Hepatic Disposition Characteristics of Electrically Charged Macromolecules in Rat in Vivo and in the Perfused Liver

The effect of electric charge on the hepatic disposition of macromolecules was studied in the rat. Charged derivatives of dextran (T-70) and bovine serum albumin (BSA), mitomycin C–dextran conjugates (MMC-D), and lactosaminated BSA (Lac-BSA) were employed as model macromolecules. After intravenous injection, cationic macromolecules were rapidly eliminated from plasma because of their extensive hepatic uptake, while anionic and neutral macromolecules were slowly eliminated. Cationic macromolecules were recovered from parenchymal and nonparenchymal hepatic cells at a cellular uptake (per unit cell number) ratio of 1.4–3.2, while that of Lac-BSA was 14. During liver perfusion using a single-pass constant infusion mode, cationic macromolecules were continuously extracted by the liver, with extraction ratios at steady-state (E _ss) ranging between 0.03 and 0.54, whereas anionic and neutral macromolecules were almost completely recovered in the outflow at steady state. The E _ss for cationized BSA (Cat-BSA) and cationic MMC-Dcat were concentration dependent and decreased at low temperatures and in the presence of colchicine and cytochalasin B. The possible participation of the internalization process in the uptake of cationic macromolecules by hepatocytes was suggested.     

MR Lymphography with a Lymphotropic T1-Type MR Contrast Agent: Gd-DTPA-PGM

A model system of a paramagnetic lymphotropic MR contrast agent (Gd-DTPA labeled polyglucose associated macrocomplex, PGM) for T¹-weighted MR imaging of lymph nodes in rats and rabbits was evaluated. Pharmacokinetic (tissue accumulation) and MR imaging data (optimal dose and timing parameters) were obtained in normal rats (n = 88) after subcutaneous (SC) injection of paramagnetic, radiolabeled [111In]Gd-DTPA-PGM. A rabbit model of lymph node metastases (n = 8) was ultimately used to demonstrate the potential of MR imaging with Gd-DTPA-PGM for nodal tumor detection. Maximum concentrations of Gd-DTPA-PGM were found in popliteal and paraaortic lymph nodes within 24 h after SC administration, and highest lymph node SNR values were obtained by MR imaging at this time point. The optimum imaging dose was 6–12 μmol Gd/kg. Tumor-lymph node contrast increased from 0.0 ± 1.2 precontrast to 19.2 ± 6.5 (spoiled gradient echo sequence, TR 50/TE 7/flip angle 60°) postcontrast and conspicuity of nodal metastases was improved. Gd-DTPA-PGM accumulates in lymph nodes after SC administration and significantly enhances lymph node signal intensity of normal animals but not metastatic lymph nodes.     

鼻腔止血器用于鼻腔填塞止血的疗效分析

目的分析比较高分子止血海绵和鼻腔止血器在鼻内镜术后的止血效果。方法选取100例需要进行鼻腔、鼻窦手术患者,其中男性76例,女性24例;年龄18~60岁,中位年龄36岁。随机分为2组,试验组50例,对照组50例。在术后分别放置高分子止血海绵和鼻腔止血器,观察患者的疼痛反应和止血效果,并对比取出填塞物时的难易程度及出血量,进行对比分析。结果两者止血效果相当,试验组少量渗血36例,对照组29例;两组无出血病例;止血效果两组差异无统计学意义(P0.05)。试验组无痛、轻度疼痛各26、24例,对照组各3、44例。试验组填塞物容易取出46例,对照组21例。两组在鼻腔胀痛、头痛、抽出时难易程度、抽出时出血量方面的差异均有统计学意义(P0.05),均显示试验组的效果优于对照组。结论鼻腔止血器不良反应少,临床效果优于高分子止血海绵填塞,值得广泛推广。     

黄连解毒汤模拟体系的超滤膜过程研究

目的:以黄连解毒汤模拟体系为研究对象,探讨中药水提液超滤过程污染机制,为中药膜分离技术应用系统的优化设计奠定基础.方法:采用系统模拟的方法,以超滤膜过程中通量变化、膜污染度、成分截留率、小分子物质吸附速率和吸附量等为指标,研究黄连解毒汤复方中小分子药效物质和共性高分子物质的超滤行为及相互影响.结果:黄连解毒汤模拟体系中,小檗碱和栀子苷PS5K超滤膜透过率在90%以上,淀粉、果胶、蛋白质3种高分子物质的截留率为100%;但模拟溶液中由于高分子物质的存在造成小檗碱和栀子苷的膜透过率大大降低,膜污染和膜通量衰减加剧;小檗碱和栀子苷的膜吸附行为也因为高分子物质的存在而发生了改变.结论:黄连解毒汤复方溶液中,高分子物质的存在是造成超滤膜污染和药效物质损失的主要因素,其中主要污染物是淀粉和果胶.     

