Notch信号通路在小鼠肝癌细胞H22增殖凋亡中的作用及意义

目的 观察Notch信号通路在小鼠肝癌细胞H22增殖和凋亡中的作用,并探讨其可能的机制.方法 培养小鼠肝癌细胞株H22,将细胞随机分为A、B、C组,分别加入Notch信号激活剂rhNF-κB、抑制剂DAPT及PBS共培养48 h.用MTT法检测细胞吸光度值(A值)观察细胞增殖情况,流式细胞术检测细胞凋亡率,应用免疫组化法检测各相关处理过的细胞株,RT-PCR、Western blotting法分别检测H22细胞中的Notch1、Hes1、Bcl-2 mRNA及其蛋白.结果 培养24、48、72、96 h后,A、B组与C组比较,细胞增殖差异明显(P均<0.05).A、B、C组细胞凋亡率分别为25.52％±2.13％、0.91％±0.18％、8.91％±1.50％,A、B组与C组比较差异明显(P均<0.05).与C组比较,A组细胞中Notch1、Hes1、Bcl-2 mRNA及其蛋白表达量均显著增加(P均<0.05),B组细胞中Notch1、Hes1、Bcl-2 mRNA及其蛋白表达量均显著降低(P均<0.05).结论 Notch1信号通路在抑制小鼠肝癌细胞株H22增殖、促进其凋亡中发挥了重要的调控作用,其机制可能与调节靶基因Hesl、Bcl-2表达有关.     

CIK/NK细胞对荷骨肉瘤NOD/SCID小鼠肺转移瘤的杀伤作用

目的制备骨肉瘤U-2OS细胞NOD/SCID小鼠肺转移模型,探讨CIK/NK细胞对肺转移瘤的杀伤作用。方法 60只NOD/SCID小鼠随机分为3组(每组20只),A组:每只鼠经尾静脉接种U-2OS细胞2×106(0.2 ml)后24 h,输注CIK/NK细胞(2×107/0.2 ml);B组:每只鼠经尾静脉接种U-2OS细胞2×106(0.2 ml)后24 h,注射生理盐水0.2 ml;C组:每只鼠经尾静脉注射生理盐水0.2 ml后24 h,注射生理盐水0.2 ml。比较各组小鼠生存时间及肺部肿瘤负荷情况。结果 B组接种U-2OS细胞后29 d内小鼠全部死亡,其中16只肺部出现肉眼可见瘤块;A组接种U-2OS细胞后60 d内小鼠死亡8只,肺部均发现肉眼可见瘤块,余12只肺部均无瘤块。A组平均生存时间显著高于B组,差异有统计学意义(P<0.05),而与C组比较差异无统计学意义(P>0.05)。B组小鼠死亡时体重明显低于A组,而肿瘤细胞比例明显高于A组(P<0.05)。结论 CIK/NK细胞在NOD/SCID小鼠体内有肯定的抗骨肉瘤肺转移瘤效果。     

ECT评价超声微泡治疗小鼠肝癌 腹水转移皮下瘤的实验研究

目的研究67Ga ECT肿瘤显像评价低功率超声辐射微泡治疗小鼠肝癌腹水转移皮下瘤的生物学效应.方法 KM昆明种小鼠6只建立小鼠H22腹水转移皮下瘤模型,随机分为A、B、C三组.A组：单纯低功率超声治疗肿瘤;B组：微泡剂＋低功率超声治疗肿瘤.C组：正常对照组,观察三组动物抗瘤效应、组织学、免疫组化检测PCNA、CD34蛋白表达、67Ga ECT肿瘤显像.结果三组小鼠肿瘤处理前后体积变化及生长率比较,B组肿瘤治疗后体积明显被抑制及生长率下降.A、C二组比较：t=0.91,P＞0.05;B、C二组比较：t=2.95,P＜0.05.形态学改变：B组可见明显的肿瘤血管栓塞及肿瘤坏死.免疫组化检测：PCNA、CD34在C组、A组呈强阳性表达,而B组表达明显下降.A、B、C三组PCNA阳性指数（PI）分别为89.9%、37.4%、91.7%;CD34 MVD计数分别为78.4%、31.2%、77.1%.67Ga ECT肿瘤显像：B组：微泡剂＋低功率超声治疗前后,除肝脏部位放射性明显浓聚外,肝癌皮下瘤小鼠右侧前肢见明显放射性浓聚,用ROI技术计算比较,治疗后肿瘤部位放射性明显降低,下降46.2%.结论低功率超声辐射微泡治疗小鼠肝癌腹水转移皮下瘤,可以致肿瘤血管栓塞及抑制肿瘤细胞的增殖;67Ga ECT肿瘤显像评价低功率超声辐射微泡致肿瘤血管栓塞有一定作用.     

