宫颈癌中HPA的表达与细胞增殖、血管生成和转移的关系

目的通过对宫颈癌组织中乙酰肝素酶(heparanase,HPA)、细胞核增殖相关抗原Ki-67和微血管密度的检测,探讨HPA在宫颈癌发生发展中的作用。方法采用免疫组化染色(S-P法)检测67例宫颈癌中HPA、Ki-67和CD34的表达,并与13例正常宫颈组织进行对照研究,分析HPA与患者临床特征、Ki-67和CD34之间的关系。结果67例宫颈癌中49例(73%)阳性表达,而正常13例宫颈组织中无一例阳性表达(P=0.000)。HPA与临床分期、淋巴结转移、细胞增殖和血管生成显著正相关(P值分别为0.001、0.012、0.000、0.000)。结论HPA可能在宫颈癌的发展、浸润、转移和血管生成中起重要作用,并与肿瘤细胞的增殖活性有关,可作为临床预测宫颈癌浸润转移的一个重要参考指标和有价值的治疗靶点。     

Interactions of chronic lead exposure and intermittent stress: consequences for brain catecholamine systems and associated behaviors and HPA axis function.

Elevated lead (Pb) burden and high stress levels are co-occurring risk factors in low socioeconomic status (SES) children. Our previous work demonstrated that maternal Pb exposure can permanently alter hypothalamic-pituitary-adrenal (HPA) axis function and responsivity to stress challenges in offspring. The current study sought to determine the consequences of chronic Pb exposures initiated later in development combined with variable intermittent stress challenges. Male rats were exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions (producing blood Pb levels of <5, 9-15, and 23-27 mug/dl, respectively). Pb itself decreased basal plasma corticosterone, with greater effects at 50 than 150 ppm; 150 ppm reduced both cytosolic and nuclear glucocorticoid receptor binding. Responsivity to stress challenges including novelty, cold, and restraint, was measured as changes in Fixed Interval (FI) schedule-controlled behavior in a subset of rats within each group. FI performance was modified by novelty stress only in Pb-treated rats, whereas cold and restraint stress effects were comparable across groups. Novelty elevated corticosterone equivalently across groups, but cold stress markedly increased corticosterone only in Pb-treated groups. The pattern of Pb-induced changes in serotonin (5-HT) or its metabolite 5-HIAA in frontal cortex, nucleus accumbens, striatum, and hypothalamus resembled that observed for basal corticosterone levels indicating a relationship between these variables. In addition to suggesting the potential for HPA axis-mediated effects of Pb on the central nervous system, these findings also raise questions about whether single chemicals studied in isolation from other relevant risk factors can adequately identify neurotoxic hazards.     

肝郁脾虚证模型大鼠HPA轴中枢相关受体的表达及疏肝健脾方药的干预作用

目的观察肝郁脾虚证模型大鼠下丘脑-垂体-肾上腺皮质激素（HPA）轴中枢相关受体的变化及疏肝健脾方药的干预作用。方法将SD大鼠随机分为正常对照组、肝郁脾虚模型组、疏肝组（柴胡疏肝散组）、健脾组（四君子汤组）、疏肝健脾组（柴疏四君子汤组）,后4组大鼠采用慢性束缚＋饮食失节＋游泳疲劳的方法,连续造模4周,正常组不予处理。于造模第15天,中药各组分别给予柴胡疏肝散4．2g／kg、四君子汤4．53g／kg、柴疏四君汤4．27g／kg灌胃,连续14d。检测大鼠下丘脑促肾上腺皮质激素受体（ACTHR）、糖皮质激素受体（GR）和垂体下丘脑促皮质素释放激素受体（CRHR）、GRmRNA表达水平。结果与正常组相比,模型组大鼠下丘脑ACTHR、GRmRNA及垂体CRHR、GRmRNA表达水平明显降低（P〈0．05,P〈0．01）;与模型组比较,柴疏四君汤组下丘脑ACTHR、GRmRNA及垂体CRHR、GRmRNA表达水平均呈显著性增加（P〈0．05,P〈0．01）,柴胡疏肝散组大鼠下丘脑GR和垂体CRHR、GRmRNA的表达水平均见显著性增加（P〈0．05）,四君子汤组大鼠垂体CRHR、GRmRNA的表达水平显著性增加（P〈0．05）。与四君子汤和柴胡疏肝散比较,柴疏四君汤组大鼠下丘脑ACTHR、GRmRNA的表达水平显著性增加（P〈0．05）,其中柴胡疏肝散组较四君子汤比垂体GRmRNA的表达水平增加更显著（P〈0．05）。结论肝郁脾虚证模型大鼠HPA轴中的中枢相关受体表达呈全面下调,中药三方对模型大鼠下丘脑ACTHR、GRmRNA及垂体CRHR、GRmRNA的表达均有不同程度或选择l生上调作用,其中柴疏四君汤的作用最优,其次是柴胡疏肝散,四君子汤则作用较差。     

