Maurizio Castellano - Academia.edu (original) (raw)

Papers by Maurizio Castellano

Research paper thumbnail of What Role Can Process Mining Play in Recurrent Clinical Guidelines Issues? A Position Paper

International Journal of Environmental Research and Public Health, 2020

In the age of Evidence-Based Medicine, Clinical Guidelines (CGs) are recognized to be an indispen... more In the age of Evidence-Based Medicine, Clinical Guidelines (CGs) are recognized to be an indispensable tool to support physicians in their daily clinical practice. Medical Informatics is expected to play a relevant role in facilitating diffusion and adoption of CGs. However, the past pioneering approaches, often fragmented in many disciplines, did not lead to solutions that are actually exploited in hospitals. Process Mining for Healthcare (PM4HC) is an emerging discipline gaining the interest of healthcare experts, and seems able to deal with many important issues in representing CGs. In this position paper, we briefly describe the story and the state-of-the-art of CGs, and the efforts and results of the past approaches of medical informatics. Then, we describe PM4HC, and we answer questions like how can PM4HC cope with this challenge? Which role does PM4HC play and which rules should be employed for the PM4HC scientific community?

Research paper thumbnail of The Effects of Cow-Milk Protein Supplementation in Elderly Population: Systematic Review and Narrative Synthesis

Nutrients, 2020

Background. To review currently available evidence on the effect of cow-milk proteins supplementa... more Background. To review currently available evidence on the effect of cow-milk proteins supplementation (CPS) on health in the elderly. Methods. Five electronic databases (Pubmed, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov) were searched for studies about CPS among older people. All types of publications were included, with the exception of systematic reviews, meta-analyses, opinion letters, editorials, case reports, conference abstracts and comments. An additional search in Google Scholar and a manual review of the reference lists were performed. Results. Overall, 103 studies were included. Several studies explored the role of CPS in the preservation or improvement of muscle mass among healthy subjects (40 studies) and pre-frail, frail or sarcopenic patients (14), with evidence of beneficial effects. Other studies assessed the effect of CPS on bones (12), cardiovascular disease (8), inflamm-aging (7), chronic pulmonary disease (4), neurocognitive function (4), and v...

Research paper thumbnail of Transdermal nitroglycerin efficacy in patients with chronic stable angina pectoris as related to sympathetic and renin-angiotensin-aldosterone activity

European Heart Journal, 1992

The aim of this study was to evaluate the acute effects of transdermal nitroglycerin on the sympa... more The aim of this study was to evaluate the acute effects of transdermal nitroglycerin on the sympathetic and renin-angiotensin-aldosterone systems activity, in a group of patients with stable exercise induced angina pectoris. Eighteen outpatients (15M, 3F, age range 47-65 years) were included in this double-blind, randomized, crossover trial comparing the antianginal effects of a transdermal system delivering 20 mg.day-1 of nitroglycerin to an identical placebo. Plasma renin activity, plasma aldosterone and catecholamine concentrations were measured in resting basal conditions and at 4, 8, 24, and 32 h post-dosing. Patients were subdivided in two groups according to the increase in exercise duration after patch application greater than 30% (responders, n = 8) and less or equal to 30% (non-responders, n = 10) in respect to placebo. In responders plasma norepinephrine was slightly increased during transdermal nitroglycerin administration in comparison to placebo while no change was observed in plasma adrenaline and aldosterone concentrations and in plasma renin activity. In non-responders plasma norepinephrine levels significantly increased during nitroglycerin treatment in comparison with placebo. Multiple comparisons showed that this increase was significant at 4, 8 and 24 h post-dosing. Plasma epinephrine and aldosterone concentrations and plasma renin activity were also increased after nitroglycerin administration. In the population as a whole, a significant inverse correlation was found between the percent increase in exercise duration (active drug vs placebo) and the absolute values of plasma norepinephrine and aldosterone, 4 h post-dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Metformin-induced thyrotropin suppression is not associated with cardiac effects

Hormones, 2014

OBjECTIVE: Metformin treatment may induce a decrease/suppression in serum TSH levels, mimicking s... more OBjECTIVE: Metformin treatment may induce a decrease/suppression in serum TSH levels, mimicking sub-clinical hyperthyroidism (SHT). The aim of the present study was to retrospectively evaluate changes in several electrocardiographic indices in euthyroid subjects with diabetes who, after starting metformin treatment, developed a low serum TSH as compared to patients with SHT resulting from an underlying thyroid disease or TSH suppressive treatment with L-thyroxine. DEsIGn: Heart rate, P wave duration, P wave dispersion, Qtmax, Qtmin and Qt-dispersion were assessed in 23 patients with diabetes treated with metformin before and after 6 months of tsH-suppression and in 31 control patients with sHt. REsuLts: No significant changes in electrocardiographic parameters were observed from baseline to the TSH-suppression measurement. A significant difference in P wave duration (102.9±7.4 vs. 92.1±5.8 ms, p<0.001), P wave dispersion (13.1±3.4 vs. 7.1±3.5 ms, p<0.001), Qtmax (399±18 vs. 388±16 ms, p=0.024), Qtmin (341±14 vs. 350±17 ms, p=0.038) and Qt dispersion (49.9±9.6 vs. 30.9±9.2 ms, p<0.001) were observed between the control group with SHT and the group of diabetic patients with low serum levels of tsH. COnCLusIOns: Our results show that the TSH-suppressive effect observed in patients taking metformin is not associated with peripheral markers of thyroid hormone excess, at least at the cardiac level.

