丙型肝炎病毒核心蛋白通过活化stat3通路促进肝癌细胞上皮间质转化的研究

目的探讨丙型肝炎病毒核心蛋白（HCVc）对肝癌细胞信号转导子和转录激活子3（stat3）通路及上皮间质转化（EMT）的影响。 方法将含HCVc基因序列的重组质粒pEGFP-N3-HCVc转染人肝癌细胞HepG2,Real-Time PCR和Western blotting检测HCVc、总stat3、磷酸化stat3（p-stat3）及EMT指标蛋白E-cadherin、Vimentin、Snail的表达,划痕实验及Transwell实验检测细胞迁移和侵袭情况。 结果划痕实验及Transwell实验结果显示,过表达HCVc可增强HepG2细胞的迁移和侵袭能力;stat3通路抑制剂AG490处理可抑制HepG2细胞的侵袭能力。RT-PCR和Western blotting结果显示,过表达HCVc后,HepG2细胞中p-stat3、Vimentin及Snail在表达升高,E-cadherin表达下降;AG490处理可下调p-stat3、Vimentin及Snail表达,增强E-cadherin表达。 结论HCVc可活化stat3通路促进肝癌细胞上皮间质转化,增强肝癌细胞的迁移和侵袭能力。     

携带IL-13基因大鼠肝干细胞系的建立

目的 构建包含IL-13基因片段的慢病毒载体,培养IL-13基因工程大鼠肝干细胞(肝卵圆细胞,HOC,WB-F344细胞),将IL-13基因重组至WB-F344细胞中,使之可分泌大鼠IL-13.方法 人工合成大鼠IL-13基因,利用pWPXL-MOD(TG-005)载体构建包含大鼠IL-13基因片段的质粒; 制备慢病毒穿梭质粒及其辅助包装元件载体质粒,四质粒载体(组成为pRsv-REV、pMDlg-pRRE、pMD2G及目的穿梭质粒)分别进行高纯度无内毒素抽提,共转染293T细胞,培养48 h后,收集富含慢病毒颗粒的细胞上清液,对其浓缩后得到高滴度的慢病毒浓缩液,定量PCR检测病毒滴度.将构建好的慢病毒感染WB-F344细胞,5 d后采用real-time PCR检测WB-F344细胞中IL-13的表达水平,Western blot检测重组蛋白表达水平.结果 成功构建了IL-13过表达慢病毒载体,并获得IL-13基因工程大鼠肝干细胞; 将IL-13基因重组至WB-F344细胞基因组中,并可在细胞中进行转录,慢病毒感染WB-F344细胞存在IL-13 mRNA表达,可分泌大鼠IL-13.结论 构建的基因工程WB-F344细胞能显著分泌大鼠IL-13,感染后的WB-F344细胞的IL-13表达水平显著高于感染前,满足动物实验要求.     

大鼠GSK3β基因RNAi腺病毒载体的构建与鉴定及其对肝卵圆细胞增殖的促进作用

目的构建并鉴定特异性大鼠糖原合成酶激酶3β(GSK3β)基因siRNA腺病毒载体,观察其对肝卵圆细胞系WB-F344增殖的影响。方法用DNA重组技术将针对GSK3β基因不同部位所设计的2对shRNA序列克隆到高效RNAi真核表达质粒载体pGenesil-1.1中,构建shRNA表达载体pGenesil-1.1-GSK3β。分别酶切重组质粒及pDC312载体,转化连接,构建腺病毒载体pDC312-GSK3β,PCR扩增与鉴定。脂质体法介导腺病毒载体与骨架质粒pPE3-F11共转染293细胞,包装产生腺病毒颗粒AdD C3 12-GSK3β并测定滴度。取病毒上清感染WB-F34 4细胞,荧光显微镜观察细胞荧光含量,Western blotting检测GSK3β蛋白表达。CCK-8测定转染前后WBF-344增殖变化。结果经PCR酶切及Western blotting技术证实成功构建了针对大鼠GSK3β基因RNAi质粒pGenesil-1.1-GSK3β及GSK3β基因RNAi重组腺病毒载体AdDC312-GSK3β。Western blotting证实该重组腺病毒载体可抑制WBF-344细胞GSK3β的表达。CCK-8结果显示干扰GSK3β可促进WBF-344细胞增殖。结论成功构建了针对GSK3β基因RNAi的腺病毒载体,并在大鼠肝卵圆细胞系WBF-344中稳定表达,促进细胞增殖。     

TGF-β1诱导胃癌细胞上皮间质转化及其上调CD44表达的实验研究

目的 观察TGF-β1诱导胃癌SGC7901细胞发生上皮间质转化及其对胃癌细胞生物学特性与肿瘤起始细胞特性的影响.方法 TGF-β1处理胃癌SGC7901细胞后,观察其形态学变化;CCK-8法检测细胞增生能力;划痕实验及transwell实验检测细胞迁移与侵袭能力;免疫荧光法检测上皮钙黏素及间质钙黏素表达的变化;逆转录PCR法与免疫蛋白印迹法检测上皮间质转化相关因子及CD44的表达.结果 TGF-β1处理SGC7901细胞后,细胞形态由上皮细胞形态向间质细胞样形态转变;TGF-β1处理后,处理组划痕愈合程度明显高于对照组(P＜0.05),处理组穿膜细胞数目(107.67±5.48)显著高于对照组(53.33±8.47,P＜0.05),TGF-β1处理组SGC7901细胞上皮钙黏素表达显著降低(P＜0.05),间质钙黏素(P＜0.05)与Snail(P＜0.05)表达显著增加,肿瘤起始细胞相关标志物CD44表达显著增加(P＜0.05).结论 TGF-β1可诱导胃癌SGC7901细胞发生上皮间质转化,增加CD44表达,抑制胃癌细胞增生,促进其侵袭和迁移.     

