重组人尿激酶的一般药理学研究

试验结果显示：尿激酶原（prouk)22．5万IU／kg、45．0万IU／kg和90．0万IU／kg3个组、赋形剂组和生理盐水组动物尾静脉注射给药,对小鼠一般行为活动表现和自发活动次数均无明显影响。prouk22．5万IU／kg、45．0万IU／kg和90．0万IU／kg三个组、赋形剂组和生理盐水组动物尾静脉注射给药,对大鼠一般行为活动表现均无明显影响,均能在旋转棒上协调平衡运动。此外,给药后20min,三个剂量组大鼠凝血时间虽有延长,但与生理盐水组或赋形剂组比较无显著性差异（P＞0．05）。prouk11．25万IU/kg、22．50万IU／kg、45．00万IU／kg三组静脉滴注给药,麻醉犬的ECG、HR、呼吸均无明显改变,与赋形剂组比较性差异。但prouk高剂量组动物的SAP、DAP、MAP在给药10－15min时短暂下降,这些反应在给药30min后均恢复正常。结果表明,prouk在受度剂量范围内对小鼠、大鼠精神神经活动和大鼠的凝血时间等均无明显影响,在45．00万IU/kg剂量时对麻醉犬有短暂的降低血压的作用。     

重组人尿激酶原急性毒性和长期毒性的研究

（1）重组人尿激酶原（prouk)单剂量分别经静脉和腹腔注射给药均未侧出小鼠的LD50,因此改作其最大给药量。结果表明,prouk单剂量经静脉及腹腔注射给药小鼠的最大给药量不低于9,000万IU／kg。（2） prouk 36.0万IU／kg、67．5万IU/kg、135．0万IU／kg和270．0万IU／kg四个剂量组连续给食蟹猴静脉滴注14d,每组4只猴,雌雄各半。实验过程中未见动物死亡。prouk36．0万IU/kg剂量组的食蟹猴给药期及恢复期,精神状态良好,一般行为活动正常,体重、分泌物、食欲及摄食量、心电图、血常规、血液生化、体表观察、尿常规和粪便隐血试验等基本正常,无明显变化。给药第14天和恢复期的脏器系数与病理组织学检查表明,动物的脏器、组织均未见由药物引起的异常病理改变,在生理盐水组或赋形剂组之间比较均无明显差异。而prouk67．5万IU／kg、135．0万IU／kg、270．0万IU／kg剂量组的食蟹猴出现皮下出血、充血、紫癜、尿、粪便隐血反应阳性、贫血以及心率加快等症状。给药期及恢复期,血清中检测出少量prouk抗体。结果表明,prouk的无毒安全剂量不低于36．0万IU／kg。     

海棠凝胶家兔单次皮肤给药毒性实验

通过家兔皮肤急性毒性实验,初步评价海棠凝胶对动物完整皮肤及破损皮肤所产生的毒性反应,为后续毒性试验和临床试验提供参考信息.采用最大给药量法,家兔16只,分为4组,即海棠凝胶完整皮肤组及破损皮肤组、赋形剂完整皮肤组及破损皮肤组,每组4只(♀、♂各半),给药前24h用电推剪推去背部两侧毛(约150cm2),破损皮肤制作:在脱毛区用9号针头划"#"字状,以划破表皮渗血为度,给药量均为2g/kg凝胶,给药组主药剂量为0.05g/kg,将供试品和赋形剂涂于脱毛区,用一层称样纸覆盖及兔固定衣固定,并用兔脖套将兔固定,24h后用生理盐水洗去受试物及赋形剂,仔细观察和记录动物出现的毒性反应情况,连续观察14d,并记录体重和进食量情况.结果表明:海棠凝胶完整皮肤组及破损皮肤组无动物死亡,动物体重、进食量与赋形剂组比较无显著性差异(P0.05),呼吸、自主活动等均未见中毒反应,动物处死后经对各组家兔系统剖检,对皮肤给药部位及其它组织脏器进行观察,未见明显病理性改变.结论:海棠凝胶单次皮肤给药2g/kg凝胶(主药剂量为0.05g/kg),家兔未见明显毒性反应.     

