脊髓胶质细胞活化与病理性疼痛调节

背景 研究表明脊髓胶质细胞(星形胶质细胞和小胶质细胞)在各种病理性疼痛模型中活化,并且活化的胶质细胞在各种病理性疼痛的发生和发展中具有重要作用.目的 探讨脊髓胶质细胞在病理性疼痛调节中的作用.内容 从脊髓胶质细胞活化参与病理性疼痛调节的生理基础,脊髓胶质细胞活化及其检测,脊髓胶质细胞活化与病理性疼痛和脊髓胶质细胞参与病理性疼痛的调节机制等几方面就与此有关的研究进展进行了综述.趋向 胶质细胞将继续引起疼痛研究者的关注,因为它为临床病理性疼痛的治疗提供了新的靶点.     

脊髓胶质细胞活化与病理性疼痛调节

背景 研究表明脊髓胶质细胞(星形胶质细胞和小胶质细胞)在各种病理性疼痛模型中活化,并且活化的胶质细胞在各种病理性疼痛的发生和发展中具有重要作用.目的 探讨脊髓胶质细胞在病理性疼痛调节中的作用.内容 从脊髓胶质细胞活化参与病理性疼痛调节的生理基础,脊髓胶质细胞活化及其检测,脊髓胶质细胞活化与病理性疼痛和脊髓胶质细胞参与病...     

小胶质细胞与疼痛敏化调控

小胶质细胞激活后充当中枢神经系统的免疫效应细胞，活化的小胶质细胞是脑内细胞因子的重要来源和作用部位，参与疼痛敏感化的病理发生过程。研究证实，神经损伤后小胶质细胞是中枢神经系统中反应较早的胶质细胞，激活的小胶质细胞释放的一些生物活性物质，能导致星形胶质细胞的激活，反过来维持较持久的疼痛状态。本文就脊髓小胶质细胞在神经病理性疼痛中的变化及其分子机制和临床联系作一综述。     

高压氧后处理对大鼠神经病理性痛及脊髓小胶质细胞活化的影响

目的 探讨高压氧(hyperbaric oxygen,HBO)后处理对大鼠神经病理性疼痛(neuropathic pain,NP)镇痛效果及脊髓小胶质细胞活化的影响. 方法 雄性SD大鼠24只,采用随机数字表法将大鼠分成4组(每组6只):假手术组(S组)、坐骨神经慢性压迫组(C组)、HBO后处理2.0组(H2.0组)与HBO后处理2.5组(H2.5组).采用坐骨神经慢性压迫损伤法建立NP模型,H2.0和H2.5组于术后1d开始给予相应压力的HBO后处理,1次/d连续7次,每天出HBO舱后1h测定各组大鼠机械缩足反射阈值(mechanical withdrawal threshold,MWT)和热缩足反射潜伏期(thermal withdrawal latency,TWL),术后7d测定MWT和TWL后处死,用免疫组化法测定大鼠脊髓小胶质细胞的活化情况. 结果 与S组比较,C组MWT降低及TWL缩短,脊髓内小胶质细胞数量与活化率上升为(156±9)个和44.9％(P＜0.05);与C组比较,H2.0组和H2.5组MWT升高及TWL延长,H2.0组和小胶质细胞数量与活化率分别为(64±7)个和5.7％(P＜0.05),H2.5组小胶质细胞数量与活化率分别为(62±5)个和6.1％(P＜0.05);H2.0组与H2.5组小胶质细胞数量与活化率差异无统计学意义(P＞0.05). 结论 HBO后处理可减轻大鼠NP,其机制与抑制脊髓内小胶质细胞活化有关.     

抑制病理性疼痛相关胶质细胞活化药物的研究进展

背景 病理性疼痛的产生和持续机制十分复杂.近些年越来越多的研究者关注到脊髓胶质细胞在病理性疼痛中所发挥的作用,其中胶质细胞活化和增殖的抑制剂成为了研究的重点.目的 系统阐述胶质细胞在病理性疼痛中的作用和部分胶质细胞抑制剂的作用机制及研究进展.内容 胶质细胞不仅具有营养和支持作用,还参与了病理性疼痛,已有许多实验证实了应用胶质细胞抑制剂可以减弱胶质细胞的激活从而削弱疼痛反应.趋向 期望能为进一步的药物实验研究提供有价值的思路和借鉴.     

