红景天苷对支气管肺炎大鼠Nrf2/Keap1通路及气道炎症的影响

目的 通过构建支气管肺炎SD大鼠实验模型,探究红景天苷对支气管肺炎大鼠核因子红细胞相关因子2（Nrf2）/ Kelch样环氧氯丙烷相关蛋白（Keap1）通路及气道炎症的影响。方法 将SD大鼠随机分为对照组、模型组及红景天苷低、高剂量（30、60 mg/kg）组和鸦胆子苦醇组,红景天苷＋鸦胆子苦醇组,每组10只。红景天苷组大鼠分别ip 30、60 mg/kg红景天苷,鸦胆子苦醇组大鼠ip 100 mg/mL鸦胆子苦醇,红景天苷＋鸦胆子苦醇组ip 60 mg/kg红景天苷和100 mg/mL鸦胆子苦醇。对照组使用同等剂量生理盐水。取各组大鼠肺泡灌洗液,对灌洗液中嗜酸性粒细胞、中性粒细胞和淋巴细胞数量进行分类和计数,ELISA法检测肺泡灌洗液中白细胞介素-1β（IL-1β）、白细胞介素-13（IL-13）、白细胞介素-18（IL-18）水平。苏木精–伊红（HE）染色法观测各组大鼠肺组织形态,Western blotting法检测大鼠肺组织IL-1β、诱导型一氧化氮合酶（iNOS）及Nrf2/Keap1信号通道相关蛋白表达水平。结果 与模型组相比,红景天苷30、60 mg/kg组大鼠肺泡灌洗液中嗜酸性粒细胞、中性粒细胞和淋巴细胞数量,IL-1β、IL-13、IL-18水平及肺组织IL-1β、iNOS、Keap1蛋白表达、炎症评分显著降低,肺组织Nrf2蛋白表达水平显著升高（P＜0.05）;与红景天苷60 mg/kg组相比,红景天苷＋鸦胆子苦醇组大鼠肺泡灌洗液中嗜酸性粒细胞、中性粒细胞和淋巴细胞数量,肺泡灌洗液IL-1β、IL-13、IL-18水平,肺组织IL-1β、iNOS、Keap1蛋白表达水平,炎症评分显著升高,肺组织Nrf2蛋白表达水平显著降低（P＜0.05）。结论 红景天苷可能通过激活Nrf2/Keap1信号通道缓解支气管肺炎炎症。     

褪黑素对帕金森病大鼠Nrf2/HO-1通路及小胶质细胞活化的影响

目的 探讨褪黑素对帕金森病大鼠转录因子NF-E2相关因子2（Nrf2）、血红素加氧酶1（HO-1）的调控作用及其对小胶质细胞活化的影响。方法 取SD大鼠72只,按照随机数字表法分为对照组、模型组、褪黑素（5 mg/kg）组、Nrf2抑制剂全反式维甲酸（ATRA,7 mg/kg）组、Nrf2抑制剂阴性对照（Nrf2-NC）（植物油,10 mL/kg）组、褪黑素＋ATRA（5 mg/kg＋7 mg/kg）组,每组12只。除对照组外,其余各组大鼠通过脑黑质区内注射6-羟多巴胺（6-OHDA）建立帕金森病模型。造模成功后各组开始给药,模型组和对照组ip等量生理盐水,各组连续给药8周,2次/d。末次给药后对大鼠进行行为学评分;免疫组化法检测黑质部多巴胺能神经元及小胶质细胞活化阳性染色细胞数目;免疫荧光共定位检测Nrf2、活化小胶质细胞（IBA1标记）重合表达的细胞数目;酶联免疫吸附法（ELISA）检测黑质部代谢产物α-突触核蛋白（α-Syn）和β淀粉样蛋白（Aβ）。采用Western blotting检测黑质部Nrf2、HO-1、肿瘤坏死因子（TNF-α）、环氧化酶2（COX-2）、小胶质细胞活化特异性标记物（OX-42）蛋白相对表达水平。结果 与对照组比较,模型组大鼠出现单侧或双侧后肢部分瘫痪及行走、进食困难现象,行为学评分显著升高（P<0.05）。与模型组相比,褪黑素组大鼠出现行走时转圈,很少有瘫痪及行走困难症状,且行为评分降低（P<0.05）。ATRA组大鼠单侧或双侧后肢部分瘫痪大鼠例数增多,行为学评分最高（P<0.05）。与对照组相比,模型组大鼠黑质区Nrf2与IBA1重合表达细胞数目、小胶质细胞活化数目、α-Syn和Aβ水平及HO-1、OX-42、TNF-α、COX-2水平和细胞核中Nrf2表达水平升高（P<0.05）,多巴胺能神经元数目减少。与模型组相比,褪黑素组大鼠黑质Nrf2与IBA1重合表达细胞数目、多巴胺能神经元阳性染色数目、HO-1及细胞核中Nrf2表达升高（P<0.05）,小胶质细胞活化数目、α-Syn及Aβ水平、TNF-α、COX-2、OX-42表达降低（P<0.05）;ATRA组黑质区Nrf2与IBA1重合表达细胞数目、多巴胺能神经元数目、HO-1水平及细胞核中Nrf2水平降低（P<0.05）,小胶质细胞活化数目、α-Syn和Aβ水平、TNF-α、COX-2、OX-42表达水平进一步升高（P<0.05）。褪黑素＋ATRA组大鼠上述指标变化与褪黑素组相反（P<0.05）。褪黑素＋ATRA组及Nrf2-NC组上述指标与模型组相比差异无统计学意义。结论 褪黑素可能通过激活Nrf2/HO-1通路,抑制炎症反应及小胶质细胞活化,减少帕金森病大鼠黑质多巴胺能神经元丢失。     

