右美托咪定对失血性休克大鼠肠黏膜的保护作用

摘 要 目的：观察右美托咪定预处理对失血性休克大鼠肠黏膜的保护作用及其可能机制。 方法: 32只SD大鼠随机分为4组：对照（Control）组、失血性休克（HS）组,右美托咪定低（Dex1,5 μg·kg-1）、高（Dex2,10 μg·kg-1）剂量组。Control组和HS组通过尾静脉在20 min内用微量泵注0.5 ml生理盐水,Dex1和Dex2组给予0.5 ml包含相应剂量右美托咪定稀释液。30 min之后,除Control组外,其余3组建立失血性休克大鼠模型。检测大鼠肠黏膜中超氧化物歧化酶（SOD）、丙二醛（MDA）、一氧化氮（NO）、钙离子（Ca2+）的含量、pH（pHi）及细胞凋亡率,并观察肠黏膜组织病理学改变。 结果: 与HS组比较, 右美托咪定各剂量预处理组均显著降低MDA、NO、Ca2+含量、细胞凋亡率及组织病理学评分,显著增加SOD含量和pHi（P<0.05）;但不同剂量组间差异无统计学意义（P＞0.05）。结论: 右美托咪定预处理对缺血再灌注大鼠对肠黏膜具有保护作用,其潜在作用机制可能与改善肠黏膜的抗氧化功能有关。     

不同剂量右美托咪定用于心房颤动经导管射频消融术中的疗效

摘 要 目的：探讨不同负荷剂量右美托咪定用于心房颤动经导管射频消融术中的临床疗效和安全性。方法: 接受导管射频消融手术的房颤患者63例随机分为3组,分别接受大负荷剂量的右美托咪定1 μg·kg^-1（HDex组）,小负荷剂量的右美托咪定0.5 μg·kg^-1（LDex组）和等量0.9%氯化钠注射液（NS组）,均静脉输注10 min。HDex组与LDex组负荷剂量后予维持剂量右美托咪定0.4 μg·kg^-1·h-1至手术结束,NS组予等量0.9%氯化钠注射液。3组患者在手术开始时均予局部麻醉,静脉联合泵注芬太尼（1 μg·kg^-1·h-1）至手术结束。记录3组入室时(T0)、给负荷量后(T1)、手术开始时(T2)、射频消融开始后10 min(T3)、射频消融结束后10 min(T4)的收缩压（SBP）、舒张压（DBP）、心率（HR）、Ramsay镇静评分。记录术中面罩辅助通气发生次数、因疼痛需调整芬太尼用量而中断手术次数、手术时间。结果: T1、T2、T3、T4时,HDex组、LDex组Ramsay镇静评分收缩压、舒张压、心率与NS组比较差异有统计学意义（P<0.05）。在T1时,HDex比LDex组收缩压、舒张压、心率下降更显著（P<0.05）。HDex组发生2例心动过缓,2例术中面罩辅助通气。NS组发生2例因疼痛调整芬太尼用量而中断手术。结论: 在与芬太尼联用时,临床上予0.5 μg·kg^-1小负荷剂量的右美托咪定即可满足心房颤动经导管射频消融术的镇静、镇痛需要,且不良反应少。     

右美托咪啶复合麻醉对硬膜外血肿清除术患者脑保护效应

摘 要 目的:观察右美托咪啶复合麻醉对颅内硬膜外血肿清除术对患者的脑保护效应。方法：硬膜外血肿手术患者60例随机分成两组,分别给予丙泊酚复合麻醉和右美托咪啶复合麻醉,比较两组患者手术前后的神经功能、血清学指标及药品不良反应发生情况。结果：观察组患者术后24 h格拉斯哥昏迷评分(GCS评分)明显高于对照组(P<0.05),术后24 h的血清神经元特异性烯醇化酶（NSE）和内皮素（ET）水平均明显低于对照组(P<0.05);观察组患者药品不良反应发生率明显低于对照组（P<0.05）。结论：硬膜外血肿清除术患者采用右美托咪定复合麻醉,术后GCS评分与血清NSE、ET水平均明显优于采用丙泊酚复合麻醉的患者,且不良反应明显较少,提示右美托咪定复合麻醉对患者的脑保护效应更佳,且安全性高。     

