γ干扰素刺激肝细胞癌细胞表达共刺激分子和主要组织相容性复合物的研究

目的 研究共刺激分子（CD80和CD86）和主要组织相容性复合物（MHC）在肝细胞癌（HCC）细胞中的表达，探讨γ干扰素（γ－INF）治疗HCC中的免疫作用机理。方法 应用流式细胞仪测定CD80、CD86和MHCⅡ类分子HLA－DR，以及应用微量细胞毒方法测定MHCⅠ类分子在γ－INF刺激前后8种HCC细胞中的表达。结果 所有未受刺激的HCC细胞的CD80、CD86和HLA－DR表达率均不超过3.58%，只有3种细胞中测到MHCⅠ类分子的表达；γ－INF以10^6U／L的浓度刺激48h后，所有8种HCC细胞HLA－DR表达率均升高，其中7种升高至18％以上，5种升高至70％以上，荧光强度增强10－50倍；刺激后，在8种细胞中均可测到MHCⅠ类分子表达；刺激后，所有8种HCC细胞CD86表达率均升高，7种升高至12.35%-17.10%，5种HCC细胞CD80表达率升高至5％－10％。结论 γ－INF刺激可使多数被研究的HCC细胞获得一定的抗原呈递能力，同时可使所有被研究的HCC细胞获得被细胞毒T淋巴细胞识别和杀伤的条件。     

干扰素-γ对大鼠胚胎神经干细胞发育的影响

目的探讨感染后细胞因子干扰素（IFN）-γ对胎鼠神经系统发育的影响。方法利用不同浓度IFN-γ（0、20、200、2,000U／ml）对大鼠体外培养的胚胎16d的神经干细胞进行刺激,观察神经干细胞生长状态、主要组织相容性复合体（MHC）表达和分化格局的变化。结果高浓度的IFN-γ（2,000U／ml）对神经干细胞具有毒性作用。中等浓度的IFN-γ（200u／ml）能够显著上调神经干细胞MHc—Ⅰ类和Ⅱ类分子的表达。同时,中等浓度的IFN-γ能够促进神经干细胞的分化,使得神经干细胞向神经元和少突胶质细胞分化增加,而向星形胶质细胞的分化降低。结论大剂量IFN-γ可改变神经干细胞的生长和分化状态,IFN-γ除了对胎儿神经系统具有直接毒性外,还可能通过影响MHC的表达引起母体对胎儿的排斥,也许对新生儿智力发育造成不利影响。     

大鼠小肠系膜淋巴组织抗原刺激同种异体混合淋巴细胞增殖反应研究

目的探讨大鼠小肠系膜淋巴组织通过树突状细胞（DC）和外周血单核细胞（PBMC）作用后刺激混合淋巴细胞增殖强度和与DC作用后MHC类分子表达变化。方法分离培养SD大鼠DC、PBMC、混合淋巴细胞,获取Winstar大鼠肠系膜淋巴结组织悬液。CCK-8检测法测定负载肠系膜淋巴组织抗原的Dc和PBMC,及负载肠系膜淋巴组织抗原和卵白蛋白（OVA）抗原的DC对混合淋巴细胞刺激增殖能力;流式细胞仪分析肠系膜淋巴组织作用于DC后,其MHC类分子表达变化。结果获得的大鼠小肠淋巴组织悬液中,淋巴细胞占91％,其余包括少量粒细胞、浆细胞、上皮细胞等;在各组中负载肠系膜淋巴组织抗原的DC对混合淋巴细胞刺激增殖能力,均强于PBMC（P〈0．05）;在DC与混合淋巴细胞比例≥1：100各组中,负载肠系膜淋巴组织抗原的DC,对混合淋巴细胞刺激增殖能力,强于负载OVA抗原的DC（P〈0．05）;肠系膜淋巴细胞组织刺激DC后,其MHC—Ⅰ和Ⅱ类分子表达高于未加入抗原组。结论小肠系膜淋巴组织具有强抗原性;DC抗原呈递作用强于单核细胞;负载肠系膜淋巴组织抗原后的DC高表达MHC-Ⅰ、Ⅱ类分子。     

