左旋千金藤立定对大鼠血清中催乳素水平的影响(英文)

目的:观察左旋千金藤立定(SPD)对血清催乳素(PRL)水平的影响,研究SPD的药理作用。方法:成熟♀鼠ip多巴胺受体激动剂、拮抗剂或SPD后断头取血,然后用放射免疫法测定血清中的催乳素水平。结果:SPD引起血清PRL水平迅速而显著的增加,效应持续约1h,具有剂量依赖性。SPD的半数有效剂量为3.7mg·kg~(-1)(95％可信限为2.6—4.3mg·kg~(-1))。剂量为20mg·kg~(-1)时产 生最大效应,使血清PRL水平达到448±64μg·L~(-1),0.2mg·kg~(-1)则无效。对于多巴胺受体激动剂培高利特(pergolide)引起的PRL水平低下,SPD5mg·kg~(-1)有部分对抗作用,10mg·kg~(-1)能够完全对抗。结论:SPD是D_2多巴胺受体拮抗剂。     

增乳方对左旋多巴诱导的哺乳大鼠低泌乳素血症的逆转作用

目的 :研究增乳方 (CLD)对左旋多巴诱导的低泌乳素血症哺乳大鼠乳汁分泌的促进作用。方法 :采用左旋多巴 (L Dopa)诱导建立哺乳大鼠乳汁分泌低下模型 ;大鼠ig给予CLD ,观察不同剂量 (3、6、2 0g·kg-1·d-1)CLD对哺乳期大鼠的仔鼠体重以及母鼠血清泌乳素 (PRL)和乳腺组织学的影响。结果 :大鼠给予CLD 3、6、2 0g·kg-1·d-1,血清PRL值显著高于模型组 (P <0 .0 5 ,P <0 .0 1) ,呈量 效关系 ;CLD可明显增加母鼠泌乳量 ,促进仔鼠体重的增长 (P <0 .0 5 )并促进母鼠乳腺的发育。结论 :CLD对L Dopa诱导的哺乳大鼠低泌乳素血症具有逆转作用 ,且促进乳汁的分泌     

培高利特对黑质多巴胺神经元放电活动的激动作用(英文)

目的:研究D_2受体激动剂培高利特(pergolide,Per)对大鼠黑质多巴胺(DA)神经元放电活动的影响,并与溴隐亭(bromocriptine,Bro)作比较,同时验证Per在整体动物有无D_1激动剂性质.方法:胞外单细胞电活动记录技术. 结果:二个药物均能抑制敏感及不敏感的DA神经元自发放电活动.Per的ID_(50)值为11.9μg kg~-1),而Bro为7.8 mg kg~(-1),Per比后者强很多.选择性D_2受体拮抗剂螺哌隆(spiperone,0.25 mg kg~(-1))或者选择性D_1受体拮抗剂Sch-23390(1—2 mg kg~(-1))可以减弱放电抑制.然而Bro引起的放电抑制并不都能为spiperone所减弱.结论:Per在整体动物有很强的D_2受体激动剂作用,比Bro强650倍.也有弱的D_1受体激动剂的性质.     

索布佐生和阿霉素对小鼠白血病P388的协同作用

目的:研究索布佐生(Sob)与阿霉素(Dox)联合应用的抑瘤作用以及Sob对Dox诱导的心脏毒性的影响。方法:DBA/2小鼠接种P388细胞,次日起iv Dox 2mg·kg~(-1)·d~(-1)×3d及4mg·kg~(-1)·d~(-1)×1 d,ig Sob 20mg·kg~(-1)·d~(-1)×7d及40mg·kg~(-1)·d~(-1)×7d,配对联用。统计各组的生命延长率(ILS);电镜观察荷瘤鼠垂死前的心肌毒性表现。结果:联合用药组的ILS分别为48.7％,57.3％,59.0％和62.4％,是Sob和Dox单药应用ILS之和的130％—190％,荷瘤鼠心肌细胞的超微结构损伤较单用Dox组明显减轻。结论:Sob与Dox联用对小鼠白血病P388有显著的抑瘤协同作用;Sob能降低Dox所致的心肌毒性。     

2种小鼠模型用于研究丹参酮ⅡA预防肿瘤细胞肺部的转移

目的研究丹参酮ⅡA用于预防肿瘤细胞在小鼠肺部转移的预防效果。方法高剂量组100 mg·kg~(-1)·d~(-1),中剂量组50 mg·kg~(-1)·d~(-1),低剂量组5 mg·kg~(-1)·d~(-1)及对照组,每组10只,BALB/c小鼠提前3 d灌胃给药,每只小鼠采用尾静脉注射4T1乳腺癌细胞1×10~5和乳房垫注射4T1乳腺癌细胞1×10~7,连续灌胃28 d,解剖观察并记录小鼠肺部肿瘤细胞转移情况。结果小鼠尾静脉注射4T1模型中,对照组小鼠的肺部结节数(6±2)个,低剂量组肺结节数(2±0.5)个,中剂量组肺结节数(2±0.3)个,高剂量组肺结节数(2±0.2)个,治疗组和对照组比较分析存在显著性差异。小鼠乳房垫注射4T1模型中,对照组小鼠的肺部结节数(18±4)个,低剂量组肺结节数(14±3)个,中剂量组肺结节数(13±2)个,高剂量组肺结节数(10±1)个,治疗组中高剂量组和对照组比较分析存在显著性差异。结论在小鼠尾静脉注射4T1模型和乳房垫注射4T1模型中,表明丹参酮ⅡA具有预防肿瘤细胞转移的药效。     

