Platelet-Derived Extracellular Vesicles as Target of Antiplatelet Agents. What Is the Evidence?

Platelet-derived large extracellular vesicles (often referred to as microparticles in the field of cardiovascular disease) have been identified as effector in the atherothrombotic process, therefore representing a target of pharmacological intervention of potential interest. Despite that, limited evidence is so far available concerning the effects of antiplatelet agents on the release of platelet-derived extracellular vesicles. In the present narrative review, the mechanisms leading to vesiculation in platelets and the pathophysiological processes implicated will be discussed. This will be followed by a summary of the present evidence concerning the effects of antiplatelet agents under experimental conditions and in clinical settings

Fatty acids profile in meat of steers from different ages and genetic groups finished in feedlot

Foram utilizados 24 bovinos machos castrados, pertencentes a quatro grupos genéticos (⅝Charolês (CH) ⅜Nelore (NE); ⅝NE ⅜CH; ¾ CH ¼ NE e ¾ NE ¼ CH) e duas idades (jovem e superjovem), mantidos com dieta composta de silagem de milho e concentrado, com relação volumoso:concentrado de 50:50. As carcaças, após o abate, foram identificadas e resfriadas retirando-se um bife da porção do músculo Longissimus dorsi, que foi seco em estufa, moído, identificado e armazenado para extração dos lipídeos e determinação dos ácidos graxos, realizada em cromatógrafo a gás. Não houve interação significativa categoria × grupo genético para marmoreio, espessura de gordura e relação músculo:gordura, utilizados como co-variáveis. O total de ácidos graxos trans18 nos animais superjovens foi maior (2,46%) que nos jovens (1,87%). A maioria dos ácidos graxos de cadeia curta (75%) e de cadeia média (91,7%) não foi influenciada pelo grupo genético. Os valores de ácido linoléico conjugado (CLA) não diferiram entre os grupos genéticos. Animais com predominância Nelore apresentaram maior grau de saturação nos ácidos graxos (média de 54,7%) em comparação aos de predominância Charolês (média de 49,5%). A relação de ácidos graxos insaturados/saturados nos animais Charolês foi maior que nos animais Nelore.For the conduction of this work, 24 males from four different genetic groups (⅝Charolais (CH) ⅜Nellore (NE); ⅝NE ⅜CH; ¾CH ¼NE e ¾NE ¼CH) and two ages: steers and young steers were used. The animals received a diet composed of corn silage and concentrate with roughage:concentrate ratio of 50:50. After slaughter, the carcasses were identified and⅝ chilled. A steak from the longissimus muscle was collected and dried in stove, grounded, identified and stored for lipid extraction. The fatty acids (FA) determination was performed through gas chromatograph. No significant interaction was observed between category and genetic groups and marbling, fat thickness, muscle:fat ratio, used as co-variables. The total trans18 FA was higher (2.46%) for young steers in relation to steers (1.87%). Most short-chain (75%) and medium-chain (91.7%) FA were not influenced by the genetic group. CLA values did not differ between CH-NE crossbred animals. Animals with NE predominance showed higher saturated FA (average of 54.7%) in relation to CH animals (average of 49.5%). In relation to the unsaturated/saturated ratio, higher value was observed for CH animals

Calcium-Dependent Src Phosphorylation and Reactive Oxygen Species Generation Are Implicated in the Activation of Human Platelet Induced by Thromboxane A2 Analogs

The thromboxane (TX) A2 elicits TP-dependent different platelet responses. Low amounts activate Src kinases and the Rho–Rho kinase pathway independently of integrin αIIbβ3 and ADP secretion and synergize with epinephrine to induce aggregation. Aim of the present study was to investigate the role Src kinases and the interplay with calcium signals in reactive oxygen species (ROS) generation in the activatory pathways engaged by TXA2 in human platelets. All the experiments were performed in vitro or ex vivo. Washed platelets were stimulated with 50–1000 nM U46619 and/or 10 μM epinephrine in the presence of acetylsalicylic acid and the ADP scavenger apyrase. The effects of the ROS scavenger EUK-134, NADPH oxidase (NOX) inhibitor apocynin, Src kinase inhibitor PP2 and calcium chelator BAPTA were tested. Intracellular calcium and ROS generation were measured. Platelet rich plasma from patients treated with dasatinib was used to confirm the data obtained in vitro. We observed that 50 nM U46619 plus epinephrine increase intracellular calcium similarly to 1000 nM U46619. ROS generation was blunted by the NOX inhibitor apocynin. BAPTA inhibited ROS generation in resting and activated platelets. Phosphorylation of Src and MLC proteins were not significantly affected by antioxidants agents. BAPTA and antioxidants reduced P-Selectin expression, activation of integrin αIIbβ3and platelet aggregation. TXA2-induced increase in intracellular calcium is required for Src phosphorylation and ROS generation. NADPH oxidase is the source of ROS in TX stimulated platelets. The proposed model helps explain why an incomplete inhibition of TP receptor results in residual platelet activation, and define new targets for antiplatelet treatment

