二母颗粒对小鼠Lewis肺癌模型的肿瘤血管生成的影响

目的 观察二母颗粒对C57BL/6小鼠体内Lewis肺癌生长、转移以及血管生成的影响及其作用机制.方法 制备C57 BL/6小鼠Lewis肺癌模型,随机分为二母颗粒高、中、低(3、2、1g·kg-1生药)剂量组、环磷酰胺组、沙利度胺组、模型组.分别给予相应药物后,观察各组小鼠的肿瘤生长情况及肺转移发生率,采用免疫组化方法观察瘤内血管内皮细胞生长因子(VEGF)和微血管密度(MVD)的表达.结果 二母颗粒高、中、低剂量组连续ig给药14 d,对小鼠Lewis肺癌的抑瘤率分别为30.80％、10.63％、0.其中,二母颗粒高剂量组的瘤重、抑瘤率、VEGF及MVD的表达与模型组比较均有显著差异(P＜0.05).结论 二母颗粒具有抑制小鼠Lewis肺癌的作用,其作用机制可能与抑制瘤内VEGF和MVD的生成有关.     

威麦宁抑制小鼠Lewis肺癌移植瘤的生长及其血管生成的实验研究

目的:探讨威麦宁对小鼠Lewis肺癌移植瘤生长及其血管生成作用的影响。方法:建立小鼠Lewis肺癌移植瘤模型,用药后取瘤组织称重并计算抑瘤率;瘤组织切片HE染色,光镜下进行形态学观察;免疫组化法检测瘤组织血管内皮细胞CD34的表达情况并计数微血管密度(MVD)。结果:威麦宁浓度在100mg/kg.d、250mg/kg.d时,对小鼠Lewis肺癌的抑制率分别为19.14%和51.56%;对照组癌巢间微血管丰富,用药组瘤组织及其周围微血管均减少;用药组瘤组织内MVD明显低于NS组(P<0.01)。结论:威麦宁能减少肿瘤组织血管生成,从而抑制小鼠移植瘤的体内生长。     

福安泰-03对肿瘤血管生成的抑制作用

目的研究从赤魟组织中分离到的福安泰-03(Fuan-tai-03,FAT-03)对肿瘤血管生成的影响。方法鸡胚绒毛尿囊膜(CAM)法检测FAT-03对人低分化鼻咽癌细胞(CNE-2Z)诱导的CAM血管生成的影响;免疫组化法检查FAT-03对裸小鼠Lewis肺癌组织微血管密度(MVD)和血管生成因子表达的影响。结果FAT-03抑制CNE-2Z细胞诱导的CAM血管生成,当其用量为20、40、80、160μg/胚/d×5时,其抑制率分别为22.3%、34.3%、43.3%、46.2%。FAT-03降低小鼠Lewis肺癌组织的MVD,FAT-03组平均微血管数为9.1±1.5(对照组为18.2±3.2,P<0.05)。免疫组化检测结果显示,FAT-03明显下调小鼠Lewis肺癌组织血管内皮细胞生长因子(VEGF),碱性成纤维细胞因子(bFGF)和血小板衍生生长因子(PDGF)的表达。结论FAT-03有抗肿瘤血管生成作用,其作用与它的下调VEGF、bFGF和PDGF的表达密切相关。     

