血小板膜糖蛋白和血小板聚集率变化与冠心病的临床意义

目的观测冠心病(CHD)患者血小板膜糖蛋白(GP)、血小板最大聚集率(PAgT)、血脂水平的变化及相关性。方法选择CHD患者122例,其中稳定性心绞痛(SAP)患者54例(SAP组),不稳定性心绞痛(UAP)患者68例(UAP组),另选健康体检者48例(对照组)。又根据有无冠状动脉事件分为心血管事件组(57例)和无心血管事件组(65例)。测定各组血GP、PAgT及血脂水平。结果 UAP组患者GP、PAgT水平明显高于对照组及SAP组患者。心血管事件组GP、PAgT也明显高于无心血管事件组;SAP组患者血小板表面α颗粒GP-140、PAgT水平明显高于对照者;回归分析发现,CHD患者PAgT水平与GP、LDL-C、脂蛋白(a)呈正相关。结论 PAgT水平升高是CHD患者冠状动脉事件发生的重要因素,高脂血症可以促进血小板在冠状动脉硬化过程中的活化。     

Fibrogenic cell phenotype modifications during remodelling of normal and pathological human liver in cultured slices

Background: The debate concerning the potential remodelling and/or reversibility of cirrhotic lesions and biliary fibrosis is still open. Aims/Methods: In this work, we have used the precision‐cut liver slice (PCLS) model, which maintains cell–cell and cell–matrix interactions to study, by immunohistochemistry, the behaviour of the different fibrogenic cells, i.e. hepatic stellate cells (HSC) and portal fibroblasts, in cultured (for 1 week) PCLS derived from normal and fibrotic human livers. Results: In normal liver, before and after culture, α‐smooth muscle (SM) actin was present only in the vessel walls. Platelet‐derived growth factor (PDGF) receptor‐β was expressed before and after culture by portal fibroblasts, and appeared after culture in HSC. Before culture, CD 34 was not expressed in parenchyma, but appeared after culture in sinusoidal endothelial cells. In cirrhotic lesions, before culture, α‐SM actin, PDGF receptor‐β and Thy‐1 were expressed in septa; after culture, α‐SM actin expression disappeared but the expression of the PDGF receptor‐β and Thy‐1 was maintained. In cholestatic liver specimens, α‐SM actin, PDGF receptor‐β and Thy‐1 expression, which was present before culture in enlarged portal areas, disappeared after culture, and apoptosis was detected. In the parenchyma of both cirrhotic and cholestatic livers, the expression of the PDGF receptor‐β and of CD 34, which was not observed before culture, was present in HSC and sinusoidal endothelial cells, respectively, after culture. Conclusions: These results indicate that during remodelling of pathological tissues in cultured liver slices, the myofibroblastic cells derived from HSC or from portal fibroblasts show different behaviours, suggesting different mechanisms of activation/deactivation.     

重症患者血小板输注的临床研究

目的：探明重症患者血小板（PLT）减少的发生率及PLT输注的目的、指征、效果以及血小板减少对患者预后的影响。方法：采用回顾性方法分析临床资料,血小板减少定义为PLT〈100×109/L,根据PLT减少的程度分为轻度减少,PLT〈100×109/L;中度减少,PLT〈50×109/L;重度减少,PLT〈20×109/L。结果：53.4%（206例）重症患者住院期间曾出现PLT〈100×109/L,与PLT未减少患者相比PLT减少患者有较高的死亡率（P〈0.05）,需要输注较多的血小板（P〈0.05）、新鲜冰冻血浆（P〈0.05）和红细胞（P〈0.05）。结论：约50%重症监护病房住院患者在住院过程中出现过PLT〈100×109/L,血小板减少患者需要较多的输血支持,有较高的死亡率。     

新型振荡注射仪在冰冻血小板中的应用研究

目的：研究手工法与某新型振荡注射仪冰冻血小板之异同。方法：通过手工法及与某厂家合作研制的振荡注射仪冰冻血小板,检测2组血小板冰冻前后的关键指标及临床应用指标,并比较2者之间的差异。结果：手工组和振荡注射仪组在加入DMSO后冰冻前与对照组比较,在血小板P选择蛋白和PF4方面差异有统计学意义（P〈0.01）,在加入DMSO冰冻后复溶与对照组比较,血小板黏附功能、血小板P选择蛋白、血小板第4因子（PF4）和血块收缩试验之间差异有统计学意义（P〈0.01）,但手工组与振荡注射仪组之间差异无统计学意义（P〉0.05）,振荡注射仪组与手工组在融化后报废率方面差异有统计学意义（P〈0.01）。结论：振荡注射仪组在融化后报废率方面优于手工组。     

Antithrombotic therapy in the elderly

Antithrombotic therapy represents the mainstay of treatment for prevention of recurrent ischemic events in patients with atherothrombotic disease processes. Although the benefits of antithrombotic pharmacotherapy in the elderly are well established, the elderly are generally more vulnerable to the adverse effects of antithrombotic drugs. Such higher vulnerability may be related to distinct pharmacokinetic and pharmacodynamic responses in the late age of life, during which drug-drug interactions due to polypharmacy further enhance the risk of adverse effects associated with the use of antithrombotic agents. Given that the prevalence of atherothrombotic disease, as well as diseases with thromboembolic potential, increases exponentially with age and that the elderly population is in continuous growth, understanding strategies of antithrombotic management in these patients is of key importance. The present paper provides an overview of the current available evidence on the use of antithrombotic therapy in elderly patients with the primary focus on treatment of coronary artery disease.     

