糖尿病肾病不同时期的血栓前状态分子标志物水平

目的：了解2型糖尿病（DM）患血栓前状态的变化，以及此变化是否与糖尿病肾病（DN）有关，是否与DN的病变程度有关。方法：正常对照组（20例），2型糖尿病患共118例，按尿白蛋白排泄率（UAER）分为3组，尿白蛋白阴性组（DMI）伴微量白蛋白尿组（DM2），伴明显白蛋白尿组（DM3），分别测定血栓前状态分子标志物GMP－140，D－D，PAI，tPa,vWF水平。结果：所有DM患GMP－140，D－D，PAI均较正常对照组明显升高，提示DM患体内存在血栓前状态，其中GMP－140、D－D、，PAI在伴白蛋白尿的DM组明显高于不伴白蛋白尿的DM组，提示高凝及纤溶活性异常与DN的发生有关，GMP－140，D－D在明显白蛋白尿组又显高于微量白蛋白尿组，提示随DN病变程度的加重，血液高凝状态及纤溶系统紊乱更加明显，结论：2型糖尿病患体内存在血液高凝状态和纤溶系统紊乱，并且与DN的发生有关，与DN病变的严重程度有关。     

通心络胶囊联合阿司匹林肠溶片对不稳定性心绞痛患者血小板活性的影响

目的探讨通心络胶囊联合阿司匹林肠溶片对不稳定性心绞痛（UAP）患者血小板活性的影响。方法选取我科诊治92例UAP患者,随机分为：对照组,46例,予以ACS诊治指南治疗;研究组,46例,在对照组治疗基础上加用通心络胶囊与阿司匹林肠溶片,两组疗程均为2月。并选择健康体检人群46例作为健康组。应用流式细胞仪检测两组患者测血小板表面活性标记蛋白的CD41、CD62p、CD63水平。结果治疗后研究组的血小板活化指标CD41、CD62p、CD63较对照组相比较明显降低（P〈0.01）;而与健康组相比,研究组CD62p、CD63明显升高（P〈0.01）,但是CD41差异无统计学意义（P〉0.05）。结论通心络胶囊联合阿司匹林肠溶片对UAP患者血小板活性有明显抑制作用。     

奥扎格雷对急性脑梗死患者血浆高敏C反应蛋白、血小板CD62p、CD63的影响

目的探讨奥扎格雷对急性脑梗死患者血浆高敏C反应蛋白（hs-CRP）和血小板膜糖蛋白CD62p、CD63的影响。方法选择60例住院的急性脑梗死患者,随机分为对照组和治疗组。治疗组用奥扎格雷80mg加入5%葡萄糖或生理盐水250ml静脉滴注,2次/d,连用10d。对照组用血塞通400mg加入5%葡萄糖或生理盐水250ml静脉滴注,每日1次,连用10d。观察两组治疗前后患者血浆hs-CRP和血小板膜糖蛋白CD62p、CD63的变化。结果两组治疗10d后,患者血浆hs-CRP和血小板膜糖蛋白CD62p、CD63的测定值均较治疗前明显下降（P〈0.01或P〈0.05）,且治疗组比对照组下降更明显（P〈0.05）。结论奥扎格雷具有降低血浆hs-CRP水平和减少血小板CD62p、CD63的表达的作用,从而减轻炎症反应和降低血小板的活化,改善脑梗死部位缺血缺氧和缺损神经功能。     