右美托咪定与丙泊酚联用于老年患者无痛胃镜麻醉的临床观察

摘 要 目的： 观察右美托咪定与丙泊酚联用在老年患者无痛胃镜麻醉中的效果及安全性。方法: 拟行无痛胃镜检查的老年患者70例随机分为观察组（35例）和对照组（35例）;观察组给予右美托咪定联合丙泊酚麻醉,对照组给予丙泊酚麻醉。比较两组患者的麻醉诱导时间、苏醒时间,患者不同时点的生命体征,术中并发症、药品不良反应等指标。结果: 观察组麻醉诱导时间、苏醒时间均短于对照组（P<0.01）。两组患者平均动脉压（MAP）在T2、T3、T4阶段均明显低于T1阶段（P<0.05或P<0.01）;对照组的HR在T3阶段、R在T2阶段均低于T1阶段（P<0.05）;观察组的RR在T2阶段明显低于T1阶段（P<0.05）;观察组MAP在T2、T3阶段明显高于对照组（P<0.01）,在T4阶段低于对照组（P<0.05）;观察组的HR在T3阶段明显高于对照组（P<0.05）。观察组患者术中并发症显著低于对照组（P<0.05）。结论:右美托咪定联合丙泊酚的麻醉效果与安全性均高于单用丙泊酚,值得临床推广应用。     

右美托咪啶联合磷酸肌酸钠防治老年患者全麻术后谵妄效果

摘 要 目的:观察右美托咪啶、磷酸肌酸钠单独和联合应用对老年患者全身麻醉术后谵妄的防治效果。方法: 择期阴式子宫切除+阴道前后壁修补术全身麻醉老年患者60例,随机双盲均分为四组,即0.9%氯化钠注射液空白对照组（C组）、右美托咪啶组（D组）、磷酸肌酸钠组（CP组）和右美托咪啶联合磷酸肌酸钠组（DCP组）,各组麻醉前给予对应药物。监测围术期呼吸循环变化,术前第1天行MMSE评分,术后第1天行MMSE评分和视觉模拟疼痛评分,并且进行术后谵妄的诊断。结果:C组和CP组患者在气管插管后即刻HR和MAP显著上升,且明显高于入室时值和D组或DCP组对应值（P＜0.05或0.01）;术中SpO₂,PetCO2₂,以及术后VAS评分差异无统计学意义（P＞0.05）;C组、D组、CP组患者MMSE评分较术前均有显著降低（P＜0.05或0.01）,D组、CP组、DCP组患者术前术后MMSE差值均显著低于C组（P＜0.05或0.01）,术后DCP组患者MMSE评分显著高于C组（P＜0.01）;D组、CP组、DCP组患者谵妄发生率均显著低于C组（P＜0.05或0.01）,且DCP组患者谵妄发生率显著低于D组或CP组（P＜0.05）。结论: 全身麻醉前预防性应用右美托咪啶和（或）磷酸肌酸钠,可以有效地降低老年患者术后谵妄的发生率,尤其是两种药物联合应用时。     

右美托咪定对体外循环下全身炎症反应综合征的保护效果观察

摘 要 目的：观察右美托咪定(DEX)对体外循环（CPB）下患者全身炎症反应综合征（SIRS）的保护效果。方法: 择期体外循环下行心脏二尖瓣置换术的患者62例,随机分为DEX组和对照组各31例。DEX组恒速输注DEX 0.5μg·kg-1·h-1,对照组恒速输注等量0.9%氯化钠注射液。其余麻醉用药两组相同。分别于麻醉诱导前(T0)、主动脉开放后10 min(T1)、停机时(T2)、停机后4 h(T3)、停机后12 h(T4)和停机后24 h(T5)监测两组患者血清炎性细胞因子C反应蛋白(CRP)、肿瘤坏死因子（TNF） α、白细胞介素（IL） 6、IL 8、IL 10的水平以及患者生命体征, 比较两组患者术后机械通气时间、ICU观察时间、术后24h发生SIRS例数及住院天数。结果: T1～T5时两组患者血清CRP明显升高(P<0.05);T3～T5时DEX组CRP明显低于对照组(P<0.05)。T2～T4时对照组血清TNF α明显升高(P<0.05),T2、T3时DEX组血清TNF α明显升高(P<0.05);T3、T4时DEX组血清TNF α低于对照组(P<0.05)。T2～T5时两组血清IL 6明显升高(P<0.05),T1～T5时两组血清IL 8明显升高(P<0.05),T1～T3时两组血清IL 10明显升高(P<0.05);T2～T4时DEX组IL 6、IL 8低于对照组(P<0.05),T1～T3时DEX组IL 10高于对照组(P<0.05)。T3～T5时两组患者WBC均较T0时显著升高(P<0.05),且对照组WBC高于同期DEX组(P<0.05)。两组患者术后机械通气时间、ICU观察时间、术后24 h内诊断SIRS例数、住院天数、药品不良反应发生例数等比较,差异无统计学意义（P>0.05）。结论: CPB期间持续输注右美托咪定能降低患者血清炎性细胞因子水平,一定程度减轻全身炎症反应。     

