支气管哮喘患者痰嗜酸粒细胞相对计数与糖皮质激素治疗反应性的关系

目的观察支气管哮喘（简称哮喘）患者不同气道炎症类型（嗜酸粒细胞炎症与非嗜酸粒细胞炎症）对吸人糖皮质激素（简称激素）治疗的反应性。方法选择近3个月内未接受激素治疗的慢性持续性哮喘患者42例，根据诱导痰嗜酸粒细胞百分比将患者分为嗜酸粒细胞增高组（嗜酸粒细胞〉3％，23例）与非嗜酸粒细胞增高组（嗜酸粒细胞〈3％，19例），进行哮喘症状评分、肺功能检查、诱导痰细胞分类计数。采用酶联免疫荧光法测定痰液嗜酸粒细胞阳离子蛋白（ECP）的浓度。吸人激素治疗1、3个月时进行随访，重复上述哮喘疗效的评价指标。结果嗜酸粒细胞增高组痰嗜酸粒细胞比值、ECP水平基线值分别为0．080（0．063～0．178）、（324±149）μg／L，非嗜酸粒细胞增高组分别为0．017（0．006～0．021）、（152±68）μg／L，两组比较差异有统计学意义（t值分别为4．40、3．33，P均〈0、01）。嗜酸粒细胞增高组第一秒用力呼气容积（FEV1）、FEV1占预计值百分比（FEV1占预计值％）、症状评分的基线值分别为（1．98±0．67）L、（65±20）％、7．0（5．0～10．0）分，非嗜酸粒细胞增高组分别为（2．07±1．05）L、（66±27）％、5．0（2．0～9．0）分，两组比较差异无统计学意义（t值分别为-0．62、-0．09、1．32，P均〉0．05）。吸入激素治疗1、3个月后嗜酸粒细胞增高组的嗜酸粒细胞比值、ECP水平、症状评分、FEV1和FEV1占预计值％分别为[0．019（0．010～0．060）、[0．036（0．006～0．070）、（173±153）μg／L、（173±122）μg／L、3．0（1．0～6．0）分、3．0（1．0～5．0）分、（2．42±0．64）L、（2．43±0．76）L、（77±13）％、（77±18）％，与基线值比较差异有统计学意义（F值分别为6．73、6．71、5．93、7．38、5．78，P均〈0．05）。非嗜酸粒细胞增高组分别为0．013（0．000～0．025）、0．012（0．004～0．031）、（111±50）μg／L、（117±50）μg／L、3．0（0．0～6．0）分、3．0（1．0～7．3）分、（2．22±0．86）L、（2．21±0．24）L、（71±20）％、（65±21）％，与基线值比较，嗜酸粒细胞比值、FEV1和FEV1占预计值％均无统计学意义（F值分别为1．98、0．80、1．37，P均〉0．05），而ECP水平和症状评分比较差异有统计学意义（F值分别为3．78、3．59，P均〈0．05）。多元线性回归分析显示，病情严重度、基线FEV1和痰嗜酸粒细胞百分比与FEV1改善程度相关（r值分别为-0．27、-0．02、0．03，P均〈0．05）。痰嗜酸粒细胞比值的基线值对激素治疗反应的阴性预测值最高（89．5％）。结论对于痰嗜酸粒细胞增高的哮喘患者，吸人激素治疗能够抑制嗜酸粒细胞炎症，改善肺功能和症状评分。非嗜酸粒细胞增高哮喘患者对激素治疗反应性差，FEV1无改善。痰嗜酸粒细胞比值不高是激素治疗反应性差的最佳预测指标。     

早期激素治疗颅底骨折致迟发性面瘫的临床疗效

目的：观察颅底骨折致迟发性面瘫患者早期皮质激素治疗的疗效。方法回顾性分析颅底骨折致迟发性面瘫患者38例,早期（人院后立即给予）激素治疗20例,发现面瘫后给予激素治疗18例。治疗时间均1～2周,其他治疗相同。结果38例患者经保守治疗后均好转恢复,早期激素治疗的患者有效率95.0％（19/20）,恢复时间快;发现面瘫后给予激素治疗的有效率77.8％（14/18）,恢复时间慢。结论颅底骨折致迟发性面瘫患者早期激素治疗,可以明显提高迟发性面瘫患者的临床疗效。     

