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Graziano DEL RIO

Ricercatore Universitario
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto

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Pubblicazioni

2011 - Le strade della bandiera [Monografia/Trattato scientifico]
Melloni, Alberto; Bruni, Emanuela; Delrio, Graziano
abstract

Per le celebrazioni del 150° dell'Unità d'Italia (1861-2011) Reggio Emilia città del Tricolore ha trasformato le strade del suo centro in un museo dove sono esposte le bandiere che hanno scandito le tappe della storia nazionale: da quelle della Rivoluzione francese a quelle napoleoniche, da quelle delle insurrezioni e degli stati preunitari alle bandiere delle guerre di indipendenza e delle spedizioni garibaldine, fino a quelle del Regno d'Italia, della Resistenza e della Costituzione repubblicana. Ogni bandiera ha una sua vicenda, un suo senso, una sua storia che viene qui richiamata per accompagnare il lettore fino all'articolo 12 della nostra carta fondamentale, che senza enfasi e senza esitazione indica nel Tricolore la bandiera dello Stato italiano come ultimo dei principi fondamentali della Costituzione.

2004 - Systematic study of long-term stability of 3,4-dihydroxyphenylglycol in plasma for subsequent determination with liquid chromatography [Articolo su rivista]
Venneri, Mg; DEL RIO, Graziano
abstract

The effect of three storage temperature levels (i.e. +4, -20 and -80degreesC) and time intervals from sampling (3, 6 and 9 months) on the degradation of 3,4-dihydroxyphenylglycol (DHPG) and norepinephrine (NE) was investigated in a systematic study. Extracted human plasma samples and acidified standard solutions were stored for long periods (up to 9 months) without the addition of any stabilizing agent. DHPG and NE values, determined using a ion-pair reversed-phase high-performance liquid chromatography method with electrochemical detection of coulometric type (IP-RP-HPLC-CD), remained constant over time in those plasma samples and standard solutions that had been stored at the lowest storing temperature (i.e. -80degreesC). The expected degradation was observed at higher temperature levels. Plasma and standard DHPG degradation can, therefore, be prevented by storing samples at a lower temperature than previously suggested with no need to add any stabilizing agent.

2002 - Cortisol and ACTH response to oral dexamethasone in obesity and effects of sex, body fat distribution, and dexamethasone concentrations: A dose-response study [Articolo su rivista]
Pasquali, R; Ambrosi, B; Armanini, D; Cavagnini, F; Uberti, Ed; DEL RIO, Graziano; de Pergola, G; Maccario, M; Mantero, F; Marugo, M; Rotella, Cm; Vettor, R.
abstract

There is increasing evidence that the abdominal obesity phenotype may be associated with multiple alterations of the hypothalamic-pituitary-adrenocortical (HPA) axis activity in both sexes. Our hypothesis is that the lack of adequate cortisol suppression after the dexamethasone test may constitute an indirect marker of HPA axis hyperactivity in the presence of the abdominal obesity phenotype. A total of 34 normal-weight (13 men and 21 women) and 87 obese (36 men and 51 women), healthy, nondepressed subjects therefore underwent four different dexamethasone suppression tests randomly performed at varying intervals of at least 1 wk between each test. After a standard overnight 1-mg dexamethasone test, which served as a reference, three other tests were randomly performed at 1-wk intervals by administering 0.0035, 0.0070, and 0.015 mg oral dexamethasone per kilogram of body weight overnight. Blood samples were obtained for cortisol, ACTH, and dexamethasone. Results were analyzed separately in men and women as well as in normal-weight [body mass index (BMI) less than or equal to25 kg/m(2)] and overweight or obese (BMI <25 kg/m(2)) subjects. The waist circumference and the waist to hip ratio (WHR) were used as markers of body fat distribution. After the standard 1-mg test, cortisol suppression was greater than 90% in all subjects. However, after each test, obese women had significantly higher values of percent cortisol and percent ACTH suppression than normal-weight women without any difference between obese and normal-weight men. Considering the response to the three variable-dose tests, a clear dose-reponse pattern (P < 0.001 for trend analysis) in percent cortisol and percent ACTH suppression was found in all subjects. After each test men had significantly higher dexamethasone levels than women, regardless of BMI. However, obese women, but not men, had significantly higher dexamethasone levels after each test than their normal-weight counterpart. Plasma dexamethasone concentrations were dose related (P < 0.001 for trend analysis) in all subjects, but the dose-related increase was significantly higher in normal-weight men than normal-weight women, whereas it was similar in obese subjects of both sexes. Stepwise multiple regression analysis revealed that both percent cortisol and percent ACTH variations were significantly and negatively influenced by dexamethasone levels, as well as by waist circumference values in men, and independently by BMI and waist circumference in women. However, in contrast to what has been found in men, a divergent contribution of BMI and waist circumference was found in women indicating that, with increasing waist values, a smaller suppression of the HPA axis was found with respect to that expected on the basis of BMI values. In conclusion, this study provides data of both physiological and physiopathological relevance. Overall, our data indicated that adjustment of the dexamethasone dose to body weight does not seem to substantially improve the sensitivity of the test, even in obese individuals, particularly when near-maximal doses are administered. However, this study demonstrated a highly significant effect of dexamethasone blood level concentrations on cortisol and ACTH suppression to low-dose dexamethasone tests. In addition, a significant effect of gender on postdexamethasone cortisol concentrations, suppression of the HPA axis, and dexamethasone levels were found, which may be dependent on related differences in both cortisol and dexamethasone metabolism. We showed that pituitary sensitivity to feedback inhibition by dexamethasone is preserved in obesity in both sexes even at low dosages. On the other hand, our data suggest that, at least in women, abdominal fat distribution may partially counteract the progressively greater suppressibility of the HPA axis that would be expected according to increasing BMI.