Research paper thumbnail of TSH Variability of Patients Affected by Differentiated Thyroid Cancer Treated with Levothyroxine Liquid Solution or Tablet Form

International Journal of Endocrinology, 2017

Background. Recent guidelines from the American Thyroid Association (ATA) indicate that, in many ... more Background. Recent guidelines from the American Thyroid Association (ATA) indicate that, in many patients affected by differentiated thyroid cancer (DTC), the serum TSH should be maintained between 0.1 and 0.5 mU/L. The purpose of this study was to evaluate the TSH variability of patients affected by DTC treated with liquid L-T4 formulation or in tablet form. Patients and Methods. Patients were eligible if (a) they were submitted to a total thyroidectomy and 131I remnant ablation for DTC in our institution and (b) they were classified low-risk patients according to ATA guidelines 2009. Patients were randomized (1 : 1) to receive treatment of hypothyroidism with liquid L-T4 or tablet form. The first check-up evaluation was made from 8 to 12 months after 131I remnant ablation. TSH values were established again after further 12 months. Results. A significant increase in TSH values (median) was observed in patients taking tablets [TSH (min–max): 0.28 (0.1–0.45) versus 0.34 (0.01–0.78) m...

Research paper thumbnail of Increased potency of neuropeptide y to antagonize α 2 -adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat

Neuroscience, 1997

The regulation by neuropeptide Y of 2-adrenoceptors in the nucleus tractus solitarii was evaluate... more The regulation by neuropeptide Y of 2-adrenoceptors in the nucleus tractus solitarii was evaluated in the adult normotensive Wistar Kyoto rat and the adult spontaneously hypertensive rat. The microinjection of a submaximal dose of l-noradrenaline (800 pmol in 50 nl) alone into the nucleus tractus solitarii produced a significant reduction in the mean arterial blood pressure in either strain. The threshold dose (1 pmol in 50 nl) of neuropeptide Y(1-36) for the vasodepressor response in the Wistar Kyoto rat was five times higher than that (0.2 pmol in 50 nl) in the spontaneously hypertensive rat. Furthermore, neuropeptide Y(1-36) at 0.2 pmol in 50 nl could significantly counteract the vasodepressor response to l-noradrenaline (800 pmol in 50 nl) in the spontaneously hypertensive rat, but not in the Wistar Kyoto rat, in which 1 pmol in 50 nl of neuropeptide Y(1-36) must be employed to counteract the vasodepressor response to l-noradrenaline (800 pmol in 50 nl), although the vasodepressor responses are of a similar magnitude. The in situ hybridization and quantitative receptor autoradiographical experiments showed that the 2A-adrenoceptor messenger RNA levels and the B max value of the 2-adrenoceptor agonist [ 3 H]p-aminoclonidine binding sites measured in the nucleus tractus solitarii of the spontaneously hypertensive rat were substantially lower than those in the Wistar Kyoto rat. The quantitative receptor autoradiographical results were consistent with the cardiovascular results and showed that in the spontaneously hypertensive rat, neuropeptide Y(1-36) at 1 nM led to a significant increase in the K d value of [ 3 H]p-aminoclonidine binding sites. In the Wistar Kyoto rat, neuropeptide Y(1-36) produced this effect only at 10 nM. The present study provides evidence for an increase of the potency of neuropeptide Y(1-36) to antagonistically modulate 2-adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat. This enhanced antagonistic action may partly be related to a reduction in the number of 2A-adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat, since a decrease has been observed in the 2A-adrenoceptor messenger RNA levels and the 2-adrenoceptor binding sites in the spontaneously hypertensive rat. This increased potency of neuropeptide Y(1-36) to antagonize 2-adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat may contribute to the development of high blood pressure in this hypertensive strain. 1998 IBRO. Published by Elsevier Science Ltd.

Research paper thumbnail of Prolonged Effects of Short-Term Fosinopril on Blood Pressure and Vascular Morphology and Function in Rats

American Journal of Hypertension, 1997

The aim of this study was to evaluate the delayed effects of an angiotensin converting enzyme (AC... more The aim of this study was to evaluate the delayed effects of an angiotensin converting enzyme (ACE) inhibitor on blood pressure and on structural and functional alterations in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). The ACE inhibitor fosinopril (25 mg/ kg/day) was administered according to three different schedules: in one group of SHR from 4 to 8 weeks of age (n ‫؍‬ 12), in a second group from 8 to 12 weeks of age (n ‫؍‬ 15), and in a third group from 4 to 12 weeks of age (n ‫؍‬ 12). Eighteen untreated SHR and 18 untreated Wistar-Kyoto rats served as controls. About half the animals in each group were killed at 13 weeks of age, and the remaining were killed at 38 weeks of age. After death, relative left ventricular mass (left ventricular weight/body weight) was calculated. Vascular morphology (media : lumen ratio) and function (responses to norepinephrine and acetylcholine) in mesenteric small resistance arteries were then assessed using a micromyographic technique. Short-term fosinopril, given either before or after the development of hypertension, persistently reduced (but did not normalize) systolic blood pressure, vascular structural alterations, and reactivity to norepinephrine in mesenteric resistance arteries in SHR. These favorable effects were maintained at least for 26 to 30 weeks after treatment withdrawal. The endothelium-dependent vasodilator response to acetylcholine was improved at 13 but not at 38 weeks of age, in treated SHR. Therefore, the vascular response to norepinephrine seems to be dependent mainly on the structure of the vessels, whereas endothelial function is probably more linked to the hemodynamic load.

