黄精多糖抗肿瘤作用的实验研究

目的研究黄精多糖对H22实体瘤、S180腹水瘤的生长抑制作用和对荷瘤小鼠免疫调节作用。方法小鼠接种H22实体瘤或S180腹水瘤后随机分组,灌胃给予不同剂量[100、200、400mg/(kg.d)]的黄精多糖,以生理盐水和环磷酰胺为空白对照组和阳性对照组,计算黄精多糖对小鼠H22实体瘤生长的抑制率,脾脏指数和胸腺指数,以及S180腹水型荷瘤小鼠的存活时间。结果给予黄精多糖灌胃的荷瘤小鼠的脾脏指数和胸腺指数显著增加;低、中、高剂量的黄精多糖对H22实体瘤的抑瘤率分别是(34.93、43.44、56.25)%;中、高剂量的黄精多糖可以显著延长S180腹水型荷瘤小鼠的存活时间。结论黄精多糖有显著的抗肿瘤作用和免疫调节活性。     

灵芝三萜组分GLE的体内外抗肿瘤作用

目的:评价灵芝三萜组分GLE的体内外抗肿瘤作用。方法:建立小鼠S180实体瘤和腹水瘤两种模型,观察GLE对实体瘤抑瘤率和腹水瘤生命延长率的影响;采用MTT法检测GLE对人鼻咽癌细胞CNE1和CNE2的体外抗肿瘤活性。结果:3个剂量(125,250,500 mg.kg-1)GLE对S180实体瘤小鼠均具有一定的抑制作用(P<0.05),500 mg.kg-1组的瘤重抑制百分率达51.4%;对S180腹水瘤小鼠具有明显的延长存活期作用,500 mg.kg-1组的生命延长率为52.0%(P<0.05);体外对人鼻咽癌低分化细胞CNE2有一定的抑制作用。结论:GLE对小鼠肉瘤S180及人鼻咽癌低分化细胞CNE2的生长有一定的抑制作用。     

肿节风总黄酮对小鼠肉瘤S_(180)的抑瘤作用

目的观察肿节风总黄酮对小鼠肉瘤S180实体瘤和腹水瘤的作用,为开发高效低毒的抗肿瘤新药提供依据。方法采用动物整体实验方法,观察肿节风总黄酮对S180荷瘤小鼠实体瘤及腹水瘤的抑瘤作用及生命延长率。结果肿节风总黄酮对S180实体瘤的抑瘤率为20.7%～60.1%,对S180腹水瘤的延长率为36.8%。结论肿节风总黄酮有一定的抗肿瘤作用及生命延长率。     

玄参多糖抗肿瘤作用的实验研究

目的玄参多糖抗食管癌Eca-109肿瘤、肉瘤S180肿瘤的作用。方法小鼠接种Eca-109实体瘤或S180腹水瘤24 h后随机分组,灌胃给予不同剂量玄参多糖[(200、400、800 mg/(kg?d)]。实验结束时,计算玄参多糖对小鼠Eca-109实体瘤生长的抑制率,脾脏指数和胸腺指数,以及S180腹水型荷瘤小鼠的存活时间。结果与环磷酰胺组比较,给予玄参多糖灌胃的荷瘤小鼠的脾脏指数和胸腺指数显著增加;低、中、高剂量的玄参多糖对Eca-109实体瘤的抑瘤率分别是18.59%、26.13%、36.17%。玄参多糖各剂量组均可显著延长S180腹水型荷瘤小鼠的存活时间,其中中、高剂量组尤为明显。结论玄参多糖表现出一定的抑制肿瘤作用和保护机体免疫器官。     

抑癌因子腹腔注射对小鼠实体瘤生长的抑制作用

目的：观察抑癌因子腹腔注射对小鼠实体瘤生长的影响。方法：小鼠右腋皮下分别接种肝癌和S180肉瘤细胞，24小时后，实验组小鼠腹腔注射抑癌因子，对照组小鼠腹腔注射生理盐水，连续七天，第八天处死小鼠，剥离出瘤块称重。结果：肝癌和S180小鼠肿瘤平均重量为0．65g和0．64g，相应的对照组小鼠肿瘤的平均重量为1．41g和．134g，P值均小于0．01，抑瘤率分别为53．9％和52．2％。结论：抑癌因子腹腔注射对肝癌和S180小鼠实体瘤的生长有明显的抑制作用，其抑癌机理可能是通过启动细胞凋亡信号传递途径，诱导和加速癌细胞的凋亡。     

鸦胆子提取物对S180 小鼠抗肿瘤作用的实验研究

目的研究鸦胆子提取物对小鼠移植性肿瘤S180的抑制作用。方法建立小鼠腋下S180实体瘤模型,观察不同剂量鸦胆子提取物对小鼠抑瘤率及对免疫器官的影响;建立小鼠S180腹水瘤模型,观察不同剂量鸦胆子提取物对小鼠生存期的影响。结果鸦胆子提取物中、高剂量能明显抑制S180实体瘤的生长（P〈O．05）;抑瘤率分别为20．4％和24．6％。鸦胆子提取物低、中剂量可以延长S180腹水瘤小鼠的生存期（P〈O．05）,延长率为21％和18．5％。结论鸦胆子提取物有一定抗肿瘤的作用。     

