柚皮苷通过HIF-1α/VEGF信号促进H型血管抗骨质疏松的研究

目的 观察柚皮苷对去卵巢骨质疏松大鼠骨组织HIF-1α/VEGF信号通路和H型血管形成的影响,探讨柚皮苷防治骨质疏松症的作用机制。方法 建立去卵巢骨质疏松大鼠模型（随机将36只大鼠分为去卵巢组、假手术组和柚皮苷治疗组）。柚皮苷治疗３个月后,检测血清和骨髓上清骨代谢指标和HIF-1α/VEGF信号通路变化,检测骨密度(bone mineral density, BMD)、骨微结构及H型血管变化。结果 柚皮苷治疗组大鼠血清中成骨代谢指标[骨特异性碱性磷酸酶(BALP)、骨钙素(BGP)、I型原胶原分子N 端前肽(PINP)]升高;而骨吸收标志物血清C端交联肽（CTX）降低;HIF-1α在血清和骨髓上清中表达均升高;VEGF在骨髓上清中表达升高,而血清中无明显改变;BMD和Micro-CT结果显示柚皮苷治疗组大鼠骨密度和骨量增加;同时股骨近端H型血管表达升高。结论 柚皮苷可以调节骨代谢,改善骨质疏松大鼠骨密度,发挥抗骨质疏松作用,其作用机制可能是通过调节HIF-1α/VEGF信号通路、促进H型血管形成来实现的。     

葛根素诱导脂肪干细胞成骨分化的实验研究

目的观察葛根素诱导卵巢切除后骨质疏松大鼠模型的脂肪干细胞(adipose-derived stem cells,ADSCs)成骨分化的能力。方法分离、培养、传代及鉴定去卵巢骨质疏松模型大鼠ADSCs;含葛根素培养基诱导去卵巢骨质疏松大鼠ADSCs成骨分化,并测定最大有效浓度。结果去卵巢骨质疏松大鼠ADSCs成骨分化能力与加入含葛根素培养基的时间和培养基中葛根素的浓度呈正向相关,浓度为12 mmol/L时呈现无毒剂量下促进成骨分化最显著作用。结论葛根素具有较强促进去卵巢骨质疏松大鼠ADSCs成骨分化的诱导能力。     

酒精对骨髓基质细胞增殖及分化的影响

目的 观察酒精对骨髓基质细胞增殖及分化的作用．探讨骨质疏松的病理学机理。方法 以0.09mol/L酒精加入骨髓基质细胞培养物中，测定增殖的骨髓基质细胞数及培养液中骨钙素含量。通过苏丹Ⅲ脂肪细胞染色计数观察酒精作用时间对脂肪细胞分化的影响。结果 实验组骨髓基质细胞数及培养液中骨钙素含量明显低于对照组，脂肪细胞的数量随酒精作用时间延长而增多。结论 酒精抑制骨髓基质细胞增殖及向成骨方向分化，促进其向脂肪细胞分化，这可能与酒精中毒引起继发性骨质疏松时骨量减少、髓内脂肪组织增多有关。     

骨髓基质细胞成脂肪分化的研究进展

实验与临床研究证明，骨髓基质细胞成脂肪分化与骨质疏松存在着不可忽视的关系。在去卵巢或类固醇诱发的骨质疏松的动物模型均发现，骨量的丢失伴有骨髓腔内的脂肪细胞的数目大大增加。各种原因导致的骨质疏松患者中，骨髓腔内的脂肪细胞与松质骨的骨量成反比。对成纤维细胞克隆形成单位（CFU-Fs）的分析表明，9月龄大鼠骨髓中的基质干细胞数量明显少于6月龄大鼠，提示了骨髓基质细胞数量的减少和髓内脂肪细胞的增多存在某种关系。     

