Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.     

联合应用SSH和cDNA表达谱芯片筛选肝星状细胞早期活化的相关基因

目的利用抑制消减杂交(suppressionsubtractivehybridization,SSH)和cDNA表达谱芯片筛选早期活化的肝星状细胞(hepaticstellatecell,HSC)和大鼠正常肝脏组织、轻度肝纤维化组织、重度肝纤维化组织中差异表达的基因。方法从SSH构建的大鼠轻度肝纤维化、重度肝纤维化2个差异cDNA文库中挑选1000条上调显著的基因,与正常大鼠4136条基因克隆制作成一张芯片,筛选早期活化的肝星状细胞相关基因。结果获得与HSC早期活化相关的上调基因有202条,下调基因有80条,其中血清和糖皮质激素调节蛋白激酶(serumandglucocorticoidsensitivekinase,SGK)在正常大鼠基因克隆和2周及8周SSH上调差异基因中均呈上调信号。结论联合应用SSH和cDNA表达谱芯片是筛选和鉴定不同样本中差异表达基因的快速、经济和有效的方法;SGK可能作为多种细胞信号传导通路和细胞磷酸化级联反应的一个功能性交汇点,参与了肝星状细胞的早期活化和信号传导。     

应用抑制消减杂交和cDNA表达谱芯片筛选肝星形细胞持续活化的相关基因

目的：利用抑制消减杂交（suppression subtractive hybridization,SSH）和cDNA表达谱芯片筛选早期活化的肝星状细胞与大鼠正常肝脏组织、轻度肝纤维化组织、重度肝纤维化组织中差异表达的基因.方法：从SSH构建的大鼠轻度和重度肝纤维化中两个差异cDNA文库中挑选1 000条上调显著的基因,与正常大鼠4 136条基因克隆制作成一张芯片,筛选持续期活化的肝星状细胞相关基因.结果：获得与HSC持续活化相关的上调基因633条,下调基因715条,其中血清和糖皮质激素调节蛋白激酶（SGK）在正常大鼠基因克隆和2、8周SSH上调差异基因中均呈上调信号.结论：联合应用SSH和cDNA表达谱芯片是筛选和鉴定不同样本中差异表达基因的快速、经济和有效方法;SGK可能作为多种细胞信号传导通路和细胞磷酸化级联反应的一个功能性交汇点,参与了肝星状细胞的早期活化和信号传导.     

Hormone receptors in vestibular schwannomas

Summary The possibility that steroid hormones play a role in vestibular schwannoma proliferation has been suggested by a number of investigators. There is conflicting information about the presence of steroid hormone receptors in these tumors. The aim of this study was to examine the expression of androgen, progesterone, glucocorticoid and estrogen receptor messenger ribonucleic acid levels (mRNA) in twenty-one vestibular schwannomas by either Northern blot analysis or the polymerase chain reaction (PCR).Glucocorticoid receptor mRNA was expressed in all twentyone tumors examined. Only two male specimens were positive for androgen receptor mRNA expression by PCR-Southern blot analysis. Thirty-three percent of the schwannomas (7/21) showed a strong band for progesterone receptor mRNA by PCR-Southern blot analysis; there were an equal number of males and females in this group. Estrogen receptor mRNA levels were undetectable in all tumors examined by PCR-Southern blot analysis. These studies suggest that the pattern of steroid receptor expression is different in schwannomas than in meningiomas. Individual vestibular schwannomas need to be examined for their steroid receptor mRNA expression mRNA expression to know whether they will be responsive.     

Glucocorticoid regulation of eicosanoid production by glial cells under basal and stimulated conditions

We measured the production of two eicosanoids, prostaglandin E₂ and thromboxane-B₂, by rat glial cell cultures under basal conditions, following stimulation with phorbol-12-myristate-13-acetate and the bacterial endotoxin lipopolysaccharide, and following treatment with synthetic glucocorticoids. Stimulation of rat glial cells in culture with either phorbol-12-myristate-13-acetate or lipopolysaccharide caused a 1.5–5.0-fold increase in prostaglandin E₂ production, but did not affect thromboxane production. Pretreatment of the cultures with dexamethasone markedly inhibited the stimulated production of prostaglandin E₂ but had only a modest effect on basal production. Dexamethasone did not affect the activity of the enzyme protein kinase C, a putative regulator of eicosanoid synthesis. Our findings show that glucocorticoids have the potential to modulate central nervous system eicosanoid production particularly under conditions of stimulated production, such as inflammatory and demyelinating disorders. This mechanism may explain, at least in part, the therapeutic benefit of glucocorticoids in patients with multiple sclerosis.     

