雄激素受体反义寡核苷酸对前列腺癌细胞生长的抑制作用

目的　探讨雄激素受体 (AR)反义寡核苷酸 (aODN)对前列腺癌细胞AR表达和生长的抑制作用。　方法　合成 1对AR正、反义寡核苷酸 ,与LNCaP细胞共培养 ,观察LNCaP细胞的增殖情况 ,RT PCR和Westernblot方法检测ARmRNA水平和AR蛋白表达水平。　结果　含ARaODN的培养基培养处于静止期和对数生长期的LNCaP细胞增殖较对照组均明显减慢。RT PCR证实aODN组吸光度A值 (0 .5 3± 0 .18)与ODN组 (1.14± 0 .2 1)差异有显著性意义 (P <0 .0 5 ) ,提示ARaODN可导致LNCaP细胞ARmRNA显著下调。Westernblot分析显示aODN组条带的吸光度A值 (2 6 .35± 1.33)与ODN组 (33.5 1± 1.4 8)之间差异有显著性意义 (P <0 .0 5 ) ,提示ARaODN可下调LNCaP细胞AR蛋白含量。　结论　ARaODN可抑制前列腺癌细胞AR表达并抑制前列腺癌细胞增殖。     

反义寡核苷酸阻断雄激素受体表达对前列腺癌细胞生长活性的影响

目的　探讨反义技术阻断雄激素受体 (AR)基因表达对前列腺癌细胞生长的影响。　方法　设计、合成针对AR基因反义寡核苷酸 (ASODN) ,在脂质体介导下转染前列腺癌细胞。采用RT PCR方法检测AR基因表达 ;MTT比色法检测细胞增殖活性 ;透射电镜、TUNEL检测细胞凋亡 ;流式细胞术分析细胞周期时相。　结果　 0 .5～ 2 .0 μmol LASODN作用 12～ 36h ,癌细胞ARmRNA水平降低 10 .45 %～ 82 .10 %(P <0 .0 5 ) ,细胞增殖活性抑制 11.8%～ 5 6 .9%(P <0 .0 5 ) ,细胞周期阻滞于G2 M期 ,部分细胞呈现典型凋亡形态学改变 ,凋亡比率为 34.2 5 %(P <0 .0 1)。　结论　应用ASODN封闭AR基因表达能抑制前列腺癌细胞体外生长活性 ,有望成为前列腺癌基因治疗的有效策略。     

LNCaP细胞系的雄激素非依赖性生长和类固醇尿苷二磷酸葡糖醛酯转移酶的表达

目的 :研究去除LNCaP细胞中雄激素后前列腺癌的雄激素非依赖性生长机制和葡萄糖醛酸化活性的影响。　方法 :在不含雄激素的培养基中持续传代LNCaP细胞 ,并检测细胞的葡萄糖醛酸化活性 ,以建立前列腺癌LNCaP SF的雄激素非依赖性生长模型。构建并检测尿苷二磷酸葡糖醛酯转移酶 (UGT) 2B15反义cDNA的表达载体。　结果 :LNCaP SF引起UGT2B15较高表达 ;与LNCaP细胞相比较 ,LNCaP SF的葡萄糖醛酸化活性要高 2 .5倍。LNCaP SF和LNCaP转染反义UGT2B15cDNA的能力与对照组相比更低 ,这提示UGT2B15在两种细胞雄激素萄糖醛酸化…     

熊果酸对前列腺癌细胞雄激素非依赖性的逆转作用

目的 探讨中药成分熊果酸对雄激素非依赖性前列腺癌(AIPC)的治疗作用及其机制.方法 应用熊果酸处理体外培养的人雄激素依赖性前列腺癌(ADPC)细胞株LNCaP和AIPC细胞株DU145,噻唑蓝(MTT)比色法检测细胞活性及对人工合成雄激素R1881的反应性,免疫细胞化学检测熊果酸对雄激素受体(AR)、糖皮质激素受体(GR)、前列腺特异性抗原(PSA)及成活因子HSP90和白细胞介素(IL)-6表达的影响,逆转录.聚合酶链反应(RT-PCR)检测熊果酸对DU145细胞AR mRNA表达的影响.结果 熊果酸对不同浓度雄激素下的LNCaP细胞均呈浓度和时间依赖性生长抑制,20 mg/L的熊果酸作用96 h对LNCaP细胞的抑制率近50%.0.1 nmoL/L的R1881为最适生长浓度,熊果酸作用后,LNCaP细胞生长的最适雄激素浓度上升了10倍;熊果酸对DU145细胞的生长有浓度和时间依赖性抑制效应,DU145细胞对AR阻断剂羟氟他胺缺乏反应,熊果酸作用同时再应用氟他胺比单纯熊果酸的作用更明显,对细胞抑制率明显上升.熊果酸作用后,LNCaP和DUl45细胞IL-6、HSF90表达均明显下降(P＜0.05),DU145细胞GR表达明显降低(P＜0.01),AR和PSA蛋白及AR mRNA出现再表达.结论 熊果酸能改善前列腺癌细胞对雄激素的反应性,使LNCaP细胞对雄激素的依赖性加强,并诱发了DU145细胞对雄激素的反应性,其部分机制是降低了GR、HSP90、IL-6的表达并促进AR再表达.     

