骨靶向抗肿瘤药物中间体N-Boc-N’-3,3-双(二乙氧膦酰基)丙基甘氨酰胺的合成

采用缩合、Michael加成、氢化还原和偶联等多步应合成了骨靶向抗肿瘤药物的关键中间体——N-Boc-N’-3,3-双(二乙氧膦酰基)丙基甘氨酰胺,其结构经1H NMR,13C NMR,IR和MS确证。     

大豆异黄酮对骨质疏松模型大鼠骨量及微观结构的影响

为研究大豆异黄酮（SI）对骨质疏松模型大鼠骨量及微观结构的影响,将46只雌性SD大鼠双侧摘除卵巢,术后一周按血清总胆固醇水平随机分为5组,分别给予雌激素,低、中、高剂量SI干预并设正常对照组,实验周期为12周,灌胃给药,每周称质量一次,分别在去卵巢、给药4、8周处死时抽取尾静脉血,实验结束后分别测定血清碱性磷酸酶（AKP）活性及骨密度等指标。结果表明,高剂量SI干预对维持大鼠骨密度的作用与雌激素相似,去卵巢后干预SI可提高碱性磷酸酶（AKP）活性并能缓解因去卵巢造成的骨丢失,全视野下骨形态学以雌激素组、高剂量SI干预组与正常组结构最为接近。提示大豆异黄酮对骨质疏松模型大鼠的骨量及微观结构存在一定影响,中、高剂量干预可使骨质疏松模型大鼠血清AKP酶活性增加、逆转因去势造成的骨密度下降,考虑到植物雌激素与哺乳动物的雌激素受体（ER）结合能力低下,采用SI在临床开展干预的剂量与远期效果尚待进一步论证。     

Raman spectroscopy reveals differences in collagen secondary structure which relate to the levels of mineralisation in bones that have evolved for different functions

Bone is a composite material comprising a collagen fibril scaffold surrounded by crystals of carbonated‐hydroxyapatite mineral. It is well established that the relative proportions of mineral and collagen in mature bone are not definite and are adapted in order to ‘tune’ its mechanical properties. It is not known, however, how the mineral to collagen ratio is controlled. This paper uses Raman spectroscopy (which permits the probing of both the mineral and the collagen phases of bone) to explore the hypothesis that the control mechanism is related to the nature of the collagen and that bones with different levels of mineralisation have qualitatively different collagen. Raman spectra of functionally adapted bones with varying levels of mineralisation are presented and features that indicate the differences in the collagen's secondary structure (amide I band profiles) and post‐translational modification (hydroxyproline/proline ratios) are highlighted. The study demonstrates that Raman spectroscopy can provide a means to investigate the mechanisms that control the mineral to collagen ratio of bone. Understanding these mechanisms could pave the way towards the therapeutic alteration of the mineral to collagen ratio and, thus, the control of the mechanical properties of bone. Copyright © 2012 John Wiley & Sons, Ltd.     

Age- and direction-related adaptations of lumbar vertebral trabecular bone with respect to apparent stiffness and tissue level stress distribution

The objective of this study was to study the age-related adaptation of lumbar vertebral trabecular bone at the apparent level, as well as the tissue level in three orthogonal directions. Ninety trabecular specimens were obtained from six normal L4 vertebral bodies of six male cadavers in two age groups, three aged 62 years and three aged 69 years, and were scanned using a high-resolution micro-computed tomography （micro-CT） system, then converted to micro- finite element models to do micro-finite element analyses. The relationship between apparent stiffness and bone volume fraction, and the tissue level yon Mises stress distribution for each trabecular specimen when compressed separately in the longitudinal direction, medial-lateral and anterior-posterior directions （transverse directions） were derived and compared between two age groups. The results showed that at the apparent level, trabecular bones from 69-year group had stiffer bone structure relative to their volume fractions in all three directions, and in both age groups, changes in bone volume fraction could explain more variations in apparent stiffness in the longitudinal direction than the transverse directions; at the tissue level, aging had little effect on the tissue von Mises stress distributions for the compressions in all the three directions. The novelty of the present study was that it provided quantitative assessments on the age and direction- related adaptation of Chinese male lumbar vertebral trabecular bone from two different levels： stiffness at the apparent level and stress distribution at the tissue level. It may help to understand the failure mechanisms and fracture risks of vertebral body associated with aging and direction for the prevention of fracture risks in elder individuals.     

