Biomedical subjects

Vincenzo Sica

Publications and source records attributed to Vincenzo Sica.

At least 19 recordsLinked to original sources

PubMed2006

Autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the diabetic mouse hindlimb.

Peripheral arterial disease (PAD) is a major health problem especially when associated to diabetes. Administration of autologous bone marrow cells (BMC) is emerging as a novel intervention to induce therapeutic angiogenesis in experimental ischemic limb models and in patients with PAD. Since tissue ischemia and diabetes are associated with an overwhelming generation of oxygen radicals and detrimental effects due to formation of glycosylation end-products, metabolic intervention with antioxidants and L-arginine can confer beneficial effects beyond those achieved by BMC alone. The effects of cotreatment with intravenous BMCs and metabolic vascular protection (1.0% vitamin E, 0.05% vitamin C, and 6% L-arginine) were examined in the ischemic hindlimb of diabetic and non diabetic mice. BMC therapy increased blood flow and capillary densities and Ki67 proliferative marker, and decreased interstitial fibrosis. This 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.

Animals↗

PubMed2006

Expression of transcription factor Yin Yang 1 in human osteosarcomas.

The transcription factor Yin Yang 1 (YY1) is known to be present in some human cancer cell lines and its expression correlates with immune-mediated apoptosis. By using Western blot analysis, we have shown that the YY1 protein is strongly expressed in human osteosarcoma cells and localised mainly in the nucleus. Moreover, by using immunohistochemistry and RT-PCR techniques, we have analysed the expression of YY1 protein in biopsies from human osteosarcomas. The YY1 protein was not detectable by immunohistochemistry in osteoid tissue. However, its expression was restricted to osteosarcoma tissues. These data were confirmed by densitometric analysis of RT-PCR for YY1 expression. Thus, YY1 gene activation appears to be an early event in the process of osteoblastic transformation and its detection may represent, together with the analysis of other established markers, a useful diagnostic tool in human osteosarcomas.

Adolescent↗

PubMed2006

Effects of a pomegranate fruit extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis.

BACKGROUND: Atherosclerosis is enhanced in arterial segments exposed to disturbed flow. Perturbed shear stress increases the expression of oxidation-sensitive responsive genes (such as ELK-1 and p-CREB). Polyphenolic antioxidants contained in the juice derived from the pomegranate contribute to the reduction of oxidative stress and atherogenesis during disturbed shear stress. AIM OF THE STUDY: To evaluate the effects of intervention with the Pomegranate Fruit Extract (PFE) rich in polyphones (punicalagin, which is a potent antioxidant) on ELK-1, p-CREB, and endothelial nitric oxide synthase (eNOS) expression induced by high shear stress in vitro and in vivo. RESULTS: At the doses used in the study, both the PFE and the regular pomegranate juice concentrate reduced the activation of ELK-1 and p-CREB and increased eNOS expression (which was decreased by perturbed shear stress) in cultured human endothelial cells and in atherosclerosis-prone areas of hypercholesterolemic mice. PFE and pomegranate juice increased cyclic GMP levels while there was no significant effect of both compounds on the conversion of L-arginine to L-citrulline. Administration of these compounds to hypercholesterolemic mice significantly reduced the progression of atherosclerosis and isoprostane levels and increased nitrates. This protective effect was relevant with PFE. Vasomotor reactivity was improved and EC(25) values in response to Ach and NONOate were significantly increased in treated mice in comparison to controls. CONCLUSION: This study indicates that the proatherogenic effects induced by perturbed shear stress can be also reversed by chronic administration of PFE.

Analysis of Variance↗

PubMed2006

Therapeutic effects of concurrent autologous bone marrow cell infusion and metabolic intervention in ischemia-induced angiogenesis in the hypercholesterolemic mouse hindlimb.

Lower-limb ischemia is a major health problem especially when associated to hypercholesterolemia. Because of the absence of effective treatment in the advanced stages of the disease, amputation is undertaken to alleviate unbearable symptoms. Since tissue ischemia and hypercholesterolemia are associated with an overwhelming generation of oxygen radicals, metabolic intervention with antioxidants and l-arginine can induce beneficial effects beyond those achieved by a novel therapeutic approach represented by the use of autologous bone marrow cells (BMCs). The protective effect of BMCs and vascular protection by metabolic cotreatment (1.0% vitamin E added to the chow, 0.05% vitamin C and 6% l-arginine added to the drinking water) were examined in ischemia-induced angiogenesis in the hypercholesterolemic mouse hindlimb. Intravenous BMC therapy improved blood flow and increased capillary densities. 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.

Animals↗

PubMed2006

Physical training and metabolic supplementation reduce spontaneous atherosclerotic plaque rupture and prolong survival in hypercholesterolemic mice.

