7周递增运动负荷训练过程中糖皮质激素受体的变化

目的为探讨不同运动负荷量作用后的机体靶细胞糖皮质激素受体(GR)变化特征。方法复制相应的动物运动模型,观察7周递增运动负荷训练过程中不同运动负荷量作用后大鼠肝胞液GR结合量的变化。采用竞争性蛋白结合分析法检测血浆皮质酮浓度;放射配体结合分析法测定靶细胞胞液糖皮质激素受体结合量。结果运动后GR减少呈运动负荷量依赖性。结论7周递增负荷运动过程中,GR呈渐进性减少,在运动至第7周时达最低点。     

糖皮质激素治疗ARDS疗效论文的回顾性分析评价

伴随着循证医学( evidence basedmedicine,EMB)的兴起,过去那种仅凭借临床经验、直觉或病理生理原理来处理患者的传统医疗模式受到了冲击〔1 ,2〕。现代医学模式要求在经验医学的基础上,强调根据科学研究的依据来制订疾病的预防和治疗方案。肾上腺糖皮质激素在临床上用于治疗急性呼吸窘迫综合征( acute respiratory distress syndrom e,ARDS)已有多年的历史,其主要的依据是:ARDS的病理基础是肺泡毛细血管膜通透性增高,应用糖皮质激素可以减少毛细血管内液体的渗出。但目前学术界对应用糖皮质激素治疗ARDS的临床效果存有争议。为了系统…     

失血大鼠肝、脑组织糖皮质激素受体的变化及其意义

探讨动物失血后肝、脑组织糖皮质激素受体（ＧＲ）的变化及其意义。成年雄性ＳＤ大鼠，麻醉后经颈动脉插管放血０～４０％，或肌注不同剂量的Ｒｕ４８６以阻断组织的ＧＲ０，５０％和８０％。结果：大鼠失血０～４０％后３小时，肝、脑组织胞液ＧＲ量随失血量增加而进行性下降；大鼠失血３０％后０～３小时，肝、脑组织ＧＲ含量随失血持续时间延长而进行性减少；组织ＧＲ与失血量、失血持续时间呈显著的负相关。预先阻断大鼠ＧＲ０、５０％和８０％后再放血１０％，结果ＧＲ阻断率越大，则大鼠颈动脉压越低，时间存活率越小。提示：失血可引起组织ＧＲ减少，失血量越大、失血持续时间越长，ＧＲ减少越明显；ＧＲ可作为反映动物失血严重程度及判断其预后的重要指标     

急性呼吸窘迫综合征患者糖皮质激素合理使用方案及受体机制

目的：研究急性呼吸窘迫综合征(ARDS)患者糖皮质激素受体(GR)及皮质醇的变化，提出ARDS患者糖皮质激素(GC)的合理使用方案及其受体机制。方法：研究综合性ICU内ARDS患者，采用放射配体结合测定法测定外周血白细胞GR特异结合位点，并结合临床监测指标将患者分为轻、中、重3型，提出的GC使用方案在临床反复得到验证。结果：根据ARDS患者的GR及内源性GC(皮质醇)水平使用GC是合理的。结论：个体化的GC使用方案有利于提高ARDS的救治成功率。     

糖皮质激素吸入疗法对小儿骨代谢和肾上腺功能的影响

目的 探讨糖皮质激素吸入疗法对哮喘患儿骨代谢、骨密度和肾上腺功能的影响。方法 60 例哮喘患儿随机分为治疗组和对照组各30例,另设普通肺炎对照组30例。治疗组给予普米克气雾剂吸入治疗(200~600μg/d),必要时高压雾化吸入β2激动剂或吸入β2 激动剂气雾剂,口服西替利嗪;对照组不吸入普米克,其他处理同治疗组。比较 3 组患儿的骨代谢、骨密度和肾上腺功能。结果 治疗18个月后,3组患儿的骨代谢、骨密度和肾上腺功检测指标无显著性差异( P >0.05)。结论 哮喘患儿接受糖皮质激素吸入治疗是安全的。     

