丹皮总甙对小鼠免疫性肝损伤的保护作用

目的研究丹皮总甙（TGM）对小鼠免疫性肝损伤的保护作用。方法：小鼠分别尾ivBCG和LPS后，检测其血清ALT和AST活性、TPr含量及其脏器重量指数，并用硫代巴比妥酸法测其血清与肝组织中LPO含量。结果：TGM50、100mg·kg(－1)·d(－1)（ig），连用9d，可显著抑制小鼠血清ALT和AST活性，降低其血清与肝组织中LPO含量，并减轻其增大的脾脏重量指数。结论：TGM预防性给药对BCG＋LPS诱导的小鼠免疫性肝损伤具有一定的保护作用。     

双孢菇胞内和胞外多糖对伴刀豆凝集素A诱导免疫性肝损伤小鼠的保护作用

目的研究双孢菇胞内多糖(IPS)和胞外多糖(EPS)对伴刀豆凝集素A(Con A)所致小鼠免疫性肝损伤的保护作用。方法小鼠预先ig给予IPS或EPS 100,200和400 mg·kg~(-1),每日1次,连续12 d,末次给药后4 h尾静脉注射Con A 25 mg·kg~(-1)制备免疫性肝损伤小鼠模型。8 h后眼球取血,取肝、脾和胸腺。全自动生化分析仪测定血清谷丙转氨酶(GPT)和谷草转氨酶(GOT)水平。流式细胞仪检测脾细胞中CD4~+和CD8~+T淋巴细胞百分比。生化试剂盒检测血清干扰素γ(IFN-γ)和肿瘤坏死因子α(TNF-α)含量及肝组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)水平。光学显微镜观察肝组织切片的病理改变。结果与正常对照组相比,模型小鼠胸腺指数明显降低(P<0.01),肝、脾指数明显增高(P<0.01);与模型组比较,预先给予IPS 100,200和400 mg·kg~(-1)及EPS 200和400 mg·kg~(-1)小鼠胸腺指数明显升高(P<0.01),肝、脾指数均明显降低(P<0.01)。与正常对照组相比,模型小鼠血清GOT和GPT活性及TNF-α和IFN-γ含量显著升高(P<0.01);预先给予IPS及EPS 200和400 mg·kg~(-1)小鼠血清GOT和GPT活性及TNF-α和IFN-γ含量较模型组显著降低(P<0.01)。与正常对照组相比,模型小鼠肝组织SOD活性降低(P<0.01),MDA水平升高(P<0.01);与模型组比较,预先给予IPS及EPS 200和400 mg·kg~(-1)SOD活性明显升高(P<0.01),MDA水平降低(P<0.01)。与正常对照组相比,模型小鼠脾细胞中CD4~+T淋巴细胞百分比和CD4~+/CD8~+T淋巴细胞比值明显下降(P<0.01);预先给予IPS和EPS 400 mg·kg~(-1)CD4~+T淋巴细胞百分比与模型组比较明显升高(P<0.01),CD4~+/CD8~+T淋巴细胞比值变化不明显。镜下观察模型组小鼠肝组织出现明显的病理改变,预先给予IPS和EPS能减轻Con A引起的病理变化。结论双孢菇IPS和EPS对小鼠免疫性肝损伤有一定的保护作用,其机制可能与清除自由基、抑制脂质过氧化和调节免疫系统平衡有关。     

山芝麻水提取物对小鼠免疫性肝损伤的保护作用

目的观察山芝麻水提取物对小鼠免疫性肝损伤的保护作用。方法将60只小鼠随机分为正常对照组、模型组、日达仙阳性对照组(4.2μg.kg-1.d-1),以及山芝麻高、中、低剂量组(20,10,5 g.kg-1.d-1),各组预防性给药15 d,除正常对照组外,其余各组小鼠尾静脉注射20 mg.kg1刀豆蛋白A(Con A)。12 h后测定血清谷草转氨酶(AST)、谷丙转氨酶(ALT)的活性,流式细胞术测定全血中CD3+、CD4+、CD8+T细胞亚群比率,ELISA方法测定血清肿瘤坏死因子(TNF-α)和γ干扰素(IFN-γ)的水平。结果与模型组比较,10,20μg.kg-1.d-1剂量的山芝麻能明显降低Con A介导的肝损伤小鼠血清中AST、ALT的水平,显著提高CD3+、CD4+、CD4+/CD8+比率,明显降低血清中炎性细胞因子IFN-γ和TNF-α的含量。结论山芝麻水提取物对免疫性肝损伤具有保护作用,其机制可能与调整T细胞亚群的活性和减少炎性细胞因子的作用有关。     