丹参多酚酸盐对急性心肌梗死PCI术后患者血管内皮和血小板活化功能的影响

目的：观察丹参多酚酸盐对急性心肌梗死PCI术后血浆丙二醛（MDA）、一氧化氮（NO）、内皮素（ET-1）和血小板糖蛋白CD63、CD62p的影响,以进一步探讨丹参多酚酸盐在保护急性心肌梗死患者血管内皮细胞免受损伤和抑制血小板激活的作用。方法选取该院2011年2月-2012年8月因急性ST段抬高性心肌梗死入院患者320例,所有患者均行急诊PCI治疗。将320例患者随机分为常规治疗组（155例）和丹参多酚治疗组（165例）。常规治疗组予以阿司匹林、氯吡格雷及阿托伐他汀等药物口服。而丹参多酚治疗组除上述治疗外,予以注射用丹参多酚400 mg静点,此后一天一次,持续7 d。入院时及治疗7 d末取静脉血6 mL分离血浆和血小板,通过生物化学、ELASA、流式细胞仪等方法检测血浆MDA、NO、ET-1和血小板糖蛋白CD63、CD62p的变化。结果治疗7 d末,两组患者血浆MDA、ET-1水平均较入院前明显降低（P〈0.01）;血浆NO水平显著升高（P〈0.01）;血小板糖蛋白CD63、CD62p水平较入院前显著降低（P〈0.01）;而与常规治疗组比,治疗7 d末丹参多酚治疗组,血浆MDA、ET-1水平和血小板糖蛋白CD63、CD62p水平均明显降低（P〈0.05）。血浆NO水平明显升高（P〈0.05）。结论注射用丹参多酚能保护急性心肌梗死患者血管内皮细胞,抑制血小板活化,对急性心肌梗死的治疗起到积极的作用。     

原发性肝癌患者血清TGFβ1和IL-8水平与预后的关系

目的：探讨原发性肝癌（肝癌）患者血清转化生长因子β1（TGFβ1）、白细胞介素-8（IL-8）、T细胞亚群水平及其与预后关系。方法：应用ELISA、放射免疫法及流式细胞术检测24例肝癌患者（HCC组）血清TGFβ1、IL-8及T细胞亚群水平。并与25例健康献血者（NC组）和25例乙型肝炎肝硬化者（LC组）比较。结果：HCC组血清TGFβ1、IL-8水平较NC组和LC组明显升高，HCC组和LG组CD4^＋细胞和CD4^＋／CD8^＋比值较NC组明显降低，CD8^＋细胞明显升高；HGC组血清TGFβ1水平与CD4^＋细胞数量及与CD4^＋／CD8^＋比值呈负相关，与CD8^＋细胞呈正相关。血清TGFβ1、IL-8水平及CD4^＋／CD8^＋比值与肝癌分期有关。结论：观察血清TGFβ1、IL-8及T细胞亚群水平的改变有助于肝癌的诊断及对预后的评价。     

2型糖尿病患者血小板α-颗粒膜蛋白与肾脏病变的关系

目的　探讨 2型糖尿病患者血小板α 颗粒膜蛋白 (GMP 140 )含量变化与肾脏病变的关系。方法　测定 349例 2型糖尿病患者血小板GMP 140、纤维蛋白原 (Fg)、尿白蛋白 (Alb)、血和尿α1微球蛋白 (α1 MG) ,并与 5 0例健康者作对照 ;对 5 1例糖尿病肾病 (DN)患者在治疗糖尿病的同时 ,应用抗血小板活性药物。结果　无糖尿病肾病 (NDN)组血小板GMP 140含量高于正常对照组 ,但低于DN组 ,5 1例DN患者经过治疗后肾功能明显好转。结论　血小板GMP 140含量变化与 2型糖尿病肾病关系密切     

糖尿病伴血管病变时血管内皮功能、纤溶活性及血小板活化的变化

目的：观察DM患者无（A组）与有（B组）血管病变时的血管内皮功能、纤溶活性及血小板活化状态的变化。方法：vWF用免疫电泳法,TMT GMP－140用ELISA法,t-PA和PAI－1用发色底物显色法,PAgT比浊法。结果：（1）vWF:Ag、TM、PAI－1和GMP－1404项指标,DM及其两个亚组都高于对照组,B组高于A组。(2)t-PA,B组高于对照组和A组。（3）PAgT,仅见B组高于对照组,以上的差异均有显著性意义（P＜0．05或P＜0．01）。结论：（1）DM早期即有血管内皮细胞损伤,发生血管病变则增高更为显著。（2）DM凝血与纤溶调节处于较高水平,PAI－1相对升高,系诱发血栓形成的危险因素。（3）血浆GMP－140为反映血小板活化敏感的指标。     

