利舒康胶囊对模拟高原缺氧动物的保护作用研究

目的 研究利舒康胶囊的抗缺氧活性及其对模拟高原缺氧大鼠脑组织的保护作用。方法 采用小鼠常压密闭缺氧耐受力实验和小鼠急性减压缺氧耐受力实验联合评价利舒康胶囊的抗缺氧活性;采用低压氧舱模拟海拔8 000 m高原环境,观察缺氧前后大鼠脑组织病理显微结构的改变,并测定其中能量代谢和抗氧化应激相关指标。结果 利舒康胶囊低、中、高剂量组均能有效延长常压密闭缺氧小鼠的存活时间（P<0.01）,且存在剂量依赖性,其中,中、高剂量组明显优于红景天胶囊组（P<0.05或P<0.01）;利舒康胶囊低、中、高剂量组能够降低急性减压缺氧小鼠的死亡率（P<0.01）,且具有剂量依赖性,其中,中、高剂量组的死亡率明显低于红景天胶囊组（P<0.01）;低压氧舱模拟高原减压缺氧实验结果显示,与正常对照组相比,减压缺氧后大鼠脑组织出现病理性损伤,脑组织中丙二醛（malondialdehyde,MDA）、过氧化氢（hydrogen peroxide,H₂O₂）、一氧化氮（nitric oxide,NO）、乳酸（lactic acid,LD）含量和乳酸脱氢酶（lactic dehydrogenase,LDH）活性显著升高（P<0.05或P<0.01）,超氧化物歧化酶（superoxide dismutase,SOD）、过氧化氢酶（catalase,CAT）、谷胱甘肽过氧化物酶（glutathion peroxidase,GPX）活性均显著降低（P<0.05或P<0.01）,而经利舒康胶囊预处理后,大鼠脑组织的病理损伤有所缓解,脑组织中MDA、NO含量均显著下降（P<0.05或P<0.01）,中、高剂量组H₂O₂、LD含量及LDH活性显著下降（P<0.05或P<0.01）,高剂量组SOD、CAT、GPX活性均显著升高（P<0.05）。结论 利舒康胶囊具有良好的抗高原缺氧活性,能够对模拟高原缺氧损伤大鼠起到保护作用,其机制可能与提高机体抗氧化能力,降低自由基损伤,缓解缺氧所致能量缺乏和代谢障碍有关。     

苯甲酰乌头原碱配伍芍药苷的抗炎镇痛作用研究

目的 探讨不同剂量苯甲酰乌头原碱配伍芍药苷的抗炎镇痛作用。方法 通过小鼠耳肿胀试验、大鼠足肿胀试验、小鼠热板试验和小鼠扭体试验,研究不同剂量苯甲酰乌头原碱配伍芍药苷的抗炎镇痛作用。结果 苯甲酰乌头原碱配伍芍药苷（高剂量配伍组）可显著抑制二甲苯所致的小鼠耳廓肿胀（P<0.05）。在1 h时,苯甲酰乌头原碱配伍芍药苷可显著抑制大鼠足肿胀（P<0.05或<0.01）;在2 h时,中、高剂量配伍组可显著抑制大鼠足肿胀（P<0.05或<0.01）,其中高剂量配伍组相对于芍药苷组和苯甲酰乌头原碱高剂量组,大鼠足肿胀显著减轻（P<0.05）;在4 h时,中、高剂量配伍组可显著抑制大鼠足肿胀（P<0.05或<0.01）,高剂量配伍组相对于芍药苷组,大鼠足肿胀显著减轻（P<0.05）。在1 h和1.5 h时,高剂量配伍组可显著升高小鼠热刺激疼痛的痛阈值（P<0.05）。高剂量配伍组可显著升高小鼠冰醋酸刺激疼痛的痛阈值（P<0.05）。苯甲酰乌头原碱配伍芍药苷可显著减少冰醋酸刺激引起的小鼠扭体次数（P<0.01）,其中高剂量配伍组相对于芍药苷组和苯甲酰乌头原碱高剂量组,小鼠扭体次数显著减少（P<0.01）。结论 苯甲酰乌头原碱配伍芍药苷可增加苯甲酰乌头原碱、芍药苷的抗炎镇痛作用。     

