滥用氯胺酮致膀胱功能障碍患者膀胱组织中P2X3受体的表达及其临床意义

目的:研究P2X3受体在滥用氯胺酮致膀胱功能障碍患者膀胱组织中的表达及其临床意义,讨论P2X3受体在滥用氯胺酮致膀胱功能障碍中的作用。方法:采用免疫组织化学方法分别检测36例滥用氯胺酮致膀胱功能障碍患者(试验组)和36例正常患者(对照组)膀胱组织中P2X3、M2、M3受体的表达情况,利用全自动显微镜及图像分析系统对免疫组化染色结果进行图像采集分析,测量其平均灰度值,同时比较两组间P2X3、M2、M3受体表达的差异。结果:P2X3受体主要在膀胱黏膜移行上皮细胞表达,试验组P2X3受体表达明显增强,与对照组比较差异有统计学意义(P0.01);而M2、M3受体表达与对照组比较差异无统计学意义(P0.01)。结论:滥用氯胺酮致膀胱功能障碍患者膀胱组织中P2X3受体表达显著增强,而M2、M3受体并未异常表达,提示P2X3受体上调可能在滥用氯胺酮致膀胱功能障碍中发挥关键作用。     

女性膀胱过度活动症患者膀胱内P2X3受体的表达及其意义

目的:研究P2X3受体在女性膀胱过度活动症患者膀胱内的表达及其临床意义,讨论P2X3受体在膀胱过度活动症中的作用。方法:采用免疫组织化学SABC法分别检测21例女性膀胱过度活动症患者和9例正常膀胱组织中P2X3受体的表达情况,利用全自动显微镜及图像分析系统对免疫组化染色结果进行图像采集分析,测量其平均光密度值,同时比较两组间P2X3受体表达的差异。结果:P2X3受体表达主要位于膀胱黏膜及黏膜下层,实验组P2X3受体表达显著增强,平均光密度值为(0.491 20±0.038 48),正常组P2X3受体表达明显偏低,平均光密度值为(0.260 70±0.031 43),组间比较差异有统计学意义(P<0.05)。结论:女性膀胱过度活动症患者膀胱组织中P2X3受体的表达显著提高,提示P2X3受体与女性膀胱过度活动症的发病机制密切相关,膀胱感觉功能异常可能是导致女性膀胱过度活动症发生的主要病因之一。     

间质性膀胱炎大鼠动物模型膀胱黏膜保护前后组胺受体变化及意义

目的 探讨透明质酸膀胱灌注治疗间质性膀胱炎(IC)后膀胱组织中组胺受体变化的意义. 方法 IC模型大鼠20只,随机分为2组,每组10只.实验组尿道灌注0.8 g/L透明质酸.对照组即时处死.HE染色计数膀胱固有层单核炎症细胞,特殊染色计数肥大细胞.免疫组化染色2组大鼠膀胱组织,IPP4.5图像分析软件计算吸光度(A)值,比较2组间的差异. 结果 实验组单核炎症细胞数和肥大细胞数分别为(12.20±2.48)、(2.90±0.87)个/视野;组胺H1～H4受体A值分别为0.015±0.007、0.006±0.001、0.007±0.004、0.061±0.026;对照组单核炎症细胞数和肥大细胞数分别为(23.90±3.07)、(7.08±1.23)个/视野;组胺H1～H4受体A值分别为0.055±0.033、0.031±0.023、0.033±0.017、0.091±0.059.2组单核炎症细胞和肥大细胞数比较差异均有统计学意义(P＜0.01);H1、H2、H3受体A值明显减小(P＜0.05);组胺H4受体A值差异无统计学意义(P＞0.05). 结论 组胺H1、H2、H3受体参与IC发生,其受体拮抗剂可能用于临床治疗IC.     

间质性膀胱炎发生前后膀胱组织组胺受体变化的动物实验研究

目的 探讨大鼠间质性膀胱炎发生前后膀胱组织中4种组胺受体(H1R、H2R、H3R和H4R)表达的变化. 方法体质量250～300 g的雌性SD大鼠30只,随机分为实验组(20只)和对照组(10只).实验组采用硫酸鱼精蛋白加氯化钾经尿道膀胱灌注建立间质性膀胱炎动物模型,2个月后处死,对照组直接处死.切取2组大鼠膀胱组织后行免疫组化染色,利用IPP 4.5图像分析软件计算各组组胺受体平均吸光度(-A)值,并进行统计学比较. 结果4种组胺受体主要表达于膀胱黏膜层,实验组H1R的(-A)值为0.054±0.031、H2R为0.032±0.021、H3R为0.047±0.033、H4R为0.149±0.191,对照组分别为0.017±0.011、0.018±0.015、0.014±0.011、0.060±0.039.实验组H1R、H2R和H3R的(-A)值明显高于对照组(P＜0.05),H4R的(-A) 值与对照组比较差异无统计学意义(P＞0.05). 结论H1R、H2R和H3R在间质性膀胱炎大鼠膀胱黏膜中表达显著升高,可能与间质性膀胱炎的发生相关,H3R可能是治疗间质性膀胱炎的新靶点.     

P2X受体在膀胱中的研究进展

P2X受体是细胞外非选择性门控阳离子通道,细胞外ATP是其天然配体,目前研究发现P2X受体有7个亚型,即P2X1-P2X7,它们在膀胱上的表达和分布各不相同,与膀胱的收缩功能关系密切,当膀胱发生病理改变时,它们在膀胱上的表达和功能也会发生改变.特别是P2X1,P2X3受体亚型目前的研究提示它们可能是起作用的主要受体亚型.本文对这方面的研究进展作一综述.     

