Oxidative stress and HNE conjugation of GLUT3 are increased in the hippocampus of diabetic rats subjected to stress

Recent studies demonstrate that cellular, molecular and morphological changes induced by stress in rats are accelerated when there is a pre-existing strain upon their already compromised adaptive responses to internal or external stimuli, such as may occur with uncontrolled diabetes mellitus. The deleterious actions of diabetes and stress may increase oxidative stress in the brain, leading to increases in neuronal vulnerability. In an attempt to determine if stress, diabetes or stress+diabetes increases oxidative stress in the hippocampus, radioimmunocytochemistry was performed using polyclonal antisera that recognize proteins conjugated by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE). Radioimmunocytochemistry revealed that HNE protein conjugation is increased in all subregions of the hippocampus of streptozotocin (STZ) diabetic rats, rats subjected to restraint stress and STZ diabetic rats subjected to stress. Such increases were not significant in the cortex. Because increases in oxidative stress may contribute to stress- and diabetes-mediated decreases in hippocampal neuronal glucose utilization, we examined the stress/diabetes mediated HNE protein conjugation of the neuron specific glucose transporter, GLUT3. GLUT3 immunoprecipitated from hippocampal membranes of diabetic rats subjected to stress exhibited significant increases in HNE immunolabeling compared to control rats, suggesting that HNE protein conjugation of GLUT3 contributes to decreases in neuronal glucose utilization observed during diabetes and exposure to stress. Collectively, these results demonstrate that the hippocampus is vulnerable to increases in oxidative stress produced by diabetes and stress. In addition, increases in HNE protein conjugation of GLUT3 provide a potential mechanism for stress- and diabetes-mediated decreases in hippocampal neuronal glucose utilization.     

Brainstem catecholaminergic neurons activated by hypoxemia express GR and are coordinately activated with fetal sheep hypothalamic paraventricular CRH neurons

In late gestation, challenges to fetal homeostasis are accompanied by increases in adrenocorticotropin (ACTH) concentrations in fetal peripheral plasma and Fos (c-fos protein) activation in corticotropin-releasing hormone (CRH) neurons of the fetal hypothalamic paraventricular nucleus (PVN). In adults, ventrolateral brainstem catecholaminergic (CA) neurons (A1/C1, A2/C2) project to the parvocellular neurons of the PVN, possess glucocorticoid receptors (GR) and are Fos activated in parallel with CRH neurons of the PVN during hypoxia. Such observations suggest a role for the aforementioned medullary neurons in the function of the hypothalamo-pituitary-adrenal axis. The present study utilized late gestation fetal sheep, stereotaxic methodology and retrograde axon tracing and immunocytochemical techniques to investigate the relationship between activation of fetal brainstem CA neurons and activation of fetal PVN CRH immunopositive neurons in response to hypoxemia. Results indicated that: (1) the largest brainstem CA projection to PVN CRH neurons is from A1/C1 neurons, (2) brainstem neurons exhibit GR immunostaining and (3) brainstem CA neurons show a strong correlation (A1/C1 - r(2)=0.894, P<0.005; A2/C2 - r(2)=0. 848; P<0.002) of Fos activation with Fos activation in PVN CRH cells. We conclude that in late gestation the brainstem A1/C1 and A2/C2 areas are in position to influence the function of the hypothalamo-pituitary-adrenal axis during hypoxemic challenges to homeostasis in a fashion similar to that which has been demonstrated in the adult rat.     

