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Biomedical subjects

F Orio

Publications and source records attributed to F Orio.

At least 19 recordsLinked to original sources

Growth hormone status in morbidly obese subjects and correlation with body composition.

Morbidly obese subjects are characterized by multiple endocrine abnormalities and these are paralleled by unfavorable changes in body composition. In obese individuals, either 24-h spontaneous or stimulated GH secretion is impaired without an organic pituitary disease and the severity of the secretory defect is proportional to the degree of obesity. The GHRH+arginine (GHRH+ARG) test is likely to be the overall test of choice in clinical practice to differentiate GH deficiency (GHD) patients. Similarly to other provocative tests, GHRH+ARG is influenced by obesity per se. Therefore, a new cut-off limit of peak GH response of 4.2 microg/l in obese subjects has been recently assumed. The aim of the present study was to investigate the reciprocal influence between decreased GH secretion and body composition in a group of 110 morbidly obese subjects, using the new cut-off limit of peak GH response to GHRH+ARG test for these subjects. In our study, GHD was identified in 27.3% of the obese subjects, without gender difference. In GDH obese subjects body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), fat mass (FM), and resistance (R) were higher while reactance (Xc), phase angle, body cell mass (BCM), IGF-I, or IGF-I z-scores were lower than in normal responders (p<0.001). In all obese subjects, GH peak levels showed a negative correlation with age, BMI, waist circumference and FM, and a positive correlation with IGF-I. In the stepwise multiple linear regression, waist circumference and FM were the major determinants of GH peak levels and IGF-I. In conclusion, using the new cut-off limit of peak GH response to GHRH+ARG test for obese subjects, about 1/3 morbidly obese subjects were GHD. GHD subjects showed a significantly different body composition compared with normal responders, and the secretory defect was correlated to different anthropometric variables with waist circumference and FM as the major determinants.

Adipose Tissue↗

Endothelial dysfunction in PCOS: role of obesity and adipose hormones.

PURPOSE: Polycystic ovary syndrome (PCOS) is an extremely prevalent disorder in which elevated blood markers of cardiovascular risk and altered endothelial function have been found. This study was designed to determine if abnormal carotid intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) in young women with PCOS may be explained by insulin resistance and elevated adipocytokines. METHODS: A prospective study in 50 young women with PCOS (age: 25.2 +/- 1 years; body mass index [BMI]: 28.7 +/- 0.8) and 50 matched ovulatory controls (age: 25.1 +/- 0.7 years; BMI: 28.5 +/- 0.5) was performed. Carotid IMT, brachial FMD, and blood for fasting glucose, insulin, leptin, adiponectin and resistin were measured. RESULTS: PCOS, IMT was increased (P <.01), FMD was decreased (P <.01), fasting insulin was increased (P <.01), QUICKI (a marker of insulin resistance) was decreased (P <.01), and adiponectin was lower (P <.05), whereas leptin and resistin were not different compared with matched controls. Whereas BMI or waist/hip ratios did not correlate with IMT or FMD, insulin and QUICKI correlated positively and negatively with IMT (P <.01). There was a significant negative correlation between adiponectin and IMT (P <.05). These correlations were unchanged when adjusting for BMI and the correlation between IMT and adiponectin was unaffected by insulin resistance parameters. CONCLUSIONS: These data suggest that young women with PCOS have evidence for altered endothelial function. Adverse endothelial parameters were correlated with insulin resistance and lower adiponectin. Both insulin resistance and adiponectin appear to be important parameters. It is hypothesized that the type of fat distribution may influence these factors.

Adipocytes↗

Effects of various antireabsorptive treatments on bone mineral density in hypogonadal young women after allogeneic stem cell transplantation.