Research paper thumbnail of Prevention of the development of endothelial dysfunction in small mesenteric arteries of SHR is not related to the reduction of vascular structural alterations induced by the antihypertensive treatment with an ACE inhibitor

American Journal of Hypertension, 1995

Research paper thumbnail of Effect of norepinephrine and acetylcholine intraarterial infusion in hypertensive patients on blood pressure variability, as evaluated by spectral analysis

American Journal of Hypertension, 1995

Aim: to evaluate the effects of the evening administration of Flunitrazepam 1 mg on blood pressur... more Aim: to evaluate the effects of the evening administration of Flunitrazepam 1 mg on blood pressure (BP) and heart rate (HR). Methods: 12 healthy volunteers aged 24-30 yr (4 M and 8 F) underwent 2 ABPM (Spacelabs 90207. start at 2 p.m. and measurement every 15 min.) one week from heach other. In both cases they slept from 11 p.m. to 7 a.m.: the first time they took a placebo tablet (P) at 10:30 p.m. while the 2nd one they took Flunitrazepam (F) I mg p.o. at the same hour. Results: were as follows: primary oxidative NE Percent

Research paper thumbnail of Reduction of minimal vascular resistance by antihypertensive treatment and response to noradrenaline and acetylcholine infusion in the forearm of essential hypertesive patients

American Journal of Hypertension, 1995

To investigate the relationship between tissue reninangiotensin system (RAS) and the local vasomo... more To investigate the relationship between tissue reninangiotensin system (RAS) and the local vasomotor tone of large arteries, we used in vitro isolated carotid arteries from 14-week-old

Research paper thumbnail of Effect of treatment with hypotensive and non hypotensive dose of lacidipine on structural alterations of small mesenteric arteries of spontaneously hypertensive rats

American Journal of Hypertension, 1995

The calcium antagonist nifedipine has been used in the treatment of high altitude pulmonary edema... more The calcium antagonist nifedipine has been used in the treatment of high altitude pulmonary edema. In the present study the effects of felodipine on blood pressure (BP) and cardiovascular responses to a cold pressor test were assessed at an altitude of 5200 m. 16 healthy climbers participated. A double blind randomized cross over design was used. Placebo or felodipine were taken for two days. There were no changes in blood pressure (mean+SD:125+15/89+13 vs. 127+17/86+15 m; Hg), heart~ate (82+12 vs.-81+10-beats/min) or oxygen satu~ation (86±3~s 86±13%) during felodipine treatment compared to placebo. Moreover, there were no changes in the cardiovascular responses to the cold pressor test. We conclude that felodipine is well tolerated in young normotensive high altitude climbers. There are no effects on blood pressure or cardiovascular reactivity.

Research paper thumbnail of Real-time Elastography

Journal of Ultrasound in Medicine, 2012

The aim of this study was to evaluate the predictive value of sonography and sonographic elastogr... more The aim of this study was to evaluate the predictive value of sonography and sonographic elastography in thyroid nodules with nondiagnostic cytologic findings.

Research paper thumbnail of Vascular Structural and Functional Alterations Before and After the Development of Hypertension in SHR

American Journal of Hypertension, 1994

The time-course of the development of vascular and cardiac hypertrophy, as well as of arterial dy... more The time-course of the development of vascular and cardiac hypertrophy, as well as of arterial dys function, in human and experimental hypertension is still unclear. Moreover, the interrelationships between structural and functional vascular alter ations are presently under debate. The aim of this study was to assess the arteriolar wall thickness and left ventricular mass as well as the vascular response to norepinephrine and acetylcholine in spontaneously hypertensive rats (SHR), before and after the development of hypertension, as com pared to age-matched normotensive Wistar-Kyoto rats (WKY). Seventeen SHR (4 to 12 weeks old) and 17 WKY were included in the study. Blood pressure was measured noninvasively. After kill ing the animals, relative left ventricular mass (RLVM) was calculated, and mesenteric arcades were dissected and mounted on a micromyograph. Functional and structural characteristics of the ves sels were measured: media thickness (MT), media/ lumen ratio (M/L), and wall tension in response to norepinephrine and acetylcholine. At 4 weeks of age, no difference in blood pres sure and RLVM between SHR and WKY was de tected, but MT and M/L of mesenteric small resis tance arteries were significantly greater in SHR. An increased response to norepinephrine was ob served in terms of wall tension, but not of active media stress at the two higher norepinephrine con centrations. No difference in the dose-response curve to acetylcholine between SHR and WKY was observed. At 8 and 12 weeks of age systolic blood pressure was significantly higher in SHR; RLVM, MT, and M/L were also higher at this stage. Small resistance arteries of SHR showed an increased re sponse to norepinephrine (in terms of wall ten sion, but not of active media stress) and a reduced response to acetylcholine with respect to WKY when evaluated at 12 weeks of age. In conclusion, we observed an evident vascular hypertrophy at 4 weeks of age, before the onset of increased cardiac weight and before the development of hyperten sion. An enhanced contractile response to norepi nephrine, related to vascular hypertrophy, was de tectable in 4-week-old SHR, whereas endothelial dysfunction, as expressed by the dose-response curve to acetylcholine, was not evident. Endotheli al dysfunction was observed only in 12-week-old SHR, after development of hypertension and car diac hypertrophy, supporting the hypothesis that a hemodynamic rather than a structural factor may be involved in its genesis.

