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Biomedical subjects

Franco Cuccurullo

Publications and source records attributed to Franco Cuccurullo.

44 records · Page 3Linked to original sources

Vanadyl as a catalyst of human lipoprotein oxidation.

Lipoprotein oxidation, which is relevant to atherogenesis, can be induced by redox-active transition metals, such as copper. Vanadium is a metal usually used as vanadyl to improve metabolic control in diabetic patients; given its redox-active properties, we have investigated possible oxidative effects of the metal on lipoproteins from healthy and diabetic subjects. Beginning from 10 microM, vanadyl, but not vanadate, induced oxidation of the non-HDL fraction, which was inhibited by EDTA, butylated hydroxytoluene and Vitamins E and C, but not by mannitol, SOD and catalase. Differently from copper, vanadyl could oxidize directly lipoprotein lipids, although it showed a lower oxidant activity against critical tryptophan residues of the lipoprotein protein moiety. Moreover, the non-HDL fraction of diabetic patients was more susceptible to vanadyl-dependent oxidation than that of controls. Thus, vanadium, in its reduced form which may be used in humans, can oxidize the non-HDL fraction through oxidative effects exerted especially on lipoprotein lipids; the specific pro-oxidant activity of vanadyl is more evident with lipoproteins of diabetic patients. Given also the tissue accumulating capacity of vanadium conceivably in a reduced form, its prolonged administration to humans, especially to diabetic patients without adequate antioxidant supplementation, needs caution.

Apolipoproteins B↗

Association of factor VII levels with inflammatory parameters in hypercholesterolemic patients.

Inflammatory markers have been demonstrated to be associated with increased risk of cardiovascular events. In this setting, C-reactive protein (CRP) was shown to add predictive value to cholesterol levels. We investigated hypercholesterolemic patients and related their inflammatory variables and their coagulation state focusing on factor VII, a coagulation protein which plays an established role in thrombogenesis. We examined the relationship between factor VII clotting activity (FVIIc), FVII antigen (FVIIAg) and activated FVII (FVIIa) levels against CRP, interleukin-6 soluble receptor (IL-6sR), P-selectin, soluble intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-beta(1) (TGF-beta(1)), in fifty-eight hypercholesterolemic subjects. Patients were subjected to 6-8 weeks of lipid lowering treatment with diet or diet plus pravastatin (40 mg/day). Univariate analysis showed that FVII levels were positively associated with CRP (FVIIAg: r=0.56, P<0.0001; FVIIc: r=0.57, P<0.0001; FVIIa: r=0.39, P<0.001) and IL-6sR (FVIIAg: r=0.59, P<0.0001; FVIIc: r=0.52, P<0.0001; FVIIa: r=0.47; P<0.001). CRP was still correlated, at the baseline, with FVIIAg and FVIIc levels after multiple stepwise regression analysis (FVIIAg: P<0.0001; FVIIc: P<0.0001, respectively) and with FVIIAg at the end of lipid lowering treatment (P<0.0001). Our data indicate that the FVII level is independently associated with inflammatory variables and suggest their pathophysiological link in hypercholesterolemic patients.

Adult↗

Transforming growth factor-beta1 levels in hypertensive patients: association with body mass index and leptin.

BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) has been demonstrated to be overexpressed in hypertension. Leptin, an adipocyte product, has been shown to play a role in obesity-related hypertension and in vitro studies demonstrated a biologic interaction between leptin and TGF-beta1. Thus, we evaluate a possible in vivo association between TGF-beta1, body mass index (BMI), and leptin circulating levels in hypertensive subjects. METHODS: Blood samples for fasting leptin and TGF-beta1, were evaluated in 29 overweight, 46 obese, and 29 nonobese hypertensive patients before and after a 12-week calorie-restricted diet. Monocyte cultures were used for in vitro experiments. RESULTS: Transforming growth factor-beta1 was significantly elevated in hypertensive obese patients (n = 46) as compared with TGF-beta1 levels of hypertensive patients with normal BMI (n = 29) (8. 9 +/- 3 ng/mL v 4.4 +/- 2; P < .001). The circulating levels of TGF-beta1 were associated with BMI and leptin levels in an univariate analysis (r = 0.59, P < .0001; r = 0.62, P < .0001, respectively) and these associations were still present after stepwise multivariate analysis. Weight loss of 10% produced a parallel decrease in TGF-beta1 (from 8.9 +/- 3 ng/mL to 5.3 +/- 2.8 ng/mL; P < .01) and leptin levels (from 30 +/- 24 ng/mL to 17 +/- 14; P < .05). In vitro experiments showed that leptin is able to induce a dose-dependent increase in TGF-beta1 production and mRNA expression in human monocyte cultures. CONCLUSIONS: Our data indicate that TGF-beta1 levels are positively associated with BMI and leptin levels in hypertensive patients and suggest that adipose tissue may be an important determinant of TGF-beta1 levels possibly by a leptin-dependent pathway.

Adult↗

Endothelial function in sustained and white coat hypertension.

