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。     

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.

     

Altering dietary lysine:arginine ratio has little effect on cardiovascular risk factors and vascular reactivity in moderately hypercholesterolemic adults

BackgroundInformation is scarce regarding the effect of dietary protein type, with specific focus on the lysine-to-arginine (Lys:Arg) ratio, on cardiovascular risk factors and vascular reactivity in humans.ObjectiveDetermine the effect of dietary Lys:Arg ratio on cardiovascular risk factors and vascular reactivity in moderately hypercholesterolemic adults.DesignRandomized cross-over design of two 35-day diet phases; thirty adults (21 females and 9 males, ≥50 years, LDL cholesterol ≥120 mg/dL). Diets had 20% energy (E) protein, 30% E fat, 50% E carbohydrate and were designed to have low (0.7) or high (1.4) Lys:Arg ratio. Measures included fasting and postprandial lipid, lipoprotein, apolipoprotein concentrations; fasting high sensitivity C-reactive protein (hsCRP), small dense LDL (sdLDL) cholesterol, remnant lipoprotein cholesterol (RemLC), glycated albumin, adiponectin and immunoreactive insulin concentrations, endogenous cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) activities; cholesterol fractional synthesis rate (FSR); and flow mediated dilation (FMD) and peripheral artery tonometry (PAT).ResultsNo differences were observed in fasting and/or postprandial total, LDL, HDL and sdLDL cholesterol, RemLC, Lp(a) or apo B concentrations, LCAT and CETP activities, FSR, glycated albumin, immunoreactive insulin, FMD or PAT. The low, relative to the high, Lys:Arg ratio diet resulted in lower postprandial VLDL cholesterol (?24%, P = 0.001) and triglycerides (?23%, P = 0.001), and small but significant differences in fasting (?3%, P = 0.003) and postprandial (?3%, P = 0.018) apo AI, and fasting adiponectin concentrations (+7%, P = 0.035). Fasting and postprandial hsCRP concentrations were 23% lower after the low Lys:Arg ratio diet (P = 0.020 for both).ConclusionsDiets differing in Lys:Arg ratios had no or small effects on cardiovascular risk factors and vascular reactivity.     

人参皂甙Rg1对老年大鼠免疫功能的调节作用

已知老年机体免疫功能的降低与淋巴细胞增殖能力的减弱和白细胞介素-2(IL-2)产生减少有密切关系。以老年大鼠免疫功能为主要研究对象,首次发现人参皂甙Rg1无论体内给药还是体外实验均能选择性增强老年大鼠脾淋巴细胞增殖能力和IL-2的产生与释放,采用Northern和Western印迹分析法证明,Rg₁可明显促进IL-2基因和蛋白的表达,表现在IL-2mRNA和IL-2蛋白含量的显著增加。值得注意的是,在同样的条件下,Rg₁对青年大鼠免疫功能的影响并不显著,由此可以认为Rg1一种“免疫调节剂”,而并非单纯的“免疫增强剂”。     

Markers of oxidative stress and antioxidant activity in plasma and erythrocytes in neonatal respiratory distress syndrome

Markers of oxidative stress and antioxidant activity in plasma and erythrocytes were studied for 14 d after birth in infants with neonatal respiratory distress syndrome ( n = 9) and controls ( n = 36). In plasma, the total radical trapping antioxidant capacity and the chain-breaking antioxidants vitamin C, sulfhydryl groups and bilirubin were similar. The differences in uric acid levels were not consistent, but vitamin E levels and vitamin E/total-lipid ratio were lower in the neonatal respiratory distress group ( p < 0.01). In erythrocytes, the antioxidant enzymes glutathione peroxidase, glutathione reductase and superoxide dismutase did not differ postnatally. Indicators of oxidative damage in plasma (sulfhydryl/protein ratio and thiobarbituric acid reactive substances) showed the same postnatal course in both groups and were not influenced by oxygen therapy. In erythrocytes the reduced/oxidized glutathione ratio showed no consistent differences. In conclusion, this study, using erythrocytes and plasma, does not provide convincing evidence of oxidative damage and diminished antioxidant defenses in preterm infants with neonatal respiratory distress syndrome.     

催产素对妊娠末期大鼠蜕膜细胞内游离钙的刺激作用

妊娠末期催产素刺激子宫蜕膜细胞产生与分娩有关的前列腺素,但其作用方式仍未知。本实验分离妊娠19d大鼠蜕膜细胞,测定了催产素作用后蜕膜细胞内游离钙的变化,结果加入0.001～1μmol·L^-1催产素后,蜕膜细胞内[Ca²⁺]i出现瞬息增加,其峰值与催产素浓度呈剂量依赖关系,且此作用有自身钝化现象。说明催产素可能激活妊娠末期大鼠蜕膜细胞内的肌醇磷酯蛋白激酶C系统。给妊娠末期大鼠ip硫酸去氢表雄酮钠盐后分离的蜕膜细胞,催产素作用引起[Ca²⁺]i瞬息增加峰值较对照升高。