5000/壳聚糖水凝胶微球模板的载肝素层层自组装微胶囊

静电层层自组装是微胶囊载药简单有效的方法。本文采用硫酸钠沉淀的方法制备了具有正电荷的壳聚糖微球模板,通过层层自组装的方法装载抗凝血药物肝素。壳聚糖（CS）作为聚阳离子和肝素作为聚阴离子,在壳聚糖微球的模板上层层自组装形成{CS/Hep}3。{CS/Hep}3包被壳聚糖微球模板的微胶囊通过荧光倒置显微镜、激光共聚焦显微镜和激光粒度分析进行了表征。壳聚糖和肝素的层层自组装过程通过Zeta电位分析进行了监测。结果表明{CS/Hep}3包被壳聚糖微球模板的微胶囊平均直径1μm,包封率和载肝素量分别为83.8%和3.05%。     

经颅多普勒超声监护下超声微泡剂对尿激酶溶栓治疗作用的影响

目的 评价经颅多普勒超声(TCD)监护下超声微泡剂辅助尿激酶溶栓治疗的有效性. 方法 将雄性新西兰大白兔32只按随机数字表法分为单用尿激酶组和尿激酶联合超声微泡剂组,每组各16只.采用兔颈外动脉插管注入自体血栓方法制备成大脑中动脉栓塞模型,并应用TCD监测血栓溶解过程.尿激酶联合超声微泡剂组静注尿激酶后立即静注六氟化硫超声微泡剂(声诺维).2组动物均在溶栓治疗后2h内持续TCD监测并记录溶栓治疗后不同时间点大脑中动脉血流动力学变化,并根据TCD频谱形态及血流速度判断血管再通情况. 结果 2组动物溶栓治疗前大脑中动脉的平均血流速度比较差异无统计学意义(P＞0.05).溶栓治疗后单用尿激酶组完全再通l例,部分再通4例,血管再通率为31.3％;尿激酶联合超声微泡剂组完全再通3例,部分再通6例,血管再通率为56.3％.2组动物病理检查均未见脑出血.单用尿激酶组梗死灶大小占梗死半球的百分率平均为13.9％,尿激酶联合超声微泡剂组梗死灶大小占梗死半球的百分率平均为9.1％,比较差异有统计学意义(P=0.025). 结论 TCD监测下应用超声微泡剂有助于增强尿激酶的溶栓治疗效果,初步证明TCD联合超声微泡剂可辅助尿激酶溶栓治疗脑梗死.     

壳聚糖-肝素静电自组装多层膜在钛表面进行的生物化修饰**

摘要 背景：基于聚电解质阴阳离子交替组装的静电自组装技术可在温和、简单、易控的条件下实现多种生物大分子在材料表面的固定,已成为生物材料表面设计的重要手段。 目的：利用静电自组装技术将具有生物活性的壳聚糖和肝素固定在钛表面,实现钛表面的氨基多糖生物化修饰,构建一种钛种植体材料的新型生物化表面,以改善钛的细胞相容性。 方法：首先采用NaOH处理钛基材,获得多孔、负电荷的钛表面;然后吸附一层正电荷的聚赖氨酸;最后,多次交替吸附负电荷的肝素和正电荷的壳聚糖,形成以壳聚糖为最外层的多层膜结构。通过漫反射红外光谱扫描电镜和原子力显微镜对多层膜进行表征。并与成骨细胞共培养,观察成骨细胞的黏附、增殖以及分化情况。 结果与结论：红外光谱、原子力显微镜、扫描电镜结果表明肝素-壳聚糖多层膜逐渐形成。此涂层可促进成骨细胞的黏附、增殖和分化。肝素-壳聚糖多层膜有望成为一种新型的生物化钛表面,从而改善钛表面的生物相容性。 关键词：静电自组装;钛;表面改性;壳聚糖;肝素 doi:10.3969/j.issn.1673-8225.2010.21.008     

