2型糖尿病颈动脉内膜中层厚度与胰岛素抵抗的关系

目的探讨2型糖尿病患者颈动脉内膜增生与胰岛素抵抗的关系。方法采用超声测定127例2型糖尿病患者颈动脉内膜中层厚度（IMT）,根据IMT分为IMT正常组（IMT≤0.9mm）38例、IMT增厚组⑴（0.9mm〈IMT〈1.3mm）44例和IMT增厚组⑵（IMT≥1.3mm）45例。所有受试者测量身高、体质量,计算体质量指数（BMI）,同时测定并比较两组空腹血糖（FPG）、空腹胰岛素（FIns）、尿酸（UA）、超敏C反应蛋白（hs-CRP）、甘油三酯（TG）、总胆固醇（TC）,低密度脂蛋白（LDL-C）、高密度脂蛋白（HDL-C）,计算稳态模型胰岛素抵抗评估指数（HOMA-IR）。结果2型糖尿病患者颈动脉IMT增厚主要与年龄、病程、FIns和HOMA-IR有关。IMT增厚组⑵FIns和HOMA-IR显著高于IMT正常组,并高于IMT增厚组⑴,并且胰岛素抵抗程度和代偿性高胰岛素血症程度与IMT的增厚呈正相关。结论胰岛素抵抗可能与2型糖尿病颈动脉内膜增厚有关。     

罗格列酮联合胰岛素治疗2型糖尿病的临床观察

目的探讨罗格列酮联合胰岛素治疗单用胰岛素血糖控制不佳的2型糖尿病患者的临床疗效。方法将62例单用胰岛素、体质指数（BMI）≥25、血糖控制不理想的2型糖尿病患者随机分成2组：（胰岛素＋罗格列酮）组32例，在使用胰岛素的基础上联合罗格列酮4mg／d口服，并根据血糖水平适时调整胰岛素用量；胰岛素组30例，继续应用胰岛素治疗。观察治疗前、治疗后4周、8周、12周2组患者的空腹血糖（rBG）、餐后2h血糖（2hPG）、空腹c肽（FCP）、餐后2hC肽（2hCP）、糖化血红蛋白（HbA，C）、胆固醇（TC）、甘油三脂（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、尿微量白蛋白／肌酐（A／C）、BMI、胰岛素用量的改变。结果治疗后4、8、12周时，2组血糖、HBA，C均下降；4周时，2组胰岛素用量均增加；8周时，2组BMI增加、TG下降，2组间同期比较差异无统计学意义，组内治疗前后比较差异均有统计学意义（P〈0.05或0.01）；治疗8周时，（胰岛素＋罗格列酮）组胰岛素用量减少，而胰岛素组用量继续增加，治疗12周时，2组TC、TG下降，（胰岛素＋罗格列酮）组胰岛素用量进一步减少、A／C、2hCP下降，I-IDL-C升高，组间同期及组内治疗前后比较均有统计学意义（P〈0．05或P〈0．01）。结论胰岛素治疗血糖控制不理想的2型糖尿病患者加用罗格列酮可使血糖得到良好控制，减少胰岛素剂量，改善代谢综合征的一系列异常，治疗安全有效。     

代谢综合征、C反应蛋白与冠心病关系的临床研究

目的：探讨代谢综合征（MS）、C反应蛋白与冠心病之间的关系。方法：将230例MS患者分为MS合并冠心病组和MS无冠心病组，比较其体重指数（BMD、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋自（LDL）、高密度脂蛋白（HDL）、空腹血糖（FBG）、餐后2小时血糖（2hBG）、空腹胰岛素（FINS）、餐后2小时胰岛素（2hINS）、糖化血红蛋白（HbAlc）及胰岛素抵抗指数（ISI）、C反应蛋白（CRP）的变化。结果：MS患者BMI、TG、TC、LDL、FBG、2hBG、FINS、2hINS、HbAlc、CRP较对照组显著升高（P〈0．01），ISI较对照组显著降低（P〈0．01），而MS合并冠心病组较无冠心病组上述改变更显著（P〈0．05）。结论：MS患者存在血脂和血糖代谢紊乱、胰岛素抵抗和炎症标记物CRP升高的病理变化，胰岛素抵抗和炎症状态在MS患者冠心病的发生和发展起着促进作用。     

