复合淀粉微球的合成与表征

以玉米淀粉β-环糊精为原料合成复合淀粉微球.通过IR、SEM分析及粒度分析仪(LAP)对微球进行表征.结果表明:制备的微球产率高达88.36%,且颗粒分散性好、表面较光滑、粒径分布较窄,其中14～142μm占80%,7～37 μm占50%以上.     

兔肝肿瘤动脉化疗中戊脉安和淀粉微球的调变作用

目的 研究戊脉安和淀粉微球肝动脉灌注化疗药物浓度的调变。方法 以新西兰兔肝ＶＸ－２肿瘤动脉化疗对象测定阿霉素分布改变。结果 ２ｍｇ／ｋｇ戊胺安引起血压下降和心率缓慢，肿瘤和心脏的阿霉素浓度提高，１０ｍｇ／ｋｇ淀粉微球对心血管无影响，在提高肿瘤内阿霉素浓度的同时可降低肝组织和心脏的阿霉素浓度，使阿霉素的肝比例自０．４上升为１．０１（Ｐ〈０．０５）。戊脉安和可降解淀粉微球协同作用不明显。结论 肝动脉化     

可降解淀粉微球吸附薄荷油的研究

用可降解淀粉微球吸附薄荷油制得了包合物，建立了包合物中薄荷油的快速测定方法——紫外分光光度法。测定了吸附时间和投油量对饱和吸附量的影响。结果表明：该方法快速、准确、重复性好、操作简便。吸附2h，薄荷油体积分数为4％时，饱和吸附量84．74μL／g淀粉微球。     

可降解淀粉微球动脉栓塞机制的动态研究

目的 动态研究可降解淀粉微球(DSM)动脉栓塞的机制。方法10只大鼠，经肠系膜上动脉注入DSM微粒后，应用荧光显微镜观察小肠黏膜终末小动脉内DSM微粒的动态变化及相应血流改变。结果DSM可在动脉内形成大小不等的铸型，栓塞于不同大小的终末小动脉。DSM以碎片的形式降解。随着DSM的降解，终末小动脉内血流可完全恢复。结论经动脉注入后，DSM降解主要表现为在涡流冲击下的物理裂解过程．随着DSM及其裂解碎片进一步降解，小动脉再通。     

京尼平与戊二醛交联明胶微球的性能比较

目的 比较京尼平(genipin,GP)及戊二醛(glutaraldehyde,GA)交联明胶微球的性能,探讨GP交联明胶微球的优缺点.方法 以改进的双相乳化冷凝聚合法制备明胶微球,分别以GP、GA进行交联.取60%交联度的GP及GA明胶微球,分散于PBS中,比较其粒径外观、溶胀及降解性能.两种交联明胶微球分别携载rhBMP-2,测定载药量及包封率,观察10 d内的药物缓释性能.收集GP及GA明胶微球浸提液,倍比稀释成100%、50%、25%浓度,分别与小鼠成骨细胞共培养2 d,以DMEM组为阴性对照组,MTT法检测细胞增殖,测定GP及GA微球的细胞毒性.结果 GP及GA交联明胶微球在溶液中均呈规则圆形,粒径分别为(78±18)、(65±10)μm,GP交联明胶微球分散性更佳.当交联度均为60%时,GP交联明胶微球溶胀率为89.0%±4.8%,显著低于GA交联明胶微球(118.0%±7.6%),差异有统计学意义(P<0.01);GP及GA交联明胶微球分别于28、21 d完全降解,两者比较差异有统计学意义(P<0.05).GP及GA交联明胶微球载药量分别为(921±73)、(965±62)ng/g,包封率分别为88.5%±2.1%、89.7%±1.8%,两者比较差异均无统计学意义(P>0.05).GP及GA交联明胶微球10 d累积释药百分率分别为78.80%±4.96%、90.50%±5.12%,两者比较差异有统计学意义(P<0.05).当浸提液浓度为25%、50%、100%时,GP交联明胶微球细胞毒性均为Ⅰ级,GA交联明胶微球细胞毒性分别为Ⅱ、Ⅲ、Ⅲ级.结论 与GA交联明胶微球比较,GP交联明胶微球的综合性能更优越,可应用于组织工程领域.     

rh-BMP-2壳聚糖微球的制备及体外检测

[目的]以壳聚糖为辅料,通过乳化交联法制备新型重组人骨形态发生蛋白-2缓释微球,并对其粒径、载药、体外释药、理化特性及降解特性进行检测,以评估应用生物可降解的壳聚糖微球作为BMP-2缓释载体的可行性.[方法]以京尼平作为交联剂,应用乳化交联法制备具有控制释放功能的负载rhBMP-2壳聚糖微球,应用扫描电镜观察微球的形态和粒径;利用酶联免疫吸附实验(ELISA)动态检测BMP-2壳聚糖微球的载药率、包封率和缓释规律以分析微球的缓释能力.[结果]乳化交联法制备的壳聚糖微球,球形良好,球体表面光滑,具有较高的包封率(>85%).体外药物释放试验表明,rhBMP-2可以从壳聚糖微球中缓慢释放,整个释放过程可达30 d.[结论]应用乳化交联法制备的负载rhBMP-2壳聚糖缓释微球,具有很好的控制释放rhBMP-2的能力.这种新型药物控制释放系统在细胞因子的控制释放及骨组织工程中有潜在的应用价值.     

