Clinical significance of residual platelet reactivity in patients treated with platelet P2Y12 inhibitors

Platelet P2Y₁₂ inhibitors have become an essential component of the treatment strategy for patients with acute coronary syndromes and patients undergoing percutaneous coronary intervention. It is now well-established that approximately 30% of patients treated with the P2Y₁₂ inhibitor clopidogrel display high residual platelet reactivity despite treatment. Patients with high on-treatment platelet reactivity have approximately 2–3-fold greater risk of adverse cardiovascular events and stent thrombosis than those without high platelet reactivity. Conversely, clopidogrel-treated patients with low platelet reactivity display approximately 1.7-fold increased risk of major bleeding. High platelet reactivity is uncommon during treatment with prasugrel and ticagrelor, which achieve a greater reduction in adverse cardiovascular events compared to clopidogrel in ACS patients treated with PCI. This is at the expense of an increase in spontaneous bleeding, however. Minor bleeding events, such as skin haematomas, are more common in prasugrel- and ticagrelor-treated patients that have particularly low platelet reactivity values. These minor bleeding events may occasionally prompt discontinuation of therapy, but their overall prognostic impact is uncertain. However, risk factors for bleeding tend to overlap with risk factors for adverse cardiovascular events. Therefore, patients with these minor bleeding events may also be at higher risk of adverse cardiovascular events, conferring a benefit from low platelet reactivity. Further work is needed to determine the optimal level of platelet reactivity in individuals by taking into account their risk of subsequent adverse cardiovascular events and bleeding.     

A brief review on experimental fluorosis

Fluoride (F) is a naturally occurring contaminant in the water. F is essential for normal maintenance of teeth and bones. However, prolonged exposure to high concentration of F is found to be deleterious to teeth, bones and other organs. Besides drinking water, F can enter the body through food, dental products, drugs and industrial emission. People living in areas where F contamination is much higher than the expected level, are found to suffer from not only teeth and bone problem but also other systems, including brain and its functions. Since animals respond to the toxic effects of F like human beings, the deleterious effects of F have been produced experimentally in animals in order to determine the mechanism involved in the action of F. The reports indicating the chronic harmful effects of F in teeth, bones, heart, liver, kidneys, gastrointestinal tract, lungs, brain, blood, hormones and biochemical parameters of experimental animals and in in vitro studies have been reviewed in this article. The neurotoxic action of F that produces chiefly learning and memory impairment has also been included. The review also points out the harmful effects of F on reproduction, its teratogenic action and in inducing premature ageing. Finally, the reports indicating a reversal of certain toxicities of F in experimental animals after withdrawal of its exposure has been included.     

冠状动脉旁路移植术后患者血小板高反应性的影响因素分析

目的 研究冠状动脉旁路移植术（CABG）后患者出现血小板高反应性（HTPR）的相关影响因素,旨在为术后用药提供参考。方法 选取2017年1月至2020年6月河南科技大学第一附属 医院成功完成 CABG,术后使用氯吡格雷、阿司匹林治疗的 144例患者作为研究对象,其中男 110例, 女 34例,年龄（55.85±7.18）岁,收集所有患者临床资料,按血小板聚集抑制率分为正常血小板反应性 （NTPR）组116例、HTPR组28例。计量资料组间比较采用独立样本t检验,计数资料组间采用χ2 检验或 Fisher确切概率法,单因素、多因素分析筛选患者 HTPR 的可能危险因素。结果 两组CABG患者年龄比较,差异有统计学意义（χ2 =19.153,P<0.001）。HTPR组术前血肌酐指标为（74.52±9.84）μmol/L, 低于 NTPR 组（83.68±13.47）μmol/L,差异有统计学意义（P<0.05）。两组 CABG 患者手术时间、24 h引流量比较,差异均有统计学意义（χ2 =8.329、12.758,P<0.05）。HTPR组血块动力（K）、血块强度（MAADP） 分别为（1.50±0.37）min、（49.84±6.28）mm,均高于NTPR组（1.21±0.24）min、（37.54±5.41）mm,血块动力 （Alpha）、血块强度（MAthrombin）、凝血综合指数（CI）、花生四烯酸（AA）抑制率分别为（69.47±2.41）°、 （64.24±2.51）mm、（1.85±0.54）、（63.28±18.63）%,均低于 NTPR 组（72.85±2.31）°、（66.86±2.74）mm、 （2.97±0.92）、（79.74±16.59）%,差异均有统计学意义（均P<0.05）。多因素分析发现,年龄、性别、AA抑 制率、血肌酐为 HTPR 的危险因素（均 P<0.05）。结论 年龄、性别、AA 抑制率、血肌酐为 CABG 术后患者出现HTPR的危险因素,需进行相应预防,以期减少患者HTPR发生风险。     

