- via S. Mattia 20
I - 35121 Padova (Italy) - 39+3356150955
Andrea Semplicini
Università degli Studi di Padova, Department of medicine, Faculty Member
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Research Interests: Medicine and Task Force
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Patients with renal failure and undergoing hemo- (HD) or peritoneal dialysis are under oxidative stress which is thought to contribute to the long-term complications noted in this patient population. One effect of HD-induced oxidative... more
Patients with renal failure and undergoing hemo- (HD) or peritoneal dialysis are under oxidative stress which is thought to contribute to the long-term complications noted in this patient population. One effect of HD-induced oxidative stress is via red blood cell (RBC) membrane lipid peroxidation leading to RBC destruction and anemia. Interaction of this oxidative stress with epoetin (EPO) treatment to increase RBC number and Hb concentration remains unexplored. This preliminary study used RT-PCR as well as colorimetric based assay approaches to evaluate the effect of EPO-alpha treatment on markers of oxidative stress in hemodialysis patients. Eighteen patients (12 males, 6 females, age range 45 - 68), were treated with EPO-alpha (Eprex) 50 UI/kg thrice weekly over an 8-month study period. Monocytes were isolated at baseline, then monthly thereafter, monocyte heme-oxygenase-1 (HO-1) and plasma Hb and antioxidant power (AOP) were determined. Treatment with EPO increased Hb (9.4 +/- 0.7 g/dl to 10.9 +/- 0.5, mean +/- SD p < 0.001). In addition, both monocyte HO-1 mRNA (0.34 +/- 0.08 vs. 0.59 +/- 0.02 d.u. p < 0.001) and plasma AOP (1,379.8 +/- 175 micromol/l to 1,624 +/- 170, p < 0.04) increased. While AOP changes showed no correlation with other indices, increases in HO-1 and Hb were positively correlated using 2 different measures: delta Hb (peak Hb - baseline Hb) vs. delta HO-1 (peak HO-1 mRNA - baseline HO-1 mRNA) as well as delta Hb(5 months-baseline) vs. delta HO-1 (5 months - baseline) mRNA (r = 0.81, p < 0.001 and r = 0.76, p < 0.001; respectively). In conclusion, the increases upon EPO treatment of both HO-1 gene expression and plasma AOP as well as the significant correlation between delta Hb and delta HO-1 mRNA suggest that EPO treatment reduces oxidative stress via a combination of effects. These could potentially include effects on oxidative stress directly as well as effects on the levels and types of antioxidants present in plasma.
Research Interests: Endocrinology, Chemistry, Membrane Proteins, Oxidative Stress, Medicine, and 15 moreAntioxidants, Erythropoietin, Humans, Internal Medicine, Female, Hemodialysis, Male, Heme Oxygenase, Hemoglobin, Aged, Middle Aged, Adult, Recombinant Proteins, Renal Dialysis, and Pharmacology and pharmaceutical sciences
The increased red blood cell Li+/Na+ exchange found in a subgroup of patients with essential hypertension (EH) may reflect an increased activity of the Na+/H+ exchange. The maximal velocity of the red cells' Na+/H+ (Na+ influx... more
The increased red blood cell Li+/Na+ exchange found in a subgroup of patients with essential hypertension (EH) may reflect an increased activity of the Na+/H+ exchange. The maximal velocity of the red cells' Na+/H+ (Na+ influx promoted by an outward H+ gradient) and Li+/Na+ (Li+ efflux promoted by external Na+) exchange were therefore measured in 41 EH and in 21 normotensive controls (NT). Both transporters were significantly higher in EH than in NT (74 +/- 39 mmol/L cell x h v 43 +/- 27 for the former, P less than .03, and 0.35 +/- 0.16 v 0.26 +/- 0.10 for the latter, P less than .05). Even though more than 100 times faster, Na+/H+ exchange was weakly but significantly correlated to Li+/Na+ exchange (r = 0.29, P less than .05). Proximal tubule Na+ reabsorption (fractional renal Li+ reabsorption) was significantly greater in EH than in NT (0.78 +/- 0.07, n = 32, v 0.73 +/- 0.06, n = 10, P less than .05) but it was not correlated to either the red cells' Na+/H+ or Li+/Na+ exchanges. Therefore, hyperactivity of Na+/H+ exchange in EH may play a role in blood pressure elevation through mechanisms other than stimulation of renal Na+ reabsorption.