罗格列酮增强胰岛素抵抗大鼠胰岛素敏感性作用

目的：研究罗格列酮对多种胰岛素抵抗（insulin resistance，IR）大鼠模型的作用。方法：分别建立2型糖尿病（T2DM）伴IR、高脂血症-IR、地塞米松（DX）诱导IR大鼠3种动物模型，观察罗格列酮对病鼠给药后2h血糖（FBG）、口服葡萄糖耐量试验（OGTT）后2h血糖（2hBG）以及给药后2h空腹血清血糖（FSG）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白-胆固醇（HDL-C）、低密度脂蛋白-胆固醇（LDLC）、丙二醛（MDA），肿瘤坏死因子-α（TNF-α），胰岛素（Fins）含量及胰岛素敏感指数（ISI），超氧化物歧化酶（SOD）活性等指标的影响。结果：罗格列酮显著降低病鼠FSG，TC，TG，LDL-C和Fins、TNF-α的浓度（P〈0．05），显著提高HDL—C含量及ISI（P〈0．05）．增强胰岛素敏感性。加强SOD活性和降低MDA的含量（P〈0．05），增强抗氧化能力。结论：罗格列酮能调整各动物模型所致的糖脂代谢障碍，纠正高脂血症及高胰岛素血症，拮抗病鼠限，改善其胰岛素敏感性，增强抗氧化作用。     

马来酸罗格列酮对高果糖餐大鼠胰岛素抵抗的影响

目的观察马来酸罗格列酮对高果糖餐大鼠胰岛素抵抗的影响。方法6SD大鼠45只，予普通饲料喂养4周后，将其随机分为正常对照组、模型对照组和试验组，各15只。正常对照组继续以普通饲料喂养；另2组以高果糖餐喂养4周后，试验组用马来酸罗格列酮治疗4周；用tail—cuff法测定收缩期血压（SBP）；用正常血糖高胰岛素钳夹技术评价胰岛素敏感性。结果4，8周时，试验组和模型对照组的收缩压较正常对照组显著增高（P〈0．05）；而体质量较正常对照组显著下降（P〈0．05）。游离脂肪酸、空腹胰岛素、胰岛素敏感指数：试验组较模型对照组有显著改善（P〈0．05，0．01）。结论马来酸罗格列酮可显著改善高果糖餐大鼠的胰岛素抵抗；降低内源性胰岛素及游离脂肪酸和甘油三酯水平，并对血压降低有一定影响。     

罗格列酮钠联合二甲双胍改善2型糖尿病患者糖脂代谢及机制研究

目的探讨罗格列酮钠联合二甲双胍治疗对2型糖尿病患者糖脂代谢及胰岛素抵抗改变及其作用机制。方法 42例确诊2型糖尿病患者经过二甲双胍及罗格列酮钠干预治疗12周。检测治疗前后空腹血糖(FBS)、餐后2h血糖(PBS)、空腹胰岛素(FINS)、血清总胆固醇(TC)、三酰甘油(TG)低密度胆固醇(LDL)等血脂全套,用HOMA公式计算胰岛素抵抗指数(IR)与正常对照组34例相比较。同时测定治疗前后血清游离脂肪酸(FFA)、C反应蛋白(CRP)。结果 2型糖尿病患者与对照组比,FBS、PBS、HbA1c、LDL、TC、TG、FFA、CRP、IR均显著增高。2型糖尿病组经干预治疗后,FBS、PBS、HbA1c、IR、FFA、CRP浓度均比治疗前显著下降(P<0.01)。LDL、TC、TG经治疗后亦有明显下降(P<0.01)。结论罗格列酮钠联合二甲双胍治疗肥胖2型糖尿病患者可通过降低CRP、FFA,改善IR从而改善糖脂代谢。     

