抗抑郁剂吗氯贝胺的行为效应

加强5-羟色氨酸及β-苯乙胺致小鼠刻板行为实验表明, ig吗氯贝胺(Moc)对单胺氧化酶(MAO)- A 的选择性抑制作用 (ED₅₀=0.33 mg·kg^-1, 2 h) 较MAO-B (ED₅₀=12.7 mg·kg^-1, 2 h) 强约39倍. 24 h内ip Moc 300 mg·kg^-1有一定镇静作用. 对运动系统无明显影响，不引起记忆及定向障碍. Moc 600 mg·kg^-1不能对抗氧化震颤素引起的小鼠震颤和分泌增加. Moc的LD₅₀为小鼠: 1.3-1.5 g·kg^-1 ig; 198-199 mg·kg^-1 iv; 大鼠: 541-562 mg·kg^-1 ip. Moc 剂量依赖地对抗利血平引起的小鼠和大鼠睑下垂, 活动减少和体温降低；使慢性应激刺激引起的小鼠活动性增高及穿箱逃避电击反应失败率增高得到恢复，提示其抗抑郁作用.     

灵芝孢子多糖抗移植性肿瘤实验研究

目的 研究灵芝孢子多糖的抗癌作用。方法 采用小鼠抗移植性肿瘤实验方法。结果 灵芝孢子多糖分别以150 mg·kg^-1、300 mg·kg^-1和600 mg·kg^-1剂量连续12天灌胃给药,对小鼠移植性肝癌Heps的抑瘤率为53.77%～65.25%;连续8天灌胃给药,对小鼠移植性肉瘤S₁₈₀的抑瘤率为50.39%～55.04%,皆呈良好的抑瘤作用。灵芝孢子多糖可分别提高Heps和S₁₈₀荷瘤小鼠的脾指数和胸腺指数。结论 灵芝孢子多糖有良好的抑瘤作用,并可增强Heps和S₁₈₀荷瘤小鼠的非特异性免疫功能。     

胞嘧啶脱氨酶基因与前体药物5-氟胞嘧啶联合应用对人乳腺癌裸鼠模型的实验治疗

探讨胞嘧啶脱氨酶（CD）基因与前体药物5-氟胞嘧啶（5-FC）对人乳腺癌裸鼠移植瘤的抗肿瘤作用. 应用细胞克隆形成实验及裸鼠移植瘤模型研究CD/5-FC体系的抗肿瘤作用. 5-FC 0.5和1.0 g·L^-1对转基因人乳腺癌细胞的克隆形成抑制率分别为90%和95%,显著高于未转基因的人乳腺癌细胞;5-FC (0.5 g·kg^-1·d^-1 ip, 14 d)治疗组的转基因人乳腺癌裸鼠移植瘤的瘤重和生长速度均显著低于未转基因的移植瘤. 结果表明CD/5-FC体系对人乳腺癌裸鼠移植瘤有显著的的抗肿瘤作用.     

姜百片对大鼠醋酸损伤胃溃疡模型的干预作用

目的 研究一种由高良姜、香附、百合和乌药提取物制成的复方中药姜百片对大鼠醋酸损伤胃溃疡模型胃黏膜的保护作用。方法 采用醋酸注射法制作大鼠醋酸胃溃疡模型,将动物分为模型组、雷尼替丁阳性对照组(0.108 g·kg^-1·d^-1)、姜百片高(2.16 g·kg^-1·d^-1)、中(1.08 g·kg^-1·d^-1)、低(0.54 g·kg^-1·d^-1)剂量组,连续口服给药10 d后处死并解剖大鼠,测量胃黏膜溃疡面的长短径(L和H),按照公式S=πLH/4计算溃疡面积,用试剂盒测定损伤部位表皮生长因子(EGF)和血管内皮生长因子(VEGF)的水平。结果 与模型组相比,该复方中药的高(2.16 g·kg^-1·d^-1)、中(1.08 g·kg^-1·d^-1)、低(0.54 g·kg^-1·d^-1)剂量可以显著减小醋酸损伤大鼠的溃疡面积(P<0.05),并可显著提高醋酸损伤部位组织的表皮生长因子(EGF)(P<0.05)和血管内皮生长因子(VEGF)(P<0.05)的水平。结论 姜百片具有抗醋酸损伤型胃溃疡的作用,其作用机制可能与提高组织的EGF和VEGF水平等有关。     

