TLR4、TBK/IRF3信号通路介导肾小管上皮细胞与单核细胞相互作用

目的:探讨单核细胞与肾小管上皮细胞相互作用的分子机制。方法:体外建立单核细胞(U937)与肾小管上皮细胞(HK-2)共培养系统,观察HK-2细胞对U937细胞Toll样受体4(toll-like receptors 4,TLR4)及TANK结合蛋白激酶(TBK)/干扰素调节因子3(IRF3)信号通路的影响;观察阻断TBK/IRF3信号通路对单核细胞分化的影响。结果:HK-2细胞促进U937细胞TLR4及TBK/IRF3信号通路蛋白及mRNA的表达(P0.05);阻断TBK/IRF3信号通路抑制HK-2细胞诱导U937细胞发生M1型转化(P0.05)。结论:TLR4分子介导HK-2细胞与U937细胞相互作用,激活TBK/IRF3信号通路,导致U937细胞发生M1型转化,进一步诱导炎症因子产生,促进肾脏纤维化。     

黄芪甲苷预处理对小鼠肝脏缺血再灌注损伤的保护作用

目的 探讨黄芪甲苷( astragalosideⅣ)预处理对小鼠肝脏缺血再灌注损伤的保护作用及其机制.方法 将60只雄性C57BL/6小鼠分为4组,15只/组,A组:假手术对照组,B组:假手术黄芪甲苷组,C组:实验对照组,D组:黄芪甲苷实验组.黄芪甲苷组每只腹腔注射黄芪甲苷24 mg·kg-1·d-1,对照组每天腹腔注射等体积无菌生理盐水,共1周.建立小鼠肝脏部分缺血再灌注损伤模型,复流24h后采集标本,测定血清中转氨酶ALT和AST水平,光镜下观察H＆E染色肝组织病理学变化,酶联免疫吸附试验(ELISA)检测血清中IL-1β,IL-6,TNF-α的含量,采用Western blot 技术检测小鼠肝脏组织中核因子-κB (NF-κB)的表达.结果 黄芪甲苷实验组ALT及AST较实验对照组明显降低[AST:C组(4290±292) U/L vs.D组(2373±416) U/L,t=0.844;ALT:C组(4146 ±500) U/L vs.D组(2318 ±289) U/L,t =7.08,均P＜0.05],组织学损伤也明显减轻;ELISA 结果显示,黄芪甲苷预处理能明显降低外周IL-1β,IL-6,TNF-α的含量(IL-1 β:t 10.04;IL-6:t6.281;TNF-α:t =6.817;均P＜0.05).黄芪甲苷实验组肝脏组织中NF-κB表达量明显低于实验对照组.结论 黄芪甲苷预处理对小鼠肝脏缺血再灌注损伤有明显的保护作用.     

黄芪甲苷对紫外线诱导皮肤成纤维细胞表达TGFβ RⅡ与Smad7的影响

目的：探讨黄芪甲苷对紫外线诱导皮肤成纤维细胞TGFβRⅡ、Smad7mRNA以及蛋白质表达的影响。方法：培养原代人皮肤成纤维细胞,UVA及UVB分别照射人成纤维细胞,黄芪甲苷进行干预,MTT法检测细胞增殖活性,以ELISA法检测Smad7的生成量,半定量RT-PCR法检测TGFβRⅡ、Smad7的mRNA表达,Western blot法检测TGFβRⅡ的蛋白表达。结果：不同浓度的黄芪甲苷干预组与正常对照组相比,成纤维细胞增殖活性随浓度增加而增强,药物浓度为40μg/ml时最显著（P〈0.05）;UV辐射组与正常组相比,细胞上清液中Smad7蛋白含量明显增高,细胞内TGFβRⅡ的mRNA和蛋白表达均下降,Smad7mRNA表达增强;黄芪甲苷干预后,细胞上清液中Smad7蛋白含量下降,细胞内TGFβRⅡ的mRNA以及蛋白表达水平明显增高,Smad7mRNA表达下降（P〈0.05）。结论：黄芪甲苷可能通过提高成纤维细胞的增殖活性,上调TGFβRⅡmRNA、蛋白水平以及下调Smad7mRNA、蛋白水平的表达来对抗紫外线抑制TGF-β/Smad信号通路的传导,缓解皮肤光老化进程。     

黄芪甲苷干预高糖诱导的足细胞转分化的体外研究

目的:观察黄芪甲苷对高糖诱导的足细胞转分化的影响。方法:将条件性永生的小鼠足细胞随机分为高糖组(HG)、正常对照组(NG)、甘露醇高渗对照组(MA)、及HG+不同剂量(5、15、30μg/ml)黄芪甲苷(AS-IV)干预组,采用免疫双标法、real time RT-PCR检测nephrin和desmin表达的变化。结果:高糖诱导足细胞转分化,desmin的表达增加,nephrin的表达减少。不同剂量黄芪甲苷可不同程度抑制高糖引起的上述改变。结论:高糖能诱导足细胞发生上皮-间充质转分化(EMT),黄芪甲苷能抑制高糖诱导的EMT。     

