The effect of growth hormone replacement on cortisol metabolism and glucocorticoid sensitivity in hypopituitary adults

OBJECTIVE: Growth hormone (GH) replacement therapy in hypopituitary adults is associated with sodium and water retention. The underlying mechanisms are incompletely understood and a possible contribution of altered cortisol metabolism or action has not been evaluated. We have investigated the effect of GH replacement therapy on cortisol metabolism, cortisol binding globulin and in-vitro glucocorticoid sensitivity in a group of adult hypopituitary patients. DESIGN AND PATIENTS: We studied 19 adult hypopituitary patients (18 adult onset, M:F, 6:13), who were receiving conventional hydrocortisone (16 patients), thyroxine (14 patients), triiodothyronine (1 patient), sex steroid (9 patients), human chorionic gonadotrophin (1 patient) or desmopressin (6 patients) replacement during a 6-month, double blind controlled trial of GH therapy (active:placebo, 8:11) followed by a 6-month open phase of GH (mean dose: 0.2 IU/kg/week, range 0.051-0.27) and after a 6-week washout phase following discontinuation of GH therapy. MEASUREMENTS: Twenty-four-hour urine free cortisol, cortisol metabolites (CoM), ratio 11-hydroxy/11-oxo CoM (F/E) and ratio 5 alpha/beta tetrahydrocortisol were measured at 6 months, 12 months and after the 6 week washout phase. Serum cortisol binding globulin was measured basally, at 6 months, 12 months and after washout. Glucocorticoid sensitivity was determined in lymphocyte preparations from 8 patients, during GH therapy and after washout, using an in-vitro technique dependent on dexamethasone suppression of phytohaemagglutinin-stimulated thymidine incorporation into DNA. Plasma renin activity and aldosterone were measured after 6-12 months GH therapy and after washout. RESULTS: After 6 months of GH, in patients on hydrocortisone (n = 9), there were significant decreases in CoM (mean decrement 21%, P < 0.01), F/E (mean decreased from 1.27 to 1.0, P = 0.04; reference range 0.33-1.29) and 5 alpha/5 beta tetrahydrocortisol (mean decreased from 0.67 to 0.48, P = 0.01) and a subsequent increase after washout. Patients not on hydrocortisone (n = 2) demonstrated a normal basal F/E falling by 25% on GH therapy but no change in CoM. During 12 months of GH therapy, patients on hydrocortisone (n = 7) demonstrated a further trend to decrement in CoM (P = 0.09) which reversed after washout (P = 0.04). Urine free cortisol tended to fall during GH therapy and increased significantly following washout after 12 months treatment (P < 0.02). Serum cortisol binding globulin decreased by 20% (P < 0.05) during 12 months GH treatment but remained within the reference range. In-vitro studies demonstrated a trend to reduced glucocorticoid sensitivity on GH therapy; the maximum inhibition of phytohaemagglutinin by dexamethasone tended to be less on GH therapy (P = 0.052) and was also lower than in 29 normal volunteers (P < 0.05). There were no significant changes in plasma renin but there was a small increment in aldosterone in recumbent patients (P = 0.04) during the open phase of GH therapy in the placebo arm. CONCLUSIONS: GH therapy in hypopituitary adults is associated with an apparent reduction in availability of administered hydrocortisone as measured by urine cortisol metabolites and urine free cortisol. This effect is unlikely to be clinically significant except possibly in ACTH deficient subjects on suboptimal hydrocortisone replacement. The changes in F/E suggest that GH may directly or indirectly modulate the activity of 11 beta-hydroxysteroid dehydrogenase. The apparent decrease in glucocorticoid sensitivity during GH therapy, demonstrated in vitro, merits further investigation.     

