瑞舒伐他汀减轻ApoE~(-/-)小鼠动脉硬化形成与ST6Gal-Ⅰ表达相关性研究

目的探讨瑞舒伐他汀抑制ApoE~(-/-)小鼠动脉粥样硬化斑块形成是否与唾液酸转移酶(ST6Gal-Ⅰ)的表达相关。方法取ApoE~(-/-)小鼠,分别采用高脂喂养16周(基线模型组,baseline)、高脂喂养23周(对照组,control)及高脂喂养23周且瑞舒伐他汀灌胃7周(药物组,rosuvastatin)构建模型。分别测定3组ApoE~(-/-)小鼠血清低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、总胆固醇(TC)、甘油三酯(TG)的含量及主动脉斑块面积,分析动脉粥样形成的病理变化,确定高胆固醇血症模型成立。通过免疫组织化学法分析主动脉内膜中ST6Gal-Ⅰ的表达。结果对照组与基线组相比,随着高脂饲料喂养周数增加,小鼠血清中LDL-C、HDL-C、TC、TG均增加,其中LDL-C及TG变化差异具有显著性(P<0.05),其动脉弓斑块面积明显增大(P<0.05),管腔内膜明显增厚(P<0.05),说明高胆固醇血症模型构建成功。而瑞舒伐他汀处理药物组与对照组比较,血脂四项指标、斑块面积均有所下降,且LDL-C、TG水平及斑块面积变化差异均有统计学意义(P<0.05)。分别检测3组ST6Gal-Ⅰ表达显示对照组较基线组动脉弓处表达上调,用药后ST6Gal-Ⅰ表达明显下调。结论瑞舒伐他汀预防小鼠动脉粥样硬化形成的机制可能与ST6Gal-Ⅰ表达密切相关。     

瑞舒伐他汀钙对冠心病患者颈动脉粥样硬化斑块的影响

目的 评价瑞舒伐他汀钙对冠心病患者颈动脉粥样硬化斑块的影响.方法 72例冠心病伴颈动脉粥样硬化的患者口服瑞舒伐他汀钙一日20mg,治疗12月,分别测定其治疗前及治疗3、6、9和12月时总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白-胆固醇(LDL-C)和高密度脂蛋白-胆固醇(HDL-C)水平,以及颈动脉内膜中层厚度(IMT),并计算颈动脉斑块积分.结果 与治疗前比较,治疗3月时TC、TG、LDL-C水平下降(P<0.05),HDL-C水平升高(P<0.05);治疗6、9和12月时TC、TG和LDL-C水平明显下降(P<0.01),HDL-C水平明显升高(P<0.01):治疗9月时IMT缩小且差异有统计学意义(P<0.05),治疗12月时差异非常显著(P<0.01),颈动脉粥样硬化斑块积分和IMT的变化一致.结论 瑞舒伐他汀钙可显著改善冠心病患者的血脂水平,同时可改善其动脉粥样硬化程度.     

瑞舒伐他汀的调脂效果及其对颈动脉粥样斑块的影响

目的观察瑞舒伐他汀对高脂血症患者颈动脉粥样斑块的消退作用及调脂疗效。方法 65例高脂血症患者在常规治疗基础上加服瑞舒伐他汀10 mg/d,测定治疗6个月后总胆固醇(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(LDL-C)及颈动脉斑块的变化。结果治疗后所有患者颈动脉粥样斑块均明显缩小(P<0.01),血脂TC,TG,LDL-C明显下降,HDL-C升高(P<0.01),且无明显不良反应。结论瑞舒伐他汀可缩小颈动脉粥样斑块,有效调节血脂水平,且安全性良好。     

瑞舒伐他汀用于缺血性脑卒中二级预防的疗效及安全性观察

目的:研究瑞舒伐他汀用于缺血性脑卒中二级预防的疗效及安全性。方法:选择我院90例缺血性脑卒中合并高脂血症患者,随机分为瑞舒伐他汀组、辛伐他汀组和饮食控制组,每组30例,瑞舒伐他汀组患者于每晚餐后顿服瑞舒伐他汀钙片10 mg,辛伐他汀组于每晚餐后顿服辛伐他汀片40 mg,饮食控制组采用饮食控制手段,不服用他汀类降脂药物,疗程均为12周。12周后观察3组患者的降脂疗效及安全性。结果:各组患者TC、TG和LDL-C水平均明显降低,但瑞舒伐他汀组的TC、TG、LDL-C水平降低较其他2组明显(P<0.05),3组疗效比较差异有统计学意义(P<0.05)。瑞舒伐他汀钙10 mg组的胆固醇达标率优于辛伐他汀组和饮食控制组,组间差异有统计学意义(χ2=7.937,P<0.05)。结论:瑞舒伐他汀钙用于缺血性脑卒中的二级预防疗效显著,且安全性好,值得临床推广。     

