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Roberta Giordano Rita Berardelli Ioannis Karamouzis Valentina D’Angelo Andreea Picu Clizia Zichi Beatrice Fussotto Maria Manzo Giulio Mengozzi Ezio Ghigo Emanuela Arvat 《Pituitary》2013,16(3):363-369
The purpose of this study is to verify whether acute pre-treatment with alprazolam (ALP), a benzodiazepine that inhibits HPA secretion in normal subjects, could better characterize patients with subclinical Cushing’s syndrome (SCS) than the 1-mg dexamethasone test (DST). In 22 patients with SCS, 10 with overt Cushing’s syndrome (CS), 11 with non-functioning adrenal incidentalomas (NF) and 14 normal subjects (NS) we studied the effect of ALP (1 mg, p.o. at 2300 hours) on cortisol levels after 1-mg DST. Cortisol levels (mean ± SEM) after DST were lower (P = 0.012) in SCS (3.9 ± 0.3 μg/dl) than in overt CS (10.4 ± 1.9 μg/dl), while they were higher (P = 0.0005) than in NF (1.1 ± 0.1 μg/dl) and NS (1.5 ± 0.1 μg/dl). After ALP pre-treatment, cortisol levels further decreased (P = 0.004) in SCS (3.0 ± 0.3 μg/dl), but neither in CS (9.3 ± 1.3 μg/dl) nor in NF (1.3 ± 0.1 μg/dl) and in NS (1.3 ± 0.1 μg/dl). In SCS, cortisol levels after ALP + 1-mg DST persisted lower (P = 0.0005) than those in CS, but higher (P = 0.0005) than those in NF and NS. Considering individual cases, ALP pre-treatment reduced cortisol levels <3 and <1.8 μg/dl in 50 and 23 % of SCS patients, respectively. ALP amplifies the cortisol inhibition exerted by 1-mg DST in patients with SCS but not in those with CS. The clinical usefulness of ALP to increase the sensitivity of 1-mg DST to identify true autonomous cortisol release in patients with adrenal incidentalomas as well as to predict different clinical outcomes remains to be clarified. 相似文献
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Jochen Oelke Thomas Kaindl Andreea Pasc Zeno Guttenberg Achim Wixforth Motomu Tanaka 《Materials》2013,6(2):669-681
In this paper we demonstrate the combination of supported membranes and so-called flat microfluidics, which enables one to manipulate liquids on flat chip surfaces via “inverse piezoelectric effect”. Here, an alternating external electric field applied to the inter-digital transducers excites a surface acoustic wave on a piezoelectric substrate. Employing lithographic patterning of self-assembled monolayers of alkoxysilanes, we successfully confine a free-standing, hemi-cylindrical channel with the volume of merely 7 µL . The experimentally determined maximum flow velocity scales linearly with the acoustic power, suggesting that our current setup can drive liquids at the speed of up to 7 cm/s (corresponding to a shear rate of 280 s−1) without applying high pressures using a fluidic pump. After the establishment of the functionalization of fluidic chip surfaces with supported membranes, we deposited asymmetric supported membranes displaying well-defined mannose domains and monitored the dynamic adhesion of E. Coli HB101 expressing mannose-binding receptors. Despite of the further technical optimization required for the quantitative analysis, the obtained results demonstrate that the combination of supported membranes and flat fluidics opens a large potential to investigate dynamic adhesion of cells on biofunctional membrane surfaces with the minimum amount of samples, without any fluidic pump. 相似文献
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Lanfranco F Gianotti L Picu A Giordano R Daga GA Mondelli V Malfi G Fassino S Ghigo E Arvat E 《European journal of endocrinology / European Federation of Endocrine Societies》2006,154(5):731-738
OBJECTIVE: Free fatty acids (FFAs) exert a stimulatory effect on the hypothalamic-pituitary-adrenal (HPA) axis in animals and inhibit spontaneous ACTH and cortisol secretion in humans. Patients with anorexia nervosa display concomitant HPA axis hyperactivity and increased lipolysis. We studied the effects of a lipid load on ACTH and cortisol secretion in patients with anorexia nervosa in comparison with normal subjects. DESIGN: Eight women with anorexia nervosa (ANW; means +/- s.e.m.: 23.9 +/- 2.3 years of age; body mass index (BMI): 14.9 +/- 0.6 kg/m2) and seven normal women (NW; 25.6 +/- 2.3 years of age; BMI: 22.8 +/- 1.9 kg/m2) had FFA, ACTH, cortisol, glucose and insulin levels measured in the morning every 30 min for 180 min during i.v. saline or lipid-heparin emulsion (LHE) infusion. RESULTS: During saline infusion, ACTH and cortisol levels decreased spontaneously in both groups, ACTH and