Mu阿片受体在大鼠"泻剂结肠"肠道低反应中的作用

目的　研究mu阿片受体对“泻剂结肠”大鼠结肠动力的影响 ,“泻剂结肠”大鼠肠道阿片受体含量的变化。方法　以“泻剂结肠”为模型 ,用电刺激离体肌条收缩反应试验、放射性配体结合等方法。结果　外源性增加DAMGO明显抑制电刺激“泻剂结肠”大鼠离体肌体收缩反应 ,收缩波振幅降低 ,这种抑制作用是剂量相关 ,mu阿片受体拮抗剂Naloxone明显加强电刺激“泻剂结肠”大鼠离体肌条收缩反应 ,收缩波振增加 ,与正常组相比 ,“泻剂结肠”大鼠肠道mu阿片受体含量增加。结论　内源性阿片肽通过阿片受体介导参与了慢传输性便秘肠道动力的调控 ,主要是通过mu阿片受体     

Mu阿片受体在大鼠“泻剂结肠”肠道低反应中的作用

目的：研究Mu阿片受体对“泻剂结肠”大鼠结肠动力的影响。“泻剂结肠”大鼠肠道阿片受体含量的变化。方法：以“泻剂结肠”为模型，用刺激离体肌条收缩反应试验，放射性配体结合等方法。结果：外源性增加DAMGO明显抑制电刺激“泻剂结肠”大鼠离体肌体收缩反应，收缩波振幅降低，这种抑制作用是剂量相关，mu阿片受体拮抗剂Naloxone明显加强电刺激“泻剂结肠”大鼠离体肌条收缩反应，收缩波振增加，与正常组相比，“泻剂结肠”大鼠肠道mu阿片受体含量增加，结论：内源性阿片肽通过阿片受体介导参与了慢传输性便秘肠道动力的调控，主要是通过mu阿片受体。     

Mu、Kappa受体激动剂、拮抗剂对大鼠肠道传输功能的影响

目的 :观察 Mu、 Kappa阿片受体激动剂、拮抗剂对大鼠肠道传输功能的影响。方法 :采用大鼠泻剂结肠模型 ,采用活性炭悬液推进法测定肠道传输功能。结果 :“泻剂结肠”组的肠道炭沫推进距离较对照组显著缩短 (P <0 .0 5 )。不同剂量的 Mu阿片受体激动剂均使肠道炭沫推进距离非常显著的短于对照组 (P <0 .0 1)。随 Mu阿片受体拮抗剂剂量的增加 ,测定的炭沫推进距离显著长于对照组 (P <0 .0 5 ,P <0 .0 1)。 kappa阿片受体激动剂和拮抗剂对“泻剂结肠”大鼠肠道传输功能无明显的作用。结论 :阿片受体激动剂和拮抗剂参与了对“泻剂结肠”肠道传输功能的影响 ,主要是通过 Mu阿片受体 ,Kappa阿片受体无明显的作用。     

国外全身麻醉药物进展(二)

二、止痛药阿片类止痛药常与苯甲二氮(艹卓)类、巴比妥类等催眠药合用,除发挥止痛效应外,可加强这些药物的中枢镇静作用。阿片类药物可分为纯激动药和激动—拮抗药(包括纯拮抗药)两大类。已证明有μ(mu)、△(delta)、k(kappa)、∑(epsilon)和Q(sigma)等五种阿片受体。μ受体与止痛、呼吸抑制、缩瞳、冷漠、欣快、成瘾和耐受现象有关。吗啡、芬太尼、苏芬太尼、哌替啶等为μ受体激动药。     

吗啡耐受和依赖时第二信使分子和阿片受体变化及与谷氨酸受体的关系

目的　研究吗啡耐受和依赖时某些第二信使分子和阿片受体变化及与谷氨酸受体的关系。方法　竞争性蛋白结合法、共聚焦显微镜技术和受体结合实验检测 c AMP水平、胞内钙和阿片受体变化。结果　在表达诱导型一氧化氮合酶 c DNA神经细胞中 ,吗啡急性刺激剂量依赖性抑制 c AMP生成 ,慢性用药引起 c AMP代偿性增加。谷氨酸受体拮抗剂 MK80 1增强吗啡的急性抑制效应 ,抑制阿片受体介导 c AMP系统脱敏。对吗啡慢性给药细胞 ,用吗啡刺激和纳络酮戒断引起 [Ca2 ]i增加 ,阿片受体 Kd值增加和 Bmax值减少 ,MK80 1对这些指标的改变没有影响。结论　 MK80 1减轻阿片耐受和依赖的机制可能不是改变阿片受体特性 ,主要与受体后信号转导有关。     

