LncRNA GAS5通过miR-21调控脊髓损伤后神经细胞凋亡的机制研究

目的 明确长链非编码RNA生长阻滞特异性转录因子5（LncRNA GAS5）与微小RNA-21（miR-21）的关系,阐明LncRNA GAS5调控miR-21参与脊髓损伤后神经细胞凋亡的机制。方法 建立脊髓损伤大鼠和氧糖剥夺复氧（OGD/R）处理的大鼠肾上腺嗜铬细胞瘤细胞（PC-12）模型;沉默和过表达GAS5,构建下调shGAS5表达的慢病毒,通过生物信息学分析预测LncRNA GAS5与miR-21存在结合位点等。通过双荧光素酶报告基因实验等探究GAS5与miR-21的结合位点;采用实时荧光定量聚合酶链式反应（RT-qPCR）检测miR-21、GAS5、同源性磷酸酶-张力蛋白（phosphatase and tensin homolog,PTEN）基因、半胱天冬氨酸蛋白酶3（Caspase 3）、B淋巴细胞瘤（Bcl）-2相关X基因（Bax）、Bcl-2和蛋白激酶B（AKT）的RNA表达水平;Western blot检测Cleaved caspase 3、Bax、Bcl-2、AKT和磷酸化AKT（p-AKT）的蛋白表达水平;TUNEL技术检测神经细胞凋亡程度。结果 大鼠脊髓损伤后脊髓中miR-21、Bcl-2及p-AKT表达水平降低（P＜0.05）,GAS5、PTEN、Bax及Cleaved caspase-3表达均升高（P＜0.05）。PC-12体外培养与OGD/R损伤后出现与大鼠脊髓损伤模型类似结果,且于OGD/R处理后2 h最显著。GAS5可通过碱基互补配对方式结合miR-21,进而调控下游PTEN信号通路。下调GAS5或过表达miR-21可抑制PC-12细胞凋亡（P＜0.05）。结论 GAS5通过结合miR-21,上调PTEN并抑制AKT磷酸化,进而促进脊髓损伤诱导的神经细胞凋亡。     

小鼠神经细胞氧糖剥夺-复糖复氧时miR-93-5p与线粒体融合蛋白2的关系

目的评价小鼠神经细胞氧糖剥夺-复糖复氧时微小RNA-93-5p(miR-93-5p)与线粒体融合蛋白2(Mfn2)的关系。方法体外培养小鼠神经母细胞瘤细胞至对数生长期。实验Ⅰ采用随机数字表法将细胞分为5组(n=20):对照组(C组)、氧糖剥夺-复糖复氧组(OGD/R组)、miR-93-5p抑制剂组(I组)、siRNA-Mfn2+miR-93-5p抑制剂组(siMfn2+I组)和miR-93-5p阴性对照组(NC组)。氧糖剥夺:在低糖平衡盐溶液、37 ℃ 5%CO2-95%N2的环境中培养3 h, 复糖复氧:在正常培养基、37 ℃ 5%CO2-95%空气中复氧24 h。I组、siMfn2+I组与NC组在模型制备前48 h分别转染miR-93-5p抑制剂、miR-93-5p抑制剂+siRNA-Mfn2及阴性对照miRNA。采用CCK-8法检测细胞活力, 流式细胞术检测细胞凋亡率, qRT-PCR法检测miR-93-5p、Mfn2 mRNA表达水平, Western blot法检测Mfn2表达水平。实验Ⅱ构建野生型(WT)-Mfn2和突变型(MUT)-Mfn2质粒, 并分别与miR-93-5...     

长链非编码RNA PVT1通过调控miR-455的表达影响糖尿病肾病足细胞损伤和凋亡

目的:探究长链非编码RNA(lncRNA) PVT1通过调控miR-455对糖尿病肾病足细胞损伤和凋亡的影响。方法:采用高糖刺激永生化小鼠足细胞建立糖尿病肾病足细胞损伤模型,实验分为正常糖(NG)组:5.6 mmol/L葡萄糖,高糖(HG)组:30 mmol/L葡萄糖,高糖+转染对照(HG+si-NC)组:30 mmol/L葡萄糖+siRNA control,高糖+转染(HG+siPVT1)组:30 mmol/L葡萄糖+PVT1 siRNA。各组足细胞处理48 h后采用qRT-PCR检测细胞中PVT1和的miR-455的表达水平,荧光素酶报告实验检测PVT1和miR-455的靶向关系,Western blot检测足细胞标记蛋白Nephrin、WT-1和损伤因子Desmin的表达水平,流式细胞术检测足细胞凋亡情况。结果:与NG组相比,HG组足细胞中PVT1的表达明显升高,miR-455的表达水平明显降低,Nephrin、WT-1蛋白表达明显下调,Desmin蛋白表达明显上调,足细胞凋亡率明显升高,差异均有统计学意义(P 0.05);与HG组相比,HG+si-PVT1组足细胞中PVT1的表达水平明显降低,miR-455的表达水平明显升高,Nephrin、WT-1蛋白表达明显上调,Desmin蛋白表达明显下调,足细胞凋亡率明显降低,差异均有统计学意义(P 0.05)。荧光素酶报告实验结果表明PVT1能够靶向调控miR-455。结论:敲低PVT1可通过上调miR-455的表达抑制高糖诱导的足细胞损伤和凋亡。     