2000 - Adrenomedullary function and its regulation in obesity [Articolo su rivista]
DEL RIO, Graziano
abstract

Sympathoadrenal system (SAS) represents a major contributor to body homeostasis, regulating blood pressure heart rate, energy balance and intermediary metabolism. Thus, it is not unexpected that in last decades a consistent literature has been focused on the possible role of sympathoadrenal system in the pathogenesis of human obesity. There are, however, many factors confounding comparison of sympathoadrenal system activity between lean and obese subjects. Among these, one should be aware that SAS should be functionally separated into sympathetic nervous system (SNS) and adrenal medulla (AM), and that each of these two systems can be activated independently from the other by distinct physiological stimuli; this phenomenon in fact underlies the discordant pattern of findings for adrenomedullary and sympathetic activity in human obesity. While, in fact, obese subjects often display an increased basal SNS activity, there are numerous reports of blunted AM function in obese. Recent evidence suggests that this reduced adrenaline secretion is an acquired feature of human obesity, a finding that fits in well with the hypothesis that hormonal mileu, particularly sex steroids and cortisol, plays a role in the determination of blunted AM activity. Catecholamines have been recently demonstrated to play a role also in the regulation of whole energy balance. Adrenaline in fact acutely reduces both leptin mRNA as well as circulating leptin in human obese subjects, suggesting that catecholamines may influence the cross-talk between energy stores and the centrally mediated modulation of food intake. In summary, the study of adrenomedullary function and of possible mechanisms of its disturbances in human obesity, appears of great interest, and surely deserves further investigations.

2000 - Baseline and stimulated catecholamine secretion in normotensive patients with active acromegaly: acute effects of continuous octreotide infusion [Articolo su rivista]
DEL RIO, Graziano; Velardo, Antonino; C., Mascadri; G., Zalteri; G., Papi; R., Menozzi; A., Giustina
abstract

Objective: Alterations in catecholamine plasma levels may contribute to the cardiovascular complications of acromegaly. Since few data are available on the catecholamine secretory dynamics in active acromegaly and no evidence exists on catecholamine variations during GH decrease, we studied acromegalic patients before and during octreotide administration. Methods: Mie evaluated the catecholamine responses to upright posture and a cold pressure test (CPT) in 11 acromegalic (A) patients before and during continuous administration of octreotide (500 mu g/24 h by s.c. pump) compared with 11 normal(N) subjects. Results: All the acromegalic patients showed left ventricular cardiac hypertrophy. The cardiovascular responses to upright posture were similar between normal subjects and acromegalics both before and during octreotide treatment, The basal levels of norepinephrine (NE) were significantly higher in A patients compared with N subjects (423 +/- 45 vs 264 +/- 32 pg/ml, P < 0.05) and decreased during therapy (291 +/- 32 pg/ml: P < 0.01). The increase in plasma NE during upright posture was significantly lower in A than in N subjects (P < 0.01), but was restored to normal during octreotide treatment. CPT increased systolic and diastolic blood pressure, pulse rate and NE plasma levels in N (P < 0.05) but not in A subjects both before and during octreotide treatment. Conclusions: Our data demonstrate the presence of increased basal NE levels in acromegalic patients with a defective sympathetic response to stimuli. Short-term octreotide infusion is able to induce a reduction in the basal levels of NE and a normalization of the catecholamine response to posture.

2000 - Influence of exogenous melatonin on catecholamine levels in postmenopausal women prior and during oestradiol replacement. [Articolo su rivista]
Cagnacci, Angelo; A. L., Zanni; M. G., Veneri; R., Menozzi; Volpe, Annibale; G. D., Rio
abstract

In young individuals melatonin administration reduces circulating norepinephrine. Some effects of melatonin are reduced in elderly women and are modulated by gonadal steroids. Accordingly, the influence of melatonin on catecholamine levels was investigated in postmenopausal women without and with oestradiol replacement.Prior to and after 2 months of transdermal oestradiol (50 microg/day), women were studied on two consecutive days, on which they received placebo or 1 mg of melatonin orally in a randomised and double-blind fashion.Fourteen healthy postmenopausal women.Resting levels of epinephrine and norepinephrine and their responses to both a cold stimulus, performed by placing a hand in a basin of water and ice for 2 minutes, and to 10 minutes of upright position (upright test).Prior to oestradiol, melatonin did not modify baseline or stimulated catecholamine levels. In contrast, during oestradiol, melatonin tended to reduce, although not significantly, baseline norepinephrine levels (P = 0.053), and significantly reduced peak values (P = 0.0061) and integrated norepinephrine response (P = 0.0076) to the cold stimulus. Responses of norepinephrine to the upright test were not modified, while those of epinephrine were increased (P = 0.042). During, but not prior to oestradiol replacement, modifications induced by melatonin (melatonin day-placebo day) in the norepinephrine response to the cold (r2 = 0. 457; P = 0.0079) and the upright (r2 = 0.747; P = 0.0001) tests were linearly and inversely related to the responses of the placebo day.Melatonin does not modulate adrenergic activity in postmenopausal women without hormone replacement therapy. Oestradiol replacement restores the capability of melatonin to modulate adrenergic activity, particularly the norepinephrine response to stimuli.

