急性非致残性缺血性脑血管事件高危人群CYP2C19基因多态性与氯吡格雷抵抗的关系

目的 探讨急性非致残性缺血性脑血管事件高危人群CYP2C19基因多态性与氯吡格雷抵抗的关系。方法 选取2020年1月至2021年3月就诊于九江市第一人民医院的160例急性非致残性缺血性脑血管事件高危人群作为研究对象,采用京因药物基因床旁检测系统来实现CYP2C19基因床边快速检测,依据CYP2C19基因位点分为快代谢组64例、中间代谢组76例、慢代谢组20例。比较不同代谢基因组患者的血小板ADP抑制率及氯吡格雷抵抗情况的差异。结果 不同代谢基因组中氯吡格雷抵抗率情况比较,差异无统计学意义（P>0.05）;不同代谢基因组血小板ADP抑制率比较,差异无统计学意义（P>0.05）。结论 对于服用氯吡格雷的急性非致残性缺血性脑血管事件高危人群的患者,CYP2C19基因多态性与氯吡格雷抵抗尚不能确定有确切关联。     

老年冠心病患者氯吡格雷联用钙拮抗剂的疗效观察

目的：观察老年冠心病患者使用氯吡格雷（氯吡格雷）联用钙拮抗剂（CCB）的疗效。方法选取我院2010年1月～2013年5月收治的1142名有完整住院治疗资料和随访记录的老年冠心病患者进行回顾性分析,其中仅服用氯吡格雷进行治疗的患者有512例（A组）,服用氯吡格雷联用钙拮抗剂的患者有630例（B组）,B组患者中,有562例患者服用的是二氢吡啶类CCB,另外68例患者服用的是非二氢吡啶类CCB,通过对比观察其治疗效果。结果A组的发病密度为40.28/1000,B组患者的发病密度42.14/1000,粗RR为0.79[95% CI：（0.49-1.15）],调整后的RR为0.51[95% CI：（0.17-1.43）],两组的全因死亡率（P＞0.05）,差异无统计学意义,两组的终点事件发生率（P＞0.05）,差异无统计学意义。对两组患者进行混杂因素的倾向评分加权对比,服用二氢吡啶类CCB和服用非二氢吡啶类CCB的患者对比,OR=1.83[95% CI：（1.3-3.25）],差异有统计学意义（P＜0.05）。结论老年冠心病患者服用氯吡格雷联用钙拮抗剂进行治疗,不会使缺血性心脑血管事件以及全因死亡率增加,服用氯吡格雷联用二氢吡啶类CCB发生缺血性脑血管事件的机率,比服用氯吡格雷联用非二氢吡啶类CCB要低。     

阿托伐他汀联合氯吡格雷对急性缺血性脑卒中患者神经相关指标及血清Hcy、hs-CRP的影响

目的：探讨阿托伐他汀联合氯吡格雷对急性缺血性脑卒中患者神经相关指标及血清同型半胱氨酸(Hcy)和超敏C-反应蛋白(hs-CRP)的影响。方法：选取南阳市中心医院2020-06～2022-06急性缺血性脑卒中患者196例，随机分为对照组与研究组，各98例。对照组患者给予氯吡格雷治疗；研究组在氯吡格雷基础上口服阿托伐他汀治疗。两组治疗周期4周。比较两组治疗前后脑卒中患者神经功能缺损(NIHSS)评分，神经相关指标[神经元特异性烯醇化酶(NSE)和脑源性神经生长因子(BDNF)],Hcy和hs-CRP浓度及治疗疗效。结果：治疗后，两组脑卒中患者NIHSS评分较治疗前降低(P<0.05);且研究组脑卒中患者NIHSS评分低于对照组(P<0.05)。治疗后，两组脑卒中患者NSE浓度较治疗前降低而BDNF浓度较治疗前升高(P<0.05);且研究组脑卒中患者NSE浓度低于对照组而BDNF浓度高于对照组(P<0.05)。治疗后，两组脑卒中患者Hcy和hs-CRP浓度较治疗前降低(P<0.05);且研究组脑卒中患者Hcy和hs-CRP浓度低于对照组(P<0.05)。研...     