Septic serum induces glucocorticoid resistance and modifies the expression of glucocorticoid isoforms receptors: a prospective cohort study and in vitro experimental assay

Background

A protective role for glucocorticoid therapy in animal models of sepsis was shown many decades ago. In human sepsis, there is new interest in glucocorticoid therapy at a physiological dose after reports of improved response to vasopressor drugs and decreased mortality in a selected group of patients. However, other reports have not confirmed these results. Cellular glucocorticoid resistance could explain a possible cause of that. To evaluate this hypothesis, we evaluated the expression of glucocorticoid receptor beta, the dominant negative isoform of glucocorticoid receptor, in peripheral mononuclear cells of septic patients and the effect of serum septic patients over glucocorticoid receptor expression and glucocorticoid sensitivity in immune cells culture.

Methods

A prospective cohort study and an in vitro experimental study with matched controls were developed. Nine patients with septic shock and nine healthy controls were prospectively enrolled. Mononuclear cells and serum samples were obtained from the patients with sepsis on admission to the Intensive Care Unit and on the day of discharge from hospital, and from healthy volunteers matched by age and sex with the patients. Glucocorticoid receptor alpha and beta expression from patients and from immune cell lines cultured in the presence of serum from septic patients were studied by western blot. Glucocorticoid sensitivity was studied in control mononuclear cells cultured in the presence of serum from normal or septic patients. A statistical analysis was performed using a Mann-Whitney test for non-parametric data and analysis of variance for multiple comparison; P < 0.05 was considered significant.

Results

The patients'' glucocorticoid receptor beta expression was significantly higher on admission than on discharge, whereas the alpha receptor was not significantly different. In vitro, septic serum induced increased expression of both receptors in T and B cells in culture, with a greater effect on receptor beta than the control serum. Septic serum induced glucocorticoid resistance in control mononuclear cells.

Conclusion

There is a transient increased expression of glucocorticoid receptor beta in mononuclear cells from septic patients. Serum from septic patients induces cell glucocorticoid resistance in vitro. Our findings support a possible cell glucocorticoid resistance in sepsis.     

Glucocorticoid sensitivity and inflammatory status of peripheral blood mononuclear cells in patients with coronary artery disease

Objective: Mechanisms behind sustained inflammation in patients with coronary artery disease (CAD) are not clarified but hypothalamus-pituitary-adrenal (HPA) axis dysfunction may have a role. Here, we investigated whether inflammatory status of peripheral blood mononuclear cells (PBMCs) was associated with altered glucocorticoid sensitivity in CAD patients.

Methods: In 55 CAD patients and 30 controls, mRNA levels of GR-α, GR-β, NF-κB, IκBα, MMP-9 and TIMP-1 were measured in PBMCs. Suppressive effects of dexamethasone on GR-α, GR-β, NF-κB, IκBα, MMP-9 and TIMP-1 mRNA levels were assessed in PBMCs ex vivo. Salivary cortisol was repeatedly measured over 3 days.

Results: GR-α mRNA levels were higher in CAD patients than in controls, 0.50 (0.38–0.59) versus 0.26 (0.18–0.37), p?p?p?p?Conclusions: PBMCs from CAD patients displayed an inflammatory gene expression profile. This was not explained by reduced glucocorticoid sensitivity. Instead, inflammation was associated with increased expression of GR-α mRNA, suggesting a hypocortisolemic state.

• Key messages

• ??Peripheral blood mononuclear cells from patients with coronary artery disease (CAD) display an inflammatory gene expression profile.

• ??This inflammatory state cannot be explained by reduced glucocorticoid sensitivity in CAD patients.

• ??Instead, the inflammatory gene expression profile is associated with upregulated levels of glucocorticoid receptor-α mRNA, suggesting a hypocortisolemic state.

