桑白皮多糖对RSV肺炎小鼠肺组织病理形态和外周血T细胞亚群的影响

目的 通过研究桑白皮多糖对RSV肺炎BALB/c小鼠肺组织病理形态和外周血T细胞亚群的影响，探讨桑白皮多糖对BALB/c小鼠RSV肺炎的干预机制。 方法 BALB/c小鼠随机分为正常组、模型组、高剂量组、中剂量组、低剂量组，每组10只；除正常组外，用RSV(long株)经鼻腔接种，建立小鼠RSV肺炎模型 。于感染当天，高、中、剂量组分别予桑白皮多糖182mg/(kg?d)、91mg/(kg?d)、45.5mg/(kg?d)灌胃，正常组与模型组予等体积生理盐水灌胃，1次/ d， 于感染第7天取外周血进行T细胞亚群的检测及肺组织进行HE染色。 结果 桑白皮多糖能有效地减少肺泡壁炎细胞的浸润，改善肺组织的炎症状况。高、中、低剂量组与模型组比较，高剂量组CD3 T细胞百分率、CD4 T/CD8 T存在统计学差异(P<0.05)；中剂量组CD3 T细胞百分率、 CD4 T细胞百分率、CD4 T/CD8 T均存在统计学差异(P<0.05) ；低剂量组只有CD4 T/CD8 T存在统计学差异(P<0.05)。 结论：桑白皮多糖可以改善肺炎小鼠肺组织病理变化，能够调节机体细胞免疫。     

黄芩苷改善呼吸道合胞病毒肺炎幼鼠肺损伤的作用机制

目的探讨黄芩苷对呼吸道合胞病毒( RSV)肺炎幼鼠肺损伤的改善作用及其可能作用机制。方法 2022年 3月至 2023年 7月自杭州子源实验动物科技有限公司购入 55只 4周龄 SPF级雄性 SD大鼠,选取其中 45只鼻腔接种 50 μLRSV建立 RSV肺炎幼鼠模型,造模成功幼鼠采用随机数字表法分为模型组、黄芩苷低、中和高剂量组,各 10只,另设对照组(10只)给予相应药物进行干预, 1次/天,连续 7d。称取各组幼鼠肺质量,并计算肺指数;肺组织烘干后计算肺组织湿 /干比(W/D)评定肺水,肿; ELISA法检测幼鼠肺泡灌洗液中肿瘤坏死因子 -α(TNF-α)、白细胞介素 -1β(IL-1β)和白细胞介素 -6(IL-6)水平;流式细胞仪检测幼鼠外周血中 T细胞亚群; HE染色观察各组大鼠肺组织病理变化; RT-qPCR和蛋白质印迹法分别检测大鼠肺组织中 p38丝裂原活化蛋白激酶( p38MAPK)及其磷酸化 mRNA和蛋白表达情况。结果黄芩苷低剂量组幼鼠肺指数、肺组织 W/D、TNF-α、IL-1β、IL-6、CD4+CD4+/CD8+p38MAPK mRNA表达和 p-p38MAPK蛋白表达水平［( 1.05±0.06)%、(6.13±0.40)、(392.37±20.82)ng/L、(72.85±42)ng/L3.29±8.59)ng/L、(25.85±1.50)%、(3.98±0.33、0.65±0.08)］,中剂量组［( 0.81±0.06)%、(5.62±0.41)、(308.17±18.87)ng/L、(57.59±4.14)ng/L、(82.36±6.05)ng/L、(23.59±1.30)%、(3.36±0.36、0.54±0.06)］,高剂量组［( 0.72± 0.05)%、(4.03±0.30)、(246.87±16.44)ng/L、(42.15±3.33)ng/L、(56.17±5.13)ng/L、(20.16±0.99)%、(2.17±0.24、0.42±0.05)］均显著低于模型组［( 1.43±0.09)%、(7.82±0.37)、(487.85±25.77)ng/L、(91.24±7.41)ng/L、(132.75±9.70)ng/L、(27.24±1.72)%、(4.75±0.40、0.78±0.11)］(P<0.05);黄芩苷低剂量组幼鼠体质量、 CD3+水平［( 78.05±1.46)g、(49.66±0.89)%］中剂量组［( 86.04±2.31) g、(51.17±1.04)%］,高剂量组［( 99.34±2.08)g、(54.87±1.25)%］均显著高于模型组［( 72.53±1.56)g(46.25±0.82)%］(P<0.05)。结论黄芩苷能够降低 RSV肺炎幼鼠炎症因子水平,调节 T淋巴细胞亚群比例,减轻肺损伤,可能是通过影响 p38MAPK信号通路发挥作用。     

