壳聚糖微球包裹幽门螺杆菌全菌蛋白抗原的制备及体外释放性能（英文）

背景:包裹幽门螺杆菌全菌蛋白抗原的研究仍处于探索阶段,有关壳聚糖微球包裹幽门螺杆菌全菌蛋白抗原的制备工艺及体外释放性能的文献甚少。目的:探讨幽门螺杆菌全菌蛋白抗原壳聚糖微球的制备工艺及体外释放特性。方法:采用沉淀法制备壳聚糖微球,筛选最佳制备工艺及配比、包裹时间,并在电镜下观察微球的形态和粒径。采用壳聚糖微球包裹幽门螺杆菌全菌蛋白抗原,BCA法测定幽门螺杆菌全菌蛋白抗原微球的包裹率、包裹量及体外释放率。结果与结论:终体积分数为1%的冰醋酸、硫酸钠为交联剂、pH 5.0、滴加交联剂时不粉碎处理为壳聚糖微球最佳制备工艺,电镜观察显示微球表面光滑、形态圆整,具有良好的分散性,多数微球粒径为1.0-5.0μm。幽门螺杆菌全菌蛋白抗原微球的包裹率为80.4%,包裹量为16.4%,48 h总释放率为19.4%,幽门螺杆菌全菌蛋白抗原微球整体呈缓慢释放状态。结果证实,实验制备的壳聚糖微球对幽门螺样菌全菌蛋白抗原具有良好的包裹率和包裹量,幽门螺杆菌全菌蛋白抗原微球整体呈缓慢释放状态。     

幽门螺杆菌全菌蛋白抗原壳聚糖微球体外释放特性

背景：不同方法制备出的幽门螺杆菌全菌蛋白抗原壳聚糖微球,其包裹率和控释效果也不同。 目的：探讨幽门螺杆菌全菌蛋白抗原壳聚糖微球的最佳制备方案,观察其体外释放特性。 方法：使用Berthold沉淀法制备壳聚糖微球,筛选最佳制备方案;使用扫描电镜及粒径分析仪观察壳聚糖微球的形态及粒径分布;冻干后的壳聚糖微球包裹幽门螺杆菌全菌蛋白抗原,使用BCA蛋白定量试剂盒测量分析微球的抗原包裹率、包裹量及释放率。 结果与结论：从32种壳聚糖微球制备方案中筛选出了以海得贝壳聚糖为原料、冰乙酸的浓度为1%、硫酸钠为沉淀剂、pH值为5.0、不进行超声处理方案为最佳制备方案,扫描电镜示微球光滑圆整、致密,粒径分布在1.0~5.0 μm;抗原包裹率为79.92%,包裹量为16.47%;体外释放实验表明,总抗原释放率为20.39%,呈缓慢释放状态。     

制备壳聚糖微球体外缓释TGF-β_1的研究

应用离子交联沉淀法制备壳聚糖-转化生长因子（TGF-β1）缓释微球,研究其体外缓释性能。采用离子交联沉淀法制备壳聚糖微球,以其包裹TGF-β1,制备具有缓释效能的壳聚糖-TGF-β1缓释微球。用扫描电镜、激光粒度分析仪、Elisa法等观察其表面形态,测定药物载药率、包封率、体外缓释效率等指标。结果表明：所得微球球形良好,表面光滑,粒径分布集中,平均粒径272nm。壳聚糖微球有较高的药物包封率,达80.60%。体外释放试验提示,TGF-β1初期存在突释现象,前24h释放达27%,但其后可从壳聚糖微球中稳定释放,7d累计释放达41%。离子交联沉淀法制备壳聚糖缓释微球方法简单易行,所得壳聚糖-TGF-β1微球具有良好的缓释效能,提示其在组织工程领域具有良好的应用前景。     