榄香烯对小鼠肝癌腹水瘤细胞系Hca-F25/CL-16A3的视网膜母细胞瘤抑癌蛋白及腺病毒E2启动子结合因子表达的影响

目的：探讨榄香烯对小鼠肝癌腹水瘤细胞系Hca-F25/CL-16A3治疗的作用机制。方法：将22只小鼠分成两组，对照组12只，治疗组10只。从荷瘤次日起，治疗组用榄香烯腹腔注射治疗，对照组用生理盐水治疗。20d后取瘤组织用免疫组织化学染色方法观察荷瘤小鼠两组肿瘤组织的视网膜母细胞瘤抑癌蛋白（pRB）和腺病毒E2启动子结合因子（E2F－1）蛋白的表达情况。结果：对照组肿瘤组织pRB阳性率为50％（6／12），用药组阳性率为100％（10／10），两组间差异有显著性（P＜0．05）。对照组和用药组E2F－1均呈阳性表达，表达率均为100％（12／12）和（10／10），两组间差异无显著性（P＞0．05）。结论：榄香烯对小鼠肝癌腹水瘤细胞系Hca-F25/CL-16A3有明显的抑制作用。其作用机制与pRB蛋白表达有关，与E2F－1无关。     

榄香烯抑制神经胶质瘤细胞增殖的体外研究

目的 观察榄香烯抑制神经胶质瘤细胞体外增殖的量效、时效关系。方法 采用细胞计数、MTT、H^3-TdR、集落形成试验等方法分别检测了不同细胞密度、不同药物浓度和不同作用时间榄香烯对胶质瘤细胞的作用效果。结果 榄香烯对C6、U251和SHG-44胶质瘤细胞均具有明显的抑制增殖作用。相比之下，在相同药物浓度鼠源性胶质瘤细胞C6较人源性胶质瘤细胞U251及SHG-44敏感。榄香烯对胶质瘤细胞的增殖抑制效应呈剂量依赖性，随着药物浓度和药物作用时间的增加，抑制效应增强。榄香烯能显著抑制胶质瘤细胞集落形成，当浓度达到20mg／L～40mg／L以上时，几乎完全抑制了肿瘤细胞克隆形成。结论 榄香烯能有效抑制胶质瘤细胞的体外恶性增殖。     

共刺激分子B7-2对小鼠肝癌治疗作用的实验研究

目的　应用转染有小鼠 B7- 2基因片段的肝癌细胞 ,建立小鼠肝癌模型 ,观察小鼠肿瘤生长和消退情况 ,研究共刺激分子 B7- 2对肿瘤的免疫治疗作用。方法　建立 BAL B/ c小鼠转 B7- 2基因肝癌细胞株 H2 2 / B7- 2 ,细胞计数法测定肿瘤细胞体外增殖能力 ;BAL B/ c鼠皮下接种 H2 2 / B7- 2及野生型 H2 2细胞 H2 2 / Wt,以空载体转染细胞 H2 2 / neo为对照 ,建立小鼠肝癌模型 ,观察小鼠成瘤期、荷瘤小鼠存活期及肿瘤结节大小 ;同源淋巴细胞肿瘤细胞混合培养 (MTL Cs)后测定淋巴细胞增殖指数和 CTLs活性 ,同时测定培养上清 IL- 2、IFNγ,研究 B7- 2分子的抗肿瘤免疫效果。结果　细胞在体外增殖能力一致 (P= 0 .782 ) ;当接种不同肿瘤细胞后 ,三组动物都发生肿瘤 ,接种 H2 2 / B7- 2组肿瘤形成有迟发性 ,并在接种 18d后肿瘤都开始缩小 ,但最终不会完全消失 ;接种 H2 2 / Wt和 H2 2 / neo组动物肿瘤都开始缩小 ,但最终不会完全消失 ;接种 H2 2 / Wt和 H2 2 /neo组动物肿瘤呈进行性生长。H2 2 / B7- 2在体外刺激淋巴细胞增殖和诱导 CTLs的能力明显强于对照细胞 (P<0 .0 5 )。结论　共刺激分子 B7- 2能增强肝癌细胞的免疫原性 ,它在抗肿瘤早期发挥作用。用其治疗肝癌是有效的 ,但不能介导完全和长期的抗肿瘤效应     

