替米沙坦对胰岛素抵抗大鼠体质量及糖脂代谢的影响

目的 探讨替米沙坦对胰岛素抵抗(IR)大鼠体质量及糖脂代谢的影响.方法 30只雄性SD大鼠随机分为对照组(10只)和高脂组(20只),分别给予普通饲料喂养和高脂饲料喂养(制备IR大鼠模型)8周.8周后高脂组大鼠再随机分为模型组(9只)和替米沙坦干预组(9只).随后替米沙坦干预组大鼠给予替米沙坦5mg/kg灌胃,其余两组则给予等量0.9%氯化钠注射液灌胃,6周后分别测定体质量(BW)、血脂[总胆固醇(TC)、三酰甘油(IC)]、游离脂肪酸(FFA)、空腹血糖(FBG)、胰岛素(FINS)等指标,计算胰岛素敏感指数(ISI).结果 与模型组比较,替米沙坦治疗后大鼠的体质量、附睾脂肪重量、TC、TG、FFA、FINS显著降低,而ISI显著增加,差异有统计学意义(P＜0.05).结论 替米沙坦能减轻IR大鼠的体质量和内脏脂肪重量,改善糖脂代谢紊乱,提高胰岛素敏感性.     

替米沙坦对胰岛素抵抗大鼠体质量及糖脂代谢的影响

目的探讨替米沙坦对胰岛素抵抗(IR)大鼠体质量及糖脂代谢的影响。方法 30只雄性SD大鼠随机分为对照组(10只)和高脂组(20只),分别给予普通饲料喂养和高脂饲料喂养(制备IR大鼠模型)8周。8周后高脂组大鼠再随机分为模型组(9只)和替米沙坦干预组(9只)。随后替米沙坦干预组大鼠给予替米沙坦5mg/kg灌胃,其余两组则给予等量0.9%氯化钠注射液灌胃,6周后分别测定体质量(BW)、血脂[总胆固醇(TC)、三酰甘油(TG)]、游离脂肪酸(FFA)、空腹血糖(FBG)、胰岛素(FINS)等指标,计算胰岛素敏感指数(ISI)。结果与模型组比较,替米沙坦治疗后大鼠的体质量、附睾脂肪重量、TC、TG、FFA、FINS显著降低,而ISI显著增加,差异有统计学意义(P<0.05)。结论替米沙坦能减轻IR大鼠的体质量和内脏脂肪重量,改善糖脂代谢紊乱,提高胰岛素敏感性。     

氨氯地平对高血压伴胰岛素抵抗大鼠血清脂联素的影响

目的：观察氨氯地平对高血压伴胰岛素抵抗动物模型血清脂联素浓度的影响。方法：6周龄的雄性Wistar大鼠随机分为4组（每组10只,均以普通标准饲料）。对照组以普通自来水喂养;果糖组（F组）及氨氯地平治疗组以10/果糖水喂养;氨氯地平组分低剂量组（L组）和高剂量组（H组）,果糖水喂养8周后分别以不同浓度的氨氯地平溶液灌胃（1mg·kg^-1·d^-1和10mg·kg^-1·d^-1）。胰岛素抵抗指标采用胰岛素敏感性指数（ISI）=-ln（FBG×FINS）;尾部测量法测血压;放免法测定血清脂联素的浓度。结果：8周后果糖喂养的F、H、L组大鼠血压、空腹胰岛素水平明显升高,ISI、脂联素明显下降,高血压伴胰岛素抵抗大鼠模型成功建立;氨氯地平干预6周后,L、H组较F组空腹胰岛素水平明显下降,ISI、脂联素明显提高;L、H组间对比无明显差异;多元回归分析表明,体质量和胰岛素敏感性是影响脂联素水平的独立因素。结论：氨氯地平可改善高血压伴胰岛素抵抗大鼠的胰岛素敏感性,其机制可能与提高血清脂联素水平有关。     

