人瘢痕疙瘩成纤维细胞的干细胞特性研究

目的探讨人瘢痕疙瘩成纤维细胞是否具有间充质干细胞的生物学特性,从细胞分子学角度为进一步研究瘢痕疙瘩的发病机制提供基础研究资料。方法以人瘢痕疙瘩标本为研究对象,通过组织块贴壁法获得成纤维细胞,用流式细胞术检测细胞表面标志CD29、CD34、CD44及CD90的表达;采用免疫细胞化学法检测细胞波形蛋白、Oct4的表达;将体外诱导细胞向成骨细胞、成软骨细胞、成脂肪细胞方向分化。结果采用组织块贴壁法,从瘢痕疙瘩标本中获得成纤维细胞;经流式细胞术检测瘢痕疙瘩成纤维细胞呈高表达CD29、CD44、CD90等间充质干细胞表面标志;经免疫细胞化学法检测瘢痕疙瘩成纤维细胞的波形蛋白、Oct4呈阳性表达;体外诱导分化结果:瘢痕疙瘩成纤维细胞可向成骨细胞、成软骨细胞和成脂肪细胞分化,具有多向分化潜能。结论人瘢痕疙瘩成纤维细胞具有间充质干细胞的生物学特性,可能是瘢痕疙瘩发生、发展的重要因素。     

人瘢痕疙瘩间充质样干细胞向成骨细胞分化过程中Notch信号表达的研究

目的研究人瘢痕疙瘩间充质样干细胞向成骨细胞分化过程中,Notch 1~4受体的表达情况,探讨Notch信号通路是否参与调控人瘢痕疙瘩间充质样干细胞的成骨分化。方法经患者知情同意后,分离培养人瘢痕疙瘩间充质样干细胞,采用流式细胞术检测CD29、CD34、CD44、CD45及CD90的表达;免疫细胞化学法检测Oct 4的表达;体外诱导其向成骨细胞分化,诱导3周后行茜素红染色;于诱导前及诱导后2、3周,采用实时定量-多聚酶链反应(RT-PCR)及免疫蛋白印迹法(western blot),分别检测细胞Notch 1~4受体mRNA及蛋白的表达。结果流式细胞术结果表明,分离培养的细胞高表达间充质干细胞表型CD29(98.76%)、cD44(98.11%)、CD90(97.86%),不表达造血干细胞表型CD34(0.05%)、CD45(0.03%);免疫细胞化学法检测多能干细胞标志物Oct4呈阳性表达;向成骨细胞体外诱导3周后,茜素红染色可见明显的钙盐结节。RT-PCR和western blot结果显示,随着诱导时间的延长,Notch 1~4受体mRNA和蛋白的相对表达量逐渐减少,差异有统计学意义(P0.05)。结论在人瘢痕疙瘩间充质样干细胞向成骨细胞诱导分化过程中,Notch受体信号的表达逐渐减弱,低水平的Notch信号激活可能有利于瘢痕疙瘩间充质样干细胞的成骨分化。     

婴幼儿血管瘤来源的间充质干细胞的体外多向分化实验

目的 观察婴幼儿血管瘤来源的间充质干细胞是否具有多向分化潜能.方法 应用贴壁筛选法从增生期血管瘤中分离间充质干细胞.将人骨髓中分离的间充质干细胞与切除的儿童包皮中分离的成纤维细胞作为对照.采用特异的诱导培养基,在体外诱导这3种细胞向脂肪细胞、骨细胞和软骨细胞分化.结果 在合适的诱导条件下,血管瘤来源的间充质干细胞和骨髓来源的间充质干细胞均可发生成脂肪、成骨和成软骨分化,而成纤维细胞没有表现出任何分化现象.结论 应用贴壁筛选法从血管瘤分离的间充质干细胞具有多向分化潜能.     

诱导人孤雌胚胎干细胞向类间充质干细胞分化的实验研究

目的探索人孤雌胚胎干细胞在体外向类间充质干细胞诱导分化的方法 ,并鉴定所得细胞的生物学特性。方法人孤雌胚胎干细胞在无血清条件下悬浮培养,形成拟胚体,10d后在含血清条件下使拟胚体贴壁生长,7d后胰酶消化,所得细胞在含血清的培养液中传代、扩增。观察传代、扩增后细胞的形态学变化;用免疫荧光染色和流式细胞技术进行细胞表型分析;取第9代细胞进行成脂、成骨和成软骨诱导,9～28d后行特殊染色及RT-PCR分析。结果人孤雌胚胎干细胞在诱导分化后,形态与骨髓间充质干细胞相似,多次扩增传代后仍保持细胞形态和扩增能力。免疫荧光染色发现,细胞表达中胚层标志波形蛋白(Vimentin)。流式细胞分析显示,细胞表达CD29、CD105、CD166、CD44等间充质干细胞表面标志。特殊染色及RT-PCR分析显示:成骨诱导后,细胞碱性磷酸酶和茜素红染色阳性,碱性磷酸酶和Cbfa-1表达增加;成软骨诱导后,细胞Ⅱ型胶原染色阳性,Ⅱ型胶原和软骨寡聚基质蛋白(COMP)表达增强;成脂诱导后,细胞油红染色阴性,脂蛋白酶和Leptin无表达。结论人孤雌胚胎干细胞可以诱导、分化为间充质干细胞,并具有成骨、成软骨分化潜能。     