Ovarian failure after allogeneic stem cell transplant (allo-SCT) is an important risk factor for development of osteoporosis. We investigated the effects of various antiresorptive treatments in long-term surviving females with ovarian failure after allo-SCT. A total of 60 women with osteoporosis or osteopenia were divided randomly into four groups of 15 women each. Group 1 was treated with calcium and vitamin D alone, group 2 received the same treatment in combination with hormone replacement therapy (HRT), group 3 received risedronate (35 mg weekly, orally for 1 year) and group 4 zoledronic acid (3 monthly doses of 4 mg (intravenous)). All groups were similar for age, body mass index, underlying disease and time elapsed from transplant. Lumbar and femoral bone mineral density (BMD) were measured at baseline and after 12 months, together with serum osteocalcin and urinary hydroxyproline. At 12 months, a significant decrease in lumbar and femoral BMD was observed in group 1 and a milder decrease in group 2. Risedronate treatment increased significantly lumbar BMD and prevented bone loss at the femoral neck. Zoledronic acid increased significantly both lumbar and femoral BMD. In groups 3 and 4 the hydroxyproline excretion was significantly reduced, while osteocalcin mildly increased only in group 4. In conclusion, bisphosphonate administration is useful to prevent and treat bone demineralization in young adult women after allo-SCT.

Adolescent↗

Effects of neridronate treatment in elderly women with osteoporosis.

Osteoporosis is a common disorder, especially among elderly post-menopausal women. Elderly women are often affected by co-morbidities, impaired gastrointestinal function and reduced mobility; therefore, the treatment strategy for their osteoporosis can be difficult. In this randomized pilot study, we have investigated the effects of a 12-month treatment with neridronate on bone mineral density (BMD), bone turnover markers and quality of life (QoL). The study included 40 women (age, 65-80 yr; post-menopausal period, >15yr) from a single osteoporosis centre. Twenty women received a monthly im injection of 25 mg of neridronate associated with a daily dose of 500 mg of calcium and 400 U of vitamin D. Twenty women received calcium plus vitamin D supplements alone. Changes in BMD at the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. Serum type I collagen C-telopeptide (sCTX), urinary free-deoxypyridinoline (ufDPD), bone alkaline phosphatase (ALP) and serum osteocalcin levels were determined. For the QoL assessment, the Italian version of the SF-36 test was administrated. Spine and hip BMD rose by 6.6 +/- 3 and 4.2 +/- 2.3%, respectively (p < 0.05), after 12 months of neridronate treatment. Markers of skeletal turnover significantly fell already after 3 months of neridronate treatment and decreased progressively thereafter within 12 months. The mean decrease at 12 months ranged from 38 +/- 11% for sCTX to 25.2 +/- 15% for ufDPD (p < 0.001, all). The mean improvement in QoL in the treated group was 45.7% for bodily pain, 37.5% for general health perception, 23.1% for vitality, 18% for emotional role functioning and 12% for physical role functioning. The changes observed in BMD, turnover markers and QoL in the untreated group were ns. The intermittent neridronate administration was easily manageable and well tolerated. In conclusion, neridronate currently represents a valid option for the treatment of osteoporosis, since it helps just as much as oral BPs in the improvement of BMD and in particular conditions it can be even more effective.

Absorptiometry, Photon↗

Role of dehydroepiandrosterone sulfate levels on body composition after laparoscopic adjustable gastric banding in pre-menopausal morbidly obese women.

UNLABELLED: In humans, dehydroepiandrosterone (DHEAS) has been postulated to have anabolic and lipolytic properties that could potentially counteract the catabolic effect of cortisol. DHEAS secretion is reduced in morbid obesity, likely due to hyperinsulinemia, and laparoscopic adjustable gastric banding (LASGB), by inducing considerable and rapid weight loss, reduces insulin levels. To investigate the role of decreased insulin levels after LASGB-induced weight loss on DHEAS levels and on body composition changes, we studied 30 pre-menopausal morbidly obese women (BMI ranging 37-62 kg/m2) before, 6, 12 and 24 months after LASGB. Total body water (TBW), fat-free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance analysis; tissue hydration was also assessed by impedance vector analysis. At study ending, the subjects had a total weight loss of 28% of baseline body weight (15% after 6 months). After LASGB, weight loss was mainly due to decreased FM, and TBW, FFM, and body hydration were not significantly reduced. Weight loss was associated with an 82% rise in serum DHEAS already after 6 months while cortisol, cortisol/DHEAS molar ratio, and insulin levels fell by 5.5, 62 and 50%, respectively, after 6, 12 and 24 months (p<0.05). CONCLUSIONS: LASGB associated with a well balanced low-calorie diet permits a satisfactory 2-yr weight loss, sparing FFM and without body fluid alterations. As the result of a stable weight reduction program weight loss is associated to decrease in cortisol, cortisol/DHEAS molar ratio, and insulin plasma levels with marked rise in DHEAS. Higher cortisol/DHEAS molar ratio values at baseline are also associated to lower weight loss after LASGB, with lower decrease in FM and higher reduction in FFM and body cell mass, in spite of no differences in dietary regimes. Cortisol/DHEAS molar ratio is likely to represent a reliable marker of favourable modifications in body composition.

