中药癌痛克对人肝癌细胞HepG2增殖、凋亡及Rb基因表达的影响

目的:通过观察不同浓度癌痛克对肝癌细胞株HepG2增殖及凋亡的作用,以及在相应状态下细胞内Rb基因表达量的改变,探讨中药癌痛克抗肝癌的可能作用机制。方法:实验于2005-09/2006-03在广州医学院中心实验室完成。取对数生长期的HepG2细胞,使细胞静止于G0/G1期。随机分为癌痛克2,10,50mg/L组和对照组,癌痛克2,10,50mg/L组分别加入对应浓度癌痛克(购自河南省肿瘤研究所,由金蝎、土元、九香虫、大黄、人参、灵芝、黄芪等纯中药组成的粉状制剂,功能:消癌肿、消癌痛、消积水、升白排毒),对照组不加药物,每组设4个复孔。MTT法检测各组细胞24,48,72h增殖率,细胞增殖率=[(A570癌痛克组-A570对照组)/A570对照组]×100%;以流式细胞术检测各组细胞24,48,72h凋亡率;RT-PCR方法检测各组细胞24,48,72h细胞内Rb基因mRNA表达量。结果:①2～50mg/L癌痛克具有明显的增殖抑制作用,癌痛克2,10,50mg/L组在24,48,72h与对照组比较,差异有显著性意义(P<0.05);3组各时点两两之间比较差异有显著性意义(P<0.05);同组各时点之间比较差异有显著性意义(P<0.05)。②2～50mg/L癌痛克组可诱导HepG2细胞凋亡,相同作用时间癌痛克2,10,50mg/L组与对照组比较差异有显著性意义(P<0.001);同一时点各组比较差异有显著性意义(P<0.05);同组不同作用时间点比较差异有显著性意义(P<0.001)。③2～50mg/L癌痛克可上调Rb基因的表达,各浓度组在各时点与对照组比较,差异均有显著性意义(P<0.05);24,48,72h癌痛克2,10,50mg/L组之间比较差异无显著性意义(P>0.05);3组各时点比较差异有显著性意义(P<0.05)。结论:中药癌痛克可通过抑制HepG2细胞增殖或诱导其凋亡,而发挥抗肝癌作用;且其诱导细胞凋亡的机制之一可能为通过增加Rb基因的表达而实现。     

Geographical variation in the incidence of acute myocardial infarction in eastern Finland--a Bayesian perspective

BACKGROUND: Large geographical variation in the incidence and mortality of cardiovascular disease (CHD) has been repeatedly reported in Finland with persistent difference between east and west. We undertook this study to estimate the geographical distribution of Acute Myocardial Infarction (AMI) incidence in the high-risk province of North Karelia and in the province of Kuopio. METHODS: Data on men aged 25-64 years with first event of acute myocardial infarction (AMI) were obtained from the FINMONICA AMI register, which recorded detailed information of AMI events during the period 1983 to 1992. The geographical pattern of AMI incidence was studied in two five-year periods 1983 to 1987 and 1988 to 1992 separately in 10 km x 10 km grid cells employing the Geographical Information System (GIS) and a Bayesian hierarchical approach. RESULTS: In both periods Bayesian modeling revealed a geographical pattern of AMI incidence and high risk (probability that incidence exceeds the observed mean incidence) in the remote rural areas. CONCLUSIONS: Detection of high-risk areas in both provinces showed that underlying environmental and/or genetic risk factors of AMI are not evenly distributed within the province but enriched in certain geographical non-administratively defined locations in eastern Finland.     

中频交变磁场照射后小鼠的行为学变化

目的:目前电磁辐射对生物体行为学方面的研究还很薄弱,设立不同磁场的强度和不同照射的周期,观察中频领域磁场照射对小鼠的自主活动和学习记忆的影响。方法:实验于2007-05-10/06-15在清华大学医学院和中国医学科学院药用植物研究所完成。①实验材料:磁场发生装置:中频交变磁场发生装置由清华大学工程物理系医学物理与工程研究所自主研发,可产生频率为40kHz,场强为28.8A/m,28.8kA/m的中频交变磁场。自主活动测试箱:中国医学科学院药用植物研究所提供,为一可封闭的金属箱,内置摄像头。4只黑色塑料测试桶分别置于箱子四角。水迷宫测试箱:中国医学科学院药用植物研究所提供。②实验动物及方法:将80只小鼠随机分为不同场强照射组和对照组。强磁场照射1组:11.6kA/m/40kHz,1h/d,连续照射7d。强磁场照射2组:11.6kA/m/40kHz,2h/d,连续照射7d。强磁场照射3组:11.6kA/m/40kHz,2h/d连续照射15d。弱磁场照射组:28.8kA/m/40kHz,2h/d,连续照射7d。对照组除了未放入磁场照射,其他条件与照射组一致。实验过程中对动物处置符合动物伦理学要求。③实验评估:观察其一般活动的改变,并采用自主活动测试箱和水迷宫测试箱进行测试,观察各组小鼠的自主活动和学习记忆的改变。结果:①一般行为观察:与对照组小鼠对比,经过中频交变磁场照射过的各组小鼠活跃度减低,毛色较差。强磁场照射3组(145G,2h/d,连续15d)于第11天和13天分别死亡1只。②自主活动检测结果:强磁场照射2,3组小鼠的运动路程、运动速度、运动时间明显低于对照组(P<0.05)。③水迷宫测试结果:在学习记忆检测阶段撤掉平台,发现各组动物2min内穿越平台原来所在象限的次数没有明显差别(P>0.05)。结论:中频交变磁场照射会给小鼠的自发活动造成一定影响,对学习记忆没有影响。     

