膜截流分子量对新型生物人工肝支持系统内细胞材料影响的实验研究

目的 探索膜截流分子量对新型生物人工肝(bioartificial liver,BAL)支持系统内细胞材料功能的影响.方法 选用200×103和1200×103两种不同膜截流分子量的半透膜作为BAL隔离膜.正常比格犬接受新型BAL治疗6h,定时收集BAL系统中培养液.观察各组细胞活力及功能变化.结果 200×103组细胞活力保持在90％左右,明显高于1200×103组的22％.细胞功能检测显示,200×103组细胞白蛋白分泌水平及尿素合成分别为53.3 μg/106细胞和3.6 μg/106细胞,显著高于1200×103组的5.6 μg/106细胞和0.3 μg/106细胞.1200×103组反应器内免疫球蛋白分子浓度显著高于200×103组,免疫荧光试验进一步证实了上述结果.结论 降低BAL膜截流分子量可以有效减少免疫球蛋白分子的透过,从而维持BAL中细胞材料的功能.     

新型多层平板型生物人工肝体外支持系统治疗肝功能衰竭的临床研究

目的 评价新型多层平板型生物人工肝(BAL)体外支持系统治疗肝功能衰竭的临床效果及安全性.方法 2010年12月至2011年12月,有38例肝功能衰竭患者接受了新型多层平板型BAL治疗共计48例次,每次治疗时间为4h,于治疗前,治疗中,以及治疗后1、3、7和14d,抽取患者外周血监测肝功能和凝血功能等生化指标,并观察患者临床症状及体征的变化,以判定BAL的治疗效果.采用酶联免疫吸附试验法检测患者血浆及反应器中IgG、IgM及补体CH50的水平,采用聚合酶链反应检测外周血单个核细胞(PBMC)中猪内源性逆转录病毒(PERV) DNA、猪特异性细胞色素B(SsCytB)基因序列及逆转录酶的活性等,以评估BAL治疗的安全性.结果 大部分患者接受BAL治疗后感觉良好,精神状态、临床症状、各项指标较治疗前均有所缓解或明显改善,未发生严重不良反应.38例患者中,临床治愈9例,好转25例,治愈好转率为89.5％(34/38),治疗无效4例;有7例患者经BAL治疗后病情好转,顺利等到供肝接受了肝移植.治疗期间,患者血浆IgG、IgM和CH50水平均未出现明显变化,仅补体CH50在治疗1h时出现一过性下降,随后很快恢复正常水平;反应器内未检测出IgG,仅治疗4h时检出极少量IgG,治疗4h内均未检测出IgM.各时间点患者PBMC均未检测到PERV DNA,且患者血浆中均未检测到猪特异性SsCytB基因序列和逆转录酶活性.结论 新型多层平板型BAL体外支持系统对肝功能衰竭患者具有良好的临床治疗效果和安全性,其在患者等待供肝期间也可作为良好的过渡治疗手段.     

采用纳米支架材料的新型多层平板型生物人工肝的免疫安全性研究

目的：探讨新型生物人工肝（BAL）系统的免疫安全性。 方法：采用自制纳米支架材料的新型多层平板型生物反应器与猪肝细胞-骨髓间充质干细胞共培养体系构建新型的BAL系统。正常比格犬接受新型BAL体外循环灌注6 h,期间定时收集BAL系统中的血液及培养液。ELISA法检测培养液及术前、术中、术后血浆中IgG,IgM及CH50（C3）水平;检测外循环前后的血常规情况;免疫荧光法检测术后反应器内细胞材料表面以及犬心、肝、脾、肺、肾等器官免疫蛋白的沉积情况。 结果：经过6 h的体外循环灌注,犬体内IgG,IgM免疫抗体水平术中、术后均未出现明显的升高或下降,而术中补体CH50水平出现一过性下降,但很快恢复至正常水平,且并未发生严重的过敏反应及排斥反应,反应器内培养液中检出极少量的IgG和CH50;血常规检测显示,术后白细胞、血小板及淋巴细胞未出现明显的升高或降低;术后反应器内细胞材料表面仅有微量的IgG与C3沉积,各重要脏器均未检测到IgG,IgM及补体C3的沉积。 结论：新型BAL系统具有良好的免疫安全性。     

异种肝细胞移植缓解大鼠急性肝功能衰竭及其排斥反应观察

目的探讨异种肝细胞移植对大鼠急性肝功能衰竭防治效果及其免疫排斥反应。方法将异种豚鼠肝细胞,90%肝除术前1d植入大鼠脾脏内。观察受试大鼠存活时间,及切肝术后24h血生化改变。另外观察植入肝细胞被排斥情况及受体CH50、异种抗体IgG、IgM水平变化。结果(1)中位存活时间,对照组为21h,同种组为56h,异种组为40h。同种组存活时间较对照组延长(P<0·01),异种组亦延长(P<0·05)。(2)异种组血糖和凝血酶原时间改善较明显(P<0·05),同种组谷丙转氨酶、总胆红素、血糖、凝血酶原时间都有明显改善(P<0·05或P<0·01)。(3)受体CH50和异种抗体IgM水平下降与植入异种肝细胞排斥过程同步。结论异种肝细胞移植对大鼠急性肝功能衰竭有防治作用,补体和异种抗体IgM与排斥反应关系密切。     

