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Circulating elastin peptides, role in vascular pathology 循环弹性蛋白肽,在血管病理中的作用
Pub Date : 2014-12-01 DOI: 10.1016/j.patbio.2014.05.020
L. Robert, J. Labat-Robert

The atherosclerotic process starts with the degradation of elastic fibers. Their presence was demonstrated in the circulation as well as several of their biological properties elucidated. We described years ago a procedure to obtain large elastin peptides by organo-alkaline hydrolysis, κ-elastin. This method enabled also the preparation of specific antibodies used to determine elastin peptides, as well as anti-elastin antibodies in body fluids and tissue extracts. Elastin peptides were determined in a large number of human blood samples. Studies were carried out to explore their pharmacological properties. Similar recent studies by other laboratories confirmed our findings and arose new interest in circulating elastin peptides for their biological activities. This recent trend justified the publication of a review of the biological and pathological activities of elastin peptides demonstrated during our previous studies, subject of this article.

动脉粥样硬化过程始于弹性纤维的降解。它们在循环中存在,并阐明了它们的一些生物学特性。多年前,我们描述了一种通过有机碱性水解获得大弹性蛋白肽的方法,即κ-弹性蛋白。该方法还可以制备用于测定体液和组织提取物中弹性蛋白肽以及抗弹性蛋白抗体的特异性抗体。在大量人体血液样本中测定了弹性蛋白肽。对其药理特性进行了研究。其他实验室最近的类似研究证实了我们的发现,并对循环弹性蛋白肽的生物活性产生了新的兴趣。这一最近的趋势证明了在我们之前的研究中所证明的弹性蛋白肽的生物学和病理活性的评论的出版是合理的,这篇文章的主题。
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引用次数: 6
High level of reactive oxygen species impaired mesenchymal stem cell migration via overpolymerization of F-actin cytoskeleton in systemic lupus erythematosus 在系统性红斑狼疮中,高水平的活性氧通过f -肌动蛋白细胞骨架的过度聚合损害了间充质干细胞的迁移
Pub Date : 2014-12-01 DOI: 10.1016/j.patbio.2014.07.009
D. Shi , X. Li , H. Chen , N. Che , S. Zhou , Z. Lu , S. Shi , L. Sun

Some lines of evidence have demonstrated abnormalities of bone marrow mesenchymal stem cells (MSCs) in systemic lupus erythematosus (SLE) patients, characterized by defective phenotype of MSCs and slower growth with enhanced apoptosis and senescence. However, whether SLE MSCs demonstrate aberrant migration capacity or abnormalities in cytoskeleton are issues that remain poorly understood. In this study, we found that MSCs from SLE patients did show impairment in migration capacity as well as abnormalities in F-actin cytoskeleton, accompanied by a high level of intracellular reactive oxygen species (ROS). When normal MSCs were treated in vitro with H2O2, which increases intracellular ROS level as an oxidant, both reorganization of F-actin cytoskeleton and impairment of migration capability were observed. On the other hand, treatment with N-acetylcysteine (NAC), as an exogenous antioxidant, made F-actin more orderly and increased migration ratio in SLE MSCs. In addition, oral administration of NAC markedly reduced serum autoantibody levels and ameliorated lupus nephritis (LN) in MRL/lpr mice, partially reversing the abnormalities of MSCs. These results indicate that overpolymerization of F-actin cytoskeleton, which may be associated with high levels of ROS, causes impairment in the migration capacity of SLE MSCs and that oral administration of NAC may have potential therapeutic effects on MRL/lpr mice.

