Bartolomeo Farzati

Bio: Bartolomeo Farzati is an academic researcher from University of Naples Federico II. The author has contributed to research in topics: Progenitor cell & Angiogenesis. The author has an hindex of 17, co-authored 23 publications receiving 1245 citations. Previous affiliations of Bartolomeo Farzati include Seconda Università degli Studi di Napoli.

Impairment of Endothelial Functions by Acute Hyperhomocysteinemia and Reversal by Antioxidant Vitamins

Abstract: ContextIncreased levels of homocysteine are associated with risk of cardiovascular disease. Homocysteine may cause this risk by impairing endothelial cell function.ObjectiveTo evaluate the effect of acute hyperhomocysteinemia with and without antioxidant vitamin pretreatment on cardiovascular risk factors and endothelial functions.Design and SettingObserver-blinded, randomized crossover study conducted at a university hospital in Italy.SubjectsTwenty healthy hospital staff volunteers (10 men, 10 women) aged 25 to 45 years.InterventionsSubjects were given each of 3 loads in random order at 1-week intervals: oral methionine, 100 mg/kg in fruit juice; the same methionine load immediately following ingestion of antioxidant vitamin E, 800 IU, and ascorbic acid, 1000 mg; and methionine-free fruit juice (placebo). Ten of the 20 subjects also ingested a placebo load with vitamins.Main Outcome MeasuresLipid, coagulation, glucose, and circulating adhesion molecule parameters, blood pressure, and endothelial functions as assessed by hemodynamic and rheologic responses to L-arginine, evaluated at baseline and 4 hours following ingestion of the loads.ResultsThe oral methionine load increased mean (SD) plasma homocysteine level from 10.5 (3.8) µmol/L at baseline to 27.1 (6.7) µmol/L at 4 hours (P<.001). A similar increase was observed with the same load plus vitamins (10.0 [4.0] to 22.7 [7.8] µmol/L; P<.001) but no significant increase was observed with placebo (10.1 [3.7] to 10.4 [3.2] µmol/L; P=.75). Coagulation and circulating adhesion molecule levels significantly increased after methionine ingestion alone (P<.05) but not after placebo or methionine ingestion with vitamins. While the mean (SD) blood pressure (−7.0% [2.7%]; P<.001), platelet aggregation response to adenosine diphosphate (−11.4% [4.5%]; P=.009) and blood viscosity (−3.0% [1.2%]; P=.04) declined in these parameters 10 minutes after an L-arginine load (3 g) following placebo, the increase after methionine alone (−2.3% [1.5%], 4.0% [3.0%], and 1.5% [1.0%], respectively; P<.05), did not occur following methionine load with vitamin pretreatment (−6.3% [2.5%], −7.9% [3.5%], and −1.5% [1.0%], respectively; P=.24).ConclusionOur data suggest that mild to moderate elevations of plasma homocysteine levels in healthy subjects activate coagulation, modify the adhesive properties of endothelium, and impair the vascular responses to L-arginine. Pretreatment with antioxidant vitamin E and ascorbic acid blocks the effects of hyperhomocysteinemia, suggesting an oxidative mechanism.

Circulating adhesion molecules in humans: role of hyperglycemia and hyperinsulinemia.

Abstract: Background—We assessed the role of glucose and insulin in the regulation of circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular adhesion molecule-1 (sVCAM-1) in normal subjects and in patients with type 2 diabetes. Methods and Results—Plasma glucose concentrations were acutely raised in 10 normal subjects and 10 newly diagnosed, complication-free type 2 diabetic patients and maintained at 15 mmol/L for 2 hours. In normal subjects, plasma sICAM-1, but not sVCAM-1, levels rose significantly (P<0.01) at 1 hour and returned to basal values at 2 hours. In another study, octreotide was infused during the hyperglycemic clamp to block the release of endogenous insulin; this prevented the late fall of plasma sICAM-l levels observed in under control clamp conditions. The diabetic patients had plasma sICAM-1 levels significantly higher (P<0.01) than those of the control subjects; plasma sVCAM-1 levels were similar. Both sICAM-l and sVCAM-1 concentrations did not change significantl...