Research paper thumbnail of Relationship Between Different Subpopulations of Circulating CD4+ T-lymphocytes and Microvascular Structural Alterations in Humans

American journal of hypertension, Jan 21, 2016

Different components of the immune system, including innate and adaptive immunity (T-effector lym... more Different components of the immune system, including innate and adaptive immunity (T-effector lymphocytes and T-regulatory lymphocytes-TREGs) may be involved in the development of hypertension. In addition, it was demonstrated in animal models that TREGs may prevent angiotensin II-induced hypertension and vascular injury/inflammation. However, no data are presently available in humans about possible relationships between T-lymphocyte subtypes and microvascular structural alterations. For this purpose, in the present study, we enrolled 24 normotensive subjects and 12 hypertensive patients undergoing an elective surgical intervention. No sign of local or systemic inflammation was present. All patients underwent a biopsy of subcutaneous fat during surgery. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph and the media to lumen ratio (M/L) was calculated. In addition, retinal arteriolar structure was evaluated noninvasively by scanning laser Doppler f...

Research paper thumbnail of Thyroid Hormone Profile in Patients Ingesting Soft Gel Capsule or Liquid Levothyroxine Formulations with Breakfast

International journal of endocrinology, 2016

Background. Recently, it has been shown that liquid L-T4 formulation can be ingested with breakfa... more Background. Recently, it has been shown that liquid L-T4 formulation can be ingested with breakfast. This study looked to extend these findings by investigating whether a soft gel capsule formulation of L-T4 could also be ingested at breakfast time. Methods. 60 patients (18-65 yrs), previously submitted to thyroidectomy for proven benign goitre in stable euthyroidism receiving liquid L-T4 therapy ingested with breakfast, were enrolled. TSH, fT4, and fT3 levels were assessed in all the patients who were switched from liquid L-T4 to a soft gel capsule formulation at the same dosage of L-T4. After 6 months, TSH, fT4, and fT3 levels were determined again. Results. There were no differences in TSH levels, but fT3 and fT4 levels during treatment with the soft gel capsule were significantly lower than those at enrolment with the liquid L-T4 formulation (TSH median (min-max): 1.9 (0.5-4.0) versus 2.2 (0.5-4.5) mIU/L, fT3: 2.5 (2.4-3.1) versus 2.7 (2.4-3.3) pg/mL, p < 0.05, and fT4: 9.9 (...

Research paper thumbnail of Levothyroxine liquid solution versus tablet form for replacement treatment in pregnant women

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, Jan 20, 2015

To evaluate the need and the magnitude of levothyroxine (LT4) increase in hypothyroid pregnant wo... more To evaluate the need and the magnitude of levothyroxine (LT4) increase in hypothyroid pregnant women on liquid compared to tablet formulations. Patients were recruited by searching our "thyroid patients" database. The selection criteria were as follows: a) pregnant women on treatment for hypothyroidism (both liquid and tablet LT4) who gave birth at our hospital between February 2012 and January 2014; b) thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels obtained at least 3 months before missed menstrual cycle, with a TSH value less than 2.5 mIU/L and c) TSH and FT4 obtained within 12 weeks of pregnancy, and each month subsequently. During pregnancy, 8/31 (25.5%) of the women had to increase the dosage of LT4. Of these, 7/17 (41.2%) were on LT4 replacement therapy with tablets, and 1/14 (7.1%) with liquid formulation (p = 0.038). Daily LT4 was significantly increased in the liquid group only (52.9 ± 19.5 versus 67.5 ± 19.2 mcg/day (p = 0.013). A logistic regr...

Research paper thumbnail of A Double-Blind Placebo-Controlled Trial of Liquid Thyroxine Ingested at Breakfast: Results of the TICO Study

Thyroid, 2016

Background: Levothyroxine (L-T4) is the recommended treatment for millions of hypothyroid patient... more Background: Levothyroxine (L-T4) is the recommended treatment for millions of hypothyroid patients. Current guidelines recommend that L-T4 tablets be taken in a fasting state, but inability to adhere to this often leads to poor therapy compliance. Methods: We conducted a randomized, double-blind, placebo-controlled, crossover trial in previously untreated hypothyroid patients randomly assigned to receive an oral solution of L-T4 either at least 30 minutes before

Research paper thumbnail of Increzione di ANP e ADH durante attivazione e deattivazione dei barocettori cardiopolmonari: modificazioni in presenza di ipertrofia ventricolare sinistra

Cardiologia (Rome, Italy)

Research paper thumbnail of Cardiac norepinephrine, β-adrenoceptors, and Giα-proteins in prehypertensive and hypertensive spontaneously hypertensive rats

Journal of Cardiovascular Pharmacology

ABSTRACT

Research paper thumbnail of Determinants of Subcutaneous Small Resistance Artery Structure in Hypertensive Patients