钩藤人参合用对高血压合并心衰大鼠模型的影响

目的 研究钩藤人参合用对高血压合并心衰（HCHF）模型大鼠的影响。方法 将大鼠随机分为假手术组、模型组、卡托普利组（0.014 3 g/kg）和钩藤人参合用高（钩藤0.9 g/kg+人参1.8 g/kg）、中（钩藤0.45 g/kg+人参0.9 g/kg）,低（钩藤0.225 g/kg+人参0.45 g/kg）剂量组。采用腹主动脉缩窄术制作大鼠HCHF模型,5周后通过大鼠尾动脉压监测仪评估造模是否成功,其中假手术组只分离腹主动脉,不结扎。酶联免疫吸附法（ELISA）测定大鼠血清B型脑钠肽（BNP）、血管紧张素Ⅱ （Ang Ⅱ）、血管紧张素1型受体（AT₁）、β1肾上腺素受体（β1-AR）水平。取心脏测定心脏质量指数（HWI）,HE染色法观察大鼠心肌纤维排列状况。结果 造模第5周后手术各组收缩压较对照组显著升高（P<0.01）,验证模型成功;给药第2、4周,钩藤人参合用中、高剂量组收缩压较模型组显著下降（P<0.05、0.01）。与模型组比较,钩藤人参合用中、高剂量组能显著降低心衰大鼠的HWI以及AT₁、Ang Ⅱ、BNP的浓度,显著升高β1-AR浓度（P<0.05、0.01）,且呈剂量相关性。光镜下观察模型组心肌结构紊乱,心肌细胞排列呈波浪状,心肌纤维断裂严重;卡托普利组和人参钩藤高剂量组可见心肌结构排列较均匀,心肌细胞形态正常,心肌纤维略有断裂。结论 钩藤人参合用对于降低大鼠血压,改善大鼠心衰症状效果显著,且呈剂量相关性,其中高剂量与卡托普利组效果相当。     

牡荆素调控PI3K/Akt通路对脑外伤大鼠的神经保护作用研究

目的 通过磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）信号通路探讨牡荆素对脑外伤大鼠的神经保护作用。方法 选用SD大鼠90只,随机分成假手术组,模型组,牡荆素假手术组（12 mg/kg牡荆素）,牡荆素低（3 mg/kg牡荆素）、高剂量组（12 mg/kg牡荆素）和吡拉西坦组（20 mg/kg吡拉西坦）,每组18只。采用自由落体致伤法建立脑外伤大鼠模型;采用神经功能评分法评价神经功能缺损程度;测定脑组织的含水量;苏木素伊红（HE）染色检测脑组织病理变化;TUNEL法检测脑组织神经细胞的凋亡情况;ELISA法检测脑组织丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）水平;Western blotting法检测脑组织中PI3K、p-PI3K、Akt、p-Akt、mTOR、p-mTOR蛋白水平。结果 与假手术组相比,模型组大鼠神经元变性坏死,毛细血管破裂,可见大量出血、炎性细胞浸润,神经功能受损评分、细胞凋亡指数、脑组织含水量及MDA含量显著升高（P<0.05）,SOD、GSH-Px含量及p-PI3K、p-Akt、p-mTOR蛋白水平显著降低（P<0.05）。与模型组相比,牡荆素低、高剂量组和吡拉西坦组大鼠病理变化均有一定程度减轻,神经功能受损评分、细胞凋亡指数、脑组织含水量及MDA含量显著降低（P<0.05）,SOD、GSH-Px含量及p-PI3K、p-Akt、p-mTOR蛋白水平均显著升高（P<0.05）。假手术组和牡荆素假手术组各项指标差异无统计学意义。牡荆素高剂量组和吡拉西坦组各项指标差异无统计学意义。结论 牡荆素可能通过激活PI3K/Akt信号通路,发挥脑外伤大鼠的神经保护作用。     