抗雄激素条件下癌相关成纤维细胞对前列腺癌LNCaP细胞增殖的影响

目的体外研究抗雄激素条件下癌相关成纤维细胞(cancer associated fibroblasts,CAFs)对雄激素依赖性前列腺癌LNCaP细胞增殖能力的影响。方法体外原代培养源于人前列腺癌基质的CAFs,并用抗雄激素制剂氟他胺(Flutamide)进行处理,制备出条件培养液CAFs-Flu-CM。CAFs原代培养液制备出另一条件培养液CAFs-CM作为对照研究。观察LNCaP细胞在RPMI-1640培养液、CAFs-CM培养液和CAFs-Flu-CM培养液中的生长增殖能力和差异性。结果与RPMI-1640培养液培养的LNCaP细胞相比,10-6mol/L Flutamide可抑制其生长(76.55±7.1 vs 114.51±9.8,P<0.05);浓度为0.75g/L的CAFs-CM却可显著提高LNCaP细胞的增殖能力(237.26±18.3 vs 114.51±9.8,P<0.05)。经10-6mol/L Flutamide处理后,CAFs-Flu-CM刺激LNCaP细胞增殖的能力明显减弱(32.73±5.6 vs 237.26±18.3,P<0.05)。结论源于人前列腺癌基质的CAFs可提高LNCaP细胞的增殖能力,但经抗雄制剂处理后,CAFs功能受到干扰,刺激LNCaP细胞增殖的能力明显减弱。联合靶向CAFs的肿瘤治疗策略可能会提高前列腺癌内分泌治疗的有效性,可作为临床治疗前列腺癌新的靶点。     

苦参碱对前列腺癌细胞增殖及雄激素受体功能的抑制作用

目的:探讨苦参碱(matrine)对雄激素依赖性前列腺癌细胞株(LNCaP)的增殖及雄激素受体(androgen re-ceptor,AR)表达的抑制作用。方法:分别用0.5、1.0、1.5、2.0、3.0g/L浓度的苦参碱作用于LNCaP细胞12、24、36h后MTT法检测细胞生长活性;台盼蓝拒染法测定细胞生长曲线;24h后流式细胞仪测定细胞周期变化;24h后Western印迹法检测细胞内AR的表达。结果:苦参碱能抑制LNCaP细胞的生长,呈剂量与时间依赖性,不同浓度苦参碱组之间与不同作用时间组之间的差异均有显著性意义(P<0.01)。苦参碱诱导LNCaP细胞出现剂量依赖性G2/M期阻滞(P<0.01);细胞内AR的表达随苦参碱剂量依赖性减少(P<0.01)。结论:苦参碱通过下调细胞内AR表达和阻滞细胞周期进展来抑制LNCaP细胞的体外生长。     

前列腺组织与LNCaP细胞的雄激素受体亚型研究

目的 :研究雄激素受体 (AR)亚型在人前列腺良性增生与前列腺癌组织以及LNCaP细胞系中的表达 ,探讨AR亚型表达组织之间的差异。　方法 :应用氚标技术与聚丙烯酰胺凝胶等电聚焦电泳的方法 ,对相应组织的AR亚型进行分析。　结果 :4 1例AR阳性的前列腺增生组织、3例前列腺癌组织和LNCaP细胞中 ,发现有 3个AR亚型的表达 ,其等电点 (pI)分别在6 .5、6 .0和 5 .3。在前列腺增生标本中 ,15例 (36 .5 % )表达 pI6 .5、6 .0、5 .3亚型 ,10例 (2 4 .4 % )表达 pI6 .5、5 .3亚型 ,5例 (12 .2 % )表达 pI6 .5、6 .0亚型 ,4例 (9.8% )表达 pI6 .0、5 .3亚型 ,2例(4.9% )表达 pI6 .5亚型 ,2例 (4.9% )表达 pI6 .0亚型 ,3例 (7.3% )表达 pI5 .3亚型。在 3例前列腺癌组织中 ,1例表达pI 6 .5、6 .0、5 .3亚型 ,1例表达pI 6 .5、6 .0亚型 ,1例 3种亚型均不表达。LNCaP细胞表达pI 6 .5、6 .0、5 .3亚型。氚标的双氢睾酮 (DHT)与 3种受体亚型的结合 ,可以被非氚标的DHT、睾酮 (T)竞争抑制 ,而孕酮、雌二醇和己烯雌酚对此却无竞争抑制作用。　结论 :AR亚型的表达 ,在不同的病人与疾病和LNCaP前列腺癌细胞系之间存在差异 ,提示不同病人对前列腺癌的内分泌疗法有不同的反应性     

