甘露醇对动物静脉血栓形成及凝血时间的影响

目的:研究甘露醇对动物实验性血栓形成及凝血时间的影响;方法:给大白鼠颈外静脉、家兔耳缘静脉及小白鼠尾静脉注射10%～20%甘露醇100～200mg·kg-1,观察其对动物体外血栓形成及凝血时间的影响.结果:20%甘露醇200 mg·kg-1对大白鼠、家兔体外血栓形成有促进的作用,促进率分别为30.6%,31.5%;10%甘露醇对大白鼠和家兔体外血栓形成几乎无促进作用,与生理盐水比较差异无显著性(P＞0.05);10%～20%甘露醇100～200 mg·kg-1对小白鼠体外凝血时间具有缩短作用,与生理盐水比较差异有显著性(P＜0.05).结论:20%甘露醇200 mg·kg-1对大白鼠和家兔体外血栓形成有弱的促进作用,不同浓度甘露醇对小白鼠凝血时间均有缩短,     

脑得生口服微乳制剂与片剂在大鼠体内药动学比较

目的:比较脑得生口服微乳制剂与片剂中有效成分的药动学特征,为脑得生口服微乳剂型设计及合理性评价提供依据。方法:选用清洁SD大鼠,随机分为实验组和对照组,分别灌胃给予脑得生口服微乳制剂1.8 mL·kg^-1·d^-1和脑得生片剂1.08 g·kg^-1·d^-1,收集处理大鼠血液样本,采用HPLC法于不同时间点(5,10,20,30,45 min,1,1.5,2,4,6,8,12 h)测定血浆中脑得生主要活性成分羟基红花黄色素A(HSYA)、人参皂苷Rg1、葛根素(Puer)、川芎嗪(TMP)的浓度。采用非房室模型计算主要药动学参数,并利用SPSS13.0统计软件进行统计学分析。结果:相比脑得生片剂,口服微乳制剂中HSYA、Rg1、Puer、TMP在大鼠体内的血药浓度-时间曲线下面积(AUC_0-12、AUC_0-∞)和峰浓度(C_max)均明显增加(P<0.05),Puer的体内消除半衰期(t_1/2)也明显延长(P<0.05)。结论:脑得生口服微乳制剂可有效增加有效成分HSYA、Rg1、Puer、TMP的吸收和生物利用度,是对中药制剂剂型改造的一次成功的探索。     

反相高效液相色谱法测定脑得生胶囊中葛根素的含量

目的采用高效液相色谱法测定脑得生胶囊中葛根素的含量,以控制该制剂的质量.方法以C18化学键合硅胶柱分离葛根素,以甲醇-乙腈-水(9∶8∶90)为流动相,UV检测波长250nm.结果方法的平均加样回收率为98.8%,RSD=1.08%(n=5).葛根素在0.25～2.5μg范围内,进样量与吸收面积值呈良好的线性关系.结论本法测定脑得生胶囊中葛根素的含量,结果准确,重复性好.     

反相高效液相色谱法测定脑得生胶囊中葛根素的含量

目的　采用高效液相色谱法测定脑得生胶囊中葛根素的含量 ,以控制该制剂的质量。方法　以C1 8化学键合硅胶柱分离葛根素 ,以甲醇 -乙腈 -水 (9∶8∶90 )为流动相 ,UV检测波长 2 5 0nm。结果　方法的平均加样回收率为 98.8% ,RSD =1 0 8%(n =5 )。葛根素在 0 .2 5～ 2 .5 μg范围内 ,进样量与吸收面积值呈良好的线性关系。 结论　本法测定脑得生胶囊中葛根素的含量 ,结果准确 ,重复性好     

灵芝多糖的药效学研究Ⅰ.抗恶性肿瘤、抗血栓和抗凝血作用

本文用 1.灵芝子实体经水提、乙醇沉制得灵芝多糖 (GL PS)精品 ,用苯酚 -硫酸法测其百分含量。 2 .应用小鼠移植性恶性肿瘤瘤株 (S1 80 、U1 4 、EAC) ,观察 GL PS对荷瘤小鼠肿瘤生长的影响。 3.观察 GL PS对小鼠全血凝血时间及出血时间和大鼠血栓及血液凝固系统的影响。实验结果 1.用本方法提取 GL PS得率为 0 .5 89± 0 .135 %。2 .GL PS 40 m g/ (kg· d) .ig× 17d对小鼠肉瘤 (S- 180 )和宫颈癌 (U - 14)的平均抑瘤率分别为 43%和 5 1% ,而对艾氏腹水癌 (EAC)小鼠生命没有明显延长作用 (P>0 .0 5 )。 3.GL PS 2 0 m g/ (kg· d) .ig× 10 d或 2 0～ 40 mg· kg- 1 .iv均能明显延长小鼠的凝血时间和出血时间 (P<0 .0 1)。GL PS 40 m g/ (kg· d) .ig× 10 d能明显抑制大鼠的血栓形成 (P<0 .0 1) ,降低纤维蛋白原的含量 (P<0 .0 1) ,同时能明显延长部分凝血活酶时间 (KPTT) (P<0 .0 1)。说明 GL PS具有抗肿瘤、抗血栓和抗凝血的作用     