一些证据表明,系统性红斑狼疮(SLE)患者骨髓间充质干细胞(MSCs)异常,其特征是MSCs表型缺陷,生长缓慢,细胞凋亡和衰老增强。然而,SLE间充质干细胞是否表现出异常的迁移能力或细胞骨架的异常,仍然是一个知之甚少的问题。在这项研究中,我们发现来自SLE患者的MSCs确实表现出迁移能力受损以及f -肌动蛋白细胞骨架异常,并伴有高水平的细胞内活性氧(ROS)。H2O2作为氧化剂增加细胞内ROS水平,在体外处理正常间充质干细胞时,观察到f -肌动蛋白细胞骨架重组和迁移能力受损。另一方面,n -乙酰半胱氨酸(NAC)作为外源性抗氧化剂,使F-actin在SLE间充质干细胞中更加有序并增加迁移率。此外,口服NAC可显著降低MRL/lpr小鼠的血清自身抗体水平,改善狼疮性肾炎(LN),部分逆转MSCs的异常。这些结果表明,可能与高水平ROS相关的f -肌动蛋白细胞骨架的过度聚合导致SLE MSCs迁移能力受损,口服NAC可能对MRL/lpr小鼠具有潜在的治疗作用。
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引用次数: 31
Sleep regulation and sex hormones exposure in men and women across adulthood 成年期男性和女性的睡眠调节和性激素暴露
Pub Date : 2014-10-01 DOI: 10.1016/j.patbio.2014.07.005
C. Lord , Z. Sekerovic , J. Carrier

This review aims to discuss how endogenous and exogenous testosterone exposures in men and estrogens/progesterone exposures in women interact with sleep regulation. In young men, testosterone secretion peaks during sleep and is linked to sleep architecture. Animal and human studies support the notion that sleep loss suppresses testosterone secretion. Testosterone levels decline slowly throughout the aging process, but relatively few studies investigate its impact on age-related sleep modifications. Results suggest that poorer sleep quality is associated with lower testosterone concentrations and that sleep loss may have a more prominent effect on testosterone levels in older individuals. In women, sex steroid levels are characterized by a marked monthly cycle and reproductive milestones such as pregnancy and menopause. Animal models indicate that estrogens and progesterone influence sleep. Most studies do not show any clear effects of the menstrual cycle on sleep, but sample sizes are too low, and research designs often inhibit definitive conclusions. The effects of hormonal contraceptives on sleep are currently unknown. Pregnancy and the postpartum period are associated with increased sleep disturbances, but their relation to the hormonal milieu still needs to be determined. Finally, studies suggest that menopausal transition and the hormonal changes associated with it are linked to lower subjective sleep quality, but results concerning objective sleep measures are less conclusive. More research is necessary to unravel the effects of vasomotor symptoms on sleep. Hormone therapy seems to induce positive effects on sleep, but key concerns are still unresolved, including the long-term effects and efficacy of different hormonal regimens.

本综述旨在讨论男性内源性和外源性睾酮暴露以及女性雌激素/孕酮暴露如何与睡眠调节相互作用。在年轻男性中,睾酮分泌在睡眠期间达到峰值,并与睡眠结构有关。动物和人体研究支持睡眠不足会抑制睾丸激素分泌的观点。睾酮水平在整个衰老过程中缓慢下降,但相对较少的研究调查了它对与年龄相关的睡眠改变的影响。研究结果表明,较差的睡眠质量与较低的睾酮浓度有关,而睡眠不足可能对老年人的睾酮水平有更显著的影响。在女性中,性类固醇水平的特点是有明显的月经周期和生育里程碑,如怀孕和更年期。动物模型表明雌激素和黄体酮会影响睡眠。大多数研究并没有显示月经周期对睡眠有任何明确的影响,但样本量太小,而且研究设计往往会抑制明确的结论。激素避孕药对睡眠的影响目前尚不清楚。怀孕和产后与睡眠障碍增加有关,但它们与激素环境的关系仍有待确定。最后,研究表明,更年期过渡和与此相关的激素变化与较低的主观睡眠质量有关,但有关客观睡眠测量的结果则不那么确凿。需要更多的研究来阐明血管舒缩症状对睡眠的影响。激素疗法似乎能对睡眠产生积极影响,但关键问题仍未解决,包括不同激素疗法的长期影响和疗效。
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引用次数: 67
Analgésie placebo et sommeil 安慰剂镇痛和睡眠
Pub Date : 2014-10-01 DOI: 10.1016/j.patbio.2014.07.001
F. Chouchou , G.-J. Lavigne