2000 - Metabolic effects of fluoxetine in obese menopausal women [Articolo su rivista]
Bondi, M; Menozzi, R; Bertolini, M; Venneri, Mg; DEL RIO, Graziano
abstract

Our objective was to assess thermogenic action of fluoxetine (FL) in obese menopausal women, evaluating the effect of FL administration on resting energy expenditure (REE) and on glucose-induced thermogenesis both after acute administration (40 mg in single dose the evening before measurements) and after a 12- week period of diet treatment plus FL (60 mg per day) or placebo. It was a double-blind, placebo-controlled design both in acute and in chronic study. The subjects were 32 obese, otherwise healthy, menopausal women. The patients were assigned randomly to three groups, one performing an acute study protocol, in which resting and glucose-induced thermogenesis was measured after FL and placebo administration, performed in randomised order. The other two groups underwent dietary plus pharmacological treatment (FL or placebo, FL). Resting and glucose-induced thermogenesis was measured at baseline and after 12 weeks of treatment. The results showed that acute FL administration caused an increase in resting energy expenditure (PL: 5.35+/-0.18 vs FL: 5.53+/-0.24 KJ/min, p<0.05). A significant decrease of REE was observed in the PL group after 12 weeks (p<0.03), while a slight, but not significant, decrease was observed in the FL group (p=NS). FL did not affect thermic response to oral glucose neither after acute nor chronic administration (p=NS for all groups studied). The conclusion was that our data give support to thermogenic actions of FL after acute administration, suggesting also that chronic FL treatment may restrain to some degree the metabolic adaptation expected during weight loss in obese subjects. At variance with what observed with other drugs, such as dexfenfluramine, an increased thermic effect of oral glucose does not seem to be involved in the thermogenetic action of FL.

2000 - Sympathoadrenal response of postmenopausal women prior and during prolonged administration of estradiol [Articolo su rivista]
Cagnacci, Angelo; A. L., Zanni; M., Bondi; Volpe, Annibale; Menozzi, Renata; DEL RIO, Graziano
abstract

Cardiovascular disease seems to increase after the menopause and is thought to be reduced by estrogen replacement therapy. Among the many studies which have tried to define the multifactorial mechanisms of estrogens cardiovascular prevention, very few have focused on their possible modulation of adrenergic activity. In the present study we investigated whether prolonged estradiol replacement via transdermal patches is able to modulate cardiovascular and adrenergic responses to stimuli.Baseline and responses to a cold stimulus and to the upright position of catecholamines (epinephrine and norepinephrine), heart rate, systolic and diastolic blood pressure were investigated in 15 healthy volunteer postmenopausal women both prior to and after 2 months of treatment with patches rated to deliver 50 microg/day of estradiol.Basal norepinephrine levels (P<0.005), as well as their integrated responses to the cold stimulus (P<0.02) were lower during estradiol. By contrast, responses of norepinephrine to the upright test, as well as basal and responses to stimuli of epinephrine and circulatory parameters were not different before and during estradiol.Estradiol replacement at low doses significantly decreases overall sympathetic output, both in basal conditions and under specific stimuli. These effects whether maintained or magnified in the long term may play a role in the prevention of the postmenopausal cardiovascular risk.

2000 - The effects of transdermal estradiol on the response to mental stress in postmenopausal women: A randomized trial [Articolo su rivista]
Ceresini, G; Freddi, M; Morganti, S; Rebecchi, I; Modena, Ab; Rinaldi, M; Manca, C; Amaducci, A; DEL RIO, Graziano; Valenti, G.
abstract

PURPOSE: Estrogens inhibit adrenomedullary catecholamine release and catecholamine-mediated responses to stress. We examined whether estrogen supplementation reduces the sympathoadrenal response to mental stress in postmenopausal women. MATERIALS AND METHODS: We compared the effects of 3-week treatment with transdermal 17-beta-estradiol and placebo in 10 postmenopausal women using a randomized, blinded, crossover design. We measured plasma catecholamine levels and the cardiovascular and metabolic responses to a 15-minute stress with mental arithmetic. Treatments were compared using repeated measures analysis of variance. RESULTS: During placebo treatment, mean (+/- SD) epinephrine levels reached a peak of 431 +/- 135 pmol/liter after 15 minutes of stress; the epinephrine response was blunted during estradiol treatment, with a peak of 357 +/- 77 pmol/liter (P &lt;0.05). Estradiol also blunted the diastolic blood pressure response to stress (baseline levels of 78 +/- 15 mm Hg vs peak of 90 +/- 6 mm Hg during placebo; baseline of 80 +/- 8 mm Hg vs peak of 84 +/- 6 mm Hg during estradiol; P &lt;0.05). Estradiol treatment also blunted the decrease in the standard deviation of the mean of the electrocardiographic RR intervals and the increase in the ratio between the low-frequency and high-frequency bandwidths. CONCLUSION: We observed a moderate, although significant, reduction in markers of the stress response to mental arithmetic in postmenopausal women treated with transdermal 17-beta-estradiol. Am J Med. 2000;109:463-468.

1999 - Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans [Articolo su rivista]
Bisi, G; Podio, V; Valetto, Mr; Broglio, F; Bertuccio, G; DEL RIO, Graziano; Arvat, E; Boghen, Mf; Deghenghi, R; Muccioli, G; Ong, H; Ghigo, E.
abstract

Reduced cardiac mass and performances are present in GH deficiency and are counteracted by rhGH replacement. GH and IGF-I possess specific myocardial receptors and have been reported able to exert an acute inotropic effect. Synthetic GH secretagogues (GHS) possess specific pituitary and hypothalamic but even myocardial receptors. In 7 male volunteers, we studied cardiac performance by radionuclide angiocardiography after iv administration of rhGH or hexarelin (HEX), a peptidyl GHS. The administration of rhGH or HEX increased circulating GH levels to the same extent (AUC: 1594.6+/-88.1 vs 1739.3+/-262.2 mu g/l/min for 90 min) while aldosterone and catecholamine levels did not change; HEX, but not rhGH, significantly increased cortisol levels. Left ventricular ejection fraction (LVEF), mean blood pressure (MBP) and heart rate (HR) were unaffected by rhGH (62.4+/-2.1 vs 62.1+/-2.3%, 90.6+/-3.4 vs 92.0+/-2.5 mm Hg, 62.3+/-1.8 vs 66.7+/-2.7 bpm). HEX increased LVEF (70.7+/-3.0 vs 64.0+/-1.5%, p&lt;0.03) without significant changes in MBP and HR (92.8+/-4.7 vs 92.4+/-3.2 mmHg, 63.1+/-2.1 vs 67.0+/-2.9 bpm). LVEF significantly raised at 15 min, peaked at 30 min and lasted up to 60 min after HEX. These findings suggest that in man, the acute administration of Hexarelin exerts a short-lasting, positive inotropic effect. This effect seems GH-independent and might be mediated by specific GHS myocardial receptors. (J. Endocrinol. Invest. 22: 266-272, 1999) (C)1999, Editrice Kurtis.

