雄激素受体反义寡核苷酸对前列腺癌细胞生长的抑制作用

目的　探讨雄激素受体 (AR)反义寡核苷酸 (aODN)对前列腺癌细胞AR表达和生长的抑制作用。　方法　合成 1对AR正、反义寡核苷酸 ,与LNCaP细胞共培养 ,观察LNCaP细胞的增殖情况 ,RT PCR和Westernblot方法检测ARmRNA水平和AR蛋白表达水平。　结果　含ARaODN的培养基培养处于静止期和对数生长期的LNCaP细胞增殖较对照组均明显减慢。RT PCR证实aODN组吸光度A值 (0 .5 3± 0 .18)与ODN组 (1.14± 0 .2 1)差异有显著性意义 (P <0 .0 5 ) ,提示ARaODN可导致LNCaP细胞ARmRNA显著下调。Westernblot分析显示aODN组条带的吸光度A值 (2 6 .35± 1.33)与ODN组 (33.5 1± 1.4 8)之间差异有显著性意义 (P <0 .0 5 ) ,提示ARaODN可下调LNCaP细胞AR蛋白含量。　结论　ARaODN可抑制前列腺癌细胞AR表达并抑制前列腺癌细胞增殖。     

PEG-PLGA纳米粒子介导反基因寡核苷酸体外抗前列腺癌作用研究

目的 验证包载反雄激素受体基因三螺旋形成寡核苷酸(TFO)的聚乙二醇-聚乳酸聚乙醇酸共聚物(PEG-PLGA)纳米粒子(TFO-NPs)对前列腺癌细胞的生长抑制作用.方法 采用改良自乳化溶剂挥发法制备TFO-NPs并进行体外物化表征.将TFO-NPs、脂质体包载的TFO(TFO-Lip)和裸TFO分别转染体外培养的LNCaP细胞,倒置荧光显微镜观察转染效率,MTT法检测细胞增殖活性,RT-PCR和Western blot方法检测AR基因表达.结果 TFO-NPs平均粒径128 nm,载药量为1.02%,包封率为72.28%,在体外具有缓释作用.LNCaP细胞对TFO-NPs和TFO-Lip的摄取率显著高于裸TFO.TFO-NPs和TFO-Lip对LNCaP细胞的抑制率分别为(54.5%±6.2%)和(50.6%±6.1%)显著高于裸TFO,(7.8%±0.8%)(均P＜0.05).TFO-NPs和TFO-Lip处理组LNCaP细胞的雄激素受体表达水平显著低于裸TFO处理组.TFO-NPs和TFO-Lip处理组的转染效率、细胞抑制率和雄激素受体表达水平差异均无显著性.结论 成功制备了TFO-NPs,为反基因治疗前列腺癌的研究提供了有效基因载体.     

靶向TRPV6的siRNA对前列腺癌LNCaP细胞抑制作用的体外研究

目的:运用RNA干扰(RNAi)技术阻断前列腺癌LNCaP细胞中瞬时感受器电位离子通道蛋白V亚家族6(TRPV6)基因的表达,探讨TRPV6基因沉默对LNCaP细胞增殖、细胞周期及凋亡的影响。方法:针对TR-PV6基因,构建2条小干扰RNA(siRNA)序列;在脂质体介导下转染前列腺癌LNCaP细胞,用RT-PCR测定TRPV6mRNA的表达;MTT法和流式细胞技术测定siRNA对LNCaP细胞增殖、细胞周期及凋亡的影响。结果:两条siRNA序列均能有效地阻断LNCaP细胞中TRPV6基因在mRNA水平上的表达(P<0.01),且mRNA表达随着转染时间的延长而减少,转染72h后TRPV6mRNA的表达减少至对照组的27%和23%;siRNA转染能显著抑制LNCaP细胞增殖,转染48h细胞增殖抑制率最高,分别为34.53%和29.32%,与转染24h和72h比较有统计学意义(P<0.05);转染48h后,siRNA转染组G0～G1期细胞增多,S期细胞数量明显减少,与空白对照组及阴性对照组相比有统计学差异(P<0.01);siRNA转染组细胞的凋亡率分别为14.45%和12.73%,显著高于空白对照组及阴性对照组3.78%和5.22%(P<0.05)。结论:针对TRPV6的siRNA在体外能有效地抑制LNCaP细胞TRPV6mRNA的转录,同时能够抑制前列腺癌LNCaP细胞增殖,使细胞周期出现G0/G1期阻滞,细胞凋亡率显著增加。     