Effects of Glucocorticoid on Electrical Activities of Hippocampal Neurons in vitro

Intracellular recording of the rat hippocampal slices was established and usedto analyse the effects of glucocorticoid on resting membrane potential as well as inputresistance of the cells in CA1 and CA2 of hippocampal slices.The results indicate thatwithin 1-2 min the steroid hyperpolarized some of the hippocampal neurons with atendency of increasing the cells' input resistance,suggesting that glucocorticoid caninfluence the function of central neurons in a non-genomic pattern,and the underlyingmechanism involves the change of resting membrane potential.     

糖皮质激素受体高、低亲和力位点在急性淋巴细胞性白血病治疗中的意义

研究了１０例正常人和２９例急性淋巴细胞性白血病（急淋）患者外周血糖皮质激素受体高、低亲和力结合位，或（ＧＣＲＨ、ＧＣＲＬ），利用Ｒｕ３８４８６对ＧＣＲＬ进行封闭，对部分患者ＧＣＲＨ、ＧＣＲＬ在激素联合化疗前后水平的变化进行了动态观察。结果表明，正常对照组ＧＣＲＨ、ＧＣＲＬ分别为４６０８±１８８９位点／细胞和１３５２３８±８８５０９位点／细胞，两者相关良好。急淋患者ＧＣＲＨ、ＧＣＲＬ分别为６０５２±３８８８位点／细胞和１２６４０５±１０２１３３位点／细胞，经过糖皮质激素药物联合化疗后，其水平分别为３６１６±１９６２位点／细胞和１４３５９７±１１２２８９位点／细胞，ＧＣＲＨ下降明显（Ｐ＜０．０１），下降率为４０．３％；而ＧＣＲＬ化疗前后差异不显著（Ｐ＞０．０５）。提示ＧＣＲＬ在介导糖皮质激素联合化疗疗效的维持中起重要的作用。     

The anti-inflammatory profile of fluticasone propionate

Fluticasone propionate is a new corticosteroid based on the androstane nucleus. It is more lipophilic than beclomethasone dipropionate (BDP) and budesonide, and binds more avidly to human lung tissue. It has an absolute affinity (K_D) of 0.5 nM for the glucocorticoid receptor and a relative receptor aflinity 1.5- and 3.0-times greater than that of beclomethasone-17-monopropionate (17-BMP) and budesonide, respectively. The rate of association with the receptor is faster and the rate of dissociation slower than with standard corticosteroids. As a result, the half-life of the corticosteroid-receptor complex is >10 h. Fluticasone propionate is also highly selective for the glucocorticoid receptor, with little or no activity at other steroid receptors. Pretreatment with fluticasone propionate signiflcantly inhibits the increase in mast cell numbers in the nasal mucosa of rats chronically exposed to toluene di-isocyanate (TDI), and suppresses TDI-induced mast cell degranulation. It is more potent in vitro than dexamethasone, BDP and budesonide in inhibiting anti-CD3-induced human T-lymphocyte proliferation, in attenuating tumour necrosis factor-α-induced endothelial cell adhesion molecule expression, and in increasing secretory leucocyte protease inhibitor levels in airway epithelial cells. It is also more potent and longer-acting than other corticosteroids in inhibiting oedema formation, interleukin-5 (IL-5)-induced blood eosinophilia, and IL-5- or platelet activating factor-stimulated eosinophil accumulation in the lung. Fluticasone propionate therefore has increased intrinsic glucocorticoid potency and high topical anti-inflammatory activity.     

Studies on the function and regulation of low－affinity glucocorticoid receptor

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