cortisol levels in ANW being higher than in NW. LHE infusion led to increased FFA levels in both groups (P < 0.005). The ACTH and cortisol decrease in NW was more marked than during saline infusion (P < 0.05). LHE infusion in ANW was associated with a more pronounced decrease in ACTH levels than during saline infusion (P < 0.05), while cortisol levels were unchanged. At the end of the LHE infusion, a progressive decrease in FFA levels was associated with an increase in ACTH and cortisol concentrations in NW (P < 0.05) but not in ANW in whom FFA levels decreased to a lesser extent (P < 0.05). CONCLUSIONS: This study showed that corticotroph sensitivity to the inhibitory effect of an FFA load is preserved in patients with anorexia nervosa, in spite of persistent adrenal hyperactivity. 相似文献
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Pecori Giraldi F Scaroni C Arvat E Martin M Giordano R Albiger N Leao AA Picu A Mantero F Cavagnini F 《Clinical endocrinology》2006,64(2):219-224
OBJECTIVE: Cushing's disease, hypercortisolism due to a pituitary ACTH-secreting tumour, is a highly morbid illness as yet without effective medical therapy. Recent studies have demonstrated that peroxisome proliferator-activated receptor gamma (PPARgamma) agonists effectively suppress ACTH secretion in a murine tumoral corticotroph cell line, but the few studies conducted so far in patients with ACTH-secreting pituitary adenomas have yielded variable results. DESIGN: Ten patients with Cushing's disease were treated with 4-16 mg rosiglitazone p.o. daily for 1-8 months (median 3 months) and plasma ACTH and cortisol, urinary free cortisol (UFC), as well as parameters of insulin sensitivity, were recorded. An acute challenge with 8 mg rosiglitazone for 2 days preceded long-term rosiglitazone administration. RESULTS: The acute challenge with rosiglitazone did not significantly modify plasma ACTH and cortisol levels. During protracted treatment with rosiglitazone, four patients showed a persistent reduction in UFC levels (up to 24% of pretreatment values), achieving normalization in three. In the others, UFC as well as plasma ACTH and cortisol decrements were inscribed within wide, random oscillations indicating that disease activity was substantially unchanged. Insulin sensitivity was ameliorated in most patients, without relation to ACTH or cortisol secretion. Untoward effects, such as weight gain, oedema and worsening of ecchymoses, were reported in several patients. CONCLUSIONS: Although effective in a subset of patients, protracted rosiglitazone administration did not consistently restrain ACTH and cortisol secretion in patients with Cushing's disease. Further investigations are needed to fully define the therapeutic potential of PPARgamma agonists in this disorder. 相似文献
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Mondelli V Gianotti L Picu A Abbate Daga G Giordano R Berardelli R Pariante CM Fassino S Ghigo E Arvat E 《Psychoneuroendocrinology》2006,31(10):1139-1148
Because of the role of serotonin (5HT) in regulating food intake and mood, several studies have focused their attention on the assessment of serotonergic activity in eating disorders, and in particular in anorexia nervosa, but the results have been inconsistent. Citalopram, a highly selective 5HT reuptake inhibitor, has been recently reported as a neuroendocrine probe to assess the serotonergic function in physiological and pathological conditions. We evaluated the adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL) and growth hormone (GH) secretion during placebo or citalopram IV infusion (20 mg over 120 min), in six women with anorexia nervosa restricter type, and in six healthy women, in order to test the hypothesis that this neurotransmitter system is abnormal in this group of patients. ACTH and PRL secretion was higher during citalopram infusion compared to placebo (p<0.05) in both groups, while cortisol secretion was higher during citalopram infusion only in healthy controls (p<0.05), but not in anorexic patients. GH levels were unaffected by citalopram in both groups. These results demonstrate that serotonergic activation by citalopram affects corticotroph and lactotroph but not somatotroph secretion in anorexic as well as in normal subjects. Our preliminary findings do not support the existence of remarkable alterations in the serotonergic control of anterior pituitary function in anorexia nervosa, while there seems to be an impairment of the adrenal function in this group of patients. 相似文献