周期性流体应力刺激对组织工程软骨分化影响的实验研究

目的 研究周期性流体应力刺激对组织工程软骨体外分化的影响,确立良好的动态培养方案。方法 穿刺吸取成年兔骨髓,密度梯度离心法分离扩增骨髓间充质干细胞(Bone marrow derived mesenchymal stem cell,MSC)。以2.0×10~7/ml密度复合于纤维蛋白胶,制成圆柱形人工组织。实验组材料经受周期为0.2Hz流体应力刺激,于转壁生物反应器中培养2周,对照组静止培养,两组均于条件培养基内诱导软骨组织形成。2周后观察大体形态、和组织学形态、Ⅰ型和Ⅱ型胶原免疫组织化学表达,测量细胞活力和胶原、蛋白多糖含量等生化指标。结果 应力刺激组材料的大体形态完整,而对照组材料破碎回缩。实验和对照组均可以诱发材料中MSC分化成为软骨细胞,但流体刺激组表达更高水平的Ⅱ型胶原和蛋白多糖,细胞活力明显高于对照静止培养组(P<0.01)。结论 周期性流体应力刺激明显促进MSC体外软骨分化,转壁生物反应器培养优于单纯静止培养。     

三维动态诱导对自体组织工程软骨远期退变抑制效应的实验研究

目的体外诱导自体骨髓间充质干细胞（aMSC）向软骨细胞分化,验证三维动态诱导培养的软骨分化效率和远期修复效应。方法分离培养多样本aMSC,分别行转壁生物反应器内三维动态诱导（三维动态诱导组）培养和常规二维平面诱导（二维平面诱导组）培养,比较各自的软骨分化效率;收获细胞与注射型蛋白胶混合,修复动物关节软骨缺损。8、12、24、48周后分别取材,观察大体形态和组织学形态,进行组织学评分,比较长期修复效果。结果二维平面诱导时仅出现局部蛋白多糖沉积,只少数细胞表达Ⅱ型胶原;三维动态诱导培养时蛋白多糖沉积明显并广泛表达Ⅱ型胶原,其胶原产量和蛋白多糖含量明显高于二维平面诱导组。在体内实验中,三维动态诱导组：8、12周后缺损完全修复,表面光滑,质地坚硬,与周围软骨紧密结合,组织学表现为类透明软骨结构,24、48周后修复组织与周围界限消失,仍保持类透明软骨的结构。二维平面诱导组：8周后软骨缺损即可被类透明软骨修复,但12周后即开始出现退变,24周后退化明显,软骨组织骨化变薄,48周后则大部分骨性退化,表层残留菲薄纤维组织。结论三维动态诱导培养可提高aMSC的软骨分化效率和远期修复效果,可为深化自体软骨组织工程研究提出新思路。     

人骨髓间充质干细胞向软骨细胞诱导分化的实验研究

目的 研究人骨髓间充质干细胞(human marrow mesenchymal stem cells，hMSCs)在体外单层培养条件下诱导分化为软骨细胞的可行性。方法 取志愿者骨髓9例，密度梯度离心获得hMSCs，进行诱导培养。光镜下观察诱导细胞形态学的改变，免疫组化、原位杂交、RT—PCR等方法检测胶原和糖蛋白的体外表达情况。结果 经诱导后hMSCs形态由长梭形逐渐向多角形转变，原位杂交、免疫组化等检测到Ⅰ、Ⅱ、Ⅲ型胶原表达，RT—PCR检测到Ⅰ、Ⅱ、Ⅲ、X、Ⅺ型胶原、aggrecan等mRNA表达。结论 hMSCs单层诱导培养条件下，能分泌软骨细胞特征性细胞外基质如Ⅱ型胶原、aggrecan等，具有作为软骨组织工程种子细胞来源的可能。     

