甲酰基肽受体1对脊髓损伤后小胶质细胞诱导的炎性反应的影响

目的 探讨甲酰基肽受体1（Fpr1）是否参与脊髓损伤（SCI）后小胶质细胞诱导的炎性反应，为SCI后减轻神经炎性反应提供理论依据。方法 将30只成年C57BL/6雄性小鼠按照随机数字表法分为假手术组（Sham组）和不同时间点SCI组（术后1、3、5、7 d），每组6只。采用蛋白质印迹检测小鼠SCI后不同时间点损伤周围脊髓组织Fpr1蛋白的表达变化，采用免疫荧光实验检测Fpr1在小胶质细胞中的定位。选择Fpr1蛋白表达水平最高时间点制作小鼠模型进行进一步实验，将小鼠随机分为SCI组和Fpr1抑制剂（HCH6-1）干预组（HCH6-1干预组），每组6只，并与Sham组比较，应用免疫荧光实验评估各组小胶质细胞的活化程度，通过蛋白质印迹检测各组炎性因子［白细胞介素（IL）-1β、IL-18和肿瘤坏死因子-α（TNF-α）］以及炎性小体（NLRP3、ASC和Caspase-1）蛋白的表达情况。结果 与Sham组相比，Fpr1在SCI后第1天开始表达增多，第3天最高，第5天下降，第7天下降至与Sham组水平相当。免疫荧光染色结果提示，Fpr1主要表达在小胶质细胞。与SCI组相比，HCH6-1干预组小胶质细胞的活化程度显著减轻，炎性因子（IL-1β、IL-18和TNF-α）和炎性小体（NLRP3、ASC和Caspase-1）的表达显著减少。结论 Fpr1能够介导SCI后小胶质细胞诱导的炎性反应，抑制Fpr1有望成为干预SCI后继发性损伤的新治疗策略。     

过载静压下益肾活血通络含药血清对人椎间盘髓核细胞凋亡的影响

目的：探讨在过载静压应力下益肾活血通络方含药血清对人椎间盘髓核细胞凋亡的影响及其相关机制。方法：将人椎间盘髓核细胞分为3组,空白组无任何干预,模型组和中药血清干预组在体外3 MPa压应力干预下作用2、4、6 h后,观察椎间盘髓核细胞的形态、生长状况、超微结构的变化及差异;检测椎间盘髓核细胞的凋亡率及髓核细胞内核因子κB p65（nuclear factor kappa-B p65,NF-κB p65）,Y染色体中性别决定区相关的高迁移率组框9（SRY-related high mobility group-box 9,SOX9）,C/EBP同源蛋白（C/EBP-homologous protein,CHOP）,基质金属蛋白酶-13（matrix metalloprotein-13,MMP-13）蛋白和相对应基因表达情况。结果：同一作用时间下模型组髓核细胞与空白组比较：体积缩小、胞浆减少、生长状况更差;中药血清干预组髓核细胞较模型组体积稍大,形态保存更完整,胞浆更丰富,生长状况更好。同一作用时间下空白组髓核细胞超微结构完整,主级突起、次级突起结构未见断裂,模型组与中药血清干预组超微结构破坏,主级突起、次级突起可见不同程度断裂,两组超微结构未见明显差异。相同作用时间下模型组髓核细胞凋亡率高于空白组,而中药血清干预组髓核细胞凋亡率低于模型组（P<0.05）;随作用时间增加,空白组、中药血清干预组椎间盘髓核细胞凋亡率未见明显差异,模型组椎间盘髓核细胞凋亡率增加。相同作用时间下,中药血清干预组较模型组NF-κB p65、CHOP、MMP-13表达减少,SOX9表达增多（P<0.05）;随作用时间的增加,空白组、模型组髓核细胞的NF-κB p65、CHOP、MMP-13表达增多,SOX9表达减少,且模型组表达程度较空白组大（P<0.05）;通过基因表达总体来看,在相同作用时间下,中药血清干预组髓核细胞基因NF-κB p65、CHOP、MMP-13相对定量较模型组均减少,而SOX9相对定量增多（P<0.05）;空白组髓核细胞基因NF-κB p65、CHOP、MMP-13相对定量比模型组减少,而SOX9相对定量增多（P<0.05）;随作用时间的增加,空白组、模型组髓核细胞的NF-κB p65、CHOP、MMP-13相对定量增多,SOX9相对定量减少（P<0.05）。结论：益肾活血通络方能减少过载静压下髓核细胞的凋亡,具有延缓髓核细胞退变的作用,其机制可能通过抑制髓核细胞NF-κB p65信号通路,使CHOP、MMP-13表达减少,SOX9表达增加有关。     