复方苦参注射液联合环磷酰胺对小鼠Lewis 肺癌抑瘤作用的实验研究

目的探讨复方苦参注射液联合环磷酰胺对Lewis肺癌小鼠移植瘤生长、转移及血管新生的抑制作用及相关机制。方法建立C57BL·6^-1小鼠Lewis肺癌移植瘤模型,随机分为对照组、复方苦参组、CTX组和联合治疗组,每组各10只小鼠,分别腹腔注射生理盐水、复方苦参注射液、环磷酰胺、联合复方苦参注射液和环磷酰胺,定期检测皮下肿瘤体积,接种后12d处死小鼠,检测比较两组小鼠瘤体质量和体积、肺转移瘤结节数,同时以免疫组化法检测小鼠肿瘤组织中微血管密度（MVP）以及VEGF水平。结果复方苦参注射液联合环磷酰胺可显著减少瘤体质量和体积,减轻肿瘤转移,下调VEGF表达,抑制血管生成,与对照组、复方苦参组和CTX组比较差异均有统计学意义（P〈0．05或0．01）。结论复方苦参注射液和CTX可协同拮抗肿瘤新生血管生成,抑制肿瘤组织生长与转移,效果优于两者单独使用。     

多西他赛抑制小鼠肺癌血管生成分析

目的探讨常用化疗药物多西他赛化疗抑制肿瘤血管生成的作用。方法选择Lewis肺癌细胞荷瘤小鼠50只,随机分成多西他赛不同剂量治疗3组、生理盐水组和对照组,观察4周后5组最终肿瘤体积、质量以及移植瘤血管生成抑制情况。结果多西他赛组小鼠皮下移植瘤质量与体积明显小于其他组,其微血管数（MVD）亦明显低于其他组。结论多西他赛能明显抑制小鼠肺癌血管生成。     

人参皂苷Rh2 对荷Lewis 肺癌小鼠抗肿瘤作用

目的观察人参皂苷Rh2（ginsenoside Rh2,G-Rh2）对荷Lewis肺癌小鼠抗肿瘤作用并探讨其作用机制。方法建立Lewis肺癌实体瘤模型,观察G-Rh2的抗肿瘤作用、观察肿瘤内血管密度（MVD）,以及免疫组化法观察瘤体血管内皮生长因子（VEGF）的表达。结果 0.3 mg·kg^-1、1.0 mg·kg^-1和3.0 mg·kg^-1G-Rh2组对Lewis肺癌小鼠实体瘤均有抑制作用（P〈0.05）;1.0 mg·kg^-1和3.0 mg·kg^-1 G-Rh2组MVD明显低于对照组（P〈0.05）;免疫组化结果显示,0.3 mg·kg^-1、1.0 mg·kg^-1和3.0 mg·kg^-1 G-Rh2组瘤组织内的VEGF蛋白表达阳性率均低予对照组（P〈0.05）。结论 G-Rh2可抑制Lewis肺癌生长及抑制肿瘤新生血管生成的作用,可能是通过降低VEGF表达来实现的。     

塞来昔布联合吉西他滨对Lewis肺癌皮下移植瘤的抑制作用

目的研究塞来昔布(CEL)与吉西他滨(GEM)联用对Lewis肺癌皮下移植瘤的抑制效应。方法 40只小鼠随机分为对照组(A组)、GEM组(B组)、CEL组(C组)和CEL/GEM联用组(D组),每组10只。A、B组给予普通饲料;C、D组自接种后第2天给予含CEL 1mg/g的饲料喂养。B、D组于肿瘤接种后第7天,给予GEM 100mg/kg溶液0.2ml腹腔注射;A、C组给予等量生理盐水。每周注射1次,连续3周。实验期间测量肿瘤长短径,并绘制肿瘤生长曲线,4周后处死,称量瘤重,计算抑瘤率;检测移植瘤组织血管内皮生长因子(VEGF)表达、微血管密度(MVD)和肿瘤细胞的凋亡。结果 B、C和D组抑瘤率分别为54.18%、49.52%和88.59%;D组移植瘤组织的VEGF表达及MVD低于A、B和C组(P<0.05),而凋亡指数高于A、B和C组(P<0.05)。结论 CEL和GEM均能抑制Lewis肺癌移植瘤的生长,两者联用通过抑制肿瘤微血管生成及诱导肿瘤细胞凋亡发挥协同抗肿瘤效应。     