Differential effects of sympathetic nervous system and hypothalamic–pituitary–adrenal axis on systemic immune cells after severe experimental stroke

Infectious complications are the leading cause of death in the post-acute phase of stroke. Post-stroke immunodeficiency is believed to result from neurohormonal dysregulation of the sympathetic nervous system (SNS) and hypothalamic–pituitary–adrenal (HPA) axis. However, the differential effects of these neuroendocrine systems on the peripheral immune cells are only partially understood. Here, we determined the impact of the hormones of the SNS and HPA on distinct immune cell populations and characterized their interactions after stroke.At various time points after cortical or extensive hemispheric cerebral ischemia, plasma cortisone, corticosterone, metanephrine and adrenocorticotropic hormone (ACTH) levels were measured in mice. Leukocyte subpopulations were flow cytometrically analyzed in spleen and blood. To investigate their differential sensitivity to stress hormones, splenocytes were incubated in vitro with prednisolone, epinephrine and their respective receptor blockers. Glucocorticoid receptor (GCR) and beta2-adrenergic receptor (β2-AR) on leukocyte subpopulations were quantified by flow cytometry. In vivo effects of GCR and selective β2-AR blockade, respectively, were defined on serum hormone concentrations, lymphopenia and interferon-γ production after severe ischemia.We found elevated cortisone, corticosterone and metanephrine levels and associated lymphocytopenia only after extensive brain infarction. Prednisolone resulted in a 5 times higher cell death rate of splenocytes than epinephrine in vitro. Prednisolone and epinephrine-induced leukocyte cell death was prevented by GCR and β2-AR blockade, respectively. In vivo, only GCR blockade prevented post ischemic lymphopenia whereas β2-AR preserved interferon-γ secretion by lymphocytes. GCR blockade increased metanephrine levels in vivo and prednisolone, in turn, decreased β2-AR expression on lymphocytes.In conclusion, mediators of the SNS and the HPA axis differentially affect the systemic immune system after stroke. Moreover, our findings suggest a negative-feedback of corticosteroids on the sympathetic axis which may control the post-stroke stress-reaction. This complex interplay between the HPA and the SNS after stroke has to be considered when targeting the neurohormonal systems in the post acute phase of severe stroke.     

Adrenergic and glucocorticoid modulation of the sterile inflammatory response

Exposure to an intense, acute stressor, in the absence of a pathogen, alters immune function. Exposure to a single bout of inescapable tail shock increases plasma and tissue concentrations of cytokines, chemokines, and the danger associated molecular pattern (DAMP) Hsp72. Although previous studies have demonstrated that adrenergic receptor (ADR) and glucocorticoid receptor (GCR)-mediated pathways alter pathogen or microbial associated molecular pattern (MAMP)-evoked levels of cytokines, chemokines, and Hsp72, far fewer studies have tested the role of these receptors across multiple inflammatory proteins or tissues to elucidate the differences in magnitude of stress-evoked sterile inflammatory responses. The goals of the current study were to (1) compare the sterile inflammatory response in the circulation, liver, spleen, and subcutaneous (SQ) adipose tissue by measuring cytokine, chemokine, and DAMP (Hsp72) responses; and (2) to test the role of alpha-1 (α₁), beta-1 (β₁), beta-2 (β₂), and beta-3 (β₃) ADRs, as well as GCRs in signaling the sterile inflammatory response. The data presented indicate plasma and SQ adipose are significantly more stress responsive than the liver and spleen. Further, administration of ADR and GCR-specific antagonists revealed both similarities and differences in the signaling mechanisms of the sterile inflammatory response in the tissues studied. Finally, given the selective increase in the chemokine monocyte chemotactic protein-1 (MCP-1) in SQ tissue, it may be that SQ adipose is an important site of leukocyte migration, possibly in preparation for infection as a consequence of wounding. The current study helps further our understanding of the tissue-specific differences of the stress-induced sterile inflammatory response.     

