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1.
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。  相似文献   

2.
目的 探讨喘舒片联合沙美特罗替卡松治疗支气管哮喘急性发作期的临床疗效。方法 选取2021年10月—2023年11月定州市人民医院收治的支气管哮喘症患者120例。依据用药情况分为对照组和治疗组,每组各60例。对照组患者吸入沙美特罗替卡松吸入气雾剂,1揿/次,2次/d。在对照组的基础上,治疗组口服喘舒片,2片/次,3次/d;两组用药7 d观察治疗情况。观察两组患者临床疗效,比较治疗前后两组患者症状好转时间,哮喘控制试验评分(ACT)和哮喘生活质量评分量表(AQLQ)评分,及血管内皮生长因子(VEGF)、血管细胞黏附分子(VCAM-1)、C反应蛋白(CRP)、呼气一氧化氮(FeNO)水平、用力肺活量(FVC)、第1秒用力呼气量(FEV1)和第1秒用力呼气容积占用力肺活量百分比(FEV1/FVC)指标水平。结果 治疗后,治疗组临床总有效率为96.67%,明显高于对照组(83.33%,P<0.05)。治疗后,治疗组咳嗽、喘息、胸痛、气促等症状好转时间均明显早于对照组(P<0.05)。治疗后,两组患者ACT评分、AQLQ评分比治疗前均明显升高(P<0.05),且治疗组ACT评分、AQLQ评分均明显高于对照组(P<0.05)。治疗后,两组患者VEGF、VCAM-1、CRP、FeNO水平比治疗前明显降低,而FVC、FEV1、FEV1/FVC水平明显升高(P<0.05),且治疗组患者上述指标水平明显好于对照组(P<0.05)。结论 喘舒片联合沙美特罗替卡松可极大改善哮喘急性发作期患者症状,减弱机体内炎性反应,显著提升生活质量。  相似文献   

3.
宋广浩  沈瀚  宁明哲 《安徽医药》2020,41(12):1440-1443
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。  相似文献   

4.
董英豪  杨灿  段振忠 《安徽医药》2019,40(5):566-569
目的 分析皮肌炎患者外周血Th17、Treg细胞百分比与疾病活动度的关系。方法 回顾性分析2016年12月至2017年12月驻马店市中心医院皮肤科收治的80例皮肌炎患者临床资料,以初治处于活动期40例为活动组,初治处于缓解期40例为缓解组,选择40例健康体检者为对照组。流式细胞术检测3组对象T淋巴细胞亚群(CD3+、CD3+CD4+、CD3+CD8+T细胞)、Treg/Th17细胞百分比,分析Treg/Th17细胞百分比与疾病活动度的关系。结果 初治组CD3+、CD3+CD4+、CD3+CD8+T细胞计数低于缓解组、对照组(P<0.05),缓解组CD3+、CD3+CD4+、CD3+CD8+T细胞计数高于对照组(P<0.05)。初治组CD3+细胞百分比低于缓解组、对照组(P<0.05),初治组Treg细胞百分比低于缓解组、对照组(P<0.05)。初治组Th17细胞百分比高于缓解组、对照组(P<0.05)。Th17细胞百分比与视觉模拟评分(VAS)呈负相关(r=-0.908,P<0.05),Treg细胞百分比与VAS评分呈正相关(r=0.913,P<0.05)。结论 皮肌炎患者外周血Th17细胞、Treg细胞百分比与VAS评分存在相关性,通过监测Th17、Treg细胞百分比,可监测病程、指导治疗。  相似文献   

5.
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。  相似文献   

6.
目的 探讨布地格福吸入气雾剂联合茶碱治疗慢性阻塞性肺疾病(COPD)稳定期的临床效果。方法 选取2020年1月—2021年3月天津市第五中心医院收治的96例COPD稳定期患者,随机分为对照组(48例)和治疗组(48例)。对照组口服茶碱缓释片,1片/次,2次/d。治疗组在对照组基础上经口吸入布地格福吸入气雾剂,2揿/次,2次/d。两组患者连续治疗12周。观察两组患者临床疗效,比较治疗前后两组患者6 min步行距离(6MWD)、自我评估测试(CAT)问卷、St George’s呼吸问卷(SGRQ)评分、肺功能参数第1秒用力呼气容积(FEV1)、FEV1与用力肺活量(FVC)比值(FEV1/FVC)、一氧化碳弥散量(DLCO)占预计值百分数、FEV1占预计值百分数和残气容积(RV)与肺总量(TLC)比值(RV/TLC)及呼出气一氧化氮(FeNO)浓度、外周血辅助性T细胞(Th)1与Th2比值(Th1/Th2)、血清基质金属蛋白酶-9(MMP-9)和白细胞介素-18(IL-18)水平。结果 治疗后,治疗组总有效率为95.8%,显著高于对照组的83.3%(P<0.05)。治疗后,两组6MWD均较治疗前显著增加(P<0.05),CAT问卷和SGRQ评分显著降低(P<0.05),且治疗组的6MWD和CAT问卷、SGRQ评分比对照组改善更显著(P<0.05)。治疗后,两组FEV1、FEV1/FVC、DLCO占预计值百分数及FEV1占预计值百分数均较治疗前显著升高(P<0.05),RV/TLC显著降低(P<0.05),且治疗组肺功能明显好于对照组(P<0.05)。治疗后,两组FeNO、外周血Th1/Th2及血清MMP-9、IL-18水平均显著下降(P<0.05),且治疗组降低更明显(P<0.05)。结论 布地格福吸入气雾剂联合茶碱治疗COPD稳定期整体效果显著,能安全有效地改善患者症状、生活质量及肺功能,具有一定临床推广应用价值。  相似文献   

