氯吡格雷抵抗与卒中防治

氯吡格雷是缺血性卒中治疗的基本药物,被多国卒中治疗指南所推荐,广泛应用于临床.有不少缺血性卒中患者在经过规范氯吡格雷治疗后仍然复发卒中,因此必须重视氯吡格雷抵抗现象.文章对氯吡格雷抵抗的生化机制、基因多态性、实验室检测及其应对措施进行了综述.     

缺血性卒中或短暂性脑缺血发作的双重抗血小板治疗

2013年美国心脏协会/美国卒中协会颁布的缺血性卒中早期处理指南推荐单用阿司匹林进行抗血小板治疗,并未推荐其他抗血小板药,更未推荐联合应用多种抗血小板药.然而,2013年之后发表的大量文献显示,双重抗血小板药在防治缺血性卒中和短暂性脑缺血发作方面优于单个抗血小板药,并评估了双重抗血小板药治疗的安全性.     

Additional N-glycosylation at Asn(13) rescues the human LHbeta-subunit from disulfide-linked aggregation

CG, LH, FSH, and TSH are a family of heterodimeric glycoprotein hormones that contain a common -subunit, but differ in their hormone-specific β-subunits. Despite the considerable homology between LHβ and CGβ, we previously demonstrated that, when expressed in GH₃ cells, the secreted form of LHβ showed mispaired disulfide-linked aggregation in addition to monomer, whereas no aggregation was observed in CGβ. To determine the domains which are associated with the LHβ-aggregation and which prevent CGβ-aggregation, mutant β-subunits in glycosylation and carboxy-terminus were expressed in GH₃ cells, and the occurrence of aggregation was assessed by continuous labeling with [³⁵S]methionine/cysteine, immunoprecipitation with anti-hCGβ serum, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis in a non-reducing condition. No aggregation was seen when N-linked oligosaccharides were attached to the Asn¹³ of LHβ. Removal of the carbohydrate unit at the Asn¹³ of CGβ caused aggregation, although the amount was less than 10% of monomer. The carboxy-terminal regions of neither LHβ nor CGβ were associated with their aggregation. Both CGβ wild-type (WT) and CGβ lacking N-glycosylation at Asn¹³ (CGβ-N13) showed aggregates in lysate. However, in contrast to CGβ-N13, CGβWT revealed no aggregation in medium. These results indicate that the backbone structure consisting of 114 amino acids and N-linked glycosylation at Asn³⁰ is involved in the aggregation of LHβ. Moreover, N-glycosylation at Asn¹³ does not prevent such aggregation, but instead plays an important role in correct folding for both LHβ- and CGβ-subunits to be secreted as monomer.     

Cardiac Genetic Predisposition in Sudden Infant Death Syndrome

Background

Sudden infant death syndrome (SIDS) is a leading cause of postneonatal mortality. Genetic heart diseases (GHDs) underlie some cases of SIDS.

红葡萄酒及白藜三醇对血小板聚集的影响

观察红葡萄酒及其提取物白藜三醇对离体和在体条件下血小板聚集的影响 ,以探讨它们对心血管系统的保护作用机制。以高胆固醇饮食造成实验性高脂血症 ,以凝血酶、二磷酸腺苷和胶原为诱导剂 ,采用Born氏法测定血小板聚集率。结果发现 ,高脂饮食明显增加兔血浆胆固醇水平 ,并伴有血小板聚集的明显增强。同时给予红葡萄酒、去酒精红葡萄酒和白藜三醇可以消除高脂饮食对兔血小板聚集的增强作用。离体条件下白藜三醇明显抑制凝血酶、二磷酸腺苷及胶原诱导的健康人的血小板聚集。结果提示 ,红葡萄酒及白藜三醇均具有抑制血小板聚集的作用 ,此作用可能为白藜三醇抗动脉粥样硬化的机制之一。     

Antiplatelet effects of aspirin with phytosterols: Comparison with non-enteric coated aspirin alone

The novel combination of aspirin and phytosterols may be a potential strategy to treat patients with cardiovascular disease. We sought to determine if the antiplatelet effects of a combination caplet of 81 mg aspirin with 400 mg phytosterols differed from the antiplatelet effects of non-enteric coated aspirin. The first five days of aspirin therapy alone (T1) produced marked reductions in collagen-induced, ADP-induced, and archidonic acid- induced platelet aggregation, and in serum and urine TxB₂ compared to baseline. Five days after randomization to aspirin alone versus aspirin + phytosterols (T2), there were no differences in any measurement of platelet function within each group compared to T1 or between groups. The present study suggests that the antiplatelet effect of non-enteric coated 81 mg twice-daily aspirin therapy alone is not affected by the addition of phytosterols in a combination product.     