树突状细胞MyD88介导热休克蛋白60的信号转导

目的观察热休克蛋白印（HSP60）刺激对树突状细胞（DC）活性的影响，探讨髓性分化因子88（MyD88）在介导HSP60信号转导中的作用。方法培养小鼠骨髓源性DC，分为对照组、HSP60组及RNA干扰组，对照组在正常条件下继续培养2d，HSP60组加入终质量浓度为10mg／L的HSP60，RNA干扰组于加入MyD88 siRNA4h后给予10mg／L HSP60刺激，均继续培养2d。流式细胞术检测DC细胞表面CD11c、CD80、CD86及MHC-Ⅱ分子的变化，ELISA法检测DC分泌肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）和白细胞介素-12（IL-12）的浓度，免疫细胞化学检测DC MyD88、核因子-κB（NF-κB）的表达，Western blot检测DC MyD88的变化，混合淋巴细胞培养检测T细胞增殖能力。结果3组CD11c阳性率差异无统计学意义（P〉0．05），分别为78．65％、82．40％及85．72％，HSP60组CD80、CD86及MHC-Ⅱ分子的阳性率分别为70．28％、76．49％及38．24％，较对照组（阳性率分别为28．42％、34．56％及16．28％）及RNA干扰组（阳性率分别为32．16％、40．47％及20．76％）显著增高（P〈0．05）；HSP60组TNF-α、IFN-γ及IL-12浓度显著高于对照组及RNA干扰组（P〈0．05）；HSP60组可见MyD88高表达及NF-κB核移位；HSP60组SI显著高于对照组及RNA干扰组（P〈0．01）。结论HSP60通过MyD88依赖的途径活化DC，MyD88是HSP60信号转导中的重要调节分子。     

转染IKK2dn的受者树突状细胞回输延长同种异体肾移植大鼠的存活时间

目的 探讨IKK2dn基因转染并负载供者抗原的受者未成熟树突状细胞(imDC)延长同种异体肾移植大鼠的存活时间及其机制.方法 获取和培养Lewis大鼠骨髓源性DC,转染IKK2dn并负载BN大鼠可溶性抗原进行体外实验,检测CD86和主要组织相容性复合物(MHC)Ⅱ的表达及DC刺激T淋巴细胞增殖的能力.肾移植受者为Lewis大鼠,用随即数字表法分DC组、空转染组、转染组、对照组,术前7d分别输注1×10~7个D、Adv-0-DC、负载BN抗原的Adv-IKK2dn-DC和等量生理盐水,供者均为BN大鼠.另设第三方供者组,术前处理同转染组,供者为Wistar大鼠.移植后检测各组受者T淋巴细胞的增殖能力及血清白细胞介素2(IL-2)和γ干扰素(IFN-γ)的表达水平,观察各组大鼠的存活时间和发生排斥反应情况.结果 DC的体外实验结果显示:与转染IKK2dn前相比,转染后DC仍能低水平表达CD86和MHC Ⅱ,负载供者抗原后CD86和MHCⅡ表达均增加,而转染IKK2dn后再负载供者抗原,CD86和MHC Ⅱ的表达未发生明显变化;DC负载供者抗原后,刺激T淋巴细胞增殖的能力明显增强(P<0.05),而转染IKK2dn并负载供者抗原后不能有效刺激T淋巴细胞增殖.肾移植术后的检测结果显示:转染组T淋巴细胞的增殖能力明显低于其他4组(P<0.05或P相似文献   