发钙与骨密度两种测试方法的观察比较

探讨了发钙检测的可靠性。对同一个患者同时做两种检测,发钙用ICPQ－1012型电感耦合高频等离子体发射光谱仪检测,骨密度则采有中国科学技术大学中佳光电仪器分公司生产的GBD－928骨密度测试检测,均由专人进行操作。结果表明,151例患者的发钙与骨密度测试结果相符的有74例,占49％。可见评价一个人的钙营养状况不能只看发钙,特别对发钙高的患者,应结合临床,最好再做骨密度或甲状旁腺素等的检测,以便准确地判断体内钙营养状况。     

利骨素抗去卵巢大鼠骨矿物元素代谢紊乱的作用机制

通过测定骨元素含量和血清相关激素及白细胞介素-6水平,探讨了利骨素对去卵巢大鼠骨元素代谢的影响及其机制。将健康4月龄雌性SD大鼠24只随机分成3组:A组,假去卵巢组;B组,去卵巢组;C组,去卵巢+利骨素组。结果表明,去卵巢大鼠骨Ca、Mg、S、Mn、Zn等含量显著降低,P含量显著增加;应用利骨素可使去卵巢大鼠降低的骨Ca、Mg、S、Mn、Zn等含量显著回升,P含量显著回降。血清相关激素:去卵巢组较假去卵巢组大鼠,血清雌二醇(E2)、孕酮(P)、促甲状腺激素(TSH)、甲状腺素(T4)、降钙素(CT)、皮质醇(Cortisol)、生长素(GH)等含量降低,卵泡刺激素(FSH)、黄体生成素(LH)、白细胞介素-6(IL-6)等含量升高;去卵巢+利骨素组较去卵巢组,血清P,GH,Cortisol,TSH,T4等含量回升,LH含量回降。提示利骨素改变去卵巢大鼠体内相关激素水平是其纠正去卵巢大鼠骨元素代谢紊乱作用的重要机制。     

Composites of poly(L‐lactide‐trimethylene carbonate‐glycolide) and surface modified SBA‐15 as bone repair material

This work aims to develop novel composites from a poly(L ‐lactide‐co‐trimethylene carbonate‐co‐glycolide) (PLTG) terpolymer and mesoporous silica (SBA‐15) nanofillers surface modified by post‐synthetic functionalization. SBA‐15 first reacts with a silane coupling agent, γ‐aminopropyl‐trimethoxysilane to introduce ammonium group. PLLA chains were then grafted on the surface of SBA‐15 through ammonium initiated ring‐opening polymerization of L ‐lactide. Composites were prepared via solution mixing of PLTG terpolymer and surface modified SBA‐15. The structures and properties of pure SBA‐15, γ‐aminopropyl‐trimethoxysilane modified SBA‐15 (H₂N‐SBA‐15), PLLA modified SBA‐15 (PLLA‐NH‐SBA‐15), and PLTG/PLLA‐NH‐SBA‐15 composites were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, X‐ray diffraction, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, transmission electron microscopy, N₂ adsorption‐desorption, differential scanning calorimetry, contact angle measurement, and mechanical testing. The results demonstrated that PLLA chains were successfully grafted onto the surface of SBA‐15 with grafting amounts up to 16 wt.%. The PLTG/PLLA‐NH‐SBA‐15 composites exhibit good mechanical properties. The tensile strength, Young's modulus, and elongation at break of the composite containing 5 wt.% of PLLA‐NH‐SBA‐15 were 39.9 MPa, 1.3 GPa, and 273.6%, respectively, which were all higher than those of neat PLTG or of the composite containing 5 wt.% of pure SBA‐15. Cytocompatibility tests showed that the composites present very low cytotoxicity.     

