地顶胞霉菌丝体对酒精诱导小鼠急性肝损伤的保护作用

目的研究地顶胞霉菌丝体(AMM)对酒精所致小鼠急性肝损伤的保护作用。方法采用酒精灌胃造成小鼠急性酒精性肝损伤模型,测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)的活性和肝脏匀浆中超氧化物歧化酶(SOD)的活性及丙二醛(MDA)的含量,HE染色观察AMM对酒精小鼠肝脏形态学影响。结果 AMM(1 000 mg.kg-1、500 mg.kg-1)可降低血清中ALT、AST活性及肝组织中MDA的含量;升高肝组织匀浆中SOD的活性;HE染色结果显示AMM能明显减轻肝脏的病理损伤。结论 AMM对酒精所致小鼠急性肝损伤模型具有一定的保护作用。     

丝毛飞廉总黄酮对小鼠肝损伤中氧化应激介质生成的影响

目的 研究丝毛飞廉总黄酮(FGC)对绵羊红细胞(SRBC)诱发迟发型变态反应致小鼠肝损伤中氧化应激介质生成的影响.方法 预给予小鼠不同剂量的FGC(14、28、56 g·kg-1),连续ig7 d,第7日ip SRBC(红细胞个数为1.0×109 ·mL-1,剂量为10 mL·kg-1)致敏,12 d后用SRBC再次致敏,22 d后用SRBC肝穿刺攻击,诱发免疫性肝损伤,24 h后测定小鼠脏器指数,紫外分光光度法测定血清转氨酶(ALT、AST)水平,氧化应激介质丙二醛(MDA)的含量及小鼠肝微粒体中超氧化物歧化酶(SOD)活性,单细胞凝胶电泳法检测肝细胞中DNA氧化损伤水平.结果 模型组脏器指数及血清ALT、AST与空白组比较均有显著性差异(P＜0.05),表明SRBC诱发迟发型变态反应致小鼠肝损伤实验模型建立成功;FGC预给药组与造模组比较,小鼠脏器指数、血清中AST、ALT水平、SOD活性、MDA含量及彗星扫尾细胞的百分率均有显著性差异(P＜0.05).结论 预先给予FGC(14、28、56 g·kg-1)可使SRBC诱发迟发型变态反应致小鼠肝损伤肝损伤中氧化应激反应减轻,并可显著降低肝细胞核DNA单链断裂氧化损伤水平,对免疫性肝损伤有保护作用.     

脑肠肽通过抗炎抗氧化作用发挥酒精性肝损伤的保护作用

目的研究脑肠肽对小鼠酒精性肝损伤的保护作用。方法采用4周5%酒精饲料喂饲加5 g·kg-1的高剂量酒精灌胃诱导酒精性肝损伤模型,用分光光度法检测血清中ALT、AST和肝匀浆MDA、SOD、GSH-Px含量;Real-time PCR法检测肝脏中炎症细胞因子TNF-α、IL-1β、IFN-γ、IL-6和MCP-1的表达。HE染色检测肝脏病理改变。结果这种慢性酒精喂饲+单剂量大剂量酒精灌胃模式可明显诱导酒精性肝损伤,可导致明显的转氨酶升高、脂肪肝和炎症浸润。给予脑肠肽(5、10、20μg·kg-1)ip后可明显降低酒精性肝损伤小鼠增高的血清ALT、AST活性,改善酒精肝病理改变和炎症浸润;并能减少肝匀浆MDA含量,使降低的肝匀浆SOD活性升高;降低酒精性肝损伤小鼠肝脏的炎症细胞因子TNF-α、IL-1β、IFN-γ、IL-6和MCP-1的mRNA表达。结论脑肠肽对小鼠酒精性肝损伤具保护作用,其机制与抗氧化和抑制炎症作用有关。     

