Development of an automated blood sampling system for use in humans

Many hormones are released in a pulsatile or burst-like pattern resulting in fluctuating blood levels that can undergo rapid modulation by physiological and pathological signals. To accurately measure these changes in hormone concentration requires frequent blood sampling, often over extended periods as the overall rhythmicity may vary over 24 hours. The aim of this study was to develop a computerized, automated blood sampling system which allows repeated stress-free blood sample collection from humans over an extended period under basal or test conditions. The system incorporates a peristaltic pump, fraction collector and standard infusion pump together with a custom built electronic control unit linked to a personal computer. Disposable tubing prevents cross-contamination between study participants. The computer programme is modifiable to adjust for the number of specimen tubes and volume of blood collected per sampling cycle. Patency of the collecting line is maintained with 0.9% saline, without the need for heparinization. To validate the system, 10-minute samples for cortisol were collected over 24 hours from five healthy volunteers, of whom two had additional concomitant ACTH sampling. Deconvolution analysis revealed an expected number of hormone secretory episodes and a non-pathological degree of orderliness within the data. There was high concordance between ACTH and cortisol secretory events. The ability of the system to allow multiple measurements and of the software program to link with other physiological monitoring equipment provides a powerful tool to study physiologic/pathophysiologic change in relation to blood hormone and other biomarker levels.     

Effect of repetitive transcranial magnetic stimulation on the cognitive impairment induced by sleep deprivation: a randomized trial

ObjectiveCurrently, an efficient method for improving cognitive impairment due to sleep deprivation (SD) is lacking. The aim of this study is to evaluate the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) during SD on reversing the adverse effects of SD.MethodsA total of 66 healthy people were randomized into the rTMS group and sham group. Both groups were deprived of sleep for 24 h. During SD, participants were asked to complete several cognitive tasks and underwent mood assessments. Saliva cortisol levels, plasma concentrations of brain-derived neurotrophic factor (BDNF), precursor BDNF (proBDNF), and tissue-type plasminogen activator (tPA), and frontal blood activation were detected before and after SD. The rTMS group received real rTMS stimulation for 2 sessions of 10 Hz rTMS (40 trains of 50 pulses with a 20-second intertrain interval) to the left dorsolateral prefrontal cortex and the sham group received sham stimulation during SD.ResultsTwenty-four hours of SD induced a reduced accuracy in the n-back task, increases in both anxiety and depression, increased cortisol levels, decreased frontal blood activation and decreased BDNF levels in healthy people. Notably, rTMS improved the hyperactivity of the hypothalamic-pituitary-adrenal axis and decreased frontal blood activation induced by SD, and reduced the consumption of plasma proBDNF.ConclusionsTwenty-four hours of SD induced a cognitive impairment. The administration of high-frequency rTMS during sleep deprivation exerted positive effects on HPA axis and frontal activation and might help alleviate cognitive impairment in the long term.     

The roles of cortisol and pro-inflammatory cytokines in assisting the diagnosis of autism spectrum disorder

Autism spectrum disorders (ASD) is a severe neurodevelopmental disorder characterized by impairments in social interaction and repetitive behaviors. Diagnosis of ASD is currently phenotype based with no reliable laboratory test available to assist clinicians. The desire for clinically useful and reliable biomarkers is strong. Researches have shown that individuals with autism often exhibit dysfunction of hypothalamic–pituitary–adrenal (HPA) axis and cytokines. The purpose of this study was to evaluate diurnal variation of cortisol (cortisol VAR), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) as potential biomarkers for ASD. The present results demonstrated that in comparison to the healthy controls, the individuals with autism showed a lower level of cortisol VAR, higher level of IL-6 and TNF-α. The levels of cortisol VAR, IL-6 and TNF-α have significantly correlations with the severity of ASD measured by CARS scores. The results of ROC analysis indicated the cortisol VAR, IL-6 and TNF-α were potential biomarkers in diagnosis of ASD. The combination of three factors performed the best sensitivity and specificity for diagnosis of ASD. Therefore, the present study may reveal a simple clinical approach with great potential for assisting the diagnosis of ASD.     