The placebo response is a psychobiological phenomenon for clinical benefits following the administration of an inert substance whatever its form. This phenomenon can be attributed to a wide range of neurobiological processes, such as expectations of relief, the Pavlovian conditioning and learning, emotional regulation, and reward mechanisms, which are themselves under the influence of processes that take place during sleep. The study of placebo analgesia in healthy from a placebo conditioning associated with analgesic suggestions has highlighted a relationship between sleep, expectations of relief and placebo analgesia: when the induction is persuasive before sleep, expectations of relief modulate placebo response the next morning and paradoxical sleep correlates negatively with both expectations and the placebo response. When the analgesic experience before sleep is less persuasive, expectations of relief are still present but no longer interact with placebo analgesia while paradoxical sleep no longer correlates with the analgesic placebo response. Sleep-processes especially during paradoxical sleep seem to influence the relationship between expectations of relief and placebo analgesia. In this review, we describe the relationship between sleep and placebo analgesia, the mechanisms involved in the placebo response (e.g., conditioning, learning, memory, reward) and their potential link with sleep that could make it a special time for the building placebo response.

安慰剂反应是一种心理生物学现象,在给予任何形式的惰性物质后都有临床益处。这种现象可以归因于广泛的神经生物学过程,如缓解预期、巴甫洛夫条件反射和学习、情绪调节和奖励机制,这些过程本身都受到睡眠过程的影响。在健康的安慰剂条件作用下,与镇痛建议相关的安慰剂镇痛研究强调了睡眠、缓解预期和安慰剂镇痛之间的关系:当睡前诱导具有说服力时,缓解预期调节第二天早上的安慰剂反应,而矛盾睡眠与预期和安慰剂反应均呈负相关。当睡前的镇痛体验不那么有说服力时,缓解的期望仍然存在,但不再与安慰剂镇痛相互作用,而矛盾睡眠不再与镇痛安慰剂反应相关。睡眠过程,特别是在矛盾睡眠期间,似乎影响缓解预期和安慰剂镇痛之间的关系。在这篇综述中,我们描述了睡眠和安慰剂镇痛之间的关系,安慰剂反应的机制(如条件反射、学习、记忆、奖励)以及它们与睡眠的潜在联系,这些联系可能使睡眠成为建立安慰剂反应的特殊时间。
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引用次数: 5
The effect of sleep restriction on neurobehavioural functioning in normally developing children and adolescents: Insights from the attention behaviour and sleep laboratory 睡眠限制对正常发育儿童和青少年神经行为功能的影响:来自注意力行为和睡眠实验室的见解
Pub Date : 2014-10-01 DOI: 10.1016/j.patbio.2014.05.017
J. Cassoff , J.A. Bhatti , R. Gruber

In the current paper, we first introduce the research themes of the attention, behaviour and sleep (ABS) laboratory, namely, sleep and ADHD, sleep and obesity, and sleep and academic performance. We then focus in on the topic to be reviewed in the current paper – the association between sleep restriction and neurobehavioral functioning (NBF) in typically developing children. We review the research thus far conducted by the ABS lab specific to this topic and posit the unique methodological contributions of the ABS lab (e.g. home-based assessment of sleep architecture and patterns, extensive phenotyping, etc.) in terms of advancing this research area. In the second section of the paper, we review 13 studies investigating the causal association between experimental sleep restriction and NBF in normally developing pediatric populations. Eight of the 13 studies found that sleep restriction causes impairments in neurobehavioural functioning. However, given the inconsistency in outcome measures, experimental protocols and statistical power, the studies reviewed herein are difficult to interpret. Strategies used by the ABS including implementing home assessments of sleep, restricting sleep relative to the participants’ typical sleep schedules, blinding raters who assess NBF, and using valid and reliable NBF assessments are an attempt to address the gaps in this research area and clarify the causal relationship between sleep restriction and NBF in typically developing children and adolescents.

