疏风解毒胶囊免疫调节作用机制研究

目的 探讨疏风解毒胶囊免疫调节作用机制。方法 采用肺炎链球菌致肺炎大鼠模型,观察疏风解毒胶囊给药后对淋巴细胞分类,细胞因子白细胞介素-1α（IL-1α）、IL-1β、IL-2、IL-4、IL-6、IL-10、肿瘤坏死因子-α（TNF-α）、α干扰素（IFN-α）、γ干扰素（IFN-γ）水平,免疫球蛋白A（IgA）、免疫球蛋白M（IgM）、免疫球蛋白G（IgG）水平,胸腺、脾脏、肺脏质量的影响。结果 疏风解毒胶囊能显著降低模型大鼠外周血B淋巴细胞比例、CD8⁺比例,降低血清IL-1α、IL-1β、IL-2、IL-10、TNF-α、IFN-α、IFN-γ、IgM、IgG水平,降低肺炎大鼠胸腺、脾脏、肺脏质量,升高外周血CD4⁺/CD8⁺及NK细胞比例。结论 疏风解毒胶囊有显著的免疫调节作用,其通过降低B淋巴细胞、CD8⁺比例及IL-1α、IL-1β、IL-2、IL-10、TNF-α、IFN-α、IFN-γ、IgM、IgG水平,降低肺炎大鼠胸腺、脾脏、肺脏质量,升高CD4⁺/CD8⁺及NK细胞比例对肺炎模型大鼠有显著的治疗作用。     

米诺环素治疗慢性牙周炎的临床疗效及其对外周血T细胞亚群、PD-1、PD-L1表达的影响

目的 探究米诺环素治疗慢性牙周炎的临床疗效及其对外周血T细胞亚群及程序性死亡分子-1（PD-1）、程序性死亡分子-1配体（PD-L1）表达的影响。方法 选择2015年1月-2017年1月在榆林市星元医院口腔科接受治疗的96例慢性牙周炎患者为研究对象。根据随机数字表法将患者分为对照组和观察组,每组各48例。对照组患者采用龈下刮治及根面平整进行治疗。观察组患者在对照组治疗的基础上在牙周袋底部缓慢注入盐酸米诺环素软膏,0.2 g/次,1次/周,边注射边后退。两组均治疗4周。观察两组患者的临床疗效,同时比较两组治疗前后的牙龈指数（GI）、菌斑指数（PLI）、牙槽骨吸收、附着丧失（CAL）以及牙周袋深度（PD）、C反应蛋白（CRP）、白细胞介素-10（IL-10）、龈沟出血指数（SBI）、外周血T淋巴细胞亚群和表面PD-1、PD-L1的表达情况。结果 治疗后,对照组患者临床总有效率为72.92%,显著低于观察组的91.67%（P<0.05）。治疗后,两组患者GI、PLI、PD、CAL和牙槽骨吸收等指标均显著降低（P<0.05）;且观察组以上各指标均显著低于对照组（P<0.05）。治疗后,两组患者龈沟液中CRP水平和SBI评分均显著降低,而龈沟液中IL-10水平显著升高（P<0.05）;且观察组龈沟液中CRP、IL-10水平和龈沟出血指数均优于对照组（P<0.05）。治疗后,两组患者外周血T淋巴细胞亚群中CD4⁺和CD4⁺/CD8⁺均显著降低,CD8⁺显著升高（P<0.05）;且观察组外周血T淋巴细胞亚群中CD4⁺和CD4⁺/CD8⁺均显著低于对照组,CD8⁺比例高于对照组（P<0.05）。治疗后,两组患者外周血CD4⁺和CD8⁺T淋巴细胞表面的PD-1和PD-L1表达水平均显著降低（P<0.05）;且观察组外周血CD4⁺和CD8⁺T淋巴细胞表面的PD-1和PD-L1表达水平均显著低于对照组（P<0.05）。结论 米诺环素治疗慢性牙周炎可有效改善患者各项牙周指标,改善牙周组织炎症反应抑制作用,在慢性牙周炎临床治疗中具有重要价值。     