Moderate physical exercise (PE) combined with metabolic treatment (MT) (antioxidants and l-arginine) are well known to reduce atherosclerotic lesion formation in hypercholesterolemic mice. However, the long-term beneficial effects on unstable atheroma remain poorly understood. We started early PE training in large groups of 6-week-old hypercholesterolemic mice (by graduated swimming) alone or in combination with nutritional supplementation (1.0% vitamin E added to the chow and 0.05% vitamin C and 6% l-arginine added to the drinking water). Inactive controls did not receive PE. The spontaneous development of atherosclerotic plaque rupture (associated with advanced atherosclerosis) and survival rates were evaluated. Moderate PE elicited an increase in plasma levels of nitric oxide. Early combined treatment with PE and MT in the hypercholesterolemic mice significantly reduced lesions (also detected noninvasively at 10 months) and spontaneous atherosclerotic plaque rupture and prolonged survival more effectively than each intervention alone. Thus, early concerted actions of MT and PE improve the natural history of atherosclerotic lesions and reduce the plaque instability in hypercholesterolemic mice.

Animals↗

PubMed2006

Nitric oxide and atherosclerosis: an update.

Nitric oxide (NO) is a molecule that has gained recognition as a crucial modulator of vascular disease. NO has a number of intracellular effects that lead to vasorelaxation, endothelial regeneration, inhibition of leukocyte chemotaxis, and platelet adhesion. Endothelium damage induced by atherosclerosis leads to the reduction in bioactivity of endothelial NO synthase (eNOS) with subsequent impaired release of NO together with a local enhanced degradation of NO by increased generation of reactive oxygen species with subsequent cascade of oxidation-sensitive mechanisms in the arterial wall. Many commonly used vasculoprotective agents have their therapeutic actions through the production of NO. L-Arginine, the precursor of NO, has demonstrated beneficial effects in atherosclerosis and disturbed shear stress. Finally, eNOS gene polymorphism might be an additional risk factor that may contribute to predict cardiovascular events. However, further studies are needed to understand the possible clinical implications of these correlations.

Animals↗

PubMed2006

Pomegranate juice reduces oxidized low-density lipoprotein downregulation of endothelial nitric oxide synthase in human coronary endothelial cells.

We examined the hypothesis that pomegranate juice (PJ) can revert the potent downregulation of the expression of endothelial nitric-oxide synthase (NOSIII) induced by oxidized low-density liporotein (oxLDL) in human coronary endothelial cells. Western blot and Northern blot analyses showed a significant decrease of NOSIII expression after a 24-h treatment with oxLDL. Accordingly, we observed a significant dose-dependent reduction in nitric oxide bioactivity represented by both basal and bradykinin-stimulated cellular cGMP accumulation. These phenomena were corrected significantly by the concomitant treatment with PJ. Our data suggest that PJ can exert beneficial effects on the evolution of clinical vascular complications, coronary heart disease, and atherogenesis in humans by enhancing the NOSIII bioactivity.

Beverages↗

PubMed2006

Role of oxidative stress in experimental sepsis and multisystem organ dysfunction.

Massive increase in radical species can lead to oxidative stress, promoting cell injury and death. This review focuses on experimental evidence of oxidative stress in critical illnesses, sepsis and multisystem organ dysfunction. Oxidative stress could negatively affect organ injury and thus overall survival of experimental models. Based on this experimental evidence, we could improve the rationale of supplementation of antioxidants alone or in combination with standard therapies aimed to reduce oxidative stress as novel adjunct treatment in critical care.

Animals↗

PubMed2005

The role of oxidative stress in adult critical care.

Oxidative stress defines an imbalance in production of oxidizing chemical species and their effective removal by protective antioxidants and scavenger enzymes. Evidence of massive oxidative stress is well established in adult critical illnesses characterized by tissue ischemia-reperfusion injury and by an intense systemic inflammatory response such as during sepsis and acute respiratory distress syndrome. Oxidative stress could exacerbate organ injury and thus overall clinical outcome. We searched MEDLINE databases (January 1966 to June 2005). For interventional studies, we accepted only randomized trials. Several small clinical trials have been performed in order to reduce oxidative stress by supplementation of antioxidants alone or in combination with standard therapies. These studies have reported controversial results. Newer large multicenter trials with antioxidant supplementation should be performed, considering administration at an early stage of illness and a wider population of critically ill patients.

Adult↗

PubMed2005

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

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.

Animals↗

PubMed2005

Glycoxidation of low-density lipoprotein promotes multiple apoptotic pathways and NFkappaB activation in human coronary cells.