High Blood Pressure & Cardiovascular Prevention, 2005

Research paper thumbnail of What Role Can Process Mining Play in Recurrent Clinical Guidelines Issues? A Position Paper

International Journal of Environmental Research and Public Health, 2020

In the age of Evidence-Based Medicine, Clinical Guidelines (CGs) are recognized to be an indispen... more In the age of Evidence-Based Medicine, Clinical Guidelines (CGs) are recognized to be an indispensable tool to support physicians in their daily clinical practice. Medical Informatics is expected to play a relevant role in facilitating diffusion and adoption of CGs. However, the past pioneering approaches, often fragmented in many disciplines, did not lead to solutions that are actually exploited in hospitals. Process Mining for Healthcare (PM4HC) is an emerging discipline gaining the interest of healthcare experts, and seems able to deal with many important issues in representing CGs. In this position paper, we briefly describe the story and the state-of-the-art of CGs, and the efforts and results of the past approaches of medical informatics. Then, we describe PM4HC, and we answer questions like how can PM4HC cope with this challenge? Which role does PM4HC play and which rules should be employed for the PM4HC scientific community?

Research paper thumbnail of The Effects of Cow-Milk Protein Supplementation in Elderly Population: Systematic Review and Narrative Synthesis

Nutrients, 2020

Background. To review currently available evidence on the effect of cow-milk proteins supplementa... more Background. To review currently available evidence on the effect of cow-milk proteins supplementation (CPS) on health in the elderly. Methods. Five electronic databases (Pubmed, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov) were searched for studies about CPS among older people. All types of publications were included, with the exception of systematic reviews, meta-analyses, opinion letters, editorials, case reports, conference abstracts and comments. An additional search in Google Scholar and a manual review of the reference lists were performed. Results. Overall, 103 studies were included. Several studies explored the role of CPS in the preservation or improvement of muscle mass among healthy subjects (40 studies) and pre-frail, frail or sarcopenic patients (14), with evidence of beneficial effects. Other studies assessed the effect of CPS on bones (12), cardiovascular disease (8), inflamm-aging (7), chronic pulmonary disease (4), neurocognitive function (4), and v...

Research paper thumbnail of Transdermal nitroglycerin efficacy in patients with chronic stable angina pectoris as related to sympathetic and renin-angiotensin-aldosterone activity

European Heart Journal, 1992

The aim of this study was to evaluate the acute effects of transdermal nitroglycerin on the sympa... more The aim of this study was to evaluate the acute effects of transdermal nitroglycerin on the sympathetic and renin-angiotensin-aldosterone systems activity, in a group of patients with stable exercise induced angina pectoris. Eighteen outpatients (15M, 3F, age range 47-65 years) were included in this double-blind, randomized, crossover trial comparing the antianginal effects of a transdermal system delivering 20 mg.day-1 of nitroglycerin to an identical placebo. Plasma renin activity, plasma aldosterone and catecholamine concentrations were measured in resting basal conditions and at 4, 8, 24, and 32 h post-dosing. Patients were subdivided in two groups according to the increase in exercise duration after patch application greater than 30% (responders, n = 8) and less or equal to 30% (non-responders, n = 10) in respect to placebo. In responders plasma norepinephrine was slightly increased during transdermal nitroglycerin administration in comparison to placebo while no change was observed in plasma adrenaline and aldosterone concentrations and in plasma renin activity. In non-responders plasma norepinephrine levels significantly increased during nitroglycerin treatment in comparison with placebo. Multiple comparisons showed that this increase was significant at 4, 8 and 24 h post-dosing. Plasma epinephrine and aldosterone concentrations and plasma renin activity were also increased after nitroglycerin administration. In the population as a whole, a significant inverse correlation was found between the percent increase in exercise duration (active drug vs placebo) and the absolute values of plasma norepinephrine and aldosterone, 4 h post-dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Metformin-induced thyrotropin suppression is not associated with cardiac effects

Hormones, 2014

OBjECTIVE: Metformin treatment may induce a decrease/suppression in serum TSH levels, mimicking s... more OBjECTIVE: Metformin treatment may induce a decrease/suppression in serum TSH levels, mimicking sub-clinical hyperthyroidism (SHT). The aim of the present study was to retrospectively evaluate changes in several electrocardiographic indices in euthyroid subjects with diabetes who, after starting metformin treatment, developed a low serum TSH as compared to patients with SHT resulting from an underlying thyroid disease or TSH suppressive treatment with L-thyroxine. DEsIGn: Heart rate, P wave duration, P wave dispersion, Qtmax, Qtmin and Qt-dispersion were assessed in 23 patients with diabetes treated with metformin before and after 6 months of tsH-suppression and in 31 control patients with sHt. REsuLts: No significant changes in electrocardiographic parameters were observed from baseline to the TSH-suppression measurement. A significant difference in P wave duration (102.9±7.4 vs. 92.1±5.8 ms, p<0.001), P wave dispersion (13.1±3.4 vs. 7.1±3.5 ms, p<0.001), Qtmax (399±18 vs. 388±16 ms, p=0.024), Qtmin (341±14 vs. 350±17 ms, p=0.038) and Qt dispersion (49.9±9.6 vs. 30.9±9.2 ms, p<0.001) were observed between the control group with SHT and the group of diabetic patients with low serum levels of tsH. COnCLusIOns: Our results show that the TSH-suppressive effect observed in patients taking metformin is not associated with peripheral markers of thyroid hormone excess, at least at the cardiac level.