QUALIDADE DA CARCAÇA E DA CARNE DE NOVILHOS ABATIDOS COM PESOS SIMILARES, TERMINADOS EM DIFERENTES SISTEMAS DE ALIMENTAÇÃO

O objetivo deste trabalho foi estudar as características qualitativas da carcaça e da carne de novilhos Aberdeen Angus terminados em confinamento, com canade-açúcar + concentrado, ou em pastagem cultivada de azevém (Lolium multiflorum) + sal comum como suplemento mineral. Abateram-se os novilhos aos 24 meses de idade com pesos similares de 394 e 396 kg, respectivamente. Alimentaram-se os animais confinados com dieta contendo, na matéria seca, 72,3% de cana-de-açúcar e 27,7% de concentrado. Os novilhos apresentaram no início da terminação peso médio de 320 kg e idade média de vinte meses. Não houve diferença nas percentagens de músculo e de osso. A percentagem de gordura foi similar, sendo de 22,8% e 20,7%, respectivamente, para animais terminados em pastagem e confinamento. A suculência, o sabor, a força de cisalhamento e a quebra no descongelamento mostraram-se maiores nos animais terminados em pastagem cultivada, sendo, respectivamente, 6,93 pontos, 6,60 pontos, 9,23 kgf e 8,28%, contra 5,93 pontos, 5,77 pontos, 7,27 kgf e 5,27%, na mesma ordem, para novilhos alimentados em confinamento. Contudo, outras características qualitativas da carne como cor, textura, marmoreio, maciez e quebra na cocção foram similares entre os tratamentos. PALAVRAS-CHAVE: Aberdeen Angus, cana-de-açúcar, confinamento, pastagem hibernal

Effects of antiangiogenetic drugs on microcirculation and macrocirculation in patients with advanced-stage renal cancer

Adverse cardiovascular effects, including hypertension, were described in patients with different cancers treated with tyrosine kinase inhibitors (TKI). The mechanism of TKI-related hypertension is still debated. The aim of this work was to study the effects of TKI on blood pressure (BP), searching for a relationship with possible causative factors in patients with metastatic renal cell carcinoma. We included 29 patients in a prospective, observational study; 22 were treated with a first-line drug (sunitinib), while seven participated in the second-line treatment (axitinib or cabozantinib). Patients were investigated at the beginning of antiangiogenic therapy (T0) and at one (T1), three (T2), and six months (T3) after treatment. Patients were evaluated by office blood pressure (BP) and ultrasonography to measure flow-mediated dilatation (FMD), and carotid artery distensibility (cDC) by echocardiography and nailfold capillaroscopy. Plasma endothelin-1 (p-ET-1), urine nitrates, and proteins were also measured. At T1, systolic BP, along with U proteins and p-ET-1, increased significantly. In patients with a clinically significant increase in BP (defined as either the need for an antihypertensive drug or systolic blood pressure (SBP) T1\u207bT0 6510 and/or SBP 65140 mmHg and/or diastolic blood pressure (DBP) T1\u207bT0 655 and/or DBP 6590 mmHg), the urine nitrate concentration was lower at T0, whereas there were no differences in the p-ET-1 and U proteins. Seventeen participants showed changes in the capillaroscopic pattern at T1 with no association with BP increases. There were no differences in the FMD, cDC, and echocardiographic parameters. Our findings are consistent with those of previous studies about BP increases by TKI, and suggest a role of nitric oxide in BP maintenance in this population

Inibitori della cicloossigenasi e cardiopatia ischemica

trattazione rischio cardiovascoalre associato a uso di FAN