脂肪干细胞免疫学性状的初步实验观察

目的初步研究脂肪干细胞(Adiposederivedstemcells,ADSC)表面免疫分子的表达以及体外免疫调节功能,以期为组织工程提供同种异体种子细胞来源。方法体外培养人脂肪抽吸术中获取的脂肪干细胞,体外培养至第二代,流式细胞仪检测免疫分子HLA、HLA、B7-1、B7-2、CD40的表达。1×105个/孔ADSC细胞分别刺激单一异体淋巴细胞或混合双向淋巴细胞反应,观察淋巴细胞增殖情况。同时观察ADSC经IFN-γ作用后,免疫分子表达与淋巴细胞增殖的调节情况。结果ADSC表达HLA类分子,但未检测到HLA类分子阳性表达。B7-1(CD80)、B7-2(CD86)、CD28、CD40未见明显阳性表达。人IFN-γ刺激48h后,HLA类分子表达明显增高,HLAI表达未见明显增高。异体或经IFN-γ作用的ADSC均未能刺激异体淋巴细胞增殖。同样数量的ADSC可明显抑制双相混合淋巴细胞增殖,经IFN-γ作用后抑制作用未见明显减弱。结论ADSC具有一定的体外调节淋巴细胞反应的能力,有可能成为组织工程同种异体细胞来源。     

骨髓间充质干细胞诱导肝移植术后免疫耐受的研究

目的研究骨髓间充质干细胞（Bone mesenchymal stem cell，BMSC）的免疫调节特性，评价其诱导肝移植术后免疫耐受的效果。方法贴壁分离法分离培养BMSC并鉴定其免疫表型。分别检测单纯的和用200U／ml干扰素-γ（interferon-γ，INF-γ）干预过的BMSC PDL-1、CD54、CD40、CD80、CD86、MHC-Ⅰ、MHC-Ⅱ的表达，并以此为调节细胞进行单向混合淋巴细胞实验。以CFDA标识BMSC观察其在体内向肝脏归巢情况。两袖套法建立Lewis-Brown Norway（BN）大鼠原位肝移植急性排斥反应模型。实验分2组，对照组行原位肝移植术＋输注生理盐水，实验组行原位肝移植术＋输注BMSC。观察术后一般情况、肝功能、肝脏病理、微嵌合体形成情况。结果培养出的BMSC细胞纯度高。INF-γ能上调CD54、PDL-1、MHC-Ⅰ、MHC-Ⅱ的表达，CD40、CD80、CD86均为阴性表达。BMSC呈剂量依赖性抑制淋巴细胞增生，INF-γ能增强其抑制作用。BMSC在肝脏实质内有多处定居。术后所有大鼠存活均大于14天。与对照组比，实验组大鼠术后一般情况好，嵌合体形成明显，肝功能改善明显、肝脏免疫排斥轻。结论INF-γ能增强BMSC对淋巴细胞增殖的抑制作用，BMSC能诱导肝移植免疫耐受，减轻排斥反应。这为以后BMSC应用到临床提供有利证据。     

脐血间充质干细胞的培养鉴定及成骨诱导后的免疫原性研究

目的通过观察体外培养人脐血间充质干细胞(Umbilical cord blood-mesenchymal stem cells,UCB-MSCs)并作诱导成骨分化,探讨其作为组织工程的骨种子细胞的可行性。方法体外分离培养UCB-MSCs,流式细胞仪检测细胞表面抗原的表达及其变化规律;体外成骨诱导UCB-MSCs2周,采用Alizarin Red染色和钙离子半定量测定的方法评价细胞成骨活性。取P2代UCB-MSCs细胞,流式细胞仪检测加入IFN-γ前后的HLA-Ι、HLA-Ⅱ、CD40、CD80等分子的表达情况;流式细胞仪检测UCB-MSCs在成骨诱导分化前后HLA-Ι类分子、HLA-Ⅱ类分子的表达情况以观察成骨诱导分化的MSCs免疫抗原性的变化。结果第1、3、5代细胞的CD29、CD105和CD166均呈阳性表达,而造血细胞系的表面标记CD31、CD34和CD45则呈低表达,且随传代次数增加含量逐渐下降。UCB-MSCs成骨诱导2周后,Alizarin Red染色为阳性。对照组则无明显钙盐沉积。钙离子半定量的检测结果则表明,UCB-MSCs成骨诱导2周后的钙离子含量远高于未诱导组。流式细胞检测结果显示,人UCB-MSCs高表达HLA-Ι类分子,不表达HLA-Ⅱ类分子和CD40,CD80等共刺激分子;经IFN-γ刺激诱导后,HLA-Ι类分子的表达未发生改变,HLA-Ⅱ类分子呈阳性表达,而CD40和CD80的表达仍为阴性。人UCB-MSCs在成骨诱导分化前后HLA-Ι类分子均为阳性表达;而HLA-Ⅱ类分子在成骨分化前为阴性,诱导后阳性表达率增高。结论①UCB-MSCs能诱导分化为成骨细胞,有望成为较理想的组织工程骨种子细胞;②成骨分化使UCB-MSCs的免疫原性发生相应变化。     

