表皮生长因子信号通路对前列腺癌细胞DU145表面整合素α5、β1的调控

目的 探讨表皮生长因子（EGF）信号通路对雄激素非依赖型前列腺癌细胞系DU145表面整合素α5、β1的调控.方法 应用流式细胞术、逆转录聚合酶链反应（RT-PCR）和Western蛋白印迹（Western blot）法测定EGF、丝裂原活化蛋白激酶（MAPK）信号通路抑制剂PD98059对DU145细胞整合素α5和β1表达的影响;采用细胞粘附能力测定和Transwell小室法检测EGF及PD98059对DU145细胞粘附能力和迁移能力的影响.结果 EGF上调DU145细胞表面整合素β1亚基的蛋白和mRNA的表达,分别为对照组的231%和248%（方差值为9.0和24.6,P均＜0.01）,并可促进DU145细胞对纤维连接蛋白（Fn）的粘附和迁移能力.而PD98059则具有相反的作用,下调DU145细胞表面整合素β1亚基的蛋白和mRNA的表达,分别为对照组的60%和63%（方差值为6.3和15.3,P均＜0.01）,并可抑制DU145细胞对Fn的粘附和迁移能力.EGF和PD98059对整合素α1的表达无明显影响.结论 EGF可能通过MAPK信号通路上调前列腺癌DU145细胞表面整合素β1亚基的表达,从而促进DU145细胞对Fn的粘附能力和迁移能力;此调节作用主要发生在mRNA转录水平.     

有丝分裂激活蛋白激酶在人前列腺癌细胞中的激活

目的 探讨前列腺癌（PCa)细胞中有丝分裂激活蛋白激酶（MAPK）的激活。方法 采用免疫沉淀和Western blot方法,检测人PCa细胞株LNCaP及DU－145中磷酸化MAPK的表达及雄激素或表皮生长因子（EGF）对其表达的影响。结果 在DU－145中,磷酸化MAPK表达本底水平比LNCaP高10倍。雄激素和EGF处理后8hLNCaP中MAPK激活水平升高,24h达最高,分别比本底高约10倍和5倍,在DU－145中仅EGF可促使MAPK激活水平升高,8h开始升高,24h达最高,比本底高约10倍。结论 在雄激素非依赖性人PCa细胞增生中,MAPK激活比在雄激素依赖性人PCa细胞中作用大,MAPK激活也参与了雄激素和EGF的增生刺激作用。     

表皮生长因子对人小细胞肺癌细胞Survivin表达的影响及其机制

目的 探讨表皮生长因子(EGF)对人小细胞肺癌NIC-H446细胞中凋亡抑制因子Survivin表达的影响及其调控Survivin的机制.方法 噻唑蓝(MTT)法测定EGF对细胞增殖率的作用.逆转录-聚合酶链反应(RT-PCR)和免疫印迹(Western blot)方法测定EGF对NIC -H446细胞Survivin表达的影响.Western blot方法测定EGF对NIC-H446细胞p38丝裂原活化激酶(p38MAPK)、磷酸化p38MAPK(p-p38MAPK)、c-Jun氨基端激酶(JNK)、磷酸化JNK (p-JNK)、细胞外信号调节蛋白激酶(ERK)、磷酸化ERK(p-ERK)信号通路蛋白的表达影响.结果 EGF可促进NIC-H446细胞增殖,具有浓度-时间依赖性.与对照组(0.36±0.06、0.57 ±0.15)比较,EGF组Survivin mRNA(0.69±0.12)和蛋白(0.89±0.19)表达明显升高(P＜0.01).与对照组(0.29±0.08)比较,EGF组p-p38MAPK蛋白表达水平(0.68±0.27)明显上升(P＜0.01),其他蛋白表达均无明显变化.EGF+ SB203580组Survivin蛋白表达(0.56±0.17)、p-p38MAPK蛋白表达(0.41±0.11)显著低于EGF组(0.92 ±0.21、0.72 ±0.19,P＜0.01),与对照组比较差异无统计学意义.结论 EGF通过活化p38MAPK信号通路上调小细胞肺癌细胞中Survivin的表达,促进细胞增殖,这可能是小细胞肺癌发展的重要机制.     

