丝裂原活化蛋白激酶类和蛋白激酶C在转化生长因子β1诱导肾小管细胞结缔组织生长因子表达中的作用

目的了解转化生长因子β1（TGF-β1）诱导肾小管细胞结缔组织生长因子（CTGF）表达的机制，特别是蛋白激酶C（PKC）和丝裂原活化蛋白激酶（MAPK）在CTGF基因表达中的作用及其对Smad磷酸化的影响。方法分别应用PKC抑制剂G06850以及MAPK的3个组成成分ERK、JNK和p38MAPK的抑制剂PD98059、U0126、SP600125和SB203580阻断相应通路，观察其对TGF．131诱导的CTGF表达以及Smad2／Smad3磷酸化的影响。结果TGF-β1（5μg／L）以时间依赖方式诱导HK-2细胞中Smad2／Smad3的磷酸化，从基础值0．87±0．09上升至2h时高峰2．350±0.11。PKC抑制剂G06850（5μmol／L）和ERK抑制剂PD98059（10μmol／L）、U0126（10μmol／L）可部分抑制TGF-β1诱导的CTGF表达，而p38MAPK抑制剂SB203580（20μmol／L）和JNK抑制剂SP600125（10μmol／L）对TGF-β1诱导的CTGF的表达无影响。PKC抑制剂G06850（5μmol／L）可减少TGF-β1诱导的Smad2／Smad3磷酸化，而ERK抑制剂PD98059（10μmol／L）和U0126（10μmol／L）对Smad2／Smad3的磷酸化没有影响。结论在肾小管上皮细胞中，TGF-β1诱导CTGF的表达需要PKC和Ras／MEK／ERK的参与。PKC以Smad依赖的方式参与肾小管上皮细胞中TGF-β1诱导的CTGF的表达，而Ras／MEK／ERK对CTGF表达的调节不依赖于Smads。     

PD98059对酸性成纤维细胞生长因子诱导的EJ细胞增殖的抑制作用

目的观察细胞外调节蛋白激酶(ERK)激酶MEK1抑制剂PD98059对酸性成纤维细胞生长因子(aFGF)诱导的人膀胱癌细胞株EJ细胞增殖的抑制作用;探讨aFGF诱导EJ细胞增殖的细胞内信号传导途径。方法用不同浓度的aFGF刺激EJ细胞并测定ERK活性;对aFGF诱导增殖的EJ细胞施以不同浓度的PD98059,噻唑蓝(MTT)法检测细胞增殖。结果随aFGF浓度增加,EJ细胞内ERK活性升高,当aFGF浓度为0.6 mg/L,ERK活性是对照组的223.62%; PD98059可使aFGF诱导的EJ细胞增殖比下降,当PD98059浓度为0.1μmol/L,增殖比为46.64%。结论ERK通路是aFGF诱导EJ细胞增殖的重要细胞内信号传导通路,PD98059可抑制aFGF诱导的EJ细胞增殖。     

甲状旁腺激素通过丝裂原活化蛋白激酶信号通路诱导人近曲小管上皮细胞结缔组织生长因子表达

目的 观察甲状旁腺激素（PTH）对人肾小管上皮细胞分泌结缔组织生长因子（CTGF）的影响，并探讨丝裂原活化蛋白激酶（MAPK）信号途径在此过程中的作用。 方法 采用实时定量PCR、Western印迹、报告基因等技术，观察PTH诱导人近端肾小管上皮细胞系HK-2细胞CTGF表达的情况。使用信号通路抑制剂PD98059、U0126阻断信号通路以明确PTH发挥作用的信号途径。 结果 正常HK-2细胞有基础水平的CTGF mRNA和蛋白表达，PTH刺激后其表达水平显著增加。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） A，P ＜ 0.01]。正常HK-2细胞有少量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；MAPK通路抑制剂PD98059、U0126作用后，CTGF mRNA、蛋白、基因启动子表达均明显下降。 结论 PTH可诱导HK-2细胞CTGF表达，其作用可能是通过MAPK信号通路来实现的。     

体外刺激对培养成纤维细胞功能与表达c—fos基因的影响

目的 研究采用碱性成纤维细胞生长因子（bFGF)刺激对体外培养成纤维细胞形态、功能以及表达原癌基因c-fos的影响,探讨成纤维细胞生长因子与原癌基因之间在调控创面愈合中可能的网络机制。方法 将处于对数生长期的乳鼠成纤维细胞分成bFGF刺激组织和对照组,在分别采用bFGF和对照物刺激后继续培养,于刺激后1小时和3、5及7天采集细胞用于形态学和细胞活力检测。同时用SP法对原位培养法和甩片法收集的成纤维细胞检测c-fos基因表达。结果 培养的成纤维细胞经bFGF刺激后其形态较对照明显增大,MTT检测活性明显增设,在刺激后表达c-fos基因显著增加,其中以刺激后1小时最为明显。结论 bFGF刺激可以使培养的成纤维细胞形态与功能发生明显改变,使c-fos基因表达显著增加。结合既往研究表明,c-fos不仅可以直接上调bFGF基因表达,同时bFGF本身也可以诱导c-fos基因表达,表明二者之间可能存在相互作用的网络机制。其可能的调控途径涉及ras以及酪氨酸激酶等。     