人骨膜细胞生物学特性的实验研究

目的 探讨人骨膜细胞体外培养的生物学特性. 方法 以胫骨骨膜组织为材料,采用组织块法分离细胞,完全培养基培养,通过倒置显微镜观察细胞形态学,锥虫蓝染色计数法检侧细胞增殖能力;流式细胞学分析细胞表面抗原.随机分为3组,成骨实验组和成软骨实验组分别加入不同的定向培养剂,对照组加入完全培养基,采用碱性磷酸酶染色、Von Kossa染色、甲苯胺蓝染色、Ⅱ型胶原免疫组化染色检测各组细胞的成骨和成软骨分化指标. 结果 骨膜细胞在体外培养条件下呈贴壁生长,细胞生长曲线证实骨膜细胞传至第9代仍保持良好的增殖能力,流式细胞仪检测证实细胞表面抗原CD90及CD105呈阳性;组织化学染色检测证实成骨实验组分化后细胞碱性磷酸酶及钙结节呈阳性,成软骨实验组分化后细胞蛋白聚糖及Ⅱ型胶原呈阳性,对照组各项指标均生阴性.结论 骨膜细胞体外培养细胞增殖能力强,具有间充质干细胞的特性和良好的成骨和成软骨分化潜能,其定向诱导分化的成骨细胞和软骨细胞均具有各自明显的细胞功能表达.     

人牙周膜干细胞的分离培养及生物学特性研究

目的：分离筛选人牙周膜干细胞，研究其生物学特性并进行初步鉴定。方法：采用STR0-1为标记物以免疫磁珠分离筛选人牙周膜干细胞，观察细胞生长及克隆形成情况，流式细胞仪细胞周期、细胞表型分析，免疫细胞化学染色技术检测STR0-1、Vimentin表达，并测定细胞体外多向分化能力。结果：免疫磁珠法可获得人牙周膜干细胞，细胞具有克隆形成能力，增殖速度低。细胞周期分析大多数细胞处于G0／G1期，为慢周期性；细胞表型分析证实CD146、CD44高表达，CD34、CD45低表达。STR0-1及Vimentin均为阳性染色，矿化诱导和成脂诱导证实该细胞具有多向分化能力。结论：免疫磁珠法是有效的分离纯化牙周膜干细胞的方法。所分离细胞具有干细胞的细胞周期、表型特点及多向分化能力。     

婴幼儿血管瘤间充质干细胞的分离鉴定及其在血管瘤组织中的定位观察

目的 探索周细胞是否是血管瘤间充质干细胞的来源,及间充质干细胞与婴幼儿血管瘤消退过程中的脂肪组织增生的关系.方法 采用贴壁筛选法从增生期血管瘤中分离间充质干细胞,应用流式细胞仪和免疫荧光染色检测细胞抗原表型.免疫组化染色观察CD133和PPAR-γ在增生期血管瘤组织中的表达,并以CD31和α-SMA行共染色.结果 血管瘤间充质干细胞为成纤维细胞样,表达CD133、PPAR-γ、CD105、CD90、CD29和Vimentin,不表达CD45、CD34、CD31和flt-1.部分细胞表达α-SMA.大部分细胞表达PDGFR-β.NG2、Desmin和RGS-5无表达.免疫组化染色证实CD133、PPAR-γ和α-SMA共表达于血管瘤组织的微血管周围.结论 细胞形态和抗原表型初步证实,本研究分离的细胞为间充质干细胞,免疫组化染色证实间充质干细胞存在于血管瘤组织的微血管周围.研究结果提示,周细胞是血管瘤间充质干细胞的来源.     

