二氢青蒿素通过线粒体依赖性途径诱导人胃癌细胞凋亡的机制

目的 探讨二氢青蒿素(DHA)体外诱导人胃癌SGC7901细胞凋亡的分子作用机制.方法 体外培养人胃癌SGC7901细胞,不同浓度(6.25、12.50、25.00、50.00、100.00μmol/l) DHA作用24、48、72 h后,噻唑蓝(MTT)比色法检测细胞增殖;DHA作用人胃癌SGC7901细胞24 h后,流式细胞仪检测细胞凋亡率;分光光度法检测细胞半胱氨酰大冬氨酸特异性蛋白酶3(Caspase-3)和Caspase-9活性变化;线粒体膜电位检测试剂盒(JC-1)荧光染色检测线粒体膜电位(△Ψm)的改变;Western blot法分别测定B-细胞淋巴瘤/白血病-2(bcl-2)和bax蛋白的表达水平;Western blot检测胞质中细胞色素C( Cyto C)的含量变化.结果 DHA对SGC7901细胞增殖抑制具有明显量效和对效关系;与对照组(1.88±0.25)比较,不同浓度DHA作用人胃癌SGC7901细胞24h后,细胞凋亡率[(4.21±0.83)％、(6.92±1.26)％、(9.78±2.55)％、(13.93±2.94)％、(16.02±3.83)％]明显增加(P＜0.05);与对照组(0.091±0.007、0.079±0.006、100.000±0.000)比较,Caspase-3(0.094±0.008、0.196±0.014、0.288±0.017、0.326±0.024、0.491±0.042)和Caspase-9 (0.082±0.008、0.154±0.010、0.176 ±0.012、0.217 ±0.015、0.268±0.024)活性逐步升高(P＜0.05);△Ψm( 74.18±7.84、70.08±6.53、58.66±2.38、48.79±1.31、31.24±0.73)逐渐下降(P＜0.05);不同浓度DHA处理组bax蛋白表达逐渐升高(p＜0.05),bcl-2表达逐步下降(P＜0.05),bcl-2/bax比值(2.37±0.24、1.51±0.21、0.82±0.16、0.64±0.14、0.37±0.07)显著降低,与对照组(3.11±0.28)比较有剂量依赖趋势(P＜0.05);与对照组(0.18±0.04)比较,不同浓度DHA均能剂量依赖地诱导胞质Cyto C表达(0.21±0.05、0.25±0.06、0.38±0.08、0.39±0.09)增加(P＜0.05).结论 DHA具有促进胃癌细胞凋亡的作用,且有剂量依赖的趋势,其机制与线粒体凋亡途径有关.     

二甲双胍对人胰腺癌细胞增殖与凋亡的影响及其分子机制的研究

目的 研究二甲双胍在体外对人胰腺癌细胞BxPC 3、AsPC 1生长增殖、凋亡的影响及其抗肿瘤相关分子机制.方法 体外培养人胰腺癌BxPC-3、AsPC 1细胞,四甲基偶氮唑盐(MTT)法检测二甲双胍在不同浓度和不同时间对于胰腺癌细胞增殖的影响,并计算IC50值.用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定(TUNEL)法检测处理后细胞的凋亡情况.RT-PCR法检测COX-2、bcl-2、Survivin的表达影响.结果 MTT法检测显示,不同浓度二甲双胍均可抑制BxPC-3、AsPC-1两种人胰腺癌细胞增殖,两种胰腺癌细胞IC50分别为68.882 mmol/L和90.984 mmol/L.TUNEL法检测人胰腺癌细胞BxPC-3,正常对照组及二甲双胍干预组(以1/2 IC50浓度处理胰腺癌细胞)凋亡率分别为(2.44±0.57)％和(17.52±0.75)％,P＜0.05;胰腺癌细胞AsPC-1在正常对照组及二甲双胍干预组凋亡率分别为(5.35±0.92)％和(45.76±1.87)％,P＜0.05.RT-PCR结果显示:人胰腺癌细胞BxPC-3在正常对照组及二甲双胍干预组COX-2的mRNA灰度值分别为0.769±0.006和0.305±0.009,P＜0.05; bcl-2的mRNA灰度值分别为0.401±0.022和0.129±0.010,P＜0.05;Survivin的mRNA灰度值分别为0.943±0.029和0.143±0.050,P＜0.05.人胰腺癌AsPC-1细胞在正常对照组及二甲双胍干预组COX-2的mRNA灰度值分别为1.232±0.011和0.831±0.022,P＜0.05;bcl-2的mRNA灰度值分别为0.400±0.053和0.129±0.032,P＜0.05;Survivin的mRNA灰度值分别为0.983±0.017和0.174±0.029,P＜0.05.结论 二甲双胍抑制胰腺癌细胞增殖、促进凋亡.二甲双胍抗肿瘤机制可能是通过抑制COX-2、bcl-2及Survivin的mRNA表达来实现的.     