丝裂原活化蛋白激酶对大鼠成骨细胞TRPV6表达的影响

目的探讨丝裂原活化蛋白激酶对大鼠成骨细胞瞬时性受体电位香草精受体6（transient receptor poten-tial vanilloid receptor 6,TRPV6）表达的影响。方法采用Wistar大鼠乳鼠,连续酶消化法提取成骨细胞并培养。根据组织形态学、改良Kaplow氏成骨细胞碱性磷酸酶染色、矿化结节茜素红染等方法进行鉴定。实验分组：a）正常对照组;b）PD组（PD98059 5μmol/L;PD98059 10μmol/L;PD98059 20μmol/L）;c）SB组（SB203580 5μmol/L;SB20358010μmol/L;SB203580 20μmol/L）;d）PD＋SB组（PD98059 5μmol/L＋SB203580 5μmol/L;PD98059 10μmol/L＋SB203580 10μmol/L;PD98059 20μmol/L＋SB203580 20μmol/L）。细胞计数法、MTT法检测细胞活性,RT-PCR检测成骨细胞TRPV6 mRNA。所得数据用x-±s表示,采用t检验进行统计学分析。结果随着PD98059和/或SB203580浓度的增加,细胞增殖活性有下降的趋势,二者联合作用时细胞活性低于二者单独作用。细胞计数法检测显示,PD98059与SB203580联合作用时,三种组合中细胞数均显著低于空白对照组,P〈0.01;同时也明显低于二者单独作用组细胞数量。碱性磷酸酶染色显示,联合用药组较单独用药细胞数明显减少,细胞体积变小,突起狭长,ALP染色阳性颗粒减少,随药物作用浓度增加上述变化更加显著。茜素红染色显示,钙结节与对照组比较数量少、体积小;10、20μmol/L联合作用组,细胞数减少更加明显,无钙结节形成。SB203580与PD98059二者联合应用显著抑制TR-PV6 mRNA的表达,5 mmol/L联合作用组即可明显抑制,随着作用浓度增加TRPV6 mRNA的表达量逐渐减少。结论 p44/42途径阻断剂PD98059能抑制成骨细胞增殖,明显降低成骨细胞TRPV6 mRNA表达,减少钙结节形成。p38途径阻断剂SB203580能抑制成骨细胞增殖,明显降低成骨细胞TRPV6 mRNA表达,减少钙结节形成。PD98059与SB203580在抑制成骨细胞增殖、降低成骨细胞TRPV6 mRNA表达、减少钙结节形成的作用方面存在协同作用。     

JNK和TGF-β信号途径协同介导CTGF在瘢痕疙瘩成纤维细胞中过度表达

目的:比较结缔组织生长因子(CTGF)在瘢痕疙瘩成纤维细胞(KF)和正常真皮成纤维细胞(NF)中的表达以及对血清刺激的反应;研究介导CTGF在KF中表达的信号途径.方法:在血清刺激前30 min给予小分子人工合成的信号通路抑制剂预处理,分别为:P13K抑制剂wortmannin(100nM);ERK抑制剂PD98059(50mM);p38 MAPK抑制剂SB203580(10mM);JNK抑制剂SP600125(25 mM);以及TGF-β I型受体抑制剂SB431542(0.1μM、0.5 μM、1μM和10 μM),空白对照组仅加入溶剂DMSO预处理.使用定量实时反转录聚合酶链反应比较CTGF在瘢痕疙瘩成纤维细胞(KF)和正常皮肤来源的成纤维细胞(NF)中的表达.结果:KF血清刺激后CTGF的表达迅速升高,而在NF血清刺激后仅少量上升.JNK抑制剂SP600125和TGF-β I型受体抑制剂SB431542对CTGF表达的升高具有显著的抑制作用(P＜0.05).结论:KF中的CTGF血清反应需要JNK和TGF-β信号途径的协同作用.     

三羟基异黄酮对增生性瘢痕成纤维细胞受体型酪氨酸蛋白激酶-丝裂原活化蛋白激酶信号通路的影响

目的 了解5,7,4'-三羟基异黄酮(genistein)对增生性瘢痕成纤维细胞(HSFb)内受体型酪氨酸蛋白激酶-丝裂原活化蛋白激酶(TPK-MAPK)信号转导通路的影响,探讨genistein抑制瘢痕增生的分子机制. 方法体外分离培养HSFb,以不同浓度genistein(25、50、100μmol/L)处理细胞,再加入10 μg/L碱性成纤维细胞生长因子(bFGF)刺激,用[γ-32P]腺苷三磷酸底物掺入法检测细胞TPK活性;用蛋白质印迹法检测TPK-MAPK通路中主要信号蛋白分子c-Raf、丝裂原激活蛋白激酶激酶(MEK)、细胞外信号调节激酶(ERK)、p38 MAPK、c-Jun氨基末端激酶(JNK)磷酸化蛋白的表达变化.以二甲亚砜溶剂处理的HSFb为对照组. 结果 25、50、100μmol/L genistein作用后,HSFb内TPK活性分别为(7.15±0.35)、(5.62±0.88)、(3.17±0.94)×105 pmol·min-1·mg-1,与对照组(8.92±0.28)×105 pmol·min-1·mg-1比较,差异有统计学意义(P<0.05或P<0.01);细胞内磷酸化c-Raf、MEK1/2、ERK1/2、p38蛋白的含量均有不同程度降低,与对照组比较,差异有统计学意义(P<0.05或P<0.01).genistein各剂量组磷酸化JNK蛋白含量与对照组近似.在genistein预处理前提下,加入bFGF刺激的细胞内TPK活性及各信号蛋白的表达亦呈下降趋势. 结论 genistein可通过抑制细胞受体TPK信号转导途径影响HSFb的增殖与活化,主要信号通路可能为TPK→Raf→MEK→ERK/p38途径.     

