银甲片通过纠正外周血Th17/Treg平衡改善慢性输卵管炎大鼠不孕

目的 探讨银甲片是否通过纠正外周血Th17/Treg平衡改善慢性输卵管炎大鼠不孕。方法 100只雌性Wistar大鼠，其中82只构建慢性输卵管炎大鼠模型，造模成功后，取80只随机分为模型组、左旋氧氟沙星组(20 mg·kg^-1)、银甲片低剂量组(0.38 g·kg^-1·d^-1)、银甲片中剂量组(0.76 g·kg^-1·d^-1)、银甲片高剂量组(1.52 g·kg^-1·d^-1)，每组16只，另取16只设为空白对照组。治疗组分别按不同剂量灌胃给药，模型组与空白对照组灌服等量生理盐水(20 mL·kg^-1·d^-1)，每日1次，灌胃7 d后停药1 d，7 d为1个周期，共灌胃3个周期。给药结束后，观察大鼠受孕情况，采集血样和输卵管组织。采用HE染色观察输卵管组织病理变化；透射电镜观察输卵管组织超微结构变化；ELISA检测血清中TNF-α、IL-6含量；流式细胞术检测外周血Treg、Th17细胞比例；RT-qPCR和Western blotting检测输卵管组织IL-17、IL-10、Foxp3、RORγt mRNA及蛋白表达。结果 与空白对照组相比，模型组大鼠输卵管纤毛、微绒毛稀疏，线粒体肿胀；且TNF-α、IL-6含量、Th17细胞比例及输卵管组织IL-17、RORγt mRNA和蛋白表达明显升高，大鼠受孕率、IL-10、Treg细胞比例及Foxp3 mRNA和蛋白表达明显降低(P<0.05)。与模型组比较，银甲片高剂量组改善大鼠输卵管结构；明显降低模型大鼠TNF-α、IL-6含量、Th17细胞比例及输卵管组织IL-17、RORγt mRNA和蛋白表达；明显升高大鼠受孕率及IL-10、Treg细胞比例和Foxp3 mRNA和蛋白表达(P<0.05)。结论 银甲片可有效地调节Th17/Treg平衡，进而调节Treg和Th17细胞介导的炎性反应，提高慢性输卵管模型大鼠受孕率。     

绞股蓝总皂苷对非酒精性脂肪肝大鼠Treg/Th17免疫功能的影响

目的 研究绞股蓝总皂苷对非酒精性脂肪肝（nonalcoholic fatty liver disease,NAFLD）大鼠肝脏保护作用及免疫调节作用机制。方法 48只SD大鼠随机分为正常对照组,模型对照组,多烯磷脂酰胆碱胶囊组（阳性对照组,150 mg·kg^-1）及绞股蓝总皂苷高、中、低（240,120,60 mg·kg^-1）剂量组,除正常对照组外,其余各组连续饲喂高脂饲料10周,制备NAFLD模型;模型成功后,各组连续给药8周。实验期间,分别于给药0,4,8周眼眶取血检测血清AST、ALT;末次给药后,采用流式细胞技术检测外周血Th17和Treg细胞含量;酶联免疫法检测血清IL-17、IL-10及TNF-α含量。HE染色检查肝组织病理变化和免疫组化法检查肝组织IL-17和Foxp3表达。结果 给药4周,绞股蓝总皂苷高剂量显著降低大鼠血清ALT、AST（P<0.01）;给药8周,绞股蓝总皂苷各剂量均能显著降低血清ALT、AST（P<0.05,0.01）。绞股蓝总皂苷高、中剂量能改善肝组织病变,降低TNF-α水平;高剂量显著降低IL-17、升高IL-10水平（P<0.05,0.01）,降低淋巴细胞IL-17含量,升高CD4⁺CD25⁺Treg含量（P<0.05）,明显减少炎症因子IL-17的表达和增加Foxp3表达。结论 绞股蓝总皂苷能改善NAFLD大鼠肝脏病变,其作用机制可能与调节肝脏Treg/Th17细胞平衡,减少促炎症因子和增加抗炎因子产生相关。     

