Effects of metyrapone on hypothalamic-pituitary-adrenal axis and sleep in women with post-traumatic stress disorder.

BACKGROUND: Metyrapone blocks cortisol synthesis which results in removal of negative feedback, a stimulation of hypothalamic corticotropin releasing factor (CRF) and a reduction in delta sleep. We previously reported a diminished delta sleep and hypothalamic-pituitary-adrenal (HPA) response to metyrapone in men with post-traumatic stress disorder (PTSD). In this study, we aimed to extend these findings to women. METHODS: Three nights of polysomnography were obtained in 17 women with PTSD and 16 controls. On day 3, metyrapone was administered throughout the day up until bedtime. Plasma adrenocorticotropic hormone (ACTH), cortisol, and 11-deoxycortisol were obtained the morning following sleep recordings the day before and after metyrapone administration. RESULTS: There were no significant between-group differences in hormone concentration and delta sleep at baseline. Relative to controls, women with PTSD had decreased ACTH and delta sleep responses to metyrapone. Decline in delta sleep was associated with the magnitude of increase in ACTH across groups. CONCLUSIONS: Similar to our previous findings in men, the ACTH and sleep electroencephalogram response to metyrapone is attenuated in women with PTSD. These results are consistent with a model of downregulation of CRF receptors in an environment of chronically increased CRF activity or with enhanced negative feedback regulation in PTSD.     

Cortisol moderates the relationship between testosterone and aggression in delinquent male adolescents.

BACKGROUND: In animals, strong evidence exists for an association between testosterone and aggression. In humans, and particularly in children and adolescents, findings have been less consistent. Previous research has suggested that this may partly be due to moderating effects of other factors, e.g., hormones. This study aims to investigate the moderating effect of cortisol on the relationship between testosterone and subtypes of aggression in delinquent male adolescents. METHODS: Participants were 103 boys (mean age 13.7) referred to a delinquency diversion program. Testosterone and cortisol levels were determined from saliva samples collected during resting conditions and related to self-report scores on overt and covert aggression. RESULTS: Linear regression analyses revealed a significant interaction between cortisol and testosterone in relation to overt aggression, with a significant positive relationship between testosterone and overt aggression in subjects with low cortisol levels but not in subjects with high cortisol levels. Using the same model for covert aggression, no significant effects of testosterone, cortisol, or testosterone x cortisol interaction were found. CONCLUSIONS: These results indicate a moderating effect of cortisol on the relationship between testosterone and overt aggression in delinquent male adolescents. Implications and directions for future research are discussed.     

涎腺腺样囊性癌氩离子激光流式细胞术分析及其临床意义

为探讨流式细胞术对涎腺腺样囊性癌的诊断和预后估计的价值，对４１例腺样囊性癌行流式细胞术分析。结果，平均ＤＮＡ指数为１．１７９，Ｓ期细胞比例为２９．４９％，细胞增殖指数为４２．６７％，均明显高于正常组织。异倍体检出率为７０．７３％。随着肿瘤的增大和恶性程度的增加，其异倍体率、ＤＮＡ指数和Ｓ期细胞比例值也相应增加。流式细胞术为涎腺腺样囊性癌的病理诊断和确定恶性程度提供了有效的辅助诊断措施，但尚不能判断预后。     

Chronic Alcohol Ingestion Enhances Tumor Necrosis Factor-α Expression and Salivary Gland Apoptosis

We investigated the extent of induction in sublingual salivary gland cells apoptosis and tumor necrosis factor-α (TNF-α) expression with chronic ethanol ingestion. The experiments were conducted on rats pair-fed for 8 weeks with alcohol-containing and control liquid diet. The animals were killed, their sublingual glands dissected, and the glandular tissue used for quantitization of TNF-α expression and the assays of acinar cells apoptosis employing sandwich enzyme immunoassay for histone-associated DNA fragments. The mean value for TNF-α in sublingual gland of the control group was 22.3 pg/mg of protein and showed a 1.6-fold increase in the chronic ethanol diet group to 36.5 pg/mg of protein. In comparison with the controls, the sublingual gland of the chronic ethanol diet group also exhibited a 3.4-fold enhancement in acinar cell apoptosis. These findings suggest that chronic ethanol ingestion causes the enhancement in TNF-α expression and leads to the induction in salivary gland acinar cells apoptosis. Thus, the diminished secretion of saliva in alcoholics may be a direct result of increased salivary gland apoptosis.     

