三尖杉酯类生物碱对L615及P388白血病细胞cAMP含量的影响

实验证明,三尖杉酯类生物碱对某些动物移植性白血病和实体瘤有不同程度的疗效。在治疗剂量下,三尖杉酯碱能抑制肿瘤细胞有丝分裂,降低肝、脾和肿瘤组织的核酸含量,明显抑制DNA合成。三尖杉酯碱对白血病L1210杀伤动力学研究表明,它是一个细胞周期非特异性抗肿瘤药,但对S期细胞有强烈杀伤作用,对G_0期细胞也有一定影响。临床     

小鼠造血干细胞和P388白血病干细胞对5种抗癌药的敏感性比较

用脾集落形成法比较了5种抗癌药对小鼠造血干细胞(NCFU-S)和P₃₈₈白血病干细胞(LCFU-S)的作用。三尖杉酯碱、半合成三尖杉酯碱、高三尖杉酯碱和环磷酰胺对两类干细胞作用的剂量—反应曲线呈指数形,效能比依次为5.15,6.01,7.96和9.98。阿糖胞苷对NCFU-S无明显作用,但对LCFU-S杀伤作用强,大剂量时剂量—反应曲线趋于水平。当三尖杉酯碱、高三尖杉酯碱和半合成三尖杉酯碱的剂量分别低于0.30,0.28和0.75mg/kg时,对LCFU-S无明显作用,剂量—反应曲线上出现“肩形”,提示LCFU-S在小剂量三尖杉酯类生物碱作用下,有一受亚致死性损伤后修复过程。     

小鼠造血干细胞和P_(388)白血病干细胞对5种抗癌药的敏感性比较

用脾集落形成法比较了5种抗癌药对小鼠造血干细胞(NCFU-S)和P_(388)白血病干细胞(LCFU-S)的作用。三尖杉酯碱、半合成三尖杉酯碱、高三尖杉酯碱和环磷酰胺对两类干细胞作用的剂量—反应曲线呈指数形,效能比依次为5.15,6.01,7.96和9.98。阿糖胞苷对NCFU-S无明显作用,但对LCFU-S杀伤作用强,大剂量时剂量—反应曲线趋于水平。当三尖杉酯碱、高三尖杉酯碱和半合成三尖杉酯碱的剂量分别低于0.30,0.28和0.75mg/kg时,对LCFU-S无明显作用,剂量—反应曲线上出现“肩形”,提示LCFU-S在小剂量三尖杉酯类生物碱作用下,有一受亚致死性损伤后修复过程。     

三尖杉酯碱正，负电荷脂质体在大鼠体内的分布

三尖杉酯碱（harringtonine,H)是从三尖杉属植物中分离到的抗肿瘤有效成分，对急性及慢性粒细胞白血病，急性单核细胞白血病及红白血病匀有肯定的疗效，但也具有毒性较大及易复发的缺点，脂质体可以改变多种药物在动物体内的组织分布，提高药物的选择性，增加疗效和降低毒性（4-6)，因而越来越受到重视，本文目的是比较三尖杉酸碱正，负脂质体（harringtonine positively and negatively charged liposome,HL( ),HL(-)和游离三尖杉酯碱（harrinmgtonine free-form ,HF)在动物体内的组织分布及它们的急性毒性，观察不同的三尖杉酯碱脂质体是否能提高H在某些组织中的分布量，能否促进H秀过血脑屏障及血睾屏障，为扩大H临床应用范围及临床合理用药提供依据。     

三尖杉属植物中生物碱的研究——Ⅷ.二种新的抗癌三尖杉酯碱生物碱的结构和半合成

从安徽产三尖杉(Cephalotaxusfortunei Hook f.)弱碱中分到二种新的抗癌生物碱,命名为新三尖杉酯碱(neoharringonine,1)和脱水三尖杉酯碱(anhydroharringtonine,2)。从本种植物中还首次分到二个已知生物碱:脱氧三尖杉酯碱(deoxyharringtonine,3)和异三尖杉酯碱(isoharringtonine,4)。     

三尖杉属植物中生物碱的研究——Ⅷ.二种新的抗癌三尖杉酯碱生物碱的结构和半合成

从安徽产三尖杉(Cephalotaxusfortunei Hook f.)弱碱中分到二种新的抗癌生物碱,命名为新三尖杉酯碱(neoharringonine,1)和脱水三尖杉酯碱(anhydroharringtonine,2)。从本种植物中还首次分到二个已知生物碱:脱氧三尖杉酯碱(deoxyharringtonine,3)和异三尖杉酯碱(isoharringtonine,4)。     

用改进逆流分配法分离三尖杉酯碱和高三尖杉酯碱

对三尖杉酯碱和高三尖杉酯碱混合物的分离利用经改进的逆流分配法，用经ｐＨ５缓冲液饱和的氯仿作流动相，经氯仿饱和的ｐＨ５磷酸氢二钠－枸橼酸作固定相，醋酸乙酯∶丙酮（６∶２．５）作展开剂，碱性硅胶板作薄层板，经对５批混合物进行分离，均分别获得三尖杉酯碱和高三尖杉酯碱的白色结晶。各项指标检查均符合标准。     

尿,血,细胞匀浆中高三尖杉酯碱的高效液相色谱测定法

尿、血、细胞匀浆中高三尖杉酯碱的高效液相色谱测定法山东省劳动卫生职业病防治研究所济南２５０００１邵华三尖杉科三尖杉属植物为我国特有，高三尖杉酯碱（以下简称ＨＨＴ）是其中分离出来的－种抗癌药物，是治疗急性非淋巴细胞白血病的有效药物。目前，国内外对该药的...     

高三尖杉酯碱对白血病原癌基因bcl-2、c-myc、抑癌基因p15的影响

目的探讨高三尖杉酯碱对白血病治疗作用的机制。方法用细胞培养、DNA片段凝胶电泳、Western blot和cDNA阵列杂交等方法检测高三尖杉酯碱对白血病HL-60细胞凋亡及原癌基因表达的影响。结果高三尖杉酯碱使HL-60细胞、bcl-2蛋白表达明显较低,c-myc表达较弱,而p15表达较强。结论高三尖杉酯碱抑制HL-60细胞增殖、诱导其分化和凋亡,其机制可能与高三尖杉酯碱下调原癌基因bcl-2、c-myc及上调抑癌基因p15有关。     

抗肿瘤植物药的非抗肿瘤临床应用

<正> 抗肿瘤植物药是抗肿瘤药物的重要组成部分。已有的植物类抗肿瘤药在肿瘤的治疗中发挥着一定作用,而且在其他疾病尤其是疑难杂病治疗中显示出活力。本文就抗肿瘤药物三尖杉酯碱类、长春碱类、秋水仙碱类、鬼臼毒素、喜树碱和紫杉醇在临床中用于治疗非肿瘤疾病的现状作一综述。1 三尖杉酯碱和高三尖杉酯碱 三尖杉酯碱的早期研究证明,它可抑制蛋白质合成的起始阶段,以后的进一步研究表明,它对DNA合成也有抑制作用,还能诱导细胞分化,提高胞内cAMP含量。高三尖杉酯碱作用基本上与三尖杉酯碱相同,临床证明两药均对急性非淋巴性白血病有较高疗效。两药的非抗肿瘤作用主要有:(1)防治青光眼     

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.