Stimulation of Alpha-Adrenoceptors Facilitates the Release of Growth Hormone-Releasing Hormone from Rat Hypothalamus in vitro

While extensive evidence suggests that adrenoceptors play an important role in the control of growth hormone in the rat, there are few studies involving the direct measurement of growth hormone-releasing hormone (GHRH). We have therefore developed a radioimmunoassay for rat GHRH, and used it to investigate the modulation of GHRH release by noradrenaline from incubated rat hypothalamus in vitro. The GHRH radioimmunoassay had no significant cross-reactivity with other hypothalamic or GHRH-related peptides, and was sensitive to 4 pg/tube; intra- and interassay coefficients of variation were 6% and 12% respectively. Single incubated rat hypothalami produced a stable and readily measurable output of GHRH in successive 20 min incubations after an initial 60 min preincubation; the release of GHRH was increased in the presence of 56 mM KCI, but did not respond to KCI-depolarization when calcium was excluded from the medium. Stimulated GHRH release was identical to synthetic rat GHRH(1–43) on high-performance liquid chromatography and Sephadex G-75 chromatography.
Noradrenaline stimulated GHRH secretion in a dose-dependent manner in the concentration range 10⁻¹⁰— 10⁻⁶M, with a plateau in response at 10⁻⁷M. Stimulation with noradrenaline 10⁻⁷M was blocked by idazoxan 10⁻⁵M and attenuated by thymoxamine 10⁻⁵M, but was unaffected by timolol 10⁻⁵M. Both the α₂-adrenoceptor agonist guanfacine, and the α₁-adrenoceptor agonist methoxamine, specifically stimulated GHRH secretion.
It is concluded that noradrenaline stimulates the release of GHRH at both α₁ and α₂-adrenoceptors.     

老年与青壮年脑挫裂伤组织NGF的表达差异及意义

目的 研究衰老对脑挫裂伤组织神经生长因子（NGF）基因表达的影响,进一步探讨老年颅脑损伤病人神经功能缺失程度较重的分子生物学机制.方法 收集重型颅脑损伤开颅手术中的脑挫裂伤组织,应用免疫组化和医学数码图像分析技术,观察老年组（≥60岁）和青壮年组（19～59岁）病人脑损伤后3～9 h脑挫裂伤组织NGF蛋白的表达差异.结果 脑损伤后NGF在老年和青壮年脑挫裂伤组织中的表达均明显增强;老年组脑挫裂伤组织中的NGF蛋白表达显著性低于青壮年组（P＜0.05）.结论 老年人脑挫裂伤后NGF表达水平下降明显,提示其受损神经元的修复和生存能力降低,这可能是老年颅脑损伤病人恢复不良的重要原因之一.     

表皮生长因子对大鼠脑梗死后神经功能恢复的影响

目的 观察表皮生长因子（EGF）对大鼠脑梗死后神经功能恢复的影响。方法 采用肾血管性高血压大鼠制作一侧大脑中动脉皮层支闭塞（MCAO）模型。MCAO术后24 h，32只大鼠侧脑室注入10μl EGF（100μg/L），连续2d，共2μg（EGF组）；32只大鼠只注入不含EGF的等量溶液（对照组）。MCAO术后1、2、3和4w，行Bederson神经功能评分后，免疫印迹检测双侧大脑半球生长相关蛋白（GAP43）、突触囊泡蛋白（SYN）和胶质原纤维酸性蛋白（GFAP）的表达。结果 与同期对照组相比，EGF组大鼠在MCAO术后1、2w神经运动功能恢复更好，脑梗死灶同侧半球GAP43、SYN和GFAP有更早期和更高表达（P<0.05）。结论 GAP43、SYN和GFAP等蛋白的早期高峰表达可能与EGF引起的早期神经可塑性改善有关。     

雌激素提高皮瓣存活面积的实验性研究

目的研究不同剂量雌激素对皮瓣存活面积的影响,并探讨其作用机制。方法新西兰白兔30只,随机分为A、B、O三组。在兔背作超长型皮瓣,其蒂部注射雌激素,三组间剂量不同。术后检测皮瓣血管内皮生长因子（VEGF）、一氧化氮（NO）、皮瓣存活面积（S）等指标。结果A组、B组皮瓣的NO、VEGF、S较O组增加;皮瓣存活面积S与VEGF表达、NO含量之间呈正相关。结论雌激素处理可使皮瓣VEGF表达上调、NO含量增加。     