Research paper thumbnail of TSH Variability of Patients Affected by Differentiated Thyroid Cancer Treated with Levothyroxine Liquid Solution or Tablet Form

International Journal of Endocrinology, 2017

Background. Recent guidelines from the American Thyroid Association (ATA) indicate that, in many ... more Background. Recent guidelines from the American Thyroid Association (ATA) indicate that, in many patients affected by differentiated thyroid cancer (DTC), the serum TSH should be maintained between 0.1 and 0.5 mU/L. The purpose of this study was to evaluate the TSH variability of patients affected by DTC treated with liquid L-T4 formulation or in tablet form. Patients and Methods. Patients were eligible if (a) they were submitted to a total thyroidectomy and 131I remnant ablation for DTC in our institution and (b) they were classified low-risk patients according to ATA guidelines 2009. Patients were randomized (1 : 1) to receive treatment of hypothyroidism with liquid L-T4 or tablet form. The first check-up evaluation was made from 8 to 12 months after 131I remnant ablation. TSH values were established again after further 12 months. Results. A significant increase in TSH values (median) was observed in patients taking tablets [TSH (min–max): 0.28 (0.1–0.45) versus 0.34 (0.01–0.78) m...

Research paper thumbnail of Increased potency of neuropeptide y to antagonize α 2 -adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat

Neuroscience, 1997

The regulation by neuropeptide Y of 2-adrenoceptors in the nucleus tractus solitarii was evaluate... more The regulation by neuropeptide Y of 2-adrenoceptors in the nucleus tractus solitarii was evaluated in the adult normotensive Wistar Kyoto rat and the adult spontaneously hypertensive rat. The microinjection of a submaximal dose of l-noradrenaline (800 pmol in 50 nl) alone into the nucleus tractus solitarii produced a significant reduction in the mean arterial blood pressure in either strain. The threshold dose (1 pmol in 50 nl) of neuropeptide Y(1-36) for the vasodepressor response in the Wistar Kyoto rat was five times higher than that (0.2 pmol in 50 nl) in the spontaneously hypertensive rat. Furthermore, neuropeptide Y(1-36) at 0.2 pmol in 50 nl could significantly counteract the vasodepressor response to l-noradrenaline (800 pmol in 50 nl) in the spontaneously hypertensive rat, but not in the Wistar Kyoto rat, in which 1 pmol in 50 nl of neuropeptide Y(1-36) must be employed to counteract the vasodepressor response to l-noradrenaline (800 pmol in 50 nl), although the vasodepressor responses are of a similar magnitude. The in situ hybridization and quantitative receptor autoradiographical experiments showed that the 2A-adrenoceptor messenger RNA levels and the B max value of the 2-adrenoceptor agonist [ 3 H]p-aminoclonidine binding sites measured in the nucleus tractus solitarii of the spontaneously hypertensive rat were substantially lower than those in the Wistar Kyoto rat. The quantitative receptor autoradiographical results were consistent with the cardiovascular results and showed that in the spontaneously hypertensive rat, neuropeptide Y(1-36) at 1 nM led to a significant increase in the K d value of [ 3 H]p-aminoclonidine binding sites. In the Wistar Kyoto rat, neuropeptide Y(1-36) produced this effect only at 10 nM. The present study provides evidence for an increase of the potency of neuropeptide Y(1-36) to antagonistically modulate 2-adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat. This enhanced antagonistic action may partly be related to a reduction in the number of 2A-adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat, since a decrease has been observed in the 2A-adrenoceptor messenger RNA levels and the 2-adrenoceptor binding sites in the spontaneously hypertensive rat. This increased potency of neuropeptide Y(1-36) to antagonize 2-adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat may contribute to the development of high blood pressure in this hypertensive strain. 1998 IBRO. Published by Elsevier Science Ltd.

Research paper thumbnail of Prolonged Effects of Short-Term Fosinopril on Blood Pressure and Vascular Morphology and Function in Rats

American Journal of Hypertension, 1997

The aim of this study was to evaluate the delayed effects of an angiotensin converting enzyme (AC... more The aim of this study was to evaluate the delayed effects of an angiotensin converting enzyme (ACE) inhibitor on blood pressure and on structural and functional alterations in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). The ACE inhibitor fosinopril (25 mg/ kg/day) was administered according to three different schedules: in one group of SHR from 4 to 8 weeks of age (n ‫؍‬ 12), in a second group from 8 to 12 weeks of age (n ‫؍‬ 15), and in a third group from 4 to 12 weeks of age (n ‫؍‬ 12). Eighteen untreated SHR and 18 untreated Wistar-Kyoto rats served as controls. About half the animals in each group were killed at 13 weeks of age, and the remaining were killed at 38 weeks of age. After death, relative left ventricular mass (left ventricular weight/body weight) was calculated. Vascular morphology (media : lumen ratio) and function (responses to norepinephrine and acetylcholine) in mesenteric small resistance arteries were then assessed using a micromyographic technique. Short-term fosinopril, given either before or after the development of hypertension, persistently reduced (but did not normalize) systolic blood pressure, vascular structural alterations, and reactivity to norepinephrine in mesenteric resistance arteries in SHR. These favorable effects were maintained at least for 26 to 30 weeks after treatment withdrawal. The endothelium-dependent vasodilator response to acetylcholine was improved at 13 but not at 38 weeks of age, in treated SHR. Therefore, the vascular response to norepinephrine seems to be dependent mainly on the structure of the vessels, whereas endothelial function is probably more linked to the hemodynamic load.