Modeling the pharmacokinetics and pharmacodynamics of dexamethasone in depressed patients

Summary Changes in time course effected by cortisol suppression and the relationship of these changes to the plasma dexamethasone concentration of suppressor and non-suppressor patients are described in this report on a combined pharmacokinetic-pharmacodynamic model.Thirteen depressed patients (8 suppressors and 5 non-suppressors) received an intravenous dose (1.5 mg) of dexamethasone. The drug-induced effect changes are found to lag behind, in time, the plasma drug level changes. To accurately relate the temporal relationship of effect changes to plasma dexamethasone levels, a pharmacodynamic model (sigmoid-Emax) was combined with a pharmacokinetic model that incorporated an effect compartment. The magnitude of the time-lag was quantified by the half-time of equilibration between concentrations in the hypothetical effect compartment and the plasma dexamethasone levels (t_&frac;k_eo).The t_&frac;k_eo of the nonsuppressing group was about 50 of that of the suppressing group, indicating that for a given plasma level the onset and termination of effect for the nonsuppressing group is about two times more rapid than for the suppressing group. Moreover, the model can estimate the effect-site concentration that causes one-half of the maximal predicted effect (EC₅₀), a measure of an individual's sensitivity to dexamethasone. The receptor sensitivity (as determined from the EC₅₀ ratio) of the suppressing group was about twice that of the nonsuppressing group.     

高效液相梯度洗脱法测定血清中氢化可的松和可的松的含量

目的　测定血清中氢化可的松和可的松的比值以反映人体肝脏 1 1 β -羟类固醇脱氢酶的活性 ,为其研究提供一个有效的分析手段。方法　HPLC -UV法 ,梯度洗脱 ,内标定量。结果　血清中氢化可的松在 50～ 2 0 0μg·L-1 、可的松在 1 0～ 50 μg·L-1 范围内其线性回归方程分别为Y =- 0 .42 5 +0 .0 1 0X、Y =- 0 .1 63 +0 .0 50X ,相对回收率分别为 (1 0 2 .5± 3 .6) %、(97.6± 6 .0 ) %。 82名健康志愿者血中氢化可的松和可的松的浓度分别为 (1 32 .2± 44 .5) μg·L-1 和 (1 9.7± 5 .0 ) μg·L-1 ,其比值为 6 .89± 2 .2 6。结论　本法操作简便、灵敏可靠 ,符合人体血样糖皮质激素测定的要求     

The effects of aging on the circadian rhythm of serum cortisol in the dog

The purpose of this study was to determine if aging affects the circadian rhythm of serum cortisol. Female beagle dogs belonging to three age groups were used: adult (3.3 ± 0.6 (SD) years), old (12.1 ± 0.3 years), and puppies (8.4 ± 0.2 weeks). Blood samples were collected by cephalic or jugular venipuncture at 3-h intervals during three 24-h periods and analyzed for total serum cortisol concentrations by radioimmunoassay. The circadian rhythm was present in the serum cortisol of adult animals, but no significant changes during a 24-h period could be detected in the old animals. No circadian rhythm in serum cortisol was present in the puppies. It is concluded that the circadian rhythm in plasma cortisol is disrupted in old animals and is not yet developed in puppies.     

20例涎腺多形性腺瘤的免疫组织化学观察

采用5种与分化有关的抗体:EMA、CEA、Lys、Actvn、S-100对20例涎腺多形性腺瘤进行免疫组织化学技术观察,结果显示:以上5种抗体均可作为多形性腺瘤诊断检测全面反映的分化表型。     

Antiserotonergic inhibition of calcitonin-induced increase of β-endorphin,ACTH, and cortisol secretion

Summary In a previous study we observed that calcitonin increases -endorphin, ACTH, and cortisol secretion. We assumed that calcitonin might have a modulatory role on the pituitary function. The present study was initiated to clarify whether this effect is due to a direct pituitary stimulation or to an indirect stimulation through CRF (corticotropin releasing factor).Fourteen healthy subjects, aged 30–60 years were investigated. All the subjects received 100IU Salmon calcitonin Sandoz i.v. at 8a.m. (time 0). Plasma -endorphin, ACTH and cortisol were estimated every 30min from – 30 to 120 min by specific radioimmunoassay. The same parameters were estimated a second time, at the same intervals, when cyproheptadine 8 mg (7 subjects) and 40 mg propranolol (7 subjects) were given per os at – 30 min and calcitonin i.v. at time 0. -endorphin, ACTH and cortisol levels (Mean ±SEM) rose significantly after calcitonin (peak value at 30–90 min) from 5.2 ±0.7 to 15.1±2.6 pmol/l; from 43.0±2.7 to 70.7±4.1 pg/ml and from 10.6±1.5 to 19.6 ±2.1 g/100 ml respectively (p< 0.0001 by analysis of variance and covariance and repeated measures). Propranolol 40 mg (per os) administered at time – 30 did not alter the response of -endorphin, ACTH and cortisol to calcitonin (infused at time 0).Cyproheptadine, the antiserotonergic substance that inhibits the synthesis and release of CRF completely inhibited the stimulatory effect of calcitonin.We conclude that probably calcitonin has a modulatory role on the hypothalamo-pituitary adrenal axis and that it acts at the hypothalamic level probably by stimulating CRF secretion.