IIIa reduz a hiperplasia intimal intra-stent, avaliada pelo ultra-som intracoronário, aos seis meses de evolução. A análise volumétrica mostrou que o abciximab não reduz o volume de obstrução intra-stent nestes pacientes [41,3% (DP21,0%) versus 40,5% (DP18,3%), p=0,853]. / Ninety-six type 2 diabetics were randomly assigned to receive abciximab or no abciximab at the time of elective stent implantation to determine whether this IIb/IIIa glycoprotein inhibitor would reduce in-stent intimal hyperplasia, measured by intravascular ultrasound, at 6-month follow-up. Volumetric analysis showed that abciximab was not associated with a reduction of in-stent volume obstruction in diabetic patients [41.3% (DP21.0%) versus 40.5% (DP18.3%), p=0.853).