力学刺激对软骨细胞凋亡信号转导分子Caspase-3及bcl-2、bax mRNA表达的影响

目的 观察力学刺激对软骨细胞凋亡信号转导分子半胱氨酸酶-3( Caspase-3)及B细胞淋巴瘤-2(bcl-2)、bax mRNA表达和凋亡的影响.方法 兔膝关节软骨分离培养,在第3代软骨细胞培养瓶中加入不同剂量的Caspase-3、bcl-2、bax抑制剂,力学刺激诱导凋亡,然后检测软骨细胞凋亡率,聚合酶链反应(PCR)半定量分析Caspase-3 bcl-2、bax mRNA表达.结果 力学刺激诱导软骨细胞凋亡,在加入抑制剂的各组和空白组的凋亡率差异有统计学意义(P＜0.05);各组Caspase-3及bcl-2、bax mRNA表达和空白组差异有统计学意义(P＜0.05).Caspase-3抑制剂组的凋亡率和Caspase-3表达明显相关(r=0.69,t=3.41,P＜0.01);bcl-2抑制剂组和bcl-2的表达明显相关(r=0.73,t=3.97,P＜0.01);bax抑制剂组和bax的表达明显相关(r=0.89,t =6.69,P＜0.01);各组差异均有统计学意义.结论 Caspase-3、bax抑制剂能对抗力学刺激诱导的凋亡,而bcl-2抑制剂使凋亡增加,各组Caspase-3及bcl-2、bax mRNA表达发生相应改变.     

氧化苦参碱对人非小细胞肺癌A549细胞凋亡的影响及其机制

目的 观察氧化苦参碱(OXY)对人非小细胞肺癌A549细胞凋亡的影响并探讨其机制.方法 噻唑蓝(MTT)法测定OXY对A549人肺癌细胞活力的作用.流式细胞术测定A549细胞凋亡率.荧光定量聚合酶链反应(FQ-PCR)和Westem blot方法测定OXY对A549细胞B淋巴细胞/白血病-2(bcl-2)、bcl-2相关X蛋白(bax) mRNA和蛋白表达的影响.Western blot方法测定OXY对A549细胞的细胞外信号调节蛋白激酶(ERK)、c-Jun氨基端激酶(JNK)、p38丝裂原活化激酶(p38MAPK)、磷酸化ERK(p-ERK)、p-JNK、p-p38 MAPK蛋白表达的影响.结果 OXY可抑制A549细胞增殖.与对照组[(5.63±0.76)％]比较,OXY组细胞凋亡率[(13.26±2.15)％]上升(P＜0.01);与对照组(1.02±0.27、0.23±0.04)比较,OXY组bax mRNA(1.61±0.19)和蛋白(0.71±0.10)表达上升(P＜0.05,P＜0.01);与对照组比较(0.94 ±0.14、0.64±0.09),OXY组bcl-2mRNA(0.42±0.05)和蛋白(0.21±0.04)表达下降(P＜0.01).与对照组(0.29±0.03)比较,OXY组p-JNK表达水平(0.66 ±0.06)明显升高(P＜0.01),其他蛋白表达均无明显变化.与OXY组(0.66±0.07、0.28±0.03、0.65±0.08)比较,同时给予OXY和p-JNK抑制剂SP600125组bax蛋白表达(0.39±0.05)下降,bcl-2表达(0.50±0.08)上升,p-JNK蛋白(0.26 ±0.04)表达下降(P＜0.01).结论 OXY碱可诱导A549细胞凋亡,可能与升高p-JNK水平有关.     

急性胰腺炎大鼠肾上腺损伤中bax与bcl-2表达的研究

目的 观察急性胰腺炎(AP)大鼠肾上腺损伤时细胞凋亡及调控基因bcl-2和bax蛋白的表达及作用.方法 采用牛磺胆酸钠逆行胰胆管注射法建立AP模型.术后3、6、12 h检测血皮质酮水平,观察肾上腺病理,TUNEL检测细胞凋亡,免疫组织化学检测bcl-2和bax蛋白表达.结果 与SO组比较,AP3 h组血清皮质酮显著增高,随后逐渐降低(P＜0.05).随病程延长,肾上腺细胞凋亡指数增高,bax蛋白表达增强,bax/bcl-2比值亦逐渐升高(P值均＜0.05),并与凋亡指数(AI)呈正相关(r =0.759,P＜0.05).结论 bax和bcl-2可能参与了AP肾上腺损伤的发病过程.通过激活bcl-2和抑制bax的蛋白表达,减少细胞凋亡发生从而保护肾上腺结构和功能,可能为今后AP及相关肾上腺损伤的药物及基因治疗提供依据和新思路.     