表皮生长因子受体阻断对前列腺癌细胞增殖的影响

目的：探讨阻断表皮生长因子受体（EGFR）对前列腺癌（PCa）细胞增殖的影响。方法：人PCa细胞株DU－145，分别加或不加抗EGFR单抗C225（20nmol/L)阻断EGFR体外细胞培养7d，收集细胞、计数以观察对PCa雄激素非依赖增殖的影响，并采用免疫沉淀和Western blot方法，探讨阻断EGFR后不同时相点磷酸化有丝分裂原激活下蛋白激酶MAPK，及p27^kipl的表达变化。结果：阻断EGFR与对照相比较可使DU－145细胞增殖被抑制达35％，8h后磷酸化MAPK的表达水平开始降低，p27^kip1表达开始升高，至24h最明显。结论：阻断EGFR可抑制PCa细胞增殖，可能的机制是MAPK的活性降低，使p27^kip1的表达升高而细胞周期被阻。     

ASF1B通过调控P53相关信号通路促进前列腺癌迁移和增殖的研究

目的研究组蛋白伴侣抗沉默功能1B（ASF1B）对前列腺癌（PCa）迁移和增殖能力的影响,探索ASF1B调控P53相关信号通路的具体分子机制。 方法根据TCGA数据库中的数据分析ASF1B在前列腺癌患者中的生存预后情况,使用细胞小干扰RNA（SiRNA）敲低ASF1B表达后,通过Transwell细胞迁移实验比较细胞的运动能力,通过CCK8实验和平板克隆实验比较细胞的增殖能力,使用细胞凋亡实验比较细胞的凋亡率,通过转录组二代测序比较敲低ASF1B后各个信号通路的改变情况,通过Western-Blot实验及Q-PCR实验比较P53相关信号通路分子的蛋白质和mRNA水平变化,以阐明ASF1B对前列腺癌细胞的迁移及增殖能力的影响。 结果SiRNA敲低ASF1B表达后,DU145和PC3细胞的运动能力降低,相同时间内穿过小室的细胞数减少。敲低ASF1B表达后,DU145和PC3细胞的细胞活力和集落形成个数及大小降低,细胞增殖能力下降。敲低ASF1B表达后,DU145和PC3细胞的凋亡率增加。敲低ASF1B表达后,PC3细胞的转录组二代测序结果提示P53信号通路受到调控（P<0.01）。敲低ASF1B表达后,PC3细胞内P53相关通路的P21、IGFBP3、BBC3表达量上升,Cyclin D、Snail、Slug表达量下降。 结论ASF1B以非P53依赖的形式通过P53相关信号通路调控前列腺癌细胞的迁移及增殖,ASF1B有望成为前列腺癌的诊断及治疗的新型靶点。     

EGF信号通路对雄激素非依赖性前列腺癌细胞株DU145细胞周期的影响

目的探讨EGF信号通路影响雄激素非依赖型前列腺癌细胞系DU145细胞周期分子学机理.方法MTT法检测EGF对DU145细胞增殖能力的影响,流式细胞仪检测细胞周期,Western印迹检测细胞周期调控因子的表达情况.结果EGF组细胞增殖能力显著升高,EGF组细胞在S期细胞比例为65.36%,明显高于对照组的44.32%,两者比较差异有统计学意义(P＜0.01);在蛋白质水平,EGF降低了p27表达,而CDK2、磷酸化Rb的表达不同程度增高,p16、p21表达无明显差异.结论EGF刺激导致其下游的信号通路活化,降低p27表达,并导致下游CDK2、Rb及Rb磷酸化水平的变化,最终促进了DU145细胞的增殖能力.     

Gefitinib对前列腺癌DU145细胞EGFR、MAPK、AKt及PKC蛋白表达的影响

目的探讨在Gefitinib 作用下前列腺癌DU145细胞表皮生长因子受体(EGFR)、促分裂原活化蛋白激酶(MAPK)、丝氨酸蛋白激酶(AKt)及蛋白激酶C(PKC)蛋白表达水平的变化.方法使用终浓度为10μmol/L Gefitinib体外作用于DU145细胞,Western blot检测DU145细胞EGFR、MAPK、AKt、PKC蛋白表达水平.结果 经Gefitinib作用后DU145细胞EGFR、Akt蛋白水平分别降低了69.57%和58.31%,而MAPK及PKC 蛋白分别仅降低35.93%和32.7%.结论 Gefitinib作用后DU145细胞发生生长抑制可能和EGFR、Akt蛋白表达抑制有关,而和MAPK及PKC蛋白抑制无关.     

