早期生长反应基因-1参与学习记忆过程的研究进展

背景早期生长反应基因-1(the early growth response gene-1,Egr-1)参与长时程增强、促进神经元发生过程,其蛋白表达与突触可塑性及长期记忆的巩固、再巩固和消除密切相关.目的 以Egr-1基因的表达变化为切入点,为术后认知功能障碍的发生机制及防治手段提供更多研究靶点.内容全面阐述Egr-1的结构特点、分布、表达及其对学习记忆不同阶段的影响.趋向Egr-1基因在学习记忆的不同阶段发挥不同作用,但具体的分子信号通路及其在术后认知功能障碍中的作用尚有待进一步研究.     

α1-抗糜蛋白酶在认知功能中的作用

背景 认知功能障碍相关疾病如阿尔茨海默病(alzheimer's disease,AD)等发病率不断增多.研究表明α1-抗糜蛋白酶( alphal -antichymotrypsin,ACT),其过度表达在认知功能障碍中起着特殊作用.目的 分析总结ACT与认知功能障碍的相关性及其机制.内容 描述ACT在认知功能中的病理生理、遗传机制及作用.趋向 血浆中的ACT水平与认知恶化水平有关,但其在认知功能中的预警作用有待于进一步的研究.     

孕激素与认知功能及阿尔茨海默病关系研究进展

背景 内源性孕激素黄体酮不但是性激素,也是神经类固醇激素的一种,对神经发育、修复及相关疾病[如阿尔茨海默病(alzheimer's diseage,AD)]有重要影响.而越来越多的合成孕激素对神经系统的影响也渐受到研究人员的关注.目的 综述近年来孕激素与AD及认知功能关系相关文献,并阐释其可能机制,为研究合成的孕激素提供思路.内容 大量文献数据提示,黄体酮对AD发生发展及认知功能有积极作用,而合成的孕激素乙酸甲氧基孕酮则不然.现从细胞、动物实验及临床研究3个层面,从分子水平和功能研究,从学习记忆基础和AD发病成因等方面阐述其可能机制.趋向 越来越多的合成孕激素应用于临床,它们对AD发病和认知功能的影响有待于进一步阐明.     

基底外侧杏仁核-上边缘皮质BDNF在小鼠围术期神经认知紊乱中的作用：与TrkB受体的关系

目的评价基底外侧杏仁核(BLA)-上边缘皮质(PL)脑源性神经营养因子(BDNF)在小鼠围术期神经认知紊乱中的作用及其与酪氨酸激酶受体B(TrkB)受体的关系。方法清洁级健康C57BL/6J小鼠48只,6月龄,体重25～30 g,采用随机数字表法分为4组(n=12):对照组(C组)、手术组(S组)、BLA区BDNF过表达组(B组)和BLA区BDNF过表达+PL区注射ANA-12组(A组)。S组于条件恐惧记忆实验训练期结束后30 min时行腹部探查术;B组在BLA区注射重组腺病毒0.3 μl,3周后进行条件恐惧记忆实验,于训练期结束后30 min时行腹部探查术;A组在BLA区域注射重组腺病毒0.3 μl,并在PL区置管,3周后进行条件恐惧记忆实验,于训练期开始前30 min时,经PL套管注射TrkB受体拮抗剂ANA-12 0.25 μg,于训练期结束后30 min行腹部探查术。均于条件恐惧记忆实验训练期结束后24 h开始测试期,计算僵直时间百分比。行为学测试结束后30 min,采用免疫印迹法检测脑区BDNF、磷酸化TrkB(p-TrkB)和磷酸化细胞外调节蛋白激酶(p-ERK1/2)的表...     

孕激素与认知功能及阿尔茨海默病关系研究进展

背景 内源性孕激素黄体酮不但是性激素,也是神经类固醇激素的一种,对神经发育、修复及相关疾病[如阿尔茨海默病(alzheimer's diseage,AD)]有重要影响.而越来越多的合成孕激素对神经系统的影响也渐受到研究人员的关注.目的 综述近年来孕激素与AD及认知功能关系相关文献,并阐释其可能机制,为研究合成的孕激素提供思路.内容 大量文献数据提示,黄体酮对AD发生发展及认知功能有积极作用,而合成的孕激素乙酸甲氧基孕酮则不然.现从细胞、动物实验及临床研究3个层面,从分子水平和功能研究,从学习记忆基础和AD发病成因等方面阐述其可能机制.趋向 越来越多的合成孕激素应用于临床,它们对AD发病和认知功能的影响有待于进一步阐明.