经腹子宫全切术患者不同剂量右美托咪啶硬膜外麻醉镇静效果观察

摘 要 目的： 观察不同剂量右美托咪啶在硬膜外麻醉经腹子宫全切术中的镇静效果和安全性。方法: 硬膜外麻醉经腹子宫全切术择期患者120例随机分为4组,即不同剂量右美托咪啶镇静组（D1组,D2组,D3组）和咪达唑仑镇静组（M组）。D1组、D2组、D3组在手术前10 min静脉泵注右美托咪啶0.5μg·kg^-1,随之分别以0.4,0.6,0.8 μg·(kg·h)^-1维持输注;M组患者在手术前10 min静脉泵注咪达唑仑0.06 mg·kg^-1,随之以0.04 mg·(kg·h)^-1维持输注。比较各组患者入室时（T0）、确定硬膜外麻醉阻滞效果满意时（T1）、镇静药物泵注后10 min（T2）、20 min（T3）、40 min（T4）、手术结束时（T5）的平均动脉压（MAP）、心率（HR）、呼吸频率（RR）和血氧饱和度（SpO₂）,以及镇静药物使用时间和手术时间。评估各时点镇静程度,及术后患者手术期间遗忘程度、药品不良反应和麻醉服务满意度。结果:T3时点后,D3组HR显著低于其余3组（P＜0.05）;T2时点后,4组HR均明显低于T0时（P＜0.05和P＜0.01）。M组T3、T4 时点RR显著低于其余3组（P＜0.05）。与T0时比较,T2时点后,各组患者均取得显著镇静效果（P＜0.05和P＜0.01）;D3组T3、T4时镇静评分显著优于D1组和M组（P＜0.05）。4组患者均未出现明显药品不良反应。结论: 硬膜外麻醉经腹子宫全切术应用右美托咪啶维持镇静无类似输注咪达唑仑后发生呼吸抑制的风险,但剂量宜低于0.8 μg·(kg·h)^-1。     

右美托咪定对高氧诱导急性肺损伤小鼠的保护作用及Nrf2/HO-1通路的影响

摘 要 目的：探讨右美托咪定对高氧诱导急性肺损伤小鼠的保护作用及核转录因子红细胞系2p45相关因子2（Nrf2）/血红素加氧酶 1（HO-1）通路的影响。 方法: 将100只C57BL/6小鼠随机分为5组：正常对照组、模型组、地塞米松组（100 mg·kg-1）、右美托咪定低（40 mg·kg-1）、高（80 mg·kg-1）剂量组。除正常对照组外,其余各组建立高氧诱导急性肺损伤模型,并于造模成功后腹腔注射相应药物,正常对照组和模型组给予等体积生理盐水,qd,持续7 d。实验结束后,检测小鼠肺/体比值、肺损伤评分、血氧分压（PaO2）,小鼠肺组织中Nrf2、HO-1 mRNA及蛋白表达水平,胱天蛋白酶 1（caspase 1）、白细胞介素 1β（IL 1β）、白细胞介素 18（IL 18 ）蛋白水平。制作肺部HE染色切片,观察肺损伤情况。 结果: 与正常对照组比较,模型组肺/体比值、肺损伤评分、Nrf2 mRNA及蛋白表达水平、IL 1β、IL 18、caspase 1蛋白表达水平明显升高,PaO2、HO-1 mRNA及蛋白表达水平明显降低（P<0.05）;与模型组比较,右美托咪定组肺/体比值、肺损伤评分、Nrf2 mRNA及蛋白表达水平、IL 1β、IL 18、caspase 1蛋白表达水平明显降低,PaO2、HO-1 mRNA及蛋白表达水平明显升高（P<0.05）,且呈剂量相关性;右美托咪定低剂量组与地塞米松组比较差异有统计学意义（P<0.05）。正常对照组肺泡组织结构正常,无炎症细胞浸润、无胶原蛋白沉淀;模型组、右美托咪定低剂量组肺泡壁明显增厚、破裂,可见中性细胞及少量嗜酸性细胞浸润,肺间质可见较多胶原蛋白沉淀;右美托咪定高剂量组及地塞米松组肺泡结构基本正常,有少量中性细胞侵润,几乎无胶原蛋白沉淀。 结论: 右美托咪定对高氧诱导急性肺损伤小鼠的保护作用与抑制Nrf2 mRNA及蛋白表达水平表达,进而抑制IL 1β、IL 18、caspase 1蛋白表达有关。     

