右美托咪定用于眼科玻璃体手术镇静效果观察

摘 要 目的：在麻醉深度指数（CSI）指导下,评价眼科玻璃体手术中右美托咪定镇静的有效性和安全性。方法：采用前瞻性随机双盲对照试验方法,60例择期行玻璃体手术患者随机分为右美托咪定组（D组,右美托咪定以0.25 μg·kg-1·h-1输注）和咪达唑仑组（M组,咪达唑仑以25 μg·kg-1·h-1输注）。患者入手术室后行常规麻醉监测和CSI监测,术中CSI靶目标值设定为＞80。术中根据CSI值调整药物输注速率。记录术中循环、呼吸参数,术后对患者行镇痛评分、记录不良反应、评估患者和手术医生满意度。结果：D组患者手术开始35~50 min和术毕心率均低于M组（P＜0.05）,疼痛评分显著低于M组（P＜0.05）;两组患者其他血流动力学和呼吸参数、手术满意度和药品不良反应发生率比较,差异无统计学意义（P＞0.05）。 结论：右美托咪定在玻璃体手术中可降低心率,镇痛起效快,且不良反应小,适于该类手术镇静。     

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。     

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。     

体外培育牛黄联合氟哌啶醇治疗大鼠精神分裂症的研究

摘 要 目的：研究体外培育牛黄（CBS）联合氟哌啶醇对精神分裂症模型大鼠行为学的影响并探索其作用机制。方法: 以地卓西平马来酸盐（MK 801）制备大鼠精神分裂症模型。SD大鼠随机分为对照组,模型组,氟哌啶醇组（1.4 mg·kg-1）,氟哌啶醇联合CBS低剂量（50 mg·kg-1）、中剂量（100 mg·kg-1）、高剂量（150 mg·kg-1）组,CBS低剂量（50 mg·kg-1）、中剂量（100 mg·kg-1）、高剂量（150 mg·kg-1）组。用高架十字实验评价各组大鼠焦虑水平的影响,Western blot检测各组大鼠前额皮层c Fos蛋白水平。结果: 高架十字实验结果显示,氟哌啶醇组和联合用药组大鼠开臂次数百分比相比模型组明显增加（P<0.01）,而CBS各剂量组与模型组无显著差异。联合用药中、高剂量组开臂时间百分比显著大于氟哌啶醇组（P<0.05）。CBS和氟哌啶醇均可降低大脑前额皮层中c Fos蛋白含量（P<0.05或P<0.01）;而联合用药各剂量组较氟哌啶醇组c Fos蛋白含量均显著降低（P<0.05）。结论: 通过行为学评价发现,CBS与氟哌啶醇联合使用能协同降低大鼠精神分裂症模型中增高的焦虑水平,这可能与协同降低前额皮层c Fos蛋白含量有关。本研究为临床上两药的联合使用提供了药效学基础,具有一定的参考意义。     

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。     

丹酚酸B对肾病综合征大鼠的改善作用

摘 要 目的：研究丹酚酸B对多柔比星致肾病综合征（NS）模型大鼠的改善作用。方法: 采用一次性尾静脉注射多柔比星制备NS模型,造模成功后给予大鼠丹酚酸B（0.2 g·kg-1、0.1 g·kg-1）连续灌胃5周,以醋酸泼尼松为阳性对照,探讨丹酚酸B对NS大鼠的肾脏指数、24 h尿量、24 h尿蛋白含量、腹水量及尿中钠、钾、氯离子的影响;以及对NS大鼠肾脏组织的影响。结果: 与模型组比较,丹酚酸B高剂量能显著提高NS模型大鼠的24h尿量和尿钠含量（P＜0.05）,降低24 h尿蛋白含量、腹水量和肾脏指数（P<0.05或P<0.01）,且上述指标与阳性药比较无差异（P>0.05）甚至更优（P<0.05）。对大鼠血钠、尿钾、尿氯等指标无影响（P>0.05）。丹酚酸B高剂量降低大鼠腹水含量的作用明显优于低剂量（P<0.01）,其他指标高低剂量组比较,差异无统计学意义（P>0.05）。丹酚酸B可改善NS模型大鼠肾小管蛋白管型。结论: 丹酚酸B具有提高NS大鼠尿量,尿钠排泄,降低尿蛋白,腹水含量及改善肾脏损害的作用。     

一种中草药组方对裸鼠皮肤衰老的影响研究

摘 要 目的：考察一种中草药组方对D 半乳糖联合紫外线（UV）光照诱导衰老模型裸鼠皮肤的影响。方法: 每日皮下注射D 半乳糖1 000 mg·kg-1·d-1联合350 ~ 400 nm UV持续照射40 min,连续40 d,诱导亚急性衰老模型。雄性裸鼠随机分为正常对照组,模型组,中草药组方制剂低剂量组（4.16 ml·kg-1）、中剂量组（8.33 ml·kg-1）、高剂量组（16.66 ml·kg-1）,阳性对照组（纽崔莱润妍饮品8.33 ml·kg-1）,每组10只。于造模第11天分别灌胃给药30 d。检测血清中透明质酸,皮肤中透明质酸、羟脯氨酸、总胶原蛋白、Ⅲ型胶原蛋白、弹性蛋白的含量以及皮肤含水量;HE染色观察皮肤形态学改变。结果: 与模型组比较,中草药组方制剂中剂量组皮肤透明质酸含量显著增加（P <0.05）,高剂量组各项生化指标指标均有显著改善（P <0.05或P<0.01）;中、高剂量组各项指标与阳性对照组基本相当（P＞0.05,且低、中、高剂量组间无明显差异（P＞0.05））。中草药组方制剂中、高剂量组皮肤含水量显著增加（P <0.01）,与阳性对照组相当（P＞0.05）;低剂量组含水量明显低于高剂量组与阳性对照组（P＞0.05）。中草药组方制剂中、高剂量组与阳性对照组裸鼠。衰老皮肤的形态明显改善。结论: 该中草药组方具有一定的体内抗皮肤衰老作用。     

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.

     

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.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.