Giuliana Properzi

Circulating endothelin-1 levels increase during euglycemic hyperinsulinemic clamp in lean NIDDM men.

OBJECTIVE To evaluate whether or not insulin stimulates endothelin (ET)-l secretion in vivo. RESEARCH DESIGN AND METHODS Plasma ET-1 levels were evaluated in 16 lean normotensive men with non-insulin-dependent diabetes mellitus (NIDDM) (mean age 50.3 ±4.1 years) during either a 2-h euglycemic hyperinsulinemic clamp (40 mU insulin · m−2 · min−1) or placebo infusion (50 ml isotonic saline) according to a single-blind randomized crossover protocol. RESULTS Circulating ET-1 levels increased during the euglycemic hyperinsulinemic clamp (from 0.88 ± 0.38 pg/ml at time 0 to 1.66 ± 0.22 pg/ml and 1.89 ± 0.99 pg/ml at 60 and 120 min, respectively [P < 0.05 vs. time 0]) and returned to baseline levels after the discontinuation of insulin infusion (0.71 ± 0.22 pg/ml after a 30-min period of recovery [NS]). Compared with placebo, the euglycemic hyperinsulinemic clamp induced a significant increase in plasma ET-1 levels at 60 min (P < 0.0001) and 120 min (P < 0.0001). Changes in basal insulin levels and corresponding changes in circulating ET-1 levels after a 2-h euglycemic hyperinsulinemic clamp were significantly correlated (r = 0.771, P < 0.0001). A possible unfavorable effect of ET-1 on the tissue sensitivity to insulin-stimulated glucose uptake was suggested by the presence of a negative correlation between total glucose uptake and baseline ET-1 levels (r = –0.498, P < 0.05). CONCLUSIONS Our findings indicate that circulating ET-1 levels significantly increase during euglycemic hyperinsulinemic clamp in men with NIDDM. The negative correlation between total glucose uptake and circulating ET-1 levels suggests that the peptide might exert negative effects on the insulin sensitivity of target tissues. The consequent increase in insulin secretion as well as the insulin-related ET-1 release from endothelial cells could favor the development of diabetes-related vascular lesions.

Chronic Hyperuricemia, Uric Acid Deposit and Cardiovascular Risk

Hyperuricemia is commonly associated with traditional risk factors such as dysglicemia, dyslipidemia, central obesity and abnormal blood pressure, i.e. the metabolic syndrome. Concordantly, recent studies have revived the controversy over the role of circulating uric acid, hyperuricemia, and gout as an independent prognostic factor for cardiovascular morbidity and mortality. In this regard, different studies also evaluated the possible role of xanthine inhibitors in inducing blood pressure reduction, increment in flow-mediated dilation, and improved cardiovascular prognosis in various patient settings. The vast majority of these studies have been conducted with either allopurinol or its active metabolite oxypurinol, i.e. two purine-like non-selective inhibitors of xanthine oxidase. More recently, the role of uric acid as a risk factor for cardiovascular disease and the possible protective role exerted by reduction of hyperuricemia to normal level have been evaluated by the use of febuxostat, a selective, non purine-like xanthine oxidase inhibitor. In this review, we will report current evidence on hyperuricemia in cardiovascular disease. The value of uric acid as a biomarker and as a potential therapeutic target for tailored old and novel “cardiometabolic” treatments will be also discussed.

ENDOTHELIN-1 IN DIABETIC AND NONDIABETIC MEN WITH ERECTILE DYSFUNCTION

PURPOSE We evaluated plasma concentration of endothelin-1 in diabetic and nondiabetic men complaining of erectile dysfunction, and the variation of endothelin-1 in cavernous body blood during intracavernous injection of prostaglandin E1. MATERIALS AND METHODS We evaluated plasma concentrations of endothelin-1 in venous blood of 20 men with erectile dysfunction, 10 with and 10 without diabetes. Plasma concentration of endothelin-1 was also evaluated in the cavernous body blood of the 20 men with erectile dysfunction, during erection induced by intracavernous injection of 10 micrograms prostaglandin E1. A severe vasculogenic component of erectile dysfunction was excluded in all patients. RESULTS Basal plasma concentration of endothelin-1 in the cubital vein was increased in nondiabetic (1.13 +/- 0.4 pg./ml.) and in diabetic (1.80 +/- 0.2 pg./ml.) patients with erectile dysfunction, compared to control men (0.64 +/- 0.1 pg./ml.) (p < 0.0005 and p < 0.0001, respectively), and in diabetic compared with nondiabetic patients (p < 0.002). No difference and close correlation were observed in the concentration of endothelin-1 in the cavernous body blood evaluated 5 minutes and 30 minutes after injection of prostaglandin E1 (r = 0.89, p < 0.0001, y = 0.98 x + -0.066). The concentration of endothelin-1 in the cavernous body blood evaluated 30 minutes after injection of prostaglandin E1 did not show any difference compared to peripheral venous concentration of the peptide in the 2 patient groups. Concentrations of endothelin-1 in the peripheral vein and the cavernous body blood were not different in patients with a full erection compared with incomplete penis erection after injection of prostaglandin E1 in the cavernous body.

