骨髓基质干细胞心肌化诱导过程中转录因子NKx 2.5的表达

目的：研究5-氮杂胞嘧啶(5-azacytidine，5-aza)和二甲亚砜(dimethyl sulfoxide．DMSO)诱导人骨髓基质细胞(human bone marrow stromal cells，hBMSC)心肌分化过程中心肌特异转录因子NKx2.5表达的变化。方法：取传至第8代hM-SC，以3μmol/L的5-aza和DMSO诱导24h。1周后重复诱导1次。在诱导后1、2和3周3个时间点以半定量RT-PCR方法检测细胞心肌特异转录因子NKx2.5的表达变化。结果：hMSC经5-aza诱导后，约1周左右细胞明显变大，2周时细胞走向趋于一致．邻近细胞间连接较前紧密，并形成肌节样结构。RT-PCR的结果显示，5-aza可诱导心肌特异转录因子NKx2.5，并一直持续表达3周。在DMSO诱导hBMSC后1周，开始可检测到细胞发生转录水平变化NKx2.5表达，并均可持续表达至诱导后3周；NKx2.5表达量有随诱导后时间延长而增加的趋势。结论：5-aza和DMSO在体外可诱导心肌特异转录因子NKx2.5的表达，从而启动hMSC心肌化的过程。     

五常法在手术室腹腔镜管理中的应用

目的:探讨确保腹腔镜手术的顺利进行,提高手术质量,延长设备、器械使用寿命的方法。方法:总结我院自1993年3月开展腹腔镜手术以来,五常法在手术室腹腔镜管理中的应用情况。结果:无一例因腹腔镜器械故障或欠缺而影响手术的顺利进行。结论:五常法的应用减少了手术护理工作中的缺陷,增强了手术室护士工作的主动性和计划性,增强了手术护士的工作成就感。     

Serotonin dynamics in and around the central nervous system: Is autism solvable without fundamental insights?

Altered serotonin (5-hydroxytryptamine, 5-HT) signaling has been implicated in some developmental abnormalities of autism spectrum disorder (ASD). However, the presumed role of 5-HT in ASD raises new questions in fundamental neuroscience. Specifically, it is not clear if the current piecemeal approach to 5-HT signaling in the mammalian body is effective and whether new conceptual approaches may be required. This review briefly discusses 5-HT production and circulation in the central nervous system and outside of it, especially with regard to ASD, and proposes a more encompassing approach that questions the utility of the “neurotransmitter” concept. It then introduces the idea of a generalized 5-HT packet that may offer insights into possible links between serotonergic varicosities and blood platelets. These approaches have theoretical significance, but they are also well positioned to advance our understanding of some long-standing problems in autism research.     

Axe I,Axe II ou Troubles mentaux et Troubles de la personnalité

Objectives

Since the publication of the third edition of the American classification the Diagnostic and Statistical Manual of mental disorders (DSM-III), psychiatric clinical syndromes and personality disorders appear in two distinct axes, axis I and II. In the fifth revision of the manual (DSM-5), published in May 2013, this distinction no longer exists and personality disorders now appear among other mental disorders. The aim of this paper is to try to pinpoint the clinical and epistemological stakes therein.

Method

The particular interest of this distinction was to attract the attention of the practitioners on the personality of the patients, independently of their psychiatric diagnoses. However today, its scientific justification appears insufficient. Numerous arguments are in favour of a continuity between the two axes and the nosographical reorganisation of anxiety, depression and personality disorders. This clarification summarises the principle tendencies that have emerged over the past ten years regarding the classification of personality disorders, with increasing dissatisfaction with the traditional categorical model and a growing interest in a dimensional perspective. These tendencies are illustrated by the recommendations drawn up by the DSM-5 task force on personality and personality disorders.

Results

The criticisms of the scientific world regarding theses recommendations have been strong. This article summarises the main arguments developed here and there, and the evolution of the task force's reflections up to the final decisions that were published in December 2012. No real consensus exists on the best dimensional model to be retained; even if the system most studied is, without doubt, the five-factor model, known as the ‘Big Five’.

Discussion

This system was studied above all in psychology, and its applicability to psychopathology, which could obviously be envisaged, requires adjustments and further validation studies before being finally adopted.

Conclusion

The return to a single axis perspective for personality disorders also justifies in depth reflection on the limits of normality and on the general definition of a mental disorder that has never been the subject of a true consensus in our profession.     