Adult↗

Evidence for altered adipocyte function in polycystic ovary syndrome.

BACKGROUND: Adipocytokines are produced by adipose tissue and have been thought to be related to insulin resistance and other health consequences. We measured leptin, adiponectin, and resistin simultaneously in women with polycystic ovary syndrome (PCOS) and age- and weight-matched controls. Our hypothesis was that these simultaneous measurements would help determine whether adipocytokine secretion is abnormal in PCOS independent of body mass and whether these levels are related to insulin resistance as well as other hormonal changes. METHODS: Fifty-two women with PCOS and 45 normal ovulatory women who were age- and weight-matched were studied. Blood was obtained for adipocytokines (leptin, adiponectin, and resistin) as well as hormonal parameters and markers of insulin resistance as assessed by the quantitative insulin-sensitivity check index. Body mass index (BMI) was stratified into obese, overweight, and normal subgroups for comparisons between PCOS and controls. RESULTS: Adiponectin was lower (P < 0.05) and resistin was higher (P < 0.05) while leptin was similar to matched controls. Breakdown of the groups into subgroups showed a strong body mass relationship for leptin with no changes in resistin although adiponectin was lower in PCOS, even controlling for BMI. In controls, leptin and adiponectin and leptin and resistin correlated (P < 0.05) but not in PCOS. In controls, all adipocytokines correlated with markers of insulin resistance but not in PCOS. CONCLUSIONS: When matched for BMI status, decreased adiponectin in PCOS represent the most marked change. This alteration may be the result of altered adipose tissue distribution and function in PCOS but no correlation with insulin resistance was found.

Adipocytes↗

Is ovulation induction still a therapeutic problem in patients with polycystic ovary syndrome?

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases affecting women of fertile age, and is characterized by hyperandrogenism, chronic anovulatory cycles and oligomenorrhea or amenorrhea. Given the repercussions of chronic anovulation on sterility, PCOS is a heavy social burden. Here we describe the procedures used to induce ovulation in PCOS patients, the surgical approach and medical treatments that are still being experimented.

Aromatase Inhibitors↗

Adrenal adenoma and normal androgen levels in a young woman with polycystic ovaries: a case of idiopathic hirsutism?

A case of unusual combination of polycystic ovaries (PCO), adrenal non-functioning adenoma and severe hirsutism in a young woman from Southern Italy is reported here. A 18-yr-old woman was referred to our Department because of oligomenhorrea, acne and severe hirsutism. During evaluation of the cause of her symptoms, PCO and small left adrenal adenoma were revealed. Although adrenal androgen excess has been shown to dysregulate the hypothalamic-pituitary-gonadal axis, causing PCO-like syndrome, normal circulating androgen values were found. Androgens and cortisol levels were completely suppressed by low-dose dexamethasone test, excluding autonomous steroid secretion by the adrenal mass. Normal response of cortisol and adrenal androgens to corticotropin stimulation test permitted the exclusion of functional adrenal hyperandrogenism. Despite normal LH/FSH ratio, anovulatory cycles were revealed by persistently low progesterone values. Glucose and insulin response to oral glucose tolerance test did not differ from those of normal population. The patient showed an improvement of acne and hirsutism on therapy with estro-progestins (EP). In conclusion, despite normal pattern of serum androgens and LH/FSH ratio, this patient had anovulatory cycles and good response to the EP treatment. These findings suggest that ultrasonography evidence of PCO together with anovulatory cycles contributed to her clinical picture whereas adrenal adenoma seemed to have no relevant role. This case report underlines the need of cautious interpretation of imaging results and clinical signs of severe hirsutism, reminding one that the true cause of a medical problem may not be the most evident.

