人表皮干细胞的体外分离培养和鉴定

目的:探讨人表皮干细胞的体外快速分离培养及鉴定方法。方法:中性蛋白酶和胰蛋白酶两步法从手术切除的人包皮组织中分离表皮层和真皮层,并获得表皮单细胞悬液,采用Ⅳ型胶原铺板选择性粘附、分离和角质形成细胞无血清培养基(K-SFM)培养表皮干细胞。倒置显微镜下观察培养细胞的生长状况,检测细胞克隆形成率,免疫组化染色观察表皮干细胞标志物β1整合素和角蛋白19(K19)的表达;以角质形成细胞作为对照。结果:组织学观察显示,培养24h后细胞呈克隆状生长;所分离、培养细胞的克隆形成率高于对照角质形成细胞组;免疫组化染色显示,培养细胞β1整合素及Kl9均呈阳性表达。结论:运用Ⅳ型胶原粘附结合K-SFM培养可以实现人表皮干细胞的体外快速分离和培养。     

皮肤干细胞在胎皮中分布的免疫组织化学研究

目的 采用免疫组织化学方法研究不同时期胚胎皮肤中的干细胞，分析皮肤干细胞的形态、分布特点及发育过程中在胎儿皮肤中的迁徙、增殖分化特征，探讨皮肤干细胞与皮肤发生发育的关系。方法 不同发育时期胎儿皮肤，取材、固定、制成石蜡切片，SP法检测整合素-β1、角蛋白19（K19）、K14、K10和PCNA的表达。结果 胚胎发育期可见整合素-β1阳性的细胞在基底层散在分布。随胎龄增加，整合素-β1表达减弱，表达范围减小。同时，胚胎发育的不同阶段K19均在表皮基底层强烈表达。表皮分层期后，K14阳性细胞从基底层向上延伸至亚基底层。而K10作为表皮终末分化细胞的标志，主要分布在表皮的中层和外层。此外，在毛囊发育过程中，胎皮表皮嵴的细胞相互聚集成团，形成毛囊初级原基，表达整合素-β1、K19、K14及PCNA为阳性。随着毛囊的形成、成熟，皮肤干细胞主要聚集在与表皮相延续的外根鞘、毛囊隆突部及毛母质，表达整合素-β1、K19、K14和PCNA为阳性。结论 （1）皮肤的发生、发育与角蛋白的程序性改变密切相关；（2）毛囊的发生、发育受到毛乳头的诱导作用。毛囊成熟期后，皮肤干细胞主要迁移至与表皮相延续的外根鞘、毛囊隆突部及毛母质等处。此外，还发现毛乳头及其周围组织内分布着单核样细胞表达整合素-β1、K19和K14为阳性。     

正常皮肤和瘢痕组织表皮干细胞定位与增殖分化特征的比较性研究

目的采用特殊染色法研究少儿与成年人大面积重度烧伤后瘢痕组织表皮干细胞分布与表达β1整合素和角蛋白19、14、10(K19,K14,K10)的特征与规律,在此基础上确定表皮干细胞及短暂扩充细胞分布、数量的差异以及这些改变与瘢痕愈合关系.方法分别取4～12岁少儿及35～53岁成年人2组健康皮肤及大面积深度烧伤后瘢痕组织.采用免疫组织化学SP法检测表皮干细胞、短暂扩充细胞特异表达的β1整合素和K19以及分化表皮细胞表达的K14和K10.结果瘢痕组织表皮基底层表达β1整合素与K19的阳性细胞数较健康皮肤明显减少,阳性强度降低.瘢痕组织表皮中表达K14的阳性细胞仅位于表皮底部2～3层,明显少于健康皮肤,而K10表达阳性细胞则较健康皮肤分布广泛.结论瘢痕组织表皮基底层具有增殖能力的表皮干细胞和短暂扩充细胞明显少于健康皮肤,且瘢痕组织表皮干细胞的分化过程与健康皮肤不同,处于有丝分裂后分化阶段的细胞比例降低,而终末分化细胞的比例明显增高.提示瘢痕组织表皮的增殖能力下降,细胞的分化行为紊乱,这可能是瘢痕组织表皮结构与功能改变、愈合能力下降的原因之一.     

