2型糖尿病血管内皮功能与胰岛素抵抗的关系研究

目的：了解2型糖尿病患者内皮功能损害的差异,并探讨其与胰岛素抵抗之间的关系。方法选择有或无血管并发症的2型糖尿病患者共88例,年龄、体重指数相匹配的健康对照44例。采用高分辨血管超声仪测定肱动脉血流介导的内皮依赖性血管舒张功能（ FMD）和硝酸甘油介导的非内皮依赖性血管舒张功能（ GTN）。同时测定受试者的血压、血糖、糖化血红蛋白、血脂及空腹C肽。结果（1）糖尿病组与对照组比较,胰岛素抵抗指数（ HOMA－CR）、收缩压、舒张压、空腹血糖、HbA1c、TC、TG、LDL－C均明显升高（P＜0．01或P＜0．05）,胰岛β细胞功能（HOMA－β）、HDL－C明显降低（P＜0．01）。在糖尿病2组之间,收缩压、舒张压、HbA1c、病程,有并发症组明显高于无并发症组（P＜0．01）,而HOMA－CR 2组之间无差异;HOMA－β有并发症组明显低于无并发症组（P＜0．01）。（2）糖尿病组的FMD和GTN明显低于对照组（P＜0．05或P＜0．01）,有血管并发症组更显著低于无并发症组（P＜0．01）。HOMA－CR与FMD和GTN存在负相关;HOMA－β与FMD和GTN存在正相关。基础血管内径三组间差异无显著性（P＞0．05）。结论2型糖尿病患者血管内皮功能明显降低,胰岛素抵抗是导致血管内皮功能障碍加重的危险因素。随着病程的延长,有血管并发症患者内皮功能降低更显著。     

妊娠糖尿病患者血浆 IL－1β水平变化与胰岛素抵抗的关系

目的：探讨妊娠糖尿病患者血浆白介素－1β（IL－1β）水平的变化及与胰岛素抵抗的关系。方法选取妊娠糖尿病组（GDM）65例,正常对照组（NC）55例,同时采集病史、进行体格检查并留取血浆,测定其空腹血糖、胰岛素、血脂和空腹 IL－1β的水平,采用 HOMA－IR 模型公式计算胰岛素抵抗指数,两因素间关系采用 Pearson 相关分析,多个变量间的分析采用多元逐步回归分析。结果 GDM 组 Fins、HOMA－IR 指数较 NC 组增高（ P ＜0．05）,HOMA－β指数较 NC 组降低（ P ＜0．05）,空腹血浆 IL－1β水平 GDM 组显著高于 NC 组（ P ＜0．01）;相关分析 HOMA－IR 指数与IL－1β、SBP、DBP、Fins、FPG、TC、TG、LDL－C 及 apo－B 呈正相关关系（ P ＜0．05）,与 HDL－C 呈负相关关系（ P ＜0．05）。校正 WHR 及 BMI 的影响后,HOMA－IR 指数与 IL－1β、DBP、Fins、FPG、TC、TG 及 LDL－C 呈正相关关系（ P ＜0．05）;与HDL－C 呈负相关关系（ P ＜0．05）。结论妊娠糖尿病患者血浆 IL－1β水平升高可间接反应胰岛素抵抗程度。     

肥胖儿童骨密度及胰岛素抵抗水平研究

目的探讨儿童肥胖与骨密度及胰岛素抵抗的关系。方法选取7～14岁肥胖儿童60例及正常体重儿童60例,使用超声骨密度仪测量桡骨远端超声波速度（SOS）,并抽血检测空腹血糖及胰岛素水平,采用胰岛素抵抗指数（HOMA—IR）评估胰岛素抵抗水平,比较两组骨密度及胰岛素抵抗水平的差异。结果肥胖儿童身高、体重、体重指数、腰臀比均显著高于正常儿童（P〈0．01）;肥胖儿童SOS高于正常儿童,差异有统计学意义（P〈0．05）;肥胖儿童HOMA—IR显著高于正常儿童（P〈0．01）。结论肥胖儿童骨密度及胰岛素抵抗水平高于正常体重儿童,减轻体重有利于改善胰岛素抵抗,但须注意科学方式,避免骨量减少。     

