Impaired hepatocyte survival and liver regeneration in Atm-deficient mice

Atm is a stress-induced DNA damage checkpoint protein kinase with multiple roles in cell-cycle progression. Recent evidence indicates that Atm also plays a role in stem cell maintenance and self-renewal. It is not known whether Atm has a role during tissue regeneration. Using liver regeneration as a model system, we examined the role of Atm in this process. Here, we show that the expression levels of Atm protein were gradually increased during liver regeneration and this was correlated with the onset of DNA replication. The induction of Stat3 and JNK signaling, which are essential processes in normal regeneration response, was attenuated during the early phases of liver regeneration in Atm-deficient mice. P53 was transiently phosphorylated at serine 23 during liver regeneration in an Atm-dependent manner. In addition, we found that cyclin A induction was delayed and p21 was over-expressed, both of these processes were correlated with reduced and delayed DNA replication in Atm(-/-) mice during liver regeneration. Finally, we show that increased apoptosis was observed in Atm(-/-) mice in response to partial hepatectomy, indicating that Atm is required for the survival of hepatocytes. Collectively, these data indicate that liver regeneration is impaired in Atm-deficient mice. Given that liver is the first line of defense against environmental toxins, the elucidation of the function of Atm and Atm-mediated signaling pathways in liver metabolism and in response to environmental toxins is of fundamental interest.     

海藻酸钙/聚组氨酸微胶囊的毒性试验研究

为了考察海藻酸钙/聚组氨酸微胶囊的毒性特征,我们利用MTT比色法和小鼠尾静脉注射法,分别考察了该微胶囊的细胞毒性和急性全身毒性。结果表明：微胶囊浓度≤1.0mg/mL时,材料对L929细胞生长无明显抑制作用;微胶囊浸提液即使在高浸提比（10.0mg/mL）下,浸提产物也无细胞毒性作用。急性全身毒性试验结果显示：微胶囊浸提液不引起急性全身毒性反应,表明微胶囊浸提液无有毒的沥滤物和降解产物产生。说明海藻酸钙/聚组氨酸微胶囊无明显毒性。     

增殖性瘢痕色度测量方法的研究

目的:临床评价增殖性瘢痕的颜色需要定量测量.本实验主要研究增殖性瘢痕色度的测量方法,实现瘢痕颜色的定量测量,为临床诊治提供量化依据.材料与方法:采用以光电积分式测量原理设计的色彩分析仪对增殖性瘢痕患者19人,共65个测试点按不同部位分为四组进行色度测量,并与正常组对照.用CIE-XYZ色度标准表达测量值,配合色度图直接观察瘢痕的疗效.结果:增殖性瘢痕各部位组的色度坐标值与相应的对照组比较均有显著性差异(P＜0.05).结论:本实验的测量方法是有效的,能准确、定量反映增殖性瘢痕颜色的变化.可用量化指标总结、分析、报告治疗结果.     

Induktion von endogenem Pyrogen und Interferon durch Newcastle Disease-Virus in vivo

Zusammenfassung Die Ausbildung von endogenem Pyrogen und Interferon wurde nach der Injektion von NDV im Kaninchen untersucht. Das Auftreten und das Verschwinden beider Substanzen stimmte nicht nur zeitlich, sondern auch quantitativ überein. Zudem verliefen die Bildungskurven von endogenem Pyrogen und Interferon sowohl im Blut als auch in den Organen weitgehend gleichsinnig. Eine Abweichung von diesem Verhalten wurde lediglich in der Milz beobachtet, indem hier das endogene Pyrogen bereits nach 1 Stunde, das Interferon jedoch erst nach 3 Stunden den höchsten Gipfel erreichte. Dieser Befund deutet daraufhin, daß das endogene Pyrogen und das Interferon zwei verschiedene Substanzen sind.Die Exstirpation der Milz hatte ein gleichzeitiges Absinken des endogenen Pyrogens und des Interferons im Blut, jedoch nicht in der Leber, der Lunge und der Niere zur Folge. Hinsichtlich der Entstehung der partiellen bzw. kompletten Toleranz gegenüber dem NDV bzw. Influenza Virus A (PR8) dürften die beiden Substanzen demselben Mechanismus unterliegen.

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Induction of endogenous pyrogen and interferon by newcastle disease virus in vivo

Summary Endogenous pyrogen and interferon induced by injection of rabbits with NDV were investigated. The appearance and disappearance of both substances were in parallel in time as well as in quantity. The curves of endogenous pyrogen and interferon in the blood and in various organs tested usually were also parallel. Only in spleen highest titers of endogenous pyrogen were found already 1 hour after inoculation, whereas interferon activity reached its peak only after 3 hours. This finding indicated that endogenous pyrogen and interferon may be different substances.In splenectomized animals the blood levels of endogenous pyrogen and interferon were lower than those found in intact animals, while the titers in liver, lung and kidneys were identical. In respect to the formation of partial or complete tolerance to NDV and influenza virus A (PR8), respectively, both substances appear to be subjected to the same mechanism.

