水飞蓟宾对小鼠腹腔巨噬细胞释放纤维化因子的影响

目的:研究水飞蓟宾对小鼠腹腔巨噬细胞释放纤维化因子的影响。方法:小鼠腹腔巨噬细胞先后用卡西霉素和脂多糖刺激培养24h诱导纤维化因子。巨噬细胞培养上清中促胶原合成活性和转化生长因子β活性分别采用³H-脯氨酸掺入法和雕肺上皮Mv-1-Lu细胞测定。结果:水飞蓟宾(6.25-50μg／mL)以浓度依赖方式抑制巨噬细胞产生胶原刺激活性和转化生长因子β₁。结论:水飞蓟宾减少巨噬细胞释放促纤维化因子可能是其保肝抗硬化机制之一。     

4种黄酮化合物对小鼠腹腔巨噬细胞纤维化因子产生及作用的影响

目的：研究黄颜木素、槲皮素、芹菜素和根皮素对小鼠腹腔巨噬细胞纤维化因子的产生及作用的影响。方法：小鼠腹腔巨噬细胞先后用卡西霉素和脂多糖刺激培养24h诱导纤维化因子。巨噬细胞上清促肝星状细胞增殖和胶原合成分别采用结晶紫染色法和^3H-脯氨酸掺入法测定。转化生长因子β活性采用雕肺上皮Mv-1-Lu细胞测定。结果：黄颜木素、槲皮素、芹菜素和根皮素（12．5～50μmol／L）以浓度依赖方式抑制巨噬细胞产生胶原刺激活性和转化生长因子β1，但对巨噬细胞产生促细胞增殖作用无影响。结论：黄颜木素、槲皮素、芹菜素和根皮素具有减少促纤维化因子产生的作用。     

苦参碱抑制小鼠腹膜巨噬细胞纤维化细胞因子的产生和作用

目的：研究苦参碱对小鼠腹腔巨噬细胞释放纤维化细胞因子以及对巨噬细胞条件培养基（MCM）促HSC-T6大鼠储脂细胞和NIH3T3成纤维细胞增殖和胶原合成的影响。方法：巨噬细胞先后用卡西霉素1μmol/L和脂多糖100μg/L刺激诱导产生纤维化因子,细胞上清中促细胞增殖活性和促胶原合成活性分别用结晶紫染色法和[^3H]-脯氨酸掺入法测定,转化生长因子β活性采用貂肺上皮Mv-l-Lu细胞增殖抑制法测定。结果：苦参碱（0.5-2mmol/L）显著抑制LPS诱导的促胶原合成活性和TGFβ的产生,但不能抑制巨噬细胞产生促细胞增殖活性;苦参碱还能剂量依赖地抑制MCM诱导的HSC-T6细胞以及NIH3T3细胞增殖和胶原合成。结论：苦参碱抗肝纤维化作用与抑制巨噬细胞纤维化因子的产生和阻断其作用有关。     

肝星状细胞HSC-T6体外肝纤维化模型的建立

目的:研究以肝星状细胞HSC-T6为靶细胞,建立体外肝纤维化模型.方法:小鼠腹腔巨噬细胞先后用卡西霉素和脂多糖刺激培养24h制备巨噬细胞条件培养基.肝星状细胞增殖和胶原合成分别采用结晶紫染色法和3H-脯氨酸掺入法测定.结果:血清和巨噬细胞条件培养基可显著促进HSC-T6细胞增殖与胶原合成.IL-1、TNF、EGF、FGF和PDGF均可促进HSC-T6细胞增殖,其中PDGF的促增殖能力最强.TGFβ1可剂量依赖地促进HSC-T6细胞胶原的合成.结论:用血清、巨噬细胞条件培养基、PDGF或TGFβ刺激HSC-T6细胞增殖和胶原合成作为体外肝纤维化模型是可行的.     

6种黄酮化合物对大鼠肝星状细胞胶原合成的抑制作用

目的：研究黄颜木素、槲皮素、芹菜素、根皮素、橙皮素和查尔酮对血清、巨噬细胞培养上清液和转化生长因子β1刺激的大鼠肝星状细胞HSC—T6胶原合成的影响。方法：^3H-脯氨酸掺入法测定细胞胶原合成。结果：黄颜木素、槲皮素、芹菜素、根皮素、橙皮素和查尔酮（12．5～50μmol／L）以浓度依赖方式抑制血清、巨噬细胞上清和转化生长因子β1诱导的胶原合成。结论：黄颜木素、槲皮素、芹菜素、根皮素、橙皮素和查尔酮具有抑制肝星状细胞胶原合成的作用，可能具有潜在的肝纤维化治疗作用。     

rmuGM-CSF增强巨噬细胞抗白念珠菌活性研究

目的： 研究重组小鼠粒细胞巨噬细胞集落刺激因子(rmuGM CSF)对巨噬细胞抗白念珠菌活性的调节作用。方法：分别将浓度为100，200，300，400 U·mL 1的rmuGM CSF与小鼠腹腔巨噬细胞共同培养2～5 d，然后测定巨噬细胞的抗白念珠菌活性。结果： rmuGM CSF可增强巨噬细胞的抗白念珠菌活性，作用呈剂量依赖性，且随着与巨噬细胞共培养时间的延长，增强效应不降低。结论： rmuGM CSF能增强巨噬细胞的抗白念珠菌活性，增强效应强而持久。     

