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。     

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。     

甲氨蝶呤联合麝香乌龙丸对寒湿痹阻型类风湿关节炎患者的疗效及对炎症因子的影响

目的 研究麝香乌龙丸联合甲氨蝶呤对寒湿痹阻型类风湿关节炎患者白介素-1（IL-1）、白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）的影响。方法 选择2015年2月-2018年1月铜川市人民医院收治的寒湿痹阻型类风湿关节炎患者103例,按入院顺序随机将其分为两组。对照组口服麝香乌龙丸,每次3 g,每日2次;观察组在对照组基础上联合甲氨蝶呤片,每次7.5 mg,每日1次。两组均治疗60 d。比较两组患者的疗效、中医证候积分、疼痛评分及治疗前后IL-1、IL-6、TNF-α含量的变化情况。结果 观察组的有效率96.08%明显高于对照组78.85%,差异有统计学意义（P<0.05）。治疗后,两组的中医证候积分、疼痛评分均比治疗前显著降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组明显低于对照组,差异有统计学意义（P<0.05）。与治疗前比较,两组患者治疗后IL-1、IL-6、TNF-α含量均显著下降（P<0.05）;治疗后两组患者相比,观察组IL-1、IL-6、TNF-α含量均显著低于对照组（P<0.05）。结论 麝香乌龙丸联合甲氨蝶呤治疗寒湿痹阻型类风湿关节炎患者的疗效显著,且该方法能够显著改善患者的IL-1、IL-6、TNF-α水平,临床应用效果显著。     

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。     

托珠单抗对类风湿关节炎患者疗效、免疫球蛋白及辅助性T细胞水平的影响

目的 观察托珠单抗对类风湿关节炎（RA）患者的疗效,以及对患者免疫球蛋白、辅助性T细胞水平的影响。方法 选择本院收治的RA患者90例,随机分为对照组与观察组,每组45例。对照组患者接受英夫利西单抗联合甲氨蝶呤治疗方案,观察组患者接受托珠单抗联合甲氨蝶呤治疗方案。两组患者均连续治疗6个月。比较两组患者治疗后的临床疗效;分别检测两组患者治疗前后血清中免疫球蛋白、T辅助细胞-1（T helper1,Th1）以及调节性T细胞（T Regulatory,Treg）的水平。结果 治疗后,两组患者晨僵、关节压痛及关节肿胀情况均有所好转,且观察组患者的上述症状情况好转程度明显优于对照组（P<0.05）。两组患者血清中IgG及Th1细胞水平均显著降低,且观察组患者血清中2种细胞水平显著低于对照组（P<0.05）;而两组患者Treg细胞水平均有明显升高,且观察组Treg水平显著高于对照组（P<0.05）。结论 托珠单抗可有效改善RA患者临床症状,改善患者免疫功能紊乱,具有较好的临床疗效。     