1999 - Adrenomedullary response to caffeine in prepubertal and pubertal obese subjects [Articolo su rivista]
M., Bondi; G., Grugni; Velardo, Antonino; O., Biella; Mg, Venneri; F., Morabito; R., Menozzi; DEL RIO, Graziano
abstract

OBJECTIVE: To investigate whether blunted adrenomedullary responsiveness to stimuli is a primary feature of human obesity in childhood and adolescence DESIGN: Comparison of plasma catecholamine response to caffeine in obese and lean subjects before and after puberty onset. SUBJECTS: Twelve lean prepubertal subjects (six males and six females), 15 prepubertal obese subjects (seven males and eight females), 12 pubertal lean subjects (six males and six females) and 24 pubertal obese subjects (12 males and 12 females). MEASUREMENTS: Plasma levels of Luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17 beta-estradiol and testosterone were used to validate Tanner score. Systolic and diastolic blood pressure, pulse rate and plasma catecholamines before and after caffeine administration (4 mg/kg of ideal body weight). RESULTS: Caffeine administration significantly stimulated adrenaline release in all subjects studied. The incremental area of adrenaline response to caffeine, analysed by multiple comparison test, was lower in pubertal obese subjects with respect to other groups. CONCLUSIONS: At variance with what is observed in adulthood obesity, prepubertal obese subjects show an intact adrenomedullary response to caffeine.

1999 - Cardiac effects of hexarelin in hypopituitary adults [Articolo su rivista]
Bisi, G; Podio, V; Valetto, Mr; Broglio, F; Bertuccio, G; Aimaretti, G; Pelosi, E; DEL RIO, Graziano; Muccioli, G; Ong, H; Boghen, Mf; Deghenghi, R; Ghigo, E.
abstract

Growth hormone (GH)-releasing peptides possess specific pituitary, hypothalamic, and myocardial receptors. Seven adult male patients with GH deficiency (GHD) (age, mean +/- S.E.M.: 42.0 +/- 4.0 year) were studied by equilibrium radionuclide angiocardiography after i.v. administration of hexarelin, a peptide GH secretagogue. Data for these patients were compared with those for nine adult male controls (37.0 +/- 2.7 year). The GH response to hexarelin was negligible in patients with GHD compared to control subjects (CS) (peak: 1.9 +/- 0.9 vs. 45.7 +/- 3.6 mu g/l, P &lt; 0.001). Basal left ventricular ejection fraction (LVEF) in patients with GHD was lower than that in CS (50 +/- 1% vs. 63.2%, P &lt; 0.001). Hexarelin administration increased LVEF both in patients with GHD and in CS (peak: 57 +/- 2 vs. 70 +/- 2, respectively, P &lt; 0.05 vs. baseline) without changing catecholamine levels, mean blood pressure (MBP), or cardiac output in either group. In conclusion, the acute administration of hexarelin exerts a short-lasting positive inotropic effect in humans, probably GH-independent and mediated by specific myocardial receptors for GH secretagogues. (C) 1999 Elsevier Science B.V. All rights reserved.

1999 - Effect of melatonin on catecholamines: modulation by estrogens [Altro]
Zanni, Al; Cagnacci, Angelo; Del RIO, G; Veneri, Mg; Renzi, A; Volpe, Annibale
abstract

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1999 - GH/IGF-I axis in azoospermia in primary and secondary hypogonadism: a study before and during replacement therapy. [Articolo su rivista]
Carani, Cesare; Mantovani, R.; Procopio, M.; DEL RIO, G.; Rossetto, R.; Granata, A. R. M.
abstract

The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis was studied in 15 azoospermic patients and in 10 control men. Eight patients were affected by hypergonadotrophic hypogonadism and 7 by hypogonadotrophic hypogonadism. All were studied before and during replacement therapy with testosterone and gonadotrophin, respectively, using the alpha 2 adrenergic agonist, clonidine (clonidine test). The data demonstrate no differences in basal levels for IGF-I and for the GH response to clonidine in azoospermic patients, affected by primary and secondary hypogonadism, before and during replacement therapy when compared with control fertile men. In contrast to some studies which describe a reduced GH response in azoospermia and oligozoospermia, we conclude that basal serum levels of IGF-I and the GH response to clonidine are not impaired in azoospermic patients affected by primary hypogonadism before and after the restoration of normal androgenization, and in azoospermic patients affected by secondary hypogonadism, both before and after restoration of spermatogenesis.