制备壳聚糖微球体外缓释TGF-β1的研究

应用离子交联沉淀法制备壳聚糖-转化生长因子（TGF-β1）缓释微球,研究其体外缓释性能。采用离子交联沉淀法制备壳聚糖微球,以其包裹TGF-β1,制备具有缓释效能的壳聚糖-TGF-β1缓释微球。用扫描电镜、激光粒度分析仪、Elisa法等观察其表面形态,测定药物载药率、包封率、体外缓释效率等指标。结果表明：所得微球球形良好,表面光滑,粒径分布集中,平均粒径272nm。壳聚糖微球有较高的药物包封率,达80.60%。体外释放试验提示,TGF-β1初期存在突释现象,前24h释放达27%,但其后可从壳聚糖微球中稳定释放,7d累计释放达41%。离子交联沉淀法制备壳聚糖缓释微球方法简单易行,所得壳聚糖-TGF-β1微球具有良好的缓释效能,提示其在组织工程领域具有良好的应用前景。     

成骨生长肽壳聚糖-海藻酸钠微球的制备及体外检测

背景：成骨生长肽体外注射可以刺激外周血和骨髓细胞数增加,增加动物的骨量,加速骨折愈合,但因多肽不稳定性及注射应用不方便,限制了其临床应用。 目的：应用乳化交联法制备成骨生长肽壳聚糖-海藻酸钠缓释微球,并对其粒径、载药、体外释药、理化特性进行检测。 方法：以戊二醛作为交联剂,应用乳化交联法制备具有控制释放功能的负载成骨生长肽壳聚糖-海藻酸钠微球,显微镜及扫描电镜观察微球的形态和粒径;利用酶联免疫吸附实验动态检测成骨生长肽壳聚糖-海藻酸钠微球的载药率、包封率和缓释规律。 结果与结论：乳化交联法制备的壳聚糖-海藻酸钠微球,球形良好,球体表面有较多微孔,具有较高的包封率(>72%)。体外药物释放实验表明,成骨生长肽可以从壳聚糖-海藻酸钠微球中缓慢释放,整个释放过程可达49 d,累积释放率>85%。提示应用乳化交联法制备的负载成骨生长肽壳聚糖-海藻酸钠缓释微球,具有很好的控制释放成骨生长肽的能力。     

喷雾干燥法制备眼用壳聚糖/明胶复合微球**

背景：普通滴眼液由于泪液冲刷与鼻泪管吸收等因素,在眼表停留时间短,生物利用度低。 目的：以壳聚糖、明胶为载体材料,左氧氟沙星为模型药物,制备应用于眼表的缓控释微球并考察其理化性质与体外释放。 方法：采用喷雾干燥法制备左氧氟沙星壳聚糖/明胶微球,通过扫描电镜观察微球的表面形态,激光粒度仪测量微球粒径分布与zeta电位,高效液相色谱法检测微球的载药率与包封率,动态透析法研究微球体外药物释放情况。 结果与结论：所得微球形态良好,粒径分布窄,平均粒径为(1 267.4±115.3) nm,zeta电位为+(32.19±0.85) mV,载药量为(18.31±0.22)%,包封率为(91.53±1.12)%。载药微球体外释放符合一级释药方程Ln(1-Q)=-0.699 1t-0.086 4,r2=0.945 1。说明壳聚糖/明胶载药微球对左氧氟沙星具有缓释作用。实验采用喷雾干燥法成功制备了粒径及分布适宜、释放周期较理想、药物稳定性好的载左氧氟沙星壳聚糖明胶缓释微球。      

BSA-PLGA缓释微球的制备及优化条件的探索

目的以牛血清白蛋白(BSA)为模型蛋白、聚乳酸-聚乙二醇酸(PLGA)为包裹材料,探索微球的制备方法并优化制备工艺。方法采用复乳-溶剂挥发法制备BSA-PLGA微球,显微测量微球粒径,以微量BCA法测定微球的蛋白含量并计算包封率,进行体外释放,测定微球的累积释放量。探索BSA投药量、PLGA用量、PVA浓度、超声功率等因素对微球包封率、突释量的影响。结果通过正交实验设计,优化了微球的制备工艺,其优化条件是BSA投药量为10mg、PLGA用量为250mg、PVA浓度为1.5%、超声乳化功率为60周。结论通过控制不同的因素,可以得到较高包封率、较小突释、适当载药量和粒径的BSA-PLGA微球。     