Beneficial effects of concurrent autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the mouse hindlimb.

Abstract: Lower-limb ischemia is a major health problem. Because of the absence of effective treatment in the advanced stages of the disease, amputation is undertaken to alleviate unbearable symptoms. Novel therapeutic approaches include the intramuscular use of autologous bone marrow cells (BMCs). Because tissue ischemia is associated with an overwhelming generation of oxygen radicals and negative effects due to perturbed shear-stress, metabolic intervention with antioxidants and l-arginine could potentially induce beneficial effects beyond those achieved by BMCs. The protective effect of autologous BMCs and vascular protection by metabolic cotreatment (1.0% vitamin E added to the chow and 0.05% vitamin C and 6% l-arginine added to the drinking water) were examined in ischemia-induced angiogenesis in the mouse hindlimb, a model of extensive acute peripheral arterial occlusion. i.v. BMC therapy improved blood flow and increased capillary densities and expression of Ki-67, a proliferation-associated protein. This beneficial effect was amplified by metabolic cotreatment, an intervention inducing vascular protection, at least in part, through the nitric oxide pathway, reduction of systemic oxidative stress, and macrophage activation. Therefore, although a cautious approach is mandatory when experimental findings are extended to human diseases, autologous BMCs together with metabolic intervention could be an effective clinical treatment for peripheral arterial disease.

Type-1 response in peripheral CD4+ and CD8+ T cells from patients with Hashimoto's thyroiditis.

Abstract: Objective: In this study we performed single-cell analysis of the intracellular cytokine expression in peripheral CD4 + and CD8 + lymphocytes from patients with Hashimoto’s thyroiditis (HT) to investigate the type-1 response separately for the two lymphocyte sub-populations. Design and methods: Twenty-nine patients affected by HT and 20 healthy subjects, matched for sex and age, were enrolled. After the analysis of the lymphocyte sub-populations, the intracellular content of interferon-g (IFN-g) in phorbolmyristate acetate (PMA)-stimulated CD4 + and CD8 + lymphocytes was assayed. Moreover, the CD4 + lymphocytes were also evaluated for the intracellular expression of IL-4. Results: No significant differences in CD3 + , CD4 + and CD8 + lymphocytes were found between HT patients and control subjects. However, the HT patients showed higher numbers of CD4 + IFN-g + , CD4 + IL-4 + and CD8 + IFN-g + ðt-test; P # 0:001Þ cells than the control subjects. Analysing the intracellular expression of IFN-g and IL-4 in relation to thyroid function, we found that the euthyroid patients (18 cases) showed more expression of IL-4 in CD4 + lymphocytes than the control subjects, without any significant modification of IFN-g expression in CD4 + and CD8 + lymphocytes. However, the hypothyroid patients (11 cases) showed an increase of IFN-g expression in both CD4 + and CD8 + lymphocytes with respect to the control subjects and the euthyroid patients. Moreover, the expression of IL-4 in CD4 + cells from hypothyroid patients was significantly lower than that seen in the euthyroid cases and comparable to that found in the control subjects. Conclusions: Our study has demonstrated that the peripheral CD4 + and CD8 + T lymphocytes from the HT patients show a type-1 activation strictly correlated to the occurrence of hypothyroidism. Further studies will be needed to clarify the exact role of peripheral lymphocytes in HT and whether they could provide a reliable marker of thyroid immune involvement.

Reduction of Inflammatory Cytokine Concentrations and Improvement of Endothelial Functions in Obese Women After Weight Loss Over One Year

Abstract: Background— Visceral fat is a key regulator site for the process of inflammation, and atherosclerotic lesions are essentially an inflammatory response. Methods and Results— Fifty-six healthy premenopausal obese women (age range 25 to 44 years, body mass index 37.2±2.2, waist to hip ratio range 0.78 to 0.92) and 40 age-matched normal weight women were studied. Compared with nonobese women, obese women had increased basal concentrations of tumor necrosis factor-α (TNF-α, P<0.01), interleukin-6 (IL-6, P<0.01), P-selectin (P<0.01), intercellular adhesion molecule-1 (ICAM-1, P<0.02), and vascular adhesion molecule-1 (VCAM-1, P<0.05). Vascular responses to l-arginine (3 g IV), the natural precursor of nitric oxide, were impaired in obese women: reductions in mean blood pressure (P<0.02), platelet aggregation to adenosine diphosphate (P<0.05), and blood viscosity (P<0.05) were significantly lower as compared with those in the nonobese group. Concentrations of TNF-α and IL-6 were related (P<0.01) to visceral obes...

