右美托咪定地佐辛单独或联合用药对腔镜下胃癌根治患者术后苏醒期的影响

目的 评价右美托咪定、地佐辛单独或联合用药对全麻腔镜胃癌根治患者术后苏醒期的影响。方法 选择2015年3月至2016年6月安徽省立医院收治的腔镜胃癌根治术患者80例,随机分为对照组（C组）、右美托咪定组（DEX组）、地佐辛组（DEZ组）和右美托咪定+地佐辛组（DD组）,每组20例。DEX、DD组于麻醉诱导前15分钟时静脉注射右美托咪定,DEZ组和DD组关腹时静脉注射地佐辛,C组关腹时静脉注射生理盐水。记录入PACU（T₀）、吸痰拔管（T₁）、拔管后5分钟（T₂）及10分钟（T₃）的平均动脉压（MAP）、心率（HR）;记录拔管后10分钟（T₃）、30分钟（T₄）、60分钟（T₅）的VAS、Ramsay评分。结果 同C组相比,T₀～T₃时DEX、DEZ、DD组MAP降低,DEX和DD组HR减慢（P<0.05）,T₃～T₅时DEX、DEZ和DD组VAS评分降低,Ramsay镇静评分增加（P<0.05）。同C组比较,其他各组躁动率和寒战发生率显著降低（P<0.05）,DD组与其他各组比较,躁动率和寒战发生率显著降低（P<0.05）。结论 右美托咪定、地佐辛单独或复合用药可使腔镜胃癌根治患者术后苏醒期血流动力学平稳,拔管后躁动和寒战发生率降低,复合用药效果更佳。     

右美托咪定辅助臂丛麻醉的镇静效果及安全性

目的 观察右美托咪定辅助臂丛麻醉的镇静效果和安全性。方法 选取2014年2月至2015年10月上海交通大学医学院附属第九人民医院行臂丛麻醉手术的120例患者为研究对象,采用随机双盲法分为A、B、C组,每组40例。A组术前予静脉注射咪达唑仑0.04 mg/kg;B组在阻滞前10 min静脉泵入0.5μg/kg右美托咪定,10 min泵完;C组在阻滞前10 min静脉泵入0.5μg/kg右美托咪定,10 min泵完,同时术前静脉注射咪达唑仑0.04 mg/kg。记录3组患者给药前（T₀）、给药10 min后（T₁）、20 min后（T₂）、30 min后（T₃）、60 min后（T₄）以及手术结束时（T₅）的心率（HR）、平均动脉压（MAP）、血氧饱和度（SpO₂）及警觉/镇静（OAA/S）评分。结果 与B、C两组比较,A组患者的感觉完全阻滞时间、运动完全阻滞时间显著缩短,差异有统计学意义（F=5.133、5.849,P=0.007、0.004）。与给药前（T₀）HR、MAP和OAA/S评分相比,A组仅T₁时显著降低,C组T₁～T₄均显著降低（P均<0.05）;B组各个时刻均保持平稳（P均>0.05）;组间上述各指标比较,A组患者T₁时刻低于B组,C组患者T₁～T₄时刻均低于B组,且T₂～T₄时刻低于A组（P均<0.05）;3组的SpO₂比较,差异无统计学意义（P>0.05）;C组患者术中因心率减慢而给予阿托品治疗的例数多于A、B两组,差异有统计学意义（χ²=7.50,P=0.02）。结论 右美托咪定辅助臂丛神经阻滞具有较高的镇静效果和安全性能。     

咪达唑仑联合丙泊酚麻醉对腹腔镜胆囊切除术后患者恢复的影响

目的 探究咪达唑仑联合丙泊酚对腹腔镜胆囊切除术后患者恢复的影响。方法 选择2019年4月至2021年1月期间入院行腹腔镜胆囊切除术的患者162例，根据不同麻醉方式的将其分为对照组（实施咪达唑仑麻醉）和观察组（实施咪达唑仑联合丙泊酚麻醉），各81例。对比两组手术前后应激指标水平，术前（T₀）、术后24 h（T₁）及48 h（T₂）的MoCA评分，T₀、术后第1天（T₃）、2天（T₄）的术后相关恢复情况。结果 观察组患者的术后Cor、NE水平及睁眼、拔管、定向力恢复时间、不良反应发生率均低于对照组（P<0.05）；T₁、T₂时观察组的MMSE评分、T₃、T₄时的睡眠质量评分均高于对照组（P<0.05）。结论 咪达唑仑联合丙泊酚用于腹腔镜胆囊切除术安全性高，患者术后恢复良好。     

