珠蚌多糖对四氯化碳诱导肝细胞损伤的保护作用

目的 研究珠蚌多糖(HCP)对肝细胞损伤的保护作用及其机制.方法 培养L-02型肝细胞,用四氯化碳(CCL)体外诱导肝细胞损伤,检测培养上清液中天门冬氨酸转挟酶(AST)和丙氨酸氨基转换酶(ALT)水平,测定上清液中丙二醛(MDA)的含量扣过氧化物岐化酶(SOD)活力,MTT法检测细胞存活和增殖活性.结果 珠蚌多糖(25,250及1000μg·L-1)剂量组均可明显降低由CCl4升高的肝细胞培养上清波中AST争ALT水平及MDA含量,还可提高CCl4降低的肝细胞存活率和SOD活力.结论 提示珠蚌多糖对肝细胞损伤有直接保护作用,该作用可能与其抗氧化作用有关.     

二至丸保肝有效部位群对体外肝细胞损伤的保护作用

目的 研究二至丸保肝有效部位群(50％乙醇部位)(EFEP)对体外肝细胞损伤的保护作用及机理.方法 培养L-O2型肝细胞,采用四氯化碳(CCl4)和过氧化氢(H2O2)体外诱导肝细胞损伤,检测培养上清液中AST和ALT水平,测定上清液中丙二醛(MDA)的含量、过氧化物岐化酶(SOD)及谷胱甘肽过氧化物酶(GSH-Px)活性,MTT法检测细胞存活和增殖活性.结果 EFEP0.32-40 μg/ml明显降低由CCl4所致肝细胞培养上清液中AST和ALT水平和MDA含量的升高,也显著提高由CCl4所致肝细胞存活率和SOD活力及GSH-Px活性的降低.EFEP 0.32-40 μg/ml使H2O2升高的肝细胞培养上清液中AST和ALT水平及MDA含量明显降低,还显著提高由H2O2降低的肝细胞存活率和SOD活力及GSH-Px活性.结论 EFEP对体外肝细胞损伤有较强的保护作用.该作用可能与其抗氧化作用有关.     

二至丸提取物对体外肝细胞损伤的保护作用

 目的：研究二至丸乙酸乙酯提取物(ethyl acetate extractsof Erzhi pill,EAEP)对体外肝细胞损伤的保护作用及其机理。方法：培养L-O2型肝细胞,采用CCl4和H2O2体外分别诱导肝细胞损伤,检测培养上清液中天门冬氨酸转换酶(AST)和丙氨酸氨基转换酶(ALT)水平,测定上清液中丙二醛(MDA)的含量和过氧化物岐化酶(SOD)活力及谷胱甘肽过氧化物酶(GSH-Px)活性,MTT法检测细胞存活和增殖活性。结果：① EAEP(0.32～40 μg?mL-1)剂量组可明显降低由CCl4所致肝细胞培养上清液中AST和ALT水平及MDA含量的升高,还可提高由H2O2所致肝细胞存活率和SOD活力及GSH-Px活性的降低。② EAEP(0.32～40 μg?mL-1)剂量组可使H2O2升高的肝细胞培养上清液中ALT和ALT水平及MDA含量明显降低或恢复,还可提高CCl4降低的肝细胞存活率和SOD活力及GSH-Px活性。结论：提示AEEP对体外肝细胞损伤有直接保护作用,该作用可能与其抗氧化作用有关。     

龙眼参多糖对四氯化碳诱导大鼠原代肝细胞损伤的保护作用

目的:研究龙眼参多糖(LYS)对大鼠原代肝细胞损伤的保护作用及其机制。方法:用四氯化碳(CCl4)体外诱导大鼠原代肝细胞损伤,检测培养上清液中天门冬氨酸转移酶(AST)和丙氨酸氨基转移酶(ALT)水平,测定肝细胞中丙二醛(MDA)和谷胱甘肽(GSH)含量,四甲基偶氮唑盐(MTT)法检测细胞活性。结果:与模型组比较,LYS组AST和ALT水平及肝细胞MDA含量明显降低,肝细胞存活率和GSH含量升高。结论:LYS对大鼠原代培养肝细胞损伤有直接保护作用,机制可能与其抗氧化作用有关。     

二至丸水提物对体外肝细胞损伤的保护作用

目的研究二至丸水提物（aqueous extract of Erzhi Pill,AEEP）对体外肝细胞损伤的保护作用及其机制。方法培养L-O2型肝细胞,采用H2O2和CCl4体外分别诱导肝细胞损伤,检测培养上清液中天门冬氨酸转换酶（AST）和丙氨酸氨基转换酶（ALT）水平,测定上清液中丙二醛（MDA）的含量和过氧化物岐化酶（SOD）活力,MTT法检测细胞存活和增殖活性。结果①AEEP（0.32~40μg/ml）剂量组可明显降低由H2O2升高的肝细胞培养上清液中AST和ALT水平及MDA含量,还可提高H2O2降低的肝细胞存活率和SOD活力;②AEEP（0.32~40μg/ml）剂量组可使CCl4升高的肝细胞培养上清液中ALT和ALT水平及MDA含量明显降低或恢复,还可提高CCl4降低的肝细胞存活率和SOD活力。结论提示AEEP对体外肝细胞损伤有直接保护作用,该作用可能与其抗氧化作用有关。     