IL-35 Th17/Treg失衡在系统性红斑狼疮中的表达与意义

目的 分析系统性红斑狼疮（SLE）患者血清白细胞介素-35（IL-35）水平、外周血辅助性T细胞17（Th17）和调节性T细胞（Treg）的变化,探讨IL-35及Th17/Treg失衡在SLE发展中的作用。方法 选取2019年1月至4月在南京鼓楼医院就诊的54例新发SLE患者为研究对象,根据SLE疾病活动度（SLEDAI）分为轻度活动组,26例;中度活动组,10例;重度活动组,18例。另外选择同时期体检中心健康体检者30例作为对照组。用酶联免疫吸附法（ELISA）检测4组研究对象血清IL-35水平,流式细胞术检测外周血Th17与Treg细胞占T细胞的比例,比较4组血清IL-35及外周血Treg、Th17、Th17/Treg表达水平,并采用Pearson相关性分析IL-35与Treg、Th17、Th17/Treg和SLEDAI的相关性。结果 SLE组患者Th17细胞百分比、Th17/Treg比值均高于对照组,IL-35水平、Treg细胞百分比均低于对照组,差异均有统计学意义（P<0.05）。重度活动组Th17细胞百分比高于中度活动组,中度活动组高于轻度活动组,差异均有统计学意义（P<0.05）;3组SLE患者Treg细胞百分比比较,差异无统计学意义（P>0.05）;中度活动组IL-35水平低于轻度活动组,而Th17/Treg高于轻度活动组,差异均有统计学意义（P<0.05）,重度活动组与中度活动组IL-35、Th17/Treg表达比较,差异无统计学意义（P>0.05）。Pearson相关性分析显示,SLE患者IL-35水平与Treg呈显著正相关（r=0.373,P=0.006）,与Th17、Th17/Treg和SLEDAI呈负相关（r=-0.563,-0.480,-0.686,P<0.001）。SLE患者经过短暂治疗后IL-35与Treg表达较治疗前升高,Th17与Th17/Treg的表达较治疗前降低,差异均有统计学意义（P<0.05）。结论 SLE患者体内血清IL-35水平降低,并与SLE患者病情活动相关;低表达的IL-35可能参与了Th17/Treg的失衡,促进SLE的形成。     

他克莫司对白癜风小鼠Th17/Treg细胞平衡及黑素细胞丢失的影响

目的 探究他克莫司对白癜风小鼠辅助性T17（Th17）/调节性T （Treg）细胞平衡和黑素细胞丢失的影响。方法 将小鼠随机分为对照组、模型组和他克莫司低、中、高剂量组（涂抹10、50、100 mg 0.03%他克莫司软膏）,使用松香/蜡混合物对小鼠背部相同位置进行去毛,大小为2 cm×2 cm,将其分为两部分：用药区域与非用药区域,面积1：1。除对照组外,于小鼠背部用药区均匀涂抹50 mg 40%莫诺苯宗软膏,每天1次,连续90 d,制备白癜风模型。莫诺苯宗涂抹30 d后开始于相同位置涂抹他克莫司软膏,2种药膏涂抹时间间隔7 h,他克莫司软膏每天早晚各涂抹1次,连续用药60 d。肉眼观察小鼠皮毛脱色情况并进行脱色评分,通过反射式共聚焦显微镜（RCM）观察小鼠皮肤黑素细胞和黑色素的分布,取小鼠皮损进行苏木精-伊红染色（HE）和马松染色（MF）对基底层黑素细胞和含黑色素的毛囊进行计数,通过流式细胞术测定小鼠外周血中Th17和Treg淋巴细胞的比例,酶联免疫吸附试验（ELISA）检测外周血白细胞介素-17（IL-17）、IL-22和叉头型基因p3（Foxp3）的含量。结果 与对照组比较,白癜风模型组小鼠用药区皮毛明显脱色,脱色评分显著升高（P<0.05）,皮损处色素明显缺失;含黑色素的毛囊和黑素细胞显著减少（P<0.05）;Th17/Treg淋巴细胞比例显著升高（P<0.05）;血清IL-17、IL-22水平显著上升,Foxp3水平显著降低（P<0.05）。与模型组比较,他克莫司各组小鼠皮毛脱色情况明显改善,脱色评分显著降低（P<0.05）,皮损处可见色素分布及黑素细胞;含黑色素的毛囊和黑素细胞显著增多（P<0.05）;Th17/Treg淋巴细胞比例显著降低（P<0.05）;IL-17、IL-22水平显著降低,Foxp3水平显著升高（均P<0.05）。结论 他克莫司可调控白癜风小鼠Th17/Treg淋巴细胞平衡,抑制其黑素细胞丢失。     

