枸骨叶提取物对高脂血症模型大鼠脂代谢及血液流变学的影响

目的:探讨枸骨叶提取物对高脂血症模型大鼠血脂调节功能及血液流变学影响,为该药物的开发和应用提供实验依据。方法:高脂饲料喂饲4周建立高脂血症大鼠模型后,随机将试验大鼠分为空白对照组、模型对照组、阳性对照组、枸骨叶提取物高剂量组(0.60 g·ml^-1)、中剂量组(0.30 g·ml^-1)、低剂量组(0.15 g·ml^-1),灌胃给药9周,分别测定各组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）、天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、超氧化物歧化酶（SOD）及丙二醛（MDA）的含量,并测定血液流变学各项指标。结果:给药9周后,与模型组比较,不同剂量枸骨叶提取物对大鼠TC、TG、LDL-C、ALT、AST、MDA、载脂蛋白B的含量均有不同程度降低,对HDL-C、SOD活性及载脂蛋白A的水平均有不同程度升高,其中以枸骨叶高剂量作用效果最显著（P<0.05,P<0.01）;不同剂量枸骨叶提取物均能不同程度地降低大鼠血浆黏度、全血黏度、红细胞聚集指数、红细胞压积,升高红细胞变形指数,且枸骨叶高剂量差异极显著（P<0.05,P<0.01）。结论:枸骨叶对高脂血症模型大鼠的血脂和血流异常具有显著调节作用,从而达到降低血脂水平的目的。     

红雪茶提取物降脂保肝作用的实验研究

目的研究红雪茶提取物(HXC)对大鼠非酒精性脂肪肝(NAFLD)的降脂保肝作用。方法采用高糖高脂饲料建立NAFLD大鼠模型,同时分别采用不同剂量的HXC(含生药0.9、2.7g.kg-1.d-1)以及复方蛋氨酸胆碱片(1.2g.kg-1.d-1)进行防治。实验6周后,观察大鼠肝脏病理变化并检测各组血清丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶(AST)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和肝组织TC、TG、丙二醛(MDA)、超氧化物歧化酶(SOD)的水平。结果与模型组相比,HXC高剂量可以明显降低肝湿质量与肝指数,显著降低血清中的ALT、AST、TC、TG、LDL-C及肝组织中的TC、TG、MDA,升高血清中的HDL-C及肝组织中的SOD,脂肪变性和水样变性程度明显减轻。结论 HXC对高糖高脂饮食诱发的大鼠NAFLD具有明显的改善作用,其机制可能与调节血脂、减少脂质在肝脏中堆积以及提高机体抗氧化活力,抑制脂质过氧化反应有关。     

红麻茶的降脂保肝作用研究

目的 观察红麻茶对大鼠高糖高脂饲料所致非酒精性脂肪肝(NAFLD)的降脂保肝作用.方法 将40只SD大鼠随机分为5组:对照组、模型组、红麻茶低剂量组、红麻茶高剂量组、复方蛋氨酸胆碱片组,除对照组喂基础饲料外,其余各组喂高糖高脂饲料;给药组给予不同剂量的红麻茶(2.42、7.26 g·kg-1·d-1)以及复方蛋氨酸胆碱片(1.2g·kg-1·d-1)进行灌胃给药,连续6周,观察大鼠肝脏病理变化并检测各组血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶(AST)和肝组织TC、TG、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)及丙二醛(MDA)的水平.结果 红麻茶高剂量能明显降低肝指数、血清ALT、AST,降低血清与肝TC、TG、LDL-C及肝组织中的MDA,升高GSH及SOD,且肝细胞脂肪变性和水样变性程度明显减轻.结论 红麻茶具有明显的降脂保肝作用,且优于复方蛋氨酸胆碱片.能显著降低体内血脂和肝内脂肪,降低转氨酶水平,并且提高机体抗氧化活力,明显抑制脂质过氧化及清除体内自由基.     

水飞蓟油对脂肪肝干预的初步研究

目的探讨水飞蓟油对小鼠脂肪肝辅助治疗作用的初步研究。方法 50只小鼠随机分为5组,每组10只,分为正常对照组、模型组、水飞蓟油低、中、高剂量组,除正常对照组,其他组均通过喂养高脂饲料获得小鼠脂肪肝模型,水飞蓟油组分别给予1.0、2.0、4.0 g·kg~(-1)水飞蓟油,正常对照组与模型组给予生理盐水,连续3周给药后,检测小鼠血清中胆固醇(TC)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、丙二醛(MDA)水平,肝脏中甘油三酯(TG)、TC、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)水平,肝组织中氧化抗氧化指标MDA、超氧化物歧化酶(SOD)水平。结果与模型组相比,水飞蓟油组小鼠血清中TC、ALT、AST、MDA明显下降(P<0.05或P<0.01),肝脏中TG、TC、HDL-C、LDL-C明显下降(P<0.05或P<0.01),MDA明显下降(P<0.01),SOD水平明显上升(P<0.05),并且给予水飞蓟油4.0 g·kg~(-1)的小鼠各指标差异极具统计学意义(P<0.01)。结论水飞蓟油对脂肪肝的治疗具有一定的辅助作用。     