Bone growth patterns in Chinese children and adolescents: a 6-year follow-up study provides evidence for sexual dimorphism and tracking

Summary We prospectively examined bone growth patterns in 894 children aged 6–17 years at the baseline visit, with a 6-year follow-up. Results show bone “tracking” over a six-year interval and sexual dimorphism of bone attained levels and timing of peak bone growth. Our findings underscore childhood and adolescence as critical periods for building bone and developing gender differences. Introduction Bone growth patterns were prospectively examined in 894 Chinese children (496 males), aged 6–17 yrs, from a population-based twin cohort. Whole-body bone area (BA), bone mineral content (BMC), and bone mineral density (BMD) were measured by DEXA at baseline and a 6-yr follow-up. Methods Graphic smoothing plots and generalized estimating equations were used to model bone attained levels, growth, and “tracking”. Results Attained levels of BMC and BA increased curvilinearly with age. Male attained levels were higher than females after age ∼15 yr, but BMD was lower between 13–17 yrs (Tanner stage I to IV). In both genders, peak BMC and BMD growth lagged ∼2 yrs behind peak BA growth, which lagged 2 yrs behind peak height growth. Peak bone growth occurred 1–3 yrs later in males. Over the 6-yr follow-up, all bone measurements “tracked”, but “shifting” across ranks also occurred, and baseline tertile ranking influenced bone growth. Females with early menarche had higher attained levels than females with late menarche at age 12–13 yrs. Conclusion Our findings confirm and expand previous studies on peak bone growth conducted in Caucasian cohorts, particularly sexually dimorphic and maturational effects. The significant “tracking” of bone measurements in this 6-yr follow-up study underscores the importance that osteoporosis prevention should begin in childhood and adolescence. Fengxiu Ouyang and Binyan Wang contributed equally to this article. Source(s) of support: This study is supported in part by grant R01 HD049059, R01 HL0864619 and R01 AR045651 from the National Institute of Health and by the Food Allergy Project.     

Stage line diagram: An age‐conditional reference diagram for tracking development

This paper presents a method for calculating stage line diagrams, a novel type of reference diagram useful for tracking developmental processes over time. Potential fields of applications include: dentistry (tooth eruption), oncology (tumor grading, cancer staging), virology (HIV infection and disease staging), psychology (stages of cognitive development), human development (pubertal stages) and chronic diseases (stages of dementia). Transition probabilities between successive stages are modeled as smoothly varying functions of age. Age‐conditional references are calculated from the modeled probabilities by the mid‐P value. It is possible to eliminate the influence of age by calculating standard deviation scores (SDS). The method is applied to the empirical data to produce reference charts on secondary sexual maturation. The mean of the empirical SDS in the reference population is close to zero, whereas the variance depends on age. The stage line diagram provides quick insight into both status (in SDS) and tempo (in SDS/year) of development of an individual child. Other measures (e.g. height SDS, body mass index SDS) from the same child can be added to the chart. Diagrams for sexual maturation are available as a web application at http://vps.stefvanbuuren.nl/puberty . The stage line diagram expresses status and tempo of discrete changes on a continuous scale. Wider application of these measures scores opens up new analytic possibilities. Copyright © 2009 John Wiley & Sons, Ltd.     

Mathematical modelling of the spatio-temporal response of cytotoxic T-lymphocytes to a solid tumour.