芪倍合剂联合美沙拉嗪对活动期溃疡性结肠炎患者Th17、Treg细胞及其相关细胞因子水平的影响

目的 探讨芪倍合剂联合美沙拉嗪治疗活动期溃疡性结肠炎的临床疗效和其对Th17、Treg细胞及其相关细胞因子水平的影响。方法 选取2019年1月—2019年12月于新乡医学院第一附属医院就诊的142例活动期溃疡性结肠炎患者作为研究对象,将所有患者随机分为对照组和观察组,每组各71例。对照组口服美沙拉嗪肠溶片,1 g/次,4次/d;观察组在对照组治疗的基础上口服芪倍合剂,50 mL/次,3次/d。两组疗程均为8周。观察两组患者的临床疗效,同时比较两组治疗前后的Mayo评分、Baron评分、Th17细胞、Treg细胞、Th17/Treg细胞比值、白细胞介素（IL）-17、IL-23、转化生长因子（TGF-β）和IL-10水平。结果 治疗后,对照组和观察组的总有效率分别为81.69%、94.36%,两组总有效率比较差异具有统计学意义（P<0.05）。治疗后,两组Mayo评分和Baron评分均显著降低（P<0.05）;且观察组Mayo评分和Baron评分显著低于对照组（P<0.05）。治疗后,两组患者Th17细胞、Th17/Treg细胞比值水平均显著下降,而Treg细胞显著升高（P<0.05）。治疗后,与对照组相比,观察组Th17细胞和Th17/Treg细胞比值显著降低,而Treg细胞显著升高（P<0.05）。治疗后,两组血清IL-17和IL-23水平显著降低,而TGF-β和IL-10水平显著升高（P<0.05）。治疗后,观察组血清IL-17、IL-23水平显著低于对照组,而TGF-β和IL-10水平显著高于对照组（P<0.05）。结论 芪倍合剂联合美沙拉嗪对活动期溃疡性结肠炎临床疗效较好,治疗安全性高,能有效改善患者的临床症状,可能机制与其能显著改善Th17/Treg细胞平衡有关。     

参芪肝康片联合恩替卡韦治疗慢性乙型肝炎的临床研究

目的 探讨参芪肝康片联合恩替卡韦治疗慢性乙型肝炎患者的临床疗效。方法 选取2017年6月—2019年6月于新乡医学院第一附属医院感染科住院治疗的114例慢性乙型肝炎患者作为研究对象,按照住院时间和治疗方式差异随机将患者分为对照组（n=57）和观察组（n=57）。对照组口服抗病毒药物马来酸恩替卡韦片,0.5 mg/次,1次/d。观察组在对照组治疗的基础上口服参芪肝康片治疗,2.1 g/次,3次/d。两组疗程均为6个月。观察两组患者的临床疗效,比较两组治疗前后的肝功能指标、Th17细胞频率、Treg细胞频率、Th17/Treg细胞频率比值、白细胞介素-17（IL-17）、转化生长因子-β（TGF-β）水平以及不良反应发生率。结果 治疗后,对照组和观察组总有效率分别为77.19%和92.98%,两组比较差异具有统计学意义（P<0.05）。与治疗前相比,两组丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（TBIL）水平均显著降低,差异均具有统计学意义（P<0.05）;与对照组相比,观察组治疗后血清ALT、AST和TBIL均显著降低,差异均具有统计学意义（P<0.05）。治疗后,两组患者Th17细胞频率、Th17/Treg细胞频率比值、IL-17水平均显著下降,而Treg细胞频率及TGF-β水平均显著升高（P<0.05）;与对照组相比,治疗后观察组Τh17细胞频率、Th17/Treg细胞频率比值、IL-17水平显著下降,而Treg细胞频率及TGF-β水平均显著升高（P<0.05）。对照组和观察组两组患者不良反应发生率分别为10.53%和14.04%,两组不良反应率相比较无显著差异。结论 参芪肝康片联合恩替卡韦治疗慢性乙型肝炎安全有效,能显著改善肝功能,并降低血清炎症因子水平,可能与影响Th17、Treg细胞频率及降低Th17/Treg细胞频率比值有关。     

