槲皮素对胃癌相关p53/AMPK/mTOR信号通路的影响

目的　探讨槲皮素（QE）对胃癌相关p53/AMPK/mTOR信号通路的影响。方法　将胃癌细胞分为QE组和溶剂组,QE组以DMSO为溶剂按配制QE浓度分别为0.02、0.04、0.06及0.08 mmol/L,对细胞进行干预,分别为QEA、QEB、QEC、QED组,溶剂组加入等量不含QE的溶剂。MTT实验检测槲皮素对胃癌细胞增殖的影响;MDC染色法检测槲皮素对胃癌细胞自噬的影响;双染法检测槲皮素对胃癌细胞凋亡的影响;实时荧光定量聚合酶链反应检测细胞内p53、AMPK及mTOR的mRNA相对表达水平;Western blot检测细胞内LC3Ⅱ/LC3Ⅰ、P53、AMPK、mTOR蛋白表达差异。结果　与溶剂组相比,QE各剂量组胃癌细胞的自噬程度和凋亡率均显著增加,细胞中LC3Ⅱ/Ⅰ蛋白表达量上调,p53、AMPK mRNA和蛋白水平均上调,mTOR的mRNA和蛋白表达量均下调（P＜0.05）,且呈剂量依赖性。结论　QE可以抑制胃癌细胞增殖,诱导其发生自噬、促进其凋亡,其作用机制可能与p53/AMPK/mTOR信号通路有关。     

基于LKB1/AMPK信号通路探究金雀异黄酮对癫痫大鼠海马神经元凋亡和自噬的影响

摘要：目的:基于肝激酶B1（LKB1）/5’-磷酸腺苷激活的蛋白激酶（AMPK）信号通路探究金雀异黄酮对癫痫大鼠海马神经元凋亡和自噬的影响。方法:于腹腔内注射氯化锂与匹罗卡品诱导建立癫痫大鼠模型,随机分为5组（每组12只）:模型组、金雀异黄酮低剂量组(7 mg·kg-1)、金雀异黄酮高剂量组(14 mg·kg-1)、金雀异黄酮(14 mg·kg-1)+空载（空载质粒）组、金雀异黄酮(14 mg·kg-1)+LKB1敲低（LKB1 siRNA质粒）组,另取12只Wistar大鼠,腹腔内注射等剂量生理盐水作为正常对照组,以金雀异黄酮和质粒分组给药干预后,检测各组大鼠癫痫评分及平均癫痫发作时间;以跳台实验检测各组大鼠学习记忆能力;以原位末端标记法（TUNEL）染色检测各组大鼠海马神经元凋亡率;以酶联免疫吸附测定（ELISA）试剂盒测量各组大鼠血清致炎因子环氧化酶-2（COX-2）、白细胞介素（IL）-1β、IL-17水平;以免疫印迹检测各组大鼠脑组织自噬、凋亡及LKB1/AMPK通路蛋白表达。结果:与正常对照组相比,模型组大鼠癫痫评分、平均癫痫发作时间、跳台实验犯错次数、海马神经元凋亡率、血清COX-2、IL-1β及IL-17水平、脑组织凋亡蛋白半胱氨酸蛋白酶-3（caspase-3）、B淋巴细胞瘤-2基因（Bcl-2）相关X蛋白（Bax）表达水平显著升高（P＜0.05）,大鼠跳台实验潜伏期、脑组织自噬蛋白LC3-II/LC3-I、P62及LKB1/AMPK通路蛋白p-AMPK/AMPK、LKB1表达水平显著降低（P＜0.05）;与模型组相比,金雀异黄酮低、高剂量组大鼠癫痫评分、平均癫痫发作时间、跳台实验犯错次数、海马神经元凋亡率、血清COX-2、IL-1β及IL-17水平、脑组织凋亡蛋白caspase-3、Bax表达水平显著降低（P＜0.05）,大鼠跳台实验潜伏期、脑组织自噬蛋白LC3-II/LC3-I、P62及LKB1/AMPK通路蛋白p-AMPK/AMPK、LKB1表达水平显著升高（P＜0.05）,且金雀异黄酮低、高剂量组间各指标差异均有统计学意义（P＜0.05）;与金雀异黄酮高剂量组相比,金雀异黄酮+LKB1敲低组大鼠癫痫评分、平均癫痫发作时间、跳台实验犯错次数、海马神经元凋亡率、血清COX-2、IL-1β及IL-17水平、脑组织凋亡蛋白caspase-3、Bax表达水平显著升高（P＜0.05）,大鼠跳台实验潜伏期、脑组织自噬蛋白LC3-II/LC3-I、P62及LKB1/AMPK通路蛋白p-AMPK/AMPK、LKB1表达水平显著降低（P＜0.05）。结论:金雀异黄酮可通过激活LKB1/AMPK信号而减轻癫痫大鼠炎症,增强脑组织自噬,抑制大鼠海马神经元凋亡,提高其学习记忆能力,改善其癫痫症状。     

