过氧化氢亚急性吸入毒性研究

本研究应用Ｈ２Ｏ２蒸气（５．４，３２．１ｍｇ／ｍ３）进行大鼠亚急性吸入染毒。大鼠吸入Ｈ２Ｏ２蒸气后，发现血清ＡＫＰ和ＡＣＰ活性增高，全血ＣＡＴ及肺组织ＳＤＨ活性降低。同时还发现肺组织ＧＳＨ含量明显降低，ＭＤＡ含量显著升高。Ｈ２Ｏ２对呼吸系统不仅有刺激作用还可诱发对肺脏的氧化性损伤。     

吸入肼对大鼠肝肺组织某些生化指标的影响

研究吸入不同浓度的肼２小时，对大鼠肝肺组织中的脂质过氧化产物丙二醛（ＭＤＡ）、谷胱甘肽（ＧＳＨ）和超氧化物歧化酶（ＳＯＤ）含量的影响。研究发现，大鼠吸入肼后肝肺组织中的ＭＤＡ含量明显升高，ＧＳＨ含量则明显下降，ＳＯＤ含量在肺组织中明显下降，而在肝组织中无明显变化。本研究说明肼引起的氧化性损伤是其肝肺毒作用的一个重要方面。     

锌和硒对CCl4肝损害保护作用的实验研究

实验用ＳＤ大鼠。ＣＣｌ４经口染毒５００ｍｇ／ｋｇ。每周２次。连续染毒６周。染毒的同周分别给予锌（６ｍｇ／ｋｇ混入饲料中喂饲）。硒（３μｇ／ｍｌ饮用水供饮用）及ＶｉｔＥ（１０ｍｇ／ｋｇ腹腔注射，每周二次），共给１０周。于每隔两周处死一批动物，１０周实验的结果显示，ＣＣｌ４染毒后表现为ＳＧＰＴ活性、ＭＤＡ含量升高，ＧＳＨ、Ｐ４５０及ｂ５的含量下降，Ｚｎ、Ｓｅ和ＶｉｔＥ处理组其ＳＧＰＴ活性升高的幅度低于ＣＣｌ４组，上升的峰值也迟两周出现。停止染毒后，Ｚｎ，Ｓｅ组ＳＯＰＴ活性迅速下降，于第八周恢复对照组水平，并比ＶｉｔＥ组早两周达正常。各处理组ＭＤＡ含量值也表现为上升的幅度低，染毒停止后迅速恢复。Ｚｎ组ＧＳＨ第六周才有显著下降，第八周即恢复，Ｓｅ组则在整个观察期未见有显著的下降。各组染毒后细胞色素Ｐ４５０含量均下降。除Ｚｎ组于第八周达对照组水平外，其他组至第一周仍低于阴性组，细胞色素ｂ５含量Ｚｎ组、Ｓｅ组和ＶｉｔＥ组则于第四周开始下降，第八周恢复。组织病理学改变表现为ＶｉｔＥ、Ｚｎ、Ｓｅ组肝损害程度轻于ＣＣｌ４组。在抗纤维化上Ｓｅ和Ｚｎ优于ＶｉｔＥ。     

铅诱发大鼠脂质过氧化作用及毒作用机制研究

本研究表明，醋酸铅染毒大鼠肝和脑组织中氧自由基的信号随着染毒剂量的增高而增高，表明铅染毒可诱发大鼠体内氧自由基产生；血、肝、和脑组织中ＭＤＡ水平升高程度与染毒剂量呈极显著正相关性；红细胞内ＳＯＤ活性下降和ＧＳＨ－Ｐｘ酶活性轻度升高，使得机体清除自由基和抗氧化的能力下降，造成体内的氧自由基蓄积，从而诱发脂质过氧化作用，推测这可能是铅的毒作用机制之一。     

炊事工人血浆VitC、VitE、β-胡萝卜素、LPO、红细胞SOD值的检测及相关分析

对３６名烹调油烟接触者和３０名非接触者血浆ＶｉｔＣ、ＶｉｔＥ、β－胡萝卜素、ＬＰＯ、红细胞ＳＯＤ水平进行研究,结果表明,烹调油烟接触组血浆中ＶｉｔＣ、ＶｉｔＥ、β－胡萝卜素的含量、红细胞ＳＯＤ的活性较非接触组的低,ＬＰＯ较非接触组的高（Ｐ＜０．０１）,并与接触ＣＯＦ浓度呈一定程度的直线相关;接触ＣＯＦ浓度越高,血浆中ＶｉｔＣ、ＶｉｔＥ、β－胡萝卜素的含量、红细胞ＳＯＤ的活性平均值越低,血浆ＬＰＯ含量平均值越高。提示烹调油烟可能损害机体内活性氧防卫生系统,导致体内氧自由基反应及脂质过氧化反应加剧。     