硼替佐米增强前列腺癌细胞对NK细胞介导细胞杀伤作用的敏感性

目的:探讨硼替佐米是否能够增强前列腺癌细胞对NK细胞介导杀伤作用的敏感性,以及是否在不同类型的人前列腺癌细胞系中有相似的作用。方法:以激素依赖性的前列腺癌细胞株LNCaP和激素非依赖性的前列腺癌细胞株DU145为模型,不同浓度(0、5、10、15、20、25nmol/L)硼替佐米处理细胞后,CCK-8法检测肿瘤细胞的增殖,Annexin V/PI法检测细胞凋亡率。结果:15、20、25nmol/L硼替佐米处理DU145细胞48、72h后,各处理组细胞的增殖率分别为(82.79±2.04)%、(73.59±2.95)%、(74.16±6.16)%和(71.24±5.30)%、(51.20±2.91)%、(38.02±2.67)%,同样处理LNCaP细胞后,各处理组细胞的增殖率分别为(77.04±7.74)%、(42.61±6.62)%、(23.85±6.04)%和(36.45±7.02)%、(14.94±5.76)%、(11.65±5.87)%。与对照组相比,硼替佐米强烈抑制两种细胞系的增殖(P0.05)。15、20、25nmol/L硼替佐米处理DU145细胞24h后,DU145细胞的凋亡率分别为(14.41±1.32)%、(16.13±1.55)%、(14.48±1.42)%,而在LNCaP细胞,20、25nmol/L硼替佐米处理24h后,凋亡率为(12.77±1.28)%和(14.84±1.65)%,与对照组相比有统计学差异(P0.05),DU145细胞对硼替佐米诱导的凋亡作用较LNCaP细胞更加敏感。但是,在短期分析中硼替佐米不能致敏两种细胞系对NK细胞介导的杀伤作用。在长效分析中,用硼替佐米处理肿瘤细胞后,20nmol/L硼替佐米+NK组诱导的DU145细胞和LNCaP细胞凋亡率分别为(41.83±5.06)%和(30.31±3.62)%,较单独应用硼替佐米或者NK细胞更高(P0.05)。结论:硼替佐米能够应用于致敏前列腺癌细胞对NK细胞介导的杀伤作用的敏感性,提高当前前列腺癌的治疗水平。而且此治疗策略对雄激素非依赖性的前列腺癌患者更有效。     

阻断雄激素受体信号后波形蛋白在前列腺癌侵袭中的表达增强

雄激素信号通路在前列腺癌生长及进展过程中发挥了重要作用。雄激素受体（AR）在绝大多数雄激素非依赖型前列腺癌中仍然表达并具有转录活性。细胞粘附与运动在多种细胞活动如细胞的分化、肿瘤的进展中起着关键作用。中间纤维波形蛋白（Vimentin）与细胞运动和侵袭相关。作者前期研究已发现利用微注射AR抗体阻断AR表达，可抑制细胞增殖并明显改变细胞形态。本文作者报道了利用雄激素敏感型的前列腺癌LNCaP细胞株、雄激素抵抗型的LNCaP—RF、     

神经内分泌分化对前列腺癌细胞生长及雄激素受体表达影响的实验研究

目的探讨神经内分泌分化对前列腺癌细胞生长的作用及对雄激素受体表达的影响。方法建立神经内分泌分化的前列腺癌细胞模型PC3MNE和LNCaPNE;采用甲基噻唑基四唑(MTT)试验观察其调节前列腺癌细胞生长的作用[以吸光度值(A)表示];采用逆转录聚合酶链反应和Western杂交方法检测LNCaPNE对LNCaP细胞雄激素受体表达的影响。结果PC3MNE的培养上清液可促进PC3M细胞的生长(A值在培养24h为034±018与050±009,48h为038±016与057±009,72h为038±015与055±005,P均<005);在有雄激素时,LNCaPNE的培养上清液不促进LNCaP细胞的生长,对其雄激素受体的表达也没有显著影响;去除雄激素后,LNCaPNE的培养上清液可促进LNCaP细胞的生长,并能下调其雄激素受体的表达(P均<005)。结论在雄激素阻断后,神经内分泌分化的前列腺癌细胞能以旁分泌的方式支持其他前列腺癌细胞生长,降低其雄激素受体的表达。     

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.