骨髓基质细胞体外增殖后移植修复关节软骨缺损的实验研究

目的 :用组织工程的方法将骨髓基质细胞体外培养增殖后植入软骨缺损 ,观察关节软骨缺损的修复效果。方法 :抽取兔骨髓基质细胞体外培养增殖后 ,将其与Ⅱ型胶原凝胶相结合 ,植入到兔膝关节实验性关节软骨缺损中 ,对照组的缺损分别置入与髓腔血混合的Ⅱ型胶原凝胶、单纯Ⅱ型胶原凝胶或不作任何处理 ,术后 4、8、12周取材观察及组织学检查。结果 :术后 4周 ,实验组的缺损由透明样软骨样组织充填 ,术后 12周 ,软骨及软骨下骨组织基本修复 ;在对照组缺损 ,软骨下骨在术后 12周亦基本修复 ,但表层软骨主要由纤维组织修复。结论 :骨髓基质细胞来源丰富 ,采集方便 ,经体外培养增殖后 ,足量的未分化细胞与Ⅱ型胶原凝胶载体相结合 ,修复关节软骨缺损的效果较好。     

自组装培养形成软骨组织的研究

目的 探讨通过"自组装"(Self-Assembly)培养技术,以生长分化因子-5(GDF-5)诱导人骨髓间充质干细胞(hMSCs),分化形成软骨组织的可能性及效果.方法 将第3代hMSCs用含GDF-5的软骨诱导液定向诱导培养.3周后重悬细胞,自组装培养.对自组装组织团块经行大体观察、逆转录-聚合酶链反应(RT-PCR)、免疫组织化学、软骨相关染色检测.结果 自组装组织团块有类似于软骨的外观,Ⅱ型胶原mRNA表达明显,组织学显示Ⅱ型胶原和蛋白多糖表达阳性.GDF-5诱导组Ⅱ型胶原免疫组织化学平均吸光度为(0.1678±0.0222),对照组平均吸光度为(0.0908±0.0145),差异有统计学意义(P＜0.05).结论 自组装法培养hMSCs能形成具有软骨分子生物学、组织学和生物力学特性的组织团块,而GDF-5能够增强此过程中细胞的软骨表达.     

转化生长因子-β1基因修饰对骨髓间充质干细胞向软骨细胞分化的影响

目的观察骨髓间充质干细胞经转化生长因子-β1(transforminggrowthfactor,TGF-β1)基因修饰后增殖能力和向软骨细胞分化能力的变化。方法利用脂质体将pcDNA3-TGF-β1基因导入骨髓间充质干细胞,通过大体形态观察、CCK-8测定转染前后骨髓间充质干细胞的增殖代谢能力,同时RT-PCR和Westernblot法检测软骨特异性细胞外基质蛋白Ⅱ型胶原的表达。结果基因修饰后骨髓间充质干细胞倍增能力明显增强,并且Ⅱ型胶原蛋白表达增加。结论经TGF-β1基因修饰的MSCs向软骨细胞分化能力增强,是优秀的软骨组织工程种子细胞。     

羊软骨细胞在生物反应器中的培养和扩增

[目的]探索在旋转生物反应器内，应用微载体技术快速扩增分化良好的羊软骨细胞的方法。[方法]将培养的羊软骨细胞应用Cytodex-3微载体在旋转生物反应器（RCSS）内，进行动态培养，应用倒置显微镜对微载体表面的软骨细胞进行动态观察，并对收获的软骨细胞进行Ⅰ、Ⅱ型胶原的细胞免疫化学染色分析。[结果]关节软骨细胞于1d内贴附于Cytodex-3微载体表面，细胞初期为圆球形、半球形凸起，逐渐向周围伸展，随时间的延长，贴附于微载体的细胞逐渐增多，到培养后期，细胞密度可达最初接种的15～17倍，在微载体上收获的软骨细胞经Ⅰ型胶原的免疫细胞化学染色呈阴性，Ⅱ型胶原染色则呈强阳性。[结论]利用微载体细胞培养技术可简便快速地在体外扩增羊软骨细胞，可为构建组织工程化人工软骨提供大量活性、分化良好的软骨细胞。     