Acne Vulgaris↗

[Polycystic ovary syndrome in pubertal period: clinical, biological, metabolic and genetic polymorphism].

Polycystic ovary syndrome (PCOS) is a common cause of hyperandrogenism in adolescent girls. In its complete post menarchal expression, the syndrome is characterized by the association of typical clinical, biological, and ultrasonographic findings. Many factors have contributed to our knowledge of different clinical forms of PCOS in adolescent girls. They are helpful for clarifying misleading situations in a period of life when diagnosis of PCOS implies a treatment for many years and may interfere with gynecological outcome. During the last 3 years, we had the opportunity to manage in our unit 45 adolescent girls with ovarian hyperandrogenism: 32 of them had PCOS and the other 13 functional ovarian hyperandrogenism defined by clinical and biological hyperandrogenism without ultrasonographic abnormality. In this review, we report, from our personal experience as well as from recent literature data, the different clinical expressions of PCOS in the pubertal period: the classical post menarchal form, the exceptional pre menarchal form, the post precocious pubarche and the post precocious puberty forms, the familial expression as well as the dominant metabolic expression.

Adolescent↗

Screening a coastal population in Southern Italy: iodine deficiency and prevalence of goitre, nutritional aspects and cardiovascular risk factors.

BACKGROUND AND AIM: To evaluate the prevalence of goitre by means of urinary iodine excretion, palpatory and ultrasonographic thyroid examinations in a heterogeneous population living by the sea. METHODS AND RESULTS: We used a special self-administered questionnaire to evaluate thyroid size, iodine intake, eating habits and cardiovascular risk factors in 600 subjects with a mean age of 45 +/- 17 years: 253 men (42.3%) and 347 women (57.7%). Urinary iodine excretion was low (72.1 +/- 15.7 microg/L; median 71.2) and associated with ultrasonographic evidence of an enlarged thyroid (16%) or structural thyroid abnormalities (30%), thus allowing us to define the Salerno Gulf as a mild-moderate area of endemic goitre. All of the subjects ate a Mediterranean diet, with a mean of two portions of fish/week. The cardiovascular risk factors considered were obesity, cigarette smoking, hypertension, hypercholesterolemia, hypertriglyceridemia and diabetes, the prevalences of which were in line with those reported in other studies of similar age-matched populations. CONCLUSIONS: The moderate intake of fish and the consumption of a Mediterranean diet did not prevent goitre. Iodine deficiency and subsequent goitre endemia are also present at sea level, probably because of a diet based on local products grown on soil with a low iodine content or possible seawater, soil and air environmental pollution that may interfere with the availability of iodine. The assessment of iodine deficiency should therefore involve the entire population and not only subjects living far from the sea.

Adult↗

Beneficial treatment with risedronate in long-term survivors after allogeneic stem cell transplantation for hematological malignancies.

In this prospective randomized study we evaluated the effect of risedronate, an aminobisphosphonate, on bone mass and turnover in patients who had undergone allogeneic stem cell transplant (SCT) for hematological malignancies. Thirty-four patients (18 females, 16 males, age 32+/-10 years) with bone mineral density (BMD) </=-1.5 SD as a T-score at least 6 months after SCT were treated with calcium 1 g/day and vitamin D 800 IU/day and randomized to receive ( n=17, group 1) or not receive ( n=17, group 2) oral risedronate 5 mg/day. The duration of treatment was 12 months. After 6 months, lumbar BMD increased by 4.4+/-1.6% in patients of group 1 and decreased by 4.3+/-1.5% in those of group 2 ( P<0.05); at the femoral neck, BMD did not change significantly in patients of group 1 (+1.2+/-1.2%), while it decreased in those of group 2 (-4.3+/-2.1%; P<0.05). After 12 months, lumbar BMD further increased (+5.9+/-1.7%, P<0.05), compared to baseline in group 1 and slightly increased (+1.1+/-1.4%) in group 2. No further changes were observed at femoral neck in both groups. In conclusion, treatment with risedronate for 12 months increased BMD significantly at the lumbar spine and prevented further bone loss at the femoral neck in long-term survivors after allo-SCT.