泼尼松治疗婴儿痉挛症有效性及HPA轴机制分析

目的 通过研究泼尼松治疗前后婴儿痉挛症(infantile spasm,IS)的发作、脑电图的改变及下丘脑-垂体-肾上腺(hypothalamus-pituitary-adrenal,HPA)轴功能的改变,探讨泼尼松治疗婴儿痉挛症的有效性、HPA轴在IS发病机制中的作用,阐明泼尼松控制痉挛发作的HPA轴相关机制.方法 共收集30例符合标准IS病例(IS组),与30例健康婴幼儿(对照组)对比,对30例IS病例在泼尼松治疗前后进行发作次数记录、EEG监测、HPA轴功能检测,采用化学发光法检测血清皮质醇、促肾上腺皮质激素(adreno-cortico-tropic-hormone,ACTH)水平;利用酶联免疫吸附法检测血清促肾上腺皮质激素释放激素(corticotro-phin Releasing hormone,CRH)水平.结果 用药前IS组血清CRH水平均较正常对照组高,且差异有统计学意义(P<0.05),而IS组血皮质醇、ACTH与正常对照组比较无明显差别,差异无统计学意义(P>0.05);平均每日发作串数、平均每日发作总次数分别与CRH呈正相关(P<0.05);应用泼尼松后,经泼尼松治疗后30例IS病例有19例发作控制,11例发作未控制,有18例脑电高度失律完全缓解,12例脑电高度失律未完全缓解,治疗后每日发作串数及每日发作总次数均较治疗前明显下降,差异有统计学意义(P<0.05),治疗后的DQ较治疗前DQ改善,有统计学意义(P<0.05),病程是泼尼松治疗效果的主要影响因素,病程越长,治疗效果越差,差异有统计学意义(P<0.05).治疗后的CRH、皮质醇、ACTH较治疗前明显下降,差异有统计学意义(P<0.05).结论 泼尼松能有效控制婴儿痉挛症的发作,早期治疗效果更好,IS患儿存在HPA轴功能紊乱,泼尼松能调节HPA轴功能紊乱起到控制痉挛发作的效果.     

电针对慢性应激模型大鼠行为学及HPA轴相关激素的影响

目的 :探讨电针对慢性应激模型大鼠行为学的影响和对下丘脑 垂体 肾上腺轴 (HPA轴 )的调节作用。方法 :采用 7种不同的应激方式交替作用于SD大鼠 2 1d ,制成慢性应激模型 ,用韩氏电针仪 ,以 2Hz频率 ,0 .6mA电流强度 ,电针“百会”和“印堂”穴 ,每天 1次 ,每次 2 0min ,共2 1d。通过开野实验及糖水实验进行大鼠行为学检测 ,运用放射免疫法 (RIA)检测下丘脑CRF、垂体ACTH、肾上腺CORT的含量 ,并与空白组、模型组、百优解组及束缚组做比较。结果 :与空白组相比 ,模型组及模型束缚组开野实验的水平运动次数和垂直运动次数明显减少 ,糖水的摄入量明显减少 ,垂体ACTH、肾上腺CORT的含量明显升高 ,而电针组和百优解组可明显增加开野实验的垂直运动次数及糖水的摄入量 ,并可降低垂体ACTH、肾上腺CORT的分泌。结论 :慢性应激引起大鼠的活动性降低 ,探究行为减少和HPA轴亢进 ,电针可能通过调整垂体ACTH、肾上腺CORT的过度分泌 ,从而纠正HPA轴亢进 ,进而改善慢性应激大鼠的行为学表现。     

Prise en charge des grossesses à risque dans un contexte d’incompatibilité fœto-maternelle plaquettaire et/ou d’allo-immunisation : avis du groupe d’experts du GFHT (Groupe français d’études sur l’hémostase et la thrombose)

IntroductionFetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating disease, seen in 1/800–1000 neonates. FNAIT is the most common cause of early-onset isolated severe neonatal thrombocytopenia in maternity wards. A working group on fetomaternal platelet alloimmunization was created in 2017, under the auspices on the French Group of Thrombosis and Hemostasis (GFHT).ObjectivesThe objective was to survey clinical practices for management of high-risk pregnancies in a context of suspected or confirmed FNAIT.MethodsRecommendations published by the ICTMG were translated in French, and discussed (Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence-based practice, an international approach. British J of Haematology, 2019, 185, 549–562).ResultsThe study involved centers from France, Switzerland and Belgium: Angers, Besançon, Bordeaux, Brest, Créteil/Clamart, Genève, Grenoble, Liège, Lille, Lyon, Marseille, Nantes, Nîmes, Paris (hôpitaux Necker, Robert Debré et Trousseau), Poitiers, Rennes, Saint-Etienne, Strasbourg, Toulouse, Tours.ConclusionsExpert opinion was validated on September 23, 2020 (consensus ≥ 90%).     

Hypothalamic insulin and glucagon-like peptide-1 levels in an animal model of depression and their effect on corticotropin-releasing hormone promoter gene activity in a hypothalamic cell line

Background

In depression, excessive glucocorticoid action may cause maladaptive brain changes, including in the pathways controlling energy metabolism. Insulin and glucagon-like peptide-1 (GLP-1), besides regulation of glucose homeostasis, also possess neurotrophic properties. Current study was aimed at investigating the influence of prenatal stress (PS) on insulin, GLP-1 and their receptor (IR and GLP-1R) levels in the hypothalamus. GLP-1 and GLP-1R were assayed also in the hippocampus and frontal cortex – brain regions mainly affected in depression. The second objective was to determine the influence of exendin-4 and insulin on CRH promoter gene activity in in vitro conditions.

Association between OPCRIT dimensions and polymorphisms of HPA axis genes in bipolar disorder

The aim of the study was to investigate the possible association between polymorphisms of HPA axis genes-CRHR₁ (corticotrophin-releasing hormone receptor), NR3C1 (glucocorticoid receptor) and AVPR1B (arginine vasopressin receptor) and dimensions of bipolar disorder assessed by OPCRIT.     

Ghrelin,Hypothalamus-Pituitary-Adrenal (HPA) Axis and Cushing's Syndrome

Ghrelin, a peptide predominantly produced by the stomach, has been discovered as a natural ligand of the GH Secretagogue receptor type 1a (GHS-R1a), known as specific for synthetic GHS. Ghrelin has recently attracted considerable interest as a new orexigenic factor. However, ghrelin exerts pleiotropic actions that are explained by the widespread distribution of ghrelin and GHS-R expression. Besides strong stimulation of GH secretion, the neuroendocrine ghrelin actions also include significant stimulation of both lactotroph and corticotroph secretion; all these actions depend on acylation of ghrelin in serine-3 that allows binding and activation of the GHS-R1a. However, GHS-R subtypes are likely to exist; they also bind unacylated ghrelin that is, in fact, the most abundant circulating form and exerts some biological actions. Ghrelin secretion is mainly regulated by metabolic signals, namely inhibited by feeding, glucose and insulin while stimulated by energy restriction. The role of glucocorticoids on ghrelin synthesis and secretion is still unclear although morning ghrelin levels have been found reduced in some patients with Cushing's syndrome; this, however, would simply reflect its negative association to body mass. Ghrelin, like synthetic GHS, stimulates ACTH and cortisol secretion in normal subjects and this effect is generally sensitive to the negative glucocorticoid feedback. It is remarkable that, despite hypercortisolism, ghrelin as well as synthetic GHS display marked increase in their stimulatory effect on ACTH and cortisol secretion in patients with Cushing's disease. This is even more intriguing considering that the GH response to ghrelin and GHS is markedly reduced by glucocorticoid excess. It has been demonstrated that the ACTH-releasing effect of ghrelin and GHS is purely mediated at the central level in physiological conditions; its enhancement in the presence of ACTH-secreting tumours is, instead, likely to reflect direct action on GHS receptors present on the neoplastic tissues. In fact, peculiar ACTH hyperresponsiveness to ghrelin and GHS has been observed also in ectopic ACTH-secreting tumours.