软骨细胞与骨髓基质细胞共培养裸鼠体内构建软骨组织的实验研究

目的：探讨软骨细胞在裸鼠体内促进骨髓基质细胞（BMSCs）向软骨分化并形成软骨组织的可行性。方法：从SD大鼠中分别分离出BMSC和软骨细胞进行体外培养。收集软骨细胞培养上清液,作为BMSCs诱导液从第2代开始进行诱导分化,7天后取出标本,免疫组织化学检测软骨特异性Ⅱ型胶原表达,RT-PCR检测Ⅱ型胶原和aggrecan的mRNA表达。SD大鼠BMSCs与软骨细胞按一定比例（7：3）混匀,取5.0×107个混合细胞/ml的各组细胞悬液接种至壳聚糖生物材料,体外培养一周后植入裸鼠皮下,相同数量的单纯软骨细胞或BMSCs同样方法植入,分别作为阳性对照及阴性对照,1.5×107个软骨细胞同样植入作为低浓度软骨细胞对照。各组均8周后取材检测。结果：经诱导后的大鼠BMSCs的Ⅱ型胶原免疫组化检测阳性,RT-PCR检测Ⅱ型胶原和aggrecanmRNA呈阳性表达;混合细胞组及阳性对照组均形成了成熟的软骨,组织学可见成熟软骨陷窝、异染基质及Ⅱ型胶原表达;BMSCs组仅形成了纤维性组织;低浓度软骨细胞组在局部形成了少量软骨。结论：软骨细胞能在一定程度上提供软骨形成的微环境,诱导BMSCs在裸鼠体内向软骨组织分化并形成软骨组织。 还原     

人肋软骨细胞体外培养中生长代谢及功能的变化

目的　通过检测体外培养的人肋软骨细胞老化过程中Ⅰ、Ⅱ型胶原和蛋白聚糖(aggrecan)的表达变化 ,为组织工程软骨构建的种子细胞选择适宜的回植时机。方法　取体外培养的P1 ～P5人肋软骨细胞 ,通过观察细胞形态 ,细胞增殖率 ,Alcianblue法定量检测每代Aggrecan中GAG含量 ,免疫组化蛋白水平观察Ⅰ、Ⅱ型胶原表达及RT PCR从mRNA水平分析Ⅰ、Ⅱ型胶原及Aggrecan基因表达量。结果　人肋软骨细胞从第 3代起逐渐向成纤维样细胞形态转换 ;每代软骨细胞Aggrecan中GAG含量随传代次数逐渐降低 ,第 3代后处于较低水平 ;Ⅰ、Ⅱ型胶原的表达在蛋白水平及mRNA水平基本一致 ,第 2代以前Ⅱ型胶原表达较强 ,Ⅰ型胶原表达较弱 ,之后随传代Ⅱ型胶原表达减弱 ,Ⅰ型胶原表达逐渐增强 ;而Aggrecan在第 3代以前表达较高 ,从第 4代后明显下降。结论　人软骨细胞体外培养老化过程中综合细胞扩增及细胞功能因素 ,第 2代的软骨细胞 (体外扩增约 18 32 6倍 )可作为构建人组织工程软骨的种子细胞。     

骨形态发生蛋白2和富血小板血浆凝胶对兔骨髓间充质干细胞体外成软骨分化的影响

目的观察富血小板血浆(PRP)凝胶及腺病毒介导的骨形态发生蛋白2(BMP-2)基因转染对兔骨髓间充质干细胞(BMSCs)体外成软骨分化的影响。方法取新西兰大白兔骨髓培养BMSCs,抽取静脉血制备PRP,以Ad-GFP-hBMP-2(BMP-2-BMSCs组)及Ad-GFP(对照组)转染的BMSCs分别与PRP凝胶复合,继续培养。用扫描电镜、MTT检测PRP凝胶的生物相容性,RT-PCR检测各组的Ⅰ型胶原、Ⅱ型胶原、Ⅹ型胶原、蛋白聚糖、SOX-9表达。结果扫描电镜及MTT检测证实PRP凝胶具有良好的生物相容性。RT-PCR分析表明,单层培养的BMP-2-BMSCs组的Ⅱ型胶原、蛋白聚糖和SOX-9的表达水平均高于对照组(P0.05),但Ⅰ型胶原表达水平较对照组明显下降(P0.05),同时Ⅹ型胶原表达水平与对照组相比差异无统计学意义(P0.05);与PRP复合后,BMP-2-BMSCs组的Ⅱ型胶原、蛋白聚糖和SOX-9表达水平较对照组升高(P0.05),而Ⅰ型胶原和Ⅹ型胶原表达水平与对照组比较差异无统计学意义(P0.05)。结论转染BMP-2的BMSCs在PRP凝胶中生长良好,BMP-2基因转染能促进BMSCs的体外成软骨分化。     

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.