在本文中,我们首先介绍了注意,行为和睡眠(ABS)实验室的研究主题,即睡眠与多动症,睡眠与肥胖,睡眠与学习成绩。然后,我们将重点放在本文将要回顾的主题上——睡眠限制与正常发育儿童神经行为功能(NBF)之间的关系。我们回顾了ABS实验室迄今为止针对这一主题进行的研究,并假设ABS实验室在推进这一研究领域方面的独特方法贡献(例如,基于家庭的睡眠结构和模式评估,广泛的表型分析等)。在论文的第二部分,我们回顾了13项研究,调查了正常发育的儿科人群中实验性睡眠限制与NBF之间的因果关系。13项研究中有8项发现,睡眠不足会导致神经行为功能受损。然而,考虑到结果测量、实验方案和统计能力的不一致性,本文综述的研究难以解释。ABS采用的策略包括实施家庭睡眠评估,相对于参与者的典型睡眠时间表限制睡眠,对评估NBF的评分者进行盲化,以及使用有效可靠的NBF评估,这些都是试图解决这一研究领域的空白,并阐明典型发育儿童和青少年睡眠限制与NBF之间的因果关系。
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引用次数: 17
Impacts of shift work on sleep and circadian rhythms 轮班工作对睡眠和昼夜节律的影响
Pub Date : 2014-10-01 DOI: 10.1016/j.patbio.2014.08.001
D.B. Boivin, P. Boudreau

Shift work comprises work schedules that extend beyond the typical “nine-to-five” workday, wherein schedules often comprise early work start, compressed work weeks with 12-hour shifts, and night work. According to recent American and European surveys, between 15 and 30% of adult workers are engaged in some type of shift work, with 19% of the European population reportedly working at least 2 hours between 22:00 and 05:00. The 2005 International Classification of Sleep Disorders estimates that a shift work sleep disorder can be found in 2–5% of workers. This disorder is characterized by excessive sleepiness and/or sleep disruption for at least one month in relation with the atypical work schedule. Individual tolerance to shift work remains a complex problem that is affected by the number of consecutive work hours and shifts, the rest periods, and the predictability of work schedules. Sleepiness usually occurs during night shifts and is maximal at the end of the night. Impaired vigilance and performance occur around times of increased sleepiness and can seriously compromise workers’ health and safety. Indeed, workers suffering from a shift work sleep-wake disorder can fall asleep involuntarily at work or while driving back home after a night shift. Working on atypical shifts has important socioeconomic impacts as it leads to an increased risk of accidents, workers’ impairment and danger to public safety, especially at night. The aim of the present review is to review the circadian and sleep-wake disturbances associated with shift work as well as their medical impacts.

轮班工作包括超出典型的“朝九晚五”工作日的工作安排,其中通常包括提前开始工作,12小时轮班的压缩工作周以及夜间工作。根据最近美国和欧洲的调查,15%到30%的成年工人从事某种类型的倒班工作,19%的欧洲人口据报道在22:00到05:00之间工作至少2小时。2005年《国际睡眠障碍分类》估计,2-5%的工人患有轮班工作睡眠障碍。这种疾病的特点是过度嗜睡和/或睡眠中断至少一个月,与非典型的工作时间表有关。个人对轮班工作的容忍度仍然是一个复杂的问题,它受到连续工作时间和班次、休息时间和工作时间表可预测性的影响。困倦通常发生在夜班期间,在晚上结束时最为严重。警觉性和工作表现受损通常发生在睡意增加的时候,并可能严重损害工人的健康和安全。事实上,患有倒班工作睡眠-觉醒障碍的员工可能会在工作中或夜班后开车回家时不由自主地睡着。非典型轮班工作具有重要的社会经济影响,因为它会导致事故风险增加,工人受伤和公共安全危险,特别是在夜间。本综述的目的是回顾与轮班工作相关的昼夜节律和睡眠觉醒障碍及其医学影响。
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引用次数: 367
Kind attention and non-judgment in mindfulness-based cognitive therapy applied to the treatment of insomnia: State of knowledge 正念认知疗法在失眠治疗中的应用:认知状态
Pub Date : 2014-10-01 DOI: 10.1016/j.patbio.2014.07.002
M. Larouche , G. Côté , D. Bélisle , D. Lorrain