血压正常与非正常肥胖人群血管内皮功能和胰岛素抵抗的比较

目的探讨肥胖高血压发生与血管内皮功能和胰岛素抵抗（IR）的关系。方法肥胖高血压组病99例、单纯肥胖组91例及正常对照组87例，测定体质指数、空腹血糖、空腹胰岛素、HOMA-IR和血管内皮功能，进行组间比较，并对血压与其他各因素的关系进行多因素逐步回归分析。结果肥胖高血压组和单纯肥胖组反应性充血时血管内径显著低于正常对照组（P〈0．05～0．01），其中肥胖高血压组又低于单纯肥胖组（P〈0.05）。肥胖高血压组HOMA—IR显著高于单纯肥胖组和正常对照组（P〈0．01），而单纯肥胖组又高于正常对照组（P〈0．05）。收缩压与腰臀比、反应性充血血管内径、HOMA—IR显著相关（r=0．293，P〈0．01、r=-0．336，P〈0．01和r=0．193，P〈0．05），舒张压与腰围、反应性充血血管内径、空腹胰岛素、HOMA—IR显著相关（r分别为0．201、-0．256、0．311、0．284，均P〈0．01）。结论血管内皮功能障碍、IR及腹部脂肪增多是肥胖高血压发生的关键。     

初发2型糖尿病胰岛素强化治疗后胰岛β细胞功能变化

目的：用精氨酸-C肽刺激试验（AST）观察胰岛素强化治疗（IIT）对初发2型糖尿病胰岛J3细胞功能的影响以及CP峰值对选择治疗方案的指导价值。方法：50例新诊断的2型糖尿病患者（FPG〉11．1mmol·L-1）在饮食运动治疗的基础上给予胰岛素强化治疗2个月，分析治疗前后空腹血糖（FPG）、餐后2h血糖（P2hPG）、糖化血红蛋白（HbA1-C）、空腹胰岛素（FINS）、胰岛素分泌指数（HOMA-IS）、胰岛素抵抗指数（HOMA—IR）、体质量指数（BMI）、三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL—C）、高密度脂蛋白胆固醇（HDLC）及AST0，2，3，4，5min时血糖（PG）及C肽（CP）分泌的变化。结果：胰岛素强化治疗后，FPG、P2hPG、HbA1-C、HOMA-IR、TG、TC、LDLC较治疗前降低（P分别〈0．01，〈0．01，〈0．01，〈0．01，〈0．01，〈0．05，〈0．05）；HDL-C、HOMA—IS、FCP及精氨酸刺激后CP分泌较治疗前明显升高（P分别〈0．05，〈0．01，〈0．05，〈0．01）；FINS及BMI与治疗前相比变化不大（P〉0．05）。结论：胰岛素强化治疗通过改善初诊2型糖尿病的糖、脂毒性，能显著改善胰岛β细胞功能。精氨酸-C肽刺激试验安全、简便，可以反映胰岛口细胞的急性相分泌功能。对选择治疗方案具有一定的指导价值。     

慢性肾脏病与胰岛素抵抗相关性研究

目的探讨慢性肾脏病3—4期患者与稳态模型胰岛素抵抗指数（HOMA—IR）的相关性。方法选择住院治疗的56例CKD3—4期患者为慢性肾脏病组,健康体检人员35例为正常对照组（两组均除外糖尿病患者）。测量身高、体重、腰围、血浆葡萄糖、胰岛素、甘油三酯、总胆固醇、高密度脂蛋白胆固醇、超敏C反应蛋白和白细胞介素6,计算HOMA—IR。采用SPSS13．0软件包进行分析。结果慢性肾脏病组与正常对照组之间空腹胰岛素和HOMA—IR比较差异均有显著性意义（P〈0．01）。两组之间三酰甘油三酯、总胆固醇、高密度脂蛋白胆固醇、超敏C反应蛋白和白细胞介素6、腰围及体重指数均有明显差异（P〈0．05）。结论HOMA—IR是预测慢性肾脏病患者胰岛素抵抗的独立影响因子,减轻胰岛素抵抗可保护肾功能。     

2型糖尿病患者非糖尿病一级亲属胰岛素抵抗与脂代谢紊乱

目的：探讨2型糖尿病患者非糖尿病一级亲属（简称一级亲属）胰岛素抵抗及其脂代谢紊乱。方法：以一级亲属55例为观察组，42例性别、年龄、体重指数（BMI）与之相匹配的无糖尿病家族史的正常人为对照组，比较两组口服75g葡萄糖耐量试验（OGTT）中0、60、90、120分钟血糖、胰岛素（INS）、C－肽（CP）及空腹血脂。结果：（1）一级亲属组较正常对照组0点胰岛素和C－肽以及稳态模型法（HOMA）计算的胰岛素抵抗指数（HOMA－IR）显著性升高。一级亲属组空腹甘油三酯（TG）升高，而高密度脂蛋白胆固醇（HDL－C）降低，两组有显著性差异（2）一级亲属BMI＜23，23≤BMI＜25，BMI≥25三个亚组比较0点血糖无差异，而60、90、120分钟三点血糖，0，60、90、120分钟胰岛素，C－肽、HOMA－IR随BMI的增加而增加，且有显著性差异，三个亚组之间血脂比较总胆固醇（TC）和TG亦有显著性差异。（3）TG与空腹INS、C－肽、HOMA－IR呈显著正相关。一级亲属HOMA－IR与BMI、TG、空腹INS、C－肽呈显著正相关。结论：2型糖尿病患者非糖尿病一级亲属在血糖正常时已存在在高胰岛素血症，胰岛素抵抗，同时伴有高TG，低HDL－C血症等脂代谢紊乱。一级亲属中，随着体重的增加胰岛素抵抗和脂代谢紊乱更趋严重。     

