Sant'Ambrogio di Torino, Italy
Sant'Ambrogio di Torino, Italy

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Settanni F.,Diabetology and Metabolism | Trovato L.,Diabetology and Metabolism | Alloatti G.,University of Turin | Ghigo E.,Diabetology and Metabolism | And 2 more authors.
Endocrinology | Year: 2013

GHRH stimulates GH synthesis and release from the pituitary and exerts direct effects in extrapituitary tissues. We have previously shown that pretreatment with GHRH reduces cardiomyocyte apoptosis and improves heart function in isolated rat hearts subjected to ischemia/reperfusion (I/R). Here, we determined whether GHRH given at reperfusion reduces myocardial reperfusion injury and investigated the molecular mechanisms involved in GHRH effects. Isolated rat hearts subjected to I/R were treated at the onset of reperfusion with: 1) GHRH; 2) GHRH+GHRH antagonist JV-1-36; 3) GHRH+mitochondrial ATP-dependent potassium channel inhibitor 5-hydroxydecanoate; 4) GHRH+mitochondrial permeability transition pore opener atractyloside; 5) GHRH+ phosphoinositide 3-kinase/Akt inhibitor Wortmannin (WM); and 6) GHRH+signal transducer and activator of transcription-3 inhibitor tyrphostin-AG490 (AG490). GHRH reduced infarct size at the end of reperfusion and reverted contractility dysfunction in I/R hearts. These effects were inhibited by either JV-1-36, 5-hydroxydecanoate, atractylosid, WM, or AG490. Western blot analysis on left ventricles showed GHRH-induced phosphorylation of either the reperfusion injury salvage kinases (RISK), phosphoinositide 3-kinase/Akt, ERK1/2, and glycogen synthase kinase-3β or signal transducer and activator of transcription-3, as part of the survivor activating factor enhancement (SAFE) pathway. GHRH-induced activation of RISK and SAFE pathways was blocked by JV-1-36, WM, and AG490. Furthermore, GHRH increased the phosphorylation of endothelial nitric oxide synthase and AMP-activated protein kinase and preserved postischemic nicotinamide adenine dinucleotide (NAD+) levels. These results suggest that GHRH protects the heart from I/R injury through receptor-mediated mechanisms, leading to activation of RISK and SAFE pathways, which converge on mitochondria and possibly on AMP-activated protein kinase. Copyright © 2013 by The Endocrine Society.


PubMed | University of Padua, University of Bari, Unit of Diabetology, The Second University of Naples and 7 more.
Type: Comparative Study | Journal: Acta diabetologica | Year: 2016

The aim of the study was to evaluate and compare continuous subcutaneous insulin infusion (CSII) use in pediatric and adult age groups.Data were collected with a questionnaire sent by e-mail to CSII-experienced Diabetes Centers. The questionnaire assessed: (1) number of CSII-treated patients; (2) patient demographic data and characteristics; (3) structure and organization of Diabetes Centers providing CSII therapy; (4) pump characteristics (conventional pump, sensor-augmented pump); and (5) CSII dropouts.A total of 217 out of 1093 Italian centers participated: 51 pediatric (23.5%) and 166 (76.5%) adult centers (AP). Compared to a survey performed in 2005, there was a significant increase in the number of pediatric units when compared to adult units (112 vs 37%, respectively, p<0.05). Pediatric age is characterized by a greater concern for quality of life and injections, and a higher dropout rate (10.6 vs 8.9%) mainly related to pump wearability and site reactions. A complete diabetes-care team is associated with a superior use of technology (fewer dropouts, increased CGM and advanced bolus use) which is, however, still used in a small percentage of patients.In Italy, the number of CSII-treated pediatric patients (PP) is growing more significantly when compared to adults. Only 60% of all patients are using advanced functions and 20% are using CGMs continuously. This confirms the great interest in diabetes technology that is growing in pediatric diabetologists. However, much improvement is warranted in the organization and specialized training of pediatric, adult and transitional facilities.


PubMed | University of Turin, Azienda Ospedaliera Citta della Salute e Della Science di Turin Molinette and Diabetology and Metabolism
Type: | Journal: Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals | Year: 2016

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.The aim of this paper is the discovery of new non-invasive biomarker for the monitoring of VHLD patients.We compared the urinary proteome of VHLD patients, ccRCC patients and healthy volunteers.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.A1AT and APOH could be promising non-invasive biomarkers.