延胡索乙素抗大鼠血栓作用研究

目的:研究延胡索乙素对大鼠体内动静脉血栓形成和凝血指标的影响.方法:分别采用大鼠下腔静脉结扎、动静脉旁路和FeCl3动脉血栓模型,将SD大鼠随机分为空白对照组、阿司匹林组(40 mg· kg-1)、延胡索乙素组(20、40、80 mg· kg-1),各组动物连续灌胃7d,末次给药2h后建立各血栓模型,测定延胡索乙素对血栓形成的影响;并测定了各组大鼠给药后2h血浆PT和APTT.结果:延胡索乙素各剂量组能抑制大鼠静脉血栓形成(高剂量抑制率达54.2％),有效的降低FeCl3刺激动脉血栓和动静脉旁路血栓重量(高剂量时抑制率分别为32.8％和43.7％);延长大鼠血浆活化部分凝血酶时间(APTT)、凝血酶原时间(PT).结论:延胡索乙素能抑制大鼠静脉血栓、动脉血栓和动静脉旁路血栓的形成.     

丹参注射液生物活性限度测定方法适用性研究

目的探讨丹参注射液生物活性测定方法的适用性。方法采用小鼠体内血栓形成试验、兔体外血小板聚集试验和兔体外血浆活化部分凝血活酶时间（APTT）试验,观察3个厂家,每厂各1批丹参注射液的药理作用,作为生物活性测定方法和限值确定依据。结果3批样品可明显增加血栓形成试验偏瘫恢复数,明显延长急性脑缺血试验小鼠存活时间;3批样品对二磷酸腺苷（ADP）诱导兔体外血小板聚集率有明显抑制作用,可明显延长兔血浆的活化部分凝血活酶时间（APTT）,体内体外的结果作用趋势相近。结论小鼠体内血栓形成试验、兔体外血小板聚集试验和兔体外血浆活化部分凝血活酶时间（APTT）试验均可作为丹参注射液生物活性测定方法,建议限值剂量为5g生药·kg-1。选用其中1种方法测定结果阳性即可判断为合格。若结果为阴性,需加做另2种试验,结果必须均为阳性后才能判断为合格。采用生物活性测定方法可对产品进行质量内部控制,积累数据,为制定正式标准提供依据。     

藏药脑血康对血瘀大鼠血流变及大鼠体外血栓形成的影响

目的观察脑血康对急性"血瘀"模型大鼠血流变的改善作用以及对大鼠体外血栓形成和影响。方法采用肾上腺素和冰水浴制造大鼠"血瘀"模型,测定血液流变学各项指标,同时还采用实验性动—静脉血栓形成法观察其体外抗血栓形成作用。结果脑血康0.5 g.kg-1组能明显降低高、中、低切变率下的全血黏度(ηb)和全血还原黏度(ηr)、红细胞压积(HCT)以及红细胞聚集指数(AI),而对血浆黏度(ηp)未见明显影响;脑血康还可明显抑制大鼠实验性体外血栓形成,但对出血时间、凝血酶原时间、凝血酶时间、纤维蛋白原无影响。结论提示脑血康可降低"血瘀"大鼠血液黏稠度,并能明显抑制体外血栓的形成,具有一定的活血化瘀和抗血栓形成作用。     

脑安胶囊与阿司匹林抗血栓作用的比较

脑安胶囊(简称脑安)是由川芎、当归、红花、人参皂苷、冰片等组成的复方中药制剂,具有活血化瘀、益气通络的作用,主要应用于中风的治疗.我们比较了脑安和阿司匹林的抗血栓作用,为脑安的临床应用提供依据.1材料与方法1.1药品和试剂脑安(吉林辽源亚东制药厂,批号910508)内容物以2%羧甲基纤维素钠溶液配制成1%,3%和10%的药液;阿司匹林(中国医药公司上海市公司,批号920210);戊巴比妥钠(Serva公司,批号911008).5-腺苷二酸单钠盐(ADPNa,中科院上海生物化学研究所上海东风生化技术公司,批号910518).1.2动物Wistar(?)大白鼠,体重为(284±14)g,昆明种(?)小白鼠体重(23～25)g,均由中国科学院上海实验动物中心提供.1.3方法1.3.1抗大白鼠实验性血栓形成试验大鼠实验性血栓形成模型参照文献1的方法,用3%戊巴比妥钠45mg/kg ip麻醉,分离右颈总动脉及左颈外静脉.取3段聚乙烯塑料管,其中2段内径为1.5mm,长约为10cm,中段内径为2mm,长约为8.5cm.在3段聚乙烯管的中段放入一根长约6.5cm的4号手术     

RP-HPLC梯度洗脱测定脑得生分散片中人参皂苷Rb1、Rg1和三七皂苷R1的含量

目的 建立RP-HPLC同时测定人参皂苷Rb1、Rg1和三七皂苷R1的含量.方法 Thermo HYPERSIL ODS柱,乙腈-水梯度洗脱(0～12 min,乙腈19%;12～50 min,乙腈19%→40%),流速:1.0 ml·min-1;检测波长:203 nm.结果 进样量分别在0.75～15.0 μg、0.75～15.0 μg、0.15～3.0 μg范围内线性关系良好:平均加样回收率分别为99.30%、99.41%、98.82%,RSD分别为0.73%、0.68%、0.77%.结论 本方法简单易行,定量准确,重复性好,可用于脑得生分散片的含量测定.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

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.