罗格列酮治疗非酒精性脂肪肝病的疗效观察

目的观察胰岛素增敏剂罗格列酮对非酒精性脂肪肝病（NAFLD）的治疗效果。方法124例NAFLD患者,应用罗格列酮治疗。治疗6个月后,检测患者治疗前后的体质量（W）、腰臀比（WHR）、体重指数（BMI）、空腹血糖（FPG）、空腹血胰岛素（FINS）、血总胆固醇（TC）、血甘油三酯（TG）、谷草转氨酶（AST）、谷丙转氨酶（ALT）、1-谷氨酰转移酶（GGT）及胰岛素抵抗指数HOMA-IR。根据症状、体征、肝脏B超和cT表现及各项生化检查结果综合判断各组患者的治疗效果。结果治疗组患者的2hPG、FPG,FINS、HOMA．IR2hPINS、ALT、HOMA．IR,TG均较治疗前明显改善,差异有统计学意义。结论罗格列酮治疗NAFLD安全有效,     

影响颈动脉内膜中层厚度的代谢因素分析

目的 探讨影响颈动脉内膜中层厚度(IMT)的代谢因素.方法 根据IMT将194例患者分为三组:A组,68例,IMT 0.7mm～;B组,66例,IMT0.9mm～;C组,60例,IMT≥1.1 mm.检测血清脂联素(APN)、空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、空腹胰岛素(FIns),计算体重指数(BMI)、腰臀比(WHR)和胰岛素抵抗指数(HOMA-IR).结果 WHR、FBG、FIns、TC、TG和HOMA-IR与IMT呈正相关(P＜0.01),而与APN呈负相关(P＜0.05);APN与IMT呈明显负相关(r=-0.432,P＜0.01).结论 FBG、TC、TG、HOMA-IR、APN与IMT明显相关;APN与IMT呈明显负相关,可以作为动脉粥样硬化的检测指标.     

罗格列酮治疗非酒精性脂肪肝的初步研究

目的评价罗格列酮对非酒精性脂肪肝（NAFLD）的作用,观察其疗效。方法选择60例NAFLD患者随机分组,对照组30例,罗格列酮组30例,观察体重指数（BMI）、空腹血糖（FBG）、空腹胰岛素含量（FINS）、胰岛素抵抗指数（HOMA-IR）、三酰甘油（TG）、总胆固醇（TC）、谷丙转氨酶（ALT）、谷草转氨酶（AST）等变化。并比较治疗前后肝脾CT比值改变,比较两组疗效。结果与对照组对比,罗格列酮组治疗后,FPG、FINS、HOMA—IR、TC、TG、ALT、AST明显降低,肝脾CT比值明显升高,均有统计学意义（P〈0．05）。结论罗格列酮能改善NAFLD患者的血糖和血脂,改善胰岛素抵抗,逆转肝脂肪变性和NAFLD所致的肝脏酶谱升高。     

胰岛素抵抗与动脉粥样硬化

目的：探讨胰岛素抵抗与动脉粥样硬化的关系。方法：根据用稳态模型计算出的胰岛素抵抗指数(HOMA-IR)将221例患者分为5组，进行口服75g葡萄糖耐量试验，检查血脂及胰岛素水平，B型超声检查双侧颈总动脉内中膜厚度(IMT)，比较各组的危险因素及颈动脉粥样硬化指标。结果：随着HOMA-IR值升高，糖耐量低战、糖尿病、高血压和冠心病发病率增高，甘油三酯(TG)、低密度脂蛋白(LDL)、空腹血糖、服糖后2h血糖和空腹胰岛素水平增高，高密度脂蛋白(HDL)水平降低，IMT值升高。多元回归分析结果显示，TG、胆固醇、HDL、LDL、Ln(HOMA-IR)与IMT独立相关，是IMT增高的危险因素。结论：胰岛素抵抗参与动脉粥样硬化的形成。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.