Berardelli R.,Diabetology and Metabolism | Karamouzis I.,Diabetology and Metabolism | D'Angelo V.,Diabetology and Metabolism | Zichi C.,Diabetology and Metabolism | And 4 more authors.
Endocrine | Year: 2013

This clinical review will summarize the available data regarding the role of mineralocorticoid receptors (MRs) on the hypothalamus-pituitary-adrenal (HPA) axis control in physiological and pathological conditions and in the memory processes involved in the control and appraisal of a stress event. MRs are predominantly expressed in the limbic structures, with the hippocampus being the main localization, although MRs are also found at the hypothalamic level. It is known that hyppocampal MRs control the proactive feedback involved in the maintenance of the basal HPA activity, mainly at the nadir of the circadian rhythm. In physiological conditions, the administration of pharmacological doses of both MR antagonists and agonists is able to interact with the HPA activity, modifying the quiescent phase-nadir of the circadian rhythm, although some data in the literature do not support these observations. Also, in a physiological condition such as aging, an enhanced HPA axis activity is found in the time window, when MRs are predominantly occupied by cortisol circulating levels, possibly reflecting an MR impairment in this period of life. In pathology, major depression has been correlated to MR qualitative-quantitative alterations which could reflect differences on psychological and physiological responses, possibly predicting psychopathologies. Most of the remarks reported in this review seem to indicate, in agreement with animal data, a role played by MRs in the delicate control of the HPA axis in humans and the possible predisposition to the development of pathologies in case of their alterations. © 2012 Springer Science+Business Media, LLC.


Karamouzis I.,Diabetology and Metabolism | Berardelli R.,Diabetology and Metabolism | D'Angelo V.,Diabetology and Metabolism | Fussotto B.,Diabetology and Metabolism | And 6 more authors.
Clinical Endocrinology | Year: 2015

Objective Cushing Syndrome (CS) is implicated by increased cardiovascular risk (CVR) leading to increased morbidity and mortality. Oxidative stress (OS) and platelet activation (PA) are associated with increased CVR. However, scarce data of OS in CS exist. Our objective was to determine the oxidant-antioxidant balance in CS. Design Fourteen patients with CS at diagnosis and fourteen healthy subjects (NS) were evaluated OS by measuring plasma 15-F2t-Isoprostane (15-F2t-IsoP), PA by thromboxaneB2 levels (TXB2), and antioxidant reserve measuring total antioxidant capacity (TAC) and serum vitamin E. Results 15-F2t-IsoP and TXB2 levels were significantly higher (P < 0·01) in CS, while vitamin E levels were higher in NS (P < 0·03). 15-F2t-IsoP levels were significantly higher (P < 0·01) in complicated vs not-complicated CS and NS and significantly higher (P < 0·03) in CS not-complicated vs NS. TXB2 levels were significantly reduced (P < 0·03) in NS vs complicated and not-complicated CS. A negative correlation between Vitamin E and UFC was observed in CS (P < 0·05 r = -0·497). TXB2 correlated with glucose, HbA1c and T-score (P < 0·05 r = 0·512, P < 0·03 r = 0·527 and P < 0·01 r = 0·783, respectively) and HDL (P < 0·01 r = -0·651). 15-F2t-IsoP correlated with triglicerides, HbA1c and diastolic pressure (P < 0·01 r = 0·650, P < 0·03 r = 0·571 and P < 0·05 r = 0·498, respectively) and HDL (P < 0·03 r = -0·594). Conclusions This study emphasizes the major role of OS in CS. As our findings demonstrated that enhanced OS and PA take place in this rare metabolic disorder which is associated with increased CVR, it could be suggested that these biochemical alterations can further contribute in the pathogenesis of atherosclerosis, increased CVR and mortality in CS. © 2014 John Wiley & Sons Ltd.