静电贴附海藻酸钙微球制备自组装支架

背景：微球型注射支架在软骨组织工程中具有良好的发展前景,但是常存在体内成型困难和微球游走等问题。 目的：探讨利用静电作用力将负电性海藻酸钙微球与正电性壳聚糖微球贴附在一起制备自组装支架的可行性。 方法：用乳化内部凝胶法制备表面带负电荷的海藻酸钙微球,用喷雾干燥法制备表面带正电荷的壳聚糖微球。扫描电镜观察微球的表面形貌、光学显微镜分析微球的粒径及其粒径分布,zeta电位仪测定微球的表面电位;将两种带电荷微球的悬浮液混合在一起制备自组装支架,用光学显微镜和扫描电镜观察微球间的静电贴附情况,并对支架的压缩弹性模量进行了分析。 结果与结论：海藻酸钙微球的平均粒径为52.5 μm,表面电位为-23.5 mV,壳聚糖微球的平均粒径为4.1 μm,表面电位为+9.8 mV,两种微球表面光滑,成球性良好;光学显微镜和扫描电镜下可以观察到小粒径的壳聚糖微球能够将海藻酸钙微球贴附在一起,支架的压缩弹性模量随微球固含量的增加而增加,随溶液离子强度的增加而减小,随壳聚糖微球与海藻酸钙微球质量比的增加,先增加后减小,当壳聚糖微球与海藻酸钙微球质量比为2∶1时支架的压缩弹性模量最佳。提示正电性的壳聚糖微球可将负电性的海藻酸钙微球贴附在一起而形成自组装型支架。 关键词：静电作用;海藻酸钙;壳聚糖;贴附;自组装 doi:10.3969/j.issn.1673-8225.2010.03.013     

高分子材料超声对比剂的制备及显影特征

摘要 背景：目前所用的超声对比剂均为内含不同气体成分的微气泡,其外壳材料多数为表面活性剂类、人血蛋白质类、脂类等。随着高分子化学的发展,高分子材料对比剂成为超声对比剂研究领域的热点。 目的：探讨各种超声对比剂制备中遇到的困难以及解决方法,从而最终寻找合理的高分子材料超声对比剂。 方法：采用电子检索的方式,在万方数据库(http://www.wanfangdata.com.cn/)中检索2005-01/2010-12有关高分子材料应用于超声造影方面的研究文章,关键词为“高分子材料,超声,对比剂”。排除重复研究、普通综述或Meta分析类文章,筛选纳入26篇文献进行评价。 结果与结论：近年来随着高分子科学与多学科融合的分子医学的兴起和快速发展,显像对比剂受到了越来越广泛的关注。高分子材料超声对比剂由于具有好的生物相容性,粒径大小均匀,良好的抗压性能,较长的显影持续时间等特点,已成为目前研究的热点。其中靶向微泡对比剂经静脉注射可到达特定靶区,低功率超声作用下可提高局部组织显影的分辨率。携带治疗药物或基因的靶向微泡对比剂在低频(1 MHz)超声作用下可以产生瞬态空化效应,迫使细胞膜的通透性增加,从而有效提高了药物或基因的转染率。如今,靶向微泡携抗肿瘤药物联合超声作用正逐渐成为治疗肿瘤的一种新模式,是近期医学研究的一个热点。超声联合靶向微泡技术在临床诊断和治疗中显示出了较大的优势,但其准确的生物学机制目前医学界还未清楚,超声治疗参数需进一步优化。 关键词：高分子材料;超声;对比剂;微泡;靶向 doi:10.3969/j.issn.1673-8225.2011.16.024     

低功率聚焦超声联合微泡对兔血脑屏障通透性影响的实验研究

目的 研究低功率聚焦超声联合微泡靶向开放兔血脑屏障(BBB)后其通透性变化规律.方法 MRI引导下,静脉注射微泡,聚焦超声照射兔大脑一侧靶点,对侧镜像点为对照组,未处理者为健康组.照射后即刻、2 h、4 h、6 h、8h、24 h、1周分别行MRI增强扫描测定信号强度值;荧光分光光度法榆测兔脑组织伊文思蓝量(EB).结果 超声照射后BBB即刻开放,2 h MRI信号增强值和脑组织EB量达到峰值,8 h后恢复正常.靶点MRI信号增强值与脑组织EB含量的相关系数r=0.9154.结论 MRI引导下聚焦超声联合微泡能靶向可逆地开放BBB,MRI信号增强值在一定程度上可反映BBB的开放状况.     