重组人骨形态发生蛋白2壳聚糖纳米微球的制备及体外细胞毒性

背景：通过各种微球负载骨生长因子使骨形态发生蛋白达到缓释效果逐渐成为研究热点,但关于载药壳聚糖纳米微球的生物相容性特别是细胞毒性的报道较少。 目的：对重组人骨形态发生蛋白2壳聚糖纳米微球进行细胞毒性检测,评估应用壳聚糖纳米微球作为重组人骨形态发生蛋白2缓释载体的生物安全性。 方法：通过离子交联法制备空白壳聚糖纳米微球,应用透视电镜观察微球的形态,激光粒径分析其粒径分布;通过重组人骨形态发生蛋白2壳聚糖纳米微球体外细胞毒性试验评估微球的生物安全性。 结果与结论：离子交联法制备的壳聚糖微球,球形规整,分散均匀,微球平均粒径为230 nm,分布较集中。载药及空白微球的反应分级为0或1级,均为合格。提示,离子交联法制备可成功制备出负载重组人骨形态发生蛋2的纳米微球,且微球细胞毒性检测合格,为进一步的骨组织工程研究提供理论实验基础。     

利福平/聚乳酸-聚羟基乙酸缓释微球的制备及特性

背景：虽然国内外有很多制备利福平/聚乳酸-聚羟基乙酸共聚物(poly lactic acid-glycolic acid copolymer,PLGA)微球的报道,但这些微球粒径多在10 μm左右,不适合与磷酸钙骨水泥复合制备成具有良好降解性的抗结核修复材料。 目的：制备大粒径利福平/PLGA缓释微球,观察其理化特性和体外缓释特性。 方法：以PLGA为载体,将利福平分散于PLGA的有机溶剂中,采用复乳溶剂挥发法制备利福平/ PLGA缓释微球。光镜和扫描电镜下观察微球的形态特征,测定微球平均直径和跨距,高效液相色谱法测定载药量和包封率,以溶出法和高效液相色谱法观察其体外释药特性,并拟合药物体外释放曲线建立曲线方程。 结果与结论：利福平/PLGA微球电镜观察呈圆球形,分散性好,粘连少,粒径分布集中,平均粒径(80.0±9.4) μm。载药量、包封率分别为(33.18±1.36)%,(54.79±1.13)%。体外缓释试验显示突释期内微球释放度为(14.66±0.18)%,前3 d累计释放度(18.09±0.45)%,到42 d体外累积释放度达到(92.17±1.23)%。提示利福平/PLGA微球具有良好的缓释效果,是一种较为理想的抗结核药物的载体材料和释放系统;PLGA是良好的药物缓释载体,可以用来制备载药缓释微球。     

抗凝血纳米壳聚糖微球的合成、表征及生物安全性评价

 背景：有研究显示,壳聚糖等天然多糖经磺化改性后具有类似肝素的抗凝功能,因磺酸化后的壳聚糖其形成的磺酸根基团与肝素的活性基团相似,具有良好的抗凝血性。 目的：制备具有抗凝血功能的纳米壳聚糖微球,检测其形态结构、理化性能及生物安全性。 方法：利用乳相法合成纳米壳聚糖微球,通过磺化反应合成磺酸化壳聚糖微球,通过透射电镜描述其形态特征,红外光谱观察其特异基团峰值变化。①凝血实验：分别将肝素、纳米壳聚糖微球及10,30,50 mg磺酸化壳聚糖微球加入SD大鼠血中,检测凝血指标。②溶血实验：分别将去离子水、生理盐水及10,30,50 g/L磺酸化壳聚糖微球浸提液加入兔2%红细胞悬液中,检测溶血率。③细胞毒性实验：分别采用含体积分数10%胎牛血清的DMEM培养基及10,30,50 g/L磺酸化壳聚糖微球的浸提液培养人脐静脉血管内皮细胞,72 h后检测细胞相对增殖率及毒性分级。 结果与结论：扫描电镜显示磺酸化壳聚糖微球具有良好的形态结构,粒径大小50 nm,红外图谱提示存在磺化取代。体外凝血实验表明磺酸化壳聚糖微球具有显著抗凝血作用,抗凝血效果呈剂量效应关系。磺酸化壳聚糖微球符合国标关于溶血率小于5%的安全标准,无致溶血性。细胞毒性实验表明磺酸化壳聚糖微球浸提液无明显细胞毒性,其生物安全性符合国家标准。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.