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P124 Attempts to understand the pathogenesis of essential hypertension have focused on identifying intermediate phenotypes such as defects in cation metabolism. Elevated red blood cell sodium-lithium countertransport (SLC) activity is... more
P124 Attempts to understand the pathogenesis of essential hypertension have focused on identifying intermediate phenotypes such as defects in cation metabolism. Elevated red blood cell sodium-lithium countertransport (SLC) activity is frequently present in hypertensive patients. Cytosolic calcium (Ca cyt ) is also elevated in blood cells from hypertensive patients. However, despite their frequent occurrence in hypertensive patients, these two markers of cation homeostasis have not been simultaneously investigated in the same individuals. We studied lymphocyte Ca cyt and red cell SLC activity in hypertensive (n = 43) and normal subjects (n = 22) to determine whether elevated SLC activity and lymphocyte Ca cyt occur in the same individuals. Red cell SLC and lymphocyte Ca cyt were significantly ( P <0.01) higher in the hypertensive patients vs. normotensives. However, SLC activity and Ca cyt were significantly but inversely correlated (r=-0.42, P <0.01). Patients with low Ca cyt (84 ± 5 nM) had elevated SLC (0.41 ± 0.03 mmol/L cell x h, P< 0.05) whereas those with elevated Ca cyt (188 ± 15) had lower SLC (0.32 ± 0.03 mmol/L cell x h, P< 0.05). We then compared both phenotypes to a separate intermediate phenotype, fasting insulin. SLC and fasting insulin levels were significantly and positively correlated (r=0.45, P <0.01), consistent with prior studies showing elevated SLC activity in the setting of hyperinsulinemia. Ca cyt was inversely correlated with fasting insulin (r=-0.55, P <0.001). Individuals with insulin levels above the median (15 mU/ml) had significantly ( P <0.01) higher SLC activity (0.43 ± 0.03 vs . 0.28 ± 0.02 mmol/L cell x h) and significantly ( P =0.017) lower Ca cyt (177 ± 18 vs. 105 ± 8 nM). Thus, elevated SLC activity and elevated lymphocyte Ca cyt are separate and distinct ion transport phenotypes in hypertensive patients, but they are linked through a relationship to hyperinsulinemia that is direct with SLC and inverse with lymphocyte Ca cyt .
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It has been reported that patients with type I insulin dependent diabetes mellitus (IDDM) are characterized by reduced Na+ excretion during water immersion and saline infusion and abnormal glomerulo-tubular balance. Aims of the present... more
It has been reported that patients with type I insulin dependent diabetes mellitus (IDDM) are characterized by reduced Na+ excretion during water immersion and saline infusion and abnormal glomerulo-tubular balance. Aims of the present study were therefore to investigate firstly the fractional tubular Na+ reabsorption during saline infusion to clarify the altered tubular site and secondly the glomerulo-tubular balance during acute increase of glomerular filtration rate induced by sodium acetoacetate infusion in IDDM. During saline and euglycaemic glucose clamp, after an overnight fast, glomerular filtration rate, renal plasma flow, filtration fraction and plasma sodium were 99 +/- 15 ml min-1 1.73 m-2, 