bFGF壳聚糖微球的制备及检测

目的探讨以壳聚糖为载体、采用乳化交联法制备的bFGF壳聚糖微球体外释放特性,为下一步实验奠定基础。方法应用0.6%三聚磷酸钠溶液作为交联剂,1.5%壳聚糖溶液作为载体,采用乳化交联法制备bFGF壳聚糖微球。激光粒度及Zeta电位分析仪检测微球粒径分布,扫描电镜观察形态;ELISA法计算bFGF壳聚糖微球载药量、包封率及体外释药规律。结果 bFGF壳聚糖微球粒径为20.312～24.152μm;扫描电镜观察显示微球表面光滑圆整,无明显孔隙,分布均匀,分散性好。载药量和包封率分别为(7.57±0.34)mg/g及95.14%±1.58%。bFGF壳聚糖微球可持续体外释放bFGF 24 d;bFGF浓度随时间延长逐渐升高,第24天达(820.45±21.34)ng/mL;微球体外释药具有突释效应,突释率为18.08%,24 d累计释放率为82.05%。结论乳化交联法制备bFGF壳聚糖微球操作简便,微球表面光滑、分布均匀,分散性好,载药量和包封率均较高,体外释药较稳定且释放率较高,是一种较理想的制备bFGF壳聚糖微球的方法。     

重组人骨形态发生蛋白-2壳聚糖纳米微球的制备及检测

目的 制备负载重组人骨形态发生蛋白-2(rhBMP-2)壳聚糖纳米微球,并检测其粒径、形态、降解及药理特性,以评估壳聚糖纳米微球作为rhBMP-2缓释载体的可行性.方法 以壳聚糖为原料、三聚磷酸钠为交联剂,通过离子交联法制备负载rhBMP-2壳聚糖纳米微球,应用透视电镜观察微球的形态、激光粒径,分析其粒径分布、溶菌酶降解,了解降解特性.通过酶联免疫吸附实验(ELISA)检测rhBMP-2壳聚糖微球的载药率、包封率和释药规律.结果 离子交联法制备的壳聚糖纳米微球,平均粒径大小为230nm,成球性较好,包封率和载药率分别为(66.867±4.575)％、(33.437±2.290)μg/mg;体外释药试验rhBMP-2可以从壳聚糖纳米微球中缓慢释放,释放行为符合双向动力学规律,整个释放过程可达30 d.结论 离子交联法可成功制备壳聚糖纳米微球并具有缓释rhBMP-2的能力,为进一步应用于骨组织工程研究提供实验依据.     

可生物降解止血粉的制备及其止血性能

目的采用壳聚糖(chitosan,CTS)为主要材料制备一种可生物降解止血粉并观察其止血性能。方法以可降解的天然有机高分子材料CTS为主材,海藻酸钠(alginate,ALG)为辅料,通过乳化交联工艺,制成一种结构疏松的微球。利用单颗粒光学传感技术测定微球粒径,扫描电镜观察干燥微球的超微结构,将其置于伤口渗出液中浸泡,分别于1、3、5、10、20、30和60min后测定微球溶胀率。以云南白药为对照,在6只新西兰兔的脾出血模型,随机使用CTS/ALG微球和云南白药进行止血,观察止血效果。结果乳化交联法工艺稳定,CTS/ALG微球形态圆整,粒度均匀,粒径为2～20μm,平均粒径为4.05±2.55μm。干燥态CTS/ALG微球呈白色粉体状,结构疏松,扫描电镜下可见其呈珊瑚状外观,表面布满皱折。CTS/ALG微球的溶胀率,5min时达280.139%。在兔的脾出血模型上CTS/ALG微球组的出血时间为2.83±0.17min,云南白药组为5.33±0.49min,止血效果明显优于云南白药组(P<0.01)。结论以CTS和ALG为材料制备的CTS/ALG微球止血性能良好,使用方便,是一种新型的粉体止血剂。     

壳聚糖微球介导人IL-1Ra与TGF-β1基因转染兔软骨细胞的研究

目的 探讨壳聚糖微球介导人IL-1Ra与TGF-β1基因转染兔软骨细胞.方法 制备壳聚糖微球介导IL-1Ra质粒与TGF-β1质粒转染系统,检测其载药、体外释药、降解,转染体外培养的兔膝软骨细胞,荧光显微镜、荧光定量PCR、MTT检测.结果 壳聚糖-IL-1Ra DNA和壳聚糖-TGF-β1 DNA微球平均径粒(2.8±0.2)μm和(2.6±0.1)μm,包封率(88.3±4.1)%和(87.2±2.6)%;缓释分3个阶段.荧光显微镜观察、荧光定量PCR证实软骨细胞转染基因得到30 d表达.MTT提示转染促进软骨细胞增殖.结论 壳聚糖微球介导IL-1Ra与TGF-β1基因转染软骨细胞可获得较长期目的基因表达,可促进软骨细胞增殖,为用于基因治疗软骨退变和促进软骨修复提供基础.     

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.     

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.     

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.