Vitamin D Protects Human Endothelial Cells from H2O2 Oxidant Injury Through the Mek/Erk-Sirt1 Axis Activation

Endothelium homeostasis alterations govern the pathogenesis of cardiovascular diseases. Several studies show that vitamins anti-oxidant proprieties rescue the endothelial functions adversely affected by oxidative stress in several diseases. We investigated the vitamin D anti-oxidant potential in human endothelial cells exposed to H2O2 oxidative stress. Vitamin D protected endothelial cells against H2O2 oxidative stress counteracting the superoxide anion generation, the apoptosis and blocking the extrinsic caspase cascade by positively controlling phospho-active ERKs level. MEKs/ERKs inhibitor U0126 reverted the vitamin D anti-oxidant effects. Characterizing the vitamin D downstream effector, we found that vitamin D up-regulated SirT-1 and reverted the SirT-1 down-regulation induced by H2O2. ERKs activation by vitamin D strictly correlated with SirT-1 protein accumulation since both MEKs/ERKs inhibition and ERK1/2 silencing decreased SIRT-1. SirT-1 inhibition by Sirtinol reverted the vitamin D anti-oxidant effects. Thus, vitamin D significantly reduced the endothelial malfunction and damage caused by oxidative stress, through the activation of MEKs/ERKs/SirT-1 axis.

Postnatal development and distribution of peptide-containing nerves in the genital system of the male rat

SummaryThe distribution and relative density of peptide-containing nerves was studied in the rat in order to assess the progression of neuronal changes during the postnatal development of the male genital system from the prepubertal age to adulthood. Testis, caput and cauda epididymis, ductus deferens, seminal vescicles, prostate and penis from 8-, 20-, 38-, and 70-day-old rats were sectioned and were immunostained with antisera to the neuropeptides calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), and to a general neuronal marker, protein gene product 9.5 (PGP 9.5). The testicular parenchyma and caput epididymis did not show any immunoreactivity. Very scattered CGRP-containing nerves were present in 8-day-old rats; numerous VIP-, CGRP-, and NPY-peptide-containing nerves were observed in the cauda epididymis, ductus deferens, accessory glands and penis of 20-day-old rats. The number of nerves increased in 35-day-old rats while no changes were observed in more adult rats. A parallel increase was seen for the immunostain for PGP 9.5. These data suggest that peptide-containing nerves appear in the genital system after birth and reach a full development before the completion of puberty. Peptide-containing nerves were visible first in the interstitial area and then spread in the muscular coat of the ducts, glands and of the blood vessels. While CGRP- and NPY-containing nerves were distributed in the vicinity of the muscle cells, VIP-containing nerves were also observed in the subepithelial regions, suggesting a possible role of this neuropeptide in the control of epithelial functions.

Circulating endothelin-1 levels in lean non-insulin-dependent diabetic patients: Influence of ACE inhibition

To evaluate the effect of captopril on plasma endothelin-1 (ET-1) levels and insulin sensitivity, 15 lean normotensive men (51.6 +/- 3.8 years) affected by non-insulin-dependent diabetes mellitus (NIDDM) underwent 2-h euglycemic hyperinsulinemic clamp. Each patient was then assigned to receive either captopril (25 mg twice daily for 1 week) or placebo, in a double-blind randomized fashion, before repeating clamp. At baseline, plasma ET-1 levels were 0.77 +/- 0.25 pg/mL in captopril (n = 10) and 0.83 +/- 0.3 pg/mL in placebo patients (n = 5). A twofold increase in plasma ET-1 levels occurred during the 2-h insulin infusion in both groups (P < .05 after 60 and 120 min), with a rapid return to baseline after 30 min from insulin withdrawal. After 1 week of therapy, total glucose uptake significantly increased in captopril (from 3.71 +/- 1.70 mg/kg/min to 4.24 +/- 1.72 mg/kg/min, P < .03) but not in placebo patients. Plasma ET-1 levels significantly decreased after captopril therapy (0.48 +/- 0.25 pg/mL at time 0, P < .03 v pretreatment levels), but were unaffected by placebo. Moreover, captopril slightly reduced the magnitude of ET-1 increment during insulin infusion (0.65 +/- 0.28 pg/mL and 0.88 +/- 0.48 pg/mL at 60 and 120 min, respectively, P < .05 v time 0). As a consequence, during the second insulin infusion circulating ET-1 levels were significantly lower in captopril- than in placebo-treated patients at time 0 (P < .02), 60 (P < .002), 120 (P < .004), and 150 min (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Serum uric acid levels and metabolic syndrome