七味通痹口服液联合甲氨蝶呤治疗类风湿关节炎的疗效观察及其对血清疼痛介质和炎症因子的影响

目的 探讨七味通痹口服液联合甲氨蝶呤治疗类风湿关节炎的疗效观察及其对血清疼痛介质和炎症因子的影响。方法 选取2019年5月—2020年11月海南省中医院收治的84例类风湿关节炎患者作为研究对象，按照治疗方法将84例患者分为对照组和观察组，每组各42例。对照组口服甲氨蝶呤片，10 mg/次，1次/周。观察组在对照组基础上口服七味通痹口服液，10 mL/次，3次/d。两组连续治疗3个月。观察两组患者的临床疗效，比较两组治疗前后的关节压痛数、肿胀数、晨僵持续时间，同时比较两组视觉模拟评分法（VAS）、血清前列腺素E₂（PGE₂）、血浆P物质（SP）、白细胞介素-17（IL-17）、抗链球菌溶血素O（ASO）、类风湿因子（RF）、C反应蛋白（CRP）和血沉（ESR）水平。结果 治疗后，观察组总有效率为85.71%，显著高于对照组的66.67%，两组间对比差异有统计学意义（P<0.05）。两组治疗后的压痛数、肿胀数、晨僵持续时间、疼痛程度评分显著降低（P<0.05）；治疗后，观察组的压痛数、肿胀数、晨僵持续时间、疼痛程度评分显著低于对照组，差异有统计学意义（P<0.05）。两组治疗后的PGE₂、SP、IL-17水平显著降低（P<0.05）；治疗后，观察组的PGE₂、SP、IL-17水平显著低于对照组，差异有统计学意义（P<0.05）。两组治疗后的ASO、RF、CRP、ESR水平显著降低（P<0.05）；治疗后，观察组的ASO、RF、CRP、ESR水平显著低于对照组，差异有统计学意义（P<0.05）。结论 七味通痹口服液联合甲氨蝶呤可提高类风湿关节炎的疗效，降低患者血清疼痛介质和炎症因子的水平，进一步减轻临床症状体征，具有一定临床研究价值。     

宣肺止嗽合剂联合沙美特罗替卡松治疗咳嗽变异性哮喘的临床研究

目的 探讨宣肺止嗽合剂联合吸入沙美特罗替卡松治疗咳嗽性变异性哮喘的临床疗效。方法 选取2019年1月—2019年12月在天津市泰达医院治疗的哮喘患者282例,随机分为对照组（141例）和治疗组（141例）。对照组吸入沙美特罗替卡松吸入粉雾剂,50 μg/次,2次/d。治疗组在对照组基础上口服宣肺止嗽合剂,20 mL/次,3次/d。两组连用7 d。观察两组患者临床疗效,同时比较治疗前后两组患者第1秒用力呼气量（FEV1）、第1秒用力呼气容积占预计百分比（FEV1% pred）和FEV1/最大呼吸量（FVC）,外周血调节性T细胞（Treg）、辅助性T细胞17（Th17）百分比和Treg/Th17,ACT评分和mMRC评分,及呼出气一氧化氮（FeNO）和嗜酸性粒细胞计数。结果 治疗后,对照组临床有效率为74.47%,显著低于治疗组的95.74%,两组比较差异具有统计学意义（P<0.05）。治疗后,两组FEV1、FEV1% pred和FEV1/FVC明显增加（P<0.05）,且治疗组较对照组显著上升（P<0.05）。治疗后,两组Treg细胞百分比显著升高（P<0.05）,Th17百分比及Treg/Th17比值明显降低（P<0.05）,且治疗组Treg细胞百分比、Th17百分比和Treg/Th17比值明显好于对照组（P<0.05）。治疗后,两组患者ACT评分显著升高（P<0.05）,mMRC评分明显降低（P<0.05）,且治疗组ACT评分和mMRC评分明显好于同期对照组（P<0.05）。治疗后,两组FeNO和嗜酸性粒细胞计数显著降低（P<0.05）,且治疗组FeNO和嗜酸性粒细胞计数较对照组明显下降（P<0.05）。结论 宣肺止嗽合剂联合沙美特罗替卡松治疗咳嗽变异性哮喘疗效显著,能够有效的改善肺部功能,调节免疫能力,降低FeNO和炎症水平。     

