氧化苦参碱对异丙肾上腺素致心肌肥厚大鼠心脏重构的保护作用研究

目的:研究氧化苦参碱对异丙肾上腺素致心肌肥厚大鼠心脏重构的保护作用,并探讨其作用机制。方法:给予Spraguedawley大鼠连续7 d皮下注射异丙肾上腺素5 mg/(kg·d),以建立大鼠心肌肥厚模型,观察氧化苦参碱对模型大鼠体质量,心肌肥厚指数,心肌组织形态学改变,超氧化物歧化酶、丙二醛及血清一氧化氮含量,一氧化氮合酶活性的影响。结果:氧化苦参碱可明显降低模型大鼠心肌肥厚指数、心肌细胞直径与横截面积、心肌间质胶原纤维含量;增强了血清及心肌组织中超氧化物歧化酶的活力,并相应地降低了脂质过氧化物丙二醛的含量;增强了血清中总一氧化氮合酶的活性,增加了血清一氧化氮的含量,但降低了诱导型一氧化氮合酶的活性。结论:氧化苦参碱对异丙肾上腺素致心肌肥厚大鼠有明显的心脏重构保护作用,其作用机制可能与提高机体抗氧化酶活性和调节血清一氧化氮含量/一氧化氮合酶活性有关。     

乌贼墨对高脂血症大鼠血脂代谢和抗氧化能力的影响

目的 探讨乌贼墨对实验性高脂血症大鼠血脂代谢和抗氧化能力的影响。方法 饲喂高脂饲料建立高脂血症大鼠模型，同时灌胃乌贼墨，剂量分别为50和200mg·kg^-1，连续30d。分别测定大鼠血清总胆固醇（TC），甘油三酯（TG），低密度脂蛋白胆固醇（LDL—c），高密度脂蛋白胆固醇（HDL-c）和一氧化氮（NO）含量，以及大鼠血清和肝脏丙二醛（MDA）含量，超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH—Px）活性。结果乌贼墨能显著性降低模型大鼠血清中的TC，TG和LDL-c含量，升高HDL-C，降低动脉粥样硬化指数（LDL-c／HDL-c）；显著提高高脂血症大鼠血清中NO含量；显著降低血清及肝组织中MDA含量，提高SOD和GSH—Px活性。结论乌贼墨可通过调节机体血脂代谢、提高机体内源性抗氧化酶活性，降低机体的过氧化水平，有效预防高脂血症的形成。     

车前子对高脂血症大鼠血脂水平及抗氧化作用的影响

目的:研究车前子对高脂血症大鼠血脂水平及抗氧化作用的影响.方法:用高脂饲料喂饲健康成年SD大鼠3个月,诱发高脂血症的同时,分别加入不同剂量的车前子,观察其对血脂及抗氧化作用的影响.结果:车前子可明显降低大鼠血清胆固醇(TC)、三酰甘油(TG)和脂质过氧化物(MDA)含量,提高高密度脂蛋白胆固醇(HDL-C)及HDL-C/TC比值,并且还能提高超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性及一氧化氮(NO)含量.结论:车前子能有效的降低高脂血症大鼠血脂水平,提高抗氧化能力.     

大黄酸固体分散体的制备及对大鼠血脂的影响

目的以聚乙烯吡咯烷酮为载体制备大黄酸固体分散体,考察其对大鼠血脂及抗氧化能力的影响。方法差示扫描量热法和红外光谱法对固体分散体进行分析。利用高脂饲料及脂肪乳剂建立SD大鼠高脂血症动物模型,大鼠分别灌胃给予大黄酸及大黄酸固体分散体,连续给药8周后测定总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和丙二醛(MDA)含量,测定超氧化物岐化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活力。结果大黄酸固体分散体能显著降低高脂血症大鼠血清中TC、TG、LDL-C含量(P<0.05);升高血清中HDL-C含量(P<0.05);提高SOD和GSH-Px活力;降低MDA含量(P<0.05)。结论以聚乙烯吡咯烷酮为载体制备的大黄酸固体分散体对高脂血症大鼠有降血脂及抗氧化作用。     

南极磷虾油对高脂血症大鼠血脂和抗氧化力的影响

目的探讨南极磷虾油对实验性高脂血症大鼠血脂和抗氧化力的影响。方法高脂饲料建立高脂血症大鼠模型,分别灌胃50,100和500 mg.kg-1南极磷虾油,连续30 d,测定大鼠血清总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C),高密度脂蛋白胆固醇(HDL-C)、血清一氧化氮(NO)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)以及丙二醛(MDA)水平。结果南极磷虾油能显著降低高脂血症大鼠血清中的TC、TG和LDL-C含量,降低动脉粥样硬化指数(AI)。提高大鼠血清中NO含量,提高SOD和GSH-PX活性,降低MDA含量。结论南极磷虾油对高脂血症大鼠具有调血脂的作用和抗氧化作用,其抵抗动脉粥状硬化方面的作用优于深海鱼油。     

