肝再生过程中转化性生长因子β对肿瘤细胞生长的促进作用

目的 观察转化性生长因子β（ＴＧＦ－β）对肝癌细胞的促进作用。方法 ＢＵＦ大白鼠在接种７３１６Ａ肝癌细胞的同时应用人γＴＧＦ－β１治疗，并于接种后５～２０天测量肿瘤体积，γＴＧＦ－β１还分别加入混合淋巴细胞培养（ＭＬＲ）及７３１６Ａ肝癌细胞培养中，结果 大白鼠经ＴＧＦ－β治疗组的肿瘤体积显著大于对照组（Ｐ〈０．０１）；ＴＧＦ－β明显抑制了Ｔ淋巴细胞的ＭＬＲ反应（Ｐ〈０．０５），但对７３１６Ａ肝癌细     

不同作用时间内表皮生长因子对肝癌细胞凋亡的影响

目前研究证实众多因素可以诱导肝癌细胞凋亡,如ＴＧＦ、ＩＬ－２、ＴＮＦ等,也有学者报道营养缺乏是诱导肿瘤细胞凋亡的重要因素,为此我们用无血清培养诱导人肝癌细胞株ＳＭＭＣ－７７２１凋亡,并以此为模型研究表皮生长因子（ＦＧＦ）对肝癌细胞凋亡的影响。 材料与方法 １．细胞培养 人肝癌细胞株ＳＭＭＣ－７７２１购自中国科学院上海细胞所,用含１０％小牛血清（华美公司）ＲＰＭＩ－１６４０（ＧＩＢＣ公司）培养液培养于３７℃、５％ ＣＯ培养箱中,常４８ｈ更换培养液。 ２．扫描电镜 生长于盖玻片上的贴壁细胞（无血清培养）经…     

肝癌病人树突状细胞诱导高效而特异的抗肝癌免疫

目的 以肝癌病人树突状细胞（ＤＣ）体外诱导抗肝癌免疫。方法 自肝癌病人外周血中分离出单个核细胞（ＰＢＭＣ０;以人肝癌细胞系ＨｅｐＧ２肿瘤细胞的肿瘤相关抗原（ＴＡＡ）激活ＤＣ;以粒／巨噬细胞集落刺激因子（ＧＭ－ＣＳＦ）及白介素４（ＩＬ－４）联合刺激ＰＢＭＣ中ＤＣ;ＤＣ诱导自体Ｔ淋巴细胞增殖,分化为细胞毒性Ｔ细胞（ＣＴＬ）;检测ＣＴＬ及其上清液对ＨｅｐＧ２,ＢＥＬ－７４０２,ＬＯＶＯｅｙ ＨＯＳ－８６     

肝癌患者转化生长因子—β1及其受体的表达和意义

目的 探讨肝癌患者转化生长因子－β１（ＴＧＦ－β１）及其受体的表达情况和意义。方法 酶联免疫吸附法检测２７例行胆囊切除术者（对照组）和３６例肝癌患者（肝切除组）肝切除手术前后血清ＴＧＦ－β１浓度;免疫组织化学法检测３６例肝癌和癌周组织标本中相关受体的表达情况。结果 肝癌患者血清ＴＧＦ－β１浓度较对照组显著升高（Ｐ〈０．０５）;患者肝切除术后血清ＴＧＦ－β１浓度较术前有显著升高（Ｐ〈０．０１）,而胆     

B7修饰的肝癌细胞疫苗对细胞因子产生的研究

目的 研究Ｂ７基因修饰的肝癌细胞疫苗刺激产生细胞因子（ＩＬ－２,ＴＮＦ－α和Ｇ－ＣＳＦ）的能力。方法 应用逆转录病毒载体,将Ｂ７－１,Ｂ７－２基因导入小鼠肝癌细胞Ｈｅｐａｌ－６细胞株中,获高表达Ｂ７分子的阳性细胞克隆,经丝裂霉素Ｃ（ＭＭＣ０处理,制备肿瘤细胞疫苗（ＴＣＶ）,观察ＴＣＶＢ７体内外对细胞因子ＩＬ－２,ＴＮＦ－α和Ｃ－ＣＳＦ产生的影响。结果 （１）ＴＣＶＢ７体外能刺激脾细胞分泌细胞因子Ｉ     

经肝动脉化疗栓塞后TGF—β1,TGF—α在肝癌细胞凋亡中的作用

目的 探讨经肝动脉化疗栓塞后ＴＧＦ－β１、ＴＧＦ－α在肝癌细胞凋亡中的作用。方法应用免疫组织化学方法检测１９例未经肝动脉化疗栓塞（ＴＡＣＥ）和３６例ＴＡＣＥ治疗的肝癌组织中ＴＧＦ－β、ＴＧＦ－α的表达,采用ＩＳＥＬ法检测肝癌细胞凋亡。结果经ＴＡＣＥ治疗和未经ＴＡＣＥ治疗的肝癌组织中ＴＧＦ－β１表达率分别为８６．１１％和３６．８４％;ＴＧＦ－α表达率分别为３６．１１％和８４．２１％;肝癌细胞凋亡指数分别为０．００８８和０．１９０１。结论 经ＴＡＣＥ治疗后ＴＧＦ－β１表达增强,促进了肝癌细胞凋亡。ＴＧＦ－α主要与肝癌细胞增殖有关,其表达减弱亦可能促进了肝癌细胞凋亡。     