NLRP3炎性小体在激素性股骨头坏死骨代谢及其稳态中的作用

大量的糖皮质激素使用导致股骨头中骨代谢及稳态失衡是激素性股骨头坏死的重要机制之一。细胞焦亡关键因子NLRP3炎性小体在SANFH机制中发挥着重要作用，明确NLRP3炎性小体的结构，激活途径和调控机制，以及NLRP3炎性小体和下游炎性因子IL-1β、IL-18对激素性股骨头坏死中成骨细胞、破骨细胞以及骨髓间充质干细胞的作用机制，将为激素性股骨头坏死的防治提供新的思路与靶点。该文对NLRP3炎性小体在骨代谢及稳态中的相关作用机制进行综述，系统阐述NLRP3炎性小体与SANFH成骨和破骨分化中的具体作用机制，以期为临床治疗和基础研究提供一定的借鉴。     

线粒体自噬对脂多糖诱导髓核细胞NOD样受体热蛋白结构域相关蛋白3炎症小体活化的实验研究

目的探讨线粒体自噬对脂多糖(LPS)诱导的髓核(NP)细胞NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎症小体活化的影响。方法以大鼠椎间盘NP细胞为研究对象, 首先以LPS(200 μg/ml)分别干预髓核细胞0、24、48 h, 通过蛋白质印迹法(Western blot)检测LPS对NLRP3炎症小体活化和线粒体自噬的影响;通过免疫荧光观察LPS对线粒体自噬水平的影响;组间比较采用单因素方差分析。进一步利用线粒体自噬抑制剂Mdivi-1阻断线粒体自噬, 实验分组为对照组(con)、LPS(24 h)+Mdivi-1、LPS(24 h)。通过Western blot检测Mdivi-1对LPS诱导的NLRP3炎症小体活化的影响;通过免疫荧光评估各实验组Mito Tracker Red探针标记的线粒体与LC3B及NLRP3的细胞内共定位;通过免疫荧光评估各实验组Mito Tracker Red探针标记的线粒体与LC3B的细胞内共定位;通过免疫荧光检测分析Mdivi-1对LPS诱导的NP细胞线粒体膜电位(ΔΨm)及线粒体ROS的影响;组间比较采用t检验。结果与对照组比较, 随着LPS干...     

含pyrin结构域NOD样受体家族3炎性小体的翻译后修饰及其在脓毒症发生发展中的作用

翻译后修饰(post-translational modification, PTM)主要包括磷酸化、泛素化、烷基化、S-亚硝基化和ADP-核糖基化等,能够通过多分子多位点调控含pyrin结构域NOD样受体家族3(NOD-like receptors family pyrin domain containing 3, NLRP3)炎性小体。NLRP3炎性小体激活将造成炎症级联反应不断扩大。而这种炎症反应紊乱是推动脓毒症进展的重要因素。文章详细阐述了NLRP3炎性小体的PTM,并介绍了NLRP3的PTM在脓毒症中的作用,以期干预NLRP3炎性小体的活化,进而调控炎症,为未来脓毒症治疗提供新思路。     