丁基苯酞对正常及局部脑缺血大鼠纹状体脑血流影响

应用氢清除法连续测定大鼠一侧纹状体脑血流量(rCBF), 并观察丁基苯酞(NBP)对其影响. 结果表明, NBP 40或80 mg·kg^-1 ig均能显著增加大脑中动脉阻断后纹状体的rCBF(与溶剂对照组相比P<0.01), 作用持续3 h. 此外, 5-20 mg·kg^-1 ig时, 也可增加正常大鼠纹状体脑血流, 各剂量组NBP对平均动脉压均无明显影响; 尼莫地平(Nim)0.5 mg·kg^-1 ip也能明显增加纹状体脑血流, 同时轻度降低动脉平均压, 其增加脑血流作用与NBP 5 mg·kg^-1的作用相当. 提示NBP不仅能增加正常大鼠纹状体的脑血流, 还能增加大脑中动脉阻断后纹状体的血流量, 其抗脑缺血作用可能与该作用有关.     

沙利度胺与5-氟尿嘧啶联合使用的抗肿瘤作用

目的 :考察沙利度胺与 5 氟尿嘧啶 (5 Fluorouracil,5 FU)联合使用的抗肿瘤作用。方法 :(1)沙利度胺的抗肿瘤作用 :小鼠EAC细胞接种于昆明种小鼠前肢腋下皮下 ,建立小鼠EAC实体瘤模型 ,随机分为空白对照组 ,沙利度胺组 (5 0 ,10 0 ,2 0 0mg·kg-1,ig) ,5 FU(2 0mg·kg-1,ip)。连续给药 14d ,第 15天解剖 ,取瘤称重。 (2 )沙利度胺与 5 FU联合使用的抗肿瘤作用 :制备小鼠EAC实体瘤模型 ,随机分为空白对照组 ,沙利度胺组 (5 0mg·kg-1,ig) ,5 FU组 (5 ,10 ,2 0mg·kg-1,ip) ,沙利度胺 (5 0mg·kg-1,ig)合用 5 FU组 (5 ,10mg·kg-1,ip)。沙利度胺均上午ig ,5 FU均下午ip。连续给药 14d ,第 15天解剖 ,取瘤称重。结果 :(1)单独使用沙利度胺 (5 0 ,10 0 ,2 0 0mg·kg-1,ig)抗肿瘤作用不明显 ,抑瘤率分别为 13.8% ,2 1.4 % ,2 4 .2 % ;(2 )沙利度胺 (5 0mg·kg-1,ig)与 5 FU(10mg·kg-1,ip)联合使用的抑瘤率为 6 3.3%。结论 :沙利度胺与 5 FU联合使用抗肿瘤作用增强。     

五福饮对荷瘤小鼠抑瘤率和免疫调节作用的影响

目的 观察五福饮对荷S180移植瘤小鼠免疫功能的影响及抑瘤作用。方法 荷瘤小鼠随机分为模型组、环磷酰胺对照组(80 mg·kg^-1),五福饮低、中、高剂量组(分别含生药5.25,10.5,21.0 g·kg^-1,相当于人体临床用量的10,20和40倍)及正常对照组。结果 与模型组比较,五福饮高、中2个剂量组均可明显提高荷瘤小鼠ConA诱导的脾淋巴细胞转化、小鼠NK细胞活性和血清IFN-γ、TNF-α水平,差异均有统计学意义(P<0.05)。五福饮各组对S180移植瘤抑制率为11%~16%,但与模型组比较无明显差异(P＞0.05)。结论 五福饮对S180移植瘤的抑制作用不显著,但可增强荷S180移植瘤小鼠的免疫功能。     