不同来源黄芩炮制品的解热作用比较研究

目的 比较二倍体黄芩、四倍体黄芩、甘肃黄芩的解热作用。方法 将Wistar大鼠110只,随机分为11组。药物组分别给予不同来源的黄芩生品、酒炙品水煎液灌胃,连续给药2 d。第3天,除空白组外,其余各组大鼠腹腔注射脂多糖100 μg·kg^-1造模。2 h后,继续灌胃1次。造模1,2,3,4 h分别检测大鼠肛温,动物处死后采血,检测大鼠血清中IL-1β、PGE₂含量。结果 与模型组比较,黄芩各药物组大鼠在造模2,3,4 h时ΔT显著低于模型组,且大鼠血清中IL-1β、PGE₂含量显著降低（P<0.05）;与道地产区河北产黄芩组比较,甘肃黄芩Ⅰ组（生品）、Ⅱ组（酒炙品）大鼠2,3,4 h时ΔT均显著高于河北产黄芩组（P<0.05）;同时,二倍体黄芩、四倍体黄芩、甘肃黄芩的Ⅰ组（生品）、Ⅱ组（酒炙品）大鼠血清中IL-1β、PGE₂含量均显著高于河北产黄芩Ⅰ组、Ⅱ组（P<0.05）。结论 二倍体黄芩、四倍体黄芩、甘肃黄芩均有解热作用,但甘肃黄芩解热作用与道地黄芩有一定差异。不同来源黄芩生品与酒炙品对发热大鼠的解热作用无显著性影响。     

荜铃胃痛颗粒抗实验性胃溃疡作用研究

目的 探究荜铃胃痛颗粒对乙醇诱导胃溃疡模型大鼠的保护作用。方法 SD大鼠随机分为对照组、模型组及荜铃胃痛颗粒低、中、高剂量（0.79、1.58、3.16 g·kg^-1）组和西咪替丁（42.00 mg·kg^-1,阳性药）组,每组8只;各组均按剂量预给药8 d,对照组和模型组大鼠ig等体积0.5%羧甲基纤维素钠（CMC-Na）溶液。末次给药30 min后,除对照组外,其余大鼠ig给予1 mL无水乙醇造模,1 h后牺牲动物取材;展开胃黏膜面拍照,测量溃疡面积,取部分胃组织进行HE染色;检测血清中白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和超氧化物歧化酶（SOD）水平,检测胃组织中髓过氧化物酶（MPO）和前列腺素E₂（PGE₂）水平。结果 与对照组比较,模型组大鼠胃溃疡面积和胃黏膜病理评分显著升高（P<0.001）,大鼠血清中IL-1β（P<0.01）和TNF-α（P<0.05）水平均显著升高,大鼠胃组织MPO活力显著升高（P<0.001）,大鼠胃组织中PGE₂水平显著降低（P<0.01）。与模型组比较,各给药组大鼠胃溃疡面积和胃黏膜病理评分显著降低（P<0.05、0.01、0.001）。与模型组比较,荜铃胃痛颗粒组大鼠血清IL-1β和TNF-α水平显著降低（P<0.05、0.001）,胃组织中MPO活力显著降低（P<0.01、0.001）,血清SOD活力显著升高（P<0.05）;胃组织PGE₂水平显著增加（P<0.05）。结论 荜铃胃痛颗粒可通过抑制炎症因子分泌、缓解机体氧化应激、保护胃黏膜等发挥对胃溃疡模型大鼠的保护作用。     