商陆多糖I对小鼠脾淋巴细胞增殖及脾淋巴细胞、巨噬细胞分泌细胞因子的影响

商陆多糖Ⅰ(Phytolacca acinosa polysaccharides Ⅰ,PAP-Ⅰ)体外能显著促进小鼠脾淋巴细胞增殖,促进丝裂原诱导的淋巴细胞转化及双向混合淋巴细胞反应。检测PAP-Ⅰ和小鼠脾淋巴细胞培养上清液发现PAP-Ⅰ可显著促进小鼠脾淋巴细胞产生白细胞介素2(IL-2)及集落刺激因子(colony stimulating factor,CSF)。PAP-Ⅰ和小鼠腹腔巨噬细胞培养上清液中也存在CSF活性及促进重组粒单系集落刺激因子诱导骨髓细胞增殖的细胞因子。PAP-Ⅰ,ip可显著促进小鼠脾淋巴细胞增殖及IL-2产生。     

商陆多糖I对小鼠脾淋巴细胞增殖及脾淋巴细胞、巨噬细胞分泌细胞因子的影响

商陆多糖Ⅰ(Phytolacca acinosa polysaccharides Ⅰ,PAP-Ⅰ)体外能显著促进小鼠脾淋巴细胞增殖,促进丝裂原诱导的淋巴细胞转化及双向混合淋巴细胞反应。检测PAP-Ⅰ和小鼠脾淋巴细胞培养上清液发现PAP-Ⅰ可显著促进小鼠脾淋巴细胞产生白细胞介素2(IL-2)及集落刺激因子(colony stimulating factor,CSF)。PAP-Ⅰ和小鼠腹腔巨噬细胞培养上清液中也存在CSF活性及促进重组粒单系集落刺激因子诱导骨髓细胞增殖的细胞因子。PAP-Ⅰ,ip可显著促进小鼠脾淋巴细胞增殖及IL-2产生。     

TGF—β1对人牙周膜成纤维细胞合成胶原的影响

目的：观察不同浓度的转化生长因子β1对体外培养的人牙周膜成纤维细胞合成胶原的影响。方法：采用组织块培养技术进行人牙周膜成纤维细胞的体外培养,采用羟脯氨酸试剂盒来观察细胞合成胶原的情况。结果：0．1、1．0、10．0、50．0ng／ml的转化生成因子β1可以促进牙周膜成纤维细胞合成胶原,其中10ng／ml的TGF—β1在48h促胶原合成作用最明显,差异有统计学意义（P〈0．05）。结论：转化生长因子β1有促进人牙周膜成纤维细胞合成胶原的作用。     

水飞蓟宾的抗肿瘤、抗氧化和免疫调节分子药理学机制研究进展

 水飞蓟宾 (silibinin) 来源于菊科植物水飞蓟 (Silybum marianum), 为黄酮木脂素类化合物, 具有明显抗氧化和抗炎的特性, 临床上作为保肝药物长期应用于中国、德国和日本等国家。近年来发现水飞蓟宾有明显的抗肿瘤活性, 其主要机制为抑制肿瘤受体型酪氨酸激酶 (receptor tyrosine kinase, RTK) 的活性, 如抑制表皮生长因子受体1 (epidermal growth factor receptor 1, EGFR) 和胰岛素样生长因子1受体 (insulin-like growth factor 1 receptor, IGF-1R) 及其下游信号分子的活化。同时因为发现水飞蓟宾对羟自由基 (•OH) 的选择性清除, 以及对核因子κB (nuclear factor-κB, NF-κB) 的特异性抑制, 使其抗氧化和抗炎的分子机制更为明确。一些新的发现如水飞蓟宾通过抑制氧化应激和炎症反应而改善β-淀粉样蛋白 (amyloid β protein, Aβ) 引起的认知功能障碍等对拓展水飞蓟宾的药用前景具有重要价值。本文对水飞蓟宾的分子药理机制进行总结, 主要从水飞蓟宾抑制肿瘤RTK信号转导、抗氧化与自由基清除、调节免疫与炎症3个方面进行了阐述。     

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.