盐酸西布曲明对高脂肥胖大鼠下丘脑增食欲素系统的影响

目的观察盐酸西布曲明对高脂饮食肥胖大鼠下丘脑增食欲素系统基因表达的变化。方法建立高脂饮食肥胖大鼠模型,分组连续灌胃给药4wk,观察盐酸西布曲明给药对高脂饮食肥胖大鼠体重、血脂、血糖及下丘脑前增食欲素原及增食欲素受体mRNA表达的影响。结果盐酸西布曲明8mg·kg-1能明显降低高脂肥胖大鼠体重、血糖和血脂;升高肥胖大鼠下丘脑前增食欲素原mRNA表达水平;各组间增食欲素受体1和2mRNA表达无变化。结论盐酸西布曲明具有减重、降脂和增加高脂饮食肥胖大鼠下丘脑前增食欲素原基因表达的作用。     

糖尿病性肥胖大鼠模型的建立及西布曲明对其治疗作用的研究

目的:研究链脲佐菌素(STZ)联合高营养饲料诱导的大鼠糖尿病性肥胖模型的特点,以及盐酸西布曲明对此种模型的治疗作用。方法:先用小剂量STZ(25mg/kg)尾静脉注射诱导大鼠产生糖尿病,再用高营养饲料喂养4个月建立糖尿病性肥胖模型。盐酸西布曲明4mg/kg灌胃治疗17d,给药期间定时测定体重及摄食量,15d时测定糖耐量,实验终点时测定体重、内脏脂肪及右比目鱼肌重量;取血分离血清测定血脂、血糖和血清胰岛素水平,并计算胰岛素抵抗指数。结果:模型组大鼠体重、内脏脂肪重量及系数均显著升高,而右比目鱼肌系数显著降低;空腹血糖、血胰岛素水平显著升高,并出现糖耐量异常及胰岛素抵抗;TG水平显著升高,而高密度脂蛋白胆固醇(HDL-C)水平显著降低。盐酸西布曲明可减轻糖尿病肥胖大鼠的体重、内脏脂肪含量和系数,改善高胰岛素血症和胰岛素抵抗,降低血TG水平,同时升高HDL-C水平。对右比目鱼肌系数,血糖、总胆固醇和低密度脂蛋白胆固醇(LDL-C)水平,以及糖耐量无明显影响。结论:STZ联合高营养饲料可成功诱导糖尿病性肥胖的大鼠模型,盐酸西布曲明对大鼠糖尿病肥胖具有一定的治疗作用。     

西布曲明片治疗单纯性肥胖的临床研究

目的 :评价西布曲明 (sibutramine)对单纯性肥胖或体重指数 (BMI)≥ 2 5的超重者的减肥疗效及安全性。方法 :以安慰剂作为对照进行 8wk的随机双盲、多中心临床研究 ;试验组、对照组各纳入受试者 10 4例 ,每日 1次饭前或饭后 1h口服西布曲明片 10mg或相同片数的安慰剂。 8wk启盲后 ,试验组继续用药观察至 2 4wk。结果 :西布曲明可明显减少受试者的腰围、臀围、BMI、体重 (P <0 .0 1) ,总有效率为 73.8% ,对照组为 15 .5 % ,P <0 .0 1。对血脂及血糖的影响 2组间差异无显著意义。治疗至 8wk末西布曲明不良反应发生率为5 8.6% ,对照组为 4 1.4 %。 2 4wk末西布曲明不良反应发生率为 35 .7%。未发现严重的不良反应。结论 :西布曲明片是疗效肯定、不良反应较轻、给药方便、依从性高的减肥药     

