Brucine对Heps荷瘤小鼠的抗肿瘤作用和毒性的研究

目的观察和评价B ruc ine对移植性肝癌Heps模型荷瘤小鼠的肿瘤抑制作用和生存时间的影响,同时考察B ru-c ine对其免疫系统、造血系统及肝、肾的毒性。方法用ICR♂小鼠接种肝癌Heps瘤株造成移植性肝癌Heps小鼠模型,以B ruc ine对荷瘤小鼠的抑瘤率和生命延长率代表B ruc ine的抗肿瘤活性;以小鼠的体重、免疫器官指数、血细胞指数和肝、肾指数为指标观察B ruc ine对小鼠的毒性及可能的作用机制。结果B ruc ine对移植性肝癌Heps荷瘤小鼠的抑瘤率分别为30.34%(1.61 mg.kg-1)、46.21%(3.23mg.kg-1)和42.07%(6.46 mg.kg-1)。3.23 mg.kg-1(1/20 LD50)是其最佳剂量。但对其生存时间无延长作用。毒性考察实验显示B ruc ine对肝癌Heps小鼠的造血、免疫系统以及肝、肾无明显的毒性。相反B ruc ine还能提高其免疫器官的重量和指数,提高肝癌Heps小鼠的白细胞和血小板数,并能降低小鼠因接种肝癌Heps瘤株而造成的AST、ALT和BUN异常升高。结论B ruc ine能有效抑制移植性肝癌模型荷瘤小鼠体内肿瘤生长,短期对动物的造血、免疫系统以及肝肾没有明显的毒性,相反还能刺激和促进造血系统和免疫系统的功能,恢复小鼠因接种肝癌Heps瘤株而造成的肝肾功能的损伤。通过深入研究B ruc ine有可能发展成为一种新型抗癌药。     

银杏叶聚戊烯醇联合60Co放疗Heps荷瘤鼠的药效研究

从银杏叶中分离聚戊烯醇有效部位，选择肝癌实体型(Heps)，以5，10和20mg/kg不同剂量的聚戊烯醇，分别联合^60Co放疗Heps荷瘤鼠，并与^60Co单独放疗Heps进行对比，分析抑瘤效果。结果：5，10和20mg/kg的聚戊烯醇，分别联合^60Co放疗Heps荷瘤鼠，对Heps的抑瘤率分别为67.33％，60.96％和57.69％，都明显高于^60Co单独放疗Heps的抑瘤率(54.58％)，尤其低剂量的聚戊烯醇联合^60Co放疗效果最好。结论：银杏叶聚戊烯醇联合^60Co放疗Heps荷瘤鼠，可明显提高^60Co单独放疗Heps的抑瘤效果。     

江苏地产白首乌C21甾体苷对荷瘤小鼠的免疫保护作用

目的：探讨白首乌C21甾体苷对肝癌实体型（Heps）小鼠的抗肿瘤作用和免疫保护机制。方法：建立小鼠Heps移植模型，进行抑瘤率计算，对肿瘤病理组织进行观察；计算小鼠的胸腺、脾脏指数；用腹腔巨噬细胞吞噬中性红及分泌NO反映整体免疫功能；MTT法检测T、B淋巴细胞增殖；双抗体夹心ABC-ELISA法检测脾淋巴细胞诱生IL-2及腹腔巨噬细胞诱生TNF—α. 结果：C21甾体苷三个剂量组的抑瘤率分别为34．79％、47．08％和50．23％，病理检查可见肿瘤组织中有片状坏死；各剂量组均可降低荷瘤后异常增高的脾指数，升高胸腺指数；增强巨噬细胞吞噬能力；明显增强T、B淋巴细胞增殖反应；使脾细胞分泌IL-2及腹腔巨噬细胞分泌．TNF-α量显著提高：结论：白首乌C21甾体苷可提高荷瘤小鼠特异性和非特异性细胞免疫功能，促进抗肿瘤细胞因子的分泌．     