依那西普对磨屑诱导巨噬细胞分泌肿瘤坏死因子的影响

目的 探讨依那西普(etanercept)对人工关节无菌性松动的影响.方法 分离、培养小鼠腹腔巨噬细胞,分为5组.A组为单纯巨噬细胞组,B组为细胞 钛颗粒组,C组为细胞 钛颗粒 10ng/ml依那西普组,D组为细胞 钛颗粒 100 ng/ml依那西普组,E组为细胞 钛颗粒 1000 ng/ml依那西普组.培养18小时后,用酶联免疫吸附试验检测细胞培养上清液中肿瘤坏死因子含量.结果 A、C、D、E组肿瘤坏死因子含量明显低于B组(P＜0.001),E组肿瘤坏死因子含量明显低于C组和B组(P＜0.001).结论 磨屑可刺激巨噬细胞分泌肿瘤坏死因子,依那西普能够呈剂量依赖地有效抑制磨屑诱导的巨噬细胞分泌肿瘤坏死因子,有望成为预防人工关节无菌性松动的药物.     

Ciglitazone对裸鼠肝癌移植瘤的凋亡诱导作用及瘤细胞周期蛋白的变化

目的探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动剂c ig litazone对人肝癌细胞株H epG2体内生长的影响及机制。方法建立裸鼠肝癌动物模型,随机将其分为对照组(A组,10只)和c ig litazone实验组(B组,10只)。B组隔天注射c ig litazone 100μl(100μm o l/L)于瘤内连续15次,对照组同期注射等量生理盐水。1个月后,切除瘤灶,测量瘤灶大小,并检测肿瘤细胞周期素D 1、细胞周期素依赖性激酶抑制p21蛋白及凋亡相关蛋白caspase3的表达。结果c ig litazone治疗后,B组较对照组的生长显著延缓(P<0.05),B组的cyclinD 1较A组明显降低(P<0.05),而其的p21蛋白、凋亡蛋白caspase3表达水平较A组明显升高(P<0.05)。结论c ig litazone能抑制肝癌H epG2细胞的恶性增殖,其机制可能与PPARγ干预细胞周期和细胞凋亡有关。     

盐酸戊乙奎醚对小鼠胃肠运动及组织胃动素的影响

目的 观察盐酸戊乙奎醚对小鼠胃肠运动及组织胃动素的影响.方法 健康昆明小鼠24只,体重18～22 g,雌雄不拘,随机均分三组.盐酸戊乙奎醚组(P组)腹腔注射盐酸戊乙奎醚0.3 mg/kg,阿托品组(A组)腹腔注射阿托品0.3 mg/kg,对照组(C组)给予等容量生理盐水.各组给药15 min后以营养性半固体糊0.8 ml灌胃,20 min后处死小鼠.采用放免法测定胃动素水平；计算胃残留率和小肠推进率.结果 与A组比较,P、C组小鼠组织的胃动素浓度、小肠推进率升高；胃残留率降低(P＜0.05).结论 盐酸戊乙奎醚不抑制胃肠运动和胃动素的分泌.     

树突状细胞联合β-榄香烯治疗小鼠黑色素瘤

目的 :探讨树突状细胞 (dendriticcell,DC)联合 β -榄香烯 (β-elemene)治疗小鼠黑色素瘤的疗效。 方法 :粒 -巨噬细胞集落刺激因子 (GM -CSF)及白介素 - 4 (IL - 4 )诱导骨髓源性DC。经B1 6抗原肽致敏后制成DC疫苗 ,联合 β 榄香烯治疗荷瘤小鼠。体外观察各组脾脏T淋巴细胞IFN -γ的分泌 ;体内观察肿瘤的抑制率及生存期。 结果 :DC负载抗原后与 β 榄香烯联合治疗明显抑制荷瘤小鼠肿瘤的生长 ,使其生存期延长 ,与单纯 β -榄香烯组及对照组相比有显著差异。体外实验显示 :DC致敏组小鼠免疫应答被激活 ,其IFN -γ分泌量较对照组明显增加。 结论 :DC疫苗可激发宿主针对特异肿瘤的Th1及CTL免疫应答 ,以DC介导的免疫反应联合中药的协同作用是抗肿瘤的有效手段。     

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.