短链脂肪酸与非酒精性脂肪性肝病的研究进展

非酒精性脂肪性肝病是指除外酒精和其他明确病因引起的以肝内脂肪过度沉积为主要特征的肝脏病变,目前已成为中国第一大慢性肝病却缺乏有效的治疗方案.短链脂肪酸是肠道菌群的代谢产物,多研究认为短链脂肪酸在改善肠道损伤及减轻肝脏的脂肪变性、炎性损伤、氧化应激等方面发挥作用,从而可能延缓非酒精性脂肪性肝病的发生发展.文章主要就短链脂...     

非酒精性脂肪性肝病不容忽视

非酒精性脂肪性肝病是一种与胰岛素抵抗及遗传等密切相关的代谢应激性肝脏损伤,其病理学改变与酒精性肝病相似,但患者无过量饮酒史。非酒精性脂肪性肝病包括：非酒精性单纯性脂肪肝、非酒精性脂肪性肝炎及其相关肝硬化和肝细胞癌。     

肠道菌群和胆汁酸在非酒精性脂肪肝病中的交互作用

非酒精性脂肪性肝病（NAFLD）作为一个全球性疾病,其发病率逐年上升。研究表明,肠道菌群在代谢、免疫等方面起着重要作用,而胆汁酸是调节血糖、血脂和能量代谢的关键信号因子。两者作为肠-肝轴中的重要角色,都与非酒精性脂肪性肝病的发生、发展密切相关。阐明肠道菌群和胆汁酸在非酒精性脂肪性肝病中的复杂关联,是治疗非酒精性脂肪性肝病的重要线索。故本文综述了肠道菌群和胆汁酸在非酒精性脂肪性肝病中的交互作用,希望能为治疗非酒精性脂肪性肝病提供参考。     

老年非酒精性脂肪性肝病与原发性高血压的关系

目的探讨老年非酒精性脂肪性肝病与原发性高血压的内在关系和相互影响及作用机制。方法 154例门诊及住院的老年人根据B超检查结果分为非酒精性脂肪性肝病组96例和正常组58例,对老年非酒精性脂肪性肝病组患者伴有原发性高血压的情况及其相关因素进行分析。结果老年非酒精性脂肪性肝病组患者原发性高血压的患病率高于正常组,差异有统计学意义(P<0.05)。老年非酒精性脂肪性肝病伴有原发性高血压患者的人体质量指数、腰臀比值、空腹血糖、胰岛素浓度、高密度脂蛋白、甘油三酯、高敏C反应蛋白、胰岛素抵抗指数与正常组比较差异具有统计学意义(P<0.05);总胆固醇、低密度脂蛋白水平两组比较差异无统计学意义(P>0.05)。经多变量分析发现,老年非酒精性脂肪性肝病和原发性高血压呈显著相关[OR 1.471,95%CI(1.195,1.821),P<0.001]。结论老年非酒精性脂肪性肝病患者中原发性高血压的患病率高于正常人,可见,老年非酒精性脂肪性肝病与原发性高血压具有一定的内在关系,两者相互影响、相互作用,机制可能与胰岛素抵抗有一定的关系。     

非酒精性脂肪性肝病与2型糖尿病的研究进展

随着人们生活水平的提高和饮食结构的改变，非酒精性脂肪性肝病和2型糖尿病的发病率均逐年上升。在美国，转氨酶升高的主要病因就是非酒精性脂肪性肝病，因此，非酒精性脂肪性肝病已被认为是最常见的慢性肝脏疾病。而且，非酒精性脂肪性肝病经常与肥胖、2型糖尿病、高血压及高脂血症合并存在，危害人民健康。[第一段]     

他汀类药物在非酒精性脂肪性肝病中的应用及其安全性

非酒精性脂肪性肝病与胰岛素抵抗和遗传易感密切相关,常表现为血脂异常、血糖异常、体重增加等。因此,该人群经常需要应用他汀类药物。但是非酒精性脂肪性肝病患者常伴随肝酶升高,使得他汀类药物应用存在困难。目前,对于非酒精性脂肪性肝病患者使用他汀类药物的有效性及安全性尚未达成共识。本文对上述内容进行综述,以期对非酒精性脂肪性肝病患者合理使用他汀类药物提供依据。     