血吸虫可溶性虫卵抗原对哮喘的抑制作用及机制研究

目的研究血吸虫可溶性虫卵抗原(SEA)对哮喘发生的抑制作用及免疫调节机制。方法BALB/C小鼠腹腔及足垫注射SEA 50μg/只,每周1次,共4次。对照组注射生理盐水。然后用卵清白蛋白(OVA)诱导小鼠产生过敏性哮喘,剖杀小鼠,取肺组织进行病理学检查;收集支气管肺泡灌洗液(BALF),涂片、染色后进行细胞分类计数;分离脾细胞,用流式细胞仪检测CD4+CD25+调节性T细胞(CD4+CD25+Treg)占CD4+T细胞的比例。结果 SEA免疫并OVA致哮喘组小鼠肺组织炎症明显轻于OVA单纯哮喘对照组,只有少量炎性细胞浸润。BALF涂片染色后发现SEA免疫组BALF中的细胞密度低于对照组,其中嗜酸性粒细胞占总细胞数的比例(2.2±1.5)%明显低于对照组(19.9±4.1)%,差异有统计学意义(P<0.05)。流式细胞仪检测结果发现SEA免疫组小鼠脾细胞中CD4+CD25+Treg占CD4+T细胞总数的(32.2±2.2)%,明显高于对照组(27.4±2.9)%,差异有统计学意义(P<0.05)。结论 SEA对哮喘的发生有一定的抑制作用,其机制可能是通过CD4+CD25+调节性T细胞影响机体的免疫调节机制。     

加味逍遥散对慢性应激小鼠学习记忆和免疫细胞的影响

目的观察加味逍遥散对慢性应激小鼠学习记忆及免疫细胞的影响,为探讨加味逍遥散的药理作用,提供临床实验依据。方法BALB/c小鼠随机分为5组:正常对照组、应激组、逍遥散组、加味逍遥散低剂量组、加味逍遥散高剂量组。通过水迷宫实验观察小鼠学习记忆能力。采用流式细胞仪检测小鼠脾组织中CD4、CD8的含量。结果加味逍遥散高、低剂量组、逍遥散组与应激组相比均能缩短逃避潜伏期(P<0.01)、增加第一象限停留时间百分比(P<0.01)。小鼠脾淋巴细胞悬液中CD4+T细胞高于应激组(P<0.05),而CD8+T细胞低于应激组(P<0.05)及CD4/CD8比值低于应激组(P<0.05)。结论逍遥散和加味逍遥散均具有显著拮抗因应激所致的学习记忆能力和免疫功能的改变,以高剂量加味逍遥散作用最佳。     

白芍总苷通过白细胞介素 -6/信号转导及转录激活蛋白 3信号通路对脂多糖诱导的急性肺炎小鼠炎症反应的影响

目的探讨白芍总苷( TGP)通过白细胞介素 -6/信号转导及转录激活蛋白 3(IL-6/STAT3)信号通路对脂多糖诱导的急性肺炎小鼠炎症反应的影响。方法本研究起止时间为 2019年 10月至 2020年 2月。选择 SPF级雄性小鼠 50只,采用随机数字表法将小鼠随机分为五组,对照组、急性肺炎模型组、 TGP低剂量组、 TGP中剂量组和 TGP高剂量组。采用苏木精 -伊红( HE)染色观察各组小鼠肺组织病理形态学;采用酶联免疫吸附测定( ELISA)检测各组小鼠肺组织肿瘤坏死因子 -α(TNF-α)、白细胞介素( IL)-1β含量;采用蛋白质印迹( Western blotting)检测各组小鼠肺组织 IL-6、STAT3、磷酸化信号转导及转录激活蛋白 3(p-STAT3)的蛋白表达水平;采用实时荧光定量 PCR(qRT-PCR)检测各组小鼠肺组织 IL-6、STAT3 mRNA表达水平。结果模型组小鼠肺组织结构被破坏,肺泡间隔增厚,大量炎性细胞浸润; TGP药物组病理改变较模型组均存在不同程度改善,白芍总苷高剂量组肺组织仅存在少量炎性细胞浸润。与对照组( 45.12±9.73)ng/L、(21.38±2.13)ng/L相比,模型组及 TGP各剂量组小鼠肺组织 TNF-α(89.30±9.26)ng/L,(84.32±5.08)ng/L,(75.36±4.67)ng/L,(64.06±5.90)ng/L、IL-1β含量( 59.69±3.60)ng/L,(56.87±     

