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Dive into the research topics where Barbara Lucatello is active.

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Featured researches published by Barbara Lucatello.


Hypertension | 2014

Somatic ATP1A1, ATP2B3, and KCNJ5 Mutations in Aldosterone-Producing Adenomas

Tracy A. Williams; Silvia Monticone; Vivien Rodacker Schack; Julia Stindl; Jacopo Burrello; Fabrizio Buffolo; Laura Annaratone; Isabella Castellano; Felix Beuschlein; Martin Reincke; Barbara Lucatello; Vanessa Ronconi; Francesco Fallo; Giampaolo Bernini; Mauro Maccario; Gilberta Giacchetti; Franco Veglio; Richard Warth; Bente Vilsen; Paolo Mulatero

Aldosterone-producing adenomas (APAs) cause a sporadic form of primary aldosteronism and somatic mutations in the KCNJ5 gene, which encodes the G-protein–activated inward rectifier K+ channel 4, GIRK4, account for ≈40% of APAs. Additional somatic APA mutations were identified recently in 2 other genes, ATP1A1 and ATP2B3, encoding Na+/K+-ATPase 1 and Ca2+-ATPase 3, respectively, at a combined prevalence of 6.8%. We have screened 112 APAs for mutations in known hotspots for genetic alterations associated with primary aldosteronism. Somatic mutations in ATP1A1, ATP2B3, and KCNJ5 were present in 6.3%, 0.9%, and 39.3% of APAs, respectively, and included 2 novel mutations (Na+/K+-ATPase p.Gly99Arg and GIRK4 p.Trp126Arg). CYP11B2 gene expression was higher in APAs harboring ATP1A1 and ATP2B3 mutations compared with those without these or KCNJ5 mutations. Overexpression of Na+/K+-ATPase p.Gly99Arg and GIRK4 p.Trp126Arg in HAC15 adrenal cells resulted in upregulation of CYP11B2 gene expression and its transcriptional regulator NR4A2. Structural modeling of the Na+/K+-ATPase showed that the Gly99Arg substitution most likely interferes with the gateway to the ion binding pocket. In vitro functional assays demonstrated that Gly99Arg displays severely impaired ATPase activity, a reduced apparent affinity for Na+ activation of phosphorylation and K+ inhibition of phosphorylation that indicate decreased Na+ and K+ binding, respectively. Moreover, whole cell patch-clamp studies established that overexpression of Na+/K+-ATPase Gly99Arg causes membrane voltage depolarization. In conclusion, somatic mutations are common in APAs that result in an increase in CYP11B2 gene expression and may account for the dysregulated aldosterone production in a subset of patients with sporadic primary aldosteronism.


European Journal of Endocrinology | 2007

Endocrine and metabolic responses to extreme altitude and physical exercise in climbers

Andrea Benso; Fabio Broglio; Gianluca Aimaretti; Barbara Lucatello; Fabio Lanfranco; Ezio Ghigo; S. Grottoli

CONTEXT Chronic hypoxia induces complex metabolic and endocrine adaptations. High-altitude (HA) exposure is a physiological model of hypoxia. OBJECTIVE To further investigate the endocrine and metabolic responses to extreme HA. METHODS We studied nine male elite climbers at sea level and at 5200 m after climbing Mt. Everest. RESULTS After 7 weeks at HA, body weight was reduced (P<0.05); regarding endocrine variables we observed: a) an increase of 2-h mean GH concentration (P<0.05) as well as of total IGF-I and IGF binding protein-3 levels (P<0.05 for both); b) a prolactin increase (P<0.05) coupled with testosterone decrease (P<0.01) and progesterone increase (P<0.05) without any change in estradiol levels: c) no change in cortisol, ACTH, and dehydroepiandrosterone sulfate (DHEAS) levels; d) an increase in free thyroxine (P<0.05) and free tri-iodothyronine (T(3)) decrease (P<0.05) but no change in TSH levels; e) a plasma glucose decrease (P<0.05) without any change in insulin levels; f) an increase in mean free fatty acid levels (P<0.05); g) despite body weight loss, leptin levels showed non-significant trend toward decrease, while ghrelin levels did not change at all. CONCLUSIONS The results of the present study in a unique experimental human model of maximal exposure to altitude and physical exercise demonstrate that extreme HA and strenuous physical exercise are coupled with specific endocrine adaptations. These include increased activity of the GH/IGF-I axis and a low T(3) syndrome but no change in ghrelin and leptin that was expected taking into account body weight decrease. These findings would contribute to better understanding human endocrine and metabolic physiology in hypoxic conditions.


Molecular and Cellular Endocrinology | 2015

Immunohistochemical, genetic and clinical characterization of sporadic aldosterone-producing adenomas.

