五味子乙素调节AMPK/mTOR信号通路对高糖诱导骨髓间充质干细胞功能障碍和自噬的影响

目的 探究五味子乙素（SchB）对高糖（HG）条件下骨髓间充质干细胞（BMSCs）增殖和成骨分化的影响及机制。方法 分离大鼠BMSCs并筛选SchB的实验浓度。将BMSCs分为正常（NC）组、高糖（HG）组、HG+10 μmol/L SchB组、HG+20 μmol/L SchB组、HG+40 μmol/L SchB组、HG+40 μmol/L SchB+AMPK抑制剂Compound C（CC）组。CCK-8法检测细胞活力,碱性磷酸酶（ALP）活性测定和茜素红染色评估BMSCs成骨分化能力;qRT-PCR检测BMSCs中成骨分化相关基因（RUNX2、COl1a1、OCN、BMP2）表达;透射电子显微镜（TEM）观察自噬体数量;Western blot检测自噬（LC3A/B、Beclin-1、P62）,以及AMPK/mTOR信号通路相关蛋白表达。结果 HG环境能抑制BMSCs增殖和成骨分化,并降低自噬体数量、Beclin-1蛋白水平和LC3II/LC3I、p-AMPK/AMPK比值,升高P62蛋白水平和p-mTOR/mTOR比值（均P＜0.05）,抑制AMPK/mTOR通路介导的自噬。SchB可促进HG条件下BMSCs的增殖和成骨分化,并升高自噬体数量、Beclin-1蛋白水平和LC3II/LC3I、p-AMPK/AMPK比值,降低P62蛋白水平和p-mTOR/mTOR比值（均P＜0.05）,激活AMPK/mTOR通路介导的自噬。Compound C可阻断HG条件下SchB对BMSCs增殖、成骨分化和自噬的促进作用。结论 SchB可能通过激活AMPK/mTOR介导的自噬促进HG条件下BMSCs的增殖和成骨分化。     

2型糖尿病性骨质疏松大鼠ADSCs成骨能力的研究

目的探讨2型糖尿病性骨质疏松(DOP)大鼠自身脂肪干细胞(ADSCs)的体外成骨分化能力。方法将60只SD大鼠分为对照组、骨质疏松组(OP组)及2型糖尿病性骨质疏松组(DOP组),每组20只。DOP组大鼠喂食高脂高糖饲料后于左下腹部经腹腔注射STZ先建立2型糖尿病大鼠模型,再行卵巢切除术建立2型糖尿病性骨质疏松模型;OP组大鼠行卵巢切除术建立骨质疏松大鼠模型,对照组仅切除卵巢周围脂肪。对照组随机选取10只大鼠,DOP组及OP组从建模成功的大鼠中各随机选取10只作研究。从各研究大鼠腹股沟区脂肪组织中分离脂肪干细胞,培养并传代,取第3代细胞作成骨结节染色及定量分析,PCR检测成骨基因RUNX2、OCN、OPN、ALP mRNA的表达。结果造模后DOP组大鼠BMD明显低于对照组及OP组(P0.05);三组大鼠ADSCs细胞形态学及增殖情况无显著性差异;显微镜下观察见DOP组与OP组ADSCs的钙化结节量较对照组少,DOP组钙化结节最少,并且缺少大片状结节,染色较浅;成骨定量分析结果可得DOP组ADSCs的OD值低于对照组及OP组,差异有统计学意义(P0.05);RT-PCR检测成骨基因的表达,DOP组与OP组RUNX2、OCN、OPN、ALP mRNA的表达量均低于对照组(P均0.05),DOP组与OP组相比较,DOP组RUNX2与ALPmRNA的表达量明显低于OP组(P0.05),而OCN与OPNmRNA的表达量两组无明显差异(P0.05)。结论 DOP大鼠ADSCs成骨分化能力较弱,弱于单纯骨质疏松大鼠,原因可能与高血糖状态下其ADSCs中ALP和RUNX2的表达减少有关。     

白茅苷对去卵巢大鼠骨髓间充质干细胞功能和骨量的影响

目的观察白茅苷治疗去卵巢大鼠骨髓间充质干细胞功能和骨量的影响并初步探索可能机制。方法通过双侧去卵巢建立骨质疏松大鼠模型;随后随机分为假手术组(Sham)、去卵巢组(OVX)以及白茅苷组(BMG),每组10只;其中BMG组去卵巢大鼠每天给予白茅苷(20 mg/kg)灌胃治疗;待12周治疗结束后分离培养各组大鼠骨髓间充质干细胞(BMSCs),使用碱性磷酸酶(ALP)和茜素红(ARS)染色并使用蛋白质印迹检测BMP-2、Runx2、OPN、OCN、ALP和Col1蛋白表达;进一步使用Micro-CT和骨生物力学检测观察治疗效果。结果 OVX组大鼠BMSCs向成骨细胞分化后ALP和ARS染色阳性面积以及BMP-2、Runx2、OPN、OCN、ALP和Col1表达较Sham组明显降低(P0.05);而经过BMG治疗,BMG组大鼠BMSCs向成骨细胞分化后ALP和ARS染色阳性面积以及BMP-2、Runx2、OPN、OCN、ALP和Col1表达较OVX组明显增加(P0.05)。OVX组股骨最大载荷和弹性模量、BMD、BV/TV、Tb.N和Tb.Th较Sham组明显降低,而Tb.Sp则明显升高(P0.05)。BMG组左侧股骨最大载荷和弹性模量、BMD、BV/TV、Tb.N和Tb.Th均明显高于OVX组(P0.05),而Tb.Sp明显低于OVX组(P0.05)。结论白茅苷通过促进BMSCs诱导成骨分化来减少去卵巢大鼠骨骨密度、骨量和骨强度下降。     