炊事工人血浆VitC,VitE,β—胡萝卜素,LPO,红细胞SOD值的检？…

对３６名烹调油烟接触者和３０名非接触者血浆ＶｉｔＣ、ＶｉｔＥ、β胡萝卜素,ＬＰＯ、红细胞ＳＯＤ水平进行研究,结果表明,烹调油烟接触组血ＶｉｔＣ、ＶｉｔＥ、β－胡萝卜素的含是细胞ＳＯＤ的活怀较非接触组的低,ＬＰＯ较非接触组的高,并与接触ＣＯＦ浓度呈一定程度的直线相关;接触ＣＯＦ浓度越高,血浆中ＶｉｔＣ、ＶｉｔＥ、β－胡萝卜素的含量,红细胞ＳＯＤ的活性平均值越低,血浆ＬＰＯ含量平均值越高,提示烹调油烟     

姜黄素对鼠体内SOD活性和MDA含量的影响

目的：观察姜黄素对成年小鼠及老年大鼠体内超氧化物歧化酶（ＳＯＤ）和丙二醛（ＭＤＡ）含量的影响。方法：选用成年ＮＩＨ小鼠，每日腹腔注射姜黄素共７ｄ，观察血浆、脑及肝脏组织的ＳＯＤ活性及ＭＤＡ含量。选用雄性ＳＤ老年大鼠（＞２８月龄），用０．０２％姜黄素水溶液作为饮水，连续给药９ｗｋ，动态观察给药前及给药后９ｗｋ内血浆中ＳＯＤ和ＭＤＡ的含量。结果：姜黄素给药小鼠血浆及脑组织的ＭＤＡ含量下降，血浆、脑及肝脏组织的ＳＯＤ活性均明显提高，呈现一定的剂量依赖关系。老年大鼠给药后血浆中的ＭＤＡ含量明显降低，血浆ＳＯＤ的活性在给药后３ｗｋ呈现一过性升高。结论：姜黄素有抑制成年小鼠和老年大鼠体内脂质过氧化过程的作用，该作用除了与其本身的抗自由基效应有关外，还与其提高机体的ＳＯＤ活性作用有一定关系。     

绞股蓝总苷对老龄大鼠的抗氧化作用观察

目的：观察口服绞股蓝总苷对老龄大鼠的抗氧化作用。方法：测定药后大鼠红细胞超氧化物歧化酶（ＳＯＤ）和全血谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）等抗氧化酶含量及肾上腺内维生素Ｃ（ＶｉｔＣ）含量。结果：绞股蓝总苷４０和２０ｍｇ／ｋｇ连续用药２０ｄ能升高大鼠红细胞ＳＯＤ和全血ＧＳＨ－Ｐｘ酶活力,且能降低大鼠肾上腺皮质中ＶｉｔＣ含量。结论：绞股蓝总苷能增强老龄大鼠机体抗氧化能力及提高肾上腺皮质的功能。     

锰和锗对CCl4肝损害保护作用的实验研究

实验用ＳＤ大鼠。ＣＣｌ４５００ｍｇ／ｋｇ经口染毒。每周两次。连续染毒６周。于染毒的同时分别给予锰４ｍｇ／ｋｇ和锗－１３２１０ｍｇ／ｋｇ混入饲料中喂饲。ＶｉｔＥ以１０ｍｇ／ｋｇ经腹腔注射。每周两次。每两周处死一批动物。结果显示，锰组、锗－１３２组和ＶｉｔＥ组染毒后，ＳＧＰＴ在第二周增加的幅度均低于ＣＣｌ４组，并于停止染毒后迅速下降。且锰组、锗－１３２组比ＶｉｔＥ组早两周恢复正常水平。各处理组肝匀浆中ＭＤＡ在整个观察期上升的幅度均低于ＣＣｌ４组。在染毒停止后第８周恢复正常。锰组肝匀浆中ＧＳＨ含量于整个染毒期均未见显著的下降，锗－１３２组于第４周降低显著，第８周恢复。细胞色素Ｐ４５０染毒后各组均显著降低并持续至第１０周，ｂ５值锰组和锗－１３２组分别在第四周及第六周有一最低值。均于第八周恢复。病理结果显示，锰组和锗－１３２组其纤维化、脂变的程度明显减轻。提示锰、和锗－１３２对ＣＣｌ４肝损害有一定的保护作用，其效果优于ＶｉｔＥ。     

钒酸钠对患糖尿病大鼠某些器官组织SOD活性的影响

目的 探讨钒酸钠对血浆、肝、肾组织中ＳＯＤ活性的影响,以及ＳＯＤ活性与糖尿病（ＤＭ）动物肝、肾组织学变化的关系。方法 ６０只大鼠随机分为正常对照（ＮＣ）组,自由饮用ＮａＣｌ水,矾酸钠（Ｖ）组,自由饮用ＮａＣｌ＋Ｎａ３ＶＯ４（０．５ｍｇ／ｍｌ）;糖尿病（Ｄ）组;钒酸钠＋糖尿病（ＤＶ）组。测定血、肝、肾组织中的ＳＯＤ活性。并作病理组织学检查。结果 Ｄ组大鼠血浆、肝、肾组织中ＳＯＤ活性降低,ＤＶ组血浆、     

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.     

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.     

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.