盐酸川芎嗪注射液通过Nrf2/HO-1通路对肝脏缺血再灌注损伤的影响

目的 探讨盐酸川芎嗪注射液对大鼠肝脏缺血再灌注损伤及E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)通路的影响。方法 按随机数字表法将100只大鼠分为假手术组、模型组、丹参注射液(2mL/kg)组、盐酸川芎嗪注射液(30 mg/kg)组和盐酸川芎嗪注射液(30 mg/kg)+鸦胆子苦醇(Nrf2抑制剂,2 mg/kg)组。除假手术组外,各组大鼠采用阻断肝门静脉和肝动脉1h的方法制备肝脏缺血再灌注损伤大鼠模型,造模前30 min ip相应药物。造模6h后,采用生化分析法检测大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)水平;苏木精-伊红(HE)染色法检测肝组织病理学改变;比色法检测肝组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)含量,ELISA法检测肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6含量,Western blotting法检测核因子E2相关因子2/血红素加氧酶1(Nrf2/HO-1)通路相关蛋白表达水平。结果 与模型组比较,丹参注射液组和盐酸川芎嗪注射液组血清ALT、AST、TBIL水平显著降低(P<0.05),肝组织病理学改变明显改善,病理评分显著降低(P<0.05);肝组织SOD、GSH-Px活性显著升高,且MDA、TNF-α、IL-1β、IL-6含量显著降低(P<0.05),Nrf2、HO-1表达量显著升高(P<0.05),胞核核因子-κB(NF-κB)p65表达量及胞核NF-κB p65/胞浆NF-κB p65比值降低(P<0.05)。Nrf2抑制剂鸦胆子苦醇能够明显逆转盐酸川芎嗪注射液对Nrf2/HO-1通路的激活作用以及对大鼠肝脏缺血再灌注损伤的保护作用。结论 盐酸川芎嗪注射液可能通过激活Nrf2/HO-1通路、抑制NF-κB核转位减轻肝脏缺血再灌注损伤大鼠氧化应激和炎症损伤,对肝脏缺血再灌注损伤起到保护作用。     