芦荟大黄素对胃癌SGC-7901细胞凋亡、自噬及p53/AMPK/mTOR信号通路的影响

摘 要 目的：探讨芦荟大黄素（AE）对胃癌SGC-7901细胞凋亡、自噬及p53蛋白（p53）/磷酸腺苷蛋白激酶（AMPK）/雷帕霉素靶蛋白（mTOR）信号通路的影响。 方法: 实验分为对照组（AE 0 μmol·L-1）、AE低（10 μmol·L-1）、中（30 μmol·L-1）、高（50 μmol·L-1）剂量组和自噬阻断剂3 甲基腺嘌呤（3 MA）+ AE组（20 μmol·L-1+50 μmol·L-1）。CCK 8法检测各组细胞增殖抑制率,采用透射电镜及单丹磺酰尸胺（MDC）染色观察各组细胞自噬体及自噬溶酶体的变化,采用末端脱氧核苷酸转移酶介导的dUTP 缺口末端标记测定（TUNEL）法观察各组细胞凋亡率变化,Western blot法检测各组细胞p53、AMPK、mTOR信号通路蛋白及自噬标致蛋白Beclin 1蛋白（Beclin 1）、微管相关轻链蛋白Ⅰ（LC3Ⅰ）及微管相关轻链蛋白Ⅱ（LC3Ⅱ）表达情况。 结果: 与对照组相比,AE各剂量组及3 MA+AE组细胞的增殖抑制率、凋亡指数（AI）显著升高（P<0.05）,且呈剂量依赖性;AE中、高剂量组的增殖抑制率和AI与3 MA+AE组相比差异有统计学意义（P<0.05）。与对照组相比,AE各剂量组细胞自噬体、自噬空泡增多,溶酶体积分光密度（IOD）/所选区域面积（Area）值及p53、AMPK、Beclin 1表达显著升高,mTOR表达及LC3Ⅰ/LC3Ⅱ比值显著降低（P<0.05）,且呈剂量依赖性;3 MA+AE组细胞自噬体、自噬空包等超微结构减少,IOD/Area值及p53、AMPK及Beclin 1表达显著降低,mTOR表达及LC3Ⅰ/LC3Ⅱ比值显著升高（P<0.05）。 结论: AE可通过提高胃癌SGC-7901细胞自噬水平,诱导SGC-7901细胞凋亡,其机制可能与促进p53/AMPK/mTOR信号通路表达有关。     