452 +/- 109 ml min-1 1.73 m-2, 0.23 +/- 0.04 and 142 +/- 8 mmol l-1 (Mean +/- SD) in 10 type I insulin dependent diabetic patients and 96 +/- 18, 452 +/- 87, 0.21 +/- 0.02, 143 +/- 2 in five matched normal subjects, respectively. The lithium and sodium clearances were significantly lower in diabetic patients than in normal subjects (23 +/- 5 ml min-1 1.73 m-2 vs 28 +/- 6, p less than 0.05 and 1.1 +/- 0.4 vs 1.6 +/- 0.3, p less than 0.01 respectively). The fractional lithium reabsorption was greater (0.77 +/- 0.04 vs 0.72 +/- 0.03, p less than 0.05) and the distal fractional sodium reabsorption smaller (0.22 +/- 0.04 vs 0.27 +/- 0.03, p less than 0.01) in the diabetic patients compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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In the red blood cell membrane, sodium-proton exchange (NHE-1) exchanges intracellular H(+), Li(+), and Na(+) with extracellular Na(+). In hypertensives (HT), the maximal velocity of translocation (V max)of Na(+)/H(+) and of Na(+)/Li(+)... more
In the red blood cell membrane, sodium-proton exchange (NHE-1) exchanges intracellular H(+), Li(+), and Na(+) with extracellular Na(+). In hypertensives (HT), the maximal velocity of translocation (V max)of Na(+)/H(+) and of Na(+)/Li(+) exchange modes are higher, while apparent affinity for external Na(+) of Na(+)/Li(+) exchange and Hill's coefficient for H(+) activation of Na(+)/H(+) exchange are lower than in normotensive subjects (NT). We have therefore examined the effects of protein kinase C (PKC) and insulin on red blood cell membrane phosphorylation and on the kinetic properties of cation heteroexchange. In red cell from NT, PMA-induced activation of PKC reduced K(m) for H(+) of NHE but it did not affect V(max) and K(m) for Na(+). In red cell from HT, PMA-induced a greater PKC stimulation and membrane phosphorylation of band 3,4.1,4.9 than in NT and it did not significantly reduced K(m) for H(i). On the contrary, in HT PKC activation significantly increased Hill's coefficient of NHE. The larger activation of PKC in HT could be due to downregulation secondary to higher membrane calpain activity. Incubation of red cells with insulin decreases K(m) for external Na(+) and increases V(max) of Na(+)/Li(+) exchange. Therefore, we have examined the relationships between Na(+)-activation kinetics of Na(+)/Li(+) exchange and fasting insulin levels. Na(+)-stimulated Li(+) efflux was studied by raising Na(+)up to 300 mM isoosmotically to measure K(m) for Na(+) and V (max). Li(+) efflux saturated at 150 mM external Na(+)in NT but not in HT because in HT it exhibited a two fold higher Na(+) Km. V(max) was higher in HT than in NT. In hyperinsulinemic (fasting insulin > 10 mu U/ml) HT, V(max) and Na(+) Km were higher than in normoinsulinemic HT. In NT, hyperinsulinemia was not associated to abnormal kinetic properties of Na(+)/Li(+)exchange. Stepwise multiple regression analysis confirmed that the main determinants of a high Km were blood pressure and insulin. Our results show that posttranslational effects of PKC and insulin affect the kinetic properties of NHE-1 in red blood cells and suggest that the differences observed between hypertensives and normotensive subjects can be accounted for by PKC activation and insulin exposure.
