Notch1在邻苯二甲酸二丁酯致大鼠尿道下裂发生中的表达

目的:利用邻苯二甲酸二丁酯(DBP)胚胎期暴露诱导子代SD大鼠发生尿道下裂,检测Notch1在尿道下裂胎鼠与正常胎鼠生殖结节(GT)中的差异表达,探讨其在DBP致大鼠尿道下裂发生中的作用。方法:SD孕鼠20只,随机分为两组,实验组和对照组各10只。妊娠(GD)14～18 d,实验组和对照组分别给予DBP 800 mg/(kg.d)和大豆油2 ml/(kg.d)灌胃,孕第19天剖宫产后记录雄性胎鼠出生体重(BW)、肛门和生殖器之间的距离(AGD)及尿道下裂发生率。取DBP组中发生尿道下裂的雄性胎鼠和对照组中的雄性胎鼠,分为尿道下裂组与对照组,提取生殖结节,用Western印迹法和免疫组化法分析Notch1的表达。结果:实验组子代雄性胎鼠体重为(4.40±0.30)g,对照组为(6.11±0.40)g,实验组较对照组明显下降(P<0.05);实验组AGD为(2.17±0.18)mm,对照组为(3.28±0.16)mm,实验组较对照组明显缩短(P<0.05),尿道下裂发生率为42.9%。Notch1在尿道下裂组的相对表达量为0.671±0.021,正常对照组为1.327±0.031,差异有统计学意义(P<0.05);Notch1主要定位于生殖结节上皮细胞,尿道下裂组染色强度明显弱于对照组。结论:染毒期间DBP对雄性子鼠有明显毒性作用,改变了生殖结节中Notch1的表达,可能影响细胞的增殖和凋亡及上皮-间质转化(EMT),导致尿道下裂的发生。     

邻苯二甲酸二丁酯致尿道下裂大鼠发育异常和阴茎病理学改变研究

目的邻苯二甲酸二丁酯（DBP）孕晚期染毒诱导子代雄鼠尿道下裂发生和探讨DBP致尿道下裂雄鼠发育异常和阴茎病理学改变。方法雌鼠怀孕14～18d，每天分别灌胃给予大豆油（A组），DBP500（B组）、800（C组）、1200（D组）mg／kg体重，分娩后统计仔鼠数和雄仔鼠体重。出生后（PND）7d测量雄仔鼠肛门生殖器距离（AGD），观察尿道下裂发生率和尿道下裂阴茎病理学改变。PND70,对尿道下裂雄仔鼠称重后解剖，评价发育情况。结果C组仔鼠数和雄仔鼠体重明显减少；D组出现孕鼠死亡和零产仔；尿道下裂仅C组发生。发生率为36．5％。PND7，B、C组雄仔鼠AGD和A组相比明显减小。阴茎连续性病理切片显示典型尿道下裂改变。解剖得尿道下裂雄仔鼠肝、肾、前列腺、睾丸、附睾脏器系数与A组相比明显减小，脑垂体脏器系数明显增大。结论800mg／kg体重DBP孕晚期染毒能高诱导雄仔鼠尿道下裂发生，DBP不仅损害雄仔鼠生殖系统，还引起发育异常。     

邻苯二甲酸二丁酯诱导尿道下裂大鼠模型的建立及其作用机制

目的用邻苯二甲酸二丁酯(DBP)诱导建立尿道下裂大鼠模型并在分子水平研究其导致尿道下裂的作用机制。方法将孕鼠在怀孕第12～19天用DBP(500mg/kg体重)连续每天灌胃建立仔代雄鼠尿道下裂模型，并将孕鼠在第19天行破宫产取仔代雄鼠的睾丸组织，用逆转录一聚合酶链反应(RT-PCR)的方法检测睾酮合成过程中限速酶细胞色素P450胆固醇侧链裂解酶(P450scc)、3p羟基类固醇脱氢酶(3p-HSD)和细胞色素P45017α-羟化酶(P450c17)的mRNA含量水平，与正常对照组进行比较。结果DBP诱导的尿道下裂组胎鼠睾丸组织中P450scc、3β-HSD和P450c17的基因表达水平较正常对照组均有不同程度的下降，两组间差异比较均有统计学意义(P＜0．05)。结论DBP通过在性发育期干扰仔代雄鼠睾丸组织中睾酮的生物合成途径，降低了睾酮水平，导致大鼠出生后尿道下裂的出现。     