重组人尿激酶原药效学研究

利用人血浆及其产生的血栓凝块 ,在试管中模拟纤溶酶原激活剂在体内引起血栓溶解的过程及麻醉开胸犬电刺激冠脉左旋支引起的冠脉血栓形成模型评价重组人尿激酶原的溶栓活性 ,并与尿激酶进行比较 .InVitro实验结果表明 :2 4 0IU /mL是 prouk血纤维蛋白专一的最大浓度 ,低浓度的重组prouk比天然 prouk具有更高的溶栓能力 ,这可能与其非糖基化结构有关 .当重组prouk浓度小于 1μg/mL时 ,它在血浆中几乎不降解任何纤维蛋白原 .犬静脉给予重组人尿激酶原 9× 10 4 、4 .5× 10 4 、2 .2 5× 10 4 IU·kg- 1 对冠脉血栓产生显著的溶栓效果 ,栓塞冠脉血管很快出现再通 ,残存血栓较溶剂对照分别减少了 6 9.2 %、5 7.0 %、4 3.1% ;心肌梗死范围明显缩小 ;与等剂量尿激酶溶栓作用相似 .血浆优球蛋白溶解时间明显缩短 ;溶栓不伴有明显的血浆纤维蛋白原降解 ,而尿激酶溶栓的同时 ,纤维蛋白原明显降低 .除高剂量组个别动物外 ,对伤口出血量增加出血时间无明显影响 .而等剂量的尿激酶组伤口出血量及出血时间明显延长     

蝙蝠葛碱对肾上腺素所致药物性高血压大鼠的影响研究

目的研究蝙蝠葛碱对肾上腺素所致药物性高血压大鼠的影响.方法各组给药前均先给肝素钠500 U单位,模型组注射生理盐水(Saline)10 mL/kg、Ver组(0.98 mL/kg剂量给药组)、低剂量组(2 mg/kg)、中剂量组(4 mg/kg)、高剂量组(8 mg/kg)3个剂量给药组,在注射相应药物之后1~3 min之内,注射重酒石酸去甲肾上腺素注射液0.18 mL/kg.标记给药后各组大鼠的血压变化.结果Dau 2,4,8 mg/kg组和Ver组注射Dau及Ver后,血压下降明显,Dau 8 mg/kg组效果最显著平均动脉压均值降至12.9 kPa.Dau 4,8 mg/kg组和Ver组与Control组比较,统计学差异显著P<0.01.给予NA后,Dau 2,4 mg/kg组及Ver组血压均有所上升,Dau4 mg/kg组和Ver组升高幅度相似,Dau 8 mg/kg组血压上升幅度不足Control组一半(平均动脉压均值为17.6 kPa).且Dau 4,8 mg/kg组和Ver组与Control组比较,有显著差异P<0.01.结论提示Dau可以降低正常大鼠血压,不同浓度的Dau对NA引起的大鼠血压升高有明显的对抗作用.     

蒲地蓝消炎口服液的非临床安全性再评价

目的 对已上市蒲地蓝消炎口服液进行非临床安全性再评价，为临床应用提供参考依据。方法 单次给药毒性实验：40只SD大鼠随机分为阴性对照组和40.04、138.60、295.56 g生药/kg剂量组，单次灌胃给药后连续观察大鼠14 d内的体质量、摄食量等毒性变化。28 d给药毒性实验：将120只SD大鼠分为阴性对照组和10.01、32.03、64.06 g生药/kg剂量组，连续灌胃28 d,恢复期28 d,检测动物的体质量、摄食、眼科检查、临检、大体剖检及组织病理学等。结果 单次给药毒性实验：138.60 g生药/kg剂量组出现药后活动减少、俯卧等，295.56 g生药/kg剂量组7/10例动物死亡，单次给药的最大耐受量(MTD)为138.60 g生药/kg。28 d给药毒性实验：除32.03、64.06 g生药/kg组部分动物出现肝细胞肥大外，其余剂量组均未见与药物相关的异常变化，28 d给药最大未观察到损害作用剂量(NOAEL)为64.06 g生药/kg。结论 通过SD大鼠的单次给药毒性实验和连续28 d经口灌胃毒性实验，提示蒲地蓝消炎口服液在临床给药周期内安全、无毒。     