右美托咪定复合舒芬太尼对心脏手术快通道麻醉术后镇痛效果及血清C反应蛋白的影响

目的 评价右美托咪定复合舒芬太尼对婴幼儿心脏手术快通道麻醉术后镇痛效果及血清C反应蛋白（CRP）的影响。方法 选择2017年1月至2018年1月在河南科技大学第一附属医院行先天性心脏病房缺和室缺修补术的患儿60例,采用随机数字表法分为右美托咪定复合舒芬太尼镇痛组（Ⅰ组）和舒芬太尼镇痛组（Ⅱ组）,每组30例。Ⅰ组患儿于缝皮前20 min开始静脉泵注右美托咪定1 μg/（kg·h）,至手术结束,Ⅱ组患儿给予等容量生理盐水。术后镇痛泵药液配方：Ⅰ组为右美托咪定37.5 μg/kg+舒芬太尼2.5 μg/kg+托烷司琼0.1 mg/kg,Ⅱ组为舒芬太尼2.5 μg/kg+托烷司琼0.1 mg/kg,均加生理盐水至100 mL,泵速2 mL/h。记录术毕（T₁）、苏醒（T₂）、拔管（T₃）、术后第6小时（T₅）、术后第24小时（T₆）、术后第48小时（T₇）的心率（HR）、平均动脉压（MAP）;记录术后4 h （T₄）、T₅、T₆、T₇疼痛行为量表（FLACC）评分和Ramsay镇静评分;记录术前（T₀）、T₅、T₆、T₇的血清CRP水平;记录术后48 h内不良反应的发生情况。结果 Ⅱ组患儿在T₂、T₃、T₅、T₆时点的MAP和HR均高于Ⅰ组（MAP：F_组间=10.105,P=0.034;HR：F_组间=10.830,P=0.030）;Ⅰ组患儿在T₄、T₅、T₆时点FLACC评分低于Ⅱ组（F_组间=23.091,P=0.001）,Ramsay镇静评分高于Ⅱ组（F_组间=21.534,P=0.002）;Ⅱ组患儿T₆、T₇时点血清CRP水平高于I组（F_组间=14.981,P=0.018）。与Ⅱ组比较,Ⅰ组患儿术后48 h内恶心、呕吐发生率降低,差异有统计学意义（P<0.05）。结论 右美托咪定复合舒芬太尼用于婴幼儿心脏手术快通道麻醉,术后镇痛安全有效,不良反应少,术后应激反应减轻。     

右美托咪定对体外循环下心脏瓣膜置换术患者的脑保护作用

目的 研究右美托咪定对体外循环（CPB）下心脏瓣膜置换术患者的脑保护作用。方法 以2015年1月-2015年12月于郑州市第七人民医院择期进行CPB下心脏瓣膜置换手术的患者80例为研究对象,根据实施手术的时间顺序分为观察组和对照组,每组40例,观察组在麻醉诱导前及手术中使用右美托咪定,对照组给予相同剂量的生理盐水,比较两组的麻醉诱导前（T₀）、升主动脉开放时（T₁）、CPB结束后10 min（T₂）以及术后6 h时（T₃）4个时间点的动脉-静脉血氧含量差（Da-jvO₂）、颈内静脉血氧饱和度（SjvO₂）以及脑氧摄取率（CERO₂）、血浆髓鞘碱性蛋白（MBP）、血清神经元特异性烯醇化酶（NSE）和S100β蛋白水平;手术前及手术后5 d的简易智力量表（MMSE）评分及认知功能障碍（POCD）发生率。结果 T₀和T₃时,两组的SjvO₂、Da-jvO₂和CERO₂比较,差异无统计学意义;T₁时,两组的SjvO₂较T₀时升高（P<0.05）,Da-jvO₂和CERO₂较T₀时降低（P<0.05）;T₁和T₂时,观察组的SjvO₂高于对照组,Da-jvO₂和CERO₂低于对照组（P<0.05）;T₂、T₃时,观察组和对照组的MBP水平均高于T₀时（P<0.05）,且观察组MBP水平低于对照组（P<0.05）;T₁、T₂、T₃时,观察组和对照组的NSE和S100β水平均较T₀时显著升高（P<0.05）,观察组的NSE水平在T₁、T₂、T₃时均低于对照组（P<0.05）,S-100β水平在T₂、T₃时均低于对照组（P<0.05）;术后5 d,观察组的MMSE评分与术前比较,差异无统计学意义（P<0.05）,对照组的MMSE评分显著低于术前（P<0.05）;观察组术后7 d的MMSE评分高于对照组,POCD发生率低于对照组（P<0.05）。结论 CPB下心脏瓣膜置换术患者术中使用右美托咪定可显著改善患者的脑缺血缺氧状态,减轻脑损伤。     

