表面矿化修饰煅烧骨/P24活性多肽仿生骨材料对MC3T3-E1细胞黏附、增殖和向成骨方向分化的影响

本研究目的是评价表面矿化修饰煅烧骨/P24活性多肽复合仿生骨材料对小鼠MC3T3-E1细胞黏附、增殖和诱导成骨分化的影响。实验分三组:A组为表面矿化修饰煅烧骨加骨形态发生蛋白-2(BMP-2)活性多肽P24修饰的复合仿生骨材料,B组为表面矿化修饰煅烧骨材料,C组为单纯的煅烧骨材料。三组材料在细胞实验前行电镜扫描观察。然后将小鼠MC3T3-E1细胞分别种植在三种材料表面,测定细胞的黏附率,MTT法检测细胞体外增殖活性,同时通过碱性磷酸酶(ALP)染色和ALP活性检测,了解小鼠MC3T3-E1细胞成骨分化情况。电镜观察显示三组材料均保留了天然的孔隙结构,孔径为200~850μm。细胞黏附率和MTT实验显示,A组MC3T3-E1细胞在材料表面的黏附性能和增殖能力明显高于B组和C组,B组则高于C组,组间差异均有统计学意义(P0.05)。ALP染色和ALP活性检测显示:A组细胞ALP活性明显高于B组和C组,B组则高于C组,组间差异均有统计学意义(P0.05)。研究表明表面矿化修饰煅烧骨/P24活性多肽仿生骨材料能促进小鼠MC3T3-E1细胞在骨基质材料表面的黏附、增殖与分化,并能较好地保持细胞的形态。     

表面修饰对羟基磷灰石异位成骨的影响

目的 了解精氨酸-甘氨酸-天冬氨酸(Arg-Gly-Asp,RGD)多肽表面修饰对羟基磷灰石(hydroxyapatite,HA)异位成骨的影响.方法 以骨髓基质干细胞(marrow stromal cells,MSCs)复合RGD多肽表面修饰的HA或单纯材料培养制备组织工程骨,将材料植入新西兰白兔脊柱旁的肌肉内,根据植入不同材料分为A、B、C和D组.A组植入MSCs复合RGD多肽表面修饰的HA培养制备的组织工程骨;B组植入MSCs复合HA培养制备的组织工程骨;C组植入RGD多肽表面修饰的HA;D组植入HA.术后4、8周取材,行组织学观察和计算机图像分析.结果 术后4、8周,各组异位成骨组织学评估,A＞B(P＜0.05),C和D组无异位成骨.结论 RGD多肽表面修饰对以HA为支架材料组织工程骨的异位成骨有明显优化作用.     

骨组织工程材料多肽修饰涂层在骨质疏松中的应用

背景：将具有特定功能的蛋白质、酶、多肽等生物活性物质固定于种植体表面,可促进骨潜能细胞及成骨细胞的增殖、分化,达到良好的成骨作用。 目的：介绍生物活性多肽精氨酸-甘氨酸-天冬氨酸的生物学特性,及其在骨质疏松状态下对细胞生物学行为和种植体骨整合的影响。 方法：计算机检索PubMed数据库(1984年1月至2013年1月)、万方数据(2002年1月至2012年12月)、CHKD期刊全文数据库(2002年1月至2012年12月)中,有关生物活性多肽精氨酸-甘氨酸-天冬氨酸的生物学特性,以及其在骨质疏松状态下对细胞生物学行为和种植体骨整合影响的文献。 结果与结论：在种植体表面接种生物活性物质可进一步改善种植体与骨组织的整合速度。通过在生物材料表面固定精氨酸-甘氨酸-天冬氨酸多肽的方法进行仿生态化学修饰,模拟体内细胞外基质环境,促进细胞黏附和生长,是早期改善内植物骨整合的有效途径,也是近年组织工程领域研究的重要方向。今后研究的重点在于设计特异高效的多肽和简单有效的固定方法,同时将对这类物质长期应用的安全性做进一步深入的研究。     