西罗莫司与未成熟树突状细胞延长小鼠皮肤移植存活时间的协同作用

目的 研究西罗莫司（SRL）对小鼠骨髓源树突状细胞（DC）分化及成熟的影响，观察西罗莫司与未成熟树突状细胞在延长小鼠皮肤移植存活时间中的协同作用。方法 （1）在诱导C57BL／6小鼠骨髓细胞定向分化为DC时加入SRL，通过流式细胞仪检测CD11c、CD86及MHCⅡ类分子表达情况，经脂多糖（LPS）刺激后，再检测各分子表达的变化。（2）通过单向混合淋巴细胞反应（MLR）观察经SRL处理的DC刺激同种异基因小鼠T细胞增殖情况。（3）以C57BL／6小鼠为供者，BALB／c小鼠为受者建立皮肤移植模型。观察皮肤移植前7d经尾静脉注射供者未成熟DC及经胃管连续灌注SRL7d的受者移植皮片存活情况及组织学变化。结果 （1）经SRL处理的DC表面CD11c表达仅有轻度降低，但CD86和MHCⅡ类分子表达明显减少。（2）MLR显示经SRL处理的DC刺激同种异基因小鼠T细胞增殖的能力降低。（3）受者皮肤移植术前联合应用供者未成熟DC和SRL，可减轻移植皮片炎症反应并延长其存活时间。结论 SRL对DC分化的影响不明显，但可抑制DC发育成熟。受者术前应用SRL和未成熟DC可延长皮肤移植的存活时间。     

RNA干扰阻断BT／CD28共刺激通路在小鼠心脏移植中的抗排斥作用

目的探讨RNA干扰（RNAi）技术阻断B7／CD28共刺激通路对小鼠异体心脏移植排斥反应的影响及其机制。方法经体外转录合成针对CD80 mRNA和CD86 mRNA序列特异性小片段干扰RNA（siRNA），转染供者骨髓来源的树突状细胞（DC），半定量逆转录聚合酶链反应、流式细胞仪检测DC转染CD80siRNA、CD86siRNA前后CD80 mRNA和CD86 mRNA的表达水平以及细胞表面CD80及CD86的表达情况。在小鼠异位心脏移植前7d，经静脉给受者输注经siRNA干扰后的DC（干扰DC组），同时设立同种异体对照组、环孢素A（CsA）治疗组（术后皮下注射CsA 5mg／d）、同系移植对照组和未干扰DC组（移植前输注未转染DC），观察各组移植心脏的存活时间，对移植物的排斥反应进行病理分级，并测定移植物组织中白细胞介素2（IL-2）、γ干扰素（IFN-γ）及IL-10的mRNA表达水平。结果siRNA转染DC后，其CD80 mRNA及CD86 mRNA的表达受到明显抑制，CD80、CD86的阳性率分别由84％和67％下降至35％和30％。与同种异体对照组和未干扰DC组比较，干扰DC组移植心脏存活时间明显延长（P〈0．01），组织排斥反应病理分级显著降低（P〈0．01），移植心脏组织中IL-2 mRNA和IFN-γ mRNA的表达水平明显降低（P〈0．01），而IL-10 mRNA的表达水平明显升高（P〈0．01）。结论利用RNAi敲减供者骨髓来源的DC表面B7分子的表达，以阻断BT／CD28共刺激通路，具有抑制小鼠心脏移植排斥反应的作用，其机理可能是通过诱导T淋巴细胞无能并使T辅助细胞分化向Tn2型方向偏移。     

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.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

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.     

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.