老年患者人工髋关节置换术后认知功能障碍与血浆皮质醇水平的关系

目的：探讨老年患者人工髋关节置换术后认知功能障碍（POCD）与血浆皮质醇水平的关系。方法80例老年骨折患者在腰硬联合麻醉下接受人工髋关节置换术,于术前1 d 及术后6 h、1 d、3 d、7 d 检测其外周血血浆皮质醇水平,并采用简易精神状态检查量表（MMSE）评价其认知功能,按 MMSE 评估结果将患者分为 POCD 组和非 POCD 组进行分析。结果术后发生 POCD 患者共18例（22．5％）。2组术前1 d 血浆皮质醇水平比较差异无统计学意义（P ＞0．05）,POCD 组术后6 h、1 d、3 d、7 d 血浆皮质醇水平均明显高于术前1 d （P 均＜0．05）;非 POCD 组术后6 h、术后1 d 血浆皮质醇水平明显高于术前1 d （P 均＜0．05）,但术后3、7 d 血浆皮质醇水平与术前1 d 比较差异无统计学意义（P ＞0．05）;POCD 组术后6 h、1 d、3 d、7 d 血浆皮质醇水平均明显高于非 POCD 组（P均＜0．05）。POCD 组术后6 h、1 d、3 d、7 d MMSE 评分均明显低于术前1 d （P 均＜0．05）;非POCD 组术后6 h、术后1 d MMSE 评分明显低于术前1 d （P 均＜0．05）,但术后3、7 d MMSE 评分与术前1 d 比较差异无统计学意义（P 均＞0．05）;POCD 组术后6 h、1 d、3 d、7 d MMSE 评分均明显低于非 POCD 组（P 均＜0．05）。术后6 h、1 d、3 d、7 d 血浆皮质醇水平与 MMSE 评分均呈负相关（r 值分别为－0．674、－0．662、－0．635、－0．612,P 均＜0．05）。结论老年患者接受人工髋关节置换术后血浆皮质醇水平明显升高,这可能与其 POCD 的发生有关。     

Effect of Rehabilitation Program on Endocrinological Parameters in Patients with COPD and in Healthy Subjects

Background: Skeletal muscle wasting commonly occurs in patients with chronic obstructive pulmonary disease (COPD) and has been associated with the presence of systemic inflammation and endocrinological disturbance. The aim of this study is to analyze the effect of rehabilitation program on the balance of anabolic versus catabolic hormone in patients with COPD and in healthy subjects. Methods: Nineteen patients with COPD and 16 age-matched healthy subjects undertooked exercise training 3 days/week for 8 weeks. Before and after the training program the concentration of growth hormone (GH), Insulin-Like Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 3 (IGF-BP3), testosterone and cortisol in serum were determined. The exercise measurements included a 6-Minute Walking Test (6MWT). Results: After 8 weeks, there was no significant change in lung function in patients with COPD and healthy subjects. Growth hormone, Insulin-like Growth Factor-1 and Insulin-like Growth Factor-Binding Protein 3 increased significantly after rehabilitation training (p < 0.01). The rehabilitation program improves the testosterone/cortisol ratio (T/C ratio) in both groups. There is a significant improvement in the 6-Minute Walking distance (6MWD) in both groups (p < 0.01). Dyspnea and heart rate at rest and at the peak of the 6-Minute Walking Test (6MWT) decreased significantly after training program (p < 0.01). Conclusion: Pulmonary rehabilitation induces an improvement of the anabolic process and reduces proteine distruction by the modifications in endocrinological factors regulating skeletal muscle in patients with COPD.     