海生素注射液抗肿瘤作用的实验研究

目的 :研究海生素的抗肿瘤效果。方法 :采用小鼠移植性实体瘤S180 、艾氏腹水瘤 (EAC)和肝癌实体瘤 (Heps)模型的抑瘤试验 ,尾静脉给予小鼠不同剂量的海生素 ,计算抑瘤率和荷瘤小鼠生命延长率。结果 :海生素在 4 90～ 10 0 0mg·kg- 1·d- 1剂量范围内对小鼠S180 和Heps的抑瘤率分别达到 4 1.10 %～ 4 9.0 8%和 36 .2 9%～ 4 9.19% ,对EAC小鼠的生命延长率为 2 2 .93%～ 6 9.98%。结论 :海生素对荷瘤小鼠具有明显的抑瘤作用 ,在有效治疗肿瘤的同时对小鼠体重无明显影响。     

聚酯型儿茶素的抗肿瘤及免疫调节作用

目的：研究聚酯型儿茶素（ＴＳ）对小鼠移植瘤的抑制作用及对荷瘤小鼠免疫功能的影响。方法：应用小鼠艾氏腹水癌实体型、小鼠Ｓ１８０肉瘤和肝癌Ｈ２２３种模型进行了ＴＳ的抗肿瘤作用研究;应用小鼠迟发型超敏反应模型、小鼠碳粒廓清试验及脾淋巴细胞增殖试验研究了 ＴＳ对荷Ｓ１８０小鼠免疫功能的影响。结果：４００、２００、５０ｍｇ／ｋｇ ＴＳ对小鼠艾氏腹水癌实体型瘤生长有明显抑制作用;常规灌胃给药对小鼠Ｓ１８０和肝癌Ｈ２２的生长无明显抑制作用,但预防给药则对小鼠Ｓ１８０和肝癌Ｈ２２的生长有明显抑制作用,各组抑瘤率均大于 ３０％。５０、１００、２００ｍｇ／ｋｇ ＴＳ可使荷瘤小鼠降低的迟发性超敏反应恢复正常;亦可使荷瘤小鼠碳粒廓清指数 Ｋ和吞噬指数α值显著提高;还可明显增强荷瘤小鼠脾Ｔ淋巴细胞增殖反应。结论：ＴＳ对小鼠移植瘤有明显抑制作用,同时可增强荷瘤小鼠降低的免疫功能。     

扇贝裙边糖胺聚糖抗肿瘤作用和对荷瘤小鼠免疫功能的影响

目的：研究扇贝裙边糖胺聚糖（SS-GAG）的抗癌作用及对荷瘤小鼠免疫功能的影响。方法：建立小鼠移植性S180实体瘤模型，观察SS-GAG的抑瘤率以及对荷瘤小鼠的体质量、肝质量、白细胞计数、脾指数、胸腺指数的影响，同时观察SS-GAG对荷瘤小鼠细胞免疫活性的影响。结果：SS-GAG可明显抑制S180实体瘤的生长，SS-GAG与环磷酰胺联用可使化疗药物的抗癌作用增强并能有效提升减少的白细胞；能显著增强荷瘤小鼠腹腔巨噬细胞的吞噬能力和杀伤活性，增强荷瘤小鼠脾淋巴细胞的转化增殖和NK细胞活性。结论：SS-GAG可显著抑制肿瘤生长，与环磷酰胺联用时有减毒增效作用；并能增强荷瘤小鼠的免疫功能。     

灵芝孢子多糖抗移植性肿瘤实验研究

目的研究灵芝孢子多糖的抗癌作用。方法采用小鼠抗移植性肿瘤实验方法。结果灵芝孢子多糖分别以150 mg.kg-13、00 mg.kg-1和600 mg.kg-1剂量连续12天灌胃给药,对小鼠移植性肝癌Heps的抑瘤率为53.77%~65.25%;连续8天灌胃给药,对小鼠移植性肉瘤S180的抑瘤率为50.39%~55.04%,皆呈良好的抑瘤作用。灵芝孢子多糖可分别提高Heps和S180荷瘤小鼠的脾指数和胸腺指数。结论灵芝孢子多糖有良好的抑瘤作用,并可增强Heps和S180荷瘤小鼠的非特异性免疫功能。     