DEHP对宫内仔鼠睾酮水平、IGF-1和 StAR mRNA表达的影响

目的 探讨不同剂量的邻苯二甲酸二(乙基)己酯(DEHP)对宫内期仔鼠睾酮水平及胰岛素样生长因子1(IGF-1)、类固醇激素合成急性调节蛋白(StAR)基因表达的影响.方法 雌性S-D大鼠24只,随机均分为4组:正常组、低剂量组、中剂量组和高剂量组.后三组给予不同剂量的DEHP灌胃,剂量分别为(10mg/kg·d-1)、(100mg/kg·d-1)、和(750mg/kg·d-1),时间自雌鼠怀孕后第一天开始至仔鼠出生后第一天止.正常组给予等剂量的玉米油.测量各组雄仔出生时肛门生殖器距离(AGD)和血清睾酮(T)水平;并用光镜和电镜观察仔鼠睾丸Leydig细胞形态学改变;Real-timePCR检测睾丸组织中IGF-1和StARmRNA表达水平.结果 与正常组比较,高剂量组AGD明显缩短,中剂量组AGD呈下降趋势;低剂量组T水平升高、中高剂量组T水平降低;低、中、高剂量组StARmRNA表达下降;低剂量组IGF-1mRNA表达升高,中、高剂量组表达下降.光镜下见随着剂量的升高,睾丸Leydig细胞聚集越明显,高剂量组Leydig细胞呈瘤样聚集;电镜下见低剂量组Leydig细胞线粒体和滑面内质网增多,中、高剂量组均减少,并见脂滴增加.结论 DEHP可以影响富内仔鼠睾酮的合成,不同剂量具有不同的效应,其机制可能与DEHP影响IGF-1和StARmRNA表达有关.     

双氢青蒿素对前列腺癌细胞PC-3M生长的影响及其机制探讨

目的:观察双氢青蒿素对雄激素非依赖性前列腺癌细胞株PC-3M细胞凋亡和血管内皮生长因子(VEGF)表达的影响。方法:不同浓度(0、25、50、100μmol/L)的双氢青蒿素分别作用于PC-3M细胞48 h,MTT法检测细胞生长活性;流式细胞仪测定细胞凋亡率;分光光度法检测细胞凋亡过程中caspase-3、caspase-8活性变化;半定量RT-PCR法检测PC-3M细胞内VEGF mRNA的表达;Western印迹法检测细胞VEGF蛋白表达。结果:双氢青蒿素能显著抑制PC-3M细胞的增殖,与对照组(0μmol/L)的细胞凋亡率(2.92±0.45)%相比,各剂量组(25、50、100μmol/L)的细胞凋亡率[(8.85±0.74)%,(12.83±0.84)%,(18.65±1.24)%]显著增加,caspase-8[(0.47±0.05)U/μg vs(1.22±0.15)U/μg,(1.76±0.07)U/μg,(2.91±0.24)U/μg]、caspase-3[(0.44±0.07)U/μg vs(0.95±0.08)U/μg,(1.48±0.14)U/μg,(2.92±0.45)U/μg]活性显著增加,呈剂量依赖性(P<0.01)。PC-3M细胞内VEGF mRNA的表达和蛋白表达呈剂量依赖性降低。结论:双氢青蒿素能显著抑制体外PC-3M细胞的生长,并促进其凋亡,机制可能与增加凋亡蛋白酶和抑制VEGF表达有关。     

尿道下裂大鼠模型的建立及莠去津对大鼠尿道下裂发病率的影响

目的建立SD大鼠尿道下裂动物模型,探讨莠去津对大鼠尿道下裂的发病率有无影响。方法将受孕的SD大鼠120只,随机分为6组,每组20只。于孕期第11～16天时,每天分别给予莠去津25mg/kg、莠去津100mg/kg、莠去津200mg/kg、植物油1ml/kg、非那雄胺10mg/kg、非那雄胺20mg/kg。给药后即刻观察并记录动物的反应情况,于孕期第0、3、6、9、12、15、18、20天称重以调整剂量。于仔鼠出生后第21天,检测其有无尿道下裂,并记录其肛生殖窦距离及其体重。结果200mg/kg莠去津组、10mg/kg非那雄胺组、20mg/kg非那雄胺组仔鼠出生时尿道下裂发生率分别为10.23%、28.30%、67.03%;25mg/kg莠去津组中有2只母鼠的胚胎着床后发育停滞。各组雄性仔鼠的肛生殖窦距离（AGD）与其体重存在正相关关系。结论①大鼠仔鼠尿道下裂表现为阴茎头和（或）阴茎腹侧裂开、尿道口异位,并有肛生殖窦距离的变窄,SD大鼠孕期第11～16天管饲每天10mg/kg及20mg/kg非那雄胺,可以建立尿道下裂动物模型。②莠去津对SD大鼠是一种胚胎致畸物。     

