胰岛素受体介导主要信号传导途径与胰岛素抵抗的治疗进展

目的:了解胰岛素受体介导的主要的信号传导途径与胰岛素抵抗的关系,总结胰岛素抵抗的药物治疗方法。方法:主要选择被Medline收录的外文文献和在国内核心杂志上发表的有关文献,就其内容进行分析、分类、归纳及总结。结果:胰岛素受体、胰岛素受体底物、磷脂酰肌醇-3-激酶及葡萄糖转运蛋白4信号传递关键分子受损是导致胰岛素抵抗的主要原因。α糖苷酶抑制剂、双胍类、噻唑烷二酮类药物等纠正胰岛素信号传导通路中的障碍,增加靶组织对胰岛素敏感性的措施,都是胰岛素抵抗的治疗方法。结论:胰岛素信号转导途径的任何一个环节受损均可导致胰岛素抵抗。影响胰岛素受体介导的信号传导的新药开发将成为改善胰岛素抵抗的新趋向。     

自身免疫性肝炎大鼠模型外周血淋巴细胞体外培养与褪黑素的影响

目的:观察褪黑素对体外培养淋巴细胞增殖及促进细胞因子分泌的作用。方法:实验于2004-10/2006-10在解放军第一二三医院南京军区肝病中心实验室完成。①实验材料:Wistar大鼠,雄性,3月龄,体质量(230±20)g,购自上海斯莱克实验动物有限责任公司。褪黑素:美国Sigma公司产品。②实验方法:采用弗氏完全佐剂加肝细胞特异性脂蛋白法建立自身免疫性肝炎大鼠模型。分别抽取正常大鼠及模型大鼠的外周血,实验室常规培养,并将其分为3组:褪黑素组培养基中加褪黑素使终浓度为2mg/L;促肝细胞生长素组培养基中加促肝细胞生长素使终浓度为2mg/L;空白对照组培养基中不加任何细胞分裂刺激剂。③实验评估:培养48h后,对外周血淋巴细胞进行常规计数并采用液体闪烁计数仪记录1min计数结果值。用于观察褪黑素与促肝细胞生长素促进外周血淋巴细胞增殖的效果。并检测培养上清液中的各细胞因子浓度,用于观察褪黑素与促肝细胞生长素促进外周血淋巴细胞分泌细胞因子的作用。结果:①褪黑素对正常大鼠外周血淋巴细胞有促进增殖作用,细胞数与1min计数值较空白对照组明显升高(P<0.05),促肝细胞生长素无促进外周血淋巴细胞增殖作用。②褪黑素对模型大鼠外周血淋巴细胞有促进增殖作用,细胞数与1min计数值较空白对照组明显升高(P<0.05),促肝细胞生长素无促进外周血淋巴细胞增殖作用。③在褪黑素作用下,正常大鼠Th1细胞因子IL-2和IFN-γ水平明显高于空白对照组和促肝细胞生长素组(P<0.01),Th2细胞因子IL-6明显升高(P<0.05),IL-4水平与空白对照组比较,差异不显著(P>0.05),促肝细胞生长素组Th1和Th2细胞因子与空白对照组无明显差异(P>0.05)。④在褪黑素作用下,模型大鼠Th1细胞因子IL-2和IFN-γ水平较空白对照和促肝细胞生长素组明显升高(P<0.05),Th2细胞因子IL-4和IL-6水平与空白对照和促肝细胞生长素组无明显差异(P>0.05)。结论:褪黑素对自身免疫性肝炎大鼠外周血淋巴细胞有较强的刺激分裂作用。     

Dw/LD-related molecular polymorphism of DR4 β-chains

The results of this study demonstrate the existence of molecular heterogeneity (polymorphism) within DR β-chains isolated from a single serologically defined DR phenotype, DR4. The data are consistent with the possibility that this polymorphism is related to the Dw/LD phenotype as defined with the cellular reagents, homozygous typing cells.     