土茯苓对环孢素A诱导的免疫抑制小鼠免疫功能的影响

目的 探讨土茯苓水提液对环孢素A诱导的免疫抑制小鼠免疫功能的影响。方法 小鼠腹腔注射环孢素A 5 d致免疫抑制模型,造模成功后随机分为模型组、左旋咪唑组（3.79 g·kg^-1,阳性药）和土茯苓低、中、高剂量组（4.55,9.1,13.65 g·kg^-1）（n=16）,连续给药治疗5 d后,处死小鼠,取脾、胸腺,称重计算脾指数和胸腺指数,流式细胞术检测CD3⁺CD4⁺,CD3⁺CD8⁺;酶联免疫吸附法检测IL-2,IL-6,IFN-γ。结果 造模后小鼠脾指数显著高于正常对照组（P<0.05）,胸腺指数明显降低,脾T细胞CD3⁺CD4⁺显著降低（P<0.05）;与模型组比较,各治疗组小鼠脾指数均有不同程度降低,土茯苓水提液中剂量组差异显著（P<0.05）,但胸腺指数无显著变化;左旋咪唑组、土茯苓中、高剂量组脾T细胞CD3⁺CD4⁺数目显著增加（P<0.01）,各治疗组脾脏IFN-γ均显著下降（P<0.05）。结论 土茯苓水提液能通过降低脾指数、增加脾T细胞CD3⁺CD4⁺的数目,增强机体免疫功能,并下调脾脏内较高的IFN-γ,其调节机制可能与左旋咪唑类似。     

2型糖尿病合并尿路感染老年患者细胞免疫功能的研究

目的 探讨2型糖尿病合并尿路感染老年患者细胞免疫功能。方法 收集2016年6月至2017年8月合肥市滨湖医院确诊的2型糖尿病老年患者87例，分为试验组（糖尿病合并尿路感染，n=42）和糖尿病对照组（糖尿病无感染，n=45），另以同期收集的33例非糖尿病尿路感染患者作为感染对照组，观察并比较各组患者炎性分子水平、T淋巴细胞亚群水平、辅助性T细胞亚群的水平。结果 3组患者炎性分子水平、T淋巴细胞亚群水平、辅助性T细胞亚群的水平差异有统计学意义（P < 0.05），其中试验组外周血白细胞介素-6（IL-6）、IL-10、IL-17、C-反应蛋白水平（CRP）高于糖尿病对照组和感染对照组，IL-17/IL-10比例低于糖尿病对照组和感染对照组，差异均有统计学意义（P < 0.05），糖尿病对照组IL-6、CRP水平低于感染对照组，差异有统计学意义（P < 0.05）；试验组外周血CD3⁺CD4⁺T细胞百分比高于糖尿病对照组和感染对照组，CD3⁺CD8⁺T细胞百分比低于糖尿病对照组和感染对照组，差异均有统计学意义（P < 0.05），糖尿病对照组外周血CD3⁺CD4⁺T细胞百分比、CD3⁺CD8⁺T细胞百分比和感染对照组相比差异无统计学意义（P > 0.05）；试验组外周血调节性T细胞（Treg）和Th17百分比高于糖尿病对照组和感染对照组，但Th17/Treg比例低于糖尿病对照组和感染对照组，差异均有统计学意义（P < 0.05），糖尿病对照组Treg百分比、Th17百分比及Th17/Treg比例与感染对照组比较，差异无统计学意义（P > 0.05）。结论 2型糖尿病合并尿路感染老年患者存在CD3⁺CD4⁺T细胞水平下调和CD3⁺CD8⁺T细胞水平上调，也存在Treg/Th17功能失衡。     

CD4+CD25+调节性T淋巴细胞在儿童传染性单核细胞增多症的变化及作用

目的 观察儿童传染性单核细胞增多症（IM）治疗前后外周血T淋巴细胞亚群和CD4⁺CD25⁺调节性T淋巴细胞（Treg细胞）比例变化,分析Treg对IM的影响。方法 选取2017年1月至2018年5月安徽医科大学第二附属医院儿科收治的IM患儿60例作为观察组,以同期于本院儿童保健门诊行体检的40例健康儿童作为对照组,采用流式细胞术检测观察组治疗前、后及对照组的外周血T细胞亚群（CD3⁺T细胞、CD3⁺CD4⁺T细胞、CD3⁺CD8⁺T细胞比例,CD4/CD8比值）、CD4⁺CD25⁺调节性T淋巴细胞比例,对比分析两组患者机体细胞免疫功能的变化。结果 观察组治疗前CD3⁺T细胞比例、CD3⁺CD8⁺T细胞比例显著高于对照组;CD3⁺CD4⁺T细胞比例、CD4/CD8比值低于对照组,差异均有统计学意义（P <0.05）。观察组治疗后CD3⁺T细胞比例、CD3⁺CD8⁺T细胞比例均低于观察组治疗前;CD3⁺CD4⁺T细胞比例、CD4/CD8比值高于治疗前,差异均有统计学意义（P <0.05）。观察组治疗前外周血Treg细胞比例低于正常对照组,差异有统计学意义（P <0.05）;而观察组治疗后外周血Treg细胞比例高于治疗前,差异有统计学意义（P <0.05）。结论 IM患儿存在T细胞亚群比例的变化,Treg细胞水平的降低,可能参与IM患儿疾病的发生发展过程。     