Effect of platelet agonists on airway reactivity and intrathoracic platelet accumulation

1 Intravenous infusion of platelet activating factor (Paf), adenosine diphosphate (ADP), collagen and the thromboxane-mimetic U46619 induced a dose-related accumulation of 111indium-labelled platelets into the thoracic region of anaesthetized guinea-pigs. 2 Intravenous infusion of Paf increased the reactivity of the airways to the spasmogen histamine. Such changes were not observed following treatment with ADP, collagen or U46619. 3 Paf-induced bronchial hyperreactivity is not secondary to pulmonary platelet recruitment, changes in basal lung function or cardiovascular changes. 4 Paf-induced bronchial hyperreactivity is not dependent upon the endogenous generation of ADP or thromboxane.     

Intake of aspirin prior to metamizole does not completely prevent high on treatment platelet reactivity

European Journal of Clinical Pharmacology - Metamizole can sterically inhibit aspirin (ASA) from binding to cyclooxygenase 1 (COX1). It is recommended that ASA should be taken 30 min prior to...     

血小板高反应性的遗传因素及其药物治疗策略的研究进展

抗血小板药物是目前治疗缺血性心脏病的常用药物,主要包括氯吡格雷、阿司匹林,但易发生氯吡格雷抵抗、阿司匹林抵抗,而它们同属于抗凝治疗后血小板高反应性的范畴。遗传因素对血小板高反应性的影响至关重要。目前对血小板高反应性的治疗策略主要以个体化抗血小板治疗为主,常用的药物包括替格瑞洛、αIIbβ3拮抗剂、中药。总结了血小板高反应性的遗传因素和治疗策略的研究进展,旨在为血小板高反应性的治疗提供临床参考。     

Dietary flavanols and platelet reactivity

Epidemiology studies suggest that the consumption of diets rich in flavonoids is associated with reduced risk of cardiovascular disease. Plant-derived foods and beverages, such as red wine, tea, grape and grape juice, cocoa and chocolate, can be rich in 1 particular class of flavonoid, the flavan-3-ols. There is now an increasing body of research that suggests that consuming flavanol-rich foods can positively affect hemostasis, through mechanisms that either directly affect platelet function or increase certain endothelium-derived factors that maintain platelet acquiescence or increase fibrinolysis. In this paper, we will review a series of in vivo studies on the effects of flavanol-rich cocoa and chocolate on platelet activation and platelet-dependent hemostasis. In addition, we will briefly review the body of literature with regard to other flavanol-rich foods and beverages, and possible mechanisms of action.     

A brief review of atropine effects on physiology and performance

Atropine's effects on the eye, visual functions, psychoactivity, and memory and learning are discussed from studies in both nonhuman primates and humans. These effects are discussed in terms of their peripheral and central mediations to provide background information for the behavioral pharmacologist.     