荞麦花叶芦丁对小鼠酒精性肝损伤的保护作用

目的探讨荞麦花叶芦丁(RBFL)对小鼠酒精性肝损伤的保护作用。方法 72只小鼠随机均分为6组:正常组(A)、模型对照组(B)、三个剂量RBFL组(R1组:75 mg.kg-1.d-1;R2组:150 mg.kg-1.d-1;R3组:300 mg.kg-1.d-1)和RBFL标准品对照组(D组:150 mg.kg-1.d-1)。用50%乙醇按10 ml.kg-1.d-1连续灌胃10 d,制备小鼠酒精性肝损伤模型。测定血清AST、ALT活力,计算肝重指数(LI),测定肝组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,镜下观察肝组织病理改变来判断RBFL对酒精性肝损伤小鼠的保护作用。结果 RBFL不同程度地降低了酒精性肝损伤小鼠的死亡率和体重下降率,抑制肝损伤小鼠的LI、AST和MDA,显著增强肝损伤小鼠肝组织SOD活性;病理组织学显示,RBFL能显著改善酒精损伤肝细胞的形态学变化。结论 RBFL对小鼠酒精性肝损伤有显著的保护作用,其机制可能与抑制脂质过氧化损伤有关。     

番茄红素对雷公藤多苷致小鼠肝损害的保护作用

目的：建立雷公藤多苷肝损伤模型,研究番茄红素对雷公藤多苷致小鼠肝损伤的保护作用。方法：昆明种小鼠40只,随机分为空白组、模型组、番茄红素高剂量组（20mg/kg）、番茄红素低剂量组（10mg/kg）,各组预防性给药（或色拉油）6d后除空白组以外,用20倍常规剂量（270mg/kg）雷公藤多苷建立小鼠肝损伤模型,观察番茄红素对小鼠血清转氨酶（ALT、AST）、肝组织氧化指标及肝脏病理学的影响。结果：雷公藤多苷可使小鼠血清ALT、AST,肝体指数明显增高（P〈0.05）;与模型组比较,番茄红素各剂量组血清AST、ALT含量明显降低（P〈0.05）,小鼠肝组织SOD活性明显升高,降低MDA含量（P〈0.01）;肝组织的病理改变明显减轻（P〈0.05）。结论：番茄红素对雷公藤多苷致肝损伤具有良好的保护作用。     

柴芦疏肝解毒胶囊对动物实验性肝损伤的保护作用

目的研究柴芦疏肝解毒胶囊对动物实验性肝损伤的保护作用。方法采用白酒制备小鼠酒精实验性肝损伤模型,柴芦疏肝解毒胶囊按高、中、低剂量灌胃,连续8周,测定血清天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)的含量,检测肝组织丙二醛(MDA)及还原型谷胱甘肽(GSH)的含量,并观察肝组织的病理组织学改变。结果柴芦疏肝解毒胶囊高、中剂量组可显著降低小鼠血清AST、ALT含量,与肝损模型组比较,差异显著(P<0.01或P<0.05);受试样品高、中剂量组小鼠肝组织的MDA含量均值均低于肝损模型组;GSH含量均高于肝损模型组;肝组织病理学改变较肝损模型组显著减轻。结论柴芦疏肝解毒胶囊对小鼠酒精实验性肝损伤具有保护作用,该作用随剂量的增大而增强。     

灯盏乙素对异烟肼和利福平合用致小鼠肝损伤的保护作用

目的:观察灯盏乙素对异烟肼(INH)和利福平(RFP)合用致小鼠肝损伤的保护作用.方法:小鼠每天同时灌胃RFP和INH各100 mg·kg-1,2 h后灌胃灯盏乙素50,100,200 mg·kg-1,qd,连续给药10 d,末次给药16 h后,取血和各器官组织,测定肝、脾和胸腺指数、血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)的活性、肝匀浆中超氧化物歧化酶(SOD)、脂质过氧化物丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)以及一氧化氮(NO)的含量.结果:灯盏乙素能显著降低RFP和INH合用致肝损伤小鼠的肝指数、血清ALT和AST活性、肝匀浆中的MDA和NO含量,并能显著提高肝匀浆中的SOD和GSH-Px活性.结论:灯盏乙素对RFP和INH合用致小鼠肝损伤具有明显的保护作用,可能与其抗脂质过氧化及调节体内NO水平有关.     