海洋真菌多糖YCP对小鼠扶正减毒作用的研究

从海洋真菌YC中提取的真菌多糖YCP,选择9,3,1 mg/kg的不同剂量,分别联合60Co放疗和Cy化疗正常小鼠和Heps荷瘤鼠,观察药物对放、化疗的减毒作用。以荷瘤小鼠观察药物对小鼠的扶正作用。结果:YCP(9,3,1 mg/kg)剂量组可显著地对抗由大剂量Cy造成的正常小鼠外周血白细胞,骨髓有核细胞数和胸腺指数的下降(P<0.01,P<0.05)。YCP(9,3 mg/kg)剂量组可显著地抑制由大剂量Cy和60Co照射造成的Heps荷瘤小鼠外周血白细胞,骨髓有核细胞数和脾脏指数和胸腺指数的下降(P<0.01,P<0.05)。YCP(9,3 mg/kg)可显著提高S180荷瘤小鼠的吞噬指数k和血清半数溶血值(P<0.01,P<0.05)。结论YCP可明显对抗由60Co照射,大剂量化疗药Cy引起的正常和荷瘤小鼠的血液和骨髓抑制毒性。YCP可显著提高S180荷瘤小鼠免疫功能。     

马钱子碱及其脂质体对移植性肝癌Heps小鼠的抗肿瘤作用和毒性的比较

目的:比较马钱子碱(brucine,B)和马钱子碱脂质体(brucine liposome,BL)对移植性肝癌Heps小鼠的抗肿瘤作用和毒性。方法:ICR雄性小鼠接种肝癌Heps瘤株造成移植性肝癌Heps小鼠模型(简称Heps小鼠),测定B(1·61,3·23,6·46 mg·kg~(-1)·d~(-1),ip,8 d)和BL(以B计,1．61和3．23 mg·kg~(-1)·d~(-1),ip,8 d)对实体瘤小鼠的抑瘤率和腹水瘤小鼠的生命延长率;并比较各组实体瘤小鼠的体重、免疫器官(脾和胸腺)指数、血细胞指数(白细胞、红细胞、血小板和血红蛋白)和肝、肾功能指数(AST,ALT和BUN)。结果:低、中、高剂量的B(1．61,3．23,6．46 mg·kg~(-1)·d~(-1))对Heps实体瘤小鼠的抑瘤率分别为35．05%,43．70%,46．09%;同剂量的BL(1．61,3．23 mg·kg~(-1)·d~(-1))的抑瘤率分别为45．41%和58．19%。BL对Heps实体瘤小鼠的肿瘤抑制作用显著强于B,但B和BL对Heps腹水瘤小鼠生存时间均无延长作用。B和BL在1．61,3．23 mg·kg~(-1)·d~(-1)时对Heps实体瘤小鼠的造血、免疫系统以及肝、肾功能不仅无明显的毒性,相反还能提高其免疫器官的重量和指数,显著提高Heps小鼠的白细胞和血小板计数,并能显著降低Heps小鼠的AST,ALT和BUN的异常升高。结论:BL对移植性肝癌Heps小鼠的抗肿瘤活性明显强于B,并且对Heps小鼠造血、免疫系统以及肝肾的毒性低,通过深入研究BL可望成为一种新型的抗癌药物。     

三肽化合物酪丝亮肽对巨噬细胞吞噬及肿瘤细胞杀伤功能的影响

目的：研究三肽化合物酪丝亮肽(YSL)对巨噬细胞(M(?))吞噬功能、肿瘤细胞杀伤功能和细胞因子分泌功能的影响。方法：通过碳粒廓清实验观察YSL对小鼠M(?)吞噬功能的影响,采用MTT法观察YSL对腹腔M(?)杀伤人肝癌细胞BEL-7402和小鼠黑色素瘤细胞B16-F10作用的影响,用ELISA法观察YSL对M(?)株RAW264．7分泌细胞因子IL-1β和NO功能的影响。结果：YSL 80,160,320μg·kg~(-1)·d~(-1)均能够明显增强小鼠M(?)的吞噬功能(P＜0．01),YSL各浓度(0．1,1,10,100 mg·L~(-1))在体外明显增强小鼠腹腔M(?)对肿瘤细胞BEL-7402和B16-F10的杀伤作用(P＜0．01)。YSL可以促进细胞毒效应分子IL- 1β和NO的分泌合成,NO和IL-1β水平分别在YSL作用12 h,24 h时达到高峰。结论：YSL可以增强M(?)吞噬功能,增强对肿瘤细胞的杀伤作用,促进细胞因子IL-1β和NO分泌。     

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.

---

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.     

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.     

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.     

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.