Direct compression high functionality excipient using coprocessing technique: a brief review

Tablets are still the most commonly used dosage form because of the ease of manufacturing, convenience in administration, accurate dosing and excellent stability. Direct compression is the preferred method for the preparation of tablets. However, it has been estimated that less than 20 percent of the active pharmaceutical ingredients (API) can be processed into tablets via direct compression since the majority of API lack the flow, cohesion or lubricating properties required for direct compression. Increasing trends toward direct compression suggests the need for development of high functional excipients. High functionality of excipients can be obtained by development of new excipients or by particle engineering of existing excipients. Particle engineering using coprocessing provides a way to obtain an excipient with high functionality. Coprocessed excipients are the mixture of two or more excipients interacting at sub-particle level; that can provide an excipient with improved functionality as well as masking undesirable properties. Coprocessing is very cost effective method of providing high functional excipient. The present review discusses the advantages of coprocessed excipients, role of material science in coprocessing, methods of coprocessing of excipients and properties of various coprocessed excipients available in the market.     

阿司匹林、氯吡格雷、西洛他唑对冠脉支架植入术后患者血小板高反应性的影响

目的探讨阿司匹林、氯吡格雷、西洛他唑对冠脉支架植入术后患者血小板高反应性的影响。方法选取2014年1月~2016年12月在我院接受冠状动脉支架术患者120例为观察对象,将患者按照随机数字表法分为观察组和对照组。对照组患者进行阿司匹林、氯吡格雷联合治疗。观察组患者在对照组的基础上联合西洛他唑进行治疗。比较两组的患者的治疗效果及血小板的活化和聚集指标。于术后6个月对两组患者进行随访,观察并统计两组患者有无临床并发症症状。结果术后第3天,观察组患者MPAR值为(45.32±13.41),对照组患者MPAR值为(51.68±11.62);观察组CD62P值为(10.09±12.32),对照组CD62P值为(13.28±9.37);观察组患者PAC-1值为(57.56±20.23),对照组患者PAC-1值为(63.17±18.60);观察组患者术后1年内发现不良心脑血管事件7例,总体发生率为11.6%,对照组患者术后1年发现不良心脑血管事件19例,总体发生率为31.7%,以上各组数据之间差异均具有统计学意义(P<0.05)。另外观察组患者术后1年内,临床并发症总体发生率于对照组相比,无明显差异。结论阿司匹林、氯吡格雷联合西洛他唑论治疗与传统阿司匹林联合氯吡格雷治疗相比抑制冠脉支架术后血小板活化和聚集效果更为显著,能够明显降低不良心脑血管事件发生率,而临床并发症发生率并未增加。     

临床药师参与1例经皮冠状动脉介入术后血小板高反应患者的抗血小板治疗

目的:探讨临床药师在个体化抗血小板治疗中的作用。方法:回顾性分析临床药师参与的1例经皮冠状动脉介入术后再发缺血事件的抗血小板治疗的案例。结果:临床药师通过患者的疾病、基因型、药物相关作用等因素从药学角度分析再发缺血事件的原因,并参与药物治疗和药学监护,协助临床医生为患者制定个体化抗血小板治疗方案。结论:利用基因检测技术,临床药师为患者实施个体化抗血小板治疗,保障患者用药的安全、有效。     

5-Fluorouracil radiation sensitization — A brief review

Summary 5-Fluorouracil (FUra) has emerged as the most promising clinical radiosensitizer now available. FUra's capacity to render human cells more sensitive to x-rays was established soon after its synthesis. However, the recognition that the drug's unusual pharmacology dictated explicit scheduling requirements in man was not realized until recently when work in the author's laboratory identified the extra-cellular drug concentration X time factors necessary to create the intra-cellular radiosensitive state. Subsequent clinico-pharmacologic investigations led to the realization that only prolonged continuous infusions combined with appropriately fractionated, cyclical radiation therapy would maximize the clinical utility of this approach. Infused FUra radiation-sensitization therapy reaches its maximum efficacy against the squamous-transitional cancers. This group of human malignancies comprises about 15% of all human cancers. Preliminary data also suggests substantial promise in the local/regional control of rectal and breast cancers. Infused FUra used as a radiosensitizer has the potential to eliminate the need for about 90% of all radical cancer surgery.     