7.
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。  相似文献   

8.
目的 探讨尪痹胶囊联合艾拉莫德治疗类风湿关节炎的临床疗效。方法 选取2020年1月—2021年1月郑州市中医院收治的130例类风湿关节炎患者,随机分为对照组(65例)和治疗组(65例)。对照组患者口服艾拉莫德片,25 mg/次,2次/d。治疗组患者在对照组基础上口服尪痹胶囊,5粒/次,3次/d。两组患者均治疗12周。观察两组患者临床疗效,比较治疗前后两组患者主要症状和体征,红细胞沉降率(ESR)、C反应蛋白(CRP)、类风湿因子(RF)和抗环瓜氨酸肽抗体(Anti-CCP)水平,肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和IL-17水平,及Th17比例、Th17/Treg值和Treg细胞比例。结果 治疗后,治疗组总有效率为96.92%,明显高于对照组的87.69%(P<0.05)。治疗后,两组关节疼痛数、关节肿胀数、晨僵时间、VAS评分均较治疗前降低,双手握力上升(P<0.05),且治疗组主要症状和体征明显好于对照组(P<0.05)。治疗后,两组ESR、CRP、RF、Anti-CCP水平均较治疗前降低(P<0.05),且治疗组比对照组降低更显著(P<0.05)。治疗后,两组TNF-α、IL-6、IL-17水平均较治疗前降低(P<0.05),且治疗组较对照组降低更显著(P<0.05)。治疗后,两组Th17比例、Th17/Treg值均降低,而Treg细胞比例均上升(P<0.05),且治疗组免疫功能明显好于对照组(P<0.05)。结论 尪痹胶囊联合艾拉莫德可以提高类风湿关节炎患者疗效,改善患者临床症状和体征,抑制炎症反应,改善免疫功能,安全性高。  相似文献   

9.
目的 探讨肺力咳合剂联合布地奈德福莫特罗治疗慢性阻塞性肺疾病急性加重期(AECOPD)的临床效果。方法 选取2018年10月—2020年9月天津医科大学宝坻临床学院收治的102例AECOPD患者,随机分为对照组(51例)和治疗组(51例)。对照组吸入布地奈德福莫特罗吸入剂,2吸/次,2次/d。治疗组口服肺力咳合剂,20 mL/次,3次/d。两组连续治疗2周。观察两组患者临床疗效,比较治疗前后两组患者肺部哮鸣音、呼吸症状缓解时间,肺功能参数第1秒用力呼气容积与用力肺活量比值(FEV1/FVC)、深吸气量与肺总量比值(IC/TLC)、一氧化碳弥散量与肺泡通气量比值(DLCO/VA)和FEV1占预计值%,咳痰的评估问卷(CASA-Q)总分,中性粒细胞与淋巴细胞比值(NLR)和呼出气一氧化氮(FeNO)浓度及血清白细胞介素-17(IL-17)、淀粉样蛋白A(SAA)和肺表面活性蛋白D(SP-D)水平。结果 治疗后,治疗组临床有效率为96.1%,显著高于对照组的84.3%(P<0.05)。治疗后,治疗组肺部哮鸣音和呼吸症状缓解时间均显著短于对照组(P<0.05)。治疗后,两组肺功能参数FEV1/FVC、IC/TLC、DLCO/VA、FEV1占预计值%和CASA-Q总分均显著升高(P<0.05),并均以治疗组改善更显著(P<0.05)。治疗后,两组患者NLR和FeNO浓度及血清IL-17、SAA、SP-D水平均显著低于治疗前(P<0.05),且治疗组对NLR和FeNO浓度及血清IL-17、SAA、SP-D水平的降低作用较对照组更显著(P<0.05)。结论 肺力咳合剂联合布地奈德福莫特罗治疗AECOPD的整体疗效确切,可安全、有效且迅速地缓解患者症状,改善气流受限,抑制体内炎症反应。  相似文献   

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目的 探讨依巴斯汀联合马齿苋治疗特应性皮炎(atopic dermatitis,AD)的临床疗效及对miR-186-5p、miR-409-3p水平、免疫状态的影响。方法 2014年10月至2017年10月在新疆医科大学附属中医医院就诊的112例AD患者被随机分为对照组和观察组,每组56例。对照组口服依巴斯汀,观察组在对照组基础上进行马齿苋塌渍治疗。比较治疗前、治疗2周、4周的症状评分和临床有效率,比较治疗前后外周血Th17/Treg、IL17水平以及皮损边缘皮肤标本的miR-186-5p、miR-409-3p表达。结果 治疗前,2组各指标均无显著差异,治疗2,4周后,观察组症状评分显著低于对照组(P<0.05);治疗2,4周时观察组的总有效率分别为66.07%,80.36%,显著高于对照组35.72%,57.14%(P<0.05)。治疗后2组Th17%、Th17/Treg、IL-17均显著下降,且观察组显著低于对照组(P<0.05);2组miR-186-5p、miR-409-3p表达均显著下降,且观察组显著低于对照组(P<0.05)。结论 依巴斯汀联合马齿苋能有效改善AD临床症状,提高疗效,下调皮肤中miR-186-5p、miR-409-3p的表达,降低血清Th17/Treg表达,改善炎症状态。  相似文献   

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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.
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.
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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.  相似文献   

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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.  相似文献   

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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.  相似文献   

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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.  相似文献   

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