力学刺激促进骨髓基质干细胞体外软骨分化

目的探讨离心力刺激对猪骨髓基质干细胞(BMSCs)体外成软骨分化的作用,以及对三维支架上构建组织工程化软骨的影响,明确力学刺激与细胞分化及组织形成的关系,为体外软骨构建提供适当参数。方法抽取8周龄猪髂嵴骨髓,应用贴壁法分选单个核细胞,体外培养扩增后获得第2代BMSCs,以5.0×107/cm3的细胞密度接种到聚羟基乙酸(PGA)制成的圆柱形三维支架上,7d后分成4组,在不同的力学条件及诱导条件下培养。8周后取材,行相关检测。结果力学诱导组形成的组织呈白色,细腻光泽,形状规则,体积无明显改变,有良好的弹性和硬度,并具有典型的软骨陷窝结构和大量软骨特异性细胞外基质,Ⅱ型胶原及丰富的聚合蛋白多糖(GAG)成分。GAG含量为(6.0±1.2)mg/g,抗压强度为(2.2±0.8)kPa,弹性模量为(7.4±1.6)kPa。各项指标均明显优于其他各组。结论力学刺激有利于促进BMSCs成软骨分化,并在三维支架材料上构建组织工程化软骨。     

力学刺激促进软骨细胞与骨髓基质干细胞共培养体外软骨分化

目的：研究不同的应力刺激对软骨细胞与骨髓基质干细胞（BMSCs）共培养体外构建组织工程化软骨的影响。方法：分离、培养、扩传兔MSCs及软骨细胞,二者按7：3比例混和,以5．0×107／ml的细胞密度接种于聚羟基乙酸（PGA）支架上,一周后根据不同的施加力分为4组：离心组、摇床组、搅拌组,静止培养作为对照组。6周后取材行相关检测。结果：三受力组形成的细胞材料复合物基本保持原来的体积与外形。HE染色结果显示大量成熟软骨陷窝形成,细胞外基质沉积均匀;Safranin-O及甲苯胺兰染色显示有大量的GAG形成,免疫组化检测II型胶原表达强阳性。三受力组标本组织湿重、体积、GAG含量等指标均优于对照组。结论：力学刺激有利于促进少量软骨细胞与BMSCs共培养体外软骨分化;并在三维支架材料上构建组织工程化软骨。     

骨髓基质干细胞复合改性的聚羟基丁酸-羟基异戊酯体外构建组织工程化软骨

目的 探讨应用骨髓基质干细胞(BMSCs)复合光接枝改性的聚羟基丁酸-羟基异戊酯(PHBV)构建组织工程化软骨的可行性. 方法 将3代绵羊骨髓基质细胞接种于光接枝改性的三维PHBV支架材料上,24 h后以成软骨诱导液培养,3周后,复合培养物行扫描电镜观察,组织学观察,测定糖胺聚糖(GAG)含量.并将复合物埋植于绵羊腹部皮下,4周后取出,行大体及组织学观察. 结果 经成软骨诱导后,扫描电镜下,BMSCs的突触逐渐变短,由长梭形向扁平形转变,分泌基质量亦明显增多.组织学观察见细胞支架复合物阿利新蓝、番红O、Ⅱ型胶原免疫组化染色均呈阳性.GAG含量测定示诱导3周后,细胞分泌的GAG量(1306.7±192.3)明显高于未经诱导的BMSCs(205.0±26.2)(P<0.001),但仍低于正常软骨细胞(1969.2±235.3)(P<0.001).复合物埋植于皮下4周后,其内炎症细胞浸润明显,但番红O、Ⅱ型胶原免疫组化染色均呈阳性. 结论 以BMSCs为种子细胞,复合改性的PHBV,可于体外构建出软骨样组织,但该组织的理化特点与正常软骨仍有差距.     