A brief review on recent developments in animal models of schizophrenia

Number of patients suffering from schizophrenia is increasing daily, subsequently, increasing the need of proper medication to treat the symptoms and eventually improve the patients' condition. However, all the progress for designing or discovering medication comes to a standstill, as the symptomatic treatment can only be done in the patients, but performing clinical trials with all the possible candidate drugs in human beings and patients is unethical. Thus, the need arises for proper animal and non-human primate animal models of the disease, which would not only serve the purpose of understanding the disease in a better physiological setting, but also would allow the scientists to focus on developing a therapeutically effective and potent medication for treating this hazardous disease. This brief review article focuses on a few animal models which are generally used for carrying out studies on schizophrenic symptoms in research labs and industry worldwide. The paper also tries to validate the pre-clinically available models based on certain specified criteria like the predictive constructive and face validity. Thus, the paper gives guidance toward the mechanistic and traditional models of schizophrenia applying some of the newer principles and helps researchers in deciding a particular relevant model for their own purpose.     

Genetic polymorphisms of high platelet reactivity in Chinese patients with coronary heart disease under clopidogrel therapy

International Journal of Clinical Pharmacy - Background: The variability in the clinical response to clopidogrel treatment has been attributed to genetic factors, but the specific genes and other...     

A brief review of studies of piracetam in dyslexia

Several double-blind studies of the effects of piracetam in developmental dyslexia are reviewed. There is general agreement among studies that piracetam appears to improve reading performance.     

左氧氟沙星的不良反应

左氧氟沙星是临床广泛应用的抗菌药，用药期间可能出现的不良反应涉及消化系统、中枢神经系统、心血管系统、血液及内分泌系统等8大系统，包括恶心、呕吐、头晕、头痛、皮肤过敏反应等症状。本文对左氧氟沙星不良反应进行简要综述，旨在引起临床医生的重视，促进其合理应用。     

Theranostic CAR T cell targeting: A brief review

More than hundred years ago, Paul Ehrlich postulated that our immune system should be able to recognize tumor cells. Just recently, the development of check point inhibitors, bispecific antibodies, and T cells genetically modified to express chimeric antigen receptors (CARs) underlines the true power of our immune system. T cells genetically modified with CARs can lead to complete remission of malignant hematologic diseases. However, they can also cause life‐threatening side effects. In case of cytokine release syndrome, tumor lysis syndrome, or deadly side effects on the central nervous system, an emergency shut down of CAR T cells is needed. Targeting of tumor‐associated antigens that are also expressed on vital tissues require a possibility to repeatedly switch the activity of CAR T cells on and off on demand and to follow the treatment by imaging. Theranostic, modular CARs such as the UniCAR system may help to overcome these problems.     

PON1(rs662)基因多态性对冠脉介入治疗患者血小板高反应性的影响

目的：探讨PON1（rs662）基因多态性对冠脉介入治疗患者血小板高反应性的影响。方法：279例PCI术后患者,给予氯吡格雷75 mg·d^-1及阿司匹林100 mg·d^-1抗血小板治疗,服用5 d后空腹抽取静脉血,并检测血栓弹力图（TEG）。将氯吡格雷治疗后血小板高反应性（HPR）定义为二磷酸腺苷（ADP）诱导的血小板抑制率<50%。应用单因素和多因素回归分析PON1（rs662）基因多态性及临床因素对HPR的影响,利用受试者工作曲线（ROC curve）检验联合独立风险因素模型预测HPR的效力。结果：279例PCI术后患者HPR发生率为19.0%。多因素logistic回归分析示PON1（rs662） A等位基因（OR=2.101,95% CI=1.002~4.406,P=0.049）、糖尿病（OR=1.921,95% CI=1.023~3.604,P=0.042）为HPR的独立风险因素。联合独立风险因素模型预测HPR的曲线下面积（AUC）为0.680（95% CI=0.600~0.760,P<0.001）。结论：PON1（rs662） A等位基因及糖尿病为PCI术后患者HPR的独立危险因素。通过联合独立风险因素模型预测HPR的效力良好。