柚皮素通过AMPK通路介导的自噬对顺铂耐药宫颈癌细胞(HeLa/DDP)顺铂耐药性的影响

目的探究柚皮素对顺铂耐药宫颈癌细胞(HeLa/DDP)顺铂耐药性的影响,并探究其分子机制。方法体外培养人HeLa/DDP细胞、HeLa细胞,CCK-8法检测不同质量浓度顺铂对HeLa/DDP、He La细胞增殖的影响及不同质量浓度柚皮素对HeLa/DDP细胞增殖的影响。设置对照组、顺铂组(2 mg/L顺铂)、顺铂+柚皮素组(2 mg/L顺铂+60 mg/L柚皮素)和顺铂+柚皮素+AMPK通路抑制剂组(2mg/L顺铂+60mg/L柚皮素+50μmol/LCompoundC);CCK-8法检测各组HeLa/DDP细胞增殖情况;流式细胞仪检测各组HeLa/DDP细胞凋亡情况;蛋白免疫印迹(Westernblotting)法检测各组HeLa/DDP细胞中腺苷酸活化蛋白激酶(AMPK)、p-AMPK、Bcl-2相关X蛋白(Bax)、Beclin1、微管相关蛋白1轻链3(LC3)Ⅰ、LC3Ⅱ蛋白表达情况。结果顺铂对HeLa/DDP细胞、HeLa细胞的半数抑制浓度(IC50)分别在4～8、1～2 mg/L,柚皮素对HeLa/DDP细胞的IC50在30～60mg/L。与对照组相比,顺铂组He La/DDP细胞增殖抑制率、凋亡率及细胞中p-AMPK/AMPK、Bax、Beclin1、LC3Ⅱ蛋白表达水平显著升高(P0.05),LC3Ⅰ蛋白表达水平显著降低(P0.05);与顺铂组相比,顺铂+柚皮素组HeLa/DDP细胞增殖抑制率、凋亡率及细胞中p-AMPK/AMPK、Bax、Beclin1、LC3Ⅱ蛋白表达水平显著升高(P0.05),LC3Ⅰ蛋白表达水平显著降低(P0.05);与柚皮素组相比,AMPK通路抑制剂组He La/DDP细胞增殖抑制率、凋亡率及细胞中p-AMPK/AMPK、Bax、Beclin1、LC3Ⅱ蛋白表达水平显著降低(P0.05),LC3Ⅰ蛋白表达水平显著升高(P0.05)。结论柚皮素可能通过激活AMPK通路介导的自噬反应,与顺铂联用发挥对HeLa/DDP细胞增殖抑制作用及凋亡促进作用。     

当归芍药散通过AMPK/mTOR通路对高糖诱导的足细胞损伤的影响

目的:探讨当归芍药散是否可以通过AMPK/mTOR信号通路激活自噬改善高糖诱导的足细胞损伤。方法:分别将足细胞分为正常对照组、模型组、当归芍药散含药血清组、自噬抑制剂组、当归芍药散含药血清加自噬抑制剂组、自噬激动剂、AMPK抑制剂、当归芍药散含药血清加AMPK抑制剂组和AMPK激动剂，并观察各组的自噬相关蛋白、细胞活性和细胞凋亡率。结果:与对照组相比，高糖组足细胞活力和Beclin-1/LC3/p-AMPK蛋白表达均降低，细胞凋亡率和p-mTOR蛋白表达均增加(P<0.01);和高糖组相比，当归芍药散含药血清组、自噬激动组、AMPK激动剂组的细胞活力和Beclin-1/LC3Ⅱ/p-AMPK蛋白表达均提高，细胞凋亡率和p-mTOR蛋白表达均降低(P<0.01);与高糖组相比，自噬抑制剂组、AMPK抑制剂组足细胞的细胞活力和Beclin-1/LC3Ⅱ/p-AMPK蛋白表达均降低，细胞凋亡率和p-mTOR蛋白表达均增加(P<0.01)。结论:当归芍药散可以通过AMPK/mTOR通路激活自噬改善高糖诱导的足细胞损伤。     

金匮肾气汤促进糖尿病小鼠肾脏足细胞自噬

目的探讨金匮肾气汤对db/db糖尿病小鼠肾脏足细胞自噬的影响及机制。方法将6周龄db/db糖尿病小鼠随机分为生理盐水组、金匮肾气汤低、高剂量组、二甲双胍组,均灌胃给药;♂db/m小鼠作为正常对照组。于第18周龄处死动物,留24 h尿检测尿白蛋白、肌酐;取血,检测血糖、肌酐;留取肾脏组织,分别进行PAS染色观察肾小球内细胞外基质增生情况,免疫组织化学检测WT1在肾组织的表达,透射电子显微镜观察足细胞内自噬体情况,Western blot检测LC3Ⅰ/Ⅱ、p62、p-mTOR/mTOR、p-AMPK/AMPK在肾组织的表达。结果与db/db糖尿病小鼠组比较,金匮肾气汤治疗后,24 h尿白蛋白减少、尿白蛋/肌酐下降、血肌酐下降(P<0.05),肾小球内系膜增宽程度减轻,足细胞内自噬体增加,WT1阳性细胞核数量明显增加(P<0.05),肾皮质内LC3Ⅱ表达明显增强、p62表达明显降低(P<0.05),AMPK磷酸化明显增加,mTOR磷酸化受到抑制(P<0.05)。结论金匮肾气汤通过AMPK-mTOR途径,促进足细胞自噬,保护足细胞,延缓糖尿病肾病的进展。     

