FAK对增生性瘢痕成纤维细胞中信号转导因子表达的影响

目的了解FAKSiRNA对于体外培养的增生性瘢痕成纤维细胞中与瘢痕增生相关因子整合素α1、TGF-βR、黏着斑激酶（Focalad hesivekinase，FAK）及α平滑肌肌动蛋白（α-smooth muscle actin，α—SMA）表达的影响，探索治疗增生性瘢痕的基因治疗方法。方法设计特异性探针合成FAKSiRNA片段，脂质体法转染体外培养的增生性瘢痕成纤维细胞，并用荧光定量PCR法（FO—PCR）检测、比较转染前后成纤维细胞内以上各因子的mRNA表达量的变化。结果转染48h后，FAK mRNA、整合素α1 mRNA、TGF—BR mRNA、α-SMA mRNA的表达明显下降（P〈0．05）。结论FAK SiRNA可能通过抑制增生性瘢痕成纤维细胞中整合素α1、TGF—βR、FAK和α-SMA的表达，从而抑制瘢痕的增生与挛缩。     

17—β雌二醇、孕酮对增生性瘢痕成纤维细胞转化生长因子—β1合成的影响

目的 研究雌激素、孕激素对增生性瘢痕形成的影响。方法 体外培养增生性瘢痕成纤维细胞（HSFB）,利用免疫组化及计算机图像分析系统测定转化生长因子（TGF－β1）含量。结果 较对照组,17－β雌二醇（17－βE2）各组的HSFB胞浆内阳性信号明显加强（P＜0．05）;而孕酮（P）各组均不明显（P＞0．05）。结论 在体外,17－βE2可以明显促进增生性瘢痕成纤维细胞的TGF－β1合成,而P的作用不明显。     

瘢痕疙瘩成纤维细胞中转化生长因子 -βⅠ、Ⅱ型受体的表达及调控

目的：了解瘢痕疙瘩成纤维细胞中转化生长因子(Transforming growth factor,TGF)－βⅠ、Ⅱ型受体的表达及TGF－β1,β3对其的影响。方法；体外培养瘢痕疙瘩成纤维细胞（KFB）和正常皮肤成纤维细胞（NFB），利用免疫组化及计算机图像分析系统测定TGF-βⅠ、Ⅱ型受体含量。结果：KFB胞浆内阳性信号明显强于NFB（P＜0．05）；经TGF－β1,β3处理组胞浆内阳性信号差别均不明显（P＞0．05）。结论：KFB存在高表达的TGF－βⅠ、Ⅱ型受体；TGF－β1,β3均能促进KFB TGF－βⅠ、Ⅱ型受体的表达。     

阻断转化生长因子-β受体信号转导降低瘢痕疙瘩细胞转化生长因子-β1自分泌的研究

目的 研究瘢痕疙瘩成纤维细胞转化生长因子－β1（TGF－β1）的自分泌现象和阻断TGF－β受体信号转导对TGF－β1自分泌的调控。方法 组织块法体外培养瘢痕疾疙瘩成纤维细胞，加入重组人源（rh）TGF－β1（5mg/L）或含缩短型TGF－βⅡ型体的重组腺病毒（50pfu/cell），并用Northern印迹观察它们对TGF－β1极其Ⅰ、Ⅱ型受体的基因调控。结果 rhTGF－β1能上调TGF－β1（30％－50％）和Ⅰ型受体（30％－90％）的基因表达，但不影响Ⅱ型受体的基因表达。短型TGF－βⅡ型受体在瘢痕疙瘩细胞的过度表达减少细胞TGF－β1（50％－65％）和Ⅰ型受体（21％－55％）的基因表达，但不影响Ⅱ型受体的基因表达。结论 瘢痕疙瘩细胞存在TGF－β1的自分泌现象，而缩短型TGF－βⅡ型受体的过度表达可以通过阻断TGF－β的信号转导来降低TGF－β1的自分泌。     

TGF-β和α-SMA在瘢痕组织中的表达及相关性研究

目的 检测转化生长因子－β（ＴＧＦ－β１,ＴＧＦ－β２,ＴＧＦ－β３）在增生性瘢痕和表浅性瘢痕中的表达,探讨其对增生性瘢痕的形成及α－平滑肌肌动蛋白（α－ＳＭＡ表达的可能作用。方法 采用免疫组化法检测２８例增生性瘢痕,１９例表浅性瘢痕和１６例正常皮肤组织中ＴＧＦ－β和α－ＳＭＡ的表达水平,并按年龄,性别,病程分组进行比较及ＴＧＦ－β和α－ＳＭＡ相关性分析。     