丝裂酶原活化蛋白激酶激酶1/2抑制对家兔关节软骨保护作用的研究

目的评价丝裂酶原活化蛋白激酶（mitogen—activated protein kinase，MAPK）信号转导通路中MAPK激酶1／2（MEKI／2）在骨关节炎发病过程中的作用。方法新西兰家兔30只，制作OA模型，随机分成3组，每组10只。从造模术后第4天开始，第1组和第2组分别注射100μmol／L和40μmol／L的PD98059，第3组注射PBS液体作为安慰剂对照组，每周2次。另取10只家兔，正常关节内注射PBS液体作为正常对照组。8周后处死动物，进行股骨髁关节软骨退变的大体评分。用Western Blot印记杂交法测定软骨组织中ERK1／2以及磷酸化ERK1／2的表达。用实时定量PCR方法测定基质金属蛋白酶-1／13（MMp-1／13）的mRNA表达水平。结果与使用PBS的安慰剂对照组相比，使用PD98059的关节软骨破坏明显减轻。磷酸化的ERK1／2在100μmol／LPD98059干预组明显低于40μmol／L干预组和安慰剂对照组。而MMP-1／13的mRNA表达在不同浓度的干预组均低于安慰剂对照组。结论MAPK信号转导通路参与了骨关节炎关节软骨破坏的病理过程。MEK1／2选择性阻滞剂PD98059可以在关节炎动物活体内有效抑制关节炎软骨破坏的程度，该作用可能与其有效抑制ERK1／2的磷酸化激活有关。     

IGF-1介导MAPKs通路在C3H10T1/2细胞成骨分化中的作用

目的 探究胰岛素样生长因子1(IGF-1)介导丝裂原活化蛋白激酶(MAPKs)信号通路在C3H10T1/2细胞成骨分化中的调控作用及机制。方法 不同浓度IGF-1(0、5、10、20 ng/mL)培养C3H10T1/2细胞,碱性磷酸酶(ALP)与茜素红(ARS)染色检测ALP活性、钙盐沉积情况,qRT-PCR法检测成骨特性因子核心结合因子α-1(RUNX2)、成骨分化特异性因子骨桥蛋白(OPN)、骨钙蛋白(OCN)mRNA表达水平,Western Blot法检测MAPK通路蛋白磷酸化表达水平。对数期细胞分为空白组、IGF-1组、ERK通路抑制剂(PD98059)组、PD+IGF-1组、p38通路抑制剂(SB202192)组、SB+IGF-1组,qRT-PCR法检测成骨特性因子RUNX2、成骨分化特异性因子骨桥蛋白(OPN)、骨钙蛋白(OCN)mRNA表达水平。结果 不同浓度IGF-1组ALP显色加深,ALP活性升高,钙盐结节形成增多,RUNX2、OPN、OCN mRNA表达水平升高,磷酸化ERK、p38、JNK蛋白表达增加,具有剂量效应(P<0.05)。与空白组比较,PD组、SB...     

ERK1/2-核因子-кB通路介导乙型肝炎病毒x蛋白抑制过氧化物酶体增殖物激活受体-α表达

目的研究乙型肝炎病毒X蛋白(HBx)对过氧化物酶体增殖物激活受体(PPAR)-α的抑制作用,并探讨其中的内在机制。方法培养人肝癌细胞系HepG2,转染HBx表达质粒,Western blot方法检测PPAR-α、丝裂原活化蛋白激酶(MAPK,ERK1／2)和IкB蛋白的变化,凝胶迁移率实验检测核转录因子(NF)-кB蛋白的活性改变,分别加入MAPK和NF-кB特异性的抑制剂PD98059与吡咯烷二硫代氨基甲酸盐(PDTC),观察PPAR-α蛋白的变化。结果(1)HBx质粒转染HepG2后,与对照组相比,ERK2表达增加,NF-кB被激活,PPAR-α的表达下调；(2)阻断NF-кB后,NF-кB的活性下降,PPAR-α的表达增加；(3)阻断MAPK后,转染HBx表达质粒,NF-кB的活性下降,PPAR-α的表达增加。结论HBx抑制细胞核转录因子PPAR-α的表达,可能与ERK1／2-NF-кB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.     

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.     

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.     

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.