AutoCAD在更改连铸设备布局设计中的应用

将AutoCAD应用到更改连铸设备布局设计中，可使更改过程一目了然。     

N- and O-glycosylation muteins of recombinant human erythropoietin secreted from BHK-21 cells

Single-site glycomuteins of recombinant human erythropoietin (rhuEpo) were constructed and transiently and stably expressed in BHK-21 cells. The transient expression levels varied among muteins, being highest for mutein rhuEpoGln24 followed by wild-type rhuEpo (rhuEpowt). All other glycomuteins, including rhuEpoGln38, rhuEpoGln83, rhuEpoThr126, and rhuEpoGly126, were secreted at lower levels than rhuEpowt. Muteins expressed in stable cell lines showed similar differences in expression levels. Also each mutein could be affinity-purified from culture supernatants, and was biologically active in vivo. Based on secretion rates from BHK-21 cells, the most potent erythropoietin was rhuEpoGln24. This mutein is also considered to have biologic activities that are superior to rhuEpowt.     

航空反潜综合模拟训练系统研究与设计

主要介绍分布式交互仿真技术在航空反潜模拟训练系统设计上的应用,阐述了模拟系统的组成,根据系统的设计要求,构造了分布式仿真对象,并对每个对象构建了仿真模块,最后分析了航空反潜综合训练系统的设计思想。     

使用Python开发跨平台的单词助记程序

介绍使用Python语言开发跨平台的单词助记程序原型的方法,包括安装配置Python环境、单词数据词典文件的格式、程序的主要代码和运行过程。     

大时延遥操作系统的波变量双边自适应控制

针对通信时延对遥操作系统稳定性和透明性的影响,研究了一种基于双边自适应控制和波变量理论的控制方法。通过设计波控制器保证通信传输模块的无源性,在保证系统稳定的基础上,调节波阻抗系数来提高系统的透明性,并在时延10 s的情况下进行主从端速度、位置和力的跟踪仿真实验,结果表明该方法和已有的双边自适应方法相比既能保证系统稳定且透明性好,达到较好的控制效果。     

Corrosion inhibition in magnesium-aluminium-based alloys induced by rapid solidification processing

The effect of rapid solidification on the corrosion behaviour in aerated 0.001 M NaCl solution of Mg-Al alloys containing 9.6 to 23.4wt% AI has been investigated in comparison with chill-cast material. Polarization studies show that rapid solidification decreases corrosion current by up to two orders of magnitude corresponding to a corrosion rate of 6 to 11 mil y^–1. Increasing the aluminium content in solid solution by rapid solidification gave rise to a steep increase in pitting potential between 10 and 23 wt% Al and resulted in development of an anodic plateau at 30Acm^–2 attributable to magnesium depletion for the alloy surface and formation of a protective film. Chemical analysis of the electrolyte as a function of dissolution time for the rapidly solidified material indicated that initially only magnesium dissolved and that this dissolution of magnesium ceased within 2 to 5 min. The results indicate the formation of an aluminium-enriched interdiffusion zone at the surface underlying a more stable surface oxide than for ingot-processed Mg-Al-based alloys.     

Viscous flow behaviour of NixZr100−x metallic glasses from Ni30Zr70 to Ni64Zr36

The compositional dependence of viscous flow in the Ni _x Zr_100–x amorphous system was investigated under non-isothermal conditions at a heating rate of 10 K min^–1in the compositional range fromx=30 tox=64 at % with the aid of a Hereaus TMA 500 dilatometer. The crystallization behaviour of the same glassy alloys under the same non-isothermal conditions was studied with a Perkin-Elmer DSC 7 differential scanning calorimeter. The characteristic crystallization and viscous flow parameters (the onset temperature,T _x, of crystallization; the temperature,T _m, of maximum heat evolution of the first crystallization step; the enthalpy, H _x, of crystallization; the activation energy,Q _x, of crystallization; the glass transition temperature,T _g; the viscosity values (T _g) and _min; and the activation energy for viscous flowQ (T>T _g), were shown to be dependent on composition. This dependence was examined on the basis of the equilibrium phase diagram of the Ni-Zr-system, and it is shown that glassy alloys possessing eutectic compositions manifest the greatest thermal stability because of the long-range atomic diffusion needed for crystallization to occur. Glassy alloys with nearly peritectoid compositions show low thermal stability, as no long-range diffusion is needed for the formation of the stable crystallization end-products NiZr₂ and NiZr. In all cases, the crystallization process is governed by viscosity flow of these glassy alloys.