良性胆管狭窄形成机制的实验研究

目的：探讨良性胆管狭窄形成机制。方法：通过制作犬胆管损伤修复模型,术后采用免疫组化SP法法对巨噬细胞（MΦ）、TGF－β1及α－SMA在胆管愈合过程不同时期组织中的表达和分布进行研究。结果：MΦ、TGF－β1及α－SMA愈合过程中表达较强,且持续较长时间。MΦ阳性表达于粘膜固有层;TGF－β1主要表达于肉芽组织、成纤维细胞、MΦ及血管内皮细胞。α－SMA表达于肌纤维细胞胞浆。结论：MΦ、TGF－β1及α－SMA高表达是造成胆道愈合过程成纤维细胞增殖旺盛、细胞外基质过度沉积、胆道瘢痕性挛缩的重要因素。     

增生性瘢痕中TGF—β受体表达的研究

目的：了解TGF－β受体在增生性瘢痕中的表达，进一步认识TGF－β及其受体在增生性瘢痕形成过程中的作用。方法：应用免疫组化技术对正常皮肤用增生性瘢痕中I型和Ⅱ型TGF-β受体染色，并用图像分析系统进行半定量分析。结果：增生性瘢痕Fb中能检测到I型和Ⅱ型受体，而且随着病程的延长，受体表达逐渐减弱，直至消失；正常皮肤Fb未见受体表达阳性者。结论：①在增生性瘢痕形成过程中，不仅TGF－β增高，Fb表面I型和Ⅱ型TGF－β受体也增高，使TGF－β作用放大；②增生性瘢痕和瘢痕疙瘩中Fb出现表型变异，而且Fb表型随病程发生变化。     

粘着斑激酶在增生性瘢痕成纤维细胞中的表达和意义

目的探讨粘着斑激酶（FAK）在增生性瘢痕成纤维细胞（HSFB）中的表达和意义。方法运用细胞免疫组化技术，测定HSFB和正常皮肤成纤维细胞（NSFB）中的FAK、整合素α1、转化生长因子受体1（TGF-βR1）及α肌动蛋白（α—SMA）的表达；同时将HSFB分别用抗FAK、整合素α1、TGF-βR1及α—SMA抗体进行阻断培养，并测定培养前后整合素α1、TGF—βR1、α—SMA及FAK的表达。结果与NSFB相比，HSFB中的FAK、整合素α1、TGF—βR1、α—SMA的表达增高，差异具有显著意义（P〈0．05）。分别用抗整合素α1、TGF-βR1、α—SMA抗体进行阻断培养后，HSFB中的FAK表达下降（P〈0．01）；阻断FAK表达也可分别导致了整合素α1、TGF-βR1、α—SMA的表达降低（P〈0．01）。结论FAK对整合素α1、TGF-βR1及α—SMA的蛋白合成具有重要的调控作用，与增生性瘢痕的发生、发展关系密切。减少FAK在成纤维细胞中的过度表达，可能是抑制瘢痕增生、软化瘢痕的新途径。     

磷酸化Smad2和Smad7在增生性瘢痕成纤维细胞中的表达

Smads蛋白家族是近年来发现的转化生长因子（TGF）-β1受体下游信号蛋白，也是目前公认的介导TGF-β1胞内反应的主要通路。笔通过检测体外培养的增生性瘢痕成纤维细胞（HSF）和正常皮肤成纤维细胞（NSF）中磷酸化Smad2和抑制性信号介导子Smad7的表达差异，拟探讨二在增生性瘢痕发病机制中的作用。     

高压氧对兔耳增生性瘢痕形成的影响

目的：探讨高压氧（Hyperbaric oxygenation,HBO）对兔耳增生性瘢痕形成及对血管内皮生长因子（VEGF）、转化生长因子β1（TGFβ1）表达的影响。方法：选取20只新西兰大白兔建立兔耳瘢痕模型,每耳6个创面,随机分成实验组和对照组2组,每组10只,共120个创面,实验组术后立即给予HBO处理,对照组处于常压环境中。术后第29天切取瘢痕组织,测量瘢痕增生指数（hypertrophic index,HI）,并用HE染色观察瘢痕形态学变化,免疫组织化学方法检测TGFβ1及VEGF的表达。结果：实验组HI值明显低于对照组（P〈0．01）;HE染色结果示实验组成纤维细胞数目较对照组明显减少（P〈0．01）;免疫组织化学检测结果示实验组VEGF、TGFβ1的表达量较对照组显著降低（P〈0．01）。结论：HBO可降低VEGF、TGFβ1的表达,对兔耳增生性瘢痕有明显抑制作用。     

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.     

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.