碱性成纤维细胞生长因子与慢性疼痛调控的研究进展

背景慢性、持续的疼痛可能是患者就医最常见的原因,因此,临床上对慢性疼痛的治疗日益重视.目的简要介绍碱性成纤维细胞生长因子(basic fibroblast growth factor,FGF-2)的生物学特性及功能,重点综述其与星形胶质细胞活化的关系及参与慢性疼痛调控的研究进展.内容星形胶质细胞在慢性疼痛的发生、发展过程中起着关键作用,FGF-2是星形胶质细胞的有效激活剂,慢性疼痛发生时FGF-2在活化的脊髓星形胶质细胞中增加.趋向FGF-2调控疼痛的信号转导通路有待进一步研究,疼痛过程是由多种细胞和因子共同调节,它们的相互作用机制有待于进一步探讨.     

脊髓G蛋白耦联受体激酶2在神经病理性疼痛中作用的研究进展

背景 近年研究发现脊髓G蛋白耦联受体激酶2（Gprotein-coupled receptor kinase 2,GRK2）在神经病理性疼痛（neuropathic pain,NP）形成和维持中起到至关重要的作用.目的 对脊髓GRK2在NP中作用的研究有助于人们更清楚地理解NP产生和维持的相关分子机制,为NP的治疗提供新思路.内容 分别描述GRK2、脊髓GRK2与NP以及GRK2参与NP的可能机制.趋势 鉴于脊髓GRK2在NP中的重要作用,GRK2将有可能为针对NP发病机制的治疗提供新的靶点.     

交质细胞在慢性疼痛中的病理及保护作用

目前认为,胶质细胞在病理性疼痛和慢性疼痛的发病机制中起了重要作用。胶质细胞受到激活后,星形胶质细胞和小胶质细胞都会做出反应,释放许多的信号分子。这些信号分子,或者具有保护作用,或者具有病理效应。在此,简单综述了胶质细胞对病理性疼痛的病理机制和其对神经元保护作用的基础。胶质细胞抗炎作用的保护性机制,已被作为研究新型神经病理性疼痛药物的靶点。考虑到目前慢性疼痛的普遍性和目前药物疗效的有限性。在新的关于胶质细胞——神经元细胞相互关系的理论指导下．研究和制定新的疼痛控制策略是值得的。     

活化的小胶质细胞在中枢神经系统中的作用

小胶质细胞是中枢神经系统一种重要的免疫细胞,在很多中枢神经系统疾病中．小胶质细胞可发生活化．活化的小胶质细胞可发生增殖,迁移,分泌可溶性因子和电生理改变等变化．内源性大麻素系统可对活化的小胶质细胞产生重要调控作用．因此,活化的小胶质细胞在中枢神经系统中起重要作用.     

脊髓胶质细胞的激活及其信号传递

正常情况下脊髓胶质细胞对疼痛不产生任何影响.但激活的胶质细胞及其释放的促炎症物质,特别是促炎症细胞因子有增强疼痛效应.然而胶质细胞如何被激活是一个关键问题,神经元-胶质细胞间信号分子可能在这方面具有重要作用.     

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.     

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.     

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.     

Intraoperative autotransfusion is associated with modest reduction of allogeneic transfusion in prosthetic hip surgery

Background: The efficacy of intraoperative salvage and washing of wound blood and the predictors of allogeneic red cell transfusions in prosthetic hip surgery are insufficiently known.
Methods: In 96 patients, undergoing primary or revision surgery, salvaged and washed red cells and, if necessary, allogeneic blood were used to keep haematocrit not lower than 33%. The bleeding of red cells during hospital stay was calculated from the red cell balance. The preoperative red cell reserve (millilitres of red cells in excess of a haematocrit of 33%) was estimated and the difference between this volume and the total bleeding of red cells was retrospectively used to classify patients with regard to the need for red cells. Stepwise regression analysis was used to define patient-related variables associated with allogeneic blood transfusion.
Results: Preoperative knowledge of the type of operation (primary, revision), the preoperative red cell reserve, and the body mass could predict roughly half of the need for banked blood (r²=0.45). Only one-third of the total bleeding of red cells was retransfused. For complete avoidance of allogeneic blood, autotransfusion was most effective in patients with a moderate need (0–4 u). However, 32% of such patients required allogeneic blood.
Conclusions: Autotransfusion has a limited efficacy to decrease the need for allogeneic blood, and other blood-saving methods should be added for this purpose. It is difficult to predict the need for allogeneic blood preoperatively.     

