植入式葡萄糖传感器膜材料壳聚糖与Nafion的组织相容性比较

背景：壳聚糖是天然高分子多糖,可单独或者与其他材料复合制作敷料、药物、基因载体、生物涂层、组织工程支架、传感器膜材料等。 目的：了解壳聚糖作为植入式葡萄糖传感器膜材料的组织相容性,并与Nafion膜进行对比。 方法：制备壳聚糖膜并对其理化性质进行表征,比较壳聚糖膜皮下植入与肌肉植入、Nafion膜肌肉植入的生物相容性。 结果与结论：壳聚糖膜的厚度、溶胀率、表观密度等理化参数可以通过浓度、铸膜液体积来控制;壳聚糖膜能生物降解,63 d皮下植入的降解率为(17.0±9.9)%,说明壳聚糖的体内降解速度较慢。壳聚糖膜皮下植入引起的炎症反应较肌肉植入重,63 d后形成的纤维包膜比肌肉植入要厚(P < 0.05);肌肉植入Nafion与壳聚糖膜引起材料周围纤维包膜厚度差异无显著性意义(P > 0.05),两者均在15 d以后趋于稳定。证明壳聚糖膜能生物降解,与Nafion膜均有较好的组织相容性。     

皮下植入式葡萄糖传感器的研究进展

实时、连续检测葡萄糖可以有效减少和降低胰岛素依赖型的糖尿病患者低血糖症和高血糖症的并发症的发生。现在已有许多研究者在进行皮下植入式血糖测量传感器的研究 ,但到目前还没有可供临床上使用的皮下植入式葡萄糖传感器面世。目前正在研究的可连续测量皮下组织葡萄糖浓度的植入式葡萄糖传感器分可短期植入和长期植入两种 ,研究传感器的短期植入的特性研究者较多 ,并且大部分的传感器在植入后其灵敏度性能很快变坏。这可能是传感器在离体测试中并没有考虑传感器的生物兼容性。本文主要分析在复杂的在体情况下植入式葡萄糖传感器的失效机制     

皮下植入式葡萄糖传感器的研究进展

实时，连续检测葡萄糖可以有效减少和降低胰岛素依赖型的糖尿病患低血糖症和高血糖症的并发症的发生。现在已有许多研究在进行皮下植入式血糖测量传感器的研究，但到目前还没有可供临床上使用的皮下植入式葡萄糖传感器面世，目前正在研究的可连续测量皮下组织葡萄糖浓度的植入式葡萄糖传感器分可短期植入和长期植入两种，研究传感器的短期植入的特性研究较多，并且大部分的传感器在植放后其灵敏度性能很快变坏，这可能是传感器在离体测试中并没有考虑传感器的生物兼容性。本主要分析在复杂的在体情况下植入式葡萄糖传感器的失效机制。     

可植入式葡萄糖传感器数学模型的研究

本研究介绍一种可植入的葡萄糖传感器的设计和计算机模拟优化。葡萄糖传感器采用在氧电极上固定葡萄糖氧化酶层和另一氧参比电极制成。考虑到葡萄糖传感器植入体内时的环境氧浓度较低，而葡萄糖浓度较高，所以采用特殊的酶膜结构，以提高葡萄糖传感器的测量范围，用计算机对葡萄糖传感器的结构和参数进行了模拟优化处理，确定了酶膜的结构尺寸。并用计算机模拟仿真葡萄糖传感器的葡萄糖和氧的传递时间特性和静态特性。     

人绒毛膜促性腺素（HCG）高分子生物活性膜的研制及其在HCG…

本文对固定ＨＣＧ抗体的醋酸纤维素（ＣＡ）生物活性膜的制造和在ＨＣＧ测定中的应用进行了研究。采用乙二胺、丁二胺、乙二胺和癸二胺等烷基二胺与戊二醛的缩合产物作机械掺杂物，以引起可与蛋白质分子耦联的活性基因。掺入已二胺的缩合产物的ＣＡ生物活性膜具有稳定的物理性能、高的生物活性（５５％－６０％）和快的电化学响应速（２－５ｍｉｎ）。用此膜构成的酶免疫传感器与放射免疫法测定ＨＣＧ的结果相比，两者具有良好的相关     

