米非司酮试验在库欣综合征诊断上的应用

应用一次法口服４ｍｇ／ｋｇ的米非司酮（ＲＵ４８６）观察１７例单纯性肥胖和７例疑似库欣组的病人服药前后的反应，并与１０例正常人以及２９例库欣综合征病人进行比较，发现库欣综合征病人服药以后，血Ｆ２４小时尿Ｆ及血ＡＣＴＨ均无显著性变化（Ｐ〉０．０５），而其他三组各指标均升高（Ｐ〈０．０１）。并得出鉴别库欣综合征与非库欣综合征的标准为：血Ｆ增加的百分比为３０％２４小时尿Ｆ增加百分比为１８％，ＡＣＴＨ增加百     

睫状神经营养因子对应激大鼠体质量的影响及其机制探讨

①目的　探讨睫状神经营养因子 (CNTF)对躯体性和心理性应激大鼠体质量的影响及其与下丘脑促肾上腺皮质素释放激素 (CRH)含量的关系。②方法　建立应激大鼠动物模型 ,应用鼠脑立体定向方法 ,在应激前给予大鼠双侧海马微量注射CNTF ,称量大鼠应激前后的体质量变化 ,并用放射免疫分析法测定大鼠下丘脑CRH含量的变化。③结果　在应激前及应激期间给予双侧海马微量注射CNTF ,可以有效改善应激引起的大鼠体质量的下降 (t=2 .16 3.86 ,P <0 .0 5 ,0 .0 1) ,改善应激引起的下丘脑CRH含量的升高 (t=3.0 5 4.0 3,P <0 .0 1)。④结论　CNTF可以改善应激对大鼠生长的损害 ,其机制可能与CNTF降低应激大鼠下丘脑CRH的含量有关。     

Central noradrenergic lesion impairs the adrenocorticotrophin response to release of endogenous catecholamines

Activation of hypothalamic α(1) -adrenoceptors stimulates the secretion of corticotrophin-releasing factors which in turn stimulate pituitary adrenocorticotrophin (ACTH). This mechanism is important in the physiological control of ACTH secretion. This study assesses the feasibility of using the ACTH response to release of endogenous catecholamines as a means of detecting a hypothalamic noradrenergic lesion in vivo. Intracerebroventricular infusion of the catecholamine neurotoxin, 6-hydroxydopamine, was used to destroy noradrenergic nerve endings in rats, with the purpose of producing a model that could be used to study alterations in ACTH responses that may result from a lesion involving central noradrenergic neurons. 6-Hydroxydopamine (250 μg icv) significantly reduced hypothalamic noradrenaline content, indicating damage to noradrenergic nerve endings, without affecting postsynaptic receptor function, as judged by preservation of the effect of a selective α(1) -adrenergic agonist. Pharmacological release of endogenous catecholamines, effected by combined administration of a catecholamine precursor and an α(2) -adrenergic antagonist, stimulated the secretion of ACTH in control, but not in 6-hydroxydopamine-treated rats. Degeneration of hypothalamic noradrenergic nerve endings is not followed by denervation hypersensitivity, and is therefore accompanied by impairment of the ACTH response to release of endogenous catecholamines.     

Increased transvascular transport of WGA-peroxidase after chronic perinatal stress in the hippocampal microvasculature of the rat

Brain endothelial ultrastructural properties contribute to maintain proper blood-brain barrier (BBB) function. Several physiological and pathological conditions have been shown to alter BBB permeability to blood-borne molecules, acute and chronic stress among them. In the rat, early life stress increased transvascular transport of Evans blue, however, the route of tracer extravasation is not fully known; therefore the aim of the present experiment was to describe the ultrastructural changes in endothelial cells subsequent to chronic perinatal stress in order to ascertain the route for transvascular transport of an electrodense tracer. Pregnant Wistar rats and their litters were used. Four pregnant rats were subjected to forced swimming between gestational days 10 to 20. After delivery, half of the control litters underwent 180 min maternal separation from postnatal day 2 to 20. Controls were kept free of any stress manipulation. At sacrifice between postnatal days 1 to 30 subjects were given intracardially the lectin wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). WGA-HRP stained hippocampi were processed for ultrastructural analysis, transmission electron micrographs were obtained and endothelial ultrastructural parameters quantified using the ImageJ software. Both stress procedures accelerated gross microvessel development by decreasing capillary wall thickness and endothelial microvilli. However, early-life stress also neutralized endothelial glycocalyx, increased vesicle-mediated transport and tended to promote the formation of secondary lysosomes containing endocytosed WGA-HRP vesicles, all parameters of altered endothelial cell function. Tight junction development in both stress groups was similar to the control pups.     

KETANSERIN DOES NOT PREVENT ACTH-INDUCED HYPERTENSION IN SHEEP

The role of serotonin (5HT) in the pathogenesis of ACTH-induced hypertension in sheep has been examined. The pressor responses to injections of 5HT (0.1-30 micrograms/kg) were similar in normotensive and hypertensive sheep. Prior treatment with the 5HT2 receptor antagonist ketanserin had no effect on the development of hypertension produced by ACTH administration.     

HPA axis normalization, estimated by DEX/CRH test, but less alteration on cerebral glucose metabolism in depressed patients receiving ECT after medication treatment failures

OBJECTIVE: To examine the clinical effects of electroconvulsive therapy (ECT) on depressed patients with medication treatment failures, we investigated the alterations in hypothalamic-pituitary-adrenocortical (HPA) function and regional cerebral metabolism rate of glucose (rCMRGlu) after ECT in these patients. METHOD: Before and after ECT, the combined dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test was administered to seven patients who were referred for ECT. In the same patients, (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) was also assessed. RESULTS: Cortisol response in the DEX/CRH test significantly decreased after a successful ECT. A significant hypometabolism in various frontal regions and hypermetabolism in the parietal regions of these patients when compared with controls remained after ECT. CONCLUSION: Depressed patients who failed trials of antidepressant medication showed a remission with ECT that was accompanied by resolution of HPA dysregulation. However, measures of cerebral brain metabolism did not resolve.     

DISSOCIATION BETWEEN CORTICOTROPHIN AND CATECHOLAMINE RESPONSES TO ISOPRENALINE IN HUMANS

1. The pituitary-adrenocortical, sympathoadrenomedullary and renin-angiotensin-aldosterone systems contribute to circulatory and metabolic homeostasis during stress. One possible site of co-ordination of these systems is the beta-adrenoceptor. 2. To determine whether circulating beta-adrenoceptor agonists can act hormonally to stimulate these systems simultaneously, plasma concentrations of corticotrophin (ACTH), noradrenaline, adrenaline and plasma renin activity were measured during graded intravenous infusions of isoprenaline in 20 people. 3. Administration of isoprenaline caused dose-related increases in noradrenaline (94% at the highest dose) and renin activity (189%), but decreases in ACTH (25%) and adrenaline (20%), findings inconsistent with simultaneous activation of these systems by circulating beta-adrenoceptor agonists.