IGF-1介导MAPKs通路在C3H10T1/2细胞成骨分化中的作用

目的 探究胰岛素样生长因子1(IGF-1)介导丝裂原活化蛋白激酶(MAPKs)信号通路在C3H10T1/2细胞成骨分化中的调控作用及机制。方法 不同浓度IGF-1(0、5、10、20 ng/mL)培养C3H10T1/2细胞,碱性磷酸酶(ALP)与茜素红(ARS)染色检测ALP活性、钙盐沉积情况,qRT-PCR法检测成骨特性因子核心结合因子α-1(RUNX2)、成骨分化特异性因子骨桥蛋白(OPN)、骨钙蛋白(OCN)mRNA表达水平,Western Blot法检测MAPK通路蛋白磷酸化表达水平。对数期细胞分为空白组、IGF-1组、ERK通路抑制剂(PD98059)组、PD+IGF-1组、p38通路抑制剂(SB202192)组、SB+IGF-1组,qRT-PCR法检测成骨特性因子RUNX2、成骨分化特异性因子骨桥蛋白(OPN)、骨钙蛋白(OCN)mRNA表达水平。结果 不同浓度IGF-1组ALP显色加深,ALP活性升高,钙盐结节形成增多,RUNX2、OPN、OCN mRNA表达水平升高,磷酸化ERK、p38、JNK蛋白表达增加,具有剂量效应(P<0.05)。与空白组比较,PD组、SB...     

miR-187-5p 对骨髓间充质干细胞成骨分化能力的调控作用

目的利用小鼠骨髓间充质干细胞(BMSCs)的成骨分化模型,探讨miR-187-5p在成骨分化中的表达趋势及调控作用。方法通过切除雌性小鼠双侧卵巢构建小鼠骨质疏松模型;应用qRT-PCR技术检测组织和细胞中miR-187-5p的表达;应用基因转染技术观察过表达或敲减miR-187-5p对BMSCs向成骨分化的影响;应用茜素红和碱性磷酸酶染色检测BMSCs中矿化结节的数量和矿化区域的染色面积。结果 qRT-PCR结果显示miR-187-5p在骨质疏松模型小鼠的骨组织及BMSCs中均表达下降。过表达miR-187-5p可提高ALP、Collagen-1、Runx2、BMP4、OCN和OPN等成骨分化相关基因mRNA的表达,促进BMSCs向成骨分化;而敲减miR-187-5p降低ALP等成骨分化相关基因mRNA的表达,抑制BMSCs向成骨分化。在体实验同样证实,过表达miR-187-5p可以显著促进骨质疏松小鼠BMSCs向成骨分化,改善小鼠的骨质疏松表型。结论过表达miR-187-5p促进BMSCs向成骨分化,敲减miR-187-5p抑制BMSCs向成骨分化。     