脉冲式微透析法葡萄糖传感器系统：部分体外实验

为构建一小型的皮下组织葡萄糖传感器系统，简化其葡萄糖监测前后的校正过程，改进其温度特性，本研究采用了脉冲式微泵和微透析技术，在５－５ｍＭ及１０ｍＭＧ．Ｓ中对这个葡萄传感器系统进行了葡萄糖恢复的实验。在２０４０℃的范围，每５℃为一阶梯进行渐增渐减温度实验。结果显示葡萄糖恢复达（９７±２）％；传感器输出电流虽随温度的增高而增加，但温度系数仅３－４％。本系统具有体积小，校正简便的特点，能克服温度的干扰而适用于发热的糖尿病患者血糖的监测。     

纳米酶在葡萄糖分析检测中的应用研究进展

即时、准确的监控血糖和尿糖的变化对于糖尿病的早期诊断及血糖控制具有重要意义。自从2004年报道金纳米簇具有磷酸转移酶样催化活性以来,多种具备酶样催化活性的纳米材料被发现,包括过氧化物酶、过氧化氢酶、超氧化物歧化酶、氧化酶等。与天然酶相比,纳米酶具有成本低廉、制备简单、易于保存运输、环境耐受性高等优点。利用纳米酶进行葡萄糖分析检测有望降低检测成本,提高检测系统稳定性。本文总结了金属纳米颗粒、金属氧化物、金属硫化物、碳基材料以及复合材料等多种纳米酶检测系统在葡萄糖分析检测中的特点、检测限和检测范围,并对纳米酶研究面临的挑战及前景进行展望。     

人绒毛膜促性腺素（HCG）高分子生物活性膜的研制及其在HCG测定中的应用

本文对固定ＨＣＧ抗体的醋酸纤维素（ＣＡ）生物活性膜的制造和在ＨＣＧ测定中的应用进行了研究。采用乙二胺、丁二胺、己二胺和癸二胺等烷基二胺与戊二醛的缩合产物作机械掺杂物，以引进可与蛋白质分子耦联的活性基因。掺入己二胺的缩合产物的ＣＡ生物活性膜具有稳定的物理性能、高的生物活性（５５％—６０％）和快的电化学响应速度（２－５ｍｉｎ）。用此膜构成的酶免疫传感器与放射免疫法测定ＨＣＧ的结果相比，两者具有良好的相关性。     

测定人绒毛膜促性腺素(HCG)的酶免疫传感器的研制

本文研制了固定HCG抗体的醋酸纤维素生物活性膜。采用夹心法在膜上发生免疫化学反应,将形成夹心结构的膜,安装在氧电极上,构成酶免疫传感器。耦联过氧化物酶的膜,催化分解H_2C_2致使传感器的输出电流提高,表示为溶液O_2含量的增高。通过溶液中O_2含量的变化值ΔC_2,测定HCG的浓度。被测HCG的浓度范围为5～2500mIU/ml。酶免疫传感器与放射免疫测定相比较,两种方法具有高度相关性,相关系数r=0.998,P<0.001。     

基质胶对植入式葡萄糖传感器外膜材料壳聚糖生物相容性的影响

异物反应的存在导致植入式葡萄糖传感器难以持续正常工作,壳聚糖具有无毒可降解、生物相容性良好等特性,可作为传感器外层的保护膜以提高设备的生物相容性,但尚不能满足实际需求,希望进一步提高膜材料的生物相容性,为此探究不同浓度的基质胶对多孔壳聚糖膜生物相容性的影响。利用模板浸取法,以硅胶作为致孔剂制作多孔壳聚糖膜(PCSM),在此膜的表面滴涂不同浓度的基质胶(matrigel),蛋白质浓度分别为10、15、20 mg/mL。将单独的PCSM(对照组)与滴涂基质胶的PCSM组(实验组)一同植入到SD大鼠背部的皮下组织。植入7、14、28、42、56、70 d后,取材制备常规石蜡切片并进行苏木精-伊红染色,利用组织形态学和统计学方法(主要运用单因素方差分析和Bonferroni法比较两组数据间的差异),对膜外炎性细胞比、纤维包膜厚度和血管密度等数据进行统计分析,评价材料的生物相容性。形态学观察,植入第7、14 d时,膜材料周围细胞核染色均较深。统计膜外炎性细胞比,滴涂不同浓度基质胶的PCSM组在第7 d时炎性细胞比整体上少于PCSM组,第14 d时这一数值略高于多孔壳聚糖膜组。方差分析结果显示,各组间无明显差异(P>0.05)。第28 d时,纤维包膜开始形成,膜材料周围的炎性细胞减少,一些胶原堆积在膜的表面,并随着时间的延长纤维包膜变得致密;第56和70 d时,纤维包膜厚度降低得较明显,各滴涂基质胶的PCSM组纤维包膜厚度均小于PCSM组。方差分析结果表明,各实验组与对照组间差异显著(P <0.05),运用Bonferroni法进行两两比较后,第42、56、70 d时,对照组与实验组中滴涂基质胶浓度为20 mg/mL的PCSM组差异明显,膜材料靠近皮肤端数据两两组比较的P值分别为0.01、0.035、0.024,靠近肌肉端数据P值分别为0.036、0.047、0.210,其他各组之间两两比较后的差异不显著(P>0.05)。膜外血管密度各浓度组大体随着时间的延长呈现增加的趋势,各实验组与对照组间比较差异不大,但个别数据差异明显,滴涂基质胶的PCSM周围血管密度有的值低于PCSM。整体来看,基质胶能提高多孔壳聚糖膜的生物相容性,进一步提高膜材料的性能。     