NF-κB通路在单核细胞诱导肾小管上皮细胞转分化中的作用

目的 观察单核细胞（U937细胞）对人近端肾小管上皮细胞（HK-2细胞）转分化的影响及其分子机制。 方法 将HK-2细胞与人单核细胞系U937细胞共培养;倒置相差显微镜观察HK-2细胞形态;Western印迹、实时荧光定量PCR法检测α平滑肌肌动蛋白（α-SMA）、纤连蛋白（FN）、E钙黏蛋白（E-cadherin）和胞间黏附分子1（ICAM-1）表达;BCECF-AM荧光染色法测定单核细胞黏附;流式细胞仪法检测HK-2细胞表面分子ICAM-1表达;基因芯片筛选HK-2细胞基因变化;利用信号阻断剂阻断基因芯片筛选出的信号通路,进一步验证单核细胞诱导肾小管上皮细胞转分化的分子机制。 结果 单核细胞可直接诱导HK-2细胞发生形态变化,减少HK-2细胞E-cadherin表达（均P < 0.05）,并上调α-SMA、FN表达（均P < 0.05）。应用CD18抗体阻断CD18-ICAM-1可抑制单核细胞黏附及其诱导的HK-2细胞形态变化。基因芯片结果显示,NF-κB信号通路分子CC亚族趋化因子配体20（CCL20）、白细胞介素（IL）2、IL-8、脂磷壁酸（LTA）及血小板内皮细胞黏附分子1（PECAM1）表达明显增加（均P < 0.05）。NF-κB信号阻断剂吡咯烷二硫氨基甲酸（PDTC）能显著抑制HK-2细胞形态变化及表面ICAM-1表达,抑制单核细胞诱导的肾小管上皮细胞转分化。 结论 单核细胞通过CD18分子与HK-2细胞表面ICAM-1结合,从而启动NF-κB信号通路介导的特定基因转录,最终导致肾小管上皮细胞发生转分化。     

红景天苷对缺氧肾小管上皮细胞Toll受体2、IL-6表达及其凋亡的影响

目的:观察红景天苷(salidroside Sal.)对氯化钴(cobaltous chloride,Co Cl2·6H2O)诱导的缺氧人肾小管上皮细胞(human kidney tubular epithelia cell,HKC)Toll样受体2(toll-like receptor 2,TLR-2)表达、白细胞介素-6(interleukin-6,IL-6)的分泌及细胞凋亡的影响。方法:HKC细胞置于六孔板培养,随机分为正常对照组、缺氧模型组、红景天苷(salidroside Sal.)干预组(25μg/ml、50μg/ml、100μg/ml)。其中缺氧模型采用300μmol/L氯化钴处理6 h得到,红景天苷干预组在此模型基础上再用不同浓度的红景天苷处理缺氧细胞24 h。RT-PCR和Western blot检测TLR-2的表达,ELISA检测各组细胞上清中IL-6含量,流式细胞仪检测缺氧HKC凋亡情况。结果:氯化钴诱导HKC TLR-2蛋白(P<0.05)及RNA表达上调(P<0.01)、IL-6分泌增加(P<0.01)及细胞凋亡增加(P<0.01)。25μg/ml和50μg/ml的红景天苷能降低缺氧HKC细胞IL-6的水平(P<0.01),50μg/ml红景天苷抑制作用强于25μg/ml(P<0.05)。与缺氧模型组比较,尽管100μg/ml红景天苷能降低缺氧HKC细胞IL-6的绝对值水平,但差异无统计学意义(P>0.05)。25μg/ml,50μg/ml和100μg/ml红景天苷均能抑制TLR-2蛋白表达(P<0.01),且100μg/ml较25μg/ml红景天苷抑制作用显著(P<0.05),但25μg/ml与50μg/ml、50μg/ml与100μg/ml红景天苷比较,它们抑制作用的强弱差异无统计学意义(P>0.05)。三种浓度的红景天苷也能抑制缺氧HKC TLR-2的RNA表达(P<0.01),50μg/ml及100μg/ml红景天苷抑制作用强于25μg/ml红景天苷(P<0.05),但50μg/ml与100μg/ml红景天苷比较,二者抑制作用差异无统计学意义(P>0.05)。50μg/ml和100μg/ml红景天苷能抑制缺氧HKC凋亡(P<0.01),但25μg/ml红景天苷未表现出抑制凋亡的作用(P>0.05),50μg/ml与100μg/ml红景天苷比较,两者抑制凋亡的作用差异无统计学意义(P>0.05)。结论:红景天苷对缺氧HKC的TLR-2蛋白及RNA表达、IL-6的分泌及细胞凋亡均有抑制作用,但其抑制效应呈现非剂量依赖性。     