玉屏风颗粒联合双嘧达莫治疗儿童过敏性紫癜的临床研究

目的 探讨玉屏风颗粒联合双嘧达莫片治疗儿童过敏性紫癜的临床疗效。方法 选取2020年1月-2022年10月在皖西卫生职业学院附属医院就诊的85例过敏性紫癜患儿,按照计算机随机排列法分为对照组(42例)和治疗组(43例)。对照组口服双嘧达莫片,3.0 mg/(kg·d),平均分3次服用。治疗组在对照组基础上温水冲服玉屏风颗粒,3~8岁,3次/d,半袋/次,8~12岁,3次/d,1袋/次。两组患儿连续治疗3个月。观察两组临床疗效,比较两组的主要症状消失时间、可溶性髓样细胞表达触发受体样转录因子1(TLT1)、白细胞介素(IL)-9、IL-21、辅助性T细胞(Th17)、调节性T细胞(Treg)、Th17/Treg水平。结果 治疗后,治疗组的总有效率95.35%较对照组的80.95%更高(P<0.05)。治疗后,治疗组患儿皮肤紫癫、腹痛、关节症状、肾脏症状消失时间均短于对照组(P<0.05)。治疗后,两组的血清TLT1、IL-9水平明显降低,血清IL-21水平明显升高(P<0.05);治疗后,治疗组的血清TLT1、IL-9水平低于对照组,血清IL-21水平高于对照组(P<0.05)。治疗后,两组的Th17、Th17/Treg水平低于治疗前,Treg水平高于治疗前(P<0.05);治疗后,治疗组的Th17、Th17/Treg水平低于对照组,Treg水平高于对照组(P<0.05)。结论 玉屏风颗粒联合双嘧达莫片可用于儿童过敏性紫癜,能够改善临床症状,减轻炎症反应,调节免疫功能平衡,且药物安全性良好。     

氨溴索联合甲泼尼龙治疗儿童哮喘急性发作的临床研究

目的 探讨氨溴索联合甲泼尼龙治疗儿童哮喘急性发作的临床效果。方法 选取2015年1月—2017年1月河南科技大学第一附属医院开元院区收治的哮喘急性发作患儿78例,随机分成对照组（39例）和治疗组（39例）。对照组静脉滴注注射用甲泼尼龙琥珀酸钠,1 mg/kg加入5%葡萄糖注射液100 mL,1次/d。治疗组在对照组治疗基础上静脉滴注盐酸氨溴索注射液,15 mg加入5%葡萄糖注射液100 mL,2次/d。两组均连续治疗7 d。观察两组患者临床疗效,同时比较治疗前后两组患者症状体征缓解时间、第1秒用力呼气容积占预计值百分比（FEV1%）、FEV1/用力肺活量（FVC）值、呼出气一氧化氮（FeNO）水平、儿童哮喘控制测试（C-ACT）评分、γ干扰素（IFN-γ）、白细胞介素-4（IL-4）和辅助性T细胞17（Th17）/调节性T细胞（Treg）比值。结果 治疗后,对照组的总有效率为79.5%,显著低于治疗组的94.9%,两组比较差异具有统计学意义（P<0.05）。治疗后,治疗组患儿喘息、咳嗽、气促、哮鸣音、湿罗音症状体征缓解时间比对照组显著缩短（P<0.05）。治疗后,两组FEV1%、FEV1/FVC值和C-ACT评分均明显增加（P<0.05）,FeNO水平显著下降（P<0.05）,且治疗后治疗组这些理化指标及C-ACT评分比对照组改善更明显（P<0.05）。治疗后,两组血清IFN-γ浓度显著升高（P<0.05）,血清IL-4水平及外周血Th17/Treg比率显著降低（P<0.05）,且治疗组IFN-γ、IL-4和Th17/Treg比对照组改善更明显（P<0.05）。结论 氨溴索联合甲泼尼龙治疗儿童哮喘急性发作疗效显著,可迅速减轻患儿症状,提高肺通气功能,改善气道炎症,缓解哮喘病情。     

