2型糖尿病大鼠肾脏转化生长因子-β1Ⅳ型胶原和细胞间黏附分子-1表达的变化

<正>糖尿病肾病(diabetic nephropathy,DN)是糖尿病患者常见并发症,也是糖尿病患者死亡的主要原因之一。DN典型的病理改变是肾小球硬化,其组织学特征是肾小管和肾小球基底膜增厚,系膜基质扩张、肾肥大以及肾小管间质纤维化[1]。许多学者已证明转化生长因子(TGF)-β1为致纤维化因子,其表达增多可指导细胞外基质(ECM)的生成,并抑制其降解,在DN发病机制的各个环节起着重要的作用。Ⅳ型胶原的合     

糖尿病肾病早期诊断指标的研究与进展

糖尿病肾病(diabetic nephropathy,DN)是糖尿病常见的慢性并发症,由糖尿病微血管病变引起,以肾小球硬化为主要病理特征,伴或不伴肾小管和肾间质病变.大约40％的1型和2型糖尿病患者可并发DN.DN起病隐匿,因此有一相当长的无症状期[1],早期诊断DN可以达到早期干预,延缓DN发展的目的.本文就与糖尿病肾病相关的生化指标在早期诊断DN方面的研究作一综述.     

单核细胞趋化蛋白-1和Ⅳ型胶原在糖尿病肾病大鼠肾组织中的表达

目的观察单核细胞趋化蛋白-1(MCP-1)、Ⅳ型胶原(Ⅳ-C)在链尿佐菌素诱发的糖尿病肾病(DN)大鼠肾组织中的表达;探讨洛汀新、来氟米特、来适可对DN大鼠肾组织中MCP-1、Ⅳ-C表达的影响。方法将大鼠随机分成五组:正常组(C组)、糖尿病肾病组(D组)、糖尿病肾病洛汀新治疗组(DL组)、糖尿病肾病来氟米特治疗组(DF组)和糖尿病肾病来适可治疗组(DK组)。6周后,用免疫组化方法测定各组肾组织中MCP-1、Ⅳ-C的表达。结果MCP-1在DN大鼠肾小球、肾小管中的表达增高。Ⅳ-C在DL组肾小球中的表达与C组比较差异无显著性,在各治疗组与D组肾小管中的表达差异有显著性(P<0.01)。结论 MCP-1、Ⅳ-C在DN大鼠肾组织中表达增高;洛汀新、来氟米特、来适可能下调MCP-1在DN大鼠肾小球、肾小管中的表达;洛汀新可明显下调Ⅳ-C在DN大鼠肾小球中的表达。     

结缔组织生长因子在糖尿病肾病发生发展中的作用

目的 动态观察大鼠糖尿病肾病(DN)的不同阶段肾皮质结缔组织生长因子(CTGF)表达的变化及其与肾功能及肾组织形态学变化的相关性,探讨尿液中CTGF含量的检测作为DN诊断指标的意义.方法 以链脲佐菌素(STZ)诱导糖尿病大鼠为研究对象.63只大鼠分为糖尿病组33只和对照组30只.应用逆转录聚合酶链反应、免疫组织化学及蛋白质印迹法研究在糖尿病的不同时期肾皮质CTGF表达的动态变化,并研究其与DN早期肾肥大、ECM的聚积及后期肾小球硬化及肾间质纤维化之间的关系,同时以ELISA法检测糖尿病大鼠尿液中CTGF含量.结果 糖尿病大鼠肾皮质mRNA及CTGF蛋白质表达2周时开始增加,12周时达高峰,分别为(0.905±0.028)、(0.802±0.028),为正常对照组的4.38倍和9.97倍(均P＜0.05);其表达早期出现在肾小球,而后随着病程的发展出现于肾小管间质区域.相关性分析显示CTGF的表达与肾指数、肾小球体积、系膜基质指数、肾小管间质纤维化程度呈正相关(均P＜0.01);糖尿病大鼠尿液中CTGF的含量随着病程的发展逐渐升高,最高为(277.679±10.372)ng/L,与24h尿微量白蛋白、BUN、Cr呈正相关(均P＜0.01).结论 CTGF表达的增加贯穿了DN发病的整个过程,早期介导了肾肥大,肾小球ECM的积聚,晚期又介导了肾小球硬化及肾小管间质纤维化的发生;尿液CTGF的检测可以作为DN诊断的一个指标.     