冰片对反式白藜芦醇药动学的影响研究

为了研究冰片对反式白藜芦醇(resveratrol,Res)药代动力学的影响,将雄性SD大鼠分为灌胃给药和尾静脉注射给药两大组,灌胃给药组和尾静脉注射给药组均包括反式白藜芦醇(30 mg/kg)单用组,反式白藜芦醇与低、中、高剂量冰片(50、100和200 mg/kg)合用组.大鼠给药后不同时间点Res的血药浓度用高效液相色谱法测定,并用DAS3.0软件处理计算Res药动学参数.结果表明,不管是灌胃给药,还是静脉注射给药,冰片对反式白藜芦醇大鼠体内药动学均有明显影响.尾静脉注射给药中,单用Res对照组的药-时曲线下面积AUC0~∞为(127.04±29.84)mg/(L·min),血浆药物总清除率CLz为(0.088±0.029)L/(min·kg).低、中剂量冰片对Res的药代动力学无显著影响,高剂量冰片使血浆中Res的AUC(0~∞)增大了73.6%,CLz降低了42.1%,且与对照组相比差异具有统计学意义(P0.05).表明高剂量冰片可促进Res的吸收,降低Res的体内清除.1     

青蒿浸膏对SD大鼠的亚慢性毒性

研究青蒿浸膏的亚慢性毒性反应及其靶器官.设3.0、 3.9、 5.1、 6.8 g/kg 4个给药剂量组和一个空白对照组,空白组为大豆油;经口给Sprague-Dawley大鼠灌服1次/d,连续给药28 d;分别于相应时间点对大鼠行为、组织病理学变化、血液生理生化指标等进行检测.结果表明,给药5 d后, 5.1和6.8 g/kg组雄性大鼠均出现听力减弱的现象. 3.9、5.1和6.8 g/kg组雄性大鼠白细胞和淋巴细胞数量均高于对照组; 3.0、 3.9、 5.1和6.8 g/kg组雄性大鼠红细胞少于对照组; 4个剂量组雌、雄大鼠血清肌酐水平均少于对照组. 5.1、 6.8 g/kg组雌、雄大鼠肝脏脏器系数均明显增大.解剖和病理学结果表明,高剂量组的肝脏、中央静脉周围结构和小肠的结构有病变.高剂量青蒿浸膏连续用药28 d对大鼠神经系统、血细胞和肝脏造成毒性损伤, 3.0 g/kg为安全剂量.     

阿霉素对昆明种小白鼠腹腔给药的半致死剂量研究

目的:研究阿霉素对小白鼠经腹腔给药途径的半致死剂量.方法:通过预实验得到近似的最大致死剂量(Dm)和最小致死剂量(Dn),在正式实验中,将70只小鼠随机分为7组,每组10只,雌雄各半.给药途径为腹腔注射,给药次数1次,给药剂量为对照组给生理盐水,其余六组的剂量分别是13.4 mg/kg、19.2 mg/kg、27.4 mg/kg、39.2 mg/kg、56 mg/kg、80 mg/kg.给药后观察时间为14 d,统计小鼠的死亡情况.结果:除对照组和最小剂量(13.4 mg/kg)外,其他剂量组在7 d内均有数量不等的动物死亡,并且死亡率随着阿霉素浓度的增加而递增.经Bliss软件计算,其LD50值为24.941 mg/kg,95%的可信限为21.241～29.271 mg/kg.     