基于Nrf2/HO-1通路探讨二十五味鬼臼丸对宫颈炎大鼠的治疗作用及机制

目的 研究藏药二十五味鬼臼丸对苯酚胶浆致宫颈炎模型大鼠的治疗作用及机制。方法 将雌性SD大鼠48只随机分为对照组、模型组及二十五味鬼臼丸低、中、高剂量（0.2、0.4、0.8 g·^kg-1）组和抗宫炎片（0.47 g·^kg-1）组，每组8只。除对照组外，其余5组建立25%苯酚胶浆致宫颈炎大鼠模型，各药物组分别以相应药物ig给药，每日1次，连续给药12 d后取材。观察大鼠外阴炎症程度评分、子宫指数、子宫解剖形态学改变；采用苏木精-伊红（HE）染色观察大鼠子宫组织病理学改变；采用酶联免疫吸附测定（ELISA）法检测子宫组织中超氧化物歧化酶（SOD）、丙二醛（MDA）含量变化；采用实时荧光定量PCR（qRT-PCR）法和蛋白免疫印迹（Western blotting）法检测子宫组织中核因子E2相关因子（Nrf2）、血红素氧合酶-1（HO-1）、NADPH氧化酶4（Nox4）的mRNA和蛋白表达情况。结果 与对照组比较，模型组大鼠外阴炎症评分、子宫指数、子宫组织中MDA水平、Nox4的mRNA和蛋白表达均显著升高（P＜0.01），体质量、SOD活性、Nrf2、HO-1的mRNA和蛋白表达均显著降低（P＜0.01），子宫组织出现不同程度的病理变化；与模型组比较，二十五味鬼臼丸能明显降低外阴炎症评分、子宫指数、子宫组织中MDA水平、Nox4的mRNA和蛋白表达（P＜0.05、0.01），升高体质量及子宫组织中SOD活性和Nrf2、HO-1的mRNA和蛋白表达（P＜0.05、0.01），减轻子宫颈炎症损伤程度。结论 二十五味鬼臼丸可能通过抑制Nox4的表达，激活Nrf2/HO-1通路，发挥抗氧化作用，减轻炎症反应，从而抑制宫颈炎发展。     

紫草素对慢性鼻窦炎小鼠鼻黏膜组织炎症反应及SIRT1/Nrf2信号通路的影响

目的 研究紫草素对慢性鼻窦炎小鼠鼻黏膜组织炎症反应及沉默信息调控因子1(SIRT1)/核因子E2相关因子2(Nrf2)信号通路的影响。方法 选取80只小鼠建立慢性鼻窦炎模型后随机分为模型组,紫草素12.5、50.0 mg/kg组,克拉霉素组,每组20只。另取正常饲养的20只小鼠设为假手术组。各组小鼠分别ig给予相应药物,1次/d,共14 d。采用苏木素–伊红（HE）染色观察小鼠鼻黏膜组织病理形态学;Masson染色观察小鼠鼻黏膜组织胶原沉积情况;ELISA法检测小鼠血清中炎性因子水平;Western blotting实验检测小鼠鼻黏膜组织中SIRT1/Nrf2信号通路相关蛋白表达。结果 与模型组比较,紫草素12.5、50.0 mg/kg组小鼠鼻窦黏膜慢性炎症表现和蓝色胶原沉积明显改善;血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-32(IL-32)、γ干扰素（IFN-γ）水平显著降低;鼻黏膜组织中SIRT1、Nrf2、血红素氧合酶-1(HO-1)、NADPH醌氧化还原酶1(NQO-1)蛋白表达水平显著升高（P<0.05）。且紫草素50.0 mg/kg组小鼠上述指标均显著优于紫...     

