Development of psychophysiological motoric reactivity is influenced by peripubertal pharmacological inhibition of gonadotropin releasing hormone action - Results of an ovine model

This study reports the effects of peripubertal GnRH receptor inactivation on development of psychophysiological motoric reactivity (PMR; sometimes also called emotional reactivity), plasma cortisol concentrations and the relationship between plasma cortisol and PMR in male and female sheep. The study formed part of a larger trial and utilised 46 same sex twins. One twin remained untreated (control) while the other received a subcutaneous GnRH agonist (GnRHa Goserelin-Acetate) implant every 4th week, beginning at 8 and 28 weeks of age, in males and females, respectively (different, due to sex specific age of puberty). PMR, a measure of an animals' response to social isolation, was measured over a two minute period at 8, 28 and 48 weeks of age, using a three axis accelerometer. During the test period vocalisation rate was recorded. Cortisol was assayed in blood samples collected on a single day when animals were 40 weeks of age. PMR and vocalisation rate were significantly higher in females than males at all ages tested. At 28 weeks of age (20 weeks treatment) PMR was increased in treated males to the level seen in control females, by 48 weeks of age treated males' PMR was significantly less than controls. In females, 20 weeks of GnRHa treatment (28-48 weeks of age) was not associated with differences in PMR. Cortisol concentrations were significantly higher in females than males but were not affected by treatment. Plasma cortisol concentrations were positively correlated with PMR; this relationship being driven by the treated animals in both sexes. The results demonstrate that PMR is sexually dimorphic and cortisol dependent in sheep from at least 8 weeks of age. Importantly, they also demonstrate that long-term treatment of males with a GnRH agonist results in changes in age-dependent development of PMR.     

The development of a rat in vitro model of spinal cord injury demonstrating the additive effects of Rho and ROCK inhibitors on neurite outgrowth and myelination

It is currently thought that treatment for spinal cord injury (SCI) will involve a combined pharmacological and biological approach; however, testing their efficacy in animal models of SCI is time-consuming and requires large animal cohorts. For this reason we have modified our myelinating cultures as an in vitro model of SCI and studied its potential as a prescreen for combined therapeutics. This culture comprises dissociated rat embryonic spinal cord cells plated onto a monolayer of astrocytes, which form myelinated axons interspaced with nodes of Ranvier. After cutting the culture, an initial cell-free area appears persistently devoid of neurites, accompanied over time by many features of SCI, including demyelination and reduced neurite density adjacent to the lesion, and infiltration of microglia and reactive astrocytes into the lesioned area. We tested a range of concentrations of the Rho inhibitor C3 transferase (C3) and ROCK inhibitor Y27632 that have been shown to promote SCI repair in vivo. C3 promoted neurite extension into the lesion and enhanced neurite density in surrounding areas but failed to induce remyelination. In contrast, while Y27632 did not induce significant neurite outgrowth, myelination adjacent to the lesion was dramatically enhanced. The effects of the inhibitors were concentration-dependent. Combined treatment with C3 and Y27632 had additive affects with an enhancement of neurite outgrowth and increased myelination adjacent to the lesion, demonstrating neither conflicting nor synergistic effects when coadministered. Overall, these results demonstrate that this culture serves as a useful tool to study combined strategies that promote CNS repair.     

两种气道湿化方法对气管切开术后病人的影响

目的:探讨两种气道湿化方法对气管切开术后病人的影响.方法:选择60例病人为研究对象,随机分为试验组与对照组各30例.试验组采用微泵持续向气道内滴注湿化液;对照组采用传统的间断气道湿化方法.结果:两组病人肺部感染、刺激性咳嗽发生率及气管套管拔管时间,差异有统计学意义(P＜0.05).结论:持续气道湿化能有效降低气管切开术后病人肺部感染的发生,减少病人刺激性咳嗽,缩短拔管时间,效果较好.     

Rumination relates to reduced autobiographical memory specificity in formerly depressed patients following a self-discrepancy challenge: the case of autobiographical memory specificity reactivity

Background and objectives

Reduced Autobiographical Memory Specificity (rAMS) is a hypothesized vulnerability factor for depression. Rumination is thought to be one of the processes underlying rAMS, but research has failed to show an association between trait rumination and rAMS in individuals who are not currently depressed (e.g., community samples, college samples, and formerly depressed samples). The present study tested whether a challenge procedure that induces a self-discrepancy focus can elicit an association between trait rumination and rAMS in formerly depressed participants.

Methods

Trait rumination was assessed via self-report. Measures of psychopathology and cognitive function, including depression, were assessed via self-report and interview. Autobiographical Memory Specificity (AMS) was evaluated before and after the induction of a self-discrepancy focus in formerly depressed participants.

Results

Results showed that trait rumination was indeed negatively correlated with AMS after, but not before the induction. Moreover, high trait ruminating participants showed a decrease in AMS following the induction. In other words, memory specificity was reactive to the induction, but no such decrease was observed in low trait ruminating individuals.

Limitations

This study is mostly of women. These results may not generalize well to men. Our experimental control was within-subjects, which, although powerful and economical, cannot rule out certain confounding processes including natural changes in self-discrepancy, or non-specific or unintended effects of the induction.

Conclusions

In order to detect rAMS in formerly depressed individuals or to observe associations between rAMS and trait measures of rumination, state ruminative processing needs to be activated. Results are discussed by framing rAMS as an example of cognitive reactivity, a general type of processing that is associated with depression.     