1999 - Influence of melatonin on baseline and stimulated catecholamine levels in postmenopausal women prior and during estrogen replacement therapy [Altro]
Cagnacci, Angelo; Zanni, Al; Del Rio, G; Veneri, Mg; Arangino, S; Landi, S; Volpe, Annibale
abstract

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1999 - La terapia ormonale sostitutiva ripristina l' effetto della melatonina sui livelli basali e stimolati di catecolamine [Altro]
Zanni, A; Cagnacci, Angelo; Del Rio, G; Veneri, Mg; Volpe, Annibale
abstract

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1999 - Radionuclide angiocardiographic evaluation of the cardiovascular effects of recombinant human IGF-I in normal adults [Articolo su rivista]
Bisi, G; Podio, V; Valetto, Fr; Broglio, F; Bertuccio, G; DEL RIO, Graziano; Boghen, Mf; Berti, F; Muller, Ee; Ghigo, E.
abstract

Objective: IGF-I possesses specific myocardial receptors and is able to promote cardiac remodelling and even inotropic effects in both humans and other animals. In fact, reduced cardiac mass and performance are present in GH deficiency and these alterations are counteracted by recombinant human (rh) GH replacement, restoring IGF-I levels. Recently, the acute administration of 60 mu g/kg rhIGF-I has also been reported to be able to improve cardiac performance evaluated by echocardiography or impedance cardiography in normal subjects. The aim of our study was to verify the effects of a subcutaneous low dose of rhIGF-I (20 mu g/kg) on cardiac performance in humans. Methods: In six healthy male adults (mean +/- S.E.M.: 35.7 +/- 4.3 years of age), the effects of rhIGF-I on left ventricular function evaluated by radionuclide angiocardiography and on circulating IGF-I, GH, insulin, glucose and catecholamines levels were studied. Results: Administration of rhIGF-I increased circulating IGF-I (peak at +150 min vs baseline: 330.2 +/- 9.6 vs 199.7 +/- 8.7 mu g/l, P &lt; 0.03) to levels which persisted similarly up to +180 min. Neither GH nor catecholamine levels were modified by rhIGF-I administration, while insulin and glucose levels showed a slight but significant decrease. Basal left ventricular ejection fraction (61.8 +/- 2.0%) significantly increased at +180 min after rhIGF-I (65.3 +/- 2.7%, P &lt; 0.03). No change was recorded in mean blood pressure while a non-significant trend towards a reduction of heart rate was present by +120 min. Conclusions: These findings indicate that even subcutaneous administration of a low dose of rhIGF-I has acute inotropic effects as evaluated by radionuclide angiocardiography in healthy adults.

1999 - Regulation of ob gene expression: evidence for epinephrine-induced suppression in human obesity [Articolo su rivista]
Carulli, Lucia; Ferrari, S; Bertolini, M; Tagliafico, Enrico; DEL RIO, Graziano
abstract

Leptin acts as satiety factor and increases energy expenditure. Studies conducted on animals and in vitro on adipocytes culture have shown that infusion of catecholamines leads to a significant reduction of ob gene expression; it appears of interest to evaluate the in vivo effects of adrenergic activation on the expression of the ob gene in humans. We studied ob gene expression in adipose tissue samples from 13 obese subjects before and after epinephrine (25 ng/min x kg ideal body weight for 3 h) and 6 obese patients during saline infusion. Hormonal infusion led to a significant increase in epinephrine plasma levels (from 27 +/- 4 to 339 +/- 75 pg/mL; P < 0.001), plasma free fatty acids (from 0.73 +/- 0.05 to 0.98 +/- 0.07; P < 0.05), heart rate (13.5 +/- 3.1 beats/min; F = 2.9; P < 0.03), and systolic blood pressure (F = 2.7; P < 0.05), whereas diastolic blood pressure did not show significant variation. Plasma leptin levels decreased by the end of the infusion (from 63 +/- 13 to 49 +/- 11 ng/mL; P < 0.05), and ob messenger ribonucleic acid levels were significantly reduced (decrease amounting to 47 +/- 5% of basal values). Our study shows that adrenergic activation contributes to regulate ob messenger ribonucleic acid levels in humans. The interaction between epinephrine and leptin may operate during metabolic and psychological stress to regulate energy expenditure and food intake.

1998 - Acute infusion of naloxone, an opioid receptor antagonist, does not modify serum leptin concentrations in amenorrheic and healthy women [Articolo su rivista]
Genazzani, Alessandro; Menozzi, Renata; DEL RIO, Graziano; Luisi, Stefano; Petraglia, Felice; Genazzani, Andrea R.
abstract

Objective: To determine whether the opioidergic system is involved in the modulation of leptin secretion in healthy and amenorrheic subjects. Design: Prospective study. Setting: Department of Obstetrics and Gynecology, University of Modena, Modena, Italy. Patient(s): Healthy subjects (n = 8) and patients with hypothalamic amenorrhea (n = 17) or hyperandrogenism (n = 7) and low body mass index (BMI). Intervention(s): Acute infusion of naloxone (4-mg bolus) and blood sampling 15 minutes before infusion; at time of infusion; and 15, 30, 45, 60, 75, 90, and 120 minutes after infusion. Main Outcome Measure(s): Plasma leptin, LH, FSH, E2, and cortisol concentrations. Result(s): Plasma leptin concentrations were lower (P <.01) in both hypothalamic and hyperandrogenic amenorrheic subjects than in healthy controls. In all groups of subjects, no significant changes in leptin levels were observed after infusion of naloxone. A significant correlation was found between leptin concentrations and BMI when all subjects were considered together (P <.05) but was not found in the single groups. Conclusion(s): The present data do not support the hypothesis that opioidergic receptors are involved acutely in the modulation of leptin release in healthy and amenorrheic women.

