胶质细胞源性神经营养因子与脊髓损伤治疗

脊髓损伤治疗是医学界的热点和难点,从传统的大剂量激素冲击、手术解除压迫、术后康复锻炼等到干细胞移植、基因疗法等均未取得满意效果.大量研究证实,胶质细胞源性神经营养因子(GDNF)有促进脊髓损伤修复的作用,为脊髓损伤治疗带来新方法.该文就GDNF结构特性及在脊髓损伤修复中的作用研究进展作一综述.     

胚胎干细胞移植治疗脊髓损伤的研究进展

脊髓损伤是中枢神经系统的严重创伤,常导致不可逆的感觉及运动功能丧失,主要表现为损伤平面以下感觉、运动功能丧失和大小便功能障碍,并由此引起的一系列并发症(褥疮、坠积性肺炎、尿路感染等).目前,细胞移植治疗脊髓损伤实验取得了一定的进展,为严重脊髓损伤的治疗提供r新的方法.细胞移植根据移植物的不同可以大体分为神经细胞移植和非神经细胞移植,移植物包括胚胎干细胞(embryonic stem cell,ESC)、嗅鞘细胞、活化巨噬细胞、骨髓基质干细胞等.其中胚胎干细胞移植治疗已是脊髓损伤的研究热点之一.     

骨髓间充质干细胞移植治疗脊髓损伤研究

20世纪90年代成功分离出骨髓间充质干细胞(BMSC)并移植用于治疗急性脊髓损伤动物模型,引起了广泛关注。BMSC移植治疗脊髓损伤的实验研究主要有单独移植、联合支架移植、联合细胞移植、联合药物移植及转基因干细胞移植等。该文就BMSC生物学特性、BMSC移植治疗脊髓损伤研究现状及进展作一简要综述。     

干细胞移植治疗脊髓损伤后排尿障碍的可行性

一直以来,脊髓损伤因其高致残率而被视为医学界的一大难题。在脊髓损伤的诸多并发症中,泌尿系统并发症是脊髓损伤患者最主要的死因之一。由于损伤的神经细胞无法再生,目前对于脊髓损伤患者排尿障碍的各种治疗效果都十分有限。然而,随着干细胞研究的不断进展,越来越多的实验表明干细胞移植治疗可以改善脊髓损伤后的排尿功能,提示该方法具有一定的可行性。本文就近年来关于干细胞移植治疗脊髓损伤后排尿障碍的研究进展,从常用干细胞种类、干细胞移植治疗的机制、干细胞移植时间、干细胞移植途径几个方面做一综述,并提出通过干细胞体外分化得到能够分泌5-羟色胺的神经细胞来进行移植治疗脊髓损伤后排尿障碍的新思路。     

胶质细胞源性神经营养因子与脊髓损伤治疗

脊髓损伤治疗是医学界的热点和难点,从传统的大剂量激素冲击、手术解除压迫、术后康复锻炼等到干细胞移植、基因疗法等均未取得满意效果。大量研究证实,胶质细胞源性神经营养因子(GDNF)有促进脊髓损伤修复的作用,为脊髓损伤治疗带来新方法。该文就GDNF结构特性及在脊髓损伤修复中的作用研究进展作一综述。     

神经干细胞与脊髓损伤修复实验研究进展

脊髓损伤治疗仍是一个世界性的难题,临床常用的药物治疗、手术减压等效果均不够理想.近年来神经干细胞的发现及成功分离培养,使人们看到了治疗中枢神经系统损伤的新希望.神经干细胞修复脊髓损伤的动物实验研究主要集中在两个方面,一是神经干细胞的直接移植,但是许多实验结果显示移植的神经干细胞很少转化为神经元和少突胶质细胞,大部分转化为星形胶质细胞,其主要与损伤部位的微环境有关;二是携带有外源基因的神经干细胞转基因治疗,由于所携带的外源基因具有部分调控损伤部位微环境的神经因子,提高了神经干细胞向神经元和少突胶质细胞分化的能力,成为近年来实验研究的热点.该文就神经干细胞与脊髓损伤修复的近年实验研究及其发展动态作一综述.     

干细胞修复脊髓损伤的研究现状及应用前景

目的 综述有关干细胞移植治疗脊髓损伤(spinal cord injury,SCI)的现状及前景.方法 广泛查阅近年国内外相关文献,对干细胞生物学特性、移植治疗SCI的实验研究、治疗机制和存在的问题进行讨论和分析.结果 基础实验和临床研究表明,干细胞治疗SCI研究已有很大进展,它可以在脊髓内迁移、分化为神经元以及分泌神经营养物质,具有促进SCI后神经功能恢复的作用,但也存在很多问题.结论 干细胞治疗SCI是一种有前景的治疗方法,但尚有很多问题亟待解决.     

不同移植时间对胚胎脊髓源性神经干细胞体内分化为神经元影响的实验研究

目的 探讨不同移植时间对胚胎脊髓源性神经干细胞体内分化为神经元影响,为胚胎脊髓源性神经干细胞移植防治骨骼肌失神经萎缩的最佳移植时间点的选择提供实验依据.方法 从孕龄14 d SD大鼠胚胎脊髓组织中分离、获得并鉴定脊髓源性神经干细胞.90只SD大鼠分为9组,分别于胫神经切断后0、1、2、3、4、6、8、12及16周,移植胚胎脊髓源性神经干细胞至切断胫神经远端神经外膜下,移植后4周取胫神经冰冻切片行免疫组化方法 计数神经元数量并进行图像分析.结果 损伤后1周移植时,神经元数量最多,其次为损伤后6周,损伤后16周组无神经元存在.结论 对胚胎脊髓源性神经干细胞体内移植后分化为神经元影响最小的时间点是损伤后1周,因此我们可以推断胚胎脊髓源性神经干细胞移植防治骨骼肌失神经萎缩的最佳移植时间点是损伤后1周.     

神经干细胞移植治疗脊髓损伤的研究进展

脊髓损伤(spinal cord injury,SCI)是一种严重的中枢神经系统创伤性疾病,可导致患者终生残疾,甚至引起死亡。药物、手术等治疗方式无法从根本上改善脊髓损伤患者神经功能。神经干细胞(neural stem cells,NSCs)具有自我更新和多向分化潜能,移植后可通过补充、替代神经元,分泌神经营养因子,改善局部免疫环境等机制促进脊髓功能恢复,为修复脊髓损伤带来了希望。研究者利用转基因的手段将神经营养因子等导入到拟移植的神经干细胞,或通过联合其他类型细胞、支架材料等方法进一步提高移植效率和治疗效果。尽管神经干细胞移植已经取得了很大进展,还有很多问题尚待解决,如移植治疗的具体机制、移植细胞的存活和分化、伦理学争议、免疫排斥和致瘤性等。本文拟对NSCs的生物学特征、移植治疗的机制和不同移植方式进行综述,并对NSCs移植治疗SCI的应用前景与存在问题进行展望。     

自体骨髓干细胞移植治疗脊髓损伤神经源性膀胱疗效观察:1例脊髓损伤患者移植前后尿动力学指标变化

目的 探讨自体骨髓干细胞移植治疗脊髓损伤患者神经源性膀胱的效果.方法 脊髓损伤患者1例,于伤后13 d开始给予规律自体骨髓干细胞移植治疗,共9次,检测治疗前后尿动力学指标.结果 患者伤后26 d最大尿道压及尿道闭合压力明显升高,膀胱容量增大;伤后140 d时患者膀胱感觉恢复,可诱发出逼尿肌自主收缩,最大压力为30 cm...     

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.     

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.     

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.