2型糖尿病患者血清Apelin与VCAM-1的关系

目的研究2型糖尿病（T2DM）患者血浆Apelin与血管细胞问黏附分子-1（VCAM-1）的水平,探讨Apelin与VCAM-1、高胰岛素血症、肥胖及糖脂代谢等的相关性。方法采用酶联免疫吸附法测定r12DM患者和正常糖调节（NGR）人群空腹血浆Apelin、VCAM．1水平及测定身高、体重、空腹血清胰岛素（Fins）、空腹血糖（FBG）、三酰甘油（TG）、总胆固醇（TC）指标,计算体重指数（BMI）、胰岛素抵抗指数（HO—MA—IR）及胰岛p细胞功能指数（HOMA—p）。结果2型糖尿病患者血浆Apelin、VCAM．1均高于正常对照组（P〈0．01）。相关分析显示：血浆Apelin与FBG（r=0．587,P〈0．01）、FINs（r=0．632。P〈0．01）、BMI（r=0．564,P〈0．01）、TG（r=0．385,P〈0．05）、1、C（r=0．467．P〈0．05）、HOMA．IR（r=0．667,P〈0．01）、VCAM-1（r=0．701,P〈0．01）呈正相关,与HOMA．B呈负相关（r=-0．567,P〈0．01）。多元逐步回归分析,表明VCAM-1是Apelin的独立相关因素（R2VCAM-1=0．686,P〈0．01）。结论血浆Apelin和VCAM-1水平在2型糖尿病患者中升高,Apelin与VCAM-1、高胰岛素血症、肥胖、糖脂代谢相关,VCAM-1水平是Apelin独立相关因素,推测Apelin与血管内皮功能受损有关。     

2型糖尿病合并非酒精性脂肪肝与胰岛素抵抗及血脂紊乱关系研究

目的探讨2型糖尿病（T2DM）合并非酒精性脂肪肝（NAFLD）与胰岛素抵抗（IR）、血脂紊乱的关系。方法对38例T2DM合并NAFLD患者进行血脂、血糖、血压、空腹及餐后2h血浆胰岛素（Fins、2hlns）的测定，计算胰岛素抵抗指数（HOMA．IR）、体重指数（BMI）、腰臀比（WHR），并与34例非脂肪肝糖尿病患者作比较。结果脂肪肝组甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、Fins、2hlns、HOMA．IR、BMI、WHR、ALT、γ-谷氨酰转肽酶、尿酸、舒张压的平均水平均较非脂肪肝组明显升高（P〈0．05～0．01），高密度脂蛋白胆固醇水平明显降低（P〈0．05）。两组血糖、糖化血红蛋白水平差异无统计学意义（P〉0．05）。结论T2DM合并NAFLD较未并发脂肪肝患者存在明显的IR、脂质代谢异常及肥胖，提示IR在脂肪肝的发病中具有十分重要的地位；NAFLD可能是代谢综合征的一个组成部分。     

2型糖尿病患者医源性高胰岛素血症与血糖波动的关系及相关因素研究

目的 研究医源性高胰岛素血症与糖化血红蛋白及血糖之间的关系.方法 186例2型糖尿病患者分成高胰岛素血症组96例和正常胰岛素组90例,比较2组临床资料、血糖、胰岛素、C肽、糖化血红蛋白,并利用空腹C肽值计算稳态HOMA胰岛素抵抗指数和HOMA-β细胞分泌指数.结果 2组临床资料比较差异无统计学意义（P〉0 05）;高胰岛素组空腹血糖、餐后血糖、空腹胰岛素、餐后胰岛素、空腹C肽、餐后C肽以及糖化血红蛋白较正常胰岛素组明显升高,稳态HOMA胰岛素抵抗指数和HOMAβ细胞分泌指数高于正常胰岛素组,差异均有统计学意义（P〈0.05）.结论 医源性高胰岛素血症所引起的血糖波动,系医源性胰岛素诱发的胰岛素抵抗,对β细胞分泌影响并不明显.     

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.