氯化镉对雄性小鼠的生殖毒性作用

目的研究氯化镉对雄性小鼠生殖器官和生殖细胞的毒性作用以及对雄性小鼠生殖功能的影响。方法分别以每公斤体重0..5mg/kg、2mg/kg、8mg/kg体重腹腔染毒4周龄雄性小鼠,共10次。第50天以雌雄2:1同笼交配,观察雌鼠受孕率、生育子胎数、胎鼠重量。同时观察染毒雄鼠第50天时睾丸发育和睾丸指数、附睾精子数量、精子活动率和精子畸形率以及生殖细胞减数分裂。结果2mg/kg和8mg/kg组染毒小鼠睾丸发育受到影响,睾丸指数显著低于对照组和0.5mg/kg组(p<0.05,p<0.001)。2mg/kg组中部分小鼠(6/11)和8mg/kg组存活小鼠睾丸发育不良,无精子,不育。2mg/kg组小鼠1周受孕率和3周受孕率显著低于对照组和0.5mg/kg组(p<0.05),但染毒组异常妊娠率与对照组比差异无显著性。0.5mg/kg组雄鼠生育力、附睾精子数量、精子活动率和精子畸形率与对照组比较差异无显著性。结论2mg/kg浓度和更高浓度氯化镉致4周龄雄鼠睾丸发育不良,导致无精子症和不育,是造成生殖力降低的主要原因。     

半乳糖凝集素-3在邻苯二甲酸二丁酯致大鼠尿道下裂发生中的表达

目的 利用邻苯二甲酸二丁酯(DBP)胚胎期暴露导致SD大鼠尿道下裂发生的动物模型,观察半乳糖凝集素-3(galectin-3)在尿道下裂与正常大鼠生殖结节中的差异表达,探讨其在DBP致大鼠尿道下裂发生中的作用.方法 SD孕鼠20只,随机分为2组,妊娠14～18 d(GD14～18)实验组和对照组分别给予DBP 800 mg/(kg·d)和大豆油2 ml/d灌胃,GD19剖宫产后统计子鼠数、雄性子鼠出生体质量(BW)及肛门生殖器距离(AGD)、尿道下裂发生率,取两组雄性子鼠生殖结节,运用免疫印迹法和免疫组织化学方法分析galectin-3的表达.结果 尿道下裂仅实验组发生,发生率为40%,每窝子鼠数、雄性子鼠BW及AGD/BW在实验组分别为(8.90±1.25)只、(5.12±0.24)g、(0.57±0.03)mm/g,在对照组分别为(13.20±1.46)只、(6.72±0.42)g、(0.66±0.07)mm/g,差异有统计学意义(P＜0.05);galectin-3在尿道下裂组的相对表达量为0.603±0.014(n=10),正常对照组为0.851±0.015(n=10),差异有统计学意义(P＜0.05);galectin-3主要定位于生殖结节上皮细胞,尿道下裂组染色强度明显弱于对照组.结论 染毒期间DBP对雄性子鼠有明显毒性作用,改变了生殖结节中galectin-3的表达,影响了上皮细胞增殖、凋亡及尿生殖褶的融合.     

