远志醇提物对抑郁症模型小鼠的保护作用研究

目的:研究远志醇提物对抑郁症模型小鼠的保护作用。方法:通过小鼠悬尾实验、强迫游泳实验、慢性不可预知性应激+开场实验分析远志醇提物的抗抑郁作用。各小实验中雄性小鼠均分为模型对照(等容生理盐水)、氯米帕明(20mg·kg-1)和远志醇提物高、中、低剂量(10、5、2.5g·kg-1)组。结果:高、中、低剂量远志醇提物均可缩短抑郁症模型小鼠悬尾不动时间、游泳不动时间和增加移动格数。结论:远志醇提物对模型小鼠抑郁症状态有一定的改善作用。     

越鞠丸及各单味药醇提物对小鼠的抗抑郁作用研究

目的:探讨越鞠丸全方及各单味药(香附、川芎、栀子、苍术、神曲)醇提物的抗抑郁活性。方法:采用小鼠悬尾和强迫小鼠游泳实验2种行为绝望法复制小鼠抑郁模型,对越鞠丸全方及各单味药分别进行抗抑郁活性研究。结果:除神曲外,越鞠丸全方及各单味药醇提物均能不同程度地缩短小鼠悬尾不动时间和小鼠强迫游泳不动时间,具有抗抑郁样活性;越鞠丸全方醇提物、苍术和川芎可显著缩短小鼠悬尾不动时间和游泳不动时间。结论:越鞠丸全方及香附、苍术、川芎、栀子醇提物均有不同程度的抗抑郁活性,其抗抑郁活性部位/成分可能主要存在于苍术、川芎2味药材之中。     

酸枣仁总皂苷抗抑郁作用的实验研究

目的研究酸枣仁总皂苷对行为绝望小鼠抑郁模型的影响。方法采用小鼠强迫游泳实验和悬尾实验抑郁模型,小鼠行为绝望的不动时间作为指标,考察酸枣仁总皂苷抗抑郁活性。结果酸枣仁总皂苷中、高剂量组均能减少小鼠强迫游泳和悬尾不动时间,与空白对照组比较差异有统计学意义(P<0.05,P<0.01)。结论酸枣仁总皂苷具有一定的抗抑郁作用。     

五味子醇甲对小鼠抑郁样行为的影响

目的研究中药五味子的木脂素类成分五味子醇甲(SCH)的抗抑郁作用及其机制。方法小鼠单次ig给予SCH 5,10和30 mg·kg~(-1)后1 h,采用小鼠悬尾实验和强迫游泳实验评价其抗抑郁活性;采用自发活动实验评价其对中枢兴奋性的影响;采用利血平拮抗实验和育亨宾毒性实验评价其对中枢单胺神经功能的影响。结果在行为绝望模型中,与正常对照组相比,SCH 30 mg·kg~(-1)可显著缩短小鼠悬尾和强迫游泳的不动时间(P<0.05);自发活动实验结果显示,SCH在受试剂量范围内对中枢神经系统无兴奋或抑制作用;在利血平拮抗实验中,与模型组相比,SCH 30 mg·kg~(-1)可拮抗利血平(2.5 mg·kg~(-1),ip)引起的小鼠眼睑下垂和运动不能(P<0.05),对肛温下降无显著影响;在育亨宾毒性实验中,SCH各剂量对育亨宾阈致死剂量(30 mg·kg~(-1),sc)引起的小鼠死亡率无显著影响。结论 SCH具有潜在的抗抑郁药理活性。     

拟黑多刺蚁醇提物抗抑郁作用研究

目的观察拟黑多刺蚁醇提物抗抑郁作用,并对其作用机制进行初步分析。方法拟黑多刺蚁醇提物通过乙醇提取得到。采用悬尾试验、强迫游泳试验等行为绝望模型和利血平诱导的抑郁模型观察拟黑多刺蚁醇提物抗抑郁作用。结果拟黑多刺蚁醇提物8、4 g·kg-1剂量组均能明显缩短小鼠在TST和FST的悬尾不动时间和游泳不动时间(P<0.05);拟黑多刺蚁醇提物8 g·kg-1剂量组可提高抑郁症大鼠体温和糖水摄取量(P<0.05);拟黑多刺蚁醇提物8、2 g·kg-1剂量组可拮抗利血平大鼠眼睑下垂,减少运动不能时间(P<0.05,P<0.01);拟黑多刺蚁醇提物8 g·kg-1可明显提高抑郁症大鼠血清、海马组织、大脑皮层的5-羟色胺、去甲肾上腺素水平及超氧化物歧化酶的活性(P<0.05);拟黑多刺蚁醇提物对所述正常组各指标无影响。结论拟黑多刺蚁醇提物具有明显的抗抑郁作用,可能通过对神经递质代谢及对神经细胞抗氧化作用的调节来实现。     