Silvia Monticone; Isabella Castellano; Karine Versace; Barbara Lucatello; Franco Veglio; Celso E. Gomez-Sanchez; Tracy A. Williams; Paolo Mulatero

Adrenal glands removed for unilateral primary aldosteronism (PA) display marked histological heterogeneity. Recently reported somatic mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D can partially account for these differences. In this study we aimed at combining phenotypic and genotypic characteristics, integrating genetic and immunohistochemistry correlates in sporadic PA. Seventy-one adrenal glands have been included in the study and analyzed for mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. Histological examination and immunohistochemical staining for CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) were performed on aldosterone-producing adenomas (APAs) and adjacent adrenal cortex. In our cohort, the final histopathological diagnosis was multinodular hyperplasia in 22.5% of the patients and single nodule in 77.5%. Forty-five percent of the removed adrenals displayed extra-APA CYP11B2-positive cell nests (B2-CN). Among adrenal vein sampling parameters the suppression of contralateral adrenal was more frequent and the lateralization index was higher in the subgroup of patients without extra-APA B2-CN compared to the subgroup with extra-APA B2-CN. KCNJ5-mutated APAs were composed mainly of zona fasciculata-like cells with high expression of CYP11B1, while ATP1A1, ATP2B3 and CACNA1D-mutated APAs presented more frequently a zona-glomerulosa-like phenotype with high expression of CYP11B2. We observed a significant inverse correlation between CYP11B2 expression and the size of the nodules and, if CYP11B2 expression was corrected for tumor volume, a significant correlation with plasma aldosterone and aldosterone to renin ratio. Our findings indicate that combination of genotyping and immunohistochemistry improves the final histopathological diagnosis between single nodule and multinodular hyperplasia of the assessed adrenals.


The Journal of Clinical Endocrinology and Metabolism | 2014

Aldosterone Suppression on Contralateral Adrenal During Adrenal Vein Sampling Does Not Predict Blood Pressure Response After Adrenalectomy

Silvia Monticone; Fumitoshi Satoh; Andrea Viola; Evelyn Fischer; Oliver Vonend; Giampaolo Bernini; Barbara Lucatello; Marcus Quinkler; Vanessa Ronconi; Ryo Morimoto; Masataka Kudo; Christoph Degenhart; Xing Gao; Davide Carrara; Holger S. Willenberg; Denis Rossato; Giulio Mengozzi; Anna Riester; Enrico Paci; Yoshitsugu Iwakura; Jacopo Burrello; Mauro Maccario; Gilberta Giacchetti; Franco Veglio; Sadayoshi Ito; Martin Reincke; Paolo Mulatero

CONTEXT Adrenal vein sampling (AVS) is the only reliable means to distinguish between aldosterone-producing adenoma and bilateral adrenal hyperplasia, the two most common subtypes of primary aldosteronism (PA). AVS protocols are not standardized and vary widely between centers. OBJECTIVE The objective of the study was to retrospectively investigate whether the presence of contralateral adrenal (CL) suppression of aldosterone secretion was associated with improved postoperative outcomes in patients who underwent unilateral adrenalectomy for PA. SETTING The study was carried out in eight different referral centers in Italy, Germany, and Japan. PATIENTS From 585 consecutive AVS in patients with confirmed PA, 234 procedures met the inclusion criteria and were used for the subsequent analyses. RESULTS Overall, 82% of patients displayed contralateral suppression. This percentage was significantly higher in ACTH stimulated compared with basal procedures (90% vs 77%). The CL ratio was inversely correlated with the aldosterone level at diagnosis and, among AVS parameters, with the lateralization index (P = .02 and P = .01, respectively). The absence of contralateral suppression was not associated with a lower rate of response to adrenalectomy in terms of both clinical and biochemical parameters, and patients with CL suppression underwent a significantly larger reduction in the aldosterone levels after adrenalectomy. CONCLUSIONS For patients with lateralizing indices of greater than 4 (which comprised the great majority of subjects in this study), CL suppression should not be required to refer patients to adrenalectomy because it is not associated with a larger blood pressure reduction after surgery and might exclude patients from curative surgery.


European Journal of Endocrinology | 2013

Long-term re-evaluation of primary aldosteronism after medical treatment reveals high proportion of normal mineralocorticoid secretion.