精苓消瘤胶囊对Beagle犬的长期毒性研究

观察精苓消瘤胶囊长期给药对Beagle犬产生的毒性反应,确定无毒反应剂量,为临床安全用药的剂量设计提供参考资料.将Beagle犬分为对照组及精苓消瘤胶囊高、中、低(1.50、0.60、0.25g/kg)3个剂量组,每组6只,雌雄各半,每天灌胃给药,每周给药6 d,共给药180 d,并进行恢复期观察.心电图指标中,给药结束时0.60 g/kg组心率、1.50、0.60 g/kg组PR及0.25 g/kg组QRS间期与对照组比较均有降低.血液学检查,给药结束时1.50 g/kg组的WBC与对照组比较有升高.生化学检查,给药90 d时,1.50、0.25 g/kg组的TP与对照组比较有降低,0.60 g/kg组BUN升高,0.60、0.25g/kg组TG降低.给药结束时,1.50 g/kg组ALB降低.恢复期结束时上述指标统计学差异消失.尿常规检查,各组BLO、KET、PRO有一定的阳性结果.在本试验条件下,Beagle犬口服精苓消瘤胶囊180 d给药的未见明显毒性反应剂量为0.60 g/kg.     

Characterization of Ordovician carbonate reservoirs, southeastern Saskatchewan, Canada

The discovery of the prolific Ordovician Red River reservoirs in 1995 in southeastern Saskatchewan was the catalyst for extensive exploration activity which resulted in the discovery of more than 15 new Red River pools. The best yields of Red River production to date have been from dolomite reservoirs. Understanding the processes of dolomitization is, therefore, crucial for the prediction of the connectivity, spatial distribution and heterogeneity of dolomite reservoirs.The Red River reservoirs in the Midale area consist of 3～4 thin dolomitized zones, with a total thickness of about 20 m, which occur at the top of the Yeoman Formation. Two types of replacement dolomite were recognized in the Red River reservoir: dolomitized burrow infills and dolomitized host matrix. The spatial distribution of dolomite suggests that burrowing organisms played an important role in facilitating the fluid flow in the backfilled sediments. This resulted in penecontemporaneous dolomitization of burrow infills by normal seawater. The dolomite in the host matrix is interpreted as having occurred at shallow burial by evaporitic seawater during precipitation of Lake Almar anhydrite that immediately overlies the Yeoman Formation. However, the low δ18O values of dolomited burrow infills (-5.9‰～ -7.8‰, PDB) and matrix dolomites (-6.6‰～ -8.1‰, avg. -7.4‰ PDB) compared to the estimated values for the late Ordovician marine dolomite could be attributed to modification and alteration of dolomite at higher temperatures during deeper burial, which could also be responsible for its 87Sr/86Sr ratios (0.7084～0.7088) that are higher than suggested for the late Ordovician seawaters (0.7078～0.7080). The trace amounts of saddle dolomite cement in the Red River carbonates are probably related to "cannibalization" of earlier replacement dolomite during the chemical compaction.     

A computer generator for randomly layered structures

AcomputergeneratorforrandomlylayeredstructuresYUJia shun1,2,HEZhen hua2(1.TheInstituteofGeologicalandNuclearSciences,NewZealand;2.StateKeyLaboratoryofOilandGasReservoirGeologyandExploitation,ChengduUniversityofTechnology,China)Abstract:Analgorithmisintrod…     

An Index mechanism for multi-scale view in spatial databases

There are numerous geometric objects stored in the spatial databases. An importance function in a spatial database is that users can browse the geometric objects as a map efficiently. Thus the spatial database should display the geometric objects users concern about swiftly onto the display window. This process includes two operations:retrieve data from database and then draw them onto screen. Accordingly, to improve the efficiency, we should try to reduce time of both retrieving object and displaying them. The former can be achieved with the aid of spatial index such as R-tree, the latter require to simplify the objects. Simplification means that objects are shown with sufficient but not with unnecessary detail which depend on the scale of browse. So the major problem is how to retrieve data at different detail level efficiently. This paper introduces the implementation of a multi-scale index in the spatial database SISP (Spatial Information Shared Platform) which is generalized from R-tree. The difference between the generalization and the R-tree lies on two facets: One is that every node and geometric object in the generalization is assigned with a importance value which denote the importance of them, and every vertex in the objects are assigned with a importance value,too. The importance value can be use to decide which data should be retrieve from disk in a query. The other difference is that geometric objects in the generalization are divided into one or more sub-blocks, and vertexes are total ordered by their importance value. With the help of the generalized R-tree, one can easily retrieve data at different detail levels.Some experiments are performed on real-life data to evaluate the performance of solutions that separately use normal spatial index and multi-scale spatial index. The results show that the solution using multi-scale index in SISP is satisfying.     