In this paper a mathematical model describing the growth of a solid tumour in the presence of an immune system response is presented. In particular, attention is focused upon the attack of tumour cells by so-called tumour-infiltrating cytotoxic lymphocytes (TICLs), in a small, multicellular tumour, without necrosis and at some stage prior to (tumour-induced) angiogenesis. At this stage the immune cells and the tumour cells are considered to be in a state of dynamic equilibrium--cancer dormancy--a phenomenon which has been observed in primary tumours, micrometastases and residual disease after ablation of the primary tumour. Nonetheless, the precise biochemical and cellular mechanisms by which TICLs control cancer dormancy are still poorly understood from a biological and immunological point of view. Therefore we focus on the analysis of the spatio-temporal dynamics of tumour cells, immune cells and chemokines in an immunogenic tumour. The lymphocytes are assumed to migrate into the growing solid tumour and interact with the tumour cells in such a way that lymphocyte-tumour cell complexes are formed. These complexes result in either the death of the tumour cells (the normal situation) or the inactivation (sometimes even the death) of the lymphocytes. The migration of the TICLs is determined by a combination of random motility and chemotaxis in response to the presence of chemokines. The resulting system of four nonlinear partial differential equations (TICLs, tumour cells, complexes and chemokines) is analysed and numerical simulations are presented. We consider two different tumour geometries--multi-layered cell growth and multi-cellular spheroid growth. The numerical simulations demonstrate the existence of cell distributions that are quasi-stationary in time and heterogeneous in space. A linear stability analysis of the underlying (spatially homogeneous) ordinary differential equation (ODE) kinetics coupled with a numerical investigation of the ODE system reveals the existence of a stable limit cycle. This is verified further when a subsequent bifurcation analysis is undertaken using a numerical continuation package. These results then explain the complex heterogeneous spatio-temporal dynamics observed in the partial differential equation (PDE) system. Our approach may lead to a deeper understanding of the phenomenon of cancer dormancy and may be helpful in the future development of more effective anti-cancer vaccines.     

血管内皮生长因子在高原脑水肿形成中作用的实验研究

目的:探讨血管内皮生长因子(VEGF)在高原脑水肿形成中的作用。方法:建立大鼠模拟高原模型,应用脑干湿重比率法定量脑水肿情况、应用荧光素钠透过率测定BBB通透性、应用实时荧光定量RT-PCR法检测脑组织VEGF mRNA含量以及应用蛋白印迹法半定量脑组织VEGF含量。结果:大鼠在高原24 h后脑组织含水率明显增高(P<0.05),荧光素钠透过率显著增加(P<0.01);VEGF mRNA转录及其表达显著增高(P<0.001)。结论:VEGF表达在高原脑水肿形成中起重要作用。     

三氧化二砷对CO2气腹下小鼠肿瘤腹壁戳口种植影响的实验研究

目的 研究腹腔内注射三氧化二砷(arsenic trioxide,As2O3)对小鼠CO2气腹下肝癌H22转移的影响. 方法 昆明鼠40只(清洁级),中腹部穿刺置入1 mm套管针,自套管针注入1×106肿瘤细胞后,建立CO2气腹,压力8 mm Hg,时间30 min.术后随机分4组,每组10只,分别腹腔内注入生理盐水,1 ml;As2O3(2 mg/kg),1 ml;As2O3(4 mg/kg),1 ml;As2O3(4mg/kg)+肝素(10 U/ml),共1 ml.气腹后第3、7天测量肿瘤黏附因子(CD44)、血管内皮生长因子(vascular endothelial growth factor,VEGF)的变化;比较各组生存状态、腹围、体重变化及转移瘤直径.结果 气腹后第3、7天,与对照组相比,各As2O3组CD44、VEGF表达均明显降低(P＜0.05).2个高剂量组的气腹后第3天VEGF、第7天CD44比低剂量组降低明显(P＜0.05).4组戳口种植率分别为9/10、8/10、7/10、6/10,差异无显著性(x2=2.667,P=0.446). 结论 As2O3对CO2气腹腹腔镜肿瘤生长转移有抑制作用.     

运用siRNA建立稳定低表达IGF1R基因的肝癌细胞株的实验研究

目的运用siRNA技术在肝癌细胞株中建立稳定低表达人胰岛素样生长因子1类受体(IGF1R)基因的细胞株。方法构建包含封闭IGF1R基因的真核表达载体pSUPER-IGF1R-siRNA,转染SMMC7721和Hep3B细胞,G418筛选表达稳定的细胞株。通过RT-PCR、Western-blot分析与鉴定IGF1R mRNA和蛋白及cyclin D1、cyclinB1蛋白的表达,并绘制细胞生长曲线。结果在SMMC7721和Hep3B细胞中成功建立低表达IGF1R基因的细胞株,其生长明显减慢(P<0.05),且其cyclinD1表达亦明显下降(P<0.05)。结论pSUPER-IGF1R-siRNA能抑制SMMC7721和Hep3B细胞的生长。