成人正常皮肤和瘢痕组织表皮干细胞定位与表达特征的比较研究

目的采用免疫组织化学染色方法研究成人正常皮肤和瘢痕组织表皮干细胞定位与表达β1整合素和角蛋白19,14,10(K19,K14,K10)的特征与规律,探讨两种组织表皮干细胞表达特征的差异与烧伤后瘢痕愈合的关系.方法分别取成年人健康皮肤6例和大面积深度烧伤后瘢痕组织6例.采用免疫组织化学Elivision两步法检测表皮干细胞、短暂扩充细胞特异表达的β1整合素和K19以及分化表皮细胞表达的K14和K10.结果瘢痕组织表皮基底层表达β1整合素与K19的阳性细胞数较健康皮肤明显减少,阳性强度降低.瘢痕组织表皮中表达K14的阳性细胞仅位于表皮底部2～3层,明显少于健康皮肤,而K10表达阳性细胞则较健康皮肤分布广泛.结论瘢痕组织表皮基底层干细胞和短暂扩充细胞明显少于健康皮肤,且瘢痕组织表皮干细胞的分化过程与健康皮肤不同,处于有丝分裂后分化阶段的细胞比例降低,而终末分化细胞的比例明显增高.提示瘢痕组织表皮的修复能力下降,细胞的分化行为紊乱,这可能是瘢痕组织表皮结构与功能改变、愈合能力下降的原因之一.     

人胎儿表皮干细胞的体外分离培养及基因转染

目的：探讨人胎儿表皮干细胞体外分离培养的方法以及作为体外基因转染靶细胞的可行性。方法：利用Ⅳ型胶原快速贴附法分离人胎儿表皮干细胞，以人胎儿成纤维细胞条件培养液配制表皮干细胞培养基，通过角蛋白19（K19）和整合素β1免疫组化染色、细胞周期分析及克隆形成率测定，对培养细胞进行鉴定。采用脂质体介导法，以含血管内皮细胞生长因子165（VEFG165）基因片段的真核表达载体pcDNA3.1(pcDNA3.1/VEGF165)转染培养细胞；采用病毒载体介导法，以含报告基因绿色荧光蛋白（GFP）的重组腺相关病毒载体（raav/GFP)转染培养细胞。应用免疫组化染色及荧光显微镜观察检测转染效果。结果：人胎儿表皮干细胞呈明显克隆性生长、克隆形成率高，G1期细胞比例明显高于普通基底层角质细胞，K19和整合素β1免疫组化染色呈强阳性。pcDNA3.1/VEGF165转染的表皮干细胞VEGF165免疫组化染色阳性，raav/GFP转染的表皮干细胞呈现强荧光。结论：利用Ⅳ型胶原快速贴附法及人胎儿成纤维细胞条件培养基，可初步实现人胎儿表皮干细胞的分离培养。以质体为介导或以腺相关病毒为载体进行人胎儿表皮干细胞的体外基因转染是可行的。     

不同发育阶段人皮肤表皮干细胞增殖分化特征及其与创面修复结局关系的研究

目的从细胞分化角度研究人胎儿期、少儿期、成年人期皮肤中表皮干细胞增殖分化特征,以及这些特征与创面修复结局的关系.方法分别取因创伤等原因致流产的22～24周龄胎儿和4～12周岁少儿、35～53岁成年人3组全层皮肤.采用免疫组化方法检测表皮干细胞特异表达的β1整合素和细胞角蛋白19(K19).结果胎儿期皮肤表皮基底层细胞β1整合素和K19染色均为强阳性.少儿期表皮基底层细胞中60%～80%的细胞表达β1整合素和K19.成年人表皮基底层中表达β1整合素和K19的细胞较少儿组进一步减少,且染色强度较弱.结论本实验结果提示,胎儿期表皮基底层增殖细胞均为表皮干细胞和短暂扩充细胞,而少儿期表皮基底层中部分细胞为于细胞和短暂扩充细胞,成年人期干细胞与短暂扩充细胞所占的比例则进一步降低.这种干细胞增殖分化的差异可能与三种不同发育阶段皮肤损伤的完全与不完全修复有关.     

快速贴壁法分选表皮干细胞及其评价

目的:认识表皮干细胞对IV型胶原的黏附特性,评价重复利用IV型胶原以快速贴壁法在分选表皮干细胞中的作用。方法:未包被胶原培养瓶的细胞作为对照组I,首次IV型胶原和三次IV型胶原包被的培养瓶分别作为实验组I和实验组II,将包被IV型胶原并曾黏附细胞的培养瓶消化后作为实验组III。人角质形成细胞分别接种其上,15min后对贴壁细胞进行显微摄像并计数,数据用SAS软件分析。对贴壁细胞的生长及增殖活性进行观察,并用β1整合素、K19对贴壁的细胞进行鉴定。结果:与对照组相比,胶原包被组的贴壁细胞数明显增多(P≤0.05),并于5天铺满培养瓶底,而对照组12天后仍未铺满瓶底。各实验组细胞15min贴壁数无明显差异(P>0.05)。贴壁细胞β1整合素和K19表达阳性。结论:表皮干细胞对IV型胶原具有较好的黏附特性,利用快速贴壁法可以得到较高纯度的表皮干细胞,重复利用IV型胶原对表皮干细胞的黏附特性几乎无影响并可节约费用。     

