肾组织中降钙素基因相关肽与糖尿病大鼠早期肾损害的相关性研究

目的：观察糖尿病大鼠肾组织中CGRP的含量变化与24h尿微量白蛋白的关系，为早期防治DN提供理论依据。方法：Wistar大鼠，体重160-200g，于造成糖尿病大鼠模型后第6、8、10、12、14周测定肾组织中的CGRP和24h尿微量白蛋白。结果：肾组织中的CGRP在造模后第6周无明显改变，第8周开始呈进行性下降，并与24h尿微量白蛋白呈显著负相关。结论：动态观察肾组织中CGRP的变化对于DN的早期发现及分析病情有重要意义。     

血浆中降钙素基因相关肽与糖尿病大鼠早期肾损害的相关性研究

目的：观察糖尿病大鼠血浆中CGRP的含量变化与24h尿微量白蛋白的关系，为早期防治DN提供理论依据。方法：Wistar大鼠，体重160-200g，于造成糖尿病大鼠模型后第6、8、10、12、14周测定血浆中的CGRP和24h尿微量白蛋白。结果：血浆中的CGRP在造模后第6周无明显改变，第8周开始呈进行性下降，并与24h尿微量白蛋白呈显著负相关，结论：动物观察血浆中CGRP的变化对于DN的早期发现及分析病情有重要意义。     

羟苯磺酸钙对早期糖尿病肾病大鼠肾脏的保护作用

用腹腔注射链脲佐菌素（streptozotocin,STZ）的方法制备大鼠糖尿病模型,观察羟苯磺酸钙对大鼠早期糖尿病肾病的肾脏保护作用。雄性Wistar大鼠随机分为正常对照组、DN空白对照组、羟苯磺酸钙75、150及300 mg·kg^-1组、培哚普利0.4 mg·kg^-1组。给药8周。动态检测各组大鼠血糖、24 h尿白蛋白,末次给药后测定大鼠糖化血红蛋白（HbA1c）,用放射免疫法测定血浆及肾皮质内皮素（ET）含量,用免疫组化技术检测肾皮质纤溶酶原激活物抑制剂-1（PAI-1）、基质金属蛋白酶-9（MMP-9）的表达,光镜、电镜下观察肾脏病理形态的改变。结果显示：羟苯磺酸钙能降低早期DN大鼠24 h尿白蛋白及血浆和肾皮质ET水平,降低肾脏局部PAI-1表达,升高MMP-9表达。羟苯磺酸钙可以保护血管内皮,抑制肾脏纤维化,减轻肾脏病理损伤,从而保护大鼠肾脏功能。     

糖肾宁对糖尿病肾病大鼠血浆ET、CGRP含量的影响

目的探讨糖肾宁对糖尿病大鼠血中内皮素(ET)降钙素基因相关肽(CGRP)的影响。方法采用反复多次小剂量腹腔注射链脲佐菌素(STZ)的方法建立糖尿病大鼠模型,随机分为正常组、糖尿病模型组、糖肾宁治疗组、糖肾宁+胰岛素(RI)组、胰岛素(RI)组和福辛普利组,观察8周后检测各组大鼠血糖、24h尿微量白蛋白排泄量(24hU-Alb)的变化,采用放射免疫法检测大鼠血浆ET、CGRP的表达。结果糖尿病模型组大鼠血糖、24hU-Alb经糖肾宁治疗后,上述指标均有下降(P<0.01或P<0.05模型组CGRP表达高于正常组,经药物治疗8周后,CGRP表达上升,ET各组无明显差异。结论糖肾宁可通过调节大鼠血流动力学改变,达到保护肾脏的作用。     

赖诺普利联合杏丁治疗早期糖尿病肾病疗效观察

目的：观察赖诺普利联合杏丁治疗早期糖尿病肾病（DN）之疗效，比较治疗前后24小时尿微量白蛋白（u-MA）的变化。方法：选择36例糖尿病合并早期DN的住院患者，随机分为治疗组和对照组，在控制血糖的同时，治疗组给予杏丁20ml静脉滴注，每日1次，以及赖诺普利2．5mg／d，晨起时顿服，疗程2周。对照组给予一般治疗。结果：上述两种药物联合使用能有效控制早期DN患者尿微量白蛋白的进行性升高。治疗2周后u-MA从137mg／24h下降至74mg/24h（P〈0．01）。结论：两种药物联合应用对于降低早期DN患者的u-MA有明显疗效。     

福辛普利联合前列地尔治疗早期糖尿病肾病临床观察

目的:观察福辛普利联合前列地尔注射液治疗早期精尿病肾病(DN)24h尿微量白蛋白、血肌酐水平的影响.方法:将48例早期DN患者随机分为两组,治疗组给予福辛普利口服联合前列地尔注射液静脉给药,对照组给予福辛普利口服,治疗时间均为4周,比较治疗前后24h尿微量白蛋白量、血肌酐水平的变化.结果:两组治疗后尿微量白蛋白排除率较治疗前均显著下降,治疗组疗效优于对照组(P<0.01).结论:福辛普利联合前列地尔治疗早期糖尿病肾病能显著降低尿白蛋白排出量.     