雷帕霉素诱导Balb/c小鼠CD4~+ CD25~+ foxp3~+调节性T细胞增殖

目的探讨雷帕霉素对Balb/c小鼠CD4+ CD25+ foxp3+调节性T细胞的作用。方法取8wk龄的SPF级Balb/c小鼠30只,随机分为两组,实验组每只灌胃雷帕霉素0.4mg.d-1,对照组灌胃每天予等体积无菌水,共3wk。无菌条件下肝素抗凝心脏采血,分离脾脏,制备单细胞悬液。采用流式细胞仪检测小鼠外周血和脾细胞CD4+CD25+T细胞,实时定量PCR检测小鼠脾细胞foxp3 mRNA的表达。结果实验组小鼠外周血和脾细胞中CD4+CD25+T细胞的比例分别为(9.95±4.65)%和(24.13±10.06)%,对照组小鼠外周血和脾细胞中CD4+CD25+T细胞的比例分别为(5.01±1.49)%和(8.48±3.19)%,差异均有显著性(P<0.01)。实验组小鼠脾细胞foxp3 mRNA的表达水平明显高于对照组,是对照组的6.029倍,差异有显著性(P<0.01)。结论雷帕霉素能够明显诱导Balb/c小鼠体内CD4+CD25+T细胞的增殖,并能提高foxp3+ mRNA的表达。     

杂色曲霉素对小鼠胸腺和脾脏转录因子Foxp3~+调节性T淋巴细胞的影响

目的探讨杂色曲霉素(ST)对机体免疫调节功能的影响。方法BALB/c小鼠随机分为正常对照组、溶剂对照组、ST3,30,300和3000μg·kg-1组。小鼠ip给药24h后,处死取胸腺和脾脏,采用流式细胞术测定胸腺和脾脏细胞中CD4+和CD8+T淋巴细胞及转录因子Foxp3阳性(Foxp3+)调节性T淋巴细胞的百分率,免疫组织化学法检测胸腺和脾脏组织中Foxp3+调节性T淋巴细胞数量,Western蛋白印迹法和RT-PCR分别测定胸腺和脾脏组织中Foxp3蛋白和mRNA的表达。结果溶剂对照组与正常对照组比较,小鼠胸腺和脾脏CD4+,CD8+和Foxp3+T淋巴细胞百分率均无明显差异。与溶剂对照组比较,ST3μg·kg-1组胸腺CD8+T淋巴细胞百分率降低,ST3和30μg·kg-1组脾脏CD4+和CD8+T淋巴细胞百分率明显升高,ST300和3000μg·kg-1组胸腺和脾脏CD4+和CD8+T淋巴细胞百分率无明显变化。在ST3～3000μg·kg-1内,胸腺和脾脏细胞中Foxp3+调节性T淋巴细胞百分率、胸腺和脾脏组织内Foxp3+调节性T淋巴细胞数量、Foxp3蛋白和mRNA表达均随ST浓度的增高而增加。结论ST可诱导小鼠淋巴器官内Foxp3+调节性T淋巴细胞数量增加,从而影响机体免疫耐受功能。     

RSV毛细支气管炎患儿外周血CD4+ CD25+调节性T细胞与Th17细胞功能变化及意义

目的观察RSV毛细支气管患儿外周血CD4+CD25+调节性T细胞与Th17细胞及其分泌因子IL-10、TGF-β、IL-17水平并探讨与RSV毛细支气管炎发病的关系。方法采集33例RSV阳性毛细支气管炎患儿外周血,采用流式细胞仪检测外周血CD4+CD25+调节性T细胞、Th17细胞百分率,ELISA法检测血浆IL-10、TGF-β、IL-17的水平。28例非RSV感染的普通肺炎患儿作为阳性对照,26例健康儿童为正常对照组。结果 RSV毛细支气管炎患儿外周血CD4+CD25+调节性T细胞、IL-10、TGF-β水平低于肺炎组及正常对照组(P<0.05),毛支组Th17、IL-17水平高于肺炎组与正常对照组(P<0.05)。结论外周血CD4+CD25+调节性T细胞与Th1细胞7表达失衡,可能是RSV毛细支气管炎发病机制之一。     