右美托咪定对腹腔镜结直肠癌根治术患者术后转归的影响

目的 探讨盐酸右美托咪定注射液对腹腔镜结直肠癌根治术患者术后转归的影响。方法 选取2015年6月-2017年6月眉山市人民医院行腹腔镜结直肠癌根治术患者160例作为研究对象，按随机数字表法将患者分为对照组和观察组，每组各80例。两组患者均采用全身麻醉，观察组在此基础上于麻醉诱导前10 min采用微量注射泵静脉输注盐酸右美托咪定注射液0.5 μg/（kg·h），10 min内泵完，再以0.5 μg/（kg·h）维持至手术结束。对照组按照相同的输注方式给予相同剂量的生理盐水。比较两组术后复苏指标、不同时间点血流动力学指标、镇痛及镇静效果分数。结果 术后两组患者睁眼时间、呼吸恢复时间、拔管时间差异无统计学意义；观察组躁动评分显著低于对照组（P<0.05）。治疗后，T₀-T₃时刻两组患者平均动脉压（MAP）、心率（HR）水平先降低再升高最终又降低，且T₁、T₂时刻观察组明显低于对照组（P<0.05）。术后观察组患者Ramsay镇静评分、静息及咳嗽VAS评分均明显降低于对照组（P<0.05）。结论 盐酸右美托咪定注射液可显著减少腹腔镜结直肠癌根治术的应激反应，改善血流动力学，镇静镇痛效果显著，减少复苏期躁动的发生，且未增加不良反应，有利于患者术后转归。     

右美托咪定对妇科腹腔镜手术患者围术期炎症因子及应激反应的影响

目的 探讨右美托咪定对妇科腹腔镜手术患者围术期炎症因子及应激反应的影响。方法 选择180例妇科腹腔镜手术患者,随机分为两组,每组90例。对照组患者静脉输注0.5 μg/kg舒芬太尼、1.8 mg/kg丙泊酚、0.6 mg/kg罗库溴铵进行麻醉诱导,术中吸入七氟醚行麻醉维持,并间断静脉推注顺苯磺阿曲库铵维持肌松。观察组麻醉诱导前静脉泵注0.5 μg/kg右美托咪定负荷剂量,之后以0.5 μg/（kg·h）输注至术毕前10 min,其余麻醉方法与对照组相同。观察麻醉诱导前10 min（T₀）、气管插管后即刻（T₁）、建立气腹时（T₂）、气腹建立30 min后（T₃）、手术结束时（T₄）5个时间点的血流动动力学变化情况,使用酶联免疫吸附法检测炎症指标,以及血管紧张素Ⅱ、皮质醇及醛固酮等应激反应指标。结果 与T₀时间点比较,观察组T₁～T₃ 心率（HR）均明显下降（P<0.05）,对照组T₁～T₃ HR均明显上升（P<0.05）,对照组发生心动过速1例,观察组未发生;与T₀时间点比较,观察组T₁～T₄有创平均动脉压（MAP）未发生明显变化,对照组T₁～T₄ MAP明显上升,组间比较差异明显（P<0.05）;与T₀时间点比较,两组的IL-6、IL-10及TFN-α均明显上升,而对照组上升程度明显高于观察组（P<0.05）;与T₀时间点比较,两组的血管紧张素Ⅱ、皮质醇及醛固酮均明显上升,且对照组上升程度明显高于观察组（P<0.05）。结论 麻醉诱导前静脉泵注0.5 μg/kg右美托咪定负荷剂量,之后以0.5 μg/（kg·h）输注至术毕前10 min,可以维持妇科腹腔镜手术围术期的血流动力学稳定,抑制围术期炎症反应及应激反应。     