Research paper thumbnail of Prevention of the development of endothelial dysfunction in small mesenteric arteries of SHR is not related to the reduction of vascular structural alterations induced by the antihypertensive treatment with an ACE inhibitor

American Journal of Hypertension, 1995

Research paper thumbnail of Effect of norepinephrine and acetylcholine intraarterial infusion in hypertensive patients on blood pressure variability, as evaluated by spectral analysis

American Journal of Hypertension, 1995

Aim: to evaluate the effects of the evening administration of Flunitrazepam 1 mg on blood pressur... more Aim: to evaluate the effects of the evening administration of Flunitrazepam 1 mg on blood pressure (BP) and heart rate (HR). Methods: 12 healthy volunteers aged 24-30 yr (4 M and 8 F) underwent 2 ABPM (Spacelabs 90207. start at 2 p.m. and measurement every 15 min.) one week from heach other. In both cases they slept from 11 p.m. to 7 a.m.: the first time they took a placebo tablet (P) at 10:30 p.m. while the 2nd one they took Flunitrazepam (F) I mg p.o. at the same hour. Results: were as follows: primary oxidative NE Percent

Research paper thumbnail of Reduction of minimal vascular resistance by antihypertensive treatment and response to noradrenaline and acetylcholine infusion in the forearm of essential hypertesive patients

American Journal of Hypertension, 1995

To investigate the relationship between tissue reninangiotensin system (RAS) and the local vasomo... more To investigate the relationship between tissue reninangiotensin system (RAS) and the local vasomotor tone of large arteries, we used in vitro isolated carotid arteries from 14-week-old

Research paper thumbnail of Effect of treatment with hypotensive and non hypotensive dose of lacidipine on structural alterations of small mesenteric arteries of spontaneously hypertensive rats

American Journal of Hypertension, 1995

The calcium antagonist nifedipine has been used in the treatment of high altitude pulmonary edema... more The calcium antagonist nifedipine has been used in the treatment of high altitude pulmonary edema. In the present study the effects of felodipine on blood pressure (BP) and cardiovascular responses to a cold pressor test were assessed at an altitude of 5200 m. 16 healthy climbers participated. A double blind randomized cross over design was used. Placebo or felodipine were taken for two days. There were no changes in blood pressure (mean+SD:125+15/89+13 vs. 127+17/86+15 m; Hg), heart~ate (82+12 vs.-81+10-beats/min) or oxygen satu~ation (86±3~s 86±13%) during felodipine treatment compared to placebo. Moreover, there were no changes in the cardiovascular responses to the cold pressor test. We conclude that felodipine is well tolerated in young normotensive high altitude climbers. There are no effects on blood pressure or cardiovascular reactivity.

Research paper thumbnail of Real-time Elastography

Journal of Ultrasound in Medicine, 2012

The aim of this study was to evaluate the predictive value of sonography and sonographic elastogr... more The aim of this study was to evaluate the predictive value of sonography and sonographic elastography in thyroid nodules with nondiagnostic cytologic findings.

Research paper thumbnail of Vascular Structural and Functional Alterations Before and After the Development of Hypertension in SHR

American Journal of Hypertension, 1994

The time-course of the development of vascular and cardiac hypertrophy, as well as of arterial dy... more The time-course of the development of vascular and cardiac hypertrophy, as well as of arterial dys function, in human and experimental hypertension is still unclear. Moreover, the interrelationships between structural and functional vascular alter ations are presently under debate. The aim of this study was to assess the arteriolar wall thickness and left ventricular mass as well as the vascular response to norepinephrine and acetylcholine in spontaneously hypertensive rats (SHR), before and after the development of hypertension, as com pared to age-matched normotensive Wistar-Kyoto rats (WKY). Seventeen SHR (4 to 12 weeks old) and 17 WKY were included in the study. Blood pressure was measured noninvasively. After kill ing the animals, relative left ventricular mass (RLVM) was calculated, and mesenteric arcades were dissected and mounted on a micromyograph. Functional and structural characteristics of the ves sels were measured: media thickness (MT), media/ lumen ratio (M/L), and wall tension in response to norepinephrine and acetylcholine. At 4 weeks of age, no difference in blood pres sure and RLVM between SHR and WKY was de tected, but MT and M/L of mesenteric small resis tance arteries were significantly greater in SHR. An increased response to norepinephrine was ob served in terms of wall tension, but not of active media stress at the two higher norepinephrine con centrations. No difference in the dose-response curve to acetylcholine between SHR and WKY was observed. At 8 and 12 weeks of age systolic blood pressure was significantly higher in SHR; RLVM, MT, and M/L were also higher at this stage. Small resistance arteries of SHR showed an increased re sponse to norepinephrine (in terms of wall ten sion, but not of active media stress) and a reduced response to acetylcholine with respect to WKY when evaluated at 12 weeks of age. In conclusion, we observed an evident vascular hypertrophy at 4 weeks of age, before the onset of increased cardiac weight and before the development of hyperten sion. An enhanced contractile response to norepi nephrine, related to vascular hypertrophy, was de tectable in 4-week-old SHR, whereas endothelial dysfunction, as expressed by the dose-response curve to acetylcholine, was not evident. Endotheli al dysfunction was observed only in 12-week-old SHR, after development of hypertension and car diac hypertrophy, supporting the hypothesis that a hemodynamic rather than a structural factor may be involved in its genesis.