基于iTRAQ技术的WB-F344细胞向胆管细胞分化过程中的蛋白质组学研究

目的 应用iTRAQ技术观察WB-F344细胞向胆管细胞分化过程中蛋白质表达组的变化.方法 将WB-F344细胞接种于丁酸钠分化体系中进行分化诱导,提取不同时间点(第0、2、4、6天)的分化蛋白以iTRAQ试剂标记后进行质谱检测并以软件分析差异表达的蛋白质.结果 iRAQ试剂标记的WB-F344分化细胞蛋白质表达谱分析...     

异黏蛋白表达在胃腺癌中的临床意义及其对侵袭转移的影响

目的 探索异黏蛋白在胃癌组织中的表达、调控机制及临床意义.方法 免疫组化染色检测68例胃癌组织标本异黏蛋白和E-cadherin表达,并利用x2检验等分析其对各临床病理特征和预后的影响.Transwell实验和划痕实验检测胃癌细胞侵袭迁移能力.利用小干扰RNA(siRNA)技术,特异性干扰异黏蛋白蛋白表达,观察异黏蛋白对MKN45细胞侵袭迁移的影响并探讨其调控机制.结果 胃癌组织中异黏蛋白阳性表达与肿瘤浸润深度(P =0.029)、淋巴结转移(P=0.001)、TNM分期(P=0.014)及抑制E-cadherin表达有关(P=0.001).同时,异黏蛋白阳性患者预后比其阴性患者预后更差.当下调MKN45细胞异黏蛋白表达时,则其E-cadherin表达增高,N-cadherin、Slug及Snail表达下降,且细胞的侵袭能力(P=0.027)和迁移能力(P=0.008)下降.结论 异黏蛋白通过转录因子Slug、Snail而非Twist诱导上皮间质转化过程促进胃癌的转移,并降低患者术后生存率.     

Tim-3在肝癌细胞上皮间质转化及转移中的作用机制

目的:探讨Tim-3与肝癌细胞发生上皮间质转化(EMT)的关系及对肝癌细胞侵袭和转移能力的影响。方法:培养正常肝细胞L02和肝癌细胞SMMC-7721,RT-PCR检测Tim-3表达差异,将SMMC-7721分为3组,对照组:未接受转染的SMMC-7721;实验组转染Tim-3 siRNA细胞低表达Tim-3;阳性对照组转染PEX-3-hTim-3过表达质粒细胞高表达Tim-3。应用RT-PCR、Western blot检测3组肝癌细胞Tim-3及EMT相关基因:E-cadherin、N-cadherin、MMP-9、Twistl、Slug、Snail、Smad mRNA和蛋白的表达。通过Transwell小室侵袭实验检测3组肝癌细胞迁移和侵袭能力改变;分析Tim-3表达与EMT相关基因表达的相关性。结果:(1)与正常肝细胞L02比较;Tim-3在肝癌细胞中高表达(P<0.05);(2)RTPCR和Western bolt结果提示,实验组上皮标志物E-cadherin表达较对照组明显上升(P<0.05),而间质标志物N-cadherin、MMP-9、Twistl、Snail、Slug、Smad表达较对照组下降(P<0.05),提示EMT受到抑制;阳性对照组中E-cadherin表达较对照组下降(P<0.05),N-cadherin、MMP-9、Twist1、Snai1、Slug、Smad表达较对照组上升(P<0.05),促进了肝癌EMT;(3)Transwell迁移实验中,实验组与对照组和阳性对照组相比较,肝癌细胞迁移和侵袭细胞数明显减少,3组之间比较差异均有统计学意义(P<0.05),实验说明Tim-3表达水平的改变,影响肝癌的迁移和侵袭性;(4)Tim-3的表达与EMT标志物的表达做相关性分析显示,Tim-3的表达与E-cadherin的表达呈负相关(P<0.05),与N-cadherin、MMP-9、Twist1、Snai1、Slug、Smad的表达呈正相关(P<0.05)。结论:Tim-3是肝癌细胞EMT的潜在诱导者,抑制Tim-3的表达,同时抑制肝癌细胞EMT的发生,肝癌细胞迁移和侵袭能力下降。因此,Tim-3有望成为今后的临床抗肿瘤药物新的治疗靶点用于改善和评估患者预后。     