白花蛇舌草诱导人胶质瘤细胞凋亡的作用及机制

目的 探讨白花蛇舌草诱导胶质瘤U87细胞株凋亡的作用及机制.方法 采用不同浓度的白花蛇舌草含药培养基(0、100、200 ml/L)处理U87细胞48 h,流式细胞仪检测对照组与实验组细胞的凋亡率及线粒体膜电位差异,Western blot法检测两组细胞中抗凋亡基因[B细胞淋巴瘤/白血病-2(bcl-2)]和促凋亡基因(bax)的表达水平改变.结果 经100、200 ml/L白花蛇舌草处理的U87细胞凋亡率明显增加,分别为(17.31±1.36)％、(41.23±0.72)％,明显高于对照组的(8.11±1.71)％(P＜0.01),呈显著的剂量依赖性;经JC-1染色法处理后,呈绿色荧光的U87细胞比率随含药培养基浓度升高而增多,分别为(11.90±0.20)％、(34.17±2.79)％,明显高于对照组的(5.53±1.20)％(P＜0.05),提示其线粒体膜电位受药物影响而逐步递减;白花蛇舌草能显著上调促凋亡蛋白bax基因的表达并降低bcl-2/bax比率.结论 白花蛇舌草通过线粒体依赖性途径诱导人胶质瘤U87细胞的凋亡.     

曲古抑菌素A诱导胰腺癌细胞株凋亡和Notch信号通路改变的研究

目的 研究曲古抑菌素A(Trichostatin A,TSA)干预对胰腺癌细胞株PANC-1凋亡及相关基因表达的影响,探讨其作用机制.方法 采用0.1 ～0.4 μmol/L不同浓度TSA处理胰腺癌细胞.四甲基偶氮唑蓝(MTT)法检测各组细胞的存活率,通过Hoechst 33258染色直接观察细胞凋亡.实时荧光定量PCR(RT-qPCR)方法检测包括Notch信号通路相关的基因、肿瘤增殖相关基因eaf2和肿瘤转移相关基因cytohesin 1、2、3、4的表达.蛋白质印迹法检测细胞caspase-3、bcl-2、bax以及Notch-1的胞内活性形式NICD蛋白表达.结果 TSA对PANC-1的增殖抑制作用呈明显浓度和时间依赖性,0.1、0.2、0.4 μmol/L TSA作用PANC-1 24 h后存活率分别为72％、58％和39％.显微镜观察发现随着TSA浓度增加和作用时间延长,PANC-1细胞死亡逐渐增加,Hoechst 33258染色可见凋亡典型特征的PANC-1细胞比例增加.TSA作用PANC-1后,蛋白质印迹法结果显示caspase-3、bax以及NICD蛋白表达增加,而bcl-2蛋白表达下降.qRT-PCR结果显示Notch通路中相关基因numb、hes6mRNA表达升高,gcn512、dll3 mRNA表达下降(P＜0.05),而Notch1 mRNA表达没有变化.肿瘤增殖相关基因eaf2以及肿瘤转移相关基因cytohesin mRNA表达未发现有变化(P＞0.05). 结论 TSA可诱导胰腺癌PANC-1细胞凋亡,且呈剂量依赖性.Notch通路相关基因可能参与了TSA诱导细胞凋亡的过程.     

