血液透析膜材料的生物相容性评价

血液透析是终末期肾病患者的主要替代疗法。透析膜是透析器的主要构成部分,透析膜的理化特性决定着透析效果,透析膜的生物相容性直接关系到血液透析患者的生活质量与生存率。随着医学与相关学科技术的发展,透析膜的透析效果、生物相容性逐步提高,血液透析膜的发展已有了长足的进步,但目前的肾替代治疗仍是不完全的,也是非生理性的。如何进一步提供更完全的肾替代治疗,进一步改善肾衰竭患者的远期预后,还有待进一步的深入研究。     

血液透析器复用的研究进展

透析器复用在医疗资源使用、生物相容性改善以及复用技术都有着很好的发展。最近,国家卫生部医政司邀请了国内部分专家,结合我国临床实际,讨论制定透析器复用的操作规范、技术标准和质量要求。这样,我国透析器复用有了更好的发展机会和安全保障。1964年Shaldon首次描述了透析器的复用,随后从蟠管型(Coil)透析器到中空纤维透析器,复用技术逐渐得到规范。1977年美国透析协会报告,接受透析器复用的患者达到了17％,随后     

塑料血袋血液相容性评价进展

1949年美国首次报导使用塑料血袋以来,经过近40年的实践和改进,目前在材料优化、结构改进以及实验研究与临床应用技术等方面均有重大进展。国内1967年研制成功的塑料血袋亦对提高我国输血技术水平、开展成分输血起了重大作用并获得了宝贵经验。塑料血袋作为一种与血液接触的材料,在研制中及临床使用之前须准确评价其与血液的相容性。本文将就此作一综述。一、血液相容性的概念血液相容性是在生物材料研究及评价中一个有争论的概念。美国国立卫生研究院(NIH)在《血液与材料相互作用指南》一书中指出:血液相容性是由材料最终使用的特征来定义的,但研究人员却往往不确定其最终使用条件,而是把血液与材料相互作用实验报告中的数据作为材料最终使用时的结论。     

血液透析膜的生物相容性

通过比较不同种血液透析膜的材料学特点,探讨了血液透析膜相容性的基本条件,将血液透析膜分为纤维素膜和合成膜两种类型,阐述了血液透析膜生物相容性的研究现状。目前各种新型的膜材料在不断地研发,部分已在临床使用或即将问世,如维生素E修饰的透析膜、多黏菌素B修饰的透析膜、甲壳素膜、以及人肾单位透析器和生物活性膜等。研制高通量、高效、生物相容性好的透析膜仍将是今后发展的主要方向。随着高分子材料和纳米技术的不断发展,透析膜的透析效果、生物相容性将逐步提高。     

血液灌流加血液透析的临床应用及护理

血液灌流是将患者的血液引出替外，经过血液灌流器通过吸附作用，清除外源性或内源性毒物，达到血液净化的一种治疗方法。而血液透析是在血液与透析液之间的透析膜利用弥散清除体内溶质或向体外补给溶质的方法。目前，我院采用血液灌流与血液透析联合应用，治疗药物中毒50余例，取得了满意疗效。     

一次性使用滴定管式输液器血液相容性和热源评价试验

评价一次性使用滴定管式输液器的血液相容性,为医疗产品临床安全应用提供依据.对一次性使用滴定管式输液器的样品测定全凝血时间（WBCT）、凝血酶原时间（PT）和部分凝血酶原时间（PTT）、溶血率及细菌内毒素.结果 显示一次性使用滴定管式输液器的样品,WBCT、PT 和PTT与阴性对照比较,均无显著性差异（P＞0.05）,溶血率为1.38%,小于5%,符合医疗器械血液相容性实验要求.内毒素含量均低于0.5EU/mL.一次性使用滴定管式输液器血液相容性良好,无致热源.     

血液透析膜材料的生物相容性

血液透析是急慢性肾功能衰竭主要治疗措施,透析膜材料是影响血液透析治疗效果的关键因素.理想的透析膜应该与血管内皮非常接近,但目前还不能达到这一目标,所以血液和异体的透析膜接触后必然相互作用.文章对透析膜引起补体、白细胞、单核细胞及细胞因子的释放、凝血、血管活性物质、β 2-微球蛋白以及其他方面的变化进行相应探讨.     