PubMed | University of Turin, Azienda Ospedaliera Citta della Salute e della Science and Diabetology and Metabolism
Type: Journal Article | Journal: Journal of endocrinological investigation | Year: 2016

Mineralocorticoid receptors (MR) in the hippocampus display an important role in the control of hypothalamic-pituitary-adrenal (HPA) axis, mediating the proactive feedback of glucocorticoids (GC). Fludrocortisone (FC), a potent MR agonist, has been shown to decrease HPA activity through a hippocampal mechanism. Since it has been demonstrated that FC shows a significant inhibition of the HPA axis response to hCRH stimulus in normal subjects, also at doses usually administered as replacement therapy in patients with Addisons disease, an FC effect at MRs in human pituitary or a GR-pituitary agonism stronger than believed until now has been postulated.Ten patients affected by autoimmune Addisons disease received: (1) placebo p.o. + placebo i.v., (2) hydrocortisone (H) 10 mg p.o. + placebo i.v., (3) FC 0.1 mg p.o. + placebo i.v., (4) FC 0.1 mg and H 10 mg p.o. + placebo i.v. to verify a possible GR FC-mediated effect that might display a repercussion on the GC-replacement therapy.H reduced ACTH (p < 0.01) and increased cortisol levels (p < 0.01) with respect to the placebo session, while FC did not affect either ACTH or cortisol levels compared to placebo, and higher ACTH and lower cortisol levels (p < 0.03 and p < 0.01) were observed compared with the H session; furthermore the co-administration of FC + H showed ACTH and cortisol profiles similar to that observed during H alone.Our study showed a lack of FC effect on corticotrope secretion in Addisons disease, thus making unlikely the hypothesis of its GR pituitary agonism and the risk of glucocorticoid excess in primary adrenal insufficiency.


Malbois M.,University of Lausanne | Giusti V.,Diabetology and Metabolism | Suter M.,Hopital du Chablais | Pellaton C.,University of Lausanne | And 2 more authors.
Obesity Surgery | Year: 2010

Background: Screening for obstructive sleep apnea (OSA) is recommended as part of the preoperative assessment of obese patients scheduled for bariatric surgery. The objective of this study was to compare the sensitivity of oximetry alone versus portable polygraphy in the preoperative screening for OSA. Methods: Polygraphy (type III portable monitor) and oximetry data recorded as part of the preoperative assessment before bariatric surgery from 68 consecutive patients were reviewed. We compared the sensitivity of 3% or 4% desaturation index (oximetry alone) with the apnea-hypopnea index (AHI; polygraphy) to diagnose OSA and classify the patients as normal (<10 events per hour), mild to moderate (10-30 events per hour), or severe (>30 events per hour). Results: Using AHI, the prevalence of OSA (AHI>10 per hour) was 57.4%: 16.2% of the patients were classified as severe, 41.2% as mild to moderate, and 42.6% as normal. Using 3% desaturation index, 22.1% were classified as severe, 47.1% as mild to moderate, and 30.9% as normal. With 4% desaturation index, 17.6% were classified as severe, 32.4% as mild, and 50% as normal. Overall, 3% desaturation index compared to AHI yielded a 95% negative predictive value to rule out OSA (AHI>10 per hour) and a 100% sensitivity (0.73 positive predictive value) to detect severe OSA (AHI>30 per hour). Conclusions: Using oximetry with 3% desaturation index as a screening tool for OSA could allow us to rule out significant OSA in almost a third of the patients and to detect patients with severe OSA. This cheap and widely available technique could accelerate preoperative work-up of these patients. © 2009 Springer Science + Business Media, LLC.


Pennacchietti V.,A. O. U. Citta della Salute e della Science di Turin | Garzaro M.,Nose and Throat 1 | Grottoli S.,Diabetology and Metabolism | Pacca P.,A. O. U. Citta della Salute e della Science di Turin | And 3 more authors.
World Neurosurgery | Year: 2016

Background Pituitary tumors account for approximately 15% of primary intracranial neoplasms and often are diagnosed incidentally. Common sellar lesions are pituitary adenomas, craniopharyngiomas, and Rathke cleft cysts. Currently endoscopic transsphenoidal approaches are largely used, and many centers also use 3-dimensional (3D) technology, although additional results of long-term follow-up are still being accumulated. Methods We present a retrospective analysis of 104 patients with sellar lesions (57 male and 47 female, mean age 52 years) who underwent 3D endoscopic transsphenoidal surgery in our center from December 2011 to March 2015 and were followed up for a mean time of 18 months. Results A total of 16 patients were diagnosed with growth hormone-secreting adenomas, 9 with adrenocorticotropic hormone-secreting, 5 with prolactin-secreting, and 2 with thyroid-stimulating hormone-secreting tumors and 58 with nonsecreting pituitary adenomas. Five patients had Rathke cleft cysts, 5 craniopharyngiomas, 2 fibrous solitary tumors, 1 a metastasis, and 1 a chordoma. At baseline, 47 patients (45.2%) had hormonal changes and 52 (50%) had visual field changes. Complete resection was achieved in 73 patients (70.1%). Follow-up evaluation detected hormonal remission in 7 patients with Cushing disease (77.7%) and in 11 patients with acromegaly (68.7%). Complications were cerebrospinal fluid leak in 5 cases (4.8%) and transient diabetes insipidus in 6 cases (5.7%). A total of 55 patients (52.9%) were discharged less than 72 hours after surgery. Conclusions The use of an endoscopic endonasal approach with 3D technology provides several advantages relating to patient length of stay, rate of complications, postoperative recovery, and novice surgeons' training. Advantages of 3D endoscopy and long-term follow-up still need further elucidation. © 2016 Elsevier Inc. All rights reserved.