炎性小体的研究进展

炎性小体是由多种蛋白质组成的复合体,分子量约700 kD,此概念由Tschopp研究小组于2002年首次提出[1].炎性小体能够调节胱冬肽酶-1(caspase-1)的活化进而在天然免疫防御的过程中促进细胞因子前体pro-IL-1β和pro-IL-18的切割成熟[2];还能调节caspase-1依赖的形式编程性细胞死亡(pyroptosis)[3],诱导细胞在炎性和应激的病理条件下死亡.目前已发现的炎性小体主要有4种,即NLRP1、NLRP3、IPAF和AIM2炎性小体.已发现的炎性小体一般均含有凋亡相关微粒蛋白(apoptosis-associated speck-like protein containing CARD,ASC)、caspase蛋白酶及一种NOD样受体(NOD-like receptor,NLR)家族蛋白(如NLRP1)或HIN200家族蛋白(如AIM2).炎性小体活性异常与人类的多种遗传疾病或后天疾病发生相关,如遗传性周期发热综合征等[4].     

高渗应激下ERK信号转导通路在兔髓核细胞凋亡中的作用

[目的]观察高渗透压对体外培养的兔髓核细胞凋亡的影响及细胞外信号调节激酶(ERK1/2)信号转导通路在此过程中的作用.[方法]用不同的渗透压梯度以及ERK1/2特异性抑制剂PD 98 059(50 μmol/L)分不同作用时间处理髓核细胞;流式细胞仪检测髓核细胞在不同处理组的凋亡情况,蛋白质免疫印迹技术检测各组ERK1/2和p- ERK1/2蛋白的表达情况;免疫荧光标记技术检测p- ERK1/2蛋白在髓核细胞内的分布情况.[结果]高渗透压(600 mOsm)培养基中兔髓核细胞凋亡显著增加,与对照组相比差异有统计学意义(P=0.013),并呈时间依赖性;PD98059预处理组与相应时间段同渗透压组相比,细胞凋亡进一步显著地增加(P=0.035);400 mOsm组及其抑制组在各时间段细胞凋亡均不明显;600 mOsm高渗透压显著激活p- ERK1/2的表达,并且在3h组表达水平最高,与对照组比较差异显著(P--0.027),而PD98059几乎阻断p- ERK1/2的表达;免疫荧光标记检测到p- ERK1/2在600 mOsm高渗组的细胞胞浆和胞核中均有分布.[结论]高渗透压(600 mOsm)应激下兔髓核细胞凋亡显著增加,而且激活的ERK1/2信号转导通路具有抵抗髓核细胞凋亡的作用;并且髓核细胞能够适应轻度增加的渗透压(400mOsm)环境.     

β肾上腺素受体激活诱导人系膜细胞凋亡

目的 探讨β肾上腺素受体(β-AR)激活对人肾小球系膜细胞(HMC)凋亡的影响及其机制.方法 HMC被分为空白对照(Ctrl)组;β-AR激活(NE/Pra)组;β-AR抑制(Prop)组;抗氧化剂(VC和NAC)组.采用反转录PCR法检测系膜细胞β肾上腺素受体的表达;激光共聚焦术测定细胞内钙信号变化;Tunel法检测细胞凋亡;Western印迹法检测细胞内半胱天冬酶3 (Caspase-3)的表达.结果 反转录PCR结果显示,人系膜细胞有β1-AR和β2-ARmRNA表达;激光共聚焦结果显示,β1-AR和β2-AR激动剂均能诱导系膜细胞内钙信号变化(P＜ 0.05);β-AR激活组诱导人系膜细胞产生活性氧类(ROS)增加,β-AR激动剂作用后ROS从0.5 h开始增多,4h达到高峰,之后减弱,但在12h时,细胞内ROS仍然超过对照组(P＜0.01).并且随着β-AR激动剂浓度增加,ROS生成增加.与对照组相比,β-AR激活组诱导人系膜细胞凋亡率增加,并随β-AR激动剂浓度增加和作用时间延长,凋亡细胞数随之增加(均P＜ 0.01).抗氧化剂维生素C和NAC可减轻由β-AR激活诱导的细胞凋亡(P＜0.01),β-AR阻断剂普萘洛尔可减轻细胞内ROS产生和β-AR激活诱导的细胞凋亡.与对照组相比,β-AR激活可诱导系膜细胞Caspase-3表达上调(均P＜ 0.01).结论 β-AR激活可诱导人系膜细胞凋亡,其机制可能是与β-AR激活增加细胞内氧化应激水平有关.     