人骨髓间质干细胞与新型可降解材料生物相容性的实验研究

目的：本研究利用人骨髓间质干细胞（MSC）的增殖与分化潜能作为指标，对可降解偏磷酸钙（dCMP）材料和羟基磷灰石（HA）材料的生物相容性进行体外研究。 方法： 通过扫描电镜观察MSC在dCMP表面粘附的情况，并利用ICP和IC分析dCMP和HA的降解产物元素含量，同时采用FACS、ALP活性检测及ARS等方法对降解产物的毒性效应进行检测。 结果： dCMP对MSC的增殖有促进作用，且不影响MSC的成骨分化进程及分化后的矿化功能；而HA对MSC的成骨分化进程无影响，但对MSC的增殖和成骨分化后的矿化功能均有抑制作用。 结论： dCMP的生物相容性较HA为佳，更适合作为骨替代材料。     

合成多肽P72对葡萄球菌肠毒素超抗原抑制效应的研究

目的 观察合成多肽P72对葡萄球菌肠毒素超抗原(SEs)促人外周血单个核细胞(PBMC)增殖活性的抑制作用.方法 3H-TdR掺入法检测人 PBMC的增殖;ELISA检测IL-2、IFN-γ、TNF-β分泌情况.结果 P72对 SEA、SEB、SEC的促PBMC增殖及分泌IL-2、IFN-γ、TNF-β具有抑制作用.结论 细胞试验显示合成多肽P72对超抗原SEA、SEB、SEC的活性具有抑制作用.     

SrHA/PMMA复合骨水泥的制备、理化性能及细胞相容性研究

目的结合PMMA和锶羟基磷灰石(Sr HA)各自的优势,制备出兼具高的力学强度、合适的固化时间、较低的热释放、生物活性和骨整合性能的Sr HA/PMMA复合骨水泥,并系统性地研究Sr HA的引入对复合骨水泥的体外固化性能、力学强度和生物学性能的影响。方法将水热合成法制备的锶羟基磷灰石引入PMMA基体,制备Sr HA/PMMA复合骨水泥。系统性地对Sr HA/PMMA复合骨水泥的力学强度、固化时间、热释放、生物活性进行研究。将复合骨水泥和细胞共培养,利用MTT法、扫描电镜等研究Sr HA/PMMA复合骨水泥的细胞毒性,粘附和增殖。结果结果表明,与纯的PMMA骨水泥(对照组)相比,Sr HA/PMMA复合骨水泥的固化热释放明显降低(约80~84℃),同时又维持了合适的固化时间(8~11分钟)和较好的力学性能(抗压强度为90MPa左右)。Sr HA的引入,不仅赋予了复合骨水泥生物活性,也显著地改善了其细胞/材料的相互作用。浸泡在SBF后,Sr HA/PMMA复合骨水泥显示出更好的体外矿化性能。与成骨细胞MC3T3-E1共培养后,表面沉积的羟基磷灰石能够更好的促进细胞的粘附和爬行。结论兼具优异的理化性能和生物活性的Sr HA/PMMA复合骨水泥,有着广阔的骨科微创修复应用前景。     

表面修饰对羟基磷灰石修复骨缺损的影响

精氨酸-甘氨酸-天冬氨酸（Arg-Gly-Asp,RGD）多肽是介导种子细胞与支架材料黏附的多肽链．RGD序列可被固有黏附蛋白受体特异性结合．在生物材料表面自发形成一分子层．为与受体介导的种子细胞提供特异性位点而促进细胞的黏附和分化。笔者旨在应用RGD多肽对羟基磷灰石（hydroxyapatite．HA）材料进行表面修饰处理．以促进骨髓基质干细胞（marrow stromal cells．MSC）在其表面的黏附和生长．为骨组织工程提供一种支架材料的表面修饰手段。     