β-酪啡肽-7对小鼠酒精性肝损伤防治作用的研究

目的研究β-酪啡肽-7(β-CM-7)对小鼠酒精性肝损伤的防治作用。方法 60只昆明♂小鼠随机分为6组(每组10只):对照组、模型组、护肝片组(0.3 g.kg-1)、β-CM-7高剂量组(灌胃剂量:2.0×10-1g.L-1)、β-CM-7中剂量组(灌胃剂量:2.0×10-2g.L-1)和β-CM-7低剂量组(灌胃剂量:2.0×10-3g.L-1),除对照组外均采用梯度酒精灌胃的方法建立酒精性肝损伤动物模型,同时除模型组外各组分别给予药物治疗12周。观察用药前后各组小鼠生化指标血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、甘油三酯(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)和肝组织匀浆中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)水平的变化。结果β-CM-7高剂量组能够明显降低酒精性肝损伤小鼠血清中ALT、AST、TG、LDL-C水平(P<0.05或P<0.01),提高血清HDL-C的含量,减少肝组织匀浆的MDA含量(P<0.05或P<0.01),升高肝匀浆SOD,GSH-Px的水平(P<0.05或P<0.01)。结论β-酪啡肽-7对小鼠酒精性肝损伤有防治作用,可能与其调节脂质代谢,抗脂质过氧化     

柚皮素对四氯化碳致小鼠化学性肝损伤中氧化应激介质生成影响的实验研究

目的 考察柚皮素(黄酮类化合物)对小鼠化学性肝损伤中氧化应激介质生成的影响.方法 用灌胃法,小鼠连续7天预给予柚皮素(25,50,100 mg·kg-1),第7日经腹腔单次注射四氯化碳(CCl4,1 mL·kg-1)诱发化学性肝损伤.24 h后用紫外分光光度法测定血清转氨酶(ALT、AST)水平,氧化应激介质丙二醛(MDA)含量,及肝微粒体超氧化物歧化酶(SOD)活性;用单细胞凝胶电泳法检测肝细胞中DNA氧化损伤水平.结果 与对照组相比,CCl4化学损伤组小鼠的血清ALT水平显著升高,氧化应激介质生成增多,肝细胞DNA氧化损伤断裂显著增多.柚皮素预处理组,CC4l急性肝损伤中血清转氨酶水平虽然未见明显变化,但柚皮素在其高剂量组(100 mg·kg-1)可使MDA水平有下降趋势,SOD活性有升高趋势且可显著性地降低CCl4损伤所致彗星拖尾细胞的百分率.结论 预先给予柚皮素(25,50,100mg·kg-1)可使CCl4所致急性肝损伤中氧化应激反应减轻,并可显著降低肝细胞核DNA单链断裂氧化损伤水平.     

秃疮花提取物对小鼠免疫性肝损伤的保护作用

目的　探讨秃疮花提取物 (DLF)对卡介苗 (BCG)和脂多糖 (LPS)诱导的小鼠免疫性肝损伤的影响。方法　ivBCG和LPS诱导小鼠免疫性肝损伤 ,在注射LPS前 ,小鼠ip不同剂量的DLF(0 5、1 0、2 0g·kg-1) ,连续 10d。观察血清谷丙转氨酶 (ALT)、谷草转氨酶 (AST)、乳酸脱氢酶 (LDH)的活性及血清白蛋白 (ALB)、球蛋白 (GLB)含量变化 ,测定肝组织匀浆中脂质过氧化产物丙二醛 (MDA)含量和超氧化物歧化酶(SOD)活性 ,同时进行肝组织病理学观察。结果　不同剂量的DLF治疗组小鼠血清ALT、AST、LDH活性及肝组织匀浆MDA含量均低于模型组 ,血清蛋白维持正常比例 ,且肝组织损伤不同程度地减轻。结论　秃疮花提取物对BCG和LPS诱导的小鼠免疫性肝损伤具有一定的保护作用     

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.     

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.