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We recently reported that incubation of red blood cells with insulin markedly decreases the affinity for external Na + and increases the maximal transport rate ( V max ) of Na + -Li + countertransport. The association of hypertension with... more
We recently reported that incubation of red blood cells with insulin markedly decreases the affinity for external Na + and increases the maximal transport rate ( V max ) of Na + -Li + countertransport. The association of hypertension with insulin resistance and its compensatory hyperinsulinemia led us to investigate the relationship between insulin levels in vivo and the Na + activation kinetics of this antiporter. We studied normotensive (n=28) and hypertensive (n=25) subjects after they had fasted overnight and determined their plasma glucose and insulin concentrations. Insulin levels were higher in the hypertensive subjects (11.7±1.5 μU/mL, mean±SEM) than in the normotensive subjects (8.2±1.2 μU/mL), but glucose levels were similar and within normal limits. Antiporter activity was measured as sodium-stimulated Li + efflux by a new procedure that uses isosmotic conditions to raise external Na + to 280 mmol/L. In normotensive subjects, V max was reached between 50 and 100 mmol/L Na + , whereas in most hypertensive subjects, Na + concentrations higher than 150 mmol/L were needed. This different kinetic behavior was because the Na + concentration for half-maximal activation ( K m ) was twofold higher in hypertensive subjects (58.9±5.3 mmol/L) than in normotensive subjects (29.8±2.6 mmol/L, P <.001). Hypertensive subjects with fasting insulin levels greater than 10 μU/mL (n=12) had a higher K m for Na + than subjects with insulin levels less than 10 μU/mL (n=13) (73.4±8.7 versus 45.6±3.9 mmol/L, respectively, P <.01) and similar V max (0.57±0.05 versus 0.41±0.05 mmol · L −1 · h −1 ). In contrast, normotensive subjects with insulin levels greater than 10 μU/mL (n=6) had V max and K m values similar to those with insulin levels less than 10 μU/mL (n=22). Simple regression analysis showed that body mass index, insulin, and blood pressure correlated with both kinetic parameters. However, stepwise multiple regression analysis showed that the main determinant of V max was blood pressure and for K m , blood pressure and insulin levels. The association of a low affinity for Na + with in vivo hyperinsulinemia and its concomitant insulin resistance observed in hypertensive subjects agrees with the in vitro effects of insulin on this antiporter.
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Research Interests: Endocrinology, Genetics, Oxidative Stress, Medicine, Signal Transduction, and 15 moreHumans, Internal Medicine, Reactive Oxygen Species, Female, Male, Polymerase Chain Reaction, Peroxynitrite, Membrane transport proteins, NADPH oxidase, Clinical Sciences, Middle Aged, Adult, Transforming Growth Factor Beta, Angiotensin II, and Bartter syndrome
P124 Attempts to understand the pathogenesis of essential hypertension have focused on identifying intermediate phenotypes such as defects in cation metabolism. Elevated red blood cell sodium-lithium countertransport (SLC) activity is... more
P124 Attempts to understand the pathogenesis of essential hypertension have focused on identifying intermediate phenotypes such as defects in cation metabolism. Elevated red blood cell sodium-lithium countertransport (SLC) activity is frequently present in hypertensive patients. Cytosolic calcium (Ca cyt ) is also elevated in blood cells from hypertensive patients. However, despite their frequent occurrence in hypertensive patients, these two markers of cation homeostasis have not been simultaneously investigated in the same individuals. We studied lymphocyte Ca cyt and red cell SLC activity in hypertensive (n = 43) and normal subjects (n = 22) to determine whether elevated SLC activity and lymphocyte Ca cyt occur in the same individuals. Red cell SLC and lymphocyte Ca cyt were significantly ( P <0.01) higher in the hypertensive patients vs. normotensives. However, SLC activity and Ca cyt were significantly but inversely correlated (r=-0.42, P <0.01). Patients with low Ca cyt (84 ± 5 nM) had elevated SLC (0.41 ± 0.03 mmol/L cell x h, P< 0.05) whereas those with elevated Ca cyt (188 ± 15) had lower SLC (0.32 ± 0.03 mmol/L cell x h, P< 0.05). We then compared both phenotypes to a separate intermediate phenotype, fasting insulin. SLC and fasting insulin levels were significantly and positively correlated (r=0.45, P <0.01), consistent with prior studies showing elevated SLC activity in the setting of hyperinsulinemia. Ca cyt was inversely correlated with fasting insulin (r=-0.55, P <0.001). Individuals with insulin levels above the median (15 mU/ml) had significantly ( P <0.01) higher SLC activity (0.43 ± 0.03 vs . 0.28 ± 0.02 mmol/L cell x h) and significantly ( P =0.017) lower Ca cyt (177 ± 18 vs. 105 ± 8 nM). Thus, elevated SLC activity and elevated lymphocyte Ca cyt are separate and distinct ion transport phenotypes in hypertensive patients, but they are linked through a relationship to hyperinsulinemia that is direct with SLC and inverse with lymphocyte Ca cyt .