TGF—β1,PAI—1与糖尿病肾病

糖尿病时,多种机制引起转化生长因子β１（ＴＧＦ－β１）和纤溶酶原激活物抑制物１（ＰＡＩ－１）在肾脏局部过度表达。ＴＧＦ－β１有抑制细胞有丝分理解,促进细胞外基质（ＥＣＭ）合成,抑制其降解的作用,ＰＡＩ－１则抑制ＥＣＭ降解,二者共同作用,导致肾脏肥大和ＥＣ积聚。近年来,二者对糖尿病的诊断和治疗的临床意义备受人们的关注。     

内皮素对肾小球系膜细胞转化生长因子基因表达的影响

观察肾小球系膜细胞（ＭＣ）的转化生长因子（ＴＧＦ－β）的基因表达，以及内皮素（ＥＴ）对ＴＧＦ－β基因表达的影响。方法应用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）及半定量ＲＴ－ＰＣＲ方法对体外培养的大鼠ＭＣ进行了ＴＧＦ－β基因表达的定量检测。结果ＭＣ有ＴＧＦ－β的基因表达，并且ＥＴ对ＴＧＦ－β的基因表达有上调作用。结论ＴＧＦ－β是ＭＣ的又一个自分泌因子，ＥＴ和ＴＧＦ－β可能有协同作用而引起ＭＣ增生和系膜基质（ＭＭ）的增多，在肾小球肾炎和肾小球硬化的病理过程中，具有一定意义     

牛血小板TGF－β提取、纯化及其诱导小鼠股骨成骨作用

ＴＧＦ－β广泛存在于多种正常组织细胞及转化细胞中，不同种属间高度同源。目前认为血小板是ＴＧＦ－β最好的组织来源。本实验以牛血小板为原料，采用酸醇抽提方法，提取血小板蛋白。相继进行两次ＢｉＯ－ＧｅｌＰ６０柱层析，分离纯化出其中分子量为２５ｋＤａ的ＴＧＦ－β。雄性昆明小鼠４０只，随机分成实验组和对照组。在实验组动物股骨中下段前方骨膜下注射ＴＧＦ－β溶液２０μｌ（４００ｎｇ）；在对照组相应部位注射ＰＢＳ溶解的牛血清白蛋白（ＢＳＡ）２０μｌ（ｌ００μｇ）。结果显示，小鼠股骨干骨膜下每日注射ＴＧＦ－β，导致其骨膜间充质细胞增殖、软骨生成及软骨内化骨效应；而对照组注射ＢＳＡ后，在注射部位骨膜间充质细胞无明显增殖反应。实验表明，ＴＧＦ－β作用于小鼠股骨干骨膜间充质细胞使之增殖，分化成软骨细胞和成骨细胞，通过软骨内化骨作用形成新的骨质。这与正常骨折愈合过程相一致；即是说，外源性的ＴＧＦ－β可以启动骨生成过程，意味着ＴＧＦ－β在骨折修复及骨移植方面有潜在性应用前景。     

肝癌特异性细胞毒 T 淋巴细胞的实验及临床研究

诱导肿瘤特异性细胞毒性Ｔ细胞（ＴＳ－ＣＴＬｓ），观察其体外、体内的抗肿瘤作用及其特异性；评价其抗肝癌术后复发的临床应用价值。方法：用细胞因子体外短期刺激方法提高肝癌细胞的免疫原性，再与肿瘤浸润Ｔ细胞共同培养，辅以ＣＤ２８单抗共刺激，诱导ＴＳ－ＣＴＬｓ，检测其体内外抗肝癌作用及其效应机制；大量扩增后回输患者，观察其免疫学指标的变化并随访其术后复发情况。结果：体外研究表明，肝癌细胞经ＩＦＮ－γ、ＴＮＦ－α诱导后ＭＨＣＩ类分子，ＩＣＡＭ－１及Ｂ７分子的表达增高，用此细胞辅以ＣＤ２８单抗刺激诱导产生的ＴＳ－ＣＴＬｓ体现了高度的对自体肝癌的杀伤活性及特异性，其杀伤活性由ＴＣＲ－ＣＤ３复合物、ＣＤ８、ＬＦＡ－１、ＩＣＡＭ－１及ＭＨＣＩ类分子所介导。体内研究的结果表明，ＴＳ－ＣＴＬｓ对ＳＣＩＤ小鼠人肝癌模型具有显著的抑瘤作用。１２例初步临床应用的结果表明，ＴＳ－ＣＴＬ对于提高机体的Ｔ细胞免疫功能，对于预防肝癌术后复发均具有良好作用，值得进一步深入研究和应用。结论：ＴＳ－ＣＴＬｓ作为一种新的肿瘤特异性免疫治疗方法可望进一步提高肝癌和其它实体肿瘤的外科综合治疗水平。     

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.     

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.     

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.