Control over a stressor involves the posterior dorsal striatum and the act/outcome circuit

Controllable/escapable tailshocks (ESs) do not produce the behavioral and neurochemical outcomes produced by equal yoked uncontrollable/inescapable tailshocks (ISs). The prelimbic cortex is known to play a key role in mediating the protective effects of control. The concepts of act/outcome learning and control seem similar, and act/outcome learning is mediated by a circuit involving the prelimbic cortex and posterior dorsomedial striatum (DMS). Thus, we tested the involvement of the DMS in the protective effect of ES, in rats. First, we examined Fos immunoreactivity in both the DMS and dorsolateral striatum (DLS) after ES and yoked IS. We then investigated the effect of blocking DMS or DLS N‐methyl‐d ‐aspartate receptors with the specific antagonist D‐(‐)‐2‐amino‐5‐phosphopentanoic acid (D‐AP5) on the release of dorsal raphe nucleus serotonin (5‐HT) during ES, as well as on the level of anxiety produced by the ES experience 24 h later. ES, but not yoked IS, produced a large increase of Fos activity in the DMS. Consistent with the Fos data, D‐AP5 in the DMS, but not in the DLS, prevented the inhibition of dorsal raphe nucleus 5‐HT release normally produced by ES. Furthermore, D‐AP5 administered into the DMS before ES, but not into the DLS, increased anxiety 24 h later, leading to levels similar to those produced by IS. These results suggest that, as with appetitive act/outcome contingency learning, the protective effects of behavioral control over a stressor require the DMS.     

Collapsin response‐mediator protein 5 (CRMP5) phosphorylation at threonine 516 regulates neurite outgrowth inhibition

The collapsin response‐mediator proteins (CRMPs) are multifunctional proteins highly expressed during brain development but down‐regulated in the adult brain. They are involved in axon guidance and neurite outgrowth signalling. Among these, the intensively studied CRMP2 has been identified as an important actor in axon outgrowth, this activity being correlated with the reorganisation of cytoskeletal proteins via the phosphorylation state of CRMP2. Another member, CRMP5, restricts the growth‐promotional effects of CRMP2 by inhibiting dendrite outgrowth at early developmental stages. This inhibition occurs when CRMP5 binds to tubulin and the microtubule‐associated protein MAP2, but the role of CRMP5 phosphorylation is still unknown. Here, we have studied the role of CRMP5 phosphorylation by mutational analysis. Using non‐phosphorylatable truncated constructs of CRMP5 we have demonstrated that, among the four previously identified CRMP5 phosphorylation sites (T509, T514, T516 and S534), only the phosphorylation at T516 residue was needed for neurite outgrowth inhibition in PC12 cells and in cultured C57BL/6J mouse hippocampal neurons. Indeed, the expression of the CRMP5 non‐phosphorylated form induced a loss of function of CRMP5 and the mutant mimicking the phosphorylated form induced the growth inhibition function seen in wildtype CRMP5. The T516 phosphorylation was achieved by the glycogen synthase kinase‐3β (GSK‐3β), which can phosphorylate the wildtype protein but not the non‐phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin‐binding property of CRMP5. Therefore, CRMP5‐induced growth inhibition is dependent on T516 phosphorylation through the GSK‐3β pathway. The findings provide new insights into the mechanisms underlying neurite outgrowth.     

The effects of prednisone and steroid-sparing agents on decay accelerating factor (CD55) expression: Implications in myasthenia gravis

Decay accelerating factor (DAF) expression at the muscle endplate is an important defence against complement-mediated damage in myasthenia gravis. Previously we implicated the c.-198C > G DAF polymorphism with the development of treatment-resistant myasthenia-associated ophthalmoplegia by showing that the C > G DAF polymorphism prevented lipopolysaccharide-induced upregulation of lymphoblast DAF. We postulated that drugs used in myasthenia gravis may increase the susceptibility of extraocular muscles to complement-mediated damage and studied their effects on endogenous DAF using patient-derived lymphoblasts as well as mouse myotubes. We show that prednisone repressed C > G DAF expression in lymphoblasts and increased their susceptibility to cytotoxicity. Methotrexate, but not azathioprine or cyclosporine, increased DAF in C > G lymphoblasts. In mouse myotubes expressing wild-type Daf, prednisone also repressed Daf expression. Although cyclosporine, azathioprine, and methotrexate increased muscle Daf levels when used alone, upon co-treatment with prednisone only azathioprine maintained myotube Daf levels close to basal. Therefore, prednisone negatively influences DAF expression in C > G lymphoblasts and in myotubes expressing wild-type Daf. We speculate that myasthenic individuals at risk of developing the ophthalmoplegic complication, such as those with C > G DAF, may have inadequate endogenous levels of complement regulatory protein protection in their extraocular muscle in response to prednisone, increasing their susceptibility to complement-mediated damage.