氯屈膦酸二钠合成工艺改进

目的：对氯屈膦酸二钠的合成工艺进行了研究。方法：以二溴甲烷和亚膦酸三异丙酯为原料,经缩合,氯化,热裂解和成盐反应得到氯屈膦酸二钠。结果：合成产物的化学结构经元素分析,红外光谱,质谱和核磁共振谱确证,总收率为60．3％。结论：此合成路线是完全可行的。     

转小鼠TNFα基因大鼠脑缺血时TNFα表达对小胶质细胞激活的影响

目的：观察转小鼠TNFα基因大鼠脑缺血再灌流不同时间TNFα表达的动态变化及其对小胶质细胞激活的影响。方法：采用线栓法制作大鼠大脑中动脉闭塞模型,用TNFα、整合素QM(OX42)免疫组化染色观察转小鼠TNFα基因大鼠未缺血脑组织及缺血1h再灌注3h、12h、24h、72h、7d时的TNFα表达及小胶质细胞激活状态。结果：转小鼠TNFα基因大鼠缺血1h再灌注3hTNFα表达较未缺血脑组织明显增加,并达峰值,缺血1h再灌注12～72h,TNFα表达仍较显著,但随时间的延长逐渐减少,再灌注7d时,TNFα表达接近缺血前水平。转小鼠TNFα基因大鼠脑组织小胶质细胞缺血1h再灌注3h小胶质细胞极显著地被激活,并达峰值;缺血1h再灌注12h、24h、72h、7d时脑组织小胶质细胞与未缺血脑组织比较显著被激活,但随时间的延长,小胶质细胞激活状态逐渐接近缺血前的水平。结论：脑缺血再灌注后TNFα表达的动态变化与小胶质细胞激活的动态变化完全一致,提示脑缺血再灌注后小胶质细胞的激活主要与TNFα的过度表达有关。     

常染色体16三体胎鼠和正常同窝鼠肠神经系发育

目的 研究Ｄｏｗｎ综合征动物模型常染色体１６三体胎鼠及其正常同窝鼠肠神经系发育状况。方法 （１）将ＮＭＲ－１雌鼠与携带有两个Ｒｏｂｅｒｔｓｏｎｉａｎ（Ｒｂ）易位（１１,１６）,Ｒｂ（１６,１７）８Ｌｕｂｔ＾ＷＬｕｂ３雄鼠进行交配,繁殖常染色体１６三体胎鼠。（２）采用细胞遗传学分析,以检出两条Ｒｂ染色体和４１条染色体者定为常染色体１６三体胎鼠。（３）采用高度特异的神经标记物蛋白基因产物９．５抗体进行     

TRIPS,the Doha Declaration and increasing access to medicines: policy options for Ghana

There are acute disparities in pharmaceutical access between developing and industrialized countries. Developing countries make up approximately 80% of the world's population but only represent approximately 20% of global pharmaceutical consumption. Among the many barriers to drug access are the potential consequences of the Trade Related Aspects of Intellectual Property Rights (TRIPS) Agreement. Many developing countries have recently modified their patent laws to conform to the TRIPS standards, given the 2005 deadline for developing countries. Safeguards to protect public health have been incorporated into the TRIPS Agreement; however, in practice governments may be reluctant to exercise such rights given concern about the international trade and political ramifications. The Doha Declaration and the recent Decision on the Implementation of Paragraph 6 of the Doha Declaration on the TRIPS Agreement and Public Health may provide more freedom for developing countries in using these safeguards. This paper focuses on Ghana, a developing country that recently changed its patent laws to conform to TRIPS standards. We examine Ghana's patent law changes in the context of the Doha Declaration and assess their meaning for access to drugs of its population. We discuss new and existing barriers, as well as possible solutions, to provide policy-makers with lessons learned from the Ghanaian experience.     

Mutations in the C-terminal domain of Sonic Hedgehog cause holoprosencephaly

Holoprosencephaly (HPE) is the most common brain anomaly in humans, involving abnormal formation and septation of the developing central nervous system. Among the heterogeneous causes of HPE, mutations in the Sonic Hedgehog (SHH) gene have been shown to result in an autosomal dominant form of the disorder. Here we describe a total of five different mutations in the processing domain encoded by exon 3 of SHH in familial and sporadic HPE. This is the first instance in humans where SHH mutations in the domain responsible for autocatalytic cleavage and cholesterol modification of the N-terminal signaling domain of the protein have been observed.      