粘性放线菌Ⅱ型菌毛粘附与凝集活性的研究

目的:研究粘放菌Ⅱ型菌毛在细菌粘附与凝集过程中的作用。方法:制备粘放菌Ⅱ型菌毛多克隆抗体抗血清,检其对粘放菌变异株5519、5951、T14V的粘附抑制率,同时肉眼观察它对粘放菌与血链菌34间凝集反应的影响。结果:抗Ⅱ型毛多克隆抗体能减少5519、5951、T14V对玻壁的粘附量,并抑制5951、T14V与血链菌34间的凝集反应。结论:粘放菌Ⅱ型菌具有粘附与凝集的活性。     

ROLE OF SURFACTANT PROTEIN A (SP-A)/LIPID INTERACTIONS FOR SP-A FUNCTIONS IN THE LUNG

Surfactant protein A (SP-A), an oligomeric glycoprotein, is a member of a group of proteins named collectins that contain collagen-like and Ca 2+ -dependent carbohydrate recognition domains. SP-A interacts with a broad range of amphipathic lipids (glycerophospholipids, sphingophospholipids, glycosphingolipids, lipid A, and lipoglycans) that are present in surfactant or microbial membranes. This review summarizes SP-A/lipid interaction studies regarding the lipid system used (i.e., phospholipid vesicles, phospholipid monolayers, and lipids immobilized on silica or adsorbed on a solid support). The effect of calcium, ionic strength, and pH on the binding of SP-A to lipids and the subsequent lipid aggregation process is discussed. Current evidence suggests that hydrophobic-binding forces are involved in the peripherical association of SP-A to membranes. It is also proposed that fluid and liquid-ordered phase coexistence in surfactant membranes might favor partition of SP-A into those membranes. The binding of SP-A to surfactant membranes containing hydrophobic surfactant peptides makes possible the formation of a membrane reservoir in the alveolar fluid that is protected by SP-A against inactivation and improves the rate of surfactant film formation. In addition, the interaction of SP-A with membranes might enhance the affinity of SP-A for terminal carbohydrates of glycolipids or glycoproteins on the surface of invading microorganisms.     

Ethanol stimulates prostacyclin biosynthesis by human neutrophils and potentiates anti-platelet aggregatory effects of prostacyclin

Previous reports on the direct effects of ethanol on human platelet aggregation function have been inconsistent. Ethanol ingestion produces vasodilation and raises intracellular cyclic AMP concentrations, effects similar to those of prostacyclin. We, therefore, hypothesized that ethanol may influence biosynthesis and/or bioactivity of prostacyclin. In our experiments, ethanol in concentrations up to 400 mg% had no consistent inhibitory effect on platelet aggregation in response to epinephrine, ADP, or combination of subthreshold concentrations of epinephrine plus ADP. However, ethanol in concentrations as low as 10 mg% potentiated the platelet aggregation inhibitory effects of prostacyclin. In addition, ethanol (20 mg%) decreased formation of thromboxane A₂ in whole blood by 41% and stimulated formation of prostacyclin by 160% (both P c 0.01). Additional studies using isolated human cells demonstrated synthesis of prostacyclin by neutrophils in the presence of platelets, and this neutrophil prostacyclin formation was enhanced in the presence of ethanol. These effects of alcohol in concentrations achieved after moderate intake may relate to the hemodynamic, biochemical, and cardioprotective effects of ethanol.     

刺参酸性黏多糖(SJAMP)对血小板三磷酸腺苷(ATP)释放的影响

目的 :研究刺参酸性黏多糖 (SJAMP)对正常人血小板三磷酸腺苷 (ATP)释放的影响 ,以进一步了解其释放机制。方法 :利用Chrono log 60 0型血小板荧光 聚集仪 ,对SJAMP诱导的血小板聚集及ATP释放反应进行同步测定。结果 :SJAMP诱导人血小板的聚集为典型的 Ⅱ 相聚集 ,在血小板聚集和释放间存在一定的延迟期 ,其释放反应依赖于血小板的聚集 ,并且血小板的释放反应能够为环氧化酶抑制剂乙酰水杨酸 (ASA)所抑制。不同诱聚剂SJAMP 10 0 μg/ml,ADP5 μmol/L ,胶原 5mg/ml,作用于人PRP后的ATP释放分别为 0 69± 0 2 2nmol/10 8血小板、1 60± 0 2 5nmol/10 8血小板、1 5 7± 0 15nmol/10 8血小板。SJAMP诱导正常人ATP释放量明显低于ADP、胶原等诱导的ATP释放量 (P <0 0 1)。结论 :从诱导血小板释放的角度 ,SJAMP是比ADP更弱的一种血小板诱聚剂。