茶多酚对奥氮平诱导肥胖大鼠的减肥作用及其机制

目的探讨茶多酚对奥氮平诱导肥胖大鼠的减肥作用及其机制。方法 SD雌性大鼠50只,随机分为正常对照组(10只)和奥氮平诱导肥胖模型组(40只)。肥胖模型组于黑暗时相前1h奥氮平1.2 mg·kg~(-1)·d~(-1)灌胃,正常对照组给予等容量蒸馏水,连续2 wk。于wk 3开始,再将肥胖模型大鼠随机分为4组:模型组、西布曲明(2.5 mg·kg~(-1)·d~(-1))组、茶多酚低(150 mg·kg~(-1)·d~(-1))剂量组和茶多酚高(300 mg·kg~(-1)·d~(-1))剂量组,每组10只。连续给药5 wk。观察大鼠体重、肾和子宫周围脂肪湿重,计算Lee's指数和脂肪系数,测定血清瘦素、脂联素水平以及超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果与正常对照组相比,模型组大鼠体重和脂肪湿重及Lee's指数和脂肪系数均增加,血清瘦素水平升高,脂联素水平降低(P<0.05)。与模型组比较,茶多酚低、高剂量组大鼠体重和脂肪湿重降低,Lee's指数、脂肪系数降低,SOD活性增加,MDA含量减少(P<0.05)。与模型组比较,茶多酚高剂量组血清脂联素水平升高(P<0.05),瘦素水平无显著差异(P>0.05)。结论茶多酚对奥氮平诱导的肥胖大鼠有减肥作用,其作用机制可能与增强脂联素的调节和提高抗氧化能力有关。     

D-异苯环戊胺对营养性肥胖模型大鼠的减肥作用研究

目的:探讨D-异苯环戊胺的减肥作用。方法:建立营养型肥胖大鼠模型,选取造模成功的50只♂大鼠分为5组,即模型组、西布曲明组及D-异苯环戊胺大、中、小剂量组,另设正常对照组(10只),共6组。各实验组分别连续灌胃给予相应药物4周,于末次给药并禁食12 h后,测量体长、尾长计算Lee’s指数,并观测各组大鼠体质量、肾周脂肪重量、脂肪系数、睾周脂肪细胞数量、脂肪细胞大小以及血脂、血糖水平的变化情况。结果:与模型组比较,D-异苯环戊胺各剂量组大鼠体质量、Lee’s指数、肾周脂肪质量、脂肪系数及睾丸周围脂肪细胞大小、血糖、血脂水平均明显降低(P<0.05或P<0.01),并存在一定的量效关系;其中D-异苯环戊胺大剂量组与西布曲明组各指标比较无显著性差异(P>0.05),中、小剂量对大鼠体脂和脂肪细胞的影响不及西布曲明(P<0.05或P<0.01)。结论:D-异苯环戊胺有较明显的减肥作用。     

β-壳寡糖对营养性肥胖大鼠的减肥作用研究

目的:通过建立营养性肥胖大鼠模型研究β-壳寡糖对营养性肥胖大鼠的减肥作用。方法:通过高脂饮食诱导建立肥胖模型,灌胃给予治疗一个月,观察治疗前后体重、肥胖指数的变化,检测血清生化指标及脂肪,肝脏病理情况。结果:13周末成功建立营养性肥胖模型,灌胃一月后,体重上β-壳寡糖各剂量组与模型组存在显著性差异(P<0.05),其中高剂量组差异非常显著(P<0.01);各用药组均有降低血清总胆固醇(CHO)的作用(P<0.05),其中低、中剂量组及阳性药组差异非常显著(P<0.01),β-壳寡糖低、中剂量组低密度脂蛋白胆固醇(LDLC)与模型组相比差异存在统计学意义(P<0.05),血甘油三酯(TG)及高密度脂蛋白胆固醇(HDLC)各组间则无显著差异(P>0.05),生殖器周及肾周脂肪量,Lee's指数各组明显低于模型组(P<0.05)。结论:β-壳寡糖各组均有减肥作用,从降低体重上看,高剂量组要优于低、中剂量组;从CHO及LDLC上看,低、中剂量组要优于高剂量组。     

