脂联素对2型糖尿病心肌病变的保护作用

脂联素（adiponectin, ANP）具有胰岛素增敏、抗动脉粥样硬化、抗炎症等作用,它可以通过多种机制对糖尿病心肌病变起到保护作用。本文概述了脂联素通过抑制心肌纤维化改善糖尿病性心肌病（diabetic cardiomyopathy, DCM）这一领域的研究进展。     

脂连素在胰岛素抵抗综合征防治中的作用

脂连素由脂肪细胞分泌,在调节糖脂代谢过程中发挥着重要作用,具有改善胰岛素抵抗、抗炎、抗动脉粥样硬化等多种功能.胰岛素抵抗状态下血浆脂连素水平明显降低,补充脂连素可改善胰岛素抵抗,脂连素将成为胰岛素抵抗综合征极有潜力的防治靶点.本文重点综述脂连素在胰岛素抵抗综合征防治靶点的研究进展.     

脂氧素在炎症中作用的研究进展

脂氧素（lipoxin,LX）是来源于花生四烯酸、经脂氧合酶催化合成的一类生物活性物质。在哺乳动物中,其主要包括脂氧素A4（LXA4）和脂氧素B4（LXB4）。研究表明,在炎症过程中,LX能够抑制白细胞向炎症部位的趋化并促进巨噬细胞吞噬局部凋亡的粒细胞及其他损伤细胞,从而抑制炎症的进程,促进炎症的消退。由于其在炎性疾病中所发挥的独特的抗炎和促进炎症消退的功能而被关注。本文主要介绍近年来LX在合成、代谢、生物学功能及疾病发生中作用的研究进展。     

脂联素对心血管保护作用的研究进展

脂联素由脂肪组织分泌参与调节多种代谢过程的脂肪细胞因子。临床和基础科学研究确定了脂联素的心血管保护作用,其主要有抗动脉粥样硬化、促血管再生及心肌细胞保护等。故将详细描述脂联素在心血管疾病保护中的重要作用,及目前其分子机制的研究热点、方向和成果,并展望脂联素未来研究方向和潜在的临床应用前景。     

脂联素的血管内皮保护作用及相关的基因治疗研究

脂联素-脂肪细胞特异性分泌的蛋白,有着血管内皮保护作用。由于它的胰岛素样血管活性作用、抗炎、抗氧化、抗动脉粥样硬化等作用而被认为是调节脂肪血管轴的重要因子。本综述着重论述脂联素对血管内皮细胞的保护功能及其血管保护相关的基因治疗研究。     

连轺化学成分研究

从连轺中分离得到３个化合物。经化学和波谱方法鉴定，它们分别是熊果酸（ｕｒｓｏｌｉｃａｃｉｄ，Ⅰ），连翘甙（ｐｈｉｌｌｙｒｉｎ，Ⅱ）和连翘脂素（ｐｈｉｌｌｙｇｅｎｉｎ，Ⅲ），均为首次从连轺中分离而得。     

非酒精性脂肪性肝病患者肝组织脂联素表达及其意义

目的探讨肝组织脂联素表达在非酒精性脂肪性肝病（NAFLD）发病机制中的作用及地位,为NAFLD的预防及治疗提供新的思路。方法47例NAFLD患者及20例正常对照均测量身高、体重,计算体重指数（BMI）;分别应用ELISA方法测定血清脂联素（adiponectin）浓度、血清肿瘤坏死因子-α（TNF-α）浓度;采用稳态模式评估法,计算胰岛素抵抗指数（HOMA-IR）;对肝组织进行HE、Masson染色及脂联素免疫组化染色,对脂联素表达量进行半定量分析。结果非酒精性脂肪性肝炎（NASH）组肝组织脂联素表达较对照组及单纯性脂肪肝组显著减少（P〈0.05）,与血清脂联素浓度呈显著正相关（P〈0.01）,与血清TNF-α浓度、ALT、HOMA-IR及肝组织炎症、纤维化程度呈负相关（P〈0.01）,而与脂变程度不相关（P〉0.05）。多元线性逐步回归分析显示,肝组织脂联素表达是肝组织炎症及纤维化发生的保护因素。结论肝组织脂联素表达在NAFLD患者肝组织炎症及纤维化发生发展中起保护性作用。     

脂联素原核表达载体PQE30/ADPN的构建及其表达与纯化

目的构建大鼠全长脂联素(fAd)和球状域脂联素(gAd)重组表达载体PQE30/ADPN,并在大肠杆菌宿主系统中表达出脂联素蛋白,对表达产物进行纯化和鉴定。方法将纯化的脂联素克隆产物与原核表达载体PQE30通过双酶切方法位点特异地连接在一起,再转化入大肠杆菌M15感受态细胞中,并用IPTG诱导表达,并通过亲和层析、去盐、去除内毒素等纯化蛋白。结果PCR获得长度分别为684bp(fAd)和402bp(gAd)的目的片段,经PQE30原核表达载体连接、筛选及序列分析后,证实所插入目的片段与GenBank中脂联素序列(序列号:NM_144744)完全一致;含重组脂联素质粒的大肠杆菌在30℃经0.5mmol.L-1IPTG诱导6h时,可溶性蛋白表达量最高。结论成功克隆大鼠脂联素基因,并在大肠杆菌中获得有效表达。     

脂氧素A_4在大鼠急性肝衰竭中的作用

目的观察脂氧素A4(LXA4)对大鼠急性肝衰竭的保护作用。方法使用D-氨基半乳糖(D-GalN)+脂多糖(LPS)建立大鼠急性肝衰竭动物模型。实验分为6组:正常组、模型组、LXA4小、中、大剂量组、四氢化吡咯二硫代氨基甲酸酯(PDTC)组。检测肝脏炎症变化、炎性细胞因子水平、凋亡指标等表达。结果大鼠急性肝衰竭时,肝脏转氨酶明显升高,肝组织炎症坏死明显,组织学评分明显升高,血清IL-6及TNF-α及肝组织TNF-αmRNA及IL-6mRNA水平明显升高;脂氧素组及PDTC组肝脏转氨酶明显下降,组织学改变均明显好转;脂氧素大剂量组与PDTC组比较,上述大部分指标之间差异有统计学意义(P0.05)。结论 LXA4对大鼠急性肝衰竭有保护作用,可减少致炎性细胞因子的分泌。     

脂联素对氧化低密度脂蛋白损伤内皮祖细胞的影响及作用机制

目的观察脂联素对氧化低密度脂蛋白（ox-LDL）损伤人外周血内皮祖细胞（EPCs）的影响,并探讨其作用机制。方法密度梯度离心法获取外周血单个核细胞,通过流式细胞仪鉴定EPCs。培养7d后,收集贴壁细胞并随机分为正常对照组,ox-LDL组（10 mg·L~（-1））及脂联素干预组（ox-LDL 10mg·L~（-1）加脂联素,浓度分别为1.25、2.5和5mg·L~（-1））。干预24h后采用细胞活力噻唑蓝（MTT）法测定细胞活力,黏附能力测定实验测定其黏附能力,并测定各组细胞上清液中白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）含量。结果 ox-LDL与EPCs作用后,各组细胞的细胞活力、黏附能力均显著下降,IL-6、TNF-α含量均显著升高;脂联素干预24h后,明显提高了EPCs的黏附能力、细胞活力,降低了IL-6、TNF-a含量。结论脂联素对EPCs具有保护作用,其机制可能与抑制炎症反应有关。     

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.