腰丛神经阻滞和全身麻醉用于70岁以上患者全髋骨置换术的效果比较

摘 要 目的：比较利多卡因 罗哌卡因腰丛神经阻滞和丙泊酚 瑞芬太尼全身麻醉用于70岁以上患者全髋骨置换术的临床效果。方法: 58例≥70岁的择期全髋骨置换术患者,按手术时间先后依次分为A组（利多卡因 罗哌卡因腰丛神经阻滞复合右美托咪定麻醉）28例,B组（丙泊酚 瑞芬太尼全身麻醉）30例。评估比较两组患者围术期生命体征的稳定情况和术后麻醉恢复情况,术后24 h麻醉随访调查麻醉满意度。结果: A组患者手术期间生命体征各记录时间点值两两比较,差异均无统计学意义（P＞0.05）。B组患者诱导后及气管插管后血压或心率均较诱导前明显波动（P＜0.05）。B组患者围术期心血管药物使用例数显著多于A组患者（P＜0.01）。A组患者中,20例术后直接回病房,8例在麻醉恢复室观察0.5～1 h;B组12例术后控制呼吸直接回重症医学科病房, 7例拔除气管导管,回重症医学科病房;11例在麻醉恢复室观察1～2 h。与A组相比,B组患者术后发生精神障碍情况显著增加（P＜0.05）,同时麻醉满意度明显低于A组（P＜0.01）。结论: 适度剂量的利多卡因 罗哌卡因腰丛神经阻滞复合右美托咪定麻醉是高龄患者全髋骨置换术时一种合宜的麻醉选择。     

非体外循环冠状动脉旁路移植术患者右美托咪啶联合地佐辛术后镇痛效果及对心肌酶谱影响的回顾性分析

摘 要 目的：回顾性分析非体外循环冠状动脉旁路移植术（OPCABG）患者术后应用右美托咪啶联合地佐辛镇痛对心肌酶谱的影响,并评价其镇痛效果及不良反应情况。方法: 采用回顾性研究方法,收集择期全麻OPCABG患者58例,根据治疗方法分为两组。观察组29例术后予右美托咪啶联合地佐辛镇痛,对照组29例术后予地佐辛镇痛,其余治疗方案两组相同。比较分析两组术前及术后24 h的乳酸脱氢酶（LDH）、肌酸激酶（CK）及肌酸激酶同工酶（CK MB）的数值变化,监测麻醉前、拔管后不同时间点的收缩压（SBP）、舒张压（DBP）、心率（HR）、血氧饱和度（SpO2）的数据,对术后不同时间点的镇静程度进行评分,记录两组患者术后72 h不良反应情况。结果: 两组患者术后LDH、CK及CK MB水平均高于术前(P＜0.05);而观察组患者术后心肌酶水平均低于对照组(P＜0.05)。两组患者麻醉前、拔管后不同时间点（6,12,24,48,72 h）的SBP、DBP、HR和SpO2比较,差异无统计学意义(P＞0.05)。两组患者术后不同时间点（12,24,36,48,72 h）的Ramsay评分、VAS评分及术后24,48,72 h累计有效按压次数比较,差异无统计学意义(P＞0.05)。观察组患者恶心呕吐及躁动发生率明显低于对照组(P＜0.05)。结论: OPCABG患者术后应用右美托咪啶联合地佐辛能够保护心肌,增强镇痛效果,降低不良反应发生率。     

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.