芪防鼻敏颗粒对变应性鼻炎大鼠炎性因子表达的影响研究

摘 要 目的：观察芪防鼻敏颗粒对变应性鼻炎（AR）大鼠血清白介素 4(IL 4),白介素 17(IL 17）,肿瘤坏死因子（TNF α）及鼻黏膜γ干扰素（IFN γ）、白介素 6（IL 6）、TNF α表达的影响。方法: SD大鼠随机分为正常组,模型组,氯雷他定组（1.17 mg·kg^-1）,鼻炎康组（0.6 g·kg^-1）,芪防鼻敏颗粒高（26.48 g·kg^-1）、中（13.24 g·kg^-1）、低（6.62 g·kg^-1）剂量组。采用卵蛋白（OVA）建立AR大鼠模型。造模成功后分别灌胃给药,连续14 d。酶联免疫吸附法（ELISA）检测AR大鼠血清IL 4、IL 17、TNF α水平,免疫组化染色法（IHC）检测鼻黏膜IFN γ、IL 6、TNF α表达。结果:与正常组相比,模型组大鼠血清IL 4、IL 17水平明显上升（P<0.01）;鼻黏膜IFN γ阳性表达明显降低（P<0.05）,IL 6、TNF α阳性表达显著升高（P<0.01）。与模型组相比,氯雷他定组、芪防鼻敏颗粒中剂量组大鼠血清IL 4水平显著下降（P<0.05）,芪防鼻敏颗粒低剂量组大鼠血清IL 17水平明显下降（P<0.05）,氯雷他定组、鼻炎康组、芪防鼻敏颗粒高、中剂量组大鼠血清TNF α水平显著下降（P<0.05或P<0.01）;高、低剂量组大鼠鼻黏膜IFN γ阳性表达显著升高（P<0.05或P<0.01）,高、中剂量组IL 6阳性表达显著降低（P<0.01）,高剂量组TNF α阳性表达显著降低（P<0.01）。与氯雷他定组相比,鼻炎康组、芪防鼻敏颗粒高剂量组大鼠血清IL 17水平明显上升（P<0.05）,鼻炎康组、芪防鼻敏颗粒低剂量组大鼠血清IL 4水平明显上升（P<0.05）,芪防鼻敏颗粒高、中、低剂量组TNF α阳性表达显著升高（P<0.05）;与鼻炎康组比较,芪防鼻敏颗粒中剂量组大鼠血清IL 4水平明显下降（P<0.05）;与芪防鼻敏颗粒低剂量组相比,芪防鼻敏颗粒高剂量组大鼠血清IL 17水平明显上升（P<0.05）,芪防鼻敏颗粒中剂量组大鼠血清IL 4水平明显下降（P<0.05）。结论:芪防鼻敏颗粒可增加AR鼻黏膜IFN γ表达,降低血清IL 4、TNF α、IL 17水平及鼻黏膜TNF α、IL 6表达。     

恩替卡韦联合苦参素治疗慢性乙型肝炎疗效及对患者外周血免疫球蛋白、TNF-α和IL-6的影响

摘 要 目的：观察恩替卡韦联合苦参素治疗慢性乙型肝炎的疗效,及对患者外周血免疫球蛋白、肿瘤坏死因子 α（TNF α）和白细胞介素6（IL 6）水平的影响。方法：采用随机双盲对照试验方法,70例慢性乙型肝炎患者随机分为观察组35与对照组各35例。对照组给予恩替卡韦分散片0.5 mg,po,qd;观察组在此基础上加用苦参素胶囊0.2 g,po,tid。两组疗程均为12个月。观察并记录两组患者治疗前后血清HBV DNA及ALT水平、外周血免疫球蛋白（IgM、IgA、IgG）及血清TNF α、IL 6水平变化,比较两组治疗后ALT复常率、HBV DNA阴转率、HBeAg/HBeAb转换率、HBeAg阴转率。结果：治疗后,两组患者ALT水平均较治疗前明显下降（P<0.01）,但两组间比较差异无统计学意义（P>0.05）;两组患者HBV DNA水平也较治疗前明显下降（P<0.01）,且观察组明显低于对照组（P<0.01）。观察组ALT复常率、HBV DNA阴转率、HBeAg/HBeAb转换率、HBeAg阴转率均显著低于对照组（P<0.05）。治疗后,观察组外周血IgM、IgA、IgG含量,以及血清TNF α、IL 6水平较治疗前显著增加（P<0.01或P<0.05）,且均明显高于对照组（P<0.05）。结论：恩替卡韦联合苦参素抗HBV疗效显著,并且能显著提高外周血免疫球蛋白含量,增强免疫应答水平、降低血清TNF α、IL 6含量,控制肝内炎症发展,值得在临床应用中推广。     