复方尼阿措提取物对高脂血症大鼠的调血脂作用

目的:探讨复方尼阿措提取物(CNAE)的调血脂作用。方法:通过灌胃脂肪乳剂制备实验性高脂血症大鼠模型。随机分为正常对照组、模型对照组、阳性对照组(1 mL.kg-1)、柳茶水提物(SAE)低、高剂量组(6.01,2.0 g.kg-1)、CNAE低、高剂量组(8.0,16.0 g.kg-1)。除正常组外,各给药组大鼠灌胃给予脂肪乳剂,基础饲料喂养,末次给药后,腹主动脉采血测定血清总胆固醇(TC)、甘油三脂(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)的含量及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性。结果:CNAE能明显降低TC、TG、LDL-C和MDA含量(P<0.01),升高HDL-C浓度,显著提高SOD及GSH-Px酶活性(P<0.01),且降血脂作用优于SAE。结论:CNAE具有明显的调血脂和抗氧化作用,提示其可用于高脂血症的防治。     

木通皂苷D对CCl4致小鼠急性肝损伤的保护作用

目的研究木通皂苷D对CCl4致小鼠急性肝损伤的保护作用。方法采用CCl4急性肝损伤模型,小鼠ig给予不同剂量的木通皂苷D(1、0.5、0.25 g·kg-1),并以水飞蓟素(0.2 g·kg-1)为阳性对照药,采用比色法检测小鼠血清的天冬氨酸转氨酶(AST)、丙氨酸氨基转移酶(ALT)及肝脏中还原性谷胱甘肽(GSH)、丙二醛(MDA)、超氧化物歧化酶(SOD)的含量。结果各剂量木通皂苷D能显著降低CCl4所致小鼠血清中AST、ALT的水平(P<0.01),同时升高肝脏组织中GSH、SOD的水平(P<0.05),降低肝脏组织中MDA的含量(P<0.05)。结论木通皂苷D对CCl4所致小鼠急性肝损伤具有显著的保护作用,其机制可能与抗氧化作用有关。     

五味子粗多糖提取物对大鼠肝纤维化的防治作用研究

目的:研究五味子粗多糖提取物对复合病因诱导的大鼠肝纤维化的防治作用。方法:实验分为6组,即正常对照(生理盐水)、模型(生理盐水)、秋水仙碱(0.1mg·kg-1)和五味子粗多糖提取物高、中、低剂量(400、200、100mg·kg-1)组。腹腔注射CCl4复制大鼠肝纤维化模型;灌胃给药。检测大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)的活性,肝匀浆丙二醛(MDA)和羟脯氨酸(HOP)的含量以及超氧化物岐化酶(SOD)的活性;形态学上观察肝组织病理学变化,用细胞图像分析系统(CIAS)对肝纤维化进行半定量。结果:与正常对照组比较,Massion染色显示模型组肝纤维化明显,有大量胶原纤维存在,肝小叶结构紊乱,血清ALT和AST显著升高,肝中MDA和HOP含量显著升高,SOD活性显著下降(P<0.01)。与模型组比较,各用药组大鼠血清ALT和AST显著降低;肝中MDA含量下降,SOD活性升高,具有显著性差异(P<0.01),并呈剂量依赖效应;肝HOP含量及胶原面积百分比显著下降(P<0.01)。结论:五味子多糖可减轻肝损害、肝脂质过氧化和肝纤维化的作用。     

长柄扁桃种仁水煎液对高脂血症大鼠血脂的影响

目的：观察长柄扁桃种仁水煎液不同剂量对高血脂模型大鼠血脂的影响。方法：采用高脂饲料喂养法建立高脂血症大鼠模型,分为长柄扁桃种仁水煎液低、中、高剂量组（0.5g·kg-1、1.0g·kg-1、1.5g·kg-1）,阳性组（血脂康胶囊0.0617g/kg）,模型组和空白对照组。灌胃给药期间继续喂食高脂饲料,7周后测定血清中总胆固醇（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）的含量。结果：与高脂模型组比较,长柄扁桃种仁高剂量组能显著降低高脂血症大鼠的TC（P<0.05）、LDL-C （P<0.01）含量;低、中剂量组无显著差异。结论：长柄扁桃种仁水煎液对高脂血症大鼠具有降血脂作用,对高脂血症的发生有一定的预防作用。     

丹红脂肝清胶囊对实验性大鼠脂肪肝的作用

目的:研究丹红脂肝清胶囊对复合因素所致的脂肪肝的治疗作用。方法:大鼠在小剂量四氯化碳致肝损伤的基础上,合并应用高脂饮食复制大鼠脂肪肝模型。于造模成功后分别给予不同浓度的药物,以血清及肝脏甘油三酯、总胆固醇的含量,血清超氧化物歧化酶和丙二醛及肝脏游离脂肪酸(freefatty acids,FFA)含量为衡量标准,观察药物的治疗效果。结果:与大鼠脂肪肝模型组相比较,丹红脂肝清胶囊高剂量组(0.4 g.kg-1)血清TC、肝脏TG有显著降低(P<0.05);丹红脂肝清胶囊低、中、高剂量组(0.1、0.2、0.4 g.kg-1)血清TG、肝脏FFA含量有显著降低(P<0.01,P<0.05);丹红脂肝清胶囊中、高剂量组(0.20、.4 g.kg-1)肝脏TC、血清MDA有显著降低(P<0.01,P<0.05);丹红脂肝清胶囊低、中、高剂量组(0.1、0.2、0.4 g.kg-1)血清SOD有显著升高(P<0.01,P<0.05)。丹红脂肝清胶囊胶囊高、中、低剂量组病理形态学改变较模型组均有明显改善。结论:丹红脂肝清胶囊对复合因素引起的脂肪肝有很好的治疗作用。     

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。     

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.