脑梗死患者脑血管反应性研究

目的应用经颅多普勒超声结合屏气试验评价脑梗死患者的脑血管反应性（CVR）。方法采用经颅多普勒超声结合屏气试验检测30例急性期颈内动脉系统脑梗死患者,30例急性期腔隙性脑梗死患者的屏气指数（BHI）,并与60例健康者进行对比。结果急性期颈内动脉系统脑梗死患者和腔隙性脑梗死患者屏气指数均显著低于对照组,颈内动脉系统脑梗死侧显著低于对侧和腔隙性脑梗死患者。结论脑血管反应性与脑梗死有密切关系,检测脑血管反应性对于预测脑卒中风险至关重要。     

Exome-chip meta-analysis identifies association between variation in ANKRD26 and platelet aggregation

Previous genome-wide association studies (GWAS) have identified several variants associated with platelet function phenotypes; however, the proportion of variance explained by the identified variants is mostly small. Rare coding variants, particularly those with high potential for impact on protein structure/function, may have substantial impact on phenotype but are difficult to detect by GWAS. The main purpose of this study was to identify low frequency or rare variants associated with platelet function using genotype data from the Illumina HumanExome Bead Chip. Three family-based cohorts of European ancestry, including ~4,000 total subjects, comprised the discovery cohort and two independent cohorts, one of European and one of African American ancestry, were used for replication. Optical aggregometry in platelet-rich plasma was performed in all the discovery cohorts in response to adenosine diphosphate (ADP), epinephrine, and collagen. Meta-analyses were performed using both gene-based and single nucleotide variant association methods. The gene-based meta-analysis identified a significant association (P = 7.13 × 10^–7) between rare genetic variants in ANKRD26 and ADP-induced platelet aggregation. One of the ANKRD26 SNVs - rs191015656, encoding a threonine to isoleucine substitution predicted to alter protein structure/function, was replicated in Europeans. Aggregation increases of ~20–50% were observed in heterozygotes in all cohorts. Novel genetic signals in ABCG1 and HCP5 were also associated with platelet aggregation to ADP in meta-analyses, although only results for HCP5 could be replicated. The SNV in HCP5 intersects epigenetic signatures in CD41+ megakaryocytes suggesting a new functional role in platelet biology for HCP5. This is the first study to use gene-based association methods from SNV array genotypes to identify rare variants related to platelet function. The molecular mechanisms and pathophysiological relevance for the identified genetic associations requires further study.     

Comparison of factors affecting platelet reactivity in various platelet function tests

Previous studies have reported that various factors affect ADP-induced platelet reactivity during clopidogrel therapy. The aim of this study was to determine whether clinical and laboratory variables for platelet reactivity during dual antiplatelet therapy (DAPT) are dependent on the assay used. We enrolled 904 patients receiving DAPT following coronary intervention. Platelet reactivity was measured using three methods: the VerifyNow P2Y12 assay, multiple electrode aggregometry (MEA) ADP assay, and the light transmittance aggregometry (LTA) ADP assay at 24–48 h following coronary intervention. The VerifyNow results demonstrated a significant inverse correlation with hematocrit value (r = –0.268, p < 0.0001); however, MEA results had no such correlation with hematocrit (r = 0.044, p = 0.188). There was a positive correlation between the MEA results and platelet count (r = 0.255, p < 0.0001). LTA was weakly influenced by hematocrit (r = –0.064, p = 0.057) and platelet count (r = 0.069, p = 0.040). Gender (odds ratio 1.53, 95% CI 1.10–2.14, p = 0.013) and hematocrit (odds ratio 0.91,95% CI 0.88–0.94, p < 0.0001) were the independent variables for HPR by VerifyNow. Smoking (odds ratio 0.38, 95% CI 0.16–0.94, p = 0.036) and platelet count (odds ratio 1.01, 95% CI 1.00–1.01, p < 0.0001) were independent factors for HPR when using the MEA assay, whereas platelet count (odds ratio 1.00, 95% CI 1.00–1.01, p = 0.006) was identified as the only independent variable for HPR when using LTA. The incidence of HPR and the influencing variables involved are dependent on the platelet function test used.     

黄连素对COPD大鼠气道炎症和粘液高分泌的调控作用研究

目的探讨黄连素对COPD大鼠气道炎症和粘液高分泌的影响及研究其相关分子机制。方法清洁级雄性Wistar大鼠随机分为生理盐水对照组、COPD模型组和黄连素组各10只,通过熏香烟加气管注内毒素方法建立大鼠COPD模型。采集支气管肺泡灌洗液用ELISA法检测中性粒细胞弹性蛋白酶（neutrophil elastase,NE）、IL-10含量。采集支气管-肺组织标本用免疫组织化学法（SP法）检测NF-κB、粘蛋白Muc5ac表达,采用逆转录-聚合酶链反应（RT-PCR）检测Muc5ac mRNA表达。结果 COPD模型组大鼠BALF细胞总数、中性粒细胞数（PMN）、巨噬细胞数（AM）、NE较正常对照组显著升高（P〈0.01）,IL-10水平显著下降（P〈0.01）。黄连素组BALF细胞总数、PMN、AM较COPD组显著降低（P〈0.01）,L-10水平升则高（P〈0.05）。COPD模型组大鼠气道黏膜上皮NF-κB、Muc5ac mRN及蛋白表达较正常对照组显著升高（P〈0.01）。黄连素组气道黏膜上皮NF-κB、Muc5ac mRN及蛋白表达较COPD组显著下降（P〈0.01）。结论黄连素可负向调节气道炎症和粘液高分泌,其机制可能与黄连素抑制NE、NF-κB炎症因子,促进抗炎因子IL-10,下调粘蛋白Muc5ac表达有关。