愈风宁心片对偏头痛大鼠模型的镇痛作用研究

目的 探讨愈风宁心片对偏头痛大鼠模型的镇痛作用及机制。方法 SD大鼠随机分成6组：对照组、模型组、苯甲酸利扎曲普坦片（阳性药,0.9 mg·kg^-1）组和愈风宁心片低、中、高剂量（378、756、1 512 mg·kg^-1）组,每天ig给药1次,连续10 d。末次给药后1 h,除对照组外,其余各组大鼠在头颈处sc 10 mg·kg^-1硝酸甘油建立偏头痛大鼠模型,观察疼痛行为学指标,试剂盒法检测血清中疼痛相关因子缩胆囊素（CCK）、白细胞介素-1β （IL-1β）、前列腺素E（2 PGE₂）含量;利用小鼠醋酸扭体实验、小鼠右后足跖部福尔马林致痛实验观察愈风宁心片低、中、高剂量（546、1 092、2 184 mg·kg^-1）对小鼠扭体反应和舔足时长的影响。结果 偏头痛实验结果表明,与模型组比较,愈风宁心片各剂量组和苯甲酸利扎曲普坦片组的挠头、甩头次数和行为学评分显著降低（P<0.05、0.01）;愈风宁心片中、高剂量组血清CCK水平显著降低（P<0.05、0.01）,低、中、高剂量组血清PGE₂、IL-1β水平显著降低（P<0.05、0.01）。醋酸扭体实验结果表明,与模型组比较,愈风宁心片中、高剂量组小鼠扭体次数显著降低（P<0.05、0.01）,高剂量组小鼠扭体反应潜伏期显著延长（P<0.01）。福尔马林致痛实验结果表明,与模型组比较,各给药组均能显著缩短小鼠的舔足时长（P<0.01）。结论 愈风宁心片对偏头痛模型具有镇痛作用,其机制可能与调节中枢及外周神经系统、改善疼痛相关因子含量有关。     

益气活血风静胶囊对大鼠及家兔血液流变学的影响

目的：研究益气活血风静胶囊对大鼠及家兔的血液流变学的影响。方法：采用SD大鼠及家兔分别灌胃给药14 d及10 d,检测SD大鼠及家兔血浆凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、纤维蛋白原（FIB）及血小板聚集率。另采用SD大鼠,大脑中动脉阻塞（MCAO）大鼠造模后灌胃给药5 d,检测MCAO大鼠PT、APTT、TT、FIB及脑组织含水量。结果：与空白组比较,益气活血风静胶囊高、中剂量组及阳性对照组,能显著延长大鼠血浆的PT、TT、APTT （P<0.05）,并能显著降低FIB的含量（P<0.05或P<0.01）,显著降低以二磷酸腺苷（ADP）诱导的大鼠血小板聚集率（P<0.05）。与空白组比较,益气活血风静胶囊高、中、低剂量组及阳性对照组能显著延长家兔血浆的PT、TT、APTT （P<0.05或P<0.01）,并能显著降低FIB的含量（P<0.01）,显著降低以ADP诱导的大鼠血小板聚集率（P<0.05或P<0.01）。MACO大鼠模型组给药后,与假手术组比较,模型组大鼠PT、APTT、TT明显缩短（P<0.05）,FIB含量升高（P<0.05）,脑组织含水量明显增加（P<0.01）;与模型组比较,益气活血风静组和人参有效部位组能延长大鼠血浆PT、APTT、TT时间（P<0.05或P<0.01）,降低纤维蛋白原的含量（P<0.01）,显著降低模型大鼠脑组织含水量（P<0.05）,牡丹皮有效部位组大鼠TT延长（P<0.05）,降低纤维蛋白原的含量（P<0.01）,显著降低模型大鼠脑组织含水量（P<0.05）。结论：益气活血风静胶囊具有显著的抗凝血以及抑制以ADP诱导的血小板聚集的作用,并对MCAO大鼠有较好的活血作用。     