A14125I-胰岛素与H22肝癌细胞胰岛素受体结合的研究

目的体外分析H22肝癌细胞与正常肝细胞膜的胰岛素受体表达,探讨胰岛素作为受体介导靶向治疗载体的可行性及临床应用前景.方法用氯氨T法制备A14125I-胰岛素,电泳分离纯化标记物并用自身置换比放射性测定和过量受体结合实验法鉴定标记物质量,再制备H22肝癌细胞及正常小鼠肝细胞,进行体外受体结合实验,分别测定125I-胰岛素与小鼠H22肝癌及正常肝细胞膜胰岛素受体结合的Kd值及Bmax值以及其竞争结合曲线.125I-胰岛素受体结合的Kd值及Bmax值用t检验分析,饱和结合曲线用Scatchard分析.结果小鼠H22肝癌细胞及正常小鼠肝细胞胰岛素受体Bmax值分别为(5.6±1.1) pmol/106细胞和(3.2±0.8) pmol/106细胞,高亲和力Kd值为(1.8±0.6) nmol/L及(2.1±0.9) nmol/L,低亲和力Kd值为(32.0±10.7) nmol/L及(37.0±12.3) nmol/L.癌细胞胰岛素受体Bmax值明显高于正常肝细胞(P＜0.05).受体结合实验表明,125I-胰岛素与H22肝癌及正常细胞的结合具有特异性.结论 125I-胰岛素与H22肝癌及正常小鼠肝细胞膜受体的结合具有高度特异性,H22肝癌细胞较正常小鼠肝细胞表达胰岛素受体增加,提示胰岛素可作为抗癌载体通过与肝癌细胞表面受体结合而介导肝癌的靶向治疗.     

慢性传输性便秘模型大鼠血清性激素水平及结肠雌激素受体β的分布与表达研究

目的 研究慢性传输性便秘(STC)大鼠血清性激素水平及结肠雌激素受体β(ERβ)的分布与表达变化.方法 建立STC大鼠模型,以电化学发光法、免疫组化及Western blot技术分别检测STC大鼠与正常大鼠血清性激素及结肠ERβ的分布与表达.结果 电化学发光法检测发现,STC大鼠血清促卵泡生成素(FSH),黄体生成素(LH),雌二醇(E2),孕酮(P)及睾酮(Testo)与正常大鼠比较均无统计学差异(均P＞0.05).免疫组化显示,ERβ主要分布于大鼠结肠的肌间神经丛及黏膜下神经丛,且STC大鼠ERβ的表达明显低于正常大鼠.Western blot显示,STC大鼠结肠ERβ蛋白表达较正常大鼠明显降低,差异有统计学意义(P＜0.0l).结论 STC大鼠结肠ERβ蛋白表达量降低,ERβ表达的改变可能参与STC的发病机制.     

烧伤大鼠血清对心脏微血管内皮细胞内皮素受体的影响

为进一步探讨内皮素参与烧伤后病理生理学改变的机制,分离和培养大鼠心脏微血管内皮细胞。分别用正常大鼠和烧伤大鼠(30％TBSAⅢ度)伤后6小时的血清培养心脏微血管内皮细胞12小时,用放射性配基结合受体分析法,观察烧伤血清对心脏微血管内皮细胞膜内皮素受体亲和力及结合容量的影响。结果表明,大鼠心脏微血管内皮细胞膜上只有内皮素受体亚型B分布,该受体的最大结合容量(Bmax)为142±27fmol/mg蛋白,平衡解离常数(Kd)为119±22pmol/L。烧伤血清不影响该受体的Kd值,但使Bmax增加68％,表明烧伤血清上调内皮素受体亚型B。提示烧伤后微血管内皮细胞对内皮素作用的敏感性增加。     

季节因素对大鼠下丘脑和垂体褪黑素受体的影响

目的探索季节变化对大鼠性腺轴褪黑素(MT)受体的影响及其生理机理。方法采用大鼠松果体摘除模型,运用放射性配基饱和法,测定雄性SD大鼠性腺轴褪黑素受体的最大结合量(Bmax)和解离常数(Kd值)的冬夏变化。结果在正常生理条件下,下丘脑和垂体褪黑素受体Bmax值(P<0.05)、Kd值(P<0.01)均表现为冬高夏低。摘除松果体后,除了垂体夏季手术组Bmax值与正常对照组相比没有明显变化(P>0.05),冬、夏季节下丘脑、垂体手术组Bmax值和Kd值都明显高于相应的正常对照组(P<0.01)。而睾丸的褪黑素受体因含量极少而无法测出其与125I-MT特异性结合的Bmax值和Kd值。结论下丘脑、垂体褪黑素受体具有明显的季节性节律变化,松果体可能在此过程中起重要的调节作用。     

慢传输性便秘结肠神经系统的病理生理改变

目的：了解慢性输性便秘（STC）结肠壁神经系统的病理改变。方法：用免疫组化法检测了慢性输性便秘病人结肠肠壁神经元凋亡现象。结果：STC患者结肠壁神经元有凋亡现象发生，神经元内bcl-2含量下降，而bax无显著变化。结论：这种不恰当的细胞死亡－－病理性神经元凋亡可能在STC的发病过程中具有重要意义，提示通过抑制凋亡的发生是预防和治疗STC的一个有效途径。     

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.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

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.     

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.     

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.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.