表皮生长因子促进胰腺癌细胞侵袭和转移的实验研究

目的 探讨表皮生长因子（epidermal growthfactor，EGF）促进胰腺癌细胞侵袭和转移的分子机理。方法 EGF对胰腺癌细胞系NOR—P1的增殖、黏附及侵袭能力的影响分别用WST-1细胞增殖实验、细胞黏附实验和Transwell体外侵袭实验检测；MMP-9和MMP-2的活性及表达分别用明胶酶谱分析和Western印迹、RT—PCR检测；NF-κB活性用凝胶电泳迁移实验检测。结果 EGF能够明显促进胰腺癌细胞的侵袭能力，但对胰腺癌细胞的黏附力及增殖并无明显影响；EGF明显上调胰腺癌细胞的NF-κB和MMP-9的活性及表达，但对MMP-2活性及表达无影响；NF-κB抑制物四氢化吡咯二硫代氨基甲酸盐（PDTC）能够明显抑制EGF所诱导的NF-κB活性，同时也抑制EGF所诱导的MMP-9表达及胰腺癌细胞的侵袭力。结论 EGF通过活化NF-κB促进胰腺癌细胞的MMP-9的表达和侵袭力，采用NF-κB抑制剂PDTC阻断NF-κB通路能够降低胰腺癌细胞的侵袭力。     

罗格列酮对多囊肾囊肿衬里上皮细胞p38促分裂原活化蛋白激酶信号通路的影响

目的 探讨罗格列酮对多囊肾囊肿衬里上皮细胞p38促分裂原活化蛋白激酶（MAPK）信号通路的作用。 方法 分别用罗格列酮（RGZ,10 μmol/L）、过氧化物酶体增殖物活化受体γ（PPARγ）抑制剂GW9662（10 μmol/L）、RGZ（10 μmol/L）+GW9662（10 μmol/L）、p38MAPK特异性抑制剂SB203580（10 μmol/L）、SB203580（10 μmol/L）+RGZ（10 μmol/L）处理体外培养的多囊肾囊肿衬里上皮细胞（PKD细胞）2 h后,再用表皮生长因子（EGF）刺激不同时间,另设置空白对照组和单独EGF刺激组。采用Western印迹方法检测p38MAPK、磷酸化p38MAPK（p-p38）、增殖细胞核抗原（PCNA）表达;RT-PCR检测p38 mRNA表达;免疫细胞化学检测c-fos和c-jun的表达。 结果 (1) 与空白对照组相比,EGF显著上调p-p38、PCNA、 c-fos和c-jun的表达（P ＜ 0.01）。(2) 与EGF单独刺激相比,RGZ显著降低p38活化和基因表达（均P ＜ 0.01）。RGZ组、SB203580+RGZ组p-p38、PCNA、c-fos、c-jun表达明显下调（P ＜ 0.01）,两组间差异无统计学意义。(3) 与RGZ组相比,RGZ+GW9662组部分阻断RGZ的下调作用（P ＜ 0.05）。 结论 罗格列酮抑制多囊肾囊肿衬里上皮细胞增殖的作用机制可能与其降低p38MAPK活性,继而抑制PCNA、c-fos及c-jun表达有关。这种抑制作用是部分非PPARγ依赖的。     

PI-3K和p38MAPK通路在EGF诱导PC-3细胞环氧化酶-2表达上调中的作用

目的:研究p38丝裂原激活蛋白激酶(p38MAPK)和磷脂酰肌醇-3激酶(PI/3K)通路在表皮生长因子(EGF)诱导的激素非依赖性前列腺癌(hormone-refractory prostate cancer,HRPC)PC-3细胞环氧化酶2(cyclooxygen-ase-2,COX-2)表达上调中的作用。方法:MTT法检测EGF(0μg/L)、EGF(10μg/L)、EGF(10μg/L)+PI-3K阻断剂(LY294002,20μmol/L)、EGF(10μg/L)+p38MAPK阻断剂(SC203580,20μmol/L)处理后的细胞增殖情况。RT-PCR和Western印迹测定上述处理24h后PC-3细胞COX-2的表达变化,ELISA测定细胞培养液中前列腺素E2(PGE2)的变化。结果:LY294002和SC203580明显抑制EGF刺激后的PC-3细胞增殖(P<0.05)及EGF诱导的COX-2上调和PGE2生成(P<0.05)。结论:PI-3K通路和p38MAPK通路可能参与了EGF诱导的PC-3细胞COX-2的表达上调。     

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.