重组人血小板源性生长因子增加细胞外信号调节激酶磷酸化促进糖尿病大鼠全层皮肤缺损创面愈合

目的 在体观察重组人血小板源性生长因子（recombinant human platelet—derived growth factor，rhPDGF）促进糖尿病大鼠全层皮肤缺损创面修复可能涉及的细胞和分子机制，研究其可能涉及的信号通路。方法 26只糖尿病大鼠，每只动物背部制备4个全层皮肤缺损创面，选取其中52个创面，随机分成3组，即对照组，创面自然愈合；rhPDGF治疗组，创面rhPDGF用量为7．0μg／cm^2；赋形剂组，创面用等量赋形剂凝胶。观察治疗后3、7和14d创面肉芽形成、胶原沉积、再上皮化速率以及炎性细胞浸润情况，并采用免疫荧光和免疫组织化学技术观察创面周围和创面修复细胞内细胞外信号调节激酶1／2（extracellular signal—regulated kinase1／2，ERK1／2）磷酸化和增殖细胞核抗原（proliferative cell nuclear antigen，PCNA）的表达。结果 组织学观察，rhPDGF治疗组创面可见大量炎性细胞浸润，毛细血管胚芽及成纤维细胞明显多于另两组（P〈0．05）；胶原沉积明显，肉芽组织生长活跃，创面收缩显著，与对照组比较差异有统计学意义（P〈0．05）。免疫学研究显示，应用rhPDGF7～14d后，rhPDGF治疗组ERK1／2明显强于对照组和赋形剂组（P〈0．05）；且损伤后3～7d rhPDGF治疗组修复细胞PCNA的表达明显高于对照组和赋形剂组（P〈0．05）。结论 rhPDGF促糖尿病大鼠刨面愈合的作用部分是通过ERK1／2信号通路的磷酸化来完成的。     

Vascular endothelial growth factor in psoriasis: an indicator of disease severity and control

Background  Psoriasis is a chronic disease characterized by abnormal epidermal proliferation, inflammation and angiogenesis. It has been reported that vascular endothelial growth factor (VEGF) is overexpressed in lesional psoriatic skin and its serum levels are significantly elevated in patients with moderate to severe disease.
Objective  This study aims to evaluate the possible role of VEGF in the pathogenesis of psoriasis, and its significance as an indicator of disease severity and control.
Methods  Thirty patients with moderate to severe psoriasis and 10 healthy controls were subjected to baseline evaluation of VEGF. Patients were divided into three groups according to the received treatment: psoralen plus ultraviolet A (PUVA) thrice weekly (group 1), acitretin 50 mg daily (group 2), and combined PUVA twice weekly and acitretin 25 mg daily (group 3).Treatment continued for 16 weeks or up to clinical cure. Every patient was subjected to severity evaluation by Psoriasis Area and Severity Index (PASI) and measurement of serum VEGF before and after treatment.
Results  Mean serum levels of VEGF were significantly elevated in patients (327 ± 66.2 pg/mL) than control subjects (178 ± 83.4 pg/mL). A highly significant correlation was found between VEGF and PASI score, but not with other variables. The best clinical response, the least side-effects and the highest reduction of VEGF serum levels were achieved by the combined therapy.
Conclusion  The present study supported the proposed role of VEGF in the pathogenesis of psoriasis, and suggested that it could serve as a good indicator of disease severity and control.     

Angiolipoma of the buccal mucosa: a possible role of mast cell-derived VEGF in its enhanced vascularity

A case of angiolipoma occurring in the buccal mucosa of a 69-year-old male is described. The patient had noticed a painless mass in his buccal mucosa for 2 years. The surgically removed tumor, measuring 9 mm in diameter, was mainly located in the submucosal layer with focal expansion into the muscle layer. Histologically, the tumor was well-demarcated and composed of proliferations of mature fat cells and fibrous connective tissue containing many small blood vessels, which were evenly distributed. There was diffuse infiltration of a large number of mast cells, which were immunopositive for vascular endothelial growth factor (VEGF) especially around blood vessels, suggesting that VEGF produced by mast cells in angiolipomas plays an important role in the vascular proliferation in this particular tumor.     

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.