弓形虫溶解抗原抗小鼠B16黑色素瘤血管生成的实验研究

目的 观察弓形虫溶解抗原(TLA)对小鼠B16黑色素瘤生长以及肿瘤血管生成的影响.方法 20只C57BL/6J小鼠皮下接种B16黑色素瘤细胞,建立荷瘤动物模型,从小鼠荷瘤的第7天开始,每隔2天实验组小鼠经腹腔注射TLA 0.1 ml,对照组小鼠注射同等剂量0.9%氯化钠注射溶液,荷瘤21 d后处死小鼠剥取肿瘤,测量肿瘤体积与重量,计算抑瘤率,免疫组化法检测肿瘤微血管密度(MVD)与血管内皮生长因子(VEGF)表达情况.结果 TLA显著抑制了小鼠体内黑色素瘤生长,实验组肿瘤体积与重量明显小于对照组(P＜0.05),抑瘤率为49.6%.实验组与对照组的MVD值分别为(44.4000±4.7888)、(31.9000±2.6012),两组相比较差异有统计学意义(P＜0.05).实验组肿瘤VEGF表达明显低于对照组(P＜0.05).结论 TLA能够抑制小鼠B16黑色素瘤生长,其抗瘤机制可能与抗血管生成有关.     

乙二酰二脱水卫矛醇对小鼠移植性肝癌H_(22)肿瘤生长和血管生成的抑制作用

目的:研究乙二酰二脱水卫矛醇(DADAG)在体内对肿瘤生长和血管生成的抑制作用及其机制。方法:采用小鼠H22模型观察DADAG对肿瘤生长的影响;免疫组化和W estern blot法分别检测DADAG对肿瘤组织中微血管密度(MVD)和血管内皮生长因子(VEGF)以及转录因子Sp1表达的影响。结果:DAD-AG(5和10 mg.kg-1.d-1)可以浓度依赖性地降低小鼠瘤重(抑制率分别为29.8%和60.2%)和MVD(抑制率分别为38.9%和66.7%),引起肿瘤组织坏死,降低VEGF及Sp1的表达量,但无明显肝、肾毒性。结论:DADAG可以抑制小鼠H22移植瘤的生长和血管生成,下调VEGF及Sp1的表达是其可能的作用机制之一。     

川芎嗪联合顺铂对Lewis小鼠肺腺癌移植瘤与血管生成的影响

目的研究川芎嗪联合顺铂对Lewis肺腺癌小鼠移植瘤生长及抑制血管生成的作用机制。方法培养Lewis小鼠肺腺癌细胞,建立移植瘤模型。按照体重将成功制备的荷瘤小鼠模型随机分成4组,每组15只:模型组、顺铂组、川芎嗪组、联合组。模型组:0.9% NaCl,顺铂组:2 mg·kg^-1,川芎嗪组:100mg·kg^-1,联合组:两种药物相加。均每次0.2 mL,干预2周。称量瘤重,计算抑瘤率;用免疫组化方法检测每组血管内皮生长因子(VEGF)、血管抑制蛋白(VASH-1)的表达。结果给药后,联合组、顺铂组、川芎嗪组的抑瘤率分别为54.81%,32.36%,18.36%,与模型组(抑瘤率为0)比较,差异均有统计学意义(均P<0.05)。联合组、顺铂组、川芎嗪、模型组的VEGF表达分别为20.37±2.02,28.07±4.29,26.43±4.69,62.14±6.78;这4组的VASH-1表达分别为9.04±1.01,10.10±1.61,11.53±1.96,12.94±1.10,3个给药组与模型组相比,差异均有统计学意义(均P<0.05)。Pearson相关性分析:VEGF与VASH-1成正相关(r=0.664,P<0.05)。结论川芎嗪联合顺铂协同抑制Lewis小鼠移植瘤生长,其作用机制可能为川芎嗪与顺铂可以直接作用癌细胞,同时降低VEGF与VASH-1表达,发挥抗血管生成作用。     

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.     

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.     

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.     

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.