Psychophysiological insomnia is characterized by acquired sleep difficulties and/or a state of hypervigilance when going to bed. This mental and physiological condition prevents sleep onset regardless of the presence of anxious or depressive disorders. Despite the fact that cognitive behavioural therapies have been shown to be effective for this disorder, some people are not responding to this treatment. It is therefore important to explore new ways of increasing the effectiveness of current treatments. Approaches based on mindfulness, which promote a non-judgemental acceptance of the living experience, are increasingly reported in the literature to be effective in the treatment of various physical and psychological health conditions, being particularly efficient in reducing the stress and discomfort associated with these problems. This article focuses on some cognitive factors associated with maintaining insomnia and suggests that approaches based on mindfulness, through certain action mechanisms, may help to improve sleep. A review of recent studies on the application of mindfulness-based approaches to treat insomnia is hereby presented. Avenues for future research to improve insomnia treatment protocols based on mindfulness are suggested.

心理生理性失眠的特点是获得性睡眠困难和/或睡觉时高度警惕。无论是否存在焦虑或抑郁障碍,这种精神和生理状况都会阻止睡眠的发生。尽管事实证明认知行为疗法对这种疾病有效,但有些人对这种治疗没有反应。因此,探索提高当前治疗效果的新方法是很重要的。基于正念的方法促进对生活经验的非评判性接受,文献中越来越多地报道,这种方法在治疗各种身心健康状况方面是有效的,在减少与这些问题相关的压力和不适方面尤其有效。这篇文章的重点是一些与失眠相关的认知因素,并建议基于正念的方法,通过某些作用机制,可能有助于改善睡眠。现就正念疗法治疗失眠的最新研究作一综述。提出了基于正念的失眠治疗方案的未来研究方向。
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引用次数: 20
The role of sleep and circadian rhythms in health: A snapshot of key research interrogations 睡眠和昼夜节律在健康中的作用:关键研究询问的快照
Pub Date : 2014-10-01 DOI: 10.1016/j.patbio.2014.09.001
J. Carrier
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引用次数: 5
Cognitive impairment in obstructive sleep apnea 阻塞性睡眠呼吸暂停的认知障碍
Pub Date : 2014-10-01 DOI: 10.1016/j.patbio.2014.05.015
K. Gagnon , A.-A. Baril , J.-F. Gagnon , M. Fortin , A. Décary , C. Lafond , A. Desautels , J. Montplaisir , N. Gosselin

Obstructive sleep apnea (OSA) is characterised by repetitive cessation or reduction of airflow due to upper airway obstructions. These respiratory events lead to chronic sleep fragmentation and intermittent hypoxemia. Several studies have shown that OSA is associated with daytime sleepiness and cognitive dysfunctions, characterized by impairments of attention, episodic memory, working memory, and executive functions. This paper reviews the cognitive profile of adults with OSA and discusses the relative role of altered sleep and hypoxemia in the aetiology of these cognitive deficits. Markers of cognitive dysfunctions such as those measured with waking electroencephalography and neuroimaging are also presented. The effects of continuous positive airway pressure (CPAP) on cognitive functioning and the possibility of permanent brain damage associated with OSA are also discussed. Finally, this paper reviews the evidence suggesting that OSA is a risk factor for developing mild cognitive impairment and dementia in the aging population and stresses the importance of its early diagnosis and treatment.