一种新的喜树碱衍生物的抗肿瘤活性

对喜树碱衍生物7-乙基-10-(4-(1-哌啶基)-1-哌啶基)-甲酸酯基-喜树碱(CPT-11)进行了抗肿瘤活性和毒性试验。(?)小鼠腹腔接种L 1210(CDF_1),P 388(CDF_1),B16黑色素瘤(C57BL/6),S180(ICR)和MethA 肉瘤(BALB/c)。S 180和MethA 也可皮下接种。接种后第1,5,9天腹腔注射,静注或口服CPT-11,但带B16的小鼠要在接种后第1,5,9,13,17天给药。观察腹水瘤小鼠的存活时间和实体瘤的生长抑制作用。     

新疆软紫草多糖体内抗肿瘤作用研究

目的 研究新疆软紫草多糖对小鼠宫颈癌U14生长的抑制作用。方法 建立小鼠宫颈癌U14实体瘤与腹水瘤两种模型,观察软紫草多糖对实体瘤抑瘤率、胸腺和脾脏免疫器官重量和腹水瘤生命延长率的影响。结果 软紫草多糖3个剂量组对U14实体瘤小鼠均具有明显的抑制作用(P<0.05),对U14腹水瘤小鼠具有明显的延长存活期作用(P<0.05),中剂量组能明显增加U14实体瘤小鼠的脾指数,高、中剂量组能明显降低胸腺指数。结论 软紫草多糖对小鼠宫颈癌U14的生长有一定的抑制作用。     

复方氟尿嘧啶多相脂质体对S180荷瘤小鼠肿瘤生长抑制及其不良反应

目的:比较复方氟尿嘧啶多相脂质体(Co-5-FU)和氟尿嘧啶(5-FU)对小鼠肉瘤细胞系S180荷瘤小鼠的抗肿瘤作用及不良反应。方法:将小鼠肉瘤S180细胞悬液接种于小鼠背部皮下或腹腔,建立S180荷瘤小鼠实体瘤和腹水瘤模型。取70只小鼠,分成实验组(Co-5-FU)、阳性对照组(5-FU)和正常对照组,分别腹腔注射40 mg·kg~(-1)、20 mg·kg~(-1)、10 mg·kg~(-1)3种不同浓度的Co-5-FU和5-FU,正常对照组腹腔注射生理盐水。比较Co-5-FU和5-FU对实体瘤小鼠的肿瘤抑制率,腹水瘤小鼠的生命延长率,同时通过血生化和病理等检测观察2种药物对各脏器的不良反应。结果:与正常对照组比较,40 mg·kg~(-1)、20 mg·kg~(-1)、10 mg·kg~(-1) Co-5-FU对S180腹水瘤小鼠的生命延长率分别是52．7％,41．4％和31．9％(P＜0．05),对S180实体瘤小鼠的肿瘤抑制率分别是48．8％和39．2％和32．0％(P＜0．01);同等剂量Co-5-FU比5- FU引起的骨髓抑制轻(P＜0．05);40 mg·kg~(-1)5-FU可引起肝脏ALT、AST、GGP升高(P＜0．05)。结论: Co-5-FU比同等剂量的5-FU具有更强的抗肿瘤作用,对心脏、肾脏、肝脏、骨髓的不良反应明显小于5- FU。     

沙枣提取物对某些肿瘤细胞株及小鼠实体瘤和腹水瘤的抑制作用

目的探讨沙枣提取物对4种肿瘤细胞株及小鼠实体瘤和腹水瘤的抑制作用及机制。方法应用MTT法检测了提取物对4个肿瘤细胞株生长的抑制作用,检测提取物对实体瘤肿瘤生长的抑制率和腹水瘤小鼠的生命延长率,探讨提取物对肿瘤细胞凋亡的影响及机制。结果体外实验中观察到高中低剂量组具有明显抑制4种肿瘤细胞生长作用(P<0.01)。体内实验观察到沙枣提取物高中低剂量均有抑制S180实体瘤小鼠肿瘤生长、延长S180腹水瘤小鼠的生存时间作用。形态学观察发现提取物诱导了4种肿瘤细胞的凋亡,提取物诱导4种肿瘤细胞早期凋亡率在14.1%～24.5%之间,明显高于未处理肿瘤细胞(P<0.05)。提取物处理T24细胞后,bax、caspase-3蛋白表达明显增强,bcl-2表达降低。结论在本试验条件下,沙枣提取物有抑制肿瘤生长作用,其机制可能与下调bcl-2表达和上调bax的表达,高表达caspase-3诱导肿瘤细胞凋亡有关。     

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.     

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.     

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.