Abstract：

Background Endogenous progestin, progesterone, is not only a gonadal hormone, but also one of the neurosteroids, which exerts profound effects on neurogenesis, repair and central nervous system related diseases, such as Alzheimer's disease (AD). As more and more synthetic progestins are being introduced into clinical application, their effects on nervous system are attracting researchers' concern. Purpose Recent literature on the relationship between progestins and Alzheimer's disease or cognitive function was reviewed to provide some mechanism-based ideas for further research on artificial progestins. Content A great amount of literature suggested that progesterone had beneficial effects on AD and cognitive function, while the synthetic progestin methoxyprogesterone acetate (MPA) had adverse effects. The possible mechanisms are elucidated in this review based upon the results of cell culture, animal experiment and clinic research, from different aspects of molecular mechanism, functional research, basis oflearning and memory and pathogenesis of AD. Trend More and more artificial progestins are being used in the clinic, however, their impacts on AD development and cognitive functions still need to be further expounded.     

术后认知功能障碍治疗的新靶向-γ-氨基丁酸A型受体相关药物

背景 术后认知功能障碍(postoperative cognitive dysfunction,POCD)是一种常见的围术期并发症.γ-氨基丁酸A型(γ-aminobutyricacid type A,GABAA)受体作为一种中枢神经抑制性受体,可能对POCD的发生起着关键性作用.目的 综述以GABAA受体为靶点的相关药物对POCD的影响.内容 与GABAA受体相关的3类药物:激动剂、拮抗剂和反向激动剂,对POCD可分别产生诱发、逆转和改善症状的作用. 趋向 对记忆或者认知功能损害具有改善作用的GABAA受体相关药物,对POCD的治疗具有重大意义,将成为今后POCD的研究热点.     

高压氧处理对患者术后认知功能障碍的影响

背景 术后认知功能障碍(postoperative cognitive dysfunction,POCD)指的是患者手术麻醉后出现的认知功能减退,往往产生长久的严重后果,尤其是老年患者.高压氧(hyperbaric oxygen,HBO)处理作为一项辅助治疗措施目前已广泛应用于临床,大量研究证实HBO处理对大脑、心脏及肝等多种器官具有保护作用.已有研究者将HBO处理运用到认知功能障碍的研究中. 目的 探讨HBO处理对患者POCD的影响及其作用机制,为改善老年患者手术后认知功能及长期预后提供有效措施. 内容 对HBO处理、HBO处理用于POCD的研究情况及HBO改善POCD的作用机制进行综述. 趋向 HBO处理是近年来用于多脏器保护的重要措施,其脑保护作用为临床预防及改善POCD提供了新的思路.     

生长抑素中间神经元与认知功能关系的研究进展

神经网络是学习与记忆等认知功能的生物学基础,而兴奋与抑制功能失衡很可能是神经精神疾病发生的重要病理机制。其中,γ-氨基丁酸(GABA)能抑制性中间神经元及其抑制性神经环路在神经网络形成中起重要调节作用。越来越多的研究表明,生长抑素(somatostatin,SOM)中间神经元参与调控神经网络活动并在认知功能中发挥关键作用。本文主要就SOM中间神经元在认知功能及相关疾病中的作用作一综述,以期为认知功能相关的研究提供参考。     

记忆巩固研究的新进展

记忆包括记忆的编码、巩固和检索3个过程, 其为大脑重要的高级神经功能之一。记忆巩固是指记忆的内部表征及其神经生物学随时间而变化的过程, 其本质是在神经元、脑区或脑亚区之间形成新的稳定联系。记忆巩固在编码后立即开始, 可能会持续若干天, 甚至若干年。文章综述了记忆巩固在清醒和睡眠两种大脑状态的整个过程及记忆巩固神经加工机制等方面的研究进展, 以期阐明记忆巩固现象的相关生物学机制。     

Toll样受体4在小胶质细胞炎症反应中的作用与认知功能的关系

概述 小胶质细胞在术后早期中枢炎症反应中担当主角.而Toll样受体4(toll-like receptor 4,TLR4)在小胶质细胞的活化与炎症反应中发挥着不可或缺的作用.中枢炎症细胞因子可通过多种途径影响中枢有关受体或递质功能,从而影响学习记忆和认知能力. 目的 探讨TLR4在小胶质细胞炎症反应中作用及与认知功能的关系. 内容 主要从4个方面进行综述:TLR4与小胶质细胞的关系、小胶质细胞与中枢炎症的关系、炎症和TLR4对认知的影响. 趋向 小胶质细胞在中枢神经系统(central nervous system,CNS)的炎症反应中担当主角.TLR4在小胶质细胞的激活中起关键作用,但TLR4在小胶质细胞相关的中枢炎症反应和认知中的作用尚不清楚.     

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.