组织工程技术仿生构建颅颌骨组织的研究

目的:探索构建组织工程化仿生骨种植体的方法流程,并制备成骨细胞-可吸收载体种植体样品,同时尝试建立组织工程化非承载骨种植体的评价方法。方法:实验于2001-05/2005-12分别在天津市口腔医院组织工程实验室和天津大学材料学院高分子材料研究所完成。①通过相分离技术制备壳聚糖/明胶三维网络多孔支架,在支架材料表面原位沉积纳米级的羟基磷灰石晶体,构筑纳米羟基磷灰石/壳聚糖/明胶仿生骨组织工程支架材料,并进行表征和性能检测。②用酶消化法和条件培养法分离、诱导培养中国小型猪成骨细胞作为组织工程种子细胞。③用静态复合共培养法体外构建2种骨组织工程种植体样品:成骨细胞-纳米羟基磷灰石/壳聚糖/明胶仿生骨种植体,成骨细胞-纳米羟基磷灰石/胶原种植体。④采用扫描电镜、透射电镜、FDA荧光、LDH、MTT等定期观测仿生骨样品中细胞形态、细胞增殖速率、碱性磷酸酶活性、矿化结节形成等指标,以比较样品的细胞增殖活性和成骨活性。结果:①成功构筑了具有良好的生物相容性和力学相容性的纳米羟基磷灰石/壳聚糖/明胶,这种材料具有适于细胞黏附与生长的(90±1)%的孔隙率,孔径为100￣300μm的微孔结构,且原位沉积的纳米羟基磷灰石晶体的粒径为50nm左右,接近与天然骨的组成。②自中国小型猪腿骨成功分离培养了成骨细胞,并在诱导培养条件下,表现出很强的增殖活力和成骨活性,适合作为实验用骨组织工程的种子细胞。③成功构建了两种成骨细胞-可吸收载体种植体样品:经检验仿生构建的小型猪成骨细胞-纳米羟基磷灰石/壳聚糖/明胶种植体具有细胞亲和性和体外成骨活性。结论:①在体外成功仿生构建了结构与活性接近天然骨的骨组织工程种植体--纳米羟基磷灰石/壳聚糖/明胶种植体。②初步建立了仿生组织工程化非承载骨种植体的评价方法,为其进一步用于体内修复颅颌骨组织损伤的深化研究提供了实验数据和科学依据。     

Syngeneic bone marrow transplantation reduces the hearing loss associated with murine mucopolysaccharidosis type VII

MPS VII mice are deficient in beta-glucuronidase and share many clinical, biochemical, and pathologic characteristics with human mucopolysaccharidosis type VII (MPS VII). We have shown that syngeneic bone marrow transplantation (BMT) prolongs survival and reduces lysosomal storage in many organs of the MPS VII mouse. In this report, we quantify the hearing loss and determine the impact of syngeneic BMT on the development of deafness and the associated pathology in the MPS VII mouse. Eleven weeks after syngeneic BMT performed at birth, treated MPS VII mice had normal auditory-evoked brainstem responses (ABR), whereas untreated MPS VII mice had ABR thresholds 43 dB higher than normal. Treated MPS VII mice had beta-glucuronidase-positive cells in the temporal bone and in the subepithelial connective tissue of the external auditory canal. There was less thickening of the tympanic membrane and middle ear mucosa and decreased distortion of the ossicles and the cochlear bone. Although transplanted MPS VII mice had increased ABR thresholds by 33 weeks of age, four of the six had thresholds 12 to 32 dB lower than untreated mutants. These data indicate that syngeneic BMT in newborn MPS VII mice prevents early hearing loss and, in some animals, results in long-term improved auditory function.     

Immunohistochemical study on gastroenteric nervous system in trisomy 16 mice:an animal model of Down syndrome

AIM:To study the development of gastroenteric nervous system in trisomy 16 mouse embryos.The gastroenteric nervous system in trisomy 16 mice and their normal littermates, serving as controls from embryonic days 13 to 18 (ED13-18) was identified by using primary antibody against protein gene product (PGP) 9.5.METHODS:Trisomy 16 mouse breeding and trisomy 16 mouse embryos were identified from their normal littermates by chromosome examination; PGP 9.5 immunohistochemical stainning.RESULTS:In normal littermates embryos, the precursor cells from the neural crest migrated into stomach and intestine at ED 13 and ED 14 respectively.Numerous nervous processes connected to each other and formed early nervous networks at ED 14 stomach and ED 15 intestine. Original ganglia in the muscular nervous plexus of the stomach appeared at ED15 with very simple arrangement. At ED 16 the early developed myenteric nervous plexuses were regularly found in the stomach and intestine respectively. In both stomach and intestine, the development of submucosal nervous plexuses were finished at ED17. However, the myenteric nervous plexus and the internal and external submucosal nervous plexuses were differentiated only in the stomach at ED 18.In comparison with the normal littermates, stomach and intestine nervous system developed much slower in trisomy 16 mice. Their immature neurons did not appear in the stomach and intestine until ED 14 and ED 15. Between ED 14 and ED 16, the gastroenteric nervous system was composed of only some scattered neurons with different distribution density and size. The development and differentiation of the gastroenteric nervous system were delayed and the myenteric nervous plexus did not appear until ED 18. There was no submucosal nervous plexus in all stomach and intestine specimens. A semiquantitative analysis and rank sum test of the data showed that the trisomy 16 mouse embryos were markedly retarded in the gastroenteric nervous development compared with their normal littermates.CONCLUSION:Trisomy 16 mice, as an animal model for Down syndrome, has abnormality not only in several systems and organs but also in gastroenteric innervation. This report describes for the first time that the development of the gastroenteric nervous system was not only delayed but also pathological.