丙泊酚与依托咪酯乳剂在颅脑损伤合并肺部感染患者纤维支气管镜治疗中的镇静效果及安全性评估

目的 观察丙泊酚与依托咪酯乳剂在颅脑损伤合并肺部感染患者纤维支气管镜治疗中的镇静效果及安全性。方法 选取河北医科大学第二医院2019年1月一2021年8月收治的重症医学科（ICU）机械通气颅脑损伤合并肺部感染患者84例为研究对象,按照用药方案不同分为丙泊酚组和依托咪酯组,每组各42例。两组均给予纤维支气管镜治疗,丙泊酚组给予丙泊酚乳状注射液1~2 mg·kg^-1,人工缓慢静推3~5 min。依托咪酯组给予依托咪酯中/长链脂肪乳注射液0.2~0.4 mg·kg^-1,缓慢静推。操作中若患者躁动明显或呛咳剧烈影响进境,或气管壁出血,则追加丙泊酚30mg或依托咪酯6mg。比较两组给药前5 min （T₀）、给药后-入镜即刻（T₁）、入镜后3 min （T₂）、入镜后10 min （T₃）、撤镜即刻（T₄）、术毕5 min （T₅）时脑电双频谱指数（BIS）、心率（HR）、呼吸频率（RR）、平均动脉压（MAP）、血氧饱和度（SpO₂）、脑氧饱和度（rSO₂）差异,比较两组药物平均使用量、追加药物次数、麻醉起效时间、不良反应发生情况及纤维支气管镜操作医生对镇静效果的满意度。结果 T₁、T₄、T₅时两组BIS均低于本组T₀时,T₂、T₃时高于本组T₁时（P<0.05）;T₀、T₂、T₄、T₅时两组BIS差异无统计学意义（P>0.05）;T₁、T₃时丙泊酚组BIS低于依托咪酯组（P<0.05）;T₁、T₂、T₃、T₄时丙泊酚组HR、MAP低于依托咪酯组（P<0.05）;T₀、T₅时两组HR、MAP差异无统计学意义（P>0.05）;T₀、T₁、T₂、T₃、T₄、T₅时两组RR、SpO₂、rSO₂差异无统计学意义（P>0.05）;丙泊酚组药物平均使用量多于依托咪酯组,追加药物次数少于依托咪酯组（P<0.05）;两组麻醉起效时间差异无统计学意义（P>0.05）;依托咪酯组呛咳反应发生率高于丙泊酚组（P<0.05）;两组呼吸抑制发生率、躁动发生率差、纤维支气管镜操作医生对镇静效果满意度差异无统计学意义（P>0.05）。结论 丙泊酚与依托咪酯乳剂在ICU机械通气颅脑损伤合并肺部感染患者行纤维支气管镜治疗中均具有良好镇静效果,其中依托咪酯药物平均使用量较少,对HR、MAP、BIS影响较小,但追加药物频次、呛咳反应发生率较高。     

盐酸右美托咪定对ICU患者气管插管应激反应的影响

目的 探讨盐酸右美托咪定对ICU患者气管插管应激性反应的影响。方法 选取解放军昆明总医院2015年1月-2016年1月ICU病房收治的危重症患者76例作为研究对象，按随机数字表法分为对照组和观察组，每组38例，两组均于气管插管前进行桡动脉穿刺，并建立静脉通道，观察组静脉泵注盐酸右美托咪定0.5 μg/kg，持续10 min，对照组静脉泵注等量生理盐水，随后两组均静脉滴注适量顺-阿曲库铵和丙泊酚。观察两组麻醉用药剂量；检测两组插管前（T₁）、插管后（T₂）、插管后3 min（T₃）及插管后5 min（T₄）时刻患者动脉压（MAP）、心率（HR）、血浆皮质酮水平的变化。结果 两组丙泊酚、顺-阿曲库铵麻醉用药剂量比较差异不显著；观察组T₃、T₄时刻MAP、HR、血浆皮质酮水平均显著低于对照组（P<0.05）。结论 在ICU患者气管插管中应用盐酸右美托咪定可维持血浆皮质醇水平、血流动力学稳定。     

右美托咪定对老年患者深度麻醉后血流动力学、外周血高迁移率族蛋白B1的影响

摘 要 目的：研究右美托咪定对老年患者深度麻醉后血流动力学、外周血高迁移率族蛋白B1（HMGB1）的影响。方法: 76例行腹部手术的老年患者随机分为观察组和对照组,每组38例。在麻醉诱导前观察组静滴右美托咪定,对照组使用等量的0.9%氯化钠注射液。比较两组患者不同时间点吸入七氟烷的浓度,以及麻醉诱导、手术结束时的血流动力学（平均动脉压、心率、心指数、心输出量）、白细胞介素-1β（IL-1β）、HMGB1水平变化,观察两组呼吸恢复时间、睁眼时间及拔管时间,比较两组苏醒情况和药品不良反应。结果: T1时,两组患者吸入七氟烷的浓度均较T₀时降低,T₂、T₃时,两组患者吸入七氟烷的浓度均较T₀、T₁时有所上升,两组组内不同时段比较差异具有统计学意义（P<0.05）;且观察组患者在T₁、T₂、T₃时吸入七氟烷的浓度明显低于对照组（P<0.05）。手术结束时,两组患者的血流动力学指标均较麻醉诱导时有不同程度上升（P<0.05）,血清IL-1β、HMGB1水平也有不同程度上升（P<0.05）;且观察组患者各项血流动力学指标明显低于对照组（P<0.05）,血清IL-1β、HMGB1水平也明显低于对照组（P<0.05）。观察组患者的睁眼时间、呼吸恢复时间、拔管时间明显短于对照组（P<0.05）。两组药品不良反应发生率比较差异无统计学意义（P>0.05）。结论:右美托咪定诱导老年患者深度麻醉能使HMGB1、血流动力学指标处于较为稳定的状态,减少七氟烷用量,确保手术能顺利进行。     

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.     

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.     

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.