连花清瘟颗粒联合奥司他韦治疗流行性感冒(风热犯卫证)的疗效及对免疫功能的影响

目的 探讨连花清瘟颗粒联合磷酸奥司他韦治疗流行性感冒 （风热犯卫证） 的疗效及对患者免疫功能的影响。方法 前瞻性选取 2019年 1月—2020年 5月南通市中医院收治的 140例流行性感冒 （风热犯卫证） 患者,采用随机对照非盲法将其分为对照组与试验组,每组各70例。两组患者予以对症治疗,对照组在对症基础上采用磷酸奥司他韦胶囊治疗,每次75 mg,每天2次,分别于早晚餐后30 min口服。试验组在对照组基础上加用连花清瘟颗粒治疗,每次1袋,每天3次,餐后30 min口服。两组患者均连续治疗5 d。评估两组临床疗效及不良反应。比较两组治疗前后中医证候积分、γ-干扰素（IFN-γ）、白细胞介素-6（IL-6）以及T淋巴细胞亚型水平。结果 试验组总有效率较对照组显著升高（P＜0.05）。两组患者治疗后中医证候积分及IFN-γ、IL-6、CD8⁺水平均较同组治疗前显著降低（P＜0.05）,试验组患者治疗后中医证候积分及 IFN-γ、IL-6、CD8⁺水平均较对照组显著降低（P＜0.05）。两组患者治疗后 CD3⁺、CD4⁺及 CD4⁺/CD8⁺水平均较同组治疗前显著升高（P＜0.05）,试验组患者治疗后 CD3⁺、CD4⁺及 CD4⁺/CD8⁺水平均较对照组显著升高（P＜0.05）。两组均未发生不良反应。结论 连花清瘟颗粒联合磷酸奥司他韦胶囊治疗流行性感冒（风热犯卫证）的疗效及安全性较高,其不仅能减轻患者中医临床症状,同时还能调节患者免疫功能,促进患者早日康复。     

奥司他韦联合热毒宁治疗儿童流行性感冒的疗效及其对免疫功能的影响

目的 探讨奥司他韦联合热毒宁治疗儿童流行性感冒的疗效及其对免疫功能的影响。方法 选择2017年10月至2018年9月南阳市中心医院收治的112例流行性感冒患儿为研究对象,按照随机数字表法分为观察组和对照组,各56例。对照组患儿给予热毒宁注射液静滴治疗,观察组在对照组基础上给予奥司他韦颗粒口服,均连续治疗3天。比较两组患儿的治疗总有效率;观察两组患儿临床症状改善时间、血清白细胞介素6（IL-6）、C-反应蛋白（CRP）、γ-干扰素（IFN-γ）水平及T淋巴细胞亚群（CD3⁺、CD4⁺、CD8⁺）水平,并计算CD4⁺/CD8⁺值。结果 治疗3天后,观察组治疗总有效率（96.43%）高于对照组（83.93%）,差异有统计学意义（P<0.05）;观察组发热、鼻塞、流涕、咳嗽等症状恢复时间均短于对照组,差异有统计学意义（P<0.01）;观察组IL-6、CRP、IFN-γ水平治疗前后差值高于对照组,差异有统计学意义（P<0.05）;观察组CD3⁺、CD4⁺、CD4⁺/CD8⁺治疗前后差值高于对照组,CD8⁺治疗前后差值低于对照组,差异均有统计学意义（P<0.05）。结论 奥司他韦联合热毒宁治疗儿童流行性感冒可有效提高临床疗效,改善患儿免疫功能。     