miR-567在胰腺癌细胞中的表达及其作用机制

目的:探讨miR-567在胰腺癌细胞中的表达及其作用。方法:采用qRT-PCR检测正常胰腺导管上皮细胞系HPDE6-C7及胰腺癌细胞系Panc-1、AsPC-1、HPAC、BxPC-3中miR-567表达。Panc-1细胞转染miR-567过表达慢病毒载体后,分别用CCK-8法、流式细胞术、划痕愈合实验、qRT-PCR、Western blot法检测细胞增殖、凋亡及迁移能力,以及KPNA4 mRNA与蛋白的表达、凋亡相关蛋白表达的变化。结果:miR-567在胰腺癌细胞系Panc-1、AsPC-1、HPAC、BxPC-3中的表达水平均明显低于正常胰腺导管上皮细胞系HPDE6-C7(均P0.05);miR-567慢病毒转染Panc-1细胞后,增殖能力明显减弱,凋亡率明显增加,划痕愈合率明显降低、KPNA4 mRNA与蛋白表达明显下调、而caspase-3及Bax蛋白表达明显上调(均P0.05)。结论:miR-567在胰腺癌细胞中表达降低,升高其表达可抑制胰腺癌细胞的生长与迁移能力,其机制可能与下调KPNA4并上调凋亡相关蛋白表达有关。     

七氟醚预处理对缺氧诱导因子1α表达和Slit2/Robo1信号通路的影响

目的评价七氟醚预处理对原代大鼠皮质神经元氧糖剥夺-复糖复氧后缺氧诱导因子(HIF)1α表达和Slit2/Robo1信号通路的影响。方法出生24h内的SD大鼠体外提取原代皮质神经元,以1×106/ml的密度接种于6孔板(2ml/孔)培养皿,采用随机数字表法分为四组:对照组(C组)神经元正常培养;氧糖剥夺-复糖复氧组(O组)神经元行氧糖剥夺90min;七氟醚预处理组(S组)在行氧糖剥夺前预先给予2%七氟醚处理1h,余同O组;HIF-1α抑制组(H组)在七氟醚预处理前行2ME(5μM/L)处理72h,余同S组。复糖复氧24h后收集神经元,采用Hoechst/PI双染色法测定神经元凋亡率;采用RT-PCR法测定HIF-1α、Slit2和Robo1mRNA的表达量;采用Western blot法测定HIF-1α、Slit2和Robo1蛋白的表达量。结果与C组比较,O组神经元PI阳性率明显升高,HIF-1αmRNA和蛋白表达量明显上调,Slit2和Robo1mRNA和蛋白表达量明显上调(P0.05);与O组比较,S组神经元PI阳性率明显下降,HIF-1αmRNA和蛋白表达量明显上调,Slit2和Robo1mRNA和蛋白表达量明显上调(P0.05);与S组比较,H组神经元PI阳性率明显升高,HIF-1αmRNA和蛋白表达量明显下调,Slit2和Robo1 mRNA和蛋白表达量明显下调(P0.05)。结论七氟醚预处理通过HIF-1α增加Slit2/Robol信号通路的表达,抑制原代大鼠皮质神经元在氧糖剥夺-复糖复氧后的凋亡。     

miR-133a对滋养层细胞系HTR8-SVneo的粘附及侵袭功能的影响

目的研究体外上调及下调miR-133a对滋养层细胞系HTR8-SVneo的粘附及侵袭功能的影响。方法将培养的HTR8-SVneo细胞根据脂质体转染因素分为对照组(转染空质粒)、上调组(转染mimics)、下调组(转染inhibitor),通过荧光定量PCR法检测各组miR-133a的表达水平,采用MTT法检测细胞粘附能力的变化,同时运用Transwell实验观察细胞侵袭能力的变化。结果与对照组比较,miR-133a上调组细胞黏附能力显著下降,miR-133a下调组细胞黏附力显著升高(P均0.05);与对照组比较,miR-133a上调组细胞侵袭力显著降低,miR-133a下调组细胞侵袭力显著升高(P均0.01)。结论 miR-133a在调控滋养层细胞粘附能力和侵袭能力方面起着重要作用。     