青春期前己烯雌酚暴露对SD大鼠睾丸发育及功能的影响

目的:研究青春期前己烯雌酚(DES)暴露对SD大鼠睾丸发育及功能的影响。方法:21日龄雄性SD大鼠90只,随机分为DES0.01、0.1、1.0、10.0μg/(kg.d)4个实验组和1个对照组(分别为Da、Db、Dc、Dd和C组,每组n=18)。于青春期前,即出生后第22d(postnatalday22,PND22)～35d(PND35),实验组每日皮下注射相应剂量的DES,共14d,对照组仅注射溶媒(玉米油)。观察各组大鼠睾丸下降时间。于青春期晚期(PND50)、性成熟后(PND64)和成年期(PND130)分3批(每批n=6)处死各组大鼠取材,测定睾丸重量,观察比较睾丸组织形态学变化,分析PND130大鼠附睾尾精子质量。结果:C、Da、Db、Dc和Dd组睾丸下降时间分别为PND26.17±1.94、26.83±1.47、28.68±1.03、33.50±1.87和41.50±2.74,其中Db、Dc和Dd组较C组明显延迟(P<0.05或P<0.01)。PND50时,C、Da、Db、Dc和Dd组单侧睾丸重量分别为(1.38±0.10)、(1.38±0.12)、(1.30±0.14)、(0.86±0.18)g和(0.73±0.27)g,其中Dc和Dd组较C组显著减轻(P<0.01);与C组比较,Db组仅有少数生精小管生精上皮中的细胞数目稍减少,Dc和Dd组生精小管发育较差、生精上皮中细胞数目减少、精子发生阻滞、间质细胞发育幼稚,其程度随DES暴露剂量增加而加重。PND64时,C、Da、Db、Dc和Dd组单侧睾丸重量分别为(1.60±0.06)、(1.62±0.11)、(1.58±0.08)、(1.47±0.10)g和(0.99±0.37)g,其中Dc和Dd组较C组显著减轻(P<0.05或P<0.01);Dc和Dd组睾丸组织形态学改变与PND50时类似,但总体较PND50有所改善。PND130时,各实验组与对照组比较,单侧睾丸重量差异无统计学意义(P>0.05),睾丸组织形态学改变难以鉴别出明显差异;C、Da、Db、Dc和Dd组大鼠附睾尾精子密度分别为(73.00±16.90)、(68.00±19.67)、(68.67±12.15)、(35.17±15.64)×106/ml和(19.13±5.17)×106/ml,其中Dc和Dd组精子密度较C组明显降低(P<0.01);与C组比较,Dd组精子活动率下降(P<0.01),Db、Dc和Dd组a级精子比例降低(P<0.05或P<0.01),Dd组b级精子比例降低(P<0.01)。结论:青春期前小剂量DES[0.01μg/(kg.d)×14d]暴露对SD大鼠睾丸发育及功能无明显影响,较大剂量DES[1.0～10.0μg/(kg.d)×14d]暴露对大鼠睾丸发育及功能有明显的近期(PND50和PND64)和较远期(PND130)毒性作用,该毒性作用随DES的暴露剂量增加而加重,随鼠龄增长而逐渐减退,其机制可能与间质细胞和支持细胞的发育及功能受损相关。     

PI3K/AKT抑制剂对前列腺增生的影响及机制研究

目的:探讨磷脂酰肌醇3激酶/蛋白激酶B(PI3K/PKB或PI3K/AKT)信号通路抑制剂对前列腺增生的影响及机制。方法:选用鼠龄12周的雄性SD大鼠48只,随机分为4组:假手术对照组;BPH模型组;LY294002 50 mg组和LY294002 100 mg组,每组12只。大鼠去势后肌注丙酸睾酮10 mg/(kg.d)连续30 d建模,LY294002 50 mg组和100 mg组同时肌注LY294002 50 mg/kg和100 mg/kg,隔日1次。给药30 d后,切除各组大鼠前列腺组织,称取前列腺重量,切片观察前列腺组织细胞结构变化。免疫组化法检测K i-67、凋亡相关蛋白Bc l-2与Bax的表达情况;核酸末端原位标记法(TUNEL)检测细胞凋亡情况。结果:各组大鼠前列腺湿重(mg)和前列腺指数:假手术对照组:551±10.8,1.61±0.05;模型组:687±13.8,2.15±0.12;LY294002 50 mg组:623±23.5,1.95±0.11,与模型组相比,差异有显著性(P<0.05);LY294002 100 mg组:561±12.6,1.71±0.18,与模型组相比,差异具有极显著性(P<0.01)。凋亡相关蛋白Bax与Bc l-2的表达:假手术对照组:16.7%,16.7%;模型组:16.7%,58.3%;LY294002 50 mg组:33.3%,33.3%,与模型组相比,差异有显著性(P<0.05);LY294002 100 mg组:50.0%,25.0%,与模型组相比,差异极有显著性(P<0.01)。增殖和凋亡指数(%):假手术对照组:上皮组织14.2±6.4,6.5±1.8,间质组织7.6±2.6,2.5±0.3;模型组:上皮组织50.9±12.8,2.7±1.4,间质组织16.5±5.7,1.3±0.8;LY294002 50 mg组:上皮组织32.0±13.8,6.2±2.5,间质组织12.1±3.8,1.6±1.1;与模型组相比,差异有显著性(P<0.05);LY294002 100 mg组:上皮组织17.8±14.7,7.4±3.6,间质组织9.5±3.4,2.2±1.3;与模型组相比,差异有显著性(P<0.05)或极显著性(P<0.01)。结论:前列腺增生动物模型前列腺细胞增殖增加和凋亡的相对减少参与了BPH的发生发展过程。PI3K/AKT介导的信号通路在前列腺增生的发生发展过程中起重要作用,阻断PI3K/AKT信号通路具有抑制前列腺增生的作用。     

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.     

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.     

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.     

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.     

Immunomodulation in Transplantation with Photopheresis

Abstract: Photopheresis is a technique in which peripheral blood mononuclear cells, in the presence of a photoacti-vatable compound, are exposed extracorporeally to ultraviolet A light and reinfused, inducing a host autoregula-tory immune response. Experimental work and ongoing clinical studies are helping to define the role of this novel, safe, and non-toxic immunomodulating technology in the field of transplantation.