N-乙酰半胱氨酸对化疗所致骨髓抑制的改善作用

目的 探讨N-乙酰半胱氨酸(NAC)对化疗所致骨髓抑制的改善作用。方法 1 体内实验:将C57BL/6j小鼠随机分为正常对照组、环磷酰胺(Cy)所致骨髓抑制模型对照组(ip给予生理盐水)以及模型＋NAC 30,90和270 mg·kg^-1组,每天1次,连续10 d。给药第4天一次性ip给予Cy 380 mg·kg^-1制备骨髓抑制小鼠模型。造模后第1,2,3,4和7天,鼠尾静脉取血20 μl检测外周血像,同时取一侧股骨骨髓,检测骨髓单个核细胞(BM-MNC)数目;造模后第1天,检测BM-MNC凋亡和细胞内活性氧(ROS)水平。2 体外实验:C57BL/6j小鼠一次性ip给予Cy 380 mg·kg^-1后第3天,取BM-MNC进行造血祖细胞培养,在培养体系中加入NAC 0.01, 0.1, 1和5 mmol·L^-1,于第7~12天检测造血祖细胞粒红巨噬巨核系集落形成单位(CFU-Mix)、粒细胞巨噬细胞集落形成单位(CFU-GM)和红系爆式形成单位(BFU-E)数目,观察NAC体外对骨髓抑制模型小鼠造血祖细胞增殖分化的影响。结果 1 体内实验:与正常对照组相比,ip给予Cy后第1~4天,模型组BM-MNC和外周血白细胞(WBC)数目显著下降,造模后第7天仍未恢复正常。与模型组相比,造模第2天,NAC 270 mg·kg^-1组WBC数目降低;其余各时间点,NAC各治疗组的WBC数目无明显差异,NAC 30和90 mg·kg^-1组WBC最低值于造模后第4天出现。与模型组比较,造模后第1天NAC 30和90 mg·kg^-1组ROS水平降低,BM-MNC凋亡率无明显差异; 造模后第1~2天BM-MNC明显增加。2 体外实验:与正常对照组相比,模型组造血祖细胞CFU-Mix,CFU-GM和BFU-E数目均明显降低;与模型组比较,NAC 0.1 mmol·L^-1能够增加骨髓抑制小鼠骨髓造血祖细胞CFU-GM和BFU-E数目,但NAC 5 mmol·L^-1减少模型小鼠CFU-GM,BFU-E和CFU-Mix数目。结论 NAC通过降低ROS水平对化疗所致骨髓抑制有一定的改善作用。     

全肠外营养治疗婴儿肺炎并发胃肠功能障碍25例

目的 观察全肠外营养支持治疗婴儿肺炎并发胃肠功能障碍的疗效。方法 将50例肺炎并发胃肠功能障碍婴儿随机分为治疗组和对照组各25例。治疗组给予全肠外营养支持治疗和禁食、胃肠减压、抗炎及其他对症治疗。全肠外营养液的计算方法为：① 计算每天的总补液量及所需总能量，减去给药治疗所需的液体体积及能量后计算全肠外营养液的体积及能量；② 8.5%复方氨基酸注射液从0.5 g·kg^-1·d^-1起，每天增加0.5 g·kg^-1(但总用量应≤25 g·kg^-1·d^-1)；③ 20%脂肪乳从0.5 g·kg^-1·d^-1起，每天增加0.5 g·kg^-1(总用量应≤ 40 g·kg^-1·d^-1)；④ 脂溶性维生素注射液1 mL·kg^-1·d^-1；⑤ 水溶性维生素注射液1 mL·kg^-1·d^-1； ⑥ 每输入100 mL液体补充10%氯化钠注射液2～3 mL， 10%氯化钾注射液1～2 mL；⑦ 输入50%葡萄糖注射液的体积＝所有不含葡萄糖的液体体积的1/4，剩余液体以10%葡萄糖注射液补足，使营养液中葡萄糖的浓度为10%。以上各药物混匀后静脉输入。对照组以相同方法计算总液体量及能量，由周围静脉分别输注氨基酸(占总能量的15%)、脂肪乳(占总能量的30%)、葡萄糖(占总能量的55%)、维生素等营养物质。结果 治疗组治愈19例(占76.0%)，好转5例(占20.0%)，总有效率96.0%；对照组治愈15例(占60.0%)，好转5例(占20.0%)，总有效率80.0%；治疗组疗效明显高于对照组( P＜0.05)，且并发症少。结论 全肠外营养支持治疗婴儿肺炎并发胃肠功能障碍安全有效，有利于患儿病情好转，值得临床推广使用。     

烟碱和槟榔碱对大鼠颌下腺肌醇含量的影响

急性实验中，间隔5 min反复ip N受体激动剂烟碱0.5, 1.0, 1.0, 2.0, 2.0 mg·kg^-1可显著提高大鼠颌下腺中肌醇含量，并为N受体拮抗剂美加明1.0 mg·kg^-1对抗，为肌醇磷酸酶抑制剂氯化锂69.4 mg·kg^-1 ip翻转；一次性ip M受体激动剂槟榔碱200 mg·kg^-1也可显著提高颌下腺肌醇含量，并为M受体拮抗剂阿托品2.0 mg·kg^-1对抗；反复注射烟碱后，再ip不影响肌醇含量的槟榔碱50 mg·kg^-1，两者产生协同效应，进一步提高肌醇含量. 慢性实验中，每日2次sc烟碱2.0-5.0 mg·kg^-1或槟榔碱2.0-10.0 mg·kg^-1 14 d后，均可使大鼠颌下腺中肌醇含量显著降低.     

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.     

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.