Research paper thumbnail of Relationship Between Different Subpopulations of Circulating CD4+ T-lymphocytes and Microvascular Structural Alterations in Humans

American journal of hypertension, Jan 21, 2016

Different components of the immune system, including innate and adaptive immunity (T-effector lym... more Different components of the immune system, including innate and adaptive immunity (T-effector lymphocytes and T-regulatory lymphocytes-TREGs) may be involved in the development of hypertension. In addition, it was demonstrated in animal models that TREGs may prevent angiotensin II-induced hypertension and vascular injury/inflammation. However, no data are presently available in humans about possible relationships between T-lymphocyte subtypes and microvascular structural alterations. For this purpose, in the present study, we enrolled 24 normotensive subjects and 12 hypertensive patients undergoing an elective surgical intervention. No sign of local or systemic inflammation was present. All patients underwent a biopsy of subcutaneous fat during surgery. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph and the media to lumen ratio (M/L) was calculated. In addition, retinal arteriolar structure was evaluated noninvasively by scanning laser Doppler f...

Research paper thumbnail of Thyroid Hormone Profile in Patients Ingesting Soft Gel Capsule or Liquid Levothyroxine Formulations with Breakfast

International journal of endocrinology, 2016

Background. Recently, it has been shown that liquid L-T4 formulation can be ingested with breakfa... more Background. Recently, it has been shown that liquid L-T4 formulation can be ingested with breakfast. This study looked to extend these findings by investigating whether a soft gel capsule formulation of L-T4 could also be ingested at breakfast time. Methods. 60 patients (18-65 yrs), previously submitted to thyroidectomy for proven benign goitre in stable euthyroidism receiving liquid L-T4 therapy ingested with breakfast, were enrolled. TSH, fT4, and fT3 levels were assessed in all the patients who were switched from liquid L-T4 to a soft gel capsule formulation at the same dosage of L-T4. After 6 months, TSH, fT4, and fT3 levels were determined again. Results. There were no differences in TSH levels, but fT3 and fT4 levels during treatment with the soft gel capsule were significantly lower than those at enrolment with the liquid L-T4 formulation (TSH median (min-max): 1.9 (0.5-4.0) versus 2.2 (0.5-4.5) mIU/L, fT3: 2.5 (2.4-3.1) versus 2.7 (2.4-3.3) pg/mL, p < 0.05, and fT4: 9.9 (...

Research paper thumbnail of Levothyroxine liquid solution versus tablet form for replacement treatment in pregnant women

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, Jan 20, 2015

To evaluate the need and the magnitude of levothyroxine (LT4) increase in hypothyroid pregnant wo... more To evaluate the need and the magnitude of levothyroxine (LT4) increase in hypothyroid pregnant women on liquid compared to tablet formulations. Patients were recruited by searching our "thyroid patients" database. The selection criteria were as follows: a) pregnant women on treatment for hypothyroidism (both liquid and tablet LT4) who gave birth at our hospital between February 2012 and January 2014; b) thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels obtained at least 3 months before missed menstrual cycle, with a TSH value less than 2.5 mIU/L and c) TSH and FT4 obtained within 12 weeks of pregnancy, and each month subsequently. During pregnancy, 8/31 (25.5%) of the women had to increase the dosage of LT4. Of these, 7/17 (41.2%) were on LT4 replacement therapy with tablets, and 1/14 (7.1%) with liquid formulation (p = 0.038). Daily LT4 was significantly increased in the liquid group only (52.9 ± 19.5 versus 67.5 ± 19.2 mcg/day (p = 0.013). A logistic regr...

Research paper thumbnail of A Double-Blind Placebo-Controlled Trial of Liquid Thyroxine Ingested at Breakfast: Results of the TICO Study

Thyroid, 2016

Background: Levothyroxine (L-T4) is the recommended treatment for millions of hypothyroid patient... more Background: Levothyroxine (L-T4) is the recommended treatment for millions of hypothyroid patients. Current guidelines recommend that L-T4 tablets be taken in a fasting state, but inability to adhere to this often leads to poor therapy compliance. Methods: We conducted a randomized, double-blind, placebo-controlled, crossover trial in previously untreated hypothyroid patients randomly assigned to receive an oral solution of L-T4 either at least 30 minutes before

Research paper thumbnail of Increzione di ANP e ADH durante attivazione e deattivazione dei barocettori cardiopolmonari: modificazioni in presenza di ipertrofia ventricolare sinistra

Cardiologia (Rome, Italy)

Research paper thumbnail of Cardiac norepinephrine, β-adrenoceptors, and Giα-proteins in prehypertensive and hypertensive spontaneously hypertensive rats

Journal of Cardiovascular Pharmacology

ABSTRACT

Research paper thumbnail of Determinants of Subcutaneous Small Resistance Artery Structure in Hypertensive Patients

High Blood Pressure & Cardiovascular Prevention, 2005