Regulation of glucocorticoid receptor mRNA and heat shock protein 70 mRNA in the developing sheep brain

Fetal hypothalamo-pituitary-adrenal (HPA) activity increases dramatically at term in sheep, however, little is known about the regulation of glucocorticoid feedback in the developing brain. Heat shock protein 70 (hsp70) is closely associated with glucocorticoid actions within the cell. We hypothesized that there is a decrease in glucocorticoid negative feedback in the brain, near term, resulting from changes in the expression of glucocorticoid receptors (GR) and hsp70. Brains were removed at various stages of development. GR mRNA levels in the paraventricular nucleus (PVN) and cortex, and hsp70 mRNA in the PVN were determined by in situ hybridization. In the hippocampus, GR mRNA levels were measured by Northern analysis. In the PVN, GR mRNA was present by d60. GR mRNA levels reached a peak at d100-110, but then decreased significantly with progression of gestation, and were lowest at term. Hippocampal GR mRNA levels were highest on day 130 of gestation, decreasing to low levels at term. In the cerebral cortex, GR mRNA levels were expressed at high levels in all layers of the cortex by day 110 of gestation with levels decreasing to term. Hsp70 mRNA was present in both parvocellular and magnocellular regions of the PVN, and there was no significant change in late gestation. In conclusion, (1) The high levels of GR mRNA present in the PVN, hippocampus and cerebral cortex during fetal life are likely important in development of these structures at a time when circulating glucocorticoids are low. (2) Changes in GR mRNA levels in the PVN are not associated with alterations in the expression of hsp70. (3) The decrease in GR mRNA in the hippocampus and PVN in late gestation, at a time when fetal plasma cortisol is increasing, likely facilitates maintained hypothalamic drive to the pituitary corticotroph.     

多疗程糖皮质激素治疗孕34周前早产临床分析

目的:评价多疗程糖皮质激素(GC)治疗孕34周前早产的作用。方法:回顾性分析华西第二医院收治的150例孕34周前早产分娩的临床资料,根据糖皮质激素治疗情况分为未治疗组(对照组)、不足1疗程组、1疗程组、2疗程组和3疗程组。结果:GC治疗组与对照组的新生儿出生体重和身长Z积分值差异无显著性(P>0.05);Logistic回归分析显示2疗程GC治疗可以减少新生儿5分钟窒息发生,但重复疗程GC治疗对新生儿RDS、脑室内出血、吸入性肺炎和婴幼儿死亡、远期并发症等无保护性作用。结论:孕34周前糖皮质激素治疗早产是有好处的,但重复疗程治疗的作用尚需进一步观察。     

大剂量糖皮质激素联合抗蛇毒血清治疗竹叶青蛇伤致DIC的疗效

目的观察大剂量糖皮质激素联合抗蛇毒血清在治疗竹叶青蛇伤致DIC中的疗效。方法57例竹叶青蛇伤致DIC患者按单盲随机法分为两组,对照组28例,治疗组29例。对照组予常规综合治疗+抗蝮蛇血清;治疗组在对照组基础上加用甲基强的松龙1000m g/d,观察两组疗效及凝血酶原时间(PT)、纤维蛋白原(Fg)和血小板(PLT)的恢复时间。结果治疗组总有效率96.6%,对照组总有效率75.0%,两者差异有显著性(P<0.05);治疗组PT、Fg、PLT与对照组比较,有显著性差异(P<0.05)。结论大剂量糖皮质激素联合抗蛇毒血清治疗竹叶青蛇伤致DIC可明显缩短凝血指标恢复时间及提高疗效。可以对竹叶青蛇毒起较好的中和作用,取得满意的临床治疗效果。     

上胸段硬膜外阻滞对脑血管痉挛兔脑组织GR表达及血清炎性细胞因子含量的影响

目的探讨上胸段硬膜外阻滞(HTEB)对蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)兔的基底动脉周围脑组织糖皮质激素受体(GR)mRNA的表达及血清炎性细胞因子含量的影响。方法采用枕大池二次注血法制备兔SAH模型,将45只硬膜外阻滞成功的动物按随机数字表法随机分成3组(n=15):对照组、假手术组和HTEB组;然后各组再分为注血后l、7、14 d三个亚组(n=5)。用经颅多普勒超声检测注射前和注射后1、7、14 d动物基底动脉平均血流速度(Vm)。测量并比较各组基底动脉周围脑组织GR mRNA表达水平及血清炎性细胞因子[肿瘤坏死因子-α(TNF-α)及白细胞介素(IL)-1、6]含量的差异。结果对照组基底动脉Vm、血清中TNF-α、IL-1和IL-6含量最高,HTEB组次之,假手术组最低,三组之间均差异显著(P<0.05)。脑组织中GR表达水平假手术组最高,HTEB组次之,对照组最低,三组之间差异显著(P<0.05)。结论HTEB可增加SAH后CVS的兔基底动脉周围脑组织GR的表达,并抑制TNF-α、IL-1、IL-6过度分泌,从而减轻CVS。     