肿瘤相关成纤维细胞培养液上清促进肿瘤细胞增殖和血管生成的研究

目的 探讨在体外实验条件下,肿瘤相关成纤维细胞如何通过旁分泌机制促进肿瘤细胞的增殖和血管生成.方法 分别提取原代卵巢癌相关成纤维细胞(TAFs)与正常卵巢相关成纤维细胞(N Fs)的培养液上清(CM);实验组为2ml TAFs-CM处理卵巢癌细胞(SKOV-3,1×105/孔),对照组为2 ml NFs-CM处理卵巢癌细胞(SKOV-3,1×105/孔),空白组为正常培养的卵巢癌细胞(SKOV-3,1×105个/孔),干预组为在实验组中加入20 μmol转化生长因子-β(TGF-β)特异性小分子抑制剂SB-431542(10 μmol/ml);应用流式细胞仪分析各组细胞生长周期;逆转录-聚合酶链反应(RT-PCR)法检测各组细胞增殖细胞核抗原(PCNA)、α-平滑肌肌动蛋白(α-SMA)、血管内皮生长因子(VEGF) mRNA的表达,Western blot法检测各组细胞TGF-β1、α-SMA、VEGF蛋白的表达.结果 实验组卵巢癌细胞增殖较对照组显著增加(细胞S期比例:实验组22.10±1.84比对照组12.77±1.43,P＜0.05);而加入SB431542干预后则可明显抑制促增殖作用(细胞S期比例:干预组12.33±1.12比实验组22.10±1.84,P＜0.05);RT-PCR提示实验组PCNA、α-SMA、VEGF mRNA较其他组表达显著上调(P＜0.05),Western blot结果提示实验组TGF-β1、α-SMA、VEGF蛋白表达亦显著上调(P＜0.05),在加入SB-431542后以上基因及蛋白的表达均受到抑制(P＜0.05).结论 卵巢癌相关成纤维细胞可以通过旁分泌机制促进卵巢癌细胞的增殖,并上调血管生成相关基因及蛋白的表达,而通过抑制TGF-β信号通路作用后则可以有效抑制这类作用.     

金雀异黄素在甲状旁腺激素诱导的人近曲小管上皮细胞结缔组织生长因子表达中的调控作用

目的 探讨金雀异黄素（Gen）对甲状旁腺激素（PTH）引起的人近曲小管上皮细胞分泌结缔组织生长因子（CTGF）的调控作用。 方法 应用实时定量-聚合酶链反应（real time-PCR）、Western蛋白印迹、报告基因等技术,观察Gen对PTH诱导人近端肾小管上皮细胞系HK-2细胞CTGF表达的影响。使用MAPK通路抑制剂U0126阻断信号通路以明确Gen发挥作用的机制。 结果 HK-2细胞有基础量的CTGF mRNA和蛋白表达,PTH刺激后其表达量显著增加（P ＜ 0.05）。10-10 mol/L PTH作用12 h后,荧光素酶活性较对照组明显升高（1.8884±0.0780比0.9891±0.0300,P ＜ 0.01）。Gen剂量依赖性下调PTH诱导的HK-2细胞CTGF表达。正常HK-2细胞有少量磷酸化（p）ERK1/2表达,PTH刺激后p-ERK1/2表达明显升高,以10-10 mol/L PTH作用30 min时效应最强。U0126作用后,CTGF mRNA、蛋白表达均明显下降（P ＜ 0.05）。Gen抑制PTH所致的HK-2细胞ERK1/2活化。 结论 Gen可通过阻断MAPK信号通路抑制PTH诱导的HK-2细胞CTGF表达。     

巨噬细胞对内皮细胞系同源盒B2基因和血管内皮生长因子受体mRNA及整合素ανβ3表达的影响

目的　体外观察巨噬细胞(M)对血管内皮细胞同源盒(HOX)B2基因mRNA和血管内皮生长因子(VEGF)受体KDRmRNA及整合素ανβ3表达的影响。　方法　体外培养人脐静脉血管内皮细胞系ECV304,分为(1)ECV304组; (2)ECV304 伴刀豆球蛋白A(conA,终浓度25mg/L)组; (3)ECV304 人M系U937组:ECV304细胞中加入1×105 /mlU937细胞; (4)ECV304 U937 conA组:ECV304中加入1×105 /mlU937细胞及终浓度25mg/L的conA.反应48h后,用免疫荧光技术检测各组ECV304细胞整合素ανβ3的表达情况,并用逆转录聚合酶链反应(RT PCR)技术检测细胞KDRmRNA和HOXB2基因mRNA的表达水平。　结果　ECV304组细胞的整合素ανβ3、KDRmRNA及HOXB2基因mRNA的表达水平分别为6. 7±1. 5、0. 633±0. 012、0. 674±0. 004。ECV304 U937 conA组细胞上述指标较ECV304组均明显上调(P<0. 01 ),分别为10. 2±1. 7、0. 879±0 003、0. 947±0 003。其余两组细胞上述指标与ECV304组比较,差异均无统计学意义(P>0. 05).结论　被conA活化的M通过影响内皮细胞的KDRmRNA、HOXB2mRNA基因及整合素ανβ3的表达,来促进内皮细胞增殖、迁移及与基质黏附,从而调节血管生成。     

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.