成人正常皮肤和瘢痕组织表皮干细胞定位与表达特征的研究

目的：观察成人正常皮肤和瘢痕组织中表皮干细胞定位与β1整合素和角蛋白19、14、10（K19、K14、K10）的表达，探讨两种组织表皮干细胞表达特征的差异。方法：取6例大面积深度烧伤患伤后1年的增生性瘢痕组织，另取6例健康志愿对应部位的全层皮肤。采用免疫组织化学Eivision两步法，检测表皮干细胞、短暂扩充细胞特异表达的β1整合素和K19以及分化表皮细胞表达的K14和K10。结果：瘢痕组织表皮基底层表达β1整合素与K19的阳性细胞数较正常皮肤明显减少，阳性强度降低，其表皮中表达K14的阳性细胞仅位于表皮底部2－3层，而K10表达阳性细胞则较正常皮肤分布广泛；瘢痕组织皮肤的分化过程亦不相同，处于有丝分裂后分化阶段的细胞比例降低，而终末分化细胞的比例明显增高。结论：瘢痕组织表皮的修复能力下降。细胞的分化行为紊乱，可能是导致瘢痕组织表皮结构与功能改变、愈合能力下降的原因之一。     

去分化表皮干细胞的来源鉴定和分析

目的：利用染色体特异性分析方法鉴定去分化表皮干细胞的来源。方法：包皮皮片去除皮下脂肪后,中性蛋白酶消化过夜,分离表皮和真皮。分离的表皮片用Ⅳ型胶原反复粘贴并冲洗去除表皮干细胞。处理后的表皮片经免疫组化鉴定无表皮干细胞后移植到雌性BALB／c裸鼠背部全层皮肤缺损创面,5d后用免疫组化法检测皮片内角蛋白10（CK10）、CK19和β1整合素的表达,然后用Ⅳ型胶原粘贴法分离皮片内去分化来源的表皮干细胞,并采用PCR的方法检测去分化细胞内的Y染色体。结果：未经处理的表皮片基底部细胞呈CK10染色阴性,CK19和β1整合素染色阳性;Ⅳ型胶原处理后的表皮片内细胞全呈CK10染色阳性。而去基底皮片移植后5d,在皮片的基底侧重新出现CK10染色阴性、CK19和β1整合素染色阳性的细胞。Ⅳ型胶原粘贴分离去分化来源的表皮干细胞,结果表明,移植皮片组在10min内约有4．56％的贴壁细胞出现,而未移植皮片组3h内无贴壁细胞出现。PCR分析结果显示在上述贴壁细胞内能检测到Y染色体的特异序列,而宿主来源的组织检测不到。结论：去分化表皮干细胞来源于移植皮片内成熟表皮细胞的去分化,而非宿主体内的干细胞。     

细胞外基质对表皮干细胞缝隙连接介导的细胞间通讯的影响

目的：探讨细胞外基质对表皮干细胞间通讯的调节机制,为理解皮肤创伤愈合的信号传递提供实验依据。方法：体外分离和培养人表皮干细胞（n=8）,流式细胞仪检测抗原表达。细胞模型是2×10^6表皮干细胞接种在胶原包被的培养皿表面,实验组为表皮干细胞＋Ⅳ型胶原基质组（n=8）,对照组为表皮干细胞＋Ⅰ型胶原／层粘连蛋白基质组（n=8）,和表皮干细胞培养于无胶原包被的60mm平皿组（n=8）。Epilife无血清培养基培养7天后,用激光共聚焦显微镜观察培养表皮干细胞缝隙连接蛋白（connexin）表达、单细胞显微注射荧光示踪剂检测在培养表皮干细胞之间缝隙连接细胞间通讯。结果：培养的人表皮干细胞抗C-Kit、CK14、CK19、β1-整合素、P63染色阳性,流式细胞学检查示C-Kit、CK14、CK19、β1-整合素、P63阳性率分别是（91．50±4．72）％、（88．54±6．28）％、（90．38±7．10％、（89．54±5．61）％和（87．38±4．64）％。培养7天后,在Ⅳ型胶原组,（90±4．11）％的细胞表达表皮干细胞表型;在无胶原基质组,细胞生长数量少,（50±6．20）％的细胞表达表皮干细胞表型;在Ⅰ型胶原／层粘连蛋白基质组,只有少于（10±3．54）％的细胞表达表皮干细胞表型,（90±4．83）％的细胞表达表皮细胞表型;此外,保持特异性标志的表皮干细胞Connexin表达图不同于有表皮细胞特征的细胞。因为皮肤的创伤愈合过程伴随着细胞外基质和生长因子的改变,随之是广泛的表皮干细胞的细胞分裂,分化,和迁移,而相似的改变对于体内皮肤创伤的修复过程极为重要。结论：细胞外基质通过Connexin调节表皮干细胞间通讯,不同Connexin表达模式允许第二信使分子和细胞代谢产物的不同通透性,因此协调细胞和组织功能。     

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.     

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.     

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.