小口径人工血管血液相容性

学术背景：大口径人造血管的研究已取得突破性进展，在临床上得到广泛应用。而在小口径人造血管（直径小于6mm）研究方面，由于存在血管栓塞以及生物相容性等方面的核心问题没有得到有效解决，离实际应用还有很大的距离。目的：简单介绍人造血管的研究现状，分析小口径人造血管研制中存在的问题，阐述如何提高血液相容性方法。检索策略：应用计算机检索中国知网（www．cnki.net）及Medline（www.pubmed.com）1975-01／2007-08有关小口径人造血管血液相容性方面的文献，中文检索词“人造血管，聚氨酯，血液相容性”：英文检索词“Vascular grafts，Polyurethane，Blood Compatibillty”。初检得到143篇文献，包括中文28篇，英文115篇。文献评价：阅读标题和摘要进行初筛，排除因研究目的与本研究无关者54篇，内容重复性的研究64篇，保留25篇中英文文献进一步分析。其中动物实验和在体、离体、细胞学实验13篇，综述、述评、讲座类文献12篇。资料综合：①以往用于人造血管制造的主要材料有涤纶、聚四氟乙烯、真丝等，而具备良好的顺应性、耐磨性、弹性、生物相容性及一定的抗凝血性的聚氨酯则是目前被研究最多的人造血管制造材料。②小口径人造血管存在的主要问题是人造血管完全没有抗血栓性，血液流经内腔时，由于血流量小，流速慢，在人造血管腔面易形成附壁血栓，随之血凝亢进，血流更缓慢，血栓层增厚，最终导致人造血管闭塞。③在解决材料的血液相容性问题上，人们对材料表面的修饰研究得较多，然而，处于生物系统中的材料由于接触到体液、有机大分子、酶、自由基、细胞等多种因素，其生物学环境极为复杂，表面修饰的方法对血液相容性的改善有限。因此，应用组织工程的方法在材料表面原位培养人体内皮细胞使材     

高分子材料聚砜膜滤器临床应用及相容性评价

目的:评价高分子材料聚砜膜滤器的性能以及置入体内与宿主的生物相容性,为其在临床上的应用提供参考依据.方法:以"血液透析;透析膜材料;组织相容性;血液相容性;聚醚砜"为中文关键词;以"hemodialysis,dialysis membrane materials:histocompatibility;blood compatibility;polyethersulfone"为英文关键词,采用计算机检索2006-01/2010-03相关文章.纳入与有关生物材料与宿主相容性的文章;排除重复研究或Meta分析类文章.以22篇文献为重点进行探讨聚砜膜滤器材料的性能及应用前景.结果:目前各种新型的膜材料在不断地研发,部分已在临床使用或即将问世,如维生素E修饰的透析膜、多黏菌素B修饰的透析膜、甲壳素膜、以及人肾单位透析器和生物活性膜等.聚砜膜滤器由于具有较好的生物相容性和封堵效果,在临床广泛应用.结论:聚砜膜滤器通过高分子材料滤器强大的对流、黏附作用,高效清除组织损伤过程中产生的炎症递质和毒性代谢产物,排除机体内潴留的多余水分,维持水、电解质、酸碱平衡,实现内环境的稳定,改善重要脏器功能,调节免疫系统.聚砜膜滤器目前虽广泛应用,但不可避免存在着相容不良,引发附近组织发炎,产生病变,造成溶血或凝血现象等.理想的膜滤器材料无论材料本身还是其降解产物都不能产生炎症和毒性反应,所以良好生物相容性的封堵器需进一步开发研制.     

In vitro study of the hemocompatibility of superparamagnetic contrast agent for magnetic resonance imaging

Five different nanoparticles, potentially useful in magnetic resonance imaging (MRI) after venous administration, were studied for their hemocompatibility. The in vitro methodology evaluated these materials by several parameters: cytotoxicity towards cells cultured in vitro, aggregation ability of platelets, hemolysis inducibility, intrinsic and extrinsic coagulation pathway activation, and complement activation. With the proposed clinical dose, regardless of the cell type used (murine cell line or human endothelial cells) no toxicity was observed. The presence of the particles in blood did not produce any considerable damage: either hemolysis or platelet aggregation or blood coagulation were recorded. However, a slight decrease in aggregation ability of platelets was noticed as well as an increase in partial thromboplastin time. Because of the quick removal of the particles from the bloodstream, these phenomena must be short-lived, thus avoiding significant adverse clinical effects.     