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Research Interests: Medicine, Logistic Regression, Discriminant Analysis, Humans, Internal Medicine, and 15 moreFemale, Clinical, Male, Clinical Sciences, Middle Aged, Adult, Analysis of Variance, Clinical Endocrinology, Angiotensin Converting Enzyme Inhibitors, Predictive value of tests, Hyperaldosteronism, Captopril, Model fitting, mass Screening, and Paediatrics and reproductive medicine
Research Interests: Cardiology, Adolescent, Medicine, Gene expression, Humans, and 15 moreInternal Medicine, Hypertension, Blood Pressure, Aldosterone, Female, Drug Resistance, Male, Clinical Sciences, Aged, Adult, Drug Therapy, Captopril, Cohort Studies, Antihypertensive agents, and Cardiovascular medicine and haematology
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Nowadays, an urgent need for global medical cooperation and assistance still bears on health care providers. Because plastic, reconstructive, and aesthetic surgery is a surgical specialty with social purposes, the humanitarian importance... more
Nowadays, an urgent need for global medical cooperation and assistance still bears on health care providers. Because plastic, reconstructive, and aesthetic surgery is a surgical specialty with social purposes, the humanitarian importance of the discipline is, nowadays, stronger than ever. Padova Hospitale Onlus is a nonprofit charity association with the aim to ensure sustainable medical programs, in particular in the field of plastic and reconstructive surgery. The activity of the association in fund-raising strategies, volunteer enrollment, and operative strategies has been reviewed and reported to stimulate further collaboration, emulation, and contributions. Since 1996, the association has assisted over 20,000 people during 50 missions over the 5 continents, performing more than 2000 surgical operations and almost 8000 medical examination, involving more than 320 volunteers, supplying health care material or health care facilities. Furthermore, a high rate of surgical records and of medical assistance has been performed in the last 2 years, depicting a positive rising trend of activity. However, scarce financial means, absence of a structured coordination, and/or cooperation between associations may often affect the long-term sustainability of these interventions. Thus, only an experienced and structured association may grant the required resources to sustain adequate and fruitful short-term or long-term projects for the promotion of a humanitarian cooperation as much "demand driven" as possible.
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The aim of this 3-month, double-blind, double-dummy, parallel group study was to compare the antihypertensive efficacy and acceptability of perindopril (4-8 mg/day) in 54 patients (30 males, 24 females, 25-68 years of age) and captopril... more
The aim of this 3-month, double-blind, double-dummy, parallel group study was to compare the antihypertensive efficacy and acceptability of perindopril (4-8 mg/day) in 54 patients (30 males, 24 females, 25-68 years of age) and captopril (50-100 mg/day) in 54 patients (39 males, 15 females, 29-66 years of age) in the treatment of essential hypertension. In a subgroup of 38 patients a complete echocardiographic study was performed. The two groups had similar (ANOVA) blood pressure (BP), heart rate (HR), body mass index, and duration of hypertension. Supine and standing BP was significantly reduced by both drugs, without differences between them. Owing to poor control of BP, hydrochlorothiazide (25 mg/day) was added to 27% of patients on perindopril and to 41% of patients on captopril (p less than 0.05). Normalization of supine diastolic BP (less than or equal to 90 mm Hg) was obtained in 67% of patients on perindopril and in 47% of patients on captopril (p less than 0.01). No change in HR was detected. Only mild untoward effects were recorded. Left ventricular mass was significantly reduced by either drug, with no change in systolic function. In conclusion, perindopril and captopril, at these doses, were both well tolerated and on average reduced BP to a similar extent; however, treatment with perindopril showed that fewer patients needed the addition of a thiazide and BP became normal in a larger number of patients.