Barbara Lucatello; Andrea Benso; Isabella Tabaro; Elena Capello; Mirko Parasiliti Caprino; Lisa Marafetti; Denis Rossato; S. E. Oleandri; Ezio Ghigo; Mauro Maccario

OBJECTIVE In most cases of primary aldosteronism (PA), An adrenal aldosterone-secreting tumor cannot be reasonably proven, so these patients undergo medical treatment. Controversial data exist about the evolution of PA after medical therapy: long-term treatment with mineralocorticoid antagonists has been reported to normalize aldosterone levels but other authors failed to find remission of mineralocorticoid hypersecretion. Thus, we planned to retest aldosterone secretion in patients with medically treated PA diagnosed at least 3 years before. DESIGN Retrospective, cross-sectional study. METHODS The same workup for PA as at diagnosis (basal aldosterone to renin activity ratio (ARR) and aldosterone suppression test) was performed after stopping interfering drugs and low-salt diet, in 34 subjects with PA diagnosed between 3 and 15 years earlier, by case finding from subgroups of hypertensive patients at high risk for PA. Criteria for persistence of PA were the same as at diagnosis (ARR (pg/ml per ng per ml per h) >400, aldosterone >150 pg/ml basally, and >100 pg/ml after saline infusion) or less restrictive. RESULTS PA was not confirmed in 26 (76%) of the patients and also not in 20 (59%) using the least restrictive criteria suggested by international guidelines. Unconfirmed PA was positively associated with female sex, higher potassium levels, longer duration of hypertension, and follow-up, but not with adrenal mass, aldosterone levels at diagnosis, and treatment with mineralocorticoid antagonists. CONCLUSIONS This study suggests that mineralocorticoid hyperfunction in patients with PA after medical treatment may decline spontaneously. Higher potassium concentration and duration of treatment seem to increase the probability of this event.


Journal of Endocrinological Investigation | 2010

The metabolic response to the activation of the β- adrenergic receptor by salbutamol is amplified by acylated ghrelin

D. H. St-Pierre; Andrea Benso; Elena Gramaglia; Flavia Prodam; Barbara Lucatello; V. Ramella-Gigliardi; Ilaria Olivetti; M. Tomelini; Fabio Broglio

Background: It is well recognized that β-adrenergic receptors mediate important endocrine and metabolic actions. In fact, β-adrenergic receptor activation negatively influences GH secretion while exerting relevant metabolic actions such as the stimulation of insulin secretion, glycogenosis, and lipolysis. Aim: We have already shown that the activation of the GH secretagogue receptor (GHS-R)-1a by acylated ghrelin (AG) counteracts the inhibitory effect of salbutamol (SALB), a β2-adrenergic agonist, on GH release. The aim of the present study in humans was to clarify whether the metabolic response to SALB is affected by the infusion of AG, also known to exert significant metabolic actions. Methods: Six healthy young male volunteers underwent the following testing sessions in random order at least 5 days apart: a) SALB (0.06 μg/kg/min iv from 0 to 60 min) alone; b) SALB in combination with AG (1.0 μg/kg/min iv from −60 to 60 min); c) isotonic saline. Insulin, glucose, and free fatty acids (FFA) levels were evaluated every 15 min. Results: As expected, with respect to saline, SALB administration tended to increase both insulin secretion [Δ area under the curve (ΔAUC): 0.16±0.09 vs 0.003±0.077 × 103 μU/ml/min; p>0.05] and FFA levels (ΔAUC: 8.0±7.3 vs ∼-4.0±4.0 mEq/l/min; p>0.05), while glucose levels did not change. The metabolic response to SALB was significantly modified under the exposure of AG. In fact, under AG infusion, SALB elicited a more marked increase of FFA (ΔAUC: 22.3±3.2 vs 8.0±7.3 mEq/l/min; p<0.05) as well as a slight elevation in insulin (ΔAUC: 0.37±0.11 vs 0.16±0.09 × 103 μU/ml/min; p>0.05). Under AG, the baseline glucose levels were more elevated but, again, in combination with AG, SALB did not significantly modify glucose levels. Conclusions: β-adrenergic receptors and AG are likely to interact at the metabolic level. In humans, the lypolitic response to a β2-adrenergic agonist such as SALB is amplified by AG. Meanwhile, during the co-treatment, the marginal insulinotropic effect was not associated with an increase in glycemia.