右美托咪定对高氧诱导急性肺损伤小鼠的保护作用及Nrf2/HO-1通路的影响

摘 要 目的：探讨右美托咪定对高氧诱导急性肺损伤小鼠的保护作用及核转录因子红细胞系2p45相关因子2（Nrf2）/血红素加氧酶 1（HO-1）通路的影响。 方法: 将100只C57BL/6小鼠随机分为5组：正常对照组、模型组、地塞米松组（100 mg·kg-1）、右美托咪定低（40 mg·kg-1）、高（80 mg·kg-1）剂量组。除正常对照组外,其余各组建立高氧诱导急性肺损伤模型,并于造模成功后腹腔注射相应药物,正常对照组和模型组给予等体积生理盐水,qd,持续7 d。实验结束后,检测小鼠肺/体比值、肺损伤评分、血氧分压（PaO2）,小鼠肺组织中Nrf2、HO-1 mRNA及蛋白表达水平,胱天蛋白酶 1（caspase 1）、白细胞介素 1β（IL 1β）、白细胞介素 18（IL 18 ）蛋白水平。制作肺部HE染色切片,观察肺损伤情况。 结果: 与正常对照组比较,模型组肺/体比值、肺损伤评分、Nrf2 mRNA及蛋白表达水平、IL 1β、IL 18、caspase 1蛋白表达水平明显升高,PaO2、HO-1 mRNA及蛋白表达水平明显降低（P<0.05）;与模型组比较,右美托咪定组肺/体比值、肺损伤评分、Nrf2 mRNA及蛋白表达水平、IL 1β、IL 18、caspase 1蛋白表达水平明显降低,PaO2、HO-1 mRNA及蛋白表达水平明显升高（P<0.05）,且呈剂量相关性;右美托咪定低剂量组与地塞米松组比较差异有统计学意义（P<0.05）。正常对照组肺泡组织结构正常,无炎症细胞浸润、无胶原蛋白沉淀;模型组、右美托咪定低剂量组肺泡壁明显增厚、破裂,可见中性细胞及少量嗜酸性细胞浸润,肺间质可见较多胶原蛋白沉淀;右美托咪定高剂量组及地塞米松组肺泡结构基本正常,有少量中性细胞侵润,几乎无胶原蛋白沉淀。 结论: 右美托咪定对高氧诱导急性肺损伤小鼠的保护作用与抑制Nrf2 mRNA及蛋白表达水平表达,进而抑制IL 1β、IL 18、caspase 1蛋白表达有关。     

萝卜硫素对肾小管上皮细胞氧化应激及Nrf2/HO 1信号通路的影响

摘 要 目的：探讨萝卜硫素（SFN）对肾小管上皮细胞（HK-2）的氧化应激及核转录因子E2相关因子2（Nrf2）/血红素加氧酶（HO）-1信号通路的影响。方法: 体外培养HK-2细胞,将细胞分为空白对照组、H2O2处理组、H2O2+10 μmol·K^-1 SFN组、H2O2+20 μmol·K^-1 SFN组和H2O2+40 μmol·K^-1 SFN组;测定HK-2细胞中丙二醛（MDA）、一氧化氮（NO）、谷胱甘肽（GSH）的含量及超氧化物歧化酶（SOD）的活性;RT-PCR和Western Blot法分别检测Nrf2和HO-1 mRNA及蛋白表达水平。结果: 与空白对照组相比,H2O2处理组中MDA、NO含量明显升高,GSH水平和SOD酶活性显著降低（P<0.05）;经高、中、低3种浓度的萝卜硫素处理后MDA、NO含量显著降低,GSH水平显著升高,SOD酶活性也显著升高,Nrf2和HO 1mRNA及蛋白表达明显上调（P<0.05）。结论:萝卜硫素有抗HK 2细胞氧化应激损伤的作用,其作用机制可能与激活Nrf2/HO-1信号通路有关。     

基于cGAS-STING通路探讨知母皂苷元对脂多糖诱导的小鼠急性肺损伤保护作用

目的 研究知母皂苷元对脂多糖（LPS）诱导的小鼠急性肺损伤的保护作用。方法 将昆明小鼠随机分为对照组、模型组、地塞米松（0.5 mg/kg）组、知母皂苷元（50、100、200 mg/kg）组。知母皂苷元50、100、200 mg/kg组小鼠ig相应剂量知母皂苷元溶液,地塞米松组小鼠ip地塞米松磷酸钠注射液,对照组和模型组小鼠ig等体积生理盐水,1次/d,连续7 d。末次给药1 h后,其余各组小鼠除对照组外均ip 10 mg/kg LPS溶液复制小鼠急性肺损伤模型。6 h后取各组小鼠左肺组织,计算肺湿/干质量比（W/D）;采用苏木精-伊红（HE）染色法观察肺组织病理形态学变化;采用酶联免疫吸附测定法（ELISA）检测血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平;采用Western blotting法检测肺组织中鸟苷酸-腺苷酸合成酶（cGAS）、干扰素基因刺激因子（STING）的蛋白表达。结果 与模型组相比,知母皂苷元组小鼠左肺W/D值、血清中IL-6和TNF-α水平、肺组织中cGAS和STING的蛋白表达均显著降低（P<0.05）,肺组织病理学损伤均有所改善。结论 知母皂苷元可能通过抑制cGAS-STING通路,减少炎症因子TNF-α、IL-6的分泌,从而保护LPS诱导的急性肺损伤。     