Quantitative analysis of skeletal muscle mass in patients with rheumatic diseases under glucocorticoid therapy – Comparison among bioelectrical impedance analysis,computed tomography,and magnetic resonance imaging

Abstract

Objectives. To determine the availability of bioelectrical impedance analysis (BIA), computed tomography (CT), and magnetic resonance imaging (MRI) for measurement of skeletal muscle mass in patients with rheumatic diseases and quantitatively assess skeletal muscle loss after glucocorticoid (GC) treatment.

Methods. The data from 22 patients with rheumatic diseases were retrospectively obtained. The muscle mass of body segments was measured with a BIA device in terms of skeletal muscle mass index (SMI). Cross-sectional area (CSA) was obtained from CT and MRI scans at the mid-thigh level using the image analysis program. We further assessed the data of three different measurements before and after GC treatment in 7 patients with rheumatic diseases.

Results. SMI of whole body was significantly correlated with estimated muscle volume and mid-thigh muscle CSA with CT and MRI (p < 0.01). Significant correlations between SMI and mid-thigh muscle CSA of each leg were also found (p < 0.01). All the three measurements were negatively correlated with GC dosage (p < 0.01). Significant decline in mid-thigh muscle CSA with CT and MRI was found after GC treatment in 7 patients (p < 0.02). Those patients showed significant decline in SMI of whole body after GC treatment, but not in SMI of each leg. On the other hand, significant correlations between mid-thigh muscle CSA with CT and MRI were found before and after GC treatment (p < 0.01).

Conclusions. GC-related skeletal muscle loss could be quantitatively assessed with BIA, CT, or MRI in patients with rheumatic diseases, and CT and MRI appeared to be more accurate than BIA.     

NB-UVB及羟氯喹和糖皮质激素三联疗法治疗泛发性扁平苔藓1例

患者男,57岁。口腔溃烂、手足及躯干起疹1月余。背部皮损组织病理可见胶样小体,诊断:泛发性扁平苔藓。予NB-UVB联合糖皮质激素口服及羟氯喹治疗,8周后皮疹消退。     

糖皮质激素在毛细支气管炎治疗中的应用

目的探讨糖皮质激素的不同给药方式对婴幼儿毛细支气管炎治疗效果的影响。方法 89例毛细支气管炎患儿随机分成三组：实验Ⅰ组、实验Ⅱ组、实验Ⅲ组。三组实验对象在常规抗病毒、化痰及对症治疗的基础上,实验Ⅰ组给予甲泼尼龙琥珀酸钠静脉滴注;实验Ⅱ组给予丙酸氟替卡松定量气雾剂储雾罐辅助吸入;实验Ⅲ组给予布地奈德混悬液雾化吸入。对三组治疗疗效、主要症状及体征缓解和消失时间、治疗5 d后临床评分进行比较分析。结果 1三组患儿在主要症状缓解时间方面,除肺部湿啰音消失时间及住院天数实验Ⅱ组与Ⅲ组类似外（P〉0.05）,余症状实验Ⅲ组均短于Ⅰ、Ⅱ组（P〈0.05）。2治疗效果Ⅲ、Ⅱ组均优于Ⅰ组（P〈0.05）。3三组治疗后临床症状评分较治疗前评分均有所降低（P〈0.05）,Ⅲ组降低明显（P〈0.05）。结论局部吸入糖皮质激素较全身用糖皮质激素在毛细支气管炎治疗过程中起效快,能有效缩短病程,不良反应小,更能提高治愈率。其中布地奈德混悬液氧气驱动雾化吸入更能缓解喘憋,缩短喘息及咳嗽持续时间,患儿易接受,易于推广。