灯盏细辛对大鼠肾冷缺血再灌注损伤中细胞凋亡的影响

目的 观察中药灯盏细辛对大鼠肾脏冷缺血再灌注损伤(IRI)中肾脏细胞凋亡及相关基因表达的影响.方法 封闭群SD大鼠36只,随机分为3组,每组12只.假手术组(A组),对照组(B组),实验组(C组).药物应用:C组术前15 min,灯盏细辛注射液按1.2 ml/100 g通过尾静脉注射,A、B组按相应剂量注射生理盐水.动物手术:A组,切除右肾.B、C组采用的是冷IRI模型,3组大鼠均在术后24h再次手术切除左肾进行检测.透射电镜检查肾组织形态学,免疫组织化学检测凋亡相关的基因bcl-2与bax的表达,原位末端标记法(TUNEL)检测细胞凋亡.结果 (1)超微结构检查(透射电镜):A组结构正常;B组细胞呈损伤形态:线粒体肿胀,微绒毛减少,胞质内空泡形成,部分细胞核可见凋亡迹象.C组病变较B组显著减轻.(2)免疫组织化学蛋白阳性染色指数(PI):缺血再灌注后B、C组的bcl-2表达分别为(21.21±1.18)％和(35.52±1.94)％,较A组(4.95±0.77)％均增多(P＜0.05),B组低于C组(P＜0.05).B、C组的bax表达分别为(58.55±2.90)％和(45.90±3.14)％,较A组(4.67±0.67)％增多(P＜0.05),而且B组高于C组(P＜0.05).A组的蛋白阳性染色指数的比值bcl-2/bax为(1.06±0.07)高于B组(0.35±0.03)和C组(0.78±0.07,P＜0.05),而且C组高于B组(P＜0.05).(3)细胞凋亡检测(TUNEL):细胞凋亡指数B组(28.57±3.58)％和C组(19.99±3.37)％均显著大于A组(2.33±0.42)％(P＜0.01),C 组小于B组(P＜0.01).结论 灯盏细辛减少大鼠肾脏冷IRI诱导的肾脏细胞的凋亡,与调节凋亡相关基因bcl-2与bax表达有关.     

WWOX表达对胆管癌QBC939细胞凋亡的影响及其机制

目的 探讨含有WW结构域的氧化还原酶基因(WWOX)表达对胆管癌QBC939细胞凋亡的影响及其作用机制.方法 用脂质体转染法将WWOX重组真核表达质粒转染QBC939细胞;采用荧光定量逆转录－聚合酶链反应(RT-PCR)和Westem blot法鉴定WWOX在QBC939细胞中的表达;流式细胞仪(FCM)法检测转染前后各细胞凋亡率的变化;JC-l染色法检测细胞线粒体膜电位(△Ψm)变化;荧光定量RT-PCR和Western blot法检测胆管癌细胞bcl-2表达的变化;将未转染和转染空质粒的细胞作为对照组接种到裸鼠皮下以检测荷瘤,TUNEL方法原位检测移植瘤的凋亡.结果 建立了稳定表达WWOX基因的QBC939/WWOX细胞株,mRNA及蛋白表达明显增加.FCM显示QBC939/WWOX组的细胞凋亡率明显增高[(1.24±0.35)％比(1.73±0.48)％比(21.40±2.35)％,P＜O.01],JC-l显示转染组的线粒体膜电位下降[(4.27±0.64)％比(4.96±0.52)％比(28.60±3.94)％,P＜O.01],bcl-2 mRNA及蛋白的表达均显著降低(P＜0.05).转染组的皮下肿瘤较对照组生长速度明显减慢(P＜0.05),TUNEL实验证实转染组的皮下肿瘤凋亡指数为(13.6±1.5)％,较对照组明显增高,差异有统计学意义(P＜0.O1).结论 WWOX基因能促进胆管癌细胞的凋亡,其机制可能与下调bcl-2的表达,激活线粒体凋亡通路有关.     

术前介入动脉化疗对胰腺癌细胞凋亡和细胞增殖的影响

目的检测术前选择性介入动脉化疗对胰腺癌细胞凋亡和细胞增殖的作用,探讨区域性化疗抑制胰腺癌生长的分子机制.方法采用原位末端标记法(ISEL)对32例术前行介入化疗和未化疗的胰腺癌患者的病理切片进行细胞凋亡指数和增殖指数的检测,同时测定细胞凋亡调控基因bcl-2和bax的表达水平.结果(1)术前介入化疗组胰腺癌细胞凋亡率比未介入化疗组明显增高,两组的细胞凋亡率分别为(46.89±26.46)和(5.67±2.43)(P＜0.01);而细胞增殖指数(PCNA)在术前介入化疗组与非化疗组之间无显著差异(P＞0.05).(2)肿瘤细胞凋亡率与组织类型有关,高分化腺癌中的细胞凋亡率比低分化腺癌高(P＜0.05).(3)术前介入化疗组bcl-2表达率低于未介入化疗组,bax表达率高于未介入化疗组(P＜0.05).结论术前选择性的动脉介入化疗能够诱导胰腺细胞凋亡,诱导细胞凋亡是抑制胰腺癌细胞的生长重要途径.     

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.