通冠胶囊后适应对大鼠心肌缺血再灌注损伤的保护作用及机制的研究

目的 通过制备大鼠心肌缺血再灌注模型,并在此基础上研究通冠胶囊不同剂量后适应以及缺血后适应方法对大鼠心肌梗死程度、心肌细胞凋亡状况的影响及作用机制.方法 采用结扎心脏左前降支的方法制备大鼠心肌缺血再灌注模型,并随机分为6组.实验结束后每组半数行NBT染色法及称重法测定心肌梗死范围;半数进行免疫组化法测定BCL-2蛋白及BAX蛋白表达;并行TUNEL染色测定凋亡指数;心尖部心肌组织测MDA及SOD水平.结果 与SO组相比较,各组的梗死范围均明显增加(P<0.01),表明心肌缺血再灌注模型成功.与I/R组相比较,IPC组与通冠胶囊HD组均可明显降低心肌梗死范围(P<0.01);SO组仅个别细胞凋亡;I/R组凋亡的心肌细胞明显增加,通冠胶囊LD组凋亡的心肌细胞数量也较多,呈弥漫分布;IPC组、通冠胶囊MD组、HD组凋亡的心肌细胞数减少,IPC组、通冠胶囊MD组、HD组凋亡细胞呈散在分布;与IR组相比,IPC组、通冠胶囊MD组、HD组凋亡细胞教减少,差异有统计学意义(P<0.05),IPO1组与IPO2两组相比差异有统计学意义(P<0.05).与SO组相比较,其余各组反应心肌氧化损伤的心肌组织脂质过氧化产物MDA含量增加,SOD活性降低,差异有统计学意义(P<0.01);与IR组相比,IPC组、MD组、HD组心肌MDA含量下降、SOD活性升高,差异有统计学意义(P<0.05);与SO组相比较,其余各组BCL-2及BAX蛋白表达均明显上升,差异有统计学意义(P<0.01).IPC组、MD组及HD组BCL-2蛋白表达均高于IR组(P<0.01);IPc组BAX蛋白表达低于IR组(P<0.01).结论 通冠胶囊后适应的心肌保护作用可通过降低局部氧自由基生成,升高BCL-2蛋白表达,提高BCL-2/BAX比值,抑制心肌细胞凋亡实现.通冠胶囊后适应可部分起到模拟缺血后适应的作用,且作用程度与剂量具有相关性.     

PI3Kγ抑制剂AS605240与5-氟尿嘧啶联合应用对小鼠乳腺癌细胞增殖及转移的影响

目的探讨PI3Kγ抑制剂AS605240与化疗药物联合应用对小鼠乳腺癌细胞增殖及转移的影响。方法将小鼠乳腺癌细胞株4T1分为4组,对照组:取10 m L人肝癌HCCLM3细胞液(细胞浓度为5×106/m L)于10%胎牛血清的DMEM培养液中,置于CO_2培养箱(37℃、5%CO_2、20%O_2);5-氟尿嘧啶组、PI3Kγ抑制剂组、联合组的培养方法同对照组,其10%胎牛血清DMEM培养液分别含有10μg/m L 5-氟尿嘧啶、10μmol/m L PI3Kγ抑制剂AS605240及10μg/m L 5-氟尿嘧啶+10μmol/m L PI3Kγ抑制剂AS605240。以上各组每孔设6个平行样,培养72 h后,MTT法检测小鼠乳腺癌细胞株4T1活力,酶联免疫吸附法测定Ki-67、cyc D1、β-catenin、VEGF、p53、CD31蛋白水平。结果 5-氟尿嘧啶组、PI3Kγ抑制剂组、联合组的OD值、存活率(%)均低于对照组,差异有统计学意义(P<0.05);联合组OD值、存活率(%)低于5-氟尿嘧啶组、PI3Kγ抑制剂组,差异有统计学意义(P<0.05);5-氟尿嘧啶组OD值、存活率与PI3Kγ抑制剂组比较差异无统计学意义(P>0.05)。5-氟尿嘧啶组、PI3Kγ抑制剂组、联合组的Ki-67、cyc D1、β-catenin蛋白水平均低于对照组,差异有统计学意义(P<0.05);联合组Ki-67、cyc D1、β-catenin蛋白水平低于5-氟尿嘧啶组、PI3Kγ抑制剂组,差异有统计学意义(P<0.05);5-氟尿嘧啶组Ki-67、cyc D1、β-catenin与PI3Kγ抑制剂组比较差异无统计学意义(P>0.05)。5-氟尿嘧啶组、PI3Kγ抑制剂组、联合组的VEGF蛋白水平低于对照组,p53蛋白水平高于对照组,差异有统计学意义(P<0.05);联合组VEGF蛋白水平低于5-氟尿嘧啶组、PI3Kγ抑制剂组,p53蛋白水平高于5-氟尿嘧啶组、PI3Kγ抑制剂组,差异有统计学意义(P<0.05);5-氟尿嘧啶组的VEGF、p53与PI3Kγ抑制剂组比较差异无统计学意义(P>0.05)。结论 PI3Kγ抑制剂AS605240与5-氟尿嘧啶联合作用能明显抑制小鼠乳腺癌细胞增殖和转移,其机制可能与细胞周期、p53蛋白的调控以及Wnt-β-catenin信号通路、VEGF的抑制有关。     