鲨肝活性肽S-8300对小鼠急性肝损伤的保护作用

目的：研究鲨肝活性肽S-8300对四氯化碳(CCl4)小鼠肝损伤的保护作用。方法：采用CCl4致小鼠肝损伤，观察肝组织切片；测定生化指标，检测小鼠腹腔注射S-8300后血清谷丙转氨酶(sGPT)、血清谷草转氨酶(sGOT)和乳酸脱氢酶(LDH)活性，肝脏超氧化物歧化酶(SOD)活性与丙二醛(MDA)和谷胱甘肽(GSH)含量。结果：S-8300能明显减轻CCl4所致小鼠急性肝损伤；降低血清GPT、GOT、LDH活性及降低肝组织MDA含量，增加肝组织GSH含量和提高SOD活性。结论：鲨肝活性肽S-8300对急性肝损伤有明显的保护作用。     

荔枝核对小鼠肝炎动物模型的实验研究

目的探讨荔枝核对小鼠免疫性肝炎及急性肝损伤保护作用研究。方法小鼠iv卡介苗(BCG)5×106个菌/鼠;11天后再iv脂多糖(LPS)7.5μg/只,造成免疫性肝炎模型,对小鼠四氯化碳(CCL4)和硫代硫酰胺(TAA)所引起急性中毒模型。结果荔枝核能明显降低免疫性肝炎及急性肝损伤模型小鼠血清谷丙氨酸转氨酶(ALT),谷草转氨酶(AST)的作用(P<0.01);血清的超氨化物岐化酶(SOD)的活性升高,血清(MDA)含量明显降低。结论荔枝核对小鼠免疫性肝炎及急性肝损伤保护有保护作用。     

胸腺肽对小鼠免疫性肝损伤保护研究

目的 研究胸腺肽对小鼠免疫性肝损伤的保护作用.方法 采用卡介苗联合脂多糖诱导法,建立免疫性肝损伤的小鼠模型,观察胸腺肽对小鼠免疫性肝损伤的保护作用.结果 胸腺肽能明显降低免疫性肝炎模型小鼠血清丙氨酸氨基转移酶(ALT)的活性,并能显著减轻肝炎小鼠的肝指数和脾指数(P＜0.05).结论 胸腺肽对小鼠免疫性肝损伤有保护作用.     

罗汉果甜苷对小鼠实验性肝损伤保护作用的研究

目的:研究罗汉果甜苷(Mog)对实验性肝损伤小鼠的保护作用。方法:以四氯化碳诱导小鼠急性肝损伤;以卡介苗(BCG)加脂多糖(LPS)诱导小鼠免疫性肝损伤。检测血清中谷丙胺酸氨基转移酶(ALT)、谷草胺酸氨基转移酶(AST)的活性;检测肝组织中超氧化物歧化酶(SOD)的活性和丙二醛(MDA)的含量;并进行病理学检查。结果:Mog小鼠对急性、免疫性肝损伤,有降低血清中ALT、AST活性的作用;对免疫性肝损伤的肝组织匀浆有升高SOD活性、降低MDA含量的作用;并能显著减轻肝组织病理变化程度。结论:Mog对小鼠急性肝损伤、免疫性肝损伤有保护作用,其机制可能与Mog的抗脂质过氧化作用有关。     

白芍总苷对卡介苗加脂多糖引起的小鼠免疫性肝损伤的保护作用

目的　研究白芍总苷对小鼠免疫性肝损伤的保护作用。方法　在建立BCG +LPS诱导免疫性肝损伤小鼠模型的基础上 ,分光光度法检测血清中ALT、AST、NO水平和肝匀浆MDA、GSH Px、SOD含量 ;放免法检测TNF α的生物学活性 ;细胞增殖法测定脾淋巴增殖反应。结果　白芍总苷 (6 0、12 0、2 4 0mg·kg-1)ig给药可明显降低免疫性肝损伤小鼠增高的血清ALT、AST活性 ,同时能减少肝匀浆MDA含量 ,使降低的肝匀浆GSH Px、SOD活性升高 ,进一步研究发现白芍总苷可明显抑制免疫性肝损伤小鼠血清NO和TNF α的产生。白芍总苷还可抑制小鼠腹腔巨噬细胞TNF α的产生 ,对ConA诱导的脾淋巴增殖反应具有恢复作用 ,而对LPS诱导的脾淋巴增殖反应无明显影响。结论　白芍总苷对免疫性肝损伤具有保护作用。     

丹参多糖对小鼠免疫性肝损伤的保护作用

目的探讨丹参多糖对卡介苗（BCG）和脂多糖（LPS）诱导的小鼠免疫性肝损伤的保护作用。方法尾静脉注射BCG和LPS诱导小鼠免疫性肝损伤,对比小鼠脏器系数,检测血清谷草转氨酶（AST）、谷丙转氨酶（ALT）、一氧化氮（NO）的水平以及比较肝组织匀浆中肿瘤坏死因子α（TNF-α）、白介素1β（IL-1β）的含量。结果丹参多糖可显著改善免疫性肝损伤小鼠的胸腺、肝脏、脾脏系数,降低血清中ALT、AST、NO的活性以及肝组织匀浆中TNF-α、IL-1β的含量。结论丹参多糖对免疫性肝损伤具有显著的保护作用。     

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.     

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.