Clinical Genitourinary Cancer | 2017

Radiofrequency Ablation for Renal Cancer in Von Hippel–Lindau Syndrome Patients: A Prospective Cohort Analysis

Marco Allasia; Francesco Soria; Antonino Battaglia; Carlo Gazzera; Marco Calandri; Mirko Parasiliti Caprino; Barbara Lucatello; Andrea Velrti; Mario Maccario; Barbara Pasini; A. Bosio; Paolo Gontero; P. Destefanis

Introduction Management of renal‐cell carcinoma (RCC) in patients with Von Hippel–Lindau syndrome (VHL) represents a clinical dilemma: the oncologic outcomes must be weighed against preservation of renal function. Radiofrequency ablation (RFA) is currently used in selected cases for treatment of small‐size RCC. The aim of this study was to evaluate the safety, complications, and functional and oncologic outcomes of RFA in the treatment of RCC in VHL patients. Patients and Methods RCCs were treated with ultrasound‐guided RFA or with laparoscopic RFA. Clinical and radiologic response, disease recurrence, and survival outcomes were evaluated during follow‐up. Early and late complications were recorded and graded. Results Nine RCC patients underwent RFA. The median number of RCCs per patient was 3 (interquartile range, 2‐4). Among these 9 patients, a total of 20 RCCs were treated by RFA (19 ultrasound‐guided RFA and 1 laparoscopic procedure). Median RCC size was 2.5 cm (interquartile range, 2.0‐3.0). RFA did not impair renal function (P = .35). In 2 cases disease persisted, and in 1 case disease recurred after 18 months. These patients were retreated with ultrasound‐guided RFA with complete response and no renal function impairment. RFA treatment was overall well tolerated and safe. No complications were recorded. Postoperative stay was no longer than 1 day. Conclusion RCC occurred in about two‐thirds of VHL patients, who had young age at presentation; it was frequently multifocal and recurrent. The use of RFA, with extended indications, could represent a tailored treatment for VHL patients, reducing the risk of renal failure and resulting in satisfying oncologic results. Micro‐Abstract Management of renal‐cell carcinoma (RCC) in Von Hippel–Lindau syndrome (VHL) patients represents a clinical challenge. Radiofrequency ablation (RFA) is currently used in selected cases for treatment of small‐size RCC. The aim of this study was to evaluate the safety and complication rate of RFA in treating RCC in VHL patients. The treatment did not impair renal function and resulted in complete oncologic control.


Endocrine | 2016

Evolution of computed tomography-detectable adrenal nodules in patients with bilateral primary aldosteronism

Paolo Mulatero; Jacopo Burrello; Barbara Lucatello; Gilberta Giacchetti; Marialberta Battocchio; Francesco Fallo

Computed tomography (CT) appearance of adrenals in primary aldosteronism (PA) ranges from normal to bilateral diffuse enlargement or nodular glands. Idiopathic hyperaldosteronism (IHA) due to bilateral autonomous production of aldosterone (bilateral PA) is the most common subtype of PA, accounting for 50–70 % of PA patients [1, 2]. Regardless of adrenal image findings, IHA is diagnosed by adrenal venous sampling (AVS) in PA patients who do not show lateralization of aldosterone secretion [3], and is treated by long-term medical therapy using mineralocorticoid receptor antagonists. The other common PA subtypes, aldosterone-producing adenoma (APA) and unilateral adrenal hyperplasia, display lateralization of aldosterone secretion at AVS and are treated by unilateral adrenalectomy. Natural course of adrenal mass lesions in IHA patients has not yet been fully clarified. The aim of our study was to assess the over time evolution of CTdetectable adrenal nodule(s) in bilateral PA. Materials and methods


Biomarkers | 2016

Beta-2-glycoprotein-1 and alpha-1-antitrypsin as urinary markers of renal cancer in von Hippel–Lindau patients

Giorgia Mandili; Agata Notarpietro; Amina Khadjavi; Marco Allasia; Antonino Battaglia; Barbara Lucatello; Bruno Frea; Francesco Michelangelo Turrini; Francesco Novelli; Giuliana Giribaldi; P. Destefanis

Abstract Context: Von Hippel–Lindau disease (VHLD) is a rare inherited neoplastic syndrome. Among all the VHLD-associated tumors, clear cell renal cell carcinoma (ccRCC) is the major cause of death. Objective: The aim of this paper is the discovery of new non-invasive biomarker for the monitoring of VHLD patients. Materials and methods: We compared the urinary proteome of VHLD patients, ccRCC patients and healthy volunteers. Results: Among all differentially expressed proteins, alpha-1-antitrypsin (A1AT) and APOH (beta-2-glycoprotein-1) are strongly over-abundant only in the urine of VHLD patients with a history of ccRCC. Discussion and conclusion: A1AT and APOH could be promising non-invasive biomarkers.


Archive | 2006

Body Weight Regulation and Hypothalamic Neuropeptides

Flavia Prodam; Elisa Me; Fabrizio Riganti; Maria Angela Seardo; Barbara Lucatello; Mario Maccario; Ezio Ghigo; Fabio Broglio

The epidemic increasing incidence and prevalence of obesity and diabetes mellitus have underlined the necessity of understanding the regulation and control of appetite and energy metabolism.

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