     

嗜酸性粒细胞增多症伴皮肤损害1例

收治1例嗜酸性粒细胞增多症伴皮肤损害的男性患者,26岁,以周身皮肤脱屑、散在皮肤破溃为主要症状就诊,实验室检查提示嗜酸性粒细胞明显升高,结合骨髓穿刺、淋巴结活检结果,临床诊断为嗜酸性粒细胞增多症,给予醋酸泼尼松治疗后病情好转。     

糖皮质激素治疗早、中期肝衰竭临床疗效观察

目的 观察糖皮质激素治疗早、中期肝衰竭的疗效.方法 62例肝衰竭早、中期患者随机分为内科治疗组（对照组）和激素治疗组（治疗组）,对照组采用保肝、退黄、支持等治疗,治疗组在此基础上加用氧化可的松琥珀酸钠,观察患者临床症状,生化学指标及激素不良反应.结果 治疗组好转率明显高于对照组,激素治疗没有增加患者严重不良反应发生率.结论 小剂量糖皮质激素对早、中期肝衰竭患者具有良好效果,且不良反应较少,可明显提高存活率.     

来氟米特联合糖皮质激素治疗IgA肾病疗效观察

目的观察来氟米特联合糖皮质激素治疗IgA肾病的疗效和安全性。方法IgA肾病患者60例,随机分为治疗组和对照组各30例,治疗组给予醋酸泼尼松联合来氟米特片口服;对照组仅给予醋酸泼尼松片口服,用法、用量同治疗组;2组疗程均为12个月。分别于治疗前及治疗后1、3、6、12个月测定2组24h尿蛋白定量、血浆白蛋白、血清肌酐、收缩压、舒张压水平,并比较2组疗效和不良反应发生情况。结果治疗后12个月,治疗组总有效率（93.3％）高于对照组（70.0％）（P〈0.05）,2组完全缓解率、不良反应发生率比较差异无统计学意义（P〉0.05）;治疗前及治疗后各时间点,2组血清肌酐、收缩压及舒张压比较差异无统计学意义（P〉0.05）;治疗组治疗后3、6、12个月,对照组治疗后6、12个月24h尿蛋白定量与白蛋白水平与治疗前比较差异有统计学意义（P〈0.05）;治疗后12个月,治疗组24h尿蛋白定量水平低于对照组,白蛋白水平高于对照组（P〈0.05）。结论来氟米特联合糖皮质激素在减少IgA肾病尿蛋白,升高血浆白蛋白水平上优于单用糖皮质激素。     

吸入糖皮质激素引致口腔念珠菌病的护理

[目的]探讨吸入糖皮质激素引致口腔念珠菌病的护理对策。[方法]回顾性总结2009年1月2010年12月在我院呼吸科收住的吸入糖皮质激素后出现口腔念珠菌病的老年病人,并依据是否使用3％碳酸氢钠液漱口随机将病人分为两组：对照组47例雾化吸入糖皮质激素治疗后给予生理盐水漱口;观察组50例雾化吸入糖皮质激素治疗后给予3％碳酸氢钠液漱口。总结对比两组病人的口腔拭子培养阳性标本数、出现口腔白斑覆盖的时间并进行分析。[结果]观察组口腔拭子培养阳性标本比例18％明显低于对照组的78．7％,口腔白斑覆盖比例16％明显低于对照组的74．4％,差异均有统计学意义（P〈0．05）。观察组出现口腔拭子培养阳性标本的时间7．7d±2．33d,明显晚于对照组的5．7d±1．71d,口腔白斑覆盖的时间8．7d±2．11d,明显晚于对照组的5．8d±2．3d,差异有统计学意义（P〈0．01）。[结论]雾化吸入糖皮质激素治疗后加强口腔护理能预防、控制口腔念珠菌病。     

Effect of clarithromycin on endogenous glucocorticoid levels in mice

The efficacy of erythromycin (EM) and clarithromycin (CAM) is well documented for the management of chronic inflammatory respiratory tract disease. However, the precise mechanism of action of these drugs is still controversial. We previously reported that EM increased serum glucocorticoid (GC) levels and suggested that this increase may be a mechanism of action of the drug. To investigate whether other macrolides had similar activity, we studied the effect of a new macrolide, CAM, on serum GC levels in mice. Intraperitoneal injections of CAM increased the serum GC levels in a dose-dependent manner, with the increase completely suppressed by pretreatment with dexamethasone. These results suggest that CAM increases serum GC levels through activation of the hypothalamo-pituitary adrenocortical axis, and that the antiinflammatory activity of CAM appears to exert its influence via an increase in serum GC levels.     