p53和Ki67蛋白在胃癌中的表达及临床意义

目的：探讨p53和Ki67蛋白在胃癌中的表达及临床意义。方法选取2010年12月—2013年12月彭州市中医医院收治的胃癌患者68例作为胃癌组;另选取同期彭州市中医医院收治的胃炎患者66例作为胃炎组。观察两组患者p53和Ki67蛋白表达情况,按不同病理特征将胃癌患者分组并比较p53和Ki67蛋白的表达情况。结果胃癌组患者p53蛋白和Ki67蛋白阳性率高于胃炎组,差异有统计学意义（ P<0.05）;临床分期Ⅰ+Ⅱ期患者p53和Ki67蛋白阳性率低于临床分期Ⅲ+Ⅳ期患者,差异有统计学意义（ P<0.05）;浆膜下浸润患者p53和Ki67蛋白阳性率低于侵及浆膜患者（P<0.05）;有淋巴结转移患者p53蛋白阳性率高于无淋巴结转移患者（P<0.05）,有淋巴结转移患者Ki67蛋白阳性率与无淋巴结转移患者比较,差异无统计学意义（ P>0.05）;按分化程度情况分组,两组患者p53和Ki67蛋白阳性率比较,差异无统计学意义（ P>0.05）。结论 p53和Ki67蛋白在胃癌中的表达率高,具有重要的临床意义。     

利拉鲁肽保护链脲霉素致糖尿病大鼠心肌损伤的机制

目的研究利拉鲁肽对链脲霉素(STZ)致糖尿病大鼠心肌损伤的保护作用机制。方法大鼠腹腔注射STZ构建糖尿病大鼠模型,腹腔注射利拉鲁肽50和200μg·kg~(-1)干预,检测大鼠空腹血糖(FPG)、空腹胰岛素(FINS)和血脂指标情况,应用光、电镜及免疫组化观察心肌组织,并取心肌组织作mRNA及蛋白检测。结果与正常组比较,模型组大鼠的心肌肥厚指数(HWI)、FPG、FINS、总胆固醇(TC)和三酰甘油(TG)水平显著升高,而利拉鲁肽干预后上述指标均显著降低(P<0.05);模型组大鼠心肌细胞及间质胶原纤维排列松散,自噬小体数量显著减少,利拉鲁肽干预后心肌纤维化程度显著降低,自噬小体数量显著升高(P<0.05);模型组大鼠心肌组织中自噬标志因子(LC3B)和腺苷酸活化蛋白激酶(AMPK)磷酸化水平均降低,转化生长因子-β_1(TGF-β_1)和Ⅰ型胶原蛋白(Col-1)的mRNA表达水平以及选择性自噬接头蛋白(p62)、哺乳动物雷帕霉素靶蛋白(mTOR)磷酸化水平均显著升高,利拉鲁肽干预后LC3B和AMPK磷酸化水平均升高,TGF-β_1、Col-1的mRNA表达水平以及p62、mTOR磷酸化水平均显著降低(P<0.05)。结论利拉鲁肽能通过抑制促纤维化因子表达从而抑制心肌组织纤维化,同时促进AMPK/mTOR介导的自噬来改善糖尿病引起的心肌损伤。     

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.