Apoptosis of arterial cells induced by oxidized low-density lipoprotein (oxLDL) is thought to contribute to the progression of vascular dysfunction and atherogenesis. It is well established that diabetes mellitus is accompanied by both glycosylation and oxidation LDL, but the biological effects of these modified lipoproteins are poorly understood. We demonstrate here that glycosylated oxLDL (glc-oxLDL) promotes apoptotic signaling in human coronary smooth muscle cells. This was associated by a decrease of the antiapoptotic protein Bcl-2, an increase of the pro-apoptotic protein Bax, and activation of caspase 3. Glc-oxLDL also activated NFK: B and decreased IK: B, these effects were more pronounced than those achieved with oxLDL. Our study shows that glc-oxLDL influences a broad cascade of signaling transduction pathways, which may not only result in apoptosis, but also could affect NFkappaB in human coronary cells. This cascade of events may influence the evolution of atherogenesis and vascular complications in diabetic patients.

Apoptosis↗

PubMed2005

Beneficial effects of pomegranate juice on oxidation-sensitive genes and endothelial nitric oxide synthase activity at sites of perturbed shear stress.

Atherosclerosis is enhanced in arterial segments exposed to disturbed flow. Perturbed shear stress increases the expression of oxidation-sensitive responsive genes (such as ELK-1 and p-JUN) in the endothelium. Evidence suggests that polyphenolic antioxidants contained in the juice derived from the pomegranate can contribute to the reduction of oxidative stress and atherogenesis. The aim of the present study was to evaluate the effects of intervention with pomegranate juice (PJ) on oxidation-sensitive genes and endothelial NO synthase (eNOS) expression induced by high shear stress in vitro and in vivo. Cultured human coronary artery endothelial cells (EC) exposed to high shear stress in vitro and hypercholesterolemic mice were used in this study. PJ concentrate reduced the activation of redox-sensitive genes (ELK-1 and p-JUN) and increased eNOS expression (which was decreased by perturbed shear stress) in cultured EC and in atherosclerosis-prone areas of hypercholesterolemic mice. Moreover, oral administration of PJ to hypercholesterolemic mice at various stages of disease reduced significantly the progression of atherosclerosis. This experimental study indicates that the proatherogenic effects induced by perturbed shear stress can be reversed by chronic administration of PJ. This approach may have implications for the prevention or treatment of atherosclerosis and its clinical manifestations.

Analysis of Variance↗

PubMed2005

Animal models of hypertension: an overview.

Hypertension is a multifactorial disease involving complex interactions between genetic and environmental factors. Development of experimental models of hypertension allowed dissection and isolation of various factors associated with regulation of blood pressure, inheritance of hypertensive traits, and cellular responses to injury. The phenotype-driven approach is taking advantage of selective breeding of animals (primarily rats) that exhibit a desired phenotype, like the useful SHR. Genotype-driven models include transgenic techniques, in which mice are the most successful for selective deletion or overexpression of target genes. Notably, a combination of comparative genomics strategies and phenotypic correlates enhances the utility of hypertension models and their clinical relevance. Indeed, experimental models enabled development of targeted interventions aimed at decreasing not only blood pressure but also target organ injury. Continued utilization of experimental models simulating human hypertension, particularly those that combine other clinically relevant comorbidities like obesity or hypercholesterolemia, may afford development of effective strategies to address this common disease. Nevertheless, a cautious approach is mandatory when experimental findings in these models are extrapolated to human hypertension.

Animals↗

PubMed2005

New advances in microarrays: finding the genes causally involved in disease.

Much progress has been made in the technologies available to assess global alterations in mRNA levels in clinical research samples. Although such transcript profiling can provide a powerful research tool, the broad range of options can be bewildering for the inexperienced investigator, and more often than not the limitations and pitfalls of this approach are not fully appreciated. It is important to recognize that the major goal of transcript profiling experiments can be to identify novel therapeutic targets or delineate complex patterns of gene expression that provide a potentially pathognomonic phenotype. Microarrays are therefore potentially powerful tools to address the need for high-throughput analysis techniques, but a careful postanalysis follow-up and validation of microarray experiments will be needed soon (1). A projected decrease in cost and complexity may facilitate increased availability of this technology in the physician's office, and future applications may then allow tailoring of clinical diagnosis and targeted therapeutic strategies.

Arteriosclerosis↗

PubMed2005

[Childhood infection and endothelial dysfunction: a potential synergistic link in atherosclerosis].

The prodromal stage of atherosclerotic lesions is already formed during human fetal development. The presence of infections during childhood may increase synergistically the progression of atherogenesis. After delivery, especially those children exposed to severe maternal hypercholesterolemia should be followed up for the onset and development of acute and chronic infections and be included in clinical and noninvasive examinations of vascular function.

Atherosclerosis↗

PubMed2004

Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice.