金丝桃苷对四氯化碳诱导肝细胞损伤的保护作用

目的研究金丝桃苷(hyperfine,HP)对四氯化碳(CCl4)诱导肝细胞损伤的保护作用及其机制。方法用CCl4体外诱导人正常肝细胞L-02损伤,检测培养上清液中天门冬酸氨基转移酶(AST)和丙氨酸氨基转移酶(ALT)水平,测定肝细胞中丙二醛(MDA)和谷胱甘肽(GSH)的含量,四甲基偶氮唑盐微量酶反应比色(MTT)法检测肝细胞存活率。结果金丝桃苷可明显降低由CCl4升高的肝细胞培养上清液中ALT和AST水平及肝细胞MDA含量,还可提高由CCl4降低的肝细胞存活率和GSH含量。结论金丝桃苷对人肝细胞氧化性损伤有直接保护作用,这可能与金丝桃苷抑制抗氧化酶活性和抗自由基活性有关。     

南沙参多糖对四氯化碳损伤原代培养大鼠肝细胞保护作用的研究

目的:探讨南沙参多糖(RAPS)对四氯化碳(CCl4)损伤原代培养大鼠肝细胞的保护作用及其机制。方法:通过原位灌流法分离大鼠肝细胞,培养36h后加入RAPS,同时造成CCl4损伤,分别于损伤24h和48h时检测培养液中丙二醛(MDA)的含量、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)的活性,48h后用MTT法测定肝细胞存活率。结果:RAPS对CCl4引起的ALT、AST活力的升高有抑制作用,同时抑制MDA的产生及肝细胞损伤造成的SOD活性及GSH-PX活性的降低。而且能明显改善肝细胞存活率。结论:RAPS能有效抑制CCl4造成的原代培养大鼠肝细胞损伤,机制可能与其抗氧化作用有关。     

灯盏乙素对异烟肼和利福平合用致小鼠肝损伤的保护作用

目的:观察灯盏乙素对异烟肼(INH)和利福平(RFP)合用致小鼠肝损伤的保护作用.方法:小鼠每天同时灌胃RFP和INH各100 mg·kg-1,2 h后灌胃灯盏乙素50,100,200 mg·kg-1,qd,连续给药10 d,末次给药16 h后,取血和各器官组织,测定肝、脾和胸腺指数、血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)的活性、肝匀浆中超氧化物歧化酶(SOD)、脂质过氧化物丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)以及一氧化氮(NO)的含量.结果:灯盏乙素能显著降低RFP和INH合用致肝损伤小鼠的肝指数、血清ALT和AST活性、肝匀浆中的MDA和NO含量,并能显著提高肝匀浆中的SOD和GSH-Px活性.结论:灯盏乙素对RFP和INH合用致小鼠肝损伤具有明显的保护作用,可能与其抗脂质过氧化及调节体内NO水平有关.     

胰岛素对大鼠肝细胞损伤的保护作用

目的:探讨胰岛素对大鼠肝细胞损伤是否具有保护作用。方法:胶原酶原位灌流分离大鼠肝细胞并原代培养,分别用脂多糖(LPS)及胰岛素处理肝细胞,12 h后检测肝细胞损伤及存活率。结果:LPS可引起肝细胞损伤,使丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)增高;胰岛素可减轻上述肝细胞损伤(ALT活性降低55.5%、AST活性降低24.4%,P<0.01),提高肝细胞存活率(P<0.01)。结论:胰岛素可减少ALT和AST释放,促进肝细胞存活,减轻LPS直接诱导的肝细胞损伤,保护受损的肝细胞。     

玉郎伞多糖对四氯化碳诱导大鼠原代肝细胞损伤的保护作用

目的:研究玉郎伞多糖(YLS)对大鼠原代肝细胞损伤的保护作用及其机制。方法:采用IV型胶原酶灌流法分离大鼠肝细胞进行原代培养,用四氯化碳(CCl4)体外诱导肝细胞损伤,检测培养上清液中天门冬氨酸转换酶(AST)和丙氨酸氨基转换酶(ALT)水平,测定肝细胞中丙二醛(MDA)和谷胱甘肽(GSH)含量,MTT法检测细胞存活和增殖活性。结果:YLS(0.125~1.000g.L-1)可明显降低由CCl4升高的肝细胞培养上清液中AST和ALT水平及肝细胞MDA含量,还可提高CCl4降低的肝细胞存活率和GSH含量。结论:提示YLS对大鼠原代培养肝细胞损伤有直接保护作用,该作用可能与其抗氧化作用有关。     

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.

     

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.     

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.     

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.