国产瑞舒伐他汀与辛伐他汀治疗高胆固醇血症疗效比较

目的比较国产瑞舒伐他汀5、10mg与辛伐他汀治疗原发性高胆固醇血症疗效。方法对入选患者进行4周筛选,将筛选合格的受试者随机分配为瑞舒伐他汀5mg,瑞舒伐他汀10mg,辛伐他汀20mg,3组均每日服药1次,治疗期共8周,观察调脂疗效和安全性。结果治疗8周末,瑞舒伐他汀5mg,瑞舒伐他汀10mg,辛伐他汀20mg3组TC、LDL-C降低差异有统计学意义（P〈0．01）,TG降低和HDL-C升高差异无统计学意义（P〉0．05）。瑞舒伐他汀5mg,瑞舒伐他汀10mg,辛伐他汀20mg 3组间TC、LDL-C降低差异均无统计学意我（P〈0．05）,TG降低、HDL-C升高差异均无统计学意义（P〉0．05）。安全性：3组不良反应发生率差异均有统计学意义（P〉0．05）。结论瑞舒伐他汀5mg组、瑞舒伐他汀10mg组均能明显降低TC、TG、LDL-C,升高HDL—C,调脂疗效确切。瑞舒伐他汀安全性好。瑞舒伐他汀5mg、10mg可用于治疗原发性高胆固醇血症患者。     

瑞舒伐他汀钙对高龄冠心病患者颈动脉粥样硬化斑块的影响

目的探讨瑞舒伐他汀钙对高龄患有冠状动脉粥样硬化性心脏病患者合并颈动脉粥样硬化斑块的作用。方法 58例高龄冠状动脉粥样硬化性心脏病合并颈动脉粥样硬化的患者给予口服瑞舒伐他汀钙10mg/次,1次/d,治疗1年,分别监测治疗前和治疗3、6、9个月及1年时总胆固醇(TC)含量、三酰甘油(TG)浓度、低密度脂蛋白-胆固醇(LDL-C)含量以及高密度脂蛋白-胆固醇(HDL-C)含量的水平和颈动脉内膜中层厚度(IMT),并推算颈动粥样硬化斑块的积分值。结果与治疗前比较,治疗3个月时血清中TC、TG、LDL-C的浓度水平降低(P<0.05),血清中HDL-C的浓度水平增高(P<0.05);治疗6、9个月及1年时,TC、TG及LDL-C水平显著降低(P<0.01),HDL-C水平显著增加(P<0.01);颈动脉粥样硬化斑块积分与IMT药物治疗1年时差异有统计学意义(P<0.05)。结论瑞舒伐他汀钙能明显改善冠心病患者血清中血脂的浓度,还能稳定及逐渐减少动脉粥样硬化斑块。     

瑞舒伐他汀对冠心病患者的调脂作用以及安全性分析

目的：探讨瑞舒伐他汀对冠心病患者的调脂作用以及安全性。方法110例冠心病合并高脂血症患者,随机分为观察组(57例)与对照组(53例),观察组患者接受瑞舒伐他汀治疗,对照组患者接受阿托伐他汀治疗,连续治疗8周后进行疗效与安全性评价。结果治疗前,两组患者甘油三酯(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(HDL-C)、载脂蛋白AI(ApoAI)、载脂蛋白B(ApoB)相比差异无统计学意义(P>0.05);治疗后,观察组TG、TC、LDL-C、ApoB显著低于对照组, HDL-C、ApoAI显著高于对照组,差异有统计学意义(P<0.05)。两组患者不良反应发生率相比差异无统计学意义(P>0.05)。结论瑞舒伐他汀对冠心病患者的调脂作用良好,且不良反应发生率低,值得临床推广应用。     