eIF5A-2在非小细胞肺癌上皮间质化过程中的作用机制

目的 探讨真核细胞翻译起始因子5A-2(eIF5A-2)的表达在非小细胞肺癌(NSCLC)上皮间质化(EMT)过程中的作用及其机制.方法 通过Westrn-blotting和免疫荧光检测细胞表型变化,利用siRNA转染下调eIF5A-2表达后再以Western-blotting和免疫荧光检测细胞表型的改变.用TGF-β1刺激诱导NSCLC细胞系NCI-H358和HCC827发生EMT后并利用Western-blotting检测eIF5A-2的表达.结果 NCI-H358和HCC827细胞系低表达eIF5A-2,为上皮表型,而NCI-H1299细胞高表达eIF5A-2,为间质表型.eIF5A-2 siRNA干扰后可以改变NCI-H1299细胞的间质表型.NCI-H358和HCC827细胞经TGF-β1诱导后可发生EMT变化,而eIF5A-2 siRNA干扰后则可防止这种变化的发生.结论 在不同的NSCLC细胞系中,间质表型细胞较上皮表型者高表达eIF5A-2.TGF-β1可诱导上皮表型细胞发生EMT,而干扰eIF5A-2则可阻止EMT的发生.     

曲古霉素A对小鼠骨髓源性树突状细胞免疫功能的影响

有研究结果表明,树突状细胞(DC)是一种异质性的细胞群体,在不同的成熟阶段具有不同功能,其中处于未成熟阶段DC可诱导免疫耐受,而成熟DC诱导机体免疫应答[1].组蛋白去乙酰化酶抑制剂(HDACi)主要作为抗癌药物在临床使用,研究结果显示其在非细胞毒性剂量时还具有抗炎、抗过敏等功效[2].本实验旨在观察HDACi曲古霉素A(TSA)在体外对小鼠骨髓源性DC表型及功能的影响.     

罗格列酮对肾小管上皮细胞间质转化的影响

目的探讨罗格列酮对转化生长因子 β（TGF β）诱导的肾小管上皮细胞间质转化（EMT）过程的影响。方法体外培养人肾小管上皮细胞HK 2，并给予不同浓度TGF β及罗格列酮处理，观察HK 2形态学变化，利用免疫印迹检测过氧化物酶体增殖激活物受体γ（PPARγ）、SMAD家族成员2/3、钙粘附蛋白 E（E cadherin）及波形蛋白（Vimentin）水平变化，通过实时荧光定量聚合酶链反应（PCR）术检测PPARγ、E cadherin、Vimentin、锌指转录因子Snail及Slug的mRNA水平变化，并利用双荧光素酶报告基因检测TGF β及罗格列酮对E cadherin启动子活性的影响。结果TGF β可诱导HK 2细胞发生伪足增多变长、细胞间隙变大等EMT样形态学变化，进而激活TGF β下游的SMAD2/3信号通路，导致上皮细胞标志E cadherin表达明显减少，伴有间质细胞标志的Vimentin表达增高，转录因子Snail及Slug的mRNA水平分别升高6倍以上，伴随E cadherin启动子活性下降70%。罗格列酮可以显著抑制上述TGF β诱导的EMT过程，表现为HK 2细胞足减少变短，细胞间隙变小等，同时伴有E cadherin表达增加，Vimentin表达降低，Snail及Slug的mRNA水平明显降低，E cadherin启动子活性恢复到对照组水平。结论罗格列酮可通过激活PPARγ促进E cadherin转录活性及蛋白表达，拮抗TGF β诱导的EMT过程。     

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.     

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.     

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.     

Intrathecal administration of sameridine to patients subjected to arthroscopic knee joint surgery

Background: Sameridine, a new substance with both local anesthetic and opioid effects, was administered intrathecally for the first time to humans, i. e. in patients subjected to arthroscopic knee joint surgery.
Method: A dose-escalating (10, 15, 20 and 25 mg), open study was performed in 33 patients. Only two patients were included in the 25 mg group.
Results: Sameridine provided good quality of surgical anesthesia in all patients except those receiving 10 mg. The maximum level of sensory block, Th5–Th7, was reached within 30 min with a median duration of 3.6–3.9 h. The motor block was more profound with increasing dose, but never lasted longer than the sensory block. The influence on heart rate and blood pressure was minor and atropine and ephedrine were needed in four patients. No clinically significant ECG-changes were detected and no arrhythmias were recorded. Oxygen saturation and respiratory rate did not decrease in a clinically significant way and were not affected by concomitant morphine given i. v. postoperatively. There were few side-effects, the most frequent being mild pruritus (10/33).
Conclusion: Sameridine provided clinically adequate anesthesia for the patients receiving the doses of 15, 20 and 25 mg. Further studies are needed to evaluate the substance and it is of great interest to clinically investigate the opioid component with respect to postoperative analgesia.     

Reduction of Plasma Fibrinogen, Immunoglobulin G, and Immunoglobulin M Concentrations by Immunoadsorption Therapy with Tryptophan and Phenylalanine Adsorbents

Abstract Immunoadsorption (1A) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session 1 plasma volume (2.8 ± 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonpara-metric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.