替米沙坦对原发性高血压患者胰岛素敏感性的影响列腺炎的临床观察

目的:探讨替米沙坦对原发性高血压患者胰岛素敏感性的影响。方法:将60例原发性高血压并糖调节受损患者随机分成观察组和对照组,对照组常规使用卡托普利治疗,观察组使用替米沙坦40～80mg/d,治疗12w后,比较两组血压、空腹(FBG)及餐后血糖(2hBG)、空腹(FINS)及餐后血胰岛素(PINS)、胰岛素敏感指数(ISI)、胰岛素抵抗指数(HOMA-IR)和血脂的变化。结果:治疗12w后,观察组空腹血糖及餐后血糖、空腹及餐后血胰岛素、HOMA-IR显著降低,ISI显著升高,TG显著降低,与对照组比较差异有统计学意义(P<0.001),同时观察组收缩压和舒张压水平显著降低,与治疗前比较差异有统计学意义(P<0.001),但与对照组治疗后比较差异无统计学意义。结论:替米沙坦对原发性高血压患者胰岛素的敏感性具有增强作用,可改善原发性高血压患者胰岛素抵抗及降低甘油三脂,且优于卡托普利。     

青蒿琥酯对小鼠宫颈癌实体瘤和腹水瘤抑制作用的研究

目的观察青蒿琥酯（artesunate,Art）对小鼠宫颈癌实体瘤和腹水瘤生长抑制作用。方法同时建立小鼠宫颈癌U14细胞腹水瘤和实体瘤模型,分别用Art200mg&#183;kg^-1&#183;d^-1、100mg&#183;kg^-1&#183;d^-1、50mg&#183;kg^-1&#183;d^-1、顺铂2mg&#183;kg^-1&#183;d^-1,Art50mg&#183;kg^-1&#183;d^-1顺铂1mg&#183;kg^-1&#183;d^-1治疗腹水瘤和实体瘤小鼠,生理盐水为对照组。观察Art对实体瘤的抑瘤率,对腹水瘤的生命延长率。结果Art对小鼠宫颈癌实体瘤抑瘤率分别为52．59％、44．44％、31．84％、61．45％、51．85％,腹水瘤组生命延长率分别为76．7％、45％、31．7％、100％、93.3％。结论Art能明显抑制小鼠宫颈癌实体瘤和腹水瘤生长,且高剂量组效果明显优于低剂量组。     

替米沙坦与氨氯地平治疗高血压合并糖尿病的疗效观察

目的通过替米沙坦与氨氯地平进行比较,探讨替米沙坦在逆转左室肥厚、改善糖代谢的同时是否能降低血糖水平以及改善胰岛素抵抗。方法2005年2月至2008年5月我院门诊及住院高血压合并2型糖尿病患者108例,随机分为替米沙坦组（n=54）和氨氯地平组（n=54）。替米沙坦组使用替米沙坦口服（80-160 mg·d^-1）,氨氯地平组使用氨氯地平口服（2.5-5 mg·d^-1）,疗程6个月。治疗前后进行血压、超声心动图检查,检测空腹血糖、血清胰岛素、胰岛素抵抗指数,对比分析治疗前、后上述指标的差异。结果与治疗前比较,替米沙坦组和氨氯地平组平均压均有显著下降（P〈0.01）,左心室肥厚,两组均有显著下降,两组间无显著差异（P〉0.05）,替米沙坦组空腹血糖、血清胰岛素、胰岛素抵抗指数有明显下降（P〈0.01）。氨氯地平组在治疗前后空腹血糖、血清胰岛素、胰岛素抵抗指数均无明显变化（P〉0.05）。结论替米沙坦和氨氯地平均能有效控制血压,逆转左心室肥厚,但替米沙坦组空腹血糖、血清胰岛素、胰岛素抵抗指数明显下降,替米沙坦更有利于高血压合并糖尿病的治疗。     