基于Nrf 2/HO 1/NF-κB通路探讨栀黄止痛散汤对急性痛风性关节炎大鼠的保护作用

摘 要 目的：探究栀黄止痛散汤对痛风性关节炎（AGA）大鼠的保护作用以及对NF E2相关因子2（Nrf 2）/血红素氧合酶 1/（HO 1）/核转录因子κB（NF-κB）通路的影响。 方法: 采用随机数字表法将90只SD大鼠分为正常对照组、模型组（踝关节腔注射尿酸钠复制AGA大鼠）、栀黄止痛散汤低（2.5 g·kg-1）、中（5 g·kg-1）、高（10 g·kg-1）剂量组、阳性对照组（秋水仙碱 1 mg·kg-1）,每组15只。酶联免疫法（ELISA）检测关节液中白细胞介素 6(IL 6)、肿瘤坏死因子 α(TNF α)、白细胞介素 1β(IL 1β)、超氧化物歧化酶（SOD）、丙二醛（MDA）水平,造模后对大鼠步态、关节炎症指数进行分级评定,于造模前以及造模后6,12,24,48 h采用容积测定法检测裸关节肿胀度;苏木精 伊红染色法（HE）观察踝关节组织形态学变化情况,实时荧光定量PCR（RT PCR）测定关节组织中Nrf 2、HO 1mRNA表达,免疫印迹法（WB）测定关节组织中Nrf 2、HO 1、P P65、P65、P IKBa、IKBa蛋白表达。 结果: 与正常对照组相比,模型组大鼠步态、关节炎症指数分级、6,12,24,48 h关节肿胀度、关节液中TNF α、IL 6、IL 1β、MDA水平、关节组织中P P65、P IKB蛋白表达显著升高,SOD水平及Nrf 2、HO 1 mRNA和蛋白表达显著降低（P＜0.05）。与模型组相比,栀黄止痛散汤组和阳性对照组大鼠步态、关节炎症指数分级、6,12,24,48 h关节肿胀度、关节液中TNF α、IL 6、IL 1β、MDA水平、关节组织中P P65、P IKB蛋白表达显著降低,SOD水平及Nrf 2、HO 1 mRNA和蛋白表达显著升高,且栀黄止痛散汤组具有剂量依赖性（P＜0.05）。结论: 栀黄止痛散汤能够降低AGA大鼠关节炎症反应,缓解关节肿胀,其可能通过激活Nrf 2/HO 1/NF-κB通路来实现。     

芹菜素对百草枯致小鼠肺纤维化保护作用及机制研究

目的 研究芹菜素对百草枯致小鼠肺纤维化的保护作用及机制。方法 将小鼠随机分为对照组、模型组、地塞米松组（1 mg/kg）和芹菜素低、高剂量（10、20 mg/kg）组,除对照组外,其他各组ip百草枯（50 mg/kg）建立小鼠肺纤维化模型,第8天开始ig给药,连续给药21 d。观察小鼠体质量变化;测量小鼠肺系数;采用HE染色观察肺组织形态学变化;免疫组化法观察小鼠肺组织中Ⅰ、Ⅲ型胶原表达变化;ELISA法检测各组小鼠肺组织中Ⅰ、Ⅲ型胶原和炎症因子肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-1β含量;Western blotting法测定肺组织Caveolin-1蛋白表达水平。结果 造模第28天时,与模型组比较,芹菜素低、高剂量组小鼠体质量显著增加（P<0.05）;地塞米松组和芹菜素低、高剂量组肺系数显著降低（P<0.05）;芹菜素低、高剂量组肺组织内炎性细胞浸润较少、肺泡壁断裂及肺泡腔融合较少,肺纤维化程度较轻;芹菜素低、高剂量组和地塞米松组小鼠的肺组织中Ⅰ、Ⅲ型胶原和IL-6、IL-1β、TNF-α含量显著下降（P<0.01）,Caveolin-1蛋白表达显著下降（P<0.01）。结论 芹菜素对百草枯诱导小鼠肺纤维化具有保护作用,其机制可能与Ⅰ、Ⅲ型胶原含量及炎症因子水平下调、Caveolin-1蛋白表达水平下调相关。     

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.