反义寡核苷酸阻断雄激素受体表达对前列腺癌细胞生长活性的影响

目的　探讨反义技术阻断雄激素受体 (AR)基因表达对前列腺癌细胞生长的影响。　方法　设计、合成针对AR基因反义寡核苷酸 (ASODN) ,在脂质体介导下转染前列腺癌细胞。采用RT PCR方法检测AR基因表达 ;MTT比色法检测细胞增殖活性 ;透射电镜、TUNEL检测细胞凋亡 ;流式细胞术分析细胞周期时相。　结果　 0 .5～ 2 .0 μmol LASODN作用 12～ 36h ,癌细胞ARmRNA水平降低 10 .45 %～ 82 .10 %(P <0 .0 5 ) ,细胞增殖活性抑制 11.8%～ 5 6 .9%(P <0 .0 5 ) ,细胞周期阻滞于G2 M期 ,部分细胞呈现典型凋亡形态学改变 ,凋亡比率为 34.2 5 %(P <0 .0 1)。　结论　应用ASODN封闭AR基因表达能抑制前列腺癌细胞体外生长活性 ,有望成为前列腺癌基因治疗的有效策略。     

聚集素抗LNCaP细胞凋亡作用的研究

目的研究聚集素抗LNCaP细胞凋亡的作用及聚集素反义寡核苷酸(AS-ODN)对肿瘤坏死因子-α(TNF-α)细胞毒性作用的影响。方法培养转染全长聚集素序列的LNCaP细胞(A)为实验组,野生型LNCaP细胞(L)及转染PIRES2-EGFP空载体的LNCaP细胞(M)为对照组,以20 ng/ml TNF-α进行诱导,MTT及ELISA法检测3组细胞增殖活性与凋亡程度；转染聚集素AS-ODN后A细胞分4组,①对照组：常规培养；②AS-ODN组：转染AS-ODN,培养液不含TNF-α；③TNF-α组：未转染AS-ODN,培养液含20ng/ml TNF-α；④TNF-α+AS-ODN组：转染AS-ODN,培养液含20ng/ml TNF-α,观察4组细胞增殖活性与凋亡程度的变化。结果L、M、A3组细胞增殖活性分别为0.84±0.03、0.85±0.04、0.95±0.03,L与M间差异无统计学意义(P＞0.05),L、M与A相比增殖活性显著降低(P值均＜0.01)。3组细胞ELISA吸光度值分别为0.59±0.04、0.62±0.03、0.33±0.04,L与M间差异无统计学意义(P＞0.05),但L、M与A相比凋亡程度显著增高(P值均＜0.01)。A细胞①～④组细胞增殖活性吸光度值分别为1.30±0.03,1.25±0.03,0.99±0.03,0.80±0.03,两两比较组间差异均有统计学意义(P值均＜0.05)；4组细胞凋亡程度吸光度值分别为0.02±0.00,0.21±0.02,0.63±0.07,1.16±0.04,两两比较组间差异均有统计学意义(P值均＜0.01)。结论转染并永久表达全长序列聚集素后,TNF-α对LNCaP细胞的细胞毒性作用显著降低,转染聚集素AS-ODN显著增强TNF-α的细胞毒性作用,聚集素具有抗LNCaP细胞凋亡的作用。     

端粒酶催化亚单位基因反义寡核苷酸诱导前列腺癌细胞凋亡的研究

目的 探讨端粒酶催化亚单位(hTRT)基因反义寡核苷酸(ASODN)对前列腺癌细胞的诱导凋亡作用。方法合成针对hTRT的28mer ASODN,转染前列腺癌细胞12～36 h后,细胞计数、透射电镜、DNA Ladder、原位末端转移酶标记技术(TUNEL)检测癌细胞凋亡;逆转录-聚合酶链反应(RT-PCR)、聚合酶链反应-酶联免疫吸附试验(PCR-ELISA)技术检测hTRT基因表达和端粒酶活性。结果0.5～2.0μmol/L ASODN转染后,癌细胞体外生长抑制16.08％～53.41％(P<0.05),部分癌细胞呈现凋亡形态学改变和DNA片段化,凋亡率为9.36％～37.54％(P<0.05),hTRT表达减弱24.48％～86.73％(P<0.01),端粒酶活性降低24.74％～76.72％(P<0.01)。 结论运用ASODN阻断端粒酶hTRT基因表达,能降低端粒酶活性,显著诱导前列腺癌细胞凋亡。     