1998 - Effects of galanin and the galanin receptor antagonist galantide on plasma catecholamine levels during a psychosocial stress stimulus in rats [Articolo su rivista]
G., Ceresini; A., Sgoifo; M., Freddi; E., Musso; DEL RIO, Graziano; S., Parmigiani; G., Valenti
abstract

The aim of this study was to investigate the role played by the neuropeptide galanin (GAL) in the regulation of sympathoadrenal function. We evaluated the effects of rat GAL (rGAL) and of the putative GAL receptor antagonist galantide (GLT) on epinephrine (E) and norepinephrine (NE) plasma levels in conscious freely moving male rats, during a psychosocial stress condition. Four groups of male rats were challenged by a stress stimulus, obtained by exposing the animals to a resident conspecific fighter (intruder model), following an intravenous injection with (1) rGAL + saline (SAL), (2) GLT + SAL, (3) rGAL + GLT, or (4) SAL + SAL. Plasma levels of both E and NE were also measured in an additional group of male rats not exposed to any stressor stimulus. The results (mean +/- SEM) showed that rats exposed to the stressor stimulus (intruder rats) exhibited a significant increase above baseline in circulating levels of both E (peak values of 834.13 +/- 115.13 pmol/l vs. basal values of 309.31 +/- 32.93 pmol/l; p &lt; 0.01) and NE (peak values of 5,299.03 +/- 450.62 pmol/l vs. basal values of 2,798.24 +/- 311.56 pmol/l; p &lt; 0.01) in comparison to control, non-stressed rats. The comparison of the areas under the curve response (AUC) among treatments in the intruder rats revealed that rGAL + SAL injections resulted in a further increase in E levels when compared to SAL + SAL treatment (AUC values: 8.26 +/- 0.64 vs. 25.38 +/- 5.52 nmol/l/20 min in SAL + SAL vs. rGAL + SAL treatment, respectively; p &lt; 0.02). No significant changes in stress-induced E plasma levels were found following GLT + SAL treatment in comparison to SAL + SAL injections. When the intruder rats were submitted to rGAL + GLT injections, the increments in E levels were found to be higher than those observed following SAL + SAL treatment (AUC values: 8.26 +/- 0.64 vs. 36.00 +/- 13.76 nmol/l/20 min in SAL + SAL vs. rGAL + GLT treatment, p &lt; 0.03); however, the values were not significantly different from those observed in rGAL + SAL-injected rats. No significant changes in stress-induced NE levels were found in either treatment group when compared to SAL + SAL-injected intruder rats. The results of this study demonstrate that rGAL administration leads to an increase in the E response to the stress stimulus without any effect on NE response. Galantide does not affect either the physiological stress-induced elevation of plasma catecholamines or the effects of rGAL on E plasma levels in response to stress. Therefore, GLT does not appear to behave as a GAL receptor antagonist in the regulation of sympathoadrenal function in rats.

1998 - Prolonged administration of transdermal estradiol decreases catecholamine secretion in postmenopausal women [Altro]
Cagnacci, Angelo; Del Rio, G; Zanni, Al; Veneri, Mg; Malmusi, S; Landi, S; Volpe, Annibale
abstract

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1997 - Alpha-2 adrenergic activity in perimenopausal women [Articolo su rivista]
DEL RIO, Graziano; Menozzi, R; Della Casa, L; Venneri, Mg; Zizzo, G; Marrama, P; Velardo, Antonino
abstract

Lipid alterations and increased blood pressure may occur during perimenopause. No data are available in perimenopausal women on the alpha-2 adrenergic activity which affects norepinephrine secretion. We studied cardiovascular and catecholamine responses to clonidine (300 mg per os) in a group of 15 perimenopausal women (PeriMW) and in a control group of 13 premenopausal women (PreMW). Nine of the perimenopausal women were also studied after 4-month percutaneous estrogen replacement therapy (PeriMWE). Systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), plasma norepinephrine (NE) and epinephrine (E) were evaluated before and at 120 min, 130 min, 140 min after clonidine administration. Basal values of SBP, DBP and HR were not different (F=0.7, p=NS; F=0.2, p=NS and F=0.1, p=NS respectively) between PeriMW both before and after therapy and PreMW, Resting levels of E were similar in PreMW and in PeriMW before and during estrogen therapy (F=0.8, p=NS); PeriMW showed higher basal NE levels both before and during estrogen therapy than PreMW (F=12; p&lt;0.001). Clonidine administration decreased SBP, DBP and NE levels in PreMW, in PeriMW and in PeriMWE without any difference between the groups (F=1.2, p=NS; F=0.5, p=NS and F=1.3, P=NS respectively). HR decreased significantly after clonidine in PreMW (F=5.4, p&lt;0.03) but not in PeriMW before (F=1.0, p=NS) and during estrogen therapy (F=0.5, p=NS). Clonidine did not affect plasma E in the three groups studied (F=2.8, p=NS; F=2.2, P=NS and F=0.1, p=NS). The present study demonstrates that increased basal plasma NE levels are present in PeriMW. The cardiovascular and catecholamine response to clonidine in PeriMW both before and during estrogen therapy are similar to those observed in PreMW, suggesting a normal inhibitory alpha-2 receptor pathway.

1996 - The effects of clonidine on blood pressure, catecholamine and growth hormone release in hypogonadal men is preserved and not influenced by testosterone replacement therapy [Articolo su rivista]
G., Delrio; Carani, Cesare; Velardo, Antonino; M., Procopio; G., Zizzo; P., Savio; R., Mantovani; P., Marrama; E., Ghigo
abstract