     

阿糖胞苷纳米粒的制备及其释药规律研究

采用乳化聚合法制备阿糖胞苷纳米粒，研究其体内外释药特性。结果表明阿糖胞苷纳米粒体外释药规律符合双指数方程，有明显的缓释作用。在家兔体内的药物动力学过程符合二室模型，与阿糖胞苷注射剂相比，t1／2β和MRT延长，CL降低，表明阿糖胞苷纳米粒可显著延长阿糖胞苷在体内存留时间，具有明显的缓释特征。     

冷冻切片常遇到的问题及解决对策

目的 提高制作冷冻切片质量，确保实验结果科学性。方法 通过对切片机工作室温度设置选择，防卷板的调整应用及切片常遇到的问题分析，阐述提高制作高质量冷冻切片的方法。结果 通过对冷冻切片机有关参数的设定，提高了切片质量。结论 冷冻切片常遇到的问题，通过及时调整切片机相应设置，可以便捷解决。     

Peripheral nerve regeneration by microbraided poly(L-lactide-co-glycolide) biodegradable polymer fibers

Tiny tubes with fiber architecture were developed by a novel method of fabrication upon introducing some modification to the microbraiding technique, to function as nerve guide conduit and the feasibility of in vivo nerve regeneration was investigated through several of these conduits. Poly(L-lactide-co-glycolide) (10:90) polymer fibers being biocompatible and biodegradable were used for the fabrication of the conduits. The microbraided nerve guide conduits (MNGCs) were characterized using scanning electron microscopy to study the surface morphology and fiber arrangement. Degradation tests were performed and the micrographs of the conduit showed that the degradation of the conduit is by fiber breakage indicating bulk hydrolysis of the polymer. Biological performances of the conduits were examined in the rat sciatic nerve model with a 12-mm gap. After implantation of the MNGC to the right sciatic nerve of the rat, there was no inflammatory response. One week after implantation, a thin tissue capsule was formed on the outer surface of the conduit, indicating good biological response of the conduit. Fibrin matrix cable formation was seen inside the MNGC after 1 week implantation. One month after implantation, 9 of 10 rats showed successful nerve regeneration. None of the implanted tubes showed tube breakage. The MNGCs were flexible, permeable, and showed no swelling apart from its other advantages. Thus, these new poly(L-lactide-co-glycolide) microbraided conduits can be effective aids for nerve regeneration and repair and may lead to clinical applications.     

A Strain Device Imposing Dynamic and Uniform Equi-Biaxial Strain to Cultured Cells

The objective of this study is to design a new apparatus to allow the control of the magnitude and frequency of dynamic stretch applied uniformly to cells cultured on a silicon elastic membrane. The apparatus is designed to produce equi-biaxial dynamic stretches with area changes ranging from 0% to 55% and frequencies ranging from 0 to 2 Hz. Homogeneous finite strain analysis using triangles of markers was performed to compute the symmetric two-dimensional Lagrangian strain tensor on the membrane. Measurements of strain in both static and dynamic conditions showed that the shear component of the strain tensor (E_rc) was near zero, and that there was no significant difference between radial (E_rr) and circumferential (E_cc) components, indicating the attainment of equi-biaxial strain. Bovine aortic endothelial cells were transiently transfected with a chimeric construct in which the luciferase reporter is driven by TPA-responsive elements (TRE). The transfected cells cultured on the membrane were stretched. The luciferase activity increased significantly only when the cells were stretched by 15% or more in area. Cells in different locations of the membrane showed similar induction of luciferase activities, confirming that strain is uniform and equi-biaxial across the membrane. © 1998 Biomedical Engineering Society. PAC98: 8780+s, 8745-k, 8722-q     

不同给药途径的腺苷预处理对大鼠缺血再灌注心肌的保护

Objective To evaluate the effect on myocardial protection of adenosine preconditioning in different route of administration through right jugular vein and left ventricle.Methods 48 SD rats were randomly divided into ischemia reperfusion group(blank control),ischemic preconditioning group(IP,positive control),adenosine venous infusion group,adenosine in ventricular group,normal saline(NS)venous infusion group(negative control I)and NS in ventricular group(negative control Ⅱ).The ischemia reperfusion rats model were established in vivo,and then changes of heart function,serum cardiac troponin T (cTnT),superoxide dismutase(SOD),malondialdehyde(MDA)and expression of nuclear factor KB(NF-kB) were observed.Results SOD in IP[(208.63±23.88)U/ml],adenosine venous infusion group [(178.27±11.56) U/ml]and adenosine in ventricular group[(191.31±28.14)U/ml]were significantly higher than that in the ischemia reperfusion group[(145.05±23.18)U/ml](P<0.05),cTnT,MDA and expression of NF-kB were lower than that in the ischemia reperfusion group (P<0.05).Heart function was significantly better than that in the ischemia reperfusion group(P<0.05);SOD in adenosine in ventricular group was significantly higher than that in adenosine venous infusion group(P<0.05).cTnT,MDA and expression of NF-kB were lower than that in adenosine venous infusion group (P<0.05).Conclusion Adenosine preconditioning may mimic protective effect of ischemic preconditioning. The effect on myocardial protection of adenosine in ventricular group was better than that of adenosine venous infusion group.