人瘢痕疙瘩来源干细胞的生物学特性鉴定

目的 分析人瘢痕疙瘩来源干细胞的生物学特性,为进一步研究该细胞在瘢痕疙瘩形成中的作用提供参考.方法 以人瘢痕疙瘩为研究对象,采用酶消化法及传代培养法分离筛选瘢痕疙瘩干细胞.选取原代和(或)第3代贴壁细胞进行生物学特性鉴定:加入CD29-藻红蛋白(PE)、CD34-PE、CD44-异硫氰酸荧光素(FITC)、CD90-FITC、CD45-多甲藻黄素叶绿素蛋白抗体,流式细胞仪检测细胞表面分子标记物CD29、CD34、CD44、CD45及CD90的表达及细胞周期;加入小鼠抗人细胞角蛋白19(CK19)即用型单克隆抗体、鼠抗波形蛋白即用型单克隆抗体,免疫细胞化学法检测CK19、波形蛋白的表达;RT-PCR检测细胞Oct4的表达.取第1代细胞,应用成骨细胞、成脂肪细胞、软骨细胞诱导分化培养液进行诱导分化实验,观察细胞的多向分化能力.结果 传代培养后,细胞形态较为均一,以梭形为主,排列不规则.流式细胞仪检测表明,该细胞高表达CD29、CD44、CD90等间充质干细胞表面标记物,低表达CD34、CD45等造血干细胞表面标记物.细胞周期分析显示67.66%的细胞处于G0/G1期,26.24%的细胞处于G2/M期,6.11%的细胞处于S期.免疫细胞化学法检测显示细胞波形蛋白表达呈阳性、CK19表达呈阴性.RT-PCR法检测显示细胞Oct4表达呈阳性.诱导分化实验表明,细胞可向成骨细胞、软骨细胞和成脂肪细胞分化,具有多向分化潜能.结论 人瘢痕疙瘩内存在间充质样干细胞,这种干细胞可能在瘢痕疙瘩形成中发挥重要作用.

Abstract：

Objective To investigate the biological characteristics of human keloid-derived stem cells (KDSC) in order to further research its role in keloid pathogenesis. Methods Human keloid specimens were harvested to isolate and select KDSC by enzyme digestion and subculturing. Primary and (or) the third generation of KDSC were collected for identification of biological characteristics as follows. (1) After addition of mouse anti-human monoclonal fluorescent antibodies (CD29-PE,CD34-PE,CD44-FITC,CD90-FITC,CD45-PerCP),the expression of cell surface antigen phenotype (CD29,CD34,CD44,CD45,CD90) as well as cell cycle was analyzed by flow cytometry. (2) After addition of mouse anti-human cell keratin (CK19) monoclonal antibody and mouse anti-human vimentin monoclonal antibody,the expression level of CK19 and vimentin was respectively determined with immunocytochemical method. RT-PCR was used to detect the expression of Oct4. The multipotent differentiation capacity of the first generation KDSC was observed with osteogenic,chondrogenic and adipogenic nutrient media. Results After being subcultured,the sizes of cells were similar,and the majority of them were spindle-shaped with disorderly arrangement. The cells highly expressed typical surface markers of mesenchymal stem cells (such as CD29,CD44,and CD90,etc.) with low expression of hematopoietic stem cell surface markers (such as CD34,CD45,etc.). 67.66% of cells were in G0/G1 phase,26.24% of cells were in G2/M phase,and 6.11% of cells were in S phase. Vimentin was positively expressed in KDSC while CK19 was negatively expressed. The expression of Oct4 was also positive. After being cultured in inducing differentiation media,the cells could differentiate into osteoblasts,chondrocytes,and adipocytes. Conclusions Stem cells existing in human keloid,which are similar to mesenchymal stem cells,may play an important role in keloid pathogenesis.     

大鼠骨髓间充质干细胞的分离、培养及表型鉴定

目的 建立大鼠骨髓间充质干细胞分离及培养的方法,探讨体外培养骨髓间充质干细胞的生物学特性.方法 采用密度梯度离心法结合贴壁筛选法分离纯化大鼠骨髓间充质干细胞,传代扩增,测定生长曲线,镜下连续观察细胞的形态变化.流式细胞仪鉴定其表面抗原 CD29、CD34、CD44和CD45的表达情况.结果 原代骨髓间充质干细胞呈集落状生长,细胞呈梭形、纺锤形,呈放射状生长,传代后呈均一的成纤维细胞样.骨髓间充质干细胞生长性状相对稳定,1、3、5代细胞生长曲线基本一致.流式细胞仪鉴定表明,骨髓间充质干细胞CD44、CD29表达呈阳性,CD45、CD38表达呈阴性.结论 采用密度梯度离心法结合贴壁培养法能获得纯度较高的骨髓间充质干细胞,并且在体外培养条件下可大量增生,形成形态均一的细胞集落,可以作为组织工程中种子细胞的来源.     

真皮成纤维细胞多向分化潜能的研究进展

真皮成纤维细胞起源于胚胎中胚层间质细胞,是构成体内疏松结缔组织的主要细胞成分.以往认为,真皮成纤维细胞在机体发育过程中是分化完全的终末细胞,不具备多向分化潜能,只能作为真皮组织的种子细胞.近年来研究发现,真皮成纤维细胞能够表达间充质干细胞相关标志物,具有多向分化潜能,在特定条件下能够向骨、脂肪、软骨、肌腱、神经以及胰岛等多胚层组织器官分化,可能成为组织器官构建的种子细胞来源.现将真皮成纤维细胞的多向分化潜能研究现状进行综述.     

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.