HSP90和P23蛋白量和细胞亚定位在多发性骨髓瘤患者中的临床价值

目的：寻找预测MM患者GC敏感性指标。方法以MM患者作为研究对象,采用ELISA法检测MM患者血清HSP90浓度,Western Blot检测MM患者PBMNC中P23蛋白表达,探讨其与GC抵抗的关系。结果（1）MM患者血清HSP90含量明显比正常人高（P＜0.05）,且GC敏感组患者较GC抵抗组患者高（P＜0.05）,但各组P23血清浓度之间差异无统计学意义（P＞0.05）;（2）P23蛋白低表达患者和P23蛋白高表达患者治疗有效率分别为86%和33%,二者相比差异具有统计学意义（P＜0.05）,在5年随访中,前者生存率高于后者（P＜0.05）;（3）HSP90和P23蛋白在MM1.S、MM1.R细胞株以及GC敏感和抵抗的MM患者均位于胞浆内,无定位意义。结论血清HSP90和P23蛋白表达能预测MM患者对GC的敏感性和生存情况,可用此指标指导临床用药。     

凋亡相关蛋白在激素性幼兔股骨头缺血坏死动物模型中的表达及意义

目的 观察各凋亡相关蛋白在激素性幼兔股骨头缺血坏死动物模型股骨头组织中的表达情况,探讨该模型中调控凋亡的主要通路.方法 选用2月龄的新西兰大白兔,制作糖皮质激素性幼兔股骨头缺血坏死模型及对照组模型,根据是否发病将激素注射组分为未发病组和发病组.取股骨头软骨及软骨下骨组织用免疫组织化学法检测凋亡通路中凋亡相关蛋白天冬氨酸特异酶切的半胱氨酸蛋白酶-3(Caspase-3)、Caspase-8、人结合凋亡蛋白酶活化因子-1(apaf-1)、钙蛋白酶-1(calpain-1)的表达情况.分别测定在单位视野中Caspase-3、Caspase-8、apaf-1、calpain-1的积分光密度(IOD)值.结果 1.Caspase-3的IOD值分别为发病组25 142.72 ±21 528.48,未发病组2 069.63±1 096.96,对照组301.80±99.66.Caspase-8的IOD值分别为发病组24 942.63±18 942.99,未发病组2016.31±1 518.70,对照组236.85±97.94.Apaf-1的IOD值分别为发病组8 514.23±6 384.20,未发病组1 118.49±1 360.59,对照组95.13±38.05.Calpain-1的IOD值分别为发病组9 636.71 ±9 123.81,未发病组1 881.10±3 277.86,对照组126.71±47.35.Caspase-3在发病组和未发病组、对照组间差异有统计学意义(H=11.470、23.996,p＜0.01);Caspase-8在发病组和对照组间差异有统计学意义(H=22.178,P＜0.01);apaf-1在发病组和对照组间差异有统计学意义(H=22.808,P＜0.01);calpain-1在发病组和对照组间差异有统计学意义(H=13.553,P ＜0.01).2.线性回归分析:Caspase-8能够显著的预测Caspase-3,且回归方程回归效应显著,回归方程能够解释40.3％的变异,而apaf-1和calpain-1对Caspase-3的回归效应不显著.结论 凋亡受体通路可能在股骨头缺血坏死的凋亡过程中发挥主要调控作用.     

Effect of glucocorticoids on mechanisms of placental angiogenesis

The benefits of antenatal glucocorticoid (GC) treatment to promote human fetal lung maturation are well established. However, reports have emerged indicating that maternal exposure to high concentrations of circulating GCs alters placental and fetal development. Because many adult-onset metabolic and cardiovascular disorders have their origins in utero, the importance of prenatal conditions should be considered in detail. Therefore, this review aims to present an overview of the GC effect on placental and fetal development, specifically with regard to mechanisms of placental angiogenesis.We assumed that GC overexposure affects fetal development by altering placental angiogenesis. Disturbances in the development of the villous tree and pathological changes in the villous vascular system with insufficient uteroplacental blood flow have been linked to the pathogenesis of intrauterine growth retardation. Moreover, low birth weight is a serious risk factor known to correlate with an increased risk of adult-onset diseases. Although there have been many circumstances in which maternal GCs are elevated, we focused on exogenous synthetic GCs that are applied for therapeutic reasons. However, some questions about the use of steroids remain unanswered, which will require further studies that lead us to review alterations in placental angiogenesis under the perspective of GC overexposure.     