It has been demonstrated that castration impairs the hypotensive effect of clonidine in rat as well as its OH-releasing activity while testosterone replacement restores to normal the effects of alpha-2 adrenoceptor activation. Thus, these data point to main role of the gonadal steroid testosterone in modulating the effects of alpha-2 adrenergic activation on blood pressure, catecholamine and GH release in animal. Aim of the present study was to verify the activity of clonidine on blood pressure, catecholamine and GH release in human male hypogonadism before and after testosterone replacement. To this goal, 14 hypogonadal men (HP, age 33.8+/-2.9 yr; BMI<25 kg/m(2); 8 with hypergonadotropic and 6 with hypogonadotropic hypogonadism) received clonidine administration (CLON, 300 mu g po at 0 min) before and after 3 months of testosterone replacement (testosterone propionate depot, 250 mg i.m. every 21 days). Ten normal adult volunteers (NS, age 31.5+/-1.9 yr; BMI<25 kg/m(2)) were studied as control group. in all subjects, before and after clonidine administration, systolic and diastolic blood pressure (SEP and DBP), pulse rate (PR), norepinephrine (NE), epinephrine (Ef and GH levels were recorded. In HP basal testosterone levels were lower than those in NS (1.25+/-0.3 vs 7.34+/-1.5 ng/ml, p<0.05) and were restored to normal by hormonal replacement (6.91+/-1.3 ng/ml) In HP, both SSP and DBP as well as PR were normal in basal conditions and were not modified by testosterone replacement. Both before and during testosterone CLON lowered SEP, DBP and PR in HP to the same extent observed in NS, In HP, basal NE levels were lower than those in NS (0.85+/-0.15 vs 1.28+/-0.19 nmol/l, p<0.05) and were restored to normal during testosterone replacement (1.25+/-0.13 nmol/l). On the other hand, basal E levels in HP were similar to those in NS (179+/-42 vs 197+/-38 pmol/l) and were not modified by testosterone therapy (167+/-28 pmol/l). in HP, both before and during testosterone replacement, CLON reduced NE (0.44+/-0.10 and 0.58+/-0.07 nmol/l) levels to the same levels recorded in NS (0.68+/-0.08 nmol/l). Basal GH and IGF-I levels in HP (1.15+/-0.5 and 234+/-42 mu g/l, respectively) were similar to those in NS (1.18+/-0.4 and 221+/-38 mu g/l, respectively) and were not modified by testosterone (1.35+/-0.6 and 256+/-32 mu g/l, respectively). CLON administration induced a clear GH response in HP (F=37; p<0.001) which overlapped with that recorded in NS and was not modified by testosterone (F=1.7; P=NS). Our present findings demonstrate that, differently from in animal, in man testosterone has no role in modulating the effects of alpha-2 adrenergic activation by clonidine on blood pressure, catecholamine and GH release, On the other hand, our data suggest the existence in male hypogonadism of a reduced basal noradrenergic activity which is restored by testosterone replacement.

1995 - Cardiovascular and catecholamine response to clonidine in obese subjects [Articolo su rivista]
G., Zizzo; DEL RIO, Graziano; Me, Bonati; Ia, Macdonald; Velardo, Antonino
abstract

OBJECTIVE: To investigate central alpha-2 adrenergic activity, one of the main inhibitory factors affecting norepinephrine secretion, in human obesity. DESIGN: Cardiovascular and catecholamine responses to clonidine (300 mu g per os) were evaluated in a group of obese subjects. SUBJECTS: 10 obese men (OM) and 14 obese women (OW). MEASUREMENTS: Mean arterial pressure, pulse rate, plasma norepinephrine (NE) and epinephrine (E) before and 120', 130', 140' after clonidine (CL) administration. RESULTS: The mean arterial pressure decreased after CL administration in obese patients (from 92 +/- 12 to 79 +/- 2 mmHg; P &lt; 0.001) with no significant differences between OM and OW. The values of pulse rate were reduced in obese patients after clonidine (60 +/- 1 b/min vs 65 +/- 1 b/min before clonidine; P &lt; 0.01) with no differences between OM and OW. Plasma E was not affected by the administration of clonidine and no sex related differences were found in the basal (OM: 0.23 +/- 0.03 vs OW: 0.15 +/- 0.03 nmol/L; P = NS) and in the post-CL E levels (OM: 0.22 +/- 0.02 vs OW: 0.14 +/- 0.03 nmol/L; P = NS). Basal plasma NE values were not different between OM (1.32 +/- 0.15 nmol/L) and OW (1.03 +/- 0.11 nmol/L; P = NS). Plasma NE decreased after CL in obese patients (from 1.20 +/- 0.10 to 0.59 +/- 0.08 nmol/L; P &lt; 0.001) and a significant difference was found in the post-CL values between OM and OW (0.74 +/- 0.11 vs 0.40 +/- 0.06 nmol/L respectively; P &lt; 0.01). The decrease in plasma NE was strongly correlated with the basal value of NE (r = 0.70; P &lt; 0.001). The sex-related differences in plasma NE responses to clonidine in obese subjects did not differ with those previously observed in control subjects (P = NS). CONCLUSION: The cardiovascular and catecholamine response to CL in obese patients were similar to that previously observed in normal subjects, indicating a normal alpha-a adrenergic activity. The sex related difference in the NE response to CL, previously reported in normal subjects, was maintained in obese patients.

1995 - Effect of testosterone replacement therapy on the somatotrope responsiveness to GHRH alone or combined with pyridostigmine and on sympathoadrenal activity in patients with hypogonadism [Articolo su rivista]
G., Del Rio; Carani, Cesare; Velardo, Antonino; G., Zizzo; M., Procopio; F., Coletta; P., Marrama; E., Ghigo
abstract