大豆苷元磺酸钠对维甲酸诱导大鼠骨质疏松的保护作用

目的研究大豆苷元磺酸钠对维甲酸诱导大鼠骨质疏松的保护作用。方法以70mg／kg维甲酸诱导大鼠形成骨质疏松模型。自实验开始当天下午各组大鼠依次经口给予以下药物：阴性对照组（Control）、病理模型组（Model）0．5％CMC．Na溶液5ml／kg；骨疏康组（Gsk）4g／kg；大豆苷元磺酸钠高、中、低剂量组（H．SDS300mg／kg；M-SDS150mg／kg；L-SDS75mg／kg）。连续给药5周。结果大豆苷元磺酸钠连续给药5周后，高、中剂量组骨钙素（s-BGP）均与对照组水平相当，并且可明显增加股骨骨密度；高剂量组灰重系数和骨钙含量均较模型组显著增加。高、中、低3个剂量组骨小梁形态结构趋于完整，骨髓腔呈圆形或卵圆形且腔隙较小；骨小梁面积（TS％）和平均骨小梁宽度（MTT）明显增加；骨表面平整光滑。结论大豆苷元磺酸钠对维甲酸诱导的骨质疏松大鼠的骨小梁具有保护作用，能防治维甲酸诱导的大鼠骨质疏松症。     

成骨生长肽对大鼠骨髓基质细胞增殖和成骨分化的作用

目的：观察成骨生长肽诱导体外培养的大鼠骨髓基质细胞增殖及向成骨分化的作用。方法：取6周龄SD大鼠，贴壁法分离培养骨髓基质细胞，在不同浓度成骨生长肽的诱导下，观察细胞形态变化，绘制骨髓基质细胞生长曲线，碱性磷酸酶和钙结节组织化学染色。结果：成骨生长肽对骨髓基质细胞增殖和成骨分化的作用呈剂量依赖性：成骨生长肽浓度在10^-10及10^-11mol／L时促进骨髓基质细胞增殖，而在10^-8及10^-9mol／L时对骨髓基质细胞的增殖略有抑制作用；成骨生长肽浓度在10^-10及10^-11mol／L时骨髓基质细胞碱性磷酸酶染色基本呈阴性，与对照组相比差异无统计学意义，而在10^-8及10^-9mol／L浓度下可以显著提高骨髓基质细胞碱性磷酸酶染色的阳性率。结论：成骨生长肽可以明显促进大鼠骨髓基质细胞增殖及向成骨细胞分化，其促成骨活性具有显著的浓度依赖性。     

比较不同大鼠来源骨髓基质细胞对雌激素的反应性

目的 探讨增龄和去卵巢大鼠骨髓基质细胞(BMSCs)对雌激素干预的反应.方法 取3月龄、9月龄与去卵巢(卵巢切除6月后的9月龄)SD雌性大鼠,全骨髓培养法分离培养BMSCs,传代后给予10 nM E_2干预不同时间(3、7、11、15 d).用油红O染色鉴定脂肪细胞,MTT法检测细胞的增殖能力,采用磷酸苯二钠法检测碱性磷酸酶的活性.结果 ①细胞的增殖能力随增龄和去卵巢依次递减,去卵巢组原代培养有细胞自发分化为脂肪细胞.②干预后细胞的增殖能力随时间延长逐渐增强,3月龄组和去卵巢组与相应对照组比较有显著差异.E2增强各组碱性磷酸酶活性,对去卵巢组影响更显著.结论 大鼠BMSCs的增殖和分化能力随增龄和去卵巢下降,雌激素促进大鼠BMSCs的增殖和成骨分化,3月龄组和去卵巢组细胞对雌激素更敏感.     

脉冲电磁场对卵巢切除大鼠骨质疏松的预防作用

目的:观察脉冲电磁场(PEMFs)对去势后大鼠骨质疏松症的预防作用.方法:40只雌性SD大鼠随机分为5组:去势组、对照组和3个PEMFs治疗组.治疗组磁场强度分别为2、4和8G,每天治疗6h,共12周.术后12周处死动物,测定血清骨钙素、骨密度、生物力学参数、骨形态计量学分析.结果:PEMFs治疗可以提高骨密度、骨小梁面积百分比、骨小梁宽度、骨小梁数目和股骨生物力学性能.PEMFs还可以降低去势后升高的血清骨钙素.结论:PEMFs治疗可以预防大鼠卵巢切除引起的骨质疏松.     