血清浓度影响骨髓基质干细胞体外软骨分化的实验研究

目的 探讨含有不同浓度胎牛血清的成软骨分化诱导液对骨髓基质干细胞(BMSCs)体外分化的影响,明确体外培养用血清在细胞分化中的作用,为软骨的体外组织构建提供技术参数.取第2代猪BMSCs,以5×107个细胞/cm3的密度接种到聚羟基乙酸(PGA)制成的圆盘状支架上(直径5 mm,厚度2 mm),7 d后分别应用含0%、5%、10%血清浓度的诱导液(诱导因子包括TGF-1、IGF-Ⅰ及地塞米松)进行体外持续性诱导培养.8周取材行组织湿重测量、GAG含量定量分析、大体观察、组织学、组织化学及免疫组织化学检测.结果 10%血清组复合物外观瓷白色,坚硬细腻,体积和外形均无明显变化.组织学及免疫组织化学检测结果显示有典型的软骨陷窝,大量的软骨特异性细胞外基质成分,组织湿重和GAG定量亦明显高于其它两组;3%血清组复合物体积缩小,有少量陷窝样结构及软骨特异性胞外基质聚集;而无血清组复合物缩小,松软易碎,未见典型的软骨陷窝和软骨特异性基质成分.结论 体外诱导培养BMSCs构建组织工程软骨过程中,10%浓度的血清成分有利于BMSCs成软骨分化.     

β1转化生长因子浓度对体外诱导骨髓间充质细胞构建软骨的影响

目的 探讨β1转化生长因子（TGF-β1）浓度对体外诱导猪骨髓间充质细胞（BMSCs）构建组织工程化软骨的影响，明确TGF-β1诱导剂量对细胞分化的作用，为体外软骨构建提供适宜的诱导因子应用浓度参数。方法 抽取8周龄猪髂嵴骨髓，应用贴壁法分选单个核细胞，体外培养扩增后获得BMSCs，收集第2代细胞，以5×10^7个／cm。细胞的密度接种到聚羟基乙酸（PGA）制成的圆柱形三维支架材料上（直径5mm，厚度2mm），7d后应用不同浓度TGFβ1（A组：5ng／ml、B组：10ng／ml、C组：20ng／ml、D组：50ng／m1）与IGF-1（50ng／m1）及地塞米松（40ng／m1）组成诱导剂，分别进行体外诱导培养。8周后取材行大体观察，体积、湿重及聚合蛋白多糖（GAG）定量，组织学及Ⅱ型胶原免疫组织化学等检测。结果 B、C、D组形成细胞材料复合物组织学结构较为类似，有明显的软骨陷窝，分布有大量Ⅱ型胶原及GAG；A组软骨陷窝结构较少，胞外基质染色较浅。B、C、D组的组织湿重、体积和GAG含量均明显高于A组。结论 诱导三维支架上的BMSCs体外构建组织工程化软骨过程中，10ng／ml的TGF-β1诱导浓度具有良好的促分化效能，TGF-1的促分化作用并未表现出明显的剂量依赖性。     

胎猪BMSC体外构建软骨的实验研究

目的比较胎猪骨髓间充质干细胞（Bone Marrow Mesenchymal Stem Cells,BMSCs）和成年猪BMSCs构建软骨能力的差异,寻找合适的同种异体组织工程软骨种子细胞来源。方法通过剖腹产手术获得胎龄为70 d的胎猪,胎猪骨髓液贴壁培养获得胎猪BMSCs;抽取成年猪骨髓液,经贴壁培养法获得成年猪BMSCs。两种细胞体外扩增培养后,观察第3代细胞形态,并进行成骨、成脂和成软骨诱导。分别取两种细胞以1×108 cells/mL的细胞终浓度,接种于聚乳酸包埋的聚羟基乙酸支架,体外诱导培养8周后取材。通过大体观察、糖胺聚糖（GAG）含量测定、总胶原含量测定、组织学,以及免疫组化等方法,对两种细胞构建的组织工程软骨的相关生物学特性进行比较。结果胎猪BMSCs比成年猪BMSCs具有更好的增殖和成骨、成脂和成软骨能力。胎猪BMSCs构建的软骨有良好的软骨外观,而且GAG含量和总胶原含量均高于成年猪BMSCs构建的软骨（P<0.01）。组织学和免疫组化显示,胎猪BMSCs构建的软骨组织结构致密,基质及Ⅱ型胶原显色程度均明显强于成年猪BMSCs构建的软骨。结论胎猪BMSCs是组织工程软骨较好的种子细胞来源。     