There is evidence suggesting that androgens influence GH secretion in man. Our aim was to verify whether the GH releasable pool is preserved and influenced by testosterone replacement in male hypogonadism. To this goal, in eight male hypogonadal patients (HP, age 32.2+/-5.0 yr; Body Mass Index 23.9+/-1.1 kg/m(2)) before and after 3 months testosterone therapy, we studied the GH response to GHRH (1 mu/kg iv) alone and combined with pyridostigmine (PD, 120 mg po), a cholinesterase inhibitor which likely inhibits hypothalamic somatostatin release allowing exploration of the maximal somatotrope secretory pool. Sixteen normal subjects (NS, age 30.1+/-3.5 yr; Body Mass Index 22.5+/-1.8 kg/m(2)) were studied as controls. The GH response to GHRH in HP was similar to that in NS (AUG, mean+/-SE: 1238+/-362 vs 1018+/-182 mu g/L/h). PD potentiated to the same extent the GH response to GHRH in both groups (2092+/-807 and 2840+/-356 mu g/L/h). After three month testosterone therapy, in HP the GH responses to GHRH alone (1352+/-612 mu g/L/h) and combined with PD (1948+/-616 mu g/L/h) were unchanged. Also IGF-I levels in HP were similar to those in NS (222+/-42 vs 210.6+/-55.8 mu g/L) and were unchanged during testosterone replacement (280+/-31 mu g/L). As androgens have been reported to modulate sympathoadrenal activity in the rat, both before and during testosterone replacement, we also measured plasma catecholamine levels, Basal NE (p< 0.05) but not E levels were lower in HP than in NS; testosterone restored basal NE levels to normal without affecting basal E. Delta absolute increase of NE and E (p<0.05 and 0.01 vs baseline, respectively) after PD in HP were similar to those in NS and were unchanged during testosterone replacement. In conclusion, these results demonstrate that the GH releasable pool is preserved in male hypogonadism, As in this condition a reduction of spontaneous GH secretion has been reported, it could be due to neurosecretory dysfunction but not to pituitary impairment, Subtle alterations of sympathoadrenal activity seem to be present in male hypogonadism and reversed by testosterone replacement.

1992 - Circadian rhythm of plasma testosterone in men with idiopathic hypogonatropic hypogonadism before and during pulsatile administration of gonadotropin-releasing hormone. [Articolo su rivista]
Simoni, Manuela; Montanini, V; FAUSTINI FUSTINI, M; DEL RIO, G; Cioni, K; Marrama, P.
abstract

OBJECTIVE: The aim was to investigate whether a pulsatile discharge of LH from the pituitary is necessary to achieve the circadian secretion of testosterone. DESIGN: The daily rhythm of the androgen has been studied in patients with idiopathic hypogonadotrophic hypogonadism (IHH) both in the absence of therapy and during pulsatile administration of gonadotrophin releasing hormone (GnRH). PATIENTS: Six patients with IHH and ten normal subjects were analysed. Blood sampling was performed at 2-hourly intervals, for 24 hours. The IHH patients then received synthetic GnRH i.v. at the rate of one pulse every 2 hours (10 micrograms/pulse). On day 11 of treatment, blood samples were taken for the rhythm analysis every 2 hours, for 24 hours. MEASUREMENTS: Plasma testosterone and LH were measured in the individual samples by radioimmunoassay. Evaluation of the rhythm was performed by cosinor analysis. RESULTS: A significant circadian rhythm of plasma testosterone was statistically validated in the normal subjects, whereas no rhythm was detected in the IHH patients in the absence of therapy. On day 11 of GnRH pulsatile administration the IHH patients showed normal testosterone levels and a statistically significant circadian rhythm of the androgen was evident, with acrophase between 0700 and 0800 h. Moreover, the amplitude, acrophase and mesor of testosterone rhythm in IHH patients in the course of treatment were statistically indistinguishable from the corresponding values in the normal subjects. Plasma LH did not show statistically significant circadian variations, either in the control group or in the IHH patients before or during therapy. CONCLUSIONS: We conclude that a physiological circadian rhythm of plasma testosterone can be obtained, in IHH men, by treatment with GnRH. Since the pulsatile administration of exogenous GnRH at constant doses induced a circadian rhythm in testosterone and no daily variations in LH were evident, we suggest that, although a pulsatile secretion of LH is probably necessary for the synchronization of the circadian rhythm with acrophase in the morning, the testosterone variations might be the results of a local testicular modulation of LH action.

1992 - Sexual dimorphism of the autonomic nervous system response to weight loss in obese patients [Articolo su rivista]
G., Delrio; Carani, Cesare; M., Bonati; P., Marrama; L., Dellacasa
abstract

The sex-related response of the sympathoadrenal system to very low calorie diet (VLCD) with sodium restriction has been studied in a group of 16 obese subjects (8 men; 8 women). Once in sodium balance obese men were different from women in respect to initial body weight, mean daily 4 h urinary excretion of epinephrine (E) and norepinephrine (NE) measured for 48 h. After 20 days of VLCD the weight loss was higher in men than women (P < 0.01), E excretion increased in men more than in women (P < 0.01), and was correlated with weight decrement (r = 0.78; P < 0.01). NE excretion decreased in a similar way in both sexes. The present findings demonstrate sexual dimorphism in catecholamine excretion during VLCD and provide further evidence of the relative autonomy of adrenomedullary secretion from sympathetic nervous system activity.

1992 - Testosterone and erectile function nocturnal penile tumescence and rigidity, and erectile response to visual erotic stimuli in hypogonadal and eugonadal men. [Articolo su rivista]
Carani, Cesare; Bancroft, J.; Granata, A. R. M.; DEL RIO, G.; Marrama, P.
abstract

Further evidence that nocturnal erections are androgen-dependent and erectile responses to visual erotic stimuli are androgen-independent is presented from six men with secondary hypogonadism and six eugonadal controls. Erections during sleep were substantially less in the hypogonadal men, in terms of both tumescence and rigidity. In response to visual erotic stimuli, the percentage increase in circumference over baseline and the increase in rigidity were similar for the two groups.

1990 - Chronobiology of cathecolamine excretion in normal and diabetic men [Articolo su rivista]
G., Delrio; Carani, Cesare; A., Baldini; P., Marrama; L., Dellacasa
abstract

not available

1990 - The endocrine effects of visual erotic stimuli in normal men. [Articolo su rivista]
Carani, Cesare; J., Bancroft; G., Del Rio; A. R. M., Granata; Facchinetti, Fabio; P., Marrama
abstract

not available