百令胶囊辅助治疗哮喘慢性阻塞性肺疾病重叠患者疗效观察

摘 要 目的：观察百令胶囊辅助治疗哮喘 慢性阻塞性肺疾病重叠（ACO）患者的临床疗效。方法：61例ACO门诊患者随机分为对照组30例和观察组31例。对照组给予常规治疗;观察组在对照组治疗基础上加用百令胶囊,比较两组患者随访1年后的急性加重次数及稳定期持续时间,以及治疗前后两组肺功能（FEV1% pred、FEV1/FVC、PEF日变异率）、诱导痰炎细胞分类和比例、血清炎症因子（IL 4、IL 6、TNF α）水平、SGRQ评分和6 min步行距离（6 MWD）等指标等变化。 结果：观察组随访1年后急性加重次数明显低于对照组,稳定期持续时间明显高于对照组（P<0.05）。观察组治疗后PEF日变异率较前降低（P<0.05）。治疗后两组诱导痰中性粒细胞和嗜酸性粒细胞比例降低,巨噬细胞比例升高（P<0.01）,且观察组中性粒细胞和嗜酸性粒细胞比例低于对照组,巨噬细胞比例高于对照组（P<0.05）。两组治疗后血IL 4、IL 6、TNF α均较治疗前下降（P＜0.05）,SGRQ评分降低,6MWD值升高（P＜0.05）;两组间比较差异无统计学意义（P>0.05）。结论：百令胶囊用于辅助治疗ACO可以改善患者的临床指标,提高生活质量。     

丹参多酚酸盐联合常规治疗急性脑梗死疗效及对血清白细胞介素-6影响观察

摘 要 目的：观察丹参多酚酸盐联合常规治疗对急性脑梗死患者的疗效及对血清炎性因子白细胞介素 6（IL 6）的影响。方法: 70例急性脑梗死患者随机分为观察组和对照组各35例,均给予脑梗死常规治疗,观察组在此基础上加用丹参多酚酸盐注射液200 mg+0.9%氯化钠注射液250 ml,ivd,qd。两组疗程均为2周。另选取30例健康体检者为健康对照组。分别于治疗第3天、第7天、第10天及第14天评定两组患者神经功能缺损评分（NIHSS评分）;于发病24 h内,治疗第3天、第7天、第10天及第14天检测两组患者血清IL 6水平,并与健康对照组的血清IL 6水平相比较。结果: 治疗第7天开始观察组NIHSS评分较入院时显著下降（P<0.05）,此后NIHSS评分持续下降;对照组NIHSS评分则在治疗第10天开始显著下降（P<0.05）。治疗第7天后,观察组NIHSS评分均显著低于对照组同期（P<0.05）。两组入院24 h内血清IL 6水平均显著高于健康对照组（P<0.05）。观察组血清IL 6水平从治疗第7天开始逐渐下降,治疗第14天时与健康对照组差异无统计学意义(P>0.05)。对照组血清IL 6水平在治疗第10天后逐渐下降,但对照组各时段血清IL 6水平均高于健康对照组（P<0.05）。治疗第7天开始观察组血清IL 6水平明显低于对照组（P<0.05）;且观察组血清IL 6水平最高值明显低于对照组最高值（P<0.05）。结论: 丹参多酚酸盐联合常规治疗能有效降低脑梗死患者NIHSS评分,降低其血清IL 6水平,效果优于单纯常规治疗。     

铁线莲总皂苷对佐剂性关节炎大鼠的治疗作用及机制研究

摘 要 目的：探讨铁线莲总皂苷对佐剂性关节炎（AA）大鼠的治疗作用及其机制。方法: Wistar大鼠随机分为6组：正常对照组,模型对照组,阳性对照组（吲哚美辛,10 mg瘙
簚kg^-1）,铁线莲总皂苷高、中、低剂量组,每组10只。用弗氏完全佐剂建立AA大鼠模型,观察药物对大鼠体质量和足爪肿胀度的影响;测定大鼠血清中超氧化物歧化酶（SOD）、丙二醛（MDA）、一氧化氮（NO）、谷胱甘肽过氧化物酶（GSH PX）的水平,以及血清中炎症因子白介素 8（IL 8）、IL 10和肿瘤坏死因子 α（TNF α）的含量。结果: 给药后第8天开始,与模型对照组相比,铁线莲总皂苷能有效缓解大鼠体质量变化,缓解大鼠的足爪肿胀度（P＜0.05或P＜0.01）,高剂量铁线莲总皂苷与阳性对照组相比差异无统计学意义（P>0.05）,低剂量组与高、中剂量组比较差异有统计学意义（P＜0.05）。铁线莲总皂苷各给药组均能在一定程度上影响AA大鼠血清中SOD、MDA、NO和GSH PX水平,除铁线莲总皂苷低剂量组对NO指标影响不显著外,其余各组与模型对照组相比差异均有统计学意义（P＜0.05或P＜0.01）,其中MDA、NO和GSH PX水平在高、低剂量组间差异有统计学意义（P＜0.05）。与模型对照组相比,铁线莲总皂苷各组大鼠血清中IL 8和TNF α含量显著降低,IL 10含量显著升高（P＜0.05或P＜0.01）;高剂量组在调节IL 10和TNF α的作用上与阳性对照组差异无统计学意义（P>0.05）,其中IL 8和IL 10在高、低剂量组间差异有统计学意义（P＜0.05）。结论: 铁线莲总皂苷对AA具有良好的治疗作用,其机制可能与降低制脂质过氧化及抑制致炎因子有关。     