超声辐射微泡增效骨髓间充质干细胞移植治疗心肌梗死

背景：超声辐射微泡已被大量应用于临床心肌微循环诊断,其安全性已得到证实。研究显示超声靶向破坏微泡可以使骨骼肌毛细血管破坏和局部红细胞渗出,可以促进细胞穿过内皮生理屏障。 目的：探讨超声辐射微泡是否可以增加骨髓间充质干细胞移植治疗心肌梗死的效果。 设计、时间及地点：随机对照动物观察,于2006-10/2008-05在东南大学医学院完成。 材料：2月龄中国家猪20只,随机分为超声微泡组12只,细胞对照组8只。超声微泡对比剂SonoVue,国药准字J20030117,为上海博莱信谊药业有限责任公司产品。 方法：无菌条件下抽取猪骨髓液,密度梯度离心法分离纯化骨髓间充质干细胞。两组动物均建立急性心肌梗死模型,造模后14 d,超声微泡组通过OTW球囊导管先把2.4 mL超声微泡对比剂SonoVue经冠状动脉注入左前降支中段,同时在体表给予1 MHz,2 W/cm2超声辐射心肌梗死区,连续辐射90 s后,再注入超顺磁性氧化铁标记的骨髓间充质干细胞5×106个;细胞对照组同法仅单纯输注骨髓间充质干细胞。 主要观察指标：采用64层螺旋CT检查心功能变化,光镜观察心肌组织学检测结果,电镜观察血管内皮细胞超微结构。 结果：与移植前1 d比较,移植后6周两组左心室射血分数均明显增加,且超声微泡组增加幅度高于细胞对照组(P < 0.01)。与细胞对照组比较,超声微泡组普鲁士蓝阳性细胞数明显增多(P < 0.01),且多数分布于心肌梗死周边区,有2例标本可见普鲁士蓝阳性细胞分化为新生血管内皮细胞;梗死周边区毛细血管密度明显升高(P < 0.05)。两组心肌血管内皮细胞超微结构无差异,但移植后0 h超声微泡组可见血管内皮间隙增宽。 结论：超声辐射微泡可促进梗死心肌内猪自体骨髓间充质干细胞的移植,促进心肌血管新生,从而改善因心肌梗死而受损的心功能。     

小波变换在量子点编码识别中的应用*☆

背景：为实现更多种类的量子点编码,量子点的荧光发射峰必定出现重叠,这就造成了量子点编码识别的困难。 目的：应用小波变换对重叠峰展开技术,对两种相邻波长量子点的编码进行识别。 方法：在显微镜引导下,以375 nm的紫外光激发单个量子点编码微球的荧光光谱,被光纤光谱仪采后,应用小波变换对数据多维展开,然后经过样条函数处理,再通过小波反变换重构波谱展开的光谱。 结果与结论：为了使处理数据的长度为2n,在原始数据进行了插值运算。经过小波变换处理后,峰位置保持不变,能够提取编码荧光光谱的特征值。通过小波变换,混合微球的荧光光谱被展开,能够识别出两种量子点编码,提高了识别的分辨率。通过提高对相邻光谱的编码的识别,量子点编码的颜色必将增加,从而显著丰富编码的信息量。结果提示用小波变换对光谱进行处理后,可以实现对不同波长的荧光展开,提高了识别效率,为实现肿瘤标志物的高通量检测奠定基础。     

超声造影剂在颅脑疾病中应用的现状与展望

近年来,有关超声造影剂的研究日益增多,而其在颅脑疾病方面应用相对较少。超声造影剂结合彩色多普勒技术有助于急性血栓和陈旧性血栓的鉴别,提高脑动静脉畸形的检出率;将溶栓药物整合于造影剂微泡中,同时将高度特异的抗体或配体连接于微泡表面注入体内,配合超声的局部照射可显著增强溶栓效果,并能减轻药物的不良反应。新的造影剂可同时用于诊断和治疗,即在血栓成像后进行溶栓治疗。     

颈动脉狭窄超声检查的应用及进展

超声检查无创,简单易行,实时成像,直观,重复性好,已成为颈动脉疾病首选的检查方法,并能够术前评价颈动脉狭窄治疗方案及疗效。随着超声技术的不断发展,颈动脉超声造影、血管内超声、术中超声、三维及四维血管超声已在临床发挥着重要作用。近年来,彩色多普勒超声已从形态学成像向功能成像发展,为临床提供更丰富的信息并指导治疗。目前,超声血管成形术以及超声造影剂微泡的空化效应已将超声从诊断推向治疗。本文对颈动脉超声检查的在颈动脉狭窄诊断上的应用及进展进行综述。     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.