冬虫夏草对大鼠糖尿病肾病的保护作用机制研究

目的：观察人工冬虫夏草制剂对链尿佐菌素（STZ)诱导的糖尿病肾病（DN）大鼠肾组织转化生长因子（TGF-β1)和结缔组织生长因子（CTGF）表达的影响,探讨虫草制剂对糖尿病肾病的肾保护和抗纤维化机制。方法将36只Wistar雄性大鼠,随机分为对照组（12只）,24只成模组随机分为DN模型组,虫草组,虫草组予400mg/(kg·d)灌胃给药,分别于第2、4、8周处死大鼠（每组4只）分别检测血糖值、体重、24h 尿微量蛋白、肌酐（Scr）含量、肾脏的病理变化,免疫组化法检测肾脏中TGF-β1和CTGF的表达。结果 DN模型组大鼠尿微量白蛋白排泄率显著增加（P<0.01）现高表达。虫草治疗组与DN模型组比较,虫草治疗组尿微量蛋白排泄率显著减少（P<0.01)Scr 水平降低(P<0.01),肾组织病理改变减轻,肾组织内TGF-β1和CTGF表达下调（P<0.05或P<0.01)。结论虫草制剂对DN具有肾脏保护作用,其机制可能是通过使TGF-β1/CTGF的表达下调而实现的。     

小檗碱对早期糖尿病肾病大鼠肾组织病理变化与BMP-7蛋白及mRNA表达的影响

目的:研究小檗碱(BBR)对糖尿病肾病(DN)大鼠肾组织病理变化与骨形成蛋白-7(BMP-7)蛋白及mRNA表达的影响,探讨BBR对DN大鼠早期肾脏损伤的作用及其可能机制。方法:以链脲佐菌素(STZ)复制早期DN大鼠模型,动物分为正常对照组、模型组、3个BBR(50,100,200 mg.kg-1)治疗组及依那普利(1 mg.kg-1)治疗组,灌胃给药,qd,5周后检测各组大鼠尿量、左肾重、肾重/体重比值;生化指标检测空腹血糖(FBG)、尿素氮(BUN)、血肌酐(Scr)、胰岛素(Ins)、24 h尿蛋白量(Upro)及24 h尿微量白蛋白(Um-Alb);光镜和电镜观察肾组织形态学和超微结构的改变;免疫组化技术和逆转录聚合酶链反应(RT-PCR)检测肾组织BMP-7蛋白和mRNA表达。结果:与模型组比较,BBR各治疗组DN大鼠FBG,BUN,Scr,Upro及UmAlb水平降低,Ins升高;肾组织形态学异常和超微结构病变改善;BMP-7蛋白和mRNA表达增多。结论:BBR可显著升高早期DN大鼠肾组织BMP-7蛋白及mRNA的表达,改善早期DN大鼠肾功能病变,延缓DN发展。     

牛膝多糖对糖尿病肾脏保护作用的研究

目的:观察牛膝多糖对实验性糖尿病(DM)大鼠肾脏的保护作用及对转化生长因子-β1(TGF-β1)表达的影响.方法:用链尿佐菌素(STZ)诱发、建立糖尿病大鼠模型,通过牛膝多糖干预治疗,观察糖代谢(血糖、胰岛素)、肾功能、血及肾组织的TGF-β1表达等指标的变化.结果:①牛膝多糖治疗组与糖尿病未治疗组比较明显降低DM大鼠血糖、尿素氮、尿总蛋白(24h)及微量白蛋白,升高胰岛素水平,抑制肾皮质TGF-β1表达.②肾脏TGF-β1表达量与尿总蛋白(24 h)、尿白蛋白(24 h)浓度呈显著正相关.结论:牛膝多糖具有减少尿微量白蛋白排出、血尿素氮浓度、减少肾脏TGF-β1表达的作用;牛膝多糖有防治糖尿病肾病(DN)的作用,其防治DN及保护肾功能的作用与其降低肾脏TGF-β1表达有关.     

替米沙坦治疗早期糖尿病肾病疗效观察

目的 观察替米沙坦治疗早期糖尿病肾病(DN)的临床疗效.方法 选择本院门诊及住院的38例早期DN患者随机分为治疗组和对照组,对照组给予正规糖尿病治疗8周,治疗组加服替米沙坦80mg每日1次,比较两组治疗前后24h尿微量白蛋白排泄量.结果 治疗组尿微量白蛋白下降比对照组有显著差异(P＜0.01).结论 替米沙坦降早期糖尿病肾病尿微量白蛋白效果明显,且无明显副作用,能保护肾功能,延缓肾功能不全的发生.     

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.