苏郁胶囊对抑郁模型大鼠血浆ACTH、皮质醇和免疫功能的影响

目的:研究苏郁胶囊对慢性应激抑郁模型大鼠的血浆促肾上腺皮质激素(ACTH)、皮质醇及免疫功能的影响。方法:将72只成年SD雄性大鼠随机分为正常组、模型组、苏郁胶囊高、中、低剂量组(22．8,11．4,5．7 g·kg-1)及氯米帕明组(0．02 g·kg-1)。采用长期不可预见性中等强度应激结合孤养造成大鼠抑郁模型,造模同时各组ig给药,正常组及模型组给予等量的生理氯化钠溶液,qd,共21 d。测定各组大鼠体重变化、糖水消耗量及强迫游泳不动时间;采用放射免疫方法检测大鼠血浆ACTH和皮质醇含量;测定各组大鼠的淋巴细胞增殖及自然杀伤细胞(NK)活性。结果:与模型组比较,苏郁胶囊高剂量组的体重增长明显加快(P<0．05),游泳不动时间明显缩短(P<0．05);苏郁胶囊3个剂量组的总液体消耗量及糖水消耗量均明显增加(P<0．01或P<0．05);高、中剂量组血浆中ACTH和皮质醇含量均明显降低(P<0．01或P<0．05),脾淋巴细胞增殖和NK细胞杀伤活性显著增加(P<0．01或P<0．05)。结论:苏郁胶囊具有抗抑郁作用,其作用机制可能与抑制神经内分泌异常改变及促进机体的免疫机能相关。     

郁可欣胶囊的抗抑郁作用研究

目的：研究郁可欣胶囊的抗抑郁作用。方法：选择小鼠强迫游泳、悬尾应激及利血平所致眼睑下垂小鼠抑郁模型，用郁可欣胶囊对其进行治疗观察。结果：郁可欣胶囊可以对抗小鼠因强迫悬尾及强迫游泳造成的抑郁症状，并可对抗利血平所致的小鼠眼睑下垂。结论：郁可欣胶囊能明显改善行为绝望动物模型的抑郁症状。     

1,3,7,9-四甲基尿酸抗抑郁作用的实验研究

目的探讨1,3,7,9-四甲基尿酸(theacrine,TC)的抗抑郁作用。方法采用悬尾实验、强迫游泳实验、自主活动实验、育亨宾(yohimbine)毒性实验、利血平(reserpine)实验以及5-羟色胺酸(5-HTP)诱导小鼠甩头行为等动物模型(各组剂量分别为3、10及30mg·kg-1,bid,连续7d灌胃给药)来评价TC的抗实验性抑郁效果及其可能的作用机制。结果与空白对照组相比,TC能明显缩短小鼠悬尾不动时间(P<0.01)及增加强迫游泳小鼠拨动转轮旋转次数(P<0.05),且对自主活动无影响。TC可一定程度上增强yohim-bine诱发实验动物死亡率,增强5-HTP导致的甩头行为(P<0.01)。此外,TC也具有明显地改善reserpine引起的小鼠体温下降(P<0.01),运动不能(P<0.05)和眼脸下垂(P<0.01)的作用。结论TC在多种抑郁模型上显示一定的药理活性,这些作用可能与影响单胺类神经递质有关。     

还少胶囊抗抑郁作用的实验研究

目的：测定还少胶囊对抑郁小鼠行为学、生化指标的影响，证实还少胶囊具有抗抑郁疗效。方法：开场实验测定还少胶囊对正常小鼠自主活动能力的影响。建立小鼠悬尾、强迫游泳模型，测定还少胶囊对抑郁小鼠行为学、脑部单胺类神经递质、肝脏丙二醛和超氧化物歧化酶含量的影响。结果：经过7天给药，小鼠自主活动能力无显著改变。悬尾、强迫游泳实验中动物不动时间均显著减少。与正常组对比，还少胶囊正常组大部分生化指标改变不显著；与模型组对比，还少胶囊模型组能显著增加中枢五羟色胺（5-HT）和去甲肾上腺素（NE）含量，减少肝脏丙二醛（MDA）和超氧化物歧化酶（SOD）含量，且中、低剂量时效果更好，优于氟西汀。结论：还少胶囊具有良好抗抑郁作用，对正常动物相关生化指标影响很小，且无中枢神经兴奋作用。     

白芍解郁颗粒对小鼠抑郁模型的影响

目的研究白芍解郁颗粒对小鼠抑郁模型的影响. 方法选择小鼠强迫游泳、悬尾应激及利血平所致眼睑下垂小鼠抑郁模型,用白芍解郁颗粒对其进行治疗观察.结果白芍解郁颗粒可以对抗小鼠因强迫悬尾及强迫游泳造成的抑郁症状,并可对抗因利血平所致小鼠眼睑下垂和体温下降.结论白芍解郁颗粒能明显改善抑郁动物模型的抑郁症状.     