氯吡格雷抵抗影响因素的研究

联合应用氯吡格雷和阿司匹林是急性冠状动脉综合征和经皮冠状动脉介入(PCI)患者抗血小板治疗的基石,但再发缺血事件仍持续发生.研究发现临床患者对氯吡格雷的反应性存在变异,血小板聚集率测量平均21％的患者属于低反应(95％ CI:0.17～0.25)[1].这种低反应性即氯吡格雷抵抗( clopidogrel resistance,CR).若认识到引起这种低反应的不可纠正因素,寻找可以弥补这种低反应的可纠正因素,有助于确定有可能发生低反应的人群[2],从而制定个体化的抗血小板治疗策略、改善患者预后.本文拟从患者个体因素、疾病因素及处理对策等方面对CR的影响因素进行综述.     

2型糖尿病对急性ST段抬高型心肌梗死患者氯吡格雷抵抗的影响

目的 探讨2型糖尿病对急性ST段抬高型心肌梗死患者氯吡格雷抵抗的影响.方法 入选首都医科大学附属北京安贞医院就诊的急性ST段抬高型心肌梗死患者978例,分为2型糖尿病组（272例）和非2型糖尿病组（706例）,术前给予氯吡格雷,总量≥300 mg,将5μmol/L二磷酸腺苷诱导的血小板聚集率大于50％定义为氯吡格雷抵抗.观察2型糖尿病组和非2型糖尿病组氯吡格雷抵抗发生率及联合终点事件的差异.结果 2型糖尿病组氯吡格雷抵抗发生率明显高于非糖尿病组氯吡格雷抵抗发生率[（44.1％（120/272）比14.7％（104/706）,P=0.017],联合终点事件发生率也明显高于非2型糖尿病组[16.2％ （44/272）比7.4％（52/706）,P=0.012].Logistic回归分析显示,2型糖尿病是影响急性ST段抬高型心肌梗死患者氯吡格雷抵抗的独立预测因素[比值比为4.710,95％置信区间为1.380 ～ 7.551,P=0.028）.结论 2型糖尿病是影响急性ST段抬高型心肌梗死患者氯吡格雷抵抗的独立预测因素.     

急性冠状动脉综合征患者氯吡格雷治疗后血小板高反应性危险因素分析

目的探讨急性冠状动脉综合征(ACS)患者接受经皮冠状动脉介入(PCI)、氯吡格雷治疗后发生血小板高反应性(HPR)的危险因素及危险因素预测HPR的效力。方法 392例接受PCI治疗的ACS患者,术后予氯吡格雷75 mg·d-1维持剂量服用5 d后晨起空腹接受血栓弹力图(TEG)检查,根据对二磷酸腺苷(ADP)诱导的血小板抑制率的测定结果分为氯吡格雷治疗后HPR组(n=53)和氯吡格雷治疗后血小板低反应性(LPR)组(n=339),比较两组患者一般临床资料、实验室指标、TEG参数和手术资料,多因素logistic回归分析HPR的影响因素。利用受试者工作曲线(ROC curve)检验独立危险因素MAADP预测HPR的效力。结果 392例ACS患者HPR发生率为13.5%。两组患者的糖尿病、血红蛋白、MAADP、阿司匹林抑制率、阿司匹林抵抗、多支血管病变(MVD)的差异有显著意义(P<0.05或P<0.01)。条件logistic回归分析结果示HPR的独立危险因素有糖尿病(OR=2.670,95%CI:1.190~5.986,P=0.017)、MAADP(OR=1.189,95%CI=1.136~1.245,P<0.001)、糖尿病和MVD的交互作用(OR=6.975,95%CI:2.618~18.580,P<0.001)。利用MAADP预测HPR的ROC曲线下面积(AUC)为0.939(95%CI:0.914~0.964,P<0.001)。当MAADP取最佳临界值(cutpoint)47.65%时,诊断氯吡格雷抵抗的敏感性为92.45%,特异性为87.32%,阳性预测值为53.26%,阴性预测值为98.67%。结论糖尿病、MAADP和多支血管病变的交互作用为ACS患者HPR的独立危险因素,通过MAADP预测HPR的效力良好。     

缺血性脑卒中患者CYP2C19基因代谢型、联用药物与氯吡格雷抵抗关系的研究

目的 探讨CYP2C19基因代谢型、联用药物与氯吡格雷抵抗的关系.方法 选择缺血性脑卒中患者102例,连续口服氯吡格雷75 mg/d,共7d.检测患者CYP2C19各基因型及血小板聚集率,以1年内发生缺血性脑卒中复发终点事件为观察指标.结果 CYP2C19基因弱代谢型15例,中间代谢型39例,强代谢型48例,氯吡格雷抵抗发生率在弱代谢型较中间代谢型高,中间代谢型较强代谢型发生率高,差异均有统计学意义(P＜0.05);氯吡格雷联用阿司匹林、他汀类药可明显减少卒中复发事件(P＜0.05).结论 采用基因分型法可预测缺血性脑卒中患者氯吡格雷疗效,指导临床个体化给药.氯吡格雷联用阿司匹林、他汀类药的应用效果较好.     