音猬因子修饰的骨髓间充质干细胞治疗大鼠骨质疏松的实验研究

目的探讨转染音猬因子的骨髓间充值干细胞移植对卵巢切除骨质疏松大鼠的治疗作用。 方法选取40只雌性SD大鼠，分为假手术组、模型组、骨髓间充值干细胞（BMSCs）移植组和音猬因子修饰的骨髓间充值干细胞（Shh-BMSCs）移植组，每组10只动物。假手术组手术中仅摘除卵巢附近的脂肪组织，但不摘除卵巢。其余的3组均进行双侧的卵巢切除手术，建立骨质疏松模型，在骨质疏松造模后的2个月，BMSCs移植组和Shh-BMSCs移植组分别通过大鼠的尾静脉注射BMSCs与Shh-BMSCs（第四代，约2*10⁶个干细胞），模型组动物注射等量PBS液体。在干细胞移植2 w后，检测尾静脉中血清钙、磷、碱性磷酸酶水平，同时采用双能X射线骨密度仪测量大鼠的股骨、腰椎及全身骨密度，micro-CT扫描进行胫骨的形态计量学指标分析。 结果（1）与假手术组相比，模型组的大鼠骨小梁厚度、骨小梁数量和骨体积分数均明显减少，大鼠的骨密度、血清钙与碱性磷酸酶明显降低，而大鼠的血清磷水平明显升高，差异有统计学意义（P<0.05），以上表明骨质疏松大鼠模型成功制备。（2）与模型组相比，BMSCs组的大鼠血清钙和和碱性磷酸酶明显升高，而血清磷水平明显降低，差异有统计学意义（P<0.05）。与模型组、BMSCs组相比，Shh-BMSCs组大鼠血清钙、碱性磷酸酶水平明显升高，而血清磷水平明显降低，差异有统计学意义（P<0.05）。（3）同模型组的骨密度相比，BMSCs组大鼠的骨密度明显升高，差异有统计学意义（P<0.05）；与模型组、BMSCs组相比，Shh-BMSCs组大鼠的骨密度明显升高，差异有统计学意义（P<0.05）。（4）同模型组相比，BMSCs组的大鼠骨小梁厚度、骨小梁数量和骨体积分数均明显增加，差异有统计学意义（P<0.05），与模型组和BMSCs组相比，Shh-BMSCs组的大鼠骨小梁厚度、骨小梁数量和骨体积分数均明显增加，差异有统计学意义（P<0.05）。 结论Shh-BMSCs细胞移植后能够治疗大鼠卵巢切除后的骨质疏松。     

锶盐对骨质疏松大鼠骨微结构的影响

目的 探讨锶盐对去势骨质疏松大鼠骨微结构的影响.方法 采用11个月龄Wiatar雌性大鼠,随机分成假手术(Sham)组、卵巢切除(OVX)组和卵巢切除加锶盐(Sr)组.于手术1周后,Sham组和OVX组大鼠给予生理盐水口服,Sr组则给予锶盐口服[SrCl2,250 ms/(kg·d)],持续12周.第13周时,取近端胫骨行微焦点计算机断层扫描(micro computed tomography,micro CT)检测骨微结构,骨组织形态计量学方法评价锶盐对大鼠骨质疏松的骨重建的影响.结果 micro CT提示与去势组相比,实验组大鼠骨小梁体积、骨小梁厚度均明显增加(P<0.05),而骨小梁间距明显减少(P<0.05).静态和动态骨组织形态计量学均表明锶盐可明显提高骨重建过程骨形成而降低骨吸收的作用.结论 锶盐可以促进去卵巢大鼠骨重建过程中的骨形成参数而降低骨吸收的参数,改善雌激素减少导致的骨小梁微结构的退变,这可能是锶盐降低绝经后骨质疏松患者骨折风险的基础.     

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.