肾衰宁胶囊对慢性肾脏病合并高磷血症大鼠的药效学研究

目的 研究肾衰宁胶囊对慢性肾脏病合并高磷血症大鼠模型的改善作用。方法 选择90只雄性SD大鼠,腺嘌呤联合高磷饮食诱导慢性肾脏病合并高磷血症大鼠模型,依据血磷水平及肾损伤程度分为模型组（16只）、司维拉姆组（阳性药,掺食法给予3%碳酸司维拉姆片,14只）和肾衰宁低、中、高剂量组（ig给予肾衰宁胶囊400、600、800 mg·kg^-1,低剂量组15只,高、中剂量组分别有16只）,另设对照组（正常饲料喂养）,连续给药5周。将各组大鼠置于代谢笼中24 h,记录饮水及饮食量,收集各组大鼠24 h尿液及粪便,记录大鼠的尿量、粪便排泄量;试剂盒法测定动物血清磷、钙、肌酐、尿素氮、成纤维细胞生长因子23（FGF-23）、1,25-二羟基维生素D[1,25（OH）₂D]、甲状旁腺激素（PTH）、碱性磷酸酶活力（ALP）水平,计算钙磷乘积;取肾脏称质量、计算肾脏指数,肾脏组织HE、Masson病理染色评价损伤程度;体外磷结合实验检测在pH 3、5、7、8条件下肾衰宁（2.75、5.50、13.75 mg·mL^-1）是否与磷结合。结果 与模型组比较,肾衰宁低、高剂量组日饮食量、24 h排便量、24 h排便颗粒显著升高（P<0.05、0.001）,低、中、高剂量组日饮水量显著降低（P<0.05、0.01）,高剂量组24 h排尿量显著降低（P<0.05）;低、高剂量组血清磷水平、钙磷乘积显著降低（P<0.01、0.001）;高剂量组血清肌酐水平显著降低（P<0.05）,低、高剂量组血清尿素氮水平显著降低（P<0.05、0.01）;各剂量组肾脏外观明显改善,高剂量显著改善肾脏病理损伤程度（P<0.01）;高剂量组FGF-23、PTH、ALP水平显著降低（P<0.05、0.01、0.001）,1,25（OH）₂D水平均显著升高（P<0.001）;体外磷结合实验未出现肾衰宁结合磷的现象。结论 肾衰宁胶囊可以改善模型动物的钙磷代谢紊乱,改善肾损伤,调节钙磷代谢相关激素水平。     

间充质干细胞注射液对大鼠膝骨关节炎的影响

目的 研究间充质干细胞注射液（MSCsI）对手术法诱导的大鼠膝骨关节炎的治疗作用。方法 自70只大鼠中随机取8只为假手术组，其余62只动物均进行右侧膝关节单侧手术造模。术后4周，进行X光检查并进行K-L评分，选择模型成功、状态良好的模型动物40只，根据K-L评分随机分为模型组、玻璃酸钠（阳性药，每关节腔0.5 mg玻璃酸钠注射液）组和MSCsI低、中、高剂量（每关节腔1.5×10⁵、5.0×10⁵、1.5×10⁶个细胞）组，每组8只。分组后次日开始，玻璃酸钠组每周1次，其余各组每2周1次，关节腔内注射给药，持续5周，假手术组与模型组给予等体积0.9%氯化钠溶液。使用X射线机检测大鼠膝关节病变；给药后记录大鼠行为学及痛阈变化；剖杀时记录关节软骨大体评分；试剂盒法检测血清中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、转化生长因子β（TGF-β）、II型胶原C端肽（CTX-Ⅱ）、前列腺素E₂（PGE₂）水平；取膝关节组织进行病理切片，HE染色、甲苯胺蓝染色观察组织损伤。结果 与模型组相比，MSCsI高剂量显著降低大鼠X光评分（P<0.05）、降低大鼠关节软骨大体观察评分（P<0.05）；给药4周后，MSCsI低、中、高剂量显著降低大鼠行为学评分（P<0.05、0.01），中、高剂量显著升高大鼠痛阈值（P<0.01）；MSCsI低剂量显著降低血清中IL-1β水平、升高TGF-β水平（P<0.05），中剂量显著降低血清中IL-1β、IL-6、CTX-Ⅱ水平、升高TGF-β水平（P<0.05、0.01），高剂量显著降低血清中IL-1β、IL-6、CTX-Ⅱ、PGE₂水平、升高TGF-β水平（P<0.05、0.01）；HE染色结果显示，MSCsI各剂量能有效减轻模型大鼠组织病理学改变，滑膜、软骨及软骨下骨病变较轻；甲苯胺蓝染色显示，MSCsI各剂量可减小模型大鼠软骨基质损伤。结论 MSCsI每2周1次关节腔内注射对手术诱导的大鼠膝骨关节炎有明显的治疗作用。     

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.     

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.