超微型光纤成像系统行离体猪肺细支气管成像

目的 探索利用超微型光纤成像系统获得离体猪肺细支气管（直径<1 mm）图像的可行性。方法 将超微型光纤成像系统的光纤（直径0.82 mm）自10具完整新鲜猪肺标本的喉部插入,连接CPAP（Continuous Positive Airway Pressure）模式无创呼吸机,观察并记录各级细支气管解剖结构、黏膜颜色、气管内分泌物等;插入到支气管远端遇到阻力时停止,固定光纤后行肺CT扫描,并行支气管三维重建,获取超微型光纤到达最远端支气管的直径。结果 超微型光纤成像系统能实时获得各级细支气管图像;三维重建图像显示超微型光纤成像系统能到达直径<1 mm的细支气管。结论 利用超微型光纤成像系统能获得离体猪肺直径<1 mm的细支气管的图像,可为获得活体肺细支气管图像提供前期动物研究基础。     

In vitro cytotoxicity and teratogenicity of norethisterone and levonorgestrel released from hollow nylon monofilaments

Direct delivery of progestogens to the uterus may be of use in the treatment of dysfunctional uterine bleeding and the sequelae of the menopause as it has the potential to overcome the problems of systemic administration. This study characterised the release of norethisterone and levonorgestrel into an aqueous medium from hollow nylon fibres with dimensions suitable for easy insertion through the post-menopausal cervix. Cell culture techniques were used to assess potential cytotoxic and teratogenic effects. The results demonstrated that the hollow fibres released norethisterone and levonorgestrel at mean rates of 0.5 and 0.6 μg/day over 14 days, respectively. There were indications, however, that both steroids were toxic to endometrial cells at concentrations of approximately 5 μg/ml, and both drugs showed signs of potential teratogenicity at 10 μg/ml. Delivery of the same doses of norethisterone using the hollow fibres reduced the effects on the endometrial and fetal cells. Delivery of levonorgestrel from the hollow fibres had no effect on the endometrial cell toxicity but potentiated the effects on the fetal cells. These results suggest that the hollow nylon fibres may be of use for the delivery of norethisterone to the uterus but that they are inappropriate for the delivery of levonorgestrel.     

In vivo safety of hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase in a large animal model for phenylketonuria

Hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase (PAL) were developed for the in vivo depletion of phenylalanine (Phe) in circulating blood. A series of experiments was conducted with a large animal model in order to explore its safety for clinical use. The level of red blood cells, white blood cells and platelets did not change during a 2-hr application of the reactors in anesthetized, heparinized dogs and monkeys with experimental hyperphenylalaninemia. No increase in blood urea nitrogen was observed due to generation of ammonia from PAL-catalyzed Phe breakdown. The other metabolic product, trans-cinnamic acid, was reported to be nontoxic. Repeated application of the PAL-reactors to the same animals did not produce untoward physiological or immunological reactions. These data suggest that PAL-reactors may be safe for in vivo use to control excess Phe brought about by fever, infection or pregnancy in phenylketonuric individuals otherwise balanced by a Phe-poor diet. Application of PAL-reactors may serve as a model for extracorporeal enzyme replacement in enzyme-deficiency diseases.     

Plasma separation using a hollow fiber membrane device

A disposable hollow fiber device was evaluated by collecting approximately 550 ml of normal donor plasma (n = 43) and by performing sham (n = 10) and therapeutic (n = 12) plasma exchanges. Blood was processed at 70 ml per min, and plasma flux averaged 23 (collection) and 25 (exchange) ml per min (mean separation efficiencies of 52 and 60%, respectively). The procedures were tolerated well by all donors and patients. The plasma hemoglobin concentration in separated plasma averaged 1 mg per dl, and cell contamination was negligible (mean of 1, 3, and 6 RBCs, platelets and WBCs/microliter, respectively). There was no evidence of in vivo classical or alternative pathway complement activation as assessed by total hemolytic complement generation (CH50), alternative pathway hemolytic activity (AP50), C3 conversion, or C5 activation, nor were unexpected changes seen in the results of laboratory tests performed after the procedure. Sieving coefficients during sham plasma exchange averaged as follows: albumin, 1.03; IgM, 1.0, IgG, 1.0; IgA, 0.98; factor V, 1.07; factor VII, 0.89; factor VIII, 1.05; and factor IX, 1.19. The device appears to be useful for separation of cell-free plasma from blood during therapeutic plasma exchange procedures.     

