D-二聚体及白细胞对孕妇Pre-DIC的预测价值

目的:观察D-二聚体(D-D)与白细胞(WBC)对孕妇弥散性血管内凝血(DIC)前状态(Pre-DIC)的预测价值。方法:选择57例妊娠并发生DIC的患者为妊娠DIC组,另选健康体检妇女30例为正常对照组,正常妊娠妇女30例,为正常妊娠组。采用美国ACLAd-vance全自动血细胞凝集仪检测凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)及凝血酶时间(TT)。D-D检测采用免疫比浊法;血浆鱼精蛋白副凝固试验(3P)、血小板计数(PLT)、白细胞(WBC)按常规方法。纤维蛋白原(Fib)、AT-Ⅲ采用酶联免疫吸附法(ELISA)测定。分析三组PT,TT,APTT,Fib,PLT,AT-Ⅲ,D-D,WBC,3P阳性率的差异,同期观察妊娠DIC组中不同诱因:胎盘早剥、羊水栓塞、死胎引产、先兆子痫、子宫破裂及难治性宫缩乏力患者PT,TT,APTT,Fib,PLT,AT-Ⅲ,D-D,WBC检测的差异,并通过图示分析找到D-D,WBC对Pre-DIC的预测范围值。结果:三组PT,TT,APTT,PLT,AT-Ⅲ,D-D,WBC比较,差异有统计学意义(P<0.01),PT,TT,APTT,D-D,WBC组间两两比较差异有统计学意义(P<0.05,P<0.01)。妊娠DIC组各种诱因的凝血因子PT,TT,APTT,Fib,PLT,AT-Ⅲ比较,差异均有统计学意义(P<0.01),各种诱因的PLT,AT-Ⅲ两两比较,PLT除B-D、B-C无差异外,AT-Ⅲ除C-D无差异外,其余均有统计学意义(P<0.01,P<0.05)。孕妇PreDIC的预测指标D-D>2 mg/L且<2.4 mg/L,WBC≥14×109/L。结论:妊娠妇女血D-D含量、WBC升高到一定值,结合起来拟可作为妊娠Pre-DIC的判断指标。     

肾病综合征患者常用凝血-纤溶项目的观察

目的通过测定肾病综合征患者常用凝血-纤溶项目,探讨其在肾病综合征中的临床意义。方法检测20例正常人和30例肾病综合征患者的血小板记数(PLT)、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白原(Fgb)、凝血因子Ⅺ、Ⅹ、Ⅸ、Ⅷ的活性和D二聚体(D-D)、抗凝血酶Ⅲ(AT-Ⅲ)、组织型纤溶酶原激活剂(t-PA)。结果Fgb、PLT、D-D增多,TT延长;Ⅹ、Ⅺ、Ⅷ因子的活性增强与正常对照相比有显著性差异(P<0.01);APTT时间缩短,AT-Ⅲ、t-PA减少,与正常对照相比有显著性差异(P<0.01);PT、Ⅸ与正常对照相比没有统计学意义(P>0.05)。结论肾病综合征患者存在凝血活性亢进,纤溶活性减弱,测定凝血-纤溶系统的项目,对肾病综合征易出现高凝状态形成血栓有着重要的临床意义。     

妊娠高血压综合征患者凝血功能和血小板活化标志物的检测和临床意义

目的探讨妊娠高血压综合征患者凝血功能和血小板活化标志物的改变及其临床意义。方法采用全自动血凝仪和流式细胞仪,检测健康非妊娠妇女60名、健康晚期妊娠60名和妊娠高血压综合征患者58例的凝血酶原时间(PT)、活化部分凝血酶原时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)、D-二聚体(D-dimer)、抗凝血酶-Ⅲ(AT-Ⅲ)、CD62p和血小板激活复合物(PAC)-1。全自动血凝仪采用凝固法检测PT、APTT、TT、FIB,免疫比浊法检测D-dimer,发色底物法检测AT-Ⅲ。应用流式细胞术检测CD62p和PAC-1。结果与健康非孕组比较,健康晚孕组及妊娠高血压综合征患者各组PT、APTT明显缩短、AT-Ⅲ明显降低、FIB和D-dimer明显升高,CD62和PAC-1表达明显增加,差异均具有统计学意义(P<0.05或P<0.01);与健康晚期妊娠组比较,妊娠期高血压组、轻度子痫前期组和重度子痫前期组PT、APTT明显缩短、AT-Ⅲ明显降低、FIB和D-dimer明显升高,CD62和PAC-1表达明显增加,差异亦具有统计学意义(P<0.05,P<0.01)。妊娠高血压综合征随病情加重,FIB、AT-Ⅲ、D-dimer、CD62p和PAC-1有增高趋势。TT差异无统计学意义(P>0.05)。结论妊娠期凝血功能指标和血小板活化标志物检测对妊娠高血压综合征病情监测,早期防治具有一定意义。     

