胃癌及癌前病变组织中幽门螺杆菌感染与NOD2和TLR9蛋白表达的相关性

目的 研究NOD2和TLR9蛋白在胃癌及癌前病变组织中的表达情况以及幽门螺杆菌(Hp)感染对该蛋白表达的影响.方法 用C13呼气试验和快速尿素酶试验确定感染情况,用免疫组化法测定40例慢性浅表性胃炎,84例慢性萎缩性胃炎,48例胃溃疡,80例胃腺癌组织中NOD2和TLR9蛋白的表达情况.结果 在慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡、胃腺癌中NOD2阳性表达率分别为35%、21%、33%、40%.TLR9阳性表达率分别为15%、12%、21%、22%.在同一病变中Hp阳性组NOD2及TLPO表达强于Hp阴性组,其中Hp阳性的慢性浅表性胃炎、胃溃疡、肠上皮化生、中重度不典型增生和胃癌组织中NOD2表达与Hp阴件组比较差异有统计学意义(P<0.05).结论 胃腺癌、癌前病变以及幽门螺杆菌感染能增强胃上皮细胞中NOD2和TLPO蛋白的表达,提示二者在胃黏膜天然免疫过程中可能起到重要作用.     

胃粘膜病变中人端粒酶催化亚单位、c-myc蛋白的表达及其相互关系

目的探讨胃粘膜病变中人端粒酶催化亚单位(humantelomerasecatalyticsubunit,hTERT)的表达状况及其与c-myc蛋白表达的关系。方法应用免疫组织化学技术检测45例慢性胃炎和19例胃癌中hTERT和c-myc蛋白的表达。结果hTERT蛋白的表达率在胃癌组织中显著高于不典型增生、肠化生和萎缩性胃炎组织(P<0.05);在不典型增生组织中显著高于肠化生和萎缩性胃炎组织(P<0.05);在肠化生组织中显著高于萎缩性胃炎组织(P<0.05)。c-myc蛋白的表达率在胃癌组织中显著高于不典型增生、肠化生和萎缩性胃炎组织(P<0.05);在不典型增生组织中显著高于肠化生和萎缩性胃炎组织(P<0.05);在肠化生组织中显著高于萎缩性胃炎组织(P<0.05)。hTERT蛋白表达率在c-myc蛋白阳性患者中显著高于c-myc蛋白阴性患者(P<0.01)。结论在胃癌和胃癌前病变阶段,端粒酶(telomerase)与c-myc均可能发挥重要作用,促进了胃癌的发生、发展;c-myc表达增加可能是胃粘膜上皮细胞端粒酶激活的主要机制之一。     

转录因子FOXO4与胃癌及Hp感染关系的临床研究

目的:探讨FOXO4在胃癌发生过程中的表达、临床意义及其与幽门螺杆菌(Hp)感染的关系。方法:应用免疫组织化学SP法分别检测16例正常胃黏膜、26例慢性萎缩性胃炎伴肠上皮化生、36例异型增生胃黏膜及60例胃腺癌组织中FOXO4的表达,并检测患者Hp感染状况。结果:FOXO4在正常胃黏膜、慢性萎缩性胃炎伴肠上皮化生、异型增生胃黏膜及胃腺癌组织中的阳性率分别为100%、84.6%、69.4%和40.0%,胃腺癌组阳性率显著低于正常对照组(P<0.01)。FOXO4的阳性率在高、中分化和低分化型胃腺癌组织中呈现递减趋势,且其表达和淋巴结转移密切相关(P<0.05)。慢性萎缩性胃炎伴肠上皮化生及胃腺癌组织中FOXO4表达与Hp感染之间均无明显相关性(P均>0.05)。癌前病变组织中FOXO4表达与Hp感染率之间呈明显正相关(P<0.01)。结论:在胃黏膜癌变过程中,FOXO4的表达和作用逐渐下调;在癌前病变组织中FOXO4表达和Hp感染密切相关。     

RNA干扰技术对大肠癌细胞人端粒酶逆转录酶基因的抑制作用

目的 观察RNA干扰对大肠癌细胞中人端粒酶逆转录酶基因(hTERT gene)的抑制效应.方法 大肠癌细胞株HT-29分为Control组、N-hTERT组、Lipofectamine组和sihTERT组;将靶向于hTERT基因的小干扰RNA,转染大肠癌细胞;分别检测大肠癌细胞转染前后的端粒酶活性,hTERTmRNA和蛋白水平,细胞生长增殖和凋亡情况.结果 sihTERT转染大肠癌细胞效率为60%;sihTERT组的端粒酶活性值、hTERT mRNA表达、hTERT蛋白表达、细胞凋亡率分别为0.73±0.14、0.47±0.08、0.37±0.07、49.5%,sihTERT组与其他三组比较差异有统计学意义(P<0.01).结论 靶向于hTERT的siRNA能特异性沉默大肠癌细胞hTERT基因,下调hTERT基因mRNA及蛋白表达水平,降低端粒酶活性,抑制癌细胞生长增殖从而促进大肠癌细胞凋亡.     