非酒精性脂肪肝患者血清脂联素水平及其与氧化应激的相关性研究

目的:探讨非酒精性脂肪性肝病患者血清脂联素水平变化及其与肝功能、氧化应激的关系。方法:选取非酒精性脂肪性肝病89例,其中非酒精性脂肪性肝病合并代谢综合征47例,健康体检者30例作为正常对照组。行腹部B超检查,测量身高、体重、腰围、臀围、血压,计算体重指数、腰臀比,检测空腹血糖(FBG)、ALT、GGT、甘油三酯、高密度脂蛋白胆固醇、脂联素、丙二醛(MDA)、还原型谷胱甘肽(GSH)和氧化型谷胱甘肽(GSSG)等指标。并分析血清脂联素与各临床指标的关系。结果:非酒精性脂肪肝患者血清脂联素水平明显低于正常对照组,氧化应激程度明显高于正常对照组;合并代谢综合征或肝功能异常的非酒精性脂肪肝患者氧化应激程度升高更显著,而脂联素水平下降更明显;血清脂联素水平与GSH、GSH/GSSG呈明显正相关,与ALT、AST、GGT、MDA、GSSG呈明显负相关;多重线性回归分析提示GSH/GSSG、GSSG、MDA、GSH、ALT是影响血清脂联素水平的独立相关因素。结论:脂联素可能是一种间接反映氧化应激程度的监测指标,脂联素、MDA及GSH/GSSG联合检测有助于非酒精性脂肪肝病情发展的判断。     

中医治疗非酒精性脂肪性肝病的思路

近年来我国非酒精性脂肪性肝病,在普通人群中发病率呈现逐年上升的趋势。本文从中医方向对非酒精性脂肪性肝病的病因、病机进行分析,并对非酒精性脂肪性肝病的中医治疗思路进行探讨。     

非酒精性脂肪性肝病无创诊断研究进展

非酒精性脂肪性肝病是全球最常见的慢性肝病。据估计,全球约25%的成年人患有非酒精性脂肪性肝病,且患病率逐年增加。非酒精性脂肪性肝病的疾病谱涵盖非酒精性脂肪肝、非酒精性脂肪性肝炎、非酒精性脂肪性肝炎相关纤维化、肝硬化和肝细胞癌。肝活检作为非酒精性脂肪性肝病诊断和分期的“金标准”,因有创性、取样变异和评价不一致等局限性限制了其广泛应用。随着进展为非酒精性脂肪性肝炎的患者数量增加,特别是疾病严重程度较重的病人增多,临床上迫切需要有效治疗药物,也迫切需要开发无创标志物来筛查、诊断、监测患者和判断疗效。对非酒精性脂肪性肝病的无创诊断研究进展进行综述,包括对脂肪变的评估、非酒精性脂肪性肝炎的诊断和纤维化的评估。     

CYP2E1介导的脂质过氧化在脂肪性肝病发病机制中的作用

脂肪性肝病包括酒精性脂肪性肝病和非酒精性脂肪性肝病,是由多种原因引起的肝脏脂蛋白代谢紊乱所致.细胞色素氧化酶P450的2E1亚型(CYP2E1)的个体差异大,具有基因多态性,其不仅参与了药物的代谢,而且还能催化乙醇、四氯化碳的代谢.CYP2E1氧化乙醇时产生活性氧是酒精性脂肪性肝病导致肝损伤的重要机制;在非酒精性脂肪肝的"两次打击学说"中,CYP2E1介导的脂质过氧化亦发挥重要的作用.通过对CYP2E1介导的脂质过氧化在脂肪性肝病发病机制中作用的进一步深入研究,有可能探索出有效治疗脂肪性肝病的新途径.     

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.