用夹心酶免疫试验检测抗凝血酶Ⅲ

抗凝血酶Ⅲ(AT-Ⅲ)是一种进行性血浆凝血酶抑制剂,它除了抑制凝血酶和因子 Xa外,还通过与各种蛋白形成酶-抑制剂复合物来抑制因子Ⅸ、Ⅺ、Ⅻ和纤溶酶。目前的一些 AT-Ⅲ检测方法,都是根据 AT-Ⅲ的凝固抑制性质或免疫学性质而设计的。     

活性炭逆转利伐沙班对凝血试验干扰的效果评价

目的 评价活性炭逆转利伐沙班对凝血试验干扰的效果。方法 取体检人群临床常规凝血项目检测后的枸橼酸钠抗凝血样本,每次方便抽取20例,重复24次,共纳入480例。将20例血浆样本混合配置成正常混合血浆（NPP）,取1 mL NPP为N1组;NPP经活性炭处理后为N2组;NPP加入不同质量浓度的利伐沙班为N3组：100 μg/L（N3A组）、200 μg/L（N3B组）、300 μg/L（N3C组）、400 μg/L（N3D组）,每个质量浓度重复6次;N3组经活性炭处理后为N4组。收集急诊科首次使用利伐沙班治疗的患者22例,首次服用利伐沙班前6 h和后6 h采集血样分别为S1组和S2组,S2组经活性炭处理后为S3组。液相色谱-联用串联质谱测定N3组和S2组的利伐沙班质量浓度。检测N1、N2、N3、N4组凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）及纤维蛋白原（FIB）水平,蛋白C（PC）、蛋白S（PS）、抗凝血酶Ⅲ（AT-Ⅲ）以及凝血因子FⅡ、FⅤ、FⅦ、FⅧ、FⅨ、FⅩ、FⅪ、FⅫ活性和N1、N2、N3、N4、S1、S2和S3组抗Xa因子（Anti-Xa）活性。结果 与N1组比较,N2组PT、APTT、INR、FIB、PC、PS、AT-Ⅲ、Anti-Xa、FⅡ、FⅤ、FⅦ、FⅧ、FⅨ、FⅩ、FⅪ、FⅫ活性差异无统计学意义;N3组PT、APTT延长,INR水平,PS、AT-Ⅲ和Anti-Xa活性升高,FⅡ、FⅤ、FⅦ、FⅧ、FⅨ、FⅩ、FⅪ、FⅫ活性降低（P<0.01）,PC活性及FIB水平差异无统计学意义;N4组APTT延长,PS、FⅤ、FⅧ、FⅪ、FⅫ活性降低（P<0.01）。与N3组比较,N4组PT、APTT缩短,INR水平,PS、AT-Ⅲ和Anti-Xa活性明显降低,FⅡ、FⅤ、FⅦ、FⅧ、FⅨ、FⅩ、FⅪ、FⅫ活性升高（P<0.01）,FIB水平和PC活性差异无统计学意义。与S1组比较,S2组Anti-Xa活性升高,APTT延长;S3组APTT延长（P<0.01）;与S2组比较,S3组Anti-Xa活性降低,APTT缩短。N3A、N3B、N3C和N3D组PT、INR、APTT、PS水平及Anti-Xa活性逐次升高,FⅤ、FⅦ、FⅧ、FⅨ、FⅪ活性逐次降低（P<0.01）;N3组、S2组利伐沙班质量浓度与Anti-Xa活性呈正相关（r_s分别为0.989、0.969,P<0.01）。结论 活性炭能有效去除血浆中的利伐沙班,可以逆转由利伐沙班引起的异常凝血指标。     

香椿子正丁醇提取物抗凝血作用及其机制

目的:研究香椿子正丁醇提取物的抗凝血作用,并阐明其抗凝血作用的机制。方法:采用凝固法检测急性高凝模型大鼠血浆复钙时间(RT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT);Clauss凝固法检测纤维蛋白原(FIB)含量、发色底物法检测蛋白C(PC)活性、抗凝血酶Ⅲ(ATⅢ)活性。结果:香椿子正丁醇提取物中、高剂量组(10,20mg.kg-1)均能显著延长急性高凝模型大鼠RT、APTT(P<0.05);香椿子低、中、高剂量组均显著延长大鼠PT、TT(P<0.05),并且呈一定的剂量依赖关系。香椿子正丁醇提取物对大鼠血浆FIB含量、PC活性无明显影响,其中、高剂量组(10,20mg.kg-1)对大鼠血浆ATⅢ活性具有明显升高作用(P<0.05),且呈一定的剂量依赖关系。结论:香椿子正丁醇提取物具有抗凝血作用,其作用机制可能与提高血浆中ATⅢ活性有关。     