海南岛地体及其毗邻陆缘晚中生代—新生代古地磁研究和构造演化

本文叙述了对海南岛及其毗邻大陆边缘白垩纪到第四纪地层岩石进行古地磁研究的全部工作过程。通过分析岩石中剩余磁矢量的磁偏角及磁倾角的变化,提出海南岛白垩纪以来经历的构造演化模式如下:早期伴随顺时针旋转而向南迁移,后期伴随逆时针转动并向北运移。联系该地区及邻区的地质、地球物理资料,对海南岛上述的构造地体运动提出以下认识:北部湾内早期有一拉张作用,主要是该作用使湾内地壳显著伸长减薄,形成北部湾盆地。从而导致了海南岛的早期构造运动,而海南岛后期的构造运动则主要是受南海海底扩张的影响。海南地体运动规律的阐明对于了解北部湾油气盆地的形成演化有重要的理论和实际意义。     

Exciton Seebeck in Molecular Systems

Various applications relevant to the exciton dynamics,such as the organic solar cell,the large-area organic light-emitting diodes and the thermoelectricity,are operating under temperature gradient.The potential abnormal behavior of the exicton dynamics driven by the temperature difference may affect the efficiency and performance of the corresponding devices.In the above situations,the exciton dynamics under temperature difference is mixed with     

Achieving Unusual States of Matter Under High Pressure

The elongation method,originally proposed by Imamura was further developed for many years in our group.As a method towards O(N)with high efficiency and high accuracy for any dimensional systems.This treatment designed for one-dimensional(ID)polymers is now available for three-dimensional(3D)systems,but geometry optimization is now possible only for 1D-systems.As an approach toward post-Hartree-Fock,it was also extended to     

《Chinese Science Bulletin》SUBJECT INDEX TO VOLUME 59(2014)

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An on-line scaling method for improving scalability of a database cluster

The explosive growth of the Internet and database applications has driven database to be more scalable and available, and able to support on-line scaling without interrupting service. To support more client's queries without downtime and degrading the response time, more nodes have to be scaled up while the database is running. This paper presents the overview of scalable and available database that satisfies the above characteristics. And we propose a novel on-line scaling method. Our method improves the existing on-line scaling method for fast response time and higher throughputs. Our proposed method reduces unnecessary network use, i.e. , we decrease the number of data copy by reusing the backup data. Also, our on-line scaling operation can be processed parallel by selecting adequate nodes as new node. Our performance study shows that our method results in significant reduction in data copy time.     

An improved R-tree based on childnode''s probability

R-Tree is a good structure for spatial searching. But in this indexing structure,either the sequence of nodes in the same level or sequence of traveling these nodes when queries are made is random. Since the possibility that the object appears in different MBR which have the same parents node is different, if we make the subnode who has the most possibility be traveled first, the time cost will be decreased in most of the cases. In some case, the possibility of a point belong to a rectangle will shows direct proportion with the size of the rectangle. But this conclusion is based on an assumption that the objects are symmetrically distributing in the area and this assumption is not always coming into existence. Now we found a more direct parameter to scale the possibility and made a little change on the structure of R-tree, to increase the possibility of founding the satisfying answer in the front sub trees. We names this structure probability based arranged R-tree (PBAR-tree).     

Integrating GIS Web services based on mediating architecture

The geographic information service is enabled by the advancements in general Web service technology and the focused efforts of the OGC in defining XML-based Web GIS service. Based on these models, this paper addresses the issue of services chaining,the process of combining or pipelining results from several interoperable GIS Web Services to create a customized solution. This paper presents a mediated chaining architecture in which a specific service takes responsibility for performing the process that describes a service chain. We designed the Spatial Information Process Language (SIPL) for dynamic modeling and describing the service chain, also a prototype of the Spatial Information Process Execution Engine (SIPEE) is implemented for executing processes written in SIPL. Discussion of measures to improve the functionality and performance of such system will be included.