Administration, Oral↗

GH release after GHRH plus arginine administration in obese and overweight women with polycystic ovary syndrome.

Few and unclear data are available in the literature about the relationship between impairment of GH/IGF-I axis and polycystic ovary syndrome (PCOS). This study was aimed to evaluate the basal GH and IGF- levels, and GH release after challenge test in obese and overweight women with PCOS. Thirty patients with PCOS and other 30 healthy women matched for age, body mass index (BMI) and waist-hip ratio (WHR) were studied. Serum follicle-stimulating hormone (FSH), LH, PRL, E2, P, 17OH-progesterone (17OH-P), total T, delta4, DHEA-S, SHBG, GH and IGF-I levels were evaluated in each subject. A GHRH plus arginine challenge test was performed in all subjects. After provocative test, in PCOS and control women the GH levels were significantly (p<0.05) higher in comparison to basal values from 30 min to 120 min. At the same times, a significant (p<0.05) difference was observed between women with PCOS in comparison to healthy women. The mean peak value of GH resulted significantly (p<0.05) lower in PCOS women in comparison to healthy women. The total GH response (area under curve, AUC) to GHRH plus arginine test resulted significantly (p<0.05) lower in PCOS than in healthy women. These findings were statistically significant (p<0.05) also considering the distinction in obese and overweight women. The AUC for GH secretion was significantly lower (p<0.05) in obese in comparison to overweight subjects in the control group, whereas no significant difference was detected between obese and overweight women in the PCOS group. In conclusion, in PCOS women there is a BMI-independent alteration of the GH levels. Further investigations will be necessary to establish the real cause of these data.

17-alpha-Hydroxyprogesterone↗

Early carotid atherosclerosis in normotensive severe obese premenopausal women with low DHEA(S).

The aim of this study was to investigate the direct involvement of hyperinsulinaemia, DHEA and DHEA-S [DHEA(S)] in severe obesity in early carotid atherosclerosis, measured as intima-media thickness (IMT). Seventeen normotensive premenopausal women with very high BMI (43.5 +/- 1.6 kg/m2) were recruited for the study. Six women were also evaluated 12 months after laparoscopic adjustable silicone gastric banding (LASGB). Dietary intake, fasting plasma lipid profile, glycemic and insulinemic response to the OGTT, adrenal secretion, at baseline and after ACTH stimulation test, were measured. IMT, common carotid diameter (CD) and left ventricular mass index (LVMi) were measured by B-mode echotomography. All obese subjects showed higher fasting and stimulated insulin levels, but lower DHEA(S) levels than controls, showing a negative correlation between both fasting and stimulated insulin and DHEA(S), either at baseline or after ACTH testing. IMT was higher (p < 0.05) than controls, with a positive correlation with stimulated insulin (p < 0.05) and a strong negative correlation with DHEA(S) (p < 0.001). In a multiple linear regression analysis, insulin response to OGTT maintained an association with DHEA(S) independent of fasting insulin, while DHEA maintained the association with IMT independent of stimulated insulin (p < 0.0001). In the six patients evaluated 12 months after LASGB, fasting insulin levels decreased, while DHEA(S) levels increased (p < 0.05). In conclusion, an early cardiovascular involvement was detected in this group of severe obese with hyperinsulinaemia and low DHEA(S), even in the absence of other well known CVD risk factors.

Adult↗

Lymphocyte subset pattern in acromegaly.

