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。     

HPLC法测定美司钠原料中的有关物质

摘 要 目的：建立HPLC法测定美司钠原料中的有关物质。 方法: 采用C18柱（250 mm×4.6 mm,5 μm）;以甲醇 磷酸盐缓冲液（取磷酸二氢钾2.94 g、磷酸氢二钾2.94 g、四丁基硫酸氢铵2.6 g溶于660 ml水中,用磷酸调pH 2.3）（34∶66）为流动相;流速为1.0 ml·min-1;检测波长为235 nm。 结果: 美司钠与各杂质及强制破坏产物能完全分离;美司钠及杂质A、B、D、F分别在41.03～4 103.00 μg ·ml-1（r=1.000 0）、0.53～53.44 μg ·ml-1（r=1.000 0）、0.43～42.88 μg ·ml-1（r=1.000 0）、30.80～308.00 μg ·ml-1（r=1.000 0）、0.422 4～42.24 μg ·ml-1（r=1.000 0）范围内线性关系良好;各杂质加样回收率在97.8%～101.4%之间;进样精密度和重复性均符合规定;其中杂质A、B、F的相对校正因子分别为0.03,0.01,0.01。 结论: 建立的方法可用于美司钠原料有关物质的质量控制。     

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.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.