输尿管无细胞基质移植物的制备和评价

背景：与小肠黏膜下层等材料相比，脱细胞血管具有天然管状结构，与输尿管形态结构相近，替代输尿管时仅需端端吻合即可，手术操作简单，血管外壁光滑，获取及制备方法简便等优点。 目的：拟应用同种颈动脉血管无细胞基质体外构建输尿管。 设计、时间及地点：观察性实验，于2006-09/2008-06在上海交通大学医学院附属新华医院动物实验中心完成。 材料：长风杂交白猪由上海松联实验动物公司提供。上海交通大学医学院实验动物中心提供的健康成年大鼠8只，用于血管无细胞基质的动物毒性实验。 方法：剥去猪颈动脉血管外膜，PBS冲洗若干遍，然后将血管置于pH 7.1 的PBS中4 ℃下振荡清洗，0.5%十二烷基硫酸钠振荡24 h，后使用双蒸水4 ℃下反复振荡洗涤1周，每日换双蒸水2次。对于解剖过程中肌肉残留相对稍多的血管，在双蒸水洗涤前以混合消化液37 ℃下振荡消化约2 h，再行双蒸水洗涤。制备的无细胞基质置于青、链霉素溶液中，4 ℃保存，完成脱细胞支架制备。 主要观察指标：光镜及电镜观察脱细胞后管壁无细胞基质片的主要成分。将同种异体来源内皮祖细胞培养增殖后植入血管无细胞基质，观察细胞生长情况，并进行血管无细胞基质动物毒性实验。拉力实验了解血管无细胞基质材料的收缩性能。 结果：颈动脉血管无细胞基质中已无细胞成分，无细胞基质主要由胶原成分组成。扫描电镜未见该材料表面存在细胞及细胞碎片，同时发现该无细胞基质存在孔隙样结构。体外同种异体来源的内皮祖细胞培养增殖后植入血管无细胞基质，细胞黏附于无细胞基质。血管无细胞基质按毒性分级属于无毒级。拉力实验说明该无细胞基质具有一定的韧性和牵张性。 结论：采用胰酶和十二烷基硫酸钠制备的颈动脉血管无细胞基质材料无细胞残留，具有一定的韧性和牵张性，种植于其中的种子细胞具备一定的生长能力。     

Inhibition of the ubiquitin-proteasome system: a new avenue for atherosclerosis.

BACKGROUND: The ubiquitin-proteasome system (UPS) is thought to be functionally active in atherosclerosis (AS) lesions. Aspirin was found to be a potent inhibitor of the UPS in some tumour studies; however, its effect on AS remains to be demonstrated in vivo. METHODS: New Zealand rabbits were placed on a normal diet (N) or on a normal diet with aspirin (NI) or on an atherogenic diet without (H) or with aspirin (HI) for 12 weeks. Proteasome activity, concentrations of plasma lipids and levels of peroxidation were determined. Ubiquitin/ubiquitin-conjugates (Ub), IkappaBalpha, phosphorylated IkappaB (pIkappaBalpha) and p65 were investigated by Western blotting or immunochemistry. RESULTS: Concentrations of plasma lipids and peroxidation levels were higher in H or HI vs. N or NI. Histological analysis showed that atheroma was increased in H. Ub and IkappaBalpha were mainly localised in subendothelium and media vascular smooth muscle cells. Western blots revealed that Ub, IkappaBalpha, and pIkappaBalpha were increased, whereas p65 was lower in HI vs. H. The activity of the 20S proteasome was functionally active in H vs. N, NI or HI, while the 26S proteasome was not affected in any of the groups. CONCLUSIONS: Aspirin can attenuate the pathogenesis of atheroma formation, the degradation of IkappaBalpha and pIkappaBalpha, and lower the expression of p65, indicating that its therapeutic effects on AS may be via inhibition of the UPS.     

多发性肌炎的动物模型及雷公藤多甙对其疗效的研究

目的　寻找一种多发性肌炎的良好动物模型及其有效的治疗药物。　　方法　给动物注射同种大鼠的肌匀浆 ,观察其活动状态 ;通过肌肉组织染色及ELISA法 ,研究肌肉的病理学变化 ,同时给动物喂服雷公藤多甙观察药物疗效。　　结果　部分动物表现肌无力和肌萎缩 ,大多数肌肉组织学检查示肌纤维炎性变 ;免疫组化检查可见肌膜、肌内膜和肌束膜中有IgG沉积。动物服雷公藤多甙后肌肉病变明显减轻 ,其疗效与强的松相似。　　结论　用同种大鼠肌匀浆免疫动物可诱导出多发性肌炎的动物模型 ;雷公藤多甙能有效地治疗多发性肌炎。     

An etiological study on fulminant viral hepatitis]

Viral markers were studied in 79 cases of viral hepatitis with hepatic failure. The results were shown as follows: 8 cases were positive for anti-HAV IgM (10.12%); 76 cases positive for HBsAg or anti-HBc IgM (96.20%) and 41 cases positive for anti-HCV antibodies (51.89%). Among those with anti-HCV positive, 35 cases were co-infected with HBV, 5 cases with HAV and/or HCV, only one was infected with HCV alone 2 cases were HD-Ag positive (2.52%) and one not identified (1.27%). With the reference of clinical findings, patients co-infected with HBV/HCV or anti-HBc IgM positive were more critical and usually entail higher mortality. In cases with HCV co-infections, the positive HBV replication markers seems to be reduced. Hepatic failure without HBV replicative markers had a high rate of hepatic coma as well as poor outcome.     

Why study transport of peptides and proteins at the neurovascular interface

The blood–brain barrier (BBB) is an immense neurovascular interface. In neurodegenerative, ischemic, and traumatic disorders of the central nervous system (CNS), the BBB may hinder the delivery of many therapeutic peptides and proteins to the brain and spinal cord. Fortunately, the mistaken dogma that peptides and proteins do not cross the BBB has been corrected during the past two decades by the accumulating evidence that peptides and proteins in the periphery exert potent effects in the CNS. Not only can peptides and proteins serve as carriers for selective therapeutic agents, but they themselves may directly cross the BBB after delivery into the bloodstream. Their passage may be mediated by simple diffusion or specific transport, both of which can be affected by interactions in the blood compartment (outside the BBB) and within the endothelial cells (at the BBB level). Although the majority of current delivery strategies focuses on modification of the molecule to be delivered, understanding the mechanisms of transport will eventually facilitate regulation of the BBB directly. We review the different aspects of interactions and discuss recent advances in the cell biology of peptide/protein transport across the BBB. Better understanding of the nature and regulation of the transport systems at the BBB will provide a new direction to enhance the interactions of peripheral peptides and proteins with the CNS.