生物人工肝的研究进展

肝移植是治疗急慢性肝功能衰竭最有效的方法,但是,由于供肝缺乏,必需寻求终未性肝病替代疗法.其中主要方法之一是体外生物人工肝支持系统,简称生物人工肝(bioartificial liver, BAL),发展至今已有40多年.临床试验证明BAL能促进肝功能衰竭病人的恢复,或过渡到肝移植.生物反应器是BAL的核心部件,生物反应器设计的主要目的在于保持肝细胞活力和功能,且不妨碍肝细胞营养及代谢产物的交换,同时还能起到治疗作用.细胞材料是BAL治疗基础,维持细胞活率和功能对BAL功效有决定性作用.本文就生物人工肝装置在实验和临床试验中的研究进展作一综述.……     

康肾片对老年维持性血透患者细胞免疫与体液免疫及补体系统的影响

目的 :探讨康肾片调节老年维持性血透患者免疫功能的作用机理。方法 :将老年肾衰竭患者 4 7例分为治疗组 35例、对照组 12例 ,均予常规血液透析。治疗组在透析的同时予口服康肾片。观察各组治疗前后CD3 + 、CD4+ 、CD8+ 、CD4+ /CD8+ ,IL - 1、IL - 2、IL - 6 ,IgG、IgA、IgM ,C3 、C4、CH50 水平的变化。结果 :治疗组治疗后 6个月CD3 + 、CD4+ 、CD4+ /CD8+ ,IL - 2 ,C3 、C4、CH50 明显上升 ;同时CD8+ 、IL - 1、IL - 6明显下降 ;IgG、IgA、IgM与治疗前相比则无明显变化 (P >0 .0 5 )。对照组治疗前后对比无显著性差异。结论 :康肾片可明显提高老年维持性血透患者CD3 + 、CD4+ 、CD4+ /CD8+ ,IL - 2 ,C3 、C4、CH50 异常降低的水平 ;可下调异常增高的CD8+ 、IL - 1、IL - 6的水平 ,具有调节老年维持性血透患者免疫失调的作用     

生物人工肝系统治疗对急性肝衰竭犬血清内毒素的影响

目的　探讨生物人工肝 (BAL )系统治疗急性肝衰竭 (ALF )的效果及其与内毒素的关系。方法　采用门腔分流及胆总管结扎切断术建立犬ALF模型。 10只实验动物随机分为两组 ,即BAL治疗组和对照组 (未行BAL治疗组 )。BAL每次循环 5h。检测两组建模前 ,以及循环前后的血清内毒素、谷丙转氨酶 (ALT )和总胆红素 (TB)。结果　治疗组建模前、循环前和循环后血清内毒素分别为 0 .2 84EU /ml ,0 .5 2 6EU /ml ,0 .416EU /ml ;循环前血清内毒素较建模前明显升高 (P <0 .0 5 ) ,循环后又明显降低 (P <0 .0 5 ) ;对照组循环前血清内毒素显著高于建模前 (P <0 .0 5 ) ,循环前后血清内毒素无明显变化 (P >0 .0 5 )。治疗组循环后血清ALT和TB较循环前明显下降 (P <0 .0 5 ) ;对照组循环前后ALT和TB无明显变化 (P >0 .0 5 )。结论　BAL治疗能降低ALF犬血清内毒素含量。     

腹腔镜手术对子宫内膜异位症患者炎症因子及免疫球蛋白的影响

目的探讨腹腔镜手术对子宫内膜异位症患者炎症因子及免疫球蛋白的影响。方法根据手术方式不同将122例宫内膜异位症患者分为2组,各61例。对照组行开腹手术,观察组行腹腔镜手术。对比2组患者手术前后炎症因子及免疫球蛋白水平变化情况。结果术前2组hs-CRP、TNF-α、IgM、IgG水平比较,差异无统计学意义(P0.05)。术后2组hs-CRP、TNF-α水平均上升、IgM、IgG水平均下降,但观察组炎症因子水平上升幅度及免疫球蛋白水平下降幅度均明显低于对照组,差异有统计学意义(P0.05)。结论腹腔镜手术治疗子宫内膜异位症,虽对患者炎症因子及免疫球蛋白水平造成一定影响,但相比于传统手术较小。     

抗炎灵对腹部外科SIRS/MODS患者免疫功能的影响

目的：动态研究观察抗炎灵对腹部外科SIRS／MODS患者免疫功能的影响。方法：以腹部外科手术SIRS／MODS52例患者为研究对象,按入院时间分为对照组21例和抗炎灵治疗组31例,分别于术后1、3、7d观察血清I gA,IgG,IgM,C3,C4水平。结果：血清IgG,IgM,IgA和补体C3、C4后逐渐上升,于第3d时IgG,IgM,IgA两组有显著差别（P＜0．05）,于第7d时,C3、C4两组有差异（P＜0．05）,治疗组上升较快,结论：抗炎灵能提高机体免疫能力,对SIRS／MODS有一定的治疗作用。     

生物人工肝研究现状及进展

肝功能衰竭病情凶险,进展迅速,预后较差,各种药物治疗效果不佳,肝移植是治疗肝衰竭病人惟一有效的手段.但是,由于供体器官缺乏、费用高昂、需长期使用免疫抑制剂等原因,病人往往在等待供体过程中由于病情进展而迅速死亡,生物人工肝(bioartificial liver,BAL)可为病人提供短暂的肝功能支持,从而成为人们研究的焦点.本文从细胞来源、细胞培养方式及生物反应器三方面综述BAL目前的研究现状及近年来的进展.     

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.     

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.     

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.     

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.     

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.     

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.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.