Postprandial Hyperglycemia and Diabetes Complications Is It Time to Treat

Abstract: Increasing evidence suggests that the postprandial state is a contributing factor to the development of atherosclerosis. In diabetes, the postprandial phase is characterized by a rapid and large increase in blood glucose levels, and the possibility that the postprandial "hyperglycemic spikes" may be relevant to the onset of cardiovascular complications has recently received much attention. Epidemiological studies and preliminary intervention studies have shown that postprandial hyperglycemia is a direct and independent risk factor for cardiovascular disease (CVD). Most of the cardiovascular risk factors are modified in the postprandial phase in diabetic subjects and directly affected by an acute increase of glycemia. The mechanisms through which acute hyperglycemia exerts its effects may be identified in the production of free radicals. This alarmingly suggestive body of evidence for a harmful effect of postprandial hyperglycemia on diabetes complications has been sufficient to influence guidelines from key professional scientific societies. Correcting the postprandial hyperglycemia may form part of the strategy for the prevention and management of CVDs in diabetes.

Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial.

Abstract: ContextHealthy lifestyle factors are associated with maintenance of erectile function in men.ObjectiveTo determine the effect of weight loss and increased physical activity on erectile and endothelial functions in obese men.Design, Setting, and PatientsRandomized, single-blind trial of 110 obese men (body mass index ≥30) aged 35 to 55 years, without diabetes, hypertension, or hyperlipidemia, who had erectile dysfunction that was determined by having a score of 21 or less on the International Index of Erectile Function (IIEF). The study was conducted from October 2000 to October 2003 at a university hospital in Italy.InterventionsThe 55 men randomly assigned to the intervention group received detailed advice about how to achieve a loss of 10% or more in their total body weight by reducing caloric intake and increasing their level of physical activity. Men in the control group (n = 55) were given general information about healthy food choices and exercise.Main Outcomes MeasuresErectile function score, levels of cholesterol and tryglycerides, circulating levels of interleukin 6, interleukin 8, and C-reactive protein, and endothelial function as assessed by vascular responses to L-arginine.ResultsAfter 2 years, body mass index decreased more in the intervention group (from a mean [SD] of 36.9 [2.5] to 31.2 [2.1]) than in the control group (from 36.4 [2.3] to 35.7 [2.5]) (P<.001), as did serum concentrations of interleukin 6 (P = .03), and C-reactive protein (P = .02). The mean (SD) level of physical activity increased more in the intervention group (from 48 [10] to 195 [36] min/wk; P<.001) than in the control group (from 51 [9] to 84 [28] min/wk; P<.001). The mean (SD) IIEF score improved in the intervention group (from 13.9 [4.0] to 17 [5]; P<.001), but remained stable in the control group (from 13.5 [4.0] to 13.6 [4.1]; P = .89). Seventeen men in the intervention group and 3 in the control group (P = .001) reported an IIEF score of 22 or higher. In multivariate analyses, changes in body mass index (P = .02), physical activity (P = .02), and C-reactive protein (P = .03) were independently associated with changes in IIEF score.ConclusionLifestyle changes are associated with improvement in sexual function in about one third of obese men with erectile dysfunction at baseline.

Tight Glycemic Control in Diabetic Coronary Artery Bypass Graft Patients Improves Perioperative Outcomes and Decreases Recurrent Ischemic Events

Abstract: Background— This study sought to determine whether tight glycemic control with a modified glucose-insulin-potassium (GIK) solution in diabetic coronary artery bypass graft (CABG) patients would imp...