无创性动态测定血糖的动物实验

探索一种无创性动态测定血糖的原理和建立实验方法。使用共价键固定法 ,制作葡萄糖氧化酶传感器 ,选择传感器最佳制作方法和稳定的工作条件。设立超声前、后组 ,注射葡萄糖前、后及高频、低频超声对照组。在 10只日本大耳兔的皮肤表面 ,用高频或低频超声波处理皮肤 5 m in后 ,用葡萄糖氧化酶传感器测定其微电流信号的变化。采用葡萄糖氧化酶传感器和微电流检测仪 ,可观察到经超声波处理后 ,兔皮肤表面 ,微电流信号明显增高变化(P<0 .0 1)和在注射葡萄糖后的进一步增高变化 (P<0 .0 1)。兔皮肤表面经超声波处理后 ,对葡萄糖的通透性明显增高 ,经葡萄糖氧化酶传感器转化为微电流信号的变化 ,与兔体内的葡萄糖水平呈正相关。在活体动物皮肤表面 ,用葡萄糖氧化酶传感器测定血糖是可行的     

Glucose biosensors based on oxygen electrode with sandwich-type membranes

A glucose biosensor based on an amperometric oxygen electrode has been developed. Polycarbonate and Silastic membranes were assembled (glued together) to form a multilayer sandwich glucose diffusion barrier. The effects of the glue layer composition and thickness of the Silastic membrane on sensor response parameters have been investigated in order to optimize the sensor. The parameters measured were the sensitivity, the concentration range of the linear dependence of the sensor response to glucose, and the long-term operation time. The sensors with the sandwich-type glucose diffusion membrane (Silastic membrane prepared from 20% Silastic suspension, glue layer prepared from polyurethane, 0.5 w/v % in THF solution and standard polycarbonate membrane) demonstrated linearity of response up to 520 mg/dl glucose at 25°C and up to 400 mg/dl at 37°C. These sensor showed good reproducibility of response without significant interference effects (from 1 to 5% of the background current value). The long-term continuous operational time of the sensors was over 40 days at 37°C, and over 60 days at 25°C.     

Glucose kinetics during prolonged exercise in euglycaemic and hyperglycaemic subjects

To determine the limits to oxidation of exogenous glucose by skeletal muscle, the effects of euglycaemia (plasma glucose 5 mM, ET) and hyperglycaemia (plasma glucose 10 mM, HT) on fuel substrate kinetics were evaluated in 12 trained subjects cycling at 70% of maximal oxygen uptake (VO_{2, max}) for 2 h. During exercise, subjects ingested water labelled with traces of U-¹⁴C-glucose so that the rates of plasma glucose oxidation (R _ox) could be determined from plasma ¹⁴C-glucose and expired ¹⁴CO₂ radioactivities, and respiratory gas exchange. Simultaneously, 2-³H-glucose was infused at a constant rate to estimate rates of endogenous glucose turnover (R _a), while unlabelled glucose (25% dextrose) was infused to maintain plasma glucose concentration at either 5 or 10 mM. During ET, endogenous liver glucose R _a (total R _a minus the rate of infusion) declined from 22.4±4.9 to 6.5±1.4 mol/min per kg fat-free mass [FFM] (P<0.05) and during HT it was completely suppressed. In contrast, R _ox increased to 152±21 and 61±10 mol/min per kg FFM at the end of HT and ET respectively (P<0.05). HT (i. e., plasma glucose 10 mM) and hyperinsulinaemia (24.5±0.9 U/ml) also increased total carbohydrate oxidation from 203±7 (ET) to 310±3 mol/min per kg FFM (P<0.0001) and suppressed fat oxidation from 51±3 (ET) to 18±2 mol/min per kg FFM (P<0.0001). As the rates of oxidation at more physiological euglycaemic concentrations of glucose were limited to 92±9 mol/ min per kg FFM, and were similar to those reported when carbohydrate is ingested, the results of the current study suggest that the concentrations of glucose and insulin normally present during prolonged, intense exercise may limit the rate of muscle glucose uptake and oxidation.     