缺氧对肾小管上皮细胞分泌外泌体的影响

目的    观察缺氧对肾小管上皮细胞分泌外泌体的影响,探讨外泌体在缺氧致肾脏损伤中的作用及机制。 方法    （1）常氧（21% O₂）及缺氧（1% O₂）分别处理大鼠肾小管上皮细胞（NRK-52E）48 h,收集细胞上清液并使用高速梯度离心法分离外泌体。采用透射电镜、纳米示踪分析、Western印迹、蛋白浓度定量鉴定并比较两组外泌体的基本特性。（2）在共培养实验中,以不同浓度（1、10、50、100、300 mg/L）的常氧外泌体、缺氧外泌体分别干预脂多糖（LPS）诱导的大鼠原代腹腔巨噬细胞,使用实时荧光定量PCR与酶联免疫吸附试验（ELISA）法分别检测巨噬细胞白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）、诱导型氮氧化物合酶（iNOS）水平;使用Western印迹法检测巨噬细胞磷酸化（p）STAT/STAT及细胞因子信号传导抑制蛋白1（SOCS1）的蛋白表达;最后,使用实时荧光定量PCR法检测常氧外泌体与缺氧外泌体中炎性反应相关微RNA（microRNA,miR）的表达差异。 结果    （1）离心得到的囊泡具有外泌体典型的结构,粒径小于150 nm,表达外泌体标志蛋白CD63,说明分离得到外泌体。缺氧对肾小管上皮细胞分泌的外泌体形态、粒径分布比例无明显影响,但提高了外泌体的分泌量。（2）缺氧外泌体相比于常氧外泌体促进了LPS诱导的M1型巨噬细胞IL-6、TNF-α、iNOS 的表达和分泌（均P＜0.01）,同时提高STAT的磷酸化水平并减少SOCS1的蛋白表达（均P＜0.01）;对炎性反应相关microRNA检测发现缺氧外泌体中miR-155、miR-27a表达量较常氧外泌体明显升高（P＜0.05）。 结论    缺氧可改变外泌体的生物学功能,表现为协同促进LPS诱导的M1型巨噬细胞的表型转化,这可能是慢性肾脏病微炎性反应状态持续的原因之一。     

In Vitro Function and Durability Assessment of a Novel Polyurethane Heart Valve Prosthesis

Abstract While flexible-leaflet, central-flow prosthetic heart valves promise relief from anticoagulation therapy, they continue to be restricted by inadequate durability. In consequence, a novel trileaflet valve, made entirely from polyurethane, has been developed. A batch of 6 consecutively manufactured polyurethane valves was subjected to hydrodynamic function and accelerated fatigue testing. Computerized data acquisition and control systems have been introduced to improve valve testing methodologies. In terms of hydrodynamic function, the polyurethane valve demonstrates transvalvular pressure gradients similar to those for a bioprosthetic valve (Carpentier-Edwards) and levels of retrograde flow significantly less than those for either the bioprosthetic valve or a bileaflet mechanical valve (St Jude Medical). The equivalent of 10 years of cycling without failure has been exceeded by all 6 polyurethane valves in accelerated fatigue tests with 2 valves remaining intact after 674 million cycles (equivalent to approximately 17 years) in continuing tests. Highspeed photography revealed considerable differences in leaflet motion between valves cycled at accelerated and physiological rates.     

Negative pressure ventilation vs. spontaneous assisted ventilation during rigid bronchoscopy: A controlled randomised trial

Background: Ventilation during interventional rigid bronchoscopy (IRB) under general anaesthesia (jet ventilation, positive pressure ventilation and spontaneous assisted ventilation) may offer some difficulties. This study compares the effectiveness during IRB of intermittent negative pressure ventilation (INPV) and spontaneous assisted ventilation (SAV). Methods: Thirty-eight patients submitted to IRB were randomised into two groups: SAV or INPV. All patients received a total intravenous anaesthesia; INPV patients were paralysed. Pre-and intra-operative arterial blood gases and O₂ flow through a rigid bronchoscope were assessed. The endoscopist applying a subjective score evaluated the operating conditions. Results: Patients of the INPV group, as compared to the SAV group, required a lower dosage of fentanyl (2.6 ± 1.8 (μg · kg^?1· h^?1 vs. 6.6 ± 4.8 μg · kg^?1· h^?1), a lower O₂ supply (3.3 ± 2.8 1/min vs. 11.6 ± 3.4 1/min), a shorter recovery time (5.4 ± 2.9 min vs. 9.8 ± 7.1 min) and no manually assisted ventilation (0 ± 0 vs. 1 ± 1.1 nd?/procedure). Intraoperative PaCO₂ was higher in the SAV (8.1 ± 1.3 kPa) than in the INPV group (5.0 ± 1.6 kPa) and intraoperative pH differed in the two groups (7.26 ± 0.05, SAV vs. 7.47 ± 0.08, INPV). Operating conditions, as assessed by a subjective score, were considered better with INPV than with SAV (4.9 vs. 4.3). Conclusions: As compared to SAV, INPV in paralysed patients during IRB reduces administration of opioids, shortens recovery time, prevents respiratory acidosis, excludes the need for manually assisted ventilation, reduces 02 need and affords optimal surgical conditions. INPV appears a safe, non-invasive and effective ventilatory management during IRB.