阿司匹林联合氯吡格雷对阿司匹林抵抗患者预防缺血性脑卒中的疗效评价

目的 观察阿司匹林联合氯吡格雷对阿司匹林抵抗患者预防缺血性脑卒中的临床疗效.方法 将80位患者随机分为两组,对照组每日服用阿司匹林100mg,连服14天;治疗组每日服用阿司匹林100mg加波立维(氯吡格雷)75mg,连服14天.结果 氯吡格雷可以有效地降低阿司匹林抵抗患者的血小板平均聚集率(P＜0.05),阿司匹林抵抗和半抵抗总发生率明显减少(P＜0.05),较少发生缺血性脑卒中(P＜0.05).结论 阿司匹林联合氯吡格雷治疗阿司匹林抵抗患者预防缺血性脑卒中有显著疗效,值得临床推广.     

CYP2C19基因多态性及患者主要临床资料与氯吡格雷药物抵抗的相关性研究

目的观察药物代谢酶系统中CYP2C19基因多态性及患者主要临床资料与服用氯吡格雷前后血小板聚集率变化(氯吡格雷药物抵抗)的相关性。方法入选拟行冠脉造影检查或支架植入治疗患者35例,根据围手术期应用氯吡格雷前后血小板聚集率变化,将患者分为氯吡格雷抵抗组和非抵抗组。检测CYP2C19基因型,并记录患者年龄、性别、烟酒史、高血压、糖尿病等主要临床资料,分析基因水平及临床水平各因素对血小板聚集及氯吡格雷药物抵抗的影响。结果检测出氯吡格雷抵抗的患者15例,CYP2C19慢代谢基因型患者4例,Logistic回归分析显示,CYP2C19基因型是氯吡格雷抵抗的危险因素(OR=1.236,95%CI:0.273~5.599,P=0.049)。结论 CYP2C19基因型在基因水平与氯吡格雷抵抗相关,临床水平资料未见明显相关性。     

CYP2C19、ABCB1和PON1基因多态性与氯吡格雷抑制血小板聚集作用的相关性研究

目的:探讨CYP2C19、ABCB1和PON1基因多态性与氯吡格雷抑制血小板聚集作用的相关性。方法:纳入诊断为急性缺血性脑卒中或接受经皮冠状动脉介入术(PCI)后服用氯吡格雷和阿司匹林治疗的患者59例,测定CYP2C19(rs4244285、rs4986893)、ABCB1(rs1045642)和PON1(rs662)基因型及血栓弹力图(TEG),并对患者进行1年的随访,记录临床终点事件。应用单因素和多因素回归,分析患者CYP2C19、ABCB1、PON1基因型、一般情况及临床因素对氯吡格雷抑制血小板聚集作用的影响,比较不同基因型患者的氯吡格雷疗效。结果:59例患者中氯吡格雷治疗相关的血小板高反应性(HTPR)的发生率为8.5%。CYP2C19快代谢型、中间代谢型和慢代谢型患者血小板抑制率分别为(86.0±10.1)%、(78.4±17.3)%和(66.4±23.0)%,快代谢型和慢代谢型之间血小板抑制率差异有显著性(P=0.047),ABCB1和PON1各基因型之间血小板抑制率的差异无显著性(P>0.05),全变量多因素logistic回归分析未发现CYP2C19、ABCB1、PON1基因型与HTPR相关(P=0.681)。随访1年中,CYP2C19快代谢型、中间代谢型、慢代谢型患者的临床事件分别有2、3和3例;ABCB1携带TT、TC、CC等位基因患者的临床事件分别有1,3和4例;PON1携带AA、AG、GG等位基因患者的临床事件分别有4,2和2例,各基因型之间患者临床终点事件差异无显著性(P>0.05)。结论:根据CYP2C19、ABCB1和PON1基因多态性尚不能预测服用氯吡格雷后的临床疗效。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.