LW-AFC对环磷酰胺处理小鼠免疫功能的影响

目的探讨LW-AFC对免疫功能低下小鼠是否有改善作用。方法昆明小鼠ip给予环磷酰胺(CTX)0.02g·kg-1,连续10d,制备免疫功能低下小鼠模型。六味地黄(LW)浓缩丸(1.4g·kg-1)和LW-AFC(0.2,0.4和0.8g·kg-1)组小鼠在每次给予CTX后ig给予相应药物,连续10d。监测小鼠体重,以及胸腺和脾脏重量变化,并计算胸腺和脾脏系数;[3H]TdR掺入法检测脾淋巴细胞增殖反应,MTT法检测脾脏自然杀伤(NK)细胞杀伤活性,流式细胞术检测脾淋巴细胞中CD4+CD8-和CD4-CD8+T细胞亚群百分率,并计算CD4+/CD8+T细胞亚群比值。结果与正常对照组比较,模型组小鼠胸腺和脾重量及其系数明显降低,体重增长显著缓慢;LW和LW-AFC对小鼠体重增长缓慢、胸腺重量及其系数降低无明显改善作用;LW-AFC0.2g·kg-1对CTX导致的脾重及系数降低有明显改善(P<0.05)。模型组小鼠脾淋巴细胞自发增殖反应、刀豆蛋白A(ConA)和脂多糖(LPS)诱导的脾细胞增殖反应与正常对照组比较均明显降低,[3H]TdR掺入值由正常对照组的6115±441,19432±1778和(23345±7296)cpm分别降低为2741±340,9210±1387和(3983±263)cpm;与模型组比较,LW-AFC0.8g·kg-1对脾淋巴细胞自发增殖反应有明显的改善作用;LW浓缩丸和LW-AFC对ConA诱导的脾细胞增殖反应均具有明显的促进作用,[3H]TdR掺入值分别为13996±5161,27550±2356,15427±1444和(27333±1701)cpm;对LPS诱导的脾细胞增殖降低无改善作用,甚至低于CTX模型组(P<0.01)。模型组小鼠NK细胞杀伤活性由正常对照组的(39.5±0.5)%降低为(37.0±1.0)%,LW和LW-AFC明显促进小鼠NK细胞杀伤活性,杀伤率分别为(40.9±0.6)%,(39.7±0.8)%,(42.4±0.5)%和(39.8±0.9)%。与正常对照组比较,模型组小鼠脾脏CD3+,CD4+CD8-和CD4-CD8+T细胞百分率明显增加,CD4+/CD8+比值无明显变化;LW浓缩丸和LW-AFC可使CTX导致的升高的CD3+,CD4+CD8-和CD4-CD8+T细胞百分率明显降低,并可明显降低CD4+/CD8+比值。结论 LW-AFC对CTX所致小鼠免疫功能低下具有一定的改善作用。     

三氧化二砷对MRL/lpr小鼠免疫功能和肾脏组织病理变化的影响(英文)

目的研究三氧化二砷(As2O3)对MRL/lpr小鼠免疫功能和肾脏组织病理变化的影响。方法45只MRL/lpr狼疮小鼠ip给予环磷酰胺50 mg·kg-1(每周1次)和As2O30.8 mg·kg-1,每天1次,共2个月。用ELISA法检测血清抗双链DNA(dsDNA)抗体、干扰素γ(IFN-γ)和白细胞介素12(IL-12)浓度;用流式细胞术测定脾CD3+,CD19+,CD3+CD4+和CD3+CD8+细胞亚群的百分比;用PAS染色法观察肾组织病理变化;用免疫荧光方法检测肾组织IgG和补体C3的表达。结果与给药前比较,给药2个月后,正常对照组血清抗dsDNA抗体水平升高,由给药前1.18±0.26升高至1.80±0.26(P<0.01),As2O3和环磷酰胺组该抗体水平明显降低,分别由给药前1.14±0.58和1.09±0.22降低至0.92±0.06和0.67±0.14(P<0.05,P<0.01)。与正常对照组比较:①As2O3和环磷酰胺组血清抗ds-DNA抗体、IFN-γ和IL-12浓度明显降低(P<0.05),环磷酰胺组抗ds-DNA抗体比As2O3组显著降低(P<0.01);②As2O3组CD3+,CD3+CD4+和CD19+细胞百分率明显降低(P<0.01),环磷酰胺组CD3+,CD3+CD8+和CD19+细胞百分率明显降低(P<0.01);As2O3组CD3+CD4+细胞百分率明显降低(P<0.01);③As2O3和环磷酰胺组小鼠肾小球细胞计数和活动度积分明显降低(P<0.05,P<0.01),As2O3和环磷酰胺组无显著差异;④As2O3和环磷酰胺组肾IgG表达明显降低(P<0.05),补体C3表达无明显差异,As2O3和环磷酰胺组之间无显著性差异。结论As2O3能降低MRL/lpr狼疮小鼠血清抗ds-DNA抗体水平,抑制T,B和Th细胞活化和增殖,降低血清IFN-γ和IL-12水平,从而缓解狼疮肾炎的病理变化。     

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.     

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.     

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.     

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.