BACKGROUND: Endothelial dysfunction is a frequent finding in essential hypertension. The aim of this study was to assess endothelial function, by evaluating circulating nitric oxide metabolites, nitrate plus nitrite (NOx), and endothelium-dependent vasodilation (EDD), in white coat hypertension in comparison with sustained hypertension and normotension. METHODS: We selected 22 sustained hypertensive, 22 white coat hypertensive, and 22 normotensive subjects matched for age, gender, body mass index, and occupation. Women were also matched for menopausal status. Subjects with smoking habit, dyslipidemia, and diabetes mellitus were excluded from the study. White coat hypertension was defined as clinical hypertension and daytime ambulatory blood pressure (BP) <135/85 mm Hg. Groups received for 2 days a low-nitrate diet before obtaining blood samples for laboratory measurements. The NOx levels were measured by using the Griess reagent after enzymatic conversion of all nitrate to nitrite. Subjects also underwent brachial artery study by ultrasonography to evaluate EDD and endothelium-independent vasodilation. RESULTS: White coat hypertensive subjects had significantly higher levels of NOx than sustained hypertensive patients (30.8 +/- 12 v 22 +/- 8.5 micromol/L, P <.05) and significantly higher EDD (7.8% +/- 3.1% v 4.6% +/- 3.0%, P <.05). No significant difference was observed between white coat hypertensive and normotensive subjects regarding these parameters. Endothelium-independent vasodilation was not significantly different among sustained hypertensives, white coat hypertensives, and normotensives (18% +/- 4.2% v 18.3% +/- 3.9% v 18.6% +/- 4.8%, respectively, P = not significant). CONCLUSIONS: Our data suggest that middle-aged white coat hypertensive subjects without other cardiovascular risk factors do not show endothelial dysfunction in contrast with sustained hypertensive patients.

Adult↗

Heart rate in hypertensive patients treated with ACE inhibitors and long-acting dihydropyridine calcium antagonists.

Rapid heart rate (HR) has been reported to be a predictor of cardiovascular morbidity and mortality in hypertensive patients. The aim of this study was to evaluate the effect of ACE inhibitors and long-acting dihydropyridine calcium antagonists on clinic and ambulatory HR in patients with essential hypertension. We selected 292 hypertensive patients treated with ACE inhibitors and 198 hypertensive patients treated with dihydropyridine calcium antagonists. Groups were balanced for age, gender, body mass index, baseline blood pressure (BP) and HR, treatment duration and occupation. Patients had been submitted to clinic evaluation and noninvasive monitoring of BP and HR at baseline and during chronic therapy. Clinic and ambulatory BP were significantly and similarly reduced in patients treated with ACE inhibitors and calcium antagonists. Globally, clinic and 24-h HR were significantly reduced in patients treated with ACE inhibitors and remained unchanged in those treated with calcium antagonists. When patients were grouped according to baseline clinic HR (< 65 beats/min, 65-74 beats/min, 75-84 beats/min, and >85 beats/min), ACE inhibitors did not significantly change HR in subjects with baseline clinic HR <74 beats/min but significantly reduced clinic, 24-h, daytime and nighttime HR in those with baseline HR >75 beats/min and particularly in those with baseline HR >85 beats/min. Calcium antagonists did not significantly change clinic, 24-h, daytime and nighttime HR in various subgroups. Our study shows that ACE inhibitors reduce both clinic and ambulatory HR in hypertensive patients with faster HR, who seem to be at higher risk, and that long-acting dihydropyridine calcium antagonists do not induce significant changes in HR during chronic treatment (neither decrease nor increase). Whether this aspect is associated with a better prognostic impact of ACE inhibitors in essential hypertension should be determined in prospective studies.

Angiotensin-Converting Enzyme Inhibitors↗

Circulating monocyte chemoattractant protein-1 and early development of nephropathy in type 1 diabetes.

OBJECTIVES: To investigate the possible role of hyperglycemia-dependent monocyte chemoattractant protein (MCP)-1 biosynthesis in the pathophysiology of early nephropathy in type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied 30 patients with type 1 diabetes (15 with and 15 without microalbuminuria) compared with matched healthy control subjects. Plasma MCP-1 and plasma oxidant status (vitamin E, fluorescent products of lipid peroxidation [FPLPs], malondialdehyde [MDA]), HbA(1c), and albumin excretion rate [AER]) were evaluated at baseline. Furthermore, MCP-1, vitamin E, AER, and HbA(1c) were also analyzed in the microalbuminuric diabetic patients and in the healthy volunteers after 8 weeks of high-dose (600 mg b.i.d.) vitamin E treatment. RESULTS: FPLPs, MDA, and MCP-1 were significantly higher, whereas vitamin E was significantly lower in patients with microalbuminuria and poorer glycemic control as compared with normoalbuminuric patients and healthy control subjects. Plasma MCP-1 was positively correlated with HbA(1c), FPLPs, MDA, and AER, whereas plasma MCP-1 showed an inverse correlation with vitamin E. Interestingly, both MCP-1 and AER decreased significantly after vitamin E treatment, despite no changes in HbA(1c) values. CONCLUSIONS: This study suggests that prolonged hyperglycemia may lead to early renal complications in type 1 diabetes by inducing MCP-1 biosynthesis via enhanced oxidative stress. Long-term treatment of high-dose vitamin E significantly decreased MCP-1, thus providing a rationale basis for evaluating vitamin E supplementation as therapy adjuvant to conventional insulin treatment in type 1 diabetic patients in whom an acceptable glycemic control is difficult to achieve despite appropriate insulin treatment.

Adult↗

New method for the extraction of DNA from white blood cells for the detection of common genetic variants associated with thrombophilia.

In the last few years, FV Leiden, prothrombin 20210 and thermolabile methylene tetrahydrofolate reductase (MTHFR) 677 variants have been identified as possible risk factors associated with thrombophilia, and many PCR-based methods have been described for detecting these variations. However, the genomic DNA extraction is still a rate-limiting and time-consuming step in the PCR process. In an attempt to accelerate this procedure and make it suitable for routine laboratory, we report a single preparative technique for DNA extraction from peripheral blood samples using an anion-binding resin (GeneFizz). This method enables white blood cell lysis, DNA extraction and PCR amplification directly in the thermocycling tube on the thermocycler. The use of this new DNA extraction system coupled to a multiplex PCR allows rapid genetic screening of large cohorts of patients for thrombophilic risk factors.

Anion Exchange Resins↗