环指蛋白11调控Akt信号通路促进BMSCs成骨分化的机制研究北大核心CSCD

目的研究BMSCs成骨分化过程中环指蛋白11(ring finger protein 11,RNF11)对Akt信号通路的调节作用,为进一步阐明BMSCs成骨分化机制和用于临床治疗提供思路。方法从健康人体新鲜骨髓中分离培养BMSCs并传代,取第4代细胞经流式细胞术,成骨、成软骨和成脂诱导培养鉴定后用于实验。BMSCs成骨诱导分化培养0~14 d,通过茜素红染色和ALP染色检测其成骨分化程度,并用Western blot法检测RNF11蛋白表达。取第4代BMSCs,分为空白对照组(A组)、空载慢病毒(Lv-NC)组(B组)和敲低RNF11(Lv-ShRNF11)组(C组),成骨诱导分化培养0~14 d,采用Western blot检测RNF11蛋白表达,茜素红染色和ALP染色检测其成骨分化程度,14 d实时荧光定量PCR(real-time fluorescence quantitative PCR,qRT-PCR)检测BMSCs成骨标志物Runx2、骨钙素(osteocalcin,OCN)及骨桥蛋白(osteopontin,OPN)的mRNA相对表达量;采用Western blot检测Akt、Smad1/5/8及β-catenin信号通路蛋白相对表达量,以磷酸化前后比值表示。为研究RNF11对Akt信号通路的影响机制,取第4代BMSCs分为Lv-NC转染组(A1组)、Lv-ShRNF11转染组(B1组)和添加Akt信号通路激活剂SC79的Lv-ShRNF11转染组(C1组),14 d时采用Western blot检测RNF11和Akt信号通路蛋白相对表达量,茜素红染色、ALP染色及qRT-PCR检测成骨相关指标。结果流式细胞术及成骨、成软骨和成脂诱导培养鉴定显示分离培养细胞为BMSCs。RNF11蛋白相对表达量随成骨分化时间延长而逐渐增加(P<0.05);下调RNF11后,茜素红和ALP染色示C组相较于A、B组BMSCs成骨分化程度降低,qRT-PCR检测示Runx2、OCN、OPN mRNA相对表达量减少(P<0.05)。随成骨分化时间延长,RNF11与Akt信号通路蛋白相对表达量均上升(P<0.05)。下调RNF11后,C组相较于A、B组,其Akt信号通路蛋白相对表达量显著降低(P<0.05),而对Smad1/5/8以及β-catenin信号通路蛋白相对表达量无明显影响(P>0.05)。B1、C1组相较于A1组,其RNF11蛋白相对表达量减少(P<0.05),B1组相较于A1、C1组,其Akt信号通路蛋白相对表达量降低(P<0.05);茜素红与ALP染色示C1组BMSCs成骨分化程度稍低于A1组(P>0.05),而明显高于B1组(P<0.05);qRT-PCR检测示C1组Runx2、OCN、OPN mRNA相对表达量稍低于A1组(P>0.05),而明显高于B1组(P<0.05)。结论RNF11通过正向调控Akt信号通路激活水平促进BMSCs向成骨细胞分化。RNF11可作为提高BMSCs修复骨缺损疗效以及治疗骨代谢病的潜在靶点。     

LncRNA DANCR靶向调控对绝经后骨质疏松BMSCs成骨分化的作用

目的 研究长链非编码RNA（lncRNA）分化非蛋白编码 RNA（DANCR）靶向微小RNA（miR）-19a-3p对绝经后骨质疏松（PMOP）骨髓间充质干细胞（BMSCs）成骨分化的调控作用。方法 选择健康女性志愿者4例和PMOP患者4例，分离培养BMSCs；PMOP患者BMSCs进行分组，转染阴性对照（NC）siRNA、lncRNA DANCR siRNA、miR-NC抑制物、miR-19a-3p抑制物。检测lncRNA DANCR、miR-19a-3p、PTEN的表达水平，成骨诱导分化后检测茜素红染色的OD405水平、碱性磷酸酶（ALP）活力、骨钙素（OCN）及骨桥蛋白（OPN）的mRNA表达水平。结果 PMOP患者BMSCs中lncRNA DANCR、PTEN的表达水平高于健康女性，miR-19a-3p的表达水平及成骨诱导后的OD405水平、ALP活力、OCN及OPN的表达水平均低于健康女性。在PMOP患者BMSCs中，si-DANCR组的lncRNA DANCR、PTEN的表达水平低于si-NC组，成骨诱导后的OD405水平、ALP活力及miR-19a-3p、OCN、OPN的表达水平高于si-NC组；si-DANCR+miR-19a-3p抑制物组成骨诱导后的OD405水平、ALP活力及miR-19a-3p、OCN、OPN的表达水平低于si-DANCR+miR-NC抑制物组，PTEN的表达水平高于si-DANCR+miR-NC抑制物组。结论 LncRNA DANCR靶向miR-19a-3p调控PMOP患者BMSCs的成骨分化。     

绝经后骨质疏松症病人骨髓间充质干细胞STIM1与成骨分化关键因子的表达变化

目的探讨绝经后骨质疏松症病人骨髓间充质干细胞(BMSCs)基质交感分子1(STIM1)与成骨分化关键因子碱性磷酸酶(ALP)、骨桥蛋白(OCN)、骨钙素(OPN)的表达变化情况。方法通过临床取材获得并培养绝经后骨质疏松症病人BMSCs,加入成骨诱导液孵育14天,采用RT-PCR检测ALP、OPN、OCN的转录水平及ALP的活性,并检测STIM1的表达情况。采用ALP染色法检测ALP活性;采用Alizarin Red染色法检测钙结节形成数量;采用Fluo荧光法检测钙离子内流变化。结果通过无菌培养,获得高纯度绝经后骨质疏松症(观察组)病人的BMSCs,经成骨诱导14天后,观察组病人BMSCs中成骨分化关键因子ALP、OPN、OCN的转录水平以及ALP的活性均低于对照组(P0.05),同时STIM1 mRNA的表达水平也相应下降,钙离子内流较对照组减少(P0.05)。另外,观察组病人BMSCs钙结节形成数量少于对照组。结论绝经后骨质疏松的发病机制可能与由STIM1参与调控的钙释放激活钙离子通道开放情况密切相关,可作为绝经后骨质疏松病人预防和治疗的潜在靶点。     

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 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.     

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.