乳腺癌组织中Kaiso和糖皮质激素受体的表达及临床意义

目的研究转录因子Kaiso和糖皮质激素受体(glucocorticoid receptor,GR)在乳腺癌组织中的表达及其与乳腺癌临床病理参数的关系。方法用免疫组织化学法研究81例不同临床分期女性乳腺癌组织及39例乳腺增生组织中Kaiso和GR的表达情况与亚细胞定位,并对其与乳腺癌临床病理参数进行相关性分析。结果Ⅲ期乳腺癌患者Kaiso阳性表达率95.3%(41/43)高于Ⅰ+Ⅱ期阳性表达率52.6%(20/38),且Ⅲ期乳腺癌患者GR阳性表达率95.3%(41/43)也高于Ⅰ+Ⅱ期阳性表达率55.3%(21/38),差异均具有统计学意义(P均0.01);有淋巴结转移患者的乳腺癌组织中Kaiso、GR阳性表达率(84.8%,88.9%)均高于无淋巴结转移的乳腺癌组织(61.1%,61.1%),差异有统计学意义(P均0.05)。而Kaiso、GR的表达与乳腺癌患者的性别、年龄以及癌组织分化程度均无明显相关性(P0.05)。Kaiso、GR的表达在Ⅰ期和Ⅱ期乳腺癌组织细胞中均呈现出胞质、胞核增强的现象,而在Ⅲ期乳腺癌主要表达于细胞核。81例乳腺癌组织中,Kaiso与GR阳性表达例数分别为61例和62例,二者阳性率呈高度正相关(r=0.967,P0.01)。结论胞质、胞核中Kaiso和GR同时表达增强与乳腺癌高临床分期和淋巴结转移有明显相关性,两者可能在乳腺癌的发生、发展中发挥重要作用。     

儿童急性播散性脑脊髓炎42例临床分析

目的总结儿童急性播散性脑脊髓炎的临床特征。方法回顾性分析42例急性播散性脑脊髓炎患儿的临床资料。结果 42例患儿中脑型39例,脊髓型3例;发病前有上呼吸道感染36例,疫苗接种史4例,无明显诱因者2例;临床表现为发热8例,抽搐17例,嗜睡5例,昏迷7例,性格改变15例,头痛、呕吐19例,语言障碍8例,肢体功能障碍7例,排便困难3例,脑神经受累7例;脑膜刺激征阳性14例,病理征阳性35例,肌张力增高8例;脑脊液检查异常32例,正常10例;42例均行头颅MRI检查,其中39例出现异常信号,3例无异常;16例行脊髓MRI检查,3例表现异常;应用糖皮质激素治疗后治愈37例,5例留有后遗症。结论感染和疫苗接种是儿童发生急性播散性脑脊髓炎主要诱因,MRI对其诊断有重要价值,早期应用糖皮质激素治疗可改善预后。     

GR、Hsp90表达与前列腺癌生物学行为的关系

【目的】探讨糖皮质激素受体 (GR)和热休克蛋白 90 (Hsp90 )与前列腺癌雄激素非依赖发生的关系。【方法】根据临床雄激素阻断治疗效果将前列腺癌 (PC)患者分为雄激素依赖 (ADPC)组和雄激素非依赖(AIPC)组 ,根据手术及病理进行临床分期、病理分级 ,应用免疫组化对手术标本进行GR、Hsp90检测 ,并分析其与临床生物学行为的关系。【结果】AIPC组织中GR、Hsp90表达明显升高 ( P <0 .0 1) ,GR表达与前列腺癌的分化程度密切相关 ,Hsp90表达与病理分级有密切关系。在AIPC组织中GR和Hsp90的表达之间存在明显的正相关 (r =0 .6 6 4 ,P <0 .0 5 )。【结论】GR抑制了前列腺癌细胞的分化 ,Hsp90的高表达促进了前列腺癌的进展 ,两者的表达及活性增高促进了前列腺癌的雄激素非依赖进展