Glial Fibrillary Acidic Protein and Vimentin Expression Is Regulated by Glucocorticoids and Neurotrophic Factors in Primary Rat Astroglial Cultures

The neurotrophic factors epidermal growth factor (EGF), basic fibroblast growth factor, (bFGF), insulin‐like growth factor I (IGF‐I) and insulin (INS) regulate neural and astroglial cell functions. Glucocorticoids may influence the metabolism of astroglial compartment and are key hormones in neurodegenerative events. This study was designed to assess the interactions between growth factors and dexamethasone (DEX) on cytoskeletal proteins (GFAP and vimentin) expression in 25 days in vitro (DIV) astrocyte cultures. An increase in GFAP and vimentin expression was observed after 12 h pretreatment with bFGF and subsequent treatment for 60 h with DEX. GFAP immunoreactivity was decreased after 24 h progression growth factors (EGF, IGF‐I and INS) addition, when compared to control 36 h DEX and bFGF‐pretreated cultures for the last 12 h. Vimentin immunoreactivity was decreased after 12 h bFGF pretreatment and subsequent 60 h DEX addition in astrocyte cultures compared to 12 h bFGF‐pretreated ones. Pretreatment for 36 h with DEX plus bFGF in the last 12 h and subsequent treatment for 24 h with DMEM (Dulbecco's modified Eagle medium; DMEM) + BSA (bovine serum albumine) (harvesting), or with progression growth factors (EGF, IGF‐I or INS) alone or two of them together, stimulated GFAP expression, compared to untreated controls. Immunochemical analysis of the mitogen‐activated protein kinase ERK2 suggests an involvement of this enzyme in the control of GFAP expression. The above findings support the view of an interactive and complex dialogue between growth factors and glucocorticoids during astroglial cell proliferation and maturation in culture. This may have implications in therapeutic approach of neurologic disorders associated with astrogliosis, including cerebrovascular disease.     

不同剂量糖皮质激素预防患者冠状动脉旁路移植术后并发症的效果:meta分析

目的 采用meta分析评价不同剂量糖皮质激素预防患者冠状动脉旁路移植术后并发症的效果.方法 检索PubMed、EMbase、Highwire、CENTREN及其下属各临床注册试验数据中心、中国生物医学文献数据库和中国期刊全文数据库,检索时间限定2000年至2010年.收集冠状动脉旁路移植术患者给予不同剂量糖皮质激素预防术后并发症的随机对照研究.采用Cochrane协作网系统评价文献质量,并分析有关资料,主要包括术后房颤的发生情况、术后因高血糖需胰岛素治疗的情况、术后感染发生情况、术后死亡情况(住院期间或出院30 d内)和机械通气时间.采用RevMan 5.1软件进行meta分析.结果 纳入21项研究,共1737例患者.冠状动脉旁路移植术患者给予不同剂量糖皮质激素可降低术后房颤发生的风险,不增加各种原因感染及死亡的风险；中、大剂量增加因高血糖需要胰岛素治疗的风险；大剂量糖皮质激素患者机械通气时间延长.结论 冠状动脉旁路移植术患者给予不同剂量糖皮质激素可降低术后房颤的发生风险,且不增加感染和死亡的风险；中、大剂量可增加因高血糖需胰岛素治疗的风险；大剂量可增加机械通气时间延长的风险.     

Genotype–phenotype associations in understanding the role of corticosteroid-binding globulin in health and disease animal models

Corticosteroid-binding globulin (CBG) is a plasma glycoprotein discovered more than 60 years ago for its high-affinity for glucocorticoids. Although its molecular structure and its biochemical properties have been described, its various biological roles and its importance are not yet fully understood. This review focuses first on studies that have used no-hypothesis-driven genetic approaches in animal models to reveal the higher than expected importance of CBG in particular in glucocorticoid stress responses. Then the dissection of some CBG physiological roles in an animal model of genetic CBG deficiency is reported. Finally, studies on the role of CBG genetic variability in human obesity traits are reviewed and discussed.