大株红景天注射液辅助治疗老年不稳定性心绞痛患者疗效及对血清LncRNA TUG1、LncRNA MIAT的影响

摘 要 目的：观察大株红景天注射液辅助治疗老年不稳定性心绞痛（UAP）的疗效，并推测其部分作用机制，为临床应用提供理论依据。方法：74例老年UAP患者随机分为对照组（35例）和红景天组（39例），两组均采用常规治疗，红景天在此基础上静滴大株红景天注射液治疗，两组疗程均为14 d。观察两组患者治疗前后心绞痛相关评分、心电图变化情况；检测患者血清中血清淀粉样蛋白A（SAA）、白细胞介素 6（IL 6）、肿瘤坏死因子 α（TNF α）、可溶性细胞间黏附因子 1（sICAM 1）、血管性假血友病因子（vWF）、P 选择素（Ps）含量，以及外周血中长链非编码RNA（LncRNA）牛磺酸上调基因1（TUG1）、LncRNA心肌梗死相关转录基因（MIAT）。 结果：治疗后两组患者心绞痛症状评分均较前明显下降（P<0.05），SAA、IL 6、TNF α、Ps、sICAM 1及vWF含量均降低，血清中LncRNA TUG1表达升高，LncRNA MIAT表达下降（P<0.05）。与对照组相比，红景天组患者的心绞痛症状评分、血清SSA、IL 6、TNF α、Ps、sICAM 1及vWF含量，及LncRNA MIAT表达下降，血清中LncRNA TUG1表达升高（P<0.05）。结论：大株红景天注射液辅助治疗老年UAP具有良好疗效，其机制可能与调节LncRNA TUG1、LncRNA MIAT表达，进而减轻炎症相关因子和血管内皮损伤相关因子表达有关。     

双歧三联活菌胶囊辅助治疗2型糖尿病疗效及对血清炎症因子的影响

摘 要 目的：探讨双歧三联活菌胶囊辅助治疗2型糖尿病（T2DM）的疗效和对患者血清炎症因子水平的影响。方法: 102例T2DM患者按入院单双号分为观察组（n=53）和对照组（n=49）。对照组予二甲双胍片0.5 g,po,tid;观察组在对照组基础上加用双歧三联活菌胶囊0.42 g,po,tid。8周为一疗程。治疗前后检测两组患者果糖胺、糖化血红蛋白和空腹血糖, 血清TNF α、脂联素的水平变化,并记录不良反应。 结果: 治疗后,两组患者果糖胺、糖化血红蛋白、空腹血糖、TNF α水平均较治疗前下降,脂联素则较治疗前显著增高（P<0.05）;且与对照组相比,对照组改善更为明显（P<0.05）。两组均未见药品不良反应发生。结论: 补充益生菌有助于T2DM患者血糖的控制,推测与降低炎症反应有关。     