蒲黄煎液的抗大鼠实验性血栓作用

目的研究蒲黄对大鼠血栓形成的影响。方法分别采用大鼠动静脉吻合血栓形成模型和电刺激损伤颈总动脉血栓模型实验方法,将SD大鼠随机分为空白对照组、阿司匹林阳性对照组(0.3 g/kg)、蒲黄煎液高剂量组(8 g/kg)、中剂量组(4 g/kg)、低剂量组(2 g/kg),各组动物连续灌胃给药7 d,末次给药后1 h建立模型,测定各组动物血栓湿重及血栓栓塞率;测定血浆凝血酶原时间(PT)、活化部分凝血酶时间(APTT)及凝血酶时间(TT)。结果蒲黄能抑制动静脉吻合血栓的形成,使血栓湿重降低,血栓抑制率达15%~43%;同时蒲黄降低了大鼠电刺激动脉血栓栓塞率,使大鼠APTT、PT、TT明显延长,且具有剂量依赖关系。结论蒲黄能够对抗在体实验性血栓的形成,其抗血栓机制可能与APTT、PT、TT指标的改变有关。     

凝血功能及纤溶指标检测在妊娠高血压综合征诊断中的应用价值

目的：探讨凝血功能及纤溶指标检测在妊娠高血压综合征诊断中的应用价值。方法：选取某院收治的妊娠高血压综合征患者78例作为观察组,并依据不同妊娠结局将观察组分为妊娠期高血压(32例)、轻度子痫前期(24例)、重度子痫前期(22例)3个亚组,另选取同期收治的78例健康孕妇作为对照组。比较2组受试者及观察组3个亚组间凝血功能指标[凝血酶原时间(PT)、凝血酶时间(TT)、活化部分凝血酶原时间(APTT)、抗凝血酶Ⅲ(AT-Ⅲ)]及纤溶指标[D-二聚体(D-D)、预测纤溶指数(EPL)、纤溶指标(LY30)],绘制ROC曲线分析PT、TT、APTT、AT-Ⅲ、D-D、EPL、LY30及联合检测诊断妊娠高血压综合征的临床价值。结果:观察组PT、TT、APTT、AT-Ⅲ[(9.56±1.13)s、(12.41±1.15)s、(25.69±2.13)s、(91.63±7.58)%]均小于对照组[(13.02±1.28)s、(16.18±1.25)s、(34.58±2.41)s、(105.89±10.12)%],观察组3亚组间重度子痫前期<轻度子痫前期<妊娠期高血压,差异均有统计学意义(P&...     

TY602-1的抗凝血作用研究

目的:探讨TY602-1的抗凝血作用及其作用机制。方法:采用离体FⅩa酶活性测定法、小鼠体内凝血酶原时间(PT)、活化部分凝血酶时间(APTT)和凝血酶时间(TT)的测定实验、大鼠动静脉旁路丝线上血栓形成实验、大鼠下腔静脉血栓模型实验,观察TY602-1的抗凝血药效。结果:TY602-1能抑制FⅩa活性;口服1.25,2.5,5和10 mg·kg-1剂量时明显延长小鼠PT和APTT,但对TT无明显影响;口服10 mg·kg-1剂量能明显抑制大鼠动静脉旁路血栓和下腔静脉血栓形成。结论:TY602-1是一种具有较强抗凝血作用的FⅩa抑制剂,可作为预防和治疗深度静脉血栓和肺动脉栓塞的药物使用。     

金卷升板胶囊对模型大鼠血小板减少的改善作用

目的 探讨金卷升板胶囊对模型大鼠血小板减少的改善作用。方法 将36只雄性SD大鼠随机分为空白对照组(A组，等体积生理盐水)，模型组(B组，等体积生理盐水)，咖啡酸组(C组，9 mg/kg)，以及金卷升板胶囊高、中、低剂量组(D₁组、D₂组、D₃组，1.00,0.50,0.25 g/kg)，各6只。腹腔注射环磷酰胺溶液(100 mg/kg)，每日1次，连续3 d，以复制血小板减少大鼠模型，同时A组大鼠腹腔注射等体积生理盐水。在建模开始后第5天，各组大鼠予相应药物或生理盐水灌胃，每日1次，连续14 d。检测血小板计数(PLT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(Fib)；采用酶联免疫吸附法检测白细胞介素10(IL-10)、肿瘤坏死因子-α(TNF-α)的水平；称定脾脏质量并计算脾脏系数；采用苏木素-伊红染色，并在显微镜下观察脾脏组织病理形态。结果 与A组比较，B组大鼠PLT显著减少，PT,APTT,TT均显著延长，Fib和TNF-α水平均显著升高，IL-10水平显著降低，...     

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.     

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.     

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.