氯胺酮相关性膀胱功能障碍（附8例报告）

目的：探讨滥用氯胺酮所引起的膀胱功能障碍及诊治方法.方法：回顾分析8例有滥用氯胺酮病史患者的泌尿系症状,给予常规检查及泌尿系统相关检查,根据不同情况给予患者探讨性治疗.结果：氯胺酮相关性膀胱功能障碍是以尿频,尿急为主的下尿路症状,膀胱镜检示膀胱黏膜不同程度炎症变化,8例患者经治疗有5例患者病情有所减轻.结论：氯胺酮相关性的膀胱功能障碍发生机制、发展、转归、治疗都缺乏足够的认识,需要更进一步的研究. 关键词：膀胱功能障碍;氯胺酮;滥用 分类号：R694 文献标识码：A 文章编号：1001-1420（2011）01-0039-03     

糖尿病大鼠膀胱收缩功能改变与M3受体关系的实验研究

目的探讨糖尿病性膀胱发病机制中逼尿肌M3受体的改变情况。方法以链脲佐菌素诱导2型糖尿病大鼠成模。应用尿动力仪检测逼尿肌收缩功能；Westernblot、RT—PCR方法检测膀胱M3受体含量。结果病程2周时糖尿病组大鼠膀胱逼尿肌收缩力增加伴M3受体表达增强；病程4周时糖尿病组大鼠膀胱逼尿肌收缩力低于正常对照组，但尚无统计学意义；病程12周时糖尿病组大鼠膀胱逼尿肌收缩力降低伴M，受体表达减少。结论膀胱收缩功能和M3受体蛋白含量及M3受体mRNA的含量三者呈同向变化关系。在糖尿病大鼠发病早期三者均升高，但是随着病程进展却都降低了。这可能是早期糖尿病性膀胱病变的发病机制之一。     

隔姜灸对大鼠脊髓损伤后神经源性膀胱M2、M3乙酰胆碱mRNA及P2X3受体表达的影响

目的 探讨隔姜灸改善脊髓损伤大鼠神经源性膀胱症状的作用靶点,为脊髓损伤神经源性膀胱患者临床干预提供理论基础。 方法 选取SD大鼠为实验动物,随机分组后,按照改良Allen′s法建立T10脊髓损伤模型,根据评估标准,筛选符合脊髓损伤后神经源性膀胱标准的动物模型纳入模型组和隔姜灸组;假手术组仅切除T10椎板,不破坏脊髓;各组均纳入10只SD大鼠。三组术后均给予抗感染、创口护理及Crede手法辅助排尿。隔姜灸组同时行隔姜灸治疗,即术后第1天开始,每日1次,每次每个穴位灸10 min,连续12 d。 结果 隔姜灸组治疗后嘌呤能P2X3受体的相对表达水平及M2、M3乙酰胆碱mRNA的相对表达水平显著高于模型组（均P＜0.05）。 结论 隔姜灸治疗可提高脊髓损伤大鼠脊髓神经节嘌呤能P2X3受体及膀胱组织中M2、M3乙酰胆碱mRNA的表达水平,从而有利于改善神经源性膀胱功能障碍。     

细胞间粘附分子-1在间质性膀胱炎大鼠动物模型膀胱炎症中的作用

目的探索间质性膀胱炎(IC)大鼠膀胱组织中细胞间粘附分子-1与膀胱炎症反应的关系及其作为IC治疗新靶点的价值所在。方法雌性SD大鼠分为对照组、模型组和抗体治疗组,腹腔注射环磷酰胺联合膀胱灌注鱼精蛋白和脂多糖构建IC的大鼠模型,模型鼠膀胱灌注抗ICAM-1抗体进行治疗为抗体组。比较各组大鼠膀胱组织的炎症反应程度、肥大细胞浸润数目以及膀胱组织中P2X3、PGE2、EP2受体、TNF-α和ICAM-1的表达水平。结果模型组大鼠膀胱组织炎症程度、肥大细胞浸润数目以及P2X3、PGE2、EP2受体、TNF-α和ICAM-1的表达水平均显著高于对照组;当IC模型大鼠给予抗体治疗后,所有指标较模型组均显著显下降,且同对照组相比无显著差异。此外ICAM-1与膀胱组织炎症程度和肥大细胞浸润数目均呈正性相关。结论ICAM-1在IC膀胱组织的炎症反应中起到关键性作用,有望成为治疗IC患者膀胱组织反应的新的靶向分子。     

膀胱黏膜上皮与膀胱过度活动症关系的研究进展

随着越来越多的膀胱过度活动症患者被明确诊断,膀胱过度活动症逐渐成为了人们研究的热点.既往的研究主要集中在神经和逼尿肌的病变对膀胱过度活动的影响.近些年来膀胱黏膜上皮与膀胱过度活动症的关系越来越受到人们的重视,同时膀胱黏膜上皮中也发现了越来越多的受体如神经生长因子、P2X3受体、辣椒素受体TRPV1.阐明膀胱黏膜上皮及这些受体与膀胱过度活动的作用机制对于临床治疗和开发新药具有重要的意义.本文就膀胱上皮黏膜屏障及膀胱黏膜上皮中一些研究较多的受体:神经生长因子、P2X3受体、辣椒素TRPV1受体等作一综述.     

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.     

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.