The pathogenic mechanisms by which physical exercise influences atherosclerotic lesion formation remain poorly understood. Because vigorous physical training increases oxidative stress, this study tested the hypothesis that graduated and moderate physical exercise together with metabolic intervention (l-arginine and antioxidants) may contribute to increased vascular protection. Exercise training in mice was induced by graduated swimming. In hypercholesterolemic male mice on an atherogenic high-cholesterol diet, graduated and moderate exercise lowered plasma cholesterol and decreased atherosclerotic lesions compared with sedentary control mice. Antioxidants (1.0% vitamin E added to the chow and 0.05% vitamin C added to the drinking water) and l-arginine (6% in drinking water) supplementation to exercising hypercholesterolemic mice further and synergistically reduced atherosclerosis compared with untreated exercised mice. Arterial oxidation-specific epitopes and systemic oxidative stress were reduced by metabolic intervention. Graduated chronic exercise elicited an increase in production of nitric oxide through increased endothelial nitric oxide synthase expression and ameliorated scavenger activities. Thus, metabolic intervention with l-arginine and antioxidants together with graduated and moderate exercise training reduce atherosclerotic lesion formation.

Animals↗

PubMed2004

Antioxidant intervention attenuates myocardial neovascularization in hypercholesterolemia.

BACKGROUND: Hypercholesterolemia (HC) and atherosclerosis can elicit oxidative stress, coronary endothelial dysfunction, and myocardial ischemia, which may induce growth-factor expression and lead to myocardial neovascularization. We tested the hypothesis that chronic antioxidant intervention in HC would attenuate neovascularization and preserve the expression of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF). METHODS AND RESULTS: Three groups of pigs (n=6 each) were studied after 12 weeks of normal or 2% HC diet or HC+antioxidant supplementation (100 IU/kg vitamin E and 1 g vitamin C daily). Myocardial samples were scanned ex vivo with a novel 3D micro-CT scanner, and the spatial density and tortuosity of myocardial microvessels were determined in situ. VEGF mRNA, protein levels of VEGF and VEGF receptor-1, HIF-1alpha, nitrotyrosine, and superoxide dismutase (SOD) were determined in myocardial tissue. The HC and HC+antioxidant groups had similar increases in serum cholesterol levels. HC animals showed an increase in subendocardial spatial density of microvessels compared with normal (160.5+/-11.8 versus 95.3+/-8.2 vessels/cm2, P<0.05), which was normalized in HC+antioxidant (92.5+/-20.5 vessels/cm2, P<0.05 versus HC), as was arteriolar tortuosity. In addition, HC induced upregulation of VEGF, HIF-1alpha, and nitrotyrosine expression and decreased SOD expression and activity, all of which were preserved by antioxidant intervention. CONCLUSIONS: Changes in myocardial microvascular architecture invoked by HC are accompanied by increases in HIF-1alpha and VEGF expression and attenuated by antioxidant intervention. This underscores a role of increased oxidative stress in modulating myocardial microvascular architecture in early atherogenesis.

Animals↗

PubMed2004

Serum p53 antibodies in patients affected with ulcerative colitis.

During tumor progression, the accumulation in genetic alterations is a fundamental characteristic of malignant cells. p53 gene is frequently mutated in human tumor. Cellular accumulation of p53 protein can initiate an immune response with generation of circulating anti-p53 antibodies. Patients with ulcerative colitis have an increased risk of developing colorectal neoplasm and, among the different genes involved in carcinogenesis, p53 may play a key role. Sera and tissues from 97 patients (M = 53, F = 44) affected with ulcerative colitis (UC) were collected. Serum anti-p53 antibodies (p53Abs) were detected in duplicate with ELISA method. Serum p53Abs were detectable in 9.3% (9/97) of patients affected with UC. In these patients, the titer of p53Ab ranged between 3.1 and 14.9 U/mL (mean, 6.6 U/mL; SD, 4.64). Serum p53Abs were undetectable in control group. With an immunoluminometric assay for the quantitative determination of p53, we found 9/97 positive samples (> or = 0.69 mg/mg of total proteins). In contrast, the samples of the remaining 89 patients were found negative (< or = 0.30 mg/mg of total proteins). All patients that were positive for anti-p53 antibodies were also positive with p53 protein accumulation in the tissue of colonic biopsies. In UC, follow-up with colonoscopy has several advantages. The colonoscopy is not well accepted by patients, and poor patient observance has the potential to seriously devalue the technique as a screening tool, despite practical considerations of competence within endoscopy service. Serological detection of p53Abs by enzyme-linked immunosorbent assay (ELISA) is easy to perform, does not require tumor specimen, can be performed in a routine diagnostic procedure, may be used in clinical practice, and could facilitate physicians in patient monitoring. We suggest that serum p53Abs assessment, indirect marker for p53 gene mutations, and abnormally high p53 protein levels could be considered to have a potential for use as a complementary test to improve surveillance program performance.

Adolescent↗