Immune function in acromegalic patients has been poorly investigated. The aim of this study was to evaluate the main surface antigen clusters of circulating lymphocytes in acromegaly. One hundred patients with active acromegaly (55 women and 45 men, aged 20-70 yr) and 200 healthy subjects sex- and age-matched with the patients (110 women and 90 men, aged 20-70 yr) were enrolled in this study. All patients and controls were born and live in Southern Italy. No patient had received octreotide, bromocriptine or corticosteroids for at least 3 months before entering the study. The analysis of lymphocyte subset pattern was performed by flow cytometry and fluorescein isothiocyanate or phycoerythrin directly conjugated monoclonal antibodies specific for the cell surface antigen clusters (CD) representing T-cell population as a whole (CD3), T helpers (CD4), T suppressors (CD8), natural killer cells (CD16) and B-cell population as a whole (CD19). Acromegalics had significantly increased levels of CD3 (67.1+/-7.2 vs 64.3+/-8.8%; p=0.03) and CD4 (37.8+/-3.5 vs 36.4+/-4.3%; p=0.004) and decreased levels of CD8 (31.4+/-3.3 vs 33.7+/-8.2%; p<0.01) and CD19 (12.1+/-3.1 vs 15.2+/-5.1; p=0.01) without age-difference. The results of the current study demonstrate an increase in T-cell activity together with a decrease in B-cell activity in a very large series of patients with active acromegaly. These data further support the existence of abnormalities of the immune system in patients with chronic GH/IGF-1 excess.

Acromegaly↗

Human prostatic cell line PNT1A, a useful tool for studying androgen receptor transcriptional activity and its differential subnuclear localization in the presence of androgens and antiandrogens.

The human immortalized prostatic cell line PNT1A has been proved to be a good model for analysis of cellular processes such as the prostatic epithelium proliferation in response to androgens and growth factors. Here we used this cell line for studying the transcriptional activity and trafficking of the androgen receptor (AR) by analyzing several actions of antiandrogens. Transient transfection experiments with PNT1A cells were performed with wild type human AR and an androgen-responsive gene reporter. We demonstrated that the transcription of reporter gene could be triggered by natural androgens (testosterone and dihydrotestosterone) in PNT1A cells as well as in the prostatic carcinoma cell line DU-145. With competitive experiments in the two cell lines, we observed no difference between the antagonistic capacity of cyproterone acetate (CPA) and hydroxyflutamide at 10(-7) M. At this concentration, bicalutamide antagonist activity was lower. In parallel, we compared the subcellular localization of the modified green fluorescent protein (EGFP)-AR in COS-7, PNT1A and DU-145 cell lines under fluorescence microscopy: we found different distributions between nucleus and cytoplasm, depending on the cell line and the culture medium. Androgen induced cluster formation within the nucleus of the PNT1A and DU-145 cells. However, the cytonuclear trafficking of androgen bound EGFP-AR in the same living cell and nuclear foci were easier to examine in the PNT1A cells. The antiandrogen capacity of bicalutamide was manifested by a slower androgen-dependent nuclear transfer of EGFP-AR and a homogeneous nuclear localization. A delayed advent of nuclear clusters was observed in presence of CPA. We conclude that the PNT1A cell line is a better model than the DU-145 cell line to analyze the trafficking of AR and the association of AR on the nuclear matrix, as well as to observe the action of antiandrogens on these critical steps in prostate cells.

Active Transport, Cell Nucleus↗

Spine abnormalities and damage in patients cured from Cushing's disease.