加味柴胡温胆汤对老年高血压患者血小板活化状态及颈动脉内膜厚度的影响

目的:探讨加味柴胡温胆汤抗动脉硬化的作用及其机制。方法:将入选老年高血压患者随机分成3组:阿托伐他汀组(A组)、加味柴胡温胆汤组(C组)、阿托伐他汀组+加味柴胡温胆汤组(A+C组)。在常规降压药物基础上,A组予以阿托伐他汀20 mg.d-1口服,C组予以加味柴胡温胆汤20 g/次,全天3次随三餐前或后口服,A+C组同时口服阿托伐他汀和加味柴胡温胆汤,剂量和方法与A,C组相同。患者入选时(记为0点)和服药满12个月(记为12点)、18个月时(记为18点)均分别用放射免疫法检测血浆血小板α颗粒膜蛋白(GMP)-140,超声检测左侧颈总动脉内膜-中层厚度(IMT)。结果:关于GMP-140值:C组、A+C组在12点和18点显著低于0点和A组(P<0.01);C组和A+C组在12点、18点无明显统计学差别。A组在18点方显示低于0点(P<0.05)。关于IMT值:在12点,C组和A+C组明显低于0点和A组(P<0.01);C组和A+C组无统计学差别;而A组较0点无降低。在18点,C组和A+C组仍明显比A组低(P<0.01);C组和A+C组仍无统计学差别;3组IMT均明显低于0点和12点(P<0.01)。结论:加味柴胡温胆汤可以抑制血小板活化,并抑制老年高血压患者动脉硬化进程。     

Comparison of the function of the serotonin transporter in the vasculature of male and female rats

1. The serotonin transporter (SERT) handles serotonin (5‐hydroxytryptamine (5‐HT)) and is blocked by the antidepressant SERT inhibitors fluoxetine and fluvoxamine. Although the importance of SERT in the central nervous system is clear, SERT also functions in the peripheral vasculature. In the present study, we tested the hypothesis that the vasculature from female rats has increased SERT function compared with male rats because females are more responsive to SERT inhibitors. 2. In addition to in vitro experiments, in vivo experiments were used to evaluate how male and female rats handle chronically elevated levels of 5‐HT. Wild‐type (WT) and SERT‐knockout (SERT‐KO) rats were infused with 5‐HT (25 μg/kg per min) for 7 days by minipump. 3. Using HPLC analysis, we demonstrated that blood vessels (aorta, carotid artery, jugular vein and vena cava) from naïve, non‐infused female rats took up 5‐HT acutely in vitro in a SERT‐dependent manner. In in vitro experiments, SERT affected the contractility of aortas from female rats, as evidenced by an eightfold increase in potency of 5‐HT in fluvoxamine (1 μmol/L)‐incubated WT aortas compared with control. Fluvoxamine did not alter 5‐HT‐induced contraction in aortas from SERT‐KO female rats. 4. Infusion of 5‐HT resulted in an increase in tissue 5‐HT that was reduced to a larger extent in blood vessels from female than male SERT‐KO rats. Aortic contractions to 5‐HT were abolished in aortas from male and female 5‐HT‐infused SERT‐KO rats compared with WT rats. 5. Collectively, these data suggest that SERT function, when challenged with 5‐HT, is modestly more important in the vasculature of the female compared with male rat.     

Anti-platelet therapy: phosphodiesterase inhibitors

Inhibition of platelet aggregation can be achieved either by the blockade of membrane receptors or by interaction with intracellular signalling pathways. Cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) are two critical intracellular second messengers provided with strong inhibitory activity on fundamental platelet functions. Phosphodiesterases (PDEs), by catalysing the hydrolysis of cAMP and cGMP, limit the intracellular levels of cyclic nucleotides, thus regulating platelet function. The inhibition of PDEs may therefore exert a strong platelet inhibitory effect. Platelets possess three PDE isoforms (PDE2, PDE3 and PDE5), with different selectivity for cAMP and cGMP. Several nonselective or isoenzyme-selective PDE inhibitors have been developed, and some of them have entered clinical use as antiplatelet agents. This review focuses on the effect of PDE2, PDE3 and PDE5 inhibitors on platelet function and on the evidence for an antithrombotic action of some of them, and in particular of dipyridamole and cilostazol.