低氧环境对椎间盘自发性吸收的影响及其作用机制

目的探讨低氧环境对椎间盘自发性吸收的影响及其作用机制。方法取SPF级成年日本大耳兔9只,雌雄不限,平均体质量2 kg。将兔处死后取脊柱髓核组织,经消化、分离、培养后获得传代髓核细胞,将生长良好的髓核细胞制成细胞悬液。根据不同时效的低氧环境将细胞分为5组对照组(常氧浓度下培养6 h)、低氧6 h组(2%O2浓度下培养6 h)、低氧12 h组(2%O2浓度下培养12 h)、低氧24 h组(2%O2浓度下培养24 h)和低氧48 h组(2%O2浓度下培养48 h)。采用实时聚合酶链反应法检测缺氧诱导因子(HIF)-1α、3型酸敏感离子通道(ASIC3)及水通道蛋白3(AQP3)mRNA表达水平,采用流式细胞仪检测各组髓核细胞凋亡情况。采用SPSS 24.0软件对数据进行分析。结果与对照组比较,低氧各组细胞凋亡率均明显升高,差异均有统计学意义(均P<0.01);与低氧12、24和48 h组比较,低氧6 h组细胞凋亡率最高,差异均有统计学意义(均P<0.01)。与对照组比较,低氧各组细胞HIF-1α和ASIC3 mRNA表达水平均明显上升,AQP3 mRNA表达水平均明显下降,差异均有统计学意义(均P<0.01);与低氧12、24和48 h组比较,低氧6 h组HIF-1α和ASIC3 mRNA表达水平最高,差异均有统计学意义(均P<0.01)。结论短时间低氧环境可以促进髓核细胞凋亡,从而加速椎间盘突出组织自发性吸收进程,其机制可能与HIF-1α和ASIC3的表达增加及AQP3的表达下降有关。     

热休克蛋白72抑制ATP耗竭时细胞色素C释放所诱导的肾小管上皮细胞凋亡

目的 研究热休克蛋白(HSP)72对ATP耗竭时细胞色素C释放所导致的肾小管上皮细胞凋亡的保护作用及其分子机制。方法 应用代谢抑制剂暂时性阻断细胞内ATP的生成,引起细胞凋亡。应用热处理细胞或编码HSP72 RNA的腺病毒感染细胞,诱导HSP72的表达。以Western印迹检测释放于胞浆内的细胞色素C。荧光肽法测定半胱氨酸天冬氨酸蛋白酶(caspase)3活性。Hoechst33342染色观察细胞凋亡的发生情况。结果 肾小管上皮细胞内ATP耗竭时,释放至胞浆内的细胞色素C的含量增多,caspase 3活性增强;细胞内ATP再恢复时,细胞色素C的释放和caspase 3活性进一步增加,细胞体积缩小,核浓染、固缩,形成凋亡小体。预先热处理后,各组细胞色素C的释放明显减少,caspase 3活性显著抑制(P<0.05,n=3)。高表达HSP72时,各时间点caspase 3活性的抑制程度与热处理组相似,细胞体积缩小,核浓染、固缩,凋亡小体的形成明显减少。结论 HSP72可抑制ATP耗竭时细胞色素C所导致的肾小管上皮细胞凋亡,其机制是抑制凋亡通路中细胞色素C的释放和caspase 3的激活。     

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.