艾拉莫德联合甲氨蝶呤治疗类风湿性关节炎临床研究

目的 研究艾拉莫德联合甲氨蝶呤治疗类风湿性关节炎临床效果。方法 选择2015年1月-2017年11月在揭阳市人民医院进行诊治的60例类风湿性关节炎患者,随机分为两组。对照组口服甲氨蝶呤治疗,每次10 mg,每天1次;观察组联合口服艾拉莫德治疗,每次25 mg,每天2次。两组均治疗3个月。比较两组的临床治疗效果,并比较两组治疗前后的血清C反应蛋白、类风湿因子、抗环瓜氨酸肽抗体和红细胞沉降率,以及白介素-6、淋巴细胞绝对值、免疫球蛋白G。结果 观察组的有效率90.00%高于对照组70.00%,差异有统计学意义（P<0.05）。治疗后两组的血清C反应蛋白、类风湿因子、抗环瓜氨酸肽抗体和红细胞沉降率均明显降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组明显低于对照组,组间差异有统计学意义（P<0.05）。治疗后两组的淋巴细胞绝对值、免疫球蛋白G、白介素-6均明显降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组明显低于对照组,组间差异有统计学意义（P<0.05）。两组的不良反应率相比无明显差异。结论 艾拉莫德联合甲氨蝶呤治疗类风湿性关节炎临床效果显著,是一种安全有效的治疗方案。     

桐油联合阿维A酸对银屑病的疗效及其对IL-23/Th17信号通路的影响

目的 观察桐油联合阿维A酸对轻、中度寻常型银屑病的疗效及其对IL-23/Th17信号通路的影响。方法 将196例寻常型银屑病患者随机分为桐油组及对照组,每组98例,对照组患者均给予阿维A酸联合窄谱中波紫外线（NB-UVB）治疗,桐油组患者在对照组治疗基础上给予桐油外敷。以银屑病皮损面积和严重程度指数（psoriasis area and severity index,PASI）评价桐油组及对照组疗效。酶联免疫吸附试验法（ELISA）检测治疗前后2组皮损组织中IL-17、IL-22、TNF-α和IL-23水平变化。免疫组织化学法分析治疗前后2组皮损组织中Th17细胞含量变化。结果 桐油组的总有效率（94.90%）显著高于对照组（76.53%）（P<0.05）。与治疗前相比,治疗后2组PASI评分均显著降低（P<0.01）,且治疗后桐油组显著低于对照组（P<0.05）。与治疗前相比,治疗后2组皮损中IL-23、IL-17、IL-22和TNF-α水平均显著降低（P<0.05）,且治疗后桐油组显著低于对照组（P<0.05）。治疗后2组患者皮损组织中Th17细胞百分比显著低于治疗前,且桐油组显著低于对照组（P<0.05）。桐油组不良反应发生率（14.29%）略高低于对照组（10.20%）,但差异不具有统计学意义。结论 桐油外敷联合阿维A酸治疗轻、中度寻常型银屑病有较好的疗效,其机制可能与抑制患者皮损组织中IL-23/Th17信号通路的活性有关。     

金骨莲胶囊联合右旋酮洛芬氨丁三醇治疗风湿痹阻型类风湿关节炎的临床研究

目的 探讨金骨莲胶囊联合右旋酮洛芬氨丁三醇片治疗风湿痹阻型类风湿关节炎的疗效。方法 选取2022年1月—2022年12月山西医科大学附属运城市中心医院收治的类风湿关节炎患者100例,根据治疗方案不同将患者分为对照组（50例）和治疗组（50例）。对照组患者口服右旋酮洛芬氨丁三醇片,12.5 mg/次,3次/d。治疗组在对照组基础上口服金骨莲胶囊,5粒/次,3次/d。两组患者均持续治疗4周。观察两组患者临床疗效,比较治疗前后两组患者中医证候积分、肿胀关节数、压痛关节数,及红细胞沉降率（ESR）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平。结果 治疗后,治疗组总有效率显著优于对照组（98.00% vs 86.00%,P＜0.05）。治疗后,两组患者中医证候积分、肿胀关节数、压痛关节数及ESR、TNF-α、IL-6水平比治疗前显著降低（P＜0.05）,且治疗组明显低于对照组（P＜0.05）。结论 金骨莲胶囊联合右旋酮洛芬氨丁三醇片治疗风湿痹阻型类风湿关节炎疗效及安全性均较高,能有效降低患者炎性水平,减轻关节疼痛及改善中医证候。     

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.