火麻仁油对高脂血症大鼠血脂代谢及保肝作用研究

目的:探讨火麻仁油对高脂血症大鼠血脂代谢及肝脏的保护作用。方法:采用高脂饲料建立大鼠高脂血症模型,随机分为正常对照组、高脂模型组、火麻仁油高剂量组1.5 g·kg-1、中剂量组1.0 g·kg-1、低剂量组0.5 g·kg-1和血脂康阳性对照组(0.5 g·kg-1),连续给药35 d,观察不同剂量火麻仁油对高脂血症大鼠血清中总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、超氧化物岐化酶(SOD)、丙二醛(MDA)、丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)及肝脏中超氧化物岐化酶(SOD)和丙二醛(MDA)等生化指标的影响。结果:与模型组比较,火麻仁油各剂量组均能明显降低高脂血症模型大鼠血清中TC、TG、ALT的含量以及动脉粥样硬化指数(P<0.05或P<0.01)、并显著提高血清和肝脏中SOD酶活性(P<0.01);中、高剂量可以显著性地降低高脂血症模型大鼠血清AST、MDA含量(P<0.01);高剂量可以显著降低血清LDL-C以及肝脏中MDA含量(P<0.01)。结论:火麻仁油对高脂血症大鼠具有良好的降血脂的作用,而且具有较好的肝脏保护作用,其作用机制可能与改善脂质代谢和增强机体抗氧化能力有关。     

虎杖苷对缺血梗死型大鼠的心肌保护作用研究

目的研究虎杖苷对高脂血症引起的心肌缺血梗死型大鼠的心脏保护作用。方法以高能量饲料配合丙硫氧嘧啶诱导高脂血症;并联合大剂量VD3和垂体后叶素造成大鼠心肌缺血模型;分期测定三酰甘油（TG）、血清总胆固醇（TC）、D-脂蛋白（LDL）及d-脂蛋白（HDL）的含量;并测量心功能参数;光镜技术观察心肌形态学变化。结果虎杖苷具有降低TC、TG、D-脂蛋白及升高d-脂蛋白的作用,可以改善心肌缺血大鼠心脏功能;病理组织学显示,虎杖苷可减轻高脂血症大鼠心肌纤维结构的异常改变。结论虎杖苷对缺血受损心肌具有保护作用,其作用与降低大鼠胆固醇含量,改善高脂血症脂代谢紊乱有关。     

山楂叶总黄酮对高脂血症大鼠血清SOD、MDA及PON1的影响

目的:探讨山楂叶总黄酮(hawthorn leaves flavonoids,HLF)对高脂血症大鼠抗氧化作用的影响及与PON1活性的关系。方法:采用维生素D3加脂肪乳剂造成大鼠高脂血症模型,并检测血清超氧化物歧化酶(SOD)、丙二醛(MDA)及对氧磷酶(PON1)含量。结果:1.HLF可明显降低血清总胆固醇(TC)、甘油三脂(TG)和低密度脂蛋白胆固醇(LDL-C)含量,提高高密度脂蛋白胆固醇(HDL-C)/TC比值。2.HLF可增强SOD及PON1活性,抑制高脂饮食所升高的MDA水平。结论:HLF具有较强的抗氧化作用,其抗AS作用可能与其增加PON1表达、继而增强HDL抗氧化能力有关。     

何首乌二苯乙烯苷类提取物对高脂血症大鼠血脂代谢的影响及其抗氧化作用

目的研究何首乌二苯乙烯苷类提取物对实验性高脂血症大鼠血脂代谢的影响及抗氧化作用。方法以喂饲法建立高脂血症大鼠模型。分别灌胃给予何首乌二笨乙烯苷类提取物（12,24mg／kg）,给药4周后,测定血清血脂、载脂蛋白含量及抗氧化作用指标。结果何首乌二苯乙烯苷类提取物能明显降低血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL—c）、载脂蛋白（apoB）、脂质过氧化物（Mr）a）含量,使动脉粥样硬化指数（AI）降低,使高密度脂蛋白胆固醇（HDL—c）／TC及apoAI／apoB比值升高,并能提高高脂血症大鼠血清超过氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH—PX）活性及总抗氧化能力（T—AOC）。结论何首乌二笨乙烯苷类提取物能调节高脂血症大鼠血脂代谢及纠正自由基代谢紊乱,发挥抗动脉粥样硬化作用。     

甲基莲心碱对高脂血症模型大鼠的作用研究

目的:观察甲基莲心碱(NEF)对高脂血症模型大鼠的作用。方法:将大鼠分为正常组、模型组及NEF高、低剂量组,以高脂饲料诱发大鼠高脂血症模型,同时灌胃给予相应药物,4wk后测定绝对和相对肝重,血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白-胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和丙二醛(MDA)水平,以及谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活性。结果:与模型组比较,NEF高、低剂量组绝对和相对肝重更低,血清TC、TG、LDL-C水平显著降低,HDL-C、GSH-Px、SOD水平显著升高,血清和肝脏中MDA的含量显著降低。结论:NEF对高脂血症模型大鼠血脂具有显著的抑制作用,同时能增强机体抗氧化作用和减轻脂质过氧化。     

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.