反相高效液相色谱法测定尿中吡啶醚和脱氧吡啶醚

尿中吡啶醚（ｐｙｒｉｄｉｎｏｌｉｎｅ,ＰＹＤ）和脱氧吡啶醚（ｄｅｏｘｙｐｙｒｉｄｉｎｏｌｉｎｅ,ＤＰＤ）是骨代谢特异的生化指标。应用高效液相色谱法（ＨＰＬＣ）建立了尿中ＰＹＤ和ＤＰＤ的测定方法。尿液用６ｍｏｌ／ＬＨＣｌ水解后,以纤维素ＣＦ１小柱提取,然后用ＨＰＬＣ测定;色谱系统为ＳｐｈｅｒｉｓｏｒｂＣ１８反相色谱柱,流动相组成为１５％甲醇添加０．１％七氟丁酸,流速为１．２ｍＬ／ｍｉｎ。系统的检测限：ＰＹＤ为１０ｎｍｏｌ／Ｌ,ＤＰＤ为７ｎｍｏｌ／Ｌ;回收率：ＰＹＤ为９１．５％,ＤＰＤ为１０６．１％;日内变异     

Sulfonate group-modified FePtCu nanoparticles as a selective probe for LDI-MS analysis of oligopeptides from a peptide mixture and human serum proteins

The availability of robust methods for the species-specific detection of meat and bone meal (MBM) in compound feedingstuffs is an important prerequisite to enforce current and upcoming European legislation on the use of processed animal proteins in animal nutrition. Among possible methods, those based on DNA turned out to be a reliable tool for this aim, since DNA is a quite thermostable molecule able to resist severe heat treatments applied in the manufacturing of animal meals. The application of such methods by control laboratories implies that the method has been validated including an assessment of its robustness. Successful transferability between laboratories is considered an important robustness criterion of the method. However, corresponding guidelines regarding the design of such a study relevant to this field are missing. Here, we demonstrate the feasibility of an alternative concept that was applied to check for the transferability of a qualitative assay for the detection of banned MBM in feedingstuffs at trace level based on real-time PCR. The concept was based on an experimental nested design applying analysis of variance (ANOVA) that was conducted independently in two laboratories and which allows for establishing major factors influencing the result of analysis. Statistical assessment of the results confirmed the importance of the DNA extraction/purification step utilised, whereas the PCR step turned out to be a minor factor regarding the overall variability of the results. Furthermore, blind samples comprised of compound feed adulterated with MBM at 0.1 % and blank compound feed were correctly classified as "positive" or "negative" samples, thus confirming fitness of purpose for the method. This approach can be of interest for other research groups working in the development of real-time PCR methods and in their use by control laboratories. Nested design of the study to check for the transferability of the real-time PCR method     

The use of poly(L-lactide-co-caprolactone) as a scaffold for adipose stem cells in bone tissue engineering: application in a spinal fusion model

Since the early 1990s, tissue engineering has been heralded as a strategy that may solve problems associated with bone grafting procedures. The original concept of growing bone in the laboratory, however, has proven illusive due to biological, logistic, and regulatory problems. Fat-derived stem cells and synthetic polymers open new, more practicable routes for bone tissue engineering. In this paper, we highlight the potential of poly(L-lactide-co-caprolactone) (PLCL) to serve as a radiolucent scaffold in bone tissue engineering. It appears that PLCL quickly and preferentially binds adipose stem cells (ASCs), which proliferate rapidly and eventually differentiate into the osteogenic phenotype. An in vivo spinal fusion study in a goat model provides a preclinical proof-of-concept for a one-step surgical procedure with ASCs in bone tissue engineering.