醒神开郁方抗抑郁作用的实验研究

目的：研究醒神开郁方的抗抑郁作用及其可能的作用机制。方法：采用小鼠悬尾、强迫游泳实验观察小鼠悬尾、游泳不动时间;自主活动实验测定小鼠自主活动次数;利血平诱导小鼠体温下降实验考察小鼠肛温、眼睑下垂度以及脑内单胺类神经递质含量等指标。采用SPSS 13.0软件对上述观察指标进行统计分析。结果：醒神开郁方对小鼠自主活动行为无显著影响;在小鼠悬尾和强迫游泳实验中,醒神开郁方低、中、高剂量组可明显缩短小鼠悬尾和强迫游泳不动时间（P〈0.05,P〈0.01,P〈0.01）。利血平诱导小鼠体温下降实验中,与模型组比较,醒神开郁方中、高剂量组可显著拮抗利血平所致小鼠的体温下降和眼睑下垂（P〈0.05,P〈0.01）;与模型组比较,醒神开郁方中、高剂量组均能显著增加小鼠脑组织内NE、5-HT含量（P〈0.01）以及DA含量（P〈0.05,P〈0.01）。结论：醒神开郁方具有显著的抗抑郁作用,其作用机制与增强脑组织内NE、5-HT、DA调节神经系统作用有关,且醒神开郁方无中枢兴奋作用。     

解郁汤对慢性应激抑郁模型小鼠的抗抑郁作用及机制研究

目的：探讨解郁汤的抗抑郁作用及可能机制。方法：以慢性轻度不可预见性应激方法建立小鼠抑郁症模型,以糖水消耗、悬尾实验、强迫游泳实验、开野实验进行行为学评分,并通过UPLC—T—QMS系统检测其脑内单胺类神经递质的含量,观察模型小鼠给药前后的变化。通过免疫组化检测小鼠海马区BDNF以及5-Brdu表达。结果：与空白组相比．模型组的小鼠蔗糖水消耗量明显下降,强迫游泳不动时间、悬尾不动时间均显著增加,交叉次数、直立次数显著减少,脑内的去甲肾上腺素、5-羟色胺、5-羟色胺吲哚乙酸含量降低（P〈0．05）。与模型组相比,解郁汤组小鼠蔗糖水消耗量显著升高,强迫游泳不动时间、悬尾不动时间均显著减少（P〈0．05）。解郁汤能显著增加大鼠脑内去甲肾上腺素、5-羟色胺、5-羟色胺吲哚乙酸含量（P〈0．05）。解郁汤能增加小鼠脑内海马区BDNF以及5-Brdu表达。结论：解郁汤具有抗抑郁作用,其作用机制可能与调节中枢单胺类神经递质的调节以及促进海马神经元再生有关。     

心脑欣胶囊对慢性抑郁大鼠的作用研究

目的:研究心脑欣胶囊对不可预知慢性应激抑郁模型大鼠抗抑郁作用及其可能的作用机制。方法:采用慢性不可预知应激刺激的方式建立大鼠慢性应激抑郁模型。通过开野、糖水偏好、强迫游泳、悬尾等实验观察心脑欣胶囊对慢性抑郁大鼠行为学的影响;观察心脑欣胶囊对慢性抑郁大鼠血清皮质酮含量和海马组织单胺氧化酶(MAO)、诱导型一氧化氮合酶(iNOS)及一氧化氮(NO)水平的影响。结果:心脑欣胶囊可明显提高慢性抑郁大鼠水平得分和垂直得分、糖水偏好程度,显著降低慢性抑郁大鼠强迫游泳、悬尾实验不动时间,显著降低慢性抑郁大鼠血清皮质酮含量,显著抑制其海马组织MAO、iNOS的活力和降低NO含量。结论:心脑欣胶囊对慢性抑郁大鼠具有明显的抗抑郁作用,其机制可能与抑制MAO、iNOS活性,降低皮质酮和NO水平,减轻海马损伤等有关。     

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。     

一种白僵菌代谢产物提取物抗实验性抑郁的研究

目的　研究一种白僵菌代谢产物提取物 (BCEF0 0 83)抗实验性抑郁的作用。方法　采用小鼠获得性绝望模型 (小鼠强迫游泳实验、小鼠悬尾实验 )及慢性不可预见性应激、孤养模型研究BCEF0 0 83抗实验性抑郁作用及可能的作用机制 ;采用紫外、荧光分光光度计法检测BCEF0 0 83对模型动物脑组织单胺氧化酶活性、单胺递质含量的影响。结果　在小鼠强迫游泳实验、小鼠悬尾实验中 ,BCEF0 0 832 5、5 0、10 0mg·kg-13个剂量组均可明显缩短小鼠的不动时间 ,且呈现一定的量效关系 ;BCEF0 0 832 5、5 0、10 0mg·kg-13个剂量组对慢性应激模型小鼠脑组织重线粒体MAO A ,B活性均有明显的抑制作用 ,且呈现一定的量效关系。BCEF0 0 832 5、5 0、10 0mg·kg-13个剂量组对慢性应激模型小鼠脑组织NE、5 HT、5 HIAA、DA的含量有不同程度的提高。结论　BCEF0 0 83具有一定的抗小鼠实验性抑郁作用 ,其机制可能与抑制动物脑组织单胺氧化酶活性、升高单胺递质含量有关。     

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.

     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.