Acute and long-term effects of massive balloon dilation on the aortic wall and vasa vasorum

To investigate the acute and long-term effects on the vasa vasorum after massive overdilation, canine aortic segments were dilated with Gruentzig balloon catheters to more than 100% over normal size. In the acute study, the significant lumen increase was the result of intimal and medial rupture with stretching and thinning of the adventitia. In these areas, the vasa vasorum were stretched and severed, causing adventitial hemorrhage. In the chronic study, areas of previous subtotal wall rupture with adventitial thinning were repaired by scar tissue. This repair included formation of a neomedia, hyperplasia of the adventitia, and proliferation of the vasa vasorum. No progression of luminal dilatation was seen. This study showed that in subtotal aortic wall rupture, even a severely damaged adventitia is capable of preserving the lumen from further dilatation and rupture until healing. Blood flow to the damaged vessel wall was reestablished by revascularization via capillary budding in the aortic wall.     

颈外动脉栓塞用顺铂白蛋白微球的研究

用乳化化学交联法制备出适合于颌面部鳞癌殒外动脉栓塞用顺铂白蛋白微球;外观呈黄色粉末状,收率80±5%,显微观察呈圆球体,平场粒径56.3μm:药物含量为14.02～14.2%,包封率97.08～97.95%。对其体外释药、灭菌、稳定性及分散溶媒的处方进行了探讨。通过动物实验表明该微球可以达到理想的栓塞效果,并保证能在局部组织停留,有利于提高抗癌药物的疗效,降低毒副作用。     

人白血病HL60细胞的分化状态对细胞凋亡的影响

用细胞培养和流式细胞术等方法,研究人白血病HL60细胞诱导分化后,对三尖杉酯碱(Har)和喜树碱(Cam)诱导细胞凋亡的影响。结果表明,12-豆蔻酰及13-乙酸佛波酯以16nmol·L^-1浓度处理HL60细胞24h,细胞向单核/巨噬细胞方向分化,阻断于G_{1期;分化细胞抗Har和Cam诱导的细胞凋亡,但其c-myc基因的表达无变化。1.4%二甲基亚砜处理HL60细胞48h,细胞向粒细胞方向分化,阻断于G1期;分化细胞抗Cam,而不抗Har诱导的细胞凋亡;分化细胞的c-myc基因表达明显下降。结果提示,人白血病HL60细胞的分化状态,明显影响三尖杉酯碱和喜树碱诱导的细胞凋亡,但可能与c-myc基因的表达变化无关。}     

Vestibular loss as a contributor to Alzheimer’s disease

Alzheimer’s disease is a complex disorder whose etiology is still controversial. It is proposed that vestibular loss may contribute to the onset of Alzheimer’s disease, which initially involves degeneration of cholinergic systems in the posterior parietal-temporal, medial-temporal, and posterior-cingulate regions. A major projection to this system emanates from the semicircular canals of the vestibular labyrinth, with vestibular damage leading to severe degeneration of the medial-temporal region. The vestibular loss hypothesis is further supported by the vestibular symptoms found in Alzheimer’s patients as well as in various diseases that are major risk factors for Alzheimer’s disease.     

Near-UV/blue light-induced fluorescence in the human lens: potential interference with visual function

Irradiation of the ocular lens of numerous species by near-UV or short-visible wavelengths induces a blue-green fluorescence, which can be a source of intraocular veiling glare. Wavelengths longer than the approximately 365-nm lens absorption peak induce progressively weaker but also progressively more red-shifted fluorescence emission. The more red-shifted emission has a higher luminous efficiency and, in fact, earlier studies in this laboratory have demonstrated that the lens fluorescence in the nonhuman primate yields an approximately constant luminous efficiency when excited by equal radiant exposures over the wavelength range from 350 to 430 nm. Now, with the recent development and projected widespread use of "blue" diode lasers, a further study extending the measurements of the induced fluorescence efficiency and of the consequent veiling glare to the human lens seemed timely. The current study quantifies the fluorescence intensity induced in the human lens, both in terms of radiance and luminance, as a function of exciting light intensity, excitation wavelength, and subject age. The spatial distribution of the emitted fluorescence is also examined. These data are shown to imply that exposure to near-UV/blue wavelength sources at "safe" exposure levels (according to existing laser safety standards) can induce a veiling glare intense enough to degrade visual performance, and that the fluorescence intensity and consequent glare disruption show little dependence on subject age.