Flexible hollow optical fiber bundle for infrared thermal imaging

A flexible and coherent bundle of hollow optical fibers was fabricated for infrared thermal imaging. For acquisition of thermal images, differences in the transmission efficiency among the fibers were numerically compensated to obtain high temperature resolution of 1°C for measuring body temperature. In a lens system with 10-fold magnification and hollow fibers of 320-μm inner diameter, the spatial resolution is around 3 mm. The hollow-fiber bundle enables observation of the surface temperature of inner organs and blood flow of the surfaces when the bundle is introduced into the human body with an endoscope.OCIS codes: (170.3890) Medical optics instrumentation, (060.2390) Fiber optics, infrared     

Impact of spores on the comparative efficacies of five antibiotics for treatment of Bacillus anthracis in an in vitro hollow fiber pharmacodynamic model

Bacillus anthracis, the bacterium that causes anthrax, is an agent of bioterrorism. The most effective antimicrobial therapy for B. anthracis infections is unknown. An in vitro pharmacodynamic model of B. anthracis was used to compare the efficacies of simulated clinically prescribed regimens of moxifloxacin, linezolid, and meropenem with the "gold standards," doxycycline and ciprofloxacin. Treatment outcomes for isogenic spore-forming and non-spore-forming strains of B. anthracis were compared. Against spore-forming B. anthracis, ciprofloxacin, moxifloxacin, linezolid, and meropenem reduced the B. anthracis population by 4 log(10) CFU/ml over 10 days. Doxycycline reduced the population of this B. anthracis strain by 5 log(10) CFU/ml (analysis of variance [ANOVA] P = 0.01 versus other drugs). Against an isogenic non-spore-forming strain, meropenem killed the vegetative B. anthracis the fastest, followed by moxifloxacin and ciprofloxacin and then doxycycline. Linezolid offered the lowest bacterial kill rate. Heat shock studies using the spore-producing B. anthracis strain showed that with moxifloxacin, ciprofloxacin, and meropenem therapies the total population was mostly spores, while the population was primarily vegetative bacteria with linezolid and doxycycline therapies. Spores have a profound impact on the rate and extent of killing of B. anthracis. Against spore-forming B. anthracis, the five antibiotics killed the total (spore and vegetative) bacterial population at similar rates (within 1 log(10) CFU/ml of each other). However, bactericidal antibiotics killed vegetative B. anthracis faster than bacteriostatic drugs. Since only vegetative-phase B. anthracis produces the toxins that may kill the infected host, the rate and mechanism of killing of an antibiotic may determine its overall in vivo efficacy. Further studies are needed to examine this important observation.     

Flexible hollow optical fiber bundle for infrared thermal imaging

A flexible and coherent bundle of hollow optical fibers was fabricated for infrared thermal imaging. For acquisition of thermal images, differences in the transmission efficiency among the fibers were numerically compensated to obtain high temperature resolution of 1°C for measuring body temperature. In a lens system with 10-fold magnification and hollow fibers of 320-μm inner diameter, the spatial resolution is around 3 mm. The hollow-fiber bundle enables observation of the surface temperature of inner organs and blood flow of the surfaces when the bundle is introduced into the human body with an endoscope.     

In vitro and in vivo targeting of hollow gold nanoshells directed at epidermal growth factor receptor for photothermal ablation therapy

Laser-induced phototherapy is a new therapeutic use of electromagnetic radiation for cancer treatment. The use of targeted plasmonic gold nanoparticles can reduce the laser energy necessary for selective tumor cell destruction. However, the ability for targeted delivery of the currently used gold nanoparticles to tumor cells is limited. Here, we describe a new class of molecular specific photothermal coupling agents based on hollow gold nanoshells (HAuNS; average diameter, approximately 30 nm) covalently attached to monoclonal antibody directed at epidermal growth factor receptor (EGFR). The resulting anti-EGFR-HAuNS exhibited excellent colloidal stability and efficient photothermal effect in the near-infrared region. EGFR-mediated selective uptake of anti-EGFR-HAuNS in EGFR-positive A431 tumor cells but not IgG-HAuNS control was shown in vitro by imaging scattered light from the nanoshells. Irradiation of A431 cells treated with anti-EGFR-HAuNS with near-infrared laser resulted in selective destruction of these cells. In contrast, cells treated with anti-EGFR-HAuNS alone, laser alone, or IgG-HAuNS plus laser did not show observable effect on cell viability. Using 111In-labeled HAuNS, we showed that anti-EGFR-HAuNS could be delivered to EGFR-positive tumors at 6.8% ID/g, and the microscopic image of excised tumor with scattering signal from nanoshells confirmed preferential delivery to A431 tumor of anti-EGFR-HAuNS compared with IgG-HAuNS. The absence of silica core, the relatively small particle size and high tumor uptake, and the absence of cytotoxic surfactant required to stabilize other gold nanoparticles suggest that immuno-HAuNS have the potential to extend to in vivo molecular therapy.