胰岛素泵与多次胰岛素皮下注射对2型糖尿病肾病患者血糖波动的影响

<正>目前,糖尿病已经成为主要威胁公众健康的疾病之一,其最不利的并发症是糖尿病肾病(DN),DN是糖尿病患者合并有肾小球硬化、肾动脉硬化及肾盂肾炎的合称,病变累及肾小球、肾小动脉、肾小管及间质组织,临床上以持续白蛋白尿为主要特征,伴有肾小球滤过率进行性下降导致终末期肾     

厄贝沙坦治疗早期糖尿病肾病的疗效观察

糖尿病肾病(DN)是糖尿病最严重的慢性并发症之一,是导致终末期肾病的主要原因[1]。DN的病理改变其主要特征为肾小球基底膜增厚,早期临床表现为尿微量白蛋白增高[2]。近年来对DN的深入研究发现,RAS系统在DN的发生发展中起重要     

芪地归芎汤对早期糖尿病肾病肾小管功能的影响

<正>糖尿病肾病(DN)是糖尿病常见而严重的微血管并发症,患者在早期若得不到适当治疗,常发展至终末期肾功能衰竭,是糖尿病患者的主要死亡原因之一。在以往的研究中,侧重于关注肾小球病变,而忽视了小管间质的损害。最近研究认为糖尿病在肾小球滤过膜发生变化的同时甚或之前,小管间质已发生病变[1]。且同原发性肾小球疾病一样,其改变不仅是早期肾损害标志,而且与肾功能及预后密切相关[2]。我们观察了芪地归芎汤对早期糖尿病肾病(EDN)患者肾小管功能的影响,了解其对EDN患者肾小管的保护作用。     

纤溶酶原激活物及其抑制剂-1与肾间质纤维化

肾间质纤维化(RIF)几乎是所有慢性肾脏疾病进展到后期的最终结果[1]。无论肾脏病原发病因和部位在肾小球、肾小管还是肾血管,大多数进展性肾病均可见到肾小管间质纤维化。大量研究表明,RIF的程度与肾功能的相关性比肾小球硬化与肾功能的相关性更为密切,因此RIF越来越被人们所重     

内皮素和一氧化氮与糖尿病肾病关系的研究进展

糖尿病肾病(diabetes nephropathy,DN)是糖尿病(DM)微血管主要的并发症之一,可致终末期肾病(EsRD)。体内代谢紊乱、细胞因子等的综合作用可致DN的发生[1],其中血管舒缩失调与血管活性物质浓度异常密切相关,是肾血流动力学紊乱的关键。DN患者肾脏微血管病变的发生发展与血管内皮细胞损伤、血小板活化、纤溶活性降低密切相关。DN早期肾小球内皮细胞功能即可出现异常[2],这与DN肾小球内高压力、高灌注及肾小     

多项指标对早期糖尿病肾病诊断效能的评价

<正>糖尿病是以慢性血糖升高为特征的代谢性疾病,长期存在的高血糖,可能引起眼、肾、心脏、血管、神经的慢性损害或功能障碍。其中,糖尿病肾病(diabetic nephropathy,DN)是慢性糖尿病最严重的并发症之一,主要病理改变为肾小球基底膜增厚及系膜区细胞外基质沉积,肾小球硬化,引起蛋白尿,最终导致肾功能衰竭。约20%~40%的糖尿病患者可能发展为DN,40%终末期肾病的患者可能发生死亡[1]。因此,对DN     

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.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

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.