骨髓间充质干细胞体外构建组织工程化半月板

目的探索以骨髓间充质干细胞（BMSCs）为种子细胞,在体外构建具有完整内侧半月板形态的软骨样组织的方法。方法运用模具制备内侧半月板形的PGA/PLA支架。抽取犬骨髓,分离培养BMSCs,将其接种于支架材料上,5 d后使用软骨诱导液培养。体外培养6周后,行大体观察、组织学检测及生物力学检测。结果细胞材料复合物能够较好地维持半月板三维立体结构,形成了表面光滑、触之有弹性的瓷白色软骨样组织。 HE染色可见典型的软骨陷窝出现,说明成熟软骨组织的形成。Safranine O染色证实有蛋白聚糖基质产生。生物力学检测显示,新生组织弹性模量达正常半月板组织的12.7%。结论 BMSCs通过体外诱导,可在体外分化为较成熟的软骨组织,并构建出组织工程化半月板。     

软骨细胞诱导骨髓基质细胞构建软骨的体内外比较

目的 应用软骨细胞诱导骨髓基质细胞(Bone Marrow Stromal Cells,BMSCs)体外构建软骨,比较其体内植入前后软骨相关生物学特性的差异,探讨共培养构建软骨临床应用的可行性.方法 体外分别培养扩增猪关节软骨细胞和BMSCs,两者按2:8比例混合(软骨细胞:BMSC),以5.0×107/ml的细胞终浓度接种于聚乳酸包埋的聚羟基乙酸支架,体外培养8周后部分标本植入裸鼠皮下,再经体内8周后取材.通过大体观察、糖胺聚糖含量(GAG)测定、生物力学测试、组织学,以及免疫组化等方法对体内植入前后标本的软骨相关生物学特性进行比较.结果 体外培养8周时,所有标本均形成了软骨样组织,但质地较软,组织结构相对较为松散.体内植入8周后,共培养构建软骨能维持良好的软骨外观,而且GAG含量及弹性模量均明显高于体外标本(p＜0.01),组织学及免疫组化显示体内标本的组织结构致密,基质及Ⅱ型胶原显色程度均明显强于体外标本.结论 软骨细胞诱导BMSCs构建的软骨在体内皮下环境中能维持良好的软骨特性,而且植入体内后能继续向成熟软骨发育.     

组织工程骨软骨复合物的构建与形态学观察

目的探讨采用组织工程技术构建骨软骨复合物的可行性。方法将骨髓基质细胞(BMSCs)成诱导软骨后接种于快速成形的三维支架材料聚乳酸／聚羟乙酸共聚物(PLGA)构建组织工程软骨，经成骨诱导的BMSCs接种于聚乳酸／聚羟乙酸共聚物／磷酸三钙(PLGA／TCP)构建组织工程骨，在体外分别培养2周后，将两种工程化组织及两者以无损伤线缝合形成的组织工程骨软复合体分别植入自体股部肌袋，术后8周取材，行组织学观察。结果术后组织学观察表明。组织工程软骨在体内可形成软骨组织组织工程骨在体内可形成骨组织，两者的复合体在体内可形成骨软骨复合物。结论以骨髓基质细胞为种子细胞、以快速成形的生物降解材料为支架体外构建的组织工程骨软骨复合物，可在体内形成骨软骨组织，有望用于骨软骨缺损的修复。     

骨髓诱导分化内皮细胞构建组织工程心脏瓣膜的实验研究

骨髓基质干细胞（BMSCs）在特定培养条件下能够诱导分化为内皮细胞,是构建组织工程心脏瓣膜（TEHV）较有前景的种子细胞来源.我们研究探讨应用BMSCs诱导分化的内皮细胞和猪去细胞瓣膜支架体外构建TEHV的可行性.     

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.