氟他胺耐受性前列腺癌细胞系LNCaP-flu的建立

目的建立氟他胺耐受前列腺癌细胞系LNCaPflu,并初步研究其细胞特性。方法在体外氟他胺作用下,连续培养LNCaP细胞,得到可在10-7mol/L氢化氟他胺中稳定生长的LNCaP亚系,LNCaPflu。使用相差显微镜,电子显微镜,流式细胞仪,四甲基偶氮唑蓝(MTT)比色法、放免法和transwell穿膜实验对细胞特性进行鉴定。结果建立氟他胺耐药细胞系LNCaPflu,与普通LNCaP细胞相比,在氟他胺作用下,此细胞株(65.0±1.7)%处于G1期,明显少于对照组的(82.7±2.3)%(P<0.05);前列腺特异性抗原分泌活力无变化,LNCaPflu为(11.25±2.23)ng/L,LNCaP为(10.15±0.86)ng/L(P>0.05);穿膜侵袭能力未受氢化氟他胺明显影响,LNCaP穿膜数为(35.21±4.52)个/高倍视野,LNCaPflu为(26.15±3.69)个/高倍视野,(P>0.05)。结论LNCaP细胞经长时间体外培养可在氟他胺中稳定生长,LNCaPflu细胞可在体外模拟前列腺癌细胞由氟他胺敏感转化为氟他胺不敏感的过程。     

苦参碱对前列腺癌细胞增殖及雄激素受体功能的抑制作用

目的:探讨苦参碱(matrine)对雄激素依赖性前列腺癌细胞株(LNCaP)的增殖及雄激素受体(androgen re-ceptor,AR)表达的抑制作用。方法:分别用0.5、1.0、1.5、2.0、3.0g/L浓度的苦参碱作用于LNCaP细胞12、24、36h后MTT法检测细胞生长活性;台盼蓝拒染法测定细胞生长曲线;24h后流式细胞仪测定细胞周期变化;24h后Western印迹法检测细胞内AR的表达。结果:苦参碱能抑制LNCaP细胞的生长,呈剂量与时间依赖性,不同浓度苦参碱组之间与不同作用时间组之间的差异均有显著性意义(P<0.01)。苦参碱诱导LNCaP细胞出现剂量依赖性G2/M期阻滞(P<0.01);细胞内AR的表达随苦参碱剂量依赖性减少(P<0.01)。结论:苦参碱通过下调细胞内AR表达和阻滞细胞周期进展来抑制LNCaP细胞的体外生长。     

氟他胺耐受前列腺癌动物模型的建立

目的建立SCID鼠前列腺癌氟他胺耐受模型。方法运用我们前期建立的氟他胺耐受前列腺癌细胞LNCaPflu(5×106个/0.1ml),结合应用Matrigel胶,将LNCaP细胞、LNCaPflu细胞分别各接种20只SCID雄鼠皮下,成瘤后将LNCaP细胞种植荷瘤鼠随机分为两组(LNCaP组、LNCaP/flu组),同时将LNCaPflu细胞种植荷瘤鼠也随机分为2组(LNCaPflu组、LNCaPflu/flu组),每组6只,其中LNCaP/flu组、LNCaPflu/flu组两组给予SCID鼠氟他胺20mg/kg体重皮下注射,每周2次,另2组作为对照组,动态观察肿瘤的生长状况。21d后测量瘤体大小,应用免疫组织化学方法检测种植瘤组织AR和PSA的表达。结果模型建立过程中,LNCaP细胞接种成瘤率75%(15/20),LNCaPflu细胞接种成瘤率60%(12/20),种植瘤组织组化染色AR均为阳性,而PSA均为阴性,未观察到肿瘤的远位转移。LNCaP组、LNCaPflu组、LNCaPflu/flu组3组间瘤重、瘤体积之间的差异无统计学意义(P>0.05),与LNCaP/flu组差异有统计学意义(P<0.05)。结论成功建立了前列腺癌细胞氟他胺耐受动物模型,为进一步研究并解决临床氟他胺耐受现象提供了重要的动物模型。     

人抑癌基因PTEN对前列腺癌细胞系生物学行为的影响

目的　探讨外源性人抑癌基因PTEN表达对前列腺癌细胞系LNCaP、DU 14 5细胞增殖和侵袭转移能力的影响。　方法　利用携带人PTEN基因的可调控性腺病毒 (Ad PTEN ) ,体外转染人前列腺癌细胞系LNCaP、DU 14 5,RT PCR、Westernblot检测目的基因不同水平的表达 ,通过细胞生长试验、流式细胞仪分析技术以及Boyden小室法检测LNCaP、DU 14 5转染前后细胞增殖、细胞周期、细胞凋亡和细胞体外侵袭力的变化。　结果　转染Ad PTEN后LNCaP、DU 14 5细胞的PTEN表达由阴性转为阳性 ,转染后对LNCaP、DU 14 5细胞生长有抑制作用 ,阻滞于G0 ～G1期 ,早期细胞凋亡率增加 ,LNCaP细胞 (6.89± 0 .51) % ;DU14 5细胞 (5.44± 1.13 ) % ,与对照组相比差异有显著性 ,Boyden小室法检测转染后体外侵袭力受到明显抑制。 　结论　重组腺病毒介导的人PTEN基因在体外对前列腺癌细胞系LNCaP、DU 14 5的细胞增殖和体外侵袭力有明显抑制作用 ,可望作为前列腺癌基因治疗的有效工具     

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.     

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.