The skeletal system is a common target of glucocorticoids. Structural and functional impairment of skeletal system is a relevant cause of morbidity and disability in patients with Cushing's syndrome. Thirty-six patients long-term (3.9 +/- 0.5 yrs) cured from Cushing's disease (CD), 26 with adulthood-onset CD (AOCD) and 10 with childhood-onset CD (COCD) and 2 groups of controls, 24 age- and sex-matched patients with nonfunctioning pituitary adenomas (NFA) and 36 age- and sex-matched healthy subjects (HS), entered this open transversal controlled study to evaluate the prevalence of spine abnormalities and damage by standard radiography in subjects with a history of Cushing's syndrome. Symptoms and signs of backache were present in 86.1% CD patients (100% COCD and 80.8% AOCD), in 30.5% HS (chi2 = 20.6, p < 0.0001) and 37.5% NFA patients (chi2 = 13.2, p < 0.0001). The prevalence of trabecular bone rarefaction (chi2 = 6.5, p < 0.01 and chi2 = 4.5, p < 0.05), vertebral collapse (chi2 = 10.7, p < 0.01 and chi2 = 7.0, p < 0.01) and scoliosis (chi2 = 10.9, p < 0.01 and chi2 = 11.1, p < 0.01) resulted significantly increased in CD patients as compared both to HS and NFA patients. In CD patients, the number of collapsed vertebral bodies was significantly correlated to age of disease onset (r = -0.63, p < 0.0001), disease duration (r = 0.33, p < 0.05) and urinary free cortisol levels at disease diagnosis (r = 0.72, p < 0.0001). The prevalence of cortical bone sclerosis was significantly increased in AOCD than in HS (chi2 = 6.5, p < 0.01) and COCD (chi2 = 7.7, p < 0.01) whereas that of trabecular bone rarefaction was significantly higher in COCD patients than in HS (chi2 = 18.3, p < 0.0001), NFA (chi2 = 14.2, p < 0.0001) and AOCD patients (chi2 = 9.1, p < 0.01). Patients cured from CD have increased prevalence of spine damage, mostly when the disease developed before the completion of skeletal growth. Therefore, a periodical radiological follow-up of the skeleton and a specific treatment for the bone damage should be included in the management of patients with Cushing's syndrome.

Adult↗

Growth hormone secretion after baclofen administration in different phases of the menstrual cycle in healthy women.

AIM: The aim of this study was to investigate the effect of baclofen administration on growth hormone (GH) secretion during different phases of the menstrual cycle. METHODS: Twelve healthy women (33.6 +/- (SD) 2.8 years; range 23-40 years) with regular menstrual cycles were enrolled. The phases of the menstrual cycle were determined using transvaginal ultrasonography (TV-US) and detecting hormonal serum levels. Plasma GH levels were evaluated during the early follicular, periovulatory and luteal phases of the cycle before and after the baclofen challenge test. RESULTS: After acute baclofen administration, GH levels increased significantly (p < 0.001) compared to basal values during the periovulatory and luteal phases, while no significant variation was detected during the early follicular phase. In addition, plasma GH levels resulted significantly (p < 0.001) higher during the luteal phase than during the periovulatory phase. CONCLUSION: Acute baclofen administration induces a significant increase in plasma GH levels in healthy females during the periovulatory and luteal phases, but not during the early follicular phase. These data suggest a modulator role of plasma sex steroids levels on GH release induced by baclofen.

Administration, Oral↗

A stable prostatic bioluminescent cell line to investigate androgen and antiandrogen effects.

We developed a new stable prostatic cell line expressing the human androgen receptor (AR) and the AR-responsive reporter gene to generate a powerful tool for investigating androgen action and for rapid screening of agonists and antagonists. The AR-deficient PC-3 cells were stably transfected with pSG(5)-puro-hAR and pMMTV-neo-Luc. After selection with puromycin and neomycin, one highly inducible clone was isolated and named PALM, for PC-3-Androgen receptor-Luciferase-MMTV. The expression of hAR was confirmed by western blot and steroid-binding assays on the whole cells. The transcriptional activity of the clone was measured after incubation of cells with increasing concentrations of synthetic R1881 or natural androgens (DHT and testosterone). The three agonists had the same maximal activity at 0.1 microM and the fold induction was equal to 20. The agonist and antagonist activities of the steroidal antiandrogens (cyproterone acetate and RU2956) and the non-steroidal antiandrogens (nilutamide, bicalutamide, inocoterone and hydroxyflutamide) measured with the PALM cells were in good correlation with the results obtained with transiently transfected cells. The selectivity in steroid transactivation was demonstrated with estradiol, progesterone, cortisol, dexamethasone and aldosterone. Spironolactone and RU486 showed partial agonist and antagonist activities, whereas R5020 presented only a partial antagonist activity. We here demonstrate that this stable transfectant provides an accurate tool for studying wild-type human AR activation and its regulation by androgens and antiandrogens in a human prostatic epithelial cell, which is routinely available and remains androgen-responsive in vitro.

Androgen Antagonists↗