含阿莫西林克拉维酸钾的铋剂四联方案治疗幽门螺杆菌感染致慢性胃炎的有效性及安全性观察

目的 探讨含阿莫西林克拉维酸钾的铋剂四联方案治疗幽门螺杆菌感染致慢性胃炎的临床疗效。方法 选取2020年5月—2021年8月在北京市海淀医院消化内科接受治疗的116例幽门螺杆菌感染致慢性胃炎患者为研究对象,按照治疗方案不同将患者分为对照组和试验组,每组58例,对照组给予含阿莫西林的铋剂四联方案治疗,试验组给予含阿莫西林克拉维酸钾的铋剂四联方案治疗,两组均治疗14 d。分别于治疗前后采用酶联免疫吸附（ELISA）法检测血清炎症因子白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）、胃动素（MTL）、胃泌素（GAS）水平;分别于治疗前后采用流式细胞仪检测T淋巴细胞亚群（CD4⁺、CD8⁺、CD4⁺/CD8⁺）水平的变化;记录两组治疗总有效率和不良反应发生率。结果 治疗后,对照组和试验组患者血清IL-6、TNF-α、CRP、GAS、CD8⁺水平较本组治疗前均显著降低（P＜0.05）,而MTL、CD4⁺、CD4⁺/CD8⁺水平较本组治疗前均显著升高（P＜0.05）,且治疗后试验组血清IL-6、TNF-α、CRP、GAS、CD8⁺水平显著低于对照组（P＜0.05）,MTL、CD4⁺、CD4⁺/CD8⁺水平显著高于对照组（P＜0.05）。试验组的总有效率为93.10%,显著高于对照组的79.31%（P＜0.05）,试验组的不良反应发生率为6.90%,显著低于对照组的12.07%（P＜0.05）。结论 含阿莫西林克拉维酸钾的铋剂四联方案治疗幽门螺杆菌感染致慢性胃炎疗效更为显著,能抑制机体内炎症反应、调控胃肠道激素分泌,提高患者免疫力,多途径共同作用促进患者病情好转,值得临床推广使用。     

藏药青叶胆对实验性慢性肝损伤小鼠T淋巴细胞亚群的影响

目的 观察青叶胆对小鼠慢性肝损伤的保护作用及其对小鼠脾脏T淋巴细胞亚群的调节作用。方法 采用腹腔注射四氯化碳（CCl₄）造成小鼠化学性肝损伤模型,检测小鼠血清天冬氨酸转氨酶（aspartate aminotransferase,AST）、丙氨酸转氨酶（alanine aminotransferase,ALT）、总蛋白（total protein,TP）及总胆红素（total bilirubin,TBI）;HE染色,观察肝组织形态;流式细胞术检测CD3⁺、CD4⁺及CD8⁺阳性细胞数的变化情况,计算CD4⁺/CD8⁺比例,并与模型组和对照组比较。结果 青叶胆对CCl₄造成的小鼠慢性肝脏损伤具有保护作用,与模型组相比,能明显降低小鼠血清ALT、AST含量（P<0.01）,升高TP含量（P<0.01）;与模型组相比,青叶胆低剂量组对CD3⁺细胞具有下调作用（P<0.05）,对CD8⁺细胞的上调作用和对CD4⁺/CD8⁺比值的下调作用具有显著性差异（P<0.01）;高剂量组对CD8⁺细胞的上调作用和对CD4⁺/CD8⁺比值的下调作用具有统计学意义（P<0.05）。结论 青叶胆对CCl₄诱导的小鼠慢性肝损伤具有保护作用,其机制可能是通过调节T淋巴细胞亚群,提高免疫功能。     

2HPAZV/7~10DZV化疗方案联合经支气管镜局部注射与单纯化疗对耐多药肺结核的治疗效果比较

目的 比较分析化疗联合经支气管镜局部药物注射与单纯化疗对耐多药肺结核的治疗效果。方法 选择2014年1月-2016年12月铜川市人民医院的95例耐多药肺结核患者,随机分为两组。对照组给予2HPAZV/7~10DZV化疗方案,观察组在对照组基础上联合经支气管镜局部注入左氧氟沙星0.2 g,丁胺卡那0.2 g,异烟肼0.2 g。每周治疗1次,共治疗2个月。比较两组的痰菌涂片阴转率、免疫功能、血清白介素-4（IL-4）、干扰素-γ（INF-γ）水平和症状的消失率。结果 治疗后观察组的痰菌涂片阴转率明显高于对照组,差异有统计学意义（P<0.05）。两组治疗后的CD4⁺/CD8⁺以及CD4⁺均明显升高,CD8⁺明显降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组明显优于对照组,差异有统计学意义（P<0.05）。两组治疗后的血清IL-4水平明显降低、INF-γ水平明显升高,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组的血清IL-4、INF-γ水平明显优于对照组,差异有统计学意义（P<0.05）。观察组的咳嗽、发热、咳痰、呼吸困难和胸痛等症状的消失率明显高于对照组,差异有统计学意义（P<0.05）。结论 化疗联合经支气管镜局部注射对耐多药肺结核的治疗效果显著优于单纯化疗,不仅有助于患者症状的消失,还能改善患者的免疫状态,降低炎性因子水平。     

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.     

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.     

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.