Mutational and Pharmacological Alterations of Neuronal Membrane Function Disrupt Conditioning in Drosophila

Neuronal membrane channels of Drosophila melanogaster were altered either genetically or pharmacologically in order to investigate the role of specific ionic currents in the acquisition and retention of a conditioned behavior. Conditioning could not be detected for Shaker mutants, in which the fast transient potassium current (I_A) is altered; a second potassium channel mutant, eag (ether a go-go) is conditioned like wild type, but the retention period is abnormally short. The nap^ts mutant (no action potential, temperature sensitive), in which nerve excitability is reduced, also expresses normal acquisition and a shortened period of retention. Double mutants of Sh⁵ and nap^ts as well as Sh⁵ treated with tetrodotoxin, are essentially normal with respect to acquisition; in both cases these flies remain retention-defective. These experiments therefore reveal a behavioral phenotype of Drosophila mutants in which the primary physiological defect seems to be in the functioning of specific neuronal ionic channels.     

A microelectrode for continuous monitoring of glucose concentration in isolated perfused tubule segments

The design and the application of a micro-enzyme-electrode for continuous monitoring of glucose concentration in the isolated tubule preparation is described. The principle of the electrode is the amperometric detection of hydrogen peroxide, which is a product of the oxidation ofd-glucose by glucose oxidase immobilized at the tip of a micro-electrode. The resulting current causes a voltage deflection across a resistor in series with the electrode that is correlated directly with the glucose concentration. The electrode response to glucose is almost linear over the concentration range from 0 to 12 mmol/l with a slightly diminished slope in the higher range. Other sugars (12 mmol/l raffinose, galactose, fructose, sucrose, mannitol), pH (from 6.5 to 8.0) andpCO₂ (from 1 to 10 kPa) do not influence the reading. A reduction ofpO₂ in the test solution to 1 kPa blunts the reading. Raising the temperature from 20°C to 40°C leads to a pronounced increase of the voltage deflection at a given glucose concentration. Interference is observed with strongly reducing agents such asl-cysteine, ascorbic acid and uric acid. At defined conditions the electrode is well suited to measure continuously glucose concentration in the luminal fluid at the collection site of the isolated perfused tubule of the kidney. Experiments are presented which illustrate the performance of the glucose electrode in this isolated tubule set-up. Peritubular reduction of potassium concentration or the application of ouabain diminish glucose reabsorption.Supported by Österreichischer Forschungsfonds, Proj. No. 4366 Part of the data was presented at the 55th Meeting of the German Physiological Society, Innsbruck, 1981, Abstract. No. A228. 16th Annual Meeting of the European Society for Clinical Investigation, Luxembourg, 1982, Abstract No. R12. World Congress on Medical Physics and Biomedical Engineering, Hamburg, 1982, Abstract No. 7.03     

妊娠期糖尿病孕妇产后血糖随访的依从性研究

目的探讨影响妊娠期糖代谢异常孕妇产后血糖的高危因素,以加强糖尿病孕妇产后的教育,提高产后血糖检查的随访率。方法160例产前确诊为GIGT和GDM的孕妇,通过宣教和书面嘱托,于分娩后6～8周回院行糖耐量试验,统计随访率,比较随访组与失访组的年龄、学历、家庭收入、分娩方式等指标,分析产后失访的原因。结果160例中120例进行血糖检查,随访率为75%,失访率为25%。随访组的年龄、学历、家族史、剖宫产率、家庭月收入明显高于失访组。随访组OGTT2h血糖大于11.1mmol/L者、新生儿低血糖发生率明显低于失访组。结论医护人员在规范宣教GDM产后随访过程中,应对年轻的、本科以下学历的、无糖尿病家族史的GIGT和GDM孕妇加强产后糖代谢检查的宣教工作。     

医学中的光纤干涉仪

光纤传感器的优点是众所周知的,它已经成为传感器的一大分支.光纤传感的方式主要分为强度型和相位型,强度型的传感器比较多,它的装置简单,易于实现;相位型的需要光纤干涉仪,一般比较困难,但它的精度比较高.相位型传感技术在医学中的应用,主要有:强相干技术,弱相干技术,以及部分相干技术(PCI).它们的代表应用分别有:高强度超声波光纤干涉传感器,光干涉成像技术(OCT),基于PCI的眼科生物测试仪等.