二苯乙烯苷对实验性动脉粥样硬化大鼠血脂和炎症因子的调节作用

目的：探讨二苯乙烯苷（TSG）对大鼠动脉粥样硬化（AS）的预防作用。方法：SD大鼠60只,♂,随机分为6组：正常对照组（普通饲料组）;模型组（高脂饲料）;TSG低剂量组（30mg·kg^-1·d^-1）;TSG中剂量组（60mg·kg^-1·d^-1）;TSG高剂量组（120mg·kg^-1·d^-1）;舒降之对照组（2mg·kg^-1·d^-1）。采用高脂饲料喂饲＋VitD3复制大鼠AS模型。造模12周后,颈动脉取血,检测血清TG、TC、低密度脂蛋白-胆固醇（LDL-C）、高密度脂蛋白-胆固醇（HDL-C）、IL-6、TNF-α及C反应蛋白（CRP）。取血后分离主动脉,置于4%多聚甲醛液,作病理形态学观察。实验数据采用STATA7.0软件进行统计分析。结果：TSG120mg·kg^-1·d^-1和60mg·kg^-1·d^-1能显著降低血浆TG、TC、LDL-C、IL-6、TNF-α、CRP水平及升高HDL-C水平,并呈剂量依赖性。主动脉的苏丹Ⅳ和HE染色病理观察显示,TSG给药组主动脉内皮脂质沉积较模型组少见。结论：TSG对高脂饲料＋VitD3诱导的大鼠AS形成具有预防作用,其机制可能与其调节血脂,抗炎作用有关。     

葛根素联合替米沙坦对肥胖性高血压患者脂肪因子、肾素-血管紧张素系统活性及胰岛素抵抗的影响

目的：观察葛根素联合替米沙坦对肥胖性高血压患者脂肪因子、肾素-血管紧张素系统活性及胰岛素抵抗的影响。方法选取诊治的肥胖性高血压患者160例,随机分为对照组和观察组,每组80例。对照组给予替米沙坦治疗,观察组在对照组基础上加用葛根素治疗,疗程1个月。比较2组体重指数（ BMI）、腰臀比（ W／H）、脂肪因子（脂联素、瘦素、抵抗素）、肾素（PRA）、血管紧张素Ⅱ（AngⅡ）、空腹血糖（FBG）、空腹胰岛素（FLns）、胰岛素抵抗指数（ HOMA-IR）、胰岛素敏感指数（ ISI）变化。结果与对照组比较,观察组治疗后BMI、W／H、瘦素、抵抗素、PRA、AngⅡ、FBG、FLns、HOMA-IR显著降低,脂联素、ISI显著升高,差异均有统计学意义（ P ＜0圹．05）。结论葛根素联合替米沙坦治疗肥胖性高血压能够有效减轻腹型肥胖,调控脂肪因子分泌,抑制肾素-血管紧张素系统的过度激活及改善胰岛素抵抗。     

胰岛素抵抗和脑血管病关系的研究

目的：探讨胰岛素抵抗与脑梗死、脑出血的关系，为针对胰岛素抵抗的治疗可以有效地预防脑血管疾病提供理论依据。方法：选取42例脑梗死（脑梗死组）、40例脑出血（脑出血组）及30例非脑血管病患者（对照组），分别测定空腹胰岛素（FINS）、空腹血糖（FBG），计算胰岛素敏感指数（ISI），各组间进行比较。结果：脑梗死组和脑出血组患者ISI低于对照组（P〈0.05），而FINS高于对照组（P〈0．05），FBG与对照组差异无统计学意义（P〉0．05）。结论：胰岛素抵抗可能是脑血管病的一个重要危险因素。     

国产奥卡西平治疗儿童良性癫痫伴中央颞区棘波的疗效观察

目的：观察国产奥卡西平（OXC）治疗儿童良性癫痫伴中央颞区棘波（BECT）的疗效、安全性和耐受性。方法：用国产OXC单药治疗30例BECT患儿，分析治疗后1，2，3，6个月的疗效和不良反应。OXC起始剂量为5～10mg&#183;kg^-1&#183;d^-1，每隔1周增加1次剂量5～10mg&#183;kg^-1&#183;d^-1,维持剂量20-30mg&#183;kg^-1&#183;d^-1。结果：本组总有效率为86．67％，服药6个月时累积控制率N73．33％，留存率N93．33％。结论：国产OXC治疗BECT的疗效明显，不良反应轻，耐受性好，安全性高。     

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.