加味苓桂术甘汤对奥氮平诱导肥胖大鼠的减肥作用

目的:探讨加味苓桂术甘汤(LGSG)对抗精神病药奥氮平(olanzapine)诱导肥胖大鼠的减肥作用。方法:SD雌性大鼠70只,按体质量随机分为正常对照组10只,其余60只灌胃给予奥氮平(1.2mg.kg-1.d-1)2周。将造模成功的40只肥胖大鼠随机分为模型组、盐酸西布曲明组(2.5mg.kg-1.d-1)、加味苓桂术甘汤低(4.5g.kg-1.d-1)、高(9.0g.kg-1.d-1)剂量组,每组10只。动物继续给予奥氮平处理,同时灌胃给予上述药物处理5周,并于药物处理结束时测定大鼠体质量、Lee’s指数、肾和子宫周围脂肪垫湿重、脂肪系数、血脂的变化。结果:加味苓桂术甘汤处理肥胖大鼠5周后,饮食量和体质量明显低于模型组大鼠,脂肪湿重和脂肪系数明显减少(P<0.05或P<0.01),血清游离脂肪酸(FFA)明显减少(P<0.05或P<0.01),高密度脂蛋白胆固醇(HDL-C)明显增加(P<0.05或P<0.01),其中加味苓桂术甘汤高剂量还能明显降低肥胖大鼠的Lee’s指数(P<0.05)。结论:加味苓桂术甘汤对奥氮平诱导的肥胖大鼠具有降低体质量,抑制肥胖,调节血脂的作用,其作用可能与减少动物摄食,增加...     

西布曲明对不同肥胖者的减重作用

目的 :观察盐酸西布曲明在不同体重病人中的减重作用。方法 :40名肥胖患者 ,根据体重指数(BMI)分组 :肥胖早期组 (n =1 0 )、Ⅰ度肥胖组 (n =1 1 )、Ⅱ度肥胖组(n =1 9) ,40名患者都给予饮食、体育活动和生活方式的改变标准化 ,在此基础上给予盐酸西布曲明 1 0mg·d-1,治疗期 1 2wk。结果 :3组病人体重均有不同程度的下降 ,服药 2wk后Ⅰ度肥胖组有效 5例 (4 5 .5 % ) ,Ⅱ度肥胖组有效 1 8例(94.7% ) (P <0 .0 1 ) ;服药 4wk ,Ⅰ度肥胖组有效 9例(81 .8% ) ,显效 1例 (9.1 % ) ,Ⅱ度肥胖组有效 3例(5 .8% ) ,显效 1 6例 (84.2 % ) (P <0 .0 1 ) ;服药1 2wk,肥胖早期组始出现 5例有效 (5 5 .6% ) ,Ⅰ度肥胖组有效 4例 (3 6.4% ) ,显效 7例 (63 .6% ) ,Ⅱ度肥胖组显效 1 9例 (1 0 0 % ) (P <0 .0 1 )。结论 :盐酸西布曲明是一安全有效的减肥药 ,并随体重的不同疗效不一 ,疗效与基础体重成正比。     

盐酸特拉唑嗪的药效学观察

目的　 观察国产盐酸特拉唑嗪的降压作用。 方法 　观察单次和连续多次灌胃盐酸特拉唑嗪对自发性高血压大鼠和肾型高血压大鼠的降压作用。 结果 　盐酸特拉唑嗪单次灌胃给药剂量依赖性 ,降低自发性高血压大鼠的收缩压 ;连续 2周灌胃给药剂量依赖性降低自发性高血压大鼠和肾型高血压大鼠的收缩压。 结论 　盐酸特拉唑嗪具有明显的降压作用     

化湿减肥方对幼年营养性肥胖大鼠血糖代谢的影响

目的探讨化湿减肥方对幼年营养性肥胖大鼠体质量、血脂、血糖的影响。方法将60只Wistar雄性大鼠随机分为正常组(15只)和造模组(45只),分别予以基础饲料和高脂饲料喂养,造模7周后,造模组大鼠随机分为模型组、对照组、化湿减肥组,每组15只。正常组和模型组给予蒸馏水,对照组给予L-肉碱,化湿减肥组给予化湿减肥方,每天灌胃1次,连续灌胃8周后,对各组大鼠的体质量、Lee’s指数进行统计分析,并对血清中总胆固醇(TC)、甘油三酯(TG)、血糖(Glu)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)水平进行比较。结果与正常组比较,模型组大鼠体质量和Lee’s指数,TC,TG,Glu,LDL均有所升高,HDL水平明显降低(P0.05或P0.01);与模型组比较,对照组和化湿减肥组上述各指标均有不同程度的改善(P0.05或P0.01),且化湿减肥组改善程度更为显著(P0.01)。结论化湿减肥方对幼年营养性肥胖大鼠有明显的减肥及改善糖脂代谢的作用。     

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.     

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.     

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.