氢化泼尼松缓释注射剂研究

目的 应用天然可降解高分子材料为基质，制备可注射氢化泼尼松缓释注射剂。方法 采用胶原、壳聚糖、明胶三种天然生物高分子材料，通过复合乳化-交联法制备氢化泼尼松微胶囊缓释注射剂。结果 在显微镜下观察所制备的含药微胶囊，呈密封球状，微胶囊中心含有针状药物晶体，微胶囊平均粒径66．2μm。结论 三种天然高分子材料制备的微胶囊可成功包裹氢化泼尼松，并具有适用注射的粒径。     

Transvascular and interstitial transport of a 19 kDa linear molecule in human melanoma xenografts measured by contrast-enhanced magnetic resonance imaging.

Cancer therapy involving blood-borne macromolecular therapeutic agents often fails, owing to inadequate macromolecule uptake in malignant tissue. The transvascular and interstitial transport of a 19 kDa linear molecule (NC22181 or poly-[Gd-DTPA]-co-[1,6-diaminohexane]) was studied in the present work in an attempt to identify transport barriers limiting the delivery of macromolecules to tumors. Tumors of four human melanoma xenograft lines were included in the study. The uptake of NC22181 was measured by spoiled gradient recalled magnetic resonance imaging (MRI). The effective microvascular permeability constant and the interstitial influx constant of NC22181 were calculated from NC22181 uptake curves by using a three-compartment tissue model. The uptake of NC22181 was limited by the interstitial transport and not by the transvascular transport in all xenograft lines. If the melanoma xenografts used in this study are representative models of human cancer, our results suggest that strategies for increasing the delivery of macromolecular therapeutic agents to tumors should focus on improving the transport conditions in the interstitium, rather than enhancing the permeability of the microvascular wall.     

生物序列比对算法与图形硬件加速研究

探索准确、高效、低成本、通用性并存的生物序列比对方法.将点阵图算法、启发式算法等各种序列比对算法中准确性最高的动态规划算法在计算机中实现,并通过流模型将其映射到图形硬件上,以实现算法加速;通过数据库比对搜索实例,进行比对时间和每秒百万次格点更新(MCUPS)性能值评测.结果表明,该加速算法在保证比对准确性的同时,能较大地提高比对速度.与目前最快的启发式算法相比,比对平均加速为18倍,最高加速可达28倍.     

骨组织工程支架材料

寻找理想的支架材料是目前骨组织工程研究的热点。本文对用于骨组织工程支架材料的高分子材料、陶瓷材料、天然生物衍生材料及两者的复合材料等的研究现状进行综述，并分析了这些材料的优缺点及骨组织工程支架材料发展趋势。     

Quantitative proton short-echo-time LASER spectroscopy of normal human white matter and hippocampus at 4 Tesla incorporating macromolecule subtraction.

Accurate quantification of in vivo short-echo-time (TE) (1)H spectra must account for contributions from both mobile metabolites and less mobile macromolecules, which can fluctuate in disease. The purpose of this study was to develop an approach for the acquisition and processing of macromolecule information to optimize metabolite quantification accuracy and precision. Human parietal white matter (8-cm(3) voxel) and posterior hippocampus (1.7-cm(3) voxel) metabolite levels were quantified, following manomolecule subtraction, from short-echo-time spectra (TE = 46 ms) acquired at 4.0 Tesla with localization by adiabatic selective refocusing (LASER). Nineteen metabolites were fit using a time domain Levenberg-Marquardt minimization that incorporated prior knowledge of metabolite lineshapes. The macromolecule contribution to the spectrum was reduced by 87% (P < 0.05) when the acquisition of single averages of the full spectrum and macromolecule spectrum were interleaved to reduce subtraction errors due to motion. Subtracting the Hankel Lanczos singular value decomposition (HLSVD) fit of the macromolecule spectrum, which contained no random noise, did not alter quantified metabolite levels but did not increase metabolite quantification precision. Several metabolites had higher concentrations in the posterior hippocampus compared to parietal white matter, which emphasizes the need to carefully control for partial volume contamination in hippocampal spectroscopy studies.     

聚(苯乙烯-环氧乙烷)嵌段大单体的合成、表征及其共聚合的研究

以异丙基苯钾(n-Cumyl potassium)作引发剂,α-甲基丙烯酰氯为终止剂,用阴离子聚合方法合成了一系列不同分子量、不同组成的新型聚(苯乙烯-环氧乙烷)(疏水-亲水型)嵌段大单体[Poly(St-b-Eo)-MA magromer]。用红外光谱及核磁共振进行了鉴定并测定了它的数均官能度(?)_n,对大单体与苯乙烯、甲基丙烯酸甲酯和甲基丙烯酸在不同条件下的共聚反应也进行了研究。发现反应条件对大单体和烯类单体的共聚速率均有很大影响。