Speaking under pressure: Low linguistic complexity is linked to high physiological and emotional stress reactivity

What can a speech reveal about someone's state? We tested the idea that greater stress reactivity would relate to lower linguistic cognitive complexity while speaking. In Study 1, we tested whether heart rate and emotional stress reactivity to a stressful discussion would relate to lower linguistic complexity. In Studies 2 and 3, we tested whether a greater cortisol response to a standardized stressful task including a speech (Trier Social Stress Test) would be linked to speaking with less linguistic complexity during the task. We found evidence that measures of stress responsivity (emotional and physiological) and chronic stress are tied to variability in the cognitive complexity of speech. Taken together, these results provide evidence that our individual experiences of stress or “stress signatures”—how our body and mind react to stress both in the moment and over the longer term—are linked to how complex our speech under stress.     

宫内生长发育受限患儿血清糖皮质激素变化

目的探讨宫内生长发育受限患儿是否存在下丘脑一垂体一’肾上腺轴功能紊乱。方法收集2012-1-1至2013-6-1在北京友谊医院儿科住院的宫内生长发育受限（inttauterine growth re8triction,IUGR）患儿和适于胎龄儿（appropriate for gestational age,AGA）血清,采用ELISA方法检测血清促肾上腺皮质激素（ACTH）、皮质醇、醛固酮激素水平变化。结果IU6R48例,AGA50例,两组性别比无差异。IUGR血清ACTH、皮质醇浓度（均数±标准差）浓度均比AGA组明显升高,且差异有统计学意义（P〈0．05）;IUGR血清醛固酮浓度与AGA组相比,血清水平下降,但差异无统计学意义,P〉0．05。结论宫内生长发育受限患儿血清ACTH、皮质醇浓度均明显高于适于胎龄儿,提示宫内生长发育受限患儿存在下丘脑-垂体-肾上腺轴的功能紊乱。     

慢性阻塞性肺疾病急性加重期血清皮质醇的表达特征

目的探讨慢性阻塞性肺疾病急性加重期（AECOPD）血清皮质醇的表达特征。方法随机选取2011年10月至2012年10月在我院住院的AECOPD患者65例为COPD组,根据肺功能结果分为轻中度组33例及重度、极重度组32例,同期住院的非COPD患者33例为非COPD组。全部研究对象分别于人院后第二天的8am、4pm及0am三个时间段各抽取肘静脉血,分别检测血清皮质醇和促肾上腺皮质激素水平。结果三个不同时间段轻、中度组及重度、极重度组皮质醇水平明显低于非COPD组（P〈0．01）;8am时段轻、中度组明显低于重度、极重度组（P〈0．01）。三个不同时段轻、中度组及重度、极重度组促肾上腺皮质激素水平高于非COPD组（P〈0．05）。结论AECOPD患者存在肾上腺皮质代谢紊乱,表现为血清皮质醇水平降低,促肾上腺皮质激素水平升高。     

Tissue-specific modulation of mineralocorticoid receptor function by 11β-hydroxysteroid dehydrogenases: an overview

In the last decade significant progress has been made in the understanding of mineralocorticoid receptor (MR) function and its implications for physiology and disease. The knowledge on the essential role of MR in the regulation of electrolyte concentrations and blood pressure has been significantly extended, and the relevance of excessive MR activation in promoting inflammation, fibrosis and heart disease as well as its role in modulating neuronal cell viability and brain function is now widely recognized. Despite considerable progress, the mechanisms of MR function in various cell-types are still poorly understood. Key modulators of MR function include the glucocorticoid receptor (GR), which may affect MR function by formation of heterodimers and by differential genomic and non-genomic responses on gene expression, and 11β-hydroxysteroid dehydrogenases (11β-HSDs), which determine the availability of intracellular concentrations of active glucocorticoids. In this review we attempted to provide an overview of the knowledge on MR expression with regard to the presence or absence of GR, 11β-HSD2 and 11β-HSD1/hexose-6-phosphate dehydrogenase (H6PDH) in various tissues and cell types. The consequences of cell-specific differences in the coexpression of MR with these proteins need to be further investigated in order to understand the role of this receptor in a given tissue as well as its systemic impact.