基质交联分子1对前列腺癌PC-3细胞凋亡相关蛋白表达的影响

目的:观察抑制基质交联分子1(STIM1)对前列腺癌PC-3细胞凋亡相关蛋白表达的影响。方法:将携带STIM1基因的小干扰RNA(shRNA)慢病毒载体STIM1-pGCSIL-GFP转染人激素非依赖性前列腺癌PC-3细胞,3d后荧光倒置显微镜观察转染效率;1周后RT-PCR及Western印迹验证STIM1抑制表达有效性,并采用Western印迹检测PC-3细胞中凋亡相关蛋白Bcl-2、Bax,survivin、激活型Caspase-3的表达水平。结果:倒置显微镜观察发现PC-3细胞病毒转染效率80%。转染1周后,RT-PCR及Western印迹显示STIM1被有效抑制。抑制STIM1表达后,对照组Bcl-2/Bax比率为1.24,干扰组PC-3细胞Bcl-2/Bax比率为0.31,比率显著下降;干扰组PC-3细胞survivin表达明显降低,相对表达量为对照组的0.14倍;Caspase-3裂解激活相对表达量为对照组的1.52倍(P0.05)。结论:STIM1在前列腺癌PC-3细胞中可视为致癌基因,抑制其表达可通过下调Bcl-2/Bax比率,降低survivin表达,激活Caspase-3级联通路,诱导细胞凋亡。     

miR-520激活内质网应激导致滋养细胞凋亡的相关研究

目的探讨miR-520通过激活内质网应激导致滋养细胞凋亡,从而参与复发性流产(RSA)的作用机制。方法利用miR-520慢病毒(实验组)和空载慢病毒(对照组)分别感染人滋养细胞系HTR8细胞,并用嘌呤霉素筛选出稳转株。以未感染细胞为空白对照,利用流式细胞术及荧光显微镜观察确定病毒转染效率、实时荧光定量PCR(qRT-PCR)检测各组细胞miR-520的表达水平;通过CCK-8法测定细胞增殖能力、流式细胞术分析细胞凋亡率、乳酸脱氢酶(LDH)试剂盒检测细胞损伤程度、Mito-Tracker Red CMXRos试剂盒检测线粒体膜电位变化;通过Western blot检测凋亡通路中cleaved Caspase-3、cleaved Caspase-9以及cleaved Caspase-12水平的变化,同时检测内质网应激相关蛋白CHOP、葡萄糖调节蛋白GRP78的水平变化。结果与对照组比较,miR-520在人滋养细胞系HTR8细胞中过表达后,HTR8细胞增殖能力显著下降(P0.05),LDH活性升高(P0.05),HTR8细胞线粒体膜电位降低(P0.05),细胞凋亡数显著增加(P0.05);凋亡相关蛋白cleaved Caspase-3、cleaved Caspase-9以及cleaved Caspase-12水平均有不同程度的增高(P0.05),同时内质网应激相关蛋白CHOP、GRP78表达水平上调(P0.05)。结论 miR-520可能通过激活内质网应激诱导HTR8细胞发生凋亡,从而参与RSA的发生。     

Nrf2/NLRP3信号通路在丙泊酚后处理减轻氧糖剥夺-复糖复氧大鼠海马神经元损伤中的作用

目的评价核因子E2相关因子2/核苷酸结合寡聚化结构域样受体蛋白3(Nrf2/NLRP3)信号通路在丙泊酚后处理减轻氧糖剥夺-复糖复氧大鼠海马神经元损伤中的作用。方法原代培养孕16～18 d Wistar大鼠胎鼠海马神经元7 d, 采用随机数字表法分为4组(n=42):对照组(C组)正常培养;氧糖剥夺-复糖复氧组(O组)氧糖剥夺1 h后复糖复氧;丙泊酚后处理组(P组)复糖复氧即刻加入丙泊酚(终浓度1.2 μg/ml)孵育2 h, 更换为正常培养液;Nrf2 siRNA(-)转染组(N组)原代神经元培养第3天行携带Nrf2基因敲除的慢病毒转染, 24 h后更换为正常培养液, 第7天进行模型制备及丙泊酚后处理。于继续培养24 h时收集细胞, 采用流式细胞术检测神经元凋亡率, RT-PCR法检测Nrf2和NLRP3 mRNA表达, Western blot法检测Nrf2和NLRP3表达, ELISA法测定TNF-α、IL-6和IL-1β浓度;试剂盒法检测还原性谷胱甘肽(GSH)、SOD和过氧化氢酶(CAT)活性。结果与C组比较, O组和P组神经元凋亡率升高, TNF-α、IL-6和IL-1β浓...     

MiR-125通过调控P38-Sirt1-P53信号通路参与高糖诱导的足细胞损伤

目的:探讨高糖条件下miR-125表达下调,通过激活P38-SIRT1-P53通路导致足细胞损伤的分子机制。方法:体外实验观察不同条件刺激下的足细胞的凋亡情况,miR-125以及P38-SIRT1-P53表达情况。结果:(1)高糖可以诱导体外足细胞中miR-125表达下调并导致足细胞凋亡发生,足细胞转染miR-125可以抑制高糖所诱导的足细胞凋亡。(2)通过双荧光素酶报告系统,我们证实P38是miR-125的靶基因,高糖条件下的足细胞miR-125表达下调导致P38蛋白以及磷酸化P38蛋白表达上调从而激活SIRT1-P53通路。(3)miR-125高表达以及P38特异性拮抗剂均可以阻断高糖所诱导的SIRT1-P53通路活化,从而抑制足细胞凋亡发生。结论:高糖诱导足细胞的凋亡,其机制可能与miR-125下调介导的P38-SIRT1-P53通路激活有关。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.