纳米相复合材料β-磷酸三钙/胶原的细胞相容性研究

目的 探索和研究新型纳米相β-磷酸三钙，胶原纤维复合材料（nano-sized β-TCP／CF）的细胞相容性，为纳米活性复合材料在临床和组织工程上的应用提供理论和实验基础。方法 用湿化学处理的方法制备新型纳米相阻磷酸三钙／胶原纤维复合材料，并通过X线衍射和扫描电镜对其进行表征。以建立的成骨样细胞MG63细胞株，与纳米复合材料在体外培养体系复合培养，并以单纯的非纳米结构β-磷酸三钙和不加材料的空白作为阳、阴性对照，采用MTT法、扫描电镜及碱性磷酸酶活性检测，观察细胞的黏附、增殖以及在材料表面的形态和对细胞的代谢作用。结果 纳米β-磷酸三钙，胶原纤维复合材料上的细胞黏附数、增殖的数量，在材料表面的分布均优于非纳米β-磷酸三钙（P〈0．05）；和空白对照相比，无显著性差异（P〉0．05）；碱性磷酸酶的活性在1d、3d、5d虽无明显差异，从第7d始，却明显优于非纳米相β-磷酸三钙。结论本研究显示，纳米相β-磷酸三钙，胶原纤维复合材料与单纯非纳米β-磷酸三钙相比，更能促进成骨样细胞的黏附、增殖及其功能代谢，表明其对成骨样细胞具有良好的细胞相容性，可以成为一种新型的具有应用前途的骨修复或组织工程材料。     

表面矿化修饰煅烧骨/BMP2活性多肽复合MC3T3-E1细胞构建组织工程骨

探讨表面矿化修饰煅烧骨/BMP₂活性多肽复合材料、表面矿化修饰煅烧骨和单纯煅烧骨复合MC3T3-E1细胞构建的组织工程骨在体内的成骨能力。实验分3组,A组：表面矿化修饰煅烧骨/BMP₂活性多肽复合材料,B组：表面矿化修饰煅烧骨,C组：单纯煅烧骨。诱导培养MC3T3-E1细胞,将其分别接种于3组材料,倒置相差显微镜和环境扫描电镜分别观察细胞生长情况。将18只新西兰大白兔随机分成3组,每只大白兔作两侧骶棘肌肌袋模型,然后将3组材料分别植入大白兔骶棘肌内,分别于术后第4、8周各组处死大白兔3只,行组织学观察及新生骨面积测定。通过观察发现MC3T3-E1细胞在3组材料表面生长良好,表面矿化修饰煅烧骨/BMP₂活性多肽复合材料能促进MC3T3-E1细胞在其表面粘附与增殖并能较好地保持细胞的形态。术后第4、8周组织学观察A组材料新生骨明显多于B组,B组多于C组。术后4周和8周新生骨面积测定值A、B、C组分别为（19 712.524±3 782.126）μm²、（28 227.617±2 455.375）μm²,（11 648.507±1 047.221）μm²、（14 592.892±899.532）μm²,（7 986.655±903.487）μm²,（11 254.822±669.508）μm²。表面矿化修饰煅烧骨/BMP₂活性多肽复合材料是一种较理想的骨组织工程复合材料,有望应用于临床。     

IGF—1和胰岛素对成骨细胞功能影响的研究进展

胰岛素样生长因子—1(IGF—1)是一类既具有促进细胞分化和增殖活性又具有胰岛素样作用的多肽。IGF—1与胰岛素原有60％的结构同源性，对小鼠、大鼠和人的成骨细胞的研究结果显示：IGF—1和胰岛素可通过促进骨祖细胞及成骨样细胞的增殖和分化等多种机制而发挥保护骨量的作用，IGF—1和胰岛素的作用受IGF结合蛋白(IGFBP)、激素和细胞因子的调节。     

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.     

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.     

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.     

'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.     

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.     

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.     

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.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.