云芝多糖B对大鼠单核细胞趋化蛋白—1基因表达的影响

目的:探究野生云芝多糖水溶性新组分CVPS-B对大鼠脾细胞单核细胞趋化蛋白-1(MCP-1)基因表达的影响.方法:以β-actin为内标准物,用逆转录聚合酶链式反应(RT-PCR)检测CVPS-B分别对正常情况下以及脂多糖(LPS)诱导下大鼠脾细胞MCP-I基因表达的影响,并对RT-PCR产物进行测序,以证实其特异性.结果:(1)正常情况下大鼠脾细胞MCP-1 mRNA的表达(MCP-1/β-actin的比值)生理盐水对照组为1.4±0.3;CVPS-B三个剂量组(10、30和50mg·kg~(-1)·d~(-1),ip,连续4d)分别为:1.6±0.4、1.7±0.5和1.5±0.4,后三组与对照组无显著差异(P>0.05);(2)大鼠腹腔给药LPS(10μg·kg~(-1)可使脾细胞MCP-1 mRNA的表达增加114％.(3)CVPS-B4个剂量组(5、10、30和50mg·kg~(-1)·d~(-1),ip,连续4d)可使LPS(10μg·kg~(-1),ip)诱导的脾细胞MCP-1 mRNA的表达分别减低51％,70％,84％和99％(n=6).结论:CVPS-B可预防性抑制LPS对大鼠脾细胞MCP-1基因表达的诱导作用,且呈剂量依赖性,但对正常情况下大鼠脾细胞MCP-1 mRNA的表达则无明显影响.     

氯代斯阔任对多巴胺受体的作用

目的:比较四氢原小檗碱同类物(THPB)和氢化苄基-四氢异喹啉类(HBTI)两类化合物对DA受体的作用强度,从而找出对DA受体作用更有效的化合物。方法:用小牛纹状体膜蛋白对D_1和D_2受体进行放射受体结合分析并进行大鼠行为实验。结果:(±)12-氯代斯阔任(CSL)对D_1和D_2受体的亲和力分别为13和51nmol·L~(-1),与先导化合物左旋千金藤立定[(-)stepholidine,SPD]在同一水平,动物行为实验表明它对DA受体有阻滞作用,但在超敏条件下,出现激动作用,这些特点与SPD的作用类似。结论:CSL是目前THPB中对DA受体作用最强者,与SPD类似是对DA受体阻滞剂兼有激动作用。     

丹参素对糖皮质激素诱导骨丢失大鼠胫骨近端骨密度和骨微结构的影响

目的探讨丹参素对糖皮质激素诱导骨丢失大鼠胫骨近端骨密度和骨微结构的影响。方法 60只7月龄SPF级♀SD大鼠按体质量随机分为6组,每组10只:空白对照组(生理盐水:5 mL·kg~(-1)·d~(-1))、糖皮质激素模型组(醋酸泼尼松:6 mg·kg~(-1)·d~(-1))、糖皮质激素+丹参素低剂量组(12.5 mg·kg~(-1)·d~(-1))、糖皮质激素+丹参素中剂量组(25mg·kg~(-1)·d~(-1))、糖皮质激素+丹参素高剂量组(50 mg·kg~(-1)·d~(-1)),糖皮质激素+(阳性对照药)骨化三醇组(0.045μg·kg~(-1)·d~(-1))。采用醋酸泼尼松连续灌胃14周建立大鼠骨丢失模型,同时采用丹参素和骨化三醇灌胃给药进行干预。实验结束后,取左侧胫骨近端进行Micro-CT扫描并分别对皮质骨和松质骨进行三维重建,观察骨微结构并检测骨密度等相关参数。结果糖皮质激素可引起大鼠胫骨近端骨密度下降,骨微结构异常。给予中剂量丹参素和骨化三醇均可提高骨密度并改善骨微结构,且二者效果相当;高剂量丹参素对骨微结构有一定程度的改善,但对骨密度无明显改变;低剂量丹参素对骨密度和骨微结构均无明显改善。结论丹参素(25 mg·kg~(-1)·d~(-1))灌胃给药可预防糖皮质激素引起的大鼠胫骨近端骨密度下降和骨微结构异常。     

Therapeutic role and its mechanism of gypenosides on delayed healing of experimental gastric ulcer induced by NCTC11637 strain HP in rats

AIM: To investigate the adverse action of Helicobacter pylori(HP) (NCTC11637 strain ) and the therapeutic effect ofGypenosides (GP) isolated from Gynostemma pentaphyllum onulcer healing in rats. METHODS: After ulcer induction byacetic acid in the stomach, rats were divided into 4 groups. Theywere eithe given ig with distilled water or with CagA ( ) andVacA ( ) NCTC1163HP (1 mg·kg~(-1)·d~(-1) ) alone or togetherwith GP (15 or 45 mg·kg~(-1)·d~(-1) ) for 9 d. The changes of     

甲苯达唑对小鼠细粒棘球蚴囊壁与囊液的游离氨基酸成分的影响(英文)

感染11个月的小鼠细粒棘球蚴囊壁与囊液分别含有18种和23种游离氨基酸。除牛磺酸外,囊液中的游离氨基酸含量均较囊壁的为高。用甲苯达唑25mg·kg~(-1)·d~(-1)×14d与50mg·kg~(-1)·d~(-1)×7d ig治疗小鼠后,囊壁与囊液的丙氨酸、缬氨酸、赖氨酸及牛磺酸的含量均明显增高,以囊壁的丙氨酸的增高为最显著。     

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.     

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.     

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.