胃癌组织中端粒酶逆转录酶和hMSH2蛋白表达与幽门螺杆菌感染的关系

目的 探讨胃癌组织中hTERT、hMSH2基因在胃癌发生中的作用和Hp致癌的可能机制.方法 采用W-S法检测93例胃癌患者癌组织及癌旁组织中Hp感染情况;利用免疫组织化学方法检测93例胃癌患者癌组织及癌旁组织中hTERT、hMSH2的表达情况.结果 (1)胃癌组织hTERT阳性率为79.6%,明显高于癌旁组织22.6%(P＜0.01);Hp感染组hTERT蛋白表达阳性率高于非感染组(P＜0.01);(2)胃癌组织hMSH2阳性率为65.6%,明显高于癌旁组织38.7%(P＜0.01);Hp感染组hMSH2基因蛋白表达阳性率低于非感染组(P＜0.05).结论 Hp诱导的端粒酶的表达增高和错配修复基因hMSH2 的表达异常可能与胃癌的发生有关.     

肝外胆管癌及癌旁胆管组织中hTERT蛋白表达和临床病理学联系

端粒酶激活是肿瘤发生的重要事件，85％以上的人类肿瘤细胞或组织可表达端粒酶活性。端粒酶活性又是由端粒酶逆转录酶(hTERT)调节的，后者又是端粒酶活性的限速决定因素，其表达与端粒酶活性相关。关于福尔马林固定-石蜡包埋胆管癌组织中hTERT蛋白和基因表达的研究甚少。本文对收集的肝外胆管癌以及癌旁胆     

胃粘膜病变中人端粒酶催化亚单位、c—myc蛋白的表达及其相互关系

目的探讨胃粘膜病变中人端粒酶催化亚单位（human telomerase catalytic subunit，hTERT）的表达状况及其与c—myc蛋白表达的关系。方法应用免疫组织化学技术检测45例慢性胃炎和19例胃癌中hTERT和c—myc蛋白的表达。结果hTERT蛋白的表达率在胃癌组织中显著高于不典型增生、肠化生和萎缩性胃炎组织（P〈0．05）；在不典型增生组织中显著高于肠化生和萎缩性胃炎组织（P〈0．05）；在肠化生组织中显著高于萎缩性胃炎组织（P〈0．05）。c—myc蛋白的表达率在胃癌组织中显著高于不典型增生、肠化生和萎缩性胃炎组织（P〈0．05）；在不典型增生组织中显著高于肠化生和萎缩性胃炎组织（P〈0．05）；在肠化生组织中显著高于萎缩性胃炎组织（P〈0．05）。hTERT蛋白表达率在c—myc蛋白阳性患者中显著高于c-myc蛋白阴性患者（P〈0．01）。结论在胃癌和胃癌前病变阶段，端粒酶（telomerase）与c—myc均可能发挥重要作用，促进了胃癌的发生、发展;c-myc表达增加可能是胃粘膜上皮细胞端粒酶激活的主要机制之一。     

反义人端粒酶逆转录酶基因转染对人胃癌细胞系的影响

目的探讨反义人端粒酶(hTERT)基因治疗的可行性。方法构建hTERT基因的反义表达载体,经脂质体介导转染人未分化胃癌细胞系HGC-27,通过Southernblot检测外源反义基因的整合;RT-PCR及DNA测序法检测反义基因的转录;RT-PCR半定量方法检测被封闭目的基因mRNA的转录水平;TRAP及PCRELISA方法检测细胞的端粒酶活性;流式细胞仪检测细胞周期变化。结果外源反义hTERT基因已整合入细胞并获稳定转录,且能显著封闭目的基因转录的mRNA,并显著抑制HGC-27细胞的端粒酶活性,抑制HGC-27细胞的增殖并促进其凋亡。结论端粒酶反义hTERT基因可有效地应用于胃癌的基因治疗。     

茉莉酸甲酯诱导人肝癌细胞HepG2细胞凋亡过程中端粒酶活性变化

目的:探讨在茉莉酸甲酯(MeJA)诱导HepG2细胞凋亡过程中的端粒酶活性变化.方法:RT-PCR检测HepG2细胞中hTERTmRNA表达,免疫细胞化学检测 HepG2细胞端粒酶蛋白表达.结果:MeJA作用HepG2细胞48h后,hTE RTmRNA表达水平明显下降(P＜0.05);端粒酶蛋白表达水平明显降低(P＜0.01).结论:MeJA通过下调hTERT mRNA及其蛋白的表达,引起HepG2细胞凋亡,从而发挥抗肝癌作用.     

大肠癌与端粒酶活性相关性的研究

目的　探讨端粒酶活性在大肠癌发生、发展以及浸润转移中的意义。方法　应用端粒重复扩增 (TRAP)及免疫组织化学法对 30例大肠癌、癌旁组织、正常大肠组织及 2 0例大肠腺瘤性息肉组织端粒酶活性、端粒酶催化亚基蛋白 (hTERT)的表达进行检测。结果　端粒酶活性在癌组织中检出率明显高于其他组织 (P <0 .0 5) ;大肠癌组织端粒酶活性与淋巴结是否有转移之间关系密切 ,伴淋巴结转移大肠癌端粒酶阳性表达率明显高于无淋巴结转移者 (P <0 .0 5)。结论　端粒酶活性与大肠癌的发生发展以及浸润转移密切相关 ,检测端粒酶活性对临床预测大肠癌淋巴结转移趋势、评价恶性程度和判断预后均有重要意义     

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.