阻塞性睡眠呼吸暂停(OSA)的特征是由于上呼吸道阻塞而反复停止或减少气流。这些呼吸事件导致慢性睡眠中断和间歇性低氧血症。一些研究表明,阻塞性睡眠呼吸暂停与白天嗜睡和认知功能障碍有关,其特征是注意力、情景记忆、工作记忆和执行功能受损。本文综述了阻塞性睡眠呼吸暂停成人的认知概况,并讨论了睡眠改变和低氧血症在这些认知缺陷病因学中的相对作用。认知功能障碍的标志,如那些测量醒脑电图和神经影像学也提出。持续气道正压通气(CPAP)对认知功能的影响以及与OSA相关的永久性脑损伤的可能性也进行了讨论。最后,本文综述了OSA是老年人发生轻度认知障碍和痴呆的危险因素的证据,并强调了早期诊断和治疗的重要性。
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引用次数: 180
Insomnia and sleep misperception 失眠和睡眠错觉
Pub Date : 2014-10-01 DOI: 10.1016/j.patbio.2014.07.003
C.H. Bastien , T. Ceklic , P. St-Hilaire , F. Desmarais , A.D. Pérusse , J. Lefrançois , M. Pedneault-Drolet

Sleep misperception is often observed in insomnia individuals (INS). The extent of misperception varies between different types of INS. The following paper comprised sections which will be aimed at studying the sleep EEG and compares it to subjective reports of sleep in individuals suffering from either psychophysiological insomnia or paradoxical insomnia and good sleeper controls. The EEG can be studied without any intervention (thus using the raw data) via either PSG or fine quantitative EEG analyses (power spectral analysis [PSA]), identifying EEG patterns as in the case of cyclic alternating patterns (CAPs) or by decorticating the EEG while scoring the different transient or phasic events (K-Complexes or sleep spindles). One can also act on the on-going EEG by delivering stimuli so to study their impact on cortical measures as in the case of event-related potential studies (ERPs). From the paucity of studies available using these different techniques, a general conclusion can be reached: sleep misperception is not an easy phenomenon to quantify and its clinical value is not well recognized. Still, while none of the techniques or EEG measures defined in the paper is available and/or recommended to diagnose insomnia, ERPs might be the most indicated technique to study hyperarousal and sleep quality in different types of INS. More research shall also be dedicated to EEG patterns and transient phasic events as these EEG scoring techniques can offer a unique insight of sleep misperception.

在失眠个体(INS)中经常观察到睡眠错觉。误解的程度因不同类型的INS而异。下面的论文将包括几个部分,旨在研究睡眠脑电图,并将其与患有心理生理性失眠或矛盾性失眠和良好睡眠控制的个体的主观睡眠报告进行比较。通过PSG或精细的定量脑电图分析(功率谱分析[PSA]),可以在没有任何干预的情况下(因此使用原始数据)研究脑电图,识别周期性交替模式(CAPs)的脑电图模式,或者在对不同的瞬态或阶段性事件(k -复合体或睡眠纺锤波)进行评分时对脑电图进行去皮。在事件相关电位研究(event- relevant potential studies, ERPs)中,人们也可以通过传递刺激来作用于正在进行的脑电图,以研究它们对皮层测量的影响。从使用这些不同技术的可用研究的缺乏来看,可以得出一个总的结论:睡眠错觉不是一个容易量化的现象,其临床价值也没有得到很好的认识。然而,虽然论文中定义的技术或脑电图测量方法都不能用于诊断失眠,或推荐用于诊断失眠,但erp可能是研究不同类型INS中过度觉醒和睡眠质量的最有效技术。更多的研究还应致力于脑电图模式和瞬态相事件,因为这些脑电图评分技术可以为睡眠错觉提供独特的见解。
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引用次数: 51
期刊
Pathologie-biologie
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