脂必泰胶囊对心血管疾病患者血小板活化分子与 基质金属蛋白酶9的作用

［摘要］目的通过观察脂必泰胶囊对心血管疾病患者血小板活化分子和基质金属蛋白酶 9（MMP 9）的作用以评价其对心血管疾病患者的疗效。方法用脂必泰胶囊对79例心血管病患者进行治疗3个月，观察治疗前后患者外周血小板的膜糖蛋白CD62p、CD63、CD41、CD61的表达并用ELISA法测定患者血清MMP 9水平。结果79例心血管病患者中有53例患者的CD62p、CD63表达较治疗前显著降低（P＜0.01）。治疗有效率达67.1%；有41例患者的血清MMP 9浓度值较治疗前显著降低（P＜0.01）。治疗有效率达51.9%。结论脂必泰胶囊能降低心血管疾病患者外周血的血小板活化分子和MMP 9，从而改善和调节脂质代谢紊乱和降低动脉硬化程度。     

烧伤患者血小板微粒的变化及临床意义

目的：对烧伤患者血小板微粒的变化及临床意义进行分析探讨。方法选取烧伤患者60例,将烧伤患者分为感染组和休克期组,以及选取同一时期到我院体检的正常成人30例为对照组,将三种对象的血浆中血小板微粒水平进行对比研究。结果休克期组的血小板明显低于对照组,统计学上有意义（ P ＜0．05）。休克期组和感染组的凝血酶原时间、血清总胆红素则明显高于对照组,统计学上有意义（ P ＜0．05）。感染组r-谷氨酰转肽酶明显高于休克期组,统计学上有意义（ P ＜0．05）。且感染组CD41＋CD31＋血小板微粒的比例明显高于休克期组,统计学上有意义（ P ＜0．05）。休克期组和感染组CD41＋、CD41＋CD31、CD41＋CD61＋血小板微粒水平明显高于对照组,统计学上有意义（ P ＜0．05）。结论血小板微粒的变化与烧伤患者的病情变化密切相关。     

氯吡格雷对不稳定型心绞痛患者血浆炎症因子和血小板活化因子的影响

目的：探讨氯吡格雷对不稳定型心绞痛（ACS）患者血浆炎症因子和血小板活化因子的影响。方法i70例ACS患者随机分为两组,均按ACS治疗方案进行治疗,观察组在此基础上加用氯吡格雷75mg,po,qd,连用8周。观察两组患者治疗前后血浆炎症因子hs—CRP、TNF—α、IL-6水平和血小板活化因子CD62p、CD63水平的变化。结果：两组患者治疗前血浆hs—CRP、IL-6和TNF—α水平比较,差异无统计学意义（P〉0．05）。治疗8周后,两组患者血浆hs-CRP、IL-6和TNF—α水平均较治疗前明显下降（P〈0．05或0．01）,且观察组下降的幅度较对照组更明显（P〈0．05）。两组患者治疗前血浆血小板活化因子CD62p和CD63水平差异无统计学意义（P〉0．05）,治疗8周后,两组患者血浆CD62p和CD63水平均较治疗前明显下降（P〈0．05或0．01）,且观察组下降的幅度较对照组更明显（P〈0．05）。结论：氯吡格雷对ACS患者具有抗炎,抑制血小板活化作用,从而改善血管内斑块的炎症反应,减少血小板的黏附和聚集作用,在一定程度上增加动脉粥样斑块的稳定性、阻断和逆转冠状动脉粥样斑块作用。     

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.     

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.