Gero D.,Hopital du Chablais | Dayer-Jankechova A.,CHUV | Worreth M.,Hopital du Jura | Giusti V.,Diabetology and Metabolism | Suter M.,Hopital du Chablais
Obesity Surgery | Year: 2014

Background: Gastric banding still represents one of the most widely used bariatric procedures. It provides acceptable weight loss in many patients, but has frequent long-term complications. Because different types of bands may lead to different results, we designed a randomized study to compare the Lapband® with the SAGB®. We hereby report on the long-term results. Methods: Between December 1998 and June 2002, 180 morbidly obese patients were randomized between Lapband® or SAGB®. Weight loss, long-term morbidity, and need for reoperation were evaluated. Results: Long-term weight loss did not differ between the two bands. Patients who maintained their band had an acceptable long-term weight loss of between 50 and 60 % EBMIL. In both groups, about half the patients developed long-term complications, with about 50 % requiring major redo surgery. There was no difference in the overall rates of long-term complications or failures between the two groups, but patients who had a Lapband® were significantly more prone to develop band slippage/pouch dilatation (13.3 versus 0 %, p < 0,001). Conclusions: Although in the absence of complication, gastric banding leads to acceptable weight loss; the long-term complication and major reoperation rates are very high independently from the type of band used or on the operative technique. Gastric banding leads to relatively poor overall long-term results and therefore should not be considered the procedure of choice for the treatment of morbid obesity. Patients should be informed of the limited overall weight loss and the very high complication rates. © 2013 Springer Science+Business Media New York.


PubMed | A. O. U. Citta della Salute e della Science di Turin, Nose and Throat 1 and Diabetology and Metabolism
Type: | Journal: World neurosurgery | Year: 2016

Pituitary tumors account for approximately 15% of primary intracranial neoplasms and often are diagnosed incidentally. Common sellar lesions are pituitary adenomas, craniopharyngiomas, and Rathke cleft cysts. Currently endoscopic transsphenoidal approaches are largely used, and many centers also use 3-dimensional (3D) technology, although additional results of long-term follow-up are still being accumulated.We present a retrospective analysis of 104 patients with sellar lesions (57 male and 47 female, mean age 52 years) who underwent 3D endoscopic transsphenoidal surgery in our center from December 2011 to March 2015 and were followed up for a mean time of 18months.A total of 16 patients were diagnosed with growth hormone-secreting adenomas, 9 with adrenocorticotropic hormone-secreting, 5 with prolactin-secreting, and 2 with thyroid-stimulating hormone-secreting tumors and 58 with nonsecreting pituitary adenomas. Five patients had Rathke cleft cysts, 5 craniopharyngiomas, 2 fibrous solitary tumors, 1 a metastasis, and 1 a chordoma. At baseline, 47 patients (45.2%) had hormonal changes and 52 (50%) had visual field changes. Complete resection was achieved in 73 patients (70.1%). Follow-up evaluation detected hormonal remission in 7 patients with Cushing disease (77.7%) and in 11 patients with acromegaly (68.7%). Complications were cerebrospinal fluid leak in 5 cases (4.8%) and transient diabetes insipidus in 6 cases (5.7%). Atotal of 55 patients (52.9%) were discharged less than 72 hours after surgery.The use of an endoscopic endonasal approach with 3D technology provides several advantages relating to patient length of stay, rate of complications, postoperative recovery, and novice surgeons training. Advantages of 3D endoscopy and long-term follow-up still need further elucidation.

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