Abstract Objective: To investigate the relationship among serum uric acid levels and metabolic syndrome. Materials and methods: Anthropometric parameters, serum uric acid and metabolic parameters were evaluated in 139 subjects. Results: Serum uric acid levels were significantly higher in subjects with than without metabolic syndrome (p < 0.0001), and raised gradually with the increasing number of metabolic syndrome components (p for trend < 0.0001). Serum uric acid significantly correlated with various anthropometric and serum metabolic parameters. Discussion and conclusions: Serum uric acid levels were higher in individuals with rather than without metabolic syndrome and raised gradually as the number of metabolic syndrome components increased. The relationship between serum uric acid levels and various metabolic parameters suggests that uric acid might be considered as a component of metabolic syndrome. Context: Hyperuricemia is a common finding in patients with the metabolic syndrome. Recent studies indicated that hyperuricemia may be also a predictor of metabolic syndrome development.

Occurrence of the Interference of Sperm-Associated Antibodies on Sperm Fertilizing Ability as Evaluated by the Sperm-Zona Pellucida Binding Test and by the TEST-Yolk Buffer Enhanced Sperm Penetration Assay

PROBLEM: This study was performed to evaluate the occurrence as well as the level of the interference of sperm‐associated antibodies on fertilization process.

Long-term blood pressure changes induced by the 2009 L’Aquila earthquake: assessment by 24h ambulatory monitoring

An increased rate of cardiovascular and cerebrovascular events has been described during and immediately after earthquakes. In this regard, few data are available on long-term blood pressure control in hypertensive outpatients after an earthquake. We evaluated the long-term effects of the April 2009 L’Aquila earthquake on blood pressure levels, as detected by 24 h ambulatory blood pressure monitoring. Before/after (mean±s.d. 6.9±4.5/14.2±5.1 months, respectively) the earthquake, the available 24 h ambulatory blood pressure monitoring data for the same patients were extracted from our database. Quake-related daily life discomforts were evaluated through interviews. We enrolled 47 patients (25 female, age 52±14 years), divided into three groups according to antihypertensive therapy changes after versus before the earthquake: unchanged therapy (n=24), increased therapy (n=17) and reduced therapy (n=6). Compared with before the quake, in the unchanged therapy group marked increases in 24 h (P=0.004), daytime (P=0.01) and nighttime (P=0.02) systolic blood pressure were observed after the quake. Corresponding changes in 24 h (P=0.005), daytime (P=0.01) and nighttime (P=0.009) diastolic blood pressure were observed. Daily life discomforts were reported more frequently in the unchanged therapy and increased therapy groups than the reduced therapy group (P=0.025 and P=0.018, respectively). In conclusion, this study shows that patients with unchanged therapy display marked blood pressure increments up to more than 1 year after an earthquake, as well as long-term quake-related discomfort. Our data suggest that particular attention to blood pressure levels and adequate therapy modifications should be considered after an earthquake, not only early after the event but also months later.

Platelet activation in patients with the Raynaud phenomenon

Background:  The Raynaud phenomenon (RP) is an exaggerated and reversible vasospasm of small arteries triggered by cold or emotional stress. Primary RP (PRP) term is used when the underlying condition is unknown. An altered regulation in vascular tone and/or release of soluble mediators from activated platelets plays a role in PRP through an increased oxidative stress. We assessed platelet activation and oxidative stress in patients with PRP by measuring platelet PAC‐1, an index of glycoprotein (Gp) IIb/IIIa receptor activation, thromboxane A2 (TXA2), an index of platelet activation and 8‐epi‐prostaglandin F2α (8‐epi‐PGF2α), a marker of endogenous in vivo peroxidation.