瑞舒伐他汀与普罗布考抗大鼠动脉粥样硬化机制研究

目的 探讨选择性HMG-COA还原酶抑制剂瑞舒伐他汀(Rosuvastatin)与抗氧化剂普罗布考(Probucol)对大鼠动脉粥样硬化形成的影响,并研究其机制。方法 60只Wistar雄性大鼠,随机分5组,正常饮食组(A组),高脂饮食组(B组),瑞舒伐他汀组(C组),普罗布考组(D组),瑞舒伐他汀联合普罗布考组(E组),每组12只。以高脂饲料喂养加腹腔注射VD₃建立大鼠动脉粥样硬化(AS)模型。第9周,C、D、E组大鼠在高脂喂养基础上给予药物干预。16周末处死各组大鼠,采血检测血脂,酶联免疫吸附法检测血浆氧化低密度脂蛋白(OX-LDL),血清丙二醛(MDA)、超氧化物歧化酶(SOD)、血管内皮细胞钙黏蛋白(VE-cadherin);免疫组织化学法检测主动脉血小板内皮细胞黏附分子1(PECAM-1)的表达;光镜下观察主动脉血管壁病理组织学改变。结果 与A组比较,B、C、D、E组大鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)显著增高(P<0.01),高密度脂蛋白(HDL)降低(P<0.01),OX-LDL、VE-cadherin、MDA升高(P<0.01),而SOD降低(P<0.01),光镜下观察主动脉内膜厚度增加,内膜损害严重,动脉血管PECAM-1表达升高(P<0.01)。与B组比较,C、D、E组大鼠血清TC、LDL-C含量降低(P<0.01),OX-LDL、VE-cadherin、MDA明显下降(P<0.01),SOD升高(P<0.05),光镜下血管内膜较B组薄,内膜损害减轻,PECAM-1表达降低(P<0.01)。与C组比较,D组和E组OX-LDL、MDA降低(P<0.05),SOD升高(P<0.05)。结论 普罗布考降低TC、LDL-C作用,以及抗炎效用与瑞舒伐他汀疗效相似,普罗布考有显著的抗氧化作用,抗氧化疗效优于瑞舒伐他汀,两药合用可减缓AS进展。     

瑞舒伐他汀联合阿司匹林治疗颈动脉粥样硬化的临床观察

目的:观察瑞舒伐他汀联合阿司匹林治疗颈动脉粥样硬化的临床疗效和安全性。方法:150例颈动脉粥样硬化患者随机均分为A组、B组和C组。3组患者均给予低脂饮食等常规治疗。在此基础上,A组患者给予阿司匹林肠溶片100 mg,口服,每日1次;B组患者给予瑞舒伐他汀钙片10 mg,口服,每日1次;C组患者给予阿司匹林肠溶片(用法用量同A组)+瑞舒伐他汀钙片(用法用量同B组)。3组患者疗程均为6个月。观察3组患者临床疗效,治疗前后的血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、发生心脏缺血事件例数、劲动脉内中膜厚度(IMT)及不良反应发生情况。结果:C组患者总有效率显著高于A组及B组,3组比较差异有统计学意义(P<0.05)。治疗前3组患者TC、TG、LDL-C、HDL-C、发生心脏缺血事件例数、IMT比较,差异均无统计学意义(P>0.05);治疗后3组患者TC、TG、LDL-C、发生心脏缺血事件例数、IMT均显著低于同组治疗前,且C组低于A组及B组,差异均有统计学意义(P<0.05)。3组患者治疗期间均未见明显不良反应发生。结论:瑞舒伐他汀联合阿司匹林治疗颈动脉粥样硬化较单用瑞舒伐他汀或阿司匹林疗效更显著,安全性相似。     

瑞舒伐他汀钙对脑梗死患者血脂、超敏C-反应蛋白、动脉粥样硬化的影响

目的观察瑞舒伐他汀钙对脑梗死患者的血脂、超敏C-反应蛋白(hs-CRP)、动脉粥样硬化的影响。方法对68例脑梗死患者应用瑞舒伐他汀钙10mg/d口服,1周后观察hs-CRP的变化,治疗6个月后,观察用药前后血脂及颈动脉内膜中层厚度(IMT)的变化。结果经治疗1周后脑梗死患者的hs-CRP下降,6个月后患者血脂中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)均有下降,高密度脂蛋白胆固醇(HDL-C)升高,IMT下降,且均有统计学差异(P<0.05或P<0.01)。结论瑞舒伐他汀钙可降低脑梗死患者的hs-CRP、LDL-C、TC、TG,升高HDL-C,并具有抗动脉粥样硬化的作用。     

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.