绿萼梅提取物对小鼠的抗抑郁作用

目的：观察绿萼梅提取物对小鼠的抗抑郁作用。方法采用悬尾实验（ TFT）、强迫游泳（ FST）等体内药效评价方法观察绿萼梅醇提取物和水提取物对抑郁模型小鼠的治疗作用。结果绿萼梅醇提物能明显缩短小鼠悬尾和强迫游泳不动时间（ P＜0．05）,且对自主活动无影响（ P＞0．05）;而水提物对小鼠悬尾和强迫游泳不动时间无显著影响（ P＞0．05）。结论绿萼梅乙醇提取物具有抗小鼠抑郁作用。     

隐丹参酮对小鼠抑郁样行为的影响

目的 观察隐丹参酮的抗抑郁作用.方法 KM小鼠随机分为正常对照组、隐丹参酮低(10 mg·kg-1)、中(20 mg·kg-1)、高(30 mg·kg-1)剂量组及阳性药对照药组.采用小鼠悬尾实验、强迫游泳实验、利血平拮抗实验、5-HTP增强实验,考察隐丹参酮的抗抑郁作用.结果 隐丹参酮能够显著缩短悬尾和强迫游泳实验小...     

知母皂苷B-Ⅱ抗抑郁作用及其机制研究

目的研究知母皂苷B-Ⅱ抗抑郁的作用,并初步探讨其作用机制。方法采用小鼠悬尾实验、小鼠强迫游泳实验、开野实验;阿朴吗啡致小鼠刻板行为实验;抑制单胺（去甲肾上腺素NE和多巴胺DA）重摄取实验;育亨宾毒性增强实验;以及5-羟色胺酸（5-HTP）致甩头作用等动物模型来考察知母皂苷B-Ⅱ抗抑郁作用及其可能的机制。分别以小鼠不动时间、自主活动数、刻板行为评分、死亡率作为评价指标。结果在小鼠悬尾实验中,知母皂苷B一Ⅱ（100、150mg／kg）能够明显缩短小鼠的不动时间;在小鼠强迫游泳实验中,知母皂苷B-Ⅱ（50、100、150mg／kg）均能够明显缩短小鼠的不动时间;对开野实验中小鼠的自主活动次数无明显影响。在抑制NE和DA重摄取实验中,知母皂苷B-Ⅱ高剂量（150mg／kg）显著增加多巴胺（DA）致小鼠死亡作用,但对去甲肾上腺素（NE）重摄取抑制作用不明显。阿朴吗啡致小鼠刻板运动实验显示,知母皂苷B-Ⅱ（100、150mg／kg）对注射阿朴吗啡后的小鼠刻板运动有显著增强作用,差异具有显著意义（P〈0．05）;具有增加5-羟色胺酸（5-HTP）致甩头作用;知母皂苷B-Ⅱ不具有增加育亨宾毒性的作用。结论知母皂苷B-Ⅱ有抗抑郁活性,其作用机制可能与增强脑内5-HT、DA神经系统作用有关。     

人参总皂苷对小鼠的抗抑郁作用

目的：初步探讨人参总皂苷对小鼠的抗抑郁作用。方法：选取健康雄性昆明种小鼠,随机分为5组,空白对照组、阳性药组、人参总皂苷125、250、500 mg.kg^-1剂量组。通过小鼠自主活动实验、小鼠强迫游泳实验和小鼠悬尾实验,观察人参总皂苷对小鼠抗抑郁作用的影响。结果：各给药组小鼠自主活动行为与空白对照组比较均无明显差异;人参总皂苷125、250、500 mg.kg-1均可以显著缩短小鼠强迫游泳及小鼠悬尾不动时间。结论：实验结果表明人参总皂苷在小鼠＂行为绝望＂模型中有一定的抗抑郁作用。     

柴胡皂苷对石菖蒲醇沉液抗抑郁作用的影响

目的观察石菖蒲醇沉液的抗抑郁作用及柴胡皂苷对其抗抑郁作用的影响。方法选用小鼠尾悬挂试验、大鼠强迫游泳试验和小鼠5-HTP增强试验分别测定小鼠悬尾不动时间、大鼠强迫游泳不动时间和小鼠甩头次数。结果在小鼠尾悬挂试验和大鼠强迫游泳试验中,石菖蒲醇沉液能使小鼠和大鼠的不动时间显著缩短,柴胡皂苷可加强石菖蒲醇沉液缩短小鼠、大鼠不动时间的作用;在小鼠5-HTP增强甩头试验中,较大剂量（10g／kg）的石菖蒲醇沉液能增强小鼠甩头反应,柴胡皂苷有加强石菖蒲醇沉液增强小鼠甩头反应的作用。结论石菖蒲醇沉液有抗抑郁作用,柴胡皂苷可加强石菖蒲醇沉液的抗抑郁作用。     

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.