舒芬太尼复合丙泊酚靶控输注对宫颈癌根治术患者Th17/Treg及氧化抗氧化系统的影响

目的 探讨舒芬太尼复合丙泊酚靶控输注对宫颈癌根治术患者T细胞 17(Th17)/调节性 T 细胞(Treg)及氧化抗氧化系统的影响。方法 选取2019年10月-2021 年 10 月延安市人民医院行宫颈癌根治术患者 80 例为研究对象,采用随机数字表法分为对照组和试验组,每组各 40 例,两组患者均行全身麻醉下腹腔镜宫颈癌根治术治疗,术中对照组行芬太尼复合丙泊酚靶控输注;试验组行舒芬太尼复合丙泊酚靶控输注。比较两组麻醉前 1 h、麻醉后 1 h、手术结束后 1 h 血清 Th17/Treg 相关指标(Th17、Treg、Th17/Treg)、氧化抗氧化系统相关指标[超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)]水平,分别于术毕、术后 6 h、术后 12 h 对两组患者进行疼痛程度评分(VAS 评分)。结果 麻醉后 1 h、手术结束后 1 h 两组血清 Treg 水平均较麻醉前 1 h 显著降低(P<0.05),麻醉后 1 h、手术结束后 1 h 两组血清 Th17、Th17/Treg水平均较麻醉前 1 h 显著升高(P<0.05);试验组麻醉后 1 h、手术结束后 1 h 血清 Treg 水平高于对照组,Th17、Th17/Treg水平低于对照组(P<0.05);麻醉后 1 h、手术结束后 1 h 两组 SOD、CAT、MDA 水平均较麻醉前 1 h 升高,差异有统计学意义(P<0.05);试验组麻醉后 1 h、手术结束后 1 h 血清 SOD、CAT 水平高于对照组,MDA 水平低于对照组(P<0.05);试验组术后 6、12 h VAS 评分均显著低于对照组(P<0.05)。结论 与芬太尼复合丙泊酚靶控输注比较,宫颈癌患者根治术中采用舒芬太尼复合丙泊酚靶控输注能降低手术及麻醉对患者 Th17/Treg 及氧化抗氧化系统的影响,改善镇痛效果。     

樟芝多糖通过CD4+CD25+Foxp3+调节性T细胞对小鼠非酒精性脂肪性肝病的保护作用

目的 研究樟芝多糖通过CD4⁺CD25⁺Foxp3⁺调节性T细胞（Treg）的调控对小鼠非酒精性脂肪性肝病（NAFLD）的保护作用。方法 高脂饮食构建小鼠NAFLD模型,设置对照组、模型组、低剂量组、高剂量组。樟芝多糖干预1~4周中每周流式细胞术检测外周血Treg细胞的比例,谷丙转氨酶（ALT）、谷草转氨酶（AST）的表达,外周血中转化生长因子β（TGF-β）、白介素-6（IL-6）的表达。樟芝多糖干预4周后,小鼠处死,取肝脏进行油红染色,Western blot法检测肝组织中TGF-β和Foxp3、Smad3蛋白的表达,RT-qPCR检测IL-6、TGF-β、Foxp3、Smad3的mRNA表达。结果 高脂饮食喂养4周后成功构建NAFLD小鼠模型,且模型组中Terg比例显著低于对照组（P<0.05）,樟芝多糖干预后Treg比例相比模型组显著增高（P<0.05）,小鼠肝功能得到显著改善,外周血中TGF-β表达上调、IL-6的表达下调,肝组织中TGF-β和Foxp3、Smad3蛋白和mRNA均上调,而IL-6的mRNA表达下调。结论 樟芝多糖可以通过Treg和TGF-β-Smad3信号对NAFLD起到保护作用,作用机制和免疫改善有关。     

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.     

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.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.