地屈孕酮片治疗原因不明复发性流产患者的疗效及对细胞免疫因子的影响观察

摘 要 目的：探讨地屈孕酮片治疗原因不明复发性流产患者的疗效,及对患者细胞免疫因子的影响。方法: 不明原因复发性流产患者90例随机分为观察组和对照组各45例。对照组患者妊娠后给予注射用绒促性素治疗,观察组患者停经35d后给予地屈孕酮片治疗。比较两组患者治疗前后白细胞介素 4（IL 4）、白细胞介素 10（IL 10）、白细胞介素 17（IL 17）和干扰素（IFN γ）水平变化,以及两组治疗前后患者辅助性T淋巴细胞（Th17/CD4+）、调节性T淋巴细胞（Treg/CD4+）和辅助性T淋巴细胞/调节性T淋巴细胞（Th17/Treg）变化。观察治疗后妊娠成功率和流产率,以及药品不良反应发生情况。结果: 治疗后,两组患者血清IL 4、IL 10水平较前明显上升,IL 17和IFN γ水平则较前明显下降（P<0.05）;且观察组血清IL 4、IL 10水平高于对照组,IL 17和IFN γ水平则低于对照组（P<0.05）。治疗后,两组患者的Th17/CD4+、Th17/Treg均较前明显下降,Treg/CD4+则较前明显上升（P<0.05）;且组间比较,观察组Th17/CD4+、Th17/Treg低于对照组,Treg/CD4+高于对照组（P<0.05）。观察组妊娠率明显高于对照组（P<0.05）,流产率明显低于对照组（P<0.05）;药品不良反应发生率也低于对照组（P<0.05）。结论: 地屈孕酮片治疗原因不明复发性流产患者效果显著,可以有效改善患者的细胞免疫因子,值得临床推广使用。     

血必净联合支气管肺泡灌洗辅助治疗重症肺部感染

摘 要 目的：观察血必净联合支气管肺泡灌洗辅助治疗重症肺部感染的临床疗效及安全性。方法: 重症肺部感染患者110例按入院单双号分为观察组和对照组各55例。对照组患者在常规治疗基础上给予支气管肺泡灌洗治疗,观察组患者应用血必净联合支气管肺泡灌洗治疗。观察两组疗效和药品不良反应,应用临床肺部感染评分(CPIS) 和急性生理与慢性健康Ⅱ(APACHE Ⅱ)评分评估患者治疗前后肺部感染程度及预后。记录患者治疗或症状改善时间,检测治疗前后降钙素原(PCT)、超敏C反应蛋白（hs-CRP）和肿瘤坏死因子-α( TNF-α)等血清炎症因子水平。结果: 观察组显效率60.00%,高于对照组的43.64%（P＜0.05）。治疗后,两组患者CPIS 和APACHE Ⅱ评分较治疗前明显降低(P＜0.05),且观察组明显低于对照组(P＜0.05);两组血清PCT、hs CRP、TNF α水平均较治疗前显著下降(P＜0.05),且观察组均明显低于对照组(P＜0.05)。观察组机械通气时间、感染控制窗出现时间、呼吸衰竭纠正时间、肺部炎症基本消失时间、应用抗菌药时间均短于对照组(P＜0.05)。两组药品不良反应比较,差异无统计学意义（P＞0.05）。结论:应用血必净联合支气管肺泡灌洗辅助治疗重症肺部感染患者具有较好的临床疗效,预后改善显著,治疗时间缩短,炎症因子水平显著下降,且安全性较好。     

布地奈德福莫特罗粉吸入剂联合常规治疗稳定期支气管扩张症患者的疗效及对炎症因子和CAT评分的影响

摘 要 目的：观察布地奈德福莫特罗粉吸入剂联合常规治疗对稳定期支气管扩张症的临床疗效,及对患者血清炎症因子白细胞介素17(IL 17)、干扰素γ(IFN γ）及慢性阻塞性肺疾病评估测试(CAT)评分的影响。方法: 稳定期支气管扩张患者120例随机分为对照组和观察组各60例。对照组采用常规治疗方法,观察组在常规治疗基础上加用布地奈德福莫特罗粉吸入剂,两组疗程均为3个月。比较两组患者治疗前后急性加重次数、临床症状评分、呼吸困难评分、动脉血氧分压( PaO2)、动脉血二氧化碳分压(PaCO2)、第1秒用力呼气容积（FEV1）、用力肺活量(FVC)、呼气峰值流速(PEF)、6 min 步行试验（6MWT）、肺泡灌洗液细胞分类比例、CAT评分、血清IL 7、IFN γ水平。结果: 治疗后,观察组患者的临床症状评分、呼吸困难评分均较治疗前显著下降（P<0.05）,且观察组的临床症状评分、呼吸困难评分、呼吸加重次数均显著低于对照组治疗后（P<0.05）。治疗后,两组患者 PaO2、FEV1、6MWT均较前显著升高,CAT评分、IL 7、TNF γ浓度则较前显著降低,中性粒细胞比例明显下降,巨噬细胞比例明显上升（P<0.05）;且观察组上述指标均明显优于对照组（P＞0.05）。两组PaCO2、FVC、PEF,以及淋巴细胞比例等指标无显著变化（P>0.05）。结论: 布地奈德福莫特罗粉吸入剂对稳定期支气管扩张症疗效确切,可有效缓解临床症状,减少炎性反应。     

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.     

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.     

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.