口服糖皮质激素大鼠皮肤组织形态学变化

目的:观察口服糖皮质激素大鼠皮肤形态学改变,为建立新的皮肤衰老动物模型提供形态学上的依据。方法:实验于2006-07/2007-02在广东医学院药理教研室组织药理实验室完成。①实验对象:20只SD雄性SPF级大鼠随机分为两组,糖皮质激素组和空白对照组,每组10只。②实验方法:糖皮质激素组每天口服灌胃糖皮质激素3.5mg/(kg·d),空白对照组每天口服灌胃同等剂量生理盐水,喂养100d后麻醉下处死大鼠,取背部正中1cm×1cm大小皮肤组织检测相关指标。③实验评估:常规苏木精-伊红染色、VanGieson染色法、Weigert-间苯二酚-碱性品红染色法观察皮肤组织形态改变,并用计算机图像分析系统定量分析表皮厚度和弹力纤维总面积。结果:纳入结果分析16只,其中空白对照组8只,糖皮质激素组8只。糖皮质激素组大鼠皮肤表皮变薄,弹力纤维面积减少,胶原纤维多断裂,排列疏松,糖皮质激素组大鼠表皮厚度(33.8±3.1)μm,弹力纤维总面积(3557.9±373.1)μm2,均小于对照组大鼠表皮厚度(63.7±7.4)μm,弹力纤维总面积(5049.0±497.5)μm2。结论:糖皮质激素3.5mg/(kg·d)口服灌胃100d可导致大鼠皮肤衰老样改变,与人类皮肤衰老有相似形态学表现。     

Neuropeptide Y and Y2-receptor are involved in development of diabetic retinopathy and retinal neovascularization

BACKGROUND: Neuropeptide Y is a sympathetic neurotransmitter, a potent endothelium-derived angiogenic factor and a vascular mitogen. We have studied the role of the functional leucine7 to proline7 polymorphism of the signal peptide region of preproneuropeptide Y (prepro-NPY) as a genetic susceptibility factor for diabetic retinopathy. In addition, we investigated the role of the NPY Y2-receptor as a putative mediator of angiogenic NPY signaling in the retina. METHODS: Frequencies of proline7 (Pro7) carriers in the prepro-NPY were determined in type 1 and type 2 diabetes patients having retinopathy, in type 2 diabetes patients without retinopathy and in healthy control subjects. The role of Y2-receptor in hyperoxemia-induced retinal neovascularization was investigated in Y2-receptor knockout mice (Y2-/-) and in rats administered Y2-receptor mRNA antisense oligonucleotide. RESULTS: The carriers having Pro7 in the preproNPY are markedly over-represented among type 2 diabetes patients with retinopathy compared to type 2 diabetes patients without retinopathy and to the population control. Neonatal exposure to hyperoxia resulted in development of retinal neovascularization that was prevented in Y2(-1-) -mice, and significantly inhibited in rats treated with the Y2-receptor antisense oligonucleotide. CONCLUSIONS: NPY and Y2-receptor play important roles in diabetic retinopathy and retinal neovascularization and are thus potential new targets for drug molecules for treatment of retinopathy.     

Opportunistic infections and organ‐specific diseases in HIV‐1‐infected children: a cohort study (1990–2006)

Objectives

Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV infection in children, but there are few studies in the literature about the incidence of clinical manifestations after HAART in this population, compared with adults. The aim of this study was to describe the influence of the widespread use of HAART on the development of opportunistic infections and organ‐specific diseases in HIV‐infected children.

Methods

An observational study of a cohort of 366 vertically HIV‐infected children followed from 1990 to 2006 was carried out. According to the main antiretroviral protocol used, three calendar periods (CPs) were defined and compared: CP1 (1990–1996: no patients on HAART), CP2 (1997–1999: <60% on HAART) and CP3 (2000–2006: >60% on HAART).

Results

Children experienced a progressive increase in CD4 T cell count (P<0.05) and a decrease in HIV viral load from 1996 onwards (P<0.05). Similarly, rates of death, AIDS, opportunistic infections (bacteraemia, candidosis, cryptosporidiosis and bacterial pneumonia) and organ‐specific diseases (wasting syndrome, thrombocytopenia, cardiomyopathy, lymphoid interstitial pneumonia and HIV‐associated encephalopathy) were lower in CP2 and CP3 than in CP1.

Conclusions

This study provides evidence of improved clinical outcomes in HIV‐infected children over time and shows that mortality, AIDS, opportunistic infections and organ‐specific diseases declined as HAART was progressively instituted in this population.